目的 采用Box-Behnken响应面法优化白藜芦醇（resveratrol）-辛酸癸酸聚乙二醇甘油酯（Labrasol）/泊洛沙姆407（P407）混合胶束（Res-Labrasol/P407-MM）的处方工艺，并考察其体外特征。方法 HPLC法测定白藜芦醇含量。薄膜分散-探头超声法制备Res-Labrasol/P407-MM。在单因素实验结果的基础上，以投药量、水化体积和水化温度为考察因素，胶束样品的质量浓度和药物沉降率为评价指标，采用Box-Behnken响应面法优化处方，并对最优处方制备的胶束进行外观形态、粒径和体外释放行为评价。结果 最佳处方工艺为白藜芦醇投药量28 mg，水化体积9 mL，水化温度40℃，在此条件下测得白藜芦醇平均载药量为（11.62±0.20）%、平均包封率为（93.96±1.83）%、胶束平均粒径为（69.00±1.58） nm，平均Zeta电位为（-21.25±0.18） mV。样品质量浓度和沉降率的实测值与预测值偏差较小，RSD<5.5%。结论 Box-Behnken响应面法预测性良好，可以用于优化Res-Labrasol/P407-MM的处方工艺。制备的混合胶束包封率高，粒径小，分布均匀，缓释效果明显。

Objective To optimize the prescription process of resveratrol-Labrasol/P407 mixed micelles (Res-Labrasol/P407-MM) by Box-Behnken response surface method. The characteristics of micelles in vitro were investigated. Methods The content of resveratrol was determined by HPLC. Res-Labrasol/P407-MM was prepared by thin film dispersion-probe ultrasonic method. Based on the results of single factor experiment, Box-Behnken response surface method was used to optimize the formulation, with the dosage, hydration volume, hydration temperature as the factors, and the concentration of micelles sample and drug sedimentation rate as the evaluation indexes. The morphology, particle size and in vitro release behavior of the micelles prepared by the optimal formulation were evaluated. Results The optimal formulation process was as follow:the dosage of resveratrol was 28 mg, the hydration volume was 9 mL, and the hydration temperature was 40℃. Res-Labrasol/P407-MM prepared by the optimum formulation had the average drug loading of (11.62 ±0.20)%, and the average encapsulation efficiency of (93.96 ±1.83)%. The average particle size and Zeta potential of micelles was (69.00 ±1.58) nm and (−21.25 ±0.18) mV, respectively. RSD of measured and predicted values of sample concentration and settlement rate were less than 5.5%. Conclusion Box-Behnken response surface method has good predictability and can be used to optimize the formulation of Res-Labrasol/P407-MM. Mixed micelles have high encapsulation efficiency, small particle size, uniform distribution and obvious slow release effect.

R283.6

国家自然科学基金资助项目（81803740）；河南省高等学校重点科研项目（18A350007）