Triple combination formulation for treatment of chronic pain

Patent metadata

Field	Value
Publication number	US-11219608-B2
Application number	US-201816209261-A
Country	US
Kind code	B2
Filing date	Dec 4, 2018
Priority date	Dec 4, 2017
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

The disclosure relates to use of a triple formulation comprising a histone deacetylase, a cyclodextrin and polyethylene glycol or propylene glycol, and in the treatment and management of chronic pain.

First claim

The invention claimed is:

1. A method of treating chronic pain in a subject in need thereof, the method comprising administering to the subject a composition comprising (i) a histone deacetylase (HDAC) inhibitor, (ii) a cyclodextrin or salt thereof, and (iii) polyethylene glycol (PEG) or propylene glycol, wherein the composition is provided in a therapeutically effective amount to treat the chronic pain with no metabolic toxicity,
wherein the HDAC inhibitor is vorinostat, wherein the cyclodextrin is 2-hydroxypropyl-b-cyclodextrin (HPBCD).

2. The method of claim 1 , wherein the polyethylene glycol (PEG) or propylene glycol is polyethylene glycol.

3. The method of claim 1 , wherein the composition comprises a molar ratio of HDAC inhibitor:cyclodextrin:PEG of about 1-100:1-1000:1-1000.

4. The method of claim 1 , wherein the HDAC inhibitor is present in an administration amount of about 0.1-500 mg/kg, cyclodextrin is present in an administration amount of about 1000-40,000 mg/kg, and the PEG is present in an amount of about 30-60% composition by weight.

5. The method of claim 1 , wherein the HDAC inhibitor is vorinostat at an administration amount of about 50 mg/kg, the cyclodextrin is HPBCD at an administration amount of at about 2000 mg/kg, and PEG is about 40-50% composition by weight.

6. The method of claim 1 , wherein the chronic pain comprises one or more of, chronic nociceptive pain, chronic neuropathic pain, chronic inflammatory pain, arthritis pain, fibromyalgia, breakthrough pain, persistent pain, hyperalgesia, allodynia, central sensitization, peripheral sensitization, disinhibition and augmented facilitation, or cancer pain.

7. A method of reducing or inhibiting one or more symptoms of chronic pain, the method comprising administering to the subject a composition comprising (i) a histone deacetylase (HDAC) inhibitor, (ii) a cyclodextrin or salt thereof, and (iii) polyethylene glycol (PEG) or propylene glycol, wherein the composition is provided in a therapeutically effective amount to reduce or inhibit one or more symptom of chronic pain with no metabolic toxicity,
wherein the HDAC inhibitor is vorinostat, wherein the cyclodextrin is 2-hydroxypropyl-b-cyclodextrin (HPBCD).

8. The method of claim 7 , wherein the polyethylene glycol (PEG) or propylene glycol is polyethylene glycol.

9. The method of claim 7 , wherein the composition comprises a molar ratio of HDAC inhibitor:cyclodextrin:PEG of about 1-100:1-1000:1-1000.

10. The method of claim 7 , wherein the HDAC inhibitor is present in an administration amount of about 0.1-500 mg/kg, cyclodextrin is present in an administration amount of about 1000-40,000 mg/kg, and the PEG is present in an amount of about 30-60% composition by weight.

11. The method of claim 7 , wherein the HDAC inhibitor is vorinostat at an administration amount of about 50 mg/kg, the cyclodextrin is HPBCD at an administration amount of at about 2000 mg/kg, and PEG is about 40-50% composition by weight.

12. The method of any one of claim 7 , wherein the chronic pain comprises one or more of, chronic nociceptive pain, chronic neuropathic pain, chronic inflammatory pain, fibromyalgia, breakthrough pain, persistent pain, hyperalgesia, allodynia, central sensitization, peripheral sensitization, disinhibition and augmented facilitation, or cancer pain.

Assignees

• Univ Northwestern
• The Univ Of Notre Dame Du Lac

Inventors

• Apkarian A Vania
• Haldar Kasturi
• Alam Suhail
• Centeno Maria Virginia

Classifications

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K31/167 Primary

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title