AEE在人工胃/肠液和肠道菌群及生物样品中的稳定性  

Stability of aspirin eugenol ester in the artificial stomach/intestinal fluid,intestinal flora and biological samples

作　　者：陶琦 秦哲[1] 白莉霞 刘希望[1] 李世宏[1] 杨亚军[1] 李剑勇[1] TAO Qi;QIN Zhe;BAI Lixia;LIU Xiwang;LI Shihong;YANG Yajun;LI Jianyong(Key Laboratory of New Animal Drug Project of Gansu Province,Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs,Lanzhou Institute of Husbandry and Pharmaceutical Sciences,Chinese Academy of Agricultural Sciences,Lanzhou 730050,China)

机构地区：[1]中国农业科学院兰州畜牧与兽药研究所农业农村部兽用药物创制重点实验室/甘肃省新兽药工程重点实验室,甘肃兰州730050

出　　处：《中国兽医学报》2021年第10期2021-2026,共6页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(31972739,31872518)。

摘　　要：考察阿司匹林丁香酚酯(AEE)在人工胃/肠液和肠道菌群及生物样品中的稳定性,为开发AEE口服制剂提供理论基础。采用高效液相色谱法(HPLC)分别检测AEE在空白人工胃液(pH1.3,不含酶)、空白人工肠液(pH6.8,不含酶)、人工胃液(pH1.3,含胃蛋白酶)、人工肠液(pH6.8,含胰蛋白酶)中孵育0.0,0.5,1.0,2.0,3.0,4.0,5.0,6.0 h的含量变化;分别检测AEE与SD大鼠(雄性)肠道菌群共孵育0.0,2.0,4.0,6.0,8.0,10.0,12.0 h,在生物样品中孵育0.0,0.5,1.0,2.0,3.0,4.0,5.0,6.0 h的含量变化。结果表明,AEE在空白人工胃液中孵育0~2 h剩余百分比基本没有发生变化,之后随着时间的增加,剩余百分比有明显地下降,孵育6.0 h后下降到71%;在人工胃液中的剩余百分比随着时间的增加而下降,从0 h的98%到6 h的65%;在空白人工肠液中孵育,剩余百分比随着时间延长,逐渐下降,从0 h的98%到6 h的75%;在人工肠液中孵育0~1 h,稍微下降,但孵育1~3 h,剩余百分比迅速从77%下降到22%,孵育到5 h时,剩余百分比降为0%;AEE在SD大鼠肠道菌群中孵育时发生了降解,随着时间的延长,AEE的剩余百分比逐渐下降,生成的两种主要代谢产物为水杨酸和丁香酚;而AEE在肝、胃、大肠、小肠等生物样品中发生明显降解,直接生成的两种主要代谢产物为水杨酸和丁香酚。综上所述,AEE在空白胃液、人工胃液、空白人工肠液有一定程度的降解,但在人工肠液、生物样品和SD大鼠肠道菌群中可以发生明显的降解。The aim of this study is to provide a theoretical basis for aspirin eugenol ester(AEE)in the development of oral preparations by investigating the stability of AEE in the artificial stomach/intestinal fluid,intestinal flora,and biological samples.High performance liquid chromatography(HPLC)was used to measure the changes of AEE content after 0.0,0.5,1.0,2.0,3.0,4.0,5.0,6.0 h incubation in blank artificial gastric juice(pH=1.3,without enzyme),blank artificial intestinal juice(pH=6.8,without enzyme),artificial gastric juice(pH=1.3,with pepsin),artificial intestinal fluid(pH=6.8,with trypsin),and to measure the changes of AEE content after co-incubation with intestinal flora of SD rats(male)for 0.0,2.0,4.0,6.0,8.0,10.0,12.0 h and biological samples for 0.0,0.5,1.0,2.0,3.0,4.0,5.0,6.0 h,respectively.The results showed that the remaining percentage of AEE in blank artificial gastric juice did not change from o h to 2 h,and then decreased significantly to 71%at 6.0 h;the remaining percentage in artificial gastric juice decreased with time,from 98%at 0 hto 65%at 6 h;the remaining percentage of AEE in blank artificial intestinal fluid decreased gradually with time,from 98%at 0 hto 75%at 6 h;AEE in artificial intestinal fluid decreased slightly for 0 to 1 h,however,the remaining percentage decreased rapidly from 1 hto3 h,from 77%to 22%and decreased to 0%at 5 h;degradation of AEE occurred during incubation in the intestinal flora of SD rats,the remaining percentage of AEE decreased over time,and the two main metabolites generated were salicylic acid and eugenol;AEE was significantly degraded to the same two main metabolites in liver,stomach,large intestine,small intestine and other biological samples as in intestinal flora of SD rats.In conclusion,AEE can be degraded to some extent in blank gastric juice,artificial gastric juice and blank artificial intestinal juice,but it can be significantly degraded in artificial intestinal juice,biological samples and intestinal microflora of SD rats.

关 键 词：阿司匹林丁香酚酯(AEE) 肠道菌群 生物样品 人工胃液 人工肠液 稳定性 

分 类 号：S859.79[农业科学—临床兽医学]