Polysaccharides derivatives with high antithrombotic...

C - Chemistry – Metallurgy – 08 – B

Patent

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C08B 37/00 (2006.01) A61K 31/726 (2006.01)

Patent

CA 2534709

The present invention relates to a process for the preparation of sulphated glycosaminoglycans derived from N- acetylheparosan which comprises: a) N- deacetylation and N-sulphation of the N-acetylheparosan polysaccharide prepared from natural or recombinant bacterial strain, preferably K5 E. coli, b) enzymatic epimerization with the glucuronyl C5-epimerase enzyme, c) partial O-sulphation followed by a partial O-desulphation, d) partial 6-0-sulphation, e) N-sulphation and an intermediate step of controlled depolimerization characterised by the fact that both 0-sulphations (0-sulphation and 60- sulphation) are partial. Furthermore the invention relates to the products obtained according to the process which show a ratio between the anti-Xa activity and anti-Ila activity equal to or higher than 1 and to compositions comprising said products in combination with suitable and pharmaceutically acceptable excipients and/or diluent.

L'invention concerne une méthode servant à préparer des glycosaminoglycanes sulfatés dérivés de N- acétylhéparosane, ce qui consiste à effectuer: a) une N- désacétylation et N-sulfation du polysaccharide de N-acétylhéparosane préparé à partir d'une souche bactérienne naturelle ou recombinante, de préférence, K5 E. coli, b) une épimérisation enzymatique au moyen de l'enzyme glucuronyle C5-épimérase, c) une O-sulfation partielle suivie par une O-désulfation partielle, d) une 6-O-sulfation partielle, e) une N-sulfation et une étape intermédiaire de dépolimérisation contrôlée, caractérisée par le fait que les deux O-sulfations (O-sulfation et 6O-sulfation) sont partielles. Elle concerne, de plus, les produits obtenus au moyen de cette méthode et présentant un rapport entre l'activité anti-Xa et l'activité anti-IIa égal ou supérieur à 1, ainsi que des compositions contenant lesdits produits combinés à des excipients et/ou diluants adéquats et acceptables sur le plan pharmaceutique.

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