Crystals of thiadiazole derivative DPP-IV inhibitors and uses thereof

• US 10,450,328 B2
• Filed: 11/24/2016
• Issued: 10/22/2019
• Est. Priority Date: 11/27/2015
• Status: Active Grant

• Current Assignee: Centaurus Biopharma Co., Ltd., Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited)
• Original Assignee: Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (SINO Biopharmaceutical Limited)
• Inventors: Peng, Yan, Liu, Fei, Chen, Zhilin, Zhang, Yayu, Hu, Zhongyuan, Jiang, Jinfeng
• Primary Examiner(s): Chen, Po-Chih
• Application Number:
  US15/779,420
• Publication Number:
  US 20180334466A1
• Time in Patent Office: 1,062 Days
• Field of Search: None
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The present invention belongs to the field of drug crystals, relates to crystals of thiadiazole derivative DPP-IV inhibitors, and in particular relates to A and B type crystals of the compound as shown in formula 7. The crystals of the present invention have excellent stability. For example, under high temperature, high humidity or light test conditions, the material contents associated with the crystal of the compound of formula 7 do not change significantly. In addition, the crystal of the present invention also has a very good powder flowability and satisfies the requirements of drug preparation and production.

Claims

1. A crystalline Form A of a compound represented by Formula 7,

2. The crystalline Form A according to claim 1, further having additional diffraction peaks at about 8.67, 9.16, 9.55, 12.17, 12.98, 16.23, 18.15 and 18.91 degrees 2θ

.

3. The crystalline Form A according to claim 2, further having additional diffraction peaks at about 10.80, 14.35, 15.05, 15.64, 16.73, 17.31, 19.43, 20.23, 20.79, 21.36, 23.25, 23.96, 24.53, 25.05, 26.54, 28.43, 29.63 and 30.19 degrees 2θ

.

4. The crystalline Form A according to claim 1, having a powder X-ray diffraction pattern substantially as shown in FIG. 1.

9. A crystalline composition, comprising the crystalline Form A according to claim 1, wherein the crystalline Form A according to claim 1 accounts for 50% or more by weight of the crystalline composition.

10. The crystalline composition according to claim 9, wherein the crystalline Form A according to claim 1 accounts for 80% or more by weight of the crystalline composition.

11. The crystalline composition according to claim 9, wherein the crystalline Form A according to claim 1 accounts for 90% or more by weight of the crystalline composition.

12. The crystalline composition according to claim 9, wherein the crystalline Form A according to claim 1 accounts for 95% or more by weight of the crystalline composition.

13. A pharmaceutical composition, comprising the crystalline Form A according to claim 1, and pharmaceutically acceptable adjuvant(s).

15. A pharmaceutical composition, comprising the crystalline composition according to claim 9, and pharmaceutically acceptable adjuvant(s).

17. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the crystalline Form A according to claim 1;

wherein the disease is diabetes.

18. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the crystalline composition according to claim 9;

wherein the disease is diabetes.

19. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the pharmaceutical composition according to claim 13;

wherein the disease is diabetes.

5. A crystalline Form B of a compound represented by Formula 7,

6. The crystalline Form B according to claim 5, further having additional diffraction peaks at about 9.48, 17.16, 17.76, and 20.94 degrees 2θ

.

7. The crystalline Form B according to claim 6, further having additional diffraction peaks at about 12.54, 14.00, 14.68, 15.30, 18.16, 19.16, 19.58, 22.96, 24.76, 25.70, 26.44, 28.02, 28.96 and 29.38 degrees 2θ

.

8. The crystalline Form B according to claim 5, having a powder X-ray diffraction pattern substantially as shown in FIG. 2.

14. A crystalline composition, comprising the crystalline Form B according to claim 5, wherein the crystalline Form B according to claim 5 accounts for 50% or more by weight of the crystalline composition.

16. A pharmaceutical composition, comprising the crystalline Form B according to claim 5, and pharmaceutically acceptable adjuvant(s).

20. A method for treating a disease benefiting from DPP-IV inhibition, comprising administering to a subject in need thereof the crystalline Form B according to claim 5;

wherein the disease is diabetes.