Currently there is no effective oral prophylactic for thromboembolic disorders. As a result, afflicted individuals must receive single or multiple injections of medication each day. The effectiveness of heparin as an anticoagulant is well known. However, heparin must be administered by injection. This grant application is directed toward the development of a heparin derivative which will be an effective anticoagulant when administered orally.Phase I will demonstrate the feasibility of synthesizing heparin derivatives with hydrophobic groups, replacing a portion of the hydroxyl groups in low molecular weight heparin. It is expected that such a derivative will be orally active and have increased antithrombic activity in relation to its tendency to cause bleeding.Phase II research will entail continued synthetic work and in vitro characterization and in vivo testing of the derivative heparins in animals and in humans. Hepar Industries, with its experience in the manufacture of USP heparin, would be in a position to manufacture and market the new oral heparin developed in this project.National Heart, Lung, and Blood Institute (NHLBI)
