Enzyme Or Microbial Cell Is Entrapped Within The Carrier (e.g., Gel, Hollow Fibre) Patents (Class 435/182)
  • Patent number: 5106633
    Abstract: A food-grade oxygen scavenger for removing oxygen from foods and beverages in containers is prepared by immobilizing dried yeast containing at least 92% dry matter in a solid material such as wax or paraffin. The solid material allows for very slow penetration of water and permits the yeast to contact only water that penetrates therethrough. The immobilized yeast is coated on an inside surface of a container or on a surface of a closure such as a stopper that is on the inside of the container when closed. After adding a food or beverage and closing the container, the immobilized yeast removes oxygen from the container. The closed container and its contents can be pasteurized and the yeast retain sufficient viability to remove oxygen.
    Type: Grant
    Filed: January 10, 1991
    Date of Patent: April 21, 1992
    Assignee: Gist-Brocades NV
    Inventors: Luppo Edens, Farrokh Farin, Antonius F. Ligtvoet, Johannes B. Van Der Plaat
  • Patent number: 5106627
    Abstract: Neurological therapy devices are disclosed for the local and controlled delivery of a neurotransmitter to the brain of a subject suffering from neurotransmitter deficiency or dysfunction. In one embodiment the device includes a biocompatible, implantable, and retrievable polymeric insert including a source of neurotransmitter embedded therein. In another embodiment, the device includes a retrievable source of neurotransmitter including at least one neurotransmitter-secreting cell encapsulated within a semipermeable membrane allowing the diffusion therethrough of the neurotransmitter, and further includes a source of growth factor in close proximity to the neurotransmitter-secreting cells.
    Type: Grant
    Filed: November 14, 1990
    Date of Patent: April 21, 1992
    Assignee: Brown University Research Foundation
    Inventors: Patrick Aebischer, Shelley R. Winn
  • Patent number: 5102799
    Abstract: Immobilized lipase is prepared by forming a mixture of hydrophilized polyolefin fibers, crude porcine pancreas lipase, one or more water soluble dihydric to hexahydric aliphatic alcohols of 2 to 6 carbons and an aqueous buffer solution of pH 5-9 at a temperature of 0.degree. to 40.degree. C., allowing the mixture to stand for 1 minute to 3 days, filtering the mixture and washing the resultant filter cake. The dihydric to hexahydric alcohol may be combined with one or more water soluble monohydric alcohols having 1 to 4 carbon atoms. The immobilized lipase is used for resolving racemates of esters of racemic alcohols in an aqueous medium.
    Type: Grant
    Filed: November 4, 1988
    Date of Patent: April 7, 1992
    Assignee: BASF Aktiengesellschaft
    Inventors: Dieter Urban, Wolfgang Ladner, Axel Paul
  • Patent number: 5102795
    Abstract: A process for obtaining sorbitol and gluconic acid or gluconate from aqueous glucose/fructose mixtures by using Zymomonas mobilis cells which have been permeabilized by treatment with cationic surfactant is disclosed. The permeabilized cells are preferably obtained by treatment with long-chain quaternary alkylammonium salts such as, in particular, CTAB, Dodigen or Bardac. Surfactant concentrations of 0.1 to 0.3% and a treatment time of 1 to 10 minutes at room temperature are expedient. The cell concentrations preferably used for the fermentation are 20 to 80 g/1 dry matter of permeabilized cells.
    Type: Grant
    Filed: October 31, 1990
    Date of Patent: April 7, 1992
    Assignee: Forschungszentrum Juelich GmbH
    Inventors: Bert Rehr, Hermann Sahm
  • Patent number: 5093253
    Abstract: Microbial cells are immobilized by entrapment in gellan gum, also known as deacetylated heteropolysaccharide S-60. Entrapment can be carried out by forming a mixture of a paste of microbial cells and an aqueous solution of gellan gum and adding the mixture drop-wise to an aqueous solution of cations to produce beads of hardened gellan gum entrapping the microbial cells. The microbial cells preferably contain aspartase activity and can be E. coli ATCC 11303, and the cations are preferably magnesium ions. In an alternative embodiment, the mixture of microbial cell paste and aqueous gellan gum solution is admixed with a porous cationic exchange resin which is preferably in magnesium ion form and the microbial cells are entrapped in hardened gellan gum in and on the resin.
    Type: Grant
    Filed: July 2, 1990
    Date of Patent: March 3, 1992
    Assignee: Monsanto Company
    Inventor: Carol L. Nolan
  • Patent number: 5089407
    Abstract: Biological materials such as enzymes, proteins and peptides are encapsulated by forming a mixture of the material and an aqueous non-ionic polymer solution, spraying the mixture into a circulating water-immiscible nonsolvent for the polymer at a temperature sufficient to freeze the beads and drying the frozen beads to remove essentially all unbound water such as to provide a water content of about 1-2 weight percent. Suitable non-ionic polymers are poly(vinyl alcohol), polyvinylpyrollidone, dextran and derivatized cellulose. A densification agent such as alumina may be present in the polymer solution to enhance specific gravity of the beads formed. Encapsulated material such as microbes produced by this process provide useful agricultural agents which can be delivered to the market in a dormant state and suitable for delivery to soil or plant leaves. The beads can be applied dry, via a planting or an insecticide box, or wet via a spray nozzle.
    Type: Grant
    Filed: November 17, 1989
    Date of Patent: February 18, 1992
    Assignee: Monsanto Company
    Inventors: Carol A. Baker, Albert A. Brooks, Robert Z. Greenley, Jay M. Henis
  • Patent number: 5089479
    Abstract: The invention is a carbohydrate receptor for Mycoplasma pneumoniae and Mycoplasma hominus and its use to detect mycoplasma in biological fluids and diseased tissue and cells. The receptor can be included in a composition having a pharmaceutically acceptable carrier. Methods are provided for purifying, detecting, or removing mycoplasma from diseased tissue or fluids. The receptor includes sulfatides, dextran sulfate, sialyloligosaccharides, and mixtures thereof.
    Type: Grant
    Filed: November 28, 1988
    Date of Patent: February 18, 1992
    Inventors: Howard C. Krivan, Victor Ginsburg, David D. Roberts
  • Patent number: 5084389
    Abstract: A novel bioadsorption composition suitable for removing heavy metal from waster water effluent, the composition comprising a biomass encapsulated sol-gel matrix. A process for preparing the biomass encapsulated sol-gel matrix is also provided. The bioadsorption composition may be suitably used to remove a substantial amount heavy metal (such as uranium) from a waste water effluent, particularly a dilute aqueous stream comprising a waste water effluent (such as mine water). Heavy metal may then be recovered from the bioadsorption composition, thereby rendering the latter as reusable.
    Type: Grant
    Filed: August 1, 1989
    Date of Patent: January 28, 1992
    Assignee: Her Majesty in Right of Canada as represented by the Minister of Energy, Mines and Resources Canada
    Inventors: V. I. Lakshmanan, R. G. L. McCready
  • Patent number: 5084350
    Abstract: Method for encapsulating biologically active material within a semipermeable capsule wherein gelled beads are obtained by suspending the material in a solution of a water-soluble substance which can be reversibly gelled, forming the solution into droplets and gelling the droplets to produce discrete shaped-retaining temporary gelled beads.
    Type: Grant
    Filed: February 16, 1990
    Date of Patent: January 28, 1992
    Assignee: The Royal Institution for the Advance of Learning (McGill University)
    Inventors: Thomas M. S. Chang, Harry Wong
  • Patent number: 5082550
    Abstract: An electrochemical sensor electrode is formed from an electronic conductor coated with a casting solution containing a perfluorosulfonic acid ionomer and a selected enzyme. The selected enzyme catalyzes a reaction between a predetermined substance in a solution and oxygen to form an electrochemically active compound that is detected at the electronic conductor. The resulting perfluorosulfonic acid polymer provides a stable matrix for the enzyme for long lived enzyme activity, wherein only thin coatings are required on the metal conductor. The polymer also advantageously repels interfering substances from contacting the enzyme and contains quantities of oxygen to maintain a sensing capability during conditions of oxygen depletion in the sample. In one particular embodiment, glucose oxidase is mixed with the perfluorosulfonic acid ionomer to form an electrode for glucose detection.
    Type: Grant
    Filed: December 11, 1989
    Date of Patent: January 21, 1992
    Assignee: The United States of America as represented by the Department of Energy
    Inventors: Judith Rishpon, Thomas A. Zawodzinski, Shimshon Gottesfeld
  • Patent number: 5079153
    Abstract: A process for the preparation of an organic ester of ascorbic acid or erythorbic acid represented by the general formula (II) or (III): ##STR1## wherein R.sub.1 is alkyl, aralkyl, or aryl, by reacting ascorbic acid or erythorbic acid with an organic acid or an ester thereof of the general formula (I) :R.sub.1 COOR.sub.2 (I)wherein R.sub.1 is as defined above and R.sub.2 is hydrogen, methyl, ethyl or propyl, in an organic solvent in the presence of an ester hydrolase.
    Type: Grant
    Filed: June 1, 1990
    Date of Patent: January 7, 1992
    Assignee: Mitsubishi Rayon Co., Ltd.
    Inventors: Kanehiko Enomoto, Takao Miyamori, Akihiro Sakimae, Ryozo Numazawa
  • Patent number: 5077217
    Abstract: This invention relates to novel methods for facilitating the enzymatic resolution of racemic mixtures of esters, which are derivatized with groups which enhance the esters' aqueous solubility, in an extractive member reactor where the enzyme is placed alternatively either (1) in the aqueous phase, (2) in association with the membrane, or (3) in the aqueous phase and in association with the membrane, wherein the aqueous ester phase is contacted with one side of the membrane, and where an organic extractive phase is contacted with the other side of the membrane, wherein the extractive phase serves to remove the resolving reaction product. Of particular significance regarding this invention is its use of water soluble esters that are derivatized with groups which enhance their aqueous solubility and their reactivity with enzymatic resolving methods which are mediated in an aqueous environment.
    Type: Grant
    Filed: April 7, 1988
    Date of Patent: December 31, 1991
    Assignee: Sepracor, Inc.
    Inventors: Stephen L. Matson, Stephen A. Wald, Charles M. Zepp, David R. Dodds
  • Patent number: 5073491
    Abstract: Method and apparatus are provided for immobilizing and growing cells in airlift bioreactors to obtain increased cell density. Cells are immobilized by forming alginate beads containing cells and gelatin particles, and dissolving the gelatin by heating to form cavities in the beads entrapping the cells. In a growth chamber of an airlift bioreactor, introduced oxygen-containing gas circulates growth medium in contact with the beads resulting in oxygen transfer to cells in the cavities of the beads where growth of the cells occurs. Preferably, bead formation is carried out in the growth chamber by dripping an alginate-cell gelatin suspension into a calcium solution contained in the growth chamber. Growth medium is then supplied to the chamber, and oxygen-containing gas is introduced to result in circulation of the growth medium and growth of the cells.
    Type: Grant
    Filed: December 23, 1988
    Date of Patent: December 17, 1991
    Assignee: Hoffman-La Roche Inc.
    Inventor: Philip C. Familletti
  • Patent number: 5071747
    Abstract: A porous polymeric support for biological cells is prepared having a total pore volume of at least 75% formed by a plurality of voids having an average diameter within a range of from 1 and 150 .mu.m interconnected by holes. The support is prepared by forming an emulsion containing monomers and/or prepolymers in a continuous phase and having an internal phase that forms the voids of the support, and polymerizing the monomers and/or prepolymers in the continuous phase. The emulsion may be a water-in-oil emulsion with the monomers and/or prepolymers in the oil. Biological cells are introduced into at least the voids of the support. Preferably, the voids have an average size 3 to 15 times the cell size and the holes have an average size 1 to 8 times the cell size. A compound may be produced by passing reactants into the voids via the interconnecting holes to contact the cells in the voids to cause the cells to produce the compound.
    Type: Grant
    Filed: December 22, 1988
    Date of Patent: December 10, 1991
    Assignee: Unilever Patent Holdings B.V.
    Inventors: David B. Hough, Kevin Hammond, Christine Morris, Rober C. Hammond
  • Patent number: 5071909
    Abstract: The invention pertains to a method for immobilizing proteins or peptides onto a flat, microporous membrane surface in a form suitable for sequence analysis or other chemical or enzymatic processes. The process involves the formation of a thin polymer network that entraps the protein or peptide therein.
    Type: Grant
    Filed: July 26, 1989
    Date of Patent: December 10, 1991
    Assignee: Millipore Corporation
    Inventors: Darryl J. C. Pappin, James M. Coull, Hubert Koester
  • Patent number: 5070019
    Abstract: Immobilized yeast for the production of alcoholic beverages is produced by forming calcium alginate beads containing yeast, hardening the beads for 30 to 180 minutes in a CaCl.sub.2 solution, washing the beads for 100 to 500 minutes at 5.degree. to 35.degree. C. with water which may have a salt content of up to 0.5 g/l and drying the beads at a temperature of 10.degree. to 50.degree. C. The immobilized yeast is particularly suitable for use in the bottle fermentation of sparkling wine.
    Type: Grant
    Filed: March 7, 1990
    Date of Patent: December 3, 1991
    Assignee: Huels Aktiengesellschaft
    Inventor: Frank Hill
  • Patent number: 5068104
    Abstract: Methods and compositions are disclosed for vaccinating warm-blooded animals against coccidiosis utilizing suspensions of excysted coccidial sporozoites in physiologically balanced medium containing water-soluble polymeric stabilizers selected from gels, gelatins, polysaccharide gums, cellulose or cellulose derivatives which extend viability or storage, additional extension of viability in storage being attained when the suspensions are finely divided and the polymeric stabilizers are hardened to form microcapsules.Prior to administration, the microcapsule is treated with a chelating agent in order to provide greater efficiency and speed of sporozoite release from the microcapsule and thus improved innoculation against oocyst challenge when compared with microcapsules which have not been treated with a chelating agent.
    Type: Grant
    Filed: August 1, 1988
    Date of Patent: November 26, 1991
    Assignee: A. H. Robins Company Incorporated
    Inventors: Balbir S. Bhogal, Michael G. Williams, Glenn A. Miller
  • Patent number: 5057421
    Abstract: An enzyme reactor system is provided based on the entrapment of a coenzyme-requiring enzyme, a coenzyme, and a regeneration enzyme in a hydrogel layer coated on a support, and confined by an ultraporous thin film semipermeable membrane. The diffusion barrier confines the coenzyme-requiring enzyme, coenzyme, and regeneration enzyme but lets substrate and reaction products, exclusive of coenzyme, diffuse freely into and out of the hydrogel layer. In an alternate embodiment, the support is formed of an ultraporous thin film semipermeable membrane on a microporous or macroporous support, through which the reaction products, exclusive of coenzyme, can diffuse freely, but through which neither coenzyme-requiring enzyme, coenzyme, regeneration enzyme, nor substrate can pass. In this embodiment, the product is recovered in high purity, free of substrate, coenzyme-requiring enzyme, coenzyme, and regeneration enzyme.
    Type: Grant
    Filed: April 7, 1989
    Date of Patent: October 15, 1991
    Assignee: Brunswick Corporation
    Inventors: Frieder K. Hofmann, Wolfgang J. Wrasidlo
  • Patent number: 5055390
    Abstract: A process for the chemical manipulation of liquid and gel microdroplets is disclosed. The process involves providing first microdroplets having aqueous interiors, such that the first microdroplets are surrounded by a non-aqueous fluid. The aqueous interior chemical composition of the first microdroplets is then manipulated by exposure to compounds soluble in both the non-aqueous and aqueous phases, or by exposure to emulsions or suspensions of second microdroplets such that contact between the first and second microdroplets is made. This allows chemical manipulation to be accomplished without removing the first microdroplets from a non-aqueous fluid environment.
    Type: Grant
    Filed: April 22, 1988
    Date of Patent: October 8, 1991
    Assignee: Massachusetts Institute of Technology
    Inventors: James C. Weaver, Gregory B. Williams, Jonathan G. Bliss
  • Patent number: 5051362
    Abstract: Enzyme-occluding polymer particles are produced by a method including the steps of dissolving an enzyme in an aqueous solution of poly(vinyl alcohol) possessing a styrylpyridinium group or a styrylquinolinium group, spray drying the aqueous solution, and exposing the resultant dry particles to an actinic ray, thereby photo-crosslinking the particles.
    Type: Grant
    Filed: March 13, 1989
    Date of Patent: September 24, 1991
    Assignee: Agency of Industrial Science & Technology Ministry of International Trade & Industry
    Inventors: Tetsuro Suehiro, deceased, Kunihiro Ichimura
  • Patent number: 5049494
    Abstract: An economical method of converting mannose to fructose uses a mannose isomerase from Pseudomonas cepacia immobilized on an alumina containing polyethyleneimine crosslinked with an excess of glutaraldehyde. The method utilizes mannose-containing aqueous solutions as the feedstock, and affords solutions in which at least 55% of the mannose has been converted to fructose. Because of the relatively higher levels of fructose than can be obtained by isomerizing glucose to fructose using glucose isomerase, substantial savings in separation of high fructose-containing products can be achieved. The process described represents the first economical mannose isomerase process.
    Type: Grant
    Filed: February 8, 1989
    Date of Patent: September 17, 1991
    Assignee: Allied-Signal Inc.
    Inventor: Paul Allenza
  • Patent number: 5043280
    Abstract: A sterile product containing a substance embedded in a carrier is produced by use of a supercritical gas. In one embodiment, a mixture is formed of a substance, carrier and supercritical gas such as nitrous oxide or carbon dioxide, and the supercritical gas is separated from the substance and carrier to obtain the product. In another embodiment, the supercritical gas contains the substance, and is mixed with an atomized organic solvent containing the carrier to form a mixture. The supercritical gas extracts the solvent, and is separated from the substance and carrier to produce the product. Alternatively, the carrier can be in the supercritical gas and the substance in the solvent, or both the substance and carrier can be in the solvent. Atomization and formation of the mixture can be carried out by feeding the supercritical gas and solvent through a nozzle into a spray tower or column.
    Type: Grant
    Filed: December 21, 1988
    Date of Patent: August 27, 1991
    Assignee: Schwarz Pharma AG
    Inventors: Wilfried Fischer, Bernd W. Muller
  • Patent number: 5037740
    Abstract: Novel immobilized cells are prepared by immobilizing cells of at least one aerobic microorganism and cells of at least one anaerobic microorganism in a single gel immobilizing carrier. The immobilized cells are utilized in a fermentation method. Many useful fermentation products can be readily and economically obtained by using the immobilized cells which accommodate both aerobic and anaerobic metabolic function simultaneously.
    Type: Grant
    Filed: June 25, 1985
    Date of Patent: August 6, 1991
    Assignee: Asama Chemical Co., Ltd.
    Inventors: Hideo Tanaka, Hiroshi Kurosawa, Mizuo Yajima
  • Patent number: 5036000
    Abstract: A system for quantitative colorimetric analysis of biological fluids or organic compounds, including NAD(P)H, or a substrate of an enzyme which reacts with the formation or consumption of NAD(P)H. Concentrations of organic substrates for example alcohol, cholesterol, uric acid, in a biological fluid such as saliva, blood or urine may be determined. The system gives a digital reading of the organic material the concentration which is sought to be determined; the concentration of NAD(P)H is determined by a color change or color "signal" when the NAD(P)H is above a threshold concentration and by the absence of a color signal when the concentration of NAD(P)H is below the threshold concentration. The system includes a chromogen, an electron-accepting reactant which, until exhausted, prevents a visible color change due to accumulation of reduced chromogen, and a catalyst.
    Type: Grant
    Filed: July 20, 1987
    Date of Patent: July 30, 1991
    Assignee: Enzymatics, Inc.
    Inventors: John L. Palmer, Marsha W. Timmerman
  • Patent number: 5034324
    Abstract: A hydrated gel of high water content and high porosity containing an immobilized microorganism is prepared by dropwise addition of an aqueous solution containing a microorganism, polyvinyl alcohol and a polysaccharide to an aqueous solution containing polyvalent metal ions to gel the polysaccharide and form spherical gel beads, and subjecting the beads to at least one cycle of freezing and thawing to gel the polyvinyl alcohol. The polysaccharide can be sodium alginate and the polyvalent metal ions can be provided by calcium chloride. Freezing is at a temperature not higher than -5.degree. C., and the cycle of freezing and thawing is preferably repeated at least two times.
    Type: Grant
    Filed: July 26, 1988
    Date of Patent: July 23, 1991
    Assignee: Kuraray Company, Ltd.
    Inventors: Atushi Shinozaki, Kunio Abe
  • Patent number: 5034428
    Abstract: A method of biomolecule immobilization is described in which the biomolecule itself or, alternatively, a monomer-conjugated biomolecule, is grafted with free monomer onto a hydrophilic, solid-phase, polymeric substrate which has been pre-irradiated with ionizing radiation. The pre-irradiation step is carried out, preferably at -78.degree. C. in air, while the grafting step is carried out at 0.degree. C. in a substantially oxygen-free atmosphere. The technique is applicable to immobilization of a wide variety of biomolecules, such as enzymes, catalysts, hormones, lectins, drugs, vitamins, antibodies, antigens, nucleic acids, DNA and RNA segments, pesticides, dyes and fertilizers. The products may be used for therapeutic or diagnostic applications or bioseparations.
    Type: Grant
    Filed: May 4, 1989
    Date of Patent: July 23, 1991
    Assignee: Board of Regents of the University of Washington
    Inventors: Allan S. Hoffman, Liang C. Dong
  • Patent number: 5034330
    Abstract: A selectively permeable membrane for an enzyme electrode is prepared by forming a mixture of an emulsion of resin containing at least one prepolymer or monomer having ethylenic unsaturation, and a water-soluble polymer material, and subjecting the mixture to irradiation with ionizing or ultraviolet irradiation. The membrane is permeable to substances produced by an enzyme reaction while preventing the permeation of higher molecular weight materials. An immobilized enzyme membrane is formed on an outer surface of the permeable membrane, and the resultant membrane is mounted on an electrically conductive base to form an enzyme electrode. In another embodiment, the selectively permeable membrane is formed on the electrically conductive base, and then the immobilized enzyme membrane is formed. The selectively permeable membrane is situated between the immobilized enzyme membrane, which is in contact with a sample solution, and the electrically conductive base.
    Type: Grant
    Filed: January 24, 1989
    Date of Patent: July 23, 1991
    Assignee: Kanzaki Paper Mfg. Co., Ltd.
    Inventors: Tsunefumi Yamori, Eiji Yuasa, Ryuzo Hayashi
  • Patent number: 5028657
    Abstract: The present invention relates to a method of immobilizing proteins on a polymeric matrix by means of plasma activation and an apparatus and process for the use of such material. The protein mixture is applied to the surface of the polymeric matrix with or without the addition of a crosslinking agent. If is then placed into a plasma generator, wherein the functional groups on both the protein and the matrix molecules are activated to form free radicals. Upon returning from their high energy state, the free radicals form covalent bonds between the proteins and between the protein and the polymeric matrix. Using this method, the proteins are nonspecifically immobilized on the surface of the polymeric matrix. The method can be utilized to immobilize proteins on the surface of polymeric membranes, polymeric beads, polymeric tubes and polymeric plates. The immobilized protein has high biological activity and stability.
    Type: Grant
    Filed: July 18, 1988
    Date of Patent: July 2, 1991
    Assignee: Industrial Research Technology Institute
    Inventors: Tien-Tsai Hsu, Mann-Tchao Wang, Kuang-Pin Hsiung, Ging H. Hsiue, Min-Shyan Sheu
  • Patent number: 5028339
    Abstract: A method for holding a reactant in a polymer includes combining reactant, hydrogel monomer and a quenching surrogate in a solvent, whereby the solvation of the reactant and the monomer is reduced. The monomer is then polymerized to form a polymer matrix formed around the reactant with sufficient intimacy to replicate the molecular shape of the reactant without chemically attaching to or embedding the reactant. The reactant remains accessible for reaction. More than one reactant may be retained by a polymer matrix. The polymer matrix retaining the reactant is also described. The polymer matrix may be sorbed on a substrate, coated on a substrate, cast into shapes or otherwise made available for reaction.
    Type: Grant
    Filed: February 9, 1990
    Date of Patent: July 2, 1991
    Inventor: William T. Clark, III
  • Patent number: 5021350
    Abstract: This invention relates to a process of inclusion of microorganisms of the group consisting of mycorrhizae and actinorhizae in a polymer gel matrix to prepare a solid, stable, storable preparation suitable for use in particular for agronomic purposes. The polymer gel matrix is based on at least one polymer from the polysaccharide group, with at least partial cross-linking of the polymer.
    Type: Grant
    Filed: June 8, 1989
    Date of Patent: June 4, 1991
    Assignee: Rhone-Poulenc Industries
    Inventors: Gerard Jung, Jacques Mugnier, Yvon Dommergues, Hoang G. Diem
  • Patent number: 5021345
    Abstract: Lipase is immobilized by mixing a substrate, a crude porcine pancreatic lipase, an aqueous buffer solution at pH 5-9 and one or more water-soluble polyhydric aliphatic alcohols having from 2 to 6 carbon atoms and from 2 to 6 hydroxyl groups at a temperature of from 0.degree. to 40.degree. C. to form a mixture, allowing the mixture to stand for from 1 minute to 3 days, filtering the mixture to produce a filter cake and washing the cake to obtain the immobilized lipase. The substrate is a pulverulent, insoluble, only slightly swellable copolymer of one or more N-vinyllactams of 4 to 6 carbon atoms with a cyclic amide which contains two or more ethylenically unsaturated, copolymerizable groups, one or more of which are bonded directly to amide nitrogen. The polyhydric aliphatic alcohol can be combined with one or more water-soluble monohydric alcohols having from 1 to 4 carbon atoms.
    Type: Grant
    Filed: November 4, 1988
    Date of Patent: June 4, 1991
    Assignee: BASF Aktiengesellschaft
    Inventors: Dieter Urban, Wolfgang Ladner, Axel Paul
  • Patent number: 5017501
    Abstract: A dispersion of a uniformly sized population of multilamellar lipid vesicles (liposomes) encapsulating an aqueous liquid is prepared by forming a dried film of lipids on the walls of a vessel, contacting the film with an aqueous liquid in the presence of spherical contact masses such as glass beads and agitating. The liposomes have mean diameters in the range of about 150 to about 3000 nanometers and the contact masses have mean diameters of about 50 to 3,000 microns. The aqueous liquid encapsulated may contain enzymes, drugs or marker substances such as colorimetric or fluorescent dyes. A member of a immunological binding pair may be associated with the surfaces of the liposomes for carrying out immunoassays. This method allows for the use of small quantities of marker and lipid, leaves no residual solvents, allows for contact with only glass surfaces and involves no transfer of liposome preparations from lipid film drying vessels to sizing apparatus.
    Type: Grant
    Filed: January 19, 1989
    Date of Patent: May 21, 1991
    Assignee: Abbott Laboratories
    Inventor: Martin Wong
  • Patent number: 5015576
    Abstract: Particles which enclose cavities can be produced by adding a water-insoluble solid, liquid or gaseous cavity generating compound to an aqueous solution of matrix material. Subsequent to forming particles by dispersion in a water-insoluble dispersion medium, the matrix is rendered insoluble in water by cooling, by covalent cross-linking or by polymerization. The cavity generating compound is washed out, whereafter the particles can be used as ion exchangers in gel filtration processes, in hydrophobic chromatography or in affinity chromatography, optionally subsequent to derivatizing the particles. The particles can also be used to advantage as microcarriers in the cultivation of anchorage-dependent cells.
    Type: Grant
    Filed: October 28, 1987
    Date of Patent: May 14, 1991
    Inventors: Kjell Nilsson, Klaus H. Mosbach
  • Patent number: 5015388
    Abstract: A device for biospecifically purifying a liquid having a first portion containing cellular elements and a second portion without cellular elements, the device comprising a casing, a duct for conducting the liquid into the casing, a filter disposed within the casing for tangentially filtering the liquid to separate first portion from the second portion, a filter disposed within the casing for transversely filtering the separated second portion to biospecifically purify the liquid after the separation of the cellular elements, ducts for evacuating the first portion and second portion from the casing.
    Type: Grant
    Filed: March 24, 1989
    Date of Patent: May 14, 1991
    Assignee: Hospal Industrie
    Inventors: Christian Pusineri, Michel Cronenberger
  • Patent number: 5010005
    Abstract: Whole cells of methylotrophic yeasts are able to oxidize benzyl alcohol to benzaldehyde in aqueous reaction media. However, the low water solubility of the reactant and product of this bioconversion, combined with the ability of both to strongly inhibit the reaction, suggested to us the use of non-aqueous reaction fluids. Using non-aqueous systems, it was found that Pichia pastoris can be used to oxidize higher alcohols. The alcohol oxidase from such yeast had been previously reported unable to oxidize such alcohols. Purified alcohol oxidase was shown to function in a number of two-phase systems of varied aqueous to organic phase concentrations. The stability and biocatalyst recovery of the enzyme was improved by immobilization.
    Type: Grant
    Filed: April 24, 1990
    Date of Patent: April 23, 1991
    Inventors: Sheldon J. B. Duff, William D. Murray
  • Patent number: 5010004
    Abstract: A water-soluble substrate and an oily substrate are continuously reacted with immobilized lipase in a reaction vessel having vertically maintained apart upper and lower conically-shaped regions, respectively, for separation of a water-soluble product and an oily product, a plurality of lipase reaction zones each containing immobilized lipase capable of being fluidized and an agitating means, and a plurality of intermediate separation zones for separation of an oily substance and a water-soluble substance. The lipase reaction zones and the intermediate separation zones are disposed alternately between the upper and lower conically-shaped separation regions. Boundaries between the lipase reaction zones and intermediate separation zones are pervious to liquid but impervious to the immobilized lipase.
    Type: Grant
    Filed: October 11, 1988
    Date of Patent: April 23, 1991
    Assignees: Agency of Industrial Science & Technology, Ministry of International Trade & Industry
    Inventors: Yoshitsugu Kosugi, Hideoki Tanaka, Hideo Suzuki, Masaru Shiraki
  • Patent number: 5000955
    Abstract: Thermally reversible polyurethane hydrogels are formed by adding water to a gel forming hydrophilic polyurethane polymer produced by reacting under anhydrous conditions a non-aromatic organic diisocyanate with a glycol component in an NCO/OH mole weight ratio of from about 0.900/1 to about 0.980/1, the glycol component having a number average molecular weight of from about 1000 to 3500 wherein the percentage by weight of the diisocyanate in the reaction mixture is from about 7% to about 20%. The hydrogels are solids at room temperature but liquify at higher temperatures such as body temperature and therefore are useful as carriers for the protection, delivery and sustained release of a variety of active agents including pharmaceuticals, cosmetics, living cells and organisms.
    Type: Grant
    Filed: July 23, 1990
    Date of Patent: March 19, 1991
    Assignee: Tyndale Plains-Hunter Ltd.
    Inventors: Francis E. Gould, Christian W. Johnston, George E. Seems
  • Patent number: 5000966
    Abstract: Ethyl carbamate in an alcoholic liquor is decomposed by contacting the alcoholic liquor with a culture broth or processed matter thereof obtained from a microorganism which belongs to the genus Gluconobacter, Flavobacterium, Arthrobacter, Achromobacter, Alcaligenes, Pseudomonas, Klebsiella, Rhodotorula, Rhodosporidium, Trichosporon or Candida, and is capable of decomposing ethyl carbamate. The alcoholic liquor is improved in quality, and has a low ethyl carbamate content.
    Type: Grant
    Filed: December 9, 1988
    Date of Patent: March 19, 1991
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Yasuhiro Sumino, Shigeya Kakimoto, Shun-ichi Akiyama
  • Patent number: 4999295
    Abstract: A silk fibroin membrane containing an entrapped biocatalyst such as an enzyme or microorganism is provided by forming a mixture of a biocatalyst solution and a silk fibroin solution, forming a membrane by casting the mixture, drying the membrane and mechanically treating the resultant membrane at a temperature and humidity to produce the membrane in .beta.-form and to structurally stabilize the membrane. Mechanically treating may be by stretching or compressing. A biocatalyst sensor is formed by coating an electrically conductive substrate with a gas-permeable layer and coating the gas-permeable layer with the silk fibroin membrane containing an entrapped biocatalyst.
    Type: Grant
    Filed: April 1, 1988
    Date of Patent: March 12, 1991
    Assignee: Terumo Kabushiki Kaisha
    Inventors: Tetsuro Asakura, Makoto Demura, Takeshi Kuroo
  • Patent number: 4997443
    Abstract: A transplantable artificial tissue matrix structure containing viable cells which is suitable for insertion into the body is made by polymerizing precursors in an aqueous solution to form a shape retaining solid matrix comprising viable cells, matrix polymer and reversible gel polymer. The solution contains a matrix polymer precursor, a reversible gel polymer precursor, and viable cells. The reversible gel polymer is dissolved and removed to yield an insoluble, porous matrix containing viable cells. The conditions and reagents are selected to maintain the viability of the cells. The invention is particularly suitable for artificial transplant matrix tissue containing pancreatic islet cells.
    Type: Grant
    Filed: December 4, 1989
    Date of Patent: March 5, 1991
    Assignee: Hana Biologics, Inc.
    Inventors: Bennie J. Walthall, Yvonne E. McHugh, Houston F. Voss
  • Patent number: 4994388
    Abstract: A microcarrier bead system for culturing anchorage-dependent cells is formed of a polystyrene core with a coating of collagen fixed thereover. In certain embodiments, the coating is a protein, such as laminin or fibronectin. The microcarrier bead is of low density, illustratively 1.02 g/cc, and therefore requires less agitation of the nutrient media to maintain suspension. This reduced stirring causes lower shear forces to impinge upon the cells, thereby improving the attachment and proliferation of the cells being cultured. The microcarrier bead of the present invention exhibits surprising advantages with respect to cell attachment and harvesting over beads formed entirely of collagen, or of DEAE-dextran coated with collagen. During harvesting, contamination of the product resulting from dissolved collagen, particularly when proteolytic enzymes are used, is minimized. Additionally, adsorption of toxins and product by the subject microcarrier beads is minimized.
    Type: Grant
    Filed: April 15, 1988
    Date of Patent: February 19, 1991
    Assignees: Solohill Engineering, Inc., The University of Michigan
    Inventors: William J. Hillegas, James Varani, David L. Helmreich
  • Patent number: 4988443
    Abstract: A hollow fiber membrane bioreactor process for continuous selective removal of organic toxicants or other oleophilic solutes present in an aqueous process stream wherein low concentration levels of said toxicant are removed from the aqueous process stream by being extracted and concentrated by the permeably selective hollow fiber membrane and then provided to a microorganism for metabolization into a water soluble metabolite. The water soluble metabolite is prevented from reentering the aqueous process stream and removed from the bioreactor in the aqueous nutrient effluent stream.
    Type: Grant
    Filed: July 3, 1990
    Date of Patent: January 29, 1991
    Assignee: North Carolina State University
    Inventors: Alan S. Michaels, Steven W. Peretti, Christopher J. Tompkins
  • Patent number: 4987075
    Abstract: The inventive membrane of high selectivity comprises a laminated enzyme membrane, which is enclosed by two cellulose membranes. The laminated enzyme membrane is an enzyme-containing polyurethane layer; the cellulose membranes are coated with cellulose nitrate.The inventive process is characterized in that ferricyanide or hydrogen peroxide is added in the presence of peroxidase to the measurement sample, the measurement portion or the enzyme membrane.
    Type: Grant
    Filed: July 19, 1990
    Date of Patent: January 22, 1991
    Assignee: Akademie der Wissenschaften
    Inventors: Jurgen Nentwig, Frieder Scheller, Gunter Hanke, Wolfgang Breitmoser, Hartmut Weise, Dorothea Pfeiffer, Anette Nunchert, Florian Schubert, Christoph Meiske, Siegfried Kuhnel
  • Patent number: 4983524
    Abstract: An enzyme is immobilized by contacting the enzyme with a support in a solution containing an iridoid aglycone cross-linking agent. The cross-linking agent may be genipin or an aglycone or an iridoid glycoside such as geniposide, gardenoside or geniposide acid.
    Type: Grant
    Filed: December 21, 1987
    Date of Patent: January 8, 1991
    Assignee: Suntory Limited
    Inventors: Shigeaki Fujikawa, Kunimasa Koga, Tomoko Yokota
  • Patent number: 4981961
    Abstract: A novel class of compounds, methods for the preparation thereof and the use thereof in chromatographic methods for binding various biologically active materials non-covalently are disclosed. The class of compounds comprises the reaction product of a polymeric gel with a pyridine base, such as 4-dimethylaminopyridine (DMAP), and a halogen-substituted pyridine, such as 3,5-dichloro-2,4,6-trifluoropyridine (DCTFP), which reaction product may in turn be optionally reacted with hydroxyl ions or specified low-molecular-weight compounds. These compounds are capable of selectively and efficiently binding proteins and other organic materials of interest non-covalently to a degree comparable or superior to the heretofore preferred natural affinity ligands, such as Protein A gels. The novel compounds find particular utility in purification and recovery of proteins such as serum albumin and immunoglobulins of various classes from crude sources, such as diluted serum samples from various species.
    Type: Grant
    Filed: September 8, 1989
    Date of Patent: January 1, 1991
    Assignee: BioProbe International, Inc.
    Inventor: That T. Ngo
  • Patent number: 4978619
    Abstract: An immobilized enzyme having an enzyme entrapped in gaps formed in a macromolecular gel matrix is produced by dispersing the enzyme in the form of a fine powder in an organic solvent having dissolved therein a polymerizable monomer, polymerizing the monomer thereby giving rise to a gel matrix, and displacing the organic solvent in the gel matrix with an aqueous solvent.
    Type: Grant
    Filed: August 22, 1989
    Date of Patent: December 18, 1990
    Assignees: Agency of Industrial Science & Technology, Ministry of International Trade & Industry
    Inventors: Shigeru Kajiwara, Hidekatsu Maeda, Hideo Suzuki
  • Patent number: 4963494
    Abstract: An enzyme immobilized membrane comprising an anisotropic ultrafiltration membrane having a porous layer and a dense layer, and an enzyme immobilized therein is disclosed. The porous layer of the ultrafiltration membrane retains a water-soluble polymer having at least two functional groups in the crosslinked state, and the enzyme is covalently bonded to the membrane through the functional groups of the polymer. Preferably, the membrane is prepared from polysulfone. The enzyme immobilized membrane is produced by a process which comprises impregnating a solution of the water-soluble polymer into the porous layer of the ultrafiltration membrane under a pressure of 0.1 to 1.0 kg/cm.sup.
    Type: Grant
    Filed: March 6, 1989
    Date of Patent: October 16, 1990
    Assignee: Nitto Electric Industrial Co., Ltd.
    Inventors: Ken Hibino, Takeshi Okada, Kazuo Nakao, Yuko Sahashi
  • Patent number: 4959148
    Abstract: A method and apparatus for removing and/or modifying specific target substances in the blood is disclosed. The invention includes a column or chamber in which selected bioreactant molecules are suitably retained for reaction within a porous hydrogel polymer matrix by reversibly quenching the reactant propensity with a displaceable surrogate and polymerizing an insoluble cross-linked hydrogel in such manner that the hydrogel polymer replicates the shape of the bioreactant molecule. This replicated phantom shape in the polymer then exhibits profound dispersion-force affinity for the bioreactant. The invention provides for retention of a wide variety of therapeutic reactants and reaction products while confining the reaction within the column.
    Type: Grant
    Filed: January 23, 1989
    Date of Patent: September 25, 1990
    Inventor: William T. Clark, III
  • Patent number: 4959301
    Abstract: A process for rapidly enumerating viable biological entities is disclosed, wherein viability is determined by the critierion of growth of biological entities contained in microdroplets. Alternatively, in some cases, viability is determined by use of vital staining of biological entities contained in microdroplets. The process involves formation of microdroplets, which are very small volume liquid or gel particles, such that some of the microdroplets contain biololgical entities, followed by measurements of biological entities and of microdroplet volumes, such that use of statistical analysis can be used self-consistently to determine the number of viable entities per volume of a sample.
    Type: Grant
    Filed: April 22, 1988
    Date of Patent: September 25, 1990
    Assignee: Massachusetts Institute of Technology
    Inventors: James C. Weaver, Jonathan G. Bliss, Gregory B. Williams, Kevin T. Powell, Gail I. Harrison
  • Patent number: RE33441
    Abstract: Immobilized biologically active material in particle form is prepared by cross-linking with glutaraldehyde and polyazetidine. An aqueous dispersion or solution of biologically active material is partially cross-linked with glutaraldehyde, a wet pasty mass is recovered by dewatering and the mass is sub-divided into discrete particles. A polyazetidine prepolymer is added before, at the beginning or subsequent to partially cross-linking but prior to subdividing the pasty mass into particles, and the prepolymer is allowed to cross-link.
    Type: Grant
    Filed: April 23, 1990
    Date of Patent: November 13, 1990
    Assignee: Novo Industri A/S
    Inventors: Mogens Wumpelmann, Henrik Mollgaard