Diffusion Barrier Is Matrix Patents (Class 424/425)
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Patent number: 7090867Abstract: The present invention provides a controlled release device for sustained or pulsatile delivery of pharmaceutically active substances for a predetermined period of time. This invention further provides such device in which sustained or pulsatile delivery is obtained by the unique blend and intimate mixture of pharmaceutically active substances with a microbial polysaccharide and uncrosslinked linear polymer and optionally a crosslinked polymer and/or lipophillic polymer and/or saturated polyglycolyzed glyceride. The invention also provides a process for the manufacture of such devices and pharmaceutical compositions containing the same.Type: GrantFiled: May 15, 2003Date of Patent: August 15, 2006Assignee: Intellipharmaceutical Corp.Inventors: Isa Odidi, Amina Odidi
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Patent number: 7045142Abstract: 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.Type: GrantFiled: September 27, 2004Date of Patent: May 16, 2006Assignee: Boston Scientific Scimed, Inc.Inventor: Robert A. Herrmann
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Patent number: 7041308Abstract: The present invention provides a system for treating a vascular condition, including a catheter, a stent coupled to the catheter, a polymeric coating on the stent including a segmented homochain copolyester, and a bioactive drug dispersed within the polymeric coating.Type: GrantFiled: March 20, 2003Date of Patent: May 9, 2006Assignee: Poly-Med, Inc.Inventors: Shalaby W. Shalaby, Todd Campbell
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Patent number: 7041309Abstract: An improved technique for spinal fusion including administration of an HMG-CoA reductase inhibitor to the fusion site. The HMG-CoA reductase inhibitor is preferably delivered to the site by a carrier. More preferably, the HMG-CoA reductase inhibitor is delivered to the site by a noncompressible delivery vehicle. The invention is suitable for promoting non-anatomic or heterotopic bone growth between any bony surfaces where bone growth is desired but does not naturally occur.Type: GrantFiled: October 28, 2002Date of Patent: May 9, 2006Assignee: NeuroPro Technologies, Inc.Inventors: Benjamin J. Remington, David J. Bearss, Kavian Shahi
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Patent number: 7025982Abstract: A process for fabricating a medical assembly having a medical device at least a portion of which is formed of inorganic material is provided. The medical assembly is suitable for substantially long-term implantation in a host animal. The process includes modifying a surface of the medical device to form a hydrophilic adhesion-promoting surface. The hydrophilic adhesion-promoting surface is coated with an alginate solution comprising alginate and the alginate is reacted with alkaline earth metal cations.Type: GrantFiled: September 19, 2002Date of Patent: April 11, 2006Assignee: Medtronic, Inc.Inventors: Michael F. Mattes, Alvin Rhorer
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Patent number: 7025997Abstract: The present invention relates to plant extracts containing a monomenthyl succinate for use as a coolant in food and non-food products. Methods for isolating the plant extracts are also provided.Type: GrantFiled: September 24, 2003Date of Patent: April 11, 2006Assignee: International Flavors & Fragrances Inc.Inventors: Richard Dwyer Hiserodt, Thumplasseril V. John, Jide Adedeji, Markus A. Eckert
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Patent number: 7022343Abstract: Methods for the simple, reliable application and local controlled release of selected anti-arrhythmia drugs from a hydrogel applied to or polymerized on the tissues of the heart or its vessels, especially in conjunction with cardiac bypass or other cardiac surgery, have been developed. The anti-arrhythmia drugs are incorporated into hydrogels that biodegrade and adhere to the tissues to which the anti-arrhythmic drugs are to be delivered. The hydrogels may be formed in vitro or in vivo. In a preferred embodiment, the drugs are effective to lengthen atrial effective refractory period. A particularly preferred drug is amiodarone.Type: GrantFiled: December 27, 2001Date of Patent: April 4, 2006Assignee: Genzyme CorporationInventors: C. Michael Philbrook, James W. Burns, Kevin C. Skinner, Robert J. Miller
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Patent number: 7022334Abstract: 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.Type: GrantFiled: March 20, 2002Date of Patent: April 4, 2006Assignee: Advanced Cardiovascular Systems, Inc.Inventor: Ni Ding
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Patent number: 6976981Abstract: 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.Type: GrantFiled: May 17, 2001Date of Patent: December 20, 2005Assignee: Alza CorporationInventor: Rupal Ayer
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Patent number: 6974679Abstract: The invention relates to a method of in vitro testing of the efficacy of a potentially active substance comprising monitoring the effect of said potentially active substance on an artificial skin, comprising a composite product forming a collagen support comprising at least one porous collagen layer covered on at least one side with a collagen membrane component selected from the group consisting of a collagen membrane prepared by compression of a collagen sponge at a pressure of at least about 50 bar and of a collagen membrane comprising a collagen film prepared by drying a collagen gel separately from the porous collagen layer, thereby providing a reliable method for finding new potentially active substances.Type: GrantFiled: February 10, 2003Date of Patent: December 13, 2005Assignee: ColeticaInventors: Valerie Andre, Nabil Abdul Malak, Alain Huc
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Patent number: 6960351Abstract: 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.Type: GrantFiled: July 21, 2003Date of Patent: November 1, 2005Assignee: Brown University Research FoundationInventors: Keith E. Dionne, Dwaine F. Emerich, Diane Hoffman, Paul R. Sanberg, Lisa Christenson, Orion D. Hegre, David W. Scharp, Paul E. Lacy, Patrick Aebischer, Alfred V. Vasconcellos, Michael J. Lysaght, Frank T. Gentile
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Patent number: 6939557Abstract: 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.Type: GrantFiled: August 26, 2003Date of Patent: September 6, 2005Assignee: Azopax Therapeutics LLCInventors: Stephen C. Rowe, Kalvin Yim, Beadle P. Retnarajan, Jeffrey A. Hubbell, Durga Annavajula
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Patent number: 6936278Abstract: 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.Type: GrantFiled: June 6, 2002Date of Patent: August 30, 2005Assignee: Jagotec AGInventors: Mats Reslow, Monica Jönsson, Karin Larsson, Timo Laakso
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Patent number: 6923990Abstract: 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.Type: GrantFiled: April 23, 2003Date of Patent: August 2, 2005Inventor: Christopher Capelli
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Patent number: 6913767Abstract: Methods and compositions are provided for the encapsulation of antigens in PLGA microspheres for use as vaccines. Such microspheres can also contain adjuvants. Mixtures of microspheres are provided which release antigen at desired intervals to provide boosts with antigen.Type: GrantFiled: April 30, 1997Date of Patent: July 5, 2005Assignee: Genentech, Inc.Inventors: Jeffrey L. Cleland, Amy Lim, Michael Frank Powell
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Patent number: 6899887Abstract: 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.Type: GrantFiled: May 17, 2001Date of Patent: May 31, 2005Assignee: Micron Technology, Inc.Inventor: Rupal Ayer
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Patent number: 6896894Abstract: 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.Type: GrantFiled: October 30, 2001Date of Patent: May 24, 2005Assignee: Battelle Memorial InstituteInventors: Richard S. Brody, Sreedhara Alavattam
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Patent number: 6869443Abstract: A stent includes a main body of a generally tubular shape for insertion into a lumen of a vessel of a living being. The tubular main body includes a substantially biodegradable matrix having collagen IV and laminin that enclose voids within the matrix. The tubular main body also includes a biodegradable strengthening material in contact with the matrix to strengthen the matrix. The tubular main body is essentially saturated with drugs.Type: GrantFiled: March 28, 2002Date of Patent: March 22, 2005Assignee: SciMed Life Systems, Inc.Inventors: Paul J. Buscemi, Elizabeth A. Stejskal, Donald F. Palme, II, Lixiao Wang
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Patent number: 6863899Abstract: Shaped, composite bodies are provided. One portion of the shaped bodies comprises an RPR-derived porous inorganic material, preferably a calcium phosphate. Another portion of the composite bodies is a different solid material, preferably metal, glass, ceramic or polymeric. The shaped bodies are especially suitable for orthopaedic and other surgical use.Type: GrantFiled: June 7, 2002Date of Patent: March 8, 2005Assignee: Vita Special Purpose CorporationInventors: Antony Koblish, Ronald Sapieszko, David Dychala, Erik Erbe
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Patent number: 6861068Abstract: 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.Type: GrantFiled: January 26, 2004Date of Patent: March 1, 2005Assignee: A.P. Pharma, Inc.Inventors: Steven Y. Ng, Hui-Rong Shen, Jorge Heller
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Patent number: 6858221Abstract: 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.Type: GrantFiled: September 11, 2002Date of Patent: February 22, 2005Assignee: Avantec Vascular CorporationInventors: Motasim Sirhan, John Yan
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Patent number: 6835387Abstract: 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.Type: GrantFiled: June 11, 2002Date of Patent: December 28, 2004Assignee: SciMed Life Systems, Inc.Inventor: Robert A. Herrmann
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Patent number: 6818224Abstract: A method is described for preparing a fluid pharmaceutical composition which allows the controlled release of at least one active substance. The method involves mixing a therapeutically effective amount of at least one active substance, from 3 to 55% by weight of phospholipid, from 16 to 72% by weight of pharmaceutically acceptable solvent, and from 4 to 52% by weight of fatty acid. The composition has a property of gelling instantaneously in the presence of an aqueous phase.Type: GrantFiled: September 17, 2002Date of Patent: November 16, 2004Assignee: UCB, S.A.Inventors: Domenico Fanara, Henri Vranckx, Michel Deleers, Pierre Grognet
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Publication number: 20040220665Abstract: A coating and a method of coating an implantable medical device, such as a stent, is disclosed. The method includes subjecting the coating to a thermal condition which can result in reduction of the rate of release of an active agent from the coating subsequent to the implantation of the device.Type: ApplicationFiled: June 25, 2003Publication date: November 4, 2004Inventors: Syed F.A. Hossainy, Fuh-Wei Tang, Stephen D. Pacetti, Jeff Royal, Dorie M. Happ, Kurt Scheinpflug, Ty Hu
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Publication number: 20040208985Abstract: An implant having a coating comprising a polymer matrix is swollen in a pharmaceutical solution whereby pharmaceutically active compound is imbibed into the polymer matrix. When the product is implanted, release of the pharmaceutically active compound from the coating takes place. The polymer is preferably formed from ethylenically unsaturated monomers including a zwitterionic monomer, most preferably 2-methacryloyloxyethyl-2′-trimethylammoniumethylphosphate inner salt. The monomers from which the polymer is formed may further include surface binding monomers, such as hydrophobic group containing monomers, and crosslinkable monomers, the content of which may be used to control the swellability. Preferably the implant is a stent and the coating of polymer on the exterior wall surface is thicker than the coating of polymer on the interior surface. Release of the drug may be controlled by selection of comonomers. The implant is suitably a stent for use in the cardiovascular system.Type: ApplicationFiled: May 11, 2004Publication date: October 21, 2004Applicant: BIOCOMPATIBLES UK LIMITEDInventors: Lee Rowan, Peter William Stratford, Alistair Stewart Taylor, Terrence Albert Vick
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Publication number: 20040193255Abstract: The present invention relates to implantable medical devices for the localized delivery of therapeutic agents, such as drugs, to a patient. More particularly, the invention relates to a device having a gradient of water soluble therapeutic agents within a therapeutic agent layer and a mixing layer that allows for controlled release of the therapeutic agents.Type: ApplicationFiled: March 28, 2003Publication date: September 30, 2004Inventors: John F. Shanley, Theodore L. Parker
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Patent number: 6793938Abstract: 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.Type: GrantFiled: May 17, 2001Date of Patent: September 21, 2004Assignee: Skye Pharma, Inc.Inventor: Mantripragada Sankaram
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Patent number: 6790454Abstract: 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.Type: GrantFiled: July 14, 2000Date of Patent: September 14, 2004Assignee: ColeticaInventors: Nabil Abdul Malak, Valérie Andre, Alain Huc
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Patent number: 6790458Abstract: 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.Type: GrantFiled: April 7, 2003Date of Patent: September 14, 2004Assignee: AP Pharma Inc.Inventors: Steven Y. Ng, Hui-Rong Shen, Jorge Heller
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Publication number: 20040176749Abstract: The invention relates to an insert for the treatment of dry eyes, wherein the insert can be placed on or inserted into the lacrimal sac or the cornea.Type: ApplicationFiled: January 7, 2004Publication date: September 9, 2004Inventors: Chris P Lohmann, Achim Goepferich
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Patent number: 6773713Abstract: 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.Type: GrantFiled: February 21, 2002Date of Patent: August 10, 2004Assignee: University of MassachusettsInventors: Lawrence J. Bonassar, Jon A. Rowley, David J. Mooney
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Patent number: 6770729Abstract: 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.Type: GrantFiled: September 30, 2002Date of Patent: August 3, 2004Assignee: Medtronic MiniMed, Inc.Inventor: William P. Van Antwerp
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Patent number: 6767550Abstract: 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.Type: GrantFiled: June 30, 2000Date of Patent: July 27, 2004Assignee: Berkeley Advanced Biomaterials, Inc.Inventors: François Y. Génin, Ping Luo, Alekha K. Dash
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Patent number: 6767551Abstract: The inventive coating may be employed to deliver a pharmaceutical agent to a selected body area that is involved within the insertion or application of a medical device. Such medical devices may include silicone based urinary catheters and other medical implants as well as other silicone based devices having deformable portions which could benefit from the release of a pharmaceutical agent from its surface. The coating allows the introduction of the pharmacological additive having a release rate that is within acceptable pharmacokinetic criteria. The release rate is adjusted by utilizing different salt forms of the additive and adjusting the concentration of urethane and RTV silicone. The coating incorporates additive compounds such as anti-microbial, anti-fungals and other organic compounds. Methods are also provided for the manufacture of the subject coating and for the application of the same to surfaces of medical devices.Type: GrantFiled: August 15, 2001Date of Patent: July 27, 2004Assignee: Sherwood Services AGInventors: Diane McGhee, Scott M. Britton, Elizabeth Lagwinska
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Patent number: 6764517Abstract: 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.Type: GrantFiled: February 22, 2002Date of Patent: July 20, 2004Assignee: DePuy AcroMed, Inc.Inventors: Ronald K. Yamamoto, Michael K. Kwan, Stephen D. Pacetti
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Patent number: 6764690Abstract: 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.Type: GrantFiled: June 25, 2002Date of Patent: July 20, 2004Assignee: DelSiTech OyInventors: Manja Ahola, Heidi Fagerholm, Ilkka Kangasniemi, Juha Kiesvaara, Pirjo Kortesuo, Kauko Kurkela, Niilo Saarinen, Antti Yli-Urpo
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Patent number: 6756362Abstract: 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.Type: GrantFiled: May 6, 2002Date of Patent: June 29, 2004Inventors: Dikla Roufa, Adrian Harel, Robert C. A. Frederickson, George T. Coker, III
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Publication number: 20040116958Abstract: The invention relates to a spacing device (stent) for use in fenestrations of the paranasal sinus. Said device consists of a sheath which forms a hollow body, surrounding an internal cavity. An active substance, which is released in a controlled manner by the spacing device, is contained in the sheath or in at least one layer of the sheath. The relationship q of the external diameter of the hollow body to the internal diameter of the hollow body is expressed by 1.2≦q≦3.0.Type: ApplicationFiled: February 4, 2004Publication date: June 17, 2004Inventors: Achim Gopferich, Werner Hosemann
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Patent number: 6746685Abstract: 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.Type: GrantFiled: November 6, 2002Date of Patent: June 8, 2004Assignee: Tepha, Inc.Inventor: Simon F. Williams
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Patent number: 6746686Abstract: 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.Type: GrantFiled: September 24, 2001Date of Patent: June 8, 2004Assignee: Biocompatibles UK LimitedInventors: Laurence Gerald Hughes, Terrence Albert Vick, Jin Hai Wang
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Patent number: 6733767Abstract: 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.Type: GrantFiled: March 18, 1999Date of Patent: May 11, 2004Assignee: Merck & Co., Inc.Inventors: Rey T. Chern, Joel R. Zingerman
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Patent number: 6733530Abstract: Autologous cultured keratinocytes are grown on a biosynthetic and biocompatible substratum following pre-seeding with autologous or allogenic dermal fibroblasts. The resultant composite material may then be applied on the neodermis of artificial skin which had been previously engrafted on the patient. The composite material, and specifically Composite Biocompatible Skin Graft (CBSG) material comprises autologous keratinocytes A and allogenic or autologous dermal fibroblasts grown on an artificial skin. A method for cultivating the CBSG includes the application of dermal fibroblasts onto the substratum as a feeder layer and then the inoculation of autologous keratinocytes on the resultant structure. A method for engraftment comprises first applying an artificial skin with a protective silicone membrane on a wound area, thereby allowing vascularization; and following vascularization, removing the silicone membrane and engrafting the CBSG material onto the vascularized artificial skin.Type: GrantFiled: August 2, 1999Date of Patent: May 11, 2004Inventors: Ping Kuen Lam, Eric Sun-Yin Chan
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Patent number: 6730315Abstract: A cell culture medium and hydrogel matrix for long term storage and proliferation of cells is provided. The cell culture medium and hydrogel matrix include an effective amount of polar amino acids, the polar amino acids selected from the group consisting of arginine, lysine, histidine, glutamic acid, and aspartic acid. The cell culture medium comprises about 5 to about 150 mM of polar amino acids. The hydrogel matrix comprises about 3 to about 150 mM of polar amino acids. Arginine and glutamic acid are preferably supplemented in the cell culture medium. Arginine, lysine, and glutamic acid are preferably supplemented in the hydrogel matrix. A method of maintaining viability and functioning of a transplant is also provided. The method of maintaining viability of a transplant includes encapsulating the cells in a hydrogel matrix and injecting the encapsulated cells into the host organism.Type: GrantFiled: January 11, 2001Date of Patent: May 4, 2004Assignee: Encelle, Inc.Inventors: Anton-Lewis Usala, Richard Chris Klann
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Patent number: 6726920Abstract: 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.Type: GrantFiled: September 22, 2000Date of Patent: April 27, 2004Assignee: Durect CorporationInventors: Felix Theeuwes, Timothy S. Nelson
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Patent number: 6723335Abstract: 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.Type: GrantFiled: April 7, 2000Date of Patent: April 20, 2004Inventors: Jeffrey William Moehlenbruck, John Paul Ranieri
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Patent number: 6713081Abstract: Ocular implant devices for the delivery of a therapeutic agent to an eye in a controlled and sustained manner. Dual mode and single mode drug delivery devices are illustrated and described. Implants suitable for subconjunctival placement are described. Implants suitable for intravitreal placement also are described. The invention also includes fabrication and implementation techniques associated with the unique ocular implant devices that are presented herein.Type: GrantFiled: March 15, 2001Date of Patent: March 30, 2004Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Michael R. Robinson, Karl G. Csaky, Peng Yuan, Cynthia Sung, Robert B. Nussenblatt, Janine A. Smith
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Patent number: 6713079Abstract: The present invention provides a method of stimulating vascularization at a site in a mammal, said method comprising contacting said site with a matrix comprising gelatin and a nitric oxide inhibitor. The gelatin is preferably denatured collagen. The nitric oxide inhibitor may be a sulfonated moiety. The inhibitor may be an L-arginine analog, such as aminoguanidine, N-monoethyl L-arginine, N-nitro-L-arginine and D-arginine. The matrix may further comprise a nitric oxide scavenger, such as dextran, heparin, cysteine and cystine.Type: GrantFiled: January 19, 2001Date of Patent: March 30, 2004Assignee: Encelle, Inc.Inventor: Anton-Lewis Usala
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Patent number: 6706274Abstract: This invention relates to devices and methods for the local, differential delivery of nitric oxide within the body. The devices include devices having at least two differing nitric oxide donor compounds, such as nitric oxide donor compounds having differing half-lives and nitric oxide donor compounds having different release mechanisms. The devices also include devices having at least two chemically distinct compositions to which nitric oxide donor compounds are adsorbed or attached or within which the donor compounds are disposed. The devices are typically used to increase local nitric oxide concentration in the body upon placement of the medical article at a delivery position on or within a patient.Type: GrantFiled: January 18, 2001Date of Patent: March 16, 2004Assignee: SciMed Life Systems, Inc.Inventors: Robert A. Herrmann, David Knapp
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Patent number: 6699504Abstract: 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.Type: GrantFiled: January 29, 2001Date of Patent: March 2, 2004Assignee: Pelias Technologies, Inc.Inventors: Stephen C. Rowe, Kalvin Yim, Beadle P. Retnarajan, Jeffrey A. Hubbell, Durga Annavajula
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Patent number: 6699484Abstract: An especially useful fibrin glue composition comprises a biocompatible, bioabsorbable hyaluronic acid derivative material, upon which are applied or chemically bonded fibrinogen and thrombin, along with other optional constituents, such as additional coagulation factors, anti-fibrinolytics, stabilizers and biologically active substances. The fibrinogen, thrombin and other components can take the form of a dry preparation, an aqueous or nonaqueous preparation, or as a combination thereof. Such a fibrin glue composition can be placed directly on a wound site and is fully reabsorbed into the body.Type: GrantFiled: January 6, 2003Date of Patent: March 2, 2004Assignee: Haemacure CorporationInventors: Elaine Whitmore, Marc R. Paquin