吴茱萸碱丁酰基衍生物固体脂质纳米粒的体外释放及在体胃肠吸收研究  

In vitro release and in situ gastrointestinal absorption of evodiamine butyryl derivative-loaded solid lipid nanoparticles

作　　者：杨兰 万坤 杨建波 晏声蕾 张奇娆 张景勍 胡雪原 YANG Lan;WAN Kun;YANG Jian-bo;YAN Sheng-lei;ZHANG Qi-rao;ZHANG Jing-qing;HU Xue-yuan(Medicine Engineering Research Center,College of Pharmacy in Chongqing Medical University,Chongqing 400016,China;Dept of Pharmacy,Meishan Cardiovascular and Cerebrovascular Hospital,Meishan Sichuan 620020,China)

机构地区：[1]重庆医科大学药学院重庆高校药物工程研究中心,重庆400016 [2]四川省眉山市心脑血管病医院药剂科,四川眉山620020

出　　处：《中国药理学通报》2018年第5期724-728,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30973645);重庆市研究生科研创新项目资助(No CYS 17172);重庆医科大学大学生科学研究与创新实验项目(No 201724)

摘　　要：目的制备吴茱萸碱丁酰基衍生物(evodiamine butyryl derivative,EBD)和吴茱萸碱丁酰衍生物固体脂质纳米粒(evodiamine butyryl derivative-loaded solid lipid nanoparticles,EBDLN),并研究它们的体外释放特征以及在体胃肠吸收的能力。方法采用一步合成法制备EBD,经薄膜分散法制备EBDLN。采用动态透析法考察EBD和EBDLN的体外释药特征,并用单向灌流法研究吴茱萸碱(evodiamine,EDM)、EBD和EBDLN的胃肠道吸收。结果在同种释放介质中,EBD和EBDLN的释药趋势完全一致,但EBDLN相对于EBD而言其释药速度更慢。EBDLN在各个肠道的K_a值和P_(app)值均明显大于EDM和EBD。且EBDLN在胃、十二指肠、空肠、回肠、结肠中的K_a值分别为EDM的110.14、56.70、51.23、45.70、127.23倍,EBDLN在十二指肠、空肠、回肠、结肠中的P_(app)值分别为EDM的9.74、4.48、3.82、11.30倍。结论EBDLN具有缓释效应,增加了EDM和EBD在胃肠道的吸收。Aim To prepare evodiamine butyryl derivative(EBD)and evodiamine butyryl derivative-loaded solid lipid nanoparticles(EBDLN),and study its release in vitro,and to investigate its in situ gastrointestinal absorption.Methods EBD was prepared by a one-step synthetized method,and then EBDLN was prepared by a film dispersion method.Dynamic dialysis was used to evaluate drug release in vitro,and single-pass gastrointestinal perfusion was employed to study the gastrointestinal absorption of EDM,EBD and EBDLN.Results In identical release media,there were identical drug release tendencies of EBD and EBDLN,but the release rate of EBDLN was faster than EBD.Compared with EDM and EBD,the K a values and P app values of EBDLN in every perfusion segment increased significantly.The K a of EBDLN in stomach,duodenum,jejunum,ileum and colon was 110.14-fold,56.70-fold,51.23-fold,45.70-fold and 127.23-fold of free EDM respectively.The P app value of EBDLN was 9.74-fold,4.48-fold,3.82-fold and 11.3-fold of that of free EDM.Conclusion EBDLN has sustained effect and can enhance the gastrointestinal absorption of EDM and EBD.

关 键 词：吴茱萸碱 吴茱萸碱丁酰衍生物 固体脂质纳米粒 体外释放 在体胃肠吸收 吸收速率常数 表观渗透系数 

分 类 号：R284.1[医药卫生—中药学] R322.44[医药卫生—中医学]