ORAL LONG-ACTING PHARMACEUTICAL FORM OF INSULIN ON THE BASIS OF SELF-ORGANIZING KVASI-LIVING SYSTEM OF COMBINATORIAL PEPTIDES

The paper discusses the results of studies on physical and chemical properties of kvasi-living self-organizing insulin-based system, and on the effectiveness of its oral administration. The purpose of the studies was to modify positively charged amino acid residues into negatively charged residues of dicarboxylic acids. The process of bioorganic combinatorial synthesis produced more than 100 thousand fragments capable of self-organization in the insulin receptor. Self-organization is due to the fact that peptides were previously a part of the whole – namely, insulin molecule. These peptides had small size, and could be easily absorbed by intestines. They also had a long duration of circulation in blood and reacted with insulin receptor in a fashion similar to injected insulin. It is shown that a single oral application of such system leads to statistically significant and sustained reduction in blood glucose levels within 24 hours of application. The effect is observed in both cases: while taking the drug on an empty stomach, and with glucose and food load up to 7.11 mmol / L. A single dose of the drug led to a plateau of stable glucose levels and prevented hypoglycemia and glucose level jumps when applied to rats (control group). The kvasi-living system was obtained by partial proteolysis of recombinant insulin with pepsin, followed by partial modification of peptides with succinic anhydride