第六章治疗用激素概要课件.pptxVIP

Charpter 6 Incretion applied to treatment Fangzhen Zhou 2011.4 1 What We Will Cover 1 Diabetes and insulin Diabetes and treatment Production of insulin Insulin and insulinR Character of insulin 2 Diabetes and insulin 3 JL on 12/15/22 and 2 mos later Before insulin was discovered in 1921, everyone with type 1 diabetes died within weeks to years of its onset Before Insulin 4 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 5 • 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 Insulin Production Begins • First produced as “Connaught” by the Univ of Toronto 6 Age at start of diabetes 50 30 10 Avg. age of death in 1897 58.0 34.1 11.3 Avg. age of death in 1945 65.9 60.5 45.0 Years Gained 8 26 34 Impact Of Insulin On Life Expectancy By The 1940’s 返回 7 8 9 返回 10 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。 返回11 传统生产工艺：常规胰岛素① [ 除碱性蛋白，结晶 ] 柠檬酸，Zn(Ac)2 ，丙酮，氨水 [ 除酸性蛋白 ] 水、丙酮、氨水 pH4.2~4.3 猪胰岛素生产的工艺路线 12 提取液 碱化液 [ 盐析 ] NaCl pH2~2.5 硫酸 pH3.6~3.8 ，5℃ [ 洗涤，干燥 ] 水、丙酮、乙醚 pH8.0 ，5℃以下，调pH6.0 乙 ，草酸 10~15℃ 胰岛素精品 氨水 pH8~8.4 猪胰脏 去脂溶液 沉淀 滤 液 盐析物 浓缩液 酸化液 结晶 30℃ 以下 [ 浓缩] Zn(Ac)