Phenylalanine Derivatives Enhancing Intestinal Absorption of Insulin in Mice

The adjuvant effect of N-acyl-L-and D-phenylalanine derivatives on intestinal absorption of insulin was investigated in normal mice. The correlation between the chemical structural properties of the N-acyl moiety and the absorption-promoting activity was estimated from the glucose concentrations and the insulin levels in the blood of mice after oral combined administration of insulin and adjuvant. The chemical structural properties of N-acyl-phenylalanine derivatives necessary for adjuvant effect on intestinal absorption of insulin were as follows.1. An aromatic ring is present, separated by two atoms from the acyl carbonyl group.2. Either of X or Y is oxygen or X-Y is a double bond in Fig.2.3. The N-acyl moiety has small hydrophobic substituents, such as F, Cl, or Me at Rα, Rβ, Rη and has an appropriate hydrophilic-hydrophobic balance of the overall molecule.The use of these agents to enhance insulin absorption offers the possibility of a new approach to oral insulin therapy.