结肠定位盐酸小檗碱羧甲基魔芋胶小丸的研制

Study on preparation of berberine hydrochloride-loaded carboxymethyl konjac glucomannan colon-specific pellets

目的:研制结肠定位盐酸小檗碱羧甲基魔芋胶小丸。方法:以盐酸小檗碱为模型药物,采用滴制离子交联法制备小丸,以小丸包封率及在模拟胃、肠道上段介质中药物释放量为指标,通过单因素试验优化小丸制备工艺,并测定其体外释放度。结果:盐酸小檗碱羧甲基魔芋胶小丸的优化制备工艺为凝胶液pH为3,壳聚糖浓度为2.5g/L,氯化铁浓度为5 g/L,羧甲基魔芋胶浓度为20 g/L,药物/羧甲基魔芋胶配比为2∶1(w/w),热处理时间为10 h;小丸体外约物释放时,在模拟胃、肠道上段介质中,5 h药物累积释放在20%左右,在模拟结肠(含0.05 g/Lβ-甘露聚糖酶)介质中,12 h药物累积释放接近90%。结论:盐酸小檗碱羧甲基魔芋胶小丸具有潜在的结肠定位释药特性。

Objective： To prepare berberine hydrochloide（BH）-loaded carboxymethyl konjac glucomannan（CMKGM） pellets for colon-specific drug delivery. Methods： BH-loaded CMKGM pellets were prepared by adding CMKGM-BH suspension dropwise into FeCl; and chitosan coexisting gelling solution, then pellets were cured for some times. The entrapment efficiency and drug release in stimulated gastric and enteric media for 5h were taken as criterionsto optimize the preparation technology by single factor method. The release properties of BH from pellets were investigated. Results： The optimal conditions, the curing time of pellets, the pH value of gelling solution, the concentration of chitosail, FeCl3 and CMKGM aqueous solution, BH ratio to CMKGM were 10 h. pH3, 2. 5 g/L. 5 g/L, 20 , 2 ： 1 （w/w）, respectively. The cumulative release rate of pellets in the simulated gastric and enteric media was about 20 % for 5 h. and in the simulated colonic medium（ with 0.05 g/Lmannase） was about 90 % for 12 h. Conclusion： BH-loaded CMKGM pellets have the potential to release the drug targeting in the colon.