DNP and DNP prodrug treatment of neuromuscular, neurodegenerative, autoimmune, developmental, traumatic brain injury, concussion, dry eye disease, hearing loss and/or metabolic diseases

Patent metadata

Field	Value
Publication number	US-10548900-B2
Application number	US-201715451938-A
Country	US
Kind code	B2
Filing date	Mar 7, 2017
Priority date	Mar 7, 2016
Publication date	Feb 4, 2020
Grant date	Feb 4, 2020

Abstract

A composition and method of treatment of neuromuscular, neuromuscular degenerative, neurodegenerative, autoimmune, developmental, traumatic, hearing loss related, and/or metabolic diseases, including spinal muscular atrophy (SMA) syndrome (SMA1, SMA2, SMA3, and SMA4, also called Type I, II, III and IV), traumatic brain injury (TBI), concussion, keratoconjunctivitis sicca (Dry Eye Disease), glaucoma, Sjogren's syndrome, rheumatoid arthritis, post-LASIK surgery, anti-depressants use, Wolfram Syndrome, and Wolcott-Rallison syndrome. The composition is selected from the group consisting of 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP, bipartite 2,3-dinitrophenol, 2,4-dinitrophenol, 2,5-dinitrophenol, 2,6-dinitrophenol, 3,4-dinitrophenol, or 3,5-dinitrophenol (2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP) prodrugs; Gemini prodrugs, bioprecursor molecules, and combinations thereof. A dose of the composition for treatment of neurodegenerative diseases may be from about 0.01 mg/kg of body weight to about 50 mg/kg of body weight of the patient in need of treatment. A dose of the composition for treatment of metabolic diseases may be from about 1 mg/70 kg of body weight to about 100 mg/70 kg of body weight of the patient in need of treatment, and a maximum dose per day is about 200 mg/70 kg of body weight of the patient in need of treatment.

First claim

We claim:

1. A composition comprising a dinitrophenol prodrug having a formula selected from:

2. The composition of claim 1 , wherein the prodrug is stable at a pH of 1-2.

3. The composition of claim 1 , wherein the prodrug is stable at a pH of 4.5.

4. The composition of claim 1 , wherein the prodrug is stable at a pH of 5-9.

5. A composition comprising a 2,3-DNP, 2,4-DNP, 2,5-DNP, 2,6-DNP, 3,4-DNP, or 3,5-DNP “Gemini” prodrug represented by Formula VII:

6. The composition of claim 5 , wherein the prodrug is stable at a pH of 1-2.

7. The composition of claim 5 , wherein the prodrug is stable at a pH of 4.5.

8. The composition of claim 5 , wherein the prodrug is stable at a pH of 5-9.

9. A composition comprising a 2,4-DNP bioprecursor represented by Formula VIII or Formula IX:

10. The composition of claim 9 , wherein the bioprecursor is stable at a pH of 1-2.

11. The composition of claim 9 , wherein the bioprecursor is stable at a pH of 4.5.

12. The composition of claim 9 , wherein the bioprecursor is stable at a pH of 5-9.

13. The composition of claim 1 , wherein the dinitrophenol prodrug has the formula:

14. The composition of claim 1 , wherein the dinitrophenol prodrug has the formula:

15. The composition of claim 1 , wherein the dinitrophenol prodrug has the formula:

16. The composition of claim 1 , wherein the dinitrophenol prodrug has the formula:

17. The composition of claim 1 , wherein the dinitrophenol prodrug has the formula:

18. A depot nanoparticle formulation comprising a dinitrophenol prodrug having a formula selected from:

19. The depot nanoparticle formulation of claim 18 , wherein the prodrug is stable at a pH of 1-2.

20. The depot nanoparticle formulation of claim 18 , wherein the prodrug is stable at a pH of 4.5.

21. The depot nanoparticle formulation of claim 18 , wherein the prodrug is stable at a pH of 5-9.

Assignees

• Mitochon Pharmaceuticals Inc
• Bioventures Llc

Inventors

• Geisler John Gerard
• Alonso Robert
• Crooks Peter Anthony
• Penthala Narsimha Reddy
• Albayati Zaineb

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P27/16

  Otologicals · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61P27/04

  Artificial tears; Irrigation solutions · CPC title