Кристаллическая η-модификация 2-амино-2-(2-(4-октилфенил)этил)пропан-1,3-диол гидрохлорида, способ её получения и фармацевтическая композиция на её основе
Mikhajlov Oleg Rostislavovich,Михайлов Олег Ростиславович,Uvarov Nikolaj Aleksandrovich,Уваров Николай Александрович,Malin Aleksandr Aleksandrovich,Малин Александр Александрович
申请号：
RU2016127214
公开号：
RU0002627691C1
申请日:
2016.07.06
申请国别(地区):
RU
年份:
2017
代理人:
摘要：
FIELD: pharmacology.SUBSTANCE: invention relates to a new crystalline ηmodification of 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol hydrochloride (fingolimod hydrochloride), its preparation method and application. This crystalline ηmodification can be used to prepare a pharmaceutical composition as an immunosuppressant for treatment of relapsing-remitting multiple sclerosis. Crystalline ηmodification of 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol hydrochloride is characterized by the following set of interplanar distances (d, E) and their corresponding intensities (Irel., %) 25.199 - 100.00% 12.569 - 4.46% 8.362 - 8.20% 7.171 - 3.10% 6.705 - 1.11% 5.841 - 5.94% 4.985 - 2.63% 4.572 - 4.96% 4.341 - 9.98% 4.176 - 8.11% 4.073 - 4.77% 3.867 - 4.27% 3.776 - 2.14% 3.581 - 3.02% 3.393 - 3.34% 3.185 - 1.07% 3.069 - 2.65% 3.005 - 1.17% 2.991 - 1.13% 2.842 - 1.25% 2.802 - 1.56%, as well as by a set of endothermic effects on the DSC curve at temperatures (40.7±0.5)°C (107.6±0.5)°C (261.5±0.5)°C. A method for production of a crystalline ηmodification of 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol hydrochloride includes freezing of an aqueous solution of fingolimod hydrochloride with a concentration of 0.5-8.0 wt %, at 25-100°C, acidified with hydrochloric acid to pH=(5-2), at a cooling rate of at least 60 deg/min and freeze dried. It is desirable to freeze dry the frozen solution of fingolimod hydrochloride at the following temperatures: (-43…-75)°C on the condenser (-196…+50)°C on the product, and the residual pressure of (9-3)×10-2 Torr in the chamber, for 22-26 hours.EFFECT: method allows to obtain a pure stable crystalline modification, which is a powder of white or almost white colour, odorless, water soluble, readily soluble in low molecular weight alcohols, dimethylsulfoxide, practically insoluble in acetonitrile.4 cl, 6 dwg, 4 tbl, 4 exИзобретение относится к новой кристаллической η-модификации гидрохлорида 2-амино-2-(2-(4-октилфенил)этил)пропан-1,3-д
