U.S. patent application number 10/037517 was filed with the patent office on 2002-07-25 for method for treating migraines.
Invention is credited to Imanzahrai, Ashkan.
Application Number | 20020099060 10/037517 |
Document ID | / |
Family ID | 26842539 |
Filed Date | 2002-07-25 |
United States Patent
Application |
20020099060 |
Kind Code |
A1 |
Imanzahrai, Ashkan |
July 25, 2002 |
Method for treating migraines
Abstract
This invention is a safe and effective composition and method
for treating acute migraine attacks using pseudoephedrine,
acetaminophen, and other agents in an orally administrated form to
alleviate the pain and cluster of symptoms characteristic of
migraine attacks such as nausea, photophobia, phonophobia, and
functional disabilities as well as the prodrome phase of a migraine
attack.
Inventors: |
Imanzahrai, Ashkan; (San
Jose, CA) |
Correspondence
Address: |
Kevin D. McCarthy, Esq.
Hodgson Russ LLP
Suite 2000
One M&T Plaza
Buffalo
NY
14203-2391
US
|
Family ID: |
26842539 |
Appl. No.: |
10/037517 |
Filed: |
January 4, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10037517 |
Jan 4, 2002 |
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09593238 |
Jun 14, 2000 |
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60144973 |
Jul 22, 1999 |
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Current U.S.
Class: |
514/263.31 ;
514/630; 514/649 |
Current CPC
Class: |
A61K 31/16 20130101;
A61K 31/137 20130101; A61K 31/137 20130101; A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 31/16 20130101 |
Class at
Publication: |
514/263.31 ;
514/630; 514/649 |
International
Class: |
A61K 031/522; A61K
031/137; A61K 031/16 |
Claims
We claim:
23. A method for treating migraine pain and functional disability
characteristic of a migraine attack comprising the steps of
administering to a human subject a composition comprising a
combination of pseudoephedrine, acetaminophen, and caffeine in an
amount effective to reduce the migraine pain and functional
disability characterics of a migraine attack.
25. An oral composition to treat migraines pain and other
associated symptoms comprising a medicament component consisting
essentially of pseudo ephedrine, acetaminophen, caffeine, and one
or more pharmaceutically acceptable additives selected from the
group consisting of a glidant, a lubricant, a disintegrating agent,
a filler and pigmenting material.
Description
[0001] This application claims priority as a continuation
application of U.S. non-provisional patent application Ser. No.
09/593,238 (filed on Jun. 14, 2000) which relies on the priority of
provisional patent application Ser. No. 60/144,973 which was filed
on Jul. 22, 1999.
FIELD OF THE INVENTION
[0002] The present invention relates generally to compositions and
methods used to alleviate the symptoms and pain associated with an
acute migraine attack.
BACKGROUND OF THE INVENTION
[0003] An estimated 24 to 26 million Americans--about 18% of women
and 6% of men--suffer from migraine pain and migraine-related
symptoms. (Stewart W F, Lipton R B, Celetano D D, Reed M L.
Prevalence of migraine headache in the United States: relation to
age, income, race, and other sociodemographic factors. JAMA 1992;
267:64-69.) Attacks are common, with more than 32% of sufferers
experiencing more than four episodes per month. (Rasmussen B K,
Stewart W F. The Epidemiology of Migraine. In: Olesen J,
Tfelt-Hansen P, Welch K M A, editors. The Headaches, second
edition, New York, N.Y.: Raven Press; 2000; p. 227-233.)
[0004] Migraine, a heterogeneous disorder, produces a wide spectrum
of pain and associated disabilities, both within and among
individual sufferers. The spectrum includes mild pain and no
disability in approximately 5-15% of migraine attacks, moderate to
severe pain and disability in approximately 60-70% of attacks, and
incapacitating pain and total disability in the remaining
approximately 25-35% of attacks. (Stewart W F, Schecter A, Lipton R
B. Migraine heterogeneity: disability, pain intensity, and attack
frequency and duration. Neurology 1994; 44 Suppl 4:S24-S39 and
Lipton R B, Stewart W F. Migraine in the United States: A review of
epidemiology and health care use. Neurology 1993; 43 Suppl
3:S6-S10.)
[0005] Recent population-based epidemiological studies in the
United States and elsewhere, have found that most people with
migraines are not currently consulting a physician for their
migraine attacks, and only about one-third have ever been diagnosed
by a doctor. (Edmeads J. Findlay H, Tugwell P, Pryse-Phillips W,
Nelson R F, Murray T J. Impact for migraine and tension-type
headache on lifestyle, consulting behavior and medication use: a
Canadian population survey. Can J Neurol Sci. 1993; 20:131-137;
Lipton R B, Stewart W F. Medical consultation for migraine
[abstract]. Neurology 1994; 44 Suppl 2:A199; and Rasmussen B K,
Jensen R, Olesen J, Impact of migraine on sickness, absence and
utilization of medical services: a Danish population study. J
Epidemiol Community Health 1992; 46:443-446.) The overwhelming
majority (95% of men and 97% of women) of migraineurs, i.e.,
individuals who suffer from migraines, used medication to assuage
their pain, although only about 28% of the men and 40% of the women
have ever used prescription medications. (Lipton R B, Stewart W F,
Celentano D D, Reed M L. Undiagnosed migraine: A comparison of
symptom-based and physician diagnosis. Arch Int Med 1992;
152:1273-1278; and Celentano D D, Stewart W F, Lipton R B, Reed M
L. Medication use and disability among migraineurs: a national
probability sample survey. Headache 1992; 32:223-228.) More than
90% of migraineurs use nonprescription medication for their
migraines and the majority use nonprescription medications
exclusively. (Stang P E, Osterhaus J T, Celentano D D. Migraine:
patterns of healthcare use. Neurology 1994; 44 Suppl 4:S47-S55; and
Edmeads J, Findlay H, Tugwell P, Pryse-Phillips W, Nelson R F,
Murray T J. Impact for migraine and tension-type headache on
lifestyle, consulting behavior and medication use: a Canadian
population survey. Can J Neurol Sci. 1993; 20:131-137.)
[0006] Many migraine sufferers use single-agent nonprescription
analgesics such as acetaminophen, or aspirin, or non-steroidal
anti-inflammatory agents to treat their attacks. (Lipton R B,
Newman L C, Solomon S. Over-the-counter medication and the
treatment of migraine. Headache 1994; 34:547-548.) In other
countries, a number of nonprescription drugs are specifically
approved for migraine pain. (Lipton R B, Newman L C, Solomon S.
Over-the-counter medication and the treatment of migraine. Headache
1994; 34:547-548.) The effectiveness of self-treatment of a
migraine and the effectiveness of most such nonprescription drugs
in relieving or aborting migraine pain and/or the characteristic
symptoms of a migraine has not been adequately studied in
well-controlled clinical trials. (Lipton R B, Newman L C, Solomon
S. Over-the-counter medication and the treatment of migraine.
Headache 1994; 34:547-548.) Acetaminophen, aspirin, and caffeine
are approved for relief of nonspecific headaches and tension
headaches (Migliardi J R, Armellino J J, Friedman M, Gillings D B,
Beaver W T. Caffeine as an analgesic adjuvant in tension headache.
Clin Pharmacol Ther 1994; 56:576-586), which are clinical and
physiologically distinct from a migraine.
[0007] Caffeine is widely consumed and has also been indicated for
use to treat asthma, drowsiness, fatigue, lumbar puncture headache,
and neonatal apnea. Caffeine is also an analgesic adjuvant for a
variety of pain conditions and has been included in combination
with other analgesics, ergot alkaloids, and barbiturates in
prescription formulations for a migraine. (Laska E M, Sunshine A,
Mueller F, Elvers W B, Siegel C, Rubin A. Caffeine as an analgesic
adjuvant. JAMA 1984; 251:1711-1718; Olesen J. A review of current
drugs for migraine. J Neurology 1991; 238 Suppl 1:S23-S27; Solomon
G D. Therapeutic advances in migraine. J Clin Pharmacol 1993;
33:200-209; and Sawynok J. Pharmacological rationale for the
clinical use of Caffeine. Drugs 1995; 49:37-50.) Caffeine itself
may act to relieve a migraine. Caffeine has shown to reduce
cerebral blood flow in humans and to be a nonselective adenosine
receptor antagonist. Reduction of cerebral blood flow may be due to
caffeine inhibition of the adenosine A2 receptor. (Sawynok J.
Pharmacological rationale for the clinical use of Caffeine. Drugs
1995; 49:37-50.) A2 receptors are on cerebral vascular muscles, and
act to cause vasodilation. Hence, their inhibition would have the
effect of vasoconstriction similar to other medications used to
abort the migraine headache.
[0008] Although the symptom pattern varies among migraine
sufferers, the severity of migraine pain justifies a need for
vigorous therapy in the great majority of cases. Traditional
therapy, such as ergotamine, although effective during the prodrome
phase of a migraine attack, is known to become progressively less
effective if its administration is delayed. Ergotamine is
frequently combined with caffeine, a known analgesic adjuvant, to
facilitate absorption of the ergot alkaloid. (Schmidt R, Fanchamps
A. Effect of Caffeine on intestinal absorption of ergotamine in
man. Eur J Clin Pharmacol 1974; 57:213-216.) However, repeated
dosing of ergotamine induces long-lasting and cumulative
vasoconstriction, thereby requiring careful instructions and
management of individuals who take oral preparations for migraine
attack.
[0009] Because of the cumulative toxicity of ergotamine and its
derivatives, safer therapeutics for the treatment and prophylaxis
of migraines have been sought. Examples of such ergotamine
alternatives are ergonovine, propranolol, and methysergide.
Significant toxicity, however, also occurs in nearly 40% of the
individuals who take these agents. A prescription anti-migraine
medication that is an alternative to ergotamine and its derivatives
is sumatriptan (or sumatriptan succinate), which is a selective
5-hydroxytryptamine. (Deleu D, Hanssens Y, Worthing E. Symptomatic
and prophylactic treatment of migraine: a critical reappraisal.
Clin Neuropharmacol 1998; 21(5):267-279; and Stewart W F, Lipton R
B, Celentano D D, Reed M L. Prevalence of migraine headache in the
United States: relation to age, income, race, and other
sociodemographic factors. JAMA 1992; 267:64-69.) When given early,
anti-migraine medications effectively abort the acute symptoms of a
migraine attack and the prodrome symptoms. Most of these
medications, such as ergotamine, its derivatives, and selective
5-hydroxytryptamine agonists, share the physiological property of
causing vasoconstriction. (Deleu D, Hanssens Y, Worthing E.
Symptomatic and prophylactic treatment of migraine: a critical
reappraisal. Clin Neuropharmacol 1998; 21(5):267-279.)
[0010] Thus, a clear goal in the art is to discover new, safe,
nontoxic, and effective anti-migraine drugs and treatments,
particularly nonprescription treatment medications that can be
self-administered without the need of a medical prescription.
SUMMARY OF THE INVENTION
[0011] The present invention relates to a medicinal composition for
treating individuals afflicted with pre-migraine conditions,
migraine-associated symptoms, and/or migraine pain of mild to
severe intensity. The medicinal composition comprises at least
pseudoephedrine and acetaminophen and is orally administrated.
DETAILED DESCRIPTION OF THE PRESENT INVENTION
[0012] In general, the migraine condition, with or without aura,
has a variety of characteristic features. Migraine attacks are
episodic and self-limited. The duration of untreated or
unsuccessfully treated migraine attacks can be from several hours
to several days (e.g., about four hours to about three days).
Common pain characteristics of migraines include pain in a
unilateral location, with a pulsating quality. Pain is usually of
moderate to severe intensity and is aggravated by routine physical
activity. One or more of a cluster of symptoms is recognized to
frequently accompany migraines, namely, nausea and/or vomiting,
photophobia, phonophobia, and functional disability, i.e.,
difficulty in performing routine work-related and non-work-related
tasks.
[0013] The prodrome phase of a condition of migraine occurs before
aura and before severe or throbbing migraine pain. Frequently
during prodrome, the migraine sufferer experiences mood changes,
lethargy, and tiredness. It will also be appreciated that
migrainous aura, which is experienced by about 20% of migraine
sufferers, precedes severe migraine pain and throbbing. Aura
involves distinctive auditory and visual distortions, which may
involve visual scotomas or even hemianopia and speech
abnormalities, which develop prior to severe migraine pain and
throbbing.
[0014] Medicinal treatment of migraine condition can be done during
the prodrome phase, or in the aura phase (when it occurs), which
are known to precede an acute migraine attack and migraine pain.
Generally, the acute medicinal treatment is more effective in the
prodrome phase. However, most acute medicinal treatments for
migraine such as the present invention can be administered during
the prodrome to abort the migraine attack or during the migraine
attack once the migraine pain and its other symptoms have developed
in order to reduce or eliminate migraine pain and its associated
symptoms.
[0015] As stated above, the present invention relates to a
medicinal composition for treating individuals afflicted with
pre-migraine conditions, migraine-associated symptoms, and/or
migraine pain of mild to severe intensity. The medicinal
composition comprises at least pseudoephedrine and acetaminophen
and is orally administrated. Each component of this medicinal
composition must be shown to be safe and useful in treating the
migraine complex, and evidence shows that the ingredients of the
combination can work synergistically to treat a migraine. For
example, one additional component that can be added to the
medicinal composition which adds synergistic effect is
caffeine.
[0016] The ingredients of the combination medication of
pseudoephedrine, acetaminophen, and caffeine act synergistically.
Caffeine has been shown to act synergistically with acetaminophen
to produce analgesia, (Sawynok J. Pharmacological rationale for the
clinical use of Caffeine. Drugs 1995; 49:36-50.) and to enhance the
action of other medications such as ergotamine in relieving acute
migraine attacks by increasing its absorption. (Schmidt R,
Fanchamps A. Effect of Caffeine on intestinal absorption of
ergotamine in man. Eur J Clin Pharmacol 1974; 57:213-216.)
[0017] As stated previously, caffeine itself may act to relieve the
migraine. Caffeine has shown to reduce cerebral blood flow in
humans and to be a nonselective adenosine receptor antagonist.
Reduction of cerebral blood flow may be due to caffeine inhibition
of the adenosine A2 receptor. (Sawynok J. Pharmacological rationale
for the clinical use of Caffeine. Drugs 1995; 49:37-50.) A2
receptors are on cerebral vascular muscles, and act to cause
vasodilation. Hence, their inhibition would have the effect of
vasoconstriction similar to other medications used to abort the
migraine headache.
[0018] The large arteries at the base of the brain and the pia
mater arteries make up the innervated vascular system of the
cerebral vessels, which has a rich adrenergic nerve supply and
responds to catecholamines. These vessels would vasoconstrict in
response to sympathomimetic drugs such as pseudoephedrine. The
non-innervated vascular system is connected serially to the first,
consisting of parenchymal arteries and terminal high resistance
arterioles. The newer theories about pathogenesis of migraine
complex describe that in susceptible individuals trigger factors
set off a series of local and systemic events that initiate both
focal and generalized manifestation of the migraine. Generally, an
initial vasoconstriction phase occurs locally and predominantly in
the unilateral cerebral vessels. This unilateral vasoconstriction
is associated with aura in cases of a classic migraine. The
vasoconstriction is followed by reflex vasodilation due to local
anoxia, acidosis, and systemic drop in serotonin. Marked
vasodilation with accumulated vasoactive substances sensitizes the
pain receptors in the blood vessels and produces a sterile
inflammation. These changes along with the vasodilation cause the
pain in migraine. (Seymour D. Head Pain Diagnosis and Management.
Clin Symp 1994; 46(3):2-34.)
[0019] Abortion of a migraine headache is thought to be achieved by
vasoconstriction of dilated intracranial and extracranial vessels
since vasodilation is associated with the headache phase. (Seymour
D. Head Pain Diagnosis and Management. Clin Symp 1994; 46(3):2-34.;
Godsby P J. Mechanism and management of headache. J R Coll
Physicians Lond May/June 1999; 33(3):228-234; and Sawynok J.
Pharmacological rationale for the clinical use of Caffeine. Drugs
1995; 49:37-50.) Vasoconstriction produces reduction in blood flow.
For example ergotamine and sumatriptan produce vasoconstriction of
cranial blood vessels. (Deleu D, Hanssens Y, Worthing E.
Symptomatic and prophylactic treatment of migraine: a critical
reappraisal. Clin Neuropharmacol 1998; 21(5):267-279.) The
termination of the headache is achieved 1) by restoring the loss of
homeostasis of blood supply to the brain to reduce the sterile
inflammation caused by vasodilation and 2) by reducing the
vasodilated vessels closer to a normal state that would directly
decrease the sensation of pain in the innervated vessels.
[0020] Caffeine and pseudoephedrine may have a synergistic affect
on cerebral vasoconstriction, since pseudoephedrine acts as an
agonist directly on both alpha and, to the lesser degree,
beta-adrenergic receptors. Activation of alpha-adrenergic receptors
on vascular smooth muscles causes vasoconstriction. (Seymour D.
Head Pain Diagnosis and Management. Clin Symp 1994;
46(3):2-34.)
[0021] Acetaminophen has been routinely used to treat mild to
moderate migraines. (Godsby P J. Mechanism and management of
headache. J R Coll Physicians Lond May/June 1999; 33(3):228-234;
and Deleu D, Hanssens Y, Worthing E. Symptomatic and prophylactic
treatment of migraine: a critical reappraisal. Clin Neuropharmacol
1998; 21(5) :267-279.)
[0022] Turning to the present invention and study, a hand full of
migraine patients were treated privately with the combination of
pseudoephedrine 60 mg and acetaminophen 1000 mg every six (6)
hours. These patients reported a reduction of their migraine
symptoms such as headache, nausea, phonophobia, and photophobia in
2 hours after treatment, as compared to acetaminophen alone. Most
cases of migraine attack were completely aborted after one or two
treatments (see Table 1).
1TABLE 1 Severity of Severity of headache on a headache on a Other
Relief scale of 1-10, scale of 1-10, symptoms of other before the
after the besides symptoms Age Sex medication medication headache
achieved 29 F 8 Completely Photo All relieved and relieved Phono 34
M 6 Completely Photo, All relieved nausea, relieved and Phono 31 F
9.5 Completely Photo, All relieved nausea, relieved and Phono Notes
on Table 1: Age is given in years. M = male. F = female.
[0023] Medication is pseudoephedrine 60 mg and acetaminophen 1000
mg, given once, after one episode of a migraine attack.
[0024] Photo=photophobia.
[0025] Phono=phonophobia.
[0026] Nausea
[0027] Pseudoephedrine has been shown to be effective in treating
migraine patient's cardiovascular abnormalities. A study was done
on cardiovascular reflex response in migraine patients. (Munari L,
Milaneri I, Silvani A, Bussone G, Bioardi A. Pharmacologic
evaluation of cardiovascular reflex responses in migraine patients:
lack of central sympathetic modulation. Funct. Neurol. 1989;
4(4):375-378.) Pretreatment with 2 mg/kg abolished the effects of
lower blood pressure after sustained handgrip that is seen in
migraine patients versus normal patients. This was statistically
significant data (p<0.05). Pretreatment with 2 mg/kg abolished
effects of increased postural hypotension that is seen in migraine
patients versus normal patients. This was statistically significant
data (p<0.05).
[0028] The components of this medication are relatively safe and
with few side effects. Each component of this medication has been
available as an over-the-counter medication in the US for other
uses than the scope of this invention.
[0029] The uses of the combination pseudoephedrine and
acetaminophen have included treatment of the symptoms associated
with common cold, nasal congestion, sinus congestion, and sinus
pain symptoms, but not migraine symptoms. Some examples of the
brand names of these types of medication are Sudafed.RTM. Sinus
Maximum, Alka-Seltzer.RTM. Plus Cold-Sinus Medicine Liqui-Gels,
Infants' Tylenol Cold Decongestant & Fever Reducer, and
Excedrin.RTM. Sinus.
[0030] Acetaminophen has been widely used since the 1950s.
Acetaminophen has been used alone for arthralgia, dental pain,
dysmenorrhea, fever, headache, mild pain, myalgia, and
osteoarthritis. Although, acetaminophen has been used for migraine
pain, it has not been used in combination with pseudoephedrine or
pseudoephedrine and caffeine. Acetaminophen has proven to be safe
and with very few side effects compared to the group of NSAID
analgesics. (Clissold S P., Pharacetamol and phenacetin. Drugs
1986; 32 Suppl 4:315-321.)
[0031] Also, pseudoephedrine has been widely used and shown to be
safe and with few side effects. Pseudoephedrine has been mainly
used to treat nasal congestion. (Hughes D T D, Empey D W, Land M.
Effects of pseudoephedrine in man. Journal of Clinical and Hospital
Pharmacy 1983; 8:315-321.)
[0032] Caffeine is widely consumed and has also been indicated for
use to treat asthma, drowsiness, fatigue, lumbar puncture headache,
and neonatal apnea.
[0033] The length of time that acetaminophen, pseudoephedrine, and
caffeine have been on the market with relatively few side effects
has demonstrated their excellent safety profiles.
[0034] The present invention is the medicinal composition for
treatment of migraine complex symptoms. The medicinal composition
is an oral medication of pseudoephedrine and acetaminophen, or
pseudoephedrine, acetaminophen, and caffeine. Such oral
formulations would be in a liquid, solid, or gelatin (semi-solid)
form such as an elixir, pill, or capsule. Without limiting the
scope of the present invention, an oral dosage of the combination
medication may, for example, compromise;
EXAMPLE 1
[0035] A single solid or liquid dosage form comprise of
pseudoephedrine in an amount of from about 30 mg to about 60 mg,
acetaminophen in an amount of from about 200 mg to about 1000 mg,
and caffeine in an amount of about 40 mg to about 100 mg; or
EXAMPLE 2
[0036] A single solid or liquid dosage form comprise of
pseudoephedrine in an amount of from about 30 mg to about 60 mg,
and acetaminophen in an amount of from about 200 mg to about 1000
mg.
[0037] The dosage specified in Examples 1 and 2 can be taken every
6 hours by mouth. This dosage is in agreement with the
over-the-counter recommended dosages of the pseudoephedrine,
acetaminophen, and caffeine.
[0038] Without limiting the scope of the present invention, in the
composition of these vehicles to administrate the active
medications of pseudoephedrine and acetaminophen, and
pseudoephedrine, acetaminophen, and caffeine, acceptable additives
may be added if desired. The acceptable additives may be in the
group of glidants, lubricants, disintegrating agents, coloring
agents, and fillers. Examples of these acceptable additives are
pregelatinized starch, magnesium sterate, microcrystalline
cellulose, croscarmellose sodium, D&C yellow #10, and colloidal
silicon dioxide.
[0039] In conclusion, the present invention relates generally to
compositions and methods used to alleviate the symptoms and pain
associated with acute migraine attacks. More particularly, the
present invention relates to the use of a combination of
pseudoephedrine and acetaminophen with optional caffeine, and is
orally administrated for treating individuals afflicted with
pre-migraine conditions, migraine-associated symptoms, and/or
migraine pain of mild to severe intensity. The combination
pseudoephedrine and acetaminophen with optional caffeine is a new,
effective, and convenient medication to treat acute migraine
attacks. Each of the ingredients of this combination has been shown
to be useful in treating the migraine complex. Evidence shows that
the ingredients of the medicinal combination work synergistically
to treat migraine.
[0040] While preferred embodiments of the present invention have
been disclosed, it will be appreciated that it is not limited
thereto but may be otherwise embodied with the scope of the
following claims.
* * * * *