新药创制制药技术.ppt

提取工艺 红豆杉树皮，石油醚固-液萃取，碱洗、己烷沉淀、一次层析、一次结晶、溴加成、二次层析和二次结晶。 ★2004年6月28日Bristol-Myers Squibb利用细胞培养生产紫杉醇获得总统绿色化学挑战奖。 半合成工艺 合成侧链，天然提取巴卡亭III 大肠杆菌合成前体药物 紫杉二烯 产量达到1.3g/L, Science, 2010 合成生物学生产紫杉醇的细胞工厂设计 2- synthase 8 – hydroxylase 5 – transferase 2- oxidase 1 - Aminomutase 1 - Co-ligase 19- enzymes from IPP and DMAPP E coli isoprenoid pathway Taxol pathway Glucose Genentech Inc. Genetic Engineering Technology, Inc.,生物技术公司 1976，创建，由风险投资家Robert A. Swanson 和生物化学家 Dr. Herbert Boyer 1973, Boyer 及其同事Stanley Norman Cohen建立重组技术 1977，生产激素hormone somatostatin. 1978，成功合成胰岛素synthetic human insulin. 2008, Genentech employed more than 11,000 people 26 March 2009，Swiss 的Hoffmann-La Roche收购了Genentech，$46.8 billion. Genentech Inc. Genetic Engineering Technology, Inc.,生物技术公司 1976，创建，29岁风险投资家Robert A. Swanson (1947-1999,MIT Chemistry BS/management MS）和生物化学家 Dr. Herbert Boyer (1936-, UCSF) 1973, Boyer，Paul Berg，Stanley Norman Cohen建立重组技术[酶切+连接] 1977，大肠杆菌中表达了激素hormone somatostatin. 1978，成功合成胰岛素synthetic human insulin. 2011, Genentech employed more than 11,000 people 26 March 2009，Swiss 的Hoffmann-La Roche收购了Genentech，$46.8 billion. 1990 April, Boyer and his wife Grace gave the single largest donation (USD $10,000,000) to Yale School of Medicine focused its drug discovery efforts on multiple novel biotherapeutics to market in the areas of oncology, immunology, ophthalmology, and metabolism.? Genentech became the headquarters for all Roche pharmaceutical operations in the United States. 治疗风湿性关节炎 新生血管黄斑病变 转移结/直肠癌，非小细胞肺癌/乳腺癌 非小细胞肺癌/胰腺癌 持续哮喘 急性心肌梗塞 转移性乳腺/胃癌 非霍金奇淋巴瘤 囊性纤维化 重组生长素 慢性肉芽瘤 心肌梗塞/中风 儿童生长素 黑色素瘤 心肌梗塞 Products timeline 1982 - Synthetic human insulin (Humulin) 上市,转让Eli Lilly生产销售, 第一个基因工程药物. 1985 - Protropin (somatrem) – 儿童生长素缺陷辅助治疗 (ceased manufacturing 2004). 1987 - Activase (alteplase) - A recombinant tissue plasminogen activator (tPa) 融栓药心肌梗塞/中风. 1990 - Actimmune (interferon gamma 1b) – 慢性肉芽瘤chronic granulomatous (licensed to Intermune). 1993 - Nutropin (recombinant somatropin) . 1