Topical therapy for the treatment of migraines, muscle sprains, muscle spasms, spasticity and related conditions

• US 8,883,830 B2
• Filed: 01/13/2012
• Issued: 11/11/2014
• Est. Priority Date: 06/20/2003
• Status: Active Grant

• Current Assignee: Psycheceutical, Inc.
• Original Assignee: Afgin Pharma LLC
• Inventors: Aung-Din, Ronald
• Primary Examiner(s): MCMILLIAN, KARA RENITA
• Application Number:
  US13/349,849
• Publication Number:
  US 20120114741A1
• Time in Patent Office: 1,033 Days
• Field of Search: 514/362, 514/415, 514/288, 514/250
• US Class Current: 514/362
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61K 31/433 Thidiazoles
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/06 Antimigraine agents

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.

Claims

1. A method of treating migraines and cluster headaches with a topical formulation comprising applying a unit dose of a therapeutically effective amount of the active agent tizanidine or a pharmaceutically acceptable salt thereof incorporated into an immediate release pharmaceutically acceptable topical carrier onto the skin of a human patient experiencing an acute condition selected from the group consisting of migraine and cluster headache, 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.

2. The method of claim 1, wherein the formulation further comprises a therapeutically effective amount of a serotonin agonist.

3. The method of claim 1, wherein the topical carrier is an aqueous based carrier.

4. The method of claim 1, wherein the topical formulation in a form selected from the group consisting of a liquid, a semisolid, a solid and mixtures thereof.

5. The method of claim 1, further comprising incorporating a therapeutic amount of the active agent into the unit dose such that the active agent would provide a subtherapeutic plasma level if orally administered, but is therapeutically effective when administered topically at the posterior cervical area.

6. The method of claim 1, wherein the unit dose further comprises a therapeutically effective amount of an ergot alkaloid 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.

7. The method of claim 6, wherein the ergot alkaloid is selected from the group consisting of dihydroergotamine base, dihydroergotamine mesylate, and mixtures thereof.

8. The method of claim 6, wherein the therapeutically effective amount of ergot alkaloid ranges from about 0.1 mg to about 10 mg, preferably from about 0.5 mg to about 6 mg.

9. The method of claim 1, wherein the unit dose comprises from about 0.2 mg to about 8 mg of tizanidine hydrochloride.

10. The method of claim 2, 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.

11. The method of claim 10, wherein the serotonin agonist is sumatriptan.

12. The method of claim 11, wherein the unit dose comprises from about 0.5 mg to about 200 mg sumatriptan.

13. The method of claim 11, wherein the unit dose comprises from about 5 mg to about 50 mg sumatriptan.

14. The method of claim 1, further comprising incorporating one or more ingredients into the topical formulation selected from the group consisting of ethoxydiglycol, water, glycerine, C12-15alkyl benzoate, glyceryl stearate, dimethicone, cetearyl alcohol, cetearyl glucoside, polyacrylamide, cetyl alcohol, magnesium aluminum silicate, xanthan gum, aloe vera (aloe barbadensis), tocopheryl acetate (vitamin E acetate), prunus amygadalus amara (bitter almond) kernel oil, vitis vinifera (grape) seed extract, triticum vulgare (wheat) germ oil, retinyl palmitate (vitamin A palmitate), ascorbyl palmitate (vitamin C palmitate), pro-lipo multi-emulsion liposomic system, tetrasodium EDTA, phenoxyethanol, and sodium hydroxymethylglycinate.

15. The method of claim 1, wherein the unit dose comprises from about 0.2 mg to about 4 mg of tizanidine hydrochloride.

16. A method of treating migraines and cluster headaches with a topical formulation comprising applying a unit dose of from about 0.2 mg to about 8 mg of tizanidine hydrochloride and from about 0.5 mg to about 200 mg sumatriptan succinate, incorporated into a pharmaceutically acceptable carrier, onto the skin of a human patient experiencing an acute condition selected from the group consisting of migraine and cluster headache, at the posterior cervical area in close proximity to the brain stem of the human patient, such that the unit dose provides a therapeutic effect within about 15 to about 30 minutes after topical administration to the human patient.

17. The method of claim 16, wherein the unit dose comprises from about 0.4 mg to 4 mg of tizanidine hydrochloride and from about 5 mg to 50 mg sumatriptan succinate.

18. The method of claim 16, further comprising applying an additional unit dose 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.

19. The method of claim 16, wherein the topical formulation further comprises from about 0.1 mg to about 10 mg of an ergot alkaloid.

20. The method of claim 16, wherein the pharmaceutical acceptable carrier is aqueous-based.