Microcapsule-sustained Or Differential Release Patents (Class 514/963)
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Patent number: 5843509Abstract: Stabilization of colloidal systems through the formation of lipid-polyssacharide complexes. Development of a procedure for the preparation of colloidal systems involving a combination of two ingredients: a water soluble and positively charged polyssacharide and a negatively charged phospholipid. Colloidal systems (submicron emulsions and polymeric nanoparticles and nanocapsules) are stabilized through the formation, at the interface, of an ionic complex: aminopolyssachride-phospholipid. These colloidal systems are characterized by their positive charge and their improved stability. Furthermore, they can be freeze-dried, stored in a dry state and hydrated when required. They can be interesting systems for the administration of drugs by the oral, transdermal, ocular, nasal and vaginal routes of administration. In addition, they can be of interest for cosmetic use.Type: GrantFiled: February 27, 1997Date of Patent: December 1, 1998Assignee: Universidade de Santiago de CompostelaInventors: Pilar Calvo Salve, Maria Jose Alonso Fernandez, Carmen Remunan Lopez, Jose Luis Vila Jato
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Patent number: 5837747Abstract: The present invention relates to a new form of biocompatible materials (e.g., lipids, polycations, polysaccharides) which are capable of undergoing free radical polymerization, e.g., by using certain sources of light; methods of modifying certain synthetic and naturally occurring biocompatible materials to make polymerizable microcapsules containing biological material coated with said polymerizable materials, composites of said polymerizable materials, methods of making microcapsules and encapsulating biological materials therein, and apparatus for making microcapsules containing biological cells (particularly islets of Langerhans) coated with polymerizable alginate or with a composite thereof (e.g., alginate and PEG). The present invention also relates to drug delivery systems relating to the foregoing, as well as bioadhesives and wound dressings made utilizing the foregoing technology.Type: GrantFiled: April 28, 1994Date of Patent: November 17, 1998Assignee: VivoRx, Inc.Inventors: Patrick Soon-Shiong, Neil P. Desai, Paul A. Sandford, Roswitha A. Heintz, Soebianto Sojomihardjo
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Patent number: 5834023Abstract: A once-a-day controlled release diltiazem formulation is described which includes:(a) from 20 to 50% by weight of enteric polymeric membrane coated pellets comprising a polymer membrane coated core which comprises a biologically inert core which is coated with a first layer which consists essentially of diltiazem and a polymeric binder; and a second layer which comprises a membrane comprising a pH dependent polymeric material; and(b) from 50% to 80% by weight of delayed pulse polymeric membrane coated pellets comprising a polymeric membrane coated core which comprises a biologically inert core which is coated with a first layer which consists essentially of diltiazem and a polymeric binder and a second layer which comprises a polymeric membrane which will substantially maintain its integrity in the varying pH conditions of the gastrointestinal tract but is permeable to diltiazem; and(c) a unit dose containment system.Type: GrantFiled: July 9, 1996Date of Patent: November 10, 1998Assignee: Andrx Pharmaceuticals, Inc.Inventor: Chih-Ming Chen
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Patent number: 5824345Abstract: Compositions useful in the delivery of fragrances and flavorant active agents, and particularly vaporous fragrances and flavorants, are provided. These compositions include a microsphere which includes (a) the active agent; and (b) (i) a proteinoid, (ii) a modified hydrolyzed vegetable protein wherein the protein is modified with an amino reactive agent, or (iii) a combination thereof. Also contemplated is a method for preparing these compositions wherein the active agent is mixed with the proteinoid of hydrolyzed vegetable protein solution and the proteinoid or modified hydrolyzed vegetable protein is precipitated out of the solution, thereby forming a microsphere containing the active agent. In a further embodiment, the active agent is applied to a substrate.Type: GrantFiled: June 7, 1995Date of Patent: October 20, 1998Assignee: Emisphere Technologies, Inc.Inventor: Sam J. Milstein
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Patent number: 5820883Abstract: A method, and compositions for use therein capable, of delivering a bioactive agent to an animal entailing the steps of encapsulating effective amounts of the agent in a. biocompatible excipient to form microcapsules having a size less than approximately ten micrometers and administering effective amounts of the microcapsules to the animal. A pulsatile response is obtained, as well as mucosal and systemic immunity.Type: GrantFiled: June 6, 1995Date of Patent: October 13, 1998Assignees: Southern Research Institute, The UAB Research FoundationInventors: Thomas R. Tice, Richard M. Gilley, John H. Eldridge, Jay K. Staas
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Patent number: 5814344Abstract: A method, and compositions for use therein capable, of delivering a bioactive agent to an animal entailing the steps of encapsulating effective amounts of the agent in a biocompatible excipient to form microcapsules having a size less than approximately ten micrometers and administering effective amounts of the microcapsules to the animal. A pulsatile response is obtained, as well as mucosal and systemic immunity.Type: GrantFiled: June 6, 1995Date of Patent: September 29, 1998Assignees: Southern Research Institute, The UAB Research FoundationInventors: Thomas R. Tice, Richard M. Gilley, John H. Eldridge, Jay K. Staas
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Patent number: 5811128Abstract: A method, and compositions for use therein capable, of delivering a bioactive agent to an animal entailing the steps of encapsulating effective amounts of the agent in a biocompatible excipient to form microcapsules having a size less than approximately ten micrometers and administering effective amounts of the microcapsules to the animal. A pulsatile response is obtained, as well as mucosal and systemic immunity.Type: GrantFiled: September 7, 1993Date of Patent: September 22, 1998Assignees: Southern Research Institute, The UAB Research FoundationInventors: Thomas R. Tice, Richard M. Gilley, John H. Eldridge, Jay K. Staas
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Patent number: 5792795Abstract: Inflammatory bowel disease, especially Crohn's disease and ulcerative colitis, is treated by administration of an oral dosage form, containing as an active principle an omega-3 polyunsaturated acid in free acid form or as a pharmaceutically acceptable salt thereof, which releases the acid in the ileum. Preferably the oral dosage form is a gelatine capsule coated with a poly(ethylacrylate-methylmethacrylate).Type: GrantFiled: August 7, 1996Date of Patent: August 11, 1998Assignee: Tillotts Pharma AGInventors: Thomas Buser, Emilio P. Camporesi
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Patent number: 5785993Abstract: SOD and other active oxygen inhibitors are directly applied in combination with a barrier material at local sites of tissue injury to prevent or decrease formation of adhesions and undesirable proliferation of cells. Preferred barrier materials are polymeric hydrogels providing controlled release of AOI which are directly applied to the afflicted tissue. Examples demonstrate the effects of SOD on pelvic adhesions in the rat when administered by intraperitoneal (I.P.) bolus and by localized sustained release from a topically applied hydrogel system.Type: GrantFiled: July 29, 1996Date of Patent: July 28, 1998Assignee: Focal, Inc.Inventors: Keith Baker, Arthur J. Coury
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Patent number: 5780389Abstract: The present invention relates to microcapsules containing water-insoluble, liquid active ingredients or mixtures thereof, which are employed principally in the sector of plant protection and in which the solvent which is likewise present within the capsule is a liquid substance comprising two or more aromatic rings.The microencapsulation of plant protection agents, especially the envelopment of water-insoluble, liquid or solid active particles in water-based mixed-phase systems, has developed in recent years to become a standard formulation technique.Type: GrantFiled: September 26, 1995Date of Patent: July 14, 1998Assignee: Hoechst Schering AgrEvo GmbHInventors: Hans-Peter Krause, Thomas Maier, Jean-Paul Schoeni, Anna Waltersdorfer
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Patent number: 5780051Abstract: The present invention features methods and articles of manufacture for treating nicotine withdrawal symptoms and promoting smoking cessation. The methods and articles feature the administration of an effective amount of a nicotine substitute and monitor the presence of nicotine in the biological sample of such subject with a nicotine detection system.Type: GrantFiled: January 22, 1997Date of Patent: July 14, 1998Assignee: DynaGen, Inc.Inventors: Amruta R. Eswara, Neal Muni, F. Howard Schneider, Peter J. Mione
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Patent number: 5776495Abstract: A process for the production of a solid dispersion of at least one therapeutic agent in a hydrophilic carrier having enhanced solubility in an aqueous media comprising dissolving at least one therapeutic agent in a volatile organic solvent containing a very hydrophilic polymer and evaporating the solvent to dryness to form a co-precipitate of therapeutic agent and hydrophilic polymer and the resulting products and their therapeutic method of use.Type: GrantFiled: June 27, 1996Date of Patent: July 7, 1998Assignee: Laboratoires EffikInventors: Roselyne Duclos, Didier Terracol
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Patent number: 5753264Abstract: The invention relates to a process for preparing a chitosan-containing microcapsules and emulsions of an oil including the steps of (a) forming an oil-in-water emulsion by homogenizing said oil into an aqueous solution containing an anionic emulsifier; and (b) adding to the emulsion obtained in (a) an aqueous chitosan solution while continuously homogenizing the mixture to give a stable emulsion, which is converted into microcapsules by using the proper electrolyte and pH changes. Also encompassed are preparations including as active ingredient a lice repelling agent, vitamin E or a UV radiation photoprotectant. The preparations may be sustained-release or long acting preparations.Type: GrantFiled: December 26, 1995Date of Patent: May 19, 1998Assignee: Yissum Research Development Company of the Hebrew UniversityInventors: Shlomo Magdassi, Kosta Mumcuoglu, Uri Bach, Yulia Rosen
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Patent number: 5750147Abstract: Methods for preparing microspheres containing imidazole derivatives are provided. Also provided is the use of imidazole derivatives containing microspheres for treating fungal infections. Oral dosage forms for oral administration are also provided.Type: GrantFiled: June 7, 1995Date of Patent: May 12, 1998Assignee: Emisphere Technologies, Inc.Inventor: Martin L. Kantor
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Patent number: 5747060Abstract: A formulation for inducing sustained regional local anesthesia in a patient comprising a substrate comprising a local anesthetic and an effective amount of a biocompatible, biodegradable, controlled release material prolonging the release of the local anesthetic from the substrate to obtain a reversible nerve blockade when implanted or injected in a patient, and an amount of colchicine effective to prolong the duration of the local anesthesia for a time period longer than that obtainable from the substrate without colchicine.Type: GrantFiled: March 26, 1996Date of Patent: May 5, 1998Assignee: Euro-Celtique, S.A.Inventors: Richard Sackler, Paul Goldenheim, Mark Chasin
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Patent number: 5723269Abstract: A novel microparticle preparation comprising microparticles of a polymer which contain a drug and are at least partially or wholly coated with a water-soluble inorganic salt, a water-soluble organic acid or a water-soluble salt of an organic acid, which acts as an agent for preventing aggregation of the microparticle preparation is disclosed. The preparation is produced by spraying a polymer solution containing a drug and a solution or dispersion of a water-soluble inorganic salt, a water-soluble organic acid or a water-soluble salt of an organic acid from different nozzles and contacting them with each other in a spray dryer. In this procedure, if desired, a non-ionic surfactant may be added to the solution of the water-soluble inorganic salt, the water-soluble organic acid or the water-soluble salt of organic acid, or a solution of non-ionic surfactant may be sprayed from the other nozzle simultaneously.Type: GrantFiled: March 7, 1996Date of Patent: March 3, 1998Assignee: Takeda Chemical Industries, Ltd.Inventors: Yasaburo Akagi, Nobuyuki Takechi, Muneo Nonomura
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Patent number: 5718921Abstract: A method for preparation of biodegradable polymeric drug delivery devices using relatively low temperatures and non-aqueous solutions which is particularly useful with polyanhydrides, thermolabile drugs, and in forming multi-layered devices.In a first embodiment, the polymer is dissolved in a volatile organic solvent, the drug is dispersed or dissolved in the polymer solution, the mixture is suspended in an organic oil, and the organic solvent is extracted into the oil, creating microspheres. The preferred polymers are polyanhydrides since they are biodegradable and have been proven to be useful in vivo.In a second embodiment, the polymer is dissolved in organic solvent with or without the drug, and the mixture is suspended in glycerol. The suspension is frozen and the organic solvent slowly evaporated.Type: GrantFiled: August 2, 1996Date of Patent: February 17, 1998Assignee: Massachusetts Institute of TechnologyInventors: Edith Mathiowitz, Claudy J.P. Mullon, Abraham J. Domb, Robert S. Langer
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Patent number: 5716644Abstract: A composition, and methods of forming and using said composition, for the sustained release of non-aggregated, biologically active, erythropoietin (EPO). The sustained release composition of this invention comprises a polymeric matrix of a biocompatible polymer and particles of biologically active, aggregation-stabilized EPO, wherein said particles are dispersed within the biocompatible polymer.The method of the invention for producing a composition for the sustained release of biologically active EPO, includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, aggregation-stabilized EPO in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said EPO particles.The method for using a composition of the invention is a method for providing a therapeutically effective blood level of biologically active, non-aggregated erythropoietin in a subject for a sustained period.Type: GrantFiled: June 7, 1995Date of Patent: February 10, 1998Assignee: Alkermes, Inc.Inventors: Stephen E. Zale, Paul A. Burke, Howard Bernstein, Avram Brickner
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Patent number: 5716640Abstract: A method of producing sustained-release microcapsules containing a biologically active substance from an W/O emulsion comprising an inner aqueous phase containing said biologically active substance and an external oil phase containing a biodegradable polymer, characterized in that microcapsules formed on microencapsulation of said biologically active substance with said biodegradable polymer are heated at a temperature not lower than the glass transition temperature of said biodegradable polymer but not so high as to cause aggregation of the microcapsules. This method enables the production of very useful sustained release microcapsules adapted to release a bologically active substance at a calculated rate over a protracted time period starting immediately following administration without an initial burst within one day following administration.Type: GrantFiled: August 29, 1996Date of Patent: February 10, 1998Assignee: Takeda Chemical Industries, Ltd.Inventors: Shigeru Kamei, Minoru Yamada, Yasuaki Ogawa
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Patent number: 5705174Abstract: The present invention provides a process for the preparation of microcapsule compositions, methods for using those microcapsule compositions, compositions containing those microcapsule compositions and microcapsules prepared by the process of the present invention.Type: GrantFiled: June 7, 1995Date of Patent: January 6, 1998Assignee: American Cyanamid CompanyInventors: Brian Eric Benoff, Robin William Dexter
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Patent number: 5700929Abstract: A coating base for solid enteric pharmaceutical preparations having a dissolution pH ranging from 3.5 to 4.5 essentially consisting of hydroxypropylmethyl cellulose trimellitate obtained by substituting water-soluble hydroxypropylmethyl cellulose having 1.1 to 1.6 methoxy group per glucose ring thereof with 0.2 to 1.0 trimellitate group per glucose ring, or obtained by substituting water-soluble hydroxypropylmethyl cellulose having 1.7 to 2.1 methoxy groups per glucose ring thereof with 0.2 to 0.5 trimellitate group per glucose ring. The coating base can be dissolved at the upper portion of the small intestine without delay and a solid enteric pharmaceutical preparation provided with a coating film of the base can completely release the drug included therein before the preparation passes through the small intestine. Therefore, the base can ensure a high pharmacological action of the drug.Type: GrantFiled: April 29, 1996Date of Patent: December 23, 1997Assignee: Shin-Etsu Chemical Co., Ltd.Inventors: Hiroyasu Kokubo, Katsuyoshi Minemura
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Patent number: 5688528Abstract: The invention relates to an oil-in-water emulsion comprising 0.01-50% by weight of the total preparation, preferably 0.1-10%, of a galactolipid material as an emulsifier. The galactolipid material consists of at least 50% digalactosyldiacylglycerols, the remainder being other polar lipids. The said emulsion is suitable as a carrier for one or more active substances in a pharmaceutical composition, but also in nutritional, cosmetical, food and agricultural products.Type: GrantFiled: July 15, 1996Date of Patent: November 18, 1997Assignee: Scotia LipidTeknik ABInventors: Anders Carlsson, Marina Delogu, Bengt Herslof
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Patent number: 5686385Abstract: The present invention provides microcapsule comprising agricultural active ingredients with improved physical properties, and an agricultural composition comprising said microcapsule. An agricultural microcapsule having a diameter of not more than 50 .mu.m comprises an agricultural active ingredient in a water-soluble coating material. As an agricultural composition comprising said microcapsules, DL dust, solidified emulsifiable concentrate can be provided.According to the present invention, the agricultural active ingredient is stabilized, agricultural dust can be mixed with even incompatible, liquid agricultural active ingredient, and agricultural microcapsule has excellent handling properties.Type: GrantFiled: June 5, 1995Date of Patent: November 11, 1997Assignee: Takeda Chemical Industries, Ltd.Inventors: Kanji Akashi, Chikara Tanabayashi, Kazutaka Kitagawa
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Patent number: 5679377Abstract: Biodegradable, protein microspheres for in vivo release of a biologically active agent, as well as agricultural and environmental applications. The microspheres can be administered orally, intravenously, or subcutaneously for subsequent release. By selecting particular size ranges and the specific protein used to form the microsphere, it is possible to target the microspheres to a cell types such as macrophages, or to effect localized absorption of the microspheres to regions such as the mucosal membranes of the mouth, gastrointestinal tract, or urogenital areas. Larger forms of the microspheres can also be made using standard techniques of the desirable degradation properties.Type: GrantFiled: June 17, 1994Date of Patent: October 21, 1997Assignee: Alkermes Controlled Therapeutics, Inc.Inventors: Howard Bernstein, Eric Morrel, Edith Mathiowitz, Kirsten Schwaller, Thomas R. Beck
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Patent number: 5672659Abstract: A composition including a polyester containing one or more free COOH groups ionically conjugated with a bioactive polypeptide comprising at least one effective ionogenic amine, wherein the polyester contains a member selected from the group of L-lactic acid, D-lactic acid, DL-lactic acid, .epsilon.-caprolactone, p-dioxanone, .epsilon.-caprolic acid, alkylene oxalate, cycloalkylene oxalate, alkylene succinate, .beta.-hydroxybutyrate, substituted or unsubstituted trimethylene carbonate, 1,5-dioxopan-2-one, 1,4-dioxepan-2-one, glycolide, glycolic acid, L-lactide, D-lactide, DL-lactide, meso-lactide, and any optically active isomers, racemates or copolymers thereof, and at least 50%, by weight, of the polypeptide present in the composition is ionically conjugated to said polyester.Type: GrantFiled: June 29, 1995Date of Patent: September 30, 1997Assignee: Kinerton LimitedInventors: Shalaby W. Shalaby, Steven A. Jackson, Jacques-Pierre Moreau
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Patent number: 5668184Abstract: A method of repelling soil borne pests, nematodes, insects and insect larvae includes applying a solution of naphthalene or precipitated flocculent naphthalene into or upon the soil where the naphthalene volatilizes and repels nematodes and soil pathogens. In another embodiment of the invention, micron size particles of naphthalene are encapsulated in a polymer which is injected into or applied to the surface of the soil. In a further embodiment of the invention, micron-sized particles of naphthalene are attached to a carrier strip which is applied to the surface of the soil as a mulch, applied below the surface of the soil, or attached to trees or plants for repelling pests.Type: GrantFiled: September 6, 1996Date of Patent: September 16, 1997Inventor: A. H. J. Rajamannan
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Patent number: 5652220Abstract: The present invention relates to a microcapsule containing TRH, its analog or a salt thereof and a method of producing the same which attains the release of the active ingredient stably for a prolonged period of time with high rates of incorporation of the active ingredient thereinto and with little possibility of excessive initial release or burst.Type: GrantFiled: April 4, 1995Date of Patent: July 29, 1997Assignee: Takeda Chemical Industries, Ltd.Inventors: Toshiro Heya, Hiroaki Okada, Yasuaki Ogawa
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Patent number: 5651990Abstract: A novel microparticle preparation comprising microparticles of a polymer which contain a drug and are coated with a film of an agent for preventing aggregation of the microparticles is disclosed. The preparation is produced by spraying a solution of a polymer containing a drug and an aqueous solution of an agent for preventing aggregation of the microparticles separately from different nozzles and contacting them with each other in a spray dryer.Type: GrantFiled: February 13, 1995Date of Patent: July 29, 1997Assignee: Takeda Chemical Industries, Ltd.Inventors: Shigeyuki Takada, Yoshiaki Uda, Yasuaki Ogawa
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Patent number: 5651976Abstract: The present invention is a composition for, and a method of, delivering an active agent at a controlled rate. The composition of the invention is a hollow ceramic or inorganic microtubule, where the active agent is contained within the lumen of the microtubules. Typically, the agent is adsorbed onto an inner surface of the microtubule. The method of the invention is disposing this novel composition in a use environment. In a preferred embodiment of the invention, a microtubule is a tubule having an inner diameter of less than 0.2 .mu.m, and microtubules are tubules having an average inner diameter less than 0.2 .mu.m. In a preferred embodiment, the hollow ceramic or inorganic microtubule is a mineral microtubule, such as halloysite, cylindrite, boulangerite, or imogolite. In a more preferred embodiment of the invention, the mineral microtubule has a biodegradable polymeric carrier disposed in its lumen. In a preferred embodiment of the invention, the inner diameter of the microtubules varies from about 0.20 .Type: GrantFiled: July 31, 1995Date of Patent: July 29, 1997Assignee: The United States of America as represented by the Secretary of the NavyInventors: Ronald R. Price, Bruce P. Gaber
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Patent number: 5650102Abstract: In the process for the preparation of microcapsule dispersions by an interface polyaddition process in which an oil-in-water emulsion is prepared from an oily phase, which comprises the substance to be encapsulated and a lipophilic substance capable of polyaddition, and on aqueous phase, and the reaction partner required for the polyaddition is then added to the aqueous phase, capsules with smaller particle sizes are obtained, with a saving in emulsifying energy, if an oil-soluble emulsifier is added to the oily phase before the emulsification.Type: GrantFiled: October 6, 1995Date of Patent: July 22, 1997Assignee: Bayer AktiengesellschaftInventors: Manfred Hagedorn, Peter-Roger Nyssen, Jurgen Weisser
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Patent number: 5648099Abstract: Oxalate-degrading enzymes and bacteria were encapsulated for both enteric and intraperitoneal administration. We have shown that via alginate microencapsulation of Oxalobacter formigenes, enzymatic activity was retained for several months. A new process was developed which strengthened the alginate microcapsules and their tolerance to citrate treatment. Much smaller (30-50 .mu.m) alginate microcapsules were made for injection as means of implantation. For oral administration, multi-encapsulated microspheres of cellulose acetate phthalate in poly-2-vinylpyridine (pKa=3.5) were prepared to protect the enzymes from gastric juices.Type: GrantFiled: February 3, 1994Date of Patent: July 15, 1997Assignee: University of FloridaInventors: Chris Batich, Farid Vaghefi
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Patent number: 5639710Abstract: Microspheres containing an agriculturally active material are produced by mixing a liquid phase containing the agriculturally active material and optionally an emulsifying agent and an aqueous phase containing polyvinyl alcohol and adding a material selected from clays, silicas, starch, and starch derivatives, followed by spray drying.Type: GrantFiled: July 6, 1994Date of Patent: June 17, 1997Assignee: Zeneca LimitedInventors: Ray Jia Lo, Ernesto Noe Villafranca
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Patent number: 5631021Abstract: A microcapsule produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing said water-soluble drug and a drug retaining substance therefor and an oil layer containing a polymer substance, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centiposes and finally subjecting the resulting emulsion to in water drying gives prolonged release of water-soluble drug.Type: GrantFiled: February 20, 1996Date of Patent: May 20, 1997Assignee: Takeda Chemical Industries, Ltd.Inventors: Hiroaki Okada, Yasuaki Ogawa, Takatsuka Yashiki
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Patent number: 5631020Abstract: A microcapsule produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing said water-soluble drug and a drug retaining substance therefor and an oil layer containing a polymer substance, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centiposes and finally subjecting the resulting emulsion to in water drying gives prolonged release of water-soluble drug.Type: GrantFiled: June 6, 1995Date of Patent: May 20, 1997Assignee: Takeda Chemical Industries, Ltd.Inventors: Hiroaki Okada, Yasuaki Ogawa, Takatsuka Yashiki
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Patent number: 5624669Abstract: Hemostatic procedures for sealing punctures and incisions in blood vessels and internal organs involve applying to a puncture or incision surface a biocompatible adhesive composition.Type: GrantFiled: June 7, 1995Date of Patent: April 29, 1997Assignee: Tri-Point Medical CorporationInventors: Jeffrey C. Leung, Jeffrey G. Clark
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Patent number: 5622656Abstract: The invention relates to microcapsules with a mixed wall of crosslinked atelocollagen and polyholosides, for example glycosaminoglycans, and to processes for the manufacture of the said microcapsules.According to the invention, the microcapsules comprise a mixed wall of crosslinked atelocollagen and polyholosides, for example glycosaminoglycans, the proportion of polyholosides, for example glycosaminoglycans, relative to the atelocollagen preferably being between 18 and 50% by weight. These microcapsules can be manufactured either by a process involving interfacial crosslinking or by the extrusion of a laminar flow which is broken up by vibrations into individual droplets, which fall into a crosslinking bath.These microcapsules are biocompatible by virtue of the presence of atelocollagen, which has most of the advantageous properties of collagen, namely a very low antigenicity and a perfect biodegradability.Type: GrantFiled: October 25, 1994Date of Patent: April 22, 1997Assignee: Societe Anonyme: BioeticaInventors: Alain Huc, Marie-Christine Levy, Chantal Buffevant, Marie-Christine Andry
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Patent number: 5622723Abstract: An improvement in the process of coacervation of chlorpheniramine maleate is provided whereby a predetermined amount of chlorpheniramine maleate charged to the process is maintained in the microcapsules by pre-saturating the coacervation medium with chlorpheniramine maleate.Type: GrantFiled: February 3, 1995Date of Patent: April 22, 1997Assignee: Eurand America, IncorporatedInventors: Marie J. Bettman, Sambasiva R. Ghanta
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Patent number: 5620883Abstract: A biocompatible microcapsule containing living cells encapsulated in a membrane is disclosed. The membrane is a complex formed by the cohesion of two polymer layers. An inner layer comprises a substrate biopolymer and an outer layer comprises a synthetic polyelectrolyte having an electrolytic charge opposite that of the substrate biopolymer. Droplets of a solution of substrate biopolymer containing a suspension of living cells can be added to a solution comprising the synthetic polyelectrolyte to form the encapsulates. The membrane is formed by the cohesion of the oppositely-charge polymer layers to form a complex of substrate biopolymer and synthetic polyelectrolyte. Preferably, the inner layer contains a cationic biopolymer, such as collagen modified to have a pKI of 9, or an anionic biopolymer such as esterified or modified hyaluronic acid.Type: GrantFiled: April 1, 1994Date of Patent: April 15, 1997Assignee: The Johns Hopkins UniversityInventors: Wen Shao, Kam W. Leong
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Patent number: 5620699Abstract: Nonaqueous pharmaceutical compositions for use in aqueous physiological systems are disclosed comprising drug delivery vehicles suspended in nonaqueous perfluorocarbon or fluorinated silicone liquid carriers. The suspended drug delivery vehicles may be water labile or water stable and incorporate therapeutic or diagnostic compounds which remain stable and pharmaceutically effective for extended periods. The pharmaceutical compositions have improved bioavailability, are capable of low dose volume delivery, and do not leach the incorporated therapeutic or diagnostic compounds into the liquid carriers making them well suited for multi-dose packaging and administration.Type: GrantFiled: November 13, 1995Date of Patent: April 15, 1997Assignee: Allergan, Inc.Inventor: David L. Meadows
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Patent number: 5609886Abstract: Microspheres which are a matrix of a biocompatible and biodegradable polymer which is soluble in an organic solvent which is immiscible in water, within which a water-soluble substance is uniformly distributed, and wherein the residual level of toxic solvent in the microspheres is lower than 1.5% by weight, progressively and continuously releases the substance over a period of at least 8 days when the microspheres are placed in an aqueous physiological environment, with a reduced or substantially absent first phase of accelerated release. A process for producing such microspheres is provided.Type: GrantFiled: July 26, 1995Date of Patent: March 11, 1997Assignee: Teva Pharmaceutical Industries Ltd.Inventors: Henri Wantier, Fabienne Mathieu, Marc Baudrihaye, Dominique Delacroix
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Patent number: 5603960Abstract: The present invention describes a method for producing microparticles useful in the formulation of pharmaceutical compositions. The present invention further describes a method of immunizing a mammal against diseases comprising administering to a mammal an effective amount of antigen containing microparticles. In particular, the present invention describes a method of potentiating an immune response in a mammal comprising administering an effective amount of a pharmaceutical composition to a mammal. The present invention further describes a vaccine comprising a pharmaceutical composition containing said microparticles. An antigen delivery system comprising microparticles containing entrapped antigens is further described by the present invention. A pharmaceutical composition comprising microparticles and a pharmaceutical carrier is also provided.Type: GrantFiled: June 2, 1995Date of Patent: February 18, 1997Inventors: Derek T. O'Hagan, John P. McGee, Stanley S. Davis
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Patent number: 5597564Abstract: A microgranular preparation having a core of biologically active material that is encapsulated by a water soluble film that is covered by an enteric coating of either an alkali soluble, acid insoluble polymer or a high molecular weight polymer whose structure is substituted with or contains windows of fatty acids or other material capable of being solubilized by intestinal juices. Useful for protecting pH sensitive and other biologically active materials from inactivation or contact with the stomach or rumen, and releasing the same in active form in the intestinal tract, particularly the duodenum.Type: GrantFiled: July 26, 1994Date of Patent: January 28, 1997Assignee: Enzacor Properties LimitedInventor: Thomas K. S. Ying
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Patent number: 5593690Abstract: There is provided a matrix preparation produced by dispersing a pharmaceutically active ingredient into a matrix which is solid at ambient temperature and comprised of a fatty acid ester of a polyglycerol. The preparation has stable release-controlling ability, can be processed to fine granules, granules, capsules, tablets etc., and contributes to reduce the administration times of the active ingredient and side effects of the ingredient.Type: GrantFiled: February 14, 1995Date of Patent: January 14, 1997Assignee: Takeda Chemical Industries, Ltd.Inventors: Yohko Akiyama, Hidetoshi Horibe, Minoru Yoshioka
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Patent number: 5589194Abstract: Microcapsules are prepared by dispersing or dissolving an active component or components in a solid matrix-forming material that has been thermally softened to form an encapsulation composition. The encapsulation composition is injected as an intact stream into a quenching liquid to provide solid microcapsules.Type: GrantFiled: September 20, 1993Date of Patent: December 31, 1996Assignee: Minnesota Mining and Manufacturing CompanyInventors: Alexander C. Tsuei, Lorenz Kogl, III, Daniel B. Pendergrass, Jr.
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Patent number: 5582834Abstract: A biocompatible monomer composition contains (A) at least one monomer of the formula:CHR.dbd.CXYwherein X and Y are each strong electron withdrawing groups, and R is H or, provided that X and Y are both cyano groups, a C.sub.1 -C.sub.4 alkyl group; and (B) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger compound. The monomer is preferably an alpha-cyanoacrylate. The formaldehyde scavenger compound may be in microencapsulated or non-microencapsulated form. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g.Type: GrantFiled: June 5, 1995Date of Patent: December 10, 1996Assignee: Tri-Point Medical, CorporationInventors: Jeffrey C. Leung, Jeffrey G. Clark
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Patent number: 5578325Abstract: Injectable particles are provided that are not rapidly cleared from the blood stream by the macrophages of the reticuloendothelial system, and that can be modified as necessary to achieve variable release rates or to target specific cells or organs as desired. The injectable particles can include magnetic particles or radiopaque materials for diagnostic imaging, biologically active molecules to be delivered to a site, or compounds for targeting the particles. Biodistribution experiments indicate that the injectable particles have a prolonged half-life in the blood compared to particles not containing poly(alkylene glycol) moieties on the surface.Type: GrantFiled: June 24, 1994Date of Patent: November 26, 1996Assignee: Massachusetts Institute of TechnologyInventors: Abraham J. Domb, Ruxandra Gref, Yoshiharu Minamitake, Maria T. Peracchia, Robert S. Langer
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Patent number: 5578580Abstract: A veterinary composition in form of sustained release microcapsules containing erythromycin thiocyanate as active ingredient is disclosed. In the use, said composition is mixed with standard feedstuff in a ratio of 100/200 g per 100 kg (quintal) feedstuff. A process for preparing said composition is also disclosed.Type: GrantFiled: November 20, 1995Date of Patent: November 26, 1996Assignee: Ascor Chimici S.r.l.Inventor: Graziano Sassi
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Patent number: 5575987Abstract: A method of producing sustained-release microcapsules containing a biologically active substance from an W/O emulsion comprising an inner aqueous phase containing said biologically active substance and an external oil phase containing a biodegradable polymer, characterized in that microcapsules formed on microencapsulation of said biologically active substance with said biodegradable polymer are heated at a temperature not lower than the glass transition temperature of said biodegradable polymer but not so high as to cause aggregation of the microcapsules. This method enables the production of very useful sustained release microcapsules adapted to release a bologically active substance at a calculated rate over a protracted time period starting immediately following administration without an initial burst within one day following administration.Type: GrantFiled: November 27, 1995Date of Patent: November 19, 1996Assignee: Takeda Chemical Industries, Ltd.Inventors: Shigeru Kamei, Minoru Yamada, Yasuaki Ogawa
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Patent number: 5576008Abstract: This invention relates to a novel method for preparing pesticide microcapsules in which the release rate and the release period of the pesticide are controlled. A process has been discovered for encapsulating a trace amount of pesticide with a urea-formaldehyde resin, mechanically stirring the resin in the presence of vegetable oil and the pesticide and reacting the mixture under suitable conditions to form a desired pesticide microcapsule.Type: GrantFiled: June 21, 1994Date of Patent: November 19, 1996Assignee: Industrial Technology Research InstituteInventors: Chien-Chun Yang, I-Horng Pan
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Patent number: 5575997Abstract: A biocompatible monomer composition contains (A) at least one monomer of the formula:CHR.dbd.CXYwherein X and Y are each strong electron withdrawing groups, and R is H or, provided that X and Y are both cyano groups, a C.sub.1 -C.sub.4 alkyl group; and (B) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger compound. The monomer is preferably an alpha-cyanoacrylate. The formaldehyde scavenger compound may be in microencapsulated or non-microencapsulated form. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g.Type: GrantFiled: June 5, 1995Date of Patent: November 19, 1996Assignee: Tri-Point Medical CorporationInventors: Jeffrey C. Leung, Jeffrey G. Clark