目的 通過星點(diǎn)設(shè)計-效應(yīng)面法優(yōu)化姜黃素- 胡椒堿聚合物復(fù)方膠束（Cur/Pip F127/P123-PM）的處方工藝。方法UPLC法測定姜黃素和胡椒堿的含量。采用薄膜水化法制備Cur/Pip F127/P123-PM，在單因素實驗的基礎(chǔ)上，以投藥量、F127所占質(zhì)量比和水化體積為自變量，以姜黃素載藥量和包封率、胡椒堿包封率以及膠束粒徑為因變量，進(jìn)行3因素5水平的星點(diǎn)-設(shè)計效應(yīng)面法實驗，分析結(jié)果得出最優(yōu)處方并對其進(jìn)行驗證。最后對膠束制劑的最佳凍干條件進(jìn)行初步篩選。結(jié)果 優(yōu)化得到的Cur/Pip F127/P123-PM最佳處方工藝：姜黃素與胡椒堿的投藥量分別為12.96 mg和0.69 mg、F127的質(zhì)量比為0.46、水化體積為8.85 mL。采用最優(yōu)處方制得的復(fù)方姜黃素膠束制劑對姜黃素的載藥量為5.63%、溶解度為1.27 mg/mL、包封率為86.86%；對胡椒堿的包封率為77.54%；膠束制劑平均粒徑為66.79 nm；Zeta電位接近于0。以8%甘露醇為保護(hù)劑制得的凍干制劑復(fù)溶效果較好。結(jié)論 星點(diǎn)設(shè)計-效應(yīng)面法所建立的模型能較好地用于復(fù)方姜黃素膠束制劑的處方優(yōu)化，精度高，預(yù)測性好。

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.

國家自然科學(xué)基金項目（81274005）；河北省研究生創(chuàng)新項目（CXZZSS2019149）；河北省中醫(yī)藥管理局項目（2017212）