Pharmaceutical compositions of spiro-oxindole compound for topical administration and their use as therapeutic agents

Abstract

This invention is directed to pharmaceutical compositions for topical administration to a mammal, wherein the pharmaceutical compositions comprise a spiro-oxindole compound, as an enantiomer, a racemate or a non-racemic mixture, or a pharmaceutically acceptable salt thereof. These pharmaceutical compositions are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions.

1 .- 20 . (canceled) 
     
     
         21 . A method of treating, preventing or ameliorating a sodium channel-mediated disease or a condition in a mammal, wherein the method comprises topically administering to the mammal in need thereof a therapeutically effective amount of a pharmaceutical composition comprising two or more pharmaceutically acceptable excipients and a therapeutically effective amount of a spiro-oxindole compound having the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein each pharmaceutically acceptable excipient is present in a concentration of from about 0.01% w/w to about 99% w/w, wherein the pharmaceutically acceptable excipients are selected from one or more solvents, one or more penetration enhancing agents, one or more stiffening agents, one or more ointment bases and, optionally, one or more antioxidants, and wherein a solvent is selected from PEG 400 or PEG 3350, a penetration enhancing agent is selected from diethylene glycol monoethyl ether, oleyl alcohol, or isopropyl myristate, a stiffening agent is stearyl alcohol, an ointment base is selected from PEG 400 or PEG 3350, and the antioxidant, if present, is butylated hydroxytoluene (BHT), and wherein said disease or condition is selected from the group consisting of neuropathic pain, inflammatory pain, visceral pain, post-herpetic neuralgia, cancer pain, chemotherapy pain, trauma pain, surgical pain, post-operative pain, pruritis, trigeminal neuralgia, familial erythromelalgia, primary erythromelalgia, familial rectal pain, childbirth pain, labor pain, neurogenic bladder, ulcerative colitis, chronic pain, persistent pain, peripherally mediated pain, centrally mediated pain, chronic headache, migraine headache, sinus headache, tension headache, phantom limb pain, peripheral nerve injury, and combinations thereof. 
     
     
         22 . The method of  claim 21 , wherein said disease or condition is selected from the group consisting of neuropathic pain, inflammatory pain, post-herpetic neuralgia, trigeminal neuralgia, familial erythromelalgia, primary erythromelalgia and combinations thereof. 
     
     
         23 . The method of  claim 21 , wherein the mammal is a human. 
     
     
         24 . A method of treating pain through inhibition of ion flux through a voltage-dependent sodium channel in a mammal, wherein the method comprises topically administering to the mammal in need thereof a therapeutically effective amount of a pharmaceutical composition comprising two or more pharmaceutically acceptable excipients and a therapeutically effective amount of a spiro-oxindole compound having the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein each pharmaceutically acceptable excipient is present in a concentration of from about 0.01% w/w to about 99% w/w, wherein the pharmaceutically acceptable excipients are selected from one or more solvents, one or more penetration enhancing agents, one or more stiffening agents, one or more ointment bases and, optionally, one or more antioxidants, and wherein a solvent is selected from PEG 400 or PEG 3350, a penetration enhancing agent is selected from diethylene glycol monoethyl ether, oleyl alcohol, or isopropyl myristate, a stiffening agent is stearyl alcohol, an ointment base is selected from PEG 400 or PEG 3350, and the antioxidant, if present, is butylated hydroxytoluene (BHT). 
     
     
         25 . The method of  claim 24 , wherein the mammal is a human.