Enzymatic and hyperglycemia stability of chemically modified insulins with hydrophobic acyl groups.

The acylated insulins were synthesized by the reaction of insulin protected by p-methoxybenzoxy carbonyl azide at Gly-A1 site with N-hydroxysuccinimide ester of caproic acid or benzoic acid (Cap-insulin and Bz-insulin). The noteworthy aspects are as follows: (a) the acylated insulins were more stable to the decomposition by various digestive enzymes as compared with native insulin in vitro. (b) Animal experiments using normal rats in vivo revealed that the Bz-insulin had an effective hypoglycemia activity almost similar to that of native insulin.