Crystalline form of nicotinamide riboside

• US 10,323,058 B2
• Filed: 07/24/2015
• Issued: 06/18/2019
• Est. Priority Date: 07/24/2014
• Status: Active Grant

• Current Assignee: W R Grace & Company - CONN (WR Grace & Company)
• Original Assignee: W R Grace & Company - CONN (WR Grace & Company)
• Inventors: Carlson, Erik C., Standen, Michael C., Morrill, Westin M.
• Primary Examiner(s): Berry, Layla D
• Application Number:
  US15/328,664
• Publication Number:
  US 20170210774A1
• Time in Patent Office: 1,425 Days
• Field of Search: None
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07H 19/048 Pyridine radicals

Abstract

Provided are crystalline forms of nicotinamide riboside, including a Form I of nicotinamide riboside chloride according to formula (I). Also disclosed are pharmaceutical compositions comprising the crystalline Form I of nicotinamide riboside chloride, and methods of producing such pharmaceutical compositions. In other aspects, the present disclosure pertains to methods comprising administering to a subject the crystalline Form I of nicotinamide riboside chloride. The present disclosure also provides methods of preparing the crystalline Form I of nicotinamide riboside chloride. Also provided are a crystalline Form I of nicotinamide riboside chloride that is prepared according to any of the disclosed methods for preparing the crystalline Form I.

Claims

1. A crystalline Form I of nicotinamide riboside chloride according to formula I

2. The crystalline Form I according to claim 1 that is characterized by a powder X-ray diffraction pattern substantially as shown in FIG. 1.

3. The crystalline Form I according to claim 1 that is characterized by a powder X-ray diffraction pattern having peaks substantially as shown in Table 1±

0.2 degrees two theta.

4. The crystalline Form I according to claim 1 that is characterized by an IR spectrum having peaks at 671.7, 1035.6, and 1061.8 cm⁻

1±

0.2 cm<sup>−

1</sup>.

5. The crystalline Form I according to claim 1 that is characterized by an IR spectrum substantially as shown in FIG. 2.

6. The crystalline Form I according to claim 1 that is characterized by an IR spectrum having peaks substantially as shown in Table 2±

0.2 cm<sup>−

1</sup>.

7. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram substantially as shown in FIG. 4.

8. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 10 K/min comprising an endothermic event with an onset temperature of 119°

C.±

2°

C., an endothermic event with a peak temperature of 123°

C.±

2°

C., or both.

9. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 1 K/min comprising an endothermic event with an onset temperature of 104°

C.±

2°

C., a peak temperature of 108°

C.±

2°

C., or both.

10. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 2 K/min comprising an endothermic event with an onset temperature of 109°

C.±

2°

C., a peak temperature of 113°

C.±

2°

C., or both.

11. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 5 K/min comprising an endothermic event with an onset temperature of 114°

C.±

2°

C., a peak temperature of 118°

C.±

2°

C., or both.

12. The crystalline Form I according to claim 1 that is further characterized by a DSC thermogram obtained using a heating rate of 20 K/min comprising an endothermic event with an onset temperature of 122°

C.±

2°

C., a peak temperature of 128°

C.±

2°

C., or both.

13. The crystalline Form I according to claim 1 that is further characterized by a TGA/SDTA thermogram substantially as shown in FIG. 7A.

14. The crystalline Form I according to claim 1 that is further characterized by a TGA/SDTA thermogram comprising an endothermic event at 116°

C.±

2°

C. and a mass loss of about 0.4%.

15. The crystalline Form I according to claim 1 that is further characterized by a DVS change in mass plot substantially as shown in FIG. 8A.

16. The crystalline Form I according to claim 1 that is further characterized by a DVS isotherm plot substantially as shown in FIG. 8B.

17. The crystalline Form I according to claim 1 that is further characterized by a water vapor sorption isotherm showing a water uptake of not more than about 0.5 wt % at a relative humidity of up to 60%.

18. The crystalline Form I according to claim 1 that is further characterized by a water vapor sorption isotherm showing a water uptake of not more than about 1.0 wt %, at a relative humidity of up to 70%.

19. The crystalline Form I according to claim 1 wherein said crystalline Form I is anhydrous.

20. A method for increasing nicotinamide adenine dinucleotide (NAD) concentration in a subject in need thereof comprising administering to the subject a pharmaceutically acceptable amount of the crystalline Form I according to claim 1.

21. The method according to claim 20 wherein said crystalline Form I is administered to said subject in a composition that further comprises a pharmaceutically acceptable excipient.

22. The method according to claim 20 wherein said administration provides increased insulin sensitivity, enhancement of sirtuin function, improved mitochondrial health or function, increased production of mitochondria, or neuroprotection.

23. A method for supplementing the diet of a subject comprising administering to the subject a pharmaceutically acceptable amount of the crystalline Form I according to claim 1.