SOLID DISPERSIONS PRODUCED BY MELT EXTRUSION AND CONTAINING APOPTOSIS-INDUCING AGENT Russian patent published in 2017 - IPC A61K9/14 A61K9/20 A61K31/496 A61K47/02 A61K47/06 A61K47/32 A61P35/02 A61P35/00 C07D471/04 

FIELD: pharmacology.

SUBSTANCE: dispersion includes a compound of Formula I , where the value of R⁰, R¹, R², R³, R⁴, A, B, R⁵, X, Y and R⁶ groups is determined in the claims, or a pharmaceutically acceptable salt thereof. 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. At least 5% of the compound of Formula I or its pharmaceutically acceptable salt is presented in the crystalline form, as studied by X-ray diffractometry. The compound or its pharmaceutically acceptable salt is presented in an amount equal to an amount of the parent compound from approximately 5% to approximately 40% by weight; at least one pharmaceutically acceptable water-soluble polymer carrier is presented in an amount from approximately 40% to approximately 85% by weight, and at least one pharmaceutically acceptable surfactant is presented in an amount from approximately 5% to approximately 20% by weight. A compound of Formula I in which R⁰ is chlorine, R¹ and R² are H, R³ and R⁴ are methyl, A is N, B is CH, R⁵ is nitro, X is -NH-, Y is - (CH₂)_n-, where n=1 , and R⁶ is selected from the group consisting of tetrahydropyranyl and 4-hydroxy-4-methylcyclohexyl, is excluded from the scope of the compound of Formula I. Methods for preparation of a solid dispersion suitable for oral delivery, a pharmaceutical dosage form and a solid dispersion for use as a medicament are also proposed.

EFFECT: solid dispersion is applicable for oral administration to the patient in need of treatment of a disease characterised by overexpression of one or more Bcl-2 family antiapoptotic proteins.

51 cl, 1 dwg, 17 tbl, 19 ex