目的 鉴于葛根黄酮类成分间溶解性与渗透性的自调节作用，以泊洛沙姆407（Pluronic F127，F127）和15-羟基硬脂酸聚乙二醇脂（Solutol HS15）为载体材料制备共载葛根素与大豆苷元的聚合物混合胶束（puerarin and daidzein co-delivery polymer mixed micelles，PD-FS/PMMs）及其冻干粉，以实现同源成分共载。方法 采用薄膜水化法制备PD-FS/PMMs，以胶束稳定性为考察指标进行了处方工艺优化；应用核磁共振氢谱、透射电子显微镜与激光粒度仪等对其进行物理性能表征，并通过体外透析法考察药物释放情况。为了进一步提升胶束相关口服制剂的成型性，还对胶束溶液进行了冻干处理并基于外观与复溶效果考察了冻干保护剂的种类与用量，同时开展了冻干粉的性能表征研究。结果 成功制备了PD-FS/PMMs，最佳处方为葛根素与大豆苷元的投药量分别为80.98、3.46 mg，载体总量为200 mg，其中，F127质量分数为77.30%；制备的胶束外观圆整，粒度均匀，粒径为18~20 nm，且2种成分的体外释放互不影响；确定了胶束溶液的最佳冻干工艺是以40 mg/mL甘氨酸作为冻干保护剂，冻干粉形态以片状为主且复溶效果好。结论 研究不仅解决了不同疏水性成分共载的难题，且实现了同源成分共载胶束的制备，为后期开展葛根素口服降压制剂的体内研究与临床开发奠定基础，并为旨在高生物利用度的共载制剂体系的设计提供共载成分筛选的新思路。

Objective Based on the self-regulatory effect of solubility and permeability between the flavonoid components of Gegen (Pueraria lobata) found in the previous study, Pluronic F127 (F127) and Solutol HS15 were used as carrier materials to prepare polymer mixed micelles of puerarin and daidzein co-delivery (PD-FS/PMMs) and their lyophilized powder to achieve co-loading of homologous components. Methods In this study, PD-FS/PMMs were prepared by thin film hydration, and the stability of PD-FS/PMMs was used as an indicator for the optimization of the prescription process. Proton nuclear magnetic resonance, transmission electron microscopy and laser particle size measurement were applied to characterize the physical properties of PD-FS/PMMs, and the release of the drug was investigated by in vitro dialysis. To further enhance the formability of PD-FS/PMMs-related oral formulations, PD-FS/PMMs were lyophilized and the type and dosage of lyoprotectant were investigated based on the appearance and re-solubilization effect of PD-FS/PMMs, and a performance characterization study of the lyophilized powder was carried out. Results The results showed that PD-FS/PMMs were successfully prepared with an optimal prescription of 80.98 mg puerarin, 3.46 mg daidzein and 200 mg carrier, of which F127 accounted for 77.30% of the carrier. The PD-FS/PMMs were prepared with a rounded appearance and uniform particle size of 18-20 nm, and the in vitro release of the two components did not affect each other. The optimal lyophilisation process for PD-FS/PMMs was determined to be 40 mg/mL glycine as a lyophilisation protectant, with the lyophilised powder form being predominantly flake and with good re-solubilisation. Conclusion The study not only solved the problem of co-loading of different hydrophobic components, but also achieved the preparation of co-delivery micelles of homologous components, and laid the foundation for later in vivo studies and clinical development of oral antihypertensive formulations of puerarin, and provided a new idea of co-delivery component screening for the design of co-delivery formulation systems aiming to improve the low bioavailability.

R283.6

国家重点研发计划项目（2017YFC1702904）；江西省自然科学基金项目（20212BAB216013）