肠溶广藿香油滴丸制备及其对UC大鼠的药效评价

Preparation of enteric-coated patchouli oil dropping pills and its efficacy evaluation on UC rats

关键词:  广藿香油  肠溶滴丸  制备  溃疡性结肠炎  药效

Key words:  patchouli oil  enteric coated dropping pills  preparation  ulcerative colitis  pharmacodynamics

摘要:

目的 制备肠溶广藿香油滴丸，评价其对大鼠溃疡性结肠炎（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丸芯制备参数，再以体外溶出度考察确定Endragit包衣处方，最后评价制剂对2，4，6-三硝基苯磺酸（TNBS）诱导的大鼠UC模型的治疗作用。通过记录给药组的疾病活动指数（DAI）、体重变化等指标，观察并分析结肠组织HE染色切片；通过ELISA法和qPCR法测定炎症细胞因子及屏障蛋白的表达水平，系统评价肠溶广藿香油滴丸对实验性UC的治疗效果。结果 广藿香油滴丸的最优处方为PO : PEG6000 : PEG8000 比例1 : 1 : 1；最优工艺为滴速33滴/min、管口温度9℃、滴距6 cm；包衣最优处方为Endragit L100 : Endragit S100比例3 : 7。与广藿香油相比，肠溶广藿香油滴丸组明显改善了大鼠体重减轻、便血和结肠缩短等病理症状，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，结肠组织中粘蛋白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 肠溶广藿香油滴丸提高了药物的抗炎效果及结肠靶向释放能力，为广藿香油治疗UC新药开发提供了制备简单、药效明显的现代化剂型。

Abstract:

OBJECTIVE To prepare enteric-coated patchouli oil dripping pills and evaluate its therapeutic effect on ulcerative colitis (UC) in rats. Methods The single factor combined with response surface optimization method was used to screen the matrix types and optimize the preparation parameters of the pill core, and then the Endragit coating prescription was determined by in vitro dissolution. Finally, the therapeutic effect of the preparation on the rat UC model induced by 2,4,6-trinitrobenzene sulfonic acid ( TNBS ) was evaluated. By recording the disease activity index ( DAI ), weight change,and other indicators of the administration group, the HE staining sections of colon tissue were observed and analyzed. The expression levels of inflammatory cytokines and barrier proteins were determined by ELISA and qPCR, and the therapeutic effect of enteric-coated patchouli oil dropping pills on experimental UC was systematically evaluated. RESULTS The optimal prescription of patchouli oil dropping pills was PO : PEG6000 : PEG8000 ratio of 1 : 1 : 1 ; the optimal process is as follows : dropping speed 33 drops / min, nozzle temperature 9 °C, dropping distance 6 cm ; the optimal coating prescription was Endragit L100 : Endragit S100 ratio of 3 : 7. Compared with Pogostemon cablin oil, the Pogostemon cablin oil enteric-coated dropping pill group significantly improved 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-α was significantly down-regulated. CONCLUSION The enteric-coated patchouli oil dropping pills improve the anti-inflammatory effect and colon-targeted release ability of the drug, and provide a modern dosage form with simple preparation and obvious efficacy for the development of new drugs for the treatment of UC with patchouli oil.