H3-LIGAND TETRAHYDRATE, ITS PRODUCTION METHOD, AND PHARMACEUTICAL COMPOSITIONS CONTAINING IT Russian patent published in 2022 - IPC C07D401/12 A61K31/4545 A61P25/16 A61P25/28 A61P43/00 

FIELD: pharmaceutical chemistry.

SUBSTANCE: group of inventions relates to the field of pharmaceutical chemistry and includes methods for the production of a tetrahydrate form of (3S)-4-{4-[3-(3-methylpiperidine-1-yl)propoxy]phenyl}pyridine 1-dihydrochloride oxide (compound (A)) and a pharmaceutical compositions based on it. The resulting tetrahydrate form is characterized by a water content of 15.3 ± 0.7% by weight and demonstrates following lines of the powder X-ray diffraction pattern: 2-theta ° (d in Angstroms) = 9.7 (9.1), 12.5 (7.1), 14.6 (6.1), 15.2 (5.8), 16.5 (5.4), 19.0 (4.7), 19.5 (4.6), 22.0 (4.1), 24.3 (3.7), 24.8 (3.6), 26.2 (3.4), 28.4 (3.1). One of production methods includes dissolution of the compound (A) in water, concentration until crystallization by evaporation of water in vacuum, filtration and drying of solid substance at a temperature from 20 to 40°C to the desired final water content from 14.6 to 16.0% by weight. Another method for the production of the tetrahydrate form of the compound (A) is dissolution of the compound (A) in water, addition of acetone and lowering of the temperature to a value in the range from 20 to 40°C before crystallization, filtration and drying of solid substance at a temperature from 20 to 40°C to the desired final water content from 14.6 to 16.0% by weight. A method for producing a pharmaceutical composition characterized by affinity to H3 receptor consists in obtaining a tetrahydrate form of the compound of the formula (A) by one of the specified methods and mixing the resulting tetrahydrate form with one or several pharmaceutically acceptable auxiliary substances.

EFFECT: production of a tetrahydrate form of the compound (A), which is stable under normal conditions, and a pharmaceutical composition based on it.

3 cl, 2 dwg, 6 ex