Granted Patent B2

US 12,653,821 · App. 18/043,201 · Granted Jun 16, 2026

Inventors: Shuhuan Ying (Shanghai, CN); Zhixiang Chen (Shanghai, CN); Xian Zhang (Shanghai, CN); Tao Zhu (Shanghai, CN); Tingting Wang (Shanghai, CN)

Assignee: SHANGHAI BOCIMED PHARMACEUTICAL CO., LTD.

A61K31/495A61K9/0019A61K47/02A61K47/26A61K47/38A61K9/10C07B2200/13

Abstract

Claims (57)

1 . A pharmaceutical composition of cariprazine, comprising solid particles of cariprazine, wherein the solid particles of cariprazine have a particle size distribution of Dv(10) of ≤30 microns, Dv(50) of ≤50 microns, and Dv(90) of ≤100 microns, and

the solid particles of cariprazine are crystalline form A of cariprazine embonate having an X-ray powder diffraction pattern with characteristic peaks at 2θ values of 4.8°±0.2°, 13.1°±0.2°, 18.7°±0.2°, 20.1°±0.2°, 21.0°±0.2°, and 26.1°±0.2°.

2 . The pharmaceutical composition of cariprazine as claimed in claim 1 ,

wherein:

the X-ray powder diffraction pattern of the crystalline form A of cariprazine embonate has characteristic peaks at 2θ values of 4.8°±0.2°, 9.7±0.2°, 12.3°±0.2°, 13.1°±0.2°, 18.7°±0.2°, 20.1°±0.2°, 21.0°±0.2°, and 26.1°±0.2°.

3 . The pharmaceutical composition of cariprazine as claimed in claim 1 ,

wherein the composition is an injectable preparation that comprises one or more selected from a suspending agent, a wetting agent, an osmotic pressure regulator, a solvent, a stabilizer, a buffer, and a surfactant.

4 . The pharmaceutical composition of cariprazine as claimed in claim 3 ,

wherein the suspending agent is at a concentration in the range of 0 mg/mL to 10 mg/mL;

and/or, the suspending agent is one or more selected from sodium carboxymethylcellulose, methylcellulose, and polyvinylpyrrolidone.

5 . The pharmaceutical composition of cariprazine as claimed in claim 3 ,

wherein the wetting agent is at a concentration in the range of 1 mg/mL to 10 mg/ml;

and/or, the wetting agent is one or more selected from polysorbate 20, polysorbate 80, and poloxamer 188.

6 . The pharmaceutical composition of cariprazine as claimed in claim 3 ,

wherein: the osmotic pressure regulator is at a concentration in the range of 20 mg/mL to 30 mg/mL;

and/or,

the osmotic pressure regulator is selected from one or more of sodium chloride, mannitol and sucrose;

and/or,

the stabilizer is at a concentration in the range of 0 mg/mL to 30 mg/mL;

and/or,

the stabilizer is PVP K12;

and/or,

the buffer is selected from one or more of phosphoric acid, phosphate, citric acid, sodium citrate, hydrochloric acid and sodium hydroxide;

and/or,

the surfactant is sodium deoxycholate;

and/or,

the solvent is water for injection.

7 . The pharmaceutical composition of cariprazine as claimed in claim 3 ,

wherein the composition comprises:

cariprazine embonate,

sodium carboxymethylcellulose,

polysorbate20,

disodium phosphate,

monosodium phosphate,

mannitol,

and, optionally, sodium hydroxide or hydrochloric acid.

8 . The pharmaceutical composition of cariprazine as claimed in claim 7 , wherein the solid particles of cariprazine embonate are at a concentration of no less than 15 mg/mL.

9 . A preparation method for the pharmaceutical composition of cariprazine as claimed in claim 3 , comprising the following steps:

sequentially dissolving the wetting agent, the buffering agent and the osmotic pressure regulator in water for injection to obtain a mixture;

adding the solid particles of cariprazine embonate to the mixture to obtain an aqueous suspension of coarse particles;

grinding the aqueous suspension of coarse particles to obtain a suspension; and

adding the suspending agent to the suspension, adjusting pH of the suspension to 4.0-9.0 with sodium hydroxide or hydrochloric acid, and bringing the suspension to a predetermined volume to obtain the injectable preparation.

10 . A method for treating psychosis, bipolar disorder and/or acute mania, comprising administering the pharmaceutical composition of cariprazine as claimed in claim 1 to a patient in need thereof.

11 . The pharmaceutical composition of cariprazine as claimed in claim 1 ,

wherein Dv(90) of the solid particles ranges from 10 microns to 100 microns.

12 . The pharmaceutical composition of cariprazine as claimed in claim 4 ,

wherein the suspending agent is at a concentration in the range of 3.5 mg/mL to 5 mg/ml;

and/or, the suspending agent is carboxymethylcellulose.

13 . The pharmaceutical composition of cariprazine as claimed in claim 5 ,

wherein the wetting agent is at a concentration in the range of 1 mg/mL to 5 mg/mL;

and/or, the wetting agent is polysorbate 20.

14 . The pharmaceutical composition of cariprazine as claimed in claim 5 ,

wherein the osmotic pressure regulator is at a concentration in the range of 23 mg/mL to 26 mg/mL;

and/or, the stabilizer is at a concentration in the range of 1 mg/mL to 10 mg/mL.

15 . The pharmaceutical composition of cariprazine as claimed in claim 1 , wherein the solid particles of cariprazine have a particle size distribution of Dv(10) of 9.338 microns, Dv(50) of 27.446 microns and Dv(90) of 79.618 microns; or,

Dv(10) of 1.257 microns, Dv(50) of 4.794 microns and Dv(90) of 14.601 microns; or,

Dv(10) of 12.215 microns, Dv(50) of 26.987 microns and Dv(90) of 48.348 microns.

Assignments (2)

Priority Claims (4)

Continuity (1)

References Cited (29)