胆碱类离子液体促进槲皮素口服吸收的考察  

Investigation on Promoting Oral Absorption of Quercetin by Choline-based Ionic Liquids

作　　者：宣婧婧 武喜营 戚建平[3] 庄婕 XUAN Jingjing;WU Xiying;QI Jianping;ZHUANG Jie(School of Pharmacy,Shanghai University of Medicine and Health Sciences,Shanghai 201318;Shanghai Dermatology Hospital,Shanghai 200443;School of Pharmacy,Fudan University,Shanghai 201203)

机构地区：[1]上海健康医学院药学院,上海201318 [2]上海皮肤病医院,上海200443 [3]复旦大学药学院,上海201203

出　　处：《中国医药工业杂志》2024年第6期811-819,共9页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金青年项目(82003703)。

摘　　要：该研究旨在利用胆碱类离子液体(ILs)促进难溶性天然成分槲皮素(1)的口服吸收。首先,合成并表征氢氧化胆碱(Ch)与6种酸[苯丙氨酸(Phe)、香叶酸(Ger)、丙二酸(Mal)、山梨酸(Sorb)、琥珀酸(Suc)和苹果酸(Mala)]构成的ILs。根据各ILs中1的溶解度,筛选出对1增溶效果较佳的ILs为香叶酸胆碱([Ch][Ger])和山梨酸胆碱([Ch][Sorb])。考察了2种体系(1-[Ch][Ger]和1-[Ch][Sorb])的体外溶出特性和在SD大鼠体内的药动学行为。结果显示,[Ch][Ger]和[Ch][Sorb]均能明显提高1的体外溶出速度,但后者在20 min时的溶出率与1原料药相似。以1混悬剂为对照,1-[Ch][Ger]、1-[Ch][Sorb]的相对生物利用度分别为588.0%和501.9%。本研究对难溶性天然成分的口服制剂研究有一定的参考意义。The aim of this study was to promote the oral absorption of quercetin(1),an insoluble natural component,using choline-based ionic liquids(ILs).Firstly,a series of ILs composed of choline hydroxide(Ch)and various acids[phenylalanine(Phe),geranic acid(Ger),malonic acid(Mal),sorbic acid(Sorb),succinic acid(Suc)and malic acid(Mala)] were synthesized and characterized extensively.According to the solubility of 1 in various ILs,the ILs with the superior solubilization effects on 1 were screened out,which were choline geranate([Ch][Ger])and choline sorbate([Ch][Sorb]).Then,the in vitro dissolution characteristics and in vivo pharmacokinetic behaviors in SD rats of the above two systems(1-[Ch][Ger]and 1-[Ch][Sorb])were investigated.The results showed that both 1-[Ch][Ger]and 1-[Ch][Sorb]significantly improved the in vitro dissolution rate of 1,but the dissolution rate of the latter at 20 min was similar to that of 1 bulk drug.With 1 suspension as the control,the relative bioavailabilities of 1-[Ch][Ger]and 1-[Ch][Sorb]were 588.0%and 501.9%,respectively.This study is of instructive significance for the investigation of oral preparations of insoluble natural ingredients.

关 键 词：离子液体 槲皮素 溶解度 口服吸收 药物动力学 

分 类 号：R944.9[医药卫生—药剂学] R283[医药卫生—药学]