左金果膠膠囊的處方優化及其對胃潰瘍模型大鼠的保護作用

楊貴前 劉文 陶玲 沈祥春 宋朔堯 張環 李和蓉 王守莉 石惠云

中圖分類號 R944.5;R285 文獻標志碼 A 文章編號 1001-0408（2021）19-2327-09

DOI 10.6039/j.issn.1001-0408.2021.19.04

摘 要 目的：優化左金果膠膠囊的處方，制備對胃潰瘍具有保護作用的現代左金果膠膠囊劑。方法：以果膠、可溶性淀粉、糊精含量為考察因素，以膠囊劑中顆粒的成型性、吸濕性、流動性為考察指標，采用正交實驗優化左金果膠膠囊的處方。以左金提取物浸膏粉末為原料，采用濕法制粒填充法制備左金果膠膠囊。采用高效液相色譜法測定左金果膠膠囊中鹽酸巴馬汀、鹽酸小檗堿、吳茱萸堿、吳茱萸次堿的含量，并采用轉籃法考察該膠囊劑在0.1 mol/L鹽酸溶液中的體外釋藥行為。通過灌胃75%乙醇復制胃潰瘍大鼠模型，以胃潰瘍指數、胃潰瘍抑制率和胃組織病理切片結果為指標，初步考察左金果膠膠囊（劑量分別為54、108、216 mg/kg）的胃潰瘍保護作用。結果：左金果膠膠囊的最優處方為果膠含量45%、可溶性淀粉含量12%、糊精含量27%、木糖醇含量1%。體外釋放結果表明，1 h時左金果膠膠囊中鹽酸巴馬汀和鹽酸小檗堿分別釋放了53.76%、54.82%，二者均在8 h左右釋放完全，且均符合零級釋放行為。不同劑量左金果膠膠囊均能不同程度地改善胃潰瘍模型大鼠胃組織的潰瘍損傷，顯著降低其胃潰瘍指數（P<0.01），顯著升高其胃潰瘍抑制率和碘酸雪夫氏染色陽性表達面積百分比（P<0.01）。結論：成功制得對胃潰瘍具有保護作用并具有一定緩釋效應的左金果膠膠囊。

關鍵詞 左金果膠膠囊;胃潰瘍;正交實驗;緩釋效應;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.