Abstract: Crosslinked biocompatible compositions comprising an ionically crosslinked component and a covalently crosslinked component for encapsulating biologics are disclosed. In accordance with the present invention, also disclosed are crosslinkable biocompatible mixtures comprising an ionically crosslinkable component and a covalently crosslinkable component. Methods for encapsulating biologics with the crosslinked and cross-linkable biocompatible compositions are provided. Also, retrievable macrocapsules for encapsulating microcapsules or biologics are disclosed.

Abstract: 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.

Abstract: 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.

Abstract: Spherical microcapsules containing biological material such as tissue or living cells are formed with a diameter of less than 300 .mu.m using a microcapsule generating system containing an air knife. The air knife is formed by an air sleeve positioned eccentrically around a needle. An encapsulating material such as an alginate solution containing the biological material to be encapsulated is forced through the needle, while pressurized air is introduced into the air sleeve and flows out an end opening of the sleeve in which the needle is positioned. The pressurized air breaks up the alginate being discharged from the needle. The resultant alginate droplets fall into a collecting tank where they contact a gelling medium, such as CaCl.sub.2, so that the outer surface of these droplets harden and microcapsules are formed. In addition to being eccentrically positioned to facilitate very small droplet formation, the needle preferably has a beveled, pointed discharge end surface to enhance droplet size reduction.

Abstract: An enzyme immobilizing carrier is produced by dissolving low-molecular weight chitosan in an aqueous acid solution and dropping the solution into a basic solution to produce regenerated porous chitosan in particles, reacting the regenerated porous chitosan in particles with the glycidyl ether of an aliphatic polyalcohol, and reacting further the resulting chitosan with the acid halide or acid anhydride of a higher fatty acid in a polar organic solvent. An enzyme and a polyfunctional cross-linking agent are reacted with the carrier to covalently immobilize the enzyme on the carrier. In a preferred embodiment, the enzyme is lipase and the carrier is produced by introducing the glycidyl ether of an aliphatic polyalcohol at 0.01 to 0.4 mole to 1 mole of the pyranose ring residue of the chitosan and by introducing a higher fatty acid having a total carbon number of 6 to 20 at 0.05 to 1 mole to 1 mole of the pyranose ring residue of the chitosan.

Abstract: Encapsulation of active materials in chitosan beads of uniform size and improved mechanical and chemical stability. The active material is suspended in an acidic aqueous solution of a chitosan having a molecular weight of less than 250,000, the suspension is added dropwise to a crosslinking solution of diphosphate and glyoxal hydrate and the resulting beads are cured. It is possible to coat the active material with oil prior to suspension.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Antivenoms to snake, spider, scorpion and jelly fish venoms are produced for the treatment of humans and animals, and for analytical use. The antivenom is purified with an antigen matrix containing a single whole venom or a plurality of whole venoms covalently attached to an insoluble support such as aldehyde-activated agarose. Preferably, the whole venoms forming the plurality of whole venoms are selected from the four whole venoms from C. atrox, B. atrox, C. adamanteus and C. durissus terrificus. A combination of immobilized C. atrox and C. durissus terrificus whole venoms can substantially purify antivenom reactive with all four venoms. The antivenom can be horse or avian such as chicken antivenom.

Abstract: 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.

Abstract: A chelating agent is covalently bonded to a biologically active molecule such as an enzyme or antibody, the biologically active molecule is contacted with a support containing a bound transition metal ion whereby the metal ion is chelated by the chelating agent and the oxidation state of the metal ion is changed by treatment with an oxidizing or a reducing agent to provide a kinetically inert: oxidation state to immobilize the biologically active molecule on the support. The transition metal ion is preferably Co(II), Cr(II) or Ru(III) and the oxidation state of the metal ion is changed to Co(III), Cr(III) or Ru(II), respectively. The chelating agent can be iminodiacetic acid, nitrilotriacetic acid, terpyridine, bipyridine, triethylenetetraamine, biethylenetriamine, 1,4,7-triazacyclonane or a chelating peptide. Certain chelating agents can immobilize more than one biologically active molecule at a metal ion site on the support.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Disclosed are methods for increasing the yield of intact target proteins by cleaving fused polypeptides made by recombinant DNA techniques. The fused polypeptides are designed at the DNA level to have a preselected primary cleavage site in a pendant polypeptide fused to a protein of interest. Structural features of the fused polypeptide and cleavage reaction environment are controlled to favor cleavage by a preselected cleavage agent at the primary cleavage site over a second cleavage agent-sensitive amino acid sequence in the target protein. The cleavage reaction is terminated before completion when the ratio of intact target protein to truncated, cleaved target protein is optimized, and the remaining reaction mixture comprising uncleaved fused polypeptide is resubjected to the cleavage agent. The presence of charged organic molecules in the cleavage reaction mixture favors cleavage at the primary cleavage site. The endopeptidase used for cleavage may be immobilized on an insoluble support matrix.

Abstract: 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.

Abstract: 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.

Abstract: An ionically gellable material is gelled with a metal cation and the metal cation content of the gel is reduced to provide the gel with binding sites not occupied by the metal cation so the gel can be used to bind and remove metal cations from solution. In a preferred embodiment, a calcium alginate gel in the form of beads is prepared, the calcium ion content of the gel is reduced to between 0.01 mg/g and 1.5 mg/g of moist gel by contacting the gel with an aqueous solution of acid such as lactic or tartaric acid having a pH of 1 to 3.5. The gel can be produced containing a microorganism such as yeast used for fermentation so metal ions can be removed while fermenting with the microorganism. In the bottle fermentation of wine to produce champagne, the gel containing yeast is added to the wine in the bottle. During fermentation, calcium and potassium ions are bound by the gel to reduce the precipitation of calcium tartrate and/or potassium bitartrate.

Abstract: A carrier for adhering animal cells during culturing or for immobilization of animal cells is produced by coating a porous substrate with a cell adhesive material in the form of a mixture with chitosan. In a preferred embodiment, the porous substrate is a nonwoven fabric prepared by impregnating a nonwoven fabric web with a binder resin, and the mixture contains silk fibroin, gelatin and chitosan. Coating is carried out by contacting the nonwoven fabric with a solution prepared by adding silk fibroin and gelatin to an acidic aqueous solution of chitosan to coat the nonwoven fabric, drying the coated nonwoven fabric and treating the dried nonwoven fabric with an alkali to render the chitosan insoluble.

Abstract: A native lipase from Mucor javanicus is modified by bonding it to a pectin. The pectin-modified lipase releases fatty acids of identical chain length from a lipidic substrate in a lower saturated-to-unsaturated fatty acid ratio than the native, unmodified, lipase.

Abstract: This granular material consists of a granular porous support bearing negative or positive charges, coated on its surface with a first layer of impregnation with a hydrophilic polymer bearing charges opposite to those of the support, the quantity of said charges present on said polymer being substantially equal to that of the charges present at the surface of the support; and another layer, bound to the first by irreversible chemical coupling, of another hydrophilic polymer which is functional, namely bearing groups endowing said functional hydrophilic polymer with a specific but reversible affinity for at least one biological substance. Among the applications of this material, there are mentioned the separation and purification of antithrombin III and coagulation factors (factors II, VII, VIII, IX, X), and separation of activated coagulation factors (activated factor II, activated factor IX, activated factor X) in solutions containing said non-activated factors.

Abstract: Granules of encapsulated living organisms for controlling agricultural pests are provided having a coating of an invert oil that forms a water-in-oil emulsion and an adsorbent for the oil to make the coated granules free-flowing. The oil slows drying of the organisms to maintain vitality of the organisms. The coated granules are produced by encapsulating bacteria, fungi or nematodes that control agricultural pests in alginate, starch or wheat gluten to form granules, coating the granules with a water-in-oil emulsion of the invert oil, coating the granules with the adsorbent for the oil and drying the coated granules to about 1-10% moisture. The adsorbent can be hydrated silica, fumed silica, clay, bran, diatomaceous earth, zeolite, absorbent starch or mixtures thereof.

Abstract: Myo-inositol in a specimen is assayed by reacting a specimen containing myo-inositol with:a) myo-inositol dehydrogenase using a thio-NADP group or thio-NAD group and an NADP group or NAD group as coenzymes, and which catalyzes a reversible reaction forming myo-inosose from myo-inositol,b ) A.sub.1 andc) B.sub.1to effect a cycling reaction ##STR1## wherein A.sub.1 is a thio-NADP group, thio-NAD group, NADP group or NAD group, A.sub.2 is a reduced form of A.sub.1, when A.sub.1 is a thio-NADP group or thio-NAD group, B.sub.1 is a reduced NADP group or reduced NAD group and when A.sub.1 is an NADP group or NAD group, B.sub.1 is a reduced thio-NADP group or reduced thio-NAD group, and wherein B.sub.2 is an oxidized form of B.sub.1. The change in the amount of A.sub.2 generated or B.sub.1 consumed by the cycling reaction is measured to perform the assay. A composition for performing the assay comprises the above myo-inositol dehydrogenase, as well as the above components A.sub.1 and B.sub.1.

Abstract: A suspension of a microorganism or a plurality of different microorganisms is added to a dispersion of .beta.-chitin gel, and the resultant dispersion is molded and dried to produce an immobilized microorganism such as a film or membrane containing the microorganism. The .beta.-chitin gel dispersion is prepared by isolating and grinding .beta.-chitin from a source such as cuttlefish pen or squid pen, dispersing the ground .beta.-chitin in water and forming a gel dispersion. In forming the gel dispersion, the dispersion of ground .beta.-chitin is gelled and the gel is dispersed in water. Freeze-thawing may be used in gelling the dispersion of ground .beta.-chitin. A film of the immobilized microorganism can be formed on an electrode to prepare a microorganism electrode.

Abstract: Biocidal formulations prepared by: (a) blending predetermined amounts of pre-gelatinized starch, natural starch, biocide such as Bacillus thuringiensis and water to form a mass; (b) drying said mass by heating prepared by with a hot roller at temperatures between 50.degree. and 100.degree. C., preferably between 60.degree. and 90.degree. C., to form a dried mass; and (c) crushing the dried mass to form the final product having the shape of flakes with a diameter preferably less than about 900.mu.. With the method disclosed in the present invention, the process time can be reduced from 24 hours in the prior art to no more than 30 minutes, preferably about 3 to 15 minutes. The present invention represents substantial economic benefits as well as reductions of potential health risks as a result of the reduced contact by operators with biocides during the preparation process.

Abstract: A device for solid phase bacteriological testing is provided having an abbent solid support surface for bacterial culture subdivided into a multiplicity of individual adjacent test areas with lines of an antibacterial composition. The lines may intersect to form a grid may be parallel to form parallel channels, and may be on a sheet of bibulous cellulose which can be impregnated with a bacterial culture. The composition is preferably water-soluble and in the form of an ink containing an aniline dye such as Brilliant Green that is inhibitory to bacteria. The support surface can include a bacterial growth medium or may be supported on a solidifying bacterial growth medium, and the medium may contain agar-agar.

Abstract: The present invention provides a conjugate in essentially pure form comprising a sugar linked to a protein through a peptide linker, wherein said sugar has a reducing terminal and is free of carboxyl groups, and wherein the reducing terminal of said sugar is linked to the peptide linker. The present invention further provides a conjugate in essentially pure form comprising a sugar linked to an enzyme through a peptide linker, wherein said sugar has a reducing terminal and is free of carboxyl groups, and wherein the reducing terminal of said sugar is linked to the peptide linker. The present invention additionally provides a conjugate in essentially pure form comprising a sugar linked to lysozyme through a peptide linker, wherein said sugar has a reducing terminal and is free of carboxyl groups, and wherein the reducing terminal of said sugar is linked to the peptide linker.

Abstract: The invention relates to a method for the targeting of a therapeutic agent to a specific population of cells, wherein a complex is formed between the therapeutic agent and a polysaccharide capable of interacting with a cell receptor, and wherein the resulting complex is internalized into the cell by receptor mediated endocytosis (RME). In one embodiment of the invention, a complex of a therapeutic agent containing iron and the polysaccharide arabinogalactan may be formed and used to deliver iron specifically to hepatocytes by RME.

Abstract: Crosslinked biocompatible compositions comprising an ionically crosslinked component and a covalently crosslinked component for encapsulating biologics are disclosed. In accordance with the present invention, also disclosed are crosslinkable biocompatible mixtures comprising an ionically crosslinkable component and a covalently crosslinkable component. Methods for encapsulating biologics with the crosslinked and crosslinkable biocompatible compositions are provided. Also, retrievable macrocapsules for encapsulating microcapsules or biologics are disclosed.

Abstract: In order to avoid the risk of undesired side reactions of blood products, the latter are produced from plasma by using chymotrypsin to inactivate prekallikrein activator. These preparations are obtained by the fractionated enrichment of plasma proteins, with the proviso that a chymotrypsin solution or immobilized chymotrypsin is added to the fractions at any stage of the fractionation process. Before completion of the preparations, the chymotrypsin or the immobilized trypsin is removed from the preparations.

Abstract: 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.

Abstract: A thermostable premix for use in animal feeds which comprises a carrier material onto which an enzyme solution containing enzymes which are not inherently heat stable are absorbed.

Abstract: A fructose transferring enzyme is immobilized by adsorption on a granular carrier having a primary to quaternary amine. The carrier is preferably an epoxy polymer, a vinyl polymer or a chitosan derivative having a primary, secondary or tertiary amine. Immobilization can be performed without or with a crosslinking agent. The immobilized enzyme is used for producing fructooligosaccharides by passing a sucrose solution through a column containing the immobilized enzyme.

Abstract: Osteoprogenitor cells encapsulated in alginate and alternatively, additionally encapsulated in poly-L-lysine and/or agarose promote regeneration of bone at the site of implantation. The present invention provides a composition comprising osteoprogenitor cells embedded or encapsulated in alginate and the use of said microcapsules for the facilitation of bone regeneration.

Abstract: The reaction of a lipase upon a fatty acid is effected by an improved method which comprises bringing the lipase bonded at multiple points to an anion-exchange residue or a carrier and a carrier having a free anion-exchange group admixed therewith into contact with a reaction mixture containing an oily substance including the fatty acid and a water-soluble substance thereby forming an oily product and a water-soluble product in the reaction mixture and subsequently separating the two reaction products.

Abstract: A process for the continuous conversion of cephalosporin derivatives into glutaryl-7-aminocephalosporanic acid derivativesA process for the continuous conversion of cephalosporin derivatives into the corresponding glutaryl-7-aminocephalosporanic acid derivatives in the presence of a catalyst containing D-amino-acid oxidase is described. The product yield can be increased, where appropriate, by addition of hydrogen peroxide.

Abstract: A bacteria-containing two component polymer gel is provided for solubilizing particulate or colloidal organic materials in wastewater. The gel contains a minor amount of a polymer component that is difficult to solubilize by bacteria in the gel and a major amount of a polymer component that is easier to solubilize by bacteria in the gel. The gel contains bacteria for solubilizing material in wastewater and for solubilizing the gel, and nutrients for the bacteria. The gel also contains a bacteria inhibitor such as sodium sulfide or sodium azide that can diffuse out of the gel at a gel-water interface to allow bacteria to dissolve the gel at the interface while preventing an interior region of the gel from prematurely dissolving. The gel is placed in a housing through which wastewater flows and contacts the gel.

Abstract: An immobilised hydantoinase containing a divalent metal ion selected from Mn.sup.++, Co.sup.++, Fe.sup.++, Ni.sup.++ and Mg.sup.++ is produced that is useful for the preparation of a D(-)(optionally substituted phenyl)glycine or N-carbamoyl derivative thereof by hydrolysis of a 5-(optionally substituted phenyl)hydantoin in the absence of air. Immobilization is carried out in the presence of the metal iona nd the metal ion stabilizes the hydantoinase and renders it capable of repeated re-use. The divalent metal ion may also be added to a reaction mixture containing the immobilized hydantoinase to minimize reduction of hydantoinase activity during hydrolysis of hydantoin. Cells that produce hydantoinase may be immobilized within or on a support, or hydantoinase separated from cells can be adsorbed on a positively charged polymeric support such as an ion exchange resin or covalently bonded to a polymeric support. A cross-linking agent such as glutaraldehyde may be used in immobilization.

Abstract: Aroma and/or flavor materials for use in baking such as in making sourdough bread are produced by culturing lactic acid bacteria in an aqueous dispersion of an expanded, pregelatinized, starch-containing cereal adsorbent. The cereal adsorbent is obtained by extrusion of a cereal product under a pressure of less than 50 bar at a temperature of at least 150.degree. C. A 10 wt% dispersion of the cereal adsorbent has a viscosity at 25.degree. C. of about 30 to about 60 mPas. After culturing, a concentrate substantially free from insoluble matter is separated. The concentrate is separated by centrifugation into a cell concentrate and a clarified broth containing the aroma and/or flavor materials. The lactic acid bacteria are adsorbed in situ onto the cereal adsorbent during culturing. Insoluble residue separated after culturing contains supported lactic acid bacteria that can be used in making sourdough bread. If necessary, the supported bacteria can be dried for storage before use.

Abstract: The invention relates to the field of nutrition and the sugar industry and presents a method and apparatus for producing glucose-fructose liquors on an industrial scale from sugar or liquors thereof. The invention uses reactors packed with a catalyst with high hydrolytic activity, and these are installed within a sugar refining factory or in an industry which dissolves it, such that glucose-fructose syrup is produced in a single operation by a continuous flow of the sugar liquor. High levels of hydrolysis may be attained by modification of the residence time. The process of hydrolysis of the sugar does not significantly alter the color of the solution. The product obtained on an industrial scale can be used both in the food industry and in the pharmaceutical industry.

Abstract: Synthesis of semi-synthetic monobactamic or .beta.-Lactamic antibiotics by using derivatives stabilized by various methods of penicillin G acylase from various microbial sources according to a thermodynamically controlled strategy in monophase water/cosolvent organic apolar systems, wherein the concentration of the cosolvent varies between 30% and 90%, the temperature between -10.degree. C. and 50.degree. C., the pH between 4.5 and 8.5, with concentrations of the antibiotic nucleus between 0.5 an 875 mM and acyl donor between 0.2 mM and 1M, with a relationship antibiotic ring/activated or free acyl donor, using a buffer between 0 and 1M. Application to the pharmaceutical industry.

Abstract: A specific binding pair is bound to an insoluble carrier for use in determining an analyte such as in an immunoassay. The carrier is coated with a first polymer containing a protein polymer having a molecular weight of at least about 20,000 and molecules of a first member of a specific binding pair. A second polymer containing a second member of the specific binding pair is bound to the first member on the carrier by binding of the first and second members of the specific binding pair. The first polymer is preferably more hydrophobic than the second polymer. The protein polymer can be prepared by cross-linking hydrophobic protein molecules of 10,000 to 700,000 molecular weight with a bifunctional or polyfunctional compound to obtain a protein polymer of 200,000 to 20,000,000 molecular weight. The second polymer can be the second member of the specific binding pair or the second member cross-linked with a linker or the second member cross-linked to a hydrophobic protein.

Abstract: A biocatalyst is immobilized with a graft product of a polymer and saponified polyvinyl acetate containing a stilbazolium group as a photo-crosslinking group. The polymer is preferably gelatin, collagen, starch, cellulose, gum arabic, tragacanth gum, carrageenan, mannan, dextrin or alginic acid. The graft product is prepared by bonding the polymer to the polyvinyl acetate, either directly through functional groups of the polymer and polyvinyl acetate or through a crosslinking agent. The polymer provides affinity for the biocatalyst and by grafting the polymer to the saponified polyvinyl acetate, damage to cells upon immobilization is reduced. A liquid composition containing a biocatalyst and the graft product is added to an aqueous solution of an inorganic salt or an organic salt to form a granular gel and the gel is irradiated with actinic rays to cure the gel.

Abstract: A modified solid carrier is used to covalently immobilize biomolecules such as proteins. The carrier is based on well-known matrix materials modified to have covalently bound functional groups of formula I ##STR1## that are suitable for covalent immobilization, where A is a spacer group; X is O, S, or NH and n is 0 or 1. The modified solid carrier is prepared by reacting ammonia with glycidyl groups of a carrier to form .alpha.-hydroxy-.beta.-amino groups, reacting these groups with 2,4,6-trichloro-s-triazine to form an N-triazinyl group-containing carrier, reacting this carrier with ammonia and reacting the resultant carrier with 2,4,6-trichloro-s-triazine.

Abstract: A method for the large-scale cultivation of animal cells wherein animal cells are embedded in a collagen gel which is covered by a protective coating. The protective coating supports and protects the collagen matrix.

Abstract: Carrageenan-immobilized enzymes are prepared that are stable and retain high activity toward substrates when used in substantially water-immiscible organic solvents. The carrageenan-immobilized enzymes are preferably prepared by introducing droplets of an enzyme/carrageenan solution into a chilled alcohol saturated with a potassium salt and hardening the droplets in the alcohol. The alcohol is selected from n-butanol, benzyl alcohol, crotyl alcohol, n-propanol, isopropanol and sec-butanol. Reactions catalyzed by a .kappa.-carrageenan-immobilized esterase include steroselective transesterifications and hydrolysis reactions.