METHODS AND COMPOSITIONS FOR THE TREATMENT OF MIGRAINE HEADACHES

• US 20120329764A1
• Filed: 01/10/2011
• Published: 12/27/2012
• Est. Priority Date: 01/08/2010
• Status: Abandoned Application

• Current Assignee: Beth Israel Deaconess Medical Center, Inc. (Beth Israel Lahey Health, Inc.)
• Original Assignee: Beth Israel Deaconess Medical Center, Inc. (Beth Israel Lahey Health, Inc.)
• Inventors: Burstein, Rami, Buettner, Catherine
• Application Number:
  US13/520,054
• Publication Number:
  US 20120329764A1
• Time in Patent Office: Days
• US Class Current: 514/167
• 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 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/592 9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention is related to compositions and methods for treating or reducing the likelihood of a migraine, reducing the severity of migraine, reducing the frequency of migraines, reducing the duration of migraine, and ameliorating the symptoms of a migraine. The methods and compositions of the present invention may also be used to treat or prevent condition characterized by increased cardiovascular risk or endothelial dysfunction and musculoskeletal symptoms.

Claims

1. A method of treating or reducing the likelihood of a migraine, ameliorating the symptoms of a migraine, reducing the frequency or duration of migraines, or treating a condition characterized by increased cardiovascular risk or endothelial dysfunction and musculoskeletal symptoms in a subject in need thereof, said method comprising administering to said subject (i) a statin or an analog thereof and (ii) vitamin D or an analog thereof, wherein said statin or analog thereof and said vitamin D or analog thereof are administered in amounts and for a duration that together are sufficient to treat or reduce the likelihood of a migraine in said subject, to ameliorate the symptoms of a migraine in said subject, to reduce the frequency or duration of migraines in said subject, or to treat said condition.

5. The method of claim 1, wherein said condition is statin-associated musculoskeletal pain or weakness, arthritis, neuromuscular disease, a condition associated with stroke rehabilitation, or a condition associated with myocardial infarction rehabilitation.

6. The method of claim 1, wherein said statin is atorvastatin;

cerivastatin;

fluvastatin;

lovastatin;

rosuvastatin;

acitemate;

amlodipine/atorvastatin;

BAY102987;

BAY X 2678;

BB476;

bervastatin;

BMY21950;

BMY22089;

colestolone;

CP83101;

dalvastatin;

DMP565;

ezetimibe/simvastatin;

glenvastatin;

L659699;

L669262;

mevastatin;

nicotinic acid/lovastatin;

nicotinic acid/simvastatin;

P882222;

P882284;

PD134965;

PD135022;

pitavastatin;

rosuvastatin;

RP61969;

S2468;

SC37111;

SC45355;

simvastatin;

SQ33600;

SR12813;

SR45023A;

U20685; and

U88156.

7. The method of claim 6, wherein said statin is simvastatin.

8. The method of claim 1, wherein said vitamin D or vitamin D analog is doxercalciferol, calcitriol, α

-calcidol, seocalcitol, calcipotriol, maxacalcitol, falecalcitriol, paricalcitol, alfacalcidol, calcifediol, cholecalciferol, dihydrotachysterol, ergosterol, ergocalciferol, 1α

,2-dihydroxyvitamin D₄, 1α

,24-dihydroxyvitamin D₂, 1α

,25-dihydroxyvitamin D₂, 1α

,25-dihydroxyvitamin D₄, or 1α

,24,25-dihydroxyvitamin D₂.

9. The method of claim 8, wherein said vitamin D or vitamin D analog is cholecalciferol or ergocalciferol.

10. The method of claim 9, wherein said statin is simvastatin and said vitamin D or vitamin D analog is cholecalciferol.

11. The method of claim 9, wherein said statin is simvastatin and said vitamin D or vitamin D analog is ergocalciferol.

13. The method of claim 1, wherein said statin or analog thereof and said vitamin D or analog thereof are administered simultaneously or sequentially.

14. The method of claim 1, wherein said method further comprises administering an additional therapeutic agent to said subject.

15. The method of claim 14, wherein said additional therapeutic agent is an analgesic, a β

-blocker, a calcium channel blocker, an antiemetic, a serotonin receptor agonist, a barbiturate, an antidepressant, an ergot alkaloid, a steroid, an anxiolytic, an amphetamine, a NOS inhibitor, a narcotic, or an anticonvulsant.

16. The method of claim 15, wherein said analgesic is a non-steroidal anti-inflammatory agent, said antidepressant is a tricyclic antidepressant, or said anticonvulsant is valproic acid.

19. The method of claim 1, wherein said subject is a human subject.

2-4. -4. (canceled)

12. (canceled)

17-18. -18. (canceled)

20. A pharmaceutical composition comprising (i) a statin or an analog thereof, (ii) vitamin D or an analog thereof, and (iii) a pharmaceutically acceptable carrier, wherein said statin or analog thereof and said vitamin D or analog thereof are present in an amount that, when administered to a subject, are sufficient to treat or reduce the likelihood of a migraine in said subject, to ameliorate the symptoms of a migraine in said subject, to reduce the frequency or duration of migraines in said subject, or to treat a condition characterized by increased cardiovascular risk or endothelial dysfunction and musculoskeletal symptoms in said subject.

24. The pharmaceutical composition of claim 20, wherein said condition is statin-associated musculoskeletal pain or weakness, arthritis, neuromuscular disease, stroke rehabilitation, or myocardial infarction rehabilitation.

25. The pharmaceutical composition of claim 20, wherein said statin or analogs thereof and said vitamin D or analogs thereof are formulated in a single composition.

26. The pharmaceutical composition of claim 20, wherein said statin or analogs thereof and said vitamin D or analogs thereof are formulated for oral administration, systemic administration, inhalation, or topical application.

30. The pharmaceutical composition of claim 20, wherein said statin is atorvastatin;

cerivastatin;

fluvastatin;

lovastatin;

rosuvastatin;

acitemate;

amlodipine/atorvastatin;

BAY102987;

BAY X 2678;

BB476;

bervastatin;

BMY21950;

BMY22089;

colestolone;

CP83101;

dalvastatin;

DMP565;

ezetimibe/simvastatin;

glenvastatin;

L659699;

L669262;

mevastatin;

nicotinic acid/lovastatin;

nicotinic acid/simvastatin;

P882222;

P882284;

PD134965;

PD135022;

pitavastatin;

rosuvastatin;

RP61969;

S2468;

SC37111;

SC45355;

simvastatin;

SQ33600;

SR12813;

SR45023A;

U20685; and

U88156.

31. The pharmaceutical composition of claim 30, wherein said statin is simvastatin.

32. The pharmaceutical composition of claim 20, wherein said vitamin D or vitamin D analog is doxercalciferol, calcitriol, α

-calcidol, seocalcitol, calcipotriol, maxacalcitol, falecalcitriol, paricalcitol, alfacalcidol, calcifediol, cholecalciferol, dihydrotachysterol, ergosterol, ergocalciferol, 1α

,2-dihydroxyvitamin D₄, 1α

,24-dihydroxyvitamin D₂, 1α

,25-dihydroxyvitamin D₂, 1α

,25-dihydroxyvitamin D₄, or 1α

,24,25-dihydroxyvitamin D₂.

33. The pharmaceutical composition of claim 32, wherein said vitamin D or vitamin D analog is cholecalciferol or ergocalciferol.

34. The pharmaceutical composition of claim 33, wherein said statin is simvastatin and said vitamin D or vitamin D analog is cholecalciferol.

35. The pharmaceutical composition of claim 33, wherein said statin is simvastatin and said vitamin D or vitamin D analog is ergocalciferol.

37. The pharmaceutical composition of claim 20, wherein said composition further comprises an additional therapeutic agent.

38. The pharmaceutical composition of claim 37, wherein said additional therapeutic agent is an analgesic, a β

-blocker, a calcium channel blocker, an antiemetic, a serotonin receptor agonist, a barbiturate, an antidepressant, an ergot alkaloid, a steroid, an anxiolytic, an amphetamine, a NOS inhibitor, a narcotic, or an anticonvulsant.

39. The pharmaceutical composition of claim 38, wherein said analgesic is a non-steroidal anti-inflammatory agent, said antidepressant is a tricyclic antidepressant, or said anticonvulsant is valproic acid.

21-23. -23. (canceled)

27-29. -29. (canceled)

36. (canceled)

40-41. -41. (canceled)