Topical Therapy for the Treatment of Migraines, Muscle Sprains, Muscle Spasms, Spasticity and Related Conditions

Abstract

The invention is directed to topical formulations and methods of treating a migraines and/or cluster headaches, muscle sprains, muscle spasms, spasticity, tension headaches, tension related migraines and related conditions associated with muscle tension and pain with a therapeutically effective amount of an ergot alkaloid, skeletal muscle relaxant, serotonin agonist, combinations thereof, pharmaceutically acceptable salt thereof, prodrugs thereof or derivative thereof.

1 - 73 . (canceled) 
     
     
         74 . A method of treating migraines, cluster headaches, muscle sprains, muscle spasms, spasticity, tension headaches and tension related migraines with a topical formulation comprising applying a therapeutically effective amount of an active agent(s) comprising a skeletal muscle relaxant or a pharmaceutically acceptable salt thereof onto the skin of a human patient experiencing an acute condition selected from the group consisting of migraine, cluster headache, muscle sprain, muscle spasm, spasticity, tension headache and tension related migraine at the posterior cervical area in close proximity to the brain stem, such that the unit dose provides a therapeutic effect within about 15 to about 30 minutes after topical administration to the human patient. 
     
     
         75 . The method of  claim 74 , further comprising applying a therapeutically effective amount of a serotonin agonist onto the skin of a human patient experiencing an acute condition selected from the group consisting of migraine, cluster headache, muscle sprain, muscle spasm, spasticity, tension headache and tension related migraine at the posterior cervical area in close proximity to the brain stem. 
     
     
         76 . The method of  claim 74 , further comprising applying a therapeutically effective amount of an ergot alkaloid onto the skin of a human patient experiencing an acute condition selected from the group consisting of migraine, cluster headache, muscle sprain, muscle spasm, spasticity, tension headache and tension related migraine at the posterior cervical area in close proximity to the brain stem. 
     
     
         77 . The formulation of  claim 74 , wherein the skeletal muscle relaxant is selected from the group consisting of afloqulone, baclofen, botulin toxins, carisoprodol, chlormezanone, chlorphenesin carbamate, chlorzoxasozone, cyclobenzaprine, clonazepam, dantrolene, diazepam, eperisone, idrocilamide, inaperisone, mephenesin, mephenoxalone, methocarbamol, metaxalone, mivacurium chloride, orphenadrine, phenprobamate, pridinol mesylate, quinine, tetrazepam, thiocolchicoside, tizanidine, tolperisone, pharmaceutically acceptable salts thereof, active metabolites thereof, prodrugs thereof and mixtures thereof. 
     
     
         78 . The method of  claim 75 , wherein the serotonin agonist is selected from the group consisting of sumatriptan, naratriptan, eletriptan, rizatriptan, zolmitriptan, almotriptan, frovatriptan, pharmaceutically acceptable salts thereof, and mixtures thereof. 
     
     
         79 . The method of  claim 76 , wherein the ergot alkaloid is selected from the group consisting of bromocriptine, ergocristine, ergocristinine, ergotamine, ergotaminine, ergocryptine, ergocryptinine, ergocornine, ergocorninine, ergosine, ergosinine, ergonovine, ergometrinine, dihydroergotamine, lisuride, d-lysergic acid, d-isolysergic acid, lysergol, lergotrile, metergoline, methysergide, methylergonovine, pharmaceutically acceptable salts thereof, and mixtures thereof. 
     
     
         80 . The method of  claim 74 , further comprising applying a unit dose of a therapeutically effective amount of a serotonin agonist and an effective amount of an ergot alkaloid onto the skin of a human patient experiencing an acute condition selected from the group consisting of migraine, cluster headache, muscle sprain, muscle spasm, spasticity, tension headache and tension related migraine at the posterior cervical area in close proximity to the brain stem. 
     
     
         81 . The method of  claim 80 , wherein the skeletal muscle relaxant is selected from the group consisting of afloqulone, baclofen, botulin toxins, carisoprodol, chlormezanone, chlorphenesin carbamate, chlorzoxasozone, cyclobenzaprine, clonazepam, dantrolene, diazepam, eperisone, idrocilamide, inaperisone, mephenesin, mephenoxalone, methocarbamol, metaxalone, mivacurium chloride, orphenadrine, phenprobamate, pridinol mesylate, quinine, tetrazepam, thiocolchicoside, tizanidine, tolperisone, pharmaceutically acceptable salts thereof, active metabolites thereof, prodrugs thereof and mixtures thereof. 
     
     
         82 . The method of  claim 81 , wherein the serotonin agonist is selected from the group consisting of sumatriptan, naratriptan, eletriptan, rizatriptan, zolmitriptan, almotriptan, frovatriptan, pharmaceutically acceptable salts thereof, and mixtures thereof. 
     
     
         83 . The method of  claim 82 , wherein the ergot alkaloid is selected from the group consisting of bromocriptine, ergocristine, ergocristinine, ergotamine, ergotaminine, ergocryptine, ergocryptinine, ergocornine, ergocorninine, ergosine, ergosinine, ergonovine, ergometrinine, dihydroergotamine, lisuride, d-lysergic acid, d-isolysergic acid, lysergol, lergotrile, metergoline, methysergide, methylergonovine, pharmaceutically acceptable salts thereof, and mixtures thereof. 
     
     
         84 . The method of  claim 74 , further comprising incorporating the active agent into an aqueous based formulation. 
     
     
         85 . The method of  claim 74 , further comprising preparing the topical formulation in a form selected from the group consisting of a liquid, a semisolid, a solid and mixtures thereof. 
     
     
         86 . The method of  claim 74 , further comprising incorporating a therapeutic amount of active agent(s) into the unit dose such that the active agent(s) would provide a subtherapeutic plasma level if orally administered, but are therapeutically effective when administered topically at the posterior cervical area. 
     
     
         87 . The method of  claim 74 , wherein skeletal muscle relaxant comprises from about 0.2 mg to about 8 mg of tizanidine hydrochloride. 
     
     
         88 . The method of  claim 74 , wherein the skeletal muscle relaxant comprises cyclobenzaprine. 
     
     
         89 . The method of  claim 75 , wherein the serotonin agonist comprises sumatriptan. 
     
     
         90 . The method of  claim 75 , wherein the serotonin agonist comprises from about 0.5 mg to about 200 mg sumatriptan. 
     
     
         91 . The method of  claim 76 , wherein the therapeutically effective amount of ergot alkaloid ranges from about 0.1 mg to about 10 mg. 
     
     
         92 . A method of treating migraines, cluster headaches, muscle sprains, muscle spasms, spasticity, tension headaches and tension related migraines with a topical formulation comprising applying a therapeutically effective amount of a skeletal muscle relaxant or a pharmaceutically acceptable salt thereof incorporated into an immediate release pharmaceutically acceptable carrier onto the skin of a human patient at the posterior cervical area in close proximity to the brain stem, wherein the human patient is experiencing an acute condition selected from the group consisting of migraine, cluster headache, muscle sprain, muscle spasm, spasticity, tension headache and tension related migraine, such that the unit dose provides a therapeutic effect within about 30 minutes after the topical administration. 
     
     
         93 . The method of  claim 92 , further comprising applying an additional therapeutically effective amount of the skeletal muscle relaxant onto the skin of the human patient at the posterior cervical area from about 15 minutes to about 3 hours after the first application of the unit dose. 
     
     
         94 . The method of  claim 92 , further comprising applying a therapeutically amount of a serotonin agonist onto the skin of a human patient at the posterior cervical area in close proximity to the brain stem. 
     
     
         95 . The method of  claim 92 , further comprising applying a therapeutically effective amount of an ergot alkaloid onto the skin of a human patient at the posterior cervical area in close proximity to the brain stem. 
     
     
         96 . The method of  claim 92 , wherein the skeletal muscle relaxant is selected from the group consisting of afloqulone, baclofen, botulin toxins, carisoprodol, chlormezanone, chlorphenesin carbamate, chlorzoxasozone, cyclobenzaprine, clonazepam, dantrolene, diazepam, eperisone, idrocilamide, inaperisone, mephenesin, mephenoxalone, methocarbamol, metaxalone, mivacurium chloride, orphenadrine, phenprobamate, pridinol mesylate, quinine, tetrazepam, thiocolchicoside, tizanidine, tolperisone, pharmaceutically acceptable salts thereof, active metabolites thereof, prodrugs thereof and mixtures thereof. 
     
     
         97 . The method of  claim 94 , wherein the serotonin agonist is selected from the group consisting of sumatriptan, naratriptan, eletriptan, rizatriptan, zolmitriptan, almotriptan, frovatriptan, pharmaceutically acceptable salts thereof, and mixtures thereof. 
     
     
         98 . The method of  claim 95 , wherein the ergot alkaloid is selected from the group consisting of bromocriptine, ergocristine, ergocristinine, ergotamine, ergotaminine, ergocryptine, ergocryptinine, ergocornine, ergocorninine, ergosine, ergosinine, ergonovine, ergometrinine, dihydroergotamine, lisuride, d-lysergic acid, d-isolysergic acid, lysergol, lergotrile, metergoline, methysergide, methylergonovine, pharmaceutically acceptable salts thereof, and mixtures thereof.