AU2012212380B2 - Composition and method for the treatment of headache - Google Patents

Composition and method for the treatment of headache Download PDF

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Publication number
AU2012212380B2
AU2012212380B2 AU2012212380A AU2012212380A AU2012212380B2 AU 2012212380 B2 AU2012212380 B2 AU 2012212380B2 AU 2012212380 A AU2012212380 A AU 2012212380A AU 2012212380 A AU2012212380 A AU 2012212380A AU 2012212380 B2 AU2012212380 B2 AU 2012212380B2
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Australia
Prior art keywords
headaches
vitamin
composition
severity
reduction
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AU2012212380A
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AU2012212380A1 (en
Inventor
Raymond SCHWARTZ
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HEALTH-EASE Pty Ltd
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HEALTH EASE Pty Ltd
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Priority claimed from AU2011900328A external-priority patent/AU2011900328A0/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A composition for preventing or reducing the frequency and severity of headaches in a subject predisposed to said headaches, the composition comprising: one or more B group vitamins or feverfew extract or combinations of the above, with or without magnesium.

Description

COMPOSITION COMPRISING B GROUP VITAMINS OR FEVERFEW AND TREATMENT OF HEADACHES WITH SUCH COMPOSITIONS
Field of the invention: [0001] The invention relates to compositions and methods for the treatment of headache, in particular to headaches on the spectrum of tension headache and migraine.
Background.
[0002] Almost all people suffer headaches from time to time. However, a small but significant portion of the population suffer a chronically high incidence of headaches, or are predisposed to headache. These headaches are generally on the spectrum of tension headache and migraine. Γ0003] Australian therapeutic guidelines recommend regular prophylactic treatment for patients with a history of more than two or three migraine attacks per month.
[0004] The compounds used to treat migraine fall within a wide range of modes of action and therapeutic class, and can include beta blockers, 5HT antagonists, antiepileptics, antihypotensives, anticonvulsants and antihistamines. However, most professionals are somewhat guarded as to the efficacy of these compounds, especially as a number of patients become tolerant of the effects of a particular dmg in the long term. The long term use of these drugs as necessitated by the chronic nature of the conditions is also of particular concern as the cumulative nature of any side effects can have serious ramifications. For instance, sodium valproate and pizotifen cause weight gain. Topiramate can affect the patient’s mental state and cause weight loss. Metoprolol can affect blood pressure and pulse rate. Clonidine can cause drowsiness [0005] Accordingly, from time to time it is necessary to review and re-assess the medication provided to a particular patient. As well as induced tolerance and the manifestation of severe side effects, keeping a patient on a particular· medication for an extended period is undesirable as it increases the likelihood of a rebound exacerbation of migraine should that particular medication need to be withdrawn.
[0006] Thus, it is desirable to rotate a patient’s medication from time to time. Another benefit in rotating medications is the well established “placebo effect” whereby somewhere between 20 and 40% of patients observe an improvement in the frequency and severity of headaches when a new medication is prescribed, even when that new medication is in fact a placebo. There is a strong psychosomatic factor present but nevertheless the benefits of this placebo effect to the patient are very real.
[0007] Accordingly, there is a need for new therapeutic agents to expand the suite of medications available for the prophylaxis and/or moderation of migraines and other headaches on the spectrum of tension headache and migraine. Ideally, the new therapeutic agents are as free from side effects as possible, and are as efficacious as possible.
[0008] It is an object of the present invention to overcome or ameliorate the above problems, or at least provide a commercial alternative.
[0008a] Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.
[0008b] Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.
Summary of the Invention [0008c] According to a first aspect the present invention provides a dosage form for reducing the frequency and severity of headaches comprising: feverfew extract containing a minimum of 400mcg parthenolides; 10-100 mg magnesium orotate; 10-200 mg riboflavin (vitamin B2); 0.1-1.0 mg folic acid (vitamin B9); 10-500 mg pyridoxine HC1 (vitamin B6); and 0.1-1.0 mg cyanocobalamin (vitamin B12).
[0008d] According to a second aspect the present invention provides a dosage form according to the invention in the form of a capsule.
[0008e] According to a third aspect the present invention provides a method for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches comprising administering to a subject in need thereof a dosage form according to the invention.
[0008f] According to a fourth aspect the present invention provides use of a dosage form according to the invention for the manufacture of a medicament for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches.
[0009] Described herein is a composition for reducing the frequency and severity of headaches in a subject predisposed to said headaches, the composition comprising one or more B group vitamins.
[0010] Also described herein is a composition for reducing the frequency and severity of headaches comprising one or more B group vitamins and feverfew extract.
[0011] Further described herein is a composition for reducing the frequency and severity of headaches comprising one or more B group vitamins and magnesium.
[0012] In addition, herein described is a composition for reducing the frequency and severity of headaches comprising one or more B group vitamins, feverfew extract and magnesium.
[0013] Also described herein is a composition for reducing the frequency and severity of headaches comprising feverfew extract and magnesium.
[0014] Further described is a composition wherein the B group vitamins are selected from B2, B6, B9 or B12.
[0015] Described is also a composition for reducing the frequency and severity of headaches comprising two or more B group vitamins.
[0016] Additionally described is a composition comprising two or more B group vitamins selected from B2+B6, B2+B9, B2+B12, B6+B9, B6+B12 or B9+B12.
[0017] Further described is a composition comprising three or more B group vitamins.
[0018] Also described is a composition comprising three or more B group vitamins selected from B2+B6+B9, B2+B9+B12, B2+B6+B12 or B6+B9+B12.
[0019] Described herein too is a composition for the treatment of headache comprising four or more B group vitamins.
[0020] Also described is a composition for the treatment of headache comprising four or more B group vitamins which is B2+B6 +B9 +B12.
[0021] The compounds may be present in any ratio. Preferably, vitamin B2 is present in a greater amount, at least 4 times the amount of vitamin B6. B9 is preferably present in an amount of 1:2 to 2:1 relative to the amount of B12. Preferably B6 is present in an amount of 10 to 100 times the amount of B9 or B12. Preferably B2 is present in an amount 50 to200 times the amount of B9 or B12.
[0022] The ratio of B2:B6:B9:B12 is preferably 100:25:0.5:0.4, however it may be in the range 10-200:1-50:0.1-1.0:0.1-1.0.
[0023] Described herein is a composition for reducing the frequency and severity of headaches for the treatment of headache comprising: feverfew extract; magnesium; and one or more of Riboflavin (vitamin B2), folic acid (vitamin B9), pyridoxine HC1 (vitamin B6) and cyanocobalamin (vitamin B12) [0024] The feverfew extract is preferably standardised such that 200 mg provides 400mcg parthenolide.
[0025] The invention provides a composition wherein the magnesium is present as magnesium orotate.
[0026] Preferably, the material further contains a salt of orotic acid, such as magnesium orotate. If magnesium orotate is used, it is present in a ratio of about 1:2 with respect to B2 and 2:1 with respect to B6.
[0027] Described herein is a composition for the treatment of headache comprising: riboflavin (vitamin B2), folic acid (vitamin B9), pyridoxine HC1 (vitamin B6) and cyanocobalamin (vitamin B12) and feverfew.
[0028] Also described is a composition for reducing the frequency and severity of headaches comprising: feverfew extract; magnesium; riboflavin (vitamin B2); folic acid (vitamin B9); pyridoxine HC1 (vitamin B6); and cyanocobalamin (vitamin B12) [0029] The invention also provides a composition for reducing the frequency and severity of headaches comprising: 50-500 mg feverfew extract; 10-100 mg magnesium orotate; 10-200 mg riboflavin (vitamin B2); 0.1-1.0 mg folic acid (vitamin B9); 50-500 mg pyridoxine HC1 (vitamin B6); and 0.1-1.0 cyanocobalamin (vitamin B12) [0029a] The invention also provides a composition for reducing the frequency and severity of headaches comprising: feverfew extract containing a minimum of 400mcg parthenolides; about 55.4 mg magnesium orotate; about 100 mg riboflavin (vitamin B2); about 0.5 mg folic acid (vitamin B9); about 25 mg pyridoxine HC1 (vitamin B6); and about 0.4 mg cyanocobalamin (vitamin B12).
[0030] Described herein is a method for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches comprising administering to a subject in need a composition comprising one or more B group vitamins and feverfew extract.
[0031] Also described is a method for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches comprising administering to a subject in need a composition comprising one or more B group vitamins and magnesium.
[0032] Further described is a method for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches comprising administering to a subject in need a composition comprising one or more B group vitamins, feverfew extract and magnesium.
[0033] Described in additon is a method for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches comprising administering to a subject in need a composition comprising feverfew extract and magnesium.
[0034] Described herein is the use of a composition comprising one or more B group vitamins and feverfew extract for the manufacture of a medicament for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches.
[0035] Also described is the use of a composition comprising one or more B group vitamins and magnesium for the manufacture of a medicament for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches.
[0036] Further described is the use of a composition comprising one or more B group vitamins, feverfew extract and magnesium for the manufacture of a medicament for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches.
[0037] Described in addition is the use of a composition comprising, feverfew extract and magnesium for the manufacture of a medicament for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches.
[0038] In the methods of the present invention, the daily doses of the ingredients can be varied independently in accordance with the preferred values:
Feverfew 100-900 mg, preferably around 200mg;
Magnesium in an amount equivalent to 10-900 mg of magnesium orotate, preferably in an amount equivalent to 50-200mg of magnesium orotate B group vitamins in an amount of 10-500 mg, preferably 30-130mg [0039] Any suitable oral dosage form may be used, such as a tablet, effervescent tablet, capsule, liquid, suspension, powder, effervescent powder, The dosage form is preferably in the form of a capsule.
[0040] In addition to reducing the frequency and severity of headaches, especially migraine headaches, the present invention is also indicated in respect of the following conditions:
Temporary relief of headaches, _
Temporary relief of migraine headaches
Frequency of migraines
Symptomatic relief of migraine
Management of migraine
Relief of nausea and vomiting and sensitivity to light associated with migraine [0041] It is believed that Feverfew has an effect of smoothing of the muscle tissues which are involved in the inflammatory responses in the body. Feverfew also inhibits the secretion of histamine and seratonin which are involved in allergic and inflammatory responses in the body. The herb feverfew assists in inhibiting the production of prostaglandins, leukotrienes and thromboxanes which are inflammatory compounds produced by the body. The feverfew leaf powder is standardised to contain a minimum of parthenolides at 400 meg (micrograms per capsule)
EXAMPLES
[0042] The compositions of the present invention may be administered in the same way as any existing medication useful in the prophylaxis of migraine type headaches.
[0043] Once a clinician has identified or established a subject’s predisposition to headaches on the spectrum of tension headache and migraine, the subject can be introduced to the dosage form of the present invention. The dosage of the present invention can be administered as a first choice drug or it can be administered as a replacement for an existing treatment, either in response to falling efficacy or increased side effects, or as part of a predetermined regimen involving multiple therapies to minimise potential side effects and tolerance and or optimise periods where a placebo effect might be expected.
[0044] It is believed that feverfew smooths the muscle tissue involved in the body’s inflammatory response, as well as inhibiting the secretion of a range of compounds which are involved in allergic and inflammatory responses in the body such as histamine, serotonin, prostaglandins, leukotrienes and thromboxanes.
[0045] The dosage would normally be expected to be administered once daily, to best balance a proper plasma profile and patient compliance, however, the prescribed dose can be increased, decreased or divided between multiple doses in accordance with the patient’s condition and the clinician’s assessment of it.
[0046] The dosages of the present invention have been observed to be well tolerated by patients, and to demonstrate an efficacy as good as if not better than would be expected from a placebo effect in reducing the frequency and severity of tension headaches, migraines and the like.
[0047] The dosages of the present invention have also been seen to be remarkably free from side effects.
[0048] The dosage forms of the present invention are administered on an ongoing basis. The dosage forms may be administered for example at the rate of one or two capsules per day.
[0049] Components of the capsule have been used in clinical neurology practice in a sample of patients with good effects and no significant side effects. Whilst the individual components are known to have utility in headache and migraine, the unique combination of the present invention has proved to be particularly useful.
[0050] The dosage of the present invention was administered to patients and appeared to be comparable in efficacy to more conventionally prescribed medication. When regularly administered to patients, it was found to reduce the frequency and severity of migraine headaches. It was also observed that the medication of the present invention could relieve the nausea and vomiting and sensitivity to light associated with migraine headaches. It appeared that the medication of the present invention was well tolerated, and generally free from any observable side effects.
[0051] It would be expected that even if the current dosage forms only provide a particular subject with relief compatible to that of existing dosage forms, then in many cases in combination with a placebo effect, a significant portion of sufferers could achieve an effective 6-12 months of headache relief whilst being relatively free from side effects. This provides a window during which patients can recover and recuperate from the side effects of more toxic dosage regimens.
Sample formulations: [0052] The following sample formulations are provided. The dosage range of each component is also provided in column 3. Since the daily dosage is 1-2 capsules, the dosage range varies from that shown in the table up to twice that amount. The amounts may be varied independently in a dosage form, or even omitted, if required.
Formulation 1
[0052] Riboflavin has been demonstrated in the literature to be effective at 200 mg headache/migraine. The present applicant has found in clinical practice that 100 mg is also effective in this regard.
Formulation 2

Claims (5)

  1. WE CLAIM:
    1. A dosage form for reducing the frequency and severity of headaches comprising: feverfew extract containing a minimum of 400mcg parthenolides; 10-100 mg magnesium orotate; 10-200 mg riboflavin (vitamin B2); 0.1-1.0 mg folic acid (vitamin B9); 10-500 mg pyridoxine HC1 (vitamin B6); and 0.1-1.0 mg cyanocobalamin (vitamin B12).
  2. 2. A dosage form according to claim 1 comprising: feverfew extract containing a minimum of 400mcg parthenolides; about 55.4 mg magnesium orotate; about 100 mg riboflavin (vitamin B2); about 0.5 mg folic acid (vitamin B9); about 25 mg pyridoxine HC1 (vitamin B6); and about 0.4 mg cyanocobalamin (vitamin B12).
  3. 3. A dosage form according to claim 1 or claim 2 in the form of a capsule.
  4. 4. A method for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches comprising administering to a subject in need thereof a dosage form according to any one of claims 1 to 3.
  5. 5. Use of a dosage form according to any one of claims 1 to 3 for the manufacture of a medicament for the prevention of headaches, for the reduction in number of headaches or for the reduction in severity of headaches.
AU2012212380A 2011-02-02 2012-01-25 Composition and method for the treatment of headache Ceased AU2012212380B2 (en)

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Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
AU2011900328A AU2011900328A0 (en) 2011-02-02 Composition and method for the treatment of headache
AU2011900328 2011-02-02
AU2012212380A AU2012212380B2 (en) 2011-02-02 2012-01-25 Composition and method for the treatment of headache
PCT/AU2012/000054 WO2012103570A1 (en) 2011-02-02 2012-01-25 Composition comprising b group vitamins or feverfew and treatment of headaches with such compositions

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AU2012212380A1 AU2012212380A1 (en) 2013-08-22
AU2012212380B2 true AU2012212380B2 (en) 2016-12-15

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997026897A1 (en) * 1996-01-24 1997-07-31 Edwina Margaret Piper Compositions for the treatment of migraine, containing potassium, magnesium and pyridoxine
WO1999066943A1 (en) * 1998-06-25 1999-12-29 Curt Hendrix Dietary supplement for supporting cerebrovascular tone
US20040048870A1 (en) * 2002-09-06 2004-03-11 Amir Ahmad A. Composition for the prevention and treatment of migraine headaches
US20080206360A1 (en) * 2004-12-01 2008-08-28 Curt Hendrix Folate based migraine treatment
US20100284986A1 (en) * 2009-05-06 2010-11-11 Kelleher Kevin J Compositions and methods for prevention and treatment of migraines

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997026897A1 (en) * 1996-01-24 1997-07-31 Edwina Margaret Piper Compositions for the treatment of migraine, containing potassium, magnesium and pyridoxine
WO1999066943A1 (en) * 1998-06-25 1999-12-29 Curt Hendrix Dietary supplement for supporting cerebrovascular tone
US20040048870A1 (en) * 2002-09-06 2004-03-11 Amir Ahmad A. Composition for the prevention and treatment of migraine headaches
US20080206360A1 (en) * 2004-12-01 2008-08-28 Curt Hendrix Folate based migraine treatment
US20100284986A1 (en) * 2009-05-06 2010-11-11 Kelleher Kevin J Compositions and methods for prevention and treatment of migraines

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AU2012212380A1 (en) 2013-08-22

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