Fukuda Y, Tsuji T, Fujita T, Yamamoto A, Muranishi S
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Biol Pharm Bull. 1995 Jun;18(6):891-4. doi: 10.1248/bpb.18.891.
The objective of this study was to determine the stability of insulin in rat lung homogenate and to confirm the effectiveness of various protease inhibitors for insulin delivery from the lung. The stability of insulin in rat lung homogenate was compared with that in the small intestine. Insulin was rapidly degraded in lung homogenate similarly to degradation in the small intestinal homogenate. The effects of various protease inhibitors on the degradation of insulin were studied in the lung. Protease inhibitors such as Na-glycocholate (Na-GC; 10 mM), aprotinin (10 mg/ml), soybean trypsin inhibitor (STI; 10 mg/ml) and bacitracin (20 mM) effectively reduced insulin degradation in lung homogenate. The rank order of effectiveness for decreasing the insulin hydrolysis in lung homogenate was bacitracin > aprotinin > STI > Na-GC. In addition, a slight correlation was observed between the in situ pulmonary absorption of insulin and its stability in vitro in the lung homogenate in the presence of various protease inhibitors. These findings suggest that the coadministration of protease inhibitors would be useful for improving the stability of insulin in the lung.
本研究的目的是确定胰岛素在大鼠肺匀浆中的稳定性，并证实各种蛋白酶抑制剂对胰岛素经肺递送的有效性。将胰岛素在大鼠肺匀浆中的稳定性与在小肠中的稳定性进行了比较。胰岛素在肺匀浆中迅速降解，类似于在小肠匀浆中的降解。研究了各种蛋白酶抑制剂对肺中胰岛素降解的影响。蛋白酶抑制剂如甘氨胆酸钠（Na-GC；10 mM）、抑肽酶（10 mg/ml）、大豆胰蛋白酶抑制剂（STI；10 mg/ml）和杆菌肽（20 mM）可有效减少肺匀浆中胰岛素的降解。降低肺匀浆中胰岛素水解的有效性排序为杆菌肽>抑肽酶>STI>Na-GC。此外，在各种蛋白酶抑制剂存在的情况下，观察到胰岛素的原位肺吸收与其在肺匀浆中的体外稳定性之间存在轻微相关性。这些发现表明，联合使用蛋白酶抑制剂将有助于提高胰岛素在肺中的稳定性。
