DM的药物治疗同学-培训课件.ppt

胰岛素不断研发进步的趋势是动物胰岛素逐渐被人胰岛素所替代, 人胰岛素将会在未来的几年中被胰岛素类似物逐步替代. 目前全球胰岛素类似物量的使用率已经占到胰岛素市场的?%, 对于使用人胰岛素的患者,胰岛素类似物能够更好地模拟生理性胰岛素分泌模式,能够更好的控制餐后血糖及减低夜间及严重低血糖的发生率,这也正是胰岛素类似物在市场中使用迅速增长, 而人胰岛素将逐步被升级为胰岛素类似物的原因所在. 纯度——由于存在提纯不好，注射部位可以出现脓肿等不良反应，解决方法：采用重结晶法生产单峰胰岛素。 抗体——由于与人胰岛素有结构的差异，可以产生胰岛素抗体，产生胰岛素抗药性、循环中的结合抗体的胰岛素与抗体分离可以发生不可预知的低血糖；解决办法：人胰岛素 酸性溶液——引起注射疼痛，解决办法：加入磷酸缓冲液，变为中性 来看看目前常用的人胰岛素制剂：按剂型分 正是由于目前胰岛素制剂存在不足，才引发了我们对新的能同时满足医生和患者的需求的胰岛素的研究。 Dissociation and Absorption of NovoLog? Hexamers are the principal association state found in pharmaceutical formulations of neutral soluble (regular) human insulin. 六聚体是中性可溶性人胰岛素的主要存在形式。当人胰岛素注射到皮下稀释后，六聚体释放结合的锌离子，缓慢解离为双体和单体，由于六聚体的吸收较单体和双体慢的多，解聚的速度限制了吸收的速度。鉴于可溶性人胰岛素的吸收慢，餐前大剂量需要在餐前30分钟给予以使血浆胰岛素跟血糖同步达峰。由于给药时间的不方便，所以很多患者在餐前即刻给药。 After human insulin is injected and becomes diluted, hexamers release bound zinc ions and slowly dissociate into dimers and monomers. Since hexamers are absorbed at a much slower rate than dimers and monomers, the dissociation process imposes limitations on the rate of insulin absorption. Due to the slow rate of absorption of regular human insulin, bolus doses should be injected approximately 30 min before a meal in order to allow monomeric insulin to reach the circulation before glucose levels rise. Many people administer their insulin immediately before a meal because of the inconvenient dosing restrictions. Brange J, Owens DR, Kang S, Volund A. Monomeric insulins and their experimental and clinical implications. Diabetes Care. 1990;13:923-954. 来得时?是B31-B32-精氨酸人胰岛素，在A21位置门冬酰胺为甘氨酸替代。这使等电点由天然胰岛素的5.4变为7.0。 The prolonged action of Lantus? (insulin glargine) is based on a slow dissolution of a microprecipitate1,2 After injection into subcutaneous tissue, the acidic Lantus solution is neutralised, leading to formation of microprecipitates from which small amounts of Lantus are slowly released1,2 The presence of zinc in the Lantus preparation is required for formation of microprecipitates in the subcutaneous tissue and exte