Synthesis and bioactivity of copolymers with fragments of heparin

Abstract

A new type of biocompatible copolymer comprising small fragments of heparin, (octa- to dodecasaccharides) copolymerized with a synthetic monomeric component, viz. acrylamide, has been prepared. The heparin fragments are produced by enzymatic or chemical means and are copolymerized, directly or after suitable derivatization, with acrylamide as the major polymerizable component. The polymeric material incorporates the heparin segments as pendant moieties such that their essential functional groups and structural features for specific binding with the selective serine protease coagulation factor inhibitor antithrombin III are preserved. An important feature of this copolymer is its biocompatibility which relates specifically to its antithrombotic and antithrombogenic activity derived from those of heparin fragments. The biological activity of heparin fragments and copolymers thereof are determined in terms of APTT and anti-Xa activity, their antithrombotic potential being expressed as a ratio of anti-Xa activity to APTT. The copolymers reported have biological activities similar to equivalent amounts of respective heparin fragments, and show higher antithrombotic activity compared to intact heparin or commercially available low-molecular-weight heparin (4,000-6,000 Da).