Abstract: A therapeutic composition is provided including a polysaccharide or a cationic peptide dissolved in an organic substance. The polysaccharide can be heparin or a derivative of heparin. The cationic peptide can be L-arginine, oligo-L-arginine or poly-L-arginine. The organic substance can be formamide. A method of coating an implantable medical device is also provided, comprising applying the therapeutic composition to the device and allowing the organic substance to evaporate. The device can be a stent.

Abstract: The present invention is directed to an intermediate composition for producing a muscle tissue matrix suitable for implantation in humans, comprising shredded, allogeneic human muscle tissue that has been combined with an aqueous carrier, preferably a biocompatible acid solution, to form a muscle tissue slurry having a viscosity within the range of 1 centistoke to 20,000 centistokes measured at 25° C. In another aspect, the present invention is directed to a tissue implant comprising a human muscle tissue matrix.

Abstract: The invention provides a biocompatible composite for use in a living subject for purposes of repairing damaged tissues and reconstructing a new tissue. The composite includes a biodegradable or absorbable three-dimensional support construct, a liquid or viscous fluid forming a gel matrix or viscous fluid when delivered to an area of interest in a living subject. The biodegradable construct provides an ideal surface for cell or cell extract attachment, while the gel matrix or viscous fluid acts as both a carrier material and a separator for maintaining the space between the constructs as well as the structural integrity of the developing issue.

Abstract: An osmotic delivery system has a membrane plug retention mechanism which can also be used to control the delivery rate of a beneficial agent from the osmotic delivery system. The osmotic delivery device includes an implant capsule containing a beneficial agent and an osmotic agent. Holes are formed along a side wall of the implant capsule at an open end of the capsule. When the membrane plug is inserted into the open end of the capsule, the membrane material swells into the holes in the capsule side wall creating a large frictional force which prevents expulsion of the membrane plug. A beneficial agent delivery rate of the osmotic delivery system is controllable by varying the size and number of the holes to change the amount of exposed surface area of the membrane plug. An increase in the surface area of the membrane plug exposed to the exterior environment causes a corresponding increase in the liquid permeation rate of the membrane and thus, increases the beneficial agent delivery rate.

Abstract: An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual. The vehicle is particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and can also be used advantageously for delivery of high molecular weight products, such as products larger than IgG. A method of making a biocompatible, immunoisolatory implantable vehicle, consisting in a first embodiment of a coextrusion process, and in a second embodiment of a stepwise process.

Abstract: The present invention is directed to an implantable immune modulation device that is useful for modulating an immune response in mammals, comprising a plurality of fibers, within a porous shell. The fiber filling is loaded with single or multiple antigens, and optionally one or more biologically active compounds such as cytokines (e.g. lymphokines, chemokines etc.), attachment factors, genes, peptides, proteins, nucleotides, carbohydrates or cells depending on the application.

Abstract: Crosslinked compositions formed from water-insoluble copolymers are disclosed. These compositions are copolymers having a bioresorbable region, a hydrophilic region and at least two cross-linkable functional groups per polymer chain. Crosslinking of these polymers can be effected in solution in organic solvents or in solvent-free systems. If crosslinking occurs in a humid environment, a hydrogel will form. If crosslinking occurs in a non-humid environment, a xerogel will form which will form a hydrogel when exposed to a humid environment and the resulting crosslinked materials form hydrogels when exposed to humid environments. These hydrogels are useful as components in medical devices such as implantable prostheses. In addition, such hydrogels are useful as delivery vehicles for therapeutic agents and as scaffolding for tissue engineering applications.

Abstract: A method for producing antibiotic composites is described, which is characterized in that a salt, which can be subjected to plastic deformation and which consists of at least one cationic component of a protonated antibiotics base from the groups of aminoglycoside antibiotics, the lincosamide antibiotics and the tetracycline antibiotics and of at least one anionic components from the group of organic sulfates and/or organic sulfonates and/or fatty acid esters, is used as a binding agent for the fixation of inorganic composite components and/or possibly organic composite components and possibly for the molding of the composites while adding water, especially through pressing, extrusion, rolling, calendering and grinding processes.

Abstract: The present invention provides a novel substrate for use in growing cells and for the study of mechanobiology. The membrane of the present invention comprises appropriate microtopography and surface chemical modifications to facilitate the production of adherent and oriented cells that phenotypically resemble cells in vivo.

Abstract: The invention features articles for delivery of a biologically active substance, methods for making such articles, and methods for treating an animal using the articles.

Abstract: An osmotic pump having a minimally compliant, volume-efficient piston positioned within a capsule is provided. The capsule has an interior surface, a beneficial agent, and an osmotic agent. The piston is movable with respect to an interior surface of the capsule, and defines a movable seal with the interior surface of the capsule. The movable seal separates the osmotic agent from the beneficial agent. The piston has a length-to-total-diameter ratio of about 1.1:1 and a core-diameter-to-total-diameter ratio of about 0.9:1. The piston enables greater beneficial agent and/or osmotic agent payload without increasing the size of the capsule. The osmotic agent imbibes liquid from a surrounding environment through a semipermeable body to cause the piston to move and, in turn, cause delivery of the beneficial agent from the capsule.

Abstract: A process for producing microparticles, in which an aqueous solution of purified amylopectin-based starch of reduced molecular weight is prepared, the solution is combined with biologically active substance, an emulsion of starch droplets is formed in an outer phase of polymer solution, the starch droplets are made to gel, the gelled starch particles are dried, and a release-controlling shell is optionally applied to the particles, wherein at least one buffer substance having the ability of keeping the pH of the produced microparticles above 3 if exposing the microparticles to an aqueous evironment is added at any stage during the process. Microparticles which essentially consist of said starch, have an amino acid content of less than 50 ?g and have no covalent chemical cross-linking and which have the aktivity of keeping the pH above 3 if exposed to a aqueous environment.

Abstract: Encapsulated producer cells which are capable of expressing a molecule which is an inhibitor of CNS tumour growth provide a novel approach to the treatment of tumours, such as brain tumors which are localized within the central nervous system.

Abstract: The present invention relates to new silver-ion super-complex compositions. More particularly, the present invention describes silver-ion super-complex compositions comprising a silver-thiosulfate ion complex further complex with a primary, secondary or tertiary amine. These silver-ion super-complex compositions are stable in a saline environment and have improved solvent miscibility.

Abstract: Coatings for implantable devices or endoluminal prosthesis, such as stents, are provided, including a method of forming the coatings. The coatings can be used for the delivery of an active ingredient or a combination of active ingredients.

Abstract: An osmotic delivery system has a membrane plug retention mechanism which can also be used to control the delivery rate of a beneficial agent from the osmotic delivery system. The osmotic delivery device includes an implant capsule containing a beneficial agent and an osmotic agent. Holes are formed along a side wall of the implant capsule at an open end of the capsule. When the membrane plug is inserted into the open end of the capsule, the membrane material swells into the holes in the capsule side wall creating a large frictional force which prevents expulsion of the membrane plug. A beneficial agent delivery rate of the osmotic delivery system is controllable by varying the size and number of the holes to change the amount of exposed surface area of the membrane plug. An increase in the surface area of the membrane plug exposed to the exterior environment causes a corresponding increase in the liquid permeation rate of the membrane and thus, increases the beneficial agent delivery rate.

Abstract: Described are heat stable aqueous solutions or gels comprising a biologically effective amount of a protein and an effective stabilizing amount of a polysaccharide gum as well as heat stable solutions or gels suitable for use in an implantable drug delivery device at body temperature. Also disclosed are lyophilized compositions having biologically activity, where such lyophilized compositions are formed by lyophilizing the stabilized solutions or gels of the invention.

Abstract: A melanoma inhibiting activity factor (MIA), preferably in combination with an osteoinductive protein, is a useful pharmaceutical agent for promoting bone healing and/or cartilage repair.

Abstract: The invention provides a composition for promoting regeneration of tissue which has degenerated in a subject as a result of a disease or disorder and a method of using the composition is provided. The composition comprises a biodegradable acellular matrix, and passaged autologous fibroblasts substantially free of immunogenic proteins, e.g., culture medium serum-derived proteins, integrated within the matrix. Also provided is an injectable composition comprising an acellular filler material (e.g., any type of collagen) and passaged autologous fibroblasts substantially free of immunogenic proteins, e.g., culture medium serum-derived proteins, for correcting defects in skin, such as wrinkles or scars, and for augmenting tissue in the subject, particularly facial tissue.

Abstract: The present invention is directed to medical devices or pharmaceutical composition, each containing a synthetic, biodegradable, biocompatible polymer that is the reaction product of a polybasic acid or derivative thereof, a monoglyceride, and a cationic polyol.

Abstract: A semi-solid delivery vehicle contains a polyorthoester and an excipient, and a semi-solid pharmaceutical composition contains an active agent and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed.

Abstract: The present invention provides improved devices and methods for minimizing and/or inhibiting restenosis and hyperplasia after intravascular intervention. In particular, the present invention provides luminal prostheses which allow for programmed and controlled mycophenolic acid delivery with increased efficacy to selected locations within a patient's vasculature to inhibit restenosis. An intraluminal delivery prosthesis may comprise an expansible structure and means on or within the structure for releasing mycophenolic acid at a rate selected to inhibit smooth muscle cell proliferation.

Abstract: A composition for delivery of a therapeutic agent is provided. The composition comprises: (a) a biocompatible block copolymer comprising one or more elastomeric blocks and one or more thermoplastic blocks and (b) a therapeutic agent, wherein the block copolymer is loaded with the therapeutic agent. The block copolymer is preferably of the formula X—(AB)n, where A is an elastomeric block, B is a thermoplastic block, n is a positive whole number and X is a seed molecule. The elastomeric blocks are preferably polyolefin blocks, and the thermoplastic blocks are preferably selected from vinyl aromatic blocks and methacrylate blocks. According to another aspect of the invention, a medical device is provided, at least a portion of which is insertable or implantable into the body of a patient. The medical device comprises (a) the above biocompatible block copolymer and (b) a therapeutic agent, wherein the block copolymer is loaded with the therapeutic agent.

Abstract: An implantable or insertable medical device is provided which comprises (a) a superoxide dismutase mimic and (b) a polymeric release region. Upon administration to a patient, the polymeric release region controls the release of the superoxide dismutase mimic, which is beneficially selected from a metal-chelate superoxide dismutase mimic and a nitroxide superoxide dismutase mimic. Also provided is a method of making an implantable or insertable medical device.

Abstract: A method of tissue repair is provided using a biocompatible nonimmunogenic adhesive composition. The adhesive composition comprises collagen and a plurality of crosslinkable components having reactive functional groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. Kits for use in carrying out the method of the invention are also provided, as are pretreated surgically acceptable patches that have been coated with the aforementioned adhesive composition.

Abstract: A coil for locally dispensing medication to mammalian tissue is provided. The coil is formed from a length of flexible tubing sealed at opposite ends and containing a medication absorbable into tissue. The tubing walls are semi-permeable to the medication when the coil is in use, but impermeable during storage when the coil is not in use. The permeability of the coil tubing may be controlled either by the application and removal of a water-dissolvable surface coating or envelope, or by the control of an external condition such as temperature. The coil quickly and efficiently delivers a high concentration of medication to tissue in need of treatment, and is particularly useful in the treatment of prostatitis.

Abstract: A medical device is designed to be placed in a patient's body and release one or more therapeutic agents therefrom. The medical device includes an elongated member defining a passage for passing bodily fluids therethrough and at least one enclosed internal space for containing one or more therapeutic agents therein. The elongated member may further define one or more pores in fluid communication with the enclosed internal space. The medical device can deliver one or more therapeutic agents at a desired level or volume, over a desired period of time, and from a desired location of the device. Therapeutic agents may be released through the body of the medical device by diffusion and/or through the one or more pores.

Abstract: The present invention is directed to an improved sustained release drug delivery device comprising a drug core, a unitary cup, and a permeable plug.

Abstract: Pharmaceutical compositions that enable the release of a physiologically active substance over a prolonged period of time following administration to a patient are described. The pharmaceutical compositions are provided by encapsulation of a physiologically active substance into a matrix comprising biodegradable polymers and lipids. The rate of release of the physiologically active substance from the pharmaceutical composition is controlled by varying the ratio of the polymer to the lipid. The compositions can be stored in an aqueous suspension or as a solid dosage form. The physiologically active substances include small molecules, peptides, proteins, nucleic acids and vaccines. The biodegradable polymers include homopolymers, or random or block copolymers. The lipids include phospholipids, cholesterol and glycerides.

Abstract: A semi-solid delivery vehicle contains a polyorthoester and an excipient, and a semi-solid pharmaceutical composition contains an active agent and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed.

Abstract: A composite product is disclosed as a collagen support comprising at least one porous collagen layer covered on at least one side with an essentially compact collagen membrane consisting either of a collagen film prepared by drying a collagen gel, preferably in air or a gaseous fluid, or of a very highly compressed collagen sponge. At least one of the two layers, i.e. the porous layer and the essentially compact membrane, may comprise normal, genetically modified or malignant living cells originating particularly from young or elderly subjects. This composite product is used as a collagen support for the manufacture of artificial skin intended especially for performing in vitro tests on the efficacy of potentially active substances or for reconstructing damaged areas of skin in vivo.

Abstract: Implantable medical devices are provided for controlled release of drugs. In one embodiment, the device comprises a support structure; two or more discrete reservoirs provided in spaced positions across at least one surface of the support structure; and a release system loaded in each of the reservoirs, the release system including drug molecules dispersed in a degradable matrix material, wherein release of the drug molecules from the reservoir is controlled by in vivo disintegration of the matrix material. In another embodiment, the device comprises a support structure; two or more discrete reservoirs provided in spaced positions across at least one surface of the support structure; and a release system loaded in each of the reservoirs, the release system including drug molecules dispersed in a non-degradable matrix material, wherein release of the drug molecules from the reservoir is controlled by in vivo diffusion of the drug molecules from the matrix material.

Abstract: An increase in agent residence time at a tissue site is provided for by the presence of a barrier. The barrier is a separate entity from the agent when introduced to the tissue. A binding member is included in the barrier for coupling the barrier to the surface of the tissue. In one embodiment, agent is introduced to the tissue prior to attachment of the barrier to the tissue. In another embodiment, agent is presented after the barrier is positioned on the tissue surface. A delivery vehicle may be used to administer the agent and barrier to a patient.

Abstract: The invention features methods of making living tissue constructs having a predetermined shape by providing a negative mold having a defined shape; suspending isolated tissue precursor cells in a hydrogel to form a liquid hydrogel-precursor cell composition; introducing the liquid hydrogel-precursor cell composition into the mold; inducing gel formation to solidify the liquid hydrogel-precursor cell composition to form a living tissue construct; and removing the living tissue construct from the mold after gel formation.

Abstract: The present invention is directed to a flowable composition that is suitable for use as a controlled release implant. The flowable composition includes a biodegradable thermoplastic polyester that is at least substantially insoluble in aqueous medium or body fluid. The flowable composition also includes a biocompatible polar aprotic solvent. The biocompatible polar aprotic solvent is miscible to dispersible in aqueous medium or body fluid. The flowable composition also includes leuprolide acetate.

Abstract: Embodiments of the invention provide polymer coated implantable medical devices having a bioactive material posited in or on at least a portion of the coating layer, wherein the coating layer provides for the controlled release of the bioactive material from the coating layer. Preferably, the medical device is an intravascular stent.

Abstract: A hydroxyapatite based bioresorbable material is incorporated with anti-cancer agents to form an implant used for treatment against cancer. Sustained release of the anti-cancer agents may be achieved after implantation at the targeted sites. The dosage of the anti-cancer agent, the microstructure, morphology, and composition of the bioresorbable material allow control of the release profile. The invented implant may be used for drug delivery, chemotherapy, or gene therapy.

Abstract: Controllably dissolvable silica-xerogels prepared via sol-gel process and their use. A delivery device including controllably dissolvable silica-xerogel into which structure a biologically active agent is incorporated. Pharmaceutical preparations including this device. Medical devices for orthopedic and surgical purposes which contain controllably dissolvable silica-xerogels, which may further include a biologically active agent.

Abstract: A porous three-dimensional tissue repair matrix is provided which is biodegradable. The matrix is preferably formed from mineralized collagen where the mineral comprises particulate calcium phosphate immobilized in the matrix.

Abstract: The present invention relates to a sustained release preparation of a lipophilic drug, comprising a drug dispersion wherein the lipophilic drug and a water-soluble substance are dispersed, in a solid state at the body temperature of an animal or a human being to which the preparation is to be administered, in a water-impermeable and biocompatible material.

Abstract: The present invention relates to the discovery that biocompatible anionic polymers can effectively inhibit fibrosis, scar formation, and surgical adhesions. The invention is predicated on the discovery that anionic polymers effectively inhibit invasion of cells associated with detrimental healing processes, and in particular, that the effectiveness of an anionic polymer at inhibiting cell invasion correlates with the anionic charge density of the polymer. Thus the present invention provides a large number of materials for use in methods of inhibiting fibrosis and fibroblast invasion. Anionic polymers for use in the invention include but are not limited to natural proteoglycans, and the glycosaminoglycan moieties of proteoglycans. Additionally, anionic carbohydrates and other anionic polymers may be used. The anionic polymers dextran sulfate and pentosan polysulfate are preferred. In a more preferred embodiment, dextran sulfate, in which the sulfur content is greater than about 10% by weight, may be used.

Abstract: An implant, usually a stent, has a coating of a cross-linked water swellable polymer matrix preferably having a dry thickness of at least 0.1 &mgr;m, and a pharmaceutically active compound, the polymer having pendant cationic and pendant zwitterionic groups. The active is usually an anionic compound such as a nucleic acid. The polymer is peferably formed from 2-methacyloyloxyethyl-2′-trimethylammoniumethyl phosphate inner salt, trialkylammoniumalkyl(meth)acrylate and a cross-linkable monomer such as &ohgr;(trialkoxysilyl)alkyl(meth)acrylate, optionally with a termonomer such as a higher alkyl(meth)acrylate. The stent is coated with polymer, cross-linked then contacted with a solution or dispersion of active compound in a solvent which swells the polymer wehereby the active is absorbed into the polymer matrix. The stent is delivered by usual means into a body lumen and the active is released over an extended period of time into the wall of the lumen and/or fluid flowing therein.

Abstract: Bioabsorbable biocompatible polymers which provide a good match between their properties and those of certain tissue structures are provided. The bioabsorbable biocompatible polymers can be prepared with tensile strengths, elongation to breaks, and/or tensile modulus (Young's modulus) values of the tissues of the cardiovascular, gastrointestinal, kidney and genitourinary, musculoskeletal, and nervous systems, as well as those of the oral, dental, periodontal, and skin tissues. Methods for processing the bioabsorbable biocompatible polymers into tissue engineering devices are also provided.

Abstract: An implant device is provided which incorporates a retinoid for improving the biocompatibility of the device in tissue. The device may be bioerodible for the purpose of systemically or locally releasing a therapeutic agent in tissue or it may be a permanent implant which includes a surface treated with a retinoid for increasing the biocompatibility thereof.

Abstract: Controlled release of hydrophobic bioactive substances in vivo over an extended time period and without “bursts” of drug release is achieved using a liquid polymeric composition including a polymer such as poly(lactide-co-glycolide) copolymer in a mixture of hydrophilic and lipophilic solvents.

Abstract: The present invention features devices and methods for delivery of drug to an internal organ surface by delivery of drug directly to the surface of the organ such that the drug traverses the organ surface and enters the organ tissue. The device is in the form of an implantable drug delivery patch comprising a first layer, which is generally substantially drug-impermeable. When the first layer is placed on an outer surface of an organ, a drug reservoir is defined by the first layer and the organ surface.

Abstract: A composition and method for suppressing pain and irritation of tissue uses an anti-irritant in an effective amount to suppress pain and irritation temporarily when applied topically to the skin, mucosa, or the eye. The anti-irritant is a natural or non-nutritive sweetener. The composition can contain an edible acid such as citric acid and ascorbic acid from fresh lemon juice to provide a pH of about 2.0 to 4.0 and an anti-irritant, such as sodium saccharine. The composition can be used to treat cuts, scratches and abrasions on the skin and for applying a pharmaceutical agent to the skin, mucosa or eye without irritation. The acidic composition can further be used to remove or loosen calculus deposits from the teeth without burning or irritation of the gums.

Abstract: The present invention provides high mechanical strength amphiphilic polymeric networks and implantable biological devices made therefrom that are capable of encasing and, thus, immunoisolating biological material from an immunological response of a host individual. The present invention also provides methods for making the amphiphilic networks and implantable biological devices. The present invention also provides a method for the treatment of type I diabetes mellitus comprising the steps of encasing a sufficient amount of islet of Langerhans cells within said biological device, wherein said biological device is capable of immunoisolating said encased islet cells upon implantation into an individual; implanting said biological device into a diabetic host individual; allowing said implanted biological device to remain implanted in said diabetic individual for a time sufficient to normalize the blood glucose level in said diabetic individual.

Abstract: A fluid matrix comprising cross-linked remodelable collagen from a donor vertebrate animal is useful for regenerating hydrodynamic function in damaged intervertebral discs in vivo. The matrix may be injectable and may comprise cells and a plurality of purified cell growth factors. The matrix promotes cell growth and elaboration of proteoglycans to facilitate regeneration of native tissues. The collagen in the matrix may be cross-linked using photooxidative catalysis and visible light, and purified cell growth factors are preferably at least partly bone-derived.

Abstract: The present invention provides compositions comprising biologically-active somatotropin formulated for extended release and methods of preparing and methods of using the same. These compositions comprise somatotropin, at least a first bioavailability-enhancing constituent (BEC), and a substantially non-aqueous, hydrophobic excipient, and optionally a second BEC. The first BEC is typically a surfactant (preferably a non-ionic surfactant) or a cyclodextrin compound. The optional second BEC may comprise (i) amino acids or amino acid derivatives; (ii) hydroxamate derivatives; (iii) non-reducing carbohydrates; (iv) oxo-acid salts; or (v) a mixture of two or more compounds from within the foregoing classes (i)-(iv).