Abstract: Heparin-like compounds inhibit collagen-induced platelet aggregation in flowing whole blood. The compounds share properties displayed by native mast-cell derived heparin proteoglycans (HEP-PG) and/or heparin glycosaminoglycan (HEP-GAG) molecules. The compounds are useful in prevention and treatment of severe vascular disorders including arterial thrombosis.

Abstract: Preparation of synthetic monosaccharides, disaccharides, trisaccharides, tetrasaccharides and pentasaccharides for use in the preparation of synthetic heparinoids.

Abstract: A prodrug comprising a heparin and a drug is provided. The prodrug can be used to form a coating on a medical device. The prodrug can also be used with a polymeric material to form a coating on a medical device. The polymeric material can be a hydrophobic polymer, a hydrophilic polymer, a non-fouling polymer, or combinations thereof. The medical device can be implanted in a human being for the treatment of a disease such as atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, or combinations thereof.

Abstract: Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Abstract: Heparin conjugates and methods of making and use thereof are disclosed. An illustrative heparin conjugate includes a composition wherein a bile acid is bonded to heparin through the 3-carbon of the bile acid. A spacer may be interposed between the bile acid and the heparin. Another embodiment includes a targeting moiety bonded to the heparin-bile acid conjugate through a spacer. Another illustrative heparin conjugate includes heparin covalently bonded to a sulfonated moiety, such as a naphthalene trisulfonate residue. A method of treating cancer includes administering a heparin conjugate to an individual in need thereof.

Abstract: Preparation of synthetic monosaccharides, disaccharides, trisaccharides, tetrasaccharides and pentasaccharides for use in the preparation of synthetic heparinoids.

Abstract: This invention provides a method for inhibiting or preventing the abnormal growth of cells, including transformed cells, by administering an effective amount of O-acylated heparin derivative. Abnormal growth of cells refers to cell growth independent of normal regulatory mechanism (e.g. loss of contact inhibition). This includes the abnormal growth of: (1) tumor cells (tumors); (2) benign and malignant cells of other proliferative disease in which aberrant cellular proliferation occurs; (3) aberrant smooth muscle cell proliferation, such as might occur following treatment for coronary atherosclerosis such as angioplasty or the insertion of a stent into an occluded vessel.

Abstract: Described herein are crosslinked compounds useful in numerous treatments. Described herein are methods of making crosslinked compounds via (1) die oxidative coupling of two or more thiol compounds or (2) by the reaction between at least one thiol compound with at least one thiol-reactive compound.

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 relates to an anti-HIV composition and to the method for producing it. The composition of the present invention comprises a polyanion and a molecule capable of inducing the exposure of the CD4i epitope of the gp120 viral protein. The polyanion may be chosen, for example, from the group consisting of heparin, heparan sulphate, and a polyanion equivalent to heparin or to heparan sulphate. The molecule capable of inducing the exposure of the CD4i epitope of the gp120 viral protein is a CD4 peptide or a derivative thereof. The present invention also relates to the use of said composition for producing a medicinal product, in particular a medicinal product intended for the treatment of AIDS.

Abstract: Iduronic acid (IdoUA)-free heparan sulfate (HS)-like compounds are provided. Also provided are methods of synthesizing IdoUA-free HS-like compounds. The methods can include providing at least one O-sulfotransferase (OST) enzyme and a reaction mixture comprising 3?-phosphoadenosine 5?-phosphosulfate (PAPS); and incubating a polysaccharide substrate with the at least one OST and the reaction mixture, whereby the HS-like compounds are synthesized. Also disclosed are methods of synthesizing a library of HS-like compounds and methods of determining the mechanism of activity of HS-like compounds.

Abstract: The present invention provides an agent which induces acceleration of hard tissue formation, acceleration of cell differentiation and increase in cellular alkaline phosphatase activity, by directly acting on the cell. Specifically, it provides a hard tissue formation promoter, a cell differentiation inducer and a cellular alkaline phosphatase activity reinforcing agent comprising, as an active ingredient, a glycosaminoglycan or a salt thereof that keeps sulfate group and has the characteristics of the following (1) and (2): (1) a basic structure is a disaccharide repeating structure consisting of a hexuronic acid residue and a glucosamine residue, (2) one or less of the position among a 2-position hydroxyl group of a hexuronic acid residue, a 6-position hydroxyl group of a glucosamine residue and a 2-position amino group of the glucosamine residue in the basic structure of the aforementioned (1) does not have the sulfate group.

Abstract: Disclosed herein are conjugates comprising a nanocarrier, a therapeutic agent or imaging agent and a targeting agent. Also disclosed herein are compositions comprising such conjugates and methods for using the conjugates to deliver therapeutic and/or imaging agents to cells. Also disclosed are methods for using the conjugates to treat particular disorders, such as proliferative disorders.

Abstract: The invention provides a process for preparing heparin products with a reduced content of glycoserine. A method for detecting glycoserine in preparations of heparin is also provided.

Abstract: A thromboresistant coating for a medical device, method of coating and coated medical device, the coating including an in situ cross-linked co-polymer of a cross-linkable biomolecule, preferably an adsorbable biomolecule such as a heparin activity biomolecule with at least one prosthetic hydrophobic unit, and a multifunctional crosslinking agent, such as a bis-variant of polyethylene glycol, polyethylene oxide, or polyethylene glycol, wherein the crosslinking is by means of covalent complexation through at least two functional groups of the multifunctional crosslinking agent.

Abstract: A method and medicament for treating and preventing platelet activation or thrombosis in the presence of heparin-and platelet factor 4-complex reactive antibodies using a 2-O desulfated heparin with an average degree of sulfation of 0.6 sulfate groups per monosaccharide or greater and an average molecular weight or 2.4 kD or greater. The medicament preferably is administered intravenously, by aerosolization or orally. Preferably, the 2-O desulfated heparin medicament includes a physiologically acceptable carrier which may be selected from the group consisting of physiologically buffered saline, normal saline, and distilled water. Additionally provided is a method of synthesizing 2-O desulfated heparin.

Abstract: The invention relates to compounds capable of releasing nitric oxide wherein the compounds comprise a saccharide and at least one nitric oxide-releasing diazeniumdiolate [N2O2] functional group, which is bonded directly to a carbon atom of the saccharide, and methods for preparing the same. The invention further comprises the treatment of biological disorders treatable by the administration of nitric oxide.

Abstract: The present invention relates to a method for preparation of heparin silver, to use of heparin silver in manufacture of medicine for treating burns and/or scalds, to a method of using heparin silver to treat burns and/or scalds, and to a topic topical preparation containing heparin silver for treating burns and/or scalds. The heparin silver product prepared according to the method of the present invention has a high purity and less impurity. The animal test proved that the medicine made by using heparin silver exhibited effects of accelerating wound healing and reducing scar formation.

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 composition and methods for the synthesis of low molecular weight heparins and heparinoids. The present invention also provides compositions having substantially homogenous populations of desired heparin molecules, or molecules useful in the synthesis of heparin oligosaccharides.

Abstract: This invention provides compounds represented by the structure of the general formula (A): wherein L is a lipid or a phospholipid, Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol, Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, X is a physiologically acceptable monomer, dimer, oligomer, or polymer, wherein X is a glycosaminoglycan; and n is a number from 1 to 1000, wherein any bond between L, Z, Y and X is either an amide or an esteric bond.

Abstract: The present invention relates generally to chemical agents useful in the prophylaxis and/or treatment of disease conditions and in particular chronic disease conditions such as inflammatory including allergic diseases, metastatic cancers and infection by pathogenic agents including bacteria, viruses or parasites. More particularly, the chemical agents contemplated by the present invention are selected from glycosaminoglycan (GAG) molecules derived from a larger GAG, GAG-like molecules which resemble GAGs in some of their characteristics but may be derived from a larger non-GAG polysaccharide and molecules having a GAG-like composite structure as well as agents which bind to the same sites as GAGs, GAG-like molecules or GAG-like composite molecules. The present invention also provides assays to identify GAG and GAG-like therapeutic agents including GAG-like composite structures as well as analogs, homologs and orthologs thereof.

Abstract: Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly a compound of formula (I) where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives have antiangiogenic and heparanase-inhibiting activity and are devoid of anticoagulant activity.

Abstract: Substances comprising carboxylated and/or sulfated oligosaccharides in substantially purified form, including compositions containing same and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of Tumor Necrosis Factor Alpha (TNF-?) can be either inhibited or augmented selectively by administration to the host of effective amounts of substances or their compositions comprising specific oligosaccharides in substantially purified form. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and/or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF-?. The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be daily, at very low effective doses, typically below 0.

Abstract: Described herein are compounds such as macromolecules that have been modified in order to facilitate crosslinking by introduction of at least one hydrazide-reactive group and/or aminooxy-reactive group, and methods of making and using thereof for scar-free wound healing, for delivering bioactive agents or living cells, for preventing adhesion after a surgical procedure or for bone and cartilage repair. The macromolecule can be an oligonucleotide, a necleic acid, a polypeptide, a lipid, a glycoprotein, a glycolipid, a polysaccharide, a protein or a synthetic polymer, preferably a glycosaminoglycan like hyaluronan.

Abstract: The present invention provides charged separation media, kits comprising the separation media, and methods of using the same to bind and optionally isolate biological molecules. The charged separation media and methods utilize a polyion non-covalently bound to the separation media to bind the desired biological molecule to the separation media.

Abstract: The invention relates to a process for the depolymerization of glycosaminoglycanes characterized by the use of electron beam radiation, optionally 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 the intermediate depolymerized heparin obtained by the process. 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 oral formulations of Sulodexide for the treatment of diabetic nephropathy in patients with both insulin dependent and non-insulin dependent diabetes mellitus. Oral formulations containing doses adapted for administration to obtain a reduction in albumin excretion in patients with both micro and macro albuminuria and to produce lasting improvement in albumin excretion rate are provided. Methods of treating diabetic nephropathy using these formulations are also provided.

Abstract: The object of the present invention is to provide a composition which exerts a higher effect on recovering health from articular disorders than that attained by amino sugars and glycosaminoglycans. The present invention solves the object by providing an agent for treating articular disorders, comprising an amino sugar and trehalose as effective ingredients.

Abstract: The present invention describes the use of polysaccharide derivatives for the preparation of biocompatible and biodegradable biomaterials with absorbent properties for body fluids and physical hemostatic activity, to be used in both venous and arterial vascular anastomoses to create a physical hemostatic barrier and to prevent scar tissue formation and formation of post-surgical adherence of the vessels to the surrounding tissues.

Abstract: The present invention provides hydrophobic heparin conjugates that are soluble in organic solvents but not in water, a method of preparing them, and a method of using them. Particularly, the present invention provides hydrophobic heparin conjugates that are prepared by covalently binding a polymer to heparin and a hydrophobic agent to the polymer. The hydrophobic heparin conjugates of the present invention maintain a good antithrombogenic effect and are insoluble in water due to their hydrophobicity, so they can be effectively used as coating agents for modifying the surfaces of medical devices.

Abstract: The invention provides novel methods for treating disease based upon the medicinal use of lipids and phospholipids covalently bound to physiologically acceptable monomers or polymers. Phosphatidylethanolamine moieties conjugated to physiologically acceptable monomers and polymers (PE conjugates) manifest an unexpectedly wide range of pharmacological effects, including stabilizing cell membranes; limiting oxidative damage to cell and blood components; limiting cell proliferation, cell extravasation and (tumor) cell migratory behavior; suppressing immune responses; and attenuating physiological reactions to stress, as expressed in elevated chemokine levels.

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 a molecular weight of between 1,000 and 5,500, absorbance at 400 nm below 0.300 and ratio SO3?/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: 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: The invention provides novel methods for treating disease based upon the medicinal use of lipids and phospholipids covalently bound to physiologically acceptable monomers or polymers. Phosphatidylethanolamine moieties conjugated to physiologically acceptable monomers and polymers (PE conjugates) manifest an unexpectedly wide range of pharmacological effects, including stabilizing cell membranes; limiting oxidative damage to cell and blood components; limiting cell proliferation, cell extravasation and (tumor) cell migratory behavior; suppressing immune responses; and attenuating physiological reactions to stress, as expressed in elevated chemokine levels.

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: A process for prophylaxis and therapy of thrombotic processes includes preparing heparin having an average molecular weight ranging from 10 to 11.5 kd; formulating a pharmaceutical preparation which includes the heparin; and employing the pharmaceutical preparation for prophylaxis and therapy of thrombotic processes. Preferably the heparin has an average molecular weight of 10.5 kd.

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 polysaccharides essentially formed of units of uronic acid and/or hexosamine, with subsituents containing a ONO2 ? group.

Abstract: The present invention relates to folic acid-polysaccharide complexs and method of preparation thereof, more particularly relates to folic acid-Dextran complexs, method of preparation thereof, pharmaceutical compositions having said complex as active component and uses of said composition in therapy of tumors. The folic acid-polysaccharide complexs of the present invention have general formula of: (X)n—Y, wherein X is identical or different, and is selected from folic acid, derivatives of folic acid and other substances that can enter into cell via the pathway of folic acid receptor; Y is polysaccharide; n?1.

Abstract: Alkali and alkali-earth metal salts of polysaccharides derived from heparin, their method of preparation and the pharmaceutical compositions containing them.

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: A water insoluble, biocompatible composition that is formed by a method which combines, in an aqueous mixture, a polyanionic polysaccharide, a nucleophile, and an activating agent, under conditions sufficient to form the composition. Also, a water insoluble, biocompatible composition that is formed by a method which combines, in an aqueous mixture, a polyanionic polysaccharide, a modifying compound, a nucleophile and an activating agent under conditions sufficient to form the composition.

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 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: The instant invention provides a method of treating or preventing osteoarthritis, joint effusion, joint inflammation and pain, synovitis, lameness, post operative arthroscopic surgery, deterioration of proper joint function including joint mobility, the reduction or inhibition of metabolic activity of chondrocytes, the activity of enzymes that degrade cartilage, the reduction or inhibition of the production of Hyaluronic acid, said method comprising orally administering to a mammalian species a therapeutically effective amount of Hyaluronic Acid or pharmaceutically acceptable salts thereof. Additionally, compositions containing hyaluronic acid; chondroitin sulfate, and glucosamine sulfate in a paste formulation are also disclosed which can be administered on their own or can be used as a feed additive.

Abstract: The present invention provides a bioactive coating composition, method and devices for bodily fluid-contacting surfaces. The coating comprises a complex of Formula II: wherein R1 is an C1-18alkyl or C6-32aryl group, each R2 is independently selected from the group consisting of C1-18alkyl and C6-32aryl, R3 is N or O, n is a number from 1 to 10, and x in a number from 1 to about 30, directly bound to a heparin-activity molecule via covalent bonding, with one or more bioactive molecules bound to the heparin-activity molecule.

Abstract: The present invention refers to the preparation of O-sulphated, N-sulphatated or N-acetylated derivatives, both epimerised or non epimerised, of K5, K4, and optionally defructosilated K4 and K40 polysaccharides and to their use as antiinflammatory agents in chronic and acute inflammations.

Abstract: Process for bulk autoclaving of polysaccharides, wherein the process includes: a) dissolving the polysaccharides in an aqueous solution and mixing until a homogeneous solution is obtained; b) filling the resulting solution in at least one container; c) placing the filled container(s) including the solution in an autoclave; d) placing a sensor in at least one of the containers; and e) autoclaving the filled containers.

Abstract: The present invention relates to novel synthetic polysaccharides with antithrombotic activity exhibiting at least one covalent bond with biotin or a biotin derivative and to a process employing avidin or streptavidin which makes it possible to neutralize these polysaccharides.

Abstract: Heterogeneous intimate admixtures of sulfated heparinic polysaccharides, well suited for the prophylaxis/treatment of acute thrombotic episodes in a human patient, comprise immixture of sulfated polysaccharides having a weight average molecular weight less than that of heparin and which include from 9% to 20% of polysaccharide chains having a molecular weight less than 2,000 daltons and from 5% to 20% of polysaccharide chains having a molecular weight greater than 8,000 daltons, the ratio between the weight average molecular weight and the number average molecular weight thereof ranging from 1.3 to 1.6.