Topical therapy for the treatment of migranes, 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.

Description

BACKGROUND OF THE INVENTION [0001] The present invention is directed to methods and formulations for treating migraines, muscle sprains, muscle spasms, spasticity, tension headache, tension-related migraines and related conditions associated with muscle tension and pain. [0002] Migraine headaches are a debilitating condition in which some 53 million persons per year suffer acute pain. Frequently, migraine is accompanied by sickness and vomiting and a sensitivity to light and noise. [0003] Several theories on the pathogenesis of migraine have been hypothesized and include: i) the vascular theory (i.e., migraine is a vasospastic disorder that is initiated by vasoconstriction in the cranial vasculature); ii) the cortical spreading depression theory (i.e., CSD begins with a brief wave of excitation, followed by a prolonged period of neuronal depression, which is associated with disturbances in nerve cell metabolism and regional reductions in blood flow); iii) the neurovascular hypothesi...

AI Technical Summary

Benefits of technology

[0025] It is an object of certain embodiments of the present invention to provide a more rapid therapeutic effect than previous routes of administration of a therapeutically effective amount of an active agent(s) for the treatment of migraines and / or cluster headaches, muscle sprains, muscle spasms, spasticity, tension headaches, tension-related migraines and related conditions associated with muscle tension and pain.

[0026] It is another object of certain embodiments of the present invention to provide a topical formulation for the treatment of migraines and / or cluster headaches, muscle sprains, muscle spasms, spasticity, tension headaches, tension-related migraines and related conditions associated with muscle tension and pain in humans with an active agent(s) that provides a more rapid therapeutic effect than previous routes of administration of the active agent(s). In certain other embodiments, the active agent(s) provide a localized effect and / or reduced side effects.

[0030] In certain embodiments, the present invention is further directed to a method for treating a migraines and / or cluster headache comprising applying a unit dose of an active agent(s) effective for treating a migraine or cluster headache incorporated into a pharmaceutically acceptable excipient for topical administration onto the skin of a human patient; the unit dose providing the active agent(s) in an effective concentration in the excipient such that the unit dose when applied to a headache region of a human patient provides relief from a migraine or cluster headache within about 2 hours after topical administration to the human patient.

[0042] In certain other embodiments, the formulations described herein are fast acting. For example, the symptoms associated with migraine and / or cluster headache, muscle sprain, muscle spasm, spasticity, tension related headache, tension related migraine and related conditions associated with muscle tension and pain are relieved within about 2 hours, preferably within about 5 minutes to about 2 hours, within about 5 minutes to about 1 hour and most preferably within about 5 minutes to about 30 minutes after application of the formulation. In certain preferred embodiments, the formulations of the present invention provide relief from migraine and / or cluster headache, muscle sprain, muscle spasm, spasticity, tension related headache, tension related migraine and related conditions associated with muscle tension and pain within from less than 1 minute to about 2 hours, from about 1 minute to about 2 hours, and most preferably from about 1 minute to about 15 minutes.

[0045] In certain embodiments, the present invention provides a topical formulation for treating a migraine or cluster headache comprising a serotonin agonist and one or more additional active agent(s) incorporated into a pharmaceutically acceptable vehicle for topical administration onto the skin of a human patient; the formulation provides the serotonin agonist and the additional active agent(s) in a form which is immediately absorbable when the formulation is applied onto human skin; the serotonin agonist comprising from about 0.5 to about 200 mg of sumatriptan, by weight based on the succinate salt; and the formulation provides relief from a migraine or cluster headache within about 2 hours after topical administration to a human patient.

[0046] In certain embodiments, the present invention provides a topical formulation for treating muscle sprains, muscle spasms, spasticity, tension headaches, tension related migraines and related conditions associated with muscle tension and pain comprising a therapeutically effective amount of a serotonin agonist together with a therapeutically effective amount of a muscle relaxant (e.g., tizanidine) in a pharmaceutically acceptable vehicle for topical administration such that the formulation provides pain relief in at least 50 percent of a population of patients experiencing muscle sprains, muscle spasms, spasticity, tension headaches, tension related migraines and related conditions associated with muscle tension and pain, in a time period within about 2 hours after application of the unit dose to the affected area.

Problems solved by technology

Frequently, migraine is accompanied by sickness and vomiting and a sensitivity to light and noise.

Muscle sprains, muscle spasms, spasticity, tension headaches and tension-related migraines are also common debilitating conditions that are associated with acute pain, chronic pain and involuntary movement that can be so severe that the condition(s) frequently disrupt an individual's daily life.

The result is chronic, severe spasm of the muscles of the extremities hindering function and causing pain.

All of these compounds, however, have some adverse effects which require supervised administration at efficacious doses.

Typically, transdermal systems are not used in acute situations because they do not provide an immediate effect, but rather provide prophylaxis or prolonged effect.

The drawback of the oral or parenteral administration is that there are frequent systemic side effects such as fatigue, lethargy, weakness and mental clouding, particularly as higher doses are reached.

Benzodiazepines, e.g., diazepam, have additional drawbacks such as tolerance, psychological dependency and withdrawal effects, e.g., seizures.