Patent classifications
C08B37/0078
DERIVATIVES OF N-DESULFATED GLYCOSAMINOGLYCANS AND USE AS DRUGS
A glycosaminoglycan derivative which is obtainable by a process that includes the steps of N-desulfation of from 25% to 100% of the N-sulfated residues of a glycosaminoglycan, and oxidation, by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N-, 3-O-non-sulfated glucosamine residues, and of the 2-O-non-sulfated uronic acid residues of said glycosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NH.sub.2 to aldehydes. The process further includes reduction, by sodium borohydride, of said oxidized glycosaminoglycan, under conditions effective to convert said aldehydes to alcohols, where the glycosaminoglycan is heparin, low molecular weight heparin, heparan sulfate or fractions thereof.
EXPEDIENT SYNTHESIS OF CORE DISACCHARIDE BUILDING BLOCKS FROM NATURAL POLYSACCHARIDES FOR HEPARAN SULFATE OLIGOSACCHARIDE ASSEMBLY
Methods for the preparation of oligosaccharide products from polysaccharide starting materials are disclosed. The methods include: hydrolyzing a glucosamine-containing polysaccharide starting material, such as heparin or heparosan, under conditions sufficient to form an oligosaccharide intermediate (e.g., a GlcN-IdoA disaccharide intermediate or a GlcA-GlcN disaccharide intermediate), and converting the oligosaccharide intermediate to the oligosaccharide product. Conversion of the oligosaccharide intermediates to the oligosaccharide products may include one or more esterification, acylation, epimerization, protection, and deprotection steps. Preparation of higher-order oligomers is described, as well as methods for selective oligosaccharide sulfation.
CARBOXYLATED DERIVATIVES OF GLYCOSAMINOGLYCANS AND USE AS DRUGS
A glycosaminoglycan derivative endowed with heparanase inhibitory activity and antitumor activity, bearing carboxylate groups in positions 2 and 3 of at least part of the glycosaminoglycan residues, and to the process for preparing the same. The glycosaminoglycan derivatives of the present invention are generated starting from natural or synthetic glycosaminoglycans, preferably heparin or low molecular weight heparin, optionally 2-O- and 2-N-desulfated by two steps of oxidation. By the first oxidation, adjacent dials and optionally adjacent OH/NH.sub.2 of the glycosaminoglycan residues are converted to aldehydes and by the second oxidation said dialdehydes are converted to carboxylate groups. The first oxidation preferably leads to the cleavage of C2-C3 linkage of the ring of oxidable residues. The invention relates to a process for the preparation of said glycosaminoglycan derivatives and to their use as active ingredients of medicaments.
CARBOXYLATED DERIVATIVES OF GLYCOSAMINOGLYCANS AND USE AS DRUGS
A glycosaminoglycan derivative endowed with heparanase inhibitory activity and antitumor activity, bearing carboxylate groups in positions 2 and 3 of at least part of the glycosaminoglycan residues, and to the process for preparing the same. The glycosaminoglycan derivatives of the present invention are generated starting from natural or synthetic glycosaminoglycans, preferably heparin or low molecular weight heparin, optionally 2-O- and 2-N-desulfated by two steps of oxidation. By the first oxidation, adjacent dials and optionally adjacent OH/NH.sub.2 of the glycosaminoglycan residues are converted to aldehydes and by the second oxidation said dialdehydes are converted to carboxylate groups. The first oxidation preferably leads to the cleavage of C2-C3 linkage of the ring of oxidable residues. The invention relates to a process for the preparation of said glycosaminoglycan derivatives and to their use as active ingredients of medicaments.
METHOD OF DEGRADING POLYSACCHARIDE USING OZONE
The present invention relates to a method for degrading a polysaccharide in the field of food, medicine or chemical industry. In particular, a molecular chain of the polysaccharide is broken by ozone into polysaccharides with smaller molecular weights, oligoses and/or oligosaccharides. The polysaccharides include linear or branched glycans extracted from plants, traditional Chinese medicinal materials, animals, fungi, or microorganisms and sulfated polysaccharides or esterified polysaccharides formed by sulfation or esterification thereof. As an oxidizing agent in the reaction, the ozone can be used alone or can be used under the catalysis of a base, a metal ion, hydrogen peroxide, UV light, or activated carbon to accelerate the reaction. The method for degrading the polysaccharide in the present invention uses milder reaction conditions compared to a conventional acid-catalytic degradation method, has higher reaction efficiency and a controllable reaction process, does not need to use an acid, and reduces environmental pollution.
Heparan sulphates
A novel class of structurally and functionally related isolated Heparan sulphate is disclosed. The novel class of Heparan sulphates has been found to bind FGF2 and enhance the proliferation of stem cells while maintaining their pluripotency/multipotency.
Glycosaminoglycans
Heparan sulphate HS7 is disclosed, together with the use of HS7 in the growth and/or development and/or regeneration of tissue.
SULFATED HEPARIN OLIGOSACCHARIDE AND PREPARATION METHOD AND APPLICATION THEREOF
Provided are a sulfated heparin oligosaccharide as well as a preparation method and an application thereof. The sulfated heparin oligosaccharide molecule contains an unsaturated double bond resulting from enzymolysis by heparinase at the non-reducing end thereof, an uronic acid derivative and a glycosylamine derivative; and has a structure represented by formula I, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.a, R.sub.b, R.sub.c, R.sub.d; R.sub.x, R.sub.y, R.sub.z, and n are as defined herein. The preparation method obtains a sulfated oligosaccharide with a controllable degree of sulfation. The sulfated heparin oligosaccharide has a high activity for inhibiting heparanase in vitro, with an activity 4-5 times higher than that of heparin for inhibiting cell adhesion and migration, and an activity 2-3 times higher than that of heparin for resisting tumor metastasis in mice, thus having a relatively good effect in resisting tumor metastasis and a relatively high specificity.
Modulation of the physical interaction between platelets and the cell surface effecting cell proliferation
The growth and/or proliferation of mammalian cells are modulated by modulating the physical interaction between platelets (thrombocytes) and the surface of the cells. Sulfated polysaccharides, preferably glycosaminoglycans, can be used as a medicament for the inhibition of the physical interaction between the cell surface and platelets in the treatment of a medical disorder associated with unwanted cell growth and/or proliferation. The physical interaction between platelets (thrombocytes) and the surface of the cells can be modulated in vitro in order to modulate cell proliferation. Inhibition of the interaction between the cell surface and platelets can inhibit cell growth, and enhancement of the interaction between platelets and the surface of the cell can enhance cell growth.
PDGF-B /PDGF-BB BINDING VARIANTS OF HEPARAN SULFATES
Affinity purification of platelet-derived growth factor-binding heparan sulphate from porcine mucosa (HS6) is disclosed. Also disclosed is the use of HS6 in repair and regeneration of the skin for treating wounds, burns, ulcers and other skin injuries.