血液制品的现状与展望

Current status and trends in blood biologicals

摘要:

血液制品特指血浆蛋白制品和相应的重组制品。根据临床应用的效能，血液制品可以分为白蛋白类、免疫球蛋白类、凝血因子类和微量蛋白制品等不同种类。血浆白蛋白制品是最早应用于战伤救治的血液制品，高纯白蛋白、重组白蛋白以及重组白蛋白融合药物的研发和上市开创了血液制品的新局面。肌肉注射用免疫球蛋白因其制备工艺相对简单，使用方便，价格低廉且不良反应可以接受而一直在临床实践中应用；静脉注射用免疫球蛋白随着新的适应症不断发现，其应用范围越来越广；皮下注射用免疫球蛋白的出现使免疫球蛋白的使用更加方便，已经成为静脉注射用免疫球蛋白安全有效的替代品；针对特定病原体的特异性免疫球蛋白在临床上更具有不可替代的作用。凝血因子和重组凝血因子类制品主要用于相应的先天性遗传性缺陷患者，纤维蛋白原、因子Ⅶ、因子Ⅷ、von Willebrand因子复合物、因子Ⅸ和凝血酶原复合物、因子Ⅺ、因子ⅩⅢ等制品的应用取得了良好的治疗效果。因子Ⅶa和活化凝血酶原复合物对于治疗产生凝血因子抑制物的血友病病人具有十分明显的效果。纤维蛋白原类制品和凝血酶在外科止血方面发挥着重要的作用。多种微量血浆蛋白制品已经上市，如蛋白C、抗凝血酶、α1-抗胰蛋白酶和组织纤溶酶原激活剂等。部分微量血浆蛋白制品也在研发和临床试验过程中，如C1-抑制剂、补体系统Ⅰ因子、α2-巨球蛋白、血清胆碱酯酶、铜蓝蛋白以及纤维结合蛋白等。尽管多种重组血浆蛋白制品已经上市，血浆来源的制品仍将具有其不可替代的特殊地位，血浆蛋白新品种的研发仍是热点。目前，我国血液制品的研发与国外存在着较大的差距，我国血液制品企业面临着机遇与挑战。

Abstract:

Blood products are those biologicals derived from plasma or obtained by recombinant technologies. This overview covers the characteristics and classification of plasma proteins, the current status of products (albumin, immunoglobulins, coagulation factors and microcontent proteins), as well as the likely trends in the near future. Human serum albumin is one of the earliest, safest and most widely used proteins in the pharmaceutical field. The approval and development of high-purity plasma albumin, recombinant human albumin and HSA fusion proteins provide a favorable prospect for the therapeutic protein. Normal immunoglobulin contains antibodies to all the micro-organisms prevalent in the donor population. The IMIG is relatively simple to prepare and use, and the side effects are acceptable; IVIG is used mainly to treat patients with primary immunodeficiency syndromes; SCIG preparations can be used in selecting suitable patients for home therapy and have occurred fewer adverse systemic reactions; specific immunoglobulins contain concentrations of antibody to an individual organism or toxin at a higher titer than normal immunoglobulin and can not be replaced in clinical use. The plasma-derived or recombinant coagulation factors are used to treat the patients with congenital or acquired factor deficiency. The products such as Fibrinogen, FVII, FVIII, von Willebrand complex, FIX/PCC, FXI, FXIII and so on, have been widely used and proved to be effective. The development of recombinant FVIIa is now as a good bypassing product to haemophilia with inhibitors. The Fibrinogen and thrombin play a very important role in surgery hemostasis. Moreover, microcontent proteins including protein C, antithrombin, α1-AT, tPA have been licensed and used in clinical treatment; a number of other small field proteins are under produced research or pre-clinical investment. The ongoing development of new recombinant plasma proteins is providing alternatives for patients, but the distinct position and the potential impact of plasma-derived preparations are unique, furthermore the development of new plasma protein is still a hot spot in global pharmaceutics. Nowadays, a relative difference exists in the development of blood products between our nation and developed countries, so the domestic manufacturers are faced with chances and challenges.