环孢菌素A柱层析硅胶再生工艺

Study of silica gel regeneration applied on cyclosporine A column chromatography

环孢菌素A工业化生产涉及真菌发酵、萃取、浓缩、结晶、硅胶柱层析、脱色、二次结晶等步骤,目前硅胶柱层析步骤的硅胶只能一次使用,现实生产过程产生了大量的废硅胶,环保处理压力大、企业成本高。据此本文开展了环孢菌素A柱层析硅胶再生工艺研究,针对硅胶上吸附的杂质性质,研究了硅胶再生洗脱溶剂系统,通过响应面法优化再生条件,结果表明:选用含有0.26%聚山梨醇的乙醇反向冲洗4个柱体积,再使用双氧水浓度为0.15%的去离子水正向冲洗2.1个柱体积,冲洗流速为5mL/min;使用压缩空气将再生后的硅胶压出,烘干至水分含量为6%。按照本方法得到的再生硅胶按原工艺使用时,环孢菌素A回收率完全达标,并且可以三次重复使用达标。本研究建立了一套切实可行的环孢素纯化硅胶再生工艺,可有效节约工厂生产成本和减轻环境压力。

The industrial production of cyclosporine A involves fungal fermentation,extraction,concentration,crystallization,silica gel column chromatography,decolorization,secondary crystallization and other steps,among which silica gel column chromatography produces a large amount of waste silica gel,which is under great pressure of environmental protection treatment and high cost for enterprises.Based on this,the silica gel regeneration process of cyclosporine A column chromatography was studied in this paper,and the regeneration conditions were optimized by response surface methodology:four column volumes were backwashed with ethanol containing 0.26%polysorbitol,and 2.1 column volumes were forward washed with deionized water containing 0.15%hydrogen peroxide at a flow rate of 5mL/min.The recycled silica gel was pressed out with compressed air and dried until the moisture content was 6%.The yield of the regenerated silica gel can reach more than 75%when used according to the original process,and the yield of the third regenerated silica gel can still reach 75%.This study established a set of feasible cyclosporine purified silica gel regeneration process,which can effectively save factory production cost and reduce environmental pressure.