《胰岛素的类别》ppt课件.ppt

* 门冬胰岛素能真正模拟胰岛素的餐时分泌。 而在夜间模拟基础胰岛素水平的NPH却不是令人满意。 理想的基础胰岛素应该提供连续的释放，即所谓方波。 这就是可溶性，长效胰岛素类似物的作用。 This old modeling by Polonsky show that with insulin aspart it is indeed possible to mimick the insulin response to a meal in non-diabetics using a rapid-acting insulin such as insulin aspart. The mimicking of basal insulin during the night using NPH is less satisfactory. The ideal basal insulin should provide constant release – so-called square wave – during the night. This is where the soluble, protracted insulin analogues will find use. * 来得时? （甘精胰岛素）是通过重组DNA技术生产获得的长效人胰岛素类似物1 B链增加了2个精氨酸使等电点从 pH 5.4 增至 pH 6.72 甘氨酸在A21位取代天冬氨酸形成更稳定的六聚体2 来得时?可溶解于弱酸性环境 （pH 4）， 但在皮下组织的中性pH条件下沉淀1 PH的改变使来得时在皮下组织形成细微沉淀，从而延缓吸收，延长作用时间1 来得时? ，每天注射一次，在首次给药后2到4天达到稳态水平， 在注射12天后没有证据表明存在药物蓄积1 延长甘精胰岛素作用时间的因素 ?精氨酸替代 （B31） （使作用时间延长2个小时） ?第二个精氨酸替代 （B32）（ 降低Di-Arg-晶体的溶解度。与天冬氨酸结合 （A30）） ?天冬氨酸被甘氨酸（A21）所取代（分子间相互作用力减少） ?pH 4时溶解 （皮下注射后沉淀的条件） 1. Lantus? (insulin glargine) EMEA Summary of Product Characteristics. Bridgewater, NJ: Aventis Pharmaceuticals; 2002. 2. McKeage K, Goa KL. Insulin glargine: a review of its therapeutic use as a long-acting agent for the management of type 1 and type 2 diabetes mellitus. Drugs. 2001;61:1599-1624. * 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 extends the activity by reducing the absorption rate from the injection site3 1. Kramer W. New approaches to the treatment of diabetes. Exp Clin Endocrinol Diabetes. 1999;107(suppl 2):S52-S61. 2. Lantus? (insulin glargine) EMEA Summary of Product Characteristics. Bridgewater, NJ: Aventis Pharmaceuticals; 2002. 3. McKeage K, Goa KL. Insulin glargine: a review