【作者】 张斌；

【导师】 王普；

【作者基本信息】 浙江工业大学 ， 制药工程， 2011， 硕士

【摘要】 为提高霉酚酸提取工艺水平,本文首先从霉酚酸与发酵液的理化性质出发,通过将发酵液调节pH10-11,将霉酚酸有效成分释放到滤液中,再采用板框、陶瓷膜、超滤膜、纳滤膜等不同过滤方式的组合试验,对各膜组件进行了筛选,得到了优化的试验方案,筛选出了0.2um的陶瓷膜,截留分子量20000的KJ中空纤维膜和卷式DK纳滤膜,并确立了生产工艺。发酵液经过陶瓷膜过滤进行有效的固液分离,超滤将滤液中的影响结晶的大分子蛋白质和色素等大量杂质进行了有效去除,使结晶效果更好,结晶品质量更高,再进行纳滤浓缩,结晶、精制、烘干,得到霉酚酸成品,经过多批工艺验证,HPLC法检测霉酚酸成品纯度达到99%以上,单个杂质≤0.2%,完全符合药品标准。通过膜工艺的使用,使过滤收率达到85%以上,结晶粗品含量、外观、色泽明显改善,含量从40%提高到85%,霉酚酸提取总收率达到65-70%,生产水平明显提高,生产过程中使用的有机溶剂使用量减少70%,溶剂的损耗减少80%以上。同时生产工艺简化,生产过程更安全、更环保。更多还原

【Abstract】 In order to improve the level of mycophenolic acid extraction process,considering the physical and chemical properties of mycophenolic acid andthe fermentation broth, the broth pH is adjusted to 10-11, and the activeingredients of mycophenolic acid are released into the filtrate. Then acombination of different filtering experiments, such as re-use of frame,ceramic membrane, ultrafiltration membrane, nanofiltration membrane,have been optimized for pilot programs. Finally 0.2um ceramic membrane,20,000 MWCO KJ hollow fiber membrane and DK nanofiltrationmembrane roll are screened out.After ceramic membrane filtration for effective solid-liquid separation,the crystallization of macromolecules such as proteins and pigments largeamounts of impurities are effectively removed by ultrafiltration filtrate, andhigher quality crystal products are obtained. Then through furthernanofiltration concentration, crystallization, refining, drying, the finishedproduct is obtained. Through validation batches, the purity is more than99% and single impurity is less than 0.2% by HPLC, so the progress is infull compliance with pharmaceutical standards.With the membrane technology the filtering yield is more than 85%,and crystallization coarse product content, appearance, colour and lustre are improved obviously, as the content is increased from 40% to 85%. Theextraction total yield is reached to 65-70%. The input organic solvent isreduced by 70%, as well as the wastage of organic solvent is decreased by80%. The method shows great applicable value in the age of policyadvocating conserving the resource, green production, and sustainabledevelopment.更多还原