INCRETIN HORMONE SECRETION STIMULATORS, METHOD FOR PRODUCING AND USING SAME

摘要

The invention relates to the field of medicinal chemistry, pharmacology and medicine and contains a description of pharmaceutical compositions and combination drugs based on secretion stimulators and protectors of incretin hormones for the treatment of metabolic diseases (including diabetes, obesity, metabolic syndrome, etc.). The essence of the invention is that the pharmaceutical composition or combination drug contains a tetrahydrobenzo[f][1,4]oxazepine derivative which is a non-steroidal agonist of TGR5 bile acid receptors, or one of the endogenous bile acids, which stimulate the secretion of incretin hormones, as well as one of the known DPP-IV protease inhibitors. The TGR5 agonists are administered orally; the endogenous bile acids are administered rectally in the form of a suppository or gel. The following may be used as DPP-IV protease inhibitors: Vildagliptin, Saxagliptin, Sitagliptin, Teneligliptin, Linagliptin, Dutogliptin, Alogliptin, Gemigliptin, Carmegliptin, etc. In addition, the invention contains a description of novel derivatives of tetrahydrobenzo[f][1,4]oxazepine which are non-steroidal agonists of TGR5 bile acid receptors, as well as methods for the production thereof. The invention provides more effective therapy as a result of the synergistic action of the components, wherein it is possible to treat diabetes, obesity and other metabolic diseases and the cardiovascular and renal complications thereof simultaneously.