大黄-黄芪组分自微乳的制备及在体肠吸收特性研究  

Preparation and in-situ intestinal absorption study of Rhei Radix et Rhizoma-Astragali Radix components loaded self-microemulsion

作　　者：侯雨 朱琳 张奇镔 叶小风 柯俏颖 徐志士 魏颖慧[1] HOU Yu;ZHU Lin;ZHANG Qi-bin;YE Xiao-feng;KE Qiao-ying;XU Zhi-shi;WEI Ying-hui(School of Pharmacy,Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学药学院,浙江杭州310053

出　　处：《中草药》2023年第12期3815-3823,共9页Chinese Traditional and Herbal Drugs

基　　金：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)。

摘　　要：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)m V;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(Ka)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 Ka 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.

关 键 词：大黄总蒽醌 黄芪总皂苷 自微乳给药系统 处方研究 伪三元相图 在体肠吸收 

分 类 号：R283.6[医药卫生—中药学]