左金果胶胶囊的处方优化及其对胃溃疡模型大鼠的保护作用

杨贵前 刘文 陶玲 沈祥春 宋朔尧 张环 李和蓉 王守莉 石惠云

中圖分类号 R944.5;R285 文献标志码 A 文章编号 1001-0408（2021）19-2327-09

DOI 10.6039/j.issn.1001-0408.2021.19.04

摘 要 目的：优化左金果胶胶囊的处方，制备对胃溃疡具有保护作用的现代左金果胶胶囊剂。方法：以果胶、可溶性淀粉、糊精含量为考察因素，以胶囊剂中颗粒的成型性、吸湿性、流动性为考察指标，采用正交实验优化左金果胶胶囊的处方。以左金提取物浸膏粉末为原料，采用湿法制粒填充法制备左金果胶胶囊。采用高效液相色谱法测定左金果胶胶囊中盐酸巴马汀、盐酸小檗碱、吴茱萸碱、吴茱萸次碱的含量，并采用转篮法考察该胶囊剂在0.1 mol/L盐酸溶液中的体外释药行为。通过灌胃75%乙醇复制胃溃疡大鼠模型，以胃溃疡指数、胃溃疡抑制率和胃组织病理切片结果为指标，初步考察左金果胶胶囊（剂量分别为54、108、216 mg/kg）的胃溃疡保护作用。结果：左金果胶胶囊的最优处方为果胶含量45%、可溶性淀粉含量12%、糊精含量27%、木糖醇含量1%。体外释放结果表明，1 h时左金果胶胶囊中盐酸巴马汀和盐酸小檗碱分别释放了53.76%、54.82%，二者均在8 h左右释放完全，且均符合零级释放行为。不同剂量左金果胶胶囊均能不同程度地改善胃溃疡模型大鼠胃组织的溃疡损伤，显著降低其胃溃疡指数（P<0.01），显著升高其胃溃疡抑制率和碘酸雪夫氏染色阳性表达面积百分比（P<0.01）。结论：成功制得对胃溃疡具有保护作用并具有一定缓释效应的左金果胶胶囊。

关键词 左金果胶胶囊;胃溃疡;正交实验;缓释效应;大鼠

Formulation Optimization of Zuojin Pectin Capsule and Its Protective Effect on Gastric Ulcer Model Rats

YANG Guiqian1，LIU Wen1，2，TAO Ling1，SHEN Xiangchun1，SONG Shuoyao1，ZHANG Huan1，LI Herong1，WANG Shouli1，SHI Huiyun1（1. School of Pharmacy， Guizhou Medical University/Engineering Center for the Highly Efficient Utilization of Natural Medicine Resources in Guizhou Province/Key Lab for Pharmacology and Pharmacogenesis Evaluation of Natural Medicine in Guizhou Universities/Guizhou Medical University-Guiyang Joint Key Laboratory/Key Laboratory for Optimal Utilization of Natural Medicine Resources，Guiyang 550025，China; 2. The Affiliated Hospital of Guizhou Medical University， Guiyang 550025， China）

ABSTRACT   OBJECTIVE： To optimize the formulation of Zuojin pectin capsules， and to prepare modern Zuojin pectin capsules with protective effects against gastric ulcers. METHODS： The formulation of Zuojin pectin capsules was optimized with orthogonal test with the contents of pectin， soluble starch and dextrin as factors， using formability， moisture absorption and flow ability as indicators. Zuojin pectin capsule was prepared by wet granulation filling method with Zuojin extract powder as raw material. The contents of palmatine hydrochloride， berberine hydrochloride， evodiamine and rutaecarpin were evaluated by HPLC. Basket method was used to investigate the release behavior of the capsule in 0.1 mol/L HCl solution. The gastric ulcer model of rats was established by intragastric administration of 75% ethanol. Gastric ulcer index， the inhibition rate of gastric ulcer and the pathological sections were used as indexes to investigate the protective effect of Zuojin pectin capsules （the doses were 54， 108， 216 mg/kg） on gastric ulcer. RESULTS： The optimal formulation of Zuojin pectin capsules included 45% pectin， 12% soluble starch， 27% dextrin and 1% xylitol. Results of in vitro drug release showed that palmatine hydrochloride and berberine hydrochloride in Zuojin pectin capsules released 53.76% and 54.82% respectively within 1 h， completely released at about 8 h， and conformed to the zero-order release behavior. Different doses of Zuojin pectin capsule could improve the ulcer injury of gastric tissue in gastric ulcer model rats to different extent， and significantly reduced the gastric ulcer index （P<0.01）， significantly increased the inhibition rate of gastric ulcer and the percentage of positive expression area of Schiffs iodate staining （P<0.01）. CONCLUSIONS： Zuojin pectin capsule with protective effect on gastric ulcer and certain sustained- release effect is successfully prepared.