Takeyama M, Ishida T, Kokubu N, Komada F, Iwakawa S, Okumura K, Hori R
Department of Pharmacy, Kagawa Medical School, Japan.
Pharm Res. 1991 Jan;8(1):60-4. doi: 10.1023/a:1015878222769.
The present study was undertaken to develop an ointment preparation containing a protease inhibitor for stabilizing subcutaneously injected insulin. The ointment containing the protease inhibitor, gabexate mesilate or nafamostat mesilate, was applied to the skin around the insulin injection site. Three results were obtained. First, gabexate and nafamostat inhibited insulin degradation in subcutaneous tissue homogenates in vitro. Second, after application of gabexate or nafamostat ointment, an appreciable amount of gabexate or nafamostat appeared in the subcutaneous tissue of rats or hairless mice and their concentrations were comparable to those seen in the in vitro experiment. Third, insulin degradation at the subcutaneous injection site in the rat was depressed after pretreatment with gabexate or nafamostat ointment. Pretreatment with gabexate or nafamostat ointment increased the plasma immunoreactive insulin (IRI) levels and the hypoglycermic effect of insulin in healthy volunteers. These results indicate that gabexate or nafamostat ointments stabilize subcutaneously injected insulin.
本研究旨在开发一种含有蛋白酶抑制剂的软膏制剂，用于稳定皮下注射胰岛素。将含有蛋白酶抑制剂甲磺酸加贝酯或甲磺酸萘莫司他的软膏应用于胰岛素注射部位周围的皮肤。获得了三个结果。第一，甲磺酸加贝酯和甲磺酸萘莫司他在体外抑制皮下组织匀浆中的胰岛素降解。第二，应用甲磺酸加贝酯或甲磺酸萘莫司他软膏后，大鼠或无毛小鼠的皮下组织中出现了相当数量的甲磺酸加贝酯或甲磺酸萘莫司他，其浓度与体外实验中的浓度相当。第三，用甲磺酸加贝酯或甲磺酸萘莫司他软膏预处理后，大鼠皮下注射部位的胰岛素降解受到抑制。用甲磺酸加贝酯或甲磺酸萘莫司他软膏预处理可提高健康志愿者的血浆免疫反应性胰岛素（IRI）水平和胰岛素的降血糖作用。这些结果表明，甲磺酸加贝酯或甲磺酸萘莫司他软膏可稳定皮下注射的胰岛素。
