Triple combination formulation for treatment of chronic pain

Abstract

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

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. 
     
     
         2 . The method of  claim 1 , wherein the HDAC inhibitor is vorinostat. 
     
     
         3 . The method of  claim 1 , wherein the cyclodextrin is 2-hydroxypropyl-b-cyclodextrin (HPBCD). 
     
     
         4 . The method of  claim 1 , wherein the polyethylene glycol (PEG) or propylene glycol is polyethylene glycol. 
     
     
         5 . 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. 
     
     
         6 . 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. 
     
     
         7 . 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. 
     
     
         8 . 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. 
     
     
         9 . 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. 
     
     
         10 . The method of  claim 9 , wherein the HDAC inhibitor is vorinostat. 
     
     
         11 . The method of  claim 9 , wherein the cyclodextrin is 2-hydroxypropyl-b-cyclodextrin (HPBCD). 
     
     
         12 . The method of  claim 9 , wherein the polyethylene glycol (PEG) or propylene glycol is polyethylene glycol. 
     
     
         13 . The method of  claim 9 , wherein the composition comprises a molar ratio of HDAC inhibitor:cyclodextrin:PEG of about 1-100:1-1000:1-1000. 
     
     
         14 . The method of  claim 9 , 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. 
     
     
         15 . The method of  claim 9 , 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. 
     
     
         16 . The method of any one of  claim 9 , 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. 
     
     
         17 . Use of a composition comprising (i) a histone deacetylase (HDAC) inhibitor, (ii) a cyclodextrin or salt thereof, and (iii) polyethylene glycol (PEG) or propylene glycol for manufacture of a medicament for the treatment of chronic pain or inhibition of symptoms of chronic pain. 
     
     
         18 . The use according to  claim 17 , wherein the medicament is prepared to be administered orally, sublingually, vial inhalation, transdermal, subcutaneously, intravenously, intraperitoneally, intra-arterially, intra-articulary, peri-articularly, locally, or intramuscularly. 
     
     
         19 . The use according to  claim 18 , wherein the medicament is prepared to be orally or intravenously administered. 
     
     
         20 . The use according to  claim 17 , wherein the HDAC inhibitor is vorinostat, the cyclodextrin is 2-hydroxypropyl-b-cyclodextrin (HPBCD) and polyethylene glycol (PEG) or propylene glycol is polyethylene glycol. 
     
     
         21 . The use according to  claim 17 , wherein the composition comprises a molar ratio of HDAC inhibitor:cyclodextrin:PEG of about 1-100:1-1000:1-1000. 
     
     
         22 . The use according to  claim 17 , wherein the HDAC inhibitor is present 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. 
     
     
         23 . The use according to  claim 17 , 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. 
     
     
         24 . The use according to  claim 17 , 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.