东莨菪内酯胶束的大鼠在体胃肠吸收动力学研究  

Gastrointestinal Absorption Kinetics of Scopoletin Micelles in Rats

作　　者：马宇 杨证玉 何宝红 毛家敏 曾迎春 Ma Yu;Yang Zhengyu;He Baohong;Mao Jiamin;Zhen Yingchun(School of Pharmacy, Chengdu Medical College, Chengdu 610500, China;Key Laboratory of Structure Specific Small Molecule Drugs of Universities in Sichuan Province, Chengdu Medical College, Chengdu 610500, China)

机构地区：[1]成都医学院药学院,成都610500 [2]成都医学院结构特异性小分子药物研究四川省高校重点实验室,成都610500

出　　处：《成都医学院学报》2022年第3期306-310,共5页Journal of Chengdu Medical College

基　　金：四川省科技厅面上项目(No:2019YJ0372);四川省大学生创新创业训练项目(No:S202013705003)。

摘　　要：目的建立测定在体胃肠样品中东莨菪内酯(Sco)含量的分析方法,考察包载Sco的聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇(Soluplus)胶束给药系统(Sco-Ms)的大鼠在体胃肠吸收动力学。方法采用高效液相色谱(HPLC)法,测定Sco在大鼠胃肠黏膜匀浆液中的稳定性;通过大鼠在体原位胃灌注模型以及在体单向肠灌流模型,考察Sco-Ms的胃肠吸收情况。结果Sco在0.51~203.20 mg/L内线性良好;与各胃肠黏膜匀浆液孵育2 h后,Sco药物浓度的减少比例均在5%以内;在胃中灌注2 h后,Sco和Sco-Ms的胃吸收百分率比较差异无统计学意义(P>0.05);与Sco比较,Sco-Ms在十二指肠、空肠、回肠和结肠4个肠段中的表观渗透系数P_(app)和吸收速率常数K_(a)均明显增加(P<0.05)。结论Sco在胃肠道黏膜中较为稳定,Sco-Ms胶束系统能有效促进Sco在整个肠段的吸收,进而提高Sco的口服生物利用度。Objective To develop an analytical method for the quantification of scopoletin(Sco)in the gastrointestinal samples in vivo and investigate the gastrointestinal absorption kinetics of polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol(soluplus)based Sco micelles(Sco-Ms)drug delivery system in rats.Methods A high performance liquid chromatography(HPLC)method was developed for the quantification of Sco.Then,the stability of Sco in homogenate from the gastrointestinal mucosa of rats was determined.Meanwhile,in-situ gastric perfusion model and single-pass intestinal perfusion model in rats were used to investigate the gastrointestinal absorption of Sco-Ms.Results This method was proven to be linear over the concentration range of 0.51-203.20 mg/L.After 2 h incubation with homogenate,the reduction of drug concentration was within 5%.After perfusion for 2 h in the stomach,there was no significant difference in the absorption rate between Sco and Sco-Ms(P>0.05).Compared with Sco,the apparent permeability coefficient(P_(app))and the absorption rate constant(K_(a))value of Sco-Ms in the duodenum,jejunum,ileum and colon were all increased significantly(P<0.05).Conclusion Sco has good stability in the gastrointestinal mucosa.Sco-Ms can effectively promote the absorption of Sco in the whole intestine,thereby improving the oral bioavailability of Sco.

关 键 词：东莨菪内酯 聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇 胶束 稳定性 胃肠吸收 

分 类 号：R285.5[医药卫生—中药学]