Kimura T, Sato K, Sugimoto K, Tao R, Murakami T, Kurosaki Y, Nakayama T
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Biol Pharm Bull. 1996 Jun;19(6):897-900. doi: 10.1248/bpb.19.897.
The oral administration of insulin in poly(vinyl alcohol)-gel spheres (PVA-GS), an oral dosage form with prolonged residence time in the ileum, was examined in streptozotocin-induced diabetic rats. Intragastric administration of PVA-GS containing insulin and a protease inhibitor, aprotinin or bacitracin, caused a significant and prolonged reduction of blood glucose levels, suggesting insulin absorption. The bioavailability of insulin estimated from the hypoglycemic effect was about 2% in the presence of either protease inhibitor. The release profiles of insulin and the protease inhibitors from the PVA-GS could be explained by Higuchi's plot, and the rates were similar to each other. The site dependency of insulin absorption in the intestinal tract was examined by an in situ loop method. Insulin absorption estimated by plasma insulin levels was larger in the ileum and the large intestine than in the jejunum. The prolonged residence time of PVA-GS in the absorption site, the lower intestine, and the synchronous release of insulin and the protease inhibitors from the PVA-GS are the two major explanations for the improved bioavailability of insulin administered as PVA-GS containing a protease inhibitor.
在链脲佐菌素诱导的糖尿病大鼠中，研究了胰岛素在聚乙烯醇凝胶球（PVA - GS）中的口服给药情况，PVA - GS是一种在回肠中具有延长停留时间的口服剂型。胃内给予含有胰岛素和蛋白酶抑制剂抑肽酶或杆菌肽的PVA - GS，可导致血糖水平显著且持续降低，提示胰岛素吸收。在存在任何一种蛋白酶抑制剂的情况下，根据降血糖作用估算的胰岛素生物利用度约为2%。胰岛素和蛋白酶抑制剂从PVA - GS中的释放曲线可用Higuchi图解释，且释放速率彼此相似。通过原位肠袢法研究了肠道中胰岛素吸收的部位依赖性。通过血浆胰岛素水平估算的胰岛素吸收在回肠和大肠中比在空肠中更大。PVA - GS在吸收部位（下肠道）的延长停留时间以及胰岛素和蛋白酶抑制剂从PVA - GS中的同步释放是含蛋白酶抑制剂的PVA - GS给药后胰岛素生物利用度提高的两个主要原因。
