Abstract: A method for analysing heparins or low-molecular-weight heparins, characterized in that the sample to be assayed is depolymerized by the action of heparinases and then, where appropriate, the depolymerizate obtained is reduced and then an analysis is carried out by high performance liquid chromatography.

Abstract: The present invention relates to a method and apparatus for isolating anticoagulant heparin or heparan sulfate by binding the anticoagulant heparin or anticoagulant heparan sulfate onto an affinity matrix and separating the non-bound material from the bound material. The affinity matrix is made of a fibroblast growth factor immobilized on a support. The invention also relates to a method and composition for neutralizing anticoagulation catalyzed by heparin, a heparin mimic, or a heparin derivative, by contacting heparin, a heparin mimic, or a heparin derivative with a fibroblast growth factor.

Abstract: A method of increasing proliferation of cells which comprises adding to cells a cellular proliferating amount of a primary hydroxyl group of N-acetylglucosamine selectively desulfated heparin having the following characteristics for an enzyme digestion product of the heparin: (1) contents of unsaturated disaccharides of the following formulae (a) and (b): measured by high performance liquid chromatography in the enzyme digestion product of the selectively desulfated heparin are less than 40% and 30 to 67%, respectively, (2) a content of disaccharides containing an N-substituted sulfate group is 75 to 95%, and (3) the weight average molecular weight Mw is 4,000 to 30,000 dalton.

Abstract: A biologically active conjugate is disclosed comprising a biopolymer and a therapeutic agent joined by a disulfide bond. The conjugate, when formulated in a pharmaceutical composition with a suitable carrier, has improved in vivo stability and activity, and can be targeted to a variety of cells, tissues and organs.

Abstract: The invention relates to a process for the depolymerization of glycosaminoglycanes characterized by the use of high-energy radiation in the presence of an organic compound selected from the group consisting of ethers, alcohols, aldehydes, amides and formic acid. The invention also relates to intermediate depolymerized heparin having Mw comprised between 1,000 and 5,500, absorbance at 400 nm below 0.300 and ratio S03−/COO− equal to or higher than in the starting heparin. The intermediate depolymerized heparin can be dissolved in a buffer solution and fractionated by Gel Permeation for obtaining the desired Molecular Weight.

Abstract: The present invention provides a new method to process a solution containing heparin; heparin salts or heparin complexes in a solvent or a mixture of solvents to a solid form of heparin products characterized by use of a drum dryer at atmospheric pressure or under vacuum and at a suitable drying temperature.

Abstract: The present invention relates to mixtures of polysaccharides derived from heparin having a mean molecular weight of 1500 to 3000 Daltons and an anti-Xa/anti-IIa ratio greater than 30, their method of preparation and pharmaceutical compositions containing them.

Abstract: The present invention provides anticoagulant piscine gill glucosaminoglycans, high affinity anticoagulant piscine glycosaminoglycans anticoagulant glycosaminoglycans extractable from salmon guts, skin, tail or gills and salts and derivatives thereof.

Abstract: A product having application in the medical, pharmaceutical and dermo-cosmetic fields comprising a cross-linked polysaccharide in which cross-linkage exists only through amide bonds between carboxy groups of the polysaccharide and amino groupss of a polyamine.

Abstract: The present invention relates to newly identified polynucleotides, and polypeptides encoded by such polynucleotides, the use of such polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, a polypeptide of the present invention is a heparanase-related endoglucuronidase. The invention also relates to vectors and host cells comprising a polynucleotide of the invention. Furthermore, the invention relates to antibodies directed to polypeptides according to the present invention and to pharmaceutical compositions and diagnostic reagents comprising such antibodies, polypeptides or polynucleotides. The invention further relates to a method of altering, modifying or otherwise modulating the level of expression of the heparanase-related endoglucuronidase in a cell or in a organism. A further aspect of the invention are assay systems suitable for identifying modulators, e.g. agonists or antagonists of such polypeptides.

Abstract: New process for the preparation of chondroitin sulfates from the bacterial origin polysaccharide named K4, by defructosilation followed by selective sulfation.

Abstract: A polynucleotide (hpa) encoding a polypeptide having heparanase activity, vectors including same, genetically modified cells expressing heparanase, a recombinant protein having heparanase activity and antisense oligonucleotides and constructs for modulating heparanase expression.

Abstract: Nucleotide sequences comprising regulatory regions of the human heparanase gene are provided. Also provided are methods and compositions for regulating heparanase expression, as well as methods and compositions for using heparanase sequences to regulate a heterologous target gene.

Abstract: An article of metal, glass, ceramics or plastics having a surface for contact with tissue or with circulating blood, has a surface coating of an organopolysiloxane and heparin, in which coating the organopolysiloxane is adherent to the surface of the article and has cationic groups that form ionic bonds with anionic groups of the heparin. The surface for contact with circulating blood may be an interior surface of a cannula or tubing or of a blood oxygenator or it may be a working surface of a blood filter. The polymer may be poly-[dimethylsiloxane-co-methyl-(3-hydroxypropyl)siloxane]-graft-poly(ethylene glycol) [3-(trimethylammonio) propyl chloride] ether.

Abstract: A pharmaceutical composition for the regulation of cytokine activity in a subject. The composition features an effective amount of an oligosaccharide to inhibit the cytokine activity, preferably through inhibition of TNF-alpha activity. The oligosaccharide is more preferably up to four saccharide units in length, and optionally and more preferably, is N-sulfated with at least one other sulfur moeity. The compositions are useful for the treatment of various pathological conditions related to, caused by or promoted through, cytokine activity.

Abstract: The invention provides vitamin K-dependent polypeptides with enhanced membrane binding affinity. These polypeptides can be used to modulate clot formation in mammals. Methods of modulating clot formation in mammals are also described.

Abstract: A process for the preparation of cross-linked polysaccharides containg carboxy groups. The process comprises a first step of activating the carboxy groups in an anhydrous aprotic solvent and then reacting with a polyamine. The cross-linked polysaccharide may be subjected to sulfonation of the five hydroxy groups.

Abstract: Disclosed are methods of conjugating biologically active substances, particularly, alpha-interferon, with a hyaluronan or a mixture of a hyaluronan with at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone. Also disclosed are stable intermediates formed by partially reacting a hyaluronan with divinyl sulfone and stopping the reaction before completion to leave free, or reactive vinyl groups on the hyaluronan molecule available for conjugation with the biologically active substance.

Abstract: A glycosaminoglycan 6-O-sulfotransferase having an activity of transferring sulfate to a hydroxyl at position 6 of a glycosamine residue of a glycosaminoglycan, which has a ratio of relative activities to substrates satisfying completely desulfated N-acetylated (CDSNAc) heparin/completely desulfated N-resulfated (CDSNS) heparin≧0.05 and a molecular weight as calculated from constituent amino acids of from 53,000 to 58,000 daltons.

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: The invention relates to novel disaccharides of formula (I), wherein R1 is selected from the group consisting of hydrogen, linear or branched (C1-C4) alkyl, phenylalkyl with less than ten carbon atoms and —COCH3; R2 is selected from the group consisting of hydrogen, —COCH3 and SO3M; R3 is selected from the group consisting of hydrogen, linear or branched (C1-C4) alkyl, phenylalkyl with less than ten carbon atoms, —COCH3 and y —COPh, Ph being phenyl; G is selected from amongst —COOR4 and —COOM, R4 is selected from the group consisting of hydrogen, (C1-C2)-alkyl and arylalkyl with less than sixteen carbon atom; A is selected from the group consisting of hydrogen, —SO3H, —SO3M and —COCH3; B is selected from the group consisting of hydrogen, —SO3H, —SO3M and —COCH3, wherein either A or B are necessarily either —SO3H or —SO3M, M being a an organic or metallic cation.

Abstract: Heparin-polyoxyalkylenepolyamine adducts, and methods of making and using such adducts are disclosed. Compositions including a quaternary ammonium heparin complex, a moisture curable polysiloxane, and an organic solvent are also disclosed, along with methods of making and using such compositions.

Abstract: The present invention relates generally to sulfated oligosaccharides, and in particular to the use of certain sulfated oligosaccharides as agents for lowering blood levels of triglycerides such as, for example in treatment of hypertriglyceridaemia.

Abstract: The description relates to a process for the production of esters of heparin, wherein from 0.1 to 2 g of a halogenated reagent having the formula R—CH2—X, where R is a phenyl group which is non-substituted or substituted by a halogen atom or by a nitro group, and X is a halogen atom, preferably chlorine, are reacted with from 2 to 20 g of one of the quaternary ammonium salts of heparin in from 30 to 250 ml of N,N-dimethylformamide and/or N,N-dimethylacetamide.

Abstract: Polysaccharides, which are widely used as an anticoagulation drugs, especially heparin, are clinically administered only by intravenous or subcutaneous injection because of their strong hydrophilicity and high negative charge. Amphiphilic heparin derivatives were synthesized by conjugation to bile acids, sterols, and alkanoic acids, respectively. These heparin derivatives were slightly hydrophobic, exhibited good solubility in water, and have high anticoagulation activity. These slightly hydrophobic heparin derivatives are efficiently absorbed in the gastrointestinal tract and can be used in oral dosage forms. Methods of using these amphiphilic heparin derivatives and similarly modified macromolecules for oral administration are also disclosed.

Abstract: The instant invention provides methods for identifying agents that modulate an enzymatic activity of a carbohydrate sulfotransferase. The methods generally involve contacting the sulfotransferase, in a reaction solution, with a sulfate donor, a test agent, and a polymeric sulfate acceptor that is readily separated from the reaction solution. Determination of an effect of the test agent on the sulfotransferase is by detecting the amount of sulfate in the polymeric sulfate acceptor that has been separated from the reaction solution. The invention further provides kits for use in carrying out the subject methods.

Abstract: The present invention is related to heparin-like compounds characterized by their capacity of inhibiting collagen-induced platelet aggregation in flowing whole blood and their use for prophylactic treatment of arterial thrombosis associated with vascular or microvascular injury and interventions. Said properties are related to a high coupling density of negatively charged heparin or heparin-like glycosaminoglycan molecules, present in multiple heparin or heparin-like glycosaminoglycans as well as in proteoglycans containing said multiple heparin or heparin-like glycosaminoglycans or lower-molecular-weight heparin or heparin-like glycosaminoglycans connected directly or through spacer/linker molecules to globular core molecules. Heparin-like compounds, with said properties are obtainable from mammalian mast cells, by tissue extraction or cell cultivation.

Abstract: The present invention provides an anti-thrombogenic and cellular-adhesion coating composition for blood-contacting surfaces. The coating comprises a covalent complex of from 1 to 30 hydrophobic silyl moieties of Formula I: wherein R1 is an C1-18 alkyl or C6-32 aryl group, each R2 is independently selected from the group consisting of C1-18 alkyl and C6-32 aryl, R3 is N or O, n is a number from 1 to 10, directly bound to a heparin molecule via covalent bonding, with an adhesive molecule directly bound to the heparin molecule. In one embodiment, the coating comprises benzyl-(1,2 dimethyl)disilyl heparin, wherein an adhesive molecule, such as fibronectin, is bound to the heparin.

Abstract: Heparin-polyoxyalkylenepolyamine adducts, and methods of making and using such adducts are disclosed. Compositions including a quaternary ammonium heparin complex, a moisture curable polysiloxane, and an organic solvent are also disclosed, along with methods of making and using such compositions.

Abstract: The present invention provides a new class of compounds presenting a high compatibility with tissues and organic fluids. Such new compounds are polysaccharides essentially formed of units of uronic acid and/or hexosamine, containing nitro groups —ONO2 covalently bonded to the saccharide structure. Preferably, the polysaccharides according to the invention are prevalently formed of disaccharide repeating units formed of uronic acid and hexosamine. These compounds, in psychological conditions, selectively release NO, allowing a reduction in the amount of NO needed to achieve a determined therapeutical effect. This result has been achieved by functionalizing polyssacchrides essentially formed of units of uronic acid and/or hexosamine, with subsituents containing a ONO2? group.

Abstract: The present invention relates to oligosaccharides of formula: to mixtures thereof, to diastereoisomers thereof, to a process for preparing them, to pharmaceutical compositions containing them, and to their use in preventing or treating a disease associated with an inflammatory process involving the production of nitric oxide.

Abstract: The present invention relates to chemical complexes consisting of cysteine or derivatives of cysteine and an aminosugar as well as pharmaceutical compositions and dietary supplements comprising such complexes. The invention further relates to the use of such compositions or complexes for the preparation of a medicament or a dietary supplement in the suppression of hypersensitivity and inflammatory reactions such as rheumatic or dermatological disorders or to a method of treating such diseases by administering such compositions and complexes.

Abstract: The bioactivity of TNF is inhibited by administering heparin or a derivative thereof along with a soluble TNF receptor. The heparin or derivative thereof can be administered simultaneously with the soluble TNF receptor, either in separate compositions or in compositions containing both heparin or a derivative thereof and at least one soluble TNF receptor. The heparin or derivative may also be administered without the soluble TNF receptor and still effect some amount of inhibition of TNF bioactivity.

Abstract: The present invention relates to pharmaceutical compositions containing as an active ingredient at least one oligosaccharide of formula: to novel oligosaccharides of formula (I), to mixtures thereof and to methods for their preparation.

Abstract: This invention relates to a process for producing a desulfated polysaccharide, which comprises reacting a sulfated polysaccharide having a saccharide in which a primary hydroxyl group is sulfated, as a constituent sugar, with a silylating agent represented by the following formula (I) 1

Abstract: A nucleic acid coating composition including a polyanion bound, directly or through one or more intermediates, to a medical device surface, with a condensate comprising a polycation and nucleic acid bound to the polyanion, devices incorporating such coating compositions, and methods for making. In one embodiment, a silyl-heparin complex is provided, bound to a medical device surface by hydrophobic interaction with the silyl moiety, with a polycation and nucleic acid condensate bound to the heparin by electrostatic interaction.

Abstract: The invention relates to a novel heparin having an average molecular weight within a range of from 10 to 11.5 kd, in particular, an average molecular weight of 10 kd. Said heparin is obtained by controlled depolymerization of unfractionated heparin and subsequent molecular filtration. Said heparin is used for the preparation of a medicament for the prophylaxis and therapy of thrombo-embolic processes and, inter alia, for the inhibition of coagulation in extracorporeal circulations.

Abstract: Formulations for enhanced mucosal absorption of heparin are disclosed. In one embodiment, a powdered heparin composition is made by dissolving an amphiphilic heparin derivative including heparin covalently bonded to a hydrophobic agent in a water phase, dispersing the water phase in an organic phase such that an emulsion is formed, and drying the emulsion. In another embodiment, an amorphiphilic heparin derivative dispersed in an oil phase is made by dissolving the amphiphilic heparin derivative in water or a water/organic co-solvent, dispersing the water or co-solvent in the oil phase, and evaporating the water or co-solvent. In another embodiment, heparin-containing nanoparticles having surfactant molecules associated with a hydrophobic agent on the outside of the nanoparticles are made by dissolving the amphiphilic heparin derivative in an aqueous solvent, mixing the surfactant with the aqueous solvent, and disrupting nanoparticles of the amphiphilic heparin derivative.

Abstract: Cerebral edema is prevented and treated by administering an effective amount of a low molecular weight heparin.

Abstract: Heparinoid derivatives comprising a chelating agent which is covalently bonded to the heparinoid, and a paramagnetic metal cation from the series of transition metals Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Mo, Ru or of the lanthanides, are suitable for producing medicaments both for therapy and for diagnostic purposes, for localizing the dose employed, and for monitoring the result of treatment of disorders such as thrombosis and osteoarthrosis.

Abstract: The invention is direct to modified heparins, especially low-molecular weight modified heparins that are adapted for used in preparing an agent for treating a skin ulcer. The low-molecular weight modified heparins have been substantially deprived of the anticoagulant activity, yet they retain the ability to bind to cell growth factors, cytokines and cell adhesion molecules.

Abstract: The present invention relates to a new hydrophobe biomolecular structure, which is compacted due to the passing of the structure over its point of collapse, a method for the preparation of the structure and use of the new structure for the manufacture of a medicament.

Abstract: Novel conjugates of glycosaminoglycans, particularly heparin and dermatan sulfate, and amine containing species and therapeutic uses thereof are described. In particular, mild methods of conjugating heparins to proteins, such as antithrombin III and heparin cofactor II, which provide covalent conjugates which retain maximal biological activity are described. Uses of these conjugates to prevent thrombogenesis, in particular in lung airways, such as found in infant and adult respiratory distress syndrome are also described.

Abstract: A biologically active conjugate is disclosed comprising a biopolymer and a therapeutic agent joined by a disulfide bond. The conjugate, when formulated in a pharmaceutical composition with a suitable carrier, has improved in vivo stability and activity, and can be targeted to a variety of cells, tissues and organs.

Abstract: The present invention relates to a composition comprising heparin to be used as a non-thrombogenic surface when in contact with arterial blood flow. It also relates to a device treated on the surface thereof with such a composition.

Abstract: This invention relates to a process for producing a desulfated polysaccharide, which comprises reacting a sulfated polysaccharide having a saccharide in which a primary hydroxyl group is sulfated, as a constituent sugar, with a silylating agent represented by the following formula (I) wherein R1s are the same or different and each represent a hydrogen atom or a halogen atom, R2 represents a lower alkyl group, and R3s are the same or different and each represent a lower alkyl group, an aryl group or a halogen atom, and a desulfated heparin obtained by this production process.

Abstract: A synthetic polysaccharide including an antithrombin III binding domain consisting of a concatenation of five monosaccharides supporting a total of two carboxylic acid functions and at least four sulpho groups, said domain being directly bound at the non-reducing end by a thrombin binding domain including a concatenation of 10-25 monosaccharide units selected from hexoses, pentoses or deoxy sugars of which all the hydroxyl groups are etherified by a C1-6 alkyl group or esterified in the form of sulpho groups, as well as salts and particularly pharmaceutically acceptable salts thereof, are disclosed.

Abstract: Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly formula (I) compounds, where the U, R and R1 groups have the meanings indicated in the description. Said glycosaminoglycan derivatives are endowed with antiangiogenic activity and are devoid of anticoagulant activity.

Abstract: Methods for detecting the presence of antibodies to PF4/heparin/TSP-1 complexes in a biological sample and for diagnosing Type 2 heparin-induced thrombocytopenia are described.

Abstract: The invention provides novel glycosaminoglycan derivatives having a repeating unit structure of two saccharides of hexosamine and hexuronic acid as a backbone structure, in which the bonds between 2- and 3-positions carbon atoms of hexuronic acid as its constituting monosaccharide are partially cleaved and a part or all of the 2-position hydroxyl groups of uncleaved hexuronic acid are not substituted with a sulfate group, which has low anticoagulation activity and excellent neurite outgrowth promotion accelerating activity and sialidase inhibition activity; a process for producing the glycosaminoglycan derivatives, comprising a cleavage treatment of the bond between the 2- and 3-position carbon atoms of hexuronic acid having no sulfate group at the 2-position of glycosaminoglycan, and a selective desulfation treatment of the 2-position sulfate group of hexuronic acid; and a pharmaceutical composition comprising the glycosaminoglycan derivative as an active ingredient.