利用綠色化學製備選擇性雌激素受體調節劑系列藥物技術開發

ASIA unversity > 醫學暨健康學院 > 食品營養與保健生技學系 > 科技部研究計畫 > Item 310904400/9419

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题名:	利用綠色化學製備選擇性雌激素受體調節劑系列藥物技術開發
作者:	李傳珍
贡献者:	健康學院保健營養生技學系
日期:	2009
上传时间:	2010-05-07 03:38:06 (UTC+0)
摘要:	綠色化學的技術是以污染性低的清潔生產，使用對人類健康及環境危害較小的溶劑、避免及減少廢棄物逸散，且比現有化學藥品的毒性更低，或意外發生時更安全化學藥品的使用與設計。綠色化學使用污染性低的反應條件，能減少設備體積與產能的比值，能源的消耗，廢棄物的排放，最終生產廉價的產品。所以產業如何提高生產品質與降低製造成本與符合環保要求是一重要課題。選擇性雌激素受體調節劑(Selective Estrogen Receptor Modulators，SERMs)是種多功能的藥物，其具有系列結構各異的化合物，能與雌激素受體結合，依據靶組織和激素的內環境不同，表現出雌激素激動劑或雌激素拮抗劑 (Antiestrogens) 的作用，可用於治療停經婦女與雌激素不足有關的一系列疾病。雷洛昔芬 (raloxifene）系列藥物具有停經後婦女骨質疏鬆症之預防及治療。本計畫將利用微反應器與微混合器製備選擇性雌激素受體調節劑雷洛昔芬 (raloxifene）系列藥物，改變製備中的反應溫度、反應物流速、反應物滯留時間、離子溶劑種類、反應物濃度、反應壓力、製造過程中的原料藥以高效能液相層析儀(HPLC)、質譜儀(MS)、核磁共振光譜儀(NMR)進行主產物分析並判斷可能之不純物含量與種類。亦擬探討系列的微反應系統參數變化之行為，以提供程序設計及最適化之參考。利用微反應器技術將可減少使用溶劑並降低高耗熱能，在環保與製藥工業中將可永續發展。 Green Chemistry is diffusing throughout the chemical industry and includes use and development of new substances and processes. Green Chemistry intends to eliminate intrinsic hazard itself, rather than focusing on reducing risk by minimizing exposure. Much of the chemical industry is capital-intensive, based on economies of scale, and thus large companies are typically slow to convert to new technologies. Estrogen receptor and endogenous estrogens play important roles in the development and function of female reproductive system. Selective estrogen receptor modulators (SERMs) which fully antagonize the effects of estrogen on uterine and mammary tissues, while mimicking the effects of estrogen on the bone and cardiovascular system have been investigated as a possible alternative to estrogen replacement therapy. Raloxifene has been treating for prevention of breast cancer and prevention of osteoporosis. In this proposal will development green chemistry method applies in synthesis series of SERMs. Using microreactor technology that small-scale commercial applications, reducing waste, include safety, potential performance enhancement, and environmental impact. The experiments will designed to use mix level orthogonal array to find optimized operation factors. Several parameters will studied and optimized, such as time of reaction, reaction temperature, reactant flow, kinds of ionic liquid. The products of detection also will be determined with chromatography and spectroscopy. If the proposal execute successfully will be carry out active pharmaceutical industry promote to manufacture, increase efficiency and prevent waste.
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