TIANEPTINE OXALATE SALTS AND POLYMORPHS

• US 20180338984A1
• Filed: 12/28/2017
• Published: 11/29/2018
• Est. Priority Date: 12/28/2016
• Status: Active Grant

• Current Assignee: Tonix pharma holdings limited (Tonix Pharmaceuticals Holding Corp.)
• Original Assignee: Tonix pharma holdings limited (Tonix Pharmaceuticals Holding Corp.)
• Inventors: Giaffreda, Stefano Luca, Modena, Enrico, Fabbroni, Serena, Chiarucci, Michel, Edgar, Mark T.
• Granted Patent: US 10,449,203 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07D 281/02 Seven-membered rings

Abstract

Disclosed herein is an oxalate salt/co-crystal (tianeptine oxalate) of (RS)-7-(3-chloro-6-methyl-6,11-dihydrodibenzo[c,f][1,2]thiazepin-11-ylamino)heptanoic acid S,S-dioxide (tianeptine) as shown in Formula I:

Claims

1. An oxalate salt/co-crystal (tianeptine oxalate) of (RS)-7-(3-chloro-6-methyl-6,11-dihydrodibenzo[c,f][1,2]thiazepin-11-ylamino)heptanoic acid S,S-dioxide (tianeptine) as shown in Formula I:

2. The salt/co-crystal of claim 1, wherein the tianeptine oxalate is crystalline.

3. The salt/co-crystal of claim 2, wherein the salt is a mixture of crystalline tianeptine hemi-oxalate Form A salt and tianeptine mono-oxalate Form A, tianeptine mono-oxalate Form B, or a combination thereof.

4. The salt/co-crystal of claim 2, wherein the salt is anhydrous crystalline tianeptine hemi-oxalate Form A, tianeptine mono-oxalate Form A, tianeptine mono-oxalate Form B, or a combination thereof.

7. The anhydrous crystalline tianeptine hemi-oxalate Form A of claim 4, wherein the crystalline form exhibits an X-ray diffraction pattern (XRPD) comprising at least one peak at about 8.2, 8.6, 9.1, and 9.5 degrees 2θ

.

8. The compound of claim 7, wherein the tianeptine hemi-oxalate crystalline Form A exhibits an XRPD pattern further comprising at least one peak selected from the group consisting of about 4.5, 8.2, 8.6, 9.1, 9.5, 11.5, 14.2, 15.2, 15.8, 16.4, 19.2, 22.1, 23.9, 26.9, and 27.4 degrees 2θ

.

9. The anhydrous tianeptine hemi-oxalate crystalline Form A of claim 4, wherein the crystalline Form A exhibits an XRPD pattern substantially the same as FIG. 2.

10. The anhydrous crystalline tianeptine hemi-oxalate Form A of claim 4, characterized by at least one of:

(a) an XPRD pattern exhibiting at least four of the peaks shown in FIG. 2;

(b) an FT-IR spectrum substantially the same as FIG. 5; and

(c) an NMR spectrum substantially the same as FIG. 6.

11. The anhydrous crystalline tianeptine mono-oxalate of claim 4, wherein the crystalline form exhibits an X-ray diffraction pattern (XRPD) comprising at least one peak at about 10.2 and 10.5 degrees 2θ

.

12. The compound of claim 11, wherein the crystalline form exhibits an XRPD pattern further comprising at least one peak selected from the group consisting of about 7.5, 8.3, 10.2, 10.5, 11.9, 14.7, 16.2, 16.3, 17.9, 18.7, 21.0, 21.7, and 22.1 degrees 2θ

.

13. The anhydrous crystalline tianeptine mono-oxalate Form A of claim 4, wherein the crystalline form exhibits an XRPD pattern substantially the same as FIG. 10.

14. The anhydrous crystalline tianeptine mono-oxalate Form A of claim 4, characterized by an XPRD pattern exhibiting at least four of the peaks shown in FIG. 10.

15. The anhydrous tianeptine oxalate crystalline form of claim 4, wherein the crystalline form is tianeptine hemi-oxalate Form A and tianeptine mono-oxalate Form A.

16. The anhydrous tianeptine oxalate crystalline form of claim 15, wherein the crystalline form exhibits an XRPD pattern comprising at least one peak selected from the group consisting of about 10.2 and 10.5 degrees 2θ

.

17. The compound of claim 16, wherein the crystalline form exhibits an XRPD pattern further comprising at least one peak selected from the group consisting of about 7.5, 8.3, 10.2, 10.5, 11.9, 14.7, 16.2, 16.3, 17.9, 18.7, 21.0, 21.7, and 22.1 degrees 2θ

.

18. The anhydrous crystalline tianeptine oxalate form of claim 15, wherein the crystalline form exhibits an XRPD pattern substantially the same as FIG. 9.

19. The anhydrous tianeptine oxalate crystalline form of claim 4, wherein the crystalline form is tianeptine mono-oxalate Form B.

20. The anhydrous crystalline tianeptine oxalate form of claim 19, wherein the crystalline form exhibits an XRPD pattern substantially the same as FIG. 14.

22. The co-crystal of claim 3, wherein the co-crystal is a mixture of crystalline tianeptine hemi-oxalate Form A salt and tianeptine mono-oxalate Form A, tianeptine mono-oxalate Form B, or a combination thereof.

23. The co-crystal of claim 4, wherein the co-crystal is anhydrous crystalline tianeptine hemi-oxalate Form A, tianeptine mono-oxalate Form A, tianeptine mono-oxalate Form B, or a combination thereof.

5. A pharmaceutical composition comprising the salt/co-crystal of tianeptine oxalate with a pharmaceutically acceptable carrier, diluent or excipient.

6. The pharmaceutical composition of claim 5, wherein the salt/co-crystal is anhydrous crystalline tianeptine hemi-oxalate Form A, mono-oxalate Form A, or a combination thereof.

21. The pharmaceutical composition of claim 6, wherein the composition is in a solid form, a liquid form, a suspension form, a sustained release form, a delayed release form, or an extended release form.