5-氟尿嘧啶口服微乳的制备及其大鼠肠吸收作用研究.pdfVIP

5一氟尿嘧啶口服微乳的制备及其大鼠肠吸收作用研究 李文浩 ，何 应 (天津大学药物科学与技术学院，天津市 300072) 中图分类号 R979．1；R965 文献标识码 A 文章编号 1001—0408(2008)07—0501—03 摘 要 目的：制备5一氟尿嘧啶(5一Fu)口服微乳，并考察其在大鼠肠吸收的作用。方法：以肉豆蔻酸异丙酯为油相、单辛／癸酸甘 油酯为乳化剂，借助伪三元相图法对不同5一Fu微乳处方进行评价；用外翻肠囊法制备肠吸收离体模型，考察5一Fu微乳的吸收 部位和促吸收效果。结果：选择肉豆蔻酸异丙酯一单辛／癸酸甘油酯一无水乙醇一水(Km=1：2)体系作为5一Fu微乳的载药体 系；与其溶液比较，5一Fu微乳可明显改善药物的肠吸收，小肠中后段是其最佳吸收部位，90min时累积吸收率微乳是溶液的3 倍。结论：所制备的5一Fu微乳性质稳定、肠吸收效果良好。 关键词 5一氟尿嘧啶；微乳；伪三元相图；肠吸收 Preparation and Intestinal Absorption Effect of 5—‘Fluorouracil Microemulsion in Rats LI Wen—hao，HE Ying(College of Pharmaceutical Sciences and Technology，Tianjin University，Tianjin 300072，China) ABSTRACT OBJECTIVE：To prepare 5一fluorouracil(5一Fu)microemulsion and to investigate the intestinal absorption of 5一Fu microemulsion in rats、METHODS：The formulation of 5一Fu microemulsion was optimzied using pseudo—ternary phase diagrams with isopropyl myristate(IPM)as oil phase and ODO—L as surfactant；the intestinal absorption ex vivo model was prepared using everted intestinal sac method to investigate the absorption sites and absorption efficiency of 5一Fu mi— croemulsion in rats．RESULTS：IPM／ODO—L／Et0H／H 0 (Km=1：2)was selected as the delivery system of 5一Fu；as compared with 5一Fu solution．the intestinal absorption of 5一Fu microemulsion was significantly improved and the middle and lower segments of rat’S intestine were the best sbsorption sites for 5一Fu microemulsion and the accumulative aborption rates of 5一Fu microemulsion at 90 min was 3一fold that of 5一Fu solution．CONCLUSION：The prepared 5一Fu microemulsion iS stable in quality and well—absorbed in rats’intestine． KEY WORDS 5一Fluorouracil；Microemulsion；Pseudo—ternary phase diagram：Intestinal absorption 5～氟尿嘧啶(5一Fu)为嘧啶类的氟化物，是临床常用的 (IPM)、单辛／癸酸甘油酯(ODO—L)均由广州慧源绿色化工 抗癌药物之一。由于5一Fu脂溶性差，胃肠道吸收不完全，因此 有限公司提供；Kreb—Ringer’S营养液(每1 000 mL蒸馏水 临床上多采用静脉推注或静脉滴注方式给药，但由于该药物毒 中含有氯化钠7．4 g、氯化钾0．35 g、碳酸氢钠1．37 g、磷酸二 性大，常常引起严重的不良反应[】I。口服微乳能够促进