生物制药 基因工程药物课件.pptVIP

Chemical mediators Released by platelets Platelets cover and adhere to exposed subendothelial surface + Activation of coagulation factors in plasma Prothrombin (II) Thrombin (IIa) Fibrinogen(I) Fibrin 1 2 3 4 Formation of a hemostatic plug Damage to vessel expose collagen to subendothelium Platelet adhesion and release of granules Platelet aggregation and formation of fibrin plug 1 3 2 TXA2 TXA2 Aspirin AA PGG2, PGH2 Platelet TXA2 binds to receptors on other platelets thereby initiating release of additional aggregating agents. DAG IP3 ATP cAMP 5`-AMP Dipyridamole PGI2 5-HT ADP Balance between levels of PGI2 and TXA2 influences whether platelet aggregates or circulates freely Healthy, intact endothelium releases PGI2 into plasma. PGI2 binds to platelet membrane receptors causing synthesis of cAMP. cAMP inhibits release of granules containing aggregating agents. Thrombin, TXA2 and exposed collagen cause release of AA from platelet membrane. TXA2 is synthesized from AA and released from the platelet. This pathway is inhibited by aspirin. Endothelial cells Collagen fibers Granules 中性鱼精蛋白胰岛素Neutral Protamine insulin Hagedorn (NPH) 属中效制剂 鱼精蛋白与胰岛素二者的量相匹配，0.4 mg/100 iu，鱼精蛋白无多余 二者呈相当的比份(Isophane proportion) 只需加微量的锌使制剂稳定：锌0.016 ~ 0.04 mg/100 iu NPH与RI混合应用时，由于无多余的鱼精蛋白，故RI不被吸附，以速效形式存在 目前有各种比例的预混胰岛素(Premixed insulin)NPH/RI:70/30,80/20,60/40 长效胰岛素的发展鱼精蛋白与胰岛素结合型缓效胰岛素研制成功 Hagcdorn 1936 鱼精蛋白(Protamine)为雄鱼生殖腺所含的一组碱性蛋白质 pH中性的胰岛素加入鱼精蛋白后，其溶解度降低，形成胰岛素－鱼精蛋白复合沉淀物 注射至皮下组织后，蛋白酶将鱼精蛋白分解下来，胰岛素逐渐释出 有两种主要的制剂 国内常用胰岛素一览表 产品名包装(U/瓶) 生产厂家 种属来源 短效胰岛素 中性胰岛素(RI) 400 U/瓶 上海生物制药厂 猪 常规优泌林 400 U/瓶 礼来 人 (Humulin-R) (人工合成) 诺和灵-R 400 U/瓶 诺和诺德 人 (Actrapid-P) (人工合成) 诺和灵-R 150 U/瓶 诺和诺德 人 (笔专用) (人工合成) Lispro 400 U/瓶 礼来 人 中效胰岛素 中效优泌林400 U/瓶