The present invention involves a method of processing polyacrylonitrile into a predetermined form. The first step in this method includes preparing a solution of a room temperature solvent that will dissolve polyacrylonitrile at room temperature and, a room temperature non-solvent that will not dissolve polyacrylonitrile at room temperature. The solution is prepared with sufficient non-solvent to render the room temperature solvent inoperable such that it will not dissolve polyacrylonitrile at room temperature and such that it will be operable at temperatures above 65xc2x0 C. to dissolve polyacrylonitrile therein. The second step in the present invention method involves combining polyacrylonitrile with the solution to form a mixture, in an amount of at least 20%, by weight, of polyacrylonitrile, based on the total weight of the mixture. Preferred is about 20% to about 50% by weight of the polyacrylonitrile. The third step involves processing the mixture in a hot-melt processor at temperatures in excess of 65xc2x0 C. to produce a polyacrylonitrile product. An optional fourth step, which would be useful in forming medical devices and related products, involves extracting solvent from the product by liquid extraction, e.g. warm water wash.

1. Field of the Invention
The present invention relates to a method of processing polyacrylonitrile (xe2x80x9cPANxe2x80x9d). More specifically, it relates to a method of processing PAN into products using significantly less solvent while creating products having superior physical characteristics. The present invention also relates to methods of processing polyacrylonitrile to produce prosthetic products and artificial joints, as well as the products themselves.
2. Information Disclosure Statement
The following patents are representative of the art relating to processing of polyacrylonitrile and products resulting therefrom:
U.S. Pat. No. 4,369,294 discloses block copolymers having acrylonitrile sequences and sequences of glutarimide units of a molecular weight of from about 10,000 to about 2,000,000 where the acrylonitrile sequences and sequences including glutarimide units are of molecular weight of at least about 400 with the number of sequences being at least about 2 and preferably 5 and higher.
U.S. Pat. No. 4,731,078 describes an artificial intraocular lens that features an optical body for refracting images onto the retina and an outer surface that encloses that optical body, is exposed to fluid within the eye, and has a refractive index no greater than 1.40. In another aspect, the optical body includes an internal refractive surface whose contour can be selectively changed to change its refractive power.
U.S. Pat. No. 4,731,079 describes a novel intraocular lens and mode of insertion therefore. The lens is of conventional shape and dimensions but is made of polymeric material having a softening point in the range of body temperature. The lens, prior to insertion is dimensionally reduced to enable introduction through a small incision by compression or by axial extension. The deformed lens is frozen in this configuration by cooling the lens below its softening temperature. The cooled, deformed lens is then inserted into the eye. The action of body heat, optionally supplemented by various non-harmful methods, permits the lens to regain its original configuration within the eye.
U.S. Pat. No. 4,943,618 describes a method that is disclosed for preparing polyacrylonitrile copolymers by heterogeneous reaction of polyacrylonitrile aquagel. Generally, the method includes the steps of preparing a solution of polyacrylonitrile by dissolving the polyacrylonitrile in a water-miscible solvent which is capable of dissolving the polyacrylonitrile but incapable of hydrolyzing the nitrile groups of the polyacrylonitrile under the dissolution conditions. Coagulating the polyacrylonitrile solution by replacing the solvent with a coagulating fluid such as water or a water miscible fluid incapable of dissolving polyacrylonitrile at temperatures below 80xc2x0 C., and incapable of reacting with nitrile groups of the polyacrylonitrile, thus obtaining the polymer in the aquagel state. Replacing the coagulating fluid with a fluid reagent capable of reacting with nitrile groups of the polyacrylonitrile aquagel but incapable of dissolving the polyacrylonitrile aquagel at the selected reaction temperature. Allowing the fluid reagent to chemically react with the nitrile groups of the aquagel while the polyacrylonitrile aquagel is undissolved to form a copolymer product. The copolymer product is then either used in further chemical reactions involving newly formed and/or original side substituents, or isolated and utilized for molding or shaping into various articles. Various plasticizers, which when undiluted are capable of dissolving polyacrylonitrile, may be added to the copolymer product to assist in molding or shaping the material into an article.
U.S. Pat. No. 5,149,052 describes a method and apparatus for precision molding soluble polymers is disclosed, in order to form an exact and precisely shaped product, such as contact lenses and surgical implants. A preferred mold for forming contact lenses includes a female part having an indentation and a sharp circumferential edge surrounding the indentation. The mold also includes a male part which is adapted to contact the sharp circumferential edge of the female part to form the molding cavity between the indentation of the female part and the male part. A semi-permeable gate is formed between the female part and the male part for introducing coagulating fluid into the molding cavity while preventing the escape of the polymer solution from the molding cavity. The semi-permeable gate allows the diffusion of the coagulating fluid into the molding cavity at a faster rate than the rate of diffusion of solvent out of the molding cavity. The polymer solution is coagulated by the influx of the coagulating fluid into the polymer solution which causes both the coagulation and swelling of the polymer solution. Swelling of the polymer solution coagulates the solution under pressure within the molding cavity to form a precisely shaped product. Coagulation proceeds under pressure since the solvent diffuses out of the semi-permeable gate at a slower rate than the diffusion of the coagulating fluid into the molding cavity.
U.S. Pat. No. 5,159,360 describes a contact lens that is a soft, disposable lens which, under eye wearer conditions, changes one or more characteristics essential for comfortable use, at a predetermined time to initiate disposal thereof by the user. This lens, under wear conditions, changes, for example, at least its base curve redius and its deformability as a consequence of a change in hydrophilicity of at least a portion of the contact lens material. This hydrophilicity change may be achieved by various means, e.g. degradation of crosslinking bridges or conversion of less hydrophilic groups to groups having greater hydrophilicity. In one preferred embodiment, the conversion is achieved by hydrolysis of selected functional (hydrophobic) groups into hydrophilic groups.
U.S. Pat. No. 5,217,026 describes a guidewire that involves an elongated, non-hydrogel core element forming an inner part of the device, and an integral outside tubular layer of elastomeric hydrogel (xe2x80x9chydrogel sleevexe2x80x9d). This outer hydrogel layer has unique physical characteristics. They are (a) Gradient of chemical composition with increasing concentration of polar groups in the outward direction away from the core element; (b) Gradient of swelling in contact with water with water content increasing in the outward direction away from the core element; (c) Compressive stress in the outer hydrophilic layer causing the hydrogel in that layer to swell to a water content and, optionally, (d) Inward-directed radial stress pushing the outside hydrogel layer constantly against the inner core element. The present invention also involves the methods of making these guidewires, including melt extrusion directly onto the core element, coagulation from solution, in situ hydrogel polymer formation, and tubing extrusion followed by consequent shrink-fit over the core.
U.S. Pat. No. 5,218,039 describes stable emulsions and dispersions of both the water-in-oil and oil-in-water types that are prepared by subjecting mixtures of the two phases to shear stress in the presence of nitrile group-containing copolymers capable of forming hydrogels containing at least 90%, by weight, of water at room temperature.
U.S. Pat. No. 5,368,048 describes a method of making a radio-opaque tipped, sleeved guidewire. It includes providing a bendable core piece of a predetermined length, having a control end and having a predetermined core diameter, and providing a shrinkable polymeric sleeve formed of a first polymer composition having a first diameter at least as large as said core diameter and having a second, smaller diameter from shrinking said second diameter, which is less than said core diameter. The polymeric sleeve is placed over the core piece while the polymeric sleeve has its first diameter, so as to have one end of the polymeric sleeve cover at least a portion of the distal end of the core piece. Next, a mixture of a radio-opaque metal powder and a second polymer composition is provided. The second polymer composition is capable of forming a physical bond with the first polymeric composition of the polymeric sleeve. The mixture is inserted into the overhanging polymeric sleeve at the distal end of the core piece and the polymeric sleeve is shrunk to its second, smaller diameter. The physical bond is formed between the first polymer composition and the second polymer composition. The present invention is also directed to the resulting guidewire products.
The following patents are representative of artificial joint patents:
U.S. Pat. No. 4,944,758 describes an artificial joint comprising a first member including a butt portion located at one end of the first member and having an internal opening and a long guide groove extending to the opening and a second member in contact with the butt portion of the first member and including an expanded portion at one end of the second member. The expanded portion is fitted in the internal opening of the first member. A projection along both sides of the long guide groove prevents the expanded portion from separating from the internal opening except at prescribed positions of the first and second members, the long guide groove guides the movement of the second member as it bends relative to the first member in a prescribed direction.
U.S. Pat. No. 5,092,896 describes a finger joint prosthesis that is provided which consists of two pegs of sintered hydroxylapatite for anchoring in adjacent finger bones and which is provided with an intermediate slide layer of polyurethane between the pegs to permit relative movement therebetween. The pegs together with the intermediate layer which may be anchored on one of the pegs form concave and convex bearing areas mating with each other to allow a guided motion in the bend-stretch plane.
U.S. Pat. No. 5,425,777 describes a metallic implantable finger joint that has a biocompatible protective coating and includes both a base member and a protraction member. The base member is formed with a recess and has a protrusion projecting from inside the recess. The protraction member has a hemispherical surface which is slidingly engageable with the recess of the base member. Additionally, the protraction member is formed with a groove which engagingly receives the protrusion from the base member. This engagement is such that when the base member is juxtaposed with the protraction member, the interaction between the protrusion and the groove allows for relative movement between the members in flexion-extension, lateral rotation and pure rotation. The finger joint can also include implant barbs which are selectively engageable with the base member and the protraction member.
U.S. Pat. No. 5,549,690 describes a method for molding a prosthetic CMC thumb joint, and the joint manufactured therefrom, involves anatomically locating the two non-perpendicular and non-intersecting axes of rotation for the joint. The surface of revolution about these two axes, which is a torus, is then used to mathematically model the bearing surfaces of the prosthetic joint.
U.S. Pat. No. 5,728,157 describes a non-resorbable flexible prosthesis that includes a composite made of an elastomeric matrix and a plurality of hydroxylapatite particles dispersed throughout the matrix. The hydroxylapatite particles form about 25%-70%, by weight, of the prosthesis. The matrix is cured to form a flexible prosthesis such that an applied force can distort the flexible prosthesis from its original shape and the flexible prosthesis will substantially return to its original shape when the applied force is removed.
U.S. Pat. No. 5,578,086 describes a non-percutaneous prosthesis, reconstuctive sheeting and composite material which exhibit excellent tissue adhesion, outstanding biocompatibility, moldability, trimability and flexibility are disclosed. The non-percutaneous prosthesis, reconstructive sheeting and composite material can be easily molded into various shapes, trimmed with a scalpel and deformed during prosthesis positioning. The non-percutaneous prosthesis comprises a biocompatible composite material which is made of an elastomeric material and bio-active ceramic or glass particles and has a predetermined shape. The bio-active ceramic or glass particles are dispersed throughout a matrix of the elastomeric material having a predetermined shape, or the elastomeric material is formed to the predetermined shape and the bio-active ceramic or glass particles are coated on a surface of the elastomeric material. In another embodiment, the non-percutaneous prosthesis comprises a base material of predetermined shape and a layer of elastomeric material provided on the base material, wherein a layer of elastomeric material has distributed therein or provided thereon bio-active ceramic or glass particles. The elastomeric material is preferably one of silicone, polyurethane and its derivatives, hydrogel and C-Flex(copyright) and, more preferably, is silicone or hydrogel. The bio-active ceramic or glass particles are preferably made of hydoxylapatite. The reconstructive sheeting comprises a biocompatible composite material made of an elastomeric material and bio-active ceramic or glass particles. Also, the present invention provides a biocompatible composite material comprising hydrogel and particles of a bio-active ceramic or glass material. The particles are preferably dispersed throughout a matrix of hydrogel.
U.S. Pat. No. 6,168,626 describes an ultra high molecular weight polyethylene molded article for artificial joints that has molecular orientation or crystal orientation in the molded article, and is low in friction and is superior in abrasion resistance, and therefore is available as components, for artificial joints. Further, the ultra high molecular weight polyethylene molded article for artificial joints can be used as a component for artificial hip joints (artificial acetabular cup), a component for artificial knee joints (artificial tibial insert) and the socket for artificial elbow joints, and in addition to the medical use, it can be applied as materials for various industries by utilizing the characteristics such as low friction and superior abrasion resistance.
U.S. Pat. No. 6,383,223 describes, in an endoprosthesis for a joint, the two interacting joint parts are joined by a cord-type connection piece, which is attached in the vicinity of the body axis of the convex condyle and extends through a longitude groove in the flexion direction of the joint. The connection piece assures a play space between the contact surfaces of joint. It is protected from friction on groove wall by an elevation in concave joint part. An elevation at concave joint part and a depression at convex joint part interact in such a way that the lateral movement play space between depression and elevation determines the freedom of movement with respect to the lateroflexion of the joint. In preferred forms of embodiment, thanks to spherical surfaces at least one pair of corresponding sliding surfaces on the two condyles lie flatly on one another, under load, in any position of the joint.
U.S. Pat. No. 6,386,877 describes the implant that has an anchoring part with an axis, a general cylindrical section and a peripheral surface. The latter is provided, in the generally cylindrical section, with protuberances which are distributed around the axis. At least the majority of these protuberances are elongate and parallel with the axis and have at least one terminal surface which is contiguous with a recess having a base formed by the peripheral surface. In this way, the anchoring part can be pushed into a substantially cylindrical hole in a one such that the implant is immediately anchored in the bone in a stable manner, said implant nevertheless having a high degree of strength.
U.S. Pat. Application Publication No. 2001/0025199 describes the invention that shows an artificial finger joint comprising a convex joint head and comprising a concave joint shell which can be fastened independently of one another with a respective shaft in a bone end and which can be moved in an articulation plane from an extension position with parallel shaft axes into a hyperextension position or into an articulation end position. A guide pin projects out of the joint shell in the direction of its shaft axis and protrudes into a pocket of the joint head with the pocket having a first abutment for the guide pin in the hyperextension position. A second abutment between the joint shell and the joint head prevents a tilting of the guide pin and shaft of the joint shell about the first abutment in the hyperextension position.
Notwithstanding the prior art, the present invention is neither taught nor rendered obvious thereby.
The present invention involves a method of processing polyacrylonitrile into a predetermined form. The first step in this method includes preparing a solution of a room temperature solvent that will dissolve polyacrylonitrile at room temperature and, a room temperature non-solvent that will not dissolve polyacrylonitrile at room temperature. The solution is prepared with sufficient non-solvent to render the room temperature solvent inoperable such that it will not dissolve polyacrylonitrile at room temperature and such that it will be operable at temperatures above 65xc2x0 C. to dissolve polyacrylonitrile therein. The second step in the present invention method involves combining polyacrylonitrile with the solution to form a mixture, in an amount of at least 20%, by weight, of polyacrylonitrile, based on the total weight of the mixture. Preferred is about 20% to about 50% by weight of the polyacrylonitrile. The third step involves processing the mixture in a hot-melt processor at temperatures in excess of 65xc2x0 C. to produce a polyacrylonitrile product.
An optional fourth step, which would be useful in forming medical devices and related products, involves extracting solvent from the product by liquid extraction, e.g. warm water wash.
The room temperature solvent is selected from any solvent strong or weak, that will dissolve PAN at room temperature, these include dimethyl sulfoxide, dimethyl formamide, NaSCN, Ca(CNS)2, nitric acid, ethylene carbonate and mixtures thereof, although others may be used. The present invention process non-solvent may be any which function to render the room temperature solvent useless as a solvent for PAN at room temperature, but will permit that solvent to function at elevated temperatures. The non-solvent may be selected from the group consisting of water, liquid carbon compounds that do not dissolve polyacrylonitrile, and combinations thereof. The carbon compounds may be selected from the group consisting of liquid straight chain hydrocarbons, liquid ring hydrocarbons, liquid ring-straight chain hydrocarbons, and mixtures thereof. The non-solvent may also be selected from the group consisting of glycol, liquid alcohols, liquid ketones, and combinations thereof. In general, the solvent solution is achieved by simply mixing the solvent and non-solvent, at room or elevated temperature, and the components should be miscible with one another.
The solution preferably contains about 40% to 98% of the room temperature solvent and about 60% to 2% of the room temperature non-solvent, by weight, based on the weight of the room temperature solvent and the room temperature non-solvent. More preferably, the solution contains at least 50%, by weight, of room temperature solvent, based on the weight of the room temperature solvent and the room temperature non-solvent.
The mixture processing step following the mixing of the solution and the polyacrylonitrile could involve cold molding or casting or the like, but is preferably and advantageously a processing step in a hot-melt processor, such as extrusion, injection molding, compression molding and hot casting.
In preferred embodiments of the present invention, the step (b) PAN is granular (i.e. powder) polyacrylonitrile, and the resulting mixture of the process is in flake form.


A method and equipment for mixing hard granules into tire tread bodies and into sundry rubber strips and tread stock. Rubber stock is extruded into tread bands of a suitable shape which are rolled under control, in a suitable thickness and number of layers, in a circular process over a pre-treated tire, or other object. The tire is subsequently patterned and vulcanized. The hard granules are distributed according to a predetermined configuration onto at least part of the surface of the extruded rubber tread band before the next layer is rolled in a circular process onto the pre-treated tire, using dedicated equipment so that the granules will be mixed into the patterned wearing surface of the tire after profiling and vulcanization.

The invention concerns a method and equipment for mixing hard granules into tyre tread bodies and furthermore into sundry rubber strips and tread stock, whereby rubber stock is extruded into tread bands of a suitable shape which are rolled under control, in a suitable thickness and number of layers, in a circular process over a pre-treated tyre or other material (object) which is subsequently patterned and vulcanised.
Vehicle tyres consist, broadly speaking, of a fibre-reinforced carcass (bound with wire or rope) which forms the inner layer of the tyre, and an outer wearing layer which is made of vulcanised rubber or comparable material and is profiled into a pattern over the reinforced tyre carcass.
Tyres are manufactured according to the above specification but retreading of them is also a familiar process. When the pattern of the wearing surface (the tread) has worn down so far that is ceases to serve its function, the remainder of the wearing surface is buffed and a new tread is placed over the fibre-reinforced carcass. One way in which this is done is by overlaying the circular process of the tyre carcass with an extruded rubber tread band of a suitable thickness, which is then profiled into a new pattern and vulcanised.
The role of the outer layer of the tyre is to form a resistant and wearing surface against the surface on which the vehicle is driven. Many methods are known for increasing tyre resistance and reducing skidding of vehicles on a slippery surface such as ice or snow. Particular mention should be made of spikes which are driven into the tyres after conventional manufacture, and snow chains.
In recent years and decades, ideas have been proposed for mixing and/or anchoring of various types of material into or onto the wearing surface of tyres.
Methods are known for mixing hard granules into the tread body of a tyre in order to increase its resistance on a slippery surface, in particular snow and ice. The U.S. Pat. No. 2,672,910 from 1948 describes the production of a tyre in which coated hard granules are mixed with the raw rubber which is used for production of the tyre. By coating the granules improved bondage is obtained with the rubber body.
Furthermore, methods have been developed for re-treading. A worn tyre is pre-treated (buffed) to prepare the rolling of a new tread body onto it. A new layer of rubber is wrapped around the circular process of the tyre and then profiled into a pattern, cf. German Patent DE 4.025459 A1, which concerns general re-treading of used tyres.
European Patent Applications EP 0 454.025 A1 and EP 442.155 A1 furthermore describe methods for production of tyres and/or re-treading, whereby coated hard granules are mixed into the raw rubber before extrusion and rolling on the pre-treated tyre.
The above patents describe methods and equipment for production of treads and tyres. They describe the mixing of hard granules into the tread body of the tyres in order to increase the tyre""s resistance against the driving surface and to reduce vehicle sliding on ice or snow.
None of the aforementioned methods or equipment for mixing hard granules has achieved widespread acceptance, as a result of shortcomings of these methods in the production process.
The disadvantage of these methods has been the cost involved in mixing the hard granules into the rubber body before extrusion, for reasons including substantial wear and tear to the equipment.
The required amount of hard granules must be considered excessive if they are mixed with the entire raw material body. Nor has it proved possible to control the final location of the hard granules in the wearing surface of the tyre, which must also be considered a disadvantage.
Yet another disadvantage is the inadequate bondage yielded between the fibre-reinforced carcass and the granulated tread body, since the granules show a tendency to impair the bondage between the carcass and the wearing surface. Furthermore, mixing granules into the entire rubber body is considered to reduce the flexibility of the tyre carcass.
The aim of the invention is to present a method and equipment which are at once straightforward in use and production, and economical to operate, and which also enable control to be maintained over the mixing and location of hard granules in the wearing surface of tyres. One of the major advantages of the method for which the patent is being applied is that it does not require extra labour for re-treading of tyres.
By manufacturing tyres and other treads with a mixture of hard granules, the following aims are achieved:
Increased vehicle resistance to slippery surfaces.
Reduced road wear compared with the use of spiked tyres.
Enhanced general driving properties compared with the use of spiked tyres or snow chains.
These properties have been confirmed in tests by VTI of Sweden (Swedish Public Roads Administration) and BAST of Germany (German Public Roads Administration or Bundesanstalt fxc3xcr Stassenwesen).
These aims are achieved by the invention""s distinctive feature of distributing the hard granules according to a predetermined configuration onto at least part of the surface of the extruded rubber tread band before the next layer is rolled in a circular process onto the pre-treated tyre, using dedicated equipment so that the granules will be mixed into the patterned wearing surface of the tyre after profiling and vulcanisation.
A further distinctive feature of the invention is that the hard granules are distributed according to a predetermined configuration onto at least part of the surface of the extruded rubber tread band, thereby allowing the extent to which the tread band is covered with hard granules to be controlled, and likewise the distribution of the granules into predetermined parts of the patterned and vulcanised tyre.
A further distinctive feature of the invention is that 0.01 to 0.1 gm of hard granules are distributed onto each square centimeter of rubber tread band which is covered with hard granules, with each granule of the diameter range 1-3 mm, particularly 1.5-2.0 mm.
Furthermore, a distinctive feature of the invention is that the hard granules are distributed according to a predetermined configuration onto the part of the surface of the extruded rubber tread band which, after rolling onto the pre-treated tyre carcass surface, forms the outer surface of the vulcanised and patterned tyre, and that the granule distribution equipment is located after the extruder in the production process and above the extruded rubber tread band, and in front of the tyre, and that the granules are distributed onto the rubber tread band before it is rolled on to the tyre.
The equipment is unique insofar as it consists of a funnel into which the hard granules are fed before distribution, and a feeder (revolving rubber-clad cylinder which feeds a suitable quantity of granules from the funnel onto a track for controlling their delivery onto the rubber tread band, and the distribution device (the track) can be adjusted to control the direction and speed at which the granules are delivered onto the extruded rubber tread band and match as closely as possible the direction and speed of the band itself, and the quantity of granules fed and distributed from the funnel is controlled by a feeder door and by the speed of the cylinder, thereby controlling that the granules are located on the tread band at a suitable density.
Much research has been conducted into the properties of tyres which are produced using the new method described above. Very thorough testing by BAST of Germany has convincingly demonstrated that road wear caused by tyres with mixed hard granules is greater than that caused by xe2x80x9cwinter tyresxe2x80x9d but considerably less than the average road wear caused by 9 types of spiked tyre. Tests at BAST revealed that, setting road wear caused by nailed tyres at a reference point of 100%, wear caused by the above-mentioned hard-granule tyres measures 7% and that caused by winter tyres 2%.
Tests conducted by the Swedish Public Roads Administration of Linkoping show that hard-granule tyres clearly displayed much better road-holding properties under slippery conditions than the same type of tyre without hard granules. The tests also showed that hard-granule tyres generally display better road-holding properties than spiked tyres when rolling along the road surface. This is a particular advantage, for example, on bends and where anti-braking systems prevent the wheels from locking completely.
In all likelihood, many types of hard granules may be used for mixing. The trials which have been made have used granules of SiC (silicon carbide, xe2x80x9ccarborundumxe2x80x9d) and Al2O3 (aluminium oxide), which have been coated with familiar bonding materials and/or adhesives.

Method and equipment for mixing hard granules for tire treads


A flat-hose assembly has a proximal end and a distal end adapted for use with a negative pressure wound drainage system. The flat-hose assembly comprises a top layer, a bottom layer, and a filter layer. The bottom layer forms an opening at the distal end of the flat-hose assembly to allow exudates of a wound to flow into the flat-hose assembly. The filter layer is disposed between the top layer and the bottom layer. The top and bottom layer form a seal area along a periphery of the top layer and the bottom layer to seal the filter layer therebetween.

Negative pressure, also referred to as suction, has proven to be a successful technique for the healing of wounds. Negative pressure is applied by a vacuum source through tubing that is attached to a dressing that covers a wound and healthy skin beyond the wound perimeter. Present systems typically use commercially available round tubing made of various materials such as, PVC, nylon, urethane, or similar polymeric materials. One end of the tubing is connected to the vacuum source and a collection device is located between the vacuum source and the wound. A second end of the tubing passes through the dressing in order to evacuate exudates from the wound and place the exudates into the collection device. An airtight seal needs to be maintained between the healthy skin and the dressing as well as between the tubing and the dressing.
Several disadvantages exist with the existing systems. First, it is difficult to make an airtight seal between the dressing and the tubing. If the seal is not airtight, the vacuum will be lost and no exudates will be removed from the wound. Second, the round tubing at the wound site often creates pressure points on the patient as the patient moves around. The round tubing may end up underneath the patient, causing wounds or other patient discomfort. A third disadvantage to the currently available systems is that it is easy to cause the tubing to be bent or kinked, blocking the flow of exudates and inhibiting the application of negative pressure. Thus, a need exists for a hose assembly for a negative pressure wound treatment system that maintains a better seal with a wound dressing, is not as susceptible to blocking the flow through the tubing by kinking, and is less likely to cause patient discomfort or further pressure points.

Flat-hose assembly for wound drainage system


An endoscope has a distal objective and proximal devices for image viewing including a fiber optical image guide, which extends within the endoscope between the objective and the devices for viewing the image and one of whose end regions is fixedly mounted on the endoscope and the other end region of which is axially movably mounted, and the image guide is secured in its proximal end region and the remaining distal end region of the image guide is freely movable, the objective also being movably received relative to the endoscope and the distal end of the image guide and the objective being connected together for common axial movement.

This invention relates to an endoscope
Endoscopes (also referred to as endoscopic optical systems) of the type to which the invention relates generally have a proximal main body, distally connected to which there is a tubular shaft region. In such devices, e.g. ureterscopes, the shaft region is of rigid construction and has a relatively small diameter in comparison to its length. Fibrous light guides can be positioned in the tubular shaft region, also termed cover tube or optical tube, which extend from a proximal entry point in the vicinity of the main body to the distal end of the optical tube, and serve to illuminate the field to be observed. Furthermore, the optical tube accommodates the actual devices for transmitting the image, optionally in a further tube (system tube).
The image transmission occurs between a lens provided in the distal end region of the system tube and a proximal device for image viewing, e.g., an eyepiece or a video camera, etc.
Particularly in endoscopes with a small diameter, a so-called fiber optic image guide is used for transmission. The image guide extends between the distal lens and the proximal image viewing devices. Such a fiber optic image guide comprises a plurality of longitudinally extending fibers of transparent material, particularly of materials based on glass, e.g., quartz glass.
A substantial problem with conventional endoscopes in this connection is that the used image guides of, e.g., quartz glass have different expansion characteristics from the surrounding regions of the endoscope, e.g., the system tube, which comprises metal.
In particular, a rigid endoscope of small diameter, e.g., a ureterscope, must be able to withstand bending of its shaft region during use. The image guide is generally not centrally disposed so that bending of the endoscope results in stretching or buckling which can be accommodated by the metallic system tube without great problems but can be accommodated only to a limited extent by a fixed xe2x80x9cglass fiberxe2x80x9d image guide positioned therein. Similar problems occur when heat sterilizing endoscopes with fiber optic image guides. The image guide and endoscope expand to different extents and at different speeds from each other and stresses can thus occur, particularly if both ends of the image guide are fixed.
There are various possibilities for dealing with the above problems. In this connection, e.g., WO 9605764 discloses an endoscope of the type referred to above in which the image guide is fastened in the system tube only at its distal end. The proximal end, on the other hand, is movably received in the main body. A disadvantage with this known construction is that, particularly having regard to the very short focal lengths of the optical components which are used, a correction must be effected each time the proximal end of the image guide moves, which necessitates a relatively large construction expense.
It is thus an object of the invention, starting from the prior art, to provide an endoscope in which the occurrence of stresses between the image guide and endoscope can be prevented at low constructional expense.
In the endoscope in accordance with the invention it is provided that the image guide is fixedly secured in the endoscope substantially only at its proximal end region while the remaining image guide region to its distal end is mounted to be freely movable in the axial direction.
In conventional devices, which have a main body and a shaft attached thereto, the fastening of the image guide is effected, e.g., in the region of the main body while its region situated within the shaft is not fixed. Potential thermal influences or bending, which result in differential elongation of the image guide and the surrounding endoscope, can thus be compensated for without difficulty, the distal end of the image guide moving in the axial direction with respect to the endoscope. In order to make constant optical imaging quality possible, the invention further provides that the objective is also mounted movably with respect to the endoscope and is so connected to the distal end of the image guide that common movement occurs with a constant spacing.
The term xe2x80x9cobjectivexe2x80x9d means any and all optical devices which make imaging of the field of view at the distal end of the image guide possible. It can be a lens or lens system, wherein the connection between the image guide and objective can be effected, e.g., by adhesive. Other types of connection are, however, also possible.
The invention is preferably implemented in a rigid endoscope of small diameter, i.e., an endoscope which has a main body, from which a rigid, relatively long shaft region of small diameter extends. Such an endoscope can be bent within limits during use, whereby the relative movement described above between the image guide and endoscope occurs which is compensated for in a particularly simple manner in devices in accordance with the invention.
The proximal end of the image guide is generally fixedly mounted in the main body of the endoscope. For this purpose, an appropriate fastening device, for instance, can be provided in the main body which holds the proximal end of the image guide at a constant distance from the image viewing devices. The remaining region of the image guide is held freely axially movable up to its distal end, the distally provided objective being axially movably mounted with respect to the endoscope and connected to the distal end of the image guide.
It would be possible, e.g., for the objective to be a single, e.g., gradient lens which is secured by adhesive to the distal end of the image guide. A further advantageous embodiment of the invention provides that the objective is accommodated in an objective tube which is mounted to be axially movable with respect to the endoscope or the surrounding system tube. The distal end of the image guide is connected by adhesive or the like to the proximal end of the objective tube or to the proximal lens of the objective. This embodiment may be realized in a particularly simple manner, particularly if the objective comprises a number of lenses, and allows simultaneous tolerance-free movement of the light guide and objective.
It can be provided in a further advantageous embodiment that the objective tube or the objective is received in the endoscope secured against rotation. This can be achieved, e.g., by providing an elongated projection on the objective tube which engages in a suitable groove in the system tube.
The advantages of the invention reside substantially in the particularly simple constructional implementation with which an optimum optical imaging quality is always ensured, even under widely varying operational conditions. Due to the fact that the distal objective is axially movably accommodated in the endoscope and is automatically appropriately moved axially in the event of potential, e.g., thermally induced, changes in length of the image guide while maintaining the optical conditions, particularly simple adjustment is possible.


In a thermoelectric generator or Peltier arrangement having a thermoelectrically active semiconductor material constituted by a plurality of metals or metal oxides the thermoelectrically active material is selected from a p- or n-doped semiconductor material constituted by a ternary compound of the general formula (I)

The invention relates to thermoelectrically active materials, as well as to generators and Peltier arrangements containing them.
Thermoelectric generators per se have been known for a long time. p- or n-doped semiconductors, which are heated on one side and are cooled on the other side, transport electrical charges through an external circuit, with electrical work being done at a load in the circuit. The efficiency achieved in this case for the conversion of heat into electrical energy is limited thermodynamically by the Carnot efficiency. For instance, with a temperature of 1000 K on the hot side and 400 K on the xe2x80x9ccoldxe2x80x9d side, an efficiency of (1000-400): 1000=60% would be possible. Unfortunately, efficiencies of only up to 10% have been achieved to date.
On the other hand, if a direct current is applied to such an arrangement, then heat will be transported from one side to the other. Such a Peltier arrangement works as a heat pump and is therefore suitable for the cooling of equipment parts, vehicles or buildings. Heating by means of the Peltier principle is also more favorable than conventional heating, because the quantity of heat transported is always greater than corresponds to the energy equivalent which is supplied.
A good review of effects and materials is given e.g. by Cronin B. Vining, ITS Short Course on Thermoelectricity, Nov. 8, 1993, Yokahama, Japan.
Thermoelectric generators are currently used in space probes for the generation of direct currents, for the cathodic corrosion protection of pipelines, for the energy supply of lighted and radio buoys, and for the operation of radios and television sets. The advantages of thermoelectric generators are that they are extremely reliable, they work irrespective of atmospheric conditions such as humidity, and no material transport susceptible to disruption takes place, instead only charge transport; the fuel is burned continuouslyxe2x80x94and catalytically without a free flamexe2x80x94so that minor amounts of CO, NOx and unburned fuel are released; it is possible to use any fuels from water through natural gas, gasoline, kerosene and diesel to biologically produced fuels such as rapeseed oil methyl ester.
Thermoelectric energy conversion therefore fits in extremely flexibly with future requirements such as hydrogen economy or energy production from regenerative energies.
An especially attractive application could involve use for conversion into electrical energy in electrically powered vehicles. No modification to the existing network of the fuelling stations would need to be carried out. For such an application, however, efficiencies in excess of 30% would be necessary.
The conversion of solar energy directly into electrical energy could also be very attractive. Concentrators such as parabolic collectors can focus the sun""s energy with efficiencies of 95-97% onto thermoelectric generators, so that electrical energy can be produced.
Higher efficiencies, however, are necessary for use as a heat pump.
It is an object of the present invention to provide thermoelectric active materials which permit higher efficiencies than previously. A characteristic of thermoelectric materials is the so-called Z factor (figure of merit)   Z  =                    α        2            *      σ        K
with xcex1 being the Seebeck coefficient, "sgr" being the electrical conductivity and K being the thermal conductivity.
A more accurate analysis is the efficiency as xcex7  η  =                              T          high                -                  T          low                            T        high              *                  M        -        1                    M        +                              T            high                                T            low
with M=[1+z/2(Thighxe2x88x92Tlow)1/2
(cf. Mat Sci. and Eng. B29 (1995) 228).
The aim is therefore to provide a material having a maximally high value for Z and high achievable temperature difference. In terms of solid-state physics, many problems need to be overcome in this case:
A high xcex1 entails high electron mobility in the material; i.e. electrons (or holes in the case of p-conducting materials) must not be strongly bound to the atom rumps. Materials having a high electrical conductivity usually also have a high thermal conductivity (Wiedemann-Franz law), so that Z cannot be favorably influenced. Currently used materials such as Bi2Te3, PbTe or SiGe indeed represent compromises. For instance, the electrical conductivity is reduced less than the thermal conductivity by alloying. It is therefore preferable to use alloys such as e.g.(Bi2Te3)90(Sb2Te3)5(Sb2Se3)5 or Bi12Sb23Te65, as are described in U.S. Pat. No. 5,448,109.
For thermoelectric materials with high efficiency, it is also preferable to satisfy further constraints. Above all, they must be thermally stable so that they can work for years without substantial loss of efficiency at working temperatures of 1000 to 1500 K. This entails phases which per se are stable at high temperatures, a stable phase composition, as well as negligible diffusion of alloy constituents into the adjoining contact materials.
The recent patent literature contains descriptions of thermoelectric materials, for example U.S. Pat. No. 6,225,550 and EP-A-1 102 334. U.S. Pat. No. 6,225,550 relates essentially to materials constituted by MgxSbz, which are additionally doped with a further element, preferably a transition metal.
EP-A-1 102 334 discloses p- or n-doped semiconductor materials which represent an at least ternary material constituted by the material classes: silicides, borides, germanides, tellurides, sulfides and selenides, antimonides, plumbides and semiconducting oxides.
There is nevertheless still a need for thermoelectrically active materials which have a high efficiency and exhibit a suitable property profile for different application fields. Research in the field of thermoelectrically active materials can by no means yet be regarded as concluded, so that there is still a demand for different thermoelectric materials.
We have found that this object is achieved by a thermoelectric generator or a Peltier arrangement having a thermoelectrically active semiconductor material constituted by a plurality of metals or metal oxides, wherein the thermoelectrically active material is selected from a p- or n-doped semiconductor material constituted by a ternary compound of the general formula (I)
MexSAySBzxe2x80x83xe2x80x83(I)
with
Me=Al, Ti, Zr, V, Nb, Ta, Cr, Mo, W, Mn, Fe, Co, Ni, Cu or Ag,
SA,SB=B, C, Si, Ge, Sb, Se or Te,
where SA and SB respectively come from different groups of the periodic table,
x, y, z independently of one another have values from 0.01 to 1,
and where the proportion by weight of SA and SB together is no more than 30%, expressed in terms of the total semiconductor material,
except for ternary compounds constituted by AlB12 and SiB6,
or a mixed oxide of the general formula (II)                                           [                                                            (                  CaO                  )                                u                            ·                                                (                  SrO                  )                                v                            ·                                                (                  BaO                  )                                w                            ·                                                (                                                            1                      /                      2                                                                                Bi                      2                                                                                O                      3                                                        )                                x                                      ]                    f                ·                                            2                            n                        +            a                    2                ·                  (                                    {              k              }                                                  Me              n                                                                  O                                  n                  2                                            ·                              {                                  2                  -                  k                                }                                                                Me                              n                +                a                                                                O                                                n                  +                  a                                2                                              )                                    (        II        )
with
Me=Fe, Cu, V, Mn, Sn, Ti, Mo, W
n=integer from 1 to 6,
a=1 or 2,
f=number from 0.2 to 5,
k=number from 0.01 to 2, preferably 0.01 to 1.99, e.g. 1
u+v+w+x=1.
The thermoelectric generators and Peltier arrangements according to the invention enhance quite generally, on the one hand, the range of available thermoelectric generators and Peltier arrangements. Owing to the different chemical systems, it is possible to satisfy different requirements in various application fields of the thermoelectric generator or Peltier arrangements. The thermoelectric generators and Peltier arrangements according to the invention hence significantly extend the possibilities for application of these elements under different conditions.
Preferred semiconductor materials will be explained in more detail below.
In the ternary compounds of the general formula (I), SA and SB are preferably selected from B, C, Ge, Sb and Te.
In this semiconductor material, Me is preferably selected from one of the following groups:
1) Al, Ti, Zr.
2) V, Nb, Ta
3) Cr, Mo, W
4) Mn, Fe, Co, Ni
5) Cu, Ag.
The proportion of doping elements is up to 0.1 atom % in the alloy, or from 1018 to 1020 charge carriers per cubic centimeter. Higher charge-carrier concentrations cause disadvantageous recombinations, and hence a reduced charge mobility. The doping is carried out with elements which cause an electron surplus or deficit in the crystal lattice, e.g. with iodide for n-type semiconductors and alkaline-earth elements for p-type semiconductors, so long as a 3/5 or 3/6 semiconductor is present.
A further possible way of doping is obtained if holes or electrons are deliberately introduced into the materials by means of super- or sub-stoichiometric compositions, which obviates the need for an additional doping step.
Dopant elements may also, however, be introduced via aqueous solutions of metal salts, which are subsequently dried in the mixture. The metal cations are then reduced e.g. by hydrogen at elevated temperatures or remain in the material without reduction. Preferably, the p- or n-doping is carried out through selection of the quantitative proportions of the compounds, or the p-doping is carried with alkali metals and the n-doping with Sb, Bi, Se, Te, Br or I (see WO 92/13811).
The materials according to the invention of the general formula (I) are prepared by known methods, the element compounds e.g. by sintering the element powders at high temperatures, but below the melting point, under an inert gas such as argon or in a vacuum, or by melting in a high vacuum and subsequently powdering and sintering or by melting the mixture of element powders and cooling.
In the mixed oxides of the general formula (II), n denotes the oxidation state of the metal Me and f denotes a stoichiometric factor. f has a value in the range from 0.2 to 5, preferably 0.5 to 2, particularly preferably 1. a indicates the difference between the two different oxidation states of Me.
For the stoichiometric factor f, numbers from 0.2 to 0.99, the value 1, numbers from 1.01 to 2 and numbers from 2.01 to 5 may be indicated as preferred ranges. Each of these cases involves a preferred embodiment of the invention.
The expression in brackets   (            {      k      }                  Me      n                          O                  n          2                    ·              {                  2          -          k                }                        Me              n        +        a                        O                        n          +          a                2              )
may preferably be, specifically:
FeO//Fe2O3
Cu2O//CuO
VO//V2O3
V2O3//V2O5
VO2//V2O5
VO2//V2O3
MnO//Mn2O3
Mn2O3//Mn2O3
SnO//SnO2
TiO//Ti2O3
Ti2O3//TiO2
MoO2//MoO3 or
WO2//WO3, especially preferably, specifically
FeO.1/2Fe2O3
1/2Cu2O.CuO
VO.1/2V2O3
V2O3.V2O5
VO2.1/2V2O5
VO2.1/2V2O3
MnO.1/2Mn2O3
1/2Mn2O3.1/2Mn2O3
SnO.SnO2
TiO.1/2Ti2O3
1/2Ti2O3.TiO2
MoO2.MoO3 or
WO2.WO3
The mixed oxides according to the invention are prepared using known methods, preferably by intimate mixing of the individual oxides by known ceramic technologies, pressing the mixtures under pressure to form moldings of, for example, cuboid configuration, or mixing in slurries of the individual oxides and pouring the slurries into appropriate molds, subsequently removing the suspension medium and sintering the moldings in an inert atmosphere, e.g. under argon, at temperatures from 900 to 1700xc2x0 C.
The materials according to the invention are hence prepared by known methods, the element compounds e.g. by sintering the element powders at high temperatures, but below the melting point, or by melting in a high vacuum and subsequent powdering and sintering. The oxides are synthesized e.g. by sintering the powder mixtures of the individual oxides. The expression xe2x80x9ccombinatorialxe2x80x9d, as used here, refers specifically to this preparation, in particular the sintering.
The thermoelectrically active mixed oxides can also be prepared by reactive sintering of the corresponding metal mixtures in air at elevated temperatures. For economic reasons, it is also expedient to use mixtures of oxides and metals.
It is also an object of the invention to optimize the materials in terms of efficiency. It is obvious that, when the components are varied by, for example, 5 atom %, very many materials need to be synthesized and tested. We have found that this object is achieved by combinatorial methods. To that end, element alloys or oxide mixtures or mixtures of elements with oxides, with gradual variation of the composition as a function of the length coordination on a substrate, can be produced by producing the elements or already binary alloys, from appropriate targets, on a substrate provided with a perforated mask, the element composition changing as a function of the distance from the target or as a function of the sputtering angle. The mask is subsequently removed, and the xe2x80x9cdotsxe2x80x9d which are produced are sintered to form the actual materials. The expression xe2x80x9cdotxe2x80x9d refers in this case to points or regions of the material which are spatially separated from one another on a substrate, which have essentially the same extents and which are preferably arranged at regular intervals, so that an array is obtained. xe2x80x9cArrayxe2x80x9d means a two-dimensional, essentially uniformly spaced arrangement of dots on a substrate surface. It is also possible to suspend element and oxide powders having particle sizes smaller than 5 xcexcm in an inert suspension medium, such as hydrocarbons, with the participation of a dispersing agent to form sufficiently stable suspensions, and to deposit mixtures of the suspensions as droplets, in the manner described for the oxides, to evaporate the suspension medium and to sinter on the substrate the powder mixtures formed in this way.
Besides metallic substrates, silicon carbide, which is also sufficiently electrically conductive, is preferred as an inert substrate material which is stable with respect to temperature and diffusion.
Dots of the oxides can be produced on a substrate surface by using doping machines to deposit mixtures of salts, preferably nitrates or other soluble compounds, in the form of drops with variable composition, evaporating the solvent, preferably water, converting the nitrates or compounds into the oxides by raising the temperature and subsequently sintering the oxide mixtures in their entirety.
Per substrate plate with dimensions of the order of 10*10 cm, from 1000 to 10,000 dots with size (diameters) of from 0.2 to 2 mm are applied.
It may also be favorable to introduce the element or oxide mixtures as a suspension into a plate having angular cavities, to extract the suspension medium under reduced pressure, to melt or sinter the material and then to test the small cubes or blocks hence obtained. The cavities may also be cuboid with dimensions in the millimeter range. For example, cuboid cavities with the dimensions 6xc3x975xc3x979 mm may be used.
One advantage of this procedure is that the size proportions are preserved in the finished generator or Peltier module. Such a plate may, for example, contain from 20 to 100 cavities.
Fast and reliable testing of the materials is essential. According to the invention, two analysis methods may be implemented for this purpose:
The invention relates to a process for the combinatorial preparation and testing of semiconductor materials for thermoelectric generators, in which an array of dots of the semiconductor materials with different composition is produced on a conductive two-dimensional substrate, the substrate is heat-treated, preferably under an inert gas such as nitrogen or argon, with the array to a desired measurement temperature and the dots are respectively brought into contact with a cooled measurement pin, the voltage without load, the current and the voltage with a decreasing load resistance and/or the short-circuit current being measured, subsequently stored and evaluated. Since the material and specimens are automatically at the temperature of the substrate plate, it is only when the cooled measurement pin is applied that a temperature gradient which grows within seconds is produced, which generates a short-circuit current varying as a function of temperature, which is measured and whose profile is stored. The invention also relates to a process for the combinatorial preparation and testing of semiconductor materials for thermoelectric generators, in which an array of dots of the semiconductor materials with different composition is produced on a conductive two-dimensional substrate, the dots are brought into contact on the opposite side from the substrate with a conductive non-magnetic plate, the substrate and the plate are kept at different temperatures and are electrically connected to one another, the plate being scanned with a magnetic-field probe and the measured data being stored and evaluated.
For both methods, the dots situated on the metallic or silicon-carbide substrate are ground to a uniform height e.g. by using a microfine grinding disk, a plane surface with a small roughness depth being obtained at the same time. The substrate plate is brought to a measurement temperature, and the dots are brought into contact with a cooled measurement pin under a defined application force.
Conversely, it is also possible to leave the substrate plate cold and to heat the measurement pin. In this case, the heating should not be carried out electrically, but rather, in order to prevent the incorporation of spurious currents, purely thermally, for example by focusing an infrared laser suitably onto the measurement pin.
While the measurement pin is being applied, the voltage without load, the current and the voltage with a decreasing load resistance as well as the short-circuit current are measured. Computer-controlled measurement equipment requires about 10 seconds in order to measure one material, including travel to the next dot, which makes it possible to measure approximately 10,000 dots per day at one temperature. If operation is carried out with a plurality of measurement pins in parallel, then a correspondingly larger number of dots can be measured. The measured values and curves can be stored and graphically processed, so that a graphical representation indicates, at a glance, the better materials whose composition is then analyzed using standard methods. Operation is preferably carried out under an inert gas.
A further, but contactless testing/evaluation method consists in applying a further conductive non-magnetic cooled plate to the dots, which are situated on the conductive/metallic substrate plate, and in electrically connecting the two plates to one another. At the applied temperature difference, each dot is short-circuited. The short-circuit current generates local magnetic fields in the dots and in the surrounding parts of the plate. The plate is scanned with a magnetic-field probexe2x80x94e.g. a Hall probe or a squidxe2x80x94and the measurement values are stored in a computer as a function of the coordinates. The strength of the magnetic field is proportional to the short-circuit current, and its direction indicates whether the material is p- or n-conducting. Appropriate graphical processing of the measured values shows the particularly advantageous dots at a glance.
With this method, 10,000 dots can be measured within 5 to 30 min., but only with respect to doping and the short-circuit current.

Thermoelectrically active materials and generators and Peltier arrangements containing them

Abstract: with

Abstract: SA, SB=B, C, Si, Ge, Sb, Se or Te,

Abstract: with

Abstract: Me=Fe, Cu, V, Mn, Sn, Ti, Mo, W

Abstract: n=integer from 1 to 6,

Abstract: a=1 or 2,

Abstract: f=number from 0.2 to 5,

Abstract: k=number from 0,01 to 2,


These compounds contain an oxetane functionality and a cinnamyl functionality. The oxetane functionality is homopolymerizable in reactions that can undergo cationic or anionic ring opening, and the cinnamyl functionality is polymerizable with compounds such as electron acceptor compounds. The dual functionality allows for dual cure processing. The generic structure of such compounds is

This invention relates to oxetane compounds containing cinnamyl functionality.
Oxetanes are highly reactive cyclic ethers that can undergo both cationic and anionic ring opening homopolymerization. Cinnamyl compounds are capable of free radical polymerization.
This invention relates to compounds that contain an oxetane functionality and a cinnamyl functionality. These compounds can be homopolymerizable in reactions in which the oxetane can undergo cationic or anionic ring opening, or polymerizable with compounds such as electron acceptor compounds. The dual functionality allows for dual cure processing, both thermal cure or radiation cure. This capability makes them attractive for use in many applications, such as, adhesives, coatings, encapsulants, and composites.
In one embodiment, the compounds of this invention can be represented by the formula
in which R is a methyl or ethyl group, X and Y independently are a direct bond, provided both are not direct bonds, or an ether, ester, or carbamate group, and Q is a divalent hydrocarbon. The actual configuration of the Q portion will depend on the configuration of the starting compounds.
The starting cinnamyl compound can be small molecule, for example, cinnamyl alcohol or cinnamyl chloride, or can be an oligomeric or polymeric molecule, prepared by reacting cinnamyl alcohol or cinnamyl chloride with one functionality on a difunctional oligomer or polymer.
Whether the starting cinnamyl compound is a small molecule or an oligomeric or polymeric material, it will contain a cinnamyl functionality represented by the structural formula
and a second functionality reactive with a second functionality on the starting oxetane compound. For example, the cinnamyl starting materials disclosed above contain halogen or hydroxyl functionality in addition to the cinnamyl functionality.
The starting oxetane compound can be a small molecule or an oligomeric or polymeric molecule, prepared, for example, by reacting one of the small molecule oxetane starting compounds disclosed below with one functionality on a difunctional oligomer or polymer. In either case, it will contain an oxetane functionality represented by the structure
and a second functionality reactive with the second functionality on the cinnamyl starting compound.
Suitable starting oxetane compounds that are small molecules include, for example,
(a) alcohols, such as, 3-methyl-3-hydroxymethyloxetane, 3-ethyl-3-hydroxymethyloxetane;
(b) halides, such as, 3-methyl-3-bromomethyloxetane, 3-ethyl-3-bromomethyloxetane, which can be prepared by the reaction of an alcohol from (a) with CBr4 as is known in the art;
(c) alkyl halides, such as, 3-methyl-3-alkylbromomethyloxetane, 3-ethyl-3-alkylbromomethyloxetane, which can be prepared from the reaction of an alkyl dibromide compound with an oxetane alcohol from (a) as is known in the art;
and (d) tosylates, such as, 3-methyl-3-tosylmethyloxetane, 3-ethyl-3-tosylmethyl-oxetane, which can be prepared from p-toluenesulfonyl chloride:
When a longer chain and higher molecular weight compound containing cinnamyl and oxetane is desired, either the starting cinnamyl compound or the starting oxetane compound, or both, may be reacted with a difunctional oligomeric or polymeric material. The second functionality on this oligomeric or polymeric material must be reactive with the oxetane starting compound if the first reaction was between the cinnamyl starting compound and the difunctional oligomeric or polymeric material, and with the cinnamyl starting compound if the first reaction was between the oxetane starting compound and the difunctional oligomeric or polymeric material. Examples of suitable and commercially available oligomers and polymers include dimer diol and poly(butadiene) with terminal hydroxyl functionality.
In the case in which both the oxetane and cinnamyl starting compounds are oligomeric or polymeric, Q may also contain a functionality, for example, an ether, ester, carbamate, or urea functionality, resulting from the reaction of the two oligomeric or polymeric starting materials.
In general, the inventive compounds containing oxetane and cinnamyl functionality are prepared by reacting together a starting compound containing oxetane functionality and a second functionality and a starting compound containing cinnamyl functionality and a second functionality reactive with the second functionality on the oxetane compound. Typical reaction schemes include well known addition, substitution, and condensation reactions.
In a further embodiment, the compounds of this invention include polymeric compounds that contain more than one oxetane and more than one cinnamyl functionality. Such compounds are prepared from a polymeric starting compound from which depend functionalities that are reactive with the starting oxetane compound and the starting cinnamyl compound.
The polymeric compound will have the structure
in which polymer represents a polymeric backbone from which depend the oxetane and cinnamyl functionalities, m and n are integers that will vary with the level of oxetane and cinnamyl functionality added by the practitioner and typically each will be from 2 to 500, R is methyl or ethyl, and W and Z are independently an ether, ester, or carbamate group (formed through the reaction of a pendant functionality on the polymer and a corresponding reactive functionality on the starting oxetane compound or starting cinnamyl compound).
The pendant functionalities on the polymer may be connected to the polymeric backbone by a hydrocarbon, for example, one having one to twenty carbons, that itself is dependent from the polymeric backbone. For purposes of this specification, those dependent moieties will be deemed to be part of the polymeric backbone.
An example of a commercially available and suitable polymeric backbone is poly(butadiene) having pendant hydroxyl groups. The pendant hydroxyl groups can be reacted with the oxetane starting compound containing the tosyl leaving group and with cinnamyl chloride. In this case, the linking groups W and Z will be an ether functionality.
As a further example, a poly(butadiene) having pendant carboxylic acid functionality can react with the hydroxyl functionality on either of the hydroxyl oxetane starting materials and with the hydroxyl functionality on cinnamyl alcohol. In this case, the W and Z groups will be an ester functionality.
Polymeric starting material can be purchased commercially, for example, there are available acrylonitrile-butadiene rubbers from Zeon Chemicals and styrene-acrylic copolymers from Johnson Polymer. The pendant functionalities from these polymers are hydroxyl or carboxylic acid functionality.
Other starting polymeric materials can be synthesized from acrylic and/or vinyl monomers using standard polymerization techniques known to those skilled in the art. Suitable acrylic monomers include xcex1,xcex2-unsaturated mono and dicarboxylic acids having three to five carbon atoms and acrylate ester monomers (alkyl esters of acrylic and methacrylic acid in which the alkyl groups contain one to fourteen carbon atoms).
Examples are methyl acryate, methyl methacrylate, n-octyl acrylate, n-nonyl methacrylate, and their corresponding branched isomers, such as, 2-ethylhexyl acrylate. Suitable vinyl monomers include vinyl esters, vinyl ethers, vinyl halides, vinylidene halides, and nitriles of ethylenically unsaturated hydrocarbons. Examples are vinyl acetate, acrylamide, 1-octyl acrylamide, acrylic acid, vinyl ethyl ether, vinyl chloride, vinylidene chloride, acrylonitrile, maleic anhydride, and styrene.
Other polymeric starting materials can be prepared from conjugated diene and/or vinyl monomers using standard polymerization techniques known to those skilled in the art. Suitable conjugated diene monomers include butadiene-1,3,2-chlorobutadiene-1,3, isoprene, piperylene and conjugated hexadienes. Suitable vinyl monomers include styrene, xcex1-methylstyrene, divinylbenzene, vinyl chloride, vinyl acetate, vinylidene chloride, methyl methacrylate, ethyl acrylate, vinylpyridine, acrylonitrile, methacrylonitrile, methacrylic acid, itaconic acid and acrylic acid.
Those skilled in the art have sufficient expertise to choose the appropriate combination of those monomers and subsequent reactions to be able to add pendant functionality, for example, hydroxyl and carboxyl functionality, for adding the oxetane and cinnamyl functionalities as disclosed in this specification.

Oxetane compounds containing cinnamyl functionality

Abstract: in which R is a methyl or ethyl group, X and Y independently are a direct bond, or an ether, ester, or carbamate group, and Q is a divalent hydrocarbon (which may contain heteroatoms of N, O, or S), provided that X and Y will not both be direct bonds in the same molecule.

National Starch and Chemical Investment Holding Corporation


A medical device can be used to entrain biological or foreign material during a medical procedure for the fragmentation of the material. The device also can be used to remove the material safely from the body. The device has a core element with a first portion extending substantially longitudinally and a second portion wound to form at least a helical coil in the shape of cone. A flat wire can substantially wrap the first and second portions of the core element, or a wire can substantially wrap the first portion and a sheath can substantially cover the second portion.

This invention relates to medical treatments of objects within anatomical lumens of the body, and more specifically, to devices and methods for entraining and extracting such objects from within the body.
Concretions can develop in certain parts of the body, such as in the kidneys, pancreas, and gallbladder. Minimally invasive medical procedures generally involve causing limited trauma to the tissues of a patient, and can be used to dispose of problematic concretions. Lithotripsy and ureteroscopy, for example, are used to treat urinary calculi (e.g., kidney stones) in the ureter of patients.
Lithotripsy is a medical procedure that uses energy in various forms such as acoustic shock waves, pneumatic pulsation, electrical hydraulic shock waves, or laser beams to break up biological concretions such as urinary calculi (e.g., kidney stones). The force of the energy, when applied either extracorporeally or intracorporeally, usually in focused and continuous or successive bursts, comminutes a kidney stone into smaller fragments that may be extracted from the body or allowed to pass through urination. With the help of imaging tools such as transureteroscopic video technology and fluoroscopic imaging, the operator of the lithotripter device can monitor the progress of the medical procedure and terminate treatment when residual fragments are small enough to be voided or removed.
Intracorporeal fragmentation of urinary calculi can prove problematic in that stones and/or stone fragments in the ureter may become repositioned closer to and possibly migrate back toward the kidney, thereby requiring further medical intervention to prevent the aggravation of the patient""s condition. It is desirable to be able to extract such fragments from the body using a single instrument, to prevent the need for successive instrumentation.
Many known stone extraction devices are rigid and lack the maneuverability and flexibility to engage and disengage repeatedly a stone without harming the surrounding tissue. For example, if a stone is still too large to be extracted without further fragmentation, it can be difficult to disengage the stone from such an extraction device without damaging the delicate lining of the ureteral wall.
The present invention mitigates the risk of damage to surrounding body tissue when treating and/or removing organic material (e.g., blood clots, tissue, and biological concretions such as urinary, biliary, and pancreatic stones) and inorganic material (e.g., components of a medical device or other foreign matter), which may obstruct or otherwise be present within the body""s anatomical lumens. In one embodiment, the invention prevents the upward migration of stone fragments generated during a stone fragmentation procedure and safely and efficiently extracts fragments from the body. The invention also enables repeated application to stones, stone fragments, and other biological and nonbiological/foreign material while minimizing trauma to the surrounding tissue.
A medical device, in accordance with an embodiment of the invention, comprises a core element made at least partially of a shape-memory material. Shape-memory material is a material that can be formed into a particular shape, retain that shape during resting conditions (e.g., when the shaped material is in free space or when external forces applied to the shaped material are insufficient to substantially deform the shape), be deformed into a second shape upon subjecting the initial shape to a sufficiently strong external force, and revert substantially back to the initial shape once the external force is no longer applied. Examples of shape memory material includesynthetic plastics, stainless steel, and superelastic, metallic alloys of nickel/titanium (commonly referred to as nitinol), copper, cobalt, vanadium, chromium, iron, or the like. In one embodiment, a first portion of the core element extends substantially longitudinally, and a second portion is wound to form a helical coil. The helical coil is adapted to taper from a larger diameter at a proximal end thereof to a smaller diameter at a distal end thereof, thereby resembling a helical cone shape.
In one embodiment, a flat wire (with, for example, a square, rectangular, or other quadrilateral cross-section) substantially wraps the first and second portions of the core element. A distal end of the flat wire can be attached to the distal end of the helical coil, so as to maintain the relative orientation and position between the flat wire and the core element. In a further embodiment, a layer of polymeric material substantially covers the entire outer surface of the flat wire (i.e., the surface of the flat wire that contacts the walls of the anatomical lumen or catheter), including that portion of the flat wire that wraps both the first and second portions of the core element. In another embodiment, the polymeric layer covers a portion of the outer surface of the flat wire wrapping the second portion of the core element, while leaving the outer surface of the flat wire wrapping the first longitudinal portion of the core element uncovered. Alternatively, the polymeric layer covers the outer surface of the flat wire wrapped about the second portion of the core element and at least a portion of the first longitudinal section in the vicinity of the helical cone.
In another embodiment, a wire element substantially wraps only the first longitudinal portion of the core element, and a sheath (of, for example, a polymeric material) covers the second, helical cone portion of the core element. The proximal end of the sheath can be attached to the distal end of the wire element, and the distal end of the sheath can be attached to the distal end of the second portion of the core element.
In yet another embodiment, the curved, second portion of the core element is covered substantially by a polymeric material and the longitudinal section of the core element remains uncovered. In this embodiment, the core element is not covered by a wire element.
In one embodiment, the polymeric material/layer is applied by spraying. For example, a polymeric material can be spray-coated onto the outer surface of the wire and/or directly onto the helical cone section of the core element. In another embodiment, the polymeric material can be a sheath that is heat-shrunk about the wire and/or the second portion of the core element. The polymeric sheath can be made of PTFE, EPTFE, ETFE or other suitable material that exhibits a light color capable of reflecting most of the laser energy used during a lithotripsy procedure and absorbing or dissipating the energy not reflected with no or minimal damage to the polymeric sheath at normal laser operating levels.
The polymeric sheath preferably comprises a plurality of colors along a length of the sheath in order to assist the physician who is performing the lithotripsy procedure to detect movement in the sheath and to assist in gauging distances. In this manner, the physician can determine not only when the second portion of the core element (corresponding to the curved or helical cone section of the core element) is deployed/expanded, but also the configuration of the core element during various phases of the lithotripsy procedure. In one embodiment, the polymeric sheath exhibits the standard color of a PTFE heat shrink extrusion with a colored stripe along the length of the sheath. As the medical device is manipulated, the relative size and distances of the wound sections of the helical coil can be readily determined by examining the spiral configuration of the colored stripe, which appears about the wound section of the core element. The striped color is also preferably selected to be resistant to and reflect laser energy so as to minimize damage to the polymeric sheath.
The helical cone is adapted to ensnare objects of various sizes from within an anatomical lumen, e.g., a kidney stone from within a ureter. Superelastic properties of the helical cone can enable it to unwind and assume a substantially linear configuration upon being subjected to a pulling force along a longitudinal axis of the core element, such as when the helical cone is pulled within a catheter adapted to receive the core element, the wire, and the polymeric sheath. The cone can be pulled into an outer catheter when a captured stone or other object is too large to pass through the anatomical lumen without further fragmentation or other treatment. The helical cone substantially rewinds into its helical cone rest state when released and unrestrained by such a force.
The substantially linear configuration of the helical cone when positioned within the catheter enables the catheter to retain a small diameter, which facilitates the placement of the catheter beyond the object in the anatomical lumen. Once the catheter is properly positioned, the second portion of the core element is pushed out of the distal end of the catheter where the helical cone substantially rewinds or expands back into its tapered configuration. As discussed, the helical cone can be reversibly transformed into a substantially linear configuration when drawn into the catheter so that it can be repeatably positioned and deployed in more advantageous locations.
In yet another aspect, the second portion of the core element forms one or more curved shapes in addition to the helical cone, such as another helical cone or a single loop. The single loop or curved element can be located near the proximal end of the helical cone in order to assist in the manipulation, extraction, or repositioning of the kidney stone or other object in the anatomical lumen. The second helical cone can be located near the distal end of the first helical cone so that if the first helical cone unwinds and is pulled into the catheter when a kidney stone or other object is too large to pass through the anatomical lumen, the second helical cone can serve as a backstop during the subsequent treatment procedure without having to redeploy the first helical cone.
Regardless of the particular curved element employed, the curved element can be made of or include superelastic/shape-memory material that enables the deformation and reformation of the curved element as described above in connection with the helical cone. Similarly, the curved element can be wrapped entirely by a wire element, such as round or flat wire, or can be covered by a polymeric material as described above in connection with the helical cone. Those skilled in the art will recognize that the various wire wrapping and polymeric covering embodiments previously discussed in connection with the helical cone can be used as well for the curved element. The wire wrapping and polymeric covering techniques can also be common or different as between the curved element and the helical cone. For example, the first longitudinal portion of the core element can be wrapped in flat wire, while the curved element and helical cone are covered by a polymeric sheath. Alternatively, the first longitudinal portion of the core element can be uncovered, while the shaped portion(s) of the core element are covered with a polymeric sheath, which can comprise a plurality of laser resistant colors.
The foregoing and other objects, aspects, features, and advantages of the invention will become more apparent from the following description and from the claims.

Treatment and removal of objects in anatomical lumens


Drug delivery devices, and methods of delivering pharmaceutically active agents to a target tissue within a body using such devices, are disclosed. One drug delivery device includes a body having an internal surface for placement proximate a target tissue and a well having an opening to the internal surface. An inner core comprising a pharmaceutically active agent is disposed in the well.

The present invention generally pertains to biocompatible implants for localized delivery of pharmaceutically active agents to body tissue. More particularly, but not by way of limitation, the present invention pertains to biocompatible implants for localized delivery of pharmaceutically active agents to the posterior segment of the eye.
Several diseases and conditions of the posterior segment of the eye threaten vision. Age related macular degeneration (ARMD), choroidal neovascularization (CNV), retinopathies (i.e. diabetic retinopathy, vitreoretinopathy), retinitis (i.e. cytomegalovirus (CMV) retinitis), uveitis, macular edema, and glaucoma are several examples.
Age related macular degeneration (ARMD) is the leading cause of blindness in the elderly. ARMD attacks the center of vision and blurs it, making reading, driving, and other detailed tasks difficult or impossible. About 200,000 new cases of ARMD occur each year in the United States alone. Current estimates reveal that approximately forty percent of the population over age 75, and approximately twenty percent of the population over age 60, suffer from some degree of macular degeneration. xe2x80x9cWetxe2x80x9d ARMD is the type of ARMD that most often causes blindness. In wet ARMD, newly formed choroidal blood vessels (choroidal neovascularization (CNV)) leak fluid and cause progressive damage to the retina.
In the particular case of CNV in ARMD, two main methods of treatment are currently being developed, (a) photocoagulation and (b) the use of angiogenesis inhibitors. However, photocoagulation can be harmful to the retina and is impractical when the CNV is near the fovea. Furthermore, photocoagulation often results in recurrent CNV over time. Oral or parenteral (non-ocular) administration of anti-angiogenic compounds is also being tested as a systemic treatment for ARMD. However, due to drug-specific metabolic restrictions, systemic administration usually provides sub-therapeutic drug levels to the eye. Therefore, to achieve effective intraocular drug concentrations, either an unacceptably high dose or repetitive conventional doses are required. Periocular injections of these compounds often result in the drug being quickly washed out and depleted from the eye, via periocular vasculature and soft tissue, into the general circulation. Repetitive intraocular injections may result in severe, often blinding, complications such as retinal detachment and endophthalmitis.
In order to prevent complications related to the above-described treatments and to provide better ocular treatment, researchers have suggested various implants aimed at localized delivery of anti-angiogenic compounds to the eye. U.S. Pat. No. 5,824,072 to Wong discloses a non-biodegradable polymeric implant with a pharmaceutically active agent disposed therein. The pharmaceutically active agent diffuses through the polymer body of the implant into the target tissue. The pharmaceutically active agent may include drugs for the treatment of macular degeneration and diabetic retinopathy. The implant is placed substantially within the tear fluid upon the outer surface of the eye over an avascular region, and may be anchored in the conjunctiva or sclera; episclerally or intrasclerally over an avascular region; substantially within the suprachoroidial space over an avascular region such as the pars plana or a surgically induced avascular region; or in direct communication with the vitreous.
U.S. Pat. No. 5,476,511 to Gwon et al. discloses a polymer implant for placement under the conjunctiva of the eye. The implant may be used to deliver neovascular inhibitors for the treatment of ARMD and drugs for the treatment of retinopathies, retinitis, and CMV retinitis. The pharmaceutically active agent diffuses through the polymer body of the implant.
U.S. Pat. No. 5,773,019 to Ashton et al. discloses a non-bioerodable polymer implant for delivery of certain drugs including angiostatic steroids and drugs such as cyclosporine for the treatment of uveitis. Once again, the pharmaceutically active agent diffuses through the polymer body of the implant.
All of the above-described implants require careful design and manufacture to permit controlled diffusion of the pharmaceutically active agent through a polymer body (matrix devices) or polymer membrane (reservoir devices) to the desired site of therapy. Drug release from these devices depends on the porosity and diffusion characteristics of the matrix or membrane, respectively. These parameters must be tailored for each drug moiety to be used with these devices. Consequently, these requirements generally increase the complexity and cost of such implants.
U.S. Pat. No. 5,824,073 to Peyman discloses an indentor for positioning in the eye. The indentor has a raised portion that is used to indent or apply pressure to the sclera over the macular area of the eye. This patent discloses that such pressure decreases choroidal congestion and blood flow through the subretinal neovascular membrane, which, in turn, decreases bleeding and subretinal fluid accumulation.
Therefore, a need exists in the biocompatible implant field for a surgically implantable drug delivery device capable of safe, effective, rate-controlled, localized delivery of a wide variety of pharmaceutically active agents to any body tissue. The surgical procedure for implanting such a device should be safe, simple, quick, and capable of being performed in an outpatient setting. Ideally, such a device should be easy and economical to manufacture. Furthermore, because of its versatility and capability to deliver a wide variety of pharmaceutically active agents, such an implant should be capable of use in clinical studies to deliver various agents that create a specific physical condition in a patient or animal subject. In the particular field of ophthalmic drug delivery, such an implantable drug delivery device is especially needed for localized delivery of pharmaceutically active agents to the posterior segment of the eye to combat ARMD, CNV, retinopathies, retinitis, uveitis, macular edema, and glaucoma.
One aspect of the present invention comprises a drug delivery device including a body having an internal surface for placement proximate a target tissue and a well having an opening to the internal surface. An inner core comprising a pharmaceutically active agent is disposed in the well.
In another aspect, the present invention comprises a method of delivering a pharmaceutically active agent to a target tissue within a body. A drug delivery device is provided. The drug delivery device includes a body having an internal surface and a well having an opening to the internal surface, and an inner core disposed in the well comprising a pharmaceutically active agent. The device is disposed within the body so that the pharmaceutically active agent is in communication with the target tissue through the opening.
In a further aspect, the present invention comprises an ophthalmic drug delivery device including a body having a scleral surface for placement proximate a sclera and a well or cavity having an opening to the scleral surface. An inner core comprising a pharmaceutically active agent is disposed in the well.
In a further aspect, the present invention comprises a method of delivering a pharmaceutically active agent to an eye having a sclera. A drug delivery device is provided. The drug delivery device includes a body having a scleral surface and a well having an opening to the scleral surface, and an inner core disposed in the well comprising a pharmaceutically active agent. The device is disposed within the eye so that the pharmaceutically active agent is in communication with the sclera through the opening.
In a further aspect, the present invention comprises a method of delivering a pharmaceutically active agent to an eye having a sclera, a Tenon""s capsule, and a macula. A drug delivery device comprising a body having a pharmaceutically active agent disposed therein is provided. The device is disposed on an outer surface of the sclera, below the Tenon""s capsule, and proximate the macula.


Methods for treating and reducing risk of cerebral amyloid angiopathy (CAA) using nasal vaccination with a proteosome adjuvant.

Cerebrovascular dysfunction is a fundamental part of the pathology of several neurodegenerative diseases and rated as one of the most prominent cause for dementia. Cerebral amyloid angiopathy (CAA) results in intra-parenchymal and subarachnoid bleeding, which is caused by cerebrovascular amyloid deposits and multiple infarcts, and can lead to hemorrhagic stroke and cognitive impairment (Greenberg et al. Stroke. 2004; 35:2616-2619; Frangione et al. Amyloid. 2001; 8 Suppl 1:36-42). The prevalence of CAA, estimated from autopsy series, is approximately 10% to 40% of the general elderly population (Greenberg et al. Stroke. 2004; 35:2616-2619). Although the most common form of cerebrovascular amyloid is Aβ-CAA, there are other proteins that have been linked to familial forms of CAA such as: APP, cystatin C, BRI, prion protein, gelsolin, and transthyretin (Burgermeister et al. Lessons from mouse models. Ann NY Acad Sci. 2000; 903:307-316). Clinical interventions usually consist of blood pressure control (i.e., hypertension treatment) as well as avoidance of medications that increase systemic hemorrhage risk (e.g., aspirin). However, there are no current treatments to reduce amyloid pathology in CAA (Maia et al. J Neurol Sci. 2007; 257:23-30).

Methods of treating cerebral amyloid angiopathy