肝素生物测定法的研究进展

Progress in Study of Biological Assay of Heparin

肝素是临床上广泛使用的天然抗凝血和抗血栓药物,按照分子质量分级可以分为:普通未分级肝素、低分子量肝素和超低分子量肝素,不同分子质量肝素所具有的生物学特性各不相同。对肝素效价的把控是肝素产品质量控制的重要一环,生物测定法可以综合反映所有的可变效应,能够监测药品在生产过程中难以料想、不易发现的构象变化,是含量测定所不能实现的。目前,从各国药典中收载的肝素效价测定方法来看主要有以下5种:1.全血法(兔、猪或羊);2.血浆均值法;3.血浆复钙法;4.活化凝血酶时间法(APTT);5.生色底物法;应用这些方法在肝素的生物效价检测方面已经具有比较成熟的发展。文章对肝素效价生物测定法研究进展进行梳理和总结,并探讨这些方法各自的优势和不足。

Heparin is a natural anticoagulant and antithrombotic glycosaminoglycan drug,which has been widely used in clinical practice as an anticoagulant to prevent and treat arterial and venous thrombosis due to its relative ease of use,safety,and low cost.The anticoagulant properties result from the ability of the polysaccharide to enhance the rate of inactivation of blood coagulation pro-teinases by their natural protein inhibitors,the most important of which is antithrombin.It is a heterogeneous,linear,highly sulfated,anionic glycosaminoglycan with a broad distribution in relative molecular weight and charge density.Heparin can be divided into unfractionated heparin(UFH),low-molecular-weight heparin(LMWH),and ultralow-molecular-weight heparin(ULMWH)by molecular weight,which is administered systematically,and all of them have been developed by several manufacturers and have advantages in terms of pharmacokinetics and convenience of administration.The biological characteristics and biological activities of heparin with different molecular weights vary.The control of heparin potency is an important part of quality control.Biological assay is capable of comprehensively reflecting all variable effects and monitor conformational changes that are difficult to anticipate and detect during production,which cannot be achieved by chemical assay.At present,there are five main methods for estimating the potency of heparin in pharmacopoeias of various countries:1.the blood method(rabbit,pig,or sheep);2.the moving average method;3.the plasma recalcification method;4.the activated partial thromboplastin time(APTT)method;5.the chromogenic substrate method.The application of these methods in the biological potency estimation of heparin has developed well and widely used.This article reviewed and summarized the study and research progress of biological assay of heparin,discussed the advantages and disadvantages of these methods,and proposed prospects for the future development of heparin biological assay.