环孢菌素A结晶工艺的优化

为了确定环孢菌素A结晶工艺，对溶剂种类、反溶剂加入量、结晶温度和降温方式等因素的影响进行研究。首先通过静态结晶研究，确定了丙酮／水结晶体系和溶剂比例。在此基础上，设计了正交试验L9（34）考察动态结晶中各因素对环孢菌素A结晶收率和纯度的影响，并进一步优化了结晶降温方式。结果表明：确定环孢菌素A结晶的最佳条件为采用梯度程序降温，养晶温度为-5℃，丙酮和水的体积比为2：1，反溶剂水流加时间为0．5h，开始流加点为降温至0℃，结晶时间约为3h。经HPLC分析环孢菌素A的纯度平均值为99．15％，收率平均值为87．7％。

Optimization of crystal process of cyclosrporine A

The crystalization technology of cyclosporine A was studied by using single factor test and or- thogonal experiment design. Effects of different solvents, solvent ratio, and temperature on the crystalli- zation were investigated. Results revealed that the water content had important effects on the purity and recovery of cyclosporine A and crystallization temperature was also another important factor. The optimum crystalization conditions of cyclosporine A were determined as follows： the cooling in gradient was applied; crystal temperature was -5 ℃ ; solvent ration was 2：1 （acetone： water）, feeding time of water was 30 rain; and crystallization period was 3 h. The average HPLC purity of cyclosporine A reached 99. 15%. The average crystalline recovery was 87.7%.