Abstract: The present invention is to provide a novel medicine, drink, food or feed having an action of strengthening bone. More specifically, the present invention is to provide a medicine, drink, food or feed combined with collagen, fraction containing collagen or degradation product thereof. Fraction containing collagen was prepared by mincing skin corium layer into pieces, defatting it and lyophylization or by pulverizing bone, decalcifying it and lyophylization. Oral administration of these can stimulate proliferation of osteoblast, inhibit bone resorption and strengthen bone. They can be useful for improvement of osteoporosis, bone fracture, bone pain, etc.

Abstract: Combinations, called matrices with memories, of matrix materials that are encoded with an optically readable code are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The matrix materials may additionally include fluophors or other luminescent moieties to produce luminescing matrices with memories. The memories include electronic and optical storage media and also include optical memories, such as bar codes and other machine-readable codes. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

Abstract: The current invention is a biomedical implant comprising a biomedical matrix material and a biodegradable porosifying agent. As the porosifying agent degrades in situ, an implant with an inter-connecting network is formed. The resultant mechanically stable implant allows for tissue and fluid influx into the matrix. The invention is also directed to a method for repair of mammalian tissue using the above-described implant.

Abstract: Biopolymer matt, biopolymer matt composites, biopolymer matt compositions, and methods of preparing the matt and composite matts are described. Also described are biocompatible constructs which include extracellular matrix macromolecules and methods of preparing these constructs. The matt, matt compositions and biocompatible constructs of the invention can be used in tissue repair and reconstruction.

Abstract: The current invention is a biomedical implant comprising a biomedical matrix material and a biodegradable porosifying agent. As the porosifying agent degrades in situ, an implant with an inter-connecting network is formed. The resultant mechanically stable implant allows for tissue and fluid influx into the matrix. The invention is also directed to a method for repair of mammalian tissue using the above-described implant.

Abstract: An animal collagen or gelatin based crumble, and processes for the preparation of the particulate crumble, are useful in the preparation of collagen or gelatin based compositions. The crumble is prepared by extracting animal collagen from an animal tissue source and combining the collagen with sufficient water to form a composition comprising about 15-45 wt % animal collagen and about 0.01-5 wt % of a stabilizer or preservative. Such a combination of materials can be solidified and then processed into a large particulate format. The large particulate comprises a, regular or amorphous shaped, roughly crumbled or roughly divided, crumble product. The typical particle size of a majority of the crumble is about 0.2-5 cm. The crumble is easily manufactured, packaged, stored, handled and distributed. The crumble can be easily used as is. The material melts easily into a use locus.

Abstract: The present invention is a process for degreasing bone for the manufacture of gelatin. A lipase solution at a concentration of greater than 0.1 ppm is added to a collagen containing material and treated for a time sufficient to solubilize the fat contained in the collagen containing material to produce degreased collagen containing material with a fat content of less than 1 weight percent.

Abstract: An animal collagen or gelatin based crumble, and processes for the preparation of the particulate crumble, are useful in the preparation of collagen or gelatin based compositions. The crumble is prepared by extracting animal collagen from an animal tissue source and combining the collagen with sufficient water to form a composition comprising about 15-45 wt % animal collagen and about 0.01-5 wt % of a stabilizer or preservative. Such a combination of materials can be solidified and then processed into a large particulate format. The large particulate comprises a, regular or amorphous shaped, roughly crumbled or roughly divided, crumble product. The typical particle size of a majority of the crumble is about 0.2-5 cm. The crumble is easily manufactured, packaged, stored, handled and distributed. The crumble can be easily used as is. The material melts easily into a use locus.

Abstract: This invention is directed to an article, such as a medical device, for local delivery of genes. The article comprises a substrate coated with a cross-linked protein. The invention is also directed to a method for coating an article with cross-linked protein. An additive may be optionally incorporated into the coating. The crosslinked protein coating can strongly absorb genes. Thus, the coated article can be used to locally deliver genes to a target site. The coating of the invention exhibits excellent biocompatibility and biodegradability, and does not cause toxicity or side-effects.

Abstract: A conjugate of a synthetic polypeptide containing RGD or (dR) GD and a biodegradable polymer, such as hyaluronic acid or chondroitin sulfate is disclosed. Methods of making the conjugate and using it to aid wound healing by providing a temporary matrix are disclosed.

Abstract: The present invention describes a gelatin having a high molecular weight fraction (>250,000 Daltons) of from 0 to 25 wt %, a beta fraction (150,000-250,000 Daltons) of from 0 to 20 wt % and an alpha fraction (50,000-150,000 Daltons) of from 15 to 55 wt %. The gelatin has a gel strength of from 200 to 400, an absorbance a 420 nm of from 0 to 0.068 and a concentration of protease of greater than 10 ppb.

Abstract: The present invention is a process for the manufacture of gelatin which includes providing a collagen containing material and demineralizing the collagen containing material to produce ossein. The ossein is added to a water solution containing at least 3% sodium hydroxide or potassium hydroxide and at least 3% sodium sulfate for a time sufficient to form a reacted slurry. The reacted slurry is heated to a temperature of at least 45.degree. C. for a time sufficient to solubilize the ossein thereby producing a solution containing gelatin. The pH of the solution containing gelatin is raised to greater than 9.8. The pH of the solution containing gelatin is reduced with a sulfate salt of a divalent or trivalent metal to a neutral pH (between 7.0 and 8.0). The pH of the gelatin solution is then lowered to between 5.0 and 6.0 and a polymeric flocculant is added to the gelatin solution in an amount of less than 0.1% based on the dry weight of the gelatin to form a floc and the floc is removed.

Abstract: In a method for producing gelatin from collagen-containing raw material, the raw material is ground and mixed with water to form a slurry; the slurry is treated with an acid and heated in order to expose the collagen in the raw material; the pH and the temperature of the slurry are adjusted once more; the slurry is separated into a liquid portion and a solid residue; and the gelatin is recovered from the liquid portion.

Abstract: The present invention relates to the development of a modified substrate capture immunoassay useful in the detection of a neutral metalloproteinase enzyme, type IV collagenase. Capture and immobilization of this enzyme can be achieved by coating the microtiter plate with gelatin, an alternative substrate for this enzyme. The captured enzyme can then be detected by affinity purified rabbit anti-type IV collagenase antibodies prepared against synthetic peptides from the amino terminus of the enzyme. Soluble type IV collagenase can readily be detected in samples known to contain this enzyme. Using purified enzyme this assay method can detect less than 50 ng of latent type IV collagenase. Using EDTA, an inhibitor of this metalloproteinase, gelatin binding can be shown to be independent of catalytic activity.

Abstract: The present invention is a biodegradable, reversibly-swellable, polyvalent cation-binding, protein-based hydrogel which comprises an acyl-modified protein matrix in which the acyl-modified protein matrix is crosslinked with a bifunctional crosslinking reagent, and a method of making the same.

Abstract: Enzymatically cross-linked protein gels and methods for preparing them are disclosed. The methods comprise adding a transglutaminase, such as factor XIII, to a composition of a temperature-sensitive gel-forming protein, such as gelatin or collagen, and incubating the composition and transglutaminase under gel-forming conditions. The resulting gels have superior strength and thermal stability, and can be used within a variety of medical and industrial applications.

Abstract: A hydrophilic colloid is hardened with a vinyl-sulfone hardener in the presence of a borate compound in an amount sufficient to accelerate the rate of hardening. The borate compound is preferably a compound of Formula (I), or a salt, hydrate or precursor thereof:B(L).sub.n (I)wherein each L is independently --OH, --OR, --NH, --NR, or a substituted or unsubstituted alkyl group, substituted or unsubstituted aryl group, or substituted or unsubstituted heterocyclic group; R is a substituted or unsubstituted alkyl group or substituted or unsubstituted aryl group; and, n is 1, 2, or 3, with the proviso that at least one L is --OH. Preferred borate compounds are sodium and potassium borate, and hydrates thereof, and phenyl boronic acid.

Abstract: The invention features a method for the selection and expansion of bone marrow stromal cells. The method includes the steps of obtaining bone marrow stromal cells; introducing the stromal cells into a vessel pre-coated on an inner surface with a gelatin, and containing a culture medium including an acidic fibroblast growth factor ("aFGF") polypeptide; and expanding the stromal cells in the culture medium under conditions and for a time sufficient to obtain an increased number of bone marrow stromal cells. The culture medium additionally can include heparin, and the vessel additionally can be precoated with fetal bovine serum.

Abstract: An improved method of hardening a hydrophilic colloid is detailed. The hardening results in a stronger matrix and less water pickup. These and other advantages are obtained by hardening with a combination of at least one hardener chosen from Formula I either alone or in combination with at least one hardener chosen from Formula II: ##STR1## The substituents are defined.

Abstract: Photographic emulsions are quickly chilled to a homogeneous, particulate gel by injection of carbon dioxide coolant, while the emulsion is agitated. This process is carried out in a housing having a pair of parallel auger screws to transport emulsion circuitously within the housing. Carbon dioxide coolant is injected through a plurality of nozzles in the housing and is then removed from the housing through a vent line.

Abstract: Mammalian granulocyte-colony stimulating factor (G-CSF) receptor proteins, DNAs and expression vectors encoding mammalian G-CSF receptors, and processes for producing mammalian G-CSF receptors as products of recombinant cell culture, are disclosed.

Abstract: The present invention relates to a gelatinase A inhibitor comprising as an active ingredient a peptide analogue consisting of an active minimum unit of gelatinase A inhibition obtained from APP (.beta.-amyloid precursor) or a peptide analogue comprising it. Gelatinase A can be qualified and quantified using any of the gelatinase A inhibitors according to the present invention.

Abstract: A modified gelatin is disclosed wherein part of the free carboxyl groups is replaced by modifiers having more acid end-standing groups chosen from --SO.sub.3 M, --OSO.sub.3 M, --SSO.sub.3 M, ---OPO(OH).sub.2, --OPO(OH)(OR.sup.2), --PO(OH).sub.2, --PO(OH)(OR.sup.2).In a preferred embodiment such a modified gelatin is incorporated in a DTR photographic material which after processing can serve as a lithographic printing plate. Thanks to the more hydrophilic character of the modified gelatin the differentiation between printing and non-printing areas is improved and toning at printing start-up is reduced.

Abstract: A process for the preparation of spherules and emulsions containing such spherules. A primary oil-in-water emulsion is formed containing particles comprising one or more active principles in oily form suspended in water, the water optionally containing at least one protein. Controlled division of the primary emulsion is achieved by combining the primary emulsion with a water-immiscible solvent to create a second emulsion containing spherules of the primary emulsion. Preferably, the particles of the primary emulsion have mean diameters of about 1 .mu.m, and preferably, the spherules contained in the second emulsion have a diameter ranging from 100 .mu.m to 500 .mu.m. If protein is contained in the primary emulsion, the protein can be cross-linked. Further, the spherules can be separated from the water-immiscible solvent.

Abstract: A method for forming a controlled release polymeric substrate is provided by contacting a polymeric substrate with a liquid mixture containing a cross-linking agent at least partially soluble therein comprising water and an organic liquid, for a period of time and at a temperature and concentration of the agent sufficient for the agent to penetrate the substrate to form cross-linking bridges in the substrate in a decreasing concentration gradient beneath the surface.

Abstract: Gelatin, having high Bloom or gel strength in excess of 300, is extracted from fish, with high yield, by pre-treating collagen rich fish skins with a limewater (Ca(OH).sub.2) solution suspension with a concentration of between 19 gm of Ca(OH).sub.2 /liter of water/kg of tilapia fish skin to 100 gm Ca(OH).sub.2 /liter of water/kg of fish skin for a period of time between ten to sixty days and optimally between two to four weeks. For fish with higher percentage of fat content, a minimum concentration is at least 50 gm of Ca(OH).sub.2 /liter of water/kg of fish skin to avoid putrefaction. For fish with easily extractable gelatin, such as Nile perch, soaking time is from 3 to 10 days with a concentration of Ca(OH).sub.2 /liter of water of about 15 gm. At concentrations above 100 gm of Ca(OH).sub.2 /liter of water/kg of fish skin and/or treatment time periods in excess of four weeks, Bloom strength dramatically decreases.

Abstract: A modified gelatin is disclosed wherein part of the free carboxyl groups is replaced by modifiers having more acid end-standing groups chosen from --SO.sub.3 M, --OSO.sub.3 M, --SSO.sub.3 M, --OPO(OH).sub.2, --OPO(OH)(OR.sup.2), --PO(OH).sub.2, --PO(OH)(OR.sup.2).In a preferred embodiment such a modified gelatin is incorporated in a DTR photographic material which after processing can serve as a lithographic printing plate. Thanks to the more hydrophilic character of the modified gelatin the differentiation between printing and non-printing areas is improved and toning at printing start-up is reduced.

Abstract: A process for the preparation of gelatin from powdered bone, which consists in subjecting the powdered bone to a first treatment with an acid solution at a temperature below ambient temperature in order to solubilize the phosphates, and then to a second treatment with an acid solution at a temperature of between 60.degree. C. and 85.degree. C. in order to isolate a broth from which the gelatin is extracted. Type A gelatin with a gel strength of more than 300 blooms and a gelling time of less than 100 seconds.

Abstract: A method for modulating the specific activitiy of a target protein which is being purified. A controller protein is added to the target protein prior to conducting a final purification step in a purification process.

Abstract: Novel compounds represented by formula (I) ##STR1## wherein R.sub.1 and R.sub.2 represent hydrogen or alkyl, R.sub.3 represents hydrogen, alkyl, substituted alkyl or CONR.sub.1 R.sub.2, and n is 0 to 6, can be used to harden gelatin. The compounds are particularly useful for hardening gelatin of a photographic element.

Abstract: The method for preparing high grade gelatin with a specific methionine content and with reduced methionine variability from batch to batch and within a single extraction includes controlling the amount of and variability of oxidant present during processing of bone stock into gelatin. Such controls include control of oxidant concentration and range in process water, control of volume of process water used in gelatin-making process and restriction of the range of gelatin extracts used in the product gelatin. Once the aim level of oxidant has been set, the total range of oxidant around the set point should be less than 220 meq per 100 kg dry bone.

Abstract: An inexpensive, ballasted optical brightener for use in photographic elements is prepared by reacting an optical brightener of the formula ##STR1## where M is a cation; X is a group capable of undergoing nucleophilic displacement; and Z is ##STR2## or --O--R.sub.3, where each of R1 and R2 is a hydrogen atom, or an aromatic group which can be unsubstituted or substituted with one or more groups unreactive towards X; and R3 is an aromatic group which can be unsubstituted or substituted with one or more groups unreactive towards Xwith a water soluble polymer, such as gelatin. The resulting ballasted optical brightener is stable in aqueous photographic compositions.

Abstract: A photographic element comprising a modified gelatin whereby the modification results in carbamoyl groups by forming peptide bonds using fast-acting hardener. The derivatization involves initial reaction with a carboxyl activator followed by addition of a substituted amine thereby forming an amide linkage on the polypeptide chain. The resulting gelatin and photographic elements comprising such gelatin have a decreased propensity for water absorption without the loss of sensitometric properties.

Abstract: A aqueous stock solution for preserving human cells, particularly leukocytes, which includes 20-40% modified gelatin by weight in a physiologically acceptable buffer at pH4-7.5.

Abstract: Hydrophilic organic colloids such as collagen or gelatin are modified for use in photographic elements such as film or paper, or for use as reagents in automated dry chemical analyzers. The modification comprises reaction of some of the carboxy groups attached to the polypeptide with (i) a amide bond forming agent, e.g. 1-pyrrolidinylcarbonylpyridinium chloride, and (ii) a di- or triamine, such as piperazine, diethylenetriamine or ethylenediamine. Such modification enables that colloid to react faster with a gelatin hardener such as bis(vinylsulfonyl)methane (BVSM). When coated over an equal amount of unmodified gelatin, and both layers imbibed with BVSM, a modified gelatin layer showed an enzyme resistance greater than that of the unmodified gelatin. This demonstrates that the modified gelatin hardened preferentially.

Abstract: A crosslinked product of a primary amino group-containing compound such as proteins, chitosan or a mixture thereof is disclosed. The product has a crosslinked structure formed by crosslinking with an iridoid compound, and the blue color developed by the crosslinking is decolorized. Also, a method for decolorization of the above crosslinked product is disclosed. The method comprises reacting a crosslinked product obtained by crosslinking a primary amino group-containing compound with an iridoid compound, with at least one decolorizing agent selected from the group consisting of an oxidizing agent, a reducing agent and a reductone. The decolorized product and the method for decolorization according to the present invention can be broadly applied in the fields of foodstuffs, cosmetics, pharmaceuticals and the like where blue tone coloration is undesirable.

Abstract: Methods and compositions are provided for the treatment and repair of defects in the cartilage or bone of humans and other animals as in full-thickness defects in joints. The defect in bone is filled with a matrix having pores large enough to allow cells to populate the matrix and to form blood vessels. The matrix filling the bone defect contains an angiogenic factor and also contains an osteogenic factor in an appropriate delivery system. To induce cartilage formation, a defect in cartilage is filled with a matrix having pores sufficiently large to allow cartilage repair cells to populate the matrix. The matrix filling the defect in cartilage contains a proliferation agent and also contains a transforming factor in an appropriate delivery system. The matrix may also contain a chemotactic agent to attract cartilage repair cells.

Abstract: Proteins which specifically inhibit coagulation Factor Xa. The inhibitors, which do not inhibit Factor VIIa, kallikrein, trypsin, chymotrypsin, thrombin, urokinase, tissue plasminogen activator, plasmin, elastase, Factor XIa or S. aureus V8 protease, are polypeptides of 60 amino acid residues. The inhibitors may be purified from Ornithodoros moubata extract, synthesized, or produced using a recombinant DNA yeast expression system.

Abstract: A method for hardening gelatin which comprises using as a hardening agent a compound represented by formula (I): ##STR1## wherein R.sub.1, when taken along, may be alkyl of 1 to 20 carbon atoms, aralkyl of from 7 to 20 carbon atoms, aryl of from 6 to 20 carbon atoms, and alkenyl of from 2 to 20 carbon atoms. R.sub.1 and R.sub.2 can also combine with each other to form a heterocyclic ring of 5 to 8 atoms. The R.sub.1 -R.sub.2 ring contains the nitrogen atoms to which R.sub.1 and R.sub.2 are attached, and may also contain an additional nitrogen atom. R.sub.2 and R.sub.3 can combine to form either a 5 or 6 membered ring. The R.sub.2 -R.sub.3 ring contains the nitrogen atom to which R.sub.2 is attached, and may also contain one or two additional nitrogen atoms. R.sub.4 may be hydrogen or alkyl of 1 to 4 carbon atoms. R.sub.

Abstract: Fine particles of gelatin and amino acid used in the present invention are particularly suitable for use in combination with resins.Gelatin particles used in the present invention have the number-average molecular weight of 8,500 or less, and amino acid particles with the number-average molecular weight of 200 or less, so that efficient pulverization becomes possible and that gelatin and amino acid particles maintain their intrinsic properties as they are not subject to denaturation during pulverization. Resultant particles are neither too large nor too small but are uniform in size and are particularly suitable for use in combination with resins.

Abstract: Hydrophilic organic colloids such as collagen or gelatin are modified for use in photographic elements such as film or paper, or for use as reagents in automated dry chemical analyzers. The modification comprises reaction of some of the carboxy groups attached to the polypeptide with (i) a amide bond forming agent, e.g. 1-pyrrolidinylcarbonylpyridinium chloride, and (ii) a di- or triamine, such as piperazine, diethylenetriamine or ethylenediamine. Such modification enables that colloid to react faster with a gelatin hardener such as bis(vinylsulfonyl)methane (BVSM). When coated over an equal amount of unmodified gelatin, and both layers imbibed with BVSM, a modified gelatin layer showed an enzyme resistance greater than that of the unmodified gelatin. This demonstrates that the modified gelatin hardened preferentially.

Abstract: This invention relates to the production of oil-in-water emulsifiers and emulsion stabilizers. More particularly, this invention relates to methods for the production of novel hydrophobically modified proteins which may be used as emulsifiers or to stabilize emulsions.This invention also relates to products incorporating these hydrophobically modified protein emulsifiers and emulsion stabilizers. These compounds may be used in many applications such as paints, dyes and cosmetics.

Abstract: Methods and compositions are provided for the treatment and repair of defects or lesions in the cartilage of humans and other animals. The defect or lesion in the cartilage may be first treated with an enzyme to remove proteoglycans from the defect area. To induce cartilage formation, the defect is filled or otherwise dressed with a biodegradable matrix having pores sufficiently large to allow repair cells to populate the matrix. The matrix filling the defect contains a proliferation agent at a concentration sufficient to stimulate proliferation of repair cells and a transforming factor in an appropriate delivery system to release the transforming factor at a concentration sufficient to transform repair cells in the matrix and defect area into cartilage-producing chondrocytes. The matrix may also contain a chemotactic agent to attract repair cells. The entire treatment may be carried out in a single arthroscopic or open surgical procedure.

Abstract: At least part of the fat in fat-containing manufactured food products is replaced by gelatin in an amount by weight which is generally no more than 10% of the weight of the original fat content which has been replaced. Suitable gelatin for this purpose may be made from fish waste comprising fish skins by an aqueous extraction process, such as e.g. a stepwise process including separate alkaline, mineral acid and organic acid treatment steps. The gelatin is said to mimic the sensation experienced by the consumer of the creaminess or richness of foodstuffs containing regular fat levels. Exemplary products to which the invention may be applied are baked goods, dressings, whipped toppings, frostings, cream fillings and spreads. In Examples, the fat content is thus reduced substantially, to give food products which closely resemble in quality the higher fat-containing analogs.

Abstract: A soluble, chain extended gelatin having a high molecular weight and significantly higher viscosity at equivalent gelatin concentration compared to standard gelatin and significantly faster setting time is produced by preparing an aqueous gelatin composition containing from about 6% to about 18% dry weight of gelatin and from about 0.25 to about 5 millimoles of a bis-(vinyl sulfonyl) compound per 100 grams of gelatin, heating the composition at a temperature of from about 40 to about 60.degree.C. and at a pH of from about 4.5 to about 7 for from about one to about eight hours.

Abstract: A method of bonding collagen to synthetic polyester fibers, particularly DACRON. The method involves providing synthetic polyester fabric fibers having repeating carbonyl groups, hydrogenating the repeating carbonyl groups and then conducting a transesterification step which includes the addition of free amine groups. The free amine groups are reacted with a bifunctional crosslinking agent to produce modified polyester fibers. The final step involves adding collagen to the modified polyester fibers for a time sufficient to produce covalent bonding of the collagen to the fibers.The invention also involves the making of a fabric matrix comprised of synthetic polyester fibers, particularly DACRON, and collagen being covalently bound to the fibers. Such matrix can be utilized in ligament prosthesis design.

Abstract: A method of crosslinking protein comprises making a composition which comprises a protein, a sugar, a water-soluble salt of a carboxylic acid, water, and an additional ingredient which is to be encapsulated or entrapped within the crosslinked protein matrix. The composition is thereafter heated while maintaining the moisture content at a level of at least about 3 weight percent, based on the weight of the composition.A product comprises a protein which is crosslinked to degree at which it is substantially insoluble upon being placed in water at 100.degree. C. for at least 3 minutes, a sugar, a water-soluble salt of a carboxylic acid, water, and an additional ingredient which is encapsulated or entrapped within the crosslinked protein matrix.

Abstract: An artificial carrier for immobilization of biological proteins, which are composed of particles comprising gelatin, an alkali metal metaphosphate and an anionic high-molecular electrolyte, said particles being water-insolubilized by a treatment with an aldehyde.

Abstract: Method for oxidative folding of peptide and protein substrates to form disulfide bonds using dimethyl sulfoxide and other equivalent sulfoxides as mild oxidizing agents.

Abstract: A method for crosslinking protein comprises making an aqueous compositiion of a protein, sugar, a salt, and water, followed by heating the composition while maintaining the moisture content of the composition at a level of at least about 3 weight percent. The composition is made, and the heating carried out, so that the protein is crosslinked to a degree at which it is substantially water insoluble upon being placed in water at 100.degree. C. for at least 3 minutes. A crosslinked protein product comprises a protein crosslinked to a degree that it is substantially water insoluble upon being placed in water at 100.degree. C. for at least 3 minutes, a sugar, a salt, and water.