第六治疗用激素.pptVIP

Charpter 6 Incretion applied to treatment What We Will Cover Diabetes and insulin Before Insulin Before insulin was discovered in 1921, everyone with type 1 diabetes died within weeks to years of its onset 1922 Leonard Thompson In Jan, 1922, Banting and Best injected a 14-year-old charity” patient who weighed 64 lb with 7.5 ml of a thick brown muck in each buttock Abscesses developed and he became more acutely ill However, his blood glucose had dropped enough to continue refining what was called iletin” insulin 6 weeks later, a refined extract caused his blood glucose to fall from 520 to 120 mg/dL in 24 hours Leonard lived a relatively healthy life for 13 years before dying of pneumonia (no Rx then) at 27 Insulin Production Begins First produced as “Connaught” by the Univ of Toronto On May 30, 1922, Eli Lilly signed an agreement to pay royalties to the University to increase production First bottles contained U-10 insulin 3 to 5 cc were injected at a time Pain and abscesses were common until purer U-40 insulin became available Impact Of Insulin OnLife Expectancy By The 1940’s 胰岛素的化学性质 本品为白色或类白色结晶粉末，是从猪或牛胰中提取制得的。据精制方法不同，有两种形态：不规则细粉颗粒(无定形)和扁斜形六面体。 可溶于稀醇、稀丙酮、酸、碱中，不溶于90%以上乙醇及其他有机溶剂，在pH 2-4时更稳定，在碱性介质中易破坏，加热易变性。遇蛋白酶、强酸、强碱均能破坏。等电点pH 5.3-5.4，易与锌、镉、钴等2价金属结合。药用常制成锌胰岛素，与鱼精蛋白能形成复合体，且作用时间较长。 传统生产工艺：常规胰岛素① 常规胰岛素制剂： 保存在较低的pH 2.5-3.5 现代动物来源的胰岛素制剂 ②单峰胰岛素：并非均一的制剂 中性pH保持，“速效” 胰岛素 ③纯胰岛素（美国） 高纯胰岛素（英国） ：经过凝胶过滤及离子交换层析纯化的胰岛素。 进一步去除了：分子质量相近的胰岛蛋白水解酶；去除了修饰的胰岛素；去除前胰岛素，将制剂中的前胰岛素含量降至10 μg/g以下，即十万分之一以下。 猪胰岛素的酶转化：人胰岛素④ 1982年，在美国、德国、英国与荷兰，通过重组DNA技术生产的人胰岛素首次获得许可应用于临床，它是第一个准许用于人体治疗的重组DNA技术产品。 优点： 供应充分； 消除病原体导致疾病意外传播的危险； 经济实用； 在酵母中，首先表达出一个类似与人胰岛素原的中间产物，然后在酶的作用下，切去连接肽，产生人胰岛素Pry[1]。 (Precursor, recombinant, yeast) [1] Markussen, et al. In peptides, 1986:189-194. 胰岛素的各种制备途径 基因工程胰岛素类似物 ⑥ 胰岛素泵 Little Change In A1c 8.6% in 396 Canadian