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目的 观察改变了材料分子量、微囊粒径后的聚丙交酯胰岛素微囊 (PL A- MCI)体外释药及大鼠口服后血糖的变化。方法 体外释药在磷酸盐缓冲液 (PBS)中进行 ,胰岛素测定用福林 -酚法。体内实验由糖尿病大鼠口服 PL A- MCI后每小时血糖测定反映 ,并与口服纯胰岛素的二组对照及同期饥饿对照组血糖进行比较。结果 PL A- MCI在 PBS中 3～ 7小时内释放了 5 1.0 %～ 73.4%的胰岛素 ,11小时后释放达稳态。口服 PL A- MCI后大鼠血糖下降达 80 .9± 10 .8%(n=10 ) ,显著高于口服等量纯胰岛素的正常大鼠 (31.0± 15 .1% ,n=6 )和糖尿病大鼠 (47.0± 2 7.9% ,n=5 )以及未服药同期饥饿对照糖尿病大鼠 (40 .0± 16 .7% ,n=7) (P均 <0 .0 0 1)。PL A- MCI与水预混 1小时后口服 ,体内降血糖峰时为 1～ 3小时 ,持续作用 10～ 12小时。PL A- MCI在 PBS液中温育 3周 ,电镜下仍见基本完整形态。结论 减少 PL A分子量 ,增加微球粒径加快了胰岛素从 PL A- MCI中的释放 ,提高了其口服后降血糖效应 ,并保持其缓慢降解特性 ,具有良好的安全性。
Objective To observe the in vitro release of polylactide insulin microcapsules (PL-MCI) after changing the molecular weight and the size of microcapsules, and the changes of blood glucose after oral administration in rats. Methods In vitro drug release was performed in phosphate buffered saline (PBS). Insulin was measured using the Fulin-Phenol method. The in vivo experiments were performed on diabetic rats with oral glucose tolerance test (PL-MCI) after oral administration of PL-MCI. The results were compared with those of the control group and the starved control group. Results PL A-MCI released 5 1.0% to 73.4% of insulin within 3 to 7 hours in PBS and reached steady state after 11 hours. After oral administration of PL-MCI, the blood glucose of rats decreased by 80.9 ± 10.8% (n = 10), significantly higher than that of normal rats (31.0 ± 15.1%, n = 6) Diabetic rats (47.0 ± 2 7.9%, n = 5) and diabetic rats without control (40 .0 ± 16 .7%, n = 7) all had the same dose (P <0.01). PL A-MCI and water pre-mixed after 1 hour oral administration, the body hypoglycemic peak for 1 to 3 hours, the sustained effect of 10 to 12 hours. PL A-MCI incubated in PBS solution for 3 weeks, the basic integrity is still seen under electron microscopy. Conclusion Reducing the molecular weight of PL A and increasing the particle size of PLA accelerated the release of insulin from PL-MCI, increased its hypoglycemic effect after oral administration, and maintained its slow degradation characteristics with good safety.