Nonracemic mixtures and uses thereof

• US 10,660,875 B1
• Filed: 01/09/2020
• Issued: 05/26/2020
• Est. Priority Date: 12/05/2017
• Status: Active Grant

• Current Assignee: Sunovion Pharmaceuticals Inc. (Sumitomo Chemical Company Limited)
• Original Assignee: Sunovion Pharmaceuticals Inc. (Sumitomo Chemical Company Limited)
• Inventors: Hopkins, Seth Cabot, Koblan, Kenneth Stephen, Snoonian, John R., Wilkinson, Harold Scott
• Primary Examiner(s): Badio, Barbara P
• Application Number:
  US16/738,261
• Publication Number:
  US 20200147040A1
• Time in Patent Office: 138 Days
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61P 25/24 Antidepressants

Abstract

Provided are compositions comprising unequal mixtures of (R)-amisulpride and (S)-amisulpride, or pharmaceutically acceptable salts thereof, where the amount of (R)-amisulpride is greater than the amount of (S)-amisulpride, compositions and medicaments comprising the same used for the treatment of various diseases and disorders, and methods of using same for the treatment of various diseases and disorders, including, but not limited to, dosage regimens. In addition, provided are various formulations thereof, including, but not limited to, formulations employing polymorphs of enantiomeric amisulpride.

Claims

1. A composition comprising:

(R)-(+)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base; and

(S)-(−

)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base;

wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg to about 600 mg by weight of free base; and

wherein the enantiomeric ratio of (R)-(+)-amisulpride to (S)-(−

)-amisulpride in the composition is 65;

35 to 88;

12 by weight of free base.

2. The composition of claim 1 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg to about 400 mg by weight of free base.

3. The composition of claim 1 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg by weight of free base.

4. The composition of claim 1 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 400 mg by weight of free base.

5. The composition of claim 1 wherein the composition comprises:

about 170 mg to about 340 mg of (R)-(+)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base; and

about 30 mg to about 60 mg (S)-(−

)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base.

6. The composition of claim 1 wherein the (R)-(+)-amisulpride is crystalline (R)-(+)-amisulpride of crystal Form A;

and the (S)-(−

)-amisulpride is crystalline (S)-(−

)-amisulpride of crystal Form A′

;

wherein Form A is characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.2°

, 9.7±

0.2, and 15.4±

0.2°

; and

Form A′

is characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.2°

, 9.7±

0.2, and 15.4±

0.2°

.

7. A composition comprising:

(R)-(+)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base; and

(S)-(−

)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base;

wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg to about 600 mg by weight of free base; and

wherein the enantiomeric ratio of (R)-(+)-amisulpride to (S)-(−

)-amisulpride in the composition is 65;

35 to 85;

15 by weight of free base.

8. The composition of claim 7 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg to about 400 mg by weight of free base.

9. The composition of claim 7 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg by weight of free base.

10. The composition of claim 7 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 400 mg by weight of free base.

11. The composition of claim 7 wherein the composition comprises:

about 170 mg to about 340 mg of (R)-(+)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base; and

about 30 mg to about 60 mg (S)-(−

)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base.

12. The composition of claim 7 wherein the (R)-(+)-amisulpride is crystalline (R)-(+)-amisulpride of crystal Form A;

and the (S)-(−

)-amisulpride is crystalline (S)-(−

)-amisulpride of crystal Form A′

;

wherein Form A is characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.2°

, 9.7±

0.2, and 15.4±

0.2°

; and

Form A′

is characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.2°

, 9.7±

0.2, and 15.4±

0.2°

.

13. A composition comprising:

(R)-(+)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base; and

(S)-(−

)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base;

wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg to about 600 mg by weight of free base; and

wherein the enantiomeric ratio of (R)-(+)-amisulpride to (S)-(−

)-amisulpride in the composition is 75;

25 to 85;

15 by weight of free base.

14. The composition of claim 13 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg to about 400 mg by weight of free base.

15. The composition of claim 13 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg by weight of free base.

16. The composition of claim 13 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 400 mg by weight of free base.

17. The composition of claim 13 wherein the composition comprises:

about 170 mg to about 340 mg of (R)-(+)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base; and

about 30 mg to about 60 mg (S)-(−

)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base.

18. The composition of claim 13 wherein the (R)-(+)-amisulpride is crystalline (R)-(+)-amisulpride of crystal Form A;

and the (S)-(−

)-amisulpride is crystalline (S)-(−

)-amisulpride of crystal Form A′

;

wherein Form A is characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.2°

, 9.7±

0.2, and 15.4±

0.2°

; and

Form A′

is characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.2°

, 9.7±

0.2, and 15.4±

0.2°

.

19. A composition comprising:

(R)-(+)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base; and

(S)-(−

)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base;

wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg to about 600 mg by weight of free base; and

wherein the enantiomeric ratio of (R)-(+)-amisulpride to (S)-(−

)-amisulpride in the composition is 80;

20 to 85;

15 by weight of free base.

20. The composition of claim 19 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg to about 400 mg by weight of free base.

21. The composition of claim 19 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 200 mg by weight of free base.

22. The composition of claim 19 wherein the combined amount of (R)-(+)-amisulpride and (S)-(−

)-amisulpride, or pharmaceutically acceptable salts thereof, is about 400 mg by weight of free base.

23. The composition of claim 19 wherein the composition comprises:

about 170 mg to about 340 mg of (R)-(+)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base; and

about 30 mg to about 60 mg (S)-(−

)-amisulpride, or a pharmaceutically acceptable salt thereof, by weight of free base.

24. The composition of claim 19, wherein the (R)-(+)-amisulpride is crystalline (R)-(+)-amisulpride of crystal Form A;

and the (S)-(−

)-amisulpride is crystalline (S)-(−

)-amisulpride of crystal Form A′

;

wherein Form A is characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.2°

, 9.7±

0.2, and 15.4±

0.2°

; and

Form A′

is characterized by a powder x-ray diffraction pattern comprising peaks, in terms of 2-theta, at 7.0±

0.2°

, 9.7±

0.2, and 15.4±

0.2°

.