POLYMORPH OF YONKENAFIL HYDROCHLORIDE, METHOD FOR ITS PREPARATION AND COMPOSITION ON ITS BASIS AND ITS APPLICATION Russian patent published in 2018 - IPC C07D487/04 A61K31/519 A61P15/10 

FIELD: medicine; pharmaceuticals.

SUBSTANCE: invention relates to a new yonkenafil type A polymorph (monohydrochloride 2-[2-ethoxy-5-(4-ethylpiperazine-1-sulfonyl)phenyl]-5-methyl-7-n-propyl-3,7-dihydropyrrole[2,3-d]pyrimidin-4-one), possessing the properties of a phosphodiesterase type 5 inhibitor (PDE-5), a method for its preparation, a pharmaceutical composition based on it and its application. Polymorph is used to produce a drug to treat or prevent erectile dysfunction in a male animal and diseases associated with phosphodiesterase type 5. Type polymorph has diffraction peaks on a powder diffractogram with three or more values 2θ, selected from: 8.4 ± 0.2°, 11.3 ± 0.2°, 13.9 ± 0.2°, 14.2 ± 0.2°, 14.7 ± 0.2°, 16.8 ± 0.2°, 17.1 ± 0.2°, 19.7 ± 0.2°, 21.0 ± 0.2°, 21.7 ± 0.2°, 22.4 ± 0.2°, 23.3 ± 0.2°, 23.8 ± 0.2°, 26.8 ± 0.2°, 27.5 ± 0.2°, 28.0 ± 0.2°. Polymorph cell parameters are essentially the following: cell size: a (Å) is 19.1 ± 0.1; b (Å) is 12.7 ± 0.1; c (Å) is 11.3 ± 0.1; volume is 2741 ± 30 ų; space group is a P2₁/s; density is 1.31 ± 0.01 g/cm³. Thermogram of the differential scanning calorimetry of the polymorph contains endothermic peaks at 34–133 °C and 231–250 °C, respectively, preferably endothermic peaks at 86.4 °C and 237.9 °C respectively. Method of obtaining polymorph type a of yonkenafil hydrochloride includes: suspending yonkenafil hydrochloride in water or water with alcohol, heating with dissolving yonkenafil hydrochloride, slow cooling and crystallization, filtering with collecting solids and drying to obtain polymorph type A of yonkenafil hydrochloride or achieving equilibrium when dissolving yonkenafil hydrochloride in water or water with alcohol, filtering and drying to obtain yonkenafil hydrochloride type A polymorph. Alcohol is preferably selected from ethanol or methanol or a mixture thereof. Typically, the volume ratio of alcohol to water is from 95:5 to 0:100. Heating temperature ranges from room temperature to 90 °C. Slow cooling is cooling to a temperature ranging from -10 °C to -5 °C. Resulting crystalline form is highly stable compared to another polymorph B.

EFFECT: pharmaceutical composition may be in the form of a solid composition for oral use, such as a tablet, pill, capsule and powder, or in the form of a liquid composition for oral use, such as suspension, solution, emulsion and syrup.

15 cl, 3 dwg, 4 ex