Liu Zhang, Ji Shengli, Sheng Juzheng, Wang Fengshan
Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Shandong University.
Drug Discov Ther. 2014 Feb;8(1):1-10. doi: 10.5582/ddt.8.1.
Heparin, one of the common anticoagulants, is clinically used to prevent and treat venous thromboembolism (VTE). Though it has been the drug of choice for many advanced medical and surgical procedures with a long history, the adverse events, such as bleeding, heparin-induced thrombocytopenia (HIT), allergic reactions, follow. Therefore, low molecular weight heparins (LMWHs) and ultra low molecular weight heparins (ULMWHs), with lower molecular weights, higher anti-FXa activity, longer half-life times and lower incidence of adverse events than unfractionated heparin (UFH), were researched and developed. Fondaparinux, a chemically synthesized ULMWH of pentasaccharide, has the same antithrombin III (AT-III)-binding sequence as found in UFH and LMWH. In addition, AVE5026 and RO-14, another two ULMWHs, are obtained by selective chemical depolymerization. In this paper, we review the preparation process, pharmacological effects and clinical applications of fondaparinux, AVE5026 and RO-14.
肝素是常用的抗凝剂之一，临床上用于预防和治疗静脉血栓栓塞症（VTE）。尽管它长期以来一直是许多先进医疗和外科手术的首选药物，但仍会出现出血、肝素诱导的血小板减少症（HIT）、过敏反应等不良事件。因此，人们研发了低分子量肝素（LMWHs）和超低分子量肝素（ULMWHs），它们的分子量更低、抗FXa活性更高、半衰期更长，且不良事件的发生率低于普通肝素（UFH）。磺达肝癸钠是一种化学合成的五糖超低分子量肝素，具有与普通肝素和低分子量肝素相同的抗凝血酶III（AT-III）结合序列。此外，另外两种超低分子量肝素AVE5026和RO-14是通过选择性化学解聚获得的。在本文中，我们综述了磺达肝癸钠、AVE5026和RO-14的制备工艺、药理作用及临床应用。
