广藿香油肠溶滴丸制备及其对溃疡性结肠炎大鼠的药效评价  

Preparation of Patchouli Oil Enteric-coated Dropping Pills and Its Efficacy Evaluation on Ulcerative Colitis Rats

作　　者：李晓锋 陈卫东 陈华源 许玮华 刘二刚 申欢 王冰 黄永焯 LI Xiaofeng;CHEN Weidong;CHEN Huayuan;XU Weihua;LIU Ergang;SHEN Huan;WANG Bing;HUANG Yongzhuo(School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230031,China;Zhongshan Institute for Drug Discovery,Zhongshan 528400,China;Shanghai Institute of Materia Medica Chinese Academy of Sciences,Shanghai 201203,China;Nantong Haimen Yangtze Delta Drug Advanced Research Institute,Nantong 226133,China)

机构地区：[1]安徽中医药大学药学院,合肥230031 [2]中科中山药物创新研究院,广东中山528400 [3]中国科学院上海药物研究所,上海201203 [4]南通市海门长三角药物高等研究院,江苏南通226133

出　　处：《中国现代应用药学》2024年第12期1621-1630,共10页Chinese Journal of Modern Applied Pharmacy

基　　金：中国科学院药物创新研究院自主部署项目(CASIMM0120184002);上海市科委自然基金项目(21ZR1475200);中山市引进科研创新团队项目(CXTD2022011);中山市第一批科技创新领军人才资助项目(LJ2021001)。

摘　　要：目的 制备广藿香油肠溶滴丸,评价其结肠靶向释放性能,并验证其对大鼠溃疡性结肠炎(ulcerative colitis,UC)的治疗作用。方法 单因素结合响应面优化法筛选基质种类及优化制备工艺参数;以体外溶出度为指标,筛选和确定Eudragit包衣处方和包衣厚度;以大鼠为模型,考察制剂经口服后的结肠靶向释放性能,以及对2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)诱导的大鼠UC模型的治疗作用。结果 广藿香油滴丸的最优处方为广藿香油∶PEG6000∶PEG8000比例1∶1∶1;最优工艺为滴速33滴·min^(-1)、管口温度9℃、滴距6 cm;包衣最优处方为Eudragit L100∶Eudragit S100比例3∶7。与广藿香油相比,广藿香油肠溶滴丸组明显改善了大鼠体质量减轻、便血和结肠缩短等病理症状,使血清中促炎细胞因子IL-6、IL-1β和IL-23表达显著下调及抗炎细胞因子IL-10、TGF-β1表达显著上调,结肠组织中黏蛋白Mucin-1、Mucin-2的mRNA表达显著上调及炎症细胞因子IL-6、IL-1β、TNF-α的mRNA表达显著下调。结论 广藿香油肠溶滴丸具有结肠靶向释放能力,并提高了药物的抗炎效果。OBJECTIVE To prepare patchouli oil enteric-coated dropping pills,evaluate its colon-targeted release behaviors and therapeutic potency against rat ulcerative colitis(UC).METHODS The single factor combined with response surface optimization method was used to screen matrix types and optimize preparation process parameters.Formula and thickness of Eudragit coating was selected based on dissolution tendency toward simulated intestinal fluids.Finally,colon targeting release behavior and the therapeutic effect of the preparation were assessed on the rat UC model induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS).RESULTS The optimal prescription of patchouli oil dropping pills was patchouli oil∶PEG6000∶PEG8000 ratio of 1∶1∶1;and the optimal condition for preparing patchouli oil pills was keeping nozzle temperature at 9℃,and dropping pills at the speed of 33 drops·min^(−1),with dropping distance set at 6 cm;the optimal ratio of Eudragit L100∶Eudragit S100 was 3∶7 for preferential release in simulate intestinal fluid over simulated gastric fluid.Compared with free patchouli oil,patchouli oil entericcoated dropping pills significantly alleviated the pathological symptoms such as weight loss,hematochezia and colon shortening in rats;the expression of pro-inflammatory cytokines IL-6,IL-1β,and IL-23 in serum was significantly down-regulated and the expression of anti-inflammatory cytokines IL-10 and TGF-β1 was significantly up-regulated.The mRNA expression of Mucin-1 and Mucin-2 in colon tissue was significantly up-regulated and the mRNA expression of inflammatory cytokines IL-6,IL-1β,and TNF-αwas significantly down-regulated.CONCLUSION The patchouli oil enteric-coated dropping pills have colon-targeted release ability and improve the anti-inflammatory effect of drugs.

关 键 词：广藿香油 肠溶滴丸 结肠靶向释放 溃疡性结肠炎 EUDRAGIT 

分 类 号：R943[医药卫生—药剂学]