L.I. Valuev, G.A. Sytov, L.V. Vanchugova, I.L. Valuev

It became evident that some peptides and proteins may create new drugs to cure several diseases. Nevertheless, the usage of proteins as drugs is limited by the availability of the route and method of their delivery. The oral administra-tion seems to be the most comfortable but it cannot be generally applied to proteins. Indeed, oral delivery of proteins must overcome next barriers build by the Nature in the living organism: their degradation in the stomach by the strong acidic environment and by the proteolytic enzymes; metabolism in the small intestine by the pancreatic proteolytic enzymes and the poor intestinal absorption of peptides. Here we report the novel approach to overcome barriers to insulin and other peptides absorption after oral administration of the solutions with very low concentration of these substances. The idea of the work presented here is based on the following. It is known that absorption of water by the stomach is negligible; the principle site for water absorption following a meal is the upper small intestine, when one liter of water containing D2O as a tracer is ingested, 50 % of the ingested deuterium appears in the blood in about 3 minutes. These facts allowed us to propose the existence of possibility for the rapid transport of dilute solutions of some substances, including proteins, through the stomach to the small intestine. Besides, from the kinetics of enzymatic reactions it can be expected the decrease of the rate of enzymatic hydrolysis of protein in the small intestine as a result of the decrease of substrate concentration. It is shown that after oral administration of diluted insulin solutions to the healthy animals and to the animals with experimental diabetes insulin passes very fast through the stomach, does not undergo the proteolytic degradation and its absorption is significant to produce the hypoglycaemic effect. The practically same results were obtained after oral administration of diluted insulin solutions to volunteers. The maximal decreasing of blood glucose level was about 30 %. The oral administration of lower (glucagon) and higher (growth hormone) molecular weight peptides also leads to the penetration of these compounds into bloodstream.