目的 通过星点设计-效应面法优化姜黄素- 胡椒碱聚合物复方胶束（Cur/Pip F127/P123-PM）的处方工艺。方法UPLC法测定姜黄素和胡椒碱的含量。采用薄膜水化法制备Cur/Pip F127/P123-PM，在单因素实验的基础上，以投药量、F127所占质量比和水化体积为自变量，以姜黄素载药量和包封率、胡椒碱包封率以及胶束粒径为因变量，进行3因素5水平的星点-设计效应面法实验，分析结果得出最优处方并对其进行验证。最后对胶束制剂的最佳冻干条件进行初步筛选。结果 优化得到的Cur/Pip F127/P123-PM最佳处方工艺：姜黄素与胡椒碱的投药量分别为12.96 mg和0.69 mg、F127的质量比为0.46、水化体积为8.85 mL。采用最优处方制得的复方姜黄素胶束制剂对姜黄素的载药量为5.63%、溶解度为1.27 mg/mL、包封率为86.86%；对胡椒碱的包封率为77.54%；胶束制剂平均粒径为66.79 nm；Zeta电位接近于0。以8%甘露醇为保护剂制得的冻干制剂复溶效果较好。结论 星点设计-效应面法所建立的模型能较好地用于复方姜黄素胶束制剂的处方优化，精度高，预测性好。

Objective To optimize the prescription process of curcumin-piperine polymeric compound micelles (Cur/Pip F127/P123-PM) by central composite design-response surface method. Methods The content of curcumin and piperine was determined by UPLC. The Cur/Pip F127/P123-PM was prepared by thin film hydration method. Based on the single factor test, the dosage, the mass ratio of F127 and the volume of water were used as independent variables, and the drug loading and entrapment efficiency of curcumin, entrapment efficiency of piperine and the micelle size were dependent variables, and next central composite design-response surface method of three factors and five levels was carried out. The analysis results showed and verified the optimal prescription. Finally, the optimal lyophilization conditions of the micelle preparation were initially screened. Results The optimal preparation process was as follow:the dosage of curcumin and piperine was 12.96 mg and 0.69 mg, respectively; The mass ratio of F127 was 0.46, and the volume of water was 8.85 mL. The compound curcumin micelles prepared by the optimum formulation had the loading capacity of 5.63%, solubility of 1.27 mg/mL and entrapment rate of curcumin was 86.86%. The entrapment rate of piperine was 77.54%; The micelle size was 66.79 nm and the Zeta potential was close to zero. The lyophilized products prepared by using 8% mannitol as a protective agent had a good redispersion. Conclusion The model established by central composite design-response surface method can be used to optimize the prescription of compound curcumin micelles, and the method had a high accuracy and good predictability advantage.

国家自然科学基金项目（81274005）；河北省研究生创新项目（CXZZSS2019149）；河北省中医药管理局项目（2017212）