Markwardt Fritz
Pharmacology, International Institute of Thrombosis and Vascular Diseases, Frankfurt/M, Germany.
Semin Thromb Hemost. 2002 Oct;28(5):405-14. doi: 10.1055/s-2002-35292.
Advances in separation techniques and biotechnology have contributed to the development of anticoagulant agents from hematophagous animals. The most potent known natural thrombin inhibitor from blood-sucking leeches ( Hirudo medicinalis), hirudin has served as a standard for designing the natural coagulation inhibitors as an anticoagulant drug. The search for the development of hirudin from leech extract to genetically engineered products as an alternative anticoagulant has been resumed. The pharmacological profiling of the isolated thrombin inhibitor has shown that native hirudin is an antithrombotic agent of high quality. However, its clinical use has remained limited, because the substance has not been available in adequate amounts. The progress in molecular biology has stimulated the interest in the structure and function of hirudin. This development resulted in the production of recombinant hirudins (r-hirudins) through gene technology. The biological properties of hirudin combined with the ready availability of recombinant forms make the specific thrombin inhibitor well-suited for use as an antithrombotic drug. Its use should lead to a decisive progress in the management of thromboembolic diseases of both arterial and venous origin. Clinical trials, especially in diseases in which thrombin plays a crucial role, are in progress.
分离技术和生物技术的进步推动了从吸血动物中开发抗凝血剂。来自吸血水蛭（医用水蛭）的已知最有效的天然凝血酶抑制剂水蛭素，已成为设计作为抗凝血药物的天然凝血抑制剂的标准。从水蛭提取物开发水蛭素到作为替代抗凝血剂的基因工程产品的研究已重新展开。对分离出的凝血酶抑制剂的药理学分析表明，天然水蛭素是一种高质量的抗血栓形成剂。然而，其临床应用仍然有限，因为该物质的供应量不足。分子生物学的进展激发了人们对水蛭素结构和功能的兴趣。这一进展通过基因技术实现了重组水蛭素（r-水蛭素）的生产。水蛭素的生物学特性与重组形式的容易获得性相结合，使得这种特异性凝血酶抑制剂非常适合用作抗血栓药物。其应用应会在动脉和静脉源性血栓栓塞性疾病的治疗方面取得决定性进展。临床试验正在进行中，特别是在凝血酶起关键作用的疾病中。
