With Treatment Subsequent To Solid Wall Formation (e.g., Coating, Hardening, Etc.) Patents (Class 264/4.3)
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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: 6319517Abstract: The present invention to relates to a pharmaceutical preparation comprising lyophilized liposomes encapsulating a biologically-active principle which is highly insoluble in water and stable over time.Type: GrantFiled: November 3, 1999Date of Patent: November 20, 2001Assignee: Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A.Inventors: Giovanni Cavallo, Leonardo Marchitto
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Patent number: 6316422Abstract: Novel amidinium derivatives of formula (I), wherein R1 is a cholesterol derivative or an alkylamino-NR′R″ grouping, and each of R2 and R3 is independently a hydrogen atom or a grouping of formula (II), wherein each of R4 and R5 is independently a hydrogen atom or a grouping of formula (III), are disclosed. The corresponding pharmaceutical compositions, which are particularly useful in gene therapy for transferring therapeutic genes into cells, are also disclosed.Type: GrantFiled: November 6, 2000Date of Patent: November 13, 2001Assignee: Centre National de la Recherche ScientifiqueInventors: Jean-Marie Lehn, Pierre Lehn, Jean-Pierre Vigneron
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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
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Patent number: 6306432Abstract: Disclosed are multivesicular liposomes (MVLs) containing IGF-I with substantially full bioavailability, wherein the loading of the IGF-I into the liposomes is modulated by adjusting the osmolarity of the aqueous component into which the agents are dissolved prior to encapsulation. In the making of MVLs, the process involves dissolving the IGF-I, an osmolarity excipient, and a pH modifying agent sufficient to solubilize the IGF-I in a first aqueous component used during manufacture of the MVLs. To increase the loading of the IGF-I, the osmolarity of the aqueous component used during manufacture of the MVLs is reduced, whereas the osmolarity of the aqueous component is increased to obtain the low load formulations. The rate of release of the active agent into the surrounding environment in which the liposomes are introduced can be simultaneously controlled by incorporating into the lipid component used in the formulation at least one long chain amphipathic lipid.Type: GrantFiled: September 8, 1997Date of Patent: October 23, 2001Assignees: Chiron Corporation, SkyePharma Inc.Inventors: Bret Shirley, Maninder Hora, Qiang Ye, Nandini Katre, John Asherman
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Patent number: 6303149Abstract: The present invention relates to a novel process for preparing sol-gel microcapsules loaded with up to 95% (w/w) functional molecules or substances and to the products obtained by said process. Said process is conducted in two steps: (a) creating an oil-in-water emulsion by emulsification of a water insoluble solution comprising the sol-gel precursors and the molecules to be loaded, in an aqueous solution under appropriate shear forces; (b) mixing and stirring said emulsion with an aqueous solution at a suitably selected pH to obtain loaded sol-gel microcapsules in suspension. The microcapsules so obtained can further be subjected to cycles of isolation and rinsing. Incorporation of the final product, either in the form of a suspension or a powder, in cosmetic formulations affords a transparent cream when applying to skin and has a smooth and pleasant contact.Type: GrantFiled: August 11, 1999Date of Patent: October 16, 2001Assignee: Sol-Gel Technologies, Ltd.Inventors: Shlomo Magdassi, David Avnir, Alon Seri-Levy, Noa Lapidot, Claudio Rottman, Yoram Sorek, Orit Gans
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Patent number: 6291013Abstract: 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, a second solvent that is totally or partially immiscible with the first solvent, and sufficient first solvent to saturate the continuous phase; 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 continuous phase 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: May 3, 1999Date of Patent: September 18, 2001Assignee: Southern BioSystems, Inc.Inventors: John W. Gibson, Richard J. Holl, Arthur J. Tipton
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Patent number: 6287593Abstract: A pharmaceutical composition comprising a lipid complex or a liposome of a phospholipid and a water-insoluble platinum dicarboxylate and method for the preparation of such compositions are described.Type: GrantFiled: July 21, 1999Date of Patent: September 11, 2001Assignee: Pharmacia & UpjohnInventor: Mathew Cherian
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Patent number: 6284163Abstract: Inorganic-organic hybrid mixture sol-gel encapsulated lipid vesicles which are composed of silyl lipids or a mixture of silyl lipids and phospholipids are provided. The present invention also provides encapsulated Langmuir Blogget (LB) membranes and biological macromolecules. The sol-gel encapsulated lipid vesicles, LB membranes and proteins possess a higher stability than conventional vesicles. Inorganic-organic hybrid mixture sol-gels are provided as novel sol-gel materials possessing desirable mechanical and physicochemical properties. Also provided are methods of preparing encapsulated lipid vesicles, LB membranes and proteins. Methods of performing renal dialysis using compositions of the invention are also provided.Type: GrantFiled: January 24, 1997Date of Patent: September 4, 2001Assignee: California Institute of TechnologyInventors: Michael H. B. Stowell, Guangyang Wang, Sunney I. Chan
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Patent number: 6264965Abstract: A creamy composition in the form of an oil-in-water emulsion comprising an oily phase dispersed in an aqueous phase, characterized in that it contains at least one anionic emulsifier which is liquid at room temperature, and at least 5% by weight of one or more waxes relative to the total weight of the composition, and in that the oily phase is in the form of a soft paste at room temperature. The anionic emulsifier is preferably a surfactant containing a phosphate group, such as octyldecyl phosphate. The present invention also relates to the uses of the said composition in cosmetics and dermatology, in particular for caring for, treating and/or making up the skin and/or mucous membranes, and more particularly for treating wrinkles and/or fine lines of the skin and/or for treating dry skin. The invention also relates to a process for preparing this composition, characterized in that at least one step of the process is carried out using a mixer-extruder.Type: GrantFiled: December 1, 1999Date of Patent: July 24, 2001Assignee: L'OrealInventors: Veronique Roulier, Pascal Simon
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Patent number: 6261483Abstract: Microcapsules are prepared by polycondensation of a melamine/formaldehyde resin mixture in water, in which essentially water-insoluble material forming the capsule core is dispersed, in the presence of an anionic protective colloid, by a process wherein the melamine/formaldehyde resin mixture is composed of: a) an aqueous solution of a condensate of a1) 1 mol of melamine, a2) from 2 to 5 mol of formaldehyde and a3) from 0 to 0.5 mol of a melamine derivative which can undergo an addition or condensation reaction with formaldehyde and a4) from 1 to 5 mol of a C1-C3-alkanol and b) from 0.01 to 1 mol of a water-soluble primary, secondary or tertiary amine or ammonia.Type: GrantFiled: August 4, 1999Date of Patent: July 17, 2001Assignee: BASF AktiengesellschaftInventors: Gabriele Frank, Ralf Biastoch, Matthias Kummer
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Patent number: 6251314Abstract: The present invention relates to a process for the preparation of microencapsulated polymers having a high surface smoothness, a soluble fraction of less than 6%, and a swelling index of between 1.3 and 9 by polymerizing a microencapsulated monomer mixture suspended in an aqueous phase containing at least one hydroxyaromatic compound as polymerization inhibitor, wherein the microencapsulated monomer mixture contains (a) 34 to 99.7% by weight of a monomer having one polymerizable C═C double bond, (b) 0.1 to 15% by weight of a crosslinking agent having at least 2 polymerizable C═C double bonds, (c) 0.2 to 1.0% by weight of at least one aliphatic peroxyester as polymerization initiator, and (d) 0 to 50% by weight of additives, the percentages being based on the sum of the components (a) to (c).Type: GrantFiled: June 4, 1999Date of Patent: June 26, 2001Assignee: Bayer AktiengesellschaftInventors: Olaf Halle, Werner Strüver, David Bryan Harrison, Wolfgang Podszun
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Patent number: 6241999Abstract: The efficiency of encapsulating a drug into a liposomal formulation is increased by use of a lipid having a carbon chain containing from about 13 to about 28 carbons during preparation of the liposomes. Preferably the liposomes are multivesicular liposomes.Type: GrantFiled: December 6, 1999Date of Patent: June 5, 2001Assignee: SkyePharma, Inc.Inventors: Qiang Ye, Mantripragada Bhima Sankaram
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Patent number: 6228291Abstract: The present invention relates to a process for preparing the controlled-release chitosan microcapsule, more specifically to a process for preparing the sustained-release chitosan microcapsule capable of releasing at an appropriate rate for a long time, which is characterized by: a) Biodegradable chitosan polymer is used for the capsule material; b) The capsule is kept stable during the release time by the rapid and effective crosslinking reaction between the chitosan polymer and the double crosslinking agent on the surface of tiny particles formed by a new emulsion interface reaction method using a double crosslinking agent of sulfuric acid and glutaraldehyde; and c) The microcapsule which is smaller than several &mgr;m s can be easily formed and the capsule is kept stable for a long release time because an insoluble polymer film whose source material is biodegradable is formed after the release.Type: GrantFiled: June 29, 1999Date of Patent: May 8, 2001Assignee: Korea Research Institute of Chemical CompanyInventors: Jung-min Lee, Choong Kyun Yeom, Chul Ung Kim, Beom Sik Kim, Kwang Joo Kim, Sang Bong Oh
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Patent number: 6224794Abstract: A process for forming microspheres that includes passing a first composition containing polymer and solvent through an orifice and directly into a second composition containing water and a microsphere-stabilizing agent, under at least one of conditions (a) and (b), wherein (a) the first composition flows through a first conduit along a first path and exits the first conduit at the orifice, the second composition flows through a second conduit along a second path in an upstream to downstream direction, the first conduit is connected to the second conduit and terminates at the orifice, the first and second paths being orientated at an angle &thgr; relative to each other, wherein 0°<&thgr;<180°; (b) the first composition being at a first temperature and including a solvent having a boiling point, the second composition being at a second temperature, the boiling point of the solvent being less than the second temperature; and forming a composition including water and microspheres, the microspheres bType: GrantFiled: May 5, 1999Date of Patent: May 1, 2001Assignee: Angiotech Pharmaceuticals, Inc.Inventors: Brian G. Amsden, Richard T. Liggins
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Patent number: 6224795Abstract: A process for the preparation of microcapsules by the condensation of melamine-formaldehyde resins and/or the methyl ethers thereof in water, in which the substantially water-insoluble material forming the core of the capsule is dispersed, in the presence of an anionic protective colloid at pH's of from 3 to 6.5 by the formation of the microcapsules at temperatures of from 20° to 50° C. followed by curing of the shell of the capsules at from >50° to 100° C., in which, prior to curing, from 10 to 200 wt % of urea, whose amino groups are optionally linked to an ethylene or propylene bridge, based on the melamine-formaldehyde resin are added, the microcapsules produced by this process and also the use thereof in a pressure-sensitive recording system.Type: GrantFiled: July 26, 1999Date of Patent: May 1, 2001Assignee: BASF AktiengesellschaftInventors: Gabriele Frank, Ralf Biastoch
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Patent number: 6221387Abstract: Microspheres comprising a gelified polar core which is optionally surrounded by concentric and alternating superimposed n lipidic bilayers or n aqueous liquid layers and n gelified polar layers, n being an integer. The microspheres of the invention are obtainable by delipidation of liposomes designated as liposomes having a gelified polar core, of the type comprising at least one outer lipidic bilayer and at least one inner polar aqueous phase containing a gelified substance.Type: GrantFiled: April 28, 1999Date of Patent: April 24, 2001Assignee: LipogelInventors: Jacques Hauton, Jean-Pierre Salles
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Patent number: 6221385Abstract: A process for the preparation of freeze dried liposome encapsulated amphiphilic drug compositions, which process comprises preparing a liposomal suspension of multilamellar vesicles (MLVs) which encapsulate an amphiphilic drug compsition, adding sorbitol to the liposomal suspension and lyophilisation of the suspension.Type: GrantFiled: February 2, 1999Date of Patent: April 24, 2001Assignee: Vrije Universiteit BrusselInventors: Frederic Camu, Robert Brasseur, Franz Legros, Sandra Carlino
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Patent number: 6217886Abstract: Provided are methods for preparing improved biologically active micelle and crystalline products comprising a biologically active amphipathic compound in association with a micelle or crystalline product. Methods for producing the micelle or crystalline products as well as methods of using the micelle or crystalline products in therapeutic, diagnostic, and cosmetic, applications are also provided.Type: GrantFiled: January 27, 1999Date of Patent: April 17, 2001Assignee: The Board of Trustees of the University of IllinoisInventors: Hayat Önyüksel, Israel Rubinstein
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Patent number: 6217899Abstract: A process for the preparation of liposomes is described. The process includes the steps of formation of a lipid film on a ceramic filter, preferably an asymmetric ceramic filter, followed by hydration of the lipid film obtained. The liposomes thus formed are recovered. Multilamellar liposomes prepared by the process are also described.Type: GrantFiled: October 29, 1998Date of Patent: April 17, 2001Assignee: Hassan BenameurInventors: Hassan Benameur, Andre Moes
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Patent number: 6210611Abstract: A method for producing a gas microbubble comprises subjecting the gas microbubble to isothermal conditions or cooling conditions such that the lipid-containing shell cools at a rate ranging from about 100° C./min. to about 103° C./min., and wherein said subjecting step transforms the lipid-containing shell from a liquid state to a solid state.Type: GrantFiled: November 30, 1999Date of Patent: April 3, 2001Assignee: Duke UniversityInventors: David Needham, Dennis Heejong Kim
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Patent number: 6207186Abstract: The invention provides novel compositions involving lamellar gels and methods for making them. These compositions and methods of the invention are significant improvements in the field of gels, macromolecular targeting and macromolecular delivery to various biological systems.Type: GrantFiled: February 13, 1998Date of Patent: March 27, 2001Assignee: The Regents of the University of CaliforniaInventors: Cyrus R. Safinya, Heidi E. Warriner, Stefan H. J. Idziak
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Patent number: 6203816Abstract: The present disclosure relates to novel liposome compositions in which tissue factor is incorporated and methods for their preparation. The composition of the phospholipids in the liposomes has been adjusted to allow maximum coagulant activity and sensitivity to extrinsic coagulation factors of the incorporated tissue factor.Type: GrantFiled: April 24, 1995Date of Patent: March 20, 2001Assignee: Corvas International, Inc.Inventor: Scott M. Brown
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Patent number: 6197349Abstract: Particles comprising (a) a supercooled melt of a poorly water-soluble substance and (b) a stabilizing agent, which have a mean particle size of between 30 and 500 nm, and disperse compositions containing them, as administration forms and delivery systems for drugs, vaccines and other biologically active agents such as herbicides, pesticides, insecticides, fungicides, fertilizers, vitamins, nutrition additives and cosmetics.Type: GrantFiled: November 6, 1997Date of Patent: March 6, 2001Assignee: Knoll AktiengesellschaftInventors: Kirsten Westesen, Britta Siekmann
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Patent number: 6197229Abstract: A method for formulation of high supercoiled DNA content microspheres is described herein. A primary emulsion is formed which optionally contains a DNA nicking inhibitor in addition to DNA with or without buffer. The temperature of the primary emulsion is lowered below the freezing point of the aqueous inner phase which provides increased encapsulation efficiency by decreasing the rate of diffusion of DNA out of the aqueous phase. Thereafter, the primary emulsion is transferred to a water-based surfactant solution and subjected to homogenization to form a secondary microsphere emulsion. The organic phase is removed and the microspheres hardened which are then isolated, frozen and lyophilized.Type: GrantFiled: December 10, 1998Date of Patent: March 6, 2001Assignee: Massachusetts Institute of TechnologyInventors: Shuicho Ando, David Putnam, Robert S. Langer
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Patent number: 6193998Abstract: The efficiency of encapsulating a drug into a liposomal formulation is increased by use of a lipid having a carbon chain containing from about 13 to about 28 carbons during preparation of the liposomes. Preferably the liposomes are multivesicular liposomes.Type: GrantFiled: November 1, 1999Date of Patent: February 27, 2001Assignee: SkyePharma Inc.Inventors: Qiang Ye, Mantripragada Bhima Sankaram
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Patent number: 6183774Abstract: The present invention provides for vitamin A derivative selected from the group consisting of retinol, retinyl ester and any combination thereof incorporated into liposomes formed with alkylammonium fatty acid salts, and methods for manufacturing same. The liposomes of the invention may deliver vitamin A derivative materials at the occurrence of a preset triggering condition. Preferred liposomes of the invention are cationic liposomes. The preferred liposomes of the invention are formed with alkylammonium fatty acid salts, e.g., trialkylammonium fatty acid salts of long chain amides. The encapsulated vitamin A derivative is thus stabilized by the liposomes. The present invention thus also provides a method of stabilizing vitamin A derivative be encapsulation in such liposomes. The liposomes of the invention are used to provide topical skin treatment formulations useful in the treatment of skin.Type: GrantFiled: August 17, 1999Date of Patent: February 6, 2001Assignee: Collaborative Laboratories, Inc.Inventors: Duncan T. Aust, Michael A. Ross, James M. Wilmott, James A. Hayward
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Patent number: 6180136Abstract: The present invention relates to pharmaceutical compositions for the sustained release of pharmacologically active compounds and methods of their manufacture and use. Sustained release times of 10-12 days have been achieved with the present invention. The present invention provides microcrystal compositions. The microcrystals comprise pharmacologically active compounds and are contained within a phospholipid layer which contains a unique combination of phospholipids. The present invention may be applied to a wide range of pharmaceutical compositions which may be rendered suitable for injection. The microcrystals are of varying sizes. At least 50 percent of the microcrystals are from 0.5 &mgr;m to about 3.0 &mgr;m in diameter, at least ten percent of the microcrystals are from about 3.0 &mgr;m to about 10 &mgr;m in diameter, and the composition contains microcrystals which are greater than 10 &mgr;m in diameter.Type: GrantFiled: November 10, 1998Date of Patent: January 30, 2001Assignee: Idexx Laboratories, Inc.Inventors: Kenneth A. Larson, William R. Campbell, Douglas I. Hepler
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Patent number: 6171613Abstract: The efficiency of encapsulating a drug into a liposomal formulation is increased by use of a lipid having a carbon chain containing from about 13 to about 28 carbons during preparation of the liposomes. Preferably the liposomes are multivesicular liposomes.Type: GrantFiled: November 1, 1999Date of Patent: January 9, 2001Assignee: SkyePharma Inc.Inventors: Qiang Ye, Mantripragada Bhima Sankaram