Conjugates of biologically active substances

US6011008A · kind A · utility

Assignee

• YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD. · IL

Inventors

• Abraham J. Domb · Beer Sheva, IL
• Shimon Benita · Mevaseret Tsiyon, IL
• Itzhack Polacheck · Jerusalem, IL
• Galina Linden · Rishon LeZion, IL

Key dates

• Filing date: Jun 4, 1998
• Grant date: Jan 4, 2000
• Expiry date: Jun 4, 2018

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K47/61
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A method for producing a water-soluble polysaccharide conjugate of an oxidation-sensitive substance is described. The method comprises the following steps: (a) activating the polysaccharide to a dialdehyde by periodate oxidation; (b) purifying the dialdehyde from interfering anions and by-products; and (c) coupling the substance to the purified dialdehyde by Schiff base formation to form the conjugate. Optionally, the conjugate of step (c) is reduced to an amine conjugate by a reducing substance. The product conjugate may then be further purified from various reaction byproducts. The disclosed method results in the substance substantially retaining its biological activity. Also described are imine and amine polysaccaride conjugates of various drugs and polypeptides.