INCRETIN HORMONE SECRETION STIMULATORS, METHOD FOR PRODUCING AND USING SAME

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. L'invention concerne le domaine de la chimie médicale, de pharmacologie et de médecine et comprend une description de compositions pharmaceutiques et de produits médicamenteux combinés sur la base des stimulateurs de sécrétion et protecteur des hormones d'incrétine pour traiter des troubles métaboliques (y compris le diabète, l'obésité, le syndrome métabolique, etc.). L'invention consiste en ce que la composition pharmaceutique ou le produit médicamenteux combiné comprend un dérivé de tétrahydrobenzo [f][1,4]oxazépine - agoniste non stéroïde des récepteurs d'acides foliques TGR5, ou l'un des acides foliques endogènes qui stimulent la sécrétion des hormones d'incrétine ainsi que l'un des inhibiteurs de protéinase connus à ce jour, DPP-IV. L'administration des agonistes de TGR5 se fait par voie pérorale, et l'introduction des acides foliques endogènes s'effectue par voie rectale, sous forme de suppositoire ou de gel. En tant qu'inhibiteur de la protéinase DPP-IV on peut utiliser Vildagliptine, Saxagliptine, Sitagliptine, Ten