BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention is directed to the field of pharmacognosy and particularly to the formulation of aqueous herbal supplement compositions for providing relief to a user suffering from migraine headaches.

2. Background Art

Migraine is a common neurological syndrome that has been diagnosed in more than 28 million Americans. Migraine is a chemical disorder of the brain which generates an "electrical storm" that slowly spreads from one part of the brain to another. Three out of every four migraine sufferers is a woman and the syndrome is inheritable. Acute migraine symptoms can be effectively treated by prescription medications. However, many patients are reluctant to use prescription drugs for long term prevention of migraine. Despite this reluctancy, much of the public appears open to the use of alternative medical treatments, including herbal medications in particular, for long term prevention.

Migraine can include any number of symptoms including recurrent headaches, nausea, photophobia (sensitivity to light), and phonophobia (sensitivity to sound). The headaches associated with migraine can be either unilateral (focused on one side) or bilateral. They can be severe and involve throbbing pain. It is also not uncommon for patients to complain of a band like "pressure" around the head and neck. Additionally, the scalp may be tender and the patient may experience chronic nasal congestion and stuffiness. Other symptoms include pain behind they eye, inside the ear, or near the tooth. The dominant symptom is often neck stiffness, which can lead doctors to mis-diagnose the condition as cervical disc disease or cervical arthritis. Environmental factors including temperature and humidity along with certain foods— often coffee, chocolate, aging cheese and red wine— can trigger migraine. Emotional stress, lack of sleep, and not eating at proper times (hypoglycemia) can also be the cause of a migraine attack. The trigger factor causes release in the brain of a variety of chemical substances (peptides), the most important ones being CGRP ( Calcitonin Gene Related Protein) Substance P, and Bradykinin. These are vasoactive peptides which cause dilatation and/or constriction of blood vessels. The serotonin receptors located along the inner lining of the blood vessels in the brain and in the coverings (meninges) of the brain play an important role in the genesis of the symptoms of migraine, headache, of course, being the most prominent. Other neurotransmitters are also implicated during a migraine. Release of nor-epinephine causes fast heart rate, sweating, and a sense of anxiety. All of these neurotransmitters are effectively blocked by beta blocker drugs. Dopamine release could cause signs of acute depression, nausea, and vomiting. The drug metachlorpramide (Reglan) blocks these effects. Other neurotransmitters like glutamate and Gaba Amino Butyric Acid (GABA) are also implicated in the pathophysiology of migraine.

Migraine symptoms are notoriously recurrent. Many times, patients begin to suffer from migraine during the early childhood or teenage years, when they are often dismissed as sinus, tension or allergy headaches. The repeated occurrence of headaches (one sided or both sides), light sensitivity, sound sensitivity, odor sensitivity (osmophobia), nausea, nasal stuffiness, neck stiffness, and scalp tenderness can indicate that a headache is caused by migraine. Because the syndrome is often inherited, positive family history helps to confirm the diagnosis. Additionally, many women experience a migraine headache just before or during the menstrual period, a characteristic not seen in other types of headaches.

Compositions formulated to alleviate the symptoms associated with Migraine headaches are known in the art. Patents in this field have disclosed a number of different formulations for providing relief to users afflicted with the symptoms of Migraine headaches. Furthermore, there are a variety of patents which discuss some of the components mentioned herein. Examples of some can be found in the following U.S. patents: 4,758,433; 4,962,121; 6,038,999; 6,312,736; 6,403,116; 6,465,517; 6,500,450; 6,642,243; 6,770,263; 6,967,033; 7,018,983; and 7,192,614.

SUMMARY OF THE INVENTION

The present invention is directed to providing an aqueous herbal supplement composition that is formulated to effectively relieve a user's migraine headache symptoms. The present invention generally provides an aqueous herbal supplement composition specifically formulated to alleviate a number of the symptoms experienced by those suffering from migraine and to reduce the risk of their recurrence. It is an aspect of the invention to provide an aqueous herbal supplement composition comprising natural ingredients chosen.

According to a first aspect, the present invention relates to an aqueous herbal supplement composition comprising Ubiquinone, Feverfew extracts, and Magnesium salt.

According to another aspect, the present invention relates to an aqueous herbal supplement composition comprising Ubiquinone, Feverfew extracts, Magnesium salt, and Butterbur extracts.

According to still another aspect, the present invention relates to an aqueous herbal supplement composition comprising Ubiquinone, Feverfew extracts, Magnesium salt, and St. John's Wort extracts. According to yet another aspect, the present invention relates to an aqueous herbal supplement composition comprising Ubiquinone, Feverfew extracts, Magnesium salt, and vitamin B2.

According to still another aspect, the present invention relates to an aqueous herbal supplement composition comprising Ubiquinone, Feverfew extracts, Magnesium salt, Butterbur extracts, and vitamin B2. According to yet another aspect, the present invention relates to an aqueous herbal supplement composition comprising Ubiquinone, Feverfew extracts, Magnesium salt, St. John's Wort extracts, and vitamin B2.

According to yet another aspect, the present invention relates to an aqueous herbal supplement composition comprising Ubiquinone, Feverfew extracts, Magnesium salt, Butterbur Root extracts, and St. John's Wort extracts.

According to yet another aspect, the present invention relates to an aqueous herbal supplement composition comprising Ubiquinone, Feverfew extracts, Magnesium salt, Butterbur extracts, St. John's Wort extracts, and vitamin B2. According to still yet another aspect, the present invention relates to an aqueous herbal supplement composition which can further optionally include sweeteners, natural flavorings, and preservatives.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT(S) Reference will now be made in detail to presently preferred compositions, embodiments and methods of the present invention, which constitute the best modes of practicing the invention presently known to the inventor. However, it is to be understood that the disclosed embodiments are merely exemplary of the invention that may be embodied in various and alternative forms. Therefore, specific details disclosed herein are not to be interpreted as limiting, but merely as a representative basis for any aspect of the invention and/or as a representative basis for teaching one skilled in the art to variously employ the present invention.

Except in the examples, or where otherwise expressly indicated, all numerical quantities in this description indicating amounts of material or conditions of reaction and/or use are to be understood as modified by the word "about" in describing the broadest scope of the invention. Practice within the numerical limits stated is generally preferred. All concentration values and ranges appearing in this application are to be understood as contemplating solutions in which water is the primary component, whether or not the term "water" or "aqueous" is used in describing the concentration. Also, unless expressly stated to the contrary: percent, "parts of," and ratio values are by weight; description of a group or class of materials as suitable or preferred for a given purpose in connection with the invention implies that mixtures of any two or more of the members of the group or class are equally suitable or preferred; description of constituents in chemical terms refers to the constituents at the time of addition to any combination specified in the description, and does not necessarily preclude chemical interactions among the constituents of a mixture once mixed; the first definition of an acronym or other abbreviation applies to all subsequent uses herein of the same abbreviation and applies mutatis mutandis to normal grammatical variations of the initially defined abbreviation; and, unless expressly stated to the contrary, measurement of a property is determined by the same technique as previously or later referenced for the same property.

A novel herbal supplement composition for providing symptomatic relief to a user suffering from migraine is provided. The aqueous herbal supplement composition is formulated to alleviate migraine symptoms and to provide continued defense against recurrence of those symptoms. These symptoms often include headaches, light sensitivity, sound sensitivity, odor sensitivity, nausea, nasal stuffiness, neck stiffness, and scalp tenderness. The present invention provides an aqueous composition that a user can consume during the course of the migraine in order to alleviate the symptoms and to help protect against their recurrence. Additionally, it is one aspect of the invention to use natural, FDA-approved active ingredients— also referred to herein as "constituents"— in the formulation of the aqueous herbal supplement composition.

According to at least one aspect, the aqueous herbal supplement composition comprises Ubiquinone, Feverfew extracts, and Magnesium salt. These three constituents are described more specifically below. The following table provides at least certain embodiments of the amount of each specific constituent: CONSTITUENT AMOUNT

Ubiquinone 200-400 mg

Tanacetum Parthenium 0-1.0 mg

Magnesium Citrate 250-500 mg

Vitamin B2 2.0-8.0 mg

Petasin 7.0 mg

Isopetasin 7.0 mg

Hypericin 10 mg

Hyperforin 750 mg

In at least certain embodiments, the present invention relates to the use of the Co-enzyme-Q-10, which has distinct and pharmacologically well recognized roles to play in the treatment of migraine and a combination of six other medications, all naturally available, and OTC (Over The Counter), in varying combinations.

The dosages mentioned herein are not necessarily fixed regimens, and in practical use, could be used in higher or lower dosages of each drug. Also, these six drugs could be used in combinations of all six drugs, less than six drugs, for example: two, three, four, or five drugs in combination, or more than six drugs. The ingredients of this " Migraine Herbal Tonic" would be: the Co-enzyme-C-10 plus a formulation of various components including:

A. extracts from Feverfew;

B. an extract of St. John's Wort;

C. extracts from Butterbur Root;

D. magnesium Citrate as the salt of preference; and

E. riboflavin known as vitamin B2.

The Co-enzyme C-10 (CoQIO) known as Ubiquinone, is essentially a vitamin or vitamin-like substance. Vitamins are as organic compounds essential in minute amounts for normal body function, acting as co-enzymes or precursors to co-enzymes. The biosynthesis of CoQIO from the aminoacid tyrosine, is a complex process involving at least eight vitamins and several trace elements. Co Q10 is the coenzyme for at least three mitochondrial enzymes ( complexes 1, II and III). Mitochondrial enzymes of the oxidative phosphorylation pathway are vital for the production of high energy phosphate and adenosine triphosphate (ATP) upon which all cellular function depend. The electron and proton transfer functions of the quinine ring are of fundamental importance to all forms of life. In its reduced form CoQIO is a potent antioxidant.

Co Q10 was first isolated in 1957. In 1958, the chemical structure of Co Q10 was defined as : 2,3 dimethoxy-5 methyl-6 decaprenyl benzoquinone, and was first synthesized by fermentation process. In 1960, Co Q7 was used in clinical practice to treat patients with congestive heart failure. In 1966, it was demonstrated that reduced form of CoQIO is an effective anti-oxidant. In the 1970's CoQIO deficiency in human heart disease was documented. In 1978 Peter Mitchell received the Nobel Price for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory, which includes the vital protonmotive role of CoQIO in the energy transfer systems.

Since the Japanese were able to produce CoQIO in commercial quantities, its value in clinical medicine has been documented by clinical trials in Heart failure, Cancer, AIDS, Parkinson's Disease, prevention of Atherosclerosis and in immunological diseases. Scientists believe, the clinical applications of CoQIO is only just emerging and it holds the potential to alter our current thinking of therapeutics.

The Role of CoQIO in treatment of Migraine is just being documented (Neurology Feb: 2004). Its role as a free radical scavenger, antioxidant, mediator of energy transfer and stabilizing cell membranes and mitochondria, all may be at play in its role as a treatment for migraine. CoQIO was initially used in doses of 30 to 45 mg per day in the trials for congestive heart failure. In this invention I am proposing Ubiquinone (Co-enzyme-Q-10) as the foundation and main ingredient, in combination with other components. The Co-enzyme-Q-10 Uniquinone has the major role to play in the proposed migraine preventive herbal combo: " Migraine Tonic" and is to be administered in the amount of 200 - 400 mg. per unit dose of the formula combination.

The extract of Feverfew to be used is from an extracted group called Parthenolides. The botanical name of Feverfew is Chrysanthemum parthenium and its medical extract is a Parthenolide. The group of Parthenolides are sesquiterpene lactones which are found in Feverfew and the particular Parthenolide to be used is known as Tanacetum parthenium.

The feverfew plant is a perennial herb with an erect, branched, downy and leafy stem and many alternate, yellowish, pinnate to bi-pinnate leaves. The fruit is a ribbed achene without pappus; all components of this plant is strongly aromatic. This plant is available in most of Europe including the British Isles and also the Mediterranean region.

The common name Feverfew, is a corruption of the Latin word "febrifugia", an implication of the plants use formerly, as a febrifuge: fever reducing medication. An infusion of the dried herb was used as a stomachic, sedative, disinfectant, and anti-spasmodic. Very recently Feverfew has been given attention as a migraine drug, especially in Britain, where it is being studied in clinical settings. It's migraine relieving effect could be attributed to its action as an antagonist to prostaglandins, an inflammation causing peptide. Protaglandins are implicated in the perpetuation of aseptic inflammation of the meninges ( coverings of the brain) and other tissues around the head and neck, causing migraine headache to continue for days. The amount of natural or laboratory produced Tanacetum parthenium to be used is 1.0 mg or less per dosage unit. However, since some findings indicate that the extract from feverfew should not be taken in pregnancy, an alternate formulation found within this invention should be utilized for women in pregnancy. The extracts of St. John's Wort that are known to treat migraine are Hypericin and Hyperforin. One of the aftermath and /or co-morbidity of migraine is depression. The chemical substrate for this is the low serotonin levels in the brain, which results from repeated episodes of migraine. Excretion of serotonin metabolites in the urine are significantly elevated during a migraine attack, indicating rapid turnover of serotonin reserves in the brain. In patients with an inherent propensity for depression, (endogenous depression) the serotonin depletion could precipitate and perpetuate depression, unless the levels are corrected by treatment. The majority of patients with migraine related depression have mild or moderate depression. Cases with severe depression, must be treated seriously by an experienced psychiatrist.

St. John's Wort is a perennial herb with a stout creeping rhizome which bears clumps of erect branched stems. It is commonly seen throughout Europe, including Britain. Its name starting as "St. John's" came from the fact that the plant was used by the Knights of St. John of Jerusalem to heal the wounds of Crusaders. The flowering stem is used in medicine. Their components include tannins, and flavonoid glycosides like hypericin, hyperflorin, rutin, and catechol and resins. It has been used to treat chronic inflammation, and menstrual disorders. This plant has been used for medicinal purposes for some 2000 years.

Recently there has emerged great interest in St. John's wort, as an anti-depressant. It has been a popular anti-depressant for more than 15 years in Europe, in Germany alone physicians write 3 million prescriptions a year; this is 25 times more than the number of prescriptions they write for Prozac.

St. John's Wort is getting attention in the U.S. as well: it has been called "the premier herb for treating moderate depression". In 1994, the prestigious Journal of Geriatric Psychiatry and Neurology, devoted an entire issue containing 17 research articles on St. John's Wort. One study tracked the herb's effect on 3,250 patients with mild to moderate depression. 80% either felt better or became completely symptom free after four weeks of treatment. In an article published in British Medical Journal in August of 1996, 23 controlled studies involving 1757 depressed patients were reviewed: the conclusion was St. John's Wort worked nearly 3 times better than placebo.

St. John's is believed to be safe. In a study of 3, 250 depressed patients, only 2.4% experienced side effects, which included restlessness, gastrointestinal irritations, and mild allergic reactions. In has been noted that the common prescription antidepressants like Prozac, causes more serious side effects than this herb. However, there is concern high doses of this herb could cause photosensitivity, like in sheep who ingested large quantities of St. John's Wort. No one has reported photosensitivity in patients using this herb for depression. The dosages indicated for this invention are 10 mg. or less per unit dose or Hypericin and/or 750 mg. or less per unit dose of Hyperforin either naturally extracted or laboratory synthesized.

The extracts of St. John's Wort may cause increased sensitivity to sunlight. Other side effects can include anxiety, dry mouth, dizziness, gastrointestinal symptoms, fatigue, headache, or sexual dysfunction.

Research shows that St. John's Wort interacts with some drugs. The herb affects the way the body processes or breaks down many drugs; in some cases, it may speed or slow a drug's breakdown. Drugs that can be affected include:

antidepressants;

birth control pills;

cyclosporine, which prevents the body from rejecting transplanted organs;

digoxin, which strengthens heart muscle contractions; indinavir and possibly other drugs used to control HIV infection; irinotecan and possibly other drugs used to treat cancer; and warfarin and related anticoagulants.

When combined with certain antidepressants, St. John's Wort may increase side effects such as nausea, anxiety, headache, and confusion. For the above specific cautions indicated, it is therefore advised that an alternate formulation within this invention be utilized that does not include the extracts of St. John's Wort.

The extracts of Butterbur root are Petasin and Iospetasin. A perennial herb with a creeping horizontal rhizome, seen to sprout in early spring. This herb grows throughout in Europe, including British Isles. The name Butterbur came from the fact its large leaves were once used to wrap up butter in hot weather. The roots are mainly used in treatment of migraine. In the Homeopathic Pharmacopia, the tincture of the fresh plant is used to treat "neuralgia". A clinical study of the root of Butterbur was published in the popular journal NEUROLOGY on December 2004. 254 migraine patients with two to six attacks per month were studied with a dosage regimen of 75mg twice daily over a period of 4 months. 48% reduction of headache frequency was noted, which was statistically significant, and more effective than placebo. The drug was well tolerated.

It must be remembered that the extracts for use in this invention come from the root of Butterbur only and not from any other component of the plant. The natural extract of Petasin and/or Isopetasin or the laboratory synthesis of these extracts are to be used in dosages of 7 mg. or less of each per unit dose. The Magnesium salt known as Magnesium Citrate. Magnesium is an element ( Mg) with an atomic number 12 and atomic weight of 24.3050. It oxidizes to magnesia, a bio-element and it's many salts have clinical applications.

Magnesium plays an important role in membrane physiology, in maintaining membrane electrical polarity and calcium ion transport across cell membranes. Its deficiency causes seizures in humans. It is essential for cardiac conduction of electrical impulses, skeletal muscle relaxation and neuro-chemical transmission. In the brain, decrease in mg levels causes neuronal irritability and excitation, leading to frank "electrical storm" or seizure activity. One of the current views on migraine is, it is a clinical phenomenon of neuronal excitation, the emerging electrical excitation spreads as a "wave" from one pole of the brain to the other. Migraine patients experience often, loss of speech, numbness of one side of face, then arm, body and lower limb. The cause of this "march" of migraine symptoms is attributed to the "spreading wave of excitation" generated by one group of neurons. It is noteworthy Living speculated in 1873, migraine is a "nerve storm".

Use of magnesium is useful to control this neuronal excitability, which is one factor that perpetuates migraine. I have used it as an intravenous injection in intra-partum ( in labor) and post-partum( after delivery) women suffering from severe migraine, with dramatic effect. In this invention the unit dosage of Magnesium Citrate to be used is 250 to 500 mg. per total formulation dosage.

The vitamin B2 known as Riboflavin. Riboflavin is a water soluble, heat stable, factor of the Vitamin B -Complex. Components of this vitamin are co-enzymes of the flavodehydrogenases, which plays important role in oxidative metabolic pathways, generating enery bonds. Daily requirement for adult men is 1.7 mg and for adult women 1.3 mg. Higher doses are required during pregnancy and lactation. Dietary sources include, green vegetables, liver, kidney, wheat germ, diary products, and fish. A deficit of mitochondrial energy metabolism is considered to play a role in the genesis of migraine. Riboflavin plays a vital role in mitochondrial oxidative metabolism. Riboflavin is also considered to have an anti-inflammatory effect, by inhibiting the inflammatory peptide, prostaglandin. These hypotheses was tested with several clinical trials, both in the U.S and in Europe. Patient' improvement in migraine headache were statistically significant. Prediction is riboflavin would take a key role in the control of migraine. Dosages to be used in this invention are from 2 to 8 mg. of Riboflavin (vitamin B2) per unit dose of formulation.

According to another aspect of the present invention, the aqueous herbal supplement composition may include one or more sweeteners. Possible sweeteners for use with the present invention include sugar, sugar alcohols, syrup, honey, and molasses. As used in the claims, the term "sugar" is to be understood to refer to any type of culinary sugar including, but not limited to, granulated sugar, white refined sugar, brown sugar, sugar cane, bianco directo, raw sugar, and mill white sugar. The broad term "syrup" is used herein to represent any of the following types of syrup, or combinations thereof: maple syrup, simple syrup, corn syrup, gomme syrup, palm syrup, or birch syrup. Common sugar substitutes, such as saccharin, aspartame, sucralose, neotame, and acesulfame potassium, may alternatively be used as an optional sweetener for embodiments of the present invention. As used in the claims, the term "sugar substitute" shall indicate any of the common sugar substitutes including saccharin, aspartame, sucralose, neotame, and acesulfame potassium.

Embodiments of the present invention may optionally include natural flavorings for taste. The natural flavorings utilized by the present invention may include any types commonly known in the art.

Embodiments of the present invention may optionally include preservatives. The preservatives utilized by the present invention may include any type commonly known in the art.

The aqueous herbal supplement compositions of the present invention may be prepared by any suitable preparation method known in the art. A non-limiting, representative example of such a method is hot-water extraction which involves any comminution means, such as slicing or grinding, followed by dissolving the active ingredients in boiling water. Additionally, suitable methods may include an irradiation step following extraction in order to ensure sterility of the end product. Furthermore, the embodiments of the present invention disclosed in this application are not meant to be limited to any specific method of preparation. While aspects of the invention have been illustrated and described, it is not intended that these aspects illustrate and describe all possible forms of the invention. Rather, the words used in the specification are words of description rather than limitation, and it is understood that various changes may be made without departing from the spirit and scope of the invention.