New biocompatible polyurethane-type copolymer with low molecular weight heparin

Abstract

A new polyurethane-type block copolymer comprised of a small fragment of heparin, viz. low molecular weight heparin (LMWH), and a diisocyanate together with an additional polyhydroxy component was prepared. The heparin fragment was obtained by chemical depolymerization with nitrous acid (deaminative cleavage), and this was copolymerized, after suitable modification or derivatization, by addition reaction of the isocyanate and the polyol components. Alternatively, the copolymerization was carried out prior to a simple derivatization step with the heparin fragment. The copolymer incorporates in its backbone the heparin fragment as a pendant moiety so that its essential functional groups and structures required 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 specifically relates to the antithrombotic as well as antithrombogenic (non-thrombogenic or thromboresistant) properties derived essentially from those of the heparin fragment. The biological activity of copolymers containing the heparin fragment is determined in terms of activated partial thromboplastin time (APTT) and anti-Xa activity, the antithrombotic potential being defined as the ratio of anti-Xa activity to APTT.