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CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present application is a divisional of U.S. patent application Ser. No. 12/609,385, filed on Oct. 30, 2009, the disclosure of which is incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to an improved apparatus and method for filling the propellant chamber of an implantable pump. In particular, the present invention relates to an improved propellant bag or pillow for use in introducing propellant into the propellant chamber of an implantable pump, as well as methods of utilizing same.
[0003] Implantable pumps have been well known and widely utilized for many years. Typically, such devices are implanted into patients who require the delivery of active substances or medicaments to specific areas of their body. For instance, patients who are experiencing severe pain may require pain killers daily or multiple times per day. Absent the use of an implantable pump or the like, a patient of this type would be subjected to one or more painful injections of medication multiple times during the course of the day. In the case of pain associated with more remote areas of the body, such as the spine, these injections may be extremely difficult to administer and particularly painful for the patient. Moreover, attempting to treat conditions like these through oral or intravascular administration of medication often requires higher doses of medication that may cause severe side effects. Thus, it is widely recognized that utilizing an implantable pump may be beneficial to both the patient and the treating physician.
[0004] Many implantable pump designs have been proposed, including pumps employing mechanical means for and gas pressure driven propellant means for expelling fluids from the pump. The present invention is directly related to the latter. More particularly, the apparatus and methods taught in the present application are capable of being utilized with many different types of gas driven pumps, such as those shown in U.S. Pat. Nos. 4,969,873; 5,085,656; 5,336,194; 5,836,915; 5,722,957; 5,814,019; 5,766,150; and 6,730,060, as well as U.S. Patent Application Publication Nos. 2006/0259015, 2006/0259016, 2006/0271021, 2006/0271022, 2007/0005044, and 2007/0112328. The disclosures of each of the above-noted patents and patent applications are hereby incorporated by reference herein, and certain of these references may be referred to throughout the present application.
[0005] In general, gas driven implantable pumps, like each of the above-noted patents and patent applications, utilize an expandable propellant (e.g., an isobarically expanding gas) that acts upon a membrane to push medicament or other fluid from the pump. A common problem with such pumps, which have existed for some time, revolves around the filling of the propellant chamber with propellant. Above-noted U.S. Pat. No. 5,766,150 (“the '150 Patent”) discloses an apparatus and method for use in such a filling process. As is shown in FIG. 1 of the '150 Patent (reprinted as FIG. 1 of the present case), that patent teaches the use of a propellant pillow 13 , which is filled with a gas propellant and placed into a propellant chamber 7 of an implantable pump. The chamber is thereafter sealed. FIG. 2 shows pillow 13 in greater detail, in particular the fact that the pillow includes a propellant bag 15 and septum 17 affixed to the bag, which are not labeled as such in the '150 Patent. Because bag 15 consists of a material through which the propellant may diffuse (i.e., a permeable material), the gas slowly diffuses through the wall of the pillow and into chamber 7 . Thus, the use of pillow 13 allows time for the propellant chamber and the remainder of the pump to be assembled before the gas escapes therefrom.
[0006] During assembly of a pump utilizing the device and methods taught in the '150 Patent, the assembly steps first include punching bag 15 from an air padded foil or the like, evacuating it of all gases, and subsequently refilling it with a propellant. These steps generally involve the use of at least one cannula, needle, or syringe 19 that pierces self-sealing silicone septum 17 to both evacuate all gases and introduce propellant. After being filled, pillow 13 is then introduced into a pump that has been divided into propellant chamber 7 and a fluid/medicament storage chamber 6 . Subsequent to inserting pillow 13 into propellant chamber 7 of the pump, that chamber is sealed and evacuated of all gases. This allows the propellant to slowly permeate through the walls of bag 15 and into propellant chamber 7 . This method is generally applicable to any gas pressurized implantable pump, including the ones described in the various prior art references listed above. It has also been found that when a heat procedure is utilized to seal a propellant chamber like chamber 7 , bags like bag 15 are caused to erupt (with one or more holes), thereby causing the propellant to more quickly fill the chamber.
[0007] While the device and methods taught in the '150 Patent has been utilized for some time in filling implantable pumps such as those disclosed above, it is not without its drawbacks. For instance, the initial evacuation of and subsequent filling of propellant within pillow 15 sometimes results in the structure of the bag being damaged by the syringe(s) 19 . More particularly, evacuation of gas from bag 15 (i.e., creating a vacuum) causes the walls of the bag to collapse upon themselves and sometimes into contact with the point of the syringe(s). This may result in the walls being pierced, which thereby leads to a faster escape of the propellant from bag 15 than is desired. Thus, while the '150 Patent suggests placing the pillow within a sealed propellant chamber in approximately two minutes, this time period is significantly reduced when the bag walls are damaged. More often than not, this damage to pillow 13 results in less propellant ultimately being contained within the propellant chamber.
[0008] Therefore, there exists a need for an improved pillow for use in an improved method of filling the propellant chamber of an implantable pump.
SUMMARY OF THE INVENTION
[0009] A first aspect of the present invention is a pillow for use in filling a gas pressure driven implantable pump. In a preferred embodiment, the pillow preferably includes a propellant bag for containing a propellant, the bag being formed of permeable material facilitating release of the propellant therefrom. The pillow also preferably includes a self-sealing septum structure having a top surface, a bottom surface, and a septum opening extending from the bottom surface partially through the septum structure. The bottom surface of the septum structure is preferably affixed to the bag.
[0010] In other embodiments according to the above-described first aspect, the septum structure includes two separate septa. In such a case, a first septum may include the bottom surface and the septum opening and a second septum is solid and includes the top surface. Other embodiments may include a bag that is unitary. The bag may also include a bag opening aligned with the septum opening. With regard to this latter embodiment, the bag opening may be formed subsequent to affixation of the septum structure to the bag. Still further embodiments employ a bag constructed of polyolefins, such as polypropylene or polyethylene, and a septum structure constructed of silicone rubber.
[0011] A second aspect of the present invention is a process for filling of a propellant chamber of a gas pressure driven implantable pump with a propellant. One preferred embodiment of this second aspect includes the steps of providing a pump having a medicament chamber and a propellant chamber, providing a propellant pillow including a permeable propellant bag and a self-sealing septum structure having a top surface, a bottom surface, and a septum opening extending from the bottom surface partially through the septum structure, the bottom surface being affixed to the bag, filling the pillow with the propellant, wherein the filling step includes laterally inserting a syringe into the septum structure, inserting the pillow filled with the propellant in the propellant chamber, and closing the propellant chamber.
[0012] Other embodiments of this second aspect may further include the step of evacuating the propellant chamber of substantially all gases. The evacuating step may be performed after the inserting step. The method may also include the step of evacuating the pillow of substantially all gases. The evacuating step may be performed through the use of the syringe inserted into said septum opening. Still further, the septum structure may include a first septum including the bottom surface and the septum opening and a second septum including the top surface. In such a case, the method may also include the steps of affixing the first septum to the bag and affixing the second septum to the first septum, through the use of an adhesive or the like.
[0013] A third aspect of the present invention is another pillow for use in filling a gas pressure driven implantable pump. In accordance with one preferred embodiment of this third aspect, the pillow includes a propellant bag for containing a propellant, the bag being formed of permeable material facilitating release of the propellant therefrom. The pillow may also include a first septum including a septum opening and a second septum being of a solid construction. The first septum is preferably affixed to the bag and the second septum is preferably affixed to the first septum.
[0014] In other embodiments of this third aspect, the bag is unitary. Likewise, the bag may include a bag opening aligned with the septum opening. Such an opening may be formed subsequent to affixation of the septum structure to the bag.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] A more complete appreciation of the subject matter of the present invention and the various advantages thereof can be realized by reference to the following detailed description in which references made to the accompanying drawings in which:
[0016] FIG. 1 is a cross-sectional side view of a prior art propellant pillow disposed within a propellant chamber of an implantable pump.
[0017] FIG. 2 is an enlarged cross-sectional illustration of the propellant pillow shown in FIG. 1 with a needle inserted therein.
[0018] FIG. 3 is a perspective view of a propellant pillow in accordance with one embodiment of the present invention.
[0019] FIG. 4 is a cross-sectional side view of the propellant pillow shown in FIG. 3 .
[0020] FIG. 5 is a cross-sectional side view of a propellant bag portion of the propellant pillow shown in FIG. 3 prior to assembly with other portions of the pillow.
[0021] FIG. 6 is a cross-sectional side view of the propellant pillow of FIG. 3 with a first septum attached thereto.
[0022] FIG. 7 is a cross-sectional side view of the propellant pillow of FIG. 3 illustrating the introduction of propellant into the propellant bag.
[0023] FIG. 8 is a cross-sectional side view illustrating the placement of the propellant pillow shown in FIG. 3 between two flexible membranes of an implantable pump.
[0024] FIG. 9 is a cross-sectional side view of a fully assembled implantable pump with the propellant pillow of FIG. 3 placed within its propellant chamber.
DETAILED DESCRIPTION
[0025] In describing the preferred embodiments of the subject illustrated and to be described with respect to the drawings, specific terminology will be used for the sake of clarity. However, the invention is not intended to be limited to any specific terms used herein, and it is to be understood that each specific term includes all technical equivalents which operate in a similar manner to accomplish a similar purpose.
[0026] Referring to FIGS. 3 and 4 , there is shown an improved propellant pillow 20 in accordance with the present invention. As shown in that figure, as well as those figures that follow, pillow 20 includes a propellant bag 22 , a first septum 24 including an opening 26 , and a second septum 28 overlying the first septum. Although shown in the figures as being of a circular shape, propellant pillow 20 , as well as its components, may take on any shape suitable for use in placement in an implantable pump or the like.
[0027] Propellant bag 22 (shown by itself in FIG. 5 ) is preferably constructed of polyolefins, such as polypropylene or polyethylene, and, like in the '150 Patent, is punched out from a larger sheet of similar bags. While the material is discussed above as being polypropylene or polyethylene, any material suitable for containing a propellant utilized in an implantable pump and thereafter allowing such to permeate through its walls can be used. In its initial state, propellant bag 22 is a completely sealed enclosure, but as will be discussed more fully below, at least one opening 30 is created in the propellant bag.
[0028] Septa 24 and 28 are preferably created of silicone material, such as silicone rubber, but may be any material suitable for allowing resealing after the introduction of a needle therethrough. As is mentioned above, first or lower septum 24 is formed with opening 26 that allows for access to a portion of propellant bag 22 . Overlying septum 24 is second or upper septum 28 , which is a solid structure that not only overlies the first septum, but also opening 16 . As shown in FIG. 6 , first septum 24 is first affixed to propellant bag 22 , with, second septum 28 thereafter being affixed to the first septum. Both of the septa are preferably affixed utilizing glue or other adhesive, such as cyanacrylate. However, other means of attaching these components to the propellant bag and each other may be utilized.
[0029] After septa 24 and 28 are placed on propellant bag 22 , propellant pillow 20 is capable of being utilized to fill the propellant chamber of an implantable pump. Such a filling operation generally includes several steps. First, a syringe or other like device is inserted through septum 28 and opening 26 in first septum 24 , and into contact with the portion of propellant bag 22 that opening 26 overlies (not shown). The introduction of the syringe creates opening 30 in propellant bag 22 at this location. Once opening 20 in propellant bag 22 is created, the syringe or needle is withdrawn. However, it is also contemplated to provide a propellant bag 22 which initially includes this opening prior to the application of septa 24 and 28 thereto. This is in fact shown in FIG. 5 , and would negate the need for a separate opening forming step.
[0030] Second, the same or another needle or syringe 32 is inserted laterally through first septum 24 until the tip of the needle extends into opening 26 (best shown in FIG. 7 ). In this position, the needle can be utilized to evacuate all air or other gas that is contained within propellant bag 22 , such that the air or other gas exits through opening 30 of propellant bag 22 , into opening 26 of first septum 24 , and through the needle. Like in the prior art propellant pillows, this evacuation step generally results in propellant bag 22 collapsing upon itself. However, because of the design of the present propellant pillow, needle 32 is not permitted to engage any portion of propellant bag 22 during its collapse.
[0031] Once the air or other gas has been evacuated from propellant bag 22 , thereby creating a vacuum, the same laterally inserted syringe 32 , or a subsequently inserted syringe, can be utilized to infuse propellant bag 22 with propellant. Again, any propellant exiting syringe 32 goes through opening 26 in first septum 24 , through opening 30 of propellant bag 22 , and into the propellant bag. After this filling step is completed, syringe 32 may be removed from first septum 24 , which preferably self-seals because of its material. Propellant pillow 20 is now infused with gas that is only allowed to exit via a slow permeation through the material of propellant bag 22 . The propellant pillow may then be placed in the propellant chamber of an implantable pump, much like is discussed in the '150 Patent, and as is shown in FIGS. 8 and 9 of the present application. In particular, FIG. shows propellant pillow 20 placed between two flexible membranes of an implantable pump, while FIG. 9 shows the propellant pillow placed in a fully assembled implantable pump. It is to be understood that like in the context of the '150 Patent, the propellant chamber of the pump may be evacuated of all gas in order to create a vacuum. Further, this may be done before or after insertion of pillow 20 in the chamber. It is to be understood that other devices, like cannulas or needles, may be utilized in the foregoing steps.
[0032] It is contemplated that other designs for propellant pillow 20 may be employed. For instance, propellant bag 22 may, instead of being punched from a sheet of previously formed bags, be formed through the use of two membranes of like permeable material adjoined to one another. Likewise, it is contemplated that first and second septa 24 and 28 may in fact be integrally formed as a single septum. In this case, a lower surface of that single septum would include an opening corresponding to above-discussed opening 26 . Finally, it is to be understood that the various embodiment propellant pillows 20 discussed herein, as well as the methods of utilizing same, can be utilized in conjunction with many different implantable pumps. Certain examples are provided in the present application, but these are by no means meant to limit the use of the propellant pillow to such disclosed pumps.
[0033] Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims.
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An improved propellant pillow and method for filling a propellant chamber of an implantable pump with propellant through the use of such an improved propellant pillow are disclosed. The propellant pillow includes an improved design that prevents the damage of such during evacuating and filling procedures.
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[0001] This application is a continuation in part of application Ser. No. 11/478,322, filed on Jun. 29, 2006 and also claims priority on provisional patent application entitled Three Dimensional Imaging of Veins, Application No. 60/817,623, also filed on Jun. 29, 2006, all disclosures of which are hereby incorporated by reference.
FIELD OF INVENTION
[0002] The invention described herein relates generally to an imaging device, in particular, an imaging means for enhancing visualization of components covered by living tissue thin opaque films. More particularly, the present invention is directed to enhancing the visualization of veins, arteries and other subcutaneous structures of the body for inter alia facilitating fluid insertion into or extraction from the body or otherwise visualizing subcutaneous structures for diagnosis of the medical condition of a patient or administration of medical treatment to a patient.
BACKGROUND OF THE INVENTION
[0003] A visit to a doctor's office, a clinic or a hospital may necessitate vascular access that is, the insertion of a needle or catheter into a patient's vein or artery. These procedures may be required for many reasons including: to administer fluids, drugs or solutions, to obtain and monitor vital signs, to place long-term access devices, and to perform simple venipunctures. Vascular access ranks as the most commonly performed invasive medical procedure in the U.S—over 1.4 billion procedures annually—as well as the top patient complaint among clinical procedures. The overwhelming majority of vascular access procedures is performed without the aid of any visualization device and relies on what is observed through the patient's skin and by the clinician's ability to feel the vessel—basically educated guesswork.
[0004] Medical literature reports the following statistics: 28% first attempt IV failure rate in normal adults, 44% first attempt IV failure in pediatrics, 43% of pediatric IVs require three or more insertion attempts, 23% to 28% incidence of extravasations/infiltration, 12% outright failure rate in cancer patients, 25% of hospital in-patients beyond three days encounter difficult access. The miniature vein enhancer of the present invention may be used by a practitioner to locate a vein and is particularly useful when trying to locate a vein in the very old, very young or obese patients. More than fifty percent of attempts to find a vein in the elderly, who have a generally high percentage of loose, fatty tissue, and in children, who have a generally high percentage of small veins and “puppy fat”, are unsuccessful. The present invention is aimed at reducing and/or preventing the discomfort and delay associated with botched attempts to pierce veins for injections and blood tests. In addition, the present invention can cut the time it takes to set up potentially life-saving intravenous drip. During venous penetration, whether for an injection or drip, it is essential to stick a vein in exactly the right location. If a practitioner is only slightly off center, the needle will more than likely just roll off and require a re-stick.
[0005] Other Approaches
[0006] It is known in the art to use an apparatus to enhance the visual appearance of the veins in a patient to facilitate insertion of needles into the veins. An example of such a system is described in U.S. Pat. Nos. 5,969,754 and 6,556,858 incorporated herein by reference as well as a publication entitled “The Clinical Evaluation of Vein Contrast Enhancement”. Luminetx is currently marketing such a device under the name “Veinviewer Imaging System.”
[0007] The Luminetx Vein Contrast Enhancer (hereinafter referred to as LVCE) utilizes an infrared light source (generated by an array of LEDs) for flooding the region to be enhanced with infrared light. A CCD imager is then used to capture an image of the infrared light reflected off the patient. The resulting captured image is then projected by a visible light projector onto the patient in a position closely aligned with the image capture system. Given that the CCD imager and the image projector are both two dimensional, and do not occupy the same point in space, it is relatively difficult to design and build a system that closely aligns the captured image and the projected image.
[0008] A further characteristic of the LVCE is that both the imaging CCD and the projector have fixed focal lengths. Accordingly, the patient must be at a relatively fixed distance relative to the LVCE. This necessitates that the LVCE be positioned at a fixed distance from the region of the patient to be enhanced.
[0009] The combination of the size of the LVCE and the fixed focal arrangement precludes using the LVCE as small portable units that are hand held.
[0010] Other patents such as U.S. Pat. No. 6,230,046, issued to Crane et al., implement a light source for illuminating or trans-illuminating the corresponding portion of the body with light of selected wavelengths and a low-level light detector such as an image intensifier tube (including night vision goggles), a photomultiplier tube, photodiode or charge coupled device, for generating an image of the illuminated body portion, and optical filter(s) of selected spectral transmittance which can be located at the light source(s), detector, or both.
[0011] All citied references are incorporated herein by reference in their entireties. Citation of any reference is not an admission regarding any determination as to its availability as prior art to the claimed invention.
OBJECTS OF THE INVENTION
[0012] The present invention is directed to technologies and processes associated with the use of one or more moving laser light sources to detect the presence of blood-filled structures, such as venous or arterial structures, below the surface of the skin and to project an image back on to the skin that shows the operator the pattern of detected structures. The present approach uses one or more laser light sources that are scanned over the body using mirrors and a light detector that measures the reflections of the laser light and uses the pattern of reflections to identify the targeted blood rich structures. Various preferred approaches are described for the main subsystems of the design as well as various alternative techniques for accomplishing the objects of this invention.
BRIEF DESCRIPTION OF DRAWINGS
[0013] FIG. 1 shows preferred scan patters and the waveforms used to generate them
[0014] FIG. 2 shows mirror systems for folding and scanning the lasers
[0015] FIG. 3 shows the use of a dielectric mirror to combine multiple lasers into a coaxial output beam
[0016] FIG. 4 shows the use of a polarized mirror to combine multiple lasers into a coaxial output beam
[0017] FIG. 5 shows the use of an array of lasers to eliminate the need for a second moving mirror for scanning the lasers
[0018] FIG. 6 shows the use of a light valve element to eliminate the need for a second moving mirror for scanning the lasers
[0019] FIG. 7 shows the system and waveforms for detecting a vein and re-projecting an image along the same path.
[0020] FIG. 8 shows various methods for separating visible and infra red lasers from the reflected signal
[0021] FIG. 9 shows a focusing system for an LED
[0022] FIG. 10 shows a mechanical focusing mechanism for an LED embodiment of the invention
[0023] FIG. 11 shows an auto-focus system for a camera/projector based embodiment of the invention
[0024] FIG. 12 shows the waveform of the reflected signal
[0025] FIG. 13 shows an array of photo detectors arrange to increase the detection area in proportion to the angle from center
[0026] FIG. 14 shows the use of a short wavelength laser in combination with an infrared laser to eliminate the effect of the changing topology of the body as the laser scans across its surface
[0027] FIG. 15 shows a vein lock system that aids in the discrimination of veins from other structures.
[0028] FIG. 16 shows the preferred wavelengths for various elements in the system.
[0029] FIG. 17 shows a side view of a prototype embodiment of the invention.
[0030] FIG. 18 shows an alternate side view of a prototype embodiment of the invention.
[0031] FIG. 19 shows views of several sub assemblies of a prototype embodiment of the invention.
[0032] FIG. 20 shows a view of the prototype embodiment with parts removed so that the laser path and the key components controlling the laser path are visible.
[0033] FIG. 21 shows an alternative view of the prototype embodiment with parts removed so that the laser path and the key components controlling the laser path are visible.
[0034] FIG. 22 shows a view of the prototype embodiment with a circuit board removes so that additional elements are visible
[0035] FIG. 23 shows the enclosure of a prototype embodiment from a top-side view.
[0036] FIG. 24 shows the enclosure of a prototype embodiment with the scan head separated from the handle.
[0037] FIG. 25 shows the enclosure of a prototype embodiment from a side view.
[0038] FIG. 26 shows the enclosure of a prototype embodiment from the bottom.
[0039] FIG. 27 shows the enclosure of a prototype embodiment from with the top and bottom separated so that the internal assembly is visible.
[0040] FIG. 28 shows the top part of the enclosure of a prototype embodiment with the other parts removed.
[0041] FIG. 29 shows a block diagram of a prototype embodiment of the invention.
[0042] FIG. 30 shows a Fresnel lens assembly that can be used to enhance the return signal from the edges of the scan area.
SUMMARY OF THE INVENTION
[0043] Using One or More Lasers to Capture and Project an Image
[0044] Blood vessels, both venous and arterial, absorb red, near infrared and infrared (IR) light to a greater degree than surrounding tissues absorb those wavelengths of light. Therefore when illuminating the surface of the body with infrared light, blood rich tissues such as veins will absorb more of this light and other tissues will reflect more of this light. Analysis of this pattern of reflections enables the veins to be located. The present invention includes both a positive or negative image that is projected in the presence of a vein. Thus, a vein can be represented by a bright area and the absence of a vein can be presented as a dark area and vice versa.
[0045] A laser diode is preferred in the present invention as it emits light over a known, narrow wavelength range and when appropriately focused projects a small spot that varies very little in size over a wide range of distances. This is an effect that is commonly seen in laser pointers and laser gun sights.
1. In addition to a laser diode, the laser light used in the present invention can be generated by other laser light emitting elements including but not limited to VCSEL lasers, other semiconductor lasers and other solid state lasers. In the present invention a narrow wavelength of light is emitted producing a constant spot size even when the range to the target varies. The narrow wavelength allows a laser diode or diodes to be selected that have the desired characteristics of the ability to detect blood through differential absorption and the ability for a human eye to detect the reflected light. As will be discussed, certain embodiments may require differing tradeoffs in light wavelength. Additionally, the same characteristics of the laser that make it beneficial for detecting blood presence with useful resolution also makes it useful for projecting the pattern of blood and vein distribution back on to the skin. The major difference is laser selection for the projection application is to ensure that the wavelength of the light is within the visible spectrum for the human eye. For example, 635 nm light is perceived as bright red light by the human eye, while an IR laser at 740 mm is nearly invisible to the eye but is absorbed more by blood vessels than by surrounding tissues and can be measured using various photo detector technologies. Other colors of light such as green have significant benefits as the projected color since the eye is most sensitive to these wavelengths and it has a high contrast with many skin colors. Furthermore, in certain embodiments a single color laser may be selected that through novel techniques can perform both the projector and scanner functions. In this application, terms visible and infrared light are used to describe approximate wavelengths of light being used in the invention. Furthermore, specific wavelengths have been referenced in certain embodiments. These conventions were used for both clarity of discussion and as specific references to devices and wavelengths that are commercially available today. Referring to FIG. 16 , the useful spectrum for each of the critical functions in a detection system is shown. As new devices become commercially available with desirable characteristics they can be used in the invention as long as their wavelengths fall in or near the identified ranges for their particular function. For example, a 785 nm laser might be a preferred embodiment since it would be:
a. Lower cost since it is produced in high volumes for use in DVD players b. Available in higher power versions of 120 milliwatts and above c. Easier to separate from 638 nm since their wavelengths are further from each other d. Less divergent
[0051] Additionally, the use of laser as opposed to other techniques known in the art such as the Luminetx product allows finer control over the scanning for blood vessels. Since the laser is only striking a single spot on the body, the laser that is used to detect the presence of blood can be modulated on the fly wherein the intensity can be increased or decreased on a spot by spot basis. In a camera based solution, since the infrared light floods the area being scanned, no such control is possible.
[0000] Mirrors
[0052] Through the use of movable mirrors, the laser spot can be rapidly moved across the target area of the body. As the spot moves across the body there will be a modulation of the amplitude of the reflected light that is proportional to the attributes of that point on the body. For example, red, near IR and IR light will be absorbed and reflected in proportion to the amount of blood at the point at which the laser strikes the body. The invention uses this modulation to determine the location of veins. Other wavelengths of light will be reflected in proportion to the topology of the body at the point at which the laser strikes and can be used for enhancing vein detection.
[0000] Scan Mirrors
[0053] The invention uses one or more moving mirrors to move the laser light spot across the patient's skin in a variety of different possible patterns. The laser light is projected from a light generator on to the mirror and as the mirror is moved, the projected spot of light moves as a function of the angle of the mirrors at a given moment in time. The light is projected on to one or more mirrors moving in a coordinated way so as to generate a pattern of light on the target surface such as the patient's skin. Many patterns are possible by changing mirror attributes such as mirror size, position in relationship to each other and to the laser or lasers, the degree of the mirror's angle and the speed of mirror movement.
[0000] Random Vs. Fixed Patterns
[0054] A scanning method implemented with the present invention is unique in its approach to scanning the target area. In general, the lower the level of precision required in positioning the laser spot, the easier and less costly it is to produce the pattern.
[0000] Coaxial Lasers
[0055] In a preferred embodiment, instead of a laser projector there is no need for a reproducible scan pattern so that from frame to frame the laser scan lines do not need to fall reproducibly upon the scan lines of the prior frame, thus, there is no need to know the instantaneous position of the laser. The reason being, the light used for detection and for projection are either from the same light source or from multiple coaxially aligned light sources and the vein detection is performed in near real time. The projected visible light can be modulated in real time so that whatever location is being imaged is instantaneously being projected and only a small offset between detection and projection occurs which will not be noticeable to the user. Therefore, since the image projection happens within the scan, it doesn't matter if the scan pattern on the next traversal of the area proceeds in the same way the previous scan pattern did.
[0000] Parallel Lagging Projection Laser
[0056] If small additional processing time is required, rather than coaxially arranging the scan and projection lasers, the system can hold them parallel with a small gap in one direction. In this way, the spots follow closely behind each other as the mirrors move, but there is additional time between when the detection spot hits a point on the body and when the closely following projection spot hits the body.
[0000] Repeatable Patterns
[0057] In other embodiments, there are benefits to knowing the instantaneous position of the laser spot. In such embodiments, the desire would be to delay the projection of the image so that analysis that requires additional time can be performed.
[0058] A raster pattern is one type of repeatable pattern. In such a pattern, there are a number of different delay strategies.
1. A short time delay that is a subset of a scan line where the lasers are arranged in parallel rather than coaxially so that the projection spot lags slightly behind the detection spot. 2. Alternating scan lines where as the lasers pass right to left the system performs detection and as it passes from left to right it projects 3. Alternating frames where the lasers complete their full x and y travels while capturing the information into memory and then projecting on the subsequent frame.
[0062] These differing approaches each have benefits. The shorter the time delay between capture and projection, the less complicated the system needs to be in terms of processing and memory. As the delay increases, more information needs to be stored and processed, and hand jitter becomes more of an issue. If the frame rate is fast enough, the user would not notice the lag even with the occurrence of hand jitter. Hand jitter is the result of motion of the hand holding the scanner in relationship to the body. In typical systems with frame rates of 30-60 Hz one or two frame delay is practical. If additional frames are needed for processing, than the frame rate can be increased to minimize the delay. Alternatively, the system can use digital or optical image stabilization well known in the art to maintain alignment from frame to frame. One method would be to use accelerometers can be used to determine the amplitude and direction of the movement from frame to frame. Many other techniques are well known in the art.
[0063] The positive side of frame-level or multi-frame delay is that more complex algorithms can be used to identify the veins such as edge detection and line detection algorithms that are well know in the art.
[0000] Averaging Across Frames
[0064] One embodiment of a system that uses repeatable scanning is one in which the image is averaged across two or more frames, thereby increasing the quality of the image captured and therefore increases the ability of the system to accurately detect the position of blood vessels.
[0000] Pattern Generation
[0065] Many patterns of scanning are possible. For example, the patterns can be based on raster, collapsing ellipse, spirals, lissajous or random. Tradeoffs between pattern and system complexity can be made to create multiple products of differing cost and performance. For example, if the mirrors are run at their natural resonance frequency, the system minimizes the power needed to move the mirrors thereby either extending battery life or reducing the battery size needed and thereby reducing size, weight and cost.
DETAILED DESCRIPTION OF THE INVENTION
[0066] Referring to FIG. 1 a - 1 d , preferred embodiments are shown that generate raster, lissajous and collapsing ellipse and spiral patterns. The drawings show the mirror (e.g., 1250 ) on top of the electrical wave form (e.g., 1258 ) that is applied to the mirror to control its motion. These sinusoidal wave forms move the mirror in a back and forth pattern with maximum deflection at the peak of the wave, rest at the center of the wave and the opposite maximum deflection at the opposite peak of the wave. Also indicated in the drawing are the most preferred frequencies and the preferred ranges that would be used in an implementation of the invention.
[0000] Raster Pattern Generation
[0067] In FIG. 1 a , a raster pattern 1257 is generated using two mirrors. Mirror 1250 is mounted so that it has a single degree of freedom of motion at fulcrum 1251 / 1252 . A laser light source as described elsewhere strikes the mirror at an appropriate angle so that the angle of reflection is such that the light properly strikes the second mirror 1255 . Mirror 1250 oscillates at a high frequency, for example, such as 20 KHz 1258 . This generates the horizontal motion in the raster pattern 1257 . The now moving beam 1253 is projected on to the second mirror 1255 so that it is parallel to its axis of movement. Mirror 1255 is mounted so that it has a single degree of freedom of motion at fulcrum 1254 / 1256 . Mirror 1255 moves at a slower rate such as, for example, 60 Hz as shown in waveform 1259 . The generated pattern is bi-directional, with the beam moving right to left and left to right as the fast mirror 1250 moves and top to bottom and bottom to top as the slow mirror 1255 moves.
[0068] A preferred embodiment uses 20 KHz for waveform 1258 and 60 Hz for waveform 1259 . Other preferred embodiments can use 7 KHz to 35 KHz for waveform 1258 and 45 Hz to 90 Hz for waveform 1259 .
[0000] Lissajous Pattern Generation
[0069] Referring to FIG. 1 b , a preferred embodiment for the generation of a lissajous pattern 1265 using a single mirror 1272 that can move on two axes is shown. An alternative embodiment would be to use two mirrors arranged as shown in FIG. 1 a but modulated as described for the lissajous pattern. The mirror is capable of moving along the axes created by fulcrum pairs 1266 / 1269 and 1267 / 1268 . The mirrors are moved at different frequencies and in a specific phase relationship to generate this pattern. A lissajous pattern is mathematically described by the equations:
X=A sin( at +phase), Y=B sin( bt )
The two axes are modulated based on this relationship where various values of A, B and the phase offset control the specifics and density of the projected lissajous pattern. Waveform 1270 shows the X value over time and waveform 1271 shows the Y value over time. In the equation, A is the amplitude of waveform 1270 and B is the amplitude of waveform 1271 . at and bt are the angle of the sine waves over time and phase is the phase shift (angle offset) between the two waveforms 1270 / 1271 . Many values of these variables can be used for a scanning application, but a preferred embodiment would select values that move the mirror at its resonant frequencies so as to minimize power consumption.
[0070] A preferred embodiment uses 400 Hz for waveform 1270 and 60 Hz for waveform 1271 . Other preferred embodiments can use 300 KHz to 35 KHz for waveform 1270 and 45 Hz to 90 Hz for waveform 1271 .
[0000] Collapsing Ellipse Pattern Generation
[0071] In FIG. 11 c , the system is configured for a collapsing ellipse pattern 1286 where a series of loops are drawn across the target area with each circle either slightly smaller or slightly larger than the previously drawn circle. Again, a single mirror 1287 is shown, but the same function can be performed with two moving mirrors. The mirror is capable of moving along the axes created by fulcrum pairs 1282 / 1284 and 1285 / 1283 . The mirrors are moved at identical frequencies and are 90 degrees out of phase to generate this pattern. The X direction of mirror movement is controlled by the waveform 1280 . The Y direction of mirror movement is controlled by the waveform 1281 . This waveform 1281 is amplitude modulated so that each subsequent full wave is slightly changed in amplitude so that a different sized circle is drawn.
[0072] A preferred embodiment uses 8 KHz for waveform 1280 and 8 KHz for waveform 1281 . Other preferred embodiments can use 7 KHz to 35 KHz for waveform 1280 and 7 KHz to 35 KHz for waveform 1281 .
[0000] Spiral Pattern Generation
[0073] The spiral pattern 1290 in FIG. 1 d is shown generated by a single mirror 1297 but could be drawn with two mirrors as previously shown. The mirror is capable of moving along the axes created by fulcrum pairs 1291 / 1293 and 1292 / 1294 . The mirrors are moved at identical frequencies and are 90 degrees out of phase to generate this pattern. The X direction of mirror movement is controlled by the waveform 1295 . The Y direction of mirror movement is controlled by the waveform 1296 . Both waveforms 1295 / 1296 are amplitude modulated in a sawtooth pattern generating a spiral pattern.
[0074] A preferred embodiment uses 8 KHz for waveform 1295 and 8 KHz for waveform 1296 . Other preferred embodiments can use 7 KHz to 35 KHz for waveform 1295 and 7 KHz to 35 KHz for waveform 1296 .
[0000] Bounce Mirrors
[0075] In addition to moving mirrors, one or more fixed mirrors may be used in the design of the invention. This allows many different arrangements of the light sources to minimize overall size or to otherwise optimize the positioning of the components of the device.
[0076] Referring to FIG. 2 a , the laser source 10 is oriented to emit light 13 in a desired direction. A mirror 11 is placed in the path of the laser light at an angle to the light beam that is calculated to bounce the light beam 14 into the new desired direction. Additional mirrors 12 can be placed in the path of the beam to further redirect the light beam 15 into a desired orientation. Although two mirrors are shown in FIG. 2 a , as many or as few mirrors as required can be used. Additionally, although FIG. 2 a is drawn in two dimensions and the angles shown are right angles; these angles can be set so that the beam is reoriented at any angle required in three dimensions.
[0077] In FIG. 2 b , the laser source 20 is oriented so that the beam 21 strikes the mirror 22 at the appropriate angle and position. Mirror 22 is a moving mirror with an axis of motion shown at 24 . In FIG. 2 b , the mirror is presented as moving on a single axis and therefore projects a single line on the target surface. Mirrors with two degrees of freedom are well known in the art and mirror 22 can be replaced by such a mirror so that it projects a two dimensional scan and projection field on the target area. Alternatively, a second moving mirror can be used as will be described in FIG. 2 d.
[0078] Note that the laser beam 21 can be redirected by one or more bounce mirrors as shown in FIG. 2 b if necessary to the specific embodiment. Such an implementation is shown in FIG. 2 c . Laser source 30 projects a beam of light 31 so as to strike the mirror at the desired position and angle. Mirror 32 is oriented so that the reflected beam 33 strikes the appropriate position on the moving mirror 34 . Again, the for ease of drawing, mirror 34 is shown moving on a single axis 35 , but can be replaced by a mirror with two degrees of freedom so as to project and scan a two dimensional area with only a single mirror.
[0079] FIG. 2 d shows a two mirror system that is used to project and image a two dimensional area. The laser source 50 is oriented so that the beam 51 strikes the mirror 52 at the appropriate angle and position. Intermediate bounce mirrors could be placed in the beam path 51 to reorient the beam. Mirror 52 is a moving mirror with an axis of motion shown at 53 . The now moving beam of light 54 is directed to moving mirror 55 . Mirror 55 has an axis of motion 56 that is oriented at an angle such as 90 degrees from the axis of motion of mirror 52 shown at 53 . In this manner, the light reflected off of mirror 56 forms a two dimensionally shaped scanning pattern 59 on the target area 58 .
[0080] Different embodiments will use one or more laser colors and sources to perform detection and projection. One embodiment of the invention uses two lasers to perform its functions where one laser is selected to have optimum performance at blood detection (e.g., 740 nm) and the second laser has optimum characteristics to project the resulting image to the user (e.g., 638 nm). The major benefits of this embodiment include the ability to modulate the detection and visible lasers simultaneously, and the ability to select lasers that have ideal characteristics for the function to be performed (rather than a trade off between detection and visibility as will be seen in a single laser embodiment). The laser sources (e.g., FIG. 2 d , 10 ), can be an assembly that provides one or more colors of laser light either arranged either coaxially side by side in parallel.
[0000] Combining Lasers with Polarization or Dielectric Mirror
[0081] A key element of this embodiment is a mirror system that in addition to moving the light spot as previously described provides a mechanism that causes the two laser beams to become coaxial so that both lasers strike the same point on the patients skin. There are many different ways to align co-axially the visible laser and the infrared laser including the use of dielectric mirrors.
[0000] Combining Lasers with Dielectric Mirrors
[0082] Dielectric mirrors are specially coated mirrors that can reflect selected wavelengths (or wavelength ranges) of light while allowing other wavelengths to pass through the mirror. In this embodiment one or more coated mirrors are used in the optical path to make the separate laser sources coaxial so that when they strike the moving mirror subsystem, they then strike the same spot on the skin.
[0083] Furthermore, separate control systems are provided to modulate the intensities of the lasers. The laser intensities can be independently modulated to control the desired characteristics such as depth of detection and the brightness of the projected image providing a great degree of control over these desirable characteristics.
[0084] Additional embodiments are possible where additional lasers are added to provide for further refinement of the detection and presentation of the detected blood. For example an additional laser could be used to determine range to the surface of the skin so that finer control over the depth of detection can be performed. Another example is the use of a second color of visible light so that additional information about useful attributes such as depth of the blood vessel can be presented to the user.
[0085] FIG. 3 depicts a dielectric mirror approach. The mirror is shown with the infrared laser placed behind the dielectric mirror. The dielectric mirror is selected so that the infrared laser (e.g., 740 nm) passes through the mirror. The back side of the mirror can be coated with an anti-reflective coating 106 to minimize loss of intensity of the infrared light due to reflection from the back surface of the mirror. It also minimizes the shielding necessary for the back reflection of the infrared light. Note that there is a refraction effect on the infrared laser that is adjusted for by the proper alignment of the lasers. The visible laser (e.g., 638 nm) is directed to the front surface of the mirror which is coated with a material that reflects the light of that laser. The combination of the transmitted laser light and the reflected laser light is now aligned and exits the assembly coaxially. Various implementations can be created that alternate the positions of the visible and infrared lasers.
[0086] Similar assemblies can be repeated multiple times for creating coaxial combinations of more than two lasers if needed for the specific marketing or technical requirements of the product.
[0000] Combining Lasers with Polarized Elements
[0087] A characteristic of laser light is that it is polarized in a known orientation. By carefully controlling the orientation of the laser light, dielectric elements that reflect and pass light polarized in specific orientations can be used to coaxially align the lasers.
[0088] With regard to the polarized approach, referring to FIG. 3 and replacing the dielectric coated mirror with a polarized element as shown in FIG. 4 . One laser is polarized in a first orientation and is placed behind the polarized element. The polarized element is selected so that the first polarized orientation passes through but the second polarized angle is reflected. The second laser is polarized to the second polarized angle and is aimed at the front of the polarized element and is angled and aimed so that the reflection of the first laser is coaxial with the second laser passing through the polarized element.
[0089] In FIG. 4 , the element 110 is shown with the infrared laser 111 placed behind the polarizing element. The laser 111 polarization (orientation) and the polarizer 113 orientation is selected so that the infrared laser 111 passes through the element. The back side of the element can be coated with an anti-reflective coating 116 to minimize loss of intensity of the infrared light due to reflection from the back surface of the element. It also minimizes the shielding necessary for the back reflection of the infrared light. Note that there is a refraction effect on the infrared laser 115 that is adjusted for by the proper alignment of the lasers. The visible laser 112 is directed to the front surface of the element 113 polarized so that it is reflected by the element. The combination of the transmitted laser light and the reflected laser light is now aligned and exits the assembly coaxially. While element 110 shows a coating on the front surface, the coating may also be placed on the opposite surface.
[0090] Similar assemblies can be repeated multiple times for creating coaxial combinations of more than two lasers if needed for the specific marketing or technical requirements of the product. Additionally, the visible and infrared lasers may be swapped if desired and the parameters of the assembly adjusted appropriately.
[0000] Multiple Lasers in a Single Package
[0091] Laser diodes that combine more than one laser into a single package can also be used as the laser light source. This eliminates the need for additional beam combining elements in the system. For example, Sanyo DL-1195-251 provides both a red and an infrared laser in a single package.
[0000] Multiple Source Array for 1d Scanning
[0092] All the embodiments so far have related to a visible laser point source and a IR laser point source bouncing off multiple mirrors, or a single mirror moving in multiple directions, to create a two-dimensional scanning pattern where both the X and Y axis of the two dimensional imaging area is scanned with the single coaxial source of laser light. Rapid scanning causes the eye to integrate this into a single image. In such a system, the beams need to be actively steered in both the x and y directions in the desired pattern. Since there is only reflection from the point at which the laser is currently striking, the photo detector sub system can make inferences about the presence of veins at that particular spot on the target.
[0093] An alternative embodiment would be to use a linear array of visible laser sources and a linear array of IR laser sources which then are reflected off a single mirror moving on a single axis. The effect of putting these lasers side by side is to eliminate the need to move the laser point in both the X and Y directions. An appropriate density of laser sources will be required so that the image presented to the user achieves a desirable resolution. These sources could be from individual lasers for each desired line of resolution or from a lower resolution array optically split into a sufficient number of sources to achieve the desired resolution. Many laser arrays known in the art could be used including a VCSEL array.
[0094] Using a laser array, you “paint” an entire field of view with the broad brush (the array of laser sources). An advantage of this approach is (i), the mirrors are less complex, and (ii) that the collection of the reflected IR light could also be by means of a retro collective mirror. A retro collective mirror has a field of view corresponding to the array of lasers, and moves in concert with the movement of the array of lasers. A retro collective unit has a significantly improved signal to noise ratio since it is only receiving signal input at any given time directly in a line of sight with the lasers, thereby minimizing the effect of ambient light and other noise sources. A retro collective mirror is inherently larger than a mirror that simply moves the beam. This is to allow for a large light collection area. However due to inertia, as the mirror is made larger, it can no longer be moved as fast as needed for a single laser. This arrangement of multiple lasers allows the system to eliminate the fast moving mirror.
[0095] As shown in FIG. 5 a , the array of laser light sources 400 / 408 / 403 , is arranged so that the beams strike the moving mirror 402 / 406 / 402 perpendicular to the axis of rotation 402 a / 407 so that as the mirror swings back and forth on its axis, the laser beams are scanned so that the emitted light forms a rectangle on the target surface 410 . FIG. 5 b shows a side view of the arrangement, with the array of lasers 403 strike the moving mirror 402 and are reflected in a moving pattern 404 .
[0096] In addition to the paired visible and IR lasers, the array of lasers could be a single wavelength array of sources that use one wavelength to detect and project as described elsewhere.
[0097] In addition to lasers, if the distance to the object being scanned is tightly controlled, then LEDs could be used in place of lasers.
[0000] Using Light Valves
[0098] A device called a grating light valve, such as those made by Silicon Light Machines (http://www.siliconlight.com), can be used in a similar manner to an array of laser sources. These light valves, typically based on MEMS technology, are basically mirrors that can be set to a reflective or non reflective state. They are typically packaged as an array of light valves 1506 as shown in FIG. 6 .
[0099] Referring to FIG. 6 , a light source 1500 generates a laser beam 1501 which is caused to strike a diffraction grating 1502 which spreads the beam into a line. Since this line of light is divergent 1503 , lens 1504 is used to refocus the light 1506 onto the grating light valve 1506 . The light 1508 , with only a single element reflected from the grating light valve shown for clarity, is reflected off the grating light valve and is directed to a moving mirror 1509 , which moves along its axis 1510 , and is then modulated in the second axis by that moving mirror and is projected 1511 to the target area. By enabling a single light valve to reflect and all the rest to absorb in synchrony with the movement of mirror 1509 , a single scan line can be painted on the target area. Two or more of the assemblies in FIG. 6 can be bundled together so that one or more assemblies are used for visible light and one for infrared light, or a single assembly can be used for both projection and detection as will be described below.
[0100] This embodiment can also be combined with a retro collective mirror system to enhance the collection of the reflected light.
[0000] Single Laser
[0101] In another embodiment, the invention uses a single laser that emits light at a wavelength that is long enough that it is still differentially absorbed by blood but is still visible to the human eye. This embodiment is very important in that it enables building a system with only a single laser. All the complexity associated with aligning multiple lasers is eliminated thereby greatly reducing cost, engine size, unit size and power consumption.
[0102] Light emitted at 635 nm is one possible choice. In this embodiment, the laser spot performs the dual function of detecting the presence of blood and displaying that presence of blood to the user. It has been determined that a portion of a 635 nm laser penetrates into the tissue and is absorbed by the veins. Accordingly the 635 nm laser can functions as did the infrared lasers for the purpose of imaging the veins. A portion of the 635 nm light does not penetrate the skin and is reflected off of the skin so that it is visible to the user. This portion of the light functions as did the visible laser in the dual laser system.
[0000] Single Laser Always on
[0103] A novel mechanism is used to allow the single laser to be used for both functions. In this embodiment the laser is never completely turned off. Accordingly, even when the image to be displayed is black, the laser is still powered on at a very low level. The low level is strong enough that it can still be detected by the photo detectors so that the device can still image the veins, but not strong enough to create a distracting visible image (so blacks may appear as a faint red color). When the intensity of the 635 nm laser is subsequently increased to project a bright portion of the visible image, the gain of the analog circuitry associated with the received signal (from the photo detectors) is reduced in proportion. Conversely, when the intensity of the 635 nm laser is subsequently decreased to project a darker portion of the visible image, the gain of the analog circuitry associated with the received signal is increased accordingly. In this manner, the received signal (as measured after the analog circuitry) remains relatively constant regardless of the intensity of the projected image.
[0104] Referring to FIG. 7 a , a single laser source 70 is oriented so that its beam 71 is aimed into a steering assembly 72 . This assembly is constructed as described elsewhere in this patent out of a series of fixed and moving mirrors as appropriate to the specific embodiment. A moving light beam 73 is emitted from the device which then scans the targeted area of the body 74 in a pattern that is appropriate to the specific embodiment.
[0105] Typically in this configuration, neither repeatability nor knowledge of the specific beam position at a given time is required since the processing is done in real time as the light beam reads and paints the skin. However, the delay techniques that were discussed previously can be applied to a single laser configuration.
[0106] The photo detector 76 is positioned to measure the light 75 reflected from the skin. Since this is a scanning point source, the reflected light is an instantaneous representation of the reflection from a single point 82 on the body. Note that the beam penetrates some distance into the body so the reflected signal is a composite of both surface and subsurface features. The output of the photo detector 77 is fed into a detection circuit 78 [that uses techniques that are well known in the art] to determine a change in the amplitude of reflected light and therefore detecting the relative amount of blood at the point 82 at which the laser is currently scanning.
[0107] The detection circuit 78 provides an output 79 to the power supply 80 to the laser source 70 . As soon as a vein is detected at the point 82 , the power is increased to the laser source 70 which increases the output of the laser so that it is visible to the operator. As soon as the detection circuit 78 detects that the point 82 is no longer over a vein, then the control output 79 is changed so that the laser 70 outputs a light level that is sufficient for detection, but is no longer visible, or is dimly visible, to the operator. The detection circuitry includes the functionality to cancel out the increased reflection when the laser is brightened and the decreased reflection when the laser is dimmed so that the action of projecting the image does not interfere with the ability to detect the veins.
[0108] If desired, the sense of on and off can be inverted, whereby the laser is brightly lit when no vein is detected and dim when a vein is detected.
[0109] FIG. 7 b provides a representation of the signals being used by the system. The reflected signal 90 - 94 is representative of what is seen at the inputs 75 and outputs 77 of the photo detector as well as the initial stages of the detection circuitry 78 . The corrected signal 95 , 96 represents what would be seen in later stages of the detection circuitry 78 once the variations in the laser amplitude 88 , 89 are canceled out. The detected vein 97 , 98 are representative of the logic in later stages of the detection circuitry 78 as well as the output signal 79 from the detection circuitry 78 to the input of the laser power supply 80 . The laser output amplitude 88 , 89 represent the output of the laser source 70 , 71 as it is increased and decreased to project the acquired image.
[0110] Following the reflected signal, at 90 the system is seeing a varying analog signal that is representative of a reflection pattern indicative of a beam that is not crossing a vein. Since different individuals based on skin color, skin condition and place on the body will reflect different amounts of light as this baseline 90 , the detection circuitry is designed so that it can determine this baseline in real time. At 91 , there is an amplitude drop off as the beam crosses a part of the body where blood is absorbing sufficient light that the detection circuit 78 determines that the beam is over a vein. An internal representation or flag 97 that the beam is over a vein is set and the output to the laser power supply 79 is changed so that the laser amplitude is increased 89 to the bright condition thereby projecting the vein position. Once the beam is brightened, there is a corresponding rise in the amplitude of the reflected light 92 . Internally, the detection circuit 78 corrects for that amplitude 96 to eliminate false readings and to prevent saturation of the detection chain 76 , 77 , 79 .
[0111] As the beam 73 continues to move, as long as the reflected level continues within the range for vein presence 92 , the laser will stay in its high state 89 . The beam will eventually move off of the vein and the reflection will increase once again 93 indicating that the beam has moved off of the vein. The detection circuitry 78 will then cause the laser power supply 80 to return to the dim state 88 . The reflected signal will now be reduced 94, the detected vein flag will be turned off 98 . This process will continue to repeat for the duration of scanning.
[0000] Single Laser PWM
[0112] It is desirable in some embodiments to have greater control over the intensity of the beam when it is being used for detection. In a single laser system, it is required that the beam intensity be low enough in the dark areas of the image so that they appear clearly different from the lit areas. It would be desirable in certain circumstances such as different skin coloration or the desire to scan more deeply below the skin to bring the intensity of the light up for scanning. In this embodiment, the modulation of the laser between detection and projection can be in real time where the invention time slices the laser between detection and projection so that both functions are performed on the same pass of the laser over the skin.
[0113] In FIG. 8 a such a modulation scheme is shown. The signal 1350 shows the sample period for the photo detector. When the clock is high 1352 , the signal is sampled. When the clock is low 1351 , the signal from the photo detector is ignored. The laser output is switched between bright 1354 and dim 1359 . Dim can also be off in some embodiments. As the beam passes over the body, the beam is kept at a bright intensity 1355 until a vein is detected during the period at 1360 . In this example, the vein is seen across two periods 1353 . In these periods, the output beam is dimmed 1356 / 1357 for the portion of the time period that is not used for sampling at the photo detector. It is brought back to its bright level 1361 during the sample period of the photo detector. Many variations of this scheme are possible including working with multiple lasers of different colors, and changing the timing of the detection 1352 and projection 1351 intervals and allowing for multiple levels of bright 1354 and dim 1356 .
[0114] In addition to modulation between detection and presentation modes as described, the laser can also be modulated within each of these domains to provide for variable detection characteristics such as changing the depth of penetration and detection through the skin and changing the intensity of the projection intensity to allow for variations in user preference, ambient lighting conditions and skin color.
[0115] Another embodiment of the single laser approach is to time slice the laser output so that very short pulses of high intensity are emitted followed by longer periods of projection intensity. Projection intensity is the light output level that the system wishes the user to see. Vein detection occurs at the bright pulses, but since they are very short, and the eye has a slow response time, they will not perceptibly interfere with the desired projection image. The advantage of this embodiment is that it allows higher intensity for the detection phase allowing for deeper structures to be imaged and allows the system to adjust for skin characteristics.
[0000] Alternating Line & Alternating Frame
[0116] The techniques discussed previously for alternating lines and frames between detection and presentation in a multiple laser system can also be applied in a single laser system.
[0117] The use of these delay techniques allows all of the advanced vein detection techniques to be applied by allowing extra time between detection and projection as previously discussed as well as the improvements yielded by the additional control of laser intensity provided.
[0000] Using LEDs Instead of Lasers
[0118] As previously discussed a major benefit of lasers was that the beam remains a constant size over a very wide range of distances between the light source and the surface of the patient's body. An alternative embodiment can be created that is of lower cost which uses tightly focused light emitting diodes (LEDs).
[0119] In FIG. 9 , a focusing scheme is shown for an LED light source. The LED 150 projects an unfocused beam of light 151 on a lens or assembly of lenses 152 which are designed to have a specific focal length so that the converging light 153 comes to a point 154 at a useful working distance. Beyond the working distance the light begins to diverge 155 .
[0120] The disadvantage is that the distance between the scanner and the body surface will need to be much more tightly controlled than in a laser embodiment. Several controlling mechanisms are possible such as a physical device that is placed against the skin. One possible mechanism is shown in FIG. 10 a . This approach uses a mechanical device that includes an open base 424 that is placed against the skin while allowing the image to be captured and projected through the opening 425 . The opening can be either closed as shown or open based on the design requirements of the specific embodiment. The base 424 is connected to the scan head 422 through one or more separation members 423 / 424 that are sized to ensure the proper distance is maintained between the scan head and the skin. The scan head 422 can be fixed to the positioning device or it can be a separate piece that is attached when needed and then removed.
[0121] In an alternate construction, as shown in FIG. 10 b , the mechanism can simply be a rod 430 of the appropriate length that projects from the scan head so that the distance is maintained when the end of the bar touches the skin 420 .
[0122] Additional features include:
1. A lighted crosshair or other pattern projected towards the skin that becomes crisply focused when the device is being held at the proper range 2. An electronic ranging mechanism such as infrared or ultrasonic that measures the distance and then emits a set of tones that indicates that the device is at the appropriate distance. The tone feedback can be positive—only on when at the proper distance, negative—only on when outside of the proper distance or both with separate tones to indicate the two states.
[0125] IR Camera, LED Projector
[0126] Another useful embodiment of the invention is based on the use of LED projection with alternative types of detection. Given the need for tight control to be maintained of working distance, or to provide an auto focus mechanism in an LED embodiment, the detection subsystem can be replaced with a camera element that is sensitive to IR light and an IR light source to illuminate the target area. In this embodiment, the image would be captured using the camera, processed to detect vein positions within the field of view and an LED implementation as described earlier would be used to project the image back on the patient's body.
[0000] Auto-Focusing in Non-Laser Embodiments
[0127] As discussed, a key benefit of using lasers is that they are inherently focused over a wide working range. As discussed above, since LED's do not remain focused over a long working range, the use of LEDs requires tight control of distance to the body area to be imaged. Auto-focus lenses, such as those seen on cameras, could be integrated into the design so that a broader working range can be provided. Typically however an LED implementation is used to minimize cost so that normally the expense of auto-focusing would have limited application. However, other embodiments of vein enhancement systems such as that described in U.S. Pat. Nos. 5,969,754 and 6,556,858 would benefit from the use of auto-focus technology and have a cost basis that support such an implementation. FIG. 11 shows an improvement to the device shown in FIG. 1 from U.S. Pat. No. 5,969,754. In this figure, an auto-focusing feature has been added. Computer controllable focusing lenses 1200 , 1201 , 1202 are placed in front of the key optical systems, typically replacing the existing lenses (e.g. 14). These controllable auto-focus lens systems are controlled by either the main computing element of the system or a separate microprocessor dedicated to control functions such as and including auto focus. Distance to the body is determined by a range detection system 1203 , many different types which are well known in the art.
[0000] Photo Detector
[0128] In addition to the subsystems that project the laser or laser spots on to the patient's skin, a further subsystem provides the detection of the light that is reflected from both the skin and the subsurface features of the patient's body. As previously mentioned, blood rich areas of the body such as veins absorb light in the infrared spectrum to a greater degree than surrounding tissues. The invention uses one or more photo detectors to measure the varying amount of reflection from the target. Light sensitive devices including photo diodes, CCD camera elements and CMOS camera elements and LEDs can be used as the photo detector to perform these measurements. The present invention can implement multiple photo detectors spatially separated so as to increase sensitivity, and reduce the interference associated with speckle, and specular reflection. However, as mentioned previously, one can achieve a reasonable result by using a single photo diode; this will depend on the desired output and/or operating needs.
[0129] The characteristics of the photo detector(s) will vary between embodiments. Photo detectors can be selected with narrow band characteristics so that only the detection laser is received by the detector. This would also have the advantage of making the system less sensitive to ambient light. Detector characteristics can be determined through selection of the photo detector itself or through the use of filter materials placed in front of the detector. Another alternative approach would be to use a photo detector that is sensitive to a broad range of wavelengths and then by modulating the transmitted laser light, the system would be able to determine which laser, and therefore light wavelength, was being detected at a given moment in time.
[0000] Variations on the Number of Photo Detectors Used
[0130] Different embodiments may use different numbers of photo detectors based on the technical and business needs of the specific implementation. For example, a single photo detector might be used to minimize size or cost. Multiple photo detectors may be implemented so that they are spatially separated so that the system is less sensitive to specular reflection. Skin is somewhat shiny and causes unwanted specular reflection. In an embodiment where the photo detectors are separated, they each see the returned signal from a slightly different angle so that the effect of specular reflection is minimized.
[0131] The larger the area of a photo diode (one type of photo detector) the lower the speckle noise seen by the system since the random pattern of speckles are integrated as a single reflection since they all strike the photo detector simultaneously. The larger area means that the small speckles are a smaller percentage of the total area and therefore have less of an impact on the signal. However, larger photo diodes have more capacitance and are therefore slower, which is undesirable in many embodiments of the invention. By using multiple photo diodes, the detector area is increased, providing the reduction in speckle noise, without the negative impact on the speed of the detector. This is due to the smaller capacitance of the smaller photo diode and the fact that each photo diode being able to have its own pre-amplifier circuit.
[0132] A further benefit of having multiple photo diodes is that the received signal is increased without the need for additional amplifier gain and the associated noise that it would introduce into the system.
[0133] A further benefit of having multiple photo diodes is that as the laser point moves across the human limb, the curvature of the limb causes an increasing amount of the light to be reflected away from the scanner as the beam moves to the sides of the limb. The addition of spatially separated photo detectors adds additional collection area nearer to the spot being scanned and allows more of the reflected light to be captured. In addition, having two separately placed photo detectors reduces the impact of specular reflection.
[0134] As an alternative to the addition of a photo detector, collection mirrors can be used in the collection path so that light is collected from spatially separate points and are then reflected on to a single photo detector shared by two or more collection mirrors.
[0135] FIG. 12 shows an oscilloscope image of the signal received from the photo detectors. The large ‘humps’ 1700 are caused primarily by the change in angle as the laser scans across the arm. The amplitude of these humps will be affected by the angle at which the beam strikes the arm. A vein signal is also shown 1701 .
[0000] Array of Photo Diodes
[0136] In one embodiment, there is an array of smaller photo detectors arranged so that there is more collection area towards the outside of the detection area (where the roll off of signal due to the curved body and the angle of the laser occurs) and less towards the center where the reflection is more direct and intense. An example pattern is shown in FIG. 13 . This could be implemented as a discrete photo detectors arranged in the appropriate pattern or as a monolithic semiconductor component.
[0000] Fresnel Lenses—Tailored Response Over the Field of View
[0137] Another technique to control the variation of reflection due to the change in laser angle across a scan line is to use specially configured lenses over the photo diodes. In this example a lens is cut from a standard fresnel lens in a pattern that increases the amount of collected light as the angle from the center of the photo diode increases thereby flattening the received signal.
[0138] As shown in FIG. 30 , a standard fresnel lens 1750 is cut in a pattern 1751 that when placed over the photo detector provides additional collection of light reflected from the edges of the scan line and then refracts that light into the photo detector.
[0000] Electronic Filter
[0139] The frequency domain of the signal caused by the angle change as the laser sweeps is slightly different than the signal caused by the presence of a vein. Through the use of electronic filters, well known in the art, such as switched cap filters, the impact of this signal can be reduced early in the signal processing chain, importantly prior to the vein detection circuitry.
[0000] Measuring Topology with an Additional Laser
[0140] In the prior descriptions, a simplified model of the reflection of the laser light was presented. In fact, there are varying degrees of absorption of light from all of the structures illuminated including the skin, the blood vessels and other surface and subsurface structures of the body. Additionally, since the body is a three dimensional structure, the range to the point on the surface being scanned varies in real time as the imaging point is scanned. For example, the curved shape of the arm would result in less returned reflection towards the edge of the arm as that surface curves away from the scanning device. The result is that these variable reflections off of these body structures add signals that must be filtered out to accurately detect the vein structure. Furthermore, as the beam sweeps across the body, when the beam is at the center point of its sweep, the reflected light received at the photo detector is greater than when the angle of the beam is at its maximum deflection and therefore more light is reflected away from the photo detector.
[0141] There many techniques that can be used to eliminate or cancel out these undesirable signals.
[0142] The reflected signal received by the infrared photo detector is representative of both the veins and the surface topology of the patient's body. Put another way, the surface of the patient affects the reflected infrared signal. This is not desirable in that in most applications the user is only interested in the veins of the patient and not the surface topology. It has been observed that the short wavelength light such as blue and ultraviolet are reflected by the skin and is mainly representative of the surface topology of the patient and has no vein information contained therein. By utilizing a second coaxial laser light source at a short but visible wavelength and a second photo detector subsystem for receiving the short wavelength light reflected signal, the short wavelength light signal (which contains information about the topology of the skin) can be subtracted from the infrared signal (topology+veins) yielding a signal that is solely the veins (topology+veins−topology=veins). This works in that since the beams are coaxial, they will be affected by the topology of the target area symmetrically.
[0143] This approach is particularly useful in a system that does not have a microcomputer for storing a complete image and for performing image processing on that image to enhance the veins (and reject all other types of signals) but also has benefit to a stored image system.
[0144] Referencing FIG. 14 , the coaxial combination of the short wavelength and infrared laser 528 is projected on to the body surface. Reflected light 530 is captured by the photo detectors 526 and 527 . Detector 526 detects short wavelength light and detector 527 detects infrared light. These detection characteristics may be either a result of one of the signal modulation techniques described elsewhere herein, component selection or through the use of a filter 536 , 537 placed in the path of the reflected light.
[0145] The output of the photo detectors 526 , 527 are amplified and conditioned by pre amplifier circuits 631 , 632 and then fed through the differential amplifier 534 which subtracts out the surface topology represented by the reflected short wavelength light yielding an output 535 that is primarily based on the reflected vein pattern.
[0146] The simplest embodiment would use a red laser for both detection and projection as described earlier in conjunction with the short wavelength laser.
[0000] An Implementation with Three Lasers
[0147] As a further embodiment, a three laser system can be built to further enhance the captured and projected image. In this embodiment, three lasers are used: ultraviolet (e.g., 407 nm for imaging the skin topology), visible (e.g., 630 nm providing the visible light for image projection), and infrared (e.g. 740 nm for imaging the veins). Two photo detectors are used. One is for receiving the ultraviolet, and one is for receiving the infrared light. The ultraviolet laser has absolutely no penetrating qualities into the skin and therefore the reflection very faithfully reflects the patient's topology. This signal is then subtracted from the infrared signal to yield just the vein signal. This embodiment is further advantaged in that the wavelengths of the ultraviolet and infrared lasers are very far apart from each other, and therefore, there is no inadvertent signal pickup by the respective photo detectors.
[0148] This implementation would operate in a substantially similar way to what was previously described for FIG. 14 with the exception that the coaxial laser light source 528 would include three laser inputs: infrared for vein detection, ultraviolet for topology detection and a visible color for projection. Photo detector 526 would be selected for ultraviolet detection characteristics and/or filtered by 536 to provide selective detection of the ultraviolet laser.
[0149] Many combinations of multiple lasers and detectors are possible that each provide optimizations based on the type and depth of structure being scanned for, for example adding additional visible lasers for additional projected information as described elsewhere.
[0000] Long Pass Photo Detector Filter, Photo Detector Sees Only IR Light
[0150] One goal of the photo detector design is to acquire only the desired signal such as the vein pattern without interference from the reflected light from other objects in view such as the topology of the body or ambient light.
[0151] Many techniques are possible. In some embodiments, a photo detector will be selected that is matched to the wavelength of the infrared laser. In another embodiment, a filter that has the ability to block all light other than the wavelength of the infrared laser can be placed in front of the photo detector so that only the infrared light passes into the photo detector. In a third embodiment, the amplitude of the laser light is modulated either in the time or frequency domain, thereby allowing the system to know which laser is being seen by the photodetectors. The third embodiment has the benefit of allowing a photo detector that is capable of detecting a broad spectrum of light (e.g., a photo detector that is responsive to both 638 nm laser and 740 nm lasers). This allows a broader range of photo detector devices to be used that are selected for other desirable characteristics such as low cost, small size or greater sensitivity.
[0000] Special Laser Handling
[0152] As a mirror moves back and forth as it scans the laser beam it decelerates before it reaches a full stop then reverses direction and accelerates again. During some portion of the outer extremes of travel the mirror is moving too slowly for the information returned by the reflected laser to be used. In addition, the output power at these extremes is more dangerous because it is spread over a smaller area. Therefore reducing or blocking laser power in these extremes helps to ensure that it stays within government mandated safety limits. Furthermore, the laser current needed is proportional to the temperature of the laser. This is important in a battery powered device in that the amount of current needed to run a cooler laser is lower and therefore the battery lasts longer.
[0153] In the preferred embodiment, one or more of the lasers are turned off during the unused portion at the ends of the scan lines. The benefits of this are:
1. It saves power in the areas that are blind or unusable because of the slow movement of the mirror 2. It reduces overall power used by the laser since it is now off a percentage of the time, reducing the temperature of the laser 3. It extends battery life 4. It is safer, due to less power during the slow moving portion of the scan 5. The active area appears brighter since there is no bright edge to the pattern caused by the slow moving mirror
[0159] An alternative embodiment would leave the laser on all the time, but change the size of the exit window aperture so that the brighter parts of the scan are clipped off by the window. This embodiment is safer than the preferred embodiment in that the failure mode is less likely to occur, but there is none of the power savings. There are useful benefits to the internal reflection cause by clipping the output however. These include:
1. An internal photodiode can measure the reflected laser light for calibrating the lasers 2. In the case of projecting an image stored in memory, convergence (the need to know exact laser spot position between frames) becomes critical. If the laser beam can hit an extra photodiode when it touches the shade, then that signal can be used for laser spot position sync. If the shade is also mirrored, then the extra photodiode can be placed on the top PC board, to catch the reflected beam.
[0162] A further embodiment would be to proportionally reduce the power at the mirror slows so that the brightness is kept constant. This would be useful if a border demarking the edge of the image was desired or if some system data was to be displayed in this border area.
[0000] Safety
[0163] In some embodiments, it is desirable to maximize the output of the laser so that a greater signal or greater penetration into the body is needed. All laser projection devices have governmental safety agency regulations dictating power output limitations. These limitations are typically expressed as a maximum output of the laser at a given distance from the eye over some period of time. Therefore, a number of techniques that control power output and the time profile of the output can be used to ensure that the device meets these safety criteria.
[0164] The balance between high power (yielding brighter images or greater 3 d penetration) and safety are an important part of the design of the device.
[0165] In one possible embodiment, physical barriers can be placed in the design of the product that prevents the user's eye from getting close to the origin of the laser projections. If a user's eye can not get close to the source of the laser, the laser power may be increased. For example, in an embodiment, protruding bars (think of a football helmet cage) can be placed in the direction of the optical path that prevents the user from placing an eye too close to the lasers. Accordingly, the laser power can be increased.
[0166] In an alternative approach, signal processing can be utilized to control the power output. By way of example, veins have a very distinctive pattern, (e.g., they are tubular shaped). An embodiment can be created in which the acquired image pattern is stored in a computer memory, image processed to determine whether veins are present, and only upon confirmation of vein being present is the image projected. In this manner, the visible laser is not turned on if the unit is aimed at a user's eye (no vein pattern detected).
[0167] In a further embodiment, the power of the infrared laser can be set initially low to detect the presence of surface veins, and only after they are detected is the power of the infrared laser increased (to image deeper veins) and the visible laser turned on to project the vein pattern.
[0168] An additional alternative method is to only turn on the device a when a proximity sensor determines the surface, or eye of a user, is a predetermined distance away from the origin of the lasers, for example an Agilent HSDL-9100 proximity detector. The power of the laser can be set so that it is safe at the threshold distance. There are many range detectors known in the art such based on optical and ultrasonic techniques that can be used in the invention.
[0169] An additional alternative method is to turn the lasers on for a short duration to determine if a vein pattern is in view before turning the lasers on for an extended period to image the vein pattern.
[0170] Since the moving mirrors are subject to inertia, they will move more slowly towards the end of their movement than they do at the center of movement. Therefore, the laser intensity over time is higher at the edges than it is in the middle. The system can be designed to manage the bright edges as follows:
1. In some embodiments, it may be desirable to have the brighter edges since that helps demark the edge of the scan area 2. The housing can be designed so that the exit window clips (or blocks) the edges of the pattern so the more intense light does not exit the device 3. The electronics can be designed so that the amplitude of the transmitted laser is reduced near the edges 4. The electronics can be designed so that the laser is turned off near the edges
[0175] In all of these embodiments, these techniques can be applied to one or more of the lasers in the system. Furthermore they can be done independently, for example, the visible laser is left on to show the border line, while the IR laser is shut off at the edges.
[0000] Ergonomics
[0176] The basic invention provides for the detection of and the projection of an image of the pattern of blood vessels directly on to the patient's body. In this manner, the practitioner has a direct sense of where the veins are and where the center line of the vein is so that they may easily and accurately perform venipuncture. One intention of the invention is to be as easy to use as possible. One expression of ease of use is to ensure that the device enhances and doesn't interfere with the normal work process of finding and accessing the vein.
[0177] The integration of the detector and projector into a single device also improves on the Crane Patent. In Crane, the vein enhancer implements two separate devices, one for illumination and/or trans illumination and a separate device used for detecting the low light. Such a configuration is awkward and difficult to operate. In addition, having two separate devices increases the likelihood losing one of them.
[0000] Scanning Activation Techniques
[0178] Several techniques can be applied to allow the user to control operating characteristics of the device such as on/off and gain. This user input is very important from both a safety and operational standpoint. The gain of the scanning system will need to be changed based on skin color and condition as well as the depth of detection desired by the operator. The gain of the projection will also need to be adjusted based on ambient light conditions and skin color and condition.
[0179] These include
1. A trigger or switch mounted on the handle of the device in proximity to the normal position of one of the fingers such as the thumb. Such an implementation will be described later.
a. A trigger or switch that has one position used for on and off b. A trigger or switch that has two positions, where the first position puts the device into an aiming mode and the second begins scanning. This type of implementation could be useful in an LED or camera implementation where focal length is limited. c. A trigger or switch that has two positions, where the first position is for low gain, and therefore short penetration, and the second is for high gain. d. A trigger or switch with a single position that can be tapped multiple times to change the gain of the system
2. A slide switch trigger, where multiple positions along its travel change settings on the device 3. An analog trigger as in a video game joy stick, where the distance of the pull on the trigger is used to change settings of the device 4. A pressure sensitive switch where pressure is used to change settings on the device 5. A rolling thumb control where rolling the wheel in one direction reduces gain and the other direction increases gain 6. Any of the above implemented such that the switch stays in position when it is released and must be manually reset to an off position 7. Any of the above implemented as a dead man switch such that as soon as pressure is removed from the switch it returns to the off position.
Gravity Tilt for Aiming Projection on Skin.
[0191] In the present invention there are described a number of novel mechanisms to automatically maintain the position of the imaged area as the practitioner moves the needle to perform venipuncture. It will be appreciated by those skilled in the art that the present invention is not limited to locating veins, arteries and other blood-rich structures and either implicitly or explicitly focused on placing a needle into the structure. There are many procedures, such as an intramuscular injection, where it is desirable not to puncture a vein. The invention can be used to avoid hitting a vein in this case.
[0000] Gravity Adjusted
[0192] One such mechanism is to mount the imaging head on pivot-able mechanism mounted to the needle protector. The mechanism is arranged so that the force of gravity biases the projection angle at a predetermined angle to the earth's surface. As the needle is moved, the field of view continues to remain at a constant angle to the surface of the earth.
[0000] Computer Control Using Orientation Detection
[0193] Another mechanism would be to use electronic devices including tilt switches and/or accelerometers to monitor movement of the scanning element. A mechanism such as a switch press could be used by the practitioner to indicate that the scanner should go into a mode where it attempts to maintain the field of view on a fixed position on the body. As movement is detected, the device moves the scan area to compensate for the practitioners hand movement.
[0194] Several movement control mechanisms are possible. In one embodiment, positioning actuators can move the scan element in two dimensions thereby moving the imaging/projection area. In another embodiment, the internal mirror arrangement can be such that a bias is added or subtracted from the mirror's travel, thereby changing where the projected image is placed. In another embodiment, a combination of both techniques can be used. In another embodiment, an engine with higher than necessary resolution for vein location can be used and a window is moved within the higher resolution space.
[0000] Computer Control Using Feature Detection
[0195] The previous embodiment relies on the system detecting a change in its position by measuring the movement of the scan head. In another embodiment, as the image of the vein structure is captured, the system can identify unique patterns in the structure of the captured image. For example, the system could look at a cross point between two veins. In a frame to frame comparison, the change in position within the imaging field of this unique pattern can be determined and then the scan position can be moved by one of the techniques previously described so that the unique pattern is kept in a constant position within the imaging field of view.
[0000] Florescent Cream on Skin
[0196] In the embodiments previously described, the projection of the image relies on repeated scanning of a visible light source over the area of the body being scanned. It is known in the art that there are materials that emit visible light when energized by a violet or ultraviolet light source. These materials can continue to emit light for a period of time, up to several minutes, after the energizing light source is removed. Furthermore, these materials can be mixed into a gel, cream or liquid base so that it can be applied to the surface of the skin. In addition, the florescent material can be combined with the antiseptic that is already used in venipuncture.
[0197] An embodiment of the invention can be made where a violet or ultra violet laser (e.g., 407 nm) can replace the 630 nm laser. The practitioner can apply the florescent material to the surface of the skin and then the scanner can be passed over the area to scan the veins. The device uses the violet/UV laser to activate a pattern that matches the vein position on the treated skin.
[0198] This embodiment is very useful and unique for several reasons. First, the image of the vein position is maintained even after the device is turned off and put away, thereby freeing both hands for the venipuncture. Secondly, the size of the imaged area is now limited by the area that the florescent material is applied to, not by the projection area of the device. Third, if the procedure is taking too long, the image can be reactivated by rescanning the area.
[0199] Still further, a three laser system can be built, comprising a visible laser for presenting the vein image and a near IR for detecting the position of the veins and a violet/ultra violet for energizing the florescent materials. All lasers are arranged to project along a single axis. Without the violet/ultra violet laser turned on the system operates as described in previous embodiments. However, once an acceptable image is viewed, the 407 nm can be energized to paint the same image as that projected by the 630 nm laser, thereby energizing the florescent material to emit the vein image.
[0200] It is known in the art that there are chemical dyes that can change color by exposure to light. Such a material can be substituted in the above embodiments in place of a florescent material.
[0000] Distance Aware User Interface
[0201] Several control mechanisms that can be used to adjust various operating parameters for the unit are previously described. Another embodiment is to use sensors well known in the art to determine distance to the body surface being scanned. For example, an IRDA module typically used in a laptop computer could be used to sense distance by using the amount of reflection from the IR led back to the photo sensor as a proxy for distance.
[0202] These can be added to the device or in a preferred embodiment, the average intensity of one or more of the lasers already in the device can be used to approximate the distance based on the amount of light reflected. This average intensity would vary based on distance.
[0203] When the scanner is close, say 6″, the scanning angle can be set to maximum and the IR power, signal gain and differentiation levels are set to medium. As the scanner moves away from the body, the scanning angle can be reduced in proportion to the distance. In this way, if the target were for example the arm, the scanned area would not grow as distance increases. This would prevent wasting detection area by preventing the imaged area from growing bigger than the arm.
[0204] When unit is moved closer than 6″, the level of differentiation, and gain is increased. This is OK to do at close range but at far distances this would cause more false positives—veins would be indicated in places that they do not exist. However, at close range this will show deeper veins. This provides a very intuitive user experience. Move closer—see deeper. Other inventions that use fixed focal length systems and therefore must be kept at a single distance from the body cannot provide this user interface.
[0000] Electronics
[0000] Time Division Multiplexing Two or More Lasers
[0205] In the system design, the photo detector can be selected or filtered so that it is responsive to the infrared laser but not the visible laser. In the manner both lasers can be on at the same time without having the visible laser couple into the photo detector. In some cases, useful attributes of a photo detector such as size or cost would make it preferable to use a photo detector which is responsive to both the visible laser and the infrared laser. In this embodiment, both of the lasers can be pulsed on and off at high rates without affecting the apparent quality of the image (visible light projection) or the quality of the acquired image (the reflections of the IR laser). By synchronizing the two lasers so that while one is on, the other is off, the image acquisition circuits (photo diode and amplifiers) can be arranged to only see signals from the appropriate laser. In this manner the other lasers do not interfere at all with the signal acquisition apparatus.
[0000] Frequency Modulation of Lasers
[0206] Through the use of amplitude modulation on the transmitted laser, simple filter circuits can be used in the photo detection subsystem to allow one or more laser signals to be differentiated from ambient light and from other laser signals in the system. In FIG. 8 , the laser output signal waveform is shown with two levels, bright 1370 and dim 1372 . For example, in a single laser system, the bright signal might be used to project and the dim signal would be used to scan. Furthermore, the dim could also be an off state for the laser and this implementation would still be effective.
[0207] In the photo detector subsystem, the output of the photo detector can be DC coupled so that no low frequency or DC bias signals pass through to the next stage in the circuit. In this manner, any light, including ambient light, that doesn't exhibit the high frequency modulation, is not seen by subsequent stages of the circuit.
[0208] Another mechanism to differentiate between lasers is shown in FIG. m 1 c . In this embodiment, the lasers are amplitude modulated at different frequencies causing the reflected light received at the photo detector to also be frequency modulated. The visible laser 1380 is modulated at one frequency and the infrared laser 1383 is modulated at another. The light received at photo detector 1381 is a combination of the reflected light from both lasers. The received signal is fed through two different band pass filter circuits. The circuit at 1382 selects for one frequency and the circuit at 1385 selects for the other. Therefore the signal at 1384 and 1386 are representative only of the light reflection from one of the lasers. This can be implemented in a single circuit so that only the infrared vein signal is seen or in two or more circuits where both an infrared vein signal is seen and a long wavelength topology-detection signal is received. A whole range of high pass, low pass, band pass, band block and notch filters can be used based on the technical and business needs of the specific embodiment.
[0000] User Adjustments
[0209] The system can be arranged as either a binary system or grayscale system. In a grayscale system, the infrared laser signal received by the photo detector is simply echoed and re-transmitted by the visible laser. In this manner, various levels of intensity can be shown. Accordingly, the image of a vein may vary in intensity as a function of the magnitude of signal received.
[0210] In a binary system, the projected image is either on or off. To determine whether the projected image should be on or off, a comparator with a trip point is placed after the photodiode. If the signal crosses the trip point the visible laser is turned on and when it falls below the trip point it is turned off.
[0211] The system can set these parameters automatically based on built-in rule sets or a user input device like a dial, or push buttons, or any other means of user input could be placed on the device, and the user manually adjusts the trip point (essentially making the device more or less sensitive.)
[0212] Some of the parameters that will often need to be controlled to deal with patient and environmental variability include:
1. Laser intensity
a. Visible for projection brightness b. Infrared for penetration depth
2. Persistence of vein lock 3. Selection of vein size to detect 4. Working range and focus distance 5. Field of view size 6. Mirror amplitude
IR Modulation Analog or PWM (Pulse Width Modulation)
[0221] Throughout all the embodiments, when we discuss adjusting the power of a laser, such adjustment could be made by either adjusting the current to the laser, or alternatively, modulating the laser on and off at a rapid rate (pulse width modulation or PWM). Depending upon the duty cycle, the average laser intensity will be changed. With respect to the visible laser, the human eye integrates the signal and, provided the frequency of the PWM is faster than the eye integration time, the laser will appear as if it was always on, but brighter or dimmer as the on cycle time increases respectively.
[0222] The system will also need to adjust the power of the infrared laser. This can be done by adjusting the current to the laser, or alternatively, by PWM. Provided that the PWM modulation is faster than the response time of the receiving means (photodiode plus amplifiers), the modulation will have the same effect upon the received signal as if you reduced the current to the laser.
[0000] Simplified Scanning
[0223] There are various methods that can be employed for creating a scanned laser pattern. In many embodiments, it is desirable for the scan pattern to be the same from frame to frame and for the system to be able to determine the instantaneous position of the lasers. Such an implementation would allow time consuming processing and integration of data across frames to occur.
[0224] In general however, the lower level of position precision that is required, the easier it is to produce the pattern, the lower the system complexity becomes and the lower the cost becomes. In an embodiment without image memory, since one does not need to remember the specific signal at a specific position over time, there is no need for a reproducible scan pattern. Therefore, from frame to frame the laser scan lines do not need to fall reproducibly upon the scan lines of the prior frame and there is no need to know the instantaneous position of the laser. The reason one does not need a reproducible scan pattern or instantaneous position information is that the visible light is coaxially aligned to the infrared laser. The visible light is a function of the received image in real time. Accordingly, whatever location is being imaged is instantaneously being projected.
[0000] Scan Amplitude Modulation Scanning
[0225] One such simplified modulation scanner which is well suited to this invention is amplitude modulated circular mirror. In this case a mirror is arranged to run at resonance in a circular or oval pattern. The magnitude of the circle is then amplitude modulated at a rate high enough to avoid appearance of flicker. Accordingly, a scan pattern is formed which starts with small concentric circles and grows sequentially larger until reaching a limit and then collapses sequentially to the smallest circle.
[0226] Such a pattern has many advantages over a traditional raster scan pattern. Rather than a rectangular shape which would be typical of a raster scan, this method can be used to generate circular or oval pattern shapes. The mirror in this design is always moving and the laser is always actively painting—there are no required off times as the mirrors move into position for the next scan line. The pattern can be adjusted so that it spends more time scanning near the center of the pattern so a brighter, denser, better defined image appears in the center of the scan area. Additionally, the mirror operates at resonance which provides the lowest power dissipation, which is important in handheld battery operated devices.
[0000] System Gain Adjustment
[0227] It is necessary to adjust the gain of the system during operation in order to ensure that the amount of reflected light is within the proper operating range of the photo detectors.
[0228] One method of adjusting the gain is to maintain a constant output from the detection laser and adjust the gain of the photo diode amplification circuitry so as to get an appropriate signal that is neither too low for detection nor too high so that the photo detector or circuit saturates. This approach can become fairly complex due to the speed requirements of the gain adjustment.
[0229] Another method is to fix the gain of the photo detection circuitry but adjust the power output of the IR laser so that an appropriate signal is output from the photo detection circuitry (once again not to low or saturated). It is much easier to design circuits that adjust the IR laser due to the extremely high modulation bandwidth of the lasers. As previously discussed, the laser can be adjusted either by analog or digital means.
[0230] A laser must be calibrated in that its intensity is sensitive to ambient conditions such as temperature. Some laser diodes have internal mirrors to perform the calibration. An alternative technique is to use the housing of the scanner to block a portion of the light, perhaps an outer scan line and reflect that light back to the photo detector. That reflected light can be used for calibration.
[0000] Stored Image, Allows Multi-Scan Averaging
[0231] In some embodiments of the invention, the system will have a microprocessor and memory buffer so that the reflected light from the scanning laser will be kept as a representation in memory. By averaging the image over multiple scans, the system can form an image with greater resolution than it could have by only using a single pass of the laser. In order for this to be done, the system needs to ensure that the image elements being captured from scan to scan represent the same physical location on the patient.
[0232] The benefit to the system design is that the gain of the photo detector and subsequent analog circuits can be reduced.
[0233] There are several ways to do this. One is to provide a mechanical stabilization, similar to what was described for the LED implementation ( FIG. 10 ). Many techniques for mechanical, analog and digital image stabilization are known in the art and can be applied to this invention such as best fit correlation.
[0234] For example, you can identify a specific point or a group of points within the image in a single frame, for example the cross point between two veins. The system can then adjust the position of the image from frame to frame so that the image elements averaged together represent the same position on the body.
[0000] Windowed Vein Tracking
[0235] Since veins are linear structures, a novel technique can be used to accurately identify veins and to separately highlight one or more veins and ignore others without using image memory or signal processing techniques. Referring to FIG. 15 , a schematic representation of an arm 1809 , is shown along with a simplified pattern of veins 1802 / 1814 . As shown, veins are roughly linear structures. Normally, depending on the part of the body the practitioner is attempting vein access, only veins that are oriented in a single direction are typically used to administer medicine or draw blood. For example, on the arm, the veins that run along the long axis of the arm are typically used. Therefore scanning that favors vein detection along that axis is desirable.
[0236] A series of scan lines are shown 1806 , 1810 and 1813 . Each scan line occurs sequentially in time with 1806 first, 1810 second and 1813 last. This technique relies on the fact that once a vein's position is found on a scan line, an assumption can be made where the vein is likely to be on a subsequent scan line. The vein signal can be expected to occur within a small distance to the right or left of the position seen on the previous scan line. Therefore the system can apply a windowing technique wherein vein signals that occur outside the window are given a lower priority or are ignored completely
[0237] Referring to FIG. 15 , a signal diagram to show the windowing approach is provided. 1804 , 1808 , and 1812 are the reflection signals from scan lines 1806 , 1810 and 1813 respectively. In this drawing, a high signal represents greater absorption of the laser light at that point on the body. 1807 , 1811 and 1813 are the “windows” calculated based on 1804 , 1808 and 1812 respectively. In this drawing, when the window signal is high, detection occurs, when it is low, no detection occurs.
[0238] The signal 1800 is caused by vein 1814 and signal 1801 is caused by vein 1802 . This simplified example is for a system that is designed to only show the single largest vein in the field of view. By using a system capable of keeping track of multiple windows, multiple veins could be tracked. Alternatively, the sense can be inverted and the vein within the window could be ignored.
[0239] Vein 1802 is selected as the vein of interest by some criteria, set in the system or by the user, such as size of vein or the central location of the vein in the field of view. Based on the vein's position as detected by the pulse 1801 on the reflection signal 1804 , a window signal 1807 is created that ignores vein reflections that occur outside of the detection window 1805 on the next scan line 1810 / 1808 . Referring to signal 1808 , vein 1814 is ignored since it falls outside the window and vein 1802 is detected since it falls within the window. However, since the vein is traveling at an angle with relation to the scan pattern, the vein is now offset within the window. In order to track the vein on subsequent scan lines, the system now re-centers the window 1811 so that when it is applied to the next scan line 1813 / 1812 , the vein falls within the window. This process repeats for the entire field of scanning.
[0240] A user interface can be implemented allowing the user to select a number of veins to detect simultaneously and to switch focus from vein to vein. Also, the user could control the width of the window to optimize the detection of the vein. Additionally, the user can turn this feature on and off so that they can either see all veins or just a specific vein or veins. Since there is inherent directionality to the procedure, the user can rotate the scanner to see only those veins at a particular orientation.
[0000] Diagrammatic Walkthrough
[0000] Walk Through of the Engine
[0241] In FIGS. 17 through 22 , an embodiment of the device is presented. This implementation uses two lasers, one infrared and one red. The lasers are made coaxial through a series of bounce mirrors and are combined by a dielectric mirror. Two moving mirrors are used to move the beam in a raster pattern which then exits the engine and strikes the patient's body. The collection path includes two spatially separated photo diodes. The electronics use an analog, real time approach whereby the detection of a vein causes an immediate reduction in the projected visible light at the point at which the vein is detected. The operator sees this pattern of dark lines directly on top of the position of the veins.
[0242] Referring to FIG. 17 , the scanning engine is shown as an assembly including a detector deck 1004 , an optical deck 1005 and a circuit board 1006 . Both mechanical and electronic parts are mounted on these boards. The engine is oriented so that the laser scanning pattern 1000 projects perpendicular to the boards through an orifice in the detector deck 1004 . The photo detectors 1001 - 1002 are aimed along the same axis so that they have a clear view of the reflected light.
[0243] In FIG. 18 , the visible laser diode 1015 and infrared laser diode 1019 are arranged for best fit within a miniature form factor of the engine and therefore rely on a series of bounce mirrors to realign the beam. Both laser diodes are mounted to holder assemblies 1023 / 1024 and heat sinks 1016 / 1018 . Proper thermal management of the diodes extends their working life and increases the reliability of the engine.
[0244] An optional connector 1017 is mounted to the side of the engine to allow it to be used in an embodiment of the device that allows the scan head to be removed from the portable handheld device and mounted on an alternative base such as a tabletop stand.
[0245] The detector deck 1020 is a printed circuit assembly that holds the photo detectors 1021 / 1022 as well as other electronic components necessary for the operation of the engine. For example, the pre-amplifier circuitry for the photo detectors will typically be mounted in close proximity to the detectors 1021 / 1022 so that noise in the system is minimized.
[0246] The photo detectors 1021 / 1022 are shown with integrated dome-shaped lenses to increase sensitivity in the direction of the reflected laser. Various schemes both with and without lenses can be implemented in engine embodiments. In addition, filters can be placed in front of the photo detectors so that the wavelength of light they respond to can be specified.
[0247] In FIG. 19 a - c which is an illustrative example, several views of the bounce mirror assemblies are shown. Since the intent of the design is to make two or more laser beams coaxial, proper alignment is critical. Shown is one of the exit windows from the laser diode 1038 with the beam 1037 striking the mirror 1040 thereby reflecting the beam into the new desired orientation 1042 . The mirror is held in position by an adjustable holder 1041 .
[0248] The holder assembly 1041 is comprised of a fixed platform 1031 that is fastened to the optical deck in a fixed manner. The mirror 1032 is attached to a wedge 1034 that is angled in the desired manner to reflect the beam in the appropriate direction. The wedge is fixed to a floating deck 1033 which is attached to the fixed platform 1031 through a number of screw 1035 and spring 1036 assemblies. The spring 1036 is placed around the screw 1035 and is compressed by the two platforms 1033 / 1031 so that the springs provide a constant force against the two platforms ensuring that they are held as far apart as the screws will allow. The screws (e.g., 1039 ) pass through an unthreaded hole in the floating deck and into a threaded hold in the fixed platform 1031 . By tightening or loosening the screws, the decks are moved closer or further apart. Through the use of multiple screws, several degrees of freedom of adjustment are obtained, thereby allowing the beam to be properly aligned along the desired path.
[0249] In this design, three of these bounce mirror assemblies are used. This design uses mechanical screws to fine-tune the position of the mirrors and in practice would be locked in place once positioned with an adhesive material such as locktite. High volume configurations of the product could use robotic assembly and the mirrors would be positioned and then welded, epoxied or glued into place eliminating the cost and complexity of the screw/spring assembly.
[0250] Referring to FIG. 20 , the path of the laser beams are shown. Many parts have been removed from the diagram to allow the beam path to be easily seen. The laser diode 1080 emits a beam 1081 which strikes the angled mirror and is reflected along path 1083 which then strikes the dielectric mirror 1084 . The mirror's characteristics are selected so that this beam passes through mirror 1084 and exits along path 1085 .
[0251] The second laser 1088 emits its beam along path 1089 which then is reflected off of mirror 1090 along path 1091 . The beam 1091 strikes the dielectric mirror 1084 which as been coated to reflect the wavelength of light emitted by laser 1088 . Therefore, the beam is reflected along path 1085 . At this point the two lasers are now coaxial. The beams 1085 are reflected off of mirror 1086 and are reflected along path 1087 so that it strikes the moving mirror that is part of assembly 1087 . This fast-moving mirror is oriented to provide the x-axis scanning. The light is reflected onto the mirror in assembly 1092 which is a slower moving mirror that provides the scanning in the y-axis. In this diagram, the resulting scanned beam pattern exits out towards the back of the drawing.
[0252] In FIG. 21 , which is an alternative view of the previous drawing, the scanned laser beam exit pattern 1095 is seen more clearly.
[0253] In FIG. 22 , additional novel features of the design are seen. The laser diode mounting bracket 1152 , is a split ring design. The screws 159 pass through unthreaded holes in the bracket 1152 and into threaded holes on the optical deck 1160 . By tightening the screw on the split side of the bracket 1152 , the laser diode assembly 1158 is compressed and held in place. This allows the position of the diode to be locked in both an in/out orientation and in rotation. Locking the rotation position is critical in designs that use the laser's polarization rather than wavelength for beam alignment.
[0254] The engine uses extensions 1153 , 1155 , 1157 on the circuit board to provide mounting features so that the entire engine assembly can be firmly mounted into a housing. The extensions could also have been on the detector deck or optical deck or on one or more of the mechanical components of the engine. Holes such as 1154 are provided so that either a screw or a boss can be used to align and hold the engine in the housing. The extensions can be held in place with screws or by captivating them in a feature of the housing. The extensions can be made in a range of shapes so that they do not interfere with features in the housing. For example, the notch 1156 is designed so as not to interfere with a boss in the housing.
[0255] In the current design, the high speed mirror 1111 is implemented with a Texas Instruments TALP3400 and the low speed mirror 1111 is implemented with a Texas Instruments TALP4500. The red laser diode 1111 is a Sanyo DL-LS1148 and the infrared laser diode is a Sanyo GH0781JA2C. The laser lens 1111 is a Thorlabs, Inc. 350150-B and the photo diodes 1111 / 1111 are Hamamatsu S6968-01.
[0256] Referring to FIG. 23 , one embodiment of a portable handheld vein scanner based on the engine described previously described. It will be appreciated that this device is just one example of the design of the present invention and that the shape and features can be altered to fit the end user's needs while still employing the teachings of the present invention. This embodiment is typically a two piece design with a detachable head 1605 connected through a friction fit; a snap on mechanism or other suitable means to a handle 1606 . The buttons 1610 , which are on both sides of the handle, are designed so that when they are pressed, latches that hold the scan head and the handle together are released and the user can separate the two pieces. Screw holes 1600 on both sides of the handle are provided along with matching internal bosses in the scan head allow the handle and head to be permanently attached should the deploying organization wish to prevent the separation of the parts.
[0257] The handle is composed of a top housing 1608 and a bottom housing 1609 that are snapped and screwed together to form a single unit. The battery door cover 1607 completes the handle package. This door cover 1607 is designed to be removed by the user with the latch 1607 . There is also provision for a screw hole in the battery door and a matching hole in the inner housing should the deploying organization wish to prevent the end user from accessing the battery.
[0258] In the top portion of the handle, two LED openings are provided 1603 , 1604 . These are illuminated by LEDs on a board inside the handle and provide important status information to the user. The openings at 1603 and 1604 can be filled with a light pipe or pipes to bring the light up to the top surface and can be covered either with a molded light pipe or with a label that fits into the opening at 1612 . An inset area is provided at 1602 that allows for a label to be positioned providing a company logo, a product model identifier or other user viewable indicia. Since the top and bottom are separable, it may be desirable to repeat identical or other labeling information on the handle part as well. Additional labels can be placed on the inside of the battery door, battery compartment or on or near the scanner opening on the other side of the scan head 1605 .
[0259] As seen in the engine design discussions, thermal management of the laser is critical to minimizing power consumption and life of the laser. Therefore, openings 1601 are provided on both sides of the scan head to allow convection cooling of the scan engine. In certain embodiments, it might be desirable to have a fully sealed unit. In this case, the openings will be eliminated and other techniques well know in the art will be used to cool the lasers. For example, the heat sinks on the engine can be continued on the outside of the housing.
[0260] Views of the handle 1620 separated from the head 1621 are shown in FIG. 24 . 1630 / 1631 are the matching screw holes for the optional screws 1600 . These holes are designed to engage the threads on the screws. The holes 1627 / 1628 line up with these holes and do not engage the threads, but are designed so that the screw heads apply pressure against the head and handle thereby keeping them connected.
[0261] Further screw holes are seen at 1634 , 1633 , 1632 that hold the top and bottom plastic pieces of the scan head together. Internal mating bosses are provided in the lower half of the scan head housing.
[0262] Mating latches 1626 / 1625 and holes 1623 / 1624 hold the scan head and handle together. The latches 1625 / 1626 are internally sprung so that when the buttons 1610 in FIG. 23 are not pressed, they captivate the outside edge of the slots 1623 / 1624 . When the buttons 1610 are pressed, they no longer engage the slots 1623 / 1624 .
[0263] Two mating electrical connectors 1635 and 1622 are provided so that the battery, switch and other electronics in the handle 1620 connect to the electronics in the head 1621 . A shoulder 1637 and a matching inset 1636 are provided to ensure proper alignment of the connectors as the head and handle are separated and re-connected.
[0264] In FIG. 25 , the head and handle are shown attached. A trigger that allows the user to control the operation of the scanner is shown at 1655 and 1662 (See FIG. 26 ). This trigger is molded as part of lower housing 1653 and internally comes in to contact with an electrical switch. The hinged part of the lower housing that forms the trigger 1655 is designed so that it has an appropriate level of force so that the user doesn't accidentally trigger the unit but doesn't have to press to hard either. The mating electrical switch is selected so that the user gets positive tactile feedback of the switch closure.
[0265] The lenses for the photo detectors are shown at 1650 . They are aligned in the same plane as the emitted laser path 1651 so that they can pick up the reflected light from the target area. In FIG. 26 , the photo detectors 1660 / 1663 are shown arranged around the laser exit window 1661 .
[0266] FIG. 27 a is shown with the lower housing of both the handle and the head removed FIG. 27 b showing the position of the scan engine 1670 , the paired electrical connectors 1674 and the electrical switch 1671 that were described earlier. A PCB 1676 is show holding the switch, the LEDs and the connectors 1674 previously described. A second PCB that mates to the battery connectors is at 1673 .
[0267] The battery door spring mechanism is shown at 1675 . The loop in the mechanism provides force in the forward direction (towards the head) thereby engaging the latch. A second view of the door and the latch mechanism is shown in drawing 27 b with the tongue 1697 that engages the handle top housing 1698 and the clip on the latch 1700 that engages the handle top housing at the other end of the battery door.
[0268] One of several screw bosses 1695 is used to connect the top and bottom halves of the housings. Furthermore, an alignment standoff is shown at 1699 .
[0269] Referring to FIG. 28 , which shows the cavity/rear housings of both the head 1685 and handle 1686 , several additional details are revealed. Bosses 1691 and 1687 provide mounting for the mounting tabs on the scan engine described earlier. These can be secured with screws or can be captivated between the two halves of the housing. An alternative design could captivate the engine in shock absorbing materials to increase the ruggedness of the device.
[0270] Further detail of the spring latch mechanism described earlier can be seen at 1688 and the contact point/stud for the electrical switch from the trigger is shown at 1690 .
[0271] Ribbing that performs the multiple function of strengthening the housing and locating the battery is shown at 1689 and 1692 .
[0272] Referring to FIG. 29 , a block diagram of the invention is presented. The electronics system 1747 can be based on discrete electronic components or can have one or more microprocessors and memories 1748 . In this embodiment, a small processor with on chip memory is dedicated to housekeeping functions including laser calibration, proximity sensing, and other system control and setup functions. Additional processing and memory components can be added to perform higher level functions like image-based vein detection.
[0273] In this embodiment, a raster pattern is implemented. A mirror drive subsystem 1738 / 1733 is controlled 1738 / 1735 by the electronics to drive the X mirror 1740 at a higher speed than the Y mirror 1734 to create the raster pattern. The electronics will control mirror on and off, and the mirror will report back when it begins its scan. The mirror drive systems 1739 / 1733 provides the drive waveform to the mirrors 1740 / 1734 that cause them to oscillate at the proper speed and in synchrony. This consists of sine wave to the mirrors. The drive circuitry also contains detection circuitry that uses a feedback path 1737 / 1736 from the mirrors to detect that the mirrors are in motion. In this manner, if a mirror has failed to move, the engine can shut down the lasers to ensure user safety.
[0274] The lasers are also controlled by the main electronics 1747 through a set of drive circuits 1746 / 1742 . These circuits provide the ability to set the intensity of the lasers 1744 / 1741 from off through maximum intensity. In this embodiment, the lasers contain internal mirrors for calibration and which are read back from the lasers 1745 / 1743 and through the drive circuits 1748 / 1750 into the main electronics. The reverse path is used to control the drivers and lasers.
[0275] In this embodiment, a proximity sensor 1725 to detect that there is a surface within working range. The main electronics reads 1729 the sensor to ensure that the lasers are not turned on if there is an object either too close or no object within proximity of the front face of the scanner.
[0276] The photo detection subsystem consists of a pair of photo diodes 1727 and an amplifier 1726 that is fed through 1730 the main electronics for vein detection. A control for setting gain is provided through 1730 .
[0277] Since this is a portable device, power is provided from a battery 1731 , which provides 1752 power to a control circuit 1732 which provides voltage regulation and delivers 1751 the appropriate voltages to the electronics
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The present invention is a Miniature Vein Enhancer that includes a Miniature Projection Head. The Miniature Projection Head may be operated in one of three modes, AFM, DBM, and RTM. The Miniature Projection Head of the present invention projects an image of the veins of a patient, which aids the practitioner in pinpointing a vein for an intravenous drip, blood test, and the like. The Miniature projection head may have a cavity for a power source or it may have a power source located in a body portion of the Miniature Vein Enhancer. The Miniature Vein Enhancer may be attached to one of several improved needle protectors, or the Miniature Vein Enhancer may be attached to a body similar to a flashlight for hand held use. The Miniature Vein Enhancer of the present invention may also be attached to a magnifying glass, a flat panel display, and the like.
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CROSS REFERENCE
This application is related to provisional patent application 60/334,449 filed on Nov. 29, 2001 entitled Cards and is hereby incorporated by reference.
SUMMARY OF THE INVENTION
The present invention relates to educational and entertaining playing cards. The cards may be used alone or in combination with other hardware game accessories, such as board games, or software game accessories, such as compact discs and the Internet. Unlike other popular and heavily traded playing cards (e.g. Pokemon) which have limited social and educational value, an educational element has been added to the cards of the present invention without destroying the fun associated with the collecting, trading, and playing of the cards. Educational facts and information about a variety of topics are located on the playing cards, which may be used to play various games.
Two different types of game cards are contemplated by the present invention: (1) standard cards and (2) fact cards. The present invention, however, is in no way limited to only these two types of game cards.
BRIEF DESCRIPTION OF THE DRAWINGS
These and other features, aspects, and advantages oft he present invention will become better understood with regard to the following description, appended claims, and accompanying drawings where:
FIGS. 1–4 illustrate a first embodiment having standard cards;
FIG. 5 illustrates a second embodiment having fact cards;
FIG. 6 illustrates a special decoder;
FIG. 7 illustrates following an arrow through maze; and
FIG. 8 illustrates a board game embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to educational and entertainment uses of playing cards. There are several embodiments for the instant invention including: standard cards; fact cards; computer games; a board; and trading cards.
(1) Standard Cards (see FIGS. 1–4 )
As with any ordinary deck of cards, in a preferred embodiment at least fifty-two standard cards are provided. The fifty-two standard cards may be divided equally into four categories and numbered “1” to “13” within each category. The four categories may be analogous to the four suits in a standard deck of cards (Hearts, Clubs, Spades, and Diamonds) and the 1–13 designation on the cards may be analogous to the 2–10, Jack, Queen, King, and Ace designation on the cards of a standard deck. However, those skilled in the art will recognize that the deck may contain more or fewer than fifty-two cards and that such cards need not necessarily be divided either equally or into four categories and may be numbered or otherwise labeled or marked differently than heretofore described.
Each standard card within a category may contain pictures, descriptions, and other interesting factual information about that category. It is preferable but not required that all of the categories of the standard cards be related so that the cards have a common theme. For example, each of the four categories could be a different food group (e.g. Breads and Grains, Dairy, Fruit and Vegetables, Meats and Proteins) and each card within each category could highlight a different food within that food group. Alternatively, each of the four categories could be a different continent (e.g. Africa, Australia, Asia and Europe) and each card within each category could highlight a different city within that continent. Those skilled in the art will recognize that the themes for the various card categories can be drawn from a myriad of subjects, including, but not limited to, Astronomy, Biology, Physiology, Languages, Types of Wine, Sports, Modes or Transportation, Materials, Colors, Cars, Zoology, etc. For purposes of discussion and illustration, the categories of the cards of a preferred embodiment of the present invention are different animal habitats (e.g., Mountains, Desert, Rain Forest, and Plains) and each card within each category contains pictures, descriptions, and other interesting factual information about a different animal living within that habitat (e.g., in FIG. 1 a Bald Eagle 100 , in FIG. 3 a Desert Finch 200 , in FIG. 3 a Parrot 300 , and in FIG. 4 a Roadrunner 400 , respectively). In a further embodiment, the content and numbering of the cards may be designed in a manner that the cards that are numbered the same (e.g. the number “ 10 ” cards as shown in FIGS. 1 , 2 and 4 as 102 , 202 and 402 respectively) have related subject matter across all categories (e.g. all the number 10 cards could be types of snakes).
In addition to the fifty-two numbered standard cards, additional standard cards containing information about different animals within one of the four habitats or, alternatively, introducing new habitats (e.g. Ocean, Polar, Tundra, etc.) and highlighting animals living within those new habitats, may be provided. These additional standard cards typically should not be numbered so that the user may readily identify the standard cards (i.e., the numbered ones) to be used in connection with standard deck card games. Again, however, these additional cards (if present) may contain different information than described above and may indeed be numbered if appropriate or desired.
(2) Fact Cards (see FIG. 5 )
In addition to the standard cards, fact cards containing interesting trivia information or questions may be provided as a supplementary education tool. It is preferable, but not required, that the trivia information 502 relate to the subject matter of the standard cards (i.e., in this example, the trivia questions relate to animals within the different Habitats) so that the cards have a common theme as shown in FIG. 5 500 . To enhance the appeal of answering the trivia questions, the answers on the fact cards are preferably, but do not have to be, hidden or disguised in a manner that requires deciphering or decoding. Masking of the answer may be done in numerous ways. For example, the correct answer may be a three-dimensional (“3-D”) image on the card and therefore require the user to don 3-D glasses to identify the correct answer. Alternatively, the answer could be hidden under a surface coating that must be “scratched off” (like a lottery ticket). Or, alternatively, a special decoder 600 (see FIG. 6 ) may be used to identify the correct answer to the question by positioning the fact card 602 on the decoder and following the arrow 702 through the maze (see FIG. 7 ). In this example, the first letter encountered along the maze is the correct answer. Any means for hiding and deciphering the correct answer may be provided, however, and the present invention is in no way limited to these few examples.
The cards of the present invention have a variety of applications, including, but not limited to, the following:
A. Card Games
Because of the similarities between a standard deck of cards and the fifty-two numbered standard cards, virtually any card game one can play with an ordinary deck of cards can be played with the numbered standard cards. In addition to standard card games, the users are encouraged to develop alternative games:
(1) Wildlife Survival (for 2 players)
Object: To be the first player to win all cards from their opponent.
Dealer: Dealer shuffles the cards and deals out 26 cards to each player, one at a time, face down. Do NOT look at your cards. Put them in a face down stack in front of you.
Play: Each player turns over the top card and puts it beside their stack, face up, so that their opponent can see it. One of three situations will occur:
If the two exposed cards are DIFFERENT ANIMALS from DIFFERENT HABITATS, then the player with the higher numbered card wins the “Battle” and collects his opponent's card.
If the two exposed cards are animals from the SAME HABITAT, then the winner of the “Battle” is determined by the FOOD, SHELTER, PREDATOR, and WEATHER emblems on the cards. Although not present on the embodiments shown in FIGS. 1–4 , a FOOD, SHELTER, PREDATOR, or WEATHER emblem is preferably located on each card. The hierarchy of the emblems is as follows:
FOOD beats SHELTER and WEATHER SHELTER beats PREDATOR and WEATHER PREDATOR beats FOOD WEATHER beats PREDATOR
If the emblems are the same, then the higher numbered card wins.
If the two exposed cards are the SAME TYPE OF ANIMAL (e.g. Birds) from DIFFERENT HABITATS, then the winner is determined by the FOOD, SHELTER, PREDATOR, and WEATHER emblems at the bottom of each card.
Battle continues until a player wins all the cards from his opponent.
(2) Animal Noises (for 2 or more players)
Object: To win all the cards.
Set up: All players decide what animal they want to be. Make that animal's noise—meow, squeak, and quack, whatever. Each player should choose a different animal. Make sure the other players know what animal they're supposed to be. And remember what animals they are too—you'll need to know. Everyone picks a card from the deck—whoever has the highest card deals.
Dealer: Shuffle the cards. Deal them all out one at a time and face down. It doesn't matter if some people have more cards than others.
All Players: Do NOT look at your cards. Put them in a face down stack in front of you.
Player on dealer's left goes first. Turn over the top card and put it beside your stack, face up, so everyone can see it. Everyone takes a turn with play going around to the left. Each player turns up a card. Keep an eye out for the moment when someone else turns up a card that matches—by number or type of animal—your face up card. You may have a few turns before this happens. As soon as you spot the match, make the other player's animal noise three times in a row. Then take the other player's face up pile and add it to your own face down stack.
If both players spot the match at the same time, the first one to finish making the noises gets the pile.
If you make the wrong noise, you have to give your face up pile to the player with the matching card.
If you run out of cards in your face down stack, just turn over your face up stack and keep going.
The game ends when one person has won all the cards. Winner gathers up the cards and deals next round.
(3) My Kingdom Rules (for 4 to 6 players)
Object: To be the first player to collect seven cards of the same suit (i.e. Habitat)
Set Up: All players pick a card from the deck. Whoever has the highest card deals.
Start: Dealer shuffles the cards and deals out seven cards to each player, one at a time, face down. Put the rest of the deck to one side—you won't be using it again for this game.
All players pick up their cards. Arrange them into Habitats (i.e. suits) so that you can easily see what you have most of. Decide what Habitat to collect. But, be prepared to change your mind during the game. Choose a card that you don't want. Put that card face down in front of you.
Play: All players slide the card you don't want to your left hand neighbor. Pick up the card your right hand neighbor slides to you. Keep on passing and picking up cards, trying to get a hand of cards all of the same Habitat. The first person to have seven cards of the same Habitat shouts “My Kingdom Rules!” and is the winner.
B. Computer Games (CD ROM, Internet, etc)
The cards may also be used with games available on a CD ROM or Internet website specifically designed to be “interactive” with the cards. The game cards may contain special passwords that are encrypted as pictographs (i.e. a picture that denotes a word or phrase), as shown in FIGS. 1–4 . The pictographs may, but do not have to be, hidden within the card so that the user first must locate the pictograph before it may be deciphered. The pictographs may act as passwords to permit access by the user to different games and different levels of the games available for play. For example, to move to the next level within a game, the computer may prompt the user to enter the password from the Parrot card (i.e. “sunflower”). If the user does not have the Parrot card, he must obtain it before progressing in this particular game. Therefore, without the correct cards and passwords access to the games is limited. This helps ensure that the users will desire to collect all of the cards to enable access to all games and levels therein. Alternatively, users will seek the cards and corresponding passwords from their peers, thereby, stimulating greater appeal and interest in the game. To add further challenge to the use of passwords for game play, the pictographs may be color coded such that the user may be required to combine, for example, only the “blue” pictographs to form a word or phrase permitting special access to the game. Those skilled in the art will recognize that the pictographs may represent simple or complex words or phrases and can be designed to be age appropriate for any targeted user base.
An example of a computer game that is interactive with the cards involves the user maneuvering through different animal habitats in order to give the user a sense of what it is like to explore nature. Aboard the BIOmobile the user travels to the Mountains, Savannah, Rain Forest, Desert, Ocean, Arctic, and Australian Outback where special Habitat Hosts, such as Peter the Parrot (Rain Forest) and Steve the Salamander (Desert), act as the users' guide. Using a map and compass, the users explore each habitat and learn about how animals feed, move, grow, and use their senses to remain alive. Armed with clues, users must locate certain animals and, with each successful find, earn the needed food and water for their guide. Each habitat may be filled with a plethora of trails containing fun arcade-style games and academic challenges. Secret passwords, available only from the game cards, control access to various levels of the game. New trails become “activated” or accessible after a predetermined level of completion within each habitat or as certain passwords are obtained. As levels are completed, the user may earn stickers, certificates and special photo shoot opportunities with their favorite animals (all available for downloading and printing). To assist in the educational aspect of this game, the program may have a searchable database of animals and facts and multiple hyperlinks. This database may also contain brief photos, sounds and video. Connection to animal-related websites on the world wide web (including links to live CAM shots at various national zoos) provides for an additional learning resource.
The method and system described in these computer applications herein can be embodied in the form of computer-implemented processes and apparatuses for practicing those processes. The present method and system can also be embodied in the form of computer program code containing instructions, embodied in tangible media, such as floppy diskettes, CD-ROMs, hard drives, or any other computer-readable storage medium, wherein, when the computer program code loaded into and executed by a computer, the computer becomes an apparatus for practicing the method and system. The present method and system can also be embodied in the form of computer program code, for example, whether stored in a storage medium, loaded into and/or executed by a computer, or transmitted over some transmission medium, such as over electrical wiring or cabling, through fiber optics, or via electromagnetic radiation, wherein, when the computer program code is loaded into and executed by a computer, the computer becomes an apparatus for practicing the method and system. When the implementation is on a general-purpose microprocessor, the computer program code segments configure the microprocessor to create specific logic circuits.
The apparatus and method of implementation of card games with a computer may be accomplished using an article of manufacture, computer program product program or program storage device having a computer usable medium having computer readable program code embodied therein for playing a card game. The computer readable program code in the article of manufacture includes a computer readable program code means for interactive card playing. The article of manufacture may additionally include computer readable program code receiving cpded passwords. The article of manufacture may be a complete program within a computer usable medium having computer readable program code means embodied therein for playing a card game. The computer readable program code in the article of manufacture includes computer readable program code for for interactively playing a card game and accepting and responding to encrypted passwords.
C. Board Game (see FIG. 8 )
The cards may also be used in combination with any number of board games 800 , an example of which follows:
Object of Game: To Rule the Kingdom by mastering all Four (4) animals in any one Habitat (e.g., Plains, Rain Forest, Mountains, Desert, Arctic, and Antarctic).
Rules:
1. Select game piece (6 colored animal pieces to choose from) and corresponding colored markers that uniquely identify each player. Place game piece at Lodge 802 (located on board).
2. Shuffle the cards and place on designated place on the board 804 .
3. Each player turns over a card. Highest goes first.
4. Using the deck of cards, a player must get an EVEN numbered card to Exit the Lodge and Enter a Habitat. Enter any Habitat at the area marked SHELTER 806 .
5. Players take turns drawing a card (clockwise order). Move the game piece the number of spaces indicated by the number on the card.
6. Follow written instructions on board.
7. If you land on an animal not already “mastered” by another player (i.e., no colored marker is on the animal), you can attempt to master that animal by “Waging a Battle” against your opponent. (When playing with 3–6 players, wage battles with opponents on your right). If you win the battle, then player places a marker on the space represented by the animal indicating that player is the master of that animal. If you lose the battle, then your turn is over and no marker is placed on the board.
8. If you land on an animal already “mastered” by another player (i.e., a colored marker is on the animal), you must “Wage a Battle” against the opponent who currently is the master of that animal. If you win the battle, then player is allowed to go free on his next turn with no consequences. If you lose the battle, then you must remove one of your markers from the board. If you do not have any markers, then you must return to the Lodge.
Winning: The winner is the first player to master all the animals in any one HABITAT.
To Wage a Battle: Each player in the battle selects a card from the card deck and turns it face up on the board. One of three situations will occur:
A. If the two exposed cards are DIFFERENT ANIMALS from DIFFERENT HABITATS, then the player with the higher numbered card wins the “Battle”.
B. If the two exposed cards are animals from the SAME HABITAT, then the winner of the “Battle” is determined by the FOOD, SHELTER, PREDATOR, and WEATHER emblems at the bottom of each card. Note:
FOOD beats SHELTER and WEATHER SHELTER beats PREDATOR and WEATHER PREDATOR beats FOOD WEATHER beats PREDATOR
If the emblems are the same, then the higher numbered card wins.
C. If the two exposed cards are the SAME TYPE OF ANIMAL (e.g. Birds) from DIFFERENT HABITATS, then the winner is determined by the FOOD, SHELTER, PREDATOR, and WEATHER emblems at the bottom of each card.
Board Terminology
Return to Lodge—means return game piece to Lodge. As before, player must draw an even numbered card to exit Lodge and return to HABITATS.
Roll Again—take another turn.
Lose Turn—forfeit your next turn.
Open Challenge—Wage a Battle against any other player of your choosing. Loser of the battle must remove one of their markers from the board. The player landing on the OPEN CHALLENGE space can choose not to challenge another player.
Return to Rainforest, Mountains, Desert—means move your game piece to the SHELTER space of that HABITAT
D. Trading
In addition to the cards' use in conjunction with various games (card games, computer games, board games, etc.) and overall educational appeal, the cards may also be traded. To further enhance the collectability and tradability of the cards, additional features, such as 3-D imaging, holographic imaging, scratch and sniff patches may be added to the cards.
The foregoing is provided for the purpose of illustrating, explaining and describing embodiments of the present invention. Further modifications and adaptations to these embodiments will be apparent to those skilled in the art and may be made without departing from the spirit of the invention or the scope of the following claims.
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The present invention relates to educational and entertaining playing cards. The cards may be used alone or in combination with other hardware game accessories, such as board games, or software game accessories, such as compact discs and the Internet. Unlike other popular and heavily traded playing cards (e.g. Pokemon) which have limited social and educational value, an educational element has been added to the cards of the present invention without destroying the fun associated with the collecting, trading, and playing of the cards. Educational facts and information about a variety of topics are located on the playing cards, which may be used to play various games. Two different types of game cards are contemplated by the present invention: (1) standard cards and (2) fact cards. The present invention, however, is in no way limited to only these two types of game cards.
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CROSS REFERENCES TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part application of application Ser. No. 10/883,406 filed Jun. 30, 2004, which claims priority of U.S. Provisional Application No. 60/484,234 filed Jun. 30, 2003, the entire disclosure of which are hereby incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] Adenoviruses commonly infect the eye, respiratory and gastrointestinal tracts and can infect other organs such as the liver, urinary bladder, pancreas, central nervous system and others. There are over 50 known serotypes of Human Adenoviruses of which at least 24 have been identified as pathogens. Adenovirus has been shown to persist for months after initial infection in particular in immunosuppressed patients.
TABLE 1 Adenoviruses Serotypes and Disease Disease Major Serotypes* Acute febrile pharyngitis 1, 2, 3, 5 , 6, 7 Acute respiratory disease 3, 4, 7 , 14, 21 Acute hemorrhagic cystitis 11, 21 Epidemic keratoconjunctivitis 8, 11, 19, 37 Gastroenteritis 40, 41 Hepatitis 1, 2, 5 Meningoencephalitis 7 , 12, 32 Pertussis-like syndrome 5 Pharyngoconjuctival fever 3, 7 , 14 Pneumonia (children) 1, 2, 3, 7 Pneumonia (adults - military recruits) 4, 7 *Serotypes in bold with underline have been tested and shown to be sensitive to CTC-96
An example of Adenovirus-Related Disease
[0003] Adenoviruses are the most prevalent causes of acute ocular viral disease for which there is no known cure. The actual prevalence and incidence of Epidemic Keratoconjunctivitis (EKC) caused by Adenoviruses in the U.S. and internationally are unknown, because general practitioners and optometrists see most cases and this infection does not have to be reported to any medical authority. EKC is highly contagious and has the tendency to occur in epidemics.
[0004] While EKC is a self-limiting disease that generally resolves within 1-3 weeks the patient may remain highly infectious for 10-14 days or more after symptoms develop (I). Symptoms of EKC include conjunctival redness, swelling or redness of the eyelid, discharge from the eye, sticking together of eyelids, pain or discomfort in the eye, photophobia, or a sensation of a foreign body in the eye. In Severe cases, membranous and pseudomembranous conjunctivitis can be seen in one third of cases, which can lead to conjunctival scarring and symblepharon formation (adherence of the bulbar and palpebral conjunctivas) (2; 3). Both membranes and pseudomembranes can occur in EKC with a distinguishing corneal involvement that ranges from diffuse, fine, superficial keratitis to epithelial defects to subepithelial opacities (2; 3). In 20-50% of cases, corneal opacities can persist for weeks to months to several years (I; 3). This phenomenon can decrease visual acuity significantly and cause glare symptoms (2).
[0005] There is no specific direct antiviral chemotherapy against Adenoviruses at present. Corticosteroids may be used to limit corneal damage but have the side effects referred to above and also of interfere with viral clearance (3; 4).
SUMMARY OF THE INVENTION
[0006] We have discovered an effective method for the treatment for Human Adenoviruses, and, in particular, Adenovirus-derived keratoconjunctivitis for both therapeutic and prophylactic purposes and respiratory disease. The treatment for adenovirus-derived keratoconjunctivitis, whether it be for therapeutic or prophylactic purposes, can be achieved by topical administration. The treatment for respiratory disease may be by injection or by nasal administration, i.e., by spray or nose drops. As used herein, the expression “therapeutic treatment” means treatment for a subject already having the disease. As used herein, the expression “prophylactic treatment” means treatment for a subject who, while not being infected by the virus, is in a situation wherein they are susceptible to or subject to the possibility of acquiring the disease, e.g., in a household where another resident is already infected with the disease. We have also shown in vitro that CTC-96 is effective against types 1, 2, 3, 4, 5, and 7, attesting to the effectiveness of CTC-96 against the adenovirus derived diseases outlined in Table 1. More particularly, we have discovered that in the eye there is a significant reduction in Adenovirus-derived keratoconjunctivitis disease can be achieved by the by the topical administration of an anti-adenovirus therapeutic or prophylactic effective amount of Compound CTC- 96 .
[0007] As used herein, the word “therapeutic” means use of the inventive method to treat a subject who has already been infected with Adenovirus. As used herein, the word “prophylactic” means use of the inventive method to protect or decrease the likelihood of a subject who may be exposed to Adenovirus from being infected with the virus.
Compound CTC-96 has the structure:
wherein R 1 and R 1′ are methyl, R 2 and R 2′ are hydrogen and R 3 and R 3′ are methyl, and X and X′ are each:
and Q′ is Br = .
[0008] CTC-96 may be prepared by the method described in the U.S. Pat. No. 5,756,491, the contents of which are hereby incorporated by reference.
[0009] Generally, this compound is administered topically in the form of an aqueous solution.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 is a graph of Human Adenovirus titers following exposure to CTC-96 prior to cell infection;
[0011] FIG. 2 is a graph of virus tiers after exposure of Human Adenovirus infected cells to CTC-96;
[0012] FIG. 3 is a graph depicting the effect of treatment of Adenovirus Induced Keratoconjunctivitis with CTC-96; and
[0013] FIG. 4 is a graph depicting adenovirus titers after treatment of Adenovirus infected rabbit eyes with CTC-96.
[0014] FIG. 5 is a draft of virus titers versus drug concentration.
[0015] FIG. 6 is a draft of virus titers versus drug concentration.
[0016] FIG. 7 is a draft of virus titers versus drug concentration.
[0017] FIG. 8 is a draft of virus titers versus drug concentration.
[0018] FIG. 9 is a draft of virus titers versus drug concentration.
DETAILED DESCRIPTION OF THE INVENTION
[0019] We have demonstrated, by using Adenovirus type 5, that we can reproduce human Adenovirus Infection in rabbit eyes and have shown both excellent antiviral activity and conjunctivitis therapy using CTC-96 which we believe is unique as there is no effective drug against this virus and its pathology in the eye. In addition, we have shown CTC-96 efficacy against Adenovirus types 1, 2, 3, 4, 5, and 7 in HeLa cells in tissue culture. Since these human viruses cannot be grown in animal models, this provides an excellent indication of the effectiveness of CTC-96 against a broad spectrum of Adenovirus types. To determine CTC-96 efficacy against several types of serotypes of adevirus the following procedure was followed:
[0020] 1. Hela cells were confluent at the time of inoculation.
[0021] 2. Virus dilutions were prepared from the known titers of the stock viruses (4×10 5 pfu/ml; 4×10 4 /0.1 ml) of Ad1 Kmetz, Ad2 Wolf, Ad3 Holyfield, Ad4 Harris, Ad7a Joseph, ATCC. This virus inoculation yielded a virus infection with an m.o.i. (multiplicity of infection) of approximately 1.0.
[0022] 3. 100 □l of each Ad serotype were inoculated onto cultures containing Hela cells.
[0023] 4. During the adsorption period, Doxovir concentrations of 500, 250, 100, 50, 10, and 0 μg/ml were prepared in culture medium according to the dilution protocol.
[0024] 5. Virus was adsorbed at 37° C. in a 5% CO 2 water-vapor atmosphere for 1 hour.
[0025] 6. After adsorption, the virus inocula were removed from all the wells and 2 wells each were overlayed with 1 ml of Doxovir (in tissue culture medium) at concentrations of 500, 250, 100, 50, 10, and 0 μg/ml.
[0026] 7. The plates were incubated at 37° C. in a 5% CO 2 water-vapor atmosphere for 24 hours.
[0027] 8. After 24 hours, the plates were washed.
[0028] 9. Each well was refilled with 1 ml of fresh tissue culture medium without Doxovir.
[0029] 10. The cells were scraped from the wells.
[0030] 11. The media and cells were then frozen at −75° C. pending titrations.
[0031] 12. Titration of duplicate samples were thawed from each Ad serotype, Doxovir concentration and its no drug control.
[0032] 13. Viral titers were determined at each drug concentration.
[0033] CTC-96 has considerable advantages as an anti-viral drug: a) because of its unique mode of action it Is effective against herpes and HIV virus mutants which are resistant to currently used drugs; b) because the drug acts against two different viral targets in herpes virus the development of CTC-96-resistant mutants is deemed to be extremely rare; and c) because CTC-96 has anti-inflammatory properties its use replaces the use of steroids in herpes virus and Adenovirus therapeutics. Steroids modulate the immune response in the areas where they are applied and increase tissue susceptibility to pathogens.
[0000] Efficacy Studies
[0034] Efficacy of CTC-96 against Adenovirus types 1, 2, 3, 4, 5, and 7 in culture
[0035] Anti-adenovirus activity of CTC-96 was evaluated by standard cell culture using HeLa cells, a human cervical carcinoma immortalized cell line (the usual host for laboratory grade adenovirus) and anti-viral plaque-reduction assays. CTC-96 has an inhibitory (prophylactic) effect on growth when virus is exposed to the drug prior to cell infection.
[0036] FIG. 1 shows Adenovirus type 5 titers following direct exposure of the virus to CTC-96 prior to HeLa cell infection.
[0037] The data graphically depicted in FIG. 1 were obtained as follows: varying concentrations of the CTC-96 were mixed with concentrated Human Adenovirus, [Adenovirus type 5 (Ad5)] and incubated at 37° C. for 60 minutes. Aliquots were then diluted 500 fold into growth medium. Hela cells were exposed to 100 μl of the diluted material to initiate infection. These monolayers were incubated for 24 hours at 37% and 5% CO2 and then washed, scraped, sonicated, centrifuged and the supernatant serially diluted. These serial dilutions were plated onto indicator HeLa cell monolayers and adsorbed for 60 min, aspirated and a methycellulose overlay placed over the cells, which were then incubated for 3 days at 37%. Cultures were counterstained with 1% methylene blue, allowed to dry and the plaques counted. Results are expressed as mean±SD (where error bars are not visible they are contained within data point).
[0038] CTC-96 also has a potentially therapeutic effect as can be seen by inhibition of viral growth in Adenovirus infected cells, which are subsequently exposed to the drug. FIG. 2 shows virus titers obtained after exposure of human Adenovirus type 5 (Ad5) infected HeLa cells to CTC-96. These data were obtained as follows: Adenovirus was adsorbed onto HeLa cell monolayers for 60 min at 37%; serial dilutions of CTC-96 were overlaid onto the minelayers. Monolayers were then incubated for 24 hr at 37° C. and 5% CO2. Monolayers were then washed, scraped, sonicated, centrifuged and the supernatant serially diluted. These serial dilutions were plated onto indicator HeLa cell monolayers and adsorbed for 60 min, aspirated and a methylcellulose overlay placed over the cells, which were then incubated for 3 days at 37%. Cultures were counterstained with 1% methylene blue, allowed to dry and the plaques counted. Results am expressed as mean & SD (where error bars are not visible they are contained within data point).
[0039] Clinical results and plaque assay viral titers of three CTC-96 treatment/dosing regimens of rabbit eyes infected with Human adenovirus, Adenovirus type 5 (Ad5), were evaluated. On “Day 1” animals were infected with Human Adenovirus Type 5 by the installation of 10 6 pfu adenovirus according to our protocol of conjunctival and corneal scarification for the induction of Keratoconjunctivitis. Clinical conjunctivitis was observed in all animals by day 8 post-inoculation. Animals were then randomized and the following experimental groups were treated with CTC-96 or placebo in a double blind experiment:
(1) Placebo (diluent alone), 9×/day, for 21 days: (4 rabbits). (2) CTC-96 50 μg/ml, 9×/day, for 21 days: (4 rabbits). (3) CTC-96 50 μg/ml, 6×/day, for 21 days: (4 rabbits). (4) C T W 25 μg/ml, 6×/day, for 21 bays: (4 rabbits).
[0044] Clinical disease progression and resolution were evaluated by slit lamp microscopy on days 1, 3, 7, 10, 13, 18, 21, 24, 28 and 31 after initial drug dosing. The intensity of the keratitis was quantified using a clinical grading system (5).
[0045] Application of 25 μg/ml and 50 μg/ml prevented progression of disease severity. Application of 50 μg/ml 6 or 9 times a day for 21 days resulted in complete resolution of clinical disease by day 21 while placebo treated animals continued to show symptoms for another 10 days.
[0046] The results are depicted in FIG. 3 which shows CTC-96 treatment of Adenovirus induced keratoconjunctivitis. The data In FIG. 3 were obtained as follows: rabbits were infected with Human Adenovirus Type 5 by the installation 10 6 pfu adenovirus according to our protocol of conjunctival and corneal scarification for the production of Keratoconjunctivitis. On day 8 post-inoculation treatment with eye drops containing CTC-96 or placebo was initiated. Animals were examined for stromal keratitis and scored by the corneal disease scale of Wander et al. (5). The following are the Criteria For Determination Of Conjunctival Disease:
Area of Conjunctival Disease Conjunctival Severity 0 Normal cornea. 0 Normal conjunctiva. +1 ≦25% involved. +1 Mild conjunctival injection. +2 >25%, ≦50% involved. +2 Moderate conjunctival injection/ chemosis. +3 >50%, ≦75% involved. +3 Severe conjunctival injection/ chemosis. +4 >75%, ≦100% involved. +4 Pseudomembrane present.
[0047] The efficacy of CTC-96 treatment of rabbit eyes infected with Human adenovirus, Adenovirus type 5 (Ad5), was also evaluated by adenovirus recovery from tear film cultures adsorbed onto confluent HeLa cell monolayers. Application of 50 μg/ml 6 or 9 times a day resulted in a rapid fall in viral presence in the eye with no detectable virus by day 13 while placebo treated eyes continued to show detectable virus until day 24. FIG. 4 shows adenovirus titers after treatment of rabbit eyes with CTC-96 or placebo. These data were obtained by the following procedure: rabbits were infected with Human Adenovirus Type 5 by the installation 10 6 pfu adenovirus according to our protocol of conjunctival and corneal scarification for the production of Keratoconjunctivitis. On day 8 post-inoculation treatment with eye drops containing CTC-96 or placebo was initiated. Adenovirus recovery from tear film was evaluated by plaque assay on confluent HeLa cell monolayers. Data are presented as Average±SD.
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A method for the therapeutic and prophylactic treatment of adeviruses, More specifically, a method for the therapeutic treatment of adenovirus in a subject by topically administering an antiviral effective amount of CTC-96 to the subject. In addition, a method for the prophylactic treatment against an adenovirus infection in a subject by topically administering a prophylactically anti-adenovirus effective amount of CTC-96 to the subject to minimize the likelihood of the subject veing infected by the adenovirus.
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BACKGROUND OF THE INVENTION
The subject matter of the present invention relates to a novel non-polluting roadway, highway and walkway chemical deicer featuring the discovery of a means to produce coarse particles of the chemical, which are necessary to an economical ice-melting mechanism. At the same time these particles are relatively non-friable and possess unusual crush strength, attributes which are mandatory for an industrial chemical which is to be stored, handled, shipped, and dispensed on a large scale. Hitherto this non-polluting chemical, calcium acetate, was only available as a fine, dusty powder, a form in which it is totally unacceptable as a chemical deicer.
The production of a coarse, hard particle of calcium acetate was found to be far from straightforward. Repeated attempts were unsuccessful in the beginning, until it was learned that such factors as water content, magnesium ion content, and drying conditions were highly critical for the wet-particle precursors to the final product.
DESCRIPTION OF THE PRIOR ART
Since the early 1940's the use of chemical deicers for roads, highways and walkways has expanded dramatically in the United States. It has been responsible for improving driving conditions for motorists to the extent that a significant reduction in wintertime accidents has occurred. This has not only reduced human tragedy, medical costs, and insurance costs, but also reduced production lost-time due to accidents on the road, disability and death due to highway accidents, and tardiness in arriving at the work place due to highway ice-related delays.
The chemical deicer industry is large by any national standard. Salt, or sodium chloride, is the most widely used surface deicer in the United States today, the estimated usage rate being 12 million tons per year. Calcium chloride is the second most widely used deicer, and is used at only 1 to 2% the rate of salt. Its tonnage is nonetheless substantial, and as a polluter of the environment it is even more undesirable than salt. Various other chemicals are used in deicing at relatively insignificant tonnages. None of these are as intrinsically effective as salt or calcium chloride, nor are they as cost-effective. They are also all more or less environmentally unacceptable depending upon which property is highlighted, viz., metal corrosion, contamination of groundwaters, etc.
According to widely publicized reports by the U.S. Environmental Protection Agency (EPA) the environmental cost to society associated with the use of salt deicer is about 14 fold the cost of the chemical and its disbursement. Untold damage caused by the chloride component of salt includes metallic corrosion of bridge structures and roadway vehicles. The sodium component of salt has been found to increase the sodium level of groundwaters to dangerous levels in many instances. Salt is detrimental to the structure of soil, with consequent accelerated wind and rain erosion. Hence there is great incentive in the national interest to discover a relatively economical non-polluting alternative to salt.
Calcium acetate, and calcium acetate containing a certain amount of magnesium ion represent an economically viable alternative to salt in view of the EPA findings. While the basic concept of using calcium acetate as a deicer is in the public domain and is therefore unpatentable in the United States, there are several related products and processes which have sprung from that basic concept, and these are the subjects of my several co-pending U.S. patent applications.
Whereas the use of calcium acetate as a deicer has been much discussed, apparently no one has recognized that the material in its well-known form of dusty, finely divided powder is totally unacceptable for the melting of ice on roadway and walkway surfaces. Furthermore, the chemical in its familiar form is not adaptable to existing storage, handling and spreading hardware and practices. If the material is to be acceptable it would have to be transformed by physical, physicochemical, or chemical modification into a hard, coarse, non-friable particle. This had not been done, let alone attempted.
It should be clearly understood that it is the ice-melting mechanism itself which is the major concern here, and not the physical form of the chemical as that relates to storage and handling. It is conceivable that new storage and handling methods would be developed to accommodate the new chemical, although that prospect is remote. To reiterate, a fine powder is unacceptable whereas a coarse, dense particle is required. And such a coarse particle would have to be relatively non-friable so that it did not degrade to any significant degree to a powder during handling and dispensing. It ought to have sufficient crush strength as well, to withstand the pressure within a storage container such as a silo.
The ice-melting mechanism is the key to the necessity for a chemical in a definite physical form, and is central to understanding the discovery which is the subject of my present invention. As in most industrial practices, it is ultimately a matter of economics. In simple terms the dispensing of a fine powder deicer represents a waste of chemical. To express it another way, a given chemical in powder form would require much higher doses to effectively remove ice than would the same material in coarse form. By "coarse" here is meant something averaging pea-size, a granulation familiar to anyone who has seen crushed rocksalt deicer.
A coarse deicer particle "bores a hole" through the ice layer due to its concentration at a single point. Ideally, it bores its way to the roadway or walkway surface. The deicer in solution form, or "brine" as it is called in the trade, then spreads into the pavement-ice interface. Thus the interface is weakened, and the ice layer is undercut, so to speak. This results in fracture of the ice layer under the impact of roadway vehicles. The fractured ice soon gives way to clear pavement with continued traffic. Additionally, the effects of deicer enable snow removal equipment to subsequently remove these ice layers with much greater ease. The equipment fractures the ice layers and then pushes them aside, a process obviously facilitated by a weakened ice-pavement interface.
In other words, a general lowering of the melting point of ice everywhere at the ice-air interface is not only unnecessary, but is wasteful of chemical. The actual melting of entire ice masses on roadway or walkway surfaces, it is seen, is not necessary to the ultimate coal of improved vehicle or foot traction. To melt all of the ice would require mammoth amounts of chemical, perhaps as much as ten times the normally applied dosages. This means not only the obvious increase in chemical costs and dispensing round-trips, but also a contamination of the environment approaching emergency status.
A deicer in fine powder form, it is now clear, would penetrate only a limited depth of the ice layer where its melting action would be virtually halted. Its near-neighbor particles would function in the same manner. The result would be a general melting at the original ice-air interface and at some limited depth below it, with no penetration to the pavement-ice interface. In order to accomplish the latter, a massive dose of powder would be required.
Salt easily meets a coarse particle requirement. It is dry-mined, crushed to size, and is shipped either in bulk or in bags to its destination. It is dispensed from mechanical devices known as spreaders directly to road surfaces and areas such as parking lots. Small quantities are hand-broadcast.
Calcium chloride is always in aqueous solution form, deriving mainly from Solvay soda ash operations or from magnesium production. It must be dried to a solid hydrate form or to a relatively anhydrous form in order to function as a deicer. Two types are used today, one a flake made in a flaking/drying operation, and the other is a spherical pellet. The advertising and promotional literature in each case touts the advantageous physical form as concerns deicing effectiveness.
Incidentally, impure calcium chloride liquor has been used on rare occasions to treat roadways in winter. This use is limited to areas close to brine producing plants and is not generally considered as an economical operation.
As for the intrinsic merits of calcium acetate as a deicer, these have been covered in several of my co-pending U.S. patent applications. The present invention focuses upon the physical form of the agent, and the means to attain it. From the foregoing it should be appreciated that the physical form of deicer is of major importance to its overall economical use.
OBJECTS OF THE INVENTION
One object of the invention is to provide an economical, industrially feasible process for the production of a non-polluting calcium acetate deicing chemical.
It is a further object to produce a water-soluble calcium acetate deicing agent in the form of a coarse pellet, suitable for dispensing from standard salt-spreading equipment.
Yet another object of the invention is to produce a relatively non-friable calcium acetate deicer pellet which can be handled and dispensed with relatively little degradation to fines.
Another object is to produce a calcium acetate deicer pellet which possesses good crush strength and can be stored and handled with relatively little degradation to fines.
A further object is to provide a manufacturing process for production of calcium acetate pellets, which requires a minimum in water-evaporation energy.
Another object is to produce an acceptable calcium acetate pellet for deicing by reacting slaked lime with aqueous acetic acid, whereby there are no recycle streams, waste products or by-products with which to contend.
Other objects of the invention will become explicit as the invention is described hereinafter.
SUMMARY OF THE INVENTION
A process for manufacturing dense, hard, non-friable calcium acetate pellets of suitable size distribution for surface deicing applications. Raw material can be in the form of previously dried calcium acetate powder, or the damp product resulting from reaction of lime or slaked lime and acetic acid. In any event, the amount of water used in the pellet-making process relative to calcium acetate is critical. Too much water results in a "sticky" phase during the course of the reaction unless care is taken to add water slowly to calcium acetate. Even if this sticky phase were to be tolerated, the dried pellet from such an intermediate wet pellet is characterized by a friable surface layer comprising a substantial proportion of the total product. Such a product is unsuitable for use as a deicer.
If the water content is kept below well-defined limits, the sticky phase is completely avoided. Furthermore, the friable outer layer is no longer present in the dried material which now has all the attributes desired in an industrial deicer product.
Limits on water content vary over a well-defined range according to the particular type of calcium acetate used. Previously dried raw material requires substantially less water, and this too varies depending on the nature of that raw material.
The magnesium ion content of the particular calcium acetate used is a very critical factor in the amount of water used to make a wet pellet which leads to a suitable product. Incidentally, ceteris paribus, the inclusion of magnesium ion in the reaction batch tends to eliminate the friable coating alluded to above. On the other hand, the higher the Mg content the weaker the pellet. The magnesium content variable is compounded by the availability of natural limestones having a broad range of magnesium content. Thus, while there are preferred embodiments of the invention relative to magnesium content, other embodiments have been developed which anticipate limits on the particular limestone available for a given industrial plant.
As for the process itself, water is added in a controlled manner to the calcium acetate--whatever the source--in a rotary kiln or equivalent piece of chemical engineering hardware. The batch is continually tumbled or otherwise agitated. When the appropriate water content is reached, the wet pelletized product is sent to a drier and treated until a certain critical average residual water content is reached. Product is then cooled and sent to storage. Temperature of the pellets during drying should not exceed about 150° C., and preferably should not exceed 110° C.
A key feature of the invention is the criticality of water content of the dried product. A completely anhydrous product is to be avoided, as it becomes embrittled and is less suitable for the use intended. A water content of 0.1-0.2 mols water per mol of alkali metal acetate is preferred. Generally speaking, the more water used in pellet preparation within the allowable range, the greater the criticality of water content in the product.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
One natural crystal form of pure calcium acetate is an extremely fine and fragile needle. By slowly evaporating a saturated aqueous solution I found these needles in the lower portion of the evaporation vessel. They probably represent a definite hydrate. To the naked eye this mass of needles is indistinguishable from commercially available material known as glass wool. The upper part of the evaporation vessel invariably contains a dendritic mass of the salt. This probably represents a lower hydrate, or even the anhydrous salt. Both forms are of low density and are extremely friable.
Relatively pure calcium acetate is produced commercially for the specialty chemical market. It is extremely fine and dusty. Indeed, most commercial designations say "calcium acetate powder". Products are either designated as anhydrous or as the monohydrate, neither of which is probably correct. Other producers use the designation "Ca(Ac) 2 ·xH 2 O" where the value of x is not given; from my experience this is the more proper means of describing calcium acetate.
When I dried one commercial calcium acetate material to constant weight at 120° C. it lost the equivalent of 0.2 mols of water per mol of salt. Upon exposure of this dried sample to ambient air, 0.2 mols of water were re-sorbed. Upon heating again 0.2 mols of water were lost, etc. This indicates that the (known) monohydrate is unstable or metastable in air but that some water is sorbed in ambient atmosphere. Because this sample was an extremely fine powder, it is probable that a physisorption phenomenon is at work.
Coarse pellets of pure calcium acetate prepared according to the present invention could be dried completely to the anhydrous state. These pellets did not re-sorb water from the atmosphere, or sorbed at a rate which was not discernible within the normal testing period of approximately a week. The important point to note, however, is that when such pellets were dried (at 100° C.) to a water content of 0.1-0.2 mols H 2 O per mol of Ca(Ac) 2 , no water was lost or sorbed upon subsequent exposure to ambient air. The pellets are metastable, if not at thermodynamic equilibrium. This point provides background necessary to the understanding of the criticality of water content of the final pellet product.
Thus calcium acetate is a highly friable substance whether crystallized from aqueous solution or produced from commercial driers. Its water content is not fixed when it is exposed to ambient air, but is a consequence of its mode of preparation, probably the major determinants being its physical state of division and the prevailing vapor pressure of water. Possibly another determinant is the extent of hydrolysis during drying, and I elaborate upon this hypothesis in the ensuing discussion. In any event, no form of calcium acetate is known, regardless of its water content or state of hydration, which meets the specifications required of a surface deicer. All known forms are either very finely divided or extremely friable, and will degrade to fine powder during storage, handling and dispensing.
My initial approach to making a deicer pellet was to add enough water to a dried powder to make a pellet with plastic qualities. All the powder had to be converted in the process, a partial conversion being unacceptable. This could indeed be done, and it required about 4.5 mols of water per mol of calcium acetate. The batch invariably went through a "sticky" phase, but pellets could be produced, at least on a small scale. A major step in the process, the formation of plastic, putty-like pellets, seemed feasible on a small scale if not on an industrial scale.
A calcium acetate sample from another manufacturer was coarser, and required only 3.9 mols of water to make a plastic pellet.
Finally, a damp calcium acetate prepared freshly from chemical grade calcium hydroxide and pure acetic acid required 6.3 mols of water per mol of salt. Evidently the finer the crystals of Ca(Ac) 2 the more water is needed in the pelletizing process, a reasonable conclusion.
The production of suitable dried product from all these preparations failed, however. Drying temperature, time and prevailing water vapor pressure were varied, all to no avail. The dried pellets were always coated with a fragile layer of salt which comprised 15-20% of the total product, and this is unacceptable. Only by incorporating magnesium ion into this product could this be alleviated. But this introduces other problems to be described subsequently.
A close examination of the fragile material showed it to resemble closely the dendritic form of salt described earlier. The net water content of such products varied from 0.0 to 0.2 mols of water per mol of salt, depending upon drying temperature and time. The interior of all such pellets was more or less dense and tough, again depending upon drying parameters. It might therefore be expected that the fragile layer could be reduced or eliminated simply by increasing the ambient water pressure during drying, everything else being equal. Surprisingly, however, an increase in water pressure intensified the formation of the undesirable dendritic layer. This in turn lead to the proposition that production of pellets having an initially lower water content than heretofore would be beneficial.
Indeed, it was discovered that satisfactory pellets could be produced with as little as 3.3 mols of water per mol of freshly prepared Ca(Ac) 2 . These, when dried, were converted to tough, hard pellets with virtually no fragile layer present. Besides the achievement of the desired end result, the use of less water has two other advantages. First, a sticky phase during processing is completely avoided. Secondly, evaporation energy requirement has been reduced still further. Note that in order to convert a saturated aqueous solution of Ca(Ac) 2 to the anhydrous form about 25 mols of water must be evaporated per mol of the salt. The process of the invention affords an 87% reduction in evaporation energy compared with the solution route.
The reason for the disappearance of the dendritic phase is not known. It can be speculated that with less water present there would be a lesser degree of hydrolysis as represented by the reaction
Ca(Ac.sub.2)+2H.sub.2 O→Ca(OH).sub.2 +2HAc, or
Ca(Ac).sub.2 +H.sub.2 O→Ca(OH)Ac+HAc.
The implication is that dendrite formation is promoted by the presence of calcium hydroxide or calcium basic acetate.
Pellets are readily dried down to 0.1-0.2 mols water per mol of acetate. Straight Ca(Ac) 2 pellets are non-friable at this water level, and possess good compression or crush strength. Prolonged drying times or higher drying temperatures are required to drive out the last 0.1-0.2 mols of water. Upon driving out this water the resulting pellets are still hard, but are very brittle. A pellet dried from a precursor containing 6.3 mols of water suffers dramatically upon complete drying. Such pellets can even be crumbled between the fingers. Pellets prepared from the 3.3 mols H 2 O precursor are less sensitive upon complete dehydration. Nonetheless, it is preferable to avoid complete conversion to the anhydrous state. It could be argued that no operator would deliberately apply the extra energy required to remove that last increment of water. Yet it may happen inadvertently rather than deliberately, and the teaching is emphasized in order that an undesirable outcome can be avoided.
The mechanism of calcium acetate particle embrittlement is unknown. The data suggest again that hydrolysis during drying may be the underlying cause, with hydrolysis products migrating to grain boundaries and promoting structural weakness. A higher water content pellet would hydrolyze to a greater degree, and would lead to an expectation which is consistent with the facts. Also, higher water content could result in larger grains, lower interstitial surface area, and greater structural weakness.
The role of magnesium ion in calcium acetate must be dealt with in any practical development of an economical product. The reason is that natural limestones invariably contain magnesium to a greater or lesser degree. For example, a representative group of limestones from the continental United States have the following Mg/Ca mol ratios:
0.012, 0.015, 0.016, 0.064, 0.097, 0.215, 0.912, 0.997. Inclusion of magnesium ion in calcium acetate pellets causes a weakening of the pellet structure over the pertinent Mg/Ca mol ratio range 0-1.0. Up to a ratio of 0.1 the weakening is not serious. A ratio of 0.2 may be acceptable under some circumstances. Beyond a ratio of 0.2, compositions are possible but not preferred. From the above representative list, it appears that most limestones will be suitable for producing calcium/magnesium acetate pellets, with dolomitic limestone the outstanding exception. The latter may be used as such, and the weaker pellet produced therefrom accepted under limited circumstances, or it may be blended with low-magnesium limestones to bring the average input Mg/Ca ratio down to 0.2 or lower.
Over the Mg/Ca range 0-0.2, good pellets can be made using the same ratio of water to calcium acetate, ˜3.3. However, at Mg/Ca=1.0, this amount of water is excessive and produces a sticky intermediate. A workable mol ratio of water to calcium acetate at this Mg/Ca=1.0 level has been found experimentally to be about 3.2. Note that this amount of water is sufficient to pelletize a mol of calcium acetate to which has been added a mol of magnesium acetate.
There are four reasons for not attempting to produce only pellets with Mg/Ca mol ratios in the low range, say, of 0.012-0.016:
1. magnesium acetate is a superior deicer to calcium acetate
2. the presence of magnesium ion helps to eliminate undesirable dendrite formation in the dried pellet
3. the presence of magnesium ion assists in pellet water retention during drying and subsequent storage; this is insurance against pellet embrittlement
4. low Mg/Ca ratio raw material may be located an uneconomical shipping distance away from preferred plant sites. Obviously there is a trade-off between pellet weakening and positive attributes of magnesium ion inclusion. The invention is therefore considered operative in the Mg/Ca mol ratio range 0-1.0, with the preferred ranges 0-0.1 and 0-0.2.
As for the strength of acetic acid to be used in the process, I have discovered that stronger pellets are produced when strong acid is used for the neutralization of alkali metal oxides or hydroxides, and then this is followed by slow, controlled addition of the requisite amount of water. For example, the reaction of glacial acetic acid with calcium hydroxide proceeds as follows:
Ca(OH).sub.2 +2HAc→Ca(Ac).sub.2 +2H.sub.2 O.
All of the 2 mols of water shown in the equation is not necessarily retained in the product due to evaporation losses resulting from net positive heat of reaction. In laboratory practice, only about 1.2 mols of H 2 O are retained. Sufficient water is then added to bring the H 2 /Ca(Ac) 2 mol ratio in the final wet pellet up to 3.3. The pellet is then dried.
Alternatively, the requisite amount of water can first be blended with glacial acetic acid, with final water make-up to offset evaporation losses:
Ca(OH).sub.2 +(2HAc+1.3H.sub.2 O)→Product.
This is equivalent to using 84% aqueous acetic acid. When this is done, however, pellets can indeed be produced, but they are not quite as strong, i.e., they do not have as high a compression strength. The reason for this phenomenon may relate to the relative amount of calcium acid acetate intermediate in the two alternative approaches. This is only speculative, however, and I do not wish to be held to it.
I have found it advisable to use a slight stoichiometric excess of acetic acid when reacting with slaked lime. This assures a minimum of water-insolubles in the final product. Any acid which is truly in excess of that required overall will either be volatilized or, more likely, converted to the solid acid-acetate which is a deicer in its own right. The use of excess acid helps insure a more complete lime neutralization in the event of reaction batch inhomogeneity. I found a 5% stoichimetric excess of acid to be desirable.
Experiments were done to determine whether unslaked lime, CaO, or slaked lime, Ca(OH) 2 , is to be preferred as a raw material. Slaked lime was found to be superior, even though its cost may be higher. Lime costs are so relatively low compared to raw material acetic acid costs that use of slaked lime does not represent a significant economic penalty. The reaction of unslaked lime and acetic acid is energetic and undesirable volatilization occurs. This raises concerns over environmental pollution and worker hygiene, which can be handled, but only at increased cost and increased risk. Furthermore, uniformly sized pellets are more difficult to produce from unslaked lime, and resultant pellets are inherently weaker.
Temperature of pellets during drying was not found to be critical to the production of satisfactory product. Certainly the ceiling temperature would be below a thermal decomposition threshold, around 150° C. It is doubtful whether such temperatures could be approached without embrittling the product anyway. At a static drying oven temperature of 125° C. there were some fragile projections from otherwise hard pellets, where solution had spewed forth from pellet interiors to flash-dry on pellet surfaces. This phenomenon never occurred at oven temperatures of 100°-110° C. Since drying times depend on a number of factors such as heat flux, convection and circulation, pellet particle size and configuration of the drying equipment, no range of drying times will be claimed. As a guideline, small samples of pellets were sufficiently dried in large static drying ovens in an hour or less.
Although this invention has been described in connection with specific forms thereof, it will be appreciated by those skilled in the art that a wide variety of equivalents may be substituted for those specific elements and steps of operation shown and described herein, that certain features may be used independently of other features, and that parts may be reversed, all without departing from the spirit and the scope of this invention as defined in the appended claims.
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A process for the manufacture of calcium acetate pellets suitable for surface deicing, which comprises slow addition of water to dried calcium acetate or to calcium acetate freshly prepared from reaction of hydrated or unslaked lime with concentrated acetic acid, in an agitated vessel designed to produce pellets. Pellets are dried to a critical residual water level to avoid their embrittlement. The relative amount of water used in the pelletizing process is highly critical, and depends upon the source of calcium acetate as well as the amount of magnesium ion in the pellet formulation.
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BACKGROUND
[0001] An implanted penile prosthetic is effective in relieving erectile dysfunction in men.
[0002] An inflatable penile prosthetic typically includes a cylinder that is implanted in each corpora cavernosum of the penis, a fluid reservoir, and a pump with valve mechanisms to move fluid from the reservoir to the cylinder to create an erection in the penis. Other penile prosthetics include a malleable cylinder without inflation fluid.
[0003] Placement of a cylinder in the corpora cavernosum in a typical surgical procedure includes dilating the corpora cavernosum with a dilation tool to form an implant space sized to receive the cylinder. The cylinder is introduced into the implant space with a needle and a suture. One end of the suture is attached to the leading end of the cylinder and an opposite end of the suture is attached to a Keith needle. The Keith needle is directed through the glans penis and the cylinder is pulled distally towards the glans penis inside the corpora cavernosum.
[0004] The above-described penile prosthetics have proven effective in relieving erectile dysfunction in men. However, improvements to penile prostheses would be welcomed by surgeons and patients alike.
SUMMARY
[0005] One aspect provides a penile prosthetic including a cylinder that is implantable into a corpora cavernosum of a penis. A resorbable suture-engagement component is attached to an exterior surface of the cylinder.
[0006] One aspect provides an implantable penile prosthetic system including a pump attachable between a reservoir and an inflatable cylinder. The cylinder is configured to be placed in a corpora cavernosum of a penis. A resorbable suture-engagement component is attached to an exterior surface of the cylinder.
[0007] One aspect provides a penile prosthetic including a cylinder that is implantable into a corpora cavernosum of a penis, the cylinder having a wall that forms an exterior surface of the penile prosthetic. The wall extends from a proximal end portion to a distal end portion of the penile prosthetic. A suture-engaging component is attached to the exterior surface of the penile prosthetic. The suture-engaging component is resorbable into the tissue of the penis.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] The accompanying drawings are included to provide a further understanding of embodiments and are incorporated in and constitute a part of this specification.
[0009] The drawings illustrate embodiments and together with the description serve to explain principles of embodiments. Other embodiments and many of the intended advantages of embodiments will be readily appreciated as they become better understood by reference to the following detailed description. The elements of the drawings are not necessarily to scale relative to each other. Like reference numerals designate corresponding similar parts.
[0010] FIG. 1A is a perspective view of one embodiment of a distal portion of a penile prosthetic including a resorbable suture-engaging component.
[0011] FIG. 1B is a perspective view of one embodiment of a penile prosthetic cylinder including a resorbable suture-engaging component.
[0012] FIG. 1C is another perspective view of the embodiment of FIG. 1B in which the resorbable suture-engaging component is engaged by a suture.
[0013] FIG. 2A is an enlarged part cross-sectional view of a distal end portion of the penile prosthetic illustrated in FIG. 1A .
[0014] FIG. 2B is an enlarged end view of a distal end portion of the embodiment of FIG. 2A .
[0015] FIG. 3A is perspective view of a distal end portion of one embodiment of the suture-engaging component having a strand of tow suture attached to a ring.
[0016] FIG. 3B is an enlarged part cross-sectional view of a ring attached to a distal end portion of one embodiment of a penile prosthetic.
[0017] FIG. 3C is perspective view of a distal end portion of one embodiment of the suture-engaging component in the form of a ring with two individual strands of tow suture attached to it.
[0018] FIG. 3D is an enlarged part cross-sectional view of a ring attached to a distal end portion of one embodiment of a penile prosthetic.
[0019] FIG. 3E is an enlarged part cross-sectional view of a distal end portion of one embodiment of a penile prosthetic.
[0020] FIG. 4A is an enlarged part cross-sectional view of a distal end portion of one embodiment of a penile prosthetic engaged by a suture.
[0021] FIG. 4B is an enlarged perspective view of one embodiment of a suture-engaging component.
[0022] FIG. 5 is a perspective view of one embodiment of a penile prosthetic including a resorbable suture-engaging component and a tip component.
[0023] FIG. 6 is an enlarged part cross-sectional view of a distal end portion of one embodiment of a penile prosthetic also showing a tip component and a suture.
[0024] FIG. 7 is a perspective view of one embodiment of a penile prosthetic wherein the cylinder is malleable.
[0025] FIG. 8 is a perspective view of one embodiment of a penile prosthetic system including a pump connected between a reservoir and a cylinder, the cylinder including a resorbable suture-engaging component.
DETAILED DESCRIPTION
[0026] In the following Detailed Description, reference is made to the accompanying drawings, which form a part hereof, and in which is shown by way of illustration specific embodiments in which the invention may be practiced. In this regard, directional terminology, such as “top,” “bottom,” “front,” “back,” “leading,” “trailing,” etc., is used with reference to the orientation of the Figure(s) being described. Because components of embodiments can be positioned in a number of different orientations, the directional terminology is used for purposes of illustration and is in no way limiting. It is to be understood that other embodiments may be utilized and structural or logical changes may be made without departing from the scope of the present invention. The following detailed description, therefore, is not to be taken in a limiting sense, and the scope of the present invention is defined by the appended claims.
[0027] It is to be understood that the features of the various exemplary embodiments described herein may be combined with each other, unless specifically noted otherwise.
[0028] The term “proximal” as employed in this application means that the referenced part is situated next to or near the point of attachment or origin or a central point: as located toward a center of the human body. The term “distal” as employed in this application means that the referenced part is situated away from the point of attachment or origin or the central point: as located away from the center of the human body. A distal end is the furthest endmost location of a distal portion of a thing being described, whereas a proximal end is the nearest endmost location of a proximal portion of the thing being described. For example, the glans penis is located distal, and of the crus of the penis is located proximal relative to the male body such that a distal end of a corpora cavernosum of the patient extends about midway into the glans penis.
[0029] In this specification, “end” means endmost and “end portion” means that segment of a thing that is adjacent to and extends from the end.
[0030] In this specification, “substantially constant” in relation to a wall thickness means that the wall is configured to have equal thickness over a given area or portion except for production tolerances or acceptable variations in dimensions.
[0031] In this specification, “resorbable” characterizes a component or material that dissolves in body tissue of a patient over time. By “dissolves” is to be understood that the component or material is configured to lose its initial structural integrity and ceases to have significant coherence. In other words, once dissolved the component or material no longer provides a structural contribution to the penile prosthetic. The amount of time it takes for the component or material to dissolve is in dependency of the type of component or material and the dimensions thereof. It is useful if the component or material is dissolved at the end of a healing period after the implantation of the penile prosthetic. This will vary from patient to patient with different anatomies, but typically within 4-8 weeks post-surgery.
[0032] Experience has shown that higher satisfaction with penile prosthetics including one or two cylinders is obtained if the characteristics of the cylinder do not alter noticeably over the extent of the cylinder. This is likely because any alteration in such characteristics changes the “feel” of the erection that may be sensed by the patient or his partner during sexual activity. Improvements to penile prosthetic cylinders are possible if an end portion of the cylinder located in the distal-most part of the corpora cavernosum, adjacent the glans penis, is “filled” as much as possible to optimally expand that part of the corpora cavernosum (the front of the penis is expanded to the widest girth possible). Patient feedback indicates that optimized filling of the distal part of the corpora cavernosum provides a more natural feel of the erection. Sometimes a tip-piece or similar is utilized to optimize filling of the distal-most part of the corpora cavernosum.
[0033] Embodiments provide a penile prosthetic that is implantable into the corpora cavernosum of a penis. The penile prosthetic includes a cylinder and a resorbable suture-engaging component (RSEC). The RSEC attaches to an exterior surface of the cylinder. The RSEC is attachable to suture or a like material to assist the surgeon in implanting and adjusting the position of the cylinder in the corpora cavernosum. The RSEC is capable of subsequent biodegradation and absorption into the body of the patient, leaving the distal end portion of the cylinder unconstrained or unfettered by any form of a tip-piece. In embodiments wherein the cylinder in inflatable the unconstrained tip-piece of the cylinder expands as fully and naturally as the other portions of the cylinder to provide the user with a full and maximally expanded cylinder tip for improved girth and fullness in the area of the glans penis.
[0034] The RSEC allows the surgeon to place the cylinder in the penis with a familiar surgical approach. For example, the surgeon checks that one end of a suture (a tow suture) is engaged with the RSEC. The tow suture is led in the distal direction through the penis glans so that it is possible for the surgeon to pull the tow suture externally of the penis and move the cylinder in the distal direction, i.e. towards the distal-most part of the corpora cavernosum. The tow suture is pullable to move the cylinder in the distal direction and adjust it to optimally locate in, and fill, the distal-most part of the corpora cavernosum. The RSEC ensures that it is possible to engage the tow suture with the cylinder without providing a permanent attachment feature that undesirably changes the characteristics of the prosthetic.
[0035] Embodiments provide a penile prosthetic including a cylinder having a wall that forms an exterior surface of the penile prosthetic and extends from a proximal to a distal end of the penile prosthetic with an RSEC attached to the exterior surface.
[0036] Embodiments provide a penile prosthetic including an RSEC, which will dissolve inside the corpora cavernosum during the post-surgery healing time.
[0037] Embodiments provide a penile prosthetic that is easy to implant and adjust to optimally locate in and fill a distal-most part of the corpora cavernosum which provides an improved “feel” of the erection.
[0038] Embodiments provide an implantable penile prosthetic system including a pump attachable between a reservoir and an inflatable cylinder configured to be placed in a corpora cavernosum of a penis. An RSEC is attached to an exterior surface of the cylinder. The inflatable cylinder of the system is configured to be easily located in and fill a distal-most part of the corpora cavernosum to provide an improved “feel” of the erection.
[0039] FIG. 1A is a perspective view of one embodiment of a penile prosthetic 20 . The penile prosthetic 20 includes a cylinder 22 and a resorbable suture-engaging component (RSEC) 24 is attached to an exterior surface 26 of the cylinder 22 . In one embodiment, the RSEC 24 attaches to a distal end portion 28 of the cylinder 22 . In one embodiment, the distal end portion 28 is located between an annular shoulder 30 and a distal end 32 of the cylinder 22 . In one embodiment, the penile prosthetic 20 includes a rear tip 21 attached to the cylinder 22 and tubing 27 extending from a tubing junction 25 in the rear tip 21 , as illustrated in FIG. 1B . FIG. 1C shows another perspective view of a cylinder as in FIG. 1B in which a suture 42 is engaged with the RSEC 24 .
[0040] FIG. 2A is an enlarged partial cross-sectional view of a distal portion 23 of one embodiment of the penile prosthetic 20 having a maximum diameter D 1 of a main body portion 38 of the cylinder. In one embodiment, the RSEC includes a ring 34 attached annularly around the exterior surface 26 of the cylinder 22 and having a maximum outer diameter D 2 . In one embodiment, the ring 34 is offset a distance away from the distal end 32 of the cylinder 22 . The distance is at most three times the measurement of a maximum outer diameter D 3 of the distal end portion 28 of the cylinder 22 . In one embodiment, the distal end portion 28 tapers distally from the annular shoulder 30 in a direction towards distal end 32 , in which embodiment maximum diameter D 3 is measured where the distal end portion 28 meets annular shoulder 30 . In one embodiment, distal end portion 28 does not taper. In one embodiment, the ring 34 is attached to the exterior surface 26 at, or adjacent to, the annular shoulder 30 . In one embodiment, the ring 34 is attached to the exterior surface 26 in a location proximal to the annular shoulder 30 . In one embodiment, the ring 34 is attached to the exterior surface 26 distal to the annular shoulder 30 , i.e. on the distal end portion 28 of the cylinder 22 .
[0041] FIG. 2B is an enlarged end view of one embodiment of the distal portion 23 of the cylinder 22 as illustrated in FIG. 2A . The RSEC includes a ring 34 attached annularly around the distal end portion 28 of the cylinder 22 adjacent annular shoulder 30 . For illustration purposes, in FIG. 2B a distance or space is visible between the ring 34 and the annular shoulder 30 indicating the ring 34 being in a location proximal to the annular shoulder 30 . However, as presented above the ring 34 may also be located distal to the annular shoulder 30 in which case no distance/space would be visible between the ring 34 and the annular shoulder 30 . In one embodiment, the distal end portion 28 of the cylinder 22 has a substantially constant thickness t.
[0042] FIG. 3A is a perspective view of a distal portion 23 of one embodiment of the penile prosthetic including a ring 34 attached to the cylinder 22 proximal to a distal end portion 28 of the cylinder. In one embodiment the ring 34 is engaged with a suture strand 42 extending through a pair of slots 50 provided in the ring with approximately 180 degrees of the ring between them. In one embodiment the ring 34 has a width and a thickness and defines and inner and an outer annular surface, the inner surface engaging with the cylinder 22 .
[0043] FIG. 3B is an enlarged part cross-sectional view of a distal portion of one embodiment of the penile prosthetic 20 . In one embodiment, distal portion 23 of the cylinder 22 includes a tapering segment 36 between an annular shoulder 30 and a main body portion 38 of the cylinder 22 . In one embodiment, a proximal-most end 40 of the tapering segment 36 is located at a distance L of no more than three times the measurement of a maximum outer diameter D 3 of the distal end portion 28 of the cylinder 22 (L≦3*D3). In the embodiment of FIG. 3B , the ring 34 is attached to the exterior surface 26 on tapering segment 36 within the distance L. Also shown is a suture 42 engaged with the RSEC 24 . In one embodiment, the suture 42 includes a bifurcated portion 44 and a line portion 46 that may be connected in a knot 48 . The bifurcated portion 44 includes arms 44 a, 44 b that each engage with the RSEC 24 . In one embodiment, the RSEC 24 is configured for bonding with one end of the length of suture 42 . In one embodiment, the bond may be releasable. In one embodiment, the bond may be removable. In one embodiment, one end of the length of suture 42 is molded into engagement with the RSEC 24 . In one embodiment, the RSEC 24 includes a slot 50 that receives and engages with a suture 42 . In one embodiment, the slot 50 extends through the RSEC 24 . In the embodiment shown, the suture 42 extends through one slot 50 and through another slot 50 . One advantage is that this allows for use of a single strand of tow suture.
[0044] In one embodiment, shown in the perspective view of the distal portion 23 in FIG. 3C , one end of the length of suture 42 goes through the slot 50 and is tied on one side of the slot in a knot or ball 51 that is large enough not to slip through the slot 50 . In one embodiment, the slot 50 in the resorbable material is configured to resorb quickly enough to allow for the knot or ball 51 to be pulled through the slot 50 for removal during the surgical procedure. In one embodiment, the length of suture 42 is engaged with the RSEC 24 during manufacture of the prosthetic. In one embodiment, the RSEC 24 is configured to be engaged with a suture by the surgeon or an assistant.
[0045] FIG. 3D is an enlarged partial cross-sectional view of a distal portion of one embodiment of the penile prosthetic 20 , in which the cylinder 22 does not include an annular shoulder such that tapering segment 36 transitions smoothly into distal end portion 28 .
[0046] FIG. 3E is an enlarged part cross-sectional view of a distal portion of one embodiment of the penile prosthetic 20 . The distal end portion 28 is attached directly to the main body portion 38 and has the same diameter as the main body portion 38 at the location of attachment.
[0047] FIG. 4A is an enlarged part cross-sectional view of a distal portion 23 of one embodiment of the penile prosthetic 20 . In one embodiment, the RSEC 24 includes a tip member 52 attached to the distal end portion 28 of the cylinder 22 (indicated in phantom line). The tip member 52 is resorbable. In one embodiment, the tip member 52 is attached to the distal end portion 28 by an adhesive. In one embodiment, the exterior surface 26 of the cylinder 22 is primed with a primer coating for adhesive attachment of the RSEC 24 to the cylinder 22 . In one embodiment, a proximal end 53 of the tip member 52 abuts the annular shoulder 30 . A suture 42 is shown engaging with the tip member 52 through a slot 50 .
[0048] FIG. 4B is an enlarged perspective view of one embodiment of RSEC wherein the tip member 52 is configured as a thimble-like structure having an interior surface 54 configured to attach annularly around the distal end portion 28 of the cylinder 22 . In one embodiment, the tip member 52 attaches to the cylinder 22 around less than an entirety of an exterior surface of the distal end portion 28 . In one embodiment, the tip member 52 includes a slot 50 to receive suture 42 . Other structures for receiving the suture and attaching it to the tip member 52 are acceptable including, but not limited to, an eye or a loop protruding from an exterior surface 56 of the tip member 52 . A wall thickness of the resorbable material of the tip member 52 is one parameter for determining the time it takes before the resorbable tip member 52 loses structural integrity and eventually dissolves in the patient's body. A thicker wall will take longer time to dissolve than a thinner wall. In one embodiment, a portion of the wall of the tip member 52 adjacent to an apex 58 of the tip member has an increased material thickness to accommodate the slot 50 .
[0049] In one embodiment, the RSEC 24 is bonded to the exterior surface 26 of the cylinder 22 . In one embodiment, the RSEC is releasably bonded to the exterior surface 26 of the cylinder 22 . In one embodiment, the RSEC is removably bonded to the exterior surface 26 of the cylinder 22 .
[0050] FIG. 5 is a perspective view of one embodiment of a penile prosthetic 20 including a cylinder 22 suitable for implantation into a corpora cavernosum of a penis. An RSEC 24 configured as a ring 34 is attached to an exterior surface 26 of the cylinder 22 . In one embodiment, the penile prosthetic 20 includes a tip component 60 . In one embodiment, the tip component 60 is manufactured from a silicone material. In one embodiment, the ring 34 is attached to the cylinder 22 proximal to the tip component 60 . The tip component 60 is useful for providing additional filling of the distal-most part of the corpora cavernosum. By using a silicone material for the tip component 60 , the gain in erection “feel” due to the additional filling is achieved with a soft material. This provides a penile prosthetic with no sudden change in characteristics and with a desirable softness of the penile prosthetic in the distal part of the corpora cavernosum adjacent or contacting the glans penis to the benefit of the erection feel for both the patient and his sexual partner. In one embodiment, the cylinder 22 has a uniform wall thickness T, i.e. the cylinder wall has the same thickness over its entirety.
[0051] FIG. 6 is an enlarged part cross-sectional view of a distal portion 23 of one embodiment of a penile prosthesis 20 . In one embodiment, an RSEC including a ring 34 is attached to the cylinder 22 at the annular shoulder 30 . In one embodiment, a tip component 60 is attached to a distal end portion 28 of the cylinder 22 distal to the ring 34 . In one embodiment, a proximal end 62 of the tip component abuts the ring 34 . A suture 42 engaged with the ring 34 is shown extending in a distal direction from the ring 34 .
[0052] FIG. 7 is a perspective view of one embodiment wherein the cylinder 22 is a malleable cylinder including a silicone elastomer shaft 70 and a silver wire coil 72 configured to be placed around a silver wire core 74 with a portion of the core and coil wrapped in a polymer 76 such as urethane and at least one other portion wrapped in a polymer such as a polyester or a polyethylene terephthalate. Both segments are over-molded with a silicone rubber. It is useful to apply a hydrophilic coating to the exterior surface of the silicone rubber. Suitable malleable cylinders are available from Coloplast Corp., Minneapolis, Minnesota.
[0053] FIG. 8 is a perspective view of one embodiment of a penile prosthetic system 120 including a pump 180 connected between a liquid reservoir 182 and an inflatable cylinder 22 , the cylinder 22 including a resorbable suture-engaging component (RSEC) 24 . Tubing 184 , 186 connects the pump and the cylinders, and the pump and the reservoir, respectively. In one embodiment, the tubing 184 communicates with the inflatable cylinder 22 through a rear tip 21 . In one embodiment, the system 120 includes two individual inflatable cylinders 22 . Pressure on the pump 180 causes flow of liquid from the reservoir 182 to the cylinders 22 to create an erection in the penis. The pump 180 can include a valve activatable to release the liquid from the cylinders 22 to flow back to the reservoir 182 .
[0054] In one embodiment, the cylinder of the penile prosthetic is inflatable. Suitable materials for fabricating the inflatable cylinder include silicone, polymers such as urethanes, blends of polymers with urethane, copolymers of urethane, or the like. Suitable inflatable cylinders are available from Coloplast Corp., Minneapolis, Minn. In one embodiment, the pump and the reservoir are fabricated from material suitable for body implantation, such as silicone or the urethane-based materials described above for the cylinder.
[0055] In embodiments wherein the cylinder 22 is inflatable, using the RSEC 24 for the implantation procedure provides an additional advantage in the subsequent post healing time use of the prosthetic. The advantage includes that the distal end portion 28 is capable of the same level of expansion as the remaining part of the cylinder 22 because no permanent suture attachment feature is necessary near or at the distal end portion 28 . As the inflatable cylinder 22 is capable of expanding equally throughout its extent, the “feel” of the erection is more natural. Also, the part of the prosthetic located in the distal most part of the corpora cavernosum has the same characteristics as the rest of the prosthetic while better filling the space of the corpora cavernosum at, or adjacent to, the glans penis.
[0056] Suitable materials for the resorbable suture-engaging component include polyester urethane (PEU), polycaprolactone (PCL), polyglycolic acid (PGA), polylactic acid (PLLA), polydioxanone (PDO) and various copolymers of these.
[0057] Attachment of the RSEC 24 to the cylinder 22 may be achieved in different ways, including adhesively bond the RSEC 24 onto the cylinder by a solvent bond or using a PU adhesive in embodiments wherein the cylinder too is manufactured from a PU. In one embodiment, the RSEC 24 is directly built up from resorbable PEU liquid precursors on the PU surface of the cylinder instead of the RSEC 24 being separately provided and attached. In one embodiment, the RSEC 24 is provided as a ring 34 that is mechanically adhered by making an inner diameter of the ring 34 slightly smaller than an outer diameter of the cylinder 22 (at the desired location of attachment). By application of a solvent to the ring, the ring swells which allows it to be placed around the cylinder surface. When the solvent vaporizes the ring shrinks back down and adheres through mechanical and Van der Waals forces.
[0058] Embodiments have been described in which a penile prosthetic includes a resorbable component for engagement with a suture used to tow the penile prosthetic distally into the corpora cavernosum of a penis. The resorbable component dissolves over the post-surgery heal time and provides for the penile prosthetic to be easily locatable and adjustable without necessitating permanent suture attachment features on the prosthetic to enable the surgeon to pull the prosthetic distally. This in turn ensures a penile prosthetic with little or no influence on the characteristics over the longitudinal extent of the surface of the penile prosthetic.
[0059] Although specific embodiments have been illustrated and described herein, it will be appreciated by those of ordinary skill in the art that a variety of alternate and/or equivalent implementations may be substituted for the specific embodiments shown and described without departing from the scope of the present invention. This application is intended to cover any adaptations or variations of medical devices as discussed herein. Therefore, it is intended that this invention be limited only by the claims and the equivalents thereof.
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A method of implanting a penile prosthetic includes confirming that a tow suture is coupled with a resorbable suture-engagement component attached to an exterior surface of a cylinder. The method includes inserting the tow suture into a corpora cavernosum of a penis and pushing the tow suture through a glans of the penis and pulling on the tow suture and towing the cylinder to a distal location within the penis. The tow suture is removed from the resorbable suture-engagement component.
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FIELD OF THE INVENTION
The present invention relates to automatic mail handling systems and more particularly to methods and apparatus for merging mail streams into discrete locations on a mail sorting conveyor.
BACKGROUND OF THE INVENTION
It is common practice in the automated handling of mail documents, such as mailing envelopes and flats, to progressively feed a stack of documents from a feeder station or feeder station magazine to a shingling station and then to a singulating station. The shingling station functions to partially separate the stack of mail into an overlapping stream. The singulating station completes the process of separating individual items of mail from the overlapping stack. The separated documents are then directed from the singulating stations to sorting stations or other processing stations or devices.
Postal requirements demand that a high volume of documents be handled in a short period of time. Typically, document handling devices are required to process thousands of documents per hour with a minimum of sorting defects and product damage. Often documents of varying sizes and shapes from a number of handling stations must be merged seamlessly into sorting processes.
Typically, the first stage in the document handling process after the documents have been placed in a container or tray with the labels facing the same direction, is to load the stack of documents onto a transport mechanism, such as a conveyor belt mechanism. The transport mechanism then directs the documents into the various separators and sorting devices.
Known systems and methods typically require substantial human intervention and action to load the stacks of documents from the tray or containers onto the document transport mechanism. The operator must gather the stacks of documents and place the documents on the conveyor belt so that all the documents are in an on-edge orientation. This must be performed while taking steps to prevent the stack from falling over. Additionally, these steps are typically performed as the conveyor belt is continuously advancing the stack of documents toward the various processing stations. This is a time-intensive process and is often one of the limiting factors in achieving high-speed document processing and throughput.
The documents are typically transported to an initial processing station, such as a shingling station, prior to singulation. Shingling results in orienting either the top or bottom document in a vertical stack, or the front or lead document in an on-edge stack, so that the forward or leading edge of each successive top, bottom or front document is disposed slightly forward or laterally of the leading edge of the next adjacent document. By shingling the stacked documents, only one document at a time will enter a nip defined by singulating belts or rollers, thereby substantially reducing the possibility that more than one document at a time will be fed simultaneously through the singulating belts or rollers. The singulating belts or rollers then transport each document in an on-edge single file manner toward other sorting and processing devices.
The other sorting and processing devices are often fed from a sorting conveyor which also operates in an on-edge orientation. The sorting conveyor is often constructed of fingered belts in which a set of projecting fingers spaced at pre-determined horizontal intervals along the belt define spaces for individual documents (i.e., designated document locations). The fingers both define the spaces and function to urge the documents along the sorting conveyor to the individual sorting stations.
As the documents move along the sorting conveyor, a zip code or other indicia of destination is read from the documents. At the sorting station, the documents found between the fingers of the sorting conveyor are discharged, either pneumatically or by actuator levers, into predetermined receiving bins.
To perform their designated function, the singulating stations must discharge the singulated documents onto the sorting conveyor between the fingers of the sorting conveyor. To place the documents between the fingers of the sorting conveyors, the singulating stations must be synchronized to the movement of the fingers of the sorting conveyor. Often this requires detecting a position of an envelope and adjusting a processing speed of the singulating station to match that of the sorting conveyor. Optical sensors may be used to detect either the lead or trail edge of the mail piece so that software can adjust the speed and relative position of the output documents of the singulating station to match the finger location of the sorting conveyor.
Because of the difficulty of loading and maintaining a constant flow of documents through the singulating stations, the sorting conveyors are often fed from a number of singulating stations. Where a number of singulating stations feed the same sorting conveyor, it is often difficult to coordinate and synchronize placement of the documents into the designated document locations. A means must be provided to avoid placing two envelopes from different feeders into the same location. Where an envelope overlaps a boundary of the designated location (e.g, a finger of the fingered belt), it becomes necessary to determine whether the envelope belongs in the prior location or subsequent location. Thus a means and apparatus for reliably synchronizing document placement into the sorting conveyor would greatly improve the rate at which documents could be handled in a mail processing system.
Accordingly, it is an object of the invention to provide a means and apparatus for precisely synchronizing the output of the singulating stations to the sorting conveyor.
It is a further object to provide a means and apparatus to synchronize the individual documents of an output of the singulating station to the fingers of the sorting conveyor, instead of synchronizing the entire singulating station.
SUMMARY OF THE INVENTION
An apparatus and method is provided for synchronizing entry of an envelope from a document feeder into a designated envelope location of a mail sorting conveyor. The method includes the steps of establishing a substantially symmetric speed versus time profile around a synchronization stop point on the merge module and stopping and holding the envelope at the stop point using a deceleration rate of the speed versus time profile until receipt of a send signal from the mail sorting conveyor. In a first case, the method further includes following the speed versus time profile to accelerate to a merge speed for merging the envelope within the designated mail location of the sorting conveyor. In a second case, when the send signal arrives before the envelope reaches the stop point, holding the envelope at a constant speed across the symmetric speed versus time profile until the position of the envelope intersects an opposing side of the speed versus time profile and then following the speed versus time profile to accelerate to a merge speed for merging the envelope within the designated mail location of the sorting conveyor.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram of a mail sorting system in accordance with one embodiment of the invention;
FIG. 2 depicts two feed stations of the sorting system of FIG. 1;
FIG. 3 is a block diagram of a control system for the sorting system of FIG. 1;
FIGS. 4a and 4b depict a schematic and detailed view of a merge module of the feed stations of FIG. 2;
FIGS. 5a and 5b depict velocity/time profiles for an envelope on the merge module of FIG. 4; and
FIG. 5c is a velocity/time profile for an envelope on the merge module of FIG. 4 where a send signal is in place before the document passes the sensor.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 is a block diagram of an automatic mail sorting system 10, generally, in accordance with one embodiment of the invention. The mail sorting system 10 is of a type generally suited for handling envelopes, catalogs, or flat rectangular objects (e.g., flat boxes) no thicker than one inch (all generically referred to herein as mail or envelopes).
Included within the mail sorting system 10 are a number of automatic mail feeders 12, 14 and a number of manual feeders 16, 18. The automatic feeders 12, 14 and manual feeders 16, 18 are constructed to accept and feed mail to the sorting conveyor 20 on an individual basis and in sequence.
The automatic feeders 12, 14 may be constructed to automatically feed mail of a regular shape, size and weight. The manual feeders 16, 18 may be constructed to handle non-standard mail (e.g., oversized, overweight, non-standard size, etc.)
To feed mail to the sorting conveyor 20 in sequence, provision must be made to coordinate the activities of the feeders 12, 14, 16, 18. For example, if the first automatic feeder 14 were to fill every other designated location 32 (FIG. 2) between the fingers 36 of the sorting system, then operation of the downstream feeders 12, 16, 18 must be coordinated to prevent the downstream feeders 12, 16, 18 from also loading documents into those previously filled locations 32.
Controller 22 of the sorting conveyor 20 provides the function of coordinating the activity of the feeders 12, 14, 16, 18. The controller 22 may impose control by designating a destination of each location 32 of the sorting conveyor 20. Designating a destination of each location 32 of the sorting conveyor 20 allows the system 10 to accomplish preliminary sorting at the inputs to the sorting conveyor 20 from the feeders 12, 14, 16, 18.
Where a small number of repeating destinations 32 (e.g., four) are designated for the locations of the sorting conveyor 20, the result is a more even loading of the individual feeders 12, 14, 16, 18. For example, if the first automatic feeder 14 has a document destined for a particular geographic location, then the document could only be placed in one of four passing locations 32 of the sorting conveyor 20. The other three locations 32 then become available for use by the other feeders 12, 16, 18.
To impose control on the feeders 12, 14, 16, 18, the controller 22 simultaneously transmits a feed signal to the feeders 12, 14, 16, 18 containing an identifier of the destination of a location 32 of the sorting conveyor 20. The feed signal is transmitted as the designated location 32 passes the first feeder 14 based upon detection of a finger 36 of the sorting conveyor 20 by a photosensor 34. If the first feeder 14 has an envelope destined for that location 32, it is immediately deposited into that location 32 by the first feeder 14. A photosensor 30 detects the presence of the envelope within that location.
The detection of an envelope within a designated location 32 alerts downstream feeders 12, 16, 18 that the designated location is no longer available. Similarly, other photodetectors 24, 26, 28 (FIG. 1.) at an output of the second and later feeders 12, 16, 18 alert downstream feeders 12, 16 and the controller 22 of the presence of an envelope in a particular designated location 32.
If the location 32 is empty when it reaches the photosensor 30, then the next feeder 18 may insert an envelope into the location 32. The next feeder 18 delays insertion of its envelope from the time of detection of the feed signal. Since the second feeder 18 is further from the upstream end of the sorting conveyor 20, the time when the second feeder 18 will insert an envelope into the location 32 will be later than the time of insertion of the first feeder 14.
To deposit an envelope into a designated location 32 of the sorting conveyor 20, the feeder 12, 14, 16, 18 must synchronize insertion of the envelope with the position of the moving fingers 36 defining the boundaries of the designated location 32. The feeder 18 times the insertion of the envelope into the location 32 based upon an encoder signal provided to the feeder 12, 14, 16, 18 from the controller 22. The encoder signal from controller 22 provides a position indicator of the designated location 32 at any particular instant in time. The encoder signal may be an output of an optical encoder 56 (FIG. 3.) mechanically coupled to a shaft of the sorting conveyor, or may be a pulse train of a stepper motor used to drive the sorting conveyor 20.
The description given herein relative to the insertion of envelopes into a designated location of the sorting conveyor 20 will be provided in terms of a single designated location. It should be understood that the sorting conveyor 20 has as many designated locations 32 as fingers 36 on the belt, and the controller 22 of the sorting conveyor 20 controls each designated location in a similar manner.
FIGS. 3-5a, b and c will now be used to explain the operation of the merge module 50 (FIG. 4) and associated pitch control unit (PCU). The merge module 50 will generally be used to refer to the mechanical interface between the feed conveyors 12, 14, 16, 18 and sorting conveyor 20. The PCU will generally be used to refer to the timing and electromechanical controllers 40, 42, 44, 46 (FIG. 3.) used to merge the envelope into the designated location 32 of the sorting conveyor 20.
As shown schematically in FIGS. 4a and in more detail in 4b, the merge module 50 may be constructed of a pair of belts 52, 54 passing over a set of rollers 60, 62, 64, 66, 68, 69, 70. The spacing of a pair of entry rollers 60, 62 is designed to cause the belts 52, 54 to form a nip to grasp and hold envelopes inserted into the merge module 50 for subsequent insertion into the designated location 32 of the sorting conveyor 20. A third roller 64 maintains the pressure of one belt 52 against the other belt 54 during envelope transfer. A fourth roller 68 performs a similar function. The merge module 50 accepts an envelope 74 at a first end 72 from a singulator of the feeders 12, 14, 16, 18 and deposits the envelope into the designated location 32 of the sorting conveyor 20.
As shown in FIG. 2B, rollers 60, 62 are driven in opposite directions by a variable speed motor 48 to pull the envelope into the merge module 50 and merge it with the main conveyor 20.
To aid in merging an envelope with the main conveyor 20 in the illustrated embodiment, a photosensor 38 is provided on the merge module 50. The photosensor 38 provides position signals of a trailing edge of an envelope appropriate for establishing the precise timing necessary to merge an envelope within a designated location on the main conveyor 20.
The method used to synchronize entry of an envelope into the designated location of the main conveyor 20 will be explained by reference to FIGS. 5a, 5b and 5c. FIGS. 5a, 5b and 5c show velocity versus time profiles including deceleration and acceleration lines representing the deceleration and acceleration rates of an envelope as it moves through the merge module 50.
As shown in FIG. 5a, an envelope progresses along the merge conveyor 50 at a constant velocity V 1 (also referred to as mail infeed velocity) until being detected at time t 0 . At time t 0 , in the absence of a send signal from controller 22, the envelope decelerates at a constant deceleration rate 1 1 to a stop (shown in FIG. 5a as time t 1 ). At time t 2 , an envelope send signal is received which causes the envelope to accelerate 1 2 at a constant acceleration rate to a velocity V 1 at t 4 , until the envelope merges with the sorting conveyor 20.
In the alternative, referring to FIG. 5b, if the envelope were decelerating from velocity V 1 subsequent to t 2 and a send signal were received at time t 2 before the envelope stopped, the envelope then assumes a constant velocity, V 2 (also referred to as mail holding velocity). At time t 3 , V 2 intersects with line 1 1 , an acceleration curve originating at V=0 at t 2 , and extending at a slope from the t axis which is the same slope as deceleration line 1 2 were line 1 2 extended from V 1 , to the V=0 axis. The envelope continues to accelerate until it reaches V 1 at t 4 .
In FIG. 5c, the send signal t 2 is received from controller 22 at or before the envelope reaches t 0 . The velocity V 1 of the envelope is maintained until the envelope is deposited at the designated location 32 of the sorting conveyor 20.
Referring to FIGS. 5a, b and c, in the preferred embodiment, the areas under each curve between t 0 and t 4 will be equal. These areas represent the distance the envelope travels from the time it passes the sensor at to t 0 to the time it is ready to be inserted into the merge module at t 4 . Also the time period between t 2 and t 4 must be equal in all situations.
While the merge module 50 (FIG. 4b) is at idle, the belts 52, 54 operate at a constant speed V 1 . The envelope enters the merge module 50 at speed V 1 . As the envelope progresses through the merge module 50, a controller 40, 42, 44, 46 of the respective merge module 50 detects the envelope through the photosensor 38 at t 0 (FIG. 5a). Upon detecting the envelope, the controller 40, 42, 44, 46 decelerates the envelope to a stop at time t 1 at a constant deceleration rate 1 2 . The controller 40, 42, 44, 46 holds the envelope at the stop position between the time period t 2 minus t 1 until receipt of a send signal from the controller 22 of the main conveyor 20, which occurs at t 2 . Where the envelope is being held in the merge conveyor 50 of the first feeder 14, the receipt of the send signal causes the controller 46 of the first feeder 14 to immediately activate the merge module 50 and merge the envelope with the designated location 32 of the main conveyor 20.
Where the envelope is being held in the merge conveyor 50 of the second and later feeders 12, 16, 18, the receipt of the send signal by its respective controller unit causes the controller 44 to begin a delay period sufficient for the designated location 32 on the main conveyor 20 to move from a location proximate the main conveyor photosensor 34 (and first feeder 14) to a position proximate the second and later feeders 12, 16, 18. To determine the length of the delay, the controller 44 monitors the position feedback provided by the encoder 56 attached to a drive shaft of the main conveyor 20. The controller 44 may accomplish this by loading a distance value into a register equivalent to the distance between the photosensor 34 and the feeder 18 and decrementing the register based upon feedback signals from the encoder 56. At the appropriate moment, the controller 44 causes the merge conveyor 50 to merge the envelope into the designated location of the main conveyor 20. Similarly, the other feeder locations 12, 16 also merge envelopes from their merge conveyors 50 into the main conveyor 20 based upon their distance from the main conveyor photosensor 34.
In the alternative, the controller 22 of the main conveyor 20 may send a unique send signal to each feeder 12, 14, 16, 18. Where this technique is used, the controller 22 includes with the send signal a destination of the designated location. The local controller 40, 42, 44, 46 then determines whether the designated location is appropriate for the envelope being held in its merge module 50.
An explanation will now be provided as to the method used to merge an envelope from the merge module 50 to the main conveyor 20. For purposes of ease of explanation, it will be assumed that the envelope will be merged immediately after receipt of the send signal. While this assumption is correct only in the case of the first feeder 14, it should be recognized that the only difference is that subsequent feeders 12, 16, 18 must also delay the instant of merging until such time as the designated recipient location of the main conveyor 20 progresses to a location proximate that of feeder 12, 16, 18.
When the controller 46 receives a send signal from the controller 22 of the main conveyor 20, the controller 46 accelerates the envelope at a constant acceleration 1 1 to the constant velocity V 1 (FIG. 5a). The belts of the merge module 50 then advance the envelope from the stopped location at t 2 to the designated location 32 of the main conveyor 20. Under an embodiment of the invention, the constant velocity V 1 may be calculated to deliver the envelope to the passing designated location at the proper instant based upon the length of the merge conveyor.
Under the illustrated embodiment of FIG. 5b, it has been determined that an envelope may also be successfully merged after detection by the merge photosensor 38 without bringing an envelope to a complete stop at the stop location t 1 as designated in FIG. 5a. It has been determined that a successful merge may be accomplished by making the deceleration rate 1 1 equal the acceleration rate 1 2 , and having the envelope assume a constant velocity at the instant of receipt of the send signal.
The creation of a systematic speed versus time profile as previously set forth may be accomplished by a number of known methods using known hardware. For example, a commercially available servo device may be provided with programmable acceleration/deceleration profiles based upon the occurrence of a predetermined event (e.g., actuation of a position sensor). Alternatively, the speed/time profile may be based upon a lookup table relating velocity to time.
The present invention can be used in various other document feeder and sorter combinations. For example, a single document feeder delivering documents directly into a sorter can utilize the same inventive concepts described above and claimed herein. Also, pocket type sorters may be used in place of the finger/belt sorter described above.
Specific embodiments of a novel method and apparatus for merging envelopes into a mail sorting system according to the present invention have been described for the purpose of illustrating the manner in which the invention is made and used. It should be understood that the implementation of other variations and modifications of the invention and its various aspects will be apparent to one skilled in the art, and that the invention is not limited by the specific embodiments described. Therefore, it is contemplated to cover by the present invention any and all modifications, variations, or equivalents that fall within the true spirit and scope of the basic underlying principles disclosed and claimed herein.
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An apparatus and method of synchronizing entry of a mailpiece from a mail feeder into a designated mailpiece location of a mail sorting conveyor. The method includes the steps of establishing a symmetric speed versus time profile around a send signal. In a first case, when the mailpiece stops before receiving the send signal, the method further includes following the speed versus time profile to accelerate to a merge speed for merging the mailpiece with the designated mail location of the sorting conveyor. In a second case, when the send signal arrives before the mailpiece reaches the stop position, holding the mailpiece at a constant speed across the speed versus time profile until the position of the mailpiece intersects an opposing side of the speed versus time profile and then following the speed versus time profile to accelerate the mailpiece to a merge speed for merging the mailpiece within the designated mail location of the sorting conveyor.
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FIELD OF INVENTION
[0001] This invention relates to an electronic cigarette having L.E.D. indicators to indicate the usage of the electronic cigarette as well as memory devices for storing and generating data and charts on the usage of the electronic cigarette. The invention also relates to an improved cartomizer as well as a method of monitoring the inhalation of vapor from an electronic cigarette.
BACKGROUND TO THE INVENTION
[0002] Electronic cigarettes or e-cigarettes have recently been developed and generally comprise a battery-powered device that provides inhaled doses of nicotine or non-nicotine vapourized solutions. It is an alternative to smoking tobacco products such as cigarettes, cigars or pipes in addition to providing nicotine delivery. The vapour can also provide a flavor or physical sensation to that of inhaled tobacco smoke although no smoke or combustion is actually involved in the operation.
[0003] Generally speaking, when a user inhales an electronic cigarette, air flow is detected by a sensor which activates a heating element which vapourizes a liquid solution stored in the device. A typical e-cigarette will include a L.E.D. light cover, a battery, an atomizer and a cartridge. In some models, the cartridge and atomizer are combined in one as a cartomizer. Various prior art electronic cigarettes have been manufactured and sold.
[0004] For example, U.S. 2009/0283103 discloses a docking station for an electronic vaporizing device where the docking station includes a housing, one or more charging slots in the housing for plurality, and a spare battery for use with the electronic vaporizing device.
[0005] Yet another arrangement is shown in U.S. 2007/0074734 which refers to a smokeless lighter that includes a heater sized to accommodate a smokeable article such as a cigarette, such that a portion of the cigarette protrudes from the lighter. Optionally, a light may be used to indicate when air is drawn through the smokeless lighter.
[0006] Furthermore, U.S. 2010/0200008 shows reveals a smokeless cigarette that provides for the dispensation of vitamins to the user by way of a vitamin-infused cartridge whereby a liquid mixture of vitamins and/or botanicals are injected into a liquid-supplying bottle within the nicotine cartridge for inhalation and absorption by the user.
[0007] Moreover, U.S. Pat. No. 5,269,327 shows features an article where a tobacco flavor medium is electronically heated to evolve inhalable tobacco flavors or other components in vapor or aerosol form. The article has a plurality of charges of the tobacco flavor medium which are heated sequentially to provide individual puffs.
[0008] Yet another arrangement is shown in U.S. 2005/0016550 which illustrates an electronic cigarette having a casing with in an inhalation hole and a substantially cylindrical configuration. Pressure in a cavity filled with a liquid flavored generating medium is changed by driving an actuator to eject the flavor generating medium as droplets from a nozzle in communication with the cavity.
[0009] Another arrangement is shown in U.S. 2006/0196518 which displays a cigarette which includes a smoke mouth integer comprised with a shell, a cell, a high frequency ionizer, nicotine solution storage and its container, control circuit, a display screen, a human contact sensor, a piezoelectric supersound atomizer, a high temperature vaporization nozzle and attachments, an electro-thermal vaporization nozzle installed in the air suction end of the shell goes through an electronic control pump or valve with a measuring chamber and a liquid storage container which contains nicotine solution and is connected to the electric control pump or valve with a one-way flow valve, the control circuit plate having four export ends individually connected to the high-frequency ionizer, electric heater, pump or valve, and a display screen, a human resistance sensor and an airflow sensor are connected to the input end of the control circuit.
[0010] Yet another arrangement is shown in U.S. 2009/0095311 which relates to an aerosol electronic cigarette includes a battery assembly, an atomizer assembly and a cigarette bottle assembly and also includes a shell which is hollow and integrally formed.
[0011] Furthermore, U.S. 2010/0031968 shows an electronic smoking substitute device which includes a tube containing a reservoir containing a liquid. The liquid includes a substance to be inhaled by the user, for example, a nicotine dilution. The device also has a heating element. The heating element is a coil and is in direct contact with the reservoir. A power source is arranged to power the heating element.
[0012] Another arrangement is shown in U.S. 2007/0267031 which relates to an electronic atomizing cigarette that includes a shell and a mouthpiece. The external wall of the shell has an air inlet. An electronic circuit board, a normal pressure cavity, a sensor, a vapor-liquid separator, an atomizer, a liquid-supplying bottle are sequentially provided within the shell, wherein the electronic circuit board comprises an electronic switching circuit and a high frequency generator. A stream passage of the sensor is provided on one side of the sensor, and a negative pressure cavity is provided in the sensor. The atomizer and the liquid-supplying bottle is in contact with each other. An atomization cavity is arranged in the atomizer.
[0013] It is an object of this invention to provide and improve the electronic cigarette and method of monitoring the usage of electronic cigarettes. It is also an object of this invention to provide an improved cartomizer which is easier to construct and more efficient than that of the prior art.
[0014] It is an aspect of this invention to provide an electronic cigarette having: a power means; a heating means; a fluid; an electronic circuitry means for sensing a negative pressure in the electronic cigarette for heating the fluid to produce a vapour when a user puffs on the electronic cigarette; and an indicating means associated with the circuitry means to indicate the usage of the electronic cigarette.
[0015] In one embodiment of the invention, the heating means comprises a cartomizer having: a hollow tube shape with an inlet and outlet; a foam substrate for receiving the fluid; a fiberglass member within the atomizing cavity and in contact with the foam substrate to draw fluid into the atomizing cavity; and a heating element within the atomizing cavity and about the fiberglass member to vaporize the fluid in the atomizing chamber.
[0016] It is another aspect of the invention to provide a method of monitoring the inhalation of vapor from an electronic cigarette comprising: sensing a negative pressure in the electronic cigarette when a user puffs on the electronic cigarette; heating a fluid in the electronic cigarette upon sensing of the negative pressure so as to vaporize a portion of the fluid in the electronic cigarette; storing data regarding the usage of the electronic cigarette in a memory device; and generating charts from the memory device displaying usage of the electronic cigarette.
[0017] It is yet another aspect of this invention to provide an electronic cigarette comprising: a first hollow cylindrical member having: a battery; electronic circuitry including: a micro-controller and pressure sensor for sensing a pressure drop in the electronic cigarette; and an electronic switch activated by the micro-controller upon sensing of the pressure drop; a second hollow cylindrical member having a second longitudinal axis for coaxial alignment with the first longitudinal axis of the first hollow cylindrical member having: a cartomizer with: a hollow tube shape having an inlet and outlet; foam substrate for receiving the fluid; and a heating element for vaporizing the fluid when the microcontroller senses a pressure drop to activate the switch to heat the heating element upon a user puffing on the electronic cigarette; indicating lights for indicating the usage of the electronic cigarette, a memory device associated with the indicating lights and electronic circuitry for recording the usage of the electronic cigarette.
[0018] These and other objects and features of the invention shall now be described in relation to the following drawings:
DESCRIPTION OF THE DRAWINGS
[0019] FIG. 1 is a side plan view of the electronic cigarette.
[0020] FIG. 2 is a cross-sectional view of the first hollow cylindrical member or hollow tube 4 .
[0021] FIG. 3 is an end view of FIG. 2 .
[0022] FIG. 4 is an electronic schematic view of the electronic circuitry.
[0023] FIG. 5 shows one example of a usage chart.
[0024] FIG. 6 illustrates another example of a usage chart.
[0025] FIG. 7 is another example of a usage chart.
[0026] FIG. 8 is a side elevation view of a cartomizer.
[0027] FIG. 9 is an electronic schematic view of the indicator lights.
DETAILED DESCRIPTION OF THE INVENTION
[0028] Like parts are given like numbers throughout the figures. The drawings are not necessarily to scale but rather illustrate the invention as claimed.
[0029] FIG. 1 generally illustrates the electronic cigarette 2 which has a first hollow cylindrical member 4 disposed along the first longitudinal axis 6 and a second hollow cylindrical member 8 having a second longitudinal axis 10 for co-axial alignment with the first longitudinal axis 6 .
[0030] FIG. 2 illustrates in more detail the first hollow cylindrical member 4 which is a holding tube that houses the battery or power unit 12 and the electronic circuitry means or electronic control board 14 and the end cap 16 and a female screw terminal 18 engageable with the second hollow cylindrical member 8 in the manner to be described more fully herein.
[0031] The first hollow cylindrical member 4 includes a first end 20 which terminates at the end cap 16 . The end cap 16 can contain a LED light 22 which can be activated upon puffing on the electronic cigarette 2 in a manner to be described herein so as to simulate the lit end of a cigarette. The ends 19 and 20 are sealed with the end cap 16 and the screw terminal 18 for connecting the cartomizer 30 to be described herein.
[0032] The battery 12 can be a rechargeable battery or the like and is used to power the electronic circuitry 14 to be described herein. As stated, the battery 12 can be a single use or a rechargeable type. Recharging of the battery 12 can be accomplished through the screw terminal 18 where the threads 24 and terminal 26 provide the positive and negative terminals of the battery 12 .
[0033] FIG. 4 illustrates one embodiment of the electronic circuitry means 14 which includes a small pressure sensor 42 utilized to sense the pressure change applied by the user to the mouthpiece 70 . A microcontroller 44 along with the pressure sensor 42 is used to measure the pressure such as to perform the filtering to ensure proper signal integrity. Once a pressure change is detected the heater means 46 is enabled by way of a solid state switch (MOSFET Q 1 and Q 2 as shown).
[0034] A safety timer is enabled within the microcontroller 44 and is used to turn off the heater 46 if a safety limit of greater than a pre-selected time duration is reached. The timer is reset once the pressure returns to normal. If pressure is removed prior to the pre-selected time duration, the system will turn off the heater means 46 inside the cartomizer 30 generally immediately. As mentioned, the end cap 16 houses a LED light 16 to simulate the look of the cigarette source when activated behind the end cap 16 during the heating operation.
[0035] When a user puffs on the end of the mouthpiece 70 at the second hollow cylindrical member 8 , a pressure drop is created within the electronic cigarette 2 which is sensed by the pressure sensor and microcontroller 44 that activates the heating means 46 as previously described.
[0036] The end cap 16 is a cover that mimics the look of a tobacco cigarette. When the heater means 46 is activated, a light source shines through the end cap 16 to emulate a lit cigarette.
[0037] The screw terminal 18 provides electrical connections to the cartomizer 30 which is located within the second hollow cylindrical member 8 .
[0038] The first hollow cylindrical member 4 also includes indicating means 60 to provide an indication to the user of the approximate usage of the electronic cigarette. Each time a user applies a negative pressure to the electronic cigarette 2 by puffing on the electronic cigarette 2 , the heater means 46 is activated. Whenever the heater power is activated a counter resident in the microcontroller 44 will be activated and displayed on indicating means 60 . When the counter reaches a certain selected count such as for example 6, the next activation will be reset. The indicating means 60 may be displayed on the exterior surface of the first hollow cylindrical member 4 as shown in FIG. 1 or in the circular array of 6 LED located at the end cap 16 .
[0039] In one embodiment, the indicating means 60 is located on the exterior surface of the first hollow cylindrical member 4 and is disposed in a linear fashion. The indicating means 60 can be designed so that the indicator will only stay on when the heater is on or may in another embodiment stay on continuously.
[0040] The data relating to the usage of the electronic cigarette 2 may be stored in the memory of the electronic circuitry means 14 in a non-volatile memory so that it will not be lost once the battery is discharged.
[0041] The circuitry means 14 stores data and can generate usage logs or charts as shown in FIG. 5 . The purpose of the usage log or chart as shown in FIG. 5 is to allow the display of data that is stored in the memory. Each time the user applies negative pressure and engages the heater means 46 , the count will be logged into the non-volatile memory. A time marker will also be stamped at the same time as the count is recorded. The time stamp will be generated by means of an electronic real time clock. The usage log can be password protected to ensure confidentiality.
[0042] A separate external device can be used to interface with the electronic cigarette 2 by means of a personal computer or the like. The data can be retrievable in one embodiment by means of a link to a personal computer either by using RS323 or USB connection to the screw terminal 18
[0043] FIG. 5 shows a usage log by month which shows the puff count along the y axis and times of the day along the x axis.
[0044] FIGS. 6 and 7 illustrate other charts that can be generated. The charts can be used by a doctor advising a smoker. For example the charts will be able to graphically illustrate the frequency and time of simulated smoking, for instance that a person smokes more heavily in the morning. Furthermore a doctor will be in a better position to determine if smoking is psychological or addictive in nature and provide treatment regimes or strategies to quit smoking. In another embodiment, the charts can be used to assist in the delivery of medical THC or marijuana.
[0045] FIG. 8 illustrates a cartomizer 30 which is disposed within the second hollow cylindrical member 8 . The cartomizer 30 is generally cylindrical in shape and includes an inlet 34 and an outlet 37 , the cartridge tube 8 , as well as the foam substrate (reservoir which holds liquid) 36 . A non-flammable braided material 33 is used along with a non-flammable wick or fiberglass member 39 which has a nichrome wire 38 wrapped around it.
[0046] More specifically, the electronic cigarette 2 illustrates the cartomizer 30 which comprises a second hollow cylindrical member 8 having an inlet 34 and an outlet 37 . The foam substrate 36 receives and holds the liquid as well as defining an atomizing cavity 35 . The fiberglass member 39 is disposed in the atomizing cavity 35 and is in contact with the foam substrate 36 to draw fluid into the cavity 35 . The heating element 38 is disposed within the atomizing cavity 35 wrapped around the fiberglass member 39 to vaporize the fluid in the atomizing chamber or cavity 35 .
[0047] The fiberglass member 39 acts as a wick to draw fluid into the atomization cavity 35 . In one embodiment the fluid comprises but is not limited to propylene glycol, vegetable glycerin, or other vaporizing liquids.
[0048] FIG. 8 is a cross-sectional view of the cartomizer 30 and illustrates the cartridge tube or second hollow cylindrical member 8 as well as the foam substrate 36 . A non-flammable braided material comprising 33 is used along with a non-flammable wick or fiberglass member 39 with nichrome wire 38 wrapped around it. FIG. 8 also illustrates the foam substrate or reservoir 36 which holds the fluid.
[0049] The second hollow cylindrical member or cartridge tube 8 is used to house the members of the cartomizer 30 . The cartridge tube 8 is shaped to simulate the brown filter end of the tobacco cigarette. On the end 70 of the cartridge tube 8 is an opening 37 to allow the escape of vapour when engaged. End 70 is the mouthpiece. Another end 34 provides the electrical connections to the heater. End 34 provides a mating screw terminal to interface with the screw terminal 18 of the first hollow cylindrical member 4 .
[0050] In one embodiment, the heater means is made from a helical wrap of a heater wire 38 such as nichrome as well as a wick 39 to draw fluid from the reservoir 36 .
[0051] The foam substrate or reservoir 36 holds the fluid to be vaporized. The reservoir 36 is made of a highly porous material that is capable of holding fluids such as propylene glycol, vegetable glycerin, or other vaporizing liquids.
[0052] The foam substrate or reservoir is fire resistant.
[0053] FIG. 9 illustrates an electronic schematic that controls the LED lights associated with the indicating means 60 as previously described.
[0054] Accordingly, the electronic cigarette 2 has a power source 12 , heating means 46 , a fluid, electronic circuitry means 14 for sensing a negative pressure in the electronic cigarette 2 and for heating the fluid to produce a vapour when a user puffs on the electronic cigarette 2 ; and indicating means 60 associated with the electronic circuitry means 14 to indicate the usage of the electronic cigarette 2 . There is a memory means associated with the electronic circuitry means 14 for recording the usage of the electronic cigarette 2 . The memory means stores the time and duration of puffs. The memory means can generate charts featuring usage of the electronic cigarette 2 .
[0055] The second hollow cylindrical member 8 houses a cartomizer 30 which comprises:
(a) A generally cylindrical in shape tube and includes an inlet 34 and an outlet 37 (b) a foam substrate 36 for receiving the fluid, the foam substrate 36 defining an atomizing cavity 35 (c) a fiberglass member 39 disposed within the atomizing cavity 35 and in contact with the foam substrate 36 to draw fluid into the chamber (d) A heating element 38 disposed within the atomizing cavity 35 and wrapped about the fiberglass member 39 to vaporize the fluid in the atomizing chamber.
[0060] The invention described herein also relates to a method of monitoring the inhalation of smoke from an electronic cigarette 2 comprising:
(a) sensing a negative pressure in the electronic cigarette 2 when a user puffs on a electronic cigarette 2 ; (b) heating fluid in the electronic cigarette 2 upon sensing a negative pressure so as to vaporize a portion of the fluid in the electronic cigarette 2 (c) storing data regarding the usage of the electronic cigarette 2 in a memory device (d) Generating data from the memory device and displaying usage of the electronic cigarette 2 .
[0065] The electronic cigarette 2 as described herein illustrates:
(a) A first hollow cylindrical member 4 disposed along a first longitudinal axis 6 having a rechargeable battery, electronic circuitry which includes a microcontroller 44 along with the pressure sensor 42 for sensing a pressure drop, an electronic switch activated by the microcontroller 44 upon sensing of a pressure drop; (b) a second hollow cylindrical member 8 having a longitudinal axis 10 for co-axial alignment with the first longitudinal axis 6 wherein the second hollow cylindrical member 8 has a cartomizer and includes an inlet 34 and an outlet 37 , a foam substrate 36 for receiving the fluid, a heating element 38 for vaporizing the fluid when the microcontroller 44 and pressure sensor 42 senses a pressure drop to activate the switch to heat the heating element 38 when a user puffs on the electronic cigarette 2 ; (c) indicating lights 60 for indicating the usage of the electronic cigarette 2 ; (d) a memory device associated with the microcontroller 44 and associated with the indicating light 60 for recording the usage of the electronic cigarette 2 .
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This invention relates to an electronic cigarette having L.E.D. indicators to indicate the usage of the electronic cigarette as well as memory devices for storing and generating data and charts on the usage of the electronic cigarette. The invention also relates to an improved cartomizer as well as a method of monitoring the inhalation of smoke from an electronic cigarette.
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BACKGROUND OF THE INVENTION
This invention relates to new and improved three-dimensional embroidered articles and the method for the production of the same.
Conventionally, in producing a three-dimensional cloth article, such as a cup of a brassiere having a curved configuration or a three-dimensional embroidered article having an embroidery pattern provided thereon over the entire area, since it is difficult or impossible to embroider such three-dimensional article in its three-dimensional condition, it is usual practice first to embroider raw material cloth on a lace embroidering machine, cut the embroidered cloth into a number of small cloth pieces of specified size, and, finally, sew such small cloth pieces together to provide a desired three-dimensional configuration. In such conventional method, however, when the embroidered cloth is to be cut into small cloth pieces, it is cut to a specified size while neglecting the pattern of the embroidery without seeing to it that the cutting plane line agrees with the pattern of the embroidery. As a result, the pattern of the embroidery is irregularly cut, so that the resulting three-dimensional article has the pattern of the embroidery misaligned along the boundary line between the small cloth pieces where they are sewn together, making it impossible to construct a coordinated embroidery pattern, and, moreover, the embroidery overlaps itself along said boundary line when the small cloth pieces are sewn together, producing a thick portion, or, reversely, portions of the cloth which have no embroidery are sewn together, producing a thin portion, so that the thickness becomes non-uniform, causing the boundary line to appear more clearly. Thus, the drawback is that only a rough product can be obtained whose commercial value is low to the extent that the fact that it is formed by sewing cloth pieces together can be known at a glance.
The principal object of the present invention is to provide a method which eliminates the drawback described above and which enables a three-dimensional article to be produced relatively easily whose embroidery pattern is coordinated as a whole and has a high aesthetic value, giving an impression that the article is formed of a single piece of cloth.
SUMMARY OF THE INVENTION
According to the invention, a plurality of elemental cloth pieces each having an embroidery pattern including embroidered pattern lines extending substantially along its edge lines. Those elemental cloth pieces thus prepared are then sewn together along their embroidered edge lines to form a continuous three-dimensional cloth article having an embroidered patterns.
More specifically the method for the production of a three-dimensional embroidered article according to the invention comprises the steps of joining a plurality of paper pattern pieces together to form a three-dimensional paper pattern resembling an article to be obtained, drawing a design pattern for embroidery on the surface of said three-dimensional paper pattern including pattern lines extending substantially along seam lines which are produced as a result of said joining operation, cutting said three-dimensional paper pattern along said pattern lines again into a plurality of paper pattern pieces, preparing a plurality of cloth pieces having pattern embroidery laid thereon according to the pattern drawn on the plurality of paper pattern pieces, and sewing said plurality of cloth pieces together along the embroidery lines corresponding to said pattern lines.
The preferred embodiments of the invention are illustrated in the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
The drawing illustrates a method of producing a brassiere cup according to the present invention.
FIG. 1 is a plan view of paper pattern pieces;
FIG. 2 is a plan view of a three-dimensional paper pattern;
FIG. 3 is a plan view of the three-dimensional paper pattern having a design pattern drawn thereon;
FIG. 4 is a plan view of paper pattern pieces obtained by dividing the three-dimensional paper pattern;
FIG. 5 is a plan view of embroidered cloth pieces according to the paper pattern; and
FIG. 6 is a plan view of a completed article.
DETAILED DESCRIPTION OF THE INVENTION
Referring to FIG. 1, three planar paper pattern pieces 11, 12 and 13 are prepared as if a cup of a brassiere to be obtained were developed and cut into three parts.
The three paper pattern pieces 11, 12 and 13 are then joined together to provide a three-dimensional paper pattern 14 having a curved surface similar to the brassiere cup to be obtained, as shown in FIG. 2. The joining operation can be facilitated by employing pasting while using separate paper pieces for joining or by employing an adhesive tape. Therefore, the three-dimensional paper pattern 14 has seam lines a, b, and c resembling ridgelines formed thereon,.
Then, as shown in FIG. 3, any desired design pattern 15 is drawn on the outer surface of the three-dimensional paper pattern 14 with a writing utensil. In this connection, the design pattern 15 should be a balanced pattern as a whole including pattern lines a', b' and c' drawn substantially along the seam lines a, b, and c.
The three-dimensional paper pattern 14 is cut along the pattern lines a', b' and c' drawn substantially along said seam lines, again into three paper pattern pieces 11', 12' and 13' as shown in FIG. 4.
Then, three cloth pieces 17, 18 and 19 shown in FIG. 5 are prepared which have pattern embroidery 6 laid thereon according to the pattern drawn on said paper pattern pieces 11', 12' and 13'. More particularly, the cloth pieces 17, 18 and 19 are of substantially the same size and shape as the paper pattern pieces 11', 12' and 13' and has the embroidery 16 laid thereon on a lace embroidering machine according to the pattern 15 drawn on said paper pattern pieces.
The three cloth pieces 17, 18 and 19 are then sewn together along the embroidery lines 16a, 16b and 16c corresponding to the pattern lines a', b' and c' which are the cutting plane lines for said paper pattern. More particularly, in an operation as if the paper pattern were brought from the condition of FIG. 4 back to that of FIG. 3, the three cloth pieces 17, 18 and 19 are abutted against each other and then sewn together along the abutting lines, i.e., the embroidery lines 16a, 16b and 16c, said sewing being in the form of overcasting along the stitch direction of the embroidery lines 16a, 16b and 16c using a sewing thread similar to an embroidery thread. Thus, as shown in FIG. 6, a desired embroidered article 20, i.e., a brassiere cup, is completed.
In addition, in the three cloth pieces 17, 18 and 19 in the condition shown in FIG. 5, if the embroidery lines 16a, 16b and 16c are provided with extra edges 17', 18' and 19' outwardly extending therefrom, this is convenient for sewing since such extra edges may be removed by being cut on the back side after sewing.
The three-dimensional embroidered article 20 obtained in the manner described above has the seam lines of the three cloth pieces aligned with the embroidery lines 16a, 16b and 16c, and since the pattern embroidery 16 is not cut, the sewing condition is not discernible, especially on the front side. The pattern embroidery 16 is coordinated as a whole and beautiful, having an appearance as if it were single embroidery having a three-dimensional configuration. Moreover, the seam lines are not of non-uniform thickness, so that the feel of the article when used is good.
In addition, in the above-described method, the article 20 may be made a seen-through lace embroidered article as by making it a chemical lace by forming the cloth pieces 17, 18 and 19 of a material which is solble in chemicals.
As is apparent from the above description, according to the invention, as a result of the fact that a pattern for embroidery is drawn on a three-dimensional paper pattern with the pattern lines extending substantially along the seam lines of said paper pattern and that said pattern lines provide a basis for the cutting plane lines of the paper pattern and for the embroidery lines and sewing lines of the article, there is obtained a three-dimensional embroidered article having a beautiful curved surface as if it were a single-piece three-dimensional article having an embroidery pattern which is coordinated as a whole.
Further, the method of the present invention is applicable not only to the production of brassiere cups but also to the production of other three-dimensional articles including caps, gloves, clothing, footwear, umbrellas, pouches, furniture, sundries for home use, clothing accessories and various covers.
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The three-dimensional embroidered article is produced by preparing a plurality of elemental cloth pieces each having an embroidery pattern including pattern lines of embroidery extending substantially along its edge lines and sewing said plurality of elemental cloth pieces together along their embroidered edge lines.
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BACKGROUND OF THE INVENTION
[0001] The present invention relates to an improved and at the same time more economical process for the synthesis of 4,5-dihydro-1,3-thiazoles.
[0002] 4,5-Dihydro-1,3-thiazoles are materials that have been known for a long time and are used, inter alia, as key intermediates for the synthesis of dihydrothiazole- and thiazole-based active compounds in the agrochemical and pharmaceutical industries.
[0003] An efficient synthetic route giving very good selectivities and yields is required for the preparation of 4,5-dihydro-1,3-thiazoles. The starting materials needed for this purpose must be available on an industrial scale.
[0004] The class of 4,5-dihydro-1,3-thiazoles (I) is known and their synthesis is described, for example, in DE-A 1,964,276 and U.S. Pat. No. 3,678,064. In the synthetic route described, 1-amino-2-alkanethiols (II) are reacted with 2,2-dialkoxyalkanenitriles (III) to give the ketals (IV), which are converted by hydrolysis into the desired 4,5-dihydro-1,3-thiazoles (I). The preparation of 2,2-dialkoxyalkanenitriles (III) by the method of DE-A 1,964,276 requires an unacceptable reaction time of 40 days. An improved process described in Synthesis, 1983, 498-500, gives a yield of 83% by weight. The reaction time here is from 3 to 12 hours.
[0005] TMSCN=trimethylsilyl cyanide
[0006] In the formulas of Equations 1 and 2, R 1 , R 2 , R 3 , and R 4 are each, independently of one another, hydrogen or an organic radical having from 1 to 10 carbon atoms.
[0007] The first step in Equation 2 requires 1.57 equivalents of 1-amino-2-alkanethiol (II), which is very expensive. The disadvantage of the synthetic route described is the complicated work-up steps with isolation of the intermediates. With a view to industrial implementation, the hydrolysis using an excess of concentrated sulfuric acid (i.e., 15.5 equivalents) is particularly critical, since these large amounts of acid subsequently must be neutralized, which is highly exothermic. In addition, the neutralization forms a large quantity of salts, which is undesirable from an ecological point of view. Each step of the process described is followed by an aqueous work-up with subsequent purification. The aqueous work-up is always associated with formation of a considerable quantity of salts, which is likewise disadvantageous in an industrial process.
[0008] It was therefore an object of the invention to improve the process so that it can be implemented industrially while taking into account ecological aspects and so that the disadvantages of the earlier process are overcome. This object has been able to be achieved according to the invention.
[0009] It has surprisingly been found that the entire synthesis sequence can be carried out as a single-vessel synthesis without complicated work-up steps.
SUMMARY OF THE INVENTION
[0010] The invention accordingly provides a process for preparing 4,5-dihydro-1,3-thiazoles of formula (I)
[0011] where R 1 , R 2 , and R 3 are each, independently of one another,
[0012] hydrogen or an organic radical having from 1 to 10 carbon atoms, comprising
[0013] (1) reacting a trialkoxyalkane of the formula
[0014] where R 3 and R 4 are each, independently of one another, hydrogen or an organic radical having from 1 to 10 carbon atoms,
[0015] with CN − to form a 2,2-dialkoxyalkanenitrile of the formula
[0016] where R 3 and R 4 are defined as above,
[0017] (2) reacting the 2,2-dialkoxyalkanenitrile with an aminoalkanethiol of the formula
[0018] where R 1 and R 2 are defined as above, to form a ketal of the formula
[0019] where R 1 , R 2 , R 3 , and R 4 are defined as above, and
[0020] (3) hydrolyzing the ketal with an acid to form the 4,5-dihydro-1,3-thiazole of formula (I),
[0021] wherein the entire reaction sequence is carried out in a single vessel without isolation of intermediates.
[0022] The process of the invention can be summarized by the following reaction sequence:
DETAILED DESCRIPTION OF THE INVENTION
[0023] Examples of functional groups by which the organic radicals R 1 , R 2 , and R 3 can be substituted are alcohols and halogens. R 1 and R 2 are preferably hydrogen or alkyl groups having from 1 to 10 carbon atoms and are particularly preferably each hydrogen. R 3 is preferably an alkyl group having from 1 to 10 carbon atoms and is particularly preferably ethyl. R 4 is preferably an alkyl group having from 1 to 10 carbon atoms and is particularly preferably methyl, ethyl, or propyl.
[0024] The overall yield in, for example, the synthesis of 2-propionyl-4,5-dihydro-1,3-thiazole (formula (I) in which R 3 is C 2 H 5 ) is 40%. In addition, the amount of 1-amino-2-alkanethiol (II) was able to be reduced from 1.57 equivalent to 1.1 equivalent.
TABLE Comparison of the yields Amount Amount Overall of (II) of (III) yield Process [mol] [mol] R 1 R 2 R 3 R 4 [%] DE-A 1.57 1.0 H H C 2 H 5 C 2 H 5 16 1,964,276 Example 3 1.10 1.0 H H C 2 H 5 CH 3 40 (according to the invention)
[0025] A first advantage of the invention is the significantly better technical manageability, since a number of work-up and purification steps can be saved due to the single-vessel synthesis. Secondly, the amount of acid required was able to be reduced from 15 equivalents to 5 equivalents, which is a great advantage, particularly with a view to an industrial synthesis. The amount of salts formed in the neutralization is greatly reduced as a result.
[0026] In the process of the invention for preparing 4,5-dihydro-1,3-thiazoles of the formula (I), preference is given to heating equimolar amounts of trialkoxyalkane and cyanide (preferably from trimethylsilyl cyanide) with addition of catalytic amounts of a Lewis acid (preferably ZnCl 2 ) in a temperature range from 40 to 100° C. (preferably in a temperature range from 55 to 70° C.) for from 3 to 20 hours (preferably for a time of from 12 to 18 hours). After cooling, from 1.0 to 1.5 equivalents (preferably from 1.0 to 1.2 equivalents) of 1-amino-2-alkanethiol (II) in an organic solvent are added. As organic solvent, preference is given to using polar solvents, e.g., alcohols. The reaction mixture is then heated to from 40 to 100° C.; the reaction temperature is preferably from 60 to 80° C. The reaction time is from 3 to 20 hours, preferably from 12 to 18 hours. The solvent is preferably distilled off under reduced pressure. From 5 to 30 equivalents (preferably 5 to 15 equivalents, particularly preferably 5 to 7 equivalents) of an acid (preferably concentrated sulfuric acid) are added dropwise to the remaining reaction mixture at a temperature of from 10° C. to −10° C. (preferably from 0° C. to 5° C.). After stirring at the above-mentioned temperature for from 1 to 5 hours (preferably from 1 to 3 hours), the reaction mixture is neutralized by means of an aqueous base (preferably NaHCO 3 ). After extraction of the 4,5-dihydro-1,3-thiazole (I) into an organic phase, preferably using dichloromethane or an organic ether (e.g., diethyl ether), as solvent, the desired compounds are isolated in a yield of about 40%.
[0027] The following examples further illustrate details for the process of this invention. The invention, which is set forth in the foregoing disclosure, is not to be limited either in spirit or scope by these examples. Those skilled in the art will readily understand that known variations of the conditions of the following procedures can be used. Unless otherwise noted, all temperatures are degrees Celsius and all percentages are percentages by weight.
EXAMPLES
Example 1
2-(1,1-Dimethoxypropyl)-4,5-dihydro-1,3-thiazole (IV)—Individual Synthesis Steps
[0028] Under argon, 20.04 g of anhydrous ammonium acetate (260 mmol), 6.79 g (88 mmol) of cysteamine, and 10.33 g (80 mmol) of 2,2-dimethoxy-butyronitrile were dissolved in 80 ml of absolute methanol and refluxed for 16 h. After distilling off the solvent under reduced pressure, the reaction solution was added a little at a time to a mixture of 18.4 g of KOH, 164 ml of ice water, and 40 ml of diethyl ether. The phases were separated and the aqueous phase was extracted with diethyl ether (5×10 ml). After drying the combined organic phases over NaSO 4 and KOH pellets, the solution was evaporated and could be converted directly into 2-propionyl-4,5-dihydro-1,3-thiazole.
[0029] Crude yield: 13.89 g (73.4 mmol, 91.7%).
[0030] [0030] 1 H-NMR (400 MHz; CDCl 3 ): 0.85 (t, 3H, CH 3 ); 1.94 (q, 2H, CH 2 ); 2.27 (t, 8H, CH 2 S and OCH 3 ); 4.38 (t, 2H, CH 2 N)
Example 2
2-Propionyl-4,5-dihydro-1,3-thiazole (I)—Individual Synthesis Steps
[0031] 10.13 g (53.5 mmol) of 2-(1,1-dimethoxypropyl)thiazoline were added to 43 ml of sulfuric acid (96%) at 0 to 5° C. After stirring at this temperature for 20 min, the solution was added a little at a time to a mixture of 187 mg of NaHCO 3 , 965 mg of ice, and 64 ml of diethyl ether. After phase separation, extraction of the aqueous phase with CH 2 Cl 2 , and drying of the combined organic phases over Na 2 SO 4 , the solvent was removed under reduced pressure.
[0032] The residue was distilled using a Vigreux column to give 3.099 g (21.6 mmol, 40% yield) of product having a purity of 98% according to gas chromatography (GC).
[0033] [0033] 1 H-NMR (400 MHz; CDCl 3 ): 1.14 (t, 3H, CH 3 ); 2.95 (q, 2H, CH 2 ); 3.33 (t, 2H, CH 2 S); 4.52 (t, 2H, CH 2 N).
Example 3
Single-vessel Synthesis of 2-propionyl-4,5-dihydro-1,3-thiazole (I)—According to the Invention
[0034] 536 mg of 1,1,1-trimethoxypropane (4 mmol), 0.53 ml of trimethylsilyl cyanide (4 mmol), and 1 mg of ZnCl 2 were heated at 60° C. under argon for 16 h. 339 mg of cysteamine (4.4 mmol), 154.2 mg of ammonium acetate (2.0 mmol), and 4 ml of methanol were added and the mixture was refluxed for a further 17 h. After removing the solvent under reduced pressure, 2.043 g of sulfuric acid (96%) were added dropwise at 0 to 5° C. After stirring at this temperature for 2 h, the reaction solution was added a little at a time to a mixture of 4.7 g of NaHCO 3 (56 mmol), 75 ml of ice water, and 5 ml of diethyl ether. The aqueous phase was extracted with CH 2 Cl 2 , after which the combined organic phases were dried over NaSO 4 and evaporated under reduced pressure.
[0035] Yield (crude product): 229 mg (40%); purity according to GC: 84%.
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The present invention relates to an improved and more economical process for the synthesis of 4,5-dihydro-1,3-thiazoles carried out in a single vessel without the isolation of intermediates.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This non provisional incorporates by reference the entire contents of the prior provisional application No. 61/894,059, filed Oct. 22, 2013, and all related submittals are hereby incorporated by reference for all purposes as if fully set forth herein.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] The invention described herein may be manufactured and used by or for the Government of the United States of America for any purpose whatsoever without payment of any royalties thereon or therefor.
COPYRIGHT NOTICE
[0003] A portion of the disclosure of this document may contain materials that are subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of this document or disclosure as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever.
REFERENCE TO A SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING COMPACT DISK APPENDIX
[0004] N/A
BACKGROUND OF THE INVENTION
[0005] 1. Field of the Invention
[0006] The present invention is directed, in general, to a device and system capable of shifting at least some of the weight of a user-borne load from the user's upper body to the user's hips/pelvic area; and, more specifically, relates to a load distribution device that can be used without limitation, with a tactical vest system or protective clothing used by military and police/protective forces personnel; or, without limitation, packs, backpacks, or carriers commonly used by students, hikers, campers and other outdoor enthusiasts, or in other fields of use, without limitation, where a load may be shifted from the user's shoulders to the user's hips/pelvic area.
[0007] 2. Description of the Background Art
[0008] Military and law enforcement personnel are often required to wear tactical vests or protective clothing (hereinafter tactical vests and/or protective clothing may be referred to as a “vest” or “vests”), which are often heavy in the first instance, and made even heavier because of the incorporation or use of armor or other protective plating or materials (hereinafter either will be referred to as “Plates” or “SAPI Plates” and can include an enhanced plate variant known as ESAPI Plates). Moreover, the load that is being supported or carried by the wearer is frequently increased even further due to the addition or carrying of equipment items or gear attached to such vests.
[0009] There are many different versions of vests, many of which have been available and used by military and law enforcement personnel for years. An example of a protective vest is described in U.S. Pat. No. 6,185,731 (“U.S. Pat. No. '731”). In general, the protective vest, as described in U.S. Pat. No. '731, provides improved load-bearing features, and is adaptable to a user's tactical and ballistic characteristics. However, the “load-bearing” described in U.S. Pat. No. '731 is, in general, the provision of adaptations used to “carry” detachable elements such as supply receptacles and other auxiliary items. Therefore, while many vests are capable of carrying items that comprise a portion of the load being supported by the user, and, as described in U.S. Pat. No. '731, are securely attached to the user through a variety of means such as belts, straps, and etc., the weight of the vest and equipment is, in general, predominantly borne by the user's shoulders and back, which is a factor that can lead to physical distress, may limit mobility, and/or can cause injuries.
[0010] From another perspective, to accommodate load bearing, typical loadbearing frames used in hiking equipment (e.g., hiking packs) utilize a rigid frame-like structure which, due to the attachment of the rigid frame-like structure to a load bearing waist belt, prohibits freedom of movement such as bending over at the waist, twisting and bending side to side.
[0011] An example of a body support system is shown in, U.S. Pat. No. 8,182,439 (“U.S. Pat. No. '439”). In general, the patent states that this support system relates to support garments and in particular to body support systems that transfer back and spinal loading to the hips and legs of a user and may incorporate body armor or other load attaching features. While this system might be useful, it is Applicant's belief that the '439 system has the following limitations and/or does not meet several needs: a lack of flexibility in the vertical frame; it does not mimic natural movements of the human spine; there appears to be a limited capability to bend forward at hips and to twist at the torso, and to allow for bending side-to-side; it is worn next to the user; and it is not capable of being rapidly released and/or not capable of being easily dismantled.
[0012] An example of a device and system for supporting at least some of the weight of a heavy vest by distributing the weight off of the user's shoulders, neck, and back to at least the user's hips is described in U.S. Pat. No. 8,572,762 (“U.S. Pat. No. '762”). In general, this load distribution device comprises a back brace; a multi-element belt; and a coupling used to connect the back brace to an element of the belt, and when combined and properly oriented with a vest may form a weight distribution system.
[0013] While the device and/or system of '762 and/or '439 may provide a weight distribution and support device and system for armor vests that may redistribute weight off of the shoulders of the user, it is the Applicants' belief that there is still a present need to provide a weight redistribution device and system that provides a modular scalable vest system that includes, without limitation, a device that provides improved weight redistribution characteristics; provides the user with an improved range of motion; and provides a quick-release feature that allows a user the means to quickly separate components for tactical or other purposes.
SUMMARY OF THE INVENTION
[0014] In general, the Modular Scalable Vest (hereinafter referred to as the “MSV” or “Vest”) is the United States Marine Corps' first product of the new system of systems approach utilized for body armor design. The MSV provides a modular scalable design that replaces the multiple vest strategy with a single, tailorable system that scales from a low-visibility vest up to a level of utility and/or protective coverage similar to that of the Marine Corps “Improved Modular Tactical Vest.” A part of the present invention, and, therefore, as a part of the MSV system, is a load distribution device that enhances Warfighter mobility and reduces Warfighter fatigue by providing an improved system of distributing weight from the user's shoulders to the user's hips/pelvic area.
[0015] According to the present invention, variations of the MSV are or may be comprised of at least some, if not all, of the following items: the Fighting Vest (or Jacket), MSV Plate Carrier (“MSV PC”), the CORPS Load Distribution System (“CORPS-LDS”), the Leatherneck Guard, and the Tier-2 Protective Over Garment (“Tier-2 POG”). The various components can be removed or added to construct multiple combat suites (i.e., a group of items forming a system) of varying utility and/or armor protection levels (“APL”). The MSV, at a minimum, provides at least the same level of ballistic and fragmentation protection as the current armor systems while, without limitation, providing the important features of improved warfighter mobility and reduced physical exertion, i.e., lessened metabolic expenditure.
[0016] What could be described as a primary feature of at least one configuration of the MSV system is the present invention's load distribution device, which is named by the Applicants' as the “Central Osteoarticular Relief and Performance Structured Load Distribution System” (herein referred to as the “CORPS-LDS”). The CORPS-LDS is worn by a user to help distribute the weight of the Vest/MSV PC and equipment worn by the user from the user's shoulders to their hips and/or pelvis while not overly inhibiting the user's range of motion.
[0017] For ease of explanation, the CORPS-LDS portion of the MSV/MSV PC will now be more fully described. Specifically, according to the present invention, the CORPS-LDS is comprised of four major sections: (1) the “1775 Frame Sheet”; (2) the articulating loadbearing or load distributing spine (hereinafter referred to as the “Spine”), which, in general, can be described, and/or functions, as an external, articulating spinal column (that mimics some of the functionality of a human spine); (3) the CORPS-LDS belt attachment bracket (hereinafter referred to as the “Belt Bracket”); and (4) the “CORPS Belt.” More specifically, the 1775 Frame Sheet is designed (e.g., the 1775 Frame Sheet has sections that preferably rest on or in the area near a user's upper torso and/or shoulders) and is manufactured to provide structure and support for the CORPS-LDS in at least the area on or about the user's upper torso and/or shoulders. This design allows the invention to initiate the transfer of the load of a Vest/MSV PC including, but not limited to, the weight of Plates, soft armor, and vest materials to and/or through the Spine and, thereby, assists in facilitating the load distribution feature of the present invention. Moreover, the design of at least the upper portion of the 1775 Frame Sheet, which includes extensions that can fit within the back section of the MSV PC on or in the proximity of a user's shoulder area, can provide for the transfer of at least some of the load from the front of the Vest/MSV PC (including the Vest materials, ballistic protection plate(s) and items connected to the front of the Vest) to the Spine and the user's hips or pelvic region. In other words, the design of the 1775 Frame Sheet including these 1775 Frame Sheet extensions provide a means to, when properly adjusted, carry the load of the Vest/MSV PC from, or off of, the user's shoulders through the 1775 Frame Sheet to and through the Spine to the CORPS Belt. The CORPS-LDS 1775 Frame Sheet, in its current configuration, is made of, but is not limited to, a wood core with a carbon-fiber wood laminate. It is apparent from the design that other materials could be used for the 1775 Frame Sheet construction as long as they are preferably, but without limitation, lightweight and strong enough to bear the load of the Vest/MSV PC.
[0018] According to the present invention, the Spine is, in general, comprised of at least one “vertebra” (which, in general, may be characterized as having features of, or which essentially form, a ball-and-socket joint (or joint-like structure)). Preferably, but without limitation, each “vertebra” has three holes or apertures with one located in the center (i.e., through the center of the “ball-and-socket”), and one on each of the left and right sides of each of the “vertebra.” These apertures are primarily used for the purpose of creating open channels through the Spine when more than one “vertebra” is used, i.e., “stacked,” to form the Spine. More, specifically, each “vertebra” is preferably comprised of, but not limited to, an individual plastic and rubber component, which are preferably, but without limitation, also comprise a ball-and-socket joint structure and are flexibly joined to each other using the aforementioned ball-and-socket joint feature. And, preferably, when a number of “vertebra” are stacked on top of each other (similar to the “stacking” of human vertebra) the ball-and-socket feature in conjunction with the use of a cable or tube running through the central channel of the “vertebra” stack, and cables or tubes inserted into and running through the left and right side channels, work together to essentially provide the invention's flexible and rotatable features while still providing overall stability for the “stack” structure. More specifically, but without limitation, in one embodiment of the invention, running through the left and right side, i.e., the outer, channels of the Spine are rubber, rubber-like, semi-rigid or flexible tubes that ensure that the Spine elements, preferably comprising a stack of (i.e., more than one) “vertebra,” remain engaged and prevents over-rotation of the Spine (and/or elements comprising the Spine) while being capable of transferring load to the CORPS Belt, and, it is Applicants' belief that, at the same time, assists in providing the user with a superior rotational and bending feature and capability. Still more specifically, a preferred characteristic of the preferably, but without limitation, plastic component of each “vertebra” is that this plastic component provides compression strength and stiffness for Spine stability while only adding a minimal amount of weight, and a preferred characteristic of the, preferably, but without limitation, rubber component is that the rubber component provides the ability to compress and stretch which allows for rotation and/or twisting of the Spine assembly. Other materials with like or other beneficial properties could also be used. Regarding the central channel “cable,” a metal or other sufficiently high tensile strength cable, wire, cord, or other like item, is run through the central channel of the Spine (hereinafter referred to as the “Spinal Cord”). On the top end of the Spinal Cord is a swage, cam lock or other suitable terminator or connection device (hereinafter this terminator or connection device will be referred to as the “Spine/1775 Frame Sheet Connector” or “Upper Swage”) that, preferably, movably attaches the Spine to a, preferably, removable plastic, metal or other like material, plate bracket attached to the bottom of the 1775 Frame Sheet (hereinafter referred to as the Plate Bracket). Preferably, but without limitation, the Spinal Cord and “swage” (or other terminator) are comprised of metal in order to provide the strength needed to maintain the connection. On the bottom end of the Spinal Cord is a cam lock, swage or other suitable terminator or connection device that, preferably, movably attaches the Spine to the Belt Bracket (hereinafter this connection device will be referred to as the “Spine/Belt Bracket Connector” or “Lower Swage”) and, therefore, to the CORPS Belt (since the Belt Bracket is attached to the CORPS Belt). It should be noted that the components making up the invention may be comprised of plastic, or other suitable materials, with the caveat that the materials selected preferably provide the strength necessary at the lowest possible weight. And it also should be noted that the connection means for connecting the Spine to the 1775 Frame Sheet and/or Corps Belt can be accomplished through a variety of means. As a non-limiting example, the connection of the Spinal Cord to the 1775 Frame Sheet could be realized without making use of a Plate Bracket through the use of a channel manufactured into the 1775 Frame Sheet that would allow the insertion into and capture of the Spinal Cord and “swage” (or other terminator) in the channel. Still further, while a preferable embodiment comprising three apertures and the consequent three channels (when more than one vertebra is “stacked”) and the use of a cable or tube in each channel is described above, it should be noted that other embodiments featuring just one central aperture and consequent channel, or just two apertures (and their consequent channels) equidistant from a “vertebra” centerline (along with the use of cable(s), tubes or other flexible interconnection components) could be used in other embodiments as well.
[0019] Now back to the MSV PC. While the previously mentioned Fighting Vest (or Jacket) is or can be a base component of the MSV system, the MSV PC is the base vest for the MSV system. Furthermore, while the MSV encompasses multiple components and configurations, the MSV PC is the only component of the entire MSV suite that can accept/house the CORPS-LDS, or, in other words, the MSV can be worn in multiple configurations, but the CORPS-LDS can only be utilized when worn with the MSV PC component of the MSV. Still further, the MSV PC is worn by a user to provide fragmentation protection and to carry ballistic protection in the form of SAPI Plates. Furthermore, in order to provide load distribution, the MSV PC is capable of accepting and housing the CORPS-LDS. To provide scalable levels of armor protection, the MSV PC can be worn over the Fighting Vest (or Jacket) and/or with the Leatherneck Guard and/or the Tier-2 POG. The MSV PC can also utilize a quick release system that provides for the rapid release of the MSV PC and the CORPS-LDS from the user. Specifically, the MSV PC comprises: (1) a front ballistic panel; (2) a back ballistic panel; (3) a cummerbund assembly; and (4) a vest-release quick release system. More specifically, the front ballistic panel provides an interior pocket to house a SAPI plate and, without limitation, also provides an outer surface to which other equipment can be attached. The back ballistic panel provides an interior pocket to house a SAPI plate and/or accept the CORPS-LDS. Moreover, this back ballistic panel pocket can provide a means for the CORPS-LDS, or preferably the 1775 Frame Sheet portion of the CORPS-LDS, to be inserted and secured into the MSV PC (and the Vest). Currently, Velcro® straps are used to keep the 1775 Frame Sheet from slipping out of the MSV PC. However, other methods could be used. As a non-limiting example, arm-like structures that extend on either side of an attached Plate Bracket (which, without limitation, can preferably be used to nest a SAPI plate on the exterior surface of the 1775 Frame Sheet) could be used to “catch” on the well-known plate pocket flap that almost all armor vests have. (NOTE: The exterior surface of the 1775 Frame Sheet is the surface further away from the user when the 1775 Frame Sheet is being used or worn.) Therefore, while the operational use of the CORPS-LDS provides a means to distribute the load from the user's shoulders to their hips and/or pelvic area, it should be understood that the MSV's and/or MSV PC's flexible configurability allows the MSV and/or MSV PC to be used with or without the CORPS-LDS. Moreover, other components can be attached to the vest to provide even more protection and/or padding, and/or can be used to provide the user with additional features, as non-limiting examples these can include “side plate pockets,” and “shoulder pads.”
[0020] Preferably, the cummerbund assembly is comprised of two fabric bands constructed of a durable material, with or without ballistic materials, and is used to attach the back ballistic panel to the front ballistic panel in order to provide and maintain a secure fit to the user. Preferably, the cummerbund assembly can also be used to carry additional SAPI plates to provide additional protection to the sides of the user's abdomen. While some embodiments are described above and herein, it should be understood that a wide variety of different configurations using a wide variety of materials, and manufacturing processes can be used to make the cummerbund assembly and other elements of the invention as well.
[0021] Regarding the above-mentioned “release” systems, there are two distinct quick release systems associated with the MSV PC and the CORPS-LDS, one is well-known commercial vest-release quick release system that when actuated initiates a rapid release of the MSV PC from the user. The second is the CORPS-LDS release mechanism of this application that releases the CORPS-LDS's Spine component from the CORPS Belt component. In other words, it is preferable that: (1) The CORPS-LDS release mechanism will release with the actuation and the related operation of the vest-release quick release system allowing for the rapid release of both the MSV PC and the upper portions of the CORPS-LDS from the user; or (2) The CORPS-LDS release mechanism can be actuated to release the Spine from the CORPS Belt so that the CORPS Belt can be removed while still wearing the MSV PC or, alternatively, when the vest-release quick release system is actuated and operated the CORPS Belt can continue to be worn while allowing the user to remove the MSV PC and the upper portion of the CORPS-LDS. Moreover, in a preferable configuration the CORPS-LDS release mechanism is comprised of the components that make up the previously-described Spine/Belt Bracket Connector.
[0022] It is an aspect of the invention that the CORPS-LDS can be used to distribute the weight being carried in a manner that reduces the strain on the user's spine and back, and, thereby, may also lessen the metabolic expenditure of the user.
[0023] It is an aspect of the CORPS-LDS to provide full range of motion in the torso and shoulder through the use of a flexible spinal column that mimics the human spine. This spine allows the user to complete forward bends, side-to-side bends, torso twists, and other movements, which would be otherwise hindered by a rigid vertical support system.
[0024] It is another advantage of the CORPS-LDS that it is worn internal to the body armor system, which aids in eliminating user discomfort in the form of chafing and excess bulk. Wearing a body support system against the user increases the chance of the user experiencing chafing, hot spots, and pinching causing the user discomfort during the use of a system. By integrating the CORPS-LDS into the body armor system, the device is easier to use, more comfortable to wear since it does not rest directly against the user, and less bulky as there is no need for additional padding.
[0025] Another aspect of the CORPS-LDS is that it is capable of being rapidly released, which is useful in situations in which it would benefit the user to be unhindered such as when a user falls into water or is being stuck in a cramped space. This capability is especially pertinent if the device is to be used in military applications. Being unable to quickly release the system, especially when worn with additional weight, could cause harm or even death to a user in an emergency situation (e.g. falling in water and drowning) in which case other systems might become more of a burden than an aide. The CORPS-LDS is capable of being dismantled into its component parts allowing for easy transport and storage of the system. This also allows the user to wear only certain components of the system as best suits the user's need (e.g., just wearing the hip belt).
[0026] Moreover, the CORPS Belt utilizes a contoured shape that has a cut-out over the user's buttocks that allows the CORPS Belt to ride low on the user's hips and pelvis. This shape/design provides the following capabilities: lessens interference of the user's buttocks with the CORPS Belt, allows for weight to be transferred more evenly to the user's hips, and provides a more comfortable fit to the user. The CORPS Belt is currently comprised of fabric and ballistic materials and utilizes internal stiffeners to provide structural integrity to the belt; however, others materials and/or shapes can be used as well.
[0027] Accordingly, there are numerous applications for the MSV and/or CORPS-LDS to include military, law enforcement, recreational, sport, and industrial functions. The typical application of the CORPS-LDS is to utilize the CORPS-LDS in conjunction with a Vest/MSV PC or other similar vest, military armor, or pack system in order to distribute the weight of the system and its attachments from the user's shoulders to their hips and/or pelvic area while providing the user with superior mobility. Additional uses could include the use of the CORPS-LDS in standard recreational hiking packs. It is the Applicants' belief that integration with a hiking pack would allow such recreational user a freedom of movement and range of motion at the hips and waist not before realized when using the traditional loadbearing frames seen in today's hiking packs. In addition without limitation, the CORPS-LDS could be used, with additional add-on components and/or minor modifications, for supply personnel in industrial warehouses to assist in the handling of heavy cargo and machinery.
[0028] Additional features and advantages of the invention will be set forth in the description which follows and in part will be apparent from the description, and other parts of the disclosure of the presently described embodiments including the drawings, or may be learned from the practice of the invention. Other features and advantages of the invention will be realized and attained by the device and system particularly described in the written description, the drawings, and other portions of this disclosure. It is to be understood that the foregoing and the following detailed descriptions are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING
[0029] In order to better understand the invention and to see how the same may be carried out in practice, non-limiting preferred embodiments of the invention will now be described with reference to the accompanying drawings, in which:
[0030] FIG. 1 is a rear view of one embodiment of the CORPS-LDS in accordance with an embodiment of the present invention.
[0031] FIG. 2 a is a rear view of the 1775 Frame Sheet and Plate Bracket constructed in accordance with an embodiment of the present invention.
[0032] FIG. 2 b is a side perspective view of the 1775 Frame Sheet and Plate Bracket constructed in accordance with an embodiment of the present invention.
[0033] FIG. 3 is a side view of a Plate Bracket, Spinal Cord, and both the Spine/Belt Bracket Connector and the Spine/1775 Frame Sheet Connector in accordance with an embodiment of the invention.
[0034] FIG. 4 a are top and side views of upper and lower vertebra sections in accordance with an embodiment of the invention.
[0035] FIG. 4 b is a view of an articulating loadbearing Spine showing a Spine (i.e., a vertebra stack), the Spinal Cord, the over rotation/articulation tubes and both the Spine/Belt Bracket Connector and the Spine/1775 Frame Sheet connector in accordance with an embodiment of the invention.
[0036] FIG. 5 is a “photographic” rear view of the CORPS-LDS showing the CORPS-LDS partially disassembled in accordance with an embodiment of the present invention.
[0037] FIG. 6 a is a “photographic” rear view of the CORPS-LDS showing an assembled CORPS-LDS in accordance with an embodiment of the present invention.
[0038] FIG. 6 b is a “photographic” front view of the CORPS-LDS showing an assembled CORPS-LDS in accordance with an embodiment of the present invention.
[0039] FIG. 7 is a “photographic” rear perspective view of a top portion of a Spine showing a swage connected to the top of a Spinal Cord, and showing the Spine in close proximity to, but not connected to, the bottom of a 1775 Frame Sheet with attached Plate Bracket in accordance with one embodiment of the invention.
[0040] FIGS. 8 a , 8 b and 8 c show “photographic” rear perspective views of the operation of connecting the 1775 Frame Sheet and Spine to a Belt Bracket in accordance with an embodiment of the present invention.
[0041] FIG. 9 a is a rear view showing the back of an embodiment of the MSV comprising the MSV PC and Belt, and showing the bottom of a Spine shown attached to the Belt Bracket in accordance with an embodiment of the present invention.
[0042] FIG. 9 b is a rear view of the MSV PC showing the upper portion of the CORPS-LDS located inside the back of a MSV PC in accordance with an embodiment of the present invention.
[0043] FIG. 9 c is a rear view of the MSV PC showing a “rectangular” pocket located inside the back of a MSV PC in accordance with an embodiment of the present invention.
[0044] FIG. 9 d is a rear view of the MSV PC showing an “angled” pocket located inside the back of a MSV PC in accordance with an embodiment of the present invention.
[0045] FIG. 9 e is a front view of a MSV PC and Belt in accordance with an embodiment of the present invention.
[0046] FIG. 10 a shows a “photographic” front view of the MSV (comprising the MSV PC and Belt) in accordance with an embodiment of the present invention.
[0047] FIG. 10 b shows a “photographic” rear view of the MSV (comprising the MSV PC with CORPS-LDS, and Belt) in accordance with an embodiment of the present invention.
[0048] FIG. 11 a shows a “photographic” user's right-side view of the MSV (comprising the MSV PC with CORPS-LDS, and Belt) in accordance with an embodiment of the present invention.
[0049] FIG. 11 b shows a “photographic” user's left-side view of the MSV (comprising the MSV PC with CORPS-LDS, and Belt) in accordance with an embodiment of the present invention.
[0050] FIGS. 12 a , 12 b and 12 c show a “photographic” front, user's right side, and rear view, respectively, of a MSV PC in accordance with an embodiment of the present invention.
[0051] FIG. 13 shows a “photographic” front perspective view of a disassembled MSV PC including the front carrier, back carrier, left and right shoulder pads, left and right side plate pockets, and left and right cummerbund components in accordance with an embodiment of the present invention.
[0052] FIG. 14 is a “photographic” front perspective view of the upper portion of the MSV PC showing a vest quick release actuation mechanism handle in accordance with one embodiment of the present invention.
[0053] FIGS. 15 a and 15 b , respectively, show a “photographic” front perspective view of two commercial vest quick release systems that could be used to assist in providing the quick release feature of an embodiment of the present invention.
[0054] FIGS. 16 a , 16 b and 16 c show a “photographic” front, user's right side, and rear view, respectively, of a MSV Fighting Jacket in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0055] Certain embodiments of the present invention will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all embodiments of the invention are shown. Indeed, embodiments of the invention may be in many different forms and thus the invention should not be construed as limited to the embodiments set forth herein; rather these embodiments are provided as illustrative examples only. Furthermore, like numbers refer to like elements throughout, and the use of the abbreviation FIG. will be used to identify Figures. Furthermore, different embodiments of like items described below will be shown on different Figures with the same item number followed by one of more diacritical or accent marks (e.g., ′, ″, ′″, etc.). Moreover, the foregoing “Summary of the Invention” is incorporated into this “Detailed Description of the Invention” by reference as if set forth verbatim in this section of the application.
[0056] It will be readily understood that the components of the embodiments as generally described and illustrated in the drawings herein, could be arranged and designed in a wide variety of different configurations using a wide variety of materials, and manufactured using a variety of processes. Thus, the description of the certain described embodiments of the system, components and/or methods of the present invention, as represented by the drawings, is not intended to limit the scope of the invention, as claimed, but is merely representative of embodiments of the invention.
[0057] Referring now to the drawings, and more particularly to FIG. 1 , there is shown a non-limiting example of the CORPS-LDS 10 , which may be construed as an embodiment of the present invention device. In general, the CORPS-LDS 10 is comprised of the 1775 Frame Sheet 110 and attached Plate Bracket 115 ; the Spine 120 ; the Belt Bracket 130 ; and the CORPS Belt 150 . As to the Plate Bracket 115 shown in FIG. 1 , while it is preferable to attach a Plate Bracket 115 to the 1775 Frame Sheet 110 , another embodiment of the invention may not incorporate use of a Plate Bracket 115 , and, in which case, attachment of the Spine 120 to the 1775 Frame Sheet 110 would be implemented through alternative means or methods.
[0058] Referring now to FIGS. 2 a (& 2 b ), an embodiment (and a second embodiment shown in 2 b ) of the 1775 Frame Sheet 110 (& 110 ′) and the Plate Bracket 115 (& 115 ′) are shown. As shown in FIG. 2 b , but without limitation, this embodiment of the current design of the 1775 Frame Sheet 110 ′ is preferably contoured to match the complex curvature of Small Arms Protective Insert (SAPI)/Plate (not shown) utilized by law enforcement and military personnel to provide protection against various types of projectiles.
[0059] Also, without limitation, the 1775 Frame Sheet 110 (& 110 ′) is preferably designed to have vertical extensions (or wing sections) 111 & 112 as shown in FIG. 2 a (or 111 ′ & 112 ′ as shown in FIG. 2 b ) that extend beyond the vertical dimensions of a SAPI/Plate (not shown), and when a SAPI/Plate is nested in the Plate Bracket 115 as shown in FIG. 2 a (or 115 ′ as shown in FIG. 2 b ) the SAPI/Plate would ride on the back of the 1775 Frame Sheet 110 (& 110 ′) in an area on or near the user's back, shoulder and/or upper torso. These vertical extensions 111 & 112 (or 111 ′ & 112 ′) act as a structural means of transferring the weight of a tactical vest such as, but without limitation, the U.S. Marine Corps' Modular Scalable Vest (MSV or Vest) including the MSV Plate Carrier (MSV PC) component of the MSV, and a significant portion of the load carried by such a MSV to the 1775 Frame Sheet 110 (& 110 ′) and other elements of the invention to a user's hips and/or pelvic area. According to Applicants, the 1775 Frame Sheet 110 (& 110 ′) provides the structure and support for the CORPS-LDS 10 , at least on the user's upper torso area, and initiates the transfer of the load to the articulating external spinal column, i.e., the Spine 120 (shown in FIG. 1 ). In other words, the Frame Sheet 110 (& 110 ′) serves as an interface between the user and the load borne by the user when transferring the weight from the user's shoulders to a user's hips and/or pelvic area. Moreover, in one preferred embodiment of the invention, the percentage weight transfer is adjustable, and, as a non-limiting example, 20% (more or less) of the weight could be on or carried by the user's shoulders and the remaining 80% (less or more) of the weight could be essentially transferred or carried by a user's hips and/or pelvic region. Moreover, the MSV and the MSV PC are designed so that the MSV and/or MSV PC may be used with or without the CORPS-LDS (i.e., the CORPS-LDS is designed to be a removable feature vice being fixed and required).
[0060] However, it also should be noted that the shape of the 1775 Frame Sheet 110 (& 110 ′) is not limited to the contour and profile of the SAPI plate and can take on varying ergonomic forms to match the contour of a user's upper torso profile and/or the profile of the load that will be carried by the CORPS-LDS 10 and the 1775 Frame Sheet 110 (& 110 ′).
[0061] The 1775 Frame Sheet 110 (& 110 ′ and the other 1775 Frame Sheet embodiments shown on several of the other Figures) is currently constructed using a maple wood core with a carbon fiber laminate. The current construction process is similar to that used for typical ski and snowboard designs/products, and it is currently believed to provide the present invention with sufficient durability at the lightest weight. Preferably, without limitation, other material options for the 1775 Frame Sheet 110 (& 110 ′ (and the other embodiments of the 1775 Frame Sheet)) can include the use of plastic, metal or composites, and could utilize other suitable construction/manufacturing processes as needed for the application/use.
[0062] Now while referring to FIGS. 2 a , 2 b , 9 c and 9 d , and while a SAPI plate is not shown in these FIGs., the current design of the 1775 Frame Sheet 110 (or 110 ′) allows for a SAPI plate to “nest” in a Plate Bracket 115 (or 115 ′), which, in turn, allows a SAPI plate to ride on or is adjoining to the outer surface of the 1775 Frame Sheet 110 (or 110 ′) (i.e., when being worn the 1775 Frame Sheet outer surface is the surface furthest away from a user). Preferably when used with a MSV PC (and/or MSV), the 1775 Frame Sheet 110 (& 110 ′) resides inside the back SAPI plate pocket (as shown in FIG. 9 c as 550 ′, and in FIG. 9 d as 550 ″) of the back of the MSV PC, which, as preferably shown, is designed or can be modified to accommodate the 1775 Frame Sheet 110 (& 110 ′). Preferably, as shown in FIG. 9 b , 9 c and/or 9 d , the upper portion of CORPS-LDS 10 is inserted into a “pocket” 550 ′ (or 550 ″) that is sewn or otherwise attached to the interior side of the back of the MSV PC 500 ′, it should be realized, however, that attachment of the CORP-LDS 10 with a MSV PC 500 ′ is not limited to such a pocket and could be accomplished through other means. Moreover, the Plate Bracket 115 (or 115 ′) at the bottom of the 1775 Frame Sheet 110 (or 110 ′) is preferably rigidly attached to the 1775 Frame Sheet, and provides the connection point to which the Spine 120 attaches to the 1775 Frame Sheet. As previously described, an alternative, non-limiting, Plate Bracket design could incorporate the use of a modification to secure the 1775 Frame Sheet 110 (or 110 ′) inside the well-known plate pocket flap that almost all armor vests (including the MSV PC) have. For example, the use of arm-like structures (not shown) extending on either side of a Plate Bracket could be used to “catch” on the well-known plate pocket flap. Currently, the Plate Bracket 115 (or 115 ′) is riveted onto the 1775 Frame Sheet 110 (or 110 ′); however, other attachment means such as an adhesive, screws, or even making it an integral part of the 1775 Frame Sheet 110 (or 110 ′) itself could be used. In another non-limiting embodiment, the Plate Bracket 115 (or 115 ′) is not required and/or used, and the CORPS-LDS including its Spine connection can still be worn by a user. In other words, in this alternate embodiment, the Spine is attached to the 1775 Frame Sheet using a different (non-plate) bracket or other similar means that would still provide the articulation function of the Spine, and, thereby, still allow for the inventive load distribution function to be provided by the CORPS-LDS when the CORPS-LDS is worn without the use of a Plate Bracket or ballistic protection plate.
[0063] Referring now to FIG. 3 and FIG. 1 , FIG. 3 shows a non-limiting embodiment of Plate Bracket 115 ″″ and the connection system 101 used to connect the Spine 120 (shown in FIG. 1 ) between the 1775 Frame Sheet 110 and the Belt Bracket 130 (both of which are shown in FIG. 1 ). As previously described, and preferably, on the top end of the Spinal Cord 210 is an upper swage 160 ′ (hereinafter referred to as the “Spine/1775 Frame Sheet Connector” or “Upper Swage”) that, preferably, movably, attaches the Spine 120 to the Plate Bracket 115 , which is attached to the bottom of the 1775 Frame Sheet 110 . Preferably, on the bottom end of the Spinal Cord 210 is a lower swage 165 (hereinafter referred to as the “Lower Swage”). Preferably, the Lower Swage 165 movably, attaches the Spine 120 to the Belt Bracket 130 , and, therefore, the CORPS Belt 150 (since the Belt Bracket 130 is attached to the CORPS Belt 150 ) through the nesting of the Lower Swage 165 into, and use of, the locking device 220 , (note that the locking device 220 may hereinafter be referred to as the CORPS-LDS “quick-release” mechanism). As shown in FIG. 3 , the “quick-release” mechanism 220 is preferably, but without limitation, comprised of a cam-type locking device. Preferably, besides using the well-known operational features of “cam-type” locking devices, the locking device 220 and the Lower Swage 165 portion of the connection system 101 both allow or provide for the attachment of the Spine 120 to the Belt Bracket 115 and also provides a “quick-release” capability, i.e., rotating the locking device 220 away from the Belt Bracket 130 or, in other words “opening” the locking device 220 will allow the separation of the CORPS Belt 150 and Belt Bracket 130 from the Spine 120 and 1775 Frame Sheet 110 . Moreover, the Spine 120 and 1775 Frame Sheet 110 can also be quickly released from the CORPS Belt and Belt Bracket by utilizing the well-known Vest (or MSV PC) quick-release feature, in which case, as the quick-release feature is actuated the MSV PC would fall away from the user, and consequently, the Lower Swage 165 will slide out of, and, therefore, disengage from the Belt Bracket 130 . Or, as previously described, the CORPS-LDS quick-release feature can be operated manually by opening, i.e., rotating the locking device into a release position; thereby, disengaging, the locking device 220 from the Belt Bracket 130 . It should be understood, that while use of a cam type locking device is preferable other suitable devices or components can be used as well. Moreover, it should be noted that these release systems are designed to operate without interference even while the user is in a vertical orientation.
[0064] Preferably, but without limitation, the Spinal Cord is constructed of a metal cable; the Spine/1775 Frame Sheet Connector (Upper Swage) and the Lower Swage are both currently manufactured from metal, and the locking device is currently manufactured from a ruggedized composite plastic through which one end of the Spinal Cord is fed and attaches to the locking device through the use of the Lower Swage (or through the use of a screw or other suitable cable terminator). While the use of a swage type device is described above, it should be noted that, without limitation, other cable end terminators and suitable connection devices can be used. Moreover, while plastic or metallic components are preferable, it should be realized that other suitable alternative materials of sufficient load bearing and operational capabilities can be substituted for any or all of the items of the connection system 101 .
[0065] According to the invention, the design of the Spine 120 (and its other embodiments) allows the user to bend and twist at the waist, i.e., in order to make or complete various movements. When in the upright standing, walking or running position, a portion of the weight of the CORPS-LDS 10 (as shown in FIG. 1 ) and any ancillary equipment borne by the user is distributed from the Frame Sheet 110 through Spine 120 to the CORPS Belt 150 (as shown in FIG. 1 ).
[0066] Now additionally referring to FIGS. 4 a and 4 b , the Spine's 120 vertical dimension (or height) is, without limitation, adjustable by varying the number of “vertebra” 125 used, or by using “vertebra” of differing vertical dimensions, i.e., differing heights. The “vertebra” 125 is preferably comprised of rigid 121 and semi-rigid 126 vertebra components or elements. Moreover, the vertical orientation of the Spine 120 with respect to a user's back can also be raised or lowered through the use of separate adjustment means associated with the Plate Bracket 115 and/or the Belt Bracket 130 , e.g., this adjustment can be accomplished through the use of vertically adjustable connectors between the Spine 120 and 1775 Frame Sheet 110 and/or the Spine 120 and CORPS Belt/Belt Bracket 130 connection.
[0067] More specifically, the preferable configuration of the Spine 120 is comprised of at least one vertebra 125 , which itself is comprised of at least one pair of components, i.e., an upper vertebra component 121 and a lower vertebra component 126 . Each vertebra component 121 and 126 , respectively, has a ball and socket-like joint configuration comprised of an upper vertebra component “ball” 124 , a lower vertebra component “ball” 127 , an upper vertebra component “socket” 122 , and a lower vertebra component “socket” 123 . It is readily apparent that the “ball” 124 of the upper vertebra component 121 would “fit” or “nest” in the “socket” 123 of the lower vertebra component 126 , and that the “ball” 127 of a lower vertebra component 126 would “fit” or “nest” in the “socket” 122 of a upper vertebra component 121 . Consequently, each “vertebra” 125 is comprised of, and benefits from the features of, this combination of an upper vertebra component 121 and a lower vertebra component 126 .
[0068] To provide the capability of movable connecting a stack of “vertebra” together, primarily, but without limitation, for the purpose of forming the Spine 120 , each upper vertebra component 121 and each lower vertebra component 126 is designed and manufactured with a hole or aperture running through the center 117 a of the upper vertebra component 121 , and a hole or aperture running through the center 117 b of the lower vertebra component 126 ; a hole or aperture running through the left side 118 a and the right side 119 a of the upper vertebra component 121 ; and a hole or aperture running through the left side 118 b and the right side 119 b of the lower vertebra component 126 , respectively. Thereby, the aligning of these holes or apertures forms three (i.e., center, left, and right) open channels through each of a stack of vertebra 125 , or in other words, through the Spine 120 . The Spinal Cord 210 runs through the center channel of the Spine. Furthermore, preferably running through or inserted into the left and right side channels of the Spine 120 are rubber or rubber-like “tubes” 128 & 129 , which are used to assist in ensuring the upper vertebra component 121 , the lower vertebra component 126 , the vertebra 125 itself and the vertebra stack, i.e., the Spine 120 , remain substantially engaged, and to prevent the over-rotation and/or over-bending of the Spine 120 . While it is preferable that the left tube 128 and the right tube 129 are inserted using a press-fit process, a less restrictive insertion method may be used as well. Moreover, while it is preferable that rubber or rubber-like materials are used for the tubes 128 & 129 , it should be realized, but without limitation, that other flexible or semi-rigid materials including cables akin to the Spinal Cord may be used as well. Moreover, other embodiments of the Spine could comprise just the central channel, or just the left and right channels—which would require the use of a different connection system including, without limitation, a two-to-one interface, i.e., the two tubes or cables running through the left and right channels could be connected to the left and rights sides of a lower end of an interface bracket that utilizes a single, center cable that would be capable of connecting the interface bracket to the Plate Bracket.
[0069] Referring now to FIG. 5 , an “exploded” rear view of an embodiment of the CORPS-LDS 10 ′ and its component parts ( 110 ″, 115 ″, 120 ′, 130 ″, 150 ′, and 220 ′) are shown. And, referring now to FIGS. 6 a and 6 b , the rear view and front view, respectively, of an assembled CORPS-LDS 10 ′ are shown.
[0070] Referring now to FIG. 7 , a photographic view of components of an embodiment of the CORPS-LDS is shown. More specifically, FIG. 7 shows an embodiment of the top of a Spine 120 ″ and Upper Swage (Spine/1775 Frame Sheet Connector) 160 ″, and the bottom of the 1775 Frame Sheet 110 ′ and the Plate Bracket 115 ′″ while the Spine and Frame Sheet are separated from each other. In this embodiment, the Spine attachment mechanism (which is shown as centrally located on the Plate Bracket) when in the unlocked or open position will allow for the Upper Swage 160 ″ to be inserted into the attachment mechanism portion of the Plate Bracket 115 ′″, which can then be locked or closed in order to movably attach the Spine to the 1775 Frame Sheet, and while still providing or allowing the Spine to rotate and otherwise move relative to the 1775 Frame Sheet and Plate Bracket.
[0071] Referring now to FIGS. 8 a , 8 b , and 8 c , these FIGs. show more detail regarding the attachment of an embodiment of the Spine 120 ″ to an embodiment of the Belt Bracket 130 ″. More specifically, the upper portion of FIG. 11 a shows the bottom of the Spine, and also shows the ends of the tubes running through the Spine, and the locking device 220 ″ (and also shows the locking device 220 ″ connected to the Lower Swage 165 ′). Furthermore, the lower portion of FIG. 8 a shows an embodiment of the Belt Bracket 130 ′″, which also shows the integral locking mechanism for locking the locking device 220 ″ to the Belt Bracket. Referring now to FIG. 8 b , shown is the locking device 220 ″ inserted into the locking mechanism in the open or unlocked position. To complete the attachment process, the locking device 220 ″ is rotated into the closed or locked position as shown in FIG. 8 c . It should be noted that embodiments of the Belt Bracket are designed so that the locking mechanism portion of the Belt Bracket can vertically move for up to several inches relative to the Belt Bracket; therefore, once the locking device 220 ″ is locked the CORPS-LDS and the user are provided with an enhanced bending movement feature.
[0072] Referring now to FIGS. 9 a and 9 b , each of these FIGs. shows a rear view of an embodiment of a MSV (MSV PC) 500 . And FIG. 9 b , additionally shows not only the visible portions of the CORPS-LDS when worn with the MSV-PC 500 , but it also shows the hidden (or cut-away) view portion of the CORPS-LDS as well. More specifically, this cut-away view shows how the remainder of a complete CORPS-LDS 10 , i.e., the upper portion of the Spine 120 , the Plate Bracket 115 , and the 1775 Frame Sheet 110 , would be located within the MSV PC 500 when the MSV PC 500 and CORPS-LDS 10 is worn by a user. Furthermore, the front view of an embodiment of the MSV PC 500 and Corps Belt 150 ′ is shown in FIG. 9 e.
[0073] Referring now to FIGS. 10 a and 10 b , these FIGs. show the front view and rear view, respectively, of an embodiment of the MSV 1000 including the MSV PC 500 ′″, the Corps Belt 150 ′ and the other components of the lower portion of the CORPS-LDS (shown in FIG. 10 b ).
[0074] Referring now to FIGS. 11 a & 11 b , a user's right side and user's left side photographic views of an embodiment of the MSV-PC 500 ′″, CORPS Belt 150 ′ and other portions of the CORPS-LDS are respectively shown. Furthermore, a user's front side, right side, and rear side photographic views of an embodiment of the MSV-PC 500 ′″ are respectively shown in FIGS. 12 , 12 b , and 12 c.
[0075] Referring now to FIG. 13 , an “exploded” view of an embodiment of a MSV-PC is shown. More specifically, FIG. 13 shows a Front Carrier 600 , a Back Carrier 605 , right and left Shoulder Pads ( 620 a and 620 b , respectively), right and left Side Plate Carriers ( 615 a and 615 b , respectively), and right and left Cummerbund components ( 610 a and 610 b , respectively) that when connected form the Cummerbund 610 .
[0076] Referring now to FIGS. 14 , 15 a and 15 b , embodiments of vest quick-release components are shown. Referring first to FIGS. 15 a and 15 b , each respectively show an embodiment of commercially available vest quick-release systems 710 ′ and 710 ″ of the type capable of being used to provide the vest quick-release feature of the present system. It is well known that each of the cables of such systems (e.g., 715 and/or 725 ) respectively attach to the buckles shown on the Front Carrier 600 (shown on FIG. 14 ), and when the tabs 711 and 721 (shown in FIGS. 15 a and 15 b respectively) are operated the cables cause the buckles to open, which allows the separation of the Front Carrier 600 from the Back Carrier 605 (both of which are shown on FIG. 13 ). Referring now to FIG. 14 , shown is an improved vest quick-release handle 700 that is attached to the tab 711 or 721 shown in FIGS. 15 a and 15 b respectively. This handle 700 is designed to ergonomically make the operation of the vest quick-release system easier and/or more efficient.
[0077] Referring now to FIGS. 16 a , 16 b , and 16 c , a user's front side, right side, and rear side photographic views are respectively shown of an embodiment of a MSV Fighting Jacket 800 . While the MSV-PC is the base vest for the MSV, as previously stated, the MSV is highly configurable and scalable. With this in mind, the MSV Fighting Jacket 800 ″ is a component that can be utilized in an embodiment of the MSV, preferably in an embodiment in which the Fighting Jacket 800 ″ is worn under a MSV-PC. Moreover, the Fighting Jacket 800 ″ can carry front and rear SAPI Plates to provide small arms protection to the user.
[0078] Finally, it will be apparent to those skilled in the art of load bearing equipment design and construction, and/or other related fields that many other modifications and/or substitutions can be made to the foregoing embodiments without departing from the spirit and scope of the present invention. The current embodiments of the present invention are described herein. However, it should be understood that the best means, method or implementation for carrying out the invention herein described is by way of illustration and not by way of limitation. Therefore, it is intended that the scope of the present invention includes all of the modifications that incorporate its principal design features, and that the scope and limitations of the present invention should be determined by the scope of the appended claims and their equivalents.
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The present invention is a loadbearing device known by the Applicants' as the “Central Osteoarticular Relief and Performance Structured Load Distribution System” (“CORPS-LDS”), which is worn by a user to help distribute the weight of a load being carried or borne by the user. More specifically, the weight is substantially shifted from the user's shoulders to their hips while not overly inhibiting the user's range of motion. Furthermore, it is an aspect of the CORPS-LDS to distribute the weight being carried in a manner that reduces the strain on the spine and back while lessening the metabolic expenditure of the user. Moreover, the present invention is a protective vest system that utilizes the present invention's CORPS-LDS.
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CROSS-REFERENCES TO RELATED APPLICATIONS
This application claims priority to U.S. patent application Ser. No. 61/078,219 entitled “Apparatus, System, and Method for Automobile Protection Device” and filed on Jul. 3, 2008 for Craig Kimball, which is incorporated herein by reference.
BACKGROUND
1. Field of the Invention
This invention relates to automotive exterior protection, and more particularly relates to detachable and reusable devices that protect the exterior of an automobile from side impacts from adjacently parked cars.
2. Description of the Related Art
The automobile protection devices in this field typically provide a protective buffer for side impacts for stationary automobiles. When an automobile is stationary, it can often be impacted by objects to the sides of that automobile. The sides of an automobile are most often not adequately protected by the front and rear bumpers. Contacts from other cars in a parking lot can often scar or dent the surface of the automobile or remove paint from the automobile surface. In addition to damaging the automobile aesthetically, this damage can cause permanent body damage as protective coatings are removed from the automobile surface and rusting can occur.
Certain automobiles contain built-in buffers along the side of the automobile, but these are often insufficient to protect against the impacts that the automobile receives. These built-in buffers are also often placed too high or too low on the automobile to protect the automobile body where the protection is needed. These buffers also do not extend far enough from the surface of the automobile to stop objects before those objects impact other portions of the automobile. Scratches and scars on these built-in buffers are still aesthetically damaging to the automobile as the buffer is part of the exterior of the automobile. In addition, there are many automobiles in which the styling does not include room for a built-in buffer to be places on the exterior of the automobile.
Other inventions in this field offer protection from scratches and dents, but can be difficult and clumsy to install and use. Several examples from the prior art utilize door clamps or straps which take time and effort to put in place every time the user wishes to protect his car from parking lot dents. It could be argued that even though difficult to install, the protection panels can just be left on while the car is in use. But it would ruin the aesthetic value of the car to have bulky buffer panels always attached. Other examples from the prior art offer side door buffer panels which are held in place only by industrial strength magnets. If these magnets were to slip down the car door, the door might be scratched by trapped dirt or irregularities in the magnet face.
SUMMARY
From the foregoing discussion, it should be apparent that a need exists for an apparatus, system, and method that provides protection for the sides of a stationary automobile that is both easy to use and can be quickly put into place. Beneficially, such an apparatus, system, and method would be put in place so quickly that it could become part of the driver's routine. Such an apparatus, system, and method would also be easy to adjust and easy to store when not in use.
The present invention has been developed in response to the present state of the art, and in particular, in response to the problems and needs in the art that have not yet been fully solved by currently available automotive side buffer panels. Accordingly, the present invention has been developed to provide an apparatus, system, and method for automotive side buffer panels that overcome many or all of the above-discussed shortcomings in the art.
This invention protects the sides of an automobile from damaging impacts. Furthermore, this invention is removable and is desired to avoid scratching the automobile. This invention is adjustable so that it can be placed at different heights on the automobile depending on where protection is needed. This invention is also cost-effective, and durable enough to be able to withstand weather and direct sun and cold.
The automobile protection device described in this invention is an inexpensive method of protecting the lateral portions of the automobile while it is stationary. It is made completely of a pliable, resilient, non-abrasive, and light weight material. This material could be polystyrene foam or similar, padded cloth, plain or vulcanized rubber, nylon, or some type of plastic.
In the preferred embodiment, the automobile protection device is made completely of a closed-cell foam. In another embodiment, the closed-cell foam could also be cross-linked for added strength and durability. In one embodiment, the closed-cell foam is a polyethylene. The polyethylene closed-cell foam may also be cross-linked. Both types of polyethylene are simple to manufacture and inexpensive to purchase. Polyethylene foam is rigid enough to protect the side of a car and to absorb multiple impacts, but it is also pliable and soft so as to not damage the car's exterior. This type of material ensures that the automobile protection device will not scratch the automobile body during use.
The design of this automobile protection device makes it very easy to use and to store. It is secured to the automobile by simply closing the automobile door. The automobile protection device is stored by simply folding the apparatus in half or thirds or fourths. In one embodiment, the device is manufactured in the folded position and therefore returns automatically to that position when removed from the automobile body. Under another embodiment, the device is stored by folding the apparatus manually. Unlike other examples from the prior art, the automobile protection device does not, in certain embodiments, require additional attachments to secure it to an automobile surface. Additional attachments increase the complexity and cost of the apparatus and can scratch the automobile surface. The invention may be used on any type or size of automobile. Automobiles can include any size of truck, car, boat, snowmobile, four-wheeler, semi-truck, bus or any other object that has lateral sides that may be impacted.
Reference throughout this specification to features, advantages, or similar language does not imply that all of the features and advantages that may be realized with the present invention should be or are in any single embodiment of the invention. Rather, language referring to the features and advantages is understood to mean that a specific feature, advantage, or characteristic described in connection with an embodiment is included in at least one embodiment of the present invention. Thus, discussion of the features and advantages, and similar language, throughout this specification may, but do not necessarily, refer to the same embodiment.
Furthermore, the described features, advantages, and characteristics of the invention may be combined in any suitable manner in one or more embodiments. One skilled in the relevant art will recognize that the invention may be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments of the invention.
These features and advantages of the present invention will become more fully apparent from the following description and appended claims, or may be learned by the practice of the invention as set forth hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
In order that the advantages of the invention will be readily understood, a more particular description of the invention briefly described above will be rendered by reference to specific embodiments that are illustrated in the appended drawings. Understanding that these drawings depict only typical embodiments of the invention and are not therefore to be considered to be limiting of its scope, the invention will be described and explained with additional specificity and detail through the use of the accompanying drawings, in which:
FIG. 1 a is an orthogonal view of an embodiment of the automobile protection device of the present invention;
FIG. 1 b is an orthogonal view of an embodiment of the automobile protection device of the present invention;
FIG. 2 a is an orthogonal view of an embodiment of the automobile protection device of the present invention;
FIG. 2 b is an orthogonal view of an embodiment of the automobile protection device of the present invention;
FIG. 3 a is an orthogonal view of an embodiment of the automobile protection device of the present invention;
FIG. 3 b is an orthogonal view of an embodiment of the protrusion with annular attachment of the present invention;
FIG. 4 is an orthogonal view of an embodiment of the automobile protection device of the present invention;
FIG. 5 a is an orthogonal view of an embodiment of the automobile protection device of the present invention;
FIG. 5 b is a cross sectional view of an embodiment of the elongated section of the present invention;
FIG. 5 c is a cross sectional side view of and embodiment of the automobile protection device of the present invention;
FIG. 6 is a side view of and embodiment of the automobile protection device of the present invention;
FIGS. 7 a and 7 b are an orthogonal view and a side view, respectively, of an embodiment of the automobile protection device of the present invention;
FIG. 8 is a side view of and embodiment the automobile protection device of the present invention;
FIG. 9 is a perspective view of an embodiment of the automobile protection device of the present invention;
FIG. 10 is a perspective view of an embodiment of the automobile protection device of the present invention;
FIG. 11 is a perspective view of an embodiment of the automobile protection device of the present invention;
FIG. 12 is a perspective view of an embodiment of the automobile protection device of the present invention;
FIG. 13 is a perspective view of an embodiment of the automobile protection device of the present invention;
FIG. 14 is a side view of an embodiment of the automobile protection device of the present invention;
FIG. 15 is a schematic flow chart diagram illustrating one embodiment of the automobile protection device of the present invention;
FIG. 16 is a perspective view of an embodiment of the automobile protection device of the present invention;
FIG. 17 is an orthogonal view of an embodiment of the automobile protection device of the present invention;
FIG. 18 a is a side view of an embodiment of the automobile protection device of the present invention;
FIG. 18 b is a side view of an embodiment of the automobile protection device of the present invention;
FIG. 19 a is a side view of an embodiment of the automobile protection device of the present invention;
FIG. 19 b is a side view of an embodiment of the automobile protection device of the present invention;
DETAILED DESCRIPTION
Reference throughout this specification to “one embodiment,” “an embodiment,” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.
Furthermore, the described features, structures, or characteristics of the invention may be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided to give a thorough understanding of embodiments of the invention. One skilled in the relevant art will recognize, however, that the invention may be practiced without one or more of the specific details, or with other methods, components, materials, and so forth. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of the invention.
Under the embodiment of FIGS. 1 a and 1 b , the automobile protection device 100 consists of a compliant elongated section 102 and a compliant protrusion 104 which may extend perpendicularly from the elongated section 102 . Under one embodiment, both the elongated section 102 and the protrusion 104 are made of closed-cell foam that is selected for impact absorption. The foam, in selected embodiments, is nonabrasive to the surface of the automobile, but has sufficient structural strength to withstand impacts from objects.
Under the embodiment of FIGS. 1 a and 1 b , the elongated section 102 has a semicircular cross section 106 . The flat section 108 of the semicircular cross section 106 is designed to be placed against the automobile body. The semicircular section 110 of the semicircular cross section 106 is designed to ensure that the automobile protection device 100 will stop objects before they impact the body of the automobile. When an object impacts the compliant elongated section 102 of the elongated pad, the foam absorbs the force of the impact before it can damage the body of the automobile.
Under one embodiment, the elongated section 102 has a rectangular cross section. Under another embodiment, the rectangular cross section of the elongated section 102 has rounded edges designed to ensure that the elongated section 102 does not scar the surface of the automobile. Under one embodiment, the elongated section 102 has an oval cross section. Under another embodiment, the elongated section 102 has a circular cross section.
Under one embodiment the elongated section 102 may be up to 8 feet long, 3 inches wide, and 3 inches think. Of course, the dimensions of the elongated section 102 may be selected to accommodate different sizes of automobile. Due to the ease of manufacturing, the elongated section 102 can be made to a plurality of lengths to accommodate different sizes of automobile, and may be customizable by the user.
Under the embodiments of FIGS. 1 a and 1 b , the lateral ends of the elongated section 102 are flat. Under another embodiment, the lateral ends of the elongated section 102 come to a point in a pyramid shape. Under another embodiment, the lateral ends of the elongated section 102 are rounded.
Under one embodiment, the elongated section 102 is made of a closed cell foam material. The elongated section 102 can be inexpensively manufactured in this embodiment because it is manufactured from a single material. Under one embodiment, the elongated section 102 has a soft plastic coating. The coating can be colored or printed on. The soft plastic coating ensures that the elongated section 102 does not scratch the automobile body. In one embodiment, the elongated section 102 is coated in a nylon material. Other materials that the device 100 may be formed of include polystyrene, padded cloth, normal or vulcanized rubber, nylon, plastic, or cross-linked or non cross-linked material.
Under one embodiment, the protrusion 104 extends perpendicularly from the elongated section 102 and is designed to be closed in the automobile door to hold the automobile protection device 100 in the desired location. The protrusion 104 is constructed of a material that can be compressed. Under one embodiment, the protrusion 104 is situated at the midpoint of the elongated section 102 . Under another embodiment, a plurality of protrusions 104 are attached to the elongated section 102 at different locations to secure the automobile protection device 100 at different points on the automobile. Under one embodiment, the elongated section 102 and the protrusion 104 are one integral part and are made of the same material.
Under one embodiment, the protrusion 104 has an oval cross sectional shape. Under another embodiment, the protrusion 104 has a rectangular cross sectional shape. Under one embodiment, the protrusion 104 is 5 inches long, ½ inches thick and 2 inches wide.
Under the embodiment of FIGS. 1 a and 1 b , the protrusion 104 is attached to the elongated section 102 on one end and has a semicircular shape on the other end. Under another embodiment, the protrusion 104 has a squared end opposite the end that is attached to the elongated section 102 .
Under one embodiment, there is a fillet where the protrusion 104 meets the elongated section 102 . This adds strength to the attachment between the elongated section 102 and the protrusion 104 . In one embodiment, the protrusion 104 is the same width as the elongated section 102 and extends perpendicularly from it. In one embodiment, the protrusion 104 is wider than the elongated section 102 to add strength to the protrusion 104 and to ensure that more material is secured to the automobile body. Under one embodiment, the protrusion 104 is completely semicircular in shape and extends from the midpoint of the elongated section 102 .
Under one embodiment, the protrusion 104 is made from a compressible material that does not scratch the body of the automobile. The material is maybe a closed-cell foam material. Under one embodiment, the closed-cell foam is a polyethylene material. Under another embodiment, the closed-cell polyethylene foam may also be cross-linked for added strength. Under one embodiment, the protrusion 104 has a plastic skin material to improve the aesthetic quality of the protrusion 104 and to help ensure that it does not rip when enclosed in an automobile door. Under another embodiment, the protrusion 104 has a closed-cell foam skin designed to ensure that it does not rip when enclosed in an automobile door. Under one embodiment, an outer skin material is made from nylon or spandex and may be used to cover the protrusion 104 .
FIG. 2 a shows an embodiment of the automobile protection device 200 in which the protrusion 204 is inserted into a pre-drilled hole 212 in the elongated section 202 . The long thin portion of the protrusion 204 is designed to be inserted in the pre-drilled hole 212 in the elongated section 202 . The protrusion 204 contains a stopper 214 configured to ensure that the protrusion 204 secures to the elongated section 202 once inserted in the pre-drilled hole 212 . Under one embodiment, the protrusion 204 is held to the elongated section 202 by a raised portion on the long thin portion of the protrusion 204 . The raised portion compresses while the protrusion 204 is pushed through the pre-drilled hole 212 and expands when it is through the pre-drilled hole 212 . In this way, the protrusion 204 cannot easily come out of place from the elongated section 202 .
Under the embodiment of FIG. 2 a , the stopper 214 can be made from the same material as the protrusion 204 or it can be made from a harder, denser and more durable material to ensure that it braces against the elongated section 202 . Under one embodiment, the stopper 214 and the protrusion 204 are made from the same pliable material as the elongated section to ensure that the portion of the automobile protection device 200 contains the pre-drilled hole 212 is still protected.
Under the embodiment of FIG. 2 a , the stopper 214 can be made from the same material as the protrusion 204 or it can be made from a harder, denser and more durable material to ensure that it braces against the elongated section 202 . Under one embodiment, the stopper 214 and the protrusion 204 are made from the same pliable material as the elongated section to ensure that the portion of the automobile protection device 200 containing the pre-drilled hole 212 is protected.
Under this embodiment, the protrusion 204 may be replaced if lost or broken, without the need to replace the elongated section 202 . Also, if the protrusion 204 becomes worm after being closed in an automobile door several times, it can be replaced without replacing the elongated section 202 .
Under the embodiment of FIG. 2 b , the elongated section 202 contains a plurality of pre-drilled holes 212 to accommodate the protrusion 204 . The protrusion 204 may be placed in any of the pre-drilled holes 212 depending on the desired location of the protrusion 204 . This allows the elongated section 202 to be placed in different horizontal position along the automobile. Also, the automobile protection device 200 can be secured to an automobile at a plurality of locations through the use of a plurality of protrusions 204 placed in the plurality of pre-drilled holes 212 .
Under the embodiment of FIGS. 3 a and 3 b , the protrusion 304 consists of an annular shaped piece 316 connected with the protrusion 304 . The annular shaped piece 316 consists of a hole shaped to fit tightly around the elongated section 302 , and an outer section designed to attach to the protrusion 304 at one point. Under one embodiment, the annular shaped piece 316 is the same width as the protrusion 304 . Under one embodiment, the annular shaped piece 316 is designed to give it the needed strength to prevent tearing of the material when the automobile protection device 300 is in use. Under one embodiment, the annular shaped piece 316 is a ½ inch thick. The annular shaped piece 316 is attached to the protrusion 304 through the use of an adhesive. In one embodiment, the annular shaped piece 316 is manufactured as an integral part of the protrusion 304 and is made from the same material as the protrusion 304 . Under one embodiment, the area on which the protrusion 304 attaches to the annular shaped piece 316 has a filleted edge to give added strength to the connection between the protrusion 304 and the annular shaped piece 316 .
The inner portion of the annular shaped piece 316 is shaped to fit tightly around the perimeter of the elongated section 302 . This allows the protrusion 304 to slide along the longitudinal axis of the elongated section 302 . In this way, the protection from the automobile protection device 300 can be situated in the desired position simply by moving the protrusion 304 along the elongated section 302 before closing the automobile door on the protrusion 304 . This also allows the user to remove and replace the annular shaped piece 316 and the protrusion 304 without replacing the entire automobile protection device 300 . These sections will likely need to be replaced before the elongated section 302 , as they are designed to be closed in an automobile door.
Under the embodiment of FIGS. 3 a and 3 b , the protrusion 304 and the annular shaped piece 316 are constructed of a pliant material that can be closed in an automobile door. In one embodiment, the protrusion 304 and the annular shaped piece 316 are made of the same material as the elongated section 302 . In one embodiment, the material is a closed-cell foam. In one embodiment, there is a plastic skin on the annular shaped piece 316 and the protrusion 304 .
Under the embodiment of FIG. 4 , the elongated section 402 contains cavities 418 wherein a second set of elongated pads 420 are placed. The cavities 418 are designed to fit tightly around the perimeter of the second set of pads 420 . The perimeter of the second set of pads 420 and the cross sectional shape of the cavities 418 is similar in shape. The cavities 418 are slightly larger than the perimeter of the second set of pads 420 to ensure that the second set of pads 420 can move within the cavities 418 . The cavities 418 are disposed along the longitudinal axis of the elongated section 402 . The cavities 418 are disposed on the longitudinal ends of the elongated section 402 and extend toward the center of the elongated section 402 . The cavities 418 do not connect to create one long cavity that extends the entire length of the elongated section 402 .
Under one embodiment, the cross sectional shape of the cavities 418 and the cross sectional shape of the second set of pads 420 is rectangular. Under one embodiment, the cross sectional rectangular shape has rounded edges designed to ensure that the second set of pads do not scar the surface of the automobile. Under one embodiment, the cross sectional shape of the cavities 418 and the cross sectional shape of the second set of pads 420 is circular.
Under one embodiment, the cavities 418 are less deep than the total length of the second set of pads 420 . This ensures that an end of the second set of pads 420 protrude from the lateral surfaces of the elongated section 402 .
The second set of pads 420 are designed to be moved horizontally to extend the length of the elongated section 402 . Under one embodiment, the second set of pads 420 contain a ridge on the end toward the interior of the elongated section 402 to ensure that the second set of pads 420 to not entirely leave the cavity 418 of the elongated section 402 .
Under one embodiment, the second set of pads 420 are made of a pliable material similar to that of the elongated section 402 . Under one embodiment, the second set of pads 420 are made of a material that is more stiff than the elongated section 402 to ensure that the second set of pads 420 retain their structural integrity as they extend from the end of the elongated section 402 . Under one embodiment, the second set of pads 420 are covered in plastic coating.
Under the embodiment in FIGS. 5 a , 5 b , and 5 c , a plurality of magnets 522 are imbedded in the elongated section 502 . The magnets 522 are incrementally spaced throughout the elongated section 502 . When the protrusion 504 is closed in the automobile door, the magnets 522 are designed to attract to the metal exterior of the automobile and further ensure that the automobile protection device 500 adheres to the exterior of the automobile body. Under the embodiment of FIG. 5 b , the magnet is completely embedded in the pliable material of the elongated section 502 so that there is always a layer of foam 524 between the automobile body and the magnet surface. This ensures that the magnets 522 do not damage the surface of the automobile.
Under one embodiment, the magnets 522 have at least one flat side that is designed to face the automobile surface. Under one embodiment, the magnets 522 are rectangular. Under another embodiment, the magnets 522 are cylindrical in shape. Under one embodiment, the magnets 522 are flexible magnets. Under another embodiment, the magnets 522 are plastic coated to ensure that they do not scar the surface of the automobile. Under one embodiment, the magnets 522 are designed to be of a size and strength that will attract to the surface of the automobile and then be easily removed.
Under one embodiment, the magnets 522 are placed in the elongated section 502 during the manufacturing process. Under one embodiment, the magnets 522 are manufactured as an integral part of the elongated section 502 . Under another embodiment, the magnets 522 are placed in the elongated section 502 . Under another embodiment, the magnets 522 are placed in the elongated section 502 after the elongated section 502 has been manufactured. Under this embodiment, the magnets 522 can be removed by the user.
Under one embodiment, two magnets 522 are embedded in the elongated section 502 on the longitudinal ends of the elongated section 502 . Under another embodiment, the magnets 522 are designed to help secure the automobile protection device 500 to the exterior of the automobile and to assist in storing the device by holding the elongated section 502 in the folded position when it is stored. When the elongated section 522 is folded for storage, the magnets 522 attract to each other and secure the elongated section 522 in the folded position.
Referring now to FIG. 6 , in one embodiment, the automobile protection device 600 is folded at a plurality of locations in order to store the automobile protection device 600 . Under one embodiment, the automobile protection device 600 is folded in half. Under another embodiment, the automobile protection device 600 is folded in thirds. Under one embodiment, the automobile protection device 600 is folded in fourths. The automobile protection device can be folded in a plurality of manners for storage. The device 600 maybe seamed or scored.
Under the embodiment of FIG. 6 , the automobile protection device 600 is folded in half for storage. The closed-cell foam material allows the elongated section 602 to fold back onto itself to save space during storage. Under one embodiment, the protrusion is on the interior of the fold of the elongated section 602 .
Under the embodiment of FIGS. 7 a and 7 b , the elongated section 702 contains a slit 726 in the center of the elongated section 702 . The slit 726 is disposed through the rounded section of the cross section of the elongated section 702 . In this way, sections of the elongated section 702 remain connected by the material that is not cut by the slit 726 . The slit 726 allows the elongated section 702 to fold completely back on itself for storage. When the automobile protection device 700 is in use, the slit 726 does not affect its performance because the sections of the elongated section 702 separated by the slit 726 contact each other and cover the slit 726 area. In one embodiment, the slit 726 is disposed on the opposite side of the elongated section 702 from the protrusion 704 .
Under the embodiment of FIG. 8 , the elongated section 802 is held in the folded position through the use of straps 828 . Under another embodiment, the straps 828 are provided by the user. The straps 828 can include rope, string, flexible, resilient cords, tape or other securing devices.
FIG. 9 shows the automobile protection device 900 positioned in the door jamb area 932 . In one embodiment, the protrusion 904 is designed to be closed in the door jamb area 932 of an automobile. The automobile can be any type of car, truck, snowmobile, bus or other object that has lateral sides that need to be protected from contact with other objects.
Under the embodiment of FIG. 10 , the protrusion 1004 is designed to be caught in the door jamb area 1032 . The protrusion 1004 is designed to hold the automobile protection device 1000 to the surface of the automobile. In one embodiment, the protrusion 1004 is designed to easily close in any part of the automobile door or window.
Under the embodiment of FIG. 11 , the elongated section 1102 is designed to unfold and rest against the body of the automobile. The positioning of the automobile protection device 1100 is adjustable depending on where the protrusion (not shown in this figure) is closed in the automobile door. The automobile wheels, wheels rims, body and door can all be covered by the automobile protection device 1100 .
Under the embodiment of FIG. 12 , a second set of pads 1220 are extended from the elongated section 1202 . Under one embodiment, the second set of pads 1220 are half the length of the elongated section 1202 .
Under the embodiment of FIG. 13 , the automobile protection device 1300 is designed to be easily removable from the automobile door 1330 .
Under the embodiment of FIG. 14 , the automobile protection device is configured to be folded for easy storage. The elongated section 1402 is folded in half. Because the automobile protection device is removable and does not require any modification to the automobile, it is reusable on any style or size of automobile.
The schematic flow chart diagram that follows is generally set forth as a logical flow chart diagram. As such, the depicted order and labeled steps are indicative of one embodiment of the presented method. Other steps and methods may be conceived that are equivalent in function, logic, or effect to one or more steps, or portions thereof, of the illustrated method. Additionally, the format and symbols employed are provided to explain the logical steps of the method and are understood not to limit the scope of the method. Although various arrow types and line types may be employed in the flow chart diagrams, they are understood not to limit the scope of the corresponding method. Indeed, some arrows or other connectors may be used to indicate only the logical flow of the method. For instance, an arrow may indicate a waiting or monitoring period of unspecified duration between enumerated steps of the depicted method. Additionally, the order in which a particular method occurs may or may not strictly adhere to the order of the corresponding steps shown.
FIG. 15 is a schematic flow chart diagram illustrating one embodiment of a method 1500 protecting lateral surfaces of automobiles. In one embodiment, the method 1500 starts 1502 and the user opens 1504 the automobile door 930 , of FIG. 9 , and places 1506 the protrusion 904 in the door jamb area 932 . FIG. 9 shows that the protrusion 904 is positioned so that it will be caught in the door 930 when the door 930 is closed. The automobile door 930 is then closed 1508 on the protrusion 904 . FIG. 10 shows and embodiment of the automobile protection device 1000 with the protrusion 1004 caught in the door jamb area 1032 . The protrusion 1004 holds 1510 the automobile protection device 1000 to the surface of the automobile. The protrusion 404 1004 can be closed in the automobile door at different vertical positions to protect different portions of the automobile. In certain situations, the user may expect contacts at a certain vertical level and will place the automobile protection device 1000 at that level.
Once the automobile door 1130 of FIG. 11 is closed, the elongated section 1102 unfolds 1512 and rests against the body of the automobile. FIG. 11 also shows that the automobile protection device 1100 can be positioned to cover more than just the automobile door 1130 . The elongated section 1102 rests horizontally on the automobile body and extends outward from the surface of the automobile body to absorb blows from surrounding objects, especially adjacent automobile doors. FIG. 12 shows an embodiment containing a second set of pads 1220 . Once the elongated section 1202 unfolds and rests against the body of the automobile, the second set of pads 1220 can be extended to protect more of the automobile surface. Referring now to FIG. 13 , to remove the automobile protection device 1300 , the automobile door 1330 is opened 1514 and the protrusion 1304 is removed 1516 from the door jamb area 1332 . The automobile protection device is folded 1518 for storage by folding the elongated section 1402 in half as shown in FIG. 14 . Because the automobile protection device is removable and does not require any modification to the automobile, it is reusable on any style or size of automobile. The method 1500 then ends 1520 .
Under the embodiment of FIG. 16 , the protection system 1600 is designed to be caught in the door jamb area of the car. In this configuration, the entire side of the car is protected from side impacts from neighboring cars.
Under the embodiment of FIG. 17 , the automobile protection device 1700 is manufactured in the folded position. This ensures that the natural resting position of the automobile protection device 1700 is in the folded position and creates a spring back force to return the automobile protection device 1700 to this position when removed from the surface of the automobile. The spring back force created by manufacturing the automobile protection device 1700 in the folded position also presses the elongated section 1702 against the body of the automobile when the automobile protection device 1700 is in use. Under this embodiment, the automobile protection device 1700 returns to a folded position automatically and can then be easily stored without the use of any type of fastener. The spring back force holds the folded portions of the elongated section 1702 in the folded position during storage.
Under the embodiment of FIGS. 18 a and 18 b , the automobile protection device 1800 is shown with a stretchy, elastic band 1804 that can be utilized to keep the protection device 1800 in a folded position for storage. FIG. 18 a shows how the protection device 1800 can be folded in half, with the protrusion 1802 held between the outer arms of the device, by an elastic band 1804 that is pulled down so as to keep the device 1800 in its folded position. FIG. 18 a shows how the elastic band 1804 can be pulled back so as to allow the protection device 1800 to open up and become functional. The stretchy, elastic band has a seam 1806 stitched in place so that the band stays on the device 1800 even when the device is being used on a parked car.
Another storage technique is shown in FIGS. 19 a and 19 b . In FIG. 19 a , the protection device 1900 is open and ready for use. A stretchy, spandex type material is sewn into a sleeve 1904 which is put in place on the device 1900 and placed about the protrusion 1902 so that the protrusion is still able to be shut into the car door. Attached to the sleeve 1904 at one end is an elastic band 1906 which is left slack when the protection device 1900 is deployed. FIG. 19 b shows how the elastic band 1906 is stretched around the protection device 1900 when it is folded in half for storage. The spandex-like sleeve 1904 keeps the elastic band 1906 from slipping off the end of the device 1900 . In this configuration, folding the protection device 1900 for storage is very easy and quick.
The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.
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An apparatus and a system are disclosed for protecting the side doors of an automobile when it is parked. The apparatus includes an elongated pad having two opposing ends and a central portion disposed between the two endings, and a protrusion extending from the central portion of the elongated pad and formed of a material sufficiently compressible to be shut within the door of an automobile. The system includes an elongated pad having two opposing ends and a central portion disposed between the two endings, and an adjustable protrusion extending from the central portion of the elongated pad, the adjustable protrusion movable to different locations along the length of the elongated pad, the protrusion is formed of a material sufficiently compressible to be shut within the door of an automobile.
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BACKGROUND OF THE INVENTION
Field of the Invention and Description of Related Art
[0001] U.S. patent application Ser. No. 11/410,022 of the present applicant relates to a process for obtaining cefotetan of formula
substantially free of the disodium salt tautomer of formula
[0002] This process makes it possible to obtain a substantially pure cefotetan acid, but has the drawback of being rather lenghty and poorly productive: in other words, it is not particularly suitable for industrial application with the production of large batches.
SUMMARY OF THE INVENTION
[0003] The present applicant has therefore sought to devise a simple process which is easy to use and is highly productive. As a result of these efforts, the present inventors have surprisingly found that cefotetan can be recrystallized in pure form, substantially free of tautomer (less than 0.2%), by an easily applied process.
[0004] This process is based on the capacity of the cefotetan tautomer to bind to Al 3+ ions which can be provided in the form of aluminium chloride or as neutral alumina, or even to ions such as Fe 3+ or Cr 3+ (probably by forming stable complexes with the oxygen atoms present on the isothiazole part of the molecule of the tautomer of formula (II) at around pH 7.0, to form a precipitate which is eliminated by filtration, while the cefotetan remains in aqueous solution as alkaline carboxylate.
[0005] A further advantage of the present method is the ease of recovery of the neutral alumina used in the process, so that it can be recycled with considerable cost saving.
[0006] The process of the invention enables cefotetan of formula (I) to be obtained containing up to 0.2% of the tautomer of formula (II) in its acid form and with a K.F. up to 2.5%, concentration on dry basis at least 99.0% and free of solvents, both in the acid form and in the sodium salt obtained from it.
[0007] This process is characterised in that an aqueous solution of crude cefotetan cooled to between 0° and +4° C. is brought into contact with Al 3+ ions originating from a reagent chosen from neutral alumina, anhydrous aluminium trichloride and aluminium trichloride hexahydrate, or with Fe 3+ or Cr 3+ ions, to cause formation of a precipitate with the aforesaid tautomer compound, at pH within the range 7.0-7.2, this precipitate being eliminated by filtration to provide a solution containing cefotetan substantially free of tautomer, from which the cefotetan is precipitated by acidification to pH within the range 1.3-1.5 and isolated by filtration between 0° and +4° C. to provide a substantially tautomer-free cefotetan with a K.F. up to 2.5%, concentration on dry basis at least 99.0% and free of solvents.
DETAILED DESCRIPTION OF THE INVENTION
[0008] The implementation of the process will be more apparent from the ensuing detailed description of a practical embodiment thereof, given by way of non-limiting example.
EXAMPLE 1
Use of Neutral Alumina
[0009] 300 g of wet crude cefotetan originating from synthesis and equivalent to about 80 g of pure cefotetan are suspended in 800 ml of osmotized water. The suspension is cooled to between 0° and +4° C., and 35 g of sodium bicarbonate are added in portions, without exceeding pH 6.8.
[0010] The pH is corrected to 7.0-7.2 with a solution of 8 g sodium bicarbonate in 100 ml of osmotized water. 120 g of neutral alumina are added, and the pH maintained at 7.1-7.2 between 0° and +4° C. by adding carbon dioxide or an 8% sodium bicarbonate solution. The mixture is agitated for 60 min, the pH is corrected to 6.4 with carbon dioxide, and the alumina is filtered off and washed three times with 100 ml osmotized water.
[0011] The pH is corrected to 5.3-5.5 with 5% HCl again at between 0° and +4° C. Agitation is again applied and the cefotetan initially precipitated returns into solution, 1.5 g of decolorizing carbon are added and the mixture agitated at between 0° and +4° C. for 20 min. It is again filtered and the filter washed 3 times with 100 ml of osmotized water.
[0012] The pH of the rich aqueous solution is lowered to 1.3-1.5 by adding 15% HCl at between 0° and +40° C. over about 60 min. The mixture is agitated at between 0° and +4° C. for 40 min, and then filtered under vacuum, washing the filter 3 times with 100 ml of osmotized water, acidified with HCl to a content of about 0.1% and cooled to between 0° and +4° C., then washing twice with 100 ml osmotized water alone, precooled to between 0° and +4° C. About 200 g of wet cefotetan are obtained, which is dried under vacuum at 24°-27° C. under a light stream of nitrogen.
[0013] Yield: 65-70 g of pure cefotetan, K.F. ≦2.5%, concentration on dry basis ≧99.0%, tautomer ≦0.2%, solvent free.
EXAMPLE 2
Use of Anhydrous Aluminium Trichloride
[0014] 60.72 g of wet crude cefotetan, at a concentration of 24,7% and containing between 2.5% and 3.0% of tautomer, are fed into 270 ml of demineralized water between 0° and +5° C. After 20 min of agitation, 12.0 g of potassium bicarbonate are added in 15 minutes still at 0° and +5° C. The mixture is stirred for half hour at 0° and +5° C., complete solubilization is obtained and the pH is stabilized at 7.0.
[0015] The solution is kept under vacuum at between 0° and +5° C. to remove the dissolved carbon dioxide, the pH rising to 7.3-7.4. Draw-off of carbon dioxide under vacuum is continued while maintaining the pH between 7.3 and 7.4 by adding 1N HCl. After about 30 min the solution appears perfectly clear. At this point 2.0 g of anhydrous AlCl 3 are added in small portions of about 0.16 g each, over about half hour while maintaining the temperature between 0° and +5° C. and the pH between 7.3 and 6.6. The additions of anhydrous AlCl 3 and aspiration to remove the carbon dioxide are alternated in order to maintain the pH within the range of 6.6 to 7.3. On termination of the anhydrous AlCl 3 addition the mixture is maintained under agitation and reduced pressure for 45-50 minutes at between 0° and +5° C., the pH being maintained at 6.9-7.1 by small additions of 1N HCl. The pressure is returned to atmospheric, the pH is fixed at 6.9 and the solution filtered between 0° and +5° C. through a porous septum covered with the following layers starting from the bottom: fabric, cotton, celite filter. The reaction solution, maintained between 0° and +5° C., is filtered under minimum vacuum, checking that the pH remains constant between 6.9 and 7.1. The filtered solution is cloudy and is re-filtered through the same filter a further three times without however obtaining a perfectly clear solution. The filter is finally washed with 4×80 ml portions of cold demineralized water. The pH is corrected to 4.5-4.7 with 15% HCl at between 0° and +5° C. 1.5 g of decolorizing carbon and 0.15 g of EDTA are added. The mixture is filtered and the filter washed with 4×40 ml portions of cold demineralized water. 300 ml of methylethylketone are added followed by 50 g of NaCl. The mixture is agitated for 15 min to completely dissolve the salt, then the pH is lowered to 1.5 with 15% HCl at between 0° and +5° C. The phases are separated after at least 20 min at between 0° and +5° C., then 150 ml of methylethylketone and 50 g of sodium chloride are added to the aqueous phase. When the salt has dissolved, the pH is checked to be ≦1.5, the temperature is raised to 20° C. and the phases allowed to separate for at least 30 min. The two organic phases are pooled, decolorized with 1.5 g of carbon for 15 min, filtered and the filter washed 3 times with 25 ml methylethylketone. The decolorized organic solution is concentrated to 260-280 ml by distilling off the methylethylketone under reduced pressure at 30°-31° C. 320 ml demineralized water are added, the mixture cooled to between 0° and +5° C. and 4.4 g of potassium bicarbonate added under agitation while maintaining the pH between 6.0 and 6.5, and in any event ≦6.5. The phases are separated and the organic phase discarded, while the aqueous phase is corrected to pH 4.5-4.7 with 5% HCl. The aqueous phase is decolorized with 1.0 g carbon at between 0° and +5° C. and maintained under reduced pressure for 20 min. The mixture is filtered, the filter washed twice with 40 ml demineralized water, the system returned to atmospheric pressure and the pH corrected to 3.6-3.7 with 5% HCl at between 0° and +5° C. The temperature is raised to 20° C., the methylethylketone which has remained dissolved is distilled off under reduced pressure, a crystal of pure cefotetan is added and the mixture left to crystallize for 45 min at pH 3.6-3.7, while maintaining reduced pressure to remove further methylethylketone which may be present. Atmospheric pressure is restored and 5% HCl dripped in over 15 min until pH 3.0.
[0016] Reduced pressure is again applied and the mixture heated to 30° C., the pH then being lowered to 2.5 with 5% HCl over 15 min. The operation is repeated to reduce the pH firstly to 2.0 and then to 1.5 with 5% HCl, each time returning to reduced pressure at 30° C., until pH 1.5 remains constant for 30 min. The mixture is cooled to between 0° and +5° C. and agitated for 60 min under reduced pressure. Atmospheric pressure is restored, the mixture filtered, the filter washed with 61 ml of 1% HCl at between 0° and +5° C., then with 61 ml of demineralized water at the same temperature.
[0017] On drying, 11.0 g of cefotetan are obtained with a concentration on dry basis ≧99.0% and with tautomer ≦0.2%, K.F. <2.5%.
[0018] The same results are obtained on using aluminium trichloride hexahydrate in a quantity equivalent to the anhydrous aluminium trichloride of the aforedescribed example.
EXAMPLE 3
Recovery of Spent Alumina
[0019] To recover the spent neutral alumina the wet neutral alumina originating from 240 kg of virgin neutral alumina is loaded into a comber filter. A solution of 40 kg of 30% soda in 1000 l of demineralized water is eluted at ≦20° C. Nitrogen is blown into the filter for drying purposes and elution is repeated with a further 40 kg of 30% sodium hydroxide in 1000 l demineralized water. When the last fraction is colourless, elution is carried out with at least 10000 l of demineralized water to a pH between 8 and 9.
[0020] The regenerated alumina is suspended in 1000 l of demineralized water at a temperature of ≦20° C. Agitation is applied and the pH corrected to 6.7-7.3 with 5% HCl until constant pH within this range. The mixture is filtered, and washed with at least 1000 l of demineralized water in portions, until the last wash presents a conductivity <500 microSiemens (μS).
[0021] 310-320 kg of wet product are recovered, corresponding to 220-230 kg of dry neutral alumina.
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The invention relates to a method for obtaining cefotetan acid substantially free of tautomer, by treating crude cefotetan with Al 3+ ions which cause the tautomer to precipitate. The precipitate is eliminated by filtration to provide a solution from which practically tautomer-free cefotetan is obtained.
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BACKGROUND OF THE INVENTION
The present invention relates to power tools for attaching connectors to electrical power distribution lines.
U.S. Pat. No. 4,722,189 assigned to Burndy Corporation is directed to an explosively operated tool for connecting a tap or branch cable to a permanently installed main power cable. The connection between main cable and tap cable is established by means of a C-shaped sleeve joining the spaced tap and main cables and by a wedge driven into the space between the cables within the C-shaped connector sleeve. Strong physical and electrical connections are established by the connector.
The tool disclosed in the '189 patent drives the wedge into the C-shaped sleeve in the space between the main cable and the tap cable as the cable connection is established. The power tool includes an anvil and power ram which engage the connector workpiece and drive the connector wedge into final position. The power tool uses an explosive charge which generates sufficient force to drive the wedge into the sleeve between main cable and tap wire. As disclosed in U.S. Pat. No. 4,722,189, the power tool and cartridge case have interrelted designs and modes of operation for safe operation.
The explosive charge includes a tubular cartridge case, a rim-fire power cell held by a supporting collar, and a power piston for transmitting explosive force to the power ram when operating the power tool. The tubular cartridge is open-ended and the collar positions the rim-fire power cell at the breech end of the cartridge. The power piston is fitted in the cartridge case ahead of the power cell for engagement with the power ram. The subassembly of power piston and power cell with supporting collar are slidably mounted within the cartridge case so that the power cell can be spaced inwardly from the breech end of the cartridge case. In the assembled cartridge case, the power cell is recessed within the case and is inaccessible to a firing pin in order to avoid premature or inadvertent firing until the power tool is armed and manipulated for safe firing by the operator. The cartridge case is loaded into the tool with a safely recessed power cell inaccessible to the firing pin. After inserting the cartridge case into a firing chamber, the tool is further manipulated so that the power ram enters the open muzzle end of the cartridge case, pushes the power piston and power cell to the breech end of the cartridge case bringing the rim-fire power cell within range of the firing pin in ready-to-fire condition. The ready-to-fire condition of the cartridge case occurs as the operator manipulates the power tool and places the anvil and power ram into engagement with a connector workpiece positioned between main and tap cables. As a result of the interrelated design of cartridge case and power tool, the power tool cannot be fired until the operator engages a connector workpiece in the course of establishing the cable interconnection. The tool then is ready to be fired.
If, for some reason, the operator decides not to fire the power cartridge and disengages the power tool from an unfinished workpiece connector, then the cartridge case will remain in the ready-to-fire position and present a hazardous condition if the tool is not immediately used or if the cartridge case is not immediately extracted from the firing chamber. The present invention, therefore, is directed to a safety arrangement by which an explosively operated tool with cartridge case in the ready-to-fire position can be disarmed and returned to a safe (not ready-to-fire) position in the event the operator decides not to fire the tool after arming it and disengages the tool from an unfinished connector workpiece.
SUMMARY OF THE INVENTION
The present invention is directed to an improvement in Explosively Actuated Tools of the kind disclosed in U.S. Pat. No. 4,722,189. The present invention utilizes a power booster cartridge as disclosed in the '189 patent in which an open-ended cartridge includes a power transmitting piston and a collar mounted power cell slidably assembled within the cartridge case. The power cell contains a powder charge sufficient to operate the tool. The power piston is positioned ahead of the power cell in the cartridge case and engages the rear end of the power ram extending into the cartridge case through its open muzzle end. When the cartridge case is fired, the explosive force of the power cell drives the power piston and power ram out of the cartridge case driving the connector wedge into place. In the not ready-to-fire condition, the power cell, particularly the rim-fire end of the power cell, is recessed inwardly of the open breech end of the cartridge case beyond contact reach of the firing pin within the power tool.
In accordance with this invention, the power tool includes a main breech assembly including a firing chamber for receiving a cartridge case. The breech end of the firing chamber is fitted with a breech plug for engaging the breech end of the cartridge case. The breech plug includes a firing pin and hammer for detonating the power cell when the power tool is in position over a connector workpiece and the tool operator wishes to finish the electrical connection.
The breech plug also is fitted with a breech pad extending into the breech chamber under the force of a compression spring. The breech pad projects from the breech plug face so that it engages the rim-fire end of the power cell when the cartridge case and tool are in ready-to-fire position. In the ready-to-fire position, the power ram of the tool extends into the open muzzle end of the cartridge case, engages the front face of the power piston, and presses the power cell in ready-to-fire confronting relation with the firing pin. The tool is now ready to fire. For its part, the spring loaded breech pad is also in engagement with the power cell having been pushed back from its normal position projecting into the breech chamber so as not to interfere with firing of the power cell.
Should the tool operator decide not to fire and disengage the tool from an unfinished connector workpiece, then by doing so the tool is disarmed. Disarming occurs as the power ram is withdrawn from engagement with the power piston thereby allowing the breech pad under the force of its compression spring to push the rim-fire power cell a short distance into the cartridge case beyond reach of the firing pin. Additionally, the breech pad maintains its position projecting into the cartridge case and keeps the rim-fire power cell away from the firing pin. In this way power tool cannot be fired unless it is engaging an unfinished connector workpiece and the breech pad is pushed back. So, the operator need not extract the cartridge case after disengaging an unfinished connector because the breech pad disarms the cartridge case and the tool cannot be fired prematurely, inadvertently or deliberately as by rapping the firing hammer.
OBJECTS OF THE INVENTION
It is a primary object of the present invention to provide a power actuated tool for installing electrical connector workpieces in which the tool disarms itself when an operator disengages the tool from a connector workpiece without firing the tool.
A further object of the invention is to provide an explosively powered tool which is armed only when it is in engagement with an unfinished connector workpiece.
A further object is to provide a power actuated connector tool which cannot be fired prematurely, inadvertently, or deliberately when the tool is not in engagement with a connector workpiece.
Other and further objects of the present invention will occur to one skilled in the art on employment of the invention in practice or upon an understanding of the following detailed description of the invention.
DETAILED DESCRIPTION OF THE DRAWING
FIG. 1 is a perspective view showing the tool of the present invention in use for installing an electrical connector.
FIG. 2 is a perspective view of an explosively operated tool according to the present invention.
FIG. 3 is a side elevational view partly in section of the main breech action assembly of the power tool according to the present invention.
FIG. 4 is a side elevational view partly in section of the breech plug and breech housing assembly.
FIG. 5 is a side elevational view of the breech plug of the present invention.
FIG. 6 is an exploded view of a cartridge case used with the power tool of the present invention.
FIGS. 7, 8 and 9 are schematic sequential views of the tool of the present invention showing the tool being armed with the cartridge case moved to a read-to-fire position and with the cartridge case thereafter moved to a not ready-to-fire position.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawing, and in particular FIGS. 1 and 2, an explosively operated tool 10 according to the present invention is used for connecting a branch or tap wire 12 to a main power line 14 by means of a connector 15 which establishes a robust physical connection and an efficient electrical connection between the two cables. The connector consists of two pieces including a C-shaped sleeve 16 which couples the wires and a wedge 18 inserted between the wires in the space within the coupling. The tool shown in FIG. 1 is the explosively operated tool described in U.S. Pat. No. 4,722,189 with the improvement of the present invention being held by an operator and illustrating a hammer blow for operating the tool. As shown in FIG. 2, the power tool includes an anvil 20 and ram 22 which engage the connector workpiece in position coupling the two cables with the ram explosively powered to drive the wedge into final position. The tool further includes a base member 24 for mounting the anvil and for receiving a main breech action 26 assembly fitted through a support sleeve 28 at the other end of the base positioning the power ram along the longitudinal axis of the tool in general alignment with the anvil. The main breech action assembly 30 shown also in FIG. 3 includes a main breech member 32 inserted into the support sleeve 28 for adjustment with respect to the anvil by means of a threaded connection 34 and for advancing the power ram and the anvil into engagement with a connector workpiece during the process of establishing a power line connection. The main breech member is threaded at 35 along its forward surface 36 and includes a longitudinal axial bore 37 for receiving the power arm 22 through its muzzle end 38 and defining a firing chamber 40 for receiving a power booster cartridge 42 (FIG. 6) at its breech end 44. The main breech member terminates in a cylindrical housing 39 of greater diameter than the forward surface which accommodates the firing chamber lying along the longitudinal axis x-y of the tool. The firing chamber housing is generally cylindrical and includes on its outer surface a slot 41 having longitudinally 43 and circumferentially 45 extending segments for receiving and guiding a breech housing assembly 47.
The power ram 22 extends into the longitudinal bore 37 and into the firing chamber 40 for transmitting the booster force to a connector workpiece. The ram has greater and lesser diameters with the lesser diameter forward portion 46 being slidably supported by an end bearing 48 securely threaded into the muzzle end 38 of the bore. A crusher sleeve 50 and stop ring 52 are fitted onto the ram adjacent its interdiameter shoulder 54 for engagement with the confronting rear face 56 of end bearing when the power ram is driven forward by the booster cartridge. The breech end of the main breech member includes a captive extractor 58 for extracting each spent cartridge case from the firing chamber.
The breech housing and breech plug assembly 47 is slidably fitted over the firing chamber housing for loading, firing, and extracting booster cartridge cases in the firing chamber and for disarming the tool whenever it is removed from an unfinished workpiece without the power cell being detonated. The front face 60 includes an integral key 62 engaging slot 41 for guiding the breech housing 47 through longitudinal and circumferential movements on the firing chamber housing.
The breech housing is generally cylindrical with a knurled outer surface 64, and a window or breech opening 66 for inserting cartridges into the firing chamber 40. The breech housing also includes a longitudinally extending slot 68 for receiving a safety latch 70 on pivot pin 72 which cooperates with a hammer block 74 to prevent movement of a hammer 76 until the cartridge case is in the firing chamber, the breech housing closed, and the breech housing rotated to remove the hammer block as detailed below. A compression spring 78 tends to rotate the safety latch clockwise as shown in FIG. 3.
The breech plug 80 encloses the breech end 44 of firing chamber 40 and is fitted with hammer mechanism 76, firing pin 82, and safety breech pad 84. The breech plug is secured into the rear end of breech housing by suitable means such as a threaded connection 86. When in place the breech plug shoulder abuts the end face of the firing chamber housing forming a gas tight seal 88. The front face of breech plug is recessed 90 to receive the flanged breech end 92 of a cartridge case 42 with rim-fire power cell 94 in range of firing pin and with the cartridge case held firmly in the firing chamber. Additionally, the breech pad 84 protrudes from breech plug face into the recess 89 engaging the cartridge case 42.
The hammer mechanism 76 occupies a rearwardly open cavity 96 in the breech plug 80 and comprises a generally cylindrical body 98 having a circumferentially extending recess 100 of prescribed width which defines the axial distance travelled by the hammer and firing pin when the hammer actuates the firing pin. A retaining pin 102 carried in a lateral bore 104 in the breech plug extends laterally through the hammer recess and limits the axial distance of travel of the hammer while securing the hammer in the breech plug. The recess 100 is also engaged by the hammer block 74 to prevent hammer movement until the tool is properly armed and ready to fire.
The firing pin 82 is carried by the hammer in a frontward opening cavity 106 and is securely retained therein by a retaining pin 108 occupying a groove 110 in firing pin surface 112. The firing pin tip 114 protrudes through an opening 116 in breech face into the firing chamber for firing a cartridge.
As shown in FIG. 5, the firing pin extends through opening 116 in breech face just above the horizontal axial plane a-b of the breech plug so that the pin has access to rear face 118 of power cell 94 through the open breech end 120 of the cartridge case. In a preferred arrangement of hammer and firing pin, the pin will protrude approximately 0.015 to 0.020 inches into the firing chamber when detonating a cartridge.
The breech pad 84 is received in a longitudinally extending opening 122 in the breech plug just below the horizontal axial plane a-b of the breech plug so that the pad has access to the power cell 94 through the open breech end 120 of the cartridge case. The breech pad comprises a cylindrical main body 124, a forward disc shaped pad 126 with flat front face 128 and a rearward spring retaining finger 130. The main body is recessed at 132 to accommodate a breech pad pin 134 for retaining the breech pad within prescribed limits of longitudinal movement. In the fully extended position the breech pad will extend a distance greater than the excursionary range of the firing pin, i.e., a distance greater than the 0.015-0.020 inch protrusion of the firing pin in a preferred arrangement.
The spring retaining finger 130 extends into a spring cavity 136 of the hammer for receiving a compression spring 138. The compression spring tends to push the breech pad into the firing chamber up to the prescribed limit of travel. By means of reaction force the spring will also urge the hammer and firing pin away from the firing chamber to the limit of its axial distance of travel.
The cartridge case is shown in FIG. 6 and includes open ended shell casing 140, a power cell 94, a supporting collar 142 for the power cell, and a power piston 144 for engaging and driving the power ram when the cartridge is detonated. The shell casing 140 is an elongated tube 146 with open muzzle end 148, a flanged breech end 150 and with an opening 152 in its breech face 154 exposing the power cell 94. The power piston and the power cell collar slide into the shell casing and when assembled to the exposed firing face of the power cell is located safely inside the shell casing out of reach of the tool's firing pin.
FIGS. 7, 8 and 9 illustrate in sequence the safety features of the invention during operation and are used for general reference in summarizing operation of the tool.
Referring first to FIGS. 2 and 3, the tool is loaded by first moving breech housing to its rearmost position on main breech assembly and inserting a safe cartridge (power cell recessed) through breech housing window and extractor opening into the firing chamber. Next the breech housing is pushed forward and rotated on the firing chamber housing approximately one-quarter with key riding in the longitudinal and circumferential portions of housing slot. The longitudinal component of this movement closes breech plug against the firing chamber with the cartridge flange residing in the breech plug recess and with the breech pad confronting the recessed power cell as shown in FIG. 7. Additionally this movement engages the hammer block as the safety latch tip engages the extractor body moving the hammer block counter clockwise into position. The circumferential component of breech housing movement disengages hammer block from the hammer groove so the firing pin can be advanced as the safety latch tip falls into a slot (not shown) in firing chamber housing and the hammer block and safety latch move clockwise.
Now the operator is ready to engage a connector workpiece and advances the power ram by forward rotation of main breech assembly through its support sleeve. When the ram tip engages the connector wedge, relative movement occurs between ram and main breech assembly so the ram breech end enters the cartridge case engaging the front face of power piston and pushing it and the power cell rearwardly from the position of FIG. 7 to that of FIG. 8. Here the breech pad is pushed out of the way and the firing pin is in range of the power cell. The tool is ready to fire and is detonated by a hammer blow of FIG. 1.
If the operator decides not to fire the tool after it reaches the position of FIG. 8 and disengages the tool from the unfinished workpiece by reverse rotation of the main breech member, then the pushing force of ram breech end against power piston is released and the breech pad advances against the power cell and pushes it into the interior of the cartridge case out of range of the operational execursion of the firing pin to the position shown in FIG. 9. The tool is disarmed and now cannot be fired.
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A power actuated tool having an explosive cartridge for applying connectors to power lines wherein the tool is armed as the power tool is loaded with a cartridge and engaged with a connector, and disarmed if the tool operator disengages the connector leaving the connection unfinished.
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CROSS-REFERENCE TO RELATED APPLICATION
This Application a Continuation of U.S. application Ser. No. 11/643,844 filed on Dec. 22, 2006 which is a Continuation of U.S. application Ser. No. 11/082,988 filed on Mar. 18, 2005, now issued U.S. Pat. No. 7,175,256, which is a Continuation of U.S. application Ser. No. 10/893,385, filed on Jul. 19, 2004, now issued U.S. Pat. No. 6,905,194, which is a Continuation of U.S. application Ser. No. 10/291,706, filed on Nov. 12, 2002, now issued U.S. Pat. No. 7,125,106, which is a Continuation of U.S. application Ser. No. 09/609,140, filed on Jun. 30, 2000, now issued U.S. Pat. No. 6,755,513, all of which are herein incorporated by reference.
FIELD OF THE INVENTION
This invention relates to the field of ink jet printing systems, and more specifically to a printhead support assembly and ink supply arrangement for a printhead assembly and such printhead assemblies for ink jet printing systems.
DESCRIPTION OF THE PRIOR ART
Micro-electromechanical systems (“MEMS”), fabricated using standard VLSI semi-conductor chip fabrication techniques, are becoming increasingly popular as new applications are developed. Such devices are becoming widely used for sensing (for example accelerometers for automotive airbags), inkjet printing, micro-fluidics, and other applications. The use of semi-conductor fabrication techniques allows MEMS to be interfaced very readily with microelectronics. A broad survey of the field and of prior art in relation thereto is provided in an article entitled “The Broad Sweep of Integrated Micro-Systems”, by S. Tom Picraux and Paul McWhorter, in IEEE Spectrum, December 1998, pp 24-33.
In PCT Application No. PCT/AU98/00550, the entire contents of which is incorporated herein by reference, an inkjet printing device has been described which utilizes MEMS processing techniques in the construction of a thermal-bend-actuator-type device for the ejection of a fluid, such as an ink, from a nozzle chamber. Such ink ejector devices will be referred to hereinafter as MEMJETs. The technology described in the reference is intended as an alternative to existing technologies for inkjet printing, such as Thermal Ink Jet (TIJ) or “Bubble Jet” technology developed mainly by the manufacturers Canon and Hewlett Packard, and Piezoelectric Ink Jet (PIJ) devices, as used for example by the manufacturers Epson and Tektronix.
While TIJ and PIJ technologies have been developed to very high levels of performance since their introduction, MEMJET technology is able to offer significant advantages over these technologies. Potential advantages include higher speeds of operation and the ability to provide higher resolution than obtainable with other technologies. Similarly, MEMJET Technology provides the ability to manufacture monolithic printhead devices incorporating a large number of nozzles and of such size as to span all or a large part of a page (or other print surface), so that pagewidth printing can be achieved without any need to mechanically traverse a small printhead across the width of a page, as in typical existing inkjet printers.
It has been found difficult to manufacture a long TIJ printhead for full-pagewidth printing. This is mainly because of the high power consumption of TIJ devices and the problem associated therewith of providing an adequate power supply for the printhead. Similarly, waste heat removal from the printhead to prevent boiling of the ink provides a challenge to the layout of such printhead. Also, differential thermal expansion over the length of a long TIJ-printhead may lead to severe nozzle alignment difficulties.
Different problems have been found to attend the manufacture of long PIJ printheads for large- or full-page-width printing. These include acoustic crosstalk between nozzles due to similar time scales of drop ejection and reflection of acoustic pulses within the printhead. Further, silicon is not a piezoelectric material, and is very difficult to integrate with CMOS chips, so that separate external connections are required for every nozzle.
Accordingly, manufacturing costs are very high compared to technologies such as MEMJET in which a monolithic device may be fabricated using established techniques, yet incorporate very large numbers of individual nozzles. Reference should be made to the aforementioned PCT application for detailed information on the manufacture of MEMJET inkjet printhead chips; individual MEMJET printhead chips will here be referred to simply as printhead segments. A printhead assembly will usually incorporate a number of such printhead segments.
While MEMJET technology has the advantage of allowing the cost effective manufacture of long monolithic printheads, it has nevertheless been found desirable to use a number of individual printhead segments (CMOS chips) placed substantially end-to-end where large widths of printing are to be provided. This is because chip production yields decrease substantially as chip lengths increase, so that costs increase. Of course, some printing applications, such as plan printing and other commercial printing, require printing widths that are beyond the maximum length that is practical for successful printhead chip manufacture.
SUMMARY OF THE INVENTION
The present invention is broadly directed to the provision of a suitable printhead segment support structure and ink supply arrangement for an inkjet printhead assembly capable of single-pass, full-page-width printing as well as to such printhead assemblies. While the invention was conceived in the context of MEMJET printhead segments (chips), and thus the following summary and description of the invention is provided with particular reference to printhead assemblies incorporating MEMJET printhead segments, it is believed that the invention also has the potential to be employed with other ink jet printhead technologies.
Accordingly, it is one object of the present invention to provide a printhead segment support structure that is capable of accommodating a series of printhead segments as described in PCT/AU98/00550 in an array that permits single-pass pagewidth printing across the width of a surface passing under the printhead assembly.
The term “single-pass pagewidth printing” should here be understood as referring to a printing operation during which the printhead assembly is moved in only one direction along or across the entire width or length of any print surface, as compared to a superimposed, generally orthogonal printhead carriage movement as employed in conventional ink jet printers. (Of course, printhead assembly movement may be relative, with the surface moving past a stationary printhead assembly.) It will be also understood that there are many possible page widths and the inkjet printhead segment support structure of the invention would be suitable for adaptation to a range of widths. A printhead assembly in accordance with the invention should in particular be useful where a plurality of generally elongate, but relatively small printhead segments are to be used to print across substantially the entire width of a sizable surface without the need for mechanically moving the printhead assembly or any printhead segment across as well as along the print surface.
The invention has also been conceived in light of potential problems related to the relatively small size of individual printhead segments, their fragility and the required highly accurate alignment or registration of individual printhead segments with each other on the support structure and with external components in order to provide a printhead assembly capable of single-pass, full pagewidth printing. Multiple ink supply channels are required to supply ink in reliable manner to all printhead segments. Because of the small size of the segments, this in general would require high quality micro-machined parts. An ink supply conduit, on the other hand, is most economically made if it can be formed at a much coarser scale.
Accordingly, another object of the invention is to provide a printhead segment support structure with a print fluid supply arrangement that ensures adequate print fluid (e.g. ink) supply to individual printhead segments mounted to the support structure, at an affordable manufacturing cost.
Typical MEMJET printhead segments have a dimension of 2 cm length by 0.5 mm width, and will include (in a layout for 4-color printing) four lengthwise-oriented rows of ink ejection nozzles, the segment being of monolithic fabrication. Longer segments could be made and used, but the size mentioned gives very satisfactory fabrication yields. Each printhead segment has ink inlet holes arrayed on one surface and corresponding nozzle outlets arrayed on an opposite surface. Each of the four rows will then require connection to an appropriate ink supply, such that an inkjet printhead assembly can be provided for operation with (for example) cyan, magenta, yellow and black inks for color printing.
Accordingly, yet a further object is to provide an ink supply arrangement thereby to enable supply of a number of differently colored inks (or other printing fluids) to selected ink inlets of individual printhead segments carried on a support structure for full pagewidth color printing.
Another related object of the invention is to provide a print fluid supply arrangement that is simple in layout and thus easy to incorporate in a printhead support structure. It should ensure even and reliable distribution of print fluids in a pagewidth inkjet printhead assembly.
In a first aspect, the invention provides a support for a plurality of inkjet printhead segments, said support including:
a hollow elongate member having at least one ink supply channel formed therein, the, or each, ink supply channel being in fluid communication with an elongate slot in and extending at least partly along the elongate member; and
a plurality of printhead segment carriers received and secured in neighbouring arrangement within the slot, each printhead segment carrier being adapted for mounting thereto of at least one printhead segment.
Each printhead segment carrier may include at least one ink gallery that is in fluid communication with said, or an associated one of said, ink supply channels when mounted to that printhead segment carrier.
The printhead segment carriers may be configured so that when the printhead segments are mounted in the printhead segment carriers they define a series of printing ranges in a direction lengthwise along the elongate member that overlap to define a combined printing range of greater lengthwise extent than any of the printing ranges of the respective printhead segments.
The printhead segment carriers may be substantially identical to one another and may have stepped terminal ends thereby to enable neighbouring pairs of printhead carriers to be mounted within the slot in a staggered manner.
Each printhead segment carrier may have an elongate recess in an external surface of the carrier within which at least one printhead segment is mountable and wherein recesses of neighbouring pairs of carriers overlap in a direction along the elongate member.
Each printhead segment carrier may define an elongate ink delivery slot that opens into said recess of each printhead segment carrier. Each ink delivery slot may be in fluid communication with a respective ink supply channel via said ink gallery that extends from said at least one ink slot to an opening in a rear face of the printhead segment carrier.
A plurality of said ink galleries and said openings may be in fluid communication with the, or each, ink delivery slot. Said openings associated with the, or each, said ink delivery slot may be arranged in a row extending in a direction along the elongate member.
Each printhead segment carrier may have a plurality of ink supply channels and a plurality of said rows of openings. Each row of openings may be aligned along its length with one said ink channel for passage of ink from said ink channel through said row of openings.
The ink galleries may be defined by a plurality of parallel walls extending transversely in each printhead segment carrier and intersecting with a plurality of converging walls extending from the rear face to shaped inner edges that at least partially define the ink delivery slots.
The assembly may include a shim that is shaped to be received in the slot in the elongate member and to lie between the elongate member and said printhead segment carriers, said shim having at least one aperture therein to permit flow of ink between the or an associated one of said ink supply channels and a corresponding one ink gallery of the respective printhead segment carrier.
The shim and the slot may be substantially semi-circular in cross-sectional shape.
The shim and/or the elongate member may comprise means for snap-fittingly mounting said shim at said slot. In another example, the shim may be adhesively bonded to mating surfaces of the elongate member. In yet another example, the printhead segment carriers may be adhesively bonded to the shim.
Webs, which abut external surfaces of the elongate member, may be attached to edges extending in a direction along the shim.
Each printhead segment carrier may have a recess formed in an external surface thereof within which at least one printhead segment is received when mounted to the printhead segment carrier. Said external surface may have a second recess formed therein and adapted to receive at least a part of a power or signal conductor terminating on the or one said printhead segment mounted to the printhead segment carrier.
Said conductor may comprise a tape automated bonded (TAB) film.
Said tape automated bonded film (TAB) may be wrapped around an external surface of the elongate member and terminated on a printed circuit board secured to a side of the elongate member opposite to the printhead segment to which it is connected.
The support assembly may include a first cap secured to a first terminal end of the elongate member and may have an ink inlet port in fluid communication with the or an associated one of said ink supply channels.
The support assembly may further include a second cap secured to a second terminal end of the elongate member and having an opening for bleeding of air from the or an associated one of said ink supply channels. Means for sealing off said opening after such bleeding may be provided.
Said second cap may include an outer face with a tortuous channel formed therein. Said tortuous channel may be in fluid communication with said opening and said sealing means may include a film removable at least in part from the outer face and adapted to adhere to the outer face thereby to cover the tortuous channel and seal off the opening. The support assembly may further include an external protective shield plate covering the printhead segment carriers and having openings arranged to permit unimpeded passage of ink ejected from nozzles of printhead segments mounted to the carriers towards a surface passing beneath the support assembly.
The elongate member may have three, four or six of said ink supply channels, one each for differently colored ink.
Each printhead segment carrier may be mounted within the slot at a longitudinal position within a predetermined distance of a designated longitudinal position of the carrier corresponding to a designated longitudinal position within the slot of a printhead segment when mounted to said printhead segment carrier.
The elongate member may be of substantially constant cross-sectional shape along its entire length.
In cross-section, the elongate member may include a peripheral structured wall including a base wall section, and side wall sections standing out from opposite edges of said base wall section, and wherein said slot lies between free edges of said side wall sections.
Said elongate member may further include at least one internal web extending from the base wall section and along said elongate member.
Said elongate member may have a plurality of said internal webs. In cross-section, said free edges of the side wall sections and free edges of said internal webs may lie on a semicircle and may define boundaries of said slot so that said slot is of semicircular cross-section.
In a second aspect, the invention provides an inkjet printhead assembly including:
a hollow elongate member having at least one ink supply channel formed therein, the or each ink supply channel being in fluid communication with an elongate slot in and extending at least partly along the elongate member; and
a plurality of printhead segment carriers received and secured in neighbouring arrangement within the slot; and
at least one printhead segment mounted to each printhead segment carrier.
Thus, the second aspect of the invention is directed to a printhead assembly that includes the support assembly of the first aspect of the invention.
It is preferred that the at least one printhead segment on each printhead segment carrier has a defined printing range in a direction lengthwise along the elongate member, and that the printing ranges of the printhead segments mounted to a plurality of adjoining printhead segment carriers overlap, so that the printhead segments mounted to said plurality of adjoining printhead segment carriers have a combined printing range of greater lengthwise extent than any of the printing ranges comprised therein. This is a suitable way in which printing may be accomplished on a surface without the presence of gaps corresponding to lengthwise gaps between individual printhead segments.
In a further aspect, the invention provides a method for assembling the inkjet printhead assembly wherein the step of mounting to each printhead segment carrier its respective at least one printhead segment precedes the step of securing that printhead segment carrier within the slot. It is then preferred that the printhead segment carriers are secured within the slot sequentially, and that the at least one printhead segment in each printhead segment carrier installed after the first is positioned longitudinally relative to the at least one printhead segment in the printhead segment carrier last installed before being finally secured and immobilized within the slot. Thus, accurate relative positioning of successive printhead segments lengthwise along the elongate member can be achieved.
Other aspects, objects and advantages of the invention, in its different embodiments, will also become apparent from the description given below of preferred embodiments and from the appended claims.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a perspective view of one embodiment of an inkjet printhead assembly according to the invention;
FIG. 2 is a perspective view of the inkjet printhead assembly shown in FIG. 1 , with a cover component (shield plate) removed;
FIG. 3 is an exploded perspective view of a part only of the inkjet printhead assembly shown in FIG. 1 ;
FIG. 4 is a perspective partial view of a support extrusion forming part of the inkjet printhead assembly shown in FIG. 3 ;
FIG. 5 is a perspective view of a sealing shim forming part of the inkjet printhead assembly shown in FIG. 3 ;
FIG. 6 is a perspective view of a printhead segment carrier shown in FIG. 3 ;
FIG. 7 is a further perspective view of the printhead segment carrier shown in FIG. 6 ;
FIG. 8 is a bottom elevation of the printhead carrier shown in FIGS. 6 and 7 (as viewed in the direction of arrow “X” in FIG. 6 );
FIG. 9 is a top elevation of the printhead carrier shown in FIGS. 6 and 7 (as viewed in the direction of arrow “Y” in FIG. 6 );
FIG. 10 is a cross-sectional view of the printhead carrier of FIGS. 6 and 7 taken at station “B-B” in FIG. 8 ;
FIG. 11 is a cross-sectional view of the printhead carrier of FIGS. 6 and 7 taken at station “A-A” in FIG. 8 ;
FIG. 11 a is an enlarged cross-sectional view of the seating arrangement of a printhead segment at the print carrier as per detail “E” in FIG. 11 ;
FIG. 12 is a cross-sectional view of the printhead carrier of FIGS. 6 and 7 taken at station “D-D” in FIG. 8 ;
FIG. 13 is an external perspective view of an end cap of the inkjet printhead assembly shown in FIG. 1 ;
FIG. 14 is an internal perspective view of the end cap shown in FIG. 13
FIG. 15 is an external perspective view of a further end cap of the inkjet printhead assembly shown in FIG. 1 ;
FIG. 16 is an internal perspective view of the end cap shown in FIG. 15 ;
FIG. 17 is a perspective view (from the bottom) of the printhead assembly shown in FIG. 1 ;
FIG. 18 is a perspective view of a part assembly of a support profile and modified sealing shim which are alternatives to those shown in FIGS. 4 and 5 ;
FIG. 19 is a perspective view showing a molding tool and illustrating the basic arrangement of die components for injection molding of the printhead carrier shown in FIGS. 6 and 7 ;
FIG. 20 is a schematic cross-section of the injection molding tool shown in FIG. 19 , in an open position; and
FIG. 21 is a schematic transverse cross-section of the injection-molding tool shown in FIG. 19 , in a closed position, taken at a station corresponding to the station “A-A” in FIG. 8 .
DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 shows in perspective view an inkjet printhead assembly 1 according to one aspect of the invention and, in phantom outline, a surface 2 on which printing is to be affected. In use, the surface 2 moves relative to the assembly 1 in a direction indicated by arrow 3 and transverse to the main extension of assembly 1 (this direction is hereinafter also referred to as the transverse direction of the assembly 1 ), so that elongate printhead segments 4 , in particular MEMJET printhead segments such as described in the above-mentioned PCT/AU98/00550, placed in stepped overlapping sequence along the lengthwise extension of assembly 1 can print simultaneously across substantially the entire width of the surface. The assembly 1 includes a shield plate 5 with which the surface 2 may come into sliding contact during such printing. Shield plate 5 has slots 6 , each corresponding to one of the printhead segments 4 , and through which ink ejected by that printhead segment 4 can reach surface 2 .
The particular assembly 1 shown in FIG. 1 has eleven printhead segments 4 , each capable of printing along a 2 cm printing length (or, in other words, within a printing range extending 2 cm) in a direction parallel to arrow 7 (hereinafter also called the lengthwise direction of the assembly 1 ) and is suitable for single-pass printing of a portrait A4-letter size page. However, this number of printhead segments 4 and their length are in no way limiting, the invention being applicable to printhead assemblies of varying lengths and incorporating other required numbers of printhead segments 4 .
The slots 6 and the printhead segments 4 are arranged along two parallel lines in the lengthwise direction, with the printing length of each segment 4 (other than the endmost segments 4 ) slightly overlapping that of its two neighboring segments 4 in the other line. The printing length of each of the two endmost segments 4 overlaps the printing length of its nearest neighbor in the other row at one end only. Thus printing across the surface 2 is possible without gaps in the lengthwise direction of the assembly. In the particular assembly shown, the overlap is approximately 1 mm at each end of the 2 cm printing length, but this figure is by no means limiting.
FIG. 2 shows assembly 1 with the shield plate 5 removed. Each printhead segment 4 is secured to an associated one printhead segment carrier 8 that will be described below in more detail. Also secured to each printhead segment 4 is a tape automated bonded (TAB) film 9 , which carries signal and power connections (not individually shown) to the associated printhead segment 4 . Each TAB film 9 is closely wrapped around an extruded support profile 10 (whose function will be explained below) that houses and supports carriers 8 , and they each terminate onto a printed circuit board (PCB) 11 secured to the profile 10 on a side thereof opposite to that where the printhead segments 4 are mounted, see also FIG. 3 .
FIG. 3 shows an exploded perspective view of a part only of assembly 1 . In this view, three only of the printhead segment carriers 8 are shown numbered 8 a , 8 b and 8 c , and only the printhead segment 4 associated with printhead segment carrier 8 a is shown and numbered 4 a . The TAB film 9 associated therewith is terminated at one end on an outer face of the printhead segment 4 and is otherwise shown (for clarity purposes) in the unwound, flat state it has before being wound around profile 10 and connected to PCB 11 . As can be seen in FIG. 3 , printhead segment carriers 8 are received (and secured), together with an interposed sealing shim 25 , in a slot 21 of half-circular cross-sectional shape in profile member 10 as will be explained in more detail below.
FIG. 4 illustrates a cross-section of the profile member 10 (which is preferably an aluminum alloy extrusion). This component serves as a frame and/or support structure for the printhead segment carriers 8 (with their associated printhead segments 4 and TAB films 9 ), the PCB 11 and shield plate 5 . It also serves as an integral ink supply arrangement for the printhead segments 4 , as will become clearer later.
Profile member 10 is of semi-open cross-section, with a peripheral, structured wall 12 of uniform thickness. Free, opposing, lengthwise running edges 16 ′, 17 ′ of side wall sections 16 and 17 respectively of wall 12 border or delineate a gap 13 in wall 12 extending along the entire length of profile member 10 . Profile member 10 has three internal webs 14 a , 14 b , 14 c that stand out from a base wall section 15 of peripheral wall 12 into the interior of member 10 , so as to define together with side wall sections 16 and 17 a total of four (4) ink supply channels 20 a , 20 b , 20 c and 20 d which are open towards the gap 13 . The shapes, proportions and relative arrangement of the webs and wall sections 14 a - c , 16 , 17 are such that their respective free edges 14 a ′, 14 b ′, 14 c ′ and 16 ′, 17 ′, as viewed in the lengthwise direction and cross-section of profile member 10 , define points on a semi-circle (indicated by a dotted line at “a” in FIG. 4 ). In other words, an open slot 21 of semicircular cross-sectional shape is defined along one side of profile member 10 that runs along its extension, with each of the ink supply channels 20 a - d opening into common slot 21 .
Base wall section 15 of profile member 10 also includes a serrated channel 22 opening towards the exterior of member 10 , which, as best seen in FIG. 3 , serves to receive fastening screws 23 to fixedly secure PCB 11 onto profile member 10 in a form-fitting manner between free edges 24 (see FIG. 4 ) of longitudinally extending curved webs 107 extending from the base wall section 15 of profile member 10 .
Referring again to FIG. 3 , sealing shim 25 is received (and secured) within the half-circular open slot 21 . As best seen in FIGS. 3 and 5 , shim 25 includes four lengthwise extending rows of rectangular openings 26 that are equidistantly spaced in peripheral (widthwise) direction of shim 25 , so that three lengthwise-extending web sections 27 between the aperture rows (of which two are visible in FIG. 5 ) are located so as to be brought into abutting engagement against the free edges 14 a ′, 14 b ′ and 14 c ′ of webs 14 a , 14 b , 14 c of profile member 10 when shim 25 is received in slot 21 . As can be gleaned from FIG. 4 , the free edges 16 ′ and 17 ′ of side wall sections 16 , 17 of profile member 10 are shaped such as to provide a form-lock for retaining the lengthwise extending edges 28 of shim member 25 as a snap fit. In other words, once shim 25 is mounted in profile member 10 , it provides a perforated bottom for slot 21 , which allows passage of inks from the ink supply channels 20 a - d through apertures 26 in shim 25 into slot 21 . A glue or sealant is provided where shim webs 27 and edges 28 mate with the free edges 14 a ′, 14 b ′, 14 c ′, 16 ′ and 17 ′ of profile member 10 , thereby preventing cross-leakage between ink supply channels 20 a - d along the abutting interfaces between shim 25 and profile member 10 . It will be noted from FIG. 5 that not all apertures 26 have the same opening size. Reference numerals 26 ′ indicate two such smaller apertures, the significance of which is described below, which are present in each aperture row at predetermined aperture intervals. A typical size for the full-sized apertures 26 is 2 mm×2 mm. The shim is preferably of stainless steel, but a plastics sheet material may also be used.
Turning next to FIGS. 6-12 , these illustrate in different views and sections a typical printhead segment carrier 8 . Carrier 8 is preferably a single microinjection molded part made of a suitable temperature and abrasion resistant and form-holding plastics material. (A further manufacturing operation is carried out subsequent to molding, as described below.) As best seen in FIGS. 6 and 7 , the overall external shape of carrier 8 can be described illustratively as a diametrically slit half cylinder, with a half-circular back face 91 , a partly planar front face 82 and stepped end faces 83 . FIG. 8 shows a plan view of back face 91 and FIG. 9 shows a plan view of front face 82 .
Carrier 8 has a plane of symmetry halfway along, and perpendicular to, its length, that is, as indicated by lines marked “b” in FIGS. 8 and 10 which lie in the plane. Line “b” as shown in FIG. 8 extends in a direction that will hereinafter be described as transverse to the carrier 8 . (When the carrier 8 is installed in the assembly 1 , this direction is the same as the transverse direction of the assembly 1 .) Lines marked “c” in FIGS. 8 , 9 , 11 and 12 together similarly indicate the position of an imaginary plane which lies between two sections of the carrier 8 of different length and whose overall cross-sectional shapes are quarter circles. Line “c” as shown in FIG. 9 extends in a direction that will hereinafter be described as lengthwise in the carrier 8 . (When the carrier 8 is installed in the assembly 1 this direction is the same as the lengthwise direction of the assembly 1 .) These sections will hereinafter be referred to as the shorter and longer “quarter cylinder” sections 8 ′ and 8 ″, respectively, to allow referenced description of features of the carrier 8 .
Each stepped end face 83 includes respective outer faces 84 ′ and 85 ′ of quarter-circular-sector shaped end walls 84 and 85 and an outer face 86 ′ of an intermediate step wall 86 between and perpendicular to end walls 84 , 85 . This configuration enables carriers 8 to be placed in the slot 21 of profile 10 in such a way that adjoining carriers 8 overlap in the lengthwise direction with the step walls 86 of pairs of neighbouring carriers 8 facing each and overlapping. Such an “interlocking” arrangement is shown in FIG. 2 , wherein it is apparent that every one of the eleven (11) carriers 8 has an orientation, relative to its neighbouring carrier or carriers 8 , such that faces 84 ′ and 85 ′ of each carrier lie adjacent to faces 85 ′ and 84 ′, respectively, of its neighbouring carrier(s) 8 . In other words, each carrier 8 is so oriented in relation to its neighbouring carrier(s) as to be rotated relatively by 180° about an axis perpendicular to the face 82 . In essence, neighbouring carriers 8 will align along a common lengthwise-oriented plane defined between the step walls 86 of adjoining carriers 8 , shorter and longer quarter cylinder sections 8 ′ and 8 ″ of adjoining carriers 8 alternating with one another along the extension of slot 21 .
Turning now in particular to FIGS. 7 , 9 , 11 and 11 a , front face 82 of carrier 8 includes on the shorter quarter cylinder section 8 ′ a planar surface 81 . Formed in surface 81 are two handling (i.e. pick-up) slots 87 whose purpose is described below. On the longer quarter cylinder section 8 ″, front face 82 incorporates a mounting or support surface 88 recessed with respect to edges 89 of sector-shaped end walls 84 that are co-planar with the surface 81 . As best seen in FIG. 11 , mounting surface 88 recedes in slanting fashion from a point on the back face 91 of the longer quarter cylinder section 8 ″ towards an elongate recess 90 extending lengthwise between walls 84 . Recess 90 is of constant transverse cross-section along its length and is shaped to receive in form-fitting manner one printhead segment 4 . FIG. 11 a shows, schematically only, printhead segment 4 in position in recess 90 . Mounting surface 88 is provided to accommodate in flush manner with respect to the surface 81 the terminal end of TAB film 9 connected to printhead segment 4 , as is best seen in FIG. 3 . Due to the opposing orientations of neighbouring carriers 8 along the extension of assembly 1 , the TAB films 9 associated with any two neighbouring carriers 8 lead away from their respective segments 4 in opposite transverse directions, as can be seen in FIG. 2 .
Referring now to FIGS. 6 , 7 , 8 , 10 and 11 in particular, four rows of ink galleries or ink supply passages 92 a to 92 d of generally quadrilateral cross-section are formed within the printhead segment carrier 8 . The ink galleries 92 a to 92 d act as conduits for ink to pass from the ink supply passages 20 a to 20 d , respectively, via openings 26 in the shim 25 , to the printhead segment 4 mounted in recess 90 of the printhead segment carrier 8 . Galleries 92 a - 92 d extend in quasi-radial arrangement between the half-cylindrical back face 91 of carrier 8 and recess 90 located in the longer quarter cylinder section 8 ″ at front face 82 . The expression “quasi-radial” is used here because recess 90 is not located at a transversely central position across carrier 8 , but is offset into the longer quarter cylinder section 8 ″, so that the inner ends of galleries 92 a - 92 d are similarly off-set, as further described below. Each gallery 92 has a rectangular opening 93 at back face 91 . All rectangular openings 93 have the same dimension in a peripheral direction of face 91 and are equidistantly spaced around the periphery of back face 91 . Moreover, the openings 93 are symmetrically located on opposing sides of the boundary between shorter quarter cylinder section 8 ′ and longer quarter cylinder section 8 ″, as represented in FIG. 11 by the line marked “c”. All openings 93 in the shorter quarter cylinder section 8 ′ are of the same dimension, and equispaced, in the lengthwise direction. This also applies to the openings 93 in the longer quarter cylinder section 8 ″, except that openings 93 ′ in the longer quarter cylinder section 8 ″ which correspond to endmost galleries 92 a ′ and 92 b ′ are of smaller dimension in the lengthwise direction than the other galleries 92 a and 92 b , respectively.
By way of further description of how the galleries 92 a to 92 d are formed, printhead segment carrier 8 includes a set of five (5) quasi-radially converging walls 95 which converge from back face 91 towards recess 90 at front face 82 and two of which define the faces 81 and 88 . The walls 95 perpendicularly intersect seven (7) generally semi-circular and mutually parallel walls 97 that are equidistantly spaced apart in lengthwise extension of carrier 8 . Of walls 97 , the two endmost ones extending into the shorter quarter cylinder section 8 ′ provide the endwalls 85 of stepped end faces 83 , thereby defining twenty-four (24) quasi-radially extending ink galleries 92 a to 92 d , of quadrilateral cross-section, in four lengthwise-extending rows each of six galleries. The walls 97 are parallel to and lie between endwalls 84 .
FIG. 12 shows a cross-section through one of the lengthwise end portions of longer quarter cylinder section 8 ″ of carrier 8 . By comparison with FIG. 11 (which shows a cross-section through the main body of carrier 8 ), it will be seen that the quasi-radially extending walls 95 bordering end gallery 92 a ′ have the same shape as walls 95 which border galleries 92 a , whereas gallery 92 b ′ is bounded on one side by intermediate step wall 86 and by a wall 108 . FIG. 12 also shows a wall 111 and a wall formation 112 on the wall 86 , the purpose of which is explained below.
Converging walls 95 are so shaped at their radially inner ends as to define four ink delivery slots 96 a to 96 d which extend lengthwise in the carrier 8 and which open into the recess 90 , as best seen in FIGS. 11 and 11 a . The slots 96 a to 96 d extend between the opposite end walls 84 of longer quarter cylinder section 8 ″ and pierce through the inner parallel walls 97 , including the endwise opposite walls 97 which form the end walls 85 of the shorter cylinder section 8 ′. FIG. 12 shows how slots 96 a to 96 d extend and are formed within the end portions of the longer quarter cylinder section 8 ″, where the slots 96 a to 96 d are defined by the terminal ends of two of walls 95 , walls 108 , 111 and wall formation 112 , wall formation 112 in effect being a perpendicular lip of intermediate step wall 86 .
The widths and transverse positioning of the ink delivery slots 96 a to 96 d are such that when a printhead segment 4 is received in recess 90 , a respective one of the slots 96 a - 96 d will be in fluid communication with one only of four lengthwise oriented rows of ink supply holes 41 on rear face 42 of printhead segment 4 , compare FIG. 11 a . Each row of ink supply holes 41 corresponds to a row of printhead nozzles 43 running lengthwise along the front face 44 of printhead segment 4 . In the schematic representation of segment 4 in FIG. 11 a , the positions of holes 41 and nozzles are indicated by dots, with no attempt made to show their actual construction. Reference to PCT Application No. PCT/AU98/00550 will provide further details of the make-up of segment 4 . Accordingly, each of the ink galleries of a specific gallery row 92 a to 92 d is in fluid communication with one only of the rows of ink supply holes 41 . Once a printhead segment 4 is form fittingly received in recess 90 and sealingly secured with its rear face 42 against the terminal inner ends of walls 95 , and wall formations 108 , 111 and 112 (using a suitable sealant or adhesive), cross-communication and ink bleeding between slots 96 a - 96 d via recess 90 is not possible.
When a carrier 8 is installed in its correct position lengthwise in the slot 21 of profile 10 , compare FIG. 3 , each opening 93 in its back face 91 aligns with one of the openings 26 in the shim 25 . Smaller openings 26 ′ in the shim 25 correspond to openings 93 ′ of the smaller galleries 92 a ′ and 92 b ′ of carrier 8 . Therefore, each one of the ink supply channels 20 a to 20 d is in fluid communication with one only of the rows of ink galleries 92 a to 92 d , respectively, and so with one only of the slots 96 a to 96 d respectively and only one of the rows of ink supply holes 41 . A suitable glue or sealant is provided at mating surfaces of the shim 25 and the carrier 8 to prevent leakage of ink from any of the channels 20 a to 20 d to an incorrect one of the galleries 92 , as described further below. The symmetrical location (mentioned above) of openings 93 on back face 91 of carrier 8 , which is matched by the openings 26 in shim 25 , enables the carrier 8 to be received in the slot 21 in either of the two orientations shown in FIG. 3 , with in both cases each row of ink galleries 92 a to 92 d aligning with one only of the ink supply channels 20 a to 20 d.
As mentioned above, the longer quarter cylinder section 8 ″ of carrier 8 has two galleries 92 a ′ and 92 b ′ at each lengthwise end that have no counterpart in the shorter section 8 ′. These galleries 92 a ′ and 92 b ′ provide direct ink supply paths to that part of their associated ink delivery slots 96 a and 96 b located in the longer quarter cylinder section 8 ″, and thus to the ink supply holes 41 of the printhead segment 4 that are located near the lengthwise terminal ends of segment 4 when secured within recess 90 . There are no corresponding quasi-radial galleries to supply ink to the end regions of the slots 96 c and 96 d . However, it is desirable to provide direct ink supply to the end portions of the other two slots 96 c and 96 d as well, without reliance on lengthwise flow within the slots 96 c and 96 d of ink that has passed through galleries 92 c and 92 d respectively. This is ensured by provision of ink supply chambers 99 c and 99 d which are shown in FIG. 12 and which supply ink to the slots 96 c and 96 d , respectively. Chambers 99 c and 99 d are bounded by the walls 84 , 86 , and wall formations 108 , 111 and 112 , are open towards slots 96 c and 96 d , respectively, and are in fluid communication through holes 113 and 114 in an endmost wall 97 with endmost ones of ink galleries 92 c and 92 d , respectively. The holes 113 and 114 have outlines shaped to match the transverse cross-sectional shapes of the chambers 99 c and 99 d , respectively, as shown in FIG. 12 , and the means whereby holes 113 and 114 are formed is described below.
FIGS. 13 and 14 show a first end cap 50 , which is sealingly secured to an open terminal longitudinal end of profile member 10 , as may be seen in FIGS. 1 and 2 . Cap 50 is molded from a plastics material and it incorporates a generally planar wall portion 51 that extends perpendicularly to a lengthwise axis of profile member 10 . Four tubular stubs 55 a - 55 d are integrally molded with planar wall portion 51 on side 52 of wall portion 51 which will face away from support profile 10 when end cap 50 is secured thereto. On the planar wall side 53 which will face the longitudinal terminal end of support profile 10 (see FIG. 14 ), four hollow-shaped stubs 57 a - 57 d are integrally molded with planar wall portion 51 . As best seen in FIG. 14 , ink supply conduits 56 a to 56 d are defined within tubular stubs 55 a to 55 d respectively, extend through planar wall portion 51 , and open within shaped stubs 57 a to 57 d , respectively, located on the other sides of cap 50 .
The shape of each one of the insert stubs 57 a to 57 d , as seen in transverse cross-section, corresponds respectively to one of the ink supply channels 20 a to 20 d of support profile so that, when cap 50 is secured to the terminal axial end of support profile 10 , the walls of stubs 57 a - 57 d are received form-fittingly in ink supply channels 20 a - 20 d to prevent cross-migration of ink therebetween. The face 53 abuts a terminal end face of the profile 10 . Preferably, glue or a sealant can be applied to the mating surfaces of profile 10 and cap 50 to enhance the sealing function.
The tubular stubs 55 a - 55 d serve as female connectors for pliable/flexible ink supply hoses (not illustrated) that can be connected thereto sealingly, thereby to supply ink to the integral ink supply channels 20 a - 20 d of support profile 10 .
A further stub 58 , D-shaped in transverse cross-section, is integrally molded to planar wall portion 51 at side 53 . In completed assembly 1 , the curved wall 71 , semi-circular in transverse cross-section, of retaining stub 58 seals against the inside surface of shim 25 , with the terminal edge of shim 25 abutting a peripheral ridge 72 around the stub 58 . Preferably, to avoid cross-migration of ink among channels 20 a to 20 d , an adhesive or sealant is provided between the shim 25 and wall 71 . The stub 58 assists in retaining the shim 25 in slot 21 .
A second end cap 60 , which is shown in FIGS. 15 and 16 , is mounted to the other end of the profile 10 opposite to cap 50 . Cap 60 has insert stubs 67 a to 67 d and a retaining stub 68 identical in arrangement and shape to stubs 57 a to 57 d and stub 58 , respectively, of end cap 50 . Insert stubs 67 a to 67 d and retention stub 68 are integrally molded with a planar wall portion 61 , and in the completed assembly 1 seal off the individual ink supply channels 20 a - 20 d from one another, to prevent cross-migration of ink among them. Wall 77 of the retention stub 68 abuts the shim 25 in the same way as described above. A sealant or adhesive is preferably used with end cap 60 in the same way (and for the same purpose) as described above in respect of end cap 50 .
Whereas end cap 50 enables connection of ink supply hoses to the printhead assembly 1 , end cap 60 has no tubular stubs on exterior face 62 of planar wall portion 61 . Instead, four tortuous grooves 65 a to 65 d are formed on exterior face 62 , and terminate at holes 66 a to 66 d , respectively, extending through wall portion 61 . Each one of holes 66 a to 66 d opens into a respective one of the channels 20 a to 20 d so that when the cap 60 is in place on the profile 10 , each one of the grooves 65 a to 65 d is in fluid communication with a respective one of the channels 20 a to 20 d . The grooves 65 a - 65 d permit bleeding-off of air during priming of the printhead assembly 1 with ink, as holes 66 a - 66 d permit air expulsion from the ink supply channels 20 a - 20 d of support profile 10 via grooves 65 a - 65 d . Grooves 65 a - 65 d are capped under a translucent plastic film 69 bonded to outer face 62 . Translucent plastic film 69 thus also serves the purpose of allowing visual confirmation that the ink supply channels 20 a - 20 d of profile 10 are properly primed. For charging the ink supply channels 20 a - 20 d with ink, film 69 is folded back (as shown in FIG. 15 ) to partially uncover grooves 65 a - 65 d , so that displaced air may bleed out as ink enters the grooves 65 a - 65 d through holes 66 a - 66 d . When ink is visible behind film 69 in each groove 65 a - 65 d , film 69 is folded towards face 62 and bonded against face 62 to sealingly cover face 62 and so cap-off grooves 65 a - 65 d and isolate them from one another.
Referring to FIG. 17 (and see also FIGS. 3 and 4 ), the printed circuit board (PCB) 11 locates between edges 24 formed on profile 10 , and is secured by screw fasteners 23 which engage with the serrations in elongate channel 22 of support profile 10 . The PCB 11 contains three surface mounted halftoning chips 73 , a data connector 74 , printhead power and ground busbars 75 and decoupling capacitors 76 . Side walls 16 , 17 of support profile 10 are rounded near the edges 24 to avoid damage to the TAB films 9 when these are wound about profile 10 . The electronic components 73 and 76 are specific to the use of MEMJET chips as the printhead segments 4 , and would of course, if other another printhead technology were to be used, be substituted with other components as necessitated by that technology.
The shield plate 5 illustrated in FIG. 1 , which is a thin sheet of stainless steel, is bonded with sealant such as a silicon sealant onto the printhead segment carriers 8 . The shield plate 5 shields the TAB films 9 and the printhead segments 4 from physical damage and also serves to provide an airtight seal around the printhead segments 4 when the assembly 1 is capped during idle periods.
The multi-part layout of the printhead assembly 1 that has been described in detail above has the advantage that the printhead segment carriers 8 , which interface directly with the printhead segments 4 and which must therefore be manufactured with very small tolerances, are separate from other parts, including particularly the main support frame (profile 10 ) which may therefore be less tightly toleranced. As noted above, the printhead segment carriers 8 are precision injection micro-moldings. Moldings of the required size and complexity are obtainable using existing micromolding technology and plastics materials such as ABS, for example. Tolerances of +/−10 microns on specified dimensions are achievable including the ink supply grooves 96 a - 96 d , and their relative location with respect to the recess 90 in which the printhead segments 4 are received. Such tolerances are suitable for this application. Other material selection criteria are thermal stability and compatibility with other materials to be used in the assembly 1 , such as inks and sealants. The profile 10 is preferably an aluminum alloy extrusion. Tolerances specified at +/−100 microns have been found suitable for such extrusions, and are achievable as well.
FIGS. 19 , 20 and 21 are schematic representations only, intended to provide an understanding of the construction of an injection-molding die used in the manufacture of a printhead segment carrier 8 . A multi-part die 100 is used, having a fixed base die part 104 , which in use defines the face 82 , recess 90 and slots 96 a to 96 d of the carrier 8 , and a multi-part upper die part 102 . The upper die part 102 is closed against the base part 104 for molding, and includes a part 101 with multiple fingers 101 a , which in use form the galleries 92 b (including galleries 92 b ′) and parts 106 which are fixed relative to part 101 . Also included in the upper part 102 are die parts 103 which are movable relative to the part 101 and which have fingers 103 a to form the remaining galleries 92 a , 92 c and 92 d . Parts 103 seat against parts 106 when molding is underway. Spaces between the fingers 101 a and 103 a correspond to the walls 97 . In use of the die 100 , terminal tips of the fingers 101 a and 103 a close against blades 105 which in use form the ink supply slots 96 a - 96 d of carrier 8 and which are mounted to male base 104 to be detachable and replaceable when necessary. Base die part 104 also has inserts 104 a , which in use form the pickup slots 87 . Because zero draft is preferred on the stepped end faces 83 in this application, the die 100 also has two movable end pieces (not shown, for clarity) which in use of the die 100 are movable generally axially to close against the upper die part 102 and which are shaped to define the end faces 84 ′, 85 ′ and 86 ′ of carrier 8 . FIG. 21 shows a schematic transverse cross-section of the mold 100 when closed, with areas in black corresponding to the carrier 8 being molded.
As was mentioned above, the two opposite end portions of the larger quarter cylinder section of carrier 8 incorporate two ink supply chambers 99 c and 99 d (see FIG. 12 ) to provide ink to the ink supply slots 96 c and 96 d in that region of the carrier 8 . These chambers 99 c and 99 d and associated communication holes 113 and 114 in parallel walls 97 that lead into the neighbouring galleries 92 c and 92 d , are formed in an operation subsequent to molding, by laser cutting openings of the required shape in the end walls 84 and the neighbouring inner parallel walls 97 from each end. The openings cut in end walls 84 are only necessary so as to access the inner walls 97 , and are therefore subsequently permanently plugged using appropriately shaped plugs 115 as shown in FIG. 6 .
Extrusions usable for profile 10 can be produced in continuous lengths and precision cut to the length required. The particular support profile 10 illustrated is 15.4 mm×25.4 mm in section and about 240 mm in length. These dimensions, together with the layout and arrangement of the walls 16 and 17 and internal webs 14 a to 14 c , have been found suitable to ensure adequate ink supply to eleven (11) MEMJET printhead segments 4 carried in the support profile to achieve four-color printing at 120 pages per minute (ppm). Support profiles with larger cross-sectional dimensions can be employed for very long printhead assemblies and/or for extremely high-speed printing where greater volumes of ink are required. Longer support profiles may of course be used, but are likely to require cross-bracing and location into a more rigid chassis to avoid alignment problems of individual printhead segments, for example in the case of a wide format printer of 54″ (1372 mm) or more.
An important step in manufacturing (and assembling) the assembly 1 is achieving the necessary, very high level of precision in relative positioning of the printhead segments 4 , and here too the construction of the assembly 1 as described above is advantageous. A suitable manufacturing sequence that ensures such high relative positioning of printheads on the support profile will now be described.
After manufacture and successful testing of an individual printhead segment 4 , its associated TAB film 9 is bumped and then bonded to bond pads along an edge of the printhead segment 4 . That is, the TAB film is physically secured to segment 4 and the necessary electrical connections are made. The terms “bumped” and “bonded” will be familiar to persons skilled in the arts where TAB films are used. The printhead carrier 8 is then primed with adhesive on all those surfaces facing into recess 90 that mate and must seal with the printhead segment 4 , see FIG. 11 a , i.e. along the length of the radially-inner edges of walls 95 , 108 and 111 , the face of formation 112 and on inner faces of walls 84 . The printhead segment 4 is then secured in place in recess 90 with its TAB film 9 attached. Extremely accurate alignment of the printhead segment 4 within recess 90 of printhead segment carrier 8 is not necessarily required (but is preferred), because relative alignment of all segments 4 at the support profile 10 is carried out later, as is described below. The assembly of the printhead segment 4 , printhead segment carrier 8 and TAB film 9 is preferably tested at this point for correct operation using ink or water, before being positioned for placement in the slot 21 of support profile 10 .
The support profile 10 is accurately cut to length (where it has been manufactured in a length longer than that required, for example by extrusion), faced and cleaned to enable good mating with the end caps 50 and 60 .
A glue wheel is run the entire length of semi-circular slot 21 , priming the terminal edges 14 a ′, 14 b ′, 14 c ′ of webs 14 a - 14 c and edges 16 ′, 17 ′ of profile side walls 16 , 17 with adhesive that will bond the sealing shim 25 into place in slot 21 once sealing shim 25 is placed into it with preset distance from its terminal ends (+/−10 microns). The shim 25 is snap-fitted into place at edges 16 ′, 17 ′ and the glue is allowed to set. Next, end caps 50 and 60 are bonded into place whereby (ink channel sealing) insert stubs 57 a - 57 d and 67 a - 67 d are received in ink channels 20 a - 20 d of profile 10 , and faces 71 and 77 of retention stubs 58 and 68 , respectively, lie on shim 25 . This sub-assembly provides a chassis in which to successively place, align and secure further sub-assemblies (hereinafter called “carrier subassemblies”) each consisting of a printhead segment carrier 8 with its respective printhead segment 4 and TAB film 9 already secured in place thereon.
A first carrier sub-assembly is primed with glue on the back face 91 of its printhead segment carrier 8 . At least the edges of walls 95 and 86 are primed. A glue wheel, running lengthwise, is preferably used in this operation. After priming with glue, the carrier sub-assembly is picked up by a manipulator arm engaging into pick-up slots 87 on front face 82 of carrier 8 and placed next to the stub 58 of end cap 50 (or the stub 68 of cap 60 ) at one end of slot 21 in profile 10 . The glue employed is of slow-setting or heat-activatable type, thereby to allow a small level of positional manipulation of each carrier subassembly, lengthwise in the slot 21 , before final setting of the glue. With the first carrier subassembly finally secured to the shim 25 within the slot 21 , a second carrier sub-assembly is then picked up, primed with glue as above, and placed in a 180-degree-rotated position (as described above, and as may be seen in FIG. 3 ) next to the first carrier sub-assembly onto shim 25 and within the slot 21 . The second carrier sub-assembly is then positioned lengthwise so that there is correct lengthwise relative positioning of its printhead segment 4 and the segment 4 of the previously placed segment 4 , as determined using suitable fiducial marks (not shown) on the exposed front surface 44 of each of the printhead segments 4 . That is, lengthwise alignment is carried out between successive printhead segments 4 , even though it is the printhead segment carrier 8 that is actually manipulated. This relative alignment is carried out to such (sub-micron) accuracy as is required to match the printing resolution capability of the printhead segments 4 . Finally, the bonding of the second carrier sub-assembly to shim 25 is completed. The above process is then repeated with further carrier sub-assemblies being successively positioned, aligned, and bonded into place, until all carrier subassemblies are in position within the slot 21 and bonded in their correct positions.
The shield plate 5 has a thin film of silicon sealant applied to its underside and is mated to the printhead segment carriers 8 and TAB films 9 along the entire length of the printhead assembly 1 . By suitable choice of adhesive properties of the silicon sealant, the shield plate 5 can be made removable to enable access to the printhead segment carriers 8 , printhead segments 4 and TAB films 9 for servicing and/or exchange.
A sub-assembly of PCB 11 and printhead control and ancillary components 73 to 76 is secured to profile 10 using four screws 23 . The TAB films 9 are wrapped around the exterior walls 16 , 17 of profile 10 and are bumped and bonded (i.e. physically and electrically connected) to the PCB 11 . See FIG. 17 .
Finally, the completed assembly 1 is connected at the ink inlet stubs 55 a - d of end cap 50 to suitable ink supplies, primed as described above and sealed using sealing film 69 of end cap 60 . Power and signal connections are completed and the inkjet printhead assembly 1 is ready for final testing and subsequent use.
It will be apparent to persons skilled in the art that many variations of the above-described assembly and components are possible. For example, FIG. 18 shows a shim 125 that is substantially the same as shim 25 , including having openings 126 and 126 ′ corresponding to the openings 26 and 26 ′ in shim 25 , save for longitudinally extending rim webs 128 which, when the shim 125 is mounted to a support profile 110 , abut in surface-engaging manner against the outside of the terminal ends of side walls 116 , 117 of profile 110 instead of being snap-fittingly received between them as is the case with shim 25 . This arrangement permits wider tolerances to be used in the manufacture of the support profile 110 without compromising the mating capability of the shim 125 and the profile 110 .
In yet another possible arrangement, the shim 25 could be eliminated entirely, with the printhead segment carriers 8 then bearing and sealing directly on the edges 14 a ′- 14 c ′ and 16 ′, 17 ′ of the webs 14 a - 14 c and side walls 16 , 17 at slot 21 of support profile 10 .
It will be appreciated by persons skilled in the art that still further variations and modifications may be made without departing from the scope of the invention. The embodiments of the present invention as described above are in no sense intended to be restrictive.
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A printhead assembly comprises an elongate support structure; a series of side wall sections extending a length of the support structure and defining ink supply channels, edges of the walls delineating a gap; a plurality of carriers positioned end-to-end in the gap and supported by said edges of the walls, the carriers defining a recess and ink supply passages in fluid communication with the recess and the ink supply channels; and a printhead integrated circuit mounted in each recess to receive ink from the ink supply channels. The elongate support structure is configured to permit a printed circuit board (PCB) to be fastened to an outside of the support structure so that the PCB can be connected to the printhead integrated circuits.
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BACKGROUND OF THE INVENTION
The present invention relates to a process and an associated apparatus for the thermal regeneration of charged active coke or active carbon granulate, in which the granulate is heated within a heating zone in a travelling bed through direct loading by a heated partial stream of the expelled desorption gas.
A good heat transfer is attained in this process through the direct contact between the granulate and the heating gas. It is, however, disadvantageous that the desorption gas for its heating is diluted through the supply of a hot foreign gas and must therefore be concentrated before its further processing. Although the dilution is somewhat reduced by blowing a partial stream of the desorption gas after heating into the heating zone. Large volume streams must, however, be heated in this case.
It is also known how to regenerate activated carbon through indirect heating. Since the activated carbon in this case does not come into contact with the heating medium, a dilution of the desorption gas is avoided. On the other hand, the heat transfer is too unfavorable in this process.
The invention therefore again turns to the initially named process. It has the object of developing this process further in such a manner that the volume of the gaseous heating medium guided through the granulate heap is kept as small as possible.
SUMMARY OF THE INVENTION
This problem is solved according to the present invention by preheating the granulate immediately before the entry into the heating zone and cooling it immediately after the exit from the heating zone and employing a heat exchange medium separate from the medium flowing through the heating zone.
The amount of heat, which must be supplied to the heating zone through the heating medium, is lowered through the preheating of the granulate so that smaller volume streams are required. This means that the degree of dilution can be lowered when using a foreign gas. At the same time, care is also taken through the gas side separation of the preheating and cooling zone from the heating zone that no foreign gas gets from any other source into the desorption gas.
It is advantageous when the granulate in the preheating zone and in the cooling zone is guided through vertical channels and when the heat exchange medium is guided externally around these channels. Hereby, a secure separation of the gas atmosphere of this zone relative to the heating zone is attained. At the same time, a good heat transfer is still possible because of the relatively short paths between the heated walls and the individual granulate grains.
To improve the heat balance, an improved embodiment of the invention provides that the heat exchange medium is at first guided through the cooling zone and subsequently through the preheating zone. In this manner, the heat withdrawn through cooling again comes to benefit the granulate in the preheating zone.
The partial stream of the desorption gas can be heated by adding a hot gas generated in a combustion chamber before the entry into the heating zone. To keep the degree of dilution small, the combustion in the combustion chamber is performed nearly stoichiometrically and the hot gas is admixed to the desorption gas practically at flame temperature.
The heating of the partial stream of the desorption gas can also be undertaken by heating this partial stream of the desorption gas indirectly in a heat exchanger through the combustion gases of a combustion chamber, by supplying these combustion gases after leaving the heat exchanger to the preheating zone and by supplying the cool air flowing through the cooling zone as combustion air to the combustion chamber. A dilution is avoided entirely. The combustion takes place with an increased excess of air, where the heat exchange medium flowing through the cooling zone and the preheating zone is included in the heating of the desorption gas for an improvement of the heat balance.
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 its construction and its method of operation, together with additional objects and advantages thereof, will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a longitudinal section through an apparatus according to the invention with a flow diagram for the guidance of the heat exchange medium; and
FIG. 2 shows a longitudinal section through an apparatus with a flow diagram according to another embodiment.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The illustrated desorber serves for desorbing and/or regenerating of active carbon or active coke granulate charged with sulphur dioxide or other injurious substances from the flue gas desulphurization. It consists of a housing with vertical side walls 1, a head 2 constructed as hood and a bottom 3.
The housing in the upper part is traversed by vertical channels 4, through which the granulate to be treated trickles downwardly. In the present case, the channels are formed by pipes arranged at a spacing from one another. The intermediate space remaining free between the channels 4 is closed off towards the head 2 and towards the interior of the desorber through a respective metal closure plate 5. Cones are placed between adjacent channels 4 on the upper metal closure plate 5. These cones guide the granulate supplied through the inlet opening 6 in the head 2 of the desorber into the channels 4.
No channels are provided in the middle part 7 of the desorber. The granulate issuing from the channels 4 wanders through this middle part 7 as travelling layer. Channels 8, which in construction and arrangement correspond to the channels 4 in the upper part, are provided in the lower part of the housing.
A respective metal closure plate 9 seals the space between the channels 8 and the side walls 1 from to the middle part 7 and from the bottom 3. Arranged underneath each of these channels 8 is a removal device, through which the granulate is carried out in a controlled manner. The removal device expediently consists of a catching plate 10, which is arranged at a small spacing below each channel 8 and on which the granulate accumulates in piles. The catching plates 10 are carried by leaf springs 11 or linkage rods. The leaf springs 11 are connected with a thrust linkage 12, which is, for example, transversely displaceable through an eccentric. Upon actuation of the thrust linkage 12, the catching plates 10 are displaced out of their middle position, while the heaped granulate slides over the edge of the catching plate 10. The granulate removed from the channels 8 is carried away through an output device in the bottom 3 and employed anew for adsorption of injurious substances from waste gases.
The cross-sectional shape of the channels 4 and 8 can be as desired. Their shape and the spacing of two opposite walls arising therefrom results from the requirement that, for one thing, the free trickling of the granulate shall not be hindered by bridge formation and that the mean spacing of a granulate grain from the heated wall may not be too great. In the present case, tubes with an inside diameter of 90 to 130 millimeters are employed with a maximum grain diameter of 9 millimeters.
To bring the granulate to the temperature necessary for the desorption, a gaseous heating medium of about 550° C. is blown through a duct 13 into the middle part 7 of the desorber. The duct 13 is connected with roof-shaped components 14, which pass through the housing of the desorber transversely and which are open downwardly. The heating medium rises upwardly in counterflow to the travelling direction of the granulate and heats it. The desorption gases expelled during heating are caught through roof-shaped components 15 together with the heating medium at a temperature of 300° C. and drawn off with the aid of a fan 16 through the duct 17 connected with the roof-shaped components 15. A dust precipitator 18 in the dust 17 takes care of the separation of entrained dust. The mixture of desorption gas and heating medium is fed to a further processing step.
The middle part 7 of the desorber represents the heating zone. The generation of the heating medium blown into the heating zone can take place by feeding back a partial stream of the desorption gas through the duct 19. In that case, purely by computation, the quantity of the desorption gas carried in the cycle is greater than the quantity of gas which is expelled through the heating of the granulate. An inert hot gas is admixed to the partial stream before the entry into the heating zone. The hot gas is obtained in a gas heater 20 through nearly stoichiometric combustion of a gaseous fuel with air. This hot gas is fed into the duct 13 at flame temperature together with the partial stream of the desorption gas from the duct 19.
Two stubs 21 and 22 are connected to the lower part of the housing which is traversed by the channels 8 and represents the cooling zone. A gaseous cool heat exchange medium, for example air at ambient temperature, is guided through the stub 21 into the space externally of the channels 8. The medium flows through the space under multiple deflection at the metal deflecting plates 23 and in this manner cools the granulate trickling through the channels 8. The heated heat exchange medium, after leaving the cooling zone, is blown via a duct 24 through the inlet stub 25 into the upper part of the housing which represents the preheating zone. It flows through the space externally of the channels 4 while delivering heat to the granulate. The heat exchange medium is subsequently delivered to the surroundings as waste air through the outlet stub 26.
When using air as heat exchange medium, a partial stream of the medium leaving the cooling zone can also be fed as combustion air to the gas heater 20.
According to FIG. 2, the partial stream of the desorption gas is heated in directly in a heat exchanger 27. The heat exchanger 27 is loaded with flue gas from a combustion chamber 28. The combustion in the combustion chamber 28 is adjusted by excess of air so that the flue gases enter the heat exchanger 27 at a temperature of about 800° C.
The cooling air at a temperature of about 250° C. leaving the cooling zone through the stub 22 in the lower part of the desorber is for the largest part fed as combustion air to the combustion chamber 28. The cooling air not required is blown off. The flue gas, which after leaving the heat exchanger 27 displays a temperature of about 400° C., is inserted in the preheating zone through the entry stub 25 in the cutting part of the desorber. The flue gas is given off as waste gas after the heat delivery to the granulate.
The heat exchange medium, which within the preheating zone and the cooling zone circulates around the channels 4 and 8 from outside, is sucked through this zone. For this, a respective fan 29 and 30 is arranged in each duct which connects to the outlet stubs 26 and 22. In this manner, the risk of a fire is to be counteracted, which could arise when the heat exchange medium containing oxygen is forced into the granulate heap upon rupture of a channel wall.
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, and therefore, such adaptations should and are intended to be comprehended within the meaning and range of equivalence of the following claims.
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A process for thermal regeneration of charged activated coke or activated carbon granulate, in which the granulate is preheated in a preheating zone, and is then heated in a heating zone of a traveling bed by direct contact with a heated stream in the form of a partial stream of desorption gas expelled from the granulate. The granulate is then cooled in a cooling zone immediately after leaving the heating zone. The preheating and cooling procedures are carried out by using a heat exchange medium which is separate from the heated stream in the heating zone.
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FIELD
The present version of this device relates generally to the field of decorative jewelry and especially that of decorative interchangeable earrings, rings and pins.
BACKGROUND
This device relates to decorative jewelry, and more particularly to a device that allows a user to attach and customize decorative pieces to the ears, body or clothing where the jewelry will remain visible without flopping over and the mechanics not be seen as well.
Many people enjoy decorative jewelry and earrings and many also fashion their own jewelry to match various outfits, holidays or events. Many people also use decorative artificial floral jewelry. One of the problems with using decorative artificial floral jewelry is that many floral decorations are not rigid. This causes a problem in that the floral decorations especially those larger than a certain size, if attached at only one point, can flop over and become not entirely visible. This defeats the whole purpose of the decorative jewelry and earrings and can deter from the overall presentation to the public.
Many people enjoy fashioning their own decorative floral jewelry and there is a need to provide a device that will allow them to fashion their own custom colors and designs that will not flop over and will stay visible to provide the best presentation.
Fashion oriented people enjoy mixing existing jewelry and changing out portions of existing jewelry to create a different and new color or style of floral jewelry or earrings.
For the foregoing reasons, there is a need for a device that will allow users to create their own combinations of decorative jewelry and earrings especially those of the floral nature that will not flop over when affixed to the wearers body or clothing. There is also a need for a device that will allow crafters, custom jewelry makers and manufacturers to use non rigid floral pieces to create custom jewelry or earrings. There is also a need for a device that will allow the relative ease of swapping their custom pieces with other pieces for a different look, holiday theme or color combination.
SUMMARY
In view of the foregoing disadvantages inherent in the area of floral jewelry and earrings there is a need for a device that will allow a user to wear floral earrings or other jewelry. There is a need for a device that will allow a user to have a piece that they can interchange the elements of the jewelry for a custom look. There is a need for a device that will allow the floral decorative piece to remain fully open and not droop or sag.
A first objective is to provide a device that allows the use of non-rigid floral jewelry to remain visible.
Another objective is to provide a device that allows the interchangeability of floral jewelry products.
It is yet another objective to provide a device that allows customization of floral jewelry products.
It is a still further objective to provide a device that will not be too heavy to wear as an earring and still provide for full viewing of the floral portion.
These together with other objectives of this device, along with various features of novelty which characterize this device, are pointed out with particularity in the claims annexed hereto and forming a part of this disclosure. For a better understanding of this device, its operating advantages and the specific objectives attained by its uses, reference should be had to the accompanying drawings, claims and descriptive matter in which there is illustrated a preferred embodiment of the device.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 shows an exploded side view of one embodiment of a decorative earring.
FIG. 2 shows a front view of one embodiment of the front with rings attached.
FIG. 3 shows a front view of one embodiment of the base and clasp for the back of the floral element.
FIG. 4 shows a side detailed view of one embodiment of the holder and related elements that are attached to the back of the floral element.
FIG. 5 shows a side detailed view of another embodiment of the base and related elements that are attached to the back of the floral element with an alternative hinge.
FIG. 6 shows another embodiment of the decorative earring.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to the drawings in detail wherein like elements are indicated by like numerals, there is shown in FIG. 1 an exploded view of one embodiment of a decorative earring 12 . As can be seen, floral element 40 has a center 20 attached to the front 43 of floral element 40 .
The center 20 can be circular or any other shape to imitate the center portion of a flower. To the face 19 of the center 20 are attached a plurality of rings 18 . In this embodiment there are attached four rings 18 approximately evenly spaced around the edge of the center 20 . More or fewer rings 18 could be attached to the face 19 , see FIG. 2 .
The rings 18 allow for the attachment of strings of beads 15 and or pearls to coordinate with the color of the floral element 40 or to contrast with the floral element 40 . The whole center 20 can thereby be changed or swapped out with another embodiment of the center 20 for variety of look, color and appearance.
The floral element 40 is meant to imitate the petals of a flower. This floral element 40 could likewise be of any color, shape or design that was needed to imitate the petals of a real flower.
Other decorative elements besides or in combination with the beads 15 could also be attached to the rings 18 of the center 20 .
To the back 21 of the center 20 and approximately centered there upon is located a post 22 . Post 22 is long enough to be inserted into and through the floral element 40 , the base 26 and clasp 30 through post hole 36 and retaining hole 34 in clasp 30 to be retained in the post holder 32 .
The floral element 40 is made from any soft material that imitates a natural flower. The front 43 of the floral element 40 can have crushed sand or other precious or semi precious gem stones or crystals adhered there upon to enhance the look of the floral element 40 , or it can just be plain without these additional decorative elements. The floral element 40 has a hole 42 located at the floral center 41 .
To the back 45 of the floral element 40 is attached a base 26 , rod 28 , platform 24 and clasp 30 collectively referred to as holder 47 . The base 26 has a front 25 and a back 27 . This FIG. 1 shows the clasp 30 in the partially closed position. The clasp 30 rotates around the hinge 38 to open and close on the wearers ear lobe for example. This embodiment of the clasp 30 has a base 26 with a post hole 36 located approximately in the center large enough to allow the post 22 to pass through. In this embodiment, a pair of rods 28 are affixed to the back 27 of the base 26 , see FIG. 3 . The earring 12 is meant to be worn such that the rods 28 are located in an up orientation relative to the ground.
While this embodiment shows rods 28 that are straight, it should be understood that the rods 28 could be curved, s-shaped or other shapes to effectuate contact with the various petal shapes of the floral element 40 . It is the intent to provide an attachment point for the petals of floral element 40 and yet hide the rods 28 as much as possible, hence the need for possibly different shapes and lengths of rods 28 .
The rods 28 each have a platform 24 located at one end. While this embodiment shows the platform 24 to be circular and the rods 28 to be linear, it should be understood that platform 24 and rods 28 could be larger or smaller and either circular or of another shape. The shape/size of the platform 24 and rod 28 is dependent upon the size/shape of the petals of the floral element 40 . The platforms 24 and rods 28 are designed to provide the best support to the floral element 40 while staying as hidden as possible. Alternatively, there could be more than one platform 24 on the rod 28 and it is not necessarily limited to the end of the rod 28 as shown in this embodiment.
The hinge 38 is located near the bottom of the base 26 . A clasp 30 is interconnected to the hinge 38 , such that the clasp 30 rotates relative to the base 26 .
The platforms 24 and rods 28 are sized such that they can be affixed to the back 45 of the floral element 40 . This provides that when the earring 12 is affixed to an ear lobe for example (not shown), the portion of the floral element 40 that is attached to the platforms 24 on the rods 28 does not flop down and cover the beads 15 detracting from the look of these floral earrings 12 . The platforms 24 and rods 28 can be affixed to the back 45 of the floral element 40 with an adhesive or the platforms 24 and rods 28 could be affixed to the back 45 of the floral element 40 by any number of treatments such as heat, stitching and others.
The clasp 30 houses a post holder 32 . The post holder 32 is made from a soft pliable material. The clasp 30 has a post hole 36 there through and the post holder 32 has a retaining hole 34 which when the post holder 32 is affixed to the clasp 30 , both of these holes are collinear. Likewise, the post hole 36 , retaining hole 34 , floral center 41 are collinear. When the clasp 30 is affixed to a users earlobe for example, the post 22 , floral center 41 , post hole 36 , and retaining hole 34 are collinear. This allows post 22 to pass through the ear lobe into and through the base 26 , through the clasp 30 and be retained in the post holder 32 . This thereby affixes the earring 12 to the user's ear lobe.
This embodiment of the earring 12 shows two rods 28 . Other embodiments could have more or fewer rods 28 and any size or shape of the platform 24 and rods 28 dependent upon the size and design of the floral element 40 that needs to be supported.
FIG. 5 shows a side detailed view of another embodiment of the base 26 and related elements that are attached to the back 45 of the floral element 40 with a different type of hinge 38 mechanism. The hinge 38 would not have to be located at the bottom of the base 26 .
FIG. 6 shows another embodiment of the earring 12 . In this embodiment, the earring 12 has a hook 51 for insertion into the ears of those persons having pierced ears. A rod 28 provides support to the back of a decorative element 49 , in this embodiment a feather. It should be understood that while this embodiment shows a feather as decorative element 49 many other similar types of elements could be affixed in this position, such as cloth, lace, stone and many other light weight materials that would enhance the earring 12 .
The rod 28 is attached to the hook 51 with a clip 57 to insure that the decorative element 49 is and remains oriented correctly relative to the hook 51 and thereby the piercing in the ear, not shown. One end of the hook 51 has a loop 53 where the opposite end of the hook 51 gets inserted into the ear piercing. The hook 51 loop 53 is connected to a loop 53 of the rod 28 . The opposite of end of the rod 28 can have a platform 24 , this embodiment shows a loop by way of example and not by limitation.
The decorative element 49 connects to a retention device 55 which holds the decorative element in a fixed position relative to the retention device 55 and thereby the hook 51 and piercing in the ear. The retention device 55 has a loop 53 on one end.
The decorative element 49 can be attached to rod 28 and platform 24 by any suitable adhesive for the stability of decorative element 49 .
The loops 53 of the hook 51 , rod 28 and retention device 55 are interconnected. As an alternative, a second rod 28 ′ with loop 53 could also be connected at this junction. Rod 28 ′ could likewise hold decorative elements 49 , in this embodiment are shown beads—by way of example and not a limitation, to further enhance the decorative appeal of the earrings 12 .
It will now be apparent to those skilled in the art that other embodiments, improvements, details and uses can be made consistent with the letter and spirit of the foregoing disclosure and within the scope of this application, which is limited only by the following claims, construed in accordance with the patent law, including the doctrine of equivalents.
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A decorative floral jewelry device is shown. The device allows the user to change out the beaded center portion of the floral jewelry and also provides at least one rod with platform that affixes to the back of the floral element such that the floral element does not sag thereby deterring from the look of the jewelry. An alternative embodiment shows a jewelry device that has a rod with platform and loop but uses a hook with loop a retention device and clip to fasten a decorative element.
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FIELD OF THE INVENTION
This invention relates to a new improved polycentric variable axis hinge. More particularly, this invention relates to a hinge having improved extension and flexion movement, which is especially useful when incorporated as the pivotal system in the design of orthotic devices. Of special utility is the use of the novel polycentric variable axis hinge in hinged knee-joint supports or more involved functional knee braces.
BACKGROUND AND PRIOR ART
Knee braces are known in the prior art. The movement of the knee joint is limited in certain cases, but in almost every instance the braced knee is permitted some movement. The knee-joint is made up of two condyloid joints and a third joint, partly arthrodial, but not completely, since the articular surfaces are not mutually adapted to each other. The resulting movement is not a simple gliding motion. The principle movements that take place at the knee joint are flexion and extension.
The movements of flexion and extension at this joint differ from those in a typical hinged joint, such as the elbow or hip. The axis around which motion takes place in the knee joint is not fixed, but the axis shifts forward during extension, as the gliding movement is superimposed on the rolling motion and the axis shifts backward during flexion.
Although the knee joint has been described as a hinged joint in the prior literature; it has a more complicated character. The knee joint must be regarded as consisting of three articulations, of two different kinds. The first is a condyloid articulation; in this form of the joint, an ovoid articular surface, or condyle, is received into an elliptical cavity in such a manner as to permit flexion, extension, abduction, adduction, and circumduction, but no axial rotation. The second kind of articulation involved is arthrodial; this is a joint which permits only gliding movement. It is formed by the apposition of plane surfaces, or one slightly concave, the other slightly convex. The amount of motion between these surfaces is limited by the ligaments or osseous processes surrounding the articulation.
When damage or injury occurs to the knee joint some form of suitable bracing is required. Associated with the bracing, in order to permit movement, as flexion and extension of the knee joint, there is a hinged structure pivotal about the knee joint.
Previous known knee braces and protective devices contain simple hinged structures or more recently a biaxial hinge. All of the previously designed hinges attempted to parallel the complex movement of the knee joint. Some knee braces for support and protection of the knee joint incorporate both an inner and an outer bracing structure.
Anderson, U.S. Pat. No. 4,249,524, discloses a true biaxial or double hinged pivotal brace and knee stabilizer. McDavid, U.S. Pat. No. 3,528,412, describes a brace with a fixed single pivot hinge. Rigdon, U.S. Pat. No. 4,219,892, discloses a knee brace having an accordian-folded section filled with fluid and held together with tension straps.
French Patent Application No. 79-10960 discloses a "link" hinge. The intermediate link has a longitudinal slot, the slot allows one of the uprights to move only in the direction of the longitudinal axis. The other end of the link has a fixed pivot to which is connected the other upright or brace extension. Canadian Pat. No. 1,011,204 relates to a knee brace with a dual planer link element between the elongated upper and lower arms of the brace. The arm and connecting link are essentially planer and are limited in pivotal motion to the plane of the link element and the front and back stops of the link element has an upper and lower pivot points spaced apart by a distance range of about 3/4 of an inch to about 2 inches.
Frank, U.S. Pat. No. 4,340,041, relates to an articulate splint having upper and lower anchor bars connected to a lock plate. The lock plate contains a hinge means. The hinge means in the lock plate has a single pivotal axis. Taylor, U.S. Pat. No. 3,902,482, describes a mechanical joint for orthopedic braces or prosthesis. The joint has an upper and lower portion attached by a link. Each portion has dual bearings which combine to provide a pivotal movement closely simulating the flexing action of a knee.
Meany, U.S. Pat. No. 2,460,895, relates to a joint protector having a longitudinally movable hinged joint; one fixed pivotal end, and one pivotal and longitudinally sliding connection. Goodwin, U.S. Pat. No. 58,403, relates to a surgical splint with a movable hinge having a set-screw moving in a slot and a single fixed pivot. Barry, U.S. Pat. No. 1,374,177, relates to an orthopedic appliance having a free pivotal connection and a means for fixing the connection so as to form a rigid structure. There is no provision for movement.
Rossman, U.S. Pat. No. 3,581,741, relates to a partially leg encircling knee brace with a hinge means on the upper inside body portion which includes a single rivet and a single pivot pin or rivet connecting a bar between the upper hinge and the lower body portion of the brace. Clegg, U.S. Pat. No. 901,592, relates to bracing device with a single pivot in conjunction with slide button in the slot which together allow vertical movement as well as single point pivot. Peckham, U.S. Pat. No. 2,467,907, describes a knee brace having springs pivotally attached top and bottom to two centrally disposed shaped plates on the inside and outside of the knee joint. In effect each pivot point is a rotary pivot at a single point. Peckham, U.S. Pat. No. 3,194,233, relates to a corrective and protective knee brace which has a pair of curved pressure members on opposite sides of the knee joint. The curved pressure members contain hinge joints which are made up of conventional hinge parts.
McClure, U.S. Pat. No. 3,350,719, relates to a knee brace having an upper bar and a lower bar which are pivotally joined with a hinge arrangement. The hinge in McClure is a link bar with an upper pivot pin and a lower pivot pin. The pivot pin provides a double conventional pivoting hinge joint connecting the upper brace bar and the lower brace bar through the link bar.
Each of the prior art hinges associated with the knee braces or protective devices, includes a simple pivoting hinge, either alone as a single pivot point or a pair of single pivot points spaced apart or in close proximity. All of the prior braces attempt to provide a hinge device to emulate and move parallel to the complex movement of the knee joint. Some braces are in place when the leg is extended, but fail to accurately follow the knee motion when flexed.
SUMMARY OF THE INVENTION
A principle object of this invention is to provide a new variable axis pivotal joint system for use in knee braces, protective devices and other similar orthotic devices so constructed to accurately follow the complex movement of the knee joint and similar human and animal body joints.
Another object of the invention is to provide a polycentric variable axis pivotal joint system which can be adjusted to control extension and flexion to accommodate symptomatic or rehabilative instabilities.
A further object is the provision of a polycentric variable axis pivotal joint system which is constructed to allow only pivotal movement and not lateral movement of the hinged body joint.
Other important objects and purposes of the instant invention will be disclosed and apparent in the following detailed description and the specification and the drawings to which reference is made.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a planer view of the variable axis pivotal hinge system in the extended position.
FIG. 2 is a planer view of the variable axis pivotal hinge system in the flexion position.
FIG. 3 is a side view showing the construction of the variable axis pivotal hinge system of FIG. 1.
FIG. 4 is an exploded side view of the variable axis pivotal hinge showing the elements of construction and their assembly.
DESCRIPTION OF THE INVENTION
With reference to the drawings, FIGS. 1-4, the polycentric variable axis pivotal hinge of the present invention comprises an upper extension 1 and a lower extension 2 secured together by the variable axis hinge. Each extension has a complementary angular offset to keep the extensions in parallel, offset planes and yet incorporate the hinge.
As best illustrated in FIG. 4, it will be seen that the upper extension 1 is angularly offset at its upper portion 11 and maintains this offset configuration down to a point just before the hinge as indicated at 15. A similar complementary configuration is indicated for the lower extension 2 at 12 and 14. Angular interconnecting means 17 and 18 displace the hinge outward from the body joint and each secures a portion of the hinge at 20 and 21.
The polycentric variable axis hinge is made up of a central member 30, which is substantially a flat oval or semicircular or elliptical flat disk-like plate, having an inside surface and an outside surface, and an upper end and a lower end. Said central member is interiorly disposed in an overlying relationship with respect to each lower terminal ends 31 and 32 of the upper extension 1 and the lower extension 2, respectively. The central member 30 is provided with three equally spaced openings: two outer openings along the same axis are holes 41 and 42, one on the upper end and one on the lower end, and a central opening 43 which is an elongated slot equally spaced between the outer openings 41 and 42 perpendicular to the axis on which the outer openings lie.
In the terminal ends 31 and 32 of the upper extension 1 and lower extension 2 each are provided with a short horizontal slot, 22 and 23, opening parallel to the central axis of the angle of offset from the main extensions 11 and 12. The offset of the terminal ends is angular to the longitudinal axis of the extension. Also provided is an annular opening in each of the terminal ends 31 and 32 at 20 and 21 spaced from the horizontal slots 22 and 23 and on the same axis as the horizontal slots 22 and 23.
The central member 30 is interiorly interposed between the lower terminal ends 31 and 32, such that an upper pivot rivet-pin 44 can extend through the mating opening 21 in the lower terminal end 31 and through the mating opening 41 in the central member and is terminated on the outside surface of the central member by a terminating means, such rivet-pins. In a similar manner a pivot pin 45 extends through the mating opening 20 in the lower terminal end 32 and through the mating opening 42 in the central member and is terminated on the inside surface of the central member.
The pivot pins 44 and 45 provide a means for pivotally connecting the upper extension 1 and the lower extension 2 to the central member. A guide pin follower 50 extends pivotally and glidably through the slot 23 in the lower terminal end 31 of upper extension 1, through vertical slot 43 in the central member 30 and through slot 22 in the lower terminal end 32 of lower extension 2. The terminal ends 31 and 32 in which the slots 22 and 23 are located are angled toward the full extension configuration. As shown in FIG. 1. At this extended position the guide pin follower is at the top of the slot 43 in the central member. The upper extension 1 and lower extension 2 are longitudinally aligned with each other and with the central member. The top of the vertical slot 43 in the extended position acts as a stop when the guide pin follower 50 engages the top of the slot, in this way further rotation which results in hyperextension is prevented. The pivotal movements of the upper and lower extensions are limited, so that when they have rotated in a longitudinally aligned position simulating the thigh and calf of the leg when they are aligned in standing position. However, pivotal movement of the upper and lower extension 1 and 2 in the opposite direction is limited only by the flexural limits of the knee joint.
By having a common guide pin follower 50 coacting with the central member 30 and interactive pivots at 20 and 21, which also coact with the central member, there is provided in essence a triaxial hinge. Such a triaxial hinge more naturally follows the complex movement of the human knee. The variable axis hinge action provided when the instant hinge is incorporated into a knee brace in which the upper and lower extensions are approximately laterally aligned with the pivotal portions of end of the femur and the end of the tibia, respectively, affords a very accurate approximation of the true knee action. Thus, in this hinge, the upper extension 1 simulates the action of the femur and the lower extension 2 simulates the action of the tibia. The central member 30 spans the joint space and is connected to each extension 1 and 2 by one individual pivot pin each 44 and 45, and one common guide pin follower 50 in order to simulate the complex pivotal hinge action of the knee.
In its operation and movement from extension to flexion the hinge displays a variable axis with continuously changing central pivot point as the guide pin follower 50 moves within the slot 43 in the center member 30. The slot 43 acts as a guide means for receiving and cooperating with the guide pin follower 50. The movement of the hinge defines the extension and flexion of the extensions 1 and 2. Said guide pin follower causes the motion to be transmitted to angular rotation and pivot about each of the extensions 1 and 2. The pivotal action for each extension is centered on the axis of the pivot points 20 and 21. The slot in each angular terminal portion of the extensions permits the angular motion to follow the horizontal movement of the guide pin follower. Each extension moves in a relative angular movement determined by the coaction of the guide pin follower interacting with the slots in the angular terminal portions of the extensions and the guide pin follower moving in the horizontal slot in the central member. In the central member the spatial placement of the pivot points are spaced apart and equidistant from the central vertical slot, which is perpendicular to the longitudinal axis of the pivot points 41 and 42.
Bushing members formed separately from the pivot or pin are used in the hinge to cooperate with the pivot or pin and further assist in the ease of movement of the various members of the instant hinge. Since the movement and relative ease of movement is important for the successful acceptance of the device by potential users. Alternative, to the use of bushings for the pivot pins is the use of washers or gaskets placed between the pivot pin head or terminal portion and the surface immediately registerable with said pivot pin or rivet head or terminal portion. Also bushings or washers maybe placed between registerable surfaces, as between the extension terminal portion and the central member.
A series of spaced holes 61-68 are provided in the central member 30 for insertion or adaption of bumpers or stops or limit the extent of pivot movement. Hence the bumpers or stops are adapted to engage the lower terminal ends 31 and 32 of the upper and lower extensions and prevent the further movement of the extensions. Hyperextension and excessive flexion by the knee is prevented by use of said bumpers or stops placed in holes 61 through 68. The bumpers or stops may be set screws or the like placed in threaded holes. Thus, the hinge imposes no vertical axial restraint unless said bumper or stop is in place. The only other restraint is the guide pin follower 50 within the slot 43 as described above, when the guide pin 50 engages the top extreme of the slot 43. The hinge imposes restraint in compression, and no stress when the knee is flexed.
The present polycentric variable axis hinge is very compact and light in weight. It may be made of a light metal or alloy, or it may be made of a rigid plastic material.
Preferably, the material of construction is stainless steel. The upper and lower extensions may be covered or placed in a soft resilient covering--woven, knitted or one or two way stretch fabric, sponge rubber or similar resilient material sleeves and secured therein by stitching or adhesive or both. These features adapt the hinge to comfort of the user. For certain other uses the extensions may be embedded in plastic or plaster of Paris for fitting to the users leg or the like.
It will be apparent to those skilled in this art that various changes may be made in the invention without departing from the spirit and scope thereof, and therefore the invention is not limited by that which is shown in the drawings and described in the specification, but only as indicated and defined in the appended claims.
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A polycentric variable axis pivotal hinge system especially designed and adaptable to follow the complex movement of the knee when incorporated in orthotic devices, having an upper and a lower extension overlying a central linking member and pivotally connected thereto wherein each extension moves in a relative angular motion determined by the coaction of a guide pin follower slidably and pivotally interacting with slots in the angular terminal portions of the extensions and the guide pin follower moving in a vertical slot in the central member; with provision for motion limiting stops.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates in general to a fluid delivery system and, more particularly, to a fluid delivery system provided within a golf bag.
2. Description of the Prior Art
It is well known in the art to provide mobile fluid delivery systems such as sport bottles and canteens. It is also known in the art to provide fluid pouches which may either be carried or strapped to a user's back for delivery of a fluid during exercise or other outdoor activities. One drawback associated with such devices is that they typically must be carried by the user during use. An additional drawback is that the delivery systems typically do not provide a useful mechanism for delivering fluid to a plurality of users. Therefore, it would be desirable to provide a portable fluid delivery system which need not be carried by a user, and which provides for delivery of fluid to a plurality of users.
It is also known in the art to provide kegs and the like for delivery of fluid to a large number of users. One drawback associated with such systems is even the small kegs and “party balls” are unwieldy and difficult to use in association with sports such as golf. It would, therefore, be desirable to provide a portable fluid delivery system which delivers fluid to a plurality of users, but is capable of being transported within a golf bag.
The difficulties encountered in the prior art discussed hereinabove are substantially eliminated by the present invention.
SUMMARY OF THE INVENTION
In an advantage provided by this invention, a golf bag is provided with a portable fluid delivery system.
Advantageously, this invention provides a golf bag with a fluid delivery system with a capacity of at least two and one-half liters.
Advantageously, this invention provides a golf bag with a fluid delivery system, and dispenser system with a plurality of cups.
Advantageously, this invention provides a golf bag with a fluid delivery system which conceals the fluid delivery system.
Advantageously, this invention provides a golf bag with a fluid delivery system which may be remotely actuated.
Advantageously, this invention provides a golf bag with a fluid delivery system which allows for pressurized fluid delivery.
Advantageously, this invention provides a golf bag with a fluid delivery system with means for insulating the fluid prior to delivery.
Advantageously, in the preferred example of this invention, a fluid delivery system is provided with a golf bag and means for retaining a plurality of golf clubs at least partially within the golf bag. A fluid container is also provided at least partially within the golf bag. The fluid container contains a fluid and means are provided for transferring the fluid from the fluid container to a fluid dispenser.
In the preferred embodiment of the invention, a remote control unit is coupled to a linear actuator to remotely actuate the dispenser to move from a position located within the golf bag to a position outside of the golf bag. Means are also provided for manually pumping pressurized air into the fluid container to allow the dispenser to obtain fluid from the system.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will now be described, by way of example, with reference to the accompanying drawings in which:
FIG. 1 illustrates a side elevation of the golf bag of the present invention;
FIG. 2 illustrates a side elevation in phantom of the golf bag of FIG. 1 ;
FIG. 3 illustrates a perspective cutaway view of the lower interior of the golf bag of FIG. 1 ;
FIG. 4 illustrates a side elevation in partial cutaway of the lower portion of the golf bag of FIG. 1 ;
FIG. 5 illustrates a side perspective view of an ejector tube of the golf bag of the present invention;
FIG. 6 illustrates a side elevation of the ejector actuator of the present invention;
FIG. 7 illustrates a side elevation of the ejection cylinder and U-bolt assembly of the present invention;
FIG. 8 illustrates a perspective view of the fluid pumping and delivery system of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
A golf bag according to the present invention is shown generally as ( 10 ) in FIG. 1 . The golf bag ( 10 ) includes a strap ( 12 ), several zipper pockets ( 14 ) and a towel retainer ( 16 ), such as those known in the art. The golf bag ( 10 ) includes a body ( 18 ), having a top ( 20 ) and a bottom ( 22 ).
As shown in FIG. 2 , the top ( 20 ) is provided with a plurality of ejector tubes ( 24 ) and a plurality of stationary tubes ( 26 ), sized to accommodate a golf club ( 28 ). The stationary tubes ( 26 ) are similar to those known in the art and are preferably constructed of an impact resistant plastic. Although only six ejector tubes ( 24 ) are shown with seven stationary tubes ( 26 ), any desired ratio of ejector tubes ( 24 ) and stationary tubes ( 26 ) may be utilized.
As shown in FIG. 3 , the ejector tubes ( 24 ) are provided along the interior face ( 30 ) of the body ( 28 ) of the golf bag ( 10 ). The interior face ( 30 ) is preferably constructed of a high-impact plastic, which is covered with a pliable vinyl covering ( 32 ). The vinyl covering may be colored, detailed or provided with text or logos as desired. ( FIGS. 1 and 3 ).
As shown in FIG. 3 , the stationary tubes ( 26 ) are secured to the interior face ( 30 ) of the golf bag ( 28 ) with small clips ( 34 ) and the stationary tubes ( 26 ) rest on a high-density plastic platform ( 36 ) which, in turn, tests on a support wall ( 37 ). The support wall ( 37 ) is secured to a larger high-density plastic platform ( 39 ) secured to the bottom ( 22 ) of the golf bag ( 10 ). The platform ( 36 ) is secured to the interior face ( 30 ) of the golf bag ( 10 ) by bolts or similar securement means known in the art. As shown, the platform ( 36 ) is constructed of dimensions which allow the ejector tubes to extend past the platform ( 36 ). ( FIGS. 1 and 3 ). As the ejector tubes ( 24 ) are substantially similar in construction, the description will be limited to a single ejector tube ( 24 ).
As shown in FIG. 5 , the ejector tube ( 24 ) is a hollow steel tube ( 38 ) approximately eighty-nine centimeters long, having an interior diameter of approximately 3.2 centimeters. The tube ( 38 ) is provided with a first slot ( 40 ) and a second slot ( 42 ), running from approximately one centimeter from the bottom ( 44 ) of the tube ( 38 ) for a length of about forty centimeters and a width of about one centimeter.
As shown in FIG. 6 , coupled to the bottom ( 44 ) of the tube ( 38 ) is an electronic trigger assembly ( 46 ). The trigger assembly ( 46 ) includes a steel bottom plate ( 48 ) and a steel side plate ( 50 ), welded to one another and to the bottom ( 44 ) of the tube ( 38 ). Welded or otherwise secured to the side plate ( 50 ) is a pull-type solenoid ( 52 ) provided with a shaft ( 54 ) such as those well known in the art. The shaft ( 54 ) is provided with a slot ( 56 ) into which is provided a steel linkage ( 58 ). The shaft ( 54 ) is also provided with a pair of holes ( 60 ) to accommodate a bolt ( 62 ), which passes through a hole (not shown) in the linkage ( 58 ). The bolt ( 62 ) is secured to the shaft ( 54 ) by a nut ( 64 ).
The linkage ( 58 ) is pivotally coupled to a secondary steel linkage ( 66 ) by a bolt ( 68 ). The secondary steel linkage ( 66 ) is coupled to a bracket ( 70 ) by a bolt ( 72 ). The bracket ( 70 ) is preferably constructed of steel and welded or otherwise secured to the bottom plate ( 48 ) of the electronic trigger assembly ( 46 ). The secondary steel linkage ( 66 ) is pivotally coupled to the trigger bar ( 74 ) of a standard, single rotor latch ( 76 ) by a bolt ( 78 ). As shown in FIG. 5 , the tube ( 38 ) is provided with a slot ( 80 ), preferably one and one-third centimeters wide and running five centimeters from the bottom ( 44 ) of the tube ( 38 ). As shown in FIG. 6 , the latch ( 76 ) is provided partially within the slot ( 80 ) to a point where the catch ( 84 ) is positioned preferably centrally within the tube ( 38 ). The latch ( 76 ) is preferably of a spring-loaded variety, which locks in response to a bar being pressed into contact with the catch ( 84 ) sufficiently to rotate the catch ( 84 ) to a substantially horizontal position. The catch ( 84 ) remains locked in position by the latch ( 76 ) until the top of the trigger bar ( 74 ) is rotated in a clockwise direction, thereby causing the spring-actuated latch ( 76 ) to release the catch ( 84 ).
As shown in FIG. 5 , rubber surgical tubing ( 86 ) is coupled to the tube ( 38 ) by an eyelet ( 88 ), which, in turn, is clamped to the tubing ( 86 ). The opposite end of the tubing ( 86 ) is secured to an eyelet fastener ( 90 ) by compression of the neck of the eyelet fastener around the tubing ( 86 ), or similar securement means. The rubber surgical tubing ( 86 ) is preferably of a length, diameter, resilience and construction sufficient to motivate a golf club to a speed of preferably at least one meter per second, more preferably, at least three meters per second and most preferably between four meters per second and ten meters per second.
As shown in FIG. 7 , a solid PVC cylinder ( 92 ) is provided with a height of approximately 3.175 centimeters and a diameter of approximately 3.175 centimeters. The cylinder ( 92 ) is also provided with a hole ( 94 ) through which is provided a steel U-bolt ( 96 ). The U-bolt ( 96 ) is provided with a threaded leg ( 98 ) and an unthreaded leg ( 100 ), with a connection bar ( 102 ) separating the central axes of the legs ( 98 ) and ( 100 ) by a distance of two centimeters.
As shown in FIG. 5 , the cylinder ( 92 ) is provided into the tube ( 38 ), whereafter the threaded leg ( 98 ) of the U-bolt ( 96 ) is provided through the hole ( 94 ). The unthreaded leg ( 100 ) extends through the slot ( 40 ), with the connection bar ( 102 ) being maintained within the slot ( 42 ). The eyelet fastener ( 90 ) is provided over the threaded leg ( 98 ) and secured thereto by a nut ( 104 ) in a manner such that the ends of both the legs ( 98 ) and ( 100 ) extend through the slot ( 40 ), and the connection bar ( 102 ) slides within the slot ( 42 ), to guide the cylinder ( 92 ) and prevent the cylinder ( 92 ) from becoming bound within the tube ( 38 ) during the actuation described below. The unthreaded leg ( 100 ) is preferably mounted to be received within the catch ( 84 ) and actuate the latch ( 76 ) to retain the catch ( 84 ) upon depression of the cylinder ( 92 ) through the tube ( 38 ) by a golf club ( 28 ). ( FIGS. 1 and 4 ).
As shown in FIG. 3 , all of the solenoids ( 52 ) are wired via six standard twelve-volt relays ( 105 ) to a central processing unit ( 106 ) which, in turn, is integrated with a radio frequency receiver ( 108 ) and antenna ( 109 ). ( FIGS. 3 and 4 ). The central processing unit ( 106 ) is electronically coupled to a battery ( 110 ) which, in the preferred embodiment, is a rechargeable sealed lead acid battery, such as those known in the art. ( FIGS. 1 and 3 ). In the preferred embodiment, the battery ( 110 ) is a PS-12180, 12-volt, 18 AMP hour battery manufactured by Power Sonic of Redwood City, Calif. As shown in FIG. 1 , to install the battery ( 110 ) in the golf bag ( 10 ), a door ( 112 ) hingably coupled to the bottom ( 22 ) of the golf bag ( 10 ) is opened from its releasable closure to reveal a battery compartment ( 114 ) located within the bottom ( 22 ) of the golf bag ( 10 ).
In the preferred embodiment, the bottom ( 22 ) is constructed of a heavier, more abrasion resistant plastic material than the interior face ( 30 ), to provide the golf bag ( 10 ) with rigidity, increased abrasion resistance and protection of the battery compartment ( 114 ) from external forces, and from forces associated with unintentional shifting of the battery ( 110 ) within the compartment ( 114 ). Also, the bottom ( 22 ) of the golf bag ( 10 ) is preferably constructed with a diameter less than about forty centimeters in diameter, and more preferably, approximately thirty centimeters in diameter, to allow the golf bag ( 10 ) to be retained by conventional golf bag retention mechanisms, such as golf carts (not shown) and the like.
Once the battery ( 110 ) has been inserted into the battery compartment ( 114 ), the door ( 112 ) may be releasably latched as is known in the art to prevent inadvertent removal of the battery ( 110 ) from the battery compartment ( 114 ). As shown in FIG. 3 , also electrically coupled to the central processing unit ( 106 ) by standard twelve-volt relays ( 115 ) is a linear actuator ( 116 ) which, in the preferred embodiment is a twelve-volt linear actuator with a retracted length of 41.3 centimeters, and a stroke length of 30 centimeters. ( FIGS. 4 and 8 ). Although the linear actuator ( 116 ) may be of any suitable size, dimension or load, in the preferred embodiment the linear actuator ( 116 ) is a Model 6178E linear actuator manufactured by AEI Components of Cerritos, Calif., having a static load capacity of five hundred pounds, a load capacity of one hundred pounds, a speed of 1.3 centimeters per second, and a built in limit switch. As shown in FIG. 3 , the linear actuator ( 116 ) is bolted or otherwise secured to interior face ( 30 ) of the golf bag ( 10 ).
As shown in FIG. 8 , the shaft ( 118 ) of the linear actuator ( 116 ) is coupled to a steel bracket ( 120 ), having a vertical rear arm ( 122 ) and a lateral right-angle side arm ( 124 ). The side arm ( 124 ) is preferably provided with an upwardly extending steel post ( 126 ), extending into and secured to a cup form ( 128 ). Although the cup form ( 128 ) may be constructed of any suitable dimensions or material, in the preferred embodiment, the cup form ( 128 ) is preferably constructed of a Styrofoam interior ( 130 ), adhesively secured to a standard plastic cup ( 132 ), such as those desired to be utilized for drinking in association with the present invention. Adhesively secured to the Styrofoam ( 130 ), the cup ( 132 ) provides a mount upon which additional standard cups ( 134 ) may be releasably stacked for storage and later use. ( FIGS. 2 and 7 ).
The vertical rear arm ( 122 ) is coupled to a tap ( 136 ) by a hose clamp ( 138 ) or similar means. Although the tap ( 136 ) may be of any type known in the art, in the preferred embodiment, the tap ( 136 ) preferably extends a sufficient distance above the steel bracket ( 120 ) to allow a cup ( 134 ) to be inserted between the outlet ( 140 ) of the tap ( 136 ) and the steel bracket ( 120 ). The handle ( 142 ) is preferably of a novelty design associated with golf, such as a golf ball or the like. The tap ( 136 ) is coupled to plastic tubing by a standard tubing connector ( 146 ), such as that known in the art.
As shown in FIG. 8 , the tubing ( 144 ) is coupled to a fluid container ( 148 ) which, in the preferred embodiment is a two and one-half gallon square high-density Polyethylene carboy of food grade quality. The fluid container ( 148 ) is preferably friction fit with a resilient, insulative sleeve ( 150 ) constructed of any desired insulative material. The fluid container ( 148 ) is preferably provided with a screw-on cap ( 152 ) in fluid communication with a one-way valve ( 154 ) having a predetermined release pressure below that of the pressure containment specifications associated with the fluid container ( 148 ). Coupled to the one-way valve ( 154 ) is an additional length of tubing ( 156 ) coupled to a manual air pump ( 158 ), such as those known in the art.
Like the linear actuator ( 116 ), the pump ( 158 ) is secured to the interior face ( 30 ) of the golf bag ( 10 ). ( FIG. 2 ). The pump ( 158 ) is preferably secured at a height where the handle ( 160 ) of the pump ( 158 ) is even with the top ( 20 ) of the golf bag ( 10 ) when the handle ( 160 ) is in the lowered position. Preferably, the handle ( 160 ) is provided with a novelty top ( 162 ), such as a golf ball or the like. As shown in FIG. 2 , the top ( 20 ) of the golf bag ( 10 ) is provided with an opening ( 164 ) slightly larger than the top ( 162 ) of the handle ( 160 ), and which provides sufficient clearance for a user's finger (not shown) to extend through the opening ( 164 ), grab the handle ( 160 ) and lift the handle for pumping.
As shown in FIG. 8 , the tubing ( 144 ) coupled to the tap ( 136 ) connects to the container ( 148 ) via a fluid coupling ( 166 ), such as those known in the art. On the interior of the fluid container ( 148 ), the coupling ( 166 ) is in fluid communication with a hose ( 168 ) which extends to the lower-most portion of the container ( 148 ). Once the fluid container ( 148 ) has been provided with a fluid ( 176 ) such as beer or the like, the sleeve ( 10 ) is stretched around the fluid container ( 148 ) and the tubing ( 144 ) and ( 156 ) is coupled to the fluid container ( 148 ). Thereafter, the fluid container ( 148 ) is provided into the golf bag ( 10 ) through a zippered door ( 178 ) which, thereafter, is zipped shut. ( FIGS. 2 and 7 ).
As shown in FIG. 2 , also secured to the interior face ( 30 ) of the golf bag ( 10 ) by a steel bracket ( 180 ) is a twelve-volt stereo receiver ( 182 ), such as those well known for use in association with vehicles and the like. In the preferred embodiment, the receiver is provided with an AM/FM tuner, a television receiver, a combination compact disc and DVD player, and is also electrically coupled to a video monitor ( 184 ), such as those associated with vehicles and the like. Preferably, the stereo receiver ( 182 ) and video monitor ( 184 ) are covered with a protective zippered face ( 186 ), which may be unzipped to reveal the video monitor ( 184 ) and the control elements associated with the stereo receiver ( 182 ). Preferably, the compact disc/DVD player ( 188 ) component of the stereo receiver ( 182 ) is positioned to allow the insertion of compact discs and DVD's ( 190 ) laterally into the stereo receiver ( 182 ).
As shown in FIG. 4 , the battery ( 110 ) is also coupled to a connection jack ( 170 ) provided in the bottom ( 22 ) of the golf bag ( 10 ). When it is desired to charge the battery ( 110 ), a standard twelve-volt battery charger ( 172 ) is coupled to a power source ( 174 ) and coupled to the connection jack ( 170 ). Once the battery ( 110 ) has been charged, the battery charger ( 172 ) can be disconnected from the golf bag ( 10 ).
As shown in FIG. 1 , the golf bag ( 10 ) is provided with a web strap ( 192 ) on one side, and a web strap ( 194 ) on the other side, terminating in a cam buckle ( 196 ), similar to those associated in the prior art with straps attached to golf carts for the attachment of golf clubs thereto. Due to the oversized nature of the golf bag ( 10 ), many prior art web straps associated with golf carts and the like may not be sufficiently long to encompass the golf bag ( 10 ). Accordingly, a web strap ( 198 ) associated with a golf cart (not shown) may be coupled to the cam buckle ( 196 ) associated with the golf bag ( 10 ), and a cam buckle ( 200 ) associated with a golf bag (not shown), may be coupled to the web strap ( 192 ) associated with the golf bag ( 10 ).
When it is desired to utilize the golf bag ( 10 ) of the present invention, the battery ( 110 ) is charged and inserted into the battery compartment ( 114 ) of the golf bag ( 10 ). The fluid container ( 148 ) is filled with a fluid and inserted into the golf bag ( 10 ) through the zippered door ( 178 ). Golf clubs ( 28 ) are then inserted into the ejector tubes ( 24 ) with sufficient force to engage the catches ( 84 ) and actuate the latches ( 76 ) against the pressure of the tubing ( 86 ). The remaining golf clubs ( 28 ) may thereafter be inserted into the stationary tubes ( 26 ). The golf bag ( 10 ) may thereafter be coupled to a golf cart (not shown), utilizing the web straps ( 192 ) and ( 194 ), and cam buckle ( 196 ), to couple the golf bag ( 10 ) to the web strap ( 198 ) and cam buckle ( 200 ) associated with the golf cart (not shown).
When it is desired to obtain a golf club ( 28 ) associated with one of the ejector tubes ( 24 ), a radio frequency remote control unit ( 202 ), such as those known in the art, is utilized. As shown in FIG. 1 , the remote control unit ( 202 ) is provided with a plurality of buttons ( 204 ), ( 206 ), ( 208 ), ( 210 ), ( 212 ) and ( 214 ), associated with individual ejector tubes ( 24 ). As shown, the location of the buttons ( 204 ), ( 206 ), ( 208 ), ( 210 ), ( 212 ) and ( 214 ) are representative of the location of the ejector tubes ( 24 ) on the golf bag ( 10 ). When it is desired to obtain a desired golf club ( 28 ), the associated button ( 206 ) is depressed on the remote control ( 202 ). The radio frequency transmission associated with depression of the button ( 206 ) is received by the radio frequency receiver ( 108 ) located within the golf bag ( 10 ), which the central processing unit ( 106 ) translates into actuation of the associated ejector tube ( 24 ). ( FIGS. 1 and 3 ). The central processing unit ( 106 ) thereafter sends an electronic signal to the solenoid ( 52 ) associated with the desired ejector tube ( 24 ). Upon receipt of the electronic impulse, the solenoid ( 52 ) causes the shaft ( 54 ) to retract, thereby causing the linkage ( 58 ) to move upward and pivot the secondary steel linkage ( 66 ) clockwise. ( FIG. 6 ). As the secondary steel linkage ( 66 ) is pivotally coupled to the trigger bar ( 74 ), the trigger bar ( 74 ) also pivots clockwise, thereby causing the spring loaded catch ( 84 ) to release the unthreaded leg ( 100 ) of the U-bolt ( 96 ). ( FIGS. 4 , 5 and 6 ). Once released, the tubing ( 86 ) retracts, thereby drawing the attached threaded leg ( 98 ), and the cylinder ( 92 ) coupled thereto, rapidly upward through the tube ( 38 ). As the cylinder ( 92 ) moves upward through the tube ( 38 ), the cylinder ( 92 ) presses against the golf club ( 28 ), forcing it upward and out of the tube ( 38 ), whereafter a player (not shown) may grab the golf club ( 28 ) out of the air. In the preferred embodiment, the tubing ( 86 ) is sufficiently resilient so as to propel the golf club ( 28 ) completely clear of the tube ( 38 ) and golf bag ( 10 ). After the user is finished with the golf club ( 28 ), the golf club ( 28 ) may simply be reinserted into the tube ( 38 ) sufficiently to cause the unthreaded leg ( 100 ) to contact the catch ( 84 ) and cause the latch ( 76 ) to retain the unthreaded leg ( 100 ) until actuated again as noted above.
When it is desired to obtain a beverage from the golf bag ( 10 ), the button ( 216 ) associated with the linear actuator ( 116 ) is depressed, thereby sending a radio frequency signal from the remote control ( 202 ) to the radio frequency receiver ( 108 ). ( FIGS. 1 and 3 ). The central processing unit ( 106 ) being coupled to the radio frequency receiver ( 108 ) translates the receipt of the signal into actuation of the linear actuator ( 116 ). The handle ( 142 ) of the tap ( 136 ) contacts a spring loaded plastic door ( 218 ) pivotally coupled to the top ( 20 ) of the golf bag ( 10 ) over an opening ( 220 ), sufficiently large to allow the cups ( 134 ) and tap ( 136 ) to extend upward therethrough to reveal the handle ( 142 ) and cups ( 134 ). ( FIGS. 2 and 7 ).
Thereafter, a user may reach into the opening ( 164 ) in the top ( 20 ) of the golf bag ( 10 ) to pull the top ( 162 ) of the handle ( 160 ) upward, and thereafter begin pumping the handle ( 160 ) to sufficiently pressurize the fluid container ( 148 ). Once sufficient pressure has been obtained, a cup ( 134 ) may be removed from the cup form ( 128 ) and positioned below the tap ( 136 ). Thereafter, the handle ( 142 ) of the tap ( 136 ) may be pivoted to begin dispensing fluid ( 176 ) into the cup ( 134 ). Once a sufficient amount of fluid ( 176 ) has been dispensed, the handle ( 142 ) is tilted into its starting position. When no additional fluid ( 176 ) is required, a second button ( 217 ) associated with the linear actuator ( 116 ) is depressed, thereby causing the central processing unit ( 106 ) to cause the linear actuator ( 116 ) to retract the cup form ( 128 ) and tap ( 136 ) back into the golf bag ( 10 ). The spring loaded door ( 218 ) then closes as the cup form ( 128 ) and tap ( 136 ) retract into the golf bag ( 10 ), the door ( 218 ), and thereby leaving no indication of the presence of the cup form ( 128 ) or tap ( 136 ) within the golf bag ( 10 ). The handle ( 160 ) of the pump ( 158 ) may be thereafter pushed downward so that the only portion of the pump ( 158 ) visible from the top of the bag is the novelty handle ( 160 ), viewable through the opening ( 164 ).
When it is desired to utilize the stereo receiver ( 182 ), the zippered door ( 178 ) of the golf bag ( 10 ) is opened, and a separate remote control ( 222 ) associated with the stereo receiver is actuated to operate the stereo receiver ( 182 ) and video monitor ( 184 ). ( FIGS. 1 and 2 ). If a DVD ( 190 ) is inserted into the stereo receiver ( 182 ), the DVD ( 190 ) will begin playing and displaying a video image ( 224 ) on the video monitor ( 184 ). When use of the stereo receiver ( 182 ) is no longer desired, the remote control ( 222 ) is again actuated to turn off the stereo receiver ( 182 ) and video monitor ( 184 ). Thereafter, the zippered door ( 178 ) may be closed over the stereo receiver ( 182 ) and video monitor ( 184 ) to protect it from the elements.
Although the invention has been described with respect to a preferred embodiment thereof, it is also to be understood it is not to be so limited, since changes and modifications can be made therein which are within the full, intended scope of this invention as defined by the appended claims.
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A dispenser is located within a golf bag and remotely controlled and coupled to a linear actuator, which extends the fluid dispenser outside of the golf bag upon actuation of the remote control. The remote control can also be actuated to cause the fluid dispenser to retract into the golf bag to hide the fluid delivery system from view.
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BACKGROUND OF THE INVENTION
[0001] The present invention relates to a device for examining nerve function, and more specifically, to a device for examining nerve function which examines a sensation in the hands or the feet of a subject such as a patient having diabetes or spinal nerve damage, so as to check a disease condition, to prevent an accident, and to treat the disease.
[0002] In general, diabetes is a disease in which cells are unable to absorb sugars entered into the body and the blood sugar level increases, either because an enough amount of insulin that the body requires is not produced, or because the produced insulin does not work properly in the cells.
[0003] The diabetes may lead to serious complications, for example complications in large blood vessels or small blood vessels developed from hardening of the arteries in blood vessels. This may cause renal failure and require long-term hemodialysis, or cause a coronary or cerebrovascular disorder or retinal damage, and even cause necrosis of the foot due to blood supply shortage.
[0004] Especially, when a neurological complication is developed and the peripheral nerve function declines in the nervous system which connects nerves from the head through the body to the hands and the feet, sensation becomes dulled. Even though stones or sand come into the shoes, it is hard to feel this. In such a case, there was a problem that the symptoms were more exacerbated by a secondary bacterial infection when the wound is caused on the foot during activity. The neurological complication, of course, may occur in the hand because the nervous system is connected to the hand. But, it is more common to occur in the foot rather than in the hand.
[0005] The hypoesthesia first occurs in the feet in which blood circulation is not performed smoothly. Unless properly treating or preventing this, small blood vessels in the toes would be blocked and as a result the situation that the toes get rotten may occur.
[0006] This finally may cause a serious situation that the above-knee amputation should be performed when a necrosis area starting from the toes gradually spreads out above the knees. In this case, a diabetic patient would have worse blood circulation and this will lead to not only a serious complication, but also even death.
[0007] Therefore, it is very important for diabetic patients to check the hypoesthesia symptom in advance for proper treatment and prevention of wounds. In the conventional arts, in order to examine the hypoesthesia symptom of the diabetic patients, doctors just pricked the patient's feet with a needle-shaped mono filament, or vibrated a “U”-shaped tuning fork and brought it into contact with the patient's toe or sole. However, these methods have the following problems: the examination result depending on an inspector is unreliable; since the patient's sensation condition is determined through empirical methods that are not standardized and not expressed in numbers, the examination is not relatively accurate; and it is unable to systematically check how much the patient's hypoesthesia has progressed, a specific area of the hypoesthesia, etc.
[0008] In the meanwhile, because paresthesia also happens to patients with spinal nerves damaged due to a spine disease or a spine accident and they show the same symptoms as discussed above, the similar examination is conducted for them like diabetic patients. Therefore, it is very important for those patients to exactly pinpoint the damaged area of nerves and the degree of the damage for selecting a proper treatment method such as emergency surgery.
SUMMARY OF THE INVENTION
[0009] In order to solve the above-mentioned problems, an object of the present invention is to provide a device for examining nerve function capable of: greatly improving accuracy and reliability of the examination using a standardized stimulator and a standardized stimulator fixing member; expressing as a number the degree of hypoesthesia or the status of hypoesthesia through the examination for the patient's nerve function; exactly determining the specific position of the patients' hypoesthesia so as to systematically and actively determine a diagnosis and treatment course for the patients having hypoesthesia for example those suffering diabetes; and especially detecting the state of blood circulation to check the position of hypoesthesia.
[0010] Further, another object of the present invention is to provide a device for examining nerve function capable of: accurately adjusting the degree of stimulation by automatically moving a pressurizer having an actuator; and recording and checking the degree of hypoesthesia in real time and for a long period of time with a subject wearing an elastic clothing, stimulation gloves or stimulation boots in practical life.
[0011] In particular, another object of the present invention is to provide a device for examining nerve function capable of: checking if a subject can feel pain caused by applying pressure, and if a subject can distinguish positions among multiple pressure points (positions of pressure points), and if a subject can detect vibration, if a subject can detect change in temperature, and if a subject can distinguish difference in the applied pressure, through the pain caused by the applied pressure; and checking the state of blood circulation through oxygen saturation or temperature of the hypoesthesia area. In addition, the present invention aims to provide a device for examining nerve function capable of not only proceeding with the process of measuring the above-mentioned capabilities step by step but also reviewing the measured capabilities and the state of blood circulation in an audio or video message or in a printed material.
[0012] In order to achieve the above-described objects, the device for examining nerve function according to the present invention includes at least one stimulator for stimulating the human body to examine nerve function in the human body; and a stimulator fixing member formed in the shape corresponding to the hands or the feet of the human body, in which the stimulator is located at one side of the stimulator fixing member so as to fix the hands or the feet of the human body.
[0013] The stimulator may include at least one of a pressurizer for pressurizing the skin to provide stimulation and a vibrator for applying vibration-type stimulation to the skin.
[0014] The pressurizer may include a hollow holder fixed at one side of the stimulator fixing member; and a stimulating pin inserted into a hollow which is formed inside the hollow holder and moving forward and backward in the hollow, in which the front end portion is moved to pressurize the skin to provide stimulation, and the back end portion may include a pressing unit or an actuator.
[0015] The pressurizer may further include a raised portion formed on the stimulating pin to move together with the stimulating pin; and a stopper formed in the hollow, in which the raised portion is blocked by the stopper.
[0016] Unlike this, the stimulator may include a hollow holder fixed at one side of the stimulator fixing member and having multiple hollows; and at least one stimulating pin inserted into a hollow that is formed inside the hollow holder and moving forward and backward in the hollow, in which the front end portion is moved to pressurize the skin to provide stimulation and the back end portion may include a pressing unit or an actuator.
[0017] The stimulator may further include a holder fixing member for rotatably fixing the hollow holder to the simulator fixing member.
[0018] The holder fixing member is integrally fixed to the simulator fixing member and may include a fixing ring having an inner circumferential surface so as to allow the hollow holder to be fitted to the fixing ring.
[0019] The stimulator may include a toe moving member for moving the position of the toe to stimulate the toe.
[0020] The toe moving member may include a lift for lifting the toe of the feet; and an elevator for elevating the lift.
[0021] The stimulator may include an electric heater for applying heat to the skin to stimulate the skin.
[0022] The present invention may further include at least one blood circulation detecting sensor placed on the stimulator fixing member for detecting blood circulation of the human body.
[0023] The blood circulation detecting sensor may include at least one of an oxygen saturation sensor for measuring oxygen saturation in the blood inside the skin and a temperature measuring sensor for measuring skin temperature.
[0024] The simulator fixing member may include an elastic clothing that is wearable on the hands or feet of the human body.
[0025] The simulator fixing member may include a fixing frame corresponding to the hands or feet of the human body.
[0026] The fixing frame may include a supporting plate for supporting the hands or feet of the human body; and a first extendable rod extending to the upward direction of the supporting plate, in which the stimulator is integrally fixed to the first extendable rod.
[0027] The fixing frame may include a supporting plate for supporting the hands or feet of the human body; a first extendable rod extending to the upward direction of the supporting plate; a second extendable rod extending to the different direction from the first extendable rod and having the stimulator at the front end portion; and a joint for fixing the second extendable rod to the first extendable rod.
[0028] The simulator fixing member may further include a stimulator movement rail for guiding the path of movement of the stimulator.
[0029] The stimulator movement rail may have a rail groove corresponding to a protrusion formed on one side of the stimulator.
[0030] In the meanwhile, the present invention includes: a stimulator for stimulating the human body to examine nerve function of the human body, having at least one of a pressurizer for pressurizing the skin to provide stimulation, a vibrator for applying vibration-type stimulation to the skin, a toe moving member for moving the position of the toe to stimulate the toe, and an electric heater for applying heat to the skin to stimulate the skin; a stimulator fixing member formed in the shape corresponding to the hands or feet of the human body, in which the stimulator is located at one side so as to fix the stimulator to the hands or feet of the human body; a blood circulation detecting sensor for detecting blood circulation of the human body, placed on the stimulator fixing member and having at least one of an oxygen saturation sensor for measuring oxygen saturation in the blood inside the skin and a temperature measuring sensor for measuring skin temperature; a confirmation button operated by a subject to produce a confirmation signal which confirms that the skin or the toe has been stimulated by the stimulator; a terminal for setting a sequential measurement process by comparing a pre-set stepwise measurement process based on a confirmation signal produced by the confirmation button and a measurement value measured in the blood circulation detecting sensor, or for converting the confirmation signal or the measurement value into printable data; a guiding unit for guiding the sequential measurement process set in the terminal in an audio or video message; and a printer connected to the guiding unit through the terminal 51 so as to communicate with each other for printing out data converted in the terminal.
[0031] According the present invention, because nerve function is examined by checking if sensation is detected by the stimulator, the device for examining nerve function has the following effects: significantly improving precision and reliability of examinations for nerve function; and systemically and actively determining an exact diagnosis for patients having hypoesthesia with the symptoms of diabetes or spinal nerve damage; also exactly diagnosing the area of chronic neurological complications, and accurately adjusting the degree of stimulation; and recording and checking the degree of hypoesthesia in real time and for a long period of time with a subject wearing an elastic clothing, stimulation gloves or stimulation boots in practical life.
[0032] In particular, a systematic and scientific examination is possible because the device is capable of: checking if a subject can feel pain caused by applying pressure, and if a subject can distinguish positions between two pressure points (positions of two areas), and if a subject can detect vibration, if a subject can detect change in temperature, and if a subject can distinguish difference in the applied pressure, through the pain caused by the applied pressure; and checking the degree of hypoesthesia by screening the state of blood circulation through oxygen saturation or temperature of the hypoesthesia area. In addition, because the device is capable of not only guiding the stepwise process of measuring the capabilities by voice or display, it is possible to not only perform examinations with ease, but also to see the measured capabilities and the state of blood circulation in an audio or video message, or in a printed material so as to understand the degree of hypoesthesia with ease.
BRIEF DESCRIPTION OF DRAWINGS
[0033] FIG. 1 is a cross-sectional view illustrating a device for examining nerve function according to the first embodiment of the present invention.
[0034] FIG. 2 is a cross-sectional view illustrating an example of the pressurizer illustrated in FIG. 1 .
[0035] FIG. 3 is a cross-sectional view illustrating an example of the vibrator illustrated in FIG. 1 .
[0036] FIG. 4 is a cross-sectional view illustrating an example of the movement rail illustrated in FIG. 1 .
[0037] FIG. 5 is a cross-sectional view illustrating a device for examining nerve function according to the second embodiment of the present invention.
[0038] FIG. 6 is a cross-sectional view illustrating a first extendable rod, a second extendable rod and a joint of FIG. 5 .
[0039] FIG. 7 is a cross-sectional view illustrating a device for examining nerve function according to the third embodiment of the present invention.
[0040] FIG. 8 is a cross-sectional view illustrating a device for examining nerve function according to the fourth embodiment of the present invention.
[0041] FIG. 9 is a cross-sectional view illustrating a device for examining nerve function according to the fifth embodiment of the present invention.
[0042] FIG. 10 is a cross-sectional view illustrating a device for examining nerve function according to the sixth embodiment of the present invention.
[0043] FIG. 11 is a cross-sectional view illustrating a device for examining nerve function according to the seventh embodiment of the present invention.
[0044] FIG. 12 is a cross-sectional view illustrating a device for examining nerve function according to the eighth embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0045] Hereinafter, the device for examining nerve function according to preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.
[0046] First, the device for examining nerve function according to the first embodiment of the present invention may include a stimulator 10 and a stimulator fixing member 20 , as shown in FIGS. 1 to 4 .
[0047] The stimulator 10 , which generates stimulation on the human body in order to examine nerve function of the human body, includes a pressurizer 11 for pressurizing the skin with a stick-type stimulating pin 112 as shown in FIG. 2 and/or a vibrator 12 for applying vibration to the skin that comes into contact with a vibration surface 112 with a vibration motor 121 as shown in FIG. 3 .
[0048] The pressurizer 11 may include a hollow holder 111 and a stimulating pin 112 as shown in FIG. 2 .
[0049] The hollow holder 111 is fixed at one side of an elastic clothing 21 , which is a kind of stimulator fixing member 20 , and multiple hollow holders may be provided, for example at an important stimulation point such as a meridian point, at a main check point representing a long distance from the heart, or at a position representing a certain distance from the toes.
[0050] The stimulating pin 112 may be made of wood or of a monofilament of plastic material or nylon material. Such a stimulating pin 112 is inserted into a hollow 111 a that is formed inside the hollow holder 111 in such a manner so as to be movable forward and backward.
[0051] The stimulating pin 112 may has a blunt front end portion, but it is rather preferable to form an actuate stimulation point 112 a . Also, the back end portion may preferably include a pressing unit 112 b or an actuator 13 for enabling forward and backward movement of the stimulating pin 112 in a selective manner. Such an actuator 13 can be configured to adjust the movement distance of the stimulating pin 112 which moves forward and backward depending on the magnitude of supplied voltage.
[0052] According to the present invention, inspectors may therefore check an accurate response from the subject's response when considering the numerical stimulation that is expressed in a certain distance from the toes of the subject, i.e. the length of forward movement of the stimulating pin 112 that is moved forward by the actuator 113 . As a result, the device is capable of automatically and numerically measuring how much the symptoms of hypoesthesia have improved or deteriorated. Especially, in the case that the movement distance of the stimulating pin 112 is adjusted by the actuator 113 , it is able to adjust the strength of the contact of the stimulating pin 112 , thereby precisely checking the sensory reaction from the subject.
[0053] Meanwhile, the stimulating pin 112 described above may be connected to a sensor for detecting the movement distance when moving forward and backward, which is not illustrated. It is preferable that such a sensor is placed in the hollow holder 111 and may include a normal optical sensor or hall sensor. Those skilled in the art could easily understand the configuration of such a sensor, and thus its detailed description will be omitted.
[0054] On the other the hand, multiple pressurizers 11 may be provided with one adjacent to another and with one separated from another. These pressurizers 11 individually pressurize the skin in a state where they are separated from one another. In other words, the pressurizers 11 individually pressurize two areas at the same time. Therefore, the subject may check whether to distinguish two stimulation points at which the stimulation occurs. That is, if the subject is unable to distinguish two stimulation points, it may be determined that the sensation has been reduced at the areas corresponding to the stimulation points.
[0055] In the pressurizers 11 , a raised portion 112 c may be formed on the stimulating pin 112 so as to prevent the stimulating pin 112 that moves inside the hollow holder 111 from moving away from the hollow holder 111 as shown in FIG. 2 , and a stopper 111 b may be formed in the hollow 111 a . That is, the raised portion 112 c is blocked by the stopper 111 b and thereby restricting the forward/backward distance of the stimulating pin 112 .
[0056] Here, the hollow holder 111 described above, as illustrated, may be integrally fixed to the stimulator fixing member 20 via a movement rail 40 , which will be described below. In other words, the hollow holder 111 may be indirectly fixed to the stimulator fixing member 20 . Such a hollow holder 111 may be fixed to the movement rail 40 in a detachable manner by bolting, and it may also be permanently fixed to the movement rail 40 by welding or bonding.
[0057] Otherwise, the hollow holder 111 may be directly fixed to the stimulator fixing member 20 . In this case, the hollow holder 111 is directly connected to the stimulator fixing member by bolting or bonding. In such a case that the stimulator fixing member 20 is the elastic clothing 21 described above, the hollow holder 111 may be fixed to the elastic clothing 21 by bonding, or fixed to the elastic clothing 21 by bolting using an bracket, which is not illustrated. Of course, the vibrator described above is fixed to the stimulator fixing member 20 , the movement rail 40 or the elastic clothing 21 in the same way as the hollow holder 111 . Those skilled in the art could easily carry out the method of fixing such a hollow holder 111 and a vibrator 12 , and thus its detailed description will be omitted
[0058] As shown in FIG. 1 , the stimulator fixing member 20 may include multiple pressurizers 11 and multiple vibrators 12 at one side to fix the stimulator 10 to the hands 1 or the feet 2 of the human body, and it is formed in the shape corresponding to the feet 2 of the human body, and it may also include the elastic clothing 21 which is wearable on the feet 2 .
[0059] In general, the elastic clothing 21 may include either a socks-type item of clothing or a stocking-type item of clothing, as shown in FIG. 1 .
[0060] Accordingly, when using the device for examining nerve function according to the present invention, the subject may move in a state where the subject is wearing the elastic clothing 21 and at the same time check the degree of hypoesthesia by receiving various types of stimulation such as pressure or vibration.
[0061] In the meantime, the device for examining nerve function according to the present invention may further include a blood circulation detecting sensor 30 for detecting blood circulation of the human body, which is placed on the stimulator fixing member 20 .
[0062] The blood circulation detecting sensor 30 , which is a sensor for detecting blood circulation of the human body, may include an oxygen saturation sensor 31 for measuring oxygen saturation in the blood inside the skin and/or a temperature measuring sensor 32 for measuring skin temperature, as shown in FIG. 1 .
[0063] Accordingly, when using the device for examining nerve function according to the present invention, the subject may move in a state where the subject is wearing the elastic clothing 21 and at the same time check the patient's nerve function by measuring oxygen saturation in the blood circulating in the feet or feet temperature.
[0064] In the meanwhile, it is also possible to provide a stimulator movement rail 40 on the stimulator fixing member 20 for guiding the path of movement of the stimulator 10 so as to reduce the number of pressurizers 11 or vibrators 12 arranged on the feet of the subject and to provide stimulation to one point or to some points continuously, as shown in FIG. 4 .
[0065] Here, the stimulator movement rail 40 has a rail groove 41 formed to correspond to a protrusion 13 that is formed on one side of the pressurizer 11 or the vibrator 12 as shown in FIG. 4 , so that the pressurizer 11 or the vibrator 12 could apply stimulation to specific points or to a specific point or to some points continuously moving along the rail groove 41 .
[0066] As shown in FIG. 7 , the stimulator movement rail 40 may be provided on sensitive boots 23 , which will be described below, and in this case, a scaled ruler 224 may be placed at one side so as to measure the movement distance, height, etc. of the stimulator 10 .
[0067] As shown in FIGS. 5 and 6 , the device for examining nerve function according to the second embodiment of the present invention may include a fixing frame 22 corresponding to the feet 2 of the human body, as a kind of stimulator fixing member 20 .
[0068] The fixing frame 22 includes a supporting plate 220 , a first extendable rod 221 , a second extendable rod 222 and a joint 223 , as shown in FIG. 5 .
[0069] The supporting plate 220 supports the feet 2 of the human body. When the subject puts the feet on the supporting plate 220 , the oxygen saturation sensor 31 and the temperature measuring sensor 32 placed on the supporting plate 220 may check blood condition of the patient's feet. The oxygen saturation sensor 31 and the temperature measuring sensor 32 of the supporting plate 220 may also be placed at the first extendable rod 221 so that they may operate above the supporting plate 220 , as marked in a broken line in the figure. That is, the oxygen saturation sensor 31 and the temperature measuring sensor 32 may be either placed on the first extendable rod 221 so as to measure the upper portion of the feet 2 , or placed on the supporting plate 220 so as to measure the bottom surface of the feet 2 .
[0070] The first extendable rod 221 is placed in such a manner as to extend above the supporting plate 220 , as shown in FIG. 5 . If there are scale marks 224 for measuring the height of the pressurizer 11 or the vibrator 12 , the measurement position will be expressed in a number.
[0071] In addition, the first extendable rod 221 is hinge-connected to a hinge shaft 225 placed on the supporting plate 220 . Before the subject puts the feet on the supporting plate 220 , the first extendable rod 221 remains splayed out. When the subject puts the feet on the supporting plate 220 , however, the first extendable rod 221 stands up to the direction of the feet, resulting in easier sensation examination.
[0072] The second extendable rod 222 is placed in such a manner as to extend to the different direction from the first extendable rod 221 , in which the pressurizer 11 or the vibrator is placed at the front end portion of the second extendable rod. At this time, it is preferable that the second extendable rod 222 is placed in such a manner as to extend to the perpendicular direction with regard to the first extendable rod 221 . Here, it is possible not to provide the second extendable rod 222 when the pressurizer 11 or the vibrator 12 is placed on the first extendable rod 221 . In other words, the pressurizer 11 or the vibrator 12 may be placed on the first extendable rod 221 . The pressurizer 11 or the vibrator 12 may be embedded into the supporting plate 220 .
[0073] The joint 223 fixes the second extendable rod 222 to the first extendable rod 221 . Here, the joint 223 , which fixes the first extendable rod 221 and the second extendable rod 222 to each other using a fixing unit such as a clamping screw 226 , may freely adjust the horizontal position and vertical position of the stimulator 10 , as shown in FIG. 6 .
[0074] As shown in FIG. 7 , the device for examining nerve function according to the third embodiment of the present invention may include sensitive boots 23 which are wearable on the feet 2 of the human body, as a kind of stimulator fixing member 20 .
[0075] The sensitive boots 23 may include a pressurizer 11 , a vibrator 12 , an oxygen saturation sensor 31 and a temperature measuring sensor 32 , all of which were described above.
[0076] Further, the sensitive boots 23 may include a data storage unit 100 for storing measurement values measured in the oxygen saturation sensor 31 and temperature measuring sensor 32 , so that the subject can measure changes in oxygen saturation and temperature of the feet 2 in practical life for a long period of time, and a battery 200 for supplying power to the stimulator 10 and the data storage unit 100 .
[0077] Accordingly, the subject can record and check the degree of hypoesthesia in real time and for a long period of time, wearing the sensitive boots 23 in practical life.
[0078] As shown in FIG. 8 , the device for examining nerve function according to the fourth embodiment of the present invention may include sensitive gloves 24 which are wearable on the hands 1 of the human body, as a kind of stimulator fixing member 20 .
[0079] The sensitive gloves 24 may include a pressurizer 11 , a vibrator 12 , an oxygen saturation sensor 31 and a temperature measuring sensor 32 , all of which were described above.
[0080] Further, the sensitive gloves 24 may include a data storage unit 100 for storing measurement values measured in the oxygen saturation sensor 31 and temperature measuring sensor 32 , so that the subject can measure changes in oxygen saturation and temperature of the hands 1 in practical life for a long period of time, and a battery 200 for supplying power to the stimulator 10 and the data storage unit 100 .
[0081] Accordingly, the subject can record and check the degree of hypoesthesia in real time and for a long period of time, wearing the sensitive gloves 24 in practical life.
[0082] As shown in FIG. 9 , the device for examining nerve function according to the fifth embodiment of the present invention has the same configuration as the device according to the first embodiment, except that there is an only difference from the first embodiment in that the stimulator includes an electric heater 19 . This electric heater 19 generates heat with an internal electric coil (not illustrated) to stimulate the skin through the heat by applying the heat of the electric coil to the skin. Therefore, the subject may detect the stimulation by the heat and check the area of hypoesthesia. That is, the subject may determine that the sensation is not reduced on the area where the electric heater 19 is located if the subject feels the heat from the electric heater 19 . Otherwise, it may be determined that the sensation has been reduced.
[0083] The electric heater 19 may be placed on the stimulator fixing member 20 together with the pressurizer 11 and the vibrator 12 described above, but it may also be placed on the stimulator fixing member 20 alone. When the electric heater 19 is arranged in the above-described movement rail 40 illustrated in FIG. 4 , it may move along the movement rail 40 .
[0084] The configuration of the electric heater 19 could easily be not only understood but also embodied by those skilled in the art, and thus its detailed description will be omitted.
[0085] As shown in FIG. 10 , the device for examining nerve function according to the sixth embodiment of the present invention is different from the device according to the embodiment described above only in that the stimulator includes a toe moving member 15 . The toe moving member 15 elevates the toe to move the position of the toe.
[0086] The toe moving member 15 , for example, may include a lift 15 a for lifting the toe and an elevator for elevating the lift 15 a , as illustrated.
[0087] The lift 15 a may be formed either in the shape of the plate so as to support a lower portion of the toe as illustrated, or in a cylinder so as to allow the toe to be inserted.
[0088] The elevator may include a rotating motor 15 d , a pivot shaft 15 c which is pivotally rotated by the rotating motor 15 d on the supporting plate, and an elevation nut 15 b that is screw-connected to the pivot shaft 15 c to be elevated and connected to the lift 15 a . In other words, the toe moving member 15 may include a lift 15 a , a rotating motor 15 d , a pivot shaft 15 c and an elevation nut 15 b.
[0089] The pivot shaft 15 c is pivotally rotated by the rotating motor 15 d to elevate the lift 15 a along with the elevation nut 15 b , thereby moving the position of the toe. As a result, the subject may check the area of the toe where the sensation is reduced through the stimulation to the toe produced by the movement of the position. That is, the subject may determine that the sensation of the examined toe is not reduced if the subject detects the stimulation by the movement of the position. Otherwise, it may be determined that the sensation of the examined toe has been reduced.
[0090] As shown in FIG. 11 , the device for examining nerve function according to the seventh embodiment of the present invention is configured in a different manner from the above-described ones in the pressurizer 11 . Such a pressurizer 11 , for example, may include a hollow holder 111 ′ fixed to the stimulator fixing member 20 described above through the movement rail 40 and having multiple hollows 111 a , and at least one stimulating pin 112 inserted into a hollow 111 a that is formed inside the hollow holder 111 ′ and moves forward and backward in the hollow, in which the front end portion is moved to pressurize the skin to provide stimulation and the back end portion comprises a pressing unit 112 b or an actuator 113 , as illustrated. At this time, the hollow holder 111 ′ is fixed at one end of the movement rail 40 to be connected to the stimulator fixing member 20 described above.
[0091] Here, the pressurizer 11 described above may further include a holder fixing member for rotatably fixing the hollow holder 111 ′ to the movement rail 40 on the stimulator fixing member 20 described above. The holder fixing member, for example, is integrally connected to the movement rail 40 on the stimulator fixing member 20 described above, and may include a fixing ring having an inner circumferential surface so as to allow the hollow holder to be fitted to the fixing ring. In other words, the hollow holder 111 ′ is mounted into the fixing ring 114 to be fixed to the movement rail 40 , thereby being rotatably fixed to the movement rail 40 .
[0092] The fixing ring 114 may be fixed to the movement rail 40 in a detachable manner by bolting, or permanently fixed to the movement rail 40 by welding or bonding. Such a fixing ring 114 preferably has an end portion which is formed in such a manner as to be bent inwards as illustrated. Therefore, the bent end portion allows the fixing ring 114 to rotatably bind the hollow holder 111 ′.
[0093] Meanwhile, the stimulating pins 112 comes in various thickness and each is inserted into one of multiple hollows 111 a . That is, the stimulating pins 112 include multiple pins which are different from each other in thickness. Therefore, only one of the stimulating pins 112 comes out of the hollow holder 111 ′ to stimulate the skin as needed. When the hollow holder 111 ′ rotates in the same way as the revolver in the gun, the stimulating pins 112 come out one by one based on their thickness to stimulate the skin. In other words, the inspector may examine the subject's skin in various ways.
[0094] On the other the hand, in the case that the stimulation fixing member 20 includes the above-described fixing frame 22 illustrated in FIG. 5 , the hollow holder 111 ′ or the fixing ring 114 described above is placed on the fixing frame 22 . Of course, the hollow holder 111 ′ or the fixing ring 114 is fixed to the first extendable rod 221 or the second extendable rod 222 of the fixing frame 22 . At this time, the hollow holder 111 ′ or the fixing ring 114 is preferably fixed to the first extendable rod 221 or the second extendable rod 222 via the joint 223 described above.
[0095] Also, the device for examining nerve function according to the first to sixth embodiments of the present invention described above may be configured to examine a patient in a state where the patient is lying. This could be easily understood by those skilled in the art, and thus its detailed description will be omitted.
[0096] As shown in FIG. 12 , the device for examining nerve function according to the eighth embodiment of the present includes a stimulator 10 , a stimulator fixing member 20 , a blood circulation detecting sensor 30 , a confirmation button 59 , a terminal 51 , a printer 57 , and a guiding unit.
[0097] The stimulator 10 includes at least one of a pressurizer 11 , a vibrator 14 , a toe moving member 15 , and an electric heater 19 , all of which were described above. And the stimulator fixing member 20 includes an elastic clothing 21 or a fixing frame 22 , both of which were described above. Further, the blood circulation detecting sensor 30 includes an oxygen saturation sensor 31 and/or a temperature measuring sensor 32 , both of which were described above. In addition, the terminal 51 may include a common personal computer (PC). Also, the guiding unit may include, for example, a monitor 52 or a speaker 55 as illustrated.
[0098] The confirmation button 59 is connected to the terminal 51 . When the subject operates the confirmation button, the resultant confirmation signal is transmitted to the terminal 51 .
[0099] In the device for examining nerve function according to the eighth embodiment of the present invention, a confirmation signal is transmitted to the terminal 51 by the confirmation button 59 when either the skin or the toe is stimulated by the stimulator 10 and the subject operates the confirmation button 59 , and the measurement value that is measured in the blood circulation detecting sensor 30 is also transmitted to the terminal 51 . Therefore, the terminal 51 sets a sequential measurement process by comparing the pre-set stepwise measurement process based on the confirmation signal produced by operating the confirmation button and the measurement value measured in the blood circulation detecting sensor 30 , or converts the confirmation signal or the measurement value into printable data. The terminal 51 sets the sequential measurement process through an installed drive program. Also, the terminal 51 is capable of storing the printable data in a file, transmitting the data online, or storing the data on a storage medium in a CD type. In addition, the terminal may inform the patient's condition, based on the confirmation signal produced by the confirmation button, through a guiding unit. This could be easily understood or embodied by those skilled in the art, and thus its detailed description will be omitted.
[0100] Here, the pre-set stepwise measurement process described above refers to the order of the stepwise operation of the stimulator 10 . That is, the stepwise measurement process is a process of performing many different types of examinations in order using the multiple types of stimulators 10 including a pressurizer 11 , a vibrator 14 , a toe moving member 15 , and an electric heater 19 . In more detail, the stepwise measurement process may include the following steps in order: pressurizing the skin with the pressurizer 10 ; and then vibrating the skin with the vibrator 14 ; and thereafter stimulating the toe with the two moving member 15 , and finally stimulating the skin with the electric heater 19 .
[0101] In the meanwhile, the terminal 51 guides the stepwise measurement process in a video or audio message via a monitor 52 or a speaker 55 . Once the stimulation by the pressurizer 11 is complete, the terminal 51 informs via a monitor 52 or a speaker 55 that another examination will be carried out by the vibrator 14 . At this time, the terminal 51 is confirmed that the stimulation by the pressurizer 11 has been complete through a confirmation signal produced by the confirmation button 59 . And then, the terminal 51 informs via a monitor 52 or a speaker 55 that another examination will be carried out by the toe moving member 15 once it is confirmed by the confirmation button 59 that the stimulation by the vibrator 14 has been complete. The terminal 51 guides patients in such a way until the final examination by the electric heater 19 is complete.
[0102] The printer 57 may be connected to the guiding unit through the terminal 51 so as to communicate with each other. The printer 57 prints out the data converted in the terminal 51 . Accordingly, the inspector may see the subject's examination results at a single look.
[0103] The present invention is not limited to the above-described embodiments, and various modifications and changes can be made by those skilled in the art without departing from the spirit and scope of the present invention. It is therefore intended that the claims cover all such modifications and other changes encompassed by the accompanying claims, not by the description.
[0104] The device for examining nerve function according to the present invention can check if the sensation is detected by a stimulator to examine nerve function, and it is therefore capable of greatly improving accuracy and reliability of examinations for nerve function.
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The present invention relates to a device for examining nerve function. In order to examine the function of a nerve of the human body, the device for examining nerve function of the present invention includes: at least one stimulator for stimulating the human body; and a stimulator-fixing member having a form corresponding to the hands or feet of the human body, wherein the stimulator is located at one side of the simulator-fixing member so as to fix the stimulator to the hands or feet of the human body. The device for examining nerve function of the present invention further includes at least one blood-circulation detection sensor fixed at the stimulator-fixing member. According to the present invention, since the degree of hypoesthesia is examined through the stimulation of the stimulator, test accuracy and reliability may be greatly improved and it is possible to systematically and actively determine a diagnosis and course of treatment for a patient having diabetes or spinal nerve damage, e.g. hypoesthesia.
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RELATED APPLICATIONS
[0001] This application is the U.S. National Phase under 35 U.S.C. §371 of International Application No. PCT/CA2009/000785, filed on Jun. 4, 2009, which in turn claims the benefit of U.S. Provisional Application No. 61/058,805, filed on Jun. 4, 2008, the disclosures of which Applications are incorporated by reference herein.
FIELD OF THE INVENTION
[0002] The present invention generally relates to packaging systems. More particularly, the present invention relates to a deaeration system for flexible packages and a method associated thereto.
BACKGROUND OF THE INVENTION
[0003] Several different types of products are packaged typically in flexible packages. After filling of the packages, in order to reduce the overall volume of the package; it is often desired to remove air remaining within the package before sealing thereof. Removing the air from the packages before closing them results in a flat and straight flap (upper part of the package above the product). Then, it is possible for the closing system belts to be closer to the product. Therefore, it is possible to reduce the distance between the product and the sealed or sewn joint. By reducing this distance, the freeboard (distance between the upper part of the package and the product level when the package is full) is also reduced. The required length of empty bags is consequently reduced, which result in packing material savings (economic and ecological savings).
[0004] The invention described in U.S. Pat. No. 7,316,102 involves an apparatus for extracting air from within flexible packages. The package is displaced along a conveyor system and has air removed therefrom under a hood which is linked to a subsequent closing mechanism.
[0005] However, flexible packaging customers still have several requirements that are not completely satisfied with existing deaeration systems, including:
Reducing a warehouse bursting packages problem; Reducing the amount of air in packages; Maintaining current productivity, reliability and quality; Using the smallest footprint possible (ex.: providing 7 feet maximum length available for the footprint); Providing flexible package sizes (from 13″ to 20″); and Using less freeboard.
[0012] Consequently, there is still presently a need for a deaeration system and associated method which offers superior results in terms of the efficiency of the removal of air from the flexible package and addresses the above requirements.
SUMMARY OF THE INVENTION
[0013] The present invention addresses at least one of the above-mentioned needs.
[0014] More particularly, the present invention provides a system for removal of air from an interior of a flexible package before closure thereof, the system comprising:
a lower conveyor sub-system for continuously displacing the package along a length of the system; an upper driving sub-system holding continuously an upper part of the package, keeping the upper part closed along a length of its displacement, said upper driving sub-system comprising at least one perforated belt bag-opening sub-system comprising:
at least one pair of adjacent guiding structures, each guiding structure having a profile surface facing a corresponding profile surface of the opposite guiding structure; a plurality of driving belts, each belt circulating around a corresponding guiding structure of the at least one pair of guiding structures, each of said belts following a path along the corresponding profile of the guiding structure on which the driving belt is travelling; a pulley system for driving displacement of the plurality of driving belts around the guiding structures; and a belt sub-system vacuum source applying vacuum behind the belts, said at least one bag-opening sub-system spreading partially open the upper part of the package at a specific location along the length of the system when passing between the profile surfaces of adjacent guiding structures, said upper driving sub-system being synchronized with the lower conveyor sub-system;
and
a deaeration port located above the bag-opening sub-system allowing removal of air from the interior of the package when the package is positioned under the port.
[0023] Preferably, the lower conveyor sub-system has a profile or shape that allows the package to increase in height sufficiently to remove vertical tension from the top of the package.
[0024] Preferably, the bag-opening sub-system has a shape that allows the upper part of the package to be partially opened by a vacuum source connected to bag-opening sub-system.
[0025] Preferably, the air removal section displaces the package through a perforated belt system or any other equivalent system allowing repositioning of the package and allowing passage of a certain quantity of air.
[0026] Preferably, the air removal section opens a portion (in the upper part) of the package. In this section, the upper sides of the package are maintained against the driving belts to spread it out, partially opening the package. In fact, a source of vacuum applied behind the perforated belts, a pulley desynchronisation and a curved block or guiding structure constrain the two belts to follow a curved path (opposite of one another).
[0027] The present invention also provides a method for removing air from the interior of flexible packages before closure thereof, comprising the following steps:
a) providing a system for removal of air comprising:
a lower conveyor sub-system for continuously displacing the package along a length of the system; an upper driving sub-system holding continuously an upper part of the package, keeping the upper part closed along a length of its displacement, said upper driving sub-system comprising at least one perforated belt bag-opening sub-system comprising:
at least one pair of adjacent guiding structures, each guiding structure having a profile surface facing a corresponding profile surface of the opposite guiding structure; a plurality of driving belts, each belt circulating around a corresponding guiding structure of the at least one pair of guiding structures, each of said belts following a path along the corresponding profile of the guiding structure on which the driving belt is travelling; a pulley system for driving displacement of the plurality of driving belts around the guiding structures; a belt sub-system vacuum source applying vacuum behind the belts, said at least one bag-opening sub-system spreading partially open the upper part of the package at a specific location along the length of the system when passing between the profile surfaces of adjacent guiding structures, said upper driving sub-system being synchronized with the lower conveyor sub-system;
and
a deaeration port located above the bag-opening sub-system allowing removal of air from the interior of the package when the package is positioned under the port,
b) displacing continuously the package along a horizontal direction, using the low conveyor sub-system; c) maintaining continuously an upper part of the package closed along a length of its displacement, using the upper driving sub-system; d) partially opening the upper part of the package at a specific location along the length of the system, using said bag-opening sub-system; and e) removing air from the interior of the package when the package is positioned, at said specific location, using the deaeration port.
[0041] According to the present invention, there is also provided a system for removing air from an interior of a flexible package before closure thereof, comprising:
displacement means for continuously displacing the package along a horizontal direction while supporting a bottom of the package and holding an upper part of the package at all times; raising means for raising the bottom of the package along a distance of travel of the package to reduce vertical tension within the package; and opening means for opening a portion of the upper part of the package, said opening means comprising:
at least one pair of guiding structures, each guiding structure having a profile surface facing a corresponding profile surface of the opposite guiding structure; a plurality of driving belts, each belt circulating around a corresponding guiding structure of the at least one pair of guiding structures, each of said belts following a path along the corresponding profile of the guiding structure on which the driving belt is travelling; a pulley system for driving displacement of the plurality of driving belts around the guiding structures; and a belt sub-system vacuum source applying vacuum behind the belts, said bag-opening sub-system spreading partially open the upper part of the package at a specific location along the length of the system when passing between the profile surfaces of adjacent guiding structures, while maintaining displacement of the package;
and
a deaeration port located above the opening means allowing removal of air from the interior of the package when the package is positioned under the port.
[0051] The system according to the present invention offers the following advantages:
Capability of staying in control of the top of package Keeping current packaging machine configuration Capability of being added at the exit of machine Capability to remove air “in-line” (continuously) with up to 150 fpm linear speed Keeping high level of reliability Preventing air entrance into the package (after air extraction and prior to sealing) Package shape conditioning after sealing
[0059] A non-restrictive description of preferred embodiments of the invention will now be given with reference to the appended drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0060] FIG. 1 is a side view of the system according to a preferred embodiment of the present invention;
[0061] FIG. 2 is another side view of the system shown in FIG. 1 with the packages removed and the upper housing installed;
[0062] FIG. 3 is another side view of the system shown in FIG. 2 with the upper housing removed;
[0063] FIG. 4 is a another side view of the system according to a preferred embodiment of the present invention;
[0064] FIG. 5 is a side close-up view of the upper driving system shown in FIG. 4 ;
[0065] FIGS. 6A and 6B are top and side-cut views respectively of an aluminium block or guiding structure and associated hardware from FIG. 4 ;
[0066] FIG. 7 is a detailed side view of the upper driving system (air removal section) shown in FIG. 5 ;
[0067] FIG. 8 is another side close-up view of the upper driving system shown in FIG. 4 ;
[0068] FIG. 9 is a side view of the system shown in FIG. 4 , during its operation with packages, illustrating different work stations;
[0069] FIG. 10 is a top view of part of the upper driving system shown in FIG. 4 ;
[0070] FIGS. 11 a and 11 b are front views of the interaction of a package with a system according to another preferred embodiment of the present invention, showing lower and upper positions of the package;
[0071] FIGS. 12 a to 12 c are side views of the interaction of a package with a system according to another preferred embodiment of the present invention, as the package travels along the conveyor system;
[0072] FIGS. 13 a and 13 b are perspective views of the interaction of a package with the system shown in FIG. 11 , before and after removal of air;
[0073] FIGS. 14 a to 14 d are perspective views of the interaction of a package with the system shown in FIG. 11 , illustrating air extraction, vacuum shutdown and maintaining of the condition of the package after extraction.
[0074] FIGS. 15A to 15C are side, top and front views respectively of the system shown in FIG. 1 with the upper housing and associated support structure installed.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0075] As shown in FIGS. 1 to 3 and 15 A to 15 C, a deaeration system 10 for flexible packages 12 according to the present invention is shown. The system comprises a lower conveyor sub-system 14 . The system 10 also has an upper driving system 16 maintaining continuously the upper part of the package 12 closed along a significant length of its displacement. The upper driving system 16 comprises one or several bag-opening sub-systems, preferably connected to a vacuum source 18 , that allows opening of the flexible package at a specific location when the package travels along the upper driving system 16 and on the lower conveyor system 14 . The system also comprises a deaeration port 20 located above the upper driving system 16 connected to the vacuum source 18 that allows removal of air from the interior of the package 12 when the package is positioned under the deaeration port 20 by the upper driving system 16 and the lower conveyor system 14 , under the bag-opening sub-system.
[0076] In the present application, it is to be understood that the deaeration port can be an aspiration port, a dedusting port, a vacuum port, a system connected to a vacuum source or any other equivalent system known to the person of skill in the art which is capable of removing air or substances from the package.
[0077] As better shown in FIG. 4 , the lower conveyor 14 includes a steel frame 30 , conveyor rollers 32 and a conveyor belt 34 . The conveyor belt is driven by a motor 36 at a constant linear velocity in order to displace the package towards the closing or sealing systems located downstream. The steel frame has a shape 38 that allows the conveyor belt and the package to rise along a certain height while translating along the system.
[0078] As better shown in FIG. 5 , the system 40 controlling the upper part of the package has three sections, 42 , 44 , 46 . The first 42 and third 46 sections are made of aluminum blocks or guiding structures, pulleys and belts. The upper part of the package is maintained closed through pressure exerted by the belts on the package. The belts are driven by a motor 48 at the same linear velocity as the lower conveyor belt.
[0079] As better shown in FIGS. 6A and 6B and 7 , the mid-section of the system 44 includes aluminum blocks or guiding structures 50 having a special shape, perforated belts 52 , pulleys 54 and various other pieces of hardware. On each side of the system, a tube 56 connected to a high debit ventilator removes the air through an opening in the aluminum blocks or guiding structures and through the perforated belt.
[0080] As better shown in FIG. 8 , the vacuum removal system 18 is a deaeration port 60 located above the upper section. This port is connected to a high flow ventilator 62 for removal of the air.
[0081] Explanation of the Operation of the System
[0082] The package arrives from the packaging system with a certain quantity of air inside thereof, in addition to the packaged product. The product reaches a certain height within the package. The upper part of the package which is not filled is designated as the freeboard. During removal of air from the package, the sides of the freeboard approach one to another. Raising the package using the shape of the bottom conveyor will result in loose freeboard. Once an amount of play (loose) is given to the freeboard, the package enters into the deaeration module. The blocks or guiding structures in the deaeration section have a special internal curvature. The belts are assembled in a manner such that there is a greater length on the side on which the belts face each other to follow the curvature. Moreover, the source of vacuum produced by the high flow ventilator which removes the air from behind the belts constrains the belts to follow the curvature of the block or guiding structure. Finally, as the belts are perforated, a certain quantity of air passes through them so that the upper sides of the package are constrained to follow the belt and curvature of the block or guiding structure.
[0083] In FIG. 9 , the package can be seen along three different stations along the system. The steps presented below are shown on the figure.
A. Module receives packages from packaging machine. B. Bottom of the package is raised prior to vacuum extraction. C. Top of package is forced to open and air is extracted from package. D. Package exits towards the sealer.
[0088] In FIG. 10 , the air removal section of the system is seen from above. The two blocks or guiding structures facing each other can be seen, as well as the package along three different positions during its displacement through the system. The package is represented through bold lines and the hash marks represent the opening through which air is removed from the inside of the package.
[0089] FIGS. 11 to 14 illustrate various aspects of the system during operation.
[0090] FIGS. 11 a and 11 b show lower and upper positions of the package along the conveyor illustrating how tension is removed from the top of the package once it is lifted.
[0091] FIGS. 12 a to 12 c are side views of the package as it travels along the conveyor system. In this example, the slope is 3 inches over 2 feet, preferably at 150 fpm.
[0092] FIGS. 13 a and 13 b illustrate the package before and after removal of air.
[0093] FIGS. 14 a to 14 d are perspective views of the interaction of a package with the system shown in FIG. 11 , illustrating air extraction, vacuum shutdown and maintenance of the condition of the package after extraction of air.
[0094] Preferably, the present invention offers the following performance parameters:
Linear speeds up to 150 fpm Adjustable to bag sizes (conveyor height) No additional freeboard required (to hold the package while filling it) Maximum footprint length of 7 feet Air removal time estimated at 0.4 second No air entrance into the package (after air extraction and prior to sealing)
[0101] According to the present invention, there is also provided a method removing air from an interior of a flexible package before closure thereof, comprising the following steps:
a) displacing the package along a horizontal direction; b) maintaining continuously an upper part of the package closed along a significant length of its displacement; c) partially opening the upper part of the package at a specific location along the length of the system; and d) removing air from the interior of the package when the package is positioned, at said specific location.
[0106] Preferably, the method further comprises the step of decreasing, along the length of the displacement, a distance between a means for displacing the package in step a) placed under the package and a means for maintaining the package closed in step b) to remove vertical tension from the upper part of the package.
[0107] A package, after going through the above-described deaeration system or method, can then be sealed or closed using any sealing or closing system known in the art.
[0108] Differences with Respect to the Prior Art
[0109] As described in U.S. Pat. No. 7,316,102, packages must go through the hood (see 1 st paragraph of the summary of the invention . . . “vacuum extraction hood through which the packages are conveyed”), whereas, in the present invention, the hood is replaced by a deaeration port and the package passes under the port.
[0110] As described in U.S. Pat. No. 7,316,102, the open package goes through the hood and it is gradually closed by the belts facing each other and located in the upper part. In the present invention, the package is closed when it arrives at the air removal section (the package is held by the upper driving system belts) and it is partially opened. In fact, a portion of it stays closed while it is still held by the belts. This partial opening is done while the package is moving forward.
[0111] With the system presented in U.S. Pat. 7,316,102, the upper part of the bag is not held before and during air extraction. On the contrary, in the present invention; the upper part of the package is continuously held, even during air extraction, ensuring an exact positioning of the upper part of the bag, thus ensuring a constant transfer to the closing system and an increase in the closing system reliability and quality of the finished product.
[0112] In the invention described in U.S. Pat. No. 7,316,102, the upper part of the package is not held before the end of air extraction; whereas in the present invention, the upper part of the bag is continuously held. The distance between the conveyor which supports the lower part of the package and the belts supporting the upper parts of the package is adjustable. Consequently, it is possible to control tensions exerted to the sides of the package when the air is extracted from it. Since the distance between the conveyor supporting the lower part of the package and the belts holding the upper part of the package is controlled, the condition (behaviour) of the flap is also controlled and the distance between the closing system and the product level into the bag is decreased which reduces the freeboard required.
[0113] In U.S. Pat. No. 7,316,102, air extraction is made through a big hood maintained at a negative pressure. Air is drawn up everywhere around several packages at the same time. Loss of efficiency is obvious and should be certainly quantifiable. In the present invention, air extraction is made through an aspiration port. The dimension of the air aspiration end is smaller than the upper part of the packages from which air is extracted. This small end, located very near the upper part of the package offers more efficiency (and increased performance).
[0114] Moreover, the system described in U.S. Pat. No. 7,316,102 has a voluminous hood that makes the system more burdensome, even cumbersome or bulky. The present invention has a small deaeration port allowing a realization of the same functions more efficiently while keeping the system dimension to its minimum.
[0115] Although the present invention has been explained hereinabove by way of preferred embodiments thereof, it should be pointed out that any modifications to these preferred embodiments within the scope of the appended claims are not deemed to alter or change the nature and scope of the present invention.
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System for allowing removal of air from the interior of flexible packages, in which material can be found, including a conveyor transporting and supporting the bottom of the flexible packages or package, a second sub-system holding the top part of the package and an air extraction system. The package is raised vertically while being displaced along the conveyor. Removing the air from the packages before closing them results in a flat and straight flap, while reducing the distance between the product and the sealed or sewn joint. The process is accomplished through a continuous displacement of the package. These advantages result in packing material savings. A method for allowing removal of air is also disclosed.
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This is a continuation of International patent application PCT/IL00/00353, designating the United States, having an international filing date of Jun. 16, 2000, and published in English under PCT Article 21(2) on Dec. 28, 2000, publication No. WO/0078421, which is hereby incorporated herein by reference in its entirety. The entire disclosure of the prior application, is considered as being part of the disclosure of the accompanying application, and is hereby incorporated by reference therein.
FIELD OF THE INVENTION
The present invention is generally in the field of computer games.
BACKGROUND OF THE INVENTION
Computer games gained considerable popularity as one of the major forms of entertainment, particularly for children and teenagers. Computer games are also increasingly used as an educational aid. In such games, a user has to perform a certain task within a virtual environment based on certain game-specific roles. For example, the user has to maneuver a figure through a maze, “destroy” the “bad guys”, overcome obstacles, etc., all of course within the virtual environment.
The user controls the game through a user interface which may be the keyboard or the “mouse” of the computer, or may be a game-dedicated interface such as a joystick, a pointer, etc.
In most computer games, the virtual environment is an imaginary environment generated by the computer, although some computer games make use of a virtual environment based on or derived from a real-life environment.
SUMMARY OF THE INVENTION
The present invention provides a novel computer game. In accordance with the present invention, the computer game involves a virtual environment comprising a virtual dental image, for example a virtual image of teeth of the individual playing the game (referred to herein at times as “user”). In the computer game of the invention, the user performs a task which is carried out in this virtual environment. Thus, for example, the user, typically a child, may perform a task of eliminating virtual infectious agents from the teeth, a task of translocating or reorienting the teeth in a manner corresponding somewhat to that in which teeth are translocated or reoriented in an orthodontic treatment, etc.
A game with a virtual environment based on an individual's own teeth, may be constructed from data captured of the individual's teeth prior to the onset of orthodontic treatment. Such a game may, for example, be provided to the user by the orthodontist who captured the virtual three-dimensional (3D) image of the user's teeth. The computer game may be recorded on a memory medium, e.g. a CD-ROM, a magnetic disk, etc.
In accordance with its first aspect the present invention provides a computer game which may be run in a computer and associated storage medium, in which a user, through a user interface, performs one or more tasks within a virtual environment, the game being characterized in that said environment is a virtual environment comprising a virtual three-dimensional dental image consisting of at least one tooth of the user; and said one or more tasks comprise improving a certain virtual condition associated with at least one tooth.
In accordance with another aspect the present invention provides a method for playing a game in a computer comprising:
(a) extracting data from a storage medium, the data being representative of a virtual environment comprising a virtual three-dimensional dental image consisting of at least one tooth, and displaying said virtual environment; (b) performing, in response to a user's command, one or more tasks within a virtual environment to obtain a modified environment and displaying same; said one or more tasks comprise improving a certain virtual condition associated with at least one tooth; and optionally (c) storing data representative of said modified environment in a storage medium.
By a still further aspect the invention provides a storage medium storing data being representative of a computer game capable of being run in a computer, in which a user, through a user interface, performs one or more tasks within a virtual environment; said virtual environment comprising a virtual three-dimensional dental image comprising of at least one tooth of the user; and said one or more tasks comprise improving a certain virtual condition associated with the at least one tooth.
By a still further aspect the invention provides a storage medium storing data being representative of a virtual environment generated by the above method.
In accordance with a preferred embodiment, the virtual environment is based on the user's own teeth and comprises a virtual image of at least one of the user's teeth.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a drawing which depicts a flowchart of the steps of a representative method for a user to play a game in a computer, in accord with one embodiment of the inventive subject matter.
FIG. 2 is a drawing which depicts a flowchart of the steps of a representative method for a user to play a game in a computer, in accord with one embodiment of the inventive subject matter.
FIG. 3 is a drawing which depicts a representative virtual three dimensional dental image, in accord with one embodiment of the inventive subject matter.
FIG. 4 is a drawing which depicts the following representative virtual dental tools, in accord with one embodiment of the inventive subject matter: toothbrush, tooth pick, dental floss, and gum massaging aid.
DETAILED DESCRIPTION OF THE INVENTION
In the following, the invention may at times be described with reference made to various physical entities, such as “tooth/teeth”, “jaw”, “bracket”, “wire”, “band”, etc. It should, however, be understood that it implies, in most cases, a virtual presentation of these entities in the virtual game environment. (At times, however, as may be realized from the context, these terms will refer to the real-life physical entities). Similarly, the terms “movement”, “reorientation”, “translocation”, etc., refer, in most cases, to acts carried out within the virtual environment.
In accordance with the present invention a computer game is provided wherein a user has to perform one or more tasks within a virtual environment. The characterizing feature of the invention is that the virtual environment comprises a virtual 3D dental image of teeth, preferably those of the user itself. The virtual image typically comprises a continuous section of the individual's teeth, preferably all teeth of one or both jaws of the individual. The task which the user has to perform is to improve a certain virtual condition which is associated with the teeth. The computer game is typically provided on a storage medium which may be a memory chip, a magnetic disk or diskette, a CD-ROM, etc. The game is played through a user's interface which may be the computer's keyboard, a mouse, a joystick, a dedicated game-specific interface, etc.
The computer game generates a virtual environment which comprises a 3D virtual teeth model, preferably including substantially all teeth of both jaws. The term “substantially” means to denote that while, typically the model will have all teeth of both jaws, at times some teeth, e.g. molar teeth, may not be included.
The user is typically an individual, e.g. a child, undergoing an orthodontic treatment and the virtual environment in such a case is generated from data on the 3-D structure of his dental arches acquired by the orthodontist before, during or after an orthodontic treatment.
A method of acquiring a three-dimensional teeth image is disclosed in PCT Application, Publication No. WO 97/03622. Briefly, in this PCT application a 3D teeth image is obtained from a 3D physical teeth model. The 3D physical teeth model may be a negative teeth model including a matrix with a plurality of cavities or recesses, each corresponding to a tooth; or may be a positive teeth model, that includes a matrix with a plurality of projections or bulges, each corresponding to a tooth. The 3D image is then acquired by removing a portion of the model in a controlled, step-wise manner, and in each step capturing an optical image of the model or of the removed portion. Each of the optical images is then digitized and the plurality of images are then compiled to obtain a 3D digital dental image. Methods and systems for acquiring a 3D dental image are also disclosed in DE-A1-3,810,455, DE-C-4,141,311, U.S. Pat. No. 4,935,635 and U.S. Pat. No. 5,237,988.
A method for obtaining a dental occlusion map which may also be applied to generate the virtual 3D dental image of the virtual environment of the computer game of the invention is disclosed in PCT Application WO 98/52,493. Briefly, in this PCT application, the distance between opposite regions on opposite teeth of the upper and lower jaws of the mouth are determined and then a correspondence between the determined distance and regions on a mapping surface is being set-up. This PCT application is also incorporated herein by reference. FIG. 3 shows a representative virtual 3D dental image as disclosed in PCT Application WO 98/52,493.
In the computer game of the invention the user has to perform one or more tasks of improving a certain virtual condition in the 3D virtual teeth image. Such condition may, in accordance with one embodiment, be a relative position or orientation of one or more teeth or a jaw which differs from an “ideal” position or orientation. An “ideal” position or orientation may be that corresponding to that which would be a desired position or orientation in a real-life orthodontic treatment. This may indeed be the position or orientation corresponding to that aimed to be achieved by the orthodontist. Thus, the virtual teeth may be shifted in position or orientation in a manner which resembles that in which the teeth are translocated or reoriented in the real-life orthodontic treatment.
Moving of teeth or jaws may be achieved by dragging a certain tooth within a permitted limit using a mouse, by pointing on a tooth or jaw to be moved and defining the type of movement or reorientation by the use of a keyboard, etc.
In addition, the user may be given virtual tools or components to perform such movement. Such virtual tools or components may, by one embodiment, be virtual orthodontic components corresponding to real-life orthodontic components. Such virtual orthodontic components may include virtual brackets, a virtual arch-wire, virtual rubber bands or tension springs, etc. In addition to being a source of amusement, performing this task in such a computer game will also be educational to the user on the process of orthodontic treatment he may be undergoing.
FIG. 1 shows an exemplary, yet not exclusive, game sequence for playing the game in accordance with one embodiment of the inventive subject matter. In step 1 , the user first selects brackets and in step 2 places the brackets at appropriate positions on the surface of selected teeth, which may be some or all teeth of one jaw. In most cases, brackets are placed on the buccal teeth's surface. In step 3 , the user selects an arch-wire from a library of such wires. The library may also include wires of different widths, different cross-sectional shapes and different geometries. In step 4 , the geometry of the selected wire is changed. For example the wire may be made to follow a torturous path in a vertical and/or a horizontal plane. In step 5 , the wire is associated with the teeth by fitting it into virtual grooves in the brackets placed on the teeth's surface. For example, similar to a real-life procedure, the wire may first be anchored to brackets fitted on the molar teeth and then to the other brackets (all of course in the virtual environment). The relative reorientation or translocation of the teeth and/or jaws resulting from such a game sequence is computed in step 6 based on predetermined rules for such translocation or reorientation in accordance with the virtual force or movement applied by the wires.
The final outcome is then displayed in step 7 . In step 8 , it is determined whether the outcome, namely the final achieved state, is a perfect or close to a perfect relative position or orientation of the teeth and/or jaws. If yes, the game goal has been achieved and the process terminates. If no, the user is prompted in step 9 to repeat this game sequence. If no, the process terminates. If yes, the process returns to step 2 . The user may receive a score based on how close the final result was to a perfect final state.
FIG. 2 shows an exemplary, yet not inclusive game sequence for playing the game in accordance with another embodiment of the invention, in which the task to be performed by the user is to maintain teeth hygiene. This may involve use of virtual tools, corresponding to such tools used in normal dental hygiene: toothbrush, tooth picks, dental floss, gum massaging aids, etc. In this embodiment, the game may, for example, have the object of fighting tooth or gum decay, damage or infection which may be caused by carries or other infectious agents. In step 10 , the user is presented with a library of tools and has to select a tool to treat a certain developing virtual condition, e.g. carries or a gum infection. In step 12 , the game rules determine a certain continuous progress of infection which if not properly “treated” by the user will cause decay of one or more teeth, gum infection, potential bleeding, loss of teeth, etc. In step 13 , the user may score points depending on his ability to choose the right tools to treat a particular condition or in avoiding a condition from developing. In step 14 , it is determined whether the condition of the teeth is satisfactory. If yes, the process terminates. If no, then in step 15 , the user is prompted whether he wishes to select another tool. If no, the process terminates. If yes, the process returns to step 10 . Here again, the game, in addition to being amusing and providing an insight of the user into his own teeth, may be educational, particularly for children, on teeth oral hygiene methods and on the importance of maintaining oral hygiene.
In accordance with another embodiment of the invention the game may involve use of a variety of virtual imaginary tools such as virtual guns, wands, etc. in order to fight infectious agents of the teeth or gums.
In accordance with one embodiment of the invention the user may be permitted to manipulate the virtual environment so as to rotate the virtual teeth model, may be provided with controls allowing him to open and close the jaw in a manner similar to that performed in real life, etc. A manner of manipulating a 3D virtual teeth model in a virtual environment is disclosed in PCT Application WO 98/53428, the contents of which is incorporated herein by reference.
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The present invention relates to a computer game, which, when operating on a computer enables a user, via a user's interface, to perform one or more tasks within a virtual environment, the virtual environment comprising a virtual three dimensional dental image of at least one tooth and the tasks performed by the user leading to the improvement of a certain virtual condition associated with said at least one tooth. The three dimensional dental image employed in the computer game is preferably based on or derived from a real life dental environment. The invention further relates to a storage medium for storing data representation of the above computer game and to a method of playing the computer game of the present invention using a computer.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to coil handling apparatus and, more particularly, to a self-braking and self-tensioning coil reel.
2. Description of the Prior Art
Unreeling operations of coiled materials are often necessary in industrial situations. Telephone central offices, for example, use wire for making cross-connections on the main distributing frame and for similar applications. Coils of wire are mounted on a reel and wire is removed from the reel by pulling on the wire and causing the reel to rotate and unwind the wire. In order to prevent wire overrun and consequent entanglement and wastage of wire, a brake is provided on the reel for stopping the rotation of the reel when the pulling force is removed from the wire.
One type of wire reel brake, shown in J. P. Starace U.S. Pat. No. 3,796,392, granted Mar. 12, 1974, utilizes a resilient braking disk mounted to apply a braking force on the inner surface of the reel flange by the flat surface of the disk. The brake arm and shoe assembly is pivotally mounted on a base and is held away from the reel flange by the tension on the wire caused by the removal force as the wire is unreeled. Removal of this tension force allows the rotation of the brake arm assembly to bring the face of the brake disk against the inner face of the reel flange. Subsequent rotation of the reel wedges the braking shoe into contact with the flange surface to stop the rotation. The frictional braking force with this arrangement is determined by the disk material and cannot be adjusted.
Coils of wire for use with wire reels come in various thicknesses and hence an adjustable reel is desired for receiving such coils. Moreover, as the wire is removed from the coil, the coil configuration becomes shorter along its axis of rotation. Looseness in the coil wire on the reel permits the portion of wire being unwound under tension to become embedded in and bind in these loose coils, thereby interfering with the unreeling operation.
An adjustable reel is shown in J. E. Moore U.S. Pat. No. 3,830,445, granted Aug. 20, 1974, in which the two flanges are threaded together on a coil spring. Manual threading of the flanges together permits adjustments for various widths of coils and permits manual width adjustments during unreeling to maintain lateral tension on the coil. The spring provides a resilient lateral tensioning force. Such a reel, however, requires manual adjustment at various times during the unreeling operation.
SUMMARY OF THE INVENTION
In accordance with the illustrative embodiment of the present invention, automatic braking and lateral tensioning are provided by a wire reel having two telescoping flanges threaded together and a self-locking cylindrical disk brake bearing on the rim of one flange. The tightness of the fit of the brake shoe on its shaft can be adjusted to change the braking force or slippage permitted between the braking material and the flange rim. The brake arm assembly is pivotally mounted so as to be held clear of the flange rim as long as tension is maintained on the wire. Release of this tension permits the brake shoe to come into contact with the flange rim and, by a wedging action, exert sufficient frictional force to bring the flange to a stop. The inertia of the other reel flange allows it to continue rotation due to centrifugal force and, in doing so, to move laterally toward the braked flange under the influence of the threads at its hub.
It can be seen that the wire reel of the present invention is not only self-braking, but is also self-tensioning due to the lateral movement of the unbraked flange. Since this movement can occur each time the reel is braked, the proper lateral tension is maintained on the coil at all times throughout the unreeeling operation. No manual adjustments are required. Coils can be inserted on the reel simply by turning the unbraked flange in such a direction as to unscrew this flange from the braked flange, separating the flanges, inserting the new coil, and turning the unbraked flange back onto the braked flange.
Although this invention has direct application in the wire coil reeling art, it is also applicable to other reeling operations such as sewing thread unreeling, weaving, wire stock unreeling, rope manufacturing and cable reeling. The size of the reel and the type of material on the reel do not affect the self-braking and self-tensioning capabilities.
BRIEF DESCRIPTION OF THE DRAWING
In the drawings:
FIG. 1 is a perspective view of a self-braking and self-tensioning reel assembly in accordance with the present invention;
FIG. 2 is a perspective view of a partial assembly of the reel of the present invention showing the details of the hub of the braked flange;
FIG. 3 is a perspective view of the unbraked flange showing the details of the hub of the unbraked flange; and
FIG. 4 is an enlarged cross-sectional view of the brake disk and brake disk shaft of the brake assembly shown in FIGS. 1 and 2.
DETAILED DESCRIPTION
FIG. 1 shows a wire reel 2 having a wire coil 4 wound thereon and rotatably mounted on a shaft 6 (shown in FIG. 2) affixed to a support arm 8. Support arm 8 is mounted to a base 10 having supporting feet 11 and 13, which may have a slip-resistant lower surface. Wire reel 2 includes two generally circular flanges 12 and 14 for preventing wire coil 4 from spilling from the edges of reel 2. The inner or opposing surfaces or faces of flanges 12 and 14 are generally planar, smooth surfaces. A brake 20 is utilized for arresting the rotation of reel 2 and thereby controlling the winding or unwinding of wire 4 on reel 2. As shown more clearly in FIG. 2, brake 20 comprises a base 22 adjustably mounted to base 10 and having a brake arm 24 pivotally mounted thereon by a pin or shaft 26. Arm 24 has a right angled portion including a ceramic-lined wire guide 28 therein. At the other end of arm 24 there is mounted a generally disk-shaped brake shoe 32 mounted on a shaft 33. Shoe 32 can comprise any of the well-known varieties of friction materials.
Brake 20 is mounted to shaft 26 substantially parallel to the shaft 6 of reel 2. Arm 24 is positioned between flanges 12 and 14 and the brake shoe 32 is generally aligned with the rim of flange 14. Wire guide 28 is located in a generally central position between flanges 12 and 14. The weight of arm 24 normally pivots arm 24 on shaft 26 so as to bring brake shoe 32 into contact with the rim of flange 14. As shown in FIG. 1, however, the wire from coil 4 is threaded through guideway 28 and, when tension is applied to wire 4 in either of the directions indicated by arrows 38 or 4l, a vertical component of that tension raises arm 24 and moves brake shoe 32 away from flange 14.
Wire being removed from reel 2 is fed through guide 28 to supply the vertical component which releases brake shoe 32. Thus, reel 2 is free to rotate and unwind wire coil 4 in response to tension on the wire. When the tension on wire 4 is removed, arm 24 rotates under its own weight on shaft 26 until the periphery of brake shoe 32 establishes contact with the rim of flange 14. Subsequent rotation of reel 2 forces the brake disk 32 to be wedged into a braking contact with the rim of flange 14 and thereby applies a relatively large braking force to the reel. When a tension or removal force is reapplied to wire 4, arm 24 is again pivoted upward to remove brake disk 32 from braking contact with the rim of flange 14. This permits reel 2 freedom to rotate.
If reel 2 is rotated in the opposite or rewind direction (clockwise), the wedging action does not take place and brake 20 applies a negligible braking force to oppose the rewinding operation.
The actual amount of braking force applied to the rim of flange 14 can be adjusted, as shown in FIG. 4, by adjusting the clearance between braking disk 32 and shaft 33. Since the circular brake shoe 32 rotates on shaft 33 when it engages the moving flange 14, the braking action is governed by the difference in frictional forces of disk 32 rotating on shaft 33 and rubbing on the rim of flange 14. If the brake shoe 32 is press-fit to shaft 33, little slippage takes place around shaft 33 and the braking force applied to the rim of flange 14 is greater. At some point, the braking action becomes self-locking and the reel 2 jerks to an immediate stop. With a clearance fit on shaft 33, deceleration is smooth and constant. Such a smooth deceleration is preferred since variations in tension or temporary removal of the tension on wire 4 does not cause the reel 2 to come to a jerking stop.
In FIG. 2 there is shown a partial assembly of the reel 2 with the outer flange 12 removed as well as the wire coil 4. It can be seen that the hub 40 of flange 14 has a number of wedged-shaped ribs 42 on the outer periphery thereof. The outer envelope of ribs 42 conforms to the inner contour of wire coil 4 and thus ensures a snug fit of the coil core. Flange 14 also includes a threaded bushing 44 through which shaft 6 extends. Flange 14 is attached to shaft 6 by a snap ring 46 and is therefore free to rotate on shaft 6.
In FIG. 3 there is shown the outer flange 12 disassembled from the reel to show the outer hub 48 having a diameter which permits it to telescope into hub 40 of flange 14. Within outer hub 48 is an internally threaded inner hub 50 designed so that the internal threads mate with the external threads on bushing 44. Inner hub 50 is supported by a plurality of ribs 52 extending from hub 50 to hub 48.
It will be noted that reel 2 is designed to rotate in a counterclockwise direction during unreeling operations. The threads on bushing 44 and hub 50 are such that flange 12 moves towards flange 14 when flange 12 is rotated in a counterclockwise direction with respect to flange 14. Outer flange 12 can be removed from inner flange 14 by turning flange 12 in a clockwise direction. This permits the removal of flange 12 and the insertion of a wire coil 4 over the hub 40 of flange 14. Outer flange 12 can then be reaffixed to inner flange 14 by turning flange 12 in a counterclockwise direction.
During operation, when inner flange 14 is decelerated by the braking action of brake 20, outer flange 12 tends to continue counterclockwise rotation in response to centrifugal force. This counterclockwise rotation with respect to inner flange 14 moves flange 12 on its threaded hub toward flange 14. The lateral movement of outer flange 12 toward flange 14 maintains a constant lateral force on coil 14, preventing the wires of coil 4 from becoming loose during the unreeling operation. In accordance with the present invention, this lateral tensioning takes place automatically in response to normal braking and without intervention of an operator.
It will be noted that flanges 12 and 14 include no open spaces which would provide safety hazards for personnel using the reel. In the preferred embodiment, the flanges 12 and 14, support arm 8 and base 10 are fabricated from foamed plastic by a foam molding technique to reduce the weight and cost of the reel assembly. A material suitable for this purpose is a thermoplastic polycarbonate manufactured by the General Electric Company under the trade name "Lexan."
It will be noted that the self-braking and self-tensioning properties of the reel of the present invention are independent of the size of the reel or the nature of the coiled material being unreeled. The present invention may therefore find application for very small reels, such as spools of thread in a sewing or weaving application, and for very large reels, such as in a telephone cable reels or wire stock feed reels for automatic screw machines.
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A self-tensioning wire reel comprises two flanges threaded together such that, when a brake shoe applies a braking force to one flange, the other flange is free to continue rotating. This rotation on the threaded hubs brings the flanges closer together, exerting a lateral force on the wire coil therebetween and thus keeping the coil sufficiently tight to prevent binding during the unreeling operation. The brake shoe is a resilient cylindrical disk applied to the outer rim of one flange when tension is relieved on the wire. The tightness of fit between the disk brake and the shaft upon which it rotates controls the frictional braking force.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the benefit of U.S. provisional application 61/129,839, filed on Jul. 23, 2008, the contents of which is hereby incorporated by reference in its entirety.
STATEMENT OF GOVERNMENT FUNDING
[0002] This invention was made with Government support under Grant No. IR01CA124633-01-5 awarded by the National Institutes of Health. The U.S. Government therefore has certain rights in the invention.
FIELD OF THE INVENTION
[0003] The present invention is concerned with methods of treating patients with cancers in which there has been a chromosomal rearrangement that results in a fusion between the NUT (nuclear protein in testis) gene, and a bromodomain gene (BRD3 or BRD4) or other, as yet uncharacterized fusion partner genes. In particular, it is directed to the treatment of these patients with agents that promote increased histone modification, especially acetylation by histone deacetylase inhibitors.
BACKGROUND
[0004] NUT Midline Carcinoma
[0005] NUT midline carcinoma, or “NMC,” is a rare form of cancer characterized by a chromosomal rearrangement in which a portion of the NUT (nuclear protein in testis) gene on chromosome 15 is fused to a BRD (bromodomain protein) gene or other, as yet unidentified, gene (French, et al., Cancer Res. 63(2):304-307 (2003); French, et al., J. Clin. Oncol. 22(20):4135-4139 (2004); French, et al., Oncogene 27(15):2237-2242 (Apr. 3, 2007)). NUT fusion genes encode oncoproteins that maintain cells in an undifferentiated state and promote their rapid and uncontrolled growth. The frequent involvement of midline structures in the head, neck, mediastinal, and other midline structures, suggest that NMCs arise from primitive neural crest-derived cells. NMCs are very aggressive clinically, respond poorly to conventional chemotherapy, and are almost uniformly fatal.
[0006] BRD4 was originally named MCAP (Mitotic Chromosome-Associated Protein) because it remains bound to chromatin via its two bromodomains during mitosis. It is thought to bind in the region of actively transcribed genes before mitosis, thus providing a kind of cellular memory that ensures re-initiation of transcription from these sites after mitosis is completed. Two recent studies provide evidence that this may indeed be the case (Yang, et al., Mol. Cell Biol. 28(3):967-76 (2008); Mochizuki, et al., J. Biol. Chem. 283(14):9040-9048 (2008)). The function of BRD3 is less well characterized but, like all proteins in the BRD family, it contains two acetyl-histone-binding bromodomains and an extra terminal domain (Wu, et al., J. Biol. Chem. 282(18):13141-13145 (2007); Thorpe, et al., Gene 200(1-2):177-183 (1997)). BRD3 is highly homologous to BRD4 and so its involvement in NMC is not unexpected. About two thirds of NMCs result from fusion of NUT to BRD4, and the remaining result from fusion of NUT to BRD3 or other, as yet uncharacterized, gene (French et al., Oncogene 27 (15):2237-2242 (Apr. 3, 2007)).
[0007] In contrast to BRD proteins, NUT lacks known functional domains, is poorly conserved, and is apparently restricted to mammals. Although NUT normally shuttles between the nucleus and cytoplasm, it remains bound to chromatin when fused to BRD4 or BRD3 (French, et al., Oncogene 27(15):2237-2242 (Apr. 3, 2007)). This suggests that the BRD moiety of the fusion protein serves to tether NUT to chromatin, thus modifying the function of either or both proteins in a way that affects transcription. One important consequence of BRD-NUT expression has been discovered using siRNA to silence the expression of BRD3- or BRD4-NUT in NMC cell lines. It was found that withdrawal of the NUT fusion proteins resulted in irreversible squamous differentiation and arrested growth (French, et al., Oncogene 27(15):2237-2242 (Apr. 3, 2007)). These findings suggest that BRD-NUT proteins block differentiation.
[0008] Histone Deacetylase Inhibitors
[0009] During the last few years, it has become increasingly clear that the acetylation of histones plays a central role in the structure of chromatin and gene regulation. Acetylation reduces the positive charge of histones, thereby relaxing the structure of the nucleosome and facilitating the interaction of transcription factors with DNA. Removal of the acetyl group restores the positive charge, thereby causing the nucleosome to contract and become less accessible to transcription factors (Wade et al., Trends Biochem. Sci. 22:128 132 (1997); and Wolffe, Science 272:371-372 (1996)).
[0010] Histone deacetylases (HDACs) catalyze the removal of acetyl groups from histones and appear to play a particularly important role in regulating gene expression. HDACs are segregated into four functionally related classes based on sequence homology to characterized yeast proteins Inhibition of class I HDACs has been actively pursued as an anticancer strategy due to epigenetic changes that affect gene expression in cancer cells. At least one HDAC inhibitor, vorinostat, has been approved by the FDA for use in certain cancers. Activity has been documented in hematologic malignancies, in particular, cutaneous T-cell lymphoma (Minucci, et al., Nature Reviews 6(1):38-51 (2006); Duvic, et al., Blood 109(1):31-39 (2007)). Dose-limiting toxicities for this class of drug include fatigue, nausea, lethargy and myelosuppression, in particular thrombocytopenia.
SUMMARY OF THE INVENTION
[0011] The present invention is based upon the discovery that cancer cells carrying BRD-NUT chromosomal rearrangements respond to histone deacetylase (HDAC) inhibitors by becoming more differentiated and slowing their rate of growth. Thus, HDAC inhibitors should be effective in treating NUT midline carcinoma, a rare cancer that is characterized by the presence of these rearrangements.
[0012] In its first aspect, the invention is directed to a method of treating a patient that has been diagnosed as having a cancer characterized by cells with a chromosomal translocation involving NUT (e.g., BRD4-NUT or BRD3-NUT) or by the presence of bromodomain proteins that exist as translocation partners (or that are fused to proteins critical to transcription) by administering a therapeutically effective amount of a compound that promotes modification, especially increased acetylation, of histones. The most preferred compounds are histone deacetylase (HDAC) inhibitor compounds such as SAHA, FK-228, LBH-589, CRA-024781 (also called PCI-24781), and MS275, but small interfering RNAs may also be used either alone or in conjunction with HDAC inhibitors. The term “therapeutically effective amount” means that sufficient compound is given to a patient to slow or halt the rate of tumor growth or cause a reduction in tumor volume. A therapeutically effective amount may also be evidenced by cells assuming a more differentiated phenotype, which may be manifested paradoxically and temporarily as an increase in tumor volume. In general, it is expected that a patient will be administered a daily dose of 1-2000 mg of HDAC inhibitor, preferably a daily dose of 10-1000 mg, and more preferably 50-600 mg. The cancers containing NUT rearrangements will typically be carcinomas of the aerodigestive tract or mediastinum, especially cancers of the trachea; pharynx; thymus; nasal cavity; thorax; sinuses; or larynx. However, cancers with NUT rearrangement also occur less frequently in other locations, such as bladder and bone.
[0013] The invention also encompasses methods of treating a patient for a solid tumor in which cells from the tumor are first assayed to determine whether they carry a NUT chromosomal rearrangement. If this assay indicates that the chromosomal rearrangement is present, the patient is administered a therapeutically effective amount of compound that promotes increased acetylation of histones. Although any assay, including immunohisto-chemistry demonstrating NUT expression, may be used to determine whether cells carry a NUT rearrangement, the preferred assay is a fluorescence in situ hybridization (FISH) assay or conventional cytogenetics. As discussed above, histone deacetylase (HDAC) inhibitors, e.g., SAHA, FK-228, LBH-589, CRA-024781, and MS275 are the most preferred therapeutic compounds but other compounds promoting increased acetylation may also be used. Preferred dosages and types of cancers most typically treated are given above.
[0014] In another aspect, the invention encompasses methods of determining whether cancer cells will respond to a histone deacetylase inhibitor by performing an assay (preferably a FISH assay) to determine if the cells have a NUT chromosomal rearrangement or express NUT or a NUT-fusion protein.
[0015] The invention encompasses multiwell assay plates containing serial dilutions of at least one, and preferably 5 or more, histone deacetylase (HDAC) inhibitors (or compounds being tested for NMC activity), each well having only one species of compound. Examples of compounds that may be bound to wells include: CRA-024781; APHA; bortezomib; Apicidin, CI-994; FK228; HC-Toxin; ITF2357; LAQ824; LBH589; MGCD0103; MS275; Niltubacin; Oxamflatin; PXD101; Pyroxamide; SAHA; Scriptaid; TSA; Tubacin; Nialamide; PBA; PBHA; Phenylzine; Tranylcypromine; VPA; and VPHA. Preferred compounds are CRA-024781, SAHA, FK-228, LBH-589 and MS275. The plates may be used for testing the responsiveness of NMC cells to treatment by each of the bound compounds. This may be accomplished by: a) incubating test NMC cells in the wells of the multiwell assay plate; b) assaying the test cells in each well to determine proliferation; histone acetylation; and/or expression of a protein (such as keratin) characteristic of cells that have become differentiated; and c) concluding that the NMC cells are responsive to the compound present in an assay well if the assay of step b) indicates that, relative to control NMC cells incubated under the same conditions but in the absence of compound, the test NMC cells exhibit reduced proliferation, increased histone acetylation and/or increased expression of a protein that identifies cells that have become differentiated. In a preferred embodiment, the cells are analyzed using antibody that recognizes acetylated histones or keratin.
DETAILED DESCRIPTION OF THE INVENTION
[0016] NUT midline carcinoma (NMC) is a rare, highly lethal cancer that occurs in children and adults of all ages. NMCs occur in the midline, most commonly in the head, neck, or mediastinum, as poorly differentiated carcinomas with variable degrees of squamous differentiation. This tumor is defined by rearrangement of the “nuclear protein in testis” (NUT) gene on chromosome 15q14. In most cases, NUT is involved in a balanced translocation with the BRD4 gene on chromosome 19p13.1, an event that creates a BRD4-NUT fusion gene. Variant rearrangements, some involving the BRD3 gene, occur in the remaining cases. NMC may be diagnosed by detection of NUT rearrangement by fluorescence in situ hybridization, karyotype analysis, or RT-PCR. Due its rarity and lack of characteristic histologic features, most cases of NMC currently go unrecognized.
[0017] NMC Defined Molecularly
[0018] NMC is defined herein as any malignant epithelial tumor with rearrangement of the NUT gene. In approximately ⅔ of cases, NUT (chromosome 15q14) is fused to BRD4, on chromosome 19p13.1, forming the BRD4-NUT fusion gene. In the remaining ⅓ of cases, the partner gene is BRD3 or other uncharacterized gene. We term these NUT-variant fusion genes. The histologic features of NMC are not distinctive, and diagnosis is based on detection of the NUT rearrangement. NUT rearrangements define NMCs, and for this reason the diagnosis is never in question once rearrangement of NUT has been demonstrated.
[0019] Diagnosis
[0020] As noted above, normal NUT expression is restricted almost exclusively to the testis. Thus, positive nuclear immunohistochemical (IHC) staining for NUT in tissues outside the testis is indicative of aberrant expression, such as in NMCs, where both BRD4-NUT and NUT-variants localize to the nucleus. Testing of rabbit polyclonal NUT antibodies for diagnostic utility using a panel of five NMCs and twenty-three NUT-unrelated poorly differentiation carcinomas of the upper aerodigestive tract suggests a specificity of 95% and a sensitivity of 60%. This may be somewhat less sensitive than one would like in a diagnostic test that is envisioned as a screen for the selection of tumors for confirmatory FISH testing. However, NUT monoclonal antibodies may permit the development of a more sensitive, IHC-based diagnostic screening test.
[0021] Assays for Chromosomal Rearrangements
[0022] In order to carry out assays to determine whether a NUT rearrangement has occurred in a cancer, tumor cells must first be obtained, e.g., by fine needle aspiration or a tissue biopsy. Any assay may then be used to determine whether cells are present having a rearrangement of the type discussed above. For example, the polymerase chain reaction may be used to amplify sequences in regions that would indicate that a fusion has occurred (Engleson, et al. BMC Cancer 6:69 (2006), incorporated herein by reference in its entirety). The preferred assay is the fluorescence in situ hybridization (FISH) assay described in French et al., Am. J. Pathol. 159:1987-1992 (2001) and French et al., Oncogene 27 (15):2237-2242 (Apr. 3, 2007), incorporated herein by reference in their entirety. This dual color, split-apart assay is performed on frozen tissue, air-dried cells, methanol-acetic acid preparation of metaphase-arrested cells, formalin-fixed, paraffin-embedded, unstained, 4-μm sections of tumor, or formalin-fixed, paraffin-embedded, unstained disaggregated thick (50 um) sections of tumor. Probes used for the BRD4 breakpoint on chromosome 19p13.1 break point included telomeric bacterial artificial chromosome (BAC) clone 87m17 (green) and centromeric yeast artificial chromosome (YAC) clone 766e7 (red). Presently, telomeric tandem BACs, RP11-319010 and RP11-681d10, and centromeric tandem BACs, RP11-207i16 and CTD-3055m5 are used to assay for the BRD4 breakpoint. Probes used for the 15q13 break point (NUT), flanking a 181-kb region, include telomeric BAC clones 1H8 and 64o3 (green) and centromeric clones 412e10 (recently replaced with 1084a12) and 3d4 (red). Probes used for the BRD3 (chromosome 9q34.2) include telomeric BAC clone 145e17 (green), and centromeric BAC clone 2243h5 (red).
[0023] HDAC Inhibitors
[0024] Treatment methods described herein include the use of HDAC inhibitors. These compounds have been very extensively studied in the treatment of several diseases, including various types of cancer. As a result, a very large number of inhibitors have been developed and some are commercially available. Compounds that may be used in connection with the present invention are described in: U.S. Pat. Nos. 7,381,825; 7,381,749; 7,375,228; 7,375,137; 7,368,572; 7,345,043; 7,312,247; 7,291,492; 7,288,567; 7,282,608; RE39,850; 7,271,195; 7,265,154; 7,253,204; 7,250,514; 7,250,504; 7,244,751; 7,214,831; 7,205,304; 7,193,105; 7,169,801; 7,154,002; 7,135,493; 7,091,229; 7,057,057; 6,905,669; 6,897,220; 6,673,587; 6,638,530; 6,541,661; 6,495,719; 20080146623; 20080139547; 20080139535; 20080132503; 20080132459; 20080112889; 20080108601; 20080096920; 20080039509; 20080033015; 20080015216; 20080015190; 20070293530; 20070292351; 20070281934; 20070213330; 20070149495; 20070142393; 20070135438; 20070135431; 20070135424; 20070122507; 20070105808; 20070037869; 20060264415; 20060235231; 20060199829; 20060167103; 20060148743; 20060106049; 20060052599; 20060047123; 20060030554; 20060030543; 20060020131; and 20050288282. All of these references are hereby incorporated by reference in their entirety.
[0025] Pharmaceutical Compositions
[0026] The therapeutic compounds described herein may be incorporated into pharmaceutical compositions in accordance with methods that are standard in the art (see e.g., Remington's Pharmaceutical Sciences, Mack Publishing Co., (1990)). Formulations may be designed for delivery by any of the routes commonly used in the art.
[0027] Therapeutic compounds may be used in conjunction with any of the vehicles and excipients commonly employed in pharmaceutical preparations including water, salt solutions, alcohols, gum arabic, vegetable oils, benzo-alcohols, polyethylene glycol, gelatin, carbohydrates such as lactose, amylase, or starch; magnesium stearate; talc; salycic acid; paraffin; fatty acid esters; polymers; etc. The pharmaceutical preparations can be sterilized and, if desired, mixed with auxiliary agents such as: dispersants; lubricants; preservatives; stabilizers; wetting agents; emulsifiers; salts for influencing osmotic pressure; buffers; coloring agents; flavoring agents; and/or aromatic substances.
[0028] Solutions, particularly solutions for injection, can be prepared using water or physiologically compatible organic solvents such ethanol, 1,2-propylene glycol; polyethylene glycol; polygycols; dimethylsulfoxides; fatty alcohols; triglycerides; partial esters of glycerine; and the like. The preparations can be made using conventional techniques and may include sterile isotonic saline, water, 1,3-butanediol, ethanol, 1,2-propylene glycol, polygycols mixed with water, ringers Ringer's solution etc.
[0029] Dosage Forms and Routes of Administration
[0030] The present invention is compatible with any route of administration including oral, peroral, internal, rectal, nasal, lingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal, intracutaneus, and subtaneous routes. Dosage forms that may be used include tablets, capsules, powders, aerosols, suppositories, skin patches, parenterals, sustained release preparations and oral liquids, including suspensions solutions and emulsions. The most preferred routes for administration are oral, by injection, or by infusion.
[0031] If desired, compositions, particularly compositions for injection, may be freeze-dried and lyophilizates reconstituted before administration. Dosage forms may include compounds promoting an increase in histone acetylation as the sole active ingredient or may include other active agents as well. All dosage forms may be prepared using methods that are standard in the art and that are taught in reference works such as Remington's Pharmaceutical Sciences (Osol, A, ed., Mack Publishing Co. (1990)).
Examples
[0032] The results obtained from experiments, and conclusions drawn based on the results, may be summarized as follows:
[0033] A. Association of BRD-NUT with Decreased Acetylation and Transcription
[0034] Expression profiling was performed using two NMC cell lines, TC-797 (Toretsky, et al., Am. J. Clin. Oncol. 26(3):300-306 (2003)) and PER-403 (Kees, et al., Am. J. Ped. Hematol./Oncol. 13(4):459-464 (1991)) treated with control or NUT siRNA. Twenty-four hours following knockdown of BRD4-NUT in the two NMC cell lines, prior to the phenotypic features of differentiation, the number of upregulated genes was found to vastly outnumber the number of genes that are downregulated, as quantified on whole-genome expression array chips (Affymetrix HGU-133 plus 2.0).
[0035] Immunoblots of the NMC cell lines TC-797 and PER-403 (Kuzume, et al., Intn'l J. Cancer 50(2):259-264 (1992)) treated with NUT siRNA or control siRNA revealed a global increase in acetylated histone H4, H3K18, and H4K8 in response to NUT siRNA. Consistent with this was a finding that 293T cells containing a Tet-inducible BRD4-NUT construct showed globally reduced staining for the same acetyl-histone marks in response to BRD4-NUT induction.
[0036] Consistent with a role in transcriptional repression, BRD4-NUT exhibits dominant-negative activity on a BRD4 transcriptional target, an HIV LTR-driven luciferase reporter gene.
[0037] B. Reversing BRD-NUT-Induced Chromatin Remodeling
[0038] Immunostaining experiments were performed to compare the spatial distribution of acetylated chromatin with that of BRD4-NUT in situ. It was found that acetylated chromatin, in the absence of BRD4-NUT, is diffusely distributed throughout the nucleus. In contrast, in the presence of BRD4-NUT, acetylation marks become speckled and co-localize with BRD4-NUT.
[0039] C. HDAC Inhibition in NMC
[0040] Studies aimed at testing the hypothesis of HDAC inhibitor therapy in NMC have been conducted using trichostatin A (TSA), and vorinostat (SAHA, Zolinza®). Both of these compounds are regarded as non-selective for class I and II deacetylases and bind HDAC proteins by chelating the active site zinc atom with a hydroxamic acid feature. NMC cells cultured in vitro were treated with TSA in dose- and time-ranging studies. Using immunofluorescence microscopy, it was found that there was an increase in histone acetylation with increasing dose and time of exposure. Interestingly, a redistribution of both BRD-NUT and acetylation marks from nuclear speckles to a diffuse pattern was also observed. With further drug exposure, a differentiation phenotype was observed by bright-field microscopy and by immunohistochemistry for the epithelial differentiation-associated protein, keratin. Within 24 hours following TSA (25 nM), NMC cell lines rapidly differentiate, as assessed by brightfield microscopy, in a manner similar to that seen when BRD-NUT is inhibited with specific siRNAs. Specifically, TSA caused changes in cellular morphology and increases in cytoplasmic keratin staining that are consistent with squamous differentiation.
[0041] These findings suggest that TSA treatment phenocopies direct interference with BRD-NUT. Consistent with an effect of TSA due to HDAC inhibition, rather than off-target effects or secondary toxicities, treatment of five NMC cell lines with pharmacologic doses of suberoylanilide hydroxamic acid (SAHA), an FDA-approved HDAC inhibitor with a spectrum of activities similar to that of TSA (class I and HDAC6 inhibition), also resulted in differentiation and arrested growth.
[0042] D. Assembly of Chemical Library of HDAC Inhibitors
[0043] In order to explore the response of NMC cells to HDAC inhibitors, we assembled a library of compounds shown in Table 1. Compounds were either purchased commercially or chemically synthesized and plated in serial dilutions (384 wells) with appropriate numbers of control, and solvent-only wells.
[0000]
TABLE 1
Pharma HDAC Inhibitor Library
Name
Chemotype
APHA
Hydroxamic acid
Apicidin
Ketone
CI-994
Hydroxamic acid
CRA-024781
Hydroxamic acid
FK228
Thiol
HC-Toxin
Epoxide
ITF2357
Hydroxamic acid
LAQ824
Hydroxamic acid
LBH589
Hydroxamic acid
MGCD0103
Benzamide
MS275
Benzamide
Niltubacin
Carboxylic acid
Oxamflatin
Hydroxamic acid
PXD101
Hydroxamic acid
Pyroxamide
Hydroxamic acid
SAHA
Hydroxamic acid
Scriptaid
Hydroxamic acid
TSA
Hydroxamic acid
Tubacin
Hydroxamic acid
Nialamide
MAOI
PBA
Carboxylic acid
PBHA
Hydroxamic acid
Phenylzine
MAOI
Tranylcypromine
MAOI
VPA
Carboxylic acid
VPHA
Hydroxamic acid
[0044] E. Development of High-Throughput, High-Content Assays
[0045] A cell based approach was developed for identifying potent and selective HDAC inhibitors. Nuclear acetylation correlates with inhibition of class I deacetylases such as HDAC1 and HDAC2. An automated epiflourescent assay was therefore developed which is measures histone hyperacetylation. Cells were seeded in 384-well plate format (500 cells/well) and treated with compound. They were then fixed and stained with: a) Hoechst (nuclei); b) primary anti-AcHistone polyclonal Ab; c) anti-Keratin monoclonal antibody; and d) compatible flurophore-conjugated secondary antibodies. After automated image acquisition, a custom analysis program was applied that identifies and masks cells based on nuclear intensity (Hoechst) and then derives quantitative fluorescent data from the FITC (AcHistone) image. Subsequent secondary masks were generated using cytosolic intensity.
[0046] F. Adaptation of the Screening Assay (HCS) to NMC Culture.
[0047] We have performed studies of HDAC inhibitor effects on NMC cells in culture using an adaptation of the assay described above. In studies of the effect of SAHA on NMC (TC797) cells in a 384-well plate format, we have observed increased histone acetylation qualitatively in images derived from dose-ranging experiments. In a first attempt at multiplexed detection and quantification of effects on cell proliferation, histone acetylation, and keratin protein expression, we have witnessed clear, dose-response activity of SAHA in the pharmacologically achievable range (C. approximately 2 μM). It was found that SAHA caused a reduction in cell proliferation and an induction of increased keratin protein content that correlated with an increase in histone acetylation (R 2 =0.99).
[0048] All references cited herein are fully incorporated by reference. Having now fully described the invention, it will be understood by those of skill in the art that the invention may be practiced within a wide and equivalent range of conditions, parameters and the like, without affecting the spirit or scope of the invention or any embodiment thereof.
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The present invention is directed, inter alia, to methods of treating NUT midline carcinoma (NMC) by administering compounds that promote increased histone acetylation. The invention also includes assay methods for determining the responsiveness of NMC to specific histone deacetylases and other compounds.
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RELATED APPLICATIONS
This is a continuation of application Ser. No. 439,430, filed Nov. 5, 1982, and now issued as U.S. Pat. No. 4,616,771, which was in turn a divisional of application Ser. No. 88,864, filed Oct. 29, 1979, and also issued as U.S. Pat. No. 4,358,037.
BACKGROUND
1. FIELD
This invention is in the field of vehicle-mounted luggage carriers. It relates in particular to improvements in the type of carrier which has two or more low with each slat a pair of slidable, lockable tie-downs.
2. PRIOR ART
Earlier luggage carriers of the permanently affixed type simply provided an enclosed area of luggage, often with fixed, elevated siderails and with endrails or crossbars that were slidable fore and aft along the siderails. In some cases mechanisms were provided for clamping the slidable endrails at particular positions along the siderails, and in some cases eyelets were provided in the siderails for securing ropes. Examples of these types appear in U.S. Pat. No. 3,554,416, filed in 1968 and issued to Bott in 1971.
By 1970 it was becoming customary to protect the vehicle surface with permanently affixed slats, of shallow cross-section, to support the luggage. Such a construction appears, for example, in U.S. Pat. No. 3,623,642, issued in 1971 to James Stephen.
Some of the slats used for this purpose were made of roll-formed sheet metal. In certain particular roll-formed designs, each slat, viewed in lateral cross-section, consisted of a pair of upstanding outer walls, a pair of upstanding inner walls spaced inward from the outer walls, two substantially horizontal (but sometimes arched) top supporting surfaces spanning the gap between each outer wall and its adjacent inner wall, and a recessed horizontal "web" portion connecting the bottom ends of the two inner walls. The luggage load was supported solely upon the two outer walls of the roll-formed sheet-metal slat, the inner walls being shallower and the "web" being elevated above the vehicle surface or any intermediate plastic or rubber mounting pad. Thus the principle purpose of the two inner walls and intervening web was to give the structure rigidity and style, and permit use of an adhesive-affixed or snap-in plastic trim strip down the recessed center of the slat, between the inner walls. Examples of such pre-1973 support slats were those in general production by the Amco Manufacturing Corporation, of North Hollywood, Calif., and others in use on Ford automobiles.
Commercial popularity later shifted to structures more compatible with the low, streamlined styling of modern vehicles. The upstanding siderails disappeared, and the tie-down function was transferred to the slats--which now extended most of the length of the mounting surface, and were either roll-formed sheet metal or extrusions. With this general design shift came an assortment of drawbacks:
Because the slats were very low and shallow, they were not readily amenable to attachment of cord or rope, so it became necessary to provide tie-downs affixed stationarily or slidably to the slats. (By "tie-down" is meant a loop, eye, hook or similar structure about or through which a rope or the like may be tied, strung or otherwise fastened. By "rope or the like" is meant a rope, cable, chain, strap, webbing, elastic cord, thong, or other elongate, generally but not necessarily nonrigid securing element--whether or not provided with an attached eye, hook or other fastening termination.) Stationary tie-downs proved inconvenient in use. Slidable tie-downs were attached either by means of external tracks or flanges along the top upper edges of the slats, or by making use of the central groove--previously used only for trim strips or other visual effects. One natural way to make use of the groove was to form it with a previously well-known conventional dovetail cross-section, or other comparable well-known retaining cross-section, so that it could hold a complementarily shaped nut slidably captive, and thus provides a slidable attachment for a tie-down. Unfortunately both types of slidable tie-down were incompatible with the snap-in plastic trim strips mentioned earlier. If the tie-downs were connected by means of external tracks, the clamping screws engaged and marred the finish of the trim strips. If the tie-downs were connected by means of shaped nuts which slid in a dovetail or other retaining groove, the trim strip had to be removed to permit sliding of the nuts and tie-downs along the slats.
Elevated crossbars were of course still necessary for certain specialized uses, and it was standard practice to attach these to the slats temporarily by the same or similar sliding elements as used for the tie-downs. This attachment arrangement in general serves a useful purpose, and has found extensive commercial use. However, with the added leverage of the crossbars the clamping mechanisms holding the tie-downs to the slats could work loose, permitting the crossbars to slide along the slats--and this in turn could lead to damage of the retaining nuts, the slats, or even the vehicle top or luggage.
Representative of this generation of carriers are U.S. Pats. Nos. 4,015,760 and 4,099,658, both to Bott, issued in 1977 and 1978 respectively, and 4,132,335, which issued in 1979 to Ingram. Some features of the last two patents mentioned represent efforts to resolve some of the drawbacks mentioned, but because of more solid or more elaborate construction these features are objectionably costly.
OBJECTIVES OF THE INVENTION
The present invention is directed to resolution of the drawbacks outlined above, at moderate expense, in a luggage carrier compatible with modern standards of styling and streamlining.
More particularly, it is an object of the invention to provide a slidable, lockable bracket for use in a vehicle-mounted luggage carrier having a plurality of slats, each slat being formed with external tracks along its opposite edges, which bracket is compatible with decorative trim along the centers of such slats and provides a means of attachment for a tie-down or a crossbar.
Another object of the invention is to provide a luggage-restraining device which, though adapted to prevent luggage from sliding along the slats of such a carrier, is also adapted to assume when not in use a low-profile configuration with respect to such slat, for stylish appearance and minimal wind resistance.
Yet another object of the invention is to provide a system for attachment of a crossbar between a pair of slats of such a carrier, whereby the previously mentioned slidable, lockable bracket provides a means of attachment for the crossbar but attachment is possible only at a very small, limited number of discrete points along the slats--at which points additional provision is made for overcoming the natural tendency of weight applied to the crossbars, acting through the crossbar leverage, to dislodge the bracket locking mechanism.
A further object of the invention is to provide accessories for use in carrying particular items which are cumbersome or awkward to secure to such a vehicle carrier but which it is particularly often desired to carry on a vehicle--such as, for example, a bicycle or skis.
One yet further object of the invention is to provide in combination all of the components of a vehicle-mounted carrier which implements the several objects enumerated above.
The manner in which my invention implements these objects may be understood and appreciated by reference to the following detailed description and the accompanying drawings, of which:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an isometric elevation showing a preferred embodiment of the present invention, installed on the top of a vehicle.
FIG. 2 is an enlarged view, also isometric but partly cut away for clarity, of part of the FIG. 1 embodiment.
FIG. 3 is a similar enlarged view of another part of the FIG. 1 embodiment.
FIG. 4 is an elevation, principally in cross-section, taken along the line 4--4 of FIG. 3.
FIG. 5 is an isometric view of the preferred embodiment of FIG. 1 in use with an accessory which facilitates carrying of a bicycle.
FIG. 6 is an enlarged view of part of the accessory shown in FIG. 5.
FIG. 7 is an isometric view of the preferred embodiment of FIG. 1, but with part of that preferred embodiment removed and replaced by an accessory which facilitates carrying skis.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Generally speaking, the instant invention is a vehicle-mounting multipurpose carrier, taking the form of several modular elements which can be used in various combinations and ways to quickly and easily accommodate a great variety of items to be carried. However, the basic carrier--designed to remain permanently attached to the vehicle--is a low, streamlined structure which harmonizes and cooperates with modern vehicle styling.
Four parallel roll-formed slats attached to a vehicle top or rear deck have external tracks formed along their opposite edges. On each slat is a pair of brackets, which engage the external tracks of the sslat, and are slidable along substantially the whole length of the slat and lockable at any point along the sliding range. The brackets each comprise a housing which engages the external tracks, an intermediate clamping member retained within but movable with respect to the housing, and means for applying force between the housing and the clamping member to press the clamping member against the tracks. This arrangement permits locking the brackets along the slat without marring a plastic trim strip which is retained in a central groove in the slat.
The four brackets which slide along the two inner slats are each provided with hinged end-stops which can be turned up to engage and restrain luggage, or when not in use turned down to closely hug the slats--minimizing wind resistance and presenting a trim appearance.
The brackets which slide along the two outer slats are each provided with tie-downs for use with rope or the like, and in addition are adapted to support special-purpose crossbars spanning the outer slats. These crossbars are attachable to the brackets only when the latter are in certain discrete positions (related to the crossbar functions) where extra resistance to sliding is provided. Special clamps are provided for securing bicycles by their handlebars to one crossbar, with the bicycle seat held against the other crossbar by straps or elastic cord. Another type of crossbar is a ski-rack type, with a key-releasable ski clamp.
The principal modules of a preferred embodiment of the invention appear in FIG. 1.
Two outer or outboard slats 11, mutually parallel, are affixed permanently as by screws or rivets to the top 10 of a vehicle. Two inner or inboard slats 21 are similarly affixed to the vehicle top 10, between and generally parallel to the outer slats 11. The inboard slats 21 may be omitted, or additional ones added, as preferred.
Slidably fastened to each outboard slat 11 are two tie-down brackets 31, which are capable of being moved to any position along the respective slat 11 and locked in that position using an internal clamping mechanism, to be described.
Also fastened to the outboard slats 11, and spanning those slats, are two crossbars 41. The crossbars 41 are optionally and removably attached to the slats 11 by means of the respective brackets 31; however, the slats 11 and attachment means are adapted for this attachment only at a limited number of specific locations along the length of the slats 11. Two of these locations are illustrated in FIG. 1, and two other in FIG. 7. Another application using one of the location illustrated in FIG. 1 and one of those illustrated in FIG. 7 appears in FIG. 5. Thus there are four positions in which the crossbars 41 can be attached to the slats 11; at these positions, as will be seen, a location reinforcement mechanism is provided, so that the crossbars and any weight placed on them do not depend solely on the bracket-clamping device mentioned earlier to maintain correct positioning of the crossbars along the slats.
The four positions at which crossbar attachment is permitted and position reinforcement is provided are selected for optimum use of certain accessories to be described hereunder, and in the case of the general-purpose crossbars shown in FIG. 1 simply as generally optimum locations for use of those crossbars. The crossbars are readily and quickly installed or removed, so that the tie-down brackets 31 can be positioned, locked, and used without the crossbars 41 at any point along the slats 11.
Slidably fastened to each inboard slat 21 are two end-stops 51, each positionable at any point along the respective slat 21 and lockable at that point using an internal clamping mechanism. In addition each end-stop 51 is adapted to be manually moved between two configurations--(1) one position in which the end-stop is upwardly extending for the purpose of engaging luggage placed upon the slats 21 and/or 11, to prevent such luggage from sliding longitudinally with respect to the slats and vehicle; and (2) a second position in which the end-stop is very low, hugging or recessed within the respective slat, to present a trim or "tight" appearance and minimum wind resistance.
Some details of the FIG. 1 construction appear more clearly in FIGS. 2 through 4. As shown in FIG. 2 a preferred construction for the slats 21 (and for the outboard slats 11 as well) is roll-formed sheet metal, and in particular comprises two upstanding outer walls 23, two upstanding inner walls 26, two substantially horizontal top supporting surfaces 25 spanning the gap between each outer wall and its adjacent inner wall, and a horizontal "web" portion 27 connecting the bottom edges of the two inner walls 26. The web portion 27 is recessed relative to the upper surfaces 25, but well above the bottom edges of the outer walls 23. An essential aspect of this embodiment is the flattened outer corner or edge 24 along each side of the roll-formed cell; these flattened portions serve as external gripping surfaces or tracks for slidable attachment of the end-stops 51, as will be seen (and, in the case of the outboard slats 11, for slidable attachment of the tie-down brackets 31). Other features of the slats 21 (and 11) include the inwardly directed rolled edge 22, which helps to preserve the appearance and condition of the metal edge and of the vehicle top 10; and mounting holes such as 28 in the horizontal "web" section 27.
Also helping to preserve appearance and condition of the vehicle top 10 and metal edge is a mounting pad or gasket 76, which has a T-groove section 77 near each outer edge, specially formed to receive the rolled-in edge 22 of outer wall 23. The mounting pad also has a continuous flat web section 78, connecting and stabilizing the T-groove sections. It will be noted that the web section 78 of gasket 76 is flat and shallow, and does not engage the underside of the corresponding metal web section 27; thus any weight placed upon the slat 21 (or 11) is supported entirely by the outer walls 23, the inner walls 26 contributing no support.
Additional plastic trim features are end-cap 72 and trim strip 73. The end-cap 72 may be made in such a way that it blocks the end of the track 24, so that the end-stop 51 (or brackets 31) cannot be slide off the end of the slat. If preferred, however, the end-cap 72 may be made in such a way that it permits the end-stop 51 (or brackets 31) to slide off the end of the slat for separate storage when not in use; this is simply a matter of design preference. The trim strip 73 is a snap-in type, with lips 74 extending beyond the central groove formed by walls 26 and web 27, and retaining protrusions 75 which extend into that groove and exert light retaining pressure against the walls 26.
The end-stop 51 is slidably secured to the slat 21 by means of a sliding bracket 52 which as shown is contoured to clear the trim strip 73 but closely surround, as by inwardly dented portions 54 of downward extensions 55 on each side, the external tracks 24. The end-stop 51 is hinged to the sliding bracket 52 as by rivets 56 on each side, secured to the downward extensions or ears 55 on each side of the bracket 52. This pivoting attachment permits the end-stop 51 to be manually swung down (counterclockwise in FIG. 2) to a position just above and closely hugging the slat 21. For this purpose the end-stop 51 is contoured as at 58 to clear the trim strip 73 when the end-stop 51 is in lowered position; and is swaged or dimpled as at 59 to provide a "snap-action" detent, holding the end-stop firmly against the slat 21 and thus avoiding rattles. The end-stop is cut in as at 61 to exactly the proper distance from the pivot 56, taking into account the height of the bracket 52 above the rivet 56 position, so that the end-stop 51 when hinged upward will stand substantially vertical. The pivot 56 must be at a suitable distance from the end of the bracket (the left end, as drawn in FIG. 2) so that when the end-stop 51 is lowered against the slat 21 the cut-in edge 61 clears the bracket 52--but only by a slight distance, so that an unsightly gap is avoided.
While a preferred embodiment as described above involves a hinge action to accomplish extension and retraction of the end-stop 51 with respect to the bracket 52, other mechanisms for extension and retraction--such as, merely for example, telescoping structures, folding structures, or screw structures--are also workable and within the scope of certain of the appended claims.
The end-stop 51 and its sliding bracket 52 may be locked against the tracks 24 by means of an internal clamping mechanism, mentioned earlier. This mechanism consists of an intermediate clamping plate, visible in FIG. 2 where the bracket 52 housing is cut away at 62, and a set-screw 53 which is recessed within the housing 52. The intermediate clamping plate has two lower edges 66 which engage the upper surfaces 25 of the tracks 24, two generally vertical sections 65 permitting clearance of the trim strip 73, and one generally horizontal intermediate section 63 which is depressed by set-screw 53 when the latter is screwed down into the bracket housing 52. If preferred, the intermediate clamping plate could engage the track surface 25 on only one side of the slat 21, the other edge of the clamping plate being supported internally within the bracket 52.
The foregoing description of the end-stop brackets 52 applies equally well to the tie-down brackets 31 shown in FIGS. 3 and 4, except that, of course, there is no end-stop 51; hinged to each tie-down bracket 31 there is instead a tie-down loop or eye 37, or if preferred a hook or other structure through or about which a rope or the like may be tied, strung or otherwise fastened. Downward extension 35 may as shown be shorter longitudinally than the extensions 55 of FIG. 2. The pivot attachment 36 is by a rivet the like through downward extension or ear 35, and the bracket 31 is contoured to clear the trim strip 73a and closely surround, as by an inwardly angled bottom edge 34 on each side, the external tracks 14 of slat 11. The slat 11 is identical to the slat 21 previously described, except for certain essential locating holes to be mentioned shortly, and is provided with identical plastic end-caps (not shown) and mounting pad 76a--engaging inwardly rolled bottom edge 12 of the slat 11.
However, ther are certain essential differences in the tie-down bracket 31, relative to the end-stop bracket 52. These differences relate to the attachment of crossbars 41:
Upstanding pillar 38, which is integral with the bracket housing 31, provides an anchor point for the crossbar 41. The downward termination 42 of the crossbar 41 comprises a flattened horizontal section 43 adapted to engage the flat horizontal top surface of the bracket 31, while the hole 44 in the horizontal section 43 engages the pillar 38. Pillar 38 is not essential, as screw 45 adequately secures the cross bar 41. The underside of the bracket housing 31 carries a downward extending enlargement 31a below and surrounding the area of the base of the pillar 38. The enlargement 31a adds strength to the structural attachment of the pillar 38, so that force applied to the pillar via the crossbar 41, 42 does not deform or otherwise damage the bracket 31 or attached pillar. A threaded hole 39 passes vertically through the pillar 38, bracket housing 31 and enlargement 31a, accommodating special screw 45 which secures the crossbar to the bracket. The screw 45 has a screwdriver head 46, threads 47 which mate with those of hole 39, and a turned-down (that is to say, smaller-diameter) extension 48 which after installation extends downward beyond the bottom surface of enlargement 31a. The extension 48, when the screw 45 is threaded fully into the mating hole 39, passes through circular holes or short slots 67 in the clamping plates 63a, 79 in the trim strip 73a, and 19 in web portion 17 of roll-formed slat 11. Clamping plate 63a, trim-strip 73a, and web 17 are identical to the corresponding elements 63, 73 and 27 of FIG. 2, with the exception of the respective circular holes or slots 67, 79 and 19. When crossbar 41 is to be attached, tie-down 37 is readily pivoted out of the way to either the right (as drawn in FIG. 3) or left of the pillar 38, to clear the crossbar. The extension 48 interacts with the holes or slots 67, 79 and 19 to permit crossbar attachment only at the particular locations along the slats where the holes are provided; and at those particular locations provide reinforced positioning along the slat, not solely dependent upon the clamping action previously described. This arrangement tends to prevent the bracket 31 from being loosened and slid along the slat 11 by weight or other forces applied to the crossbar 41 and through the leverage of the downward termination 42. The holes or slots also help a user to find quickly the locations along the slat appropriate for the various types of crossbars.
For example, the general-purpose crossbars 41 when used to help secure to support miscellaneous luggage may be placed at the two intermediate locations along the slat illustrated in FIG. 1. The spacing of these locations along the slats in terms of fractions of the slat lengths, or in terms of absolute distances, of course varies with the overall slat lengths and in turn the size of the vehicle surface on which the slats are installed; however, as suggested in FIG. 1 the crossbar attachment points for a relatively large vehicle may be spaced inwardly from the slat ends roughly 30% of the slat length. This spacing is also suitable for use with the bicycle-mounting module shown in FIGS. 5 and 6. Additional crossbar attachment points are provided at the extreme ends of the slat. On a smaller vehicle, as indicated in FIG. 5, it may generally be more appropriate to provide only three crossbar attachment points--one at each end, and one 35% or 40% forward from the rear end. This intermediate attachment in combination with the front end attachment will accommodate a standard bicycle, as illustrated in FIG. 5. For the ski-rack module, as shown in FIG. 7, for almost all autos except station wagons the extreme end locations are most appropriate.
As shown in FIGS. 5 and 6, the bicycle-mounting module consists of the standard outboard slats 11 (the inboard slats not being used, but of course remaining on the vehicle), four tie-down brackets 31, two crossbars 41, two special clamps 91, a pair of stabilizing straps 82 and an elastic cord, sometimes called a "bungy cord," 83. As illustrated a bicycle 81 is positioned upside-down above the vehicle, with the bicycle seat above one of the crossbars 41 and the handlebars 84 above the other crossbar 41. Each of the two clamps 91 is actually a dual-function device, the lower two jaws 92 and 93 being secured to the crossbar 41 and the upper two jaws 93 (through its upward extension 99) and 94 firmly gripping the handlebar 84.
The three jaws 92, 93 and 94 are held together by a pair of bolts 95, the lower two jaws 92 and 93 being held to the crossbar by nuts 97, in cooperation with bolts 95, and the upper jaw 94 being drawn toward the lower two by the action of wing nuts 96. The two bolts 95 pass through holes in the three jaws 92, 93 and 94; one of these holes in the upper jaw 94 is opened outward to one side of the jaw 94 to form a slot 98. This construction permits the upper jaw 94 to be swung out of the way of the handlebar 84 after the wing nuts 96 have been backed only partway up the bolts 95, rather than requiring complete removal of the wing nuts and upper jaw to place the bicycle on the rack or remove it from the rack. The bungy cord 83 holds the seat to the crossbar 41 upon which it rests, and the straps 82 stabilize the bicycle laterally by attachment between the bicycle frame and the tie-down loops 37 on the outboard brackets 31.
The ski-rack module, illustrated in FIG. 7, comprises two substantially identical special-purpose crossbars 141, mounted to the outboard slats 11 and tie-down brackets 31 as previously described for the general-purpose crossbars 41 of FIGS. 1 and 3 through 6. Attached to each crossbar 141 is a ski mount capable of holding and securing a plurality of skis, and comprising a lower bar 147 attached firmly to the crossbar 141, a vertical hinge or pivot 146 secured to one end of the lower bar 147, an upper bar 148 attached at one end to the hinge 146, a pair of compliant pads 149 disposed along the mutually facing sides of the bars 144 and 148, and a locking mechanism at the end of the bars opposite the end where the hinge 146 is.
The locking mechanism may take various forms, one favored embodiment as illustrated comprising a hasp 145 which when in an upper position (as shown at the left in FIG. 7) blocks the upper bar 148 from pivoting vertically in or out of its horizontal position, parallel to the lower bar 147. The hasp 145 may be swung outward (as shown at the right end of FIG. 7) to permit the upper bar 148 to move in and out of the horizontal position. In the preferred embodiment shown, the hasp can be held in its inward position or released by a security lock, contained within lock housing 144 and controlled by a key 143. When the upper bar is moved to its horizontal position, parallel to the lower bar, and secured by the hasp, it firmly but compliantly retains up to six skis side by side, though only two skis 141 are illustrated.
It is intended to be understood that the foregoing discussion of preferred embodiments is offered only by way of example, and not intended to be interpreted as limiting the scope of the invention--which scope is defined by the appended claims.
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Slats fixed to a vehicle deck have external-flange tracks along their opposite edges. Brackets engage these tracks--by a lip that projects inwardly from the side wall of each bracket to capture the flange. The brackets can be slid by a user along the tracks and locked at any point along the slats by clamping plates inside the brackets. The clamping plates are forced against the slats as by screws in the tops of the brackets. One type of bracket carries an arch-shaped tie-down member and is also adapted for attachment of crossbars, spanning the outboard slats, but only at certain discrete points along the slats. Each tie-down member is fixed to its tie-down bracket below the inwardly projecting lip, or in any event at a point in the side wall, of the bracket. This configuration preserves clamping force when a strap or cord is tightly cinched from the bracket over luggage, resulting in very strong upward force on the tie-down member. If the tie-down members were attached to the tops of the brackets as is common in the prior art, the upward forces would reduce the force applied by screws or the like between the tops of the brackets and the clamping plates.
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REFERENCE TO PENDING PRIOR PATENT APPLICATION
This patent application claims benefit of pending prior U.S. Provisional Patent Application Ser. No. 60/939,615, filed May 22, 2007 by Tov Vestgaarden for PERCUTANEOUS SPINAL FACET FIXATION DEVICE FOR FACET FUSION, which patent application is hereby incorporated herein by reference.
FIELD OF THE INVENTION
This invention relates to surgical methods and apparatus in general, and more particularly to surgical methods and apparatus for fusing spinal facets.
BACKGROUND OF THE INVENTION
Disc herniation is a condition where a spinal disc bulges from between two vertebral bodies and impinges on adjacent nerves, thereby causing pain. The current standard of care for surgically treating disc herniation in patients who have chronic pain and who have (or are likely to develop) associated spinal instability is spinal fixation. Spinal fixation procedures are intended to relieve the impingement on the nerves by removing the portion of the disc and/or bone responsible for compressing the neural structures and destabilizing the spine. The excised disc or bone is replaced with one or more intervertebral implants, or spacers, placed between the adjacent vertebral bodies.
In some cases, the spinal fixation leaves the affected spinal segment unstable. In this case, the spinal facets (i.e., the bony fins extending upwardly and downwardly from the rear of each vertebral body) can misengage with one another. The misengagement of the spinal facets can cause substantial pain to the patient. Furthermore, when left untreated, such misengagement of the spinal facets can result in the degeneration of the cartilage located between opposing facet surfaces, ultimately resulting in osteoarthritis, which can in turn lead to worsening pain for the patient.
Thus, where the patient suffers from spinal instability, it can be helpful to stabilize the facet joints as well as the vertebral bodies. The facet joints are frequently stabilized by fusing the spinal facets in position relative to one another.
In addition to providing stability, fusing the spinal facets can also be beneficial in other situations as well. By way of example but not limitation, osteoarthritis (a condition involving the degeneration, or wearing away, of the cartilage at the end of bones) frequently occurs in the facet joints. The prescribed treatment for osteoarthritis disorders depends on the location, severity and duration of the disorder. In some cases, non-operative procedures (including bed rest, medication, lifestyle modifications, exercise, physical therapy, chiropractic care and steroid injections) may be satisfactory treatment. However, in other cases, surgical intervention may be necessary. In cases where surgical intervention is prescribed, spinal facet fusion may be desirable.
A minimally-invasive, percutaneous approach for fusing spinal facets was proposed by Stein et al. (“Stein”) in 1993. The Stein approach involved using a conical plug, made from cortical bone and disposed in a hole formed intermediate the spinal facet joint, to facilitate the fusing of opposing facet surfaces. However, the clinical success of this approach was limited. This is believed to be because the Stein approach did not adequately restrict facet motion. In particular, it is believed that movement of Stein's conical plug within its hole permitted unwanted facet movement to occur, thereby undermining facet fusion. Furthermore, the Stein approach also suffered from plug failure and plug migration.
Thus there is a need for a new and improved approach for effecting spinal facet fusion.
SUMMARY OF THE INVENTION
The present invention provides a novel method and apparatus for effecting spinal facet fusion. More particularly, the present invention comprises the provision and use of a novel spinal facet fusion implant for disposition between the opposing articular surfaces of a facet joint, whereby to immobilize the facet joint and facilitate fusion between the opposing facets.
More particularly, in one form of the present invention, there is provided a spinal facet fusion implant comprising:
an elongated body having a distal end, a proximal end and a longitudinal axis extending between the distal end and the proximal end, the elongated body having a cross-sectional profile characterized by a primary axis and a secondary axis; and
at least one stabilizer extending radially outwardly from the elongated body in the secondary axis;
wherein the elongated body has a length along the primary axis which is less than the combined width of the spinal facets making up a facet joint;
and further wherein the at least one stabilizer has a width which is sized to make a press fit into the gap between the spinal facets making up a facet joint.
In another form of the present invention, there is provided a method for fusing a spinal facet joint, the method comprising the steps of:
providing a spinal facet fusion implant comprising:
an elongated body having a distal end, a proximal end and a longitudinal axis extending between the distal end and the proximal end, the elongated body having a cross-sectional profile characterized by a primary axis and a secondary axis; and at least one stabilizer extending radially outwardly from the elongated body in the secondary axis; wherein the elongated body has a length along the primary axis which is less than the combined width of the spinal facets making up a facet joint; and further wherein the at least one stabilizer has a width which is sized to make a press fit into the gap between the spinal facets making up a facet joint;
deploying the spinal facet fusion implant in the facet joint so that the elongated body is simultaneously positioned within both of the facets of the facet joint and the at least one stabilizer is positioned within the gap between the spinal facets; and
maintaining the spinal facet fusion implant in this position while fusion occurs.
In another form of the present invention, there is provided a spinal facet fusion implant comprising:
an elongated body having a distal end, a proximal end and a longitudinal axis extending between the distal end and the proximal end, the elongated body having a cross-sectional profile which is characterized by a primary axis and a secondary axis;
wherein the elongated body has a length along the primary axis which is less than the combined width of the spinal facets making up a facet joint;
and further wherein the cross-sectional profile is non-circular.
In yet another form of the present invention, there is provided a method for fusing a spinal facet joint, the method comprising the steps of:
providing a spinal facet fusion implant comprising:
an elongated body having a distal end, a proximal end and a longitudinal axis extending between the distal end and the proximal end, the elongated body having a cross-sectional profile which is characterized by a primary axis and a secondary axis; wherein the elongated body has a length along the primary axis which is less than the combined width of the spinal facets making up a facet joint; and further wherein the cross-sectional profile is non-circular;
deploying the spinal facet fusion implant in the facet joint so that the elongated body is simultaneously positioned within both of the facets of the facet joint; and
maintaining the spinal facet fusion implant in this position while fusion occurs.
In still another form of the present invention, there is provided a joint fusion implant comprising:
an elongated body having a distal end, a proximal end and a longitudinal axis extending between the distal end and the proximal end, the elongated body having a cross-sectional profile characterized by a primary axis and a secondary axis; and
at least one stabilizer extending radially outwardly from the elongated body in the secondary axis;
wherein the elongated body has a length along the primary axis which is less than the combined width of the bones making up the joint;
and further wherein the at least one stabilizer has a width which is sized to make a press fit into the gap between the bones making up the joint.
In an additional form of the present invention, there is provided a method for fusing a joint, the method comprising the steps of:
providing a fusion implant comprising:
an elongated body having a distal end, a proximal end and a longitudinal axis extending between the distal end and the proximal end, the elongated body having a cross-sectional profile characterized by a primary axis and a secondary axis; and at least one stabilizer extending radially outwardly from the elongated body in the secondary axis; wherein the elongated body has a length along the primary axis which is less than the combined width of the bones making up the joint; and further wherein the at least one stabilizer has a width which is sized to make a press fit into the gap between the bones making up the joint;
deploying the fusion implant in the joint so that the elongated body is simultaneously positioned within both of the bones of the joint and the at least one stabilizer is positioned within the gap between the bones; and
maintaining the fusion implant in this position while fusion occurs.
BRIEF DESCRIPTION OF THE DRAWINGS
These and other objects and features of the present invention will be more fully disclosed or rendered obvious by the following detailed description of the preferred embodiments of the invention, which is to be considered together with the accompanying drawings wherein like numbers refer to like parts, and further wherein:
FIGS. 1-3 illustrate fusion implants formed in accordance with the present invention;
FIGS. 4 and 5 illustrate a fusion implant being installed in a facet joint;
FIGS. 6-12 illustrate instrumentation which may be used to install a solid fusion implant in a facet joint;
FIGS. 13-26 illustrate a preferred method for installing a solid fusion implant in the facet joint;
FIGS. 27-28 illustrate instrumentation which may be used to install a hollow fusion implant in a facet joint; and
FIGS. 29-74 illustrate alternative fusion implants formed in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
In General
Looking first at FIG. 1 , there is shown a novel spinal facet fusion implant 5 formed in accordance with the present invention. Fusion implant 5 generally comprises a body 10 and at least one stabilizer 15 .
Body 10 comprises an elongated element having structural integrity. Preferably the distal end of body 10 (and the distal end of stabilizer 15 as well) is chamfered as shown at 20 to facilitate insertion of fusion implant 5 into the facet joint, as will hereinafter be discussed. Preferably, and as seen in FIG. 1 , body 10 has a rounded rectangular cross-section, or an ovoid cross-section, a laterally-extended cross-section, or some other non-round cross-section, so as to inhibit rotation of body 10 about a longitudinal center axis. If desired, body 10 may include a plurality of barbs (i.e., forward biting teeth) 25 extending outwardly therefrom. Barbs 25 are designed to permit body 10 to be inserted into the facet joint and to impede retraction of body 10 out of the facet joint.
The at least one stabilizer 15 is intended to be received in the gap located between the opposing facet surfaces, whereby to prevent rotation of fusion implant 5 within the facet joint. In one preferred form of the present invention, two stabilizers 15 are provided, one disposed along the upper surface of body 10 and one disposed along the lower surface of body 10 . Stabilizers 15 preferably have a width just slightly larger than the gap between the opposing articular surfaces of a facet joint, so that the stabilizers can make a snug fit therebetween.
If desired, and looking now at FIG. 2 , fusion implant 5 may also be configured so that its body 10 lacks barbs 25 on its outer surface.
Alternatively, if desired, and looking now at FIG. 3 , fusion implant 5 may comprise a hollow body 10 having an internal cavity 30 . Hollow body 10 may also have a plurality of openings 35 extending through the side wall of body 10 and communicating with cavity 30 . Internal cavity 30 and openings 35 can facilitate facet fusion by permitting bone ingrowth into and/or through fusion implant 5 .
Fusion implant 5 is intended to be inserted into a facet joint using a posterior approach. The posterior approach is familiar to spine surgeons, thereby providing an increased level of comfort for the surgeon, and also minimizing the possibility of damage to the spinal cord during fusion implant insertion.
In use, and looking now at FIG. 4 , an instrument is first used to determine the vertical plane 40 of the facet joint. Identifying the vertical plane of the facet joint is important, since this is used to identify the proper position for a cavity 45 which is to be formed in the facet joint to receive the fusion implant.
To this respect it should be appreciated that at least one of the instruments comprises a directional feature which is used to maintain the alignment of the instrumentation with the vertical plane of the facet joint. By way of example but not limitation, a directional cannula may comprise a flat portion and the remaining instruments may comprise a flat portion on an opposite portion of the instrument so that the instruments may only be inserted through the cannula at 0 degrees and/or 180 degrees.
After the proper position for cavity 45 has been identified, a drill (or reamer, punch, dremel, router, burr, etc.) is used to form the cavity 45 in the facet joint. Cavity 45 is formed across vertical plane 40 so that substantially one-half of cavity 45 is formed in a first facet 50 , and substantially one-half is formed in its opposing facet 55 .
After cavity 45 has been formed in (or, perhaps more literally, across) the facet joint, fusion implant 5 is inserted into cavity 45 . See FIG. 5 . More particularly, fusion implant 5 is inserted into cavity 45 so that (i) body 10 spans the gap between opposing facets 50 , 55 , and (ii) stabilizers 15 extend between the opposing facet surfaces. Preferably, fusion implant 5 is slightly oversized relative to cavity 45 so as to create a press fit. Fusion implant 5 provides the stability and strength needed to immobilize the facet joint while fusion occurs. Due to the positioning of stabilizers 15 between the opposing facet surfaces, and due to the non-circular cross-section of body 10 , fusion implant 5 will be held against rotation within cavity 45 , which will in turn hold facets 50 , 55 stable relative to one another.
It should be appreciated that where the hollow fusion implant 10 of FIG. 3 is used, and where the implant is formed out of a sufficiently strong and rigid material, cavity 45 need not be pre-formed in the opposing facets. In this case, the hollow fusion implant can be simply tapped into place, in much the same manner that a punch is used.
Thus it will be seen that the present invention provides a new and improved fusion implant for facilitating facet fusion. This new fusion implant is able to withstand greater forces, prohibit motion in all directions and drastically reduce the risk of implant failure. The new fusion implant also eliminates the possibility of slippage during spinal motion, greatly improves facet stability and promotes better facet fusion.
It should be appreciated that the new fusion implant combines two unique “shapes” in one implant (i.e., the shape of body 10 and the shape of stabilizer 15 ) in order to limit motion in a multi-directional joint. More particularly, the shape of body 10 limits motion (e.g., in flexion/extension for the lumbar facets and in axial rotation for the cervical facets), while the shape of stabilizer 15 (i.e., the “keel”) rests between two bony structures (i.e., in the gap of the facet joint) and limits lateral bending. This construction eliminates the possibility of eccentric forces inducing motion in the facet joint.
Furthermore, it has been found that while the present invention effectively stabilizes the joint, it still allows the “micro motion” which is required for the fusion process to begin.
It should be appreciated that the new fusion implant may be manufactured in a wide range of different sizes in order to accommodate any size of facet joint. Furthermore, the scale and aspect ratio of body 10 , stabilizers 15 , barbs 25 , openings 35 , etc. may all be varied without departing from the scope of the present invention. Additionally, the new fusion implant may be constructed out of any substantially biocompatible material which has properties consistent with the present invention including, but not limited to, allograft, autograft, synthetic bone, simulated bone material, biocomposites, ceramics, PEEK, stainless steel and titanium. Thus, the present invention permits the surgeon to select a fusion implant having the appropriate size and composition for a given facet fusion.
Detailed Surgical Technique
Solid Fusion Implant
A preferred surgical technique for utilizing a solid fusion implant 5 will now be described. The preferred surgical technique preferably uses a guide pin 100 ( FIG. 6 ) a facet distractor 105 ( FIG. 7 ), a directional cannula 110 ( FIG. 8 ), a drill guide 115 ( FIG. 9 ), a cavity cutter 117 ( FIG. 9A ), an implant loading block 120 ( FIG. 10 ), an implant holder 125 ( FIG. 11 ) and an implant tamp 130 ( FIG. 12 ).
First, the facet joint is localized indirectly by fluoroscopy, or directly by visualization during an open procedure. Next, a guide pin 100 ( FIG. 13 ) is inserted into the gap between the opposing facet surfaces. The position of guide pin 100 is verified by viewing the coronal and sagittal planes. Then guide pin 100 is lightly tapped so as to insert the guide pin approximately 5 mm into the facet joint, along vertical plane 40 . In this respect it will be appreciated that the inferior facet is curved medially and will help prevent the guide pin from damaging the nerve structures.
Next, a cannulated facet distractor 105 is slid over guide pin 100 ( FIG. 14 ) so that it is aligned with the vertical plane of the facet joint. Then facet distractor 105 is lightly tapped into the facet joint, along vertical plane 40 ( FIG. 15 ).
Next, a directional cannula 110 is placed over facet distractor 105 ( FIG. 16 ). Then the tip of directional cannula 110 is pushed into the facet joint ( FIG. 17 ). Once the tip of directional cannula 110 has entered the facet joint, the directional cannula is lightly tapped so as to seat the cannula in the facet joint. This aligns directional cannula 110 with the vertical plane of the facet joint. After verifying that directional cannula 110 has been inserted all the way into the facet joint and is stabilized in the joint, facet distractor 105 is removed ( FIG. 18 ).
Next, a drill guide 115 is inserted into directional cannula 110 ( FIG. 19 ). Drill guide 115 is advanced within directional cannula 110 until a drill guide stop is resting on directional cannula 110 . Then, with drill guide 115 in place, irrigation (e.g., a few drops of saline) is placed into drill guide. Next, a drill bit 135 is used to drill a cavity in the inferior facet ( FIG. 20 ). This is done by drilling until drill bit 135 reaches the mechanical stop on drill guide 115 ( FIG. 21 ). Then drill guide 115 and drill bit 135 are pulled out of directional cannula 110 , drill guide 115 is rotated 180 degrees, and then drill guide 115 is reinserted into directional cannula 110 in order to drill the superior facet. With drill guide 115 in place, irrigation (e.g., a few drops of saline) is placed into drill guide 115 , and then drill bit 135 is used to drill a cavity in the superior facet ( FIG. 22 ). Again, drilling occurs until drill bit 135 reaches the mechanical stop on drill guide 115 . Then drill bit 135 is removed ( FIG. 23 ).
A cavity cutter 117 is then used to make an opening having the perfect shape for fusion implant 5 .
Using implant loading block 120 shown in FIG. 10 , fusion implant 5 is then inserted into implant holder 125 . Then implant holder 125 , with fusion implant 5 in place, is placed into directional cannula 110 ( FIG. 24 ). Next, implant holder 125 is lightly tapped so as to insert fusion implant 5 into the cavity created in the facet joint ( FIG. 25 ). Once the implant has been positioned in the cavity created in the facet joint, implant tamp 130 is inserted into implant holder 125 . Next, implant tamp 130 is lightly tapped so as to drive the implant into the cavity created in the facet joint ( FIG. 26 ). The implant is preferably countersunk 1-2 mm into the facet joint.
Then the foregoing steps are repeated for the contralateral facet joint.
Finally, implant tamp 130 , implant holder 125 and directional cannula 110 are removed from the surgical site and the incision is closed.
Detailed Surgical Technique
Hollow Fusion Implant
A preferred surgical technique for utilizing a hollow fusion implant 5 will now be described. The preferred surgical technique preferably uses guide pin 100 ( FIG. 6 ), facet distractor 105 ( FIG. 7 ), and an implant punch 140 ( FIG. 27 ).
First, the facet joint is localized indirectly by fluoroscopy or directly by visualization during an open procedure. Next, guide pin 100 is inserted in the gap between the opposing facet surfaces. The position of guide pin 100 is verified by viewing the coronal and sagittal planes. Then guide pin 100 is lightly tapped so as to insert guide pin 100 approximately 5 mm into the facet joint, along the vertical plane of the facet joint. In this respect it will be appreciated that inasmuch as the inferior facet curves medially, this will help prevent the guide pin from damaging the nerve structures.
Then the cannulated facet distractor 105 is slid over guide pin 100 so that it is aligned with the vertical plane of the facet joint. Facet distractor 105 is lightly tapped into the facet joint, along the vertical plane of the facet joint.
Next, implant punch 140 ( FIG. 27 ), with a hollow fusion implant 5 mounted thereto ( FIG. 28 ) is pushed (or hammered or otherwise advanced) downwards so as to drive hollow fusion implant 5 into the facet joint.
Finally, implant punch 140 and guide pin 100 are removed, leaving hollow fusion implant 5 in the facet joint, and the incision is closed.
Alternative Constructions
The configuration of fusion implant 5 may be varied without departing from the scope of the present invention.
In one configuration, and looking now at FIGS. 29-31 , there is provided a fusion implant 5 comprising a rounded rectangular elongated body and two stabilizers. Preferably, the body comprises a groove extending circumferentially around the exterior surface of the body.
Looking next at FIGS. 32-34 , there is shown a fusion implant 5 comprising a rounded elongated body, which is similar to the embodiment shown in FIGS. 29-31 , however, the elongated body has a different aspect ratio and the elongated body is formed with a substantially smooth outer surface (e.g., without grooves or barbs).
FIGS. 35-37 illustrate a fusion implant 5 having an elongated body which is similar to the elongated body shown in FIGS. 29-31 , but without a stabilizer and with an elongated body which is formed with a substantially smooth outer surface (e.g., without grooves or barbs).
FIGS. 38-40 illustrate a fusion implant 5 having an elongated body with a smaller radius on the rounded edges than the embodiment shown in FIGS. 29-31 . Furthermore, the elongated body is formed with a smooth outer surface.
FIGS. 41-43 illustrate a fusion implant 5 which is similar to the implant of FIGS. 29-31 , but with the main body having a substantially circular configuration.
FIGS. 44-47 illustrate a fusion implant 5 which is similar to the implant of FIGS. 29-31 and further comprises a through-hole extending through the elongated body. The through-hole allows a bone growth promoter to be packed through and across the width of the fusion implant, thereby enabling rapid fusion through the implant.
FIGS. 48-50 illustrate a fusion implant 5 which is similar to the implant of FIGS. 29-31 . However, in this embodiment, the grooves are replaced with barbs (i.e., forward biting teeth) extending around the surface of the body.
FIGS. 51-54 illustrate a fusion implant 5 which is similar to the embodiment shown in FIGS. 48-50 , however, the fusion implant comprises a hollow body having an internal cavity and plurality of openings extending through the side wall of the body and communicating with the cavity.
FIGS. 55-57 illustrate a fusion implant 5 which is similar to the embodiment shown in FIGS. 29-31 , however, the fusion implant comprises a hollow body having an internal cavity and plurality of openings extending through the side wall of the body and communicating with the cavity.
FIGS. 58-60 illustrate a fusion implant 5 which is similar to the embodiment shown in FIGS. 29-31 and further comprises a hole for attaching the implant to the facet joint. The attachment may be effected by K-Wire, suture, staple, screw or other fixation device.
FIGS. 61-64 illustrate a fusion implant 5 which is similar to the embodiment shown in FIGS. 29-31 and further comprises a hole for attaching the implant to the facet joint. The attachment may be effected by K-Wire, suture, staple, screw or other fixation device. Preferably, a screw is used to attach the implant to the facet joint.
FIGS. 65-68 illustrate a fusion implant 5 which is similar to the embodiment shown in FIGS. 29-31 and further comprises a hole for attaching the implant to the facet joint. The attachment may be effected by an integrated screw. Like FIGS. 29-31 , this embodiment may also comprise grooves.
FIGS. 69-71 illustrate a fusion implant 5 which is similar to the embodiment shown in FIGS. 29-31 and further comprises rectangular, sharp spikes for attaching the implant to the facet joint.
FIGS. 72-74 illustrate a fusion implant 5 which is similar to the embodiment shown in FIGS. 29-31 and further comprises round, sharp spikes for attaching the implant to the facet joint.
ADVANTAGES OF THE INVENTION
Numerous advantages are achieved by the present invention. Among other things, the present invention provides a fast, simple, minimally-invasive and easily reproduced approach for effecting facet fusion.
Applications to Joints Other than Facet Joints
While fusion implant 5 has been discussed above in the context of fusing a facet joint, it should also be appreciated that fusion implant 5 may be used to stabilize and fuse any joint having anatomy similar to the facet joint, i.e., a pair of opposing bony surfaces defining a gap therebetween, with the stabilizer of the fusion implant being sized to be positioned within the gap. By way of example but not limitation, the fusion implant may be used in small joints such as the fingers, toes, etc.
MODIFICATIONS OF THE PREFERRED EMBODIMENTS
It should be understood that many additional changes in the details, materials, steps and arrangements of parts, which have been herein described and illustrated in order to explain the nature of the present invention, may be made by those skilled in the art while still remaining within the principles and scope of the invention.
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A spinal facet fusion implant comprising:
an elongated body having a distal end, a proximal end and a longitudinal axis extending between the distal end and the proximal end, the elongated body having a cross-sectional profile characterized by a primary axis and a secondary axis; and at least one stabilizer extending radially outwardly from the elongated body in the secondary axis; wherein the elongated body has a length along the primary axis which is less than the combined width of the spinal facets making up a facet joint; and further wherein the at least one stabilizer has a width which is sized to make a press fit into the gap between the spinal facets making up a facet joint.
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FIELD OF THE INVENTION
[0001] This invention relates to compounds, formulations, drinks, foodstuffs, methods and therapeutic uses involving, containing, comprising, including and/or for preparing certain isoflavone compounds and analogues thereof. In particular, the invention relates to 6-hydroxy substituted isoflavones, derivatives thereof and medicaments involving same.
BACKGROUND OF THE INVENTION
[0002] Naturally-occurring plant isoflavones are known to possess a wide range of fundamental biological effects on human cells including anti-oxidation and the up-regulation and down-regulation of a wide variety of enzymes and signal transduction mechanisms. Mitotic arrest and cytotoxicity of human cancer cells, increased capillary permeability, increased cellular adhesion, increased response of vascular smooth muscle cells to vaso-relaxants, and agonism of estrogen receptors, are just a few examples of the responses of animal cells to the biological effects of naturally-occurring isoflavonoids.
[0003] A range of therapeutic benefits as a result of these biological outcomes have been identified including the treatment and prevention of pre-menopausal symptoms such as pre-menstrual syndrome, endometriosis, uterine fibroids, hyperlipidaemia, cardiovascular disease, menopausal symptoms such as osteoporosis and senile dementia, alcoholism, benign prostatic hypertrophy, and cancers such as prostate, breast and large bowel carcinomas [see WO 93/23069; WO 96/10341; U.S. Pat. No. 5,424,331; JP 62-106017; JP 62-106016; U.S. Pat. No. 5,516,528; JP 62-106016A2; JP 62-106017A2; JP 61-246124; WO 98/50026; WO 99/43335; WO 00/49009; WO 00/644,438; WO 99/48496].
[0004] While over 700 different naturally occurring isoflavones are described, only a few are confirmed as having potential therapeutic benefits in animals including humans. These include daidzein, genistein, formononetin, biochanin and glycitein. These and all naturally occurring isoflavones are found in nature as the monomeric form either in a free state, or, more likely, bound to a carbohydrate moiety (glycoside). The isoflavone has to be separated from this moiety before it becomes biologically active.
[0005] A number of compounds with a structure related to naturally occurring plant isoflavones are also described as having biological properties with potential therapeutic benefit to animals including humans. These include compounds that are naturally occurring metabolites of plant isoflavones produced by bacterial fermentation by gut flora and embrace compounds such as equol and 0-desmethylangolensin [WO 93/23069; WO 98/08503; WO 01/17986; WO 00/66576]. Also included in this group is the synthetic isoflavonoid ipriflavone, which is developed for the treatment of postmenopausal osteoporosis [WO 91/14429] and a wide range of synthetic isoflavonoid analogues [WO 98/08503].
[0006] Despite the considerable research and accumulated knowledge in relation to isoflavonoid compounds and derivatives thereof, the full ambit of therapeutically useful isoflavonoid compounds and their activities is yet to be realised. Moreover, there is a continual need for new, improved or at least alternative active agents for the treatment, prophylaxis, amelioration, defence against and/or prevention of various diseases and disorders.
[0007] A requirement accordingly exists for new generation compounds that exhibit important pharmacological effects for use as prophylactics and in therapy.
SUMMARY OF THE INVENTION
[0008] According to an aspect of this invention there is provided isoflavone compounds and analogues thereof of the general formula (I):
in which
R 1 and R 2 are independently hydrogen, hydroxy, OR 9 , OC(O)R 10 , OS(O)R 10 , CHO, C(O)R 10 , COOH, CO 2 R 10 , CONR 3 R 4 , alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino, dialkylamino, nitro or halo, and Z O is hydroxy, or R 2 is as previously defined, and R 1 and Z O taken together with the carbon atoms to which they are attached form a five-membered ring selected from
R 1 is as previously defined, and R 2 and Z O taken together with the carbon atoms to which they are attached form a five-membered ring selected from
and
W is R 1 , A is hydrogen, hydroxy, NR 3 R 4 or thio, and B is selected from
W is R 1 , and A and B taken together with the carbon atoms to which they are attached form a six-membered ring selected from
W, A and B taken together with the groups to which they are associated comprise
W and A taken together with the groups to which they are associated comprise
and B is
wherein
R 3 is hydrogen, alkyl, aryl, arylalkyl, an amino acid, C(O)R 11 where R 11 is hydrogen alkyl, aryl, arylalkyl or an amino acid, or CO 2 R 12 where R 12 is hydrogen, alkyl, haloalkyl, aryl or arylalkyl, R 4 is hydrogen, alkyl or aryl, or R 3 and R 4 taken together with the nitrogen to which they are attached comprise pyrrolidinyl or piperidinyl, R 5 is hydrogen, C(O)R 11 where R 11 is as previously defined, or CO 2 R 12 where R 12 is as previously defined, R 6 is hydrogen, hydroxy, alkyl, aryl, amino, thio, NR 3 R 4 , COR 11 where R 11 is as previously defined, CO 2 R 12 where R 12 is as previously defined or CONR 3 R 4 , R 7 is hydrogen, C(O)R 11 where R 11 is as previously defined, alkyl, haloalkyl, aryl, arylalkyl or Si(R 13 ) 3 where each R 13 is independently hydrogen, alkyl or aryl, R 8 is hydrogen, hydroxy, alkoxy or alkyl, R 9 is alkyl, haloalkyl, aryl, arylalkyl, C(O)R 11 where R 11 is as previously defined, or Si(R 13 ) 3 where R 13 is as previously defined, R 10 is hydrogen, alkyl, haloalkyl, amino, aryl, arylalkyl, an amino acid, alkylamino or dialkylamino,
the drawing “ ” represents either a single bond or a double bond,
T is independently hydrogen, alkyl or aryl, X is O, NR 4 or S, and Y is
wherein
R 14 , R 15 and R 16 are independently hydrogen, hydroxy, OR 9 , OC(O)R 10 , OS(O)R 10 , CHO, C(O)R 10 , COOH, CO 2 R 10 , CONR 3 R 4 , alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino, dialkylamino, nitro or halo, or any two of R 14 , R 15 and R 16 are fused together to form a cyclic alkyl, aromatic or heteroaromatic structure,
with the proviso that
when B is
Y is phenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 3-hydroxyphenyl, 3-methoxyphenyl, 3-hydroxy-4-methoxyphenyl, 4-hydroxy-3-methoxyphenyl, 3,4-dihydroxyphenyl or 3,4-dimethoxyphenyl, and W and R 2 are hydrogen,
then
R 1 is not hydrogen, hydroxy or methoxy, or R 1 and Z O together with the carbon atoms to which they are attached are not cyclic boronates, carbonates, acetyls or ketals, and when A and B taken together with the carbon atoms to which they are attached form a six-membered ring selected from
X is O, Y is phenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 3-hydroxyphenyl, 3-methoxyphenyl, 3-hydroxy-4-methoxyphenyl, 4-hydroxy-3-methoxyphenyl, 3,4-dihydroxyphenyl or 3,4-dimethoxyphenyl, and W and R 2 are hydrogen,
then
R 1 is not hydrogen, hydroxy or methoxy, or R 1 and Z O together with the carbon atoms to which they are attached are not a cyclic boronate, carbonate, acetyl or ketal,
or a pharmaceutically acceptable salt or prodrug thereof.
[0049] It has surprisingly been found by the inventors that the isoflavonoid derivatives of the general formula (I) have particular utility and effectiveness in the treatment, prophylaxis, amelioration defence against, and/or prevention of one of more of the following diseases and disorders (for convenience hereinafter referred to as the “therapeutic indications”):
(a) all forms of cancer (pre-malignant, benign and malignant) in all tissues of the body including breast cancer; uterine cancer; ovarian cancer; testicular cancer; large bowel cancer; endometrial cancer; prostatic cancer; uterine cancer. In this regard, the compounds may be used as the sole form of anti-cancer therapy or in combination with other forms of anti-cancer therapy including but not limited to radiotherapy and chemotherapy; (b) diseases and disorders associated with inflammatory reactions of an abnormal or prolonged nature in any of the body's tissues including but not limited to rheumatoid arthritis, tendonitis, inflammatory bowel disease, ulcerative colitis, Crohn's Disease, sclerosing cholangitis; (c) papulonodular skin lesions including but not limited to sarcoidosis, angiosarcoma, Kaposi's sarcome, Fabry's Disease (d) papulosquamous skin lesions including but not limited to psoriasis, Bowen's Disease, and Reiter's Disease; (e) actinic damage characterized by degenerative changes in the skin including but not limited to solar keratosis, photosensitivity diseases, and wrinkling; (f) diseases and disorders associated with abnormal angiogenesis affecting any tissue within the body including but not limited to hemangiomas and telangiectasia; (g) proliferative disorders of bone marrow including but not limited to megaloblastic disease, myelodysplastic syndromes, polycythemia vera, thrombocytosis and myelofibrosis; (h) autoimmune disease characterized by abnormal immunological responses including but not limited to multiple sclerosis, Type 1 diabetes, systemic lupus erythematosis, and biliary cirrhosis; (i) neurodegenerative diseases and disorders characterised by degenerative changes in the structure of the neurological system including but not limited to Parkinson's Disease, Alzheimer's Disease, muscular dystrophy, Lou-Gehrig Disease, motorneurone disease; (j) diseases and disorders associated with degenerative changes within the walls of blood vessels including but not limited to atherosclerosis, stenosis, restenosis, atheroma, coronary artery disease, stroke, myocardial infarction, hypertensive vascular disease, malignant hypertension, thromboangiitis obliterans, fibromuscular dysplasia; (k) diseases and disorders associated with abnormal immunological responses including but limited to dermatomyositis and scleroderma; (l) diseases and disorders associated with degenerative changes within the eye including but not limited to cataracts, macular degeneration, retinal atrophy.
[0062] In particular the isoflavonoid derivatives also surprisingly have been found to have a potent effect on the production and function of reproductive hormones such as estrogens and androgens. As a result of this, these compounds may be used in the treatment and prevention of one or more of the following disorders and diseases:
(a) conditions in women associated with abnormal estrogen/androgen balance including but not limited to cyclical mastalgia, acne, dysmenorrhoea, uterine fibroids, endometriosis, ovarian cysts, premenstrual syndrome, acute menopause symptoms, osteoporosis, senile dementia, infertility; and (b) conditions in men associated with abnormal estrogen/androgen balance including but not limited to benign prostatic hypertrophy, infertility, gynecomastia, alopecia hereditaria and various other forms of baldness.
[0065] Thus, according to a second aspect of the present invention there is provided a method for the treatment, prophylaxis or amelioration of a disease or disorder which method includes the step of administering a therapeutically effective amount of one or more compounds of formula (I) to a subject.
[0066] According to a third aspect of the present invention there is provided the use of one or more compounds of formula (I) in the manufacture of a medicament for the treatment of disease or disorder.
[0067] According to a forth aspect of the present invention there is provided the use of one or more compounds selected from formula (I) for the treatment, amelioration, defence against, prophylaxis and/or prevention of abnormal estrogen/androgen balance or a condition resulting from said abnormal balance in men or women.
[0068] According to a fifth aspect of the present invention there is provided the use of one or more compounds selected from formula (I) in the manufacture of a medicament for the treatment, amelioration, defence against, prophylaxis and/or prevention of abnormal estrogen/androgen balance or a condition resulting from said abnormal balance in men or women.
[0069] According to a sixth aspect of the present invention there is provided an agent for the treatment, prophylaxis or amelioration of a disease or disorder which agent comprises one or more compounds of formula (I).
[0070] According to a seventh aspect of the present invention there is provided a pharmaceutical composition which comprises one or more compounds of formula (I) in association with one or more pharmaceutical carriers, excipients, auxiliaries and/or diluents.
[0071] According to an eighth aspect of the present invention there is provided a drink or food-stuff, which contains one or more compounds of formula (I).
[0072] According to a ninth aspect of the present invention there is provided a microbial culture or a food-stuff containing one or more microbial strains which microorganisms produce one or more compounds of formula (I).
[0073] According to an tenth aspect of the present invention there is provided one or more microorganisms which produce one or more compounds of formula (I). Preferably the microorganism is a purified culture, which may be admixed and/or administered with one or more other cultures which product compounds of formula (I).
[0074] These and other aspects of the invention will become evident from the description and claims which follow.
[0075] Throughout this specification and the claims which follow, unless the text requires otherwise, the word “comprise”, and variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.
DETAILED DESCRIPTION OF THE INVENTION
[0076] The term “isoflavone” as used herein is to be taken broadly to include ring-fused benzopyran molecules having a pendent phenyl group from the pyran ring based on a 1,2-diphenylpropane system and to ring-opened benzopyran molecules where the pyran oxygen may also be a heteratom selected from nitrogen and sulfur. Thus, the classes of compounds generally referred to as isoflavones, isoflavenes, isoflavans, isoflavanones, isoflavanols and the like are generically referred to herein as isoflavones, isoflavone derivatives or isoflavonoid molecules, compounds or derivatives.
[0077] The term “alkyl” is taken to include straight chain, branched chain and cyclic (in the case of 5 carbons or greater) saturated alkyl groups of 1 to 10 carbon atoms, preferably from 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, tertiary butyl, pentyl, cyclopentyl, and the like. The alkyl group is more preferably methyl, ethyl, propyl or isopropyl. The alkyl group may optionally be substituted by one or more of fluorine, chlorine, bromine, iodine, carboxyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylamino-carbonyl, di-(C 1 -C 4 -alkyl)-amino-carbonyl, hydroxyl, C 1 -C 4 -alkoxy, formyloxy, C 1 -C 4 -alkyl-carbonyloxy, C 1 -C 4 -alkylthio, C 3 -C 6 -cycloalkyl or phenyl.
[0078] The term “alkenyl” is taken to include straight chain, branched chain and cyclic (in the case of 5 carbons or greater) hydrocarbons of 2 to 10 carbon atoms, preferably 2 to 6 carbon atoms, with at lease one double bond such as ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 2-methyl-1-peopenyl, 2-methyl-2-propenyl, and the like. The alkenyl group is more preferably ethenyl, 1-propenyl or 2-propenyl. The alkenyl groups may optionally be substituted by one or more of fluorine, chlorine, bromine, iodine, carboxyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylamino-carbonyl, di-(C 1 -C 4 -alkyl)-amino-carbonyl, hydroxyl, C 1 -C 4 -alkoxy, formyloxy, C 1 -C 4 -alkyl-carbonyloxy, C 1 -C 4 -alkylthio, C 3 -C 6 -cycloalkyl or phenyl.
[0079] The term “alkynyl” is taken to include both straight chain and branched chain hydrocarbons of 2 to 10 carbon atoms, preferably 2 to 6 carbon atoms, with at least one triple bond such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, and the like. The alkynyl group is more preferably ethynyl, 1-propynyl or 2-propynyl. The alkynyl group may optionally be substituted by one or more of fluorine, chlorine, bromine, iodine, carboxyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylamino-carbonyl, di-(C 1 -C 4 -alkyl)-amino-carbonyl, hydroxyl, C 1 -C 4 -alkoxy, formyloxy, C 1 -C 4 -alkyl-carbonyloxy, C 1 -C 4 -alkylthio, C 3 -C 6 -cycloalkyl or phenyl.
[0080] The term “aryl” is taken to include phenyl, biphenyl and naphthyl and may be optionally substituted by one or more C 1 -C 4 -alkyl, hydroxy, C 1 -C 4 -alkoxy, carbonyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylcarbonyloxy or halo.
[0081] The term “heteroaryl” is taken to include five-membered and six-membered rings which include at least one oxygen, sulfur or nitrogen in the ring, which rings may be optionally fused to other aryl or heteroaryl rings including but not limited to furyl, pyridyl, pyrimidyl, thienyl, imidazolyl, tetrazolyl, pyrazinyl, benzofuranyl, benzothiophenyl, quinolyl, isopuinolyl, purinyl, morpholinyl, oxazolyl, thiazolyl, pyrrolyl, xanthinyl, purine, thymine, cytosine, uracil, and isoxazolyl. The heteroaromatic group can be optionally substituted by one or more of fluorine, chlorine, bromine, iodine, carboxyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylamino-carbonyl, di-(C 1 -C 4 -alkyl)-amino-carbonyl, hydroxyl, C 1 -C 4 -alkoxy, formyloxy, C 1 -C 4 -alkyl-carbonyloxy, C 1 -C 4 -alkylthio, C 3 -C 6 -cycloalkyl or phenyl. The heteroaromatic can be partially or totally hydrogenated as desired.
[0082] The term “halo” is taken to include fluoro, chloro, bromo and iodo, preferably fluoro and chloro, more preferably fluoro. Reference to for example “haloalkyl” will include monohalogenated, dihalogenated and up to perhalogenated alkyl groups. Preferred haloalkyl groups are trifluoromethyl and pentafluoroethyl.
[0083] The term “pharmaceutically acceptable salt” refers to an organic or inorganic moiety that carries a charge and that can be administered in association with a pharmaceutical agent, for example, as a counter-cation or counter-anion in a salt. Pharmaceutically acceptable cations are known to those of skilled in the art, and include but are not limited to sodium, potassium, calcium, zinc and quaternary amine. Pharmaceutically acceptable anions are known to those of skill in the art, and include but are not limited to chloride, acetate, citrate, bicarbonate and carbonate.
[0084] The term “pharmaceutically acceptable derivative” or “prodrug” refers to a derivative of the active compound that upon administration to the recipient is capable of providing directly or indirectly, the parent compound or metabolite, or that exhibits activity itself.
[0085] As used herein, the terms “treatment”, “prophylaxis” or “prevention”, “amelioration” and the like are to be considered in their broadest context. In particular, the term “treatment” does not necessarily imply that an animal is treated until total recovery. Accordingly, “treatment” includes amelioration of the symptoms or severity of a particular condition or preventing or otherwise reducing the risk of developing a particular condition.
[0086] The invention in particular relates to compounds of the general formulae (II)-(VIII):
in which
R 1 , R 2 , R 5 , R 6 , R 14 , R 15 , W and Z O are as defined above
more preferably
R 1 , R 2 , R 14 , R 15 , and W are independently hydrogen, hydroxy, OR 9 , OC(O)R 10 , C(O)R 10 , COOH, CO 2 R 10 , alkyl, haloalkyl, arylalkyl, aryl, thio, alkylthio, amino, alkylamino, dialkylamino, nitro or halo, Z O is hydroxy, R 5 is hydrogen, C(O)R 11 where R 11 is hydrogen, alkyl, aryl, or an amino acid, or CO 2 R 12 where R 12 is hydrogen, alkyl or aryl, R 6 is hydrogen, hydroxy, alkyl, aryl, COR 11 where R 11 is as previously defined, or CO 2 R 12 where R 12 is as previously defined, R 9 is alkyl, haloalkyl, arylalkyl, or C(O)R 11 where R 11 is as previously defined, and R 10 is hydrogen, alkyl, amino, aryl, an amino acid, alkylamino or dialkylamino,
more preferably
R 1 and R 14 are independently hydroxy, OR 9 , OC(O)R 10 or halo, R 2 , R 15 , and W are independently hydrogen, hydroxy, OR 9 , OC(O)R 10 , C(O)R 10 , COOH, CO 2 R 10 , alkyl, haloalkyl, or halo, Z O is hydroxy, R 5 is hydrogen, C(O)R 11 where R 11 is hydrogen or alkyl, or CO 2 R 12 where R 12 is hydrogen or alkyl, R 6 is hydrogen or hydroxy, R 9 is alkyl, arylalkyl or C(O)R 11 where R 11 is as previously defined, and R 10 is hydrogen or alkyl,
and more preferably
R 1 and R 14 are independently hydroxy, methoxy, benzyloxy, acetyloxy or chloro, R 2 , R 15 , and W are independently hydrogen, hydroxy, methoxy, benzyloxy, acetyloxy, methyl, trifluoromethyl or chloro, Z O is hydroxy, R 5 is hydrogen or CO 2 R 12 where R 12 is hydrogen or methyl, and R 6 is hydrogen.
[0110] Particularly preferred compounds of the present invention are selected from:
[0111] The preferred compounds of the present invention also include all derivatives with physiologically cleavable leaving groups that can be cleaved in vivo from the isoflavone or derivative molecule to which it is attached. The leaving groups include acyl, phosphate, sulfate, sulfonate, and preferably are mono-, di- and per-acyl oxy-substituted compounds, where one or more of the pendant hydroxy groups are protected by an acyl group, preferably an acetyl group. Typically acyloxy substituted isoflavones and derivatives thereof are readily cleavable to the corresponding hydroxy substituted compounds. In addition, the protection of functional groups on the isoflavone compounds and derivatives of the present invention can be carried out by well established methods in the art, for example as described in Protective Groups in Organic Syntheses , T. W. Greene, John Wiley & Sons, New York, 1981.
[0112] Chemical and functional equivalents of a particular isoflavone should be understood as molecules exhibiting any one of more of the functional activities of the isoflavone and may be derived from any source such as being chemically synthesised or identified via screening processes such as natural product screening.
[0113] Compounds of the present invention have particular application in the treatment of diseases associated with or resulting from estrogenic effects, androgenic effects, vasodilatory and spasmodic effects, inflammatory effects and oxidative effects.
[0114] The amount of one or more compounds of formula I which is required in a therapeutic treatment according to the invention will depend upon a number of factors, which include the specific application, the nature of the particular compound used, the condition being treated, the mode of administration and the condition of the patient. Compounds of formula I may be administered in a manner and amount as is conventionally practised. See, for example, Goodman and Gilman, The Pharmacological Basis of Therapeutics, 1299 (7th Edition, 1985). The specific dosage utilised will depend upon the condition being treated, the state of the subject, the route of administration and other well known factors as indicated above. In general, a daily dose per patient may be in the range of 0.1 mg to 2 g; typically from 0.5 mg to 1 g; preferably from 50 mg to 200 mg.
[0115] The production of pharmaceutical compositions for the treatment of the therapeutic indications herein described are typically prepared by admixture of the compounds of the invention (for convenience hereafter referred to as the “active compounds”) with one or more pharmaceutically or veterinarially acceptable carriers and/or excipients as are well known in the art.
[0116] The carrier must, of course, be acceptable in the sense of being compatible with any other ingredients in the formulation and must not be deleterious to the subject. The carrier or excipient may be a solid or a liquid, or both, and is preferably formulated with the compound as a unit-dose, for example, a tablet, which may contain from 0.5% to 59% by weight of the active compound, or up to 100% by weight of the active compound. One or more active compounds may be incorporated in the formulations of the invention, which may be prepared by any of the well known techniques of pharmacy consisting essentially of admixing the components, optionally including one or more accessory ingredients.
[0117] The formulations of the invention include those suitable for oral, rectal, optical, buccal (for example, sublingual), parenteral (for example, subcutaneous, intramuscular, intradermal, or intravenous) and transdermal administration, although the most suitable route in any given case will depend on the nature and severity of the condition being treated and on the nature of the particular active compound which is being used.
[0118] Formulation suitable for oral administration may be presented in discrete units, such as capsules, sachets, lozenges, or tablets, each containing a predetermined amount of the active compound; as a powder or granules; as a solution or a suspension in an aqueous or non-aqueous liquid; or as an oil-in-water or water-in-oil emulsion. Such formulations may be prepared by any suitable method of pharmacy which includes the step of bringing into association the active compound and a suitable carrier (which may contain one or more accessory ingredients as noted above). In general, the formulations of the invention are prepared by uniformly and intimately admixing the active compound with a liquid or finely divided solid carrier, or both, and then, if necessary, shaping the resulting mixture such as to form a unit dosage. For example, a tablet may be prepared by compressing or moulding a powder or granules containing the active compound, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing, in a suitable machine, the compound of the free-flowing, such as a powder or granules optionally mixed with a binder, lubricant, inert diluent, and/or surface active/dispersing agent(s). Moulded tablets may be made by moulding, in a suitable machine, the powdered compound moistened with an inert liquid binder.
[0119] Formulations suitable for buccal (sublingual) administration include lozenges comprising the active compound in a flavoured base, usually sucrose and acacia or tragacanth; and pastilles comprising the compound in an inert base such as gelatin and glycerin or sucrose and acacia.
[0120] Compositions of the present invention suitable for parenteral administration conveniently comprise sterile aqueous preparations of the active compounds, which preparations are preferably isotonic with the blood of the intended recipient. These preparations are preferably administered intravenously, although administration may also be effected by means of subcutaneous, intramuscular, or intradermal injection. Such preparations may conveniently be prepared by admixing the compound with water or a glycine buffer and rendering the resulting solution sterile and isotonic with the blood. Injectable formulations according to the invention generally contain from 0.1% to 60% w/v of active compound and are administered at a rate of 0.1 ml/minute/kg.
[0121] Formulations suitable for rectal administration are preferably presented as unit dose suppositories. These may be prepared by admixing the active compound with one or more conventional solid carriers, for example, cocoa butter, and then shaping the resulting mixture.
[0122] Formulations or compositions suitable for topical administration to the skin preferably take the form of an ointment, cream, lotion, paste, gel, spray, aerosol, or oil. Carriers which may be used include Vaseline, lanoline, polyethylene glycols, alcohols, and combination of two or more thereof. The active compound is generally present at a concentration of from 0.1% to 0.5% w/w, for example, from 0.5% to 2% w/w. Examples of such compositions include cosmetic skin creams.
[0123] Formulations suitable for transdermal administration may be presented as discrete patches adapted to remain in intimate contact with the epidermis of the recipient for a prolonged period of time. Such patches suitably contain the active compound as an optionally buffered aqueous solution of, for example, 0.1 M to 0.2 M concentration with respect to the said active compound.
[0124] Formulations suitable for transdermal administration may also be delivered by iontophoresis (see, for example, Pharmaceutical Research 3 (6), 318 (1986)) and typically take the form of an optionally buffered aqueous solution of the active compound. Suitable formulations comprise citrate or bis/tris buffer (pH 6) or ethanol/water and contain from 0.1 M to 0.2 M active ingredient.
[0125] The active compounds may be provided in the form of food stuffs, such as being added to, admixed into, coated, combined or otherwise added to a food stuff. The term food stuff is used in its widest possible sense and includes liquid formulations such as drinks including dairy products and other foods, such as health bars, desserts, etc. Food formulations containing compounds of the invention can be readily prepared according to standard practices.
[0126] Compounds of the present invention have potent antioxidant activity and thus find wide application in pharmaceutical and veterinary uses, in cosmetics such as skin creams to prevent skin ageing, in sun screens, in foods, health drinks, shampoos, and the like.
[0127] It has surprisingly been found that compounds of the formula I interact synergisticly with vitamin E to protect lipids, proteins and other biological molecules from oxidation.
[0128] Accordingly a further aspect of this invention provides a composition comprising one or more compounds of formula I, vitamin E, and optionally a pharmaceutically, veterinarily or cosmetically acceptable carriers and/or excipients.
[0129] Therapeutic methods, uses and compositions may be for administration to humans or animals, such as companion and domestic animals (such as dogs and cats), birds (such as chickens, turkeys, ducks), livestock animals (such as cattle, sheep, pigs and goats) and the like.
[0130] Compounds of formula I may be prepared by standard methods known to those skilled in the art. Suitable methods may be found in, for example, International Patent Applications WO 98/08503 and WO 00/49009 which are incorporated herein in their entirety by reference. Methods which may be employed by those skilled in the art of chemical synthesis for constructing the general ring structures depicted in formulae I and II are depicted in schemes 1-8 below. Chemical functional group protection, deprotection, synthons and other techniques known to those skilled in the art may be used where appropriate in the synthesis of the compounds of the present invention. In the formulae depicted in the schemes below the moities R 1 , R 2 , R 6 , R 8 , R 14 , R 15 , R 16 , W and X are as defined above. The hydroxy moiety Z O may also be protected, deprotected or derived from a synthon as appropriate during the synthesis or administration of the compounds of the present invention. Reduction of the isoflavone derivatives may be effected by procedures well known to those skilled in the art including sodium borohydride reduction, and hydration over metal catalysts such as Pd/C, Pd/CaCO 3 and Platinum(IV)oxide (Adam's catalyst) in protic or aprotic solvents. The end products and isomeric ratios can be varied depending on the catalyst/solvent system chosen. The schemes depicted below are not to be considered limiting on the scope of the invention described herein.
[0131] The invention will now be further described by the following non-limiting examples.
EXAMPLE 1
[heading-0132] General Syntheses of Substituted Isoflavones
[0133] 8-Chloro-4′,6,7-trihydroxyisoflavone (1) was synthesised by the general method of condensing 3-chloro-1,2,4-benzenetriol with 4-hydroxyphenylacetic acid to afford 2-chloro-2,4,5,4′-tetrahydroxydeoxybenzoin according to Scheme 8. Cyclisation of the intermediate deoxybenzoin was achieved by treatment with dimethylformamide and methanesulfonyl chloride in the presence of boron triflouride etherate to afford compound (1).
[0134] In a similar manner numerous other substituted isoflavones and derivatives thereof of general formula (I) and formulae (II)-(VIII) and compounds (2)-(30) can also be synthesised by varying the substitution pattern and/or protecting groups on the phenol derivatives or phenylacetic acid groups. For example starting with 6-methyl-1,2,4-benzenetriol affords 4′,6,7-trihydroxy-5-methylisoflavone (27); whilst use of 3-hydroxy phenyl acetic acid in the general synthetic method affords 3′-hydroxy isoflavone derivatives, such as compound (20).
[0135] It will be appreciated by those skilled in the art that protecting groups may be utilised in the synthetic methods described as appropriate. For example, vicinal hydroxy groups can be protected as cyclic ketals, acetyls, boronates and carbonates according to standard methods known in the art (see for example March, Advanced Organic Chemistry, 3rd Ed., 1985, John Wiley & Sons). Additionally or alternatively well known protection and deprotection methods of functional group chemistry or synthons may be employed (see Green, ibid. or March, ibid., or references cited therein).
[0136] As an example, the starting phenol from Scheme 8 may be first protected as an n-butyl boronate:
and then deprotected as required during the synthesis of the compounds of formula (I).
EXAMPLE 2
[0138] The binding affinity of various compounds of the invention for both subtypes of the estrogen receptor is determined using the “Estrogen Receptor Alpha or Beta Competitor Assay Core HTS Kit” supplied by Panvera Corporation (Product No. P2614/2615). Many of the exemplified and named compounds show good competitive binding to the estrogen receptors ER alpha and ER beta.
[0139] The results show that the compounds of the present invention have particular application in the treatment, prophylaxis or amelioration of diseases associated with or resulting from estrogenic effects, androgenic effects, vasodilatory and spasmodic effects, inflammatory effects and oxidative effects.
[0140] The invention has been described herein, with reference to certain preferred embodiments, in order to enable the reader to practice the invention without undue experimentation. However, a person having ordinary skill in the art will readily recognise that many of the components and parameters may be varied or modified to a certain extent without departing from the scope of the invention. Furthermore, titles, headings, or the like are provided to enhance the reader's comprehension of this document, and should not be read as limiting the scope of the present invention.
[0141] The entire disclosures of all applications, patents and publications, cited herein, if any, are hereby incorporated by reference.
[0142] Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modifications. The invention also includes all of the steps, features, compositions and compounds referred to or indicated in this specification individually or collectively, and any and all combinations of any two or more of said steps or features.
[0143] The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that that prior art forms part of the common general knowledge in the field of endeavour.
|
Isoflavone compounds of the formula (I) or (II) Where R can be R 7? or OR 7? or O and the formula (III) is either a single or double bond extends to Y then Y is an optionally substituted benzyl. W, R 1?, Z o? R 2? and R 7? are as defined in the specification. The compounds are useful for the treatment of certain diseases and disorders, including cancer and inflammation.
| 0 |
FIELD OF THE INVENTION
[0001] The present invention relates to optical implants generally and more particularly to anti-glare solutions for intraocular implants.
BACKGROUND OF THE INVENTION
[0002] The following patent publications are believed to represent the current state of the art:
[0003] U.S. Pat. Nos. 5,628,794; 5,169,597; 6,632,887; 6,613,088 and 6,280,471; and
[0004] U.S. Patent Publication Nos.: 2002/0149741 and 2003/0229303.
SUMMARY OF THE INVENTION
[0005] The present invention seeks to provide an intraocular implant, including an implant body adapted to have mounting haptics attached thereto, the implant body including a generally cylindrical portion and at least one sealing element mounted onto an end of the generally cylindrical portion, the intraocular implant also including at least one lens mounted within the implant body and an anti-glare coating layer covering at least part of an outer area of the generally cylindrical portion, and being operative to prevent glare caused by light rays passing through the implant body from obstructing a user's vision.
[0006] In accordance with a preferred embodiment of the present invention the coating layer includes a metallic layer including a plurality of longitudinal grooves operative to prevent the formation of eddy currents in the coating layer. Preferably, the coating layer is formed of titanium.
[0007] In accordance with another preferred embodiment of the present invention, the anti-glare coating layer is opaque. Preferably, the coating layer is applied onto the generally cylindrical portion by a sputtering process.
[0008] In accordance with yet another preferred embodiment of the present invention the at least one lens has an optical surface having optical power, and an inner boundary of the anti-glare coating layer lies at an edge of the optical surface. Preferably, the anti-glare coating layer covers an outer circumference of the generally cylindrical portion and extends onto the at least one sealing element.
[0009] There is also provided in accordance with another preferred embodiment of the present invention an intraocular implant, including an implant body and at least one lens, the implant body being at least partially coated by a metallic coating having a plurality of grooves formed therein, the grooves being operative to prevent the formation of eddy currents in the coating.
[0010] In accordance with a preferred embodiment of the present invention the coating is an anti-glare coating, operative to prevent glare caused by light rays passing through the implant body from obstructing a user's vision. Preferably, the coating layer is formed of titanium. Additionally or alternatively, the coating layer is opaque.
[0011] In accordance with another preferred embodiment of the present invention the coating layer is applied onto the generally cylindrical portion by a sputtering process. Preferably, the at least one lens has an optical surface having optical power, and an inner boundary of the coating layer lies at an edge of the optical surface. Additionally or alternatively, the implant body includes a generally cylindrical portion and at least one sealing element, and the coating layer covers an outer circumference of the generally cylindrical portion and extends onto the at least one sealing element.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The present invention will be understood and appreciated more fully from the following detailed description, taken in conjunction with the drawings in which:
[0013] FIGS. 1A and 1B are simplified sectional illustration of a field of view widening telescopic implant constructed and operative in accordance with two alternative preferred embodiments of the present invention;
[0014] FIG. 2 is a simplified partially sectional illustration of an implant forming part of an artificial vision system, the implant being constructed and operative in accordance with another preferred embodiment of the present invention;
[0015] FIGS. 3A and 3B are simplified sectional illustrations of an intraocular implant constructed and operative in accordance with two alternative preferred embodiments of the present invention; and
[0016] FIG. 4 is a simplified pictorial illustration of an implant body coated in accordance with yet a further preferred embodiment of the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0017] Reference is now made to FIGS. 1A and 1B , which are simplified sectional illustration of a field of view widening telescopic implant constructed and operative in accordance with two alternative preferred embodiments of the present invention.
[0018] As seen in FIGS. 1A and 1B , the implant preferably comprises an implant body 250 , which is supported by haptics 252 via a haptic mounting structure 254 . The implant body 250 typically comprises mutually sealed forward and rearward cylindrical housing portions 256 and 258 respectively and a transparent forward window 260 sealing the forward cylindrical portion 256 . Typically, the implant body 250 is formed of glass housing portions, which are sealed by glass laser welding.
[0019] Disposed rearwardly of the forward window 260 in forward cylindrical portion 256 is a negative lens 262 . Fixed to negative lens 262 as a doublet is a magnification lens 264 , which resides partially in the forward cylindrical housing portion 256 and partially in the rearward cylindrical housing portion 258 . Disposed rearwardly of the magnification lens 264 is a positive lens 266 , which is mounted in sealing engagement with the rearward cylindrical housing portion 258 of implant body 250 and defines a rearward facing window.
[0020] Preferably, the negative lens 262 and the positive lens 266 include refractive and diffractive optical elements. Typically, the negative lens 262 and the positive lens 266 are coated with optical coatings.
[0021] It is an important feature of the present invention that the interior of the implant body 250 is sealed from the exterior thereof, so as to prevent liquids or vapors from entering the implant. It is also an important feature of the present invention that three air gaps, designated by reference numerals 270 , 272 and 274 , are provided to enhance refraction. The precision of the location of a contact point 276 between lenses 264 and 266 and of a peripheral contact area 278 between lenses 262 and 264 relative to an axis 280 is also of importance to maintain desired focus.
[0022] In accordance with a preferred embodiment of the present invention, a resilient O-ring 282 or other element having a similar function is provided to urge and retain lenses 264 and 266 in touching engagement at contact point 276 .
[0023] Alternatively, the implant body may be formed of a single cylinder or of any suitable number of cylindrical portions. Furthermore, any suitable combination of any suitable number of lenses may be employed. Preferably, the haptics 252 are formed of a suitable polymer, the implant body 250 is formed of biocompatible glass and the forward window 260 and the lens 266 are formed of glass and are laser welded in sealing engagement with body 250 .
[0024] Turning to FIG. 1A , it is seen that a metallic anti-glare coating layer 292 covers the outer circumference of forward window 260 of the implant body 250 . The coating layer 292 is opaque, and therefore prevents light rays which pass through the transparent implant body 250 creating a glare which obstructs a user's vision.
[0025] As seen in the enlarged portion of FIG. 1A , the coating layer 292 includes a plurality of longitudinal grooves 294 which are operative to prevent the formation of eddy currents in the coating layer 292 . The coating layer 292 is preferably formed of Titanium and is preferably applied to the implant body by a sputtering process.
[0026] It is appreciated that the intraocular implant 250 includes an optical surface having optical power, and that an inner boundary 296 of the coating layer 292 lies at an edge of the optical surface.
[0027] Turning now to FIG. 1B , it is seen that a metallic anti-glare coating layer 302 covers the outer circumference of the implant body 250 and extends onto forward window 260 , as indicated by reference numeral 303 . The coating layer 302 is opaque, and therefore prevents light rays which pass through the transparent implant body 250 creating a glare which obstructs a user's vision.
[0028] As seen in the enlarged portion of FIG. 1B , the coating layer 302 includes a plurality of longitudinal grooves 304 which are operative to prevent the formation of eddy currents in the coating layer 302 . The coating layer 302 is preferably formed of Titanium and is preferably applied to the implant body by a sputtering process.
[0029] It is appreciated that the intraocular implant 250 includes an optical surface having optical power, and that an inner boundary 306 of portion 303 of the coating layer 302 lies at an edge of the optical surface.
[0030] Reference is now made to FIG. 2 , which is a simplified partially sectional illustration of an implant forming part of an artificial vision system, the implant being constructed and operative in accordance with another preferred embodiment of the present invention.
[0031] FIG. 2 illustrates an intraocular implant 400 which preferably forms part of an artificial vision system, such as that described in Applicants' U.S. patent application Ser. No. 10/489,388, the disclosure of which is hereby incorporated by reference. The intraocular implant 400 includes an intraocular implant body 402 having mounting haptics 404 . Hermetically sealed to implant body 402 are a front sealing plate 406 and a back sealing plate 408 . Back sealing plate 408 is transparent. An internal imaging device (not shown) is preferably mounted on an outside surface of front sealing plate 406 . Capsules of this type are described in applicants' U.S. patent application Ser. No. 09/678,559, filed Oct. 3, 2000 and entitled “TELESCOPIC INTRAOCULAR LENS”, which is a divisional application of U.S. patent application Ser. No. 09/222,330, filed Dec. 29, 1998 and entitled “TELESCOPIC INTRAOCULAR LENS”, subsequently abandoned, and U.S. patent application Ser. No. 09/721,916, filed Nov. 27, 2000 and entitled “TELESCOPIC INTRAOCULAR LENS”, the disclosures of which are hereby incorporated by reference.
[0032] Preferably disposed within implant 400 is an electronic circuit and display assembly, which preferably includes electronic display 410 which is coupled to electronic circuitry 412 , preferably including a wireless receiver for image data. Display 410 is arranged to lie generally parallel to front sealing plate 406 , while electronic circuitry 412 is preferably embodied on a flexible circuit board 414 which is arranged to lie in a cylindrical configuration, peripherally of the optical path between display 410 and back sealing plate 408 , so as not to interfere with the optical pathway between the display 410 , focusing optics here shown as a lens 416 , and the user's retina. It is appreciated that the focusing optics may also comprise multiple lenses.
[0033] As seen in FIG. 2 , a metallic anti-glare coating layer 422 covers the outer circumference of the implant body 402 , and extends onto front sealing plate 406 as indicated by reference numeral 423 . The coating layer 422 is opaque, and therefore prevents light rays which pass through the transparent implant body 402 creating a glare which obstructs a user's vision.
[0034] As seen in the enlarged portion of FIG. 2 , the coating layer 422 includes a plurality of longitudinal grooves 424 which are operative to prevent the formation of eddy currents in the coating layer 422 . The coating layer 422 is preferably formed of Titanium and is preferably applied to the implant body by a sputtering process.
[0035] It is appreciated that the intraocular implant 400 includes an optical surface having optical power, and that an inner boundary 426 of portion 423 of the coating layer 422 lies at an edge of the optical surface.
[0036] Reference is now made to FIGS. 3A and 3B , which are simplified sectional illustrations of an intraocular implant constructed and operative in accordance with two alternative preferred embodiments of the present invention.
[0037] FIGS. 3A and 3B illustrate a telescope 500 , suitable for connection to haptics (not shown) for implantation in a human eye. The telescope 500 comprises a telescope body 512 , typically of circular cylindrical configuration and formed of glass. Alternatively, the telescope body may be formed of other non-porous bio-compatible materials or may be formed of other materials and be coated with a suitable non-porous bio-compatible material.
[0038] Sealed to anterior and posterior ends 514 and 516 of the telescope body 512 are respective windows 518 and 520 which preferably do not have optical power. Mounted within telescope body 512 intermediate windows 518 and 520 are forward and rearward lenses, 522 and 524 . Preferably air gaps 526 and 528 are defined between lenses 522 and 524 and respective windows 518 and 520 and an air gap 530 is defined between lenses 522 and 524 .
[0039] Turning to FIG. 3A , it is seen that a metallic anti-glare coating layer 532 covers the outer circumference of forward window 518 of the implant body 512 . The coating layer 532 is opaque, and therefore prevents light rays which pass through the transparent implant body 512 creating a glare which obstructs a user's vision.
[0040] As seen in the enlarged portion of FIG. 3A , the coating layer 532 includes a plurality of longitudinal grooves 534 which are operative to prevent the formation of eddy currents in the coating layer 532 . The coating layer 532 is preferably formed of Titanium and is preferably applied to the implant body by a sputtering process.
[0041] It is appreciated that the intraocular implant 500 includes an optical surface having optical power, and that an inner boundary 536 of the coating layer 532 lies at an edge of the optical surface.
[0042] Turning now to FIG. 3B , it is seen that a metallic anti-glare coating layer 542 covers the outer circumference of the implant body 512 and extends onto forward window 518 and onto rearward window 520 , as indicated by respective reference numerals 543 and 544 . The coating layer 542 is opaque, and therefore prevents light rays which pass through the transparent implant body 512 creating a glare which obstructs a user's vision.
[0043] As seen in the enlarged portion of FIG. 3B , the coating layer 542 includes a plurality of longitudinal grooves 545 which are operative to prevent the formation of eddy currents in the coating layer 542 . The coating layer 542 is preferably formed of Titanium and is preferably applied to the implant body by a sputtering process.
[0044] It is appreciated that the intraocular implant 500 includes an optical surface having optical power, and that an inner boundary 546 of portion 543 of the coating layer 542 lies at an edge of the optical surface.
[0045] Reference is now made to FIG. 4 , which is a simplified pictorial illustration of an implant body coated in accordance with yet a further preferred embodiment of the present invention, the implant body being of the type described hereinabove with reference to any of FIGS. 1A-3B .
[0046] As seen in FIG. 4 , an implant body 700 has a generally circular cylindrical configuration, and typically has one or more lenses (not shown) disposed therein. The implant body 700 is typically sealed in the front and back by lenses and/or windows 702 .
[0047] A metallic anti-glare coating layer 712 covers the outer circumference of the implant body 700 as indicated by reference numeral 714 , and extends onto the front and rear sealing elements of the implant body 700 , which may be windows or lenses, as indicated by reference numeral 716 . The coating layer 712 is opaque, and therefore prevents light rays which pass through the transparent implant body 700 creating a glare which obstructs a user's vision. The coating layer 712 includes a plurality of longitudinal grooves 718 , which extend along portions 714 and 716 thereof, and which are operative to prevent the formation of eddy currents in the coating layer 712 . The coating layer 712 is preferably formed of Titanium and is preferably applied to the implant body by a sputtering process.
[0048] It will be appreciated by persons skilled in the art that the present invention is not limited by what has been particularly shown and described hereinabove. Rather the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove as well as variations and modifications which would occur to persons skilled in the art upon reading the specification and which are not in the prior art.
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An intraocular implant, including an implant body adapted to have mounting haptics attached thereto, the implant body including a generally cylindrical portion and at least one sealing element mounted onto an end of the generally cylindrical portion, the intraocular implant also including at least one lens mounted within the implant body and an anti-glare coating layer covering at least part of an outer area of the generally cylindrical portion, and being operative to prevent glare caused by light rays passing through the implant body from obstructing a user's vision.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a telescopic cover for use in a machine tool or other industrial machinery.
2. Description of Related Art
A telescopic cover that covers a feed mechanism, such as a feed shaft and a guide face of a machine tool table, to protect it from cutting fluid, chips, etc. is provided with telescopic cover members adapted to expand and contract for protection of the feed mechanism. The cover member however sometimes meanders when it is in motion, and a large impact is caused for example when it stops after a sudden motion.
In a known method to relieve such impact, there are provided telescopic cover members each formed at its distal end with a bellow seal in the form of a wiper. When one of the cover members projects at the maximum from an adjacent cover member, a stopper plate for preventing detachment formed in a rear end of the cover member is in contact with the bellow seal. An impact produced when the cover member projects is thereby relieved (refer to JP 6-11946U).
Also known is a telescopic cover having cover members each provided at a distal end thereof with a wiper clip or the like for removing chips adhered to the telescopic cover (refer to JP2000-308944A and JP2000-308945A).
Further known is a telescopic cover having cover members whose distal ends are each provided with a wiper of a rubber elastic material for preventing intrusion of chips, dusts, oils, or the like for protection of a sliding portion of a machine tool. In order to prevent the increase in friction resistance to the wipers, each wiper is fixed with a hard resin adapted for contact with a sliding face of an adjacent cover member, thus decreasing the friction resistance (refer to JP 3050875Y).
Another cover assembly is known, which includes a stationary cover, a movable cover, and a thin metallic elastic member extending from one cover face for contact with another cover face to seal a gap therebetween, whereby foreign matter adhered to the cover is removed (refer to JP 2-48207Y).
As mentioned above, the telescopic cover is generally so designed that, with a movement of a movable section, a corresponding one or more cover members are moved so that a cover region of the telescopic cover is expanded or contracted as a whole. However, there is a limit in an amount of motion of each cover member, and thus when one of the cover members reaches the stroke limit, it collides with the adjacent cover member to produce an impact. To obviate this, the first-mentioned JP 6-11946U has telescopic cover members each adapted, when projecting, to collide at its rear end with a bellow seal, whereby an impact is relieved. However, when the telescopic cover member retracts into the adjacent one to thereby contract the telescopic cover, these cover members collide with each other. Furthermore, if a gap between adjacent cover members increases due to the wearing away of their sliding parts or the like, the meander of the telescopic cover becomes large. As a result, large noise is produced, and the cover members are liable to be damaged. Although the problem of meandering is lessened in a fixed-end type telescopic cover having both ends respectively fixed to stationary and movable parts, a telescopic cover fixed only at one end is liable to meander, causing a problem.
Technical arts disclosed in the secondly and subsequently mentioned publications are devoted to remove foreign matter adhered to a surface of the telescopic cover or the like, and never contemplate to relieve collision between cover members or prevent the meandering of the telescopic cover.
SUMMARY OF THE INVENTION
The present invention provides a telescopic cover capable of reducing impact of cover members in stopping their motions and also meandering.
The telescopic cover of the present invention comprises: a plurality of cover members having different sizes and successively stacked in a telescopic manner for making relative motion respectively so as to be expandable and contractible as a whole; and braking means provided between at least two adjacent cover members in said plurality of cover members to apply pressing force to the relative motion of the adjacent cover members in a direction substantially perpendicular to the relative motion, to thereby brake the relative motion.
The braking means may be mounted on one of the two adjacent cover members to apply the pressing force to the other adjacent cover member.
The telescopic cover may further comprise a pressing-force adjusting mechanism for adjusting the pressing force applied by the braking means.
The braking means may comprise an elastic member mounted on one of the two adjacent cover members and a pressing member urged by the elastic member to press against the other of the two adjacent cover members.
Alternatively, the braking means may comprise an elastic member having one end mounted on one of the two adjacent cover members and the other end to press against the other of the two adjacent cover members.
The pressing-force adjusting mechanism may be mounted on the one of the two adjacent cover members to be in contact with the elastic member.
With the above arrangements, the cover member in motion is pressed by the braking means so that the pressing force generates a friction force serving as a braking force. Thus, the impact of cover members in stopping their motions is reduced. Further, since the cover member is always pressed by the braking means, the orientation of the cover member is retained constant, and the meandering of the telescopic cover is suppressed when it expands or contracts.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic view of one embodiment of this invention;
FIG. 2 is a sectional view of a braking mechanism according to the one embodiment;
FIG. 3 is a view for explaining a gap between cover members;
FIG. 4 is a view for explaining how to suppress a change in orientation of cover members;
FIG. 5 is a view for explaining a braking mechanism according to a second embodiment;
FIG. 6 is a view for explaining a braking mechanism according to a third embodiment; and
FIG. 7 is a view for explaining a braking mechanism according to a fourth embodiment.
DETAILED DESCRIPTION
FIG. 1 is a schematic view of a telescopic cover according to one embodiment of this invention. In this embodiment, the telescopic cover is constituted by n cover members including first to n'th cover members C 1 , . . . , C n . The first cover member C 1 is provided with a mounting portion 1 through which the telescopic cover is mounted to a stationary section or the like. The second cover member C 2 is slidably fitted into the first cover member C 1 in a telescopic fashion. Similarly, the third cover member C 3 (not shown) is slidably fitted into the second cover member C 2 . In the same way, the (i+1)'th cover member C i+1 is slidably fitted into the i'th cover member C i in a telescopic fashion.
Braking mechanisms 2 are respectively provided at distal end portions of the i'th cover members C i (into and out of which are the (i+1)'th cover members C i+1 , where i varies from 1 to n−1). In this embodiment, the cover member is provided at an upper face and one side face thereof with the braking mechanisms 2 .
FIG. 2 is a sectional view for explaining the braking mechanism 2 . The braking mechanism 2 is constituted by an orientation maintaining device 22 having a central blind hole in which is received an elastic member 21 (constituted by a spring, rubber, resin, or the like, and the one constituted by a spring is shown by way of example in FIG. 2 ), a slide member 23 adapted to project by being urged by the elastic member 21 , and fasting members 24 such as bolts by which the braking mechanism 2 is fixed to the cover member.
By fixing the orientation maintaining device 22 to the cover member C i (first cover member C 1 in the example shown in FIG. 2 ) using the fastening members 24 , the braking mechanism 2 is mounted to the cover member C i in such a manner that the slide member 23 adapted to project by being urged by the elastic member 21 presses the (i+1)'th cover member C i+1 that is slidably received in the cover member C i (first cover member C 1 ). In the example shown in FIG. 2 , the braking mechanisms 2 are mounted to the cover member C 1 so that slide members 23 press the cover member C 2 . The cover member C 2 (C i+1 ) is adapted to move relative to the cover member C 1 (C i ). When the cover member C 2 (C i+1 ) moves, it slides while being pressed by the slide members 23 . Therefore, as shown in FIG. 2 , a friction force F is generated that is in proportion to a pressing force B applied from the elastic member 21 to the slide member 23 , whereby the cover member C 2 (C i+1 ) is braked.
As a result, when one of the cover members of the telescopic cover moves even at a high speed, friction forces produced by pressing forces applied from the slide members 23 of the braking mechanisms 2 and serving as braking forces are applied to the moving cover member, thus preventing occurrence of a large impact when the cover member stops moving. Since the moving cover member slides on the slide members 23 , it is preferable that the slide members 23 be made of brass, resin, or the like to prevent them from being worn.
In the meantime, the braking mechanism 2 may be provided on the upper face and one side face of the distal end of each cover member, as shown in FIG. 1 . Alternatively, the braking mechanism 2 may be provided on only the upper face, both or only one of the side faces, or the upper and both side faces. As shown in FIG. 1 , the braking mechanism 2 provided on the side face applies a pressing force B 1 that exerts in a direction perpendicular to the moving direction A of the cover member, whereas the braking mechanism 2 provided on the upper face applies a pressing force B 2 exerting in a direction perpendicular to the moving direction A of the cover member, generating a friction force.
As explained above, the cover member C i+1 that moves relative to the cover member C i in a telescopic fashion is pressed by the braking mechanisms 2 provided on the upper and side faces of the cover member C i . Thus, a gap between the cover members C i and C i+1 is maintained constant, thereby suppressing a change in the orientation of the cover member C i+1 which is moving.
FIG. 3 is a view in which a gap between the cover members C 1 and C 2 is seen from front. More specifically, FIG. 3 is a view showing the gap 3 between the cover members C 1 and C 2 in a case where the braking mechanism 2 is provided on the upper face and both the side faces of the cover member C 1 . Gaps between the cover members C 1 and C 2 on both sides are maintained constant by means of the slide members 23 that project by being urged by the elastic members 21 of the braking mechanisms 2 . In addition, a gap between the upper faces of the cover members C 1 and C 2 is also maintained constant by means of the slide member 23 provided on the upper face. As a result, the orientation of the moving cover member C 2 is kept unchanged.
FIG. 4 is a view for explaining a change in the orientation of the cover member. As in the case of FIG. 3 , an explanation will be given by taking the cover members C 1 and C 2 as example. When no braking mechanism 2 is provided on the cover member C 1 , there occurs a parallel displacement of the cover member C 2 in the left and right direction, as shown by an arrow α in FIG. 4 . Also, the cover member C 2 rotates as shown by an arrow β, causing a change in the orientation of the cover member C 2 . On the contrary, when the braking mechanism 2 is provided on both sides of the cover member C 1 (or provided on either one of the sides), the cover member C 2 is in contact with the slide members 23 , whereby the gaps 3 on the both sides are maintained constant, without causing a parallel displacement in the left and right direction in FIG. 4 . Also in the vertical direction, the cover member C 2 is always pressed by the slide member 23 of the braking mechanism 2 that is provided on the upper face of the cover member C 1 , and no parallel displacement is caused in the vertical direction. Since the cover member C 2 is pressed by the slide members 23 of the braking mechanisms 2 in such a manner that the gaps between the cover members in the vertical and width wise directions are maintained constant, the cover member C 2 is prevented from being rotated around the moving direction and a direction perpendicular thereto, thus suppressing a change in the orientation of the moving cover member C 2 .
FIG. 5 shows a second embodiment of the braking mechanism. This braking mechanism 4 is constituted by an elastic member 41 (the one shown by way of example in FIG. 5 is formed by a plate spring, but other elastic member made of rubber or resin may be used), and a fastening member 42 such as a screw for fixing the elastic member 41 to the cover member. As in the first embodiment, the braking mechanism 4 is fixed to a distal end of the cover member ci of the telescopic cover (instead of the braking mechanism 2 of FIG. 1 , the braking mechanism 4 is mounted). Specifically, the elastic member 41 is fixed at its one end portion to a distal end of the cover member ci by means of the fastening member 42 . The elastic member 41 has another end portion that is flat and adapted to press a surface of the cover member Ci+1, which is movable relative to the cover member Ci in a telescopic fashion. In this embodiment, the flat distal end of the elastic member 41 serves as the slide member 43 .
When the cover member C i+1 moves relative to the cover member C i , therefore, it is always pressed by the elastic member 41 . Thus, the cover member C i+1 is braked by a friction force due to the pressing force of the elastic member 41 . Moreover, the cover member C i+1 is maintained in position by means of the elastic member 41 as viewed in the pressing direction of the elastic member 41 , so that a change in the orientation of the cover member C i+1 is suppressed. That is, the braking mechanism 4 of the second embodiment achieves the functions similar to those of the braking mechanism 2 of the first embodiment.
FIG. 6 is a view for explaining a third embodiment of this invention. The braking mechanisms 2 , 4 of the first and second embodiments produce a constant pressing force for pressing the cover member, which is determined at the time of design. Therefore, even if an excess or deficiency is caused in an actual braking force, it is difficult to make an adjustment. In this regard, it is the third embodiment shown in FIG. 6 that makes it easy to adjust the pressing force.
The braking mechanism 5 of the third embodiment is the one in which a pressing-force adjustment mechanism is added to the first embodiment. The braking mechanism 5 is comprised of an elastic member 51 such as a spring, an orientation maintaining device 52 , a slide member 53 , fastening members 54 such as bolts, a bolt 55 , and a nut 56 .
The orientation maintaining device 52 is formed at its central part with a hole 57 in which the elastic member 51 and the slide member 53 are received. The hole 57 has an upper end portion thereof formed with threads with which the bolt 55 is threadedly engaged. By means of the fastening members 54 , the braking mechanism 5 is fastened to a distal end of each cover member C i (cover member C 1 in FIG. 6 ) of the telescopic cover. Used as the fastening member 54 in this embodiment is a fastening screw such as a bolt. If the cover member C i is thin in thickness, it is impossible to appropriately form a threaded portion in the cover member C i for threaded engagement with the fastening screw. For this reason, a reinforcing member 58 is fixed beforehand to the cover member C i using bolts, welding or the like, and the cover member C i and the reinforcing member 58 are tapped for threaded engagement with the threads of the fastening member 54 , whereby the braking mechanism 5 is reliably mounted.
Then, the bolt 55 is threadedly engaged with the threads of the upper end portion of the hole 57 , thereby pressing the slide member 53 through the medium of the elastic member (spring) 51 . The slide member 53 presses a surface of the cover member C i+1 (cover member C 2 in FIG. 6 ) that moves relative to the cover member C i in a telescopic fashion. The pressing force F for pressing the cover member C i+1 can be increased or decreased for adjustment by increasing or decreasing an amount of screwing the bolt 55 . The bolt 55 and the elastic member 51 constitute the pressing-force adjusting mechanism. In the meantime, the nut 56 threadedly engaged with the bolt 55 serves to fix the bolt 55 , thereby keeping the amount of screwing the bolt 55 unchanged, even if vibration or the like is applied after completion of the pressing force adjustment.
FIG. 7 is a view for explaining a forth embodiment of this invention. This embodiment is the one in which a pressing-force adjusting mechanism is added to the second embodiment.
A braking mechanism 6 of the fourth embodiment is substantially the same in constriction as the second embodiment, but differs in that a bolt 61 and a nut 62 are added as the pressing-force adjusting mechanism. In other respect, it is the same as that of the second embodiment. The same elements as those of the second embodiment shown in FIG. 5 are denoted by the same numerals.
As with the second embodiment, the elastic member 41 is fixed at its one end to the cover member C i of the telescopic cover by means of the fastening member 42 . In the vicinity of the location where the elastic member 41 is fixed, a tap hole 63 is formed in that position of the cover member C i which corresponds to a position which the elastic member 41 passes through. The bolt 61 threadedly engaged with the tap hole 63 has its distal end that is adapted for contact with the elastic member 41 , and the nut 62 is threadedly engaged with the bolt 61 . The pressing force of the elastic member 41 for pressing the cover member C i+1 is determined by adjusting an amount of screwing the bolt 61 into the tap hole 63 . Specifically, by adjusting the amount of screwing the bolt 61 , the position of the distal end of the bolt 61 is adjusted, thereby adjusting an amount of deviation of the elastic member 41 toward the cover member C i+1 with the distal end of the bolt 61 .
After completion of the pressing force adjustment, the bolt 61 is fixed by the nut 62 to avoid a change in the amount of screwing the bolt 61 due to vibration or the like. Since the other configuration is the same as the second embodiment, a further explanation will be omitted.
In each of the foregoing embodiments, the braking mechanism 2 or 4 is fixed to the outer cover member C i , and the slide member is pressed by an elastic force of the elastic member against the inner cover member C i+1 disposed telescopically in the outer cover member C i , thereby braking the movement of the cover member C i+1 and maintaining the orientation thereof. Alternatively, the braking mechanism 2 or 4 may be fixed to the inner telescopic cover member C i+1 and the outer cover member C i may be pressed by the slide member, thereby braking the relative movement between the cover members C i and C i+1 and maintaining the orientation thereof.
The present invention is also applicable to an angle telescopic cover whose central part (center line of the cover member that is in parallel to the line extending in the moving direction) is raised, a telescopic cover whose opposite ends are connected to other members, or a telescopic cover having a pantograph mechanism.
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A telescopic cover which relieves impact caused when a cover member is stopped moving and which is less meandering. A braking mechanism is provided between one of two adjacent cover members of the telescopic cover and the other of the two adjacent cover members which telescopically moves into and out of the one cover member. The braking mechanism is provided at a distal end portion of the one cover member, and has an elastic member that presses a slide member against the other cover member. When the other cover member moves relatively to the one cover member, a friction force generated by a pressing force of the slide member serves to brake the movement of the other cover member, whereby impact caused when the other cover member stops moving is relieved. The cover member in motion is always pressed by the slide member with an orientation thereof maintained.
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BACKGROUND OF THE INVENTION
The present invention concerns an automatic control of a clutch in the drive train of a motor vehicle, having a transmission shifted by the driver between different transmission stages or gears and an engine controlled by the driver by means of a control element, for example a gas pedal. The clutch is automatically set by a motorized adjusting unit, actuated by the control, to a creeping torque at low travelling speed or when the vehicle is stationary and the transmission stage has been selected, the brake is unactuated and the control element is not actuated.
In motor vehicles with customary internal combustion engines, a transmission must be arranged in the drive train to allow the transmission ratio between the speed of the vehicle engine and the speed of the drive wheels to be changed according to the respective travelling speed and loading of the vehicle. In customary manually shifted transmissions, during the change of a transmission stage the power flow between engine and drive wheels has to be interrupted by releasing the clutch.
When starting the vehicle, the clutch must operate with slip, since the aforementioned transmission is not able to operate steplessly and conventional vehicle engines, in particular internal combustion engines, can only operate and deliver adequate power above a minimum speed.
It is known in principle to use automatic clutches for this purpose so that a clutch is automatically released when changing a transmission stage and is subsequently re-engaged. In starting situations, the clutch initially transmits only a limited torque, i.e. the creeping torque, which is adequate for making the vehicle start to slowly creep forward under normal driving conditions. If the vehicle is then accelerated by corresponding actuation of the gas pedal, the torque which can be transmitted by the clutch increases, so that, depending on the respective operating parameters, at a varying level of engine speed the clutch can transmit a torque which is above the engine torque.
It is known from EP 03 75 162 B1 to allow the automatic control of the clutch also to operate in dependence on the brake actuation in a creeping phase of the vehicle.
SUMMARY OF THE INVENTION
The object of the invention is thus to optimize the control of the clutch in the creeping phase.
This object is achieved according to the invention by initially setting a high creeping torque, at low travelling speed or when the vehicle is stationary, the transmission stage has been selected, the brake is unactuated and the control element is not actuated. The high creeping torque is automatically reduced after a predetermined time period if the brake continues to be unactuated and the gas pedal is not actuated.
In particular, the relatively high creeping torque can be initially set during starting, even after ending a brake actuation.
The invention is based on the general idea of controlling the clutch at the beginning of a starting situation, i.e. after selecting a transmission stage and ending a brake actuation and with the gas pedal not actuated, initially to deliver a relatively high creeping torque, in order to ensure that the vehicle can start reliably and comparatively rapidly. Should the gas pedal continue to remain unactuated within the predetermined time period, this is an indication that this is not a "normal" starting situation and the torque effective for driving the vehicle should be reduced. This at the same time protects the clutch against excessive wear. This applies in particular if the driver should hold a stationary or virtually stationary vehicle on an incline just by using the creeping torque of the clutch.
According to a preferred embodiment of the invention, the reduction in the creeping torque may be relinquished if a threshhold value for the travelling speed has been exceeded. This is because a higher travelling speed often indicates that a starting phase is unlikely to be terminated by the driver. Furthermore, it is ensured on inclines that the engine can, if required, have a braking effect even at relatively low travelling speed.
In addition or alternatively, it may be envisaged to monitor the difference in speed between the input and output of the clutch and not to reduce the creeping torque if the input and output of the clutch have reached speeds which are approaching one another or the same as one another. It is virtually inevitable that such rotational speed conditions have the consequence that the vehicle is running at a higher travelling speed, since an automatic electronic engine control customary in modern engines ensures virtually always that the engine, and consequently the clutch input, rotate at a minimum speed.
Otherwise, with regard to preferred features of the invention, reference is made to the claims and the following explanation of the drawing, on the basis of which a particularly preferred embodiment of the invention is described.
BRIEF DESCRIPTION OF THE DRAWING
In the drawing, the single Figure shows a schematized representation of a drive train of a motor vehicle as well as the components essential for the clutch control.
DESCRIPTION OF THE PREFERRED EMBODIMENT
An internal combustion engine 1 is connected in drive terms via an automatically actuated clutch 2 with a transmission 3, the transmission stages or gears of which are changed by manual actuation of a shift lever 4, and a drive shaft 5, for example a cardan shaft, to drive wheels 6 of a motor vehicle, otherwise not represented in any more detail.
The actuation of the clutch 2 takes place automatically by means of a motorized adjusting unit 7, which is actuated by a control circuit 8. The control circuit 8 takes into account a variety of parameters and is connected for this purpose to an extensive system of sensors.
The system of sensors comprises a sensor arrangement 9, which is assigned to the transmission 3 or the shift lever 4 and senses the positions and/or movements of the latter and consequently registers the respectively selected transmission stage or the respectively selected gear. The position of an element serving for controlling the power of the engine 1, for example a gas pedal actuated by the driver, is registered by a sensor 10. A displacement pickup 11 senses the travel of the adjusting unit 7 and consequently a parameter which is analogous to the value of the torque which can be transmitted by the automatic clutch 2. Furthermore, the control circuit 8 is connected to an engine control 12, the signals of which reproduce, inter alia, the speed of the engine, the torque of the engine 1 and an actuation of a control element for the power of the engine 1, for example the actuation of a gas pedal by the driver. A signalling device 13 registers whether a service brake of the vehicle is actuated. This signalling device 13 may be, for example, a brake light switch, by means of which the brake lights are controlled when the service brake is actuated. The wheel speeds, and consequently the travelling speed of the vehicle, are sensed by means of speed pickups 14, which are assigned to the vehicle wheels. These speed pickups 14 often also have the function of providing the necessary information on the turning of the wheels for an anti-lock braking system.
On the basis of the exchange of information with the engine control 12, the control circuit 8 can determine the torque transmitted in each case by the clutch 2 in dependence on the position of the adjusting unit 7. At constant travelling speed, the following applies for the torque M K transmitted by the clutch 2:
M.sub.K =M.sub.mot -J.sub.mot dw.sub.Mot /dt.
where M mot is the torque generated by the engine 1, which is detected by the engine control 12, J mot is the moment of inertia of the engine 1, which is predetermined by the design of the engine 1, and w Mot is the speed of the engine 1. t denotes time.
Since all engine-related variables can be sensed by the engine control 12 and it can be detected from the signals of the speed pickups 14 whether the vehicle is travelling at approximately constant speed, the control circuit 8 can often "detect" on the basis of its interaction with the engine control 12 and the speed pickups 14 the respective clutch torque M K . In addition, the control circuit 8 knows from the signals of the displacement pickup 11 the position of the adjusting unit 7, so that the control circuit 8 can also often determine or update the proportionality between the clutch torque M K and the travel of the adjusting unit 7. As a result, the control circuit 8 thus "knows" the transmissible torque respectively set at the clutch 2.
In a starting situation, i.e. when the vehicle is stationary or at very low travelling speed, with an unactuated vehicle brake and the gas pedal or the like not actuated, the control circuit 8 initially sets the adjusting unit 7 such that the clutch 2 transmits a comparatively high creeping torque and the vehicle has a pronounced creeping tendency. If the gas pedal continues not to be actuated and the vehicle brake is unactuated, this state is maintained only for a predetermined limited time period, for example a few seconds. Thereafter, the torque which can be transmitted by the clutch 2 is reduced, thereby also reducing the tendency of the vehicle to creep.
Should the vehicle brake then be actuated, on ending of the brake actuation and with an unactuated gas pedal and the transmission stage selected, initially the high creeping torque can in turn be set and then reduced again, if appropriate, after the aforementioned time period.
Should the vehicle exceed a threshold value for the travelling speed during the time period with the high creeping torque, a reduction in the creeping torque may be relinquished.
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Disclosed is an automatic clutch intended for use in an engine-transmission unit of a vehicle. When starting up, the clutch transmits first a high torque for a very slow speed, which is then reduced after a set lapse of time if a threshold value is exceeded.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to apparatus for eliminating slack in driven cables and, in particular, to apparatus for eliminating slack in motorized cables for raising and lowering autoclave and sterilizer doors.
2. Description of the Invention Background
There exists a wide variety of cable assisted devices adapted to open and close doors. In particular, devices such as the one described in U.S. Pat. No. 1,358,859 employ cables and pulleys to assist in the opening and closing of doors that are heavy and cumbersome to operate. In that device, a counterweight is attached to the free end of the cable in an effort to counteract the weight of the door so that it can be lifted more easily. The counterweight also serves to remove the slack from the cable to thereby prevent the cable from tracking off the attending pulleys.
Cable assisted devices are also used to effect the opening and closing of chamber doors on autoclaves and sterilizers used in the medical industry. In those types of applications, the chamber door is usually arranged to slide vertically within corresponding guide tracks that are mounted to the open end of the chamber. The door is suspended by a cable and pulley system that controls the movement of the door relative to the end of the chamber. Typically, one end of the cable is attached to a take-up drum that is rotatably driven by a reversible gear motor; the other end of the cable is connected to a counter weight that assists the door opening process. To close the door, the motorized take-up drum is rotated to accumulate the cable thereon. This action causes the door to slide vertically upward to a closed position. The door is opened by simply reversing the rotation of the take-up drum which permits the cable to slowly unwind therefrom. The weight of the door along with the counterweight that is attached to the free end of the cable keep the cable taut as it unwinds from the drum.
The door is lowered in this manner until it reaches a fully opened position. A stop switch arranged to detect when the door has reached the open position causes the gear motor to be de-energized. However, due to the inertia of the gear motor arrangement, the take-up drum typically continues to rotate for a short time after the gear motor has been de-energized. That additional rotation permits an additional length of cable to unwind from the take-up drum causing the cable to become slackened on the attending pulleys. Often, depending upon the amount of cable slack introduced, the cable is permitted to track off the attending pulleys causing malfunction of the door drive system. This problem has heretofore been typically alleviated by employing an expensive electro-mechanical brake system to stop the rotation of the take-up drum as soon as the gear motor is de-energized by the stop switch. Thus, the need exists for a method of eliminating the cable slack without the use of expensive electrically controlled components such as electro-mechanical brakes.
Another problem typically encountered with prior cable systems is that a gear motor having high starting torque capabilities must be used. More specifically, the prior cable and gear motor arrangements cause the gear motor to encounter a load corresponding to the weight of the door and the inertia of the system immediately upon being activated. As such, a gear motor that is capable of developing the starting torque necessary to immediately overcome the weight of the door and the inertia associated with the cable controlled system must be used. It will be appreciated that gear motors having that kind of starting torque capabilities are larger and more expensive than similar gear motors having smaller starting torque capabilities. Thus, the need exists for a simple cable operated door system wherein a smaller and less expensive gear motor can be utilized.
Yet another problem commonly encountered with prior cable controlled door operating systems is the inability to automatically monitor the door's progress while it is being opened. Should the door become jammed or obstructed while it is being opened, the operator may not discover the problem until excess cable has been partially or completely unwound from the take-up drum causing damage and malfunction. As such, there is a need for a monitoring and controlling apparatus for cable-controlled doors wherein the gear motor is automatically stopped without operator intervention when the door becomes jammed while opening and wherein the operator is provided with timely notice of the problem.
SUMMARY OF THE INVENTION
In accordance with the present invention, there is provided an improved design for cable slack eliminators used to eliminate the slack in motorized cables for controlling the opening and closing of doors for autoclave or sterilizer chambers, as well as more customary cable controlled door systems. The apparatus of the present invention is adapted to be used on sterilizer and autoclave door systems wherein the door is suspended and controlled by a cable that has one end thereof connected to a motorized take-up drum while the other end thereof is connected to a means for applying force to the cable such as a slack weight or spring. However, while the unique features of the present invention are particularly adapted for use with the door system described immediately above, it will be understood that some of the features may be employed with other door operating systems using flexible members such as chains or ropes in place of the cable and other devices such as hydraulic or pneumatic cylinders in place of the motorized take-up drum.
The present cable slack eliminating apparatus includes a stop plate that is rigidly attached to the side of the sterilizer or autoclave chamber. A bore is provided through the stop plate that is adapted to freely receive the cable therein. A stop member having a girth that is larger than the diameter of the bore provided in the stop plate is attached to the cable at a location between the slack weight and the stop plate.
Accordingly, to open the door, the reversible gear motor controlling the rotation of the take-up drum is activated to cause the cable to unwind from the take-up drum. The cable is permitted to unwind from the take-up drum until the door reaches a fully open position wherein the gear motor is de-energized. Typically, upon de-activation of the gear motor, an additional length of cable is permitted to unwind from the take-up drum. However, because the cable is free to move in a direction away from the stop plate, the cable is kept taut by the slack weight. In doing so, the stop member is caused to move away from the stop plate a distance that is equivalent to the length of cable that was unwound after the door stops moving. As such, when the gear motor is re-activated, it is afforded an amount of time equivalent to the time needed to wind a length of cable onto the take-up drum that is equivalent to the length of cable extending between the stop member and stop plate before encountering the weight of the door. Thus when compared to gear motors of prior cable systems, the gear motors used with the present invention can be smaller because the torque required at start up is limited to the weight of the slack weight and not the weight of the door.
To close the door, the gear motor rotation is reversed thereby causing the cable to be wound onto the take-up drum. In doing so, the cable is permitted to pass freely through the bore in the stop plate for a short period of time wherein the door does not move and the cable tension is limited to the tension created by the slack weight. However, when the stop member contacts the stop plate, the cable end becomes fixed and the cable tension is that induced by the weight of the door. Consequently, the portion of cable extending between the stop member and the take-up drum continues to accumulate on the take-up drum thus causing the door to slide vertically upward to a closed position. Upon reaching a fully closed position, a sensor switch de-energizes the gear motor.
In yet another embodiment of the present invention, the slack weight is replaced by a coil spring. In particular, one end of the coil spring is attached to the end of the cable that is not attached to the take-up drum. The other end of the spring is then attached to a bracket extending from the chamber. It will be appreciated that when assembled in the above-described manner, the coil spring serves to apply a small force to the one end of the cable as did the slack weight in the previously described embodiment.
According to another embodiment of the present invention, a sensor switch in connection with a timer and a microprocessor may be used to provide the sterilizer operator with an alarm or warning message when the door becomes jammed while opening. In particular, the sensor switch is arranged to detect any vertical movement of the slack weight during the opening process. Analysis of the movement of the slack weight is performed to determine whether the door has jammed during the opening process or whether sensor failure has occurred. The gear motor is automatically deactivated and an appropriate alarm is initiated in response to the foregoing analysis.
Accordingly, the present invention provides solutions to the aforementioned problems encountered when using motorized cables for controlling the opening and closing of autoclave and sterilizer doors. The present invention provides a means for eliminating the slack in the motorized cable without the need for an expensive electro-mechanical brake and gear motor. In addition, the present invention provides a means for automatically monitoring the opening of the door to determine whether it has jammed and, if so, for automatically providing an alarm. These and other details, objects and advantages will become apparent as the detailed description of the present invention proceeds.
BRIEF DESCRIPTION OF THE DRAWINGS
The preferred embodiment of the invention will now be described by way of example only, with reference to the accompanying Figures wherein like members bear like reference numerals and wherein:
FIG. 1 is a front elevational view of the preferred embodiment of the cable slack eliminator of the present invention connected to a sterilizer door system;
FIG. 2 is a side elevational view of the cable slack eliminator and sterilizer door system of FIG. 1;
FIG. 3 is a side view of the cable slack eliminator of the present invention;
FIG. 4 is a cross-sectional view of the stop member of the present invention;
FIG. 5 is a diagrammatic view of a sterilization chamber and the cable slack eliminator of the present invention showing the sterilizer door in the closed or fully up position;
FIG. 6 is a diagrammatic view of the sterilization chamber and cable slack eliminator of FIG. 5 showing the sterilizer door in a partially closed position;
FIG. 7 is a diagrammatic view of the sterilization chamber and cable slack eliminator of FIGS. 5 and 6 showing the sterilizer door in a fully open position;
FIG. 8 is a diagrammatic view of the sterilization chamber and cable slack eliminator of FIGS. 5-7 after the door has reached the open position and an additional amount of cable has been permitted to unwind from the take-up drum;
FIG. 9 is a diagrammatic view of the present invention wherein a coil spring is used to keep the cable taut;
FIG. 10 is a top view of the cable and sensor arrangement of the present invention; and
FIG. 11 is a flow chart illustrating the steps performed by the microprocessor of the door monitoring and alarm system of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings which are for purposes of illustrating the preferred embodiment of the present invention only and not for purposes of limiting the same, the Figures show a cable slack eliminating device generally designated as 10, adapted to remove the slack from a cable 40 used to open and close the door 14 of a conventional sterilization chamber 12. More particularly and with reference to FIGS. 1 and 2, the sterilization chamber 12 is exemplary of typical sterilization chambers having cable-controlled doors, the construction and operation of which are well known in the art. As such, a detailed description of the sterilization chamber 12 need not be set forth herein beyond that which is necessary to understand the present invention. Also, it will be appreciated by those of ordinary skill in the art that the cable slack eliminating device of the present invention may be easily adapted to similar applications wherein it is desirable to remove the slack from motorized cables. In addition, it will be further appreciated that the present invention may be adapted to remove the slack in a variety of flexible door opening members such as, for example, ropes and chains.
As shown in FIGS. 1 and 2, a sterilization chamber 12 having a vertically slidable door 14 attached thereto is supported above the floor level by a stand member 15. The sterilizer door 14 is slidably attached to the open end of the sterilization chamber 12 by door retainer hardware generally designated as 16. More specifically, the door retainer hardware 16 is attached to each side of the sterilization chamber 12 and the stand member 15 to provide a vertical way system wherein the door is free to slide vertically to an open and closed position. The door 14 is moved vertically within the door retainer hardware 16 by a pulley and cable system generally designated as 30.
The pulley and cable system 30 consists of a pair of pulleys 32 that are rotatably fastened to the lower corners of the door 14 and are adapted to receive a cable 40 therein. One end of the cable 40 is attached to a take-up drum 34 that is rotatably attached to the top of the sterilization chamber 12. A reversible gear motor 36, is attached to the take-up drum 34 and supplies the rotational motion necessary to wind the cable 40 onto the take-up drum 34. The opposite end of the cable 40 is attached to a slack-removing weight 39 that is suspended over a third pulley 38 that is rotatably attached to the sterilization chamber 12. Typically, the slack weight 39 is received in a hollow member 37 that is attached to the side of the chamber 12 by clamps 35 and is adapted to restrict the lateral movement of the weight 39 as the door 14 is opened and closed.
A bottom support member 42 is normally attached to the bottom of the door 14 and is adapted to support the door above the floor when the door is in the fully opened position. It will be appreciated that the conventional gear motors generally used in these applications invariably permit the take-up drum 34 to unwind an additional length of cable 40 after the door 14 has reached the fully opened position and the gear motor 36 has been de-energized. Prior devices have utilized an expensive electro-mechanical brake (not shown) to prevent the take-up drum 34 from rotating after the door 14 has reached the fully opened position and the gear motor 36 has been de-energized.
The present invention is adapted to eliminate the above-mentioned cable slack without the need for an expensive electro-mechanical brake while also enabling a smaller gear motor to be utilized. The present invention includes a stop member 46 that is fastened to the cable 40 and is adapted to engage a stop plate 52 that is attached to the side of the chamber 12 via a mounting block 50. As can be seen in FIG. 3, the cable 40 slidably extends through a bore 51 located in the mounting block 50 and a corresponding slot 53 provided in the stop plate 52.
As can also be seen in FIGS. 3 and 4, the stop member 46 preferably has an upper collar portion 48 and a lower portion 47 that is greater in diameter than the width of the slot 53 located in the stop plate 52. The stop member 46 has a bore 49 extending therethrough that is adapted to slidably receive the cable 40 therein. In the preferred embodiment, as shown in FIG. 4, the stop member 46 is rigidly fastened to the cable 40 by crimping the collar portion 48 into the cable 40. It will be appreciated by those of ordinary skill in the art, however, that the stop member 46 may be rigidly attached to the cable 40 by a myriad of known clamping and fastening means. As can further be seen in FIG. 3, the stop member 46 is attached to the portion of cable 40 that extends between the third pulley 38 and the stop plate 52 when the door is in the open or down position.
To simplify the assembly process, in the preferred embodiment, the bore 51 in the mounting block 50 is greater in diameter than the lower portion 47 of the stop member 46 so that the stop member 46 may, during assembly, be inserted through the bore 51 while being attached to the cable 40. Thereafter, the stop plate 52 is then attached to the mounting block 50 via at least two cap screws 54 that are received in threaded bores (not shown) located in the mounting block 50.
When constructed in the above-described manner, the present invention enables the cable 40 to slide unobstructed through the slot 53 in the stop plate 52 and the bore 51 in the mounting block 50 while it is being wound onto the take-up drum 34. The cable 40 will continue to pass through the slot 53 and bore 51 until the stop member 46 contacts the stop plate 52 thereby causing the portion of the cable 40 extending between the stop plate 52 and the take-up drum 34 to support the weight of the door. At this time, the cable 40 is restricted to move only in a direction toward the pulley 38. As such, when the cable 40 is being wound onto the take-up drum 34, it will be held taut by the weight of the door 14 acting on the portion of cable 40 extending between the take-up drum 34 and the stop member 46. Conversely, should a small amount of cable 40 be permitted to unwind from the take-up drum 34, the slack weight 39 will immediately cause the cable 40 to remain taut by causing the cable 40 to move in a direction toward the pulley 38.
An understanding of the operation of the present invention can be gleaned from FIGS. 5-8 wherein, for purposes of clarity, the elements described immediately above are depicted in diagram form. More specifically, FIG. 5 illustrates the door 14 in the fully up or closed position. To achieve the closed position depicted in FIG. 5, the operator starts the gear motor 36 via a starting switch (not shown) which causes the cable 40 to be wound onto the take-up drum 34. Initially, the cable 40 passes freely through the slot 53 and the bore 51, respectively, in a direction towards the take-up drum 34 until the stop member 46 contacts the stop plate 52. Thereafter, the cable 40 continues to accumulate on the take-up drum 34 thus causing the door 14 to slide vertically to the closed position. A sensor switch (not shown) is strategically positioned on the sterilizer 12 to detect when the door 14 has reached the closed position. When the door has reached the closed position, the sensor switch communicates with the gear motor 36 through electrical conductors (not shown) to cause the gear motor 36 to be de-energized. As such, when in the position depicted in FIG. 5, the door is supported by the taut length of cable 40 that extends between the take-up drum 34 and the stop member 46.
FIG. 6 depicts the door 14 in a partially opened position wherein the door 14 is also fully supported by the length of cable 40 that extends between the take-up drum 34 and the stop member 46. FIG. 7 illustrates the door 14 just as it reaches a fully opened position but immediately before the slack weight has begun to move. It will be understood that when in the fully opened position, the door 14 is supported by the support member 42 which extends between the bottom surface of the door 14 and the floor.
FIG. 8 illustrates the present invention after the gear motor 34 has been de-energized and an additional length of cable, generally designated as "A", has been permitted to unwind from the take-up drum 34. It will be understood that the slack weight 39, in cooperation with the pulley 38, serves to keep the cable 40 taut when the additional length "A" of cable 40 is unwound from the take-up drum 34. When the gear motor 34 is reactivated, however, a length of cable 40, corresponding to the length designated as "A", is initially wound onto the take-up drum 34 before the stop member 46 contacts the stop plate 52. As such, the gear motor 36 does not immediately encounter the weight of the door 14 but instead is initially faced with a small load represented by the weight of the slack weight 39.
In yet another embodiment, as illustrated in FIG. 9, a coil spring 90 is substituted for the slack weight 39. In particular, a spring member 90 having the one end thereof attached to a bracket member 92 affixed to the top of the chamber 12 is attached to the end of the cable 40 that is opposite the take-up drum 34. It will be appreciated that when assembled in the above-described manner, the coil spring serves to apply a small force to the one end of the cable as did the slack weight 39.
As can be seen in FIGS. 5-7, during normal door opening operations, the slack weight 39 remains static until the door reaches the fully opened position. However, if the door 14 becomes jammed or obstructed during the opening process, excess cable will be unwound from the drum and thus cause the slack weight to move. Therefore, in another preferred embodiment of the present invention, we employ a slack weight monitoring system, generally designated as 60, to determine whether the door 14 has jammed while being opened. More specifically, a conventional sensor switch 62 is arranged to detect the normal static position of the slack weight 39 and communicate any deviation therein to a conventional microprocessor 64 which, through its control program, determines whether the door 14 has jammed and, if so, provides the operator with an appropriate alarm signal.
The sensor 62 and the micro-processor 64 are exemplary of proximity sensing switches and microprocessors that are well-known in the art. However, those of ordinary skill in the art will recognize that other types of electro-mechanical sensor switches may be used. As such, the construction and operation of the sensor 62 and the microprocessor 64 need not be discussed herein beyond that which is necessary to fully appreciate and understand the present invention.
Referring now to FIGS. 1 and 10, sensor 62 is preferably removably attached to the side of the chamber 12 via a bracket member 63 that permits the sensor 62 to monitor the position of the slack weight 39. In the preferred embodiment, the bracket member 63 is fastened to a stand off member 61 that is preferably bolted to the side of the chamber 12. As further illustrated in FIG. 10, the sensor 62 is connected to the microprocessor 64 by control line 65. The microprocessor 64 is also connected to an alarm generating device such as, for example, a CRT 67 via a control line 66. It will be appreciated, however, that other forms of alarm generating devices such as line printers, light emitting diodes, bells and whistles may also be used. In addition, the microprocessor 64 is also capable of de-energizing the gear motor 36 through control line 68 (See FIGS. 5-8).
In this embodiment, the sensor 62, in conjunction with the micro-processor 64 and the slack weight 39, is used to de-energize the gear motor 36 after the door 14 has reached a fully down or open position. More specifically, when the support member 42 contacts the floor, thus signifying that the door 14 has reached the fully open position, the gear motor 36 continues to unwind cable 40 from the take-up drum 34. The slack weight 39 keeps the cable 40 taut by moving towards the floor. That movement of the slack weight 39 is detected by the sensor 62 which, through control line 65, communicates to the microprocessor 64. The microprocessor 64 thereafter de-energizes the gear motor 36 through the control line 68.
However, to use the proximity sensor 62 and the microprocessor 64 to their fullest advantage and to provide a method of monitoring the operation of the door 14 as it is opened via the cable and pulley system 30 of the present invention, the timing characteristics of the cable and pulley system 30 must first be determined. More specifically, the amount of time required to lower the door 14 from a fully closed position (See FIG. 5) to a fully opened position (See FIG. 7) must be determined. It will be understood that the amount of time "X" referred to above only encompasses the amount of time to elapse from starting the gear motor 36 until the bottom support member 42 that is attached to the door 14 contacts the floor. That amount of time, designated as "X" seconds, can easily be determined by lowering the door 14 and timing its progression with a stop watch. After "X" has been determined, it is entered into the control program of the microprocessor 64.
The operation of the slack weight monitoring system 30 may be implemented as illustrated in the flow chart of FIG. 11. The flow chart begins at step 70 wherein the gear motor 36 is started by an operator controlled switch (not shown). At this time, a conventional timer 72 communicating with microprocessor 64 through a control line 71 is also started to time the entire door opening process. It will be understood that "T", as referred to in FIG. 11, represents the amount of time that has accumulated on timer 72 from the time the gear motor 36 was started.
As was discussed above, after the support member 42 contacts the floor, the gear motor 36 continues to unwind the cable 40 from the take-up drum 34 thus causing the slack weight 39 to move. The sensor 62 is arranged to detect this movement of the slack weight 39 and send a signal to the microprocessor 64 to de-energize the gear motor 36. In the preferred embodiment, if the sensor 62 has not detected movement of the slack weight 39 within "X" plus four seconds, we assume that the sensor 62 has failed. It will be appreciated by those of ordinary skill in the art that the amount of time allotted in addition to the normal opening time "X" will vary from system to system depending upon other system variables such as, for example, the speed and temperature characteristics of the gear motor and the manufacturing tolerances of the various system components.
As can be seen in FIG. 11, the micro-processor 64 reads the timer value "T", through known data acquisition techniques, in step 74. The microprocessor 64 then performs an analysis to determine whether "T" is greater than "X" plus four seconds in step 76. If "T" is less than or equal to "X" plus four seconds, the control program will continue with step 78. However, if the microprocessor 64 has determined that "T" is greater than "X" plus four seconds, the control program will proceed to step 86 wherein the gear motor 36 is de-energized by the microprocessor 64 through the control line 68. The control program then proceeds to step 88 wherein the microprocessor 64 sends an appropriate alarm signal to the CRT 67 through the control line 66 indicating sensor failure.
In step 78, the microprocessor 64 performs an analysis to determine whether the sensor 62 still senses the slack weight 39. If the sensor 62 senses the presence of the slack weight 39, the control program returns to step 74. If, however, the sensor switch 62 does not detect the slack weight 39, the control program proceeds to step 80 wherein the gear motor 36 is de-energized through the control line 68. Thereafter, the control program proceeds to step 82.
It will be understood that if the door 14 should jam during the opening process, cable slack will continue to be generated as the gear motor 36 continues to unwind the cable 40 from the take-up drum 34. Consequently, the introduction of that slack causes the slack weight 39 to move in a direction towards the floor. In the preferred embodiment, if the slack weight has moved any time prior to "X" minus two seconds, the door 14 is considered to have jammed. Once again, however, it will be recognized by those of ordinary skill in the art that the "X" minus two seconds value may vary somewhat with the types of components being used and their operating characteristics.
In step 82, the microprocessor 64 performs an analysis to determine whether "T" is less than "X" minus two seconds. If "T" is greater than or equal to "X" minus two seconds, it is assumed that the door 14 has opened properly. However, if "T" is less than "X" minus two seconds, the control program will proceed to step 84 wherein the microprocessor 64 sends an appropriate alarm signal indicating a jammed door condition to the CRT 67 through control line 66.
Should the door become jammed while being opened, the sensor 62 in cooperation with the microprocessor 64 sends an alarm signal to the CRT 67 so the operator may take appropriate corrective action. In addition, the present invention also provides detection means to assure that the gear motor has been properly de-energized after the door 14 has reached the fully opened position.
The present invention addresses the various problems encountered when using prior cable and pulley systems to control doors. The instant invention also provides a method for monitoring the opening of sterilizer doors. However, it will be appreciated that various changes in the details, materials and arrangements of parts which have been herein described and illustrated in order to explain the nature of the invention, may be made by those skilled in the art within the principle and scope of the invention as expressed in the appended claims.
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An apparatus for removing the slack from motorized cables used to control doors on sterilizers and autoclaves without the need for electro-mechanical brakes or oversized gear motors. The apparatus is adapted to be used with a door systems wherein a cable having the one end thereof attached to a motorized take-up drum and the other end thereof attached to a slack removing weight is used control the opening and closing of a door. The apparatus includes a stop plate that is rigidly fastened to the sterilizer or autoclave and a corresponding stop member that is rigidly attached to the cable. The stop plate, in conjunction with the stop member, serve to restrict the movement of the cable in only one direction thus keeping the portion of cable supporting the door taut. When additional cable is unwound from the take-up drum, the slack weight causes the cable to move in a direction away from the stop plate to keep the cable taut. The present invention also affords the gear motor controlling the take-up drum with an amount of time to develop the amount of torque required to lift the door and overcome the inertia of the system. In addition, monitoring means may be added to monitor the movement of the slack weight to determine whether the door has jammed.
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BACKGROUND OF INVENTION
A system and method for producing a stamped part from a progressive die, particularly a stamped part with multiple operations from coil stock material.
Progressive dies used to make stamped parts, particularly metal parts, are in common use today. Stamped parts made from progressive dies are in common use in many industries, such as the automobile industry. These parts include, for example, door bracket members.
One of the uses for stamped metal parts today relates to the formation of cooling conduits in radiators for vehicles. Stamped ring members similar to washers are formed by progressive die stamping processes, and then coated with copper and braised together to form a radiator conduit.
Stamped ring members used for forming radiator conduits should have a thickness and flatness within a certain range of tolerances in order to provide a commercially satisfactory conduit. Ring members which are out of tolerance can cause openings in the conduits causing leaks in the radiator which are unacceptable.
Thus, the need exists for forming stamped metal parts by progressive die stamping systems and methods which are formed to certain configurations and maintained with dimensions within certain tolerances. A need also exists for improved progressive die stamping systems and methods in general.
SUMMARY OF INVENTION
An improved progressive die stamping system and method is provided in accordance with the present invention. The die members are utilized in a stamping (press) machine for forming products from work pieces, such as strips of coiled steel. The die members have conventional alignment mechanisms for maintaining their mating alignment during the stamping process. One or more sets of punch-type members are provided in one of the die members and are used to pierce the ring members. Corresponding mating anvils and openings in the other die member are used to blank the ring members.
A coin punch in that same die member also cuts the outer perimeter around the opening thereby creating the ring. An anvil and biasing mechanism are provided in the second die member in axial alignment with the coin punch member and are used to maintain the desired dimensional thickness and flatness of the ring members that are being formed. The biasing mechanism can be a gas spring member, a mechanical spring member (such as a wavy washer), or the like.
Knockout punch members are also provided for removing the formed product from the work piece. Also, at least one pilot member is provided for indexing the work piece member in the progressive die members. Openings and chutes are also provided for removing the scrap material made by the pierce punch member and for collecting the completed ring members which are removed from the work piece by the knockout punch member.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 schematically illustrates a progressive stamping die, partially in accordance with the present invention.
FIG. 2 is a cross-section of a progressive stamping die in accordance with the present invention.
FIG. 2A is an enlarged view of a portion of FIG. 2 .
FIG. 3 is a perspective showing one of the die members of a progressive stamping die in accordance with the present invention.
FIG. 4 schematically illustrates the second die member of a progressive stamping die in accordance with the present invention.
FIG. 5 is a schematic plan diagram showing a sensor system in accordance with the present invention.
FIGS. 6 and 7 illustrate two embodiments of ring-type members which can be formed with the progressive stamping die in accordance with the present invention.
DETAILED DESCRIPTION
A progressive stamping die partially in accordance with the present invention is illustrated schematically in FIG. 1 and referred to generally by the reference numeral 10 . The progressive die 10 includes an upper or first die member 12 and a lower or second die member 14 . In general, the upper die member 12 includes a plurality of punch members 16 , which are operated by a punch shoe or the like (not shown) when the progressive stamping die 10 is positioned in a stamping (press) machine. The lower die member 14 typically includes a number of openings or chutes 18 which are used for removing scrap or products from the work piece which is passed along the upper surface 20 in between the two stamping die members 12 and 14 .
The progressive stamping die 10 also includes an alignment mechanism which comprises a plurality of postmembers 22 which are attached to the upper die member 12 and a plurality of cup or socket members 24 which are provided as part of the lower die member 14 . Alignment mechanisms of this type are in common use today with progressive stamping dies and no further explanation or description is needed here. Persons of ordinary skill in the art will have applicable knowledge and experience in order to provide alignment mechanisms for progressive stamping dies in accordance with the present invention.
Similarly, hole and piece punch members, such as indicated generally reference numeral 16 in FIG. 1 , are commonly used in progressive stamping die mechanisms and are known to persons of ordinary skill in the art. In the same manner, openings and chute members, such as openings 18 indicated in FIG. 1 are commonly used in progressive stamping dies and do not have to be described in detail herein.
In operation, the progressive stamping die 10 is positioned in a stamping (press) machine between an upper stamping member, such as a punch shoe and a lower stamping member, such as the bed of the stamping press. The upper die member 12 is fixedly secured to the punch shoe, such as by bolts or other mechanical securing mechanisms while the lower die member 14 is physically attached to the bed of the press. In this manner, when the stamping press is operated, the first and second die members are brought together with considerable force. The force of the stamping machine or press causes the punch members to pierce or deform the work piece member positioned on the lower die member in a desired manner.
In a progressive stamping die, the work piece moves across the stamping die from one end to the other in timed steps or stages. At each step or stage, one or more operations are performed on the work pieces, such as forming a curve or configuration of some sort, or forming a piercing operation of some type. Thus, when the work piece exits from the stamping die, it is configurated or formed in a desired manner. In this regard, a work piece can be subjected to progressive stamping dies in succession in order to form completed parts or products.
Although some of the components in FIG. 1 are conventional for progressive stamping dies, FIG. 1 also includes a plurality of biasing mechanisms 30 which are believed to be unique and part of the present invention. These are explained in more detail below.
As indicated above, the present invention is particularly useful in forming stamped metal parts and components that have specified configurations and dimensional tolerances. For example, the present invention is useful in producing accurately dimensioned coined ring members, such as ring member 32 as shown in FIG. 6 . The ring member 32 includes a central opening 34 and an annular ring 36 . The ring member 32 has a specified thickness T. As ring member 32 is used to form conduits in radiators for automobiles and other vehicles, it is necessary to maintain the thickness T within a certain range of tolerances. This means that the ring member 32 has to have a predetermined planar configuration or flatness to it. With the present invention, that planar configuration and flatness can be maintained on a commercially feasible manufacturing basis.
It is to be understood that the present invention can also be used for producing stamped metal parts other than ring members, such as 32 . Another form of stamped metal product which can be made with the present invention is shown in FIG. 7 . Ring member 40 is similar to ring member 32 , in that it has a central opening 42 and an outer square-type annular ring member 44 and also a pre-specified thickness T 2 . Of course, other products and shapes of ring members and the like can be formed with the present invention as would be understood by persons of ordinary skill in the art.
A cross-section of a preferred embodiment of a progressive stamping die in accordance with the present invention is shown in FIG. 2 and indicated generally by the reference numeral 50 . The die 50 has an upper or first die member 52 and a lower or second die member 54 . As shown, each of the die members 52 and 54 are formed of a number of pieces or plate members, although they can be referred to generally as single members since they move and operate as unitary configurations.
The progressive die has a punch shoe 56 which is used to operate the punches in the first die member 52 while the second die member 54 is attached to the bed 58 of the press (stamping machine). A plurality of flange bases 60 are used to support the first die member 52 .
As indicated in FIG. 2 , a series of punch members are provided in the first die member 52 . The punch members include a pierce punch member 70 , a coin punch 72 and a knockout punch member 74 . The work piece member which is moved progressively along the upper surface of the second die member 54 , is indicated by reference numeral 80 . The work piece can be a piece of steel material from a coil. As the work piece 80 moves through the progressive die 50 , the pierce punch member 70 punches out a piece of material 82 and thus forms an opening 84 in the work piece. A pilot member 86 is then moved into position in the opening 84 A in the second step of the progressive stamping process. The pilot member indexes the work piece member in the die 50 so that it is firmly and accurately positioned for subsequent stamping operations.
The coin punch member 72 in the next step of the progressive stamping die process forms the outer periphery configuration of the ring member 32 . In this regard, the distance of travel of the coin punch is only sufficient to pass part way through the thickness of the work piece member 80 . In this manner, only a portion of the work piece member is actually pierced by the coin punch member. The remainder of the exterior perimeter circumference of the ring member 32 is fractured due to the force of the stamping process. An enlarged view of this situation is shown in FIG. 2A .
Once the ring member 32 is fully formed, the knockout punch member 74 is then utilized in the next station in the progressive stamping die process to push out or “knockout” the ring member 32 from the work piece 80 . At this point, as shown in FIG. 2 , the ring member then proceeds into chute 90 where it falls into a collection box or container 92 .
The pieces of material 82 which are punched out of the work piece 80 by the pierce punch 70 proceed along the opening or chute 94 as indicated by the arrow 96 in FIG. 2 and fall into a scrap bin or container 98 .
As conventional with progressive stamping dies, a counter mechanism 100 is provided in order to aid in the progressive stamping die process.
In order to form stamped metal parts, such as ring member 32 of accurate configuration dimensions, biasing mechanism 30 is utilized. The mechanism 30 is positioned in axial alignment with the coin punch member 72 , as shown in FIG. 2 . The biasing mechanism 30 includes a spring member 102 , together with a return pin member 104 , a solid anvil type member (a/k/a “puck”) 106 , a bottoming disk member 108 and a bottoming ring member 110 . The puck member, bottoming disk member and bottoming ring member are preferably made of hardened tool steel and act together as an anvil for the coin punch member in order to accurately stamp and form the product, such as ring member 32 . The spring member 102 is preferably a gas spring mechanism, but also could be a mechanical spring member, such as a wavy spring-type washer, or a disc spring washer, or a series of spring washers.
A gas spring member which can be utilized with the present invention is the “Tanker 2 ” nitrogen gas spring from Teledyne Fluid Systems. Mechanical spring members which can be utilized with the present invention include disc springs from Lamina, Inc.
As shown in FIGS. 2 and 2A , the bottoming disk member 108 mates and meets with shoulder 112 in the second die member 54 . The shoulder prevents the biasing mechanism from raising the anvil or puck member above a predetermined level.
In order to have a more efficient manufacturing operation, preferably a series or sets of punch members are provided in the stamping die so that a plurality of stamped metal products, such as ring members 32 , can be formed as the work piece moves through the die. In this regard, in the embodiment shown and described herein, five ring members 32 are formed. Thus, five sets or series of punch members and corresponding chute members and biasing members are provided.
FIG. 3 is a perspective or schematic view the upper or first die member 52 . As shown, five sets or punch members A, B, C, D, and E, are provided in this embodiment. Each of the sets or series of punch members includes a punch 70 , a pilot member 86 , a coin punch member 72 , and a knockout punch member 74 . In this manner, when the work piece member, such as work piece 80 , travels from the first end 52 A of the progressive stamping die 50 to the second end 52 B, five ring members 32 are formed per unit of surface area and deposited into the parts compartment 92 .
A plan or elevational view of the second or lower die member 54 is shown in FIG. 4 . Five corresponding sets of openings and other members, A″, B″, C″, D″ and E″, are provided in order to meet and mate with the sets or series of punch members A, B, C, D, and E, respectively. These include a scrap chute member 94 , and a part chute member 90 . They also include openings 87 for a positioning of the pilot members 86 , which are used to index the work piece member. In this regard, the work piece member 80 is shown in hidden lines in FIG. 4 for reference. The anvil or puck member 106 which are part of the biasing mechanisms 30 are also shown in FIG. 4 .
In order to assist in positioning the work piece member 80 and allow it to progressively accurately slide along the upper surface of the lower die member, several side guide members 120 are provided. The side guide members 120 provide a channel (not shown) between the side guide members 120 and the surface of the die member 54 .
It is also important to maintain the tonnage force of the stamping machine above a predetermined minimum amount in order to provide the requisite thickness and flatness of the stamped metal ring members. For this purpose, a tonnage monitor 15 O is provided on the stamping machine which records the force of each stroke (or “punch”) of the machine. If the tonnage, e.g. 45–53 tons, is below or above the present minimum amount, the stamping process will be stopped. It also possible to use a load cell 16 O for the same purpose.
Another aspect of the present invention is shown in FIG. 5 . A plurality of sensor members S are provided in the lower or second die member 54 in order to ensure completion of some of the steps in the progressive stamping die process and thus prevent damage to the die. In this regard, pairs of sensors are provided at each of the openings of the scrap chutes 94 as well as the part chutes 90 . The sensors S are provided immediately below the surface of the die member 54 and are utilized to sense whether a scrap piece member 82 or a ring member 32 is actually pushed into its corresponding chute. The sensors S are connected by conventional electric conduits 130 to a bus member 140 to an appropriate electrical monitoring control system (not shown).
If one of the sensors S do not indicate that a pierced member 82 or a ring member 32 is actually detached from the work piece member 80 , then the progressive stamping die process is immediately shut down until the situation is corrected.
While particular embodiments of the invention have been shown and described, numerous variations and alternate embodiments will occur to those skilled in the art. Accordingly, it is intended that the invention be limited only in terms of the appended claims.
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A progressive stamping die system and method of operation providing dimensionally accurate flat stamped parts. A biasing mechanism is provided in actual alignment with a coin punch member in order to accurately control the configuration and planar accuracy of the stamped parts being formed.
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BACKGROUND OF THE INVENTION
The invention relates to multihull sailing vessels, and more particularly to catamarans, such as covered by Class 114; subclass 39.
Although the principle of multihulled boats, such as the catamaran and the trimaran, were known, having been used by the Polynesians for a long time, the prevailing opinion appears to be that the single hull sailing vessel is more stable. The common misconception is that the catamaran will more readily capsize, even though a study of boating accidents involving catamarans shows that the common misconception not absolutely correct. Applicant's invention is directed to incorporating within multihulls self-righting means so that the boating public will more readily explore the endless possibilities offered by catamarans and trimarans.
The prior art of the catamaran is fairly well covered in U.S. Pat. 3,370,560 to F. M. Lucht, whih describes a catamaran constructed to facilitate movement of the floats in either direction along their axes.
U.S. Pat. No. 3,860,982 to R. D. Rumsey describes a vehicular trailer which can be converted into a water craft by rotating pontoon floats from above the trailer to an operating position such that the wheels of the trailer are above the water.
It is an objective of Applicant's invention to provide safe, economical, and simple means for righting multi-hulled boats after they have capsized.
It is also an objective of Applicant's invention to provide fail-safe means for righting multi-hulled boats after capsizing.
SUMMARY OF THE INVENTION
The invention relates to multi-hulled boats and more particularly catamarans in which the floats can be positioned at various angles relative to their normal operating positions while the vessel is capsized in order to utilize the principles of buoyancy and altering the center of gravity to right the vessel.
BRIEF DESCRIPTION OF THE DRAWINGS
In order to more clearly point out Applicant's invention, reference is made to the following drawing, in which:
FIG. 1 is a front elevation view of a catamaran employing Applicant's invention.
FIG. 2 is a plan or top view of the catamaran shown in FIG. 1.
FIG. 3 is a simplified drawing of a capsized catamaran.
FIG. 4 is a simplified drawing of a catamaran being righted by Applicant's inventive improvements.
FIG. 5 is a simplified drawing of the catamaran more nearly righted than shown in FIG. 4.
FIG. 6 is a simplified drawing of the catamaran shown in FIG. 1.
DETAILED DESCRIPTION
FIGS. 1 & 2 show one embodiment of a catamaran generally indicated as 10 which basically comprises two narrow hulls or floats 12 & 14 held far enough apart by transverse structure 16, 16' & 16" to hold up an efficiently large sail plan (not shown). Mast 18 employs a masthead float 20, which although shown as a "ballcock", any of the other types would work as well. It is noted that although a vessel employing a mast is illustrated, flotation means incorporated within any superstructure over the transverse interconnecting structure would function in the same fashion.
Pivotal means 22, 22' & 22" for changing the position of floats 12 & 14 relative to center of gravity of the vessel as well as to each other comprises mechanical actuating means such as described in U.S. Pat. No. 3,860,982 ganged to be operated from a remote position, although only hinges are illustrated. The pivotal means 22, 22' & 22" may be operated in discrete steps so as to provide some control over the righting of the vessel. The pivotal means 22, 22' & 22" may be incorporated on or within the transverse structures 16, 16' & 16" respectively. Although Applicant's embodiments show interconnecting transverse structure, Applicant's invention applies to any structure for interconnecting floats 12 & 14, such as combinations of webbing and rigid structure. Pivotal means 22, 22' & 22" could also be employed in such other transverse structure. The outlined floats 12' & 14" show alternateposition of floats 12 & 14.
FIG. 3 illustrates a capsized catamaran, the ballcock flotation device 20 on the top of the mast preventing the vessel from completely overturning. FIG. 4 shows the employment of Applicant's invention by the movement of float 12 ninety degrees clockwise from its normal operating position. Movement of float 12 changes the center of gravity and therefore the buoyancy of the vessel so as to right the vessel; lifting the mast out of the water as shown in FIG. 5. Although not illustrated, float 14 may also be moved so as to further aid the righting of the capsized catamaran. When the vessel has been righted as shown in FIG. 5, float 12, and float 14 if moved, may be moved back to their normal operating positions, as shown in FIG. 6.
Obviously, had the catamaran capsized with float 14 floating on the water, movement of float 14 would be in the same manner as described above in the steps for moving float 12, except that movement would be in the counter-clockwise direction.
Although only one embodiment of Applicant's invention has been illustrated, Applicant's invention, applicable to all multihulled vessels, is not to be so limited, but is to be limited only by the breadth and scope of the annexed claims:
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A multihull sailing vessel comprising a plurality of floats having ganged pivotal positioning means incorporated within transverse interconnecting members so that the floats may be rotated around longitudinal axes for righting the vessel whenever it is capsized.
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BACKGROUND OF THE INVENTION
[0001] Over the past thirty years, the potential and observed dangers of heavy metal bearing materials and waste exposure to humans and the environment has been the basis of extensive regulatory control. The leaching and transport of heavy metals into surface water bodies and groundwater is a grave concern because of the danger that the drinking water supplies and the environment will become contaminated. Heavy metal bearing materials and wastes, such as soils contaminated with industrial or commercial products or waste, paint residues, sludge, sediments, foundry dusts, casting sands, steel mill dusts, shredder residues, wire insulation, refuse incinerator flyash, incinerator bottom ash, scrubber residues from air pollution control devices such as cyclones, electrostatic precipitators and bag-house filter bags, may be deemed hazardous by the United States Environmental Protection Agency (U.S. EPA) pursuant to 40 C.F.R. Part 261 if containing certain soluble heavy metals above regulatory limits. Any solid waste can be defined as hazardous either because it is “listed” in 40 C.F.R., Part 261 Subpart D or because it exhibits one or more of the characteristics of a hazardous waste as defined at Part 261, Subpart C. These characteristics are: (1) ignitability, (2) corrosivity, (3) reactivity, and (4) toxicity as tested under the Toxicity Characteristic Leaching Procedure (TCLP).
[0002] 40 C.F.R., Part 261.24(a), contains a list of contaminants and their associated maximum allowable concentrations. The inorganic list includes As, Ag, Ba, Cd, Cr, Pb, Hg, and Se. If a contaminant, such as arsenic, exceeds its maximum allowable concentration, when tested using TCLP analysis as specified at 40 C.F.R. Part 261 Appendix 2, then the material is classified as hazardous. The TCLP test uses a dilute acetic acid either in deionized water (TCLP fluid 2) or in deionized water with a sodium hydroxide buffer (TCLP fluid 1). Both extracts attempt to simulate the leachate character from a decomposing trash landfill in which the hazardous waste being tested for is assumed to be disposed of in, and thus subject to the acetic acid leaching condition. Waste containing leachable heavy metals is currently classified as hazardous waste due to the toxicity characteristic, if the level of TCLP analysis is above 0.2 to 100 milligrams per liter (mg/L) or parts per millions (ppm) for defined metals. The TCLP test is designed to simulate a worst-case leaching situation, that is leaching conditions which would typically be found in the interior of an actively degrading municipal landfill. Such landfills normally are slightly acidic with a pH of approximately 5+0.5. Countries outside of the US also use the TCLP test as a measure of leachablity such as Taiwan and Canada. Thailand also limits solubility of Cu and Zn, as these are metals of concern to Thailand groundwater. Switzerland regulates management of solid wastes by measuring heavy metals and salts as tested by a sequential leaching method using carbonated water simulating rainwater. Japan, Mexico and the United Kingdom use similar DI water leach tests to measure for heavy metals.
[0003] Additionally, U.S. EPA land disposal restrictions prohibit the land disposal of treated hazardous wastes which leach in excess of maximum allowable concentrations upon performance of the TCLP analysis. The land disposal regulations require that hazardous wastes are treated until the heavy metals do not leach at UTS levels from the solid waste at levels above the maximum allowable concentrations prior to placement in a surface impoundment, waste pile, landfill or other land disposal unit as defined in 40 C.F.R. 260.10.
[0004] Leach test conditions thus include the conditions to which a sludge, ash, waste, material or soil is subjected during dilute acetic acid leaching (TCLP), buffered citric acid leaching (STLC), distilled water, synthetic rainwater or carbonated water leaching (US SPLP, Japanese, UK, Swiss, and USEPA SW-924).
[0005] Suitable acetic acid leach tests include the USEPA SW-846 Manual described Toxicity Characteristic Leaching Procedure (TCLP) and Extraction Procedure Toxicity Test (EP Tox) now used in Canada. Briefly, in a TCLP test, 100 grams of waste are tumbled with 2000 ml of dilute and buffered acetic acid for 18 hours. The extract solution is made up from 5.7 ml of glacial acetic acid and 64.3 ml of 1.0 normal sodium hydroxide up to 1000 ml dilution with reagent water.
[0006] Suitable water leach tests include the Japanese leach test which tumbles 50 grams of composited waste sample in 500 ml of water for 6 hours held at pH 5.8 to 6.3, followed by centrifuge and 0.45 micron filtration prior to analyses. Another suitable distilled water CO2 saturated method is the Swiss protocol using 100 grams of cemented waste at 1 cm3 in two (2) sequential water baths of 2000 ml. The concentration of heavy metals and salts are measured for each bath and averaged together before comparison to the Swiss criteria.
[0007] Suitable citric acid leach tests include the California Waste Extraction Test (WET), which is described in Title 22, Section 66700, “Environmental Health” of the California Health & Safety Code. Briefly, in a WET test, 50 grams of waste are tumbled in a 1000 ml tumbler with 500 grams of sodium citrate solution for a period of 48 hours. The concentration of leached heavy metal is then analyzed by Inductively-Coupled Plasma (ICP) after filtration of a 100 ml aliquot from the tumbler through a 45 micron glass bead filter.
[0008] Of specific interest and concern regarding the present invention is the leaching of total measured Arsenic, commonly in a reduced form as Arsenite (As+3) or the oxidized form as Arsenate (As+5), under TCLP, SPLP, CALWET, DI, rainwater and surface water conditions as well as non-landfill conditions such as open industrial sites, waste storage cells, waste piles, waste monofills and under regulatory tests which attempt to simulate water leaching for determination of hazardousness of any given soil, material or waste.
[0009] The present invention provides a method of reducing the leachability of total As under TCLP, SPLP, CALWET, DI, rainwater and surface water leaching conditions as well as under regulatory water extraction test conditions as defined by waste control regulations in UK, Thailand, Japan, Switzerland, Germany, Sweden, The Netherlands and under American Nuclear Standards for sequential leaching of wastes by deionized water, while maintaining the stabilized material or waste pH between 2.0 and 12.5 as measured under EPA Method 9045C in order to meet local and state landfill pH disposal limitations, and producing a stabilized material or waste suitable for excavator or loader loading, truck unloading and land disposal or reuse spreading and compaction.
[0010] Unlike the present invention, prior art additives have focused on reducing the solubility of arsenic using Portland cement and Portland cement combinations with stabilizing agents to produce a reduced permeability matrix or solid material form which present post-stabilization handling and disposal complications, whereas the present invention use of zero to low dosage cement, cement kiln dust, or lime in combination with heavy metal stabilizers acts to reduce metals solubility without significant reduction of waste permeability and without formation of cement-like non-free flowing stabilized waste.
[0011] U.S. Pat. No. 5,202,033 describes an in-situ method for decreasing Pb TCLP leaching from solid waste using a combination of solid waste additives and additional pH controlling agents from the source of phosphate, carbonate, and sulfates.
[0012] U.S. Pat. No. 5,037,479 discloses a method for treating highly hazardous waste containing unacceptable levels of TCLP Pb such as lead by mixing the solid waste with a buffering agent selected from the group consisting of magnesium oxide, magnesium hydroxide, reactive calcium carbonates and reactive magnesium carbonates with an additional agent which is either an acid or salt containing an anion from the group consisting of Triple Superphosphate (TSP), ammonium phosphate, diammonium phosphate, phosphoric acid, boric acid and metallic iron.
[0013] U.S. Pat. No. 4,889,640 discloses a method and mixture from treating TCLP hazardous lead by mixing the solid waste with an agent selected from the group consisting of reactive calcium carbonate, reactive magnesium carbonate and reactive calcium magnesium carbonate.
[0014] U.S. Pat. No. 4,652,381 discloses a process for treating industrial waste water contaminated with battery plant waste, such as sulfuric acid and heavy metals by treating the waste waster with calcium carbonate, calcium sulfate, calcium hydroxide to complete a separation of the heavy metals. However, this is not for use in a solid waste situation.
[0015] Unlike the present invention, however, none of the prior art solutions were designed to allow specifically for stabilization of arsenic waste while also meeting landfill pH restrictions and forming a free-flowing and permeable stabilized matrix suitable for loading, transport, disposal and reuse without having a cement-like reduced permeability and strength.
SUMMARY OF THE INVENTION
[0016] The present invention discloses an arsenic bearing material or waste stabilization method through contact of material or waste with stabilizing agents including Portland cement, cement kiln dust, lime kiln dust, dolomitic lime, ferric chloride, ferric sulfate, iron chelate, iron oxides, iron powder and combinations thereof which are properly chosen to complement the material or waste constituency and desired free-flowing and permeable material or waste handling characteristics. The stabilizing agents proven effective are provided in both in dry and wet chemical form, and thus can be contacted with heavy metal bearing material either prior to waste production such as in-stream at wastewater facilities producing sludge or in-duct prior to air pollution control and ash collection devices or after waste production in material collection devices or waste piles.
[0017] It is anticipated that the stabilizers can be used for both RCRA compliance actions such that generated wastes or materials from wastewater facilities, furnaces, incinerators and other facilities do not exceed the TCLP hazardous waste criteria under TCLP or CERCLA (Superfund) response where stabilizers are added to waste piles or storage vessels previously generated. The preferred method of application of stabilizers would be in-line within the property and facility generating the heavy metal bearing material, and thus allowed under RCRA as a totally enclosed, in-tank or exempt method of TCLP stabilization without the need for a RCRA Part B hazardous waste treatment and storage facility permit.
DETAILED DESCRIPTION
[0018] Environmental regulations throughout the world such as those promulgated by the USEPA under RCRA and CERCLA require heavy metal bearing waste and material producers to manage such materials and wastes in a manner safe to the environment and protective of human health. In response to these regulations, environmental engineers and scientists have developed numerous means to control heavy metals, mostly through chemical applications which convert the solubility of the material and waste character to a low soluble form, thus passing leach tests and allowing the wastes to be either reused on-site or disposed at local landfills without further and more expensive control means such as hazardous waste disposal landfills or facilities designed to provide metals stabilization. The present invention discloses an arsenic bearing material or waste stabilization method through contact of material or waste with stabilizing agents including Portland cement, cement kiln dust, quicklime, dolomitic lime, lime, lime kiln dust, ferric sulfate, ferric chloride, iron chelate, iron oxide, iron powder and combinations thereof. The stabilizing agents found effective are available in dry, slurry and wet chemical form, and thus can be contacted with heavy metal bearing material prior to waste generation such as in-stream at wastewater sludge producing plants or in-duct prior to air pollution control and ash collection devices or after waste production in collection devices such as hoppers, dump valves, conveyors, dumpsters or waste piles. The stabilizers are applied in a manner to utilize Portland cement and/or cement kiln dust as a heavy metals stabilizing agent and not as a cementing additive, thus allowing stabilized material and waste to remain suitable for fill material or loose handling and to remain permeable thus allowing for transmission of leachate or water flow. The transmission of water flow becomes important an necessary when using the stabilized waste or material as base fill, cover, embankment or engineered fill, thus eliminating damming or leachate production perched water table effects.
[0019] It is anticipated that the stabilizers can be used for both RCRA compliance actions such that generated materials from mining operations, wastewater facilities, furnaces, incinerators and other facilities do not exceed appropriate TCLP hazardous waste criteria under TCLP, or used for CERCLA (Superfund) response where stabilizers are added to waste piles or storage vessels previously generated and now regulated under RCRA as a hazardous waste pre-disposal. The preferred method of application of stabilizers would be in-line within the property and facility generating the heavy metal bearing material, and thus allowed under RCRA as a totally enclosed, in-tank or exempt method of TCLP stabilization without the need for a RCRA Part B hazardous waste treatment and storage facility permit(s).
[0020] The use of Portland cement, cement kiln dust, lime kiln dust, quicklime, lime, ferric sulfate, ferric chloride, iron chelate, iron oxide, iron powder and combinations would, as an example, provide various amount of cement, cement kiln dust, lime kiln dust, lime, ferric chloride, ferric sulfate, iron chelate, iron oxide, iron powder and or combination contact with material or waste. The cement, cement kiln dust, lime kiln dust, lime, ferric chloride, ferric sulfate, iron chelate, iron oxide, iron powder and combination type, size, dose rate, contact duration, and application means could be engineered for each type of heavy metal bearing material or waste.
[0021] Although the exact stabilization formation molecule(s) are unknown at this time, it is expected that when heavy metals comes into contact with the stabilizing agent(s), low water and low acid soluble compound(s) begin to form such as a mineral ferric arsenate and ferric substitutes less soluble than the heavy metal element or molecule originally in the material or waste. It also remains possible that modifications to temperature and pressure may accelerate of assist formation of minerals, although such methods are not considered optimal for this application given the need to limit cost and provide for optional field based stabilizing operations that would be complicated by the need for pressure and temperature control devices and vessels.
[0022] Examples of suitable stabilizing agents include, but are not limited to, Portland cement, cement kiln dust, lime kiln dust, ferric sulfate, ferric chloride, calcium oxide (quicklime), dolomitic quicklime, iron chelate, iron oxide, iron powder. The amounts of stabilizing agent used, according to the method of invention, depend on various factors including desired solubility reduction potential, desired mineral toxicity, and desired mineral formation relating to toxicological and site environmental control objectives. It has been found that an amount of certain stabilizing agents such as 10% cement and 2% ferric chloride 30% solution, by weight of waste is sufficient for initial TCLP stabilization to less than RCRA limits. However, the foregoing is not intended to preclude yet higher or lower usage of stabilizing agent or combinations if needed since it has been demonstrated that amounts greater than 15% cement kiln dust and also work, but are more costly. The examples below are merely illustrative of this invention and are not intended to limit it thereby in any way.
EXAMPLE 1
[0023] In this example Arsenic bearing sediment from California was stabilized with varying amounts of stabilizing agents including Iron Powder—20 mesh (IP), Ferric Chloride (FC) 30% solution, Ferric Sulfate 10% (FS) solution, Iron Chelate 3.2% solution (IC), Portland Cement Type 1/11 (PC), and Dolomitic Quicklime (DQ), with zero days of sample curing pre-extraction. Both stabilized and un-stabilized sediment were subsequently tested for STLC extract Arsenic content. Samples were extracted according to CALWET. The leachate was digested prior to analysis by ICP. Cement, lime, iron precipitates and waste mixtures produced free flowing sediment with less than 20 PSI unconfined strength at 3 days curing.
TABLE 1 Stabilizer Dose (%) STLC As (ppm) TCLP As (ppm) Sediment Baseline - CA 13 6.7 10 FS 13 3.2 10 FC 14 3.4 10 IP 2.2 1.2 15 PC + 2 FS 4.5 2.4 15 PC + 2 FC 3.4 1.6 10 DQ + 2 FS 2.4 1.6 10 DQ + 2 FC 2.4 1.2
EXAMPLE 2
[0024] In this example smelter slag from Mexico City was stabilized with quicklime and iron powder with 0 days of sample curing pre-extraction. Both stabilized and un-stabilized slag was subsequently tested for water leachable As. Samples were extracted according to the USEPA method 1312 SPLP. The leachate was digested prior to analysis by ICP. Stabilized slag had less than 10 PSI unconfined strength. Permeability was measured at greater than 10-2 cm/sec.
TABLE 2 Stabilizer Dose (%) SPLP As (ppm) Baseline 1500 50 IP + 10 DQ <0.05
[0025] The foregoing results in Table 1 and 2 readily established the operability of the present process to stabilize As thus reducing solubility, measured leachability and bioavailability. Given the effectiveness of the stabilizing agents in causing combined heavy metals to stabilize as presented in the Table 1 and 2, it is believed that an amount of the stabilizing agents equivalent to less than 5% by weight of heavy metal bearing material or waste should be effective. It is also apparent from the Table 1 and 2 results that certain stabilizing agents and complexing blends are more effective for stabilization.
[0026] While this invention has been particularly shown and described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
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This invention provides a method for stabilization of arsenic bearing materials and wastes subject to acid and water leaching tests or leach conditions by addition of stabilizing agents such that the leaching potential is inhibited to desired levels and the material or waste is free flowing. The resultant material or waste after stabilization is deemed suitable for on-site reuse, off-site reuse or disposal as RCRA non-hazardous waste.
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The present invention relates to a composition and to a process for reducing premature polymerization of readily polymerizable unsaturated monomers containing carboxy, ester or nitrile functionality during monomer manufacturing processes by incorporating therein an effective stabilizing amount of a mixture of two or more nitroxide compounds.
BACKGROUND OF THE INVENTION
It is well known that ethylenically unsaturated monomers like vinyl aromatic compounds, such as styrene, α-methylstyrene, vinyltoluene or divinylbenzene or acrylic monomers, such as acrylonitrile, methacrylonitrile, acrylic acid, methacrylic acid and their esters and amides, or unsaturated esters such as vinyl acetate or unsaturated polyesters have a strong tendency to polymerize when subjected to elevated temperatures. Manufacturing processes for such monomers typically include distillations or handling at elevated temperatures.
Known inhibitors of acrylic monomer polymerization include phenothiazine, hydroquinone monomethyl ether, methylene blue and nitroxides. Phenothiazine, while unable to totally inhibit polymerization of acrylic monomers, is a commonly used co-additive. Recent patents claim phenylenediamines with soluble transition metal salts (U.S. Pat. No. 5,221,764), and aryl N-nitroso compounds (EP 0 522 709 A2) are active in acrylic monomer stabilization. U.S. Patent No. 5,504,243 teaches a ternary mixture of a soluble transition metal salt, nitroso compound and nitroxide are also effective as monomer inhibitors. However, there still remains a need for a compound to improve the stability of acrylic monomers during their processing. The need exists for a stable polymerization inhibitor system which will effectively and safely prevent the premature polymerization of unsaturated acrylate monomers during distillation and other purification processes, particularly if air is absent, and during organic-aqueous phase separations.
As indicated above, it is known that acrylonitrile, acrylic acid, methacrylic acid and their respective esters, which are generically referred to in this application as acrylates, have a tendency to undergo unwanted and premature polymerization at elevated temperatures. The industrial production of acrylates also yields several byproducts from which the desired monomer must be separated. One stage of this purification usually involves the partition of the acrylate between an organic and an aqueous phase. During this purification and subsequent steps, the acrylate can undergo a thermally induced polymerization. This undesired reaction must be limited and hopefully entirely repressed to insure that the reactors, tanks, pipes, etc. used to make, store and transport the monomer remain free or essentially free of high molecular weight polymeric material.
The production of acylic acid usually involves the catalytic gas-phase oxidation of propylene. During the purification processing of the monomer, the reaction stream often undergoes a partition between an organic and an aqueous phase. During this partition, a particular polymerization inhibitor may not partition sufficiently well into each of the two phases where it is needed to prevent the monomer from undergoing premature and unwanted polymerization. The instant invention pertains to the use of a mixture of two or more nitroxides which when used together provide synergistic stabilization efficacy to the acylate monomer during its preparation and purification, especially when it undergoes partition between an organic medium and water or even in a solely organic system.
OBJECTS OF THE INVENTION
One object of this invention is to provide a composition protected from premature polymerization. Another object is to provide a process for inhibiting the premature polymerization of ethylenically unsaturated acrylate monomers during the distillation purification steps by incorporating therein an effective amount of a synergistic mixture of two or more nitroxides.
DETAILED DESCRIPTION
The instant invention pertains to a composition for inhibiting the premature polymerization of an ethylenically unsaturated acrylate monomer which comprises
(a) an ethylenically unsaturated acrylate monomer or mixture of monomers, and
(b) an effective inhibiting amount of a synergistic mixture of two nitroxide compounds.
The unsaturated acrylate monomers include acrylic acid, methacrylic acid, the esters of acrylic and methacrylic acids, and acrylonitrile.
While a wide range of mixtures of nitroxides provide synergistic results, particularly effective are the 1:1 blends of 1-oxyl-2,2,6,6-tetramethylpiperidin-4-ol and either bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) sebacate or 1-oxyl-2,2,6,6-tetra-methylpiperidin-4-yl butyrate; or the 1:1 blend of 1-oxyl-2,2,6,6-tetramethyl-4-acetamido-piperidine and 1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl butyrate.
The synergistic stabilization afforded by the mixture of nitroxides is most pronounced when water is present during the purification steps, but synergism is also seen in solely organic systems as well.
While nitroxide compounds as a general class are effective polymerization inhibitors for a wide variety of monomers including the acrylates, the synergistic increase in stabilization efficacy can be demonstrated by use of a mixture of bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) sebacate and 1-oxyl-2,2,6,6-tetramethylpiperidin-4-ol. While a wide variety of ratios afford synergistic inhibition, a 1:1 mixture appears very effective. Synergism is seen where the weight ratio of the two nitroxides is 10:1 to 1:10; preferably 3:1 to 1:3; and most preferably where the weight ratio of the two nitroxides is between 2:1 and 1:2.
The total concentration of the instant mixture of nitroxides is 1-10,000 ppm; preferably 1-2000 ppm; and most preferably 1 to 1000 ppm, based on the weight of monomer being stabilized.
Mixture of nitroxides useful in this invention are preferably selected from the group consisting of
1-oxyl-2,2,6,6-tetramethylpiperidine,
1-oxyl-2,2,6,6-tetramethylpiperidin-4-ol,
1-oxyl-2,2,6,6-tetramethylpiperidin-4-one,
1-oxyl-2,2,6,6-tetramethyl-4-n-propoxypiperidine,
1-oxyl-2,2,6,6-tetramethyl-4-(2-methoxyethoxy)piperidine,
1-oxyl-2,2,6,6-tetramethyl-4-(2-methoxyethoxyacetoxy)piperidine;
1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl stearate,
1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl acetate,
1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl butyrate,
1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl 2-ethylhexanoate,
1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl octanoate,
1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl laurate,
1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl benzoate,
1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl 4-tert-butylbenzoate,
bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) succinate,
bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) adipate,
bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) sebacate,
bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) n-butylmalonate,
bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) phthalate,
bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) isophthalate,
bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) terephthalate,
bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) hexahydroterephthalate,
1-oxyl-2,2,6,6-tetramethyl-4-allyloxy-piperidine;
1-oxyl-2,2,6,6-tetramethyl-4-acetamidopiperidine;
1-oxyl-2,2,6,6-tetramethyl-4-(N-butylformamido)piperidine;
N,N'-bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)adipamide,
N-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-caprolactam,
N-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-dodecylsuccinimide,
2,4,6-tris- N-butyl-N-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl!-s-triazine
4,4'-ethylenebis(1-oxyl-2,2,6,6-tetramethylpiperazin-3-one),
1-oxyl-2,2,6,6-tetramethyl-4-(2,3-dihydroxypropoxy)piperidine,
1-oxyl-2,2,6,6-tetramethyl-4-(2-hydroxy-4-oxapentoxy)piperidine, and
di-tert-butyl nitroxyl.
The instant invention also pertains to a process of preventing the premature polymerization of an acrylate monomer by incorporating therein an effective synergistic stabilizing amount of a mixture of two nitroxide compounds.
The polymerization inhibitor compositions can be introduced into the monomer to be protected by any conventional method. It may be added as a concentrate solution in suitable solvents just upstream of the point of desired application by any suitable means. In addition, these compounds may be injected separately into the extraction or distillation train along with the incoming feed, or through separate entry points providing efficient distribution of the inhibitor composition. Since the inhibitor is gradually depleted during operation, it is generally necessary to maintain the appropiate amount of the inhibitor in the extraction or distillation apparatus by adding inhibitor during the course of the extraction or distillation process. Such addition may be carried out either on a generally continuous basis or it may consist of intermittently charging inhibitor into the extraction or distillation system if the concentration of inhibitor is to be maintained above the minimum required level.
The polymerization inhibiting compositions of this invention are also well suited for protecting the reboiler sections of a distillation column.
The following examples are meant for illustrative purposes only and are not to be construed as limiting the instant invention in any manner whatsoever.
Several methods to determine the efficacy of potential monomer stabilizers have been reported. One method involves laboratory scale distillations (EP 522,709 A2). The drawback of this method is that it requires a large amount of monomer and requires a detailed interpretation of the results such as a visual ranking of polymer build-up at various places in the distillation system. This method does not allow for a rapid screening of monomer inhibitors.
U.S. Pat. Nos. 5,171,888 and 5,221,461 report a method which involves simply heating a sample of monomeric material with a test stabilizer at a fixed temperature, usually between 80° C. and 150° C. and determining the time to exotherm. A modification of this method is described in U.S. Pat. No. 5,504,243 which uses the fact that poly(acrylic acid) is insoluble in acrylic acid. Thus, the failure time in this test is defined as the time to the formation of a visually observable polymer precipitate in the system. This method gives quick and reproducible results when used with neat acrylic acid or when the acrylic acid is partitioned between toluene and water.
In the Examples three different test methods are employed to determine the effectiveness of the nitroxide mixtures. The method is chosen to simulate different aspects of the purification processes.
METHOD 1
Acrylic acid is distilled to remove any storage stabilizer present. Stock stabilizer solutions (1.5 mg/mL) are prepared in propionic acid. This stock solution is added to the distilled acrylic acid to give a test solution having 5 ppm of total stabilizer. Aliquots of this test solution are then placed into three separate reaction tubes. Each tube is purged with a gas mixture (0.65% oxygen in nitrogen) for ten minutes. The tubes are then sealed and placed in a 110° C. oil bath. The tubes are watched till the appearance of visible polymer formation is observed as a precipitate. Failure times are reported as an average of at least three tubes as seen in Table 1.
METHOD 2
Test solutions are prepared as in Method 1. Aliquots (1 mL) of the test solution are placed into three separate reaction tubes. To each tube is added 0.5 mL of toluene and 0.5 mL of distilled water. Each tube is purged as described in Method 1 and then sealed. The tubes are placed in a 90° C. oil bath and heated till visible polymer is observed as a precipitate. Failure times are reported as an average of at least three tubes as seen in Tables 2 and 3.
METHOD 3
Method 3 is identical to Method 2 except that the test solution contains 2.5 ppm of total stabilizer. Failure times are reported as an average of at least three tubes as seen in Table 4.
TABLE 1______________________________________Stabilization of Neat Acrylic Acid(Method 1)Mixture of Components*(% by weight) Failure TimeA B (minutes)______________________________________none none 5100 0 22075 25 24067 33 33050 50 27533 67 33025 75 295 0 100 210______________________________________ *A is bis(1oxyl-2,2,6,6-tetramethylpiperidin-4-yl)sebacate. B is 1oxyl-2,2,6,6-tetramethylpiperidin-4-ol.
TABLE 2______________________________________Stabilization of Aqueous Acrylic Acid(Method 2)Mixture of Components*(% by weight) Failure TimeA B (minutes)______________________________________none none 30100 0 38075 25 38567 33 57050 50 76033 67 72025 75 710 0 100 600______________________________________ *A is bis(1oxyl-2,2,6,6-tetramethylpiperidin-4-yl)sebacate. B is 1oxyl-2,2,6,6-tetramethylpiperidin-4-ol.
TABLE 3______________________________________Stabilization of Aqueous Acrylic Acid(Method 2)Mixture of Components*(% by weight) Failure TimeB C D E (minutes)______________________________________none none none none 30100 0 0 0 600 0 100 0 0 53050 50 0 0 590 0 0 100 0 80050 0 50 0 950 0 0 0 100 66050 0 0 50 755______________________________________ *B is 1oxyl-2,2,6,6-tetramethylpiperidin-4-ol. C is 1oxyl-2,2,6,6-tetramethyl-4-n-propoxypiperidine. D is 1oxyl-2,2,6,6-tetramethylpiperidin-4-yl butyrate. E is 1oxyl-2,2,6,6-tetramethyl-4-(2-methoxyethoxyacetoxy)piperidine.
TABLE 4______________________________________Stabilization of Aqueous Acrylic Acid(Method 3)Mixture of Components*(% by weight) Failure TimeB D F G (minutes)______________________________________100 0 0 0 375 0 0 100 0 47550 0 50 0 555 0 0 0 100 35550 0 0 50 630 0 100 0 0 335 0 50 50 0 590 0 50 0 50 405______________________________________ *B is 1oxyl-2,2,6,6-tetramethylpiperidin-4-ol. D is 1oxyl-2,2,6,6-tetramethylpiperidin-4-yl butyrate. F is 1oxyl-2,2,6,6-tetramethyl-4-(2-methoxyethoxy)piperidine. G is 1oxyl-2,2,6,6-tetramethyl-4-acetamidopiperidine.
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Ethylenically unsaturated carboxyl monomers, such as acrylic or methacrylic acid or their esters, are protected from premature polymerization during manufacture and storage in the presence or absence of water by the incorporation therein of an effective stabilizing amount of a blend two or more nitroxides. Some of these blends provide synergistic stabilization efficacy much superior to the stabilization results obtained by use of either nitroxide alone.
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REFERENCE TO RELATED APPLICATIONS AND INCORPORATION BY REFERENCE
[0001] This patent specification (1) claims the benefit of provisional applications 60/274,575 filed Mar. 9, 2001 and 60/240,480 filed, (2) is a continuation-in-part of patent application Ser. No. 09/398,611 filed Sept. 17, 1999, which in turn is a continuation of patent application Ser. No. 08/673,255 filed Jun. 28, 1996 and now U.S. Pat. No. 6,006,227, and (3) hereby incorporates by reference said prior applications in their entireties, as though fully set forth herein.
INCORPORATION BY REFERENCE OF MATERIAL ON COMPACT DISC
[0002] This patent specification incorporates by reference the contents of the compact disc attached hereto in duplicate (Copy 1 and Copy 2). Each disc is labeled in accordance with Rule 1.53(e)(6), with the collective names Scopeware 2.0 and Vision 1.0. The date of creation of the files on the disc is Jun. 25, 2001. The computer code on the compact disc was generated from correspondingly named source code. The names of individual files on the disc within these collective names, as well as the size of the individual files, are identified in the list of files attached to the Transmission Letter In Accordance with 37 C.F.R. § 1.52(e)(ii). The contents of the compact disc submitted herewith in duplicate and the contents of the list of files attached to said Transmission Letter are hereby incorporated by reference in this application as though fully set forth herein.
FIELD
[0003] This patent specification is in the field of systems for handling information by computer and more specifically relates to an enhanced system for handling heterogeneous items of information to store, manage, customize, organize and/or deliver such information regardless of its source and type in particularly efficient, easy-to-use, and intuitively understood.
BACKGROUND AND SUMMARY
[0004] Traditional information management systems store and retrieve documents on the basis of attributes such as the name and storage location of a document. This, however, can get very unwieldy in typical usage, as more and more names and locations of documents become a part of the storage and retrieval scheme. Although it is possible in some cases to search or order documents by other attributes, such as content and time of creation or revision, it may still be necessary to specify which file folders, directories, or storage devices to search. If a user no longer remembers how a particular item of information was stored in a traditional system, it may be difficult or impractical to retrieve it efficiently.
[0005] In an effort to alleviate these and other concerns with traditional storage and retrieval systems, and to provide a more effective and natural approach that better fits the way people tend to work with and think of items of information, a new system described herein uses approaches that rely primarily on an intuitive, time-associated way of dealing with information. The system is stream-based in that it creates time-ordered streams of information items or assets, beginning with the oldest and continuing through current and on to future items. An information item or asset in this system can be any type—a file, an email message, bookmark, IRL, memo, draft, scanned image, calendar note, photo, shopping list, voicemail, rolodex or business card, a video clip, etc. When a user tunes in a stream, ordinarily a receding parade of documents appears on the screen. The closest are nearest in time. When a new document arrives, for example when a new email message comes in, it appears at the head of the stream, at the front of the parade. (When a newer message arrives, it steps in front of the parade.) Further-away documents are older.
[0006] Ordinarily, a user stands at the line current in time and looks into the past, but the stream also extends into the future. If the user has a meeting next Tuesday at 10 AM, a note to that effect goes into the stream's future, and a note about a meeting Wednesday goes in the stream in front of the note about next Tuesday. Documents in the stream flow steadily onward, as time does. Documents in the future part of the stream flow toward the present; documents in the present flow toward the past. Newly arriving documents push older documents further into the past.
[0007] The receding parade of documents is an efficient way to present information on a computer screen. The display uses foreshortening for a perspective effect to pack more information into limited space. For easy browsing, when the user touches a document on the screen with the cursor, a summary of that document with a thumbnail vies appears immediately, without requiring clicking or other user action, as a browse card—a dedicated small window besides the receding parade of time ordered documents. The user controls the displayed stream with VCR-type controls, to move forward or back, to go toward or to the beginning or the end of time in the stream, to now, or to any date or time, past or future.
[0008] An item of information in a stream need not be given a name, or a designation of storage location. In a traditional system, a requirement that all documents have names can have implications beyond the necessity of inventing and remembering names. For example, emails may not have names of their own but may need to be stashed inside some other file; to search for an email the user may need to go to this special mail file and search that file. In the system disclosed here, items of information such as emails do not need to be named and can be searched along with any other types of information items.
[0009] Searches in the disclosed system can be by a combination of three methods, search, browse, and time-order.
[0010] Time-order in itself often makes it possible to locate documents. Often the user needs a document that showed up recently, this morning, or two days ago, or at some time that can be pinned down with some degree of accuracy. Time-order together with browsing through the stream (and its glance views) makes it possible to glance quickly through the documents that are from the approximate time of interest and quickly pull out the right one. (While traditional systems can time-order documents it often is difficult to intersperse in the list all recent emails, news updates, bulletin-board postings, URLs and other documents, let alone voicemail messages. Without a browse feature for a stream as disclosed herein, such a list can be of little value, whereas with browse and an all-encompassing stream that gets updated promptly with new material, one can sweep over large numbers of documents, get instance glances (summary, thumbnail, etc.) of each and find the right one fast.)
[0011] When searching in a stream in the disclosed system, the user gets a new stream—a substream. One can search on any word or phrase, as every word in every document is indexed, on document types and metadata, and on time-related data (e.g., show me all email from last March). If the user searches for an entity called Schwartz Bottling, the new substream will the narrative or documentary history of all dealings with that entity—first contacts, subsequent internal documents or communications, reports, calendar items, and so on.
[0012] A substream in the disclosed system is in some ways similar to a folder or directory in a traditional system. Instead of a “Schwartz Bottling” folder in which the user has put documents by so naming them, he/she has created a substream with those document, and can save it for later use or create it again as needed. The substream can do all a folder can but is much more powerful than a folder. A substream collects documents automatically; the use r has to put documents in a folder by hand, one by one. A subsream can persist in that it continues to trap newly created or received documents that match it. If a user looks at the “Schwartz Bottling” substream tomorrow, she/he may find it has grown to include a new email or other documents that were interspersed automatically. A substream can tell a story, and include the future. A substream is non-exclusive, in that a document can belong to many substreams. A folder in a traditional system imposes on computers many of the obsolete, irrelevant limitations of a physical filing cabinet drawer or folder. A substream is an organizational tool that can make more efficient use of computer characteristics than an analog of filing an retrieving physical documents.
[0013] One reason for the efficiency of the disclosed system is that it handles all types of different documents, or items of information, in essentially the same way, even if the document is of a type or format unknown to the system. Each document when created, received or otherwise encountered is treated consistently according to a universal Document Object Model (DOM). As described below in more detail, the system processes the document to create its Document Object Modes that includes various aids such as significant information about the document including items such as summary, type of document, thumbnail of the document, who is the document' owner, who has permission to access the document, keywords, command options, time stamp, index, etc. This creation of a document's DOM is done automatically, although the user can aid the process. It can be done by a translator agent or programmatically.
[0014] The system creates a glance view or browse card of each document that has the same overall format to make searching for and working with a document more intuitive but also is specific to the documents in many ways. One important difference from traditional systems is that the browse card has command buttons that match the type of documents. While the command set for traditional systems may use the same command button set for different types of documents, in the disclosed system the command set that shows in the displayed browse card is specific to the document—it has the unique combination of command buttons that make sense for that document. The command buttons unique to the browse card can be shown on the card itself or separately.
[0015] The browse card comes on the screen automatically when the cursor is over the corresponding document in the displayed stream; the user need not take any other action such as clicking on the document or taking an action calling a program that can open or work with the document.
[0016] The universal DOM of a document is created automatically as a new document of any type is added to the basic stream of information items. It is done for any existing, legacy documents, when the system is first installed on a computer, and is done as any additional documents are created or otherwise come in. Metadata such as owner, date, access permission and keywords are created as part of this automatic process.
[0017] Access permission is a part of a document's metadata, so permission levels need have the constraints of traditional information handling systems where a group or an individual typically has access to all documents in a particular folder or directory, or has a particular type of access to a folder.
[0018] Search results are integrated into a substream, at the right place, when and as they become available. The user can start using an incomplete substream and watch it build up. If the search must extend over a number of computers or even servers, and some are unavailable at the time, the results that come in when any become available are integrated into the substream at the right places.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] [0019]FIG. 1 illustrates a screen that can serve as a default view when a software product according to a preferred embodiment is opened on a computer; the labels that are added are not normally a part of the displayed screen.
[0020] FIGS. 2 - 8 are flowcharts illustrating processes in an example of a preferred embodiment.
[0021] [0021]FIGS. 9 and 10 are examples of configurations in a preferred embodiment.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0022] [0022]FIG. 1 illustrates a default screen seen on a PC or other equipment working with the disclosed system. It can show up upon turning on the computer, or upon calling the disclosed system. As seen in FIG. 1, the screen illustrates a receding stream of documents, with the most recent documents at the front. Passing the cursor over a document in the stream causes that document's “glance view” or “browse card” to appear on the screen. The glance view of a document is so labeled in FIG. 1. The screen also includes the following features appropriately labeled in FIG. 1: (a) the Search Field is an area in which the user can type one or more words for which the system will search in documents (information assets) in the displayed part of the stream and/or in additional information assets that might not be displayed; (b) the Main Menu is where the user sets preferences, finds help information, logs out, and/or performs other operations; (c) the Header contains information such as links, command buttons and choice boxes used to navigate; (d) the Stream View Options allow the user to configure the presentation of the stream of information assets; (e) the Document Glance allows quick scanning of information assets that are visible on the screen, and presentation of more detailed information on the selected information asset; (f) the Type Glyphs identify the nature of an information asset at a glance (e.g., a Word document); and (g) the Thumbnails is a graphic representation of the type of document (e.g., an audio file, an email, an event, etc.). The User Guide published by the assignee hereof (a copy is submitted concurrently with the filing of this application with an IDS form) further describes the operation of a relevant example and, together with the programs contained in the compact disc submitted herewith, provides a more detailed disclosure of a preferred embodiment.
[0023] Certain particularly novel features of the disclosed system are described below by reference to flowcharts and block diagrams. More detailed information on a particular example of implementation of these and other features of the system are evident from the software on the attached compact disc, which is the best mode known to the inventors at the time of filing this patent application.
[0024] [0024]FIG. 2 illustrates creation of a universal data object model of a documents in accordance with a preferred embodiment. This is an important part of the disclosed system that helps make possible the efficient handling of heterogeneous document types in a manner that users find easy and intuitive. A document object model (DOM) can be thought of as a document shell of the information asset (IA) that contains, anon other items, a thumbnails of the information asset, permission rights, and metadata. The DOM is created from the IA and is stored in a desktop computer and/or a server, either independently of the IA itself or with a replica (copy) of the IA. From there, the system makes the DOM (with a pointer to its IA or replicated IA) to the desktop user or to users that have access to the document through some computer connection.
[0025] As seen in FIG. 2, the process of creating a DOM starts with the uploading at step S 201 of information assets (documents) through a browser or a client software application, or step S 202 with uploading using a software application agent called Doc Feeder in a specific embodiment of the disclosed system. At the following steps, which need not be performed in the order of their description below, a DOM of the IA is created. The IA uploaded at step S 201 or S 202 can comprise structured or unstructured data At step S 203 the process determines the content type of the IA, e.g., if it is a type that the system recognizes. If it is, the system includes content-type specific metadata in the document's DOM: MIME/content type information, a glyph of the application that creates/views the content-type, and/or the system assigns other content-type data to the DOM shell. If step S 203 determines that the IA is an unknown content type, it assigns to the DOM a content-type for “unknown content-type.” Step S 204 extracts text from the information asset, for example, in a text document, this step extracts the text of the document. Step S 205 extracts text that may not be within but may be associated with the information asset, for example, the time stamp of the document, the owner of the document, and possibly other textual information that is or can be associated with the document. Other possible examples are attributes of the IA such as file reference path, database/repository path, file metrics such as size, encryption, other identification information, etc. Step S 206 generates a thumbnail picture of the IA. The thumbnail can be a reduced-size picture of the document, for example of the first page, and can be converted to a graphic image format. Other examples of thumbnails are JPEG, MPEG, BMP, GIF, AVI, or other still or moving image files representative of some aspect of the IA. Step S 207 produces an automatic summary of the IA, e.g., a replica of its first 500 words, or first 10 sentences, or some other information copied or otherwise derived from the IA. Step S 208 creates a permission list unique to the IA that defines the owner of the IA (e.g., its creator), and lists of people or entities and groups that can access the IA or the DOM of that IA for reading and/or writing purposes. This permission list can be defined by the user for the particular IA or for a class of IAs, or can be created automatically, e.g., by software agents called Doc Feeder or Crawling agent in a particular embodiment of the described system, or by programmatic mapping such as LDAP, Active Directory, NTDS or some other mapping. Alternatively, at least for some documents, the permission list can be default setting.
[0026] Step S 209 assigns keywords to the information asset. The software agents Doc Feeder or Crawler can assign keywords, and the user can manually assign or add keywords. Step S 210 generates and assigns to the IA a Globally Unique Document ID, e.g. as 64 bit code unique to the IA. Step S 211 determines and assigns to the IA document operations that are unique to the IA. Depending on the IA, these operations or command buttons can be basic, such as “View” and “Reply.” They can be content-specific, such as “Play” for multimedia information assets. They can be solution-specific, such as “Fax” of Purchase.” They can be user-specific, such as “Delete” allowed to only certain users. An important point is that the operations or command buttons assigned to a particular IA match the IA and need not be the same for different information assets, as is the typical case with traditional information management systems. Step S 212 assigns optional operations or command buttons to the IA. They include, for example, commands to send the IA to an optical character recognition (OCR) service that can be a separate service, IP, HTTP-based or an asynchronous operation. Alternatively, the optional operation can be another OCR operation that can perform OCR on a selected part of the IA, or on digital graphic portions or can involve multi-part associations. At step S 213 , the information asset is submitted to an indexing engine (asynchronous service) Again, this can be a separate service, IP, HTTP-based. This step can index all or selected fields of the IA, including but not limited to the IA summary, title, permissions, IA text, keywords, time, metadata, and content-type. At step S 214 the DOM created as described above is submitted to a storage service. This can be a database that is a file reference with a pointer to the actual location of the IA on a network or a local file system, or it can be a database that contains the actual IA in a repository such as a user's computer or a centralized repository. The document object model so generated is made available for use in step S 215 .
[0027] [0027]FIGS. 3 and 4 illustrate methods of creating document object models from information assets. As seen in FIG. 3, three type of information assets are involved—new information assets 301 , modified information assets 301 , and deleted information assets 303 . All come to a file system 304 . At step S 305 , agents specific to the disclosed embodiment of the system known as Scopeware 2.0 translate the IA into a DOM, i.e., create a DOM shell for the IA, with attributes as discussed in connection with FIG. 2. At step S 306 , Scopeware agents translate the IA modifications into an updated DOM and time-stamp the change so the new time-stamp becomes a part of the DOM and the modified IA can be places in the stream of documents at a place reflecting the new time-stamp. At step S 307 , Scopeware agents execute actions for removing the deleted IA from the repository of documents. The display, such as that seen in FIG. 1 reflects the actions takes at steps S 305 , S 306 and S 307 . As a result of step S 305 , the stream on the display shows at 308 the new IA (provided the time period where the new IA fits is being displayed). As a result of step S 306 , the modified IA appears at 309 in its correct place in the displayed receding stream of documents. As a result of step S 307 , the deleted documents is removed at 310 from the displayed stream, and the remaining In FIG. 4, a programmatic information system received new, modified and deleted information assets for storage and distribution to appropriate translation agents as illustrated. In other respects, the FIG. 4 arrangement corresponds to that of FIG. 3, so the description of corresponding portions will not be repeated.
[0028] At least some of the document object model created as described above becomes a part of a glance view or browse card of the type illustrated in FIG. 1. An important feature of the system disclosed here is to conveniently dispaly such a glance view in a natural and intuitively accepted way to facilitate operations.
[0029] Traditional user interfaces for computers typically present lists or graphical icons of “documents” (including but not limited to computer files, emails, web pages, images and other types of electronic information). These lists and icon displays provide only a limited amount of information about the document—typically, title and application type only, although additional information as well in some cases. This can make it difficult for users to identify the document without downloading and/or opening the document with its associated application. For example, in Windows 2000, the user interface displays a small temporary pop-up window of the document's title, application type, author and size when the user hovers his cursor on the document icon; however, the pop-up window appears only after a brief delay, usually 1-2 seconds and is for documents that are on the screen at the time, which tend to be a small part of the many documents typically stored in or accessible through a user's computer.
[0030] In contrast, the disclosed system creates a pop-up window for heterogeneous documents of known and unknown application types that appears instantly, as perceived by the user, as he/she hovers the cursor over the document's representation in the user interface. In the example of FIG. 1, this representation is an index card in a cascading flow of overlapping index cards (called “browse cards”), and the pop-up window is called a “glance view”. This glance view not only contains the document's title, application type and owner, but also may contain rich multimedia cues (such as a thumbnail image of the first page of the document, a WAV or MP3 preview of an audio file, or an animated GIF preview of a video file), text summaries and document operations specific to the document's application type and access permissions. For example, if the user has write permission for a document, the “Edit” operation will be visible and available; however, if not, the Edit operation will not be visible or available. These document operations are interactive, allowing users to select available operations directly.
[0031] Referring to FIG. 5 for an illustration of the instantaneously dynamic, tailored, and interactive document glance view feature of the disclosed system, at S 501 a user hovers his or her computer cursor over a document's browse card. Essentially instantly, at least as perceived by the user, and without any mouse clicking or other action on the part of the user, step S 502 processes the information needed for a glance view to appear on the screen, and at S 503 the glance view appears next to the browse card, using a technology such as Dynamic HTML. If the user clicks on a document's browse card, as detected by the test at step S 504 , and as executed by the user at S 505 , step S 506 causes the glance view to become fixed and step S 507 causes it to remain in the display. The glance view does not change until the user clicks on another document's browse card. If the user does not click on any browse card, as determined by the test of step S 504 , the glance view will instantly change as the user moves his cursor over other browse cards, to reflect the glance view of the underlying browse card. If the user has clicked on a browse card to fix the glance view as a stationary window, the user can then select any of the visible and available document operations, by taking the “yes” branch of step S 508 and selecting at S 509 an available operation (as earlier described, the operations or command buttons that show are specific to the document). At step S 510 the system executes the selected operation (command) and the display reflects this at S 511 . If at step S 508 the user takes the “no” branch, she can continue ro hover the cursor over the stream of browse cards and repeat the process, at step S 512 . If at S 504 the system determines that the user has not clicked to fix a glance view, the glance view information essentially instantly changes at S 513 as the user moves the cursor over other browse cards, and the new glance views appear on the screen at S 514 .
[0032] [0032]FIG. 6 illustrates a process involving another important feature of the disclosed system—granular permissions for access to information assets that allows clients to receive seamless and uniform access to contents without necessitating changes to existing network security and access rights. In traditional systems, a network administrators typically would grant access to specific network drives and file folders. The permission typically would allow a user to access the entire folder or drive, or would deny access to an entire folder or drive, rather than to a particular information asset or document.
[0033] In the disclosed system, each information asset is accessible through specific access permission for each client or designated group of clients. Examples of access stage permissions are read, write, and aware. Read permissions allow a client to view the full information asset. Write permissions allow the client to view and edit the document. Aware permission alerts the client that an information asset exists, for example by providing a document shell in the client's stream of documents, but does not allow the client to view or edit the document. A group of clients who want to collaborate on a project or event can establish a designated group that can be assigned permissions to relvant documents for the project or event. Thus, each member can receive real-time additions to his or her stream of documents and information assets are posted. The clients can assign permission to the other group members themselves, by so designating the appropriate documents to be shared, without involving a network administrator. Some documents, such as personal to-do lists, can be accessible only to a specified user, but the user can change this at any time to allow access, full or partial, to other designated persons. Assignments of permissions for access can be done as granularly as an individual client level or individual document, or as diffuse as a departmental or enterprise level.
[0034] As seen in FIG. 6, an information asset 601 can have permission levels assigned to it in several ways. At step S 602 , a software agent such as Doc Feeder can automatically assign permissions; at step S 603 a programmatic system such as SDAP, Active Directory, Access Control Lists, NT DS, of some other system assigns permissions to the document; and/or at step S 604 the user manually assigns permissions to the document. Examples of processes relevant to different types of permissions are: step S 605 grants access to all public users of the system; step S 606 assigns permissions to groups as illustrated; step S 607 assigns permissions to specific groups as illustrated, and step S 608 freezes permissions and does not allow the document to be changed. The display, of the type illustrated in FIG. 1, can provide information representative of the permissions, as illustrated at steps S 609 thorugh S 612 in FIG. 6.
[0035] Another important feature of the disclosed system is illustrated in FIG. 7 and pertains to integrating search results from distributed searches. In traditional systems, search requests in a client/server model with a central index usually return a single, well-defined results set. In a peer-to-peer network, however, search results may come back to the “Source” computer (the computer that issues the search query) in a haphazard manner because of network latency (variable traffic speed and bandwidth across a distributed network) and variable peer presence (peer computers can be turned on and off, or removed from network at times).
[0036] The disclosed system asynchronous responses to a distributed query across a peer-to-peer network of computers to integrate the results from diverse sources, arriving at different times, and comprising diverse types of documents, into a single unified results set. One preferred embodiment leverages the time-ordered presentation interface earlier described in so that search results are integrated into a time-ordered stream according to each document's original time-stamp, regardless of when the document's search results set was received by the Source computer.
[0037] As seen in FIG. 7, at step 701 a user at a Source computer selects peer computers (“Peers”) across which the distributed search will be performed. If the test at S 703 determines that there is no central registry with peer hookup, and the test at S 704 determines there is no user-specified IP address of peers, the process returns to S 701 , where the user can specify addresses or they can be provided in some other way. The central registry with lookup of Peers can involve Online/offline status, IP/DNS resolution service and Optional public/private key authentication. When the test at S 703 or at S 704 leads to the “yes” branch, at step S 705 the Source computer sends out a search request that travels to each selected Peer in the network. At S 706 , each Peer that receives the search request queries its index for documents that match the search criteria, and at S 707 the peer computer then sends its results set back to the Source computer. The response can be XML-based, a binary byte stream, or an in-band and out-of-band transfer. At S 708 the Source computer takes the results set from each Peer and builds a single collective results set. In a preferred embodiment, this collective results set is organized as a time-ordered stream of documents, as seen in FIG. 1. This can involves an on-the-fly browser combination with XML & XSL with time-sort algorithm, XML to presentation layer with time-sort algorithm, and in-band and out-of-band transfer. Improtantly, at S 709 , the Source computer continues to expand this collective results set, essentially in real time as it receives additional results sets from Peers until all Peers have responded or some other relevant event has taken place. At S 710 , the collective results are displayed as soon as results have come in at the Source computer, and the display is updated as additional results come in, even when a Peer that was off-line comes on line and sends results at a later time.
[0038] Yet another feature of the disclosed system is a particularly convenient tri-state tree. In a single scrolling tree directory of the contents of a hard drive (or hard drives in a network), a user may want to select “Parent Folders” (folders containing subfolders) and “Child Folders” (subfolders contained within a folder) that can be further operated on. This feature allows users to select folders in one or more of the following combinations:
[0039] 1. All Parent Folders and all Child Folders
[0040] 2. Some Parent Folders and all their Child Folders
[0041] 3. Some Parent Folders and some of their Child Folders
[0042] 4. No Parent Folders and no Child Folders (the do nothing option)
[0043] This selection tree has useful application beyond the particular example of information handling disclosed here; it can be used to select folders for any computer operation. For example, it can enable users to discretely select software application or operating system components to install or remove.
[0044] A single scrolling tree directory of Parent and Child Folders that can expand and contract to show the contents of Parent and Child Folders is known —Microsoft Windows Explorer is an example of one. A Tri-State Selection mechanism also is known—Microsoft Add/Remove Windows Components is an example of another way of selecting various Parent and Child Folders. However, the Microsoft Add/Remove Windows Components feature does not display all Parent and Child Folders within a single scrolling tree directory; Child Folder and other contents of a Parent Folder are displayed in a separate window only after the user clicks on a Details button. In addition, only the contents of one Parent Folder can be displayed at a time.
[0045] The Tri-State Selection Tree described here combines the elements of a single scrolling tree directory with a tri-state selection mechanism in a new and unique way to enable users to discretely select specific Parent and/or Child Folders all in one single view.
[0046] Referring to FIG. 8 for an illustration, at step S 801 a user is first presented with a tree directory of the highest level of Parent Folders on a hard drive or network. At S 802 the user can expand the tree directory to show Child Folders by clicking on a plus/minus sign next to each Parent Folder, and the directory so expands at S 803 . At S 804 , the display shows a check box next to each Parent Folder (e.g., to the right of the plus/minus sign). By default, all check boxes are empty, indicating that no Parent or Child Folders are selected. If at step S 805 the user clicks on a check box once, the process at step S 806 selects the marked“/” Parent Folder but none of its Child Folders are selected, and step S 807 shows this on the display. If at step S 808 the user clicks the check box a second time, the slash mark is replaced by an “X” and all the Child Folders' check boxes are then selected and grayed out at S 809 , indicating that all Child Folders are selected for that Parent Folder, and this is displayed at S 810 .
[0047] Thus, by expanding the tree and clicking on check boxes, the user can systematically and efficiently select a discrete number of folders on which to perform an operation.
[0048] Yet another feature of the disclosed system is an arrangement of a redundant array of inexpensive servers (RAIS). Processing of a large set of information or document requires benefits of a centralized architecture—reliability and scalability, and RAIS is a novel approach to provide benefits of a centralized architecture—namely reliability and scalability with numerous inexpensive computers. Thus, RAIS can deliver essentially infinite scalability, can allow inexpensive smaller computers to be used to solve enterprise computational problems rather then expensive larger platforms, cheaper/faster.
[0049] For example, consider:
[0050] Set of Information, D, with specific documents D1, D2, D3; D{D1,D2,D3}
[0051] RAIS of N×N size here with N=3; RowN,ColN
[0052] Replication factor is number of columns
[0053] Scalability factor is number of rows
[0054] 1. Here N=3, with 9 computers
Col1 Col2 Col3 Row1 A A A Row2 B B B Row3 C C C
[0055] 2. To post a Document, Dn, one copy is sent to a sub-server in each ColN, so
Col1 Col2 Col3 Row1 A(Dn) A(Dn) A(Dn) Row2 B B B Row3 C C C
[0056] 3. Thus Dn is replicated N times (N=3) and thus if Col1:Row1 computer is unavailable there are two other computers with the same Dn. This is RAIS replication.
[0057] 4. To post a universe, or set of documents, D{D1,D2,D3}, can use simple (round-robin) or complex (latency, closest path, spanning tree) routing, sending each document to a different RowN.
Col1 Col2 Col3 Row1 A(D1) A(D1) A(D1) Row2 B(D2) B(D2) B(D2) Row3 C(D3) C(D3) C(D3)
[0058] 5. Thus to reassemble the entire universe or set of documents, D, need to send a request to each RowN. To reconstruct, D, for an N×N RAIS requires N request/responses.
[0059] 6. Multiple smaller requests can be used instead of one mammoth request.
[0060] This reduces latency, bandwidth and process constraints. This is RAIS scalability.
[0061] 7. Note that any one of the computers in Row1 can be used to re-construct the total set D found in Col1. For example, if Row :Col1 computer is unavailable, then Row1:Col3 computer has a copy of the data. In fact, D is can be constructed from any arrangement that completes a ColN.
[0062] 8. To increase either replication or scalability simply increase N.
[0063] Scopeware Software Agents, either desktops or servers, can be installed on each computer in a RAIS matrix to achieve this functionality.
[0064] The disclosed system can be implemented in a variety of ways in terms of physical information storage—for example, physical information storage can be centralized or decentralized. Decentralized storage, physical storage of information with multiple servers and/or clients, is possible through network agents called Doc Feeders, which may be located at a server or client level. The Doc Feeder allows a storage location of a client, for example a file folder on a desktop hard drive, to be included in the system level data repository for use throughout an organization or enterprise. Depending upon implementation, the Doc Feeders can replicate the information asset (IA) to a server or maintain a constant pointer to the physical storage location while populating the system with the document object model (DOM). As earlier described, a DOM is a document shell of the IA that contains, among other items, a thumbnail of the IA, permission rights, and metadata. A DOM is created from the IA and placed on the Scopeware server, either independent of the IA or with a replication of the IA. From there, the Scopeware server will share the DOM (with constant pointer to the IA or replicated IA) with other connected system servers and clients in order to make the IA available to all clients connected to the network. Thus, the system servers and network agents (Doc Feeders) act as document proxies for both storage and retrieval of IAs.
[0065] In addition, the system servers within the network need not be physically close in proximity. For example, a client in a truly global organization with locations and system servers on several continents can query and retrieve sales results across all system servers and clients through a federated search. In essence, the disclosed system creates a virtual store from all documents accessible to any system server or client either centralized or decentralized.
[0066] The physical information storage of the disclosed system follows three models: duplication, replication, and document reference. The duplication model physically stores a duplicate IA on the parent Scopeware server that was created by the client. Other clients polling the parent Scopeware server have full access to the IA, depending upon permissions, whether or not the original document is available from its native storage location (i.e. client PC is turned off). The replication model replicates the IA from the parent Scopeware server to the peer Scopeware servers within a federated network. All clients within the federated network have full access to the IA, depending upon permissions, whether or not the original document is available from its native storage location (i.e. client PC is turned off). An example of the replication model is the concept of a redundant array of inexpensive servers. This concept, which is described in detail in the distributed enterprise model, utilizes client machines in place of a singe server. The document reference model “parks” only a DOM of the IA on all Scopeware servers and maintains a constant pointer to the actual physical location of the IA rather than storing a full copy of the IA on the Scopeware server. Other clients will only be able to gain access to the IA when the physical location of the IA is connected to the network (i.e. client PC is turned on).
[0067] There are to primary types of streams in accordance with the disclosed system: Bottom-Up and Top-Down. Through the use of both Bottom-Up and Top-Down methodologies, Scopeware creates a living stream for the client with new DOMs appearing automatically as content arrives. The Scopeware distributed enterprise model can make use of both server-based resources and client-based resources where appropriate. Both types of streams can be used simultaneously and interchangeably.
[0068] Bottom-Up streams are comprised of information collaboration formed by ad-hoc groups of Scopeware clients. A bottom-up stream is composed of information created by the clients of a transitory group. Information shared and created by this group is be replicated via point-to-point connections (i.e. from client PC to client PC). In this way, bottom-up groups can form and disperse frequently, and without notification, while its members will still have access to the shared information. FIG. 9 illustrates this configuration.
[0069] Top-Down streams are more permanent, generally more administrative streams or collections of information, such as company-wide distribution lists, or groups like ‘Accounting’ and ‘Development’. In these groups, information is “parked” to the server from the desktop. The server then sends the information to other known servers. Each client maintains a polling connection to the server to retrieve “parked” documents that have recently arrived from other remote servers or from local clients. FIG. 10 illustrates this configuration.
[0070] As earlier described, the user interface within the Scopeware product portfolio has unique characteristics. The DOM provides certain information that allows quick perusal of the information retrieval results via a proprietary “browse card” or “glance view” which is similar to an index card that contains data on the underlying IA. A unique “browse card” or “glance view” is created for each IA. The “browse card” or “glance view” includes metadata for the document, which is comprised of a title, identification number unique to Scopeware document referencing, date/time stamp, and owner information. The “browse card” or “glance view” also presents a thumbnail image of the IA and a summary of the IA contents. Finally, the “browse card” or “glance view” contains a list of operations appropriate for the IA's application that include, but are not limited to, copy, forward, reply, view, and properties.
[0071] The “browse card” or “glance view” arrives in the stream of those clients that have permission to view the IA. The owner can grant access to other clients or groups by granting read, write, or aware permissions through the properties of the “browse card” or “glance view.” Permission can be granted as granular as an individual-by-individual basis from the DOM, or through predetermined administrative groups via the Scopeware server.
[0072] The “browse card” or “glance view” is presented in a time-ordered sequence starting in the present going back into the past. The “browse card” or “glance view” is available in a number of views. The primary view is the stream. Other formats include a grid, Q, list, and thumbnails. The various views address the client's personal preferences for accessing time-ordered content in their most logical way. These views all contain the information presented in a “browse card” or “glance view” but are organized in a different method. Other specialized views include the address book and calendar.
[0073] An advantage of the “browse card” or “glance view” approach is the ease of browsing, searching, and retrieving IAs. In the stream view, the “browse card” or “glance view” of each IA are aligned much like cards in a recipe box. For each item, the title and application icon are viewable on the “browse card” or “glance view” in the stream. When the client passes over the “browse card” or “glance view” in the stream with the mouse pointer, the full “browse card” or “glance view” is presented to the client for easy viewing. From the “browse card” or “glance view,” the client can perform any of the aforementioned actions available to the IA, subject to permission access.
[0074] The disclosed system is suitable for a number of computing models servicing multiple clients including a single departmental server model, an enterprise server model, a distributed enterprise model, and a peer-to-peer model (absent a dedicated Scopeware server or common server). In addition, the software enables wireless computing independent of or in conjunction with any or all of the aforementioned models. Wireless clients include WAP enabled phones, PDAs, Pocket PCs, and other similarly capable devices capable of receiving and transmitting data across a network. All of the Scopeware Implementation Models make use of the components previously discussed, providing consistent interface available across different computing topologies, from monolithic single servers to peer-to-peer collaboration.
[0075] Access to the IA contained in the Scopeware repository can be achieved through two methods. The first method of access is through the thin-client method. The thin-client method utilizes a web browser, such as Microsoft's Internet Explorer or Netscape's Navigator, on the client device to gain access to the Scopeware repository residing on the Scopeware server. The second method of access is the desktop-client method. The desktop-client method involves a local installation of Scopeware on the client device. The client device is then capable of performing the storage, retrieval, extraction, and processing of IAs as they are introduced to the Scopeware repository. All the models below can utilize either method of access to the Scopeware repository, however the distributed enterprise and peer-to-peer models are optimized with the desktop-client method.
[0076] Single Server Model. A single server model makes content on one Scopeware server available to any client connected to the departmental server. The Scopeware software creates a unique DOM that represents to the user interface the relevant details of the IA physically stored by the server or client. Thus, when a client connected to the network requests access to and retrieval of IAs through Scopeware, the client can view all documents contained within the network that satisfy the query parameters and access restrictions regardless of the document's native application. The documents available include those stored locally by the client, those saved to a central storage location, and those stored by peer clients with Doc Feeders connected to the shared server Enterprise Server Model. In an enterprise server model, where multiple Scopeware servers are installed, federated access to and retrieval of IAs across the network is enabled. In federated information sharing, a client asks one Scopeware server for IAs that may reside on it or one of many connected peer Scopeware servers. In this model, the actual IA may reside on any network-connected client, the Scopeware server, or a centralized data storage location. Transparent to the client, the Scopeware servers shuffle the retrieval request and access restrictions to present a single, coherent stream to the client via the presentation architecture previously discussed (within the original patent document).
[0077] Distributed Enterprise Model. A distributed enterprise model utilizes the clients for storage, retrieval, and processing of IAs. Through the use of directory monitoring agents, similar to network agents, the physical location of an IA need not be on the Scopeware server, but rather can reside with any client. The Scopeware servers take on a secondary role as administration servers and content parking lots. This model pushes the processing tasks to the clients while using the servers to shuttle IAs throughout the enterprise. The indexing engine, thumbnailing engine, lightweight storage database will be based at the clients.
[0078] Taking Scopeware beyond distributed networking and the federated architecture—into a more distributed approach will be straightforward, given the way that the system has been designed. Key elements of the next stage of deployment are distributed document processing and scalable server arrays.
[0079] Distributed document processing consists of two different approaches. First, when information was created physically on a desktop machine, but was part of a larger application and intended for storage on a server (rather than on the desktop), the Desktop facilities could do the document extraction, indexing, thumbnailing, etc., and post the results to the Scopeware Server. Second, a Scopeware Server that was handed a document (perhaps from an OCR process or from a central email application) could hand the document off to an available Scopeware Desktop for the same processing. These strategies relieve the processing load on the Scopeware Server and leave it free to focus on handling searches and stream integration, allowing a given Scopeware Server to handle a much larger user load.
[0080] When an organization needs to support central processing of large document bases—and needs the reliability, accessibility and security of a centralized architecture—Scopeware Servers will support deployment in a novel architecture we have named RAIS—a redundant array of inexpensive servers.
[0081] In this architecture, imagine a square array of desktop machines—call each one a “sub-server.” The array as a whole comprises the Scopeware Server. (This does not require wiring together an actual array or cluster; any interconnect such as a Ethernet sub-net or even HTTP over a broader network will work.) In these arrays, columns of servers provide redundancy for storage, while rows (within columns) provide redundant points of distribution.
[0082] To post document D, one copy of D is sent to a sub-server in each column of the array. To replicate everything five times such that losing any data requires the loss of five sub-servers, five columns are used. The number of columns in the array is managed to support exactly the degree of replication (and redundancy) desired. The write processes can be managed in a number of ways to ensure that the different rows in the columns are balanced.
[0083] To send a polling message or search request (“give me all the latest stuff”), a request is sent to each sub-server in one column (note that the means to do this transparently to the user is an extension of the federated search technology). Each column of sub-servers absorbs one copy of every posting (because any write has gone into at least one row of the column); therefore, all the sub-servers in any one column collectively have copies of everything. Just a “replication factor,” is chosen for data redundancy, a “distribution factor” is chosen for responsiveness and for data management, representing the number of rows in any column. To get ten small responses to a search request instead of one big response, or to distribute the total data-storage burden over ten machines instead of one, the array is implemented with ten sub-servers in every column.
[0084] The entire “Server” can be run with only one row (resulting in replication, but no distribution) or with only one column (resulting in distribution but no replication). In the limit, row size=column size=1, and the effect is to have a single conventional server.
[0085] This approach to distributed processing, scalability and reliability for large applications allows arbitrary sets of “smaller” computers (single/dual processor, inexpensive memory and disk storage) to be used in place of very large, expensive machines. This allows the application platform to be designed to the reliability and access requirements of the particular application, and then scaled incrementally (by adding more small machines into the array) as the actual application grows in terms of users served or information managed.
[0086] Distributed document processing and server arrays will give Scopeware almost infinite scalability while maintaining compatibility with early solutions or architectures. In addition to adding greater reliability, this architecture will support very large information processing applications. This will allow enterprise-scale, top-down applications—inbound support/sales email handling, customer service or even IRS-scale tax document processing.
[0087] Distributed document processing (with Scopeware Desktop) could be combined with either a “conventional” (1 processor array) Scopeware Server or with a more powerful array. This will allow organizations to create departmental or workgroup level solutions that can grow into enterprise applications if necessary.
[0088] At the same time, the system will allow users themselves to create self-organizing applications based on their specific and current needs. Ad hoc teams can create collaborative spaces that cross organizational boundaries if necessary. These applications can leverage either Scopeware Desktops or departmental-level Scopeware Servers.
[0089] Because the system has the architecture and capacity to support any level of centralization or decentralization concurrently, applications and their platforms can be engineered centrally or grown organically, and they can be tailored to the needs of their users and the organization on an ongoing basis.
[0090] Peer-to-Peer Model. The peer-to-peer (P2P) model allows multiple clients to share IA directly without the use of a dedicated Scopeware server. The P2P model allows for pure ad hoc collaboration among Scopeware clients. For example, a client can share IA via the Internet with identified Scopeware clients that have permission to access IA from the client, and vice versa. This is similar to the distributed enterprise environment except the dedicated Scopeware server has been removed as a storage, retrieval, and connection mechanism. Instead, Scopeware clients will connect point-to-point with other Scopeware clients through a general network connection such as the Internet.
[0091] Using P2P, a client can create a virtual shared stream that looks as though it is stored on a server but is in fact stored only by many clients. Historically, all clients would need access to a shared file folder on a common server in order to share information. With Scopeware, clients can share information that is located on each other's device and are not restricted to a common server or single physical storage location. To illustrate, five clients of Scopeware want to create a shared virtual stream to support a project. They call their group “Team One.” Then, when any member of “Team One” posts a document to his or her stream, and marks it “readable by Team One,” the system automatically sends a copy to every Scopeware client on the “Team One” list. Each Scopeware client receiving this document pops it into its client's local stream. Thus information created by a client who is a member of “Team One” (and flagged for Team One by the owner) winds up in the local stream of every member of Team One, whether the post is a document, an event (team meeting), task, or contact. It's as if he had sent his posting to a “client” server, and then everyone had polled the server, but in fact there's no server.
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A steam-based document storage and retrieval system accepts documents that are in diverse formats and come from diverse application, automatically creates document model objects describing these documents in a consistent format and associating time stamps with the documents to automatically create a main stream in chronological order. The stream, or sub-streams meeting selected search criteria, are displayed in a variety of forms, including a receding, partly overlapping stack with aids that facilitate user interaction.
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BACKGROUND OF THE INVENTION
This invention relates to the desulfurization of gases and, in particular, relates to the microbiological disposal of hydrogen sulfide which has been otherwise removed from natural gas.
Natural gas from a well may contain a number of undesirable components which must be reduced to acceptable levels prior to distribution and sale. One of the most common problems in the gas industry is the removal and disposal of hydrogen sulfide. Hydrogen sulfide is an acid gas which is toxic and quite corrosive in the presence of water. Natural gas destined for the fuel market ordinarily must contain no more than 0.25 grains per 100 standard cubic feet or 4 ppm on a volume basis.
The most commercially important treatment system for the removal and disposal of hydrogen sulfide from natural gas consists of a combination of the amine process for removal from the gas stream followed by the Claus process for sulfur recovery. In the amine process, after contacting the gas stream, the amine solvent is heated to 200°-300° F. to liberate H 2 S and regenerate the solvent which is recycled. It is important to note that the H 2 S is removed from the gas stream but that it still must be disposed of. Hydrogen sulfide liberated during regeneration of the amine solvent is converted to elemental sulfur by the Claus process. In the Claus process, one third of the H 2 S of the acid gas stream received from the amine unit is burned with a stoichiometric amount of air to produce sulfur dioxide according to Equation (1). If the entire acid gas stream is fed to the reaction furnace, some conversion of H 2 S to elemental sulfur occurs in the furnace according to Equation (2). Further conversion is achieved by passing the reaction gas through a series of catalytic reactors where elemental sulfur formation proceeds more toward completion at lower temperatures. Alternately, one third of the acid gas stream may be fed to the reaction furnace for complete combustion of H 2 S to SO 2 . The SO 2 is then mixed with the remaining acid gases and fed to the catalytic reactors.
H.sub.2 S+3/2 O.sub.2 →SO.sub.2 +H.sub.2 O+heat (1)
2H.sub.2 S+SO.sub.2 ⃡3S+2H.sub.2 O+heat (2)
The Claus process produces a high quality elemental sulfur product and salvage heat value as process credits which have a significant positive impact on the economics of the process. However, there are inherent limitations and operating problems which may adversely affect the economics of the application of the process to H 2 S disposal. These include the following:
(1) The maximum conversion efficiency with as many as three catalytic reactors in series is only 96-97%. Further treatment of the Claus tail gas may be required to meet local air quality standards.
(2) Conversion efficiency is sensitive to variations in the concentration of H 2 S in the acid gas feed stream.
(3) In the presence of carbon dioxide (CO 2 ) and light hydrocarbons, side reactions can result in the formation of carbonyl sulfide (COS) and carbon disulfide (CS 2 ) in the reaction furnace. The presence of COS and CS 2 may increase the number of catalytic stages requires for adequate H 2 S conversion since COS and CS 2 hydrolysis requires higher temperatures than those which favor conversion of H 2 S to elemental sulfur according to Equation (2).
(4) At H 2 S concentrations of less than 40% the temperature of the reaction furnace is insufficient to result in complete combustion of entrained hydrocarbons in the acid gas stream. Hydrocarbon reaction products can result in deactivation of the catalyst.
(5) Combustion of H 2 S in the reaction furnace becomes more unstable with decreasing concentration of H 2 S in the acid gas feed stream. At very low H 2 S concentrations (less than 20%) preheating of air and acid gas streams is required. In addition SO 2 must be generated by burning recycled elemental sulfur to ensure a proper stoichiometric H 2 S/SO 2 ratio in the feed to the catalytic reactors.
With sufficient H 2 S available, a Claus plant can be profitable and offset other costs associated with natural gas treatment with sulfur sales and recovery of heat values. The break even point is influenced by those factors discussed above. However, because of increasingly stringent air quality standards for sulfur emissions, the Claus process has been applied in many treating situations where it is not economical. A need clearly exists for a new more economical technology in these situations especially with regard to acid gas streams with low concentrations of H 2 S. A new technology which featured a saleable byproduct and greater conversion efficiency could also conceivably displace the Claus process in treating situations where it is presently regarded as economical. (Reference: Kohl, Arthur L. and Fred C. Riesenfeld, Gas Purification, Gulf Publishing Co., Houston, Tex., 3rd Ed., p. 410-421 (1979)).
MICROBIAL REMOVAL OF HYDROGEN SULFIDE FROM A GAS
A number of microbial processes for the oxidation of H 2 S have been described in the foreign patent literature. Those describing water treatment are generally based on the innoculation of wastewaters with Thiobacillus thioparus or other unspecified sulfur bacteria followed by aeration. (Polish Patent No. 98,513, Czechoslovakian Patent No. 178,012, U.S.S.R. Patent No. 1,070,120 and Polish Patent No. 106,991). T. thioparus has also been used to remove H 2 S from a gas which is bubbled through the culture (U.S.S.R. Patent No. 986,469). Mixed cultures of bacteria from the Beggiatoa and Thiothrix genera have been utilized in a similar manner (Japanese Patent No. 57,170,181). Thiobacillus ferroxidans has been used as the basis of two gas treatment processes in which H 2 S is first precipitated as CuS or FeS. The sulfide precipitant is subsequently oxidized by the organism regenerating the precipitating agent (West German Patent No. 3,300,402 and Japanese Patent No. 58,152,488). All of these processes are aerobic. The latter two require a very low, corrosion inducing pH.
A microbial process for the removal of H 2 S from a gas stream based on the photosynthetic bacterium Chlorobium thiosulfatophilum has been proposed as an alternative to the Claus or Stretford process. (Cork, D. J., "Acid Gas Bioconversion--An Alternative to the Claus Process," Dev. Ind. Micro., 23, 379-387 (1982); Cork, D. J. and S. Ma., "Acid Gas Bioconversion Favors Sulfur Production," Biotech. and Bioeng. Symp. No. 12, 285-290 (1982); and Cork, D. J., R. Garunas and A. Sajjad, "Chlorobium limicola forma thiosulfatophilum: Biocatalyst in the Production of Sulfur and Organic Carbon from a Gas Stream Containing H 2 S and CO 2 ," Appl. and Env. Micro., 45, 913-918 (1983)). The process converts H 2 S into a mixture of elemental sulfur and sulfate and claims sulfur and biomass as process credits. However, the requirement for radiant energy is a severe economic disadvantage whether supplied artificially or collected from sunlight.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a method for desulfurizing gases by microbiological techniques. More particularly, the invention involves the use of chemoautotrophic bacteria of the Thiobacillus genus to convert sulfides to sulfates either as a sulfide removal process or as a process for producing biomass. More specifically, the invention involves the use of Thiobacillus denitrificans under essentially aerobic conditions to oxidize sulfur compounds such as hydrogen sulfide to sulfate compounds. A particular embodiment of the invention includes the use of specific strains of Thiobacillus denitrificans which will withstand high sulfide concentrations and be resistant to a common biocide. The process of the invention may be carried out by various techniques such as in a continuous bioreactor system. The invention is particularly applicable to the disposal of H 2 S which has been otherwise removed from natural gas and producing a biomass byproduct.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a flow diagram of the preferred embodiment of the invention.
FIG. 2 is a graph showing the effect of temperature on the growth of Thiobacillus denitrificans.
FIG. 3 is a graph showing the viability of Thiobacillus denitrificans in free suspension in liquid medium without an energy source.
DESCRIPTION OF PREFERRED EMBODIMENTS
Introduction
With the exception of photosynthetic organisms, the majority of the biological world derives energy from the oxidation of organic compounds. However, there exists a group of microorganisms, predominantly bacteria, which may derive metabolic energy and reducing equivalents for biosynthesis from the oxidation of inorganic elements and compounds. These microorganisms may also derive carbon for biosynthesis from an inorganic source such as carbon dioxide. This is termed a chemoautotrophic mode of metabolism. The present invention employs such bacteria and such mode of metabolism in order to remove sulfides from gas streams.
A microbial gas desulfurization process offers several advantages which could make the process commercially viable. These include the following:
1. Direct conversion of hydrogen sulfide to sulfate is possible with no requirement for secondary sulfur recovery.
2. The energy requirements are low since the process operates at ambient or near ambient temperatures.
3. The nutrient is predominantly inexpensive mineral salts resulting in a low cost for chemicals.
4. The pH is moderate so that there are minimal corrosion problems.
5. No hazardous wastes are generated and there are minimal disposal problems.
6. The process produces a high protein biomass and a sulfate salt which could represent salable products.
The ideal microorganism upon which to base a microbial hydrogen sulfide removal process must possess several characteristics in addition to the ability to oxidize hydrogen sulfide. The ideal microorganism would have simple nutritional requirements in order to minimize chemical costs. Preferably the organism would be a strict autotroph, that is, the organism would be capable of deriving all of its metabolic needs from inorganic sources. The ideal organism would also be capable of hydrogen sulfide oxidation in an anaerobic as well as an aerobic environment to give greater versatility to the process. Preferably, the ideal organism would produce a soluble oxidation product from the hydrogen sulfide in order to facilitate separation of the oxidation product from the biomass. The ideal organism would also exhibit a small size and simple morphology so that it can be easily maintained in suspension. Many microorganisms produce an extracellular slime layer or capsid which can cause the microorganisms to adhere to walls and to each other. The ideal organism for hydrogen sulfide removal applications would not produce a capsid in order to prevent problems in transport of the organism. A useful organism would also be able to withstand high pressures and moderately high temperatures. An optimal pH near neutral would be desirable in order to minimize corrosion. And, of course, the ideal microorganism would also exhibit a high rate of hydrogen sulfide oxidation per unit biomass.
Many chemolithotrophic bacteria are capable of utilizing the oxidation of elemental sulfur and reduced or partially reduced sulfur compounds as a source of energy and reducing equivalents. However, taking into consideration the above factors, the bacterium Thiobacillus denitrificans has been discovered to be uniquely suitable for the objects of the present invention.
Thiobacillus denitrificans
Thiobacillus denitrificans (T. denitrificans) was first isolated in 1904 by innoculation of an aqueous medium containing MgCl 2 , K 2 HPO 4 , KNO 3 , Na 2 CO 3 and a sediment of elementary sulfur and CaCO 3 with canal water or mud. A bacterial flora developed which oxidized the sulfur to sulfate and simultaneously reduced nitrate to elemental nitrogen. This was the first evidence of the existence of a chemolithotropic bacterium which could survive in the absence of oxygen. It was subsequently shown that thiosulfate could be substituted for elemental sulfur. It was later demonstrated that a reduced nitrogen source was required for growth and T. denitrificans was cultivated in a defined medium for the first time. (Baalsrud, K. and K. S. Baalsrud, "Studies on Thiobacillus denitrificans," Arch. Mikro., 20, 34-62 (1954)). This achievement led to the first thorough study of the growth characteristics of the bacterium. These same authors reported the following:
(1) T. denitrificans is a facultative anaerobe utilizing oxygen under aerobic conditions or nitrate under anaerobic conditions as terminal electron acceptor.
(2) T. denitrificans is an obligatory autotroph; that is, it cannot derive its metabolic needs from organic sources but is strictly dependent upon elemental sulfur and reduced sulfur compounds as energy sources and carbon dioxide as a carbon source.
(3) Nitrate cannot serve as a sole source of nitrogen. Ammonia nitrogen is required for growth.
(4) Iron is required for growth. Good growth was reported in media containing 0.25-8.3 micrograms Fe/ml.
(5) The optimum pH for growth of T. denitrificans is in the range of 6.2-7.0. The organism is rapidly deactivated below pH 6.0.
Although it has been amply demonstrated that thiosulfate and elemental sulfur may be utilized as energy sources with oxidation to sulfate, the utilization of sulfide as an energy source by T. denitrificans, as well as other Thiobacilli, has been the subject of some controversy in the past. Some investigators have reported that cultures of T. denitrificans provided with sulfide, usually supplied as Na 2 S, as the sole energy source failed to show an increase in protein content or sulfate concentration in batch reactors. Others have observed the oxidation of sulfide by whole cells or cell free extracts of T. denitrificans and other Thiobacilli. The deposition of elemental sulfur in growing cultures has been observed causing some investigators to speculate that sulfide was oxidized to elemental sulfur and thiosulfate purely chemically and that these products were the true substrates for the Thiobacilli. It is now apparent that those investigators who reported that T. denitrificans was incapable of growth on sulfide as an energy source came to an erroneous conclusion due to the very high initial sulfide concentrations used in their experiments (5-8 mM). Soluble sulfide is toxic to Thiobacilli, as well as other microorganisms, in elevated concentrations. It has been demonstrated that T. denitrificans will grow anaerobically on sulfide (Na 2 S) as an energy source if sulfide is used as the growth limiting factor in a chemostat. (Timmer-ten Hoor, A., "Energetic Aspects of the Metabolism of Reduced Sulphur Compounds in Thiobacillus denitrificans," Antonie van Leeuwenhoek, 42, 483-492 (1976)). Under these conditions, the concentration of sulfide in the culture is maintained at very low levels and sulfide is oxidized to sulfate. Although this work established the ability of T. denitrificans to utilize sulfide as an energy source under anaerobic and sulfide limiting conditions, growth on H 2 S under aerobic conditions had not been demonstrated prior to this work.
Growth and Maintenance of Cultures
The routine maintenance of T. denitrificans for stock cultures in a medium containing sulfide as an energy source would require continuous or semi-continuous addition of sulfide in such a way that sulfide did not accumulate to inhibitory levels in the culture but sufficient substrate was made available for growth. Although this could be done within the scope of the present invention, the obvious difficulties associated with routine day-to-day maintenance of cultures in a sulfide medium can be avoided by use of a non-toxic substrate, preferably thiosulfate. A typical thiosulfate maintenance medium is given by Tables 1 to 3.
TABLE 1______________________________________Maintenance MediumComponent per liter______________________________________Na.sub.2 HPO.sub.4 1.2 gKH.sub.2 PO.sub.4 1.8 gMgSO.sub.4.7H.sub.2 O 0.4 gNH.sub.4 Cl 0.5 gCaCl.sub.2 0.03 gMnSO.sub.4 0.02 gFeCl.sub.3 0.02 gNaHCO.sub.3 1.0 gKNO.sub.3 5.0 gNa.sub.2 S.sub.2 O.sub.3 10.0 gHeavy metal solution 15.0 mlMineral water 50.0 ml______________________________________
TABLE 2______________________________________Heavy Metal SolutionComponent per liter______________________________________EDTA (Ethylenediaminetetraacetic 1.5 gacid)ZnSO.sub.4.7H.sub.2 O 0.1 gTrace element solution 6.0 ml______________________________________
TABLE 3______________________________________Trace Element SolutionComponent per liter______________________________________AlCl.sub.3.6H.sub.2 O 0.51 gKI 0.14 gKBr 0.14 gLiCl 0.14 gH.sub.3 BO.sub.3 3.06 gZnCl.sub.2 0.28 gCuCl.sub.2.2H.sub.2 O 0.33 gNiCl.sub.2.6H.sub.2 O 0.51 gCoCl.sub.2.6H.sub.2 O 0.51 gSnCl.sub.2.2H.sub.2 O 0.14 gBaCl.sub.2.2H.sub.2 O 0.16 gNa.sub.2 MoO.sub.4.2H.sub.2 O 0.16 gCuSeO.sub.4.5H.sub.2 O 0.14 gNaVO.sub.3 0.024 g______________________________________
The thiosulfate in the maintenance medium is the energy source, nitrate is the terminal electron acceptor allowing growth in the absence of oxygen, bicarbonate is the carbon source and ammonium is the nitrogen source. The medium also includes a phosphate buffer and sources of various essential mineral nutrients. This maintenance medium is similar to the S-8 medium for Thiobacilli recommended by the American Type Culture Collection except that ammonium chloride has been substituted for ammonium sulfate as the source of reduced nitrogen with an increase in the concentration of ammonium ion, the concentrations of sodium bicarbonate and hydrated magnesium sulfate have been increased and a known source of trace elements has been added.
Oxidation of Hydrogen Sulfide
To produce a culture of T. denitrificans to be utilized for the removal of H 2 S from a gas, the organism is typically grown aerobically in the thiosulfate maintenance medium without nitrate at 30° C. and a pH of 7.0 to an optical density at a wavelength of 460 nanometers (OD 460 ) of approximately 1.0. This optical density corresponds to greater than 10 9 cells per ml. As has previously been indicated, the purpose of this cultivation on thiosulfate is to develop a sufficient concentration of biomass so that hydrogen sulfide can be fed to the reactor at an appreciable rate without exceeding the bio-oxidation capabilities of the biomass. Otherwise, sulfide accumulates in the culture. During growth on thiosulfate an aeration rate of 200 to 300 ml/min/l of culture is used. It is advisable to supplement the air feed with 5% CO 2 to ensure continuous availability of a carbon source.
The pathways for sulfide and thiosulfate oxidation to sulfate in T. denitrificans are not independent but have two common intermediates. In the presence of thiosulfate the rate of sulfide oxidation is reduced because of competition for enzymes of the sulfur pathway. Therefore, there should be no residual thiosulfate in the culture when H 2 S is introduced. This is readily accomplished by cultivating the cells to the point that all thiosulfate has been metabolized. The yield of T. denitrificans biomass on thiosulfate as an energy source has been observed to average 6.7 g dry wt./mole in batch reactors. The desired concentration of biomass can be developed by adjusting the thiosulfate concentration in the medium with the precaution that the medium be thiosulfate limiting. When thiosulfate is depleted, H 2 S may be introduced into the reactor at loadings of 8-10 mmoles/hr/g dry wt. of biomass. The culture must be sufficiently aerated that the reaction does not become oxygen limiting. Oxygen limitation has been observed at bulk oxygen concentrations below approximately 25 μM.
When H 2 S is introduced to a culture of T. denitrificans previously grown on thiosulfate, the H 2 S is immediately metabolized with no apparent lag. Under sulfide limiting conditions, less than 0.001 mM of total sulfide can be detected in the reactor medium. Provided then that the feed gas exits the reactor in equilibrium with the medium, very low levels of H 2 S in the outlet gas can be achieved (less than 1 ppmv). With 10,000 ppm H 2 S in the feed gas at one atmosphere, residence times in the range of 1-2 sec are required if the average bubble diameter is approximately 0.25 cm.
The introduction of H 2 S into a batch T. denitrificans reactor results in the accumulation of sulfate and biomass with a corresponding decrease in the ammonium concentration. No elemental sulfur accumulates in the reactor. The stoichiometry of the reaction in a batch reactor is given by Table 4.
TABLE 4______________________________________Stoichiometry of Aerobic H.sub.2 S Oxidation byT. denitrificans in Batch Reactors.sup.a______________________________________SO.sub.4.sup.-2 /H.sub.2 S 0.99 ± 0.05 mole/moleO.sub.2 /H.sub.2 S 1.81 ± 0.11 mole/moleNH.sub.4.sup.+ /H.sub.2 S 0.10 ± 0.02 mole/moleOH.sup.- /H.sub.2 S 1.75 ± 0.16 equivalents/moleBiomass/H.sub.2 S 4.5 ± 0.9 grams/mole______________________________________ .sup.a 95% confidence intervals
Certain aspects of the stoichiometry of any microbial process are affected by the environment and the growth rate of the microbial cells. During batch growth these parameters are constantly changing. In a continuous stirred tank reactor (CSTR) where a fresh nutrient feed (maintenance medium minus nitrate and thiosulfate) is fed to the reactor at the same rate at which mixed liquor is removed from the reactor, and where there is complete mixing, the environment and growth rate are held constant. Each of these parameters is controlled by the dilution rate at which the reactor is operated. The dilution rate D is defined by Equation (3) where q is the volumetric flow rate of nutrient to the reactor and v is the culture volume.
D=q/v (3)
The stoichiometry of aerobic oxidation of H 2 S by T. denitrificans in a CSTR at dilution rates of 0.053 hr -1 and 0.030 hr -1 is given in Table 5. The yield of biomass was expected to be greater at the higher dilution rate since a greater fraction of substrate H 2 S would be expected to support biosynthesis at higher growth rates. This has been observed to be the case under anaerobic conditions. However, biomass yield from aerobic growth on H 2 S was nearly the same at the two dilution rates investigated.
TABLE 5______________________________________Stoichiometry Of Aerobic H.sub.2 S Oxidation ByT. denitrificans in Continuous Flow Reactors.sup.aDilution Biomass/Rate SO.sub.4.sup.-2 /H.sub.2 S NH.sub.4.sup.+ /H.sub.2 S OH.sup.- /H.sub.2 S H.sub.2 S(hr.sup.-1) (mole/mole) (mole/mole) (eq./mole) (g/mole)______________________________________0.053 1.04 ± 0.06 0.12 ± 0.01 1.77 ± 0.23 7.9 ± 0.70.030 1.06 ± 0.09 0.11.sup.b 2.38.sup.b 8.1 ± 2.0______________________________________ .sup.a 95% confidence intervals .sup.b average of two determinations
It has been reported in the literature that oxygen acts as an inhibiting substrate for T. denitrificans while growing aerobically on thiosulfate. Highest yields of biomass have been observed at low steady state oxygen concentrations in the culture medium. (Reference: Justin, P. and D.P. Kelly, "Metabolic Changes in Thiobacillus denitrificans Accompanying the Transition from Aerobic to Anaerobic Growth in Continuous Chemostate Growth", J. Gen. Micro., 107, 131-137 (1978). As shown in Table 6, experiments have not shown oxygen concentration in the range of 45-150 μM to have a discernable effect on biomass yield for aerobic growth of T. denitrificans on H 2 S.
TABLE 6______________________________________Biomass Yield As A Function of Steady StateOxygen Concentration and Dilution RateDilution Rate [O.sub.2 ] Yield(hr.sup.-1) (μM) (g Biomass/mole H.sub.2 S)______________________________________0.053 45 8.4 60 7.7 150 7.3 130 7.6 150 8.50.030 90 7.7 120 9.0 100 7.5______________________________________
Indications of Upset and Recovery from Upset Conditions
Since H 2 S is an inhibitory substrate, it is imperative that the H 2 S feed rate to a T. denitrificans reactor not exceed the maximum capacity of the biomass for H 2 S oxidation. If the H 2 S oxidation capacity of the biomass is exceeded, sulfide will accumulate in the reactor medium and inhibit the complete oxidation of H 2 S. Reactor upset is first indicated by an increase in the optical density of the culture due to elemental sulfur accumulation. The culture takes on a whitish appearance. This is followed by H 2 S breakthrough. The upset condition is reversible if exposure to the accumulated sulfide is not more than 2 to 3 hours. Reduction in H 2 S feed rate following an upset condition will reduce the H 2 S concentration in the outlet gas to pre-upset levels. In addition, elemental sulfur which accumulated during upset will be oxidized to sulfate upon reduction in H 2 S feed rate. The duration of the upset condition dictates the amount of reduction in the feed rate required for recovery. The more sustained the period of upset, the more reduction in feed rate required. The maximum loading of a T. denitrificans culture will be somewhat dependent upon both the metabolic state (growth rate) of the biomass and the environment of the biomass. Maximum loadings in the range of 16 to 20 mmoles H 2 S/hr/g dry wt. biomass may be expected under aerobic conditions.
Effect of Heterotrophic Contamination
The medium described by Tables 1-3 will not support the growth of heterotrophic microorganisms since there is no organic carbon source. However, if aseptic conditions are not maintained in the operation of a T. denitrificans reactor, heterotrophic contamination will develop in the reactor. T. denitrificans releases organic material into the medium in the normal course of growth or through lysis of nonviable cells. This organic material then supports the growth of heterotrophs. In a T. denitrificans CSTR operated nonaseptically, the concentration of heterotrophic contaminants will level off and remain constant after a time. The steady state concentration of contaminant is not surprisingly dependent upon the concentration of T. denitrificans. Contaminant levels of up to 10% of the T. denitrificans concentration can be expected. Although the presence of a heterotrophic contamination can affect the end use of the biomass product of the process, the contamination does not affect H 2 S oxidation by T. denitrificans.
Characterization of Thiobacillus denitrificans
Other factors pertinent to the operation of a microbial gas desulfurization process include the effects temperature and pressure, the toxicity of other sulfur compounds which may contaminate the feed gas, the effects of accumulating sulfate on cell activity and the effect on viability of maintenance in liquid culture in the absence of an energy source.
Each of these parameters was examined under conditions in which T. denitrificans could be most easily cultured on a small scale, namely anaerobically in thiosulfate maintenance medium. Conclusions reached under these conditions are likely to be pertinent to aerobic growth on H 2 S. As indicated previously, T. denitrificans cells grown on thiosulfate will readily oxidize H 2 S with no lag. It has also been observed that T. denitrifications cells growing on H 2 S can be switched back and forth between aerobic to anaerobic conditions with no apparent lag in either direction. These results indicate that under any of these growth conditions the cells contain basically the same complement of enzymes.
The optimum temperature for growth of T. denitrificans has been reported as 30° C. However, a temperature profile indicating relative growth rates above and below this optimum has not been published. A temperature profile is necessary to predict the effects of a temperature excursion or temperature gradients on overall and local growth rates in a culture. This can be especially important in the case of an inhibitory substrate where a general or localized decrease in growth rate could result in accumulation of the substrate to toxic concentrations. A temperature profile for T. denitrificans ATCC 23642 growing anaerobically on thiosulfate is given in FIG. 2 which indicates optimal growth over a relatively narrow range of temperatures with complete inhibition of growth above 40° C. However, viable counts have shown that at temperatures as high as 45° C., no measurable effect on viability is observed for exposures of up to 5 hours.
Growth of T. denitrificans in thiosulfate medium at 30° C. at elevated pressures indicates that total pressure has no significant effect on growth at pressures of up to 1800 psig N 2 or 1000 psig CH 4 . These results are shown in Table 7. Viability was demonstrated at the conclusion of each test by growth on thiosulfate agar and no heterotropic contamination was indicated in that no growth appeared on nutrient agar. In a microbial gas desulfurization process the microorganisms may be subjected to rapid pressurization-depressurization cycles. Table 8 summarizes the results of rapid pressurization-depressurization at 1250 psig of N 2 on viable count in a culture of T. denitrificans originally grown at that pressure on thiosulfate. Table 8 indicates that repeated pressurization-depressurization has no significant effect on viability.
TABLE 7______________________________________Effect of Pressure on Growth of T. denitrificanson Thiosulfate in Liquid Culture Optical Press. Incubation DensityCulture (psig) Gas Time (days) (460 nm)______________________________________TEST 400 N.sub.2 3 1.10CONTROL 0 3 1.14TEST 600 N.sub.2 4 1.05CONTROL 0 4 1.20TEST 750 N.sub.2 3 0.75CONTROL 0 3 1.20TEST 1000 N.sub.2 3 0.75CONTROL 0 3 1.00TEST 1240 N.sub.2 3 0.75CONTROL 0 3 0.83TEST 1800 N.sub.2 3 1.08CONTROL 0 3 0.87TEST 500 CH.sub.4 3 0.85CONTROL 0 3 0.80TEST 1000 CH.sub.4 3 1.20CONTROL 0 3 0.62______________________________________
TABLE 8______________________________________Effect of Sequential Pressurization-DepressurizationCycles at 1250 psig N.sub.2 on Viability ofT. denitrificans in Liquid CulturePressurization/Depressurization Viable CountCycles (cells/ml)______________________________________0 5.2 × 10.sup.81 3.9 × 10.sup.82 4.2 × 10.sup.83 3.4 × 10.sup.84 4.3 × 10.sup.8______________________________________
Various sulfur compounds common to natural gas are somewhat toxic to T. denitrificans. Those compounds are methyl mercaptan (CH 3 SH), carbon disulfide (CS 2 ), carbonyl sulfide (COS) and dimethyl sulfide (CH 3 SCH 3 ). The order of toxicity to wild type T. denitrificans is CH 3 SH>CS 2 >COS, CH 3 SCH 3 . All are toxic at a partial pressure of 200 mmHg. At partial pressures sufficiently low to be tolerated none are metabolized.
As H 2 S is oxidized by T. denitrificans, a sulfate salt accumulates in the medium. Under aerobic conditions, the counter ion of the sulfate in this salt will be determined by the counter ion of the hydroxide equivalents added to the culture to maintain pH. For example, if KOH is the alkali used for pH control, the oxidation product of H 2 S is primarily present as K 2 SO 4 . Whether the reactor is operated batchwise or on a continuous basis, the concentration of sulfate salt will be dependent upon the rate of H 2 S oxidation per unit volume of culture. The tolerance of T. denitrificans for the accumulating sulfate salt, therefore, has a major influence on the operation of the reactor. Wild type T. denitrificans is tolerant of up to 450 nM K 2 SO 4 when grown anaerobically on H 2 S. Above approximately 500 mM, incomplete oxidation of H 2 S is observed with the accumulation of elemental sulfur and production of N 2 O from incomplete reduction of nitrate. The organism is less tolerant of Na 2 SO 4 ; however, normal reactor operation is observed at Na 2 SO 4 concentrations of 300-400 mM. (NH 4 ) 2 SO 4 causes incomplete H 2 S oxidation at concentrations above 150-200 mM.
As noted above, another factor pertinent to the operation of a microbial gas desulfurization process is the effect on viability of maintenance in liquid culture in the absence of an energy source as would occur if the feed gas to the process were shut off for a period of time. As illustrated by FIG. 3, the viable count in a culture of T. denitrificans decreases with time in the absence of an energy source. However, if a working culture contains at least 10 9 cells/ml, a sufficient number of viable cells will exist after as much as 20 days to provide an adequate innoculum to restart the process if care is taken not to overload the biomass.
Another factor which will influence the economics of a microbial gas desulfurization process is the value of the biomass produced. The protein content of T. denitrificans whole cells grown on H 2 S is 60%±3% by dry weight. This protein content is intermediate between that of soybeammeal (51%) and fish meal. (72%), the two most commercially important sources of bulk protein. The quality of a bulk protein source as a food supplement is dependent not only upon the protein content but also upon the amino acid composition of that protein. Table 9 gives the amino acid composition of T. denitrificans whole cell protein when the organism is grown on H 2 S. Table 10 compares the amino acid composition of T. denitrificans whole cell protein, with respect to the ten essential amino acids in a mammalian diet, to that of soybeam meal and fish meal Table 10 indicates that T. denitrificans whole cell protein, on a g/100 g basis, contains more of nine of these amino acids than soybeam meal. The only possible exception is tryptophan which has not been determined for T. denitrificans protein. Fish meal contains greater quantities of isoleucine, lysine, threonine and possibly tryptophan. The cysteine content of T. denitrificans is so low as to be undetectable. Also pertinent to the nutritional quality of the biomass is the mineral content. A trace element analysis of T. denitrificans biomass grown on H 2 S is given in Table 11.
TABLE 9______________________________________Amino Acid Composition of T. denitrificansWhole Cell ProteinAmino Acid g/100 g Protein______________________________________Alanine 7.8Arginine 7.3Aspartic Acid + Asparagine 10.3Glutamic Acid + Glutamine 11.1Glycine 5.2Histidine 5.5Isoleucine 5.4Leucine 9.7Lysine 7.1Methionine 3.7Phenylalanine 4.4Proline 4.4Serine 3.4Threonine 4.4Tyrosine 3.7Valine 6.7______________________________________
TABLE 10______________________________________Essential Amino Acid Content ofT denitrificans Protein Compared toSoybean Meal and Fish Mean Proteins g/100 g ProteinAmino Acid Soybean Meal Fish Meal T. denitrificans______________________________________Arginine 6.2 6.8 7.3Histidine 2.1 2.8 5.5Isolencine 4.9 6.3 5.4Leucine 6.6 9.4 9.6Lysine 5.6 9.4 7.1Methionine 1.2 3.5 3.7Phenylalanine 4.3 4.3 4.4Threonine 3.3 4.7 4.4Tryptophan 1.2 1.1 --Valine 4.7 6.5 6.7______________________________________
TABLE 11______________________________________Trace Element Analysis of T. denitrificansWhole Cells Grown on H.sub.2 S ppm (wt)______________________________________Fe 7530Zn 140Mg 5800Cu 90Ca 3550Mn 1710Na 3330K 1670Total Ash 12%Total Sulfur 0.9%______________________________________
Mutant Strains
The present invention includes not only the use of wild strains of T. denitrificans such as ATCC 23646 (American Type Culture Collection, Rockville, Md.), but also mutant strains. For example, sulfide tolerant strains of T. denitrificans are desirable to make the proposed microbial gas desulfurization process more resistant to upset from excess H 2 S feed and possibly more tolerant of other sulfur compounds. A biocide resistant strain could provide a means of controlling heterotrophic contamination and therefore produce a microbially pure biomass product without the expense of maintaining aseptic conditions by sterilization of feed streams. Therefore, the term T. denitrificans as used herein and in the claims includes mutants thereof.
Continuous Flow Reactor with Biomass Recycle
A simple CSTR is an economically impractical reactor configuration with respect to volumetric productivity for the proposed microbial gas desulfurization process except where very small amounts of H 2 S are removed. However, a completely mixed, homogeneous environment for the cells is required to avoid localized inhibitory concentrations of sulfide. The most practical reactor configuration presently contemplated for a microbial gas desulfurization process based on T. denitrificans is a CSTR with biomass recycle. Recycle of the biomass allows much higher biomass concentrations to be maintained in the reactor. In addition, with biomass recycle, the hydraulic retention time and biomass retention time are decoupled. Therefore, high dilution rates can be used to replenish the culture medium and control the environment of the cells. Biomass concentration and the quality of the cells' environment will be the two most important variables in maximizing volumetric productivity while maintaining reactor stability. With cell recycle, these two variables are independently controlled.
For a CSTR with biomass recycle, the microbial cells must continuously be harvested from the reactor liquid waste stream. The more common methods of continuous harvesting of microbial cells include continuous centrifugation and tangential flow filtration. An alternative to harvesting and recycle of free cell biomass is the use of an immobilized biomass which is the preferred embodiment of the present invention as will be described hereinafter. If the immobilization matrix is sufficiently dense, biomass from the reactor effluent may be harvested by low gravity sedimentation. An immobilization matrix appropriate for growing cells must allow release of new cells into the surrounding medium. Therefore, the reactor effluent will contain both immobilized cells which could be readily recovered and recycled and free cells. If the free cells are to represent a process credit, they must be recovered. Therefore, even when immobilized cells are utilized, a free cell recovery problem still exists. However, since these cells are not recycled back to the reactor, treatment of the process stream (with a flocculating agent, for example) to improve sedimentation properties can be tolerated.
It was noted previously that a facultative organism offers advantages in versatility in a microbial gas desulfurization process. One of these advantages is revealed in the use of a porous immobilization matrix for the T. denitrificans biomass. Oxygen is only a sparingly soluble gas. At 30° C. and at saturation with air at 1 atmosphere, the concentration of oxygen in the culture medium characteristic of this process is on the order of 200-250 μM. Therefore, the driving force for mass transfer of O 2 into the immobilization matrix is relatively low. Therefore, in a purely aerobic system only the outermost fraction of the matrix volume may be populated with metabolically active cells. Research has shown that T. denitrificans will preferentially use oxygen as an oxidant in the presence of NO 3 - ; however, NO 3 - is immediately utilized when O 2 is depleted. The incorporation of nitrate in the culture medium at concentrations of only a few mM would result in a much higher driving force for mass transfer of NO 3 - into the matrix than O 2 . Therefore, in the presence of a small concentration of NO 3 - the entire void volume of the immobilization matrix could be populated with metabolically active cells. The interior of the matrix would operate anaerobically while the exterior operates aerobically. This is hereafter referred to as a mixed aerobic/anaerobic system. The details of anaerobic metabolism of H 2 S in T. denitrificans have been described in a previous patent application (see U.S. Patent Application Ser. No. 787,219, filed Oct. 15, 1985).
The particular immobilization matrix does not form a part of the present invention and any known matrix material may be used which is suitable for the T. denitrificans. By way of example only, see U.S. Pat. Nos. 4,153,510 and 4,286,061. Also, any suitable procedure well known in the prior art for immobilizing T. denitrificans cells on the matrix material can be used in the present invention as long as the cells may grow and divide while releasing new cells from the matrix.
Referring now to FIG. 1, the immobilized biomass is loaded into the reactor 10 which is filled with maintenance medium without thiosulfate. A limited amount of nitrate may be incorporated in the medium if a mixed aerobic/anaerobic metabolism is desired in the immobilization matrix. The hydrogen sulfide containing gas is passed into the reactor through line 12 and the treated gas with the H 2 S removed flows out line 14. Air is introduced into the reactor through line 11. The maintenance medium and immobilized biomass (the slurry) are stirred by the mixer 16 in order to achieve homogeneity, avoid localized inhibitory concentrations of sulfide and obtain good mass transfer.
Withdrawn from the reactor 10 is a slurry stream 18 which contains partially spent nutrient, free floating bacteria which have been expelled from the immobilizing support material and the dissolved sulfate formed in the reactor during the H 2 S removal process. A form of filtration may be employed to prevent the immobilized biomass from being withdrawn from the reactor along with the slurry. Alternatively, immobilized biomass withdrawn from the reactor along with the slurry is removed from the slurry in separator 20 and recycled to the reactor through line 22. This separator 20, for example, may be a conventional settling basin or hydrocyclone.
The slurry from the separator 20 is then passed to the settler 24 through line 26 to perform the removal of the free cell bacterial biomass. The preferred method of accomplishing this removal is by introducing a flocculating agent as indicated at 28 into the slurry to assist in the agglomeration and settling of the bacterial biomass. The bacterial biomass product is then removed from the settler as indicated at 30. The remaining liquid from the settler 24 now contains the spent nutrient and the sulfate. This liquid is passed through line 32 into the evaporator/fractional crystallizer 34. In the evaporator/fractional crystallizer, the process is controlled depending upon the relative concentrations of the sulfate and the remaining nutrients in the liquid such that only the sulfate is crystallized or such that the crystallized sulfate will contain only that amount of nutrient which has also been crystallized which can be tolerated in the sulfate product depending upon its intended end use. The product from the evaporator/ fractional crystallizer 34 is passed through line 36 to the separator 38 where the crystals are separated from the remaining liquid. The separated crystals containing primarily the sulfate is removed from the settler 38 through line 40. The liquid from the settler 38 contains primarily only the remaining nutrient materials which were present in the withdrawn spent nutrient. This liquid is recycled through line 42 to the reactor 10 along with fresh nutrient introduced through line 44 to replenish the spent nutrient. As shown in FIG. 1, the system for practicing this invention includes a temperature controlling heat exchanger 46 in which the medium being fed into the reactor 10 is controlled to a temperature of about 30° C. if wild type T. denitrificans is utilized or a higher temperature if a temperature tolerant strain is utilized. It may also be advantageous to precondition the makeup medium being introduced through line 44 to the optimal temperature. Further measures which can be employed to control temperature is to precondition the entering gas 12 to the optimal temperature, include a heat exchanger within the reactor 10 and insulate reactor 10.
For the purpose of giving a specific example of the present invention, the treatment of 25×10 6 standard cubic feed/day (7.08×10 8 standard liters/day) of natural gas at 600 psig (42 atmospheres or 4238 kilopascals absolute) containing 1.5 mol % H 2 S will be used. The aerobic process of the present invention could not normally be used to directly remove the H 2 S since the oxygen would contaminate the natural gas. Therefore, a conventional amine plant would be used to treat the natural gas and remove the H 2 S along with CO 2 . The amine plant would remove 1.87×10 4 gram-moles of H 2 S per hour. This H 2 S plus any accompanying CO 2 removed represents the feed stream 12 to the reactor 10. If a stable loading (sulfide limiting conditions) of 10.0 millimols H 2 S per hour per gram biomass is assumed, then 1.87×10 6 g of T. denitrificans biomass will be required to treat the gas stream. With a suitable choice of immobilization matrix, immobilized whole cell reactors can be operated with 40% slurries of porous immobilization beads with low rates of attrition. Furthermore, the beads can develop internal populations of viable cells which pack the beads to 50% of their theoretical packing density. However, to be conservative, a 20% slurry of 200 micron beads with a maximum packing density of 25% of theoretical is assumed. This small bead diameter is selected to minimize internal mass transfer resistances. If a T. denitrificans cell is idealized as a cylinder with a diameter of 0.5 micron and length of 1.5 microns, a 200 micron bead would contain 1.67×10 7 cells at maximum packing. A 20% slurry of beads would therefore contain 1.33×10 14 cells per liter. A viable cell density of 10 9 cells per milliliter is roughly equivalent to 0.5 grams dry weight of biomass per liter. Therefore, a 20% slurry of 200 micron beads with maximum cell packing would contain 67 grams per liter of immobilized cells. To be conservative, 50 grams per liter is chosen as a design basis. Therefore, if the free cell biomass is neglected, a total bubble free culture volume of 3.7×10 4 liters will be required to treat the gas stream described above.
The economics of a microbial gas desulfurization process are obviously strongly influenced by the volumetric productivity of the bioreactor. A second important factor is the dilution rate at which the reactor is operated. Process economics are favored by lower dilution rates. The reactor effluent must be processed to recover biomass and the sulfate salt, both of which may be taken as a process credit. Lower dilution rates result in a lower rate of flow of the effluent stream and increased concentrations of free cell biomass and sulfate which reduce processing costs. In addition, lower dilution rates decrease pumping costs. However, the reduction of dilution rate to improve process economics has a limitation dictated by the tolerance of the biomass for the accumulating sulfate salt in the culture medium. The maximum concentration of the sulfate salt which can be tolerated without significant inhibition of growth, and therefore H 2 S oxidation, will determine the minimum dilution rate at which the reactor can be operated. As noted above, some control can be exerted by choice of the sulfate counter ion which is determined primarily by the hydroxide counter ion in the pH adjusting solution.
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There is disclosed a method for desulfurizing gases by microbiological techniques which involve the use of chemoautotrophic bacteria of the Thiobacillus genus to convert sulfides to sulfates either as a sulfide removal process or as a process for producing biomass. More specifically, the invention involves the use of Thiobacillus denitrificans under aerobic conditions to oxidize sulfur compounds such as hydrogen sulfide to sulfate compounds. The process may be carried out by various techniques such as in a continuous bioreactor system using an immobilization matrix. The method is particularly suited to the disposal of hydrogen sulfide which has been otherwise removed from natural gas and producing a biomass byproduct.
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[0001] This application is a Divisional of U.S. application Ser. No. 14/395,086, filed Oct. 17, 2014, which is a National Stage of International Application No. PCT/AU2013/000390 filed Apr. 16, 2013, claiming priority based on Australian Patent Application No. 2012901499 filed Apr. 17, 2012, the contents of all of which are incorporated herein by reference in their entirety.
[0002] The present invention relates to the field of imaging for physiological, clinical or research applications.
[0003] In one form, the invention relates to dynamic lung function measurement in a human or animal.
[0004] In one particular aspect the present invention is suitable for use in lung function testing for assessing lung function and lung condition.
BACKGROUND ART
[0005] It is to be appreciated that any discussion of documents, devices, acts or knowledge in this specification is included to explain the context of the present invention. Further, the discussion throughout this specification comes about due to the realisation of the inventor and/or the identification of certain related art problems by the inventor. Moreover, any discussion of material such as documents, devices, acts or knowledge in this specification is included to explain the context of the invention in terms of the inventor's knowledge and experience and, accordingly, any such discussion should not be taken as an admission that any of the material forms part of the prior art base or the common general knowledge in the relevant art in Australia, or elsewhere, on or before the priority date of the disclosure and claims herein.
[0006] Lung diseases adversely affect airflow during breathing and alter normal lung motion. Specifically, lung diseases change the elasto-mechanical and aero-resistive properties of the lung which in turn alters the airflow in and out of the lung. For example, interstitial fibrosis increases distal airway stiffness, asthma increases airway resistance and emphysema reduces lung tissue recoil thereby increasing its compliance. Although these diseases differ markedly in both cause and consequence, they all alter the mechanical properties of diseased regions and therefore must also alter motion of these regions.
[0007] Little is known about the dynamics of lung motion during respiration, particularly how different regions of the lung move in relation to other regions during both inspiration and expiration. It is not known whether the lung expands and deflates uniformly, or whether specific regions lead or trail other regions due to differences in local compliances or proximity to the diaphragm. Similarly, it is unknown how diseases affect regional lung motion and whether motion in healthy regions is altered to compensate for diseased regions. Although this information is best provided by imaging the lung in situ, it has not hitherto been possible to image the lung with sufficient spatial and temporal resolution.
[0008] Previous techniques to measure lung motion have relied on the surgical placement of markers, inhalation of contrast agents or removal of the chest wall for imaging.
[0009] Forced Oscillation Technique (FOT) is a very popular and successful global lung function test. FOT works by applying an oscillation to the airway opening and then simultaneously measuring the pressure and flow at the airway opening. FOT determines the impedance of the lungs on a global basis. This technique is popular for determining the state and function of lung tissue non-invasively by measuring the lungs' reaction to a series of input oscillations. Oscillations are generally in the order of 4-48 Hz and as a result any technique to measure the lung response across such a broad range will obviously require very high temporal resolution. For example, U.S. Pat. No. 5,318,038 (Jackson et al) describes an infant respiratory impedance measuring apparatus and method that use FOT.
[0010] One of the drawbacks of this technology is that it cannot measure response locally with in the lungs and as a result it is unable to detect any but the largest physiological changes in the lungs. Due to the global nature of FOT and the potential of destructive interference between different signals in lung regions there is the likelihood that this approach will result in lost information.
[0011] Standard imaging techniques such as X-ray Computer Tomography (CT) and Magnetic Resonance Imaging (MRI) imaging during breath-holds provide little or no information on lung motion and cannot detect disease that cause subtle changes in lung structure. These approaches are particularly limited by the need to image the lung while it is stationary to minimise blurring. In particular, MRI and CT have poor temporal resolution preventing them from being used to image the lungs during a dynamic lung test. Furthermore, due to long acquisition times, both MRI and CT are often used to compare the state of the lung at two different time intervals, usually minutes apart. Interpolation is required to deduce lung motion between two steady state conditions within a breath and such methods assume that the motion follows a linear or defined path. This has obvious drawbacks and limits the ability of the techniques to be used for dynamic lung function testing.
[0012] Clinical gated 4D-CT has also been used for measurement of lung function, including expansion using traditional absorption based imaging at the expense of significant levels of radiation dose. Typically, the phase matching is performed to an accuracy of 7.1% of the breath cycle or 400 ms. This results in poor temporal resolution for investigation for the dynamic patterns of motion and expansion within the lung, particularly for small animal studies.
[0013] Vibration Response Imaging (VRI) is a technology developed for investigating regional lung function and for diagnosis of conditions. US patent application 2007/0244401 relates to a method and system for assessing an interventional pulmonology procedure including VRI imaging. Images indicative of airflow in at least a portion of the respiratory tract are generated from signals indicative of pressure waves at transducers applied to the skin of a subject. Specifically, the signals are measured before and after the interventional pulmonology procedure and used to generate images for comparison. This technique however, suffers from very poor spatial resolution and is based on measurements taken through the chest wall resulting in poor dynamic range of measurements.
[0014] Electrical Impedance Tomography (EIT) is a technique of measuring the impedance through the chest of an electrical signal. EIT provides information through a horizontal slice of the lung, is easily affected by the electrical signals of the heart and has very poor spatial resolution. Typically temporal resolutions of only up to 44 Hz have been used.
[0015] Despite advances in lung imaging, altered patterns of lung motion have not hitherto been utilised for disease detection. Accordingly, there is a need for improved technologies for assessing lung function and diagnosing lung conditions.
SUMMARY OF INVENTION
[0016] An object of the present invention is to provide improved technology for assessing lung function and diagnosing lung conditions.
[0017] Another object of the present invention is to provide an improved method for dynamic lung function testing.
[0018] Another object of the present invention is to provide improved technology for assessing lung function and lung condition in a localised manner.
[0019] Another object of the present invention is to provide a method and apparatus for measuring regional respiratory impedance using forced oscillations.
[0020] A further object of the present invention is to alleviate at least one disadvantage associated with the related art.
[0021] It is an object of the embodiments described herein to overcome or alleviate at least one of the above noted drawbacks of related art systems or to at least provide a useful alternative to related art systems.
[0022] In a first aspect of embodiments described herein there is provided a method for dynamic investigation of a subject lung, the method comprising the steps of:
(i) imparting an oscillation to the lung at one or more forcing frequencies so as to elicit a lung response, (ii) sensing the response of the lung simultaneously with the imparting of the oscillation to elicit a lung response, (iii) choosing at least one parameter used in the sensing to define the lung motion associated with the lung response, (iv) comparing one of the chosen parameters at each forcing frequency with the response at the forcing frequency in at least one region of the lung, and (v) recording the comparison of step (iv).
[0028] Typically the sensing will comprise imaging the response of the lung. Any form of internal or external oscillation may be imparted to the lung—including mechanical input oscillation, an external chest wall oscillation, the heart's oscillation or any other internal bodily oscillation or any other externally applied oscillation.
[0029] Typically the dynamic investigation comprises measurement of respiratory impedance, tissue elasticity or other tissue properties, or any other mechanisms for energy transfer in at least one region of the subject lung.
[0030] The combination of any method of lung imaging with the established ideas of FOT has the potential to provide information provided by FOT but in individual or multiple regions of the image. Established lung imaging systems typically provide at least 2,000 to 1,000,000 or more measures of the lung. This means the combined technique of imaging FOT has an increased richness of up to 1,000,000 times over FOT. Traditional FOT has the drawback in that it is a global measure and as a result is only suited to detecting large physiological changes in lungs. For example, a large physiological change could comprise a moderate change to tissue properties affecting a large portion of the lung. More subtle changes to tissue properties would only be detectable by traditional FOT if they affected a larger portion of the lung, and changes affecting smaller portions of the lung would only be detectable by traditional FOT if they had resulted in a larger affect on local tissue properties.
[0031] In addition FOT testing has the potential to suffer from destructive interference wherein one region of the lung compensates for deterioration in other regions of the lung. More specifically, phase shifts of the forcing frequency can be induced by damping properties of the lungs. Destructive interference is the phenomenon whereby waves that are out of phase cancel each other out and hence this information is lost without any capacity to understand that this has happened. In this situation a global measure would not be sufficient for the detection for the localised deterioration in lung state and/or function.
[0032] The method of the present invention may comprise the additional step (vi) of comparing a parameter between different regions throughout the lung and creating a visual representation thereof.
[0033] The lung responds to an oscillating input to the airway opening via movement of the lung tissue. This movement can potentially reveal detailed information regarding the state and function of the lungs. In the present invention, the oscillation provided to the lung may be of a single frequency, but typically multiple frequencies will be used. The frequencies could be provided simultaneously or one after the other. Oscillations can either be measured at many images per cycle of lowest frequency or an ensemble type average recorded over many cycles, therefore capable of being recorded at a slower rate than the input oscillations.
[0034] Imaging the motion of the lung may be carried out by any suitable method in 1D (single point in the lung), 2D or more preferably 3D, such as MRI, CT, X-ray imaging, and ultrasound or any other suitable form of imaging. A particularly preferred imaging method is phase-contrast x-ray imaging (CTX) as described in Australian patent application AU-2009/904481. Phase-contrast x-ray imaging provides images of high contrast and spatial resolution with temporal resolutions that allow multiple images to be acquired throughout the respiratory cycle. Thus, coupling x-ray phase contrast imaging with velocimetry can be used to measure lung tissue movement and determine velocity fields that define speed and direction of regional lung motion throughout a breath of a human or animal subject.
[0035] Movement of lung tissue shows the state of the lung tissue and enables regional measures. Air flow and breathing behaviours can be deduced from these measures. The parameter used for comparison may be any convenient parameter such as relative power, phase or amplitude at each forcing frequency. For example, it is possible to image lung motion of an input oscillation using phase contrast x-ray images of the lungs. Suitable measures extracted could include, for example (a) the frequencies of the oscillatory response of the lung tissued (response oscillation) oscillation, (b) phases of the response oscillations or (c) qualitative measures of strength of response oscillations at each frequency.
[0036] Regional maps of lung tissue motion reveal both the heterogeneity of normal lung motion, as well as any abnormal motion.
[0037] Other comparisons (and contrasts) may provide valuable information, such as comparisons of low frequency results against high frequency, or comparisons relating to phase, timing, regions, amplitudes.
[0038] This is typically carried out by the use of the Fourier Transform or other similar mathematical transformation.
[0039] In another aspect of embodiments described herein there is provided an apparatus for dynamic investigation of a subject lung using the method of the present invention, wherein the apparatus comprises:
a ventilator for delivering fluid pressure to the lung; a means for imparting an oscillation to the lung at one or more forcing frequencies so as to elicit a lung response a means of sensing the motion of the lung simultaneously with imparting of the oscillation to elicit a lung response; a means for measuring at least one parameter used in sensing and associated with the lung response at the forcing frequency in at least one region of the lung; processing means for comparing one of the sensing parameters at the forcing frequency with the response at the forcing frequency in at least one region of the lung; a means for recording the results of the comparison for at least one region of the lung.
[0046] Preferably the sensing parameter is a parameter used in imaging.
[0047] Clearly it is preferable for the method of the present invention to be carried out using a ventilator that can maintain stable and accurate pressure to the subject while the oscillation is delivered to the lung as well as being synchronised with imaging equipment and other devices such as data acquisition or medical equipment. However, many of the ventilators of the prior art cannot maintain sufficiently accurate pressure or timing. It is particularly preferable for the method of the present invention to be carried out using a ventilator that can provide high frequency ventilation (HFV) and/or provide the forced oscillation. HFV uses low tidal volumes at high rates to oscillate air into the subject and keeps the lung continuously inflated. Air mixing occurs by various mechanisms including direct bulk flow, Taylor dispersion, Pendelluft flow, cardiogenic mixing and molecular diffusion.
[0048] In a preferred embodiment, the ventilator for delivering fluid pressure to the lungs of a subject has a pump in operative connection with a first pressure vessel for control of the peak inspiratory pressure (PIP) of the subject wherein the volume of the first pressure vessel is substantially greater than the volume of the lungs of the subject. It is noted however that by using a sufficiently high flow rate pump and sufficiently fast acting valves and feedback system, increasingly smaller pressure vessels may be used.
[0049] The pressure in the ventilator may be controlled by any convenient means. For example, in one embodiment the pressure may be controlled through a sequence of measurements (via sensors) and adjustment of valves controlled through a computer interface and software. In another more preferred embodiment, the ventilator pressure may be controlled through a feedback sequence, which in turn is controlled locally by a microprocessor within the ventilator. The latter embodiment provides a much faster and more stable system.
[0050] In a further aspect, the ventilator for delivering fluid pressure to the subject lung has:
a pump in operative connection with a first pressure vessel for control of the peak inspiratory pressure (PIP) of the subject, and a housing for enclosure of the subject, the housing being in operative connection with the first pressure vessel.
[0053] In a particularly preferred embodiment the ventilator has at least two chambers, and is capable of performing HFV. In a yet further embodiment the ventilator has three chambers and is capable of performing HFV. In one embodiment, the ventilator vents to the atmosphere. In another embodiment the ventilator includes a second pressure vessel for control of the positive end expiratory pressure (PEEP).
[0054] In a yet further aspect, the ventilator for delivering fluid pressure to a subject has:
[0055] a pump in operative connection with a first pressure vessel for control of the peak inspiratory pressure (PIP) of the subject,
[0056] a second pressure vessel for control of the positive end expiratory pressure (PEEP) of the subject,
[0057] a housing for enclosure of the subject, the housing being in operative connection with the first pressure vessel and the second pressure vessel,
[0058] wherein the volumes of the first pressure vessel and the second pressure vessel are substantially greater than the volume of the lungs of the subject.
[0059] During ventilation of a subject, air flows from the first pressure vessel into the housing as the subject's lungs are inflated (inspiration); air flows from the housing into the second pressure vessel (expiration) and the subject's lungs are deflated.
[0060] In another aspect of embodiments described herein stable pressure is delivered to the lungs of a subject, the method of the present invention includes the steps of:
(1) enclosing the subject within a housing, the housing being in operative connection with a first pressure vessel held at a first (PIP) pressure and a second pressure vessel held at a second (PEEP) pressure, respectively, (2) admitting air from the first pressure vessel into the housing, then (3) admitting air from the housing into the second pressure vessel, and (4) repeating steps (2) and (3) multiple times.
[0065] If the inspiration time is sufficiently long, or the flow rate is sufficiently fast, the air may be admitted until the housing reaches a desired first pressure (in step 2) or a second pressure (in step 3).
[0066] Preferably the pressure within the vessels does not change by more than ±10%, preferably not more than ±5%, even more preferably not more than ±1%.
[0067] The pressure can be maintained through the use of a pressure vessel substantially larger than the inspired or expired volume. Typically the pressure vessels are each at least 10× the inspired or expired volume, more preferably at least 100× the inspired or expired volume.
[0068] Alternatively the pressure can be maintained by the feedback control system. As the feedback control system performance is increased, smaller pressure vessels will be required.
[0069] Other aspects and preferred forms are disclosed in the specification and/or defined in the appended claims, forming a part of the description of the invention.
[0070] In essence, embodiments of the present invention stem from the realization that conventional spirometry techniques such as FOT can be combined with lung imaging to provide information specific to every individual region across the image. Specifically they can be used to measure feature such as lung tissue movement and to determine velocity fields that define speed and direction of regional lung motion throughout a breath.
[0071] Advantages provided by the present invention comprise the following:
improved spatial and temporal resolution for assessing lung function and diagnosing lung conditions; improved assessment and diagnosis of the lung in a localised matter; accurate measures of regional lung function; improved dynamic lung function testing; improved identification of subtle changes of structure in (such as during the early stages of a disease or other disorder); synchronisation between ventilation and image acquisition to facilitate collection of data; and simultaneous lung function testing during ventilation
[0079] Further scope of applicability of embodiments of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure herein will become apparent to those skilled in the art from this detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0080] Further disclosure, objects, advantages and aspects of preferred and other embodiments of the present application may be better understood by those skilled in the relevant art by reference to the following description of embodiments taken in conjunction with the accompanying drawings, which are given by way of illustration only, and thus are not limitative of the disclosure herein, and in which:
[0081] FIG. 1( a ) is a plot of input pressure at the airway opening of a subject against time to illustrate input pressure oscillation. FIG. 1( b ) is a plot of the vector divergence against time to illustrate the measured vector divergence;
[0082] FIG. 2( a ) is a plot of frequency response of the pressure input from FIG. 1 , in the power spectrum to illustrate input pressure oscillation. FIG. 2( b ) is a plot of the frequency response of the measured vector divergence of FIG. 1 ;
[0083] FIG. 3 illustrates lung maps showing lung expansion at specific frequencies, the broken line indicating heart oscillation, the unbroken line indicating input oscillation;
[0084] FIG. 4( a ) and FIG. 4( b ) are plots of amplitude versus frequency of the measured response after Fourier transformation of the global average ( FIG. 4( a ) ) and the individual vectors ( FIG. 4( b ) ) to illustrate the horizontal ( 3 ) and vertical ( 1 ) velocity components;
[0085] FIG. 5 is an image of subject lungs generated using the method of the present invention using an amplitude of oscillation of 4 Hz with the subject lying on its side;
[0086] FIG. 6 is a plot of power versus frequency before (circles, 5 ) and after (squares, 7 ) the delivery of a dose of aerosol methacholine. There is a measurable decrease in the global average of expansion after the delivery of methacholine;
[0087] FIG. 7( a ) and FIG. 7( b ) correspond to FIG. 6 and are power maps of the 4 Hz oscillations before the delivery of methacholine ( FIG. 7( a ) ) and post delivery of methacholine ( FIG. 7( b ) );
[0088] FIG. 8( a ) is a schematic diagram of an imaging configuration according the present invention; FIGS. 8( b ) and 8( c ) illustrate the contrast for lung tissue obtained through phase-contrast x-ray imaging over absorption-based x-ray imaging. The various components included in the apparatus for imaging depicted in FIG. 8( a ) are as follows:
[0089] synchrotron storage ring, 9
[0090] bonding magnet, 11
[0091] monochromators, 13
[0092] x-ray beam, 15
[0093] sample, 17
[0094] scintillator, 19
[0095] optical lens, 21
[0096] optical mirror, 23
[0097] detector, 25 ; and
[0098] phase contrast image, 27 ;
[0099] FIG. 9( a ) shows the 3D nature of x-ray illumination and velocimetric cross-correlation analysis; FIG. 9( b ) shows in vivo detection of lung tissue motion. The various components depicted in FIG. 9( a ) are as follows;
[0100] X-ray beam, 29
[0101] lungs, 31
[0102] lung volume, 33
[0103] projection images at t 1 35 a , and t 2 , 35 b,
[0104] graph of velocity distribution, 37
[0105] cross-correlation, 39 ;
[0106] FIG. 10 shows the empirical relationship between lung divergence and tissue expansion; FIG. 10( a ) is a graph of integrated divergence (px) against lung volume (mL) where Int.Div=227.64× lung volume, and R2=0.98; and FIG. 10( b ) is a graph of lung volume (mL) against time measured using a plethysmograph (circles, 41 ) with normalised integrated divergence (crosses, 43 );
[0107] FIG. 11 shows physiological measures of lung pathology comparing controls with groups 36 hours after bleomycin exposure ( FIGS. 11( a ) & ( b )) and 6 days after exposure ( FIGS. 11( c ) & ( d ). In each graph the control result is depicted in black and the bleomycin result is depicted in white. In FIG. 11( b ) the bleomycin p<0.001. In FIG. 11( d ) the bleomycin p=0.02;
[0108] FIG. 12 shows velocimetric measures of lung pathology comparing controls with groups 36 hours ( FIG. 12( a ) and 6 days ( FIG. 12( b ) ) after bleomycin exposure. In each graph the control result is depicted by the black circles ( 47 ) and the bleomycin at p, 0.001 by the white circles ( 49 );
[0109] FIGS. 13( a ) and 13( b ) illustrate regional divergence with the lung and matching histology in FIGS. 13( c ), 13( d ) and 13( e ) ;
[0110] FIG. 14 is a schematic representation of the electrical wiring between components of one embodiment of a ventilator and data acquisition system suitable for use in the method and apparatus of the present invention, wherein black lines represent outputs and grey lines represent inputs from the data acquisition system. The components are as follows,
[0111] Personal computer, 51
[0112] Data acquisition box, 53
[0113] Peak inspiratory pressure (PIP) differential pressure transducer (DPT), 55
[0114] PIP valve, 57 (venting to atmosphere)
[0115] PIP vessel, 59
[0116] Positive end-expiratory pressure (PEEP) vessel, 61
[0117] Inspiration solenoid valve, 63
[0118] Expiration solenoid valve, 65
[0119] Inspiration valve, 67
[0120] Expiration valve, 69
[0121] PEEP DPT, 71
[0122] PEEP valve, 73 (venting to atmosphere)
[0123] Airway pressure DPT, 75 ;
[0124] FIG. 15 is a schematic representation of air flow through the ventilator of FIG. 14 , with arrows indicating the direction of flow which is generated by a gas pump ( 77 ) through a muffler ( 79 ) in relation to a subject lung ( 81 ).
DETAILED DESCRIPTION
[0125] Although many different imaging methods are suitable for use in the present invention, in a particularly preferred embodiment the present invention uses phase-contrast x-ray imaging (PCXI). PCXI exploits the phase change caused by x-ray refraction when passing between media of differing refractive indices to produce high contrast images of the lung. Interference between transmitted and refracted x-rays produces high contrast images of the air/tissue boundaries compared with conventional x-ray absorption techniques. It is able to achieve this because the phase shift of the x-rays is generally more than three orders of magnitude greater than the absorption over the diagnostic x-ray energy range (20 keV-90 keV). An important consequence of this is that phase-contrast images can be recorded with significantly lower dose than conventional images, which is particularly important for both longitudinal studies and dynamic studies where repeated imaging is required. These benefits are particularly relevant to scientific use. For clinical use, reduced radiation dose is of value for reduction in cancer risk.
[0126] Since lung tissue motion is complex, dynamic and heterogeneous, the present invention is a novel application of the mathematical concept of divergence. In particular, even when the imaging used is of a two-dimensional nature, the divergence measure is highly correlated to changes in lung volume.
[0127] FIG. 1( a ) illustrates a plot of input pressure perturbations as measured with a pressure sensor at the airway opening. The input signal is composed of 9 distinct and different frequencies. FIG. 1( b ) illustrates a plot of the vector divergence measured via a cross-correlation technique on phase contrast X-ray lung images. This is the global average of all locations across the lung (>1000 locations). Each vector location produces its own response to the input pressure wave, correlating to the specific local lung properties in the region.
[0128] FIG. 2( a ) illustrates frequency response of the pressure input from FIG. 1 , in the power spectrum. FIG. 2( b ) illustrates frequency response of the measured vector divergence of FIG. 1 . The 9 distinct frequencies can be obtained from the response of either pressure at the airway opening or the global average of vector divergence.
[0129] FIG. 3 illustrates lung maps showing lung expansion at specific frequencies. Both the heart and the pressure inputs contribute to lung expansion at different frequencies, the heart's first harmonic being at 3.6 Hz. The pressure wave input frequencies are 4, 6, 10 and 14 Hz. The heart harmonics can be seen and measured at 3.6, 7.2, 10.7 and 14.2 Hz. Above right is a larger version of the 4 Hz oscillation to highlight the distribution of power of oscillations at that specific frequency. In the contour maps the large amount of information obtained from this technique is shown as each vector location (>100 across the lung) provides its own complete measure of local lung health.
[0130] FIG. 4 illustrates the U and V velocity components measured as (a) an fft of the global average of lung expansion or (b) an fft of each vector then globally averaged. The first method more clearly highlights the difference between U and V velocity components that are created by the heart. This can be used to identify the frequencies at which the heart has an effect as well as their relative magnitudes, thus allowing for very accurate filtering of the heart.
[0131] FIG. 5 illustrates amplitude of oscillation at 4 Hz with the subject lying on its side. Note that the bottom lung is supporting the weight of the other lung and the heart above it, and as a result has less measured oscillation amplitude. It appears that the more inflated the lung, the greater the oscillation amplitude. This technique is thereby suitable to measure regional affects for not only lung health but also lung mechanics and posture related changes.
[0132] FIG. 6 illustrates the power of input oscillations before (blue) and after the delivery of a dose of aerosol methacholine (red). There is a measurable decrease in the global average of expansion after the delivery of methacholine. FIG. 7( a ) and FIG. 7( b ) illustrates corresponding power maps of 4 Hz oscillations before the delivery of methacholine ( FIG. 7( a ) ) and post delivery of methacholine ( FIG. 7( b ) ).
[0133] FIG. 8( a ) is a schematic diagram showing a suitable configuration for Phase-contrast x-ray imaging. FIGS. 8( b ) and 8( c ) are examples of the possible increase in contrast for lung tissue obtained through phase-contrast x-ray imaging over absorption-based x-ray imaging. PXCI exploits the phase change caused by x-ray refraction when passing between media of different refractive indices to produce high contrast images of the lung. Interference between transmitted and refracted x-rays produces high contrast images of the air/tissue boundaries compared with conventional x-ray absorption techniques as illustrated by the images shown at FIGS. 8( b ) and 8( c ) .
[0134] FIG. 9( a ) shows the 3D nature of x-ray illumination and velocimetric cross-correlation analysis. Each 2D sampling region in the projection images represents a 3D volume for which a distribution of velocities may be present. The preferred parameter for the present invention is the modal velocity, which may significantly differ from the mean. FIG. 9( b ) illustrates in vivo detection of lung tissue motion using instantaneous velocity of a healthy mouse lung ˜140 ms after the start of inspiration, shown as a vector field. Vectors are reduced in number (293 of 2640 displayed) for clarity. Vectors are coloured according to magnitude (from lowest; blue, to highest; red) of velocity. The complete time sequence of inspiration consists of 70 instantaneous vector fields (media), one of which is shown.
[0135] FIG. 10 shows the empirical relationship between lung divergence and tissue expansion. FIG. 10( a ) is a scatter-plot of divergence (integrated throughout entire data series) and lung volume (measured by water plethysmography) of a rabbit measured from its first breath. The solid line indicates a line of best fit, with an R 2 =0.98 indicating excellent correlation between the data sets. FIG. 10( b ) shows a time-series of lung volume (measured by water plethysmography) co-plotted with divergence (integrated throughout the entire data series and normalised by the co-efficient determined by the fit in FIG. 10( a ) .
[0136] FIG. 11 shows physiological measures of lung pathology comparing the compliance for treated groups with controls (statistically insignificant) at 36 hours ( FIG. 10( a ) ) and 6 days ( FIG. 10( c ) ) after treatment. Comparisons of the spontaneous tidal volumes (V T ) at 36 hours ( FIG. 10( b ) ) and 6 days after treatment ( FIG. 10( d ) ). Tidal volumes in controls are significantly lower than treated groups but are non-specific and global in nature.
[0137] FIG. 12 shows velocimetric measures of lung pathology comparing controls with groups 36 hours and 6 days after bleomycin exposure. Frequency distribution of the divergence (normalised to the average of controls) is compared for treated groups (n=4) with controls (n=3). Data are normalised by the average of the controls. As shown by FIG. 12( a ) , at 36 hours post treatment, treated mice have 24% greater divergence on average and 14% of treated lungs show difference 2× the control average compared with less than 5% for control lungs. As shown by FIG. 12( b ) , at 6 days post treatment, treated mice have 76% greater divergence on average and 47% of treated lungs show differences 2× the control average compared with less than 4% for control lungs.
[0138] FIG. 13 shows regional divergence within the lung and matching histology. FIGS. 13( a ) and 13( b ) are colour maps of regional divergence determined using x-ray velocimetry for typical (a) control, and (b) bleomycin-treated mice (6 days after exposure). Data are normalised by the average divergence across the control group and colour maps generated using the same colour scale (see legend). The mice treated with bleomycin (b) have dramatic regional alterations in the pattern of divergence. Histological image (c) from lung imaged in (a) is typical of the control group. Histological images ( FIGS. 13( d ) and 13( e ) ) from lung imaged in (b) are typical of the pathological group 6 days after bleomycin treatment. Treated lungs show both regions of healthy tissue (d) and localised regions that are both hypercellular and endatemous (e).
EXPERIMENTAL
[0139] The following non-limiting example illustrates how the combination of PCXI and velocimetry can produce quantitative measures of regional lung motion, which can be used to differentiate between normal and abnormal lung tissue. Furthermore the example illustrates that this technology is more sensitive and provides richer quantitative information for disease detection than other conventional measure such as global lung function tests and non-biased histological sampling.
[0140] Specifically, the present example illustrates the present invention when using single camera/2D imaging. Furthermore it illustrates the use of divergence as a measure of lung expansion. Despite the two-dimensional nature of imaging, the divergence measure is highly correlated to changes in lung volume. This measure was evaluated in a Bleomycin-induced lung injury model in immuno-deficient Balb/c nude mice that are known to have a reduced inflammatory response to bleomycin compared to other strains. Furthermore, mice are examined at 36 hours and 6 days after treatment to examine the early states of disease and determine whether disease progression can be detected.
Materials and Methods
[0141] Protocol: Adolescent Balb/c nude male mice were exposed to bleomycin (20 mg/kg in 20 uL saline; n=8; Sigma-Aldrich, Australia) or saline (20 uL; n=6) by intranasal instillation and lung function was tested daily using whole body plethysmography. Mice were imaged at 36 h (n=4) or 6 days (n=4) after treatment. For imaging, mice were anaesthetized (pentobarbital; 15 mg/kg i.p.), muscle relaxed (Pancuronium 1 mg/kg i.m.), intubated and placed in a prewarmed (37° C.) water-filled plethysmograph. During imaging, mice were ventilated using a custom-designed ventilator at a peak inspiratory pressure of 20 cmH 2 O and end expiratory pressure of 2 cmH 2 O. Inspiration and expiration times were 2.5 s and 1.5 s respectively. Although this is significantly less than the normal ventilation rate for free-breathing mice, the imaging procedures only lasted for 5 breaths (20 s) and was not expected to result in hypoxia or any changes in lung mechanics for these somnolent mice. Following imaging, mice were killed (Pentobarbital; 100 mg/kg i.p.) and the lungs fixed (in 10% formalin) via the airways at a distending pressure of 20 cmH 2 O. Paraffin-embedded sections (5 μm) were stained with Massons Trichrome and used for histological analysis. 5 fields of view were chosen at random from at least 3 randomly selected sections per mouse to measure the relative volume density of abnormal parenchymal lung regions. Then a subset analysis was performed to compare the relative tissue volume in normal and abnormal parenchymal regions using an unpaired T-test.
[0142] Phase-contrast X-ray imaging: Studies were conducted in experimental hutch 3 of BL20B2 at the Spring-8 synchrotron in Japan. The beamline consists of a bending magnet insertion device and Si-111 crystal monochromators, which generates a bright monochromatic X-ray beam. The X-ray beam transmits through the sample onto a scintillator, which converts the x-rays to visible light to be imaged by an optical detector system. Imaging was conducted at 25 keV with a sample-to-detector distance of 2 m. Images were acquired using an X-ray Converter (Hamamatsu, BM5) and an EMCCD (Hamamatsu, C9100-02) camera ( FIG. 8( a ) ) with an effective pixel size of 19.0 um. Image acquisition occurred at 29 frames per second (an exposure time of 20 ms with a 14.5 ms delay between exposures, corresponding to 34.5 ms between the start of frame acquisitions) and was synchronized with ventilation to acquire 70 frames during the first part of inspiration and 30 frames during the first part of expiration for each breath. The mice were imaged in the upright position with all images acquired to obtain a frontal view of the entire thorax without the need for scanning or tiling. In all images ( FIG. 9 ) the images are displayed without intensity inversion or laterally flipping and hence appear opposite in both regards in comparison to clinical x-ray images.
[0143] Velocimetry: The velocimetric analysis employed to measure lung motion is based on particle image velocimetry (PIV); this is an established technique for measuring differential fluid velocities, including blood flow. PIV determines the movement of particles from one image to the next, yielding information on both velocity and direction of particle movement. The basic concept is demonstrated in FIG. 9( a ) . Images are paired and discretised into small sub-regions and cross-correlations are performed between the sub-regions in consecutive images. The position of the maximum of the cross-correlation function determines the most common (modal) inter-frame displacement of the structures within each sub-region. Division of the displacement by the known inter-frame time yields the local modal velocity.
[0144] X-ray velocimetry has been utilised for the measurement of flow within channels for blood flow and has recently been adapted to 3D analysis. The high contrast intensity patterns produced by PCXI of the lung can be used instead of having to introduce exogenous particles as is the practice in conventional PIV. As a result, a comprehensive map displaying regional tissue velocities can be generated at all stages of the breathing cycle.
[0145] Whole animal motion was removed from image sequences by velocimetric analysis of upper vertebrae, followed by interpolation of images onto a static reference frame. Lungs were isolated from images by band-pass filtering using the appropriate image frequencies and regions containing the lungs were identified and masked. Following this pre-processing, velocimetric analysis was conducted for 5 consecutive inspirations using customised software and the date phase-average to produce data sets of 70 frames displaying the velocity vector fields throughout inspiration for each animal.
[0146] Divergence: At every time-point the spatial derivatives of the velocity fields can be evaluated and summed to form the two-dimensional divergence field. The spatial derivative distinguishes between bulk displacement of tissue and regional variations in tissue displacement, highlighting local differences in motion between regions. The local differences are directly related to local tissue expansion, and hence local variations in the divergence would be considered to be a measure of heterogeneity of tissue expansion and, by implication, tissue properties. For the sake of clarity of expression this projected divergence in motion will hereafter simply be referred to as the divergence. The total divergence over inspiration is the sum of the divergence between each pair of subsequent time points. As the data are integrated over the entire inspiration, total divergence is represented in a single map.
[0147] Statistics: Unpaired one-tailed t-tests were used to compare mean tidal volume and histological parameters. Two-way repeated measures ANOVA was used to determine differences in frequency distributions of divergence and time of divergence. Results were considered statistically significant at p<0.05. Values are reported as mean+/−SEM (unless stated otherwise).
Results
[0148] Physiological analysis: Plethysmography was used to measure tidal volume (VT) during both spontaneous breathing and mechanical ventilation. Lung compliance was assessed only during mechanical ventilation, as airway pressure measurements were not available during spontaneous breathing. At 36 h after bleomycin treatment, the spontaneous VT was significantly increased from 1.4+/−0.1 mL/kg in saline-treated mice to 1.9+/−0.1 mL/kg in bleomycin-treated mice, whereas spontaneous breathing rates were reduced from 480+/−38 to 283+/−34 breaths/min. However, no significant differences in global lung compliance (0.68+/−0.04 vs 0.71+/−0.10 mL/cmH 2 O/kg) could be detected during mechanical ventilation ( FIG. 11 ). Similarly, at 6 days after bleomycin treatment, the spontaneous VT remained significantly elevated (1.2+/−0.1 vs 1.6+/−0.2 mL/kg) and the ventilation rate was reduced (440+/−13 vs 235+/−40 breaths/min), but no significant affect on global lung compliance (0.5+/−0.04 vs 0.55+/−0.05 mL/cmH 2 O/kg) was detected during mechanical ventilation ( FIGS. 11( c ) & 11 ( d )).
[0149] Velocimetry: Determined using x-ray velocimetry, the velocity vectors define the timing and extent of regional lung motion throughout a breath. The vectors measured at mid-inspiration demonstrate that regional lung motion is very heterogeneous ( FIG. 9 ) at this point in the breathing cycle.
[0150] Divergence-validation: To validate the divergence analysis, an existing, published, PCXI image data set was evaluated using the divergence analysis outlined herein. PCXI image were acquired as rabbit foetus lungs were slowly ventilated from their first breaths (in situ) inside a water plethysmograph—allowing concurrent measurements of lung air volume as it rises from zero.
[0151] The PCXI images were analysed for velocimetry and divergence. The divergence data was then integrated throughout the entire series rather than just each breath and compared to the plethysmograph data. A scatter-plot of the integrated divergence ( FIG. 10( a ) ) plotted against the lung volume as measured by water plethysmograph shows strong correlation between the two quantities (R 2 =0.98). The gradient of the line of best-fit could be considered as a combination of the image magnification (pixel size) and an equivalent thickness of the lung since this gradient represents the empirically-determined conversion vector to convert between the change in area (in pixels) and a change in volume (mL). To demonstrate the direct relationship between these quantities, the divergence data has been normalised by the empirical thickness and plotted ( FIG. 10( b ) ) with the lung volume as measured by water plethysmography against time. Despite some minor inaccuracies brought about by the imperfect sealing of the animal in the water plethysomgraph and the two-dimensional nature of the image data, the excellent agreement between these data demonstrates the direct link between divergence and tissue expansion and hence tissue mechanical properties.
[0152] Divergence-bleomycin treatment: Divergence data for bleomycin treated mice and controls were normalised by the average of controls and accumulated into frequency distribution curves, demonstrating that major difference (p<0.001) in regional lung motion can be detected between saline-treated and bleomycin-treated mice both 36 h and 6 days after treatment. Frequency distribution curves ( FIG. 12 ) show that divergence, within individual regions of lung tissue, was on average 24% greater in bleomycin-treated mice compared to saline-treated controls at 36 h after treatment, despite having the same global VT. Moreover, in bleomycin treated mice at 36 h after treatment, 14% of lung regions showed local differences twice the mean value in saline-treated controls; less than 5% of lung regions showed this degree of divergence in control mice, indicating a three-fold increase between bleomycin-treated and control mice.
[0153] At 6 days after bleomycin treatment, the changes in lung motion were more enhanced than those detected at 36 h after treatment. Indeed, despite no changes in global lung compliance, x-ray velocimetry detected a highly significant shift in the frequency distribution curve towards greater divergence ( FIG. 12( b ) ). On average, the divergence of individual lung regions was 76% greater in bleomycin-treated mice compared to saline-treated controls. Furthermore 47% of lung regions in treated mice show local differences in motion twice the mean value of saline-treated mice, while less than 4% of lung regions showed this degree of divergence in saline-treated mice. Hence there is nearly a 12 fold difference in divergence between bleomycin-treated mice and controls at 6 days after treatment. From these data, regional maps of divergence can be reconstructed and superimposed on the lung image to identify regions with abnormal motion ( FIG. 13 ).
DISCUSSION
[0154] Although ventilators, plethysmographs and spirometers can measure many characteristics of lung function, those measures reflect the integrated average of the entire lung. As a result these techniques have limited ability to detect regional lung disease until it is sufficiently widespread to influence total lung function. In contrast, the present invention uses the capabilities of x-ray velocimetry to non-invasively detect breath-by-breath alterations in regional lung motion that occur even during the early stages of lung disease. Importantly, the velocimetric technique offers the advantages of detecting regional changes in lung function early, accurately and most importantly, in situ.
[0155] Superposition of the lung tissue velocity maps over the phase-contrast images acquire at mid-inspiration (140 ms after inspiration onset) clearly demonstrates the heterogeneity of lung motion ( FIG. 9 ). Combining consecutive images reveals the changing dynamic of the velocity vector field during a breath and demonstrates that regional lung tissue motion is complex and non-linear. Indeed, regional velocities are most likely influenced by local characteristics of regional compliance, the compliance and motion of nearby tissue as well as the proximity to structure such as the diaphragm, heart and chest wall. For example, lung tissue near the diaphragm displayed significantly more motion than tissue near the apex of the lung ( FIG. 9( b ) ) which is likely due to differences in compliance as well as motion and activity of the chest wall that is immediately adjacent to the lung tissue. To accommodate the large differential in normal motion across the lung, a functional measure was derived from the velocity fields to identify regions with abnormal motion potentially caused by disease. Specifically the local divergence was calculated, normalised to the average for all controls of reach treatment period (eg 36 hours or 6 days) so that differences could be detected.
[0156] The measure of divergence was derived from integration of the velocity vector field within each region over an entire breath. It is well understood that the divergence of a velocity field relates to the local expansion or contraction of the object, which in this case is lung tissue. As such the divergence accounts for normal variations in tissue motion (such as the increased motion near to the diaphragm compared to the apex) and converts heterogeneous patterns of tissue motion (displayed by normal tissue) to a homogenous pattern of divergence. However it is anticipated that heterogeneous regions of tissue properties (either resistance or compliance) will result in local variations in divergence.
[0157] However, lung tissue motion is three-dimensional and divergence measures are two-dimensional. Therefore the most correct interpretation of the measure of divergence is that it directly relates to local heterogeneity of lung tissue motion cause by differences in expansion. If all ventilation parameters, such as inflation times, pressures and gas flows are kept constant, their local heterogeneity in motion reflects differences in the mechanical response of lung tissue across the lung. This altered response must be due to either changes in the tissue mechanical properties, or a constriction/dilation of the airways leading to local alteration in resistance or compliance.
[0158] To test the ability of x-ray velocimetry and our subsequent analysis to detect abnormal lung motion, mice were exposed to bleomycin which resulted in progressive lung injury. Inhaled bleomycin is well characterised and commonly used experimental model of pulmonary fibrosis that begins with the initiation of an inflammatory cascade. Since Balb/c nude mice (an immuno-deficient strain) were utilised, it is not surprising that the pulmonary fibrotic response was reduced in these mice compared with reports in other strains. This is likely because inflammatory responses are reduced in these mice, although a recent study has also observed a similar reduced response in conventional Balb/c mice. In any event it is apparent that the induced pathological changes were insufficient to affect global lung compliance at the time points measured, as observed previously in conventional Balb/c mice. The mice were deliberately examined at 36 hours and 6 days after treatment which encompasses the early stages of disease pathogenesis when the induced changes can be detected histologically but not physiologically. Indeed a previous study has indicated that the maximum response to bleomycin occurs at 21 days for conventional Balb/c mice which is the only time that functional changes can be detected. However, it is clear from the histological analysis ( FIG. 13 ) that the bleomycin treatment was sufficient to cause observable focal lesions within lung tissue.
[0159] The present velocimetric analysis in bleomycin-treated mice revealed highly significant changes in regional lung motion compared to saline-treated mice. Despite having similar tidal volumes and inflation pressures during mechanical ventilation (indicating no change in global compliance), bleomycin treatment increased divergence across the lung by 24% at 36 h and by 76% at 6 days. This highly sensitive measure yielded a three fold difference between the groups after only 36 hours of treatment and was increased further after 6 days of treatment.
[0160] It is apparent that it was not possible to detect a change in global lung compliance during mechanical ventilation at either 36 hours or 6 days after treatment, but that tidal volumes during spontaneous breathing were significantly increased by bleomycin treatment at both times ( FIG. 11 ). The higher tidal volumes during spontaneous breathing were partially matched with lower ventilation rates resulting in minute ventilation (mL/min/kg) values that were slightly reduce by statistically similar in bleomycin and saline-treated mice.
[0161] In summary PCXI combined with velocimetry can measure regional lung motion and define the regional velocity changes at each stage of the respiratory cycle. Despite the large heterogeneity in normal motion across the lung, a detailed analysis of the velocity vectors can provide a very sensitive method for detecting abnormal motion caused by respiratory disease.
Ventilator
[0162] A time-cycled pressure-limited ventilator was developed, the ventilator operating using LabVIEW's Virtual Instrument (VI) controls to synchronise image acquisition with mechanical ventilation of small animals. A personal computer (PC) along with a data acquisition module (NI USB-6259) and National Instruments Lab VIEW software were used to control the ventilator, as illustrated in FIG. 14 . Table 1 provides a detailed description of the ventilator components. The data acquisition system connects to the PC with a Universal Serial Bus (USB) cable and can handle up to 4 analog outputs, 80 analog inputs and 48 digital input/output channels at 1.25 MS/s. LabVIEW can simultaneously control multiple devices and readily interface with external hardware since many hardware drivers are included in the programming library. The main advantage of the virtual interface is that all parameters (eg air pressure and flow rate) can be controlled remotely with real-time display.
[0000]
TABLE 1
Component
Function
Specification
Data acquisition system (NI
To synchronise the PC with
4 analog outputs, 80 analog
USB-6259)
the ventilator components
inputs (16-bit), 48 digital I/O,
1.25 MS/s
LabVIEW software
To record outputs from and
Version 8.5
send inputs to the data
acquisition system
Pump
To provide a continuous flow
of air
Muffler
To dampen the pulsatile flow
250 cm 3
from the pump
Pressure vessels (PIP and
To supply air of a fixed
Volume = approx. 100x larger
PEEP)
pressure to the lung during
than total volume of lung and
inspiration and expiration
tubing
Solenoid valve (Cole-
To open and close during
Response time: 15 ms
Parmer, EW-01367-50)
inspiration and expiration
Max flow rate: 16 LPM
Stepping motor valves,
To maintain the pressure
Speed: 0-5 V DC Maximum flow
Aalborg, SMV40-S
inside the PIP and PEEP
rates: 1000 sL/min
vessels and air flow to
Direction: TTL logic
the lung
LED indicators
Differential pressure
To measure pressure within
LED range indication
transducer (DPT), Ashcroft
PIP and PEEP vessels and
Differential pressure ranges: 3-
DXLdp
the lung
127 cm(H 2 O)
[0163] FIG. 15 depicts the manner in which air was cycled around the ventilator and delivered to the lung. Two pressure vessels, set at different pressures were used to control the PIP and PEEP. At the start of inspiration the inspiratory solenoid valve opened whilst the expiratory solenoid remained closed ( FIGS. 14 and 15 ) for the entire set inspiratory time. Air from the PIP vessel flowed to the lung through the inspiratory solenoid via a variable restrictor valve; this allowed the air to flow into the lungs until the airway pressure reached the pressure of the PIP vessel. As the PIP and PEEP vessels were of sufficiently large volume (˜1 L/box), the volume change associated with opening and closing of the respiratory solenoids did not significantly influence the pressure within the vessels. This provided a high degree of stability with the applied PIP and PEEP pressures. A variable restrictor valve allowed almost infinite variability of the rate of gas flow into the lung from the pressure vessel, which in turn was controlled remotely via the virtual interface. As a result the inspiratory pressure wave form could be varied and the length of an inspiratory pressure plateau (as a proportion of inspiration time) could be set by regulating the inspiratory airflow independently of this PIP. Upon expiration the states of the respiratory solenoids are simultaneously flipped, allowing the lungs to deflate to the lower PEEP level for a preset period. During expiration, airflow from the lung into the PEEP box could also be regulated via a restrictor valve, as shown in FIG. 15 . Both the inspiratory and expiratory times can be updated in software while the ventilator is operating. As a safety precaution the solenoids simultaneously closed when the ventilation sequence was terminated to prevent over-distension of the airways.
[0164] A ventilator of this type is capable of performing high frequency ventilation up to at least 33 Hz, which is well in excess of typical clinical usage of about 2 to 12 Hz.
[0165] While this invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modification(s). This application is intended to cover any variations uses or adaptations of the invention following in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth.
[0166] As the present invention may be embodied in several forms without departing from the spirit of the essential characteristics of the invention, it should be understood that the above described embodiments are not to limit the present invention unless otherwise specified, but rather should be construed broadly within the spirit and scope of the invention as defined in the appended claims. The described embodiments are to be considered in all respects as illustrative only and not restrictive.
[0167] Various modifications and equivalent arrangements are intended to be included within the spirit and scope of the invention and appended claims. Therefore, the specific embodiments are to be understood to be illustrative of the many ways in which the principles of the present invention may be practiced. In the following claims, means-plus-function clauses are intended to cover structures as performing the defined function and not only structural equivalents, but also equivalent structures. For example, although a nail and a screw may not be structural equivalents in that a nail employs a cylindrical surface to secure wooden parts together, whereas a screw employs a helical surface to secure wooden parts together, in the environment of fastening wooden parts, a nail and a screw are equivalent structures.
[0168] It should also be noted that where a flowchart is used herein to demonstrate various aspects of the invention, it should not be construed to limit the present invention to any particular logic flow or logic implementation. The described logic may be partitioned into different logic blocks (e.g., programs, modules, functions, or subroutines) without changing the overall results or otherwise departing from the true scope of the invention. Often, logic elements may be added, modified, omitted, performed in a different order, or implemented using different logic constructs (e.g., logic gates, looping primitives, conditional logic, and other logic constructs) without changing the overall results or otherwise departing from the true scope of the invention.
[0169] Various embodiments of the invention may be embodied in many different forms, including computer program logic for use with a processor (e.g., a microprocessor, microcontroller, digital signal processor, or general purpose computer and for that matter, any commercial processor may be used to implement the embodiments of the invention either as a single processor, serial or parallel set of processors in the system and, as such, examples of commercial processors include, but are not limited to Merced™, Pentium™, Pentium II™, Xeon™, Celeron™, Pentium Pro™, Efficeon™, Athlon™, AMD™ and the like), programmable logic for use with a programmable logic device (e.g., a Field Programmable Gate Array (FPGA) or other PLD), discrete components, integrated circuitry (e.g., an Application Specific Integrated Circuit (ASIC)), or any other means including any combination thereof. In an exemplary embodiment of the present invention, predominantly all of the communication between users and the server is implemented as a set of computer program instructions that is converted into a computer executable form, stored as such in a computer readable medium, and executed by a microprocessor under the control of an operating system.
[0170] Computer program logic implementing all or part of the functionality where described herein may be embodied in various forms, including a source code form, a computer executable form, and various intermediate forms (e.g., forms generated by an assembler, compiler, linker, or locator). Source code may include a series of computer program instructions implemented in any of various programming languages (e.g., an object code, an assembly language, or a high-level language such as Fortran, C, C++, JAVA, or HTML. Moreover, there are hundreds of available computer languages that may be used to implement embodiments of the invention, among the more common being Ada; Algol; APL; awk; Basic; C; C++; Conol; Delphi; Eiffel; Euphoria; Forth; Fortran; HTML; Icon; Java; Javascript; Lisp; Logo; Mathematica; MatLab; Miranda; Modula-2; Oberon; Pascal; Perl; PL/I; Prolog; Python; Rexx; SAS; Scheme; sed; Simula; Smalltalk; Snobol; SQL; Visual Basic; Visual C++; Linux and XML.) for use with various operating systems or operating environments. The source code may define and use various data structures and communication messages. The source code may be in a computer executable form (e.g., via an interpreter), or the source code may be converted (e.g., via a translator, assembler, or compiler) into a computer executable form.
[0171] The computer program may be fixed in any form (e.g., source code form, computer executable form, or an intermediate form) either permanently or transitorily in a tangible storage medium, such as a semiconductor memory device (e.g, a RAM, ROM, PROM, EEPROM, or Flash-Programmable RAM), a magnetic memory device (e.g., a diskette or fixed disk), an optical memory device (e.g., a CD-ROM or DVD-ROM), a PC card (e.g., PCMCIA card), or other memory device. The computer program may be fixed in any form in a signal that is transmittable to a computer using any of various communication technologies, including, but in no way limited to, analog technologies, digital technologies, optical technologies, wireless technologies (e.g., Bluetooth), networking technologies, and inter-networking technologies. The computer program may be distributed in any form as a removable storage medium with accompanying printed or electronic documentation (e.g., shrink wrapped software), preloaded with a computer system (e.g., on system ROM or fixed disk), or distributed from a server or electronic bulletin board over the communication system (e.g., the Internet or World Wide Web).
[0172] Hardware logic (including programmable logic for use with a programmable logic device) implementing all or part of the functionality where described herein may be designed using traditional manual methods, or may be designed, captured, simulated, or documented electronically using various tools, such as Computer Aided Design (CAD), a hardware description language (e.g., VHDL or AHDL), or a PLD programming language (e.g., PALASM, ABEL, or CUPL). Hardware logic may also be incorporated into display screens for implementing embodiments of the invention and which may be segmented display screens, analogue display screens, digital display screens, CRTs, LED screens, Plasma screens, liquid crystal diode screen, and the like.
[0173] Programmable logic may be fixed either permanently or transitorily in a tangible storage medium, such as a semiconductor memory device (e.g., a RAM, ROM, PROM, EEPROM, or Flash-Programmable RAM), a magnetic memory device (e.g., a diskette or fixed disk), an optical memory device (e.g., a CD-ROM or DVD-ROM), or other memory device. The programmable logic may be fixed in a signal that is transmittable to a computer using any of various communication technologies, including, but in no way limited to, analog technologies, digital technologies, optical technologies, wireless technologies (e.g., Bluetooth), networking technologies, and internetworking technologies. The programmable logic may be distributed as a removable storage medium with accompanying printed or electronic documentation (e.g., shrink wrapped software), preloaded with a computer system (e.g., on system ROM or fixed disk), or distributed from a server or electronic bulletin board over the communication system (e.g., the Internet or World Wide Web).
[0174] “Comprises/comprising” and “includes/including” when used in this specification is taken to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof. Thus, unless the context clearly requires otherwise, throughout the description and the claims, the words ‘comprise’, ‘comprising’, ‘includes’, ‘including’ and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.
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A method for dynamic investigation of a subject lung, the method comprising the steps of: (i) imparting an oscillation to the lung at one or more forcing frequencies so as to elicit a lung response, (ii) sensing the response of the lung simultaneously with the imparting of the oscillation to elicit a lung response, (iii) choosing at least one parameter used in the sensing to define the lung motion associated with the lung response, (iv) comparing one of the chosen parameters at each forcing frequency with the response at the forcing frequency in at least one region of the lung, and (v) recording the comparison of step (iv).
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FIELD OF THE INVENTION
[0001] The present invention relates to medical devices for monitoring analytes in a living body, such as monitoring glucose levels in people with diabetes. More particularly, the invention relates to providing meter users with test reminder capabilities.
BACKGROUND OF THE INVENTION
[0002] In recent years, people with diabetes have typically measured their blood glucose level by lancing a finger tip or other body location to draw blood, applying the blood to a disposable test strip in a hand-held meter and allowing the meter and strip to perform an electrochemical test of the blood to determine the current glucose concentration. Such discrete or individual, in vitro tests are typically conducted at least several times per day. Detailed descriptions of such glucose monitoring systems and their use are provided in U.S. Pat. No. 7,058,437, issued to TheraSense, Inc. on Jun. 6, 2006, which is incorporated by reference herein in its entirety.
[0003] In vivo glucose monitoring devices are currently being developed to provide continuous glucose monitoring. Some of these continuous systems employ a disposable, transcutaneous sensor that is inserted into the skin to measure glucose concentrations in interstitial fluid. A portion of the sensor protrudes from the skin and is coupled with a durable controller and transmitter unit that is attached to the skin with adhesive. A wireless handheld unit is used in combination with the skin-mounted transmitter and sensor to receive glucose readings periodically, such as once a minute. At a predetermined time interval, such as every three, five or seven days, the disposable sensor is removed and replaced with a fresh sensor which is again coupled to the reusable controller and transmitter unit. With this arrangement, a person with diabetes may continuously monitor their glucose level with the handheld unit. The handheld unit of the in vivo system can also include an in vitro test strip meter for conducting individual tests as described above. The in vitro test strip meter can be used to calibrate the continuous monitoring system each time a new in vivo sensor is implanted. Additionally, the in vitro test strip meter can be used as back up in case the in vivo system fails, a new sensor is equilibrating, or when the transmitter must be turned off, such as during takeoffs and landings when aboard an airliner. Detailed descriptions of such a continuous glucose monitoring system and its use are provided in U.S. Pat. No. 6,175,752, issued to TheraSense, Inc. on Jan. 16, 2001, which is incorporated by reference herein in its entirety.
[0004] The purpose of in vitro or in vivo glucose monitoring is to assist people with diabetes to keep their blood glucose within a predetermined range. If a person's blood glucose level rises too high, hyperglycemia can occur. The short term effects of hyperglycemia can include fatigue, loss of cognitive ability, mood swings, excessive urination, excessive thirst and excessive hunger. Of more immediate concern, if a person's blood glucose level drops too low, hypoglycemia can occur. Like hyperglycemia, symptoms of hypoglycemia also include fatigue and loss of cognitive ability. If unchecked, however, hypoglycemia can quickly lead to loss of consciousness or coma. Some diabetics have little or no symptoms of hypoglycemia, or find it difficult to distinguish between symptoms of hyperglycemia and hypoglycemia. Long term effects of not keeping blood glucose levels within a proper range include health complications such as cardiovascular disease, chronic renal failure, retinal damage which can lead to blindness, nerve damage, impotence, and gangrene with risk of amputation of toes, feet, and even legs. Clearly, proper glucose monitoring and corrective action based on the monitoring is essential for people with diabetes to maintain their health.
[0005] An ideal blood glucose range can vary from person to person. However, a fairly typical goal for someone with diabetes can be 75 to 175 milligrams of glucose per deciliter of blood (i.e. 75 to 175 mg/dL). Eating causes blood glucose concentrations to go up, while administration of insulin and exercise both cause glucose to go down. Different types of food affect how much and how fast glucose will rise. Stress, fatigue and other factors can also have a significant affect on glucose levels. In light of the many factors that affect blood glucose, a diabetic person must monitor glucose at least several times a day to maintain a proper balance. Moreover, it is often not enough to take a single test to determine a current glucose level. A second test sufficiently spaced apart in time from the first (e.g. 15 or 30 minutes) may be advisably to determine not just the current glucose level, but whether the level is rising, falling or remaining level.
SUMMARY OF THE INVENTION
[0006] According to aspects of some embodiments of the present invention, an in vitro analyte monitoring system is provided with alert features. These alert features assist a user in maintaining proper analyte levels. Blood glucose is one of many analytes that may be maintained using aspects of the present invention. For each user, an ideal or target analyte range can be established. Above and below this ideal range, upper and lower ranges of moderate concerns, respectively, can also be established. Above the upper range of moderate concern, an upper range of high concern can be established. Similarly, below the lower range of moderate concern, a lower range of high concern can also be established. By way of example, a user can make in vitro blood glucose measurements, such as with a handheld meter and test strip. In some embodiments of the invention, the user can be alerted by the test meter when a measurement falls within either of the upper or lower ranges of moderate concern. Preferably, the alert indicates to the user which of the upper and lower ranges of moderate concern the measurement falls into.
[0007] According to other aspects of the invention, an in vitro analyte monitoring system is provided with alarm features. These alarm features also assist a user in maintaining a proper analyte (e.g., glucose) level. As described above, upper and lower analyte ranges of high concern can be established. In some embodiments of the invention, a test meter can be provided with alarms that warn the user when a measurement falls within either of the upper or lower ranges of high concern. Preferably, the alarm indicates to the user which of the upper and lower ranges of high concern the measurement falls into. Additionally, it is preferable that the alarms indicate a higher level of urgency than do the previously described alerts. Note that a user's analyte level may pass from an ideal range, through a range of moderate concern and into a range of high concern before the user conducts an analyte measurement. In such cases, the user may be provided with an alarm without receiving an alert first.
[0008] According to other aspects of the invention, an analyte monitoring system is provided with reminder features. The reminder features also assist a user in maintaining a proper analyte (e.g., glucose) level. Analyte ranges of moderate or high concern can be established, as described above. In some embodiments of the invention, a test meter can have a reminder feature that is triggered when a measurement value falls into a range of moderate or high concern. The reminder can prompt the user after a predetermined period of time to take another analyte measurement to ensure that the analyte level is heading toward or has returned to the ideal range. Such a reminder feature can be particularly helpful since it frees the user from either trying to remember when to retest or from setting an external alarm, if available. For those users that require supervision, such as children, the reminder feature automatically assists the care giver by providing the user with a retest reminder, even when the care giver is not present to perform the task of reminding.
[0009] According to various aspects of the invention, the above-described alerts, alarms and reminders can be conveyed to the user visually, such as with a graphical user interface (GUI) or light emitting diode(s) (LED). In one embodiment of the invention, a fixed-segment liquid crystal display (LCD) is used as the GUT, with the value of the analyte measurement appearing in flashing numerals when not in the ideal range. In addition, or in an alternative embodiment, up and down arrow icons can be provided to display when an analyte measurement is in the upper or lower range of moderate and/or high concern. For example, a solid arrow icon can be displayed when the level is in the range of moderate concern, and a flashing arrow can be displayed when the level is in the range of high concern. Different icons can be used depending on whether the level is in the range of moderate or high concern. For instance, an arrow icon having a first size can be displayed when the analyte level is in the range of moderate concern, and a larger or vertically displaced arrow icon can be displayed when the level is in the range of high concern. Alternatively, a horizontal arrow can be displayed when the analyte level is in the ideal range, an arrow inclined upward or downward can be displayed when the level is in the upper or lower range of moderate concern, respectively, and an arrow inclined at a steeper upward or downward angle can be displayed when the level is in the upper or lower range of high concern, respectively. Alternatively, the opposite directions of the above arrows can be used to be indicative the course of action to be taken rather than whether the current level is high or low. For instance, a high analyte level may display a downward pointed arrow to indicate that the user should lower his or her analyte level. In other embodiments, symbols such as +, − and = can be used to indicate high, low and on track readings, respectively. The use of a dot matrix display instead of or in combination with a fixed element display may be employed, e.g., to allow for more flexibility in providing alerts and/or alarms and/or reminders to a user. Text may be shown on the display, with or without accompanying icons, and with or without user feedback, to provide information to the user about a particular alert, alarm and/or reminder. For example, after a test result falling into a range of concern, text may appear explaining the significance of the results, proposing one or more courses of action, and/or indicating that the user should re-test after a certain period of time. After such a period of time has elapsed, a further text message may appear which may include instructions to conduct further tests. Some text messages may be downloaded or otherwise activated as part of a prescription from a Health Care Provider.
[0010] To reduce size and/or cost of a meter, one or more LEDs may be used to convey an alert, alarm or reminder to a user. For instance, a single LED can be illuminated when the analyte measurement is not in the ideal range. The LED can be solid when in the range of moderate concern, and flashing when in the range of high concern. Different colors in one or more LEDs can indicate different ranges. For instance green can indicate the analyte level is in the ideal range, yellow can indicate the level is in a range of moderate concern and red can indicate the level is in a range of high concern. Two LEDs can be used to indicate whether the value is high or low (or whether the user's analyte level should be raised or lowered). Three LEDs can be used, for instance with a first LED indicating an analyte level below the ideal range, a second LED indicating a level in the ideal range, and a third LED indicating a level above the ideal range. Four LEDs can be used to indicate an analyte level in the lower range of high concern, the lower range of moderate concern, the upper range of moderate concern and the upper range of high concern, respectively. A fifth LED can be added to indicate a level in the ideal range.
[0011] In addition to or instead of visual indicators of alerts, alarms and reminders, a glucometer constructed according to aspects of the present invention can incorporate audible or physical feedback. Since diabetes can adversely affect a person's eyesight, such forms of user interface can become necessary. In one embodiment of the invention, a meter can emit an audible tone to indicate an analyte reading that is outside of the ideal range. A high tone can be used to indicate a reading that is above the ideal range while a low tone can be used to indicate a reading that is below. A pulsing or intermittent tone can be used to indicate a reading that is in a range of high concern. A varying number of pulses and other variations can be employed to indicate what range the analyte reading is in. Similarly, a vibratory signal, such as used in cell phones, can be used with different variations for indicating alerts, alarms and reminders to a user.
[0012] According to various aspects of the invention, the above-described alerts, alarms and reminders can be set with default parameters during manufacture, and/or may he settable by a HCP (Health Care Professional such as a Doctor or Certified Diabetes Educator) with levels corresponding to prescribed values for a user, and/or may be user configurable. In one embodiment of the invention, a meter is provided that is set to automatically remind the user to retest after a predetermined period of time, which may be preset or configured, after a test that falls outside of an ideal analyte range. The meter may be configured to allow the user or healthcare professional to disable this feature. In an alternative embodiment, the meter is provided “out of the box” with such a reminder feature disabled, but with provisions to allow the user or healthcare professional to enable it and/or set configuration parameters. A meter can be provided that allows different reminder parameters depending on whether the underlying analyte measurement is in a range of moderate concern or a range of high concern. In one embodiment, the glucometer reminds the user with a first audible signal to retest a first time period (e.g. 30 minutes) after a test result falling in a range of moderate concern, and reminds the user with a second audible signal to retest after a second time period (e.g. 15 minutes) after a test result falling in a range of high concern. In certain embodiments, the second audible signal has a higher volume level and/or longer duration than the first audible signal, and the second time period may be shorter than the first time period. In this embodiment, the second audible signal can also be accompanied with a vibratory signal. In this or alternative embodiments, the first and/or second signals can continue or repeat if not acknowledged by the user, such as with the push of a button, or with an actual test being conducted. The parameters of the reminders can also be different based on whether the analyte reading is above or below the ideal range, and/or can vary depending on the actual value of the analyte measurement. For each reminder (alert or alarm) the settings may include, but are not limited to, the analyte value, time to reminder, type of reminder (e.g. visual, audible, vibratory, or a combination thereof), persistence of the reminder (e.g. once, once a minute for n times, or once a minute until acknowledged), and the number of times (n) a persistent reminder will repeat.
[0013] According to other aspects of the present invention, a glucometer can be provided with alert and/or alarm and/or reminder settings that can be configured and locked until an access code is supplied, such as by a HCP or a caregiver. Such an arrangement prevents those under the care of a HCP from changing a prescription or those receiving guidance from a caregiver, for instance children, from modifying configuration values. This prevents inadvertent changes to the configuration values. It also prevents the bypassing of alerts, alarms or reminders, such as when a user wants to engage in behavior that may affect analyte levels, e.g., eat improperly. According to other aspects, configuration settings may be set through a glucometer data port, such as when the glucometer is connected to a computer for the uploading and/or downloading of information. In certain embodiments, a HCP or a caregiver is allowed to set and lock configuration values through the data port. Though the configuration locking concepts are described for a discrete in vitro measurement system (e.g. a glucometer), they are also applicable for continuous in vivo monitoring systems as described above.
[0014] Various analytes may be monitored using aspects of the present invention. These analytes may include but are not limited to lactate, acetyl choline, amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase (e.g., CK-MB), creatine, DNA, fructosamine, glucose, glutamine, growth hormones, hematocrit, hemoglobin (e.g. HbAlc), hormones, ketones, lactate, oxygen, peroxide, prostate-specific antigen, prothrombin, RNA, thyroid stimulating hormone, and troponin, in samples of body fluid. Meters may also be configured to determine the concentration of drugs, such as, for example, antibiotics (e.g., gentamicin, vancomycin, and the like), digitoxin, digoxin, drugs of abuse, theophylline, warfarin and the like. Such analytes can be monitored in blood, interstitial fluid, saliva, urine and other bodily fluids. It should also be noted that fewer or additional analyte measurement ranges from those described herein can be used. This includes not using ranges at all, but instead using, e.g., absolute values, formulas, lookup tables or similar concepts know to those skilled in the art to determine if or what type of alert, alarm, reminder or other indication should be made to the user for a particular analyte measurement result.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Each of the figures diagrammatically illustrates aspects of the invention. Of these:
[0016] FIG. 1 is plan view showing an exemplary embodiment of a glucometer system constructed according to aspects of the present invention;
[0017] FIG. 2 is a detail example of various alert and alarm displays, one of which is shown in the system of FIG. 1 ;
[0018] FIG. 3 is a graph depicting an example of how the glucose level of a user might vary over the course of a portion of a day.
[0019] FIG. 4 is a graph depicting the glucose levels shown in FIG. 3 with testing points added, some of which occur as a result of a reminder (alert or alarm).
[0020] Variation of the invention from that shown in the figures is contemplated.
DETAILED DESCRIPTION
[0021] The following description focuses on one variation of the present invention. The variation of the invention is to be taken as a non-limiting example. It is to be understood that the invention is not limited to particular variation(s) set forth and may, of course, vary. Changes may be made to the invention described and equivalents may be substituted (both presently known and future-developed) without departing from the true spirit and scope of the invention. In addition, modifications may be made to adapt a particular situation, material, composition of matter, process, process act(s) or step(s) to the objective(s), spirit or scope of the present invention.
[0022] FIG. 1 shows a top view of an exemplary analyte system 10 , a glucometer system in this particular embodiment. System 10 includes a handheld meter 12 and disposable test strip 14 . Test strip 14 can be inserted into or removed from test strip port 16 of meter 12 for physical and electrical interconnection therewith. Meter 12 includes an LCD display 18 for displaying information to the meter user, and buttons 20 , 22 and 24 for receiving input from the user.
[0023] In general, to take a blood glucose measurement with meter 12 , a user inserts a new test strip 14 into port 16 of meter 12 . Either before or after strip insertion into the meter, a user then lances a fingertip or other part of the body (i.e. an alternate site) to draw a small drop of blood 26 to the surface of the skin. The meter and strip are positioned over the drop of blood 26 so that one of the sample chamber ends 28 is touching the drop of blood 26 . While this particular example teaches the use of a side-fill strip, it should be noted that an end-fill, top-fill or other type of test strip may be utilized. Moreover, the analyte testing need not use a test strip at all. For instance, certain test meters may utilize a rotary test wheel for making multiple measurements, rather than individual test strips. In the present example, surface tension (wicking) automatically draws a small amount of blood 26 into the sample chamber and an electrochemical test is automatically performed by meter 12 to determine the glucose concentration in the blood 26 . The glucose level 30 is then displayed on meter 12 .
[0024] According to aspects of the present invention, an alert and/or alarm 32 can also be shown on display 18 indicating, for example, whether the current measurement falls within a predetermined range, such as an ideal glucose range, an upper or lower range of moderate concern or an upper or lower range of high concern.
[0025] Referring now to FIG. 2 , a further example of alert and alarm displays 32 is shown. A steeply downwardly inclined arrow 34 (e.g. about −60 to about −90 degrees) can be used to indicate a glucose reading in a lower range of high concern, such as below about 50 mg/dL. A moderately downwardly inclined arrow 36 (e.g. about −30 to about −45 degrees) can be used to indicate a glucose reading in a lower range of moderate concern, such as about 50 mg/dL to about 75 mg/dL. A horizontal arrow 38 (e.g. about 0 degrees) can be used to indicate a glucose reading in an ideal range, such as about 75 mg/dL to about 175 mg/dL. A moderately upwardly inclined arrow 40 (e.g. about 30 to about 45 degrees) can be used to indicate a glucose reading in an upper range of moderate concern, such as about 175 mg/dL to about 250 mg/dL. Finally, a steeply upwardly inclined arrow 42 (e.g. about 60 or about 90 degrees) can be used to indicate a glucose reading in an upper range of high concern, such as above about 250 mg/dL. As previously indicated above, various other visual elements, and/or audible or physical indicators can be used to provide the user with an alert or an alarm.
[0026] Referring now to FIG. 3 , an example of blood glucose values for a user is shown. Curve 100 depicts how the user's blood glucose might change with time over a portion of a day. In this example, the ideal range for the user is about 75 mg/dL to about 175 mg/dL, shown with reference numeral 110 and bounded by dashed lines 112 and 114 . The ranges of moderate concern are about 50 mg/dL to about 75 mg/dL (lower alert zone 116 , bounded by dashed lines 112 and 118 ) and about 175 mg/dL to about 250 mg/dL (upper alert zone 120 , bounded by dashed lines 114 and 122 ). The ranges of high concern are below about 50 mg/dL (lower alarm zone 124 , below dashed line 118 ) and above about 250 mg/dL (upper alarm zone 126 , above dashed line 122 .
[0027] In FIG. 3 the glucose values ( 100 ) begin at about 150 mg/dL, rise to about 195 mg/dL ( 101 ), fall to about 155 mg/dL ( 102 ), rise to about 270 mg/dL ( 103 ), fall to about 60 mg/dL ( 104 ), rise to about 90 mg/dL ( 105 ), fall to about 40 mg/dL ( 106 ), and end at about 100 mg/dL.
[0028] FIG. 4 shows the same blood glucose values 100 as FIG. 3 but adds the testing that was performed by that user, some of which occurs as a result of a reminder (alert and/or alarm and/or reminder). For example, after a light meal (snack) the user tests with a reading of 193 mg/dL ( 201 ) that falls in the upper alert zone ( 120 ). This reading may cause meter 12 to generate an alert to the user, e.g., flashing display, beep, or the like, that his or her glucose is in an upper level of moderate concern, as previously described above. The meter may alert the user substantially immediately after the determination of the reading in the upper alert zone, or sometime thereafter as described below. Regardless of whether the user is notified substantially immediately of a reading in an alert zone (or other zone of concern as described herein), the meter may also be configured to remind the user to perform a re-test after a predetermined amount of time following a reading in a zone of importance (alarm zone or alert zone). For example, after the above-described meter reading in upper alert zone 120 , a meter reminder may notify the user to perform a test after a predetermined amount of time, e.g., about 5 minutes, e.g., about 10 minutes, e.g., about 20 minutes, e.g., about 30 minutes, etc., and may periodically remind a user until a test is performed or until the reminder is cleared by the user. For example, the user may respond to the reading and alert (if alerted) with modest therapy and some time later (e.g., about 30 minutes), a reminder prompts the user to test, resulting in a reading of 160 mg/dL ( 202 ) that falls in the ideal zone ( 110 ).
[0029] Later, after a large meal the user tests with a reading of 268 mg/dL ( 203 ) that falls in the upper alarm zone ( 126 ). This reading causes meter 12 to generate an alarm to the user that his or her glucose is in an upper level of high concern. The user responds to the reading with an appropriate therapy and some time later (e.g. 20 minutes), a reminder prompts the user to test, resulting in a reading of 232 mg/dL ( 204 ) that falls in the upper alert zone ( 120 ). This reading causes meter 12 to generate an alert to the user that his or her glucose is in an upper level of moderate concern. The user may note that the previous therapy was appropriate and again, some time later (e.g. 30 minutes), a reminder prompts the user to test again, resulting in a reading of 156 mg/dL ( 205 ) that falls in the ideal zone ( 110 ) and confirms the previous therapy was appropriate.
[0030] Still later, after having exercised but not having eaten the user feels slightly symptomatic and tests with a reading of 61 mg/dL ( 206 ) that falls in the lower alert zone ( 116 ). This reading causes meter 12 to generate an alert to the user that his or her glucose is in a lower level of moderate concern. The user responds by eating a light meal (snack) and some time later (e.g. 25 minutes), a reminder prompts the user to test, resulting in a reading of 81 mg/dL ( 207 ) that falls in the ideal zone ( 110 ).
[0031] Yet later still, the user feels symptomatic and tests with a reading of 41 mg/dL ( 208 ) that falls in the lower alarm zone ( 124 ). This reading causes meter 12 to generate an alarm indicating that the glucose level is in a lower level of high concern. The user responds by eating a modest meal and some time later (e.g. 15 minutes), a reminder prompts the user to test, resulting in a reading of 63 mg/dL ( 209 ) that falls in the lower alert zone ( 116 ). This reading causes meter 12 to generate an alert indicating that the glucose level is now in a lower level of moderate concern. The user may note that the previous therapy (meal) was appropriate or may eat a small amount (snack) and again some time later (e.g. 25 minutes), a reminder prompts the user to test, resulting in a reading of 99 mg/dL ( 210 ) that falls in the ideal zone ( 110 ) and confirms the course of therapy was appropriate.
[0032] It should be noted that in this example, tests 201 , 203 , 206 and 208 were initiated by the user based on events known by the user to cause changes in blood glucose, or based on symptoms experienced by the user. More importantly, the user was prompted to perform tests 202 , 204 , 205 , 207 , 209 and 210 by a meter constructed according to aspects of the present invention. These prompts or timed reminders assist the user in performing appropriate tests in a timely manner. These tests in turn facilitate the user's important goal of keeping his or her blood glucose level in the ideal zone 110 to maintain the user's short-term and long-term health.
[0033] As for additional details pertinent to the present invention, materials and manufacturing techniques may be employed as within the level of those with skill in the relevant art. The same may hold true with respect to method-based aspects of the invention in terms of additional acts commonly or logically employed. Also, it is contemplated that any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein. Likewise, reference to a singular item, includes the possibility that there are plural of the same items present. More specifically, as used herein and in the appended claims, the singular forms “a,” “and,” “said,” and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The breadth of the present invention is not to be limited by the subject specification, but rather only by the plain meaning of the claim terms employed.
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An analyte measurement system is provided that can issue an alert or an alarm to a user when a measurement falls within a particular predetermined range. The system can also include a reminder for the user to perform additional tests at a predetermined time period after a measurement that falls within a predetermined range. Various visual, audible and physical alerts, alarms and reminders are disclosed. Methods associated with the use of the analyte measurement system are also covered.
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FIELD OF THE INVENTION
This invention relates to broadly defined adhesive latex formulations exhibiting antimicrobial properties. Such formulations comprise, as the only antimicrobial active ingredients, certain inorganic antimicrobial compounds, such as, preferably, metal-containing ion-exchange and/or zeolite compounds. The inventive latex formulations must also exhibit substantially uniform characteristics (such a similar viscosity and/or appearance throughout) in order to provide a functionally and aestheticially pleasing formulation for utilization within any number of applications. In order to provide such an inventive latex formulation, it has been found that compounding of all the base ingredients (polymer, antimicrobial agent, fillers) must be undertaken prior to the final thickening, step, which ultimately produces the desired latex. The specific method of producing such formulations is also encompassed within this invention.
DISCUSSION OF THE PRIOR ART
All U.S. Patents listed below are herein entirely incorporated by reference.
There has been a great deal of attention in recent years given to the hazards of bacterial contamination from potential everyday exposure. Noteworthy examples of such concern include the fatal consequences of food poisoning due to certain strains of Eschericia coli being found within undercooked beef in fast food restaurants; Salmonella contamination causing sicknesses from undercooked and unwashed poultry food products; and illnesses and skin infections attributed to Staphylococcus aureus, Klebsiella pneumoniae , yeast, and other unicellular organisms. With such an increased consumer interest in this area, manufacturers have begun introducing antimicrobial agents within various household products and articles. For instance, certain brands of polypropylene cutting boards, liquid soaps, etc., all contain antimicrobial compounds. The most popular antimicrobial for such articles is triclosan. Although the incorporation of such a compound within liquid or certain polymeric media has been relatively simple, other substrates, including the surfaces of textiles and fibers, have proven less accessible. Furthermore, triclosan includes chlorine ions which, upon dissociation, may release to the substrate surface. Such ions are potentially hazardous to humans, due to skin irritation upon contact, as well as within environmental effluents, and the like. Additionally, harmful microbes have shown, on occasion, an ability to develop an immunity to the bactericidal properties of triclosan. Also, surface treatments with triclosan have proven ineffective as well since such compounds are highly water soluble and are easily removed upon exposure to sufficient amounts of moisture and high temperatures. There thus remains a long-felt need to provide a short-and long-term effective, durable, and long-lasting antimicrobial agent for surface utilization within adhesive latex formulations. Of additional importance is the need to provide such formulations which, upon exposure to high temperature processing conditions (either in the production of or incorporation of such formulations within other applications, such as carpet backing, and the like) do not require the presence of organic bactericides which may result in the release of a certain volatile organic content (VOC) upon such high temperature processing.
One proposed latex has utilized metal ions for bactericidal properties, but also requires the presence of an organic bactericide to provide the desired level of antimicrobial activity. U.S. Pat. No. 5,736,591 to Dunn teaches the addition of certain metal ions, including copper, silver and any other Group Ib metals, as salts (such as silver nitrate, silver perchlorate, and the like) to latex formulations in combination with Such organic compounds as 2-methyl-4, 5-trimethylene-4-isothiazolin-3-one, to provide a bactericidal latex. No mention is made anywhere within this patent of the availability, much less, the capability of silver-based ion-exchange or zeolite compounds as potential antimicrobial agents. Nor is there any discussion of the ability of any such silver-based compounds providing effective antimicrobial activity without the need for any added organic bactericides.
Such specific silver-containing inorganic microbiocides (e.g., ion-exchange and/or zeolite compounds) have recently been developed and utilized as antimicrobial agents on and within a plethora of different substrates and surfaces. In particular, such microbiocides have been adapted for incorporation within plastic compositions and fibers in order to provide household and consumer products which inherently exhibit antimicrobial characteristics. Although such silver-based agents provide excellent, durable, antimicrobial properties, to date no teachings exist which teach or fairly suggest the presence of such inorganic compounds within adhesive latex fomulations. This is not surprising considering the difficulties which have been noted in attempting such an introduction of these large molecular weight, bulky, compounds within polymer latex formulations to begin with. For instance, such inorganic compounds may interfere with the desired adhesives qualities of the latex if and when such large molecules are present at the surface. One would anticipate that a large surface accumulation of such bulky compounds would reduce the potential surface-to-surface interaction required for the adhesive formulation to function properly. Furthermore, it has been found that the addition of such bulky compounds within already-compounded latex formulations is extremely difficult. The resultant composition generally exhibits discrete areas of concentrated, dark-colored, antimicrobial compound. Not only does this result in an unpleasing aesthetic appearance, but such a latex, being nonuniform in dispersion as well, may exhibit uneven adhesive properties, too. Although these problems exist, there is a desire to incorporate such silver-based inorganic antimicrobial agents within adhesive latex formulations in order to provide a regenerable, highly effective, long-lasting antimicrobial latex at, on, or within various different articles. Unfortunately, to date, no such antimicrobial adhesive latex or methods of production or use thereof have been accorded the latex industry by the pertinent prior art.
DESCRIPTION OF THE INVENTION
It is thus an object of the invention to provide a simple manner of producing an effective adhesive latex comprising, as the sole antimicrobial agent, at least one inorganic silver-based ion-exchange compound or zeolite compound. Another object of the invention is to provide an antimicrobial adhesive latex exhibiting a substantially uniform appearance and possessing no VOC content.
Accordingly, this invention encompasses an adhesive latex fomulation comprising at least one polymer constituent, at least one thickening agent (in order to provide a latex having a viscosity of, preferably, at least 4,000 cps at 25° C. and at 1 atmosphere), and at least one inorganic silver-based antimicrobial agent selected from the group consisting of silver-based ion-exchange compounds, silver-based zeolites, silver-based glasses, and any mixtures thereof, wherein said formulation does not include any VOC (due to the absence of any organic bactericide compounds, primarily). This invention also encompasses a method of producing such an antimicrobial adhesive latex formulation comprising the steps of (a) providing a polymer constituent, compounding said polymer constituent with an inorganic silver-based antimicrobial agent (as noted above) and a thickener, simultaneously, until the resultant composition exhibits a viscosity of, preferably, at least 4,000 cps at 25° C. and at 1 atmosphere.
The term adhesive latex is intended to encompass any thickened formulation of already-made polymer constituents which possesses a viscosity of at least viscosity of, preferably, at least 125,000 cps at 25° C. and at 1 atmosphere and which also exhibits an affinity for different surfaces which results in the ability to create a stationary interaction between the latex and the target surface without the needed presence of any other adhesive initiators, additives, compounds, or other compositions. Such latices are well known throughout the pertinent art (such as within U.S. Pat. No. 5,736,591) and may be utilized within any variety of applications which require extremely thick adhesives, including, without limitation, carpet backings, sealant compositions (for ceramic tiles, for example), and the like. The term polymer constituent is intended to encompass any polymeric material capable of being in latex form. Such constituents thus include, without limitation, olefins, acrylics, urethanes, vinylidene chlorides, vinyl acetates, vinyl pyridines, aromatics, silicones, and any copolymers thereof. Most preferably, the latex is a styrene butadiene rubber (SBR) latex, a polyurethane latex, a vinylidene chloride latex, a polyvinylidene chloride latex, a carboxylated SBR latex, and the like. Such polymer constituents within this invention include, without limitation, and preferably, HPL 8455NA (a vinylidene chloride) from Dow, and Reichold R101 (SBR rubber). The amount of polymer constituent present within the inventive latex ranges from about 10 to about 65% by weight of the total composition. Preferably, this amount is from about 20 to about 60%; more preferably from about 25 to about 50%; most preferably from about 30 to about 50%. It is common for such pre-prepared polymer constituents to include biocide agents solely for the purpose of preserving such compounds upon long-term storage.
Such latices arc preferably of high solids content to provide high adhesive properties. As such, the latex should be, as noted above, of rather high viscosity in order to stabilize the solid compounds in composition. Such a viscosity, as measured at 25° C. and at 1 atmosphere pressure, is at least 4,000 cps; preferably between about 4,500 and 25,000 cps; more preferably from about 5,000 cps to about 15,000 cps; and most preferably from about 5,000 cps to about 12,000 cps. The necessary thickener added to the polymer constituent is thus of prime importance. A thickener such as polyacrylate salt (sodium for example) is highly preferred, although any standard latex thickening agents may be utilized for this purpose. The amount of thickener is highly dependent on the desired target viscosity. Generally, then, the amount should be from about 0.005 to about 5% by weight of the total latex formulation; preferably from about 0.01 to about 3%; more preferably from about 0.015 to about 1%; and most preferably from about 0.02 to about 0.5%.
The term inorganic silver-based antimicrobial material is intended to encompass any such silver-conatining solid compound which is primarily inorganic in nature (some organic component is permitted, although the primary antimicrobial portion must be inorganic), is a solid at standard temperature and pressure, and which exhibits antimicrobial activity. Preferably, such material is a silver-based ion-exchange compound, a silver-based zeolite, or a silver-based glass, and any combinations thereof The preferred silver-based ion exchange material is an antimicrobial silver zirconium phosphate available from Milliken & Company, under the tradename ALPHASAN®. Other potentially preferred silver-containing solid inorganic antimicrobials in this invention is a silver-substituted zeolite available from Sinanen under the tradename ZEOMIC® AJ, or a silver-substituted glass available from Ishizuka Glass under the tradename IONPURE®, may be utilized either in addition to or as a substitute for the preferred species. Other possible compounds, again without limitation, are silver-based materials such as AMP® T558 and MICROFREE®, both available from DuPont, as well as JMAC®, available from Johnson Matheny. Generally, such a metal compound is added in an amount of from about 0.00001 to 10% by total weight of the particular latex composition; preferably from about 0.001 to about 5%; more preferably from about 0.01 to about 1%; and most preferably from about 0.1 to about 1.0%.
Other possible components within the inventive latex composition include water, (as a diluent), fillers, such as calcium carbonate (to provide strength and hardness to the latex, as well as to fill any “empty spaces” for a uniform strength dispersion), flame retardants, such as antimony oxide, available from Great Lakes Chemical, emulsifiers and/or surfactants (to provide more effective interaction with target surfaces and/or to provide foaming for easier application to target surfaces). Of these components, the fillers are generally added in large amounts within such latex formulations for the strength and hardness purposes.
As noted above, such an inventive comprises no organic bactericide compounds and thus does not include any appreciable VOC content originating from the antimicrobial component. This is of vital importance to ensure that utilization of such a latex does not result in the release of environmentally and/or physically hazardous organics, particularly upon exposure to high temperatures (e.g., above about 100° C.).
The inventive adhesive latex is preferably compounded with all of the required components simultaneously added together in order to provide the most uniform product, from both appearance and physical performance perspectives. Thus, simultaneous compounding of the polymer constituent, thickener, and silver-based inorganic antimicrobial agent are required (as well as the other potential additives) for this purpose. Adding such solid antimicrobial agents after compounding is extremely difficult without the production of highly undesirable discolorations (e.g., darkening, particularly if high temperatures are utilized for further processing).
The particular silver-based inorganic antimicrobial agent should exhibit an acceptable log kill rate after 24 hours in accordance with the AATCC Test Method 100-1983. Such an acceptable level log kill rate is tested for Staphylococcus aureus or Klebsiella pneumoniae of at least 0.1 increase over baseline. Alternatively, an acceptable level will exist if the log kill rate is greater than the log kill rate for non-treated (i.e., no solid inorganic antimicrobial added) latices (such as about 0.5 log kill rate increase over control, antimicrobial-free latices). Preferably these log kill rate baseline increases are at least 0.3 and 0.3, respectively for S. aureus and K. pneumoniae ; more preferably these log kill rates are 0.5 and 0.5, respectively; and most preferably these are 1.0 and 1.0, respectively. Of course, the high end of such log kill rates are much higher than the baseline, on the magnitude of 5.0 (99.999% kill rate). Any rate in between is thus, of course, acceptable as well. However, log kill rates which are negative in number are also acceptable for this invention as long as such measurements are better than that recorded for correlated non-treated latices. In such an instance, the antimicrobial material present within the latex at least exhibits a hindrance to microbe growth.
The preferred embodiments of these alternatives fabric treatments are discussed in greater detail below.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Examples of particularly preferred compounds within the scope of the present invention are set forth below.
Adhesive Latex Production
The preferred inventive adhesive latices were compounded in accordance with the Table below with all of the components admixed together. The resultant viscosity of each of these compositions are listed as ranges.
Adhesive Latex Formulations
Example 1
SBR Latex Production
Component
Amount added (in weight by pounds)
R101
27,254
Water
1,857
Calcium Carbonate
14,444
Anionic Surfactant
360
(froth aid)
Antimicrobial
(as listed below)
Sodium polyacrylate
1,100
Chemwet 1396-A
141
(penetrant surfactant)
The resultant compounded formulation exhibited a viscosity of approximately 5,500 cps.
Example 2
Vinylidene Chloride Latex Production
Component
Amount added (in weight by pounds)
HPL 8455NA
24,154
Water
1,900
Calcium Carbonate
15,983
Anionic Surfactant
495
(froth aid)
Antimicrobial
(as listed below)
Sodium polyacrylate
1,045
The resultant compounded formulation exhibited a viscosity of approximately 5,500 cps.
The Antimicrobial material tested was ALPHASAN®RC 5000 and RC 7000 and, for comparison purposes, Durotex 5000 (an isothiazoline-based bactericide from Rohm and Haas). The resultant latices were then utilized as carpet backing components during the production of carpet tiles which involved combining at least three carpet components together, namely the face fibers (e.g., pile fibers), the primary backing fabric (through which the face fiber is introduced), and the secondary backing fabric or a polyurethane foam backing or an olefinic-based resin The adhesive latex was introduced to the side of the primary backing fabric prior to with the secondary backing. Upon introduction the latex strongly adhered to the backing and, upon said subsequent contact, with the secondary backing. The resultant was a strongly integrated article as desired, The face fibers were then coated and into separate preparations of microbes, namely, S. aureus and K. pneumoniae . After an exposure of 24 hours, the carpet was then tested for log kill rates of such microbes in accordance with AATCC Test Method 100-1993. The results for each of the formulations noted above, in combination with the specific antimicrobial agents as noted above, are in tabular form below:
EXPERIMENTAL DATA TABLE
Log, Kill Rates for, S. aureus and K. pneumoniae
Log Kill Rate
Antimicrobial Type (% by weight)
for S. aureus
Latex
Composition #
1
ALPHASAN ® RC 5000 (0.12%)
1.05
1
ALPHASAN ® RC 5000 (0.25%)
0.62
1
ALPHASAN ® RC 7000 (0.12%)
1.80
1
ALPHASAN ® RC 7000 (0.25%)
2.30
2
ALPHASAN ® RC 5000 (0.33%)
1.44
2
ALPHASAN ® RC 5000 (0.66%)
1.52
2
ALPHASAN ® RC 7000 (0.33%)
0.77
2
ALPHASAN ® RC 7000 (0.66%)
0.90
(Comparative
Examples)
1
Durotex 5000 (0.20%)
0.28
1
Durotex 5000 (0.40%)
0.30
2
Durotex 5000 (0.33%)
0.10
2
Durotex 5000 (0.66%)
0.20
Thus, inventive adhesive latex exhibits excellent adhesive and antimicrobial properties.
There are, of course, many alternative embodiments and modifications of the present invention which are intended to be Included within the spirit and scope of the following claims.
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Broadly defined adhesive latex formula s exhibiting antimicrobial properties. Such formulations comprise certain antimicrobial compounds, such as, preferably, metal-containing ion-exchange and/or zeolite compounds, are provided. The inventive latex formulations must also exhibit substantially uniform characteristics (such a similar viscosity and/or appearance throughout) in order to provide a functionally and aestheticially pleasing formulation for utilization within any number of applications. In order to provide such an inventive latex formulation, it has been found that compounding of all the base ingredients (polymer, antimicrobial agent, fillers) must be undertaken prior to the final thickening step, which ultimately produces the desired latex. The specific method of producing such formulations is also encompassed within this invention.
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BACKGROUND OF THE INVENTION
1. Technical Field
The present invention relates to a system for providing an automotive vehicle with a correct blend of base and additive fuel stocks.
2. Disclosure Information
As governmental regulations pertaining to automotive exhaust emissions become ever more stringent, it is becoming necessary to provide fuels which are adapted to a particular vehicle being refueled. For example, it may be necessary to provide more highly oxygenated fuels to certain vehicles. With diesel engines, and other types of engines, it may be necessary to provide enriched fuels or auxiliary fluids such as water-borne urea additives which would, for example, be placed in a separate tank of a vehicle, so as to be available for an aftertreatment process within a vehicle's catalytic control system.
Another factor affecting fueling in the future will be the use of fuel cells which cannot operate with fuel additives such as detergents and anti-wear additives for fuel pump protection which are necessary for diesel and gasoline engines.
As a result of the varying fuel needs presented by future model vehicles, it would likely be necessary to burden the fuel infrastructure with the need to distribute many different types of blended fuels. However, a system according to the present invention avoids the need for distributing various types of blended fuels by providing a base fuel and additive system.
Another problem with requiring different types of fuels is that improper fueling becomes a possibility. It may be difficult for future consumers to know and specify exactly what fuel is needed for a vehicle. A system according to the present invention overcomes this problem.
Finally, in the event that an automotive emission control system has adaptable controls so that, for example, a change in the efficiency of the control system may be corrected through the use of a fuel having a specific additive, it is desirable to be able to communicate this change in the fueling need of the vehicle to the fueling station. A system according to the present invention accomplishes this need.
Although the Mobil Oil Corporation currently has an electronic transponder device which communicates with a fuel pump so as to identify the holder of a fuel or other type of credit card, no information is communicated regarding the fueling needs of the vehicle.
SUMMARY OF THE INVENTION
A system for fueling an automotive vehicle includes a dispensing subsystem for providing a plurality of fuel components to an automotive vehicle, a transmitter mounted on the vehicle for identifying the type of fuel required by the vehicle, and a fuel control and communication subsystem for communicating with the vehicle through the transmitter so as to determine the type of fuel required by the vehicle. The control and communication system operates a fuel dispensing subsystem so as to provide the vehicle with the required blend of fuel components.
It is an advantage of the present invention that misfueling of vehicles, i.e., providing a fuel which is not appropriate for the vehicle, may be avoided.
It is another advantage of the present invention that custom blended fuel will allow vehicle efficiency to be increased. For example, a vehicle may be operated with fuel having a precise octane level needed by the vehicle to operate the engine spark advance at the most efficient point without charging the vehicle operator for unneeded octane. This octane requirement will be determined by the vehicle's on-board engine controller and communicated with the fuel dispensing system according to one aspect of the present invention.
Other objects and features as well as advantages of the present invention will become apparent to the reader of this specification.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram of a system according to the present invention.
FIG. 2 is a block diagram illustrating a method of refueling according to the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
As shown in FIG. 1, engine controller 10, which is drawn from a class of engine controllers known to those skilled in the art and suggested by this disclosure, receives engine operating information from a variety of sensors 12. Such sensors may include, without limitation, sensors for engine speed, vehicle speed, throttle position, ambient air temperature, fuel composition, engine knock, and other sensors. Fuel composition may include a percentage of oxygenates, alcohols, and other types of fuel components. Sensors 12 may also include an NOx or other exhaust gas component sensor. Thus, engine controller 10 may sense knock or some other engine operating parameter and determine that the vehicle engine requires fuel having a greater or lesser octane. If such is the case, engine controller 10 will determine the desired value for octane and transmit this value to transmitter 14, wherein the value for octane, which is a blendable fuel characteristic, is stored. This is shown at block 30 of FIG. 2. Then, when the vehicle is brought to a filling station, the stored value for the desired blendable characteristic or property, in this case, octane, will be transmitted by transmitter 14, which may be either a transponder or other type of transmitter which is carried upon or housed within the vehicle. Transmitter 14 will transmit the value of the blendable characteristic to fuel control and communication subsystem 16, which would preferably be housed at a filling station. Fuel control and communication subsystem 16 will communicate with the vehicle as noted above through transmitter 14 so as to determine the type of fuel required by the vehicle. For example, in the case of octane, high octane fuel having octane in excess of 100, may be blended with lower octane fuel in the area of 85 octane or less so as to achieve a blend having a desired octane rating.
Other characteristics which could be handled with a system according to the present invention would be oxygenates, or special fuels needed by diesel engines, as opposed to a similar fuel which could be consumed by vehicles having fuel cells but which cannot tolerate the detergents and other anti-wear additives required by internal combustion engines.
According to another aspect of the present invention, engine controller 10 may also be used to specify auxiliary fluids such as urea containing fluids for use with NOx aftertreatment systems. In this case, controller 10 will keep track of the amount of the auxiliary fluid within a separate holding tank carried on the vehicle. And, controller 10 will advise the fluid control and communications subsystem in the event that additional auxiliary fluid is needed. Other auxiliary fluids could comprise, for example, water, or other types of fluids known to those skilled in the art and suggested by this disclosure.
Turning to FIG. 2, a method according to the present invention includes the determination of a fuel characteristic value at block 30. This value is stored at block 32 and downloaded to fuel control and communication subsystem 16 at block 34. At block 36, fuel control and communication subsystem 16 determines the blend of fuel components required to obtain the desired characteristic value. Finally, at block 38, control and communication system 16 commands dispensing system 18 to furnish fuel having the desired characteristic to vehicle fuel system 20.
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A system for fueling an automotive vehicle includes a transmitter mounted on the vehicle for identifying the type of fuel required by the vehicle and a fuel control and communication subsystem providing fuel which is blended to achieve the characteristics called for by the vehicle mounted transmitter.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to telescoping booms and more particularly to telescoping boom extensions and retraction systems.
2. Prior Art
Multi-section telescoping booms are well known to the art and include, for examle, three section booms having three nestled together boom sections one of which is stationary and two of which are extensible with the innermost boom section being extensible with respect to the intermediate boom section from a forward end of the intermediate boom section and the intermediate boom section being extensible with respect to the stationary boom section from a forward end of the stationary boom section.
Such devices have, in the past, included hydraulic or pneumatic cylinders which operate between the stationary boom section and one of the extensible boom sections. Although it is known to the art to attach one end of the cylinder to the stationary section and another end of the cylinder to the most extensible of the boom sections, since the amount of extension which can exist for an ordinary cylinder is less than twice its retracted length, such devices are not favored for three section booms.
In other embodiments, a plurality of hydraulic cylinders have been used with a first hydraulic cylinder connected between the stationary and the intermediate boom section and a second hydraulic cylinder connected between the intermediate and the most extensible boom section. Such constructions have a noticeable disadvantage in requiring two cylinders and further require complicated pressure hose connections to supply pressure to the separate cylinders.
In order to reduce the complexity of such devices, it has been known to utilize chains or cables connecting various boom sections. For the most part, such prior constructions using chains or cables generally mounted the chains or cables, at least in part, exteriorly of the boom section. This external mounting, in addition to giving a bad appearance left operating portions of the system exposed to the elements and unprotected from damage or abrasion during operation.
Additionally, where such chains or cables had been previously used, it was often necessary to provide a separate take-up reel controlling actuation and take-up of the cable. Thus two actuation systems were needed, one for the hydraulic system where that was used and a second for the cable system.
It would be an advance in the art to provide a system which did not rely upon any external chains or cables and which did not require any separate actuation systems but which eliminated the necessity of multiple pneumatic or hydraulic cylinders while allowing boom extension of an amount greater than twice the collapsed length of one cylinder.
SUMMARY OF THE INVENTION
My invention overcomes disadvantages inherent in the above described art. The invention is herewith disclosed in connection with a three section boom consisting of a stationary section, an intermediate extensible section and an inner, most extensible section. Hereinafter these sections will be referred to as stationary, intermediate and inner sections respectively.
Primary telescoping force is provided by an extensible member such as an hydraulic cylinder which is connected between the stationary member and the intermediate member. The hydraulic cylinder which consists of a cylinder together with telescoping piston rod is positioned interior of the inner section and has one end attached to the base end of the stationary section and a second, remote end attached to a channel member end remote from the base end. The channel member has an end adjacent the base end which is connected to the intermediate section at the base end of the intermediate section. Thus actuation of the hydraulic cylinder will cause movement of the intermediate section in or out of the stationary section.
Movement of the inner section is controlled by cables with each cable having one end anchored to the base end of the stationary section and the opposite end anchored to the stationary section adjacent its forward or free end. The cables pass from the base section outwardly towards the free end through the inner section. Adjacent the free end the cable passes around a sheave attached to the free end of the hydraulic cylinder and the returns towards the base end interior of the inner section. At the base end the cable then passes around a sheave attached to the base end of the intermediate section. The cable then extends towards the free end between the intermediate and stationary sections and is anchored adjacent the free end of the stationary section. A clamp member attached to the inner section adjacent the base end of the inner section clamps the cable to the inner section.
Although both ends of the cable remain stationarily attached to the stationary section of the boom, as the hydraulic cylinder is moved, the distance between the cable anchor on the base end of the stationary section and the sheave attached to the free end of the hydraulic cylinder increases. This increase in cable length for that stretch causes corresponding decrease in the length of the cable between the sheave around the free end of the cylinder and the clamp to the cable between the inner boom section and the cable. This causes movement of the clamp relative to both the stationary section and the intermediate boom section thereby causing extension of the inner boom section with respect to the intermediate section at the same time that the intermediate section is being extended with respect to the stationary section. The movement of the cable is such that there is synchronised movement of the boom sections. This movement is on a 1 to 1 ratio and is synchronised in both sections and is such that when the intermediate section is fully extended with respect to the base section, the inner section will be fully extended with respect to the intermediate section.
Upon reversal of the hydraulic cylinder occasioning a withdrawl of the intermediate section into the base section, the respective cable distance will again change. There will be an increase in the length of the portion of the cable between the free end of the stationary section and the sheave on the intermediate section which causes a relative decrease in the cable length between the base end of the stationary section and the sheave on the cylinder rod. This causes a relative movement of the cable stretch between sheave on the cylinder rod and the clamp between the cable and the inner boom section. Thus the inner boom section will be automatically withdrawn upon retraction of the intermediate boom section.
It can therefore be seen that my invention provides for automatic extension and retraction of the most extensible of the boom sections by means of a cable and sheave system located interiorly of the extensible boom which cable and sheave system automatically causes movement of the inner section of the boom in direct response to movement of the intermediate section of the boom with respect to the base section.
It is therefore an object of this invention to provide an improved telescoping boom assembly having at least two extensible boom sections and a stationary boom section.
It is another, more particular, object of this invention to provide an improved extensible boom system having three telescoping boom sections with an outer stationary boom section, an intermediate boom section extensible with respect to the outer boom section and an inner boom section extensible with respect to both the intermediate and outer booms whereby the inner boom section is the most extensible of the sections with movement of the inner boom controlled by a cable and sheave system located entirely interiorly of the boom assembly and with movement of the intermediate boom section controlled by a hydraulic cylinder having one end attached to the stationary boom section with a cylinder assembly intermediate portion extending through the inner boom section and terminating in a free end which has a channel member attached thereto, the channel member being positioned interior of the inner boom section and being attached to the intermediate section adjacent a base end of the intermediate section with a cable length having an end anchored to the stationary section adjacent a base end of the stationary section, the cable extending from the base end anchor interiorly of the innermost section to the free end of the cylinder thence around a sheave and back through the innermost section towards a base end thereof thence around a sheave attached adjacent a base end of the intermediate section thence between the intermediate and stationary sections to an anchor adjacent the free end of the stationary section, the cable clamped to the inner boom section and controlling extension and retraction thereof.
Other objects, features and advantages of the invention will be readily apparent from the following description of a preferred embodiment thereof, taken in conjunction with the accompanying drawings, although variations and modifications may be effected without departing from the spirit and scope of the novel concepts of the disclosure, and in which:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagrammatic, perspective view of an extensible working platform vehicle equipped with the boom assembly of this invention.
FIG. 2 is a fragmentary perspective view of the boom assembly of this invention with portions thereof broken away to show underlying portions and with interior portions illustrated by broken lines.
FIG. 3 is a cross section of the boom assembly of this invention taken generally along the lines III--III of FIG. 2.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 illustrates an extensible platform vehicle 10 which includes a vehicle base section 11 having wheels 12 which may be articulatable and powered. A boom base 13 is carried on the vehicle base 11 through a rotating connection 14 allowing the boom base 13 to rotate in a horizontal plane with respect to the base 11. A boom assembly 15 is pivotably mounted as at 16 to the boom base 13 and may be elevated or lowered with respect thereto by means such as hydraulic jacks 17. The boom 15 has a base end portion 22 adjacent the pivot 16 and a free end portion 23 remote from the pivot. A work platform 18 may be attached to the free end portion 23 and be capable of supporting one or more workers and associated equipment.
Normally the platform 18 is attached to the free end portion 23 through an articulated connection allowing the platform to be automatically or manually leveled irrespective of the angle of inclination of the boom with respect to the horizontal. Additionally the platform 18, as well as the base 13 may be equipped with suitable controls for raising or lowering the boom, for telescoping the boom, for rotating the boom base 13 on the vehicle base 11, and if desired, for driving and steering the vehicle base 11.
Extension of the boom is accommodated through three telescoping sections including a stationary section 19 having a base end attached to the pivot 16, an intermediate section 20 telescoped in the base section 19 and an inner section 21 telescoped in the intermediate section 20. The inner section 21 thus constitutes the most extensible of the sections in that it can be telescoped outwardly the greatest distance with respect to the boom base 13.
FIG. 1 illustrates various elevations of the boom from a depressed elevation 25 through a horizontal elevation 26 to a raised elevation 27.
FIG. 2 illustrates the boom assembly 15 in greater detail showing the nestling of the inner boom section 21 in the intermediate boom section 20 which in turn is nestled in the stationary boom section 19.
The stationary boom section 19 has a base end 30 which is attached to the pivot 16 and a free end 31 remote from the base end. In the illustrated embodiment the base section, the intermediate section and the inner section are generally rectangular in cross section and are open at both longitudinal ends. When in the collapsed or retracted position, there is a space 32 between the base end 33 of the intermediate section 20 and the base end 30 of the stationary section 19. There is also a space between the base end 34 of the inner section 21 and the base end 33 of the intermediate section 20.
Conversely the free end 35 of the inner section 21 projects beyond the free end 36 of the intermediate section and the free end 31 of the stationary section. In the embodiment illustrated the free end of the intermediate section has been broken away.
Adjacent the base end 30 of the stationary section 19 a cross bar 40 spans the interior of the rectangular base section. The cross bar 40 is positioned off center of the base section and forms an anchor block for a power cylinder 41 such as a pneumatic cylinder. The power cylinder extends longitudinally of the boom assembly interior of the inner section and, in a known manner, includes a piston rod 42 which terminates interior of the inner section adjacent the free end 35 thereof but which is not affixed to the inner section. A channel member 44, which in the illustrated embodiment is a rectangular cross section hollow member surrounds the pneumatic cylinder 41 and piston rod 42 and extends from the free end of the piston rod 42 to adjacent the base end 33 of the intermediate section 20. Overlapping brackets 45 on the base end 33 of the intermediate section and on the base end 46 of the channel member 44 attach the channel member 44 to the intermediate section 20. Attachment may be by means of bolts or the like.
The channel member 44 is attached to the free end of the cylinder's piston rod as by means of an axle member 48 which passes through openings in side walls of the channel member 44 and through an eye opening in the end of the cylinder rod. Sheaves 49 and 50 may be attached to the shaft 48 exterior of the channel member 44 and interior of the inner section 21.
Thus as the hydraulic cylinder 41 is activated to extend the piston rod 42 out of the free end of the hydraulic cylinder, movement of the piston rod is transferred to movement of the channel member 44 through the shaft connection 48. Movement of the channel member 44 causes movement of the intermediate member 20 by means of the connection 45. In this manner, although the hydraulic cylinder is located interior of the inner section 21 it causes direct movement, not of the inner section 21 but of the intermediate section 20. The connection 45 with the bracket member 44 is possible due to the extension of the base end 33 of the intermediate member beyond the base end 34 of the inner member in the direction of the base end 32 of the stationary member when the boom is fully collapsed.
In order to cause movement of the inner member 21 cables 50 are provided. Each of the cables 50 has a base end 51 anchored to the cross bar 40 in the base end of the stationary member and has a free end 52 anchored to a cross bar 53 at the free end 31 of the stationary section 19. The cable 50 has a first stretch 55 which extends from the anchor end 51 to the free end of the piston rod 42 then around one of the sheaves 49, 50. The cable 50 then has an intermediate stretch 56 extending from the sheave 49, 50 back towards the base end to a sheave 54 projecting from the base end 33 of the intermediate section. A third stretch 56 of the cable 50 extends from the sheave 54 to the free end anchor 52. The first and intermediate stretches 55 and 56 project longitudinally interior of the inner section 21. The third stretch 57 extends longitudinally between the intermediate section 20 and the stationary section 19.
The intermediate stretch 56 is attached to the inner section 21 adjacent the base end thereof 34 by means of a clamp member 60.
In the preferred embodiment two cables 50 are used located on either side of the centrally disposed pneumatic cylinder 41 with one cable passing around the sheave 49 and another cable passing around the sheave 50. In this instance there are two sheaves 54 and 54a attached to the base end 33 of the intermediate section 20. The inner section 21 is thus firmly clamped adjacent its base end 34 to one point of the intermediate stretch 56 of each of the cables. As the sheave 49 or 50 moves with respect to the stationary section 19 by extension of the piston rod 42, the corresponding sheave 54, 54a will also be moved an equal distance with respect to the stationary section. This will cause a lengthening of the cable stretch 55 and a shortening of the cable stretch 57. This relative lengthening and shortening of the stretches 55 and 57 requires a movement of the cable in intermediate stretch 56 since the position of the sheaves 49, 50 and 54, 54a are fixed with respect to one another. Movement of the cable within stretch 56 will, because of the anchors 60 cause an equal distance movement of the inner secton 21. The distance the inner section will be moved with respect to the intermediate section is one to one which, however, translates to a 2 to 1 movement with respect to the stationary section. In this manner as the intermediate section is moved relative to the stationary section under influence of the hydraulic cylinder, the inner section will be moved relative to the intermediate section.
The action is the same upon contraction of the system from an extended boom position by withdrawal of the piston rod 42 into the cylinder 41. In such a movement the cable stretch 55 will become shorter whereas the cable stretch 57 will become longer again requiring a corresponding movement of the cable in constant length intermediate stretch 56.
In order to allow relative movement of the channel member 44 with respect to the inner section, a spacer member 70 is attached to the bracket member. The spacer member 70 is, in the preferred embodiment, U-shaped having outturned flanges 71 on the free ends of the legs of the U with the bight of the U attached to a side wall of the bracket member 44 as illustrated in FIG. 3. Thus the outturned flanges 71 form slide surfaces and the hollow interior 72 can function as a conduit for control wires and the like between the platform and the boom base 13. Wear pads 73 can be positioned between the bracket member 44 and the inner face of the inner section 21 on the opposite side of the inner section 21 from the member 70. Additionally wear pads 74 can be provided between the inner section and the intermediate section and between the intermediate section and the stationary section. Preferably the wear pads 74 are positioned on all four sides of each of the sections and in order to allow telescoping of the sections without cocking of the one section within the other, the wear pads 74 are properly disposed on the inside faces of the intermediate and stationary sections adjacent their free ends and on the outside faces of the intermediate and inner sections adjacent their base ends.
It can therefore be seen from the above that my invention provides method and means for extending the boom sections of a three section boom including a hydraulic cylinder connection between a stationary boom section and an intermediate boom section with the hydraulic cylinder positioned interior of an inner boom section and a cable connection between stationary, intermediate and inner sections and the hydraulic cylinder causing movement of the inner section relative to the intermediate and base sections such that the inner section will be automatically telescoped inwardly or outwardly of the intermediate section in direct response to movement of the intermediate section relative to the stationary section under the influence of the hydraulic system. All of the drive assemblies including the hydraulic section, the cables and associated sheaves are positioned interior of the boom assembly where they are protected from the elements and from abrasion and wear during usage.
Although I have described my invention in connection with rectangular booms and involving two cables with a hydraulic cylinder, it is to be understood that variations of this assembly can be provided including, for example, hexagonal, octagonal or the like boom sections, one, three or more cables or cables which are made up of two or more sections or other variants.
Although the teachings of my invention have herein been discussed with reference to specific theories and embodiments, it is to be understood that these are by way of illustration only and that others may wish to utilize my invention in different designs or applications.
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An extension and retraction mechanism for a three section extensible boom is disclosed utilizing an internally disposed hydraulic cylinder connected between a stationary boom section and an intermediate boom section with a cable connection located entirely interior of the boom having opposite ends anchored to opposite ends of the stationary section with the cable routed around sheaves on the moving end of the hydraulic cylinder and a base end of the intermediate boom section with a cable attachment to the base end of the inner boom section, the inner boom section being the most extensible boom section.
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BACKGROUND OF THE INVENTION
This application claims priority from provisional application Ser. No. 60/286,567, filed on Apr. 26, 2001, the entire disclosure of which is hereby incorporated by reference.
Recent studies with the selective 5HT 1A antagonist WAY-100635 have confirmed a role for 5-HT 1A receptors in learning and memory. Carli et. al. (Neuropharmacology (1999), 38(8), 1165-1173) demonstrated that WAY-100635 prevented the impairment of spatial learning caused by intrahippocampal injection of 3-[(R)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP), a competitive NMDA receptor antagonist, in a two-platform spatial discrimination task. Boast et. al. (Neurobiol. Learn. Mem. (1999), 71(3) 259-271) found that WAY-100635 significantly reduced the cognitive impairment induced by the non-competitive NMDA antagonist MK801, as determined by the performance of rats trained on a delayed nonmatching to sample radial arm maze task. Menesis et. al. (Neurobiol. Learn. Mem. (1999), 71(2) 207-218) showed that post-training administration of WAY-100635 reversed the learning deficit induced by scopolamine, a cholinergic antagonist, in an autoshaping learning task. Novel 5-HT 1A antagonists would be useful for this and other uses.
DESCRIPTION OF THE INVENTION
In accordance with this invention, there is provided a group of novel compounds of the formula I:
wherein
R 1 is hydrogen, halo, cyano, carboxamido, carboalkoxy of two to six carbon atoms, trifluoromethyl, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyloxy of 2 to 6 carbon atoms, amino, mono- or di-alkylamino in which each alkyl group has 1 to 6 carbon atoms, alkanamido of 2 to 6 carbon atoms, or alkanesulfonamido of 1 to 6 carbon atoms;
R 2 is hydrogen, hydroxy, halo, amino, mono- or di-alkylamino in which each alkyl group has 1 to 6 carbon atoms, or alkyl of one to six carbon atoms;
X is N or CR 3 ;
Y is N or CH;
R 3 is hydrogen or alkyl of one to six carbon atoms;
Z is pyrrolidine, piperidine, homopiperidine, morpholine, thiomorpholine,
R 4 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 3 to 6 carbon atoms or alkynyl or 3 to 6 carbon atoms;
Ar is phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, furyl, or thienyl, each optionally substituted;
R 5 is hydroxy, cyano or carboxamido and R 6 is Ar; or
R 5 is hydrogen and R 6 is benzoyl, 1-benzimidazol-2-one, benzoisothiazole, benzisoxazole, each optionally substituted, or —(CH 2 ) m Q;
m is 0 to 4; and
Q is Ar,
or a pharmaceutically acceptable salt thereof.
In some embodiments of the invention, R 1 is hydrogen, halo, trifluoromethyl, alkyl of one to six carbon atoms, alkoxy of one to six carbon atoms, amino, mono- or di-alkylamino in which each alkyl group has one to six carbon atoms. In still more preferred embodiments of the invention R 1 is hydrogen, halo, trifluoromethyl, alkyl of one to six carbon atoms or alkoxy of one to six carbon atoms.
In other preferred embodiments of the invention, R 2 is hydrogen, amino, mono- or di-alkylamino in which each alkyl group has one to six carbon atoms, or alkyl of one to six carbon atom. In more preferred embodiments of the invention R 2 is hydrogen, or alkyl of one to six carbon atom.
X and Y are each preferably each CH.
In some preferred embodiments of the invention, R 1 is hydrogen, halo, trifluoromethyl, alkyl of one to six carbon atoms, alkoxy of one to six carbon atoms, amino, mono- or di-alkylamino in which each alkyl group has one to six carbon atoms; R 2 is hydrogen, amino, mono- or di-alkylamino in which each alkyl group has one to six carbon atoms, or alkyl of one to six carbon atom, and Z is a radical of formula II.
Still more preferably R 1 is hydrogen, halo, trifluoromethyl, alkyl of one to six carbon atoms or alkoxy of one to six carbon atoms; R 2 is hydrogen, or alkyl of one to six carbon atom, X and Y are CH, and Z is a radical of formula II.
In other preferred embodiments of the invention, R 1 is hydrogen, halo, trifluoromethyl, alkyl of one to six carbon atoms, alkoxy of one to six carbon atoms, amino, mono- or di-alkylamino in which each alkyl group has one to six carbon atoms; R 2 is hydrogen, amino, mono- or di-alkylamino in which each alkyl group has one to six carbon atoms, or alkyl of one to six carbon atom, and Z is a radical of formula III, R 5 is hydroxy and R 6 is Ar; or R 5 is hydrogen and R 6 is benzoyl, 1-benzimidazol-2-one, benzoisothiazole, benzisoxazole, each optionally substituted, or —(CH 2 ) m Q in which m and Q are defined above.
Still more preferably R 1 is hydrogen, halo, trifluoromethyl, alkyl of one to six carbon atoms or alkoxy of one to six carbon atoms; R 2 is hydrogen, or alkyl of one to six carbon atom, X and Y are CH; Z is a radical of formula III, R 5 is hydroxy and R 6 is Ar; or R 5 is hydrogen and R 6 is benzoyl, 1-benzimidazol-2-one, benzoisothiazole, benzisoxazole, each optionally substituted, or —(CH 2 ) m Q and m is 0 or 1.
In yet other embodiments of the invention, R 1 is hydrogen, halo, trifluoromethyl, alkyl of one to six carbon atoms, alkoxy of one to six carbon atoms, amino, mono- or di-alkylamino in which each alkyl group has one to six carbon atoms; R 2 is hydrogen, amino, mono- or di-alkylamino in which each alkyl group has one to six carbon atoms, or alkyl of one to six carbon atom, and Z is a radical of formula IV.
Still more preferably R 1 is hydrogen, halo, trifluoromethyl, alkyl of one to six carbon atoms or alkoxy of one to six carbon atoms; R 2 is hydrogen, or alkyl of one to six carbon atom, X and Y are CH; and Z is a radical of formula IV.
It is preferred in still other embodiments of the invention that Z is a radical of formula II or III.
Where a substituent is “substituted” as used herein it may include from 1 to 3 substituents selected from hydrogen, halo, cyano, carboxamido, carboalkoxy of two to six carbon atoms, trifluoromethyl, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyloxy of 2 to 6 carbon atoms, amino, mono- or di-alkylamino in which each alkyl group has 1 to 6 carbon atoms, alkanamido of 2 to 6 carbon atoms, or alkanesulfonamido of 1 to 6 carbon atoms.
This invention relates to both the R and S stereoisomers of the aminomethyl-2,3-dihydro-1,4-dioxino[2,3-f]quinolines, -quinazolines or quinoxalines as well as to mixtures of the R and S stereoisomers. Throughout this application, the name of the product of this invention, where the absolute configuration of the aminomethyl-2,3-dihydro-1,4-dioxino[2,3-f]quinolines, -quinazolines or quinoxalines is not indicated, is intended to embrace the individual R and S enantiomers as well as mixtures of the two. In some preferred embodiments of the present invention the S stereoisomer is preferred.
Where a stereoisomer is preferred, it may, in some embodiments be provided substantially free of the corresponding enantiomer. Thus, an enantiomer substantially free of the corresponding enantiomer refers to a compound which is isolated or separated via separation techniques or prepared free of the corresponding enantiomer. Substantially free, as used herein means that the compound is made up of a significantly greater proportion of one stereoisomer. In preferred embodiments the compound is made up of at least about 90% by weight of a preferred stereoisomer. In other embodiments of the invention, the compound is made up of at least about 99% by weight of a preferred stereoisomer. Preferred stereoisomers may be isolated from racemic mixtures by any method known to those skilled in the art, including high performance liquid chromatography (HPLC) and the formation and crystallization of chiral salts or prepared by methods described herein. See, for example, Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen, S. H., et al., Tetrahedron 33:2725 (1977); Eliel, E. L. Stereochemistry of Carbon Compounds (McGraw-Hill, NY. 1962); Wilen, S. H. Tables of Resolving Agents and Optical Resolutions p. 268 (E. L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, Ind. 1972).
Alkyl as used herein refers to an aliphatic hydrocarbon chain and includes straight and branched chains such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neo-pentyl, n-hexyl, and isohexyl. Lower alkyl refers to alkyl having 1 to 3 carbon atoms.
Alkanamido as used herein refers to the group R—C(═O)—NH— where R is an alkyl group of 1 to 5 carbon atoms.
Alkanoyloxy as used herein refers to the group R—C(═O)—O— where R is an alkyl group of 1 to 5 carbon atoms.
Alkanesulfonamido as used herein refers to the group R—S(O) 2 —NH— where R is an alkyl group of 1 to 6 carbon atoms.
Alkoxy as used herein refers to the group R—O— where R is an alkyl group of 1 to 6 carbon atoms.
Carboxamido as used herein refers to the group —CO—NH 2 .
Carboalkoxy as used herein refers to the group R—O—C(═O)— where R is an alkyl group of 1 to 5 carbon atoms.
Halogen (or halo) as used herein refers to chlorine, bromine, fluorine and iodine.
Pharmaceutically acceptable salts are those derived from such organic and inorganic adds as: acetic, lactic, citric, cinnamic, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, oxalic, propionic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, glycolic, pyruvic, methanesulfonic, ethanesulfonic, toluenesulfonic, salicylic, benzoic, and similarly known acceptable acids.
Specific compounds of the present invention are:
8-[2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl]-1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one;
8-{[8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one;
1-(1-{[8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-piperidin-4-yl)-1,3-dihydro-2H-benzimidazol-2-one;
8-methyl-2-(piperidin-1-ylmethyl)-2,3-dihydro[1,4]dioxino[2,3-f]quinoline;
(4-fluorophenyl)(1-{[8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-4-piperidinyl)methanone;
1-{[8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}4-[3-(trifluoromethyl)phenyl]-4-piperidinol;
1-{[8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-4-phenyl-4-piperidinecarbonitrile;
8-methyl-2-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methyl}-2,3-dihydro[1,4]dioxino[2,3-f]quinoline;
8-{[8-ethyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one; or pharmaceutically acceptable salts thereof.
The 2-azaheterocyclylmethyl-2,3-dihydro-1,4-dioxino[2,3-f]quinolines in which R 2 is H are prepared as illustrated below. Specifically, the appropriately substituted nitroguaiacol is alkylated with allyl bromide in the presence of a suitable base such as sodium hydride and then demethylated by a reagent such as sodium hydroxide. The resulting 4-nitro-2-allyloxyphenol is then alkylated with glycidyl
tosylate or an epihalohydrin in the presence of a base such as sodium hydride and heated in a high boiling solvent such as mesitylene or xylene to effect both rearrangement of the allyl group and cyclization of the dioxan ring. The resulting primary alcohol is converted to the tosylate by reaction with p-toluenesulfonyl chloride in the presence of a tertiary amine or pyridine, or alternatively to a halide by reaction with carbon tetrabromide or carbon tetrachloride in combination with triphenylphosphine. The allyl side chain is then isomerized by treatment with catalytic bis-acetonitrile palladium (II) chloride in refluxing methylene chloride or benzene. Allylic oxidation with selenium dioxide in refluxing dioxane/water gives the o-nitrocinnamaldehyde, which upon reduction with iron in acetic acid cyclizes to the 2,3-dihydro-1,4-dioxino[2,3-f]quinoline-2-methyltosylate or halide. Replacement of the tosylate or halide with the appropriately substituted azaheterocycle (Z—H) in some high boiling solvent such as dimethyl sulfoxide gives the title compounds of the invention.
The 2-azaheterocyclylmethyl-2,3-dihydro-1,4-dioxino[2,3-f]quinolines of the invention in which R 2 is alkyl may be prepared from the nitro olefin described above in the following manner. The rearranged olefin is treated sequentially with ozone and a tertiary amine or with osmium tetroxide and sodium periodate to give the O-nitrobenzaldehyde. Condensation with the appropriate
triphenylphosphoranylidene ketone under Wittig conditions gives the o-nitrostyryl ketone, which upon reduction by iron in acetic acid, cyclizes to the corresponding 2,3-dihydro-1,4-dioxino[2,3-f]quinoline-2-methyltosylate. Replacement of the tosylate with the appropriately substituted azaheterocycle as above gives the title compounds of the invention. Substitution of trimethyl phosphonoacetate for the triphenylphosphoranylidene ketone in the Wittig procedure above, followed by reduction of the nitro group with tin (II) chloride and cyclization in acid gives the compounds of the invention in which R 2 is hydroxy. Alkylation of this hydroxy derivative by a suitable alkyl halide or tosylate in the presence of base gives the compounds of the invention in which R 2 is alkoxy. Treatment of the hydroxy derivative with an inorganic acid chloride such as phosphoryl chloride or bromide gives the compounds of the invention in which R 2 is halo. Substitution of diethyl cyanomethylphosphonate for the triphenylphosphorylidene ketone in the Wittig procedure above, followed by reduction of the nitro group with tin (II) chloride and cyclization in acid gives the compounds of the invention in which R 2 is amino.
Compounds of the invention in which R 1 is attached to position 6 of the 2,3-dihydro-1,4-dioxino[2,3-f]quinoline may be alternatively prepared by a variation of the Skraup quinoline synthesis according to the scheme below. The appropriately substituted benzodioxan methyltosylate is nitrated under standard conditions with nitric acid in a solvent such as dichloroethane and the resulting nitro
compound reduced by treatment with hydrogen in the presence of a catalyst such as platinum on sulfide carbon. Treatment of the resulting aniline with acrolein in the presence of hydrogen chloride and an oxidant such as p-chloranil or naphthoquinone gives the corresponding 2,3-dihydro-1,4-dioxino[2,3-f]quinoline. Replacement of the tosylate with the appropriately substituted azaheterocycle as above gives the title compounds of the invention.
The 2-azaheterocyclylmethyl-2,3-dihydro-1,4-dioxino[2,3-f]quinazolines of the invention are prepared as illustrated below. The o-nitrobenzaldehyde described above is converted to the oxime by
treatment with hydroxylamine hydrochloride in the presence of a suitable base such as sodium acetate and the nitro group reduced to the amine by hydrogenation over palladium on carbon. Cyclization to the quinazoline N-oxide is effected by treatment at reflux with the appropriate ortho ester according to the method of Ostrowski (Heterocycles, vol. 43, No. 2, p. 389, 1996). The quinazoline N-oxide may be reduced to the quinazoline by a suitable reducing agent such as hydrogen over Raney-nickel. Alternatively, an extended period of reflux in the ortho ester gives the reduced quinazoline directly via a disproportionation reaction and the 2,3-dihydro-1,4-dioxino[2,3-f]quinazoline-2-methyltosylate or halide may be isolated by column chromatography. Replacement of the tosylate or halide with the appropriately substituted azaheterocycle in some high boiling solvent such as dimethyl sulfoxide gives the title compounds of the invention.
The 2-azaheterocyclylmethyl-2,3-dihydro-1,4-dioxino[2,3-f]quinoxalines of the invention are prepared as illustrated below. The o-nitrobenzaldehyde described above is oxidized to the o-nitrobenzoic acid by a suitable oxidant such as chromium trioxide (Jones' oxidation) or sodium chlorite and the acid converted to the o-nitroaniline with diphenylphosphoryl azide (DPPA) in the presence of a tertiary base such as diisopropylethylamine. Reduction of the resulting nitroaniline to the diamine with hydrogen and
palladium on carbon and cyclization by treatment with the appropriate dicarbonyl compound (for example, glyoxal, 2,3-butanedione, 3,4-hexanedione) gives the 2,3-dihydro-1,4-dioxino[2,3-f]quinoxaline-2-methyltosylate or halide. Replacement of the tosylate or halide with the appropriately substituted azaheterocycle in some high boiling solvent such as dimethyl sulfoxide gives the title compounds of the invention.
The o-nitrobenzaldehyde used in the chemistry described above may be alternatively prepared as shown below. The appropriate mono-allylated catechol is elaborated with glycidyl tosylate as described above and rearranged in refluxing mesitylene. Cyclization to the benzodioxan methanol is
effected by treatment with sodium bicarbonate in ethanol and the alcohol is converted to the tosylate or halide as described above. After rearrangement of the double bond by treatment with catalytic bis-acetonitrile palladium (II) chloride in refluxing methylene chloride and cleavage with ozone or osmium tetroxide/sodium periodate as described above, the resulting aldehyde is regioselectively nitrated with a combination of nitric acid and tin (IV) chloride.
The guaiacols, catechols, benzodioxan methyltosylates and azaheterocycles appropriate to the above chemistry are known compounds or can be prepared by one schooled in the art. The compounds of the invention may be resolved into their enantiomers by conventional methods or, preferably, the individual enantiomers may be prepared directly by substitution of (2R)-(−)-glycidyl 3-nitrobenzenesulfonate or tosylate (for the S benzodioxan methanamine) or (2S)-(+)-glycidyl 3-nitrobenzenesulfonate or tosylate (for the R enantiomer) in place of epihalohydrin or racemic glycidyl tosylate in the procedures above.
High affinity for the serotonin 5-HT 1A receptor was established by testing the claimed compound's ability to displace [ 3 H] 8-OH-DPAT (dipropylaminotetralin) from the 5-HT 1A serotonin receptor following a modification of the procedure of Hall et al., J. Neurochem. 44, 1685 (1985) which utilizes CHO cells stably transfected with human 5-HT 1A receptors. The 5-HT 1A affinities for the compounds of the invention are reported below as K i 's.
Antagonist activity at 5-HT 1A receptors was established by using a 35 S-GTPγS binding assay similar to that used by Lazareno and Birdsall (Br. J. Pharmacol. 109: 1120, 1993), in which the test compound's ability to affect the binding of 35 S-GTPγS to membranes containing cloned human 5-HT 1A receptors was determined. Agonists produce an increase in binding whereas antagonists produce no increase but rather reverse the effects of the standard agonist 8-OH-DPAT. The test compound's maximum inhibitory effect is represented as the I max , while its potency is defined by the IC 50 .
The results of the two standard experimental test procedures described in the preceding two paragraphs were as follows:
5-HT 1A
Receptor Affinity
5-HT 1A Function
Compound
KI (nM)
IC 50 (nM) (I max )
Example 1
1.44
55.0 (100)
Example 2
1.79
64.0 (100)
Example 3
3.08
66.0 (85.0)
Example 4
51.04
483.0 (100)
Example 5
18.53
Example 6
6.94
Example 7
76.08
444.90 (50)
Example 8
7.91
Example 9
2.79
The compounds of this invention have potent affinity for and antagonist activity at brain 5-HT 1A serotonin receptors. The compounds of the invention are thus exceedingly interesting for the treatment of cognitive dysfunction such as is associated with mild cognitive impairment (MCI) Alzheimer's disease and other dementias including Lewy Body, vascular, and post stroke dementias. Cognitive dysfunction associated with surgical procedures, traumatic brain injury or stroke may also be treated in accordance with the present invention. Further, compounds of the present invention may be useful for the treatment of diseases in which cognitive dysfunction is a co-morbidity such as, for example, Parkinson's disease, autism and attention deficit disorders.
Compounds of the present invention are also useful for treating cognitive deficits due to CNS disorders such as schizophrenia, (and other psychotic disorders such as paranoia and mano-depressive illness). The compounds are also useful for the treatment of disorders related to excessive serotonergic stimulation such as anxiety (e.g. generalized anxiety disorders, panic attacks, and obsessive compulsive disorders), aggression and stress. In addition, compounds of the present invention may be useful for the treatment of various physiological conditions such as Tourette's syndrome, migraine, autism, attention deficit disorders and hyperactivity disorders, sleep disorders, social phobias, pain, thermoregulatory disorders, endocrine disorders, urinary incontinence, vasospasm, stroke, eating disorders such as for example obesity, anorexia and bulimia, sexual dysfunction, and the treatment of alcohol, drug and nicotine withdrawal which are known to be, at least in part, under serotonergic influence. Finally, recent clinical trials employing drug mixtures (e.g. fluoxetine and pindolol) have demonstrated a more rapid onset of antidepressant efficacy for a treatment combining SSRI (serotonin selective reuptake inhibitor) activity and 5HT1A antagonism (Blier and Bergeron, 1995; F Artigas, et al., 1996, M. B. Tome et al., 1997). The compounds of the invention are thus interesting and useful as augmentation therapy in the treatment of depressive illness.
Thus the present invention provides methods of treating, preventing, inhibiting or alleviating each of the maladies listed above in a mammal, preferably in a human, the methods comprising providing a pharmaceutically effective amount of a compound of this invention to the mammal in need thereof.
The present invention also provides methods of augmenting the treatment of depression by providing a mammal, preferably a human with an antidepressant amount of a serotonin selective reuptake inhibitor (such as, but not limited to, sertraline, fluvoxamine, paroxetine, citalopram, fluoxetine and metabolites thereof) and an amount of a compound of Formula I sufficient to hasten the onset of antidepressant efficacy.
Also encompassed by the present invention are pharmaceutical compositions for treating or controlling disease states or conditions of the central nervous system comprising at least one compound of Formula I, mixtures thereof, and or pharmaceutical salts thereof, and a pharmaceutically acceptable carrier therefore. Such compositions are prepared in accordance with acceptable pharmaceutical procedures, such as described in Remingtons Pharmaceutical Sciences, 17th edition, ed. Alfonoso R. Gennaro, Mack Publishing Company, Easton, Pa. (1985). Pharmaceutically acceptable carriers are those that are compatible with the other ingredients in the formulation and biologically acceptable.
Compounds of the present invention may further be provided in combination with an antidepressant amount of a serotonin selective reuptake inhibitor to increase the onset of antidepressant efficacy.
The compounds of this invention may be administered orally or parenterally, neat or in combination with conventional pharmaceutical carriers. Applicable solid carriers can include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents or an encapsulating material. In powders, the carrier is a finely divided solid which is in admixture with the finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain up to 99% of the active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins.
Liquid carriers may be used in preparing solutions, suspensions, emulsions, syrups and elixirs. The active ingredient of this invention can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fat. The liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral administration include water (particularly containing additives as above e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols e.g. glycols) and their derivatives, and oils (e.g. fractionated coconut oil and arachis oil). For parenteral administration the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration.
Liquid pharmaceutical compositions which are sterile solutions or suspensions can be utilized by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously. Oral administration may be either liquid or solid composition form.
Preferably the pharmaceutical composition is in unit dosage form, e.g. as tablets, capsules, powders, solutions, suspensions, emulsions, granules, or suppositories. In such form, the composition is sub-divided in unit dose containing appropriate quantities of the active ingredient; the unit dosage forms can be packaged compositions, for example packeted powders, vials, ampoules, prefilled syringes or sachets containing liquids. The unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form.
The amount provided to a patient will vary depending upon what is being administered, the purpose of the administration, such as prophylaxis or therapy, and the state of the patient, the manner of administration, and the like. In therapeutic applications, compounds of the present invention are provided to a patient already suffering from a disease in an amount sufficient to cure or at least partially ameliorate the symptoms of the disease and its complications. An amount adequate to accomplish this is defined as a “therapeutically effective amount.” The dosage to be used in the treatment of a specific case must be subjectively determined by the attending physician. The variables involved include the specific condition and the size, age and response pattern of the patient. Generally, a starting dose is about 10 mg per day with gradual increase in the daily dose to about 200 mg per day, to provide the desired dosage level in the human.
Provide, as used herein, means either directly administering a compound or composition of the present invention, or administering a prodrug, derivative or analog which will form an equivalent amount of the active compound or substance within the body.
The present invention includes prodrugs of compounds of Formula I. “Prodrug”, as used herein means a compound which is convertible in vivo by metabolic means (e.g. by hydrolysis) to a compound of Formula I. Various forms of prodrugs are known in the art, for example, as discussed in Bundgaard, (ed.), Design of Prodrugs, Elsevier (1985); Widder, et al. (ed.), Methods in Enzymology, vol. 4, Academic Press (1985); Krogsgaard-Larsen, et al., (ed). “Design and Application of Prodrugs, Textbook of Drug Design and Development, Chapter 5, 113-191 (1991), Bundgaard, et al., Journal of Drug Deliver Reviews, 8:1-38(1992), Bundgaard, J. of Pharmaceutical Sciences, 77:285 et seq. (1988); and Higuchi and Stella (eds.) Prodrugs as Novel Drug Delivery Systems, American Chemical Society (1975).
The following examples illustrate the production of representative compounds of this invention.
INTERMEDIATE 1
3-Allyloxy-4-methoxynitrobenzene
97.5 g (0.51 mole) of the sodium salt of 5-nitroguaiacol was dissolved in one liter of DMF and 1.5 equivalents of allyl bromide added. The reaction was heated to 65° C. for two hours, after which time much of the dark color had discharged and tic (1:1 CH 2 Cl 2 /hexane) indicated loss of starting material. The solvent was concentrated in vacuum and the residue washed with water. The product was isolated by filtration and dried in a vacuum. This gave 112 g of pale yellow solid. A sample recrystallized from methanol, gave m.p. 93-94° C.
INTERMEDIATE 2
2-Allyloxy-4-nitrophenol
To one liter of dimethyl sulfoxide was added 750 mL of 2 N aqueous sodium hydroxide and the mixture was heated to 65° C. The pale yellow solid 3-allyloxy-4-methoxynitrobenzene prepared above was added in portions over a 30 minute period and then the temperature was raised to 95° C. and maintained for 3 hours, after which time the starting material had been consumed. The mixture was allowed to cool and poured into a mixture of 1 L ice and 1 L 2 N HCl. 73 Grams of crude but homogeneous (by tic 1:1 CH 2 Cl 2 /hexane) desired product was isolated as a light brown solid by filtration. This material was subsequently dissolved in 1:1 hexane/methylene chloride and filtered through silica gel to give 68 g of pale yellow solid, which, when recrystallized from ethyl/acetate/hexane, gave m.p. 61-62° C. The aqueous mother liquors from the initial crystallization above were extracted with 2 L of ethyl acetate. This was dried over sodium sulfate, filtered and evaporated to a dark oil. Column chromatography on silica with 1:1 CH 2 Cl 2 /hexane gave an additional 12 g of the title compound as a yellow solid. Elution with 2% MeOH in CHCl 3 gave 12 g of a dark oil which slowly crystallized in vacuum. This proved to be the Claisen product, 3-allyl-4-nitrocatechol.
INTERMEDIATE 3
2-(2-Allyoxy-4-nitrophenoxymethyl)-oxirane
20 g (0.50 mole) of 60% NaH/mineral oil was placed in a two liter flask and washed with 500 mL of hexane. 1 L of DMF was added, followed by 77 g (0.40 mole) of the 2-allyloxy-4-nitrophenol prepared in the previous step. Addition of the phenol was performed in portions under argon. After stirring the mixture for 30 minutes at room temperature under argon, 108 g (0.48 moles) of (R)-glycidyl tosylate was added and the mixture heated at 70-75° C. under nitrogen overnight. Upon cooling, the DMF was removed in vacuum and replaced with one liter of methylene chloride. This was washed with 500 mL portions of 2 N HCl, saturated sodium bicarbonate and saturated brine and dried over sodium sulfate. The mixture was filtered, concentrated to an oil in vacuum and column chromatographed on silica gel using 1:1 hexane/methylene chloride as eluant. This gave 43 g of product contaminated with traces of the two starting materials, followed by 21 g of pure product as a pale yellow solid. The impure material was recrystallized from 1.2 L of 10% ethyl acetate/hexane to give 34 g of pure (homogeneous on silica gel tic with 1:1 hexane/methylene chloride) (R)-2-(2-allyloxy-4-nitrophenoxymethyl)-oxirane (m.p. 64° C.).
Elemental Analysis for: C 12 H 13 NO 5 Calc'd: C, 57.37; H, 5.21; N, 5.58. Found: C, 57.50; H, 5.21; N, 5.43.
INTERMEDIATE 4
(8-Allyl-7-nitro-2,3-dihydro-benzo(1,4)dioxin-2-yl)-methanol
(R)-2-(2-Allyloxy-4-nitrophenoxymethyl)-oxirane (20 g, 80 mmoles) prepared as above was heated at 155° C. in mesitylene for 24 hours under nitrogen. Filtration of the black solid which formed gave 1.5 g of very polar material. Evaporation of the solvent in vacuum followed by column chromatography on silica gel with methylene chloride as eluant gave 10 g of recovered starting material and 7.5 g of the desired rearranged (S)-(8-allyl-7-nitro-2,3-dihydro-benzo(1,4)dioxin-2-yl)-methanol, which slowly crystallized on standing in vacuum (m.p. 67° C.). The yield based on recovered starting material is 75%.
Elemental Analysis for: C 12 H 13 NO 5 Calc'd: C, 57.37; H, 5.21; N, 5.58. Found: C, 57.26; H, 5.20; N, 5.35.
INTERMEDIATE 5
Toluene-4-sulfonic acid 8-allyl-7-nitro-2,3-dihydro-benzo(1,4)dioxin-2-ylmethyl ester
9.55 g (38.0 mmole) of (S)-(8-allyl-7-nitro-2,3-dihydro-benzo(1,4)dioxin-2-yl)-methanol was dissolved in 465 mL of pyridine, 29.0 g (152 mmole) of p-toluenesulfonyl chloride was added and the mixture stirred at room temperature under nitrogen overnight. Water was then added to quench the excess tosyl chloride and the solvent was removed in vacuum and replaced with methylene chloride. This solution was washed with 2 N HCl, with saturated sodium bicarbonate, and with saturated brine, and dried over magnesium sulfate. Filtration, evaporation in vacuum and column chromatography on silica gel with 1:1 hexane/methylene chloride as eluant gave 12.6 g (92%) of toluene-4-sulfonic acid (R)-allyl-7-nitro-2,3-benzo(1,4)dioxin-2-ylmethyl ester, which slowly crystallized to a tan solid (m.p. 60-62° C.) upon standing.
Elemental Analysis for: C 19 H 19 NO 7 S Calc'd: C, 56.29; H, 4.72; N, 3.45. Found: C, 56.13; H, 4.58; N, 3.44.
INTERMEDIATE 6
{7-Nitro-8-[1-propenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate
To a solution of 10.0 g (24.0 mmole) of (R)-[8-allyl-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate in 700 mL of benzene was added 1.03 g of bis(acetonitrile)dichloropalladium (II) and the mixture was refluxed under nitrogen for 48 hours. The catalyst was then removed by filtration and the filtrate concentrated in vacuum to a brown oil. Column chromatography on silica gel with methylene chloride as eluant gave 7.2 g of the title compound as a mixture of E and Z isomers. A sample of {(2R)-7-nitro-8[(E)-1-propenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate was obtained as a yellow solid (m.p. 105-106° C.) by evaporation of a pure E isomer-containing fraction.
Elemental Analysis for: C 19 H 19 NO 7 S Calc'd: C, 56.29; H, 4.72; N, 3.45. Found: C, 56.12; H, 4.64; N, 3.39.
INTERMEDIATE 7
{7-Nitro-8-[3-oxo-1-propenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate
{(2R)-7-nitro-8-[1-propenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate (6.15 g, 15.2 mmole) was dissolved in 180 mL of dioxane. Selenium dioxide (4.20 g, 37.9 mmole) was then added, followed by 0.70 mL of water. The heterogeneous mixture was heated at reflux under nitrogen for 5 hours. Upon cooling, the reaction was filtered and concentrated in vacuum to yield a dark yellow solid. This was dissolved in minimal ethyl acetate and column chromatographed on silica gel using 30% ethyl acetate in hexane as eluant to give 5.75 g of the (R)-enantiomer of the title compound as a light yellow solid (m.p. 138-140° C.).
Elemental Analysis for: C 19 H 17 NO 8 S Calc'd: C, 54.41; H, 4.09; N, 3.34. Found: C, 54.10; H, 3.85; N, 3.31.
INTERMEDIATE 8
2,3-Dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate
To a solution of {(2R)-7-nitro-8-[3-oxo-1-propenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate (3.50 g, 8.35 mmole) in 200 mL of acetic acid/ethanol (1:1) was added 2.35 g (42.1 mmole) of iron powder and the mixture was heated at reflux under nitrogen for 8 hours. After the reaction was complete, 150 mL of water was added and the mixture filtered through a pad of celite. The filtrate was neutralized with saturated sodium bicarbonate and extracted with ethyl acetate. The extract was dried over magnesium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel using a gradient elution commencing with 20% ethyl acetate/hexane and ending with 70% ethyl acetate/hexane to give 1.85 g of the (R)-enantiomer of the title compound as a yellow oil. 1 H-NMR (CDCl 3 ): doublet 8.8 δ (1 H); doublet 8.2 δ (1 H); doublet 7.8 δ (2 H); doublet 7.6 δ (1 H); multiplet 7.35 δ (1 H); multiplet 7.25 δ (3 H); multiplet 4.6 δ (1 H); multiplet 4.3-4.4 δ (3 H); multiplet 4.2 δ (1 H); singlet 2.4 δ (3 H).
EXAMPLE 1
8-[2,3-Dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
(2R)-2,3-Dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.41 g, 1.1 mmole) and 1-phenyl-1,3,6-triazaspiro[4.5]decan-4-one (0.75 g, 3.24 mmole) were combined in 30 mL of DMSO and heated at 80° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL each of ethyl acetate and saturated sodium bicarbonate solution. The organic phase was removed, washed with saturated brine, dried over magnesium sulfate and concentrated to a brown oil in vacuum. This was column chromatographed on silica gel using a gradient elution commencing with methylene chloride and ending with 3% methanol in methylene chloride to elute the product, 0.30 g of a reddish oil. The oil was recrystallized from ethanol with the addition of 0.12 g of fumaric acid to give 0.22 g of the (S)-enantiomer of the title compound as a yellow solid difumarate, m.p. 170° C.
Elemental Analysis for: C 25 H 26 N 4 O 3 .2 C 4 H 4 O 4 Calc'd: C, 59.81; H, 5.17; N, 8.45. Found: C, 59.88; H, 5.44; N, 8.38.
INTERMEDIATE 9
(8-Formyl-7- nitro-2,3-dihydro-1,4-benzodioxin-2-yl)methyl 4-methylbenzenesulfonate
{(2R)-7-Nitro-8-[1-propenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate (10.5 g, 25.9 mmole) dissolved in 400 mL of methylene chloride was treated with excess ozone at −78° C. Diisopropylethylamine (11.5 mL, 66.0 mmole) was then added dropwise over 30 minutes and the mixture allowed to come to room temperature and stir overnight under a nitrogen atmosphere. The mixture was then diluted to 600 mL with methylene chloride, washed three times with 100 mL portions of 2N HCl (aq), twice with 200 mL portions of saturated aqueous sodium bicarbonate and with 200 mL of saturated brine. The solution was dried over magnesium sulfate, filtered and concentrated in vacuum to a crude brown oil, which was column chromatographed on silica gel with 10% hexane/methylene chloride to give 7.52 g of the (R)-enantiomer of the title compound as a yellow solid. 1 H-NMR (CDCl 3 ): doublet 7.8 δ (2 H); doublet 7.62 δ (1 H); doublet 7.4 δ (2 H); doublet 7.0 δ (1 H); multiplet 4.4-4.6 δ (2 H); multiplet 4.2 δ (3 H); singlet 2.4 δ (3 H).
INTERMEDIATE 10
{7-Nitro-8-[(E)-3-oxo-1-butenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate
To a solution of 3.00 g (7.37 mmole) of [(2R)-8-formyl-7- nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate in 250 mL of toluene was added 2.90 g (9.10 mmole) of 1-triphenylphosphoranylidene-2-propanone. The mixture was stirred at room temperature under nitrogen for 5 hours, during which time some product precipitated from solution. The solvent was removed in vacuum and the crude residue was column chromatographed on silica gel with methylene chloride as eluant to give 3.0 g of the (R)-enantiomer of the title compound as a yellow solid. 1 H-NMR (CDCl 3 ): doublet 7.8 δ (2 H); doublet 7.6 δ (1 H); doublet 7.5 δ (2 H); doublet 7.4 δ (2 H); doublet 6.95 δ (1 H); doublet 6.6 δ (1 H); multiplet 4.5 δ (1 H); doublet of doublets 4.0 δ (1 H); multiplet 4.2 δ (3 H); singlet 2.45 δ (3 H); singlet 2.4 δ (3 H).
INTERMEDIATE 11
(8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl)methyl 4-methylbenzenesulfonate
To a solution of {(2R)-7-nitro-8-[(E)-3-oxo-1-butenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate (3.40 g, 7.83 mmole) in 200 mL of acetic acid/ethanol (3:2) was added 2.25 g (40.2 mmole) of iron powder and the mixture was heated at reflux under nitrogen for 8 hours. After the reaction was complete, 150 mL of water was added and the mixture filtered through a pad of celite. The filtrate was neutralized with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The extract was dried over magnesium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel using a gradient elution commencing with 20% ethyl acetate/hexane and ending with 70% ethyl acetate/hexane to give 2.5 g of the (R)-enantiomer of the title compound as a yellow oil. 1 H-NMR (CDCl 3 ): doublet 8.1 δ (1 H); doublet 7.6 δ (2 H); doublet 7.45 δ (1 H); multiplet 7.2 δ (4 H); multiplet 4.6 δ (1 H); multiplet 4.3 δ (3 H); multiplet 4.1 δ (1 H); singlet 2.5 δ (3H); singlet 2.4 δ (3 H).
EXAMPLE 2
8-{[8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.75 g, 2.0 mmole) and 1-phenyl-1,3,6-triazaspiro[4.5]decan-4-one (0.92 g, 4.0 mmole) were combined in 10 mL of DMSO and heated at 80° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL of ethyl acetate and 250 mL of saturated sodium bicarbonate solution. The organic phase was removed, washed with 250 mL of water, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel using 1% methanol in chloroform as eluant to give 0.29 g of a yellow oil. The oil was recrystallized from ethanol with the addition of one equivalent of fumaric acid to give 0.21 g of the (S)-enantiomer of the title compound as a gray solid hemifumarate, hydrate, m.p. 199-201° C.
Elemental Analysis for: C 26 H 28 N 4 O 3 .0.5 C 4 H 4 O 4 .H 2 O Calc'd: C, 64.60; H, 6.20; N, 10.76. Found: C, 64.51; H, 5.89; N, 10.66.
EXAMPLE 3
1-(1-{[8-Methyl-2,3-dihydro[1,4]di xino[2,3-f]quin lin-2-yl]methyl}piperidin-4-yl)-1,3-dihydro-2H-benzimidazol-2-one
(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.75 g, 2.0 mmole) and 4-(2-keto-1-benzimidazolinyl)-piperidine (1.0 g, 4.6 mmole) were combined in 10 mL of DMSO and heated at 90-100° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL of ethyl acetate and 400 mL of saturated sodium bicarbonate solution. The organic phase was removed, washed with 400 mL of water, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel using 1% methanol in chloroform as eluant to give 0.59 g of a yellow oil. The oil was recrystallized from isopropanol with the addition of one equivalent of fumaric acid to give 0.40 g of the (S)-enantiomer of the title compound as a pale yellow solid fumarate, sesquihydrate, m.p. 194-196° C.
Elemental Analysis for: C 25 H 26 N 4 O 3 .C 4 H 4 O 4 .1.5 H 2 O Calc'd: C, 60.72; H, 5.80; N, 9.77. Found: C, 60.90; H, 5.96; N, 9.63.
EXAMPLE 4
8-Methyl -2-(piperidin-1-ylmethyl)-2,3-dihydro[1,4]dioxino[2,3-f]quinoline
(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.75 g, 2.0 mmole) was dissolved in 10 mL of piperidine and heated at reflux under nitrogen for 6 hours. After cooling to room temperature, the mixture was concentrated to an oil in vacuum. The residue was column chromatographed on silica gel using 1% methanol in chloroform as eluant to give 0.41 g of a yellow oil. The oil was recrystallized from isopropanol with the addition of 1 mL of 4 N isopropanolic HCl to give 0.35 g of the (S)-enantiomer of the title compound as a yellow solid dihydrochloride, hemihydrate, m.p. 278-280° C.
Elemental Analysis for: C 18 H 22 N 2 O 2 .2HCl.0.5 H 2 O Calc'd: C, 56.85; H, 6.83; N, 7.37. Found: C, 56.74; H, 6.65; N, 7.07.
EXAMPLE 5
(4-Fluorophenyl)(1-{[8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-4-piperidinyl)methanone
(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.75 g, 2.0 mmole) and 4-(4-fluorobenzoyl)-piperidine (1.0 g, 4.8 mmole) were combined in 10 mL of DMSO and heated at 80-90° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL of ethyl acetate and 400 mL of saturated sodium bicarbonate solution. The organic phase was removed, washed with 400 mL of water, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel using 0.5% methanol in chloroform as eluant to give 0.17 g of a yellow oil. The oil was recrystallized from ethanol with the addition of one equivalent of fumaric acid to give 0.18 g of the (S)-enantiomer of the title compound as an off-white solid fumarate, one-quarter hydrate, m.p. 206-207° C.
Elemental Analysis for: C 25 H 25 FN 2 O 3 .C 4 H 4 O 4 .0.25 H 2 O Calc'd: C, 64.38; H, 5.50; N, 5.18. Found: C, 64.67; H, 5.55; N, 4.97.
EXAMPLE 6
1-{[8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-4-[3-(trifluoromethyl)phenyl]-4-piperidinol
(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.75 g, 2.0 mmole) and 4-[(3-trifluoromethyl)phenyl]-4-hydroxypiperidine (1.0 g, 4.1 mmole) were combined in 10 mL of DMSO and heated at 80° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL of ethyl acetate and 300 mL of saturated sodium bicarbonate solution. The organic phase was removed, washed with 300 mL of water, dried over magnesium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel using 1% methanol in methylene chloride as eluant to give 0.57 g of a yellow oil. The oil was recrystallized from ethanol with the addition of one equivalent of fumaric acid to give 0.30 g of the (S)-enantiomer of the title compound as a pale yellow solid fumarate, three-quarter hydrate, m.p. 133-135° C.
Elemental Analysis for: C 25 H 25 F 3 N 2 O 3 .C 4 H 4 O 4 .0.75 H 2 O Calc'd: C, 59.23; H, 5.23; N, 4.76. Found: C, 59.12; H, 5.41; N, 4.47.
EXAMPLE 7
1-{[8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-4-phenyl-4-piperidinecarbonitrile
(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.75 g, 2.0 mmole) and 4-phenyl-4-cyanopiperidine (1.0 g, 5.4 mmole) were combined in 10 mL of DMSO and heated at 80-90° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL of ethyl acetate and 300 mL of saturated sodium bicarbonate solution. The organic phase was removed, washed with 300 mL of water, dried over magnesium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel using 1% methanol in methylene chloride as eluant to give 250 mg of a yellow oil. The oil was recrystallized from ethanol with the addition of one equivalent of fumaric acid to give 0.19 g of the (S)-enantiomer of the title compound, m.p. 185-7° C.
Elemental Analysis for: C 25 H 25 N 3 O 2 .C 4 H 4 O 4 Calc'd: C, 67.56; H, 5.67; N, 8.15. Found: C, 67.24; H, 5.71; N, 8.00.
EXAMPLE 8
8-Methyl-2-{[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]methyl}-2,3-dihydro[1,4]dioxino[2,3-f]quinoline
(2R)-8-Methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.75 g, 2.0 mmole) and 4-phenyl-1,2,3,6-tetrahydropyridine (1.0 g, 6.3 mmole) were combined in 10 mL of DMSO and heated at 80-90° C. under nitrogen for 6 hours. After cooling to room temperature, the mixture was partitioned between 400 mL of ethyl acetate and 400 mL of saturated sodium bicarbonate solution. The organic phase was removed, washed with 400 mL of water, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel using 0.5% methanol in methylene chloride as eluant to give 0.34 g of a yellow oil. The oil was recrystallized from ethanol with the addition of 0.15 g of fumaric acid to give 0.12 g of the (S)-enantiomer of the title compound as a white solid sesquifumarate, one-quarter hydrate, m.p. 185-188° C.
Elemental Analysis for: C 24 H 24 N 2 O 2 .1.5 C 4 H 4 O 4 .0.25 H 2 O Calc'd: C, 65.39; H, 5.58; N, 5.08. Found: C, 65.26; H, 5.37; N, 5.08.
INTERMEDIATE 12
{7-Nitro-8-[(E)-3-oxo-1-pentenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate
To a solution of 5.00 g (12.2 mmole) of [(2R)-8-formyl-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate in 200 mL of toluene was added 5.10 g (15.3 mmole) of 1-triphenylphosphoranylidene-2-butanone. The mixture was stirred at room temperature under nitrogen for 5 hours, after which time the solvent was removed in vacuum and the crude residue was column chromatographed on silica gel with methylene chloride as eluant to give 5.0 g of the (R)-enantiomer of the title compound as a yellow solid (m.p. 114° C.).
Elemental Analysis for: C 17 H 15 NO 8 S Calc'd: C, 56.37; H, 4.73; N, 3.13. Found: C, 56.81; H, 4.60; N, 3.01.
INTERMEDIATE 13
(8-Ethyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl)methyl 4-methylbenzenesulfonate
To a solution of {(2R)-7-nitro-8-[(E)-3-oxo-1-pentenyl]-2,3-dihydro-1,4-benzo-dioxin-2-yl}methyl 4-methylbenzenesulfonate (1.57 g, 3.50 mmole) in 100 mL of acetic acid/ethanol (1:1) was added 1.00 g (17.9 mmole) of iron powder and the mixture was heated at reflux under nitrogen for 8 hours. After the reaction was complete, 150 mL of water was added and the mixture filtered through a pad of celite. The filtrate was neutralized with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The extract was dried over magnesium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel using a gradient elution commencing with 20% ethyl acetate/hexane and ending with 70% ethyl acetate/hexane to give 0.94 g of the (R)-enantiomer of the title compound as a yellow oil. 1 H-NMR (CDCl 3 ): doublet 8.2 δ (1 H); doublet 7.8 δ (2 H); doublet 7.55 δ (1 H); 7.2-7.3 δ (4 H); multiplet 4.6 δ (1 H); multiplet 4.2-4.4 δ (3 H); multiplet 4.1 δ (1 H); quartet 3.0 δ (2 H); singlet 2.4 δ (3 H); triplet 1.4 δ (3 H).
EXAMPLE 9
8-{[8-Ethyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
(2R)-8-Ethyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-ylmethyl 4-methylbenzenesulfonate (0.45 g, 1.1 mmole) and 1-phenyl-1,3,6-triazaspiro[4.5]decan-4-one (0.78 g, 3.4 mmole) were combined in 30 mL of DMSO and heated at 80° C. under nitrogen for 3 hours. After cooling to room temperature, the mixture was partitioned between 400 mL each of ethyl acetate and saturated sodium bicarbonate solution. The organic phase was removed, washed with saturated brine, dried over magnesium sulfate and concentrated to a brown oil in vacuum. This was column chromatographed on silica gel with 3% methanol in methylene chloride as eluant to give 0.31 g of a yellow oil. The oil was recrystallized from ethanol with the addition of 0.094 g of fumaric acid to give 0.10 g of the (S)-enantiomer of the title compound as a yellow solid fumarate, hemihydrate, m.p. 207-209° C.
Elemental Analysis for: C 27 H 30 N 4 O 3 .C 4 H 4 O 4 .0.5 H 2 O Calc'd: C, 63.80; H, 6.04; N, 9.60. Found: C, 63.82; H, 5.81; N, 9.36.
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Compounds of the formula
useful for the treatment of disorders, such as anxiety, aggression and stress, and for the control of various physiological phenomena, such as appetite, thermoregulation, sleep and sexual behavior.
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FIELD OF THE INVENTION
The invention relates to lithotripsy apparatus comprising; an ultrasonic shock wave generator provided with a coupling cushion which is adaptable to the body of a patient to be treated by means of the shock wave generator, and which receives water as an acoustic coupling medium between the shock wave generator and the body of the patient; a device for controlling the pressure of the coupling medium in the coupling cushion; and a device for removing the gas from the coupling medium. Such apparatus are used for the destruction of concretions in a patient's body.
Water is commonly used as a coupling medium for introducing ultrasonic shock waves into the regions of a patient's body that are to be treated, since water has an acoustic impedance which is similar to that of the body tissue of a living being. The water should, however, be substantially free of gas and any gas produced during the shock wave therapy should be removed from the coupling medium. A coupling medium containing gas cannot be used efficiently in carrying out shock wave therapy because the acoustic impedance of said medium is thereby altered. Also, care must be taken to maintain constant, tight contact between patient's body and the coupling medium in such a way that the shock waves can always be precisely focused onto the concretion to be destroyed in the body.
BACKGROUND OF THE INVENTION
There is disclosed in DE-A-38 11 316, lithotripsy apparatus in which a sealed coupling cushion is filled with water as the coupling medium and is placed on a patient's body so that the shock wave energy can be transmitted through the medium of the water to a concretion to be disintegrated. A gas removal device ensures that the water in the water cushion is gas free and a controlled pressure regulating device ensures that the pressure in the water cushion is at an optimum value. The quality of the water used in the cushion can, however, deteriorate, for example algae may produce slime which reduces the efficiency of the shock wave transmission and thereby impairs the success of the treatment. A defect in the means for circulating the water for the water cushion, may allow water to escape into the open, so as to endanger the sterility of the room in which the patient is being treated. If an open coupling cushion is used the water may escape into the treatment room so that the treatment space or the treatment room must be cleaned and disinfected.
According to the disclosure of DE-A-35 44 628 and DE-A-32 20 751, the ultrasonic shock waves are coupled-in by way of a coupling bag or coupling cushion, filled with gas-free water, which is adapted to the body of the patient with the open part of the coupling bag or cushion contacting the patient or with a membrane shielding the patient. Such an enclosed water circuit has the disadvantage that the growth of algae or the like can cause the coupling medium rapidly to become fouled with slime. DE-A-35 44 628 and DE-A-32 20 751 do not, however, disclose how the water coupling medium is treated in order to prevent slime formation, and in the matter of degasification mention only that air removal tubes can be introduced in the region of the shock wave generator and the sealing edge.
With lithotripsy apparatus of the type under discussion, there is also difficulty in maintaining the contact pressure of the coupling cushion against the body of the patient at an optimum pressure when the weight of the patient's body acts against the coupling cushion. Since during positioning of the patient on the coupling cushion, the coupling medium exerts a counter pressure towards the patient, it may not be possible to bring a stone to be disintegrated into the focus of the shock waves.
EP-A-0 265 741 discloses apparatus for destroying concretions in the body of a living being. The apparatus comprises disintegrating shock wave generators, filled with a liquid coupling medium, and a liquid circuit with a container and circulating pump. The circulation of the liquid is in an operating circuit and a filling and gas removal circuit. In the filling and gas removal circuit, gas is removed from the liquid supplied with the aid of a vacuum pump and is subsequently fed from a storage container to the shock wave generator or generators.
This apparatus has the disadvantage that the use of containers for preparing the liquid and for removing gas from the liquid, entails that the apparatus is uneconomical of space. Further, since the coupling medium becomes fouled with slime it must be constantly replaced after only short periods of time.
Apart from the disadvantages just mentioned, particular care must be taken to ensure that no germs are transferred from patient to patient by way of the coupling medium, especially if the coupling cushion is exposed towards the patient.
SUMMARY OF THE INVENTION
The invention is intended to provide lithotripsy apparatus that is economical of space and is of simple construction, the quality of the coupling medium being safeguarded, and water from a mains drinking water supply being usable as the coupling medium.
According to the present invention lithotripsy apparatus comprises; a shock wave generator provided with a coupling cushion, adaptable to the body of a patient to be treated and which receives water as an acoustic coupling medium between the shock wave generator and the body of the patient; a device for controlling the pressure of the water in the coupling cushion; a device for removing the gas from the coupling medium; and before the degasifying device, a disinfecting device in which are a storage container for receiving a disinfectant, a control circuit for the storage container and a metering device connected to the storage container for supplying disinfectant to the coupling medium.
The quality of the coupling medium which may be taken directly from a main drinking water supply, remains unimpaired or may even be improved, as the coupling medium is disinfected so that germs cannot multiply, or algae grow in the coupling medium. The coupling medium is accordingly prevented from becoming fouled by slime, thereby ensuring that the quality of transmission of the ultrasonic shock wave energy to the body of the patient is guaranteed and that said energy has a high degree of effectiveness. Similarly, when an open coupling cushion is used or if there is a defect in the lithotripsy apparatus, the germ-free atmosphere of the treatment room or treatment space is not impaired, so that it does not need to be disinfected. The provision of the disinfecting device adds little to the space needed to accommodate the lithotripsy apparatus.
The metering device may comprise a metering pump, a nonreturn valve following the pump, and a magnetic valve for introducing the metered disinfectant into the coupling medium.
The coupling cushion may communicate with a pressure equalising vessel defining a space a part of which is filled with gas and which is separated by a flexible membrane from the remainder of the space which can be filled with coupling medium.
When smaller quantities of disinfectant are used the metering pump of the disinfecting device should be intermittently operated. Furthermore, in order to achieve a long period of usefulness of the prepared coupling medium, a pipe may be provided which links a main circuit for filling and emptying the coupling cushion to the disinfecting device.
BRIEF DESCRIPTION OF THE DRAWING
The single FIGURE is a block schematic diagram of a lithotripsy apparatus.
DETAILED DESCRIPTION OF THE INVENTION
A lithotripsy apparatus according to an embodiment of the invention comprises a disinfecting device 1, a water degasifying device 2 operating according to the vacuum gas removal principle, a main circuit 3 for filling and emptying a water containing, closed coupling cushion 34, of a shock wave generator 4, and a central electronic control unit 5 for controlling the devices 1 and 2 and the main circuit 3.
The disinfecting device 1 serves to prevent the growth and proliferation of bacteria, viruses, fungi, algae and the like, thereby to prevent the water in the coupling cushion 34 from becoming fouled with slime and to prevent possible contamination of a patient under the treatment. The device 1 is preferably connected to the main drinking water supply via a water tap 6. The connection of the device 1 to the water supply is made by way of a first magnetic valve 7 which is connected in series with a water flow regulator 8, a pipe divider 9, a flow volume measuring device 10 and a second magnetic valve 11. A metering device 12 is connected to the pipe connecting the magnetic valve 11 to the flow volume measuring device 10. The metering device 12, as seen from a disinfectant injection point 13, comprises, connected in series, a third magnetic valve 14, a nonreturn valve 15, a metering pump 16 and a disinfectant storage container 17 provided with a suction pipe 18 and disinfectant level sensors 19. The disinfecting device 1 is controlled by means of an electronic control circuit 20.
The disinfecting device 1 is connected by way of a feed pipe 21, which is, in turn, connected to the outlet of the second magnetic valve 11, to the water degasifying device 2. The pipe 21 is connected to the device 2 by way of a magnetic valve 22, for supplying water to an injection nozzle 23 terminating within a gas removal container 24 having water level sensors 25. A vacuum pump 26 is connected to the container 24 by way of a magnetic valve 27 and a water-impermeable filter 28 communicating with the interior of the gas removal container 24. The vacuum pump 26 is connected in series with a filter 29 for releasing suctioned-off gas into the atmosphere. The outlet of the container 24 is connected to a magnetic valve 30 which is, in turn, connected in series with a pump 31, the use of which is described below, with regard to another embodiment of the water degasifying device 2. The degasifying device 2 is controlled by means of a control circuit 32.
The outlet side of the pump 31 is connected by way of a feed pipe 33, to the main circuit 3 for filling and emptying the coupling cushion 34 of the shock wave generator 4. The pipe 33 is connected to a magnetic valve 35, which is in turn connected to the inlet side of a circulating pump 36 the outlet side of which is connected to a pressure equalising container 37. The container 37 is provided with a laterally inserted balloon 38 which is supplied with compressed air by means of an air pump 39 and is emptied with the aid of a magnetic valve 40. A limit indicator 41 is arranged to monitor the pressure relationships in the balloon 38. Instead of the balloon 38, a membrane 38a may be used for dividing the container 37 so as to provide a sub-chamber, which can be filled with compressed air. The pressure equalising chamber 37 may be provided with a heater 42. The water containing part of the equalising container 37 is connected to the water chamber of the coupling cushion 34 by way of a connecting pipe 43 of relatively large cross-section. At its lowest point, the pipe 43 is provided with a magnetic valve 44 for use in emptying the system by means of a suction pump 45. The pressure in the coupling cushion 34 is controlled by means of a pressure regulator 46.
The water level in the water chamber of the coupling cushion 34 is monitored by means of a pressure gauge 47. There leads from the region of the highest point of the coupling cushion 34, a suction pipe 48 connected to a container 49. The container 49 is arranged to be ventilated by means of a valve 50 regulated by means of a control device 51. The water level in the container 49 is controlled by means of level sensors 52. Within the container 49 is a heater 53 for heating the contents thereof. The base of the container 49 is connected by way of a magnetic valve 54 to the pipe connecting the magnetic valve 35 to the circulating pump 36. Between the valve 54 and said connecting pipe there is connected a pipe 55 which is in turn, connected to said third magnetic valve 14 of the disinfecting device 1.
The apparatus described above operates as follows:
The disinfecting device 1 connected to the main drinking water supply is filled by opening the magnetic valves 7 and 11, whereby a substantially constant stream of water is caused to flow through the flow regulator 8, the pipe divider 9 and the flow volume measuring device 10, and by way of the magnetic valve 11, into the feed pipe 21 of the water degasifying device 2. Disinfectant from the storage container 17 is thus added to the water by the metering pump 16 at the disinfectant injection point 13. The metering pump 16 is controlled by the flow volume measuring device 10 and the control circuit 20, so as to ensure that the disinfectant is always metered in accordance with the actual volume of water flowing, independently of the pressure of the mains supply. Where there is a very strong concentration of the disinfectant in the storage container 17, the metering pump 16 is only controlled intermittently by the volume measuring device 10. During the intervals of such control the nonreturn valve 15 ensures that the supply of disinfectant from the storage container 17 is blocked.
The disinfectant level sensor 19 monitors the disinfectant level in the storage container 17 and passes information as to said level to the control circuit 20. The circuit 20 ensures that when the storage container 17 is empty, the metering pump 16 cannot be put into operation by the flow volume measuring device 10, and also ensures that the magnetic valves 7 and 11 are closed. The circuit 20 further ensures that at the start of the operation when the storage container 17 is already empty, the magnetic valves 7 and 11 are not opened in the first place. The control circuit 20 reports the empty condition of the container 17 to the central control unit 5 which signals such condition by activating an optical and/or acoustic indicator 56 arranged for example on the operating panel of the lithotripsy apparatus.
The magnetic valve 11 also ensures that any vacuum there may be in the pipe 21 does not cause the storage container 17 to be sucked dry by the next system. If the pressure on the inlet side of the valve 11 falls below a predetermined minimum level, the pipe divider 9 isolates the disinfecting device 1 from the drinking water supply by means of drain 9a in order to prevent disinfectant from getting into the drinking water.
The water is supplied to the water degasifying device 2 by way of the pipe 21. The gas removal container 24 is evacuated by the vacuum pump 26 to a desired pressure which is dependent upon the water temperature. Said desired pressure may be adjusted with the aid of pressure pick-up means or the pumping time of the pump 26 may be selected in accordance with the output of the vacuum pump 26. When said desired pressure has been reached, the magnetic valve 22 is opened, to allow the water to pass from the disinfecting device 1. The water under pressure in the device 1, assisted by the vacuum in the gas removal container 24, is thus forced and sucked through the injection nozzle 23 into the container 24. As the water droplets enter the container 24, gas bubbles are separated from the water by cavitation. The gas so produced is then sucked by the pump 26 through the water impermeable filter 28 and the valve 27 and is expelled into the atmosphere by way of the filter 29. When the water level in the gas removal container 24 has reached the required value as measured by the water level sensors 25, the control circuit 32 closes the magnetic valve 22 so as to terminate the filling of the container 24.
The vacuum in the gas removal container 24 is maintained for some time after said termination of the filling of the container 24, so that gas bubbles carried along by the water as a result of the high injection rate thereof, so as to be mixed in with the water, rise to the surface of the water and are suctioned off and expelled into the atmosphere in the manner described above. The fully degasified water now contained in the gas removal container 24, after the ventilation thereof by way of the valve 27 and the water impermeable filter 28, is then supplied by way of the magnetic valve 30 to the main circuit 3 for filling the coupling cushion 34 of the shock wave generator 4. Further water can subsequently be supplied to the main circuit 3 in the manner described above. Such degasifying and filling cycle is continued until the cushion 34 has been filled with the necessary volume of degasified and disinfected water.
According to said other embodiment of the degasifying device 2, the vacuum pump 26, which is expensive, is omitted and the pump 31, which is for example a gear pump, which can produce sufficient suction on its suction side, is provided as aforesaid between the magnetic valve 30 of the degasifying device 2 and the feed pipe 33 to the coupling cushion 34. In this embodiment the gas removal container 24, which has not been evacuated through the magnetic valve 22 operated by the control circuit 32, is first filled with a given volume of water from the disinfecting device 1. The water level in the container 24 is as in the first embodiment of the device 2 controlled by the control circuit 32 by way of the water level sensors 25 and the magnetic valve 22. When the selected water level has been reached, the control circuit 32 shuts the magnetic valve 22, opens the magnetic valve 30 and activates the pump 31. The consequent suctioning off a proportion of the water in the gas removal container 24 causes a vacuum to be formed in the space between magnetic valve 22 and the surface of the water in the container 24. When the said desired pressure in the gas removal container 24 has been reached, as determined by the water level sensors 25, and has been reported to the control circuit 32, the control circuit 32 causes the magnetic valve 22 to open. The water then entering by way of the injection nozzle 23 is degasified according to the principle described above and the gas bubbles can if required be released to the atmosphere through vent 27a by way of the water-impermeable filter 28 and the magnetic valve 27. Thus, in contrast with the degasifying process using the vacuum pump 26 according to the first embodiment of the device 2, a continuous gas removal and filling cycle can be achieved.
The water degasified in the manner just described is degasified to almost the same extent as in said first embodiment, despite the fact that it consists of a mixture of the degasified water and the gasified water initially introduced into the container 24. Total degasification is achieved, because the volume of gasified water in relation to the volume of water that is required for filling the coupling cushion 34, and, therefore, in relation to the volume of degasified water, is very small.
The degasified water is supplied to the main circuit 3 by way of the pipe 33. When the magnetic valve 30 is open and the pump 31 is switched on, the water pumped to the main circuit 3 by way of the pipe 33, after the valve 35 has been opened and the circulating pump 36 has been switched on, is pumped by the pump 36 through the pressure equalising container 37 into the coupling cushion 34 until the latter as been completely filled with degasified water. During this filling process, the free space for the through-flowing water in the pressure equalising container 37 is kept to a minimum. To this end, the balloon 38 is inflated by the pump 39 until it takes up almost the entire volume of the container 37, since it is the cushion 34 that is to be filled with water and not the equalising container 37. The coupling cushion 34 is accordingly disposed to allow a maximum of water to be taken up.
Before the cushion 34 is filled with water, the air in the cushion 34 and in its connecting pipe 43, is fed to the container 49 via the suction pipe 48. Since the pipe 43 is of large cross-section control variations resulting from the detection of delayed pressure variations can be kept to a minimum. The container 49 can be ventilated through the valve 50 which is operated by the control device 51. The valve 50 remains open until the container 49 and thus also the coupling cushion 34 are completely filled with water. The extent to which the container 49 has been filled is determined with the aid of the level sensors 52 and the valve 50 is operated by the control device 51.
The extent to which the coupling cushion 34 has been filled is monitored by the pressure gauge 47 which upon detecting a predetermined pressure, signals the central control unit 5 which, in turn, emits appropriate control signals which put the disinfecting device 1 and the degasifying device 2 out of operation, shut the magnetic valve 35 and open the magnetic valve 54. The circulating pump 36 now circulates the water in a closed circuit. The heater 42 heats the water for example to body temperature. The heater 42 is controlled by the control device 51, since the heater 42 must only be operated when it is immersed. Since the heater 42 is in the vessel 37, and is not in the container 49, the container 49 can be very small. The control device 51 and the level sensors 52 may be omitted and the valve 50 may, for example, be replaced by a simple float switch.
The water displaced by a patient when being positioned for treatment is taken up by the equalising container 37 and the pressure in the system is maintained constant by the pressure regulator 46 with the aid of the magnetic valve 40 of the air pump 39 and the limit indicator 41. The limit indicator 41 ensures that the balloon 38 is not overinflated so as to cause itself and the pressure equalising container 37 to be damaged or to burst.
When the shock wave generator 4 is being used, the prepared water is circulated by the circulating pump 36 in a closed circuit after the magnetic valve 35 has been closed, the circulating water being kept at the desired temperature by the heater 42 or 53.
In order to keep the prepared water in the lithotripsy apparatus as long as possible, the central control unit 5 controls, if necessary, the disinfecting device 1 in such a way that disinfectant reaches the disinfectant injection point 13 of the closed water circuit by way of the magnetic valve 14 and the pipe 55.
Any gas bubbles produced during the operation of the lithotripsy apparatus, for example, as a result of cavitation during shock wave therapy or as a result of gas given off by the disinfection agent, are removed from the coupling cushion 34 through the suction tube 48 and by way of the container 49 and the valve 50 and the gas is released into the atmosphere in the same way as the air is removed during the filling process.
The coupling cushion 34 may be emptied at anytime by way of the magnetic valve 44 and the suction pump 45 and emptying of the apparatus can likewise be effected by way of the central control unit 5. The other containers may be emptied by equivalent means.
If large volumes of air and/or water are to be suctioned off from the coupling cushion 34, as may be necessary when changing its membrane, the main circuit 3 may be modified by omitting the container 49, the device 51, the sensors 52, and the heater 53. In this case the valve 50 is replaced by a valve (not shown) having an inlet and two outlets and being connected by way of a pipe 57 (shown in broken lines) to the magnetic valve 22 of the degasifying device 2. Suction then takes place by way of the pipe 48 directly to said replacement valve and further by way of the pipe 57 to the valve 22. In this case the said replacement valve and the valve 54 are connected to each other by one pipe only.
Instead of the closed coupling cushion 34 an open coupling cushion (not shown)may be used.
By appropriate choice of disinfectant, for example, a disinfectant of which less than 0.5 ppm needs to be added to the water, the storage container 17 of the disinfecting device 1 can be very small whilst still being capable of containing enough disinfectant to last throughout a whole service interval.
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There is disclosed lithotripsy apparatus comprising an ultrasonic shock wave generator having a coupling cushion which is adaptable to the body of a patient to be treated by means of the shock wave generator and which can be filled with water as the acoustic coupling medium between the body of the patient and the shock wave generator. Devices are provided for degasifying the water and for continuously disinfecting it for the prevention of slime formation therein, for example the growth of algae.
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BACKGROUND OF THE INVENTION
[0001] The invention relates to lifting fixtures used to precisely control the attitude of loads being handled by overhead cranes.
[0002] In many aerospace and related industries, the loads being lifted by cranes are expensive, delicate, and require precise manipulation at many stages in the manufacturing process. This problem has been solved in the past by the design and construction of a large array of special fixtures or adapters each of which permit a single type load to be lifted. It is desirable from a cost and schedule standpoint to have a more universal solution. Specifically, it is desirable to have a single device that adapts itself to a larger number of load types.
[0003] In lifting any load with an overhead crane, stability requires that the center of gravity of the load has to be directly below the hook. An automatic system must move the load in two dimensions relative to the hook so that a stable lift is possible. However, an automated system, especially one that is lifting heavy items, could easily injure personnel and damage equipment if a malfunction occurred. Of particular concern would be a “runaway” drive element, which would swing the load. Moreover, an ease of use is important to efficient manufacturing operations and computerized control is the current state of the art way to achieve such ease of use.
[0004] The present invention increases the reliability of a self-adjusting load bar by means of a safety architecture that facilitates preventing a “runaway” malfunction without compromising the ease of use.
BRIEF DESCRIPTION OF THE INVENTION
[0005] In one aspect, a method is provided for assembling a load bar assembly. The method includes providing a first linear stage having a first alignment mechanism that is configured to move the load bar assembly in a first direction. A second linear stage is provided that includes a second alignment mechanism that is configured to move the load bar in a second direction that is different from the first direction. The first alignment mechanism is positioned with respect to the second alignment mechanism such that the first alignment mechanism and the second alignment mechanism are prevented from being back-driven. The first alignment mechanism and the second alignment mechanism are configured to lock if one of the first alignment mechanism and the second alignment mechanism fails.
[0006] In another aspect, a frame is provided for use with a load bar assembly. The frame includes a first alignment mechanism that is configured to move the frame in a first direction, and a second alignment mechanism that is configured to move the frame in a second direction that is different from the first direction. The first alignment mechanism is positioned with respect to the second alignment mechanism such that the first alignment mechanism and the second alignment mechanism are prevented from being back-driven. The first alignment mechanism and the second alignment mechanism are configured to lock if one of the first alignment mechanism and the second alignment mechanism fails.
[0007] In a further aspect, a load bar assembly is provided that includes a first linear stage including a first alignment screw that is configured to move the load bar assembly in a first direction. A second linear stage is provided that includes a second alignment screw that is configured to move the load bar in a second direction that is different from the first direction. The first alignment screw is positioned with respect to the second alignment screw such that the first alignment screw and the second alignment screw are prevented from being back-driven. The first alignment screw and the second alignment screw are configured to lock if one of the first alignment screw and the second alignment screw fails.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 is a schematic of an exemplary self-adjusting load bar.
[0009] FIG. 2 is a block diagram of an under hook that may be used with the self-adjusting load-bar show in FIG. 1 .
[0010] FIG. 3 is a block diagram of a ground control that may be used with the self-adjusting load-bar show in FIG. 1 .
[0011] FIG. 4 is a view of a password screen that may be used with the self-adjusting load-bar show in FIG. 1 .
[0012] FIG. 5 is a view of a tilt screen that may be used with the self-adjusting load bar shown in FIG. 1 .
[0013] FIG. 6 is a view of a preset screen that may be used with the self-adjusting load bar shown in FIG. 1 .
DETAILED DESCRIPTION OF THE INVENTION
[0014] The load bar assembly described herein includes an X linear stage held by an overhead crane hook, and stacked on a Y direction linear stage that holds the load. Each linear stage contains dual-redundant motor drives with separate motors and controllers. Because the gear ratio of the linear screws is such that they cannot be back driven, the linear screws will lock mechanically if one of the drives fails. In addition, the screws will lock if the two drives are not synchronized. This prevents a motor/controller runaway from being able to move the device. Automatic leveling is achieved by the use of three redundant two-axis tilt sensors that provide input to motion control computers. Further, safety is enhanced by the inclusion of a deadman switch. Motor operation is not permitted unless this deadman switch is held closed by the operator.
[0015] FIG. 1 is a view of a self-adjusting load bar mechanism 100 . An X frame 101 connects to the hook of the overhead crane using a four-way sling with through eye bolts 104 . The X drive is operated by two motors 103 that each turn a ball bearing screw. When the motors are turned synchronously, a Y frame 102 is moved back and forth along rails. Similarly, the Y frame 102 is driven in the orthogonal direction by two Y motors. The load is attached by means of eye bolts 104 on the bottom of the assembly. In the exemplary embodiment, controls and battery power for the self-adjusting load bar mechanism are contained in an electronic enclosure 105 .
[0016] The sizing and strength of the mechanical components is important to the safety of load bar 100 . Accordingly, in the exemplary embodiment, a single linear X drive is configured to support the load completely in the event of a failure of another X drive. As such, even if one of the two drives fails in a “runaway” mode, the screw on the other side will restrain it. Synchronization of the two X servo systems must be achieved to allow the unit to operate in the X-direction.
[0017] The dual Y drive is mechanically designed to have the same safety factor. Accordingly, a single linear Y drive can hold an entire load. Further, synchronization of the two Y servo systems must be achieved to allow the unit to move in the Y-direction.
[0018] In the exemplary embodiment, the load bar controls include at least two motion controllers. Each controller includes an X and Y absolute position encoder, a two axis tilt sensor, a two channel DC switching amplifier, an X DC motor, and Y DC motor. The X and Y DC motors are capable of handling the full load. The controls also include an additional controller 205 that acts as a safety arbitrator and operates an E-stop. The additional motor includes an X and Y absolute position sensor and a two axis tilt sensor.
[0019] FIG. 2 is a block diagram of an under the hook control system. Control messages are received via an on-board radio 201 . These control messages are transmitted on a communications bus 202 that allows three on board controllers 203 , 204 , and 205 to communicate with each other and via radio to the ground control system (shown in FIG. 3 ). Functionality is divided between the controls components so that a “runaway” failure cannot occur on any single point of failure. Thus, if computer 203 or any of its collection of peripheral elements (dual amplifier 206 , motors 207 / 208 , encoders 216 , and/or tilt sensors 218 ) fail, only half of each stage will be impacted. With the other half working normally the system will mechanically lock in a fail-safe manner. By symmetry the same fail-safe operation is realized if computer 204 or any of its peripheral devices fail.
[0020] To further enhance safety, a third computer 205 is added. This computer has its own set of sensors to enable it to check the motion control computers. Computer 205 executes continuous safety checks and turns motion power off if a position, tilt, and/or communications discrepancy is detected. In addition, this computer operates red 221 and green 222 lights used by the overhead crane operator to guide his lift. The red light indicates “out of level” and the green light indicates “level”. Specifically, red light 221 indicates that the load bar is outside a preset level of tolerance, and green light 222 indicates that the load bar is within the preset level of tolerance. The overhead crane operator stops his winch if the red light illuminates and gives the load bar a longer time to automatically level. When the green light illuminates, the load bar is at its tilt set-point plus or minus the operational angular tolerance selected. An additional safety feature of the invention is that the motion power enable signal 220 must be alternated on and off to keep the power on the motors. A failure in either state will open a hardware watch-dog relay, causing the machine to stop. Further, red light/green light 221 / 222 is visible to at least one of ground personnel and bridge crane personnel. Moreover, red light/green light 221 / 222 flashes when the motors are deactivated, for example when a deadman switch is released.
[0021] A ground control unit is provided for use by the ground operator responsible for moving the load. This unit is mounted on a mobile cart or in a self-contained operator pendant so that it can be available at the pickup and delivery points of the overhead crane. FIG. 3 is a block diagram of the ground unit. It includes a radio transceiver 301 for communications with the under the hook equipment of FIG. 2 . The power 303 for this radio can be removed by pressing an E-stop button 302 . E-stop 302 is controlled by an independent computer with its own independent set of sensors. The resulting loss of communications will be sensed by the load bar that will then remove power from the drive motors. The mobile cart includes a PC system unit, an LCD color touch screen, a keyboard used for set-up functions with alpha characters, an e-stop button, a deadman switch, a digital radio, a power supply, a power switch, and a line cord. In the exemplary embodiment the line cord is 30 feet long. A battery back-up is used to eliminate the cord in cases where more mobility is required.
[0022] A network switch 304 connects an embedded controller 308 and a personal computer system unit 305 to the radio. The purpose of the embedded controller is to provide a reliable path for the deadman switch 309 to respond to messages from the safety computer 205 (shown in FIG. 2 ). In the exemplary embodiment, dead man switch 309 is coupled to the mobile cart and includes a 30 foot cord. This is done because PC off-the-shelf software is not accepted as being sufficiently safe for such a critical function. Deadman switch 309 allows an operator to turn the motors on or off as required during any tilt or XY operation.
[0023] The PC based touch-screen application software is an integral part of this device and supplies several key elements, described herein below, for the ease of operation and safety of the invention.
[0024] Log-in passwords are required for operators as shown in the password screen (shown in FIG. 4 ). The purpose is to help ensure that the equipment is used only by personnel who have been trained properly.
[0025] The red light 221 /green light 222 sensitivity setting can be adjusted on the password screen (shown in FIG. 4 ). When a load has to be controlled with higher angular precision, the red light/green light sensitivity can be set to a fraction of a degree. When less precision is required the sensitivity can be relaxed permitting the crane operator to lift/lower more rapidly.
[0026] The main screen for tilt operations is shown in FIG. 5 (tilt screen). This screen allows the operator to set a reference plane suitable for the load being lifted. Touch buttons make the setting operation easy. When lifting occurs, the pitch and roll tilt angle dialed in by the operator will be automatically held as long as the momentary-action deadman switch 309 is held closed. In the exemplary embodiment, users have two modes of control, tilt and XY. Specifically, tilt is shown on the tilt screen (shown in FIG. 5 ) and moves the motors to eliminate a deviation from a desired tilt. XY is shown on an XY screen and moves the motors to control movement of the load bar in the X and Y directions.
[0027] A learning feature is also included in the exemplary embodiment. The learning feature permits the balance coordinates in X and Y to be recorded for a load and given a name. The invention can recall these recorded settings to save time when the same component is lifted again. FIG. 6 (preset screen) is the application screen provided for this purpose.
[0028] Further, the invention includes dual acme drives. Specifically, the load bar includes two acme screws on each axis. Each screw includes a motor, an amplifier, and a computer. Since the screws cannot be back-driven, if either independent system tries to “run away” or operate erratically the system will physically lock.
[0029] In the exemplary embodiment, the invention also prevents transmission errors. Specifically, the radio transmissions have an extra level of software encoding to ensure legitimacy of transmissions. Received transmissions are interpreted by all three on-board computers, which must agree to operate.
[0030] Further, an embedded safety computer is used in the mobile cart to check the validity of messages from less reliable software. The embedded safety computer handles the safety functions of the deadman switch and E-stop.
[0031] 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 is provided for assembling a load bar assembly. The method includes providing a first linear stage having a first alignment mechanism that is configured to move the load bar assembly in a first direction. A second linear stage is provided that includes a second alignment mechanism that is configured to move the load bar in a second direction that is different from the first direction. The first alignment mechanism is positioned with respect to the second alignment mechanism such that the first alignment mechanism and the second alignment mechanism are prevented from being back-driven. The first alignment mechanism and the second alignment mechanism are configured to lock if one of the first alignment mechanism and the second alignment mechanism fails.
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BACKGROUND OF THE INVENTION
A pump diaphragm, which forms a part of the dispenser mechanism, is known, for example, from U.S. Pat. No. 4,457,454. In this case, it was a matter of a dome-shaped body made of flexible material, with a central conduit for the product mass as well as a central inlet for the power to push the pump membrane back and forth.
A dispenser of the general type with which the present invention is concerned is disclosed in DE-OS No. 34 35576. There the piston, which is sucked upward during the course of the progressive reduction of the volume of pasty product before it, has a closable air-venting nozzle. Through this nozzle the air trapped between the surface of the product and the wall of the piston, during the insertion of the same, is able to escape. The filling operation is carried out with the dispenser in an inverted position, with the head pointing downward. A reclosing is needed in order to make it possible to generate the partial vacuum within the housing necessary for the later operation of the dispenser mechansim. In the case of the known solution the closure of the air-venting nozzle is accomplished by means of a stopper or plug. But due to the fact that there must be sufficient adhesion to hold the stopper in place, or even because some sort of snap-locking arrangement is necessary, the product mass is subjected to considerable stress. This can lead to an unwanted squeezing out of the same, for example, in the case of an improperly closed discharged nozzle. In the effort to improve the manageability of the rather small stopper, the latter is equipped with a large, frequently troublesome handling lug in the form of a disk.
SUMMARY OF THE INVENTION
The object of one aspect of the invention is to optimize a dispenser with regard to both manufacture and function and to provide a dispenser with a high degree of functional reliability, which offers advantages from the point of view of structure and assembly. There results a considerable degree of independence of the viscosity level of the product mass or masses and the associated recovery capacity of the pump diaphragm in its output position. The correspondingly high recovery forces are based upon the radially oriented corrugation of the surface of the pump diaphragm, that is to say, of the depressible segment of the pump diaphragm. The correspondingly extensive corrugation produces surfaces of different heights, which are joined via abrupt transitions and thus result in a surprisingly efficient reservoir of energy. There is thus no longer a purely annular, that is to say, rotation-symmetrical deflection of the diaphragm; on the contrary, a completing cross-wise movement occurs in the plane of the arch. The correspondingly polydirectional deformation is also a significant source for the high level of stored energy. One configuration, which is particularly economical in terms of material and nevertheless highly effective, is produced by the simple expedient of forming the corrugation via the molding of the pump diaphragm. Covered by the term molding is a uniform initial thickness of the diaphragm, where the corresponding corrugation-counterpart results on the inner side of the diaphragm. An additional advantageous structural feature is that the surface of the pump diaphragm is subdivided into individual prominent fields, separated by grooves with hollow ridges lying along the radii. The radial ridges, when distributed at equal angles, function more-or-less like the spokes of a wheel; that is to say, they produce zones of equal loading. The hollowing of the ridges creates a virtually spring-free space.
A related feature, which is favorable from the point of view of molding technology, is that the hollow ridges project from the outer surface of a molded central barrel. The hollow shape produces a line-like root area by means of which a partial anchoring in the axial direction of the barrel results. Accordingly, the forces of deformation also pass over into this barrel-anchoring region. In other words the barrel is also at least partially involved in the deformation and thus also contributes to the reserve of spring energy. Likewise favorable to ease of molding is the fact that the hollow ridges are open at the bottom surface of the pump diaphragm. This, combined with the fact that the bottom of the grooves join upper side are convexly arched, produces a stabilization of the grooves and at the same time an enhanced degree of corrugation. The fields remaining between the ridges, which are preferably positioned at equal angles with respect to one another, have a sectorial shape. These fields each have a nearly trapezoidal outline but with a rounded base towards the perimeter. The prominent corrugation produced makes it even possible to form the pump diaphragm as an integrally molded part of the interior wall of the housing. The spring capability, which is attributable essentially to the shape of the energy reservoir, results even in those cases where the structural material is relatively hard, as, for example, in the case of polypropylene. Such material is highly suitable for the production of the tubular housing.
A structurally particularly simplified arrangment of the dispenser mechanism is achieved by making the barrel the carrier of the discharge nozzle. The barrel thereby assumes a further function, for example that of a mounting plug. In this case, the end of the discharge nozzle facing the barrel would then form a corresponding receptacle. The wall of such a receptacle would then stabilize the segment of the barrel comprising the male coupling in the manner of an external collar. An easy and convenient manipulation of the dispenser mechanism is afforded by an additional feature, namely, that a rocker lever, which carries the actuating key, engages the discharge nozzle. It is thereby advantageous that the barrel, along with the discharge nozzle, be angled in the direction of the rocker arm level pivot, thus forming an acute angle with respect to the central axis of the housing. In the case of a correspondingly coaxial arrangement of the barrel and discharge nozzle, this puts the discharge nozzle opening or orifice in a decentralized position, closer to the edge, permitting the precision application of the product to the delivered in metered quantities to the desired object, for example to a toothbrush. A further variation, advantageous from this point of view, is that the pump diaphragm with its rim be eccentrically mounted in the housing, in which case, for an extremely decentralized positioning of the opening of the discharge nozzle, it is expedient to relocate the assembly from the middle to a position closer to the rocker-arm lever pivot. It is further advantageous that the barrel of the pump diaphragm lie at an acute angle with respect to the plane passing through the rim of the pump. It is further helpful that the discharge nozzle be joined to the rocker-arm lever by means of at least a flexible segment. Such attachment points should lie diametrically opposite one another and obviously at right angles with respect to the plane of movement of the rocket-arm lever. A supplementary function is taken over by the barrel of the pump diaphragm if the top end of the barrel is equipped with a flap valve, which closes off only a part of the cross-sectional area of the discharge nozzle. The top edge of the barrel will thus form at the same time the seat for said valve. The portion of the cross-sectional area remaining open, on the other hand, is subdivided into channels, which are arranged to the outside of a tube seated in the barrel. Such an arrangement permits a stripe-like application of a supplementary or secondary product mass to the strand of product exiting the discharge nozzle. The supplementary product mass could, for example, be mouth wash component to be attached to a toothpaste. The secondary product is superimposed upon the principal product mass. The central tube, which is positioned in the barrel, passes down through the region of the mass of secondary product and forms the discharge bridge for the principal product mass, which has greater volume. Furthermore, it is advantageous, particularly in the case of a dispenser arranged according to claim 1, that the discharge nozzle be mounted so as to permit longitudinal movement in a shaft of the housing-head piece and with a portion of the top edge of its wall fashioned into a cutting edge, operating against the cap of the shaft, in order to part the extruded strand of product. The edge of the wall impinging upon the cap acts like a knife. Any smearing is virtually impossible. This operation can be effected with the use of a certain loading of the diaphragm body, which at the same time forms a return spring, not only moving the parting knife into the self-closing position but also supplying return force for the rocker-arm lever.
The present invention also makes possible the simpler and more rapid assembly of the dispenser by the provision of a follower piston having a unique air-venting construction which permits initial installation of the piston without discharge of the product within the dispenser. The wall of the air-venting nozzle itself provides the site for closure via the simple closure-bonding of the surface of the inner wall of the nozzle. There are fewer defective closures since it is no longer necessary to make use of a structural element requiring precise positioning. It is advantageous if, for example, the nozzle inner wall is cemented together. In the case of a permanently deformable material the closure can be effected by simple deformation of the nozzle wall. On the other hand it is possible, via appropriate mechanism means to apply, for example, a drop of rapidly hardening adhesive. One particularly advantageous solution is to provide the air-venting nozzle with an outwardly and downwardly projecting deformation segment. There is in this case always free and largely tolerance-independent access for the head of the machine. The correspondingly exposed position of the air-venting nozzle allows it to be accommodated on the piston without spatial difficulties. Closure-bonding via a pinch-welding of the air-venting nozzle is preferred in combination with a thermically suitable material. In view of the fact that nearly all parts of most dispensers of this type are made from thermoplastic plastic, this means of closure is the most recommended. When, for example, the pinch welding is effected in an axial direction via the application of a heating element to the deformation segment, no stress is imposed upon the product in the sense of the squeezing force discussed above, the contact heat escaping rapidly from the point of application. Moreover, the power needed to operate the welding tool is extremely small and by no means comparable to that needed for snap-locking against opposing force. A particularly secure, thermally induced drawing together of the nozzle orifice results if the top edge of the nozzle wall is beveled to produce the approximate shape of a cone. The beveled edge tapers inward, toward the center. The corresponding sloping surface promotes the self-location of this lip segment in the processing machinery.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a vertical cross-section of the dispenser shown in the rest position, with the air-venting nozzle still open;
FIG. 1a shows the air-venting nozzle in the closed state;
FIG. 2 shows the upper portion of the dispenser in the discharge position;
FIG. 3 is a perspective view of the pump diaphragm by itself;
FIG. 4 is a section along line IV--IV of FIG. 2;
FIG. 5 is a vertical section through a modified version of the dispenser in the rest position;
FIG. 6 is a similar view but in discharge position;
FIG. 7 is a section along line VII--VII of FIG. 5;
FIG. 8 is a section along line VIII--VIII in FIG. 5;
FIG. 9 is a section along line IX--IX in FIG. 8; and
FIG. 10 is a section along the line X--X in FIG. 5.
DETAILED DESCRIPTION
The housing 1, which has the shape of a long cylinder, contains a pasty principal product mass I, which occupies the greater share of the volume and is superimposed by the mass of supplementary or secondary product II, accommodated in the head region. The material constituting principal product mass I can be a toothpaste. The secondary product mass II is, for example, a mouth wash component, likewise a material having a pasty structure. It is applied in the form of stripes to the strand passing out through the opening O in the head region and can be colored.
Output is effected by means of a pump mechanism D, lying in the dispenser head which forms a pumping chamber with a pistion 2, positioned beneath the principal product mass I, which can be displaced incrementally in the direction of discharge, that is in the direction of the arrow X. The edge lips 2' of the piston provide sealing action as they pass along the cylindrical interior wall of the housing 1'. The piston has the shape of a cup. The edge lips 2', united by means of a transverse wall 2", taper outward in opposite directions. The housing 1 is open at the bottom. It is filled from that direction. The supplementary or secondary product mass II, having the smaller volume, is filled in first, then the principal product mass II. This all takes place with the dispenser inverted, the head pointing downward. After filling, the piston is inserted into the housing from the open side of the dispenser. The air trapped between the surface of the mass of principal product I and the piston 2 is forced out by way of escape zones. Known methods for accomplishing this include, for example, the roughening or lengthwise grooving of the first part of the interior wall of the housing. Another proposal is to provide, during molding, for a central nozzle to permit the escape of air, which is then closed by means of a plug.
In the case of the illustrated embodiment of the invention, the piston 2 is equipped at the center with an air-venting nozzle T. This is an integrally molded part of the piston 2. The air-venting nozzle T is a small tube 3 projecting from the lower face 2' of the piston 2 and initially bored all the way through, which is positioned at the highest part of the bulkhead or lower face 2" of the piston 2 in order to allow all of the air to escape and thus prevent the formation of air bubbles. This evacuation, once completed, is followed by the closure-bonding of the inner surface 3' of the nozzle wall, effected via the deformation of the wall material. Closure in the case of a metal tube is effected by means of the radial pinching of the metal. But if the piston is made of a thermoplastic material, a pinch-weld is employed to seal the air-venting nozzle T. In any case, the tube 3 projects far enough from the body of the piston to provide a large easily accessible deformation segment for closure. The operation of closure takes place without imposing any force upon the piston, that is to say, without the need to impose any force in the direction of the product I/II, which could squeeze it out. The deforming operation makes use of the application of radially inwardly directed forces to the outer wall of the tube. The thermic melting back of the deformation segment of the air-venting nozzle T is effected in an essentially axial direction and takes place so spontaneously that the corresponding axially moving melt puddle encounters virtually none of the resistance leading to the imposition of stress upon the product. It is here advantageous that the outer edge 3" of the nozzle wall be tapered into a cone. The base of the cone is turned toward the lower face 2" of the piston 2. A rotation-symmetrical annular tip is thus melted back, by a unit which practically guides itself into the opening in the tube. The closed position is illustrated in FIG. 1a.
Although the piston 2 already provides the lower closure of the product reservoir chamber, that is to say, the closure facing the surface ST, it is nevertheless possible to snap-lock a cover disc 5 into the region of the outwardly expanded base-rim 4 of the dispenser (see FIG. 1). The cover disc 5 has a laterally positioned vent opening 6.
The travel of the piston 2 in one direction only is achieved by locking means G. In the case of the dispenser according to FIG. 1, this is a so-called clamp module 7 in the form of a star, made of spring steel, with a prong 7' oriented in a radially outward direction. The diameter spanned by the prong ends, projected into one plane, being somewhat larger than the interior diameter of the housing 1, the prong ends, acting as angled supports against the housing inner wall 1', prevent the movement of the piston in the direction opposite that of the arrow X. The clamping module lies at the back of the piston, that is to say, on the side turned toward the surface ST. The mounting of the same can be effected by the use of heat by providing meltable lugs, which project through holes in the module and are then melted to form rivets.
In the case of the dispenser shown in FIG. 5, the locking means G are an integral part of the piston 2. Here it is a matter of a so-called ratchet. Projecting form the transverse wall 2" of the piston 2 and equidistantly arranged around the perimeter of the same, on the side turned toward the surface ST, are ratchet fingers 8. These radiate outward from said transverse wall 2" to form the annular wall 9. The distal ends of the ratchet fingers 8 exhibit a cross-wise corrugation 8'. This latter consists, when viewed in cross-section, of more-or-less sawtooth-like segments comprising screw threads. The ridges of the same 9' mesh with horizontal but correspondingly shaped tooth gaps 10' of the serrations 10, molded into the interior wall 1' of the housing. The support function is provided by the horizontal, steep flanks of the diametrically opposed serrations 10, while the adjacent, angled sides permit the relatively frictionless travel of the piston 2 in the directin of the arrow X. The extensive separation of the finger crown forming the ratchet fingers and the axial movement, produced by screw-pitch, of the crosswise corrugation 8' of the piston 2, in the case of a purely horizontal orientation of the tooth gaps 10', produces in every instance a secure support interlock, even if the distance through which the piston is lifted is less than the axial length of a tooth interval. Each of the serrations covers in the horizontal plane an angle of arc of less than 90 degrees, so that several of the peripherally roughened ratchet fingers 8 impinge upon a smooth section of the interior wall 1' of the housing.
The edge lips of the piston 2 radiate outward likewise here; but the contact surface of the inner wall is greater than the distance between the apex of one tooth and that of the next of the serrations 10 so that sealing is effected as the piston travels.
The pump mechanism D positioned at the opposite end of the dispenser, at the head, comprises a pump membrane M. The latter is a bellows or deformable element, which can be depressed in the direction of the piston 2 and whose pump diaphragm surface wall 11 always returns spontaneously, on being released, to its rest position, as shown in FIGS. 1 and 5. This element (M) is either produced as a separate structural part (see FIG. 3) or is molded as a materially integral part of the housing 1, in the head region. This latter arrangement is possible due to the peculiar surface structure of the pump diaphragm M, which permits it to function properly in spite of the relative hardness of the material forming the housing. The passage of the product is via the center by way of a discharge nozzle 12, which is a free-standing structure projecting above the upper side of the pump diaphragm M.
The special surface structure of the diagphragm consists of the corrugation of its surface oriented along the radii. This is shown in FIG. 3. As illustrated, the rotation-symmetrical corrugation of the diaphragm surface creates regions with different axial heights. The radial orientation is particularly evident in FIGS. 8 and 10. It is created by the molding of the surface wall 11 of the pump diaphragm, which has approximately the same thickness throughout.
Form-determining elements of the radially oriented structure are the hollow ridges 13, at equal angular intervals, which divide the surface into five parts. Extending between the ridges 13 are the grooves 14, with a V-section though rounded at the bottom, and the adjacent fields 15, which virtually fill out the intervening space. Seen from the above (FIGS. 8 and 10) the fields are prominent. The plane of the plateau-like fields 15 is approximately that of the spines of the hollow ridges 13. The spines of the hollow ridges and the upper side of the fields 15 are thus the higher portions of the essentially slightly concavely arched pump diaphragm surface wall 11, while the bottoms of the grooves 14 and peripheral area surrounding the fields 15 are assigned to a more deeply lying portion, that is to say, to one forming another plane. The U-shaped ridges 13, open in the direction of the product mass, are rooted in the outer surface of a centrally molded barrel 16. The latter has a cylindrical cross-section and projects above the upper side of the pump diaphragm surface wall 11 and prossesses a diameter, which is approximately one quarter of that of the pump diaphragm. However, the fields 15, with their sector-like outline and shape approaching approximately that of a trapezoid, are clearly set back from the outer surface of the barrel and pass under a circumferentially wavery ring groove into the downwardly oriented end of the barrel 16. This produces a definite fold ring a (FIGS. 2 and 5). The external fold ring is designated with b. It forms the rim of the pump diaphragm surface wall 11. Projecting from this rim is an axially oriented wall 17, which in the case of the embodiment shown in FIG. 5 is attached to the housing 1 via an annular shoulder 18.
In FIG. 1 this horizontal shoulder 18, which is perpendicular to the lengthwise central axis X--X of the dispenser, is continued upward in the form of a cylindrically shaped, upwardly projecting collar 19 onto which the pump diaphragm M, executed as a separate structural element, is clipped or snapped. The annular wall 17 of the diaphragm has a protuberant snap-lock ring 17' on its inner edge, which interlocks with a corresponding snap-locking groove 19' of the collar. The lower edge of the annular wall 17 thereby abuts the upper side of the annual shoulder 18.
The ridges 13 and their U-shaped zone of transition with the outer wall of the barrel 16 and the relieved or corrugated surface, formed by elements on different planes, combine to produce a powerful energy reservoir, in which case the portions representing the fields 15 create partial steepening, but the margins or sides of these fields, seen from the edge, create a practically zig-zag structure, with elements of different side length. In the compressed state, the U-legs of the radially oriented hollow ridges 13, which have the shape of a U when viewed in cross-section, enter into a diverging fold position, so that flexing points, comparable to those at a and b, result also in the direction of the periphery. A further measure to increase the spring-energy storing capacity of the pump diaphragm M, which has the appearance of a wheel due to the radially oriented hollow ridges and the hub-like barrel, consists in the fact that the bottom of the grooves, viewed from the upper side, is convexly arched. This optional feature is indicated in FIGS. 1 and 5 by dot-dash lines. The extended position of the bottom of the grooves 14 is shown by means of solid lines.
The upper end of the barrel 16 arises the discharge nozzle 12, the latter being either an integral part of the same or a separate tubular nozzle element, as shown in the drawings. The means of attachment in the latter case is a plug-socket arrangement. A press fit is employed. The attachment end of the nozzle element forms a receptacle or socket 20 to receive the upper end of the barrel 16. The socket portion has a larger diameter than the remainder of the discharge nozzle 12.
The downward stroke of the pump diaphragm M is effected by means of an actuating mechanism B adjacent to the discharge nozzle 12. This is formed by a single-armed rocker-arm lever 21. The latter, viewed in cross-section, has the shape of a U. It is a molded part whose outer end is raised to form an actuating surface 22. This region is in the U-ridge zone, whereas the free ends at the parallel U-legs of the actuating device terminate in a rocker-arm pivot 24. This pivot element 24 is constituted by a projecting lug 15 of a snap-locking head-piece 26 of the housing. A hook-shaped terminal segment 27 of the U-legs 23 snaps under the stationary lug. The rest position is stop-defined.
The actuating mechanism B is retained in the rest position by the resilient pump diaphragm M. It is possible here to exploit a slight pretensioning. The coupling between the pump diaphragm M and the actuating assembly B is accomplished by molded elements. These include two coupling segments 28, which are positioned on diametrically opposite sides of the outer jacket of the plug-in socket 20 of the discharge nozzle 12. These segments 28, per an outwardly directed course, pass into curved segments 29, which run parallel to the discharge nozzle 12. These curved segments 29, which are positioned upon the U-legs 23, are of such a length that they compensate for the differing courses of movement of the actuating assembly B and the pump diphragm M.
FIG. 5 illustrates another embodiment in which the dispenser head is formed by an extension of the housing 30 in the direction of the head. Here, too, the free end of the discharge nozzle 12 projects upward above the unit. The designation numbers employed are those used for the corresponding parts in the other embodiments.
Although here at least the case of the discharge nozzle 12 coincides with the central axis X--X of the dispenser, the outboard end of the nozzle 12 is bent to form an upwardly inclined terminal segment, which makes an angle of approximately 30 degrees with the horizontal. A closure cap 31, forming a part of the extension of the housing 30, can be removed for the purpose of discharging the contents. In this latter case it occupies the position shown in FIG. 6. When closed, the cap secures the mechanism against movement since the cap forms a socket to receive the cylindrical tip of the discharge nozzle 12.
In the embodiment shown in FIG. 1, the barrel 16, along with the coaxially attached discharge nozzle 12, is angled in the direction of the rocker arm lever pivot 24 and forms an acute angle with respect to the longitudinal central axis X--X of the housing. The axis of the barrel carries the designation Y--Y. The acute angle alpha is approximately 15 degrees. As a result of this angular arrangement the orifice of the discharge nozzle 12 is closer to the periphery of the housing than it would otherwise be, making possible a more precise aiming of the product discharge. Of course, the corresponding lateral respositioning of the nozzle leaves somewhat more room free for the actuating surface 22 of the activating mechanism B. Also evident in FIG. 1 is the fact that the rim of the pump diaphragm M, that is to say, the annular wall 17, is positioned eccentrically within the housing, and likewise in closer proximity to the pivot point 24. It is here also noteworthyl that the barrel 16 of the pump diaphragm M forms an acute angle with respect to the plane passing through the rim of the pump. The rim is higher to the right than to the left. The annular shoulder 18, on the other hand, retains its horizontal position.
Whereas the dispenser of FIG. 5 operates according to the hydraulic principle, as described in EP-PS No. 0051790, the dispenser per FIG. 1 makes use of a valve flap 33. The latter is molded as a freely standing structure within the discharge nozzle 12, at the level of the socket 20 and projects into the cross-sectional area of the nozzle. The material of the valve flap 33 is thinner at the point of attachment in order to increase its flexibility, the result being the film hinge 34. The top edge 16' of the barrel 16 forms the seat for the valve.
The valve flap 33 closes off only a portion of the cross-sectional area of the discharge nozzle 12 or of the central opening 35 of the pump diphragm M. The area remaining at the periphery, an annular zone interrupted only by the hinge 34, has channels 36, which are parallel with the opening 3. As shown in FIG. 4, the channels 36 are uniformly arranged.
The channels 36 are positioned externally with respect to a tubular element 37, mounted within the barrel 16. The outer wall of this tube 37 is radially separated from the corresponding cylindrical interior wall 16" of the barrel 16, the outer wall being therefore surrounded by secondary product mass II in the zone near the barrel of the pump diaphragm M. The channels, arranged in a ring, extend upward from this point. The free end of the tube 37, on the other hand, dips down into the mass of the principal product 1. The tube 37 thus constitutes a discharge bridge for this mass, while the hood-like diaphragm body provides the reservoir for the mass of supplementary or secondary product, which, on passage through the channels 36, is deposited in the form of stripes upon the product strand being discharged. The supplementary product mass II benefits from the back-filling pressure of the principal product mass I and, with the gradual removal of the latter, is lifted in the direction of discharge, that of the arrow X. The volume compensation is such that the quantity present of supplementary or secondary product II is consumed as the principal mass is discharged.
In order to keep waste to a minimum, the cross wall 2" of the piston 2 has been designed to conform as closely as possible to the inner contour of the pump diaphragm. it possesses, on the side facing the nozzle, protuberant structures 38, with a central recess 39 to receive, without interference, the lower end of the relatively long tube 37.
The dispenser mechanism per FIG. 1 slides into a shaft 40 of the housing-dispenser head 26. This shaft 40 is closed at the top. The corresponding sloping roof carries designation number 41 and is called the cover. The pertinent end of the discharge nozzle 12 projects like a chimney above the upper side of the pot-shaped head-piece 26, which has openings for the actuating mechanism and the discharge nozzle. The orifice O of the discharge nozzle 12 is correspondingly angled, the sides being parallel to one another, the angle being measured with respect to the lengthwise central axis X--X. These parts are shaped and arranged in such a way that a portion of the upper edge of the discharge nozzle 12 is able to function as a cutting edge against the inner side of the cover 41 of the shaft 40, in order to part the extruded strand of product. Depending upon the contour chosen for the distal end of the discharge nozzle 12, this cutting edge can be either a round knife or a flat knife. In the case of the illustrated embodiment the initially round lower portion of the discharge nozzle 12 gradually assumes an approximately quadrilateral cross-section. In any case, the parting cut is so precise that no residues remain. A correspondingly precise shaping of the product strand results in turn.
The dispenser illustrated in FIG. 1 is covered protectively with a cap 43. The latter can be molded with an annular bead 44 at the rim to prevent tampering with the product prior to sale. The annular bead 44 fits over the rim 26' of the mounted head-piece 26. The annular head has a steeper and a flatter side. The flatter side facilitates the snapping of the cap 44 onto the head-piece 26. Associated with the annular bead 44 is a parting groove 45. Removal of the anti-tampering seal, which has the form of an annular band, is effected by a pull-tab 46, which is free-standing but does not project beyond the rim of the cap 43 and is straightened with reference to the support surface ST. The diameter of the rim in question is equal to that of the base flange 4. The projecting outer surfaces of these bands protect the sides of the housing by keeping adjacent containers at a distance, whether in shipping package or on store shelves. The labelling applied to the cylindrical surface of the housing 1 is always thereby optimally protected.
The dispenser operates as follows:
Following removal of the cap 43, the actuating key B is depressed. This produces a deformation of the pump diaphragm surface wall 11. The latter also functions as a return spring. The pressing down diminishes the volume in the dispenser interior. Both the supplementary or secondary product mass II and the principal mass I are submitted to pressure. The mass of principal product I passes through the tube 37 into the discharge nozzle 12 and out finally through the orifice O. The superimposed secondary mass II flows through the channels 36 into the region forming the nozzle. This secondary product II is then applied to the outer surface of the exiting strand of principal product I in the form of stripes. The valve flap 33 does not stand in the way during the pressing out of the mass of product. It is pushed out of the way by product, pivoting on the hinge 34.
On release of the actuating mechanism B, a partial vacuum develops within the housing I. The pump diaphragm returns to its position of rest and draws the piston 2, including the product before it, upward in the direction of arrow X. In the case of the unit illustrated in FIG. 5, the return of product still within the discharge nozzle 12, is withdrawn from the tube 37. To that extent, a valving function takes place at this point. This function is further promoted by the expansion of the interior diameter in the upper segment of the discharge nozzle. The arising partial vaccum effects in the case of the unit in FIG. 1 the closure of the valve flap 33 so that here, too, the piston 2 is drawn upward.
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The invention concerns a dispenser for the metered delivery of materials in paste form, with a tubular housing in which a follower piston in incrementally displaceable in the direction of discharge, and with an actuating key, positioned adjacent to a discharge nozzle, for the displacement of the surface of a pump diaphragm, fastened at its edges, from its rest position in the direction of the follower piston. The follower piston has a closable air vent. The pump diaphragm has a series of radially extending formations which materially increase its recovery capacity following a pumping stroke.
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BACKGROUND
The present invention generally relates to trailers. More specifically, the present invention relates to a trailer with an anchor system for securing large generators for transport.
Large generators are used at sites as temporary power. The generators are so large that a trailer is required to transport such a generator to and from a site, where it remains mounted. A trailer is also required to transport such a large generator that is to be installed temporarily at a site, until further decisions are made regarding utility. Typically, the generator is bolted or welded to the trailer to anchor the generator to the trailer, during transport. This increases the time and complexity to secure and remove the generator when using a trailer. When the generator is bolted to the trailer, specific wrenches are needed to secure or loosen the bolts holding the generator to the trailer. The use of bolts requires a person with enough strength to tighten and loosen the bolts, which could lead to strain type injuries to the person performing such a task.
It is an object of the present invention to provide a trailer with an anchor system for a generator which provides an easy process for securing and unsecuring the generator in relation to the trailer.
SUMMARY OF THE INVENTION
A generator trailer with anchor system adapted for transporting a large generator. The trailer has a bed with a front, rear and two sides surrounding the bed. There are at least four tightening devices. Each of the tightening devices includes a trailer component, an adjustable tension component and a generator component. The trailer component attaches to the trailer. The generator component is adapted to be attached to the generator. The adjustable tension component attaches between the attached trailer component and the attached generator component to provide tension to secure the generator to the trailer and provides a quick disconnect from the generator.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a perspective view of a trailer with an anchor system according to the present invention.
FIG. 2 is a perspective view of a trailer with an anchor system according to the present invention.
FIG. 3 is a perspective exploded view of a trailer with an anchor system according to the present invention.
FIG. 4 is a perspective view of a trailer with an anchor system according to the present invention.
FIG. 5 is a perspective view of a tightening device according to the present invention.
FIG. 6 is a perspective view of a tightening device according to the present invention.
FIG. 7 is a perspective view of a tightening device according to the present invention.
FIG. 8 is a perspective view of a trailer with an anchor system according to the present invention.
FIG. 9 is a perspective view of a trailer with an anchor system according to the present invention.
DETAILED DESCRIPTION
The present invention is a trailer with an anchor system for large generators, as shown in FIGS. 1–9 . The anchor system includes at least four tightening devices. FIGS. 1–2 shows the trailer 10 as a trailer 10 with a bed 12 surrounded by a front 14 , rear 16 and two sides 18 . FIG. 1 shows a generator 20 mounted on the bed 12 of the trailer 10 . FIG. 2 shows the trailer 10 without the generator 20 . The trailer 10 includes extended walls 22 extending upward from the bed 12 of the trailer 10 at the front 14 , rear 16 and sides 18 of the trailer 10 . The bed 12 of the trailer 10 within the extended walls 22 is approximately the same size as the base of the generator 20 . The trailer 10 could also be without the extended walls 22 , such that the bed 12 is even with a top surface 24 of the front 14 , rear 16 and sides 18 of the trailer 10 and the generator 20 sits on the top surfaces 24 . The tightening devices 26 can be mounted two on each side 18 or one on each of the front 14 , rear 16 and sides 18 . The tightening devices 26 are designed to have a quick release feature to simplify attachment to the generator 20 .
Two tightening devices 26 are shown mounted to each side 18 of the trailer 10 . FIGS. 1–6 show a first version of the tightening device 26 and FIGS. 7–8 show a second version of the tightening device 26 . The first version of the tightening device 26 includes a ratchet body 32 and a ratchet mechanism 34 , as shown in FIGS. 3–6 . The ratchet body 32 is mounted to the sides 18 of the trailer 10 . The ratchet body 32 is shown with a bolt hole 36 for bolting the ratchet body 32 in a permanent manner to the trailer 10 . The ratchet body 32 could also be welded or attached by other fastening means to the trailer 10 . The ratchet mechanism 34 is shown as one of many of the standard ratchet mechanisms available which receives the ratchet strap 30 . One end of the ratchet strap 30 attaches to the ratchet mechanism 34 , while the other end of the ratchet strap 30 includes attachment of a clevis 38 . The clevis 38 is shown as a U-shaped clevis which two ends 40 . Each end 40 of the clevis 38 includes a bolt hole 42 . The clevis 38 is attached to the ratchet strap 30 by looping an end of the ratchet strap 30 about the U-shape clevis and sewing the end of the ratchet strap 30 to the ratchet strap 30 , as shown in FIG. 3–6 .
The generator 20 includes attachment points 44 along the sides of the generator 20 for each tightening device 26 and which align between the bolt holes 42 of the clevis 38 . The attachment points 44 include a bolt hole 46 to receive a bolt 48 , as shown in FIG. 6 . The bolt 48 is used to attach the clevis 38 to the attachment point 44 by placing the bolt 48 through one of the bolt hotes 42 of the clevis 38 , through the bolt hole 46 of the attachment point 44 and finally through the other bolt hole 42 of the clevis 38 . A nut 50 is used to secure the bolt 48 in the bolt holes 42 , 46 . The bolts 48 can be replaced by a pin. The pin should have some locking means to retain the pin in the bolt holes 42 , 46 . The ratchet mechanism, 34 is used to tighten the ratchet strap 30 when the clevis 38 is attached to the generator 20 and the generator 20 is to be secured to the trailer 10 . The ratchet mechanism 34 is used to loosen the ratchet strap 30 when the clevis 38 is attached to the generator 20 and the generator 20 is to be unsecured from the trailer 10 . The tightening and loosening of the ratchet strap 30 is performed based on the particular style of ratchet mechanism 34 employed. The end of the ratchet strap 30 attached to the ratchet mechanism 34 can be easily removed from the ratchet mechanism 34 without the use of tools, thereby making it easy to unsecure the generator 20 from the trailer 10 . Also, if pins are used instead of bolts 48 , the clevis 38 can be quickly released from the attachment point 44 of the generator 20 .
The second version of the tightening device 26 shown in FIGS. 7–8 and includes a turnbuckle 52 and two attachment hooks 54 . Each attachment hook 54 includes a hook 56 extending from an attachment plate 58 . Each attachment plate 58 is shown with two bolt holes 60 and two bolts 62 . One attachment hook 54 is bolted to the trailer 10 , while the other attachment hook 54 is bolted to the generator 20 in an aligned manner. The attachment hooks 54 could also be secured by welding them to the trailer 10 and the generator 20 . The attachment hook 54 on the generator 20 acts as the attachment point 44 . The turnbuckle 52 includes a turnbuckle body 64 and two threaded eyes 66 . The threaded eyes 66 each have an eye 68 with a threaded shaft 70 extending from the eye 68 . The threaded shafts thread in and out of ends 72 of the turnbuckle body 64 . Each threaded eye 66 screws into one of the ends 72 of the turnbuckle body 64 , which is typical of a turnbuckle 52 . To secure the generator 20 to the trailer 10 the eyes 68 of the turnbuckle 52 are placed over the aligned hooks 56 attached to the trailer 10 and the generator 20 , as shown in FIG. 8 . The turnbuckle body 64 is then turned to pull the eyes 68 toward the turnbuckle body 64 and hence tighten down the generator 20 to the trailer 10 . To unsecure the generator 20 from the trailer 10 , simply turn the turnbuckle body 64 such that the eyes 68 move away from the turnbuckle body 64 . FIG. 9 is a slightly different version of tightening device of FIGS. 7–8 . FIG. 9 shows a ring 76 attached through a hole 78 in the structure of the generator 20 . FIG. 9 shows a ring 76 attached to a ring holder 80 , where the ring holder 80 is attached to the side 18 of the trailer 10 . FIG. 9 shows the turnbuckle body 64 with two threaded hooks 82 . Whereby, the hooks 82 engage the rings 76 .
While different embodiments of the invention have been described in detail herein, it will be appreciated by those skilled in the art that various modifications and alternatives to the embodiments could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements are illustrative only and are not limiting as to the scope of the invention that is to be given the full breadth of any and all equivalents thereof.
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A generator trailer with anchor system adapted for transporting a large generator. The trailer has a bed with a front, rear and two sides surrounding the bed. There are at least four tightening devices. Each of the tightening devices includes a trailer component, an adjustable tension component and a generator component. The trailer component attaches to the trailer. The generator component is adapted to be attached to the generator. The adjustable tension component attaches between the attached trailer component and the attached generator component to provide tension to secure the generator to the trailer and provides a quick disconnect from the generator.
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RELATED APPLICATION
This application claims priority of U.S. Provisional Patent Application Ser. No. 60/609,659 filed Sep. 14, 2004, which is incorporated herein by reference.
FIELD OF THE INVENTION
The subject invention relates to a gamma-aminobutyramide conjugate and synthesis thereof and, more specifically, to the treatment of neuronal disorders by administering the gamma-aminobutyramide conjugate.
BACKGROUND OF THE INVENTION
Gamma-aminobutyric acid (GABA) and glutamic acid are major neurotransmitters which are involved in the regulation of brain neuronal activity. GABA is a major inhibitory neurotransmitter in the mammalian central nervous system. Meythaler et al., Arch. Phys. Med. Rehabil. 1999; 80:13–9. Imbalances in the levels of GABA in the central nervous system can lead to conditions such as spastic disorders, convulsions, and epileptic seizures. As described in U.S. Pat. No. 5,710,304, when GABA levels rise in the brain during convulsions, seizures terminate.
GABA is present in an estimated 60 to 70% of all the synapses in the brain ( Med. Sci. Bull. 1997; 20(5)). There are two types of receptors, GABA-A and GABA-B. The B receptors appear to be involved in spasticity (Meythaler, Arch. Phys. Med. Rehabil. 1996; 77(6):628–9; Young, J. Neurosurg. 1981; 54(3):300–3), while the A receptors appear to be involved in the control of epilepsy ( Med. Sci. Bull. 1997; 20(5)). In fact, GABA-A antagonists cause convulsions in animal models ( Med. Sci. Bull. 1997; 20(5)) as well as spasticity.
Because of the inhibitory activity of GABA and its effect on convulsive states and other motor dysfunctions, the administration of GABA to subjects to increase the GABA activity in the brain has been tried. Because it is difficult to develop and administer a GABA compound which is able to cross the blood brain barrier utilizing systemic administration of GABA compounds, different approaches have been undertaken including making GABA lipophilic by conversion to hydrophobic GABA amides or GABA esters, and by administering activators of L-glutamic acid decarboxylase (GAD). GAD levels vary in parallel with increases or decreases of brain GABA concentration which have been reported to increase GABA levels.
U.S. Pat. No. 4,094,992 to Kaplan et al. discloses benzylidene derivatives which are useful in the treatment of epilepsy and U.S. Pat. No. 4,361,583 to Kaplan discloses the use of the benzylidene derivatives for use in the treatment of pain. This class of drugs are strong GABA agonists which are effective on both GABA-B and GABA-A receptors.
One specific benzylidene derivative disclosed in U.S. Pat. No. 4,094,992 has the chemical structure 4-[[(4-chlorophenyl)-(5-fluoro-2-hydroxyphenyl)methylene]amino]butanamide and is more commonly known as progabide (SL 76002). Progabide does not appear to cause motor weakness in therapeutic dosages to control spasticity and does not appear to significantly affect cognition. There is some suggestion that progabide is an anti-epileptic agent and that it is also neuroprotective. Polasek et al., Epilepsy Research 1996; 25:177–84; Kulinskii et al., Eksperimntalnaia I Klinicheskaia Farmakologiia 1997; 60:56–8.
As discussed above, there are inherent difficulties in the effective administration of GABA and/or its derivatives to a subject in order to increase brain GABA levels. One of the most pronounced drawbacks of GABA administration is that it does not easily cross the blood brain barrier and, accordingly, does not enter the central nervous system after oral or parenteral administration. The benzylidene derivatives disclosed in the Kaplan et al. patent are considered to be “GABA-mimetic” and are capable of penetrating directly into the brain when administered by oral, endo-rectal, or parenteral routes.
It has been found, however, that, in the brain, when GABA agonists are delivered orally, they may cause some supraspinal activity which may contribute to clinical side effects. For example, for the GABA-B agonist baclofen, it has been found that following oral delivery of the drug that many patients experience central nervous system side effects such as drowsiness, confusion, or memory or attentional problems at the dosages required to reduce spasticity. Young et al., New Eng. J. Med. 1981; 304:28–33; Young et al., New Eng. J. Med. 1981; 304:96–99; Lazorthes et al., J. Neurosurg. 1990; 72:393–402; Sandy et al., Clin. Neuropharm. 1985; 8:294–295. Other central nervous system side effects of GABA agonists have included hallucinations, ataxia and memory impairments. Sandy et al., Clin. Neuropharm. 1985; 8:294–295; Hattab, Spasticity, Disordered Motor Control 1980; Roy et al., Paraplegia 1986; 24:318–321. Additionally, the sudden withdrawal of orally delivered GABA compounds may itself lead to seizures and hallucinations. Terrence et al., Arch. Neurol. 1981; 38:588–589.
The side effects noted above with the systemic administration of GABA agonists can be largely averted by utilizing intrathecal drug delivery since intrathecal delivery of GABA compounds to the lumbar or mid-thoracic spinal intrathecal space concentrates the medication in the lower area of the spinal cord cerebrospinal fluid at much higher levels than those attainable via the oral route of administration (Meythaler, McCary, Hadley, J. Neurosurg. 1997; 87(3):415–9). Typically, the type of delivery system for intrathecal therapy consists of a subcutaneously placed pump having a reservoir which is attached to an intraspinal catheter. This drug delivery methodology concentrates the medication within the spinal subarachnoid space and the thoracolumbar and sacral spinal regions at a much higher level than that attainable via the oral route of administration. Meythaler et al., J. NeuroSurgery 1997; 87:415–9. From the subarachnoid space, the cerebrospinal fluid then flows to the arachnoid villi for reabsorption thereby avoiding a significant part of the cerebral hemispheres. Meythaler et al., Arch. Phys. Med. Rehabil. 1996; 77:461–466. Only low levels of the medication have the potential to reach the brainstem or cerebrum as studies have demonstrated the lumbar-to-cisternal drug cerebrospinal fluid (CSF) drug concentration gradient is 4.1:1. Kroin et al., Parenteral Drug Therapy in Spasticity and Parkinson's Disease 1991, pp. 73–83. By utilizing intrathecal drug delivery, the cognitive side effects of oral drug delivery, such as drowsiness and lethargy, can be avoided. Coffey et al., J. Neurosurg. 1993; 78:226–232; Penn et al., N. Engl. J. Med. 1989; 320:1517–1522; Knuttson et al., J. Neurol. Sci. 1974; 23:473–484. Furthermore, intraventricular delivery does the same for the periventricular area or region of the brain.
Preclinical animal studies in a canine model of the GABA-B agonist, baclofen (2000 μg/d for 28 days), intrathecally through a subcutaneously implanted pump demonstrated no deleterious histopathology in the studied animals. (Sabbe, Neurotoxicology 1993; 14(4):397–410). Initial work examining the use of GABA agonists both by systemic delivery and by intrathecal delivery in animal models revealed that baclofen produced a dose dependent analgesia (Bergmann; Clin. Neuropharcol. 1985; 8:13–26; Wilson et al., European J. Pharmacol. 1978; 51:323–330) and a reduction in motor tone in normal (Bergmann; Clin. Neuropharcol. 1985; 8:13–26; Wilson et al., European J. Pharmacol. 1978; 51:323–330; Kroin et al., Exp. Brain Research 1984; 54:191–194) and genetically spastic animals (Klockgether et al., Neurosci. Lett. 1989; 97:221–226).
Based on electrophysiology and the above-discussed preclinical studies, the mechanism of the anti-spasticity associated with intrathecally delivered baclofen is believed to be due to the hyperpolarization of motor horn cells. After the development or onset of upper motor neuron lesions, a variety of long term changes are observed in the brain. Mendell, Physiological Reviews 1984; 64(1):260–324. Among these changes, there is an increase in Ia motor unit activity. Wilson et al., European J. Pharmacol. 1978; 51:323–330. In humans, while motor horn cells show little change in recurrent inhibition after spinal injury, there is a loss of regulation of Renshaw cell inhibition (Katz et al., Brain 1982 March, 105(Pt 1):103–24) and an increased motor neuron excitability (Shemesh et al., Paraplegia 1977 November, 15(3):238–44).
Despite the initial success of the intrathecally delivered GABA agonist baclofen in treating the dystonia/spasticity associated with spinal disorders (Meythaler et al., Arch. Phys. Med. Rehabil. 1999; 80:13–9; Penn et al., N. Engl. J. Med. 1989; 320:1517–1522; Muller et al., Local - spinal therapy of spasticity 1988, pp. 223–226), there is still little interest in treating cerebral disorders with intrathecally administered GABA agonists. This lack of interest appears to stem from the lack of success with oral medications in the treatment of dystonia/spasticity resulting from traumatic brain injury (Katz, Phys. Med. Clin. N. Am. 1992; 3:319–335; Mann, J. Neuro. Rehab. 1991; 5:51–54; Katz, Am. J. Phys. Med. Rehabil. 1988; 67:108–116). However, there were indications from some reports that this may be a useful methodology to improve the functional outcome of traumatically brain injured patients. Meythaler et al., J. NeuroSurgery 1997; 87:415–9; Meythaler et al., Arch. Phys. Med. Rehabil. 1996; 77:461–466. Once clinical trials utilizing programmable infusion pump systems to intrathecally deliver baclofen for the management of dystonia/spasticity in traumatic brain injury were finally initiated, the results were favorable. Meythaler et al., J. NeuroSurgery 1997; 87:415–9; Akman et al., Paraplegia 1993; 31:516–20. However, not all patients have had a significant sustained response with intrathecally administered baclofen (Meythaler et al., Arch. Phys. Med. Rehabil. 1999; 80:13–9), which may be related to its effect only on GABA-B receptors.
Gamma-aminobutyramide appears to bind to both GABA-A and B receptors and it is an excellent candidate for use intrathecally as it is soluble in water and relatively stable for long periods of time. It is able to penetrate from the CNS into the central nervous system. Both the temporal horns and the frontal lobes of the brain are contiguous to the cerebral ventricles which contain CSF. 70% of all seizures are found to be originating in these areas by EEG monitoring. Consequently, intraventricular delivery of gamma-aminobutyramide should be useful in alleviating seizures.
Accordingly, the use of gamma-amninobutyramide, a solubility product of progabide, which is an agonist of both GABA-B receptors and GABA-A receptors, for the treatment of dystonia/spasticity in traumatically brain injured individuals is likely to have a more significant effect. This outcome is indicated by research which indicates that systemically delivered diazepam, a GABA-A receptor agonist, also has profound effects on dystonia and spasticity. Meythaler et al., Perspectives in Neurosurg. 1996; 7(2):99–107.
The blood brain barrier is effective in limiting delivery of GABA and gamma-aminobutyramide or (4-aminobutyramide) by systemic routes of delivery. Higher dosages are required to create a therapeutic effect because of poor penetration of the blood brain barrier, the higher dosages also increasing systemic toxicity.
In order to avoid system delivery difficulties, intrathecal and/or cerebral intraventricular administration of gamma-aminobutyramide directly into the cerebrospinal fluid is used to limit systemic toxicity due to the low doses delivered and to the small amount of the chemical or its metabolites that reach the liver from that reabsorbed from the reabsorbed CSF at the arachnoid villi. Additionally, it has been speculated that gamma-aminobutyramide could be useful to reduce spasticity, dystonia, and have effects as an anti-convulsant if its toxicity and systemic delivery issues could be solved. Kaplan et al., J. Med. Chem. 1980; 23:702–4.
Thus, there exists a need for an improved composition for systemic and/or intrathecal delivery of gamma-aminobutyramide.
SUMMARY OF THE INVENTION
A compound is provided that has the formula
NH 2 CH 2 CH 2 CH 2 C(O)N—R (I)
where R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine, blood brain barrier (BBB) peptide, TAT peptides, transferrin, glucosylamine, amino saccharin, lactylamine, leucine, tryptophan, amino glutamate and amino cholines. The compound traverses the blood brain barrier with greater efficiency than gamma-aminobutyramide thereby reducing side effects associated with systemic gamma-aminobutyric acid therapy. A process for forming a conjugate having the formula (I) illustratively includes reacting a butyric acid chloride or ester with a primary or secondary amine group of a transporter molecule able to traverse the blood brain barrier. The transporter molecule includes serotonin, dopamine, blood brain barrier (BBB) peptide, TAT peptide, transferrin, glucosylamine, amino saccharin, lactylamine, leucine, tryptophan, amino glutamate and amino cholines so as to form an amide bond. The amine of the transporter molecule reacts with the butyric acid chloride or ester to form an amide bond.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a method for treating neuronal conditions or disorders often associated with traumatic brain injury, including dystonia/spasticity, spastic disorders, convulsive disorders, tardive dyskinesia, pain or epilepsy by administration to a patient or subject having dystonia/spasticity, a spastic disorder, a convulsive disorder, pain or epilepsy a therapeutically effective amount of a gamma-aminobutyramide conjugate that is able to cross the blood-nerve barrier. Adjunct therapies for facilitating such transport are also provided.
The terms “patient” and “subject” are synonymous and mean all animals including humans. Examples of patients or subjects include humans, cows, dogs, cats, goats, sheep, and pigs.
The term “substituted” means that the base organic radical has one or more substituents.
The term “solubility products” means those compounds or compositions formed when a compound is disposed in a solvent.
Those skilled in the art are easily able to identify patients or subjects having dystonia/spasticity, spastic disorders, convulsive disorders, and epilepsy. For example, patients who have sustained traumatic brain injury induced dystonia/spasticity.
A therapeutically effective amount is defined as an amount of gamma-aminobutyramide conjugate that when administered to a patient or subject, ameliorates a symptom of the condition or disorder.
The compounds of the present invention can be administered to a patient either alone or as part of a pharmaceutical composition. The inventive compositions are suitable for administration to patients by a variety of routes including intrathecally, intraventricularly, intravenously, orally, parenterally, and mucosally.
Compositions suitable for delivery illustratively include physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and nonaqueous carriers; diluents; solvents; or vehicles include water, ethanol, polyols such as propylene glycol, polyethylene glycol, glycerol, and the like, suitable mixtures thereof; vegetable oils such as olive oil; and injectable organic esters such as ethyloleate. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants.
An inventive compound has the formula
NH 2 CH 2 CH 2 CH 2 C(O)N—R (I)
where R is a moiety capable of crossing the blood brain barrier and includes as a separate transporter molecule serotonin, blood brain barrier (BBB) peptide, dopamine, transferrin, TAT peptides, aminated glucose, aminated L-lactate, L-leucine, L-glutamate, aminated saccharin and aminated choline. An inventive compound being formed preferably through the reaction of an acid chloride with a primary or secondary amine in the presence of a tertiary amine present in a stoichiometric excess relative to the quantity of acid chloride. It is appreciated that gamma-aminobutyric acid is an inexpensive starting reagent for coupling by way of an amide linkage to a transporter moiety R. The small size of gamma-aminobutyramide precludes many of the transmembrane transport problems associated with larger molecules.
According to the present invention, a gamma-aminobutyramide conjugate compound is formed to a species known to traverse the blood brain barrier either through diffusion or a specific transporter. While the specific transport mechanism is unclear, owing to the small molecular weight and lack of steric hindrance associated with gamma-aminobutyramide, inhibitory affects on the transporter species associated with conjugation are limited.
In a preferred embodiment, an inventive conjugate compound includes a transporter moiety R having a privileged ability to pass the blood brain barrier and thereafter be cleaved from a gamma-aminobutyramide component to itself form an active therapeutic or neurochemistry equilibrium modifier. The ability to deliver as a conjugate gamma-aminobutyramide with a second neuroactive species provides a previously unavailable ability to moderate a neurological therapeutic effect. As neuroactive compounds are subject to complex feedback mechanisms, the successful transport of a compound across the blood brain barrier has a moderated therapeutic effect owing to neurochemistry equilibrium shifts in response to the compound traversing the barrier. An inventive conjugate provides gamma-aminobutyramide that upon cleavage from the transporter moiety R is in proximity to a second neurologically active species that has an agonistic, antagonistic, or independently operating neuroactive species. The aminobutyramide and moiety R after cleavage being subject to further enzymatic modification and/or efflux clearance. The simultaneous dosage of gamma-aminobutyramide and the neuroactive transporter moiety R upon cleavage assures the desired dose is present. It is appreciated that two or more inventive conjugates are amenable to simultaneous delivery in order to provide still more refined therapeutic affects.
An inventive conjugate compound is preferably formed through an amide linkage between a butyric acid chloride and a primary or secondary aminated blood brain barrier transporter compound. Aminated blood brain barrier transporter compounds operative herein illustratively include serotonin, blood brain barrier (BBB) peptide, membrane translocating protein, dopamine, transferrin, TAT peptides, aminated glucose, aminated L-lactate, L-leucine, L-glutamate, aminated saccharin and aminated choline. The aminated transporter compound is reacted with a butyric acid chloride in the presence of a tertiary amine chloride scavenger in order to form a butyramide having a nitrogen substituent that is able to cross the blood brain barrier. Tertiary amine chloride scavengers operative herein illustratively include pyridine, and trialkyl amines. Alternatively, a butyric acid ester such as a C 1 –C 6 alkyl ester illustratively including ethyl 4 t-BOC-amino-butyrate, and butyl ethyl 4 t-BOC-amino-butyrate.
Carbodiimides are zero length cross-linkers that mediate the formation of an amide or phosphoramidate linkage between a carboxylate and an amine, or a phosphate and an amine, respectively. Chu, B., Kramer, F. & Orgel, L. (1986), “Synthesis of an amplifiable reporter RNA for bioassays,” Nucleic Acids Research, 14, 5591–5603. Hoare, D. & Koshland, D. E. (1966) J. Am. Chem. Soc., 88, 2057. Carbodiimides react with carboxylic acids to form highly reactive O-acylisourea compounds that are very short lived but react with nucleophiles to form an amide bond. Dicyclohexylcarbodiimide (DCCD) is representative of a reactive carbodiimde. This reaction works effectively between pH 4.5 and 7.5. Molecules with a phosphate group such as the 5′ phosphate on oligonucleotides can also react with amine-containing groups by using the carbodiimide reaction.
Other precursors capable of reacting to form an amide bond are well known to the art. Methods for the preparation of an amide bond are described in Houben-Weyl, Methoden der organischen Chemie (Methods of Organic Chemistry ), Volume 15/2; Bodanszky et al.
It is appreciated that a butyric acid precursor to an inventive conjugate must include a protected gamma amino group or a moiety that subsequently is reacted to form an amino group yet is unreactive under conditions for the formation of the acid chloride or ester and the subsequent reaction thereof with the aminated transporter compound. Amine protective groups and the chemistry for the addition thereof to an amino butyric acid are provided in Protective Groups in Organic Synthesis by T. W. Greene and P. G. M. Wuts, John Wiley & Sons, 1999 and include the prototypical t-butoxy carbonyl (t-BOC). Alternatively, a moiety such as cyanoalkyl acid is provided as a precursor to form the acid chloride, perform the linkage with the transporter compound, and thereafter reduce the cyano moiety to form the terminal amino group of an inventive conjugate. It is appreciated that other moieties are readily converted to an amine group subsequent to the conjugation chemistry.
Optionally, a linker species is provided intermediate between the transporter moiety R and the aminobutyramide portion of an inventive conjugate. The linker in simplest form includes a moiety reactive with the carbonyl carbon of the butyryl precursor and a second moiety reactive with the transporter compound. Substituents extending from a linker are provided to modify the lipophilicity of an inventive conjugate, or tether a dye or spectroscopic marker. With the inclusion of a linker, care should be taken to limit both the molecular weight and the hydrophilicity of the linker in order to retain the ability to traverse the blood brain barrier. Typically, the linker has eight or less backbone carbon atoms. Preferably, the linker backbone is linked to the butyryl amido portion of an inventive conjugate through an oxygen atom or a carbon atom. The linker moiety reactive with the butyryl portion carbonyl carbon illustratively form an amide and an ester linkage. Transporter compound reactive moiety of the linker is dependent upon the transporter compound moiety to be bound thereto. Suitable chemistries for a variety of potential reaction moieties are found in Comprehensive Organic Transformations, R. C. Larock, John Wiley & Sons 1999.
It is appreciated that a linker, when present, is the preferred site for the attachment of an additional species. A substituent is optionally provided pendent from the linker backbone. The substituent illustratively includes a radioactive atom, a magnetic spectroscopically active marker and an organic dye. A radioactive atom is alternatively operative as a marker in isotope studies such as positron emission tomography, single photon emission computer tomography, radiological studies and the like. Common radio-isotopes used in medical imaging illustratively include 123 I, 99m Tc, and other chelated radioisotopes as detailed in U.S. Pat. No. 6,241,963. Spectroscopically active markers include NMR/MRI active contrast enhancing moieties known to the art such as gadolinium, as detailed in Contrast Agents 1: Magnetic Resonance Imaging (Topics in Current Chemistry, 221) by Werner Krause, Springer Verlag, Berlin, Germany. Organic dyes, while recognized to have potentially distinct NMR/MRI signatures, are provided to yield an optically active spectroscopic signature suitable for biopsy, surgical identification, or preclinical studies of tissue treated by an inventive compound.
Compositions suitable for injection optionally include physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (propyleneglycol, polyethyleneglycol, glycerol, and the like), suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.
These compositions may also contain adjuvants such as preserving, wetting, emulsifying, and dispensing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example, sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.
Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is admixed with at least one inert customary excipient (or carrier) such as sodium citrate or dicalcium phosphate or (a) fillers or extenders, as for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders, as for example, carboxymethylcellulose, alignates, gelatin, polyvinylpyrrolidone, sucrose, and acacia, (c) humectants, as for example, glycerol, (d) disintegrating agents, as for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate, (e) solution retarders, as for example, paraffin, (f) absorption accelerators, as for example, quaternary ammonium compounds, (g) wetting agents, as for example, cetyl alcohol, and glycerol monostearate, (h) adsorbents, as for example, kaolin and bentonite, and (i) lubricants, as for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents.
Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethyleneglycols, and the like.
Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells, such as enteric coatings and others well known in the art. They may contain opacifying agents, and can also be of such composition that they release the active compound or compounds in a certain part of the intestinal tract in a delayed manner. Examples of embedding compositions which can be used are polymeric substances and waxes. The active compounds can also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients.
The enteric coating is typically a polymeric material. Preferred enteric coating materials have the characteristics of being bioerodible, gradually hydrolyzable and/or gradually water-soluble polymers. The amount of coating material applied to a solid dosage generally dictates the time interval between ingestion and drug release. A coating is applied with to a thickness such that the entire coating does not dissolve in the gastrointestinal fluids at pH below 5 associated with stomach acids, yet dissolves above pH 5 in the small intestine environment. It is expected that any anionic polymer exhibiting a pH-dependent solubility profile is readily used as an enteric coating in the practice of the present invention to achieve delivery of the active to the lower gastrointestinal tract. The selection of the specific enteric coating material depends on properties such as resistance to disintegration in the stomach; impermeability to gastric fluids and active agent diffusion while in the stomach; ability to dissapate at the target intestine site; physical and chemical stability during storage; non-toxicity; and ease of application.
Suitable enteric coating materials illustratively includecellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropylmethyl cellulose phthalate, hydroxypropyhnethyl cellulose succinate and carboxymethylcellulose sodium; acrylic acid polymers and copolymers, preferably formed from acrylic acid, methacrylic acid, methyl acrylate, ammonio methylacrylate, ethyl acrylate, methyl methacrylate and/or ethyl; vinyl polymers and copolymers such as polyvinyl pyrrolidone, polyvinyl acetate, polyvinylacetate phthalate, vinylacetate crotonic acid copolymer, and ethylene-vinyl acetate copolymers; shellac; and combinations thereof. A particularly preferred enteric coating material for use herein are those acrylic acid polymers and copolymers available under the tradename EUDRAGIT®, Roehm Pharma (Germany). The EUDRAGIT® series L, L-30D and S copolymers are most preferred since these are insoluble in stomach and dissolve in the intestine.
The enteric coating provides for controlled release of the active agent, such that release is accomplished at a predictable location in the lower intestinal tract below the point at which drug release would occur absent the enteric coating. The enteric coating also prevents exposure of the active agent and carrier to the epithelial and mucosal tissue of the buccal cavity, pharynx, esophagus, and stomach, and to the enzymes associated with these tissues. The enteric coating therefore helps to protect the active agent and a patient's internal tissue from any adverse event prior to drug release at the desired site of delivery. Furthermore, the coated solid dosages of the present invention allow optimization of drug absorption, active agent protection, and safety. Multiple enteric coatings targeted to release the active agent at various regions in the lower gastrointestinal tract would enable even more effective and sustained improved delivery throughout the lower gastrointestinal tract.
The enteric coating optionally contains a plasticizer to prevent the formation of pores and cracks that allow the penetration of the gastric fluids into the solid dosage. Suitable plasticizers illustratively include, triethyl citrate (Citroflex 2), triacetin (glyceryl triacetate), acetyl triethyl citrate (Citroflec A2), Carbowax 400 (polyethylene glycol 400), diethyl phthalate, tributyl citrate, acetylated monoglycerides, glycerol, fatty acid esters, propylene glycol, and dibutyl phthalate. In particular, a coating composed of an anionic carboxylic acrylic polymer typically contains approximately 10% to 25% by weight of a plasticizer, particularly dibutyl phthalate, polyethylene glycol, triethyl citrate and triacetin. The coating can also contain other coating excipients such as detackifiers, antifoaming agents, lubricants (e.g., magnesium stearate), and stabilizers (e.g., hydroxypropylcellulose, acids and bases) to solubilize or disperse the coating material, and to improve coating performance and the coated product.
The enteric coating is applied to a solid dosage using conventional coating methods and equipment. For example, an enteric coating can be applied to a solid dosage using a coating pan, an airless spray technique, fluidized bed coating equipment, or the like. Detailed information concerning materials, equipment and processes for preparing coated dosage forms may be found in Pharmaceutical Dosage Forms: Tablets, eds. Lieberman et al. (New York: Marcel Dekker, Inc., 1989), and in Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems, 6.sup.th Ed. (Media, Pa.: Williams & Wilkins, 1995).
Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizing agents and emulsifiers, as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl alcohol, benzyl benzoate, propyleneglycol, 1,3-butyleneglycol, dimethylformamide, oils, in particular, cottonseed oil, groundnut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethyleneglycols and fatty acid esters of sorbitan or mixtures of these substances, and the like.
Besides such inert diluents, the composition can also include adjuvants, such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.
Suspensions, in addition to the active compounds, may contain suspending agents, as for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances, and the like.
An inventive compound is also delivered in conjunction with an active therapeutic compound. The therapeutic compound illustratively being active as antibiotic, a gamma or beta radiation emitting species, an anti-inflammatory, an antitumoral, an antiviral, an antibody, a hormone, an enzyme, and antigenic peptide or protein.
The examples presented below are intended to illustrate particular embodiments of the invention and are not intended to limit the scope of the specification, including the claims.
EXAMPLES
Example 1
Preparation of 4-aminobutyramide of Serotonin
Oxalyl chloride (2 mmol, 1 mL from 2 M solution in CH 2 Cl 2 ) is added to t-butoxycarbonyl (t-Boc) amine protected 4-aminobutyric acid (1 mmol) in CH 2 Cl 2 (10 mL) at room temperature under N 2 . The resulting mixture is stirred for 1.5 hours and concentrated in vacuo at 30° C. to obtain a viscous oil which is dried in a vacuum for 15 minutes. The acid chloride obtained was dissolved in CH 2 Cl 2 (10 mL) and cooled to −10° C. and serotonin (1 mmol, 175 mg) in CH 2 Cl 2 (10 mL) is added, followed by triethylamine (3 mmol, 0.42 mL), under N 2 . The resulting solution is stirred at room temperature for 6 hours. The resulting solution is stirred for 3 hours in trifluoroacetic acid (1 M) to remove the t-Boc group. Water (20 mL) is then added to the reaction mixture and the product is extracted into CH 2 Cl 2 (3×20 mL). CH 2 Cl 2 layers are combined, dried and concentrated in vacuo to obtain the inventive conjugate.
Example 2
Preparation of 4-aminobutyramide of N-glucosyl Amine
The preparation of Example 1 is repeated with the substitution of a molar stoichiometric equivalent N-glucosylamine for serotonin, to form the title conjugate.
Example 3
Preparation of 4-aminobutyramide of Dopamine
A mixture of ethyl t-butoxycarbonyl (t-Boc) amine protected 4-aminobutyrate (5 mmol) and dopamine (5 mmol) in 200 ml tetrahydrofuran are heated to 70° C. for 24 hours. The resulting dopaminyl-t-butoxycarbonyl (t-Boc) amine protected 4-aminobutyramide is collected as an oil and stirred for 3 hours in trifluoroacetic acid (1 M) to remove the t-Boc group. Water (20 mL) is then added to the reaction mixture and the product is extracted into THF (3×20 mL). THF layers are combined, dried and concentrated in vacuo to obtain the inventive conjugate.
Patent applications and publications mentioned in the specification are indicative of the levels of those skilled in the art to which the invention pertains. These applications and publications are incorporated herein by reference to the same extent as if each individual application or publication was specifically and individually incorporated herein by reference.
The foregoing description is illustrative of particular embodiments of the invention, but is not meant to be a limitation upon the practice thereof. The following claims, including all equivalents thereof, are intended to define the scope of the invention.
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A compound is provided that has the formula
NH 2 CH 2 CH 2 CH 2 C(O)N—R (I)
where R is a moiety capable of crossing the blood brain barrier and is as a free compound serotonin, dopamine blood brain barrier (BBB) peptide, membrane translocating protein, TAT peptides, bradykinin, beta-endorphin, bombesin, calcitonin, cholecystokinin, an enkephalin, dynorphin, insulin, gastrin, substance P, neurotensin, glucagon, secretin, somatostatin, motilin, vasopressin, oxytocin, prolactin, thyrotropin, an angiotensin, galanin, neuropeptide Y, thyrotropin-releasing hormone, gonadotropnin-releasing hormone, growth hormone-releasing hormone, luteinizing hormone, vasoactive intestinal peptidetransferrin, glucosylamnine, amino saccharin, lactylamine, leucine, tryptophan, glutamate and amino cholines.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The field of the invention is that of exercising apparatus and/or weight lifting devices. The invention is more particularly concerned with apparatus of this type which is portable and which is adapted for use in the home.
2. Description of the Prior Art
Types of exercising apparatus are shown in prior art patents including U.S. Pat. Nos. 1,646,818; 2,632,645; 2,648,540; 3,614,097; 3,815,903; and 3,874,657. Apparatus that is less related is shown in prior art patents including U.S. Pat. Nos. 3,207,511; 3,346,256; 3,709,167; 3,741,538 and 3,850,431. The types of apparatus in the first group of patents are relatively complex and lack the desired degree of portability. Additionally, in general, these devices or systems are lacking in the desired degree of versatility as respects capability to allow the user to perform desired different types of exercises. Typically, in these known types of apparatus, there are used two sets of weights and their correspondingly duplicate sets of pulleys and line systems whereby the weights are raised and lowered by manipulation of the hands and arms of the user. The herein invention is calculated to overcome these particular deficiencies as outlined, and to provide improvements as outlined in the detailed description hereinafter.
SUMMARY OF THE INVENTION
In a preferred embodiment of the invention as described in detail hereinafter, it takes the form of a portable frame or scaffold. The frame has upright side members upstanding from supporting members that can rest on the floor. At the upper ends of the uprights are transverse members connected between the uprights. A weight-holding cage is provided and is positionable between the side uprights. A system of pulleys and lines is provided. This system includes pulleys mounted at the bottom of the frame structure outside of the uprights and a group of pulleys carried by one of the transverse members at the top. Flexible lines can pass over the bottom pulleys and over the top pulleys carried by the transverse member at the top, and the lines then passing over the pulley on a cage which carries the weights. The user can take a position adjacent to the frame structure to grasp grips at the ends of the lines, and then by manipulation of the lines, the cage carrying the weights can be raised and lowered as desired. With this design and arrangement, only a single weight assembly is required rather than duplicate sets of weights.
The apparatus offers unusual versatility in the manner of its utilization and the different types of exercises that can be performed with it. The ends of the lines can be attached either to hand grips or an elongated bar. The apparatus can be used with the lines passing over only the upper pulleys and then to the pulley on the weight cage or, on the other hand, the lines can be arranged to pass over the pulleys at the bottom of the frame structure. The pulleys at the bottom are in blocks having a swivel mounting and the pulley blocks at the top are hinged. Using the pulleys at the bottom accommodates the apparatus to exercising from positions on or near the floor, the swivel mountings of the blocks accommodating pulls on the lines from various directions depending on the position taken by the user. The hinged mounting of pulley blocks at the top allows them to swing and to accommodate various directions of pull on the lines passing over these pulleys.
The weight carrying cage can be moved away from its position between the side uprights and the user can take a position directly between the uprights as desired for purposes of performing exercises such as weight-lifting, using barbells and the like. A barbell is supportable on moveable hooks and can be supported by way of holes provided in the vertical side uprights.
In the light of the foregoing, the primary object of the invention is to provide an improved, simplified, and portable exercising machine or apparatus adapted for home use.
A further object is to provide apparatus as described, which is of simplified construction, but possesses great versatility from the standpoint of the types of exercises that can be performed with it.
A further object is to provide apparatus as described having a frame with upright side members and having a single cage for holding weights along with a system of pulleys and lines with hand grips or a hand bar at the ends so that the user can manipulate the lines, and raise and lower the single weight-supporting cage.
A further object is to provide apparatus as described having the capability that the weight-supporting cage can be moved from its normal position with the user taking a position between the vertical uprights for purposes of performing other types of exercises.
Further objects and additional advantages of the invention will become apparent from the following detailed description and annexed drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an isometric view of preferred form of the apparatus of the invention illustrating one mode of utilization;
FIGS. 2, 3, 4 and 5 are sectional views taken respectively along the lines 2--2, 3--3, 4--4 and 5--5 of FIG. 1;
FIG. 6 is a rear view of the apparatus of FIG. 1;
FIG. 7 is a sectional view taken along the line 7--7 of FIG. 6;
FIG. 8 is a detail view of a snap-hook type of attachment for attaching cables to hand grips or a hand bar;
FIG. 9 is a detail view of a hand bar with metal eyes for securement of snap hooks;
FIG. 10 is a perspective view similar to FIG. 1 showing a modified manner of utilization of the invention;
FIG. 10A is a detail view illustrating a variation in the utilization of the form of the invention of FIG. 10;
FIG. 11 is an illustrative view of another form of the invention or manner of utilization thereof;
FIG. 12 is a partial view illustrating another form of the invention or manner of utilization thereof;
FIG. 12A is a view illustrating another manner of utilization of a form of the invention shown in FIG. 12.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now in more detail to FIGS. 1-7 of the drawings, there is shown an upright frame or scaffold construction supported on a rectangular base formed of front and back members 10 and 11 and side members 12 and 13. The front member 10 is a thicker member and is secured at its ends to the ends of side members 12 and 13 by bolts or other means. The back members 11 can be secured to the side members 12 and 13 by any suitable means. These members may be made of any suitable material. The base may rest on the floor of a home or the like. Upstanding from the base are upright members 14 and 16, each provided with spaced holes as shown at 17 to receive removable bars as shown at 19. Hooks as shown at 21 are provided for supporting barbells or the like. At the lower ends of these members are channel members 18 and 20 which are secured to the uprights and which provide for suitable securement to and support from the base.
Similar uprights and channel members are provided upstanding from the base and these members are identified by corresponding reference numerals primed.
The lower ends of the uprights 14 and 14' are secured to the channel members 18 and 20 by wing nuts as shown to provide for easy disassembly or demountability. Channel members 20 and 20' may be secured to the base member 12 by welding as illustrated in FIG. 2 and the member 12 may be a channel member.
Extending between the upper ends of the upright members 14 and 14' is a brace member 26 and between the upper ends of the uprights 16 and 16' is a similar member 26'. At the upper ends of all of the uprights are similar channel members corresponding to the previously described channel members 18-20 to which the uprights are similarly secured by wind nuts. Numeral 27 designates a removable front brace member extending between members 14' and 16' and secured by wing nuts.
Extending transversely between the side uprights at the top are transverse members. One of these is designted at 32 extending between the uprights 14 and 16. Numeral 34 designates a second transverse member extending between the uprights 14' and 16', this member being longer, its ends extending beyond the uprights 14' and 16' as shown. This member will be referred to again presently.
Extending outwardly laterally from the base member 12 is a short support member 40 which supports pulley block 41 and a pulley 42. Pulley block or housing 41 is secured to the support member 40 by a bolt 43 as shown for swivelling movement. At the opposite side of the frame structure is a similar support member 40', pulley block 41' and pulley 42', the pulley block or housing being secured to the member 40' by a bolt 43'. See FIG. 2.
Supported at the outer end of the upper transverse member 34 is a pulley block 44 and pulley 45 and at the opposite end of the member 34 is a corresponding pulley block 44' supporting pulley 45'. The pulley block 44 and pulley 45 are shown in detail in FIG. 4. Pulley block 44 is attached to the member 34 by a hinge 47 so that it can swing outwardly in a manner illustrated in FIG. 1 and pulley block 44' is similarly mounted by way of a hinge.
With respect to the pulley blocks 41 and 41', the bolts 43 and 43' provide for a swivel mounting of these blocks as will be described more in detail presently. FIG. 4 is a cross-sectional view which illustrates the mounting of pulley block 44 and pulley 45 from the transverse member 34.
Supported beneath an intermediate part of the member 34 are two similar hinged pulley blocks 48 and 50 having pulleys in them. All of the pulley blocks 44, 44', 48 and 59 are hinged to the member 34.
Numeral 60 designates a cage or frame enclosure for purposes of supporting weights of conventional type as illustrated in FIGS. 1, 5, 6, 10 and 11. Cage 60 has a circular base as designated at 62. It is illustrated in more detail in FIG. 5. It has an upright rod 64 upon which circular weights having a center opening can be mounted as shown at 65. The cage has two upright members 66 and 66' with a transverse member 67 extending between the upright members. The member 67 supports a pulley block 68 supporting a pulley 69. The pulley block 68 is open as may be seen at 71 to allow a cable to be placed over and removed from the pulley. See FIG. 5.
Numeral 70 designates a flexible line, cable or rope that is reeved over the pulleys as illustrated in FIGS. 1-6 and FIGS. 10-11. At the ends of the line are the hand grips 70 and 72' which can be grasped by the user. As may be seen, the line or lines can pass over the pulleys 42 and 42' and can pass over the pulleys in blocks 44 and 44' and 48 and 50 after which the line can pass over the pulley 69 in block 68.
FIGS. 6 and 12 illustrate an arrangements wherein the line or cable passes over the pulleys in blocks 41 and 41'. The ways in which the apparatus can be utilized will be described in more detail presently.
The hand grips 72 and 72' have eye members 73 and 73', part of the hand grip 72 shown in more detail in FIG. 8 having the eye 73. Preferably, at the ends of the cable 70 there are provided snaps such as shown at 74 in FIG. 8. The snap itself is of conventional construction having a thumb operator 75 and being secured by a loop at the end of the cable 70. The snaps can be engaged with the eyes 73 and 73' or disengaged thereform. As an alternative to the hand grips 72 and 72', a hand bar 77 may be utilized with the cable snapped to eyes at the ends of the hand bar, the eyes being designated at 79 and 79' with an additional eye 79" at the midpoint of the bar. The use of the bar will be referred to again presently. FIGS. 1-6 represent what is presently considered the best mode of practicing the invention.
One manner of utilization of the apparatus is illustrated in FIG. 1. The user is shown reclining on his back on the rest stand 84 which may be of conventional construction. The rest stand is of tubular construction having parallel tubular horizontal members 86 and 86', the ends of which are curved as shown forming legs. The stand is provided with a seat designated by the numeral 88 and which has a back part 89. The stand has two tubular uprights 90 and 90' which have transverse holes through them, the uprights being secured to a point on the frame members 86 and 86'. At the upper ends of the uprights 90 and 91 are arcuate members as shown at 92.
In FIG. 1, the cable is shown not passing over the pulleys 42 and 42', but just over the upper pulleys at the top of the frame. By manipulating the grips to pull on the lines, force is applied to raise and lower the cage 60 carrying the weights. The user can exert pull on the lines directly away from the frame or in other directions since the pulley blocks 44 and 44' are hinged as described to accommodate the lines passing away from the pulleys in various directions. The same pulling force need not be exerted on both lines.
FIGS. 6 and 12 illustrate another manner of utilization of the invention. In these figures, the cable 70 is reeved over the pulleys in the blocks 41 and 41' so as to particularly accommodate a user in a position on the floor such as shown in FIG. 12. Either the hand grips at the ends of the cable can be used or the bar as shown in FIG. 9. The user can pull on the cables in various directions which are accommodated by the fact that the pulley blocks 41 and 41' have swivel mountings.
FIG. 12A shows a variation of the manner of usage of FIG. 12 utilizing the rest or support stand 84 in the manner illustrated. The user is kneeling next to the stand with the bar 77 over his head in which position pulling movements can be exerted on the bar 77 along with upward and downward movements of it.
FIG. 10 shows another manner of utilization of the invention. In this case, the hand grips are unsnapped from the ends of the line or cable which are snapped to the eyes 79 and 79' at the ends of the hand bar 77. The cable arrangement is otherwise like that of FIG. 1. Various exercises can be performed as illustrated in FIG. 10 such as by pulling down or up on the bar or away from the stand or frame in various directions. FIG. 10A shows a variation of the exercises wherein the user stands between the stand or frame and the bar 77 allowing another range of exercises including ones that involve pushing the bar away from the stand.
FIG. 11 illustrates another manner of utilization of the invention. In this form of the invention, one of the snaps 74 is not connected to either a hand grip or the hand bar and is merely held against the pulley block 44 as shown. The cable 70 is attached to the center eye 79" on the bar 77 and the user takes a position at one side of the frame or stand as shown in FIG. 11. The user could, of course, be either in the position shown facing the stand or facing away from it with his hands gripping opposite ends of the hand bar 77. In this way, the pull on one end of the cable 70 serves to lift the weight cage 60. Various types of exercising motions and maneuvers are possible in this situation.
The nature and versatility of the apparatus can be appreciated from the foregoing. Only a single assembly of weights is needed, the weights being carried by the cage 60. The user can assume many exercising positions either sitting, reclining, kneeling, standing up or otherwise or grasping the grips 72 and 72' or the hand bar 77. As described, the user can take positions in front of the stand or frame or at one side of it, or others.
The cage 60 can, of course, be moved from its position between the uprights and the user can, if desired, take a position directly between the uprights for purposes of exercising. In such a position, the user may manipulate a barbell assembly which normally can be supported by the J-hooks previously described.
From the foregoing, those skilled in the art will readily understand the nature and utilization of the invention and the manner in which it achieves and realizes the objects as set forth in the foregoing.
The foregoing disclosure is representative of preferred forms of the invention and is to be interpreted in an illustrative rather than a limiting sense, the invention to be accorded the full scope of the claims appended hereto.
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A portable exercising device of simplified design and construction which enables a user to perform a number of different types of exercises. An upright frame or scaffold is provided. A cage or frame for supporting weights is positionable between uprights at the sides of the frame or scaffold. A system of pulleys and lines is provided with detachable hand grips or a bar at the ends of the lines so that a user in various positions holding the hand grips or bar can pull on the lines to raise and lower the cage holding the weights. The user may work between the uprights at the sides of the frame to perform uplifting exercises using barbells and the like. The system of pulleys includes pulley blocks and pulleys at the lower part of the frame and pulley blocks and pulleys at the upper part, the lower ones being swivel mounted and the upper ones being hinged. Alternatively, the lines can pass or not pass over the lower pulleys, the device thereby accommodating many different manners or modes of utilization.
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FIELD OF THE INVENTION
The instant invention relates generally to nickel hydroxide materials for the positive electrode of an alkaline electrochemical cell, and specifically to structurally modified nickel hydroxide materials.
BACKGROUND OF THE INVENTION
In rechargeable alkaline electrochemical cell, weight and portability are important considerations. It is also advantageous for rechargeable alkaline batteries to have long operating lives without the necessity of periodic maintenance. Rechargeable alkaline electrochemical cells are used in numerous consumer devices such as calculators, portable radios, and cellular phones. They are often configured into a sealed power pack that is designed as an integral part of a specific device. Rechargeable alkaline electrochemical cells can also be configured as larger "cell packs" or "battery packs" that can be used, for example, in industrial, aerospace, and electronics.
Examples of alkaline electrochemical cells are nickel cadmium cells (Ni--Cd) and nickel-metal hydride cells (Ni--MH). Ni--MH cells use a negative electrode having a metal hydride active material capable of the reversible electrochemical storage of hydrogen. Ni--MH cells typically use a positive electrode having nickel hydroxide as the active material. The negative and positive electrodes are spaced apart in an alkaline electrolyte. Upon application of an electrical potential across a Ni--MH cell, the metal hydride material of the negative electrode is charged by the electrochemical absorption of hydrogen and the electrochemical discharge of a hydroxyl ion, as shown in equation (1): ##EQU1## The negative electrode reactions are reversible. Upon discharge, the stored hydrogen is released to form a water molecule and release an electron.
Initially Ovshinsky and his teams focused on metal hydride alloys that form the negative electrode. As a result of their efforts, they were able to greatly increase the reversible hydrogen storage characteristics required for efficient and economical battery applications, and produce batteries capable of high density energy storage, efficient reversibility, high electrical efficiency, efficient bulk hydrogen storage without structural changes or poisoning, long cycle life, and repeated deep discharge. The improved characteristics of these "Ovonic" alloys, as they are now called, results from tailoring the local chemical order and hence the local structural order by the incorporation of selected modifier elements into a host matrix. Disordered metal hydride alloys have a substantially increased density of catalytically active sites and storage sites compared to single or multi-phase crystalline materials. These additional sites are responsible for improved efficiency of electrochemical charging/discharging and an increase in electrical energy storage capacity. The nature and number of storage sites can even be designed independently of the catalytically active sites. More specifically, these alloys are tailored to allow bulk storage of the dissociated hydrogen atoms at bonding strengths within the range of reversibility suitable for use in secondary battery applications.
Some extremely efficient electrochemical hydrogen storage materials were formulated, based on the disordered materials described above. These are the Ti--V--Zr--Ni type active materials such as disclosed in U.S. Pat. No. 4,551,400 ("the '400 Patent") to Sapru, Hong, Fetcenko, and Venkatesan, the disclosure of which is incorporated by reference. These materials reversibly form hydrides in order to store hydrogen. All the materials used in the '400 Patent utilize a generic Ti--V--Ni composition, where at least Ti, V, and Ni are present and may be modified with Cr, Zr, and Al. The materials of the '400 Patent are multiphase materials, which may contain, but are not limited to, one or more phases with C 14 and C 15 type crystal structures.
Other Ti--V--Zr--Ni alloys are also used for rechargeable hydrogen storage negative electrodes. One such family of materials are those described in U.S. Pat. No. 4,728,586 ("the '586 Patent") to Venkatesan, Reichman, and Fetcenko, the disclosure of which is incorporated by reference. The '586 Patent describes a specific sub-class of these Ti--V--Ni--Zr alloys comprising Ti, V, Zr, Ni, and a fifth component, Cr. The '586 Patent, mentions the possibility of additives and modifiers beyond the Ti, V, Zr, Ni, and Cr components of the alloys, and generally discusses specific additives and modifiers, the amounts and interactions of these modifiers, and the particular benefits that could be expected from them.
In contrast to the Ovonic alloys described above, the older alloys were generally considered "ordered" materials that had different chemistry, microstructure, and electrochemical characteristics. The performance of the early ordered materials was poor, but in the early 1980's, as the degree of modification increased (that is as the number and amount of elemental modifiers increased), their performance began to improve significantly. This is due as much to the disorder contributed by the modifiers as it is to their electrical and chemical properties. This evolution of alloys from a specific class of "ordered" materials to the current multicomponent, multiphase "disordered" alloys is shown in the following patents: (i) U.S. Pat. No. 3,874,928; (ii) U.S. Pat. No. 4,214,043; (iii) U.S. Pat. No. 4,107,395; (iv) U.S. Pat. No. 4,107,405; (v) U.S. Pat. No. 4,112,199; (vi) U.S. Pat. No. 4,125,688 (vii) U.S. Pat. No. 4,214,043; (viii) U.S. Pat. No. 4,216,274; (ix) U.S. Pat. No. 4,487,817; (x) U.S. Pat. No. 4,605,603; (xii) U.S. Pat. No. 4,696,873; and (xiii) U.S. Pat. No. 4,699,856. (These references are discussed extensively in U.S. Pat. No. 5,096,667 and this discussion is specifically incorporated by reference). Ni--MH materials are also discussed in detail in U.S. Pat. No. 5,277,999 to Ovshinsky, et al., the contents of which are incorporated by reference.
Nickel hydroxide has been used for many years as an active electrode material for the positive electrode of alkaline electrochemical cells. The reactions that take place at the nickel hydroxide positive electrode of a Ni--MH electrochemical cell are shown in equation (2): ##EQU2##
The positive electrodes are typically pasted nickel electrodes which consist of nickel hydroxide particles in contact with a conductive substrate. The conductive substrate is typically a porous foam comprising nickel or a nickel alloy. A nickel hydroxide positive electrode ideally possesses the attributes of: 1) high discharge capacity; 2) high charge acceptance and utilization; 3) high electrical conductivity; and, 4) long cycle life.
Conventionally, the nickel hydroxide electrode reaction has been considered to be a one electron process involving oxidation of divalent nickel hydroxide to trivalent nickel oxyhydroxide on charge and subsequent discharge of trivalent nickel oxyhydroxide to divalent nickel hydroxide, as shown in equation (2). Recent evidence suggests that quadrivalent nickel is involved in the nickel hydroxide redox reaction; however, full utilization of quadrivalent nickel has never been achieved.
In practice, electrode capacity beyond the one-electron transfer theoretical capacity is not usually observed. One reason for this is incomplete utilization of the active material due to electronic isolation of oxidized material. Because reduced nickel hydroxide material has a high electronic resistance, the reduction of nickel hydroxide adjacent the current collector forms a less conductive surface that interferes with the subsequent reduction of oxidized active material that is farther away.
Ovshinsky and his teams have developed positive electrode materials that have demonstrated reliable transfer of more than one electron per nickel atom. Such materials are described in U.S. Pat. No. 5,344,728, U.S. Pat. No. 5,348,822, U.S. Pat. No. 5,569,563 and U.S. Pat. No. 5,567,549. The disclosures of U.S. Pat. Nos. 5,344,728, 5,348,822, 5,569,563 and 5,567,549 are incorporated by reference herein. Many of these materials involve gamma phase cycling. Nickel hydroxide material that cycles between the beta(II) nickel hydroxide and gamma nickel oxyhydroxide crystalline phases provides for greater electrode capacity.
However, due to the difference in the volumetric densities between beta(II) nickel hydroxide and gamma nickel oxyhyroxide material, there is expansion and contraction of the material during charge and discharge cycling which can sometimes lead to irreversible damage to the positive electrodes. The expansion and contraction can cause the positive electrodes to swell during charging. This can reduce the number of charge/discharge cycles that the electrochemical cell can withstand by causing mechanical failures of the cell.
There is a need for a structurally modified nickel hydroxide material having microstructural and/or macrostructural modifications which can provide for high discharge capacity and increased utilization. There is also need for a nickel hydroxide material which can cycle between the beta(II) and gamma crystalline phases without significant material degradation.
SUMMARY OF THE INVENTION
One objective of the present invention is a method of producing nickel hydroxide which can create structural modifications in the nickel hydroxide crystals and replicate these modifications during particle growth.
Another objective of the present invention is a structurally modified nickel hydroxide material having high discharge capacity and increased utilization.
Yet another objective of the present invention is a nickel hydroxide material which can cycle between the beta(II) and gamma crystalline structures without significant material degradation.
These and other objectives are also satisfied by a method for producing a structurally modified nickel hydroxide active material for the positive electrode of an alkaline electrochemical cell, the method comprising the steps of: combining a nickel ion solution, an ammonium hydroxide solution, and an alkali metal hydroxide solution, whereby a reaction mixture is formed; and cycling the supersaturation of the reaction mixture.
These and other objectives are satisfied by a structurally modified nickel hydroxide material for the positive electrode of an electrochemical cell, the material having a structurally modified nickel hydroxide material for the positive electrode of an alkaline electrochemical cell, the material having a pore volume greater than about 0.02 cm 3 /g.
These and other objectives are also satisfied by a structurally modified, gamma phase cycleable, nickel hydroxide material for the positive electrode of an electrochemical cell, the material having a macrostructure and a microstructure sufficient to substantially eliminate disintegration of said nickel hydroxide material during electrochemical cycling between gamma and beta crystalline structures.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the rates of nucleation and particle growth as a function of supersaturation.
DETAILED DESCRIPTION OF THE INVENTION
Disclosed herein is a method for producing a structurally modified nickel hydroxide material. Generally, the method comprises the steps of combining a nickel ion solution, an ammonium hydroxide solution, and an alkali metal hydroxide to form a reaction mixture; and cycling the supersaturation of the reaction mixture.
Nickel hydroxide material may be prepared by combining a nickel ion solution with an alkali metal hydroxide. The reaction between the nickel ion solution and the alkali metal hydroxide results in the precipitation of the nickel hydroxide. The nickel hydroxide precipitate may be isolated, washed and dried. The nickel ion solution may be a nickel salt solution. The nickel salt solution may be a nickel nitrate solution, a nickel sulfate solution, a nickel chloride solution, or mixtures thereof.
Preferably, nickel hydroxide material is prepared by combining the nickel ion solution with an ammonium hydroxide solution so that a nickel-ammonium complex is formed. When the nickel-ammonium complex reacts with the alkali metal hydroxide, a spherically-shaped nickel hydroxide precipitate is grown.
The reaction between the nickel ion solution, the alkali metal hydroxide, and the ammonium hydroxide solution may be carried out simultaneously in a single reactor vessel. Preferably, the nickel ion solution and the ammonium hydroxide solution are premixed together in a first reactor vessel to form the nickel-ammonium complex. The nickel-ammonium complex is then mixed with the alkali metal hydroxide in a second reactor vessel to form the reaction mixture having a nickel hydroxide precipitate. In general, the method of producing the nickel hydroxide is not limited to a specific number of reaction vessels.
The method of the present invention includes the step of cycling the supersaturation of the reaction mixture that was formed by combining the nickel ion solution, ammonium hydroxide solution, and the alkali metal hydroxide. Generally, a solution is "saturated" when it contains the maximum amount of solute permitted by its solubility at specified conditions. Saturation is an equilibrium condition. A solution is "supersaturated" when it contains a concentration of solute in excess of that found in a saturated solution.
The "supersaturation" of a solution is the difference between the concentration of solute in solution at any instant of time and the equilibrium concentration in a saturated solution of the same solute. Supersaturation is a nonequilibrium condition and leads to precipitation as the reaction mixture attempts to relieve itself toward the equilibrium condition of saturation. The "relative supersaturation" is defined herein as the supersaturation divided by the equilibrium concentration of the solute.
The supersaturation of the reaction mixture may be cycled in many different ways. The supersaturation can be varied by either changing the concentration of solute in solution at any instant of time or by changing the equilibrium concentration in a saturated solution of the same solute. Hence, the supersaturation may be cycled by altering the pH, temperature, and/or pressure of the reaction mixture. The supersaturation may also be cycled by altering the concentrations of the reagents of the reaction mixture or by altering the stirring rate of the reagents. It is noted that any means of cycling the supersaturation of the reaction mixture is within the spirit and scope of the present invention.
A preferred way of cycling the supersaturation is by cycling the pH of the mixture. The pH of the reaction mixture may be cycled by cycling the volumetric amount of the alkali metal hydroxide solution added to the mixture. This may be done by cycling the flow of alkali metal hydroxide solution into the reaction mixture. This changes the pH of the reaction mixture in a continuous, cyclic fashion, thereby cycling the supersaturation. As the volumetric amount of the alkali metal hydroxide solution is increased, the pH of the mixture increases, and as the volumetric amount of the sodium hydroxide solution is decreased, the pH of the mixture decreases.
While not wishing to be bound by theory, it is believed that cycling the supersaturation of the reaction mixture changes the relative rates of nucleation and particle growth of the nickel hydroxide precipitate. Nucleation is a process which leads to the smallest particles that are capable of spontaneous growth. These minimum sized particles are called nuclei. For nucleation to start, a minimum number of ions or molecules must collect together, thus producing the starting nuclei for the particles. Generally, the rate at which these nuclei form increases with an increase in supersaturation. It is believed that the rate of nucleation may increase exponentially with the supersaturation of the reaction mixture. Particle growth is the growth of the nuclei that are already present in the reaction mixture. It is believed that particle growth may be directly proportional to the supersaturation of the reaction mixture.
FIG. 1 is a graph schematically showing the rates of nucleation and particle growth as a function of supersaturation. As shown in the graph, nucleation increases exponentially with supersaturation while particle growth increases linearly with supersaturation. Referring to FIG. 1, it is seen that the degree of supersaturation affects the relative rates of the two processes. For example, when the degree of supersaturation is less than point "x", particle growth is the dominant process resulting in a precipitate characterized by a small number of larger particles. When the degree of supersaturation is greater than point "x", nucleation is the dominant process resulting in a large number of smaller particles. Hence, the nature of the precipitate can be controlled by controlling the degree of supersaturation.
As discussed above, a preferred way of cycling the supersaturation is to change the pH of the solution. Increasing the pH increases the supersaturation of the reaction mixture. At higher pH values, the nickel hydroxide precipitation is in the "nucleation regime" whereby the ratio of the nucleation rate to growth rate is high. In this regime precipitation predominately forms many small crystallite nuclei and little crystalline growth on the nuclei occurs. On the other hand, decreasing the pH decreases the supersaturation of the reaction mixture. At lower pH values, the precipitation is in the so called "growth" regime whereby the ratio of nucleation rate to particle growth rate is low. In this regime, few nuclei are formed, and precipitation predominately causes growth of the previously formed crystallite nuclei.
Hence, as the pH of the precipitation reaction mixture is cycled, cycling also occurs between the growth phase and nucleation phase of the reaction continuum causing continuous variation in the ratio of the nucleation rate relative to the growth rate of the forming nickel hydroxide particles. While not wishing to be bound by theory, it is believed that this continuous variation in the relative rates of nucleation and growth creates internal imperfection and disorder, and imparts the unique microstructure and macrostructure of the nickel hydroxide material of the present invention.
U.S. Pat. No. 5,788,943, the "943" Patent, discloses a method of forming a structurally modified nickel hydroxide material by introducing external ultrasonic energy into the reaction mixture. It is noted that the "943" Patent fails to teach or suggest a method of making a structurally modified nickel hydroxide material by cycling the supersaturation.
The method described above produces a structurally modified nickel hydroxide material. Preferably, the nickel hydroxide is in the form of substantially spherical particles having microstructural and macrostructural modifications. "Macrostructural modification" is defined as the modification of one or more of the "macrostructural parameters" of the material. The macroscopic parameters of the material include pore area, pore volume, pore diameter, pore shape, pore distribution, average particle size, average particle shape, particle size distribution, BET surface area, and tap density. "Microstructural modification" is defined as the modification of one or more of the microscopic parameters of the material. The microscopic parameters of the material include, but are not limited to crystallite size, crystallite shape, and crystal lattice as determined by x-ray diffraction data.
Specifically, the nickel hydroxide material produced by the method disclosed herein has an increased pore volume. The pore volume of the material is preferably greater than about 0.02 cm 3 /g, more preferably greater than about 0.025 cm 3 /g, and most preferably greater than about 0.03 cm 3 /g. The increased pore volume of the material may provide more space for individual crystallites to expand without coming into contact with other nickel hydroxide material. This also reduces internal particle stress and reduces or eliminates particle disintegration and/or destruction. The increased pore volume may also increase the electrolyte wetting of the nickel hydroxide particles, thereby increasing the utilization of the material.
It is noted that the tap density of the material is preferably greater than about 1.8 g/cc, and more preferably greater than about 1.9 g/cc.
The material may have a BET (Brunauer-Emmett-Teller) surface area which is preferably greater than about 14 m 2 /g, more preferably greater than about 17 m 2 /g, and most preferably greater than about 20 m 2 /g. The material may also have a pore area which is preferably greater than about 0.5 m 2 /g, more preferably greater than about 1.0 m 2 /g, and most preferably greater than about 1.5 m 2 /g.
A higher surface area material also results in a lower current density during charge/discharge cycling and greater charge acceptance. The material may have a specific capacity of at least 230 mAh/g. Further the material may have an electron transfer rate greater than about 1.0 electron per nickel atom.
The structurally modified material may have a smaller crystallite size than the prior art materials. The average crystallite size is preferably less than about 90 Angstroms.
The structural modifications of the nickel hydroxide material of the present invention may allow for expansion of the nickel hydroxide from the beta phase to the gamma phase with substantially no structural damage. The smaller crystallite size of the modified material may result in reduced and adsorbed crystallite expansion during gamma phase conversion. This reduces internal crystallite stress and fracturing, thereby increasing the flexibility of the crystallites and permit long term reversible beta phase nickel hydroxide to gamma phase nickel oxyhydroxide cycling. Materials having a larger average crystallite size will be more susceptible to crystallite destruction. It should be noted that the average crystallite size reported herein is in the <101> direction.
Chemical or compositional modifiers may be added to the structurally modified materials of the present invention. The nickel hydroxide material may contain one or more modifier elements selected from the group consisting of Al, Ba, Bi, Ca, Co, Cr, Cu, Fe, In, K, La, Li, Mg, Mn, Na, Nd, Pb, Pr, Ru, Sb, Sc, Se, Sn, Sr, Te, Ti, Y, Zn, and mixtures thereof. Useful combinations include nickel with Co, or Co and one or more of the other elements.
EXAMPLE
A nickel sulfate solution (about 10 wt %), a cobalt sulfate solution (about 8 wt %), and an ammonium hydroxide solution (about 29 wt %) are mixed in a first reaction vessel to form a nickel-ammonia complex having a pH of about 8.0. The nickel ammonium complex is then mixed with a sodium hydroxide solution in a second reaction vessel. The nickel ammonium complex is pumped into the second reactor vessel at a rate of about 76 ml per minute. The sodium hydroxide solution is pumped into the second reactor vessel on demand and the sodium hydroxide pump is turned on and off so that the pH of the sodium hydroxide solution cycles between about 12.3 and about 12.8. The reaction mixture is kept at a temperature of about 47° C. and stirred at a rate of about 760 rpm.
The nickel hydroxide material made by the method described above (i.e., cycling the pH of the reaction mixture) had the modified structural and performance characteristics shown in Table 1 below.
TABLE 1______________________________________Property/Powder with pH cycling______________________________________Crystallite Size (A) 80Tap Density (g/cc) 1.93BET Surface Area (m.sup.2 /g) 20.83Pore Volume (cm.sup.3 /g) 3.97 × 10.sup.-2Pore Area (m.sup.2 /g) 1.74Average Pore Radius (Å) 38Average Particle Size 11.8(μm)Paste Capacity (mAh/g) 235______________________________________
It is to be understood that the disclosure set forth herein is presented in the form of detailed embodiments described for the purpose of making a full and complete disclosure of the present invention, and that such details are not to be interpreted as limiting the true scope of this invention as set forth and defined in the appended claims.
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A method for producing a structurally modified nickel hydroxide active material for the positive electrode of an alkaline electrochemical cell. The method comprises the steps of combining a nickel ion solution, an ammonium hydroxide solution, and an alkali metal hydroxide solution to form a reaction mixture; and cycling the supersaturation of the reaction mixture.
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REFERENCE TO RELATED APPLICATIONS
This application claims the priority of United Kingdom Application No. 1211837.8, filed Jul. 4, 2012, the entire contents of which are incorporated herein by reference.
FIELD OF THE INVENTION
This invention relates to an attachment for a hand held appliance, in particular an attachment for a hairdryer and an appliance, particularly a hairdryer comprising such an attachment.
BACKGROUND OF THE INVENTION
Blowers and in particular hot air blowers are used for a variety of applications such as drying substances such as paint or hair and cleaning or stripping surface layers. Generally, a motor and fan are provided which draw fluid into a body; the fluid may be heated prior to exiting the body. The motor is susceptible to damage from foreign objects such as dirt or hair so conventionally a filter is provided at the fluid intake end of the blower. Conventionally such appliances are provided with a nozzle which can be attached and detached from the appliance and changes the shape and velocity of fluid flow that exits the appliance. Such nozzles can be used to focus the outflow of the appliance or to diffuse the outflow depending on the requirements of the user at that time.
SUMMARY OF THE INVENTION
According to a first aspect, the invention provides a hairdryer comprising a handle, a body comprising a fluid outlet and a primary fluid outlet, a fan unit for generating fluid flow through the hairdryer, the hairdryer comprising a fluid flow path extending from a fluid inlet through which a fluid flow enters the hairdryer to the fluid outlet, and a primary fluid flow path extending from a primary fluid inlet to the primary fluid outlet, a heater for heating the primary fluid flow drawn through the primary fluid inlet, and a nozzle attachable to the body, the nozzle comprising a nozzle fluid inlet for receiving the primary fluid flow from the primary fluid outlet, and a nozzle fluid outlet for emitting the primary fluid flow, and wherein the nozzle is configured to inhibit the emission of the fluid flow from the fluid outlet.
The hairdryer has a primary flow which is that processed by and drawn into the appliance by the fan unit and a fluid flow which is entrained by the primary, processed flow. Thus the fluid flow through the hairdryer is amplified by the entrained flow.
The primary fluid flow path starts at a primary fluid inlet into the hairdryer i.e. a primary fluid inlet through which a primary fluid flow enters the hairdryer.
Preferably, the nozzle is configured to inhibit the generation of the fluid flow.
It is preferred that the nozzle comprises means for inhibiting the flow of fluid along the fluid flow path to the fluid outlet.
Preferably, the means for inhibiting the flow of fluid along the flow path to the fluid outlet comprises a bather which is located within the fluid flow path when the nozzle is attached to the hairdryer.
It is preferred that the barrier is located at an end of the nozzle.
Preferably, the barrier is substantially orthogonal to the longitudinal axis of the nozzle. Alternatively, the barrier is inclined to the longitudinal axis of the nozzle.
It is preferred that the primary fluid outlet is configured to emit the primary fluid flow into the fluid flow path, and wherein the nozzle comprises a first end which is insertable into the fluid flow path through the fluid outlet, and a second end remote from the first end, and wherein the nozzle fluid inlet is located between the first end and the second end of the nozzle.
Preferably, wherein the nozzle fluid inlet comprises at least one aperture extending at least partially about the longitudinal axis of the nozzle. It is preferred that the nozzle fluid inlet comprises a plurality of apertures extending circumferentially about the longitudinal axis of the nozzle.
Preferably, the at least one aperture has a length extending in the direction of the longitudinal axis of the nozzle, and wherein the length of said at least one aperture varies about the longitudinal axis of the nozzle.
It is preferred that the nozzle comprises a side wall between the first end and the second end of the nozzle, and wherein a portion of the side wall which is located between the first end and the second end of the nozzle at least partially defines the nozzle fluid inlet.
Preferably, the side wall is tubular in shape. It is preferred that the nozzle fluid inlet is formed in the side wall.
Preferably, the side wall extends about an inner wall, and wherein the nozzle fluid inlet is located between the walls of the nozzle. It is preferred that the inner wall is tubular in shape.
Preferably, the inner wall extends from the first end to the second end. It is preferred that the second end of the nozzle comprises the nozzle fluid outlet.
It is preferred that the nozzle fluid outlet is located between the first end and the second end of the nozzle.
According to a second aspect, the invention provides a nozzle for a hairdryer comprising a handle, a body comprising a fluid outlet and a primary fluid outlet, a fan unit for generating fluid flow through the hairdryer, a fluid flow path extending from a fluid inlet through which a fluid flow enters the hairdryer to the fluid outlet, and a primary fluid flow path extending from a primary fluid inlet to the primary fluid outlet, and a heater for heating the primary fluid flow drawn through the primary fluid inlet, wherein the nozzle is attachable to the body, the nozzle comprising a nozzle fluid inlet for receiving the primary fluid flow from the primary fluid outlet, and a nozzle fluid outlet for emitting the primary fluid flow, and wherein the nozzle is configured to inhibit the emission of the fluid flow from the fluid outlet.
The primary fluid flow path starts at a primary fluid inlet into the hairdryer, i.e. a primary fluid inlet through which a primary fluid flow enters the hairdryer.
Preferably, the nozzle is configured to inhibit the generation of the fluid flow.
It is preferred that the nozzle comprises means for inhibiting the flow of fluid along the fluid flow path to the fluid outlet of the hairdryer.
Preferably, the means for inhibiting the flow of fluid along the flow path to the fluid outlet comprises a bather which is located within the fluid flow path when the nozzle is attached to the hairdryer.
It is preferred that the barrier is located at an end of the nozzle.
Preferably, the barrier is substantially orthogonal to the longitudinal axis of the nozzle.
Alternatively, the barrier is inclined to the longitudinal axis of the nozzle.
Preferably, the nozzle comprises a first end which is insertable into the fluid flow path through the fluid outlet, and a second end remote from the first end, and wherein the nozzle fluid inlet is located between the first end and the second end of the nozzle.
It is preferred that the nozzle fluid inlet comprises at least one aperture extending at least partially about the longitudinal axis of the nozzle.
Preferably, the nozzle fluid inlet comprises a plurality of apertures extending circumferentially about the longitudinal axis of the nozzle.
It is preferred that the at least one aperture has a length extending in the direction of the longitudinal axis of the nozzle, and wherein the length of said at least one aperture varies about the longitudinal axis of the nozzle.
Preferably, the nozzle comprises a side wall between the first end and the second end of the nozzle, and wherein a portion of the side wall which is located between the first end and the second end of the nozzle at least partially defines the nozzle fluid inlet.
It is preferred that the side wall is tubular in shape.
Preferably, the nozzle fluid inlet is formed in the side wall.
It is preferred that the side wall extends about an inner wall, and wherein the nozzle fluid inlet is located between the walls of the nozzle.
Preferably, the inner wall is tubular in shape. It is preferred that the inner wall extends from the first end to the second end.
It is preferred that the second end of the nozzle comprises the nozzle fluid outlet.
Preferably, the nozzle fluid outlet is located between the first end and the second end of the nozzle.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will now be described by way of example and with reference to the accompanying drawings, of which:
FIGS. 1 a 1 f show various representations of a single flow path nozzle according to the invention;
FIGS. 2 a to 2 c show various representations of a single flow path nozzle attached to a hairdryer;
FIGS. 3 a to 3 d show a nozzle with an end valve;
FIG. 4 a shows an alternate single flow path nozzle attached to a hairdryer;
FIGS. 4 b to 4 g show an alternate single flow path nozzle;
FIGS. 5 a to 5 e show a further single flow path nozzle;
FIGS. 6 a to 6 f show another single flow path nozzle with a hairdryer;
FIGS. 7 a to 7 c show a nozzle and hairdryer having two inlets into a single flow path;
FIGS. 8 a to 8 d show an alternate two outlet arrangement;
FIGS. 9 a to 9 d show a further nozzle and hairdryer combination;
FIGS. 10 a to 10 g show yet another single flow path nozzle and hairdryer;
FIGS. 10 h and 10 i show the hairdryer without a nozzle; and
FIGS. 10 j to 10 m show a further attachment with a hairdryer.
DETAILED DESCRIPTION OF THE INVENTION
FIGS. 1 a to 1 f show a nozzle 100 comprising a generally tubular body 110 with a longitudinal axis A-A extending along the length of the body, having a fluid inlet 120 through a wall 112 of the body 110 and a fluid outlet 130 downstream of the fluid inlet 120 . The fluid inlet 120 has a length that extends in the direction of the longitudinal axis A-A of the nozzle and is located between a first or upstream end 100 a and a second or downstream end 100 b of the nozzle 100 .
In this example, the fluid outlet 130 is slot shaped and the length of the slot B-B is greater than the diameter C-C of the body 110 . In this example, the fluid inlet 120 comprises a number of discrete apertures 120 a separated by reinforcing struts 120 b . The apertures 120 a extend circumferentially about the longitudinal axis of the nozzle 100 .
In use, fluid flows into the fluid inlet 120 along the length of the body 110 along fluid flow path 160 and out through the fluid outlet 130 . The upstream end 100 a of the nozzle 100 is closed by an end wall 140 thus fluid can only enter the nozzle 100 via the fluid inlet 120 when in use.
FIGS. 2 a to 2 c show the nozzle 100 attached to a hairdryer 200 . The nozzle 100 is inserted into the downstream end 200 b of the hairdryer until a stop 210 is reached. In this position, the fluid inlet 120 of the nozzle 100 is in fluid communication with a primary fluid outlet 230 of the hairdryer 200 . The nozzle is an attachment for adjusting at least one parameter of the fluid flow emitted from the hairdryer and the downstream end 100 b of the nozzle protrudes from the downstream end 200 b of the hairdryer 200 .
The hairdryer 200 has a handle 204 , 206 and a body 202 which comprises a duct 282 , 284 . A primary fluid flow path 260 starts at a primary inlet 220 which in this example is located at the upstream end 200 a of the hairdryer i.e. at the distal end of the hairdryer from the fluid outlet 200 b . Fluid is drawn into the primary fluid inlet 220 by a fan unit 250 , fluid flows along primary fluid flow path 260 located on the inside of the outer body 202 of the hairdryer between the outer body 202 and the duct 282 , along a first handle portion 204 to the fan unit 250 .
The fan unit 250 includes a fan and a motor. The fluid is drawn through the fan unit 250 , along a second handle portion 206 and returns to the body 202 of the hairdryer in an inner tier 260 a of the body. The inner tier 260 a of the body 202 is nested within the primary fluid flow path 260 between the primary fluid flow path 260 and the duct 282 and includes a heater 208 . The heater 208 is annular and heats the fluid that flows through the inner tier 260 a directly. Downstream of the heater 208 , fluid exits the primary fluid flow path at the primary outlet 230 .
With the nozzle 100 attached to the hairdryer 200 , the primary outlet 230 is in fluid communication with the fluid inlet 120 of the nozzle 100 . Fluid that flows out of the primary outlet 230 flows along the body 110 of the nozzle 100 to the nozzle outlet 130 .
The hairdryer 200 has a second fluid flow path 280 . This second fluid flow path 280 flows from a second inlet 270 along the length of the body 202 of the hairdryer through duct 282 to a second outlet 290 outlet where, when there is no nozzle attached to the hairdryer, fluid flowing through the second fluid flow path 280 mixes with the primary fluid at the primary fluid outlet 230 . This mixed flow continues along duct 284 to the fluid outlet 200 b of the hairdryer. The fluid that flows through the second fluid flow path 280 is not processed by the fan unit 250 ; it is entrained by the primary fluid flow through the primary fluid flow path 260 when the fan unit is switched on.
The second fluid flow path 280 can be considered to flow along a tube defined by an upstream duct 282 and a downstream duct 284 where the primary outlet 230 is an aperture in the tube between the ducts 282 and 284 . The nozzle is partially inserted into the tube defined by the ducts 284 , 282 . In this example the nozzle 100 is slidably inserted into hairdryer outlet 200 b along downstream duct 284 past the aperture or primary fluid outlet 230 into the upstream duct 282 . The nozzle 100 is retained in the duct 282 , 284 by friction. In this example, the friction is provided between stop 210 and the duct 284 of the hairdryer.
Nozzle 100 is a single flow path nozzle and only fluid that has been processed by the fan unit 250 from the primary fluid flow path 260 flows through the nozzle 100 . The end wall 140 of the nozzle 100 is a barrier that blocks the second fluid flow path 280 and thereby prevents entrainment into the second fluid flow path when the nozzle is properly attached to the hairdryer. The nozzle 100 prevents emission of the entrained fluid and inhibits the generation of the entrained fluid.
As an alternative, the nozzle could extend into downstream duct 284 of the hairdryer 200 but not as far as the primary fluid outlet 230 . In this example, fluid from the primary fluid flow path 260 would mix with entrained fluid from the second fluid flow path 280 at the primary fluid outlet 230 and the mixed flow would enter the nozzle at the upstream end of the nozzle and continue to the fluid outlet 130 of the nozzle producing a combined fluid flow at the nozzle outlet.
It is advantageous that the end wall 140 of the nozzle 100 comprises a valve. This assists if the nozzle 100 is inserted into the hairdryer whilst the hairdryer is switch on. The valve is designed to open and let the full fluid flow through it this is for example around 22 l/s.
Referring now to FIGS. 3 a to 3 d , the operation of a valve in the nozzle will now be described. When the nozzle 100 is initially inserted into the outlet end 200 b of a hairdryer 200 as is shown in FIG. 3 a , the valve 150 in the upstream end wall 140 of the nozzle 100 opens. The valve 150 is attached to a central strut 152 of the end wall 140 and when the force of the fluid flow is high enough the valve 150 folds into the nozzle 100 to make an opening 154 , for example an annular opening, in the end wall 140 of the nozzle 100 . The valve 150 is pushed downstream by the force of the fluid flowing into the nozzle 100 .
Once the inlet 120 is partially aligned with the primary outlet 230 of the hairdryer 200 , some of the primary flow will flow through the inlet 120 which results in a reduction in the pressure at the valve 150 . Once at least the majority of the primary flow goes through the inlet 120 , the valve 150 will shut as is shown in FIG. 3 c . When the valve 150 is shut the end wall 140 of the nozzle is blocked so fluid cannot flow through the second fluid flow path 280 . Thus the only flow is from the primary outlet 230 of primary fluid flow path 260 into the inlet 120 of the nozzle.
Nozzle 100 is a hot styling nozzle. Although around only half of the normal flow through the hairdryer will flow through the nozzle to the outlet 130 the velocity of the flow is increased by the shape of the nozzle so a user will feel a similar force to that of normal flow. Normal flow is the total flow through the hairdryer without an attachment i.e. the primary flow plus the second or entrained flow. The shape of the nozzle outlet 130 reduces the cross sectional area compared with the hairdryer outlet 200 b which increases the velocity of the flow.
Whilst the hairdryer shown has the primary fluid flow path flowing through the handles of the hairdryer, this is not required. The primary fluid flow path can alternatively flow from the primary inlet 220 along the body 202 through the heater to the primary fluid outlet 230 and thence into the nozzle.
FIGS. 6 a to 6 f show a nozzle 800 and a nozzle 800 attached to a hairdryer 200 . In this embodiment, components illustrated and described with respect to FIGS. 2 a to 2 c have like reference numbers. The nozzle is similar to nozzle 100 but instead of a valve 150 , this nozzle 800 is provided with a slanted upstream end 800 a and fluid inlet 820 i.e. the fluid inlet 820 has a length that extends in the direction of the longitudinal axis of the nozzle 800 and varies about the longitudinal axis of the nozzle. The fluid inlet 820 is defined by a side wall 822 of the body 810 of the nozzle 800 where the side wall 822 is substantially orthogonal to the wall 812 of the body and the longitudinal axis A-A of the nozzle 800 .
When the nozzle 800 is inserted into the outlet end 200 b of a hairdryer 200 , the fluid inlet 820 gradually aligns with the primary fluid outlet 230 of the hairdryer ( FIG. 6 f ). When the nozzle 800 is fully inserted as is shown in FIG. 11 d , the whole of the annular primary fluid outlet 230 is in fluid communication with the nozzle inlet 820 .
There will be an initial resistance to the insertion of the nozzle 800 when the hairdryer is switched on as there will be both primary and second fluid flowing through the hairdryer however, the entrainment effect will gradually reduce as the hairdryer outlet end 200 b is blocked by the slanted nozzle inlet end 800 a until the hairdryer outlet end 800 b is completely blocked. At this point, primary flow from the primary fluid outlet 230 that cannot enter the fluid inlet 820 is redirected down a second fluid flow path 280 towards the rear or upstream end 200 a of the hairdryer. So, when the nozzle is initially inserted the primary flow cannot exit the downstream end 800 b of the nozzle but can flow in a reverse direction along the second fluid flow path 280 . This feature provides protection from the heater overheating during the nozzle insertion process as there will always be some fluid flowing through the primary fluid flow path.
FIGS. 4 a to 4 g show an alternate single flow path nozzle 600 having a generally tubular body 610 , a first or upstream end 600 a and a second or downstream end 600 b . There is a fluid inlet 620 in an outer wall 612 of the body 610 between the first end 600 a and the second end 600 b of the nozzle 600 and a fluid outlet 630 downstream of the fluid inlet 620 . In this example, the fluid outlet 630 is ring shaped or annular and is formed by an inner wall 614 of the nozzle 600 and the outer wall 612 .
The fluid inlet 620 is an opening in the outer wall 612 of the nozzle and is defined by an aperture formed from a slanted edge 622 b of the outer wall and a curved side wall 622 provided at the upstream end of the fluid inlet which connects the outer wall 612 and the inner wall 614 . The slanted edge of the outer wall is slanted in the direction of fluid flow to reduce turbulence and pressure losses as the primary flow enters the nozzle.
The outer wall 612 surrounds inner wall 614 and together walls 612 , 614 define a fluid flow path 660 through the generally tubular body 610 from the inlet 620 to the outlet 630 . In the vicinity of the outlet 630 , the inner wall curves outwards 614 b and increases in diameter causing a reduction in the cross section of the fluid flow path at the outlet 630 . The inner wall 614 continues beyond the outlet 630 and the end of the outer wall 612 of the nozzle 600 to a downstream nozzle end 600 b . The inner wall 614 b is convex and is a Coanda surface i.e. it causes fluid that flows through the fluid flow path 660 to hug the surface of the inner wall 614 b as it curves forming an annular flow at the outlet 630 and downstream nozzle end 600 b . In addition the Coanda surface 614 is arranged so a primary fluid flow exiting the outlet 630 is amplified by the Coanda effect.
The hairdryer achieves the output and cooling effect described above with a nozzle which includes a Coanda surface to provide an amplifying region utilising the Coanda effect. A Coanda surface is a known type of surface over which fluid flow exiting an output orifice close to the surface exhibits the Coanda effect. The fluid tends to flow over the surface closely, almost ‘clinging to’ or ‘hugging’ the surface. The Coanda effect is already a proven, well documented method of entrainment whereby a primary air flow is directed over the Coanda surface. A description of the features of a Coanda surface, and the effect of fluid flow over a Coanda surface, can be found in articles such as Reba, Scientific American, Volume 214, June 1963 pages 84 to 92.
Advantageously, the assembly results in the entrainment of air surrounding the mouth of the nozzle such that the primary air flow is amplified by at least 15%, whilst a smooth overall output is maintained
By encouraging the fluid at the outlet 630 to flow along 616 the curved surface 614 b of the inner wall to the downstream nozzle end 600 b , fluid is entrained 618 from outside the hairdryer 200 ( FIG. 4 c ) by the Coanda effect. This action of entrainment increases the flow of air at the downstream nozzle end 600 b , thus the volume of fluid flowing at the downstream nozzle end 600 b is magnified by the entrainment above what is processed by the hairdryer 200 through a fan unit 250 and heater 208 .
When the nozzle 600 is attached to a hairdryer 200 as shown in FIG. 4 a , the fluid inlet 620 aligns with a primary fluid outlet 230 of the hairdryer. Hairdryer 200 has a second fluid flow path 280 through a central duct 282 but this is blocked by the nozzle 600 . In the example shown in FIG. 2 a , nozzle 100 blocked the second fluid flow path 280 at the upstream end 100 a of the nozzle. In this example, the nozzle 600 uses an upstream continuation of curved wall 614 b which curves inwards to form a rounded end 616 which blocks the second fluid flow path.
In order to seal the nozzle fluid flow path 660 with respect to the primary fluid outlet 230 , the outer wall 612 of the nozzle is provided with a collar 612 a . The collar 612 a is upstanding from the outer wall 612 so has a larger diameter than the outer wall and is designed to fit with ducting 282 within the hairdryer 200 . The collar 612 a is upstream of the fluid inlet 620 of the nozzle 600 . A second collar 612 b is ideally also provided downstream of the fluid inlet 620 and prevents fluid from the primary outlet 230 of the hairdryer flowing between the outer wall 612 of the nozzle and the hairdryer outlet 200 b.
FIGS. 5 a to 5 e show a further single flow path nozzle 10 which is similar to the one described with respect to FIG. 8 . In this nozzle a fluid flow path 60 is provided from an inlet 20 to an outlet 30 . The inlet 20 is through an outer wall 12 of a generally tubular body 14 of the nozzle 10 between a first or upstream end 10 a and a second or downstream end 10 b of the nozzle 10 . The outlet 30 is a slit formed between the outer wall 12 and an inner wall 32 of the nozzle.
The inner wall 32 is convex and formed by a bung 34 which is located in the downstream end 12 b of the outer wall 12 . Fluid that flows through the fluid flow path 60 is funnelled by an upstream end 34 a of the bung 34 towards the outlet 30 . As the inner wall 32 is convex, fluid that flows out of the outlet 30 is drawn to the surface 32 by the Coanda effect and this entrains fluid 18 from the environment around the nozzle 10 .
The shape of the bung 34 at the downstream end 34 b is generally rectangular so the fluid exits the nozzle in a generally rectangular profile.
The rear or upstream end 10 a of the nozzle has a cone shaped bung 70 so when the nozzle 10 is used in conjunction with hairdryer 200 (not shown), fluid from the second fluid flow path 280 is blocked by the cone shaped bung 70 .
FIGS. 7 a to 7 c show a nozzle and hairdryer combination where the nozzle 1100 has a generally tubular body 1103 with a longitudinal axis D-D extending along the length of the body and having a first inlet 1102 and a second inlet 1104 into the fluid flow path 1106 of the nozzle 1100 . The hairdryer 1120 has a corresponding primary outlet 1122 and second primary outlet 1124 which provide fluid communication with the first inlet 1102 and the second inlet 1104 respectively. This arrangement means that the primary flow through the primary fluid flow path 1126 of the hairdryer has two outlet regions. The use of a nozzle 1100 on a hairdryer 1120 introduces a restriction to the flow through the hairdryer resulting in a drop in output by the hairdryer of up to around 4 l/s. By introducing a second primary outlet 1124 for the primary flow the drop in output is mitigated.
The second inlet 1104 is similar to first inlet 1102 in that is extends in the direction of the longitudinal axis of the nozzle and radially round through outer wall 1110 of the generally tubular body 1103 of the nozzle 1100 . The second inlet 1104 consists of a number of discrete apertures 1104 a separated by reinforcing struts 1104 b.
Referring to FIG. 7 a , which shows a portion of a hairdryer having a primary fluid outlet comprising first 1122 and second 1124 primary outlets when there is no nozzle attached to the hairdryer 1120 , the second primary outlet 1124 is closed as it is not required to increase flow through the primary fluid flow path 1126 of the hairdryer 1120 . A closure 1130 is provided which occludes, blocks, covers or restricts the second primary outlet 1124 . The closure 1130 is biased into the closed position by a spring 1132 , in this example, which pushes against the closure 1124 to occlude the second primary outlet 1124 . The first 1122 and second 1124 primary outlets both comprise apertures and are spaced apart along the longitudinal axis D-D of the nozzle 1100 .
Referring now to FIG. 7 c , the nozzle 1100 is provided with a lip 1108 which is upstanding from the generally tubular wall 1101 of the nozzle. The lip 1108 can be continuous or discontinuous around the perimeter of the generally tubular outer wall 1105 of the body 1103 of the nozzle 1100 and is of sufficient depth or height upstanding from the wall 1105 to firstly engage with the closure 1130 and secondly to allow the nozzle to be inserted up to the point of engagement of the lip 1108 with the closure 1130 without snagging of the nozzle 1100 .
The lip in this example is formed from an O-ring which is held in a recess formed in the body 1103 of the nozzle. Alternatives will be apparent to the skilled person and include, but are not limited to an integral moulded lip, a plastic/hard rubber ring, a living hinge, an overmoulded lip and a push fit arrangement.
The closure 1130 is ring shaped and has an S-shaped profile. Central to the ring is an aperture 1126 to enable fluid flowing through the primary fluid flow path 1126 of the hairdryer to exit the downstream end 1120 b of the hairdryer from the first primary fluid outlet 1122 of the hairdryer. A first end 1125 of the S-shaped profile of the closure 1130 engages with one end of spring 1132 and provides the means by which the closure 1130 is biased into an occluded or closed position. A second end 1127 of the S-shaped profile protrudes into the fluid flow path 1129 of the hairdryer between the primary outlet 1122 and the downstream end 1120 b of the hairdryer. This second end 1127 of the closure 1130 engages with the lip 1108 of the nozzle 1100 when the nozzle is inserted far enough into the downstream end 1120 b of the hairdryer 1120 (see FIG. 7 b ) and as the nozzle is inserted past the point of engagement, the closure 1130 is pushed against the action of the spring 1132 and slides, opening the second primary outlet 1124 to allow fluid flowing in the primary fluid flow path 1126 to exit via either the first primary outlet 1122 or the second primary outlet 1124 thus mitigating any restriction on fluid flow through the hairdryer from the use of a nozzle.
In order to prevent egress of fluid from the primary fluid flow path 1126 from the hairdryer outlet 1120 b around the outside of the nozzle 1100 . The outer wall 1103 is provided with an upstanding collar 1110 that extends about the outer wall 1103 and seals the nozzle with respect to the hairdryer outlet 1120 . The collar 1110 additionally provides a point of friction between the nozzle and the hairdryer that retains the nozzle within the hairdryer.
The nozzle 1100 has a downstream end 110 b where fluid is output through a nozzle outlet 1112 and an upstream end 1100 a . In one embodiment the upstream end 1100 b of the nozzle comprises an end wall 1114 . In this embodiment, the primary flow from the hairdryer is the only flow that is output from the nozzle outlet 1112 .
FIGS. 8 a to 8 d show a different arrangement. In this example, the second primary outlet 1174 from the primary fluid flow path 1176 is in an end wall 1160 of the hairdryer 1150 rather than through an internal wall.
Referring now to FIG. 8 a , the hairdryer has a generally tubular body 1152 having an inner wall 1154 a 1154 b and an outer or external wall 1156 . At the downstream end 1150 b of the hairdryer an end wall 1160 , 1180 is provided between the inner 1154 b and outer 1156 wall. The end wall is orthogonal to a longitudinal axis E-E of the body 1152 and includes a fixed portion 1160 and a moveable portion or closure 1180 . The closure 1180 is annular and is biased by a spring 1182 to be substantially flush with the fixed portion of the end wall 1160 . When a nozzle is inserted into the hairdryer 1150 , the closure 1180 is pushed against the spring 1182 , causing the spring to compress and open the second primary outlet 1174 . In this example, the closure 1180 is adjacent to the inner wall 1154 b of the hairdryer however the closure could be located anywhere between the inner and outer walls. In addition, the closure need not be continuous around the end wall.
Referring now to FIG. 8 d , the nozzle 1190 has a generally tubular body 1192 having an outer wall 1194 . A first inlet 1196 is provided in the outer wall 1194 between an upstream or first end 1190 a and a downstream or second end 1190 b of the nozzle but towards the upstream end 1190 a of the nozzle. This first inlet 1196 is in fluid communication with a first primary outlet 1172 of the hairdryer provided in the inner wall 1154 of the body of the hairdryer and a fluid flow path 1197 is provided through the nozzle from the first inlet 1196 through the body 1192 of the nozzle to a nozzle outlet 1198 at the downstream end 1190 b of the nozzle. The outer wall 1194 of the nozzle is designed to be insertable into the outlet end 1150 b of the hairdryer. At the downstream end 1194 b of the outer wall 1194 a hook shaped lip 1193 is provided. When the nozzle 1190 is inserted in the hairdryer, the hooked shaped lip 1193 covers the end of inner wall 1154 b of the hairdryer and engages with closure 1180 pushing it against the action of the spring 1182 . In order to provide a second fluid flow path 1184 from the second opening 1174 to the downstream end 1190 b of the nozzle, a collar 1195 is provided on the nozzle. When the nozzle is inserted into the hairdryer, the collar 1195 fits over the outer wall 1156 of the body 1152 of the hairdryer and forms together with the fixed portion of the end wall 1160 and the hook shaped lip 1193 a second fluid inlet 1184 for the nozzle which combines with fluid from the first inlet 1196 in the fluid flow path 1197 within the nozzle.
The nozzle 1190 is inserted as shown in FIGS. 8 b and 8 c ; the lip 1193 engages with the closure 1180 and forces the closure back against the action of the spring 1182 opening the second primary outlet 1174 .
FIGS. 9 a to 9 d show an alternate arrangement for mitigating flow restriction when a nozzle 1200 is used on a hairdryer 1252 . In this example, insertion of a nozzle 1200 results in the primary fluid outlet 1250 of the hairdryer 1252 increasing in size.
The nozzle 1200 has a generally tubular body 1202 with a longitudinal axis F-F extending along the length of the body 1202 . A fluid inlet 1208 comprising a number of apertures 1210 separated by struts 1212 has a length that extends in the direction of the longitudinal axis F-F of the nozzle 1200 and is located between a first or upstream end 1200 a and a second or downstream end 1200 b of the nozzle 1200 in an outer wall 1204 of the body 1202 .
The hairdryer 1252 has a generally tubular body having an inner wall 1254 a , 1254 b , an outer wall 1256 and a primary fluid flow path 1258 provided therebetween. The primary fluid flow path 1258 flows from a primary inlet 1220 to a primary outlet 1250 provided as an aperture between two sections of the inner wall 1254 a , 1254 b and then through a central bore 1260 in the body of the hairdryer 1252 to a hairdryer outlet 1262 .
The primary outlet 1250 is formed from a fixed surface 1270 attached to the downstream section of inner wall 1254 b and a moveable surface 1272 which is connected to an upstream section of the inner wall 1254 a . In order that the primary outlet 1250 can be opened, a moveable portion 1254 aa of the upstream inner wall 1254 a is slidably moveable against the direction of fluid flow at the primary fluid outlet 1250 towards the upstream end 1252 a of the hairdryer 1252 . The upstream section of the inner wall 1254 a and the moveable portion 1254 aa form a lap joint 1282 ( FIG. 14 d ) which is biased apart by a spring 1280 ( FIGS. 9 a and 9 b ). The moveable portion 1254 aa has an internal surface which describes a duct 1262 within the hairdryer and is provided with a rim or lip 1264 which is upstanding from the duct 1262 and extends radially into the duct 1262 . When a nozzle 1200 is inserted into the outlet 1262 of the hairdryer, the upstream end 1200 a of the outer wall 1204 of the nozzle engages with the rim or lip 1262 on the moveable portion 1254 aa and pushes the moveable portion 1254 aa against the biasing action of the spring 1280 so the moveable portion 1254 aa slides towards the upstream inner wall 1254 a and opens the primary fluid outlet 1250 ( FIGS. 9 c and 9 d ).
When the nozzle 1200 is subsequently removed, the moveable portion 1254 aa slides back towards the downstream end 1252 b of the hairdryer 1252 causing the primary outlet 1250 to reduce back to its' original size.
FIGS. 10 a , 10 b , 10 h to 10 k all show a hairdryer 670 having a primary fluid flow path 671 which is processed by a fan unit 672 and a heater 673 second fluid flow path 680 which comprises fluid that has been entrained into the hairdryer by the action of the fan unit 672 drawing fluid into the primary fluid flow path 671 .
Referring in particular to FIGS. 10 h and 10 i , a primary fluid flow is drawn into the primary fluid flow path 671 at a primary inlet 674 and flows along a first handle 676 though a fan unit 672 , along a second handle 677 through a heater 673 and out of a primary outlet 675 into a duct 678 of the hairdryer to the fluid outlet 679 . A second fluid flow path 680 is provided from a second inlet 681 at the upstream end 670 a of the hairdryer through the duct 678 to the hairdryer outlet 679 . Fluid is entrained into the second fluid flow path 680 by the action of the fan unit 672 drawing fluid into the primary inlet 674 to the primary outlet 675 and mixes or combines with the primary flow at the primary fluid outlet 675 . The fluid that flows through the duct 678 to the outlet 679 is a combined primary and entrained flow.
The primary fluid outlet 675 is relatively large and unrestricted. In order to encourage entrainment into the second fluid flow path 680 , an attachment 685 is provided. The attachment 685 ( FIGS. 10 l and 10 m ) is inserted into the hairdryer outlet 679 and comprises a generally tubular body 686 between a first or upstream end 685 a and a second or downstream end 685 b . In order to encourage entrainment by the Coanda effect, the attachment 685 is provided with a Coanda surface 687 at the upstream end 685 a . The Coanda surface 687 is in fluid communication with the primary fluid outlet 675 when the attachment is inserted in the hairdryer 670 ( FIGS. 10 j and 10 k ) and causes primary fluid to hug the Coanda surface 687 when the primary fluid flow exits the primary fluid outlet 675 into the nozzle fluid flow path 688 and to a nozzle outlet 689 . The downstream end 685 b of the attachment 685 is provided with an upstanding lip 690 which protrudes from the downstream end 670 b of the hairdryer and covers the downstream end 670 b of the hairdryer. The nozzle outlet 689 is circular and has a smaller diameter than the hairdryer outlet 679 .
Referring now to FIGS. 10 c to 10 g , a second attachment 850 is provided. This second attachment 850 is a hot styling nozzle and only provides an outlet for the primary flow from the hairdryer 670 .
The second attachment 850 has a generally tubular body 851 which defines a longitudinal axis G-G of the attachment from a first or upstream end 850 a to a second or downstream end 850 b . At the upstream end 850 a , an end wall 852 is provided which is designed to block the second fluid flow path 680 of the hairdryer 670 . A fluid inlet 853 is provided in the body 851 downstream of the end wall 852 and fluid can flow from the fluid inlet 853 along a fluid flow path 854 to a fluid outlet 855 at the downstream end 850 b of the nozzle. The nozzle 850 is designed to be partially insertable into hairdryer 670 such that the fluid inlet is in fluid communication with the primary fluid outlet 675 . The portion of the nozzle that is insertable is generally tubular and is provided with an upstanding lip of collar 856 around the body 850 which abuts the downstream end 670 b of the hairdryer when the attachment 850 is inserted properly. Downstream of the lip 856 , the change of the attachment changes from generally circular to generally rectangular to provide a focused flow from the nozzle outlet 855 .
When there is no nozzle of the first type of nozzle 685 attached to the hairdryer 670 , a primary fluid flow is augmented by an entrained flow through the second fluid flow path 680 and the total fluid output from the fluid outlet 679 is the combined value of the primary flow and the entrained flow. The second attachment 850 only allows primary flow from the hairdryer and blocks the entrained flow so, could suffer from a lower velocity of fluid output at the nozzle outlet 855 . However, this is mitigated as the upstream end 855 a of the nozzle 855 is designed to sit in the duct 678 of the hairdryer 670 so it does not restrict flow from the primary outlet 675 . The upstream end of the nozzle body 851 has a curved wall 857 so turbulence and pressure losses as a result of the use of the second attachment 850 are minimised. This second nozzle 850 has the effect of opening up the amp gap or the primary fluid outlet 675 .
The lip or collar 856 , 690 has the effect of not only informing the user that the nozzle or attachment 850 , 685 has been correctly inserted into the hairdryer outlet 679 but also provides a seal against fluid from the primary fluid outlet 675 exiting external to the nozzle or attachment 850 , 685 .
The nozzle is retained with respect to the hairdryer by one of a number of alternatives which include but are not limited to a felt seal, a bump stop, an O-ring, magnets, friction fit, a mechanical clip, snap fit or actuated snap fit.
The hairdryers are preferably provided with a filter 222 ( FIGS. 2 b and 2 c ) which covers at least the primary fluid flow inlet 220 of the hairdryer. The filter 222 is provided as is prevents ingress of dust, debris and hair into the primary fluid flow path upstream 260 of the fan unit 250 which includes a fan and a motor. These foreign objects could damage the motor and cause premature failure of the hairdryer. The filter 222 can cover the entire intake of the hairdryer i.e. both the primary fluid flow path 260 and the second fluid flow path 280 however this is not preferred as it interferes with a line of sight through the appliance. A line of sight through the appliance is restricted by the use of a nozzle on the appliance.
The invention has been described in detail with respect to a nozzle for a hairdryer and a hairdryer comprising a nozzle however, it is applicable to any appliance that draws in a fluid and directs the outflow of that fluid from the appliance.
The appliance can be used with or without a heater; the action of the outflow of fluid at high velocity has a drying effect.
The fluid that flows through the appliance is generally air, but may be a different combination of gases or gas and can include additives to improve performance of the appliance or the impact the appliance has on an object the output is directed at for example, hair and the styling of that hair.
The invention is not limited to the detailed description given above. Variations will be apparent to the person skilled in the art.
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A hairdryer includes a handle; a body comprising a fluid outlet and a primary fluid outlet; a fan unit for generating fluid flow through the hairdryer, the hairdryer comprising a fluid flow path extending from a fluid inlet through which a fluid flow enters the hairdryer to the fluid outlet, and a primary fluid flow path extending from a primary fluid inlet to the primary fluid outlet; a heater for heating the primary fluid flow drawn through the primary fluid inlet; and a nozzle attachable to the body, the nozzle comprising a nozzle fluid inlet for receiving the primary fluid flow from the primary fluid outlet, and a nozzle fluid outlet for emitting the primary fluid flow, and wherein the nozzle is configured to inhibit the emission of the fluid flow from the fluid outlet.
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CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Patent Application No. 60/894,990 filed Mar. 15, 2007, which is incorporated by reference herein in its entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Technical Field
[0003] This invention generally relates to elevator systems in general, and to flexible load-bearing members for supporting and propelling an elevator car relative to a drive sheave in particular.
[0004] 2. Background Information
[0005] There are several known types of elevator systems. Traction-based systems typically include an elevator car and a counterweight and load-bearing members that support and connect the car and counterweight. The car is moved between various floors because of friction/traction between the load-bearing members and a drive sheave.
[0006] Historically, elevator systems have used “ropes” to extend between an elevator car and a drive sheave, and in some applications to a counterweight as well. The term “rope” is a term of art that typically refers to a generally circular member formed from a plurality of wound strands. Steel ropes, which consist of a plurality of wound steel fibers, are subject to corrosion, very high pressure, excessive wear, and premature failures. Recently other load-bearing members have been utilized, such as coated steel belts and fiber ropes. Disadvantages associated with coated steel belts include manufacturing costs, inability to visually inspect, possible traction problems, and possible degradation of the coating. Fiber ropes have ride quality issues (lower stiffness resulting in higher elongation), difficult inspection methodologies, very high-pressure and high wear rates.
[0007] It would, therefore, be beneficial to be able to provide an elevator system with a load-bearing member having one or more of improved corrosion resistance, inspectability, traction, and manufacturability.
SUMMARY OF THE INVENTION
[0008] According to the present invention, a load-bearing member operable to be driven by a drive sheave in an elevator system is provided. The load-bearing member has a body defined by a thickness, a width that is greater than the thickness, and a length. The body comprises a single solid material that is uniform in the cross-section, and is sufficiently flexible to permit the member to wrap at least partially around the drive sheave of an elevator system.
[0009] According further to the present invention, an elevator system is provided. The elevator system includes a plurality of load-bearing members, a car, a counterweight and a drive sheave. Each load-bearing member has a body defined by a thickness, a width that is greater than the thickness, and a length. The body comprises a single solid material, and is uniform in the cross-section. The load-bearing members connect the car and counterweight to the drive sheave, and are wrapped at least partially around the drive sheave.
[0010] It is desirable to make elevator systems smaller and more reliable. The present invention facilitates making an elevator system size much smaller at a given system weight. All industrialized nations regulate elevator system design with specific strength and durability requirements. In particular, most countries specify that the ratio of the drive machine sheave diameter to the load-bearing member diameter/thickness (D/d) must be greater than or equal to 40:1. Hence, the rope/belt size necessary to support the load with an appropriate safety factor (e.g., ≧10) will dictate the drive sheave diameter. The drive sheave diameter, in turn, dictates the machine torque requirements and, therefore, the size of the driving motor. A large percentage of the cost of an elevator system is due to the size of the motor. The thin cross-section of the present invention load-bearing members permits the use of very small diameter drive sheaves, and related very small motors.
[0011] Because elevator systems typically operate with different weights attached to each end of the load-bearing members, there are different elongation characteristics between lightly loaded and heavily loaded sides. These differences, side to side, are accommodated as the load-bearing members pass over the driving sheave. There is also continual relative motion between the drive sheave and the load-bearing members, which is referred to as creep, and further relative motion caused by acceleration, deceleration, sudden stops, etc. The relative motion can cause wear on load-bearing members. To accommodate the relative motion, and thereby minimize the aforesaid wear, compliant, high friction coatings having a uniform thickness are applied to the grooves of the drive sheaves. An example of an acceptable high friction coating is castable polyurethane.
[0012] In most elevator systems, a plurality of load-bearing members is used. To keep the load-bearing members in alignment and in their correct groove positions, a positive crown (convex surface) can be utilized on each groove of the drive sheave. Each groove may have coated shoulders to prohibit contact between adjacent load-bearing members. Because of the need to control the elevator car even in the event of a fire, the drive sheave must possess adequate friction without the polyurethane coating. The groove surfaces can be roughened and hardened to provide the necessary friction and control of the car.
[0013] Another advantage of the present invention is that the load-bearing members can be made of corrosion resistant stainless steel that does not require periodic lubrication. Prior art steel wire ropes require lubrication. The ability of the present invention load-bearing members to operate without lubrication enables the present invention elevator systems to operate in a more environmentally favorable manner.
[0014] The exposed nature of the present invention load-bearing members facilitates periodic inspections. Coated steel belts and aramid fiber ropes include coatings that surround the strength members to retard abrasion and impart cohesion. These coatings create problems for periodic inspection and in some instances necessitate the use of monitoring equipment and specific inspection methodologies. In contrast, the present inventions load-bearing members are readily accessible for visual inspection and, if deemed necessary, can be inspected using dye penetrant inspection (DPI).
[0015] For those embodiments of the present invention that utilize stainless steel load-bearing members, after the useful life of the members is completed the stainless steel can be completely recycled. In contrast, oily steel ropes, coated steel belts, and coated fiber ropes have little or no recycle value and are typically discarded after their useful life is completed.
[0016] The foregoing and other objects, features and advantages of the present invention will become more apparent in light of the following drawings and detailed description of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 diagrammatically illustrates a typical 2:1 elevator system configuration.
[0018] FIG. 2 diagrammatically illustrates an alternative elevator system configuration.
[0019] FIG. 3 is a diagrammatic perspective view of a flexible load-bearing strip in accordance with the present invention.
[0020] FIG. 4 is a diagrammatic partial view of a crowned sheave with a coating or sleeve, and a load-bearing member engaged with the sheave.
[0021] FIG. 5 is a diagrammatic cross-sectional view of a load-bearing member, including arcuate longitudinal edge surfaces.
[0022] FIG. 6 diagrammatically illustrates a traction sheave embodiment in accordance with the present invention.
[0023] FIG. 7 is a data table of exemplary flexible load-bearing strips and associated sheave data.
DETAILED DESCRIPTION OF THE INVENTION
[0024] Now referring to FIG. 1 , an elevator system 10 includes an elevator car 14 and a counterweight 16 is diagrammatically shown within a hoistway 46 , connected to one another by one or more flexible load-bearing members 12 . The load-bearing members 12 are shown extending in a 2:1 roping configuration, wherein the members 12 pass over a drive sheave 18 , drop to the elevator car 14 or counterweight 16 , and subsequently wrap around another unpowered sheave(s) 15 attached to the respective car 14 or counterweight 16 before returning to an anchor position 44 at the top of the hoistway 46 . As will be detailed below, frictional engagement (i.e., traction) between the drive sheave 18 and load-bearing member 12 enables the drive sheave 18 to move the load-bearing member 12 and therefore the attached elevator car 14 and counterweight 16 .
[0025] In a 2:1 system, the grooves of the sheaves 15 , 18 are typically crowned for alignment purposes, as will be discussed below. The configuration of the sheaves 15 , 18 will subject the load-bearing members 12 to reverse curvatures when the load-bearing members 12 engage the crowned sheaves 15 , 18 . To prevent mis-tracking as the load-bearing members 12 enter a sheave 18 , it is known to use flat rollers 13 with low friction coating, which rollers 13 are positioned adjacent to the drive sheave 18 to reflatten the load-bearing members 12 . The grooves of the unpowered sheaves 13 within the 2:1 system are typically coated with a durable, low friction material to prevent/minimize tension imbalance between the flat load-bearing members 12 . Acceptable coating materials include polypropylene or polyethylene, or alternatively the entire sheave 13 can be made from high hardness Nylon with friction-reducing additives.
[0026] FIG. 2 diagrammatically illustrates another elevator system embodiment in which one or more load-bearing members 11 (e.g., a steel rope) extend between an elevator car 14 and a counterweight 16 , passing at least partially around one or more non-powered sheaves 42 located at the top of the hoistway. One or more load-bearing members 12 extend between the elevator car 14 and a counterweight 16 , wrapped at least partially around a powered traction sheave 18 located at or near the bottom of the hoistway 46 . Frictional engagement (i.e., traction) between the traction sheave 18 and load bearing member 12 enables the traction sheave 18 to move the load-bearing member 12 and therefore the attached elevator car 14 .
[0027] Now referring to FIG. 3 , the load-bearing member 12 utilized in the above-described elevator systems has a first contact surface 48 , a second contact surface 50 , and longitudinal edges 52 extending between the first and second contact surfaces 48 , 50 . The first and second contact surfaces 48 , 50 extend across the width 54 of the strip 12 and the longitudinal edges 52 extend across the thickness 56 of the strip 12 . The width 54 and thickness 56 of the strip 12 are disposed in a cross-sectional plane that is perpendicular to the length 58 of the strip 12 . The width 54 and thickness 56 are typically uniform through out substantially all of the length 58 of the strip 12 , with the specific width and thickness chosen to suit the application at hand; e.g., the width 54 and the thickness 56 may be selected, along with the material of the load-bearing member 12 as will be discussed below, to meet a specified minimum breaking load requirement. The width 54 of the member 12 is typically in the range of 20-80 mm, and the thickness 56 is typically in the range of the 0.5-3.0 mm, although the width and thickness values may be outside these ranges for a given application. The difference in magnitude between the width 54 and the thickness 56 gives the member 12 significantly more flexibility in one direction than in the other; i.e., the minimum radius for touching the same contact surface 48 , 50 together is significantly less that the minimum radius for touching the same longitudinal edge 52 together.
[0028] The member 12 is formed from a particular material that may be processed (e.g., hot rolled or cold rolled) to create desired mechanical properties; e.g., tensile strength, ductility, etc. Preferably, the load-bearing member 12 is comprised of a single solid material, which material is typically homogeneous throughout its cross-section. As will be discussed in detail below, the member 12 may be used with one or more sheaves 15 , 18 each having a groove 17 with an arcuate profile 19 . A crowned groove 17 causes the member 12 to bend across the width 54 of the member 12 as is diagrammatically shown in FIGS. 4 and 6 ; i.e., the member 12 becomes elastically curved across its width, bending about a lengthwise extending axis. In such elevator systems, the member 12 elastically accommodates such bending and is not, therefore, appreciably deformed by the aforesaid bending over the intended life span of the member 12 . Materials possessing the requisite mechanical properties include ferritic and cold-worked austenitic stainless steels; e.g., the expected bending strains created by crowning are within the elastic region of ferritic and cold-worked austenitic stainless steels. Specific examples of acceptable member materials include type 302 and 430 stainless steel because of their relatively low or no hardening characteristics when subjected to frequent bending as would occur in an elevator system. FIG. 7 provides a table of load-bearing member 12 and drive sheave 18 parameters for exemplary embodiments. In addition to their ability to withstand bending stress, these stainless steel materials are also desirable because of their tensile strength and corrosion resistance. The tensile strength permits the member 12 to be used with a relatively thin cross-section discussed above. In those elevator systems utilizing a counterweight 16 , the counterweight 16 is typically 45-50% heavier than elevator car 14 rated load capacity. The actual breaking strength requirement for the member 12 is a maximum of 55% of the car 14 maximum weight capacity. Thus, multiple thin elements 12 can be utilized. The thin cross-section of the member 12 , in turn, permits the use of drive sheaves 18 having a very small diameter (e.g., in the range of 40-200 mm), relative to conventional drive sheaves (e.g., in the range of 100-1200 mm). A drive sheave 18 with a smaller diameter requires less power than one with a larger diameter. Building space requirements, cost, etc. all benefit from a smaller diameter drive sheave 18 . The present invention load-bearing member 18 is not limited to the aforesaid stainless steel materials, however.
[0029] The longitudinal edges of the load-bearing member 12 may be prepared in a manner that minimizes stress concentrations, edge cracking, etc. to enhance the durability of the load-bearing member 12 . In some embodiments, for example, the longitudinal edges may be formed by laser cut. Laser cutting certain materials into strip form creates a metallurgy with improved fatigue-resistance; e.g., decreased propensity to crack initiation. In some embodiments, the longitudinal edges 52 have an outwardly extending geometry that increases the overall width of the load-bearing member 12 (see FIG. 5 ). For example, the longitudinal edges 52 may be arcuately formed with a radius equal to one-half the thickness 56 of the load-bearing member 12 . The longitudinal edge 52 geometry is not limited to a circular geometry, however, and may have a complex geometry that includes multiple curvatures.
[0030] Now referring to FIG. 6 , a drive sheave 18 used within an elevator system can be integral with a motor 20 (e.g., see FIG. 1 ) or can be coupled to an independent motor 20 . An acceptable drive sheave material is a medium carbon alloy steel sufficient for resistance to bending loads and for localized hardening. A specific example of an acceptable sheave material is AISI 4140. The sheave 18 includes a number of grooves 17 , which number depends on the specific application at hand and the number of load-bearing members 12 utilized to support and/or move the car 14 and counterweight 16 .
[0031] The surface of each groove 17 preferably has a surface roughness that is adequate to provide enhanced traction to the tension member 12 , and localized hardening. Surface preparation techniques such as shot blasting or sand blasting, for example, prior to groove-localized hardening may be used to create an acceptable roughness (e.g., RA 128/256). The surface finish is typically applied to the groove surface regardless of whether the groove 17 is coated, because of the need to control the elevator car 14 in the event of a fire wherein a coating may be compromised. Localized hardening of the grooves 17 (e.g., to HRC 45-50) can be accomplished through techniques such as laser hardening, induction hardening, or flame hardening.
[0032] To keep the load-bearing members 12 in alignment and in their correct groove 17 positions, each groove 17 of the drive sheave 18 preferably has a positive profile 19 (also referred to as a “crown”). Depending on the load-bearing member 12 width and sheave 18 diameter, the crown 19 of each groove 17 may be a radius, for example, in the range of 200 mm to 800 mm. Utilizing crowned grooves 17 will subject the load-bearing members 12 to constant flexing and bending. The present invention load-bearing members 12 , however, are selected to have mechanical properties that can accommodate the aforesaid flexing and bending (e.g., ferritic stainless steels, cold-worked austenitic stainless steels, etc.).
[0033] Groove spacers 30 may be provided between adjacent grooves 17 to inhibit or prevent undesirable load-bearing member 12 movement and noise generated through member-to-member contact. The groove spacers 30 can be an integral part of the machined shaft/sheave or can be a split-ring design. Acceptable materials for split-ring type groove spacers include Teflon or other similar, low-friction materials or coatings.
[0034] Because elevator systems 10 typically operate with different weights attached to each end of the load-bearing members, there are different elongation characteristics between lightly loaded and heavily loaded sides. These differences, side to side, are accommodated as the load-bearing members pass over the driving sheave 18 . There is also continual relative motion between the drive sheave 18 and the load-bearing members, which is referred to as creep, and further relative motion caused by acceleration, deceleration, sudden stops, etc. The relative motion can cause wear on load-bearing members. To accommodate the relative motion, and thereby minimize the aforesaid wear, compliant, high friction coatings (or sleeves) 40 may be applied to the grooves 17 of the drive sheave 18 .
[0035] The high friction materials of the coating/sleeve 40 helps to create adequate traction with load-bearing member 12 , while at the same time providing desirable noise and vibration reduction. Such coatings/sleeves 40 can also act as a sacrificial wear member. Acceptable high friction materials include castable polyurethanes such as PPDI, ether-based MDI, and ether-based TDI. The coating/sleeve 40 can be adhesively bonded to the roughened groove surface 17 . When such a coating sleeve 40 is worn, it can be replaced by removing the spacers 30 and sliding and bonding a new sleeve 40 into position. Where integral spacers 30 are used, worn coatings 40 can be cut and removed. New sheave coatings 40 can be adhesively bonded into position. Thermal polyurethane (TPU) sleeves are typically in the range of two to five millimeters thick.
[0036] While the invention has been described with reference to exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment(s) disclosed herein as the best mode contemplated for carrying out this invention. For example, the above detailed description of the present invention provides examples of elevator system configurations as shown in FIGS. 1 and 2 . The present invention is not, however, limited to these configurations.
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A load-bearing member operable to be driven by a drive sheave in an elevator system is provided. The load-bearing member has a body defined by a thickness, a width that is greater than the thickness, and a length. The body comprises a single solid material that is uniform in the cross-section, and is sufficiently flexible to permit the member to wrap at least partially around the drive sheave of an elevator system. An elevator system is also provided that includes the aforesaid load-bearing members, a car, a counterweight and a drive sheave. The load-bearing members connect the car and counterweight to the drive sheave, and are wrapped at least partially around the drive sheave.
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BACKGROUND OF THE INVENTION
This invention relates to containers, such as shipping containers, for articles having relatively simple shapes. Hundreds of thousands of products such as candles, shock absorbers, flowers, rolls of sheet material, tubes of toothpaste, and so on, are shipped daily, and must be protected from damage. If destined for retail sale, the package should also be attractive and suitable for use at point-of-sale. Yet due to the volume in which many of these products are produced, it is essential that package costs be kept to a minimum.
Some of the costs of a package may not be immediately obvious. Obvious costs, for example, are the sheet material for the package, cutting and creasing the sheet, and folding and erecting the package. However, the cost for the package blank must include the waste material which is discarded when the package is first cut out. A complicated package is also more difficult and time consuming to assemble than a simple one. In addition to these are costs which might be considered hidden, such as strength penalties due to inferior package shape, which then requires heavier material to protect the package contents. To a retailer, another hidden cost would be a package unsuitable for point-of-sale display, thus calling for manual handling and a special display unit.
There is thus a continuing need for containers which provide a maximum amount of strength with the minimum amount of material, which minimize or eliminate wasted material, and which are easy to erect. Such packages should also be versatile, attractive, and convenient for use in a broad range of applications, and should minimize all costs, both apparent and hidden.
SUMMARY OF THE INVENTION
Briefly, the present invention meets the above needs with an extremely strong triangular or wedge-shaped container which can be formed with no waste material from a single rectangular or square blank of sheet material. The blank has three rectangular panels and a fastener, such as a fastening flap, connected to one another by fold lines. Two of the panels also have chevron fold lines at their ends which form triangular end panels for the container. As the blank is folded, the triangular end panels fold inwardly to close the ends of the container, and the fastening flap is secured to the panel opposite it on the blank. This results in a sturdy, secure, and rugged container which is easily assembled and which provides maximum protection for the product it contains.
It is therefore an object of the present invention to provide a triangular container which is formed from a single blank of material; which can be fabricated with no wasted material; which is readily folded and erected; which includes three panels and a fastener connected by fold lines, and two pairs of triangular end panels formed in the ends of two of the adjacent outer panels by chevron fold lines, the triangular panels closing the ends of the container when erected; which may readily be modified for such purposes as display and dispensing; and to accomplish the above objects and purposes in an uncomplicated, inexpensive, strong and versatile configuration readily suited for packaging and shipping a wide variety of products safely and securely.
Other objects and advantages will be apparent from the following description, the accompanying drawings and the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a plan view of a blank from which the container is formed;
FIG. 2 is a perspective view illustrating the initial folding steps in erecting the container;
FIG. 3 is a perspective view of the FIG. 2 blank inverted and further folded;
FIG. 4 shows final folding of the three main container panels;
FIG. 5 illustrates the final assembly step as the fastening flap is folded and secured into position;
FIG. 6 is a plan view of the assembled container;
FIG. 7 is a plan view of the blank for an alternate embodiment for dispensing rolled sheet material;
FIG. 8 is a bottom view of the container formed from the FIG. 7 blank;
FIG. 9 is a cross-sectional view taken on line 9--9 in FIG. 8;
FIG. 10 is a perspective illustration of material being dispensed from the FIG. 8 container;
FIG. 11 is a plan view of the blank for still another embodiment;
FIG. 12 is a plan view of the container formed from the blank in FIG. 11;
FIG. 13 is a side view of the FIG. 12 container; and
FIG. 14 is an end view of the container shown in FIGS. 12 and 13.
DESCRIPTION OF THE PREFERRED EMBODIMENT
With reference to the drawings, FIG. 1 shows a blank 10 having a first end 12 at one end thereof and a second end 13 at the other end thereof. When folded and erected, blank 10 forms the container 15 shown in FIG. 6.
Blank 10 includes first, second, and third outer panels 16, 17, and 18, and a fastening flap 19. Panel 16 has a first edge 20, and is connected to panel 17 along a first fold line 21 on the side of panel 16 opposite edge 20. Panel 18 is connected to panel 17 along a second fold line 22 on the side of panel 17 opposite panel 16. Fastening flap 19 is connected to panel 18 along a third fold line 23 on the side of panel 18 opposite panel 17. Fold line 23, in this embodiment, coincides with a second edge 24 on the side of the third outer panel 18 opposite the second outer panel 17.
A first pair of chevron fold lines 25 starts at the ends of the first and third fold lines 21 and 23 at the first end 12 of blank 10 and converges toward and meets at the second fold line 22. Similarly, a second pair of chevron fold lines 26 starts at the ends of the first and third fold lines 21 and 23 at the other end 13 of blank 10, opposite chevron fold lines 25, and converges toward and meets at the second fold line 22. The chevron fold lines 25 and 26 thus divide the second and third outer panels 17 and 18 into central portions 27 and 28, respectively, a first pair of triangular end panels 30 and 31, respectively, at the first end 12, and a second pair of triangular end panels 32 and 33, respectively, at the second end 13 of blank 10. Likewise, chevron fold lines 25 and 26 divide the second fold line 22 into a central portion 42 and end segments 45 and 46, respectively. Thus triangular end panels 30 and 31 are foldably connected by chevron fold lines 25 to the remainders or central portions 27 and 28 of the second and third outer panels 17 and 18, and foldably connected to one another by segment 45 of the second fold line 22. Similarly, triangular end panels 32 and 33 are foldably connected by chevron fold lines 26 to central portions 27 and 28, and to one another by the second fold line segment 46.
FIGS. 2-5 illustrate the steps in folding blank 10 to erect container 15. The triangular end panels 30-33 are first folded inwardly along the second fold line segments 45 and 46, which are folded to be outwardly concave when the container is completed. Fold lines 21 and 23, chevron fold lines 25 and 26, and the central portion 42 of fold line 22 are folded to be outwardly convex. As illustrated in FIGS. 3 and 4, the first, second, and third outer panels are then folded to give the container a triangular shape. The second and third outer panels (FIG. 3) form two sides of the triangular container, and the triangular end panels 30-33 fold inwardly to close the ends of the container 15. Next (FIG. 4) the first outer panel 16 is folded so that the first edge 20 thereof lies substantially adjacent the third outer panel second edge 23 (which in this embodiment is also the third fold line 23). The ends of the second and third outer panels 17 and 18 at the first and second ends 12 and 13, which are also sides of the triangular end panels 30-33, now lie adjacent the first outer panel 16, closing the ends of the container 15. This completes the folding of the basic container, which is now secured by folding the fastening flap 19 up beneath the first outer panel 16, as illustrated by the arrow in FIG. 5, and suitably securing the fastening flap 19 and first outer panel 16 to one another (such as by gluing or stapling).
Since the triangular container 15 was formed from a rectangular blank, there is no wasted sheet material. The straightforward and uncomplicated configuration also reduces time and labor in preparing and erecting the containers. Further, due to its geometry, the container is very strong and rigid, far more so than a rectangular package of similar sheet material. This inherent strength results in additional cost savings.
The strength of the container is enhanced by the triangular end panels 30-33. These, and the concave fold line segments 45 and 46, are perpendicular to the first outer panel 16, providing extreme resistance to crushing. Furthermore, the concave configuration of the package ends leaves bumper portions 54 and 55 of the first outer panel 16 extending beyond the triangular end panels 30, 31, 32 and 33, respectively.
FIG. 7 illustrates several modifications which may be made to the basic design illustrated in FIGS. 1-6. Thus, the blank 60 in FIG. 7, which is erected in the same manner as blank 10, has a cutting edge 61 secured along the first edge 62 of the first outer panel 63, opposite the second outer panel 64. On the opposite side of the blank 60, in the side of fastening flap 66 opposite the third outer panel 67, is a recess 68. A finger slot 69 may also be provided in one of the panels, such as panel 63. The container 70 which is then formed from blank 60 is suitable for holding and dispensing rolled sheet material 72. Recess 68 allows and guides passage of the material 72 out of the container across cutting edge 61, on which the sheet material may be cut as illustrated in FIG. 10.
Containers 15 (FIGS. 1-6) and 70 (FIGS. 7-10), in cross section, are equilateral triangles (see FIG. 9). FIGS. 11-14 illustrate another embodiment which in cross section (see FIG. 14) is an isosceles triangle. In this embodiment, the blank 80 has a first outer panel 81 which is considerably wider than the second and third outer panels 82 and 83, although of the same length. In order to keep the second fold line segments 85 and 86 perpendicular to the first outer panel 81 when blank 80 is folded to erect the container 88 (FIG. 13), segments 85 and 86 have been appropriately shortened, as will be further described below.
Blank 80 and container 88 illustrate several variations in addition to the isosceles configuration. For example, although blank 80 is erected in essentially the same manner as blank 10, the fastening flap 89 is attached to the first outer panel 81 rather than the third outer panel 83 by a fold line 90 on the first outer panel first edge 91, opposite the second outer panel 82. Fastening flap 89 is also much narrower than panels 81-83, since a full overlap of the first outer panel 81 is often not necessary for securing the erected container. In fact, it is possible to eliminate the fastening flap entirely from the present invention, and to secure the first and second edges of the first and third outer panels to one another instead by some other means such as adhesive tape.
Container 88 includes additional features which make it suitable for point-of-sale display. These include a display window 95 formed by a suitable cutout in the second and third outer panels 82 and 83, and an opening 97 through the first outer panel 81 near one end thereof and within the corresponding bumper portion 98. Display window 95 thus provides for displaying the contents of the package, and opening 97 is suitable for hanging the container on a hook, such as on a display rack.
In the preferred form, the concave segments of the second folding line are perpendicular to the first outer panel in the erected container. This provides maximum strength and rigidity for the container, and eliminates wasted material since a rectangular blank can be used. Otherwise, the ends of the container might not be closed by the triangular end panels 30-33 unless the blank were modified to accommodate concave fold line segments which were not perpendicular to the first outer panel. In the preferred embodiments, therefore, there is a definite relationship among the ends of the first, second and third outer panels at the first and second ends of the blank and the lengths of the concave second fold line segments.
With reference to FIG. 1, the second and third outer panels 17 and 18, including the areas of the triangular end panels 30-33, have substantially equal dimensions. Thus the respective ends 100-103 are of the same length. For convenience in explaining these dimensional relationships, this length is designated a in all embodiments, as shown in FIGS. 1, 9, and 14. The ends 105 and 106 of the first outer panel 16 may be of either the same length a, in which case all three outer panels have substantially equal dimensions, or may be of a different length b, in which case the first outer panel will have dimensions different from those of the second and third outer panels. For purposes of further explanation, the ends of the first outer panel will be designated as having length b, regardless of whether a and b are equal or unequal.
Referring to FIGS. 9 and 15, it will be seen that the triangular cross section of the assembled container has a base b (formed by the first outer panel) and upper sides a (formed by the second and third outer panels). In FIG. 14, the triangle is isosceles, and in FIGS. 5 and 9 equilateral (which is a particular form of isosceles triangle). The height of the triangles is designated by h, and is the length of the concave segments (45 and 46 in FIG. 1) of the second fold line. These dimensions are related by the well-known Pythagorean theorum as follows:
h=1/2√4a.sup.2 -b.sup.2 (1)
a=1/2√4h.sup.2 +b.sup.2 (2)
Therefore, knowing the sizes of the outer panels, equation (1) specifies the exact length of the end or concave segments of the second fold line. The chevron fold lines are then completed by drawing diagonally from the second fold line segments to the ends of the first and third fold lines. Conversely, if one knows how tall the package is to be (h) and how large the base (b), equation (2) specifies the length of the ends of the second and third panels (a).
To illustrate, the following table presents representative dimensions. Length a has been set at unity, and proportionate lengths b and h are provided:
______________________________________a b h______________________________________1.00 .25 .991.00 .50 .971.00 .75 .931.00 1.00 .871.00 1.25 .781.00 1.50 .661.00 1.75 .48______________________________________
The embodiments in FIGS. 1-6 and 7-10 are equilateral, in which a=b=1.00, and h=0.87. (The chevron fold lines 25 and 26, incidentally, have length 1.32.) In the isosceles embodiment in FIGS. 11-14, a=1.00, b=1.75, and h=0.48. (Also, the chevron fold lines equal 1.11).
As may be seen, therefore, the present invention has numerous advantages. It provides a strong and rigid container which can be sized and shaped to protect flowers, axes, toothpaste tubes, artillery shells, toy dolls, and so forth, almost without limit. It is formed from a rectangular blank so that there is no material waste. It is quick and easy to erect, minimizing labor costs. It may be modified, as by the addition of a display window, to serve a variety of end uses, for even greater economy. In addition, the extreme rigidity of the package, and the additional protection provided by the end bumpers, mean that lighter weight board or sheet material may be used, at further cost savings, than for a comparable rectangular container.
While the forms of apparatus herein described constitute preferred embodiments of this invention, it is to be understood that the invention is not limited thereto, and that changes may be made therein without departing from the scope of the invention.
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A single rectangular blank (10) folds easily into a strong and rigid triangular container (15) with no wasted material. The blank may be cut and creased with a single die. The erected container in cross-section may be isosceles or equilateral, according to its contents.
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FIELD OF THE INVENTION
The present invention relates generally to a method for coating a liquid composition onto a substrate surface to form a coating thereon comprising one or more layers. More particularly, the present invention relates to a method for formulating one or more the liquid compositions forming such coating layers, which maximizes the resistance of such compositions to variations in thickness of the layers formed therewith.
BACKGROUND OF THE INVENTION
It is well known to coat a moving web or substrate with a composite layer of liquid coating composition. The composite layer may comprise one or more layers simultaneously coated onto the moving web. Coating can be performed by a variety of methods including, for example, curtain coating, slide bead coating, and extrusion hopper coating with more than one slot. In the manufacture of various types of coated web substrates, a serious problem can arise as a result of variations in thickness of the coated composition in the direction transverse to the coating direction (the direction of travel of the web through the coating apparatus). Such variations are referred to in the art as “running streaks.” In some coating applications, for example, in the manufacture of photographic films and papers, relatively slight variations in thickness, on the order of 1% or less, can render the coating unacceptable.
Such streaks may be formed, from a variety of well-known causes, at any point where the coated composition is still liquid. For example, composition may be caused to move laterally, creating a local increase in composition thickness and leaving a corresponding local decrease in thickness. Thus the practical effect of lateral flow is the sum of the thickness increase and decrease.
Many photographic products are manufactured by a coating technique known in the art as “curtain” coating, wherein liquid composition (also referred to herein as “emulsion”) is extruded from a coating die having a linear coating lip and falls free as a liquid sheet or curtain under gravity onto a substrate passing beneath the die, where it forms a coated layer or layers on the substrate. As is well known in the coating art, the curtain is vulnerable to deformation by air currents impinging on the curtain. Many schemes are known in the art for mechanically shielding the curtain, such as providing close-fitting screens on either side of the curtain or enclosing the die and curtain in a stagnant air chamber. See, for example, U.S. Pat. No. 5,114,759 to Finnicum, et al, U.S. Pat. No. 4,287,240 to O'Connor, and U.S. Pat. No. 5,976,630 to Korokeyi, et al. None of these schemes can be totally successful because of practical considerations such as turbulence caused by entry and exit of the substrate to the chamber and condensation, which can drip from chamber surfaces onto the composition. Further, it has been shown that even very low velocity air currents, on the order of 15 feet per minute or less, can cause unacceptable curtain deformation.
A complementary approach to mechanical shielding is to add surfactant to compositions to be coated to increase resistance to thickness deformation caused by flow of the coating on the web. Many compositions consist of multiple individual layer-forming compositions (referred to herein as “layers” even before the actual point of coating onto the substrate) delivered simultaneously as a coating pack or composite layer from a multiple slot coating die; thus layer compositions exposed to air in a falling curtain may differ between the front side and the back side of the curtain, and each such layer may include surfactant to optimize resistance of the overall coating pack to streak formation. See, for example, U.S. Pat. No. 5,773,204 toBaumlin.
For the purpose of immobilizing (preventing flow of the coating on the web ) and solidifying the coated layers after the coating point, independently of the means used to apply these layers to the support, the coated layers are subjected to air currents that either set (which increases viscosity) and dry them, or simply dry them. The immobilization process typically is done over a period of seconds, during which the coating is subjected to the impact of the air currents. When these currents indirectly impinge on the coated layers, they can lead to thickness variations in the coated layers in the way of a random blotchy pattern referred to in the art as “mottle”. More severe thickness variations can be caused by air currents impinging directly on the coated layers, such as in the form of impinging air jets typically used to produce substantially higher heat transfer rates and accelerate the immobilization rate. The corresponding thickness variations appear as straight lines of some width, which are known in the art as “streaks”.
A difficulty in the art of formulating compositions for coating is determining the optimum concentration of surfactant. Presently, the amount selected is determined empirically by trial and error on representative product layers on a pilot coating machine, or with real product layers on a production coating machine. This approach is known to be very time consuming and costly, especially with regard to the generation of waste or sub-optimal coatings.
Thus, there is a need for a method for simple, off-line determination of the optimum level of surfactant for a coating composition.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide an improved method for predicting the optimal concentration of surfactant for a coating composition.
It is a further object of the invention to provide an improved method wherein simple, inexpensive off-line determinations may be correlated with pilot-scale trial coatings to predict streak or mottle-resistance optima.
Briefly stated, the foregoing and numerous other features, objects and advantages of the present invention will become readily apparent upon a review of the detailed description, claims and drawings set forth herein. These features, objects and advantages are accomplished by measuring the dynamic surface tension (DST) of a proposed liquid coating composition over a range of surfactant levels to determine the surfactant concentration that produces the maximum surface tension gradient. Measurements are made by a method related to the Wilhelmy Blade Method, in which a surface of a static pool of composition to be measured is placed in contact with the lower edge of a suspended blade, and the force required to lift the blade from the surface is determined. The static method is modified such that the surface of the composition touching the blade is continually refreshed, to simulate the formation of fresh curtain surface, by pumping the composition upwards through an open cylinder and allowing the composition to spill over the edges (“overflowing weir”). The bulk surfactant concentration providing maximum resistance to coating streakiness and mottle is highly correlated with the concentration providing maximum surface tension gradients in the overflowing weir. Thus, for new or non-optimized air-contact layers, the optimum surfactant concentration can be predicted quickly and inexpensively through off-line measurement of surface tension using an overflowing weir technique. The technique is suitable for optimizing compositions comprising each of the outer layers of a multiple-layer coating pack in a curtain coating operation, as well as for those compositions comprising the top layer of a multi-layer composite coated in a bead or curtain coating operation. Although much of the method was developed in the context of the curtain itself in a curtain coating operation, surprisingly, it has been found that the method yields a good result for coating processes in general, including, for example, curtain coating, slide bead coating, and extrusion or slot coating, regardless of where the air disturbance occurs. The disturbance may be on the slide surface, in the curtain, or on the web in chill setting or early drying of the coating. In addition, it has been found that the method can also be applied to non-aqueous coatings. Further optimization for specific coating operations and coating formulae can be optimized empirically by those skilled in the art.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an elevational, partially sectioned schematic of prior art apparatus for determining surface tension of a static liquid surface at equilibrium by the Wilhelmy Blade Method;
FIG. 2 is an elevational, partially sectioned schematic showing a prior art overflowing weir apparatus for determining dynamic surface tension of a constantly refreshed liquid surface by the Wilhelmy Blade Method;
FIG. 3 is a graph showing two curves of static and dynamic surface tension of a gelatin composition as a function of the logarithm of the concentration of a surfactant A, the curves representing the system response when measured by the apparatus shown in FIGS. 1 and 2, respectively (where the commercial names of surfactants A through E are given in the Table);
FIG. 4 is a graph of the instantaneous slope of the dynamic surface tension curve shown in FIG. 3, as a function of the logarithm of the concentration of surfactant A;
FIG. 5 is a side elevational, cross-sectional schematic view of a streak-propensity testing device, showing a curtain coating apparatus and an air current generator disposed for controllably blowing air onto the falling curtain;
FIG. 6 is a plot of widthwise percent change in optical density of a representative coating made on the apparatus shown in FIG. 5;
FIG. 7 is a power spectral density graph of the density data shown in FIG. 6;
FIG. 8 is a plot of percent variance in optical density of a gelatin composition as a function of the logarithm of the concentration of surfactant A, when coated via the apparatus shown in FIG. 5;
FIG. 9 is an overlay of the slope of the curve for surfactant A, shown in FIG. 4, and the optical density variance measurements, shown in FIG. 8, showing high correlation of the minima of both measurements;
FIG. 10 is an overlay like that shown in FIG. 9, determined for surfactant B;
FIG. 11 is an overlay like that shown in FIG. 9, determined for surfactant C;
FIG. 12 is an overlay like that shown in FIG. 9, determined for surfactant D;
FIG. 13 is a widthwise measurement of percent variation in optical density of a non-optimized photographic product coated via the apparatus shown in FIG. 5; and
FIG. 14 is a widthwise measurement like that shown in FIG. 13 for the same product after the surfactant level was optimized in accordance with the invention.
FIG. 15 is a plot of experimental measurements of coating thickness non-uniformity caused by air blowing through a perforated plate and impinging on a wet coating, previously applied to a support, for different concentrations and types of surfactant.
FIG. 16 is a schematic side elevational view of a test set-up for an experiment that demonstrates the ability of the method of the present invention to predict the surfactant concentration that minimizes the effect of blowing air on a coated substrate.
FIG. 17 is a plot of experimental measurements of the amplitude of streaks formed by an air jet impinging on a wet coating, previously applied to a substrate, for different concentrations and types of surfactant.
DETAILED DESCRIPTION OF THE INVENTION
Turning first to FIG. 1 there is schematically depicted a prior art apparatus 10 for measuring static surface tension by the Wilhelmy Blade Method. Apparatus 10 includes a shallow vessel 12 opening upwards and containing a static pool 14 of liquid composition to be measured. A blade 16 having height and width but negligible thickness is suspended by hook 18 from a force measurement apparatus (not shown), for example, a beam balance. Blade 16 is brought into contact with the free surface 20 of pool 14 such that the composition wets the lower edge of the blade, forming a meniscus 22 . The force required to lift the blade from contact with the composition is then measured, which force is proportional to the static surface tension (SST) of the composition.
Referring next to FIG. 2, a dynamic surface tension measuring apparatus 24 is schematically depicted. A vessel 26 is continuously fed from below by pump 28 to thereby fill the vessel 26 with liquid 30 . Typically, the diameter of vessel 26 is about 3.8 cm, and the composition is fed to vessel 26 at a flow rate of 8-10 cc/sec, which produces a rate of surface extension similar to that of a free-falling curtain of the same composition during curtain coating from a hopper. The composition continuously overflows the upper edge 32 (the “weir”) of vessel 26 , flows down the outside of vessel 26 and into a circumferential gutter 34 . Liquid collected in circumferential gutter 34 is returned to reservoir 36 , which is the source or reservoir supplying pump 28 such that the liquid can be recirculated back to vessel 26 . Thus, surface 38 of the liquid within vessel 26 expands continuously. The increased surface tension resulting from the continuous depletion of surfactant in the expanding area, as measured by the Wilhelmy Blade Method, is referred to herein as the dynamic surface tension (DST).
Although the following understanding is not presented as fact for purposes of the invention, it is a working hypothesis, which is supported by the facts as presently understood. As composition tends to be displaced laterally, due for example to impinging turbulent air, creating adjacent thicker and thinner areas, the surface in the thinner area is stretched and the surface in the thicker area is compressed. Compositions having a moderate level of bulk surfactant, as discussed more fully below, experience a substantially instantaneous higher surface concentration of surfactant molecules in the thicker, compressed-surface area and a corresponding lower surface concentration in the thinner, stretched-surface area. Such a concentration difference, however, creates a surface tension gradient, which is a restorative force acting to counter the flow, thus countering the tendency to form thickness streaks. Dynamic surface tension σ (also referred to herein as DST) is a direct function of the logarithm of the concentration of surfactant at the free surface, which concentration is changed (dC) when a surface is stretched or compressed to change the surface area (dA). Surface tension gradients are maximized when dσ/dA is maximized.
Two important parameters affecting the surface's ability to form surface tension gradients, and thus its ability to resist formation of streaks and mottle by air currents, are the bulk concentration of surfactant in the composition and the physical mechanisms of surfactant transfer from the bulk to the surface of the composition. First, if the bulk concentration is too high, the transfer mechanisms of surfactant to the surface are very rapid and therefore the surfactant fails to produce significant surface tension differences, thereby preventing the intended leveling action by surface tension gradients. Second, if the bulk concentration is too low, only small differences in the surfactant surface concentration adsorbed to the free surface can be established. The resulting surface tension differences (and their gradients) are also small and therefore sub-optimal for resisting the effects of air currents on the coated layers. Thus, an optimal bulk concentration of surfactant is one in which the associated surface surfactant level is high enough to establish significant differences in surface tension, but is low enough to prevent interference from bulk diffusion and adsorption to the surface during the time period of interest. The time period of interest begins with the formation of the multi-layer structure of the coating and extends to the point in time when the coating is immobilized.
Since increasing surface area decreases the surface concentration, and since the surface concentration is also a function of the bulk concentration, it is useful to examine DST as a function of bulk surfactant concentration. In FIG. 3 two sets of measurements are shown of surface tension of an aqueous gelatin solution over a range of concentrations of a first surfactant. The upper curve 40 represents DST and the lower curve 42 represents SST. The DST curve is of greater interest for the present invention. The dynamic surface tension data plotted against the logarithm of bulk surfactant concentration has a reverse “S” shape. The curves may be conveniently generated by fitting the determined data points to any of several best-fit algorithms, for example, least squares of an equation of similar form to the Carreau equation used to describe rheological behavior in liquids: σ - σ ∞ σ o - σ ∞ = 1 [ 1 + ( λ c ) a ] ( 1 - n ) a ( 1 )
where
σ
dynamic surface tension
σ o
maximum dynamic surface tension (attained in the absence of
surfactant)
σ ∞
minimum dynamic surface tension (attained in the presence of an
over saturation of surfactant)
c
bulk surfactant concentration
λ
fitted parameter
a
fitted parameter
n
slope parameter determined by fitting data
Surface concentration cannot be readily measured directly, but its effect can be observed because of its relationship to bulk concentration. Thus curve 40 really represents the effect of surface concentration on surface tension, although it is plotted as a function of bulk concentration. The surface tension gradient can be represented as the slope of curve 40 , the minimum value of the slope occurring at the inflection point 44 .
The values of the slope for the DST curve 40 shown in FIG. 3 may be plotted against concentration, as shown in FIG. 4 . The steepest or maximum slope of the curve in FIG. 3 occurs at the curve minimum 46 , in FIG. 4, and represents the surfactant concentration providing the largest surface tension gradients to the system. The terms “steepest slope” and “maximum slope” as used herein are intended to refer to the largest absolute value of the rate of change. In accordance with the above-described hypothetical mechanism, this concentration should provide maximum resistance to surface-deforming forces. Following common use, the surfactant concentration at which the curve minimum occurs in any plot like that of FIG. 4, is referred to herein as the surfactant concentration at which surface tension gradients are maximized. Furthermore, all references to maximum, optimum or largest surface tension gradients refer to this surfactant concentration.
The method of the present invention is tested by curtain coating the same compositions over a range of bulk surfactant concentrations under conditions of controlled imposed air disturbance, and evaluating the coatings for resistance to such disturbance. FIG. 5 shows an exemplary apparatus 50 for making such coatings. A coating die 52 , also known as a coating hopper, having a predetermined composition delivery width, is positioned within an enclosure 54 a above a coating backing roller 56 around which a web 58 , having a width greater than die delivery width, is conveyed to be coated. Enclosure 54 preferably is provided with a low-velocity baffled air supply and exhaust ports 60 , 62 to prevent condensation within the enclosure 54 . A coating composition 64 to be tested is provided to die 52 at a controlled flow rate from a solution delivery system (not shown) in known fashion. Composition 64 falls from die lip 66 as a free-falling curtain 68 that impinges on web 58 to form a coated layer or composite layer 70 . Below die 52 is mounted an air disturbance generator 72 through which controlled air currents 74 can be impinged onto free-falling curtain 68 . Coatings made with apparatus 50 are dried conventionally in dryers (not shown).
Coatings may be analyzed for widthwise variation in optical density, as shown in FIG. 6, and a power spectral density determined by conventional analysis, as shown in FIG. 7 . Optical density is directly proportional to physical thickness in accordance with Beer's Law. The power value is a measure of the variance of optical density with distance and is calculated from the power spectrum over the frequency range of interest (50-110 Hz). This frequency range represents broad streakiness on the order of 1.80 to 4.25 cm in wavelength. The square root of the average variance in the 50 to 110 Hz band, expressed as a percentage (“% optical density” in the examples shown) is the uniformity measure of interest for comparison of surfactant behavior. A higher % optical density value indicates a less uniform coating.
Power values for the range of coatings noted above are plotted as a function of their individual bulk concentrations of surfactant, as shown in FIG. 8 . When the data in FIGS. 4 and 8 are superimposed, as shown in FIG. 9, it can be seen that the compositions having the largest surface tension gradient have a very high correlation to the compositions having the lowest variation in coating non-uniformity. Thus, optimizing surface tension gradients is an excellent predictor for maximizing the streak-formation resistance of a composition.
FIGS. 10-12 show similar high levels of correlation, and therefore predictability, for four other gelatin compositions containing four different surfactants.
For confirmation, the method of the present invention was tested. A test photographic product made with the method of the present invention was compared with a prior art version of the product. FIG. 13 shows the widthwise uniformity of the existing product when coated via apparatus 50 (see FIG. 5 ). FIG. 14 shows the improvement in widthwise optical density uniformity when the surfactant concentration in the test product was optimized in accordance with the present invention.
The method of the present invention has also been tested on wet coatings, applied to a moving substrate, which have been disturbed by blowing air over them, and the correlation with the method of this invention is also very good. In both experiments described below, the coating was applied to the substrate using the slide coating method. Thus, the method of the present invention does not depend on the multi-layer coating method employed.
In the first of these applications, three layers were applied simultaneously on a clear substrate. The middle layer contained a carbon dispersion to provide optical density. Air was blown onto the coated side of the substrate through a perforated plate, which causes the coating to flow. This is demonstrated by the variability of the optical density of the coating and, according to Beer's Law, this variability in optical density can be directly related to the variability in the thickness of the middle layer. In these experiments, the concentration of the surfactant placed in the top layer is the only parameter that was changed. All other parameters were held constant. This includes the viscosity of the coating liquid as delivered to the coating hopper, the thickness of the coated layers, the speed of the substrate on which the coating was applied, the flow rate of the air through the perforated plate, and the dimensions and the distance of the perforated plate from the wet substrate. The method of measuring the optical density variations was very similar to the method that was applied previously to measure disturbances in the curtain. However, the frequency range of the power spectrums considered here corresponded to wavelengths of mottle disturbances having a size scale in the range of from about 1.25 cm to about 5 cm, and these measurements were recorded simultaneously at both ends (in the coating direction) of the perforated plates. The measurement at the start of the perforated plate is taken to eliminate from the measurement at the end of the perforated plate optical density variations that may exist in the coating before it is subjected to the blowing air. Therefore, the variability of the coating thickness, caused by the air blowing on the wet coating, is estimated as the difference between the variances in the power spectrums (in the mentioned limited frequency range) of the two signals. This measurement is named “Band power (out-in)” and is shown in FIG. 15 for a series of surfactant concentration levels and for surfactants A, C, and D of the Table below. The experiment performed to generate the data presented in FIG. 15 was not carried to the point of yielding optimum surface concentration of surfactant. However, the plots demonstrate very well the trend that increasing surfactant concentration beyond optimum concentration increases the non-uniformity caused by air disturbances.
TABLE
List of Surfactants Tested
Label
Commercial Name
A
Triton X-200
B
Zonyl FSN
C
Olin 10G
D
Alkanol XC
E
Aerosol OT
Next is described another experiment that demonstrates the ability of the method of this invention to predict the surfactant concentration that minimizes the effect of blowing air on a coated substrate. Referring to FIG. 16, a gelatin coating 100 containing a carbon dispersion was applied to a moving substrate 102 and a stationary jet 104 directed air at the wet gelatin coating 100 on the substrate 102 . The impinging air from jet 104 formed a streak in the coating 100 that was measured from an image taken with a digital camera 106 shortly after the impingement area. A light 108 was provided on the underside of the web 102 to back light the area being imaged with the digital camera 106 . The streak had been caused by a thickness variation in the coating that was measured from the image by appropriately applying Beer's Law. The following parameters were kept constant: the coating's wet thickness, the speed of the coated substrate, the stationary jet 104 and its position, and the flow rate of air exiting stationary jet 104 . Surfactant was mixed, in differing amount or type, into a container that held a small amount of the aqueous gelatin solution with carbon dispersion. This solution came from a batch that had been prepared previously for use throughout the test. FIG. 16 shows the resulting thickness variation for the different surfactants in terms of their concentration. The thickness variation is given as the “Streak amplitude”, which is the variation in the coated layer thickness through the breadth of the streak, divided by the average thickness of the coating. The curves of streak amplitude for the different surfactants and the concentration levels for the minimum streak amplitude shown in FIG. 16 compare remarkably well with those of the surfactant gradients shown in FIGS. 9, 11 , and 12 .
Surprisingly, the method also appears to apply to streaks formed on the slide in the layers of a film with multiple layers, even when the streaks are produced by other means than air disturbances. Such streaks may, for example, be caused by obstructions in the slots or on the slide surface of the coater.
From the foregoing, it will be seen that this invention is one well adapted to obtain all of the ends and objects hereinabove set forth together with other advantages which are apparent and which are inherent to the apparatus.
It will be understood that certain features and sub-combinations are of utility and may be employed with reference to other features and sub-combinations. This is contemplated by and is within the scope of the claims.
As many possible embodiments may be made of the invention without departing from the scope thereof, it is to be understood that all matter herein set forth and shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense.
Parts List:
10
prior art application
50
exemplary apparatus
12
shallow vessel
52
coating die
14
static pool
54
enclosure
16
blade
56
backing roller
18
hook
58
web
20
free surface
60
exhaust ports
22
forming meniscus
62
exhaust ports
24
measuring apparatus
64
coating composition
26
vessel
66
die lip
28
pump
68
freefalling curtain
30
liquid
70
composite layer
32
upper edge
72
disturbance generator
34
circumferential gutter
74
air currants
26
reservoir
100
gelatin coating
38
surface
102
substrate
40
upper curve
104
stationery jet
42
lower curve
106
digital camera
44
inflection point
108
light
46
curve minimum
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A method for measuring the dynamic surface tension (DST) of a proposed outer layer of a liquid composition, to be curtain or slide hopper coated, over a range of surfactant levels to determine the surfactant concentration which produces the maximum resistance to air currents. Measurements are made by the Wilhelmy Blade Method, in which a surface of a pool of composition to be measured is placed in contact with the lower edge of a suspended blade. The static method is modified such that the surface of the composition touching the blade is continually refreshed to simulate the formation of fresh curtain surface by pumping the composition upwards through an open cylinder and allowing the composition to spill over the edges (“overflowing weir”). The bulk surfactant concentration providing maximum resistance to coated streakiness or mottle is highly correlated with the concentration providing maximum surface tension gradients in the overflowing weir apparatus. Thus, for new or non-optimized air-contact layers, the optimum surfactant concentration can be predicted quickly and inexpensively through off-line measurement of surface tension using the overflowing weir technique.
| 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a two-component mortar composition which is based on unsaturated polyesters suitable for securing elements used in construction.
2. Description of the Prior Art
It has long been known to use ampules or similar containers having destructible wall material for securement purposes, e.g., for securing stays, such as, tie bars, and for rock stabilization in mining. This is accomplished by inserting the container into a borehole. Besides fillers and, if necessary, other auxiliaries, these ampules which are frequently referred to as mortar cartridges, contain a hardenable synthetic material and, separately, a hardener intended for this material. By driving the stay or reinforcing device into the borehole, optionally with simultaneous rotary motions, the wall of the ampule is destroyed, the partition between the hardenable synthetic material and the hardener is removed or destroyed, and some degree of mixing is effected which finally leads to curing of the synthetic material. In this process, good mixing is of essential importance in order to avoid the formation of pockets of unreacted material. Manually, this can be accomplished only with difficulty, so that the rotary motion is usually effected by machine. With good mixing, the fillers contained in the hardenable synthetic resin composition permit compression and extension-resistant and essentially shrinkage-free curing to take place.
It is also possible to mix the two components which react with curing, after they are delivered separately, e.g., in drums, and to feed them into the boreholes with auxiliary equipment, such as, injection tubes, trowels or hoses.
Viscosity is a major problem when such hardenable synthetic resin compositions are used for securing purposes. At building sites, for example, it must be taken into account that work will have to be carried out within a relatively wide temperature range, for example, from +5° to +40° C. On the one hand, the viscosity should be sufficiently low at lower temperatures so that the composition does not have too high a flow resistance and can be applied by means of a handgun. A low viscosity is also important so that the mixing tools can achieve satisfactory mixing. On the other hand, the properties of the composition in the upper temperature range should be such that the composition does not drip after the pressure of the handgun is released and does not run out when applied horizontally or vertically overhead.
Prior to the present invention, a manually injectable two-component composition which can be metered out and which, after being mixed by means of a static mixer, secures the stay, e.g., a plug-in tie bar installed by hand power, with a strength comparable to the strength of the tie rod, was not known. Such a two-component composition which can be fed into a borehole by hand with, for example, a conventional handgun using two cartridges and a static mixer, would be highly desirable because of the ease of handling and the independence from having to use machinery.
SUMMARY OF THE INVENTION
We have discovered a mortar composition which is free of the former disadvantages and which has the above-noted desirable properties. More particularly, the present invention comprises a two-component mortar composition based on unsaturated polyesters, reactive diluents, fillers, thixotropic agents, and other optional conventional additives, as well as a free radical curing catalyst, wherein the unsaturated polyester is contained in the one component and the hardener is contained in the other component. In accordance with the invention, a total of 15-35 weight percent of unsaturated polyester, 9-25 weight percent of reactive diluent, 44-46 weight percent of filler, 0.5-4 weight percent of thixotropic agent, and 1-6 weight percent of free radical curing catalyst are present, the percentages being based in each case on the total composition. Such compositions, on the one hand, have the desired strength level and, on the other, show the required viscosity behavior.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The attendant materials, such as, reactive diluents, fillers, thixotropic agents and other conventional auxiliaries, such as, stabilizers, extenders, etc., can be contained in the polyester component as well as in the hardener component or in both components. Preferably, however, the reactive diluent is contained in the polyester. The only critical factor is that the sum of the components falls within the inventive limits defined above.
A modification in which the two-components, that is, the component containing the unsaturated polyester, and the component containing the hardener, have approximately the same viscosity, is particularly advantageous. This can be achieved, for example, by the hardener component containing a carrier which is inert in relation to the hardener activity and/or, relative to the total composition, a portion of the filler and/or the thixotropic agent. Accordingly, the hardener may, for example, be present in the form of a 30-70% paste of dibenzoyl peroxide in a phthalate plasticizer. Typically, this could be a 50% paste. It may optionally include a portion of the total amount of fillers required, for example, quartz with a particle size of 0.04-0.15 mm in a mixing ratio of paste to quartz of approximately 2:1 parts by weight. In each case, the amounts of fillers and/or thixotropic agents introduced with the hardener together with the fillers and/or thixotropic agents contained in the unsaturated polyester component, form the specified total content of these components in accordance with the invention.
The polyester resins which can be used within the scope of the present invention as unsaturated polyesters, are those which are conventionally used for such a purpose. Preferably, these are polyesters from lower, unsaturated discarboxylic acids, aromatic dicarboxylic or polycarboxylic acids, optionally also with condensed rings and lower aliphatic polyols, particularly diols. Especially preferred examples are unsaturated polyesters from maleic acid, o-phthalic acid and propylene glycol as a 65% solution in styrene, preaccelerated with tertiary aromatic amines and stabilized with phenolic inhibitors. Fumaric acid can also be used instead of maleic acid. The ratio of maleic acid to o-phthalic acid can vary from 2:1 to 1:2.
Because of their reactivity, amine-accelerated polyesters are preferred.
The unsaturated polyesters can be introduced as such, in admixture with fillers and the like, or with other solid or liquid carriers, e.g., in the form of their solutions. Inert carriers can be used as the solvent, even though reactive diluents are preferred. The usual α-olefin compounds, which are known as reactive diluents, such as, for example, styrene and divinyl benzene, may be used as reactive diluents. The mixing ratio of unsaturated polyester to reactive diluent generally falls within the range of 2:0.8 to 2.5 parts by weight, a mixing ratio of about 2:1.5 parts by weight being particularly suitable.
In a preferred embodiment, the unsaturated polyester and the reactive diluent together comprise 36-40 weight percent of the inventive hardenable mortar composition.
The preferred filler is quartz although mineral fillers conventionally employed for such purposes, such as, kaolin, barium sulfate, glass fiber, glass spheres and the like, can also be used. Preferably therefore, the inventive compositions contain essentially quartz as filler, for example, 65 weight percent and more, and preferably more than about 80 weight percent, based on the total amount of filler, the use of quartz as the only filler has proven to be particularly successful. In accordance with the invention, the quartz particles generally have a diameter of 0.1 to 0.6 or even of 0.1 to 0.25 mm. Generally, at least 50%, preferably more than 60%, and frequently even more than 80% of the total number of particles fall within this particle size range. A typical particle size distribution in accordance with the invention is approximately as follows:
______________________________________Particle Size Silica Sand Silica SandDistribution 0.1-0.25 mm 0.1-0.65 mm______________________________________>250 μm 4.9% 66.5%250-125 μm 81.9% 25.3%125-90 μm 10.9% 6.8%90-63 μm 2.0% 1.1%63-32 μm 0.3% 0.1% <32 μm 0.1% 0%______________________________________
The usual quartz grains can be used even though fire-dried quartz grains with rounded edges are especially preferred. The fillers, particularly the quartz, are preferably surface-treated with coupling agents, such as, for example, silanes.
Conventional materials can be used as thixotropic agents, even though materials, such as pyrogenic silica, especially pyrogenic silica which has been surface treated with an organic compound to enhance the thixotropic effect and moreover, kaolin, bentonite, montmorillonite, asbestos and/or organic fiber materials are preferred. Mixtures of bentonite and montmorillonite have proven to be very suitable. The thixotropic agents have an appreciable effect on the flow behavior of the inventive composition. Even in the low viscosity range, the thixotropic agent should prevent the inventive composition from running out of the boreholes in horizontal or overhead installations. Furthermore, the thixotropic agents counteract sedimentation of the fillers and therefore noticeably increase storage stability. Thus, the thixotropic agents are preferably contained in the component which also contains the filler. Alternatively, they can be divided between the components in proportion to their filler contents.
The hardener, contained in the hardener component for curing the unsaturated polyester, is a conventional free radical catalyst. Organic peroxide compounds, such as, for example, dibenzoyl peroxide, are preferred.
The hardener may be contained in an inert carrier, for example, a plasticizer for the polyester resin, such as, for example, a phthalate plasticizer. Inventive compositions, in which the hardener component contains the inert carrier as well as certain amounts of filler and/or thixotropic agents and has about the same viscosity as the component containing the unsaturated polyester, have been especially successful.
The inventive compositions may furthermore contain other conventional additives, such as, pigments, dyes, extenders, viscosity modifiers, solvents and the like.
The curing of the inventive mortar composition is initiated by intimately mixing the polyester component with the hardener component in a known manner. At room temperature, curing times generally fall within the range of 30 to 60 minutes and load absorption is possible within the range of permissible load values after only about 5 minutes.
In accordance with a particularly preferred modification, the inventive two-component mortar compositions contain, in total or mixed for curing, 20 to 24, and especially, 21 to 21.5 weight percent of unsaturated polyester, 12 to 20, and especially, 14 to 17 weight percent of reactive diluent, 46 to 59 and, especially, 52-57 weight percent of filler, 1 to 3, and especially, 1.0 to 2.5 weight percent of a thixotropic agent and especially from 2.5 to 4.5 weight percent of a free radical curing catalyst, the percentage in each case being based on the total composition.
The inventive hardenable mortar compositions are used especially as mortar compositions for securing tie bars in boreholes in solid material, such as, concrete, masonry, rock and the like, that is, as essentially homogeneous, hard materials. In this connection, it has proven to be particularly successful to use mortar compositions, the particle size of whose quartz filler falls within the lower range, for smaller tie bars, while mortar compositions, the particle size of whose quartz filler falls within the upper range are used for larger tie bars. Particle size ranges from about 0.1 to 0.25 mm have proven to be particularly successful for securing M 6-M 16 tie bars with a maximum annular gap of 1 mm, while particle size ranges from about 0.4 to 0.6 mm have proven to be particularly successful for securing larger tie bars with annular gaps from about 1 to 2 mm.
The following examples illustrate a two-component mortar composition in accordance with the present invention:
EXAMPLE 1
Highly filled, unsaturated polyester mortar
______________________________________Unsaturated polyester resin 32.0%(70% solution in styrene)Benzoyl peroxide 2.0%(50% solution in phthalate)Pyrogenic silica 1.0%Silica sand 0.1 . . . 0.45 mm 65.0% 100.0%______________________________________
EXAMPLE 2
______________________________________Unsaturated polyester 32.5%(60% solution in styrene)Benzoyl peroxide 6.0%(50% solution in phthalate)Pyrogenic silica 2.5%Silica sand 0.1 . . . 0.25 mm 55.0%(posttreated with silane) 100.0%______________________________________
EXAMPLE 3
Filled, unsaturated polyester mortar
______________________________________Unsaturated polyester 38.0%(65% solution in styrene)Divinyl benzene 3.5%Pyrogenic silica 3.5%Benzoyl peroxide 10.0%(50% solution in phthalate)Silica sand 0.1 . . . 0.6 mm 45.0% 100.0%______________________________________
For curing, the polyester-containing component and the hardener-containing component are mixed in the proportions appropriate for obtaining the inventive compositions. For the sake of simplicity, specified mixing ratios are generally used. However, the mixing ratios can be modified readily within the inventive range.
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A two-component mortar composition for securing stays and for rock stabilization in mining having an unsaturated polyester in one component and a hardener material in the other. The composition comprises a total of 15 to 35 weight percent of unsaturated polyester, 9 to 25 weight percent of reactive diluent, 44 to 66 weight percent of filler, 0.5 to 4 weight percent of thixotropic agent, and 1 to 6 weight percent of a hardener which is a free radical curing catalyst. The composition exhibits desired strength levels and also exhibits the desired securing properties for mortar compositions as well as ease of handling.
| 2 |
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention is related to a colorant compound isolated from a reaction of Genipa americana derived genipin and glycine.
[0003] 2. Description of Prior Art
[0004] The blue pigment derived from a reaction of genipin or structural analogs and amino acids have been “found to be an intractable mixture of high molecular polymers on the basis of its chromatographic behavior, un-analyzable 13C-NMR spectrum and by molecular weight measurements” (see Touyama R. et al., Studies on the Blue Pigments Produced from genipin and methylamine. I. Structures of the Brownish-Red Pigments, Intermediates Leading to the Blue Pigments, Chem Pharm. Bull 42 , 66 , 1994 ). Therefore, there has been a limited description of the blue pigment material molecular structure since this material is almost soluble only in water due to its very high polarity which results in hard TLC monitoring. A polymer of 9000 molecular weight has been reported (see H. Jnouye, Y. et al., 26 th Symposium on the Chemistry of Natural Product , Kyoto, Abstr. pp 577-584, 1983).
[0005] The present invention contributes to overcome the lack of knowledge regarding the molecular structures of the blue pigment material derived from a reaction of genipin with an amino-acid.
SUMMARY OF THE INVENTION
[0006] The present invention provides colorant compounds and its molecular structural formulas and methods of isolation of the colorant compounds derived from a reaction of Genipa americana genipin and glycine. The novel compounds were obtained from multiple fractioning by chromatography of the reaction resulting material. The molecular structural formulas resulted from 1 H nuclear magnetic resonance spectroscopy ( 1 HNMR), J-Modulation (JMOD), H—H Correlation Spectroscopy (COSY 1 H- 1 H) experiments, and other molecular structural tools analysis.
[0007] Specifically, the present invention provides a colorant compound of the formula 3A (For all purposes in the present Application, formula 3A is for compound No. 3 in the preferred isomeric form):
[0000]
[0008] In a less preferred embodiment of the colorant compound of the present invention, said colorant compound, has the isomeric form of formula 3B (For all purposes in the present Application, formula 3B is for compound No. 3 in the a less preferred isomeric form):
[0000]
[0009] The present invention also provides a method of isolating the colorant compound of formula 3A:
[0000]
[0010] Wherein the methods comprises:
A. Isolating genipin from Genipa Americana juice; B. Reacting glycine with said genipin to obtain a material soluble in methanol; C. Separating by chromatography the material soluble in methanol into S1, S2, S3, and S4 fractions. D. Separating again by chromatography the S3 fraction into S31, S32, S33 and S34 fractions. Isolating by reverse phase chromatography from the S33 fraction the compound of formula I.
[0015] In a less preferred embodiment of the method of the present invention, the compound has the isomeric form of Formula 3B:
[0000]
[0000] the method comprising:
A. Isolating genipin from Genipa Americana juice; B. Reacting glycine with said genipin to obtain a material soluble in methanol; C. Separating by chromatography the material soluble in methanol into S1, S2, S3, and S4 fractions. D. Separating again by chromatography the S3 fraction into S31, S32, S33 and S34 fractions. E. Isolating by reverse phase chromatography from the S33 fraction the compound of formula I.
[0021] Additional objectives and advantages of the present invention will be more evident in the detailed description of the invention and the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 . shows chemical formulas for both isomeric forms of compound No. 1.
[0023] FIG. 2 . shows another representation of the chemical formulas for both isomeric forms of compound No. 1.
[0024] FIG. 3 . shows chemical formulas for both isomeric forms of compound No. 3.
[0025] FIG. 2 . shows another representation of the chemical formulas for both isomeric forms of compound No. 3.
[0026] FIG. 5 . shows a nuclear magnetic resonance (NMR) spectroscopy spectra of compound No. 1.
[0027] FIG. 6 . shows a nuclear magnetic resonance (NMR) spectroscopy spectra of compound No. 3.
[0028] FIG. 7 . shows the a nuclear magnetic resonance (NMR) for the S31, S32, S33, and S34 fractions derived from the S3 fraction.
DETAILED DESCRIPTION OF THE INVENTION
[0029] FIGS. 3-3A and 4 - 4 A show representations of the chemical formula for the preferred isomeric form of compound No. 3. Compound No. 3 is a very dark blue colorant substance. FIGS. 3-3B and 4 - 4 B shows the less preferred isomeric form of compound No. 3. FIG. 6 shows the nuclear magnetic resonance (NMR) spectroscopy profile of compound No. 3. Analysis of the NMR spectroscopy profile of compound No. 3. Shows:
[0030] 1 H NMR (400 MHz, D 2 O). δ 8.6, 8.0, 7.9, 6.7, 3.90, 1.8 ppm.
[0031] 13 C NMR (100 MHz). δ 172.2, 166.3, 138.8, 135.6, 135.1, 133.3, 131.4, 127.1, 120.46, 118.9, 61.0, 53.3, 11.2 ppm. m/z 505 [M+H]
[0032] Further analysis of compound No. 3 showed that:
[0033] The mass spectra of the compound 3 displayed m/z=505 [M+H] + in mass spectrometry, so indicating an isomer of the compound previously described. However, the 1 H and 13 CNM spectra were very different to that one. In the proton spectra, the following singlets were detected: δ 8.0, δ 7.9, and δ 6.7 (2H each one) and one additional singlet at δ 8.6 integrating for 1H. Other signals were a singlet at δ 4.7 (N-CH2) and two methyl groups at δ 3.9 (OCH 3 ) and δ 1.8 (CH 3 vinyl. According to JMOD experiment, the following carbon atoms were observed too: a carboxyl group at δ 172.2, a methylester at δ 166.3, (COOH), five quaternary carbon atoms at δ 138.8, δ 135.1, δ 127.1, δ 120.4, δ 118.9, four methines at δ 135.6, δ 133.3, δ 131.4, δ 131.4, one methylene (N-—(CH 2 ) at δ 61.0 and two methyl groups at δ 53.3 (OCH 3 ) and 11.2 (CH 3 vinyl). The structure of each monomer unit was assigned according to HMBC experiment: signals at δ 7.9 and δ 8.0 were assigned to protons of the pyridil group, since a long range correlation to the N-methylene group at δ 61.0 was detected; additionally the last proton display 3 J coupling to the methylester carbonyl at δ 172.2. Besides other important coupling was shown between the singlet at δ 131.4 (C-7) with protons of the methyl group. The low amounts of aromatic and vinyl proton indicated the presence of a symmetric dimeric molecule such as is showed in FIG. 3 . Two structures could be assigned to this molecule, according to the relative orientation of the methylester group (( 3 A and 3 B)( FIG. 3 ), but structure B has a low probability due to steric hindrance, again.
[0034] The present invention also provides a method of isolating the colorant compound No. 3.
[0035] Wherein the methods comprises:
A. Isolating genipin from Genipa Americana juice; B. Reacting glycine with said genipin to obtain a material soluble in methanol; C. Separating by chromatography the material soluble in methanol into S1, S2, S3, and S4 fractions. D. Separating again by chromatography the S3 fraction into S31, S32, S33 and S34 fractions ( FIG. 7 ). Isolating by reverse phase chromatography from the S33 fraction the compound of formula I.
[0040] For the purpose of the present Application the terms S1, S2, S3, S4, and S31, S32, S33 and S34 are a way to define the fractions derived from the described steps of the method. However, these terms (S1, S2, S3, S4, and S31, S32, S33 and S34) cover any fractions obtained by similar chromatographic steps and which could be derived from a reaction genipin and glycine, wherein a S3 similar fraction and S3 derived fractions (of similar NMR spectroscopy as shown in FIG. 7 ) are produced. FIG. 7 shows the NMR spectroscopy of the S3 fraction derived S31, S32, S33 and S34 fractions.
[0041] Although the description presents preferred embodiments of the present invention, additional changes may be made in the form and disposition of the parts without deviating from the ideas and basic principles encompassed by the claims.
EXAMPLES
[0042] Genipin Isolation from Genipa Americana Juice
[0043] A solid lyophilized (900 grams) from 10 liters of Genipa americana green juice was Soxhlet extracted with dichloromethane; the generated solvent was evaporated under reduced pressure resulting in a brown residue (240 g); an aliquot of 1 gr was separated by exclusion chromatography by size using, as mobile phase, a mix of hexane/methanol/dichloromethane (2:2:1) from which there were four resulting fractions; genipin was identified in one of the fractions using fine layer chromatography and by comparing with a previously know genipin patter. The fraction containing the genipin was purified multiple times with a chromatographic silica gel column and a hexane/ethyl acetate mobile phase until a pure product (200 mg of genipin) was obtained according to RMN spectra.
Reaction of Genipin and Glycine
[0044] Glycine (200 g) dissolved in water (200 ml) was heated a 70°. Then, genipin (5 g) in methanol (10 ml) was added and the mix was agitated for four hours. The reaction mix was lyophilized and the blue powder was extracted with ethyl-acetate in order to eliminate genipin excess and other low polar components.
Fractioning of New Components
[0045] The blue powder was extracted with methanol (5×100 ml), the generated solvent was evaporated under reduced pressure and a blue resin (2.2gr) was obtained. The blue resin dissolved in methanol 90% was separated in a Sephadex® LH 20 (methanol mobile phase) resulting in four fractions which were denominated (for purposes of this patent Application) S1, S2, S3 and S4.
[0046] The S2 fraction was separated using an adsorption resin (Amberlite® XAD-7) using initially 15% ethanol and ending with 95% ethanol. Four sub-fractions were generated from S2. These S2 sub-fractions were denominated (for purposes of this patent Application) M2S1R, M2S2R, M2S3R and M2S4R. The M2S1R was RP-C18 separated several times with different mobile phases (mixes of ethanol-water and methanol-water) until a two compound were obtained, one of those two compounds was denominated compound No. 1 (7 mg). Spectroscopic characteristics of compound No. 1 are:
[0047] 1 H NMR (400 MHz, D 2 O). δ 8.77, 8.53, 7.54, 5.30-4.95, 3.94, 2.25, 1.66 ppm.
[0048] 13 C NMR (100 MHz). δ 170.0, 164.16, 157.80, 157.44, 148.29, 146.41, 139.76, 137.83, 124.16, 63.35, 62.6, 56.19, 53.89, 17.43, 14.93 ppm.
[0049] Further analysis of compound No. 1 showed that:
[0050] In 1 H NMR displayed a few signals: two aromatic protons as singlets at δ 8.77 and 8.53, a vinylic proton at 7.54, a singlet at 4.95, (2H) and three singlets integrating for 3H each one at 3.94 (OCH 3 ), 2.25 (vynilic methyl group), and 1.66.
[0051] The JMOD experiment displayed the following signals: three methyl groups at 14.93, 17.43 and 53.89, one methylene at 62.68, assignable to a methylene derived from glycine, three methine at 157.44, 146.41, 137.83 and finally, seven quaternary carbon atoms at 170.00 (carboxylic), 164.16 (methyl ester carbonyl), 157.80, 148.29, 139.76, 124.16 and 53.89. So, the genipin moiety and glycine residue has been conserved, but molecule now is aromatic with a pyridil residue, due to position of the protons and carbons atoms in NMR spectra. However, a new methyl group been appeared in the structure and his position was assignable on the basis of JMOD, HMQC and HMBC experiments. So, COSY 1H-1H showed an allylic connectivity between methyl group at 2.25 with vynilic proton at 7.54; in the HMBC experiment this proton displayed 3J coupling to these methyl (157.44 in 13C NMR) and the aliphatic methyl group at 14.93 (1.66 in 1H NMR), which in turn, establish a correlation to the quaternary carbon atom at 53.89 and aromatic at 157.80 and 148.29. Other long range connectivities detected were: N-CH2 (62.68) to both aromatic protons at 8.77 and 8.53, and the former to methylester carbonyl. Finally, MS exhibited a m/z 522 [W+H] indicating a symmetric dimeric molecule, as can be seen in FIGS. 1 and 2 . The connecting bridge between monomers was deduced through C-8 and C-8′ carbon atoms, since apparition of a methyl group as a singlet, which is mutually coupled to the other methyl group in the HMBC experiment. There are two possible isomers as it is shown in 1A, 1B, 2A, 2B of FIGS. 1 and 2 .
[0052] The S3 fraction was separated by chromatography with Sephadex® using a 95% methanol mobile phase generating four S3 fractions that for the purpose of this patent Application were denominated S31, S32, S33, and S34. The S33 fraction was separated several times by RP-C18 reverse chromatography using different mobile phases (mixes of ethanol-water and methanol-water) until a compound, which was denominated compound No. 3 (4 mg) was obtained. The Spectroscopic characteristics of compound No. 3 are:
[0053] 1 H NMR (400 MHz, D 2 O). δ 8.6, 8.0, 7.9, 6.7, 3.90, 1.8 ppm.
[0054] 13 C NMR (100 MHz). δ 172.2, 166.3, 138.8, 135.6, 135.1, 133.3, 131.4, 127.1, 120.46, 118.9, 61.0, 53.3, 11.2 ppm. m/z 505 [M+H]
[0055] Further analysis of compound No. 3 showed that:
[0056] The mass spectra of the compound 3 displayed m/z=505 [M+H] + in mass spectrometry, so indicating an isomer of the compound previously described. However, the 1 H and 13 CNM spectra were very different to that one. In the proton spectra, the following singlets were detected: δ 8.0, δ 7.9, and δ 6.7 (2H each one) and one additional singlet at δ 8.6 integrating for 1H. Other signals were a singlet at δ 4.7 (N-CH2) and two methyl groups at δ 3.9 (OCH 3 ) and δ 1.8 (CH 3 vinyl. According to JMOD experiment, the following carbon atoms were observed too: a carboxyl group at δ 172.2, a methylester at δ 166.3, (COOH), five quaternary carbon atoms at δ 138.8, δ 135.1, δ 127.1, δ 120.4, δ 118.9, four methines at δ 135.6, δ 133.3, δ 131.4, δ 131.4, one methylene (N-—(CH 2 ) at δ 61.0 and two methyl groups at δ 53.3 (OCH 3 ) and 11.2 (CH 3 vinyl). The structure of each monomer unit was assigned according to HMBC experiment: signals at δ 7.9 and δ 8.0 were assigned to protons of the pyridil group, since a long range correlation to the N-methylene group at δ 61.0 was detected; additionally the last proton display 3 J coupling to the methylester carbonyl at δ 172.2. Besides other important coupling was shown between the singlet at δ 131.4 (C-7) with protons of the methyl group. The low amounts of aromatic and vinyl proton indicated the presence of a symmetric dimeric molecule such as is showed in FIG. 3 . Two structures could be assigned to this molecule, according to the relative orientation of the methylester group (( 3 A and 3 B)( FIG. 3 ), but structure B has a low probability due to steric hindrance.
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The present invention provides colorant compounds and its molecular structural formulas and methods of isolation of the colorant compounds derived from a reaction of Genipa americana genipin and glycine. The novel compounds were obtained from multiple fractioning by chromatography of the reaction resulting material. The molecular structural formulas resulted from 1 H nuclear magnetic resonance spectroscopy, J-Modulation, H—H Correlation Spectroscopy experiments, and other molecular structural tools analysis.
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BACKGROUND OF THE INVENION
The present invention relates to a resin composition comprising ethylene-based polymers or, more particularly, to a resin composition comprising ethylene-based polymers with excellent moldability and capable of giving shaped articles having excellent mechanical properties.
As well known, high-density polyethylenes are unusually prepared by the polymerization using a Ziegler catalyst and the molecular weight of the current products of high-density polyethylene is relatively high as a trend in consideration of the improved mechanical strength of the articles shaped of the polyethylene resin. A problem encountered in the molding works of high-density polyethylene resins having such a high molecular weight is the workability of the resin and, when the polyethylene resin has a narrow molecular weight distribution, the resin is poorly flowable to cause a great decrease in the productivity of the plastic fabrication along with an increase in the power consumption due to the higher pressure on the molten resin under fabrication.
In order to solve the above mentioned problem, several attempts have been made to manufacture a high-density polyethylene resin excellent in the moldability and the mechanical properties of the shaped articles by the methods of melt-blending, multistage polymerization and the like. Unfortunately, none of the attempts has been quite successful in producing a polyethylene resin having moldability suitable for blow molding and inflation molding.
SUMMARY OF THE INVENTION
An object of the present invention is therefor to provide a resin composition comprising ethylene-based polymers and having a good balance between the moldability of the resin composition and the physical properties of the shaped articles thereof freed from the above described problems in the prior art resin compositions.
Thus, the resin composition of the present invention comprises:
(a) from 15 to 90 parts by weight of a homopolymer of ethylene; and
(b) from 85 to 10 parts by weight of a copolymer of ethylene and, preferably, an α-olefin having from 3 to 10 carbon atoms in a molecule,
and is characterized by the parameters of:
(i) an intrinsic viscosity [η] in the range from 2.0 to 5.2 dl/g;
(ii) a density in the range from 0.938 to 0.970 g/cm 3 ;
(iii) a swelling ratio of at least 1.30; and
(iv) a melt index (MI) satisfying the relationships of log MI≧0.81-0.69 [η] and log MT≧1-0.33 log MI, wherein MT being the melt tension.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
As is mentioned above, the polymeric constituent of the inventive resin composition includes two types of the ethylene-based polymers of the components (a) and (b). The component (a) is a homopolymer of ethylene which may be any one of conventional ones but it is preferable that the component (a) is a combination of a homopolymeric polyethylene resin having an intrinsic viscosity [η] in the range from 12 to 25 and another homopolymeric polyethylene resin having an intrinsic viscosity [η] in the range from 0.2 to 1.5. The weight proportion of the former polyethylene resin to the latter should be 1:1 to 10 or preferably, 1:2 to 7.
The component (b) combined with the component (a) above described is a copolymer of ethylene which may be any one of conventional copolymers of ethylene. It is preferable that the copolymer of ethylene as the component (b) is a copolymer of ethylene and an α-olefin having from 3 to 10 or, more preferably, from 3 to 6 carbon atoms in a molecule. Exemplary of such an α-olefin are propylene, butene-1, hexene-1, octene-1 and the like.
The amounts of the components (a) and (b) in the inventive resin composition should be in the range from 15 to 90% by weight or, preferably, from 40 to 70% by weight of the former and from 85 to 10% by weight or, preferably, from 60 to 30% by weight of the latter based on the total amount of these two types of resins. The above mentioned weight ratio of the resins is essential in order to obtain satisfactory physical properties of the articles shaped of the resin composition. For example, the stiffness of the shaped article is decreased when the amount of the component (a) is less than 15% by weight while an amount of the component (a) in excess of 90% by weight is undesirable because of the poor enviromental stress cracking resistance (ESCR).
In addition to the above described limitation in the formulation of the resin components, the resin composition of the present invention should satisfy following requirements.
(i) The intrinsic viscosity [η] thereof should be in the range from 2.0 to 5.2 dl/g or, preferably, from 2.2 to 4.5 dl/g as measured at 135° C. with tetrahydronaphthalene as the solvent. When the value of the intrinsic viscosity is not within the above range, the moldability of the resin composition is extremely poor.
(ii) The density thereof should be in the range from 0.938 to 0.970 g/cm 3 or, preferably, from 0.940 to 0.960 g/cm 3 . Shaped articles of the resin composition having a density smaller than 0.938 g/cm 3 has poor stiffness.
(iii) The swelling ratio should be at least 1.30 or, preferably, at least 1.35 at a shearing velocity of 10.3 sec -1 . When the swelling ratio is smaller than 1.30, no satisfactory pinch-off characteristic can be obtained in the blow-molded article. Further, it is a desirable condition that the ratio of the swelling ratio at a shearing velocity 103 sec -1 (S 103 ) to the swelling ratio at a shearing velocity 10.3 sec -1 (S 10 .3), i.e. S 103 /S 10 .3, is 1.18 or smaller or, preferably, 1.15 or smaller. This is because a resin composition of which the value is larger than 1.18 may decrease the molding adaptability of a metal mold necessitating replacement of the die resulting in decreased productivity of the molding process.
(iv) The intrinsic viscosity [η] and the melt index MI should satisfy the relationship expressed by the equation log MI≧0.81-0.69 [η]. When this relationship is not satisfied, the extrusion rate of the resin composition cannot be sufficiently high in the molding procedure resulting in decreased productivity along with an increase in the power consumption due to the increase in the pressure on the molten resin composition.
(v) The melt index MI and the melt tension MT should satisfy the relationship expressed by the equation log MT ≧1-0.33 log MI. When a resin composition not satisfying this relationship is molded, break sometimes takes place in the parison and the weld strength of the pinchoff portion is decreased along with a decrease of the bubble stability in the inflation molding.
The resin composition of the present invention comprising the ethylene-based polymers can be prepared in a variety of ways. For example, the homopolymeric polyethylene resin and the copolymer of ethylene can be prepared by the methods of multistage polymerization, melt blending and a combination thereof. A preferable way is the method of multistage polymerization or melt blending for the preparation of a resin composition of the ethylene-based polymers composed of from 5 to 23% by weight of a homopolymeric polyethylene (a) having an intrinsic viscosity in the range from 11 to 26 dl/g, another homopolymeric polyethylene (b) having an intrinsic viscosity in the range from 0.2 to 1.6 dl/g and a copolymer of ethylene (c) having an intrinsic viscosity in the range from 1.5 to 5.1 dl/g, in which the ratio of the amount of the homopolymer (b) to the copolymer (c) is in the range from 1:0.5 to 1:1.5.
A more preferable way capable of giving still better results is a method of three-step polymerization for the homopolymer or copolymer of ethylene by use of a binary catalyst composed of (A) a solid catalyst component comprising titanium, magnesium and a halogen and (B) a catalyst component mainly composed of an organoaluminum compound, in which the first step is performed by the sequence of three partial steps including:
(a) a first partial step in which polymerization is performed to produce from 5 to 23% by weight, based on the overall amount of polymerization, of a homopolymer of ethylene having an intrinsic viscosity in the range from 11 to 26 dl/g at a temperature in the range from 50° to 80° C.;
(b) a second partial step in which the polymerization is continued at a temperature in the range from 70° to 100° C. to produce an ethylene homopolymer having an intrinsic viscosity in the range from 0.2 to 1.6 dl/g; and
(c) a third partial step in which the polymerization is further continued at a temperature in the range from 60° to 90° C. to produce a copolymer of ethylene having an intrinsic viscosity in the range from 2.9 to 5.1 dl/g and containing from 2 to 30% by weight of the α-olefin as the comonomer, the sequential order of the partial steps (b) and (c) being reversible according to need, in which the extents of polymerization in the partial steps (b) and (c) should be controlled such that the ratio of the amount of the polymer produced in the partial step (b) to that in the partial step (c) is in the range from 1:0.5 to 1:1.5.
The polymerization catalyst used in the above described method includes (A) a solid catalyst component comprising titanium, magnesium and a halogen as the essential constituents and (B) a catalyst mainly composed of an organoaluminum compound. The solid catalyst component as the component (A) is a composite solid formed by successively or primarily bringing a magnesium compound into contact with a halogen-containing titanium compound or an addition compound thereof with an electron donor and various kinds of known ones can be used for the purpose without particular limitations. Such a composite solid can be prepared, for example, by reacting a magnesium compound with a chlorine-containing titanium compound in a hydrocarbon solvent under agitation.
The magnesium compound usable in the preparation of the component (A) above includes various kinds of the compounds usually used as a carrier of the Ziegler catalysts. Exemplary of such a magnesium compound are magnesium halides such as magnesium chloride, magnesium bromide, magnesium iodide and magnesium fluoride, magnesium hydroxide, magnesium oxide, magnesium sulfate, magnesium carbonates, hydroxymagnesium halides such as hydroxymagnesium chloride, hydroxymagnesium bromide and hydroxymagnesium iodide; magnesium alkoxides such as magnesium methoxide, magnesium ethoxide, magnesium propoxide and magnesium butoxide; alkoxymagnesium halides such as methoxymagnesium chloride, methoxymagnesium bromide, ethoxymagnesium chloride, ethoxymagnesium bromide, propoxymagnesium chloride, propoxymagnesium bromide, butoxymagnesium chloride and butoxymagnesium bromide, allyloxymagnesium, allyloxymagnesium halides such as allyloxymagnesium chloride and allyloxymagnesium bromide and alkylmagnesium halides such as methylmagnesium chloride, methylmagnesium bromide, ethylmagnesium chloride, ethylmagnesium bromide, propylmagnesium chloride, propylmagnesium bromide, butylmagnesium chloride and butylmagnesium bromide as well as mixtures thereof.
Although the above named magnesium compounds can be used as such, it is preferable to use a magnesium compound modified with a halide of silicon and the like. A preferable example of such a modified magnesium compound is that disclosed in Japanese Patent Kokai No. 55-40724 according to which a mixture of a magnesium dialkoxide and magnesium sulfate is modified with silicon tetrachloride and an alcohol.
The halogen-containing titanium compound used for the preparation of the component (A) in combination with the above mentioned magnesium compound may be any one of the compounds of divalent, trivalent or tetravalent titanium. The halogen in the halogen-containing titanium compound can be chlorine, bromine or iodine, of which chlorine is preferred. Particular examples of the halogen-containing titanium compound include titanium tetrachloride TiCl 4 , titanium trichloride TiCl 3 , an adduct of titanium trichloride and aluminum chloride TiCl 3 1/3AlCl 3 , methoxytitanium dichloride CH 3 OTiCl 2 , ethoxytitanium trichloride C 2 H 5 OTiCl 3 , propoxytitanium trichloride C 3 H 7 OTiCl 3 , dipropoxytitanium dichloride (C 3 H 7 O) 2 TiCl 2 , diethoxytitanium dichloride (C 2 H 5 O) 2 TiCl 2 , triethoxytitanium chloride (C 2 H 5 O) 3 TiCl and the like. It is preferable that the solid catalyst component as the component (A) is prepared by combining the magnesium compound and the halogen-containing titanium compound in such a proportion that the molar ratios of halogen/titanium and magnesium/titanium are in the ranges of from 3 to 200 and from 5 to 90, respectively.
The organoaluminum compound as the component (B) is a compound having at least one aluminum-to-carbon linkage in a molecule such as those belonging to the classes of R 3 Al, R 2 AlX, RAlX 2 , R 2 AlOR, RAl(OR)X, R 3 Al 2 X 3 and the like, in which R is an alkyl or aryl group having 1 to 20 carbon atoms while the groups denoted by R in a molecule may be the same ones or different ones when the compound has two or more groups R in a molecule and X is a halogen atom. Exemplary of the particularly preferable organoaluminum compound are diethylaluminum monochloride, diisopropylaluminum monochloride, diisobutylaluminum monochloride, dioctylaluminum monochloride, ethylaluminum dichloride, isopropylaluminum dichloride, ethylaluminum sesquichloride and the like. The organoaluminum compound as the component (B) should be used in an amount by moles of 0.1 to 1000 times of the titanium compound in the component (A).
The catalyst mainly composed of the above described components (A) and (B) usually has a capacity to produce 80 to 400 grams of a polymer of ethylene per milligram of the titanium contained therein.
Among the catalysts of the above described type, particularly suitable for the purpose of the present invention are those described in Japanese Patent Kokai Nos. 54-161691, 55-40724 and 55-149307.
The method for the preparation of the inventive resin composition is performed by the three-step polymerization of ethylene by use of the above described catalyst.
The first step is the above described step (a) which should be performed under a temperature condition of 50° to 80° C. The polymerization reaction cannot proceed to a sufficient extent when the temperature is below 50° C. with resultant low productivity while a reaction temperature higher than 80° C. is undesirable due to the difficulty in controlling the intrinsic viscosity of the polymer obtained by the reaction so that no satisfactory properties cannot be imparted to the homopolymer of ethylene. Furthermore, the reaction in this step (a) is performed under such conditions suitably selected that the homopolymer of ethylene prepared by the reaction may have an intrinsic viscosity [η] in the range from 11 to 26 dl/g or, preferably, from 12 to 24 dl/g. These requirements for the intrinsic viscosity can be satisfied by suitably selecting, in addition to the above mentioned temperature condition, the pressure, feed rates of ethylene and hydrogen and other parameters. In particular, the intrinsic viscosity can readily be controlled within the above given preferable range by use of a molecular weight controlling agent such as hydrogen. When the intrinsic viscosity of the homopolymer of ethylene produced in this stage is smaller than 11 dl/g, on the other hand, the ethylene-based polymer finally obtained may have an unduly small swelling ratio so that the polymer is no longer suitable for blow molding while the polymer should not have an intrinsic viscosity larger than 26 dl/g due to the difficulty encountered in the continuous operation along with the sharkskin-like appearance of the finally shaped article with no practical value.
In addition, the polymerization reaction in this step (a) should be controlled and terminated in such a manner that the amount of the polymer produced in this step is in the range from 5 to 23% by weight or, preferably, from 8 to 20% by weight or, more preferably, from 10 to 17% by weight of the total amount of the polymer produced in the three steps (a), (b) and (c). This condition can be achieved by adequately selecting the polymerization time in accordance with the conditions of the polymerization reaction. When this amount of the polymer is smaller than 5% by weight, the homopolymer or copolymer of ethylene finally obtained may have an unduly small swelling ratio along with decreased miscibility or compatibility between the homopolymers or copolymers produced in the individual steps and difficulties are encountered in the continuous operation of the process due to the decreased bulk density of the polymer. The amount of the polymer produced in this step larger than 23% by weight is also undesirable because of the poor moldability of the polymer finally obtained.
After completion of the above described step (a), the steps (b) and (c) are undertaken, the sequential order of these two steps being reversible. That is, the three steps of (a), (b) and (c) of the polymerization are carried out in the sequential order of either (a), (b) and (c) or (a), (c) and (b). The polymerization reaction in this step (b) is performed under a temperature condition of 70° to 100° C. or, preferably, 75° to 95° C. as is mentioned before. When the temperature in this step (b) is lower than 70° C., the polymerization reaction cannot proceed sufficiently so that the productivity is decreased. When the temperature in this case exceeds 100° C., on the other hand, the polymer already produced is partly melted and clotted so that great difficulties are encountered in the continuous operation. In addition to the above mentioned condition of temperature, the polymerization reaction in this step (b) should be controlled so as to produce a homopolymer of ethylene having specified properties. That is, the conditions of the polymerization reaction in this step should be selected in such a manner that the produced polymer has an intrinsic viscosity in the range from 0.2 to 1.6 dl/g or, preferably, from 0.3 to 1.4 dl/g. The soluble fraction of the homopolymer of ethylene also increases when the intrinsic viscosity of the polymer is smaller than 0.2 dl/g. An intrinsic viscosity of the polymer larger than 1.6 dl/g is, on the other hand, undesirable from the practical standpoint due to the decrease in the flowability and ESCR of the homopolymer of ethylene. It should be noted here that the above described requirements are limitatively relative to the properties of the homopolymer of ethylene produced by carrying out the polymerization with supply of the unreacted ethylene monomer to the step (b) and are not relative to the properties of the homopolymer of ethylene produced by the introduction of a mixture containing the polymer, i.e. a mixture of the monomers, oligomers, homopolymers, after the polymerization reaction proceeded to some extent through the step (a) and, further, step (c). The same remarks are held also for the step (c). Therefore, the conditions in this step (b) can easily and independently selected without being affected by the conditions and the properties of the produced polymer in the step (a). In other words, furthermore, the conditions of the polymerization in the step (b) or step (c) are selected with reference to the properties of the homopolymer produced from the monomers as the starting material and not to define the properties of the homopolymer actually obtained after the step (b) or step (c). Therefore, the conditions of the step (b) can be selected in advance independently from the properties of the polymer produced in the step (a) or in the step (c).
In a similar manner to the selection of the conditions in the step (a), the conditions in this step (b) can readily be established by adequately selecting the parameters such as the reaction pressure, feed rate of ethylene, feed rate of hydrogen and others.
In the next place, the polymerization in the step (c) is performed under the condition of temperature in the range from 60° to 90° C. or, preferably, from 65° to 85° C. When the temperature in this step (c) is lower than 60° C., the polymerization velocity is low not to ensure a sufficiently high productivity while difficulties are encountered in the continuous operation at a temperature higher than 90° C. due to the partial melting of the polymer to form lumps. Further, the conditions of this step (c) should be selected in such a manner that the homopolymer or copolymer of ethylene formed in the step contains the α-olefin other than ethylene in a content of 2 to 15% by weight or, preferably, 4 to 10% by weight and the intrinsic viscosity thereof [η] is in the range from 2.9 to 5.1 dl/g or, preferably, from 3.1 to 4.7 dl/g. Such conditions of the step (c) can be established, similarly to the steps (a) and (b), by adequately selecting the parameters such as the reaction pressure, feed rate of ethylene, feed rate of the α-olefin other than ethylene, feed rate of hydrogen and others. Further, similarly to the steps (a) and (b), the conditions in this step (c) should be selected on the base of the properties of the copolymer formed from the monomers of ethylene and other α-olefins and not on the base of the properties of the homopolymer or copolymer per se actually produced in the step (c) starting from the mixture containing the polymers after the step (a) and further the step (b).
As to the requirements for the copolymer of ethylene to be produced in the above described step (c), the content of other α-olefins such as propylene, butene-1, pentene-1, hexene-1 and the like should preferably be in the range from 2 to 30% by weight since the finally obtained polymer containing less than 2% by weight of the α-olefins may have a decreased ESCR while the finally obtained polymer containing more than 30% by weight of other α-olefins may have a decreased stiffness. Further, the homopolymer or copolymer of ethylene as the product may have a decreased ESCR when the conditions in this step lead to an intrinsic viscosity [η] smaller than 1.5 dl/g while the polymer may have a decreased flowability with poor practical value when the conditions in this step lead to an intrinsic viscosity larger than 5.1 dl/g.
It is optional in the above described method that either the step (b) preceeds the step (c) or vice versa. At any rate, the polymerization in these steps should be performed under control in such a manner that the ratio between the amounts of the polymers formed in the step (b) and in the step (c) is in the range from 1:0.5 to 1:1.5 or, preferably, in the range from 1:0.6 to 1:1.3. A ratio of polymerization outside this range is undesirable because the polymers formed in the steps (b) and (c) have poor compatibility along with an undue increase in the resin pressure.
The type of polymerization in each of the steps of the above described method is not particularly limitative including suspension polymerization, solution polymerization, gas-phase polymerization and the like carried out either batch-wise or as a continuous process. For example, the three-step suspension polymerization can be performed by use of an inert solvent such as pentane, n-hexane, cyclohexane, heptane, benzene, toluene and the like.
The composition of the polymer of ethylene according to the present invention has a sufficiently large melt tension of at least 30 grams along with good moldability. For example, break of the parison in the blow molding does not take place over a long time and the swelling ratio is little dependent on the shearing velocity so that the composition is very versatile characteristically in respect of the conditions for blow molding. The composition also exhibits excellent bubble stability in the inflation molding capable of giving films having good appearance.
Furthermore, the composition of the polymer of ethylene according to the present invention is excellent in the mechanical strengths such as stiffness and the like with an Olsen stiffness of at least 7000 kg/cm 2 . The composition is excellent with an ESCR of at least 200 hours and contains only 5% or smaller of the constituents soluble in organic solvents.
Therefore, the composition of the polymer of ethylene according to the present invention is very useful as a base material of various shaped articles such as films, containers and the like and particularly suitable for blow molding of large articles. When the resin composition of the present invention is prepared by the most preferable method as described above, in addition, an additional advantage is obtained in the process that no degassing vessel is required since the polymerization proceeds under a condition of a decreased supply of hydrogen in the step (a) as the first-step polymerization.
In the following, the present invention is described in more detail by way of examples.
EXAMPLES 1 and 2 and COMPARATIVE EXAMPLES 1 to 5
(1) Preparation of the solid catalyst
In 50 ml of n-heptane were suspended 1.0 gram (g) (8.8 m moles) of magnesium diethoxide and 1.06 g (8.8 m moles) of anhydrous magnesium sulfate purchased on the market and were further added 1.5 g (8.8 m moles) of silicon tetrachloride and 1.6 g (35.2 m moles) of ethyl alcohol and the reaction was carried out at 80° C. for 1 hour. Thereafter, 5 ml (45 m moles) of titanium tetrachloride were added thereto and the reaction was continued at 98° C. for additional 3 hours. After completion of the reaction, the reaction mixture was cooled and kept standing and the supernatant liquid was discarded by decantation followed by three times of washing of the solid by the addition of 100 ml of fresh n-heptane, agitation and standing of the mixture and discarding of the supernatant liquid and finally a dispersion was obtained by the addition of 200 ml of n-heptane to the solid catalyst. The content of titanium supported on the solid was determined colorimetrically to give a result of 42 mg Ti/g carrier.
(2) Preparation of a composition of the copolymer of ethylene
Into a stainless steel-made autoclave were introduced, after replacement of the air inside with dry nitrogen, 500 milliliters (ml) of dehydrated hexane, 0.08 milli mole (m mole) of the solid catalyst prepared as described in (1) above containing 0.21 m mole of triethyl aluminum and 0.59 m mole of diethylaluminum chloride.
In the next place, the autoclave was continuously fed with hydrogen at a rate calculated to give the resultant homopolymer of ethylene an intrinsic viscosity [η] 1 shown in Table 1 and ethylene to give a total pressure of 8.7 kg/cm 2 G inside the reaction vessel to perform the reaction for 25 minutes at 70° C.
Thereafter, the reaction in the second step was performed at 90° C. for 120 minutes so as to obtain a homopolymer of ethylene having an intrinsic viscosity [η] 2 as shown in Table 1. Further, the reaction was continued for 30 minutes at 80° C. by the addition of ethylene and propylene so that the copolymer of ethylene had an intrinsic viscosity [η] as shown in Table 1 with supply of hydrogen.
After completion of the reaction, the composition of the polymer of ethylene was washed, dried and subjected to the measurements of the physical properties to give the results shown in Table 2.
EXAMPLES 3 and 4
The same process of the three-step polymerization as in Example 1 was undertaken excepting the use of a solid catalyst prepared from magnesium diethoxide, silicon tetrachloride, isopropyl alcohol and titanium tetrachloride according to the example of preparation described in Japanese Patent Kokai No. 55-149307. In Example 4, butene-1 was used in place of the propylene in Example 1. The characterization of the compositions of the polymer of ethylene obtained in this manner is shown in Table 1 and the physical properties thereof are shown in Table 2.
COMPARATIVE EXAMPLE 6
The procedure of the polymerization was substantially the same as in Example 1 for the preparation of a composition of the polymer of ethylene except that the intrinsic viscosities [η] of the homopolymer of ethylene produced in the first step, the copolymer of ethylene produced in the second step and the homopolymer of ethylene produced in the third step were 0.6, 4.04 and 20.7, respectively. The characterization of the composition and the physical properties thereof were as shown in Tables 1 and 2, respectively.
EXAMPLE 5
A composition of the polymer of ethylene as shown in Table 1 was prepared by the three-step polymerization in a similar manner to Example 1. The physical properties of this composition are shown in Table 2.
COMPARATIVE EXAMPLE 7
A composition of the polymer of ethylene was prepared in the same manner as in Example 1 except that the polymerization process was performed in a two-step polymerization method. The physical properties of this composition are shown in Table 2.
EXAMPLES 6 to 10 and COMPARATIVE EXAMPLES 8 to 17
(1) Preparation of the solid catalyst
In 50 ml of n-heptane were suspended 1.0 g (8.8 m moles) of magnesium diethoxide and 1.06 g (8.8 m moles) of anhydrous magnesium sulfate purchased on the market and were further added 1.5 g (8.8 m moles) of silicon tetrachloride and 1.6 g (35.2 m moles) of ethyl alcohol and the reaction was carried out at 80° C. for 1 hour. Thereafter, 5 ml (45 m moles) of titanium tetrachloride were added thereto and the reaction was continued at 98° C. for additional 3 hours. After completion of the reaction, the reaction mixture was cooled and kept standing and the supernatant liquid was discarded by decantation followed by three times of washing of the solid by the addition of 100 ml of fresh n-heptane, agitation and standing of the mixture and discarding of the supernatant liquid and finally a dispersion was obtained by the addition of 200 ml of n-heptane to the solid catalyst. The content of titanium supported on the solid was determined colorimetrically to give a result of 42 mg Ti/g carrier.
(2) Preparation of a composition of the copolymer of ethylene
Into a stainless steel-made autoclave of 2 liter capacity were introduced, after replacement of the air inside with dry nitrogen, 500 ml of dehydrated hexane, 0.08 m mole of the solid catalyst prepared as described in (1) above containing 0.16 m mole/liter of titanium, 0.21 m mole of triethyl aluminum and 0.59 m mole of diethyl aluminum chloride.
In the next place, the autoclave was continuously fed with hydrogen at a rate calculated to give the resultant polymer of ethylene an intrinsic viscosity [η] shown in Table 3 and ethylene at a rate to give a total pressure inside the vessel of 8.7 kg/cm 2 G and the reaction was performed with agitation for 25 minutes at a predetermined temperature shown in Table 3.
In the second step to follow, the reaction vessel was cooled to 40° C. and further fed with ethylene, propylene and hydrogen in such a calculated volume that an intrinsic viscosity [η] shown in Table 3 could be obtained and the reaction was performed under a total pressure of 8.3 kg/cm 2 G for 120 minutes with agitation at a predetermined temperature indicated in Table 3.
In the third step, dehydrated hexane was introduced in an additional volume of 500 ml and the reaction was performed with agitation for 30 minutes at a predetermined temperature indicated in Table 3 under a total pressure of 6 kg/cm 2 with supply of ethylene, propylene and butene-1 as well as hydrogen in a volume calculated to give an intrinsic viscosity shown in Table 1.
After completion of the reaction, the copolymeric composition of ethylene thus obtained was washed and dried and then subjected to the measurements of the physical properties to give the results shown in Tables 3 and 4.
EXAMPLE 11
(1) Preparation of the catalyst
A reaction mixture was prepared by adding 5.05 g (38 m moles) of aluminum chloride and 10 g (88 m moles) of magnesium diethoxide into 50 ml of ethyl alcohol. Heat evolution took place by this admixing and refluxing of the ethyl alcohol started. After the reaction performed for 60 minutes under reflux, ethyl alcohol was removed by distillation and the residue was subjected to vacuum-drying at 120° C. for 6 hours and the thus obtained solid material pulverized in a ballmill at room temperature for 60 minutes. A 1 g portion of this powder was suspended in 30 ml of n-heptane and 3 ml of titanium tetrachloride were added to the suspension and reacted at 100° C. for 3 hours. After completion of the reaction, washing of the solid material was repeated three times each with 50 ml of n-heptane followed by the addition of 200 ml of n-heptane to form a suspension of the solid catalyst. The content of titanium in this catalyst was 50 mg Ti/g carrier.
(2) Preparation of the copolymeric composition of ethylene
The procedure was substantially the same as that described in (2) of Examples 6 to 10 excepting the use of the catalyst obtained in (1) above. The results are shown in Tables 3 and 4.
EXAMPLE 12
(1) Preparation of the catalyst
A reaction mixture was prepared by dispersing 10.0 g (88 m moles) of magnesium diethoxide in 150 ml of n-heptane and further adding 1.09 g (11 m moles) of silicon tetrachloride and 1.32 g (22 m moles) of isopropyl alcohol thereto at room temperature and the reaction was performed for 2 hours by heating the mixture at 80° C. Thereafter, 25 ml of titanium tetrachloride were added to the dispersion and the reaction was continued at about 100° C. for additional three hours. After cooling, washing was repeated with n-heptane until no free chlorine ions could be detected followed by final addition of 2 liters of n-heptane to form a suspension of the catalyst component (A). The content of titanium in the solid material of this suspension was 78 mg Ti/g carrier.
(2) Preparation of the copolymeric composition of ethylene
The procedure was substantially the same as that described in (2) of Examples 6 to 10 excepting the use of the catalyst obtained in (1) described above. The results are shown in Tables 3 and 4.
TABLE 1__________________________________________________________________________ Homopolymer of ethylene Copolymer of ethylene [η] Density [η].sub.1 % by wt. [η].sub.2 % by wt. Comonomer [η] % by wt. (dl/g) (g/cm.sup.3)__________________________________________________________________________Example 1 20.0 10 0.3 50 Propylene 4.5 40 3.93 0.954Example 2 18.1 10 0.4 50 Propylene 3.5 40 3.33 0.959Example 3 14.1 14 0.65 48 Propylene 4.51 38 3.86 0.954Example 4 19.3 10 1.3 50 Butene-1 4.0 40 4.10 0.942Comparative 6.2 10 0.6 50 Propylene 2.45 40 1.90 0.955Example 1Comparative 19.5 10 0.8 50 Propylene 7.88 40 5.51 0.949Example 2Comparative 20.1 10 0.9 50 Propylene 3.60 40 3.90 0.935Example 3Comparative -- -- 0.9 50 Propylene 5.94 50 3.43 0.952Example 4Comparative -- -- 1.05 50 Propylene 6.79 50 3.92 0.948Example 5Comparative 20.7 10 0.6 50 Propylene 4.04 40 3.93 0.952Example 6Example 5 17.4 10 1.09 50 Propylene 2.04 40 2.87 0.953Comparative -- -- 0.85 50 Propylene 4.73 50 2.79 0.9555Example 7__________________________________________________________________________ Swelling Ratio of swelling 0.81- 1-0.33 ratio ratio log MI 0.69 [η] log MT log MI__________________________________________________________________________ Example 1 1.42 1.06 -1.68 -1.90 1.62 1.55 Example 2 1.46 1.10 -1.21 -1.49 1.51 1.40 Example 3 1.44 1.08 -1.65 -1.85 1.58 1.54 Example 4 1.41 1.09 -1.70 -2.02 1.66 1.56 Comparative 1.10 1.14 0.36 0.50 0.60 0.88 Example 1 Comparative -- -- -2.52 -2.99 -- 1.83 Example 2 Comparative 1.43 1.06 -1.61 -1.88 1.61 1.54 Example 3 Comparative 1.23 1.06 -1.60 -1.56 1.38 1.53 Example 4 Comparative 1.19 1.07 -1.92 -1.89 1.48 1.63 Example 5 Comparative 1.29 1.22 -1.62 -1.90 1.46 1.53 Example 6 Example 5 1.60 1.13 -0.70 -1.17 1.38 1.23 Comparative 1.36 1.04 -0.60 -1.12 1.18 1.20 Example 7__________________________________________________________________________ [η]: measured at 135° C. in decahydronaphthalene Swelling ratio: capillary rheometer; orifice D = 0.06 inch and L = 2 inches; temperature 190° C.; shearing velocity 10.3 sec.sup.-1 ; spontaneous cooling of 5 cm strand; calculated as the ratio of (diameter of test piece)/(diameter of nozzle) ##STR1## MI: measured according to ASTM D 1238 MT: melt tension; melt tension tester manufactured by Toyo Seiki Co.; orifice D = 2.10 mm and L = 8.00 mm; temperature 190° C.; plunger descending at 15 mm/minute; takeup velocity of strand 10 r.p.m.
TABLE 2__________________________________________________________________________ Rate of Resin Blow- Time to parison Ratio of parison Olsen stiffness extrusion pressure mold- Babble break (seconds) diameter (Kg/cm) (g/min) (Kg/cm.sup.2 G) ability Stability__________________________________________________________________________Example 1 110 1.03 10500 38 80 Good GoodExample 2 40 1.06 9400 39 70 Good GoodExample 3 105 1.04 10600 37 86 Good GoodExample 4 123 1.05 8100 37 84 Good GoodComparative Not moldable 10900 30 50 Poor NotExample 1 moldableComparative Not moldable 9500 -- -- Poor NotExample 2 moldableComparative 105 1.06 6100 35 91 Good GoodExample 3Comparative 53 1.03 10200 34 112 Good PoorExample 4Comparative 72 1.04 9300 29 129 Good PoorExample 5Comparative 57 1.25 10200 37 87 Good SlightlyExample 6 swayingExample 5 15 1.08 10500 40 54 Good GoodComparative 5 1.03 10900 39 65 Good PoorExample 7__________________________________________________________________________ Time to parison break: time to the break of 40 g parison at 215° C.; die diameter 10 mm; core diameter 9 mm Ratio of parison diameter: (parison diameter at extrusion velocity 60 r.p.m.)/(parison diameter at extrusion velocity 20 r.p.m.) Olsen stiffness: measured according to ASTM D 747 Amount of extrusion: extruded amount per minute at screw rotation 60 r.p.m. using 20 mm diameter inflation molding machine Resin pressure: pressure of resin under the same conditions as above Bubble stability: stability of bubbles by inflation molding at extrusion rate of 22 g/minute using 20 mm diameter inflation molding machine Blow moldability: possibility or impossibility of blow molding of bottles using 25 mm diameter blow molding machine
TABLE 3__________________________________________________________________________ First step Second step** Tem- Tem- Third step** per- Intrinsic Amount per- Other α-olefin Intrinsic Temper- Other α-olefin ature viscosity polymerized ature Content viscosity ature Content (°C.) [η]* (dl/g) (% by wt.) (°C.) Kind (% by wt.) [η]* (dl/g) (°C.) Kind (% by__________________________________________________________________________ wt.)Example 6 70 20.1 10.0 90 -- -- 0.32 80 Propylene 16.8Example 7 70 17.8 10.0 90 -- -- 0.38 80 Propylene 16.8Example 8 70 19.4 10.0 90 -- -- 1.31 80 Butene-1 17.8Example 9 70 14.1 14.3 90 -- -- 0.41 80 Propylene 17.2Example 10 70 13.8 17.0 90 -- -- 0.65 80 Propylene 17.9Example 11 70 19.1 10.0 90 -- -- 1.05 80 Propylene 16.3Example 12 70 18.1 10.0 80 Propylene 16.3 3.5 90 -- --Comparative 90 0.6 50.0 80 Propylene 16.8 4.04 50 -- --Example 8Comparative 70 10.5 14.3 90 -- -- 0.85 80 Propylene 17.3Example 9Comparative 70 28.0 4.3 90 -- -- 1.1 80 Propylene 15.8Example 10Comparative 70 15.1 25.0 90 -- -- 1.1 80 Propylene 22.5Example 11Comparative 70 19.3 10.0 90 Propylene 5.4 1.05 80 Propylene 8.8Example 12Comparative 70 18.5 10.0 90 -- -- 0.2 80 Propylene 17.8Example 13Comparative 70 18.7 10.0 90 -- -- 1.7 80 Propylene 16.8Example 14Comparative 70 18.4 10.0 90 -- -- 0.93 80 Propylene 1.8Example 15Comparative 70 19.2 10.0 90 -- -- 1.12 80 Propylene 45.0Example 16Comparative 70 18.5 10.0 90 -- -- 0.91 80 Propylene 18.0Example 17__________________________________________________________________________ Third step** (c)/(b) Final polymer Intrinsic ratio of Intrinsic Ratio of viscosity polymerized Density viscosity Swelling swelling 0.81- 1-0.33 [η]* (dl/g) amounts (g/cm.sup.3) [η]* (dl/g) ratio ratio log MI 0.69 [η] log log__________________________________________________________________________ MIExample 6 4.41 0.8 0.954 3.93 1.42 1.06 -1.68 -1.90 1.62 1.55Example 7 3.46 0.8 0.949 3.33 1.46 1.10 -1.21 -1.49 1.51 1.40Example 8 3.96 0.8 0.942 4.10 1.44 1.09 -1.70 -2.02 1.66 1.56Example 9 4.39 0.8 0.954 3.86 1.44 1.07 -1.57 -1.85 1.58 1.51Example 10 4.51 0.7 0.948 4.20 1.42 1.09 -1.80 -2.09 1.64 1.59Example 11 3.99 0.8 0.951 4.03 1.44 1.05 -1.66 -1.97 1.65 1.55Example 12 1.27 0.8 0.952 3.70 1.46 1.08 -1.74 -1.74 1.59 1.57Comparative 20.7 0.25 0.952 3.93 1.29 1.22 -1.62 -1.90 1.46 1.53Example 8Comparative 5.29 0.3 0.951 3.92 1.28 1.10 -1.77 -1.89 1.45 1.58Example 9Comparative 4.57 0.3 0.950 3.72 1.38 1.13 -1.68 -1.76 1.56 1.55Example 10Comparative 3.1 0.3 0.941 6.49 not not not -3.67 not notExample 11 measurable measurable measur- measur- measur- able able ableComparative 3.26 0.3 0.951 3.76 1.46 1.07 -1.68 -1.77 1.58 1.55Example 12Comparative 4.78 0.3 0.949 3.86 1.42 1.08 -1.66 -1.85 1.58 1.55Example 13Comparative 2.81 0.3 0.950 3.84 1.43 1.14 -1.86 -1.84 1.57 1.61Example 14Comparative 3.94 0.3 0.964 3.88 1.42 1.08 -1.66 -1.87 1.60 1.55Example 15Comparative 2.6 0.3 0.937 3.52 1.47 1.10 -1.60 -1.62 1.53 1.53Example 16Comparative 7.99 0.3 0.949 5.5 not not -2.52 -2.99 not 1.83Example 17 measur- measur- measur- able able able__________________________________________________________________________ *Measurement was performed at 135° C. in decahydronaphthalene. **In Examples 6 to 11, the steps (b) and (c) were undertaken as the secon and third steps, respectively. In Example 12, the order of the step (b) and the step (c) was reversed.
TABLE 4__________________________________________________________________________ Olsen*.sup.1 Soluble*.sup.5 stiffness Melt tension ESCR*.sup.4 fraction Appearance of (Kg/cm) (g)*.sup.2 Swelling ratio*.sup.3 (hr) (%) shaped article Remarks__________________________________________________________________________Example 6 10500 42 1.42 400 4 Good --Example 7 9700 32 1.46 300 4 Good --Example 8 8400 46 1.44 1000< 3 Good --Example 9 10600 38 1.44 500 4 Good --Example 10 10100 36 1.42 300 3 Good --Example 11 10200 43 1.44 600 3 -- --Example 12 10300 39 1.46 350 2 -- --Comparative 10200 29 1.29 400 4 -- --Example 8Comparative 10000 28 1.28 1000< 3 -- --Example 9Comparative 9800 36 1.38 450 3 lumps, sharkskin poor extractionExample 10 of polymer after 36 hoursComparative 8500 not measurable not measurable 1000< 2 not moldable --Example 11Comparative 10100 38 1.46 200 15 -- --Example 12Comparative 9700 38 1.42 650 10 -- --Example 13Comparative 9900 39 1.43 25 2 lumps --Example 14Comparative 13200 40 1.42 50 3 -- --Example 15Comparative 6500 34 1.47 1000< 3 lumps --Example 16Comparative 9500 not measurable not measurable 1000< 3 -- --Example 17__________________________________________________________________________ *.sup.1 measured according to ASTM D 747 *.sup.2 melt tension tester manufactured by Toyo Seiki Co.; orifice D = 2.10 mm and L = 8.00 mm; temperature 190° C.; plunger descending a 15 mm/minute; takeup velocity of strand 10 r.p.m. *.sup.3 capillary rheometer; orifice D = 0.06 inch and L = 2 inches; temperature 190° C.; shearing velocity 10.3 sec.sup.-1 ; spontaneous air cooling of 5 cm strand; calculated as the ratio of (diameter of test piece)/(diameter of nozzle) *.sup.4 3 mm; measured by Bell method using 10% aqueous solution of Nissa Nonion *.sup.5 extraction of 10 g sample with 100 ml of hexane in a Soxhlet extractor
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The invention provides a novel resin composition of polymers of ethylene capable of giving a shaped article having outstandingly excellent mechanical properties but yet having very good processability or moldability. The resin composition is composed of 15-90% by weight of a homopolymer of ethylene and 85-10% by weight of a copolymer of ethylene and characterized by several parameters including the intrinsic viscosity, density and swelling ratio as well as satisfaction of the relationships between the melt index and the intrinsic viscosity and between the melt index and the melt tension expressed by the respective logarithmic equations. Industrially feasible processes for the preparation of such resin compositions are described in detail.
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BACKGROUND OF THE INVENTION
The invention relates to an extracorporeal blood chamber, to an extracorporeal blood line and to an apparatus for treatment of extracorporeal blood.
In particular the extracorporeal blood chamber is for air/liquid separation and/or for the mixing of two liquids, for example blood and an infusion liquid.
Specifically, though not exclusively, the invention can be usefully applied in a hemo(dia)filtration system for mixing extracorporeal blood with a replacement fluid.
U.S. Pat. No. 5,605,540 describes an extracorporeal blood chamber provided with an expansion chamber having on a bottom thereof a first and a second access and at the top thereof at least a third access; the blood chamber is further provided with a first and a second conduit, terminating respectively in the first and second accesses, and with a third conduit terminating in the first conduit. In use the first and the second conduit transport blood, while the third conduit transports an infusion liquid.
U.S. Pat. No. 4,681,606 describes an extracorporeal blood chamber provided with an expansion chamber having at a bottom thereof a first access, on a side thereof a second access, and at a top thereof two further accesses; the blood chamber also has a first and a second conduit terminating respectively in the first and the second access. In use the first and the second conduit transport blood, while one of the top accesses is connected to an injection tube.
U.S. Pat. No. 5,591,251 describes an extracorporeal blood chamber provided with an expansion chamber having at a bottom thereof a first access, on a side thereof a second access, and at a top thereof another two accesses; the blood chamber further has a conduit terminating in the first lateral access. In use the first and the second access are for the passage of blood, while one of the top accesses is for passage of an infusion liquid.
U.S. Pat. No. 4,666,598 describes an extracorporeal blood chamber provided with an expansion chamber having on a bottom thereof a first access and on a side thereof a second access; the blood chamber also has a first conduit terminating in the first access, a second conduit terminating in the second access, and a third conduit terminating in the first conduit. In use the first and the second conduits transport blood, while the third conduit transports an infusion liquid.
The prior-art extracorporeal blood chambers can be improved upon in relation to the effectiveness of the mixing between the blood and the infusion liquid, especially in the case of a hemo(dia)filtration treatment with mixing between the blood and the replacement liquid upstream of the hemo(dia)filter (pre-dilution). In a case of pre-dilution the effectiveness of the hemo(dia)filtration treatment depends on the degree of mixing between the blood and the replacement liquid at the inlet of the hemo(dia)filter.
SUMMARY OF THE INVENTION
An aim of the present invention is to provide an extracorporeal blood chamber with which very good mixing results of the blood with an infusion liquid can be obtained.
A further aim of the invention is to realise an extracorporeal blood line comprising the above-mentioned blood chamber.
A further aim of the invention is to provide an apparatus for extracorporeal blood treatment comprising the above-cited blood line.
An advantage of the invention is that it provides an extracorporeal blood chamber which is able efficiently to separate the air from the liquid, in particular the air contained in the infusion liquid.
A further advantage is that it makes available an extracorporeal blood chamber which reduces to a minimum the turbulence in the blood flow in the case of absence of infusion liquid flow, i.e. when the blood is not mixed with the liquid.
A still further advantage is that the extracorporeal blood chamber is compact and small.
The aims and more besides are all attained by the invention, as it is characterised in one or more of the appended claims.
Further characteristics and advantages of the present invention will better emerge from the detailed description that follows, of at least an embodiment of the invention, illustrated by way of non-limiting example in the figures of the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
The description will be made herein below with reference to the appended figures of the drawings, provided by way of non-limiting example, in which:
FIG. 1 is a diagram of the hemo(dia)filtration apparatus of the invention;
FIG. 2 is a front view of an apparatus made according to the diagram of FIG. 1 , and applied operatively to the front panel of a machine for dialysis;
FIG. 3 is a perspective view from behind of the apparatus of FIG. 2 , with some parts removed better to evidence others;
FIG. 4 is a perspective view from the front of FIG. 3 ;
FIG. 5 is a perspective view from behind of the infusion module of the apparatus of FIG. 3 , with some parts removed and other parts added with respect to FIG. 3 ;
FIG. 6 is a view from the front of FIG. 5 ;
FIG. 7 is a front view of a component of the infusion module of FIG. 3 which includes the blood chamber 12 in which the mixing between the blood and the infused liquid takes place;
FIG. 8 is a view from behind of FIG. 7 ;
FIG. 9 is a view from above of FIG. 7 ;
FIG. 10 is a view from below of FIG. 7 ;
FIG. 11 is a view from the left of FIG. 7 ;
FIGS. 12 , 13 , 14 and 15 are sections according respectively to lines XII, XIII, XIV and XV of FIGS. 7 , 8 and 11 .
DETAILED DESCRIPTION
With reference to FIG. 1 , 1 denotes in its entirety an extracorporeal blood treatment apparatus destined for coupling to a machine is for extracorporeal blood treatment able to provide a treatment fluid. In the following description the extracorporeal blood treatment apparatus will be called a hemo(dia)filtration apparatus 1 , the extracorporeal blood treatment machine will be called a dialysis machine and the treatment fluid will be called dialysis fluid, without any more generalised references being lost by use of this terminology. In particular the dialysis machine produces on-line a dialysis fluid of predetermined chemical composition (for example by mixing water and solid and/or liquid concentrates). The dialysis machine is able to reduce the concentration of endotoxins in the dialysis fluid (for example by passage of dialysis fluid through one or more stages of ultrafiltration). The dialysis machine is able to provide a control system of patient weight loss during the treatment (for example by a control of the difference between the dialysis fluid delivery at the inlet and outlet of the blood treatment device thanks to the use of two pumps arranged before and after the blood treatment device—hereinafter hemo(dia)filter—and of two flow-meters arranged before and after the hemo(dia)filter). The hemo(dia)filtration apparatus 1 can be composed, all or in part, by disposable elements. The dialysis machine (of which the front panel is partially illustrated in FIG. 2 ) is of known type, is provided with a fresh dialyser fluid port 2 (see the diagram of FIG. 1 ), from which the dialysis fluid to be introduced in the hemo(dia) filter is taken, an exhausted fluid port 3 , in which the fluid exiting the hemo(dia)filter is discharged (made up of used dialysis fluid and/or of ultrafiltrate), and an on-line port 4 from which the dialysis fluid, to be processed for use as replacement fluid in hemo(dia)filtration treatment, is taken. The dialysis machine is further provided with a system of known type and not illustrated, for preparation of the dialysis fluid; this system is connected to a main dialysis fluid supply line, which terminates in the fresh dialysate port 2 . A secondary dialysis fluid supply line, which branches from the main supply line, terminates in the on-line port 4 . The dialysis machine is further provided with an exhausted liquid discharge line which originates at one end at the exhausted liquid port 3 and which terminates at the other end thereof in a drainage (of known type and not illustrated). When the hemo(dia)filtration apparatus 1 is used as a hemofiltration apparatus 1 , the fresh dialysate port 2 is closed, or non-operative, or, in a further embodiment, absent.
The hemo(dia)filtration apparatus 1 comprises the hemo(dia)filter 5 having a blood chamber and a fluid chamber (not illustrated) which are separated from one another by a semipermeable membrane (not illustrated) which, in this case, comprises a bundle of hollow fibres. In this embodiment the blood chamber comprises the space internally of the hollow fibres, while the fluid chamber comprises the space externally of the hollow fibres. The fluid chamber is further at least partially defined by the tubular body containing the bundle of hollow fibres. The hemo(dia)filtration apparatus 1 comprises an extracorporeal blood circuit having an arterial line 6 , or a blood removal line from the patient for the blood to be treated in the hemo(dia)filter 5 , and a venous line 7 , or patient return line for the blood treated in the hemo(dia)filter 5 . The hemo(dia)filtration apparatus 1 further comprises a blood pump 8 for circulation of blood in the extracorporeal circuit. The blood pump 8 is of a tube-deforming rotary type (peristaltic). The extracorporeal blood circuit further comprises the blood chamber of the hemo(dia)filter 5 . The arterial line 6 comprises an arterial patient end 9 , a pre-pump arterial expansion chamber 10 , a blood pump tube tract 11 , a post-pump arterial expansion chamber 12 , an arterial device end 13 . The venous line 7 comprises a venous device end 14 , a venous expansion chamber 15 , a venous patient end 16 . The dialysis machine is provided with an arterial clamp 17 operating on the arterial line 6 , in particular between the patient arterial end 9 and the pre-pump arterial expansion chamber 10 . The dialysis machine is provided with a venous clamp 18 operating on the venous line 7 , in particular between the patient venous end 16 and the venous expansion chamber 15 . The patient arterial end 9 , like the patient venous end 16 , is designed for connection (directly or via a vascular access device of known type) with a vascular access of a patient. The arterial clamp 17 , respectively the venous clamp 18 , serves for closing a squeezable tract of the arterial line 6 , respectively of the venous line 7 , on command of a control unit of the dialysis machine. The pre-pump arterial expansion chamber 10 , which is arranged downstream of the arterial clamp 17 (where “downstream” means with reference to the blood circulation direction during the treatment), serves for separating the air contained in the blood and for monitoring the arterial blood pressure (before the blood pump 8 ). The venous expansion chamber 15 , which is arranged upstream of the venous clamp 18 (where “upstream” means with reference to the blood circulation direction during the treatment), is for separating the air contained in the blood and for monitoring the venous blood pressure. The pre-pump arterial expansion chamber 10 , like the venous expansion chamber 15 , is designed to give rise to a liquid level separating a lower part full of liquid (blood) from an upper part full of gas (air). Each of the expansion chambers 10 and 15 is provided, for example superiorly, with a zone predisposed for pressure reading; this zone comprises, in the specific case, a membrane device, of known type, having a deformable elastic membrane with an internal surface in contact with the fluid (blood and/or air) contained in the chamber and an external surface operatively associable to a pressure sensor of the dialysis machine. The blood pump tube tract 11 , which is designed for removably coupling with the blood pump 8 , is open-ring conformed (in the specific embodiment it is U-shaped with a horizontal lie and with the convexity facing right, with reference to the viewpoint of a user situated in front of the front panel of the dialysis machine) with two ends, one for blood inlet and the other for blood outlet, fluidly and mechanically connected to two tubular extensions 19 ( FIG. 2 ) solidly connected to the pre-pump arterial expansion chamber 10 . The arterial device end 13 and the venous device end 14 are designed for removably coupling with an inlet port (in the specific embodiment, upper) and, respectively, an outlet port (in the specific embodiment, lower) of the blood chamber of the hemo(dia)filter 5 . The pre-pump arterial expansion chamber 10 and the venous expansion chamber 15 are integrated in a cartridge structure of known type.
The post-pump arterial expansion chamber 12 is inserted in the arterial line 6 between the blood pump 8 and the hemo(dia)filter 5 . The post-pump arterial expansion chamber 12 comprises a blood inlet port 20 , an infusion fluid inlet port 21 (in the present example of hemo(dia)filtration with pre-dilution, the infusion fluid, or infusate, can be replacement fluid, or substituate; in the following description the specific term “replacement fluid” and “substituate” will be used instead of more general terms like “infusion fluid” and “infusate”, without the generalised meaning being compromised), a mixing zone where the blood and replacement fluid are mixed, and an outlet port for the blood-fluid mixture 22 (where the replacement fluid is present in the mixture in case of pre-dilution and absent in case of no pre-dilution).
The post-pump arterial expansion chamber 12 serves to separate the air contained in the replacement fluid. The post-pump arterial expansion chamber 12 monitors the pressure in the replacement fluid supply line. The post-pump arterial expansion chamber 12 also serves to further separate the air contained in the blood along the arterial line 6 downstream of the blood pump 8 and for monitoring the blood pressure in the arterial line 6 between the blood pump and the hemo(dia)filter 5 . The post-pump arterial expansion chamber 12 is designed to produce a liquid level that separates a lower part which is full of liquid (blood or blood/replacement fluid mixture) and an upper part which is full of gas (air). The post-pump arterial expansion chamber 12 is provided, for example superiorly, with a zone predisposed for pressure detection; this zone comprises, in the present embodiment, a membrane device 58 , of known type, having a deformable membrane with an internal surface in contact with the fluid contained in the chamber and an external surface which is operatively associable to a pressure sensor of the dialysis machine. The post-pump arterial expansion chamber 12 will be described in greater detail herein below.
The hemo(dia)filtration apparatus 1 comprises a replacement fluid supply line 23 which provides, in this embodiment, the replacement fluid (substituate) to the extracorporeal blood circuit. The supply line 23 takes the dialysis fluid from the on-line port 4 and, after an ultrafiltration treatment to make it suitable as a replacement fluid, conveys it to the extracorporeal blood circuit.
The supply line 23 branches out from a main branch 24 into a pre-dilution branch 25 fluidly connected to the arterial line 6 and a post-dilution branch 26 fluidly connected to the venous line 7 . The replacement fluid supply line 23 comprises an inlet end 27 having a connector for removable connection with the on-line port 4 for sourcing the dialysis fluid supplied by the dialysis machine. Alternatively to an on-line port of a machine for dialysis fluid preparation, other fluid sources can be used, for example a ready-prepared dialysis fluid or replacement fluid recipient, or a centralised dialysis fluid supply system, supplying to various units.
The replacement fluid supply line 23 comprises an ultrafilter 28 predisposed fluidly in the main branch 24 upstream of the branch-out for ultrafiltering the dialysis fluid taken from the dialysis machine to render the fluid suitable for use as a replacement fluid. The ultrafilter 28 reduces the endotoxin percentage in the fluid. The ultrafilter 28 comprises a semipermeable membrane that separates a first chamber containing the fluid to be ultrafiltered (dialysis fluid) from a second chamber containing the ultrafiltered fluid (replacement fluid). The semipermeable membrane comprises, in the present embodiment, a bundle of hollow fibres. The first chamber of the fluid to be ultrafiltered comprises the inside of the hollow fibres, while the second chamber of the ultrafiltered fluid is defined between the outside of the hollow fibres and the tubular body enclosing the bundle of hollow fibres.
The ultrafilter 28 is further provided, for example superiorly, with a vent line of the air communicating with the first chamber of the fluid to be ultrafiltered and having a clamp (for example manually activated) for intercepting and a vent into the atmosphere protected by a protection device (for example a hydrophobic membrane).
The replacement fluid supply line 23 can further comprise a check valve predisposed fluidly in the main branch 24 upstream of the branch-out. The check valve, which in the present embodiment is not present, might be located after the ultrafilter 28 .
A tract of the replacement fluid pump tube 29 is predisposed in the supply line 23 for coupling with a replacement fluid circulation pump 30 . In to the present embodiment the replacement fluid pump 30 is a tube-deforming rotary pump (peristaltic). The replacement fluid pump tube tract 29 is open-ring shaped with an aspiration end and a delivery end. In particular the replacement fluid pump tube tract 29 is U-shaped, and, in the use configuration with the pump 30 , lies on a vertical plane, with the two end branches arranged horizontally (the convexity of the U is directed oppositely to the blood pump tube tract 11 , i.e. in the present embodiment to the left with reference to the viewpoint of a user situated in front of the front panel of the machine). The rotation axes of the two rotary pumps 8 and 30 are parallel to one another. The pump tube tract 29 , in the engaged configuration with the pump 30 , is arranged symmetrically to the blood pump tube tract 11 , with respect to a plane of symmetry (in the present embodiment, vertical) which is parallel to the rotation axes of the two rotary pumps 8 and 30 . The replacement fluid pump tube tract 29 is fluidly arranged in the main branch 24 upstream of the branch-out (where “upstream” means in reference to the circulation direction of the replacement fluid). The replacement fluid pump tube tract 29 is arranged fluidly upstream of the ultrafilter 28 .
The replacement fluid supply line 23 comprises an auxiliary connection 31 fluidly arranged after the ultrafilter 28 . This auxiliary connection 31 is branched out from the replacement fluid line 23 . The auxiliary line is further provided with a clamp 32 (for example a manually operated clamp) for closing the auxiliary line, and a protection hood for removable closure of the auxiliary line 31 . The auxiliary line branches off from the main branch 24 before the branch-out.
The auxiliary connection 31 is designed for removable fluid connection with the extracorporeal blood circuit, in particular with the arterial line 6 or the venous line 7 . The auxiliary connection 31 serves to fill the extracorporeal circuit with the replacement fluid, in particular during the circuit priming stage, i.e. during the stage preliminary to the treatment during which the air and any other undesirable particles contained in the blood circuit are evacuated and the circuit is filled with an isotonic liquid, for example a saline solution coming from a bag or, as in the present embodiment, with an isotonic fluid (dialysis fluid or saline) which is prepared by the dialysis machine, supplied to the on-line port 4 of the machine and ultrafiltered by crossing the replacement fluid supply line 23 . In the present embodiment the auxiliary connection 31 is removably couplable to the patient end of the arterial line 9 or to the patient end of the venous line 16 . The auxiliary connection 31 comprises, for example, a female luer connector couplable to a is male luer connector at the patient arterial 9 or venous 16 end.
At least one from among the three above-mentioned expansion chambers (arterial pre-pump 10 , arterial post-pump 12 and venous 15 ) is fluidly connected, in particular directly, to the pre-dilution branch 25 or the post-dilution branch 26 . In the present embodiment the post-pump arterial expansion chamber 12 is fluidly connected directly to the pre-dilution branch 25 .
The post-dilution branch 26 opens (directly) into a point of venous line 7 comprised between the hemo(dia)filter 5 and the venous chamber 15 . The venous chamber 15 therefore indirectly communicates, via a tract of venous line 7 , with the post-dilution branch 26 .
The aspiration and delivery ends of the replacement fluid pump tube tract 29 are rigidly connected to at least one from among the above-mentioned expansion chambers (arterial pre-pump 10 , arterial post-pump 12 and venous 15 ). In the present embodiment the aspiration and delivery ends of the replacement fluid pump tube tract 29 are connected rigidly to the post-pump arterial expansion chamber 12 . As mentioned, the expansion chamber bearing the replacement fluid pump tube tract 29 , i.e. the chamber 12 , is provided with a zone for monitoring the pressure which is predisposed for connection with a pressure sensor provided on the dialysis machine. This monitoring zone is provided with the pressure detecting device 58 .
Two tubular extensions for fluid and mechanical connection of the two ends of the pump tube tract 29 are solidly connected (for example are made in a single piece with the chamber itself) to the chamber 12 . The two tubular extensions are not fluidly connected to the chamber 12 , if not indirectly through other parts (for example the ultrafilter 28 ) of the fluid circuit transporting the replacement fluid.
The replacement fluid supply line 23 comprises a fluid communication system which is interpositioned fluidly between the delivery end of the replacement fluid pump tube tract 29 and the expansion chamber bearing the replacement fluid pump tube tract 29 (as mentioned in this case the expansion chamber bearing the pump tube tract 29 is the post-pump arterial expansion chamber 12 ). This fluid communication system comprises is one or more from the following elements: the ultrafilter 28 , the check valve (if present), the branch-out, and at least a tube tract which is flexible and closable by elastic deformation, in particular squeezing.
In the present embodiment, the fluid communication system, which places the replacement fluid pump tube tract 29 in communication with the extracorporeal blood circuit, comprises a first flexible tube 41 having a first end connected with a first tubular connection 42 which is rigidly connected to (but not fluidly communicating with) the post-pump arterial chamber 12 (the first tubular connection 42 is arranged inferiorly of the chamber 12 itself), and a second end which is opposite the first end and connected to a second tubular connection 43 for inlet of the ultrafilter 28 (the second tubular connection 43 for inlet is located inferiorly of the ultrafilter 28 and communicates with the chamber of the fluid to be ultrafiltered). Each of these tubular connections 42 and 43 faces downwards, with reference to an operative configuration of the apparatus 1 . Each of these tubular connections 42 and 43 has a longitudinal axis which extends, at least prevalently, in a vertical direction.
The above-described fluid communication system comprises the ultrafilter 28 and a second three-way flexible tube 44 having a first end which is connected to a tubular connection for outlet of the ultrafilter 28 (the tubular outlet connection is located on a side of the ultrafilter 28 itself, in particular superiorly, and communicates with the ultrafiltrate fluid chamber, i.e. with the outside of the hollow fibres), a second end (arranged superiorly and facing upwards) to which the auxiliary connection 31 is connected by means of the auxiliary line, and a third end (arranged inferiorly and facing downwards).
The above-mentioned three ends of the second flexible tube 44 are in reciprocal fluid communication (for example with reciprocal T or Y arrangement). The second three-way flexible tube 44 , which in the present embodiment is T-shaped with the first end arranged at 90° to the other two, is press-formed by injection of a soft plastic material.
The fluid communication system comprises a third three-way flexible tube 45 having a first end which is connected to the third end of the second flexible tube 44 , a second end connected to the inlet port 21 of the replacement fluid to the chamber 12 , and a third end connected to a zone of the venous line 7 arranged upstream of the venous expansion chamber 15 . In the present embodiment the first end is arranged superiorly (facing upwards), the third end is arranged inferiorly (facing downwards), while the second end is arranged obliquely (facing upwards) with respect to the other two, forming an angle which is less than a right-angle with the first upper end. The third three-way flexible tube 45 is made by press-forming by injection of a soft plastic material. The third three-way flexible tube 45 exhibits the branch-out in the pre-dilution branches 25 and the post-dilution branches 26 , which comprise two of the three ways of the third flexible tube 45 (in particular the ways that exhibit the second and third ends).
The hemodiafiltration apparatus 1 is made in two distinct modules which are fluidly connected one to the other. A first module A (on the right in FIG. 2 ) comprises an initial tract of arterial line 6 which goes from the patient arterial end 9 to the pre-pump expansion chamber 10 . The first module A further comprises the pre-pump expansion chamber 10 , the blood pump tube tract 11 and the venous expansion chamber 15 (integrated with the chamber 10 in the cartridge structure of known type). The first module A further comprises a final tract of venous line 7 which goes from the venous expansion chamber 15 to the patient venous end 16 . The first module A also comprises a tract of arterial line 6 which is arranged downstream of the blood pump 8 and which is integrated into the cartridge body structure. As mentioned, the cartridge structure, which incorporates the chambers 10 and 15 , supports the two ends, aspiration and delivery, of the blood pump tube tract 11 .
A second module B (on the left in FIG. 2 ) comprises the replacement fluid supply line 23 (starting from the inlet end 27 , and including the replacement fluid pump tube tract 29 , the ultrafilter 28 and the pre-dilution and post-dilution branches 25 and 26 ). The second module B further comprises the post-pump arterial expansion chamber 12 . Also included are an intermediate tract of arterial line 33 which fluidly connects an arterial outlet of the first module A (connected to an outlet of the blood pump tube tract) with an arterial inlet of the second module B (connected to the blood inlet of the post-pump arterial expansion chamber), and an intermediate tract of venous line 34 which fluidly connects a venous outlet of the second module B (connected with the post-dilution branch 26 ) with a venous inlet of the first module A (connected with an inlet of the venous expansion chamber).
The second module B comprises a support element to which the supply line of the replacement fluid 23 is constrained in order that the pre-dilution 25 and post-dilution branches 25 and 26 are positioned in a prefixed position with respect to the post-pump arterial expansion chamber. The correct and stable positioning of the pre-dilution and post-dilution branches 25 and 26 with respect to the front panel of the dialysis machine enables operatively efficient use of the above-said branches with two control valves, a pre-dilution control valve 52 and a post-dilution control valve 53 arranged on the front panel.
The support element comprises, in the present embodiment, one or more extensions 35 which emerge from the expansion chamber which bears the replacement fluid pump tube tract 29 (i.e. the post-pump arterial chamber 12 ). The extensions 35 emerge from a side of the chamber 12 located on the opposite side with respect to the replacement fluid pump tube tract 29 and extend in an opposite direction with respect to the extension of the pump tract 29 itself. The extensions 35 , in the present embodiment, are rigidly connected to the chamber 12 that bears the replacement fluid pump tube tract 29 . The extensions 35 , in the present embodiment, are made (for example by press-forming of plastic material) in a single piece with the chamber 12 itself. The support element further comprises a casing 36 engaged to one or more of the extensions 35 . The casing 36 in the present embodiment is joint-coupled to one or more of the extensions 35 . In particular the casing 36 is coupled to one or more of the extensions 35 in at least two joint zones. The casing 36 , made of plastic material, is provided with a front part which at least partially contains the tubular body of the ultrafilter 28 .
One of the extensions 35 exhibits a mounting extension 37 which, in collaboration with the two tubular extensions 38 for engagement of the ends of the replacement fluid pump tube tract 29 , serve for removably mounting the second module B on the front panel of the dialysis machine.
The pre-dilution 25 and post-dilution 26 branches each comprise at least a tract of flexible tube which can be obstructed by squeezing. These tracts of flexible tube are positioned in a prefixed position with respect to the post-pump arterial expansion chamber 12 . The correct positioning of the prefixed position is easily reached when mounting the module B on the front panel of the machine, by virtue of the fact that the fluid connection system formed by the second flexible tube 44 and the third flexible tube 45 are positioned stably with respect to the support element of module B, so that the pre-dilution 25 and post-dilution 26 branches (made from the third flexible tube 45 ) are immobile with respect to the support element of module B, although each of them is elastically deformable and therefore closable by squeezing of the valves 52 and 53 .
The branch from the pre-dilution 25 and post-dilution 26 branches which is not fluidly connected to the expansion chamber bearing the replacement fluid pump tube tract 29 can be constrained, directly or via a tract of the extracorporeal blood circuit, to the support element. In the present embodiment, in which the expansion chamber bearing the replacement fluid pump tube tract 29 is the post-pump expansion chamber 12 (which chamber 12 is connected to the pre-dilution branch 25 ), the post-dilution branch 26 can be constrained to the support element via a tract of venous line 7 of the extracorporeal blood circuit. In particular, a tract of venous line 7 is engaged in two recesses afforded in the casing 36 , and the post-dilution branch 26 is fluidly connected to this tract of venous line 7 .
The main branch 24 of the supply line 23 is constrained (for example directly, as in the present embodiment) to the support element. In particular the main branch 24 exhibits at least a support zone that interacts (in a gripping and/or direct contact coupling) with the support element in a tract to that is downstream of the ultrafilter 28 . In more detail, a tract of the main branch 24 arranged downstream of the ultrafilter 28 is engaged (by, for example, a removable joint) in a seating afforded on one of the extensions 35 . This tract of the main branch 24 (which in the present embodiment is part of the second flexible tube 44 ) exhibits, at the ends thereof, two annular projections which are axially distanced from one another and which are arranged externally of the opposite ends of the seating 46 , functioning as stable centring and positioning tabs of the tract of main branch 24 in the seating 46 .
The ultrafilter 28 is supportedly constrained to the support element of module B, in particular to the casing 36 .
The support element can realise at least a mechanical and not fluid interconnection between the expansion chamber bearing the replacement fluid pump tube tract 29 (i.e. the chamber 12 ) and the replacement fluid supply line 23 and/or between the expansion chamber bearing the replacement fluid pump tube tract 29 (chamber 12 ) and the extracorporeal blood circuit. A mechanical and not fluid interconnection can also be operating between the expansion chamber 12 and the venous line 7 (or the post-dilution branch 26 or, respectively, the arterial line 6 (or the pre-dilution branch 25 ).
One of these mechanical and not fluid interconnections comprises, in the present embodiment, one of the extensions 35 in the form of an arm that emerges (on the opposite side with respect to the replacement fluid pump tube tract 29 ) from the expansion chamber 12 which bears the replacement fluid pump tube tract. As already mentioned, this arm exhibits at an end thereof an attachment point (seating 46 ) for the main branch 24 of the supply line 23 . As already mentioned, the support element realises both the mechanical and not fluid interconnection between the chamber 12 and the line 23 , and the mechanical and not fluid interconnection between the chamber 12 and the blood circuit.
The support element of the second module B comprises, in the present embodiment, two elements which are assembled one to the other, i.e. the extensions 35 (integrated with the chamber 12 ) and the protection casing 36 . However it would be possible, in further embodiments of the invention, to have the support element made in an integrated single piece or an assembly of three or more distinct elements.
The second module B comprises an integrated element which defines the expansion chamber supporting the replacement fluid pump tube is tract 29 , i.e. the chamber 12 . This integrated element also defines a part of the support element of the second module B, in particular the extensions 35 .
The integrated element further defines a first conduit 39 for blood inlet into the expansion chamber 12 , a second conduit 50 for replacement fluid inlet, and a third conduit 40 for blood outlet (or blood mixed with replacement fluid) from the expansion chamber 12 .
The first and third blood conduit 39 and 40 belong to the extracorporeal blood circuit and are located on two opposite sides of the above-described expansion chamber 12 and extend in length in a vertical direction, with reference to an operative configuration in which the pump tube tract 29 is coupled to the replacement fluid circulation pump 30 .
The first and third blood conduits 39 , 40 also each have a bottom end which is fluidly connected to an expansion reservoir 47 of the post-pump arterial expansion chamber 12 , and an upper end which is fluidly connected (via the ports 20 and 22 ) to the rest of the arterial line 6 , respectively before and after the post-pump arterial expansion chamber 12 . In particular the first inlet conduit 39 is connected to an initial part of the arterial blood line 6 having the patient end 9 destined for connection with the arterial vascular access; the third outlet conduit 40 is connected to a final part of the arterial blood line 6 having the device end 13 destined for connection to the hemo(dia)filter 5 .
With reference to figures from 7 to 14 , the integrated element defining the chamber 12 is described in greater detail. The chamber 12 comprises the expansion reservoir 47 which is provided with a bottom, a top, at least a first side extending between the bottom and the top, a first access 48 arranged on the first side at a distance from the bottom and top, and a second access 49 .
The first conduit 39 terminates in the first access 48 . A second conduit 50 terminates in the first conduit 39 or, as in the present embodiment, in the expansion reservoir 47 . The first conduit 39 and the second conduit 50 terminate in the first access 48 with, respectively, a first flow direction and a is second flow direction which are incident to one another.
The first conduit 39 terminates in the first access 48 with a first flow direction having at least a motion component directed towards the bottom. The first flow direction has at least a motion component directed towards a second side of the expansion reservoir 47 ; the second side extends between the bottom and top and is opposite the first side.
The second conduit 50 terminates in the expansion reservoir 47 with a second flow direction having at least a motion component directed towards the second side of the expansion reservoir 47 . The second flow direction has at least a motion component directed towards the top. The second flow direction has at least a first motion component that is horizontal and directed towards the inside of the expansion reservoir 47 .
The second conduit 50 comprises an intermediate tract 59 having a flow direction provided with at least a second horizontal motion component going in an opposite direction to the first horizontal motion component. The flow direction of the intermediate tract 59 is provided with at least a vertical motion component.
The first conduit 39 has a diverging tract 51 with a fluid passage that broadens in the direction of the first access 48 . The diverging tract 51 broadens towards the bottom of the reservoir 47 . The expansion reservoir 47 extends prevalently on a lie plane; the diverging tract 51 enlarges prevalently in a perpendicular direction to the lie plane. The diverging tract 51 terminates at the first access 48 .
The first access 48 is elongate and extends in a perpendicular direction to the first side of the reservoir 47 .
The second access 49 is arranged on the bottom of the reservoir 47 . The third conduit 40 terminates in the second access 49 . The third conduit 40 extends in length by the side of the second side of the expansion reservoir 47 .
The first conduit 39 terminates in the first access 48 with a first flow direction directed towards the second access 49 . The first flow direction has at least a motion component which is direction towards the bottom.
The second conduit 50 terminates on the first side of the expansion reservoir 47 below the end of the first conduit 39 . The second conduit 50 terminates either in the first access 48 contiguously below the end of the first conduit 39 (as in the present embodiment), or, in a further embodiment, not illustrated, it terminates in an intermediate access arranged between the first access 48 and the bottom of the reservoir 47 .
The expansion reservoir 47 has an upper part, comprised between the first access 48 and the top, having a greater width than a lower part comprised between the bottom and the first access 48 .
The first conduit 39 meets the second conduit 50 in a connecting zone, and joins the connecting zone in a position above the second conduit 50 .
The first conduit 39 extends lengthwise by the side of the first side of the reservoir 47 . The first conduit 39 is designed to introduce the transported flow (in the present embodiment the arterial blood) into the connecting zone with at least one motion component directed in a downwards direction. The second conduit 50 is designed to introduce the transported flow (in this case the replacement fluid) into the connecting zone with at least a motion component directed upwards. The first conduit 39 and the second conduit 50 are designed so that each of the respective transported flows is introduced into the connecting zone with at least a horizontal motion component directed internally of the expansion reservoir 47 .
The first conduit 39 and the second conduit 50 are arranged on a same side (the first side) of the expansion reservoir 47 . The first conduit 39 is situated above the second conduit 50 .
The first side of the expansion reservoir 47 has an upper zone with a vertical inclination, and a lower zone with an oblique inclination. The oblique lower zone of the first side is inclined in a direction nearing the second side. This oblique inclination determines a narrowing of the expansion reservoir 47 . The zone of the second side that is facing the oblique zone of the first side is substantially vertically oriented. The first conduit 39 has an upper tract having a substantially vertical longitudinal axis, and a lower tract having an oblique longitudinal axis. The oblique axis is inclined in a direction nearing the second side of the expansion reservoir 47 . The first conduit 39 terminates in the expansion reservoir 47 with an oblique inclination.
The first conduit 39 is made in a single piece with the expansion reservoir 47 . The second conduit 50 is made in a single piece with the expansion reservoir 47 . The third conduit 40 is made in a single piece with the expansion reservoir 47 . The chamber 12 is realised by assembly of two half-shells. The two half-shells are obtained by press-forming of a plastic material.
The extracorporeal blood line which includes the chamber 12 is, in the present embodiment, the arterial line 6 . The chamber 12 can, however, be associated (alternatively or in addition to the arterial line 6 ) to the venous line 7 . The chamber 12 in this case would be a mixing chamber for replacement fluid (in post-dilution) for degassing and for monitoring pressure, arranged downstream of the hemo(dia)filter; the inlet port 20 would be connected to the hemo(dia) filter 5 , while the outlet port 22 would be connected to the vascular access.
During treatment, in which the arterial line 6 and the venous line 7 are connected to the patient, the blood pump 8 is activated, so that the blood is removed from the patient via the arterial line 6 , is sent to the hemo(dia)filter 5 , and is returned to the patient via the venous line 7 . The replacement fluid pump 30 is also activated, so that the dialysis fluid is removed from the on-line port 4 of the machine, is made to pass first through the pump tube tract 29 and then the ultrafilter 28 , and is then sent selectively to the chamber 12 on the arterial line 6 (opening the pre-dilution valve 52 operating on the branch 25 and closing the post-dilution valve 53 operating on the branch 26 ) or to the venous line 7 (valve 52 closed and valve 53 open), or to both (valves 52 and 53 both open).
In a case of pre-dilution, the replacement fluid flow enters the expansion reservoir 47 from below, transversally encountering the blood flow that enters the reservoir from above. Both flows are obliquely directed, each with an inlet component into the expansion reservoir 47 which is horizontally directed (with reference to the work position of the chamber 12 ) towards the second side of the expansion reservoir 47 , and a vertical component having an opposite direction to the direction of the flow. The meeting of the two flows causes an effective remixing between the blood and the replacement fluid, so that the mixed liquid (blood and replacement fluid) that exits through the third conduit 40 is homogeneously mixed.
The special conformation and arrangement of the chamber 12 enables both an effective remixing of the blood and replacement fluid and an effective degassing of the liquids entering the expansion reservoir 47 , especially the replacement fluid, thus preventing any air bubbles exiting through the third conduit 40 .
In the absence of pre-dilution (valve 52 closed), the replacement fluid does not reach the chamber 12 , while the blood enters through the first conduit 39 and exits through the third conduit 40 ; since the first conduit 39 terminates directly facing the inlet of the third conduit 40 , the turbulence created is relatively low, reducing to a minimum the formation of foam and flow resistors, while at the same time enabling separation of the air which may still be present in the blood.
Before the treatment is performed the circuit is primed by connecting the patient venous end 16 to the connector 31 and the patient arterial end 9 to a discharge (for example a collection bag or a discharge connected to the exhausted fluid circuit of the dialysis machine). Then the clamp 32 is opened, the valves 52 and 53 are closed, the pump 8 is activated (with the tract 29 not coupled to the pump 30 ) in order to aspirate fluid from the port 4 and to circulate the fluid along the venous line 7 , the blood filter of the hemodiafilter 5 , and the arterial line 6 up to the end 9 . The priming of the post-dilution branch 26 is performed by activating the pump 8 , closing the venous clamp 18 and opening the valve 53 (with the valve 52 closed), while the priming of the pre-dilution branch 25 is done by opening the valve 52 (with the venous clamp 18 and the valve 53 closed).
In a further embodiment (not shown) the support element comprises a selector configured to selectively squeeze the flexible tube tracts of the pre-dilution and post-dilution branches. The selector comprises a movable (e.g. rotatable) member mounted on (e.g. rotatably coupled to) the support element. The movable member includes a first end and a second end and can assume at least two configurations. In a first configuration the first end squeezes one of the flexible tube tracts and in a second configuration the second end squeezes the other of the flexible tube tracts.
LEGEND
1 . Hemo(dia)filtration apparatus
2 . Fresh dialyser fluid port
3 . Exhausted fluid port
4 . On-line port
5 . Hemo(dia)filter
6 . Arterial line
7 . Venous line
8 . Blood pump
9 . Patient arterial end
10 . Pre-pump arterial expansion chamber
11 . Blood pump tube tract
12 . Post-pump arterial expansion chamber
13 . Arterial device end
14 . Venous device end
15 . Venous expansion chamber
16 . Venous patient end
17 . Arterial clamp
18 . Venous clamp
19 . Tubular extensions connected to the chamber 10 for attachment of the blood pump tube tract 11
20 . Blood inlet port of the post-pump arterial expansion chamber
21 . Replacement fluid inlet port of the post-pump arterial expansion chamber 12
22 . Outlet port for blood(-replacement fluid) from post-pump arterial expansion chamber 12
23 . Replacement fluid supply line
24 . Main branch of line 23
25 . Pre-dilution branch of line 23
26 . Post-dilution branch of line 23
27 . Inlet end of line 23
28 . Ultrafilter of replacement fluid
29 . Replacement fluid pump tube tract
30 . Replacement fluid pump
31 . Auxiliary connection of line 23 (for priming)
32 . Auxiliary connection 31 intercept clamp
33 . Intermediate tract of arterial line between the two modules of the hemodiafiltration apparatus
34 . Intermediate tract of venous line between the two modules of the hemodiafiltration apparatus
35 . Support extensions emerging from the post-pump arterial expansion chamber
36 . Casing
37 . Mounting extension
38 . Tubular extensions for supporting the replacement fluid tube tract
39 . First conduit for blood inlet into the post-pump arterial expansion chamber
40 . Third blood outlet conduit of the post-pump arterial expansion chamber
41 . First flexible tube
42 . First tubular connection
43 . Second tubular connection
44 . Second flexible tube
45 . Third flexible tube
46 . Seating predisposed on the support element for fixing the main branch 24
47 . Expansion reservoir
48 . First access of reservoir 47
49 . Second access of reservoir 47
50 . Second inlet conduit of replacement fluid into the post-pump arterial expansion chamber
51 . Diverging tract of the first conduit 39
52 . Pre-dilution control valve
53 . Post-dilution control valve
54 . Connection for service line located at top of expansion reservoir 47
55 . Connection for an ultrafilter vent line
56 . Connection for the auxiliary line provided with the auxiliary connector 31
57 . Connection for an end of the initial tract of replacement fluid line 23 having the inlet 27 at the opposite end
58 . Device for detecting pressure in the blood chamber 12
59 . Intermediate tract of second conduit 50
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An extracorporeal blood chamber ( 12 ) comprises an expansion reservoir ( 47 ) having a first access ( 48 ) arranged laterally and a second access ( 49 ) arranged on the bottom of the chamber ( 12 ). The chamber comprises, integrally with the reservoir, a first conduit terminating in the first access, a second conduit terminating in the first access, and a third conduit terminating in the second access. The extracorporeal blood enters the reservoir through the first conduit and there mixes with an infusion fluid which enters through the second conduit. The resulting mixture exits through the third conduit. The chamber is used in a hemo(dia)filtration apparatus to mix the blood optimally with the replacement fluid.
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CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the priority of U.S. Provisional Application Ser. No. 61/456,435 entitled “Suspension for a tracked climbing machine” filed on Nov. 8, 2010, the entire contents and substance of which are hereby incorporated in total by reference
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not Applicable
DESCRIPTION OF ATTACHED APPENDIX
Not Applicable
BACKGROUND OF THE INVENTION
This invention applies to a category of self-propelled, climbing, mobile platforms that make use of endless tracks to connect to the climbing surface. For this purpose, the term climbing mobile platform refers to a vehicle that is capable of traversing a surface horizontally or vertically in some inclined position relative to the earth horizon. Further, it is intended that the mobile platforms are able to accommodate irregularity in the climbing surface including convex or concave regions. Such platforms may be used to conduct remote operations such as inspection, maintenance, or manufacturing in environments that pose difficulty or danger for human operation. These systems could be used in a wide variety of applications including power production, civil structures, or shipbuilding. A variety of climbing mobile platforms have been proposed to operate in these conditions.
The methods of achieving mobility for climbing platforms include but are not limited to legged locomotion, wheeled devices or endless tracks. The use of endless tracks in climbing platforms provides several advantages, including the potential for a large area of contact between the climbing surface and climbing vehicle. The large area of contact allows for a large distribution of adhering elements such as magnets, suction cups, adhesive, or other device. The endless track-type climbing vehicles presented in previous technologies make use of an endless track that makes contact with the climbing surface over a portion of the track, called here the contact portion of the track. The endless track contains the specific property that it has very high stiffness along the longitudinal axis of the track, but negligible stiffness in all transverse directions and negligible stiffness in bending or torsion. This creates a technical disadvantage in that the endless track is only able to transmit any significant level of forces in a direction along the longitudinal axis of the track. This property also allows the endless track to easily deflect in transverse directions or bend to accommodate irregular climbing surfaces. The result of this high longitudinal stiffness and negligible transverse or bending stiffness is that the endless track is only able to transfer forces normal to the climbing surface at the end portions of the contact region. These forces generally consist of those required to keep the climbing platform in equilibrium and in contact with the climbing surface. Thus, the adhering elements located at each end of the contact region support the majority of the climbing forces.
The performance of an endless-track type climbing platform depends on the ability to transfer forces from the collection of adhering members attached to the track, through the endless track to the platform body. There are a number of technologies that address how these forces are transferred from the endless track to the climbing platform body, and to a smaller degree how these forces are distributed to the collection of adhering members. The mechanism for doing this will be called the suspension system. The invention of this patent provides a novel means to distribute the climbing forces in an optimal manner over all adhering track elements while applying a positive surface normal force on the leading adhering member to ensure that it makes contact with surface when climbing.
The prior art considering tracked climbing vehicles with attached adhering members shows either systems without a suspension, or those with a suspension system designed for secondary purposes (for example, track removal from the climbing surface) rather than to distribute loads among the adhering members. Examples of the related prior art are provided as follows.
U.S. Pat. Nos. 5,435,405, 5,884,642, and Shen and Shen, 2005 show climbing vehicles with adhering members attached to an endless track without a suspension or no consideration given to the suspension. This causes the climbing forces to be transferred to the adhering members through the track and thus concentrates the climbing forces on the adhering members located at the ends of the contract region of the endless track.
U.S. Pat. Nos. 5,894,901 and 4,789,037 show climbing vehicles with adhering members attached to an endless track with press devices to push certain regions of the track into the climbing surface, in particular the leading edge of the track when traveling vertically up. However, these devices do not allow for the vehicle to pull on interior portions of the track in the direction of the surface normal and thus cannot distribute the climbing forces over the endless track.
U.S. Pat. No. 4,828,059 shows a climbing vehicle with adhering members attached to an endless track with a track guide that is used to engage and disengage the adhering members from the climbing surface. During operation, the track guide is not engaged and thus behaves as an endless track system that transfers climbing forces to the adhering members through the track.
U.S. Pat. No. 5,487,440 shows a climbing vehicle with adhering members attached to an endless track with a track guide rigidly attached to the vehicle chassis. This both limits the ability of the endless track to conform to the climbing surface and localizes the climbing loads to a small number of adhering members when traveling over any type of surface irregularity.
Xu and Ma (2002) shows an endless-track type climbing vehicle with type of climbing vehicle with magnets called magnetic suckers. A load distribution mechanism is presented as a three link member connected to the vehicle body with a single spring. The article does not show how the endless track would connect with the load scatter mechanism or how forces are transferred from the track to the mechanism. Further, as presented, the load scatter mechanism localizes moment-balance forces to the leading portion of the load scatter mechanism and similarly the leading edge of the endless track.
This patent most closely relates to a 2010 patent application by Canfield and Beard which demonstrates a climbing platform with endless tracks, adhering members attached directly to the endless tracks, with a compliant beam suspension system that connects the endless tracks to the platform chassis. The compliant beam mechanism allows the suspension to simultaneously adapt to irregularities in the climbing surface, while a collection of springs attached to the compliant beam provide the means to distribute forces among all the adhering members. This invention is unique in that it both distributes surface-normal climbing forces among all the adhering members and provides a force on the adhering member at the end of the contact region to ensure that the adhering member makes contact with the climbing surface.
This patent differs from the 2010 patent application by Canfield and Beard in two significant ways. First, the compliant beam portion of the compliant beam suspension apparatus must provide low rotational stiffness and large rotational deflection about the axis transverse to the axis of the endless track and lying in a plane tangent to the climbing surface at each point along the beam and high rotational stiffness in other directions. For most readily available engineering materials, the elastic modulus permits strains of approximately 2% before plastic deformation occurs. In some special cases, this allowable strain rate may be as high as 6% (for example nickel-titanium type alloys called super-elastic materials). When considering a climbing surface, irregularities in the surface can be defined by the radius of curvature. In order to accommodate large variations in the climbing wall, the suspension must match the curvature of the surface irregularities. This induces strain in the compliant beam suspension proportional to the curvature, and will exceed allowable strain levels for any typical climbing terrain. The second limitation is that lateral forces along the axis transverse to the axis of the endless track and lying in a plane tangent to the climbing surface at each point along the beam are large, and must be transferred through the compliant beam to the platform chassis at the endpoints.
BRIEF SUMMARY OF THE INVENTION
The invention disclosed in this patent provides a novel means to distribute the climbing forces in an optimal manner over all adhering track elements and transfer these to the climbing platform, while applying a positive surface normal force on the leading adhering member to ensure that it makes contact with surface when climbing. Further, it does this without inducing any strain the suspension members that guide the endless track, and it supports lateral along the length of the endless track. It does this through the following manner:
1) The invention offers a suspension that is able to match a large range of surface irregularities without inducing strain in the primary suspension member. It does this by creating the primary suspension member, called the track link guide member, as a serial chain of links connected by revolutes that can independently flex without strain. The invention maintains a slidable connection with the endless tracks along the contact portion by designing all adjoining links to be conjugate, to maintain a solid, uniform slot along the slidable connection. Further, the invention allows for the track link guide member to change length to accommodate changing surface curvature while maintaining fixed contact points with the vehicle chassis through one or more prismatic connections in the links. 2) The invention also shows a suspension with a series of lateral force dyads that transmit lateral forces directly from the track to the climbing platform along the length of the track. These lateral force dyads transmit force while accommodating displacement of the suspension. 3) The invention prescribes the surface-normal load distribution on all the adhering members through a series of springs integrated into the lateral force dyads.
The proposed invention provides the primary features of the 2010 Canfield and Beard patent application—it provides a means to uniformly distribute the normal-surface forces among the adhering members, while solving the two primary limitations of the 2010 Canfield and Beard patent application.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 shows an isometric view of the climbing platform.
FIG. 2 shows an end view of the mobile climbing platform.
FIG. 3 shows a single endless track unit of the mobile climbing platform.
FIG. 4 shows an endless track unit with the interior portions exposed.
FIG. 5 shows the multi-link suspension apparatus.
FIG. 6 shows the track link guide member.
FIG. 7 shows an isometric view of the connection between the track link guide member and endless track.
FIG. 8 shows a cross-sectional view of the connection between the track link guide member and endless track.
FIG. 9 shows a lateral force dyad.
FIG. 10 shows the force distribution member.
FIG. 11 shows the track tensioning system.
FIG. 12 shows a climbing surface with defined directions.
Throughout the figures identical reference numerals denote identical components.
DETAILED DESCRIPTION OF THE INVENTION
Detailed descriptions of the preferred embodiment are provided herein. It is to be understood, however, that the present invention may be embodied in various forms. Therefore, specific details disclosed herein are not to be interpreted as limiting, but rather as a basis for the claims and as a representative basis for teaching one skilled in the art to employ the present invention in virtually any appropriately detailed system, structure or manner.
The invention disclosed here is a multi-link suspension apparatus that is designed to function as an integral part of climbing machine making use of an endless track. The multi-link suspension apparatus is slidably connected to the endless track and prescribes specific stiffness (or compliance) in five spatial directions between the climbing surface and the climbing machine body. These include all cardinal directions in three-dimensional space except the direction of the axis of the endless track.
Stiffness (or contrarily, compliance) in the multi-link and spring suspension apparatus is prescribed through a combination of track link guide member, lateral force dyads, force distribution mechanism and endless track tensioning system.
In operation, the climbing vehicle body is subject to a variety of forces, including gravitational and dynamic loads associated with the vehicle and payload motion, as well as forces generated by the operation of the tooling or equipment attached to the vehicle. To remain in equilibrium (static and dynamic) with the climbing surface, these forces are to be transferred to the climbing surface through the endless track and adhering track members.
The mechanism of this invention prescribes how these forces are transmitted from the vehicle body to the adhering track members over a wide range of surface irregularity or contours. The forces are prescribed through the compliance of the force distribution mechanism and stiffness in the primary track links member and lateral force dyads.
The invention prescribes the stiffness between the climbing platform chassis and endless track in five directions as shown in FIG. 10 ; S 1 ) linear stiffness normal to the climbing surface, S 2 ) linear stiffness in the plane of the climbing surface and normal to the axis of the endless track, S 3 ) rotational stiffness about an axis normal to the climbing surface, S 4 ) rotational stiffness about an axis in the plane of the climbing surface and normal to the axis of the endless track and S 5 ) rotational stiffness about the axis of the endless track.
The stiffness in direction S 1 is prescribed along the entire track to uniformly distribute the forces on the adhering track members. The stiffness in direction S 2 is prescribed to limit transverse deflection of the endless track (high stiffness) The stiffness in direction S 3 is prescribed to limit rotation of the endless track (high stiffness) about an axis normal to the climbing surface. The stiffness in direction S 4 is prescribed to allow low stiffness along the center portion of the endless track to accommodate contours or irregularities in the climbing surface, and high stiffness where the endless track engages the track sprockets. The stiffness in direction S 5 is prescribed to allow low stiffness along the center portion of the endless track to accommodate contours or irregularities in the climbing surface, and high stiffness where the endless track engages the track sprockets.
This invention that achieves the prescribed stiffness consists of four primary components: track link guide member, lateral force dyads, force distributing mechanism and endless track tension adjusting device. The first part is the track link guide member. The track link guide member is slidably connected to the endless track in the contact region. The track link guide member consists of a collection of central links connected serially with a revolute joint and two end links. One end of each central link is concave and the other end convex. At each revolute joint where two links are connected, the convex portion moves inside the concave portion in a conjugate fashion. One or more portions of the track link guide member contains primatics to allow a change in length. At each end of the track link guide member, the track link guide member is connected to the chassis through a revolute joint. The slidable portion of both end links are located tangent to a circle centered at the sprocket pivot, the diameter of this circle is equal to the pitch diameter of the corresponding sprockets. The length of the central links is generally selected to equal 1-2 times the pitch of the endless track members (1-2 times the distance between each endless track member). The serial chain possesses (n+1) degrees of freedom where n is the number of central links in the track link guide member. Note that all revolutes in the track link guide member lie along an axis transverse to the axis of the endless track and parallel to the plane of the climbing surface along the endless track. The track link guide member provides a continuous connection to the endless track along the contact region and allows for large deflection of endless track to adapt to the climbing surface. Note also that the track link guide member could connect to the vehicle chassis through a force distributing mechanism.
The second part of the multi-link suspension apparatus consists of a collection of lateral-force dyads which can be made of two-link pairs, prismatic pairs, or other members. Here, the two-link pair is discussed. One end of each lateral-force dyad is connected to the climbing platform with a revolute. The other end of the lateral-force dyad is connected to the track link guide member through a revolute. All revolutes on the lateral-force dyad are parallel to the revolutes in the track link guide member. The collection of lateral-force dyads serve to provide support to the track link guide member to resist transverse forces on the endless track along the contact region. Thus, the lateral-force dyads resist transverse forces that arise when the climbing platform is turning.
The third component is a force distribution element consisting of a series of springs actuators, or other device that can permit displacement while controlling force, springs will be discussed here. These force distribution elements generally run in parallel with the dyad links. These force distribution springs may be extension, compression, torsional or other type. These force distribution springs connect the climbing platform chassis to the primary track links member to provide a specified stiffness in a direction normal to the climbing surface. The stiffness of each spring is selected to distribute the climbing forces uniformly among the adhering elements.
The fourth component of the multi-link suspension apparatus consists of a tensioning system to maintain a constant tension in the endless track while the system deflects to accommodate irregularities in the climbing surface.
FIGS. ( 1 ) and ( 2 ) show a mobile climbing platform 1 consisting of two track units ( 2 ) and a connecting chassis ( 3 ). The chassis connects two or more track units in either a rigid fashion, or can allow some range of relative motion between two or more track units to allow the track units to better adapt to the climbing surface geometry. The track units are geometrically similar and symmetric; one is shown in FIG. 3 . The track unit consists of an endless track ( 100 ) with an exterior side and interior side with a collection of permanent magnet feet ( 300 ) or other adhering members attached to the exterior side of the endless track. The endless track ( 100 ) passes around a drive sprocket ( 104 ) and track sprocket 106 and passes through the multi-link suspension system ( 110 ). A drive unit ( 108 ) for the track unit can be located internally or externally to the track unit ( 2 ) and can include drive motor, transmission, encoder and brake.
FIG. 4 shows the internal components in the track unit. The drive sprocket ( 104 ) is pivotally attached to the track frame and connected to the transmission output sprocket ( 106 ) through chain ( 108 ). The endless track tensioning mechanism consists of an arm ( 142 ) pivotally connected to the track frame and an idler sprocket ( 144 ) pivotally attached to the tensioning arm ( 142 ). The track sprocket ( 110 ) is pivotally attached to the track frame. The endless track ( 100 ) engages the drive sprocket, track sprocket and tensioning sprocket. The multi-link and spring suspension apparatus ( 200 ) is pivotally attached to the drive sprocket ( 104 ) by revolute joint ( 115 ) and the track sprocket ( 110 ) by revolute joint ( 116 ) and to the track unit frame at revolute joints ( 130 ), ( 131 ), ( 132 ).
FIG. 5 shows the multi-link suspension apparatus ( 200 ) isolated from the track unit. The multi-link suspension apparatus consists of a track link guide member ( 210 ), one or more lateral force dyads ( 230 ) and one or more force distribution elements ( 240 ). FIG. 5 shows four lateral force dyads ( 230 ) and four force distribution elements ( 240 ). The track link guide member ( 210 ) guides the endless track along a slidable connection through a slot in the track link guide member ( 211 ). The links of the track link guide member are connected to each other through revolute joints ( 212 ) and one or more prismatic joints ( 213 ) and connect to the track unit through revolute joints ( 214 ). The lateral force dyads ( 230 ) are connected to the track link guide member ( 210 ) with a revolute joint ( 231 ) and connect to the track unit through revolute joints ( 232 ). The force distribution elements ( 240 ) transfer loads from the endless track through the track link guide member ( 210 ) to the track unit. Four force distribution elements ( 240 ) are shown on the multi-link suspension apparatus in FIG. 5 as rotational springs that create a torque on the input link ( 233 ) of the lateral force dyad ( 230 ) and thus create a tensile force on the track link guide member. One end of the force distribution element ( 241 ) connects to the track unit while the other end ( 242 ) is connected to the input link ( 233 ) of the lateral force dyad. Note that other methods for the force distribution element could be used including linear springs, pneumatic or electric actuators. The multi-link suspension apparatus serves multiple roles; it allows the track to adhere to uneven track surfaces, it distributes the load in a preferred manner over the individual magnetic elements attached to the endless track, and it allows the mobile climbing robotic welding system to operate in horizontal, vertical and inverted orientations.
The track link guide member is shown isolated in FIG. 6 . The track link guide member is slidably connected to the endless track in the region in which the adhering members of the endless track make contact with the climbing surface or contact region. The track link guide member consists of a collection of track links that are connected through revolute joints in a series chain. The track links can be one of several types; binary central links ( 215 ), ( 216 ), load central links ( 217 ), pivot end link ( 218 ) and sliding end link ( 219 ). The binary central, load central and pivot end links are connected serially with revolute joints at ( 220 ), ( 221 ), ( 222 ) and ( 223 ). The sliding end link is connected to the binary central link through a sliding connection at ( 235 ). Each of the track links consists of an outer side and inner side. The inner side of each track link contains a slot with dimensions appropriate to accept a mating protrusion ( 101 , FIG. 7 ) on the interior side of the endless track. The track link members are connected in a way to maintain a continuous, open slot passing through the track link guide member. The revolute joints that connect the track links are located in such way that adjacent, connected track links share an instant center that passes through the centerline of the slot. The track link members are connected in a way to maintain a smooth transition of the slot passing through the track link guide member, but making each track link member a conjugate pair of its adjacent track link member. As an example of how this is done, one end of each central link is concave and the other end convex. At each revolute joint where two links are connected, the convex portion moves inside the concave portion in a conjugate fashion. One end of the pivot end link ( 218 ) is connected to the drive sprocket axis through a revolute joint ( 224 ). One end of the sliding end link ( 219 ) is attached to the track sprocket axis through a revolute joint. The lateral force dyads connect to the track link guide member at revolute joints ( 232 ). The endless track slot portion of the pivot end link and sliding end link are located tangent to a circle centered at the sprocket pivot, the diameter of this circle is equal to the pitch diameter of the corresponding sprockets. The length of the binary central links and load central links are generally selected to equal 1-2 times the pitch of the endless track members (1-2 times the distance between each endless track member). The serial chain possesses (n+1) degrees of freedom where n is the number of central links in the track link guide member. Note that all revolutes in the primary track links member lie along an axis transverse to the axis of the endless track and parallel to the plane of the climbing surface along the endless track.
FIG. 7 shows more detail of the slidable connection between the track link guide member ( 210 ) and the endless track ( 100 ). The slot in the track link guide member ( 211 ) is matched in dimension to the protrusion ( 101 ) on the endless track. The protrusion ( 101 ) of the endless track can freely slide in one dimension through the slot ( 211 ) along the longitudinal axis of the track link guide member. The slot ( 211 ) can transfer forces to the protrusion ( 101 ) in directions transverse to the longitudinal axis of the track link guide member. The protrusion ( 101 ) on the endless track can consist of a flange as shown or other mating element such as a roller.
FIG. 8 shows a cross-section view of the slidable connection between the track guide member ( 210 ) and the endless track ( 100 ). The slot in the track link guide member ( 211 ) is matched in dimension to the protrusion ( 101 ) on the endless track. The protrusion ( 101 ) of the endless track can freely slide in one dimension through the slot ( 211 ) along the longitudinal axis of the track link guide member. The slot ( 211 ) can transfer forces to the protrusion ( 101 ) in directions transverse to the longitudinal axis of the track link guide member. The protrusion ( 101 ) on the endless track can consist of a flange as shown or other mating element such as a roller.
FIG. 9 shows a lateral force dyad ( 230 ). The lateral force dyad consists of a two link pair, one the input link ( 233 ) and the second a coupler link ( 234 ). The input link ( 233 ) connects to the track unit through a revolute joint ( 231 ). The coupler link connects to the track link guide member through a revolute joint ( 232 ). All revolutes on the lateral-force dyad are parallel to the revolutes in the track link guide member. The links in the lateral force dyad and bearings that form the revolutes are designed to support transverse (out of plane) loads and thus transmit these transverse loads from the track link guide member to the track unit.
The third component is a force distribution element ( 240 ) as shown in FIG. 10 . The force distribution element in general can consist of a series of springs that generally run in parallel with the dyad links. FIG. 8 shows the force distribution element ( 240 ) as a torsion spring that lies on a support spool ( 243 ). One end ( 241 ) of the torsion spring pushes against the track unit while the other end ( 242 ) pushes against the input link ( 233 ) of the lateral force dyad and thus can create tensile forces in the coupler link ( 234 ) and apply tension or compression forces on the track link guide member. The force distribution springs are selected through an optimal synthesis process that has uniform load distribution on the adhering members as its objective function, and uses a mechanics model of the system over representative climbing surfaces to evaluate the objective function over the design parameters. These force distribution springs connect the climbing platform chassis to the track link guide member to provide a specified stiffness in a direction normal to the climbing surface. The stiffness of each spring is selected to distribute the climbing forces uniformly among the adhering elements.
The fourth component of the multi-link and spring suspension apparatus consist of a track tensioning system to maintain a constant tension in the endless track while the system deflects to accommodate irregularities in the climbing surface. FIG. 9 shows the track tensioning system. The endless track tensioning mechanism consists of an arm ( 142 ) pivotally connected to the track frame and an idler sprocket ( 144 ) pivotally attached to the tensioning arm ( 142 ) and is tensioned through a spring ( 146 ).
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An endless-track type climbing vehicle containing a multi-link suspension apparatus to uniformly distribute the forces on the on the adhering members while traversing irregular climbing surfaces. The multi-links suspension apparatus is able to conform to large range of surface irregularities while providing push and pulling forces on the adhering members to uniformly distribute the climbing loads on the adhering members. The result is a climbing machine that can accommodate large surface irregularities while maximizing the climbing payload with a minimum number and size of adhering members.
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BACKGROUND OF THE INVENTION
This is a continuation in part of copending U.S. Ser. No. 168,177 filed Mar. 15, 1988 which is a continuation of U.S. Ser. No. 774,051 filed Sept. 9 1985, the latter of which issued as U.S. Pat. No. 4,752,602 on June 21, 1988. Both of these applications and the patent are incorporated by reference herein.
The present invention concerns certain peptide esters and their uses, for example, in the ablation of certain cell-mediated immune responses. For brevity and clarity, many of the terms used herein have been abbreviated and these abbreviations include those shown in Table 1. Research involved in the development of the invention was supported by grants from the United States government.
L-leucine methyl ester (Leu-OMe) has previously been used as a lysosomotropic agent (Thiele et al. (1983) J. Immunol. V 131, pp 2282-2290; Goldman et al. (1973) J. Biol. Chem. V 254, p 8914). The generally accepted lysosomotropic mechanism involved leu-OMe diffusion into cells and into lysosomes, followed by intralysosomal hydrolysis to leucine and methanol. The more highly ionically charged leucine, largely unable to diffuse out of the lysosome, caused osmotic lysosomal swelling and rupture. The fate of leu-OMe subjected to rat liver lysosomes was additionally suggested by Goldman et al. (1973) to involve a transpeptidation reaction and a resultant species--"presumably the dipeptide" which was "further hydrolyzed to free amino acids". A subsequent and related paper by Goldman (FEBS (Fed. Europ. Biol. Sci.) Letters V 33, pp 208-212 (1973)) affirmed that non-methylated dipeptides were thought to be formed by lysosomes.
L-amino acid methyl esters have been specifically shown to cause rat liver lysosomal amino acid increases (Reeves (1979- J. Biol. Chem. V 254, pp 8914-8921). Leucine methyl ester has been shown to cause rat heart lysosomal swelling and loss of integrity (Reeves et al., (1981) Proc. Nat'l Acad. Sci., V 78, pp 4426-4429).
TABLE 1______________________________________Abbreviations Symbol______________________________________SubstanceL-leucine leu or LL-phenylalanine phe or PL-alanine ala or AlL-glycine gly or GL-serine ser or SL-tyrosine tyr or TL-arginine arg or ArL-lysine lys or LyL-valine val or VL-isoleucine ile or IL-proline pro or PL-glutamic acid glu or GL-aspartic acid asp or AsL amino acid methyl esters e.g. Leu--OMeL amino acid ethyl esters e.g. Leu--OEtL amino acid benzyl esters e.g. Leu--OBzD-amino acids e.g. D-LeuD-amino acids methyl esters e.g. D-Leu--OMedipeptides of L-amino acids e.g. Leu--Leumethyl esters of dipeptide e.g. Leu--Leu--OMeL amino acids or LLOMedipeptide amides e.g. L-Leu--L-Leu--NH.sub.2dipeptidyl peptidase-I DPPIcell fraction or typemononuclear phagocytes MPpolymorphonuclear leucocytes PMNnatural killer cells NKperipheral blood lymphocytes PBLperipheral blood mononuclear cells PBMcytotoxic T-lymphocytes CTLglass or nylon wool adherent cells ACglass or nylon wool non-adherent NACcellsOther Materialsphosphate buffered saline PBSthin layer chromatography TLCfluorescence activated cell sorter FACSmixed lymphocyte culture MLCMiscellaneouseffector:target cell ratio E:Tfetal bovine serum FBSUniversity of Texas Health UTHSCDScience Center, Dallas, Texas.Standard error of mean SEMprobability of significant pdifference (Student's t-test)Graft versus host disease GVHDMaximum velocity VmaxMicromolar micro-MLevel at which there is a LD.sub.5050% loss of cell functionTrichloracetic acid TCAPhenylmethylsulfonyl fluoride PMSFGlycylphenylalanine diazomethane Gly--Phe--CHN.sub.2Mean survival time MST______________________________________
Natural killer cells are large granular lymphocytes that spontaneously lyse tumor cells and virally-infected cells in the absence of any known sensitization. This cytotoxic activity can be modulated by a host of pharmacologic agents that appear to act directly on NK effector cells. NK activity has been shown to be augmented after exposure to interferons (Gidlund et al., Nature V 223, p 259), interleukin 2, (Dempsey, et al. (1982) J. Immunol. V 129, p 1314) (Domzig, et al. (1983) J. Immunol. V 130, p 1970), and interleukin 1 (Dempsey et al.. (1982) J. Immunol. V 129, p 1314), whereas target cell binding is inhibited by cytochalasin B, (Quan, et al. (1982) J. Immunol. V 128, p 1786), dimethyl sulfoxide, 2-mercaptoethanol, and magnesium deficiency (Hiserodt, et al. (1982) J. Immunol. V 129, p 2266). Subsequent steps in the lytic process are inhibited by calcium deficiency (Quan et al. (1982) J. Immunol. V 128, p 1786, Hisercdt, et al. (1982) J. Immunol. V 129, p 2266), lysosomotropic agents (Verhoef, et al. (1983) J. Immunol. V 131, p 125), prostaglandin E2 (PGE 2 (Roder, et al. (1979) J. Immunol. V 123, p 2785, Kendall, et al. (1980) J. Immunol. V 125, p 2770}, cyclic AMP (Roder, et al. (1979) J. Immunol. V 123, p 2785, Katz (1982) J. Immunol. V 129, p 287}, lipomodulin (Hattori, et al. (1983) J. Immunol. V 131, p 662), and by antagonists of lipoxygenase (Seaman (1983) J. Immunol V 131 p 2953). Furthermore, it has been demonstrated that PGE2 and reactive metabolites of oxygen produced by monocytes (MP) or polymorphonuclear leukocytes (PMN) can inhibit NK cell function (Koren, et al. (1982) Mol. Immunol. V 19, p 1341; and Seaman, et al. (1982) J. Clin. Invest. V 69, p 876).
Previous work by the present applicants has examined the effect of L-leucine methyl ester on the structure and function of human peripheral blood mononuclear cells (PBM) (Thiele, et al. (1983) J. Immunol. V 131, p 2282.
Human peripheral blood mononuclear cells (PBM) are capable of mediating a variety of cell-mediated cytotoxic functions. In the absence of any known sensitization, spontaneous lysis of tumor cells and virally-infected cells is mediated by natural killer cells (NK) contained within the large granular lymphocyte fraction of human PBM Timonen et al.. (1981) v. J. Exp Med. V 153 pp 569-582. After lymphokine activation, additional cytotoxic lymphocytes capable of lysing a broad spectrum of tumor cell targets can be generated in in vitro cultures (Seeley et al. (1979) J. Immnunol. V 123, p 1303; and Grimm et al. (1982) J. Exp. Med. V 155, p 1823). Furthermore, lymphokine activated peripheral blood mononuclear phagocytes (MP) are also capable of lysing certain tumor targets (Kleinerman et al. (1984) J. Immunol. V 133, p 4). Following antigen-specific stimulation, cell-mediated lympholysis can be mediated by cytotoxic T lymphocytes (CTL).
While a variety of functional and phenotypic characteristics can be used to distinguish these various types of cytotoxic effector cells, a number of surface antigens and functional characteristics are shared. Thus, the antigens identified by the monoclonal antibodies OKT8 (Ortaldo et al. (1981) J. Immunol. V 127, p 2401; and Perussia et al. (1983) J. Immunol. V 130, p 2133), and OKTll (Perussia et al. (1983) J. Immunol. V 130, p 2133; and Zarling et al. (1981) J. Immunol. V 127, p 2575) are found on both CTL and NK while the antigen identified by OKMl is shared by MP and NK (Zarling et al. (1981) J. Immunol. V 127, p 2575; Ortaldo et al. (1981) J. Immunol. V 127, p 2401; Perussia et al. (1983) J. Immunol. V 130, p 2133; and Breard et al. (1980) J. Immunol. V 124, p 1943. Furthermore, cytolytic activity of both NK and MP is augmented by interferons, (Kleinerman et al. (1984) J. Immunol. V 133, p 4; Gidlund et al. (1978) Nature V 223, p 259; and Trinchieri et al. (1978) J. Exp. Med. V 147, p 1314). Finally, use of metabolic inhibitors has demonstrated some parallels in the lytic mechanism employed by CTL and NK (Quan et al. (1982) J. Immunol. V 128, p 1786; Hiserodt et al. (1982) J. Immunol. V 129, p 1782; Bonavida et al. (1983) Immunol. Rev. V 72, p 119; Podack et al. (1983) Nature V 302, p 442; Dennert et al. (1983) J. Exp. Med. V 157, p 1483; and Burns et al. (1983) Proc. Nat'l. Acad. Sci. V 80, p 7606).
SUMMARY OF THE INVENTION
A peptide, amide or ester consisting essentially of natural or synthetic L-amino acids with hydrophobic side chains may be used to deactivate natural killer cells (NK). Preferable amino acids of such peptides are leucine, phenylalanine, valine, isoleucine, alanine, proline, glycine or aspartic acid beta methyl ester. Preferable dipeptides are L leucyl L-leucine, L-leucyl L-phenylalanine, L-valyl L-phenylalanine, L-leucyl L-isoleucine, L-phenylalanyl L-phenylalanine, L-valyl L-leucine, L-leucyl L-alanine, L-valyl L-valine, L-phenylalanyl L-leucine, L-prolyl L-leucine, L-leucyl L-valine, L-phenylalanyl L-valine, L glycyl L-leucine, L-leucyl L-glycine or L-aspartyl beta methyl ester L-phenylalanine. The most preferable dipeptides are glycyl L-phenylalanine, L-leucyl L-leucine, L-leucyl L-phenylalanine, L-valyl L-phenylalanine, L-phenylalanyl L-leucine, L-leucyl L-isoleucine, L-phenylalanyl L-phenylalanine and L-valyl L-leucine.
The amide or ester of the peptide is preferably a benzyl, methyl ethyl or alkyl of up to about four carbon atoms such as propyl, isopropyl, butyl or isobutyl. Larger alkyl groups may be used. Aralkyl or aryl derivatives, for example benzyl and napthyl may be particularly effective.
The present invention further involves a method for deactivating natural killer cells or cytotoxic T-lymphocytes comprising the step of treating said cells with an aqueous solution comprising a biologically effective level of a dipeptide in ester or substituted amide form consisting essentially of natural or synthetic L-amino acids with hydrophobic side chains, said ester form being an aryl, alkaryl or aralkyl ester and said amide form being a substituted amide. This aqueous solution more preferably comprises a biologically effective level of a dipeptide in ester or substituted amide form, said dipeptide consisting essentially of at least one of L-leucine, L-phenylalanine, L-valine, L-isoleucine, L-alanine, L-proline, glycine, and L-aspartic acid beta methyl ester, said ester form being an aryl, alkaryl or aralkyl ester and said amide form being a substituted amide. The cells being deactivated may be in vitro or may be yet within an animal. In the latter case the animal is parenterally administered a biologically effective amount of the dipeptide in ester or substituted amide form.
This deactivation of natural killer cells and cytotoxic T-lymphocytes may also be adapted as a method for inhibiting bone marrow graft versus host disease comprising the step of contacting the bone marrow cells to be grafted with an aqueous solution comprising a biologically effective level of a dipeptide in ester or substituted amide form consisting essentially of natural or synthetic L-amino acids with hydrophobic side chains, said ester form being an aryl, alkaryl or aralkyl ester and said amide form being a substituted amide. This aqueous solution again more preferably comprises a biologically effective level of a dipeptide in ester or substituted amide form, said dipeptide consisting essentially of at least one of L-leucine, L-phenylalanine, L-valine, L-isoleucine, L-alanine, L-proline, glycine, and L-aspartic acid beta methyl ester, said ester form being an aryl, alkaryl or aralkyl ester and said amide form being a substituted amide. For in vitro deactivation of natural killer cells or cytotoxic T-lymphocytes, the biologically effective level should be between about 1 micromolar and about 250 micromolar, depending upon the particular agent being used and its effectiveness.
Graft vs. host disease (GVHD) remains one of the main problems associated with bone marrow transplantation. The current studies were undertaken to determine whether treatment of the donor inoculum with the anticytotoxic cell compound L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) would alter the development of GVHD in a murine model. Irradiated recipient mice transplanted with a mixture of control bone marrow and spleen cells from naive semiallogeneic donors died rapidly from GVHD, whereas the recipients of cells incubated with 250 micro-M Leu-Leu-OMe all survived. In addition, Leu-Leu-OMe treatment of cells obtained from donors immunized against host alloantigens resulted in significantly prolonged survival. Phenotypic characterization of spleen cells from the various groups of mice that had received Leu-Leu-OMe-treated cells and survived consistently revealed the donor phenotype. Treatment of marrow cells with 250 micro-M Leu-Leu-OMe appeared to have no adverse effects on stem cell function. Erythropoiesis was undiminished, as assayed by splenic 5-iodo-2,-deoxyuridine- 125 I uptake. Moreover, granulocytic and megakaryocytic regeneration were histologically equivalent in the spleens of recipients of control or Leu-Leu-OMe-treated cells. Treatment of the donor inoculum with Leu-Leu-OMe thus prevents GVHD in this murine strain combination with no apparent stem cell toxicity.
In clinical application, the present invention additionally involves a method of inhibiting the rejection of tissue transplanted into a host. This method comprises the steps of identifying a prospective transplant recipient; and treating the prospective recipient with an aqueous solution comprising a biologically effective level of a dipeptide in ester or substituted amide form consisting essentially of natural or synthetic L-amino acids with hydrophobic side chains, said ester form being an aryl, alkaryl or aralkyl ester and said amide form being a substituted amide. This aqueous solution also more preferably comprises a biologically effective level of a dipeptide in ester or substituted amide form, said dipeptide consisting essentially of at least one of L-leucine, L-phenylalanine, L-valine, L-isoleucine, L-alanine, L-proline, glycine, and L-aspartic acid beta methyl ester, said ester form being an aryl, alkaryl or aralkyl ester and said amide form being a substituted amide.
A similar clinical method for treating a patient with aplastic anemia is further a component of the present invention, the method differing primarily in comprising the initial step of identifying a patient with aplastic anemia.
Likewise, the above procedure may be used for treating a patient having a tumor sensitive to treatment with hydrophobic dipeptide esters or amides, this method differing primarily in that it first involves the step of identifying a patient with such a tumor. Such tumors characteristically are cells similar to natural killer cells or cytotoxic T-lymphocytes.
A patient with an autoimmune disease, thought to be mediated by natural killer cells and/or cytotoxic T-lymphocytes may also be treated by the methods of the present invention. The method would initially comprise the step of identifying a patient with autoimmune disease and would thereafter be similar to that described for the other clinical disorders.
For clinical treatments involving parenteral administration of the compounds of the present invention, the biologically effective amount administered is between about 10 mg/kg body weight and 300 mg/kg body weight; preferably about 1×10 -4 moles/kg body weight. The aqueous solutions of the present invention include any of those suitable for in vivo administration free of toxins and preferably being of an approximate physiological pH and osmolality.
Preferred substituted dipeptide amides of the present invention include those having an alkyl, aryl, aralkyl or alkaryl substituent. A preferred substituted amide form has an aryl substituent, most preferably beta napthyl. A particularly preferred specific dipeptide substituted amide usable in the practice of the present invention is glycyl L-phenylalanyl beta napthylamide.
Preferred dipeptide esters of the present invention include those formed with an alkaryl alcohol, most preferably benzyl alcohol. The term "alkaryl" is used herein to indicate an alkyl group bound in amide or ester linkage to the dipeptide and having an aryl group bound thereto. A particularly preferred dipeptide ester of the present invention is L-leucyl-L-leucyl benzyl ester. The term "aralkyl" is used herein to indicate an aryl group bound in amide or ester linkage to a dipeptide of the present invention and having an alkyl group bound thereto. It is understood that those skilled in the art may make many variations in group substitutions on the alkyl, aryl, aralkyl and alkaryl groups substituents of the present invention and still be within the presently claimed invention.
Preferred dipeptides of the present invention include L-leucyl L-leucine, L-leucyl L-phenylalanine, L-valyl L-phenylalanine, L-phenylalanyl L-leucine, L-leucyl L-isoleucine, L-phenylalanyl L-phenylalanine, L-valyl L-leucine, L-leucyl L-alanine, L-valyl L-valine, L-prolyl L-leucine, L-leucyl L-valine, L-phenylalanyl L-valine, glycyl L-leucine, L-leucyl glycine, and L-aspartyl beta methyl ester L-phenylalanine. A more preferred group of dipeptides is L-leucyl L-leucine, L-leucyl L-phenylalanine, L-valyl L-phenylalanine, glycyl L-phenylalanine, L-phenylalanyl L-leucine, L-leucyl L-isoleucine, L-phenylalanyl L-phenylalanine and L-valyl L-leucine.
The present invention describes a general method for deactivating natural killer cells or cytotoxic T-lymphocytes. This general method comprises the step of treating said cells with an aqueous solution comprising a biologically effective level of a compound which competitively inhibits lymphocyte uptake of Leu-Leu-OMe and is polymerized by dipeptidyl peptidase I to form a membranolytic product. This more general method may be applied as a method of inhibiting the rejection of tissue transplanted into a host. In this application the method comprises the steps of identifying a prospective transplant recipient and treating the prospective recipient with a compound which competitively inhibits lymphocyte uptake of Leu-Leu-OMe and is polymerized by dipeptidyl peptidase I to form a membranolytic product.
Patients with aplastic anemia may be likewise treated by initially identifying a patient with aplastic anemia and then treating the patient with a compound which competitively inhibits lymphocyte uptake of Leu-Leu-OMe and is polymerized by dipeptidyl peptidase I to form a membranolytic product.
This more general method may also be used to treat a patient with an autoimmune disease. The method then comprises the steps of identifying a patient with autoimmune disease and then treating the patient with a compound which competitively inhibits lymphocyte uptake of Leu-Leu-OMe and is polymerized by dipeptidyl peptidase I to form a membranolytic product.
The present invention also includes a method for treating a patient having a tumor which is rich in dipeptidyl peptidase I (i.e., at least about 0.3 nM napthylamine/hr/ug protein). The method comprises the steps of identifying a patient with such a tumor, and treating the patient with a compound which competitively inhibits lymphocyte uptake of Leu-Leu-OMe and is polymerized by dipeptidyl peptidase I to form a membranolytic product.
An analogous method for inhibiting bone marrow graft versus host disease may also be so generalized. Such a method comprises the step of contacting bone marrow cells to be grafted with an aqueous solution comprising a biologically effective level of a compound which competitively inhibits lymphocyte uptake of Leu-Leu-OMe and is polymerized by dipeptidyl peptidase I to form a membranolytic product.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows that whereas ablation of NK function during incubation with Leu-OMe can be blocked by lysosomotropic agents, there is a product formed during incubation of Leu-OMe with MP or PMN which has effects on NK function no longer blocked by lysosomal inhibitors.
FIG. 2 shows Leu-OMe products of PMN in terms of radioactivity and NK suppressive effects of TLC fractions.
FIGS. 3A and 3B show the CI mass spectra of TLC fractions with NK toxic activity (FIG. 3A) and of synthetic Leu-Leu-OMe (FIG. 3B).
FIGS. 4A and 4B show the effects of various leucine-containing compounds on losses of NK function from MP-depleted lymphocytes after washing for 2 hours (FIG. 4A, Expt. 1) or 18 hours (FIG. 4B, Expt. 2).
FIG. 5 shows the NK-toxicity of various dipeptide esters.
FIG. 6 shows the loss of NK and MP from PBM incubated with Leu-Leu-OMe at various concentrations.
FIG. 7 shows the toxicity of various Leu-Leu-OMe concentrations for selected cell types.
FIG. 8 shows the Leu-Leu-OMe mediated elimination of precursors of cytotoxic T lymphocytes activated NK (A c NK) and NK.
FIG. 9 shows the sensitivity of activated NK and CTL to treatment with Leu-Leu-OMe.
FIG. 10 shows the time-dependent uptake of Leu-Leu-OMe by PBL.
FIG. 11 shows the concentrations dependence of Leu-Leu-OMe uptake by PBL.
FIG. 12 schematically describes the effects upon RBC lysis by Leu-Leu-OMe in the presence ( ) and absence ( ) of exogenous DPPI.
FIGS. 13A-13H show RBC lysis as dependent upon the presence (+) or absence (-) of DPPI with concentration gradients of Leu-Leu-OMe (FIG. 13A); D-Leu-D-Leu-OMe (FIG. 13B); Leu-Leu-NH 2 (FIG. 13C); Leu-Leu-OBenzyl (FIG. 13D); Ser-Leu-OMe (FIG. 13E); Val-Phe-OMe (FIG. 13F); Leu-Phe-OMe (FIG. 13G); and Leu-Tyr-OMe (FIG. 13H).
FIGS. 14A and 14B show schematic structures of leucyl-(N)Methyl leucine methyl ester (FIG. 14B) and a thiopeptide analog of Leu-Leu-Ome (FIG. 14A).
FIGS. 15A-15C show various examples of dipeptide esters with non-physiological R groups.
FIG. 16 shows the survival of naive B6→B6D2Fl mice. Donor bone marrow and spleen cells were obtained from naive B6 mice and mixed at various ratios prior to incubation and transfer into lethally irradiated B6D2Fl mice. FIGS 16A shows that when 25×10 6 donor cells (spleen to marrow ratio 2.5:1) were transplanted, recipients of untreated cells had a median survival time (MST) of 19 d, recipients of cells treated with 125 micro-M Leu-Leu-OMe had a MST of 41.5d (P<0.001), and recipients of cells treated with 250 micro-M Leu-Leu-OMe all survived >120 d. FIG. 14B shows that when 50×10 6 donor cells (spleen to marrow ratio 5:1) were transplanted, recipients of untreated cells had an MST of 14 d, and recipients of cells treated with 250 micro-M Leu-Leu-OMe all survived >200 d.
FIG. 17 shows the survival of immune B6→B6D2Fl mice. Donor bone marrow and spleen cells were obtained from B6 mice previously immunized against B6D2Fl alloantigens, incubated in the presence or absence of B6D2Fl mice. When 37×10 6 donor cells (spleen to marrow ratio 3.7:1) were transplanted, recipients of untreated cells died with an MST of 11 d and recipients of cells treated with 250 micro-M Leu-Leu-OMe had a MST of 49 d (P<0.001). Three of nine of the mice receiving Leu-Leu-OMe treated cells survived >90 d.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The present invention concerns new compounds and their uses in ablating particular cell types and their functions. The presently described invention relates to the discovery that peptide esters and amides may be cytotoxic to particular cell types.
It has further been found that alkyl aralkyl and aryl esters or amides of peptides consisting essentially of natural or synthetic amino acids with hydrophobic side chains may function cytotoxically to deactivate natural killer cells (NK) and cytotoxic T lymphocytes (CTL). By the term "hydrophobic" as used herein, is meant uncharged in aqueous solution at physiological pH and also as having no hydroxyl, carboxyl or primary amino groups.
Treatment of NK or CTL with an effective level of a peptide amide or ester consisting essentially of natural or synthetic amino acids with hydrophobic side chains serves to deactivate the cytotoxic functions of said cells. An effective level varies from circumstance to circumstance but generally lies between about 25 micromolar and about 250 micromolar. An effective level for a whole animal dose generally lies between about 100 mg/kg and about 300 mg/kg.
Both methyl ethyl and benzyl esters or amides of peptides consisting essentially of natural or synthetic amino acids having hydrophobic side chains have been specifically found to deactivate natural killer cells (NK) or cytotoxic T lymphocytes (CTL) and other alkyl esters of these peptides are confidently predicted to have similar or superior effects.
Deactivation of NK or CTL cells with such peptide esters or amides should increase the success of allogeneic bone marrow transplants by lowering the incidence of graft-versus-host disease (GVHD) and thus lessening the incidence of transplant rejection.
Graft versus host disease (GVHD) is a major problem in allogeneic bone marrow transplantation. It occurs in approximately 70% of transplant recipients and causes death in 20% of those (Wells, et al. p 493 in Basic and Clinical Immunology. Fundenbergo et al. (editors) 2nd ed. Lange, (1978)). The disease occurs when cells of the graft (donor) attack the host tissue, causing abnormalities in the immune system and gastrointestinal tract, as well as skin rashes and liver dysfunction. Although T lymphocytes have traditionally been considered to be the primary effector cells in GVHD, recent studies have shown a correlation between the occurrence of the disease and the appearance of NK activity soon after transplantation. These results implicate the donor's NK cells in the etiology of GVHD. Moreover, other studies demonstrate that high levels of NK activity in a bone marrow recipient prior to transplantation are associated with GVHD (Dokhelar et al. (198I) Transplantation V 3I p 61; Lopez et al. (1979) Lancet V 2 p I103; and Lopez et al. (1980) Lancet V 2 p 1025). Thus, it is theorized that both host and donor NK cells contribute to the development of the disease.
Current regimens for the prevention and treatment of GVHD consist of depleting T-lymphocytes from the donor marrow prior to transplantation and giving the recipient immunosuppressive drugs such as cyclophosphamide and methotrexate, both before and after transplantation. The effectiveness of these regimens might be enhanced by treating donor bone marrow and transplant recipients with dipeptide methyl esters. Potential problems with these procedures include possible non-specific toxicity of therapeutic dipeptide alkyl esters and the re-emergence of NK activity from precursors not sensitive to therapeutic dipeptide alkyl esters.
Currently, bone marrow transplantation is used as a major mode of therapy in treating aplastic anemia, acute myelogenous leukemia and a variety of immunodeficiency states. As mentioned above, a major complication of this therapy is graft-versus-host disease (Sullivan et al., Blood V 57, p 207). Severity of GVHD in man correlates with pretransplant levels of natural killer (NK) activity (Lopez et al., Lancet V 2, p 2101). Thus, by virtue of its ability to diminish NK function in vivo, it is contemplated that Leu-Leu-OBz administration, for example, to bone marrow samples prior to their transplantation will be efficacious in diminishing this complication. An effective level of the peptide esters or amides of the present invention for in vitro deactivation of natural killer cells is between about 10 micromolar and about 250 micromolar.
Furthermore, in both murine and human models, the incidence of GVHD is decreased by in vitro treatment of donor bone marrow with agents that deplete mature T cells (Korngold et al., Exp. Med. V 148, p 168v; Reisner et al., Blood V 61, p 341). Since cytotoxic T cells (CTL) derived from donor bone marrow appear to be the final mediators of GVHD, in vitro treatments of donor bone marrow with an agent which selectively damages cytotoxic T cell precursors is also likely to be of benefit. Since such an in vitro action of amides and esters of the present invention, for example Leu-Leu-OMe has now been demonstrated it was expected that these agents would be of benefit in pre-treating donor bone marrow. An effective level of the esters or amides of the present invention for treatment of bone marrow to be transplanted should be between about 10 micromolar and 250 micromolar for ablation of GVHD-mediating CTL and NK. This prediction of effective GVHD prevention has been further supported by experiments described herein.
A second problem in bone marrow transplantation is the failure of engraftment (the transplant does not "take" or is rejected). This problem occurs in 10-20% of transplants and can be caused by several factors, including improper transplantation technique, extensive invasion of the recipient's bone marrow by tumor cells, and rejection of the transplant. The incidence of bone marrow graft failure is also enhanced by pan-T cell depletion of donor marrow (Mitsuyasu, et al. (1986) Annals of Int. Med. v. 105, p. 20).
The discovery that F 1 mice could reject transplants of parental bone marrow first indicated that NK cells might be involved in the engraftment failures (Cudkowicz et al. (1971) J. Exp Med. V 134, p 83; Cudkowicz et al. (1971) J. Exp. Med. V 134, p 1513; and Kiessling et al. (1977) Eur. J. Immunol. V 7, p 655).
Initially graft rejection was thought to be almost totally dependent on T lymphocytes. However, T cells from an F 1 hybrid animal do not normally attack parental tissue. Therefore, it was suggested that NK cells, not T cells, mediated the rejection of the parental bone marrow.
Additional support for this hypothesis was derived from the observation that mice of a strain normally incapable of rejecting bone marrow transplants acquire this ability when they are injected with cloned NK cells. (Warren et al. (1977) Nature V 300, p 655,). As a result of these findings, Herberman et al. ((1981) Science V 214), p 24 have suggested that suppression of NK activity might lower the incidence of transplant rejection. This suppression should be achieved by treating the recipient with the peptide esters or amides of the present invention prior to transplantation.
Other clinical uses for the present peptide amides or esters consisting essentially of amino acids with hydrophobic side chains, are other situations where NK or CTL are involved in the pathogenesis of disease. In organ transplants in general (kidney, heart, liver, pancreas, skin, etc.), it is widely accepted that cytotoxic T cells are likely to be the cell type responsible for graft rejection (Mayer et al., J. Immunol. V 134, p 258). Thus, it is contemplated that the in vivo administration of peptide esters or amides of the present invention will be of benefit in preventing allograft rejection.
It is also contemplated that peptide esters or amides of the present invention may be of benefit in other spontaneously occurring disease states. A variety of diseases have been classified as "autoimmune diseases" because of the widely accepted relief that they are caused by disorders in the immune system which cause immunologic damage to "self". Thus, in a variety of diseases, including primary biliary cirrhosis, systemic lupus erythematosus, rheumatoid arthritis multiple sclerosis, autoimmune hemolytic anemia, etc., various forms of immunologic damage to selected organs occur. In some of these diseases, such as primary biliary cirrhosis, the histologic abnormalities which occur (in this case in the liver) closely resemble those which occur in GVHD or in rejection of a transplanted liver (Fennel, (1981), Pathol. Annu. V 16 p 289. Thus, it is reasonable that similar mechanisms of cytotoxic lymphocyte damage to liver cells may be occurring, and therefore benefit from therapy with peptide esters or amides of the present invention should also occur in such disease states.
The peptide esters or amides of the present invention should be usable chemotherapeutic agents for patients with natural killer cell tumors (generally leukemias), although very few reports cf these tumors are found in the literature (Komiyama et al. (1982) Blood V 60, p 1428 (1982); Itoh et al. (1983) Blood V 61, p 940; Komiyama et al. (1984) Cancer V 54 p 1547.
It is contemplated that the peptide esters and amides of the present invention may also be used to treat patients with aplastic anemia and other types of bone marrow dysfunction. This suggestion is based on three sets of observations in human studies: first, NK cells can kill normal bone marrow cells (Hansson, et al. (1981) Eur. J. Immunol. V 11, p 8); second NK cells inhibit growth of blood cell precursors in vitro (Hansson, et al. (1982) J. Immunol. V 129, p 126; Spitzer et al.: Blood V 63, p 260; Torok-Storb et al. (1982) Nature V 298, p 473; Mangan, et al. Blood V 63, p 260); and third, NK-like cells with the ability to inhibit the formation of red blood cells with the ability to inhibit the formation of red blood cells have been isolated from patients with aplastic anemia (Mangan, et al. (1982) J. Clin. Invest. V 70, p 1148; and Nogaawa et al. (198I) Blood V 57, p 1025). Moreover, recent studies in the mouse indicate that NK cells may function to suppress hemopoies is in vivo (Holmberg et al. (1984) J. Immunol. V 133, p 2933). However, further investigation is desirable before the connection between NK activity and bone marrow dysfunction is considered conclusive.
Generally, when the peptide esters or amides of the present invention are administered to animals, an effective level is between about 1×10 -4 moles/kg and about 1 ×10 -2 moles/kg.
The following Examples are presented to more fully illustrate preferred embodiments of the present invention and are not intended to limit the invention unless otherwise so stated in the accompanying claims.
Example 1
Cell Preparations and Assays
PBM were separated from heparinized venous blood of healthy donors by centrifuqation over sodium diatrizoate-Ficoll gradients (Isolymph, Gallard-Schlesinger Chemical Mfg. Corp., Carle Place, NY). Monocyte-enriched populations ((MP) were prepared from glass adherent cells and MP-depleted lymphocytes from the nonadherent cells remaining after incubation in glass Petri dishes and passage through nylon wool columns as detailed in Rosenberg et al. (1975) (J. Immunol V 122, pp 926-831). PMN were collected by resuspending peripheral blood cells that penetrated sodium diatrizoate-Ficoll gradients and removing erythrocytes nu dextran sedimentation and hypotonic lysis as previously outlined (Thiele et al. (1985) J. Immunol. V 134, pp 786-793.
All cell exposures to the amino acids, dipeptides or their methyl esters were carried out by suspending cells in Dulbecco's phosphate buffered saline (PBS) and incubating them at room temperature with the reagent at the indicated concentration and time interval. After incubation, the cells were washed twice with Hanks' balanced salt solution and resuspended in medium RPMI 1640 (Inland Laboratories, Forth Worth, TX) supplemented with 10% fetal bovine serum (Microbiological Associates, Walkersville, MN) for assay of function.
Natural killing against K562 target cells was assessed by a 3 hour 51 Cr release assay and percent specific lysis calculated as previously described (Thiele et al. (1985) J. Immunol. 134, pp 786-793). Percent of control cytotoxicity was calculated using the formula: ##EQU1##
Example 2
General Procedures for Generation, Purification and Characterization of L-leucine Methyl Ester and Its Metabolites
MP or PMN (prepared as in Example 1) at a concentration of 25×10 6 per ml were suspended in PBS and incubated with 25 mM Leu-OMe for 20 minutes at 22˜C. Cell suspensions were then centrifuged at 1000 g for 10 minutes and the supernatants harvested and freeze-dried at -70˜C, 100 millitorr atmospheric pressure. In some experiments, Leu-OMe-treated MP or PMN were sonicated to increase the yield of the reaction product. Samples were then extracted with methanol for application to thin layer chromatography (TLC) plates (200 micromolar×20 cm 2 , Analtech, Newark, Del.). Following development with chloroform/methanol/acetic acid (19:1:12.5 by volume), 1 cm bands were eluted with methanol, dried under nitrogen, and resuspended in 1 ml PBS. Mass spectra were obtained with a Finnegan Model 402 automated EI/CI, GS/MS system coupled to an Incos data system. Methane was used as the reagent gas for chemical ionization (CI)mass spectral analysis.
Example 3
Lysosomotropic Substances and
Formation of NK-toxic Products
The addition of Leu-OMe to human PBM was shown to cause rapid death of MP and NK cells but not T or B lymphocytes (Thiele et al. (1985) J. Immunol. V 134, pp 786-793; Thiele et al. (1983) J. Immunol. V 131, pp 2282- 2290). Amino acid methyl esters are known to be lysosomotropic compounds, and in previous studies it was found that the lysosomal inhibitors, chloroquine and NH 4 Cl, prevented Leu-OMe-induced MP toxicity. To assess whether these agents similarly prevented formation of any NK toxic products, the following experiments were carried out, and the results shown in FIG. 1.
PBM (prepared as in Example 1) were incubated with various potential NK toxic agents in the presence or absence of various lysosomal inhibitors for 40 minutes, washed to remove the inhibitor, incubated for 18 hours to permit recovery from any transient inhibition caused by lysosomotropic agents and then tested for NK activity. As can be seen in FIG. 1, neither chloroquine, NH 4 Cl, nor Ile-OMe had any substantial permanent effect on NK function. In contrast, 5 mM Leu-OMe ablated all NK activity. This activity of Leu-OMe was largely prevented by chloroquine, NH 4 Cl, or Ile-OMe. The products generated by MP or PMN, after exposure to Leu-OMe also completely removed all NK activity from PBM. In contrast to the effect noted with Leu-OMe, the lysosomal inhibitors did not protect NK cells from the action of this product(s). Additional experiments indicated that the sonicates of MP or PMN had no effect on NK function in this system whereas the supernatants or sonicates of Leu-OMe treated PMN or MP also depleted NK cells from MP depleted lymphocytes These results therefore suggest that interaction of Leu-OMe with the lysosomal compartment of MP or PMN produced a product which was directly toxic to NK cells through a mechanism that was no longer dependent on lysosomal processing within the NK cell or an additional cell type.
More particularly, the conditions of the manipulations leading to the results shown in FIG. 1 were as follows:
Inhibitors of lysosomal enzyme function prevent generation of an NK toxic product PBM (5×10 6 /ml) or PMN (25× 10 6 /ml) preincubated with 25 mM Leu-OMe for 30 minutes were added to cells Lo be ablated. Cells were incubated with these agents for another 30 minutes at 22° C., then washed and cultured for 18 hours at 37° C. before assay of the ability to lyse K562 cells. Data are expressed as percentage of control cytotoxicity observed with an effector:target ratio of 40:1 (results at other E:T were similar).
Example 4
Ablation of NK Function by PMN produced Leu OMe Product
When the NK toxic properties of MP-Leu-OMe, or PMN-Leu-OMe incubation mixtures were evaluated, it was found that this activity was stable in aqueous solutions for more than 48 hours at 4° C., but labile at 100° C., retarded on Sephadex G-10 columns; dialyzable through 1000 MWCO (molecular weight cut-off) membranes, and could be extracted by chloroform-methanol (3:1, by volume). As shown in FIG. 2, when 14 C-leucine methyl ester was incubated with PMN and the supernatants subsequently separated by TLC, three major peaks of 14 C activity were found. One of these peaks corresponded to leucine methyl ester itself and one to free leucine while the third represented a new product. This third peak accounted for about 10% of the total 14 C-labeled material. When MP-depleted lymphocytes were exposed to each TLC fraction, the third peak was found to contain all NK toxic activity. This NK toxic activity not only appeared to be 14 C labeled but was also ninhydrin positive, suggesting that it was a metabolite which still retained an amino group as well as part of the carbon structure of Leu-OMe. An identical 14 C labeled ninhydrin positive product was detected or TLC of MP-Leu-OMe incubation mixture supernatants or sonicates. The production by PMN or MP of this metabolite was inhibited by chloroquine, NH 4 Cl, or Ile-OMe (data not shown).
Ablation of NK function is mediated by a metabolite of Leu-OMe. PMN (25×10 6 /ml) were incubated with 25 mM 14 C-Leu-OMe for 30 minutes and supernatants harvested for TLC analysis. MP-depleted lymphocytes (2.5×10 6 cells/ml) were exposed to varying dilutions of each TLC fraction for 30 minutes, washed and cultured for 2 hours prior to cytotoxicity assay at E:T. ratio of 20:1. Samples were considered to contain an NK toxic product when percent specific lysis was less than 25% of control. FIG. 2 shows these results.
Example 5
Characterization Of The NK-toxic Metabolite
The nature of the new TLC peak found as described in Example 4 was examined by mass spectroscopy. As shown in FIG. 3A, when the TLC-purified, NK-toxic fraction was subjected to mass spectral analysis, results showing peaks at M/2 259 (MN+), 287 (M+C 2 H 5 +) and 299 (M+C 3 H 5 +)) indicated the presence of a compound of molecular weight 258. The presence of peaks at M/Z 244 (M+--CH ) and 272 (M+C 2 H 5 5 + ---CH 3 ) suggested that this compound contained a methyl ester group. Furthermore, the persistence of peaks corresponding to leucine (MN+=131, M+C 2 H 5 =159) and leucine methyl ester (MH+=146, M+C 2 H 5 =174), in spite of careful TLC purification of the NK toxic product from any free leucine or Leu-OMe present in the crude supernatants of the incubation mixtures, suggested that a condensation product of Leu-OMe such as Leu-Leu-OMe (MW258) was present in the NK toxic fraction isolated after incubation of PMN or MP with Leu-OMe.
When Leu-Leu-OMe was synthesized from reagent grade Leu-Leu, by incubation in methanol hydrochloride, it was found to have TLC mobility identical to NK toxic fractions of MP-Leu-OMe or PNM-Leu-OMe incubation mixtures. Furthermore, its CI mass spectrum as shown in FIG. 3B was identical to that of the 258 molecular weight compound found in these incubation fractions.
Experiments further confirmed that Leu-Leu-OMe was the product generated by MP or PMN from Leu-OMe that was responsible for the selective ablation of NK function from human lymphocytes. Leu-Leu-OMe was synthesized by addition of Leu-Leu to methanolic HCl. TLC analysis revealed less than 2% contamination of this preparation with leucine, Leu-Leu, or leu-OMe, and CI mass spectral analysis (FIG. 3B) revealed no contaminants of other molecular weights.
FIG. 3A shows the chemical-ionization CI mass spectra of TLC fractions with NK toxic activity as described in FIG. 2, and also of Leu-Leu-OMe synthesized from reagent grade Leu-Leu (FIG. 3B).
Example 6
In the representative experiments shown in FIG. 4, MP-depleted lymphocytes were exposed to varying concentrations of Leu-Leu-OMe for 15 minutes at room temperature, then washed and assayed for ability to lyse K562 cells. No NK function could be detected in lymphocyte populations exposed to greater than 50 micromolar Leu-Leu-OMe. As previously demonstrated (Thiele et al. (1983) J. Immunol. V 131 pp2282-2300), exposure of such MP-depleted lymphocyte populations to 100 fold greater concentration of leucine or leu-OMe had no irreversible effect on NK function Leu-Leu or the D-stereoisomer, D-Leu-D-Leu-OMe, also had no inhibitory effect. While Leu-Leu-Leu-OMe caused dose-dependent loss of NK function, 5fold greater concentrations of this tripeptide methyl ester were required to cause an effect equivalent to that of the dipeptide methyl ester of L-leucine. When lymphocyte populations exposed to varying concentrations of Leu-Leu-OMe were further analyzed, it was found that exposure to more than 50 micromolar Leu-Leu-OMe resulted in the loss of K562 target binding as well as complete depletion of cells stained by an anti-NK cell monoclonal antibody Leu 11b. Thus, the MP-or PMN-generated product of Leu-OMe which is directly toxic for human NK cells is the dipeptide condensation product Leu-Leu-OMe.
The condition of the manipulations resulting in the data leading to FIG. 4A and 4B are further detailed as follows: for loss of NK function after exposure to Leu-Leu-OMe, MP-depleted lymphocytes (2.5×10 6 cells/ml) were incubated for 15 minutes with the indicated concentrations of leucine containing compounds. Cells were then washed, cultured at 37˜C for2 hours (FIG. 4A) or 18 hours (Expt. 2FIG. 4B) and then assayed for NK activity. Results are given for E:T ratio of 20:1.
Example 7
NK Ablation by a Variety of Dipeptide Methyl Esters
In previously reported studies, Leu-OMe was unique among a wide variety of amino acid methyl esters in its ability to cause MP or PMN dependent ablation of NK cell function from human PBM (Thiele et al. (1985) J. Immunol. V 134, pp 786-793). The identification of Leu-Leu-OMe as the MP-generated metabolite responsible for this phenomenon suggested that either MP/PMN did not generate the corresponding dipeptide methyl esters in toxic amounts from other amino acids, or that Leu-Leu-OMe was unique among dipeptidemethyl esters in its toxicity for NK cells. Therefore, experiments were carried out to assess the effect of other dipeptide methyl esters on NK cell function. The methyl esters of a variety of dipeptides were synthesized and analyzed for the capacity to deplete NK cell function. Each dipeptide methyl ester was assessed in a minimum of three experiments. As is shown by the results displayed in FIG. 5, Leu-Leu-OMe is not the only dipeptide methyl ester which exhibits NK toxicity. When amino with hydrophobic side chains were substituted for leucine in either position, the resulting dipeptide methyl ester generally displayed at least some degree of NK toxicity. In particular, Leu-Phe-OMe, Phe-Leu-OMe, Val-Phe-OMe and Val-Leu-OMe produced concentration-dependent ablation of NK function at concentrations comparable to those at which Leu-Leu-OMe was active. The sequence of active amino acids was important, however, as evidenced by the finding that Phe-Val-OMe was markedly less active than Val-Phe-OMe. Similarly, Leu-Ala-OMe was NK inhibiting, whereas 10-fold greater concentrations of Ala-Leu-OMe had no NK inhibitory effects. Furthermore, Phe-Phe-OMe was less NK toxic than either Leu-Phe-OMe or Phe-Leu-OMe and Val-Val-OMe was less active than either Leu-Val-OMe or yet Val-Phe-OMe was among the most potent of toxic dipeptide methyl esters. Thus, conformational aspects of the dipeptide methyl ester amino acid side also seem to be of importance in producing the levels of observed NK toxicity.
When amino acids with hydrophilic, charged or hydrogen side chains were substituted for leucine, the resulting dipeptide esters either had greatly reduced NK toxicity, as in the case of Gly-Leu-OMe or Leu-Gly-OMe, or no observed NK inhibitory effects, as in the case of Leu-Arg-OMe, Leu-Tyr-OMe Ser-Leu-OMe, Lys-Leu-OMe or Asp-Phe-OMe. Furthermore, when the D-stereoisomer was present in either position of a dipeptide methyl ester, no toxicity was observed for NK cells (FIG. 5). When unesterified dipeptides were assessed for their effect on NK function, as in the case of Leu-Leu (FIG. 4), up to 5 ×10 -3 M concentrations of Leu-Phe, Phe-Leu, Val-Leu, and Val-Phe had no effect on NK cell survival or lytic activity.
D-Leu-D-Leu-OMe had no effect on Leu-Leu-OMe mediated NK toxicity although high levels of zinc appeared to inhibit this Leu-Leu-OMe toxicity.
Previous experiments had demonstrated that compounds such as Val-OMe, Phe-OMe, or combinations of Val-OMe and Phe-OMe did not delete NK function from human PBM (Thiele et al. (1985) J. Immunol. V 134, pp 786-793), despite the current finding that dipeptide methyl esters containing these amino acids were potent NK toxins. In order to determine whether MP or PMN could generate the relevant dipeptide methylesters from these amino acid methyl esters, TLC analysis of the supernatants of MP and PMN incubated with these compounds was carried out. It was found that MP and PMN did generate detectable amounts of dipeptide methylesters from these L-amino acid methyl esters. However when equal concentrations of Leu-OMe, Val-OMe, or Phe-OMe were added to MP or PMN, the concentrations of Val-Val-OMe generated were 50 to 80% of those found for Leu-Leu-OMe, while Phe-Phe-OMe was detected at only 10-30% of the levels of Leu-Leu-OMe. Dipeptide methyl esters were not generated from D-amino acid methyl esters.
FIG. 5 shows the NK toxicity of dipeptide methyl esters. MP-depleted lymphocytes were treated with varying concentrations of dipeptide methyl esters as outlined in FIG. 4. Results are given for the mean ±SEM of at least 3 separate experiments with each compound.
Example 8
NK Toxicity of an Artificially
Hydrophobic Dipeptide Methyl Ester
Beta methyl aspartyl phenylalanine was prepared by methanolic hydrochloride methylation of aspartyl phenylalanine methyl ester. The NK toxicity of both aspartyl phenylalanine methyl ester and beta methyl aspartyl phenylalanine methyl ester was measured as described for the dipeptide methyl esters in Example 7. As the data in Table 2 indicates, when the polar side chain of the aspartyl amino acid dipeptide component is esterified with a methyl group, this being a conversion from relative hydrophilicity to substantial hydrophobicity, NK toxicity becomes apparent. Although yet not as toxically effective as a number of the hydrophobic-type dipeptides in Example 7, the data in Table 2 indicate that a dipeptide methyl ester comprising synthetic hydrophobic (lipophilic) amino acids may be used to inhibit NK function.
TABLE 2______________________________________L-ASPARTYL (beta-METHYL ESTER)-L-PHENYLALA-NINE METHYL ESTER IS NK TOXIC WHILE L-ASPAR-TYL-L-PHENYLALANINE METHYL ESTER IS NOT NK FunctionPreincubation % Specific Cytotoxicity______________________________________Nil 50.8Asp--Phe--OMe:100 micromolar 54.2250 micromolar 45.7500 micromolar 45.71000 micromolar 46.9Asp--(beta-OMe)--Phe--OMe:100 micromolar 38.9250 micromolar 13.9500 micromolar 2.81000 micromolar -0.1______________________________________
Example 9
In Vivo Effects on Cytotoxic Cell Function
Leu-Leu-OMe or Leu-Phe-OMe were suspended in PBS, pH 7.4. Then individual C3H/HeJ mice (25 gram size) were administered by tail-vein injection either 2.5×10 -5 moles (6.5 mg) of Leu-Leu-OMe, 2.5×10 -5 moles (7.1 mg) Leu-Phe-OMe, or an equal volume of the PBS diluent, this dose being about 1×10 -3 moles per kg. For 15-30 minutes post-injection, Leu-Leu OMe and Leu-Phe OMe-treated animals but not the control animals exhibited decreased activity and an apparent increase in sleep. Subsequent to this quiescent period no difference in activity or appearance in the mice was noted. Two hours post-injection, the mice were sacrificed and their spleen cells were assayed for NK function in a standard 4 hour assay against YAC-1 tumor targets. In all mice, total cell recovery ranged from 1×10 8 to 1.1×10 8 spleen cells per animal. As noted in Table 3, the control mouse spleen cells exhibited greater killing at 25:1 and 50:1 effector to target cell ratios than did the spleen cells of treated mice at 100:1 and 200:1 E/T, respectively. Thus, Leu-Leu-OMe or Leu-Phe-OMe caused a greater than 75% decrease in splenic lytic activity against YAC-1 tumor targets.
TABLE 3______________________________________Cytotoxic Cell Function Effector:Target Ratio 25:1 50:1 100:1 200:1 Percent lysis of target cells______________________________________Control 8.29 12.88 20.60 29.29Leu--Leu--OMe 2.37 4.58 7.12 12.77Leu--Phe--OMe 3.89 4.68 6.91 11.91______________________________________
Example 10
Differential Sensitivity of Natural Killer Cells (NK) and Mononuclear Phagocytes (MP) to Leucylleucine-Methyl Ester (Leu-Leu-OMe)
In the experiments depicted in FIG. 6, freshly isolated PBM (2.5×10 6 /ml PBS and 1 g/l glucose) were incubated at room temperature with varying concentrations of Leu-Leu-OMe. After a 15 minute exposure to this compound, the cells were washed, incubated for 2 hours at 37° C. and then assessed for the percentage of remaining viable cells which were stained by anti-MP or anti-NK monoclonal antibodies. Preincubation with greater than 25-50 micromolar Leu-Leu-OMe led to loss of NK cells. This concentration of Leu-Leu-OMe did not deplete MP from PBM but higher concentrations of Leu-Leu-OMe caused loss of MP. The data is FIG. 6 show these results.
Anti-MP monoclonal antibodies (63D3) and anti-NK monoclonal antibodies (leu 11b) were obtained from Becton Dickinson Monoclonal Center, Inc., Mountain View, CA. The antibody staining and Fluorescence Activated Cell Sorter (FACS) procedure was that of Rosenberg et al. (1981) (J. Immunol. V 126, p 1473). Data are expressed as percent of antibody staining in control cells (mean±SEM, n=4).
Example 11
Effects of Leu-Leu-OMe on a Variety of Cell Types
While it was clear that a substantial percentage of lymphocytes remained viable following exposure to even 1 mM Leu-Leu-OMe, the finding that disparate cell types such as MP and NK were both susceptible to Leu-Leu-OMe mediated toxicity raised the possibility that this agent was a non-specific cell toxin. Therefore, the series of experiments depicted in FIG. 7 was performed to assess other cell types for evidence of toxicity following exposure to Leu-Leu-OMe.
To facilitate screening of multiple cell types for evidence of cell death following exposure to Leu-Leu-OMe, a 51 Cr release assay was devised. In preliminary experiments it was noted that 51 Cr release from MP-enriched populations exposed to varying concentrations of Leu-Leu-OMe correlated very, closely with concentration-dependent loss of anti-Mp antibody staining cells from PBM after similar incubation. Following brief exposures to Leu-Leu-OMe at room temperature, the loss of anti-MP antibody staining cells from PBM or the release of 51 Cr from MP-enriched populations was always detectable within a 30 to 60 minute period of culture at 37° C. and maximal effects were seen within 3 to 4 hours.
Therefore, 51 Cr release in a 4 hour assay was used in these experiments to assess toxicity from Leu-Leu-OMe. As shown in the first graph of FIG. 7, when the whole PBM population was exposed to varying concentrations of Leu-Leu-OMe, detectable 51 Cr release was observed after exposure to 25 to 50 micromolar Leu-Leu-OMe, but only upon exposure to greater than 100 micromolar Leu-Leu-OMe was the maximal achievable 51 Cr release from PBM observed. When MP-enriched adherent cells (AC) were similarly assessed, minimal 51 Cr release was observed after exposure to 25-50 micromolar Leu-Leu-OMe whereas upon incubation with higher concentrations of this agent, more 51 Cr release from AC was observed than with PBM. When nylon wool non-adherent lymphocytes (NAC) were assessed, small but significant 51 Cr release was observed with 25 to 50 micromolar Leu-Leu-OMe. When NAC were exposed to increasing concentrations of Leu-Leu-OMe, greater quantities of 51 Cr release were observed. N-SRBC positive cells showed a dose-dependent Leu-Leu-OMe induced 51 Cr release pattern indistinguishable from that of NAC. Since both antibody staining (FIG. 6) and functional studies (FIG. 4) have shown that 100 micromolar Leu-Leu-OMe causes maximal depletion of NK, this finding suggested that other lymphocytes were also susceptible to Leu-Leu-OMe toxicity at concentrations greater than 100 micromolar. When T4 enriched populations of T cells were assessed, however, it was clear that even 1000 micromolar Leu-Leu-OMe caused minimal 51 Cr release from this population. In contrast, when N-SRBC positive cells were depleted of OKT4 positive cells, the remaining T8-enriched population produced high levels of 51 Cr release following exposure to Leu-Leu-OMe.
When cell lines of myeloid or lymphoid origin were similarly assessed, selective toxicity of Leu-Leu-OMe was again observed. The human T cell leukemia line MoLT-4 demonstrated no detectable Leu-Leu-OMe toxicity over a broad concentration range. The human plasma cell lines HS-Sultan and the B lymphoblastoid line Daudi demonstrated no significant 51 Cr release or alteration in subsequent proliferative rate (data not shown) after exposure to a broad range of Leu-Leu-OMe concentrations. When the susceptibility of EBV-transformed B cell lines or clones to this agent was assessed, no significant toxicity of less than 250 micromolar Leu-Leu-OMe was seen. However, with higher concentrations of Leu-Leu-OMe, a variable degree of toxicity was seen. Some EBV lines consistently displayed less than 20% 51 Cr release even after exposure to 1 mM Leu-Leu-OMe, while other lines produced 25-35% 51 Cr release after exposure to 250 micromolar Leu-Leu-OMe. In contrast, the human cell line U937 was susceptible to concentration-dependent Leu-Leu-OMe toxicity in a pattern indistinguishable from that of the peripheral blood MP with which this cell line shares many phenotypic and functional characteristics. After exposure to more than 250 micromolar Leu-Leu-OMe, extensive 51 Cr release was observed and no viable proliferating U937 cell could be detected (data not shown). Similarly, the erythroleukemia line K562 demonstrated no significant 51 Cr release or alteration in subsequent proliferative rate (date not shown) upon exposure to 100 micromolar or lower concentrations of Leu-Leu-OMe. With higher concentrations of Leu-Leu-OMe, modest amounts of 51 Cr release and partial loss of proliferative capacity were observed data not shown). In contrast, a variety of cell types of non-lymphoid, non-myeloid origin including human umbilical vein endothelial cells, the human renal cell carcinoma line, Currie, the human epidermal carcinoma line, HEp-2, and human dermal fibroblasts demonstrated nc significant Leu-Leu-Ome induced 51 Cr release. Furthermore, incubation of each of these non-lymphoid cell types with 500 micromolar Leu-Leu-OMe had no discernible effect on subsequent proliferative capacity (data not shown).
HS-Sultan, a human plasma cell line (Goldblum et al. (1973) Proc. Seventh Leucocyte Culture Conference, ed by Daguilland, Acad. Press NY. pp 15-28), Daudi, a B lymphoblastoid cell line (Klein et al. (1968) Cancer Res. V 28, p 1300), MoLT-4, an acute lymphoblastic T-cell leukemia line (Monowada et al. (1972) J. Nat'l. Canc. Inst. V 49, p 891), and U-937, a human monocyte-like call line (Koren et al. (1979) Nature V 279, p 891) were obtained from the American Type Culture Collection, Rockville, MD. These lines as well as HEp-2 a human epidermoid carcinoma line (a generous gift of Dr. R. Sontheimer, UTHSCD); Currie, a human renal cell carcinoma line (a generous gift of Dr. M. Prager, UTHSCD); and K562, a human erythroleukemia line (a generous gift of Dr. M. Bennett, UTHSCD) were maintained in culture in medium RMPI supplemented with 10% FBS. Human dermal fibroblasts (a generous gift of Dr. T. Geppert, UTHSCD) were serially passaged in culture as well while human umbilical vein endothelial cells (a generous gift of Dr. A. Johnson, UTHSCD) were used after one subculture. Epstein Barr virus (EBV) transformed B lymphoblastoid cell lines JM.6 and SM.4 ,kindly provided by Dr. J. Moreno, UTHSCD) and cloned EBV transformed B cell lines SDL-G2 and D8-219 (a generous gift of Drs. L. Stein and M. Dosch, Hospital for Sick Children, Toronto, Canada) were maintained in culture in medium RPMI supplemented with 10% FBS.
In some experiments, toxicity of Ler-Leu-OMe for a variety of cell populations was assessed by 51 Cr release. In assays where cells obtained from suspension culture were to be used, cells were labeled with Na 2 51 CrO 4 (ICN, Plainview, NY) for 60-90 minutes at 37° C. and then washed three times. Cells were then suspended in PBS (2 5×10 6 /ml) and incubated in microtiter plates, 50 microL/well with indicated concentrations of Leu-Leu-OMe for 15 minutes at room temperature. In assays where cells were obtained from monolayer cultures, microtiter wells hours at 37˜C. Cells were then labeled with Na 2 51 CrO 4 while in adherent culture. Following 51 Cr labeling, wells were thoroughly washed and varying concentrations of Leu-Leu-OMe added in 50 microL PBS and the plates incubated for 15 minutes at room temperature.
Following such initial serum-free incubations, 200 microL/well of medium RPMI containing 10% FBS were added and the plates incubated for another 4 hours prior to removal of 100 microliters of supernatant. Radioactivity in the supernatant was measured in an auto-gamma scintillation spectrometer (Packard Instrument Co., Downers Grove, IL). The percent specific release was calculated from the formula: ##EQU2## in which maximal release refers to cpm obtained in wells containing 50% lysing agent (American Scientific Products, McGraw Park, IL) and spontaneous release refers to cpm released by cells incubated in control medium in the absence of Leu-Leu-OMe or the lysing agent. Only experiments in which spontaneous release was 25% were used for subsequent data interpretation.
While the MP-like tumor line U937 was virtually identical to MP in susceptibility to Leu-Leu-OMe, none of the non-lymphoid, non-myeloid cell lines tested demonstrated such susceptibility to Leu-Leu-OMe mediated toxicity.
The current example demonstrates that at concentrations 10 to 20 fold greater than those at which cytotoxic cells are ablated, Leu-Leu-OMe does have some minimal toxicity for certain non-cytotoxic lymphoid cells such as EBV transformed B cells and K562 cells. Yet, while it is impossible to exhaustively exclude the possibility that certain non-cytotoxic cells might also be equally sensitive to Leu-Leu-OMe-mediated toxicity, ar present the ability to function as a mediator of cell mediated cytotoxicity is the one unifying characteristic of the cell types which are rapidly killed by exposure to Leu-Leu-OMe.
In developing the data expressed in FIG. 7, cells (2.5×10 6 /ml) were exposed to the indicated concentrations of Leu-Leu-OMe for 15 minutes at room temperature, then specific 51 Cr release during the next four hours was assessed. Data for the EBV transformed lines JM.6, SDL-G2, D8-2I9, and SM.4, respectively, are shown in order from top to bottom.
Example 12
Relative Sensitivity of CTL and NK to Leu-Leu-OMe
Experiments were also designed to assess the relative sensitivity of NK and CTL to Leu-Leu-OMe. In the studies detailed in FIG. 8 and 9, cytotoxicity assays were performed over a broad range of E:T ratios and units of lytic activity arising from equal numbers of responding lymphocytes were calculated and compared. As shown in FIG. 8, both spontaneous NK and precursors of activated NK were totally eliminated by exposure to 100 micromolar Leu-Leu-OMe while CTL precursors, though diminished, were generally still present at greater than 50% of control levels. Only after exposure to greater than 250 micromolar Leu-Leu-OMe were all CTL precursors eliminated.
FIG. 8 shows that incubation with Leu-Leu-OMe eliminates precursors of cytotoxic T lymphocytes (CTL) and activated NK-like cells (AcNK). Non-adherent lymphocytes (2.5×10 6 /ml) were incubated with the indicated concentrations of Leu-Leu-OMe for 15 minutes. Cells were then Washed and either placed in mixed lymphocyte culture or assayed for specific lysis of K562 cells (NK). After 6 day MLC, cells were assayed for specific lysis of allogeneic stimulator lymphoblasts (CTL) or K562 (AcNK). Data are expressed as percent of control lytic units (mean+ SEM, n=6).
When the elimination of CTL and activated NK precursors by Leu-Leu-OMe was compared to that of spontaneous NK, the mean Leu-Leu-OMe concentration required to diminish lytic activity by 75% was significantly greater for elimination of CTL precursors (123±25 micromolar) than for elimination of precursors of activated NK (50±5 micromolar, p 0.05). Both values were also higher than the mean concentration of Leu-Leu-OMe required to diminish spontaneous NK lytic activity by 75% (35 micromolar±4 micromolar). FIG. 9 shows that, following activation, CTL and AcNK became identical in sensitivity to Leu-Leu-Me. After 6 day MLC, cells were incubated for 15 minutes with the indicated concentrations of Leu-Leu-OMe, then assayed for CTL or AcNK activity as for FIG. 8. Thus, only after MLC activation did CTL display a sensitivity to Leu-Leu-OMe toxicity that was equal to that of NK cells.
Example 13
Mechanism of Leu-Leu-OMe
Prior Example's demonstrated that incubation of mixed lymphoid cell populations with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) results in selective loss of NK cells and precursors of cytotoxic T cells whereas B cell and T helper cell function is relatively preserved. Of note, use of Leu-Leu-OMe to remove donor cytotoxic lymphocytes has been shown to be of benefit in preventing lethal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation. The present example involves elucidation of the mechanism whereby Leu-Leu OMe kills cytotoxic lymphocytes.
Human peripheral blood lymphocytes (PBL) were incubated in the presence of [ 3 H]labeled Leu-Leu-OMe at 22° C. for varying lengths of time. The incubation mixture was then centrifuged through silicone oil to separate the cells from any unbound or non-internalized [ 3 HLeu-Leu-OMe. As demonstrated in FIG. 10, the quantity of cell-associated [ 3 H]Leu-Leu-OMe increased in a linear, time-dependent fashion over the first 30 minutes of incubation. As demonstrated in Table 4, when incubations were performed at temperatures below 4° C., no accumulation of [ 3 H]Leu-Leu-OMe by PBL was observed. At 37° C., levels of [ 3 H]Leu-Leu-OMe accumulation by PBL were increased above those seen at 22° C. (see Table 4). These findings suggested that Leu-Leu-OMe was not simply binding to PBL by an energy (temperature) independent process. The time and temperature dependent increases in cell-associated [ 3 H]labeled Leu-Leu-OMe suggested that this compound was being internalized and retained by PBL.
TABLE 4______________________________________TEMPERATURE DEPENDENCE OF [.sup.3 H]LEU--LEU--OMEUPTAKE/BINDING BY LYMPHOCYTES [.sup.3 H]Leu--Leu--OMe Uptake/BindingExpt. Temperature (micro-moles/10.sup.6 cells)______________________________________1 0° C. 0.05 22° C. 0.772 4° C. 0.02 22° C. 0.31 37° C. 0.52______________________________________
When the concentration dependence of Leu-Leu-OMe uptake by PBL was assessed (see FIG. 11), the quantity of [ 3 H]Leu-Leu-OMe incorporated per unit of time was noted to increase in direct proportion to external concentrations until near maximal uptake was noted with approximately 250-500 micro-M. The findings detailed in FIG. 11 indicate the uptake of Leu-Leu-OMe observed after a 15 minute incubation performed at 22° C. The data indicate that under these conditions the Vmax of (maximum velocity) this process is approximately 10 -10 moles/minute/10 6 cells, whereas the Km is approximately 10 -4 M. These findings indicate that this process is saturable and therefore a facilitated transport mechanism is likely to be involved in the uptake of Leu-Leu-OMe by PBL. As demonstrated by the results displayed in Table 5, [ 3 H]Leu-Leu-OMe uptake by PBL is competitively inhibited not only by excess quantities of unlabeled Leu-Leu-OMe, but also by high concentrations of the dipeptide Leu-Leu and by other esters of Leu-Leu such as Leu-Leu-OBenzyl.
TABLE 5______________________________________COMPETITIVE INHIBITION OF [.sup.3 H]LEU--LEU--OMEUPTAKE BY OTHER DERIVATIVES OF LEU--LEUUnlabeled % Inhibition ofCompound* [.sup.3 H]Leu--Leu--OMe Uptake.sup.+______________________________________L-Leu--OMe -10L-Leu--Leu 44L-Leu--L-Leu--OMe 72D-Leu--D-Leu--OMe 7L-Leu--L-Leu--OBenzyl 87L-Leu--L-Leu--NH.sub.2 8L-Leu--L-Leu--L-Leu--OMe 6______________________________________ *250 microM .sup.+ 10 microM
However, the amide derivative of Leu-Leu (L-Leu-L-Leu-NH 2 ); the D-stereoisomer containing dipeptide ester, D-Leu-D-Leu-OMe; the amino acid analog Leu-OMe; and the tripeptide analog Leu-Leu-Leu-OMe do not competitively inhibit PBL uptake of L-Leu-L-Leu-OMe. Thus, the facilitated transport process utilized by PBL in the uptake of Leu-Leu-OMe appears to be relatively specific for L-stereoisomers of dipeptides or dipeptide esters.
As detailed in Table 6, competitive inhibition of Leu-Leu-OMe uptake is seen with some but not all dipeptide methyl esters composed of L-stereoisomers of naturally occurring amino acids.
TABLE 6______________________________________COMPETITIVE INHIBITION OF [.sup.3 H]LEU--LEU--OMEUPTAKE BY OTHER DIPEPTIDE ESTERS % Inhibition NKUnlabeled of [.sup.3 H]Leu--Leu--OMe ToxicityCompound* Uptake.sup.+ (LD.sub.50)______________________________________Pro--Leu--OMe -18 >250 micro-MAsp--Phe--OMe 8 >250 micro-MLeu--Leu--OMe 72 35 micro-MLeu--Phe--OMe 72 29 micro-MLeu--Tyr--OMe 86 >250 micro-MVal--Phe--OMe 75 24 micro-MSer--Leu--OMe 94 >250 micro-M______________________________________ *250 microM .sup.+ 10 microM
As previously reported, (see prior examples and PNAS 1985; 82:2468-2472), incubation of PBL for 15 minutes at 22° C. with a variety of dipeptide methyl esters leads to loss of all natural killer cell (NK) function because of the direct toxicity of these compounds for cytotoxic lymphocytes. Concentrations of various dipeptide esters which result in 50% loss of human NK function (LD 50 ) are detailed in the last column of Table 6. Of note, all compounds with significant NK toxicity at concentrations below 250 micron-M appear to be taken up by the same facilitated transport process as evidenced by significant competitive inhibition of [ 3 H] Leu-Leu-OMe uptake. This transport process is not competitively inhibited by some dipeptide esters such as Pro-Leu-OMe or Asp-Leu-OMe. These latter dipeptide esters also exhibit no NK toxicity. Such lack of NK toxicity may be related to lack of accumulation of such agents by NK cells. However, other dipeptide esters such as Leu-Tyr-OMe or Ser-Leu-OMe which display little or no toxicity for NK cells may be, nevertheless, excellent competitive inhibitors of [ 3 H]Leu-Leu-OMe uptake. These findings suggested that characteristics other than capacity for uptake by lymphocytes are likely to be involved in the selective NK toxicity of Leu-Leu-OMe and other dipeptide methyl esters. Whereas uptake by this pathway appears to be necessary for NK cytotoxicity, it is not always sufficient.
Additional experiments, detailed in Table 7, were performed to assess the metabolic fate of [ 3 H]Leu-Leu-OMe within PBL. Cells were incubated with [ 3 H]Leu-Leu-OMe for 15 minutes at 22° C. to permit uptake of this compound and then were washed. If the cells were immediately lysed and 10% trichloroacetic acid (TCA) was added to precipitate higher molecular weight cell proteins and nucleic acids, essentially all of the [ 3 H]label remained in the supernatant as anticipated for a small molecular weight peptide which is soluble in 10% TCA. However, as shown in Table 7, if [ 3 H]Leu-Leu-OMe-loaded PBL ware incubated at 37° C. for 15 to 60 minutes prior to cell lysis, an increasing fraction of the [ 3 H] precipitated in 10% TCA.
TABLE 7______________________________________[.sup.3 H]LEU--LEU--OME IS CONVERTEDTO A PRODUCT WHICH PRECIPITATESIN THE PRESENCE OF 10% TCA [.sup.3 H]Leu--Leu--OMeDuration of Initial Duration of Second Total TCA Prec.22° C. Incubation 37° C. incubation cpm × 10.sup.-3______________________________________15 minutes 0 61.4 0.5 15 minutes 24.9 6.8 30 minutes 20.6 12.7 60 minutes 12.7 10.7______________________________________
In other experiments it was noted that addition of proteinase K (e.g. Protease Type XXVIV from Triterochium album, Sigma Chemical Company, St. Louis, Mo.) to the cell lysate prior to TCA precipitation resulted in loss of all [ 3 H]label from the precipitate. These findings suggested that, within the first hour after [ 3 H]Leu-Leu-OMe uptake by PBL, a significant fraction of this peptide or its amino acid components was incorporated into a higher molecular weight form which was insoluble in 10% TCA.
As shown by the data displayed in Table 8 [ 3 H]Leu-Leu-OMe was found to be metabolized differently within various cell populations.
TABLE 8______________________________________PRODUCTION OF A TCA PRECIPITABLE PRODUCTFROM [.sup.3 H]LEU--LEU--OME DOES NOT CORRELATEWITH LEVELS OF INITIAL [.sup.3 H]LEU--LEU--OMEINCORPORATION [.sup.3 H]Leu--Leu--OMe Incorporation TCA Precipitate Initial (% ofExpt. Cell Type cpm cpm initial)______________________________________1 Non-adherent 27,870 2,341 8.4% Lymphocytes LLMe Resistant 7,184 50 0.7% Lymphocytes2 T4 Cells 12,200 207 1.7% T8, NK Cells 22,753 3,208 14.1% Fibroblasts 63,229 293 0.5% Renal Cell 35,855 267 0.7% Carcinoma______________________________________
In experiment 1 of Table 8 non-adherent peripheral blood lymphocytes were incubated in the presence or absence of 250 micro-M unlabeled Leu-Leu-OMe for 15 minutes and then cultured overnight at 37° C. This form of exposure to Leu-Leu-OMe has been shown previously herein to result in loss of NK cells and a substantial fraction of CD8(+) T cells, whereas the majority of CD4(+) lymphocytes are resistant to any toxic effects of this agent and remain viable and functionally intact. As shown by the data displayed in Table 8, when these cells were then incubated with [ 3 H]labeled Leu-Leu-OMe for 15 minutes at 22° C., both populations of lymphocytes were observed to take up this compound although uptake by Leu-Leu-OMe (LLMe) resistant lymphocytes was significantly reduced. However, when production of a product which precipitated in 10% TCA was assessed following a second incubation at 37° C. for 30 minutes, it was noted that the LLMe resistant subset of lymphocytes produced almost no detectable amounts of this as yet unidentified product.
In experiment 2 (Table 8), PBL were divided into a CD4(+) T cell (T4 cell)-enriched population and a T8, NK-enriched population by staining with anti-CD4 or anti-CD8 monoclonal antibodies and panning on goat anti-mouse coated petri dishes to enrich for the unstained lymphocyte subsets as previously described (see prior Examples and J. Immunol. 1986 136:1038-1048). Again, it was noted that T4 cells took up less [ 3 H]Leu-Leu-OMe during an initial incubation than did a population of lymphocytes enriched for T8 and NK cells. However, the differences in production of a product which precipitated in 10% TCA were even more dramatic. Whereas initial [ 3 H]Leu-Leu-Me uptake by T4 cells was approximately 53% of that seen with an equal number of T8 and NK cells, the amount of [ 3 H]label appearing in a 10 % TCA precipitate of the T4 cell sonicate after a subsequent 30 minute incubation was less than 7% of the quantity noted in the TCA precipitable of T8 and NK cell sonicates. Furthermore, little or no TCA insoluble product was produced by other non-lymphoid cell types such as dermal fibroblasts or a renal cell carcinoma line, Cur, which have been previously noted to be resistant to the toxicity of Leu-Leu-OMe (J. Immunol. 1986; 136:1038-1048). These findings, therefore, suggested an association between Leu-Leu-OMe toxicity and intracellular production of a presumably higher molecular weight product from [ 3 H]Leu-Leu-OMe that was insoluble in 10% TCA. As proteinase K digestion removed this product, it was likely to be a larger peptide or protein into which [ 3 H]Leu had been incorporated.
In additional experiments detailed in Table 9, it was noted that synthesis of this TCA precipitable material from Leu-Leu-OMe was not inhibited by a concentration of cycloheximide known to block ribosomal protein synthesis. This finding suggested that extraribosomal pathways of peptide or protein synthesis were likely to be involved in this process. A variety of proteases and peptidases have been noted to catalyze transpeptidation reactions when incubated with large concentrations of dipeptide esters (J. Biol. Chem. 1952; 195:645-656). When agents known to inhibit various forms of protease activity were added during incubations of PBL with [ 3 H]Leu-Lau-OMe, it was noted that the serine protease inhibitor, phenylmethylsulfonylfluoride (PMSF) did not inhibit generation of TCA insoluble material (Expt. 1, Table 9). Furthermore, levels of [ 3 H]label in TCA precipitates actually increased when NH 4 Cl was added at concentrations known to increase lysosomal pH and thereby inhibit the action of many lysosomal proteases (Expt 2, Table 9). However, iodoacetamide almost completely inhibited synthesis of a TCA insoluble product of [ 3 H]Leu-Leu-OMe (Expt. 1 and 2, Table 9). Iodoacetamide nonspecifically binds covalently to free sulfhydryl groups and thereby inhibits thiol protease function as well as other enzymatic reactions dependent on the presence of reduced sulfhydryl groups.
TABLE 9______________________________________PRODUCTION OF A TCA INSOLUBLEPRODUCT FROM [.sup.3 H]LEU--LEU--OME:EFFECT OF VARIOUS INHIBITORS [.sup.3 H]Leu--Leu--OMe Incorporation 10%Inhibitor Initial TCA PrecipitateExpt. (conc.) cpm______________________________________1 Nil N.D. 2,160 ± 193 Cycloheximide, N.D. 2,726 ± 132 (100 micro-g/ml) PMSF, 1 micro-M N.D. 2,078 ± 213 Iodoacetamide N.D. 140 ± 5 (0.5 micro-M)2 Nil 6,139 ± 293 1,517 ± 248 Iodoacetamide, 6,316 ± 188 243 ± 16 (0.5 micro-M) NH.sub.4 Cl, 5,746 ± 1,272 3,275 ± 261 (15 micro-M)3 Nil 8,751 ± 106 1,015 ± 145 Gly--Phe--CHN.sub.2, 8,691 ± 522 104 ± 55 (10.sup.-6 M)______________________________________
Of note, however, glycylphenylalanine diazomethane (Gly-Phe-CHN 2 ), a selective and highly specific inhibitor of the thiol protease, dipeptidyl peptidase I (Cathepsin C) (J. Biol. Chem. 1981; 256:1923-1928) was similarly effective in blocking synthesis of a TCA insoluble product of [ 3 H]Leu-Leu-OMe. Dipeptidyl peptidase I has previously been noted to be present at high levels in the spleen of various mammals (Proteinases in Mammalian Cells and Tissues, 1977; A. J. Barrett, ed., North-Holland Publishing Col, p. 314-322) and to be present in detectable levels in human peripheral blood (Biol. Soc. Trans. 1974; 2:432-434).
As detailed in Table 10, when lymphocyte subsets were highly purified in fluorescence activated cell sorting and then analyzed for dipeptidyl peptidase I activity, the levels of this enzyme within these cells was noted to vary greatly. Of special note, enzyme levels were highest in NK cells, monocytes (M-phi) and the cytotoxic T cell-enriched T8 cell subset. Furthermore, previously documented sensitivity to the toxic effects of Leu-Leu-OMe (second column, Table 10) was shown to be directly proportional to dipeptidyl peptidase I levels (third column, Table 10).
TABLE 10______________________________________CELLS WHICH ARE SENSITIVE TO THE TOXICEFFECTS OF LEU--LEU--OME HAVE A HIGHCONTENT OF THE LYSOSOMAL THIOL PROTEASE,DIPEPTIDYL PEPTIDASE I (CATHEPSIN C) Dipeptidyl Peptidase I Leu--Leu--OMe (nMole-beta Naphthyl/hr/Cell Type Sensitivity (LD.sub.50) micro-g protein)*______________________________________NK Cells 35 micro-M 2.54M-phi 75 micro-M 1.01T-8 Cells 250 micro-M 0.62B Cells >500 micro-M 0.13T4 Cells >500 micro-M 0.19Endothelial >500 micro-M 0.14CellsRenal Cell >500 micro-M 0.16Carcinoma______________________________________ *The enzyme was assayed in cellular protein at 37° C. with 1 micro dithiothreitol with 200 micromolar glycyl Lphenylalamyl-beta napthylamide
Dipeptidyl peptidase I is a lysosomal thiol peptidase which has been shown to remove amino terminal dipeptides from proteins. Alternatively, at neutral pH, incubation of this enzyme with high concentrations of dipeptide esters or amides has been shown to result in production of higher molecular weight polymerization products with the structure (R 1 -R 2 ) n --OR' (J. Biol. Chem. 1952; 195:645- 656). When R 1 and R 2 are amino acids with nonpolar side groups, such products are very hydrophobic and water insoluble (J. Biol. Chem. 1952; 195:645-656). As shown by the data displayed in Table 11, incubation of purified bovine dipeptidyl peptidase I (DPPI) at neutral pH with high concentrations of Leu-Leu-OMe results in production of a product which is insoluble in 10% TCA. Of note, much lower extracellular concentrations of Leu-Leu-OMe are required for production of a similar product within NK and T8 cells.
TABLE 11______________________________________LEU--LEU--OME IS METABOLIZED (POLYMERIZED)TO A TCA INSOLUBLE PRODUCT BY DIPEPTIDYLPEPTIDASE I (CATHEPSIN C) Fractional Conversion ofConcentration [.sup.3 H]Leu--Leu--OMe to a pro-of Leu--Leu--OMe duct which Precipitates in 10% TCA(micro-M) Intact NK, T8 Cells Purified DPPI______________________________________1 <0.1% <0.01%10 <0.2% 0.03%100 11.1% 0.08%250 23.2% ND1000 ND 20.0%______________________________________
Since such cells appear to take up and concentrate this compound by a facilitated transport mechanism (FIGS. 10 and 11), it is likely that intracellular concentrations of Leu-Leu-OMe comparable to those required for polymerization of this compound by purified DPPI are achieved. These results, therefore, suggest that the lo% TCA insoluble product of Leu-Leu-OMe produced by cytotoxic lymphocytes can be accounted for by the actions of DPPI present within these cells.
The following experiments were carried out to determine whether DPPI could generate a lytic product from Leu-Leu-OMe. In the experiment detailed in FIG. 12, 51 Cr-labeled human erythrocytes (RBC) were incubated with varying concentrations of Leu-Leu-OMe alone () or in the presence of purified bovine DPPI (). As shown by the results displayed in FIG. 12, exposure of RBC to either DPPI or Leu-Leu-OMe alone results in no damage to RBC. However, in the presence of higher concentrations of Leu-Leu-OMe and DPPI, RBC lysis occurs. That such damage to erythrocyte cell membranes is likely to be related to production of a higher molecular weight hydrophobic polymer of Leu-Leu-OMe is demonstrated by the results of the experiment detailed in Table 12.
TABLE 12______________________________________RED BLOOD CELL LYSIS CAN BE MEDIATED BYLEU--LEU--LEU--LEU--LEU--LEU--OMECompound Concentration of .sup.51 Cr ReleaseAdded Peptide Ester (micro-M) from RBC______________________________________Nil 0 410 ± 12LLOMe 2500 482 ± 121 500 482 ± 57 100 400 ± 27LLLLOMe 500 457 ± 41 100 425 ± 24LLLLLLOMe 500 3,531 ± 101 100 6,129 ± 400 20 698 ± 137______________________________________
Table 12 shows results of an experiment, where 51 Cr-labeled RBC's were incubated with varying concentrations of the methyl esters of the di-, tetra-, and hexa-peptides of leucine. Disruption of erythrocyte membranes was observed following exposure to the very hydrophobic compound (Leu) 6 -OMe.
As detailed in Table 13, the specific inhibitor of DPPI, Gly-Phe-CHN 2 blocks the toxic effects of Leu-Leu-OMe.
TABLE 13______________________________________A SPECIFIC INHIBITOR OF DIPEPTIDYL PEPTIDASEI PREVENTS LEU--LEU--OME MEDIATEDDEPLETION OF CD16(+) LYMPHOCYTES Cells stained withFirst Second alpha- alpha- alpha-Incubation Incubation CD16 CD4 CD8______________________________________Nil Nil 8.1 60.3 18.8Nil Leu--Leu--OMe <0.1 87.2 7.0Gly--Phe--CHN.sub.2 Nil 8.4 64.0 21.6Gly--Phe--CHN.sub.2 Leu--Leu--OMe 9.5 60.3 23.7______________________________________
Thus, as previously reported (see prior Examples and J. Immunol. 1986; 136:1038-1048), exposure of human PBL to 250 micro-M Leu-Leu-OMe results in loss of all CD16(+) NK cells, and the majority of CD8(+) T cells and thereby results in reciprocal enrichment of the CD4(+) T cell subset which is largely Leu-Leu-OMe resistant (see Table 13). However, when preincubated with 10 -6 M Gly-Phe-CHN 2 , PBL were resistant to these effects of Leu-Leu-OMe and the fraction of viable CD16(+) and CD8(+) lymphocytes did not significantly change after Leu-Leu-OMe exposure.
In the experiments detailed in FIG. 13A-13H, Cr-labeled RBC's were exposed to various dipeptide esters or amides in the presence () or absence of purified DPPI. The results indicate that DPPI is unable to produce a membrane active metabolite from D-Leu-D-Leu-OMe or from dipeptide esters containing at least one amino acid with a polar side group such as serine or tyrosine. The first observation is probably related to the inability of this enzyme to catalyze transpeptidation of peptide esters containing D-stereoisomers of amino acids. The latter observations are likely to be related to the fact that polymers of Ser-Leu or Leu-Tyr are not hydrophobic and therefore unlikely to enter and disrupt cell membranes.
All of the compounds analyzed in FIGS. 13A-13H with the exception of Leu-Leu-NH 2 are Leu-Leu-OBenzyl have previously been assessed for NK toxicity (see prior examples and PNAS 1985; 82:2468-24 72). In Table 14, results of experiments assessing the effects of these compounds on human NK function are detialed.
TABLE 14______________________________________INCUBATION OF MIXED LYMPHOCYTE POPULATIONSWITH LEUCYL-LEUCINE BENZYL ESTERRESULTS IN LOSS OF NK FUNCTION NK FunctionAddition During Preincubation % Specific Lysis K562______________________________________Nil 6612.50 micro-M Leu--Leu--OMe 6025.00 micro-M Leu--Leu--OMe 1250.00 micro-M Leu--Leu--OMe 2100.00 micro-M Leu--Leu--OMe <16.25 micro-M Leu--Leu--OBenzyl 6212.50 micro-M Leu--Leu--OBenzyl <125.00 micro-M Leu--Leu--OBenzyl 1250.00 micro-M Leu--Leu--NH.sub.2 711.00 milli-M Leu--Leu--NH.sub.2 66______________________________________
These results indicate that whereas Leu-Leu-NH 2 exhibits no discernible toxicity for NK Cells, exposure to relatively low concentrations of Leu-Leu-OBenzyl ablates human NK activity. Indeed, Leu-Leu-OBenzyl is greater than twofold more potent than Leu-Leu-OMe with respect to the capacity to deplete human PBL of cytotoxic lymphocytes.
Table 15 contains a summary of data detailed in Tables 5, 6 and 14, FIG. 13, and in previous Examples (also PNAS 1985; 82:2468-2472; J. Immunol. 1986; 136:6038-1048) and of additional experiments which demonstrated that Leu-OMe and Leu-Leu are not polymerized by DPPI to form a product capable of lysing RBS's.
TABLE 15__________________________________________________________________________FUNCTIONAL ACTIVITY OF VARIOUSAMINO ACID AND PEPTIDE DERIVATIVES Competitive Inhibition of Dipeptidyl Peptidase I .sup.3 H-Leu--Leu--OMe Catalyzed Lysis of ToxicityCompound Uptake Human RBC NK Cells__________________________________________________________________________Leu--Leu--OMe +++ +++ +++Leu--OMe - - -Leu--Leu ++ - -Leu--Leu--NH.sub.2 - +++ -Leu--Leu--OBenzyl ++++ +++++ +++++Val--Phe--OMe +++ ++ +++Leu--Phe--OMe +++ +++ +++Leu--Tyr--OMe ++++ - -Ser--Leu--OMe +++++ - -D-Leu--D-Leu--OMe - - -__________________________________________________________________________
The data summarized in Table 15 indicate that all compounds mediating NK toxicity in assays performed in this and prior examples share two characteristics:
1. Such NK toxic reagents competitively inhibit [ 3 H]Leu-Leu-OMe uptake by human PBL and are therefore likely to be concentrated within lymphocytes by the same facilitated transport mechanism.
2. All NK toxic compounds are composed of amino acids with non-polar side groups and are suitable substrates for a DPPI catalyzed polymerization reaction which produces a hydrophobic product that disrupts erythrocyte cell membranes.
These studies, therefore, indicate that all dipeptide esters or amides with these characteristics (including Leu-Leu-OBenzyl, see Table 14) are likely to have the same immunosuppressive activities as the dipeptide alkyl esters reported earlier herein. Furthermore, these studies are the first to demonstrate that dipeptidyl peptidase I levels are selectively increased in cytotoxic lymphocytes. It can therefore be hypothesized that inhibition of this enzyme with Gly-Phe-CHN 2 or similar selective dipeptidyl peptidase I inhibitors should alter the function of these cells and therefore may act as an immunosuppressive agent of value in therapy of the same diseases or conditions as proposed for Leu-Leu-OMe or similar agents (albeit by a different mechanism).
Example 14
NK Toxicity of Peptide Amides
These experiments were designed to assess the NK toxicity of dipeptide amides. In previous studies (see prior Examples and PNAS 82:2468-2472), the present inventors demonstrated that NK toxic effects of Leu-Leu-OMe were only seen when lymphocytes are exposed for 15 minutes at room temperature to Leu-Leu-OMe concentrations in excess of 12.5 micro-M. Whereas Leu-Leu-OBenzyl is a more potent NK toxin than is Leu-Leu-OMe, Leu-Leu-NH 2 has no demonstrable NK toxic effects (see Tables 14 and 15 of Example 13). The experiment detailed in Table 16 demonstrated that whereas Gly-Phe-OMe is a much less potent NK toxin than is Leu-Leu-OMe; and Gly-Phe-NH 2 , like Leu-Leu-NH 2 , has no apparent NK toxic effects; glycylphenylalanine-beta-naphthylamide is a very potent NK toxin.
TABLE 16______________________________________INCUBATION OF MIXED LYMPHOCYTE POPULATIONSWITH GLYCYL-PHENYLALANINE-BETA-NAPHTHYL-AMIDE RESULTS IN LOSS OF NK FUNCTION NK Function % SpecificAddition During Preincubation Lysis K562______________________________________Nil 40.850 micro-M Leu--Leu--OMe 1.1250 micro-M Gly--Phe--OMe 34.5500 micro-M Gly--Phe--OMe 10.1250 micro-M Gly--Phe--NH.sub.2 43.91 micro-M Gly--Phe--beta-Naphthylamide 52.55 micro-M Gly--Phe--beta-Naphthylamide 1.220 micro-M Gly--Phe--beta-Naphthylamide 0.6______________________________________
Additional studies demonstrated that Gly-Phe-beta-naphthylamide competitively inhibits [ 3 H]Leu-Leu-OMe uptake by lymphocytes, whereas simple amide derivatives of Leu-Leu-OMe do not compete for uptake by this facilitated transport mechanism (see Table 15, Example 13).
On the basis of these findings and those contained in Table 14, Example 13, ester or amide derivatives of Leu-Leu or similar dipeptides which contain benzyl, naphthylamine or similar non-polar ring structures should prove to be selectively toxic for cytotoxic lymphocytes at lower concentrations than Leu-Leu-OMe and thus have enhanced clinical efficacy.
In addition, because the peptide bond between the first and second amino acid in Leu-Leu-CMe need not be cleaved in the mediation of NK toxicity, alterations of the peptide bond as detailed in FIGS. 14A and 14B, (i.e. a thiopeptide analog of Leu-Leu-OMe (FIG. 14A) or the use of peptides such as leucyl-N-methyl leucine-methyl ester (FIG. 14B)) may serve to produce an NK-toxic drug of equal or better concentration-dependent activity. As aminopeptidases capable of degrading Leu-Leu-OMe by cleavage of this peptide bond are less likely to degrade such compounds, they are more apt to have a longer in vivo half-life and therefore enhanced efficacy.
Modifications of amino acid R groups which preserve the non-polar nature of the amino acid R groups in dipeptide esters such as Leu-Leu-OMe and the activity of this compound as a substrate for dipeptidyl peptidase I should result in therapeutic agents with enhanced efficacy, since not all peptidases capable of degrading Leu-Leu-OMe may be able to degrade dipeptide esters containing non-physiologic side chains. Examples of some non-physiological dipeptide esters are detailed in FIGS. 15A-15C, where, for simplicity, they are shown as dipeptide methyl esters only.
Example 15
Prevention of Graft Versus Host Disease
Graft vs. host disease (GVHD) remains one of the major problems preventing an expanded use of human bone marrow transplantation (1,2). Although it is theoretically possible to avoid GVHD by careful histocompatibility matching, it is not currently feasible to match donor and recipient routinely for all major histocompatibility antigens. Moreover, there are no in vitro tests to detect minor antigenic disparities that can also stimulate GVHD (3). Because numerous studies in laboratory animals have shown that removal of immunocompetent T lymphocytes from the donor inoculum will prevent GVHD (4,5), the approaches to obviate GVHD in man have also focused on deleting T cells from the donor marrow. The available methodology for human T cell depletion, however, has not proven unifirmly effective in preventing GVHD (6-9).
The present Example shows a new approach to the prevention of GVHD. Using a murine model of bone marrow transplantation, the effects of treating donor inoculum with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe), a compound that eliminates cells with cytotoxic potential (10) was studied. Leu-Leu-OMe is toxic to human natural killer cells (NK), activated cytotoxic T cells (CTL), precursors of CTL (pre-CTL), and monocytes (see 11 and earlier Examples herein). Of importance, both CD8-positive and CD4-positive precursors ant effectors of CTL are removed from mixed cell populations by Leu-Leu-OMe. By contrast, helper T cells, B cells, and a variety of nonhemopoietic cells are unaffected (see earlier Examples and 10, 11). Murine NK and pre-CTL were found to be very similar to human cells in concentration-dependent sensitivity to Leu-Leu-OMe (see earlier Examples and 12). To determine whether Leu-Leu-OMe might affect the induction of, or alter the pattern of tissue injury in GVHD, a murine model of bone marrow transplantation was used that is skewed toward GVHD in that it crosses major histocompatibility barriers and uses a several fold excess of donor T cells. The experimental results predicted in earlier Examples and described here indicate that Leu-Leu-OMe treatment of the donor inoculum had the capacity to prevent lethal GVHD with no apparent toxic effects on stem cell function.
The methods used in this Example are described as follows:
Mice
Female, 8-16-week-old, C57BL/6J (B6) and (C57BL/6J x DBA/2J)Fl mice (B6D2Fl) were used as donors and recipients, respectively. For some experiments B6 donors were immunized by injecting 70×10 6 cells/ml either in phosphate-buffered saline (PBS) or in Leu-Leu-OMe dissolved in PBS. Leu-Leu-OMe was synthesized from leucyl-leucine as previously described (10). After a 15 min incubation at room temperature, the cells were washed once, suspended in Hanks' balanced salt solution, counted, and infused via a lateral tail vein into irradiated (950 cGy) Fl recipients.
Immediately after treatment with Leu-Leu-OMe, there was less than a 5% loss of viable donor cells. Following a 3-h incubation at 37° C., however, the number of Lyt-2 + spleen cells was decreased by more than 65%, whereas there was no alteration in the number of L3T4 + cells (see earlier Examples and 12).
Survival studies
Survival times were measured from the day of transplantation to the day of death. Deaths occurring within 8 d of transplantation were considered to be the result of radiation-induced gastroenteritis and were excluded. The nonparametric Mann-Whitney test was used to determine whether the median survival times (MST) differed between groups (14).
Assessment of spleen cell H-2 phenotype
Spleen cells from control mice (normal B6 or B6D2F 1 ) and long-term BMTx survivors (B6→B6D2Fl) were depleted of B cells by panning on goat anti-mouse immunoglobulin-coated petri dishes (15). Aliquots of B cell-depleted spleen cells were incubated either with antibody 30-5-7.S (anti-L d [16]), antibody 28-18-3.S (anti-k b [17]), or with a relevant isotype control antibody for 30 min at 4° C. Cells were then washed and incubated with a fluorescein isothiocyanate-labeled goat anti-mouse immunoglobulin (GAMIG-FITC, Cappell Laboratories, Cochranville, Pa.) and analyzed on a flow cytometer (Ortho system 50 HH, Ortho Diagnostics, Raritan, NJ).
Measurement of stem cell function
Bone marrow cells or marrow and spleen cell mixtures were incubated in PBS with or without 250 micro-M Leu-Leu-OMe as above and then infused into 950 cGy irradiated syngeneic recipients. 5 d later, splenic 5-iodo-2'-deoxyuridine- 125 I ( 125 I-UdR) uptake was measured as previously described (15).
Histology
Organs of recipient mice were fixed in 10% buffered formalin. Sections were stained with Hematoxylin and Eosin.
The results of this study are as follows:
Survival of transplanted mice
To assess the effects of Leu-Leu-OMe treatment of the donor inoculum on lethal GVHD, B6 donor cells were incubated with varying concentrations of Leu-Leu-OMe before infusing them into irradiated B6D2FI recipients. As shown in FIG. 16A, the recipients of 25×10 6 untreated donor cells died rapidly. Recipients given 25× 10 6 cells preincubated with 125 micro-M Leu-Leu-OMe had significantly delayed mortality from GVHD (median survival time of 41.5 vs. 19 d, P<0.001), but all eventually died. By contrast, recipients of donor cells treated with 250 micro-M Leu-Leu-OMe all survived. Similar results were obtained in four separate experiments using 25×10 6 donor cells treated with 250 micro-M Leu-Leu-OMe. When the donor inoculum was doubled to 50×10 6 cells (FIG. 16B), all of the recipients of donor inocula treated with 250 micro-M Leu-Leu-OMe survived. Even when immune donors were used and the control mice experienced accelerated GVHD (FIG. 17), the recipients of donor cells treated with 250 micro-M Leu-Leu-OMe manifested significantly prolonged survival (median survival times of 49 vs. 11 d, P<0.001) and three of nine became long-term survivors.
GVHD-mediated tissue injury
Control mice from all three experimental conditions exhibited acute cutaneous GVHD within 2 wk of transplantation, manifested clinically by alopecia and scaling, and histologically by epidermal basal layer liquefaction, epidermal lymphocytic infiltration, and a mononuclear cell infiltrate in the dermis. The recipients of 25×10 6 donor cells treated with 125 micro-M Leu-Leu-OMe also manifested evidence of acute GVHD, although at somewhat diminished intensity, whereas the recipients of 25×10 6 cells treated with 250 micro-M Leu-Leu-OMe had no evidence of cutaneous GVHD by inspection or biopsy early after transplantation and no evidence of GVHD in any target organs at the time of sacrifice, 125 d after bone marrow transplantation. By contrast, all five recipients of 50×10 6 Leu-Leu-OMe treated cells manifested acute cutaneous GVHD. Two of five developed a progressive widespread dermal sclerosis beginning 3 wk after transplantation. This was most severe 3 mo after transplantation and then substantially resolved. At the time of sacrifice (275 d after bone marrow transplantation) these two mice had only mild residual dermal sclerosis, and a mild to moderate periportal round cell infiltrate in the liver.
Demonstration of stable chimerism in mice transplanted with Leu-Leu-OMe treated cells
To see whether the donor hemopoietic system remained dominant over that of the irradiated recipient, we characterized the H-2 phenotype of spleen cells from the mice used in the survival experiments at various times after transplantation. Spleen cells from normal B6 (donor, H-2 b ) and B 6D2F 1 (recipient, H-2 b /H-2 d ) mice served as controls. Cells from three separate experimental groups analyzed as long as 275 d after transplantation consistently displayed the phenotype and staining pattern of the homozygous donor and not the H-2 heterozygous Fl recipient (>95% reactivity with anti-H-2 b , <1% reactivity with anti-H-2 d ).
Lack of stem cell toxicity
To assay the effects of Leu-Leu-OMe on hemopoietic stem cells, we incubated marrow or mixtures of marrow and spleen cells in PBS with or without Leu-Leu-OMe and measured splenic 125I-UdR uptake 5 d after transplantation into irradiated syngeneic recipients (18). Data in Table I indicate that treatment with 250 micro-M Leu-Leu-OMe had no deleterious effect on this measure of stem cell function. Since human marrow obtained for use in transplantation has variable amounts of peripheral blood contamination, we also studied the stem cell function of a mixture of murine spleen and marrow incubated with Leu-Leu-OMe. Again there was no decrement in 125 I-UdR uptake, suggesting that "bystander" stem cells are not damaged when the numerous cytotoxic cells are lysed by Leu-Leu-Ome. Histologic examination of spleens 5 d after irradiation revealed the expected hypocellularity in the nontransplanted control group and equivalent erythrocytic, granulocytic, and megakaryocytic regeneration in the spleens of recipients of treated or nontreated marrow cells. Histological studies were conducted of spleens from irradiated mice. B6 mice were irradiated with 950 cGy and given no marrow (irradiation control), or given syngeneic bone marrow cells that had been incubated in PBS with or without 250 micro-M Leu-Leu-OMe. 5 d later spleens were examined histologically. Irradiation control spleens were sparsely populated, with no hemopoietic elements. Recipients of marrow treated with 250 micro-M Leu-Leu-OMe had the vast majority of their splenic red pulp packed with erythroblasts, but also had numerous peritrabecular areas containing megakaryocytes and granulocytic elements. A high power view, of a recipient of marrow treated with 250 micro-M Leu-Leu-OMe (x200) and of a recipient of control marrow (x200) showed that the patterns of repopulation of these spleens were identical in megakaryocytes and granulocytes.
This study indicates that Leu-Leu-OMe treatment of donor cells is able to prevent lethal GVHD across major histocompatibility barriers in this strain combination with no detectable stem cell toxicity. Since especially severe GVHD occurs when immune donors are used, it is noteworthy that one 15-min incubation of primed donor cells with 250 micro-M Leu-Leu-OMe nevertheless significantly increased survival (FIG. 17).
Spleen cells from surviving mice, assessed as long as 275 d after transplantation, consistently displayed the donor H-2 type, demonstrating that stable chimerism had been established. In addition, the absolute numbers of B cells, L3T4 + and Lyt2 + T cells, and NK function in the spleens of long-term B6>B6D2Fl chimeras were equivalent to that of age-matched animals transplanted with syngeneic bone marrow and spleen cells (B6→B6) (data not shown). Moreover, functional assessment of spleen cells from B6>B6D2FI chimeras indicated that the immune system of these animals had regained the capacity to proliferate and to generate cytotoxic T cells to third-party stimulators (H-2 k ), but remained unresponsive to host alloantigens.
The mechanism whereby Leu-Leu-OMe prevents GVHD appears to be distinct from that of other regimens. The administration of anti-asialo GM 1 in vivo prevents lethal GVHD across minor histocompatibility barriers (19) but not across major-histocompatability barriers with the same dosage schedule. Using monoclonal antibodies to cell surface antigens, Korngold and Sprent (20) have recently shown that lethal GVHD resulting from a full H-2 mismatch can only be eliminated by removal of T cells with a pan-T cell reagent, and not with antibodies to either L3T4 or Lyt-2 alone. The incubation of human cells in vitro with 250 micro-M Leu-Leu-OMe selectively depletes those with cytotoxic potential regardless of phenotype (11); murine lymphocytes are similarly affected (12). Indeed, the concentration-dependent capacity of Leu-Leu-OMe to eliminate murine splenic cytotoxic T cells closely parallels its efficacy in reducing the severity of GVHD. The incubation of B6 spleen cells with 100 micro-M Leu-Leu-OMe results in complete loss of NK function but only partial reduction of the generation of allospecific cytotoxic T cells (see prior Examples and 12). As predictable from the results above, incubation of B6 spleen and marrow cells with 125 micro-M Leu-Leu-OMe delayed, but did not eliminate death from GVHD (FIG. 16A). Treatment of cells with 250 micro-M Leu-Leu-OMe caused near total ablation of allocytotoxicity (12) and prevented lethal GVHD (FIG. 16, A and B). The results support the hypothesis that the depletion of cytotoxic T cell precursors from the donor inoculum and the resultant absence of cytotoxicity during the interval between transplantation and hemopoietic reconstitution may have facilitated the development of stable chimerism in this strain combination. Alternatively, it may be that other unrecognized functions of these same Leu-Leu-OMe sensitive cells are important in the development of GVHD.
The histology of the long-term survivors revealed no evidence of GVHD in any target organ in recipients of 25 million treated cells 125 d after transplantation. The mild residual dermal sclerosis 275 d after transplantation in two of five mice receiving 50 million treated cells was not accompanied by epidermal, dermal, or follicular lymphocytic infiltration, and therefore appeared to be an inactive process. A periportal round cell infiltrate was observed in the livers of all five of these mice, however, suggesting that they developed a mild, nonscarring form of chronic hepatic GVHD. It appeared that the few cells with cytotoxic potential that remain after a single treatment with 250 micro-M Leu-Leu-OMe (<5%) (see prior Examples and 12) were insufficient in the 25×10 6 incculum to cause any GVHD, but were sufficient in the 50×10 6 inoculum to cause the self-limited cutaneous GVHD and the mild chronic hepatic GVHD. However, the possibility remains that a Leu-Leu-OMe-resistant, noncytotoxic cell of low frequency in the donor inoculum caused the limited GVHD seen in the recipients of 50×10 6 B6 cells and the more severe GVHD s®en in the recipients of immune B6 cells. Studies using other models of murine GVHD have suggested a role for helper T cells in causing a periportal lymphocytic infiltrate in the liver (21) and dermal sclerosis (22). These hypotheses are not mutually exclusive. It should be noted, however, that in the current studies even these nonlethal manifestations of GVHD were only observed when very large numbers of donor Leu-Leu-OMe treated donor cells were used.
The present studies clearly demonstrate the selective nature of the effects of Leu-Leu-OMe. Leu-Leu-OMe had no discernible toxicity for marrow stem cells, yet prevented GVHD. Erythroid regeneration, as assessed by splenic 125 I-UdR uptake, was not diminished (Table 17) and newly generated granulocytic, erythrocytic and megakaryocytic elements were observed histologically following treatment with Leu-Leu-OMe. In contrast to current regimens used in human bone marrow transplantation, Leu-Leu-OMe treatment of donor marrow is a relatively rapid and simple technique. Because Leu-Leu-OMe appears to delete certain cells based on their functional capabilities, rather than on their cell surface markers, it may offer a new approach to avoid GVHD in humans.
TABLE 17______________________________________In Vivo Proliferation of Hemopoietic Stem Cells Splenic .sup.125 I-UdR uptake (96)Experi- Cells Treatment of geometric meanment.sup.1 n.sup.2 grafted cells (95% CL).sup.3______________________________________1 8 3 × 10.sup.6 Vehicle 0.87 (0.70-1.09) 8 3 × 10.sup.6 Leu--Leu--OMe 0.99 (0.78-1.28) 5 0 0.012 11 3 × 10.sup.6 Vehicle 0.48 (0.31-0.78) 11 3 × 10.sup.6 Leu--Leu--OMe 0.45 (0.30-0.67) 6 0 0.013 6 3 × 10.sup.6 Vehicle 2.72 (2.29-3.21) 7 3 × 10.sup.6 Leu--Leu--OMe 3.02 (2.32-3.91)4 8 4 × 10.sup.6 Vehicle 1.06 (0.78-1.47) 6 4 × 10.sup.6 Leu--Leu--OMe 0.83 (0.46-1.50)5 6 2.5 × 10.sup.6 Vehicle 1.28 (0.68-2.39) 6 2.5 × 10.sup.6 Leu--Leu--OMe 1.37 (1.10-1.46)______________________________________ .sup.1 Marrow alone (experiments 1-3), or a mixture of spleen and marrow at a 4:1 ratio (experiments 4 and 5), were incubated either in PBS alone or in 250 microM Leu--Leu--OMe before being transferred into irradiated syngeneic recipients. .sup.2 Mice per group. .sup.3 CL, confidence limits).
References for Example 15
1. Gale, R. P. 1985. Graft-versus-host disease, Immunol. Rev. 88:193-214.
2. Storb, R., and E. D. thomas. 1985. Graft-vs-host disease in dog and man: the Seattle Experience, Immunol. Rev. 88:215-238.
3. Tsoi, M. S., R. P. Warren, R. Storb, R. P. Witherspoon, E. Michelson, E. R. Giblett, M. S. Schanfield, P. Weiden, and E. Thomas. 1983. Autologous marrow recovery and sensitization to non-HLA antigens after HLA-identical marrow transplantation for aplastic anemia. Exp. Hematol. 11:73.
4. Korngold, R., and J. Sprent. 1978. Lethal graft-versus-host disease after one marrow transplantation across minor histocompatibility barriers in mice. J. Exp. Med. 148:1687-1698.
5. Vallera, D. A., C. C. B. Soderling, G. J. Carlson, and J. H. Kersey. 1981. Bone marrow transplantation across major histocompatibility barriers in mice. III. Treatment of donor grafts with monoclonal antibodies directed against Lyt determinants. J. Immmunol. 128:871- 875.
6. Hayward, A. R., S. Murphy, J. Githens, G. Troup, and D. Ambruso. 1982. Failure of a pan-reactive anti-T cell antibody, OKT 3, to prevent graft versus host disease in severe combined immunodeficiency. J. Pediatr. 100:665- 668.
7. Vogelsang, G. B., A. D. Hess, A. W. Berkman, P. J. Tutschka, E. R. Farmer, P. J. Converse, and G. W. Santos. 1985. An in vitro predictive test for graft versus host disease in patients with genotypic HLA-identical bone marrow transplants. N. Engl. J. Med. 313:645-650.
8. Beatty, P. G., R. A. Clift, E. M. Mickelson, B. B. Nisperos, N. Flournoy, P. J. Martin, J. E. Sanders, P. Stewart, C. D. Buckner, R. Storb, E. D. Thomas, and J. A. Hansen. 1985. Marrow transplantation from related donors other than HLA-identical siblings. N. Ergl. J. Med. 313:765-771.
9. Goldman, J. M., J. F. Apperley, L. Jones, R. Marcus, A. W. G. Goolden, R. Batchelor, G. Hale, H. Waldmann, C. D. Reid, J. Hows, E. Gordon-Smith, D. Catovsky, and D. A. G. Galton. 1986. Bone marrow transplantation for patients with chronic myeloid leukemia. N. Engl. J. Med. 314:202-207.
10. Thiele, D. L., and P. E. Lipsky. 1985. Regulation of cellular function by products of lysosomal enzyme activity: elimination of human natural killer cells by a dipeptide methyl ester generated from L-Leucine methyl ester by monocytes or polymorphonuclear leukocytes. Proc. Natl. Acad. Sci. USA. 82:2468-2472.
11. Thiele, D. L., and P. E. Lipsky. 1986. The immunosuppressive activity of L-leucyl-L-leucine methyl ester: Selective ablation of cytotoxic lymphocytes and monocytes. J. Immunol. 136:1038-1048.
12. Thiele, D., M. Charley, J. Calomeni, and P. Lipsky. 1986. Selective depletion of cytotoxic cells with L-leucyl-L-leucine methyl ester prevents lethal graft-vs-host disease after transplantation of histo-incompatible bone marrow and spleen. Clin. Res. 34:673a. (Abstr.)
13. Charley, M. R., J. L. Bangert, B. L. Hamilton, J. N. Gilliam, and R. D. Sontheimer. Murine graft-versus-host skin disease: a chronological and quantatative analysis of two histologic patterns. J. Invest. Dermatol. 81:412- 417.
14. Mann, H. B., and D. B. Whitney. 1947. On a test of whether one or two random variables is stochastically larger than the other. Annals of Mathematics and Statistics. 18:50-60.
15. Wysocki, L. J., and V. L. Sato. 1978. Panning for lymphocytes: A method for cell selection. Proc. Natl. Acad. Sci. USA. 75:2844.
16. Ozato, K., T. H. Hansen, and D. H. Sachs. 1980. Monoclonal antibodies to mouse MHC antigens. II. Antibodies to the H-2L d antigen, the products of a third polymorphic locus of the mouse major histocompatibility complex. J. Immunol. 125:2473.
17. Ozato, K., and D. A. Sachs. 1981. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2 d haplotype reveal genetic control of isotype expression. J. Immunol. 126:317.
18. Bennett, M., G. Cudkowicz, R. S. Foster, Jr., and D. Metcalf. 1986. Hemopoietic progenitor cells of W anemic mice studied in vivo and in vitro. J. Cell. Physiol. 71:211-226.
19. Charley, M. R., a. Mikhael, M. Bennett, J. N. Gilliam, and R. D. Sontheimer. 1983. Prevention of lethal minor-determinate, graft-versus-host disease in mice by the in vivo administration of anti-asialo GM 1 . J. Immunol. 131:2101-2103.
20. Korngold, R., and J. Sprent. 1985. Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences. J. Immunol 135:3004-3010.
21. Van Rappard-Van Der Veen, Feikje M., T. Radaszkiewicz, L. Terraneo, and E. Gleichmann. 1983. Attempts at standardization of lupus-like graft-vs-host disease: inadvertent repopulation by DBA 2 spleen cells of H-2-different nonirradiated Fl mice. J. Immunol. 130:2693-2701.
22. DeClerk, Y., V. Draper, and R. Parkman. 1986. Clonal analysis of murine graft-vs-host disease. II. Leukokines that stimulate fibroblast proliferation and collagen synthesis in graft-vs. host disease. J. Immunol. 36:3549-3552.
The various published literature articles cited in this application are incorporated in pertinent part by reference herein for the reason cited.
Changes may be made in the construction, operation and arrangement of the various elements, steps and procedures described herein without departing from the concept and scope of the invention as defined in the following claims.
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Esters or amides of a peptide, preferebly a dipeptide, consisting essentially of natural or synthetic L-amino acids with hydrophobic side chains were found to have specific cellular toxicities. Preferable amino acids of the peptide are leucine, phenylalanine valine, isoleucine, alanine, proline, glycine or aspartic acid beta methyl ester. Preferable dipeptides are L leucyl L-leucine, L-leucyl L-phenylalanine, L-valyl L-phenylalanine, L-Leucyl L-isoleucine, L-henylalanyl L-phenylalanine, L-valyl L-leucine, L-leucyl L-alanine, L-valyl L-valine, L-phenylalanyl L leucine, L prolyl L-leucine, L-leucyl L-valine, L-phenylalanyl L-valine, L glycyl L-leucine, L-leucyl L-glycine, glycyl L-phenylalanine and L-aspartyl beta methyl ester L-phenylalanine. Most preferable dipeptides are L-leucyl L-leucine, L-leucyl L-phenylalanine, L-valyl L-phenylalanine, L-phenylalanyl L-leucine, L-leucyl L-isoleucine L-phenylalanyl L-phenylalanine and L-valyl L-leucine.
The ester or amide of the dipeptide is most preferably alkyl, aralkyl or aryl a preferred alkylester is a methyl ester and may also be an ethyl ester or alkyl of up to about four carbon atoms such as propyl, isopropyl, butyl or isobutyl. Yet larger alkyl substituents may also be functional judging from the beta naphthyl substituent which is functional in certain embodiments.
These alkyl, aryl or arylkyl esters and amides of dipeptides consist essentially of amino acids with hydrophobic side chains may be used to deplete cytotoxic T-lymphocytes or natural killer cells from organisms, cell populations or tissues.
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BACKGROUND OF THE INVENTION
1. Field of Invention
The present invention pertains to the field of mechanical technology. The invention relates to an abrasive belt polishing finisher.
2. Related Art
The polishing finisher is a device particularly designed for finishing the surface of metallic products including steel, aluminum or copper or pipes. By using the polishing finisher, snow patters, drawing patterns, wave patterns, matter surfaces and mirror surfaces of different precisions could be produced, and deep scratches and slight scratches can be quickly repaired. The polishing finisher could be used for deburring and rounding and processing decorative metals, which will not result in any shadow, transition areas or uneven decorative surfaces during processing. As such, the polishing finisher is an important device for production of metallic products.
The abrasive belt polishing finisher grinds the surface of a work piece by means of the driving abrasive belt, which achieves flexible grinding and provides grinding, polishing and finishing effects. Compared with the polishing finishers in which the polishing and finishing treatment could be directly conducted by the finishing wheels, the abrasive belt polishing finisher is safer for processing and generates less noise and dust. The surface of the work piece has a higher quality after processing and a wider scope of application.
However, the conventional work pieces generally have several curved surfaces to be finished, and each of the curved surfaces has a curvature different from each other. When the conventional abrasive belt polishing finishers are used to finish the work pieces, finishing could not be efficiently carried out by using the flat abrasive belt. If other finishing wheels have to be removed or replaced, not only is the operation inconvenient, but also the finishing efficiency is low.
SUMMARY OF THE INVENTION
In order to address the problems existing in the prior art, it is an object of the invention to provide an abrasive belt polishing finisher which could perform continuous polishing treatment for a number of different curved surfaces.
The present invention provides an abrasive belt polishing finisher, comprising a finishing wheel transform mechanism. The transform mechanism includes a motor and a connection support. The central section of the connection support is fixedly connected with the output shaft of the motor. Several self-rotable support finishing wheels are provided around the connection support. The curve surface of the rim of each of the support finishing wheels has a different curvature. Each support finishing wheel is distributed on the same circle centered on the output shaft of the motor. The connection support is driven by the motor into rotation to press and position one of the support finishing wheels against the back of the abrasive belt in the polishing finisher.
When the finishing wheel transform mechanism of the abrasive belt polishing finisher is in use, it is fixed on the back of the abrasive belt in the polishing finisher. The operator could control the driving device of the polishing finisher to bring the abrasive belt into transmission. When curved surfaces of different curvatures on the work piece to be processed are to be polished, the motor is driven to work to bring the connection support and the support finishing wheels connected round the connection support into rotation about the output shaft thereof. When the support finishing wheel of the corresponding curvature rotates to the back of the abrasive belt to be positioned, the outer circumference of the support finishing wheel is beyond the original position of the abrasive belt, and the abrasive belt is pressed against the rim of the support finishing wheel to form a curved surface of a curvature the same as that of the rim of the support finishing wheel on the front surfaces thereof. The work piece to be processed is located here to finish the curved surface of the corresponding curvature. In the process of finishing, the support finishing wheel rotates around its own rotation axis, which could reduce the abrasion caused by the friction between the abrasive belt and the rim of the support finishing wheel. If curved surfaces of different curvatures have to be finished, the motor could be driven again to bring the support finishing wheel of the corresponding curvature to the back of the abrasive belt.
In the abrasive belt polishing finisher, the support finishing wheel comprises a wheel-like body and an annular finishing cover covered outside of the body, the back of the finishing cover is fixedly connected with the body, and a finishing curved surface is provided on the outer side thereof against the back of the abrasive belt.
In the abrasive belt polishing finisher, the finishing cover is made from rubber materials.
According to the first aspect of the connection support, in the abrasive belt polishing finisher, the connection support comprises a connection part fixedly connected with the outer end of the output shaft of the motor and several rod-like support parts disposed in the radial direction of the output shaft of the motor. The number of the support parts is the same as that of the support finishing wheels. The outer ends of the support parts are respectively connected with the support finishing wheels.
In the abrasive belt polishing finisher, the support parts are evenly distributed around the output shaft of the motor. The axis of the support finishing wheel is identical to that of the output shaft of the motor. The support finishing wheels are fixedly connected with the outer ends of the support parts through connection pieces opened along the axis of the support finishing wheels. The connection piece is a screw.
In the abrasive belt polishing finisher, the said finishing wheel transform mechanism further includes a controller and a detection module connected with the controller. The detection module is provided at the motor and the connection support and could detect that a stop signal is sent to the controller when the support finishing wheels along with the connection support rotate to the back of the abrasive belt. The controller could control the motor to stop working and be positioned after receiving the stop signal from the detection module. The detection module detects whether the support finishing wheel has turned to a set position, and the motor is automatically controlled by the controller, which provides a convenient operation and high control precision.
In the abrasive belt polishing finisher, the detection module includes a proximity switch and sensor blocks in the same number as the support finishing wheels disposed outside of the motor. Each of the sensor blocks is correspondingly fixedly connected with the support post connected with the support finishing wheel and could move to a position opposite to the proximity switch when it rotates to the back of the abrasive belt along with the support finishing wheel. The proximity switch is disposed outside of the motor and will not move. One side of the proximity switch which could detect the object faces to the back of the abrasive belt, and the proximity switch could detect the object is approaching and send the stop signal to the controller when the sensor block moves to a corresponding position.
In the other case, in the abrasive belt polishing finisher, the detection modules includes infrared receiving units fixedly connected with the outer side of the motor and infrared emitting units in the same number as that of the support finishing wheels. The infrared emitting units are corresponding to the support parts respectively and move to the positions corresponding to the infrared receiving units when they rotate to the back of the abrasive belt along with the support finishing wheels.
According to the first positioning mode of the connection support, in the abrasive belt polishing finisher, the motor is a brake motor. An electro-magnetic brake is located at the tail of the brake motor. When the motor is powered on, the electro-magnetic brake will be powered on and pulled in, and the motor will not be braked. When the motor is powered off, the electro-magnetic brake is powered off as well. The motor is braked by the brake under the action of the spring, so that the output shaft thereof will not rotate any more and be positioned.
According to the second positioning mode of the connection support, in the abrasive belt polishing finisher, the transform mechanism further includes a solenoid valve on the connection support and several via holes opened on the connection support. The coils of the solenoid valve are connected to the supper supply loop of the motor. When the said support finishing wheels rotate to the back of the abrasive belt, the power supply loop stops supplying power to the motor and starts to supply power to the solenoid valve, to extend the outer end of the solenoid valve into one of several via holes.
A large amount of space of the area surrounded by the abrasive belt will be occupied when the connection support is located in the area surrounded by the finisher abrasive belt. In other words, relatively more space outside of the finisher will be occupied by the connection support and the support finishing wheels. The angle and position of the manipulator for holding the work piece have to change at times to ensure uniform polishing on the work piece in the process of polishing and finishing. As such, when the manipulator is located at the finisher adjacent to the back of the abrasive belt, it tends to collide with the connection support and the support finishing wheels, which impairs the reliability of polishing and finishing of the work piece.
In order to address the aforesaid problem, as an improvement, in the abrasive belt polishing finisher, the abrasive belt polishing finisher further comprises a frame, a driving wheel and a driven wheel provided on the frame, and an abrasive belt covered on the driving wheel and the driven wheel. A driving mechanism connected with the finishing wheel transform mechanism is further provided on the frame. The connection support in the finishing wheel transform mechanism could move between a first position and a second position along the axis of the support finishing wheels. In the first position, the driving mechanism drives the connection support in movement to disengage the support finishing wheels from the abrasive belt and locate the support finishing wheels out of an area surrounded by the abrasive belt. In the second position, the driving mechanism drives the connection support to move into the area surrounded by the abrasive belt and makes the support finishing wheels right toward the back of the abrasive belt, and the support finishing wheels could be in contact with the abrasive belt driven by the finishing wheel transform mechanism.
The driving wheel drives the abrasive belt into rotation to grind the surface of the work piece in contact with the abrasive belt. When a curved surface is to be polished on the surface of the work piece, the connection support could be driven by the driving mechanism to move to the second position along the axis of the support finishing wheel thereon, and a support finishing wheel on the connection support is selected according to the curvature of the curved surface required by the surface of the work piece. A shape identical to the rim of the selected support finishing wheel is formed on the surface of the abrasive belt. As a result, the curved surface could be polished when the work piece is in contact with the surface of the abrasive belt.
When the support finishing wheel on the connection support does not have to be used, the connection support could move reservedly to the first position merely controlling the driving mechanism. The connection support is away from the back of the abrasive belt and returns to its initial position. As the connection support could move along the axis of the support finishing wheel by using the driving mechanism, the connection support is away from the back of the abrasive belt when it does not have to used, and space on the back of the abrasive belt on the frame could be completely left. Such a structure could largely save the space and facilitate operation of the manipulator, for which the work piece could be better polished.
In the abrasive belt polishing finisher, connection rod finishing wheels movable between the polishing position and the reset position are further provided in the area surrounded by the abrasive belt. In the polishing position, the connection support moves to the first position to disengage the support finishing wheels from the abrasive belt and locate the support finishing wheels out of the area surrounded by the abrasive belt, and the connection rod finishing wheels move to the back of the abrasive belt and contact with the abrasive belt. In the reset position, the connection rod finishing wheels disengage from the back of the abrasive belt to return to the area surrounded by the abrasive belt.
In the abrasive belt polishing finisher, the connection rod finishing wheels are respectively located above and under the connection support, and the position of the connection rod finishing wheels in contact with the abrasive belt after moving is identical to that of the support finishing wheels in contact with the abrasive belt after the connection support moves.
Particularly, in the abrasive belt polishing finisher, a first connection rod and a first driving cylinder are provided on the frame. The first connection rod and the first driving cylinder are located above the connection support and out of the area surrounded by the abrasive belt. One end of the first connection rod is hinged to the frame and the other end thereof is connected with the connection rod finishing wheel within the area surrounded by the abrasive bet. The end of the piston rod of the first driving cylinder is hinged to the first connection rod and the end of the cylinder body of the first driving cylinder is hinged to the frame. As the connection rod finishing wheel is only fixed on the first connection rod and both the connection rod finishing wheel and the connection rod are located out of the area surrounded by the abrasive belt, the operation of the manipulator will not be hindered by the connection rod finishing wheel, and in the meantime, the connection rod finishing wheel is pressed against the back of the abrasive belt and a curve surface could be polished on the surface of the work piece. Furthermore, the piston rod of the driving cylinder could drive the first connection rod to retract inward to the upper part of one side of the frame. Meanwhile, no much space will be occupied on the frame while the use function is enhanced.
Several connection rod finishing wheels could be provided. In the abrasive belt polishing finisher, the frame is provided with a second connection rod and a second driving cylinder. The second connection rod and the second driving cylinder are located under the connection support and out of the area surrounded by the abrasive belt. One end of the second connection rod is hinged to the frame and the other end thereof is connected with the connection rod finishing wheel within the area surrounded by the abrasive bet. The end of the piston rod of the second driving cylinder is hinged to the second connection rod. The curved surface of the rim of the connection rod finishing wheel on the first connection rod has a curvature different from that of the connection rod finishing wheel on the second connection rod.
The scope of application of the abrasive belt polisher could be increased by using the connection rod finishing wheels. The curvature of the curved surface of the rim of the connection rod finishing wheel on the first connection rod is set different from that of the connection rod finishing wheel on the second connection rod, so that when the operation of the manipulator is hindered by the connection support, the connection rod finishing wheel on the first connection rod or the connection rod finishing wheel on the second connection rod could be selected according to the curvature of the curved surface required by the surface of the work piece. While one connection rod finishing wheel extends out, the other connection rod finishing wheel is in a retracted state.
In the abrasive belt polishing finisher, the connection support is located at the central part of the frame. The driving mechanism includes a telescopic cylinder on the frame. The cylinder body of the telescopic cylinder is fixed on the frame. A telescopic piston is provided within the telescopic cylinder. The telescopic piston passes through the side of the frame and is linked with the connection support. When the connection support has to be pushed out, air is supplied to the cylinder body of the telescopic cylinder from an air supply, and the telescopic piston is pushed out from inside of the cylinder body under the force of the air pressure. As the telescopic piston passes through the side of the frame and is linked with the connection support, when the telescopic piston is pushed out, the connection support could be pushed to a designated position on the back of the abrasive belt. When the connection support does not have to be used or the deformation of the manipulator is hindered by the connection support, the telescopic piston retracts inward to bring the connection support to retract inward therewith, and the connection support is away from the back of the abrasive belt.
In the abrasive belt polishing finisher, the cylinder body of the telescopic cylinder and the telescopic piston are both cylindrical. The telescopic piston has an inner cavity. A rotary motor is fixed within the telescopic piston and the output shaft of the rotary motor extends out from the inside of the telescopic piston and is connected with the connection support. As the rotary motor is located within the telescopic piston, the mounting space on the frame could be saved and a simpler structure is provided. When the telescopic cylinder is pushed out to locate the connection support on the back of the abrasive belt, the rotation of the connection support could be controlled merely by controlling the rotation of the output shaft of the rotary motor and the required support finishing wheel will be selected to be pressed against the back of the abrasive belt.
In the abrasive belt polishing finisher, a positioning cylinder is further fixed within the telescopic piston. Several positioning bores are evenly distributed on the connection support on the same circle using the rotation center thereof as the center of circle. The piston rod of the said positioning cylinder could extend out from the inside of the telescopic piston and insert into the positioning bores. When the telescopic piston is pushed outward to locate the connection support on the back of the abrasive belt, the connection support could be controlled by the rotary motor to rotate until the finishing wheel thereon is pressed against the back of the abrasive belt. In order to guarantee the reliability in operation and prevent the connection support from being collided and influenced, the piston rod of the positioning cylinder within the telescopic piston is controlled to be pushed out and inserted into the positioning bore on the current connection support corresponding to the position of the piston rod of the positioning cylinder, for which the connection support will be held stationary.
In the abrasive belt polishing finisher, the cylinder body of the said telescopic cylinder has a chute opened from the end to the middle on its side. The side of the telescopic piston is connected with a lug which could slide along the chute. The lug is located within the chute and a portion of the lug extends out of the chute. When the lug is pressed against the end of the chute, the connection support is located at the back of the abrasive belt. Air is supplied to the cylinder body of the telescopic cylinder from an air supply. The telescopic piston within the cylinder body is pushed out under the force of the air pressure. The lug connected with the side of the telescopic piston will move along the chute on the side of the cylinder body. When the lug is moved and pressed against the end of the chute, the connection support is exactly located on the inner side of the abrasive belt, which not only ensures the connection support will be accurately pushed to a designated position, but also achieves the position restricting effect to ensure the telescopic piston will not fall off from the cylinder body.
In the abrasive belt polishing finisher, a housing is fixed on the side of the frame opposite to the connection support. The driving mechanism has a spin motor fixed on the end of the housing. A via hole is provided on the side of the frame corresponding to the connection support. A positioning sleeve having an inner cavity is threaded with the via hole. The positioning sleeve is located within the housing and the output shaft of the spin motor is connected with one end of the positioning sleeve. The rotary motor is provided within the positioning sleeve. The output shaft of the rotary motor extends out from the other end of the positioning sleeve and is connected with the connection support. The output shaft of the spin motor is controlled to rotate forward. As the output shaft of the spin motor is linked with the positioning cylinder and the positioning cylinder is threaded with the via hole, the forward rotation of the output shaft of the spin motor will bring the positioning cylinder to extend out from the inside of the housing along the threaded section, and lead the connection support to be on the inner side of the abrasive belt. Thereafter, the output shaft of the rotary motor is controlled to drive the connection support into rotation, so that the finishing wheel on the connection support is pressed against the inner side of the abrasive belt. When the connection support does not have to be used or the deformation of the manipulator is hindered by the connection support, the positioning sleeve could be retracted into the housing merely by controlling the output shaft of the spin motor to rotate anticlockwise.
In the abrasive belt polishing finisher, a housing is fixed on the side of the frame opposite to the connection support. The driving mechanism has a spin motor fixed on the end of the housing. A via hole is provided on the side of the frame corresponding to the connection support. A positioning sleeve having an inner cavity is threaded with the via hole. The end of the output shaft of the spin motor is fixedly connected with a first transmission gear. The positioning sleeve is located within the housing and an inner gear ring is fixed on one end of the positioning sleeve. Several second transmission gears are further provided between the first transmission gear and the inner gear ring. The rotary motor is provided within the positioning sleeve. The output shaft of the rotary motor extends out from the other end of the positioning sleeve and is connected with the connection support.
According to the second aspect of the connection support, in the abrasive belt polishing finisher, the connection support is of a round-disk shape, and connection blocks of a Z-shape are disposed on the connection support. The bottoms of the connection blocks are fixed on the connection support and the support finishing wheels are connected with the upper parts of the connection blocks. The Z-shape connection blocks could make the distance of the connection support extending into the back of the abrasive belt to increase, and reduce the space occupied and shorten the distance of the connection support moving in the axial direction, which ensures the reliability of the structure.
In the abrasive belt polishing finisher, elongated mounting grooves are opened through the bottom of the connection block. Several support posts which are arranged in the radial direction of the connection support and integrated with the connection support are provided at the edge of the connection support. Several mounting holes in a linear arrangement are correspondingly provided on the support post and the connection support. The connection blocks are linked with the support posts through fasteners which could pass through the mounting grooves ( 21 ) and insert into the mounting holes.
By using the mounting grooves at the bottom of the connection block and the mounting holes in a linear arrangement on the support post, the position of the connection block in the direction of the support post could be adjusted. As such, when the rim of the finishing wheel is worn to a small extent by the long-period operation of the finishing wheel fixed on the connection block, the connection block could be moved to offset the wear.
A convex guide strip is disposed at the bottom of the connection block and a guide groove is correspondingly opened on the support post of the connection support. The guide strip and the guide groove are provided to conveniently and rapidly connect the connection block to the support post.
Compared with the prior art, by using the finishing wheel transform mechanism of the abrasive belt polishing finisher of the invention, a curved surface of a different curvature could be polished with a high quality on the work piece. The finishing wheel transform mechanism has a wide scope of application, convenient operation and high operation efficiency. In the meantime, the abrasive belt polishing finisher uses the driving mechanism to achieve the movement of the connection support on the finishing wheel thereon along the axis. The connection support is away from the inner side of the abrasive belt when it is not in use, which largely saves the space of the frame on the inner side of the abrasive belt during polishing, and ensures the manipulator is not affected when it is adjacent to the frame at the back of the abrasive belt. Moreover, the operation of the manipulator could be switched adjacent to the frame of the abrasive belt, which ensures the reliability of polishing and uniformity of polishing precision everywhere on the surface of the work piece. In the abrasive belt polishing finisher, a first connection rod and a second connection rod are respectively hinged to the upper and lower parts on the one side of the frame. The space on the side of the frame will not be occupied whether or not the first connection rod and the second connection rod have to be used. While the space of the frame on the inner side of the abrasive belt is saved, a curved surface can be polished on the surface of the work piece, which provides higher usefulness.
Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will become more fully understood from the detailed description given herein below for illustration only, and thus are not limitative of the present invention, and wherein:
FIG. 1 is a structural diagram of the finishing wheel transform mechanism of the abrasive belt polishing finisher of the invention;
FIG. 2 is a structural diagram of the finishing wheel transform mechanism of the abrasive belt polishing finisher of the invention from another angle of view;
FIG. 3 is a sectional view of the finishing wheel in the finishing wheel transform mechanism of the abrasive belt polishing finisher of the invention;
FIG. 4 is a structural diagram of the finishing wheel transform mechanism of the abrasive belt polishing finisher of the invention being applied to the abrasive belt polishing finisher;
FIG. 5 is a structural diagram of the front surface of the abrasive belt when the finishing wheel of the finishing wheel transform mechanism of the abrasive belt polishing finisher of the invention is pressed against the back of the abrasive belt;
FIG. 6 is a diagram showing the connection support, the first connection rod and the second connection rod are all in a retracted state in the abrasive belt polisher;
FIG. 7 is a side view of FIG. 6 ;
FIG. 8 is a structural diagram showing the finishing wheel on the connection support is pressed against the back of the abrasive belt in the abrasive belt polisher;
FIG. 9 is a back view of FIG. 8 ;
FIG. 10 is a diagram showing the finishing wheel on the first connection rod is pressed against the back of the abrasive belt in the abrasive belt polisher;
FIG. 11 is a diagram showing the connection of the connection support with the telescopic cylinder in the abrasive belt polisher;
FIG. 12 is a back view showing the connection of the connection support with the telescopic piston in the abrasive belt polisher; and
FIG. 13 is a structural diagram of the connection support in the abrasive belt polisher.
DETAILED DESCRIPTION OF THE INVENTION
The embodiments of the invention will be described below and the technical solutions of the invention will be further illustrated in connection with the accompanying figures. However, the present invention shall not be limited to these embodiments.
First Embodiment
As shown in FIGS. 1, 2 and 4 , the abrasive belt polishing finisher of the invention comprises a frame 1 , a driving wheel 2 and a driven wheel 3 provided on the frame 1 , and an abrasive belt 4 covered on the driving wheel 2 and the driven wheel 3 . The finishing wheel transform mechanism on the frame 1 includes a motor 25 , a connection support 5 fixedly connected with the output shaft of the motor 25 at the central section, and three support finishing wheels 6 connected around the connection support 5 . The number of the support finishing wheels 6 could be 2, 4, 5 or more as required. The connection support 5 includes an annular connection part 51 and rod-like support parts 52 in the same number as that of the support finishing wheels 6 . The connection part 51 is covered outside of and fixedly connected with the output shaft of the motor 25 . The inners end of the support parts 52 are integrated with the outer side of the connection part 51 , and the other ends thereof are respectively connected with the support finishing wheels 6 . Three support parts 52 are provided. The support parts 52 diverge outward in the radial direction along the output shaft of the motor 25 . Three support parts 52 are evenly distributed about the output shaft of the motor 25 for which an angle of 120 degrees is formed between every two support parts 52 . Three support finishing wheels 6 are provided and the axis of the support finishing wheel 6 is in the same direction as that of the output shaft of the motor 25 . The support finishing wheel 6 is fixed to the outer end of the support part 52 by means of a screw passing through the axis. Three support finishing wheels 6 are distributed on the same circle centered on the output shaft of the motor 25 .
As shown in FIG. 3 , the support finishing wheel 6 includes a wheel-like body 26 and an annular finishing cover 27 covered outside of the body 26 . The inner side of the finishing cover 27 is fixedly connected with the outer side of the body 26 . A finishing curved surface in contact with the back of the abrasive belt 5 of the polishing finisher is provided on the outer side of the finishing cover 27 . The curvatures of the finishing curved surfaces on the said three finishing covers 27 are gradually increased. In this embodiment, the finishing cover 27 is made of rubber materials and fixedly connected with the body 26 by casting. Three support parts 52 have the same length. Three support finishing wheels 6 have the same diameter and all the axial centers of the three support finishing wheels 6 are located on the same circle centered on the output shaft of the motor 25 .
The finishing wheel transform mechanism of the abrasive belt polishing finisher further comprises a controller and a detection module connected to the controller. The detection module is correspondingly positioned at the motor 25 and the connection support 5 and could detect that a stop signal is sent to the controller when the support finishing wheels 6 along with the connection support 5 rotate to the back of the abrasive belt 5 about the output shaft of the motor 25 . The controller could control the motor 25 to stop working and be positioned after receiving the stop signal.
In this embodiment, the diction module includes a proximity switch 28 and three sensor blocks 29 disposed outside of the motor 25 . One side of the proximity switch 28 for detecting adjacent objects is faced to the back of the abrasive belt 5 . Each of the three sensor blocks 29 is fixedly connected with the support part 52 and located on one side of the motor 25 correspondingly, and the sensor blocks 29 could move to a position opposite to the proximity switch 28 when they rotate to the back of the abrasive belt 5 along with the support finishing wheels 6 . The motor 25 could be a brake motor 25 , in which the brake generally means an electro-magnetic mechanical brake device at the back end of the servo motor 25 , which is mounted at the back end of the motor 25 . The motor 25 is braked and the main shaft of the motor 25 is locked to be positioned through the brake sheet acted on the main shaft of the motor 25 in operation.
With reference to FIG. 4 , when the finishing wheel transform mechanism of the abrasive belt polishing finisher of the invention is in use, the finishing wheel transform mechanism is mounted on the back of the abrasive belt 5 in the polishing finisher to control the driving device of the polishing finisher to drive the abrasive belt 5 in transmission, for which only the ordinary surface of the work piece could be finished. With respect to special curved surfaces to be finished, the operator could select corresponding support finishing wheels 6 based upon the curvature of the surface to be polished of the work piece to be processed. The operation of the motor 25 could be controlled to drive the connection support 5 and the support finishing wheels 6 around the connection support 5 to rotate to the abrasive belt 5 around the output shaft of the motor 25 .
When the support finishing wheel 6 rotates to the back of the abrasive belt 5 , the sensor block 29 connected to the support part 52 correspondingly connected with the support finishing wheel 6 moves to a position opposite to the proximity switch 28 . A stop signal is sent to the controller when the proximity switch 28 detects the object is adjacent. The controller controls the brake motor 25 to stop working and lock the main shaft. Meanwhile, referring to FIG. 5 , the outer side of the support finishing wheel 6 pressed against the abrasive belt 5 is beyond the original position of the abrasive belt 5 . The abrasive belt 5 is closely pressed on the finishing cover 27 outside of the support finishing wheel 6 and a shape 43 identical to the finished curved surface outside of the finishing cover 27 is formed on the front surface of the abrasive belt 5 . The surface of the work piece could thus be finished by the abrasive belt 5 in transmission. The support finishing wheel 6 rotates by itself while the abrasive belt 5 is in transmission, so that rolling friction is formed between the finishing cover 27 and the back of the abrasive belt 5 to reduce abrasion.
After finishing is completed, if support finishing wheels 6 of other curvatures are required, the controller could control the motor 25 again to discharge the brake and activate. The motor 25 could turn by 120 degrees or 240 degrees to rotate the corresponding support finishing wheel 6 to the back of the abrasive belt 5 . The specific operation is the same as that described above. When three support finishing wheels 6 are not required to be used any more, the controller could control the motor 25 to drive the connection part 51 rotate by 60 degrees. In the meantime, two adjacent support finishing wheels 6 are both close to but not in contact with the back of the abrasive belt 5 , and the abrasive belt could be in normal operation. The control of the controller could be set as desired. Corresponding control commands could be provided to the controller by adding operation buttons or automatic control could be performed by software program input into the controller in advance.
Second Embodiment
The second embodiment is substantially the same as the first embodiment except the positioning of the detection module and the connection support. The detection modules includes infrared receiving units fixedly connected with the outer side of the motor 25 and infrared emitting units in the same number as that of the support finishing wheels 6 . The infrared emitting units are corresponding to the three support parts 52 respectively and move to the positions corresponding to the infrared receiving units when they rotate to the back of the abrasive belt 5 along with the connection support 5 . Here, in order to set aside the reaction time for control, the detection position could be put ahead by some distance, and the specific distance could be determined as required. Alternatively, a servo motor or stepper motor for precise control of the positioning operation could be used. The rotation angle could be precisely positioned by the controller to control the precise positioning of the support finishing wheels 6 . The positioning of the connection support 5 could be achieved by using a solenoid valve and several via holes opened on the connection support 5 . The coils of the solenoid valve are connected to the supper supply loop of the motor 25 . When the said support finishing wheels 6 rotate to the back of the abrasive belt, the power supply loop stops supplying power to the motor and starts to supply power to the solenoid valve, to extend the outer end of the valve rod of the solenoid valve into one of several via holes.
Third Embodiment
As shown in FIGS. 6, 8 and 10 , the abrasive belt polishing finisher refers to an improvement to the finisher according to the first embodiment. The abrasive belt polishing finisher comprises a frame 1 and a driving wheel 2 and driven wheels 3 provided on the frame 1 , and an abrasive belt 4 covered on the driving wheel 2 and the driven wheels 3 . A driving mechanism connected with the finishing wheel transform mechanism of the first embodiment is further provided on the frame 1 . The connection support 5 in the finishing wheel transform mechanism could move between a first position and a second position along the axis of the support finishing wheels 6 . In the first position, the driving mechanism drives the connection support 5 in movement to disengage the support finishing wheels 6 from the abrasive belt and locate the support finishing wheels out of an area surrounded by the abrasive belt. In the second position, the driving mechanism drives the connection support to move into the area surrounded by the abrasive belt and makes the support finishing wheels 6 right toward the back of the abrasive belt, and the support finishing wheels 6 could be in contact with the abrasive belt driven by the finishing wheel transform mechanism. Connection rod finishing wheels 30 movable between the polishing position and the reset position are further provided in the area surrounded by the abrasive belt. In the polishing position, the connection support moves to the first position to disengage the support finishing wheels 6 from the abrasive belt and locate the support finishing wheels 6 out of the area surrounded by the abrasive belt. The connection rod finishing wheels move to the back of the abrasive belt and contact with the abrasive belt. In the reset position, the connection rod finishing wheels disengage from the back of the abrasive belt to return to the area surrounded by the abrasive belt. The connection rod finishing wheels are respectively located above and under the connection support. The position of the connection rod finishing wheels in contact with the abrasive belt after moving is identical to that of the support finishing wheels 6 in contact with the abrasive belt after the connection support moves.
In particular, the connection support 5 is provided at the central section on one side of the frame 1 . Several support finishing wheels 6 evenly distributed using the rotation center of the connection support 5 as the center of circle, are connected with the peripheral of the connection support 5 . The rim of each of the support finishing wheels 6 has a curved surface of a different curvature. The upper part of the side of the frame 1 provided with the connection support 5 has a positioning post 24 close to the back of the abrasive belt 5 . The driven wheel 3 is connected with the positioning post 24 and a first connection rod 7 is coupled with the positioning post 24 . The first connection rod 7 is connected between the driven wheel 3 and the side of the frame 1 . The end of the first connection rod 7 is connected with a connection rod finishing wheel 30 . A first driving cylinder 8 is provided at the upper part of the frame 1 . The end of the piston rod of the first driving cylinder 8 is hinged to the first connection rod 7 .
The driving wheel 2 is located at the lower part of the side of the frame 1 provided with the connection support 5 close to the back of the abrasive belt 4 . A second connection rod 9 is hinged to the frame 1 adjacent to the driving wheel 2 . The end of the second connection rod 9 is connected with a connection rod finishing wheel 30 . A second driving cylinder 10 is provided at the lower part of the said side of the frame 1 . The end of the piston rod of the second driving cylinder 10 is hinged to the second connection rod 9 . The connection rod finishing wheel 30 on the first connection rod 7 has a curvature different from that of the curved surface of the rim of the connection rod finishing wheel 30 on the second connection rod 9 .
As shown in FIG. 8 , the connection support 5 is of a round-disk shape. Several support posts 19 diverging outward using the rotation center of the connection support 5 as the center of circle, are provided on the rim of the connection support 5 . The support post 19 is connected with a connection block 20 of a Z-shape. A convex guide strip is disposed at the bottom of the connection block 20 . A guide groove 23 is correspondingly opened on the support post 19 of the connection support 5 . The guide strip could slide into the guide groove 23 . Elongated mounting grooves 21 are opened at the bottom of the connection block 20 . Several mounting holes 22 in linear arrangement are provided correspondingly on the support post 19 . The connection block 20 is fixed to the support post 19 by using the bolts passing through the mounting grooves 21 and inserting into the mounting holes 22 . The position of the connection block 20 along the extending direction of the support post 19 could be adjusted by using the mounting grooves 21 .
As shown in FIGS. 1-7 , a driving mechanism is further provided on the frame 1 . The driving mechanism has a telescopic cylinder 11 on the other side of the frame 1 opposite to the connection support 5 . The cylinder body 12 of the telescopic cylinder 11 is fixed on the frame 1 . A telescopic piston 13 is provided within the cylinder body 12 of the telescopic cylinder 11 . The telescopic piston 13 passes through the side of the frame 1 and is linked with the connection support 5 . The connection support 5 could move along the axis of the support finishing wheel 6 to the inner side of the abrasive belt 4 driven by the driving mechanism, so that the rim of the support finishing wheel 6 thereon is opposite to the inner side of the abrasive belt 4 .
Referring to FIGS. 6 and 7 , the cylinder body 12 of the telescopic cylinder 11 and the telescopic piston 13 are both cylindrical. The cylinder body 12 of the telescopic cylinder 11 has a chute 17 opened from the end to the middle on its side. The side of the telescopic piston 13 is connected with a lug 18 . The lug is located within the chute 17 and a portion of the lug 18 extends out of the chute 17 . When the lug 18 is pressed against the end of the chute 17 , the connection support 5 moves to the inner side of the abrasive belt 4 along the axis of the support finishing wheels 6 thereon.
As shown in FIG. 7 , the telescopic piston 13 has an inner cavity. A rotary motor 254 is fixed within the telescopic piston 13 . The output shaft of the rotary motor 254 extends out from the inside of the telescopic piston 13 and is linked with the connection support 5 . The output shaft of the rotary motor 254 drives the connection support 5 into rotation. The output shaft of the rotary motor 254 is the rotation center of the connection support 5 .
A positioning cylinder 15 is further fixed within the telescopic piston 13 . Several positioning bores 16 are evenly distributed on the connection support 5 on the same circle using the rotation center as the center of circle. After the support finishing wheels 6 on the connection support 5 rotate to and are pressed against the inner side of the abrasive belt 4 , the piston rod of the positioning cylinder 15 will extend out from the inside of the telescopic piston 13 and insert into the positioning bore 16 corresponding to the piston rod of the positioning cylinder 15 on the current connection support 5 .
As shown in FIGS. 1 and 2 , the abrasive belt 4 is covered on the driving wheel 2 and driven wheel 3 . The driving wheel 2 rotates to drive the abrasive belt 4 into rotation therewith. When a curved surface does not have to be polished on the surface of the work piece, the connection support 5 is at a position away from the inner side of the abrasive belt 4 , the first connection rod 7 and the second connection rod 9 are in a telescopic state, and the work piece is held by the manipulator in cooperation with the abrasive belt 4 of the polisher into contact with the abrasive belt 4 in rotation.
As shown in FIGS. 3 and 4 , when a curved surface has to be polished on the surface of the work piece, the telescopic piston 13 within the telescopic cylinder 11 is controlled to be pushed out. The lug 18 on the side of the telescopic piston 13 slides along the chute 17 on the side of the cylinder body 12 of the telescopic cylinder 11 . When the lug 18 is pressed against the end of the chute 17 , the telescopic piston 13 pushes the connection support 5 to a position right on the inner side of the abrasive belt 4 . In the meantime, the rim of the support finishing wheel 6 of the connection support 5 is opposite to the inner side of the abrasive belt 4 . Thereafter, the support finishing wheels on the connection support 5 are selected according to the curvature of the curved surface to be polished on the surface of the work piece. The rotary motor 254 within the telescopic piston 13 is controlled to rotate. The output shaft of the rotary motor 254 drives the connection support 5 into rotation. When the support finishing wheel 6 selected on the connection support 5 is pressed against the inner side of the abrasive belt 4 , the rotary motor 254 stops rotating. The support finishing wheel 6 selected on the connection support 5 forms a shape identical to the rim of the said support finishing wheel 6 on the surface of the abrasive belt 4 . The work piece is held by the manipulator into contact with the abrasive belt 4 there, to polish the curved surface of a required curvature.
In order to prevent the connection support 5 from self-rotating resulted from a number of factors including collision during polishing, after the support finishing wheel 6 selected on the connection support 5 is pressed against the inner side of the abrasive belt 4 , the positioning cylinder 15 within the telescopic piston 13 is controlled to work, and the piston rod of the positioning cylinder 15 extends outward and inserts into the positioning bore 16 corresponding to the piston rod of the positioning cylinder 15 on the current connection support 5 , so that the connection support 5 is locked and could not rotate. Moreover, when a curved surface of a different curvature is to be polished on the surface of the work piece, the piston rod of the positioning cylinder 15 is only required to exit from the positioning bore 16 on the connection support 5 . Thereafter, the support finishing wheels 6 on the connection support 5 are selected and the rotation step of the connection support 5 is repeated.
Referring to FIG. 5 , when the manipulator is adjacent to the frame 1 on the inner side of the abrasive belt 4 , the manipulator will collide with the connection support 5 on the inner side of the abrasive belt 4 . However, when a curved surface is polished on the surface of the work piece, the piston rod of the positioning cylinder 15 is firstly controlled to be retracted, the output shaft of the rotary motor 25 then rotates to disengage the support finishing wheel 6 on the connection support 5 from the inner side of the abrasive belt 4 , and then the telescopic piston 13 brings the connection support 5 to retract inward therewith. The connection support moves inward along the axis of the support finishing wheel 6 and away from the back of the abrasive belt 4 , for which the frame 1 on the back of the abrasive belt 4 is hung and the manipulator will not be affected. Thereafter, in order for a curved surface to be polished on the surface of the work piece, the connection rod finishing wheel 30 on the first connection rod 7 and the second connection rod 9 could be selected according to the curvature of the curved surface. For example, when the connection rod finishing wheel 30 on the first connection rod 7 is selected, the second connection rod 9 is still in the retracted state. The piston rod of the first driving cylinder 8 is controlled to be pushed outward, and the first connection rod 7 rotates outward around the positioning post 24 under the push force until the connection rod finishing wheel 30 at the end of the first connection rod 7 is pressed against the back of the abrasive belt 4 , so that the curved surface could be polished on the work piece again. As both the first connection rod 7 and the first driving cylinder 8 are disposed on the top of one side of the frame 1 , even if the first connection rod 7 rotates outward until the connection rod finishing wheel 30 thereon in pressed against the back of the abrasive belt 4 , the frame 1 at the back of the abrasive belt 4 is hung. Therefore, the work piece could be polished and the manipulator will not be affected.
When the connection rod finishing wheel 30 on the second connection rod 9 has to be used, the piston rod of the first driving cylinder 8 is controlled to bring the first connection rod 7 to retract therewith, the connection rod finishing wheel 30 on the first connection rod 7 is separate from the back of the abrasive belt 4 , and the first connection rod 7 rotates inward and retunes to the upper part of one side of the frame 1 . Then the piston rod of the second driving cylinder 10 pushes the second connection rod 9 outward to rotate outward about the hinge point. The connection rod finishing wheel 30 on the second connection rod 9 is pressed against the back of the abrasive belt 4 to polish the work piece.
The abrasive belt polisher uses the driving mechanism to move the connection support 5 along the axis of the support finishing wheel 6 thereon. When the abrasive belt polisher is not in use, a large amount of space of the frame 1 on the inner side of the abrasive belt 4 could be saved, which could ensure the frame 1 is not affected when the manipulator is close to the inner side of the abrasive belt 4 , and enhance the polishing reliability of the work piece and the uniformity of the polishing precision of the work piece. The first connection rod 7 and the second connection rod 9 are respectively hinged to the upper and lower parts of one side of the frame 1 . As such, a large amount of space is left at the frame 1 on the inner side of the abrasive belt 4 , and in the meantime, the curved surface could polished on the work piece, thereby providing better usefulness.
Fourth Embodiment
The structure and principle of this embodiment are substantially the same as those of the third embodiment except that a housing is fixed on the side of the frame 1 opposite to the connection support 5 . The driving mechanism has a spin motor fixed on the end of the housing. A via hole is provided on the side of the frame 1 corresponding to the connection support 5 . A positioning sleeve having an inner cavity is threaded with the via hole. The positioning sleeve is located within the housing and the output shaft of the spin motor is connected with one end of the positioning sleeve. A rotary motor 25 is provided within the positioning sleeve. The output shaft of the rotary motor 25 extends out from the other end of the positioning sleeve and is connected with the connection support 5 .
The output shaft of the spin motor is controlled to rotate forward. As the output shaft of the spin motor is linked with the positioning sleeve and the positioning sleeve is threaded with the via hole, the forward rotation of the output shaft of the spin motor will lead the positioning sleeve to extend outward along the threaded section from the inside of the housing, and lead the connection support 5 to be on the inner side of the abrasive belt 4 . Thereafter, the output shaft of the rotary motor 25 is controlled to drive the connection support into rotation, so that the support finishing wheel 6 on the connection support 5 is pressed against the inner side of the abrasive belt 4 . When the connection support 5 does not have to be used or the deformation of the manipulator is hindered by the connection support 5 , the positioning sleeve could be retracted into the housing merely by controlling the output shaft of the spin motor to rotate anticlockwise.
Fifth Embodiment
The structure and principle of this embodiment are substantially the same as those of the third embodiment except that a housing is fixed on the side of the frame 1 opposite to the connection support 5 . The driving mechanism has a spin motor fixed on the end of the housing. A via hole is provided on the side of the frame 1 corresponding to the connection support 5 . A positioning sleeve having an inner cavity is threaded with the via hole. The end of the output shaft of the spin motor is fixedly connected with the first transmission gear. The positioning sleeve is located within the housing and an inner gear ring is fixed on one end of the positioning sleeve. Several second transmission gears are further provided between the first transmission gear and the inner gear ring. A rotary motor 25 is provided within the positioning sleeve. The output shaft of the rotary motor 25 extends out from the other end of the positioning sleeve and is connected with the connection support 5 .
When the output shaft of the spin motor rotates forward, the first transmission gear at the end thereof drives the second transmission gears which drive the inner gear ring into rotation. As the inner gear ring is fixed at the end of the positioning sleeve, the second transmission gears drive the positioning sleeve into rotation. The positioning sleeve is threaded with the via hole on the side of the frame 1 . As a result, the positioning sleeve will move in the axial direction relative to the via hole, so that the positioning sleeve is pushed outward from the inside of the housing, and the connection support 5 is located on the inner side of the abrasive belt 4 . Thereafter, the rotary motor 25 within the positioning sleeve is in operation, which eventually drives the connection support 5 into rotation until the support finishing wheel 6 thereon is pressed against the inner side of the abrasive belt 4 . When the connection support 5 does not have to be used or the deformation of the manipulator is hindered by the connection support 5 , the positioning sleeve could be retracted into the housing merely by controlling the output shaft of the spin motor to rotate anticlockwise.
The embodiments described herein are merely illustrative of the spirit of the invention. It is obvious for those skilled in the art to make various modifications, supplements or alternatives to these embodiments without departing from the spirit of the invention or the scope as defined by the appended claims.
LIST OF REFERENCE NUMERALS
1 Frame
2 Driving Wheel
3 Driven Wheel
4 Abrasive Belt
43 Shape the same as the Finished Curved Surface
5 Connection Support
6 Support Finishing Wheel
30 Connection Rod Finishing Wheel
7 First Connection Rod
8 First Driving Cylinder
9 Second Connection Rod
10 Second Driving Cylinder
11 Telescopic Cylinder
12 Cylinder Body
13 Telescopic Piston
14 Rotary Motor
15 Positioning Cylinder
16 Positioning Bore
17 Chute
18 Lug
19 Support Post
20 Connection Block
21 Mounting Groove
22 Mounting Hole
23 Guide Groove
24 Positioning Post
25 Motor
51 Connection Part
52 Support Part
26 Body
27 Finishing Cover
28 Proximity Switch
29 Sensor Block
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The invention discloses an abrasive belt polishing finisher in the field of mechanical technology, which addresses inconvenient operation of the existing polishing finishers. The abrasive belt polishing finisher includes a motor and a connection support. The central section of the connection support is fixedly connected with the output shaft of the motor. Several self-rotable connection support finishing wheels are provided around the connection support. The curve surface of the rim of each of the support finishing wheels has a different curvature. Each connection support finishing wheel is distributed on the same circle centered on the output shaft of the motor. The connection support is driven by the motor into rotation to press and position one of the connection support finishing wheels against the back of the abrasive belt in the polishing finisher. The abrasive belt polishing finisher could satisfy continuous polishing treatment for different curved surfaces.
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The present application is a continuation-in-part application of pending application Ser. No. 944,989, now U.S. Pat. No. 4,792,184 filed Dec. 2, 1986, entitled CONTAINER HOLDER FOR A VEHICLE to Lindberg et al. The subject matter of this prior application is incorporated herein by reference.
BACKGROUND OF THE INVENTION
The present invention relates to holders for a container and particularly to one for use in connection with a vehicle and more particularly an armrest within a vehicle.
There exists a variety of cup holders or container holders utilized for supporting cups, cans and other beverage containers in a vehicle such that the vehicle occupants can support such beverage containers while in the vehicle. U.S. Pat. No. 4,417,764 issued Nov. 29, 1983 is representative of one cup holder structure which is incorporated in the armrest of a vehicle and which can accommodate such containers. U.S. Pat. No. 3,326,445 discloses a disposable container holder for use on a car seat. U.S. Pat. Nos. 3,497,076 and 4,040,659 also disclose cup holders which move from a storage position within a support structure in an automobile to a use position.
Although these various cup holders are useful for single or limited sized containers, the system of the present invention is adapted to accommodate a variety of different sized beverage containers such as cans, coffee mugs, large cups and the like.
SUMMARY OF THE PRESENT INVENTION
Container holders embodying the present invention includes a support structure within a vehicle for the holder and a holder movably mounted within the support for movement between stored and use positions. The holder includes a container supporting element extending in a generally horizontal plane when in a use position with the element including means defining an aperture of adjustable dimensions for engaging the sidewalls of a beverage container and a floor which is movable between a raised stored position and a lowered use position.
In one embodiment of the invention, the means for defining an aperture comprises a plurality of resilient members extending inwardly from an edge of an aperture formed in the horizontal support element. In a preferred embodiment of the invention, the cup holder is mounted within an armrest of a vehicle and can be pivoted or otherwise movably mounted thereto between a stored position within the armrest and a use position extended from the armrest.
These and other features, objects and advantages of the present invention will become apparent upon reading the following description thereof together with reference to the accompanying drawings in which:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a right side elevational view of an armrest incorporating a container supporting member shown partly in cross-section and partly in phantom form;
FIG. 2 is a top plan view of the structure shown in FIG. 1 partly broken away to show the container support member in the stored position;
FIG. 3 is a top plan view partly broken away of the structure shown in FIG. 2 showing in the container support member in an extended use position;
FIG. 4 is an enlarged fragmentary perspective view of the container support member;
FIG. 5 is an exploded fragmentary view of a armrest incorporating a container supporting member of the present invention;
FIG. 6 is a top plan view of the container holder shown in FIG. 5; and
FIG. 7 is a cross sectional view taken along section lines VII--VII in FIG. 6 partly in phantom form showing the operation of the movable floor of the container holder.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring initially to FIG. 1 there is shown an armrest 10 which is secured to a vehicle 12 by one or more suitable mounting brackets 14. In the embodiment shown, bracket 14 pivotally mounts the armrest to the vehicle through pivot mounting member 15 such that the entire armrest can be lowered for use as shown, or raised for storage. The armrest 10 includes a lower storage housing 16 which defines an interior storage compartment 17. The armrest also includes a cover 18 which is pivoted along its rear edge to the rear of housing 16 such that it can be moved between a closed position shown in phantom form in FIG. 1 and an open position shown in solid form in FIG. 1 by pivoting in a direction indicated by arrow A. Pivotally mounted to the forward edge of the inside of compartment 17 near the front wall 19 of the housing 16 is a container holder 20 embodying the present invention.
The container holder 20 comprises a generally planar container supporting element 22 having a central circular aperture 24 extending downwardly therethrough and having a diameter slightly larger than the diameter of the largest container desired to be held therein. The support element 22 integrally includes in the preferred embodiment four arcuate sector shaped resilient cup support members 21, 23, 25 and 27 which are equally spaced around the periphery of aperture 24 and which project partially inwardly toward the center of the aperture. In the preferred embodiment, the thickness of members 21, 23, 25 and 27 is substantially thinner than that of the support element 22 to provide, in effect, resilient flaps which will easily deflect under the influence of the downward pressure of a container. Support element 22 also includes in the preferred embodiment a cup-shaped floor support 30 as best seen in FIG. 1 which includes a circular floor 32 for supporting the bottom of a container while the resilient flaps support the sidewalls at equally spaced intervals. When containers are positioned in holder 20, the sidewalls are supported by the inner lips 26 of the segments 21, 23, 25 and 27 in spaced relationship around the periphery of the container and in vertical spaced relationship to the floor support 32. This stabilizes the container when inserted into the holder and yet the resilient segments allow easy removal of the container.
Element 22 includes a pair of rearwardly projecting arms 34 and 36 which are pivotally coupled by pivot pins 35 and 37, respectively to the sidewalls 11 and 13 of housing 16. Thus, the holder 20 can be pivoted to a stored position shown in FIG. 2 and in phantom form in FIG. 1 and concealed by the cover 18 of armrest assembly 10 or pivoted outwardly to a horizontally extending use position as illustrated in FIGS. 1 and 3 for receiving a container. In the stored position, the edges of the rectangular element 22 are supported on the tops of sidewalls 11 and 13 which are covered by a suitable padded upholstery material 28 to conform the armrest to the vehicle's interior. In the use position typically the cover 18 of the armrest will be closed and the rearwardly extending arms 34 and 36 include a "S" shaped curved section 38 as best seen in FIG. 1 to conceal the pivot connections 35 and 37 within the housing 16 to allow the arms to be supported on the top lip 19' of the front wall 19 of housing 16 as best seen in FIG. 1.
The cup holder 20 is integrally formed of a suitable polymeric material such as expanded polyvinyl chloride and can be molded as a single piece including the pivot rods 35 and 37. Legs 34 and 36 are sufficiently resilient to allow the legs to be inwardly deflected for snap fitting them into apertures formed in walls 11 and 13 of housing 16. In place of the stationary floor 32 a movable floor section can be employed to provide greater stability for supporting particularly taller containers. Such construction is shown in the embodiment shown in FIGS. 5-7 now described.
The cup holder 40 of this embodiment of the invention is mounted to the armrest 10 shown in detail in FIGS. 1-3 in the same manner as the first embodiment by the utilization of a pair of outwardly extending pivot pins 42 and 44 integrally formed on the upper housing member 46 of cup holder 40. Pins 42 and 44 extend outwardly from ends of arms 41 and 43, respectively which are offset and include a U-shaped channel 45 extending under the junction of the arms and the generally rectangular body of housing 46 as best seen in FIGS. 5 and 7 such that the surface of channel 45 will rest on the top lip 19' of armrest 10 when in an extended use position which is substantially identical to that shown in the embodiment of FIG. 1.
Housing 46 is generally rectangular including an upper surface 48 and a downwardly extending skirt 49. A circular aperture 50 is formed through the upper surface 48 and includes a pair of arcuate slots 52 and 54 extending towards the rear corners of housing 46 to receive handles of containers such as cups. Positioned below and aligned with upper housing 46 is a resilient foam rubber cup retaining member 60 which is generally rectangular and includes four equally spaced arcuate arms 62-65 which grips the sidewalls of a container in the same manner as in the embodiment shown in FIGS. 1-4. The foam pad 60 is compressed between the lower surface of top 48 of member 46 and the upper surface of lower housing 80 as best seen in FIG. 7 once the cup holder 40 is assembled.
Lower housing 80 also is generally rectangular and includes an upper surface 82 and downwardly depending skirt 84 extending around the peripheral edges of the rectangular plate 82. The lower housing 80 also includes a generally cylindrical aperture 86 formed downwardly through the center thereof conforming to the shape of aperture 50 of the upper housing 46 and includes a pair of elongated downwardly extending arcuate slots 85 and 87 interrupting the cylindrical sidewall 83 of aperture 86. At the bottom of the cylindrical sidewall 83 of aperture 86 there is provided an inwardly projecting lip 88 for retaining the movable floor support 70 in place as described below. As seen in FIG. 7, member 80 is of two piece construction with the cylindrical sidewall 83 separately formed and secured to the outer skirt 84 and lip 88 of the housing. The two pieces 83 and 84 are bonded together during assembly in a conventional manner.
The movable floor section 70 of the cup holder 40 includes a generally cup-shaped member having a floor 72 and a cylindrical sidewall 74 with a plurality of serrations 75 formed through the sides and extending partially down the sides to define flexible fingers 76 having outwardly projecting tips 77. Fingers 76 are molded such that tips 77 extend slightly beyond the outer edge of a circular rim 78 formed along the top edge of cylindrical wall 74 to provide frictional engagement with the sidewall 83 of lower housing 80. This contact of tips 77 of fingers 76 at spaced locations around the periphery of rim 78 stabilizes the movement of and provides a sliding interfit between member 70 and housing 80. Thus, movable floor 70 can be raised to a position shown in phantom lines in FIG. 7 for compact storage of the cup holder or pushed downwardly into a use position shown in solid lines in FIG. 7. Floor 72 includes the printed indicia 90 "PUSH" formed at the center of floor 72 as seen in FIG. 6 to indicate to the user that the floor is movable downwardly for providing a greater vertical spacing between the upper surface of floor 72 and the engagement by edges 62-65 of foam pad 60 thereby providing greater stability for holding containers. Lip 78 as best seen in FIG. 7 engages the inwardly projecting lip 88 of housing 80 for holding the movable floor member 70 within the confines of the upper housing 46 and lower housing 80.
It will become apparent to those skilled in the art the various modifications to the preferred embodiments of the invention described herein can be made without departing from the spirit or scope thereof as defined by the appended claims.
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A container holder for a vehicle is stored in an armrest and can be moved to a use position exposing a container supporting element. The container supporting element includes an aperture with adjustable dimensions for engaging the sides of different diameter containers and a movable floor permitting compact storage and improved stability for holding containers.
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BACKGROUND OF THE INVENTION
The present invention relates generally to agricultural implements, and more particularly relates to apparatus for transferring and metering chemicals from one container to another container.
Modern farming practices indicate that herbicides, insecticides, fertilizers and other chemical solutions will be used with increasing frequency to realize optimum crop yields. These chemicals are for the most part applied by the farmer.
To realize the most economical purchase of agricultural chemicals, the farmer will buy in bulk amounts. To apply the chemicals to the crops or soil requires that the desired amount of concentrate or solution be transferred from the bulk storage container to the application apparatus. Because many of the agricultural chemicals can present health hazards when contacted or inhaled over a period of time, the transferring process can be hazardous. Magnifying the problem is the fact that the farmer must store, transfer and apply several different chemicals throughout the growing season.
Existing transfer apparatus include manual and powered transfer pumps. The manual type of pump is usually portable and includes an inlet hose or pipe which is inserted into the bulk storage container. The pump handle is then manually turned and the flow directed through an outlet hose or pipe into the receiving container. With this type of pump, the farmer is exposed to the chemical fumes and solution during the entire transfer process and cannot be confident that the volume desired has been transferred. The powered type of pump generally presents less of an exposure problem for the farmer since he need only insert the inlet and outlet hoses in the proper containers and start the motor or power source. However, these pumps do not provide metering indicators which would allow the farmer to transfer only the required amount of expensive chemical to the receiving container. Powered pumps also require a powering source of energy and therefore are bulky or inconvenient, presenting time consuming problems when several chemicals are to be transferred, mixed or taken from different storage locations.
SUMMARY OF THE INVENTION
To overcome these problems, applicant has provided in the present invention a portable transfer and metering apparatus having means for automatically transferring a desired volume of chemicals or fluid from one container to another.
The principal object of the invention is to provide a pump having a metering control means which permits the operator to dial in the desired chemical volume to be transferred and which will then shut down the pump upon the completed transfer of that volume.
Another object of the present invention is to provide a transferring pump which can easily be coupled to the chemical supply and receiving containers without requiring unnecessary physical exposure of the operator to the chemicals transferred.
It is further an object of the present invention to provide a compact and portable transfer and metering apparatus which includes its own portable power source.
A more specific object of the present invention includes the provision of a metering control means which will not indicate transfer of chemical volume when the pump is not transferring fluid.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic and diagrammatic view illustrating the transfer and metering apparatus.
FIG. 2 is a side view of the mechanical drive mechanism for the counter cam.
FIG. 3 is an enlarged end view of the counter indicator.
FIG. 4 is a diagram illustrating the electrical circuit for the transfer and metering apparatus shown in FIG. 1.
FIG. 5 is a diagram illustrating a modified electrical circuit for the transfer and metering apparatus.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings, there is illustrated in FIG. 1 a portable transferring and metering apparatus including a portable electric power source or twelve volt battery 10, a motor 12, a motor driven fixed displacement pump 14, a counter cam 16 driven by the pump 14, counter means 18 including a pre-settable volume indicator 20, a source control means 22, relay means 24 and a reset means 26 for shutting down the pump 14 when the preset volume has been transferred.
The preferred embodiment includes the portable power source 10 connected by a line 28 to a suitable circuit breaker 30. From the circuit breaker 30 a line 32 leads to the first terminal 34 of a first relay 36. Line 38 leads from the first terminal 34 of the first relay 36 to a switch means 40 which includes a lever switch 42 activated by the counter cam 16 in fixed relationship to the volume displaced by the pump 14. The exact manner in which the counter cam 16 is powered by the pump 14 will be explained hereinbelow. From the lever switch 42 a line 44 leads to a pressure sensitive means or low pressure switch 46 which is inserted into an outlet line 48 of the pump 14. Leading from the low pressure switch 46 is line 50 which connects with a solenoid coil 52 having a slidable core 54 therein. With each closing of the lever switch 42, a circuit will be completed from the counter means 18 to the solenoid coil 52. As the circuit is completed, the slidable core 54 will shift moving the indicator dial gears 56 to reflect a one-tenth gallon change in pumped volume.
Also leading from the first terminal 34 of the first relay 36 is line 58 which connects to the first terminal 34 a power switch 60. The power switch 60 is in turn connected by line 62 to a reset switch 64 which is mechanically coupled with the indicator dials 56 to be in an open position when the indicator dials 56 read zero. Also connected to the power switch 60 by a line 66 is an electric light 68, activated whenever the power switch 60 is moved to an "on" position.
From the reset switch 64, a line 70 leads to a first terminal 72 of a second relay 74. Leading from the first terminal 72 of this second relay 74 is a line 76 which is connected to a start means or starter button 78. Line 80 leads from the starter button 78 and is connected to the coil terminal 82 of the second relay 74. From this coil terminal 82, a line 84 is connected with a second terminal 86 of the second relay 74. Line 88 connects the second terminal 86 of the second relay 74 to the coil terminal 90 of the first relay 36. To the second terminal 92 of the first relay 36, line 94 leads to the motor 12.
As best viewed in FIG. 2, the motor 12 is mechanically coupled to the pump 14 by belt 96 trained over motor pulley 98 and the pump pulley 100. A pump shaft 102 drivingly rotates a pump sprocket 104 having chain 106 trained over it and around cam sprocket 108 secured to cam shaft 110 to drivingly rotate the cam 16 in fixed relation to the pump 14 displacement. In the present embodiment, the cam 16 will rotate one revolution to close the circuit between lines 38 and 44 when the pump 14 has transferred one-tenth gallon of chemicals or fluid. The cam 16 is secured to the cam shaft 110 for rotation about an eccentric path and contacts roller 112 which is rotatably attached to the lever switch 42.
The transferring and metering apparatus is compact and portable and in operation can be easily moved to the chemical supply 114 which is to be transferred. To operate, the farmer will first couple the inlet line 116 with the desired chemical or fluid supply 114 and then couple the outlet line 48 with the fluid deposit tank or pipe 118. The desired volume to be transferred will be manually dialed into the indicator 20 and is reflected in the present embodiment in tenths of a gallon. As a value is dialed onto the indicator 20, the reset switch 64 will move into contact with the line 62 leading in from the power switch 60. The power switch 60 is then flipped to the "on" position and the start button 78 then pushed. A separate start button 78 is provided to activate the pump 14 and assures that an accidental start up does not occur when the power switch 60 is moved to an "on" position.
After the starter button 78 is pushed, the coil terminal 82 of the second relay 74 is activated by the power source 10 and causes the coil's slidable core plate 122 to move into a latched position and connect the first 72 and second 86 terminals of the second relay 74. Feedback from the first terminal 72 of the second relay 74 then flows through the core plate 122, the terminal 86 and the line 84 to the coil terminal 82 of the second relay 74 to latch the coil in the activated position. Connection of the first terminal 72 of the second relay 74 with the second terminal 86 of the second relay 74 causes the current to flow through the line 88 to the coil terminal 90 of the first relay 36 and latch the slidable core plate 124 of the first relay 36 to connect the terminals 34 and 92 of the first relay 36. Power is then provided from the power source 10 through the first terminal 34 of the first relay 36 to the second terminal 92 of the first relay 36 and through line 94 to activate the motor 12.
As the pump shaft 102 is drivingly powered by the motor 12, the cam shaft 110 will rotate, the attached cam 16 will rotate against the roller 112 and the lever switch 42 will be moved in an arc about its pivotal connection 126 to complete the circuit from the power source 10 to the pressure sensitive switch 46 with each cam rotation. As long as the pump 14 is displacing fluid at a pressure above a minimum value through the outlet 48, the pressure switch 46 will be closed and the connection between the lever switch 42 and the counter means 18 will be completed. With each rotation of the cam 16, a fixed amount of fluid or chemical is transferred and the lever switch 42 is closed one time completing the circuit to the counter means 18 one time. As that circuit is completed, the slidable core 54 in the solenoid coil 52 will shift to index the indicator dial 56 and reduce the value indicated thereon by a tenth of a gallon. Should the fluid supply 114 become empty or the pump not create an outlet pipe 48 pressure above a minimum value, the conventional pressure sensitive switch 46 will not remain closed to complete the circuit from the counter cam 16 to the counter means 18 and the closing of the lever switch 42 will not cause the indicator dial 56 to be indexed. In this way, the indicator 20 will not be reduced whenever fluid is not pumped through the outlet 48.
When the readings on the preset indicator 20 have been reduced to zero, the reset switch 64 will open to thereby disconnect the power switch 60 and the first terminal 72 of the second relay 74. With this break in the circuit, no power will flow from the first terminal 72 of the second relay 74 through plate 122 to the second terminal 86 of the second relay 74 and through line 84 to the slidable coil terminal 82 of the second relay 74 to maintain the coil terminal 82 in a closed position. Accordingly, the coil plate 122 will become unlatched resulting in a cessation of current flow from the second terminal 86 of the second relay 74 to the coil terminal 90 of the first relay 36. Thereupon the slidable core plate 124 of the coil in the first relay 36 will unlatch disconnecting the circuit between the first terminal 34 of the first relay 36 and the second terminal 92 of the first relay 36 thereby stopping the current flow from the source line 32 to the motor 12.
The preferred embodiment utilizes a first 36 and second 74 relay in providing current from the power source 10 to the source control means 22 and motor 12. However, an alternate embodiment as shown in FIG. 3 utilizes only a single relay 128. While the current flowing to and through the reset switch 64 will be increased in this embodiment, shown in FIG. 5, a suitable switch could be substituted for the lower capacity reset switch 64 necessary in the first embodiment. However, to minimize the amperage load encountered in the reset switch 64 and to provide a control circuit having a lower cost and longer life, the second relay 74 is added in the preferred embodiment so that the full motor amperage flows only through it and to the motor.
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A portable transferring and metering apparatus is provided which permits quick and easy transfer of chemical fluids from one container to another without unnecessary exposure of the operator to chemicals being transferred. An adjustable metering device controls the transfer of a desired volume of chemicals and shuts down the transfer pump upon completed transfer of that volume of chemicals.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application Ser. No. 12/711,182, filed Feb. 23, 2010, which is a continuation of U.S. patent application Ser. No. 11/713,485, filed Mar. 2, 2007, which is a continuation of U.S. patent application Ser. No. 09/613,497, filed Jul. 11, 2000, now U.S. Pat. No. 7,316,672, which is a continuation of U.S. patent application Ser. No. 09/078,223, filed on May 13, 1998, now U.S. Pat. No. 6,142,982, which is a continuation of International Application No. PCT/GB96/02802, filed Nov. 14, 1996, which claims priority to British Patent Application No. GB9523253.4, filed Nov. 14, 1995. All of the above-mentioned applications are hereby incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates to the healing of wounds and, more particularly, to apparatus for stimulating the healing of superficial wounds.
[0004] 2. Description of Related Art
[0005] PCT Application No. GB95/01983 (WO 96/05873) describes apparatus for stimulating the healing of wounds comprising a porous pad which is permeable to fluids for introduction into the wound, a dressing for covering the wound and providing an air-tight seal around the wound, a drainage tube connecting the pad to a suction pump so that negative pressure can be applied to the wound to draw fluids therefrom, and a canister for collecting fluids sucked from the wound. The apparatus described in the above application has proved to be clinically effective but there are some limitations in its use.
[0006] The apparatus described in the above PCT application is effective for treating a wide variety of different types and sizes of wounds. However, it may require the patient to undergo treatment on the apparatus for a long period. In cases where the patient is confined to bed this may not be a major problem but where the patient is mobile it means that he or she would be confined for long periods while the treatment takes place.
SUMMARY
[0007] According to one aspect of the present invention there is provided a portable therapeutic apparatus for stimulating the healing of superficial wounds in a person, which comprises a housing containing a suction pump and a canister for containing fluids drawn from the wound by said pump, said canister including means for connection to a dressing in the region of the wound and a harness or belt for supporting the housing on the person.
[0008] Typically, the housing will have a curved surface on the side intended to be supported against the person's body so as to make the apparatus more comfortable to wear. In addition, controls and indicators indicating the status of the treatment being applied to the wound are preferably located on the supper side of the housing so that the patient can easily see, e.g. the level of suction pressure being applied and the program for such treatment.
[0009] The suction pump is conveniently driven by an electric motor and batteries for such motor being contained within the housing. However, it is generally more convenient to provide a separate housing for the batteries since these can be placed on the belt or harness in such a way as to balance the weight of the housing, preferably in a housing shaped similarly to the housing for the pump and canister.
[0010] The canister should be removably mounted within the housing, e.g. by means of a latch or similar release mechanism, so that the canister can be readily removed and replaced when full.
[0011] In a portable therapeutic apparatus (in contrast with a static apparatus of the kind described in the above PCT application which cannot be easily carried by the patient), it is less easy to determine the pressure prevailing at the wound site being treated. This is because the pressure will depend, in part, upon the hydrostatic height between the pump and the wound being treated and this height may vary during the treatment, depending upon the patient's movements. Apparatus in accordance with the invention overcomes this problem by providing an additional conduit connecting the wound site or an area close thereto to a pressure-detecting means, preferably located in the housing. The pressure-detecting means can be linked to a microprocessor programmed to maintain such pressure within a predetermined range irrespective of the movement of the patient. This can be done by, for example, signaling the pump to increase its speed where the hydrostatic pressure increases between the pump and the wound site or, conversely, reducing its speed where the hydrostatic pressure is reduced. This feature can also be used in a static therapeutic apparatus of the kind described in the above-mentioned application.
[0012] In the apparatus described in the above PCT application, the level of liquid in the canister is monitored by capacitance measurement. It has now been found that a simpler way of determining when the canister is filled is by measuring or detecting the pressure drop across the canister. The pressure drop can be increased by providing a filter barrier in the region of the outlet end of the canister.
[0013] Thus, when the liquid reaches a level within the canister so as to substantially occlude the filter, a sharp pressure change occurs in the conduit between the canister and the pump. By monitoring this pressure change, the point at which the canister is filled can be accurately determined.
[0014] Other features which are considered as characteristic for the invention are set forth in the appended claims.
[0015] Although the invention is illustrated and described herein as embodied in a wound treatment apparatus, it is nevertheless not intended to be limited to the details shown, since various modifications and structural changes may be made therein without departing from the spirit of the invention and within the scope and range of equivalents of the claims.
[0016] The construction and method of operation of the invention, however, together with additional objects and advantages thereof will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is a schematic layout of the apparatus in accordance with the invention,
[0018] FIG. 2A and B are pictorial representations of the housing of the pump and canister,
[0019] FIGS. 3A and B are pictorial representations of the apparatus supported on a belt and harness, respectively,
[0020] FIG. 4 is an exploded view of the housing showing the contents,
[0021] FIGS. 5A to 5F show various views of a preferred form of the canister and a section of a multi-lumen tube,
[0022] FIGS. 6A to 6D show various views of a foam dressing connector for connecting the housing to the dressing,
[0023] FIG. 6E shows a section of a modified multi-lumen tube, and
[0024] FIGS. 7A and 7B show a plan and perspective view of a surgical drape for use with the apparatus.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0025] Referring to the drawings, the portable therapeutic apparatus comprises a housing 210 (best shown in FIGS. 2A and 2B ), having rounded corners and a side 211 which is concavely curved in order to fit comfortably to the wearer's body.
[0026] The shaping of the housing with curved surfaces is to avoid sharp corners or edges which could dig in to the user or his career. The supper surface 212 is generally flat and has an LCD screen 213 on which details such as applied pressure can be displayed. Control buttons 214 are provided to adjust pressures and treatment intervals. Provision is made for housing a canister within the housing and a snap release cover 215 is arranged for removing or introducing the canister.
[0027] FIGS. 3A and 3B show schematically ways in which the housing 210 may be supported on the patient's body. In FIG. 3A the housing 210 is supported on a belt 216 and its weight is balanced by a similarly rounded casing 217 containing a rechargeable battery pack. FIG. 3B shows an alternative arrangement in which the housing is supported on a harness 218 and again a battery pack is contained in a housing 219 , also supported on the harness.
[0028] FIG. 4 shows an exploded view of the housing 210 indicating the main components within the housing. The housing consists of front and rear shell mouldings 1 and 2 having an external bet clip 21 for attachment to a belt or harness.
[0029] Within the housing shell 1 is located a suction pump 6 with associated electric motor 6 A and the pump is connected by a silicon rubber tube 103 to a canister spigot 7 A in a cavity 20 for the canister 100 . Also connected to a second canister spigot 7 B via a tube 10 is a pressure relief valve and both tubes 103 and 10 are connected via T-connectors T to pressure transducers (not shown). A microprocessor 4 is mounted on a PCB board S and a membrane assembly 3 incorporates an LCD indicator and control buttons.
[0030] The apparatus may include means for recording pressures and treatment conditions given to a particular patient which may be printed out subsequently by the physician. Alternatively, the equipment may include a modem and a telephone jack so that the conditions under which the patient has been treated can be interrogated by the physician from a distant station.
[0031] Canister 100 is a push fit into the cavity 20 and its lower end is supported in a cover 30 . The cover 30 incorporates fingers 31 which are releasably engageable with lips 32 to hold the canister in position. The canister and the latch mechanism is arranged so that when the latch is engaged, the spigots 7 A and 7 B are in sealing engagement or abutment with tubular protrusions 33 and 34 formed in the top of the canister.
[0032] The method of operation of the apparatus can be appreciated from the schematic layout in FIG. 1 , in which the canister 100 is connected via tube 101 to a porous dressing 102 at the wound site. Suction is applied to the wound site via the canister by a tube 103 , connected to the pump 6 . The pressure in the tube 103 is detected by the transducer 105 .
[0033] A second tube 106 is connected to the wound site 102 at one end, and also to a pressure relief valve 8 and to a second transducer 108 . Tubes 106 and 101 can be combined in a multi-partitioned tube in a manner to be described later. By means of tube 106 and transducer 108 the pressure at the wound site can be measured or monitored. A filter 109 is placed at or close to the outlet end of the canister 100 to prevent liquid or solid particles from entering the tube 103 . The filter is a bacterial filter which is hydrophobic and preferably also lypophobic.
[0034] Thus, aqueous and oily liquids will bead on the surface of the filter. During normal use there is sufficient air flow through the filter such that the pressure drop across the filter is not substantial.
[0035] As soon as the liquid in the canister reaches a level where the filter is occluded, a much increased negative pressure occurs in tube 103 and is detected by transducer 105 . Transducer 105 is connected to circuitry which interprets such a pressure change as a filled canister and signals this by means of a message on the LCD and/or buzzer that the canister requires replacement. It may also automatically shut off the working of the pump.
[0036] In the event that is desired to apply intermittent suction to the wound site, a pressure relief valve 8 enables the pressure at the wound site to be brought to atmospheric pressure rapidly. Thus, if the apparatus is programmed, for example, to relieve pressure at 10 minute intervals, at these intervals valve 8 will open for a specified period, allow the pressure to equalize at the wound site and then close to restore the suction. It will be appreciated that when the constant suction (or negative pressure) is being applied to the wound site, valve 8 remains closed and there is no leakage from atmosphere. In this state, it is possible to maintain negative pressure at the wound site without running the pump continuously, but only from time to time, to maintain a desired level of negative pressure (i.e. a desired pressure below atmospheric), which is detected by the transducer 105 . This saves power and enables the appliance to operate for long periods on its battery power supply.
[0037] Instead of running two separate tubes to the wound site, it is preferable to contain tubes 106 and 101 in a single tube which is connected through the canister.
[0038] Thus, for example, tubes 103 and 101 may comprise an internal tube surrounded by an annular space represented by tube 106 . This is illustrated in FIGS. 5A to 5F and in a modified form of FIG. 6E .
[0039] In an alternative embodiment, the multi-lumen tube may be constructed as shown in FIG. 6E . In this embodiment, the internal bore 606 comprises the line 101 (see FIG. 1 ) and is used to extract fluids from the wound site. Air flow (represented by line 106 in FIG. 1 ) passes down conduits 607 located within the walls of the tube. By spacing the conduits 607 at 90° intervals around the tube, the risk of arresting the air flow by kinking or twisting the multi-lumen tube is minimized.
[0040] FIG. 5E is a plan view of the top of a preferred shape of canister, the generally triangular shape in section being chosen to fit better the space within the cavity 20 (see FIG. 4 ). Tubular protrusions on the top of the canister are connected internally of the canister with respectively conduits 124 and 121 (see sectional view of FIG. 5B ), thus maintaining a separation between the tubes which are represented by lines 103 and 106 in FIG. 1 . At the base of the canister, a moulding 125 facilitates connection to a multi-partitioned tube 126 shown in FIG. 5F . Tube 126 has a central bore 127 which is sized to fit over a spigot 128 in moulding 125 . At the same time, the external wall of tube 126 seals against the inner wall 129 of moulding 125 . Thus, compartment 124 will connect with central bore 127 and the compartment 121 will connect with the annular spaces 130 of tube 126 . In this way, a conduit 130 corresponds with line 106 and central bore 127 with line 101 as shown in FIG. 1 .
[0041] The partitioned tube need not continue all the way to the wound site 102 , but can be connected to a short section of single bore tube close to the wound site.
[0042] In the event of an air leak in the dressing at the wound site 102 , this can be detected by both transducers 105 and 108 reading sufficient negative pressure for a specific time period and then triggering a leak alarm, i.e. a message on the LCD, preferably also with an audible warning.
[0043] Typically, the pump 6 is a diaphragm pump but other types of pumps and equivalent components to those specifically employed may be substituted.
[0044] FIGS. 6A-6D show various views of a connector for attaching the multi-lumen tube at the wound site. FIG. 7A and 7B show a plan and perspective view of a surgical drape for attaching the connector to a porous dressing at the wound site. The connector comprises a moulded plastics disc-like cup 601 having a centrally positioned spout 602 . The spout 602 is sized to accept, as a closely sliding fit, the end of a multi-lumen tube, e.g., of the kind shown in FIGS. 5F or 6 E.
[0045] In use, a porous dressing is cut to correspond with the extent of the wound and pressed onto the wound as shown in FIG. 10 of our above cited PCT application WO 96/05873. Instead of introducing the lumen into the foam dressing, the cup 601 is pressed onto the porous dressing and secured by a surgical drape. However, if desired, the end of the lumen can be passed into the spout and additionally pressed into the foam. A surgical drape such as shown in FIGS. 7A and 7B , can be used to secure the connector, lumen and dressing. The drape comprises a polyurethane film 701 coated on one side with a pressure-sensitive acrylic resin adhesive. A hole 702 is cut through all layers of the drape and the hole is dimensioned to correspond approximately with the outer cross-section of the spout 602 . Film 701 has an overall size which allows it to be adhered to the patient's skin around the wound site, while at the same time, securing the connector to the porous dressing. A sufficient overlap around the wound is provided so that an airtight cavity is formed around the wound.
[0046] In an alternative form, the drape can be made in two parts, e.g. by cutting along the line X-X in FIG. 7A . With this arrangement, the wound can be sealed by overlapping two pieces of surgical drape so that they overlap each other along a line Y-Y as shown in FIG. 6D .
[0047] The surgical drape may include a protective film 703 , e.g. of polyethylene, and a liner 704 which is stripped off prior to use to expose the pressure-sensitive adhesive layer. The polyurethane film may also include handling bars 705 , 706 , which are not coated with adhesive, to facilitate stretching of the film over the wound site. The dressing is preferably a pad of porous, flexible plastics foam, e.g. reticulated, open intercommunicating cellular flexible polyurethane foam, especially of the kind described in the above-mentioned PCT Application WO 96/05873.
[0048] Alternatively, a reticulated intercommunicating cellular foam made from flexible polyvinylacetate or polyvinylalcohol foam may be used. The latter is advantageous because it is hydrophilic. Other hydrophilic open celled foams may be used.
[0049] In another method of therapy, the foam dressing may be sutured into a wound after surgery and the foam dressing connected to the pump unit by the multi-lumen catheter. Negative pressure can then be applied continuously or intermittently for a period determined by the surgeon, e.g. from about 6 hours to 4 to 5 days. After this period, the dressing is removed and the wound re-sutured.
[0050] This therapy improves the rate of granulation and healing of wounds after surgery.
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A therapeutic apparatus for stimulating the healing of a wound site includes a polyurethane foam positioned at the wound site and a connector having a disc-like cup and an elbow-shaped spout. The connector is positioned in contact with the polyurethane foam, and the elbow-shaped spout is configured for connection to a tube that is capable of delivering negative pressure through the elbow-shaped spout and to the polyurethane foam. The therapeutic apparatus further includes a drape having a hole, the drape being positioned over the connector such that the elbow-shaped spout extends through the hole in the drape.
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BACKGROUND OF THE INVENTION
The invention relates to a child seat, in particular a child seat for a motor vehicle.
A multiplicity of children's seats are known. The most frequent are so-called bucket seats whose components, which comprise the seat part, backrest and head restraint, are assembled from half shells. Adapting the size to a growing child is allowed to some extent in that the distances of the shell parts from one another can be changed. However, the shell parts themselves are generally, as plastic parts, of rigid design and therefore only permit slight adaptation to the growing child. In the long term the seats are not comfortable and do not satisfy the orthopedic requirements. The child is held either by the child seat's own belt or by a seat belt of the vehicle seat on which the child seat has been placed. Although the second variant better transfers those forces which act upon the child into the vehicle in the event of a crash, smaller children, in particular, can only inadequately be held in the child seat in the event of slow movements because of the flexibility of the seat belt.
It is accordingly an object of the present invention to provide an improved child seat.
SUMMARY OF THE INVENTION
The above and other objects and advantages of the present invention are achieved by the provision of a child seat having a seat-surface structure connected to a back rest, wherein the seat-surface structure defines a seat surface having a length extending in a longitudinal direction. An adjustable portion of the seat-surface structure can be moved in substantially the longitudinal direction and secured relative to a second portion of the seat-surface structure that at least partially defines the seat surface.
The seat surface can be lengthened (or shortened) by virtue of the fact that one part of the seat-surface structure can be adjusted and secured in the longitudinal direction relative to those remaining parts of the seat-surface structure which define the seat surface. This enables adaptation to the continuing growth of the child, in particular from nine months to twelve years. The child is then able to hang his legs down comfortably over the end of the seat surface, while being securely supported, or place them on the seat surface, depending on the length of his legs. The adaptation can most simply be carried out on the child seat when it is not installed and can occasionally be changed depending on the growth rate of the child. In a preferred, simple design of an adjustable seat surface of this type, the adjustable part of the seat-surface structure is designed as a hoop which, guided by guide bushes, can be moved within a region of displacement, the guide bushes preferably being fastened to lateral parts of the child seat.
It is advantageous if a securing device is provided in the region of the seat surface, which securing device releasably secures the adjustable part of the seat-surface structure relative to the remaining parts thereof. A preferred, simple and, at the same time, stable structure results if the securing device releasably connects the hoop to at least one crosspiece running between two side parts of the seat-surface structure. The securing device can be attached at its front end by a socket to the hoop. With a plurality of ribs in its rear region for attaching it to the crosspiece, the securing device provides the option of securely holding the hoop, at different distances from the crosspiece.
In accordance with another aspect of the invention, the securing device can be pivoted about the hoop, with the socket as a bearing, so as to release the securing device. So that the securing device does not inadvertently become detached from the hoop or become wedged elsewhere, the pivoting region of the securing device is preferably restricted by means provided on the seat-surface structure and/or by means provided on the securing device. One such means can form the mat which is fixed in the seat-surface structure for the purpose of supporting the padding.
The securing device is advantageously designed at the same time as a ramp which rises from the rear to the front so that the child does not dive under the seat-belt in the event of the vehicle decelerating sharply.
An increase in seat comfort results from the inclination of the seat-surface structure being adjustable relative to the substructure. An adjustment of the inclination in a space-saving manner is possible if during the adjustment of the inclination the seat-surface structure is pivoted about a spatial shifting axis of rotation. This can be realized, for example, by the seat-surface structure having bearing bolts which are guided in slotted guides of the substructure. Alternatively, other guide parts could also be guided in corresponding slotted guide links.
In principle, numerous adjustments of the inclination are possible. However, for a simple and nevertheless comfortable design of the child seat it is sufficient for the seat-surface structure to be able to be secured in an essentially upright sitting position and an inclined sleeping position. In the case of the preferred design with bearing bolts it is possible, for example, for the securing to take place at least partially by the bearing bolts engaging into latching recesses of the slotted guides. In addition, a further securing in the sleeping and/or sitting position can take place by means of at least one pivotable latch which locks a bearing bolt in place. The preference for the upright sitting position because of the inherent weight of the child seat is possible if during the transfer from the sitting position into the sleeping position, the bearing bolts are moved obliquely upward into at least partially rising regions of the slotted guides, and the seat-surface structure is also raised as a result.
In order to obtain better sliding properties and to reduce the wear, the bearing bolts can be guided in separately formed sliding guides which function as the slotted guide, wherein the sliding guides are inserted into cutouts in the side walls of the substructure. The sliding guides are preferably made of a harder material than the side walls.
As a result of the fact that the backrest has a belt-retaining device which, in at least one operating mode, clamps a seatbelt in one pulling direction and releases it in the other pulling direction, the seatbelt can be fastened easily and securely on the child seat and can be removed again. With appropriate accessibility to the belt-retaining device it is also possible for the seatbelt to be introduced into the belt-retaining device without having to actuate the latter by hand.
The belt-retaining device advantageously has at least one pivotable, eccentrically mounted belt retainer with which the required asymmetry in both possible pulling directions is achieved. When the seatbelt bears against the belt retainer, it preferably carries along the latter in the event of being pulled. This is assisted if the belt retainer has increased friction at least over part of its outer surface. To improve the putting-on of the seatbelt, the belt retainer preferably has a rounded portion on its free end. Clamping is more simple if the belt retainer is spring-loaded in a pivoting direction and is pretensioned relative to a part of the belt-retaining device. In order to be able to fasten the child seat on the left or right on any vehicle seat, the belt-retaining device preferably has a respective belt retainer on the left and on the right side of the child seat.
In a second operating mode, which is preferably used for older children, the belt-retaining device loosely surrounds the seatbelt. This is advantageously achieved by the belt-retaining device having a pivotable projection which, when it bears against a part of the belt-retaining device, forms an annularly closed opening for the seatbelt. This projection may, for example, be provided on the free end of the belt retainer.
If the belt-retaining device has, as a supporting part, a hoop which is arranged on the backrest, this results in simple and cost-efficient production.
As an option for adapting the child seat to the growing child and to increase the safety and comfort, the child seat according to the invention can have a seat surface which can be changed in length, a changeable inclination and also a belt retainer. However, it can also be fitted with only one of these options or with any desired combination of two options.
A further option for adapting the child seat to the growing child results if lateral supports which can be adjusted and secured in height and/or width, i.e. in the distance from the seat surface or with respect to each other, are provided on the backrest. Lateral supports of this type not only retain the child in the event of a lateral impact but also while the child is sleeping. If a hoop is provided for the belt-retaining device, said hoop is preferably fastened to the supporting means of the lateral supports, i.e. in the event of there being an option for height adjustment it can likewise be simultaneously displaced in height.
For easy transport of a child seat which is not in use, for example in the trunk of the motor vehicle, it is advantageous if the backrest can be folded forward relative to the seat-surface structure.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention is explained in more detail with reference to three exemplary embodiments illustrated in the drawing, in which
FIG. 1 shows a perspective view of a first child seat according to the invention without the padding and covering,
FIG. 2 shows a perspective view of various components of a seat-surface structure of this first child seat,
FIG. 3 shows a section through a ramp according to the line III—III in FIG. 2,
FIG. 4 shows a perspective view of a second child seat according to the invention without padding and a covering,
FIG. 5 shows a perspective view of various components of a substructure of this second child seat,
FIG. 6 shows a side view of the left side wall of the substructure of this second child seat without a surround piece that cover the side wall,
FIG. 7 shows a side view of the left side part of the seat-surface structure of this second child seat,
FIG. 8 shows a perspective view of a third child seat according to the invention without padding and a covering,
FIG. 9 shows a perspective view of a hoop of the belt-retaining device of this third child seat,
FIG. 10 shows a partially cut-away view of a belt retainer of this third child seat with caps, springs and hoop,
FIG. 11 shows a plan view of the belt retainer in the direction of the arrow IV in FIG. 10,
FIG. 12 shows a section through the belt retainer along the line V—V in FIG. 11,
FIG. 13 shows a plan view of the lower cap in the direction of the arrow VI in FIG. 10 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
When installed a child seat is fastened on a motor-vehicle rear-seat bench. All of the following directional data are derived from the direction of travel of the motor vehicle in which the child seat is installed, and its normal alignment.
In the first exemplary embodiment, the child seat has a substructure 1 with which the child seat is supported on the seat surface of the rear-seat bench. A seat-surface structure 3 is arranged on the substructure 1 . The supporting means of a backrest 5 is arranged on the seat-surface structure 3 but could also be arranged on the substructure 1 . To the left and right of the seat-surface structure 3 are arranged armrests 7 which are preferably connected to the seat-surface structure 3 . The upper side of the seat-surface structure 3 , the front side of the backrest 5 and the upper and inner sides of the armrests 7 are padded, which is not illustrated in the drawing. The above-mentioned parts are also covered by material coverings which are likewise not illustrated.
The seat-surface structure 3 has a respective side part 8 on the left and right, which side part is preferably produced as a metallic punched and bent part. The two side parts 8 are of mirror-inverted design and are connected to one another via two crosspieces 10 to form a seat frame. The two crosspieces 10 are preferably designed as cylindrical tubes and are attached, preferably screwed or welded, in the lower region of the side parts 8 . To facilitate the attachment, the lower edge of the side part 8 is bent inward and then upward and is provided with two notches in which the crosspieces 10 are placed during assembly. That upper region of each side part 8 which is pulled forward and is partially bent outward simultaneously forms the support of the armrest 7 . On the outside each side part 8 is provided in the lower region with a tube 9 which is bent in a U shape, points downward and around which the covering of the armrest 7 is fixed downward.
The side part 8 is provided somewhat below its center with an inwardly pointing shoulder which runs in the longitudinal direction. The shoulder is formed in this case by two parts 8 ′ of the side part 8 , which parts first run downward, then run inward at a right angle and then again run downward at a right angle, and is also formed, in a sectionally alternating manner with the latter, by two further parts 8 ″ of the side part 8 which first run inward at a right angle and then run downward at a right angle. The parts 8 ′ and 8 ″, which are bent out in different ways, enclose in this case a channel which has a virtually square cross-section and is open to different sides.
This channel has inserted into it a guide bush 11 which is preferably made of plastic, is open to the front and rear and around its front opening has a bead which serves as a stop for the front part 8 ′ of the side part 8 when the guide bush 11 is inserted into the channel. On the lower side the guide bush 11 furthermore has a projection by which it engages, after the insertion, behind the rear part 8 ′ of the side part 8 and is thus secured against displacement. A hoop 13 , which is bent in a U shape and is made from a tube, preferably an aluminum tube, is introduced by a respective leg from the front into a guide bush 11 , those ends of the legs which project behind the guide bushes 11 being prevented from again being pulled forward by the guide bushes 11 by the insertion of a respective stopper with latching projections.
A ramp 15 , which is preferably made of plastic and rises slightly from the rear to the front, is designed such that it is mirror-symmetrical with respect to the longitudinal direction. On the upper side, approximately in the center, the ramp has a hump which later comes to lie between the legs of the child. At the front end, the ramp 15 is provided with a gripping portion 17 which is bent downward and runs in the transverse direction. The rear side of the gripping portion 17 and a single rib 19 which runs parallel to the latter and protrudes downward from the lower side of the ramp 15 , form a socket 21 which has a virtually U profile and is open downward. The ramp 15 is placed with the socket 21 onto that part of the hoop 13 which runs transversely, this part of the hoop 13 being lightly gripped behind by the gripping portion 17 and the single rib 19 in the manner of a clip connection.
On the lower side in its rear region the ramp 15 has a plurality of parallel ribs 23 between which are respectively defined downwardly open grooves having a semicircular profile. The ramp 15 is fitted in this rear region into the front crosspiece 10 , which runs between the two side parts 8 , in such a manner that the crosspiece 10 comes to lie between two ribs 23 . As a result, the ramp 15 acts as a securing device which releasably secures the hoop 13 relative to the fixed parts of the seat-surface structure 3 , in particular the side parts 8 . Depending on the arrangement of the ramp 15 in each case, the rear crosspiece 10 can likewise come to lie between two ribs 23 .
In the front region of the ramp 15 , the latter has, on the left and right side, two mirror-inverted lugs 27 which are of integral design with the ramp and first run in a J shape from the ramp 15 downward and then are bent outward. The lugs 27 are arranged with their ends underneath those parts of the hoop 13 which run to the rear. As long as the ramp 15 rests upon the crosspiece 10 , the lugs 27 bear against the hoop 13 with a slight pretension.
A mat 29 is arranged in the center of the seat-surface structure 3 above the ramp 15 . The mat 29 consists of rubber and textile parts connected to one another and is fastened under pretension on each side to the side parts 8 by three clips 31 . For the fastening into those regions of the parts 8 ″ which run downward, the side parts 8 have bent-out eyelets for the clips 31 , specifically, one eyelet in the front part 8 ″ and two eyelets in the rear part 8 ″.
Together with the front part of the ramp 15 , the mat 29 supports the padding for the seat surface, i.e. together with the side parts 8 and the hoop 13 it defines the seat surface. The covering for the seat surface is fastened behind the rear end of the mat 29 , for example on the rear crosspiece 10 , runs forward and downward over the gripping portion 17 and is then replaced by strips of rubber which are finally fastened again to the rear end of the covering via textile adhesive fastenings.
To change the length of the seat surface, the user releases the covering, grips the gripping portion 17 and pivots the ramp 15 a short distance upward around the hoop 13 as an axis, the socket 21 forming the bearing for the hoop 13 during the pivoting movement. The pivoting movement is restricted in that the rear end of the ramp 15 comes to bear against the lower side of the mat 29 . The ramp 13 is prevented from being inadvertently lifted off the hoop 13 by the lateral lugs 27 which bear under pretension against the hoop 13 . As the ramp 15 pivots upward, the ribs 23 are released from the crosspiece 10 .
If the ramp 15 is pivoted upward, the hoop 13 can be moved within the guide bushes 11 . The seat length results from the position of the hoop 13 in the longitudinal direction relative to the remaining parts of the seat-surface structure 3 . If the desired seat length is reached, the user pivots the ramp 15 downward again until the crosspiece 10 again comes between two ribs 23 , and the ramp 15 is thus again supported on the rear end. The covering is then pulled taut again and fastened.
The ramp 15 is prevented from inadvertently pivoting upward while the child seat is in use by the mat 29 during use being pressed downward, in the extreme case as far as the ramp 15 , with the result that the ramp 15 has no space available to undertake a pivoting movement, and furthermore by the lugs 27 bearing against the hoop.
In the second exemplary embodiment, the child seat has a substructure 1 with which the child seat is supported on the seat surface of the rear-seat bench. A seat-surface structure 3 is arranged on the substructure 1 . The supporting means of a backrest 5 is arranged on the seat-surface structure 3 but could also be arranged on the substructure 1 . To the left and right of the seat-surface structure 3 are arranged armrests 7 which are preferably connected to the seat-surface structure 3 , for example via side parts 8 . The upper side of the seat-surface structure 3 , the front side of the backrest 5 and the upper and inner sides of the armrests 7 are padded, which is not illustrated in the drawing. The abovementioned parts are also covered by material coverings which are likewise not illustrated.
The substructure 1 comprises a virtually square baseplate 70 which, to the left and right, is in each case provided with a side wall 72 which is of integral design with the baseplate 70 and is drawn upward. The baseplate 70 together with the side wall 72 is preferably made of plastic. For stability reasons the baseplate 70 is provided on the upper side with three flat, transversely extending ribs 70 ′ on whose lower side the baseplate 70 has corresponding depressions. In the front edge region in the baseplate 70 there is left open a gripping opening 70 ″ which serves for taking hold of the child seat.
The upper edge of each side wall 72 runs in the rear quarter approximately horizontally, then rises forwards at an angle of approximately 15° and then falls quickly down onto approximately a sixth of the length of the side wall 72 as far as the baseplate 70 . In the vicinity of the upper edge, the side wall 72 has two cutouts 72 ′ which penetrate the side wall 72 in the transverse direction, run in the longitudinal direction and at the same time rise slightly.
Inserted in the front of these cutouts 72 ′ is a front sliding guide 74 which is made of plastic, is designed in the manner of a shape formed from a closed band of constant width and on the inwardly pointing edge has a bead or shoulder as a stop for the insertion into the cutout 72 ′. When installed, the front sliding guide 74 has an elongated part which rises forward at an angle of approximately 10°, has parallel walls at the top and bottom and at the front is provided with an end section which points in the same direction and is rounded semi-cylindrically. At the rear end the front sliding guide 74 is provided with a latching recess 74 ′ which points downward away from the elongated part and is rounded approximately semi-cylindrically.
In the rear of these cutouts 72 ′ there is inserted a rear sliding guide 76 which is designed in the same manner as the front sliding guide 74 and is likewise made of plastic. When installed, the rear sliding guide 76 has an elongated part which has parallel walls at the top and bottom, is provided at the rear with an end section which points horizontally to the rear and is rounded semi-cylindrically, and in the rear the said part runs virtually horizontally and then rises forward at an angle of approximately 15°. At the front end the rear sliding guide 76 is provided with a latching recess 76 ′ which points downward away from the elongated part and is rounded approximately semi-cylindrically.
Four essentially cylindrical bearing bolts 78 are provided at one end with a flat, disc-shaped head 78 ′ of relatively large diameter and at the other end with a coaxial peg 78 ″ of smaller diameter than the remaining bearing bolts 78 . The horizontal bearing bolts 78 are pushed through the sliding guides 74 and 76 in such a manner that the head 78 ′ is arranged on the outside of the side wall 72 and thereby retains the associated bearing bolt 78 toward one side in the sliding guide 74 or 76 . By means of the pegs 78 ″ the bearing bolts 78 are fitted into holes 79 in the side parts 8 or, if they have a thread, are screwed in and are thereby protected toward the other side. The side parts 8 form supporting parts of the seat frame and, at the same time, of the seat-surface structure 3 . The outer surface of each side wall 72 is covered by a plastic surround 80 which is designed such that it fits and is preferably fastened to the side wall 72 via a clip connection.
The inclination of the upper parts of the child seat, i.e. the seat frame with the seat-surface structure 3 and the backrest 5 , can be changed relative to the substructure 1 . In an essentially upright sitting position of the child seat, the bearing bolts 78 are situated at the rear ends of the sliding guides 74 and 76 which are designed as slotted guides, the front bearing bolts 78 being arranged in the latching recess 74 ′ of the front sliding guides 74 and the sitting position being secured thereby, assisted by the inherent weight of the child seat.
Starting from this, the child seat is grasped at the seat-surface structure 3 and pulled forward and slightly upward. The front bearing bolts 78 , which are fastened to the side parts 8 of the seat-surface structure 3 , move out of the latching recesses 74 ′ and obliquely upward in the front sliding guide 74 which acts as a ramp. At the same time, the rear bearing bolts 78 move forward and slightly upward along the rear sliding guide 76 . The change in inclination does not involve a pivoting movement about a positionally fixed axis of rotation but rather an imaginary pivoting movement about an imaginary, horizontal, transversely running axis of rotation which moves downward and slightly forward during the change in inclination so that the child seat does not have to be removed from the rear-seat bench for the change in inclination. As soon as the bearing bolts 78 arrive at the front ends of the bearing guides 74 and 76 , the rear bearing bolt 78 can engage into the rear latching recess 76 ′ because of the inherent weight of the child seat. The sleeping position is thereby reached.
In order additionally to secure the sleeping position, a latch 82 is provided, for example, on the left side of the substructure 1 , which latch can be pivoted about a horizontal axis of rotation which runs parallel to the bearing bolts 78 and below the rear latching recess 76 ′. The latch 82 is mounted in the side wall 72 , is arranged between the latter and the surround 80 and is opened rearward. The dimensions of the latch 82 are selected in such a manner that it can slightly engage around the head 78 ′ of the left, rear bearing bolt 78 from above, if it is in the rear latching recess 76 ′, and thereby lock it in place. The latch 82 can be spring-loaded toward the securing position and can be pressed on or pulled on by means of a lever or a Bowden cable. It can also be designed in a manner such that, when the seat-surface structure 3 is grasped, the latch is at the same time pivoted back for the transfer into the sitting position.
A corresponding latch can be provided for the additional securing of the sitting position, in order, for example, on the opposite side of the child seat to lock the right, front bearing bolt 78 in place when it engages into the front latching recess 74 ′.
In the third exemplary embodiment, the child seat has a substructure 1 with which the child seat is supported on the seat surface of the rear-seat bench. A seat-surface structure 3 is arranged on the substructure 1 . The supporting means of a backrest 5 is arranged on the seat-surface structure 3 but could also be arranged on the substructure 1 . To the left and right of the seat-surface structure 3 are arranged armrests 7 which are preferably connected to the seat-surface structure 3 , for example via side parts 8 (FIGS. 1, 2 , 4 and 7 ). The upper side of the seat-surface structure 3 , the front side of the backrest 5 and the upper and inner sides of the armrests 7 are padded, which is not illustrated in the drawing. The abovementioned parts are also covered by material coverings which are likewise not illustrated.
A belt-retaining device 85 is arranged on the backrest 5 . The belt-retaining device 85 has a hoop 87 which consists, for example, of a steel tube of 8 mm diameter with 1 mm wall thickness. The hoop 87 is fastened to a supporting means 44 for lateral supports 42 , 43 of the child seat, the supporting means 44 being displaceable in turn relative to the backrest 5 and being securable on the latter. The hoop 87 is bent to the left and right in a mirror-inverted manner. From the center, the hoop 87 initially runs transversely to the child seat, then downward, obliquely forward and again upward, in order to form a holder for the supporting means 44 . After approximately two thirds of its height the hoop 87 runs to the rear, outward, and again forward in order to loop around a backrest strut 33 of the backrest 5 . The hoop 87 then runs upward in a section 87 ′, bends around with an alignment obliquely forward and then in an end section runs downward again in order to end in front of that section which loops around the backrest strut 33 . Somewhat above its two ends a small plate 88 is pushed onto the hoop 87 and fastened, preferably welded, the plate bearing, toward the outside of the seat, a downwardly pointing tooth 88 ′.
As a further part of the belt-retaining device 85 a respective belt retainer 90 of cylindrical design is pushed from below onto the end section of the hoop 87 and secured by a spring mechanism described later. Each end section of the hoop 87 is surrounded by a holder 91 of the belt retainer 90 and, at least over part of its length, supports the belt retainer 90 . In this case, the holder 91 runs between the two end surfaces and parallel to the central axis of the belt retainer 90 so that the belt retainer 90 is thus mounted eccentrically. On the outside of its circumferential surface, the belt retainer 90 has a rubber coating for increasing the friction, and otherwise is made of plastic.
From the lower end side of the belt retainer 90 a lower spring 92 is introduced into the holder 91 , wound around the hoop 87 and supported at its upper end on a shoulder of the holder 91 . The lower end of the lower spring 92 is supported on the hoop 87 , for example, on a spring ring which is seated in an annular groove at the end of the hoop 87 . The lower spring 92 is pretensioned in the axial direction, in this manner downwardly secures the belt retainer 90 and presses it against the plate 88 .
A lower cap 94 having essentially the basic shape of a half lens is provided on the flat side with three pin-like spikes which are introduced with frictional engagement into corresponding blind holes or other recesses on the lower end side of the belt retainer 90 . The lower end side of the belt retainer 90 is covered thereby. The lower cap 94 at the same time forms the free end of the belt retainer 90 . On the side the lower cap 94 bears a projection 94 ′ which, as seen from the central axis of the belt retainer 90 , is offset relative to the holder 91 by approximately 30° in the circumferential direction.
From the upper end side of the belt retainer 90 an upper spring 96 is introduced into the holder 91 , wound around the hoop 87 and on its lower end supported in a longitudinal groove in the holder 91 . The upper end of the upper spring 96 is supported on the hoop 87 , preferably on the plate 88 or its tooth 88 ′. The upper spring 96 is pretensioned in the circumferential direction and thus attempts to pivot the belt retainer 90 about the hoop 87 . The distance between the holder 91 and that parallel line which is furthest away therefrom on the outside of the belt retainer 90 is greater than the distance between the end section of the hoop 87 and that section 87 ′ of the hoop 87 which is situated in front of it. It is therefore not possible for the belt retainer 90 to be pivoted over the entire angular range because of the eccentricity, and the upper spring 96 attempts to bring the belt retainer 90 to bear against the section 87 ′ of the hoop 87 , to be precise, from the rear side of the child seat inward.
An upper cap 98 likewise with a half lens as the basic shape is placed onto the plate 88 and the upper end side of the belt retainer 90 and is fastened by two spikes placed into the belt retainer 90 . The upper cap 98 which is made of plastic has a lateral slot and thereby surrounds the hoop 87 .
The belt-retaining device 85 can be used in two different operating modes. In one operating mode use is made of the action just described of the upper spring 96 and of the eccentricity. In particular for smaller children, the normal three-point seatbelt of the rear-seat bench is advanced forward on the appropriate side of the child seat onto the lower cap 94 with a slight pull to the rear and upward. Because of the rounding of the cap 94 , the seatbelt slips onto the belt retainer 90 , remains attached to its rubber coating and carries along the belt retainer 90 counter to the force of the upper spring 96 . The belt retainer 90 is detached from the section 87 ′ of the hoop 87 in such a manner that a gap opens in between into which the seatbelt slides. If the seatbelt is released, the force of the upper spring 96 ensures that the belt retainer 90 pivots back again and clamps the seatbelt. If the child moves forward, the belt thus pulls forward and the clamping action increases so that the child is securely held in the child seat. The seatbelt can be put on using just one hand without the belt retainer 90 having to be grasped by the other hand.
In the other operating mode, use is made of the projection 94 ′. In particular for older children having more need of movement, the seatbelt, as just described, is first brought between the belt retainer 90 and the section 87 ′ of the hoop 87 . The belt retainer 90 is then pulled somewhat downward counter to the force of the lower spring 92 and pivoted until the projection 94 ′ comes to bear against the section 87 ′ of the hoop 87 . Because of the eccentricity, there then exists between the belt retainer 90 and the section 87 ′ of the hoop 87 a gap in which the seatbelt is situated. The gap is then closed upward and downward but laterally opened so that the seatbelt is surrounded, in this opening formed as a result, annularly and loosely by the hoop 87 , the belt retainer 90 and the lower cap with the projection 94 ′. The belt retainer 90 is then released to such an extent that the lower spring 92 can press it upward. As it does so, the tooth 88 ′ of the plate 88 engages into a recess on the upper end side of the belt retainer 90 . This prevents a possible pivoting movement, caused by the force of the upper spring 96 , of the belt retainer 90 . The loosely inserted seatbelt is prevented by the projection 94 ′ from sliding downward and from slipping out of the belt-retaining device 85 . However, the child can move comfortably. On the other hand, the belt-retaining device 85 in no way obstructs the seatbelt in the event of being subjected to stress, for example, in the event of a crash.
By renewed pulling of the belt retainer 90 downward, the tooth 88 ′ can again be brought out of engagement with the belt retainer 90 , with the result that the upper spring is again effective and can again be transferred to the first operating mode.
In a modified embodiment, because of the material and shape of the hoop 87 , the end section of the hoop 87 can be bent up elastically to a small extent. During the transfer to the second operating mode, the belt retainer 90 can thus be moved away somewhat from the section 87 ′ of the hoop 87 . The projection 94 ′ can then be guided past this section 87 ′ so that when the belt retainer 90 is released, the projection 94 ′ on the rear side of the section 87 ′ comes to bear against the section 87 ′ and is held in this position by the upper spring 96 . The lower spring 92 and the tooth 88 ′ are omitted in this embodiment.
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A child seat, in particular for a motor vehicle, has a seat-surface structure, which extends generally in a longitudinal direction and defines the seat surface, and a backrest. One part of the seat-surface structure can be adjusted and secured in the longitudinal direction relative to those remaining parts of the seat-surface structure which define the seat surface. A substructure that carries the seat-surface structure is operative so that the inclination of the seat-surface structure can be adjusted relative to the substructure. A belt-retaining device is carried by the backrest and operative in one operating mode to clamp the seatbelt, in response to the seatbelt traveling in a first pulling direction, and to release the seatbelt, in response to the seatbelt traveling in a second pulling direction. In another operating mode, the belt-retaining device loosely surrounds the seatbelt.
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CROSS-REFERENCE TO RELATED APPLICATIONS AND CLAIM TO PRIORITY
[0001] The present application claims the benefit of U.S. provisional patent application serial No. 60/290,342, filed May 14, 2001, the disclosure of which is incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention is directed to a method and apparatus for buffering a flow of stacks of objects, and more specifically, toward a method and apparatus for receiving a first number of stacks of discrete planar objects, such as frozen hamburger patties, from a stacking machine and presenting a second number of those stacks to a packing machine, especially when the first and second numbers are unequal.
BACKGROUND OF THE INVENTION
[0003] Frozen hamburgers, chicken patties, sausage patties, and other disk-like food products typically are prepared by a manufacturer on one piece of equipment and then fed into a freezer. After leaving the freezer, they are screened by a metal detector, which detects contaminated patties, and then conveyed to a stacker. The stacker forms the patties into one or more stacks, and the finished stacks are then placed in cases. Because the stacks formed by some stackers can vary in height, and because the number of stacks formed simultaneously by a stacker may be greater than the number of stacks that will fit in a row in a case, the finished stacks are often removed from the stacker and loaded into cases by hand. This manual loading step is labor-intensive, and, due to the presence of a human element, highly variable.
[0004] The problem of forming uniform stacks of patties is addressed by the novel stacking machine disclosed in the co-pending application entitled “Method and Apparatus for Stacking Discrete Planar Objects” filed concurrently herewith and assigned to the assignee hereof. The disclosure of that application is hereby incorporated by reference. However, as with many prior art devices, the subject stacker simultaneously forms more stacks than will fit in one row of a typical case. For example, in a preferred embodiment, the subject stacker receives four rows of frozen patties from a conveyor belt and simultaneously forms four stacks of patties. Cases of patties, however, can often accommodate only three stacks of patties per row, or possibly five stacks or more.
[0005] This problem could be addressed by adjusting the stacking machine to form only three stacks of patties at a time, but the reduction from four rows to three rows represents a twenty-five percent decrease in efficiency. Human packers can also address this problem by packing stacks one at a time and positioning each stack as required in a given case. However, as mentioned above, it would be desirable to fully automate the stacking and packing processes to provide greater consistency and to reduce costs.
[0006] In addition, not all cases are packed in the same manner. Some cases may hold only two rows of patties, for example, and it would be useful to have a machine that could be rapidly adjusted to convert four incoming rows of stacks into two outgoing stacks, depending on the product being packaged, or even to accommodate cases that alternate between two stacks per row and three stacks per row. Ideally, the change would be software controlled or require no more than the push of button to make. And, while reducing the number of rows is the general problem faced by the industry, under some circumstances it may be desirable to present more stacks to a packing machine than are provided at one time by a stacker—for example, if the stacker forms four rows of stacks at a time and a certain case requires six stacks in a row. Finally, the machine should be able to function under conditions where the number of incoming rows is equal to the number of outgoing rows and to do so in an efficient manner.
SUMMARY OF THE INVENTION
[0007] These and other difficulties are addressed by the present invention which comprises a novel buffering device that receives a first plurality of stacks of objects from a stacking machine and presents a second number of stacks to a packing machine for removal, where the second number may be greater than, less than, or equal to the first number. The invention includes a plurality of trays or similar receptacles sized and shaped to accommodate the stacked objects, which receptacles are mounted on carriers that can be moved between a first location where the stacks are received from a loading device and a second location where the stacks are removed by an unloading device.
[0008] In a preferred embodiment, the invention comprises a carousel around which a belt rotates continuously in a path having two generally parallel linear sections connected by curved portions. Each carrier is attached to the belt by a clamp which engages the belt in a jaw-like manner on opposites sides thereof. The clamp is attached tightly enough to cause the receptacle to move with the belt when the path of the carrier is unobstructed, but loosely enough that the belt will slide through the clamp when the path of the carrier is blocked. In this manner, the position of the carriers can be controlled somewhat independently of the positions of the other carriers without the need to provide separate controllers for the clamps on each carrier.
[0009] The movement of the receptacles is controlled so that a first number of receptacles is always available when needed to receive a first number of incoming stacks at a first location. The receptacles are then released to a second location from which the stacks are removed in groups of a second number. When the second number is less than the first number, the stacks must be removed at a rate greater than the rate at which the stacks of patties arrive at the carousel, and full carriers are buffered at a location between the first and second locations. When the second number of carriers is greater than the first number, the full carriers are accumulated at the second location until a second number of carriers is present. When the first and second numbers are the same, the carries merely move around the carousel in equally sized groups. While such a buffer can be incorporated into a stacking or packing machine, in the preferred embodiment, it comprises a stand-alone device that is connected between a stacker and a packer, thus allowing greater flexibility for use with different types stacking and packing machines.
[0010] In a preferred embodiment, the device further includes sensors for detecting the presence of carriers at different points around the carousel. A proximity sensor mounted near the path of the carriers detects the carriers as they pass. The sensors are operably connected to stops that block the passage of carriers when the stops are in an extended or in a blocking position. Because the carriers are somewhat loosely connected to the drive belt, the drive belt continues to move through the clamp when a carrier is blocked. Other carriers being moved by the belt engage the stopped carrier, and are likewise stopped. When the stop is moved to a releasing position, the carriers that were blocked begin again to move with the belt. A controller connected to the stops controls them so that so that carriers are released from the first stop in groups of a first number and released from the second stop in groups of a second number, where the first number can be greater than, less than or equal to the second number. Alternately, additional sensors can be used to determine whether the carriers are full or empty. When additional sensors are used, the controller releases only full carriers from the first location, and releases only empty carriers from the second location. Thus, with either embodiment, empty carriers are stopped at the first location and filled with stacks of frozen hamburger patties. When the carriers are full, the controller releases the stop to allow the filled group of carriers to pass and the next empty carrier is stopped. The full carriers travel around the carousel until they reach the second stop, which moves into the blocking position to keep the full carriers from passing. The full carriers remain at this location until stacks are removed by a stack transfer mechanism, and empty carriers are then released to travel back to the first location.
[0011] In the preferred embodiment, the number of carriers is related to the maximum number of incoming or outgoing rows of patties in a certain way to minimize the number of carriers needed, and this reduces the amount of space occupied by the machine. Applicant has found, for example, that a buffer for use between a stacking machine that produces four rows of patties and a packaging machine that requires three rows of patties as input, needs eleven carriers. By limiting the number of carriers, the width of the buffer can be kept small and the resulting buffer need not be much greater than the width of the stacking machine.
[0012] It is therefore a principal object of the invention to provide an apparatus for receiving a first number of stacks of objects at an input location and presenting a second number of stacks of objects at an output location.
[0013] It is another object of the invention to provide a method of buffering the flow of stacks of objects between a stacking machine and a packing machine.
[0014] It is a further object of the invention to provide an apparatus for matching the output rate of a first machine to the input rate of a second machine.
[0015] It is still another object of the invention to provide a carousel having a plurality of selectively positionable receptacles for receiving a plurality of stacks from a first machine and presenting a plurality of stacks to a second machine.
[0016] It is still a further object of the present invention to provide a free-standing stack transfer device that receives a first number of stacks of objects at a first location and presents a second, smaller number of stacks of objects at a second location.
[0017] It is yet another object of the present invention to provide a free-standing stack transfer device that receives a first number of stacks of objects at a first location and presents a second, larger number of stacks of objects at a second location.
[0018] It is yet a further object of the present invention to provide a buffer device that can be configured to accommodate different numbers of incoming stacks and differing numbers of outgoing stacks.
[0019] In furtherance of these objects, a method for buffering a flow of stacks of objects from a first location presenting a first number of stacks to a second location adapted to receive a second number of stacks is provided that includes the steps of providing a frame between the first location and the second location which frame has a first position and a second position. A plurality of carriers each adapted to hold a single stack is associated with the frame and a first number of carriers are moved to the first position. The first number of stacks are transferred from the first location to the first number of carriers at the first position, and then the first number of filled carriers at the first position are moved toward the second position. Whenever at least a second number of filled carriers are present at the second location, the stacks from the second number of filled carriers at the second position are removed to the second location. Lastly, empty carriers are returned from the second position toward the first position.
[0020] Another aspect of the invention comprises a system for buffering a flow of stacks between a first location and a second location that includes a frame having a first position with an exit end proximate the first location and a second position with an exit end proximate the second location and a drive. A plurality of carriers is supported by the frame and connected to the drive. The device further includes a first stop at the first position exit end, a second stop at the second position exit end, and a controller for actuating the first stop to allow carriers to pass the first location exit end in groups of a first number and for actuating the second stop to allow carriers to pass the second location exit end in groups of a second number.
[0021] A further aspect of the invention involves a method for receiving a first number of stacks of discrete objects from a stacking machine and presenting a second number of the received stacks for removal by a stack transfer machine. The method requires a frame having a periphery, a first location on the periphery, and a second location on the periphery, and a drive on the frame. A plurality of carriers adapted to hold a single stack are mounted on the frame and connected to the drive. A first sensor is provided for counting the number of carriers passing a first point and a second sensor is provided for counting the number of carriers passing a second point. A first stop is provided near the first point for preventing empty carriers from passing the first stop, and one stack is received in each of the first number of carriers at the first location. The first number of carriers are released from the first stop, but stopped at a second location by a second stop near the second point that prevents carriers from passing the second location. A second number of stacks is removed from the first number of carriers at the second location, and the second number of carriers are released by the second stop and moved toward the first location.
[0022] Yet another aspect of the invention comprises a buffer including a support frame, a platform having a periphery mounted on the support frame, and a guide extending around the periphery. A drive belt is mounted adjacent the platform along the periphery, and a drive is operatively coupled to the drive belt. A plurality of carriers is supported by the platform, each including a first member engaging the guide and a second member engaging the drive belt such that movement of the drive belt moves the carriers about the periphery of the platform. A first sensor is mounted at a first location for counting the number of carriers passing the first location, and at least one stop is provided that can be shifted between a first position in a path of travel of the carriers around the platform and a second position outside the path of travel of the carriers around the platform. A controller operatively coupled to the first sensor controls the position of the at least one stop.
[0023] A further aspect of the invention comprises a carrier having a trolley adapted to support a tray for holding stacks of objects. The trolley has a body with a first side and a second side and includes a first wall portion having an end and a second wall portion extending from the end of the first wall portion at an obtuse angle. An axle extends from the first side of the second wall portion and a wheel is rotatably supported by the second wall portion axle. A clamp is mounted on the first side of the first wall portion.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] These and other objects of the invention will become apparent from a reading and understanding of the following detailed description of the invention together with the following drawings of which:
[0025] [0025]FIG. 1 is a perspective view of a carousel buffer device having a plurality of trays supported on carriers according to the present invention.
[0026] [0026]FIG. 2 is an assembly drawing of a portion of the buffer device of FIG. 1 with the carriers and trays removed.
[0027] [0027]FIG. 3 is a side elevational view of one of the carriers shown in FIG. 1.
[0028] [0028]FIG. 4 is a rear elevational view of the carrier of FIG. 3.
[0029] [0029]FIG. 5 is a side elevational view of the buffer of FIG. 1.
[0030] [0030]FIG. 6 is a side elevational view of the buffer of FIG. 1 showing a stop for preventing the movement of the carriers in a non-engaged position.
[0031] [0031]FIG. 7 is a side elevational view of the buffer and stop of FIG. 6 showing the stop in an engaged position.
[0032] [0032]FIGS. 8 a - h are top plan views of the buffer of FIG. 1 showing the locations of full and empty trays around the periphery of the buffer as the buffer is used according to the method of the present invention.
[0033] [0033]FIG. 9 is a top plan view of the buffer device with the trays removed to show the positions of several sensors.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0034] Referring now to the drawings, wherein the showings are for purposes of illustrating a preferred embodiment of the invention only, and not for the purpose of limiting same, FIGS. 1 and 2 illustrate a buffer device designated generally by the numeral 10 which includes a frame 12 , a drive 14 and a plurality of carriers 16 supported by the frame 12 . Frame 12 includes vertical support portions 18 adapted to support the frame on a horizontal support surface, a generally planar upper support portion 20 that includes first and second openings 22 , and a motor support 24 mounted beneath upper planar portion 20 .
[0035] Drive 14 includes a motor 26 mounted on motor support 24 and operably connected to a drive gear 28 which turns a continuous drive belt 30 about a plurality of flanged wheels, including a first wheel 32 and a second wheel 34 . First and second wheels 32 and 34 each include a center opening 36 having a notch 38 for receiving a splined shaft. Two splined shafts 40 extend from center openings 36 upwardly through first and second openings 22 in the frame upper support 20 .
[0036] A bottom plate 42 having first and second openings 44 , as best shown in FIG. 5, a peripheral edge 46 and a raised rail 48 running around the peripheral edge is mounted on frame upper support 20 with first and second openings 44 aligned with openings 22 in the frame upper support 20 so that splined shafts 40 extend though these openings. Wheels 50 , as best shown in FIG. 2, are mounted on each of the splined shafts which wheels include center openings 52 shaped to receive shafts 40 and peripheral grooves 54 for receiving and holding a drive belt 56 . The drive belt 56 preferably has a circular cross section and is formed from a flexible, wear-resistant material, such as urethane.
[0037] A top plate 58 having first and second openings 60 , a peripheral edge 62 and a raised rail 64 running around the peripheral edge is mounted over bottom plate 42 and spaced apart therefrom by spacers 66 , with openings 58 positioned to receive splined shafts 40 . Bearings 68 are mounted on top plate 56 to rotatably secure the ends of shafts 40 . Thus, motor 26 turns drive gear 28 and causes drive belt 30 to move about first wheel 32 and second wheel 34 , which in turn causes splined shafts 40 and wheels 50 mounted thereon to rotate and drive drive belt 56 about a continuous path between bottom plate 42 and top plate 58 . Drive belt 56 preferably has a diameter greater than the width of peripheral grooves 54 , so that the belt only contacts the wheels about a small portion, less than 180 degrees, of the belt's circumference.
[0038] [0038]FIG. 1 illustrates a plurality of carriers 16 mounted on the top and bottom plates which carriers comprise trays 70 supported by trolleys 72 as best shown in FIGS. 2 - 4 . Each tray 70 includes a bottom wall 74 having a centrally located slot 76 with a slot edge 78 , a rear wall 80 and sidewalls 82 . The trays 70 are preferably mounted on the trolleys 72 in a manner that allows for easy removal thereof, so that appropriately sized trays 70 can be used for the objects being processed. Each trolley 72 , shown in more detail in FIGS. 3 and 4, includes a body portion 86 having a lower portion 88 with a lower end 90 and an upper portion 92 angled with respect to the lower portion 88 . A wall 94 projects from body lower portion 88 in the same direction as the angle of the upper portion, and includes a small wall 96 projecting from its end in the direction of angled upper portion 92 . A boss 98 is mounted on upper portion 92 and supports a shaft 100 on which a wheel 102 having a V-shaped peripheral notch 104 is rotatably mounted and held in place by a retainer 106 . A wheel support 107 is connected to wall 94 , and small wall 96 supports two shafts 108 on which first and second guide wheels 110 are mounted for rotation about axes parallel to lower portion 88 of body portion 86 . Projections 112 extending from the lower side of wall 94 support two additional guide wheels 114 , which guide wheels are mounted for rotation about axes normal to body lower portion 88 . Guide wheels 115 are also mounted on the bottom side of wall 94 , with axes parallel to body portion 88 and between guide wheels 114 and body portion 88 .
[0039] A clamp 116 is mounted on body lower portion 88 between guide wheels 110 and 110 notched wheel 102 , and includes an upper clamp member 118 pivotably supported on lower body portion 88 by a shaft 120 , and a lower clamp member 122 pivotably supported on a shaft 124 extending between lower body portion 88 and small wall 96 . Both the upper and lower clamp members are coated with, or preferably formed from, a low-friction, wear resistant material, such as UHMW polyurethane. The angular relationship between the upper and lower clamp members, and hence the distance separating the ends of the clamp members, can be adjusted by pivoting the upper clamp member and fixing it in place with fastener 126 .
[0040] The mounting of carriers 16 on the upper and lower plates is best shown in FIG. 5, wherein trays 70 are detachably connected to trolleys 72 , and the trolleys are arranged such that notch 104 of wheel 102 on the angled upper portion 92 of the trolley fits over an edge of raised rail 64 on the periphery of top plate 58 , guide wheels 110 engage the inner edge of raised rail 48 on bottom plate 42 , guide wheels 115 engage the outer edge of raised rail 48 , and guide wheels 114 engage the underside of bottom plate 42 .
[0041] The upper and lower members 118 and 122 , respectively, of clamp 116 are attached to drive belt 56 by placing the belt between the members and clamping the upper member in place so that a small force is exerted against the belt by the clamp members. The force must be great enough that friction between the clamp 116 and the belt 56 will keep the trolleys 72 fixed with respect to the belt when the path of the trolleys 72 is clear. The force also must be small enough that the frictional force between the belt 56 and the clamp 116 can be overcome by the drive motor to cause the belt to slip through the clamp when movement of one or more of the trolleys 72 is blocked by a stop.
[0042] A first solenoid-actuated stop 128 is mounted on frame 12 with a trolley-engaging portion 130 shiftable between a first, release position, shown in FIG. 6, below the lower ends 90 of the trolley bottom portions 88 and a second, stop, position, shown in FIG. 7, where the trolley engaging portion 130 blocks a path of the trolley 72 by forming a stop against which the lower ends 90 of the trolleys impact when the stop 128 is in its stopping position. A second, separately controllable, solenoid-actuated stop 134 is provided on the other side of the buffer device.
[0043] The shifting of the stops between stopping and releasing positions is controlled by a controller 136 , operably coupled to sensors 132 and 133 mounted on frame 12 below the tray bottom walls 94 , as best shown in FIGS. 5 and 9. These sensors are used to count the number of trays passing thereby. The controller 136 monitors the number of trays 70 passing over each of the sensors 132 or 133 , and causes the first stop 128 to shift to its stop position when a predetermined number of trays has passed. For example, when the buffer receives four stacks of patties at a time from a stacker, the trays 70 will be released in groups of four. Similarly, when stacks are removed in groups of three, the controller 136 shifts the second stop 134 into the blocking position and only allows the trays 70 to pass in groups of three. The operation of the stops 128 and 134 is coordinated with the operation of the stacker and stack transfer mechanism so that, in the embodiment described herein, at least four empty trays are always available to receive incoming stacks of patties and that at least three stacks of patties are present at the second stop 134 to be removed by a stack transfer device. An optical sensor 135 is also provided for detecting patties on the trays as they approach the loading position. Since these trays 70 should all be empty, an alarm occurs or the system shuts down when full trays are seen approaching the loading position.
[0044] As best shown in FIG. 9, two additional sensors 144 and 146 are also provided to help ensure that enough trays 70 are present upstream of stop 128 to receive incoming stacks of patties and that the correct number of stacks of patties are available for removal by a stack transfer device. Thus, for example, as sensor 128 is counting the passage of four trays 70 , sensor 144 upstream of sensor 128 is counting the passage of empty trays toward sensor 132 and stop 128 . Controller 136 is preferable coupled to the controller for a transfer device that brings stacks of patties to the buffer device 10 and configured so that stacks of patties will not be transferred to buffer device 10 until sensor 144 has detected the passage of four trays 70 . Thus, in the event that a problem arises that prevents four empty trays from lining up behind stop 128 , the transfer device will not attempt to transfer stacks of patties to the buffer device 10 . This reduces the likelihood that patties will be dropped or otherwise mishandled during processing. In a similar manner, sensor 146 counts trays 70 approaching sensor 133 , and as sensor 133 is counting the release of three empty trays 70 , for example, sensor 146 is counting approaching trays to ensure that at least three full trays are present at stop 134 and that at least three stacks are available for removal. Controller 136 is preferably connected to the controller for the downstream stack transfer device and prevents stacks from being removed from the trays stopped at stop 134 until three stacks are present for removal. The number of stacks arriving at and leaving the buffer device 10 can be varied, and the position of sensors 144 , 146 is adjustable so that these sensors can be placed near the location where the last of a given group of trays 70 will be found when the system is operating properly.
[0045] In a second embodiment, sensors 132 and 133 are used both to count the number of trays passing thereby and to detect whether the tray adjacent the sensor is full or empty, based upon whether slot 76 is blocked. The controller 136 monitors the status of the trays 70 passing over each of the sensors, and causes the first stop to shift to its stop position whenever an empty tray is detected and to shift to its release position when a full tray is detected. Similarly, controller shifts the second stop into the blocking position when a full tray is detected by sensor 133 and into the releasing position when actuated in an opposite manner, that is, set to prevent the passage of full trays while allowing empty trays to pass.
[0046] In operation, motor 26 drives drive belt 30 , turning first and second wheels 32 , 34 and rotating shafts 40 and wheels 52 mounted thereon. This in turn causes drive belt 56 to move continuously about the periphery of the buffer between plates 42 and 58 . The carrier trolleys 72 are clamped to belt 56 tightly enough that they are pulled about the peripheries of the upper and lower plates by the movement of the belt. The trolleys are guided by the engagement of trolley wheels 102 with upper plate raised rail 64 and the engagement of guide wheels 110 , 112 and 114 with the peripheral portion 46 of lower plate 42 . Stops 128 and 134 are selectively moved into and out of the path of travel of the trolleys and, when positioned in a stopping position, prevent trolleys from moving past the stops. The motor 26 continues to operate at a continuous speed, however, sliding belt 56 through clamps 116 even when all trolleys are prevented from moving by the positions of the stops. The urethane from which belt 56 is formed is sufficiently wear resistant that it provides reliable operation even after many hours of continuous use. And, as the relative positions of clamp upper member 118 and lower member 122 are adjustable, the clamps can be repositioned in the event that the diameter of belt 56 decreases slightly after a long period of use to maintain the proper pressure on the belt.
[0047] The operation of the subject system will now be described with particular reference to FIGS. 8 a - 8 h which shows the system set up for use with a patty stacker that forms four stacks of patties simultaneously which patties must be packed in boxes that are three patties wide. Thus the buffer will receive stacks of patties four at a time from a first direction, shown by arrows 138 in FIG. 8A, on a first side of the buffer and present them for removal three stacks at a time on a second side of the buffer where they are removed in a the direction of arrows 140 in FIG. 8C.
[0048] [0048]FIG. 8A shows four trays 70 a , 70 b , 70 c and 70 d on a first side of buffer 10 which trays have just received four stacks 142 of hamburger patties from a transfer mechanism (not shown). Controller 136 causes stop 128 to move between blocking and releasing positions in order to release carriers in groups of four at predetermined intervals. After four stacks of patties are received in trays 70 a - 70 d , stop 128 shifts to its release position and allows these carriers to pass. The fifth carrier, 70 e , which is empty, and the carriers behind it, are stopped by stop 128 for a predetermined period of time, a period long enough for theses carriers to receive four more stacks of patties from the stacking machine.
[0049] As shown in FIG. 8B, additional carriers 70 f and 70 g impact against stopped carrier 70 e and are held in this position as belt 56 slips through clamps 116 on each trolley. Carriers 70 e - g will remain in this position for a predetermined amount of time. Meanwhile, carriers 70 a - d have been carried around buffer 10 by belt 56 toward a second stop 134 that blocks the path of the trays, and tray 70 a impacts against the second stop. Trays 70 b - d impact against stopped tray 70 a and are also brought to a stop with drive belt 56 sliding freely through clamps 116 on each of the stopped trays.
[0050] As shown in FIG. 8C, a second transfer device, not shown, removes three stacks of patties from carriers 70 a , 70 b and 70 c in the direction of arrows 140 , and the first transfer device places four additional stacks of patties on carriers 70 e , 70 f , 70 g and 70 h on the first side of the buffer. After a predetermined time, carriers 70 a - c will be empty, and therefore the controller cause these three trays to be released, while the next tray (the last full tray) is stopped. Full carriers 70 e , 70 f , 70 g and 70 h are released by first stop 132 in FIG. 8C and moved around the buffer until they impact full carrier 70 d held up at second stop 134 resulting in the positioning of trays shown in FIG. 8D.
[0051] [0051]FIG. 8E shows that three stacks of patties have been removed from carriers 70 d , 70 e and 70 f and that additional stacks of patties have been placed on carriers 70 i , 70 j , 70 k and 70 a . Four full carriers are released by stop 128 and three empty carriers are released by stop 132 as described above resulting in the arrangement of carriers shown in FIG. 8 f . As shown in FIG. 8G, three additional stacks of patties are removed from trays 70 g , 70 h and 70 i and these now-empty carriers are also released. Full carriers 70 j , 70 k and 70 a remain stopped at stop 132 . Three additional stacks of patties will be removed from carriers 70 a , 70 k and 70 j as shown in FIG. 8H while an additional four stacks are added to trays 70 c , 70 d , 70 e and 70 f at the first side of the buffer, and from there the process continues repeatedly as described above.
[0052] The above invention has been described above in terms of a preferred embodiment. However, obvious changes and additions to the invention will become apparent to those skilled in the relevant arts upon a reading of the foregoing disclosure. For example, while the trolleys are described as being connected to a urethane belt in a manner that allows the belt to slide through the trolleys when the motion of a trolley is blocked, a plurality of separately controllable clamps could be used on each carrier to independently control whether a given carrier is connected to a drive belt. Additional sensors could also be added to provide additional information on the position and status of carriers as they travel around the buffer. And, while the buffer has been described in terms of reducing a flow of four incoming stacks of patties to three outgoing stacks of patties, the number of incoming patties could be changed, the number of outgoing patty stacks could be greater than the number of incoming stacks or the incoming and outgoing stacks could be equal in number without departing from the scope of this invention. It is intended that all such obvious changes and additions be included within the scope of this invention to the extent that they are defined by the several claims appended hereto.
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A buffer device for buffering a flow of stacks of discrete objects between a stacking machine and a packaging machine is disclosed which buffer includes a plurality of individual trays mounted on carriers which carriers are mounted on a frame and driven about the periphery of the frame by a drive. A first number of stacks of objects is placed on a first number of carriers on a first side of the frame and a second number of stacks are removed from a second number of carriers on a second side of the frame where the first number can be greater than, less than or equal to the first number. The carriers clamp onto a continuously moving drive belt in a manner that allow the drive belt to slip through the carrier clamps when motion of the carriers is obstructed. A method of using the buffer device is also disclosed.
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US REFERENCES
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FOREIGN REFERENCES
[0000]
WO/2002/087683 (2002 Jul. 11) Ehud Cohen, Actuation and control of limbs through motor nerve stimulation
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BACKGROUND OF THE INVENTION
[0009] The field to which this invention pertains is that of biotechnological implants. More specifically, it relates to the field of neuroprosthetics. Although a relatively new field, many types of devices have been made to detect signals coming from the nervous system ( 1 ). The (eventual) goal of many of these technologies is to repair damaged nerves, or to provide control for prosthetic/electronic devices. Currently, much work is being done using implantable micro-electrode arrays made of various metals, to gather information from or supply information to the nervous system ( 2 ). These devices have been used to allow paralyzed individuals to control computer cursors using only their minds, allow monkeys to control robotic actuator, and well as provide very limited sight data to the blind.
[0010] These techniques and devices have however fallen far short of their intended goals for various reasons. The first is that these technologies are in their infancy and their development in many respects is a matter of time. The second reason is that many researchers approach nervous system data as they approach any other data, by collecting and analyzing massive quantities of it before taking any action (empirically). This second reason leads directly to the third; the inclusion of massive computing devices and software systems to record, analyze, and manipulate signals coming from the body into a form that is readable by machines or to perform those functions on incoming data so that it is readable by the nervous system. The fourth issue is signal fidelity and resolution. Current microelectrodes are so large (although still microns in diameter) that each one receives signals from tens of axons if not more, leading to very low signal fidelity. Microelectrode arrays currently use anywhere from 1-100 electrodes, which is very low resolution compared to that of a human body's nervous system. The fifth issue is that even if these devices were implemented successfully in their current forms, there would be little to no safeguards in place to prevent an outside party from tampering with a person's nervous system, due to the affinity toward using computer control systems to regulate these devices.
BRIEF SUMMARY OF THE INVENTION
[0011] The invention described herein is a Nanotube Micro-array Relay System for Providing Nerve Stimulation output and Sensation input between Proximal and Distal ends of a damaged Spinal Cord. The goal of this device is to provide a relay system between ends of a severed spinal cord.
[0012] This device is comprised of two opposing microelectrode arrays, each identical although facing in opposite directions, each fabricated micro circuit board containing switches, diodes, capacitors and contact points to allow signals to be passed from one micro-array to another. In order to be a viable spinal cord implant, a channel must be made in the center of the device to allow for the flow of cerebro-spinal fluid. The circuitry must be contained within a biocompatible material to allow for implantation. This sheath should be fabricated longitudinal channels to allow for the flow of cerebrospinal fluid around the spinal cord. At the crests of these channels should be synthetic material that allows the device to be sutured into place.
[0013] This device will be able to accept various power sources, that would be constructed modularly and fitted at the time of implantation, to allow for a wide range of power generation alternatives. These devices include internal batteries with induction chargers, internal batteries with internal kinetic chargers, induction coils with external battery packs and power transfer systems, or any other system that could provide an equitable power supply to this device.
[0014] This device detects the signals coming from either end of a damaged spinal cord, amplifies them, and then stimulates the axons on the opposing side from which they were received.
[0015] This device addresses the problems put forth in the previous section thusly: This device has been developed like a work of art which implements the bleeding edge technologies of the field, which have the potential to far out perform current technologies; hence it is unencumbered by the youth of the field since art is immortal. This device has no data recording or analysis functions, nor does it provide any output to a computer system. The device is self contained in respect to its data processing and has no programming beyond that defined by its hardware components. By using carbon nanotubes as electrodes this device would have signal fidelity far beyond that of current microelectrode arrays ( 3 ). Because of the small size of these electrodes, many can be placed on a single array to allow for relatively high resolution. Since this device has no computer interfaces or data manipulation capabilities it is relatively safe from outside tampering with its information relay functions.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING
[0016] Cross-sectional Side view ( FIG. 1 ). Top down view showing anterior (bottom of page)-posterior (top of page) orientation and plane of FIG. 1 ( FIG. 2 ). Dorsal view (without modular power supply) ( FIG. 3 ).
DETAILED DESCRIPTION OF THE INVENTION
[0017] The device described herein is a Nanotube Micro electrode array Relay System for Providing Nerve Stimulation output and Sensation input between Proximal and Distal ends of a severed Spinal Cord. The main components of this device are: Proximal and distal microelectrode arrays ( 1 ) and their subsequent microcircuit boards ( 2 ), the inter array junction ( 3 ), modular power supply inputs ( 4 ), a biocompatible sheath ( 5 ), a biocompatible armature ( 12 ) with suturable sections ( 6 , 7 and 8 ) and grooves for cerebrospinal fluid flow ( 9 ), a tube to provide fluid flow through the spinal cord's central canal ( 10 ), and the modular power supply ( 11 ).
[0018] The nanotube microelectrode arrays of this device should be made using a combination of standard micro lithography techniques and chemical vapor deposition.
[0019] Assuming a minimum microelectrode diameter of 2 micrometers, a maximum electrode density of 5000 electrodes per centimeter could be attained. For the purposes of this device a minimum of 500 electrodes per square centimeter is required. These electrodes should be fabricated directly onto the microcircuit boards ( 1 ) that comprise the relay and amplification system. The relay and amplification system ( 2 ) functions thusly: When a voltage is generated between a pair of electrodes by a neuronal action potential, a micro switch is activated that closes a circuit which causes a micro capacitor to discharge a voltage of roughly 100 mv (at the electrodes), which passes through the inter array junction, across a pair of electrodes on the opposing surface and then back to the capacitor. Each nanotube electrode has a partner electrode on the same array, across which voltages are detected or discharged, and a mirrored pair on the opposing array to which any signal received is transmitted. Signal transmission in this device is bi-directional however micro diodes should be used to allow for unidirectional signal transmission at any one time. These components should be made using standard micro lithography, chemical vapor deposition and laser etching techniques. The microelectrode array ( 1 ) should be assembled on the same silicon dioxide microchip as the capacitor and switching components, however they should be on opposite surfaces of the microchip.
[0020] Contacts between the two electrode arrays and subsequent circuit systems should be achieved through the use of an inter array junction ( 3 ), into which connections from each array/circuit board pass. There must be a connection for each microelectrode to connect to its mirrored electrode. The junction may have a wider area than the microelectrode array to allow for physical support that may be needed for electrical contacts between opposing arrays. The function of the junction is to allow signals to be transferred between mirrored pairs of electrodes on either array. This junction should be manufactures with vertically aligned nano wires which securely contact nano wires coming from each microarray/auxiliary circuit complex.
[0021] Each array (proximal and distal) and its auxiliary components should be identical. These arrays, when placed with their microelectrodes facing away from each other, should be joined together at the inter array junction.
[0022] This dual microarray system should be shaped to the cross-sectional dimensions of the spinal cord in the region of the spinal cord at which it would be placed. The preferred embodiment of this device would be such that arrays with different cross-sectional shapes would be made for each region of the spinal cord. These sets of devices with varying cross-sectional shapes would be made in different sizes to allow them to be used on a wide range of individuals with spinal cord damage at varying regions of the cord.
[0023] Passing through the center of the arrays, circuits and inter array junction, should be a biocompatible polyethylene tube ( 10 ), placed so that it mates on either side of the device with the central canal of the spine. This would allow for an unimpeded flow of cerebrospinal fluid through the device.
[0024] Power to this system should be provided through two leads ( 4 ) that pass from each circuit board, through the biocompatible housing of the device (to be discussed below), and into ports that allow for the connection of the modular power supply apparatus. Four leads in total are needed, two for each array.
[0025] The opposing arrays, microcircuits, and the inter array junction should all be contained within a biocompatible sheath. Said sheath should be made of biocompatible polyethylene (or a comparable material) that is machined or molded using sterile, surgical grade, fabrication techniques. Said sheath should have chamfers that fit around the perimeter of the micro electrode arrays. Said sheath should be flexible enough to be fitted as a single piece around both arrays and auxiliary components and glued into place (using a surgical grade epoxy or “super-glue” to provide a non degradable seal impenetrable to bodily fluids. Said sheath must have sealed ports to allow for power supply leads to pass through it.
[0026] Over the sheath a biocompatible armature ( 12 ) should be fitted. It should be attached to the sheath using an appropriate adhesive or a mechanical connection. The functions of this armature are multifold. It must be biocompatible (a thicker polyethylene or comparable material is appropriate). It must have channels ( 9 ) through which cerebrospinal fluid can pass unimpeded. These channels may be simple longitudinally oriented grooves in the body of the armature to allow for fluid flow. It must have longitudinally oriented regions that allow for suturing ( 7 ) and/or tissue in-growth (fabrics such as those used in arterial grafts are appropriate). These regions may be fixed to the body of the armature using a chamfered channel travelling the length of the longitudinal suturing regions ( 7 ), along with an appropriate adhesive. These regions are meant to be sutured through the Dura mater of the spinal cord.
[0027] The armature must have a suturable region travelling the circumference of the openings into which the proximal and distal ends of the spinal cord pass ( 6 ). This suture ring is intended to affix the proximal and distal ends of a severed spinal cord to the device. This suture ring should not impede the flow of cerebrospinal fluid and should not extend to the distance (measured from the central canal duct ( 10 ) outward) of the longitudinally oriented suturing regions. These regions are intended to be sutured directly to the spinal cord or to the Pia matter. These regions may be affixed to the armature by means of a chamfered channel travelling the circumference of the openings which accommodate the proximal and distal ends of a severed spinal cord, along with an appropriate adhesive. These channels should be oriented parallel to the spinal cord.
[0028] The armature must have a suturable region travelling the circumference of the modular power supply port ( 8 ). This region is oriented perpendicularly to suturable region ( 6 ), and should travel the circumference of the region which allows for attachment of the modular power supply. This suturable region ( 8 ) is intended to affix the Dura matter of the spinal cord around the circumference of the modular power supply attachment region. By doing so, the modular power supply ( 11 ), rests outside of the tissues sheathing the spinal cord, thereby allowing modular power supplies to be interchanged (post-operatively) without having to make an incision into the sheaths of the spinal cord.
[0029] The armature must have ports to connect the power leads ( 4 ) leaving the inner sheath to the modular power supply ( 11 ). The armature, lastly, must have a means of securely attaching the modular power supply ( 11 ).
[0030] The modular power supply ( 11 ) of this for this apparatus is any device that can fit in the attachment area of the armature and provide an appropriate power supply to the power leads ( 4 ) of the apparatus. The coupling between the device and the modular power supply should take place outside the Dura matter of the spinal cord, into which the main body of the biocompatible armature is sutured. This should be affected by having the coupling area protrude dorsally from the main body of the device. This protrusion should be continuous with the biocompatible armature. This protrusion should have internally facing chamfers and be surrounded by a cuff of material capable of being sutured ( 8 ). The junction between the main device and the modular power supply can affected by any means capable of attaching the power supply adequately and that does not impede biocompatibility or implantability. The method of attaching the modular power supply pictured in FIG. 1 is a pressure fitting, which would allow the modular power supply to be pushed into position and firmly held by the internal chamfer of the modular power supply attachment region. The power supply of this device is should be modular to allow for upgrades to the power supply system over the life of the implant without having to remove the main body of the device.
[0031] The preferred method of powering this device would be a kinetic charger/rechargeable battery apparatus to generate power by means of body movement. Other methods that can be utilized are an internal induction coil/rechargeable battery system that would be charged periodically with an external induction coil/rechargeable battery system linked to a generator (solar/kinetic), or to a stationary power source. These methods are preferable power solutions as they would provide unimpeded and (largely) self generated electrical power. Other modular devices are acceptable so long as they provide an appropriate power supply, attach to the armature, and allow for uninterrupted power delivery.
[0032] For this device to be implemented surgically, the region to be repaired must be prepped for the implant. Preparation of the area requires that the damaged ends of the spinal cord must be cut so that they provide a flat plain perpendicular to the length of the cord. The vertebrae in the region to be repaired must also be immobilized (temporarily or permanently, depending on consultation with a surgeon and the patients activity level) using pre existing vertebral fusion/immobilization techniques. It should be implanted using appropriate microsurgery techniques.
[0033] Implementation of this device would be most favorable when coupled with physical therapy including biofeedback, exercise, and external stimulation of muscle groups. Any post operative therapies should be discussed with a physician.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0034] Not Applicable
REFERENCE TO SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING COMPACT DISC APPENDIX
[0035] Not Applicable
CITATIONS
[0000]
(1) Gasson, Mark et. al. “Invasive neural prosthesis for neural signal detection and nerve stimulation.” International Journal of Adaptive Control and Signal Processing. 19.5 (2004): 365-375.
(2) Ibid.
(3) WO/2002/087683 (2002 Jul. 11) Ehud Cohen, Actuation and control of limbs through motor nerve stimulation
US REFERENCES
[0000]
5092332 (1992 Mar. 3) Philip Lee, Steroid eluting cuff electrode for peripheral nerve stimulation
4541432 (1985 Sep. 17) Pedro Molina-Negro, Electric nerve stimulator device
20080071321 (2008 Mar. 20) Joseph W. Boggs II, Systems and methods of neuromodulation stimulation for the restoration of sexual function
4969468 (1990 Nov. 13) Charles L. Byers, Electrode array for use in connection with a living body and method of manufacture
7292890 (2007 Nov. 6) Todd K. Whitehurst, Vagus nerve stimulation via unidirectional propagation of action potentials
20080228240 (2008 Sep. 16) David J. Edell, Long term bi - directional axon - electronic communication system
FOREIGN REFERENCES
[0000]
WO/2002/087683 (2002 Jul. 11) Ehud Cohen, Actuation and control of limbs through motor nerve stimulation
WO/2007/109228 (2007 Sep. 27) Javed Kahn, Apparatus for microarray binding sensors having biological probe materials using carbon nanotube transistors
OTHER REFERENCES
[0000]
Anthony, Catherine Parker (1975). “Textbook of Anatomy and Physiology” 9 th edition.
C.V. Mosby Company
Gray, Henry (1930). “Anatomy of the Human Body” 22 nd edition.
Philadelphia: Lea and Febiger
Martini, Frederic H. (2009). “Human Anatomy” 6 th edition.
San Francisco: Pearson Education
Silverthorn, Dee Unglaub (2007). “Human Physiology: An integrated approach” 4 th edition.
San Francisco: Pearson Cummings
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The invention described herein is a Carbon Nano-tube Micro-electrode Array Relay System for Providing Nerve Stimulation output and Sensation input between Proximal and Distal ends of a damaged Spinal Cord. This device detects the signals coming from either end of a damaged spinal cord, amplifies them, and then stimulates the axons on the opposing side from which they were received. This device is intended to provide self-contained data relay for the goal of restoring function to a severed spinal cord. It is not intended for data output to an external source for analysis. This device is biocompatible and has a modular power system.
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[0001] REFERENCE TO RELATED APPLICATION
[0002] This is a continuation-in-part application of U.S. patent application Ser. No. 09/997,907,filed Nov. 30, 2001.
FIELD OF THE INVENTION
[0003] This invention relates to a fuel tank,assembly and more particularly to a fuel tank assembly having a low profile fuel delivery module.
BACKGROUND OF THE INVENTION
[0004] Traditionally, fuel tank assemblies have a fuel tank with an access hole covered by a flange. An elongated fuel delivery module is carried by and projects downward from the flange, stopping just short of or bearing on the fuel tank bottom. The overall length of the module is generally dictated by an electrical motor and fuel pump disposed in series along a vertical rotational axis. The vertical module length dictates the depth or minimum vertical height of the fuel tank or reservoir. Therefore, the optimum profile of the fuel tank is limited by the vertical length of the fuel delivery module. And, to optimize the already restricted profile, the tank access hole must be located on an upper horizontal surface, and most probably, the highest elevated surface of the fuel tank.
[0005] Locating the access hole on top of the tank is seldom the preferred location for maintenance purposes since the tank must be removed from the vehicle prior to accessing the internal components of the fuel tank assembly through the access hole. Because the fuel delivery module is cantilevered from the flange, the flange and the interconnection to the fuel tank itself must be robust and designed so as to pass high speed vehicle crash tests which create high torque or torsional forces upon the flange. The larger the flange, the more likely the flange seal will fail. Unfortunately, much of the available flange surface area is occupied by the fuel delivery module so that use of the flange surface area for other component mountings, or penetrations into the fuel tank, is limited.
SUMMARY OF THE INVENTION
[0006] This invention provides a low profile fuel tank assembly having a preferably elongated fuel delivery module mounted generally horizontally within the fuel tank independent of a flange which covers a sole fuel tank access hole. An integrated fuel pump and associated electric motor of the module has a rotational axis preferably disposed substantially horizontal within the fuel tank. Because the fuel delivery module is supported by the fuel tank shell or bottom, independent of the flange, the access hole can be located anywhere on the fuel tank in order to simplify fuel tank ingress and minimize repair procedures. During assembly, the module is preferably inserted into the fuel tank through the access hole, and is then secured to a bracket or strap assembly attached to the inside surface of the fuel tank, preferably via laser welding.
[0007] Preferably, the fuel delivery module is inserted into the bracket directly adjacent to a base plate of the bracket secured to the inner bottom of the tank. During assembly, the fuel delivery module is centered laterally upon the base plate of the bracket by two opposing sides projecting upward from the base plate. The module is preferably also centered longitudinally upon the base plate by two pairs of opposing stop tabs projecting upward from end edges of the base plate.
[0008] In a first embodiment of the bracket, the fuel delivery module engages the bracket by sliding horizontally along interlocking rails formed on both sides of the module and into the mounting bracket between a clasp of the bracket and a support structure of the module. Preferably, a forward tab of the bracket prevents the module from sliding too far forward. The module snap locks in place with the bracket, preventing rearward movement and disengagement, via an upward projecting locking tab of the bracket and a forward projecting snap clip of the support structure which resiliently engages the locking tab.
[0009] In a second embodiment of the bracket, the base plate is part of a resilient tray which engages at least one resilient strap at both ends of the strap. The bracket is designed to reduce shear forces placed upon the welds between the tank and the base plate during impact scenarios. To do this, the fuel delivery module is encircled by the tray and the strap. The strap is in tension when extended over and engaged directly to the fuel delivery module and a clearance exists between the module and the sides or curbs of the tray permitting some movement of the module with respect to the bracket.
[0010] Objects, features and advantages of this invention include providing a low profile fuel tank assembly thereby reducing surrounding design restraints of a vehicle fuel tank and the vehicle using it, simplifying fuel system maintenance procedures by enabling easier fuel tank ingress, reducing flange size to improve sealing, freeing up flange surface area for additional component penetrations into the fuel tank, and reducing fuel permeation while providing a relatively simple, design and a low cost rugged, durable, and reliable fuel delivery module and tank assembly.
DESCRIPTION OF THE DRAWINGS
[0011] These and other objects, features and advantages of this invention will be apparent from the following detailed description, appended claims, and accompanying drawings in which:
[0012] [0012]FIG. 1 is a perspective view of a fuel delivery module and tank assembly with part of the fuel tank broken away and in section to show internal detail;
[0013] [0013]FIG. 2 is a perspective view of a fuel delivery module, mounting bracket and a flange of the assembly of FIG. 1;
[0014] [0014]FIG. 3 is a section view of the fuel delivery module and mounting bracket taken along line 3 - 3 of FIG. 1;
[0015] [0015]FIG. 4 is a front end perspective view of the fuel delivery module and bracket;
[0016] [0016]FIG. 5 is a perspective view of the bracket;
[0017] [0017]FIG. 6 is an exploded partial cross section view of the fuel delivery module and bracket taken along line 6 - 6 of FIG. 3;
[0018] [0018]FIG. 7 is a perspective view of the fuel delivery module and bracket with part of a fuel filter broken away to show internal detail;
[0019] [0019]FIG. 8 is a section view of the fuel delivery module and bracket taken along line 8 - 8 of FIG. 2;
[0020] [0020]FIG. 9 is a section view of the fuel delivery module and bracket taken along line 9 - 9 of FIG. 3;
[0021] [0021]FIG. 9A is a perspective view of a second embodiment of a fuel delivery module, bracket and tank assembly with part of the fuel tank broken away and in section to show internal detail;
[0022] [0022]FIG. 9B is a perspective view of the second embodiment of the bracket illustrated in an open position; and
[0023] [0023]FIG. 9C is a perspective view of the second embodiment with the fuel delivery module placed within the bracket and the bracket illustrated in an open position.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0024] Referring in more detail to the drawings, FIG. 1 illustrates a fuel tank assembly 10 having a fuel tank 12 with an access hole 14 , being large enough, so that an elongated fuel delivery module 16 can be inserted into a fuel chamber 13 defined by the fuel tank 12 . A leading end 18 of the module 16 is positioned in front of a receiving end of an elongated bracket 20 welded to a bottom surface or wall 22 of an inner surface 23 of the fuel tank 12 . The bracket 20 and module 16 can be located on any other inner surface of the fuel tank 12 ; however, positioning the module on the bottom surface eliminates the need for a pump inlet tube which could contribute toward fuel vapor lock. Also, because the longitude of the module 16 is horizontal the shape of the fuel tank 12 is enabled to have a low profile, not otherwise available. The fuel tank 12 is preferably made of a blow molded plastic or high density polyethylene, HDPE, and the bracket 20 is made of an injected plastic or HDPE. Being of substantially like material, the plastic bracket 20 is welded to the inner surface 23 of the bottom wall 22 , likewise, in a substantially horizontal position. The access hole 14 is covered and sealed or closed by a flange 24 as best shown in FIG. 2.
[0025] Traditionally, the access hole 14 is positioned at the upper most part of the fuel tank 12 because the fuel delivery module is commonly mounted in a vertical direction and carried by the flange. Since the fuel delivery module 16 of the present invention is not carried by the flange 24 , the access hole 14 can be located any where on the fuel tank 12 . In fact, the access hole 14 can easily be located through any side of the fuel tank 12 . Such positioning options are desirable to facilitate fuel tank assembly, maintenance and repair. Aside from the vertical mounting and flange support of traditional assemblies, the module 16 of the present invention can be identical to the fuel pump assembly described in Bucci et al., U.S. Pat. No. 4,860,714 and incorporated herein by reference.
[0026] Referring to FIGS. 2 - 5 , in assembly, the fuel delivery module 16 is slidably received between opposing clasps 26 which project upward from a substantially planar base plate 30 of the bracket 20 and into the fuel chamber 13 defined by the fuel tank 12 . The base plate 30 is welded, embedded, or otherwise attached to the substantially horizontal bottom wall 22 of the fuel tank 12 and extends from a forward portion 34 to a rearward portion 32 . When utilizing HDPE fuel tank shells having multi-layers with an intermediate fuel permeation barrier layer, not shown, it is preferable not to breach the permeation barrier layer when securing the bracket 20 to the fuel tank 12 . Therefore, welding to the bottom surface 22 or inner layer of the multi-layered fuel tank is a preferred method of attachment. Another method, not shown, is to mold protrusions within the fuel tank during the tank manufacturing blow molding process. The bracket 20 , or the module 16 directly, can then be press fitted to the protrusions.
[0027] Referring to FIGS. 4 - 6 , when assembled, the clasps 26 prevents upward movement of the fuel delivery module 16 away from the base plate 30 , via an elongated guideway 36 of each clasp 26 which slideably engages an interlocking rail 38 of the fuel delivery module 16 . The guideways 36 and rails 38 extend longitudinally between the forward and rearward portions 34 , 32 of the bracket 20 . Preventing the module 16 from moving excessively forward and disengaging from the guideways 36 and rails 38 is a stop tab 40 projecting unitarily upward from the base plate 30 and being engageable with the leading end 18 of the fuel delivery module 16 . In assembly, rearward movement of the fuel delivery module 16 with respect to the bracket 20 , which could otherwise disengage the interlocking guideways and rails 36 , 38 in the rearward direction, is prevented by locking tabs 42 of the bracket 20 which project upward from each clasp 26 and a pair of snap clips 44 of the fuel delivery module 16 which engage the locking tabs 42 . The clasps 26 are generally somewhat flexible in order to act as bottom referencing springs which are capable of absorbing bottom impact loads placed upon the fuel tank 12 .
[0028] As best illustrated in FIGS. 3, 5 and 6 , the guideways 36 of each of the laterally opposed clasps 26 each have a channel 54 defined by a rail 48 extending longitudinally of the bracket and fixed at a right angle to a cross bar 47 attached to the upper edge of a substantially planar wall 46 which projects perpendicularly upward from the base plate 30 and extends longitudinally lengthwise of the bracket 20 . The rail 48 projects downward toward the base plate 30 from a longitudinal extending edge of the cross bar 47 and extends parallel to the wall 46 . In assembly each channel 54 receives and interlocks with one of the upward projecting rails 38 of a support structure or can 52 of the fuel delivery module 16 . The rail 38 extends longitudinally, projects upward, and along its lower edge is fixed to a traverse spacer bar 56 attached to the can 52 . Preferably the can has a side surface 50 which is spaced from and extends parallel to the rail 38 to define therewith a channel or slot 58 in which the rail 48 is disposed when the fuel delivery module 16 is engaged to the bracket 20 .
[0029] Referring to FIGS. 3 and 6, the snap clips 44 are attached each to one of both longitudinal sides 50 of the can 52 . The snap clips 44 are disposed over and are spaced vertically above the rails 38 of the can 52 so that the bar 47 of the clasp 26 on the bracket 20 can fit there-between. Each snap clip 44 has a catch or lip 64 on one end of a flexible arm 64 with its other end cantilevered and attached by a base 60 to the longitudinal side 50 of the can 52 . The base 60 serves to support and space the cantilevered arm 62 laterally outward from the longitudinal side 50 . The cantilevered arm 62 is disposed substantially parallel to the longitudinal side 50 and projects in a forward direction, as best shown in FIG. 2. The lip 64 projects laterally outward with respect to the arm 60 and the longitudinal side 50 . As the fuel delivery module 16 slides into the bracket 20 , the locking tab 42 causes the cantilevered arm 62 of the snap clip 44 to flex inward toward the longitudinal side 50 of the can 52 and the lip 64 to slide along an inner surface of the locking tab 42 . The cantilevered arm 62 snaps back or unflexes when the lip 64 slides past the locking tab 42 to overlap and engage a forward facing stop surface 66 of the locking tab 42 . Abutment of the lip 64 of the snap clip 44 with the stop surface 66 of the locking tab 42 prevents the fuel delivery module 16 from moving rearward and disengaging from the interlocking guideways 36 and rails 38 . To permit removal of the fuel delivery module 16 from the bracket 20 , a lateral inward force is applied to the arms 62 of the snap clips 44 (which extends vertically above the locking tab 42 ). When this disengaging lateral force is applied to both clips, the lips 64 separate from their respective locking tabs 42 permitting the fuel delivery module to slide rearwardly.
[0030] During assembly, alignment of the fuel delivery module 16 for insertion between the opposing clasps 26 is guided by angled or inclined guide plates 68 of the clasps 26 . Each guide plate 68 is substantially planar, angled outward and projects rearward from both the rear vertical edge of the locking tab 42 and the rear edge of the wall 46 of its associated clasp 26 . The combination of both guide plates 68 of the clasps 26 forms a type of funnel which helps to guide and align the fuel delivery module 16 between the opposing clasps 26 . The bar 47 reinforces the guide plate 68 by extending rearward to and engaging a midsection of the guide plate 68 .
[0031] As further illustrated in FIGS. 7 - 9 , the can 52 of the fuel delivery module 16 carries a fuel supply pressure control assembly 70 which is illustrated as a pressure control regulator mounted to the outlet of a fuel pump and motor 72 having a rotational axis 74 disposed substantially horizontal and preferably slanted not more than ten degrees from an imaginary horizontal plane when the fuel tank is in its normal orientation within the vehicle. However, the pressure control assembly 70 can also be a pressure transducer motor speed control system where a fuel pressure transducer feeds back to a variable speed fuel pump. An advantage of this system is that less energy is consumed since the pump does not run at full system voltage all the time as does the pressure regulator.
[0032] Fuel flows from a reservoir carried by the can 52 via the fuel pump and motor 72 disposed within the can 52 . From pump 72 , the fuel flows through an elongated fuel filter 75 of the module 16 and to the regulator 70 , as best shown in FIG. 8. The filter 75 partially wraps about the pump and motor 72 and has a fuel inlet nozzle 82 mounted to an end of the filter 75 which is opposite or away from the regulator 70 . A fuel level sensor assembly 77 , which includes a pivoting float arm sensor 78 and/or a fuel piezo level sensor 76 , are integral to the module 16 . The pivoting float arm sensor 78 functions off a fixed ohm resistor card with variable resistance controllable by a float engaged to the distal end of a pivoting arm.
[0033] Various attachments on the module 16 lead to and extend through the flange 24 . These attachments include a wiring harness (not shown) and a flexible tube 80 for supplying fuel to the engine and which communicates with the regulator 70 via a nozzle 81 engaged unitarily to the can 52 . Because flange 24 of the present invention does not carry or support the fuel delivery module 16 , other components are easily supported by the flange 24 . These components include, but are not limited to, an on-board diagnostic-two pressure transducer, OBD2, for detecting fuel tank leakage via pressure differential, and a fill limit vent valve, FLVV.
[0034] Referring to FIGS. 9 A- 9 C, a second embodiment of a fuel delivery assembly 10 ′ is useful in absorbing shock, or G-forces, therefore relieving stress placed upon the tank to bracket interface and the fuel module to bracket interface. The strapped bracket 20 ′ allows the fuel delivery module 16 ′ to move slightly in any direction which acts to decelerate the module over a longer time period than the stiffer first embodiment during high impact scenarios.
[0035] Laser welds 90 , which require no special tank features or contours, secure a substantially planar base plate 30 ′ of a base unit or tray 89 of the bracket 20 ′ to the inner surface 23 ′ of the fuel tank 12 ′. There are four welds 90 illustrated in FIG. 9B, however, there may be more or less depending upon the weight of the fuel delivery module 16 ′ and the configuration of the fuel tank assembly 10 ′. The tray 89 is preferably made of like material to the inner surface 23 ′ of the fuel tank 12 ′. As one example, if the fuel tank is HDPE, preferably, the tray 89 is also made of HDPE to enhance the strength of the weld. However, because HDPE has a tendency to swell when soaked with hydrocarbon fuel, the tray 89 should also be reinforced with integral glass fibers to reduce swelling. The laser weld 90 is preferred over plate welding because the tray 89 is designed to flex and is too thin to handle the high heat produced during the plate welding process. Laser welding is also advantageous because the laser weld equipment permits off-setting the bracket 20 ′ away from the tank access hole 14 ′. This off-set can generally be as great as six to twelve inches for a typical automotive fuel tank application. Fiber optics are used to locate the weld between the bracket 20 ′ and the tank 12 ′. When utilizing a laser light wavelength of approximately 800 nm, the welding process takes about three to five seconds.
[0036] Initially locating the fuel delivery module 16 ′ to the bracket 20 ′ are first and second side guide plates or side curbs 92 , 94 of the tray 89 which substantially oppose one-another, performing similarly to the guide plates 68 of the first embodiment. The side curbs 92 , 94 project substantially upward from respective longitudinal edges of the base plate 30 ′, and extend longitudinally of the base plate 30 ′ between forward and rearward stop tabs 96 , 98 of the tray 89 . The forward stop tabs 96 function similarly to the stop tab 40 of the first embodiment, limiting forward movement of the fuel delivery module 16 ′ within the bracket 20 ′. The forward stop tabs 96 extend inward toward one-another from respective ends of the curbs 92 , 94 and along a minor portion of a lateral or forward edge 100 of the base plate 30 ′. The additional rearward stop tabs 98 of the second embodiment limit rearward movement of the fuel delivery module 16 ′ within the bracket 20 ′, and extend inward toward one-another along a minor portion of a rearward edge 102 of the base plate 30 ′ from respective ends of curbs 92 , 94 .
[0037] After the base plate 30 ′ of the tray 89 is laser welded to the tank 12 ′, an elongated support structure or can 52 ′ of the elongated fuel delivery module 16 ′ is placed into the tray 89 from a substantially vertical direction. The forward and rearward stop tabs 96 , 98 align the can 52 ′ longitudinally to the tray 89 , and the first and second curbs 92 , 94 align the can 52 ′ laterally to the tray 89 .
[0038] A resilient forward and rearward pair of straps 104 , 106 , secure the module 16 ′ resiliently and directly against the welded base plate 30 ′. Each pair of straps 104 , 106 has a long mid strap 108 and a shorter end strap 110 which extend snugly and resiliently over a contoured fuel filter 75 ′ of the module 16 ′ engaged to the can 52 ′. Preferably, opposite ends 112 , 114 of the straps 108 , 110 of both pairs extend between and are engaged unitarily to a first and a second flap 116 , 118 . The first flap 116 is illustrated as being hinged unitarily to a raised portion 120 of the first curb 92 along an axis disposed longitudinally of the base plate 30 ′. The second flap 118 snap locks to a raised portion 122 of the second curb 94 via a snap locking feature, or two respective apertures 126 communicating through the second flap 118 which snugly receive two protuberances 124 projecting outward from the second raised portion 122 . A thumb catch 128 projects outward from the second flap 118 between the apertures 126 to assist the user in snap locking the second flap 118 and straps 108 , 110 from an open position 130 to a closed or locked position 132 .
[0039] Because the bracket 20 ′ is illustrated as one unitary part, the straps 108 , 110 are made of the same material as the base plate 30 ′ which is preferably HDPE. The straps must be thin enough to enable stretching across the fuel filter 75 ′ thus providing a degree of give or resilience. The thickness of the strap necessary to achieve this resilience is thus dependent upon the material used.
[0040] Alternatively, the straps 108 , 110 and the flaps 116 , 118 can be unitary with each other, yet separate as a single molded unit from the base plate 30 ′. With this configuration, the first flap 116 has a snap locking feature instead of the resilient hinge. As a separate entity, the straps and flaps can be made of a material with excellent elastic properties yet different than the material of the base plate 30 ′ which must be similar to the tank 12 ′ material for welding purposes. One such material for the straps and flaps is nylon.
[0041] As presently illustrated, the fuel filter 75 ′ of the fuel delivery module 16 ′ is supported by and protrudes upward from the can 52 ′. A substantially outward facing contoured surface 134 of the filter 75 ′ disposed above the can 52 ′ is in direct contact with the resilient straps 108 , 110 . The contoured surface 134 has a forward shelf or shoulder 136 which substantially lies within an imaginary plane disposed perpendicular to the base plate 30 ′. The forward shelf 136 is contiguously defined between and disposed substantially perpendicular to a leading proximal portion 138 of the contoured surface 134 and a distal mid portion 140 . The short strap 110 of the forward pair 104 is resiliently engaged directly to the leading proximal portion 138 of the contoured surface 134 . The longer mid strap 108 of the forward pair is directly engaged resiliently to the distal mid portion 140 disposed generally further away from the base plate 30 ′ than the forward proximal portion 138 . During high impact scenarios, the forward shelf 136 will contact the short strap 110 of the forward pair 104 thereby limiting the forward movement of the fuel delivery module 16 ′ within the bracket 20 ′.
[0042] Likewise, the contoured surface 134 of the fuel filter 75 ′ has a rearward shelf 142 which lies within an imaginary plane disposed substantially parallel to the forward shelf 136 . The rearward shelf 142 is defined contiguously between and disposed substantially perpendicular to a trailing proximal portion 144 of the contoured surface 134 and the distal mid portion 140 . The short strap 110 of the rearward pair 106 is resiliently engaged directly to the trailing proximal portion 144 of the contoured surface 134 . The longer mid strap 108 of the rearward pair 106 and the longer mid strap 108 is directly engaged resiliently to the distal mid portion 140 . During high impact scenarios, the rearward shelf 142 will contact the stretchable short strap 110 of the rearward pair 106 thereby limiting the rearward movement of the fuel delivery module 16 ′ within the bracket 20 ′. Depending upon dynamics of the environment and the shape and weight distribution of the fuel delivery module 20 ′ other strap configurations can also suffice. For instance, one short strap may secure the module by engaging the filter's contoured surface from within a channel defined by the surface 134 .
[0043] Referring to FIG. 9C, movement of the fuel delivery module 16 ′ with respect to the base plate 30 ′ and the laser welds 90 is limited to about two millimeters for a typical automotive fuel tank application. With the fuel delivery module 16 ′ centered longitudinally to the base plate 30 ′ by the tight relationship between the short straps 110 and the forward and rearward shelves 136 , 142 , a clearance 146 of approximately two millimeters exists between can 52 ′ and the forward tabs 96 , and the can 52 ′ and the rearward tabs 98 . To assist in similar, but lateral movement, a clearance 148 of approximately two millimeters exists between the can 52 ′ and the first curb 92 , and the can 52 ′ and the second curb 94 of the base plate 30 ′ when in an un-flexed state. Of course with the second flap 118 snap locked to the raised portion 122 , the clearance 148 is effectively eliminated at the raised portion 120 , 122 junctures.
[0044] Also to assist in flexing of the tray 89 , two cut-outs 150 communicate through and extend laterally across the base plate 30 ′ and partially upward communicating through each side curb 92 , 94 , but stopping short of the raised portions 120 , 122 .
[0045] While the forms of the invention herein disclose constitute a presently preferred embodiment, many others are possible. For instance, the opposing clasps 26 can be replaced with a strap which wraps around the module 16 and engages the base plate of the alternative bracket at either end. It is not intended herein to mention all the equivalent forms or ramifications of the invention, it is understood that the terms used herein are merely descriptive rather than limiting and that various changes may be made without departing from the spirit or scope of the invention.
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This invention provides a low profile fuel tank assembly having an elongated fuel delivery module mounted horizontally within the fuel tank and independent from a flange which covers a sole fuel tank access hole. An integrated fuel pump and associated motor of the module dictates the length of the module. The motor and pump has a rotational axis preferably disposed substantially horizontal within the fuel tank. Because the fuel delivery module is supported by the fuel tank shell or bottom, independent of the flange, the access hole can be located anywhere on the fuel tank in order to simplify fuel tank ingress and minimize repair procedures. During assembly, the module is inserted into the fuel tank through the access hole, and is then placed and snap-locked preferably into a bracket structure permanently engaged to an inside surface of the fuel tank.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a combination of a golf club head and a weight member.
[0003] 2. Description of Related Art
[0004] FIG. 1 of the drawings is a sectional view of a conventional golf club head, and FIG. 2 is a sectional view of another conventional golf club head. The golf club head 10 is made of a material having a low specific gravity (or relative density) such as a titanium alloy, stainless steel, Fe—Mn—Al alloy, soft iron alloy, or other iron alloy. A weight member 20 is embedded in the golf club head 10 and made of a material having a high specific gravity, such as a W—Fe—Ni alloy or other tungsten alloy. The golf club head 10 includes a recession 11 ( FIG. 1 ) or notch 101 ( FIG. 2 ) into which the weight member 20 is securely fixed by an appropriate means to form a golf club head product with a lower center of gravity while increasing the overall volume of the golf club head, increasing the thickness of the golf club head, and improving the striking effect without changing the overall weight.
[0005] Nevertheless, when bonding the golf club head 10 and the weight member 20 made of different materials together by welding, heat cracks and poor welding bead solidifying patterns are apt to be generated. Therefore, brazing is usually used in the golf club head industry to bond the golf club head body 10 and the weight member 20 together. Nevertheless, the cost for brazing is high, as brazing includes use of a welding material containing expensive ingredients, such as silver, copper, titanium, nickel, etc. Further, metallographic arrangement and crystalline microstructure are adversely affected, as the golf club head 10 and the brazing material must be heated simultaneously. The overall structural strength and toughness of the golf club head are thus adversely affected. Further, it is difficult to control the amount of the welding material, the engaging relationship between the wall delimiting the recession 11 and the weight member 20 , and the force for inserting the weight member 20 . Further, a paste that is generally included in the brazing material comprises organic materials that easily volatilize when heated, resulting in outflow of the brazing material, unreliable filling of a gap between the weight member 20 and the wall delimiting the recession 11 , generation of voids, and waste of the brazing material. The bonding strength for the weight member 20 by welding is adversely affected, and the operational difficulty of the brazing process is increased.
[0006] In addition to welding and brazing, the weight member 20 can be engaged with the golf club head 10 by pressing, insertion, or screwing. For example, U.S. Pat. Nos. 6,592,468 and 6,616,547 both disclose use of a bronze plate on which a plurality of weight members are formed. Although this arrangement is simpler than the welding process and the brazing process, surface crack, twist, and deformation are apt to occur to the golf club head, adversely affecting the appearance of the golf club head. Thus, this arrangement is not suitable for a golf club head having a small thickness, such as a golf club head of an XL-size wooden club.
OBJECTS OF THE INVENTION
[0007] An object of the present invention is to provide a combination of a golf club head and a weight member, wherein a filling material is used for fixing the weight member in the golf club head, providing a rapid and simplified process for mounting the weighting member into the golf club head.
[0008] Another object of the present invention is to provide a combination of a golf club head and a weight member, wherein a filling material is used for fixing the weight member in the golf club head, providing improved vibration-absorbing effect, improved striking stability, and improved gripping comfort.
[0009] A further object of the present invention is to provide a combination of a golf club head and a weight member, wherein a filling material is used for reliably fixing the weight member in the golf club head.
SUMMARY OF THE INVENTION
[0010] In accordance with an aspect of the invention, a golf club head includes a recession in a sole thereof, and a weight is securely mounted in the recession to adjust a center of gravity of the golf club head. A filling material is provided to seal the recession and to bury and fix the weight member. The filling material simplifies the process for fixing the weight member in the golf club head and receives vibrations generated as a result of striking a golf ball.
[0011] Other objects, advantages and novel features of this invention will become more apparent from the following detailed description when taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 is a sectional view of a conventional golf club head;
[0013] FIG. 2 is a sectional view of another golf club head;
[0014] FIG. 3 is a sectional view of a first embodiment of a golf club head in accordance with the present invention;
[0015] FIG. 4 is a sectional view of a second embodiment of the golf club head in accordance with the present invention;
[0016] FIG. 5 is a sectional view of a third embodiment of the golf club head in accordance with the present invention;
[0017] FIG. 6 is a sectional view of a fourth embodiment of the golf club head in accordance with the present invention;
[0018] FIG. 7 is a sectional view of a fifth embodiment of the golf club head in accordance with the present invention; and
[0019] FIG. 8 is sectional view of a sixth embodiment of the golf club head in accordance with the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0020] Preferred embodiments of the present invention are now to be described hereinafter in detail, in which the same reference numerals are used in the preferred embodiments for the same parts as those in the prior art to avoid redundant description.
[0021] Referring to FIG. 3 , a first embodiment of a golf club head 10 in accordance with the present invention is a club head of an iron club and made of a metal having a low specific gravity, such as a titanium alloy, stainless steel, Fe—Mn—Al alloy, soft iron alloy, or other iron alloy. The golf club head 10 includes a recession 11 in a sole (not labeled) thereof. A weight member 20 is inserted into the recession 11 . The recession has an opening (not labeled) that faces upward and that is sealed by the filling material 30 .
[0022] The weight member 20 is made of a material having a high specific gravity, such as a W—Fe—Ni alloy. The weight member 20 has a sectional area substantially the same as that of the recession 101 of the golf club head 10 . Thus, when the weight member 20 is mounted in the recession 11 , a perimeter of the weight member 20 is in contact with a perimeter wall delimiting the recession 11 , and a bottom face of the weight member 20 is in intimate contact with a bottom wall delimiting the recession 11 .
[0023] The filling material 30 fills the opening of the recession 11 by means of heat pressing or injection molding, thereby burying and fixing the weight member 20 in the recession 11 . Thus, the weight member 20 is reliably fixed in the recession 11 . This burying process can be performed at room temperature. The welding process, heating process, or high pressure applying process required in the prior art process for mounting a weight member into a recession of a golf club head is avoided; namely, the process for assembling the weight member 20 is expedited and simplified.
[0024] The filling material 30 is preferably made of a light material. Particularly suitable material includes a light material having a specific gravity smaller than 4.0. For example, the light material may be selected from a group consisting of resins (e.g., epoxy resin), high molecular polymer materials, rubber, thermoplastic elastomers, polyurethane elastomeric filling materials, carbon fibers, light alloys (e.g., titanium alloys, aluminum alloys, etc.), and adhesive composite powders thereof. The filling material 30 also provides a vibration-absorbing function. Thus, the vibrations resulting from striking a golf ball are absorbed by the filling material 30 , improving the vibration-absorbing effect, improving the striking stability, and improving the gripping comfort. The filling material 30 fills the opening of the recession 11 by means of heat pressing or injection molding and provides improved bonding strength and improved burying effect. Further, the center of gravity of the golf club head 10 can be advantageously shifted downward by means of selecting a filling material 30 having an appropriate specific gravity, allowing flexible adjustment in the center of gravity of the golf club head 10 .
[0025] Further, as illustrated in FIG. 3 , a striking plate 12 is engaged to a front side of the body (not labeled) of the golf club head 10 , and a hosel 13 is formed on a side of the body of the golf club head 10 . A shaft (not shown) is mounted to the hosel 13 . The striking plate 12 can be fixed to the body of the golf club head 10 by insertion, pressing, brazing, welding, or screwing. Alternatively, the striking plate 12 can be integrally formed with the body of the golf club head 10 . The body of the golf club head 10 can be integrally made by precision casting, casting, mechanical processing, pressure-casting, forging, injection molding, etc. Alternatively, the body of the golf club head 10 can be made by means of section-by-section engagement.
[0026] FIG. 4 shows a second embodiment of the invention, wherein the opening of the recession 11 faces rearward. Further, the shape of the opening of the recession 11 may vary to match the appearance of the golf club and to match the shape of the weight member 20 . For example, the opening of the recession 11 may be circular, oval, polygonal, or star-like. Further, the type and color of the filling material 30 can be selected. Alternatively, filling materials 30 of different types and colors can be used at the same time. Thus, in addition to burying the weight member 20 and absorbing vibrations generated as a result of striking a golf ball, the filling material 30 provides an aesthetic appearance on the back of the golf club head 10 .
[0027] FIG. 5 shows a third embodiment of the invention, wherein the opening of the recession 11 faces downwardly. The filling material 30 is, e.g., a polyurethane elastomeric filling material or rubber to provide a buffering effect and anti-sliding effect while burying the weight member 20 and absorbing vibrations as a result of striking a golf ball.
[0028] FIG. 6 illustrates a fourth embodiment of the invention, wherein a perimeter wall delimiting the recession 11 of the golf club head 10 includes a plurality of grooves 111 adjacent to the opening of the recession 11 . The grooves 111 can be arranged to in annular, star-spangled, or irregular manner. The grooves 111 allow the filling material 30 to be securely engaged in the opening of the recession 11 in a “snapping” manner, preventing the filling material 30 from disengaging from the recession 11 . The bonding reliability of the weight member 20 is thus improved. Further, to avoid adverse affect to the distribution of the momentum imparted by the striking plate 12 , the grooves 111 are preferably formed on a rear side of the striking plate 12 .
[0029] FIG. 7 shows a fifth embodiment of the invention, wherein the golf club head 10 is a club head of a wooden club that includes a compartment 100 , a recession 11 , a striking plate 12 , and a hosel 13 . The recession 11 is an extension extending from the sole toward the compartment 100 . A weight member 20 is mounted in the recession 11 , and a filling material 30 is then filled into the recession 11 to bury and fix the weight member 20 , thereby expediting and simplifying the process for mounting the weight member 20 . The filling material 30 also absorbs vibrations generated as a result of striking a golf ball and provides an aesthetic appearance on the back of the golf club head 10 , as the case of the second embodiment of FIG. 4 .
[0030] FIG. 8 shows a sixth embodiment of the invention modified from the fifth embodiment, wherein the a perimeter wall delimiting the recession 11 of the golf club head 10 includes a plurality of grooves 111 adjacent to the opening of the recession 11 . The grooves 111 can be arranged to in annular, star-spangled, or irregular manner. The grooves 111 allow the filling material 30 to be securely engaged in the opening of the recession 11 in a “snapping” manner, preventing the filling material 30 from disengaging from the recession 11 . The bonding reliability of the weight member 20 is thus improved.
[0031] While the principles of this invention have been disclosed in connection with specific embodiments, it should be understood by those skilled in the art that these descriptions are not intended to limit the scope of the invention, and that any modification and variation without departing the spirit of the invention is intended to be covered by the scope of this invention defined only by the appended claims.
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A golf club head includes a recession in a sole thereof. A weight member is mounted in a recession of the golf club head for adjusting the center of gravity of the golf club head. A filling material seals the recession and buries/fixes the weight member in the recession. The filling material simplifies the process for mounting the weight member and absorbs vibrations generated as a result of striking a golf ball.
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FIELD OF THE INVENTION
[0001] This invention relates generally to a spinal implant assembly for implantation into the intervertebral space between adjacent vertebral bones to simultaneously provide stabilization and continued flexibility and proper anatomical motion, and more specifically to such a device which utilizes a wave washer as a force restoring element.
BACKGROUND OF THE INVENTION
[0002] The bones and connective tissue of an adult human spinal column consists of more than 20 discrete bones coupled sequentially to one another by a tri-joint complex which consists of an anterior disc and the two posterior facet joints, the anterior discs of adjacent bones being cushioned by cartilage spacers referred to as intervertebral discs. These more than 20 bones are anatomically categorized as being members of one of four classifications: cervical, thoracic, lumbar, or sacral. The cervical portion of the spine, which comprises the top of the spine, up to the base of the skull, includes the first 7 vertebrae. The intermediate 12 bones are the thoracic vertebrae, and connect to the lower spine comprising the 5 lumbar vertebrae. The base of the spine is the sacral bones (including the coccyx). The component bones of the cervical spine are generally smaller than those of the thoracic spine, which are in turn smaller than those of the lumbar region. The sacral region connects laterally to the pelvis. While the sacral region is an integral part of the spine, for the purposes of fusion surgeries and for this disclosure, the word spine shall refer only to the cervical, thoracic, and lumbar regions.
[0003] The spinal column of bones is highly complex in that it includes over twenty bones coupled to one another, housing and protecting critical elements of the nervous system having innumerable peripheral nerves and circulatory bodies in close proximity. In spite of these complications, the spine is a highly flexible structure, capable of a high degree of curvature and twist in nearly every direction.
[0004] Genetic or developmental irregularities, trauma, chronic stress, tumors, and degenerative wear are a few of the causes which can result in spinal pathologies for which surgical intervention may be necessary. A variety of systems have been disclosed in the art which achieve immobilization and/or fusion of adjacent bones by implanting artificial assemblies in or on the spinal column. The region of the back which needs to be immobilized, as well as the individual variations in anatomy, determine the appropriate surgical protocol and implantation assembly. With respect to the failure of the intervertebral disc, the interbody fusion cage has generated substantial interest because it can be implanted laparoscopically into the anterior of the spine, thus reducing operating room time, patient recovery time, and scarification.
[0005] Referring now to FIGS. 1 and 2, in which a side perspective view of an intervertebral body cage and an anterior perspective view of a post implantation spinal column are shown, respectively, a more complete description of these devices of the prior art is herein provided. These cages 10 generally comprise tubular metal body 12 having an external surface threading 14 . They are inserted transverse to the axis of the spine 16 , into preformed cylindrical holes at the junction of adjacent vertebral bodies (in FIG. 2 the pair of cages 10 are inserted between the fifth lumbar vertebra (L 5 ) and the top of the sacrum (S 1 ). Two cages 10 are generally inserted side by side with the external threading 14 tapping into the lower surface of the vertebral bone above (L 5 ), and the upper surface of the vertebral bone (S 1 ) below. The cages 10 include holes 18 through which the adjacent bones are to grow. Additional material, for example bone graft materials, may be inserted into the hollow interior 20 of the cage 10 to incite or accelerate the growth of the bone into the cage. End caps (not shown) are often utilized to hold the bone graft material within the cage 10 .
[0006] These cages of the prior art have enjoyed medical success in promoting fusion and grossly approximating proper disc height. It is, however, important to note that the fusion of the adjacent bones is an incomplete solution to the underlying pathology as it does not cure the ailment, but rather simply masks the pathology under a stabilizing bridge of bone. This bone fusion limits the overall flexibility of the spinal column and artificially constrains the normal motion of the patient. This constraint can cause collateral injury to the patient's spine as additional stresses of motion, normally borne by the now-fused joint, are transferred onto the nearby facet joints and intervertebral discs. It would therefore, be a considerable advance in the art to provide an implant assembly which does not promote fusion, but, rather, which nearly completely mimics the biomechanical action of the natural disc cartilage, thereby permitting continued normal motion and stress distribution.
[0007] It is, therefore, an object of the present invention to provide a new and novel intervertebral spacer which stabilizes the spine without promoting a bone fusion across the intervertebral space.
[0008] It is further an object of the present invention to provide an implant device which stabilizes the spine while still permitting normal motion.
[0009] It is further an object of the present invention to provide a device for implantation into the intervertebral space which does not promote the abnormal distribution of biomechanical stresses on the patient's spine.
[0010] Other objects of the present invention not explicitly stated will be set forth and will be more clearly understood in conjunction with the descriptions of the preferred embodiments disclosed hereafter.
SUMMARY OF THE INVENTION
[0011] The preceding objects of the invention are achieved by the present invention which is a flexible intervertebral spacer device comprising a pair of spaced apart base plates, arranged in a substantially parallel planar alignment (or slightly offset relative to one another in accordance with proper lordotic angulation) and coupled to one another by means of a spring mechanism. In particular, this spring mechanism initially provides a weak restoring force when a compressive load is applied to the plates, but which restoring force becomes increasingly stronger as the compressive load increases. The spring mechanism may also permit limited rotation of the two plates relative to one another. While there are a wide variety of embodiments contemplated, the principle embodiment described herein includes a spiral-shaped wave washer having a radially diminishing amplitude.
[0012] More particularly, with respect to the base plates, which are similar in all embodiments, as the assembly is to be positioned between the facing surfaces of adjacent vertebral bodies, and as such need to have substantially flat external surfaces which seat against the opposing bone surfaces. Inasmuch as these bone surfaces are often concave, it is anticipated that the opposing plates may be convex in accordance with the average topology of the spinal anatomy. In addition, the plates are to mate with the bone surfaces in such a way as to not rotate relative thereto. (The plates rotate relative to one another, but not with respect to the bone surfaces to which they are each in contact with.) In order to prevent rotation of a plate relative to the bone, the upper and lower plates may each include outwardly directed spikes which penetrate the bone surface and mechanically hold the plates in place. Alternatively, the base plates may be coupleable to other securing means for holding the present invention in place.
[0013] It is further anticipated that the plates may include a porous coating into which the bone of the vertebral body can grow. (Note that this limited fusion of the bone to the base plate does not extend across the intervertebral space.)
[0014] Between the base plates, on the exterior of the device, there is included a circumferential wall which is resilient and which simply prevents vessels and tissues from growing into the interior of the device. This resilient wall may comprise a porous fabric or a semi-impermiable elastomeric material, and serves a similar purpose to the naturally occurring annulus material which surrounds the cartilage of the intervertebral disc, which the present invention is designed to replace when conditions warrant. Suitable tissue compatible materials meeting the simple mechanical requirements of flexibility and durability are prevalent in a number of medical fields including cardiovascular medicine, wherein such materials are utilized for venous and arterial wall repair, or for use with artificial valve replacements. Alternatively, suitable plastic materials are utilized in the surgical repair of gross damage to muscles and organs. Still further materials which could be utilized herein may be found in the field of orthopaedic in conjunction with ligament and tendon repair. It is anticipated that future developments in this area will produce materials which are compatible for use with this invention, the breadth of which shall not be limited by the choice of such a material.
[0015] As introduced above, the internal structure of the present invention comprises a force restoring member, which provides a restoring force of variable strength when compressed. More particularly, it is desirable that the restoring force, which is directed outward against the opposing plates, initially be lax, becoming more stiff as the applied compressive load becomes more intense. This feature imbues the spring mechanism with substantially better anatomical performance characteristics than other spring mechanisms previously contemplated.
[0016] In addition, in certain preferred embodiments, the restoring force providing subassembly does not substantially interfere with the rotation of the opposing plates relative to one another. Alternatively, the base plates may be selectively securable to the washer in such a way that it substantially inhibit any rotation of the plates. These alternate rotational capabilities, which are both described hereinbelow, do not materially affect the performance of the spring mechanism.
[0017] As further mentioned above, the force restoring member comprises at least one spiral-shaped wave washer having a radially diminishing amplitude. More particularly, wave washers resemble simple round washers which comprise a flat round ring, except that band of material which forms the washer rises and falls in a wave-like undulation around its circumferential edge. Stated alternatively, a standard washer is a relatively planar ring-shaped object, confined to the x-y plane. In the present invention, the wave washer is spiral-shaped in that it sweeps out an angle greater than 360 degrees and has an ever increasing radius. In the case of the spiral-shaped wave washer of the present invention, the amplitude of the undulations also decreases in the radial direction. The wave washer, thereby, takes on the appearance of a spiral galaxy, having a thicker central disc, and a flatter edge.
[0018] In as much as the restoring force of a wave washer is proportional to the elastic properties of the material and the amount of material being deformed, the magnitude of the restoring force provided by the wave washer may be modified by altering the thickness of the material in its radial extent, or in its z-axis. In the case of the spiral-shaped wave washer of radially diminishing amplitude, a varying restoring force is realized as the number of spirals of the spring which are engaged increases (as the base plates compress toward each other the spirals of lesser amplitude are progressively deflectively engaged). (For the purposes of this description, the top and the bottom of a wave washer shall be defined as the planes defined by the highest and lowest points of the circumferential undulations, respectively.)
[0019] As a compressive load is applied by a pair of plates against the top and bottom of a wave washer, the forces are first directed against the arches of the undulating waves at the center of the spiral, and are increasingly directed against the arches of the outer “rings”. These loads are also translated into a hoop stress which tends to radially expand the spirals of the washer in its x-y plane. This force of deflection against the arches, and the hoop stress in the radial direction, are counterbalanced by the material strength of the washer. The strain of the material causes a deflection in the height of the washer and a slight radial expansion. Stated equivalently, a wave washer responds to a compressive load by deflecting compressively in z-axis, radially, and circumferentially.
[0020] In general, the spiral wave washer is one of the strongest configurations for a spring, and is highly suitable for use as a restoring force providing subassembly for use in an intervertebral spacer element which must endure considerable cyclical loading in an active human adult.
[0021] In a preferred embodiment of the present invention, a simple screw locks one of the ends of the washer to the base plate.
[0022] Finally, inasmuch as the human body has a tendency to produce fibrous tissues in perceived voids, such as may be found within the interior of the present invention, and such fibrous tissues may interfere with the stable and/or predicted functioning of the device, preferred embodiments of the present invention may be filled with a highly resilient elastomeric material. The material itself should be highly biologically inert, and should not substantially interfere with the restoring forces provided by the spring mechanisms therein. Suitable materials may include hydrophilic monomers such as are used in contact lenses. Alternative materials include silicone jellies and synthetic collagens such as have been used in cosmetic applications. As with the exterior circumferential wall, which was described above as having a variety of suitable alternative materials, it is anticipated that future research will produce alternatives to the materials described herein, and that the future existence of such materials which may be used in conjunction with the present invention shall not limit the breadth thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] [0023]FIG. 1 is a side perspective view of an interbody fusion device of the prior art;
[0024] [0024]FIG. 2 is a front view of the anterior portion of the lumbo-sacral region of a human spine, into which a pair of interbody fusion devices of the type shown in FIG. 1 have been implanted;
[0025] [0025]FIGS. 3 a and 3 b are side cross-section views of the upper and lower opposing plates of the present invention;
[0026] [0026]FIG. 4 is a side cross-section view of the opposing plates in association with one another, wherein an exterior skirt is included;
[0027] [0027]FIG. 5 is a side perspective view of a spiral-shaped wave washer having a radially diminishing amplitude of the type which is utilized in conjunction with the present invention; and
[0028] [0028]FIG. 6 is a side cross-section view of an embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0029] While the present invention will be described more fully hereinafter with reference to the accompanying drawings, in which particular embodiments and methods of implantation are shown, it is to be understood at the outset that persons skilled in the art may modify the invention herein described while achieving the functions and results of this invention. Accordingly, the descriptions which follow are to be understood as illustrative and exemplary of specific structures, aspects and features within the broad scope of the present invention and not as limiting of such broad scope. Like numbers refer to similar features of like elements throughout.
[0030] Referring now to FIGS. 3 a and 3 b , side cross-section views of the top and bottom plate members 100 a 100 b of a first embodiment of the present invention is shown. More particularly, in this embodiment, the upper and lower plates 100 a , 100 b are substantially identical. As the device is designed to be positioned between the facing surfaces of adjacent vertebral bodies, the plates include substantially flat surface portions 102 a , 102 b which seat against the opposing bone surfaces. In addition, the plates are to mate with the bone surfaces in such a way as to not rotate relative thereto. It is, therefore, preferred that the plates should include a porous coating 104 a , 104 b into which the bone of the vertebral body can grow. (Note that this limited fusion of the bone to the base plate does not extend across the intervertebral space.) An additional threaded hole 106 a , 106 b is provided in each plate such that the interior of the device may be readily accessed if a need should arise.
[0031] The plates 100 a , 100 b further include a circumferential flange 108 a , 108 b . The flange 108 a , 108 b may be offset with respect to the front 110 a , 110 b and rear 111 a , 111 b orientation of the overall assembly. More particularly, the offset nature of the flanges 108 a , 108 b is exhibited in the non-symmetric appearance of each flange as it circumscribes the corresponding plate 100 a , 100 b . By this it is meant that the portion of the flange 108 a, 108 b which corresponds to the rear 111 a , 111 b of the device is shorter than the portion corresponding to the front 110 a , 110 b of the device.
[0032] Referring now to FIG. 4, a partially assembled embodiment of the present invention is provided in a side cross-section view, wherein the upper and lower plates 100 a , 100 b illustrated in FIGS. 3 a and 3 b are joined by means of a circumferential wall 120 . More particularly, between the base plates 100 a , 100 b , on the exterior of the device, there is included a circumferential wall 120 which is resilient and which is provided to prevents vessels and tissues from entering within the interior of the device. It is preferred that the resilient wall 120 comprise a porous fabric or a semi-impermiable elastomeric material. The wall 120 is further designs to couple to the flanges 108 a , 108 b of the corresponding plates 100 a , 100 b.
[0033] Referring now to FIG. 5, the spiral-shaped radially diminishing amplitude force restoring element which comprises a component of the present invention is provided in a perspective view. More particularly, a wave washer 130 is so named inasmuch as it is comprised of a curved band of material (a titanium alloy or stainless steel is preferable, although other suitable surgical materials may be found to function adequately), which band rises and falls in an undulating wave-like conformation 132 . In the case of a spiral wave washer, the curvature begins in a tightly wound center and expands outward as a spiral. The periodic arches 134 and valleys 136 provide the wave. In the spiral wave washer of the present invention, amplitude of the waves at the center of the washer are greater than the amplitude at the outer regions, such that a compressive load applied to the washer is initially borne by the central, larger waves, and only as the washer is heavily loaded do the outer waves become engaged.
[0034] More particularly, the restoring force of a wave washer of the type illustrated in FIG. 5 is proportional to the elastic properties of the material. As a compressive load is applied to the washer by the opposing plates, the forces are directed down onto the arches 134 and up against the valleys 136 . The first arches and valleys to be engaged provide a limited opposing (i.e. restoring) force. As the load continues to increase, a larger portion of the spiral is engaged, thereby causing the restoring force to climb substantially. This is a much more anatomically accurate response.
[0035] As the loading is applied, a significant fraction of these compressive forces are immediately translated into quasi-hoop stresses which radially expanding the washer. This hoop stress is also counterbalanced by the material strength of the washer. Unlike a continuous ring-shaped washer (which has a very high stress to deflection ratio), a spiral-shaped wave washer deflects circumferentially (this is characteristic of a much lower stress to deflection ratio). However, the increased number of waves which must be engaged as the deflection increases provides greater resistance as the washer is heavily compressed.
[0036] Referring now to FIGS. 3, 5 and 6 , the means for securing the spiral-shaped radially diminishing amplitude wave washer is now described. The innermost end 157 of the spiral band of the wave washer includes a threaded hole 159 which aligns with the threaded hole 106 a or 106 b in the base plate to which it is to be secured. A screw 161 shown in FIG. 6 secures the washer to the base plate through the aligned holes.
[0037] Referring now specifically to FIG. 6, an integrated device embodying the principles of the present invention is provided in a side cross-section view. The base plates 100 a , 100 b are disposed in a spaced apart relationship such that the opposing inner surfaces are approximately parallel and facing one another. A single spiral-shaped radially diminishing amplitude wave washer 130 is disposed between the plates, and retained therein by the circumferential flanges 108 a , 108 b . The spiral-shaped radially diminishing amplitude wave washer 130 is constrained against rotational motion by a screw 161 . A flexible circumferential skirt 120 is provided around the entirety of the device, such that the tissue of the patient may not grow into, and thereby cause pain, or inhibit the functionality of the device. It shall be understood that the securing screw does not prevent the plates from rotating relative to one another.
[0038] In an alternate embodiment, the spiral wave washer can be secured to both plates (at separate points along its spiral shape) and thereby substantially restrain the plates from rotating relative to one another.
[0039] In both embodiments, however, the flexible circumferential skirt 120 , which is provided around the entirety of the device will inhibit some rotation, but is principally provided such that the tissue of the patient may not grow into, and thereby cause pain, or inhibit the functionality of the device.
[0040] While there have been described and illustrated embodiments of an intervertebral spacer device utilizing a spiral-shaped radially diminishing amplitude wave washer force restoring element, it will be apparent to those skilled in the art that variations and modifications are possible without deviating from the broad spirit and principle of the present invention. The present invention shall, therefore, be limited only to the full scope of the claims allowable in light of the disclosures made herein, and in the parallel reference incorporated herein by reference.
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An intervertebral spacer device having a pair of opposing plates for seating against opposing vertebral bone surfaces, separated by at least one force restoring element. The preferred force restoring mechanism is a spiral-shaped radially diminishing amplitude wave washer.
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[0001] This application claims priority benefit to U.S. Provisional Patent Application 61/973,894 filed Apr. 2, 2014 and U.S. Provisional Patent Application 61/974,529 filed Apr. 3, 2014, the contents of all of which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to compositions rice seed treatment. More specifically the invention relates to compositions for treating rice seed grown in zinc-deficient conditions.
BACKGROUND OF THE INVENTION
[0003] All crop plants require certain fundamental components for growth, but many areas where it is desirable to grow crops have shortcomings. By developing technologies to compensate for insufficient or missing natural components, flexibility increases regarding which crops are grown and where they are grown. For example, crops with moderate to high moisture requirements can grow in arid climates if irrigation is provided. Enhancements need not always be on a permanent basis, though. Where one crop has depleted a certain soil nutrient during a growing season, in the subsequent season that nutrient can be supplemented to reinstate the natural or optimum levels available to the new season's crop.
[0004] Regarding rice, a challenge when striving for optimum production is to ensure sufficient zinc is available to the plant. A rate of about 3-20 ppm can be sufficient. But some areas where rice is grown have soil which is naturally low or deficient in zinc. In other cases, due to crop rotation or environmental factors, there is a temporary lower level of zinc available to the rice plants. By offering supplemental zinc to the plant or growing media the maximum crop growth and yield potential can be achieved.
[0005] Commercially available zinc products for rice are typically applied to the soil or to the growing plant as a foliar application. However under some circumstances it can be preferred to provide the zinc directly on the rice seed. Zinc oxide (ZnO) or Zinc sulfate (ZnSO 4 ) are known for this purpose.
[0006] Ethylenediaminetetraacetic acid (EDTA) is a chelating agent, which readily binds to metal ions and can be used to keep divalent or polyvalent metals ions in solutions. In agriculture the chelate with zinc, ZnEDTA is known to be mixed with other nutrients and/or fertilizers and applied as part of a drip irrigation system (CN 102964163) or via foliar application (CN 101391927).
[0007] Slaton et al disclose the application of ZnEDTA to rice seed and recommend between 2.2 and 5.8 g Zn/kg of rice seed as an economical alternative to soil-applied zinc. In their trials 1.4 g ZnEDTA/kg rice seed was not successful (Evaluation of Zinc Seed Treatments for Rice, Agron. J. 93(1):152-157 (2001)).
[0008] Despite the existing technologies, there remains a need in the art for improved compositions to provide optimum zinc levels to rice plants.
SUMMARY OF THE INVENTION
[0009] It is therefore an object of the present invention to provide an improved zinc-containing rice seed treatment composition. Methods to improve rice growth using the composition are also provided.
[0010] The present invention surprisingly provides zinc as a micronutrient in the form of ZnEDTA at very low levels compared with commercial standards and the teachings of the prior art. This can help prevent unnecessary excess of zinc in the environment, and prevent unnecessary costs associated with overuse of zinc.
[0011] In a first aspect, the present invention provides a rice seed treatment composition comprising zinc in the form of zinc ethylenediaminetetraacetic acid, wherein the composition is applied to rice seed at a rate of 1-2 g Zn/kg rice seed, excepted is a rate of 1.40 g Zn/kg rice seed. The seed treatment composition can be applied to rice seed at a rate of 1.10-1.90 g Zn/kg rice seed, preferably 1.20-1.80 g Zn/kg rice seed, most preferably 1.3-1.7 g Zn/kg rice seed. The composition can further comprise a pesticidal active ingredient, for example thiamethoxam, clothianidin, imidacloprid, acetamiprid, dinotefuran, nitenpyram, thiacloprid, thiodicarb, aldicarb, carbofuran, furadan, fenoxycarb, carbaryl, sevin, ethienocarb, fenobucarb, chlorantraniliprole, cyantraniliprole, flubendiamide, spinosad, spinetoram, lambda-cyhalothrin, gamma-cyhalothrin, tefluthrin, fipronil, sulfoxaflor, azoxystrobin, trifloxystrobin, fluoxastrobin, cyproconazole, difenoconazole, prothioconazole, tebuconazole, triticonazole, fludioxonil, thiabendazole, ipconazole, cyprodinil, myclobutanil, metalaxyl, metalaxyl-M, sedaxane, penflufen, abamectin, aldicarb, thiadicarb, carbofuran, carbosulfan, oxamyl, aldoxycarb, ethoprop, methomyl, benomyl, alanycarb, iprodione, phenamiphos (fenamiphos), fensulfothion, terbufos, fosthiazate, dimethoate, phosphocarb, dichlofenthion, isamidofos, fosthietan, isazofos ethoprophos, cadusafos, terbufos, chlorpyrifos, dichlofenthion, heterophos, isamidofos, mecarphon, phorate, thionazin, triazophos, diamidafos, fosthietan, phosphamidon, imicyafos, captan, thiophanate-methyl and/or thiabendazole.
[0012] In another aspect, the invention provides a method of improving the growing characteristics of rice which comprises applying ZnEDTA to rice seeds at a rate of 1-2 g Zn/kg rice seed and sowing the seeds, wherein the rate is not 1.40 g Zn/kg rice seed. The seeds can be sown in zinc-deficient soil. At least one pesticidal active ingredient could be applied to the rice seeds prior to the sowing step. Examples of suitable pesticidal agents include thiamethoxam, clothianidin, imidacloprid, acetamiprid, dinotefuran, nitenpyram, thiacloprid, thiodicarb, aldicarb, carbofuran, furadan, fenoxycarb, carbaryl, sevin, ethienocarb, fenobucarb, chlorantraniliprole, cyantraniliprole, flubendiamide, spinosad, spinetoram, lambda-cyhalothrin, gamma-cyhalothrin, tefluthrin, fipronil, sulfoxaflor, azoxystrobin, trifloxystrobin, fluoxastrobin, cyproconazole, difenoconazole, prothioconazole, tebuconazole, triticonazole, fludioxonil, thiabendazole, ipconazole, cyprodinil, myclobutanil, metalaxyl, metalaxyl-M, sedaxane, penflufen, abamectin, aldicarb, thiadicarb, carbofuran, carbosulfan, oxamyl, aldoxycarb, ethoprop, methomyl, benomyl, alanycarb, iprodione, phenamiphos (fenamiphos), fensulfothion, terbufos, fosthiazate, dimethoate, phosphocarb, dichlofenthion, isamidofos, fosthietan, isazofos ethoprophos, cadusafos, terbufos, chlorpyrifos, dichlofenthion, heterophos, isamidofos, mecarphon, phorate, thionazin, triazophos, diamidafos, fosthietan, phosphamidon, imicyafos, captan, thiophanate-methyl and thiabendazole.
[0013] In another aspect, the invention provides a rice seed comprising ZnEDTA at a rate of from 1 to 2 g Zn/kg rice seed, wherein the rate is not 1.40 g Zn/kg rice seed. The rice seed may further comprise thiamethoxam, fludioxonil, azoxystrobin, metalaxyl-M and/or sedaxane.
[0014] As used herein “rice” refers to the cereals scientifically classified as rice such as Oryza glaberrima, O. nivara, O. rufipogon and O. sativa and also plants which are commonly referred to as rice for example Zizania spp.
[0015] The rice discussed herein is to be understood as being those crops which are naturally occurring, obtained by conventional methods of breeding, or obtained by genetic engineering. They include crops which contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
[0016] Rice crops are to be understood as also including those crops which have been rendered tolerant to herbicides like bromoxynil or classes of herbicides such as ALS-, EPSPS-, GS-, HPPD- and PPO-inhibitors. Crops are also to be understood as being those which naturally are or have been rendered resistant to harmful insects. This includes plants transformed by the use of recombinant DNA techniques, for example, to be capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria. Examples of toxins which can be expressed include δ-endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonising nematodes, and toxins produced by scorpions, arachnids, wasps and fungi. Crops or seed material thereof can also be resistant to multiple types of pests (so-called stacked transgenic events when created by genetic modification). For example, a plant can have the ability to express an insecticidal protein while at the same time being herbicide tolerant.
[0017] As used herein, the term “seed” refers to any suitable plant propagation material and specifically includes seeds in the strict sense as well as vegetative material of plants such as synthetic seeds created using tissue culture.
[0018] As used herein, ‘improving the growth’ can mean for example an increase in germination, more consistent germination, increase in yield, improvement in plant vigour, and/or an improvement in plant quality.
[0019] The term “increase in yield” means that the yield of a product of the plant is increased by a measurable amount over the yield of the same product of the plant produced under the same conditions, but without the application of the composition according to the present invention. It is preferred that the yield is increased by at least about 1%, preferably 2%, more preferably 3%, yet more preferably 4% or more. Even more preferred is an increase in yield of at least about 5%, 10%, 15% or 20% or more.
[0020] As used herein, an ‘improvement in plant vigour’ means that certain traits are improved qualitatively or quantitatively when compared with the same trait in a control plant which has been grown under the same conditions in the absence of the method of the invention. Such traits include, but are not limited to, early and/or improved germination, improved emergence, the ability to use less seeds, increased root growth, a more developed root system, increased root nodulation, increased shoot growth, increased tillering, stronger tillers, more productive tillers, increased or improved plant stand, less plant verse (lodging), an increase and/or improvement in plant height, an increase in plant weight (fresh or dry), bigger leaf blades, greener leaf colour, increased pigment content, increased photosynthetic activity, earlier flowering, longer panicles, early grain maturity, increased seed, fruit or pod size, increased pod or ear number, increased seed number per pod or ear, increased seed mass, enhanced seed filling, less dead basal leaves, delay of senescence, improved vitality of the plant, increased levels of amino acids in storage tissues and/or less inputs needed (e.g. less fertiliser, water and/or labour needed). A plant with improved vigour may have an increase in any of the aforementioned traits or any combination or two or more of the aforementioned traits.
[0021] As used herein, an ‘improvement in plant quality’ means that certain traits are improved qualitatively or quantitatively when compared with the same trait in a control plant which has been grown under the same conditions in the absence of the method of the invention. Such traits include, but are not limited to, improved visual appearance of the plant, improved quality of harvested material (such improved quality may manifest as improved visual appearance of the harvested material), improved carbohydrate content (e.g. increased quantities of sugar and/or starch, improved sugar acid ratio, reduction of reducing sugars, increased rate of development of sugar), improved protein content, improved nutritional value, reduction in anti-nutritional compounds, improved organoleptic properties (e.g. improved taste) and/or improved consumer health benefits (e.g. increased levels of vitamins and anti-oxidants)), improved post-harvest characteristics (e.g. enhanced shelf-life and/or storage stability, easier processability, easier extraction of compounds), more homogenous crop development (e.g. synchronised germination, flowering and/or fruiting of plants), and/or improved seed quality (e.g. for use in following seasons). A plant with improved quality may have an increase in any of the aforementioned traits or any combination or two or more of the aforementioned traits.
DETAILED DESCRIPTION OF THE INVENTION
[0022] Although the breakthrough of the present invention is to provide an improved rice seed treatment composition for increasing available zinc to the rice plant, it will be appreciated by skilled persons that the composition may be used individually or in combination with other agents appropriate for use as a rice seed treatment.
[0023] Rice seeds treated with the composition of the invention may further include an agrochemical applied simultaneously or separately. Such agrochemicals can include fungicides, insecticides, bactericides, acaricides, nematicides, nutrients, fertilizers, and/or plant growth regulators. These agents may be provided as formulations comprising, inter alia, carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation. The present invention is also suitable for use with other agrochemicals such as primers and safeners.
[0024] Examples of suitable agrochemicals include the following:
[0025] Insecticides such as benzoylureas, carbamates, chloronicotinyls, diacylhydrazines, diamides, fiproles, macrolides, neonicotinoids, nitroimines, nitromethylenes, organochlorines, organophosphates, organosilicons, organotins, phenylpyrazoles, phosphoric esters, pyrethroids, spinosyns, tetramic acid derivatives and tetronic acid derivatives.
[0026] Specific examples of preferred insecticides include thiamethoxam, clothianidin, imidacloprid, acetamiprid, dinotefuran, nitenpyram, thiacloprid, thiodicarb, aldicarb, carbofuran, furadan, fenoxycarb, carbaryl, sevin, ethienocarb, fenobucarb, chlorantraniliprole, cyantraniliprole, flubendiamide, spinosad, spinetoram, lambda-cyhalothrin, gamma-cyhalothrin, tefluthrin, fipronil, and sulfoxaflor.
[0027] Fungicides such as acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, anilide fungicides, antibiotic fungicides, aromatic fungicides, arsenical fungicides, aryl phenyl ketone fungicides, benzamide fungicides, benzanilide fungicides, benzimidazole fungicides, benzothiazole fungicides, botanical fungicides, bridged diphenyl fungicides, carbamate fungicides, carbanilate fungicides, conazole fungicides, copper fungicides, dicarboximide fungicides, dinitrophenol fungicides, dithiocarbamate fungicides, dithiolane fungicides, furamide fungicides, furanilide fungicides, hydrazide fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, organophosphorous fungicides, organotin fungicides, oxathiin fungicides, oxazole fungicides, phenylsulfamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, strobilurin fungicides, sulfonanilide fungicides, thiadiazole fungicides, thiazole fungicides, thiazolidine fungicides, thiocarbamate fungicides, thiophene fungicides, triazine fungicides, triazole fungicides, triazolopyrimidine fungicides, urea fungicides, valinamide fungicides, and zinc fungicides.
[0028] Specific examples of preferred fungicides include azoxystrobin, trifloxystrobin, fluoxastrobin, cyproconazole, difenoconazole, prothioconazole, tebuconazole, triticonazole, fludioxonil, thiabendazole, ipconazole, cyprodinil, myclobutanil, metalaxyl, metalaxyl-M (also known as mefenoxam), sedaxane, and penflufen.
[0029] Nematicides such as antibiotic nematicides, avermectin nematicides, botanical nematicides, carbamate nematicides, oxime carbamate nematicides, and organophosphorus nematicides.
[0030] Specific examples of preferred nematicides include abamectin, aldicarb, thiadicarb, carbofuran, carbosulfan, oxamyl, aldoxycarb, ethoprop, methomyl, benomyl, alanycarb, iprodione, phenamiphos (fenamiphos), fensulfothion, terbufos, fosthiazate, dimethoate, phosphocarb, dichlofenthion, isamidofos, fosthietan, isazofos ethoprophos, cadusafos, terbufos, chlorpyrifos, dichlofenthion, heterophos, isamidofos, mecarphon, phorate, thionazin, triazophos, diamidafos, fosthietan, phosphamidon, imicyafos, captan, thiophanate-methyl and thiabendazole.
[0031] Nematicidally active biological agents include any biological agent that has nematicidal activity and could be used with the present invention. The biological agent can be any type known in the art including bacteria and fungi. The wording “nematicidally active” refers to having an effect on, such as reduction in damage caused by, agricultural-related nematodes. Examples of nematicidally active biological agents include Bacillus firmus, B. cereus, B. subtilis, Pasteuria penetrans, P. nishizawae, P. ramosa, P. thornei , and P. usgae . A suitable Bacillus firmus strain is strain CNCM 1-1582 which is commercially available as BIONEM. A suitable Bacillus cereus strain is strain CNCM 1-1562. Of both Bacillus strains more details can be found in U.S. Pat. No. 6,406,690.
[0032] Agrochemicals referred to herein using their common name are known, for example, from “The Pesticide Manual”, 15th Ed., British Crop Protection Council 2009.
[0033] As noted above the agrochemicals of the invention may be provided in the form of formulated products. There can be many purposes for doing so, and for each a different component might be added. For example, it might be desired to protect rice seed during storage and transport from any toxicity issues associated with close physical proximity to an agrochemical. Many other purposes and solutions will be apparent to the skilled person.
[0034] Other additives which are used with seeds may advantageously be provided in conjunction with the present invention. Such additives include, but are not limited to, uv-protectants, colorants, brighteners, pigments, dyes, extenders, dispersing agents, excipients, anti-freeze agents, herbicidal safeners, seed safeners, seed conditioners, micronutrients, fertilizers, surfactants, sequestering agents, plasticizers, polymers, emulsifiers, flow agents, coalescing agents, defoaming agents, humectants, thickeners, and waxes. Such additives are commercially available and known in the art.
[0035] Methods for applying or treating active ingredients on to plant propagation material are known in the art and include dressing, coating, pelleting and soaking application methods. Conventional treating techniques and machines can be used, such as fluidized beds, roller mills, rotostatic seed treaters, drum coaters, and spouted beds. Also, using commercially available equipment (Van der Ende PHYTO-DRIP BV, NL) it is possible to perform a precise seed soaking application at the time of planting.
[0036] Examples of seed treatment formulation types for pre-mix compositions include:
[0000] WS: wettable powders for seed treatment slurry
LS: solution for seed treatment
ES: emulsions for seed treatment
FS: suspension concentrate for seed treatment
WG: water dispersible granules, and
CS: aqueous capsule suspension.
[0037] The Examples which follow serve to illustrate the invention.
Formulation Examples
[0038]
[0000] Powders for dry seed treatment a) b) c) active ingredients 25% 50% 75% light mineral oil 5% 5% 5% highly dispersed silicic acid 5% 5% — Kaolin 65% 40% — Talcum — 20
The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
[0000] Dusts a) b) c) Active ingredients 5% 6% 4% Talcum 95% — — Kaolin — 94% — mineral filler — — 96%
Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill. Such powders can be used for dry dressings for seed.
Suspension Concentrate
[0039]
[0000] active ingredients 40% propylene glycol 10% nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6% Sodium lignosulfonate 10% Carboxymethylcellulose 1% silicone oil (in the form of a 75% emulsion in water) 1% Water 32%
The finely ground combination is mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with e.g. water. Using such dilutions, seeds can be treated by spraying, pouring or immersion.
Flowable Concentrate for Seed Treatment
[0040]
[0000] active ingredients 40% propylene glycol 5% copolymer butanol PO/EO 2% Tristyrenephenole with 10-20 moles EO 2% 1,2-benzisothiazolin-3-one (in the form of a 20% solution 0.5% in water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in water) 0.2% Water 45.3%
The finely ground combination is mixed with the adjuvants, giving a flowable concentrate from which suspensions of any desired dilution can be obtained by dilution with e.g. water. Using such dilutions, seeds can be treated by spraying, pouring or immersion.
Biological Example
Evaluation of Benefits of Inventive Composition
[0041] In order to evaluate advantages of the inventive composition versus known technologies, an in-vivo evaluation was performed involving treatments with three different forms of zinc on rice seed.
[0042] For the inventive composition, ZnEDTA (in the form of Dissolvine E-Zn-15 having 3% free zinc, Akzo Nobel, IL., USA) was applied as a 20% w/w aqueous solution at rates of 1.18 1.47 and 1.76 g ZnEDTA/kg seed. This was accomplished by using 8, 10 or 12 fl oz per cwt.
[0043] For the first comparative composition, ZnSO 4 was applied as a 24.7% solution at a rate of 1.90 g ZnSO 4 /kg seed (in the form of ZINC PLUS having 10% free zinc, DeltAg, MS, USA). This was accomplished by using 10 fl oz per cwt.
[0044] For the second comparative composition, ZnO was applied as a 32.50% aqueous suspension at a rate of 2.00 g ZnO/kg seed (in the form of ZINCHE ST having 26% free zinc, Drexel Chemical Co, TN, USA). This was accomplished by using 8 fl oz per cwt.
[0045] To ensure pest and disease pressure did not affect the results, the seeds from all test groups were also treated with a conventional insecticide and fungicide mixture. This was done by preparing a mixture of each zinc-containing compound with the insecticide/fungicide mixture and adding water to make a total of 25 fl oz per ctw (thiamethoxam at 1.80 g/kg seed, fludioxonil at 0.015 g/kg seed, azoxystrobin at 0.07 g/kg seed, metalaxyl-M at 0.09 g/kg seed and sedaxane at 0.01 g/kg seed; commercial products available as e.g. CRUISER MAXX and VIBRANCE, both Syngenta Crop Protection, NC, USA). Also evaluated were untreated control and seeds having only the conventional insecticide and fungicide treatment.
[0046] For all test groups, one (1) kg batches of rice seed variety CL 151 (Clearfield Seed, Horizon Ag, TN, USA) were treated on a Hege seed treater (Wintersteiger AG, Austria) using a standard protocol. The seeds were allowed to dry.
[0047] Standard commercial greenhouse containers, 10 cm diameter by 9 cm deep, were filled with 350 cc of a rooting media mix consisting of 33% (v/v) Zn deficient soil collected in Arkansas, USA and then sterilized in an autoclave and 66% (v/v) commercial planting mix (NB peat, Fafard, MA, USA). Analysis of the potting mix confirmed that the zinc levels were low, at 1.97 ppm and pH levels were <7.
[0048] Prior to planting the soil was moistened with 200 ml tap water per pot. Eight seeds were sown per pot by placing them on soil surface then lightly covering with 0.5 cm of loose peat. Each treatment group had six replicates. Pots were transferred to greenhouse and maintained at 30/24° C. day/night temperature with 16 hours of supplemental high pressure sodium light. All pots were lightly watered manually every 2 to 3 days to prevent dehydration of the germination zone.
[0049] Ten days after planting (10 DAP) a drip irrigation emitter was installed on each pot. The irrigation system was set to deliver 100 ml of tap water each morning and again each evening. Germination rates were recorded and at 11 DAP rice seedlings were thinned to 5 plants per pot. By 17 DAP rice plants were in the V3 growth stage. At 18 DAP nitrogen fertilizer (urea) was added to the irrigation water at 200 ppm for the duration of trial. At 22 DAP rice plants were in the V4 growth stage with first tiller forming.
[0050] At 29 DAP rice plants were in the V5 growth stage with 3 tillers. The above ground plant tissue was harvested and placed in paper bags. Bags were placed in an oven set at 100° C. for 72 hours to dry. The dry tissue was removed from the bags and weighed. Samples of the dry tissue were analyzed for total zinc uptake (MicroMacro International, Inc. Labs, GA, USA). The procedure used for drying was the Association of Official Agricultural Chemists (AOAC) procedure 922.02, that for the ash was AOAC procedure 930.05 and the analytical method was US EPA procedure 6010C. Results are shown in Table 1 below.
[0000]
TABLE 1
Trial results
Treatment
(g Zn complex/kg seed)
Germination rate (%)
Zinc uptake (ppm)
Untreated
0
42
242.27
Insecticide and
0
Not recorded
250.33
fungicide only
ZnEDTA
1.18
Not recorded
275.47
1.47
45
304.74
1.76
Not recorded
316.00
ZnSO 4
1.90
43
237.50
ZnO
2.00
42
253.65
[0051] As is evident from the data, seeds treated with the inventive composition showed improved zinc update as compared to conventional products. This lead to improved germination and it is expected if the trial was allowed to run to harvest, an increased yield.
[0052] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the scope of the present invention.
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A rice seed treatment composition can comprise ZnEDTA. Methods of improving rice growing characteristics can involve treating rice seeds with ZnEDTA.
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CROSS REFERENCE TO RELATED APPLICATION
[0001] This Continuation application claims the benefit of U.S. Ser. No. 13/046,138 filed Mar. 11, 2011, now pending, which claims the benefit of application U.S. Ser. No. 10/968,481 filed Oct. 19, 2004, now abandoned, which claims the benefit of U.S. Provisional Application Ser. No. 60/513,886, now expired, the entire disclosure of which is herein incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention related to a process for making sterile aripiprazole of desired particle size distribution and mean particle size which is especially adapted for use in preparing a controlled release formulation which releases aripiprazole over at least one week or more.
BACKGROUND OF THE INVENTION
[0003] U.S. provisional application No. 60/513,618, discloses a controlled release sterile injectable aripiprazole formulation in the form of a sterile suspension, and a method for preparing a sterile freeze-dried aripiprazole formulation (employed in forming the injectable formulation) which includes the steps of:
[0004] (a) preparing sterile bulk aripiprazole preferably having a desired particle size distribution and mean particle size within the range from about 5 to about 100 microns, more preferably from about 10 to about 90 microns,
[0005] (b) preparing a sterile vehicle for the sterile bulk aripiprazole,
[0006] (c) combining the sterile bulk aripiprazole and the sterile vehicle to form a sterile primary suspension,
[0007] (d) reducing the mean particle size of aripiprazole in the sterile primary suspension to within the range from about 0.05 to about 30 microns, to form a final sterile suspension, and
[0008] (e) freeze drying the final sterile suspension to form a sterile freeze-dried suspension of the aripiprazole of desired polymorphic form (anhydrous, monohydrate, or a mixture of both).
[0009] In carrying out the above method for preparing the freeze-dried aripiprazole formulation, it is required that everything be sterile so that sterile aripiprazole and sterile vehicle are combined aseptically to form a sterile suspension and that the sterile suspension be freeze-dried in a manner to form sterile freeze-dried powder or cake. Thus, an aseptic procedure is employed to produce sterile bulk aripiprazole of desired mean particle size, and particle size distribution, by crystallization methods as opposed to ball milling. The sterile bulk aripiprazole preferably prepared in step (a) by means of the impinging jet crystallization method, has a desired small particle size and narrow particle size distribution, high surface area, high chemical purity, and high stability due to improved crystal structure.
[0010] The impinging jet crystallization utilizes two jet streams that strike each other head-on. One of the streams carries a solution rich in the aripiprazole and the other carries an anti-solvent, such as water. The two streams strike each other which allows for rapid homogeneous mixing and supersaturation due to high turbulence and high intensity of micromixing upon impact. This immediate achievement of supersaturation initiates rapid nucleation. In general, the average crystal size of the aripiprazole decreases with increasing supersaturation and decreasing temperature of the anti-solvent. Therefore, in order to obtain the smallest particle size, it is advantageous to have the highest possible concentration of the aripiprazole rich solution and the lowest temperature of the anti-solvent.
[0011] The technique employed for forming sterile bulk aripiprazole is important since particle size of the aripiprazole formulation controls its release profile in the blood system over a period of one month.
[0012] It has been found that batch crystallization of aripiprazole produces particles 100 microns. However, in formulating the controlled release sterile aripiprazole injectable formulation discussed above, the particle size of the aripiprazole needs to be 95% 100 microns. In addition, a narrow particle size distribution is needed to maintain control of the release profile. Milling of batch aripiprazole is undesirable, as a broad particle size distribution will be obtained. Thus, it would be advantageous to employ a technique for preparing sterile bulk aripiprazole which can reduce particle size of aripiprazole to 95% 100 microns with a narrower particle size distribution than attainable employing batch crystallization.
[0013] U.S. Pat. No. 5,006,528 to Oshiro et al. discloses 7-[(4-phenylpiperazino)-butoxy] carbostyrils, which include aripiprazole, as dopaminergic neurotransmitter antagonists.
[0014] Aripiprazole which has the structure
[0000]
[0000] is an atypical antipsychotic agent useful in treating schizophrenia. It has poor aqueous solubility (<1 μg/mL at room temperature).
[0015] U.S. Pat. No. 6,267,989 to Liversidge, et al. discloses a method for preventing crystal growth and particle aggregation in nanoparticulate compositions wherein a nanoparticulate composition is reduced to an optimal effective average particle size employing aqueous milling techniques including ball milling.
[0016] U.S. Pat. No. 5,314,506 to Midler, et al. discloses a process for the direct crystallization of a pharmaceutical having high surface area particles of high purity and stability wherein impinging jet streams are employed to achieve high intensity micromixing of particles of the pharmaceutical followed by nucleation and direct production of small crystals.
[0017] U.S. Pat. No. 6,302,958 to Lindrud et al. discloses a method and apparatus for crystallizing submicron-sized crystals of a pharmaceutical composition employing sonication to provide ultrasonic energy in the immediate vicinity of impinging fluid drug and solvent streams so as to effect nucleation and the direct production of small crystals.
[0018] U.S. application Ser. No. 10/419,418, filed Apr. 21, 2003 by Chenkou Wei (attorney docket TU58 NP) which is based on U.S. Provisional Applications Nos. 60/376,414, filed Apr. 29, 2002 and 60/439,066, filed Jan. 9, 2003 entitled “Crystallization System Using Atomization” discloses a method for crystallizing a pharmaceutical by atomizing one solution and introducing the atomized solution into a vessel containing a second solution where the solutions are mixed to form a product, which does not require post-crystallization milling. This application is incorporated herein by reference.
[0019] U.S. application Ser. No. 10/419,647, filed Apr. 21, 2003 by Chenkou Wei (attorney docket TU59 NP) which is based on U.S. Provisional Applications Nos. 60/379,351, filed May 10, 2002 and 60/439,057, filed Jan. 9, 2003 entitled “Crystallization System Using Homogenization” discloses a process for crystallizing a chemical material from a first solution and a second solution wherein the first solution is atomized and introduced into a second solution, and the atomized solution and second solution are mixed to form the product. This application is incorporated herein by reference.
BRIEF DESCRIPTION OF THE INVENTION
[0020] In accordance with the present invention, there is provided a process for preparing sterile bulk aripiprazole of desired small particle size and narrow particle size distribution, preferably having an average particle size less than about 100 microns but preferably greater than 25 microns, which includes the steps of:
[0021] (a) providing a jet stream of a solution of aripiprazole in an organic solvent, preferably ethanol, preferably heated at a desired elevated temperature;
[0022] (b) providing a jet stream of anti-solvent, preferably water, which is capable of initiating precipitation of aripiprazole from solution, preferably said anti-solvent being at a desired temperature below the temperature of the solution of aripiprazole;
[0023] (c) causing the jet stream of solution of aripiprazole in solvent and the jet stream of anti-solvent to strike each other and impinge on one another to create high turbulence at their point of impact, each jet stream having sufficient linear velocity to achieve high intensity micromixing of each stream prior to nucleation, to produce a slurry of crystals of aripiprazole monohydrate; and
[0024] (d) recovering crystals of aripiprazole monohydrate of desired small particle size and narrow particle size distribution.
[0025] Prior to step (d) ultasonic energy may be provided, by means of a sonication probe, as described in U.S. Pat. No. 6,302,958, the disclosure of which is incorporated herein by reference, the tip of which is positioned within a gap defined between the two jet streams, to cause the impinging jet streams to achieve high intensity micromixing of fluids prior to nucleation.
[0026] In addition, in accordance with the present invention, a preferred process is provided for preparing sterile bulk aripiprazole of desired average particle size of less than about 100 microns, but preferably greater than 25 microns, and narrow particle size distribution, which includes the steps of:
[0027] (a) providing a jet stream of a solution of aripiprazole in ethanol heated at a temperature within the range from about 70 to about 85° C., preferably from about 75 to about 80° C.;
[0028] (b) providing a jet stream of deionized water which is at a temperature within the range from about 2 to about 40° C., preferably from about 20 to about 35° C.;
[0029] (c) causing the jet streams of solution of aripiprazole and water, each at a flow rate (where jet nozzles of 0.02 inch internal diameter are employed) within the range from about 0.20 to about 0.30 kg/min, preferably from about 0.22 to about 0.28 kg/min, to impinge on one another to create high turbulence at their point of impact to achieve high intensity micromixing of each stream prior to nucleation, and form a slurry of crystals of aripiprazole monohydrate; and
[0030] (d) recovering crystals of aripiprazole monohydrate having an average particle size less than 100 microns, but preferably greater than 25 microns, preferably about 95% of the crystals having a particle size less than 100 microns.
[0031] Prior to step (d) ultasonic energy may be provided, by means of a sonication probe, as described above, the tip of which is positioned within a gap defined between the two jet streams, to cause the impinging jet streams to achieve high intensity micromixing of fluids prior to nucleation.
[0032] In carrying out the above process of the invention, the volumetric ratio of solution of aripiprazole in organic solvent to anti-solvent is within the range from about 0.5:1 to about 1.5:1, preferably from about 0.9:1 to about 1.1:1.
[0033] The above processes may also be employed to prepare crystals of aripiprazole monohydrate having an average particle size of less than 25 microns.
[0034] The processes of the invention as described above employs jet streams which impinge on each other to achieve high intensity micromixing of the streams to enable formation of a homogeneous composition prior to the start of nucleation in a continuous crystallization process. Nucleation and precipitation are initiated utilizing the effect of antisolvent addition on the solubility of the aripiprazole in the solvent therefore.
[0035] The sonication steps disclosed above are carried out as described in U.S. Pat. No. 6,302,958.
[0036] The aripiprazole produced by the process of the invention may be employed in forming sterile bulk aripiprazole having a desired particle size distribution, preferably 10% <10 microns, 50% <35 microns and 95% <100 microns, and mean particle size within the range from about 25 to about 100 microns.
[0037] The sterile bulk aripiprazole prepared by the process of the invention may be used in forming a sterile-freeze dried aripiprazole formulation which may be suspended in water to form an injectable aripiprazole formulation as described in U.S. provisional Application No. 10/419,647.
[0038] Each of the above embodiments of the process of the invention are referred to as the impinging jet crystallization process of the invention.
[0039] The process of the invention employs impinging jet crystallization technology, an example of which is disclosed in U.S. Pat. No. 5,314,506 to Midler et al.
[0040] It will also be appreciated that the sterile bulk aripiprazole of desired small particle size and narrow particle size distribution as described above may be prepared employing the process and apparatus described and claimed in each of the Chendou Wei applications entitled “Crystallization System Using Atomization” and “Crystallization System Using Homogenization” described above and incorporated herein by reference.
BRIEF DESCRIPTION OF THE FIGURES
[0041] The accompanying FIGURE is a schematic representation of an impinging jet crystallization process flow diagram used in carrying out the process of the invention, which includes a crystallizer vessel.
DETAILED DESCRIPTION OF THE INVENTION
[0042] The process of the invention is illustrated in the following reaction scheme:
[0000]
[0043] In carrying out the process of the invention, low pyrogen aripiprazole starting material is employed to ensure that the sterile aripiprazole of desired particle size will be produced. The low pyrogen aripiprazole starting material may be either the anhydrous form or the monohydrate form. Either material will yield the desired monohydrate form from the impinging jet crystallization process of the invention.
[0044] The process of the invention employs two jet nozzles to create two impinging jet streams to achieve high intensity micromixing of the streams prior to nucleation and formation of crystals of aripiprazole monohydrate. The two impinging jet streams should be substantially diametrically opposed to one another with the nozzles directed to face each other. The jet nozzles will be aligned and positioned so that the fluid streams will impact head-on and will impinge. When the jet nozzles are properly aligned and appropriate flow rates chosen, the two streams will form a plane when impinged.
[0045] Each of the process streams, namely the aripiprazole-organic solvent stream and the anti-solvent stream will be sterilized. To sterilize the two process streams, both streams are preferably polish filtered and then sterile filtered through an appropriate size filter, such as a 0.2 micron filter. The aripiprazole stream should be filtered at an elevated temperature, for example, about 80° C., to prevent precipitation.
[0046] The temperature and composition of each solution are chosen so that 1) no material will crystallize upstream of the impinging jets, and 2) sufficient supersaturation will be developed in the impinging jets to cause nucleation. Micromixing creates temperature and compositional uniformity throughout the mixture prior to the start of nucleation.
[0047] To obtain the smallest particle size of aripiprazole, the highest possible concentration of aripiprazole in the organic solvent should be employed. Thus, the starting solution of aripiprazole in organic solvent, preferably ethanol, will contain from about 0.01 to about 0.1 kg/L aripiprazole, preferably from about 0.04 to about 0.06 kg/L aripiprazole. In a most preferred embodiment, the aripiprazole will be present in an amount of about 0.05 kg/L.
[0048] The organic solvent will preferably be ethanol, most preferably from about 92 to about 97% ethanol, with the remainder being water.
[0049] Other organic solvents, such as methanol, ethyl acetate, acetone, acetonitrile, acetic acid or isopropyl alcohol or mixtures of two or more thereof, or mixtures with water may be employed.
[0050] The anti-solvent will preferably be deionized water.
[0051] The two streams, namely, the stream of the solution of aripiprazole in the organic solvent and the stream of anti-solvent, are characterized as jet streams in that they will be made to strike each other head on at high linear velocities with a minimum of 5 m/s. The flow rates will be determined by the diameter of the jet nozzles employed to deliver the streams and the rate at which the streams are pumped through the nozzles. In a preferred embodiment, the flow rate of each of the stream of aripiprazole/solvent and the stream of antisolvent will be essentially the same, but will of course be in opposite directions.
[0052] The flow rates will be chosen so that proper impinging is achieved. For example, where jet nozzles of 0.02 inch internal diameter are employed, flow rates will be within the range from about 0.20 to about 0.30 kg/min, preferably from about 0.22 kg/min to about 0.28 kg/min, more preferably from about 0.24 kg/min to about 0.26 kg/min, and optimally about 0.25 kg/min.
[0053] The temperature of each of the streams is important in determining ultimate size of the particles of aripiprazole produced. Thus, the aripiprazole-solvent (preferably ethanol) stream should be heated at a temperature within the range from about 70 to about 85° C., preferably from about 75 to about 80° C. The anti-solvent stream (preferably water) should be at a temperature substantially less than the temperature of the aripiprazole-solvent stream, and within the range from about 2 to about 40° C., preferably from about 20 to about 35° C., and optimally about 30° C.
[0054] The two streams strike each other head-on, from opposite directions, to cause rapid homogeneous mixing and supersaturation due to high turbulence and high intensity of mixing upon impact. The immediate achievement of supersaturation initiates rapid nucleation. In general, the average crystal size decreases with increasing supersaturation and decreasing temperature of the anti-solvent. The smallest particle size of aripiprazole is obtained employing the highest possible concentration of the aripiprazole solution and the lowest temperature of the anti-solvent. Sonication is utilized where even smaller particles are desired.
DESCRIPTION OF THE FIGURE
[0055] Referring to the accompanying FIGURE, an impinging jet crystallization process flow diagram and crystallizer vessel used in carrying out the process of the invention are shown which includes a jacketed impingement crystallization vessel 10 . There are two jacketed-vessels 12 , 14 that flank the impingement vessel 10 to the left and right which contain the aripiprazole-rich solution ( 12 ) and the anti-solvent ( 14 ), respectively. Both of these side vessels 12 , 14 are spaced apart from the impingement vessel 10 . Impinging jet nozzles 16 , 18 , each having a 0.02-inch diameter, are spaced 10 mm apart. The impingement vessel 10 may include agitator 11 and a sonicator (as employed in U.S. Pat. No. 6,302,958), if desired, not shown for drawing clarity. Outlet 31 of impingement vessel 10 is connected to receiving vessel 32 , via line 33 . Overflow line 35 links impingement vessel 10 and line 33 and aids in maintaining a constant volume in impingement vessel 10 .
[0056] The above description is of the sterile portion of the flow diagram. The non-sterile portion as shown includes a vessel 34 for holding a solution of aripiprazole in ethanol, preferably 95% ethanol, which is pumped via pump 36 through polish filter 38 and sterile filter 40 into vessel 12 and processed as described above.
[0057] The jet nozzles 16 , 18 should be placed so that the fluid streams they emit will impinge, inside the stirred impingement vessel 10 or inside a separate jet chamber (not shown) which is linked directly to the vessel 10 . The fluid jets must impinge to create an immediate high turbulence impact. The two jet nozzles are preferably arranged so that they are substantially diametrically opposed to each other with their outlet tips directed to face each other; i.e., the two jet nozzles are at or close to a 180 degree angle to each other from an overhead view. Preferably, each jet outlet nozzle can have a slight downward angle from the horizontal, for example, about 10 degrees, to help the flowing material move down and out of the chamber.
[0058] Likewise, two jet nozzles placed directly inside the stirred impingement vessel 10 are preferably arranged so that they are substantially diametrically opposed to each other with their outlet tips directed to face each other. When the jet nozzles are so placed, each nozzle can have a slight upward or downward angle from the horizontal of from 0 degrees up to about 15 degrees, but preferably the two nozzles have just enough downward angle from the horizontal (ca. 13 degrees) to ensure that the fluid stream of one will not enter the outlet hole of the opposite nozzle.
[0059] Jet nozzle 16 is used to transport aripiprazole solution into the vessel 10 (or separate jet chamber) and the other jet 18 is used to similarly transport water. The distance between the nozzle tips inside the jet chamber or vessel 10 should be such that the hydro-dynamic form of each fluid jet stream remains essentially intact up to the point of impingement. Therefore, the maximum distance between the nozzle tips will vary depending on the linear velocity of the fluids inside the jet nozzles. To obtain good results for generally non-viscous fluids, linear velocity in the jet nozzles should be at least about 5 meters/sec., more preferably above 10 meters/sec., and most preferably between about 20 to 25 meters/sec., although the upper limit of linear velocity is only limited by the practical difficulties involved in achieving it. Linear velocity and flow rate can both be controlled by various known methods, such as altering the diameter of the entry tube and/or that of the nozzle outlet tip, and/or varying the strength of the external force that moves the fluid into and through the nozzle. Each jet apparatus can be manipulated independently to attain a desired final fluid composition ratio. When the desired flow ratio of one jet to the other differs from unity, preferably the difference is compensated for by appropriate sizing of the entry tubes. For example, if a 4:1 volumetric ratio of feed solution to anti-solvent is desired, the entry tube delivering feed solution should be twice the diameter of the entry tube delivering anti-solvent. When the jet streams impinge inside a jet chamber, residence time for the fluid inside the jet chamber is typically very short, i.e., less than ten seconds.
[0060] Stirring in the vessel is provided by standard agitators 11 , preferably Rushton 10 turbines, Intermig impellers, or other agitators suitable for stirring a slurry suspension. Any impeller providing good circulation inside the vessel may be used. However, when the jet streams are arranged to impinge directly inside the stirred vessel, an agitator that does not interfere with the space occupied by the impinging jet streams inside the vessel is preferred, especially, e.g., a Rushton turbine. Impinging jet streams inside the vessel are most preferably placed in the effluent stream of the agitator, and the height of the liquid in the stirred vessel 10 when operated in continuous mode (i.e., flow in equals flow out, constant volume maintained), is most preferably between about two to four times the height of the impeller.
[0061] The crystallization is preferably run in a continuous process and the appropriate residence time for the completion of crystal digestion is attained by adjusting the volume capacity of the stirred vessel, but the mixture can be held up in the vessel for any desired length of age time if batchwise processing is desired.
[0062] Manual seeding can be done at any point in the system, e.g., in the stirred vessel 10 , the transfer line or the jet chamber itself. In some situations, the continuous jet process may be “self-seeding”, i.e., the first crystals to form inside the jet chamber (if used), the transfer line (if used) or the stirred vessel 10 serve as seed for the material that flows through thereafter.
[0063] The micromixed material must be highly supersaturated to attain the beneficial results of the jet crystallization process. Aside from thermoregulated initiation of nucleation, temperature variation also affects product results when anti-solvent is used to initiate nucleation because of its effect on supersaturation. Generally, good results can be achieved using a volumetric ratio of aripiprazole to anti-solvent that provides a high degree of supersaturation in the jet chamber in a temperature range of about 24° C. to 70° C., although the temperature upper limit is limited only by the chosen solvent's boiling point.
[0064] An example of the impingement vessel which may be employed is disclosed in U.S. Pat. No. 5,314,506 to Midler et al. and in U.S. Pat. No. 6,302,958 to Lindrud et al. which are incorporated herein by reference.
[0065] To prepare a 100-gram batch of aripiprazole monohydrate, a 100 grams of aripiprazole anhydrous N1 is charged into a 4-L vessel 12 and dissolved in 2 L of 95% ethanol at 75 to 80° C. The clear solution is then transferred to the product-rich 2-L jacketed vessel 10 and maintained at 75 to 80° C. In the anti-solvent vessel 14 , 2 L of deionized (DI) water is then charged and heated to 28 to 32° C. When both liquids are at the desired temperatures, the two streams are pumped simultaneously via pumps 20 and 22 through mass flow meters 24 , 26 , respectively, and sterile filters 28 , 30 , respectively, through the 0.02-inch internal diameter nozzles 16 , 18 and impinge at a rate of 0.22 to 0.28 kg/min to produce the monohydrate crystals. The crystals are continuously transferred to receiving vessel 32 to maintain a constant volume in the impingement vessel 10 . It takes approximately 5 to 7 minutes to impinge a 100-gram batch. The slurry is cooled to 20 to 25° C., filtered, and washed with 200 mL of deionized water. The cake is then dried at 35° C. under vacuum to obtain approximately 100 grams of aripiprazole monohydrate, H0, with a Karl Fisher % (KF %) of ca. 4% w/w.
EXAMPLES
[0066] The following working Examples represent preferred embodiments of the present invention.
Example 1
[0067] Sterile bulk active pharmaceutical ingredient (API) aripiprazole was prepared using impinging crystallization with sonication employing an apparatus set up as shown in the attached FIGURE.
[0068] The following procedure was employed to form a sterile bulk aripiprazole.
[0069] 1. Charge 100 g of aripiprazole in a 4 L flask 34 .
[0070] 2. Add 2 L of 95% ethanol.
[0071] 3. Heat the suspension to 80° C. until it becomes a clear solution.
[0072] 4. Transfer the hot aripiprazole solution to a 2 L jacketed vessel 12 and maintain at 75-80° C.
[0073] 5. Charge 2 L of deionized (DI) water to a 2 L jacketed vessel 14 .
[0074] 6. Cool the DI water to 2° C.
[0075] 7. Add 100 mL of 95% ethanol and 100 mL of DI water to the impinging vessel 10 and cool to 2° C.
[0076] 8. Initiate sonication (Sonication is provided by a 0.5 inch probe with 120 W power output employed as described in U.S. Pat. No. 6,302,958).
[0077] 9. Pump the aripiprazole solution through a 0.02 inch diameter nozzle 16 at 0.25 kg/min and impinge it with the 2° C. water pumped at 0.25 kg/min through a 0.02 inch diameter nozzle 18 .
[0078] 10. Sonicate the newly formed crystal slurry in the impinge vessel 10 while continuously transferring the crystals to a receiving vessel 32 to maintain a constant volume in the impingement vessel 10 .
[0079] 11. Cool the slurry to 20 to 25° C. at the end of impingement.
[0080] 12. Filter the slurry.
[0081] 13. Wash the cake with 200 mL of DI water.
[0082] 14. Dry the wet cake at 35° C. under vacuum to obtain 97.9 g of aripiprazole with a KF of 4.0% w/w, with reduced particle size (95% <100 microns).
Example 2
[0083] Sterile bulk API aripiprazole was prepared using impinging jet crystallization and an apparatus set up as shown in the accompanying FIGURE.
[0084] The following procedure was employed to form a sterile bulk aripiprazole:
[0085] 1. Suspend 100 g of aripiprazole in 2000 mL of 95% ethanol. Heat the suspension to 80° C. until it becomes a clear solution.
[0086] 2. Polish filter the aripiprazole solution into a holding vessel 12 and maintain at 80° C.
[0087] 3. Polish filter 2000 mL water to another holding vessel 14 and heat to 80° C.
[0088] 4. Pump the aripiprazole solution through a 0.02 inch diameter nozzle 16 at 0.25 kg/min and impinge it with the 30° C. water pumped at 0.25 kg/min through a 0.02 inch diameter nozzle 18 to form a crystal slurry which is collected in an impingement vessel 10 .
[0089] 5. Agitate the newly formed crystal slurry in the impingement vessel 10 while continuously transferring it to a receiver 32 to maintain a constant volume in the impingement vessel 10 .
[0090] 6. At the end of impingement, cool the slurry in the receiver 32 to room temperature.
[0091] 7. Filter the slurry.
[0092] 8. Dry the wet cake at 35° C. under vacuum to yielding 100 g (96% recovery) of aripiprazole with reduced particle size (95% <100 microns).
Example 3
[0093] An aripiprazole injectable aqueous suspension (200 mg aripiprazole/2 mL, 200 mg/vial) was prepared as follows.
[0094] The following ingredients were added to a 3 L glass jacketed vessel maintained at 15° C. (±5° C.) to form a sterile primary suspension:
[0000]
Aripiprazole (prepared by impinging jet
100 g
crystallization as described in Example 2):
Carboxymethylcellulose, Sodium Salt 7L2P
9.0 g
Mannitol
45 g
Sodium Phosphate, Monobasic
0.8 g
Sodium Hydroxide Solution, 1N
q.s. to adjust pH to 7.0
Water, USP
q.s. to 1000 g
[0095] The sterile suspension was mixed at 500-1000 rpm for about 0.5 hour and then at 300-500 rpm for an additional 1 hour under 20″ Hg (±5″Hg) vacuum.
[0096] 2.5 mL of the above suspension were aseptically filled into sterilized vials which were then aseptically partially stoppered with sterilized stoppers. The vials were aseptically transferred to a freeze dryer and lyophilized according to the following cycle:
[0097] (a) thermal treatment: freeze product at −40° C. over 0.1-1 h and keep at −40° C. for at least 6 h,
[0098] (b) cool the condenser to −50° C. or below,
[0099] (c) primary drying: lower chamber pressure to approximately 100 microns Hg and increase product temperature to −5° C. over approximately 2 h; continue primary drying at −5° C. and 100 microns Hg for at least 48 h,
[0100] (d) stopper the vials under atmospheric pressure or partial vacuum using sterile nitrogen or air and remove from the freeze dryer,
[0101] (e) seal the vials with the appropriate seals and label.
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A process is provided for making sterile aripiprazole having an average particle size less than 100 microns but preferably greater than 25 microns employing an impinging jet crystallization procedure. The resulting bulk aripiprazole of desired particle size may be used to form a sterile freeze-dried aripiprazole formulation, which upon constitution with water and intramuscular injection releases aripiprazole over a period of at least about one week and up to about eight weeks.
| 1 |
TECHNICAL FIELD OF THE INVENTION
[0001] The present invention relates to a building block comprising a complementing element and precursor for a functional entity. The building block is designed to transfer the functional entity with an adjustable efficiency to a recipient reactive group upon recognition between the complementing element and an encoding element associated with the reactive group. The invention also relates to a linkage between the functional entity and the complementing element as well as a method for transferring a functional entity to recipient reactive group.
BACKGROUND
[0002] The transfer of a chemical entity from one mono-, di- or oligonucleotide to another has been considered in the prior art. Thus, N. M. Chung et al. (Biochim. Biophys. Acta, 1971, 228,536-543) used a poly(U) template to catalyse the transfer of an acetyl group from 3′-O-acetyladenosine to the 5′-OH of adenosine. The reverse transfer, i.e. the transfer of the acetyl group from a 5′-O-acetyladenosine to a 3′-OH group of another adenosine, was also demonstrated.
[0003] Waider et al. Proc. Natl. Acad. Sci. USA, 1979, 76, 51-55 suggest a synthetic procedure for peptide synthesis. The synthesis involves the transfer of nascent immobilized polypeptide attached to an oligonucleotide strand to a precursor amino acid attached to an oligonucleotide. The transfer comprises the chemical attack of the amino group of the amino acid precursor on the substitution labile peptidyl ester, which in turn results in an acyl transfer. It is suggested to attach the amino acid precursor to the 5′ end of an oligonucleotide with a thiol ester linkage.
[0004] The transfer of a peptide from one oligonucleotide to another using a template is disclosed in Bruick R K et al. Chemistry & Biology, 1996, 3:49-56. The carboxy terminal of the peptide is initially converted to a thioester group and subsequently transformed to an activated thioester upon incubation with Ellman's reagent. The activated thioester is reacted with a first oligo, which is 5′-thiol-terminated, resulting in the formation of a thio-ester linked intermediate. The first oligonucleotide and a second oligonucleotide having a 3′ amino group is aligned on a template such that the thioester group and the amino group are positioned in close proximity and a reaction is effected resulting in a coupling of the peptide to the second oligonucleotide through an amide bond.
[0005] The prior art building blocks and methods for transfer have a relatively poor transfer efficiency. Therefore, in an aspect of the present invention an oligonucleotide conjugated to a transferable chemical moiety via a linker is provided, which has an increased ability to transfer a functional entity.
SUMMARY OF THE INVENTION
[0006] The present invention relates to a building block of the general formula
capable of transferring a functional entity (FE) to a recipient reactive group, wherein
[0007] the lower horizontal line is a Complementing Element identifying the functional entity and the vertical line between the complementing element and the S atom is a Spacer.
[0008] Preferably the spacer is a valence bond, C 1 -C 6 alkylene-A-, C 1 -C 6 alkenylene-A-, C 2 -C 6 alkynylene-A-, or
said spacer optionally being connected through A to a moiety selected from
—(CH 2 ) n —S—S—(CH 2 ) m —B—
where A is a valence bond, —C(O)NR 1 —, —NR 1 —, —O—, —S—, or —C(O)—O—; B is a valence bond, —O—, —S—, —NR 1 — or —C(O)NR 1 — and connects to the S atom of the carrier; R 1 is selected independently from H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 6 alkylene-aryl, or aryl substituted with 0-5 halogen atoms selected from —F, —Cl, —Br and —I; and n and m independently are integers ranging from 1 to 10.
[0009] In one aspect of the invention the Spacer is C 1 -C 6 alkylene-A-, C 1 -C 6 alkenylene-A-, C 2 -C 6 alkynylene-A-, or
said spacer optionally being connected through A to a moiety selected from
where A is —C(O)NR 1 —, or —S—; B is —S—, —NR 1 — or —C(O)NR 1 — and connects to S—C-connecting group; R 1 is selected independently from H, C 1 -C 6 alkyl, C 1 -C 6 alkylene-aryl, or aryl; and n and m independently are integers ranging from 1 to 6.
[0010] Preferably the Spacer is -A-, a group C 1 -C 6 alkylene-A-, C 2 -C 6 alkenylene-A-, or C 2 -C 6 alkynylene-A- optionally substituted with 1 to 3 hydroxy groups, or
said spacer being connected through A to a linker selected from
where A is a valence bond, —NR 2 —, —C(O)NR 2 —, —NR 2 —C(O)—, —O—, —S—, —C(O)—O— or OP(═O)(O − )—O—; B is a valence bond, —O—, —S—, —NR 2 —, —C(O)— or —C(O)NR 2 — and connects to S-C-connecting group; R 2 is selected independently from H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 6 alkylene-aryl,
G is H or C 1 -C 6 alkyl; and n and m independently are integers ranging from 1 to 10.
[0011] The spacer may connect to the complementing element in any convenient way. When the complementing element is a nucleic acid, the spacer may connect to the backbone or the nucleobase. In one aspect of the invention, the spacer is C 2 -C 6 alkenylene-A,
said spacer being connected through A to a moiety selected from
where A is a valence bond, —C(O)NR 2 —, —NR 2 —C(O)—, —S—, —C(O)—O— or OP(═O)(O − )—O—; B is a valence bond, —S—, —NR 2 —, or —C(O)— and connects to S-C-connecting group; n and m independently are integers ranging from 1 to 10 and R 2 is selected independently from H,
wherein G is H or C 1 -C 6 alkyl; and the spacer is connected to the complementing element through a nucleobase.
[0012] Suitably, the spacer is attached to the 5 position of a pyrimidine type nucleobase or 7 position of a purine or 7deaza-purine type nucleobase. However, other position of attachment may be appropriate.
[0013] In another aspect of the invention the spacer is -A-,
said spacer being connected through A to a moiety selected from
where A is a valence bond, —NR 2 —C(O)—, —O—, or —S—; B is a valence bond, —S—, —NR 2 —, or —C(O)— and connects to S-C-connecting group;
[0014] n and m independently are integers ranging from 1 to 10 and
[0015] R 2 is selected independently from H,
wherein G is H or C 1 -C 6 alkyl; and the spacer is connected to the complementing element via a phosphorus group.
[0016] The phosphorus group is suitable a phosphate or thiophosphate group attached to a 3′ or 5′ end of a complementing element.
[0017] The building block according to the present invention can transfer a variety of chemical compounds to a recipient reactive group. In one aspect of the invention the functional entity is of the format,
where X=—C—, —S—, —P—, —S(O)—, —P(O)—, and V=O, S, NH, N-C 1 -C 6 alkyl. R may be chosen from any chemical group capable of forming a chemical bond to the X atom. In a preferred aspect of the invention FE is
where
[0018] X=—C—, —S—, —P—, —S(O)—, or —P(O)—, V=O, S, NH, or N-C 1 -C 6 alkyl, and
[0019] R is H or selected among the group consisting of a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 4 -C 8 alkadienyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl, and heteroaryl, said group being substituted with 0-3 R 4 , 0-3 R 5 and 0-3 R 9 or C 1 -C 3 alkylene-NR 4 2 , C 1 -C 3 alkylene-NR 4 C(O)R 8 , C 1 -C 3 alkylene-NR 4 C(O)OR 8 , C 1 -C 2 alkylene-O-NR 4 2 , C 1 -C 2 alkylene-O-NR 4 C(O)R 18 , C 1 -C 2 l alkylene-O-NR 4 C(O)OR 8 substituted with 0-3 R 9 .
[0020] where R 4 is H or selected independently among the group consisting of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl, heteroaryl, said group being substituted with 0-3 R 9 and
[0021] R 5 is selected independently from —N 3 , —CNO, —C(NOH)NH 2 , —NHOH, —NHNHR 6 , —C(O)R 6 , —SnR 6 3 , —B(OR 6 ) 2 , —P(O)(OR 6 ) 2 or the group consisting of C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 4 -C 8 alkadienyl said group being substituted with 0-2 R 7 ,
[0022] where R 6 is selected independently from H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl or C 1 -C 6 alkylene-aryl substituted with 0-5 halogen atoms selected from —F, —Cl, —Br, and —I; and R 7 is independently selected from —NO 2 , —COOR 6 , —COR 6 , —CN, —OSiR 6 3 , —OR 6 and —NR 6 2 .
[0023] R 8 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, aryl or C 1 -C 6 alkylene-aryl substituted with 0-3 substituents independently selected from —F, —Cl, —NO 2 , —R 3 , —OR 3 , —SiR 3 3
[0024] R 9 is ═O, —F, —Cl, —Br, —I, —CN, —NO 2 , —OR 6 , —NR 6 2 , —NR 6 —C(O)R 6 , —NR 6 —C(O)OR 8 , —SR 6 , —S(O)R 8 , —S(O) 2 R 6 , —COOR 6 , —C(O)NR 6 2 and —S(O) 2 NR 6 2 .
[0025] In a certain aspect of the invention, R is H or selected among the group consisting of a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 C 6 alkynyl, C 4 -C 6 alkadienyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl, and heteroaryl, said group being substituted with 0-3 R 5 and 0-3 R 9 , or selected among the group consisting of C 1 -C 3 alkylene-NR 4 2 , C 1 -C 3 alkylene-NR 4 C(O)R 8 , C 1 -C 3 alkylene-NR 4 C(O)OR 8 , C 1 -C 2 alkylene-O-NR 4 2 , C 1 -C 2 alkylene-ONR 4 C(O)R 8 , and C 1 -C 2 alkylene-O-NR 4 C(O)OR 8 substituted with 0-3 R 9 .
[0026] Suitably, R is H or selected among the group consisting of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 4 -C 8 alkadienyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl, and heteroaryl, said group being substituted with 0-3 R 5 and 0-3 R 9 .
[0027] In some aspects of the invention it is preferred that R is selected among the group consisting of C 1 -C 3 alkylene-NR 4 2 , C 1 -C 3 alkylene-NR 4 C(O)R 8 , C 1 -C 3 alkylene-NR 4 C(O)OR 8 , C 1 -C 2 alkylene-O—NR 4 2 , C 1 -C 2 alkylene-O—NR 4 C(O)R 8 , and C 1 -C 2 alkylene-O—NR 4 C(O)OR 8 substituted with 0-3 R 9 .
[0028] In the present description and claims, the direction of connections between the various components of a building block should be read left to right. For example a spacer is connected to a complementing element through the atom on the left and to the sulphur atom (or alternatively the group A) through the atom on the right hand side.
[0029] The term “C 3 -C 7 cycloheteroalkyl” as used herein refers to a radical of totally saturated heterocycle like a cyclic hydrocarbon containing one or more heteroatoms selected from nitrogen, oxygen, phosphor, boron and sulphur independently in the cycle such as pyrrolidine (1-pyrrolidine; 2-pyrrolidine; 3-pyrrolidine; 4-pyrrolidine; 5-pyrrolidine); pyrazolidine (1-pyrazolidine; 2-pyrazolidine; 3-pyrazolidine; 4-pyrazolidine; 5-pyrazolidine); imidazolidine (1- imidazolidine; 2-imida-zolidine; 3-imidazolidine; 4-imidazolidine; 5-imidazolidine); thiazolidine (2-thiazolidine; 3-thiazolidine; 4-thiazolidine; 5-thiazolidine); piperidine (1-piperidine; 2-piperidine; 3-piperidine; 4-piperidine; 5-piperidine; 6-piperidine); piperazine (1-piperazine; 2-piperazine; 3-piperazine; 4-piperazine; 5-piperazine; 6-piperazine); morpholine (2-morpholine; 3-morpholine; 4-morpholine; 5-morpholine; 6-morpholine); thiomorpholine (2-thiomorpholine; 3-thiomorpholine; 4-thiomorpholine; 5-thiomorpholine; 6-thiomorpholine); 1,2-oxathiolane (3-(1,2-oxathiolane); 4-(1,2-oxathiolane); 5-(1,2-oxathiolane); 1,3-dioxolane (2-(1,3-dioxolane); 4-(1,3-dioxolane); 5-(1,3-dioxolane); tetrahydropyrane; (2-tetrahydropyrane; 3-tetrahydropyrane; 4-tetrahydropyrane; 5-tetrahydropyrane; 6-tetrahydropyrane); hexahydropyridazine (1-(hexahydropyridazine); 2-(hexahydropyridazine); 3-(hexahydropyridazine); 4-(hexahydropyridazine); 5-(hexahydropyridazine); 6-(hexahydropyridazine)), [1,3,2]dioxaborolane, [1,3,6,2]dioxazaborocane
[0030] The term “aryl” as used herein includes carbocyclic aromatic ring systems of 5-7 carbon atoms. Aryl is also intended to include the partially hydrogenated derivatives of the carbocyclic systems as well as up to four fused aromatic- or partially hydrogenated rings, each ring comprising 5-7 carbon atoms.
[0031] The term “heteroaryl” as used herein includes heterocyclic unsaturated ring systems containing, in addition to 2-18 carbon atoms, one or more heteroatoms selected from nitrogen, oxygen and sulphur such as furyl, thienyl, pyrrolyl, heteroaryl is also intended to include the partially hydrogenated derivatives of the heterocyclic systems enumerated below.
[0032] The terms “aryl” and “heteroaryl” as used herein refers to an aryl which can be optionally substituted or a heteroaryl which can be optionally substituted and includes phenyl, biphenyl, indenyl, naphthyl (1-naphthyl, 2-naphthyl), N-hydroxytetrazolyl, N-hydroxytriazolyl, N-hydroxyimidazolyl, anthracenyl (1-anthracenyl, 2-anthracenyl, 3-anthracenyl), thiophenyl (2-thienyl, 3-thienyl), furyl (2-furyl, 3-furyl), indolyl, oxadiazolyl, isoxazolyl, quinazolinyl, fluorenyl, xanthenyl, isoindanyl, benzhydryl, acridinyl, thiazolyl, pyrrolyl (2-pyrrolyl), pyrazolyl (3-pyrazolyl), imidazolyl (1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl (1,2,3-triazol-1-yl, 1,2,3-triazol-2-yl 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), benzo[b]furanyl (2-benzo[b]furanyl, 3-benzo[b]furanyl, 4-benzo[b]furanyl, 5-benzo[b]furanyl, 6-benzo[b]furanyl, 7-benzo[b]furanyl), 2,3-dihydro-benzo[b]furanyl (2-(2,3-dihydro-benzo[b]furanyl), 3-(2,3-dihydro-benzo[b]furanyl), 4-(2,3-dihydro-benzo[b]furanyl), 5-(2,3-dihydro-benzo[b]furanyl), 6-(2,3dihydro-benzo[b]furanyl), 7-(2,3-dihydro-benzo[b]furanyl), benzo[b]thiophenyl (2-benzo[b]thiophenyl, 3-benzo[b]thiophenyl, 4-benzo[b]thiophenyl, 5-benzo[b]thiophenyl, 6-benzo[b]thiophenyl, 7-benzo[b]thiophenyl), 2,3-dihydro-benzo[b]thiophenyl (2-(2,3-dihydro-benzo[b]thiophenyl), 3-(2,3-dihydro-benzo[b]thiophenyl), 4-(2,3-dihydro-benzo[b]thiophenyl), 5-(2,3-dihydro-benzo[b]thiophenyl), 6-(2,3-dihydro-benzo[b]thiophenyl), 7-(2,3-dihydro-benzo[b]thiophenyl), indolyl (1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), indazole (1-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl, 7-indazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 8-benzimidazolyl), benzoxazolyl (1-benzoxazolyl, 2-benzoxazolyl), benzothiazolyl (1-benzothiazolyl, 2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), carbazolyl (1-carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl), 5H-dibenz[b,f]azepine (5H-dibenz[b,f]azepin-1-yl, 5H-dibenz[b,f]azepine-2-yl, 5H-dibenz[b,f]azepine-3-yl, 5H-dibenz[b,f]azepine-5-yl, 5H-dibenz[b,f]azepine-5-yl), 10,11-dihydro-5H-dibenz[b,f]azepine (10,11-dihydro-5H-dibenz[b,f]azepine-1-yl, 10,11-dihydro-5H-dibenz[b,f]azepine-2-yl, 10,11-dihydro-5H-dibenz[b,f]azepine-3-yl, 10,11-dihydro-5H-dibenz[b,f]azepine4-yl, 10,11-dihydro-5H-dibenz[b,f]azepine-5-yl).
[0033] The Functional Entity carries elements used to interact with host molecules and optionally reactive elements allowing further elaboration of an encoded molecule of a library. Interaction with host molecules like enzymes, receptors and polymers is typically mediated through van der waal's interactions, polar- and ionic interactions and pi-stacking effects. Substituents mediating said effects may be masked by methods known to an individual skilled in the art (Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; 3rd ed.; John Wiley & Sons: New York, 1999.) to avoid undesired interactions or reactions during the preparation of the individual building blocks and during library synthesis. Analogously, reactive elements may be masked by suitably selected protection groups. It is appreciated by one skilled in the art that by suitable protection, a functional entity may carry a wide range of substituents.
[0034] The Functional Entity may be a masked Functional Entity that is incorporated into an encoded molecule. After incorporation, reactive elements of the Functional Entity may be revealed by unmasking allowing further synthetic operations. Finally, elements mediating recognition of host molecules may be un-masked.
[0035] The function of the carrier
is to provide for the transferability of the functional entity, playing the role of a leaving group.
[0036] The spacer serves to distance the functional entity to be transferred from the bulky complementing element. Thus, the identity of the spacer is not crucial for the function of the building block. It may be desired to have a spacer which can be cleaved by light. In this occasion, the spacer is provided with e.g. the group
[0037] In the event an increased hydophilicity is desired the spacer may be provided with a polyethylene glycol part of the general formula:
[0038] The spacer in conjunction with the carrier makes up a cleavable linker, which links the complementing element to the functional entity.
[0039] In a preferred embodiment, the complementing element serves the function of transferring genetic information e.g. by recognising a coding element. The recognition implies that the two parts are capable of interacting in order to assemble a complementing element—coding element complex. In the biotechnological field a variety of interacting molecular parts are known which can be used according to the invention. Examples include, but are not restricted to protein-protein interactions, protein-polysaccharide interactions, RNA-protein interactions, DNA-DNA interactions, DNA-RNA interactions, RNA-RNA interactions, biotin-streptavidin interactions, enzyme-ligand interactions, antibody-ligand interaction, protein-ligand interaction, ect.
[0040] The interaction between the complementing element and coding element may result in a strong or a week bonding. If a covalent bond is formed between the parties of the affinity pair the binding between the parts can be regarded as strong, whereas the establishment of hydrogen bondings, interactions between hydrophobic domains, and metal chelation in general results in weaker bonding. In general relatively weak bonding is preferred. In a preferred aspect of the invention, the complementing element is capable of reversible interacting with the coding element so as to provide for an attachment or detachment of the parts in accordance with the changing conditions of the media.
[0041] In a preferred aspect of the invention, the interaction is based on nucleotides, i.e. the complementing element is a nucleic acid. Preferably, the complementing element is a sequence of nucleotides and the coding element is a sequence of nucleotides capable of hybridising to the complementing element. The sequence of nucleotides carries a series of nucleobases on a backbone. The nucleobases may be any chemical entity able to be specifically recognized by a complementing entity. The nucleobases are usually selected from the natural nucleobases (adenine, guanine, uracil, thymine, and cytosine) but also the other nucleobases obeying the Watson-Crick hydrogen-bonding rules may be used, such as the synthetic nucleobases disclosed in U.S. Pat. No. 6,037,120. Examples of natural and non-natural nucleobases able to perform a specific pairing are shown in FIG. 2 . The backbone of the sequence of nucleotides may be any backbone able to aggregate the nucleobases is a sequence. Examples of backbones are shown in FIG. 4 . In some aspects of the invention the addition of non-specific nucleobases to the complementing element is advantageous, FIG. 3 .
[0042] The coding element can be an oligonucleotide having nucleobases which complements and is specifically recognised by the complementing element, i.e. in the event the complementing element contains cytosine, the coding element part contains guanine and visa versa, and in the event the complementing element contains thymine or uracil the coding element contains adenine.
[0043] The complementing element may be a single nucleobase. In the generation of a library, this will allow for the incorporation of four different functional entities into the template-directed molecule. However, to obtain a higher diversity a complementing element preferably comprises at least two and more preferred at least three nucleotides. Theoretically, this will provide for 4 2 and 4 3 , respectively, different functional entities uniquely identified by the complementing element. The complementing element will usually not comprise more than 100 nucleotides. It is preferred to have complementing elements with a sequence of 3 to 30 nucleotides.
[0044] The building blocks of the present invention can be used in a method for transferring a functional entity to a recipient reactive group, said method comprising the steps of
providing one or more building blocks as described above and contacting the one or more building blocks with a corresponding coding element associated with a recipient reactive group under conditions which allow for a recognition between the one or more complementing elements and the coding elements, said contacting being performed prior to, simultaneously with, or subsequent to a transfer of the functional entity to the recipient reactive group.
[0047] The coding element may comprise one, two, three or more codons, i.e. sequences that may be specifically recognised by a complementing element. Each of the codons may be separated by a suitable spacer group. Preferably, all or at least a majority of the codons of the template are arranged in sequence and each of the codons are separated from a neighbouring codon by a spacer group. Generally, it is preferred to have more than two codons on the template to allow for the synthesis of more complex encoded molecules. In a preferred aspect of the invention the number of codons of the encoding element is 2 to 100. Still more preferred are coding elements comprising 3 to 10 codons. In another aspect, a codon comprises 1 to 50 nucleotides and the complementing element comprises a sequence of nucleotides complementary to one or more of the encoding sequences.
[0048] The recipient reactive group may be associated with the encoding element in any appropriate way. Thus, the reactive group may be associated covalently or non-covalently to the coding element. In one embodiment the recipient reactive group is linked covalently to the encoding element through a suitable linker which may be separately cleavable to release the reaction product. In another embodiment, the reactive group is coupled to a complementing element, which is capable of recognising a sequence of nucleotides on the encoding element, whereby the recipient reactive group becomes attached to the encoding element by hybridisation. Also, the recipient reactive group may be part of a chemical scaffold, i.e. a chemical entity having one or more reactive groups available for receiving a functional entity from a building block.
[0049] The recipient reactive group may be any group able to cleave the bond between the carrier and the functional entity to release the functional entity. Usually, the reactive group is nucleophilic, such as a hydroxyl, a thiol, an amine etc. A preferred recipient reactive group is an amine group. The nucleophile usually attacks the atom of the functional entity connected to the oxygen attached to the nitrogen ring member of the carrier. When the functional entity is attached to said oxygen through a group X═V, the nucleophile attacks the X atom, thereby causing the carrier group to be a leaving group of the reaction, transferring the X(═V)-Functional entity precursor to the recipient. The chemical structure formed has, in the event the nucleophilic group is an amine attached to a scaffold, the general formula:
Scaffold-NH—X(═V)—R
[0050] In which
[0051] X=—C—, —S—, —P—, —S(O)—, —P(O)—, and
[0052] V=O, S, NH, N-C 1 -C 6 alkyl, and R is as previously defined.
[0053] In a preferred aspect X is C and V is O.
[0054] The conditions which allow for transfer to occur are dependent upon the receiving reactive group. Below various examples of the conditions for a transfer to occur are depicted together with the reaction products formed.
[0055] The present building blocks may be prepared in accordance with a variety of chemical synthesis schemes. Generally, a complementing element containing a thiol group is provided. In the event, the complementing element is a oligonucleotide, the thiol may be provided during the synthesis of the oligonucleotide by incorporating a suitable nucleotide derivative. When a oligonucleotide comprising a thiol group is desired, a variety of commercial nucleotide derivatives are available, e.g. the C6 S—S thiol modifier (obtainable from Glen Research cat. # 10-1936-90), which may be incorporated using the standard protocol of the phosphoramedite synthesis.
[0056] According to a first synthesis scheme the building block can be prepared using the step
[0057] The thiol oligonucleotide is reacted with the N-hydroxymaleimide-functional entity derivative via a Michael addition, whereby the SH group is added to the double bond of the maleimide.
[0058] According to a second synthesis scheme, the building blocks can be prepared in two step:
[0059] Error! Reference Source Not Found.
[0060] The thiol oligonucleotide is reacted with N-hydroxymaleimide via a Michael addition, whereby the SH group is added to the double bond of the maleimide forming an intermediate oligonucleotide derivative which is reacted further with a functional entity connected to a leaving group (Lg). Preferred leaving groups are
[0061] According to a preferred aspect of the invention the building blocks are used for the formation of a library of compounds. The complementing element of the building block is used to identify the functional entity. Due to the enhanced proximity between reactive groups when the complementing entity and the encoding element are contacted, the functional entity together with the identity programmed in the complementing element is transferred to the encoding element associated with recipient reactive group. Thus, it is preferred that the sequence of the complementing element is unique in the sense that the same sequence is not used for another functional entity. The unique identification of the functional entity enable the possibility of decoding the encoding element in order to determine the synthetic history of the molecule formed. In the event two or more functional entities have been transferred to a scaffold, not only the identity of the transferred functional entities can be determined. Also the sequence of reaction and the type of reaction involved can be determined by decoding the encoding element. Thus, according to a preferred embodiment of the invention, each different member of a library comprises a complementing element having a unique sequence of nucleotides, which identifies the functional entity.
BRIEF DESCRIPTION OF THE DRAWINGS
[0062] FIG. 1 shows to setups for functional entity transfer.
[0063] FIG. 2 shows examples of specific base pairing
[0064] FIG. 3 shows examples of non-specific base-pairing
[0065] FIG. 4 shows examples of backbones.
[0066] FIG. 5 discloses the results of example 7.
[0067] FIG. 6 discloses the results of example 8.
DETAILED DESCRIPTION OF THE INVENTION
[0068] A building block of the present invention is characterized by its ability to transfer its functional entity to a receiving chemical entity. This is done by forming a new covalent bond between the receiving chemical entity and cleaving the bond between the carrier moiety and the functional entity of the building block.
[0069] Two setups for generalized functional entity transfer from a building block are depicted in FIG. 1 . In the first example, one complementing element of a building block recognizes a template carrying another functional entity, hence bringing the functional entities in close proximity. This results in a reaction between functional entity 1 and 2 forming a covalent bond between these concurrent with the cleavage of the bond between functional entity 2 and its linker. In the second example, a template brings together two building blocks resulting in functional entity transfer from one building block to the other.
[0070] In a library synthesis, several building blocks are mixed in a reaction vessel and the added templates ensure that the building blocks—consequently the functional entities—are combined in the desired manner. As several building blocks are employed at the same time, the use of in situ generated building blocks is disfavoured for practical reasons.
[0071] Building blocks for library synthesis should posses the necessary reactivity to enable the transfer of the functional entity but should also be stable enough to endure storage and the conditions applied during library synthesis. Hence fine tuning of the reactivity for a particular building block is vital. The reactivity of a building block depends partly on the characteristics of the functional entity and the characteristics of the carrier. E.g. a highly reactive functional entity attached to a highly reactive carrier would form a building block that may be susceptible to hydrolysis during the library synthesis thus preventing successful transfer of one functional entity to another. Further, if transfer of a functional entity precursor is faster than coding element—complementing element recognition unspecific reactions may result.
[0072] Therefore, the present invention particularly relates to practically useful library building blocks capable of acting as acylating agents, thioacetylating agents or amidinoylating agents with a balanced reactivity. Such building blocks may be assembled by several different pathways as described below.
[0073] The R group of the Functional entity, may be selected from any transferable chemical group capable of forming a connection to —X(═V)— group. In certain aspects of the invention the functional entity precursor is represented by the formula Z 2 R 17
[0000] wherein Z is absent, O, S or NR 24 . In certain embodiment Z is absent. In a another embodiment Z is O. In still another embodiment Z is S, and in still a further embodiment Z is NR 24 .
[0074] R 17 and R 24 independently is H, alkyl, alkenyl, alkynyl, alkadienyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl, optionally substituted with one or more substituents selected from the group consisting of SnR 18 R 19 , R 20 , Sn(OR 18 )R 19 R 20 , Sn(OR 18 )(OR 19 )R 20 , BR 18 R 19 , B(OR 18 )R 19 , B(OR 18 )(OR 19 ), halogen, CN, CNO, C(halogen) 3 , OR 18 , OC(═O)R 18 , OC(═O)OR 18 , OC(═O)NR 18 R 19 , SR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , N 3 , NR 18 R 19 , N + R 18 R 19 R 20 , NR 18 OR 19 , NR 18 NR 19 R 20 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , NC, P(═O)(OR 18 )OR 19 , P + R 18 R 19 R 20 , C(═O)R 18 , C(═NR 18 )R 19 , C(═NOR 18 )R 19 , C(═NNR 18 R 19 ), C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 , C(═O)NR 18 NR 19 R 20 , C(═NR 18 )NR 19 R 20 , C(═NOR 18 )NR 19 R 20 or R 21 ,
[0000] wherein,
[0075] R 18 , R 19 and R 20 independently is H, alkyl, alkenyl, alkynyl, alkadienyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl, optionally substituted with one or more substituents selected from the group consisting of halogen, CN, CNO, C(halogen) 3 , OR 21 , OC(═O)R 21 , OC(═O)OR 21 , OC(═O)NR 21 R 22 , SR 21 , S(═O)R 21 , S(═O) 2 R 21 , S(═O) 2 NR 21 R 22 , NO 2 , N 3 , NR 21 R 22 , N + R 21 R 22 R 23 , NR 18 OR 19 , NR 18 NR 19 R 20 , NR 21 C(═O)R 22 , NR 21 C(═O)OR 22 , NR 21 C(═O)NR 22 R 23 , NC, P(═O)(OR 21 )OR 22 , P + R 18 R 19 R 20 , C(═O)R 21 , C(═NR 21 )R 22 , C(═NOR 21 )R 22 , C(═NNR 21 R 22 ), C(═O)OR 21 , C(═O)NR 21 R 22 , C(═O)NR 21 OR 22 , C(═NR 18 )NR 19 R 20 , C(═NOR 18 )NR 19 R 20 or C(═O)NR 21 NR 22 R 23 , wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0000] wherein,
[0076] R 21 , R 22 and R 23 independently is H, alkyl, alkenyl, alkynyl, alkadienyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl and wherein R 21 and R 22 may together form a 3-8 membered heterocyclic ring or R 21 and R 23 may together form a 3-8 membered heterocyclic ring or R 22 and R 23 may together form a 3-8 membered heterocyclic ring,
[0077] In a further embodiment,
[0078] R 17 and R 24 independently is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 4 -C 8 alkadienyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl, optionally substituted with one or more substituents selected from the group consisting of SnR 18 R 19 ,R 20 , Sn(OR 18 )R 19 R 20 , Sn(OR 18 )(OR 19 )R 20 , BR 18 R 19 , B(OR 18 )R 19 , B(OR 18 )(OR 19 ), halogen, CN, CNO, C(halogen) 3 , OR 18 , OC(═O)R 18 , OC(═O)OR 18 , OC(═O)NR 18 R 19 , SR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , N 3 , NR 18 R 19 , N + R 18 R 19 R 20 , NR 18 OR 19 , NR 18 NR 19 R 20 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , NC, P(═O)(OR 18 )OR 19 , P + R 18 R 19 R 20 , C(═O)R 18 , C(═NR 18 )R 19 , C(═NOR 18 )R 19 , C(═NNR 18 R 19 ), C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 , C(═O)NR 18 NR 19 R 20 , C(═NR 18 )NR 19 R 20 , C(═NOR 18 )NR 19 R 20 or R 21 ,
[0000] wherein,
[0079] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 4 -C 8 alkadienyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 38 membered heterocyclic ring,
[0080] In another embodiment,
[0081] R 17 and R 24 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl, optionally substituted with one or more substituents selected from the group consisting of halogen, CN, C(halogen) 3 , OR 18 , OC(═O)R 18 , OC(═O)OR 18 , OC(═O)NR 18 R 19 , SR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 OR 19 , NR 18 NR 19 R 20 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , P(═O)(OR 18 )OR 19 , C(═O)R 18 , C(═NR 18 )R 19 , C(═NOR 18 )R 19 , C(═NNR 18 R 19 ), C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 , C(═O)NR 18 NR 19 R 20 , C(═NR 18 )NR 19 R 20 , C(═NOR 18 )NR 19 R 20 or R 21 ,
[0000] wherein,
[0082] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0083] In still another embodiment,
[0084] R 17 and R 24 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl, optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , OC(═O)R 18 , OC(═O)OR 18 , OC(═O)NR 18 R 19 , SR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 OR 19 , NR 18 NR 19 R 21 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , P(═O)(OR 18 )OR 19 , C(═O)R 18 , C(═NR 18 )R 19 , C(═NOR 18 )R 19 , C(═NNR 18 R 19 ), C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 , C(═O)NR 18 NR 19 R 20 , C(═NR 18 )NR 19 R 20 , C(═NOR 18 )NR 19 R 20 or R 21 ,
[0000] wherein,
[0085] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0086] In still another embodiment,
[0087] R 17 and R 24 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl, optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0088] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0089] In still another embodiment,
[0090] R 17 and R 24 independently is H, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, phenyl, naphtyl, thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0091] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0092] In still another embodiment,
[0093] R 17 and R 24 independently is H, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0094] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0095] In still another embodiment,
[0096] R 17 and R 24 independently is H, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0097] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0098] In still another embodiment,
[0099] R 17 and R 24 independently is H, phenyl, naphtyl, thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0100] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 38 membered heterocyclic ring,
[0101] In still another embodiment,
[0102] R 17 and R 24 independently is H, phenyl or naphtyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0103] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0104] In still another embodiment,
[0105] R 17 and R 24 independently is H, thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0106] R 18 , R 19 , R 20 and R 21 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0107] In still another embodiment,
[0108] R 17 and R 24 independently is H, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0109] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0110] In still another embodiment,
[0111] R 17 and R 24 independently is H, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0112] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0113] In still another embodiment,
[0114] R 17 and R 24 independently is H, phenyl, naphtyl, thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0115] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0116] In still another embodiment,
[0117] R 17 and R 24 independently is H, phenyl or naphtyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0118] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0119] In still another embodiment,
[0120] R 17 and R 24 independently is H, thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0121] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0122] In still another embodiment,
[0123] R 17 and R 24 independently is H, methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 19 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0124] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl or butyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0125] In still another embodiment,
[0126] R 17 and R 24 independently is H, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0127] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl or butyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0128] In still another embodiment,
[0129] R 17 and R 24 independently is H, phenyl, naphtyl, thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0130] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl or butyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0131] In still another embodiment,
[0132] R 17 and R 24 independently is H, phenyl or naphtyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0133] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl or butyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0134] In still another embodiment,
[0135] R 17 and R 24 independently is H, thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0136] R 18 , R 19 , R 20 and R 21 independently is H, methyl, ethyl, propyl or butyl and wherein R 18 and R 19 may together form a 3-8 membered heterocyclic ring or R 18 and R 20 may together form a 3-8 membered heterocyclic ring or R 19 and R 20 may together form a 3-8 membered heterocyclic ring,
[0137] In still another embodiment,
[0138] R 17 and R 24 independently is methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0139] R 18 , R 19 , R 20 and R 21 independently is H, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
[0140] In still another embodiment,
[0141] R 17 and R 24 independently is aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 OR 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0142] R 18 , R 19 , R 20 and R 21 independently is H, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
[0143] In still another embodiment,
[0144] R 17 and R 24 independently is phenyl, naphtyl, thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0145] R 18 , R 19 , R 20 and R 21 independently is H, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
[0146] In still another embodiment,
[0147] R 17 and R 24 independently is phenyl or naphtyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0148] R 18 , R 19 , R 20 and R 21 independently is H, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
[0149] In still another embodiment,
[0150] R 17 and R 24 independently is thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 18 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0151] R 18 , R 19 , R 20 and R 21 independently is H, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl,
[0152] In still another embodiment,
[0153] R 17 and R 24 independently is methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0154] R 18 , R 19 , R 20 and R 21 independently is H, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl.
[0155] In still another embodiment,
[0156] R 17 and R 24 independently is aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0157] R 18 , R 19 , R 20 and R 21 independently is H, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl.
[0158] In still another embodiment,
[0159] R 17 and R 24 independently is phenyl, naphtyl, thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0160] R 18 , R 19 , R 20 and R 21 independently is H, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl.
[0161] In still another embodiment,
[0162] R 17 and R 24 independently is phenyl or naphtyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0163] R 18 , R 19 , R 20 and R 21 independently is H, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl.
[0164] In still another embodiment,
[0165] R 17 and R 24 independently is thienyl, furyl, pyridyl, quinolinyl or isoquinolinyl optionally substituted with one or more substituents selected from the group consisting of F, Cl, CN, CF 3 , OR 18 , S(═O)R 18 , S(═O) 2 R 18 , S(═O) 2 NR 18 R 19 , NO 2 , NR 18 R 19 , NR 18 C(═O)R 19 , NR 18 C(═O)OR 19 , NR 18 C(═O)NR 19 R 20 , C(═O)R 18 , C(═NOR 18 )R 19 , C(═O)OR 18 , C(═O)NR 18 R 19 , C(═O)NR 18 OR 19 or R 21 ,
[0000] wherein,
[0166] R 18 , R 19 , R 20 and R 21 independently is H, phenyl, naphthyl, thienyl, furyl, pyridinyl, quinolinyl or isoquinolinyl.
[0167] In still another embodiment,
[0168] R 17 and R 24 independently is H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloheteroalkyl, aryl or heteroaryl
[0169] In still another embodiment,
[0170] R 17 and R 24 independently is H,
[0171] In still another embodiment,
[0172] R 17 and R 24 independently is C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl or C 3 -C 7 cycloheteroalkyl,
[0173] In still another embodiment,
[0174] R 17 and R 24 independently is methyl, ethyl, propyl or butyl
[0175] in still another prefered embodiment
[0176] R 17 and R 24 independently is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl
[0177] in still another prefered embodiment
[0178] R 17 and R 24 independently is aziridinyl, pyrrolidinyl, piperidinyl or morpholinyl
[0179] In still another embodiment,
[0180] R 17 and R 24 independently is aryl or heteroaryl
[0181] In still another embodiment,
[0182] R 17 and R 24 independently is phenyl or naphthyl
[0183] In still another embodiment,
[0184] R 17 and R 24 independently is thienyl, furyl, pyridyl, quinolinyl or isoquinolyl
EXPERIMENTS
[0185] All oligos used were prepared by standard phosphoramidite chemistry and purchased from DNA technology, Denmark. The type II compounds used were commercially available from Fluka (4-pentynoic acid cat. no: 77055, 5-hexynoic acid cat. no: 53108 and N-tertbutoxycarbonyl beta-alanin cat. no: 15382). The hexapeptide used as scaffold was synthesised using standard Fmoc chemistry and protected at the N-terminal by acetylation and at the C-terminal by formamide formation. The protected hexapeptide was commercially available from Schaefer-N, Denmark.
EXAMPLE 1
Preparation of Type I Compound (Method A)
[0186]
[0187] N-hydroxymaleimide (4 mmol) was mixed with Et 3 N (4 mmol) in DCM (15 mL) at 0° C. Acetyl chloride (4 mmol) was added and the reaction mixture was left at rt o/n. DCM (15 mL) was added and the reaction mixture was washed with citric acid (3×30 mL), NaHCO 3 (2×30 mL) and NaCl aq. (30 mL). The organic phase was dried over MgSO 4 and evaporated in vacuo to afford acetic acid 2,5-dioxo-2,5-dihydropyrrol-1-yl ester in 41% yield. 1 H NMR (CDCl 3 ): 6.74 (s, 2H), 2.32 (s, 2H).
EXAMPLE 2
Preparation of Building Blocks (Method A)
[0188]
[0189] A dTS—S—oligo (10 nmol) is evaporated to dryness in vacuo. The oligo is redissolved in DTT (50 μl 100 mM) in 100 mM Sodium-phosphate buffer pH 8.0. Incubate at 37° C. for 1 h and purify using a micro-spin column equilibrated with Hepes-OH (100 mM, pH 7.5). The HS-oligo is treated with CTAB (50 μL, 1 mM) and the mixture is evaporated to dryness in vacuo. The HS-oligo obtained is redissolved in DMF (100 μL) and treated with compounds of type I (100 μl 100 mM in DMF) for 3 h at rt. NaOAc (200 μl 1 M, pH=7.5) is added and the reaction mixture is extracted with EtOAc (2×300 μL). The loaded oligo is finally purified using a micro-spin column equilibrated with Hepes-OH (100 mM, pH 7.5).
EXAMPLE 3
Preparation of Building Blocks (Method B)
[0190]
[0191] C 6 S-S-oligonucleotides A to D (10 nmol) is evaporated to dryness in vacuo.
A: 5′-GCG ACC TGG AGC ATC CAT CGT S B: 5′-GAG CAT CCA TCG S C: 5′-GAC GAG CAT CCA TCG S D: 5′-CTA GGG ACG AGC ATC CAT CGS S=Thiol C6 SS modifier (Glen# 10-1936)
[0197] The oligo is redissolved in DTT (50 μl 100 mM ) in 100 mM Sodium-phosphate pH 8.0. Incubate at 37° C. for 1 h and purify using a micro-spin column equilibrated with Hepes-OH (100 mM, pH 7.5). NHM (50 μl 100 mM) in HepesOH (100 mM, pH 7.5) is added to the obtained HS-oligo and the mixture is incubated at 25° C. for 2 h. The oligo-S-NHS is then purified using a Microspin columns equilibrated in MS-grade H 2 O and analysed by ES-MS.
A: MS (calc): 6723.52; MS (found): 6723.21 B: MS (calc): 3938.75; MS (found): 3937.78 C: MS (calc): 4870.36; MS (found): 4869.42 D: MS (calc): 6435.38; MS (found): 6434.57
[0202] Four EDC-activated compounds were prepared by mixing 50 μl 100 mM of each of the compounds (acetic acid, 4-pentynoic acid, N-tertbutoxycarbonyl beta-alanine, and 5-hexynoic acid) in DMF with 50 μl 100 mM of EDC in DMF and leave the mixture at rt for 30 min before use. Subsequently, each of the oligo-S-NHS (1 nmol) is redissolved in MES-buffer (10 μl 100 mM, pH 6) and treated with 10 μl of a DMF solution of the EDC-activated compounds. After 1 h the building blocks are purified using a microspin column equilibrated with 100 mM MES pH6 to obtain
oligonucleotide A loaded with acetyl, oligonucleotide B loaded with 4-pentynyl (=FE 1 ), oligonucleotide C loaded with N-tertbutoxycarbonyl beta-alaninyl (=FE 2 ), and oligonucleotide D loaded with 5-hexynyl (FE 3 ).
[0207] ES-MS analysis of the loaded oligonucleotides showed the masses of their corresponding oligo-S-NHS-building blocks shown above, due to the presence of piperidine added during analysis.
EXAMPLE 4
Preparation of Scaffold Building Blocks
[0208]
[0209] 10 nmol of the amino-oligo was diluted in 160 μL 100 mM Hepes-KOH buffer pH 7.5. N-Succinimidyl 3-[2-pyridyldithio]-propionamido, SPDP (40 μl 20 mM, Pierce cat # 21857) was added and the mixture was incubated for 2 h at 30° C. The oligo was extracted with ethyl acetate (200 μL) and purified using micro spin columns equilibrated with 100 mM Hepes-KOH buffer pH 7,5. The hexapeptide CysPhePheLysLysLys (10 μl 100 mM) was added and the mixture was incubated over-night at 30° C. The oligo was purified by ammoniumacetate precipitation and analysed by ES-MS.
[0210] MS (calc): 8386.41; MS (found): 8386.57
[0211] Used oligo:
E: 5′-X CGA TGG ATG CTC GTC CCT AGA YZ X=5′-amino modifier C 6 (Glen# 10-1926) Y=PC spacer (Glen# 104913) Z=Biotin phosphoramidite (Glen# 10-1955)
EXAMPLE 5
Transfer of a Functional Entity
[0216]
[0217] Oligonucleotide A loaded with acetyl (250 pmol) was added to oligo F (200 pmol) in 50 μl 100 mM MES, pH 6. The mixture was incubated overnight at 25° C. Subsequently, the mixture was purified by gel filtration using a microspin column equilibrated with H 2 O and transfer of the functional entity was verified by electron spray mass spectrometry (ES-MS).
[0218] Used oligos:
A: 5′-GCG ACC TGG AGC ATC CAT CGT-acetyl F: 5′-X ACG ATG GAT GCT CCA GGT CGC X=5′ Amino-modifier C 6 (Glen# 10-1906)
[0222] MS (calc): 6667.46; MS (found) 6666.64.
EXAMPLE 6
Transfer of a Three Different Functional Entities
[0223]
[0224] Transfer of the first functional entity: Scaffold building block oligo E (400 pmol) was added to oligo B (400 pmol in 25 μl MES buffer, pH 6), loaded with 4-pentynyl, and incubated over-night at 15° C. The volume was then adjusted to 50 μl and the mixture transferred to a streptavidin-bead slurry (Pharmacia cat #17-5113-01, prewashed with 100 ul MES buffer) and incubated for 10 min at room-temperature, followed by incubation on ice for 10 min. The beads were washed four times with ddH 2 O, resuspended in 100 μl 10 mM NaOH and incubated for 2 min at room temperature to denature the duplex. The NaOH was removed and the beads were subsequently washed twice with 60° C. ddH 2 O. The water was removed and the beads resuspended in 25 μl 100 mM MES buffer pH 6.0.
[0225] Transfer of the second functional entity: Oligo C (400 pmol in 25 μl MES buffer, pH 6), loaded with N-tertbutoxycarbonyl beta-alaninyl, was added to the beads and the mixture was incubated at 25° C. for 2 h. The beads were washed four times with ddH 2 O, resuspended in 100 μl 10 mM NaOH and incubated for 2 min at room temperature to denature the duplex. The NaOH was removed and the beads were subsequently washed twice with 60° C. ddH 2 O. The water was removed and the beads resuspended in 25 μl 100 mM MES buffer pH 6.0.
[0226] Transfer of the third functional entity: Oligo D (400 pmol in 25 μl MES buffer, pH 6), loaded with 5-hexynyl, was added to the beads and the mixture was incubated at 25° C. for 2 h. The beads were washed four times with ddH 2 O, resuspended in 100 μl 10 mM NaOH and incubated for 2 min at room temperature to denature the duplex. The NaOH was removed and the beads were subsequently washed twice with 60° C. ddH 2 O. The beads were additionally washed once with 50 μl MES buffer and twice with 50 μL water. The beads were resuspended in 25 μl ddH 2 O and put on UV transilluminator for 2×15 seconds to cleave oligo E from the beads. 25 μl 12% ammonia was added and the mixture was incubated for 5 min at 50° C. The sample was spun twice at 5 kG, and the supernatant collected. The sample was evaporated to dryness in vacuo, and analysed by ES-MS.
MS of the trisubstituted product (calc): 8197.17 MS of the trisubstituted product (found): 8196.80
EXAMPLE 7
Attachment of Functional Entity to a Thio Oligo
[0229] The following oligos containing a nucleobase modified with a S-triphenylmethyl protected thio moiety, were synthesised using the conventional phosphoramidite approach:
L: 5′- W CA TTG ACC TGA ACC ATG BTA AGC TGC CTG TCA GTC GGT ACT ACG ACT ACG TTC AGG CAA GA M: 5′- W CA TTG ACC TGA ACC ATG TBA AGC TGC CTG TCA GTC GGT ACT TCA AGG ATC CAC GTG ACC AG
[0230] W was incorporated using the commercially available thiol modifier phosphoramidite (10-1926-90 from Glen research). B is an internal biotin incorporated using the commercially available phosphoramidite (10-1953-95 from Glen research).
[0231] To make an SH group available for further reaction, the S-triphenylmethyl protected thio oligo (10 nmol) was evaporated in vacuo and resuspended in TEAA buffer (200 uL of a 0.1 M solution, pH=6.4). AgNO 3 (30 uL of a 1 M solution) was added and the mixture was left at room temperature for 1-2 hours. DTT (46 uL of a 1M solution) was added and left for 5-10 minutes. The reaction mixture was spun down (20.000 G for 20 minutes) and the supernatant was collected. The solid was extracted with additional TEAA buffer (100 ul of a 0.1 M solution, pH=6.4). The pure thio oligo was obtained by conventional EtOH-precipitation.
[0232] The L oligo was subsequently reacted with the compound
forming a building block able to transfer an acetyl group to a nucleophilic group like an amine, and the M oligo was reacted with the compound
forming a building block capable of transferring a 3-tertbutoxycarbonylamino-butanyl group to a nucleophilic recipient group.
[0233] The reaction may be represented by the reaction scheme:
[0234] General procedure: The thio oligo (1 nmol) was dried in vacuo and treated with the NHS compound shown above in dimethylformamide (50 ul of a 0.1 M solution) and left o/n at rt. The thio oligo was spun down (20.000 G for 10 minutes) and the supernatant removed. Dimethylformamide (1 mL) was added and the loaded thio oligo was spun down (20.000 G for 10 minutes). The dimethylformamide was removed and the loaded thio oligo was resuspended in TEAA buffer (25 uL of a 0.1M solution, pH=6.4) and analysed by HPLC.
[0235] The functional entities were transferred to a amino oligonucleotide according to the scheme:
[0236] General procedure: The template oligo 5′-BTCTTGCCTGAACGTAGTCGTAGGTCGATCCGCGTTACCAGAGCTGGATGCTC GACAGGTCCCGATGCAATCCAGAGGTCG (1 nmol) was mixed with the oligos (L or M) loaded with a functional entity (1 nmol) and amino oligo O in hepes-buffer (20 uL of a 100 mM HEPES and 1 M NaCl solution, pH=7.5) and water (added to a final volume of 100 uL). The oligos were annealed to the template by heating to 50° C. and cooled (−2° C./30 second) to 30° C. The mixture was then left o/n at a fluctuating temperature (10° C. for 1 second then 35° C. for 1 second). The oligo complex was attached to streptavidine by addition of streptavidine beads (100 uL, prewashed with 2×1 mL 100 mM hepes buffer and 1M NaCl, pH=7.5). The beads were washed with hepes buffer (1 mL). The amino oligo was separated from the streptavidine bound complex by addition of water (200 uL) followed by heating to 70° C. for 1 minute. The water was transferred and evaporated in vacuo, resuspended in TEAA buffer (45 uL of a 0.1 M solution) and product formation analysed by HPLC (see FIG. 5 ).
[0237] FIG. 5 shows the transfer of functional entities to an oligo containing a modified nucleobase with an amino group.
A) The top chromatogram show the reference amino oligo O: 5′-GAC CTG TCG AGC ATC CAG CTT CAT GGC TGA GTC CAC AAT GZ. Z contain the modified nucleobase with an aminogroup, incorporated using the commercially available amino modifier C6 dT phosphoramidite (10-1039-90 from Glen research). B) The middle chromatogram show the streptavidine purified amino oligo O after partial transfer of a acetyl group from oligo L. C) The bottom chromatogram show the streptavidine purified amino oligo O after the complete transfer of the more lipophilic 3-tertbutoxycarbonylamino-butanyl. The following gradient was used in the obtainment of the chromatograms: 0-3 minutes 100% A then 15% A and 85% B from 3-10 minutes.
[0241] The experiment where the template oligo was omitted showed no non-templated product formation. The results indicate that the efficiency of the templated synthesis was 80-100%. The reason for less than 100% efficiency was probably due to hydrolytic cleavage of the functional entity.
EXAMPLE 8
Simultaneous Transfer of Two Functional Entities
[0242] The following oligo containing a nucleobase modified with a carboxylic acid moiety, was synthesised using the conventional phosphoramidite approach:
H: 5′-GAC CTG TCG AGC ATC CAG CTT CAT GGG AAT TCC TCG TCC A CA ATG XT
[0243] X was incorporated using the commercially available carboxy-dT phosphoramidite (10-1035-90 from Glen research).
[0244] The modified oligo was provided with a trisamine scaffold according to the scheme:
[0245] Procedure: The modified oligo (1 nmol) was mixed with water (100 uL), hepes buffer (40 uL of a 200 mM, pH=7.5), NHS (20 uL of a 100 mM solution), EDC (20 uL of a freshly prepared 1 M solution) and the tetraamine tetrakis(aminomethyl)methane tetrahydrochloride (20 uL of a 100 mM solution). The reaction mixture was left o/n at room temperature. The volume was reduced to 60 uL by evaporation in vacuo. The pure oligo was obtained by addition of NH 3 conc. (20 uL) followed by HPLC purification. It was possible to isolate a peak after approximately 6 min using the following gradient: 0-3 minutes 100% A then 15% A and 85% B from 3-10 minutes then 100% B from 10-15 minutes then 100% A from 15-20 minutes. A=2% acetonitrile in 10 mM TEAA and B=80% acetonitrile in 10 mM TEAA.
[0246] The following oligos containing a nucleobase modified with a S-triphenylmethyl protected thio moiety, was synthesised using the conventional phosphoramidite approach:
K: 5′- W C A TTG ACC TGT CTG CCB TGT CAG TCG GTA CTG TGG TAA CGC GGA TCG ACC T L: 5′- W CA TTG ACC TGA ACC ATG BTA AGC TGC CTG TCA GTC GGT ACT ACG ACT ACG TTC AGG CAA GA
[0247] W was incorporated using the commercially available thiol modifier phosphoramidite (10-1926-90 from Glen research). B is an internal biotin incorporated using the commercially available phosphoramidite (10-1953-95 from Glen research).
[0248] To make an SH group available for further reaction, the S-triphenylmethyl protected thio oligo (10 nmol) was evaporated in vacuo and resuspended in TEAA buffer (200 uL of a 0.1M solution, pH=6.4). AgNO 3 (30 uL of a 1 M solution) was added and the mixture was left at room temperature for 1-2 hours. DTT (46 uL of a 1 M solution) was added and left for 5-10 minutes. The reaction mixture was spun down (20.000 G for 20 minutes) and the supernatant was collected. The solid was extracted with additional TEAA buffer (100 ul of a 0.1.M solution, pH=6.4). The pure thio oligo was obtained by conventional EtOH-precipitation.
[0249] The K and L oligo was subsequently reacted with the compound
forming a building block capable of transferring the lipophilic S-Trityl-4-mercaptobenzoyl group to a recipient nucleophilic group.
[0250] The transfer reaction is schematically represented below:
[0251] The template oligo 5′-BTCTTGCCTGAACGTAGTCGTAGGTCGATCCGCGTTACCAGAGCTGGATGCTC GACAGGTCCCGATGCAATCCAGAGGTCG (1 nmol) was mixed with the two thio oligos (K and L) loaded with the same functional entity (S-Trityl-4-mercaptobenzoyl; 1 nmol) and the trisamine oligo H (1 nmol) in hepes-buffer (20 uL of a 100 mM hepes and 1 M NaCl solution, pH=7.5) and water (added to a final volume of 100 uL). The oligos were annealed to the template by heating to 50° C. and cooled (−2° C./30 second) to 30° C. The mixture was then left o/n at a fluctuating temperature (10° C. for 1 second then 35° C. for 1 second). The oligo complex was attached to streptavidine by addition of streptavidine beads (100 uL, prewashed with 2×1 mL 100 mM hepes buffer and 1M NaCl, pH=7.5). The beads were washed with hepes buffer (1 mL). The trisamine scaffold oligo H was separated from the streptavidine bound complex by addition of water (200 uL) followed by heating to 70° C. The water was transferred and evaporated in vacuo, resuspended in TEAA buffer (45 uL of a 0.1 M solution) and product formation analysed by HPLC (see FIG. 6 ).
[0252] The HPLC chromatogram shows the transfer of two functional entities to a scaffold oligo with three amino groups.
A) The top chromatogram shows the reference scaffold oligo H. B) The bottom chromatogram show the streptavidine purified scaffold oligo H after the partial transfer of one (peak at 7.94 minutes) and two (peak at 10.76 minutes) identical functional entities (S-Trityl-4-mercaptobenzoyl). The following gradient was used: 0-3 minutes 100% A, then 15% A, and 85% B from 3-10 minutes then 100% B from 10-15 minutes. A=2% acetonitrile in 10 mM TEAA and B=80% acetonitrile in 10 mM TEAA.
[0255] Due to the lipophilic nature of the functional entities a longer retention time, in the HPLC chromatogram of the scaffolded molecule with two functional entities compared to one functional entity, was observed. The efficiency of the templated synthesis of a scaffolded molecule with the two identical functional entities was about 25% (peak at 10.76 minutes in FIG. 6 ).
Model Example 1
[0256] General route to the formation of acylating building blocks and the use of these:
[0257] N-hydroxymaleimide (1) may be acylated by the use of an acylchloride e.g. acetyl-chloride or alternatively acylated in e.g. THF by the use of dicyclohexylcarbodiimide or diisopropylcarbodiimide and acid e.g. acetic acid. The intermediate may be subjected to Michael addition by the use of excess 1,3-propanedithiol, followed by reaction with either 4,4′-dipyridyl disulfide or 2,2′-dipyridyl disulfide. This intermediate (3) may then be loaded onto an oligonucleotide carrying a thiol handle to generate the building block (4). The reaction of this building block with an amine carrying scaffold is conducted as follows:
[0258] The template oligonucleotide (1 nmol) is mixed with a thio oligonucleotide building block e.g. (4) (1 nmol) and an amino-oligonucleotide scaffold (1 nmol) in hepes-buffer (20 μL of a 100 mM hepes and 1 M NaCl solution, pH=7.5) and water (39 uL). The oligonucleotides are annealed to the template by heating to 50° C. and cooling (2° C./second) to 30° C. The mixture is then left o/n at a fluctuating temperature (10° C. for 1 second then 35° C. for 1 second), to yield template bound (5).
[0259] The above examples are intended to help illustrate the invention, and are not intended to, nor should they be construed to, limit the scope of the invention. Indeed, various modifications of the invention and many further embodiments thereof, in addition to those shown and described herein, will become apparent to those skilled in the art from the full content of this document, including the examples shown above and the references to the scientific a patent literature cited herein. It should further be appreciated that the contents of those cited references are incorporated herein by reference to help illustrate the state of the art. The examples above contain important additional information that can be adapted to the practice of this invention in its various embodiments and the equivalents thereof.
Abbreviations DCC N,N′-Dicyclohexylcarbodiimide DhbtOH 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine DIC Diisopropylcarbodiimide DIEA Diethylisopropylamin DMAP 4-Dimethylaminopyridine DNA Deoxyribosenucleic Acid EDC 1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide.HCl HATU 2-(1H-7-Azabenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate HBTU 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate HOAt N-Hydroxy-7-azabenzotriazole HOBt N-Hydroxybenzotriazole LNA Locked Nucleic Acid NHS N-hydroxysuccinimid OTf Trifluoromethylsulfonate OTs Toluenesulfonate PNA Peptide Nucleic Acid PyBoP Benzotriazole-1-yl-oxy-tris-pyrrolidino- phosphonium hexafluorophosphate PyBroP Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate RNA Ribonucleic acid TBTU 2-(1H-Benzotriazole-1-yl)-1,1,3,3- tetramethyluronium tetrafluoroborate TEA Triethylamine RP-HPLC Reverse Phase High Performance Liquid Chromatography TBDMS-Cl Tert-Butyldimethylsilylchloride 5-Iodo-dU 5-iodo-deoxyriboseuracil TLC Thin layer chromatography (Boc) 2 O Boc anhydride, di-tert-butyl dicarbonate TBAF Tetrabutylammonium fluoride SPDP Succinimidyl-propyl-2-dithiopyridyl CTAB Cetylammoniumbromide
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A building block having the dual capabilities of transferring the genetic information e.g. by recognising an encoding element and transferring a functional entity to a recipient reactive group is diclosed. The building block can be designed with an adjustable transferability taking into account the components of the building block. The building block may be used in the generation of a single complex or libraries of different complexes, wherein the complex comprises an encoded molecule linked to an encoding element. Libraries of complexes are useful in the quest for pharmaceutically active compounds.
| 2 |
This is a division of U.S. patent application Ser. No. 562,583, filed Aug. 3, 1990, now U.S. Pat. No. 5,059,730, which is a divisional of Ser. No. 230,497, filed Aug. 10, 1988, now U.S. Pat. No. 4,960,201.
BACKGROUND AND SUMMARY OF THE INVENTION
The present invention relates to conveyor systems and, more particularly, to dump-type conveyor systems having driver members attached to an endless belt to move workpieces along a workpiece transporting table. The invention further provides a pivotal movement of conveyor sections such that one end of the conveyor is movable with respect to the other end of the conveyor.
In the conveyor field, there is a difficulty with moving workpieces that have a radially extending base with an elongated axial projection such as some gear configurations. Generally, the workpieces are positioned on a conveyor such that they are resting on their base with the projection extending vertically upward. For some workpiece configurations, this positioning makes them unstable and susceptible to tipping, which particularly becomes a problem if the parts become stacked at the end of the conveyor. Accordingly, there is a need in the field to provide an improved conveyor system to handle workpieces of the configuration discussed above.
The present invention provides a conveyor system that conveniently handles workpieces having elongated projecting portions with a radially extending base. The present invention enables such workpieces to be positioned on the conveyor with the radially extending base supported by bearing elements with the projecting portion oriented downwardly. Due to this manner of supporting the workpiece, the present invention enables such workpieces to be stacked at the end of the conveyor during holding while reducing the tendency of the workpieces to tip. Further, the present invention provides the art with a sectional conveyor system which enables the sections to be pivoted with respect to one another, making the conveyor adjustable and adaptable for various plant layouts.
The conveyor system according to this invention includes a workpiece transport mechanism to support the workpieces as they are moved along the conveyor system. The transport mechanism has a receiving end and a removal or holding end. An endless moving belt is positioned below a transport mechanism which supports the parts. A driver mechanism is coupled to the endless belt which acts on the downwardly extending projecting portion of the workpieces to drive them along the transport mechanism. Also, a hinging system couples sections of the workpiece transport mechanism and the endless conveyor belt to enable angular movement of conveyor sections.
From the subsequent detailed description and appended claims taken in conjunction with the accompanying drawings, other objects and advantages of the present invention will become apparent to those skilled in the art.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a conveyor system in accordance with the present invention.
FIG. 2 is a partial elevation view of an end of the conveyor system in accordance with the present invention.
FIG. 3 is a top plan view between two sections of a conveyor system in accordance with the present invention.
FIG. 4 is a partial perspective view of a removal or holding end of a conveyor system in accordance with the present invention.
FIG. 5 is a perspective view of a driver in accordance with the present invention.
FIG. 6 is a top plan view similar to FIG. 3, illustrating the pivotal movement of the sections.
FIG. 7 is a perspective view of another driver in accordance with the present invention.
FIG. 8 is a perspective view of another driver in accordance with the present invention.
FIG. 9 is a side elevation view partially in cross-sections of another embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Moving to the Figures, and particularly to FIG. 1, a conveyor system is illustrated and designated with the reference numeral 10. The conveyor system 10 includes a first conveying portion 12 and a second conveying portion 14. Generally, workpieces are placed onto the conveyor system at the first portion 12 and are removed from the conveying system at the end of the second portion 14. However, this could be reversed.
The conveyor sections 12 and 14 are comprised of workpiece transfer sections 16 and 18 coupled with endless belt support sections 20 and 22, all of which are positioned above the ground by legs 24. A number of driver mechanisms 26 are attached to the endless belt 28 for driving workpieces 30 along the workpiece transfer sections 16 and 18.
Turning to FIGS. 2 through 4, a better understanding of the present invention may be acquired. The transfer section mechanisms 16 and 18 are substantially the same, and the same reference numerals will be used to identify similar elements. The transfer mechanism sections 16 and 18 include a pair of wall members 32 and 34. The wall members 32 and 34 are positioned opposing one another such that a channel 36 is formed between them. A plurality of bearing rollers 38 are positioned on one of the longitudinal edges of both of the wall members 32 and 34, forming a channel 37 between opposing rollers 38. The rollers 38 enable the workpieces 30 to move smoothly along through both sections 16 and 18 of the transfer mechanism although slide bar devices would work with equal success. Struts 40 are positioned at the other longitudinal edge of the wall members 32 and 34 to maintain a consistent channel spacing between the opposing wall members 32 and 34 and rollers 38.
The transfer mechanism sections 16 and 18 are connected together by a flexible transfer section 15. The flexible transfer section 15 is continuous with the sections 16 and 18, however, the flexible transfer section 15 enables the sections 16 and 18 to be pivoted with respect to one another, as seen in FIGS. 3 and 6. The flexible transfer section 15 includes wall members 33 and 35 which are similar to wall members 32 and 34 and are formed of a material such as so called "blue steel", which provides for the flexure of the transfer section 15 to accommodate pivoting of the transfer sections 16 and 18. Rollers 38 are positioned on one longitudinal edge of each of said wall 33 and 35 to enable workpieces 30 to move along the rollers from section 16 to section 18.
The endless belt support sections 20 and 22 are substantially identical, and similar elements will be identified with the same reference numeral. A frame 42 having legs 24 projecting therefrom enables the belt 28 to be moved along the conveyor system 10 A cage 45 is connected to the frame and surrounds the belt 28 to minimize lateral movement of the belt 28. The frame 42 may be hollow or solid depending upon the desires of the end user. Preferably, the frame 42 will be somewhat lightweight to enable movement of section 22 with respect to section 20. The belt 28 moves along the frame sections 42 in the cage 45 and is driven by a motor 44. The cage 45 is on both sides of the frame sections 42 to retain the belt 28 in close proximity with the frame sections 42. The belt 28 reverses directions via sprockets 46 and 48, as seen in FIG. 1. The belt 28, therefore, rides in cage 45 on both longitudinal sides of the frame 42.
Spacer bars 50 are welded or the like to the frame 42 and project upwards and are bolted or the like onto the wall members 32 and 34 of the transfer section 16 and 18. The spacer bars 50 spatially position the workpieces 30 a desired distance from the drivers 26 as they pass along the belt 28. The spacers 50 are located on both lateral sides of the frame 42. Preferably, the struts 40 are positioned through the wall members 32 and 34 and bolted to the spacers 50. A gap or channel 52 is formed between the transfer sections 16 and 18 and the frame sections 20 and 22 to enable the drivers 26 to pass between the transfer sections 16 and 18, and frame sections 20 and 22, as best seen in FIG. 2.
The driver 26, which engages workpieces 30 is best shown in FIG. 5 and includes a pair of pivot arms 54 and 56 for interconnecting the driver to chain 28. A counterbalance 60 is integrally formed with the arms 54 and 56. A bearing 62 is supported by support arms 64 and 66 at a desired angle and height away from and above the counterbalance 60 to contact the workpiece 30 as the drivers 26 pass by the workpieces 30, as seen in FIGS. 2 and 4.
FIGS. 7 and 8 illustrate other embodiments of the driver 26.
The driver 26 illustrated in FIG. 7 has an integral body with a counterweight portion 110 and a pair of side rails 112 and 114. The rails 112 and 114 are integrally formed with and extend substantially transverse to the counterbalance portion 110. An opening is formed between the rails 112 and 114 enabling rollers 116 to span between the rails 112 and 114. A bolt 118 or the like is positioned through the rollers 116 to secure the rollers 116 to the rails 112 and 114.
A post 120 projects from the chain 28. The post 120 enables the driver 26 to be secured to the chain 28. A bolt 122 is passed through an aperture in the post 120. Spacers 124 are positioned between the post 120 and the rails 112 and 114 to enable proper positioning of the driver 26 on the chain 28.
The driver in FIG. 8 is similar to the driver 26 of FIG. 7. The driver in FIG. 8 includes a body member having a counterbalance portion 130 and a pair of side rails 132 and 134. The side rails 132 and 134 are integrally formed with the counterbalance portion 130 and are angular. Rollers 136 are positioned between the side rails 132 and 134 to contact the workpieces. A pin 138 secures the rollers 136 to the side rails 132 and 134.
A second pin 140 is passed through the post 120 to enable securement of the driver onto the chain 28. Spacers 142 are positioned between the post 120 and the rails 132 and 134 to enable proper positioning of the driver on the chain 28. The chain 28 may include magnetic members or the like for magnetically or the like drawing the counterbalance portions of the drivers to the chain 28.
Preferably, a plurality of drivers 26 are spatially positioned on the chain 28 to drive workpieces 30 along the system 10, as best seen in FIGS. 3 and 4. Thus, as a driver bearing 62 comes in contact with the elongated portion 68 of the workpiece 30, the workpiece 30 is driven along the rollers 38 in the transfer sections 15, 16, and 18. As the workpiece 30 contacts the stop 70, the driver 26 pivots on pivot arms 54 and 56 and counterweight 60 moves upward enabling bearing 62 to pass underneath the elongated portion 68 of the workpiece 30 and to continue along with the belt 28. Once the driver 26 is passed the workpiece 30, the counterbalance 60 brings the driver back to an upright position. It should be noted that the drivers 26 will pass under the workpieces as described above at any time the workpiece becomes stopped or detained on the transfer sections.
The stop 70 is positioned between wall members 32 and 34 at the removal end of the conveyor system 10 at transfer section 18. The stop mechanism 70 includes a pivotable member 72 to contact the workpiece 30 to enable the workpieces 30 to be stacked in position along the conveyor and metered out at the desired rate. As the pivot member 72 is moved, the workpiece 30 passes to a position where it can be removed from the conveyor system 10. It should be noted that other stops and feeders known in the art would function satisfactorily.
As can be seen in FIG. 4, the workpieces abut one another at their flange 74 at the removal end of the conveyor. The flange to flange contact of the workpieces with the projecting portion 6 projecting through the roller channel 37 enable the workpieces to be "stacked" in a manner which substantially eliminates the tendency of the workpieces to tip. Thus, the workpieces may be stacked at the removal end of the conveyor and may be removed when needed without the operator being concerned with the workpieces tipping.
The conveyor system 10 includes hinge mechanism 80 at flexible transfer section 15 which enables relative angular movement of the sections 12 and 14 with respect to one another. The mechanism 80 includes arms 81, 82, and 83 coupled with the frame sections 42, which enable coupling of disk members 84 and 86 with the belt 28 at the pivot point of the system 10. Arms 81, 82, and 83 are welded to frames 42 of sections 20 and 22 such that arm 82 projects from frame section 20 between arm 81, and arm 83 projects from frame section 22 so that the arms 81, 82, and 83 mesh, enabling a shaft 88 to be passed therethrough to provide pivotal movement of one conveyor section 12 with respect to the other conveyor section 14
The disks 84 and 86, attached to shaft 88, enable the belt 28 to ride thereon to continue travelling in the cage 45 on the frame sections 42. The disks 84 and 86 are substantially identical to those described in U.S. patent application Ser. No. 856,801, filed Apr. 28, 1986, entitled "Storage Conveyor System", assigned to the same assignee as the present invention, the specification of which is herein incorporated by reference. The disks 84 and 86 provide the belt 28 with continuous movement along the conveyor system 10.
Moving to FIG. 6, the pivotinq of the sections 12 and 14 is shown. As section 14 is pivoted with respect to section 12, the arms 81 and 83 pivot with respect to arm 82 and enable the section 14 to be moved. Also, flexible transfer section 15 flexes to enable the pivoting. As sections 12 and 14 pivot, the belt 28 stays in constant contact on the turn disks 84 and 86 to provide continuous movement of the belt 28 in the conveyor system 10.
FIG. 9 illustrates another embodiment of the present invention. The present invention may be used as a storage-type conveyor to temporarily hold workpieces between work stations until the workpiece can be transported.
As seen in FIG. 9, the storage conveyor system 200 includes a frame 212, a plurality of inclined alternating direction tracks 214, turn disks 216 and at least one or more axles 218 for positioning the disk and the belt 28. The tracks 214 are substantially the same as those described herein having a pair of wall members 220 and 222 positioned opposing one another such that a channel is formed between them. A plurality of bearing rollers 226 are positioned on one of the longitudinal edges of both of the wall members forming a channel between the opposing rollers. The rollers enable the workpiece 30 to move smoothly along the inclined tracks 214.
As mentioned above, the drivers 26 carry the workpieces 30 along the incline tracks 214. The storage conveyor is similar to that disclosed in U.S. patent application No. 856,801, filed Apr. 28, 1986, assigned to the same assignee as the present invention, the specification of which is herein incorporated by reference, and includes modifications including the wall members 222 and 224 and the rollers 226 to carry the workpieces 30 as described herein.
While the above discloses the preferred embodiment of the present invention, it will be understood that modifications, variations and alterations may be made to the present invention without varying from the scope and fair meaning of the subjoined claims.
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A conveyor system enabling dumping of workpieces is disclosed. The conveyor system is comprised of a mechanism for transporting workpieces along the conveyor system. The transporting mechanism has a first receiving end and a second removal or holding end. An endless belt mechanism is coupled with the transport mechanism in a spaced relationship. A driver is coupled with the endless belt in a spaced relationship with the transport mechanism to drive workpieces along the transport mechanism. A mechanism is coupled with the transport mechanism and belt mechanism to enable movement of the removing or holding end of the conveyor system with respect to the receiving end such that the conveyor may be used to feed more than one installation.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] Not applicable to this application.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not applicable to this application.
BACKGROUND OF THE INVENTION
[0003] 1. Field of the Invention
[0004] The present invention relates generally to the decontamination of biological agents. More specifically, the present invention provides a method and apparatus to destroy biological agents such as Anthrax carried in the mail.
[0005] 2. Description of the Prior Art
[0006] Biological warfare, also known as bioterrorism, is the intentional use of organisms to harm or kill people. Terrorists are most likely to use organisms that cause infectious diseases because they are easily spread among people. Disease causing organisms include Yersinia pestis (bubonic plague), tularemia (a plague like bacterial infection), clostridium botulinum (botulism) and tuberculosis but are unlikely to cause widespread disease because they are difficult to manufacture and distribute. Smallpox is more likely choice for bioterrorism since it can spread very rapidly from person to person. Smallpox is passed when infected people sneeze, spraying fine droplets of the virus into the air or through direct contact such as close contact or kissing. Experts on biological warfare regard the bacterium Bacillus anthraces (anthrax) as the biggest hazard.
[0007] Microbiologists consider anthrax a serious hazard because it has characteristics that make it suitable as a weapon. It is produced easily and is readily available around the world. The spores do not require special handling procedures so terrorists could take anthrax to many points for distribution. Unlike other infectious agents such as smallpox, the anthrax spores can survive severe heat and cold. Anthrax can infect people through superficial cuts or wounds, the intestine after the consumption of infected food and the lungs after inhalation of spores.
[0008] An early diagnosis of anthrax is difficult where the symptoms are similar to those seen with flu; fever, chills and muscle aches. Anthrax resulting from inhalation of spores is the form of illness that would likely occur with a bioterrorist attack and would initially resemble a viral respiratory illness and then would progress to severe shortness of breath and hypoxia, a low concentration of oxygen in the blood.
[0009] Following the attack and destruction of the World Trade Center in New York, anthrax has been detected in the mail directed to prominent United States citizens and postal facilities. Whereas the addressee was not affected, other people have died from the disease suspected to be contracted through cross-contaminated mail. The Washington Post newspaper article, dated Dec. 3, 2001, reported “A letter apparently mailed to an address near the Bronx home of anthrax victim Kathy Nguyen passed through the same New Jersey postal sorting machine within seconds of the anthrax-laced letter sent to Sen. Patrick J. Leahy (D-Vt.), officials said yesterday.” Even though none of the workers at the sorting facility had symptoms of cutaneous or inhalation anthrax or unusual absences, cross-contamination through the mail remains a serious threat to anyone that comes in contact with the mail.
[0010] There are several known methods to kill the anthrax bacterial spores. The spores can be incinerated; therefore, suspicious mail can be simply burned. The toxic chlorine dioxide gas was used to kill the mail delivered spores in U.S. Senator Daschle's office suite and liquid or foam decontaminant in the offices of 11 other senators. The gas was pumped into the office and left in place for 20 hours to be followed by another chemical to remove the gas with tests to ensure that no trace remained. The U.S. Postal Service (USPS) is sending mail to be sterilized by electron-beam machines. These machines were originally designed to sterilize medical devices and to get rid of germs in food products. The USPS is purchasing several of these machines at $5 million each for installation at the mail sorting centers to be used on person-to-person and consumer-to-business mail which account for some 40 billion pieces of mail each year. Sandia National Laboratories, operated by Lockheed Martin Co. for the U.S. Department of Energy, has created environment friendly decontamination foam that kills anthrax spores. This product is a chemical cocktail that includes an ingredient that essentially breaks the spore's armor and then another chemical destroys the material inside. Several commercial firms use the Sandia decontaminant in several products intended for home and office use. They provide a hand-washing solution to be used as a daily protective for the post office and general public.
[0011] Doctors have little experience treating anthrax on the scale of a biological attack so it is difficult to predict exactly what might happen. However, the medical community addresses the clinical recognition and management of suspected bioterrorism events through state and national level publications. Anthrax may be successfully treated with an antibiotic if anthrax is identified as the agent of disease and people that were exposed receive prompt treatment. Effective antibiotics, administered on a 60 day course, include ciprofloxacin (Cipro), doxycycline and amoxiclin.
[0012] Currently, there is little the general public can do to guard against contracting the anthrax disease where exposure through mail delivery is the greatest threat. Authorities publish that early detection, handled by public health authorities rather than individuals, is the best defense against widespread disease. The public is encouraged to stay informed through announcements by local public health officials. The Centers for Disease Control and Prevention (CDC) is a good source of information about bioterrorism. The following are the CDC's latest guidelines for handling suspicious mail:
[0013] Do not shake the suspicious package or envelope.
[0014] Do not sniff, touch or taste any contents that may have spilled out.
[0015] Do not carry the suspicious mail around and do not have others take a look at it.
[0016] Put the suspicious package or envelope on the floor or someplace where it will not fall over.
[0017] Leave the area, closing doors behind you. Tell others about the suspicious mail and keep anybody else from going into the area.
[0018] Wash your hands with plenty of soap and warm water.
[0019] If you are at work, report the incident to your supervisor, a security officer or police. If at home, call the police or sheriff's department.
[0020] Make a list of the people who were in the room when the package or letter was opened. Include all people who may have handled this mail. Give copies of the list to the police and to local public-health officials.
[0021] Further, the CDC indicates that mail is suspicious if;
[0022] Was sent by someone you do not know;
[0023] Is addressed to someone no longer at your address;
[0024] Has a hand-written address with no return address or with a return address that can not be confirmed as legitimate;
[0025] Is lopsided or lumpy;
[0026] Is sealed with excessive amounts of tape;
[0027] Is marked “PERSONAL” or “CONFIDENTIAL”; and
[0028] Has excessive postage.
[0029] Microbiologist report that micro waving the mail will not kill anthrax since microwaves work by heating water and spores have no water in them. A common clothing iron can reach sufficient temperatures to kill spores but would have to be applied for a length of time that is more likely to burn the mail than kill the spores. Also, the spores can spray out and become airborne if steam builds up inside the envelope. As a drastic measure, suspicious mail may be incinerated to kill anthrax at the obvious loss of the mail.
[0030] Unfortunately, current methods to control exposure to infectious bacteria do not provide the means for the individual mail recipient to eliminate infectious agents prior to handling the mail. Some people have responded to the threat of bioterrorism by stockpiling food, antibiotics and other goods but many people in metropolitan areas would likely have been already exposed. Some scientists say it's a giant leap from irradiating poultry or surgical instruments to decontaminating the millions of letters and packages the U.S. Postal Service delivers daily. Exposing mail to enough radiation might be slow and the energy needed to produce the radiation, possibly radioactive isotopes or devices to accelerate electrons, would be expensive. Scientist believe the procedure would not leave the mail radioactive but could cause damage to some of the contents, particularly food. There is also a danger from ozone exposure for those operating the machines. In some applications, chemicals would prove to be a more inexpensive and practical method to destroy infectious agents.
[0031] In these respects, the inventive solution departs from the conventional concepts and designs of the prior art, and in so doing provides a method primarily developed for the purpose to inexpensively and chemically eliminate infectious agents prior to mail handling by the postal facility and/or mail recipient.
SUMMARY OF THE INVENTION
[0032] In view of the foregoing disadvantages inherent in the known procedures to handle and eradicate infectious agents, the present invention provides a method and apparatus to eliminate biological agents before the mail comes in contact with the postal facility worker and/or mail recipient.
[0033] To attain this, the present invention comprises a bio-safe device that delivers a timed application of a decontaminant in an enclosed structure, or mailbox, to destroy biological agents on contaminated mail. In the first embodiment of the invention, the bio-safe device is configured to be readily installed in the common residential mailbox. In a second embodiment of the invention, the bio-safe device is installed in the U.S. Post Office mailbox. In a third embodiment of the invention, the bio-safe device is installed in the mail sorting center.
[0034] The bio-safe device is entirely managed by the owner. The bio-safe device is chemically charged and functionally checked on a periodic basis for operability. The bio-safe device is configured to discharge the decontaminant on a daily basis for a set duration of time to effectively eliminate the biological agent after each (daily) mail delivery. Consequently, the recipient and mail carrier is made aware of the eradication process through indication of the bio-safe device activity status clearly indicated on the mailbox to facilitate safe and complete operation.
[0035] It is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description. The invention is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood the phraseology and terminology employed herein are for the purpose of the description and should not be regarded as limiting.
[0036] A primary object of the present invention is to provide a method and apparatus to protect the general public against exposure to infectious agents on contaminated mail.
[0037] An object is to provide the method and apparatus for the individual mail recipient to destroy infectious agents before physical contact with the mail.
[0038] Another object is to provide a method and apparatus for the postal carrier or individual mail recipient to destroy infectious agents without destroying the mail.
[0039] Another object is to provide a method and apparatus for the postal carrier or individual mail recipient to inexpensively self manage the destruction of infectious agents.
[0040] Other objects and advantages of the present invention will become obvious to the reader and it is intended that these objects and advantages be within the scope of the present invention.
[0041] To the accomplishment of the above and related objects, this invention may be embodied in the form illustrated in the accompanying drawings, attention being called to the fact, however, that the drawings are illustrative only, and that changes may be made in the specific construction illustrated and described within the scope of the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0042] Various other objects, features and attendant advantages of the present invention will become fully appreciated as the same becomes better understood when considered in conjunction with the accompanying drawings, in which like reference characters designate the same or similar parts throughout the several views, and wherein:
[0043] [0043]FIG. 1 shows a block diagram of the functional elements of the bio-safe device.
[0044] [0044]FIG. 2 shows the application of the first embodiment of the bio-safe device.
[0045] [0045]FIG. 3 shows a detailed configuration of the first embodiment of the bio-safe device.
[0046] [0046]FIG. 4 shows the detail of the user control elements of the first embodiment of the bio-safe device.
[0047] [0047]FIG. 5 shows an application of the second embodiment of the bio-safe device.
[0048] [0048]FIG. 6 shows an application of the third embodiment of the bio-safe device.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0049] [0049]FIG. 1 shows a block diagram of the functional elements of the bio-safe device. The bio-safe device is housed in an enclosed structure, such as a common outdoor residential mailbox of the first embodiment, to effect treatment of deposited mail. A processor based controller 101 is central to the operation of the device. The controller includes a LCD front panel and pushbuttons to accept and display user inputs to define the activation periods of the device and system status. The controller depends on power delivered by a battery 103 or an optional solar panel 102 or 110 VAC line 109 . For reliability, so as to not be dependable on local household power, the device preferably utilizes a rechargeable battery to source operation, recharged via the solar panel or line cord under regulatory control by the controller. The device uses a door switch 104 to signal the controller when the enclosed structure door is closed enabling normal operation. The door switch also functions to signal an audible alarm with immediate termination of an ongoing treatment cycle in the event the enclosed structure is opened. Indicator lights 105 , under control of the controller 101 are also provided to indicate the bio-safe device status. A circulation fan 108 is provided to move the air/decontaminant mixture about the enclosed structure during the treatment cycle. An exhaust fan dries the mail surfaces and any residual airborne decontaminant within the enclosure through an external vent. An agitator 111 is provided to agitate the mail to ensure the entire surface of each piece of mail is effectively exposed to the decontaminant during the treatment cycle. A pump 107 , to be triggered by the controller during the treatment cycle, is provided to drive a liquid based decontaminant 110 through multiple nozzles as a fine mist to cover the mail in the enclosure. FIG. 1 also depicts an electrically actuated valve 106 to alternatively control a decontaminant from a compressed cylinder of gas. The gas is released into the enclosed structure in the form of a fog to cover the mail. The valve, like the pump, is subject to timed activation by the controller.
[0050] The decontaminant is preferably Bleach in 0.55% liquid concentration since it is inexpensive, easily prepared with dilution in water and proven effective against bacterial and viral agents. Household bleach at 5% solution is diluted to 0.5% by mixing 1 part of bleach with 9 parts water. However, household bleach reduces in strength with time and would require to be replaced in the bio-safe device daily. A “stable” form of bleach solution, marketed as a hospital cleaner disinfectant, is readily available and recommended for this application to avoid daily decontaminant changes in the bio-safe device. A surface sprayed wet with this bleach concentration at room temperature will kill bacteria such as Staphylococcus aureus, Salmonella choleraesuis, Pseudomonas aeruginosa, Yersinia pestis (Bubonic Plague) and Clostridium botulinum (Botulism) in one minute. It will also kill TB (Mycobacterium tuberculosis, Hepatitis A, B and C, HIV (AIDS), Tularemia, Smallpox, fungus and other viruses in a few minutes. Labs have successfully used this concentration applied wet for several minutes at room temperature to small work areas (desks and benches) to kill anthrax.
[0051] Other commercially available decontaminants in liquid or aerosol form for use in the bio-safe device are equally effective to kill infectious agents. The decontaminant product previously discussed by Sandia was successfully used on all manner of objects and less caustic than bleach. It was found a computer keyboard worked perfectly after treatment. After about an hour, the Sandia product leaves behind a clear soapy-like film or residue that can be wiped off with towels or rinsed off with water.
[0052] In operation of the bio-safe device, the decontaminant is pulsed as a mist or aerosol fog into the enclosed structure such that the mail is completely covered for about 30 minutes to be followed by a 2 minute forced air exchange cycle to dry and discharge airborne decontaminant. Activation of the treatment cycle depends on the start and stop times programmed by the user. The cycle will delay or not start if the controller monitors that the enclosure door (door switch) is open. An activated treatment cycle is immediately terminated if the enclosure door is opened. Typically, the bio-safe device user chooses a daily activation period after the enclosed structure is loaded; the mail has been delivered and before the user removes the mail at some later convenient time. Appropriately colored indicator lights and/or the control panel readout provides a warning to a mail carrier, or anyone else intent to open the mailbox, that the treatment cycle is in process (or complete) to avoid possible exposure to any infectious agent or concentrated amounts of moving decontaminant.
[0053] [0053]FIG. 2 shows an application of the first embodiment 200 of the bio-safe device. The bio-safe device 203 is inserted into the shape of the common household mailbox 201 . Although a residential freestanding type mailbox is shown, the rectangular type generally attached to the front of a house or other designs are equally employed. To support the effectiveness of the application, the mailbox has been modified with clear (Plexiglas) sides and top 202 to allow the user to see whether or not there is mail in the box and to check the status of the bio-safe device (agitating mail or status indicator lights). The clear surface also allows sunlight to energize solar panels 204 . The back of the mailbox is adapted to house a small cross section of weighted slats 205 opposite the circulation/exhaust fan 206 to facilitate the discharge of airborne decontaminant at the end of the treatment cycle. The rotation direction of the circulation fan may be reversed to also function as the exhaust fan. The exhaust fan develops sufficient air pressure to open weighted slats to ventilate the enclosure. A door switch 207 is provided to signal the bio-safe device when the mailbox door (or lid) 208 is open or closed.
[0054] [0054]FIG. 3 shows a detailed configuration 300 of the first embodiment of the bio-safe device. The bio-safe device 301 controller control panel 302 is positioned for easy access and viewing. A cavity with liquid tight lid 303 is provided to act as a reservoir for a liquid decontaminant or aerosol canister. If the decontaminant is a liquid, the pump described for FIG. 1 would drive the nozzles 304 to create a fine mist. If an aerosol decontaminant is selected, the valve described for FIG. 1 would control the compressed decontaminant out through similar nozzles as for the liquid decontaminant. The bio-safe device also uses an agitator 305 to shift the mail to effectively expose all surfaces of the deposited mail to the decontaminant during the treatment cycle. The agitator can take many forms such as simple alternating step up bars as shown in FIG. 3 or an oscillating wire cradle. The simple mechanics to drive a reciprocating type agitator is well known in the art. A pushrod 306 is provided to mechanically transfer the open or closed position of the mailbox door (or lid) to an internal switch sensed by the controller. The pushrod may contain a longitudinal screw apparatus to adjust an overall length to correctly fit the mailbox for proper actuation of the switch. A circulation fan 307 is included to move the misted or fog decontaminant about the enclosure during the treatment cycle. The circulation fan direction may be electrically reversed to ventilate the enclosure at the end of the treatment cycle. The reversed fan, or another fan, would produce sufficient air pressure to open a vent in the mailbox as described for FIG. 2. Solar panels 308 are optionally included to augment an internal battery and positioned on the bio-safe device or enclosure to effectively capture sunlight passing through the mailbox clear wall.
[0055] [0055]FIG. 4 shows 400 the detail of the user control elements of the first embodiment of the bio-safe device 401 . A Liquid Crystal Display (LCD) 402 is provided to display user inputs through several pushbuttons 403 and display the programmed and current status of the bio-safe device. Several indicator lights 404 are also provided to also indicate various status states of the bio-safe device including a green indicator to indicate the system is ready and functional, a yellow indicator to indicate the device is engaged in a treatment cycle and a red indicator to indicate a low level of decontaminant. A water tight battery compartment 405 is placed for easy access by the user. Battery charge status may be indicated by an indicator light or on the LCD. The LCD screen and pushbuttons may alternatively be replaced with a pair of accessible variable resistant pots to set the daily start time and period for the treatment cycle where the indicator lights would provide sufficient bio-safe device operability status.
[0056] [0056]FIG. 5 shows an application 500 of the second embodiment of the bio-safe device. The bio-safe device is functionally the same as discussed for FIGS. 1 - 4 but physically adapted for the larger U.S. Post Office mailbox 501 . The bio-safe device can also be adapted to other postal service drop boxes. The bio-safe device 502 is mounted to the inside of a door 503 for protection when closed and for easy access when open. An optional solar panel is mounted on a southern exposed surface of the mailbox 504 , perhaps the door, to augment the battery. In this application, the mailbox manager would program the bio-safe device to perform a treatment cycle prior to the scheduled mail pick-up. Postal boxes generally include a mail door that blocks access to the interior of the box when open; consequently, this configuration will protect the postal box user if accessed during a treatment cycle.
[0057] [0057]FIG. 6 shows an application 600 of the third embodiment of the bio-safe device housed in a postal mail sorting facility receiving box 601 . This application is intended for use at the mail entry point of a mail handling facility. The bio-safe device discussed in FIGS. 1 - 4 is physically reconfigured 604 to decontaminate mail 602 in a large enclosure or small room. Mail is moved through the treatment enclosure on a speed controlled conveyor belt 603 with physical shifting of the mail to ensure sufficient coverage and coverage time by the decontaminant. The processing unit includes design advantages to facilitate the treatment cycle including barrier strip doors to minimize the egress of decontaminant, clear panels for process inspection and filtered exhaust vent to manage residual decontaminant. The bio-safe device and conveyor belt are necessarily programmed to serially treat large amounts of mail.
[0058] It will be appreciated that in general, the inventive product decontaminates cross contaminated mail. The inventive solution destroys biological agents prior to the mail carrier or individual mail recipient handling the mail thus eliminating exposure and a dependence on belated public warning notices or early disease detection.
[0059] While specific embodiments of the invention have been described and illustrated, such embodiments should be considered illustrative of the invention only and not as limiting the invention as construed in accordance with the accompanying claims. As to a further discussion of the manner of usage and operation of the present invention, the same should be apparent from the above description. Accordingly, no further discussion relating to the manner of usage and operation will be provided.
[0060] With respect to the above description then, it is to be realized that the optimum dimensional relationships for the parts of the invention, to include variations in size, materials, shape, form, function and manner of operation, assembly and use, are deemed to be within the expertise of those skilled in the art, and all equivalent structural variations and relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention.
[0061] Therefore, the foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.
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A method and apparatus is provided to protect the mail carrier and mail recipient from exposure to mail contaminated with biological agents. A bio-safe device is user programmed and loaded with an inexpensive decontaminant to automatically perform a treatment cycle on deposited mail to eliminate anthrax and other infectious agents from within an enclosed mail receptacle. This provides the delivery mail carrier or an individual mail recipient the means to destroy infectious agents before physical contact with the mail.
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CLAIM OF PRIORITY
This application claims priority under 35 USC § 120 to PCT/US01/07939, filed Mar. 12, 2001, which claims priority from U.S. Patent Application Ser. No. 60/189,136, filed on Mar. 14, 2000, the entire contents of both of which are hereby incorporated by reference.
TECHNICAL FIELD
This invention relates to stretchable fasteners and especially to stretchable fasteners that may be practical and cost efficient for fastening applications where elasticity and flexibility is desired.
BACKGROUND
Stretchable fasteners that carry hook and loop closures are desirable as part of infant and adult diapers, surgical gowns, and other garments and wraps. The fasteners typically comprise sheet, film or non-woven webs of elastic construction that have embossing or other surface patterns for grasping by the user. To the back of such an elastic web, a tape of fastener elements is secured, forming a laminate structure. The fastener tape is typically made of a synthetic resin that is not stretchable, and the resulting laminate is relatively stiff, does not stretch, and does not present the desired degree of cloth-like feel.
It is desirable that the substance of the tab and the associated fastener tape provide an integral, stretchy component that achieves the desired qualities, such as elasticity, flexibility and cloth-like feel.
SUMMARY
The invention features, in several of its aspects, a method of forming stretchable fasteners. The fasteners have a base of synthetic resin, and an array of loop-engageable fastener elements integrally molded with and extending from the base.
According to one aspect of the invention, a method of forming a stretchable fastener product includes providing a sheet-form fastener tape, processing the fastener tape including slitting to form longitudinally extending bands of fastener tape and to space said fastener bands transversely apart, and attaching the transversely spaced apart fastener bands to a sheet form elastic web.
In some cases, the elastic web extends across the fastener bands as well as across spaces between adjacent spaced apart bands and in other cases the elastic web extends only across spaces between adjacent spaced apart bands.
Transversely spaced apart bands are formed by passing the slit fastener tape bands through a separator that separates the bands and spaces them transversely apart, or by removing every other adjacent band of the slit fastener tape bands. The transversely spaced apart fastener bands are attached to the elastic web by thermal fusion, ultrasonic welding, or an adhesive. In one embodiment, the every other adjacent band that has been removed is attached to a second sheet form elastic web to form a second stretchable fastener.
Certain, exemplary embodiments of the invention have one or more of the following features. The fastener tape comprises a base of synthetic resin, and an array of loop-engageable fastener elements integrally molded with and extending from a first surface of the base. The array of loop-engageable fastener elements has a density of the order of 500 or more fastener elements per square inch. The array of loop-engageable fastener elements has a density of the order of 1000 or more fastener elements per square inch. The fastener elements have relatively stiff stems and hook-shaped heads and in some instances the stems have a greater cross-section than the hook-shaped heads. The fastener elements have relatively stiff stems and disc-shaped heads. The disc-shaped heads have a flat top surface.
In some embodiments, the transversely spaced apart fastener bands are attached to the elastic web by supporting the spaced apart fastener bands on a support roll, wherein the loop-engageable fastener elements are in contact with a surface of the support roll, while simultaneously pressing and heating the elastic web against a second surface of the base of the fastener tape bands. A heated laminating roll or a continuous belt is arranged to press the elastic web against the second surface of the base of the fastener bands to promote lamination.
The support roll may have circumferential recesses, which are configured to support the fastener bands and to position the second surface of the base of the fastener bands at the surface of the support roll.
In some cases, a backing is attached to the second surface of the base of the fastener bands. The backing may be a heat-sensitive adhesive, and the method then includes the step of activating the adhesive before engagement with the elastic web.
According to another aspect of the invention, a stretchable fastener product is formed by first introducing a moldable first material to a continuously rotating mold roll to form a sheet-form fastener having a base conforming to a surface of the mold roll and multiple rows of molded fastener elements integral with the base. The rows extend in a longitudinal direction of the sheet-form fastener and the fastener elements are formed by mold cavities of the mold roll. The thus-formed sheet-form fastener is then slit into longitudinally extending band portions carrying multiple rows of the fastener elements. Spaces are then created between adjacent bands transverse to the longitudinal direction, and subsequently a web of a second material different from the material of the fastener elements is joined to the transversely spaced apart bands.
Exemplary embodiments may have one or more of the following features. The second material is resiliently extensible. The slit bands of the fastener product are removed from the mold roll, and are passed through a separating device that develops space between the adjacent bands transversely to the longitudinal direction. Thereafter the bands are introduced onto a surface of a support roll, and the web of the second material is joined to the bands by pressure and heat while the fastener bands are on the support roll. The support roll may have circumferential recesses, which are configured to support the fastener bands and to position the second surface of the base of the fastener bands at the surface of the support roll.
In some embodiments the fastener elements are loop-engageable hooks molded of synthetic resin of density of the order of 1000 or more fastener elements per square inch. The fastener elements may have relatively stiff stems of greater cross-section than their loop-engageable hooks. The hooks of the fastener elements of a given band may engage the bottom of the respective recess and may be collectively self supporting under the pressure of laminating, serving to assist in producing laminating pressure by which the bands are joined to the second material. A heated laminating roll or a continuous belt is arranged to press the second material against the second surface of the fastener bands to promote lamination.
In some embodiments a sheet-form fastener is formed on the mold roll having bands of fastener elements spaced apart from bands of material to be removed. The sheet-form fastener is then slit and the bands of material to be removed are removed while the bands of fastener elements remain on the mold roll. While the fastener elements thus continue to reside in their respective mold cavities, and with the mold roll serving as a pressure roll, a second material is joined to the bands. The second material is a molten resin introduced to the mold roll into contact with regions vacated by the bands of material that have been removed. Portions of the mold roll corresponding to the spaces between the bands of fastener elements may be substantially smooth cylindrical sections. In some cases the second material is introduced across the width of the bands of fastener elements as well as the vacated spaces between the bands of fastener elements.
In some embodiments, a second parallel roll forms a nip with the mold roll, and an extruder is arranged to deliver molten resin to the nip to serve as the second material, the nip being effective to apply the resin as a layer that bridges between the bands of fastener material.
The fastener elements are loop engageable hooks molded of resin selected from the group consisting of polyester, polyethylene, polypropylene, polyamide and copolymers and alloys thereof. The second material is comprised of a resilient resin having an elongation in the range of 50% to 300% and a recovery of at least 75%. The second material is selected from the group consisting of thermoplastic elastomers, thermoplastic polyurethanes, elastomeric copolymers containing polyethylene terephthalate (PET), thermoplastic olefins, and natural or synthetic rubber. The second material may also be a preformed nonwoven loop material, the loop material being releasably engageable by the fastener tape. The nonwoven material may be a needled web having a basis weight of less than about 4 oz/square yard.
In some embodiments, each of the fastener bands and spaces between the fastener bands has a width of ¼ inch (6.4 mm) or less. In other embodiments each of the fastener bands and spaces between the fastener bands has a width greater than ¼ inch (6.4 mm). In other embodiments, each of the fastener bands has a width less than or equal to ¼ inch ( 6/4 mm), and each of the spaces between the fastener bands has a width greater than or equal to ¼ inch (6.4 mm). In yet other embodiments, each of the fastener bands has a width greater than or equal to ¼ inch ( 6/4 mm), and each of the spaces between the fastener bands has a width less than or equal to ¼ inch (6.4 mm).
According to another aspect of the invention, a method of forming a stretchable fastener product is disclosed, the method including introducing a moldable first material to a continuously rotating mold roll to form a sheet-form product having a base conforming to a surface of the mold roll and multiple rows of stem elements integral with the base, the rows extending in a longitudinal direction of the sheet-form fastener, the stems formed by mold cavities of the mold roll. The method also includes heating a tip portion of the stems, contacting a cooled roller to the tip portion of the stems to produce disc-shaped engaging heads on the stems, slitting the thus-formed sheet-form fastener into longitudinally extending band portions carrying multiple rows of the fastener elements, creating space between adjacent bands transverse to the longitudinal direction, and subsequently joining to the transversely spaced apart bands a web of a second material different from the material of the fastener elements.
An exemplary embodiment of this aspect of the invention may include creating space between adjacent bands by directing selected bands to a first station and directing bands adjacent the selected bands to a second station, whereby the selected bands form a first set of transversely spaced apart bands and the bands adjacent the selected bands form a second set of transversely spaced apart bands, each of the first and second stations being provided for performing the joining operation, whereby the first set is laminated to a first web of the second material to form a first stretchable fastener product and the second set is joined to a second web of the second material to form a second stretchable fastener product. Other variations of this aspect of the invention can include any of the features described above with reference to other aspects of the invention.
Another aspect of the invention is a method of simultaneously forming multiple stretchable fastener products including providing a sheet-form fastener tape, slitting the sheet-form fastener tape to form longitudinally extending bands of fastener tape, directing a first set of the bands to a first attachment station and directing a second set of the bands to a second attachment station, the bands of the first and second sets being selected so that each set comprises transversely spaced apart fastener bands, and attaching the first set of transversely spaced apart fastener bands to a sheet form elastic web at the first attachment station and attaching the second set of transversely spaced apart fastener bands to a sheet form elastic web at the second station to simultaneously form multiple stretchable fastener products.
Variations of this aspect of the invention can include any of the features described above with reference to other aspects of the invention.
According to another aspect of the invention, a stretchable fastener product is provided by employing one of the above-described methods. The stretchable fastener has an elastic web, and multiple fastener tape bands attached to the elastic web and configured to be oriented parallel to each other and spaced apart from each other.
Variations of this aspect of the invention can include any of the features described above with reference to other aspects of the invention.
In some embodiments, each fastener band comprises a base of synthetic resin, and an array of loop-engageable fastener elements integrally molded with and extending from a first surface of the base. The array of loop-engageable fastener elements may have a density of the order of 1000 or more fastener elements per square inch. The fastener elements may have relatively stiff stems and hook-shaped heads, and the stems may have greater cross-section than the hook-shaped heads. A backing may be attached to a second surface of the base, and the backing may be a heat-sensitive adhesive. The resin may be selected from the group consisting of polyester, polyethylene, polypropylene, polyamide and copolymers and alloys thereof. The elastic web may be made of a resilient resin and may have an elongation in the range of 50% to 300% and a recovery of at least 75%. The elastic web may be selected from the group consisting of thermoplastic elastomers, thermoplastic polyurethanes, elastomeric copolymers containing PET, thermoplastic olefins, and natural or synthetic rubber.
The elastic web may be a preformed nonwoven loop material, and the nonwoven material may be a needled web having a basis weight of less than about 4 oz/square yard.
The fastener bands and spaces between the fastener bands may each be of the order of ¼ inch or less wide and ¼ inch or less wide, respectively.
According to another aspect of the invention, a stretchable fastener product includes multiple fastener tape bands and multiple elastic web bands, and edge margins of the elastic web bands are attached to edge margins of the fastener bands. The edge margins of the elastic web bands may overlap or abut the edge margins of the fastener bands.
Among the advantages of the invention may be one or more of the following. The stretchable fasteners of this invention do not “set”, i.e., stretch partially irreversibly, have hooks with strong structural integrity and are cost efficient.
Other features and advantages of the invention will be apparent from the following description of embodiments, and from the claims.
The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.
DESCRIPTION OF DRAWINGS
FIG. 1 is a perspective view of a stretchable fastener having spaced apart bands of fastener tape attached onto an elastic substrate.
FIG. 1A is an expanded side view of the stretchable fastener of FIG. 1 .
FIG. 1B is an expanded side view of the stretchable fastener of FIG. 1A taken in plane 1 B- 1 B.
FIG. 1C is an expanded top view of the fastener of FIG. 1 .
FIG. 1D is an expanded side view of another embodiment of a stretchable fastener.
FIG. 2 is an expanded side view of another embodiment of a stretchable fastener having spaced apart bands of fastener tape attached onto an elastic substrate.
FIG. 2A is an expanded top view of the fastener of FIG. 2 .
FIG. 3 illustrates a method and an apparatus for forming the stretchable fastener of FIG. 1 .
FIG. 3A is an expanded perspective view of the channeled roll 230 in FIG. 3 .
FIG. 3B is a side view of a channeled roll taken in plane 3 B- 3 B of FIG. 3 .
FIG. 3C is a cross sectional view of a stretchable fastener taken in plane 3 C- 3 C of FIG. 3 .
FIG. 3D illustrates a variation of the method and apparatus of FIG. 3 .
FIG. 4 is a perspective view of a separator that spreads apart the incoming slit fastener bands.
FIGS. 4A is a cross sectional view of a separator taken in plane 4 A- 4 A of FIG. 4 .
FIG. 4B is a perspective view of a separator that creates spaces between the adjacent slit fastener bands by removing every other band of the incoming slit bands.
FIG. 4C is a cross sectional view of the separator in FIG. 4B taken in plane 4 C- 4 C in FIG. 4 .
FIG. 5 illustrates another method and another apparatus for forming the stretchable fastener of FIG. 1 .
FIG. 5A is an expanded view of area 5 A in FIG. 5 .
FIG. 5B is a cross sectional view of the apparatus in FIG. 5 taken in plane 5 B- 5 B.
FIG. 6A is a side view of the fastener tape 70 in FIG. 5 .
FIG. 6B is a side view of the slit fastener bands 80 in FIG. 5 .
FIG. 6C is a side view of the stretchable fastener 100 in FIG. 5 .
FIG. 7 illustrates another method and an apparatus for forming the stretchable fastener of FIG. 1 .
FIG. 7A is an expanded view of area 7 A in FIG. 7 .
FIG. 7B is a side view of the fastener tape 70 in FIG. 7 .
FIG. 7C is a cross sectional view of the apparatus in FIG. 7 taken in plane 7 C- 7 C.
FIG. 8 is a cross sectional view of a slotted die having multiple slot openings.
FIG. 9 illustrates another method and an apparatus for forming the stretchable fastener of FIG. 9B .
FIG. 9A is a side view of the molded fastener bands 80 in FIG. 9 .
FIG. 9B is a side view of a stretchable fastener having spaced apart fastener bands attached to elastic bands.
FIG. 9C is a side view of another embodiment of a stretchable fastener having spaced apart fastener bands attached to elastic bands.
FIG. 10 illustrates another method and an apparatus for forming the stretchable fastener of FIGS. 9B and 9C .
FIG. 10A is a cross sectional view of the two separated slotted dies 41 and 51 of FIG. 10 taken along plane 10 A- 10 A.
FIG. 10B is an expanded view of the nip area 44 in FIG. 10 .
FIG. 11 is a top view of a stretchy diaper tab.
FIG. 11A illustrates a diaper with a stretchy diaper tab.
FIG. 12 is a side view of an alternative fastener element that can be used for the stretchable fastener of FIG. 1 .
FIG. 13 is a diagrammatic illustration of a method and apparatus for making a stretchable fastener similar to that of FIG. 1 , but having fastener elements similar to that of FIG. 12 .
Like reference symbols in the various drawings indicate like elements.
DETAILED DESCRIPTION
Referring to FIGS. 1 and 1A , a stretchable fastener 100 features spaced apart bands of fastener tape 104 , attached to a sheet-form elastic substrate 102 . Each fastener band 104 has a width w 1 of the order of ⅛ inch and is spaced apart from a neighboring fastener band by a distance w 2 of the order of ⅛ inch. Each fastener band has rows 105 of fastener elements 106 integral with a base layer 108 ( FIG. 1A ). During use of the stretchable fastener a stress is applied along a stretching direction 112 . The applied stress causes an elongation of the elastic layer 102 parallel to the stretching direction, and when the stress is removed the fastener 100 returns to its original dimensions. In this embodiment, the fastener elements are in the form of J-hooks and extend in rows 105 perpendicular to the stretching direction 112 . The J-hooks have a stiff stem 114 and a hook shaped head 116 ( FIG. 1B ) pointing in the direction of the arrows ( FIG. 1C ) and perpendicular to the stretching direction 112 . Adjacent rows of hooks 105 have oppositely oriented hooks 106 , as shown in FIG. 1C . The cross-sectional diameter of the stem d 1 is greater than the cross-sectional diameter of the hook shaped head d 2 .
In one example, the hooks are of CFM-29 designation, available from Velcro USA Inc. of Manchester, N.H., U.S.A. The CFM-29 hook strip has hooks of only 0.015 inch (0.38 mm) height h, a base thickness t 1 of 0.003 inch (0.08 mm) and a fastener element density of the order of 1000 or more fastener elements per square inch. The thickness t 2 of the elastic substrate is 0.005 inch (0.13 mm) ( FIG. 1B ).
The elastic layer 102 is composed of a thermoplastic elastomer, such as Santoprene , having an elongation in the range of 50% to 300% and a recovery of at least 75%. The fastener bands 104 are composed of a synthetic resin such as, polypropylene, polyethylene terephthalate (PET), polyethylene, nylon and polyvinyl chloride (PVC), among others. The fastener bands are attached to the elastic layer by thermal fusion generated by ultrasonic or thermal welding.
In the embodiment of FIG. 1D , the fastener bands 104 have a backing layer 110 attached to a surface of the base layer 108 opposite the surface with the fastener elements 106 . The backing layer 110 is composed of a resin that facilitates the fusion between the base layer 108 and the elastic layer 102 . In some instances, the backing layer 110 is an adhesive that bonds the base layer 108 to the elastic layer 102 .
Referring to FIGS. 2 and 2A , a stretchable fastener 100 features spaced apart bands of fastener tape 104 , attached to a sheet-form elastic substrate 102 . Each fastener band has rows 105 of fastener elements 106 integral with a base layer 108 ( FIG. 2A ). The fastener elements 106 are in the form of J-hooks and extend in rows 105 perpendicular to the stretching direction 112 . The J-hooks have a stem 114 and a hook shaped head 116 ( FIG. 1B ) pointing in the direction of the arrows ( FIG. 1C ) and parallel to the stretching direction 112 .
Referring to FIGS. 9B and 9C , a stretchable fastener 100 features spaced apart fastener tape bands 80 , joined together by bands of an elastic substrate 88 . The elastic substrate bands 88 have edge margins 89 overlapping ( FIG. 9B ) or abutting ( FIG. 9C ) edge margins 87 of the fastener bands 80 . Each fastener band 80 has rows 72 of fastener elements 106 integral with a base layer 108 ( FIG. 2A ). The fastener elements 106 are in the form of J-hooks and extend in rows 72 perpendicular to the stretching direction 112 .
The products of FIGS. 1 and 2 may be economically formed by the process and apparatus illustrated in FIG. 3 . A sheet-form fastener 200 , supplied by roll 208 , is slit by slitter 210 to form fastener tape bands 202 extending in a longitudinal direction. The slit fastener bands 202 subsequently pass through a separator 221 . Separator 221 , separates the slit fastener bands 202 and spaces them apart transverse to a machine direction 60 . The spaced apart fastener bands are then introduced into spaced apart channels 232 formed on the surface of the channeled roll 230 ( FIGS. 3A and 3B ). The hook-shaped fastener elements 106 have relatively stiff stems with greater cross-section than the loop-engageable hooks and reside in the channels 232 . The hooks of the fastener elements of a given band engage the bottom of the respective channel 232 . The channels 232 have a width equal to the fastener band width w 1 and are spaced apart by a distance equal to the fastener band spacing w 2 . The fastener bands travel around a segment of the periphery of the channeled roll 230 and are introduced into a nip 242 , formed between the channeled roll 230 and a heated pressure roll 250 . Simultaneously with the fastener bands, a sheet-form elastic web 240 is introduced into the nip 242 . The heated roll presses and fuses the elastic web 240 onto the back surface of the fastener bands 202 . The hooks engaging the bottom of the channels 232 are collectively self-supporting under the pressure of laminating and assist in producing the laminating pressure by which the bands are joined to the second material. The composite elastic web with the attached fastener bands 100 is then removed from the heated roll 250 .
As illustrated in FIG. 3D , the method and apparatus described above with reference to FIG. 3 can be modified to remove separator 221 . Sheet-form fastener 200 , after being slit by slitter 210 to form fastener tape bands 202 passes through tensioning nip rolls 211 and 212 where selected tape bands 202 ′ are directed to channeled roll 220 while tape bands 202 ″ adjacent to selected tape bands 202 ′ are directed to another channeled roll 220 ′. The processing of each set of tape bands 202 ′, 202 ″ then proceeds in a similar manner to that described above, except the two sets of tape bands 202 ′, 202 ″ are processed in parallel. Accordingly, elastic film is provided by two respective film stretchers 244 , 244 ′ and lamination is carried out by two respective heated rolls 250 , 250 ′ that form respective nips 242 , 242 ′ with channeled rolls 220 , 220 ′. The parallel processing yields two completed elastic fastener products 100 , 100 ′.
While the example illustrated in FIG. 3D illustrates simultaneous production of two elastic fastener products, similar arrangements with three or more sets of apparatus for parallel processing of a corresponding sets of spaced bands can also be achieved.
Referring to FIGS. 4 and 4A , the separator 221 has spaced apart openings 222 and is configured to receive the adjacent slit fastener bands 1 to 5 and place each one in a separate opening. There are at least as many openings as the number of slit fastener bands and each opening has a width at least equal to the fastener band width w 1 . The spacing w 2 between openings 222 corresponds to the desired spacing of the fastener bands 202 in the stretchable fastener 100 . By passing though the spaced apart openings, fastener bands 1 to 5 are separated and exit the separator 221 spaced apart at a distance w 2 .
In the embodiment shown in FIGS. 4B and 4C , the separator 221 is configured to separate incoming slit bands 1 to 5 by removing every other band, i.e., bands 2 and 4 are removed and bands 1 , 3 and 5 exit the separator spaced apart by a distance w 2 corresponding to the width of the removed bands. Bands 2 and 4 are introduced into openings 224 , formed in the separator 221 . Openings 224 are oriented perpendicular to the machine direction and direct bands 2 and 4 toward the recycling bin. Alternatively, the two sets of spaced apart bands, i.e., a first set formed by bands 1 , 3 , and 5 and a second set formed by bands 2 and 4 , are each directed to a laminating apparatus and two fastener products are simultaneously produced, as discussed above with reference to FIG. 3D .
The stretchable fastener of FIG. 1 may also be formed by the process and apparatus illustrated in FIG. 5 .
Extruder barrel 42 melts and forces molten plastic 40 through a slot-form die 41 . The extruded plastic enters nip 44 formed between base roll 48 and mold roll 46 . Mold roll 46 contains cavities 45 shaped to form hook-type fastener elements. The hook cavities 45 ( FIG. 5A ) are arranged in separated bands 50 on the surface of the mold roll 46 ( FIG. 5B ). Smooth bands 51 that contain no cavities separate the hook cavity bands 50 . The width of the cavity bands 50 equals the width of the fastener tape bands w 1 and the width of the smooth bands 51 equals the desired spacing between the fastener tape bands w 2 . The sheet-form fastener material 70 ( FIG. 6A ) formed in nip 44 has rows of hook fastener elements integrally molded with a base layer alternating with rows of only the base layer. The fastener material 70 travels about a segment of the periphery of mold roll 46 to slitting roll 210 . Slitting roll 210 slits and removes the bands of only the base layer 76 thus forming spaced apart bands of fastener tape 80 ( FIG. 6B ) having fastener elements residing in the hook molds of the mold roll 46 . A second extruder 52 introduces molten plastic 49 , suitable for molding an elastic web, through a slot-form die 53 into a nip 54 formed diametrically opposite nip 44 between the mold roll 46 and a third roll 55 . Molten plastic 49 is squeezed down to a thin film 102 and is applied to the back surface 84 of the fastener bands 80 on the mold roll 46 and fills the empty spaces 82 between the fastener bands. The back surfaces of the spaced apart fastener bands 82 fuse together with the continuous thin film 102 by the heat and pressure generated between the mold roll 46 and third roll 55 . The formed composite elastic web with the attached fastener bands 100 ( FIG. 6C ) is subsequently removed from the third roll 55 .
For more detail about the general operation of the in situ molding apparatus of FIG. 5 , the reader is referred to U.S. Pat. No. 5,260,015 to Kennedy, et al., which discloses laminates made with loop materials.
The stretchable fastener of FIG. 1 may also be formed by the embodiment illustrated in FIG. 7 . Extruder barrel 42 melts and forces molten plastic 40 through a slot-form die 41 . The extruded plastic enters the nip 44 between base roll 48 and mold roll 46 . The entire outside surface of the mold roll 46 contains cavities 45 shaped to form hook-type fastener elements. The sheet-form fastener material 70 ( FIG. 7B ) formed in nip 44 has rows of hook fastener elements 106 integrally molded with a base layer 74 . The fastener material 70 travels about the periphery of mold roll 46 and is guided by two guide rolls 56 and 58 to slitting rolls 210 . Slitting rolls 210 slit the fastener 70 into bands 80 which are then separated by passing through separator 221 . The spaced apart fastener bands 80 are then introduced into spaced apart channels 232 formed on the surface of the channeled roll 230 ( FIG. 7C ). The hook-shaped fastener elements 106 reside in the channels 232 with the hooks engaging the bottom of the respective channel. The channels 232 have a width equal to the fastener band width w 1 and are spaced apart by a distance equal to the fastener band spacing w 2 . The fastener bands are introduced into a nip 242 , formed between the channeled roll 230 and a heated pressure roll 250 . Simultaneously with the fastener bands, a sheet-form elastic web 240 is introduced into the nip 242 . The heated roll 250 presses and fuses the elastic web 240 onto the back surface 84 of the fastener bands 80 . The hooks engaging the bottom of the channels 232 are collectively self supporting under the pressure of laminating and assist in producing the laminating pressure by which the bands are joined to the second material. The composite elastic web with the attached fastener bands 100 is then removed from the heated roll 250 .
In the embodiment of FIG. 9 , separated fastener bands 80 are formed directly on the mold roll 46 by using a slot form die 41 that has multiple spaced apart slots 43 ( FIG. 8 ). Mold roll 46 contains cavities 45 shaped to form hook-type fastener elements, and the hook cavities 45 ( FIG. 5A ) are arranged in separated bands 50 on the surface of the mold roll 46 ( FIG. 5B ). Slots 43 are aligned to inject molten resin into the cavity bands 50 of the mold roll 46 , have a width equal to the fastener band width w 1 , and are spaced apart by a distance equal to the spacing between the fastener tape bands w 2 . A second slotted die 53 with multiple slots is used in the second extruder 52 to form bands of elastic film 88 filling the spaces 82 between the fastener tape bands 80 ( FIG. 9B ). The edge margins 89 of the bands of elastic film 88 overlap the edge margins 87 of the fastener bands 80 . In some embodiments ( FIG. 9C ), the edge margins 89 of the bands of elastic film 88 abut the edge margins 87 of the fastener bands 80 .
In the embodiment of FIG. 10 , the bands of elastic film 88 are coextruded with the bands of the fastener tape 80 by using an extruder with separate chambers 42 and 52 and two separate slotted dies 41 and 53 connected to the separate chambers 42 and 52 , respectively ( FIG. 10B ). The two slotted dies 41 and 53 have multiple slot openings 41 a to 41 d and 53 a to 53 c , respectively ( FIG. 10A ). Two different types of molten resin are simultaneously extruded into the same nip 44 . The coextruded bands of fastener tape 80 and elastic film 88 are fused at the margins 89 and 87 by the pressure and heat provided by roll 48 .
Other features and advantages of this invention may include one or more of the following. A continuous heated belt may be used to apply pressure and heat to the elastic web to cause fusion to the back surface of the fastener bands. Elastic webs having an elongation of at least 300% and recovery of at least 75% may be used. The width of the fastener bands may be between ⅛ to ¼ inch (3.18 to 6.35 mm). The width of the elastic bands may be between ⅛ to ¼ inch (3.18 to 6.35 mm). Narrow fastener bands separated by narrow elastic bands are used to form stretchable fasteners covering a large area. Large area stretchable fasteners may be used to form stretchable bands that provide motion flexibility. A wide stretchable fastener band 18 next to a wide elastic band 19 may be used to form a fastener tab 12 used as part of infant and adult diapers 10 ( FIGS. 11 and 11A ).
Although each of the above-described examples has referred to hook-shaped fastener elements, any shape suitable for engaging a loop or mesh material, or capable of engaging other fastener elements of like or unlike shape is suitable. For example, U.S. Pat. No. 6,248,276, the full contents of which are hereby incorporated by reference, discloses various suitable fastener elements and methods and apparatus for their manufacture. Briefly, referring to FIG. 12 , one example of an alternative fastener shape is fastener element 10 which includes a base 12 and a fastener element 14 extending from the base. (Fastener 10 generally includes an array of fastener elements; a single fastener element is shown for clarity.) Fastener element 14 includes a stem 16 and, at the terminal end of stem 16 , a head 18 . Head 18 is shaped for engagement with another fastener component, for example a female fastener component having a plurality of loops, a mesh such as an insect screen, or another fastener component similar to fastener 10 .
As shown in FIG. 12 , head 18 is substantially disc-shaped, including a substantially planar top surface 20 , and a substantially planar bottom surface 22 that faces and overhangs base 12 . It is desirable that the disc be relatively thin, allowing a cooperating fastener element, e.g., a loop or the wire mesh of a window screen, to penetrate into the disc by flexing the disc material. Preferably, the thickness of the disc is from about 5 to 15% of the equivalent diameter of the disc. If the disc is thinner, it will tend to have reduced cycle life (i.e., durability during repeated engagement and disengagement of the fastener), whereas if the disc is thicker the fastener may exhibit reduced peel strength.
A machine 300 for forming the fastener elements 10 described above is shown in FIG. 13 . For a more detailed description the reader is again referred to previously incorporated U.S. Pat. No. 6,248,276. Briefly, a supply roll 302 introduces a continuous supply of a stem-carrying base 12 ( FIG. 12 ) into the machine 300 . Stem-carrying base 12 is formed of a thermoformable polymer. In a previous manufacturing step, roll 302 was wound up as the take-up roll at a molding station (not shown, but one example of a stem molding method is similar to the hook molding operation described above with reference to FIGS. 5 and 7 wherein the mold cavities have a straight stem shape instead of a hook shape) at which stems were integrally molded onto base 12 . Alternatively, as discussed further below, the stem-carrying base 12 has already been slit, separated and joined to an elastic web using, e.g., one of the methods and apparatus previously described with reference to FIGS. 3 , 3 D, 5 , 7 or 9 .
The supply roll 302 is unwound by drive mechanism 306 , which conveys stem-carrying base 12 into optional pre-heating area 308 which raises the temperature of the stem-carrying base 12 to a pre-heat temperature that is above room temperature but much lower than the temperature at which the polymer melts or deforms. This pre-heating allows the tips of the stems to be heated to a predetermined softening temperature more quickly during the next step of the process.
Next, the base 12 moves to heating device 310 , which heats only a distal portion, i.e., a portion furthest from base 12 , of the stems. The remainder of the stem remains relatively cool and thus relatively rigid. The distal portion is heated to a softening temperature at which it can be formed into a desired head shape. To ensure that only the distal portion of each stem is heated to the softening temperature, it is preferred that heating device 310 include a non-contact heat source that is capable of quickly elevating the temperature of material that is very close to the heat source, without raising the temperature of material that is relatively further away from the heat source. Suitable non-contact heat sources include flame heaters, electrically heated nichrome wire, and radiant heater blocks. To heat the distal portion to the softening temperature without contact, the heat source typically must be at a relatively high temperature. For example, if the softening temperature is from about 100 to 140° C., the temperature of the heat source will generally be from about 300 to 1000° C. and the heat source will be positioned from about 0.1 to 30 mm from the tips of the stems.
After the distal portions of the stems have been heated, the base 12 moves to conformation head 312 , at which base 12 passes between conformation roll 314 and drive roll 316 . Conformation roll 314 forms the distal portion of the stems into a desired head shape, as will be described in further detail below, while drive roll 316 advances base 12 and flattens it against roll 314 to enhance head uniformity. It is preferred that the temperature of conformation roll 314 (the forming temperature) be lower than the softening temperature. Maintaining the conformation roll 314 at this relatively low temperature has been found to allow the conformation roll to flatten the spherical (“ball-shaped”) heads that are generally formed during the previous heating step into a desired head shape. Spherical heads are generally undesirable, as such heads tend not to provide secure engagement with a mating fastener. A low forming temperature also prevents adhesion of the thermoformable polymer to the conformation roll. Generally, to obtain the desired forming temperature it is necessary to chill the conformation roll, e.g., by running cold water through a channel in the center of the roll, to counteract heating of the conformation roll by the heat from the distal portions of the stems. If further cooling is needed to obtain the desired forming temperature, the drive roll may be chilled in a similar manner.
The surface texture of conformation roll 314 will determine the shape of the heads that are formed. If disc-shaped heads having a smooth surface (as illustrated in FIG. 12 ) are desired, the surface texture will be smooth and flat. If a sandpaper-like surface is desired, the surface texture of the conformation roll will be sandpaper-like. If mushroom-shaped (domed) heads are desired, the conformation roll will include a plurality of substantially hemispherical indentations (“dimples”) to form the dome portion of the heads. Other shapes are of course possible by using a conformation roll with a surface shape corresponding to the desired fastener head shape.
The spacing of the conformation roll 314 from the drive roll 316 is selected to deform distal portions of the stems to form the desired head shape, without excessive damage to the unheated portion of the stems. It is also preferred that the spacing be sufficiently small so that the drive roll flattens base 12 and provides substantially uniform contact pressure of the stem tips against the conformation roll. Preferably, the spacing is approximately equal to the total height of the stem less the length of the heated distal portion.
Next, the base 12 moves to a cooling station 318 . Cooling station 318 cools the formed heads, e.g., by cool air, preventing further deformation of the heads. Preferably, the heads are cooled to approximately room temperature. The cooled base is then moved through driving station 320 and is then passed through a slitter 322 , a separator 324 , and a joining station 326 where separated bands of the product are joined to an elastic web. Slitter 322 , separator 324 , and joining station 326 , can be apparatus similar to those described above, e.g., with reference to FIGS. 3 or 3 D, and operate in a similar manner.
In an alternative arrangement, a base having stems only, is formed, slit and joined to a stretchable web as described above with reference to FIGS. 3 , 3 D, 5 , 7 , and 9 , and the stems are later formed into a fastener shape as described above with reference to FIGS. 12 and 13 . The resulting fastener product 100 ′ is similar to that shown, e.g., in FIGS. 1-1D but having fastener elements similar to that illustrated in FIG. 12 .
A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.
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Stretchable fastener products are formed by providing a sheet-form fastener tape, slitting the fastener tape to form longitudinally extending bands of fastener tape and separating the longitudinally extending bands to space the fastener tape bands transversely apart. The spaced bands are attached to a sheet form elastic web to form a stretchable fastener product. In some examples, the stretchable fastener product is formed continuously in conjunction with manufacture of the sheet-form fastener tape.
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FIELD OF THE INVENTION
This invention relates to burial caskets, and more particularly, to an improved mechanism for locking the lid of a casket to the body of the casket.
BACKGROUND OF THE INVENTION
Burial caskets include a lid hingedly connected to a body along one longitudinal edge, to permit hinged movement of the lid to a closed position along the other longitudinal edge. The lid and the body include structural components which cooperate to permit the lid to be locked, or tightly sealed, to the body in the closed position so that the closed casket is airtight.
When the casket is initially closed, the body and the lid are in uninterrupted engagement along confronting flange surfaces which extend completely around the four walls of the casket. A compressible gasket or sealing tube also extends completely around the casket and resides between the engaged flange surfaces of the body and the lid. During locking, the lid is pulled downwardly toward the body to compress the gasket and to provide an airtight seal extending completely around the four walls of the casket.
For metal caskets, a wedge bar is commonly used to lock the lid to the body. The wedge bar resides within a hollow portion of the body of the casket, adjacent the flange, and it extends almost the entire length of the open, or nonhinged, side of the casket. Hangers located inside the body hold the wedge bar at a desired vertical position, but allow horizontal movement along the axis of the wedge bar. The wedge bar includes at least one, and preferably three or four, catches having cam surfaces. The catches may be integrally formed with the wedge bar or separately attached thereto. Each catch resides immediately below a small opening in the flange along the nonhinged edge of the body. The nonhinged edge of the lid includes a corresponding number of keeper elements mounted thereto and directed downwardly, and these elements are aligned with the openings and catches. When the lid is closed, the keeper elements extend downwardly through the openings, with each keeper element positioned adjacent a catch.
Longitudinal movement of the wedge bar in a first direction toward a first end wall of the casket causes the catches to engage the keeper elements, and the keeper elements are cammed downwardly by the catches until the wedge bar stops moving. This camming action pulls the lid downwardly to the sealed position. A screw mounted within the body has a head end which is accessible through a port in the first end wall. This screw operatively connects to one end of the wedge bar, and the screw is held in place relative to the body by a bracket, which is fixedly secured to the body. Rotating the screw in one direction moves the wedge bar toward the first end wall, which locks the casket. Rotating the screw in an opposite direction moves the wedge bar toward the opposite end wall, which unlocks the casket. The screw is rotated from outside the first end wall, via the port therein.
Additional structural components are also housed within the body adjacent the first end wall, and these components are associated with the screw, the wedge bar or the bracket. These additional components are used to couple the screw to the wedge bar, to serve as a bearing therebetween, to prevent the wedge bar from rotating about its longitudinal axis, to prevent movement of the screw from its axis and to limit movement of the wedge bar toward or away from the first end wall during sealing or unsealing, respectively.
Burial caskets are typically displayed prior to being sold, so that the customer may select a preferred model. In displaying burial caskets, it is often necessary to demonstrate the locking capability. For some caskets, numerous demonstrations occur prior to sale. To maintain the reputation of the casket manufacturer, it is absolutely critical that the locking components perform repeated demonstrations without failing. The ability of the locking mechanism to perform repeated demonstrations without failure on one casket also provides a favorable indication that the same mechanism will not fail when used on other caskets, which for one reason or another may not be subjected to such demonstrations.
Additionally, regardless of whether or not the locking capability of a casket is publicly demonstrated, it is important that the casket remain locked in an airtight condition during actual use. Otherwise, a number of environmental and/or health concerns may arise, some of which are regulated by public law. These concerns are particularly relevant if the casket, in actual use, is not buried in the ground but simply placed in a mausoleum. Thus, the combination of structural components associated with locking and unlocking a casket must perform reliably and must hold up over an extended period of use.
In one prior locking casket locking design, seven separate parts are used to accomplish the above-described functions, excluding the wedge bar itself and fastening screws used to hold the bracket to the body. More specifically, this prior design uses a rivnut to couple the screw to the wedge bar. This rivnut is press fit into the end of the wedge bar and threadably receives an externally threaded screw. The screw also extends through a washer, a hole in one end wall of the bracket and a stop collar prior to threadable connection to the rivnut. The washer serves as a bearing surface between the rotatable screw and the fixed bracket. A roll pin secures the stop collar to the screw. A rivet secures to the wedge bar, and the rivet includes a head end which extends through a horizontal channel cut in a side wall of the bracket. This rivet and channel prevent twisting of the wedge bar during rotation of the screw.
While this design has generally been acceptable in use, there is room for improvement. Namely, the stop collar and roll pin connected to the screw have been susceptible to failure. Also, coupling of the screw to the wedge bar requires machining and connecting the rivnut. Additionally, the rivet/channel structure for preventing twisting of the wedge bar requires several machining steps to form these parts, followed by the assembly steps of connecting and extending the rivet through the channel and connecting it to the wedge bar, with the wedge bar in place. In sum, the use of these seven separate parts for the purpose of locking and unlocking a casket represents a disproportionately high cost to the manufacturer, and ultimately to the consumer, particularly when considering that this design has failed on some occasions.
It is an object of this invention to significantly reduce the failure susceptibility of the structural components used to lock and unlock a burial casket.
It is another object of this invention to reduce the number of parts used to lock and unlock a burial casket, without sacrificing structural integrity or performance quality.
It is still another object of the invention to reduce the costs associated with manufacturing and assembling the components used to lock and unlock a casket.
SUMMARY OF THE INVENTION
This invention meets the above-stated objectives by using a simpified casket locking/unlocking mechanism of three-piece construction which includes a modified bracket, a modified screw and a bearing or retainer clip. The cooperative interaction of the bracket, the screw and the clip not only affects longitudinal movement of the wedge bar, but it also prevents twisting of the wedge bar, limits longitudinal movement of the wedge bar in both directions, limits movement of the screw from its axis and provides a bearing surface between the rotatable screw and the fixed bracket.
The three-piece locking/unlocking mechanism of this invention has a high degree of structural integrity, due to the manner in which the components cooperate to provide the above-described functions. As a result, compared to prior casket locking designs, this invention reduces the susceptibility for failure. This invention also represents an improvement over prior designs because enhanced structural integrity is achieved with fewer parts. Specifically, this invention eliminates the stop collar and the roll pin of the above-described prior design, the parts most susceptible to failure. Due to the reduction in parts, this invention also reduces the costs associated with manufacturing and assembling the components used to lock and unlock a burial casket.
According to a preferred embodiment of the invention, a wedge bar locking mechanism for a burial casket includes a screw with a reduced diameter forward end or pin, an externally threaded portion, an integral collar, a reduced diameter midportion and a smooth rearward portion which houses an Allen head. The bracket includes inner and outer vertical end walls integrally connected with a center wall. The center wall includes inner and outer pairs of spaced integral tabs. The inner end wall includes a hole sized to receive the pin located at the forward end of the screw. The outer end wall includes an upwardly opening slot sized to receive the midportion of the screw, with a cutout region thereabove. Both vertical end walls have an inwardly turned horizontal flange with a hole therein for fastener screws for securing the bracket to the body. The clip is made of bronze and includes two integral side members folded along one edge, with a slot cut into the opposite edge. In use, the slot opens downwardly.
The end of the wedge bar includes a pair of parallel vertical, spaced sections oriented perpendicular to the first end wall of the casket, with an interconnecting vertical section therebetween which is oriented parallel to the end wall of the casket. The interconnecting section has an internally threaded hole sized to receive the threaded portion of the screw.
The screw extends through the upwardly opening slot and the cutout in the outer vertical wall of the bracket, and the threaded portion is threaded through the hole in the interconnecting section of the wedge bar, so that the pin at the forward end is receivably retained in the reduced-diameter hole in the inner vertical wall of the bracket. In this position, the smooth outer portion of the screw is then lowered downwardly to locate the midportion within the slot in the outer vertical wall of the bracket. This locates the integral collar of the screw inside the outer wall and the rearward portion of the screw outside thereof. The bronze clip is moved downwardly over the outer end wall through the cutout region to place the downwardly directed slot over the screw midportion, with both side members sandwiching the outer wall and in turn being sandwiched between the collar and the outer smooth portion of the screw. The oppositely directed slots of the clip and the outer vertical wall completely encircle the midportion of the screw.
With the bracket secured to the body of the casket and the outer end of the screw accessible through a keyway in an end wall of the casket, this mechanism is ready to be used to reciprocally move the wedge bar horizontally along its axis to cause locking and unlocking of the casket. Rotation of the screw causes movement of the wedge bar.
Together, the captured pin at the forward end of the screw and the body of the casket itself prevent radial movement of the screw from its axis of rotation. The screw collar, midportion and outer portion coact with the outer wall of the bracket to prevent linear movement of the screw along its axis. The clip further restricts longitudinal, or axial, movement of the screw, provides quiet operation and also inhibits rust buildup. The inner and outer pairs of tabs of the center wall of the bracket limit longitudinal over-travel of the wedge bar away from and toward the first end wall of the casket, respectively. The inner vertical wall of the bracket, like each pair of tabs, has a width which is less than the spacing between the parallel sections of the wedge bar, so as not to prevent movement of the sections past the inner wall during unlocking movement of the wedge bar.
Also, the center wall is oriented perpendicular to the interconnecting section, and it has a width which is greater than the space between the parallel end sections of the wedge bar. With these parallel sections supported by, and in contact with, the center wall, the bracket prevents rotation of the wedge bar during rotation of the screw.
Thus, these three components form a wedge bar locking mechanism for a casket, and this mechanism performs all of the features required of casket locking and unlocking devices of this type. Namely, the mechanism controllably moves the wedge bar along its longitudinal axis for locking and unlocking, limits linear movement of the wedge bar past the locked and unlocked directions i.e. over-travel, prevents twisting of the wedge bar during screw rotation, and prevents the screw from moving radially or axially during rotation thereof.
Additionally, the wedge bar locking mechanism of this invention has improved structural integrity, fewer parts and lower manufacturing and assembly costs. The lower manufacturing costs result from the fewer number of components and the relatively simple manner in which the components of this mechanism may be produced. The lower assembly costs likewise result from the fewer number of components and the relatively straightforward manner in which these three components interact.
While the principles of this invention have been described with respect to a casket having a one-piece lid, it is to be understood that the invention also applies to caskets which use a lid with two separately foldable but connectable lid sections.
These and other features of the invention will be more readily understood in view of the following detailed description and the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a partially open casket, illustrating the environment of the present invention.
FIG. 2 is a transverse cross sectional view through a nonhinged edge of a closed casket, at one of the flange openings of the body, showing the relationship of the wedge bar and the rollers used to lock the casket closed.
FIG. 3 is a disassembled perspective view which shows a preferred embodiment of a wedge bar locking mechanism for a casket in accordance with a preferred embodiment of the invention.
FIG. 4 is a top view in partial cross section of the mechanism shown in FIG. 3, with the components of the wedge bar locking mechanism of this invention in an assembled condition.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 shows a burial casket 10 which may be equipped with the wedge bar locking mechanism of this invention. The wedge bar locking mechanism of this invention has particular advantages with respect to steel burial caskets, though the principles are also applicable to wooden burial caskets, or caskets made of any other suitable material, for that matter. The casket 10 includes a body 12 and a lid 14 hingedly connected to the body 12 along a hinge edge 16. The lid 14 closes upon the body 12 via hinged motion along the hinge edge 16, to place the body 12 and the lid 14 in contact along an opposite edge 18. A number of hinges 20 interconnect the body 12 and the lid 14 along the hinge edge 16, as is known in the industry.
The body 12 includes a flange 22, and the lid 14 includes a corresponding flange 24. The body flange 22 and the lid flange 24 reside in continuous engagement completely around the four walls of the casket 10 when the lid 14 is closed on the body 12. A compressible gasket (not shown) resides between the confronting flanges 22 and 24, as is known in the industry. The lid 14 includes a number of pulldown fasteners 25, mounted adjacent second edge 18. FIG. 1 shows four pairs of such pulldown fasteners 25 which are equally spaced along edge 18. Each fastener 25 preferably includes a pair of spaced studs 26 which hold a roller 28 therebetween, with the roller 28 oriented transverse to the longitudinal dimension of the casket 10. On the body 12, the flange 22 includes a like number of openings 30, and each opening 30 corresponds to one of the fasteners 25. Upon closing of the lid 14 to the body 12, the studs 26 and the rollers 28 associated therewith extend downwardly through the openings 30.
The body 12 of the casket 10 is further defined by a first end wall 32 and a second, opposite end wall 34. The first end wall 32 includes a keyway 33 located just below the horizontal surface of the body flange 22.
As shown more clearly in FIG. 2, with lid 14 closed on body 12, each pair of studs 26 and the roller 28 associated therewith extends downwardly through one of the openings 30 in the body flange 22. A wedge bar 36 extends longitudinally along the length of the casket 10 along first edge 18. The wedge bar 36 resides below body flange 22 and within a recess or cavity 37 in the body 12. The wedge bar 36 is held at a desired vertical level within this opening 37 by hangers (not shown) which permit reciprocal motion of the wedge bar 36 along its longitudinal axis, or parallel with second edge 18.
This motion of wedge bar 36 causes locking and unlocking of the lid 14 to the body 12. More specifically, the wedge bar 36 includes a number of cutout regions which define catches 38, and each catch 38 corresponds to an opening 30 and an associated roller 28. Each catch 38 is defined in shape via a tapered edge 40 which serves as a cam surface and cooperates with a respective roller 28, which serves as a cam. When the wedge bar 36 moves longitudinally toward first end wall 32, the catches 38 engage the rollers 28 and gradually pull them downwardly, at a rate and distance dependent upon the angle of the tapered edges 40. This downward pulling of the rollers 28 also pulls the lid 14 downwardly with respect to body 12 so that their corresponding flanges 24 and 22 are compressed along second edge 18, along with the other three edges of the casket 10. This downward pulling compresses the gasket (not shown) residing between the body 12 and the lid 14 to lock the casket 10 in a sealed, airtight condition.
To unlock the casket 10, the wedge bar 36 is moved longitudinally in a direction away from first end wall 32, or in the direction toward second end wall 34. This causes the catches 38 to disengage the rollers 28, which allows the lid 14 to be lifted with respect to the body 12. The components and operation described thus far are well known in the burial casket industry, and do not form part of the present invention. The present invention relates to the simplification and improvement of the mechanism or components which affect longitudinal movement of the wedge bar 36 with respect to the body 12, and the other functions associated therewith.
More particularly, FIG. 3 shows the components which make up this invention. According to the invention, a wedge bar 36 has a first end designated generally by reference numeral 42. This first end 42 includes an offset region 44 which primarily provides additional strength for the wedge bar 36. Adjacent the offset region 44, the first end 42 includes first and second spaced parallel sections 46 and 48, preferably vertically oriented, with an interconnecting section 50 spanning therebetween, also preferably vertically oriented. The interconnecting section 50 includes an internally threaded hole 52. The sections 46 and 48 are also perpendicular to end wall 32, while section 50 is parallel thereto. Preferably, the wedge bar 36 is formed to the configuration shown in FIG. 3 via a number of cutting and stamping steps, as known in the industry.
A bracket 54 is fixedly mounted to the body 12 adjacent the first end 42. The bracket 54 includes inner and outer vertical walls 56 and 58, respectively, each of which includes an upper horizontal flange 57 and 59, respectively. The inner wall 56 is further from first end wall 32 than outer wall 58. The width of inner wall 56 is less than the spacing between the first and second end sections 46 and 48, so as to not obstruct movement of the wedge bar 36 away from the first end wall 32 of the casket 10.
The inner wall 56 and outer wall 58 are interconnected by a center wall 60. In FIG. 3, the center wall 60 is horizontal, so as to be oriented perpendicular to the parallel sections 46 and 48. If the first end 42 is configured so that first and second sections 46 and 48 are horizontal, then center wall 60 should be vertical. The center wall 60 has a width greater than the spacing between the space between the parallel end sections 46 and 48, thereby to engage and to prevent rotational movement of the wedge bar 36 in either direction.
The center wall 60 includes a first inner pair of integral bent tabs 61 and a second outer pair of integral bent tabs 63. The pairs of tabs 61 and 63 also have a transverse spacing which is less than the spacing between parallel sections 46 and 48. The inner vertical wall 56 includes a hole 62, and the outer vertical wall 58 includes an upwardly opening slot 64, and a cutout region 65 located thereabove. The hole 62 and slot 64 are aligned along an axis 66. When the bracket 54 is secured to a bottom inside surface of body flange 22, via screws (not shown) which thread through the holes in horizontal flanges 57 and 59, the wedge bar 36 is arranged such that the interconnecting end section 50 resides adjacent center wall 60. Also, the threaded hole 52 in the interconnecting section 50 of the wedge bar 36 is aligned along axis 66 with hole 62 and slot 64. The axis 66 is also aligned with the keyway 33. The bracket 54, like the wedge bar 36, is formed via a number of punching and bending operations performed on a single piece of sheet metal.
A screw 68 also aligned with the keyway 33 operatively connects to the bracket 54 and the wedge bar 36. More particularly, the screw 68 includes a rearward end or portion 70 with an Allen head 71 located inside thereof, and a forward threaded portion 72. A reduced diameter pin 73 extends beyond threaded portion 72, at the forwardmost or inner end of the screw 68. This pin 73 is sized to be received within the hole 62 in the inner vertical wall 56. Screw 68 further includes an integral collar 74 located adjacent threaded portion 72, and a reduced diameter midportion 76 resides between the collar 74 and the rearward smooth portion 70.
Screw 68 is preferably formed by machining a blank on a screw machine. The initial machining step creates the collar 74 and the reduced diameter midportion, along with pin 73. The rearward smooth portion 70 is end drilled and then broached to form the transverse hexagonal shape of the internal Allen head. Thereafter, portion 72 is roll threaded, preferably in a manner which results in screw threads with a dimension of 7/16" or #5 Acme.
A bronze clip 78 includes inner and outer integral side members 80 and 82 folded along one edge and each cut to form a slot 84 located at an opposite edge, the slot 84 having an upper arcuate edge cut therein. In use, the slot 84 is downwardly directed. The clip 78 is sized so as to extend downwardly so that the inner and outer folded members 80 and 82 tightly sandwich the outer vertical wall 58, and the downwardly directed slot 84 closes off the upwardly directed slot 64, thereby encircling the midportion 76 of the screw 68. This relationship is shown most clearly in FIG. 4. FIG. 4 also shows that the longitudinal dimension of reduced diameter midportion 76 is sufficient to accommodate the combined longitudinal dimension of the clip 78 and the outer vertical wall 58. The clip 78 holds the screw 68 in place with respect to body 12 during rotational movement in either direction, to prevent axial movement thereof. The clip 78 is preferably formed by stamping and then folding a bronze blank. The invention contemplates the use of a clip 78 made of any material suitable for withstanding the necessary manufacturing steps of a casket, such as heat treatments, and also suitable for providing a quiet operation while inhibiting rust buildup. However, applicant is not presently aware of any material other than bronze which is suitable.
With the pin 73 residing in hole 62 and the clip 78 coactng with wall 58, the screw 68 is prevented from moving either axially or radially, and only rotational movement is permitted. The screw 68 may be rotated with an Allen head wrench via extension of the wrench through keyway 33. Because the forward threaded portion 72 extends through the threaded hole 52 of wedge bar 36, and because the screw 68 is prevented from moving axially or radially from longitudinal axis 66, rotation of the screw 68 causes longitudinal movement of the wedge bar 36 with respect to the body 12. Because the center wall 60 of bracket 54 has a width which is greater than the spacing between the first and second parallel sections 46 and 48 of wedge bar 36, the bracket 54 restricts twisting in either direction of wedge bar 36 about its longitudinal axis during rotation of the screw 68.
Additionally, the spaced pairs of integral tabs 61 and 63 serve as mechanical stops which limit longitudinal movement of wedge bar 36 via contact with interconnecting section 50. More specifically, when screw 68 is rotated to move wedge bar 36 toward second end wall 34, the transverse spacing between the first pair of tabs 61 and the width of the inner vertical wall 56 are both less than the spacing between parallel sections 46 and 48, so movement is permitted. However, if movement of wedge bar 36 continues, interconnecting section 50 eventually contacts the pair of tabs 61, and is prevented from further movement toward the second end wall 34 of the casket 10. This corresponds to the rollers 28 being out of engagement with the catches 38, so that the lid 14 may be lifted with respect to the body 12. When the screw 68 is rotated in the opposite direction, so that the wedge bar 36 moves toward first end wall 32 to lock the lid 14 to the body 12, interconnecting section 50 eventually contacts the outer pair of tabs 63 and is prevented from further movement. This corresponds to complete camming down of the rollers 28 by the catches 38, when the lid 14 is locked to the body 12.
Thus, the three-component mechanism structure shown in FIGS. 3 and 4 effectively moves the wedge bar 36 along its axis as needed to lock and unlock the lid 14 of the casket 10 to the body 12 of the casket 10. Namely, these components threadably engage the wedge bar 36 to convert rotational movement of screw 68 into longitudinal movement of the wedge bar 36. These components also: 1) restrict the wedge bar 36 from twisting during longitudinal movement; 2) limit longitudinal over-travel of the wedge bar 36 in both the locked and unlocked directions; 3) prevent axial and radial movement of the screw 68; and 4) provide a bearing surface between the rotatable screw 68 and the nonrotatable components, for smooth and quiet operation, with reduced rust buildup.
One primary advantage of this invention relates to the ability of this wedge bar locking mechanism to provide all of these necessary features with a minimal number of parts, Excluding the wedge bar 36 and mounting screws, these features are provided by only three other components, i.e. the bracket 54, the screw 68 and the clip 78. In contrast, the prior art described in the background section required seven parts.
Because of this reduction in the number of necessary components, and further because of the manner in which these particular parts interact, this invention significantly reduces the possibility for failure of the wedge bar mechanism used to lock and unlock a casket 10. Moreover, because of th minimal number of components, this invention reduces the time and cost associated with manufacturing and then assembling a wedge bar locking mechanism.
While a wedge bar locking mechanism in accordance with a preferred embodiment of the invention has been described, it is to be understood that the invention is not limited thereby and that in light of the present disclosure, various other alternative embodiments will be readily apparent to one of skill in the art without departing from the scope of the invention. Accordingly, applicant intends to be bound only by the following claims.
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An improved wedge bar locking mechanism for a burial casket requires only a bracket, a screw and a clip which cooperate with one end of a wedge bar to cause longitudinal movement of the wedge bar in two directions for locking end unlocking the lid of a casket to the body of the casket. The components of the mechanism are located in the body of the casket, adjacent an end wall. The bracket mounts rigidly to the body. The screw threads directly to the wedge bar, and the bracket and clip hold opposite ends of the screw to prevent axial and radial movement thereof so that rotational movement of the screw is converted to longitudinal movement of the wedge bar. The screw is accessible for rotation via a keyway in the end wall. A center wall of the bracket engages the end of the wedge bar to prevent rotational movement thereof when the screw is rotated. The bracket also includes integral tabs which serve as over-travel stops for both the locked and unlocked positions of the wedge bar. This improved mechanism is less susceptible to failure than prior structures, and it requires fewer components, which translates to a cost savings due to reduced manufacturing and assembling expense.
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RIGHTS OF THE GOVERNMENT
The invention described herein may be manufactured and used by or for the Government of the United States for all governmental purposes without the payment of any royalty.
BACKGROUND OF THE INVENTION
This invention relates generally to the field of protective outer surface structures or casings for spacecraft, aircraft, missiles, or the like, configured for resistance to radiation damage, and more specifically, to an improved missile casing structure or the like which is hardened against damage by laser radiation.
Modern developments in laser technology and the concomitant application thereof to weapon systems has necessitated intense development of protective countermeasures to render missile and other weapon systems substantially invulnerable to laser attack. By necessity, the structure defining the outer shell or casing for missiles, aircraft, spacecraft or the like which contain and protect the critical components of the airborne systems, including the propulsion and guidance systems, the fuel, and payload, must therefore, be configured for hardening against the effects of high intensity laser irradiation. Preferably, the laser hardened protective structure for a missile will not substantially compromise total system cost or weight considerations.
Prior art structures configured to provide resistance to the effects of laser or other potentially damaging radiation have included various highly reflective surfaces and heat resistant coatings or paints, and metal, ceramic or resin composites, representative of which may be that disclosed by or referenced in: U.S. Pat. No. 4,008,348 to Slemp describing a laminated coating comprising a particulate radiation stable coating over a transparent solar radiation film having a mirror reflecting metal deposited on the bottom thereof; U.S. Pat. No. 4,041,872 to McCown et al describing a layered shield for a housing comprising a tin sheet overlaid with a glass filament reinforced resin matrix composite and sprayed with an external ablative insulation; U.S. Pat. No. 3,712,566 to Branen et al describing a thermal protective coating of silica cloth impregnated with a phenolic resin; U.S. Pat. No. 4,268,562 to Bacon et al describing an alumina fiber reinforced ceramic composite having two series of alumina fibers oppositely oriented in the composite; and U.S. Pat. No. 3,986,690 to Milling describing a retroreflective aluminum structural surface positioned beneath the outer skin of an aircraft.
Existing laser resistant surface configurations, however, do not adequately provide the necessary hardening to laser penetration of the casing structure for critical components of a missile or the like.
The present invention, however, provides a laser hardened case structure for a missile or the like substantially reducing the vulnerability of the missile to laser attack without substantial cost or weight penalty to the missile system.
It is, therefore, an object of the present invention to provide a laser hardened, protective casing structure for a ballistic missile or the like.
It is a further object of the present invention to provide a lightweight, low cost protective casing for a missile or the like which is resistant to laser attack.
These and other objects of the present invention, as would occur to one with skill in the applicable fields, will become apparent as the detailed description of certain representative embodiments thereof proceeds.
SUMMARY OF THE INVENTION
In accordance with the foregoing principles and objects of the present invention, a laser hardened casing structure for a missile or the like is described herein which comprises, in a preferred embodiment, a pair of thermally protective layers with a laser hardened barrier layer sandwiched therebetween and comprising a heavy metal bearing resin impregnated carbon fabric, all of said layers being adhesively joined and secured to the outer surface of the casing structure to be protected.
DESCRIPTION OF THE DRAWINGS
The present invention will be more clearly understood and appreciated from a reading of the following detailed description of specific representative embodiments thereof in conjunction with the accompanying drawings wherein:
FIG. 1 is a sectional view of a conventional fiberglass casing structure for a fuel tank having a thermally protective outer layer.
FIG. 2 is a sectional view of a fiberglass casing having an outer protective layered structure incorporating the novel laser hardened barrier layer of the present invention.
DETAILED DESCRIPTION
Referring now to the drawings, FIG. 1 shows in cross section the layered structure of an existing missile casing, generally designated as casing structure 10. The conventional structure of casing 10 of FIG. 1 may comprise an outer layer 11 typically of a cork composition such as cork phenolic, cork epoxy, or cork nitrile. Outer layer 11 functions generally as a thermal protective layer for the remainder of the casing structure, and may comprise in alternate configurations carbon phenolic, silica phenolic, carbon nitrile, or epoxy novalac coatings, ranging in thickness from about 0.1 cm to about 1.0 cm.
Outer layer 11 is adhesively bonded to fiberglass composite missile structural member 12 using conventional bonding agents. Structural member 12 of the conventional structure shown in FIG. 1 comprises fiberglass, although other materials such as Kevlar® fibers, graphite fibers, or the like, may be applicable, depending on the system encased, to provide the desired structural strength to casing 10. FIG. 1 also shows the location of a fuel sealant liner 13, representative of the use of a casing 10 for the protection of a fuel containment system.
FIG. 2 illustrates a representative embodiment of the novel laser-hardened protective structure of the present invention as applied to the protection of the casing 20 for such as a fuel containment system. As shown in FIG. 2, the missile casing may comprise a fiberglass structural member 22 for enclosing the fuel containment system including a fuel sealant liner 23. The novel laser hardened protective covering hereinafter described may be applied to various casing materials and configurations which, it should therefore be noted, are not limiting of the invention herein.
The novel laser hardened protective structure of the present invention may comprise, as shown in the representative embodiment of FIG. 2, a pair of thermal protection layers 24 and 25 of cork composition, cork phenolic, cork epoxy, cork nitrile, or other mentioned conventionally used thermal protection material, or like materials which may exhibit ablative character upon exposure to high temperature. Layers 24 and 25 may each be from about 0.1 cm to about 1.0 cm in thickness, and preferably from about 0.05 cm to about 0.5 cm.
Sandwiched between layers 24 and 25 is unconventional laser hardening barrier 26. Barrier 26 may generally comprise a heavy metal bearing resin impregnated carbon fabric. The heavy metal may be in the form of powder or granules, and is preferably in the form of a resin dispersion. The heavy metal, preferably tungsten, may be carried by a resin such as epoxy, acrylic, ester, or amide, the resin-heavy metal mixture being impregnated into woven fabrics of carbon pitch fibers or carbon thread, or directly in the form of treated carbon filaments. Fully satisfactory casing structures 20 were fabricated including as the laser barrier 26 a single ply thickness of tungsten bearing resin impregnated carbon cloth which is graphitized at about 2800° C. in an inert gas environment, available commercially from Hitco Corporation, of Gardena, Calif., as Hitco TBR/SWB-8 (2800° C.). The thickness of layer 26 may be from about 0.02 cm to about 0.1 cm. Further, a plurality of individual layers 26 may be desirable.
Layers 24, 25 and 26 may be bonded together using any suitable temperature resistant adhesive, such as epoxy, acrylic or amide.
Test specimens (cut to 2.5×2.5 cm) of the layered casing structure 20 were prepared for destructive testing and comprised a painted external cork layer 24, the Hitco TBR material as layer 26, and a second cork layer 25. The layers 24, 26, and 25 were bonded together and to a fiberglass structural member 22 using Devcon five-minute epoxy adhesive. Thermocouples (chromel-alumel, type K) were imbedded between the cork layer 25 and the fiberglass structural member 22. The thermocouples provided temperature-time histories for the test specimens during laser irradiation tests described below. During fabrication, the thermocouple leads were laid in the bond line between cork layer 25 and fiberglass structural member 22 to minimize the effects on the tests of heat conduction along the thermocouple lead wires. The layers of the test specimens were clamped together at moderate pressure to minimize distortion of the cork composition layers during adhesive cure.
The specimens were distructively tested to determine the effects of laser irradiation on the structure in the simulated environment of a wind tunnel. The laser system used for the tests was an electric discharge convective continuous wave carbon dioxide laser having the following operating characteristics:
Wavelength: 10.6 microns
Power output: 11 kilowatts
Beam divergence: 3.7 milliradians
The laser beam was circular in cross section and had a substantially uniform intensity profile with a maximum deviation in local power intensity of less than about ±12% from the mean average power intensity of the entire beam. Energy measurements on the laser were made using an absorptive calorimeter. Statistically, measurements of laser energy had an uncertainty of about ±11.68%. The incident beam energy was directed at an angle of about 10° from the normal to the exposed specimen surface in a direction downstream in the wind tunnel flow.
The wind tunnel used was a blowdown type using a 5×10 cm discharge nozzle. The wind tunnel test configuration comprised channel flow with nitrogen gas flowing tangentially across the irradiated specimen face at about Mach 0.1. The specimen was positioned at 5.5 cm downstream of the wind tunnel nozzle outlet. Under these flow conditions, the dynamic gas shear stress at the specimen surface was calculated to be approximately 290 dynes/m 2 . The mass transfer coefficient was calculated to be approximately 0.098 Kg/m 2 sec.
A plurality of such test specimens as described above were destructively tested by laser irradiation using the carbon dioxide laser at a power level of up to about 5000 watts/cm 2 . In all cases, the specimens were irradiated sufficiently for the outer cork composition layer 24 to be substantially fully ablated. Delamination of the cork and TBR layers occurred in one specimen. However, in all cases, no indication of ablation of the laser barrier layer was evident.
The present invention, as herein described, therefore provides a novel laser hardened structure for protection of surfaces of missiles or the like. The layered configuration of this invention permits erosion and ablation of the outer thermal protection layer during substantial temperature excursions, such as might occur during launch, laser or other radiation exposure, aerodynamic heating, etc., without compromising the laser hardening character of the barrier.
It is understood that certain structural modifications and material substitutions may be made as might occur to one with skill in the field of this invention, within the scope of the appended claims. Therefore, all embodiments contemplated hereunder have not been shown in complete detail. Other embodiments may be developed without departing from the spirit of this invention or from the scope of the appended claims.
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A laser hardened casing structure for a missile or the like is described herein which comprises, in a preferred embodiment, a pair of thermally protective layers with a laser hardened barrier layer sandwiched therebetween and comprising a heavy metal bearing resin impregnated carbon fabric, all of said layers being adhesively joined and secured to the outer surface of the casing structure to be protected.
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BACKGOUND OF THE INVENTION
[0001] This invention relates generally to the field of phacoemulsification and more particularly to torsional phacoemulsification cutting tips.
[0002] The human eye in its simplest terms functions to provide vision by transmitting light through a clear outer portion called the cornea, and focusing the image by way of the lens onto the retina. The quality of the focused image depends on many factors including the size and shape of the eye, and the transparency of the cornea and lens.
[0003] When age or disease causes the lens to become less transparent, vision deteriorates because of the diminished light which can be transmitted to the retina. This deficiency in the lens of the eye is medically known as a cataract. An accepted treatment for this condition is surgical removal of the lens and replacement of the lens function by an IOL.
[0004] In the United States, the majority of cataractous lenses are removed by a surgical technique called phacoemulsification. During this procedure, a thin phacoemulsification cutting tip is inserted into the diseased lens and vibrated ultrasonically. The vibrating cutting tip liquifies or emulsifies the lens so that the lens may be aspirated out of the eye. The diseased lens, once removed, is replaced by an artificial lens.
[0005] A typical ultrasonic surgical device suitable for ophthalmic procedures consists of an ultrasonically driven handpiece, an attached cutting tip, and irrigating sleeve and an electronic control console. The handpiece assembly is attached to the control console by an electric cable and flexible tubings. Through the electric cable, the console varies the power level transmitted by the handpiece to the attached cutting tip and the flexible tubings supply irrigation fluid to and draw aspiration fluid from the eye through the handpiece assembly.
[0006] The operative part of the handpiece is a centrally located, hollow resonating bar or horn directly attached to a set of piezoelectric crystals. The crystals supply the required ultrasonic vibration needed to drive both the horn and the attached cutting tip during phacoemulsification and are controlled by the console. The crystal/horn assembly is suspended within the hollow body or shell of the handpiece by flexible mountings. The handpiece body terminates in a reduced diameter portion or nosecone at the body's distal end. The nosecone is externally threaded to accept the irrigation sleeve. Likewise, the horn bore is internally threaded at its distal end to receive the external threads of the cutting tip. The irrigation sleeve also has an internally threaded bore that is screwed onto the external threads of the nosecone. The cutting tip is adjusted so that the tip projects only a predetermined amount past the open end of the irrigating sleeve. Ultrasonic handpieces and cutting tips are more fully described in U.S. Pat. Nos. 3,589,363; 4,223,676; 4,246,902; 4,493,694; 4,515,583; 4,589,415; 4,609,368; 4,869,715; 4,922,902; 4,989,583; 5,154,694 and 5,359,996, the entire contents of which are incorporated herein by reference.
[0007] In use, the ends of the cutting tip and irrigating sleeve are inserted into a small incision of predetermined width in the cornea, sclera, or other location. The cutting tip is ultrasonically vibrated along its longitudinal axis within the irrigating sleeve by the crystal-driven ultrasonic horn, thereby emulsifying the selected tissue in situ. The hollow bore of the cutting tip communicates with the bore in the horn that in turn communicates with the aspiration line from the handpiece to the console. A reduced pressure or vacuum source in the console draws or aspirates the emulsified tissue from the eye through the open end of the cutting tip, the cutting tip and horn bores and the aspiration line and into a collection device. The aspiration of emulsified tissue is aided by a saline flushing solution or irrigant that is injected into the surgical site through the small annular gap between the inside surface of the irrigating sleeve and the cutting tip.
[0008] One phacoemulsification tip that has gained widespread acceptance has a belled or flared distal end. Such a tip is described in U.S. Pat. No. 4,816,018 (Parisi). Such a design allows for larger lens material purchase as well as increased holding force when vacuum is applied to the tip while maintaining a smaller bore in the shaft of the tip. This combination of features increases anterior chamber stability, by reducing sudden outflow from the anterior chamber when the distal end becomes occluded and this occlusion breaks.
[0009] Another phacoemulsification tip is an angled or “bent” tip with or without a flared distal end. These tips are described in U.S. Pat. No. 6,039,715 (Mackool), U.S. Pat. No. 5,653,724 (Imonti) and U.S. Pat. No. 5,154,694 (Kelman). These tips have a predominantly straight shaft with the far distal portion of the shaft being bent on an angle. Bent tips are used by a great many surgeons, and are particularly useful when used in conjunction with a oscillatory phacoemulsification handpiece, such as those described in U.S. Pat. No. 6,352,519 (Anis, et al.) and U.S. Pat. No. 6,602,193 (Chon) and commercially available as the NeoSoniX® handpiece from Alcon Laboratories, Inc., Fort Worth, Tex., however; some surgeons are reluctant they feel that due to the proximal location of the bend it is more difficult to judge the position of the proximal cutting edge based on the extrapolation of the sleeved portion of the tip.
[0010] The inventors have discovered that angled phacoemulsification tip are particularly advantageous when used in combination with torsional ultrasound handpiece. Torsional ultrasound handpieces are more fully disclosed in U.S. Pat. No. 6,077,285 (Boukhny). Therefore, a need continues to exist for an angled phacoemulsification tip that is safer to use near the posterior capsule.
BRIEF SUMMARY OF THE INVENTION
[0011] The present invention improves upon the prior art by providing a phacoemulsification tip having an arched or curved shaft. Such a feature serves to produce more efficient cutting during torsional vibration of the tip while maintaining a greater space between the distal end of the tip and the posterior capsule.
[0012] Accordingly, one objective of the present invention is to provide a phacoemulsification cutting tip having increased efficiency, particularly during torsional ultrasound movement.
[0013] Another objective of the present invention is to provide a phacoemulsification cutting tip having a curved shaft.
[0014] These and other advantages and objectives of the present invention will become apparent from the detailed description and claims that follow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is a perspective view of the distal end of a typical prior art straight shaft phacoemulsification tip.
[0016] FIG. 2 is an elevational view the distal end of a typical prior art angled or bent phacoemulsification tip.
[0017] FIG. 3 is an elevational view the distal end of the phacoemulsification tip of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0018] As best seen in FIG. 1 , prior art phacoemulsification tip 10 contains shaft 12 that is straight all the way to distal tip 14 . As best seen in FIG. 2 , prior art phacoemulsification tip 100 contains shaft 112 that is straight up to distal end 113 . Distal end 113 is angled or bent on an angle relative to centerline 115 of shaft 112 from intersection 117 of shaft 112 and distal end 113 all the way to distal tip 114 .
[0019] The inventor has discovered that ultrasonic vibration of tip 1 10 causes a twisting of shaft 112 that is not present if tip 110 is rotarily oscillated. Such twisting causes distal tip 114 to assume a whipping motion which although less that the rotary motion generated in distal tip 114 when tip 110 is rotarily oscillated, the whipping motion greatly increases the cutting efficiency of tip 110 . As discussed above, lateral displacement L 1 of distal tip 114 from longitudinal centerline 115 of shaft 112 can place distal tip 114 near the posterior capsule during surgery, and the exact location of distal tip 114 can be difficult to determine. As a result, some surgeons prefer not to use a phacoemulsification tip of the design shown in FIG. 2 .
[0020] As best seen in FIG. 3 , phacoemulsification tip 210 of the present invention contains shaft 212 that is not straight but instead is bent on a slight arch along the entire length of shaft 112 . So constructed, lateral displacement L 2 of distal tip 214 from reference line 215 is less than lateral displacement L 1 of distal tip 114 from centerline 115 . Such a construction makes it easier for the surgeon to locate distal tip 214 and maintain a more comfortable distance from the posterior capsule during use, but still benefits from the increase cutting efficiency discussed above.
[0021] Cutting tip 210 is preferably made from stainless steel or titanium, but other materials may also be used. Cutting tip 210 preferably has an overall length of between 0.50 inches and 1.50 inches, with 1.20 inches being most preferred. Cutting tip 210 may be formed using conventional metalworking technology and preferably is electropolished to remove any burrs.
[0022] Shaft 212 is generally tubular, with an outside diameter of between 0.005 inches and 0.100 inches and an inside diameter of between 0.001 inches and 0.090 inches. Distal end 214 of shaft 212 may be cut square or cut at any suitable angle between 0° and 90°.
[0023] This description is given for purposes of illustration and explanation. It will be apparent to those skilled in the relevant art that changes and modifications may be made to the invention described above without departing from its scope or spirit.
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A phacoemulsification tip having an arched or curved shaft. Such a feature serves to produce more efficient cutting during torsional vibration of the tip while maintaining a greater space between the distal end of the tip and the posterior capsule.
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CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the priority of German Patent Application, Serial No. 10 2009 011 378.9, filed Mar. 5, 2009, pursuant to 35 U.S.C. 119(a)-(d), the content of which is incorporated herein by reference in its entirety as if fully set forth herein.
BACKGROUND OF THE INVENTION
[0002] The present invention relates, in general, to a door impact beam.
[0003] The following discussion of related art is provided to assist the reader in understanding the advantages of the invention, and is not to be construed as an admission that this related art is prior art to this invention.
[0004] Door impact beams are used in motor vehicles as door reinforcement to protect occupants from injury in the event of an impact from the side, and are typically made of tubes or tubular cross sections, for example extrusion profiles or also press parts. Tubular cross sections have the drawback that in areas in which stress is less they generally have a same cross section as in those areas which encounter maximum stress. For that reason, tubular profiles have been oversized in some areas. To optimize weight, it is therefore required to subsequently cut the tubular cross sections to size, causing separate manufacturing steps. This in turn adversely affects manufacturing costs.
[0005] It would therefore be desirable and advantageous to provide an improved door impact beam which obviates prior art shortcomings and is simple in structure with optimum weight and which can be produced in a cost-efficient manner.
SUMMARY OF THE INVENTION
[0006] According to one aspect of the present invention, a door impact beam for a motor vehicle includes a formed metal sheet defined by a longitudinal axis and having a tubular cross section which has a closed circumference in a center portion of the metal sheet, and is configured with open circumference at both end portions of the metal sheet which adjoin the center portion in a direction of the longitudinal axis, each said end portions defined by an opening angle which continuously increases from the center portion to respective ends of the end portions.
[0007] The final configuration of the door impact beam is already established by the contour of the metal sheet which has been cut to size, i.e. there is no need for a later manufacturing step. The weight is optimized therefore beforehand. The manufacturing process is more cost-efficient than would be the case when a tubular structure has to be cut to size later.
[0008] According to another advantageous feature of the present invention, a reinforcement plate can be arranged in the center portion along an inner side of the metal sheet and may extend about a circumferential area of less than 360°. The reinforcement plate bears flatly upon and is secured to the later inner side of the door impact beam of the metal sheet which is still unformed but cut to size. The reinforcement plate may be connected to the metal sheet by material union or formfittingly, e.g. through welding, clinching/compression. A subsequent forming step involved a forming of the patched metal sheet in such a way that the center portion has a closed cross section whereas the end portions have an open, round cross section. Also the reinforcement plate receives its final configuration during forming of the metal sheet. The forming process is preferably executed in two stages. In a first stage, the metal sheet is formed into a U-shape. The second stage involves the shaping into the partly closed O-shaped cross sectional contour.
[0009] The opening angle of the end portions increases from the central portion of the door impact beam to the ends of the end portions. The increase is advantageously continuous in the absence of jumps so as to prevent stress peaks. The cross sectional configuration, i.e. the radius, the elliptic or, when overlap is involved, helical contour of the cross section remains hereby preferably constant.
[0010] In an unformed initial state, the center portion of the metal sheet may have a rectangular geometry with preferably parallel length sides, followed in longitudinal direction by trapezoidal end portions, respectively, which taper to their free end.
[0011] The transition between the end portions and the central portion may be configured in such a way that the distance of the length sides of the end portions in this transition is smaller than a width of the center portion. Thus, there is a stepped width with a stepped jump in the transition. It is, of course, also conceivable to make the distance of the length sides the same as the width of the center portion.
[0012] The reinforcement plate arranged in the center portion of the door impact beam may conform to the geometry of the center portion and also configured in the form of a rectangle. In this case, the reinforcement plate is spaced from the length sides in the center portion and has a length which corresponds to 40% to 100%, preferably 40% to 70%, of a length of the center portion. A flat contact of the reinforcement plate upon the center portion provides a local reinforcement of the door impact beam at a location where maximum stress is encountered in the event of a side impact. The wall thickness of the metal sheet can be reduced by optimizing the cut and suitable positioning of the reinforcement plate, resulting overall in a weight reduction.
[0013] According to another advantageous feature of the present invention, the metal sheet may have length side zones which overlap in the center portion. It may also be conceivable to shape the metal sheet in such a way that the length sides are end-to-end in the center portion. Both cases result in a center portion of the door impact beam having the closed and in relation to the end portions more stable cross section for attaining the necessary stiffness. The length side zones or the length sides of the metal sheet can then be connected to one another, e.g. welding, locally in two regions through material union.
[0014] After the forming process, the end portions have a toroidal cross section. As a consequence of the trapezoidal shape of the end portions in the unformed state, an opening angle increases in a direction towards the free ends of the end portions. The opening angle may theoretically start at 0°, preferably it may start in a range from 10° to 100°. At the free ends of the end portions, the opening angle may range between 120° and 180°, so that the required stability of the door impact beam is still ensured also at the end portions. Advantageously, the opening angle is 180°. To optimize the door impact beam, the end portions may be configured differently, for example with respect to their length.
[0015] According to another advantageous feature of the present invention, the opening angle of the reinforcement plate, realized during forming, may be greater than the opening angle of the end portions in the transition to the center portion. In this way, the section modulus is especially high in the center portion. Of course, it is not precluded within the scope of the invention to select the angle identical or smaller when the door impact beam should be less stiff.
[0016] The geometry of the door impact beam is governed by the cut of the metal sheet so that additional refinishing operations can be omitted in order to optimize weight. It is also conceivable within the scope of the invention, to provide fastening brackets directly, when the metal sheet is cut to size, for allowing attachment of the door impact beam to a door structure. The fastening brackets are brought into the desired position, when the metal sheet is formed. Of course, it is also possible to provide fastening brackets as separate components on the free ends of the end portions. This causes, however, an additional manufacturing step.
BRIEF DESCRIPTION OF THE DRAWING
[0017] Other features and advantages of the present invention will be more readily apparent upon reading the following description of currently preferred exemplified embodiments of the invention with reference to the accompanying drawing, in which:
[0018] FIG. 1 is a schematic illustration of an unformed metal sheet for a door impact beam;
[0019] FIG. 2 is a side view of the metal sheet of FIG. 1 after undergoing a forming process;
[0020] FIG. 3 is a cross section of one variation of a formed metal sheet;
[0021] FIG. 4 is a cross section of another variation of a formed metal sheet;
[0022] FIG. 5 is a side view of a formed metal sheet;
[0023] FIG. 6 is a cross section of end portions of the metal sheet, taken along the line I-I in FIG. 5 ;
[0024] FIG. 7 is a cross section of end portions of the metal sheet, taken along the line II-II in FIG. 5 ;
[0025] FIG. 8 is a schematic illustration of a free end of an end portion; and
[0026] FIG. 9 is a schematic illustration of a formed metal sheet with press parts.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0027] Throughout all the figures, same or corresponding elements may generally be indicated by same reference numerals. These depicted embodiments are to be understood as illustrative of the invention and not as limiting in any way. It should also be understood that the figures are not necessarily to scale and that the embodiments are sometimes illustrated by graphic symbols, phantom lines, diagrammatic representations and fragmentary views. In certain instances, details which are not necessary for an understanding of the present invention or which render other details difficult to perceive may have been omitted.
[0028] Turning now to the drawing, and in particular to FIG. 1 , there is shown a schematic illustration of a metal sheet, generally designated by reference numeral 1 , in its still unformed initial state, for producing a door impact beam. The metal sheet 1 has a center portion 2 of rectangular shape. Adjoining both sides of the center portion 2 in longitudinal direction are trapezoidal end portions 3 , 4 , respectively. The end portions 3 , 4 have length sides 5 , 6 at distances A 1 , A 2 which are greater in a transition 7 to the center portion 2 than at the free ends 8 , 9 of the end portions 3 , 4 . In this non-limiting exemplified embodiment, the distances Al, A 2 for both end portions 3 , 4 are of same size. Of course, it is equally conceivable to make the distances from end portion to end portion different.
[0029] The distance A 2 of the length sides 5 , 6 in the transition 7 to the center portion 2 is smaller than a width B 1 of the center portion 2 . In accordance with another, not shown, embodiment, a distance of the length sides of the end portions may be made of same size in the transition to the center portion as the width of the center portion in order to attain a transition, substantially free of notch stress, from the end portions to the center portion.
[0030] A reinforcement plate 10 bears approximately in the middle of the center portion 2 flatly upon the later inner side 11 of the metal sheet 1 and has a length L 1 ( FIG. 2 ) which is about 50% of a length L 2 of the center portion 2 . In addition, the reinforcement plate 10 has a width B 2 which is smaller than a width B 1 of the center portion 2 so that the reinforcement plate 10 does not extend beyond the length sides 12 , 13 of the center portion 2 . As a result, the door impact beam is reinforced at a location where maximum stress can be expected.
[0031] FIG. 2 shows a side view of the metal sheet 1 after the latter has been shaped into a tubular profile with circular cross section. As a consequence of the trapezoidal configuration of the end portions 3 , 4 , the latter taper continuously starting from the transition 7 to the free ends 8 , 9 . The length sides 5 , 6 of the end portions 3 , 4 and an imaginary prolongation of the length sides 12 , 13 of the center portion 2 define hereby angles W 1 , W 2 , respectively, of at least 10° at the free ends 8 , 9 of the end portions 3 , 4 . The angles W 1 , W 2 of the end portions 3 , 4 may hereby differ, for example as a consequence of a different length of the end portions 3 , 4 . The door impact beam may therefore be configured asymmetric in relation to its transverse center axis MQE.
[0032] FIG. 3 shows a cross section of center portion 2 of a formed metal sheet 1 with a round, tubular cross section. The inner radius is designated with R. In this embodiment, the metal sheet 1 has been shaped in such a way that the length side zones 14 , 15 of the metal sheet 1 overlap. It can be seen that the reinforcement plate 10 does not extend beyond the length side zones 14 , 15 of the center portion 2 but rests evenly and flatly upon the inner side 11 of the metal sheet 1 . The opening angle W 3 of the reinforcement plate 10 and the radius R can be defined by the degree of overlap of the length side zones 14 , 15 .
[0033] A further possibility of a cross sectional configuration of the metal sheet 1 is shown in FIG. 4 . In this case, the metal sheet 1 is shaped in such a way that the length sides 5 , 6 are joined end-to-end. In this embodiment, the opening angle W 3 is greater than the opening angle W 3 of the reinforcement plate 10 of FIG. 3 .
[0034] The joining process for the embodiment of FIG. 3 as well as for the embodiment of FIG. 4 may be realized through material union for example.
[0035] FIG. 5 shows a side view of the formed metal sheet 1 of FIG. 4 with two section planes I-I and II-II.
[0036] FIGS. 6 and 7 show cross sections of the section planes I-I, of the end portions 3 , 4 of FIG. 5 . As can be seen, the opening angle W 4 of the end portions 3 , 4 is smaller in the transition 7 to the center portion 2 than the opening angle W 3 of the reinforcement plate 10 . As a consequence of the trapezoidal shape of the end portions 3 , 4 , the opening angle W 4 is greater to the free ends 8 , 9 than the opening angle W 3 of the reinforcement plate 10 , however not greater than 180°.
[0037] FIG. 8 shows a free end 16 of an end portion 17 formed in one piece with attachment brackets 18 for securement of the door impact beam to a door. The attachment brackets 18 may be provided already at a time when the basic shape of the unbent metal sheet is cut.
[0038] FIG. 9 shows a door impact beam in accordance with the invention with separate attachment brackets 19 at the free ends 20 , 21 of the end portions 22 , 23 for attachment to a door.
[0039] While the invention has been illustrated and described in connection with currently preferred embodiments shown and described in detail, 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 and scope of the present invention. The embodiments were chosen and described in order to explain the principles of the invention and practical application to thereby enable a person skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated.
[0040] What is claimed as new and desired to be protected by Letters Patent is set forth in the appended claims and includes equivalents of the elements recited therein:
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A door impact beam for a motor vehicle includes a formed metal sheet defined by a longitudinal axis and having a tubular cross section which has a closed circumference in a center portion of the metal sheet, and is configured with open circumference at both end portions of the metal sheet which adjoin the center portion in a direction of the longitudinal axis. Each end portion is defined by an opening angle which continuously increases from the center portion to respective ends of the end portions.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of application Ser. No. 09/378,885 filed on Aug. 23, 1999 which is a continuation-in-part of application Ser. No. 08/915,230, filed on Aug. 20, 1997, now U.S. Pat. No. 5,968,601, the disclosures of which are fully incorporated by reference herein.
[0002] This invention was made with Government support under Contract No. DE-FC07-941D13238 awarded by the Department of Energy. The Government has certain rights in this invention.
BACKGROUND OF THE INVENTION
[0003] The present invention generally relates to linear nozzles, i.e., nozzles having a straight, elongated opening, and a tailored gas plume exiting the nozzle for the entrainment and deposition of an atomized liquid material carried in the gas plume.
[0004] Linear nozzles can be used for producing spray formed sheet and plate, particularly aluminum sheet and plate, the nozzles depositing molten metal material on a planar surface and substrate. The substrate supports the molten metal until solidification, and acts as a heat sink in the cooling and solidifying process. Linear nozzles have the advantage of making the sheet at desired widths and at production rates that compete with the traditional breakdown and hot rolling of cast ingots. The molten metal is deposited by entrainment in a flow of a gaseous medium directed through the atomizing nozzle and to the substrate.
[0005] Linear nozzles can also be used to spray and deposit other atomizable liquid materials, such as coolants, paints, protective coatings or irrigants on the appropriate surfaces.
[0006] The velocity profile of the gas flow or plume exiting the nozzle determines the deposit profile independently of the configuration of the supply of liquid medium to the nozzle. In addition, it has been determined that a flat, gas plume will become axisymmetric (circular) downstream of the nozzle due to gas entrainment. Entrainment is more pronounced at the ends or edges of the nozzle so that the gas decelerates at a relatively faster rate at the ends or edges of the plume in comparison to rate of deceleration near and at the plume center. This phenomena is shown in FIG. 1 of the accompanying drawings. The result is a gaussian distribution of the liquid material on the substrate, as shown in FIG. 1.
[0007] Prior art efforts to overcome the problem has included the use of a plurality of axisymmetric nozzles scanning over the substrate. Other systems have included multiple nozzles to “fill in” low mass areas of the deposited material, while linear nozzles, using single chamber/single pressure schemes have involved changing the physical geometry of the gas exit of the nozzle for the purpose of controlling the distribution of deposited material. None of these efforts have produced the profile and yield properties needed at required production rates. “Yield” refers to the percent recovery of the liquid as a deposit.
SUMMARY OF THE INVENTION
[0008] By tailoring the gas velocity profile across the width of a linear nozzle, compensation for gas entrainment can be provided that ensures a substantially uniform deposit of the liquid material on a substrate. This can be accomplished by dividing the nozzle into compartments and directing gas flow through the respective compartments at conditions that will level or flatten the gas plume to make uniform the velocity of said gas plume at or near the point of liquid material deposition, thereby resulting in a more level or even deposition of said liquid material onto its substrate. The tailored gas configuration actually pushes downstream, or postpones, the natural tendency of a gaseous stream to assume an axisymmetric configuration and the resultant uneven (gaussian) deposit of liquid material on the substrate caused by an axisymmetric gaseous stream.
[0009] In a preferred embodiment, size of the individual chambers are controlled by partitions. These partitions are individually movable within the body of the nozzle to adjust and tailor the exit width of the gas leaving the compartments.
[0010] When creating long stretches of aluminum sheet or plate, the substrate can be moved relative to the nozzle at substantial speeds, or vice-versa, the nozzle can be moved, the process (again) providing an flatter, more planar deposit of liquid on the traveling substrate in both crosswise and lengthwise directions of the substrate. In this manner effective control of the gauge of the sheet or plate (after the liquid solidifies) is effected. Similarly, the embodiment can be used to provide an even application of other liquid metals or fluids.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The invention, along with its advantages and objectives, will be better understood from consideration of the following detailed description and the accompanying drawings in which:
[0012] [0012]FIG. 1 is a schematic representation of a prior art linear nozzle, the standard gas stream velocity profile out of the nozzle and the gas stream velocity profile downstream as it approaches a planar substrate to produce a deposit having a generally gaussian distribution of material on said substrate;
[0013] [0013]FIG. 2 is a schematic representation of a more recent art nozzle having an intentionally straightened gas stream velocity profile for minimizing the gaussian distribution of material deposited downstream on a substrate;
[0014] [0014]FIG. 3 shows a tailored gas profile downstream from a preferred linear nozzle according to this invention which gives a level, even or more consistently flatter deposit profile of material on its substrate;
[0015] [0015]FIG. 4 is an isometric exploded schematic representation of an elongated nozzle and plenum that has been partitioned with internal baffles or partitions and suppliable with individual gaseous streams provided under different pressures with a channel member;
[0016] [0016]FIG. 5 is a reverse view of the nozzle-plenum of FIG. 4 showing the internal baffles or partitions;
[0017] [0017]FIG. 6 is a diagrammatic representation of an apparatus for depositing molten metal, or any other depositable material, on a traveling substrate to make a solid sheet- or plate-like product from the nozzle of FIG. 5;
[0018] [0018]FIG. 7 is a top view of the nozzle plenum of FIG. 5;
[0019] [0019]FIGS. 8 a through 8 c are top views of three representative nozzle, baffle (or partition) and aperture configurations in accordance with this invention;
[0020] [0020]FIG. 9 is an isometric exploded schematic representation of an elongated nozzle and plenum that has been partitioned with internal baffles or partitions and suppliable with individual gaseous streams provided under different pressures with an alternative channel member; and
[0021] [0021]FIG. 10 is a plan view of the underside of the channel member shown in FIG. 9.
DESCRIPTION OF PREFERRED EMBODIMENTS
[0022] Referring now to the drawings, FIG. 1 shows the effects of the problem with linear gas nozzles 10 in depositing a material 12 on a surface 14 . Because of excessive deceleration of a gas stream 16 a near the ends of a linear nozzle, the configuration of the gas stream changes from an elongated to an arcuate pattern, as represented by downstream gas pattern 16 b , before reaching the substrate or target surface 14 . This, in turn, causes the gaussian, bell-shaped distribution of the deposited material shown in FIG. 1.
[0023] [0023]FIG. 2 shows schematically the effects of somewhat straightening, or flattening, the velocity profile of a gas 16 a exiting a nozzle 10 , resulting in subsequent gas pattern 16 b , for minimizing the gaussian distribution of material 12 being deposited on surface 14 .
[0024] [0024]FIG. 3 shows the preferred velocity profile 116 a of a gas exiting a linear nozzle 110 a in accordance with this invention, for achieving the desired subsequent gas pattern 116 b that results in a more evenly deposited material 112 a on planar surface 114 . This is effected by a gas velocity pattern that is relatively even but somewhat slower near the edge of the nozzle than the center portions of the nozzle, which are also relatively even except for a slight dip in velocity at the nozzle center.
[0025] The velocity of a gas stream across the width of a linear nozzle is produced and controlled by the pressure of the gas supplied to the nozzle. By adjusting gas pressure across the nozzle width, the profile, i.e., a gas plume 116 a , can be changed. FIGS. 4 and 5 show a sectionalized, elongated nozzle 110 a in which gas pressure and velocity can be selectively changed and controlled according to the invention. The lines midway through these depicted nozzles are meant to show that the invention may contain many more chambers than are actually depicted in the accompanying Figures. With respect to the fractionalized nozzle so depicted, gas is supplied thereto by a plurality of conduits 120 connected to a housing structure 122 . The housing structure has an interior 124 that provides an elongated plenum for receiving gas flows from the ends of the conduits connected to the housing. The gases are directed to the conduits from a supply thereof (not shown) under varying pressures to effect the plume 116 a shown in FIG. 3 of the drawings. In the preferred embodiment shown in FIG. 4, numerals P 1 to P 5 are used to designate five pressures of the gas flow through the five conduits 120 depicted. The gas pressure combination necessary to effect the uniform mass flow of fluid material 112 a on a planar substrate would have essentially equal pressures near the opposed ends (P 1 and P 5 ) of the linear nozzle, and equal pressures in the middle sections of the nozzle; the two sets of pressures are not equal to each other, however. Rather, the pressure at the ends of the nozzle are lower than the pressures adjacent the middle portion of the nozzle. The result is the velocity profile 116 a of FIG. 3.
[0026] To better control these pressures and the resultant gas velocity profile 116 a the plenum 124 of housing 122 can be provided with baffles or partitions 126 , as seen in FIG. 5 of the drawings. The partitions extend crosswise of the nozzle and plenum length between elongated walls of housing 122 and the elongated walls of an interior, vertical member 131 . Such partitions may be evenly spaced, or more preferably unevenly spaced apart as better seen in the subsequent views of FIGS. 5 and 7. The partitions provide side-by-side chambers that permit control of the velocity distribution of gas exiting the chambers through an aperture 132 (FIG. 4) discussed in detail hereinafter. Channel member 128 receives the material of deposit 112 in a fluid or molten form in the case of depositing metal on a substrate, for producing sheet and plate. The channel member is best seen in the exploded view of FIG. 4. Channel member 128 fits inside a built-in sleeve 131 of housing 122 , having a lower narrow neck portion 130 that enters and resides in plenum 124 . The lower end of the channel member has an elongated opening 136 (better shown in FIG. 7), and extends to and through an elongated opening 132 provided in a lower face plate 134 . Plate 134 closes the lower face of the plenum and housing around channel end 131 and thereby provides a narrow continuous closed loop aperture 137 (FIG. 7) that is elongated in the length direction of housing 122 and channel member 128 . Such an opening provides a curtain of gas in the configuration of the elongated closed loop of aperture 137 when gas is directed into plenum 124 that is directed from the plenum and towards a surface or substrate 114 (FIG. 6). In FIG. 5, the plate is removed from housing 122 to expose partitions 126 and vertical member 131 .
[0027] As further seen in FIG. 5, the ends of one or more conduits 120 are located between two consecutive partitions 126 to appropriately locate the flow of gas through the side-by-side chambers of plenum 124 and out of the continuous aperture 137 . This “location” of gas flow through the plenum and chambers and out of the continuous aperture 137 in combination with appropriate gas pressures in the chambers provides the ability to tailor the gas plume in a manner that controls the thickness of the material 112 deposited on a substrate.
[0028] “Tailoring”, in accordance with this invention, can be accomplished by: (a) adjusting the gas pressures through the respective conduits 120 ; or (b) adjustably mounting partitions 126 , which are preferably laterally moveable in the plenum, then securing the partitions in place before the nozzle is used; or (c) variably changing gas aperture slit size 151 on modified plate 150 along the length of the nozzle as shown in FIG. 8C; or (d) combinations of (a), (b) and (c) above. In the more preferred embodiment, combinations (a) and (b) are used. Gas pressures are effected via traditional methods common in many industries. The partitions can be effected, for example, by providing each partition or baffle with a set screw (not shown). To adjust one or more of the partitions, face plate 134 is simply removed from housing 122 and the set screws loosened. The partitions are then manually moved laterally in the plenum to locate the partitions relative to the ends of conduits 120 . The set screws are then tightened and face plate 134 returned and secured to the bottom of housing 122 .
[0029] In the special case of depositing molten metal supplied to the upper end (entrance) of channel member 128 , the metal exits the lower elongated opening 131 of the member, is atomized by a continuous curtain of gas flow exiting the continuous aperture 136 , which surrounds the flow of metal from opening 139 , and is deposited on a surface 114 . As best seen in FIGS. 5 and 7, the opening 139 is in the form of one or more longitudinally aligned slits. The opening 139 should be sufficiently large to avoid plugging from metal inclusions or freezing of the metal yet narrow enough to maintain efficient atomization of the metal. In one embodiment, the opening 139 is about 0.015-0.04 inch wide.
[0030] By appropriate partition adjustment, or by knowing and controlling the pressure of the gas flow in conduits 120 , a gas plume 116 a can be provided that does not assume a circle or arcuate configuration before reaching its substrate surface 114 . In this manner, the gas flow remains linear in its movement to the surface, and entrains the liquid material exiting nozzle opening 139 in a linear manner such that a uniform mass of liquid material is laid down on the surface. If the nozzle extends crosswise over a surface, the liquid material is evenly deposited across the width of the surface. If the nozzle and surface are moved relative to one another, either by moving the nozzle, the surface (as in FIG. 6), or both, the deposit of liquid material 112 a is generally deposited evenly crosswise and lengthwise of a surface 114 when relative movement is maintained substantially constant. In FIG. 6, surface 114 is shown as a solid belt that provides a planar surface upon which molten metal can be deposited and solidified to provide a cast metal sheet or plate product 112 a of constant gauge (thickness). The length of the cast product 112 a can be that of the length of belt 114 . Hence “long” sheets of material can be rapidly produced having a desired gauge and width, as determined by the length of opening 139 . Liquid flow rates passing through channel member and the velocity of gas flow through plenum 124 are sufficient to provide a sheet or plate product at rates higher than conventional axisymmetric nozzles.
[0031] Three representative nozzle and partition (or baffle) configurations are shown in accompanying FIGS. 8 a , 8 b and 8 c . In the first of these, FIG. 8 a , partitions 126 are evenly spaced apart. In the second, more preferred embodiment, FIG. 8 b , baffles or partitions 126 are unevenly spaced apart. In FIG. 8 c , the nozzle housing operates at a single gas pressure, P e , with modified plate 150 in place. Within that nozzle configuration, there are no separate chambers but rather side-by-side zones through which varying gas velocities are delivered. Variably sized gas exit slits 151 are shown in plate 150 .
[0032] [0032]FIGS. 9 and 10 show an alternative channel member 228 . Channel member 228 is similar to channel member 128 and includes a first lower neck portion 230 and a second lower neck portion 232 with a nozzle face 234 . The length of the nozzle face 234 determines the width of a sheet produced by the nozzle and may be about 1-80 inches. The width of the nozzle face 234 affects the efficiency of atomization of the liquid; greater widths of the nozzle face 234 reduces atomization efficiency. However, smaller widths render the nozzle face 234 prone to breakage. A preferred width of the nozzle face 234 which avoids these problems when depositing molten metal is about {fraction (3/16)}-¾ inch wide, more preferably ⅜ inch wide.
[0033] The nozzle face 234 defines a linear array of apertures 239 in place of the opening (slits) 139 defined in the channel member 128 . The apertures 239 may be spaced apart regularly or randomly and may be of various sizes and shapes. The configuration of the apertures 239 is determined by selecting a desired liquid flow rate, e.g. the metal deposition rate. The apertures 139 are sized sufficiently large for the material being deposited to avoid plugging by inclusions and freezing or the like, yet provide for uniform distribution of metal over the nozzle face 234 with uniform atomization of the liquid material. For convenience of machining in the nozzle face 234 , the apertures may be circular and spaced equidistant from each other and from the sides and ends of the nozzle face 234 . In a particularly preferred embodiment, the apertures 239 have a diameter D of about 0.08-0.11 inch. The distance S between the center points of each aperture 239 is preferably about twice the distance W between a center point of an aperture 239 and the side of the nozzle face 234 . For nozzle faces longer than about 2 inches, the spacing of the apertures is more critical to the metal deposition profile. For example, spacing the apertures more than 2 inches apart in nozzle faces which are relatively long (e.g. over about 4 inches) will affect the deposit profile. Higher ratios of gas-to-metal flow rates allow for greater distances between the apertures 239 than for lower ratios of gas to metal flow rates. It is also possible to tailor the deposition profile based on the spacing of the apertures 239 as determined by the metal flow rate relative to each 2 inch zone.
[0034] The apertures 239 are less prone to plugging during casting from inclusions in molten metal than the slits 139 which are typically sized 0.02-0.04 inch wide. While freezing of metal passing through the channel member 139 can occur, the apertures 239 are sized to avoid this problem. The nozzle face 234 is readily machined from a variety of materials, including metals and ceramics, and is dimensionally stable due to the bridging effect of the nozzle face material between each aperture 239 . Apertures 239 having a diameter of about 0.08-0.11 inch have been found to produce similar flow and casting results as the slits 139 having a width of 0.02-0.04. The plurality of apertures 239 spaced apart by the distance S provides a uniform curtain of atomized liquid similar to the curtain of gas produced using the channel member 128 .
[0035] The invention described herein has already been tested with water and molten aluminum alloys including 3XXX, 6XXX, 2XXX and 7XXX series (Aluminum Association designations). Such alloys are typically used in the automotive and aerospace industries. On a less preferred basis, this invention can be used to deliver to a substrate a paint, coolant, protective coating and/or irrigant. Representative examples of said materials include: glycol; other molten metals like copper, tin, lead, zinc, iron, nickel and combinations thereof; epoxy-based coatings; vinyl-based coatings, and/or liquid fertilizers. Any of the materials otherwise sprayed in accordance with traditional atomization processes may also be applied through this nozzle configuration.
[0036] Those knowledgeable in the art will recognize other means for accomplishing the main goal of this invention, that being to modulate the gas velocity profile downstream of the nozzle through which atomized materials are passed for eventual substrate deposit. This invention also covers the method of operating nozzle zones at substantially the same pressure, P e , but through differently sized gas slits or openings; or by operating the nozzle at both different pressures and opening sizes.
[0037] Since the exiting gas pressures of this invention are generally greater than atmospheric, these gases expand. This invention exploits the foregoing and thereby actually “tailors” the mass flow of the gas exiting the zones (not necessarily physically partitioned), chambers or physically compartmentalized nozzles.
[0038] Having described the presently preferred embodiments, it is to be understood that the invention may be otherwise embodied by the scope of the claims appended hereto.
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There is claimed a method for depositing fluid material from a linear nozzle in a substantially uniform manner across and along a surface. The method includes directing gaseous medium through said nozzle to provide a gaseous stream at the nozzle exit that entrains fluid material supplied to the nozzle, said gaseous stream being provided with a velocity profile across the nozzle width that compensates for the gaseous medium's tendency to assume an axisymmetric configuration after leaving the nozzle and before reaching the surface. There is also claimed a nozzle divided into respective side-by-side zones, or preferably chambers, through which a gaseous stream can be delivered in various velocity profiles across the width of said nozzle to compensate for the tendency of this gaseous medium to assume an axisymmetric configuration.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The invention concerns the production of sacrificial casting cores for metal casting, in particular sacrificial casting cores of green or fired ceramic, which include metallic reinforcing elements, and their removal from the metallic castings, as well as principal molds for the production of casting cores.
[0003] 2. Related Art of the Invention
[0004] The manufacture of cast parts with recesses or cutouts places high demands on the manufacturing techniques and the materials for the corresponding casting cores. In the field of metallic casting, due to the high temperatures ceramic molds are employed as a rule.
[0005] Slip casting is frequently used in the production of the ceramic casting cores, wherein shaping occurs by pouring liquid slip into a precursor or principal mold. Another frequently seen process is ceramic injection molding, wherein a formable ceramic mass is introduced under pressure into a precursor shape. The slip or ceramic mass is thereupon solidified by drying or, as the case may be, cooling, whereby a green ceramic shape is formed. Particularly in the case of complex shaped casting molds with fine, in part cantilevered or self-supporting structures, there are problems in removal from the mold and problems in the later metallic casting, which are attributable to the insufficient structural stability of the fired and, in particular, the green casting mold.
[0006] Already at the time of removal of the green ceramic out of the principal mold the insufficient stability of the material can lead to breakages of the fine structures. The removal of binder from the green ceramic results in general in a substantial mechanical weakening of the casting mold. In this way, in the case of improperly designed structural geometry, defects or breaking of the fine structure or self-supporting mold parts of the casting can occur.
[0007] A further source of defects during casting can be traced back essentially to the different densities of the ceramic and the casting metals used, in particular the iron alloys or steels. Since the ceramic in general has a substantially lower specific density than the casting metal, the fine and, in part freely projecting parts of the ceramic casting mold tend to float in the molten metal. This leads to geometric shape defects in certain areas of the cast.
[0008] The problem of the insufficient structural stability can in principle be addressed by increasing the sturdiness of the ceramic, for example by ceramic firing (sintering). This however has the serious disadvantage, that the casting mold can only be removed from the cast shape with substantial difficulty following casting. This is the case particularly in the case of casting hollow structures, where the remaining ceramic material is accessible with difficulty.
[0009] Further yet, the sintering of the ceramic generally leads to an unacceptable reduction in porosity.
[0010] Removal of a crust of remaining ceramic material out of the internal space of the castings is disclosed in JP 55097844 A1. This document discloses among other things polymer bound sand casting molds for casting of metal, reinforced with a spiral or helical shaped metal wire. The start and the end of the metal wire project out of the mold core. After the casting of the metal, the metal wire is pulled out of the casting whereupon the core of casting sand is broken up.
SUMMARY OF THE INVENTION
[0011] It is thus the task of the invention to provide geometrically complex casting molds of green or sintered ceramic for metal casting, which exhibit a sufficiently high structural stability to survive the removal from the original mold, as well as to survive metal casting undamaged, and thereupon in simple manner to be released from the casting.
[0012] This task is solved by a sacrificial casting core, which includes at least one metallic reinforcing element, which extends primarily along a longitudinal axis of the casting core, according to the characterizing features of Claim 1 , a process for producing the casting cores according to the characterizing portion of Claim 11 , as well as an original mold for making an impression or molding according to this process having the characteristics of Claim 18 . Preferred embodiments are set forth in the dependent claims.
[0013] In accordance with the invention a sacrificial or lost mold is provided for metallic casting, which is mechanically reinforced using at least one metallic reinforcing element. At least one of the metallic reinforcing elements is a tension spring, which is at least in proximity to the surface of the casting core, or in certain cases, near to the core marks. The melting point of the spring or the metallic reinforcing element is preferably at least equal to that of the casting metal.
[0014] The term “casting core” is understood herein to refer to a structure contained in a casting mold or a shape which is in greatest part surrounded by flowing casting metal. The casting core can be completely integrated into the casting mold, or only be loosely laid therein. Included in the term “casting core” in the sense in the present invention are those structures which produce a hollow space in the casting body.
[0015] In accordance with the invention, one or more metallic reinforcing elements can be contained within the casting core, wherein the casting core itself is comprised of green or fired ceramic. Preferably the casting core essentially contains one metallic reinforcing element, or multiple elements which are connected with each other. The reinforcing effect is, as a rule, higher in the case of green ceramics than in the case of fired ceramics.
[0016] With regard to their composition the casting cores can be of the same or of a different material than the rest of the casting mold. Thus, for example, the combination of casting core of green ceramic and a casting mold of fired ceramic or granular molding material (sand) are of particular interest.
[0017] The metallic reinforcing element brings about herein, in accordance with the invention, an increase in the structural stability in the fine or mechanically highly stressed areas of the casting mold, as well as in the extended self-supporting areas.
[0018] The reinforcing effect is substantial in particular in the case of the green ceramic. However, the sturdiness of the metallic reinforcing element is overall generally above that of the ceramic material also in the case of sintered ceramic, since the casting mold is not fired to a solid and tight ceramic. The increase of the sturdiness imparted by the metallic reinforcing element corresponds herein at least to that amount necessary for undamaged removal of the green ceramic casting core out of the original mold or for undamaged metal casting. Since the metallic reinforcing element remains in the casting core also during the metal casting process, it is advantageous to select the melting temperature of the metallic reinforcing element such that it is above the casting temperature. At least the melting temperature of the reinforcing element should lie above the melting temperature of the casting metal.
[0019] For this reason the preferred materials of the metallic reinforcing element include Fe- or Ni-alloys and steels. Further suitable metals are Ti-, W-, Nb- or Ta-alloys.
[0020] At least one reinforcing element is preferably oriented along one of the longitudinal axis of the casting mold, particularly in the area of the fine and in part self-supporting structures.
[0021] At least one reinforcing element is, in accordance with the invention, a tension spring. In the sense of the invention a tension spring is understood to be a mechanical element with the characteristics of elastically deforming in response to external forces and which, upon release of external forces, returns to the original shape by springing back. This effect can be imparted in the case of springs in this field by the selection of high elastic materials and by suitable design. The most common material for this type of spring is steel.
[0022] The inventive reinforcing elements in the form of a tension spring include spiral springs as well as plate springs, a ring disk in wedge shaped tensioned in the axial direction, which can be combined with additional plate-springs into spring packets (in the case of like-oriented stratification) or spring columns (in the case of alternating arrangement).
[0023] One preferred embodiment of the tension spring is a screw thread shaped spring, for example produced from round wire in the form of a draw spring or pressure spring, which has a circular diameter. In a first embodiment of the invention the casting core is comprised of a green ceramic which surrounds the metallic reinforcing element. The green ceramic is essentially comprised of ceramic material and organic binder in an amount of 0.1 to 8 wt. %.
[0024] The preferred ceramic materials include refractory oxides, in particular the oxides and/or mixed oxides of the elements Al, Zr, Si, Mg, Ca or Ti, or refractory carbides or nitrides of the elements Si and/or Ti. Particularly preferred are ZrSiO 4 , Al 2 O 3 , SiC and/or ZrO 2 .
[0025] Among the ceramic binders, preferred are those suitable for freeze-drying processes. These include in particular gelatins, agaragar or agarose and glycerin.
[0026] It has surprisingly been found that the inventive reinforced casting cores of green ceramic can also be employed in casting molds for metal casting without ceramic firing. By this procedure the process step of ceramic firing can be omitted. It is however of particular advantage that the shrinkage (sinter shrinkage) brought about by ceramic firing is substantially reduced. Here only the thermal decomposition of the organic binders and the shrinkage of the casting core caused by the short exposure to the casting temperature occur. The low stability of the ceramic materials produced hereby are increased by the inventive metallic reinforcing element. The small shrinkage of the casting core has a very positive effect on the dimensional stability of the casting. The green casting cores can thus be components of a casting mold of fired ceramic as well as of green ceramic.
[0027] In a further embodiment of the invention the casting core which surrounds the metallic reinforcing element is fired ceramic. The preferred ceramic materials are the same as discussed above for the green core. The fired ceramic therein typically exhibits a porosity of greater than about 5%.
[0028] The preferred tension springs include the springs made of round wire wound into spiral or helical shapes and tension springs with high spring constants and those of steels.
[0029] A particular advantage of the inventive metallic reinforcing elements is based on their design as tension springs. Following casting, the tension spring can be pulled out of the cast part or casting, whereby the casting core is mechanically stressed internally. As a rule the ceramic material under this mechanical stress suffers brittle fractures and breaks into small pieces. These small pieces fall out of the casting in part as loose pieces, or can be removed in simple manner by particle blasting techniques such as sand blasting or water impacting techniques.
[0030] In a further inventive embodiment of the invention at least one of the metallic reinforcing elements is partially or entirely separated from the surrounding casting core. In the case of the ceramic casting core the separation is a gap or cleft.
[0031] In the case that the casting core of grain ceramic the partial or full separation inventively occurs using pyrolyzable organic material. Therein it is to be noted that the organic material decomposes at least in part upon ceramic firing or at least upon the preheating to the casting temperature, and thereby produces essentially the same situation as in the case of ceramic casting cores which exhibit a gap. Among pyrolyzable organic materials, waxes or thermal plastics are, for example, well suited.
[0032] In a further inventive variation, this separation is caused by a flexible and compressible hose, which is comprised at least in part of a pyrolyzable material. Examples therefore are silicon hoses, as well as polymer or wax impregnated fiberglass or carbon fiber webbed hoses.
[0033] The gap can preferably function as a ventilation or evacuation channel or a riser. The ventilation channel therein brings about an improved decomposition and degassing of the organic binders of the green ceramic during firing. The gap breadth is typically less than 2 cm and preferably in the range of 0.02 to 2 mm.
[0034] The gaps formed around the tension spring or as the case may be the reinforcing element can therein further improve the mechanical disruption of the ceramic during pulling out, in that they afford some play or a gap for the back and forth movement of the reinforcing element.
[0035] The inventive sacrificial or destructible casting core is suitable in particular for production of casting parts with hollow spaces, recesses or cavities. Preferred areas of use are components for internal combustion engines or steels or like metals, in particular engine blocks. Particularly preferred are ceramic casting molds with casting cores of green ceramic.
[0036] A further aspect of the invention concerns a process for production of reinforced sacrificial casting cores for metal casting.
BRIEF DESCRIPTION OF THE DRAWINGS
[0037] In the following the invention will be described in greater detail on the basis of schematic illustrations. The illustrations are to be understood as merely being examples and are not to be construed as limiting the scope of the invention.
[0038] Therein there is shown:
[0039] FIG. 1 a principal or original mold ( 4 ) of multiple segments ( 1 ), a flexible internal mold ( 2 ), which includes cutbacks ( 3 ), anchoring nubs ( 5 ), a mold cavity ( 6 ) and filler necks ( 7 )
[0040] FIG. 2 a principal mold ( 4 ) filled with ceramic slip ( 9 ), with metallic reinforcing elements ( 8 ), namely tension spring ( 10 ) and metal wire ( 12 )
[0041] FIG. 3 a partially opened principal mold with a casting core ( 17 ) of frozen ceramic slip ( 13 ) and embedded metallic reinforcing elements ( 8 )
[0042] FIG. 4 an assembled casting mold ( 14 ) with a metal reinforced frozen casting core ( 13 ), with a tension spring ( 10 ) and a casting cavity ( 15 ).
DETAILED DESCRIPTION OF THE INVENTION
[0043] In accordance with the invention, the process includes the following steps
preparing an original mold ( 4 ), wherein the original mold can include multiple segments ( 1 ) as well flexible internal molds ( 2 ) fitting at least one elastically deformable metallic reinforcing element ( 8 ), including at least one tension spring ( 10 ), into the original mold ( 4 ) filling the original mold ( 4 ) with ceramic slip ( 9 ) drying and thereby forming a dried ceramic slip ( 13 ) or, as the case may be, green ceramic in the form of a casting core ( 17 ) removal of the casting core ( 17 ) out of the original mold.
[0049] The principal mold can be made of almost any hard material, for example plastic, ceramic or metal. The principal mold is preferably made of metal.
[0050] Preferably the principal mold is made of multiple separable segments ( 1 ).
[0051] In a preferred embodiment of the principal mold, one or more flexible internal molds or liner ( 2 ) are contained therein. These internal molds are for example made of rubber or silicon. Particularly preferred is to have the internal molds connected with the principal mold via connecting techniques for example via nubs for fixation (fixing nubs ( 5 )). The inner molds of flexible material typically exhibit cutbacks ( 3 ) and/or complex geometries. The principle mold or form, which can be comprised of multiple parts, corresponds to the general shape of the principal model, essentially without cutbacks and complex geometries. For filling the principal mold, filler necks ( 7 ) can be provided. After freezing of the slip the flexible internal mold or liner can be pulled from the frozen ceramic part in order to allow for drying of the component in a freeze-dryer.
[0052] At least one reinforcing element ( 8 ) is seated in the principal mold, wherein at least one of these is a tension spring ( 10 ). One or more reinforcing elements can therein also be built up of multiple individual elements. For example, the reinforcing element can be a metal wire ( 12 ) and a tension spring ( 10 ) associated therewith. Further embodiments of the reinforcing element include for example corrugated sheets, spiral or helical wires or plate springs.
[0053] Preferably at least one of the metallic reinforcing elements is oriented along the longitudinal axis of the casting core.
[0054] Preferably at least one of the metallic reinforcing elements is so fitted or seated, that at least one of its ends lies near to the surface of the casting core or projects out therefrom. This one end of the metallic reinforcing element is therein at least so close to the surface that following the casting process it is easily accessible and allows itself, upon application of external force, to stretch and be pulled out of the casting core.
[0055] In a further embodiment of the invention at least one of the reinforcing elements is coated with pyrolyzable material or is surrounded by a hose, in particular a ventilation (off gassing) hose. Therein the hose is likewise at least pyrolyzable in part. The term pyrolysis is herein understood to be the partial or complete thermal decomposition of the material. The coating or the (off gassing) hose can act as a buffer during the drying of the slip, as well as during sintering of the green ceramic, for the shrinkage processes which occur, since the corresponding material of the coating or hose is relatively soft. In particular the direct shrinkage and contact-rubbing of the green or sintered ceramic on the metallic reinforcing element is prevented.
[0056] The coating or the off gassing hose provides a further advantage for the removal of the reinforcing element from out of the cast shape following casting. Since the coating or the off gassing hose decomposes at least in part pyrolytically prior to or at the casting temperature, a gap is formed during casting, which can act as an off-gassing channel. The gap beyond this facilitates the removal of the reinforcing element and the breaking up of the ceramic casting core. The coating can be made for example of waxes or thermal plastics.
[0057] A further embodiment of the invention includes hollow metallic reinforcing elements, for example pipes or hollow helices or spirals. The hollow spaces exhibit a similar effect to that of the gaps between reinforcing element and casting core material.
[0058] Following the seating of the metallic reinforcing element and the, in some cases, further metallic elements, the filling of the principal mold with ceramic slip occurs. The slip in general comprises powders of refractive oxides or carbides, binders and solvents.
[0059] The particularly preferred slips include aqueous slips. The particularly preferred binders include those suitable for freeze-drying processes, for example gelatins, agaragar, glycerin and agarose.
[0060] In a subsequent process step the drying or, as the case may be, solidification of the slip and the removal of the solvent occurs.
[0061] In accordance with the invention the drying process is so selected that a minimum of shrinkage of the slip occurs during drying.
[0062] The particularly preferred processes include freeze-drying. Herein only a minimum of shrinkage results. By the drying of the ceramic slip a green ceramic is formed in the shape of the later casting core.
[0063] The casting core is thereupon removed from the principal mold. As a result of the inventive reinforcing elements the casting core possess sufficiently sturdiness, even in the case of complex geometries, high porosity or green ceramic, and even in the case of a low binder content. Even long and thin casting cores can, in accordance with the invention, be removed without problem. As binder, even minimal amounts in the range of a few percent can be sufficient. Preferred slip compositions have a gelatin content of less than 3 wt. %.
[0064] The flexible inner shapes or liners ( 2 ) can, in certain, cases be reused.
[0065] For the production of cast parts the casting core is used as a complete casting mold or as a part of a casting mold. Therein the casting core can be used in the green form or in the sintered form.
[0066] A preferred embodiment of the invention envisions the assembly of multipart cast molds such as shown for example in FIG. 4 . Therein the casting core ( 13 ), as well as the casting mold ( 14 ) can be of green ceramic or a sintered ceramic. If green and sintered ceramics are to be employed simultaneously, then the casting mold ( 14 ) is preferably of sintered material and the casting core of green material. The casting mold ( 14 ) can therein be provided with reinforcing elements in the same or similar manner as the inventive casting core.
[0067] With regard to the ceramic casting core, these are sacrificial or lost cores which, following the casting of the metal, are destroyed by the pulling out of at least one of the metallic reinforcing elements.
[0068] The ceramic broken up thereby can be removed from the cast shape with comparably little effort. In particular, particle blasting or water blasting can be employed in order to remove the broken pieces and residue of ceramic out of the cast shape.
[0069] The inventive reinforcing elements have the advantage that they can be used for large surface area breaking up of the reinforced casting core, and therewith substantially simplify the removal of the cast part from the mold.
EXAMPLE
[0070] First a prototype of the casting core was produced of plastic. This occurred by a generative rapid prototyping process. Thereupon a principal mold generally defining the geometry of the prototype model was formed of multiple segments ( 1 ) of polyurethane. The intermediate spaces between the prototype model and the principle mold were cast-in with a thin liquid silicon mass which, following hardening, formed a flexible internal mold or liner ( 2 ) with cutbacks ( 3 ).
[0071] Into this principle mold a metal wire surrounded by a tension spring was seated. Tension spring and metal wire were comprised of spring steel.
[0072] The mold was preheated and the hot slip was cast into the mold without pressure.
[0073] This slip was produced in the following manner:
[0074] At 60° C. a concentrated solution having 25 wt. % gelatin was produced in order to be mixed in a later process at a temperature of approximately 50° C. with the ceramic suspension.
[0075] For production of the ceramic suspension, ZrO 2 , ZrSiO 4 and SiO 2 -powder were mixed and dispersed in water for 1 hour at average rotational speed in a plastic grinding container using Al 2 O 3 grinding balls in a planetary grinding mill. Thereupon the gelatin solution was added and mixed for an additional 30 minutes.
[0076] The slip produced in this manner had a gelatin content of 3.7 wt. % and a solids content of 60 wt. %.
[0077] Thereupon the grinding balls were removed and the slip was cooled to a temperature of approximately 40-45° and cast into the principle mold with flexible inner shapes. Thereupon the gelatin was slowly cooled to below the gelation temperature (approximately 35° C.) and the entire mold was frozen in a cooler to −30° C. Thereupon the principle mold was removed or, as the case may be, the flexible inner liner was released. For handling purposes, the frozen slip was maintained at a temperature below approximately −10° C. An intermediate storage of the casting core at approximately −2° C. was possible without occurrence of damage.
[0078] The casting core of frozen slip was thereupon freeze-dried at a temperature of approximately −30° C. and a pressure in the vicinity of 1-100 Pa. The freeze-dried component was thereupon subjected to a further drying at 60° C. in a drying cabinet.
[0079] The green casting core was introduced into a ceramic casting mold and used for casting of molten steel. The principle design of the casting core corresponded to that of FIG. 4 .
[0080] Following casting, the ceramic casting core was removed and the tension spring of the casting core, which was virtually completely surrounded by casting metal, was exposed at two opposite ends. By pulling of the ends of the tension spring the casting core was broken up into small and loose broken pieces and could be completely removed by a water jet.
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Sacrificial lost casting cores of green or fired ceramic, which include at least one tension spring as a metallic reinforcing element, wherein at least one end of this reinforcing element lies near one of the surfaces of the casting core or extends therethrough, and wherein the melting point of all metallic reinforcing elements lie above the melting point of the casting metal, as well as processes for production of such casting cores, including the steps of preparing a principal mold, seating therein at least one reinforcing element, filling the principal mold with ceramic slip, drying the slip for formation of a green ceramic and releasing the casting core from the principal mold. The principal mold is preferably lined with a flexible internal mold or liner. The reinforcing element in the form a tension spring can be used following casting for breaking up the ceramic casting core.
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FIELD OF INVENTION
The present invention relates to continuous inkjet (CIJ) printers and, more particularly, to CIJ printers of the multi-nozzle type.
BACKGROUND ON THE INVENTION
Multi-nozzle continuous inkjet printers have been developed in order to provide high quality, high speed printing. A row of inkjet nozzles at very close spacings are provided and individual streams of ink issue from each of the nozzles continuously in use, being broken up into individual droplets automatically. The individual droplets are charged appropriately to cause them to be printed or else deflected into a gutter. Printers of this type are described, for example, in U.S. Pat. Nos. 4,613,871 and 4,427,986. the printers described in these specifications are of the type generally known as binary continuous multi-jet.
In order to control the printing process accurately, it is known to detect both the velocity of the droplets being emitted from the droplet generator nozzles and to determine the phase of droplet charging with respect to droplet generation by means of electrodes which extend transverse to the path of the droplets.
The phase detection and velocity detection electrodes, as they are known, can be disposed between the charge electrodes and the deflection electrode or electrodes. However, it is important to ensure that, for accuracy of phase and velocity detection, the phase and velocity detector electrodes are themselves very accurately positioned with respect to the charge electrode.
SUMMARY OF THE INVENTION
The present invention is aimed at ensuring accurate location of the phase detector and/or velocity detector electrodes in a continuous inkjet printer.
According to the present invention a multi-jet CIJ printer has a deflection electrode having a window formed therein, a phase detector or velocity detector electrode being disposed within the window.
Preferably, when forming a pair of detectors within the envelope of the deflection electrode, the phase detector and velocity detector electrode are formed, by a deposition process in which a non-conductive dielectric plate, preferably formed of alumina, is pre-drilled with a pair of holes spaced apart on the surface of the plate and a conductive material, for example, gold, silver or other suitable conductive metal or composite is plated through the holes. Thereafter, one side of the dielectric plate is plated with a conductive layer which is not connected with the plating through the holes, the interior of the holes being filled through with a dielectric material such as glass to create a liquid tight barrier, and a pair of dielectric layers, one corresponding to each of the detectors, are laid down, each of the dielectric layers surrounding a respective one of the holes through the plate. On top of these dielectric layers the detectors are plated, for example, using gold, silver or other suitable conductive material, each of the conductive layers forming the detectors being connected to the conductive plating through the respective hole. Further dielectric layers are laid over the detectors and then the face of the plate is plated with a conductive material, to provide the deflection electrode, with a pair of windows being left above each of the detector areas before the detector areas are partly exposed within the windows.
On the other face of the dielectric plate a pair of conductive connector pads may be formed in communication with the plated conductive layers through the holes and a conductive screen layer is plated onto the dielectric substrate around, but not in contact, with the conductive pads. A dielectric covering layer is then printed over the conductive layer with a pair of small windows being left at the location of each of the conductive pads, one window of each pair being positioned directly over the conductive pad and the other spaced from it so as to lie over the conductive screen layer. This enables connection of the inner core to the respective detector and the shield layer of a coaxial conductor to the shield (deflection electrode), with the conductor lying substantially parallel to the face of the plate.
Locating the phase detector and/or velocity detector electrode or electrodes within the face of the deflection electrode not only achieves a compact design, but also, since the deflection electrode is located accurately with respect to the charge electrodes, achieves corresponding accuracy of location of the phase detector and/or velocity detector electrodes with respect to the charge electrodes.
BRIEF DESCRIPTION OF THE DRAWINGS
One example of a deflection electrode with phase detector and velocity detector electrodes formed in the face thereof will now be described with reference to the accompanying drawings in which:
FIG. 1 is a side view of the print head of a multi-nozzle CIJ printer as described in our EP-A-0780231; and,
FIGS. 2 to 8 illustrate various stages in the manufacture of the integrated phase detector and velocity detector electrodes.
DETAILED DESCRIPTION OF THE INVENTION
The printhead shown in FIG. 1 is described in more detail in our EP-A-0780231. Since not all the features shown in FIG. 1 are relevant for a description of the present invention only the primary features will be referenced and described.
The printhead has an electronics sub-system 1 by means of which are controlled the piezoelectric oscillator 2 forming part of a droplet generator 3 which has a nozzle plate 4 from which, in use, issue plural streams 5 of ink. The closely spaced nozzles are arranged in a row normal to the plane of the drawing. The streams of ink break up into individual droplets which pass respective charge electrodes 6 also arranged in a row in the same direction, where they are selectively charged and then passed between a pair of deflection electrodes 7 , 7 ′ which establish, in use, an electric field by means of which charged droplets are deflected from their straight-line path into a gutter 8 . Formed in the face of the deflection electrode 7 are a phase detector electrode and velocity detector electrode (neither of which is shown in FIG. 1) which are used to detect the charge applied to droplets by the charge electrode 6 and the speed of the droplets respectively.
FIGS. 2 to 8 illustrate the phase detector electrode and velocity detector electrode and their manufacture in more detail.
The phase detector 9 and the velocity detector electrode 10 are formed, together with the deflection electrode 7 , by a deposition process, in which, as a first step (see FIG. 2) a non-conductive rectangular dielectric plate 11 , preferably formed of alumina and pre-drilled with a pair of holes 12 spaced apart on the surface of the plate, has a conductive material 13 , for example, gold, silver or other suitable conductive metal or composite, plated through the holes 12 . Thereafter (also FIG. 2 ), one side of the dielectric plate 11 is screen printed or otherwise plated with a conductive layer 14 which provides a shield in use, and which is not connected with the plating 13 through the holes. The interior of the holes is then filled through with a dielectric material 15 such as glass to seal them against liquid.
Next (see FIG. 3 ), on top of the conductive layer 14 , a pair of dielectric layers 16 , one corresponding to each of the detectors, are laid down, each of the dielectric layers surrounding a respective one of the holes 12 through the plate 11 . On top of these dielectric layers 16 , the detectors 9 , 10 are then screen printed or otherwise plated (see FIG. 4 ), for example, using gold, silver or other suitable conductive material, each of the conductive layers forming the detectors 9 , 10 being connected to the conductive plating 13 through the respective hole 12 .
Further dielectric layers 17 are then (see FIG. 5) laid down over the detectors, and then (see FIG. 6) the major part of the face of the plate is plated with a conductive material 18 , with a pair of “windows” 19 , 20 being left above each of the detector areas 9 , 10 before the detector areas are partly exposed within the “windows”.
On the other face of the dielectric plate 11 (see FIG. 7) a pair of conductive connector pads 21 , 22 are formed in communication with the plated conductive layers 13 through the holes 12 and a further conductive screen layer 23 is plated onto the dielectric substrate around, but not in contact with, the conductive pads 21 , 22 . A dielectric covering layer 24 is then printed over the conductive layer 23 with a pair of small windows 24 , 25 being left at the location of each of the conductive pads 21 , 22 , one window 24 of each pair being positioned directly over the conductive pad 21 , 22 and the other pad spaced from it so as to lie over the conductive screen layer 23 . This enables connection of the inner core and the shield layer respectively of a coaxial conductor (not shown) to be made to the conductive pad 21 , 22 and shield 23 respectively, with the conductor lying substantially parallel to the face of the plate. This provides a secure shielded connection to each of the detectors 9 , 10 in a simple manner which does not occupy significant space on the side of the deflector plate opposite the detectors 7 , 9 , 10 .
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E1 A CIJ printhead includes a droplet deflector electrode having one or more windows formed therein, and a phase or velocity detector electrode disposed within the window. A method of forming the electrodes by plating multiple conductive and dielectric layers is also disclosed.
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BACKGROUND OF THE INVENTION
The present invention relates to a Ti alloy poppet valve which provides improved wear resistance and strength, and surface treatment thereof.
The largest difficulty for increasing allowable rotation speed of an engine is increase in inertial mass owing to increase in weight of valve-operating parts. If whole weight of the valve-operating parts increases, followability of a valve body to a cam decreases owing to inertial mass during high-speed rotation so as to decrease engine output performance.
Therefore, a poppet valve is molded from a low-density heat resistant Ti alloy to decrease its weight instead of a conventional heat resistant steel. However, Ti alloy has activity and is likely to adhere to another metal. Wear resistance and fatigue strength are not sufficient. Surface treatment such as nitriding and Ni plating is made on the surface of Ti alloy valve to improve wear resistance.
The nitrided valve provide high strength or hardness and wear resistance, but it is too rigid, so that it is likely to attack other parts. It is required to replace material of another valve-operating member which contacts the valve to increase manufacturing cost. A Ni plated valve does not achieve sufficient heat resistance and is not suitable as an exhaust valve.
SUMMARY OF THE INVENTION
In view of the disadvantages, it is a primary object of the present invention to provide a Ti alloy poppet valve which improves wear resistance and strength without nitriding or plating.
It is another object of the invention to provide a method of surface treatment of the poppet valve.
BRIEF DESCRIPTION OF THE DRAWINGS
The features and advantages of the invention will become more apparent from the following description with respect to embodiments as shown in attached drawings wherein:
FIG. 1 is a central vertical sectioned front view of a poppet valve according to the present invention;
FIG. 2 is a front elevational view of a wear tester; and
FIG. 3 is a graph which shows the results a test.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
FIG. 1 illustrates a Ti alloy poppet valve. A valve body 3 which comprises a valve stem 1 and a valve head 2 at the lower end is molded from Ti--Al alloy such as a phase Ti--5Al--2.5Sn alloy, (α+β) phase Ti--6A1--4V alloy or Ti--6Al--2Sn--4Zr--2Mo alloy made of (α+β) phase which contains a small amount or less than 10% β phase (Near α).
An oxidized layer 4 which contains TiO 2 and has thickness of 10 to 15 μm is formed on the surface of parts which requires high wear resistance and fatigue strength, such as a valve face 5 which contacts a valve seat, an intermediate part 6 of the valve stem 1 which is slidably engaged in a valve guide, an annular groove 7 on which a cotter is engaged, and an end face 8 on which a rocker arm or a tappet is engaged. A boundary layer 4a between the oxidized layer 4 and the valve body 3 has needle crystal structure.
The oxidized layer 4 is formed by heating the surface of the propane and a natural gas to a predetermined temperature to oxidize the surface layer. The oxidized layer 4 may be formed by a high frequency induction heater.
After the oxidized layer 4 is formed, a carburized layer 9 which contains Ti and has thickness of 3 to 5 μm is formed by carburizing on the whole surface of the valve body 3. The carburized layer 9 is formed by heating the surface of the valve body 3 at temperature of less than transformation point such as 800° C. by a high density energy heater such as plasma, laser and electronic beam and diffusing carbons by gas carburizing.
The high density energy heater such as plasma locally heats only the surface for a short time to prevent heat from transferring to the inside, thereby preventing changing of the material of the valve body 3 not to decrease fatigue strength. It is also advantageous in reducing carburizing time.
The carburized layer 9 may be formed, and then the oxidized layer 4 may be formed therein. In this case, oxidization is carried out by an acetylene gas to diffuse carbons in the gas into the material, thereby promoting in the oxidization step.
As carried out by the foregoing embodiment, the valve body 3 is made of Ti--Al alloy, or α phase, (α+β) phase or (α+β) phase which contains a small amount of β phase and the carburized layer 9 is formed on the surface, so that the valve body 3 is strengthened with advantage of equiaxed structure of the valve body 3 to increase tension ductility and fatigue strength. By forming only the carburized layer 9, fatigue strength is increased by about 20%.
Furthermore, the oxidized layer 4 is formed in the parts of the valve face 5 which contacts another valve-operating member, and the boundary layer 9a therebelow is partially organized to a needle crystal structure, thereby increasing wear resistance and toughness of the surface layer significantly without decreasing fatigue strength of the whole valve body 3.
The oxidized layer 9 is not too rigid as compared with a conventional nitriding, so that aggressiveness to another valve-operating member does not increase.
The inventors makes samples the surface of which was treated and a wear test is carried out to the samples. A wear tester and how to examine will be described.
FIG. 2 illustrates a Crossbar tester which comprises a motor 10, a sample fixing jig 11 which moves up and down just above the end of a shaft 10a of the motor 10 and a weight 12 on the fixing jig 11.
At the end of the shaft 10a, a disc-shaped steel chip 13 which is ground at the outer circumferential surface and treated with oil extraction is concentrically mounted. Then, on the lower surface of the fixing jig 11, a sample 14 which is treated with oil extraction and has a flat lower end face is mounted, and the lower end face is engaged on the upper surface of the chip 13. A 1 kg weight 12 is put on the upper surface of a fixing jig 11, and a motor 10 is operated to rotate the chip 13 at fixed speed. A weight is added by 500 g every time the chip 13 slides on the sample 14 by 50 m which is determined by rotation of the motor and an outer diameter of the chip.
The test is finished when seizure and galling occurs between the sample 14 and the chip 13 or when sliding distance reaches to 350 m.
The results of the test are shown in FIG. 3. The sample "A" denotes an ordinary Ti--Al alloy which is not hardened on the surface; "B" denotes Ti--6Al--4V alloy on which a carburized layer is formed; "C" denotes Ti--6Al--2Sn--4Zr--2Mo alloy on which a carburized layer is formed; "D" denotes one which has further an oxidized layer in "B"; and "E" denotes one which has further an oxidized layer in "C."
As shown in FIG. 3, in seizure occurrence distance, the samples "B" and "C" which have only carburized layer is better than non-hardened sample "A", and the samples "D" and "E" which have oxidized layer on the samples "B" and "C" are greatly better. Especially, the sample "E", Ti--6Al--2Sn--4Zr--2Mo, has no seizure even if it slides by 350 m, to provide significant high wear resistance.
As described above, in the present invention, the oxidized layer 4 is formed only on parts which are engaged with another valve-operating member to form needle crystal structure, and the carburized layer 9 is formed on the whole surface of the valve body 3 to improve wear resistance and fatigue strength totally. Thus, without decreasing fatigue strength of the valve body 3 itself, wear resistance and toughness of the surface layer can be improved.
It is considered that the valve body 3 is directly oxidized on the surface, but it is difficult to obtain the above oxidized layer owing to reflection rate of the surface, and treatment time must be extended. Thus, heated area increases, and needle crystal structure increases to decrease fatigue strength of the valve body.
Before oxidization, a carbon spray film used in a laser beam processing may be applied to the surface of the valve body 3. So formed even if the carburized layer 9 is thin.
The present invention is not limited to the foregoing embodiments. In the foregoing embodiment, the oxidized layer 4 is formed on part which contacts another valve-operating member and the lower boundary layer 4a is formed as needle crystal structure. But only the oxidized layer 4 may be formed without such needle crystal structure.
In the foregoing embodiments, the valve body 3 is made of Ti alloy which comprises α phase, (α+β) phase, or (α+β) phase which contains a little amount of β phase, but Ti alloy which comprises β phase may be used.
Various modifications and changes may be made by person skilled in the art without departing from the scope of claims wherein:
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A poppet valve in an internal combustion engine of a vehicle consists of a valve body which comprises a valve stem and a valve head at one end of the valve stem. An oxidized layer is formed on portions of the valve body which contacts another valve-operating member. On the oxidized layer, a carburized layer is formed to cover the whole surface to increase wear resistance and fatigue strength of the valve.
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FIELD OF THE INVENTION
The present invention relates to a method for driving the driving device of head light of vehicles, especially for a method for detecting errors and correcting the positions of the head light to pre-set positions.
BACKGROUND OF THE INVENTION
One of the latest safety devices for vehicles is the Adaptive Front-lighting System (AFS) which allows the head light turns according to needs and the system includes a driving device to turn the head light. A latest driving device known to applicant includes step motor and a sensor connected to the output shaft of the motor, wherein the sensor detects the angle that the output shaft rotates and generates a reference voltage which is compared with a pre-set voltage so as to decide the position of the head light. A control unit is then activate the step motor to rotate the output shaft of the step motor to move the head light to pre-set position. Although errors from the parts or the environment have been considered by the known device, the range of the pre-set voltage does not include method for detecting errors. Therefore, the drivers cannot correct the movement of the head light when errors that are not considered by the device happen. In other words, if the driving device of the head light cannot work functionally and the driving device cannot correct the errors, the drivers take risks to drive.
The present invention intends to provide a method for driving the driving device of the head light and the method provides a detection function to detect errors of the movement of the head light.
SUMMARY OF THE INVENTION
The present invention relates to a method for detecting errors in driving device of head light of vehicles, and the method includes the following steps:
step 1: activating driving device of head light and a main circuit beginning to operate;
step 2: initializing a microprocessor control unit of the main circuit and zeroing the counting condition, the microprocessor control unit detecting parts in the main circuit and making judgement of error;
step 3: judging whether position of driving shaft is detected, if the position of the driving shaft is not detected, a motor being activated to rotate the driving shaft and the counting condition being added by one and stored as record, judging whether the number of the counting condition is over three, if the number of the counting condition is less than three, repeat step 3, if the number is over three, an error judgement is made and the main circuit is stopped;
step 4: the microprocessor control unit obtaining pre-set position and recording the position, the microprocessor control unit obtaining current position of the driving shaft, the pre-set position and the current position being compared, if the result of comparison is different, the motor driving the driving shaft to the pre-set position;
step 5: judging whether the driving shaft is returned to the pre-set position, if the driving shaft is not returned to the pre-set position, the counting condition is added by one and stored as record, judging whether the number of the counting condition is over pre-set times, if the number of the counting condition is less than the pre-set times, repeat steps 3 to 5, if the number is over the pre-set times, an error judgement is made and the main circuit is stopped;
step 6: judging whether the revolution of the motor is in a range of restriction, if the revolution of the motor exceeds the range of restriction, the counting condition is added by one and stored as record, judging whether the number of counting condition is over five, if the number is less than five, repeat steps 2 to 5, if the number is over the pre-set times, an error judgement is made and the main circuit is stopped, and
step 7: when completing steps 1 to 6, a driving module of the driving device is set and the driving device is ready to active, the driving device is ready to accept commands from the microprocessor control unit, the main circuit is stopped.
The primary object of the present invention is to provide a method to detect the current position of the head light and the method is able to judge the status of the head light during driving.
The present invention will become more obvious from the following description when taken in connection with the accompanying drawings which show, for purposes of illustration only, a preferred embodiment in accordance with the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a perspective view of the driving device of head light of the present invention;
FIG. 2 is an exploded view of the driving device of head light of the present invention;
FIG. 3 is a plane view to show that the reduction gear set is engaged with a rack on the driving member;
FIG. 4 is an exploded view of another embodiment of the driving device of head light of the present invention;
FIG. 5 shows a flow chart of the main circuit of the present invention;
FIG. 6 shows a first method for detecting the current position of the head light;
FIG. 7 shows a second method for detecting the current position of the head light;
FIG. 8 shows a third method for detecting the current position of the head light;
FIG. 9 shows the flow chart to illustrate that the driving shaft is moved back to original position.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIGS. 1 to 3 , the driving device for head light of the present invention comprises a box 1 , a motor 2 , a reduction device 3 , a driving member 4 , a circuit board 5 and a driving shaft 6 . The box 1 includes a base 11 and a top board 12 , wherein the base 11 has a first hole 111 through which the output shaft 21 of the motor 2 extends and a second hole 112 through which the driving shaft 6 extends. The reduction device 3 , the driving member 4 and the circuit board 5 are received between the top board 12 and the base 11 .
The output shaft 21 has a gear 22 which is engaged with one of the gears of the reduction device 3 and the motor 2 is connected to an underside of the base 11 . Therefore, when the output shaft 21 rotates, the reduction device 3 is activated.
The driving member 4 has a fan-shaped rack 41 which is engaged with the reduction device 3 so that the driving member 4 is driven by the reduction device 3 when the motor 2 is activated. A magnet with N pole and S pole is received in one end of the driving member 4 and faces the circuit board 5 . The other end of the driving member 4 is connected with the extension 61 of the driving shaft 6 . The circuit board 5 has a microprocessor control unit (MCU) and a detection circuit composed of a sensor which is located corresponding to the magnet 42 so that when the driving member 4 rotates, the sensor 51 senses the change of magnetic field and generates a reference number which is sent to the MCU.
When in assembling, the extension 61 of the driving shaft 6 extends through the second hole 112 and is connected to the second end of the driving member 4 . The reduction device 3 is then installed in the base 11 and engaged with the gear 22 on the output shaft 21 of the motor 2 and the rack 41 of the driving member 4 . The circuit board 5 is installed to the bas 11 and the top board 12 is then mounted to the base 11 .
The driving shaft 6 is connected to the head light (not shown) and when the driving member 4 rotates, the sensor of the detection circuit senses the change of magnetic field due to the movement of the magnet 42 in the driving member 4 . The change generates a reference number and sent to the MCU to judge the current position of the driving shaft 6 . The current position is compared with a pre-set position, if the two positions are different, the motor 2 drives the reduction device 3 to rotate the driving shaft 6 to the pre-set position.
FIG. 4 shows another embodiment of the driving device, wherein the driving member 7 has a fan-shaped rack 71 which is engaged with the reduction device 3 . A hole 72 is defined in an end of the driving member 7 and faces the circuit board 5 . The other end of the driving member 7 is connected to the driving shaft 6 . The circuit board 5 has a detection circuit composed of a variable resistance 8 which is engaged with the hole 72 of the driving member 7 .
When the driving member 7 rotates an angle, the variable resistance changes its resistance value so as to generate a voltage value by which the current position of the driving shaft 6 is detected. The current position is compared with a pre-set position, if the two positions are different, the motor 2 drives the reduction device 3 to rotate the driving shaft 6 to the pre-set position.
As shown in FIG. 5 , which discloses the flow chart of the main circuit of the circuit board 5 and includes the following steps.
step 10 shows that after the driving device of head light is activated, the main circuit begins to operate. The step 11 shows that the microprocessor control unit of the main circuit is initialized and the counting condition is zeroed. The microprocessor control unit also detects parts in the main circuit and making judgement of error.
Step 12 judges the current position of the driving shaft 6 , if the current position of the driving shaft 6 cannot be detected, step 18 is activated to activate the motor 2 and the counting condition is added by one and stored as record. In the step 18 , judging whether the number of the counting condition is over three which is pre-set, if the number of the counting condition is less than three, the step 12 is repeated, if the number is over three, an error judgement as disclosed in step 21 is made and process step 17 to stop the main circuit. If the current position is detected, then the step 13 is processed.
During the step 13 , the microprocessor control unit obtains the pre-set position and records the position. The pre-set position and the current position obtained in step 12 are compared with each other, if the result of comparison is different, the motor 2 drives the driving shaft 6 to the pre-set position. If the two positions are the same, then the step 14 is processed.
Step 14 is to judge whether the driving shaft 6 is returned to the pre-set position, if the driving shaft 6 is not returned to the pre-set position, the counting condition is added by one and stored as record as disclosed in step 20 . Step 18 is activated to judge whether the number of the counting condition is over pre-set times which is three, if the number of the counting condition is less than the pre-set times, repeat steps 12 to 14 . If the number is over the pre-set times and the driving shaft 6 is not returned to its pre-set position, an error judgement is made as disclosed in step 21 and the main circuit is stopped as disclosed in step 17 . On the contrary, if the driving shaft 16 is returned to its pre-set position by the judgement in step 14 , then step 15 is processed.
Step 15 is to judge whether the number of the revolution, the operation time or the electric current passing through of the motor is in a range of restriction. If the factor that mentioned above of the motor exceeds the range of restriction, the counting condition is added by one and stored as record as disclosed in step 20 . The step 18 judges whether the number of counting condition is over three, if the number is less than three, then repeat steps 12 to 15 , if the number is over three, an error judgement is made by step 21 and the step 17 cuts off the main circuit. On the contrary, if the step 15 judges that the number of the counting condition is not exceeded, the process step 16 .
When processing the step 16 , the driving module of the driving device is set and the driving device is ready to active. The driving device is ready to accept commands from the microprocessor control unit and the step 17 cuts off the main circuit.
As shown in FIG. 6 , there are three ways to detect the current position of the driving shaft 6 , the first way is to use the detection circuit composed of the sensor 51 on the circuit board 5 as shown in FIG. 2 to detect the current position of the driving shaft 6 .
When processing the step 12 to obtain the current position of the driving shaft 6 , the step 121 is processed in the same to zero the counting condition and the step 1211 is also processed.
In step 1211 , the sensor 51 detects a change of magnetic field of a magnet 42 in a driving member 4 so as to obtain a conference number which is sent to the MCU and transferred into a position reference number. After the step 1211 is completed, the step 1212 is processed wherein the transferred position reference number is compared with pre-set position reference number to judge if a result of the comparison exceeds a pre-set range of the position reference number. If the result of comparison is within the range of the pre-set position reference number, the current position of the driving shaft 6 is obtained by the step 1213 and the step 1214 eliminates the processes for obtaining the current position and the main circuit process in step 13 as shown in FIG. 5 starts. On the contrary, if the result of comparison is not located within the range of the pre-set position reference number, an error judgement is made by the step 1215 and the step 1214 eliminates the processes for obtaining the current position and the main circuit process in step 19 as shown in FIG. 5 starts.
As shown in FIG. 7 , the second way for obtaining the current position of the driving shaft 6 uses a detection circuit composed of a sensor 51 of the circuit board 5 as shown in FIG. 2 and a quadrature A/B circuit. The quadrature circuit generates a pulse “A” and a pulse “B” with a phase angle difference, if the pulse “A” leads a phase angle 90 degrees from the pulse “B”, the a first pre-set process is processed. If the pulse “B” leads a phase angle 90 degrees from the pulse “A”, a second pre-set process is processed.
When processing the step 12 to obtain the current position of the driving shaft 6 , the step 122 is processed in the same to zero the counting condition and the step 1221 is also processed.
The step 1221 judges whether the driving shaft 6 is returned to its pre-set position which is the original position, if the driving shaft 6 did not returned to the pre-set position in the record of the MCU, step 1223 is activated to activate the motor 2 to drive the driving shaft 6 back to its original position. This is recorded in the MCU and step 1222 begins to process. On the contrary, if the driving shaft 6 has been returned to the original position, then the step 1222 is processed.
In the step 1222 , the angular movement of the magnet 42 results in a change of magnetic field and the change generates a reference number which is sent to the quadrature circuit to generate the pulses “A” and “B” with a phase difference. The signal is sent to the MCU which transfers the signal into position reference number and the position reference number is recorded.
When the step 1222 is completed, the step 1224 is activated and the transferred position reference number is compared with pre-set position reference number to judge if a result of the comparison exceeds a pre-set range of the position reference number. The range is composed of different position references numbers collected by the angular movements of the magnet 42 . Each angular movement generates a change of magnetic field which is transferred to the MCU and transferred to different positioning reference numbers. If the result of comparison is within the range of the pre-set position reference number, the current position of the driving shaft is obtained by the step 1226 . The step 1227 eliminates the processes for obtaining the current position and the main circuit process in step 13 as shown in FIG. 5 starts. On the contrary, if the result of comparison is not located within the range of the pre-set position reference number, an error judgement is made by the step 1225 for the obtaining current position of the driving shaft. The step 1227 eliminates the processes for obtaining the current position and the main circuit process in step 19 as shown in FIG. 5 starts.
As shown in FIG. 8 , the third way to obtain the current position of the driving shaft 6 uses a detection circuit composed of a variable resistance 8 on the circuit board 5 as shown in FIG. 4 to detect the current position of the driving shaft 6 .
When processing the step 12 to obtain the current position of the driving shaft 6 , the step 123 is processed in the same to zero the counting condition and the step 1231 is also processed.
When processing the step 1231 , the MCU obtains the reference voltage which comes from the change of the resistance of the variable resistance 8 when the driving member 7 rotates.
After the reference voltage is obtained in step 1231 , step 1232 is processed and the reference voltage is compared with pre-set voltage to judge if a result of the comparison exceeds a pre-set range of the voltage, if the result of comparison is within the range of the pre-set voltage, the current position of the driving shaft 6 is obtained, and the step 1235 eliminates the process for obtaining the current position and the main circuit process as disclosed in step 13 as shown in FIG. 5 begins. If the result of comparison is not located within the range of the pre-set voltage, an error judgement is made for the current position of the driving shaft 6 by step 1234 and the step 1235 eliminates the process for obtaining the current position and the main circuit process as disclosed in step 13 as shown in FIG. 5 begins.
The method for returning the driving shaft 6 back to its pre-set position in step 13 as disclosed in FIG. 5 is described hereinafter.
As shown in FIG. 9 , after the main circuit process obtains the current position of the driving shaft 6 in step 12 , the step 130 is activated to activate the motor 2 to drive the driving shaft 6 back to its pre-set position.
Then the step 131 begins to obtain a pre-set position from the MCU and records the pre-set position, the counting condition is zeroed.
Then the step 132 records the current position of the driving shaft 6 and the current position can be obtained by the methods mentioned above.
Then the step 133 , the current position and the pre-set position are compared, if the two positions are not the same, the motor 2 is activated one more action or the motor reduces one action. In other words, the motor 2 rotates an angle clockwise or counter clockwise to drive the driving shaft 6 .
Then the step 134 , the MCU records the operation time of the motor 2 .
Then the step 135 compares the operation time of the motor 2 recorded in step 134 and the pre-set period of time of the operation of the motor 2 , if the actual operation time is longer than the pre-set period of time of the motor 2 , the step 138 judges that the motor 2 operates too long and the step 139 stops the operation of the motor 2 . The main circuit process in step 14 as shown in FIG. 5 starts. On the contrary, if the actual operation time is shorter than the pre-set period of time of the motor 2 , the step 136 judges that the driving shaft 6 is in its pre-set position. If the driving shaft 6 has not yet arrived its pre-set position, then steps 132 to 136 are repeated to drive the motor 2 . If the driving shaft 6 has arrived its pre-set position, then step 137 judges that the action is completed and the step 139 stops the motor 2 and the main circuit process in step 14 as shown in FIG. 5 starts.
The present invention provides thee ways to detect the current position of the driving shaft so that the users have different options to detect the driving shaft. After the driving device is activated, the users know that the status of the driving device, if an error is detected, the users can correct it before driving on the roads.
While we have shown and described the embodiment in accordance with the present invention, it should be clear to those skilled in the art that further embodiments may be made without departing from the scope of the present invention.
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A method for detecting errors in driving device of head light of vehicles utilizes a microprocessor control unit of a main circuit to detect the position of the driving shaft by checking the change of magnetic field or resistance of the driving member and the change of magnetic field or resistance is compared with a pre-set value to decide the position of the driving shaft. The motor is then commanded to drive the driving shaft to the pre-set position. The method detects the position of the head light before the drivers drive the vehicles on the road and if the head light is not in a desired position, the user can adjust the head light position to prevent potential risk on the road.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of U.S. provisional patent application No. 61/382,953, filed on Sep. 15, 2010.
BACKGROUND OF THE INVENTION
[0002] 1. Technical Field
[0003] Embodiments of the present invention relate generally to cryosurgical instruments such as cryoprobes and, more particularly, to cryosurgical instruments suitable for the ablation of a large volume of tissue.
[0004] 2. Description of Related Art
[0005] Cryosurgical ablation of a large volume of tissue typically involves placement of several (i.e., multiple) cryosurgical instruments within a defined volume to cause continuous ablation of the tissue in that volume.
[0006] Two principles are used to assist the physician to obtain the desired relationship between the cryosurgical instruments: some type of guide, such as an external template, or guiding sleeves; and clustering the cryosurgical instruments for insertion to the defined volume, typically simultaneously. The cryosurgical instrument penetrates the tissue along its main axes. The templates or the guiding sleeves can bend the flexible cryosurgical instrument and direct it in relationship to the other inserted cryosurgical instruments. However, the instrument may only be bent at a narrow angle, in order to maintain the integrity of the instrument.
[0007] The proper positioning of the cryosurgical instruments in relation to each other depends on the flexibility of the cryosurgical instruments, the diameter of the guide (and hence the degree of “play” or potential inaccuracy in guiding the instruments), and the skill of the physician. An instrument with greater flexibility may be more easily bent within the template or the sleeve, but once it is outside this guide, the instrument may bend further and so may not maintain the desired position. The diameter of the guiding element is always larger than the diameter of the cryosurgical instrument and therefore, further introduces error. Finally it is the judgment of the physician through the information received by the imaging tool, such as ultrasound imaging, CT or MRI, to determine whether the position of the cryosurgical instruments is adequate in three-dimensional space. Since the cryoablation volume induced by a single individual instrument is small in size, the relationship between the cryosurgical instruments is crucial to the success of the treatment. As a result, a physician may frequently insert more cryosurgical instruments than necessary to treat the required volume.
[0008] An additional challenge in the placement of several cryosurgical instruments in the selected tissue is caused by the deformability of human tissue, and the need for fixation of the organ within the body. To solve this problem two approaches are used: (1) cooling the first instrument to a temperature that effectively sticks the instrument to the tissue (creating contact surface of −20° C. or lower); or (2) holding the organ in place, using a mechanical anchor such as cork-screw element, while inserting several cryosurgical instruments into it.
[0009] The use of corkscrew (i.e., helical) type elements as mechanical anchors for various cryosurgical purposes is known (see, e.g., U.S. Pat. and Patent Publication Nos. 6,343,605, 6,004,269, 7,567,838, 2006/0253080, 2009/0292279 and 2010/0015196) or as a grasper (see. e.g., U.S. Patent Publication No. 2008/0294179).
[0010] The use corkscrew type elements to attach other components to each other is also known (see, e.g. , U.S. Pat. Nos. 4,917,106 and 5,195,540 and U.S. Patent Publication No. 2006/0259050). Similarly, a thermocouple has been attached to the cork screw element as a sensor during surgery (see, e.g., U.S. Pat. Nos. 5,800,432, 5,688,266, 5,688,267, 6,053,912, and 5,735,846.
[0011] A corkscrew type element has been also used to transmit electrical signals (see, e.g., U.S. Pat. No. 5,6269,272 and U.S. Patent Publication No. 2005/0101984), and as a RF electrode (see, e.g., U.S. Patent Publication 2004/0147917).
[0012] A corkscrew element has also been used as a biopsy tissue sampler (see, e.g., U.S. Pat. Nos. 4,682,606 and 6,142,957 and U.S. Patent Publication No. 2004/0147917) and as a lesion marker (U.S. Pat. No. 5,195,540) or as a vertebral support (U.S. Patent Publication No. 2008/0140203).
BRIEF SUMMARY
[0013] The background art does not provide, however, a helical element, introduced by rotation, suitable for cryosurgical applications, in which the element transmits cryogens and ablates a large volume of tissue without the placement of several (i.e., multiple) cryosurgical instruments within a defined volume to cause continuous ablation of the tissue in that volume.
[0014] One aspect of the present invention provides a cryosurgical instrument that is selectively positioned in a patient by rotation, including: a manipulation section that permits a user to rotate the instrument; a cryogen supply portion; and a positioning section having a sharp tip at an end thereof and a helical configuration, the positioning section configured to receive cryogen from the cryogen supply portion and to permit the received cryogen to cool the positioning section.
[0015] A further aspect of the present invention provides a cryosurgical instrument having a substantially smooth, temperature conducting outer surface with an inner side, including: a sharp tip at an end to facilitate penetration into tissue; one or more cryogen supply lines that supply cryogen to the instrument; a manipulation section for positioning the instrument, at least a portion of the manipulation section extending along and defining a longitudinal axis of the instrument, the manipulating section having insulation along at least a portion of a length thereof, and a return fluid sleeve to permit exhaust of expanded fluid from the instrument; a cooling section connected to the manipulation section, extending from the manipulation section to the tip, and having a helical configuration spiraling around the longitudinal axis, and a heat exchanger in fluid communication with the one or more cryogen supply lines, surrounding the one or more cryogen supply lines in the cooling section, and delivering received cryogen to a port at a distal end thereof proximal to the tip, the heat exchanger including a plurality of channels that are circumferentially disposed along the inner side of the outer surface and that interconnect the one or more supply lines to the a return gas sleeve, the heat exchanger permitting cryogen from the one or more supply lines to cool the cooling section; and an expanded fluid return pathway surrounding the one or more cryogen supply lines and bounded by the one or more cryogen supply lines and the inner side of the outer surface of the instrument so that gas in the pathway is in thermal communication with the inner side.
[0016] Another aspect of the present invention provides a cryosurgical instrument having a substantially smooth, temperature conducting outer surface with an inner side, including: a sharp tip at an end to facilitate penetration into tissue; a manipulation section for positioning the instrument, at least a portion of the manipulation section extending along and defining a longitudinal axis of the instrument, the manipulating section having insulation along at least a portion of its length; a cooling section connected to the manipulation section, extending from the manipulation section to the tip, and having a helical configuration spiraling around the longitudinal axis; one or more cryogen supply lines that supply cryogen to the instrument, each supply line delivering cryogen to one or more ports along a portion of a length thereof in the cooling section, at least one of the supply lines having a port at a distal end thereof proximal to the tip; and a return fluid sleeve to permit exhaust of expanded gas from the instrument, the sleeve surrounding the one or more cryogen supply lines and bounded by the one or more cryogen supply lines and the inner side of the outer surface of the instrument so that fluid in the sleeve is in thermal communication with the inner side, the sleeve permitting cryogen from the one or more supply lines to cool the cooling section.
[0017] Still another aspect of the present invention provides a cryosurgical instrument having a substantially smooth, temperature conducting outer surface with an inner side, including: a sharp tip at an end to facilitate penetration into tissue; a cryogen supply line that delivers cryogen to a port at an end proximal to the tip; a manipulation section for positioning the instrument, at least a portion of the manipulation section extending along and defining a longitudinal axis of the instrument, the manipulating section having insulation along at least a portion of a length thereof, and a return fluid sleeve to permit exhaust of expanded gas from the instrument; a cooling section connected to the manipulation section, extending from the manipulation section to the tip, and having a helical configuration spiraling around the longitudinal axis, and a barrier that is disposed only in the cooling section and spirals about the cryogen supply line, the barrier yielding a spiraling channel that is circumferentially disposed along the inner side of the outer surface, that is bounded by the cryogen supply line and the inner side of the outer surface of the instrument, and that interconnects the supply line to the a return gas sleeve, the barrier permitting cryogen exiting the port to cool the cooling section.
[0018] Yet another aspect of the present invention provides a cryosurgical instrument having a substantially smooth, temperature conducting outer surface with an inner side, including: a sharp tip at an end to facilitate penetration into tissue; a cryogen supply line that delivers cryogen to a port at an end proximal to the tip; a manipulation section for positioning the instrument, at least a portion of the manipulation section extending along and defining a longitudinal axis of the instrument, the manipulating section having insulation along at least a portion of a length thereof, and a return fluid sleeve to permit exhaust of expanded gas from the instrument; a cooling section connected to the manipulation section, extending from the manipulation section to the tip, and having a helical configuration spiraling around the longitudinal axis, and a core that is disposed only in the cooling section and that extends from the manipulating section to substantially near the tip. The cryogen supply line spirals around the core. The spiraling of the cryogen supply line yields a spiraling channel that is circumferentially disposed along the inner side of the outer surface, that is bounded by the cryogen supply line and the inner side of the outer surface of the instrument, and that interconnects the supply line to the a return fluid sleeve, the spiraling channel permitting cryogen exiting the port to cool the cooling section.
[0019] Optionally, the cryosurgical instrument features a single tip and in operation, is used singly to ablate the large volume of tissue, without requiring the insertion of multiple cryosurgical instruments.
[0020] This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is neither intended to identify key features or essential features of the claimed subject matter, nor should it be used to limit the scope of the claimed subject matter. Furthermore, the claimed subject matter is not limited to implementations that solve any disadvantage noted in any part of this application.
[0021] These, additional, and/or other aspects and/or advantages of the present invention are: set forth in the detailed description which follows; possibly inferable from the detailed description; and/or learnable by practice of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] The present invention will be more readily understood from the detailed description of embodiments thereof made in conjunction with the accompanying drawings of which:
[0023] FIG. 1 a is a partial cut-away view of a cryosurgical instrument that is consistent with an embodiment of the present invention;
[0024] FIG. 1 b is a cross-sectional view of the cryosurgical instrument of FIG. 1 a taken along line A-A of FIG. 1 a;
[0025] FIG. 2 a is a partial cut-away view of a cryosurgical instrument that is consistent with an embodiment of the present invention;
[0026] FIG. 2 b is a cross-sectional view of the cryosurgical instrument of FIG. 1 a taken along line A-A of FIG. 1 a;
[0027] FIG. 3 is a side view of a cryosurgical instrument that is consistent with an embodiment of the present invention;
[0028] FIG. 4 is a side view of a cryosurgical instrument that is consistent with an embodiment of the present invention;
[0029] FIG. 5 a is a partial cut-away, side view of a cryosurgical instrument that is consistent with an embodiment of the present invention;
[0030] FIG. 5 b is a perspective view of a heat exchanger of the cryosurgical instrument of FIG. 5 a;
[0031] FIG. 5 c is a cross-sectional view of the cryosurgical instrument of FIG. 5 a taken along line A-A of FIG. 5 a;
[0032] FIG. 6 a is a partial cut-away, side view of a cryosurgical instrument that is consistent with an embodiment of the present invention;
[0033] FIG. 6 b is a cross-sectional view of the cryosurgical instrument of FIG. 6 a taken along line A-A of FIG. 6 a;
[0034] FIG. 7 is a partial cut-away, side view of a cryosurgical instrument that is consistent with an embodiment of the present invention;
[0035] FIG. 8 is a partial cut-away, side view of a cryosurgical instrument that is consistent with an embodiment of the present invention;
[0036] FIG. 9 is a partial cut-away, side view of a cryosurgical instrument that is consistent with an embodiment of the present invention;
[0037] FIGS. 10 a and 10 b respectively illustrate a system that is consistent with an embodiment of the present invention in a retracted and a protracted state; and
[0038] FIG. 11 is a side view of a cryosurgical instrument that is consistent with an embodiment of the present invention.
DETAILED DESCRIPTION
[0039] Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to the like elements throughout. The embodiments are described below to explain the present invention by referring to the figures.
[0040] Although the following text sets forth a detailed description of at least one embodiment or implementation, it is to be understood that the legal scope of protection of this application is defined by the words of the claims set forth at the end of this disclosure. The detailed description is to be construed as exemplary only and does not describe every possible embodiment since describing every possible embodiment would be impractical, if not impossible. Numerous alternative embodiments and/or implementations are both contemplated and possible, using either current technology or technology developed after the filing date of this patent, which would still fall within the scope of the claims.
[0041] It is to be understood that, unless a term is expressly defined in this application using the sentence “As used herein, the term’ ‘is hereby defined to mean . . . ” or a similar sentence, there is no intent to limit the meaning of that term, either expressly or by implication, beyond its plain or ordinary meaning, and such term should not be interpreted to be limited in scope based on any statement made in any section of this patent (other than the language of the claims). To the extent that any term recited in the claims at the end of this patent is referred to in this patent in a manner consistent with a single meaning, that is done for sake of clarity only so as to not confuse the reader, and it is not intended that such claim term is limited, by implication or otherwise, to that single meaning. Finally, unless a claim element is defined by reciting the word “means” and a function without the recital of any structure, it is not intended that the scope of any claim element be interpreted based on the application of 35 U.S.C. §112, sixth paragraph.
[0042] As used herein, “large volume of tissue” means a volume that is greater than that which may be ablated with a standard straight cryosurgical instrument, as is currently known in the art. As used herein, “standard cryosurgical instrument” means a (i.e., conventional) cryoprobe with a single cooling zone, inserted either along its main axis or approximately in that direction. One example of such a conventional cryprobe is a cryoneedle.
[0043] Turning now to the drawings, FIGS. 1 a and 1 b illustrate a cryosurgical instrument 100 that is consistent with an embodiment of the present invention. FIG. 1 a shows a partial cut-away of cryosurgical instrument 100 , while FIG. 1 b shows a cross-section thereof taken along line A-A of FIG. 1 a.
[0044] The cryosurgical instrument 100 comprises a manipulation section 110 distal to a tip 103 of the cryosurgical device and a cooling section 105 extending from the manipulating section 110 to the tip 103 .
[0045] The manipulating section 110 extends along and partially defines a longitudinal axis (not shown) of the cryosurgical instrument 100 . The manipulating section 110 includes insulation 108 along at least a portion of its length and a return gas sleeve 107 in gaseous communication with channels 109 to permit the exhaust of expanded/returning cryogen, as explained in detail below.
[0046] The cryosurgical instrument 100 features a helical portion 104 , with surface 101 that, when inserted into a patient, is in contact with the tissue of the patient. The helical portion 104 includes one or more spirals 111 , as illustrated, and terminates in a tip 103 that is preferably sharp to ease penetration into the tissue. Although two spirals are illustrated, it is to be understood that other numbers of spirals are both possible and contemplated. In this regard, the inventors have determined that a plurality of spirals 111 can be optimal in many cryosurgical applications. Further, the spirals of the helical portion 104 may be constant as illustrated or may vary in pitch and/or diameter.
[0047] The helical portion 104 may be disposed entirely within a cooling section 105 of the cryosurgical instrument 100 , as shown. Alternatively, the helical portion 104 may be disposed partially beyond the cooling section 105 .
[0048] Cryogen (liquid, compressed gas or mixtures of gases) enters the cryosurgical instrument 100 through one or more feeding lines 102 and travels, via a heat exchanger 106 , through the cryosurgical device toward the tip 103 .
[0049] Heat exchanger 106 receives the cryogen from the one or more feeding tubes 102 and delivers the cryogen to the tip 103 via port 113 , which is located proximal to the tip 103 . In more detail, the cryogen flows through the heat exchanger 106 , thereby cooling the heat exchanger 106 . And, since the heat exchanger 106 is in thermal communication with the outer surface 101 , the outer surface is, in turn, cooled. In this process, the cryogen either expands or evaporates and cools, through the Joules-Thompson effect or simple evaporation. The cryogen is emitted near tip 103 through a port 113 . Thereafter, the returning cryogen (cooled by the expansion, or evaporation) flows through the channels 109 , which is in contact with the inner surface of the cryosurgical instrument 100 , cooling the surface 101 . The cryogen is then exhausted in a return sleeve 107 that preferably runs within and through the inner diameter of the insulation 108 .
[0050] The inventors have discovered that for many cryosurgical applications, it can be preferable to extend the cooling section 105 to encompass the tip 103 . Tip 103 may optionally comprise a reflective surface 112 , as shown.
[0051] Referring specifically to FIG. 1 b, the arrangement of the one or more feeding lines 102 , the heat exchanger 106 , the channels 109 and the cooling surface 101 are illustrated. While six channels are illustrated, it is to be understood that other numbers are both possible and contemplated.
[0052] The cooling surface 101 may optionally comprise one or more of metal, ceramic material, or plastic. The cooling section 105 is terminated at proximal end by insulation 108 .
[0053] The use of the cryosurgical instrument 100 is discussed. The tip 103 of the cryosurgical instrument 100 is brought into contact with the tissue of a patient. Then sufficient force is applied to cause the tip 103 to pierce the skin of the patient. Contemporaneously or immediately thereafter, the cryosurgical instrument 100 is rotated in a manner akin to the insertion of a corkscrew into a cork so that the helical portion is embedded in the tissue. This rotational insertion causes the helical portion 104 to draw the instrument 101 toward/into the tissue to be ablated. Next, when the freezing portion 105 is positioned as desired, cryogen is supplied to cool the cooling section.
[0054] As the aforementioned description implies, the helical configuration of the cooling section 105 serves as a positioning section.
[0055] When the helical portion 104 is firmly embedded in the tissue of a patient, the spiral arrangement secures the cryosurgical instrument in the tissue. Also, when in the body, the instrument 100 can be positioned with far less forward or rearward pressure than conventional cryoprobes since the selective rotation of the helical portion 104 urges the instrument into the instrument into the body or urges the instrument out of the body. Further, the instrument 100 can be positioned with a majority of the force applied to the instrument applied to rotate the instrument.
[0056] FIGS. 2 a and 2 B illustrate another example of a cryosurgical instrument consistent with an embodiment of the present invention. FIG. 2 a shows a partial cut-away of cryosurgical instrument 200 , while FIG. 2 b shows a cross-section thereof taken along line A-A of FIG. 2 .
[0057] In a cryosurgical instrument 200 , the cryogen cools surface 201 , by either expansion or evaporation, with the assistance of a plurality of discrete heat exchange elements 206 , featuring grooves 209 . A plurality of grooved heat exchange elements 206 is disposed in multiple locations along the cooling section 205 of the length of the cryosurgical device 200 . Specific locations for the heat exchange elements depend on the desired volume of ablation.
[0058] The cryosurgical instrument 200 features a helical portion 204 , with surface 201 that, when inserted into a patient, is in contact with the tissue of the patient. The helical portion 204 includes one or more spirals 211 , as illustrated, and terminates in a tip 203 that is preferably sharp to ease penetration into the tissue. Although two spirals are illustrated, it is to be understood that other numbers of spirals are both possible and contemplated. In this regard, the inventors have determined that a plurality of spirals 211 can be optimal in many cryosurgical applications. Further, the spirals of the helical portion 204 may be constant as illustrated or may vary.
[0059] The helical portion 204 is disposed entirely within a cooling section 205 of the cryosurgical instrument 200 , as shown. Alternatively, the helical portion 204 may be disposed partially beyond the cooling section 205 .
[0060] Cryogen (liquid, compressed gas or mixtures of gases) enters the cryosurgical instrument 200 through one or more feeding lines 202 and travels to port 213 , which is proximal to the tip 203 .
[0061] The heat exchange elements 206 operate in a manner similar to the heat exchanger 106 of FIG. 1 a, where the grooves 209 allow the flow of the cryogen into the return gas sleeve 207 , thereby cooling the inner surface of cryosurgical instrument 200 at a plurality of locations as shown. Such cooling causes freezing of tissue that is in contact with the cooling surface 201 . The absorption of the heat from the tissue occurs throughout the cooling section 205 by either conduction through the cooled surfaces of the grooved heat exchange elements 206 or by flow of cryogen in contact with the inner surface of cryosurgical instrument 100 , up to the return fluid sleeve 207 , or both. Insulation 208 keeps the manipulation section 210 from being cooled by the cryogen.
[0062] The inventors have discovered that for many cryosurgical applications, it can be preferable to extend the cooling section 205 to encompass the tip 203 . Tip 203 may optionally comprise a reflective surface 212 , as shown.
[0063] Preferably the distribution of the grooved heat exchange elements is sufficient to yield a single, continuous ablations zone. However, the inventors also contemplate distributions that provide discrete ablations zones along segments of the length of the helical portion 204 .
[0064] FIG. 3 shows another example of another cryosurgical instrument consistent with an embodiment of the present invention.
[0065] The cryosurgical instrument 300 features a helical portion 304 that includes several spirals 311 such that the freezing portion spirals more than 360 degrees. Optionally any type of heat exchange element, such as the above-described grooves may be employed (not shown). The surface area in the cooling section 305 is therefore greater than the equivalent cooling surface of the systems of FIGS. 1 a - 2 b.
[0066] FIG. 4 shows another example of a cryosurgical instrument consistent with an embodiment of the present invention. In cryosurgical instrument 400 , the cryogen may optionally comprise any type of fluid and can be adapted for Joule-Thomson cooling. As is known in the art, Joule-Thomson cooling is based upon the Joule-Thomson effect, in which a compressed fluid is forced through a narrow opening, resulting in rapid expansion of the compressed fluid, and cooling of the fluid.
[0067] The cryosurgical instrument 400 features a helical portion 404 , with surface 401 that, when inserted into a patient, is in contact with the tissue of the patient. The helical portion 404 includes one or more spirals 411 , as illustrated, and terminates in a tip 403 that is preferably sharp to ease penetration into the tissue. Although two spirals are illustrated, it is to be understood that other numbers of spirals are both possible and contemplated. In this regard, the inventors have determined that a plurality of spirals 411 can be optimal in many cryosurgical applications. Further, the spirals of the helical portion 404 may be constant as illustrated or may vary.
[0068] The helical portion 404 is disposed entirely within a cooling section 405 of the cryosurgical instrument 400 .
[0069] Cryogen (liquid, compressed gas or mixtures of gases) enters the cryosurgical instrument 400 through cryogen feed line 402 and travels toward the tip 103 .
[0070] To support the Joule-Thomson effect, cryosurgical instrument 400 preferably features one or more adiabatic nozzles 413 to introduce the fluid cryogen into the inner area of cryosurgical instrument 400 . Upon expansion or evaporation of the cryogen, depending on the type of fluid, the surface 401 is cooled generating the cooling section 405 . Optionally, nozzle(s) 413 may be provided as ports or other openings (not shown).
[0071] Alternatively, if one adiabatic expansion nozzle 413 is used, the adiabatic expansion nozzle 413 is preferably located at or near tip 403 . If a plurality of nozzles 413 is used, such adiabatic expansion nozzles 406 are preferably installed at multiple locations along the inlet feeding tube 402 , more preferably distributed more or less equally. Such one or more adiabatic expansion nozzles 413 let part, or all, of the pressurized cryogen flowing in the cryogen feed line 402 , to exit and expand. The cryogen feed line 402 delivers the cryogen, or portion of it if a plurality of nozzles 413 is present, to the tip 403 .
[0072] The inventors have discovered that for many cryosurgical applications, it can be preferable to extend the cooling section 405 to encompass the tip 403 . Tip 403 may optionally comprise a reflective surface 412 , as shown. In addition, heat regenerating coils, not shown, may be added within the supply tube 402 and/or at each port 406 , to cool the compressed fluid before it is ejected from each port.
[0073] FIGS. 5 a - 5 c show an example of another cryosurgical instrument consistent with an embodiment of the present invention. FIG. 5 a shows a partial cut-away view of the cryosurgical instrument 500 . FIG. 5 b is a perspective view of the helical grooves 509 in relation to cryogen supply line 502 . FIG. 5 c is a cross-sectional view taken along line A-A of FIG. 5 a.
[0074] The cryosurgical instrument 500 features a helical portion 504 , with surface 501 that, when inserted into a patient, is in contact with the tissue of the patient. The helical portion 504 includes one or more spirals 511 , as illustrated, and terminates in a tip 503 that is preferably sharp to ease penetration into the tissue. Although two spirals are illustrated, it is to be understood that other numbers of spirals are both possible and contemplated. In this regard, the inventors have determined that a plurality of spirals 511 can be optimal in many cryosurgical applications. Further, the spirals of the helical portion 504 may be constant as illustrated or may vary.
[0075] The helical portion 504 is disposed entirely within a cooling section 505 of the cryosurgical instrument 500 .
[0076] Cryogen (liquid, compressed gas or mixtures of gases) enters the cryosurgical instrument 500 through cryogen feed line 502 and travels to the tip 503 .
[0077] In cryosurgical instrument 500 , a plurality of discrete heat exchange elements 506 are disposed at various locations along a cryogen supply line 502 in a cooling zone 505 . Preferably each of the heat exchange elements 506 comprises a plurality of helical channels 509 . The cryogen supplied by input feeding line 502 then flows back to the return sleeve 507 , cooling the surface 501 by either direct contact of the cryogen flowing along the spaces created between the helical channels 509 and the outer surface of the instrument, or by conduction of heat via the contact surfaces of heat exchange elements 506 and the inner surface of cryosurgical instrument 500 , thereby cooling surface 501 .
[0078] As shown in FIG. 5 b , the channels 509 spiral about the cryogen supply line.
[0079] Although only a single cryogen supply line 502 is shown, it is to be understood that multiple cryogen supply lines are both possible and contemplated. Also, when multiple cryogen supply lines 502 are present, each line may have multiple heat exchange elements 506 .
[0080] The inventors have discovered that for many cryosurgical applications, it can be preferable to extend the cooling section 505 to encompass the tip 503 . Tip 503 may optionally comprise a reflective surface 512 , as shown.
[0081] FIGS. 6 a and 6 b show another example of cryosurgical instrument consistent with an embodiment of the present invention. FIG. 6 a shows a partial cut-away view while FIG. 6 b shows a cross-sectional view along line A-A of FIG. 6 a.
[0082] The cryosurgical instrument 600 features a helical portion 604 , with surface 601 that, when inserted into a patient, is in contact with the tissue of the patient. The helical portion 604 includes one or more spirals 611 , as illustrated, and terminates in a tip 603 that is preferably sharp to ease penetration into the tissue. Although two spirals are illustrated, it is to be understood that other numbers of spirals are both possible and contemplated. In this regard, the inventors have determined that a plurality of spirals 611 can be optimal in many cryosurgical applications. Further, the spirals of the helical portion 604 may be constant as illustrated or may vary.
[0083] The helical portion 604 is disposed entirely within a cooling section 605 of the cryosurgical instrument 600 .
[0084] The cryosurgical instrument 600 includes a cryogen feeding input line 602 to feed cryogen to a single heat exchange element 606 having helical channels 609 that extend from a tip 603 to a return gas sleeve 607 . In operation, cryogen enters the cryosurgical instrument 600 via input line 602 , cools the heat exchanger 606 , is discharged through a port 613 proximal to the tip 603 , flows back through the helical channels 609 to the return fluid sleeve 607 thereby cooling the surface 601 by either: (1) direct contact of the cryogen flowing along the helical groove 609 ; or (2) conduction of heat via the contact surface of heat exchange element 606 and the inner surface of cryosurgical instrument 600 thereby cooling the surface 601 , throughout the cooling zone 605 .
[0085] Referring to FIG. 6 b , the relationship between the spiral grooves 609 and the feed line 602 are illustrated.
[0086] The inventors have discovered that for many cryosurgical applications, it can be preferable to extend the cooling section 605 to encompass the tip 603 . Tip 603 may optionally comprise a reflective surface 612 , as shown.
[0087] FIG. 7 shows another example of a cryosurgical instrument consistent with an embodiment of the present invention. The cryosurgical instrument 700 features insulation 708 disposed on the outer surface of the cryosurgical device in the manipulation zone 710 . In this example, a cryogen feeding input line 702 feeds cryogen to a single heat exchange element 706 , which delivers the cryogen to port 713 located proximal to the tip 703 .
[0088] In more detail, the cryosurgical instrument 700 features a helical portion 704 , with surface 701 that, when inserted into a patient, is in contact with the tissue of the patient. The helical portion 704 includes one or more spirals 711 , as illustrated, and terminates in a tip 103 that is preferably sharp to ease penetration into the tissue. Although two spirals are illustrated, it is to be understood that other numbers of spirals are both possible and contemplated. In this regard, the inventors have determined that a plurality of spirals 711 can be optimal in many cryosurgical applications. Further, the spirals of the helical portion 704 may be constant as illustrated or may vary.
[0089] The helical portion 704 is disposed entirely within a cooling section 705 of the cryosurgical instrument 700 .
[0090] The inventors have discovered that for many cryosurgical applications, it can be preferable to extend the cooling section 705 to encompass the tip 703 . Tip 703 may optionally comprise a reflective surface 712 , as shown.
[0091] The inventors have discovered that for many cryosurgical applications, it can be preferable to extend the cooling section 705 to encompass the tip 703 . Tip 703 may optionally comprise a reflective surface 712 , as shown.
[0092] FIG. 8 shows an example of another cryosurgical instrument 800 consistent with an embodiment of the present invention.
[0093] The cryosurgical instrument 800 features a helical portion 804 , with surface 801 that, when inserted into a patient, is in contact with the tissue of the patient. The helical portion 804 includes one or more spirals 811 , as illustrated, and terminates in a tip 803 that is preferably sharp to ease penetration into the tissue. Although two spirals are illustrated, it is to be understood that other numbers of spirals are both possible and contemplated. In this regard, the inventors have determined that a plurality of spirals 811 can be optimal in many cryosurgical applications. Further, the spirals of the helical portion 804 may be constant as illustrated or may vary.
[0094] The helical portion 804 is disposed entirely within a cooling section 805 of the cryosurgical instrument 800 .
[0095] In cryosurgical instrument 800 , a cryogen feeding input line 802 delivers cryogen to a tip 803 . The cryosurgical instrument 800 also includes a barrier 816 that urges the flow of returning cryogen toward outer surface 801 of the cryosurgical instrument 800 so as to cool surface 801 . Barrier 816 effectively forces the return fluid to flow in an open space 819 between the barrier 816 from tip 803 to the return gas sleeve 807 , creating the cooling zone 805 . The cooling zone 805 ends at insulation 808 that is located in manipulation zone 810 .
[0096] The barrier 816 is illustrated as a coiled tube. However, it is to be understood that other configurations are both possible and contemplated. Indeed, the barrier 816 need not have the round cross-section as shown. Rather, any cross-section that urges the return flow towards the outer surface may be used. Also, the barrier may spiral with constant pitch as illustrated. Alternatively, the barrier 816 may spiral at a varied pitch.
[0097] The inventors have discovered that for many cryosurgical applications, it can be preferable to extend the cooling section 805 to encompass the tip 803 . Tip 803 may optionally comprise a reflective surface 812 , as shown.
[0098] FIG. 9 shows an example of a cryosurgical instrument 900 consistent with an embodiment of the present invention.
[0099] The cryosurgical instrument 900 features a helical portion 904 , with surface 901 that, when inserted into a patient, is in contact with the tissue of the patient. The helical portion 904 includes one or more spirals 911 , as illustrated, and terminates in a tip 903 that is preferably sharp to ease penetration into the tissue. Although two spirals are illustrated, it is to be understood that other numbers of spirals are both possible and contemplated. In this regard, the inventors have determined that a plurality of spirals 911 can be optimal in many cryosurgical applications. Further, the spirals of the helical portion 904 may be constant as illustrated or may vary.
[0100] The helical portion 904 is disposed entirely within a cooling section 905 of the cryosurgical instrument 800 .
[0101] In cryosurgical instrument 900 , a cryogen feeding input line 902 is coiled around a solid core 915 , from the return fluid sleeve 907 to the tip 903 , ending with port 913 at which the cryogen is left to flow within the cooling surface 901 . In operation, cryogen flowing in the coiled line 902 cools the surface of the coiled tube 902 . This surface, in turn, cools the inner surface of the cryosurgical instrument 900 , which, in turn, is in thermal communication with and cools the cooling surface 901 . After the cryogen exits the supply line 902 at a port 913 , it flows back through the gap 919 created by the inlet tube 902 as a barrier next to the inner surface of cryosurgical instrument 900 .
[0102] The cryogen supply line 902 may spiral at a constant rate as illustrated. Alternatively, the cryogen supply line 902 may spiral at a varied rate.
[0103] The inventors have discovered that for many cryosurgical applications, it can be preferable to extend the cooling section 905 to encompass the tip 903 . The cooling zone 905 ends at insulation 908 that is located in a manipulation section (not shown). Tip 903 may optionally comprise a reflective surface 912 , as shown.
[0104] FIGS. 10 a and 10 b show an example of a system that includes a cryosurgical instrument consistent with an embodiment of the present invention. FIG. 10 a illustrates a system 1000 with a flexible cryosurgical instrument 1001 . The instrument 1001 includes a helical section 1004 and a sharp tip 1003 . The instrument 1001 is selectively retractable into (i.e., drawn into) a sleeve 1020 of, for example a trocar, and selectively protractable from (i.e., extendable from) the sleeve 1020 . To facilitate this functionality, the instrument 1001 is flexible and compressible. Optionally, the cryosurgical instrument may be made of material with memory.
[0105] Following the insertion of the cryosurgical instrument 1001 through the sleeve 1020 , the mechanical flexibility of the instrument 1001 , an applied pressure, and/or a temperature increase, causes the instrument to expand from the retracted condition shown in FIG. 10 a to the protracted condition as shown in FIG. 10 b . Cryosurgical instrument 1001 may be any instrument consistent with any embodiment of the present invention.
[0106] FIG. 11 shows an example of another cryosurgical instrument consistent with an embodiment of the present invention. FIG. 11 a shows a side view of cryosurgical instrument 1100 , while FIG. 1 b shows a cross-section thereof taken along line A-A of FIG. 11 a.
[0107] Cryosurgical instrument 1100 features a plurality of individual cryosurgical instruments 1101 arranged in a cluster, each with the same pitch and outside diameter. The plurality may include three instruments, as illustrated, although other numbers are both contemplated and possible. Also, all of the instruments may be the same instrument as illustrated, or a combination of different cryosurgical instruments.
[0108] Each cryosurgical instrument 1101 may be any instrument consistent with any embodiment of the present invention.
[0109] The cooling sections 1105 of each instrument 1101 may spiral about the longitudinal axis at a diameter and pitch that differs from those of the other cooling sections of the other instruments. Alternatively, the cooling sections 1105 of each instrument 1101 may spiral about the longitudinal axis at a diameter and pitch that is the same as those of the other cooling sections of the other instruments.
[0110] The use of each of cryosurgical instruments 200 , 300 , 400 , 500 , 600 , 700 , 800 , 900 , 1000 , and 1101 is substantially similar to that of cryosurgical instrument 100 .
[0111] As the foregoing shows, a specially shaped cryosurgical instrument has been devised that facilitates: placing several cryoprobes, or cryo-coolers, closely in relation to one another; positioning them in flexible unfixed organ; and eliminating the need for a guide. The novel cryosurgical instrument penetrates the tissue by rotation. The treatment of the large volume of tissue is achieved by either several cooling elements, prepositioned, or by cooling the whole surface of defined ablation zone. The prepositioned ablating elements eliminate the needed skill of the physician to place several small cryosurgical instruments in relation to one another to create continuous volume of ablation. Consequently, the need to penetrate the tissue in several places is avoided. In addition, because of its shape, the novel instrument is anchored in the tissue to retain it in its position during thawing part of the process without an additional holding force.
[0112] An aspect of the present invention provides a cryosurgical instrument including a helical element that receives a cryogenic fluid and a tip that is cooled by the cryogenic fluid. The portion of the instrument that is cooled by the cryogenic fluid may optionally include an extended distal section of the instrument that, together with the tip, is a cooling zone. Upon insertion to a tissue the cooling zone is cooled and causes an ice ball to form, thereby causing cryoablation of the tissue volume defined by the ablation zone of the instrument.
[0113] As the foregoing also shows, cryosurgical instruments according to at least some embodiments of the present invention overcome the above drawbacks of the background art, including but not limited to, the requirement to insert several cryosurgical instrument in a defined spatial volume and in relation to each other, to position such cryosurgical instruments in a flexible unfixed organ, and the need for a template or guiding element.
[0114] Cryosurgical instruments according to at least some embodiments of the present invention, featuring at least one helical element, penetrate the tissue by rotation. By turning the instrument, the tip and the body of the instrument penetrate deep into the tissue. The treatment of the large volume of tissue is achieved by either several cooling elements, prepositioned within or attached to the cryosurgical instrument, or by cooling the whole surface of defined ablation zone. The prepositioned ablating elements eliminate the needed skill of the physician to place several small cryosurgical instruments in relation to one another to create a continuous volume of ablation. Another advantage is the creation of a single hole, rather than multiple holes as for the background art instruments. This instrument is also, inherently from its shape, anchored in the tissue and optionally no additional holding force is required to retain it in its position during thawing part of the process.
[0115] As previously described, at least a portion of the cryosurgical instrument is in the shape of a spiral or corkscrew element, with a tip that is preferably a sharp penetrating tip. As the instrument enters the tissue to be ablated, rotation of the instrument causes the penetration thereof into the tissue. The depth of the penetration is determined by the size of the corkscrew element; however the freezing ablation zone volume is extended further out and forwards depending on the pitch and outside diameter of the spiral and the cooling capacity. The freezing element may either utilize the Joule-Thomson effect caused by expanded high-pressure gas, or evaporating liquefied gas. Heating the element to either thaw the frozen tissue or to release the instrument from the tissue, can be done by either supplying high pressure gas that heats upon expansion (Joule-Thomson method), supplying a heated gaseous form of the liquefied freezing cryogen, or supplying electrical power to specially placed heating elements.
[0116] The use of various ones of the above-described examples is discussed. Generally, the shape of the cryosurgical instrument is a spiral type, with a sharp penetrating tip. As the instrument brought into contact with the desired ablated volume, the instrument is rotated, which causes the penetration of the tissue since the turning causes a forward motion like “cork screw”. The size of the penetration is the size of external tube; however the freezing ablation zone is extended further outward and forward depending on the pitch and outside diameter of the spiral and the cooling capacity. The freezing element may either utilize the Joule-Thomson effect caused by expanded high-pressure gas, or evaporating liquefied gas. Heating the element to either thaw the frozen tissue or to release the instrument from the tissue, can be done by either supplying high pressure gas which heats upon expansion (Joule-Thomson effect), supplying a heated gaseous form of the liquefied freezing cryogen, or supplying electrical power to specially placed heating elements.
[0117] Examples of various features/aspects/components/operations have been provided to facilitate understanding of the disclosed embodiments of the present invention. In addition, various preferences have been discussed to facilitate understanding of the disclosed embodiments of the present invention. It is to be understood that all examples and preferences disclosed herein are intended to be non-limiting.
[0118] Although selected embodiments of the present invention have been shown and described individually, it is to be understood that at least aspects of the described embodiments may be combined.
[0119] Although selected embodiments of the present invention have been shown and described, it is to be understood the present invention is not limited to the described embodiments. Instead, it is to be appreciated that changes may be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and the equivalents thereof.
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A cryosurgical instrument that is selectively positioned in a patient tissue by rotation. The instrument includes: a manipulation section that permits a user to rotate the instrument; a cryogen supply portion; and a positioning section having a sharp tip at an end and a helical configuration, the positioning section configured to receive cryogen and to permit the received cryogen to cool the positioning section. The positioning section urges the cryosurgical instrument deeper into the patient when the instrument is rotated in a first direction, via the manipulation section, and urges the cryosurgical instrument outward when the instrument is rotated in a second direction that is opposite the first, via the manipulation section.
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BACKGROUND OF THE INVENTION
Tall fescue has good forage quality for grazing animals in that it has adequate crude protein and satisfactory digestabilty. However, animals often perform poorly on it and suffer from various disorders such as "fescue foot", characterized in rough coats, weight loss, fever, tenderness or loss of hooves and tails and sometimes death; "bovine fat necrosis", characterized in hard masses of fat along the intestinal tract resulting in digestive upsets and difficult births; and "fescue toxicity", also called "summer slump" because of its common incidence in hot weather, characterized in poor weight gain, reduced conception weights and intolerance to heat.
Higher levels of incidence to fescue toxicosis have been observed in fields infected with certain fungi, in particular endophytic fungi (See Schmidt et al. Journal of Animal Science 55 1260-1263 (1982) Hoveland et al. Agronomy Journal 72 pg 375-377 (1980) and Hoveland et al. Circular 270 from Alabama Agricultural Experiment Station, Auburn University, Alabama (1984)). Certain researchers have compared pastures of tall fescue with and without contamination by the fungus Acremoniun coenophialum and observed a decrease in performance and weight gains and an increase in typical symptoms of fescue toxicosis in pasture with higher levels of A coenophialum contamination (See Hoveland et al. Agronomy Journal 75 pg 821-824 (1983) and Pedersen et al. New Zealand Journal of Experimental Agriculture 14 pg 307-312 (1986)).
The endophyte infection of tall fescue is very wide spread and the fungus is found in the fescue seeds. Thus, the fungal infection is carried over from one season to the next and has been found very difficult to eradicate. Current methods of endophyte control to prevent fescue toxicosis require fields to be chemically treated to destroy the fescue and then planted with other crop for 1,2 or more seasons to allow any residual seeds and their fungal contamination to be killed. Then the field must be planted with seeds specially grown to be free of endophyte contamination. Such procedures are obviously very labor intensive and costly and often will exceeds the savings resulting from the elimination of fescue toxicosis from pasture fed animals. Any savings that might result may then be defeated if the field is later reinfected with the fungus. Obviously the economical treatment of fescue toxicosis has long been a goal of breeders and growers of pasture fed livestock.
Ivermectin is a semi-synthetic member of the class of compounds known as avermectins which are macrocyclic esters which have been discovered to be highly potent antiparasitic agents for animals of both endo and ectoparasites. The compounds have further been found to be highly active as an agricultural pesticide and nematocides against insects which parasitize the aereal parts and roots of growing plants as well as stored agricultural products. Avermectin compounds however are not fungicidal and no reports of any fungicidal activity have been found.
SUMMARY OF THE INVENTION
This invention concerns the novel and unexpected utility of avermectin compounds, in particular ivermectin, to prevent the effects of fescue toxicosis in animals grazing on tall fescue infected with fungi. Thus, it is an object of this invention to describe such new utility and the avermectin compounds possessing it. A further object is to describe methods of administering such avermectin compounds to grazing animals. Further objects will become apparent from a reading of the following description.
DESCRIPTION OF THE INVENTION
Avermectin compounds have been discovered to significantly reduce or eliminate the toxic effects upon grazing animals, particularly ruminants, when tall fescue infected with fungi is ingested. The avermectin compounds are a series of compounds derived from the original avermectin natural products isolated from a fermentation broth and described in U.S. Pat. No. 4,310,519 to Albers-Schonberg et al. The avermectins are isolated as four pairs of compounds and the pair identified by B1a/B1b is the most preferred. The preferred 22,23-dihydro derivatives of the avermectins are disclosed in U.S. Pat. No. 4,199,569 to Chabala et al. and the 22,23-dihydro avermectin B1a/B1b pair of compounds in an approximately 80:20 mixture are most preferred and are known as ivermectin.
Other avermectin derivatives are useful in preventing fescue toxicosis such as the monosaccharide and aglycone derivatives disclosed in U.S. Pat. No. 4,206,205 to Mrozik et al; the acylated derivatives thereof such as those disclosed in U.S. Pat. No. 4,201,861 to Mrozik et al; the 13-deoxy aglycone compounds disclosed in U.S. Pat. Nos. Re. 32034 and Re. 32006 to Chabala et al; and the 4"-keto and 4"-amino compounds disclosed in U.S. Pat. No. 4,427,663 to Mrozik.
Additional compounds usable as in preventing fescue toxicosis are the milbemycin compounds disclosed in U.S. Pat. No. 3,950,360 to Aoki et al. and the oxime derivates thereof disclosed in U.S. Pat. No. 4,547,520 to Ide et al.
The preferred avermectin compounds for use in preventing fescue toxicosis are realized in the following structural formula: ##STR1## wherein the broken line indicates a single or double bond;
R 1 is H, ═O, loweralkanoyloxy or OH, provided that R 1 is present only when the broken line indicates a single bond;
R 2 is methyl, ethyl, isopropyl or sec-butyl;
R 3 is OH, OCH 3 or loweralkanoyloxy;
R 4 is H, OH, loweralkanoyloxy, α-L-oleandrosyloxy, 4'-(α-L-oleandrosyl)-α-L-oleandrosyloxy, 4'-loweralkanoyl-α-L-oleandrosyloxy, 4"-loweralkanoyl-4'-(α-L-oleandrosyl)-α-L-oleandrosyloxy, 4"-amino-4'-(α-L-oleandrosyl)-α-L-oleandrosyloxy, 4"-mono- or diloweralkylamino-4'-(α-L-oleandrosyl)-α-L-oleandrosyloxy,
and physiologically acceptable salts thereof.
The preferred milbemycin compounds for use as growth promotion agents are realized in the following formula: ##STR2## wherein the various R groups have the following meanings:
__________________________________________________________________________R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5__________________________________________________________________________H H CH.sub.3 CH.sub.3 OHH H CH.sub.3 CH.sub.3 OCH.sub.3H H C.sub.2 H.sub.5 CH.sub.3 OHH H C.sub.2 H.sub.5 CH.sub.3 OCH.sub.3OH ##STR3## CH.sub.3 CH.sub.3 OHOH ##STR4## CH.sub.3 CH.sub.3 OCH.sub.3OH ##STR5## C.sub.2 H.sub.5 CH.sub.3 OHOH ##STR6## C.sub.2 H.sub.5 CH.sub.3 OCH.sub.3H H CH.sub.3 ##STR7## OHH H C.sub.2 H.sub.5 ##STR8## OHH H i-C.sub.3 H.sub.7 ##STR9## OHH H CH.sub.3 CH.sub.3 NOR.sub.6H H C.sub.2 H.sub.5 CH.sub.3 NOR.sub.6H H i-C.sub.3 H.sub.7 CH.sub.3 NOR.sub.6__________________________________________________________________________
wherein R 6 is hydrogen or loweralkyl.
The term "loweralkyl" when used in the instant application is intended to represent those alkyl groups either straight or branched chain which have from 1-5 carbon atoms. Examples of such alkyl groups are methyl, ethyl, propyl, iso-propyl, butyl, sec-butyl, pentyl, and the like.
The term "loweralkanoyl" is intended to include those alkanoyl groups containing from one to five carbon atoms in either a straight or branched chain. Examples of such alkanoyl groups are formyl, acetyl, propionyl, butyryl, valeryl, and the like.
The "b" compounds, those with a 25-isopropyl group, are often not separated from the closely related "a" compounds with a 25-sec-butyl group since the physical and chemical properties of such compounds are similar, and as such the compounds are generally isolated as mixtures of the two compounds. Thus references in the instant application to "a" compounds such as B1a, A1a, and the like, are construed to define the pure compound as well as those which actually contain a certain proportion of the corresponding "b" compound. Alternatively, this representation of a mixture is sometimes done by referring to the compounds without designating "a" or "b" such as in the A1 or B2 compounds, or by separating the "a" compound from the "b" compound by a slash (/) such as B1a/B1b, B2a/B2b and the like.
The avermectin compounds can be used to prevent and treat the effects of fescue toxicosis in ruminant and non-ruminant animals such as sheep, cattle, goats, horses, that are pastured in fields of tall fescue. The active compound can be fed to the animal by incorporating it into the animal's feed or drinking water or it can be administered in a unit dosage form either orally as a drench, tablet, bolus or sustained release bolus or parenterally by injection or from a subcutaneous implant, or by a topically applied solution or suspension. The administration of the active compounds will allow the amimal to fully utilize the nutritional content of tall fescue, generally considered to be nutritionally adequate for maintenance and growth, without any of the manifestations of fescue toxicosis such as "fescue foot", "bovine fat necrosis" summer slump"and the like.
The active compounds can be administered to the animals at daily rates of from 0.004 to 2.0 mg/kg of body weight which may vary depending upon the particular animal being treated as well as the age and general physical condition of the animal. Preferably, daily dosages of from 0.04 to 1.0 mg/kg are utilized. When administered as part of the animal's feed or drinking water the active compound is present at rates of from 0.1 to 100 ppm which is determined to provide the appropriate daily amounts of the growth promotant compound.
The effects of an avermectin compound (ivermectin) in preventing symptoms of fescue toxicosis have been observed in field trials of cattle grazing on tall fescue highly infected (85%) with an endophytic fungus. The control animals showed classic signs of fescue toxicosis, reduced weight gain, poor coats, heat intolerance, fever and the like. The treated animals were given a sustained release bolus prior to grazing containing sufficient ivermectin for 120 days at from 0.04 to 0.06 mg/kg per day. The treated cattle gained an average of 39.6 kg more than the untreated cattle and further did not show any signs of fescue toxicosis. By visible examination, the treated cattle could be distinguished from the untreated cattle by observing their larger size, better coat and better disposition. In addition, the treated cattle had better appetites than the untreated cattle and grazed for longer periods of time, particularly in warmer weather when the effects of heat intolerance were becoming more apparent in the untreated cattle.
The test demonstrates the significant effects ivermectin and other avermectin and milbemycin compounds have on the elimination of the symptoms of fescue toxicosis.
In a further test, cattle were grazed on paddocks of tall fescue with high levels of endophyte fungal infection. After 120 days the cattle continuosly treated with ivermectin from a sustained release bolus gained an average of 28 kg more than the untreated cattle; about one-quarter of a kilogram per day over the controls. In this test the control cattle had a very low level parasite burden, thus any weight gains not observed would have to be due to fescue toxicosis, thus demonstrating the efficacy of the instant compounds in preventing toxic effects of such infected grasses.
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There is disclosed a method for the prevention of fescue toxicosis in grazing animals. Fescue toxicosis results from a grazing animal ingesting certain toxins present in or on the grass which can impair growth, reproductive performance, and is sometimes fatal. It has been discovered that the administration of ivermectin or related avermectin compounds is effective in reducing or eliminating the toxic effects of fescue endophyte ingestion.
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BACKGROUND OF THE INVENTION
This invention relates to an access manhole that is mounted in a storage or process tank or the like and, in particular, to a method of replacing an outwardly opening manhole cover with an inwardly opening manhole cover.
Many storage or process tanks and, in particular, older tanks, are equipped with manholes that include covers that open outwardly with regard to the tank. Typically, the cover is bolted to a flange that encircles the outside of a cylindrical manway. The term manway, as herein used, refers to a tubular member that is welded or otherwise joined to the tank to provide access into the tank. In the event the tank is pressurized or contains material that exerts an outwardly directed force against the cover, the bolts holding the cover in place must be strong enough to prevent unwanted opening of the cover. By replacing the outwardly opening cover with one that opens inwardly, any material forces that are exerted against the cover will help to hold the cover closed and will prevent material stored in the tank from collecting in the manway. Material that is collected in the manway produces unwanted spillage when the outwardly opening cover is removed and under certain conditions, can be hazardous. In addition, in process vessels, material which collects in the manway does not circulate freely within the vessel and thus, is typically over processed.
Replacing an outwardly opening manhole within a storage tank with a more preferred inwardly opening cover also has heretofore presented certain structural difficulties where the existing manway is removed from the tank and replaced with an entirely new manhole unit. Complete removal of the existing manhole can produce structural damage to the tank shell in and about the manway opening that oftentimes requires extensive repair to the tank. Furthermore, retrofitting a new manway to the repaired opening is sometimes difficult and can result in damage to existing tank coatings, linings or insulation.
DESCRIPTION OF THE RELATED ART
Turning initially to FIGS. 1 and 1A, there is shown a typical outwardly opening manhole which is constructed in accordance with the American Petroleum Institute Standard 650 welded steel tanks for oil storage. The manhole 10 includes a manway 12 that surrounds an opening 13 formed in the tank shell 15 that communicates with the interior 16 of the tank. The manway contains a cylindrical body section 17 having an inner flange 18 that is welded to the tank shell and an outer bolting flange 19. A cover 20 is secured to the outer flange by a number of bolts 22. A gasket 24 is generally mounted between the outer flange and the cover to prevent leakage from the tank to the surrounding environment. Although the manway is shown oriented vertically, the actual orientation could vary anywhere from vertical upward opening to horizontal to vertical downward opening.
As noted above, the outwardly opening manhole has certain disadvantages and it is oftentimes desirable to replace the outwardly opening manholes with ones that open inwardly. The conversion, however, can cause damage to a steel tank or weaken the tank, particularly where the existing manway is cut away from the tank shell and replaced with a completely new unit. In the case of a tank constructed of refractory bricks or the like, damage can also be extensive and the amount of repairs required to place the tank back in service rather costly. As will be described in detail below, the present invention relates to a method of converting an existing outwardly opening manhole with one that opens inwardly so that it causes little or no damage to either a steel or refractory tank. The present method of converting a tank is also more cost effective than those previously employed in the industry and results in a more secure and tighter fitting installation.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide an improved method of converting existing manholes in storage tanks or the like so that the cover of the tank opens inwardly rather than outwardly.
A further object of the present invention is to replace an existing manhole in a tank with a minimum of damage being done to the tank structure.
A still further object of the present invention is to reduce the amount of time required to replace an outwardly opening manhole in a tank with one having an inwardly opening cover.
Another object of the present invention is to provide an existing outward opening manhole with an inwardly opening cover that is capable of being positively sealed without undue retrofitting of the tank.
These and other objects of the present invention are attained by converting an existing manhole in a tank which has an outwardly opening cover mounted upon a bolting flange with a cover unit having an inwardly opening manhole. The conversion is accomplished by removing the cover form the bolting flange of the existing manway. A pair of spaced apart hinges for an inwardly opening cover are joined to a mounting flange and the mounting flange is attached to the existing bolting flange. An inwardly opening cover unit is rotatably mounted upon the hinges so that it closes against either the mounting flange or the rim of the manway.
BRIEF DESCRIPTION OF THE DRAWINGS
For a better understanding of these and other objects of the present invention, reference will be made to the following detailed description of the invention which is to be read in conjunction with the accompanying drawings, wherein:
FIG. 1 is a partial top plan view of a prior art outwardly opening manhole cover that is mounted upon a storage tank;
FIG. 1A is a section taken along lines 2--2 in FIG. 1;
FIG. 2 is a partial side elevation in section showing an existing outwardly opening manhole that has been modified to accept an inwardly opening cover;
FIG. 3 is a partial bottom view showing a further embodiment of the present invention;
FIG. 4 is a section taken along lines 4--4 in FIG. 3;
FIG. 5 is a partial bottom view of a still further embodiment of the present invention;
FIG. 6 is a section taken along lines 6--6 in FIG. 5; and
FIG. 7 is an enlarged partial view in section showing grouting packed in the space between the original manway and the insert.
DESCRIPTION OF THE INVENTION
Turning now to FIG. 2 there is illustrated an existing manhole 27 that is installed in a tank 28 which is similar in construction to that described in the American Petroleum Industry Standard 650. The manhole has been retrofitted to accept an inwardly opening cover assembly generally referenced 30. The cover assembly itself is well known and widely used throughout the industry and includes a dome shaped cover 31 that is pivotally mounted upon a beam 32 so that the cover can freely turn about the beam. A pair of spaced apart hinges generally referenced 34 are secured to the back of the beam and, as will be described below, the entire cover assembly is arranged to swing inwardly about the hinge pins 36. A bolt 37 is slidably contained at the distal end of the beam which, as will be explained below, is capable of engaging a mounting flange 38 associated with the manway to secure the cover in a closed position.
A locking mechanism 39 is also operatively associated with the beam and the cover which is adapted to pull the cover downwardly toward the manhole during closure. The locking mechanism includes a tubular member 40 that is pivotally attached at one end to the cover. The tube contains internal threads which mate with a thread rod 41. A hand wheel 42 is pinned to the distal end of the threaded rod to facilitate turning of the rod within the tubular member. A bracket 44 is pivotally supported in the beam and is pinned at 45 to the threaded rod. As can be seen when the beam is secured to the manway by the bolt, the cover can be drawn down by turning the hand wheel.
To convert the existing manway, the outwardly opening cover is removed from the bolting flange 19 of the manway and is replaced by a mounting flange 38. The mounting flange can be welded to the existing bolting flange or bolted thereto using the existing bolting hole arrangement. The mounting flange contains a central opening 46 therein through which access to the tank can be had. The opening in the mounting flange is slightly less in diameter than that of the opening 48 in the existing manway and a peripheral groove 49 is formed in the top surface of mounting flange about the opening 48. The groove is positioned in the mounting flange on the inside of the original manway opening. A seal 50 is mounted within the groove that contacts the rim 51 of the cover when it is closed against the mounting flange. A gasket seal 53 that is capable of functioning as a seal is mounted between the bolting flange 19 and the mounting flange 38 to further provide for a leak-proof closure about the manhole.
To close the manhole, the cover assembly is rotated downwardly about the binges so that the rim of the cover rests against the seal 50. The bolt 37 is then moved forward so that it closes under the mounting flange 38. The handwheel 42 is now turned to draw the rim of the cover 51 down into tight sealing engagement against the seal 50. To open the cover, the above described procedure is reversed. Because of the multiple hinged arrangement of the cover, the cover can be moved back and to one side of the access opening during the opening procedure to provide clear access to the tank through the opening in the mounting flange. As can be seen when the cover is closed and locked in place, material stored in the tank cannot collect in the manway. In addition, any internal pressure that is exerted upon the cover will help to retain the cover in the closed position.
With further reference to FIGS. 3 and 4, there is illustrated another embodiment of the present invention in which the existing manway 55 protrudes outwardly some distance from the shell 56 of the tank. The outer end of the manway terminates in a bolting flange 57 to which an existing outwardly opening cover unit 20, similar to that described above, is bolted. The cover, during conversion, is removed and a smaller diameter secondary manway, which will herein be referred to as insert 60, is inserted into the existing manway. The insert has an outer mounting flange 61 that mates with the bolting flange 57 of the existing manway and is secured thereto by welding, bolting or the like. A gasket 62 is mounted between the two flanges to provide a leak proof joint therebetween.
The axial length of the insert is greater than that of the original manway so that the distal end of the insert extends into the interior of the tank. An annular ring 65 surrounds the distal end of the insert upon which an inwardly opening cover assembly 35, as described above, is pivotally mounted. Although not shown, the bolt of the cover assembly is adapted to pass under the annular ring to secure the cover to the insert at closure. A peripheral groove 67 is formed in the top surface of the mounting flange. A seal 68 is mounted in the groove against which the cover closes. Here again, the hand wheel of the cover assembly is used to draw the cover down into sealing engagement with the seal to provide a leak-tight joint therebetween. Grouting 69 can also be placed within the gap between the existing manway and the insert to further seal the manhole in assembly.
A still further embodiment of the invention is illustrated in FIGS. 5 and 6. Here again, the existing manway 70 is rather elongated and passes through the shell 71 of the tank to provide an annular lip about the upper periphery of the manway. The original outwardly opening cover is removed from the outside bolting flange of the manway and a hinge assembly, generally referenced 75 is passed into the manway as shown. The hinge assembly includes an arcuate shaped foot 77 that is welded or bolted onto the existing bolting flange 78. A pair of spaced apart elongated stanchions 76 are secured to the foot and pass upwardly inside the existing manway in assembly. A pair of hinges 80 are mounted upon the distal end of the stanchions upon which an inwardly opening cover assembly 35, as described above is pivotally mounted. The cover is provided with a peripheral housing 81 that extends about the entire rim of the cover and contains a seal 82. In assembly, the seal is arranged to close against the upper rim of the existing manway to provide a leak-proof closure for the cover when the cover is secured and locked in place.
A latching mechanism 85 is provided to secure the cover in a closed position prior to locking it in place using the handwheel. The latching mechanism includes an elongated lever arm 86 that is pivotally mounted on the front of the cover beam. The lever arm terminates in a hook like appendage 87 that is arranged to pass under the bolting flange 90 of the existing manway to secure the cover in place at closure. A latch support brace 91 is provided to hold the lever arm in the latching position beneath the bolting flange. The brace is a two bar linkage comprising an upper link 92 pivotally mounted on the cover beam 32 and a lower link 93 that is pivotally mounted on the lever arm 86. The two links are rotatably joined at their distal ends so that the link can be brought into axial alignment at closure to prevent the latch from inadvertently becoming released after the cover has been secured in place.
Although the seal 82 is shown mounted in a peripheral housing 81, other suitable sealing arrangements may be similarly employed without departing from the teachings of the present invention. A further sealing arrangement is illustrated in FIG. 7. In this arrangement, the seal 100 is an annular shaped member that is oval in cross section and which contains a deep groove 101 that passes downwardly through the top of the seal. The seal is fabricated from a resilient rubber-like material. The diameter of the groove is coextensive with that of the cover rim 102 and the width of the groove is slightly less than the thickness of the cover. A tight interference fit is thus provided between the groove and rim so that the seal can be press fitted onto the cover. The seal thickness is sufficient so that a secure positive seal is formed against the upper rim of the existing manway at closure. Other suitable sealing arrangements may also be employed to establish a positive leak-proof joint between the cover and the cover receiving surface which can be located either on the mounting flange or the manway sleeve.
While this invention has been explained with reference to the structure disclosed herein, it is not confined to the details set forth and this invention is intended to cover any modifications and changes as may come within the scope of the following claims:
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A method of replacing an outwardly opening manhole cover that provides access to the interior of a tank or the like with an inwardly opening cover that includes the steps of removing the outwardly opening cover from the bolting flange of a tank installed manway and attaching a mounting flange to the manway bolting flange. A pair of hinges are connected to the mounting flange and an inwardly opening cover assembly is rotatably mounted on the hinges. The cover of the assembly is arranged to close and seal against either the mounting flange or the inner rim of the existing manway.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to the game of golf, and more specifically to a portable putting surface formed of a plurality of individual panels removably coverable with a continuous covering of simulated putting green. The heights of various portions of the panels and surface are independently adjustable so that upward and/or downward slopes may be provided, as well as sloping one or more of the panels to one side or the other to create a left and/or right slope along the path of the surface.
2. Description of the Related Art
The game of golf has enjoyed ever increasing popularity as the leisure time available to people has increased over the years. One of the attractions of the game is that while the basic principle is extremely simple, the various elements involved in the play of the game are nearly infinite, with practically every shot being unique. Many players tend to take the game quite seriously, and as a result, numerous devices have been developed to aid players, from training aids to more efficient clubs to higher performance golf balls to better shoes and other equipment, etc.
One type of device which has been developed is the simulated putting green, or a portion thereof, many of which have been constructed to be portable so a player may set up the simulated green for practice in a basement, recreation room, back yard, etc., and polish his or her putting game accordingly. However, as noted above, the natural lie of the terrain of a golf course leads to a practically infinite number of different situations which may be encountered by a golfer, and most such artificial devices do little to simulate some of the irregularities which can occur on a green, such as different slopes. While some earlier devices have seen the need to provide different slopes to simulate such conditions, such devices are generally cumbersome to set up, have limited or no adjustability, and/or have some other deficiency which makes their utility less than ideal.
Accordingly, a need will be seen for a portable golf putting surface which is formed of a plurality of separate sections with a continuous length of simulated golf green material removably installed thereover. The separate sections are each independently adjustable for height on each side thereof, thus enabling a user of the device to set up upward, downward, left, and/or right slopes with the present portable surface. The assembly and height or slope adjustment of the present device is accomplished quickly and easily in comparison to earlier devices of the related art, by various novel attachment and adjustment means. A discussion of the related art known to the present inventor, and its differences and distinctions from the present invention, is provided below.
U.S. Pat. No. 1,612,291 issued on Dec. 28, 1926 to George P. Jackson describes an. Indoor Golf Game having a raised area around the cup, and a ramp having a fixed slope leading to the raised cup area. The raised area is adjustable to provide varying slopes in different directions, but the adjustments are not accessible from the upper side of the device. The device is cumbersome to set up, as several flexible metal strips must be assembled with several adjustable jackscrews in a matrix, then covered with burlap and carpeting. No side rails are provided by Jackson for his putting area, whereas the present invention includes side rails which serve to connect the various panels together and also to hold externally accessible adjustment screws.
U.S. Pat. No. 3,508,756 issued on Apr. 28, 1970 to William A. Bedford, Jr. describes a Variable Surface Putting Device wherein a flexible sheet of material is resiliently suspended from a tubular frame. The frame includes a plurality of upstanding members, with the resilient connections between frame and flexible sheet being independently vertically adjustable on each of the upstanding members. The present portable putting surface comprises a plurality of individual panels temporarily overlaid with a continuous sheet of simulated putting green, whereas the surface of the Bedford, Jr. device is a thin, flaccid, freely suspended sheet of material. Moreover, Bedford, Jr. fails to disclose any side rails or other means of retaining a golf ball on the surface of his flaccid sheet, whereas the present invention includes such side rail ball retaining means.
U.S. Pat. No. 3,727,917 issued on Apr. 17, 1973 to George D. MacLean describes a Variable Contour Golf Putting Device comprising a plurality of hingedly connected panels each having a side rail affixed thereto. The hinges are attached to alternating upper edges of the side rails and alternating lower surfaces, so the device may be folded in a series of Z bends (accordion folds) for storage. The device is limited in comparison to the present invention, as it is relatively bulky when stored due to the height of the alternating side rails between every other panel when folded. Also, while MacLean provides means for the adjustment of the slope of various sections, the relatively rigid panels do not allow any lateral slope to be installed. Further, the dowels and blocks used to adjust the elevation of different panels provide relatively limited adjustment, compared to the infinitesimally fine adjustment provided by the present threaded adjusters.
U.S. Pat. No. 3,858,887 issued on Jan. 7, 1975 to Karl L. Wallin describes a Miniature Golf Course comprising a plurality of generally radially disposed courses extending from a central hole area. Wallin specifies that his floor members and side members are all extremely rigid and that plural lengths are rigidly affixed to one another to form a rigid and inflexible course, unlike the flexible nature of the present invention. Also, Wallin permanently affixes the side rails to each of his floor panels, unlike the present invention. Further, the adjustment means provided by Wallin is directed to leveling the entire course over uneven terrain, and thus teaches away from providing variable slopes.
U.S. Pat. No. 3,892,412 issued on Jul. 1, 1975 to Bonny B. Koo describes a Putting Practice Green comprising a plurality of separate pneumatically inflatable pads, each secured to a rigid backing board. No side rails are provided by Koo to retain a ball laterally on the surfaces. Moreover, no connecting means are provided by Koo to secure the panels together, as are provided by the present invention. The simulated green overlay is not continuous, as in the present invention, and adjustment of the slope is cumbersome and time consuming, as several inflatable containers are provided in each pad, each of which must be inflated or deflated as desired when adjustment is to be made.
U.S. Pat. No. 4,875,682 issued on Oct. 24, 1989 to Michael Paolillo describes a Practice Putting Game comprising a rigid central area with symmetrical ball receiving areas (not holes) at each end thereof. The device is more akin to a game than to a simulated putting green, as the ball receiving areas are each divided into three compartments, with the central compartment including a plurality of vertically suspended, swinging rods which must be deflected by the ball for the ball to enter. Each of the ends is sloped rearwardly, away from the central surface, but the slope is fixed to retain the balls better thereon. The carpeting material is permanently bonded to the rigid base material, instead of being temporarily placed thereon as in the present invention. Also, Paolillo does not provide any side rails along the central portion of his device, as he does not teach the provision of any slope therealong which would tend to deflect the ball to the side.
U.S. Pat. No. 5,002,280 issued on Mar. 26, 1991 to Burl D. Hines describes an Adjustable And Folding Putting Green comprising only two longitudinal sections hingedly secured together, with a third hingedly attached section pivotable to a lateral position. The two longitudinal sections are hinged together along their bottom edges, resulting in at least a slight gap or seam between the separate sections of artificial turf even when the sections are extended. Hines provides for the adjustment of the level of the device but the adjusting levers do not provide infinite adjustment, as provided by the present invention, and are disposed beneath the edges of the playing surface, unlike the present invention. Also, Hines fails to provide any side rails along the edges of his device, which side rails are a part of the present invention.
U.S. Pat. No. 5,171,016 issued on Dec. 15, 1992 to Charles J. Kamal describes an Apparatus For Practicing Putting And Chipping, comprising two separable shallow box-like panels with a simulated grass or turf material removably secured thereover. Side panels are included only about one half of the device, rather than along the entire sides of the device as in the present invention. Thus, the side panels do nothing to secure the two portions together. The slope is adjustable, but only to a limited extent, as the device provides sloped internal passages for automated return of the ball, and excessive downward slope toward the hole would cancel the ball return slope. Also, the slope adjustment is by blocks of fixed thickness placed under the device, rather than by infinitely adjustable jackscrews extending above the surface.
U.S. Pat. No. 5,318,303 issued on Jun. 7, 1994 to Samuel Kim describes a Putting Green With Adjustable Topography And Multi-Ball Return. The device comprises several permanently secured, foldable sections which cannot be disassembled from one another, as in the present invention. At least one embodiment discloses side members which are pivotally secured together to allow the device to be folded, but the side members are permanently attached to the playing surface and to each other, unlike the separable components of the present invention. Moreover, the Kim slope adjustment means requires an overhead frame to carry a series of cords therethrough, which cords are attached to various points on the playing surface and are pulled to raise different points as desired. The frame must remain in place during play for slope adjustment, and tends to obscure the player's view of the surface. The area above the putting surface of the present invention, is completely devoid of any overlying structure, unlike the Kim device.
U.S. Pat. No. 5,429,368. issued on Jul. 4, 1995 to Thomas R. Adams describes a Portable Practice Putting Device comprising a plurality of panels which are permanently secured together by hinges. The simulated grass overlay is permanently attached to the underlying panels, unlike the present invention. The device is relatively small, and includes means to restrict the lateral travel of the putter head in order to "groove" the putting stroke. This is the primary object of the Adams device, as the short and narrow length and lack of provision for any slope, limit the device insofar as any realistic putting practice is concerned.
Finally, British Patent Publication No. 2,121,297 published on Dec. 21, 1983 to Declan T. Carolan describes a Putting Practice Unit comprising a pair of panels permanently hinged together. The simulated grass surface carpet material is permanently attached to the two panels. The device may provide for adjustable slope by means of a series of pivotally attached pegs which extend from channels which are clipped to the edges of the board. A separate surface is provided for the golfer to stand on. While the support pegs provide essentially infinite slope adjustment along the length of the surface, they are disposed below the surface, rather than above as in the present invention for convenience of adjustment. Moreover, the Carolan putting unit does not include any side rails, as provided by the present invention.
None of the above inventions and patents, taken either singly or in combination, is seen to describe the instant invention as claimed.
SUMMARY OF THE INVENTION
The present invention comprises a portable practice putting surface having a variable slope which is adjustable to the left, right, up, and down in the direction of the putt. The surface is formed of a plurality of separate panels, with a single continuous length of synthetic grass or turf material removably overlying the panels. The surface includes removable side rails for each of the panels, with the side rails including slope adjustment means therein for the various areas of the surface.
Accordingly, it is a principal object of the invention to provide an improved portable putting surface which enables a golfer to adjust the slope of the surface defined by the panels of the device, to provide single or multiple variations in the slope as desired.
It is another object of the invention to provide an improved portable putting surface which slope adjustment is provided by a plurality of threaded adjusters extending through the side rails of the device, allowing slope adjustment to be made from above the surface.
It is a further object of the invention to provide an improved portable putting surface which panels are secured together by means of the connected side rails, which are in turn secured to the panels of the device.
An additional object of the invention is to provide an improved portable putting surface which provides for infinitesimally small adjustments in slope, as desired.
Still another object of the invention is to provide an improved portable putting surface preferably formed of plastic, but which may be formed of wood or other materials as desired.
It is an object of the invention to provide improved elements and arrangements thereof in an apparatus for the purposes described which is inexpensive, dependable and fully effective in accomplishing its intended purposes.
These and other objects of the present invention will become apparent upon review of the following specification and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an environmental perspective view of the present portable putting surface in use, showing the adjustment of the surface to provide a variety of different slopes therein.
FIG. 2 is an exploded perspective showing details of the various components of the present invention and their assembly.
FIG. 3 is a detailed side elevation view of the connection joint between adjacent side rails of the present putting surface.
FIG. 4 is an elevation view in section of the means for securing the side rails to the surface panels of the present putting surface.
FIG. 5 is an elevation view in section of the slope adjustment means of the present putting surface.
Similar reference characters denote corresponding features consistently throughout the attached drawings.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention comprises a portable putting surface, generally designated by the reference numeral 10. FIG. 1 provides a perspective view of the present putting surface 10 in use, showing its adjustment to provide variation in slope to add realism and challenge to putting practice when using the present surface 10. The present surface 10 may be assembled for outdoor use, with the slope adjustment means used to compensate for slope in the natural terrain, or may be used indoors, with the slope adjustment means used to provide slope to the surface as desired.
The putting surface 10 is formed of a series of separate flexible panels 12, as shown more clearly in the exploded perspective view of FIG. 2. The panels comprise a first panel 12a, a series of intermediate panels 12b, and an end panel 12c which includes a hole 14 therein for receiving a putted golf ball B when the present putting surface 10 is in use. Each of the panels 12 is identical to one another, with the exception of the end panel 12c containing the hole 14, having a left edge 16 (FIG. 4), an opposite and identical right edge 18, a forward edge 20, and an opposite rearward edge 22. Each of the panels 12 includes four upwardly extending side rail attachment fasteners 24, with two fasteners 24 closely adjacent the left edge 16 and another two fasteners 24 closely adjacent the right edge 18 of each panel 12. Each of the fasteners 24 has a generally T-shaped cross section (e.g., screw with screw head, etc.), for securing side rails (discussed immediately below) removably to the panels 12.
It will be seen in FIGS. 2 and 3 that any two adjacent panels 12 are not secured together directly to form the present putting surface 10. Rather, a plurality of removable side rails, comprising left side rails 26a and opposite right side rails 26b, are removably secured along the edges of the panels 12, with the rails 26a/26b in turn securing together to secure the panels 12 together as shown in FIG. 1. Preferably, the side rails 26a and 26b are mirror images of one another, due to the opposite attachment receptacle configuration formed in the different left and right side rails 26a and 26b.
Each of the side rails 26a and 26b includes a T-shaped slot 28 formed therein, with the size, shape, and positions of the slots 28 being configured to fit closely about corresponding fasteners 24, as shown in FIG. 4. The slots 28 preferably do not extend completely through the thickness of the side rails 26, but rather are formed only partially therethrough from the outer surface of each of the side rails 26. The side rails 26a/26b are installed respectively along the left and right edges 16 and 18 of each of the panels 12 by placing them immediately inwardly from the corresponding fasteners 24 and aligned therewith, and pressing the side rails 26a/26b toward the respective outer edges 16/18 of the panels to engage with and seat over the fasteners 24. The provision of the slots 28 only partially through the side rails 26 thus acts as a stop to preclude further outward movement of the side rails, in the event they are accidentally kicked, hit with a putter head or ball, etc. However, it will be seen that the slots 28 may be formed completely through each of the side rails, if desired, thus making at least all of the intermediate side rails identical without concern for left or right members.
Each of the side rails 26 has a first end 30 and an opposite second end 32, with the two ends 30 and 32 providing removable and pivotable connection means between different side rails 26. The first end 30 may comprise a round hinge member extending therefrom, with the opposite second end. 32 comprising a round socket configured to fit closely about the hinge member end 30 of another side rail 26, as shown in detail in FIGS. 2 and 3.
The rounded configuration of the two mating ends 30 and 32 allows two connected side rails 26 to pivot about an axis through the joint formed by the connected mating ends 30 and 32, as shown in FIG. 3. The male rounded hinge member ends 30 each encompass somewhat more than 180 degrees of arc from their extended side rail. end, with the semicircular socket 32 of each mating side rail encompassing slightly more than 180 degrees of arc. Any two of the mating end components 30 and 32 may be easily assembled to and disassembled from one another by sliding the male end 30 sidewards into and from the female or socket end 32. Yet, the slightly greater than 180 degrees of circular arc of the two components. assures that the end 30 cannot pull straight out from the mating socket end 32, thus securing any two of the side rails 26 together and allowing them to pivot or move arcuately relative to one another.
All of the side rails may be constructed as described above, if so desired. However, it will be seen that the socket and mating male rounded ends are not required for those ends which are adjacent the forward edge of the first panel 12a, and the rearward edge of the end panel 12c. In FIG. 1, these side rails, respectively side rails 26c, 26d, 26e, and 26f, are shown accordingly. However, the present invention will still function as described if only two types of side rails, i. e., side rails 26a and 26b, are provided, with those side rails also being used as side rails for the two end panels 12a and 12b, without their respective first and second ends being connected to other elements.
As noted further above, the present portable putting surface 10 is adjustable to provide different slopes as desired. The series of panels 12 may be adjusted by adjusting means installed through the side rails 26, to provide either forward, rearward, left, or right slope, or any combination thereof, as desired. The adjusting means comprises a plurality of steeply threaded jackscrews 34 or the like, with a corresponding number of mating threaded passages 36 formed generally vertically through each of the side rails 26 adjacent their first ends. The passages 36 may comprise inserts which are permanently molded or otherwise secured in place within the side rails, as shown in FIG. 5, or may be formed directly within the material comprising the side rails 26 as desired.
Preferably, the jackscrews 34 and mating passages 36 are formed with a steeply pitched thread to provide a relatively large advance per turn, as shown by the threads particularly in FIG. 5. As the present panels 12 are preferably on the order of three feet wide (other dimensions may be used), one inch of advance would provide a slope of 1:36, or slightly less than two degrees. Hence, a pitch of 1/3 or even 1/2 inch per screw turn would still provide sufficiently fine adjustment for the purposes of the present invention. Yet, the continuous advance possible by using such threaded components allows infinitesimally small increments to be made in adjusting the slope of the present putting surface 10. The jackscrews 34 may be provided with some form of handle means, e.g. the knurled knobs 38 of FIGS. 2 and 3 or the thumbscrew 40 of FIG. 5.
The present portable putting surface 10 is assembled for use by first installing the left and right side rails 26a and 26b (and 26c, d, e, and f, if those special end components are provided) to the fasteners 24 which are permanently installed along the left and right edges 16 and 18 of the panels 12. The side rails 26 are preferably installed from the inside of each panel 12, toward the. outer edge, with the slots 28 formed partially through each of the rails 26 serving as stops to preclude movement of the rails outwardly past the edges of the panels 12 once installed. An end rail 42 may then be installed across the end panel 12c having the hole 14 therein, with the attachment means being the same as that described for the other side rails 26. The end rail 42 retains. putted golf balls on the present surface 12, preventing their escape past the last or end panel 12c if the hole 14 is missed.
After the side rails 26 and end rail 42 are installed to the appropriate panels 12, the rails 26 are connected to one another by sliding the rounded knob or hinge 30 comprising the first end of each of the rails 26, laterally into the mating slots 32 of the second end of each of the rails 26, for each pair of rails 26 installed along the edges of each of the panels 12. (It should be noted that the rails 26 may be turned around end for end, if desired, as shown in FIG. 2.) The completed assembly leaves a slight gap 44 between adjacent panel ends, as shown in FIGS. 2 and 3, to allow space for the panel edges to approach one another as the slope of the panels is raised and the attached side rails 26 pivot about their mating ends 30 and 32.
The assembled surface is then covered with an overlay of simulated grass or turf material 46, such as Astroturf (tm) or other synthetic material providing a reasonable simulation of the closely mowed grass surface of a golf green. Other covering materials may be substituted, if so desired. The overlay 46 is preferably cut to have a width which fits closely between the opposite side rails 26a and 26b, and has a length sufficient to provide a continuous, unbroken span extending from the forward edge of the first panel 12a to the end rail 42 attached to the end panel 12c. The overlay includes a hole therethrough, congruent with the hole 14 of the panel 12c for receiving a putted golf ball.
At this point, a golfer may adjust the slope of the various panels as desired, by adjusting one or more of the various jackscrews 34 downwardly or upwardly through their respective passages or inserts 36, as desired. For example, the putting surface 10 of FIG. 1 has been adjusted to provide a downward left slope S1 by turning the right side jackscrews 34 down and into the right side rails 26b, as indicated by the relatively short length of the jackscrews 34 extending above the right side rails 26b along the central area of the surface 10, in comparison to the jackscrews 34 extending higher above the left side rails 26a in this area. A further examination of FIG. 1 will show that the jackscrews 34 along each connected length of side rails 26a and 26b are adjusted unevenly to provide additional variations in the slope of the surface, as desired by a golfer using the present surface 10.
In summary, the present portable putting surface 10 provides a most realistic means of duplicating a particular lie on a specific golf green, and/or for setting up varying slopes as desired to add challenge to practice putting. The variable slope adjustment means provided may also be used to level the surface in the event that it is assembled outdoors over uneven terrain. The ease of assembly of the present putting surface, without need for tools of any kind, assures that the surface will see reasonable use whenever a golfer has more than a few minutes of free time but cannot spare the time to visit his or her local golf course.
The present portable putting surface will also be seen to provide a most useful accessory for golf teaching professionals, in that the device may be used to teach an appreciation for different side hill lies and slopes when putting, for use indoors during inclement weather or when suitable conditions are not readily available. Thus, golf teaching professionals may make better use of their time when conditions are not suitable for outdoor play on the actual golf fairway and green surfaces.
In addition to the above, it will be seen that one or more of the side rail 26 or end rail 42 components or other obstacles may be placed atop the artificial turf overlay 46 as desired, to obstruct partially the direct line to the hole 14. Thus, the present portable putting surface may be configured to resemble many holes commonly seen on a miniature golf course, to provide a putting challenge for families during inclement weather, or for outdoor parties, etc., as desired.
The various components may be formed of virtually any suitable material, with the panels 12 and rails 26 and 42 being preferably formed of plastic for durability, light weight, and the required flexibility of the panels 12 to allow various slopes to be formed therein. Other materials, such as wood and metal sheet and extrusions, may be used if so desired. The relatively flexible nature of the artificial turf material 46 assists in smoothing out the relatively sharp breaks in contour and small gaps between adjacent panels 12, by curving smoothly over the adjacent panel. edges to simulate more accurately the gently rolling terrain of a real golf green. Thus, the present portable putting surface will provide golfers using the device with an economical and quite useful means of keeping their putting game sharp at all times.
It is to be understood that the present invention is not limited to the sole embodiment described above, but encompasses any and all embodiments within the scope of the following claims.
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A portable putting surface is formed of a plurality of separate panels each having opposite left and right side rails removably secured thereto. The side rails in turn have mating ends which are used to assemble the panels into a continuous surface. A continuous length of artificial grass or turf material (e. g., Astroturf, tm) is used to cover the panels to form a reasonably realistic putting surface. The side rails each include a slope adjusting screw, thus enabling the left and right sides of the surface, and different panels of the surface, to be adjusted independently of one another in infinitesimally small increments as desired. The present putting surface may be used to simulate side hill lies on a sloping green, and/or may be used to duplicate very closely the slope of any particular green, from any approach direction. The surface assembles and disassembles easily in a matter of a minute or so, and may be packed into an extremely small package for shipment or storage, as desired.
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RELATED APPLICATION
[0001] This Utility Patent Application for “Golf Putter Enhancement Device” filed on Feb. 10, 2007 is a Continuation-in-Part to U.S. Provisional Patent Application No. 60/772,273 filed Feb. 10, 2006 and claims the benefit of the priority date of that U.S. Provisional Patent Application. The aforementioned U.S. Provisional Patent Application No. 60/772,273 is hereby incorporated by reference in it's entirety for all purposes into this Patent Application.
BACKGROUND OF THE INVENTION
[0002] Through the history of golf, manufacturers of golf putters have tried to improve the features of their golf clubs. Features of improvement often have targeted issues affecting enhanced accuracy, such as ease of alignment of the club face to the ball and to the target, and enhanced weighting and balance to provide for a smooth firm stoke into the ball, through contact, and release of the ball from the club face. Some succeed better than others. Those putters that do offer improvement in most of these areas are usually quite expensive and fail to offer each golfer a wide range of adjustability so that they may tailor the putter to their own particular preferences. The golf putters that do not succeed very well in these areas have a definite performance dis-advantage and yet they too can be quite expensive.
[0003] Most putters which are sold do not offer any means to adjust the features affecting accuracy, nor the performance of the club, but are built with fixed characteristics. There have been built in the past, some golf putters which have built-in adjustability features, to allow a golfer to adjust the weighting and balance of the putter head. These units also are expensive, and do not allow the adjustable features to readily be transferred to a different putter, but are inherently designed into the particular golf club head itself.
[0004] This leaves most golfers with the dilemma of either buying an expensive new putter, which may or may not meet all their needs, or keeping the putter they have, with it's inherit limitations, and knowing they're at a disadvantage compared to other golfers who can afford to buy the latest, expensive, high tech equipment. Thus, there is a need for an inexpensive, after market, attachable device which can be mounted on a wide variety of putters and which will enable a golfer to technically improve and upgrade his putter to current industry performance standards while still allowing him the flexibility to make adjustments according to his own particular preferences.
SUMMARY OF THE INVENTION
[0005] In view of the limitations now present in the prior art, the present invention provides a new and useful way to upgrade a golf putter where said invention is universally usable and more versatile in operation than known apparatus of this kind.
[0006] The purpose of the present invention is to provide a new, inexpensive, universal, attachable golf putter performance improvement device which is not apparent, obvious, or suggested, either directly or indirectly by any of the prior art apparatus. An easily attached, universal and inexpensive performance enhancement device for a wide variety of existing golf putters, which are limited in their performance specifications and options. This device does not require any modifications to the existing golf putter to which it will be attached and was designed so that it may be use during the actual playing of a round of golf. The device is designed to mount in front of and on top of an existing golf putter by means of adhesive tape between the device and the existing golf putter, and by squeezing or clamping the existing golf putter between the backside of the face of the device and a set screw mounted in a tube or cylinder on the underside of the device. The face of the device replaces the face of the existing golf putter and becomes the new striking surface, which is now softer and provides improved audio and tactile feedback on centered and off centered strikes of the golf ball. The top of the device approximates the width of an actual golf ball and extends rearwards away from the face and provides a flat surface for an alignment aid and also moves the center of gravity back away from the face and upwards from the sole of the existing golf putter. The alignment aid on top of the device consists of a raised rib which is centered and extends from the front to the back of the device. This rib is bordered by four raised white, half circles which offer a three dimensional visual image of two white balls split in half by a bold line that extends from the end of the device towards the actual golf ball. The underside of this top piece houses the pre-mentioned set screw in a tube which is either threaded or has threaded inserts at both ends. The threaded end near the back end of the device is used to house various length weighted cap screws which alter the overall weight, swing weight and position of the center of gravity of the existing golf putter. All these improvements and options are considered industry standards for improving a putter's performance and consequently the putting skills of golfers.
[0007] The present invention generally comprises an “L” shaped body, made of a somewhat rigid, thin and lightweight material, which mounts in front of and on top of an existing golf putter. The front section or leg of the invention is slightly smaller in height, width and length of the face of the average existing golf putter and mounts in front of and replaces such face. The top section or leg is approximately the width of an actual golf ball and extends rearward, away from the face for approximately the length of two actual golf balls with appropriate spacing in between and at both ends. This top section has a raised rib on top of it which is centered and travels from the front to the rear of the device. Along either side of this rib are two raised half circles, which makes four in total. The two half circles on one side of the rib are directly opposite the two half circles on the other side of the rib. These circles can be painted white or have white half circle labels adhered to them or they may be reduced in height to allow a white half circle of plastic to be glued to them, in which case they must be reduced in height to allow for the thickness of the white plastic and glue. Whichever means is used, their purpose is to give a golfer looking down at this device a three dimensional image of two full white circles (which simulate two actual golf balls) with a bold alignment or target line running thru the middle of these circles and pointing at the target. The surfaces of the front and top of the device may be textured slightly and/or painted a dull, flat color to reduce glare into the golfer's eyes. On the underside of the top section is a centered, cylindrical tube referred to as the mounting tube which is threaded or has threaded inserts at both ends and sits approximately 0.625 inches back and away from the backside (or cavity) of the face of the existing golf putter. The other end of the tube is indented slightly from the very end of the top section. This tube serves two functions. The front end near the face carries an internal set screw which screws forward towards the backside or cavity of the existing club and clamps the existing club between itself and the backside of the face of this device. This screw is accessed thru the rear end of the tube with an appropriate wrench. This clamping force is reinforced or boosted by double sided adhesive tape which is applied between the face of the existing club and the backside of the device's face. After the set screw has been tightened properly so that the top piece of the device is parallel to the sole of the existing club and at the same time perpendicular to the shaft or hosel of the existing club, the rear end of the mounting tube can now accept different length weighted screws to affect the weight distribution and center of gravity of the existing club, or a V shaped device with two threaded, cylinder shaped legs may be attached at that same point. The V shaped tube will also accept different length weighted screws at the end of each leg in order to affect the perimeter weighting of the putter.
[0008] The foregoing has outlined, in general, the physical aspects of the invention and is to serve as an aid to better understanding the more complete detailed description which is to follow. In reference to such, there is to be a clear understanding that the present invention is not limited to the method or detail of construction, fabrication, material, or application of use described and illustrated herein. Any other variation of fabrication, use or application should be considered apparent as an alternative embodiment of the present invention.
FIELD OF THE INVENTION
[0009] This invention relates generally to the field of apparatus for a golf club. Moreover it pertains specifically to an apparatus for attachment to existing golf putters in order to improve performance features, and increase accuracy and consistency. Such performance features to increase accuracy and consistency include, but are not limited to: target alignment, variable movement of the center of gravity, variable adjustment of the static weight, variable adjustment of the swing weight, variable adjustment of the perimeter weighting and softening the striking face, all of which will enable a golfer to improve their putting skills.
OBJECTS OF THE INVENTION
[0010] A principal object of the present invention is to provide an easily attached device which upgrades the performance specifications and options of existing golf putters and that will overcome the deficiencies of the prior art devices.
[0011] Another object of the present invention is to provide a performance and option upgrade device that is inexpensive, fits many existing golf putters and is simple to use.
[0012] Another object of the present invention is to provide a performance and option upgrade device that can easily be attached and removed from an existing golf putter without making any modifications to the existing golf putter.
[0013] Another object of the present invention is to provide a performance and option upgrade device that will variably move an existing golf putter's center of gravity back away from it's striking surface and upwards away from it's sole.
[0014] Another object of the present invention is to provide a performance and option upgrade device that will allow variable adjustment of an existing golf putter's static weight and swing weight.
[0015] Another object of the present invention is to provide a performance and option upgrade that will allow variable adjustment of an existing golf putter's perimeter weighting.
[0016] Another object of the present invention is to provide a performance and option upgrade device that will offer space on top of the putter for an alignment aid, including but not limited to, a three dimensional aid.
[0017] Another object of the present invention is to provide a performance and option upgrade device that eliminates glare and reflection into a golfer's eyes.
[0018] Another object of the present invention is to provide a performance and option upgrade that can be permanently mounted and adhere to the United States Golf Association's rules of golf club design and conformity.
[0019] It is intended that any other advantages and objects of the present invention that become apparent or obvious from the detailed description or illustrations contained herein are within the scope of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] The following drawings further describe by illustration the advantages and objects of the present invention. Each drawing is referenced by corresponding figure reference characters within the “DETAILED DESCRIPTION OF THE INVENTION’ section to follow.
[0021] FIG. 1 is a perspective view of the front (or face) and top of a golf putter enhancement device according to the present invention.
[0022] FIG. 2 is a bottom and side view of a golf putter enhancement device according to the present invention.
[0023] FIG. 3 is a bottom and rear view of a golf putter enhancement device according to the present invention.
[0024] FIG. 4 is a side view of a golf putter enhancement device in position to be attached to an existing putter.
[0025] FIG. 5 is a side view of a golf putter enhancement device partially attached to an existing putter.
[0026] FIG. 6 is a top view of a golf putter enhancement device completely attached to an existing golf putter.
[0027] FIG.7 is a cutaway view of a golf putter enhancement device showing nuts and bolts.
[0028] FIG. 8 is a top view of a golf putter enhancement device completely attached to an existing golf putter, showing an added wing weight.
[0029] FIG. 9 is a bottom and rear view of a golf putter enhancement device according to the present invention, showing an added wing weight.
[0030] FIG. 10 is a cutaway view of a golf putter enhancement device wing weight showing threaded inserts.
[0031] FIG. 11 is a front view of a golf putter enhancement device according to the present invention, showing an additional trim ring.
DETAILED DESCRIPTION OF THE INVENTION
[0032] A golf putter enhancement device of the present invention is generally designated 1 . The device 1 , shown in FIG. 1 , is made as a universal attachable device to enhance the performance of a golf club. The device 1 in a preferred embodiment is configured to be fitted onto the head portion of a golf putter. Since the device 1 as shown is designed to quickly and simply attach to any number of golfing putters, it can serve as an aftermarket kit to enhance an otherwise ordinary golf putter. The device 1 is made to attach to a wide variety of existing golf putters without the need to alter the existing putter such as without drilling holes or tapping threads. Thus the device is useful for enhancing the play of a golfer who has several putters, or for a golfer who wants to enhance the characteristics of an existing favorite putter.
[0033] As shown in a preferred embodiment in FIG. 1 , the body of the device 1 is basically “L” shaped, with a front end 2 , and a back end 3 , and with a top side 4 , and a bottom side 5 . The front end 2 can be described as having an outside 6 and an inside 7 . The device as shown is made with a bend 8 of approximately 90 degrees at the top side 4 of the front end 2 , where the bend 8 can be described as running between between a top piece 12 and the front face piece 13 . The device 1 as shown can further comprise an alignment rib 14 running down the center of the top piece 12 , from front 2 to back 3 , where the rib 14 serves as an alignment aid, and also serves to stiffen the top piece 12 . As a further means to enhance alignment, a plurality of half circles 15 can be included along either side of rib 14 , such as shown in FIG. 1 with two half circles 15 placed on each side of the rib 14 . The half circles 15 are preferably placed with a slight spacing between each half circle 15 , and outside each half circle 15 , such as to enhance the visibility of the alignment enhancement means. The half circles 15 are designed as an alignment enhancement means, serving in this embodiment to replicate the visual image of a plurality of golf balls aligned with a golfer's actual target golf ball, where the alignment enhancement means is designed to assist the golfer in visualizing the preferred direction of the golfer's stroke for hitting a ball towards a desired direction. Similarly, the described alignment rib 14 can be built into the inventive device 1 as an alignment enhancement means, such that the alignment rib 14 as described is designed to assist a golfer in visualizing and aligning the golf stroke in the desired direction. Obviously, the rib 14 and/or the half circles 15 , as described can be used singularly or together in various particular embodiments of the inventive device. Other alignment means may similarly be employed within the scope of the invention which are designed to assist a golfer in aligning the golf stroked in a desired direction. Obviously, full round circles (not shown) could similarly be used as a golf club alignment means incorporated into a golf club enhancement device 1 .
[0034] In a simple embodiment of a golf club enhancement device 1 , an alignment rib 14 , and/or a plurality of half circles 15 , and/or other alignment enhancement means, can be built flush into the top 4 surface of the top piece 12 of the device 1 . However, in a more preferred embodiment as depicted in FIG. 1 , an alignment rib and a plurality of half circles can be mounted onto the top 4 of the surface of top piece 12 of the device 1 , such that they are raised above an otherwise nominally flat surface top 4 of the top piece 12 , presenting a three dimensional visual enhancement means. This usage as described herein of a three dimensional, raised alignment rib 14 as a golf club visual enhancement means may well be useful and novel in of it self within the realm of useful golf clubs. Similarly, the usage as described herein, of a plurality of white half circles 15 , (or full round circles, not shown), which are raised to form a three dimensional raised flat surface above the otherwise nominally flat top 4 surface of a golf club may be novel in of itself within the realm of useful golf clubs.
[0035] As shown in FIG. 2 and in FIG. 3 , the bottom side 5 of top piece 12 can be made with an attaching mechanism 9 to attach the device I to a golf putter. In one preferred embodiment, as shown in FIG. 2 , an attaching mechanism 9 can be made using a threaded mounting tube 16 which can be molded onto the bottom 5 of the top piece 12 , or otherwise attached to the device 1 . Such a threaded mounting tube 16 can be made with threads molded directly into the inside of the tube 16 , such as with plastic molding or metal molding methods, or alternatively, one or more separate threaded element(s) 17 can be inserted and affixed inside the mounting tube 16 . A threaded mounting tube 16 can be used both for attaching the device 1 to a golf putter, using a threaded clamping bolt 18 , and also can be used to affix one or more threaded weighting elements 19 to the golf enhancement device 1 . If desired, rather than making an attaching mechanism 9 with a long continuous threaded mounting tube 16 , a mounting mechanism 9 can be made with a threaded element 17 towards the front 2 of the device, to receive and secure a clamping bolt 18 , and additionally with weighting element receiving threads 20 affixed towards the back 3 of the device 1 . A weighting element 19 can be easily and quickly removed and exchanged for a different sized weighting element 19 of any reasonable amount of desired mass which is useful for enhancing the swing weight, center of gravity, and momentum characteristics of a golf putter. A weighting element 19 can be made comprising a simple metal bolt for example, and various size bolts may be used interchangeable to quickly and inexpensively adjust and enhance the characteristics of a desired golf putter.
[0036] With this preferred method of attaching threaded weighting elements 19 to the back 3 of the device 1 , such weighting elements 19 can be made of various desired amounts of weights, where said various weights can be readily interchanged, to alter the effective weighting of the putter. Furthermore, with this method of using a threaded mounting tube 16 along with weighting elements 19 , the effective swing and momentum of the putter can be fine tuned, by adjusting a weighting element along the threaded element 17 from the front 2 to the back 3 of the device 1 .
[0037] Thus by building the device 1 equipped for affixing the inventive device 1 in a removable and nondestructive manner to a golf club, such as by using a clamping type of attaching mechanism 9 as described above, and by making the device 1 such that various weighing elements 19 can be interchanged within the device, as described above, the inventive golf putter enhancement device presented herein provides a unique advantage over club weighting methods which require a specialized putter, or require drilling and thread tapping into the club itself.
[0038] As would be obvious to those skilled in the arts, other effectively similar methods could be used to attach the device 1 to a golf club, and also other methods could be used to attach weighting elements 19 to the device 1 . For example, another method for attaching an attachable golf club enhancement device 1 to a golf club, would be with a cantilever type clamp (not shown). Similarly, glue, tape, suction cups, or simple spring clip mechanisms could be used, along with any number of comparable attaching methods which are known or could be devised by those skilled in the arts. As shown in FIG. 2 , a strip of double sided sticky tape 11 can be useful in conjunction with a mechanical clamping attaching mechanism 9 , to help secure the device in position on the club to help prevent shifting of the device 1 relative to the attached club, through constant play and transport.
[0039] Preferably, in a first embodiment, the golf club enhancement device 1 would be made to be removably attachable to a golf club head, so that the device 1 could be used for instance, on a first putter one day, then removed, and attached to a second different putter another day, depending upon the golfers desire, or golfing conditions for a particular course or weather conditions. In a second embodiment, a golf club device as described here could be permanently affixed to a single particular golf club, such as where a golfer wanted that particular club to conform to golfing regulations, such as USGA regulations which might require all parts of a putter to be permanently affixed. If a user of the device 1 desired to make the attachable golf club enhancement device 1 permanently affixed to a particular golf club, attachment methods might be broadened to include permanent glue, or epoxy, or soldering or welding, or other known methods of attachment.
[0040] The device 1 can be inexpensively manufactured using any of a variety of well know methods. The material used should be somewhat rigid, yet thin and lightweight, including but not limited to, plastic or aluminum. ABS plastic can successfully used, and is very inexpensive and easy to work with. In a preferred embodiment, the body portion 12 should be lightweight, so that most of the weight of the device is placed well back from the face of the putter to enhance the momentum characteristics. The device body 12 and face 13 could be injection molded, milled from a solid block or created by bending of sheet stock. The thickness of device body 12 and face 13 would vary depending on the strength and weight of the material. In preferred embodiment the device is molded from black plastic as one piece and external hardware such as threaded inserts 17 and 20 are added to mounting tube 16 . The top side 4 of top piece 12 and the front end 2 of the front face piece 13 are also preferably textured during the injection process to reduce glare in the golfer's eyes. This could also be done by painting these surfaces with a dull or flat color.
[0041] In FIG. 4 , a perspective view of top piece 12 and front piece 13 is shown along with rib 14 and half circles 15 . Front face piece 13 is intended to fit over the front of an existing golf putter and replace such front with the new striking surface. Since there are many different size putters available, in one embodiment, front piece 13 's dimensions have been created to be 4 inches wide at it's widest point, which is 0.1875 inches up from the bottom edge and 1.0625 inches high at it's highest point, which is in the center, top portion of front piece 13 . The thickness of front piece 13 is 0.125 inches. As the bottom edge of front piece 13 moves outward, left and right from the center, it rises slightly to reflect the gradual curve or radius that most existing putters have to their soles. At the 4 inch wide point the sides edges of front piece 13 move upwards 0.75 inches and slightly inward 0.375 inches, again, to reflect the shape of most existing putters. As these sides rise upwards and reach the plane of top piece 12 's bottom edge they move inwards horizontally until they junction with top piece 12 .
[0042] Top piece 12 extends (horizontally) from it's junction bend 8 , with front piece 13 , away from what would be the front of the putter towards what would be referred to as the rear of the putter. The corner edge bend 8 where front piece 13 and top piece 12 meet has a curve to it with a radius of 0.0625 inches, for aesthetic purposes. Rib 14 's front end starts on this plane and also has a 0.0625 radius to it, so that it may blend into front edge 13 . The width of top piece 12 is 1.75 inches. This dimension reflects the average width of the cavity or hollow on the backside of most existing putters and their attempts to visually frame the outside edges of an actual golf ball. The basic thickness of top piece 12 is 0.125 inches, except for rib 14 and half circles 15 which extend 0.125 inches above top piece 12 . In this embodiment, half circles 15 are painted white or labeled white. Another option is to mold them slightly thinner, perhaps 0.0625 inches thick, and glue a white plastic half circle on top of the black plastic half circles. The two combined would still be level with rib 14 at 0.125 inches above top piece 12 . All half circle 15 's have a 0.75 inch radius. Top piece 12 extends rearward away from front piece 13 for 3.625 inches. This dimension allows a 0.25 inch space between the edge of front piece 13 and the first set of half circles 15 , 0.25 inches between the first set of half circles 15 and the second set of half circles 15 and 0.125 inches between the second set of half circles 15 and the back edge of top piece 12 . Rib 14 , which stiffens top piece 12 and separates half circles 15 is 0.125 inches wide. All dimensions relating to top piece 12 are variable averages depending on a number of things: the length and width desired for the alignment features, the total weight desired to be added to the existing putter, the degree of movement desired in relocating the center of gravity, etc. All these dimensions can differ yet still reflect the purpose of this invention.
[0043] The device 1 can be made in any reasonable desired size useful for playing golf, yet possible dimensions of one useful embodiment shall be given here for a detailed example for building the device 1 . FIGS. 2 and 3 illustrate the bottom 5 of top piece 12 and the backside 7 of front piece 13 . In this embodiment, the bottom 5 of top piece 12 has for an attaching mechanism 9 , a molded tunnel or tube running along it's center line. This is referred to as mounting tube 16 . It can be made “U” shaped with a 0.3906 inch diameter hole running from one end to the other. The center of this hole is 0.375 inches below the bottom 5 of top piece 12 .
[0044] FIGS. 2 and 3 illustrate the bottom of top piece 12 and the backside of front piece 13 . In one embodiment, the bottom of top piece 12 has a molded tunnel or tube running along it's center line. This is referred to as mounting tube 16 . It's made “U” shaped with a 0.3906 inch diameter hole running from one end to the other. The center of this hole is 0.375 inches below the bottom of top piece 2 . Mounting tube 6 has 0.3125 inch threaded inserts 7 inserted at each end.
[0045] In another, later developed preferred embodiment, as shown in FIG. 7 , mounting tube 16 has affixed a nylon threaded nut 22 which serves as providing the weighted element receiving threads 20 towards the back 3 of mounting tube 16 , and another nylon threaded nut 23 towards the front 2 of mounting tube 16 to serve as threaded element 17 used to affix a threaded clamping bolt 18 . Nylon nuts are used to reduce the basic weight of the device, so that a broader weighting range towards a lighter range, can be achieved overall. Clearly, various types of similar methods can be devised to accommodate a clamping bolt 18 and to removably affix a weighted element 19 .
[0046] In this useful embodiment detailed example, the outside dimensions of the “U” shaped mounting tube 9 are on the order of 0.5 inches across the base (connecting to top piece 12 ), 0.625 inches high and a 0.5 inch radius to the curve of the “U” shape. The length of mounting tube 16 is 2.5 inches. It is situated 0.75 inches back and away from the backside of front piece 13 and indented 0.25 inches from the back edge of top piece 12 . The purpose of mounting tube 16 is two fold. First, it is the main means of attaching the device to an existing golf putter. Using the proper hex key or allen wrench, a 1×0.325 inch set screw 18 is screwed into the threaded insert 20 at the back of mounting tube 16 until it travels thru the tube 16 and reaches the threaded insert 17 at the front end of mounting tube 16 . It is then screwed thru this insert 17 until it makes contact with the backside or cavity of the existing putter to which it will be attached. This will result in the existing putter being squeezed or clamped between the backside 7 of front piece 13 , and set screw 18 . After set screw 18 is tightened properly, mounting tube 16 is able to accomplish it's second purpose: adding more overall weight, which will increase the swing weight and move the center of gravity of the putter further backwards 3 and upwards 5 . This is accomplished by screwing in various length and weight cap screws 19 , which also have 0.3125 inch threads, into the back threaded insert, also referred to as the weighted element receiving threads 20 at the back of mounting tube 16 . With cap screws available in an assortment of different lengths and weights a golfer should have quite a few different “feels” (light, medium, heavy) he can assign to his putter. A slotted head threaded set screw could similarly be used rather than an allen set screw for the clamping bolt 18 .
[0047] FIG. 4 illustrates device 1 about to be mounted to a typical existing golf putter, and FIG. 5 illustrates device 1 attached to a typical existing golf putter. To reinforce the clamping force of threaded mounting bolt 18 a 0.75×3 inch strip of double sided adhesive tape 11 can be applied to the backside 7 of front piece 13 . Just before device 1 is placed in front of and on top of existing putter the protective cover of tape 11 is removed. Device 1 is then moved downward until the bottom side 5 of top piece 12 contacts putter. Device 1 is then pushed rearwards until tape 11 contacts the face of putter. Both movements are done while keeping device 1 generally centered between the toe and the heel of putter. After tape 11 has contacted putter face, pressure is applied to front piece 13 by hand from one end to the other for a few seconds to ensure a good adhesive bond has been created. Finally, the threaded mounting bolt is tightened thru the backend 3 of mounting tube 9 until it is seated into the cavity of putter. Due to most existing golf putters having anywhere from 3 to 5 degrees of loft designed into their face, device 1 's top side will not be perpendicular to putter's hosel when first positioned for attachment, as shown in FIG. 5 . Therefore, threaded mounting bolt 18 should continue to be tightened towards cavity on the back of the putter until top piece 12 is perpendicular to putter shaft. This will ensure that top piece 12 is horizontal and level in relation to the putting surface or green and that a sufficient amount of clamping force has been applied between device 1 and putter. When these steps have been completed a golfer looking down at his putter will see a view similar to that shown in FIG. 6 . At this point it is up to each individual golfer to experiment with inserting different weighting elements 19 into backside insert 20 and arrive at a weighting “feel” that's comfortable and works for them.
[0048] As another slight variation of manufacturing the device 1 , a mounting tube 16 can be made with two pieces, as shown in FIG. 7 . A first piece of mounting tube 16 would be molded or affixed onto bottom side 5 of the top 12 of device 1 as shown, to accommodate the placement of threaded nylon nuts 22 and 23 . A second cap piece 21 is made to fit on to complete the enclosure of threaded, and to hold the nuts 22 and 23 firmly in place. By making the mounting tube 16 in this two part manner, a threaded clamping bolt can also easily be inserted into place during manufacture as depicted in FIG. 7 . A nylon or other plastic material bolt is useful as a light weight choice for clamping bolt 18 . The cap piece 21 can be attached to the base of mounting tube 16 with glue or by sonic welding.
[0049] Various types, sizes and shapes of weighting elements 19 can be used in conjunction with the inventive golf club enhancement device 1 . Modern golf putter technology often includes the usage of a significant amount of weight to be placed towards the far back 3 of a putter. Also, modern putters often employ weighting styles which put significant amounts of weight spreading horizontally out away from the striking center of the putter face, such that back-weighting is effected behind the toe and the heel of the putter, in order to prevent twisting of the putter head if a golf ball is struck off of the horizontal center of the putter face.
[0050] A shown in FIGS. 8 and 9 , the inventive device 1 can employ a V-shaped wing weight 32 in order to enhance the quality effect of the stroke of a putter to which the device is attached, by employing a significant amount of back weighting and significant amounts of horizontal weight spreading to prevent twisting of the putter in case of an off centered strike. The wing weight 32 and other useful weighting elements 19 can be designed to bring the weighting center of gravity upwards, to produce less “hop” to a struck ball.
[0051] FIG. 9 shows a wing weight 32 inline to be connected to the device 1 . the wing weight 32 as shown, has two wings 33 placed one on each side of the horizontal center of the wing weight 32 . At the end of each wing farthest from the horizontal center of the wing weight 32 , a wing weight threaded portion 34 can be added, to accommodate a weighted element 19 , where such weighted element 19 can be identical to the weighted element 19 used in the weighting threads 20 described above, and similarly, weighting elements 19 used here can be of various desired mass. The wing weight 32 can be simply and removably connected to the back 3 of the device 1 using a wing weight attachment portion 35 . Such an attachment portion 35 can comprise a through hole from front 2 to back 3 , and may optionally include wing weight attachment threads 36 . A simple bolt which is used as a weighting element 19 can be used to connect the wing weight 32 to the weighted element receiving threads 20 of the device 1 , thus making the device very conveniently adjustable and modular in style.
[0052] A useful way to manufacture such a wing weight 32 is depicted in a cutaway diagram shown in FIG. 10 . The wing weight 32 is made with three molded parts, including the wing weight base 37 , and two wing caps 38 , which are designed to fit onto a cutaway version of the wing weight base 37 , as shown. This manufacturing method allows the wing weight threaded portions 34 to be built using wing weight threaded inserts 39 , which can be placed into the cut away portion of the wing weight base 37 and then sealed into place such as by gluing or sonic welding of the wing caps 38 . Such wing weight threaded inserts 39 can be preferably made of a threaded brass cylinder for example, to make them strong and durable, and to add weight into this desired region.
[0053] It should be noted, that according to some golf tournament rules, a tournament legal putter must have a nominally flat face which is used to strike the ball, where only a slight amount of texturing and/or grooves are allowed. One useful and novel feature of the inventive device 1 described herein, is that the device as designed provides a nominally flat striking face 13 which also serves as part of the method and apparatus for attachment, when a clamping type connection method is employed, as described herein.
[0054] However, since the device is designed as a useful universal aftermarket kit to attach to many types and shapes and sizes of putters, there arises the situation where a single size and shape for the front face 13 of device 1 will not simply fit all existing putters that a golfer may wish to use. Although many golfers do not need to compete in USGA tournaments, other golfers will. The device 1 as described in the above specified example listing preferred embodiment dimensions will be useful for many putters, although some putter faces may be slightly larger than the face 13 of the device 1 as described. Thus an additional component may be added to the device 1 , called a trim ring 40 , as pictured in FIG. 11 . The trim ring would be included in a golf club enhancement device kit and can optionally be added to the device 1 by the golfer, or can be fitted by a golf club maintenance shop, or other handy person skilled in the art. The trim ring 40 is made of the same material as the front face 13 and is the same thickness as the front face 13 . As shown in FIG. 11 , the inner portion 41 of the trim ring 40 is made to fit exactly around the facial circumference of the front face 13 of the device 1 as provided. The trim ring 40 can be fitted to the club after the device 1 is attached to the golf club head. It can be placed for measurement fitting tightly around the front face 13 , and then marked and trimmed to size, to fully cover the front face of the desired putter. After cutting to size, the remaining desired sized portion of the trim ring 40 can then be attached to the club face, such as with epoxy cement. The resultant device 1 now includes the basic device 1 as described above, along with the affixed trim ring 40 portion attached.
[0055] It should also be noted, that another feature of the inventive device 1 is that an enhanced ball contacting surface can be enabled with the device, depending upon the usage of a selected material with which the front face 13 of device 1 is constructed. The front face 13 can be made with a soft material to add more “touch” of “feel” to the putter, and to give a desired action to the ball upon contact. Also the front face 13 of the device 1 can be made with texture or slight grooves to add more feel and control of the ball upon contact with the front face 13 surface of a golf club enhancement device 1 . A plurality of layers of material could also be employed in manufacturing the front face 13 of the device 1 .
[0056] Obviously, many other effectively similar manufacturing methods, materials, and embellishments for weighting, attachment, and alignment can be used to create various embodiments of the inventive golf club enhancement device which shall be construed to be within the intended scope of the description and claims of this patent.
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An easily attached, universal performance enhancement device for existing golf putters. The invention comprises an “L” shaped body, made of a rigid, lightweight material. The device is designed to mount in front of and on top of an existing putter by clamping a clubhead between the face of the device and a set screw mounted on the underside of the device. The face of the device becomes the new striking surface, and provides improved tactile feedback and control of the golf ball. The top of the device provides alignment aids and also moves the center of gravity back away from the face and upwards from the sole of the existing putter. The threaded end near the back end of the device is used to house various weights or attachments which alter the overall weight, swing weight, and position of the center of gravity of the existing golf putter.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of Ser. No. 12/346,256, filed Dec. 30, 2008, now U.S. Pat. No. 8,621,708, issued Jan. 7, 2014, which is a divisional application of Ser. No. 11/276,167, filed Feb. 16, 2006, now U.S. Pat. No. 7,784,148, which claims the benefit of U.S. Provisional Patent Application No. 60/593,829, filed Feb. 17, 2005, and U.S. Provisional Patent Application No. 60/743,153, filed Jan. 20, 2006, all of which are incorporated herein by reference in their entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a surface cleaning apparatus that fluid cleaning system to deliver heated cleaning fluid to a surface to be cleaned. In one of its aspects, the invention relates to a surface cleaning apparatus that has an inline heater to heat cleaning fluid.
2. Description of the Related Art
Extractors are well-known devices for deep cleaning carpets and other fabric surfaces, such as upholstery. Most carpet extractors comprise a fluid delivery system and a fluid recovery system. The fluid delivery system typically includes one or more fluid supply tanks for storing a supply of cleaning fluid, a fluid distributor for applying the cleaning fluid to the surface to be cleaned, and a fluid supply conduit for delivering the cleaning fluid from the fluid supply tank to the fluid distributor. The fluid recovery system usually comprises a recovery tank, a nozzle adjacent the surface to be cleaned and in fluid communication with the recovery tank through a working air conduit, and a source of suction in fluid communication with the working air conduit to draw the cleaning fluid from the surface to be cleaned and through the nozzle and the working air conduit to the recovery tank. An example of an extractor is disclosed in commonly assigned U.S. Pat. No. 6,131,237 to Kasper et al., which is incorporated herein by reference in its entirety. The Kasper et al. '237 includes an aluminum body that includes a cover made of aluminum and further includes a fluid inlet fitting and a fluid outlet fitting connected to the metal body for circulating fluid through the metal body. Corrosion may be a problem resulting from casting the fluid inlet and fluid outlet fittings into the metal heater block. This problem might be overcome the use screw-in fittings with an O-ring rather than casting the fittings into the block. This solution may reduce the corrosion problem but may also add significant cost in that the block is required to be tapped and a hand assembly is required for threading the fittings into the tapped holes. Further, the metal cover may have to be Teflon coated to avoid corrosion problems.
The U.S. Patent Application Publication No. 2004/0197095 to Thweatt, Jr. discloses a heater for fluids including a housing made of non-metallic material and having an internal cavity and an inlet and an outlet in fluid communication with the internal cavity. The heater housing is made of a polymeric material. A heating element is suspended within the cavity for heating fluid flowing therethrough. Further, the heating element comprises a U-shaped portion and electrical connectors at opposite ends of the heating element which extend through the housing. Thweatt, Jr. '095 has fluid inlet and outlet fittings mounted to the heating element in an end wall of the plastic housing. The heating element may melt the walls of the plastic housing when the housing is dry, regardless of the existence of a thermal cutoff control.
SUMMARY OF THE INVENTION
A surface cleaning apparatus according to the invention comprises a housing, a fluid delivery system mounted to the housing and including a fluid supply chamber for holding a supply of cleaning fluid, a fluid dispenser for applying cleaning fluid from the fluid supply chamber to the surface to be cleaned, and a fluid supply conduit between the fluid supply chamber and the fluid dispenser. The apparatus further comprises a fluid recovery system mounted to the housing and including a suction nozzle and a vacuum source in fluid communication with the suction nozzle to draw dispensed fluid from the surface to be cleaned through the suction nozzle.
According to one embodiment of the invention, the apparatus further comprises an in-line fluid heater comprising a metal body with an embedded heating element and a polymeric cover with a fluid inlet fitting and a fluid outlet fitting connected in-line with the fluid supply conduit.
In another embodiment of the invention, the fluid inlet and outlet fittings of the heater are integrally molded with the cover.
In yet another embodiment of the invention, the metal body of the heater forms a fluid channel having an open upper end, and the cover closes the open upper end of the fluid channel to form a closed fluid channel in the fluid heater.
According to yet another embodiment of the invention, the heater cover is secured to the body of the heater with mechanical fasteners and a gasket located between the cover and the body.
BRIEF DESCRIPTION OF THE DRAWINGS
In the drawings:
FIG. 1 is a rear, left perspective view of an extractor according to the invention with a handle assembly pivotally mounted to a foot assembly.
FIG. 2 is a schematic view of a fluid delivery system for the extractor of FIG. 1 .
FIG. 3 is a top view of a heater for use with the fluid delivery system of FIG. 2 .
FIG. 4 is a sectional view taken along line 4 - 4 of FIG. 3 .
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings and particularly to FIG. 1 , an upright extractor 10 according to the invention comprises a housing having a foot assembly 12 for movement across a surface to be cleaned and a handle assembly 14 pivotally mounted to a rearward portion of the foot assembly 12 for directing the foot assembly 12 across the surface to be cleaned. The extractor 10 includes a fluid delivery system for storing cleaning fluid and delivering the cleaning fluid to the surface to be cleaned and a fluid recovery system for removing the spent cleaning fluid and dirt from the surface to be cleaned and storing the spent cleaning fluid and dirt. The components of the fluid delivery system and the fluid recovery system are supported by at least one of the foot assembly 12 and the handle assembly 14 . Details of the extractor 10 are more fully described in parent U.S. Patent Application Publication No. 2009/0101187, filed Dec. 30, 2008, entitled “Surface Cleaning Apparatus with Cleaning Fluid Supply”, which is incorporated herein by reference in its entirety.
The foot assembly 12 comprises a base assembly 20 that supports a recovery tank assembly 22 at a forward portion thereof and a solution supply tank assembly 24 at a rearward portion thereof. Further, a nozzle assembly 340 is removably mounted to a forward portion of the base assembly 20 .
Referring to FIGS. 1 and 2 , the extractor 10 comprises the fluid recovery system for removing the spent cleaning fluid and dirt from the surface to be cleaned and storing the spent cleaning fluid and dirt. The nozzle assembly 340 forms a portion of the fluid flow path, the opening of which is positioned adjacent a surface to be cleaned. When the nozzle assembly 340 and the recovery tank assembly 22 are mounted to the base assembly 20 , a continuous working air path is formed through the nozzle assembly 340 and the recovery tank assembly 22 . A vacuum is drawn on the recovery tank assembly 22 and nozzle assembly 340 by a motor and fan assembly 228 to draw spend cleaning fluid from the surface to be cleaned.
The solution supply tank assembly 24 is removably mounted to the base assembly 20 . The solution supply tank assembly 24 comprises a solution supply tank housing 150 that defines a solution supply chamber (not shown). The solution supply tank housing has outlet 156 in a bottom wall thereof. The outlet 156 receives a valve mechanism 158 for controlling flow of fluid from the solution supply chamber 152 . Spray tips 218 are in fluid communication with solution supply chamber 152 so that the fluid can be supplied from the spray tips 218 to the surface to be cleaned.
As mentioned above, the extractor 10 comprises the fluid delivery system for storing the cleaning fluid and delivering the cleaning fluid to the surface to be cleaned. For visual clarity, the various electrical and fluid connections within the fluid delivery system are not shown in the drawings described above but are depicted schematically in FIG. 2 . Referring now to FIG. 2 , the fluid delivery system comprises a bladder 44 for storing a first cleaning fluid and the solution supply tank housing 150 of the solution supply tank assembly 24 for storing a second cleaning fluid. The first and second cleaning fluids are dispensed from the bladder 44 and the solution supply tank housing 150 through respective valve mechanisms 48 , 158 , which are received by respective valve seats (not shown) when the recovery tank assembly 22 and the solution supply tank assembly 24 , respectively, are mounted to the base assembly 20 . The first cleaning fluid flows from the bladder 44 and through a heater 680 , which heats the first cleaning fluid when the heater 680 is activated through a heater switch 388 , to a mixing manifold 510 . The mixing manifold 510 forms a conduit for the first cleaning fluid between a first fluid inlet 510 A and an outlet 510 B and also includes two second cleaning fluid inlets 510 C, 510 D. The second cleaning fluid inlets 510 C, 510 D fluidly communicate with the conduit for the first cleaning fluid in a mixing chamber 510 E. The heater 680 can heat fluids and is preferably an in-line heater. Exemplary valve mechanisms and heaters are disclosed in U.S. Pat. No. 6,131,237 and U.S. patent application Ser. No. 60/521,693, which are incorporated herein by reference in their entirety.
In operation, when a user depresses a fluid trigger 460 on the handle assembly 14 , a trigger switch 462 opens a spray tip valve 224 to deliver cleaning fluid to the spray tips 218 for dispensation onto the surface to be cleaned.
The heater 680 for heating the cleaning fluid is illustrated in FIGS. 3 and 4 . The heater 680 is similar to the heater disclosed in the aforementioned and incorporated U.S. Pat. No. 6,131,237 in that the heater 680 comprises a metallic body 682 , such as an aluminum body, that forms a serpentine fluid channel 684 with an open upper end and houses a heating element 686 . The heater 680 further comprises a polymeric cover 688 mounted to the body 682 by mechanical fasteners 690 , such as screws, with a gasket 692 therebetween. The cover 688 comprises a fluid inlet port 694 and a fluid outlet port 696 , which are preferably integrally molded with the cover 688 . When the cover 688 is mounted to the body 682 , the cover 688 closes the open upper end of the fluid channel 684 , and the fluid inlet port 694 and the fluid outlet port 696 provide an inlet and an outlet, respectively, to the fluid channel 684 . During operation, the cleaning fluid flows through the fluid inlet port 694 into the fluid channel 684 and exits the fluid channel 684 through the fluid outlet port 696 . As the cleaning fluid flows through the fluid channel 684 , heat from the heating element 686 conducts through the body 682 and to the cleaning fluid to thereby heat the cleaning fluid.
The hybrid heater 680 according to the invention uses a metal block (body 682 ) with an embedded heating element 686 for efficient heat transfer but eliminates a metal cover and integrally forms the inlet and outlet ports 694 , 696 with the plastic cover 688 . Thus, the invention avoids the corrosion problems of the prior art while maintaining the heat transfer properties of the prior art and eliminates expensive machining operations, hand assembly and Teflon coating of the cover. The metal body 682 with the embedded heating element 686 stores heat energy and gives a thermal sensor the time to react. Thus, the invention involves the combination of a plastic cover that mounts the inlet and outlet ports 694 , 696 , preferably by integral molding.
The various features of the extractor 10 described here are not limited for use in an upright extractor. Rather, the features can be employed for any suitable surface cleaning apparatus, including, but not limited to, hand-held extractors, canister extractors, upright and canister vacuum cleaners, shampooing machines, mops, bare floor cleaners, and the like.
While the invention has been specifically described in connection with certain specific embodiments thereof, it is to be understood that this is by way of illustration and not of limitation. Reasonable variation and modification are possible within the scope of the forgoing description and drawings without departing from the spirit of the invention which is defined in the appended claims.
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A surface cleaning apparatus comprises a fluid delivery system including a supply of cleaning fluid stored in a fluid supply chamber and a fluid recovery system for drawing dirty cleaning fluid using suction from the surface to be cleaned. The apparatus has an inline fluid heater having a metal body with an embedded heating element and a polymeric cover provided with a fluid inlet fitting and a fluid outlet fitting. The fluid inlet and fluid outlet fittings are preferably integrally molded with the polymeric cover.
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BACKGROUND
[0001] Almost all incontinence products sold today, including diapers, training pants, adult incontinence products, absorbent swimwear, and the like are manufactured to be disposed of after a single use. The absorbent articles typically contain a cover material, a liner, and an absorbent structure positioned between the cover material and the liner. The absorbent structure may include superabsorbent particles. Many absorbent articles are so efficient at absorbing liquids that it is sometimes difficult to ascertain whether or not the absorbent article has been insulted with a bodily fluid.
[0002] Accordingly, various types of electrical monitoring devices, such as moisture or wetness indicators, have been suggested for use in absorbent articles. The electrical monitoring devices may include alarm devices that are designed to assist parents or attendants in identifying a wet diaper condition shortly after the diaper has been soiled. The devices may produce a visual, an audible, or an electronic signal. These electrical monitoring devices have been powered by batteries, specifically small coin cell batteries. The power that is supplied by batteries dissipates over time requiring that the batteries be periodically replaced. A need therefore exists for an absorbent article having an electrical monitoring device that includes a source of electrical energy generated from ambient energy.
SUMMARY
[0003] In general, the present disclosure is directed to an absorbent article. For example, in one embodiment, the absorbent article includes an outer cover material, a liner, and an absorbent structure positioned between the outer cover material and the liner. Further, the absorbent article includes a monitoring system, where the monitoring system includes a current source that provides electrical energy from ambient energy.
[0004] Another version of the present invention includes an absorbent article having an outer cover material, a liner, and an absorbent structure positioned between the outer cover material and the liner. The absorbent article includes a monitoring system, where the monitoring system comprises a current source that provides electrical energy from ambient energy. The ambient energy being either a temperature gradient, motion, light, or vibration. The absorbent article also has an accumulator that accumulates an electric charge from the current source.
[0005] Finally, another version of the present invention includes an absorbent article having an outer cover material, a liner, and an absorbent structure positioned between the outer cover material and the liner. The absorbent article includes a monitoring system, wherein the monitoring system comprises a current source that provides electrical energy from ambient energy. The absorbent article also includes an accumulator that accumulates an electric charge from the current source. Further, the accumulator is a battery.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] FIG. 1 is a side perspective of an article shown in the form of a pair of training pants having a mechanical fastening system fastened on one side of the training pants and unfastened on the opposite side thereof;
[0007] FIG. 2 is a perspective view of the pants of FIG. 1 ;
[0008] FIG. 3 is a perspective view of the pants similar to FIG. 2 showing a housing of a monitoring system removed from the article;
[0009] FIG. 4 is a top plan view of the training pants of FIG. 1 with the pants in an unfastened, unfolded, and laid flat condition, showing the surface of the training pants that faces the wearer when worn, with portions cut away to show underlying features;
[0010] FIG. 5 is a cross-sectional view of the pants taken along the plane including line 5 - 5 of FIG. 4 ;
[0011] FIG. 6 is a schematic illustration of the pants and one embodiment of a monitoring system;
[0012] FIG. 7 is a block diagram for one embodiment illustrating an order of operation for components/devices, including a measuring device for measuring an electrical property of the pants and an analog-to-digital converter for converting an analog output from a measuring device into digital values to be read by a microprocessor.
[0013] Corresponding reference characters indicate corresponding parts throughout the drawings.
DETAILED DESCRIPTION
[0014] Referring now to the drawings and in particular to FIG. 1 , an absorbent article is representatively illustrated therein in the form of children's toilet training pants and is indicated in its entirety by the reference numeral 20 . The absorbent article 20 may or may not be disposable, which refers to articles that are intended to be discarded after a limited period of use instead of being laundered or otherwise conditioned for reuse. It is understood that the present invention is suitable for use with various other absorbent articles intended for personal wear, including but not limited to diapers, feminine hygiene products, incontinence products, medical garments, surgical pads and bandages, other personal care or health care garments, and the like without departing from the scope of the present invention.
[0015] By way of illustration only, various materials and methods for constructing training pants such as the pants 20 , are disclosed in PCT Patent Application WO 00/37009 published Jun. 29, 2000, by A. Fletcher et al; U.S. Pat. No. 4,940,464 issued Jul. 10, 1990, to Van Gompel et al.; U.S. Pat. No. 5,766,389 issued Jun. 16, 1998, to Brandon et al., and U.S. Pat. No. 6,645,190 issued Nov. 11, 2003, to Olson et al. which are incorporated herein by reference.
[0016] The pair of training pants 20 is illustrated in FIG. 1 in a partially fastened condition. The pants 20 define a longitudinal direction 48 of the pants and a lateral direction 49 thereof perpendicular to the longitudinal direction as shown in FIG. 4 . The pants 20 further define a pair of longitudinal end regions, otherwise referred to herein as a front waist region, generally indicated at 22 , and a back waist region, generally indicated at 24 , and a center region, otherwise referred to herein as a crotch region, generally indicated at 26 , extending longitudinally between and interconnecting the front and back waist regions 22 , 24 . The front and back waist regions 22 , 24 comprise those portions of the pants 20 , which when worn, wholly or partially cover or encircle the waist or mid-lower torso of the wearer. The crotch region 26 generally is that portion of the pants 20 which, when worn, is positioned between the legs of the wearer and covers the lower torso and crotch of the wearer. The pants 20 also define an inner surface 28 that faces toward the wearer when the pants are being worn, and an outer surface 30 opposite the inner surface. With additional reference to FIG. 4 , the pair of training pants 20 has a pair of laterally opposite side edges 36 and a pair of longitudinally opposite waist edges (broadly, longitudinal ends), respectively designated front waist edge 38 and back waist edge 39 .
[0017] In the embodiment of FIGS. 1-4 , the training pants 20 comprise a generally rectangular central absorbent assembly, generally indicated at 32 , and side panels 34 A, 34 B formed separately from and secured to the central absorbent assembly. The side panels 34 A, 34 B are permanently bonded along seams to the central absorbent assembly 32 in the respective front and back waist regions 22 and 24 of the pants 20 . More particularly, the front side panels 34 A can be permanently bonded to and extend transversely outward beyond side margins 47 of the absorbent assembly 32 at the front waist region 22 , and the back side panels 34 B can be permanently bonded to and extend transversely outward beyond the side margins of the absorbent assembly at the back waist region 24 . The side panels 34 A and 34 B may be bonded to the absorbent assembly 32 using attachment means known to those skilled in the art such as adhesive, thermal or ultrasonic bonding.
[0018] The front and back side panels 34 A and 34 B, upon wearing of the pants 20 , thus comprise the portions of the training pants 20 which are positioned on the hips of the wearer. The front and back side panels 34 A and 34 B can be permanently bonded together to form the three-dimensional configuration of the pants 20 , or be releasably connected with one another such as by a fastening system 59 of the illustrated aspects. As is known in the art, the side panels 34 A, 34 B may comprise elastic material or stretchable but inelastic materials.
[0019] The absorbent assembly 32 is illustrated in FIGS. 1-3 as having a rectangular shape. However, it is contemplated that the absorbent assembly 32 may have other shapes (e.g., hourglass, T-shaped, I-shaped, and the like) without departing from the scope of this invention. It is also understood that the side panels 34 A, 34 B may instead be formed integrally with the absorbent assembly 32 without departing from the scope of this invention.
[0020] As shown best in FIGS. 4 and 5 , the absorbent assembly 32 comprises an outer cover 40 and a bodyside liner 42 attached to the outer cover 40 in a superposed (opposed) relation therewith by adhesives, ultrasonic bonds, thermal bonds, pressure bonds, or other conventional techniques. The liner 42 is suitably joined to the outer cover 40 along at least a portion of the longitudinal ends of the pants 20 . In addition, the liner 42 is suitably joined to the outer cover 40 along at least a portion of the lateral side edges of the pant 20 . The liner 42 is suitably adapted, i.e., positioned relative to the other components of the pants 20 , for a contiguous relationship with the wearer's skin during wear of the pants. The absorbent assembly 32 also comprises an absorbent structure 44 disposed between the outer cover 40 and the bodyside liner 42 for absorbing liquid body exudates released by the wearer and a surge management layer 45 disposed between the absorbent structure and the bodyside liner. A pair of containment flaps 46 is secured to the bodyside liner 42 for inhibiting the lateral flow of body exudates.
[0021] With the training pants 20 in the fastened position as partially illustrated in FIG. 1 , the front and back waist regions are connected together by the fastening system 48 to define the three-dimensional pants configuration having a waist opening 50 and a pair of leg openings 52 . The front and back waist edges 38 and 39 (e.g., longitudinal ends) of the training pants 20 are configured to encircle the waist of the wearer to define the waist opening 50 ( FIG. 1 ) of the pants.
[0022] As illustrated in FIG. 4 , a flap elastic member 53 can be operatively joined with each containment flap 46 in any suitable manner as is well known in the art. Suitable constructions and arrangements for the containment flaps 46 are generally well known to those skilled in the art and are described in U.S. Pat. No. 4,704,116 issued Nov. 3, 1987, to Enloe, which is incorporated herein by reference.
[0023] To further enhance containment and/or absorption of body exudates, the training pants 20 may comprise a front waist elastic member 54 ( FIG. 1 ), a rear waist elastic member 56 , and leg elastic members 58 ( FIGS. 2-4 ), as are known to those skilled in the art. The flap elastic members 53 , the waist elastic members 54 and 56 , and the leg elastic members 58 can be formed of any suitable elastic material that is well known to those skilled in the art.
[0024] The fastening system 80 of the illustrated embodiment comprises laterally opposite first fastening components 60 adapted for refastenable engagement to corresponding laterally opposite second fastening components 62 . In one embodiment, a front or outer surface of each of the fastening components 60 , 62 comprise a plurality of engaging elements. The engaging elements of the first fastening components 60 are adapted to repeatedly engage and disengage corresponding engaging elements of the second fastening components 62 to releasably secure the pants 20 in its three-dimensional configuration. The fastening components 60 , 62 can comprise any refastenable fasteners suitable for absorbent articles such as adhesive fasteners, cohesive fasteners, mechanical fasteners, or the like. Suitable fastening systems are also disclosed in the previously incorporated PCT Patent Application WO 00/37009 published Jun. 29, 2000, by A. Fletcher et al. and the previously incorporated U.S. Pat. No. 6,645,190 issued Nov. 11, 2003, to Olson et al.
[0025] The outer cover 40 suitably comprises a material that is substantially liquid impermeable. The outer cover 40 may comprise a single layer of liquid impermeable material, or more suitably comprise a multi-layered laminate structure in which at least one of the layers is liquid impermeable. While it is not a necessity for the outer layer to be liquid permeable, it is suitable that it provides a relatively cloth-like texture to the wearer. Alternatively, the outer cover 40 may comprise a woven or non-woven fibrous web layer that has been totally or partially constructed or treated to impart the desired levels of liquid impermeability to selected regions that are adjacent or proximate to the absorbent structure. The outer cover 40 may also be stretchable, and in some embodiments it may be elastomeric. Reference is made to U.S. Pat. No. 5,883,028, issued to Morman et al., U.S. Pat. No. 5,116,662 issued to Morman and U.S. Pat. No. 5,114,781 issued to Morman, all of which are hereby incorporated herein by reference, for additional information regarding suitable outer cover materials.
[0026] The bodyside liner 42 is suitably compliant, soft-feeling, and non-irritating to the wearer's skin. The bodyside liner 42 is also sufficiently liquid permeable to permit liquid body exudates to readily penetrate through its thickness to the absorbent structure 44 . The bodyside liner 42 may also be stretchable, and in some embodiments it may be elastomeric. Reference is made to U.S. patent application Ser. No. 09/563,417 filed on May 3, 2000, by Roessler et al., U.S. patent application Ser. No. 09/698,512 filed on Oct. 27, 2000, by Vukos et al., both of which are incorporated by reference herein, for additional information regarding bodyside liner material.
[0027] The absorbent structure 44 is disposed between the outer cover 40 and the bodyside liner 42 , which can be joined together by any suitable means such as adhesives, ultrasonic bonds, thermal bonds, or the like. While the illustrated absorbent structure 44 is shown and described herein as extending from the crotch region 26 into both the front and back waist regions 22 and 24 , it is contemplated that the absorbent structure may extend from the crotch region into only the front waist region, or only the back waist region, without departing from the scope of this invention.
[0028] The absorbent structure 44 is suitably compressible, conformable, non-irritating to a wearer's skin, and capable of absorbing and retaining liquids and certain body wastes. For example, the absorbent structure 44 may comprise cellulosic fibers (e.g., wood pulp fibers), other natural fibers, synthetic fibers, woven or nonwoven sheets, scrim netting or other stabilizing structures, superabsorbent material, binder materials, surfactants, selected hydrophobic materials, pigments, lotions, odor control agents, or the like, as well as combinations thereof.
[0029] The materials may be formed into an absorbent web structure by employing various conventional methods and techniques known in the art. For example, the absorbent structure 44 may be formed by a dry-forming technique, an air forming technique, a wet-forming technique, a foam-forming technique, or the like, as well as combinations thereof. Methods and apparatus for carrying out such techniques are well known in the art. The absorbent structure 44 may alternatively comprise a coform material such as the material disclosed in U.S. Pat. No. 4,100,324 to Anderson, et al.; U.S. Pat. No. 5,284,703 to Everhart, et al.; and U.S. Pat. No. 5,350,624 to Georger, et al.; which are incorporated herein by reference.
[0030] Superabsorbent material is suitably present in the absorbent structure 44 in an amount of from about 0 to about 90 weight percent based on total weight of the absorbent structure. The absorbent structure 44 may suitably have a density within the range of about 0.10 to about 0.35 grams per cubic centimeter. Superabsorbent materials are well known in the art and can be selected from natural, synthetic, and modified natural polymers and materials.
[0031] In one embodiment, the absorbent structure 44 may be stretchable so as not to inhibit the stretchability of other components to which the absorbent structure may be adhered, such as the outer cover 40 and bodyside liner 42 . For example, the absorbent structure may comprise materials disclosed in U.S. Pat. Nos. 5,964,743; 5,645,542; 6,231,557; 6,362,389; and international patent application WO 03/051254, the disclosure of each of which is incorporated by reference herein.
[0032] The surge management layer 45 may be attached to various components of the article 20 such as the absorbent structure 44 and/or the bodyside liner 42 by methods known in the art, such as by adhesive, ultrasonic, or thermal bonding. The surge management layer 45 helps to decelerate and diffuse surges or gushes of liquid that may be rapidly introduced into the absorbent structure 44 of the article 20 . Desirably, the surge management layer 45 can rapidly accept and temporarily hold the liquid prior to releasing the liquid into the storage or retention portions of the absorbent structure 44 . Examples of suitable surge management layers 45 are described in U.S. Pat. No. 5,486,166 and U.S. Pat. No. 5,490,846. Other suitable surge management materials are described in U.S. Pat. No. 5,820,973. The entire disclosures of these patents are incorporated by reference herein.
[0033] Optionally, a substantially liquid permeable wrapsheet (not shown) may surround the absorbent structure 44 to help maintain the integrity of the absorbent structure 44 .
[0034] The training pants 20 include a monitoring system that includes one or more sensors. The monitoring system may include sensors to indicate the presence of moisture or a bowel movement. The monitoring system may include a biosensor. The biosensor may be activated when contacted with an analyte contained in a body fluid. The analyte may be, for instance, a protein, a glycoprotein, an antibody, an antigen, hemoglobin, an enzyme, a metal salt, a hormone, or the like.
[0035] Healthcare products and incontinence products in care-giving institutions may include a monitoring system adapted to monitor humidity, temperature or a host of bio-indicators. In incontinence articles, for example, biosensors for a variety of disease conditions (e.g., cancer, diabetes, etc.) may be present and associated with respective warning indicators that are activated when a positive reading for a target analyte occurs. In one particular embodiment, the biosensor may be configured to sense a particular protein that would indicate a kidney problem. The monitoring system may also monitor the hydration level with a sensor quantifying the ionic strength of urine. Alternatively, the system may monitor sugar in urine or indicators for yeast in feminine care products.
[0036] Although the monitoring system may take on other configurations, this representative configuration of the system monitors an electrical characteristic of the pants and determines whether the child has urinated in the pants using such electrical characteristic. After detection of urine, the system may inform a caregiver and/or a child of the presence of the urine by generating an insult alarm. The alarm may be, for example, either an auditory signal, such as a song, or a tactile signal, such as temperature change, or a visual signal, such as a blinking light. It is understood that the system may comprise a device for sending a wireless signal to a remote auditory, visual, tactile or other sensory alarm.
[0037] In one particularly suitable embodiment, shown best in FIGS. 2-4 , one example of the monitoring system is generally indicated by reference numeral 70 . The monitoring system 70 includes a sensor for detecting the electrical property (e.g., resistance Ω) of the article. The sensor includes a pair of spaced-apart generally parallel conductors C 1 , C 2 disposed within the pants 20 that define a monitoring area 74 of the pants disposed between the conductors. The conductors C 1 , C 2 may be constructed of any material that is generally electrically conductive. For example, the conductors may be constructed of metal strips (e.g., aluminum strips), metal films, coated films, conductive polymers, conductive inks, or conductive threads. Other conductors are within the scope of this invention. The conductors C 1 , C 2 extend longitudinally from the front waist region 22 , through the crotch region 26 , to the back waist region 24 of the pants 20 . As shown best in FIG. 5 , the conductors C 1 , C 2 are disposed within the absorbent assembly 32 between the absorbent structure 44 and the surge management layer 45 , although the conductors may be disposed at other locations without departing from the scope of this invention.
[0038] Current i from a current source B (illustrated schematically in FIG. 6 ) runs through the conductors C 1 , C 2 of the sensor. The current source B may be a single current source, a plurality of current sources, or a combination of current sources and current accumulators as described below. The current source B may be a direct current source or an alternating current source. The current source B provides electrical energy for the monitoring system from ambient energy as described below. In the illustrated embodiment, the conductors C 1 , C 2 are electrically connected to the current source by way of electrically conductive snap fasteners 79 . Other ways of electrically connecting the conductors to the current source are within the scope of this invention. As illustrated in FIG. 3 , each corresponding end of each conductor C 1 , C 2 is connected to a first snap fastener member 79 A located in the front waist region 22 of the pants 20 . Alternatively, the first snap fastener member may be located in the back waist region 24 , or other locations on the pants 20 . A housing 82 that houses the current source B has corresponding second snap fastener elements 79 B for engaging the first snap fasteners 79 A and securing the housing to the pants 20 . In addition to the current source B, the housing 82 of the present embodiment also houses the remaining components of the monitoring system 70 that will be described hereinafter, although it is contemplated that the housing may include only some or none of the remaining components. In the illustrated embodiment the housing 82 is releasably secured to the pants 20 by way of the snap fasteners 79 , although it is understood that the housing may be permanently secured to the pants without departing from the scope of this invention.
[0039] A measuring device 85 ( FIG. 6 ) of the sensor measures an electrical property of the monitoring area 74 of the pants 20 . In one embodiment, the resistance R of the monitoring area 74 of the pants 20 is measured. Because the conductors C 1 , C 2 are spaced apart, current from the current source B must pass through the monitoring area 74 to complete the circuit. As illustrated schematically in FIG. 6 , the monitoring area 74 acts essentially as a resistor, as indicated by reference character R. When the monitoring area 74 is dry (e.g., before the presence of an insult), the resistance of the monitoring area is relatively high, for example, some resistance above 200 kΩ. When the monitoring area 74 is wetted, its resistance drops, to some resistance less than 200 kΩ because of the electrically conductive nature of urine.
[0040] In another embodiment, the conductance of the monitoring area 74 of the pants 20 is measured. As stated above, urine is electrically conductive and the article 20 generally is not electrically conductive. Therefore, when the monitoring area 74 of the pants 20 is wetted, its conductance is greater than when it is dry. Other electrical properties of the pants 20 , including impedance, may be measured without departing from the scope of this invention.
[0041] The measuring device 85 produces an analog output signal ( FIG. 6 ) indicative of the electrical property of the monitoring area 74 of the pants 20 . For example, the measuring device 85 can measure a resistance drop across the monitoring area 74 , and produce an analog output signal corresponding to the resultant voltage drop. The output voltage signal can be used to determine other electrical properties, such as resistance or current, by performing suitable calculations known in the art or by using a reference table. For example, as is well known in the art, the voltage drop is indicative of the resistance of the pants when the current is constant. Thus, as explained below in further detail, the resistance of the pants 20 may be determined using the analog output signal of the measuring device 85 .
[0042] In one embodiment, a percent difference test is conducted on the measured resistance of the pants 20 to determine the presence (or lack thereof) of an insult in the pants as the pants are being worn by the user. In this embodiment, a proportional difference (e.g., a percent difference) in the measured electrical property of the monitoring area of the pants over time is determined, and this proportional difference is compared with a difference threshold value to determine if an insult is present in the pants.
[0043] In one example of this embodiment, illustrated in FIG. 7 , an analog-to-digital converter 89 receives the analog output signal from the measuring device 85 and converts the signal into a digital output signal. A microprocessor 93 receives the digital output signal, which is representative of the magnitude of the electrical property (e.g., resistance) of the pants 20 , and analyzes it to determine the presence of an insult. If the microprocessor 93 detects the presence of an insult, then it may activate the insult alarm 95 . The analog-to-digital converter 89 is a conventional device for converting analog signals into digital signals that can be read by a microprocessor. The analog-to-digital converter 89 of the present embodiment may be a separate device or it may be a component of the microprocessor 93 . For illustrative purposes, the electrical property will hereinafter be referred to as resistance although, as noted above, it may be any variable property of the garment which reflects wetness.
[0044] The sole current source B in traditional monitoring systems in absorbent articles has been batteries. The current that is supplied by batteries dissipates over time. As such, the traditional monitoring systems have had the disadvantage that either the batteries required changing, or in systems with batteries that couldn't be changed, the monitoring system had a limited life.
[0045] The monitoring systems of the present invention include a current source that provides electrical energy from ambient energy. Ambient energy is any energy that is generally present in the user's environment and is not directed to power electrical devices. Examples of ambient energy include motion, light, a temperature gradient, and vibration. The ambient energy may come from the user of the absorbent article. For example, the ambient energy may be motion from the user or a temperature gradient between the skin of the user and room temperature. The ambient energy may come from the environment that the user is in, for example the sun if the user is outdoors or electric lighting if the user is indoors.
[0046] A current source that provides electrical energy from ambient energy provides several benefits over a current source that dissipates over time. These benefits may include longer shelf life and longer usable life. These benefits are useful in the context of monitoring systems incorporated into absorbent articles.
[0047] A long shelf life may be particularly useful for absorbent articles used for toilet training. A caregiver may purchase a package of diapers or training pants having a monitoring system for the purpose of toilet training. If the user of the articles becomes toilet trained before the package of articles are depleted, there will be leftover articles. These articles may be disposed of, given to others, or perhaps saved for use on another child in the family. In this last instance, the articles may sit unused for months or, more likely, years. An absorbent article having a monitoring system including a current source that provides electrical energy from ambient energy provides a caregiver with confidence that the monitoring system will be useful for immediate use with a first child and for use in the future with a second child.
[0048] A long useable life is also useful in absorbent articles used for toilet training. The current source of the monitoring system may be included in a durable portion of the system that is designed to be moved from a first absorbent article to a second absorbent article. Some users in training may use this durable portion including the current source for many months, and perhaps more than a year. The life may be even longer if the durable portion of the system is then used by a subsequent user. A current source that provides electrical energy from ambient energy may theoretically power a monitoring system indefinitely, providing a consistent response. This consistent response may be critical in effective toilet training. A monitoring system that relies solely on battery power may provide an inconsistent response when the battery is depleted.
[0049] Many absorbent articles are designed to be fit near or around the waist and legs of a user. In addition, these articles may be designed to be as discrete as possible. A monitoring system incorporated into these articles would also be located near or around the waist and legs, and also be designed to be as discrete as possible. A monitoring system that provides electrical energy from ambient energy may be designed to provide additional functions beyond providing a current source. For example, in the case of electrostrictive polymers, the current source may also provide one or more elastic components to the absorbent article, for example waist elastic members 54 , 56 , leg elastic members 58 , or flap elastic members 53 . This multi-functional aspect may provide for a smaller, more discrete monitoring system.
[0050] As stated above, the ambient energy may be a temperature gradient. In this case, a thermoelectric generator takes advantage of a thermal gradient to generate a current according to the Seebeck effect. The thermoelectric generator may comprise a bottom plate, a top plate, and an array of foil segments. The array of foil segments is interposed between the bottom plate and the top plate in a side-by-side arrangement. Each of the foil segments is perpendicularly disposed between and in thermal contact with the bottom and top plates. A series of alternating n-type and p-type thermoelectric legs is disposed on a substrate of each one of the foil segments. The thermoelectric legs are generally fabricated from a bismuth telluride-type thermoelectric material, although any suitable material may be used. The top plate is disposed in spaced relation above the bottom plate.
[0051] The bottom and top plates may have a generally orthogonal configuration and may be fabricated from any rigid material such as ceramic material. The bottom plate and top plate are configured to provide thermal contact between a heat sink and a heat source such that a temperature gradient may be developed across the alternating n-type and p-type thermoelectric legs. The bottom plate may be thermally connected to the air surrounding a user and the top plate may be thermally connected to the skin of a user.
[0052] Each one of the foil segments may have a front substrate surface and a back substrate surface opposing the front substrate surface. The foil segments are arranged such that the back substrate surface of a foil segment faces the front substrate surface of an adjacent foil segment. The spaced, alternating n-type and p-type thermoelectric legs may be disposed in parallel arrangement to each other on the front substrate surface. Each of the n-type and p-type thermoelectric legs may be formed of a thermoelectric material generally having a thickness in the range of from about 5 microns (μm) to about 100 μm, with a preferable thickness of about 7 μm. The front substrate surface may have a surface roughness that is smoother than that of the back substrate surface in order to enhance the repeatability of forming the n-type and p-type thermoelectric legs on the front substrate surface.
[0053] A p-type and n-type thermoelectric leg pair makes up a thermocouple of the thermoelectric generator. The width of the thermoelectric legs may be in the range of from about 10 μm to about 100 μm. The length of the thermoelectric legs may be in the range of from about 100 μm to about 500 μm. A preferred length of the n-type and p-type thermoelectric legs is about 500 μm. A preferred width of the n-type thermoelectric leg is about 60 μm, while a preferred width of the p-type thermoelectric leg is about 40 μm. The geometry of the respective n-type and p-type thermoelectric legs may be adjusted to a certain extent depending on differences in the electrical conductivities of each n-type and p-type thermoelectric leg.
[0054] Alternatively, as stated above, the ambient energy source may be motion or vibration. In this case, a piezo-electric generator or electrostrictive polymer may take advantage of the motion or vibration to produce a current.
[0055] In the case of vibration, a piezo-electric generator may take advantage of a vibration to produce a current. In a piezo-electric generator, a pair of electrodes are provided on a piezo-electric plate. The piezo-electric plate moves when vibrated such that the piezo-electric plate is expanded or contracted during vibration. This expansion and contraction generates an AC voltage. Also a combination of vibration plates, orthogonal to one another, may be used so that the vibration can be divided two-dimensionally or three-dimensionally. This vibration may be caused by large movements of the user, for example walking or crawling, or by smaller movements of the wearer, for example breathing.
[0056] In the case of motion, a piezo-electric generator or an electrostrictive polymer may take advantage of the motion to produce a current. Electrostrictive (or synonymously, electroactive) polymers have been known to be used as low-mass actuators (artificial muscles). In one such artificial muscle application, a voltage is applied across the electrostrictive polymer via electrodes, causing the polymer to bend, stretch, or otherwise move or deform. The electrostrictive polymers can be dimensionally altered to a much greater extent than piezoelectric materials. This property of electrostrictive polymers may be used in reverse to harvest or generate electrical power from the general movement of objects such as from a human walking or crawling. As stated above, the electrostrictive polymers may comprise elastic elements of the absorbent article.
[0057] The polymer may be arranged in a variety of ways. Some candidate polymers for this application are, for example, polyacrylic acid, often referred to as PAA, and polyvinyl chloride (PVC). In addition, poly (3,3′-phthalidylidene-4,4′-biphenylylene), abbreviated PPB, is also a candidate electrostrictive polymer.
[0058] A promising polymer-electrode configuration for power generation, for example, is essentially a sandwich structure where polymer material and electrodes are interleaved. This combination of polymers between conductive sheets may be called ion-exchange polymer-metal composites or IPMCs for short.
[0059] The electrodes may be wired (hooked-up) in a “series” configuration. In this configuration, adjacent positive electrodes are attached to nearest neighbor negative electrodes. This series hook-up configuration for the interleaved electrodes permits the voltages generated across each polymer to be added, so that a relatively high ultimate output voltage is generated by the system. Alternatively, a parallel hook-up may be provided. In yet another configuration, combinations of series and parallel hook-ups are possible.
[0060] As stated above, the ambient energy may be light. In this case, a solar cell may take advantage of the light to produce a current. Solar cells may be comprised of semiconductor materials, such as silicon. In solar cells, a thin semiconductor wafer is specially treated to form an electric field, positive on one side and negative on the other. When light energy strikes the solar cell, electrons are knocked loose from the atoms in the semiconductor material. If electrical conductors are attached to the positive and negative sides, forming an electrical circuit, the electrons can be captured in the form of an electric current.
[0061] A photovoltaic module is a number of solar cells electrically connected to each other and mounted in a support structure or frame. Modules are designed to supply electricity at a certain voltage, such as a common 12-volt system. The current produced is directly dependent on how much light strikes the module.
[0062] An absorbent article having a monitoring system including a current source that provides electrical energy from ambient energy may utilize a single source of ambient energy. For example, the source may be a temperature gradient only utilizing a thermoelectric generator. Alternatively a plurality of sources of ambient energy may be utilized, for example a temperature gradient utilizing a thermoelectric generator and light utilizing a solar cell. This second configuration may be useful in situations when a single source may not provide a steady supply of current. In these situations, the multiple supplies of current may be chosen dependent upon the specific absorbent article and current demands of the monitoring system.
[0063] An absorbent article having a monitoring system including a current source that provides electrical energy from ambient energy may also include an accumulator that accumulates an electric charge from the current source. As stated above, the current sources that provide electrical energy from ambient energy may not provide a steady supply of electrical energy, therefore, an accumulator may be incorporated into the monitoring system. During periods when an excess amount of electrical energy is provided by ambient energy, the accumulator may store the excess electrical energy. The accumulator may then release the electrical energy during periods when a shortage of electrical energy is provided by ambient energy.
[0064] The accumulator may be any device adapted to accumulate, store, and release an electrical charge. The accumulator may store the electrical charge in any form, for example chemically, electrically, or mechanically. Suitable devices include batteries, capacitors, flywheels, and the like. A single accumulator may be used; alternatively, a plurality of similar or dissimilar accumulators may be used.
[0065] An absorbent article having a monitoring system including a current source that provides electrical energy from ambient energy may also include a second current source that provides electrical energy from non-ambient energy. This second source may be a battery. The second source may be an antenna that harvests tuned electromagnetic radio frequencies such as used in RFID devices. The second source may be a pair of electrodes that create a galvanic couple upon the addition of a conductive fluid, for example the addition of urine.
[0066] When introducing elements of the present invention or the embodiments thereof, the articles “a”, “an”, “the”, and “said” are intended to mean that there are one or more of the elements. The terms “comprising”, “including”, and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.
[0067] As various changes could be made in the above constructions, products, and methods without departing from the scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
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Electrical monitoring devices may include alarm devices that are designed to assist parents or attendants in identifying a wet diaper condition shortly after the diaper has been soiled. The devices may produce a visual, an audible, or an electronic signal. These electrical monitoring devices have been powered by batteries, specifically small coin cell batteries. The power that is supplied by batteries dissipates over time requiring that the batteries be periodically replaced.
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FIELD OF THE INVENTION
[0001] The present invention concerns a titanium compressor wheel for use in an air boost device, capable of operating at high RPM with acceptable aerodynamic performance, yet capable of being produced economically by an investment casting process.
DESCRIPTION OF THE RELATED ART
[0002] Air boost devices (turbochargers, superchargers, electric compressors, etc.) are used to increase combustion air throughput and density, thereby increasing power and responsiveness of internal combustion engines. The design and function of turbochargers are described in detail in the prior art, for example, U.S. Pat. Nos. 4,705,463, 5,399,064, and 8,164,931, the disclosures of which are incorporated herein by reference.
[0003] The blades of a compressor wheel have a highly complex shape, for (a) drawing air in axially, (b) accelerating it centrifugally, and (c) discharging air radially outward at elevated pressure into the volute-shaped chamber of a compressor housing. In order to accomplish these three distinct functions with maximum efficiently and minimum turbulence, the blades can be said to have three separate regions.
[0004] First, the leading edge of the blade can be described as a sharp pitch helix, adapted for scooping air in and moving air axially. Considering only the leading edge of the blade, the cantilevered or outboard tip travels faster (MPS) than the part closest to the hub, and is generally provided with an even greater pitch angle than the part closest to the hub (see FIG. 1 ). Thus, the angle of attack of the leading edge of the blade undergoes a twist from lower pitch near the hub to a higher pitch at the outer tip of the leading edge. Further, the leading edge of the blade generally is bowed, and is not planar. Further yet, the leading edge of the blade generally has a “dip” near the hub and a “rise” or convexity along the outer third of the blade tip. These design features are all designed to enhance the function of drawing air in axially.
[0005] Next, in the second region of the blades, the blades are curved in a manner to change the direction of the airflow from axial to radial, and at the same time to rapidly spin the air centrifugally and accelerate the air to a high velocity, so that when diffused in a volute chamber after leaving the impeller the energy is recovered in the form of increased pressure. Air is trapped in airflow channels defined between the blades, as well as between the inner wall of the compressor wheel housing and the radially enlarged disc-like portion of the hub which defines a floor space, the housing-floor spacing narrowing in the direction of air flow.
[0006] Finally, in the third region, the blades terminate in a trailing edge, which is designed for propelling air radially out of the compressor wheel. The design of this blade trailing edge is generally complex, provided with (a) a pitch, (b) an angle offset from radial, and/or (e) a back taper or back sweep (which, together with the forward sweep at the leading edge, provides the blade with an overall “S” shape). Air expelled in this way has not only high flow, but also high pressure.
[0007] Recently, tighter regulation of engine exhaust emissions has led to an interest in even higher pressure ratio boosting devices. However, current compressor wheels are not capable of withstanding repeated exposure to higher pressure ratios (> 3 . 8 ). While aluminum is a material of choice for compressor wheels due to low weight and low cost, the temperature at the blade tips, and the stresses due to increased centrifugal forces at high RPM, exceed the capability of conventionally employed aluminum alloys. Refinements have been made to aluminum compressor wheels, but due to the inherent limited strength of aluminum, no further significant improvements can be expected. Accordingly, high pressure ratio boost devices have beer, found in practice to have short life, to be associated with high maintenance cost, and thus have too high a product life cost for widespread acceptance.
[0008] Titanium, known for high strength and low weight, might at first seem to be a suitable next generation material. Large titanium compressor wheels have in fact long been used in turbojet engines and jet engines from the B-52B/RB-52B to the F-22. However, titanium is one of the most difficult metals to work with, and currently the cost of production associated with titanium compressor wheels is so high as to limit wide spread employment of titanium.
[0009] There are presently no known cost-effective manufacturing techniques for manufacturing automobile or truck industry scale titanium compressor wheels. The automotive industry is driven by economics. While there is a need for a high performance compressor wheel, it must be capable of being manufactured at reasonable cost.
[0010] One example of a patent teaching casting of compressor wheels is U.S. Pat. No. 4,556,528 (Gersch et al) entitled “Method and Device for Casting of Fragile and Complex Shapes”. This patent illustrates the complex design of compressor wheels (as discussed in detail above), and the complex process involved in forming a resilient pattern for subsequent use in forming molds. More specifically, Gersch et al teach a process involving placing a solid positive resilient master pattern of an impeller into a suitable flask, pouring a flexible and resilient material, such as silastic or platinum rubber material, over the master pattern, curing, and withdrawing the solid master pattern of the impeller from the flexible material to form a flexible mold with a reverse or negative cavity of the master pattern. A flexible and resilient curable material is then poured into the cavity of the reverse mold. After the flexible and resilient material cures to form a positive flexible pattern of the impeller, it is removed from the flexible negative mold. The flexible positive pattern is then placed in an open top metal flask, and foundry plaster is poured into the flask. After the piaster has set up, the positive flexible pattern is removed from the plaster, leaving a negative plaster mold. A non-ferrous molten material (e.g., aluminum) is poured into the plaster mold, After the non-ferrous molten material solidifies and cools, the plaster is destroyed and removed to produce a positive non-ferrous reproduction of the original part.
[0011] While the Gersch et al process is effective for forming cast aluminum compressor wheels, it is limited to non-ferrous or lower temperature or minimally reactive casting materials and cannot be used for producing parts of high temperature casting materials such as ferrous metals and titanium. Titanium, being highly reactive, requires a ceramic shell.
[0012] U.S. Pat. No. 6,019,927 (Galliger) entitled “Method of Casting a Complex Metal Part” teaches a method for casting a titanium gas turbine impeller which, though different in shape from a compressor wheel, does have a complex geometry with walls or blades defining undercut spaces. A flexible and resilient positive pattern is made, and the pattern is dipped info a ceramic molding media capable of drying and hardening. The pattern is removed from the media to form a ceramic layer on the flexible pattern, and the layer is coated with sand and air-dried to form a ceramic layer. The dipping, sanding and drying operations are repeated several times to form a multi-layer ceramic shell. The flexible wall pattern is removed from the shell, by partially collapsing with suction if necessary, to form a first ceramic shell mold with a negative cavity defining the part. A second ceramic shell mold is formed on the first shell mold to define the back of the part and a pour-passage, and the combined shell molds are fired in a kiln. A high temperature casting material is poured into the shell molds, and after the casting material solidifies, the shell molds are removed by breaking.
[0013] It is apparent that the Galliger gas turbine flexible pattern is (a) collapsible and (b) is intended for manufacturing large-dimension gas turbine impellers for jet or turbojet engines. This technique is not suitable for mass-production of automobile scale compressor wheels with thin blades, using a non-collapsing pattern, Galliger does not teach a method which could be adapted to in the automotive industry.
[0014] In addition to the above “rubber pattern” technique for forming casting molds, there is a well-known process referred to as “investment casting” which can be used for making compressor wheels and which involves:
(1) making a wax pattern of a hub with cantilevered airfoils, (2) casting a refractory mass about the wax pattern, (3) removing the wax by solvent or thermal means, to form a casting mold, (4) pouring and solidifying the casting, and
(5) removing the mold materials.
[0020] There are however significant problems associated with the initial step of forming the compressor wheel wax pattern. Whenever a die is used to cast the wax pattern, the casting die must be opened to release the product. Herein, the several parts of the die (die inserts) must each be retracted, generally only in a straight (radial) line.
[0021] As discussed above, the blades of a compressor wheel have a complex shape. The complex geometry of the compressor wheel, with undercut recesses and/or back tapers created by the twist of the individual air foils with compound curves, not to mention dips and humps along the leading edge of the blade, impedes the withdrawal of die inserts.
[0022] In order to side-step these complexities, it has been known to fashion separate molds for each of the wax blades and for the wax hub. The separate wax blades and hub can than be assembled and fused to form a wax compressor wheel pattern. However, it is difficult to assemble a compressor pattern from separate wax parts with the required degree of precision—including coplanerism of airfoils, proper angle of attack or twist, and equal spacing. Further, stresses are encountered during assembling lead to distortion after removal from the assembly fixture. Finally, this is a labor intensive and thus expensive process. This technique cannot be employed on an industrial scale.
[0023] Certainly, titanium compressor wheels would seem desirable over aluminum or steel compressor wheels. Titanium is strong and light-weight, and thus lends itself to producing thin, light-weight compressor wheels which can be driven at high RPM without over-stress due to centrifugal forces.
[0024] However, as discussed above, titanium is one of the most difficult materials to work with, resulting in a prohibitively high cost of manufacturing compressor wheels. This manufacturing cost prevents their wide-spread employment. No new technology will be adopted industrially unless accompanied by a cost benefit.
[0025] There is thus a need for a simple and economical method, for mass producing titanium compressor wheels, and for the low-cost titanium compressor wheels produced thereby. The method must be capable of reliably and reproducibly producing compressor wheels, without suffering from the prior art problems of dimensional or structural imperfections, particularly in the thin blades.
SUMMARY OF THE INVENTION
[0026] The present invention addressed the problem of whether it would be possible to design a titanium compressor wheel for boosting air pressure and throughput to an internal combustion engine and satisfying the following two (seemingly contradictory) requirements:
aerodynamically: the aerodynamic efficiency, when operating at the high RPM at which titanium compressor wheels are capable of operating, must be comparable to the efficiency of the complex state-of-the-art compressor wheel designs, and manufacturability: the compressor wheels must be capable of being mass produced in a manner that is more efficient than the conventionally employed methods described above.
[0029] The problem was solved by the present inventors in a surprising manner. Simply stated, the present inventors approached this problem by standing it on it's head. Traditionally, a manufacturing process begins by designing a product, and then devising a processes for making that product. Most compressor wheels are designed for optimum aerodynamic efficiency, and thus have narrow blade spacing and complex leading and trailing edge design (excess rake, undercutting and backsweep, complex bowing and leading edge hump and dip).
[0030] The present invention was surprisingly made by departing from the conventional engineering approach and by looking first not at the end product, but rather at the various processes for producing the wax pattern. The inventors then designed various compressor wheels on the basis of “pullability”—ability to be manufactured using die inserts which are pullable—and then tested the operational properties of various compressor wheels produced from these simplified patterns at high RPM, with repeated load cycles, and for long periods of time (to simulate long use in practical environment). The result was a simplified compressor wheel design which (a) lends itself to economical production by casting of titanium, and (b) at high RPM has an entirely satisfactory aerodynamic performance.
[0031] More specifically, the invention provides a titanium compressor wheel with a simplified blade design, which will aerodynamically have a degree of efficiency comparable to that of a complex compressor wheel blade design, and yet which, form a manufacturing aspect, can be produced economically in an investment casting process (lost wax process) using a wax pattern easily producible at low cost from an automated (and “pullable”) die.
[0032] As a result of this discovery, the economic equation has shifted for the first time in favor of the titanium compressor wheel for general automotive technology.
[0033] Accordingly, in a first embodiment, the invention concerns a compressor wheel of simplified, blade design, such that:
a wax pattern can be formed in a die consisting of one or more die inserts per compressor wheel air passage (i.e., the space between the blades), and preferably two die inserts per air passage, and the die inserts can automatically be extracted radially or along some compound curve or axis in order to expose the wax pattern for easy removal.
[0036] The compressor wheel blades may have curvature, and may be of any design so long as the blade leading edges have no dips and no humps, and the blades have no undercut recesses and/or back tapers created by the twist of the individual air foils with compound curves of a magnitude which would prevent extracting the die inserts radially or along some curve or arc in a simple manner.
[0037] In simplest form, the wax mold is produced from a die having one die insert corresponding to each air passage. This is possible where the blades are designed to permit, pulling of simple die inserts (i.e., one die insert per air passage). However, as discussed below, teach die can be comprised of two or more die inserts, with two inserts per air passage being preferred for reasons of economy.
[0038] In a more advanced form, the blades are designed with some degree of rake or backsweep or curvature, but only to the extent that two or more, preferably two inserts, per air passage can be easily automatically extracted. Such an arrangement, though slightly increasing the cost and complexity of the wax mold tooling, would permit manufacture of wax molds, and thus compressor wheels, with greater complexity of shape. In the case of two inserts per air passage, the pull direction would not necessarily be the same for each member of the pair of inserts. The one die insert, defining one area of the air passage between two blades, may be pulled radially with a slight forward tilt, while a second die insert, defining the rest of the passage, may be pulled along a slight arc due to the slight backsweep of the blade. This embodiment is referred to as a “compound die insert” embodiment. One way of describing pullability is that the blade surfaces are not convex. That is, a positive draft exists along the pull axis.
[0039] Once the wax pattern is formed, the titanium investment casting process continues in the conventional manner.
[0040] The invention further concerns an economical method for operating an internal combustion engine, comprising providing said engine with an easily manufactured, long-life titanium compressor wheel and driving the titanium compressor wheel at high RPM for increasing combustion air throughput and density and reducing emissions.
[0041] The titanium compressor wheel of the present invention has a design lending itself to being produced in a simplified, highly automated process.
[0042] The foregoing has outlined rather broadly the more pertinent and important features of the present invention in order that the detailed description of the invention that follows may be better understood, and so that the present contribution to the art can be more fully appreciated. Additional features of the invention will be described hereinafter, which form the subject of the claims of the invention, it should be appreciated by those skilled in the art that the conception and the specific embodiments disclosed may be readily utilized as a basis for modifying or designing other compressor wheels for carrying out the same purposes of the present invention, it should also be realized by those skilled in the art that such equivalent structures do not depart from the spirit and scope of the invention as set forth in the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0043] For a fuller understanding of the nature and objects of the present invention reference should be made by the following detailed description taken in with the accompanying drawings in which:
[0044] FIG. 1 shows a compressor wheel of prior art design in elevated perspective view;
[0045] FIG. 2 shows, in comparison to FIG. 1 , a compressor wheel designed in accordance with the present invention, in elevated perspective view;
[0046] FIG. 3 shows a partial compressor wheel of prior art design in side profile view;
[0047] FIG. 4 shows, in comparison to FIG. 3 , a partial compressor wheel designed in accordance with the present invention, in side profile view;
[0048] FIG. 5 shows an enlarged partial section of a compressor wheel of prior art design in elevated perspective view;
[0049] FIG. 6 shows, in comparison to FIG. 5 , an enlarged partial section of a compressor wheel designed in accordance with the present invention, in elevated perspective view;
[0050] FIG. 7 shows a simplified section, perpendicular to the rotation axis of the compressor wheel, with die inserts defining the hub and blades of a compressor wheel;
[0051] FIG. 8 corresponds to FIG. 7 and shows a top view onto a compressor wheel sectioned perpendicular to the rotation axis at about the center of the hub;
[0052] FIGS. 9 and 10 show a simplified arrangement for extracting a die along a simple curve;
[0053] FIG. 11 shows a compressor wheel according to the invention, with slightly backswept trailing edge, for production using compound die inserts.
DETAILED DESCRIPTION OF THE INVENTION
[0054] One major aspect of the present invention is based on an adjustment of an aerodynamically acceptable design or blade geometry so as to make a wax pattern, from which the cast titanium compressor wheel is produced, initially producible in an automatic die as a unitized, complete shape. The invention provides a simplified blade design which (a) allows production of wax patterns using simplified tooling and (b) is aerodynamically effective. This modified blade design is at the root of a simple and economical method for manufacturing cast titanium compressor wheels.
[0055] The invention provides for the first time a process by which titanium compressor wheels can be mass produced by a simple, low cost, economical process. In the following the invention will first be described using simple die inserts, i.e., one die insert per air passage, after which an embodiment having compound die inserts, i.e., two or more die inserts per air passage, will be described.
[0056] The term “titanium compressor wheel” is used herein to refer to a compressor wheel comprised predominantly of titanium. One example of a suitable titanium alloy consists of 90% titanium, 6% aluminum, and 4% vanadium. This is often simply referred to in the art as titanium, but is more accurately a “titanium alloy”, and these terms are used interchangeably herein.
[0057] As the starting point for understanding the present invention, it must be understood that the shape, contours and curvature of the blades are modified to provide a design which, on the one hand, provides aerodynamically acceptable characteristics at high RPM, and on the other hand, makes it possible to produce a wax pattern economically using an automatic compound die. That is, it is central to the invention that die inserts used to define the air passages during casting of the wax pattern are “pullable”, i.e., can be withdrawn radially or along a curvature in order to make the die inserts retractable, the following aspects were taken into consideration:
the compressor wheel must have adequate blade spacing; the compressor wheel may not exhibit excess rake and/or backsweep of the blade leading edge or trailing edge, there may not be excessive twist in the blades, there may be no dips or humps along the leading edge of the blade which would prevent pulling of the die inserts, there may not be excessive bowing of the blade, and the die inserts used in forming the wax pattern must be extractable along a straight line or a simple curve.
[0064] Once the wax pattern satisfying the above requirements has been produced, the remainder of the casting technique can be traditional investment casting, with modifications as known in the art for casting titanium. A wax pattern is dipped into a ceramic slurry multiple times. After a drying process the shell is “de-waxed” and hardened by firing. The next step involves filling the mold with molten metal. Molten titanium is very reactive and requires a special ceramic shell material with no available oxygen. Pours are also preferably done in a hard vacuum. Some foundries use centrifugal casting to fill the mold. Most use gravity pouring with complex gating to achieve sound castings. After cool-down, the shell is broken and removed, and the casting is given special processing to remove the mold-metal reaction layer, usually by chemical milling.
[0065] Some densification by HIP (hot isostatic pressing) may be needed if the process otherwise leaves excessive internal voids.
[0066] The invention will now be described in greater detail by way of comparing the compressor wheel of the invention to a compressor wheel of the prior art, for which reference is made to the figures.
[0067] FIGS. 1 and 3 show a prior art compressor wheel 1 , comprising an annular hub 2 which extends radially outward at the base part to form a base 3 . The transition from hub to base may be curved (fluted) or may be angled. A series of evenly spaced thin-walled full blades 4 and “splitter” blades 5 are form an integral part of the compressor wheel. Splitter blades differ from full blades mainly in that their leading edge begins further axially downstream as compared to the full blades. The compressor wheel is located in a compressor housing, with the outer free edges of the blades passing close to the inner wall of the compressor housing. As air is drawn into the compressor inlet, passes through the air channels of the rapidly rotating compressor wheel, and is thrown (centrifugally) outwards along the base of the compressor wheel into an annular volute chamber, and this compressed air is then conveyed to the engine intake. It is readily apparent that the complex geometry of the compressor wheel, with dips 6 and humps 7 along the blade leading edge, undercut recesses 9 created by the twist of the individual air foils with compound curves, and rake or back tapers (back sweep) 8 at the blade trailing edge, would make it impossible to cast such a shape in one piece in an automatic process, since the geometry would impede the withdrawal of die inserts or mold members.
[0068] FIGS. 2 and 4 , in comparison, show a compressor wheel according to the present invention, designed beginning foremost with the idea of making die inserts easily retractable, and thus taking into consideration the interrelated concepts of adequate blade spacing, absence of excess rake and/or backsweep of the blade leading edge and trailing edge, absence of dips or humps along the leading edge, and extractability of die inserts along a straight line or a simple curve. Simply stated, the main characterizing feature of the present invention is the absence of blade features which would prevent “pullability” of die inserts.
[0069] These design considerations result, as seen in FIGS. 2 and 4 , in a compressor wheel 11 (the wax pattern being identical in shape to the final titanium product, the figures could be seen as showing either the wax pattern or the cast titanium compressor wheel) with a hub 12 having a hub base 13 , and a series of evenly spaced thin walled full blades 14 and “splitter” blades 15 cast as an integral part of the compressor wheel.
[0070] It can be seen that the leading edge 17 of the blades are essentially straight, having no dips or humps which would impede radial extraction of die inserts. That is, there may be a slight rounding up 18 (i.e., continuation of the blade along the blade pitch) where the blade joins the hub, but this curvature does not interfere, with pullability of die inserts.
[0071] It can be seen that the blade spacing is wide enough and that any rake and/or backsweep of the blades is not so great as to impede extraction of the inserts along a straight line or a simple curve.
[0072] Trailing edge 16 of the blade 14 may in one design extend relatively radially outward from the center of the hub (the hub axis) or, more preferably, may extend along an imaginary line from, a point on the outer edge of the hub disk to a point on the outer (leading) circumference of the hub shaft. The trailing edge of the blade, viewed from the side of the compressor wheel may be oriented parallel to the hub axis, but is preferably cantilevered beyond the base of the hub and extends beyond the base triangularly, as shown in FIG. 2 , and is inclined with a pitch which may be the same as the rest of the blade, or may be increased. Finally, as shown in FIG. 11 , the blade may have a small amount of backsweep (which, when viewed with the forward sweep of the leading edge, produced a slight “S” shape) but the area of the blade near the trailing edge is preferably relatively planar.
[0073] In a basic embodiment, the compressor wheel has from 8 to 12 full blades and no splitter blades. In a preferred embodiment, the compressor wheel has from 4 to 8, preferably 6, full blades and an equal number of splitter blades.
[0074] FIG. 3 shows a partial compressor wheel of prior art design in side profile view, with the blade leading edge exhibiting a dip 6 and a hump 7 producing a shape which would interfere with radial extraction of die inserts.
[0075] FIG. 4 shows a partial compressor wheel similarly dimensioned to the wheel of FIG. 3 , but as can be seen, with a substantially straight shoulder of the blade from neck 18 to tip 19 .
[0076] FIG. 5 shows an enlarged partial section of a compressor wheel of a prior art design in elevated perspective view, illustrating dip 6 , hump 7 , and bowing and curvature of the leading edge. It can also be seen that the “twist” (difference in pitch along the leading edge), in addition to the curvature, would make it impossible to radially extract a die insert.
[0077] FIG. 6 shows an enlarged partial section of a partial compressor wheel according to the invention, similarly dimensioned to FIG. 5 , but designed in accordance with the present invention, showing a straight leading edge 19 and an absence of any degree of twist and curvature which would prevent pulling of die inserts.
[0078] Obviously, the above dimensions refer equally to the wax pattern and the finished compressor wheel. The wax pattern differs from the final product mainly in that a wax funnel is included. This produces in the ceramic mold void a funnel into which molten metal is poured during casting. Any excess metal remaining in this funnel area after casting is removed from the final product, usually by machining.
[0079] In FIG. 7 the tool or die for forming the wax form is shown in closed condition, in sectional view along section line 8 shown in FIG. 6 , and simplified (omitting mechanical extraction means, etc.) for better understanding of the essential feature of the invention, revealing a cross section through a compressor wheel shaped mold. The mold defines a hub cavity and a number of inserts 20 that occupy the air passages between the blades, thus defining the blades, the walls of the hub, and the floor of the air passage at the base of the hub. With these inserts in place as shown in FIG. 7 , molten wax is poured into the die. The wax is allowed to cool and the individual inserts 20 are automatically extracted radially as shown in FIG. 8 or along some simple or compound curve as shown in FIGS. 9 and 10 in order to expose the solid wax pattern 21 and make possible the removal of the pattern from the die. FIGS. 7 and 8 illustrate radial extraction. FIGS. 9 and 10 in comparison illustrate extraction along a simple curve, using offset arms 22 .
[0080] FIGS. 7-10 show 6 dies and 6 blades for ease of illustration; however, as discussed above, the die preferably has a total of either 12 (simple) or 24 (compound) inserts for making a total of 6 full length and 5 “splitter” blades. As discussed above, in the case of 24 compound inserts, one set of 12 corresponding inserts is first extracted simultaneously, and then the second sat of 12 corresponding inserts is extracted simultaneously. Compound die inserts can be produced by dividing the air cavity into two sections, and either die insert can be extracted radially or along a curve, depending upon blade design.
[0081] The wax casting process according to the invention occurs fully automatically. The inserts are assembled to form a mold, wax is injected, and the inserts are timed by a mechanism to retract in unison.
[0082] Once the wax pattern (with pour funnel) is formed, the ceramic mold forming process and the titanium casting process are carried out in conventional manner. The wax pattern with pour funnel is dipped into a ceramic slurry, removed from the slurry and coated with sand or vermiculite to form a ceramic layer on the wax pattern. The layer is dried, and the dipping, sanding and drying operations are repeated several times to create a multiple layer ceramic shell mold enclosing or encapsulating the combined wax pattern. The shell mold and wax patterns with pour funnel are then placed within a kiln and fired to remove the wax and harden the ceramic shell mold with pour funnel.
[0083] Molten titanium is poured into the shell mold, and after the titanium hardens, the shell mold is removed by destroying the mold to form a light weight, precision case compressor wheel capable of withstanding high RPM and high temperatures.
[0084] The titanium compressor wheel of the present invention has a design lending itself to being produced in a simplified, highly automated process. As a result, the compressor wheel is not liable to any deformities as might result when using em elastic deformable mold, or when assembling separate blades onto a hub, according to the procedures of the prior art.
[0085] Tested against an aluminum compressor wheels of similar design, the aluminum compressor wheel as not capable of withstanding repeated exposure to higher pressure ratios, while the titanium compressor wheel showed no signs of fatigue even when run through thirteen or more times the number of operating cycles as the aluminum compressor wheel.
[0086] Although this invention has been described in its preferred form with a certain degree of particularity with respect to a titanium compressor wheel, it is understood that the present disclosure of the preferred form has been made only by way of example and that numerous changes in the details of structures and the composition of the combination may be resorted to without departing from the spirit and scope of the invention.
[0087] FIG. 11 shows a compressor wheel which corresponds essentially to the compressor wheel of FIG. 2 , except that a modest amount of backsweep is provided at the trailing edge 16 of the blade. This small amount of backsweep, taken with the forward rake along the leading edge of the blade, might make it difficult to easily extract a single die insert defining an entire air passage. To facilitate die insert removal, the compressor wheel shown in FIG. 11 can be produced using compound die inserts, i.e., a first die insert for defining the initial or inlet area of the air passage, and a second die insert for defining the remaining air passage area. The manner in which the air passage is divided into two areas is not particularly critical, it is merely important that the first and second die insert can be withdrawn either simultaneously or sequentially.
[0088] Although a cast titanium compressor wheel has been described herein with great detail with respect to an embodiment suitable for the automobile or truck industry, it will be readily apparent that the compressor wheel and the process for production thereof are suitable for use in a number of other applications, such as fuel cell powered vehicles. Although this invention has been described in its preferred form with a certain of particularity with respect to an automotive internal combustion compressor wheel, it is understood that the present disclosure of the preferred form has been made only by way of example and that numerous changes in the details of structures and the composition of the combination may be resorted to without departing from the spirit and scope of the invention.
[0089] Now that the invention has been described.
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An air boost device such as a turbocharger, wherein the compressor wheel thereof is re-designed to permit die inserts ( 20 ), which occupy the air passage and define the blades ( 4, 5 ) during a process of forming a wax pattern ( 21 ) of a compressor wheel, to be pulled without being impeded by the blades. This modified blade design enables the automated production of wax patterns ( 21 ) using simplified tooling. The compressor wheel improves low cycle fatigue, withstands high temperatures and temperature changes, and permits operation at high boost pressure ratio while, on the other hand, having low weight, low inertial drag, and high responsiveness.
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BACKGROUND OF THE INVENTION
The present invention relates to an agent for bloat-prevention or -treatment. Further, the present invention relates to an agent for bloat-prevention or -treatment which comprises at least a saccharide fatty acid ester and fatty acid salt.
Bloat is a disease wherein the rumen and a reticulum of a ruminant, for example, cattle, sheep etc. distend severely due to the fermentative gas accumulating therein. Bloat is one of the most horrible diseases in feeding beef cattle, dairy cattle, sheep etc., because ruminants affected with bloat fall into a state of inappetence resulting in the reduction in growth rate or milk yield and, to cite an extreme case, they are suffocated to death.
Though there have been various theories in relation to the cause of bloat, the established theory is today that the feeding of large quantities of legume pasture, or the feeding of large quantities concentrate feed etc. cause bloat. Namely, it is considered as follows: Much legume pasture being fed, the contents of a rumen become liable to foam owing to the actions of foaming substances, such as saponin, vegetable protein etc., contained in a legume pasture, and a roughage being fed insufficiently and much concentrate feed being fed, an abnormal fermentation in the rumen, the viscosity increase of the liquid contained therein, etc., become liable to occur, so that in both cases the exhaustion of gas by eructation is impeded resulting in the excessive distensions of the rumen and the reticulum.
There are known methods for preventing or treating bloat as follows: (1) a method in which much oil is sprinkled on a pastureland; (2) a method in which the amount of a roughage used together with a concentrate feed is kept proper; (3) a method wherein there is used every time a drinking water or a mineral block to which has been added a defoaming agent, for example, silicone, polypropylene glycol (another name: polyoxypropylene glycol), polyoxypropylene/polyoxyethylene block-copolymer; (4) a treating method in which a stomach catheter or a trocar is used for exhausting gas and (5) a treating method employing the administration of much defoaming agent, for example, silicone, polypropylene glycol, polyoxypropylene/polyoxyethylene block-copolymer, mineral oil, vegetable oil etc. However, these methods have respectively the following disadvantages as follows: Namely, the method (1) requires much labor and is not economical, because of sprinkling oil on a large pastureland, and the method (2) has the problem that this method is inconsistent with the system for fattening beef cattle rapidly by feeding much concentrate feed, said system being employed in Japan etc., and it is difficult to achieve excellent results by this method, and the method (4) requires an expert and attended with a strong possibility of the relapse being repeated so long as the cause of bloat is not removed; and though the methods (3) and (5) can show a considerable good effect, the problem in using most defoaming agents known today is that they cause digenstion disturbance owing to the long continuous administration of a defoaming agent, or owing to the administration of much defoaming agent being done at a time. Accordingly, it is today expected that agents with better efficiencies in defoaming effect, etc. and with an improved safety will be produced.
SUMMARY OF THE INVENTION
In consideration of such circumstances as described above, the present inventors have continued research and attained the facts that a mixture comprising at least saccharide fatty acid ester and fatty acid salt has various effects, such as an excellent defoaming effect, the effect lowering the viscosity of a rumen juice, the effect hightening the pH value of said juice, etc., and is further very safe for the living body, so that such a mixture is suitable as an agent for bloat-prevention or -treatment. The facts described above produced the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The animals intended by the agent for bloat-prevention or -treatment of the present invention are ruminants, such as beef cattle, dairy cattle, young cattle, sheep, goats, etc.
Saccharide fatty acid esters being used for the present invention are the fatty acid esters of saccharides, to give typical examples, arabinose, xylose, ribose, lyxose, ribulose, xylulose, glucose, galactose, talose, mannose, fructose, sorbose, tagatose, psicose, maltose, isomaltose, cellobiose, gentiobiose, trehalose, lactose, sucrose, maltotriose, gentianose, raffinose, stachyose, etc. Monoesters, polyesters, such as diesters, triesters, tetraesters etc. and the mixtures of two or more of them are usable. Monoester have one ester linkage in one molecule of saccharide fatty acid ester; polyesters have two or more ester linkages in one molecule of saccharide fatty acid ester.
Among the saccharide fatty acid esters described above, sucrose fatty acid esters are examples of the saccharide fatty acid esters which are most suitable in the present invention, since they are easily available and also considerably low-priced owing to the industrial mass-productions.
The fatty acids with about 6-24 carbons are usually suitable as the fatty acid part of saccharide fatty acid ester. Both saturated and unsaturated fatty acids are usable. Both fatty acids with a straight carbon chain and fatty acids with a branched carbon chain are usable. Further, fatty acids with one or more of substituents, such as a hydroxyl group, etc., are usable. Fatty acids are not necessarily monobasic acids, and dibasic acids, etc. are also usable.
Further, fatty acids are not restricted to the fatty acids from natural materials, such as oils or fats, etc. Synthetic fatty acids are also usable which are produced by the liquid-phase catalytic oxidations of paraffins, the carbonylations of α-olefins (oxo method), the carboxylations of branched olefins (Koch's method) or other methods.
The typical examples of such fatty acids are enumerated as follows: caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, lauric acid, tridecanoic acid, 2-methlyltetradecanoic acid, 5-methyltetradecanoic acid, 2,2-dimethyltetradecanoic acid, myristic acid, palmitic acid, margaric acid, stearic acid, arachic acid, behenic acid, lignoceric acid, oleic acid, elaidic acid, linoleic acid, linolenic acid, ricinoleic acid, arachidonic acid, eicosapentaenoic acid, erucic acid, azelaic acid, sebacic acid, 1,20-eicosamethylenedicarboxylic acid, etc.
The saccharide fatty acid esters described above are not necessarily used respectively alone, and the mixtures of two or more kinds of saccharide fatty acid esters of which the saccharide parts are different or of which the fatty acid parts are different or of which the numbers of the ester linkages are different, are also usable in any mixing ratio.
On the other hand, the other component being used for the present invention is fatty acid salt. The typical examples of fatty acid salts are the salts of various fatty acids described above, enumerated as follows: alkali metal salts, such as lithium salts, sodium salts, potassium salts, etc.; alkaline earth metal salts, such as magnesium salts, calcium salts, barium salts, etc.; various metal salts, such as zinc salts, aluminum salts, iron salts, manganese salts, etc.; ammonium salts; organoamine salts, such as monoethanolamine salts, diethanolamine salts, triethanolamine salts, etc.; basic amino acid salts, such as lysine salts, ornithine salts, arginine salts, histidine salts, hydroxylysine salts, etc., and most of all, alkali metal salts, ammonium salts and basic amino acid salts are most generally used.
As described above in relation to saccharide fatty acid esters, the fatty acid salts described above are respectively usable alone and the mixtures of two or more kinds of fatty acid salts of which the fatty acid parts are different or of which the cation parts are different, are also usable as in the case of using one salt alone.
Such saccharide fatty acid esters and fatty acid salts can be easily produced by known methods, and ones produced by any method are usable in the present invention.
The typical examples of processes for preparing saccharide fatty acid esters are enumerated as follows: (1) saccharide and fatty acid lower-alkyl ester, for example, fatty acid methyl ester, fatty acid ethyl ester, etc. are subjected to the alcoholysis using fatty acid salt, for example, fatty acid sodium salt, fatty acid potassium salt, etc. and a basic catalyst in the presence of water or very safe solvent, for example, propylene glycol, etc.; (2) saccharide and fatty acid methyl ester, fatty acid carbitol ester or fatty acid glyceride (mono-, di- and triglyceride), etc. are subjected to alcoholysis in the presence of fatty acid salt, for example, fatty acid sodium salt, fatty acid potassium salt, etc.; (3) saccharide and fatty acid lower-alkyl ester, or oil or fat (that is, fatty acid triglyceride) are subjected to alcoholysis in the presence of a basic catalyst; (4) saccharide is reacted with fatty acid chloride or fatty acid anhydride.
Among these processes, (1), (2) and (3) are very advantageous, because the crude products prepared by these processes contain saccharide fatty acid ester and fatty acid salt (usually, fatty acid alkali metal salt) and can be economically produced and are usable in the present invention without purification, namely, as they are.
On the other hand, fatty acid salts can be easily produced by reacting fatty acid or fatty acid ester, for example, fatty acid methyl ester, fatty acid ethyl ester, fatty acid glyceride, etc. with oxide, hydroxide, carbonate or hydrogen carbonate of alkali metal or alkaline earth metal, etc., basic amino acid, ammonia or organoamine, etc., or by other methods.
The fatty acid salts produced in advance by the above-described methods, etc. are not necessarily used. For example, it is employable to treat as follows: fatty acid and oxide, hydroxide, carbonate or hydrogen carbonate of alkali metal or basic amino acid, etc. are used in the free state each so that fatty acid salt will be prepared in the agent for bloat-prevention or -treatment of the present invention. Employing such methods is within the spirit and scope of the present invention claimed.
The suitable use amount ratio by weight of saccharide fatty acid ester to fatty acid salt in the agent for bloat-prevention or -treatment of the present invention is usually approximately in the range of 97:3 to 3:97, preferably 95:5 to 5:95, most preferably 90:10 to 10:90.
In the present invention it is not required necessarily that the saccharide fatty acid esters and the fatty acid salts be purified to a high degree. In the present invention it is permissable to use the saccharide fatty acid esters and the fatty acid salts accompanied by one or more of the substances highly safe for the living body, such as saccharides, fatty acid lower-alkyl esters, fatty acid glycerides (mono-, di- and triglyceride), fatty acids, alkali metal carbonates, basic amino acids etc. which remain owing to partial unreaction or may remain in the production of saccharide fatty acid ester or fatty acid salt as in the case of the crude saccharide fatty acid ester described above, and byproducts, such as alcohol, glycerin, etc.
The agent for bloat-prevention or -treatment of the present invention is usable in optional forms, such as powder, granule, pellet, crumble, cube, tablet, half-wetted, paste, aqueous solution, aqueous suspension, etc.
The various forms described above being prepared, the following materials may be used as a diluting agent: water; wheat flour, starch, dextrin; feed materials being widely used, for example, cereal grains, such as corn, milo (kaoliang), etc.; chaffs and brans, such as rice bran, deoiled rice-bran, wheat bran, etc.; oil seed meals, such as soybean meal, rape seed meal, cotton seed meal, linseed meal, etc.; oils or fats, such as beef tallow, soybean oil, palm oil, coconut oil, fish oil, etc.
When the agent for bloat-prevention or -treatment of the present invention is administered into animals, the agent for bloat-prevention or -treatment with a form described above is administered apart from a drinking water and a feed, or may be compulsorily injected into a rumen, and however, is most conveniently added into a drinking water or added into a feed to be given to animals. In the feeding system using principally a pasture grass, the present agent may be sprinkled on pasture grasses.
Though the use amount of the agent for bloat-prevention or -treatment of the present invention can not be uniformly fixed because of varying with the factors, such as the kinds, the ages, the body weights, etc. of intended animals, the proper use of the present agent, namely, as an agent for prevention or as an agent for treatment, administration methods, the extent of bloat, the kinds of feeds, etc., the total use amount of saccharide fatty acid ester and fatty acid salt is usually, when being added into a drinking water or a feed to be given to animals, approximately 0.005-10% by weight, preferably 0.01-5% by weight, most preferably about 0.02-3% by weight to the amount of the drinking water or the feed (each containing ingredients other than saccharide fatty acid ester and fatty acid salt) being finally given to animals. In the case that the use amounts described above are less than the lowest limit values, it becomes difficult to show sufficiently the effect of the present invention, and the uses of the amounts exceeding the highest limit values described above do not show any specific effect and are rather uneconomical, so that such uses are not desirable. Using the present agent as an agent for prevention can show a sufficient effect by a continuous administration even if in a relatively low concentration, and using the present agent as an agent for treatment can show the effect of the present invention in a short period by employing a higher concentration than in using the present agent as an agent for prevention.
The agent for bloat-prevention or -treatment of the present invention is usually used alone and can be naturally used together with a known defoaming agent, for example, silicone, polypropylene glycol, polyoxypropylene/polyoxyethylene block-copolymer, oil or fat, etc. or other agents.
Having a much more excellent defoaming effect than conventional agents, the agent for bloat-prevention or -treatment of the present invention can prevent the foaming of the rumen juice of a ruminant and can change a foamed rumen juice into a normal rumen juice. Describing in passing, saccharide fatty acid ester and fatty acid salt have respectively a considerable good defoaming effect (proviso: when saccharide fatty acid ester is not used in rich amount, the defoaming effect is insufficient). However, the combination use of the both can show a very excellent defoaming effect owing to the synergism. The defoaming effect can be more heightened by using saccharide fatty acid ester and fatty acid salt together with fatty acid glyceride, for example, oil or fat (namely, fatty acid triglyceride), fatty acid monoglyceride, fatty acid diglyceride etc. or propylene glycol fatty acid ester, etc.
And, the agent for bloat-prevention or -treatment of the present invention shows the effect which facilitates exhausting immediately the gas produced in a rumen out of the body, because of the effect lowering a stable ingesta volume increase value which is used as a criterion for examining how hard or easy the exhaustion of the fermentative gas produced in a rumen is (the lowering of said value means that the exhaustion of the gas becomes easy), or because of the effect lowering the viscosity of a rumen juice.
Further, the agent for bloat-prevention or -treatment of the present invention has the effect raising the pH value of a rumen juice to the desired degree. The pH value of the rumen juice of a healthy ruminant is usually about 6.5-7.5. However, when much concentrate feed has been fed or when bloat has been induced by an abnormal fermentation, etc. in a rumen, it is frequently observed that the pH value is liable to be lowered (there are various types of bloats, so that certain bloats show the almost same pH value as in a healthy state) and it is not seldom that the pH value lowers down to a pH value of about 4-5. Further, the extreme lowering of the pH value of a rumen juice is a serious problem, because such a extremely-lowered pH value is apt to kill microorganisms in a rumen, such as bacteria, protozoa, etc.
The agent of the present invention shows the effect raising the pH value of a rumen juice to the desired degree by which the environment suitable for the microorganisms in a rumen is kept or recovered, and shows the effect for preventing or treating bloat together with the defoaming effect, etc. described above.
Furthermore, the agent for bloat-prevention or -treatment of the present invention is very safe for the living body and is also easily metabolized in the living body. Therefore, a long continuous administration into an animal and administration of much amount being done at a time do not become a problem in point of safety at all.
As described above, the agent for bloat-prevention or -treatment of the present invention has various effects, such as an excellent defoaming effect, the effect lowering the viscosity of the rumen juice of a ruminant, the effect raising the pH value to the desired degree etc. and has an excellent safety, and therefore has a high practical value as an agent for bloat-prevention or -treatment.
Furthermore, the present invention is in detail explained by means of examples, controls and references hereinafter.
EXAMPLES 1-14
In order to examine artificially the administration effect especially the defoaming effect, of the agent for bloat-prevention or -treatment of the present invention on bloat being frequently induced by the feeding of much leguminous pasture, the various agents for bloat-prevention or -treatment of the present invention comprising respectively at least saccharide fatty acid ester and fatty acid salt, shown in Table 1, were respectively added into an aqueous saponin solution of 0.25% by weight so as to become the respective specified concentration (shown in Table 1) in the resulting solution and the foamabilities of the resulted solutions were determined (proviso: in each case of examples 11-14, the crude products prepared by reaction and containing fatty acid glyceride, sucrose, glycerin, etc. besides saccharide fatty acid ester and fatty acid salt, was added and examined). The results are shown in Table 1. The method for measuring the foamability is shown as follows:
METHOD FOR MEASURING A FOAMABILITY
The agent for bloat-prevention or -treatment of the present invention is added into an aqueous solution of 0.25% by weight in each specified amount and mixed. Just and five minutes after the foaming treatment at 25° C. or 40° C. according to Ross & Miles's method (Japanese Industrial Standard JIS K 3362), the resulted foam height (mm) is measured.
CONTROLS 1 AND 2
The foamability of only the aqueous saponin solution of 0.25% by weight with no agent for bloat-prevention or -treatment of the present invention was measured in each control in the same manner as used in examples 1-14 (the measurement temperature: 25° C. in control 1; 40° C. in control 2). The results were shown in Table 1.
CONTROL 3
Only saccharide fatty acid ester was added into an aqueous saponin solution of 0.25% by weight and the foamability of the resulted solution was measured in the same manner as used in examples 1-14 (the measurement temperature: 25° C.). The results were shown in Table 1.
CONTROL 4
Only fatty acid salt was added into an aqueous saponin solution of 0.25% by weight and the foamability of the resulted solution was measured in the same manner as used in examples 1-14 (the measurement temperature: 25° C.). The results were shown in Table 1.
TABLE 1__________________________________________________________________________The composition and the use amount of the agent for bloat-prevention or -treatment of the present inventionSaccharide fatty acid ester Fatty acid salt Foamability Conc. Conc. (mm)Example (% by (% by Measurement Fiveor weight) weight) temperature Just minutesControlKind (Note 1) Kind (Note 2) (°C.) after after__________________________________________________________________________ExampleSucrose hydrogenated 0.20 Stearic acid 0.05 25 23 201 beef tallow fatty potassium saltacid ester mono-: 70% by w.di-: 30% by w. ExampleSucrose hydrogenated 0.20 Stearic acid 0.05 40 22 192 beef tallow fatty potassium saltacid ester mono-: 70% by w.di-: 30% by w. ExampleSucrose hydrogenated 0.05 Stearic acid 0.20 25 23 213 beef tallow fatty potassium saltacid ester mono-: 70% by w.di-: 30% by w. ExampleSucrose hydrogenated 0.05 Stearic acid 0.20 40 24 224 beef tallow fatty potassium saltacid ester mono-: 70% by w.di-: 30% by w. ExampleSucrose hydrogenated 0.033 Stearic acid 0.017 25 21 185 beef tallow fatty potassium saltacid ester mono-: 70% by w.di-: 30% by w. ExampleSucrose hydrogenated 0.017 Stearic acid 0.033 25 23 206 beef tallow fatty potassium saltacid ester mono-: 70% by w.di-: 30% by w. ExampleSucrose hydrogenated 0.20 Coconut fatty acid 0.05 25 16 127 beef tallow fatty sodium saltacid ester mono-: 70% by w.di-: 30% by w. ExampleSucrose beef tallow 0.05 Palmitic acid L- 0.05 25 25 208 fatty acid ester lysin saltmono-: 65% by w di-: 30% by w.tri-: 5% by w.ExampleRaffinose beef 0.15 Oleic acid sodium 0.10 40 14 99 tallow fatty acid saltestermono-: 60% by w. di-: 30% by w.tri-: 10% by w.ExampleMaltotriose mono- 0.10 Beef tallow fatty 0.05 40 20 1510 palmitic acid ester acid sodium salt ExampleThe crude products prepared (Note 3) by subjecting 25crose 0 011 and beef tallow to the alcoholysis using potassiumcarbonate as a catalyst was added so as to become 0.25%by weight.ExampleThe crude products prepared (Note 3) by subjecting 40crose 0 012 and beef tallow to the alcoholysis using potassiumcarbonate as a catalyst was added so as to become 0.25%by weight.ExampleThe same crude products as used in examples 11 and 12 25s 11 013 added so as to become 0.05% by weight.ExampleThe same crude products as used in examples 11 and 12 40s 6 014 added so as to become 0.05% by weight.Control 25 220 195Control 40 228 2042ControlSucrose hydrogenated 0.05 25 56 453 beef tallow fattyacid ester mono-: 70% by w.di-: 30% by w.Control Stearic acid 0.05 25 212 1834 potassium salt__________________________________________________________________________ Notes 1 and 2. The both concentrations mean the concentrations of saccharide fatty acid ester and fatty acid salt in the solution prepared by being added into an aqueous saponin solution of 0.25% by weight (proviso: the concentration of the crude products prepared by reaction wa showed in each of examples 11-14). Note 3. The crude products prepared by reaction, said crude products comprising 30% by weight sucrose beef tallow fatty acid ester (monoester/diester = 65/35 weight ratio), 25% by weight beef tallow fatty acid potassium salt, 20% by weight beef tallow fatty acid glyceride (the total amount of mono, di and triglyceride) and 25% by weight others (sucrose, glycerin etc.), was used in examples 11-14.
REFERENCE 1
The commercially available agent for bloat-prevention (polyoxypropylene/polyoxyethylene block-copolymer, the molecular weight: 1250, the content of polyoxyethylene parts: 20%) was added into an aqueous saponin solution of 0.25% by weight so as to become 0.25% by weight in the resulting solution. The foamability of the resulted solution was measured in the same manner as used in examples 1-14 (the measurement temperature: 25° C.). The foamability was 65 mm just after the foaming treatment and 57 mm five minutes after the foaming treatment.
REFERENCE 2
The same commercially available agent for bloat-prevention as used in reference 1 was added into an aqueous saponin solution of 0.25% by weight so as to become 0.05% by weight in the resulting solution. The foamability was measured in the same manner as used in examples 1-14 (the measurement temperature: 25° C.). The foamability was 172 mm just after the foaming treatment and 152 mm five minutes after the treatment.
REFERENCE 3
The commercially available agent for bloat-prevention (polyoxypropylene/polyoxyethylene block-copolymer, the molecular weight: 2000, the content of polyoxyethylene parts: 50%) was added into an aqueous saponin solution of 0.25% by weight so as to become 0.25% by weight in the resulting solution. The foamability of the resulted solution was measured in the same manner as used in examples 1-14 (the measurement temperature: 25° C.). The foamability was 185 mm just after the foaming treatment and 168 mm five minutes after the foaming treatment.
EXAMPLES 15-17
It is shown by the under-described experiment that the fermentative gas is easily exhausted by adding the agent for bloat-prevention or -treatment of the present invention into the rumen juice of a ruminant.
EXPERIMENT METHOD
Rumen juice is collected from three sheep affected with bloat artificially by feeding the bloat-inducing feed (the feed described in "D. R. Jacobson et al., Journal of Animal Science, Vol. 16, pages 515-524 (1957)", said feed comprising 61% barley, 22% alfalfa meal, 16% soybean meal and 1% NaCl), and the mixture of the three rumen juices collected is used as the rumen juice for the present experiment.
Next, 200 ml of said mixture is poured into a 500 ml messcylinder and thereinto the agent for bloat-prevention or -treatment of the present invention is added in each specified amount and thereafter the resulting mixture is incubated at 39° C. for one hour in an incubator and further incubated with stirring by a glass rod every five minutes for one hour and the volume increase rate (%) of the rumen juice in the messcylinder is measured and the value of said rate is used as the stable ingesta volume increase (referred to as Stable IVI hereinafter). Stable IVI teaches that the smaller Stable IVI becomes, the easier exhausting the fermentative gas out of a rumen juice becomes.
EXPERIMENT CONDITIONS AND RESULTS
The experiment conditions and results are shown in Table 2. The agent for bloat-prevention or -treatment of the present invention which was used in the present experiment is the crude products prepared by subjecting sucrose and beef tallow to the alcoholysis using potassium carbonate as a catalyst and said crude products are the same as used in examples 11-14.
CONTROL 5
Stable IVI of only the rumen juice without the agent for bloat-prevention or -treatment of the present invention was measured in the same manner as used in examples 15-17. The result is shown in Table 2.
EXAMPLE 18
Eighteen Holstein bulls of eight weeks of age were divided into three groups respectively consisting of six Holstein bulls and the feeding trials were carried out by feeding the feeds with the respective composition shown in Table 3 to respective group for five weeks (namely, till thirteen weeks of age). Besides the respective feed with the composition shown in Table 3, dried grass was fed as a roughage to bulls of all groups at the rate of about 0.3 kg/bull/day (this amount corresponds to about one-tenth the feeding amount shown in Table 3). During the feed trials, the rumen juices of the bulls of all groups were collected at 10 and 13 weeks of age, and the viscosity and the pH value of each rumen juice were measured. The average viscosity and the average pH value of the bulls per group were calculated and shown in Table 3.
TABLE 2______________________________________Agent for bloat-prevention or -treatment ConcentrationExample to the rumenor juice Stable IVIControl Kind (% by weight) (%)______________________________________Example The same crude prod- 0.5 2115 ucts as used in examples 11-14Example The same crude prod- 1 1916 ucts as used in examples 11-14Example The same crude prod- 2 2017 ucts as used in examples 11-14Control 47______________________________________
TABLE 3______________________________________Group 1 2 3Division Test No. 1 Test No. 2 Control______________________________________Ingredients andmixing ratio (partsby weight) in eachgiven feedCommercially available 100 100 100feed for young cattle(Note 1)Agent for bloat- 1 0.2 0prevention ortreatment of thepresent invention(Note 2)State ofeach rumenjuiceViscosity 7.7 9.5 13.5(cp/25° C.)pH 7.1 6.7 6.5______________________________________ Note 1. DCP (digestible crude protein): 18% TDN (total amount of digestible nutrients): 68% Note 2. The same crude products as used in examples 11-17 was used.
EXAMPLE 19
Ten Holstein bullocks weighing about 450 kg were divided into two groups (test group and control group) respectively consisting of five Holstein bullocks and the feeding trials were carried out for four weeks by feeding (free feeding) respectively the concentrate feeds with the respective composition described under to the groups. The results were as follows: two bullocks of the control group showed intermitten excessive distensions of their abdomens, namely, the two bullocks were affected with a slight bloat; all the bullocks of the test group did not show bloat at all.
______________________________________Compositions of given concentrate feeds (parts by weight) Agent for bloat-prevention Basic feed or -treatment of the (Note 1) present invention (Note 2)______________________________________Test 100 0.5groupControl 100 0group______________________________________ Note 1. DCP (digestible crude protein): 9.3% TDN (total amount of digestible nutrients): 76% Note 2. The same crude products as used in examples 11-18 was used.
EXAMPLE 20
Twenty five g of the same crude products as used in examples 11-19 was diluted with water and the resulted 1/10 crude products solution was compulsorily administered perorally into one bullock (Holstein bullock weighing about 500 kg, fed by the system feeding much concentrate feed) being ill from a chronic serious bloat and the change with the passage of time in relation to his girth was examined. The results are shown below. One hour after the administration, a thorough vanishment of the distension of his abdomen showed the return of healthy state.
______________________________________Time after the administration Girth(hour) (cm)______________________________________0 2600.5 2411.0 230______________________________________
EXAMPLE 21
Fifty g of the same crude products as used in examples 11-20 was diluted with water and the resulted 1/10 crude products solution was compulsorily administered perorally into one bullock (Japanese indegenous black-haired bullock, the weight: about 500 kg) being ill from a chronic serious bloat and the change with the passage of time in relation to his girth was examined. The results clearly showed the treating effect on the bloat as follows:
______________________________________Time after the administration Girth(hour) (cm)______________________________________0 2351.0 217______________________________________
EXAMPLE 22
The test was carried out as follows: Into one Japanese indegenous brown-haired bullock (the weight: about 650 kg) equipped with a fistula was fed the feed (1) (the same bloat-inducing feed as used in examples 15-17, comprising 61% barley, 22% alfalfa meal, 16% soybean cake and 1% NaCl) at the rate of 8 kg/day for two weeks and thereafter consequtively fed the feed (2) (the feed prepared by adding the same crude products as used in examples 11-21 into the feed (1) in an amount of 1%) at the rate of 8 kg/day as in the case of the feed (1). The rumen juice was collected 4, 8, 11 and 14 days after the start of each feeding during the feedings of the feeds (1) and (2) to measure viscosities and Stable IVIs. The observations were also done. The results were shown in Table 4. The results showed that mixture of the present invention has a preventive effect on bloat.
TABLE 4__________________________________________________________________________State of the rumen juice (Note 1)Viscosity (cp) Before the After the Stable Feeding filtration filtration IVIFeed given period (Note 2) (Note 3) (%) Observation__________________________________________________________________________Feed (1) 2 weeks 12.1 6.2 6.0 The fistula was(only the bloat- separated threeinducing feed) times owing to the rise in the internal pressure of the rumen, during the feeding period.Feed (2) " 7.8 3.9 0 No abnormality(the bloat-inducingfeed + the crudeproducts of thepresent invention(%))__________________________________________________________________________ Note 1. The average value of four times (4, 8, 11 and 14 days after) Note 2. The measurements were carried out before the filtration with double gauzes. Note 3. The measurements were carried out after the elimination of the admixtures with double gauzes.
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An agent for bloat-prevention or -treatment which is useful for preventing or treating bloat caused by feeding large quantities of legume pasture or concentrate feed to ruminants comprises a mixture of a saccharide fatty acid ester and fatty acid salt.
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BACKGROUND OF THE INVENTION
The adjustable tracked side-delivery hay rake according to the present invention is an agricultural machine that is to be employed on the fields for collecting the hay in tidy haycoks.
DESCRIPTION OF THE RELATED ART
It is well known that the existing machines have—all or in part—the following features: they have an adjustable width for the passage on the field, they have an adjustable angle of convergence of the side-delivery hay rake wheels; the weight of said wheels is balanced and sprung; the hay rake wheels are movable between two positions: onelowered on the floor for working, one raised from the floor for transport; finally, the wheels are movable between two further positions, sometimes combined with the preceding ones: a large one for working and a narrow one, less encumbrant and suited for transport.
Furthermore, it is known that above mentioned mobility of the wheels of the hay rake and of the relative arms supporting the wheels from a working position to a transport position are sometimes obtained in such machines known to the art, by performing a rotation of each of the ams supporting the wheels around its own axis placed according to the most different directions according to the machine model. All this means that a certain realization complexity is a common feature of nearly all the machines known, as well as a certain uneasiness in manoeuvring and a relatively high realization cost.
SUMMARY OF THE INVENTION
All said inconveniences and functional negativities may be overcome by means of the adjustable tracked side-delivery rack according to the present invention.
Infact, the side-delivery rack according to the present invention is based—for the movements for adjusting the convergence of said wheels as well as for the movement of the relative arms for supporting the wheels between a large and low position for working and a bent and raised position for transport—on the presence—on the arms supporting the wheels of the machine—of universal joints which allow movements in all directions, the realization of pliable side-delivery racks having an easy and comfortable operation as well as being easy in realization and cheap in the realization cost.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will be described more in detail hereinbelow relating to the enclosed figures, in which:
FIG. 1 , is a rear axonometric view of a scheme of a possible realization of a preferred embodiment of the side-delivery rack according to the present invention, in working position;
FIG. 2 , shows an axonometric front view of the same machine in transport position;
FIG. 3 shows an exploded rear view of the central part of said machine.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Relating now to the details, the figures show:
a pulling steer 2 and the transversal element 3 provided with a plurality of holes 4 and with a plurality of holes 5 ; the right wheels 11 of the side-delivery rack, shown for exemplifying and not limiting purposes in the number of four; the right arm 12 supporting the wheel, consisting of an inner part 13 and of an outer part 14 , and said wheels 11 being applied in rotating manner to said outer part 14 , and arrow 101 showing the raising direction of said right wheels 11 ; the left wings 15 of said side-delivery rack, shown for exemplifying and not limiting purposes in the number of four; the left arm 16 supporting the wheel consisting of an inner part 17 and of an outer part 18 , and said wheels 15 being applied in rotating manner to said outer part 18 , and an arrow 102 showing the raising direction of said left wheels 15 ; the lower right support 21 , sliding with respect to the transversal element 3 in the direction of the arrows 22 and 23 , provided with a plurality of holes 25 , with a plurality of holes 26 , with the couple of holes 27 , with the notch 87 and with the supporting wheel 28 , shown for exemplifying and not limiting purposes in the number of one; the lower left support 31 , sliding with respect to the transversal element 3 in the direction of arrows 32 and 33 , provided with the plurality of holes 35 , with the plurality of holes 36 , with the couple of holes 37 , with the notch 88 and with the supporting wheel 38 , shown for exemplifying and not limiting purposes in the number of one; the orientable right head 41 having the shape of a hollow, lengthened bushing, to which an appendix 42 is applied provided with an end 43 and to which the inner part 13 of the right arm 12 supporting the wheel is hinged in a rotable manner by means of a pin 44 and suspended in elastic manner by means of a spring 45 , and which is provided with holes 46 ; the orientable left head 51 having the shape of a hollow, lengthened bushing, to which an appendix 52 is applied provided with an end 53 and to which the inner part 17 of the left arm 16 supporting the wheel is hinged in a rotable manner by means of a pin 54 and suspended in elastic manner by means of a spring 55 , and which is provided with holes 56 ; the right intermediate element 61 , formed by a bushing 62 to which a first lever 64 is applied provided with an end 65 ; by a pin 66 that may be inserted into said bushing 62 and into holes 27 , thus connecting the right intermediate element 61 to the lower right support 21 in a rotable manner according to arrows 103 and 104 , according to a first rotation axis 6 coinciding with the axis of a pin 66 ; as well as by a pin 63 , preferably but not necessarily fixed in a perpendicular way to said bushing 62 , and that may be inserted into the orientable right head 41 , thus connecting said orientable right head 41 to the right intermediate element 61 in a rotable manner according to arrows 107 and 108 , according to a second rotation axis 7 coinciding with the axis of said pin 63 ; the left intermediate element 71 , formed by a bushing 72 to which a second lever 74 is applied provided with an end 75 ; by a pin 76 that may be inserted into a bushing 72 and into holes 37 , thus connecting the left intermediate element 71 to the lower left support 31 in a rotable manner according to arrows 105 and 106 , according to a third rotation axis 8 coinciding with the axis of a pin 76 ; as well as by a pin 73 , preferably but not necessarily fixed in a perpendicular way to said bushing 72 , and that may be inserted into the orientable left head 51 , thus connecting said orientable left head 51 to the left intermediate element 71 in a rotable manner according to arrows 109 and 110 , according to a fourth rotation axis 9 coinciding with the axis of said pin 73 ; a hydraulic cylinder 81 with double effect and its stem 82 , as said stem 82 is axially extensible and retractile with respect to said hydraulic cylinder 81 with double effect under the action of the same, whereby the end 83 of said stem 82 , the end 84 of said cylinder 81 and a pin 85 are connecting said end 83 of said stem 82 in rotable manner to said end 65 of said first lever 64 , and a pin 86 connecting in rotable manner said end 84 of said cylinder 81 to said end 75 of said second lever 74 ; a right ratchet 91 hinged in rotable manner through a hole 92 onto said pin 85 , and provided with an end 93 to be engaged in said notch 87 , and also provided with a hole 94 , and an arrow 95 showing the raising direction of said right ratchet 91 ; a left ratchet 96 hinged in rotable manner through a hole 97 onto said pin 86 , and provided with an end 98 to be engaged in said notch 88 , and also provided with a hole 99 , and an arrow 100 showing the raising direction of said right ratchet 96 ; strings 131 and 132 that may be knotted respectively to holes 94 and 99 for raising ratchets 91 and 96 in the direction of arrows 95 and 100 ; the right connecting rod 111 provided with a first end 112 , in turn provided with a hole 113 that may be inserted from an end 43 of an appendix 42 wit the result of rotably connecting said end 112 of said connecting rod with said appendix 42 , and provided with a second end 114 with a hole 115 ; the left connecting rod 121 provided with a first end 122 , in turn provided with a hole 123 that may be inserted from an end 53 of an appendix 52 wit the result of rotably connecting said end 122 of said connecting rod with said appendix 52 , and provided with a second end 124 with a hole 125 ; a demountable pin 29 that may be inserted into said holes 4 and 25 ; a demountable pin 39 that may be inserted into said holes 5 and 35 ; a demountable pin 116 that may be inserted into a hole 115 and into holes 26 , with the result of rotably connecting the end 114 of said connecting rod 111 with the lower right support 21 ; a demountable pin 126 that may be inserted into a hole 125 and into holes 36 , with the result of rotably connecting the end 124 of said connecting rod 121 with the lower right support 31 ; a demountable pin 47 that may be inserted into holes 46 ; a demountable pin 57 that may be inserted into holes 56 ;
whereby all said demountable pins are shown in exemplifying and not limiting manner and are of the well known and largely used kind consisting of a rod provided with a swelling on one end and with a transversal hole on the other end, and of a spring plug that may be inserted into said transversal hole.
The hydraulic circuits for operating the hydraulic cylinder 81 with double effect, which are always present in these kinds of machines and of which many kinds are useful for this kind of purpose, are not shown in the figures because they are not relevant for the aim of the present invention.
Relating now to the details shown in the enclosed figures, the working of the machine according to the present invention may be described as follows:
FIG. 1 shows the machine according to the present invention in working position, the wheels open and down.
The angular position of the wheels of the hay rake and of the left and right wheel-supporting arms, are blocked by the constant presence of connecting rods 111 and 121 , which contrast any possible rotation according to arrows 107 or 108 of the right rotary head 41 , and according to arrows 109 or 110 of the left rotary head 51 , as well as of the other parts of the machine according to the present invention connected thereto.
It is possible to vary said angular position by temporarily unstringing the demountable pin 116 from holes 115 and 26 , and the demountable pin 126 from holes 125 and 36 , thus temporarily releasing the connecting rods 111 and 121 ; now the wheels of the hay rake and the arms supporting the wheels may be moved into the new, desired position, blocking them anew and inserting again said demountable pins into holes 115 and 26 and in the holes 125 and 36 , choosing the most suitable ones.
The width of the passage on the field depends on the position of the right lower support 21 and on the position of the left lower support 31 onto the transversal element 3 , and is blocked by the constant presence of the demountable pin 29 inserted in holes 4 and 25 and of the demountable pin 39 inserted in holes 5 and 35 .
It is possible to vary said passage width by temporarily unstringing the demountable pin 29 from holes 4 and 25 and the demountable pin 39 from holes 5 and 35 , thus temporarily releasing the right lower support 21 and the left lower support 31 . Now said elements may be moved into the new desired positions, blocking them anew and inserting again said demountable pins into holes 4 and 25 and into holes 5 and 35 , choosing the most suitable ones. The moving into the two directions of the lower right support 21 and left support 31 may be performed advantageously operating in one sense or in another the double effect hydraulic cylinder 81 , which thus will move in one sense or into the other all parts of the machine connected to end 83 of the stem 82 , and to the end 84 of said cylinder 81 .
The weights of the wheels and of the arms supporting the wheels are balanced and sprung due to the presence of springs 45 and 55 and due to the fact that the inner part of the right arm 13 supporting the wheels and the inner part of the left arm 17 supporting the wheels are respectively hinged onto the right rotary head 41 and onto the left rotary head 51 ; such springing may be eliminated and at the same time the movements of the inner part of the right arm 13 supporting the wheels and of the inner part of the left arm 17 supporting the wheels may be blocked with respect to the right rotary head 41 and to the left rotary head 51 , by introducing a demountable pin 47 into holes 46 and a demountable pin 57 into holes 56 , which may be useful for preventing undesired movements of shaking of the arms supporting the wheels of the hay rake during the transport operations.
The raising and bending of the wheels and of the arms supporting the right as well as the left wheels, with a passage from the working position to the transport position, is performed by shortening the double effect hydraulic cylinder 81 ; as a consequence, the end 84 of said cylinder 81 and the end 83 of the stem 82 pull the end 65 of the first lever 64 and the end 75 of the second lever 74 , which make rotate inwardly the bushing 62 with the pin 63 as well as the bushing 72 with the pin 73 , thus moving also the right rotary head 41 and the left rotary head 51 , with all the parts of the machine according to the present invention connected thereto.
The presence of connecting rods 111 and 121 prevents undesired movements of above mentioned parts of the machine: as it imposes a precise position to end 43 of appendix 42 and to end 53 of appendix 52 , they force all the parts of the machine connected thereto to get placed in the final transport position shown in FIG. 2 .
FIG. 2 shows the side-delivery hay rake according to the present invention in the transport position, the wheels closed and raised.
In said position, the right ratchet 91 , under the action of its own weight, automatically places its own end 93 into the notch 87 of the right lower support 2 , and the left ratchet 96 , under the action of its own weight, automatically places its own weight 98 into the notch 88 of the left lower support 31 .
All this prevents translation movements of said notches and therewith any movement of end 65 of the first lever 64 and of end 75 of the second lever 74 , maintaining also automatically blocked any other movement of all other parts connected with the machine according to the present invention.
For bringing the machine according to the present invention back to its working position, it is necessary first to release said notches raising them in the direction of arrows 95 and 100 by pulling the strings 131 and 132 respectively knotted to holes 94 and 99 ; at this point, the operation in the sense of an elongation of the double effect hydraulic cylinder 81 will bring the wheels and the arms supporting the wheels back downwards and in the working position, causing effects different from those described above.
It is obvious that the operations described above may be performed contemporarily on the right and left wheels and arms supporting the wheels of the hay rake, as well as only on the right or on the left parts; so it will be possible to contemporarily use all the wheels of the machine according to the present invention, or just those of one part thereof.
The great advantage of the machine according to the present invention consists in that the existing connections between the right rotary head 41 and the right lower support 21 , as well as between the left rotary head 51 and the left support 31 , obtained due to the right intermediate element 61 and the left intermediate element 71 —due to the kind of working of said intermediate elements based onto contemporary movements around two rotation axis' being preferably but not necessarily perpendicular one to the other—mainly form the universal joints, i.e. joints that allow movements in all directions.
This fact, together with the presence of connecting rods 111 and 121 , which allow to limit in a simple and precise manner the unlimited movement possibilities of the universal joints, to the sole desired movements, confers to the side-delivery hay rake according to the present invention not only a great flexibility in operating and regulation, but also in projecting and building, which means that it is easy to realize with a great flexibility of models and versions, so as to satisfy the most different requests and needs.
If desired, the connecting rods 111 and 121 may be provided with further devices—of which may exist and are suitable for the purpose—like e.g. screws, threading and similar which allow the regulation in length; the demountable pins 47 and 57 for blocking the springing movement of arms 12 and 16 , may be replaced with any one of the many devices known suitable for the purposes like locks, bolts and similar, without therefore leaving the limits of the present invention.
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An adjustable tracked side-delivery hay rake for use in agriculture for collecting the hay in tidy haycoks, is provided with adjustable wheels movable between a raised and narrow position, suitable for transport and based on the presence—on the arms supporting the wheels—of universal joints that allow movements in all directions.
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TECHNICAL FIELD
[0001] Provided herein is a short-term myocardial infarction based test for identifying a compound, substance or drug that reduces the risk of myocardial infarction in a test subject(s). Further provided is a method for preventing or treating myocardial infarction using the compound, substance or drug identified.
BACKGROUND
[0002] Many new drugs are currently in development which are intended to prevent myocardial infarctions. In addition, it is important to determine whether other investigational drugs could potentially cause myocardial infarctions in recipients as an unintended side effect.
[0003] Current clinical trial protocols for investigational drugs are lengthy, involve a large number of participants, and are extremely expensive. Specifically, these tests take many years, involve thousands of participants, and may cost millions of dollars to complete.
[0004] Accordingly, there is a need for a short-term clinical trial protocol which enables identification, in a shorter time frame and at a lesser cost, of candidate drugs which are designed to prevent myocardial infarctions. There is also a need for a clinical trial designed to determine the risk of drugs for causing myocardial infarctions in subjects, e.g., over a short time period.
SUMMARY
[0005] The present invention relates to a method of designing a short-term myocardial infarction-based test (e.g., clinical trial) in order to demonstrate if a test compound reduces or increases the risk of myocardial infarctions in a test subject. The methods of the present invention can also detect, in a short time frame, whether a candidate drug has a significant risk of causing myocardial infarction in a test subject.
[0006] Trials designed according to the methods of the present invention are advantageous in comparison to traditional Phase III clinical trials for several reasons. First, the trials of the invention are designed to involve fewer participants than standard clinical trials (for example, less than 500 participants). The trials of the invention are also comparatively inexpensive (due to the short time-frame needed to complete the study and the need for fewer participants). They also protect controls from myocardial infarctions, and, importantly, they provide short-term myocardial infarction-based results regarding whether the investigational drug can reduce the risk of myocardial infarction. It is anticipated that additional, long-term clinical trials will still be needed to test for other drug-induced problems, such as side effects and safety considerations.
[0007] In one aspect of the invention, a trial designed according to the invention comprises a modification and improvement of known studies of percutaneous coronary interventions (PCI) and acute coronary syndromes (ACS/infarctions). Prior studies show that the acute treatment of PCI and ACS/infarctions by statins can significantly reduce the incidence of periprocedural myocardial infarctions (PCI) and significantly reduce short-term mortality (ACS/infarctions).
[0008] The method may comprise:
[0009] (a) administering the investigative drug and optionally a statin to a test group of subjects, wherein the test group comprises subjects who are undergoing elective PCI or have ACS/acute myocardial infarction;
[0010] (b) administering a statin to a control group of subjects, wherein the test group has been administered an investigative drug and statin or administering a placebo to a control group of subject wherein the test group has been administered an investigative drug alone, wherein the control group comprises subjects who are undergoing elective PCI or have ACS/acute infarction;
[0011] (c) comparing the subsequent incidences of myocardial infarctions in the subjects who had PCI in the test group with those had PCI in the control group, and
[0012] (d) comparing the subsequent incidences of short-term mortality and/or status of myocardial infarctions in the subjects who had ACS/acute infarction in the test group with that of those who had ACS/acute infarction in the control group;
[0013] wherein if there are significantly less incidences of myocardial infarctions in the subjects who had PCI as compared to those in the control group and/or significantly less incidences of short-term mortality and/or improved status of myocardial infarction in the subjects who had ACS/acute myocardial infarction in the test group as compared to those in the control group, then the investigative drug is capable of preventing myocardial infarctions and
[0014] wherein if there are significantly more incidences of myocardial infarctions in the subjects who had PCI as compared to those in the control group and/or significantly more incidences of short-term mortality in the subjects who had ACS/acute myocardial infarction and/or if status of myocardial infarction has deteriorated in the test group as compared to those in the control group, then the investigative drug increases the risk of a myocardial infarction.
[0015] Thus, in one aspect of the invention, a study or test group comprised of individuals who will be undergoing PCI in the near term (e.g., elective PCI), or are suffering from ACS/infarction (referred to as participants) are administered an investigative drug and optionally a statin. A control group is administered a statin alone, which represents the currently accepted course of therapy or alternatively a placebo when the test group has only been administered the investigative drug alone. If the combination of the statin and the investigative drug is significantly more effective than the statin alone (as administered in the control group) in preventing myocardial infarction and/or acute mortality and/or improving the status of myocardial infarction, the investigative drug is determined to be capable of reducing the risk of myocardial infarction. In another embodiment, if an investigative drug is significantly more effective than the placebo (as administered in the control group) in preventing myocardial infarction and/or acute mortality and/or improving the status of myocardial infarction in a test subject, the investigative drug is determined to be capable of reducing the risk of myocardial infarction. As will be described infra, status of myocardial infarction may be determined by measuring the level of cardiac enzymes in test and control subjects. If significantly more myocardial infarctions occur in the test group, and/or if status of myocardial infarction in a test subject has deteriorated, it is likely that the investigative drug increases the risk of myocardial infarction. The results of clinical trials designed according to the invention are available in the short-term since the participants (those undergoing PCI or having ACS/infarction) are at acute risk for a myocardial infarction or acute mortality. For example, and not by way of limitation, individual results are available in about one, two, or three days for subjects who have undergone PCI and for an individual study of ACS/infarction, results are available in about one, two, or three weeks. In one embodiment, the invention provides relatively prompt overall results, e.g., in six months or less, with multiple study centers.
[0016] The present invention is also directed to methods of reducing the risk of myocardial infarction using a drug identified by the methods disclosed herein and optionally in combination with another substance used to reduce the risk of myocardial infarction.
[0017] The present invention is also directed to a method for modulating and/or treating myocardial infarction using a drug identified by the methods disclosed herein and optionally in combination with another substance used to modulate and/or treat myocardial infarction by administering an amount of the identified drug and optionally other substance effective to modulate and/or treat myocardial infarction. In a particular embodiment, the method may comprise:
(a) identifying a drug capable of modulating and/or treating infarctions and ischemic heart disease comprising:
(i) administering an investigative drug and optionally a statin to a test group of subjects, wherein the test group comprises subjects who are undergoing elective PCI or have ACS/acute myocardial infarction; (ii) administering a statin to a control group of subjects, wherein the test group has been administered an investigative drug and statin or administering a placebo to a control group of subject wherein the test group has been administered an investigative drug alone, wherein the control group comprises subjects who are undergoing elective PCI or have ACS/acute infarction; (iii) comparing the subsequent incidences of myocardial infarctions in the subjects who had PCI in the test group with those had PCI in the control group, and (iv) comparing the subsequent incidences of short-term mortality and/or status of myocardial infarction in the subjects who had ACS/acute infarction with that of those who had ACS/acute infarction in the control group;
wherein if there are significantly less incidences of myocardial infarctions in the subjects who had PCI in the test group as compared to those in the control group and/or significantly less incidences of short-term mortality and/or improved status of myocardial infarctions in the subjects who had ACS/acute myocardial infarction in the test group as compared to those in the control group, then the investigative drug is capable of preventing myocardial infarctions.
(b) administering said identified drug in an amount effective to modulating and/or treating infarctions and ischemic heart disease.
DEFINITIONS
[0024] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either both of those included limits are also included in the invention.
[0025] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the preferred methods and materials are now described.
[0026] It must be noted that as used herein and in the appended claims, the singular forms “a,” “and” and “the” include plural references unless the context clearly dictates otherwise.
[0027] As defined herein, the term “modulate” means adjusting the frequency and/or severity of myocardial infarction.
[0028] As defined herein, the terms “treat”, “treatment” and “treating” are to be understood accordingly as embracing prophylaxis and treatment or amelioration of symptoms of disease as well as treatment of the cause of the disease.
[0029] “Percutaneous coronary interventions (PCI),” commonly known as coronary angioplasty or simply angioplasty, is typically used in two clinical situations. Firstly, elective PCI is used to reduce coronary stenoses (narrowed coronary arteries of the heart) by using balloon dilation. Secondly, it is used for the acute treatment of those with ACS/infarction. Here the goal is to remove thromboses, and also to reduce coronary stenoses to allow more blood flow.
[0030] “Acute coronary syndrome (ACS)” refers to a spectrum of clinical presentations ranging from those for ST-segment elevation myocardial infarction (STEMI) to presentations found in non-ST-segment elevation myocardial infarction (NSTEMI) or in unstable angina. In terms of pathology, ACS is almost always associated with rupture of an atherosclerotic plaque and partial or complete thrombosis of the infarct-related artery. In some instances, however, stable coronary artery disease (CAD) may result in ACS in the absence of plaque rupture and thrombosis, for example, when physiologic stress (e.g., trauma, blood loss, anemia, infection, tachyarrhythmia) increases demands on the heart. The diagnosis of acute myocardial infarction in this setting requires a finding of the typical rise and fall of biochemical markers of myocardial necrosis in addition to at least one of the following: ischemic symptoms: development of pathologic Q waves, or ischemic ST-segment changes on electrocardiogram (ECG) or in the setting of a coronary intervention.
[0031] A “statin” is a member of a broad class of compounds that inhibit the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Examples of statins that may be used in connection with the subject methods include, but are not limited to, lovastatin; simvastatin; pravastatin sodium; fluvastatin sodium; atorvastatin; rosuvastatin; and pitatvastatin.
DETAILED DESCRIPTION
[0032] The present invention is based on the discovery of a short-term myocardial infarction-based test (clinical trial) which is designed to demonstrate if a test compound, e.g., a CETP inhibitor, PCSK9 agent or other investigational drug, reduces the risk of myocardial infarction in a test subject.
[0033] CETP inhibitors are members of a class of drugs that inhibit cholesteryl ester transfer protein (CETP). They are intended to reduce the risk of atherosclerosis by improving blood lipid levels. Cholesteryl ester transfer protein normally transfers cholesterol from high density lipoprotein (HDL) cholesterol to very low density or low density lipoproteins (VLDL or LDL). Inhibition of this process results in higher HDL levels (the so-called “good” cholesterol-containing particle) and reduces LDL levels (the so-called “bad” cholesterol). Examples of CETP inhibitors currently under development include anacetrapib (Merck) and evacetrapib (Eli Lilly & Company). The development of torcetrapib (Pfizer), another CETP inhibitor, was halted in 2006 when phase III studies showed excessive all-cause mortality in the treatment group receiving a combination of atorvastatin (Lipitor) and torcetrapib.
[0034] A “PCSK9 agent” is an agent that modulates the expression and/or synthesis of PCSK9 (proprotein convertase subtilisin kexin 9). PCSK9 is a member of the subtilisin serine protease family that is involved with regulation of hepatic LDL receptor activity. PCSK9 agents may include but are not limited to the PCSK9 monoclonal antibodies, peptide mimics and anti-sense oligonucleotides. PCSK9 agents have been developed to prevent myocardial infarctions by lowering low-density lipoprotein (LDL) cholesterol. These agents generally are planned to be used to supplement statins. PCSK9, a secreted protease, is involved with regulation of hepatic LDL receptor activity. 41,42 Blocking PCSK9 binding to the LDL receptor with a monoclonal antibody lowers LDL cholesterol in humans. 41,42
[0035] Trials designed according to the present invention also detect if investigational or candidate drugs increase the risk of myocardial infarction in a test subject. The present invention is also directed to methods of reducing the risk of myocardial infarctions using a drug identified by the trials designed according to the methods disclosed herein. The participants used in the trials designed according to the methods of the present invention include subjects who will be undergoing elective percutaneous coronary interventions (PCI) or are suffering from acute coronary syndromes (ACS/infarctions). The standard treatment of elective PCI and ACS/infarction by administering a statin is incorporated into the invention. The test group is given a statin plus the experimental drug, and the control group is given only a statin. Alternatively, the test group may be given the experimental drug and the control group is given only a placebo. In a particular embodiment, the test group and control group may be about the same size.
[0036] As described in more detail below, it has been estimated that approximately 40-50% of individuals who have undergone PCI have a mild myocardial infarction. 1,2 The accepted course of treatment during and after PCI involves administration of statins, which prevents about half of these myocardial infarctions. Therefore, it would be expected that approximately 25% of these patients will still experience a myocardial infarction, even when given a statin, in the days following the initial episode. With ACS/myocardial infarction, there is a significant short-term mortality.
[0037] The invention described herein describes a clinical trial wherein patients who will undergo elective PCI, or have ACS/infarction and are in need of therapy, would be given the experimental drug in addition to the normally administered statin (the test group). A control group is administered statin alone.
[0038] The results (e.g., the ability of the test compound to inhibit myocardial infarctions in the PCI group and inhibit mortality in the ACS/infarction group) are available in the short-term since the participants (those having undergone PCI or had ACS/infarction) are at acute risk for a myocardial infarction or acute mortality. For example, individual results are available in about one, two, or three days for subjects who have undergone PCI. For an individual study of ACS/infarction, results are available in about one, two or three weeks. In one embodiment, the invention provides relatively prompt overall results, e.g., in six months or less, with multiple study centers. Likewise, an increase of myocardial infarctions caused by the administration of the experimental drug is also apparent in the short-term.
Basis for the Short-Term Myocardial Infarction-Based Test of the Invention
[0039] The invention is based on the principles that statins and the investigative drug operate additively and acutely by one basic mechanism. Therefore, without being bound by any particular theory, it is useful to list these specific principles, as follows:
1. Risk Factors Directly Induce Myocardial Infarction by Expression of Thrombosis/Vasoconstriction
[0040] It seems apparent that risk factors directly induce myocardial infarction by expression of thrombosis/vasoconstriction; after all, thrombosis is the accepted, 3 and spasm is a proposed, 4 mechanism for the direct induction of myocardial infarction. There is clear evidence that multiple and diverse risk factors for ischemic hear disease (IHD) (pharmaceutical and lifestyle) express as thrombosis/vasoconstriction. 5 Risk factors favor thrombosis/vasoconstriction through endothelial dysfunction and a separate tendency toward thrombosis such as platelet activation and/or sympathetic activation. 5 Myocardial infarctions associated with COX-2 inhibitors provide a specific example of the direct induction of myocardial infarction by risk factor-induced thrombosis/vasoconstriction and are generally attributed directly to thromboxane—which expresses thrombosis/vasoconstriction. 6 This evidence is of particular importance to the short-term test of the invention, as it is based on a drug.
2. Thrombosis or Vasoconstriction and Anti-Thrombosis or Vasodilation
[0041] For the purpose of the short-term myocardial infarction-based test, no opinion is taken about whether thromboses or vasoconstriction directly induce myocardial infarctions—or whether anti-thrombosis or vasodilation directly prevents myocardial infarctions. The distinction is not relevant to this invention. Thrombosis/vasoconstriction (and anti-thrombosis/vasodilation) tends to occur together as a unit 5 —and thromboses is the accepted, 3 and spasm a proposed, 4 mechanism for myocardial infarction.
3. Preventative Factors, Pharmaceutical and Lifestyle, Prevent Myocardial Infarctions Through Expression of Anti-Thrombosis/Vasodilation
[0042] There is clear evidence that multiple and diverse pharmaceutical and lifestyle preventative factors for IHD express anti-thromboses/vasodilation 5 —as part of pleiotrophic effects. If thromboses/vasoconstriction causes myocardial infarctions, reasonably, anti-thrombosis/vasodilation prevents myocardial infarctions.
[0043] Importantly, it generally is accepted that aspirin prevents myocardial infarctions through anti-thrombosis 7 —which reflects the standard paradigm that myocardial infarctions are due directly to thromboses. Aspirin inhibits platelets, which express thrombosis/vasoconstriction. 7
[0044] There is inferential evidence that statins prevent myocardial infarctions through anti-thrombosis/vasodilatory effects. Endothelial dysfunction favors thrombosis/vasoconstriction, 5,8,9 and statins improve endothelial dysfunction. 10-14 Statins also depress the thrombotic arm of thrombosis/vasoconstriction. 15,16 Further, statins suppress COX-2 inhibitors 17 —which express thrombosis/vasoconstriction. 7,18
[0045] Other pharmaceutical preventative agents for IHD improve thrombosis/vasoconstriction. Significantly, aspirin 19 and angiotensin-converting enzyme inhibition 20 also improve endothelial dysfunction. In general, multiple pharmaceutical and lifestyle preventative factors express pleiotrophic effects, which expresses anti-thrombosis/vasodilation. 5
4. Risk Factors Act Acutely to Induce Myocardial Infarction (Through Thrombosis/Vasoconstriction)
[0046] There is evidence that risk factors act acutely to induce myocardial infarction. Significantly, 82.2% of myocardial infarctions in one series acutely followed “triggering” risk factors as acute stress, a heavy meal, and “Monday.” 21 This is interpreted as evidence that multiple risk factors (which express thrombosis/vasoconstriction) can act acutely. Also significant, mental stress induced transient endothelial dysfunction (which favors thrombosis/vasoconstriction) in thirty minutes. 22
5. Preventative Agents can Prevent Myocardial Infarctions Promptly (Supposedly Through Anti-Thrombosis/Vasodilation)
[0047] There is convincing evidence that acute statin therapy promptly reduces the incidence of periprocedural myocardial infarctions after percutaneous coronary interventions (PCI), and reduces the incidence of short-term mortality with acute coronary syndromes (ACS/infarction). The multiple studies of PCI and ACS treated with acute statin therapy show very impressive results—usually around or better than a 50% improvement.
[0048] Individual studies of PCI showed a significant reduction of periprocedural myonecrosis with statins over controls by 3.7% vs. 9.4%, 23 9.5% vs. 15.8%, 24 and 5% vs. 18%. 1 Also, the incidence of large non-Q-wave myocardial infarction was 8% in the statin group and 15.6% in the control group. 25
[0049] Meta-analyses of statin treatment with PCI showed similar results. There was a reduction of periprocedural myonecrosis over controls of 9.0% vs. 17.5% 2 and 7.7% vs. 14.2%. 26 Another large study showed a 43% reduction of post-procedural myocardial infarctions. 27
[0050] Studies of acute statin use with ACS/infarction showed reduction of in-hospital mortality and morbidity as compared to controls by 4.0-5.3% vs. 15.45 28 and 5% vs. 17%. 29
[0051] Meta-analyses of statin use with ACS/infarctions showed a reduction of deaths at 7 days (0.4% vs. 2.6%) 30 and 30 days (0.5% vs. 1.0%). 31
[0052] Finally, acute statin therapy with PCI in cases of ACS showed a lower rate of periprocedural myocardial injury over controls (5.8% vs. 11.4%). 32
[0053] There is evidence that statins act acutely to prevent myocardial infarctions through anti-thrombosis/vasodilatory effects; statins improved endothelial dysfunction (which favors thrombosis/vasoconstriction) when measured at 60 minutes, 10 24 hours, 11 10 days, 12 2 weeks, 13 and 4 weeks. 14 Also, anti-platelet effects (anti-thrombosis/vasodilation) of aspirin are measurable by 60 minutes. 7
[0054] Further, angiotensin-converting inhibition improved endothelial dysfunction when measured at 4 weeks. 20 Another study 33 showed that angiotensin converting enzyme inhibition prompted parasympathetic activation (which improves endothelial dysfunction 5 ) when measured at 30 days. While measured at a month's time, it seems reasonable that actual benefits occurred significantly earlier.
[0055] The lability of endothelial function can be used as evidence that preventative substances tend to act promptly to improve endothelial dysfunction. This lability is demonstrated by several parameters: The ability of mental stress to induce transient endothelial dysfunction by 30 minutes, 22 the ability of statins to promptly improve endothelial dysfunction, and the very beneficial effects of acute statin therapy with PCI and ACS/infarction. In this light, it is likely that angiotensin-converting enzyme inhibition improved endothelial dysfunction much more promptly than 4 weeks. It also is likely that other pharmaceutical agents that prevent myocardial infarction and improve endothelial function act acutely.
6. Risk Factors Act Additively
[0056] There is general agreement that risk factors act additively. 3,34
7. Preventative Pharmaceutical Agents Operate Additively
[0057] That preventative agents act additively is commonly accepted. 3 As example, the combination of statins, angiotensin converting inhibitors, and aspirin reduced the risk of death in IHD by 71%. 35
8. Summary
[0058] Again, without wishing to be bound by any particular theory, the above evidence supports the tenet that preventative pharmaceutical agents operate acutely and additively, most likely by pleiotrophic anti-thrombosis/vasodilation. Therefore, the short-term myocardial infarction-based test for investigative drugs is based on sound principles. If the combination of a preventative measure (especially a statin) plus an investigative drug act significantly more beneficially than a preventative measure (e.g., a statin), this is evidence that the investigative drug reduces the risk of myocardial infarction.
[0059] A second rationale can be used: as the preventative agent (as a statin) is given to both the test and control groups, the preventative agent cancels out. Therefore, the test evaluates the ability of the investigative drug to act more beneficially than the control group.
Methods of Designing Clinical Trials of the Invention
[0060] In one aspect of the present invention, individuals who are undergoing elective PCI or are experiencing ACS/acute myocardial infarction are separated into two groups, the test group and the control group. In a particular embodiment, the test group and the control group may be about the same size. The test group is given a statin plus the investigative drug, and the control group is given the usual statin (e.g., at about the same dose as the test group). In a particular embodiment, statin therapy is given according to standard protocols for the treatment of elective PCI and ACS/acute myocardial infarction.
[0061] Generally, the investigative drug is given at the same time as the statin. Alternatively, as set forth above, the test group is given the investigative drug and the control group is given a placebo.
[0062] If there is a statistically significant lower incidence of myocardial infarction (for the subjects who are undergoing elective PCI) and short-term mortality (for the subjects with ACS/acute myocardial infarction) in the test group, this is prima facie evidence that the investigative drug reduces the risk of myocardial infarctions when used in the usual clinical setting. Preferentially, statistically significant results should include about a 10% or more reduction of infarctions between about one day to about seven days after undergoing the elective PCI and/or about a 10% or more reduction in mortality rate between about two weeks to about one month, two months, three months, four months, five months or six months after undergoing the elective PCI. However, if the test group has a pronounced higher incidence of myocardial infarctions or mortality, it is likely that the drug causes myocardial infarctions. By giving all test group participants a statin, including the control group, all cases are treated as any individuals undergoing elective PCI or treatment of ACS/acute myocardial infarction would be treated under the current standard of care. Because of the administration of the statin, both the test group and the control group are protected against myocardial infarction. As both the test and control groups are given about the same dose of a statin, in some embodiments, effects of the statin are balanced out, leaving only the effect of the experimental drug on PCI and ACS/infarction.
[0063] The design of the clinical trials of the invention provide relatively prompt results as compared to accepted clinical trials of investigational drugs. In one embodiment, results of individual cases should be available, for example, in about one day, two, three, four, five, or six days, or a week for those who had elective PCI (measuring post-procedural myocardial infarctions), and within about a week, two weeks, three weeks, or a month, for those who had ACS/infarctions (measuring short-term mortality).
[0064] Also, because myocardial infarctions are highly concentrated, relatively small numbers of test subjects are necessary, e.g., about 50, 100, 200, 300, 400 or 500 test subjects, for the methods of the invention. For individuals who have suffered from ACS/infarction, about 100% of cases have myocardial infarctions. With PCI, incidence of periprocedural myocardial infarctions up to 40-50% have been reported. 1,2 However, studies of PCI reported above showed incidences of periprocedural myocardial infarctions in controls between 9.4%, 23 15.6%, 25 15.7%, 24 and 18%. 1 Therefore, smaller numbers of cases are needed with ACS/infarction than with PCI to achieve statistical significance. However, total number of combined controls and test cases for PCI have been rather small (153, 1 668, 24 383, 23 and 451 25 ).
[0065] Periprocedural myocardial infarctions generally are mild and only detected by elevation of cardiac enzymes. 1,24 However, these mild infarctions are treated conventionally as genuine mild infarctions. In keeping with this, the incidence of large non-Q-wave infarction after PCI was 8% in the statin group and 15.6% in the control group 25 —findings similar to studies of periprocedural myonecrosis after PCI.
[0066] However, to solidify that the short-term myocardial infarction-based test directly predicts results of standard long-term phase III tests, it is helpful to use both PCI and ACS models. The former model is based on preventing myocardial infarctions, and the latter model is based on reducing the impact of an acute ACS/infarction.
[0067] In some embodiments, dosage of statins for the short-term myocardial infarction-based test of the invention follows common practices with statin treatment of elective PCI and with ACS/infarction. The patient, in a specific embodiment, may be administered low (10-20 mg), moderate (20-40 mg) or high doses (40-80 mg) of statin. For example, 80 23,24 and 40 1 mg per day of atorvastatin has been used with elective PCI and can be used in the methods of the invention, although use of moderate doses of other statins is not excluded. For example, in an alternative embodiment, a “high” dose of 40 mg, “moderate” dose of 20 mg, “low” dose of 10 mg and “very low” dose of 5 mg of rosuvastatin may be used. Also, in one embodiment, the statin therapy can be done in combination with one or more other effective preventative agents, such as angiotensin-converting enzyme inhibitors. Also, use of preventative drugs other than statins are also included in some embodiments.
[0068] Although there is evidence that the acute effects of statins are manifested quickly in favoring anti-thrombosis/vasodilation, in one embodiment, there can be a period of pretreatment, for example to ensure full activation of the investigative drug. Pretreatment with statins (and the investigative drug) for elective PCI can be, for example, 12 hours to 31 days or more in advance. For example, pretreatment times of statins for PCI have ranged from around 12 hours 23 to 31 days, 2 and most times have been about 7 days or more. 1,2,24 Common practices for advance administration of the statin can be used in the methods of the invention.
[0069] The investigative drug can also be administered in advance of PCI. If there is concern that the investigative drug will take longer than statins to develop its full therapeutic effect, the dosing of the investigative drug for elective PCI can begin significantly longer than a week prior to PCI. For ACS, to account for a possible tardy full effect of the investigative drug, evaluation of short-term mortality can be extended past 4 weeks, for example to 6 weeks or 8 weeks.
[0070] Doses of an investigative drug can be employed as used in other trials of the investigative drug or as determined by pre-clinical trials or determined based on dose of other like drugs. In general, investigative drugs can be used at high dosage, but moderate doses are not excluded.
[0071] Differences of incidences of periprocedural infarctions (PCI) and short-term mortality (ACS/infarction) between the test and control group are determined, using appropriate statistical methodology as is known in the art.
[0072] Incidences of periprocedural myocardial infarctions with PCI is determined in test and control groups by standard methods for determining the occurrence of myocardial infarction. 36 In one embodiment, biomarker evaluation of myocardial infarction can be used. 36,37 The preferred biomarker for myocardial necrosis is cardiac troponin (I or T). 36,37 With PCI, in one embodiment, measurement of cardiac enzymes is performed before or immediately after the procedure, and again at 6-12 and 18-24 hours. 36
[0073] For ACS/infarction, in one embodiment, evaluation of the status of the myocardial infarction in test and control cases (especially by cardiac enzymes) is performed at admission, several times during the hospital stay, and when the protocol ends the trial, for example, at one week, one month, or six weeks. In particular, status of myocardial infarction may be determined to be improved in test subjects if there is a statistically significant reduction in cardiac enzymes in test subjects as compared to controls.
CETP Inhibitors
[0074] Current investigative cholesteryl ester transfer protein (CETP) inhibitor drugs (for example, anacetrapib (Merck) and evacetrapib (Eli Lilly & Company)) and other similar drugs are especially propitious drugs for testing by the short-term myocardial infarction-based test of the invention. The proposed uses of these drugs simulates the short-term myocardial infarction-based test.
[0075] These drugs, which elevate high density lipoprotein (HDL) cholestero 1 , 38-39 are generally planned to be used to supplement drugs (as statins) which lower low density lipoprotein (LDL) cholesterol.
[0076] Trials of experimental CETP inhibitors used the following doses: anacetraapib 100 mg/day 38 and evacetrapib 30, 100, and 500 mg/day. 40
PCSK9 Agents
[0077] PCSK9 agents have been developed to prevent myocardial infarctions by lowering low-density lipoprotein (LDL) cholesterol. These agents may be used to supplement statins but could be used alone as well. PCSK9, a secreted protease, is involved with regulation of hepatic LDL receptor activity 41,42
[0078] Blocking PCSK9 binding to the LDL receptor with a monoclonal antibody has been found to lower LDL cholesterol in humans. 41,42 The PCSK9 monoclonal antibody AMG 145 (Amgen) has been injected subcutaneously every four weeks at 350 mg. and 420 mg. 41,42 as well as subcutaneously every 2 weeks at 70 mg., 105 mg., and 140 mg. Also, the monoclonal antibody REGN727/SAR236553 (Regeneron/Sanofi) was injected subcutaneously every 4 weeks at doses of 200 or 300 mg., or 150 mg every two weeks. 41,42
Advantages of the PCI and ACS/Myocardial Infarction Models
[0079] There are advantages to both the PCI and the ACS/acute infarction models. Elective PCI allows premedication. Also, periprocedural infarctions after PCI generally are mild, 1,24 thus limiting the risk of the study. Post PCI myocardial infarctions generally are asymptomatic, 1 and generally are defined as a three fold elevation of creatine kinase-myocardial isoenzyme. 24 Also, if, as expected, the investigative drug reduces the risk of myocardial infarctions, this will aid half the cases (the test group).
[0080] The ACS/acute myocardial infarction model has a special advantage, as myocardial infarctions are serious and can result in significant short-term mortality. If the investigative drug reduces the risk of myocardial infarctions, the drug will give more protection against short-term mortality to half the cases (the test group).
[0081] An important issue is the ability of the investigative drug to fare well with the test. That is, to prevent myocardial infarctions with individuals undergoing PCI, and lower short-term mortality with individuals suffering from ACS. Importantly, the short-term myocardial infarction-based test of the invention simulates two separate clinical situations: the direct prevention of myocardial infarctions (with individuals undergoing PCI) and limiting the acute term mortality of myocardial infarctions (with individuals suffering from ACS/infarctions).
[0082] If an investigative drug is effective in these situations, the drug will likely prevent infarctions in the clinical situation in high risk individuals in a clinical setting.
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[0125] This invention may be embodied in other forms or carried out in other ways without departing from the spirit or essential characteristics thereof. The present disclosure is therefore to be considered as in all aspects illustrate and not restrictive, and all changes which come within the meaning and range of equivalency are intended to be embraced therein.
[0126] Various publications are cited herein, the contents of which are hereby incorporated by reference in their entireties.
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Provided herein is a short-term myocardial infarction based test for identifying a compound, substance or drug that reduces the risk of myocardial infarction and optionally ischemic heart disease in a test subject(s). Further provided is a method for preventing or treating myocardial infarction using the compound, substance or drug identified.
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FIELD OF THE INVENTION
[0001] The present invention relates to imido and amido substituted acylhydroxamic acids, the method of reducing levels or activities of cytokines such as tumor necrosis factor α in a mammal through the administration thereof, and pharmaceutical compositions of such derivatives.
BACKGROUND OF THE INVENTION
[0002] Tumor necrosis factor-α (TNFα) is a cytokine which is released primarily by cells of immune systems in response to certain immunostimulators. When administered to animals or humans, it causes inflammation, fever, cardiovascular effects, hemorrhage, coagulation, cachexia, and acute phase responses similar to those seen during acute infections, inflammatory diseases, and shock states. Excessive or unregulated TNFα production has been implicated in a number of disease conditions. These include endotoxemia and/or toxic shock syndrome [Tracey, et al., Nature 330, 662-664 (1987) and Hinshaw, et al., Circ. Shock 30, 279-292 (1990)], rheumatoid arthritis, inflammatory bowel disease, cachexia [Dezube, et al., Lancet, 335 (8690), 662 (1990)], and lupus. TNFα concentration in excess of 12,000 pg/mL have been detected in pulmonary aspirates from Adult Respiratory Distress Syndrome (ARDS) patients [Millar, et al., Lancet 2(8665), 712-714 (1989)]. Systemic infusion of recombinant TNFα resulted in changes typically seen in ARDS [Ferrai-Baliviera, et al., Arch. Surg. 124(12), 1400-1405 (1989)].
[0003] TNFα appears to be involved in a number of bone resorption diseases, including arthritis. When activated, leukocytes will produce bone-resorption. TNFα apparently contributes to this mechanism. [Bertolini, et al., Nature 319, 516-518 (1986) and Johnson, et al., Endocrinology 124(3), 1424-1427 (1989)]. TNFα also has been shown to stimulate bone resorption and inhibit bone formation in vitro and in vivo through stimulation of osteoclast formation and activation combined with inhibition of osteoblast functions. Another compelling link with disease is the association between production of TNFα by tumor or host tissues and malignancy associated hyper-calcemia [ Calci. Tissue Int. ( US ) 46(Suppl.), S3-10 (1990)]. In Graft versus Host Reactions, increased serum TNFα levels have been associated with major complication following acute allogenic bone marrow transplants [Holler, et al., Blood, 75(4), 1011-1016 (1990)].
[0004] Validation of TNF-α inhibition as a clinical therapy has been demonstrated by the therapeutic use of TNF-α antibodies and soluble TNF-α receptors. TNFα blockage with monoclonal anti-TNFα antibodies has been shown to be beneficial in rheumatoid arthritis [Elliot, et al., Int. J. Pharmac. 1995 17(2), 141-145]. High levels of TNFα are associated with Crohn's disease [von Dullemen, et al., Gastroenterology, 1995 109(1), 129-135] treatment with soluble TNFα receptor treatment gave clinical benefits.
[0005] Cerebral malaria is a lethal hyperacute neurological syndrome associated with high blood levels of TNFα and the most severe complication occurring in malaria patients. Elevated levels of serum TNFα correlated directly with the severity of disease and the prognosis in patients with acute malaria attacks [Grau, et al., N. Engl. J. Med. 320(24),1586-1591 (1989)).
[0006] TNFα plays a role in the area of chronic pulmonary inflammatory diseases. The deposition of silica particles leads to silicosis, a disease of progressive respiratory failure caused by a fibrotic reaction. Antibodies to TNFα completely blocked the silica-induced lung fibrosis in mice [Pignet, et al., Nature, 344, 245-247 (1990)]. High levels of TNFα production (in the serum and in isolated macrophages) have been demonstrated in animal models of silica and asbestos induced fibrosis [Bissonnette, et al., Inflammation 13(3), 329-339 (1989)]. Alveolar macrophages from pulmonary sarcoidosis patients have also been found to spontaneously release massive quantities of TNFα as compared with macrophages from normal donors [Baughman, et al., J. Lab. Clin. Med. 115(1), 36-42 (1990)].
[0007] Elevated levels of TNFα are implicated in reperfusion injury, the inflammatory response which follows reperfusion, and is a major cause of tissue damage after blood flow loss [Vedder, et al., PNAS 87, 2643-2646 (1990)]. TNFα also alters the properties of endothelial cells and has various pro-coagulant activities, such as producing an increase in tissue factor pro-coagulant activity, suppressing the anticoagulant protein C pathway, and down-regulating the expression of throm-bomodulin [Sherry, et al., J. Cell Biol. 107, 1269-1277 (1988)]. TNFα has pro-inflammatory activities which together with its early production (during the initial stage of an inflammatory event) make it a likely mediator of tissue injury in several important disorders including but not limited to, myocardial infarction, stroke and circulatory shock. TNFα-induced expression of adhesion molecules, such as intercellular adhesion molecules (ICAM) or endothelial leukocyte adhesion molecules (ELAM) on endothelial cells may be especially important [Munro, et al., Am. J. Path. 135(1), 121-132 (1989)].
[0008] It has been reported that TNFα is a potent activator of retrovirus replication including activation of HIV-1. [Duh, et al., Proc. Nat. Acad. Sci. 86, 5974-5978 (1989); Poll, et al., Proc. Nat. Acad. Sci. 87, 782-785 (1990); Monto, et al., Blood 79, 2670 (1990); Clouse, et al., J. Immunol. 142, 431-438 (1989); Poll, et al., AIDS Res. Hum. Retrovirus, 191-197 (1992)). At least three types or strains of HIV (i.e., HIV-1, HIV-2 and HIV-3) have been identified. As a consequence of HIV infection, T-cell mediated immunity is impaired and infected individuals manifest severe opportunistic infections and/or unusual neoplasms. HIV entry into the T-lymphocyte requires T-lymphocyte activation. Other viruses, such as HIV-1, HIV-2 infect T-lymphocytes after T-cell activation. This virus protein expression and/or replication is mediated or maintained by this T-cell activation. Once an activated T-lymphocyte is infected with HIV, the T-lymphocyte must continue to be maintained in an activated state to permit HIV gene expression and/or HIV replication. Cytokines, specifically TNFα, are implicated in activated T-cell mediated HIV protein expression and/or virus replication by playing a role in maintaining T-lymphocyte activation. Therefore, interference with cytokine activity such as prevention or inhibition of cytokine production, notably TNFα, in an HIV-infected individual assists in limiting the maintenance of T-lymphocyte caused by HIV infection.
[0009] Monocytes, macrophages, and related cells, such as kupffer and glial cells, also have been implicated in maintenance of the HIV infection. These cells, like T-cells, are targets for viral replication and the level of viral replication is dependent upon the activation state of the cells. (Rosenberg, et al., The Immunopathogenesis of HIV Infection, Advances in Immunology, 57 (1989)]. Cytokines, such as TNFα, have been shown to activate HIV replication in monocytes and/or macrophages [Poli, et al., Proc. Natl. Acad. Sci., 87, 782-784 (1990)], therefore, prevention or inhibition of cytokine production or activity aids in limiting HIV progression for T cells. Additional studies have identified TNFα as a common factor in the activation of HIV in vitro and has provided a clear mechanism of action via a nuclear regulatory protein found in the cytoplasm of cells [Osborn, et al., PNAS 86 2336-2340]. This evidence suggests that a reduction of TNFα synthesis may have an antiviral effect in HIV infections, by reducing transcription and thus virus production.
[0010] AIDS viral replication of latent HIV in T cell and macrophage lines can be induced by TNFα [Folks, et al., PNAS 86, 2365-2368 (1989)]. A molecular mechanism for the virus inducing activity is suggested by TNFα's ability to activate a gene regulatory protein (NFκB) found in the cytoplasm of cells, which promotes HIV replication through binding to a viral regulatory gene sequence (LTR) [Osborn, et al., PNAS 86, 2336-2340 (1989)]. TNFα in AIDS associated cachexia is suggested by elevated serum TNFα and high levels of spontaneous TNFα production in peripheral blood monocytes from patients [Wright, et al., J. Immunol. 141(1), 99-104 (1988)]. TNFα has been implicated in various roles with other viral infections, such as the cytomegalia virus (CMV), influenza virus, adenovirus, and the herpes family of viruses for similar reasons as those noted.
[0011] The nuclear factor κB (NFκB) is a pleiotropic transcriptional activator (Lenardo, et al., Cell 1989, 58, 227-29). NFκB has been implicated as a transcriptional activator in a variety of disease and inflammatory states and is thought to regulate cytokine levels including but not limited to TNFα and active HIV transcription [Dbaibo, et al., J. Biol. Chem. 1993, 17762-66; Duh, et al., Proc. Natl. Acad. Sci. 1989, 86, 5974-78; Bachelerie, et al., Nature 1991, 350, 709-12; Boswas, et al., J. Acquired Immune Deficiency Syndrome 1993, 6, 778-786; Suzuki, et al., Biochem. And Biophys. Res. Comm. 1993, 193, 277-83; Suzuki, et al., Biochem. And Biophys. Res Comm. 1992, 189, 1709-15; Suzuki, et al., Biochem. Mol. Bio. Int. 1993, 31(4), 693-700; Shakhov, et al., Proc. Natl. Acad. Sci. USA 1990, 171, 35-47; and Staal, et al., Proc. Natl. Acad. Sci. USA 1990, 87, 9943-47]. Thus, it would be helpful to inhibit NFκB activation, nuclear translation or binding to regulate transcription of cytokine gene(s) and through this modulation and other mechanisms be useful to inhibit a multitude of disease states.
[0012] Many cellular functions are mediated by levels of adenosine 3′,5′-cyclic monophosphate (cAMP). Such cellular functions can contribute to inflammatory conditions and diseases including asthma, inflammation, and other conditions (Lowe and Cheng, Drugs of the Future, 17(9), 799-807, 1992). It has been shown that the elevation of cAMP in inflammatory leukocytes inhibits their activation and the subsequent release of inflammatory mediators, including TNFα and NFκB. Increased levels of cAMP also lead to the relaxation of airway smooth muscle.
[0013] The primary cellular mechanism for the inactivation of cAMP is the breakdown of cAMP by a family of isoenzymes referred to as cyclic nucleotide phosphodiesterases (PDE) [Beavo and Reitsnyder, Trends in Pharm., 11, 150-155, 1990]. There are ten known members of the family of PDEs. It is well documented that the inhibition of PDE type IV (PDE 4) enzyme is particularly effective in both the inhibition of inflammatory mediator release and the relaxation of airway smooth muscle [Verghese, et al., Journal of Pharmacology and Experimental Therapeutics, 272(3), 1313-1320,1995].
[0014] Decreasing TNFα levels and/or increasing cAMP levels thus constitutes a valuable therapeutic strategy for the treatment of many inflammatory, infectious, immunological, and malignant diseases. These include but are not restricted to: septic shock, sepsis, endotoxic shock, hemodynamic shock and sepsis syndrome, post ischemic reperfusion injury, malaria, mycobacterial infection, meningitis, psoriasis and other dermal diseases, congestive heart failure, fibrotic disease, cachexia, graft rejection, cancer, tumor growth, undesirable angiogenesis, autoimmune disease, opportunistic infections in AIDS, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, other arthritic conditions, inflammatory bowel disease, Crohn's disease, ulcerative colitis, multiple sclerosis, systemic lupus erythrematosis, ENL in leprosy, radiation damage, and hyperoxic alveolar injury. Prior efforts directed to the suppression of the effects of TNFα have ranged from the utilization of steroids such as dexamethasone and prednisolone to the use of both polyclonal and monoclonal antibodies [Beutler, et al., Science 234, 470-474 (1985); WO 92/11383].
[0015] Angiogenesis, the process of new blood vessel development and formation, plays an important role in numerous normal and pathological physiological events. Angiogenesis occurs in response to specific signals and involves a complex process characterized by infiltration of the basal lamina by vascular endothelial cells in response to angiogenic growth signal(s), migration of the endothelial cells toward the source of the signal(s), and subsequent proliferation and formation of the capillary tube. Blood flow through the newly formed capillary is initiated after the endothelial cells come into contact and connect with a preexisting capillary. Angiogenesis is required for tumor growth beyond a certain size.
[0016] Inhibitory influences predominate in the naturally occurring balance between endogenous stimulators and inhibitors of angiogenesis [Rastinejad, et al., 1989, Cell 56:345-355]. In those rare instances in which neovascularization occurs under normal physiological conditions, such as wound healing, organ regeneration, embryonic development, and female reproductive processes, angiogenesis is stringently regulated and spatially and temporally delimited. Under conditions of pathological angiogenesis such as that characterizing solid tumor growth, these regulatory controls fail.
[0017] Unregulated angiogenesis becomes pathologic and sustains progression of many neoplastic and non-neoplastic diseases. A number of serious diseases are dominated by abnormal neovascularization including solid tumor growth and metastases, arthritis, some types of eye disorders, and psoriasis [Moses, et al., 1991, Biotech. 9:630-634; Folkman, et al., 1995, N. Engl. J. Med., 333:1757-1763; Auerbach, et al., 1985, J. Microvasc. Res. 29:401-411; Folkman, 1985, Advances in Cancer Research, eds. Klein and Weinhouse, Academic Press, New York, pp. 175-203; Patz, 1982, Am. J. Opthalmol. 94:715-743; and Folkman, et al., 1983, Science 221:719-725]. In a number of pathological conditions, the process of angiogenesis contributes to the disease state. For example, significant data suggests that the growth of solid tumors is dependent on angiogenesis [Folkman and Klagsbrun, 1987, Science 235:442-447].
[0018] The maintenance of the avascularity of the cornea, lens, and trabecular meshwork is crucial for vision as well as for ocular physiology. See, e.g., reviews by Waltman, et al., 1978, Am. J. Ophthal. 85:704-710 and Gartner, et al., 1978, Surv. Ophthal. 22:291-312. Currently, the treatment of these diseases, especially once neovascularization has occurred, is inadequate and blindness often results.
[0019] An inhibitor of angiogenesis could have an important therapeutic role in limiting the contributions of this process to pathological progression of the underlying disease states as well as providing a valuable means of studying their etiology. For example, agents that inhibit tumor neovascularization could play an important role in inhibiting metastatic and solid tumor growth.
[0020] Several kinds of compounds have been used to prevent angiogenesis. Taylor, et al. used protamine to inhibit angiogenesis, [Taylor, et al., Nature 297:307 (1982)). The toxicity of protamine limits its practical use as a therapeutic. Folkman, et al. used heparin and steroids to control angiogenesis. [Folkman, et al., Science 221:719 (1983) and U.S. Pat. Nos. 5,001,116 and 4,994,443]. Steroids, such as tetrahydrocortisol, which lack gluco and mineral corticoid activity, are angiogenic inhibitors. Interferon β is also a potent inhibitor of angiogenesis induced by allogeneic spleen cells [Sidky, et al., Cancer Research 47:5155-5161 (1987)]. Human recombinant interferon-α was reported to be successfully used in the treatment of pulmonary hemangiomatosis, an angiogenesis-induced disease [White, et al., New England J. Med. 320:1197-1200 (1989)].
[0021] Other agents which have been used to inhibit angiogenesis include ascorbic acid ethers and related compounds [Japanese Kokai Tokkyo Koho No. 58-131978]. Sulfated polysaccharide DS 4152 also shows angiogenic inhibition [Japanese Kokai Tokkyo Koho No. 63-119500]. A fungal product, fumagillin, is a potent angiostatic agent in vitro. The compound is toxic in vivo, but a synthetic derivative, AGM 12470, has been used in vivo to treat collagen II arthritis. Fumagillin and o-substituted fumagillin derivatives are disclosed in EPO Publication Nos. 0325199A2 and 0357061A1.
[0022] In U.S. Pat. No. 5,874,081, Parish teaches use of monoclonal antibodies to inhibit angiogenesis. In WO92/12717, Brem, et al. teach that some tetracyclines, particularly Minocycline, Chlortetracycline, Demeclocycline and Lymecycline are useful as inhibitors of angiogenesis. Brem, et al. teach that Minocycline inhibits angiogenesis to an extent comparable to that of the combination therapy of heparin and cortisone [ Cancer Research, 51, 672-675, Jan. 15, 1991). Teicher, et al. teach that tumor growth is decreased and the number of metastases is reduced when the anti-angiogenic agent of metastases is reduced when the anti-angiogenic agent Minocycline is used in conjunction with cancer chemotherapy or radiation therapy [ Cancer Research, 52, 6702-6704, Dec. 1, 1992].
[0023] Macrophage-induced angiogenesis is known to be stimulated by TNFα. Leibovich, et al. reported that TNFα induces in vivo capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membranes at very low doses and suggested TNFα is a candidate for inducing angiogenesis in inflammation, wound repair, and tumor growth [ Nature, 329, 630-632 (1987)].
[0024] All of the various cell types of the body can be transformed into benign or malignant tumor cells. The most frequent tumor site is lung, followed by colorectal, breast, prostate, bladder, pancreas, and then ovary. Other prevalent types of cancer include leukemia, central nervous system cancers, brain cancer, melanoma, lymphoma, erythroleukemia, uterine cancer, bone cancer, and head and neck cancer.
[0025] Cancer is now primarily treated with one or a combination of three types of therapies: surgery, radiation, and chemotherapy. Surgery involves the bulk removal of diseased tissue. While surgery is sometimes effective in removing tumors located at certain sites (e.g., in the breast, colon, and skin) surgery cannot be used in the treatment of tumors located in other areas (e.g., the backbone) nor in the treatment of disseminated neoplastic conditions (e.g., leukemia). Chemotherapy involves the disruption of cell replication or cell metabolism. Chemotherapy is used most often in the treatment of leukemia, as well as breast, lung, and testicular cancer.
[0026] Chemotherapeutic agents are often referred to as antineoplastic agents. The alkylating agents are believed to act by alkylating and cross-linking guanine and possibly other bases in DNA, arresting cell division. Typical alkylating agents include nitrogen mustards, ethyleneimine compounds, alkyl sulfates, cisplatin, and various nitrosoureas. A disadvantage with these compounds is that they not only attack malignant cells, but also other cells which are naturally dividing, such as those of bone marrow, skin, gastro-intestinal mucosa, and fetal tissue. Antimetabolites are typically reversible or irreversible enzyme inhibitors, or compounds that otherwise interfere with the replication, translation or transcription of nucleic acids. Thus, it would be preferable to find less toxic compounds for cancer treatment.
[0027] Matrix metalloproteinase (MMP) inhibition has been associated with several activities including inhibition of TNFα [Mohler, et al., Nature, 370, 218-220 (1994)] and inhibition of angiogenesis. MMPs are a family of secreted and membrane-bound zinc endopeptidases that play a key role in both physiological and pathological tissue degradation [Yu, et al., Drugs & Aging, 1997, (3):229-244; Wojtowicz-Praga, et al., Int. New Drugs, 16:61-75 (1997)]. These enzymes are capable of degrading the components of the extracellular matrix, including fibrillar and non-fibrillar collagens, fibronectin, laminin, and membrane glycoproteins. Ordinarily, there is a delicate balance between cell division, matrix synthesis, matrix degradation (under the control of cytokines), growth factors, and cell matrix interactions. Under pathological conditions, however, this balance can be disrupted. Conditions and diseases associated with undesired MMP levels include, but are not limited to: tumor metastasis invasion and growth, angiogenesis, rheumatoid arthritis, osteoarthritis, osteopenias such as osteoporosis, periodontitis, gingivitis, Crohn's disease, inflammatory bowel disease, and corneal epidermal or gastric ulceration.
[0028] Increased MMP activity has been detected in a wide range of cancers [Denis, et al., Invest. New Drugs, 15: 175-185 (1987)]. As with TNFα, MMPs are believed to be involved in the invasive processes of angiogenesis and tumor metastasis.
DETAILED DESCRIPTION
[0029] The present invention is based on the discovery that certain classes of compounds more fully described herein decrease the levels of TNFα, increase cAMP levels, inhibit phosphodiesterases (PDEs, in particular PDE 4), affect tumors, and affect angiogenesis.
[0030] The compounds described herein can inhibit the action of NFκB in the nucleus and thus are useful in the treatment of a variety of diseases including but not limited to rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, other arthritic conditions, septic shock, sepsis, endotoxic shock, graft versus host disease, wasting, inflammatory bowel disease, Crohn's disease, ulcerative colitis, multiple sclerosis, systemic lupus erythrematosis, ENL in leprosy, cancer, HIV, AIDS, and opportunistic infections in AIDS. TNFα and NFκB levels are influenced by a reciprocal feedback loop. As noted above, the compounds of the present invention affect the levels of both TNFα and NFκB. Compounds in this application inhibit PDE4.
[0031] In particular, the invention pertains to
[0032] (a) compounds of the formula:
[0033] wherein
[0034] the carbon atom designated * constitutes a center of chirality,
[0035] R 4 is hydrogen or —(C═O)—R 12 ;
[0036] each of R 1 and R 12 , independently of each other, is alkyl of 1 to 6 carbon atoms, phenyl, benzyl, pyridyl methyl, pyridyl, imidazoyl, imidazolyl methyl, or CHR*(CH 2 ) n NR*R 0
[0037] wherein R*and R 0 , independently of the other, are hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, benzyl, pyridylmethyl, pyridyl, imidazoyl or imidazolylmethlyl, and n=0, 1, 2;
[0038] R 5 is C═O, CH 2 , CH 2 —CO—, or SO 2 ;
[0039] each of R 6 and R 7 , independently of the other, is nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, cycloalkoxy of 3 to 8 carbon atoms, halo, bicycloalkyl of up to 18 carbon atoms, tricycloalkoxy of up to 18 carbon atoms, 1-indanyloxy, 2-indanyloxy, C 4 -C 8 -cycloalkylidenemethyl, or C 3 -C 10 -alkylidenemethyl;
[0040] each of R 8 , R 9 , R 10 , and R 11 , independently of the others, is
[0041] (i) hydrogen, nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkylamino, dialkylamino, acylamino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, halo, or
[0042] (ii) one of R 8 , R 9 , R 10 , and R 11 is acylamino comprising a lower alkyl, and the remaining of R 8 , R 9 , R 10 , and R 11 are hydrogen, or
[0043] (iii) hydrogen if R 8 and R 9 taken together are benzo, quinoline, quinoxaline, benzimidazole, benzodioxole, 2-hydroxybenzimidazole, methylenedioxy, dialkoxy, or dialkyl, or
[0044] (iv) hydrogen if R 10 and R 11 , taken together are benzo, quinoline, quinoxaline, benzimidazole, benzodioxole, 2-hydroxybenzimidazole, methylenedioxy, dialkoxy, or dialkyl, or
[0045] (v) hydrogen if R 9 and R 10 taken together are benzo; and
[0046] (b) The acid addition salts of said compounds which contain a nitrogen atom capable of being protonated.
[0047] The carbon atom designated with an * constitutes a center of chirality. Both optical isomers are part of this invention. Unless otherwise defined, the preferred R group of R—(C═O)— in acyl and the acyl of acylamino in this invention is alkyl of 1 to 6 carbon atoms, phenyl, benzyl, pyridylmethyl, pyridyl, imidazoyl, imidazolylmethlyl, or CHR*(CH 2 ) n NR*R 0 , wherein R*and R 0 , independently of the other, are hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, benzyl, pyridylmethyl, pyridyl, imidazoyl or imidazolylmethlyl, and n=0, 1, 2. Alkyl is preferably unbranched. Branched and/or cyclic alkyl forms are also envisioned.
[0048] Subgroups of Formula I can include the following: The acylhydroxamic acid derivative in Formula I, wherein R 4 is hydrogen; R 5 is C═O; R 8 is hydrogen; and one of R 9 and R 11 is hydrogen and the other of R 9 and R 11 , taken together with R 10 , is benzo, methylenedioxy, dioxo, or dialkoxy. The acylhydroxamic acid derivative in Formula I, wherein R 4 is hydrogen; R 5 is C═O; R 8 and R 9 are hydrogen; and R 10 and R 11 , taken together, are methylenedioxy. The acylhydroxamic acid derivative in Formula I, wherein one or more of R 8 , R 9 , R 10 , and R 11 , independently of the others, is hydrogen, alkyl of 1 to 10 carbon atoms, or alkoxy of 1 to 10 carbon atoms. The acylhydroxamic acid derivative in Formula I, wherein R 8 , R 9 , R 10 , and R 11 are (a) at least one alkyl of 1 to 10 carbon atoms (i.e., a lower alkyl) with the remainder of R 8 , R 9 , R 10 , and R 11 being hydrogen, or (b) at least one alkoxy of 1 to 10 carbon atoms with the remainder of R 8 , R 9 , R 10 , and R 11 being hydrogen. For the purposes of this invention, acylamino includes acetamido. The acylhydroxyamic acid derivative in Formula I, which is a substantially chirally pure (3R)-isomer, a substantially chirally pure (3S)-isomer, or a mixture thereof. The acylhydroxamic acid derivative in Formula I, wherein R 4 is hydrogen. The acylhydroxamic acid derivative in Formula I, wherein R 4 is —(C═O)—R 12 . The acylhydroxamic acid derivative in Formula I, wherein each of R 8 , R 9 , R 10 , and R 11 is hydrogen, halo, alkyl of 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms. The acylhydroxamic acid derivative in Formula I, wherein one of R 8 , R 9 , ,R 10 , or R 11 is amino, acylamino, alkylamino, dialkylamino, or hydroxy. An acylhydroxamic acid derivative in Formula I, wherein R 1 is alkyl of 1 to 10 carbon atoms, pyridyl, or imidazolyl.
[0049] Unless otherwise defined, the term alkyl denotes a univalent saturated branched or straight hydrocarbon chain containing from 1 to 10 carbon atoms. Representative of such alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, and tert-butyl. Alkoxy refers to an alkyl group bound to the remainder of the molecule through an ethereal oxygen atom. Representative of such alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, and tert-butoxy. Acetylamino also includes the name acetamido. Methylenedioxy may sometimes be called dioxo.
[0050] In Formula I, each of R 8 , R 9 , R 10 , and R 11 can be hydrogen, halo, alkyl of 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms. Alternatively, one of R 8 , R 9 , R 10 , and R 11 is amino, alkyl amino, dialkyl amino, or acyl amino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, or hydroxy, and the remaining of R 8 , R 9 , R 10 , and R 11 are hydrogen. Formula I, can also have R 8 , R 9 , R 10 , and R 11 as hydrogen. Formula I can be a substantially chirally pure (R)-isomer, a substantially chirally pure (S)-isomer, or a mixture thereof.
[0051] A pharmaceutical composition can contain a quantity of an acylhydroxamic acid derivative of Formula I, which derivative is a substantially chirally pure (R)-isomer, a substantially chirally pure (S)-isomer, or a mixture thereof, sufficient upon administration in a single or multiple dose regimen to reduce or inhibit levels of TNFα or to treat cancer, undesired angiogenesis, or arthritis in a mammal in combination with a carrier. A pharmaceutical composition can contain a quantity of Formula I which is a substantially chirally pure (R)-isomer, a substantially chirally pure (S)-isomer, or a mixture thereof, sufficient upon administration in a single or multiple dose regimen to inhibit undesirable levels of matrix metalloproteinases and/or PDE4 in a mammal in combination with a carrier.
[0052] This invention includes the following methods along with other reasonably expected methods. A method of reducing or inhibiting undesirable levels of TNFα in a mammal which comprises administering thereto an effective amount of an acylhydroxamic acid derivative of Formula I, which derivative is a substantially chirally pure (R)-isomer, a substantially chirally pure (S)-isomer, or a mixture thereof. A method of reducing or inhibiting undesirable levels of matrix metalloproteinases in a mammal which comprises administering thereto an effective amount of an acylhydroxamic acid derivative of Formula I, which derivative is a substantially chirally pure (R)-isomer, a substantially chirally pure (S)-isomer, or a mixture thereof. A method of treating in a mammal a disease selected from the group consisting of but not limited to inflammatory disease, autoimmune disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, aphthous ulcers, cachexia, graft versus host disease, asthma, adult respiratory distress syndrome, and acquired immune deficiency syndrome, which comprises administering thereto an effective amount of a compound described by Formula I, which compound is a substantially chirally pure (R)-isomer, a substantially chirally pure (S)-isomer, or a mixture thereof. A method of treating cancer in a mammal which comprises administering thereto an effective amount of a compound described by Formula I, which compound is a substantially chirally pure (R)-isomer, a substantially chirally pure (S)-isomer, or a mixture thereof. A method of treating undesirable angiogenesis in a mammal which comprises administering thereto an effective amount of a compound described by Formula I, which compound is a substantially chirally pure (R)-isomer, a substantially chirally pure (S)-isomer, or a mixture thereof. Also included in this invention is a method of reducing or inhibiting phosphodiesterases IV (PDE4) in a mammal which comprises administering thereto an effective amount of an acylhydroxamic acid derivative described by Formula I, which derivative is a substantially chirally pure (R)-isomer, a substantially chirally pure (R)-isomer, or a mixture thereof.
[0053] The compounds of Formula I are used, under the supervision of qualified professionals, to inhibit the undesirable effects of TNFα and/or inhibit phosphodiesterases, and/or inhibit inflammation and/or angiogenesis and/or cancer. Inhibition of the phosphodiesterase type 4 (PDE4 or PDE IV) is the preferred embodiment in this application. The compounds can be administered orally, rectally, or parenterally, alone or in combination with other therapeutic agents including antibiotics, steroids, etc., to a mammal in need of treatment.
[0054] The compounds of the present invention also can be used topically in the treatment or prophylaxis of topical disease states mediated or exacerbated by inflammation excessive TNFα production, excessive MMPs, or where increased cAMP levels will be helpful, Some examples include viral infections, such as those caused by the herpes viruses or viral conjunctivitis, or dermal conditions such as psoriasis or atopic dermatitis, etc.
[0055] The compounds can also be used in the veterinary treatment of mammals other than humans in need of prevention or inhibition of TNFα production. TNFα mediated diseases for treatment, therapeutically or prophylactically, in animals include disease states such as those noted above, but in particular viral infections. Examples include feline immunodeficiency virus, equine infectious anaemia virus, caprine arthritis virus, visna virus, and maedi virus, as well as other lentiviruses.
[0056] Angiogenesis, the process of new blood vessel development and formation, plays an important role in numerous physiological events, both normal and pathological. The compounds also can be used to inhibit unwanted angiogenesis. The compounds may also be used to inhibit tumor growth.
[0057] The invention also relates to MMP-inhibiting compounds, compositions thereof, and their use in the treatment of diseases and disorders associated with undesired production or activity of MMPs. These compounds are capable of inhibiting connective tissue breakdown, and are useful in the treatment or prevention of conditions involving tissue breakdown. These include, but are not limited to, tumor metastasis, invasion, and growth, rheumatoid arthritis, osteoarthritis, osteopenias such as osteoporosis, periodontitis, gingivitis, and corneal epidermal inflammatory bowel disease, or gastric ulceration.
[0058] The following Formulas are related as follows. The compounds according to Formula III are the starting material for the compounds of Formula II. The compound of Formula II is the starting material for the compounds of Formula IV in Reaction a to produce the compound of Formula I(b).
[0059] The compounds of Formula IV are readily prepared by reacting a carboxylic acid of the formula:
[0060] with hydroxylamine hydrochloride or an alkoxyamine hydrochloride in the presence of a coupling agent. R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are defined above. The reaction generally is conducted in an inert solvent such as tetrahydrofuran, ethyl acetate, etc. under an inert atmosphere such as nitrogen. Ambient or above ambient temperatures can be employed. When the reaction is substantially complete, generally the products can be readily isolated simply through the addition of water.
[0061] The compounds of Formula II which are here utilized as intermediates are described in U.S. Pat. No. 5,605,914, the disclosure of which is incorporated herein by reference. Briefly, such intermediates can be prepared through the reaction of an amino acid of the formula:
[0062] in which R 14 is hydroxy, alkoxy, or a protecting group, with an anhydride, an N-carbethoxyimide, a dialdehyde, or an o-bromo aromatic acid.
[0063] Protecting groups utilized herein denote groups which generally are not found in the final therapeutic compounds but which are intentionally introduced at some stage of the synthesis in order to protect groups which otherwise might be altered in the course of chemical manipulations. Such protecting groups are removed at a later stage of the synthesis and compounds bearing such protecting groups thus are of importance primarily as chemical intermediates (although some derivatives also exhibit biological activity). Accordingly the precise structure of the protecting group is not critical. Numerous reactions for the formation and removal of such protecting groups are described in a number of standard works including, for example, “Protective Groups in Organic Chemistry”, Plenum Press, London and New York, 1973; Greene, Th. W. “Protective Groups in Organic Synthesis”, Wiley, New York, 1981; “The Peptides”, Vol. I, Schröder and Lubke, Academic Press, London and New York, 1965; “Methoden der organischen Chemie”, Houben-Weyl, 4th Edition, Vol.15/I, Georg Thieme Verlag, Stuttgart 1974, the disclosures of which are incorporated herein by reference.
[0064] In any of the foregoing reactions, a nitro compound can be employed with the nitro group being converted to an amino group by catalytic hydrogenation or chemical reaction. Alternatively, a protected amino group can be deprotected to yield the corresponding amino compound. An amino group can be protected as an amide utilizing an acyl group which is selectively removable under mild conditions, especially benzyloxycarbonyl, formyl, or a lower alkanoyl group, each of which is branched in a 1- or α position to the carbonyl group, particularly tertiary alkanoyl such as pivaloyl, a lower alkanoyl group which is substituted in the position α to the carbonyl group, as for example trifluoroacetyl.
[0065] In a preferred embodiment, hydroxamic acids such as those prepared above can be reacted with acid anhydrides, in acetonitrile (CH 3 CN) or other inert solvent as follows:
[0066] in which Reaction a is a reaction of IV with an anhydride of the formula (R 1 CO) 2 O in CH 3 CN. R 1 , R 4 , R 5 , and R 6 to R 11 are defined above. A mixture of two main reaction products (A) and (B) may result. The first reaction product (A) has R 4 being hydrogen. The second reaction product (B) has R 4 being —(C═O)—R 12 . R 12 is defined above. Reaction products (A) and (B) can be purified by column chromatography. The crude product can also be slurried in hexane several times to afford pure reaction product (A). Reaction product (B), where R 12 is not the same as R 1 , can be prepared from treatment of (A) with an acid anhydride containing the desired R 12 group. Formula I(b) is Formula I or can be a subgroup of Formula I.
[0067] The compounds of Formula I possess at least one center of chirality (designated by “*”) and thus can exist as optical isomers. Both the racemates of these isomers and the individual isomers themselves, as well as diastereomers when there are two chiral centers, are within the scope of the present invention. The racemates can be used as such or can be separated into their individual isomers mechanically as by chromatography using a chiral absorbent. Alternatively, the individual isomers can be prepared in chiral form or separated chemically from a mixture by forming salts with a chiral acid or base, such as the individual enantiomers of 10-camphorsulfonic acid, camphoric acid, α-bromocamphoric acid, methoxyacetic acid, tartaric acid, di-acetyltartaric acid, malic acid, pyrrolidone-5-carboxylic acid, and the like, and then freeing one or both of the resolved bases, optionally repeating the process, so as obtain either or both substantially free of the other; i.e., in a form having an optical purity of >95%. Chiral bases can also be used for this process.
[0068] Formula I(c) is a subgroup of Formula I. Formula 1(c) represents (a) an acylhydroxamic acid derivative having the formula:
[0069] in which
[0070] the carbon atom designated * constitutes a center of chirality,
[0071] R 4 is hydrogen or —(C═O)—R 12 ;
[0072] each of R 1 and R 12 , independently of each other, is alkyl of 1 to 6 carbon atoms, phenyl, benzyl, pyridyl methyl, pyridyl, imidazoyl, imidazolyl methyl, or CHR*(CH 2 ) n NR*R 0
[0073] wherein R*and R 0 , independently of the other, are hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, benzyl, pyridylmethyl, pyridyl, imidazoyl or imidazolylmethlyl, and n=0, 1, 2;
[0074] R 5 is C═O, CH 2 , CH 2 —CO—, or SO 2 ;
[0075] each of R 6 and R 7 , independently of the other, is nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, cycloalkoxy of 3 to 8 carbon atoms, halo, bicycloalkyl of up to 18 carbon atoms, tricycloalkoxy of up to 18 carbon atoms, 1-indanyloxy, 2-indanyloxy, C 4 -C 8 -cycloalkylidenemethyl, or C 3 -C 10 -alkylidehemethyl;
[0076] each of R 8 , R 9 , R 10 , and R 11 , independently of the others, is
[0077] (i) hydrogen, nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkylamino, dialkylamino, acylamino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, halo, or
[0078] (ii) one of R 8 , R 9 , R 10 , and R 11 is acylamino comprising a lower alkyl, and the remaining of R 8 , R 9 , R 10 , and R 11 are hydrogen, or
[0079] (iii) hydrogen if R 8 and R 9 taken together are benzo, quinoline, quinoxaline, benzimidazole, benzodioxole, 2-hydroxybenzimidazole, methylenedioxy, dialkoxy, or dialkyl, or
[0080] (iv) hydrogen if R 10 and R 11 , taken together are benzo, quinoline, quinoxaline, benzimidazole, benzodioxole, 2-hydroxybenzimidazole, methylenedioxy, dialkoxy, or dialkyl, or
[0081] (v) hydrogen if R 9 and R 10 taken together are benzo; and
[0082] (b) The acid addition salts of said compounds which contain a nitrogen atom capable of being protonated.
[0083] The present invention also pertains to the physiologically acceptable non-toxic acid addition salts of the compound of Formula I. Such salts include those derived from organic and inorganic acids such as, without limitation, hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, methanesulphonic acid, acetic acid, tartaric acid, lactic acid, succinic acid, citric acid, malic acid, maleic acid, sorbic acid, aconitic acid, salicylic acid, phthalic acid, embonic acid, enanthic acid, and the like.
[0084] Oral dosage forms include tablets, capsules, dragees, and similar shaped, compressed pharmaceutical forms containing from 1 to 100 mg of drug per unit dosage. Isotonic saline solutions containing from 20 to 100 mg/mL can be used for parenteral administration which includes intramuscular, intrathecal, intravenous and intra-arterial routes of administration. Rectal administration can be effected through the use of suppositories formulated from conventional carriers such as cocoa butter.
[0085] Pharmaceutical compositions thus comprise one or more compounds of Formulas I or the compounds of the product in Reaction a associated with at least one pharmaceutically acceptable carrier, diluent or excipient. In preparing such compositions, the active ingredients are usually mixed with or diluted by an excipient or enclosed within such a carrier which can be in the form of a capsule or sachet. When the excipient serves as a diluent, it may be a solid, semi-solid, or liquid material which acts as a vehicle, carrier, or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, elixirs, suspensions, emulsions, solutions, syrups, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders. Examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidinone, polyvinylpyrrolidone, cellulose, water, syrup, and methyl cellulose, the formulations can additionally include lubricating agents such as talc, magnesium stearate and mineral oil, wetting agents, emulsifying and suspending agents, preserving agents such as methyl- and propylhydroxybenzoates, sweetening agents or flavoring agents.
[0086] The compositions preferably are formulated in unit dosage form, meaning physically discrete units suitable as a unitary dosage, or a predetermine fraction of a unitary dose to be administered in a single or multiple dosage regimen to human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with a suitable pharmaceutical excipient. The compositions can be formulated so as to provide an immediate, sustained or delayed release of active ingredient after administration to the patient by employing procedures well known in the art.
[0087] TNFα inhibition in LPS stimulated human peripheral blood mononuclear cells (PBMCs) can be performed as described below. Enzyme-linked immunosorbent assays (ELISA) for TNFα can be performed in a conventional manner. PBMCs are isolated from normal donors by Ficoll-Hypaque density centrifugation. Cells are cultured in RPMI supplemented with 10% AB+ serum, 2 mM L-glutamine, 100 U/mL (units per milliliter) penicillin, and 100 mg/mL streptomycin. Drugs are dissolved in dimethylsulfoxide (Sigma Chemical) and further dilutions are done in supplemented RPMI (a well known media). The final dimethylsulfoxide concentration in the presence or absence of drug in the PBMC suspensions is 0.25 wt %. Drugs are assayed at half-log or log dilutions starting at 100 μM. Drugs are added to PBMC (10 6 cells/mL) in 96 wells plates one hour before the addition of LPS. PBMCs (10 6 cells/mL) in the presence or absence of drug are stimulated by treatment with 1 μg/mL or 100 ng/mL of LPS from Salmonella minnesota R595 (List Biological Labs, Campbell, Calif.). Cells are then incubated at 37° C. for 18-20 hours. Supernatants are harvested and assayed immediately for TNFα levels or kept frozen at 31 70° C. (for not more than 4 days) until assayed. The concentration of TNFα in the supernatant is determined by human TNFα ELISA kits (ENDOGEN, Boston, Mass.) according to the manufacturer's directions.
[0088] Inhibition of phosphodiesterase type 4 (PDE 4) can also be determined in conventional models. For example, using a modification of the method of Hill and Mitchell, U937 cells (a human promonocytic cell line) are grown to 1×10 6 cells/mL and collected by centrifugation. A cell pellet of 1×10 9 cells is washed in phosphate buffered saline and then frozen at −70° C. for later purification or immediately lysed in cold homogenization buffer (20 mM Tris-HCl, pH 7.1, 3 mM 2-mercaptoethanol, 1 mM magnesium chloride, 0.1 mM ethylene glycol-bis-(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), 1 μM phenylmethylsulfonyl fluoride (PMSF), and 1 μg/mL leupeptin). Cells are homogenized with 20 strokes in a Dounce homogenizer and the supernatant containing the cytosolic fraction are obtained by centrifugation. The supernatant is then loaded onto a Sephacryl. S-200 column equilibrated in homogenization buffer. The crude phosphodiesterase type 4 enzyme is eluted in homogenization buffer at a rate of approximately 0.5 mL/min and fractions are assayed for phosphodiesterase activity using rolipram. Fractions containing PDE 4 activity (rolipram sensitive) are pooled and aliquoted for later use.
[0089] The phosphodiesterase assay is carried out based on the procedure described by Hill and Mitchell [Hill and Mitchell, Faseb J., 8, A217 (1994)]. The assay is carried out in a total volume of 100 μl containing various concentration of the compounds of interest, 50 mM Tris-HCl, pH 7.5, 5 mM magnesium chloride and 1 μM cAMP of which 1% is 3 H cAMP. Reactions are incubated at 30° C. for 30 minutes and then terminated by boiling for 2 minutes. The amount of PDE 4 containing extract used for these experiments is predetermined such that reactions are within the linear range and consume less than 15% of the total substrate. Following termination of reaction, samples are chilled at 4° C. and then treated with 10 μL of 10 mg/mL snake venom for 15 min at 30° C. Unused substrate then is removed by adding 200 μl of a quaternary ammonium ion exchange resin (AG1-X8, BioRad) for 15 minutes. Samples then are spun at 3000 rpm, 5 min and 50 μl of the aqueous phase are taken for counting. Each data point is carried out in duplicate and activity is expressed as percentage of control. The IC 50 s of the compounds are then determined from dose response curves of a minimum of three independent experiments.
[0090] Representative examples include a substantially chirally pure (R)-isomer, a substantially, chirally pure (S)-isomer, or a mixture thereof, where the isomer is (3-(1, 3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate; (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl) propanoylamino) acetate; (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino)-pentanoate; (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoyl-amino) benzoate; (3-(3-cyclopentyloxy-4-methoxy phenyl)-3-(1-oxoisoindolin-2-yl) propanoylamino) acetate; (3-[4-(acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl) propanoylamino) acetate; (3-(3-ethoxy-4-methoxyphenyl)-3-(4-methyl -1,3-dioxoisoindolin-2-yl)propanoyl amino) acetate; (3-(3-ethoxy-4-methoxy-phenyl) -3-(5-methyl-1,3-dioxoisoindolin-2-yl)propanoylamino) acetate; (3-(3-cyclo-pentyloxy -4-methoxyphenyl)-3-(4-methyl-1 ,3-dioxoisoindolin-2-yl)propanoylamino) acetate; (3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl) propanoylamino) acetate; -N-acetyl-3-(3-ethoxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin -2-yl)propanoylamino) acetate; N-acetyl-3-(3-cyclopentyloxy-4-methoxy -phenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl)propanoylamino) acetate; (3-[5-(acetylamino)-1, 3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-ethoxyphenyl)propanoylamino) acetate; (3-(1,3-dioxobenzo[e] isoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl) propanoyl-amino) acetate; (3-(3-ethoxy-4-methoxyphenyl)-3-phthalimido-propanoyl-amino) pyridine-3-carboxylate; (3-[4-(acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-cyclopentyloxy -4-methoxyphenyl)propanoylamino) acetate; (N-acetyl-3-[4-(acetyl-amino) -1,3-dioxoisoindolin-2-yl]-3-(3-cyclopentyloxy-4-methoxyphenyl) propanoyl-amino) acetate; or (3-(3-ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolin-2-yl)propanoyl-amino) acetate. The following examples will serve to further typify the nature of this invention but should not be construed as a limitation in the scope thereof, which scope is defined solely by the appended claims.
EXAMPLE 1
(3-(1 ,3-Dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate
[0091] A mixture of 3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl) propanehydroxamic acid (5.8 g, 15 mmol) and propionic anhydride (3.93 g, 30.2 mmol) in anhydrous acetonitrile (170 mL) was stirred at room temperature under nitrogen overnight. Removal of solvent in vacuo yielded an oil. The oil was then stirred in ether (25 mL). The resulting suspension was filtered and washed with ether to give (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate as a white solid (2.8 g, 42%): mp, 181.0-183.5° C.; 1 H NMR (DMSO-d6) δ 1.01 (t, J=7.5 Hz, 3H, CH 2 CH 3 ), 1.31 (t, J=6.9 Hz, 3H, OCH 2 CH 3 ), 2.39 (q, J=7.4 Hz, 2H, CH 2 ), 3.12-3.35 (m, 2H, CH 2 ), 3.97 (q, J=7.4 Hz, 2H, CH 2 ), 5.67 (t, J=7.7 Hz, 1H, CH), 6.90 (s, 2H, Ar), 7.02 (s, 1H, Ar), 7.83-7.86 (m, 4H, Ar), 11.87 (br, s, 1H, NH); 13 C NMR (DMSO-d6) δ 8.2, 14.1, 23.7, 33.4, 49.3, 54.9, 63.2, 111.3, 111.7, 118.9, 122.6, 130.5, 130.7, 134.6, 147.2, 148.1, 166.1, 167.1, 171.1; Anal. Calcd. For C 23 H 24 N 2 O 7 : C, 62.72; H, 5.49; N, 6.36. Found: C, 62.62; H, 5.50; N, 6.18.
EXAMPLE 2
(3-(1,3-Dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) acetate
[0092] (3-(1,3-Dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) acetate was prepared by the procedure of Example 1 from 3-(1,3-dioxoisoindolin-2-yl) -3-(3-ethoxy-4-methoxyphenyl)propanehydroxamic acid (0.5 g, 1.3 mmol) and acetic anhydride (0.27 g, 2.6 mmol) in anhydrous acetonitrile (20 mL). The product was obtained as a white solid (0.25 g, 45%): mp, 180.0-182.0° C.; 1 H NMR (DMSO-d6) δ 1.31 (t, J=6.7 Hz, 3H, CH 3 ), 2.07 (s, 3H, CH 3 ), 3.10-3.26 (m, 2H, CH 2 ), 3.72 (s, 3H, OCH 3 ), 4.00 (q, J=6.4 Hz, 2H, OCH 2 ), 5.67 (t, J=7.7 Hz, 1H CH), 6.89 (s, 2H, Ar), 7.02 (s, 1H, Ar), 7.82-7.85 (m, 4H, Ar), 11.86 (br s, 1H, NH); 13 C NMR (DMSO-d6) δ 14.6, 17.9, 33.9, 49.8, 55.4, 63.7, 111.8, 112.1, 119.4, 123.1, 130.9, 131.2, 134.5, 147.7, 148.5, 166.5, 167.6, 168.1; Anal. Calcd. For C 22 H 22 N 2 O 7 : C, 61.97; H, 5.20; N, 6.57. Found: C, 62.01; H, 5.26; N, 6.43.
EXAMPLE 3
(3-(1,3-Dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) pentanoate
[0093] (3-(1,3-Dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) pentanoate was prepared as described in Example 1 from 3-(1,3-dioxoisoindolin-2-yl) -3-(3-ethoxy-4-methoxyphenyl)propanehydroxamic acid (1.0 g, 2.6 mmol) and pentanoic anhydride (0.97 g, 5.2 mmol) in anhydrous acetonitrile (30 mL). The product was obtained as a white solid (0.45 g, 37%): mp, 200.0-201.5° C.; 1 H NMR (DMSO-d6) δ 0.83 (t, J=7.3 Hz, 3H, CH 3 ), 1.25-1.33 (m, 2H, CH 2 ), 1.31 (t, J=6.8 Hz, 3H, CH 3 ), 1.33-1.48 (m, 2H, CH 2 ), 2.36 (t, J=7.2 Hz, 2H, CH 3 ), 3.10-3.20 (m, 2H, CH 2 ), 3.72 (s, 3H, CH 3 ), 4.02 (q, J=6.4 Hz, 2H, OCH 2 ), 5.67 (t, J=7.6 Hz, 1H, CH), 6.89-7.01 (m, 3H, Ar), 7.85 (s, 4H, Ar), 11.86 (s, 1H, NH); 13 C NMR (DMSO-d6) δ 13.4, 14.6, 21.3, 26.3, 30.4, 49.7, 55.4, 63.7, 111.8, 112.2, 119.4, 123.1, 130.9, 131.2, 134.5, 147.7, 148.5, 166.6, 167.6, 170.8; Anal. Calcd. for C 25 H 28 N 2 O 7 : C, 64.09; H, 6.02; N, 5.98. Found: C, 63.89; H, 6.04; N, 5.81.
EXAMPLE 4
(3-(1,3-Dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) benzoate
[0094] (3-(1,3-Dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoyiamino) benzoate was prepared as described in Example 1 from 3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanehydroxamic acid (1.0 g, 2.6 mmol) and phenylcarbonyl benzoate (1.18 g, 5.2 mmol) in anhydrous acetonitrile (30 mL). The product was obtained as a white solid (0.70 g, 55.1%): mp, 196.0-198.0° C.; 1 H NMR (DMSO-d6) δ 1.33 (t, J=6.6 Hz, 3H, CH 3 ), 3.31-3.46 (m, 2H, CH 2 ), 3.74 (s, 3H, OCH 3 ), 4.03 (q, J=6.4 Hz, 2H, OCH 2 ), 5.72 (t, J=7.5 Hz, 1H, CH), 6.94-7.07 (m, 3H, Ar), 7.50-8.00 (m, 9H, Ar), 12.20 (s, 1H, NH); 13 C NMR (DMSO-d6) δ 55.5, 63.7, 111.8, 112.2, 119.4, 123.2, 126.6, 129.0, 129.4, 131.0, 131.2, 134.3, 134.6, 147.7, 148.6, 163.8, 167.0, 167.6; Anal. Calcd. for C 27 H 24 N 2 O 7 : C, 65.42; H, 5.10; N, 5.61. Found: C, 65.10; H, 4.90; N, 5.49.
EXAMPLE 5
(3-(3-Cyclopentyloxy-4-methoxyphenyl)-3-(1-oxoisoindolin-2-yl)propanoylamino) acetate
[0095] (3-(3-Cyclopentyloxy-4-methoxyphenyl)-3-(1-oxoisoindolin-2-yl)propanoylamino) acetate was prepared by the general procedure A from 3-(3-cyclopentyloxy-4-methoxyphenyl) -3-(1-oxoisoindolin-2-yl)propanehydroxamic acid (2.86 g, 7.0 mmol) and acetic anhydride (1.42 g, 14.0 mmol) in anhydrous acetonitrile (110 mL). The product was obtained as a white solid (0.79 g, 27%): mp, 166.0-168.5° C.; 1 H NMR (DMSO-d6) δ 1.50-1.82 (m, 8H, C 5 H 8 ), 2.09 (s, 3H, CH 3 ), 3.04 (d, J=7.9 Hz, 2H CH 2 ), 3.71 (s, 3H, OCH 3 ), 4.17 (d, J=17.4 Hz, 1H, CHH),), 4.60 (d, J=17.4 Hz, 1H, CHH), 4.69-4.75 (m, 1H, OCH), 5.67 (t, J=7.8 Hz, 1H, CH), 6.83-6.93 (m, 3H, Ar), 7.45-7.70 (m, 4H, Ar), 11.86 (s, 1H, NH); 13 C NMR (DMSO-d6) δ 17.9, 23.5, 32.1, 34.6, 51.0, 55.5, 79.5, 112.2, 113.9, 119.1, 122.8, 123.4, 127.8, 131.3, 131.6, 132.2, 141.7, 146.9, 149.1, 166.6, 167.0, 168.3; Anal. Calcd. for C 25 H 28 N 2 O 6 : C, 65.06; H, 6.33; N, 6.07. Found: C, 65.3; H, 6.26; N, 5.85.
EXAMPLE 6
(3-[4-(Acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-mathoxyphenyl) propanoylamino) acetate
[0096] (3-[4-(Acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl) propanoylamino) acetate was prepared by the procedure of Example 1 from N-[2-[2-(N -hydroxycarbamoyl)-1-(3-ethoxy-4-methoxyphenyl)ethyl]-1,3-dioxoisoindolin-4-yl]acetamide (0.8 g, 1.8 mmol) and acetic anhydride(0.37 g, 3.6 mmol) in anhydrous acetonitrile (30 mL). The product was isolated as a white solid (0.55 g, 62.8%): mp, 279.0-280.0° C.; 1 H NMR (DMSO-d6) δ 1.31 (t, J=6.9 Hz, 3H, CH 3 ), 2.07 (s, 3H, CH 3 ), 2.19 (s, 3H, CH 3 ), 3.15-3.26 (m, 2H, CH 2 ), 3.72 (s, 3H, OCH 3 ), 3.97 (q, J =6.4 (q, J=6.4 Hz, 2H, OCH 2 ), 5.64 (t, J=7.7 Hz, 1H, CH), 6.90-6.99 (m, 3H, Ar), 7.56 (d, J=7.3 Hz, 1H, Ar), 7.78 (t, J=7.7 Hz, 1H, Ar), 8.45 (d, J=8.0 Hz, 1H, Ar), 9.71 (s, 1H, NH), 11.86 (s, 1H, NH); 13 C NMR (DMSO-d6) δ 14.7, 17,9, 24.2, 33.8, 49.7, 55.5, 63.8, 11.8, 118.0, 119.4, 135.8, 136.4, 147.8, 166.6, 167.2, 168.2, 169.3; Anal. Calcd. for C 24 H 25 N 3 O 8 : C59.62; H, 5.21; N, 8.69. Found: C, 59.44; H, 5.08; N, 8.50.
EXAMPLE 7
(3-(3-Ethoxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl)propanoylamino) acetate
[0097] (3-(3-Ethoxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl) propanoylamino) acetate was prepared by the procedure of Example 1 from 3-(3-ethoxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl)propanehydroxamic acid (1.0 g, 2.6 mmol) and acetic anhydride(0.53 g, 5.2 mmol) in anhydrous acetonitrile (30 mL). The product was isolated as a white solid (0.5 g, 53.2 %): mp, 124.0-126.0° C.; 1 H NMR (DMSO-d6) δ 1.31 (t, J=6.8 Hz, 3H, CH 3 ), 2.07 (s, 3H, CH 3 ), 2.61 (s, 3H, CH 3 ), 3.15-3.35 (m, 2H, CH 2 ), 3.72 (s, 3H, OCH 3 ), 4.00 (q, J=6.4 Hz, 2H, OCH 2 ), 5.65 (t, J=7.7 Hz, 1H, NCH), 6.85-7.02 (m, 3H, Ar), 7.61-7.70 (m, 3H, Ar), 11.85 (s, 1H, NH); 13 C NMR (DMSO-d6) δ 14.6, 16.9, 17.9, 33.8, 49.6, 55.4, 63.7, 111.8, 112.2, 119.4, 120.7, 127.8, 131.1, 131.6, 134,0, 136.6, 137.3, 147.7, 148.5, 166.6, 167.5, 168.1, 168.2; Anal. Calcd. for C 23 H 24 N 2 O 7 : C, 62.72; H, 5.49; N, 6.36. Found: C, 62.79; H, 5.35; N, 6.26.
EXAMPLE 8
(3-(3-Ethoxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl)propanoylamino) acetate
[0098] (3-(3-Ethoxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl) propanoylamino) acetate was prepared analogously to Example 1 from 3-(3-ethoxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl)propanehydroxamic acid (0.90 g, 2.4 mmol) and acetic anhydride (0.48 g, 4.7 mmol) in anhydrous acetonitrile (27 mL). The product was obtained as a white solid (0.30 g, 30.0 %): mp, 145.0- 147.0 ° C.; 1 H NMR (DMSO-d6) δ 1.31 (t, J=6.9 Hz, 3H, CH 3 ), 2.07 (s, 3H, CH 3 ), 2.48 (s, 3H, CH 3 ), 3.20-3.36 (m, 2H, CH 2 ), 3.72 (s, 3H, OCH 3 ), 4.00 (q, J=6.4 Hz, 2H, OCH 2 ), 5.65 (t, J=7.2 Hz, 1H, CH), 6.89-7.00 (m, 3H, Ar), 7.62-7.76 (m, 3H, Ar), 11.84 (s, 1H, NH); 13 C NMR (DMSO-d6) δ 14.6, 17.9, 21.3, 33.9, 49.7, 55.4, 63.7, 111.8, 112.1, 119.3, 128.6, 131.1, 131.6, 134.9, 145.5, 147.7, 148.5, 166.6, 167.6, 167.7, 168.1; Anal. Calcd. for C 23 H 24 N 2 O 7 : C, 61.50; H, 5.36; N, 6.07. Found: C, 61.52; H, 5.46; N, 6.21.
EXAMPLE 9
(3-(3-Cyclopentyloxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl) propanoylamino) acetate
[0099] (3-(3-Cyclopentyloxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl) propanoylamino) acetate was prepared analogously to Example 1 from 3-(3-cyclopentyloxy -4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl) propanehydroxamic acid (1.5 g, 3.4 mmol) and acetic anhydride (0.7 g, 6.8 mmol) in anhydrous acetonitrile (45 mL). The product was obtained as a white solid (0.61 g, 43.3%): mp, 150.0-152.0° C.; 1 H NMR (DMSO-d6) δ 1.55-1.89 (m, 8H, C 5 H 8 ), 2.08 (s, 3H, CH 3 ), 2.61 (s, 3H, CH 3 ), 3.22-3.36 (m, 2H, CH 2 ), 3.71 (s, 3H, OCH 3 ), 4.50-4.74 (m, 1H, OCH), 5.65 (t, J=7.5 Hz, 1H CH), 6.89-7.02 (m, 3H, Ar), 7.58-7.70 (m, 3H, Ar), 11.86 (s, 1H, NH); 13 C NMR (DMSO-d6) δ 17.0, 17.9, 23.5, 32.1, 33.9, 49.6, 55.5, 79.6, 112.1, 114.0, 119.4, 120.7, 127.8, 131.1, 131.6, 134.0, 136.6, 137.3, 146.7, 149.2, 166.6, 167.5, 168.1, 168.3; Anal. Calcd. for C 26 H 28 N 2 O 7 : C, 64.25; H, 5.82; N, 5.75. Found: C, 64.13; H, 5.72; N, 5.55.
EXAMPLE 10
(3-(3-Cyclopentyloxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl) propanoylamino) acetate
[0100] (3-(3-Cyclopentyloxy-4-methoxyphenyl)-3-(5-methyl-1 ,3-dioxoisoindolin-2-yl) propanoylamino) acetate was prepared by the procedure of Example 1 from 3-(3-cyclopentyloxy -4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl) propanehydroxamic acid (1.0 g, 2.3 mmol) and acetic anhydride(0.47 g, 4.6 mmol) in anhydrous acetonitrile (30 mL). The product was obtained as a white solid (0.53 g, 48.5 %): mp, 98.0-101.0° C.; 1 H NMR (DMSO-d6) δ 1.50-1.95 (m, 8H, C 5 H 8 ), 2.07 (s, 3H, CH 3 ), 2.50 (s, 3H, CH 3 ), 3.10-3.26 (m, 2H, CH 2 ), 3.70 (s, 3H, OCH 3 ), 4.60-4.80 (m, 1H, OCH), 5.64 (t, J=7.7 Hz, 1H, CH), 6.88-7.01 (m, 3H, Ar), 7.61-7.76 (m, 3H, Ar), 11.86 (s, 1H, NH); 13 C NMR (DMSO-d6) δ 17.9, 21.3, 23.5, 32.1, 33.9, 49.8, 55.5, 79.5, 112.1, 113.9, 119.4, 123.0, 123.5, 128.6, 131.0, 131.6, 134.9, 145.5, 146.7, 149.1, 166.6, 167.6, 167.7, 168.1; Anal. Calcd. for C 26 H 28 N 2 O 7 : C, 64.68; H, 5.90; N, 5.80. Found: C, 64.47; H, 5.81; N, 5.62.
EXAMPLE 11
(N-Acetyl-3-(3-ethoxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl) propanoylamino) acetate
[0101] (N-Acetyl-3-(3-ethoxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl) propanoylamino) acetate was prepared by the procedure of Example 1 from 3-(3-ethoxy -4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl)propanehydroxamic acid (0.9 g, 2.3 mmol) and acetic anhydride (0.48 g, 4.7 mmol) in anhydrous acetonitrile (27 mL). The product was obtained as a white solid (0.06 g, 6%): mp, 128.0-129.5.° C.; 1 H NMR (DMSO-d6) δ 1.30 (t, J=6.8 Hz, 3H, CH 3 ), 2.26 (s, 3H, CH 3 ), 2.28 (s, 3H, CH 3 ), 2.50 (s, 3H, CH 3 ), 3.55-4.15 (m, 2H, CH 2 ), 3.72 (s, 3H OCH 3 ), 4.00 (q, J=6.8 Hz, 2H, OCH 2 ), 5.67 (t, J=3.3 Hz, 1H, CH), 6.89-7.00 (m, 3H, Ar), 7.62-7.76 (m, 3H, Ar); 13 C NMR (DMSO-d6) δ 14.6, 17.9, 21.3, 33.9, 49.7, 55.4, 63.7, 111.8, 112.1, 119.3, 128.6, 131.1, 131.6, 134.9, 145.5, 147.7, 148.5, 166.6, 167.6, 167.7, 168.1; Anal. Calcd. for C 25 H 26 N 2 O 8 : C, 62.23; H, 5.43; N, 5.81. Found: C, 61.83; H, 5.33; N, 5.53.
EXAMPLE 12
(N-Acetyl-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl)propanoylamino) acetate
[0102] (N-Acetyl-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl)propanoylamino) acetate was prepared by the procedure of Example 1 from 3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(4-methyl-1,3-dioxoisoindolin-2-yl) propanehydroxamic acid (1.5 g, 3.4 mmol) and acetic anhydride —( 0.7 g, 6.8 mmol) in anhydrous acetonitrile (45 mL). The product was obtained as a white solid (0.21 g, 12.8%): mp, 120.0-122.0° C.; 1 H NMR (DMSO-d6) δ 1.50-1.90 (m, 8H, C 5 H 8 ), 2.28 (s, 3H, CH 3 ), 2.29 (s, 3H, CH 3 ), 2.61 (s, 3H, CH 3 ), 3.71 (s, 3H, OCH 3 ), 3.50-4.10 (m, 2H, CH 2 ), 4.60-4.70 (m, 1H, OCH), 5.67 (t, J=8.9 Hz, 1H, CH), 6.80-7.10 (m, 3H, Ar), 7.50-7.75 (m, 3H, Ar); 13 C NMR (DMSO-d6) δ 17.0, 17.7, 23.5, 23.6, 23.7, 32.1, 49.0, 55.5, 79.6, 112.2, 113.9, 119.3, 120.8, 127.6, 131.1, 131.5, 134.2, 136.8, 137.4, 146.8, 149.2, 167.6, 167.7, 168.3; Anal. Calcd. for C 28 H 30 N 2 O 8 : C, 64.36; H, 5.79; N, 5.36. Found: C, 64.40; H, 5.73; N, 5.04.
EXAMPLE 13
(3-[5-(Acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl) propanoylamino) acetate
[0103] (3-[5-(Acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl) propanoylamino) acetate was prepared by the procedure of Example 1 from N-[2-[2-(N-hydroxycarbamoyl)-1-(3-ethoxy-4-methoxyphenyl)ethyl]-1,3-dioxoisoindolin-5-yl]acetamide (0.75 g, 1.7 mmol) and acetic anhydride (0.21 g, 2.0 mmol) in anhydrous acetonitrile (28 mL). The product was obtained as a white solid (0.60 g, 73%): mp, 178° C. (decomp.); 1 H NMR (DMSO-d6) δ 1.31 (t, J=7.0 Hz, 3H, CH 3 ), 2.07 (s, 3H, CH 3 ), 2.12 (s, 3H, CH 3 ), 3.19 (dd, J=7.1, 15 Hz, 1H, CHH), 3.23-3.43 (m, 1H, CHH), 3.72 (s, 3H, CH 3 ), 3.98 (q, J=7.0 Hz, 2H, CH 2 ), 5.63 (t, J=8.5 Hz, 1H, CH), 6.89 (s, 2H, Ar), 7.00 (s, 1H, Ar), 7.77-7.86 (m, 2H, Ar), 8.17 (d, J=1.1 Hz 1H, Ar), 10.56 (br s, 1H, NH), 11.85 (br s, 1H, NH); 13 C NMR (DMSO-d6) δ 14.6, 17.9, 24.2, 33.9, 49.8, 55.4, 63.7, 111.7, 112.1, 112.6, 119.3, 123.2, 124.3, 124.8, 131.1, 132.7, 144.8, 147.7, 148.5, 166.5, 167.2, 167.4, 168.1, 169.3; Anal. Calcd. for C 24 H 25 N 3 O 8 : C, 59.62; H, 5.21; N, 8.69. Found: C, 59.34; H, 5.30; N, 8.58.
EXAMPLE 14
(3-(1,3-Dioxobenzo[e]isoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl) propanoylamino) acetate
[0104] (3-(1,3-Dioxobenzo[e]isoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl) propanoylamino) acetate was prepared by the procedure of Example 1 from 3-(1,3-dioxobeno [e]isoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanehydroxamic acid (1.0 g, 2.3 mmol), acetic anhydride (0.50 mL, 5.3 mmol) in acetonitrile (30 mL). The product was obtained as a yellow solid (135 mg, 12% yield): mp, 180° C. (decomp); 1 H NMR (DMSO-d 6 ) δ 1.30 (t, J=6.9 Hz, 3H, CH 3 ), 2.04 (s, 3H, CH 3 ), 3.24 (dd, J=7.0, 15.1 Hz, 1H, CHH), 3.40 (dd, J=8.8, 15.1 Hz, 1H CHH), 3.71 (s, 3H, CH 3 )i 4.09 (q, J=7.1 Hz, 2H, CH 2 ), 5.72 (t, J=8.3 Hz,1H NCH), 6.89-6.99 (m, 2H, Ar), 7.06 (s, 1H, Ar), 7.72-7.89 (m, 3H, Ar), 8.17 (d, J=8 Hz, 1H, Ar), 8.40 (d, J=8.3 Hz, 1H, Ar), 8.79 (d, J=8.2 Hz, 1H, Ar), 11.90 (brs, 1H, NH); 13 C NMR (DMSO-d 6 ) δ 14.65, 17.87, 34.07, 43.73, 55.43, 63.71, 111.78, 112.20, 118.37, 119.38, 123.80, 126.22, 127.09, 128.79, 129.12, 129.81, 130.74, 131.11, 135.43, 136.16, 147.22, 148.52, 166.58, 168.05, 168.81; Anal Calcd for C 26 H 24 N 2 O 7 : C, 65.54; H, 5.08; N, 5.88. Found: C, 65.40; H, 5.27; N, 5.76.
EXAMPLE 15
(3-(3-Ethoxy-4-methoxyphenyl)-3-phthalimido-propanoylamino) pyridine-3-carboxylate
[0105] (3-(3-Ethoxy-4-methoxyphenyl)-3-phthalimido-propanoylamino) pyridine-3-carboxylate was prepared analogously to Example 1 from 3-(3-ethoxy-4-methoxyphenyl)-3-phthalimido-N-hydroxypropionamide (768 mg, 2.0 mmol), triethyl amine (0.7 mL, 5.0 mmol) and nicotinoyl chloride hydrochloride (391 mg, 2.2 mmol) in anhydrous acetonitrile (30 mL). The product was isolated as a white solid (250 mg, 26% yield): mp, 156.0-158.0° C.; 1 H NMR (DMSO-d 6 ) δ 1.32 (t, J=6.9 Hz, 3H, CH 3 ), 3.28-3.45 (m, 2H, CH 2 ), 3.73 (s, 3H, CH 3 ), 4.00 (q, J=6.9 Hz, 2H, CH 2 ), 5.71 (t, J=7.5 Hz, 1H, NCH), 6.92-6.93 (m, 2H, Ar), 7.05 (br s, 1H Ar), 7.59 (dd, J=4.8, 7.9 Hz, 1H, Ar), 7.82-7.90 (m, 4H, Ar), 8.28-8.32 (m, 1H, Ar), 8.86-8.88 (m, 1H, Ar), 9.06-9.07 (m, 1H, Ar), 12.32 (br s, 1H, NH); 13 C NMR (DMSO-d 6 ) δ 14.66, 33.87, 49.77, 55.45, 63.74, 111.83, 112.24, 119.45, 122.96, 123.17, 124.16, 130.97, 131.22, 134.60, 137.17, 147.75, 148.63, 149.97, 154.56, 162.92, 167.04, 167.64; Anal Calcd for C 26 H 23 N 3 O 7 +0.17 H 2 O: C, 63.40; H, 4.78; N, 8.53; H 2 O, 0.62. Found: C, 63.05; H, 4.64; N, 8.20; H 2 O, 0.62.
EXAMPLE 16
(3-[4-(Acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-cyclopentyloxy-4-methoxyphenyl) propanoylamino) acetate
[0106] (3-[4-(Acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-cyclopentyloxy-4-methoxyphenyl)propanoylamino) acetate was prepared by the procedure of Example 1 from N-[2-[2-(N-hydroxycarbamoyl)-1-(3-cyclopentyloxy-4-methoxyphenyl)ethyl]-1,3-dioxoisoindolin-4-yl]acetamide (1.3 g, 2.7 mmol), acetic anhydride (0.51 mL, 5.4 mmol) in acetonitrile (45 mL). The product was obtained as a yellow solid (95 mg, 7% yield): mp, 97.0-99.5° C.; 1 H NMR (DMSO-d 6 ) δ 1.55-1.85 (m, 8H, C 5 H 8 ), 2.07 (s, 3H, CH 3 ), 2.19 (s, 3H, CH 3 ), 3.18-3.37 (m, 2H, CH 2 ), 4.74 (m, 1H, OCH), 5.64 (t, J=7.7 Hz, 1H, NCH), 6.91 (br s, 2H, Ar), 7.00 (s, 1H, Ar), 7.56 (d, J=7.2 Hz, 1H, Ar), 7.77 (t, J=8.0 Hz, 1H, Ar), 8.40-8.47 (m, 1H, Ar), 9.71 (br s, 1H, NH, Ar), 11.86 (brs, 1H, NH); 13 C NMR (DMSO-d 6 ) δ 17.9, 23.5, 24.2, 32.1, 33.8, 49.7, 55.5, 79.6, 112.1, 114.0, 116.2, 117.9, 119.4, 125.8, 130.8, 131.4, 135.8, 136.1, 146.7, 149.2, 166.5, 167.1, 168.1, 169.2; Anal Calcd for C 27 H 29 N 3 O 8 : C, 61.94; H, 5.58; N, 8.03. Found: C, 61.59; H, 5,48; N, 7.88.
EXAMPLE 17
(N-Acetyl-3-[4-(acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-cyclopentyloxy-4-methoxyphenyl)propanoylamino) acetate
[0107] (N-Acetyl-3-[4-(acetylamino)-1,3-dioxoisoindolin-2-yl]-3-(3-cyclopentyloxy-4-methoxyphenyl)propanoylamino) acetate was prepared by the procedure of Example 1 from N-[2-[2-(N-hydroxycarbamoyl)-1-(3-cyclopentyloxy-4-methoxyphenyl)ethyl]-1,3-dioxoisoindolin-4-yl]acetamide (1.3 g, 2.7 mmol), acetic anhydride (0.51 mL, 5.4 mmol) in acetonitrile (45 mL). The product was obtained as a yellow solid (240 mg, 33% yield): mp, 93.0-95.0° C.; 1 H NMR (DMSO-d6) δ 1.55-1.85 (m, 8H, C 5 H 8 ), 2.19 (s, 3H, CH 3 ), 2.28 (s, 3H, CH 3 ), 2.30 (s, 3H, CH 3 ), 3.55-4.25 (m, 2H, CH 2 ), 4.74 (m, 1H, OCH), 5.68 (dd, J=2.8, 7.7 Hz, 1H, NCH), 6.91 (br s, 2H, Ar), 7.00 (s, 1H, Ar), 7.54-7.57 (m, 1H, Ar), 7.78 (t, J=7.6 Hz, 1H, Ar), 8.42-8.47 (m, 1H, Ar), 9.71 (br s, 2H, NH, Ar); 13 C NMR (DMSO-d 6 ) δ 17.8, 23.6, 24.4, 32.0, 32.1, 49.0, 55.6, 79.6, 112.1, 114.2, 116.5, 117.6, 118.1, 126.0, 130.8, 131.3, 135.8, 136.3, 146.8, 149.2, 167.1, 167.6, 168.1, 168.5, 169.1, 169.2; Anal Calcd for C 29 H 31 N 3 O 9 : C, 61.59; H, 5.52; N, 7.43. Found: C, 61.59; H, 5,46; N, 7.46.
EXAMPLE 18
(3-(3-Ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolin-2-yl)propanoylamino) acetate
[0108] (3-(3-Ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolin-2-yl)propanoylamino) acetate was prepared by the procedure of Example 1 from 3-(3-ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolin-2-yl)propanehydroxamic acid (500 mg, 1.35 mmol) and acetic anhydride (0.26 mL, 1.8 mmol) in anhydrous acetonitrile (20 mL). The product was obtained as a white solid (480 mg, 86%): mp, 131.5-134.0° C.; 1 H NMR (DMSO-d6); δ 1.29 (t, J=6.9 Hz, 3H, CH 3 ), 2.09 (s, 3H, CH 3 ), 3.04 (d, J=7.8 Hz, 2H, CH 2 ), 3.73 (s, 3H, CH 3 ), 3.97-4.04 (m, 2H, CH 2 ), 4.14 (d, J=17.5 Hz, 1H, NCHH), 4.58 (d, J=17.5 Hz, 1H, NCHH), 5.73 (t, J=7.8 Hz, 1H, NCH), 6.85-6.95 (m, 3H, Ar), 7.44-7.70 (m, 4H, Ar), 11.85 (s, 1H, NH); 13 C NMR (DMSO-d 6 ) δ 14.64, 17.89, 34.62, 46.37, 51.02, 55.43, 63.73, 111.86, 112.13, 119.14, 122.79, 123.36, 127.79, 131.29, 131.59, 132.17, 141.70, 147.88, 148.46, 166.58,166.89,168.30; Anal Calcd for C 22 H 24 N 2 O 6 : C, 64.07; H, 5.87; N, 6.79. Found: C, 63.96; H, 5.87; N, 6.58.
EXAMPLE 19
[0109] Tablets, each containing 50 mg of (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate are prepared in the following manner:
Constituents (for 1000 tablets) (3-(1,3-dioxoisoindolin-2-yl)- 50.0 g 3-(3-ethoxy-4-methoxyphenyl) propanoylamino) propanoate lactose 50.7 g wheat starch 7.5 g polyethylene glycol 6000 5.0 g talc 5.0 g magnesium stearate 1.8 g demineralized water q.s.
[0110] The solid ingredients are first forced through a sieve of 0.6 mm mesh width. The active ingredient, lactose, talc, magnesium stearate and half of the starch then are mixed. The other half of the starch is suspended in 40 mL of water and this suspension is added to a boiling solution of the polyethylene glycol in 100 mL of water. The resulting paste is added to the pulverulent substances and the mixture is granulated, if necessary with the addition of water. The granulate is dried overnight at 35° C., forced through a sieve of 1.2 mm mesh width and compressed to form tablets of approximately 6 mm diameter which are concave on both sides.
EXAMPLE 20
[0111] Tablets, each containing 100 mg of (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate can be prepared in the following manner:
Constituents (for 1000 tablets) (3-(1,3-dioxoisoindolin-2-yl)- 100.0 g 3-(3-ethoxy-4-methoxyphenyl) propanoylamino) propanoate lactose 100.0 g wheat starch 47.0 g magnesium stearate 3.0 g
[0112] All the solid ingredients are first forced through a sieve of 0.6 mm mesh width. The active ingredient, lactose, magnesium stearate and half of the starch then are mixed. The other half of the starch is suspended in 40 mL of water and this suspension is added to 100 mL of boiling water. The resulting paste is added to the pulverulent substances and the mixture is granulated, if necessary with the addition of water. The granulate is dried overnight at 35° C., forced through a sieve of 1.2 mm mesh width and compressed to form tablets of approximately 6 mm diameter which are concave on both sides.
EXAMPLE 21
[0113] Tablets for chewing, each containing 75 mg of (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate can be prepared in the following manner:
Composition (for 1000 tablets) (3-(1,3-dioxoisoindolin-2-yl)- 75.0 g 3-(3-ethoxy-4-methoxyphenyl) propanoylamino) propanoate mannitol 230.0 g lactose 150.0 g talc 21.0 g glycine 12.5 g stearic acid 10.0 g saccharin 1.5 g 5% gelatin solution q.s.
[0114] All the solid ingredients are first forced through a sieve of 0.25 mm mesh width. The mannitol and the lactose are mixed, granulated with the addition of gelatin solution, forced through a sieve of 2 mm mesh width, dried at 50° C. and again forced through a sieve of 1.7 mm mesh width. (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate, the glycine and the saccharin are carefully mixed, the mannitol, the lactose granulate, the stearic acid and the talc are added and the whole is mixed thoroughly and compressed to form tablets of approximately 10 mm diameter which are concave on both sides and have a breaking groove on the upper side.
EXAMPLE 22
[0115] Tablets, each containing 10 mg (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate can be prepared in the following manner:
Composition (for 1000 tablets) (3-(1,3-dioxoisoindolin-2-yl)- 10.0 g 3-(3-ethoxy-4-methoxyphenyl) propanoylamino) propanoate lactose 328.5 g corn starch 17.5 g polyethylene glycol 6000 5.0 g talc 25.0 g magnesium stearate 4.0 g demineralized water q.s.
[0116] The solid ingredients are first forced through a sieve of 0.6 mm mesh width. Then the active imide ingredient, lactose, talc, magnesium stearate and half of the starch are intimately mixed. The other half of the starch is suspended in 65 mL of water and this suspension is added to a boiling solution of the polyethylene glycol in 260 mL of water. The resulting paste is added to the pulverulent substances, and the whole is mixed and granulated, if necessary with the addition of water. The granulate is dried overnight at 35° C., forced through a sieve of 1.2 mm mesh width and compressed to form tablets of approximately 10 mm diameter which are concave on both sides and have a breaking notch on the upper side.
EXAMPLE 23
[0117] Gelatin dry-filled capsules, each containing 100 mg of (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate can be prepared in the following manner:
Composition (for 1000 capsules) (3-(1,3-dioxoisoindolin-2-yl)- 100.0 g 3-(3-ethoxy-4-methoxyphenyl) propanoylamino) propanoate microcrystalline cellulose 30.0 g sodium lauryl sulfate 2.0 g magnesium stearate 8.0 g
[0118] The sodium lauryl sulfate is sieved into the (3-(1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl) propanoylamino) propanoate through a sieve of 0.2 mm mesh width and the two components are intimately mixed for 10 minutes. The microcrystalline cellulose is then added through a sieve of 0.9 mm mesh width and the whole is again intimately mixed for 10 minutes. Finally, the magnesium stearate is added through a sieve of 0.8 mm width and, after mixing for a further 3 minutes, the mixture is introduced in portions of 140 mg each into size 0 (elongated) gelatin dry-fill capsules.
EXAMPLE 24
[0119] A 0.2% injection or infusion solution can be prepared, for example, in the following manner:
(3-(1,3-dioxoisoindolin-2-yl)- 5.0 g 3-(3-ethoxy-4-methoxyphenyl) propanoylamino) propanoate sodium chloride 22.5 g phosphate buffer pH 7.4 300.0 g demineralized water to 2,500.0 mL
[0120] (3-(1,3-Dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino) propanoate is dissolved in 1000 mL of water and filtered through a microfilter. The buffer solution is added and the whole is made up to 2500 mL with water. To prepare dosage unit forms, portions of 1.0 or 2.5 mL each are introduced into glass ampoules (each containing respectively 2.0 or 5.0 mg of imide).
EXAMPLE 25
(3-(4-Acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino)propanate
[0121] (3-(4-Acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-propanoylamino)propanate was prepared by the procedure used for example 1 from 3-(4-acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propane-hydroxamic acid (1 g, 2.26 mmol) and propionic anhydride (0.59 g, 4.53 mmol) in anhydrous acetonitrile (30 mL). The product was obtained as a white solid (0.96 g, 87%): mp, 147-149° C.; 1 H NMR (DMSO-d 6 ) δ 11.86 (s,1H), 9.70 (s,1H), 8.43 (d, J=8.4 Hz, 1H), 7.77 (t, J=7.7 Hz, 1H), 7.55 (d, J=7.3 Hz, 1H), 7.00-6.91 (m, 3H), 5.65 (t, J=7.5 Hz, 1H), 4.01 (q, J=6.9 Hz, 2H), 3.72 (s, 3H), 3.34-3.24 (m, 2H), 2.38 (q, J=7.5 Hz, 2H), 2.19 (s, 3H), 1.31 (t, J=7.0 Hz, 3H), 1.02 (t, J=7.4 Hz, 3H); 13 C NMR (DMSO-d 6 ) δ 171.63, 169.19, 168.15, 167.09, 166.59, 148.61, 147.74, 136.40, 138.73, 131.41, 130.80, 125.75, 119.38, 117.95, 116.62, 112.24, 111.79, 63.77, 55.45, 49.62, 33.75, 24.25, 24.19, 14.66.8.68; Anal. Calcd. For C 25 H 27 N 3 O 8 : C, 60.36; H, 5.47; N, 8.45. Found: C, 60.26; H, 5.45; N, 8.39.
EXAMPLE 26
(3-(4-Acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino)butanoate
[0122] (3-(4-Acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-propanoylamino)butanoate was prepared by the procedure used for example 1 from 3-(4-acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-propanehydroxamic acid (1.0 g, 2.26 mmol) and butyric anhydride (0.72 g, 4.53 mmol) in anhydrous acetonitrile (30 mL). The product was obtained as a white solid (0.93 g, 80%): mp, 105-107° C.; 1 H NMR (DMSO-d 6 ) δ 11.84 (s, 1H), 9.69 (s, 1H), 8.42 (d, J=7.5 Hz, 1H), 7.77 (t, J=7.6 Hz, 1H), 7.55 (d, J=7.2 Hz, 1H), 6.99-6.91 (m, 3H), 5.64 (t, J=7.5 Hz, 1H), 4.00 (q, J=7.0 Hz, 2H), 3.72 (s, 3H), 3.31-3.24 (m, 2H), 2.35 (t, J=7.2 Hz, 2H), 2.18 (s, 3H), 1.51 (q, J=7.3 Hz, 2H), 1.31 (t, J=7.0 Hz, 3H), 0.86 (t, J=7.4 Hz, 3H); 13 C NMR (DMSO-d 6 ) δ 170.95, 169.18, 168.09, 166.60, 148.60, 147.73, 136.40, 135.74, 131.42, 130.80, 125.75, 119.36, 117.96, 116.63, 112.22, 111.79, 63.70, 55.46, 49.61, 33.79, 32.56, 24.19, 17.80, 14.66, 13.14; Anal. Calcd. For C 26 H 29 N 3 O 8 : C, 61.05: H, 5.71; N, 8.21. Found: C, 60.95; H, 5.73; N, 7.97
EXAMPLE 27
(3-(4-Acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino)benzoate
[0123] (3-(4-Acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-propanoylamino)benzoate was prepared by the procedure used for example 1 from 3-(4acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-propane-hydroxamic acid (1.0 g, 2.26 mmol) and benzoic anhydride (1.02 g, 4.52 mmol) in anhydrous acetonitrile (30 mL). The product was obtained as a white solid (1.05 g, 55%): mp, 150-152° C.; 1 H NMR (DMSO-d 6 ) δ 12.19 (s, 1H), 9.71 (s, 1H), 8.44 (d, J=8.4 Hz, 1H), 7.96-7.52 (m, 7H), 7.04-6.91 (m, 3H), 5.70 (t, J=7.5 Hz, 1H), 4.03 (q, J=6.9 Hz, 2H), 3.74 (s, 3H), 3.44-3.28 (m, 2H), 2.19 (s, 3H), 1.32 (t, J=6.9 Hz, 3H); 13 C NMR (DMSO-d 6 ) δ 169.20, 168.17, 167.13, 166.93, 163.87, 148.62, 147.75, 136.42, 135.76, 134.31, 131.44, 130.79, 129.38, 129.05, 126.60, 125.80, 119.39, 118.00, 116.67, 112.24, 111.81, 63.77, 55.47, 49.60, 33.77, 24.20, 14.67; Anal. Calcd. For C 29 H 27 N 3 O 8 : C, 63.85; H, 4.99; N, 7.70. Found: C, 63.86; H, 4.98; N, 7.45.
EXAMPLE 28
(3-(4-Acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoylamino)isobutanoate
[0124] (3-(4-Acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-propanoylamino)isobutanoate was prepared by the procedure used for example 1 from 3-(4-acetylamino-1,3-dioxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-propanehydroxamic acid (1.0 g, 2.26 mmol) and isobutyric anhydride (0.72 g, 4.52 mmol) in anhydrous acetonitrile (30 mL). The product was obtained as a white solid (1.02 g, 87%): mp, 104-106° C.; 1 H NMR (DMSO-d 6 ) δ 11.84 (s, 1H), 9.70 (s, 1H), 8.42 (d, J=8.4 Hz, 1H), 7.77 (t, J=7.5 Hz, 1H), 7.56 (d, J=7.2 Hz, 1H), 6.99-6.91 (m, 3H), 5.64 (t, J=7.5 Hz, 1H), 4.00 (q, J=7.0 Hz, 2H), 3.72 (s, 3H), 3.33-3.25 (m, 2H), 2.68-2.62 (m, 1H), 2.19 (s, 3H), 1.31 (t, J=7.0 Hz, 3H), 1.15-1.04 (m, 6H); 13 C NMR (DMSO-d 6 ) δ 174.10, 169.18, 168.11, 167.06, 166.66, 148.60, 147.72, 136.40, 135.73, 131.40, 130.80, 125.77, 119.36, 117.96, 116.62, 112.24, 111.79, 63.75, 55.45, 49.54, 33.78, 31.20, 24.17, 18.58, 14.54; Anal. Calcd. For C 26 H 29 N 3 O 8 : C, 61.05; H, 5.71; N, 8.21. Found: C, 60.97; H, 5.83; N, 7.96.
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Imido and amido substituted acyihydroxamidic acids which reduce the levels of TNFα and inhibit phosphodiesterase in a mammal. A typical embodiment is (3-(1,3-dioxoisoindolin -2-yl)-3-(3-ethoxy-4-methoxyphenyl)propandylamino)propanoate.
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BACKGROUND OF THE INVENTION
This invention relates to a bathing device.
Conveniently, a bath or shower to wash is taken in a bath or shower which is a fixture. Persons also take Turkish baths, where the person is enveloped in hot moist steam, or a sauna bath, where a person is immersed in hot air and intermittently subjected to hot dry steam. Again such baths are taken in a fixture.
SUMMARY OF THE INVENTION
The object of the invention is to provide a bathing device which renders more convenient the taking of all the above mentioned types of baths, particularly, but not exclusively, in a domestic environment.
According to the invention we provide a bathing device comprising a cabinet having an upper casing part with an access opening, means at least substantially to close the opening, a seat within the upper part on which a person can sit, and means providing an aperture through which the head of the person can project, and a lower casing part containing a reservoir for water, a heating element, means to supply water from the reservoir to the heating element to generate steam, means to supply water from the reservoir to the interior of the cabinet to wash a person, a holding tank for used water, and means to collect the used water and deliver it to the holding tank.
A heating means may be provided to heat the water in the reservoir or the water delivered from the reservoir for washing.
Control means may be provided to permit of heating air within the cabinet, for feeding water intermittently to a heating element to provide a sauna bath, for feeding water continuously to the heating element to provide a Turkish bath and for feeding water for washing.
Preferably, said control means and/or heating means are provided in said lower casing part.
The lower casing part may comprise a top wall surrounded by a downwardly depending side wall, the top wall having two recesses formed therein one of which provides said water reservoir and the other of which provides said holding tank.
The top wall may have an upwardly projecting part which extends into the interior of the upper casing part and is adapted to provide an electrical supply means to the heating element.
Preferably, the upper and lower casing parts are made as mouldings in suitable synthetic plastics material such as grp.
Preferably, the closure means for the access opening comprises a flexible sheet which substantially closes the opening except for a region which provides the said aperture through which the person's head may project.
Preferably the flexible sheet comprises two portions with a fastening means such as a zip fastening therebetween; the parts of the sheet being fixed to the upper casing part adjacent the edge of the access opening.
Preferably, the upper and lower casing parts comprise one-piece mouldings in said plastics material and said reservoir and holding tank are formed integrally with the remainder of the lower casing part.
BRIEF DESCRIPTION OF THE DRAWINGS
One embodiment of the invention will now be described in detail by way of example only with reference to the accompanying drawings wherein:
FIG. 1 is a broken away perspective view of a bathing device embodying the invention;
FIG. 2 is a diagrammatic representation illustrating the water flow bath for the device of FIG. 1.
DESCRIPTION OF PREFERRED EMBODIMENT
Referring to FIG. 1, the bathing device is generally indicated at 10 and comprises an upper casing part 11 and a lower casing part 12 each made as one-piece mouldings in a suitable synthetic plastics material such as grp.
The lower casing part 12 provides the base of the unit and has projecting from its under surface a pair of castors 13 at its forward end and a pair of feet 14 at its rearward end. The lower casing part 12 has a generally horizontal top wall 15 from which a downwardly depending side wall 16 depends. The lower casing part 12 is of generally rectangular configuration in plan view and hence the side wall 16 has four orthogonally arranged portions 16a, 16b, 16c and 16d.
The top wall 15 has formed integrally therewith two recesses 17, 18. The recess 17 provides a generally rectangular open-topped reservoir for fresh water and the recess 18 provides a similar rectangular in plan view open-topped holding tank for used water.
At each side of the lower casing part, the top wall 15 is formed with an upwardly projecting portion 19, 20 which has generally vertically upstanding side walls 21 and a generally horizontal top wall 22. One of the side walls 21 provides a continuation of the side wall 16b of the casing part 12 and has an aperture 23 therein in which is received a control panel 24 whilst the space 25 within the projecting part 19 accommodates the control elements behind the panel 23 as hereinafter to be described.
Also projecting upwardly from the upper wall 15 is a plinth 26 at a location adjacent the mid-point of the rear side wall 16c of the base but spaced inwardly from the side wall 16c so that it can project through an aperture 27 formed in a generally horizontal base wall 28 of the upper casing part 11.
The plinth 26 has a sheathed electrical connection 29 extending forwardly therefrom to provide electrical power supply to a heating plate 30 as hereinafter to be described.
Mounted within the reservoir 17 is a conventional electrical immersion heating element 31 and a thermostat 32. A pipe 33 extends from the lower end of the reservoir 17 to an electrically operated pump 34 from which a delivery pipe 35 extends which branches into a return pipe 36 to the reservoir 17 and a fresh water delivery pipe 37 which extends beneath the top wall 15 and then upwardly within the upper casing part 11 to a shower control valve 38 and is branched, as shown at 39 to a steam control valve 40. Downstream of the valve 40, a water delivery pipe 41 extends within the upper casing part 11 to a position below a seat 42 provided therein and terminates in a spray head 43 to deliver water to the upper surface of the heating plate 30.
Also mounted below the upper wall 15 within the lower casing part 12 is a further pump 44 to which used water is fed from the holding tank 18 by a pipe 45 and which is arranged to deliver the used water via a pipe 46 to a connector 47 to which a flexible hose may be connected to permit the waste water to be pumped from the holding tank 18 either directly into a drain or into a portable container or otherwise as desired.
The upper casing part 11 comprises generally planar lateral side walls 50 and a back wall 51, together with a front wall 52 the lower part of which extends vertically upwardly as indicated at 53 and the upper part of which is inclined upwardly and rearwardly as indicated at 54 and merges with a generally horizontal top wall 55. An access opening 56 is formed in the front wall 52 and is arranged to be closed by flexible sheets 57a, 57b connected to the upper casing part 11 around the periphery of the opening 56 and arranged to be connected together by a sliding clasp fastening 58. The sheets 57a, 57b do not completely close the opening 56 but provide an aperture 59 through which the head of a person sitting on the seat 42 can project with the sheets 57a, 57b engaged closely around the neck of the person to provide a seal for the environment within the casing parts.
As mentioned previously, the upper casing part 11 has a generally horizontal lower wall 28 provided with the aperture 27 and also having box-like projections 61, 62 to accommodate the upstanding parts 19 and 20 respectively of the lower casing part. The wall 28 is also provided with a filler aperture closed by a cap 63 to permit access to be gained to the lower casing part whereby the reservoir 17 can be filled.
Supported on the wall 28 is the heating plate 30 which comprises a metal, generally rectangular, plate 30a heated by an electrical heating element therebeneath (not shown); the plate 30 is supported on legs 31a of heat insulating material from the wall 28 and is located beneath the seat 42 which comprises a suitable piece of wood or if desired moulding of synthetic plastics material, at a desired height by being slid between desired ribs 64 formed integrally in the side walls 50 of the upper casing part 11.
As mentioned previously, mounted within the upper casing part 11 are spray and steam control valves 38, 40. Connected to the spray valve 38 is a conventional flexible hose 65 having at its end a conventional hand-held shower head 66. A handle 67 is provided in a recess 68 on each side of the upper casing part 11 adjacent the rear thereof to permit the bathing device to be moved by lifting the rear feet 14 from the ground and rolling the device on the castors 13. The overall dimensions are such that the device can be passed through standard doorways of a house.
The edge of the access opening 56 is preferably provided with a foamed plastics material moulding to provide a smooth and soft edge to avoid any possibility of discomfort to a user on entry into the device.
The lower wall 28 provides, of course, a lid for the reservoir 17 and holding tank 18.
The underside of the lower casing part 12 is closed by a removable plate (not shown) to prevent inadvertent access to the controls, pumps and electric wiring etc. The upper and lower casing parts are bonded together using a suitable bonding agent. If desired, a timing device may be provided in the main electric supply to the device so that it is switched off after a predetermined period of time, for example half an hour, in case a user of the device forgets to switch it off and to avoid thereby any risk of damage due to overheating. Furthermore, if desired, thermostats may be provided within the device at appropriate positions to avoid overheating.
The control panel may be provided with a warning light to indicate the device is connected to a supply of electric power and a switch provided for the fresh water pump 34 and for the used water pump 44 as well as for the immersion heater element 31 and the heating plate 30. If desired, all these switches may be arranged to illuminate an indicator light when their function is operative. If desired, a switch may be provided with an interlock so that only one source of power is operated at a time to avoid overloading of the power supply. For example, if the heating plate 30 is switched on energisation of the immersion heater element is prevented. Of course, if a higher current supply than the normal 13 amp domestic supply is available, for example a 30 amp supply, such an interlocking arrangement need not be provided.
The heating plate 30 in the present example is not thermostatically controlled, the temperature of the heating plate being limited by the loss of heat due to radiation, conduction and convection. On the other hand the immersion heater element 31 is thermostatically controlled to ensure that the water in the tank 17 is not raised above a predetermined temperature.
If desired, portable containers may be provided with the bathing device so that the correct amount of water can be conveniently carried to and fed into the reservoir 17 to permit the holding tank 18 to be conveniently emptied of the water therefrom into one of the containers using the pump 44 and a flexible hose connected to the connector 47.
If desired, a pressure release valve may be provided in the pipe 38 so that water is recirculated through the reservoir 17 to ensure mixing and hence uniform temperature of the water. If however the tap 38 or the tap 40 is opened, the pressure release valve will close and water will preferentially be fed through which ever of the taps is open.
If desired, the valve 40 may be spring loaded so that it automatically returns to a closed position when not maintained open by the user whilst the tap 38 is preferably of the conventional type which will remain in any position to which it is set by the user.
The heating plate 30 may be provided with a raised rim to retain water spread thereon.
Suitable protective bars or grills are provided beneath the seat 42 to prevent inadvertent access to the heating plate 30.
To provide a good seal for the flexible covers 57a and 57b on the neck of a user, preferably two relatively rigid semi-circular members are secured to the cover parts 57a, 57b and are pivoted together at the end thereof distant from the sliding clasp fastener 58. Within the semi-circular parts are provided two semi-circular rubber diaphragm members so that when a user of the apparatus closes the semi-circular units around his neck, the rubber diaphragm members deform to permit the closure to take place and to provide a sealing engagement with the user's neck.
The bottom wall 28 of the upper body part 11 is preferably provided with a plurality of downwardly projecting ribs which form depressions on the upper surface which act both to strengthen the floor and give it rigidity and also as drainage channels for the used water and an opening is provided in the floor 28 above the holding tank 18 which is closed by a grid to permit used water to drain into the holding tank 18.
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A bathing device (10) comprises a cabinet having an upper part (11) with an access opening (56) and a seat within the cabinet on which a person can sit, means (59) at least substantially to close the opening (56), means providing an aperture through which the head of the person can project, and a lower casing part (12) containing a reservoir (17) for water, a heating element (30), means (34) to supply water from the reservoir to the heating element (30) to generate steam, means to supply water from the reservoir (17) to the interior of the cabinet to wash a person, a holding tank (18) for used water, and means to collect the used water and deliver it to the holding tank (18).
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This invention relates to the isolation and recovery of anthocyanin from botanical sources, such as grape wastes (pomace). More particularly, it relates to the recovery of anthocyanin from plant materials by extraction with alcoholic tartaric acid solution, followed by precipitation of excess tartaric acid as potassium acid tartrate.
BACKGROUND OF THE INVENTION
The anthocyanins are glycosides of soluble coloring materials of plants. They are water-soluble pigments which are dissolved in the cell sap of plants. The various shades of red, blue, purple and violet of fruits and flowers are due to these pigments. The variations in color are due to slight alterations in the molecule which do not affect the fundamental chemical structure. The anthocyanins are amphoteric and form salts with both acids and bases. They usually occur as mixtures which vary from plant to plant. The color of the pigment is determined by the pH of the medium in which it is dissolved.
As natural products which occur in most fruits and leaves, the anthocyanins are desirable coloring agents for foods and drinks for human consumption. They have very low toxicity which gives them advantages over synthetic coloring agents for food products.
The conventional method of anthocyanin recovery from plant materials involves extraction with dilute alcohol solution of HCl, purification by ion-exchange and acid stabilization (Chiriboga and Franics, J. Am. Soc. Hort. Sci., 95(2):233-236, 1970). The mineral acid used for the elution and stabilization of anthocyanins limits the utilization of extracted anthocyanins due to the low pH imparted when added to food products. Ion-exchange purification is tedious and the cationic resins normally used to purify the anthocyanins also concentrate undesirable metal ions in the recovered anthocyanin. Weak cationic exchangers have low pigment capacity, and strong cationic exchangers, though excellent anthocyanin absorbers, require large volumes of solvent for complete elution of anthocyanins.
This invention has the advantage of avoiding mineral acids and ion-exchange materials which have previously been used in isolating anthocyanins from plants. This specification describes a new procedure for anthocyanin recovery from grape wastes based on tartaric acid-alkanol (methanol) extraction followed by precipitation of excess tartaric acid as potassium hydrogen tartrate. The centrifuge residue and wine grape pomace are wastes generated during the production of grape juice and wine, respectively. Their high anthocyanin and low sugar contents make it possible to recover the anthocyanins by the method described in this specification.
SUMMARY OF THE INVENTION
In accordance with my invention the grape wastes (solids remaining after removal of grape juice and including pomace and other residues from grape juice) are extracted with an alkanol solution of tartaric acid, the concentration of the tartaric acid varying from 0.01% (w/w) to about 2.5% (w/w) depending upon the type of waste used as a starting material. The alkanol can contain one or two carbon atoms and includes methanol and ethanol, preferably in anhydrous condition. The grape wastes are contacted with the alcoholic tartaric acid solution, preferably by leaching in a column, although any other method of contacting the grape waste with the alcohol solution such as agitation in a tank and decanting the supernatant liquid could be used. The alcoholic extract of the grape wastes is clarified, such as by filtration or centrifugation, to remove insoluble materials.
The tartaric acid in the alcoholic extract is then partially neutralized with potassium hydroxide, potassium carbonate, or potassium bicarbonate until approximately 80% to 95% of the tartaric acid is converted to potassium hydrogen tartrate (cream of tartar). The latter is insoluble in the alcoholic solution and precipitates when the solution is at 25°C. or lower. The precipitate of potassium acid tartrate is removed and the resulting alcoholic solution is evaporated, preferably under vacuum at a temperature not greater than 40°C., until the alcohol is removed. The remaining aqueous solution (containing water absorbed from the grape wastes) is then cooled to 15°C. or lower and a further precipitate of potassium acid tartrate is formed which again is removed.
The resulting aqueous solution of the anthocyanin can be used directly as a coloring material for food and drink for human consumption. The pH of the alcoholic solution and the aqueous solution should be maintained at 4 or below during the operations described above to avoid degradation of the anthocyanin.
DETAILED DESCRIPTION OF THE INVENTION
Red wine grape pomace (vinifera) was obtained from E & J Gallo Winery, Modesto, Calif. Centrifuge residues were obtained by clarifying freshly prepared Beauty Seedless grape (vinifera) juice through a centrifuge. Centrifuge residue and pomace had low sugar contents. Both were rich sources of anthocyanins and were wastes generated during the processing of grapes.
The centrifuge residues and pomace were dried in a vacuum oven (80° and 25 inches Hg) to moisture levels below 10% (w/w). Dried centrifuge residue (100 g) was packed in a column (2 × 40 cm) and extracted three times with methanol containing 0.1% (w/w) tartaric acid (100 ml each) at the flow rate of 5 ml per minute. The dried pomace (1 kg) was extracted in the same way with methanol containing 1% (w/w) tartaric acid (1 liter each) in a higher column (6 × 120 cm) and a higher flow rate of 25 ml per minute.
The methanol extracts were partially neutralized with 40% KOH solution so that a residual acidity of 10-15% of total tartaric acid used was maintained to prevent degradation of anthocyanins. The amount of potassium hydroxide required was calculated based on the equation:
KOH + tartaric acid → KH tartrate + H.sub.2 O.
the extracts were cooled to 15°C. and the precipitated potassium hydrogen tartrate (cream of tartar) was filtered off. The filtrate was evaporated under vacuum at 40°C. until all the methanol was removed. The aqueous anthocyanin concentrate was cooled to 10°-15°C. and filtered to remove potassium hydrogen tartrate precipitated during concentration.
The properties of the recovered anthocyanin concentrates from centrifuge residues and pomace are summarized in Table 1.
TABLE 1__________________________________________________________________________PROPERTIES OF ANTHOCYANIN CONCENTRATERECOVERED FROM GRAPE WASTES pH of solution obtained by Anthocyanin diluting 1 ml Yield/100 g concentration.sup.a Soluble solids Acidity of concentrateSource dry material per 100 ml (° Brix) (% tartaric acid) with 100 ml of Flavor water__________________________________________________________________________Centrifugeresidue 15 ml 0.80 g 16.0 5.6 3.1 NonePomace 20 ml 0.65 g 12.8 8.0 3.0 Slight fermented odor__________________________________________________________________________ .sup.a Anthocyanin concentration was calculated as malvidin 3-glucoside (E.sub.1cm.sup.1% = 524.4 in 0.01% conc. HCl/MeOH at 536 nm). Both the concentrates showed absorption maxima at 536 nm in 0.01% conc. HCl/MeOH. The spectral measurements were taken with a Perkin-Elmer 202 UV-Visible Spectrophotometer.
The acceptability of the anthocyanin extract was evaluated by preparing an artificial grape drink (°Brix = 13.0 and pH = 3.0) containing water, sucrose, tartaric acid, artificial grape flavor (Firmenich 59.469/A) and colored with the anthocyanin concentrate. This artificial grape drink colored with the concentrate (1.0 - 1.5 ml concentrate per 100 ml drink) gave a normal red grape juice color which was found to be acceptable by a panel of three judges. The slight fermented flavor of concentrate from pomace was not objectionable in the artificial grape drink. The sugar in the grape wastes is partially extracted by the aqueous alcohol and remains in the aqueous concentrate containing anthocyanin. It is innocuous in coloring agents for beverages. Sugar concentrations of 20% (w/w) in the concentrates are acceptable.
The concentration of tartaric acid required for efficient extraction depends on the material to be extracted. The centrifuge residue can be extracted with a low percentage of tartaric acid, whereas pomace requires higher amounts of tartaric acid. The pomace can be dehydrated with methanol (1 liter/1 kg) instead of drying in an oven without significant loss of anthocyanins. Dehydration with methanol removes part of the flavor associated with fermented pomace. Dehydration of centrifuge residue with methanol results in considerable loss of anthocyanins and should be avoided. The acidity of the final concentrate can be controlled to the desired degree by neutralization of tartaric acid. The two-stage neutralization of acid before and after removal of methanol is preferable to a single neutralization step before the removal of methanol.
This method is amenable to continuous process and the solvent can be recovered and reused. The potassium hydrogen tartrate generated during the recovery process is a valuable by-product. The tartaric acid present in the extract is not objectionable in food products where anthocyanins can be used for coloring.
Because the aqueous concentrate containing anthocyanin contains sugar (usually 5% to 20% w/w) extracted from the grape waste, it is often difficult to prepare a dry anthocyanin product by evaporation of water from the concentrate. Usually the sugar forms a syrup which does not crystallize. In such case, however, a dry powder for use as a coloring agent for beverages can be produced by admixing 1 ml of the concentrate with 15 grams of crystalline sugar. This product can be dissolved in 100 ml of water and produces a satisfactory grape color with sufficient sugar for palatable sweetness for beverage purposes.
In addition to grape wastes, other sources of anthocyanins which can be used as starting materials for this invention include most of the leaf and fruit portions of plants which contain anthocyanins, particularly malvidin glucoside. Other suitable fruit wastes include those from cherries, cranberries and plums, particularly the cherry plum, Prunus cerasifera. Particularly valuable as sources of anthocyanins are the fleshy calyxes of roselle, an Indian herb (Hibiscus sabdariffa) and the tropical African fruits known as miraculous fruit or miraculous berry which are of the family Sapotaceae, and include Synsepalum dulcificum which has a fruit which is a fleshy single-seeded berry, and a herb (Thaumatococcus daniellii) of the family Marantaceae whose fruit is a jellylike aril surrounding the seeds. Suitable botanical sources of anthocyanins are also described by Baker et al., Food Product Development, 8, No. 3, 83-87 (1974). Any of the botanical sources of anthocyanins can be treated in accordance with this invention to provide anthocyanin pigments suitable for food and beverage coloring agents.
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A new anthocyanin recovery system from plant materials such as grape wastes based on tartaric acid-alkanol extraction followed by controlled precipitation of excess tartaric acid as potassium hydrogen tartrate is described. An artificial grape drink colored with the anthocyanin extract thus prepared was found to be acceptable.
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BACKGROUND OF THE INVENTION
This invention relates to slip-casting.
Slip-casting is a known technique for casting ceramic articles in which a finely ground ceramic in a liquid suspension, or slip, is poured into a porous mold which absorbs the liquid and leaves a layer of ceramic deposited on the mold walls. When the desired thickness of ceramic is obtained, the excess liquid is poured out. The deposited casting is allowed to dry before being removed for sintering. The conventional mold material is plaster.
The use of plaster molds for slip casting has a number of limitations. It is very difficult to obtain thin molded castings, or articles having a large contact area with the mold, without breaking or cracking. Also, many ceramics, such as β-alumina, are difficult to remove from plaster molds since the castings tend to stick to the mold walls, even with the use of additives such as glycerine or sodium alginate. Moreover, the use of additives to facilitate demolding adversely affects the purity and porosity of the article. Also, casting in plaster molds is time-consuming, the molds must be dried between castings, and must be replaced after about five castings since the pores become clogged.
SUMMARY OF THE INVENTION
It has been found that a finely ground powder of ceramic material can be utilized as a mold for slip-casting, facilitating the casting procedure and particularly facilitating the removal of the casting from the mold.
The present invention provides a slip-casting system which comprises:
providing a powder of ceramic material, said powder having a particle size sufficiently small to provide shape retention upon compaction and retain the suspended particles of a slip, and said powder being inert to the slip;
shaping and compacting the powder to provide a mold cavity that conforms in shape to that of a desired casting;
introducing a slip into the mold cavity, retaining the slip for a time sufficient to form the desired thickness of the casting, and removing the remaining slip;
allowing at least partial drying of the casting; and
separating the casting from the powder.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a cross-sectional view illustrating an embodiment of apparatus for the slip-casting system of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIG. 1, the slip-casting system of the present invention utilizes a ceramic powder 1 for the mold which is shown contained by a suitable container 2. The ceramic powder 1 has a particle size sufficiently small to retain the suspended particles of a slip and also to provide shape retention when compacted.
The mold for slip-casting is provided by shaping and compacting the powder 1 to form a cavity 3 corresponding in shape to that of the desired article. This is facilitated by introducing a suitable forming device, having a configuration similar to that of the desired casting, into the powder. The shaping and compacting device 4, as shown in FIG. 1, has a lower portion 5, which forms the cavity 3, and an upper portion 6, which compacts the powder around the cavity 3, when the device 4 is pressed into the powder 1.
After the device is withdrawn from the powder, a slip suspension is introduced into the cavity and retained for a time sufficient to form the desired casting thickness, as in conventional slip-casting practice. The remaining slip is then removed and the casting allowed to dry at least partially before separating from the mold powder.
Compacting and shaping of the powder may be achieved by various methods, in separate steps or at the same time. The operation can be performed, for example, by introducing a forming device into the powder and subsequently compacting the powder around it. With an apparatus as shown in FIG. 1, shaping and compacting takes place in the same operation. Compacting may be achieved by pressing the device into the powder and/or with the use of vibrating means.
The procedure for separating the casting from the powder mold will depend on the fragility of the casting, i.e. its thickness and hardness. A relatively thick, short casting that has been allowed to dry fully may be merely pulled from the mold. However, for a thin or long casting, or one that has not completely dried, it may be necessary to remove or loosen the compacted powder from around the article before withdrawing it. Freeing of the casting from the compacted powder may be facilitated by an arrangement whereby the confining walls of the container are removed or separated from the powder.
After removal from the powder mold the casting can be fired in the conventional manner.
In order to be operative as a mold, the ceramic powder particle size must be sufficiently small so that the suspended particles of the slip introduced into the mold cavity are retained by the powder. Also, the powder must be capable of retaining the shape of the mold cavity when compacted. It has been found that a powder which has a sufficiently small particle size to retain the suspended particles can also be made to retain shape. In the case of relatively large or very small particles which do not provide the desired degree of shape retention when dry, the shape retention properties can be enhanced by adding small amounts of liquid to the powder.
It appears that particle sizes ranging from about 0.1 μm to 1000 μm can be utilized as a mold in accordance with the present invention. The preferred range is from about 1 μm to 50 μm. Particle size within this range should not require a liquid binder to provide the required shape retention properties. Powder particle size less than about 1 μm is difficult to produce, and it appears that particle sizes less than about 0.1 μm may not be sufficiently permeable to be useful for slip-casting.
A liquid binder, if used, must be inert to, or compatible with, other materials used in the system. Specifically, it must not dissolve or react with the mold powder, or react with the slip. Preferrably, the binder liquid will be the same as the slip liquid. The liquid used in the system may for example be water or alcohol.
The term ceramic powder or material, as used herein, refers to any non-metallic material, which may be non-crystalline or crystalline. Metallic material is difficult to reduce to the required particle size. Preferrably, the ceramic material will be a metal oxide, for example, alumina.
For high purity of the casting, the mold powder could be composed of the same material as the slip particles.
EXAMPLE
Experiments were conducted for the fabrication of tubes of β-alumina using α-alumina powder as the mold material. The mold powder particles were ground to approximately 4 μm while the slip particles were ground to approximately 1 μm. Several liquids for the slip suspension were tried including water, alcohols, and ketones, and methanol provided the best results. It was found that additives, use in conventional slip casting to facilitate removal from the mold, tended to decrease the density of the finished product and because they were not necessary no additives were used. The optional solids content of the slip suspension was found to be just under 60% by weight, since at about 60% the viscosity increases abruptly. Tubes were cast using apparatus similar to that illustrated in the drawing. The mold was made by inserting a tube (4) into a container (2) containing the α-alumina powder (1) and compacting the powder around the tube and removing the tube leaving the cavity (3). The β-alumina slip was poured in and retained for about 1 minute to provide a tube thickness of about 1 cm. The excess suspension was poured out and the casting was allowed to dry. After drying the casting was removed by loosening or removing the mold powder from around it. The unfired castings had a density of about 60% of theoretical density. The optimum sintering conditions were found to be 1550° C. for 11/2-2 hours providing a density of 98% of theoretical.
Tubes up to 50 cm. in length, from 1 to 50 mm in diameter, and from 0.1 mm to 5 mm in wall thickness were also fabricated in a similar manner. It was found that the mold powder can be reused repeatedly after drying without any adverse effects.
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A slip-casting system utilizing a ceramic powder for the mold. The system facilitates casting thin-walled and/or long objects without additives for demolding.
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