Tranilast compositions and cocrystals

• US 10,150,729 B2
• Filed: 10/26/2017
• Issued: 12/11/2018
• Est. Priority Date: 03/30/2012
• Status: Active Grant

• Current Assignee: Nuformix Limited (Nuformix Plc)
• Original Assignee: Nuformix Technologies Ltd. (Nuformix Plc)
• Inventors: Holland, Joanne, Frampton, Christopher
• Primary Examiner(s): Katakam, Sudhakar
• Application Number:
  US15/794,530
• Publication Number:
  US 20180118662A1
• Time in Patent Office: 411 Days
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07C 229/56 with amino and carboxyl groups bound in ortho-position
• CPC Class Codes: C07C 229/60 with amino and carboxyl groups bound in meta- or para- positions
• CPC Class Codes: C07C 233/55 having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton
• CPC Class Codes: C07C 235/38 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 275/02 Salts; Complexes; Addition compounds
• CPC Class Codes: C07C 65/03 monocyclic and having all hydroxy or O-metal groups bound to the ring
• CPC Class Codes: C07C 65/05 o-Hydroxy carboxylic acids
• CPC Class Codes: C07C 65/10 Salicylic acid
• CPC Class Codes: C07D 213/82 in position 3
• CPC Class Codes: C07D 275/06 with hetero atoms directly attached to the ring sulfur atom

Abstract

New tranilast complexes and new tranilast cocrystals are disclosed. These include a 1:1 tranilast nicotinamide complex, a 1:1 tranilast nicotinamide cocrystal, a 1:1 tranilast saccharin complex, a 1:1 tranilast saccharin cocrystal, a 1:1 tranilast gentisic acid complex, a 1:1 tranilast gentisic acid cocrystal, a 1:1 tranilast salicylic acid complex, a 1:1 tranilast salicylic acid cocrystal, a 1:1 tranilast urea complex, a 1:1 tranilast urea cocrystal, a 1:1 tranilast 4-aminobenzoic acid complex, a 1:1 tranilast 4-aminobenzoic acid cocrystal, a 1:1 tranilast 2,4-dihydroxybenzoic acid complex and a 1:1 tranilast 2,4-dihydroxybenzoic acid cocrystal. Also disclosed are pharmaceutical compositions containing a tranilast complex or cocrystal of the invention and a pharmaceutically acceptable carrier. Methods of treatment using the tranilast complexes and cocrystals as well as the pharmaceutical compositions are disclosed.

Claims

1. A tranilast cocrystal selected from the group consisting of a 1:

1 tranilast gentisic acid cocrystal, a 1;

1 tranilast salicylic acid cocrystal, a 1;

1 tranilast urea cocrystal, a 1;

1 tranilast 4-aminobenzoic acid cocrystal, and a 1;

1 tranilast 2,4-dihydroxybenzoic acid cocrystal,

wherein the 1;

1 tranilast gentisic acid cocrystal is characterized by at least one of;

a powder X-ray diffraction pattern having at least three peaks selected from 7.4, 10.5, 12.2, 14.8, 15.7, and 26.4 °

2θ

±

0.2°

2θ

;

or a powder X-ray diffraction pattern substantially similar to FIG. 12;

wherein the 1;

1 tranilast salicylic acid cocrystal is characterized by at least one of;

a powder X-ray diffraction pattern having at least three peaks selected from 4.4, 10.4, 13.1, 16.9 and 18.5 °

2θ

±

0.2°

2θ

;

or a powder X-ray diffraction pattern substantially similar to FIG. 16;

wherein the 1;

1 tranilast urea cocrystal is characterized by at least one of;

a powder X-ray diffraction pattern having at least three peaks selected from 8.2, 11.3, 13.8, 15.0, 16.3 and 25.3 °

2θ

±

0.2°

2θ

;

or a powder X-ray diffraction pattern substantially similar to FIG. 20;

wherein the 1;

1 tranilast 4-aminobenzoic acid cocrystal is characterized by at least one of;

a powder X-ray diffraction pattern having at least three peaks selected from 5.4, 6.7, 11.5, 12.0, 16.4 and 17.9 °

2θ

±

0.2°

2θ

;

or a powder X-ray diffraction pattern substantially similar to FIG. 24; and

wherein the 1;

1 tranilast 2,4-dihydroxybenzoic acid cocrystal is characterized by at least one of;

a powder X-ray diffraction pattern having at least three peaks selected from 3.9, 7.9, 11.8, 12.6 and 15.4 °

2θ

±

0.2°

2θ

;

or a powder X-ray diffraction pattern substantially similar to FIG. 28.

2. A pharmaceutical composition comprising a tranilast cocrystal of claim 1 and a pharmaceutically acceptable carrier.

3. A pharmaceutical composition of claim 2, wherein the composition is a topical formulation.

4. A pharmaceutical composition of claim 2, wherein the composition is an inhalable formulation.

5. A method of preparing a liquid pharmaceutical composition comprising the step of dissolving a tranilast cocrystal of claim 1 in a pharmaceutically acceptable solvent.

6. A pharmaceutical composition of claim 2, wherein the composition is an oral formulation.

7. A pharmaceutical composition of claim 1, prepared by dissolving the tranilast cocrystal in a pharmaceutically acceptable solvent.

8. A pharmaceutical composition of claim 7, wherein the composition is an injectable formulation.

9. The tranilast cocrystal of claim 1, wherein the tranilast cocrystal is the 1:

1 tranilast gentisic acid cocrystal.

10. The tranilast cocrystal of claim 1, wherein the tranilast cocrystal is the 1:

1 tranilast salicylic acid cocrystal.

11. The tranilast cocrystal of claim 1, wherein the tranilast cocrystal is the 1:

1 tranilast urea cocrystal.

12. The tranilast cocrystal of claim 1, wherein the tranilast cocrystal is the 1:

1 tranilast 4-aminobenzoic acid cocrystal.

13. The tranilast cocrystal of claim 1, wherein the tranilast cocrystal is the 1:

1 tranilast 2,4-dihydroxybenzoic acid cocrystal.