The invention relates to the area of
medicinal chemistry,
pharmacology and
medicine and includes description of pharmaceutical compositions and combined medicaments on the base of
secretion stimulators and protectors of
incretin hormones for treatment of metabolic diseases (among them, diabetes,
obesity,
metabolic syndrome and the like). The invention consists in that that pharmaceutical composition or combined medicament comprises a derivative of tetrahydrobenzo[f][1,4]
oxazepine—either
nonsteroidal agonist of bile aids
receptor TGR5, or one of endogenous bile acids which stimulate
incretin hormones
secretion, and also one of the known inhibitors of DPP-IV proteinase. In this case administration of TGR5 agonists is carried out peroral, and administration of endogenous bile acids is exercised rectal in the form of
suppository or gel. As proteinase DPP-IV inhibitors could be used
Vildagliptin,
Saxagliptin,
Sitagliptin, Teneligliptin,
Linagliptin, Dutogliptin,
Alogliptin, Gemigliptin, Carmegliptin and the like. Besides, the invention includes description of novel tetrahydrobenzo[f][1,4]
oxazepine derivatives—
nonsteroidal agonist of bile aids receptors TGR5, and also methods for their preparation. The invention provides enhancement of therapy effectiveness owing to synergetic action of the components, thus making possible simultaneous treatment of diabetes, and
obesity, other metabolic diseases and their cardiovascular and renal complications.