Dapagliflozin crystal form and preparation method and use thereof

Patent metadata

Field	Value
Publication number	US-10464915-B2
Application number	US-201716302332-A
Country	US
Kind code	B2
Filing date	May 22, 2017
Priority date	May 24, 2016
Publication date	Nov 5, 2019
Grant date	Nov 5, 2019

Abstract

Disclosed are a new dapagliflozin crystal form and a preparation method and use thereof. In particular, disclosed are a crystal form E of 2-chloro-5-(β-D-glucopyranose-1-yl)-4′-ethyoxyldiphenylmethane and a preparation method therefor, and a pharmaceutical composition containing a therapeutically effective amount of the crystal form and the use thereof in treating type II diabetes.

First claim

What is claimed is:

1. Crystal form E of dapagliflozin, wherein the crystal form E is characterized by an X-ray powder diffraction spectrum comprising diffraction peaks at angles 2θ of 3.5±0.2, 4.1±0.2, 5.1±0.2, 7.3±0.2, 14.0±0.2, and 14.8±0.2, 19.1±0.2, and 21.8±0.2.

2. The crystal form E of dapagliflozin according to claim 1 , wherein the X-ray powder diffraction spectrum comprises diffraction peaks at angles 2θ of 3.5±0.2, 4.1±0.2, 5.1±0.2, 6.6±0.2, 7.3±0.2, 8.0±0.2, 9.0±0.2, 9.4±0.2, 10.3±0.2, 10.9±0.2, 13.0±0.2, 14.0±0.2, 14.8±0.2, 15.7±0.2, 16.5±0.2, 18.2±0.2, 19.1±0.2, 21.0±0.2, and 21.8±0.2.

3. The crystal form E of dapagliflozin according to claim 1 , wherein the X-ray powder diffraction spectrum is substantially as shown in FIG. 1 .

4. A preparation method for crystal form E of dapagliflozin, comprising:
1)(a) placing dapagliflozin in an ester solvent or a mixed solvent of an ester solvent and other solvent to form a solution;
2) saturating the solution by cooling or addition of a poor solvent or by both cooling and addition of a poor solvent;
3)(c) adding a seed crystal, stirring the solution to precipitate a solid and filtering the solid; and
4)(d) converting the solid to crystal form E by solvent removal.

5. The preparation method according to claim 4 , wherein a mass-to-volume ratio of dapagliflozin to the ester solvent in step (a) is 1:2 to 10.

6. The preparation method according to claim 4 , wherein the ester solvent in step (a) is an ester solvent having 2 to 6 carbon atoms.

7. The preparation method according to claim 4 , wherein a mass-to-volume ratio of dapagliflozin to the poor solvent in step (b) is 1:20 to 70.

8. The preparation method according to claim 4 , wherein the poor solvent in step (b) is a liquid alkane solvent or an ether solvent.

9. The preparation method according to claim 4 , wherein the solvent removal in step (d) is carried out under vacuum and heating conditions.

10. The preparation method according to claim 4 , wherein the solvent removal in step (d) is carried out at a temperature of 25° C. to 80° C.

11. A pharmaceutical composition comprising an effective amount of the crystal form E of dapagliflozin according to claim 1 and one or more pharmaceutically acceptable excipients.

12. A method for treating type II diabetes I in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition according to claim 11 .

13. The preparation method according to claim 5 , wherein the mass-to-volume ratio of dapagliflozin to the ester solvent in step (a) is 1:2.5 to 10.

14. The preparation method according to claim 5 , wherein the mass-to-volume ratio of dapagliflozin to the ester solvent in step (a) is 1:4 to 5.

15. The preparation method according to claim 6 , wherein the ester solvent has 3 to 5 carbon atoms.

16. The preparation method according to claim 6 , wherein the ester solvent is ethyl formate, ethyl acetate or n-propyl acetate.

17. The preparation method according to claim 7 , wherein the mass-to-volume ratio of dapagliflozin to the poor solvent in step (b) is 1:30 to 40.

18. The preparation method according to claim 8 , wherein the poor solvent is a liquid alkane solvent.

19. The preparation method according to claim 18 , wherein the liquid alkane solvent is n-hexane, n-heptane or n-octane.

20. The preparation method according to claim 4 , wherein the solvent removal in step (d) is carried out at a temperature of 50° C. to 60° C.

Assignees

• Jiangsu Hansoh Pharmaceutical Group Co Ltd

Inventors

• Li Xiang
• He Lei
• Yu Jun
• Wang Jinjia
• Du Zuyin

Classifications

• A61K31/351

  not condensed with another ring · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C07H7/04 Primary

  Carbocyclic radicals · CPC title

• C07D309/10 Primary

  Oxygen atoms · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title