DIBENZO-AZEPINE COMPOUNDS AND USE THEREOF FOR TREATING EAR DISEASES AND DISORDERS Russian patent published in 2019 - IPC C07D223/18 A61K31/55 A61K47/02 A61K47/10 A61K47/32 A61K47/34 A61K47/36 A61K47/38 A61P27/16 

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I and II in crystalline form, characterized by an X-ray powder diffraction pattern with peaks at 8.2, 13.8, 14.0, 18.4 and 20.9±0.15 degrees two-theta (compound I) and X-ray powder diffraction pattern with peaks at 8.4, 15.2, 16.0, 20.6 and 22.6±0.15 degrees two-theta (compound II). Invention also relates to an aqueous pharmaceutical composition for treating auditory disorders for intratympanic introduction comprising (1) an active agent selected from a crystalline compound of formula I or II, and (2) a pharmaceutically acceptable aqueous solution containing (A) from 15 % to 25 % wt/wt. poloxamer 407; or (B) (I) from 15 % to 25 % wt/wt. poloxamer 407 and (II) from 0.5 % to 4 % wt/wt. hydroxypropyl methyl cellulose having nominal viscosity of 40–60 cP, or grade of 80–120 cP; or (C) (I) 10–20 % wt/wt. poloxamer 407 and (II) 0.1–0.3 % wt/wt. Carbopol^® 974P; or (D) (I) from 0.5 % to 8 % wt/wt. hyaluronic acid; or (E) (I) from 0.5 % to 4 % wt/wt. hyaluronic acid and (II) from 5 % to 20 % vol. polyethylene glycol 400; wherein said active agent is present in amount of 0.01 % to 20 % wt/wt. of said aqueous solution.

EFFECT: crystalline compounds of formula I and II are intended for preparing a drug for treating auditory disorders.

30 cl, 4 tbl, 6 dwg, 13 ex