Orally Active Heparin Derivatives for the Prevention of Deep Vein Thrombosis and Pulmonary Embolism

摘要

@@1 Background Heparin is one of the most potent anticoagulants and is widely used for the treatment and the prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE). However, the main disadvantage of heparin treatment is that it is available to patients only by parenteral administration. Upon discharge from the hospital, patients are usually switched from heparin to warfarin because warfarin can be administered orally. Warfarin, however, has a slow onset and is subjected to a high possibility of drug-to-drug interactions, which is why oral heparin is in great need. The need for an efficacious and safe oral anticoagulant that does not require monitoring has been largely unmet. Many efforts have centered on preparing orally available heparin to improve patient compliance. In this study, novel orally active heparin derivatives (LHD), i.e. low molecular weight heparin (LMWH) conjugated with deoxycholic acid (DOCA), were evaluated in vitro and in vivo to enhance its oral absorption.