SOLID DISPERSIONS CONTAINING AGENTS CAUSING APOPTOSIS Russian patent published in 2016 - IPC A61K31/437 A61K47/00 A61K9/14 C07D471/04 A61P35/00 

FIELD: medicine.

SUBSTANCE: invention relates to a solid dispersion for apoptosis induction. Dispersion contains a compound of formula I

,

where: R⁰ denotes chlorine; R¹ and R² denote H; R³ and R⁴ denote methyl; A¹ denotes N and A² denotes CH; R⁵ denotes nitro; X denotes -NH-; Y denotes -(CH₂)_n-, where n=1; and R⁶ is selected from a group consisting of tetrahydropyranyl and 4-hydroxy-4-methylcyclohexyl; or its pharmaceutically acceptable salt. Herewith the compound of formula I or its pharmaceutically acceptable salt are dispersed in a solid matrix, which contains (a) at least one pharmaceutically acceptable water-soluble polymer carrier and (b) at least one pharmaceutically acceptable surfactant. Water-soluble polymer carrier is selected from a group consisting of homopolymers and copolymers of N-vinillactams, cellulose esters, cellulose ethers, polyalkylene oxides with high molecular weight, polyacrylates, polymethacrylates, polyacrylamides, vinyl acetate polymers, grafted copolymers of ethylene glycol, polyvinyl caprolactam and polyvinyl acetate, oligo- and polysaccharides and mixtures thereof. Surfactant is selected from a group consisting of polyoxyethylene glycerides, monoesters of sorbitan fatty acids, polysorbates, α-tocopheryl-polyethylene glycol succinate (TPGS) and their mixtures. Also not more than 5 % of the compound of formula I or its pharmaceutically acceptable salt in a solid dispersion is in crystalline form as per X-ray diffraction analysis data. Also described are: a method of producing the solid dispersion, orally delivered pharmaceutical dosage form.

EFFECT: solid dispersion is suitable for oral use by a person who needs it for treating a disease characterized by overexpression of one or more antiapoptosis proteins from the Bcl-2 family, for example, cancer.

44 cl, 2 tbl, 17 ex