目的 星点设计-效应面法优化银杏酮酯(GBE50)的β-环糊精(β-CD)包合物的制备工艺。方法 以饱和水溶液法制备GBE50-β-CD包合物,采用星点设计优化制备工艺,以β-CD与GBE50的投料质量比、包合时间和包合温度为自变量,包合率为因变量,分别进行多元线性回归和二项式方程拟合,并根据最佳数学模型描绘效应面,选择最佳处方工艺进行验证试验。结果 二项式方程拟合度较高,预测性好,r=0.966;效应面法优选出的最佳工艺条件为β-CD与GBE50的投料质量比3∶1,包合时间6 h,包合温度60℃。最佳工艺验证试验结果与二项式拟合方程预测值偏差为1.07%。结论 应用星点设计-效应面优化法能够精确有效地优化GBE50-β-CD包合物的制备工艺,优选出的最佳工艺稳定可行,可用于工业生产。

Objective To optimize the preparation of Ginkgo biloba extract-β-cyclodextrin inclusion (GBE50-β-CD inclusion) complex by central composite design and response surface methodology. Methods Saturated aqueous solution method was used to prepare GBE50-β-CD inclusion complex. The preparation was optimized by central composite design. With the mass ratio of β-CD/ GBE50, inclusion time and temperature as the independent variables and with the inclusion rate as the dependent variable, the binomial and linear equations were fitted to the data of overall desirabilities, and the resulting equation was used to produce 3-D response surface graphs, through which optimal formulation was predicted, the best prescription process was chosen to verification test. Results It showed that the correlation coefficient of second-order quadratic model was higher and the prediction was better (r = 0.966); The optimum conditions for the preparation of GBE50-β-CD inclusion complex were as follows: the mass ratio of β-CD/GBE50 3:1, inclusion time 6 h, inclusion temperature at 60 ℃. The deviation between the result of the best craft verification test and the binomial fitting equation forecast value is 1.07%. Conclusion Central composite design and response surface methodology is successfully used to optimize the preparation of GBE50-β-CD inclusion complex. The optimized process is reliable, stable, and available for the industrial production.

“十二五”重大新药创制科技重大专项项目(2011ZX09201-101-19);国家科技部支撑项目(2007BAI41B00,2007BAI41B01);天津市科技支撑项目(09ZCKFSH01200)