目的 研究大黄-黄芪多组分自微乳的处方与制备工艺，评价制剂质量，并考察其大鼠肠吸收特性。方法 通过溶解度实验、油相与乳化剂和助乳化剂配伍实验及伪三元相图的绘制，筛选出最优处方组成；并从自微乳的外观、形态、粒径、稳定性等方面对自微乳进行评价。通过大鼠在体单向肠灌流实验考察自微乳的肠吸收特性。结果 自微乳处方中油相为辛酸癸酸单双甘油酯、乳化剂为聚氧乙烯蓖麻油35、助乳化剂为乙二醇。在微乳形成区选择各辅料用量，采用适宜方法加入大黄总蒽醌及黄芪总皂苷制得的组分自微乳，外观均一透明，加水分散后形成黄色乳光的微乳液，透射电镜显微镜（transmission electron microscopy，TEM）下观察到微乳分散均匀，无黏连，呈大小均一圆球形乳滴；平均粒径为（33.01±0.12）nm、多分散指数（polydispersion index，PDI）为0.10±0.02、电位为（−10.10±1.00）mV；自微乳中大黄总蒽醌和黄芪总皂苷质量分数分别为6.29、8.80 mg/g。自微乳中大黄总蒽醌在十二指肠、空肠段的吸收速率常数（K_a）及表观吸收系数（P_app）较回肠段均有显著提高；黄芪总皂苷在小肠吸收良好，各肠段间无显著性差异。结论 筛选出的自微乳处方对大黄-黄芪多组分具有良好的负载性能，乳化效率高；自微乳中大黄总蒽醌及黄芪总皂苷在小肠各段均有良好的吸收，有望改善二者的生物利用度以更好地发挥其协同作用。

Objective The present investigation focused on the formulation, preparation process and intestinal absorption characteristics of Dahuang (Rhei Radix et Rhizoma, RRR)-Huangqi (Astragali Radix, AR) components loaded self-microemulsion. Methods The composition of the formula was screened through the solubility test, compatibility of the oil phase with emulsifier and co-emulsifier, and the quasi-ternary phase diagram. Particle size, polydispersion index (PDI) analysis and transmission electron microscopy (TEM) studies were used to evaluate the prepared self-microemulsion. Intestinal absorption of the microemulsion was characterized using rat single-pass intestinal perfusion technique. Results The optimized emulsion consists of Capmul MCM NF as an oil phase, polyoxyl castor oil EL-35 and ethylene glycol as an emulsifier and co-emulsifier respectively. The droplet size of RRR-AR components loaded microemulsion was (33.01 ±0.12) nm with their PDI (0.10 ±0.02), zeta potential (−10.10 ±1.00) mV. As revealed by the observation under TEM, the microemulsion exhibited homogeneous dispersion and was a spherical emulsion droplet. The content of RRR total anthraquinone and AR total saponins was 6.29 mg/g and 8.80 mg/g, respectively. The microemulsion was stable at room temperature, without stratification or droplet change. The K_a and P_app of RRR total anthraquinone in duodenum and jejunum were significantly higher than those in ileum segments. AR total saponins was well absorbed in all of the small intestine segments. Conclusion A newly developed microemulsion exhibits high emulsification efficiency with high payload of RRR and AR components. The high intestinal absorption of RRR-AR components in all of the small intestine segments was observed by encapsulation in the emulsion, which is expected to improve the oral bioavailability of RRR-AR components.

R283.6

国家自然科学基金资助项目（81873018）；浙江省自然科学基金项目（LY21H280007）