Abstract: Carriers for immobilizing enzymes may be prepared by suspension copolymerizing an oxirane-group-bearing, monovinyl monomer and a major amount of a trivinyl crosslinking monomer having a hydrophilic character, in the presence of a phase separator which does not react with the oxirane group. The resulting carriers, in bead form, have high porosity, high surface area, and pores of diameter sufficient for ready penetration by enzymes and substrates.

Abstract: A process is disclosed for chemically modifying naturally occurring proteins to produce enzyme-like modified proteins. The process comprises partially denaturing a cofactor containing holoprotein by removal of the cofactor to produce a partially denatured cofactorless or so-called apoprotein. The partially denatured protein is contacted with an inhibitor of a selected model enzyme and cross-linked. The resultant protein product is an enzyme-like modified protein having the catalytic characteristics of the model enzyme whose inhibitor is contacted with the partially denatured apoprotein.

Abstract: Immobilized aminoacylase having high specific activity is obtained by covalent bonding of aminoacylase to a partially hydrolyzed Akrilex P type acrylamide-N,N.sup.1 -methylene-bis (acrylamide) copolymer. Covalent bonding is carried out by partially hydrolyzing the copolymer with a base or an acid to form carboxy groups, activating the carboxy groups with a carbodiimide and coupling aminoacylase to the activated carboxy groups. The aminoacylase may be isolated from mammal kidneys by forming an aqueous kidney extract, heat treating the extract and isolating aminoacylase from the heat treated extract.

Abstract: The present invention is directed to novel methods and apparatus for conducting chemical and biological reactions. A reactor is provided that includes a reaction matrix member formed from microporous ceramic. A chemical or biological material is fixed within the pores of the porous matrix, and reaction solution is passed through the porous matrix member at a controlled rate. Preferably, the matrix member is tubular in shape and comprises a plurality of concentric layers of ceramic material, each layer having a substantially uniform pore size, but the plurality of layers having a progressively decreasing pore size with respect to the preceding layer. Each layer may also have a different thickness than other layers. Reaction solution is introduced into an axial bore through the ceramic matrix member, and the product solution is collected from the outside of the ceramic matrix member. Optionally, lumens within one or more adjacent ceramic layers, and/or spaces between layers can be provided.

Abstract: A derivative of a fibrinolytic enzyme in which the catalytic site on the enzyme which is responsible for fibrinolytic activity is blocked by a human protein attached thereto by way of a reversible linking group.

Abstract: The invention relates to a process for the preparation of a cyclodextrine glycosyltransferase enzyme.The immobilization can be carried out by two methods. According to the first method a cyclodextrine glycosyltransferase enzyme is activated with a solution of a carbodiimide compound and the thus treated enzyme is applied in a solution having a pH value of 4.5-8.5 onto a polysaccharide derivative comprising at least 0.1 m-equiv./g of free amino group. According to the second method the enzyme is applied in a solution having a pH value of 4.5-8.5 onto a polymer produced from an acrylic acid and/or methacrylic acid or acrylic amide and/or methacrylic amide monomer by means of a cross-linking agent of the acrylic or allylic type which polymer comprises at least 0.1 m-equiv./g of functional carboxy group, activating the polymer with a solution of a carbodiimide compound and washing and if desired drying the product thus obtained.

Abstract: A nucleic acid-protein conjugate which is specific with respect to a selected living cell is prepared by linking said nucleic acid to a protein specific to said living cell.

Abstract: Immobilized enzyme systems which contain a tea polyphenol-enzyme adduct and the methods for preparing and using such immobilized enzyme systems.

Abstract: A suspension of diagnostic particles comprising antibody molecules attached to a carboxylate derivatized polymer core is provided for agglutination tests. The antibody is linked to the core through an avidin-biotin bridge. Avidin is joined by an amide bond to carboxyl groups on the core, and biotin is linked by an amide bond to amino groups on the antibody molecule. The core-bound antibody is exposed to a mixture of free biotin and biotinylated antibody to attach a controlled amount of antibody that is consistent with suspension stability prior to its use in a test and rapid cross-linking of suspended particles in the presence of antigen.

Abstract: A process is disclosed for the chemical immobilization of biological material such as bacteria and enzymes containing an active hydrogen with a vinyl addition polymer of an isocyanatoalkyl ester of an ethylenically unsaturated carboxylic acid. The vinyl addition polymer is versatile in that it can be copolymerized with varying amounts and types of comonomers.

Abstract: Organic ligands containing at least one primary or secondary amino group or sulfhydryl group are coupled to a polymeric carrier containing at least one hydroxyl group, by activating the polymeric carrier by treatment with 2-fluoro-1-methylpyridinium toluene-4-sulfonate and reacting the activated polymeric carrier with the organic ligand which is thereby bonded directly to a carbon atom of the polymeric carrier. The polymeric carrier can, for example, be a possibly cross-linked polysaccharide and the organic ligand is preferably a biologically active material such as a drug or protein. The coupling product is an affinity matrix which can be used for affinity purification, covalent chromatography and reversible or irreversible covalent immobilization of biologically active molecules. The coupling method can be performed under mild conditions not damaging sensitive molecules.

Abstract: Surface-modified electrodes which may be used in electrochemical cells for production of electrical energy comprise an enzyme immobilized on a support. The support consists of at least a monolayer coating of a carbonaceous pyropolymer possessing recurring units containing at least carbon and hydrogen atoms composited on a high surface area refractory inorganic oxide such that the carbonaceous pyropolymer monolayer coating replicates the surface area and macropore volume of the inorganic oxide. The coated support is then treated by impregnation with a water-soluble polyamine followed by contact with a solution of a molar excess of a bifunctional monomeric material to form a copolymer which provides pendant bonding sites. The copolymer is entrapped and adsorbed in the pores of the support material to provide a permanent attachment thereto. The treated support is then contacted with an excess of an enzyme to effect the conjugate attachment of the enzyme to the treated support.

Abstract: Particle reagents, having polyether polyamine linking groups, for use in turbidimetric immunoassays are provided. These linking agents permit ready covalent attachment of compounds of biological interest to polymer particles and lead to immunoassays of improved precision.

Abstract: Enhanced immunogenicity is achieved by covalently linking immunogens to liposomes and injecting the membrane-bound-proteins into an appropriate vertebrate host. Methods and compositions are provided for producing antibodies.

Abstract: A method to obtain a substantially pure and stable hLH-hCG receptor from gonadal cells is disclosed. The characteristics of the purified receptor are disclosed. The receptor, in addition to being used as receptor in an enzyme- or dye-receptor assay for hLH and/or hCG, can be used to purify hLH or hCG used in the preparation of standard dye-hormone or enzyme-hormone complexes. These complexes can be used in enzyme- or dye-immunoassays, as well as the receptor assay.

Abstract: Immobilized cholinesterase enzyme preparations are prepared by treating a polymeric resin, built up from acrylic acid and/or methacrylic acid and acryl amide and/or methacryl amide monomers with an acryl or allyl type cross-linking agent and containing at least 0.1 meq/g of --COOH functional groups, with a carbodiimide derivative which is soluble in water or is soluble in an organic solvent at temperatures below 0.degree. C., applying a solution of cholinesterase enzyme with a pH of 4.5 to 8.5 to the resulting activated support, washing the resulting product, and drying it if desired.

Abstract: A method for the potentiometric determination of a dextran solution is provided wherein the dextran is enzymatically hydrolyzed to glucose, the glucose is oxidized to form hydrogen peroxide and the hydrogen peroxide is measured utilizing a redox electrode. A novel electrode having a plurality of enzyme impregnated layers is provided for converting the dextran to glucose.

Abstract: This invention provides a urokinase complex adsorbable by fibrin characterized in that it comprises heavy chain of high molecular weight urokinase as coupled with heavy chain of plasmin by one or more S-S bonds and a process for preparing the same.

Abstract: A biocatalyst contains microorganisms, e.g., of the species Arthrobacter simplex, Aspergillus ochraceus, Bacillus sphaericus, Curvularia lunata, Flavobacterium dehydrogenans, Mycobacterium spec., or Saccharaomyces uvarum, immobilized on a copolymer of acrolein and 1-vinyl-2-pyrrolidone, crosslinked by reaction with an alkylenedioxydiamine of the formulaH.sub.2 NO--(CH.sub.2).sub.n ONH.sub.2wherein n is a number of 2 to 12. The preparation of steroids is also disclosed.

Abstract: A protein is immobilized by a simple and effective method on a porous polymeric support by a first soaking in a dilute long-chain cationic solution and a second soaking in a dilute aqueous protein solution. The long chain cationic is preferably a nitrogen compound such as a diamine having at least one alkyl or alkenyl group containing at least eight carbon atoms. A preferred diamine is N-coco-1,3-diamino-propane. The protein may be an enzyme or hormone. A preferred enzyme is catalase or a two enzyme system of catalase and glucose oxidase.

Abstract: Gelatins are crosslinked in a non-anhydrous environment to yield water-swellable, essentially water-insoluble foams. The gelatin is contacted with a polyisocyanate at a pH between about 6 and about 8 and subjected to a high rate of agitation. The process of this invention can be employed to immobilize proteins, enzymes, antibodies, etc.

Abstract: A biospecific adsorbent comprising pyroglutamyl-lysyl-leucyl-argininal combined with a water-insoluble support is provided. This biospecific adsorbent is useful as an adsorbent for use in affinity chromatography and can be utilized for the purification of proteases such as urokinase.

Abstract: This invention discloses a method of immobilizing an enzymatically active material to a water-insoluble polyanion which comprises bringing a polycation-containing aqueous medium and the enzymatically active substance into contact with the water-insoluble polyanion having any desired form. This method is characterized in that the enzymatically active substance is adsorbed on the surfaces of the water-insoluble polyanion and, at the same time, a strong complex is formed by the interaction of the polycation and the polyanion to produce a water-insoluble film. As a result, the enzymatically active substance so adsorbed is securely fixed to the surfaces of the water-insoluble polyanion and scarcely released therefrom.

Abstract: Biological materials are immobilized by being absorbed into vermiculite particles which then are coated with a polymeric coating material. A variety of cross-linking, condensing, and gelling agents may be used to strengthen and crosslink the polymer.

Abstract: There is disclosed a process for producing a covalently attached alpha-1-proteinase inhibitor - water soluble polymer complex useful for pulmonary emphysema therapy, a covalently attached alpha-1-proteinase inhibitor - water soluble polymer complex produced by the process, a composition thereof in a pharmaceutically acceptable carrier, and a method for treating pulmonary emphysema by administering to a human patient a therapeutically effective amount of the complex or preparation.

Abstract: A derivative of a human-originated non-immunogenic plasminogen activator is disclosed which comprises at least one polyalkylene glycol attached with at least one coupling agent to amino acid side chains of said plasminogen activator, said polyalkylene glycol having a molecular weight of 200-20,000 and optionally containing one or more alkyl and/or alkanoyl groups as substituents. Also disclosed are a process for producing such derivative and a thrombolytic agent containing such derivative.

Abstract: Polyalkylenepolyamines are crosslinked in a non-anhydrous environment to yield water-swellable, essentially water-insoluble gels. The polyalkylenepolyamine is contacted with a polyisocyanate at a pH between about 5 and about 8 and subjected to a high rate of agitation. The process of this invention can be employed to immobilize proteins, enzymes, antibodies, etc.

Abstract: An improvement in assaying methods involving biospecific affinity reactions, in which there are used from 2 to 4 reactants, one of which, reactant (I), is labelled with at least one analytically indicatable atom or group and is soluble in the aqueous liquid in which the biospecific affinity reaction is carried out, the reactants forming, by means of biospecific reactions, a conjugate in which labelled reactant (I) is incorporated; and in which assaying methods the analytically indicatable atom or group is assayed in the conjugate and/or in labelled reactant (I), which is not bound to the conjugate. The conjugate that has been formed or labelled reactant (I) not bound to the conjugate is bound covalently to an insoluble carrier or to an insolubilizable carrier, which latter carrier is made insoluble after the covalent binding has been carried out, whereafter the assay of the analytically indicatable atom or group is carried out.

Abstract: A solution of an active protein substance and an inactive protein substance is reacted with a cross-linking agent, optionally in the presence of an inert carrier, under cross-linking conditions to produce articles comprising both active and inactive protein substances. The active protein substance comprises up to about 20 percent, e.g. from 1 to 20 percent by weight, based on the final weight of the total protein substance, whereas the cross-linking agent comprises from 0.5 to 8 percent by weight, based on the weight of the total treated mixture. The obtained articles are in the form of a solution or a suspension in aqueous medium, in the form of a film, in the form of a membrane, in the form of a fabric, in the form of a porous material, or in the form of a mass, such as granules, pills or tablets.

Abstract: The present invention provides liver uricase, wherein it is covalently bond to a water-soluble polysaccharide, polyacid anhydride, polyvinylpyrrolidone or acid anhydride as carrier substance and is still soluble at pH values below 6.The present invention also provides a process for the preparation of this liver uricase.

Abstract: Living, fermentable yeast cells are prepared having an enzyme or mixture of enzymes coupled thereto. Enzyme coupling is carried out by contacting at least partially dehydrated living yeast cells with an aqueous enzyme solution to cause the yeast cells to rehydrate and a layer of enzyme to form on the surface of the yeast cells, and than contacting the rehydrated yeast cells with an enzyme-precipitating solution which optionally contains a cross-linking agent to cause the enzyme to become attached to the yeast cells. An aqueous solution of tannin is preferably the enzyme-precipitating solution and gluardialdehyde is preferably the cross-linking agent. Pepsin coupled to Saccharomyces yeast, when used to ferment grape must to produce wine, results in practically foam-free attenuation, quicker fermentation and better self-clarification. Saccharomyces yeast having amgloglucosidase coupled thereto may be used to ferment beer wort to produce a diet beer.

Abstract: A rapid, specific, serological method for identification of microorganisms is carried out by immunizing a warm-blooded mammal with a killed microorganism to obtain an antisera, conjugating the antisera with an enzyme marker, bonding a microorganism to a solid support, adding the enzyme-conjugated antisera to the bonded microorganism in the presence of a color reactant and identifying the microorganism from the color reaction. Preferably, immunizing is carried out with two injections of about 10.sup.9 killed microorganisms each with the second injection being about 14 to 21 days after the first, and recovering the antisera about 14 to 21 days after the second injection.

Abstract: The instant invention is directed to a process for the production of denatured polyaddition products of biomasses and isocyanates, comprising reacting(A) from 5 to 98%, by weight, based on (A)+(B), of a biomass based on microorganisms or derivative and decomposition products thereof with(B) from 95 to 2%, by weight, based on (A)+(B), of a compound containing isocyanate groups, at temperatures of at least 50.degree. C. with complete denaturing of component (A).

Abstract: An acrylic-acid- based photopolymerizable composition is prepared which is capable of binding bioactive substances after being photopolymerized. The composition may be applied as a coating on a carrier substrate, photopolymerized and a bioactive substance fixed thereto. The composition adheres well to any usual carrier substrates, and its degree of hydrophilicity and permeability can be adapted to needs. The composition contains acrylic acid, a photoinitiator which is an aromatic ketone compound, a photopolymerization activator and adhesion promotor which is an amino-alcohol, acrylate or methacrylate, and a copolymerizable olefinic monomer which contains a reactive functional group capable of binding bioactive substances. The olefinic monomer is preferably N-hydroxysuccinimide acrylate, N-hydroxysuccinninimde amidocaproate, epoxypropyl acrylate or 2-isocyanato-ethyl acrylate.

Abstract: The invention relates to selectively acting polymeric sorbents or saccharides, glycoproteins and saccharide containing polymers. In accordance with the invention, lectins are covalently bonded on vehicles selected from among, oxidized glycosylated hydroxyalkylacrylates or hydroxyalkylmethacrylates, and polyvinyl alcohol. These vehicles are comparable to known materials based on polysaccharides with bonded-on lectins, especially as far as the absorption power of the sorbent is concerned. The preferred process for preparing such sorbents is substantially easier than the hitherto used ones since it does not require specific measures to be taken in the work with highly toxic activating agents, and enables a simple control of conversion degree of the bonding reaction while achieving a relatively high reproducibility. Apart from this, unoxidized saccharide molecules bonded on the vehicle make it hydrophilic, or at least raise its original hydrophility.

Abstract: The present invention relates to novel key intermediates for the production of biologically active compounds coupled to polymers, of the general formula P--NCX.sub.2, wherein X designates a halogen atom selected from chlorine and bromine, and wherein P designates the polymer backbone of a polymer of the polyamide, polyester and ureaformaldehyde type. The invention further relates to compounds obtained by the reaction of the above compound P--NCX.sub.2 with a bifunctional or polyfunctional nucleophile. Suitable nucleophiles are hydrazides of dicarboxylic acids and amongst these there may be mentioned polyacrylamides partially substituted with acylhydrazide groups; polyfunctional amines selected from alkylamines, aralkylamines, arylamines and macromolecular compounds containing amino groups. The key intermediate PNCX.sub.2 may be coupled directly to biologically active macromolecules and amongst the preferred compounds of this type there are the various biologically active proteins and enzymes.

Abstract: A biochemically active matrix for use in a bio-artificial organ is disclosed. The biochemically active matrix has an enzyme covalently bonded to a matrix of organochemically cross-linked fibrin. The matrix may be suspended in a medium of agarose which irreversibly solidifies below 37.degree. C. The bio-artificial organ is useful for extracorporeal treatment of blood to remove excess substrate from the blood. .

Abstract: Disclosed is a process whereby enzymes are immobilized on activated granular carbon. The process involves treating the carbon with a polyamine compound having pendant amino groups to cause the polyamine to adhere to the carbon leaving pendant amine groups free to further react. The free amine groups are derivatized by treatment with a difunctional compound having amine reactive moieties, so that free amine groups of the enzyme can be covalently bound to the polyamine via the amine reactive compound. By this method, enzymes can be immobilized onto granular carbon which provides a support having excellent physical properties.

Abstract: Immobilization of enzymes is carried out by covering the surface of a solid support with an enzyme and then contacting the enzyme with an immobilizing reagent in the vapor phase. The immobilizing reagent is preferably an aldehyde or a polymerized aldehyde. By having the immobilizing reagent in vapor phase, the immobilizing reagent concentration can be easily controlled by the vapor pressure. Additionally, there is obtained a uniform covering of immobilized enzyme on the support, and support surfaces which are uneven or curved can be covered with immobilized enzyme regardless of size.

Abstract: The invention relates to a method for the preparation of discrete particles containing a biologically active substance comprising discrete particles of support material having immobilized in the pores thereof a biologically active substance (e.g. an enzyme). The method includes precipitating a biologically active substance in the pores of the particles of support material, by use of a precipitating agent comprising or including a water miscible organic liquid, and treating the biologically active substance precipitated in the pores to cause cross-linking so as to immobilize biologically active substance in the pores of the particles or porous support material.

Abstract: The invention describes a polymer particle-protein conjugate and the method of its preparation utilizing polymer particles having reactive surface hydrazide groups and a difunctional compound to bind the protein to the polymer particles in a polymer latex. Products derived from the invention can be used in latex agglutination tests for the detection of pregnancy or for the detection of proteins which may be indicative of disease states.

Abstract: Process for chemically binding organic compounds containing carbohydrate residues, onto a support bearing at least one reactive --NH.sub.2, in which at least one --CH.sub.2 OH group of the carbohydrate residue is transformed in a --CHO group, by oxidation and then the --CHO groups thus obtained are reacted with at least a reactive --NH.sub.2 carried by the side chains covalently bound on a solid, insoluble support, the side chains are chosen from among amines, polyamines, diacids, amino-acids, hydrazines, and are eventually coupled, by the intermediary of their reactive --NH.sub.2, with a nitrogen-containing compound chosen from aliphatic or aromatic amines, aliphatic or aromatic hydrazines, or amino acids, comprising eventually jointly a --SH group and a --NH.sub.2 group.Products resulting from this process and biological reagents containing said products as their active constituents.

Abstract: Support matrices are prepared by titanating the surface hydroxyl groups of refractory inorganic oxides with a titanium tetrahalide, such as TiCl.sub.4, reacting each of the remaining halogens of the surface-titanated oxide with one of the amino groups of diamine, and thereafter reacting the remaining amino group with one of the functional groups of a dialdehyde or diisocyanate. Titanating is carried out by contacting a refractory inorganic oxide with titanium tetrahalide, preferably in the absence of a solvent for the titanium tetrahalide, removing excess and unreacted titanium tetrahalide and heating the titanated inorganic oxide at a temperature of from about 80.degree. C. to about 200.degree. C. in an inert atmosphere of nitrogen, argon or helium, or in a vacuum. Such support matrices may be used to bind enzymes, affording effective immobilized enzyme systems.

Abstract: Biologically active material such as an enzyme is bonded to a carrier containing hydroxyl groups by binding an isocyanate compound to the carrier and bonding the biologically active material to the bound isocyanate compound. Binding of the isocyanate compound to the carrier is achieved with the use of a non-toxic titanium based compound which catalyzes the formation of urethane bonds. The preferred non-toxic based titanium compound is an orthotitanium acid ester such as tetrabutyltitanate.

Abstract: Enzymes are immobilized on a solid support material containing essentially cellulose and lignin by a process involving oxidation of the support to provide aldehyde groups, amination of the oxidized support by reacting a diamine with the aldehyde groups, reduction of the aminated support to produce stabilized aminated groups, activation of the aminated groups by reacting the groups with a dialdehyde and immobilization of an enzyme by covalent coupling of the enzyme to the activated groups of the support. The enzyme may be invertase and the immobilized invertase can be used to treat a sugar syrup.

Abstract: A prosthetic polymer material is made non-thrombogenic by immobilizing apyrase on its surface. Immobilization is preferably carried out by hydrolytically activating the surface of a polyamide polymer or a polyethylene terphthalate polymer, and treating the hydrolyzed polymer with a solution of cross-linking agent and a solution of apyrase. The apyrase converts adenosine diphosphate to adenosine monophosphate and adenosine whereby the formation of thrombi is inhibited.

Abstract: The instant invention is directed to a process for the production of denatured polyaddition products of biomasses and isocyanates, comprising reacting(A) from 5 to 98%, by weight, based on (A)+(B), of a biomass based on microorganisms or derivative and decomposition products thereof with(B) from 95 to 2%, by weight, based on (A)+(B), of a compound containing isocyanate groups, at temperatures of at least 50.degree. C. with complete denaturing of component (A).

Abstract: Sucrose mutase in whole cells of Protaminobacter rubrum #l is immobilized by contacting the cells with tannic acid, polyethylenimine, and an adduct of glutaraldehyde and an epihalohydrin/polyamine copolymer. The resultant reaction product has improved sucrose mutase activity and physical characteristics for use in a packed-bed reactor to convert sucrose to palatinose.

Abstract: An immobilized aminoacylase is prepared by bonding aminoacylase to a water-insoluble porous anion exchanger such as a porous phenolic resin, porous styrene resin, porous silica or porous glass having anion exchange groups and treating the bonded amino-acylase with a crosslinking agent such as an aliphatic dialdehyde. The porous anion exchanger preferably has a pore size of about 150.degree. to 3,000 A.degree., pore volume of about 0.3 to 1.0 m.sup.1 /g, specific surface area of about 10 to 150 m.sup.2 /g and particle size of above 0.1 to 1.2 mm. Preferred anion exchangers are trimethylammonium-introduced styrene resin and trimethylammonium-introduced silica.

Abstract: An improved immobilized enzyme composite is prepared by subjecting a siliceous carrier to an initial treatment with alkali, then acid, then reacting the carrier with an organosilane. The organosilane may then be coupled through a covalent coupling agent with an enzyme. The alkali-acid treatment provides an exceptionally high number of hydroxyl groups per unit volume, so that the treated carrier is especially useful in the preparation of high performance immobilized enzyme compositions, particularly by multi-layering immobilization, providing a very high amount of enzyme activity per unit volume. Multi-layering is accomplished by successive steps of bonding a difunctional covalent coupling agent to a previously immobilized enzyme layer, then bonding an additional layer of enzyme to the coupling agent. This may be repeated to apply as many layers as desired.