NTI-ADDAE Kvame V. (US),НТИ-АДДАЕ Кваме В. (US),UOLDO Majkl (US),УОЛДО Майкл (US),O'NIL Sajmon Adam (US),О'НИЛ Саймон Адам (US),VAN ALSTEN Dzhon Gregg (US),ВАН АЛЬСТЕН Джон Грегг (US),MATSIKENAS Dajni
申请号：
RU2016122611
公开号：
RU0002700415C1
申请日:
2014.11.12
申请国别(地区):
RU
年份:
2019
代理人:
摘要：
FIELD: chemistry.SUBSTANCE: invention relates to a novel crystalline salt of HCl compound (1)⋅1/2H2O (form A). Compound (1) is represented by the following structural formula:.Crystalline salt of HCl compound (1)⋅1/2H2O is characterized by peaks corresponding to 2-theta measured in degrees equal to 10.5±0.2, 5.2±0.2, 7.4±0.2 and 18.9±0.2 on a powder X-ray diffraction pattern, and additionally with peaks corresponding to 2-theta values measured in degrees equal to 25.2±0.2, 16.5±0.2, 18.1±0.2 and 23.0±0.2 on powder X-ray diffraction pattern. Crystalline form is also characterized by peaks corresponding to 29.2±0.3 ppm, 107.0±0.3 ppm, 114.0±0.3 ppm and 150.7±0.3 ppm in spectrum SSNMR on C13, and further characterized by peaks corresponding to 22.1±0.3 ppm, 24.6±0.3 ppm, 47.4±0.3 ppm and 54.8±0.3 ppm in spectrum SSNMR on C13. Crystalline form A is obtained by mixing HCl with compound (1) in a solvent system which includes water and one or more organic solvents, where the solvent system has water activity equal to 0.05–0.85, and where one or more organic solvents are selected from a group consisting of chlorobenzene, cyclohexane, 1,2-dichloroethane, dichloromethane, 1,2-dimethoxyethane, 1,4-dioxane, hexane, 2-methoxyethanol, methylbutyl ketone, methylcyclohexane, nitromethane, tetralin, toluene, 1,1,2-trichloroethane, xylene, acetone, anisole, 1-butanol, 2-butanol, butyl acetate, tert-butyl methyl ether, cumene, ethanol, ethyl acetate, ethyl ether, ethyl formate, heptane, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methyl ethyl ketone, 2-methyl-1-propanol, pentane, 1-pentanol, 1-propanol, 2-propanol, propyl acetate, tetrahydrofuran and methyl tetrahydrofuran. Invention also relates to a method for reducing the amount of influenza virus in a biological sample in vitro or in an individual, as well as a method of treating influenza using crystalline form A salt or a pharmaceutical composition. Amount of administered dose in treatment ranges fro
