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КРИСТАЛЛИЧЕСКАЯ БЕЗВОДНАЯ γ-МОДИФИКАЦИЯ 4-(3-ХЛОР-4-ФТОРАНИЛИНО)-7-МЕТОКСИ-6-(3-МОРФОЛИНОПРОПОКСИ)ХИНАЗОЛИН, СПОСОБ ЕЕ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ЕЕ ОСНОВЕ
专利权人:
Михайлов Олег Ростиславович (RU)
发明人:
Малин Александр Александрович (RU),Михайлов Олег Ростиславович (RU),Уваров Николай Александрович (RU)
申请号：
RU2014122245/04
公开号：
RU2014122245A
申请日:
2014.06.02
申请国别(地区):
RU
年份:
2015
代理人:
摘要：
1. Anhydrous crystalline γ-modification characterized by the following set-spacings (d, Å) and their respective intensities (I,%): 13,786 - 84,0% 12.569 - 53.6% 10.789 - 17.4% 10.659 - 13.2% 9,513 - 14.3% 8.284 - 12.4% 7.914 - 28.1% 7.171 - 29.6% 6,840 - 26.2% 6,314 - 44.3% 6,243 - 34.1% 5,803 - 62.0% 5.599 - 54.8% 5,435 - 39.6% 5,376 - 26.2% 5,024 - 32.1% 4,808 - 35.2% 4,595 - 100.0% 4,418 - 49.1% 4,070 - 28.5% 3,972 - 39.5% 3.914 - 26.6% 3,707 - 67.8% 3,668 - 88.4% 3,630 - 38.5% 3,484 - 58.7% 3,424 - 70.5% 3,378 - 92.0% 3,256 - 22.4% 3,194 - 27.6% 3,148 - 30.3% 3,017 - 20.8% 2,909 - 15.2% 2,799 - 16.4% 2,727 - 13.8% 2,659 - 15.3% 2,653 - 12.9% 2.582 - 11.5% 2,506 - 14.8% 2,331 - 13.1% 2,287 - 14.3% 2,226 - 13.7% 2,145 - 12.0% 2.088 - 12.9% 2.033 - 15.4% 1.939 - 12.9% 1,867 - 10.2% 1,834 - 9.5% 1,826 - 11.0% .2. A process for preparing an anhydrous crystalline γ-modification for n. 1, characterized in that the dissolved in an organic solvent, separated crystallites of organic solvent followed by filtration, washing and freeze drying, and then subjected to heat treatment at temperatures from 70 to 125 ° C for 20-40 p.3. A method according to. 2, characterized in that freeze drying is carried out at temperatures: the capacitor (-48) - (-56) ° C on the product of (-10) - (+ 30) ° C and residual pressure in the chamber (9-5) · 10Torr for 22-26 p.4. Use of crystalline anhydrous γ-modification according to Claim. 1 for the preparation of a pharmaceutical formulation as a selective inhibitor of tyrosine kinases for the treatment of cancer, comprising a therapeutically effective amount of crystalline anhydrous γ-Modifying the1. Кристаллическая безводная γ-модификация 4-(3′-хлор-4′-фторанилино)-7-метокси-6-(3-морфолинопропокси)хиназолина, характеризующаяся следующим набором межплоскостных расстояний (d, Å) и соответствующих им интенсивностей (Iотн., %): 13,786 - 84,0% 12,569 - 53,6% 10,789 - 17,4% 10,659 - 13,2% 9,513 - 14,3% 8,284 - 12,4% 7,914 - 28,1% 7,171 - 29,6% 6,840
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