Solid-walled Microcapsule Formed By Physically Removing A Constituent (e.g., Evaporation, Extraction, Etc.) Patents (Class 264/4.6)
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Patent number: 6884372Abstract: Method and apparatus for preparing microparticles using liquid-liquid extraction. A first phase and a second phase are combined to form an emulsion. A portion of the second phase is separated from the emulsion (solvent rich), and the solvent is extracted from the separated second phase, which is then returned (solvent poor) to the emulsion. This process of separation of a solvent rich phase, extraction of solvent, and return of a solvent poor phase, is carried out until a selected level of solvent in the emulsion is achieved. Alternatively, the separated solvent rich phase is not returned to the emulsion, but replaced with another solution, such as an aqueous solution, that is free from solvent. The solvent is preferably extracted into an extraction liquid that functions as a “solvent sink” for the solvent.Type: GrantFiled: April 12, 2004Date of Patent: April 26, 2005Assignee: Alkermes Controlled Therapeutics, Inc. IIInventor: J. Michael Ramstack
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Patent number: 6861016Abstract: Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.Type: GrantFiled: November 17, 2003Date of Patent: March 1, 2005Assignee: Alkermes Controlled Therapeutics Inc. IIInventors: Shawn L. Lyons, Steven G. Wright
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Patent number: 6838089Abstract: The present invention concerns polymer particle vaccine delivery systems in which a water insoluble protein antigen, e.g. a lipidated HpaA protein, is incorporated with particles comprising a polymer matrix. The present invention also concerns a method for incorporating such a water insoluble protein antigen with a polymer matrix in order to produce a polymer particle vaccine delivery system. In addition, the invention also provides a vaccine composition comprising the polymer particle delivery system. The vaccine can be used to treat and/or reduce the risk of for example Helicobacter infection.Type: GrantFiled: April 9, 1999Date of Patent: January 4, 2005Assignee: AstraZeneca ABInventors: Hans Carlsson, Anette Larsson, Erik Söderlind
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Patent number: 6838090Abstract: The present invention provides a drug delivery system comprising a water-insoluble drug, a water-miscible organic solvent for the water-insoluble drug, a surfactant, and water, as well as a process for preparing the same. This invention further provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and such a drug delivery system. In addition, the present invention provides a method of delivering a drug to a host by administering to the host the drug delivery system of the present invention.Type: GrantFiled: June 5, 2003Date of Patent: January 4, 2005Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: S. Esmail Tabibi, Emmanuel I. Ezennia, B. Rao Vishnuvajjala, Shanker Gupta
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Patent number: 6824791Abstract: The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.Type: GrantFiled: January 16, 2004Date of Patent: November 30, 2004Assignee: Brown University Research FoundationInventors: Edith Mathiowitz, Christopher Thanos, Zhi Liu
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Patent number: 6818296Abstract: A microcapsule having a mean diameter of from about 0.1 to about 5 mm, a membrane and a matrix containing at least one active principle wherein the microcapsule is the product of the process comprising the steps of (a) forming an aqueous matrix by heating an aqueous solution comprised of a gel former, a chitosan and active principle; (b) forming a dispersed matrix by adding the aqueous matrix in an oil phase; (c) contacting the dispersed matrix with an aqueous solution of an anionic polymer selected from the group consisting of a salt of alginic acid and an anionic chitosan derivative.Type: GrantFiled: April 4, 2002Date of Patent: November 16, 2004Assignee: Cognis Iberia S.L.Inventors: Josep Garces Garces, Josep-Lluis Viladot Petit
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Patent number: 6815432Abstract: Plasmid-lipid particles which are useful for transfection of cells in vitro or in vivo are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. The particles are typically 65-85 nm, fully encapsulate the plasmid and are serum-stable.Type: GrantFiled: February 24, 2003Date of Patent: November 9, 2004Assignee: Inex Pharmaceuticals Corp.Inventors: Jeffery J. Wheeler, Michael Hope, Pieter R. Cullis, Marcel B. Bally
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Publication number: 20040201117Abstract: A particle coated with a nonlamellar material such as a nonlamellar crystalline material, a nonlamellar amorphous material, or a nonlamellar semi-crystalline material includes an internal matrix core having at least one a nanostructured liquid phase, or at least on nanostructured liquid crystalline phase or a combination of the two is used for the delivery of active agents such as pharmaceuticals, nutrients, pesticides, etc.Type: ApplicationFiled: July 23, 2003Publication date: October 14, 2004Inventor: David Anderson
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Publication number: 20040108609Abstract: Copolymers of lactide and glycolide with high glycolide content. The average glycolate block length is less then about 3, which allows the copolymer to be soluble in slightly polar solvents such as methylene chloride.Type: ApplicationFiled: December 1, 2003Publication date: June 10, 2004Applicant: Alkermes Controlled Therapeutics Inc. IIInventor: Chiem V. Pham
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Patent number: 6746635Abstract: The invention involves methods and products related to the micronization of hydrophobic drugs. A method of micronizing hydrophobic drugs using a set of solutions including an aqueous solution is provided. The invention also relates to products of micronized hydrophobic drugs and related methods of use.Type: GrantFiled: August 8, 2002Date of Patent: June 8, 2004Assignee: Brown University Research FoundationInventors: Edith Mathiowitz, Christopher Thanos, Zhi Liu
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Patent number: 6743438Abstract: Optical lenses and methods of preparing the same, in which an active material encapsulated in resin capsules is impregnated in said lens, adjacent an optical surface thereof. The active material may be a coloring material for producing a printed color pattern in the iris or other areas of the lens, or it may be a therapeutic agent.Type: GrantFiled: November 9, 2001Date of Patent: June 1, 2004Assignee: PBH, Inc.Inventors: Ashok R. Thakrar, Bradley K. Overmyer, William E. Meyers
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Patent number: 6719932Abstract: Disclosed are a plurality of particles having a narrow particle size distribution, a processes for forming the same, and films containing the same. The plurality of particles, includes one or more discrete polymer shells, wherein at least one of the polymer shells is crosslinked with at least one monomer containing two or more double bonds polymerizable by free radical means; and a core material encased in the polymer shells, wherein the plurality of particles have a polydispersity of from 1.3 to 1.0.Type: GrantFiled: September 24, 2002Date of Patent: April 13, 2004Assignee: Shipley Company, L.L.C.Inventors: Richard Roy Clikeman, Morris Christopher Wills, Katerina Elizabeth Dukes
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Patent number: 6713090Abstract: Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.Type: GrantFiled: January 31, 2003Date of Patent: March 30, 2004Assignee: Alkermas Controlled Therapeutics Inc. IIInventors: Shawn L. Lyons, Steven G. Wright
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Patent number: 6706288Abstract: A process for producing parenterally administrable microparticles, in which an at least 20% by weight 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, and the gelled starch particles are dried. A release-controlling shell is optionally also applied to the particles. Microparticles which essentially consist of said starch, have an amino acid content of less than 50 &mgr;g and have no covalent chemical cross-linking.Type: GrantFiled: October 5, 2001Date of Patent: March 16, 2004Assignee: Jagotec AGInventors: Nils Ove Gustavsson, Monica Jönsson, Timo Laakso, Mats Reslow
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Patent number: 6682758Abstract: The present invention provides a drug delivery system comprising a water-insoluble drug, a water-miscible organic solvent for the water-insoluble drug, a surfactant, and water, as well as a process for preparing the same. This invention further provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and such a drug delivery system. In addition, the present invention provides a method of delivering a drug to a host by administering to the host the drug delivery system of the present invention.Type: GrantFiled: June 21, 2001Date of Patent: January 27, 2004Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: S. Esmail Tabibi, Emmanuel I. Ezennia, B. Rao Vishnuvajjala, Shanker Gupta
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Publication number: 20030185896Abstract: Embolic polymer particles are described.Type: ApplicationFiled: August 9, 2002Publication date: October 2, 2003Inventors: Marcia Buiser, Marc Bellisario, David Knapp, Stephan Mangin
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Patent number: 6616949Abstract: A process for producing microparticles containing biologically active substance, in which process an aqueous solution of the said substance is prepared, this solution is mixed with an aqueous solution of PEG such that the substance is concentrated and/or solidified, the substance is optionally washed, the substance is mixed with an organic polymer solution, the composition obtained is mixed, after the admixture of said polymer solution, with an aqueous polymer solution, thereby forming an emulsion of droplets of first mentioned polymer as the internal phase, said droplets are solidified into microparticles, the microparticles are dried and a release-controlling shell is optionally applied to these.Type: GrantFiled: October 5, 2001Date of Patent: September 9, 2003Assignee: Jagotec AGInventors: Monica Jönsson, Timo Laakso, Mats Reslow
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Patent number: 6616948Abstract: Production of purified, parenterally administrable starch by washing starch containing more than 85% amylopectin in order to remove surface-localized proteins, lipids and endotoxins, subjecting the starch to a molecular weight reduction by acid hydrolysis, and optionally removing residual water-soluble proteins. Purified starch and microparticles based on such starch.Type: GrantFiled: October 5, 2001Date of Patent: September 9, 2003Assignee: Jagotec AGInventors: Nils Ove Gustavsson, Monica Jönsson, Per Berdén, Timo Laakso, Mats Reslow
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Publication number: 20030155669Abstract: The present invention discloses apparatus and methods of inducing bubble nucleation to overcome problems commonly associated with preservation by foam formation. Specifically, the invention relates to methods of using bubble nucleation in foam formation to preserve sensitive biological materials. Preferred methods of inducing bubble nucleation include, mixing, chamber rotation, crystals, and ultrasound.Type: ApplicationFiled: October 18, 2002Publication date: August 21, 2003Inventors: Victor Bronshtein, Kevin R. Bracken, John G. Campbell
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Patent number: 6607784Abstract: The present invention provides a method for preparing submicron sized particles of an organic compound, the solubility of which is greater in a water-miscible first solvent than in a second solvent which is aqueous, the process including the steps of (i) dissolving the organic compound in the water-miscible first solvent to form a solution, (ii) mixing the solution with the second solvent to define a pre-suspension; and (iii) adding energy to the pre-suspension to form particles having an average effective particle size of 400 nm to 2 microns.Type: GrantFiled: June 5, 2001Date of Patent: August 19, 2003Assignee: Baxter International Inc.Inventors: James E. Kipp, Joseph Chung Tak Wong, Mark J. Doty, Christine L. Rebbeck
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Patent number: 6605298Abstract: The invention provides a composition for delivering at least one biologically active compound to a living organism, said composition comprising at least one micelle-forming membrane lipidType: GrantFiled: September 5, 2000Date of Patent: August 12, 2003Assignee: Phares Pharmaceutical Research N.V.Inventors: Steven Leigh, Mathew L. S. Leigh
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Patent number: 6592990Abstract: A novel adhesive formed in situ in a microcapsule and method for forming such a pressure sensitive or flowable adhesive in situ in a microcapsule is disclosed. The method for forming the novel adhesive comprises providing an aqueous mixture of wall material in water; adding a substantially water insoluble core material, free radical initiator, and a solvent for the pre-polymers to the aqueous mixture. The core material comprises a first addition polymerizable pre-polymer having a Tg of less than about 0° C., a flash point of at least 75° C., and a boiling point of at least 175° C. These are typically selected from acrylate or methacrylate type materials. Optionally included is a second addition polymerizable pre-polymer for providing cross-linking or interaction between polymer chains. High shear agitation is provided to the aqueous mixture to achieve a particle size of about 0.1 to 250 microns.Type: GrantFiled: August 30, 2001Date of Patent: July 15, 2003Assignee: Appleton Papers Inc.Inventor: Todd Arlin Schwantes
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Patent number: 6592844Abstract: A process is described for preparing microspheres, films and coatings from protein or modified protein in which the protein product is stabilized by carrying out the preparation in the presence of an aqueous solution of at least one &agr;-hydroxy acid. The microspheres, films and coatings so produced have improved stability in aqueous solution.Type: GrantFiled: December 27, 1999Date of Patent: July 15, 2003Assignees: Chiron Corporation, University of NottinghamInventors: Allan G. A. Coombes, Wu Lin, Derek T. O'Hagen, Stanley S. Davis
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Patent number: 6569405Abstract: Microcapsules are prepared by a process comprising the steps of (i) spray-drying a solution or dispersion of a wall-forming material in order to obtain intermediate microcapsules and (ii) reducing the water-solubility of at least the outside of the intermediate microcapsules. Suitable wall-forming materials include proteins such as albumin and gelatin. The microcapsules have walls of 40-500 nm thick and are useful in ultrasonic imaging. The control of median size, size distribution and degree of insolubilization and cross-linking of the wall-forming material allows novel microsphere preparations to be produced.Type: GrantFiled: September 28, 1999Date of Patent: May 27, 2003Assignee: Quadrant Healthcare (UK) LimitedInventors: Andrew D. Sutton, Richard A. Johnson, Peter J. Senior, David Heath
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Patent number: 6565777Abstract: Bioactive agent is encapsulated in a polymer microparticle in a (water-in-oil)-in-water emulsion-based method, and using a solvent that comprises ethyl acetate. Also described are microparticles comprising low inherent viscosity (i.v.) PLG, some with i.v. less than 0.5 dl/g, and methods for their preparation. DNA release is modified through use of low i.v. PLG. A particle production method for scale-up uses a blender that avoids excessive shear damage to DNA being encapsulated.Type: GrantFiled: May 29, 2002Date of Patent: May 20, 2003Assignee: Microbiological Research AuthorityInventors: Graham Henry Farrar, Anne Margaret Tinsley-Bown, David Hughes Jones
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Patent number: 6537586Abstract: Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.Type: GrantFiled: April 1, 2002Date of Patent: March 25, 2003Assignee: Alkermes Controlled Therapeutics Inc. IIInventors: Shawn L. Lyons, Steven G. Wright
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Patent number: 6537583Abstract: The invention concerns a method for preparing mineral capsules consisting of aqueous liquid core enclosed in mineral coating, said method consisting in: 1) emulsifying an aqueous fluid in a phase non-miscible with said aqueous fluid so as to disperse it therein in the form of droplets; 2) contacting, in the resulting emulsion, at least a zirconium, silicon, aluminium and/or a transition metal capable of being hydrolysed or subjected to condensation polymerisation in temperature and pH conditions suitable for forming a precipitate consisting of the corresponding oxide or hydroxide; 3) recuperating the resulting mineral capsules and, if required, purifying them.Type: GrantFiled: July 19, 2001Date of Patent: March 25, 2003Assignee: Rhodia ChimieInventors: Dominique Dupuis, Catherine Jourdat
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Patent number: 6534484Abstract: Plasmid-lipid particles which are useful for transfection of cells in vitro or in vivo are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. The particles are typically 65-85 nm, fully encapsulate the plasmid and are serum-stable.Type: GrantFiled: November 8, 1999Date of Patent: March 18, 2003Assignee: Inex Pharmaceuticals Corp.Inventors: Jeffery J. Wheeler, Michael Hope, Pieter R. Cullis, Marcel B. Bally
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Patent number: 6534094Abstract: A process for the manufacturing of microcapsules for sustained release of water soluble peptides, with adjustable release periods of between 1 to 18 weeks. The microcapsule wall are made of a biodegradable polymer. The process is based on the formation of an intermediate complex water/oil/water emulsion. By evaporating the solvent in the emulsion by pressure reduction the microcapsules consolidate, retaining the active peptides in the polymeric matrix. The process produces the complex emulsion in a two mixer, continuous operation. In the first mixer a water/oil emulsion is formed and it is used to form the complex emulsion in the second mixer. By operating in a continuous manner, the process overcome the problems found in existing processes regarding particle size distribution, material losses and process control, among others.Type: GrantFiled: May 3, 2001Date of Patent: March 18, 2003Assignee: Eriochem S.A.Inventors: Nora Moyano, Jose Iturraspe, Jose Lucio Nunez
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Publication number: 20030042638Abstract: 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: ApplicationFiled: August 15, 2002Publication date: March 6, 2003Inventor: Martin L. Kantor
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Patent number: 6528092Abstract: Synthetic membranes, micelles and vesicles are formed in response to the spontaneous orientation of hydrophobic and hydrophilic groups in aqueous media. The oligosaccharide moieties of glycoprotein molecules are oriented toward the aqueous environment. The micelles of the present invention are relatively stable in aqueous environments, and thus are useful for transporting substances that can be dissolved or suspended in lipids for inclusion in the micelles. Lipo-glycoprotein micelles are also useful for protecting substances contained within the hydrophobic compartment from dispersal or degradation until the micelle structure is disrupted.Type: GrantFiled: August 12, 1999Date of Patent: March 4, 2003Inventor: Elaine H. Mullen
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Patent number: 6514523Abstract: This invention relates to a carrier particle having a diameter of from 5 to 20 nm which contains an HDL apolipoprotein, an amphipathic lipid such as a phospholipid, and a drug which is either a hydrophobic drug, amphipathic drug, or a cationic hydrophilic drug. The carrier particle is formed by a process in which the components are co-sonicated in a buffer. The apolipoprotein is preferably apo A-I or apo A-II. The carrier particle is particularly useful for increasing plasma circulation time of a hydrophobic drug relative to conventional hydrophobic drug carrier particles. Thus, drug efficacy is improved and toxicity of the drug to renal and reticuloendothelial tissues is reduced. A composition for drug delivery comprises the carrier particle suspended in a pharmaceutically acceptable medium, and is particularly suited to administration by parenteral infusion, systemic injection, transdermal patch, oral tablet or oral spray.Type: GrantFiled: February 14, 2000Date of Patent: February 4, 2003Assignee: Ottawa Heart Institute Research CorporationInventor: Daniel L. Sparks
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Patent number: 6500461Abstract: This invention provides vehicles capable of delivering high concentrations of poorly hydrophilic/poorly lipophilic compounds to animals, by combining compounds having biocompatible hydrophobic domains with conjugates having both hydrophobic and hydrophilic regions. Such formulations are suitable for a number of uses in animals, particularly the administration thereto of high concentrations of therapeutically useful compound, without an undue level of side effects.Type: GrantFiled: May 19, 1999Date of Patent: December 31, 2002Assignee: The Liposome CompanyInventors: Walter Perkins, Xingong Li, Donald Hirsh, Eric Mayhew, Imran Ahmad, Shaukat Ali, Andrew Janoff
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Patent number: 6471995Abstract: Method and apparatus for preparing microparticles using liquid-liquid extraction. A first phase and a second phase are combined to form an emulsion. A portion of the second phase is separated from the emulsion (solvent rich), and the solvent is extracted from the separated second phase, which is then returned (solvent poor) to the emulsion. This process of separation of a solvent rich phase, extraction of solvent, and return of a solvent poor phase, is carried out until a selected level of solvent in the emulsion is achieved. Alternatively, the separated solvent rich phase is not returned to the emulsion, but replaced with another solution, such as an aqueous solution, that is free from solvent. The solvent is preferably extracted into an extraction liquid that functions as a “solvent sink” for the solvent.Type: GrantFiled: September 27, 2000Date of Patent: October 29, 2002Assignee: Alkermes Controlled Therapeutics, Inc. IIInventor: J. Michael Ramstack
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Patent number: 6461545Abstract: 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: January 6, 2000Date of Patent: October 8, 2002Assignee: Emisphere Technologies, Inc.Inventor: Martin L. Kantor
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Patent number: 6451338Abstract: A method is provided for the formation of liposomes of 0.1 &mgr;m to 50 &mgr;m in diameter having unilamella or multilamella structure and containing water insoluble or undissolved particulate materials comprising (a) forming liposomes and removing substantially all of any organic solvent used in their preparation, (b) freeze drying the liposomes so formed and then (c) rehydrating them in intimate admixture with the particulate material. Preferred encapsulated materials are particulate materials, most preferably microorganisms, plant or animal cells or water insoluble structures having organic solvent labile biochemical or immunological activity, but any water insoluble particulate may be encapsulated using the method. For example catalysts or drugs that are sparingly soluble may also be so incorporated such that slow release into the a patients body may be provided while release of detergents included in the many liposome preparation protocols may be avoided.Type: GrantFiled: September 27, 2001Date of Patent: September 17, 2002Assignee: The Secretary of State for Defence in Her Britannic Majest's Government of the United Kingdom of Great Britain and Northern IrelandInventors: Gregory Gregoriadis, Sophia George Antimisiaris, Ishan Gursel
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Patent number: 6447800Abstract: This invention provides methods of loading preformed liposomes by transmembrane permeation induced by alcohols. Solutes loaded into liposomes by this ethanol mediated process include both small nonpolar molecules and larger species, such as proteins and carbohydrates.Type: GrantFiled: January 18, 1996Date of Patent: September 10, 2002Assignee: The University of British ColumbiaInventor: Michael J. Hope
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Patent number: 6440493Abstract: Processes for making microparticles, preferably containing an active agent, are provided. In a preferred embodiment, the process involves preparing (1) a dispersed phase containing an agent in a solution of polymer and a first solvent; (2) a continuous phase containing a surfactant, and a second solvent that is totally or partially immiscible with the first solvent; and (3) an extraction phase that is a nonsolvent for the polymer, a solvent for the continuous phase components, and a solvent for the first solvent, wherein the first solvent has solubility in the extraction phase of between about 0.1% and 25% by weight. Then, the dispersed phase and the continuous phase are mixed to form an emulsion, and the emulsion is then briefly mixed with a suitable quantity of extraction phase to induce skin formation at the interface of the dispersed and continuous phases. Remaining solvent is removed by an evaporation process step.Type: GrantFiled: November 29, 2000Date of Patent: August 27, 2002Assignee: Southern Biosystems, Inc.Inventors: John W. Gibson, Richard J. Holl, Arthur J. Tipton
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Patent number: 6428815Abstract: Submicron particles of a biologically active agent are prepared by atomizing using multifluid atomization a dispersed system comprising at least one biologically active agent and at least one solvent to produce droplets, freezing the droplets to produce frozen droplets, lyophilizing the frozen droplets to obtain microstructures capable of being further fragmented into submicron particles by techniques such as probe sonication. The submicron particles can be incorporated into sustained release compositions having a reduced initial release of biologically active agent. The sustained release compositions can be administered to a human or animal.Type: GrantFiled: July 3, 2001Date of Patent: August 6, 2002Assignee: Alkermes Controlled Therapeutics, Inc.Inventors: Henry R. Costantino, Warren E. Jaworowicz, Mark A. Tracy, Christopher P. Beganski
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Publication number: 20020086971Abstract: Copolymers of lactide and glycolide with high glycolide content. The average glycolate block length is less then about 3, which allows the copolymer to be soluble in slightly polar solvents such as methylene chloride.Type: ApplicationFiled: February 1, 2002Publication date: July 4, 2002Inventor: Chiem V. Pham
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Patent number: 6395304Abstract: Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.Type: GrantFiled: April 10, 2001Date of Patent: May 28, 2002Assignee: Alkermes Controlled Therapeutics Inc. IIInventors: Shawn L. Lyons, Steven G. Wright
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Patent number: 6391452Abstract: The present invention relates to pharmaceutical compositions for delivery of drugs intended to reside in the nose, compositions for nasal administration of drugs, e.g., antiviral agents, and particularly antiviral agents comprising the human major rhinovirus receptor, also known as intercellular adhesion molecule-1 (ICAM-1); to methods of making said nasal drug compositions, and to an improved process for the removal of residual solvent from pharmaceutical matrices.Type: GrantFiled: July 17, 1998Date of Patent: May 21, 2002Assignee: Bayer CorporationInventors: Kris P. Antonsen, Rajiv Nayar, Wei Wang, Margaret Caudle, Michael A. Shearer, Neville M. Concessio
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Patent number: 6372260Abstract: A process for the incorporation of an active substance in a carrier system by forming an emulsion of the components and precipitating the system by the use of fluid gas technique.Type: GrantFiled: April 30, 1999Date of Patent: April 16, 2002Assignee: AstraZeneca ABInventors: Marie-Louise Andersson, Catherine Boissier, Anne Mari Juppo, Anette Larsson
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Patent number: 6355267Abstract: The present invention relates to a method of producing liposomes useful for encapsulating and delivering a wide variety of biologically active materials. The invention provides liposomes and a production method which is simple, feasible and inexpensive for the large-scale commercial manufacturing of liposomes and encapsulated materials. The method involves the formation of a liposome dispersion in the absence of an organic solvent or detergent, one or several cycles of freezing and thawing the liposomes, and dehydration of the liposome dispersion to form a lipid powder. When desired, the lipid powder is hydrated in the presence of the biologically active material whereby the material is encapsulated in reconstituted liposomes. The method can also include combining the liposome dispersion with a bulking agent prior to the dehydration and formation of the lipid powder. The addition of the bulking agent facilitates the handling of the lipid powder as well as its rapid dispersal upon hydration.Type: GrantFiled: June 3, 1997Date of Patent: March 12, 2002Assignee: Amgen Inc.Inventor: David Collins
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Patent number: 6352716Abstract: Methods and compositions are described for the preparation of bioactive agents entrapped in lipid vesicles the bilayers of which comprise a salt form of an organic acid derivative of a sterol, such as the tris-salt form of a sterol hemisuccinate, and to bompositions comprising a mixtue of tris(hydroxymethyl)aminomethane salt of cholesteryl hemisuccinate with either an antifungal compound or a peptide. These compositions have various applications in vivo.Type: GrantFiled: August 18, 1993Date of Patent: March 5, 2002Assignee: The Liposome Company Inc.Inventors: Andrew S. Janoff, Mircea C. Popescu, Alan L. Weiner, Lois E. Bolcsak, Paul A. Tremblay, Christine E. Swenson
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Patent number: 6348214Abstract: Provided are methods for preparing improved biologically active liposome products comprising a biologically active amphipathic compound in association with a liposome. Methods for producing the liposome products as well as methods of using the liposome products in therapeutic and diagnostic techniques are also provided.Type: GrantFiled: August 1, 2000Date of Patent: February 19, 2002Assignee: The Board of Trustees of the IllinoisInventors: Hayat Onyuksel, Israel Rubinstein
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Patent number: 6331314Abstract: In the procedure for the production of a formulation of parenterally administrable pharmaceutical preparations, a liposome dispersion is used as a carrier for a pharmaceutical active compound. For the preparation of the liposome dispersion, an aqueous predispersion of one or more amphiphilic substances is fed to a high-pressure homogenizer in which the predispersion is pumped under a pressure from 600 bar to 900 bar through a homogenizer nozzle (2) having a diameter of 0.1 to 0.5 mm. The homogenizer nozzle has an inlet channel (14, 16) and an outlet channel (15, 18) and consists of a hard ceramic plate (11), in which the bore (13) is present, pressed into a steel body (12, 19). The inlet channel (14, 16) and the outlet channel (15, 18) are likewise incorporated into the steel body (12, 19).Type: GrantFiled: May 12, 1998Date of Patent: December 18, 2001Assignee: Bayer AktiengesellschaftInventors: Bernd Klinksiek, Said Mahiout, Ricarda-Christine Nothelle, Hans-Jürgen Hamann, Jürgen Sdebik
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Patent number: 6331317Abstract: Apparatus and method for preparing microparticles. An emulsion is formed by combining two phases in a static mixing assembly. The static mixing assembly preferably includes a preblending static mixer and a manifold. The emulsion flows out of the static mixing assembly into a quench liquid whereby droplets of the emulsion form microparticles. The residence time of the emulsion in the static mixing assembly is controlled to obtain a predetermined particle size distribution of the resulting microparticles.Type: GrantFiled: November 12, 1999Date of Patent: December 18, 2001Assignee: Alkermes Controlled Therapeutics II Inc.Inventors: Shawn L. Lyons, Steven G. Wright
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Patent number: 6322809Abstract: A method is provided for the formation of liposomes of 0.1 &mgr;m to 50 &mgr;m in diameter having unilamella or multilamella structure and containing water insoluble or undissolved particulate materials comprising (a) forming liposomes and removing substantially all of any organic solvent used in their preparation, (b) freeze drying the liposomes so formed and then (c) rehydrating them in intimate admixture with the particulate material. Preferred encapsulated materials are particulate materials, most preferably microorganisms, plant or animals cells or water insoluble structures having organic solvent labile biochemical or immunological activity, but any water insoluble particulate may be encapsulated using the method. For example, catalysts or drugs that are sparingly soluble may also be so incorporated such that slow release into the patient's body may be provided while release of detergents included in the many lipoome preparation protocols may be avoided.Type: GrantFiled: September 20, 1996Date of Patent: November 27, 2001Assignee: The Secretary of State for Defence in Her Brittanic Majesty's Government of the United Kingdom of Great Britain and Northern IrelandInventors: Gregory Gregoriadis, Sophia George Antimisiaris, Ihsan Gursel
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Patent number: 6309569Abstract: Bioactive agent is encapsulated in a polymer microparticle in a (water-in-oil)-in-water emulsion-based method, and using a solvent that comprises ethyl acetate. Also described are microparticles comprising low inherent viscosity (i.v.) PLG, some with i.v. less than 0.5dl/g, and methods for their preparation. DNA release is modified through use of low i.v. PLG. A particle production method for scale-up uses a blender that avoids excessive shear damage to DNA being encapsulated.Type: GrantFiled: May 13, 1999Date of Patent: October 30, 2001Assignee: Microbiological Research AuthorityInventors: Graham Henry Farrar, Anne Margaret Tinsley-Bown, David Hugh Jones