新型载胰岛素口服给药系统的制备及其降血糖作用  

Preparation of novel oral Insulin-loaded drug delivery system and its hypoglycemic effect

作　　者：石海涛[1] 张志荣[2] 龚涛[2] 

机构地区：[1]丽珠集团丽珠医药研究所,广东珠海519020 [2]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2008年第1期22-25,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的用多孔羟基磷灰石微球(PHAMS)构建胰岛素口服给药系统,并考察给药系统的体外释药行为和糖尿病大鼠的降血糖效果。方法胰岛素吸附于PHAMS之后,采用乳化-溶剂挥发法进行Eudragit(-L100包衣,所得微球于0.1 mol.L-1HC l和磷酸盐缓冲液(PBS,pH6.8)中进行体外释药实验和糖尿病大鼠的降血糖试验。结果所得微球的载药量为0.49%,包封率为84.48%±1.07%。体外释药实验显示,在酸性介质中微球不释药,而在磷酸盐缓冲液中,超过96%的胰岛素在4 h内释放。动物试验表明,微球能够显著降低糖尿病大鼠的血糖水平达3 h(P<0.05),血糖水平最大下降34.7%,和皮下注射胰岛素相比,其相对生物利用度为4.3%。结论可以使用PHAMS构建胰岛素口服给药系统。OBJECTIVE To fabricate an oral drug release delivery system with porous hydroxyapatite microspheres （PHAMS） for insulin, to evaluate the drug release profiles in vitro and oral efficacy in diabetic rats. METHODS Insulin was adsorbed on PHAMS and then microencapsulated into Eudragit - L100 by a modified emulsion - solvent evaporation technique. The drug release profiles in vitro were evaluated in 0. 1 mol· L^-1 HCl and phosphate buffer solution （ PBS, 0. 05 mol· L^-1, pH6. 8 ）, its hypoglycemic effect at dose of 20 IU · kg^-1 in 16 streptozocin - induced diabetic rats. RESULTS The drug loading of the obtained microcapsules was 0. 493% ±0. 001% and encapsulation efficiency 84.48% ± 1.07%. In drug release experiment, no release was observed in acidic medium. However, more than 96% encapsulated insulin was released within 4 h in phosphate buffer solution. In in vivo studies, these microcapsules could reduce the blood glucose level （BGL） of diabetic rats for more than 3 h with maximal value of 34. 7% at 2 h after administration, showing statistically significant effect （ P 〈 0. 05 ）. Compared to subcutaneous injection of insulin, the obtained microcapsules demonstrated a bioavailability of 4. 3%. CONCLUSION These results suggest that we can be able to fabricate an oral proteinic drug delivery system with PHAMS.

关 键 词：羟基磷灰石 胰岛素 微球 包衣 优特奇 

分 类 号：R94[医药卫生—药剂学] R96[医药卫生—药学]