结肠定位盐酸小檗碱羧甲基魔芋胶小丸的体内外释药研究

Studies on in Vitro and in Vivo Release of Berberine Hydrochloride from Carboxymethyl Konjac Glucomannan Pellets of Colonic Targeting Delivery

目的研究盐酸小檗碱羧甲基魔芋胶小丸体内外释药情况,评价其结肠定位释药特性。方法采用离子胶凝法制备羧甲基魔芋胶小丸,测定小丸在含不同浓度β-甘露聚糖酶的介质中药物释放和丸粒溶蚀情况,并对药物释放、丸粒溶蚀和酶浓度间的相关性进行研究;以盐酸小檗碱羧甲基纤维素钠混悬液为对照,采用HPLC测定大鼠灌胃给药后经时血药浓度和胃、小肠及结肠组织分布量,计算药物的相对靶向释药指数。结果小丸在模拟胃和小肠环境介质中,5h累积释放在20%以下,在模拟结肠环境的含酶介质中,14h药物释放达90%以上,随酶浓度增加,药物释放及丸粒溶蚀程度增加,药物释放量与丸粒溶蚀量呈近似1:1线性相关;与对照组相比,小丸组在大鼠胃、小肠、结肠组织的药物相对靶向释药指数值分别为0.3924,0.4786,4.193。结论盐酸小檗碱羧甲基魔芋胶小丸具有结肠定位释药特性。

OBJECTIVE To investigate in vitro and in vivo release of berberine hydroehloride（BH） from earboxymethyl konjac glucomannan（CMKGM） pellets for evaluating colon-specific drug delivery characteristics of the pellets. METHODS CMKGM pellets were prepared by ionotropic gelation technique, l）rug release and erosion properties of the pellets were measured in dissolution media with different β-mannase concentration to study the correlations between release of BH, erosion properties and β-mannase coneentration. Compared with BH-containing carboxymethyl cellulose suspension, the concentration of BH in plasma and gastric, entric,colonic tissue after intragastric administration to rats were measured by HPLC, and the relative targeting drug delivery index （DD1） was obtained. RESULTS The accumulated release of drug was less than 20% within 5 h in the artificial media of stomach and small intestine, while the release was more than 90% in the artificial medium of colon in 14 h. With the increased of β-mannase concentration, the release of BH and the erosion of the pellets was increased. The amount relationships of the release of BH and the erosion of the pellets were approximately 1： 1. The DDIs of the pellets were 0. 392 4,0. 478 6,4. 193 in gastric, entric, colonic tissue of the rat,compared with BH suspension, respectively. CONCLUSION BH-containing CMKGM pellets may be a useful colon-specific drug delivery system.