Abstract: The present invention relates to a method for producing porous polysaccharide beads, comprising: (a) mixing a water-based solution of a polysaccharide under stirring with an essentially water-immiscible first organic phase to form an emulsion which separates into two continuous phases; (b) adding a second organic phase comprising an emulsifier and an organic solvent to form a three-phase system; (c) allowing the three-phase system to emulsify; and (d) decreasing the temperature below the gelling point of the polysaccharide, thereby obtaining beads having two sets of pores, said method being characterised in that the emulsifier is a water-insoluble polymer capable of stabilizing said three-phase system.

Abstract: The invention relates to a method for the production of spherical microparticles consisting totally or partly of at least one water-insoluble polysaccharide, wherein the at least one water-insoluble polysaccharide is dissolved in a solvent or solvent mixture, the solution thus formed is introduced into a precipitating agent or precipitating agent mixture, the mixture obtained is optionally cooled and the formed microparticles are separated. The invention is characterized in that the water-insoluble polysaccharide is selected from a polyglucan containing branches with a degree of branching higher than zero and no higher than 8% and a mixture of a polyglucan containing branches and a linear polysaccharide, wherein the proportion of polyglucan containing branches in the mixture is at the most 30% by weight in relation to the overall weight of the polysaccharide and the polyglucan.

Abstract: Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.

Abstract: A method of producing biosynthetic copolymers comprising glucose and glucose analogs is provided. Glucose:glucose analog copolymers such as glucose:glucosamine, glucose:N-acetylglucosamine and glucose:glucosamine:N-acetylglucosamine are also provided.

Abstract: Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.

Abstract: The present invention relates to dextran whose boron content is reduced to a value less than 0.30 &mgr;g/g (dry basis) calculated on the basis of boron atom, a process for producing the same, and dextran with which a container is filled in a solution state. Dextran of the present invention is obtained by treating a boron-containing dextran with a lower alcohol, and said dextran has such a characteristic that deposition is inhibited or the deposition rate is drastically reduced when using it in the form of a solution. Therefore, an isotonic sodium chloride solution of said dextran is suitably used as substitute plasma or external perfusate in an operation.

Abstract: The present invention provides a metal charged iminodiacetic acid (IDA) cellulose for detecting a test sample having a histidine tag. The present invention also provides methods for determining cloned protein expression and function. Additionally, the present invention includes a method for the handling of denatured proteins with subsequent renaturation in situ (parenthetically after binding to metal charged IDA cellulose). A wide range of applications are contemplated for the metal charged IDA cellulose including two-dimensional high throughput screening of proteins.

Abstract: Disclosed is a platinum complex of formula (I) wherein X represents a halogen atom, B represent, independently to each other, a halogen atom, a hydroxyl group or a carboxylate group containing 1 to 6 carbon atoms, and A represents a croup —NH2—R wherein R is a tricyclic hydrocarbon moiety containing 10 to 14 carbon atoms which may be optionally substituted on the tricyclic ring by one or two alkyl group(s) each containing 1 to 4 carbon atoms, and, furthermore, an inclusion complex of the above platinum complex with beta- or gamma-cyclodextrin which may be optionally substituted by hydroxyalkyl groups containing 1 to 6 carbon atoms. There is also disclosed a process for the manufacture of the complex of formula (I) based on oxidation of a complex of divalent platinum of formula (II) with hydrogen peroxide and on optional substitution of hydroxyl groups in the obtained product with carboxylate groups by action of an acylating agent.

Abstract: The present invention is directed to particulate drug carriers, such as vesicles, formed from polysaccharide derivatives. A polysaccharide bearing at least one non-ionic hydrophilic group attached to an individual monosaccharide unit is hydrophobised to form a derivative bearing at least one long chain alkyl residue. Particle formation is then induced in the presence of cholesterol. The particles are suited for entrapment or conjugation of pharmaceutically active ingredients.

Abstract: Biodegradable hydrogels are formed by photocrosslinking dextran-maleic acid monoesters in which the average degree of substitution of each glucose unit of each &agr;-D-glucopyranosyl of dextran by maleic acid ranges from 0.60 to 1.6 and which have a weight average molecular weight ranging from 40,000 to 80,000 on a dextran basis. The hydrogels at pH 7 have maximum swelling ratios ranging from 500 to 1,500 percent. The hydrogels are characterized by increase in swelling ratio as average degree of substitution increases. The hydrogels are useful, for example, for drug delivery and solubility enhancers of drugs, as protective encapsulators of viruses used in gene therapy, and for conventional uses of hydrogels.

Abstract: Methods of promoting angiogenesis are provided which include administering to a suitable locus a cross-linked polysaccharide having a positive charge. Preferred cross-linked polysaccharides are biodegradable beads. A positive charge may be provided by diethylaminoethyl (DEAE) groups associated with the polysaccharide.

Abstract: Emulsifiers based on the reaction product of hydrocolloid and dicarboxylic anhydrides, especially useful in the preparation of oil-in-water emulsions.

Abstract: A drug complex characterized in that a residue of a drug compound such as antineoplastic agents and a carboxy(C1-4)alkyldextran polyalcohol obtained by treating a dextran under conditions that enable substantially complete polyalcoholization are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Said complex is characterized-in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.

Abstract: A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation.

Abstract: Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.

Abstract: In a process for the preparation of pentaacetyl-&bgr;-D-glucopyranose by reacting D-glucose with acetic anhydride in the presence of sodium acetate catalyst, the improvement is provided wherein 5-10 mols of acetic anhydride are used per mol of D-glucose and the reaction is performed in an organic solvent. Pentaacetyl-&bgr;-D-glucopyranose is useful as intermediates for the synthesis of raw materials for industrial chemicals, medicines, cosmetics and the like.

Abstract: An aqueous phase inhibitor for quenching free radical polymerization comprising a free radical quenching agent having a hydrophilic tail is disclosed, as well as a coating and related methods. In one embodiment, the free radical quenching agent can either be an N-hydroxylamine or an N-nitrosonamine, the hydrophilic tail can be a polyhydric alcohol tail and the inhibitor can be a concentrate in a liquid medium such as water, alcohol and mixture thereof.

Abstract: This invention relates to the use of polysaccharide such as dextran to improve mucus clearance. In the present invention, dextran has been shown to reduce viscoelasticity and increase mucus clearability of sputum of cystic fibrosis patients. Dextran also reduced viscoelasticity of healthy dog mucus. The present invention therefore may be used to improve mucus clearance in cystic fibrosis patients and treat other conditions associated with defect in airway mucus clearance including chronic bronchitis, bronchiectasis and bronchial asthma.

Abstract: The use of a gel produced by polymerization of a dextran derivative which exhibits groups that contain an alkene structure, for separating nucleic acid by electrophoresis.

Abstract: A carrier and a method for preparing it are provided for use in the delivery of therapeutic agents. A polysaccharide is reacted with an oxidizing agent to open sugar rings on the polysaccharide to form aldehyde groups. The aldehyde groups are reacted to form covalent oxime linkages with a second polysaccharide and each of the first and second polysaccharide is selected from the group consisting of hyaluronic acid, dextran, dextran sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate and alginate.

Abstract: An iron-dextran compound for parenteral treatment of iron-deficiency anemia comprises hydrogenated dextran having a weight average molecular weight (Mw) between 700 and 1,400 Daltons, preferably approximately 1,000 Daltons, a number average molecular weight (Mn) of 400 to 1,400 Daltons and wherein 90% by weight of the dextran has molecular weights less than 2,700 Daltons and the Mw of the 10% by weight fraction of the dextran having the highest molecular weights is below 3,200 Daltons, said hydrogenated dextran having been subjected to purification by membrane processes having a cut-off value between 340 and 800 Daltons, in stable association with ferric oxyhydroxide.

Abstract: A method for preparing a drug complex in which a polysaccharide derivative having carboxyl groups and a residue of a drug compound are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids, or a drug complex in which a polysaccharide derivative having carboxyl groups and a residue of a drug compound are bound to each other without the spacer, characterized in that an organic amine salt of the polysaccharide derivative having carboxyl groups is reacted with the drug compound or the spacer bound to the drug compound in a non-aqueous system. The reaction between the polysaccharide derivative having carboxyl groups and the drug compound bound with the spacer or the like can be carried out in high yields, and when a drug compound having a lactone ring is subjected to the reaction, side reactions can be reduced.

Abstract: A method of modifying the binding properties on a surface of a solid phase on which there are nucleophilic groups, which is characterized in that the surface is treated with a solution of an activated polysaccharide; a method of immobilizing a chemical compound to a solid phase on which there are immobilized activated polysaccharides, whereby the chemical compound is contacted with the surface of the solid phase the binding properties of which are modified by the method according to the invention; an article which is characterized in that to the surface thereof an activated polysaccharide is fixated, such as activated dextran or activated agarose, and use of this article for use in solid phase reactions, in solid phase assay, solid phase peptide synthesis, solid phase nucleotide synthesis, solid phase enzyme processing, and joining of biological surfaces.

Abstract: A food or cosmetic composition containing a dextran composition synthesized by a dextran sucrase enzyme produced by a strain of Leuconostoc mesenteroides ssp. crenzoris. The food or cosmetic composition is prepared by fermenting a food or cosmetic composition containing sucrose with the strain, or the strain is cultured in a culture medium containing sucrose and the dextran composition produced is incorporated into a food or cosmetic substance.

Abstract: A food or cosmetic composition containing active dextran sucrase enzymes which are produced by a strain of Leuconostoc mesenteroides ssp. cremoris and which synthesize dextran. In addition to culturing the strain in a food or cosmetic composition containing sucrose to obtain a composition containing the active enzymes, the strain may be cultured in a culture medium containing sucrose to obtain a culture product containing the active dextran sucrase enzymes which may be isolated from the culture product and incorporated into a food or cosmetic substance.

Abstract: The invention provides a method of inhibiting complement in a mammal comprising administering to the mammal an effective amount of a carrier having coupled thereto a plurality of dipeptides selected from the group consisting of tryptophan-tyrosine, tyrosine-tryptophan and tryptophan-tryptophan. The invention further provides a method of prolonging the survival of tissue transplanted into a mammal comprising administering to the mammal an effective amount of a carrier having coupled thereto a plurality of dipeptides selected from the group consisting of tryptophan-tyrosine, tyrosine-tryptophan and tryptophan-tryptophan. The invention also provides a method of treating an inflammatory response in a mammal comprising administering to the mammal an effective amount of a carrier having coupled thereto a plurality of dipeptides selected from the group consisting of tryptophan-tyrosine, tyrosine-tryptophan and tryptophan-tryptophan.

Abstract: The invention is directed to the preparation of magnetic and non-magnetic particles coated with a polyaldehyde dextran material and a process for making the same. The polyaldehyde dextran coated particles of the invention are suitable for use in immunological assays and exhibit a reduced matrix effect in such assays when compared to convention particles without a polyaldehyde dextran coating.

Abstract: A polysaccharide conjugate comprises a polysaccharide with an attached entity having a molecular weight of at least 5000, the polysaccharide conjugate being capable of binding to cellulose. Preferred polysaccharides include tamarind seed xyloglucan, locust bean gum and enzyme modified guar. The attached entity is suitably a protein such as an enzyme, antibody or antibody fragment, or a particle possibly having a benefit agent such as a fragrance associated therewith. Because the polysaccharide conjugate binds to cellulose, which is present in cotton and other fabrics, paper, etc., binding of the conjugate to cellulose brings the attached entity into close proximity to a surface of or containing cellulose. The invention thus enables targeting of attached entities to such surfaces. The invention also provides a product incorporating the polysaccharide conjugate of the invention. The product is conveniently a laundry product such as a fabric washing product, e.g.

Abstract: There is provided a method of treating a human subject to prevent leakage of serum proteins from capillary endothelial junctions during a period of increased capillary permeability. The method comprises administering to a subject an effective amount of a composition containing hydroxyethyl starch, dextran or hydroxyethyl starch and dextran. The compositions contain these macromolecules in a molecular size and concentration to effectively seal the capillary junctions and stabilize the capillary membranes. The sealant effect is accomplished by a biophysical process due to the adhesiveness and configuration of the macromolecules, and because of their size. There is also provided a means of treating viral and other bacterial infections and cancer, by introducing into the composition of polysaccharide(s) a biological agent, preferably interleukin-2.

Abstract: An adsorbent for use in direct hemoperfusion to adsorb and remove harmful substances from blood is prepared by immobilizing a sulfated polysaccharide and/or its salt on a water-insoluble carrier. Preferably, the sulfated polysaccharide has a limiting viscosity of 0.005 to 0.5 dl/g and a sulfur content of 5 to 22% by weight, and is immobilized on the carrier in an amount of 0.02 to 200 mg per ml of carrier. Carrier particles can have an average particle size of 30 to 5000 .mu.m, and preferably 120 to 800 .mu.m. The sulfated polysaccharide inhibits adhesion of hemocytes and exhibits an anticoagulation property to extend blood coagulation time, and has additional functions of adsorbing releasing factors released from hemocytes, adsorbing lipoproteins, and enabling reduction of carrier particle size to about 30 .mu.m. Immobilizing a ligand on the carrier with the sulfated polysaccharide makes it possible to adsorb and remove specific substances in blood that bind to the ligand.

Abstract: New glucose-based surfactants and methods of their synthesis are described. The surfactants are synthesized through the preparation of an intermediate glucose 4,6-cyclic sulfate. The surfactants are economical to prepare and have excellent surface-active properties.

Abstract: Novel polysaccharide compounds are disclosed for decorating biomolecular surfaces to increase isotropic size and mask antigenicity. The oligosaccharides may be synthesized as repeating disaccharide units, or may be derived by acid hydrolysis of naturally occurring polysaccharides. Such natural sources include chondroitins obtained from shark cartilage, or hyaluronic acid. The polyanionic sulfate groups contained in the sugar moieties impart negative charges which repel the molecules from the negatively charged wall of capillaries, to lengthen retention times of decorated drug molecules, such as crosslinked hemoglobin, in the peripheral circulation.

Abstract: Strains of Leuconostoc mesenteroides ssp. cremoris which provide, upon culturing, dextran, and the strains include deposited strains CNCM I-1692 and CNCM I-1693.

Abstract: Novel methods are described to synthesize chromatography media. The methods describe a crosslinking procedure utilizing the catalytic effect of MnO(OH).sub.2 in obtaining a very rigid matrix. The mechanism of crosslinking is likely of free-radical type. This is also suggested by the concurrent functionalization steps which are known to be of free-mechanism and are greatly enhanced by MnO(OH).sub.2. The methods are simple and efficient as crosslinking and functionalization of the matrix takes place in the same step. High protein binding capacities are obtained along with an increased efficiency of the matrix. One particularly preferred process according to the present invention comprises: (1) reacting a polymeric carbohydrate matrix with an activating reagent which contains a halogen atom or epoxide and a double bond under alkaline conditions to generate an activated matrix; (2) reacting the activated matrix having double bonds inserted with a reagent or reagents producing MnO(OH).sub.

Abstract: The invention relates to a process for the preparation of polysaccharide-N-arylcarbamates in suitable form as supports for chromatography, which process comprises adding to polysaccharide carbamates, which may be substituted in the aryl moiety, an N-aryl-1-lower-alkylcarbamate-containing solution of an organic solvent, with vigorous stirring, until the polysaccharide derivative is completely dissolved and then adding thereto an aqueous solution containing a high molecular weight surfactant and, with continued stirring, removing the organic solvent from the emulsion so obtained and isolating the solid particles and washing and drying them. The polysaccharide derivatives so obtained can be used as support materials for the chromatographic separation of enantiomers.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.

Abstract: This disclosure describes pharmaceutical compositions and a method for treatment of joint inflammation and pain bought about by e.g. arthritis, physical trauma, bacterial or viral infection. In one embodiment, the method comprises administration of a bimodal molecular weight dextran formulation comprising 0.2 to 32% w/v of a dextran fraction with average molecular weight between 30,000 and 110,000 daltons and 0.2 to 6% dextran with an average molecular weight between 500 and 3,000 daltons, into the joint of a warm blooded animal.

Abstract: Small pore silicas serving as the inert core support in chiral stationary phases show a surprising increase in column capacity relative to conventional chiral stationary phases having large pore silicas as the inert core support. This affords increased productivity and lower overall costs for chiral resolutions using a chiral stationary phase as adsorbent and an achiral liquid as eluant.

Abstract: Iodized polymers, comprising a skeleton consisting of a dextrane onto which are grafted groups of the formula (I). Application of the these compounds as contrast products.

Abstract: A method of preparing a tresyl-activated dextran is disclosed in which an aqueous solution of dissolved dextran is reacted with a tresylating agent in a hexamethylphosphoric triamide and/or N-methyl pyrrolidinone solvent, and the formed tresyl-activated dextran is recovered. A method of immobilizing a chemical compound to the surface of a solid phase having nucleophilic groups covalently bound or non-covalently bound is also disclosed, the method involving treating the surface with a solution of tresyl-activated dextran prepared as described above, and contacting the chemical compound with the treated surface. An article is also disclosed wherein tresy-activated dextran prepared as described above is fixed covalently to its surface.

Abstract: Phosphorylated saccharide of the present invention includes at least one phosphate group in its molecule, selected from the group consisting of glucan, mannan, dextran, agar, cyclodextrin, fucoidan, gellan gum, Locust bean gum, guar gum, tamarind gum, and xanthan gum.

Abstract: The invention relates to methods of reducing Schiff bases and making chelator conjugates by treating with borane-pyridine complex.

Abstract: A method for production of toxin-binding, non-toxic, modified, biopolymers and the use thereof for the treatment of septic shock, infections and toxic states and to the use of them as carriers for transportation of biologically or therapeutically important materials (enzymes or drugs) into phagocytes or cells bearing Fc and complement receptors and as a natural source of energy for cells. The toxin binding, non-toxic structurally modified biopolymers are prepared by the reaction of polysaccharides containing alpha 1,4 or 1,6 linkages with glucose-1-phosphate catalyzed by glycogen phosphorylase enzyme in a buffer solution at pH 6.8-7.4 at a temperature of 20.degree.-30.degree. C. and by the separation of the obtained biopolymers in a well-known manner.

Abstract: Disclosed are methods for the preparation of resins comprising a support matrix having ligands capable of binding a target compound covalently attached thereto through a linking group comprising sulfide, sulfoxide, or sulfone functionality. Specifically, in the disclosed methods, a support matrix comprising ethylenically unsaturated functionality is converted to sulfide linkage by contact with a thiol group under free radical reaction conditions and subsequent optional oxidation of the sulfide to the sulfone or sulfoxide functionality.

Abstract: This invention describes bifunctional polysaccharides conjugated to both a chelating group suitable for the selective complexation of metal cations, and a targeting peptide specific for a cellular substructure. These bifunctional polysaccharides are primarily useful for the regulation, detection and quantification of metal ion levels, such as Ca.sup.2+, Mg.sup.2+, Na.sup.+, K.sup.+, or Li.sup.+, in specific cellular structures. Localization within the cellular structure is accomplished by the targeting peptide, whereupon the large, water-soluble polysaccharide prevents diffusion of the chelating group from the targeted site. When the target cell structure is the nucleus of a fertilized egg cell, the polysaccharide-chelator conjugate remains sequestered within the nucleus until the breakdown of the nuclear envelope, whereupon the reagent becomes sequestered into both daughter nuclei. This means of tracking daughter cells is practical even through several cell divisions.

Abstract: A process for the crystallization of an iron-dextran complex in readily-filterable form comprising adding slowly, with stirring, an acidified aqueous iron-dextran solution to a vessel containing a water miscible organic solvent such as methanol, as well as crystalline iron-dextran complexes so prepared.

Abstract: Disclosed are specifically designed binding, "protein imaged" sorbents which reversibly bind with high specificity and affinity a preselected macromolecule, specifically a protein. The sorbents define one or more cavities which have a binding surface complementary in shape to the molecular surface of the macromolecule and a plurality of positively and negatively charged chemical moieties spatially distributed in a mirror image and charge inverse of a subset of the ionizable groups on the molecular surface of the macromolecule. Also disclosed are methods of producing such sorbents, useful over a range of conditions, for both preparative and analytical chromatographic separations or for use in various types of analyses.

Abstract: The invention relates to a water-soluble, haemolytically inactive dextran fatty carboxylate with amphiphilic properties made from a dextran with an average molecular weight of 5,000 to 100,000 and a C.sub.10 to C.sub.14 fatty acid, preferably a C.sub.12 fatty acid, wherein the average degree of substitution is between 0.005 and 0.15 and is adjusted, depending on the average molecular weight of the dextran fatty carboxylate and the chain-length of the fatty acid used, in such a way that the dextran fatty carboxylate is soluble in water at room temperature, a process for its preparation and pharmaceutical or cosmetic preparations which contain it as solubilizer.

Abstract: Dextran esters with a molecular weight of 10,000-10,000,000 and ester side chains which are derived from acids with 6-18 carbon atoms, where the degree of esterification is adjusted, depending on the number of carbon atoms in the side chains and the molecular weight, to a value of 0.04-1.1 so that the dextran esters are insoluble in water at room temperature and are broken down by colonic bacteria, and their use for coating and/or embedding pharmaceutical active ingredients or drug formulations.

Abstract: Porous material of a polysaccharide and a method for preparations of such a material, wherein a water-based solution of the polysaccharide is mixed, with controlled stirring, with an essentially water-immiscible organic phase to form an emulsion, which when allowed to solidify, just before or during the gelling process, forms a network of two continuous phases, an aqueous polysaccharide phase and a flow-pore-forming organic phase, resulting in a material with two types of pores: small diameter diffusion pores and large diameter flow through pores.