Enzyme Or Microbial Cell Is Entrapped Within The Carrier (e.g., Gel, Hollow Fibre) Patents (Class 435/182)
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Patent number: 5618736Abstract: A process using hydrothermally synthesized porous kaolinite as a carrier for use in a bioreactor. A carrier-biocatalyst composite body for use in a bioreactor, includes the synthesized kaolinite as a carrier and a biocatalyst fixed onto the synthesized kaoline. A bioreactor system includes a bioreactor vessel, and such a carrier-biocatalyst composite body placed in the bioreactor vessel.Type: GrantFiled: June 20, 1994Date of Patent: April 8, 1997Assignee: NGK Insulators, Ltd.Inventor: Kisato Tone
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Patent number: 5601835Abstract: Disclosed is a polymeric drug delivery system for delivery of any substance to the central nervous system. The delivery system is preferably implanted in the central nervous system for delivery of the drug directly to the central nervous system. These implantable devices can be used, for example, to achieve continuous delivery of dopamine, which cannot pass the blood brain barrier, directly into the brain for an extended time period. The implantable devices display controlled, "zero-order" release kinetics, a life time of a minimum of several weeks or months even when the devices contain water soluble, low molecular weight compounds, biocompatibility, and relative non-invasiveness. The polymeric devices are applicable in the treatment of a variety of central nervous system disorders including Parkinson's disease, Alzheimer's dementia, Huntington's disease, epilepsy, trauma, stroke, depression and other types of neurological and psychiatric illnesses.Type: GrantFiled: January 12, 1994Date of Patent: February 11, 1997Assignee: Massachusetts Institute of TechnologyInventors: Bernhard A. Sabel, Andrew Freese, William M. Saltzman, Matthew J. During
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Patent number: 5595909Abstract: A filter device containing cell masses and single cells is described. The device contains porous hollow fibers and hepatocytes entrapped within a contracted gel matrix.Type: GrantFiled: March 31, 1995Date of Patent: January 21, 1997Assignee: Regents of the University of MinnesotaInventors: Wei-Shou Hu, Frank B. Cerra
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Patent number: 5589370Abstract: The present invention relates to an improved curing or hardening process for the continuous production of capsules containing a sensitive material. The process allows capsules to be formed continuously without aggregating. The process is also a contained system so that exposure to possibly harmful aerosols is avoided.Type: GrantFiled: August 1, 1995Date of Patent: December 31, 1996Assignee: Lever Brothers Company, Division of Conopco, Inc.Inventors: Florencio Ratuiste, Robert Ahart, David J. Lang, Liang S. Tsaur
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Patent number: 5585183Abstract: A method for preparing liquid-core microcapsules for cell cultures, using a hardening solution containing CaCl.sub.2 and polyethyleneimine to harden gel-core beads before coating them with polylysine solution.Type: GrantFiled: April 13, 1994Date of Patent: December 17, 1996Assignee: National Science CouncilInventor: I-Ming Chu
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Patent number: 5578314Abstract: A method for multiple layer coating of biological tissue and cells for transplantation. The cell or tissue transplants are coated with multiple coatings of purified alginate. The method includes applying the first coat of sodium alginate gelled with divalent cations followed by optional treatment with strontium, barium or other divalent cation, resuspending the single coated droplets in sodium alginate and forming the halo layer around the first coating via exchange or diffusion of divalent cations from the single coating to the surrounding soluble alginate, removing the excess coating and gelling the remaining thin layer of soluble alginate with divalent cations. The coated transplants have distinct structure where biological tissue or cell core is covered with the first alginate coat, which is surrounded by an intermediate halo layer which is covered by the outer coating.Type: GrantFiled: January 24, 1994Date of Patent: November 26, 1996Assignee: The Regents of the University of CaliforniaInventors: Kent C. Cochrum, Randel E. Dorian, Susan A. Jemtrud
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Patent number: 5578442Abstract: In accordance with the present invention, there are provided methods to render cells non-adhesive and/or non-immunogenic with respect to macromolecules typically encountered in culture media or in physiological media. The invention method comprises contacting cells with an effective amount of a composition comprising a polycationic species having water-soluble polymer chains grafted thereon.Type: GrantFiled: March 23, 1992Date of Patent: November 26, 1996Assignee: VivoRx, Inc.Inventors: Neil P. Desai, Patrick Soon-Shiong, Paul A. Sandford, Roswitha E. Heintz
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Patent number: 5573934Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.Type: GrantFiled: March 1, 1993Date of Patent: November 12, 1996Assignee: Board of Regents, The University of Texas SystemInventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet S. Sawhney, Neil P. Desai, Jennifer L. Hill-West, Syed F. A. Hossainy
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Patent number: 5567608Abstract: Biocatalysts such as cells and enzymes are immobilized in a polymer gel by forming a mixture containing a biocatalyst, an N,N-dialkylacrylamide monomer, a cationic acrylamide monomer and a water-soluble cross-linking monomer, and copolymerizing the monomers to produce a polymer gel entrapping the biocatalyst. Preferably, the N, N-dialkylacrylamide is N,N-dimethylacrylamide or N,N-diethylacrylamide in an amount of about 70 to about 99.8% by weight, the cationic acrylamide monomer is N,N-dimethylaminopropylacrylamide, N,N-dimethylaminopropylmethacrylamide, N,N-diethylaminopropylmethacrylamide, N,N-diethylaminopropylacrylamide and quaternary compounds thereof in a amount of about 0.1 to about 10% by weight and the cross-linking monomer is N,N'-methylenebisacrylamide, N,N'-methylenebismethacrylamide, N,N'-(1,2-dihydroxyethlene)bisacrylamide, 1,3-diacrylamide methyl-2-imidazolidone or diacrylamide methylene urea in an amount of about 0.1 to about 20% by weight.Type: GrantFiled: January 9, 1995Date of Patent: October 22, 1996Assignee: Nitto Chemical Industry Co., Ltd.Inventors: Toshiaki Doi, Hiroyasu Bamba, Kouzou Murao
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Patent number: 5563056Abstract: A chemical specie is immobilized in a three dimensional, crosslinked matrix by bringing together in covalent bonding proximity a desired chemical specie and a polymeric coupling compound such as a photoderivatized polymer having at least two latent photochemical reactive groups per molecule, each latent reactive group being capable when activated of covalently bonding to another coupling compound molecule or to the chemical specie. The chemical specie may be a protein, carbohydrate, nucleic acid or lipid, and desirably is free of latent reactive groups that are activated upon activation of the latent reactive groups of the coupling compound. The latent reactive groups are simultaneously activated to cause formation via covalent bonding of a three-dimensional molecular network in which molecules of the chemical specie are covalently bonded to molecules of the coupling compound, and molecules of the coupling compound are covalently bonded to each other.Type: GrantFiled: February 27, 1995Date of Patent: October 8, 1996Assignee: BSI CorporationInventors: Dale G. Swan, Mark W. Josephson, Melvin J. Swanson
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Patent number: 5560909Abstract: The invention concerns certain insecticidal compositions of ingestible insecticides selected from the group consisting of DNA viruses, RNA viruses and bacteria of the order Bacillus such as, for example, Bacillus thuringiensis var. israelensis entrapped by a suitable charged polymer. The invention also concerns a process for the preparation of and the use of such insecticidal compositions.Type: GrantFiled: July 26, 1991Date of Patent: October 1, 1996Assignee: DowElancoInventors: Lisa J. Rheaume, Julia A. Gegner, James J. Jakubowski, Daniel H. Haigh, James Peters
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Patent number: 5545423Abstract: The present invention is directed to a macrocapsule for encapsulating microcapsules containing biologically active material, such as living cells or free living cells, to make the system more biocompatible by decreasing the surface area and surface roughness of microencapsulated biological materials; increasing mechanical stability of microencapsulated biological materials; enhancing cytoprotectivity by increasing diffusion distance of encapsulated biological material from cytotoxins secreted in vivo; providing retrievability of microencapsulated material; and providing a system of sustained release of the cellular products. The method for producing such a macrocapsule containing the microcapsules is also disclosed.Type: GrantFiled: March 6, 1995Date of Patent: August 13, 1996Assignee: VivoRx, Inc.Inventors: Patrick Soon-Shiong, Neil P. Desai, Roswitha E. Heintz
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Patent number: 5543309Abstract: A carrier is prepared containing bacteria and/or enzymes for degrading sewage sludge. The carrier can be in the form of a gel containing coloring matter and optionally a deodorant, or in the form of a core for a roll of toilet tissue or a roll of towels. In a preferred embodiment, the carrier is in the form of a tube that is used as a core for a roll of toilet tissue. The tube is formed from at least two layers made from cellulose bonded together with a water soluble bonding agent. Enzymes and/or bacteria can be in a slurry of cellulose pulp used to make the core, in the bonding agent, or in a coating or strip on an inside and/or outside layer. The tube contains a plurality of sets of circumferential perforations that enable, after removing toilet tissue, readily breaking the tube into a plurality of small pieces that can be flushed down a toilet bowl into a sewage system where the pieces disintegrate and release the enzymes and/or bacteria.Type: GrantFiled: November 28, 1994Date of Patent: August 6, 1996Inventor: Ernie Pischel
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Patent number: 5531997Abstract: Cell or tissue transplant coated with an insoluble immunological barrier comprising a noncytotoxic first layer of a gellable organic polymer and a cationic polymer and a second noncytotoxic, water-soluble, semi-permeable layer chemically bonded to the first layer. A method for coating the cell or tissue with the insoluble immunologically inert barrier.Type: GrantFiled: June 5, 1995Date of Patent: July 2, 1996Assignee: The Regents of University of CaliforniaInventor: Kent C. Cochrum
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Patent number: 5529914Abstract: This invention provides novel methods for the formation of biocompatible membranes around biological materials using photopolymerization of water soluble molecules. The membranes can be used as a covering to encapsulate biological materials or biomedical devices, as a "glue" to cause more than one biological substance to adhere together, or as carriers for biologically active species. Several methods for forming these membranes are provided. Each of these methods utilizes a polymerization system containing water-soluble macromers, species which are at once polymers and macromolecules capable of further polymerization. The macromers are polymerized using a photoinitiator (such as a dye), optionally a cocatalyst, optionally an accelerator, and radiation in the form of visible or long wavelength UV light. The reaction occurs either by suspension polymerization or by interfacial polymerization.Type: GrantFiled: October 7, 1992Date of Patent: June 25, 1996Assignee: The Board of Regents the Univeristy of Texas SystemInventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet S. Sawhney, Neil P. Desai, Syed F. A. Hossainy
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Patent number: 5529913Abstract: Contaminating protein is removed from a water soluble gum such as alginate by dialyzing a solution of the gum against a solution of a disulphide bond reducing agent. Purifying the gum by removing antigenic protein improves biocompatability of the gum for making biocompatible capsules containing cells such as mammalian cells. The reducing agent is preferably dithiothreitol, dithioerythritol or 2-mercaptoethanol. Dialyzing is preferably carried out for more than 1 hour and more preferably twice, each time for 2 hours. Cells are encapsulated by forming a suspension of cells in an aqueous solution of the gum, forming droplets from the suspension, gelling the droplets with a multivalent cation, contacting the gelled droplets with a polymer containing cationic groups, such as poly-1-lysine chloride, that cross-link with anionic groups of the gum to form a semi-permeable membrane around the droplets, and coating the membrane with a layer of the dialyzed gum.Type: GrantFiled: June 22, 1994Date of Patent: June 25, 1996Assignee: University of LeicesterInventors: Heather A. Clayton, Roger F. L. James, Nicholas J. M. London
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Patent number: 5521089Abstract: Microorganism cells such as Saccharomyces or Candida yeast cells are treated with an alkaline aqueous solution with heating and stirring or with a cell wall dissolving enzyme such as glucanase or mannase to obtain cells that function as microcapsules by rapidly taking up a large amount of hydrophobic liquid. Treatment with an alkaline aqueous solution is preferably carried out at a pH of at least 8 for at least 1 hour at a temperature of 20.degree.-100.degree. C. A preferred embodiment of enzyme treatment is with .beta.-1,3-glucanase for about 30 minutes to 5 hours at pH 4-9 at a temperature of 30.degree.-60.degree. C. The treatments dissolve cell walls of the yeast such that the walls still have sufficient strength for enclosing hydrophobic liquids.Type: GrantFiled: January 7, 1994Date of Patent: May 28, 1996Assignees: Mitsubishi Paper Mills Limited, Kirin Brewery Company, LimitedInventors: Mamoru Ishiguro, Yutaka Shimura, Naomu Ishiwaki
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Patent number: 5516648Abstract: Reference microorganisms are sealed into an interior cavity of a microporous membrane (14, 20). In one embodiment, the reference microbes are inoculated on a element (12) which is sealed in a microporous envelope (14) (FIG. 1). In another embodiment, the reference microbes (22) are loaded into an interior bore or cavity of a microporous plastic tube or envelope (20) (FIG. 3). The microporous membrane and the reference microbes, such as spores, are immersed concurrently with items to be microbially decontaminated separately into an anti-microbial fluid. The microporous membrane is constructed of a material which is sufficiently resistant to temperature, water, strong oxidants, and other anti-microbial agents or processes used for microbial decontamination or sterilization that it retains its integrity during the immersion in any common steam, gas, or liquid microbial decontamination or sterilization fluid or system.Type: GrantFiled: August 18, 1994Date of Patent: May 14, 1996Assignee: Steris CorporationInventors: Paul S. Malchesky, Donna M. Richardson
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Patent number: 5514377Abstract: A method for in situ dissolution of an alginate coating from transplants containing biological tissue cores by administering to a transplant's recipient a physiologically acceptable chelating agent in an amount sufficient to dissolve the alginate coating. The method allows in situ removal of the coating and deactivation of the transplant by rejection of its core by the host immune system without the necessity to perform a surgery.Type: GrantFiled: March 8, 1994Date of Patent: May 7, 1996Assignee: The Regents Of The University Of CaliforniaInventors: Kent C. Cochrum, Susan A. Jemtrud
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Patent number: 5510257Abstract: Most of the problems of prior art techniques for growing cells in hollow fiber devices can be avoided by growing the cells in short lengths (e.g., two inches (5.0 cm.) or less) of microporous hollow fibers. The fibers are prepared by chopping commercial lengths of hollow fibers into small pieces, preferably two inches (5 cm.) or smaller. Such chopped hollow fibers or bundles of hollow fibers are then added to a suitable medium for growth of cells and the medium is incubated. Very high cell densities have been observed in the chopped fibers.Type: GrantFiled: October 4, 1989Date of Patent: April 23, 1996Inventors: Kamalesh K. Sirkar, Rajesh K. Shukla
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Patent number: 5494811Abstract: A fluidized bed reactor system which utilizes a fluid phase, a retained fluidized primary particulate phase, and a migratory second particulate phase. The primary particulate phase is a particle such as a gel bead containing an immobilized biocatalyst. The secondary and tertiary particulate phases, continuously introduced and removed simultaneously in the cocurrent and countercurrent mode, act in a role such as a sorbent to continuously remove a product or by-product constituent from the fluid phase. Means for introducing and removing the sorbent phases include feed screw mechanisms and multivane slurry valves.Type: GrantFiled: January 26, 1995Date of Patent: February 27, 1996Assignee: Martin Marietta Energy Systems, Inc.Inventors: Charles D. Scott, Joseph A. Marasco
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Patent number: 5486292Abstract: Highly porous, adsorbent biocatalyst beads of synthetic organic polymer have powdered activated carbon dispersed throughout the polymer and a biocatalyst, such as bacteria, located within macropores of the beads. The beads are used for remediation of contaminated aqueous streams. The biocatalyst can consume adsorbed organic contaminants and convert them into harmless gases, while continuously renewing the adsorptive capacity of the activated carbon.Type: GrantFiled: March 3, 1994Date of Patent: January 23, 1996Assignee: E. I. Du Pont de Nemours and CompanyInventors: Thomas I. Bair, Carl E. Camp
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Patent number: 5484721Abstract: A process and apparatus are provided for making solid particles from an ionically cross-linkable material by cross-linking drops of the material with a cross-linking agent in the form of a falling stream. In one embodiment, a stream of the cross-linking agent flows down the inner walls of an enclosure and drops of the material are directed to the stream of cross-linking agent. In another embodiment, a stream of the cross-linking agent is free-falling by gravity in a cascade without contacting any surface and drops of the material are directed to the stream of cross-linking agent. Solid particles are separated from the cross-linking agent at about the bottom of the enclosure or at about the bottom of the cascade. The drops of cross-linkable material are directed at the stream of cross-linking agent preferably at an angle of incidence of less than 90.degree. such as between 5.degree. and 45.degree. and most preferably between 15.degree. and 30.degree.. Particles having a size of 10 .mu.Type: GrantFiled: April 19, 1993Date of Patent: January 16, 1996Assignee: LVMH RechercheInventors: Patrick Ors, Dominique Hennequin, Alain Meybeck
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Patent number: 5470731Abstract: Transplants are coated with an insoluble immunological barrier membrane. The membrane can comprise a non-cytotoxic first layer of agarose and cationic amino acid polymer and a non-cytotoxic second layer chemically bonded to said first layer, the second layer comprising an anionic amino acid polymer. The molecular weight of the anionic amino acid polymer is preferably in the range of 2000 to 500,000 daltons, and the thickness if the total membrane coating is within the range of 1 and 100 microns. Alternatively, the membrane can comprise a non-cytotoxic first layer of a cationic amino acid polymer. A non-cytotoxic second layer chemically bonded to the first layer comprises agarose and an anionic amino acid polymer. A non-cytotoxic optional third layer chemically bonded to said second layer comprises a cationic amino acid polymer.Type: GrantFiled: June 8, 1994Date of Patent: November 28, 1995Assignee: The Regents of the University of CaliforniaInventor: Kent C. Cochrum
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Patent number: 5462866Abstract: Microspheres of a substantially uniform diameter are produced having a central portion composed of a solution of a polyanion containing a biological material, and an outer permeable membrane enclosing the central portion which is a complex of the polyanion and a polycation. The biological material has a molecular size greater than 150,000 Daltons, and the membrane has a porosity such that the biological material does not permeate the membrane. The biological material may comprise living cells or living tissue. The microspheres are formed by individually enveloping falling droplets of a polyanion solution with a collapsing annular sheet of a polycation solution while the sheet is traveling downwardly at the same velocity as the droplets.Type: GrantFiled: September 23, 1993Date of Patent: October 31, 1995Assignee: Vanderbilt UniversityInventor: Taylor G. Wang
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Patent number: 5462861Abstract: A method for regulating enzyme activity, which entails contacting one or more enzymes with a gas containing one or more noble gases or mixtures thereof. The activity of an enzyme on a substrate can be improved by contacting the enzyme with a noble gas under specific temperatures and pressures. The preferred noble gases are krypton, neon, xenon, argon or mixtures of these gases. The enzymes whose activity can be improved are hydrolases, lyases, isomerases and ligases.Type: GrantFiled: May 17, 1993Date of Patent: October 31, 1995Assignee: American Air Liquide, Chicago Research CenterInventors: Kevin C. Spencer, Pascal Schvester, Christine E. Boisrobert
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Patent number: 5459054Abstract: Cells such as mammalian or genetically modified cells are encapsulated in high-G alginate that provokes reduced immune response during transplantation or implantation. The alginate contains greater than 50% .alpha.-L-guluronic acid and a minimal amount of mannuronic acid. The amount of .alpha.-L-guluronic acid is preferably at least 65% and more preferably at least 85%. Encapsulation is carried out by suspending cells in a solution of the high-G alginate, forming drops of the solution and contacting the drops with calcium ions to gel the alginate and form microcapsules containing the cells. The microcapsules may contain multiple layers with the high-G alginate preferably forming the outermost layer.Type: GrantFiled: July 2, 1993Date of Patent: October 17, 1995Assignee: Neocrin CompanyInventors: Gudmund Skjak-Braek, Olay Smidsrod, Terje Espevik, Marit Otterlei, Patrick Soon-Shiong
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Patent number: 5453270Abstract: There is disclosed a pharmaceutical composition and method for metabolic consumption of calories and weight loss. The pharmaceutical composition is a culture of brown adipose cells, preferably encapsulated in a porous growth matrix, and a semipermeable membrane encapsulating the porous matrix wherein the semipermeable membrane has a molecular weight cutoff of at least 10,000 daltons and, preferably, a lipoprotein lipase embedded therein. Further disclosed is a pharmaceutical composition for metabolizing fatty acids into carbon dioxide, water and heat including a mammalian cell stably transfected with a DNA sequence coding for a mammalian UCP polypeptide, wherein the transfected mammalian cell transcribes and translates UCP polypeptide.Type: GrantFiled: March 2, 1993Date of Patent: September 26, 1995Assignee: Hypermetabolic Therapies, Inc.Inventor: Nathan Bills
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Patent number: 5453368Abstract: A method for encapsulating a biological substance is biocompatible microcapsules is disclosed, said method comprising:a) maintaining a coating-forming liquid film sheet comprising a solution of a soluble organic polymer in an organic solvent,b) causing droplets comprising biological substance is an aqueous medium to pass through said sheet to form microcapsules comprising cores of said droplets coated by said liquid film, andc) permitting said microcapsules to pass through said sheet so that a portion of said polymer precipitates in the presence of water in said droplets while evaporating a portion of said solvent to form a continuous permeable polymer coating of sufficient structural that said microcapsules are self-supporting.Type: GrantFiled: August 27, 1993Date of Patent: September 26, 1995Assignee: Brown University Research FoundationInventors: Patrick A. Tresco, John F. Mills
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Patent number: 5447864Abstract: A method of separating cell nuclei from cells comprises: treating a fluid containing whole cells so as to selectively lyse the cytoplasmic membrane together with a small proportion of the nuclear membranes but leaving a large proportion of the cell nuclei intact; applying the treated fluid to a membrane whereby a mesh of DNA from the lysed nuclei is formed on the surface and captures intact cell nuclei. A device for use in the method is described.Type: GrantFiled: September 14, 1993Date of Patent: September 5, 1995Assignee: Amersham International LimitedInventors: Margaret P. Raybuck, Michael K. Kenrick, David A. Parry, Andrew L. Bertera, John G. Anson, Nicola M. Williamson
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Patent number: 5443975Abstract: Enzymes, cells and/or cellular organelles are bound to an insoluble sintered expanded clay support matrix for catalyzing transformations of agriculture and industrial residues in soil and in other environments. In one embodiment, an enzyme is absorbed by the sintered expanded clay support matrix and a phenolic monomer is polymerized or copolymerized on the support matrix containing the bound enzyme. In another embodiment, an enzyme different from the enzyme absorbed by the support matrix is combined with the phenolic monomer and a copolymer of enzyme and phenolic monomer is formed on the support matrix containing the bound enzyme. The phenolic monomer is preferably catechol, pyrogallic acid and/or resorcinol.Type: GrantFiled: December 10, 1992Date of Patent: August 22, 1995Assignees: Ente Per Le Nuove Technologie, L'Energia E L'Ambiente (ENEA), Consiglio Nazionale Delle RicercheInventors: Stefano Cervelli, Vincenzo Capuano
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Patent number: 5441878Abstract: An apparatus and method for the formation of droplets of uniform size on a laboratory scale are described. A syringe having a plunger and a needle with an orifice at the tip corresponding to a 12-30 gauge needle is inserted into a block member having a cavity such that the needle of the syringe extends through an opening in the bottom of the block member. The block member has a gas inlet into a side of the cavity for flowing of gas pass the orifice of the needle. The block member is mounted in a support housing such that the syringe is in a vertical position. To form droplets, pressure is applied to the plunger, preferably by a piston under gas pressure, to force liquid from the needle tip orifice to form droplets and flowing gas pass the tip to detach droplets of a desired size.Type: GrantFiled: December 8, 1987Date of Patent: August 15, 1995Assignee: Thies Technology, Inc.Inventors: Curt Thies, Andrew Stanisz
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Patent number: 5434069Abstract: The present invention relates to a novel capsule for protecting sensitive ingredients in detergent compositions. The capsule, in addition to a protected sensitive ingredient, contains an oil dispersion containing the active and a polymer shell surrounding the dispersion. The oil is defined by its ability to meet a tripartite definition and the shell is a water soluble or water dispersible polymer as defined.Type: GrantFiled: November 12, 1993Date of Patent: July 18, 1995Assignee: Lever Brothers Company, Division of Conopco, Inc.Inventors: Liang S. Tsaur, Shiji Shen, Michael P. Aronson, David J. Pocalyko
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Patent number: 5429932Abstract: A multilayer analytical element has been prepared for accurate and rapid colorimetric determination of ethanol in aqueous specimens using alcohol dehydogenase and an oxidized nicotinamide coenzyme. The element includes two reagent layers beneath a porous spreading layer. The element also contains niacinamide in one or more layers to reduce the interference from alcohols other than ethanol.Type: GrantFiled: May 24, 1993Date of Patent: July 4, 1995Assignee: Eastman Kodak CompanyInventors: Richard L. Detwiler, Robert J. Ferris
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Patent number: 5429931Abstract: A multilayer analytical element has been prepared for accurate and rapid colorimetric determination of ethanol in aqueous specimens using alcohol dehydrogenase and an oxidized nicotinamide coenzyme. The element includes at least one reagent layer beneath a porous spreading layer. This reagent layer has a crosslinked polymeric binder prepared, in part, with a polymerizable monomer having a halomethylcarbonyl, haloethylcarbonyl, halomethylsulfonyl or haloethylsulfonyl group. Alcohol dehydrogenase is in a layer of the element for reaction with the analyte.Type: GrantFiled: May 24, 1993Date of Patent: July 4, 1995Assignee: Eastman Kodak CompanyInventors: Richard L. Detwiler, Stephen C. Hasselberg, Ignazio S. Ponticello
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Patent number: 5429821Abstract: A transplant comprising a core of a viable, physiologically active cells coated with a non-fibrogenic alkaline earth metal alginate free from fibrogenic amounts of fucose, sulfate, phloroglucinol and protein moieties, having a mannuronate to guluronate molar ratio of from 1.2 to 6. The coating protects the core from host immunological destruction after transplantation. The coating is sufficiently permeable to permit the diffusion of nutrients and cell products through the coating.A process for coating the transplant core comprising coating the core with alginate substantially free from fibrogenic compounds and reacting the alginate coating with alkaline earth metal cations comprising calcium ions or magnesium ions or mixture thereof to form an alkaline earth metal alginate coating.Type: GrantFiled: May 29, 1992Date of Patent: July 4, 1995Assignee: The Regents of the University of CaliforniaInventors: Randel E. Dorian, Kent C. Cochrum, Susan A. Jemtrud
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Patent number: 5427935Abstract: Material such as biological material is encapsulated within a semi-permeable hybrid membrane bead by suspending the material in a medium which comprises an effective amount of a gelling inducer; forming said suspension into a droplet of a size sufficient to envelop said material, suspending a second material in a gelling solution comprising an effective amount of a gel forming polymer which gels upon contact with said gelling inducer forming a discrete bead by contacting the outer surface portion of the droplet with a gelling solution, and allowing the gelling solution to thicken sufficiently for the second material to become entrapped therein.Type: GrantFiled: June 29, 1993Date of Patent: June 27, 1995Assignee: The Regents of the University of MichiganInventors: Henry Y. Wang, Somesh C. Nigam
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Patent number: 5426042Abstract: A BOD analyzer is prepared having a microbe sensor containing an oxygen electrode and a microbe membrane. The microbe membrane is made by immobilizing microorganisms belonging to the genus Klebsiella in the membrane. Specifically, the BOD analyzer has a flow cell equipped with a microbe sensor containing an oxygen electrode and a microbe membrane, and a liquid passage which is connected with an entrance of the flow cell and which is equipped with an outlet. The microbe membrane is made by immobilizing microorganisms belonging to Klebsiella oxytoca 12092 strain in a porous hydrophilic membrane having an average pore size of 0.65-3 .mu.m in diameter by using at least one gelating agent selected from alginic acid or salts thereof, agar, gellan gum, xathane gum, gelatine, carageenan, locust bean gum, methylcellulose, pectin, or pullulan. The BOD analyzer can be used for batch or continuous BOD analysis and enables carrying out BOD analysis in a short period of time.Type: GrantFiled: January 7, 1994Date of Patent: June 20, 1995Assignee: Nakano Vinegar Co., Ltd.Inventors: Shigeru Maeda, Akira Ohki, Takeshi Sato, Naho Kato, Hirofumi Akano, Yoshiya Kawamura, Keizo Hatagaki, Yasushi Takahashi, Mikio Yamada, Hajime Okumura
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Patent number: 5419902Abstract: This invention relates to a method for inactivating pathogens using the peroxidase enzyme. The peroxidase enzyme is reacted with hydrogen peroxide or a source of hydrogen peroxide and an iodide anion to generate reaction products which are separated from the peroxidase enzyme and then used to inactivate pathogenic organisms.Type: GrantFiled: July 16, 1993Date of Patent: May 30, 1995Assignee: Symbollon CorporationInventor: Jack Kessler
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Patent number: 5418154Abstract: Elongated seamless capsules containing biological material are prepared by a method in which a coagulant, which includes a cell suspension or other biologically active factor, and a polymeric casting solution are extruded through a common extrusion port having at least two concentric bores, such that the coagulant is extruded through the inner bore and the polymeric casting solution is extruded through the outer bore. The method involves initiating extrusion of the coagulant subsequent to initiating delivery of the casting solution through the respective bores to form a capsule having a curved and smooth leading edge shape. Delivery of the coagulant is then shut off, and extrusion of the casting solution is terminated either immediately or after some predetermined time.Type: GrantFiled: December 24, 1992Date of Patent: May 23, 1995Assignee: Brown University Research FoundationInventors: Patrick Aebischer, John F. Mills, Lars Wahlberg, Edward J. Doherty, Patrick A. Tresco
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Patent number: 5413924Abstract: A reagent such as an enzyme is entrapped in a material such as wax or a liposome that releases the reagent when heated. In a preferred embodiment, wax beads containing the reagent are prepared by injecting the reagent into beads of molten wax and cooling to solidify the wax. In another embodiment, droplets of a solution of the reagent are dropped through a layer of molten wax to coat the droplets with the wax and the coated droplets are cooled to solidify the wax. The entrapped reagents have application in nucleic acid hybridizations, polymerase chain reactions (PCR), reverse transcriptase reactions (RTR), nucleic acid sequencing, and product generating reactions such as colorimetic, fluorometric and chemiluminescent enzyme labeled immunoassays.Type: GrantFiled: August 27, 1992Date of Patent: May 9, 1995Inventors: Kenneth M. Kosak, Matthew K. Kosak
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Patent number: 5409822Abstract: A fluidized bed reactor system utilizes a fluid phase, a retained fluidized primary particulate phase, and a migratory second particulate phase. The primary particulate phase is a particle such as a gel bead containing an immobilized biocatalyst. The secondary particulate phase, continuously introduced and removed in either cocurrent or countercurrent mode, acts in a secondary role such as a sorbent to continuously remove a product or by-product constituent from the fluid phase. Introduction and removal of the sorbent phase is accomplished through the use of feed screw mechanisms and multivane slurry valves.Type: GrantFiled: June 29, 1993Date of Patent: April 25, 1995Assignee: Martin Marietta Energy Systems, Inc.Inventors: Charles D. Scott, Joseph A. Marasco
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Patent number: 5405764Abstract: Immobilized water-insoluble biocatalysts in particulate form comprise living cells, particularly yeast, dispersed in a cross-linked gelling agent. An enzyme, particularly amyloglucosidase, may be co-immobilized in the particles. These particles are prepared by suspending the living cells in an aqueous solution of a gelling agent, dispersing this suspension in a water immiscible organic liquid to form a suspension in the liquid of aqueous particles comprising the living cells and gelling agent, gelling the gel and cross-linking the gelling agent. It is found that when living cells such as microbial cells and especially yeast are immobilized in this way, that surprisingly, not only is their viability retained, but the ability of yeast cells to produce ethanol under continuous fermentation conditions is significantly improved. Specific strains of Saccharomyces cerevisiae, suitable for immobilization in this way, are described.Type: GrantFiled: April 8, 1994Date of Patent: April 11, 1995Assignee: Gist-Brocades N.V.Inventors: Abraham Harder, Ben R. DeHaan, Johannes B. Van der Plaat, Marsha Cummings
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Patent number: 5403750Abstract: Affinity matrices useful for the chromatography and immobilization of biological materials and the method of preparing and using the same are disclosed. The affinity supports are based on hydrated polyurethane polymers which have been activated to provide a means for covalently attaching a variety of bioaffinity agents. The hydrated polymer matrices are characterized by their biocompatibility and resistance to nonspecific protein adsorption. Preferably, the prepolymers used to prepare the hydrated polymers are isocyanate-capped oxyethylene-based diols or polyols, at least 75% of said diols and polyols having a molecular weight of 7000 to about 30,000.Type: GrantFiled: April 8, 1991Date of Patent: April 4, 1995Assignee: W. R. Grace & Co.-Conn.Inventors: James A. Braatz, Aaron H. Heifetz
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Patent number: 5399665Abstract: Polymers more suitable for use in organ transplantation are formed by coupling biologically active moieties to the free amino groups of polymers formed by incorporation of .alpha. amino acids into polymers formed of alpha hydroxy acids such as lactic acids. In the preferred embodiment, the peptides are coupled to the free amino groups.Type: GrantFiled: November 5, 1992Date of Patent: March 21, 1995Assignees: Massachusetts Institute of Technology, Children's HospitalInventors: Denise Barrera, Robert S. Langer, Peter T. Lansbury, Jr., Joseph P. Vacanti
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Patent number: 5397700Abstract: A method of providing and sustaining a difference in pH of a first reaction of an immobilized enzyme and a second reaction in a bulk liquid surrounding the immobilized enzyme is carried out with a bilayer pellet containing coimmobilized enzymes. The pellet can contain an enzyme that produces a desired product immobilized in an inner core and urease immobilized in an outer layer. The bulk liquid contains urea and a substrate for the enzyme in the core, and has an acidic pH. The urease reacts with urea diffusing into the outer layer from the bulk liquid to produce ammonia. The ammonia consumes hydrogen ions diffusing into the inner core from the acidic bulk liquid. This provides the enzyme in the inner core with a pH higher than the acidic pH of the bulk liquid suitable for the enzyme to react with the substrate as it diffuses into the inner core.Type: GrantFiled: September 23, 1993Date of Patent: March 14, 1995Assignee: University of ToledoInventors: Ronald L. Fournier, Sasidhar Varanasi, James P. Byers
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Patent number: 5389532Abstract: A polysaccharide gel enclosing microorganisms is soaked in a high concentration of hydrophilic substance and the gel is at least partially dehydrated to provide improved viability of the microorganisms after storage and rehydration of the gel. Dehydration may be carried out in a fluidized bed or by lyophilization. The gel may be in the form of beads or fibers having a double layer structure formed by an internal layer or core of gel containing the microorganisms and an external layer or envelope of gel essentially devoid of the microorganisms. The hydrophilic substance can be a low molecular weight polyol such as glycerol or a sugar such as sucrose, and is preferably sucrose in a concentration of at least 500 g/l, more preferably about 1000 g/l. The microorganisms in the gel are preferably yeast and after rehydration the yeast-containing gel is used in the secondary fermentation of wine to produce sparkling wine or champagne.Type: GrantFiled: November 22, 1993Date of Patent: February 14, 1995Assignee: Champagne Moet & ChandonInventors: Charles Divies, Pascal Lenzi, Jacques Beaujeu, Frederic Herault
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Patent number: 5389535Abstract: Methods and systems are disclosed for encapsulating viable cells which produce biologically-active factors. The cells are encapsulated within a semipermeable, polymeric membrane by co-extruding an aqueous cell suspension and a polymeric solution through a common port to form a tubular extrudate having a polymeric outer coating which encapsulates the cell suspension. For example, the cell suspension and the polymeric solution can be extruded through a common extrusion port having at least two concentric bores, such that the cell suspension is extruded through the inner bore and the polymeric solution is extruded through the outer bore. The polymeric solution coagulates to form an outer coating. As the outer coating is formed, the ends of the tubular extrudate can be sealed to form a cell capsule. In one embodiment, the tubular extrudate is sealed at intervals to define separate cell compartments connected by polymeric links.Type: GrantFiled: December 17, 1993Date of Patent: February 14, 1995Assignee: Brown University Research FoundationInventors: Patrick Aebischer, Lars Wahlberg
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Patent number: 5387522Abstract: Biological material is entrapped in a hydrophilic gel by using an apparatus containing a biphasic spray head. In a preferred embodiment, mammalian cells are mixed with a solution of alginate to form a mixture and the mixture is fed to a biphasic spray head where the mixture passes through a nozzle surrounded by an annular passageway through which air is passed. Droplets of the mixture are formed at the tip of the nozzle and air passing through the passageway frees the droplets from the tip and propels them into the atmosphere in the form of fine spherical droplets. The droplets then contact a solution of divalent cation such as calcium chloride which gels the alginate. Preferably, the nozzle has an inner diameter of between about 0.006" and 0.016" and is beveled at an angle between about 15.degree. and 30.degree. to form a conical tip.Type: GrantFiled: July 22, 1991Date of Patent: February 7, 1995Assignee: Schering CorporationInventors: Paul J. Vasington, Maurice M. Lynch, Maureen E. Frye
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Patent number: 5378462Abstract: Pancreatin-containing micropellet cores which can be coated with a gastric juice-resistant film are prepared by extruding a mixture containing pancreatin, polyethylene glycol 4000 and a lower alcohol such as propan-2-ol to produce extrudates which break by themselves into fragments, rounding the fragments with the addition of highly liquid paraffin and drying. Propan-2-ol may be present with the paraffin during rounding. The micropellet cores contain 65-85% pancreatin, and have a bulk density of 0.6 g/ml to 0.85 g/ml, a spherical to ellipsoidal shape with a minor axis in the range of 0.7-1.4 mm and a particle size distribution in which at least 80% of the micropellet cores have a minor axis to major axis ratio in the range from 1:1 to 1:2.Type: GrantFiled: August 19, 1993Date of Patent: January 3, 1995Assignee: Kali-Chemie Pharma GmbHInventors: Bernd Boedecker, Friederike Henninges, Klaus-Juergen Koelln, Guenther Kuhnow, Guenter-Josef Peschke, Manfred Rehburg, Alwin Sobe, Berthold Stemmle