Crystalline form of Bimatoprost, preparation method and use thereof

• US 8,664,275 B2
• Filed: 07/30/2010
• Issued: 03/04/2014
• Est. Priority Date: 11/02/2009
• Status: Active Grant

• Current Assignee: Shanghai Techwell Biopharmaceutical Co., Ltd.
• Original Assignee: Shanghai Techwell Biopharmaceutical Co., Ltd.
• Inventors: He, Bingming, Tang, Zhijun, Zhuo, Zhonghao, Zheng, Yunman, Gao, Xiaoliang, Ji, Xiaoming
• Primary Examiner(s): SHIAO, REI TSANG
• Application Number:
  US13/505,360
• Publication Number:
  US 20120270946A1
• Time in Patent Office: 1,313 Days
• Field of Search: 514/622, 564/171
• US Class Current: 514/622
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 405/00 Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof

Abstract

The crystalline form A of Bimatoprost of formula I, its preparation method and use are provided. There are characteristic peaks where diffraction angles 2θ are 3.2±0.2°, 5.5±0.2°, 11.4±0.2°, 16.7±0.2°, 17.6±0.2°, 19.9±0.2°, 20.8±02° and 22.8±0.2° in the X-ray powder diffraction pattern of the crystalline form A.

Claims

1. A crystalline form A of Bimatoprost, having a structure as shown in formula I, wherein the characteristic peaks at the diffraction angles 2θ

are 3.2±

0.2°

, 19.9±

0.2°

, 20.8±

0.2° and

22.8±

0.2°

in an X-ray powder diffraction (XRPD) pattern of the crystalline form A;

2. The crystalline form A of Bimatoprost according to claim 1, characterized in that there are further characteristic peaks where diffraction angles 2θ

are 5.5±

0.2°

, 11.4±

0.2°

, 16.7±

0.2° and

17.6±

0.2°

in the X-ray powder diffraction (XRPD) pattern of the crystalline form A.

3. The crystalline form A of Bimatoprost according to claim 2, characterized in that there are further characteristic peaks where diffraction angles 2θ

are 6.3±

0.2°

, 8.3±

0.2°

, 9.5±

0.2°

, 10.9±

0.2°

, 12.6±

0.2°

, 13.8±

0.2°

, 18.4±

0.2°

, 19.0±

0.2°

, 21.7±

0.2°

, 23.9±

0.2°

, 26.2±

0.2°

, 27.7±

0.2°

, 28.3±

0.2°

, 30.4±

0.2°

, 32.4±

0.2° and

35.3±

0.2°

in the X-ray powder diffraction (XRPD) pattern of the crystalline form A.

4. The crystalline form A of Bimatoprost according to claim 1, characterized in that there are characteristic peaks where diffraction angles 2θ

±

0.1°

are 19.9, 20.8 and 22.8 in the X-ray powder diffraction (XRPD) pattern of the crystalline form A.

5. The crystalline form A of Bimatoprost according to claim 4, characterized in that 3.2, 5.5, 11.4, 16.7 and 17.6 in the X-ray powder diffraction (XRPD) pattern of the crystalline form A.

6. The crystalline form A of Bimatoprost according to claim 5, characterized in that there are characteristic peaks where diffraction angles 2θ

±

0.1°

are 6.3, 8.3, 9.5, 10.9, 12.6, 13.8, 18.4, 19.0, 21.7, 23.9, 26.2, 27.7, 28.3, 30.4, 32.4 and 35.3 in the X-ray powder diffraction (XRPD) pattern of the crystalline form A.

7. The crystalline form A of Bimatoprost according to claim 1, characterized in that the crystalline form A has the maximum peak value at 66.5-70.5°

C. in differential scanning calorimetry (DSC).

8. The crystalline form A of Bimatoprost according to claim 1, characterized in that the crystalline form A has the differential scanning calorimetry (DSC) as shown in FIG. 3.

9. The crystalline form A of Bimatoprost according to claim 1, characterized in that the crystalline form A has an infrared spectrum as shown in FIG. 4.

10. A preparation method of the crystalline form A of Bimatoprost Bimatoprost according to claim 1, characterized in that the method comprises the steps of:

(1) mixing oily Bimatoprost as shown in formula I with one solvent selected from the following solvents to obtain solution 1;

acetone, butanone, methyl acetate, ethyl acetate, isopropyl acetate, tert-butyl acetate, dichloromethane and isopropanol;

(2) mixing the solution 1 with a non-polar solvent to obtain solution 2; and

(3) stirring the solution 2 to obtain the crystalline form A of Bimatoprost;

wherein the non-polar solvent is selected from one of or a mixture of more of the following;

pentane, hexane, heptane and petroleum ether.

11. The preparation method according to claim 10, characterized in that the mixing temperature is 10-30°

C. in step (1).

12. The preparation method according to claim 10, characterized in that the stirring time is 1-50 h in step (2).

13. The preparation method according to claim 10, characterized in that the stirring temperature is −

25°

C. to 10°

C. in step (3).

14. The preparation method according to claim 13, characterized in that the stirring temperature is −

25°

C., −

10°

C., 0°

C., 5°

C. or 10°

C. in step (3).

15. The preparation method according to claim 10, characterized in that the mixing ratio of a compound Bimatoprost as shown in formula I to the solvent is 1:

5-100 to obtain the solution 1 in step (1).

16. The preparation method according to claim 10, characterized in that the mixing ratio of the solution 1 to the non-polar solvent is 0.3-2:

1 in step (2).

17. The preparation method according to claim 10, characterized in that the oily Bimatoprost in step (1) is obtained by the following steps:

mixing the Bimatoprost as shown in formula I with an alcoholic solvent and then concentrating the mixture to dryness to obtain the oily Bimatoprost;

wherein the alcoholic solvent is C1-C4 linear or branched alkyl alcohol.

18. A method of treating glaucoma comprising the step of:

administering a pharmaceutical composition including the crystalline form A of Bimatoprost according to claim 1 combined with a pharmaceutically acceptable carrier in an amount effective for treating glaucoma.

19. A preparation method of a pharmaceutical composition, characterized in that the method comprises the step of:

mixing the crystalline form A of Bimatoprost according to claim 1 with a pharmaceutically acceptable carrier to obtain a pharmaceutical composition.