NANO-AMORPHOUS FORM (RS)-3-(4-AMINO-1-OXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)PIPERIDINE-2,6-DIONE (VERSIONS), A METHOD FOR PRODUCTION THEREOF AND USE FOR TREATING IMMUNOLOGICAL OR ONCOLOGICAL DISEASES
Obshchestvo s ogranichennoi otvetstvennost'yu «Aksel'Farm»
发明人:
Torchinov Georgij Yur'evich (RU),Торчинов Георгий Юрьевич (RU)
申请号：
RU2020100184
公开号：
RU0002723624C1
申请日:
2019.12.31
申请国别(地区):
RU
年份:
2020
代理人:
摘要：
FIELD: chemistry.SUBSTANCE: invention relates to a nanoamorphous form of (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione, a method for production thereof and use in pharmaceutical compositions, which can be used for treating immunological and/or oncological diseases. Amorphous form of (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione is characterized by average particle size of 63.85±10 nm, glass transition temperature of 122.9±7 °C, crystallisation at temperature of 172.6±5 °C with specific thermal effect of 85.77±9 J/g and melting at temperature of 267.5±5 °C with specific heat effect of 149.8±15 J/g under conditions of differential scanning calorimetry at heating rate of 10 °C/min. Method of producing amorphous form of (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione involves the following steps: loading (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione into a melt consisting of 40 or 20 g of D-fructose, 15 or 7.5 glactose monohydrate and 40 or 20 g urea at 55 °C； stirring at temperature of 55 °C； adding the obtained melt into water cooled to +7 °C； mixing； filtering the precipitate； preparation of suspension in water； stirring at temperature of 20 °C for about 1 hour； filtration； washing the precipitate with water on filter； drying to constant weight under vacuum at temperature of + 40 °C. Used at stage of loading into melt (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione is obtained by reduction of 3-(4-nitro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione with gray cast iron in the form of a chipped fraction in 50 % aqueous ethanol in the presence of hydrochloric acid.EFFECT: amorphous form of (RS)-3-(4-amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione is intended for treating immunological or oncological diseases.6 cl, 10 dwg, 11 exИзобретение относится к наноаморфной форме (RS)-3-(4-амино-1-оксо-1,3-дигидро-2Н-изоиндол-2-ил)пи
