WO2009147467A2

WO2009147467A2 - All natural migraine remedy

Info

Publication number: WO2009147467A2
Application number: PCT/IB2008/001512
Authority: WO
Inventors: Yossi Paley
Original assignee: Yossi Paley
Priority date: 2008-06-06
Filing date: 2008-06-06
Publication date: 2009-12-10
Also published as: WO2009147467A3

Abstract

The present disclosure describes a novel liquid composition for the treatment and/or possible cure for migraine headaches and is comprised of a combination of all natural nutritional ingredients whose unique combination act synergistically to alleviate and or cure migraine headaches without any known side effects.

Description

FIELD OF DISCLOSURE

The present invention pertains to a nutritional natural liquid composition and a method for the treatment of migraine headaches.

BACKROUND OF INVENTION

Neurogenic inflammation has been postulated to be involved in a variety of human disease states and conditions, including but not limited to, migraine headaches. The basis of these conditions may be an acquired neuronal pathway that shunts neurogenic inflammatory stimuli to the cerebral vasculature. Migraine headache is a well studied disease in which neurogenic inflammation has been implicated.

According to the National Headache Foundation, one in four households in the United States, or 28 million people, is affected by migraine headaches. Of that total, 11 million people have chronic migraine headaches. Migraine headaches most commonly strike young adult women. In the world 12% of the population suffers from Migraines. The common characteristics are recurrent attacks of headache, with pain occurring most often on one side of the head, accompanied by various combinations of symptoms, such as nausea, vomiting, and sensitivity to light and sound. Migraine headaches can occur at any time of day or night, but occur most frequently occur in the morning. A migraine episode can last from several hours to several days. Migraine headaches are generally of two types: classic and common. A classic migraine headache is characterized by an "aura" (light spots) or other sensations that are known by the migraineur to occur just prior to the migraine headache itself. A common migraine headache is considered any migraine headache not preceded by an aura or other symptomatic warning to the patient. Migraine headaches are considered a hereditary disease. If both parents have migraine headaches, there is a 75% chance that the offspring will be a "migraineur"; if only one parent has migraine, the chance is as high as 50% that the offspring will be affected. During a migraine headache, blood vessels in the head go through a cycle of extreme constriction followed by rapid dilation. Nerve pathway changes and imbalances in brain chemistry may cause blood vessels to become inflamed. The interaction between the brain chemistry and blood vessel constriction/dilation is currently debated, but recent research indicates that migraine headaches are caused by alterations in the nerve pathways of the brain, specifically the trigeminal nerve system. When a migraine headache is triggered, the trigeminal nerve releases neuropeptides, such as, but not limited to, substance P and neurotransmitters such as but not limited to serotonin, bradykinin and histamine. These neuropeptides and/or neurotransmitters cause neurogenic inflammation of the brain vasculature and constriction/dilation of the blood vessels which results in migraine pain. Subsequently, trigeminal nerve endings stimulate the release of more neuropeptides and/or neurotransmitters, and a vicious cycle begins. Additionally, altered blood flow affects projections to the visual cortex and visual processing centers that may be associated with the development of aura in many migraine patients.

A variety of causal factors for migraine have been suggested that include, but are not limited to, a deficiency of cerebral magnesium, increased nitric oxide (NO) production and mitochondrial dysfunctions (J Neurol Sci 1995; 134:9). Low cerebral magnesium and/or higher NO production cause platelet aggregation with the subsequent release of serotonin and other neurotransmitters leading to cerebral constriction which may contribute to a migraine attack. Serotonin and other neurotransmitters can also stimulate the release of other pro-inflammatory agents. Furthermore, evidence indicates that impaired mitochondrial energy metabolism in the brain may play a role in the pathology of migraine headaches. Studies indicated that migraine suffers exhibited decreased mitochondrial phosphorylation between migraine attacks, indicating that the mitochondrial energy production was impaired. Specifically, a deficiency in the flavin coenzymes FAD and FMN, which are required by the flavoproteins for efficient mitochondrial electron transport chain, may be implicated in such impaired energy metabolism. In the past, treatment of migraine has involved non-pharmacologic behavioral modification and physical measures, and pharmacotherapeutic measures. Acute pharmacological drug treatment of migraine may be either to blunt the headache or to reduce the intensity of the attack. Triptans act on serotonin receptors and are currently considered the most important drugs for the acute treatment of migraine. However, when a chronic condition exists characterized by frequent attacks of debilitating pain, a preventive treatment would be desirable. Also, a significant number of patients will benefit from a combined acute and preventative treatment approach. Preventive medications are usually taken every day in order to reduce the frequency, severity and/or duration of migraine attacks. Patients may prefer such treatments since the frequently recurring migraine significantly interferes with the patients' daily routine. Currently used preventive medications include beta-adrenergic blockers, antidepressants, calcium channel antagonists, serotonin antagonists and anticonvulsants. The doses of the currently used preventative medications required to reduce the frequency of migraine may produce marked and/or intolerable side effects (Goadsby et al. NEJM 2002; 346:260). Therefore, there is a significant need for acute and preventive treatments for migraine suffers and other disease states and conditions associated with neurogenic inflammation that are devoid of said side effects. The present disclosure provides a composition useful in the treatment and/or prevention of disease states and conditions related to neurogenic inflammation. Furthermore, the present disclosure provides methods of treatment using such compositions. The compositions described are nutritional supplements which are generally recognized as safe for human consumption. Such compositions and methods have heretofore been lacking in the art.

BRIEF DESCRIPTION A]NfD BACKROUND OF PRIOR ART

Patent # US 6,465,517 describes a composition which is comprises of taurine, coenzyme Q10 and additionally creatine, L-carnitine, certain vitamins and minerals, carbohydrates, proteins, fats and herbal extracts. Patent # US 6,159,505 describes a Compositions for the treatment and prevention of migraine or stress headaches wherein there is supplied a combination of potassium, magnesium and pyridoxine optionally in association with other nutrients and/or simple analgesics. Patent* US 6,068,999 describes a dietary supplement for the support of normal cerebrovascular tone. Extracts of the feverfew plant in combination with magnesium and riboflavin, either singly or in combination provide the major therapeutic enhancement in the reduction of migraine headaches and the associated symptoms. Patent # US 5,273,759 describes An oral composition comprising in combination acetaminophen, dimenhydrinate and one or more antacid ingredients has been shown to be effective in the treatment of acute migraine attacks. Patent # US 5,538,959 describes a composition which comprises an analgesic, a magnesium salt and an effervescing agent and is admixed with or dissolved in water prior to ingestion.

Summary of Invention

The present invention embodies a liquid composition consisting essentially of a combination of natural nutritional substances which include Olive Resin, Pulverized Olive Leaves, Bay leaf Resin, Semi Dry White Wine, Rue Graveolens (Ruta), and Bay leaf Oil.

Detailed description of the Invention

The present invention is based on a particular combination of compounds, each in a particular dosage range which is made into a liquid solution. Tests have shown this combination to be uniquely effective as a dietary supplement in treating migraine headaches. Two of the active ingredients are from the olive tree one being olive resin and the second being pulverized olives leaves (Olea europaea). The cardiovascular benefits of Olive Oil are of course well known, but Olive Leaf Extract itself has been shown to lower cholesterol and benefit the heart and arteries due to its powerful anti-oxidant qualities. Southern Cross University found that the anti-oxidant activity of Olive Leaf Extract, was more powerful than green tea, and vitamins C and E (ORAC value of 10,465 mmol TE/g compared to 5,937 mmol for a green tea extract). In the late 70s, The Institute of Physiology at the Bulgarian Academy of Sciences found that the active ingredient Oleuropein, increased coronary

7 artery blood flow, and further heart benefits were noted by Dr Victor Petkov, who found that Olive Leaf Extract normalized blood pressure. A further study by the University of Milan found that Oleuropein may play a positive role in preventing the hardening of the arteries. It also acts as an Antihypertensive Animal experiments in rabbit and rat preparations found a hypotensive effect of oleuropein, possibly via direct action on smooth muscle. Oleuropeoside also may exert vasodilator activity. Additionally, olive leaf extracts may possess antispasmodic, vasodilator, and antiarrhythmic properties

The biochemical profile of olive leaves and resin include the following 1. Secoiridoidi (4 7%): oleosid, oleosid-11-metylether, ligstroside, excelsioside, ligustaloside β, morroniside, oleaceina. 2. Triterpeni (2-4%): glucosides of oleanolic acid, maslinic acid and eritrodiol. 3. Lignani: (-)-ovivyl- 4 -glucoside, (+)-acetoxypinoresinol and derivatives, cicloolivile. 4. Flavonoids: luteolin-4 -glucoside, luteolin, olivin, rutin, apigenin and derivativs. 5. Alkaloids: cinconidina, cinconina. 6. Sesquiterpene aromadendrene, eudesmina. 7. Chinoni: tannins, polyphenols acids.

The next two ingredients include Bay Leave Resin and Bay Leave Oil. Bay (Laurus nobilϊs). Bay contains compounds known as parthenolides that are extremely useful in preventing migraine. Although the mechanism of these headaches is not thoroughly understood, it appears that release of the neurotransmitter serotonin from blood cells known as platelets plays a causative role. Parthenolides inhibit serotonin release from platelets.

Feverfew (Tanacetum parthenium), which has been used traditionally for hundreds of years, is quite helpful in preventing migraine headaches. Current

8 medical research, in fact, has shown feverfew to be effective 70 percent of the time, which is a good track record, considering no remedy is effective for everyone all of the time. Patients taking a feverfew extract that contains at least 400 meg of parthenolides (feverfew's best known active ingredient) on a daily basis either stop having migraine headaches or experience less frequent and severe headaches.

Parthenolides seems to work on three levels. First, it prevents the formation of compounds like prostaglandins, leukotienes and thromboxanes, which have been shown to cause over dilation or extreme contraction of brain blood vessels. Both over dilation and contraction can cause migraines. Second, parthenolides prevents certain blood cells (platelets) from clumping which again reduces the possibility of a migraine. Third, parthenolides helps tone the muscles of the brain blood vessels so that they aren't easily bent out of shape when they become over dilated or contracted. Bay leave oil also contains methyl eugenol (4% of bay oil) and has a sedative effect.

The next ingredient is Ruta graveolens (Rue). Rue has been studied extensively. Common rue contains a mixture of furoquinoline alkaloids in a concentration of approximately 1.5%, the most important of which appear to be arborine, arborinine, and gamma-fagarine.

The acridone alkaloids (rutacridone epoxide, hydroxyrutacridone epoxide) are found in greatest concentration in the roots. Other alkaloids include graveoline, graveolinine, kokusaginine, rutacridone, and skimmianine. The flavonoid rutin is also present in the plant and is said to support and strengthen blood vessels, which reduces pressure. Ruta graveolens were also observed to inhibit the nitric oxide (NO) production by the murine macrophage cells challenged with 1μg/ml LPS when incubated simultaneously. On preincubation with the plant extract and then LPS challenge after washing the macrophage cells, only the Ruta extract were found to inhibit the NO production by 73%. Increased NO is one of the known mechanisms which have been found to be one of the causative factors in bringing on migraine headaches. Also, owing to its affinity for the nervous system, it relieves irritation and pain.

The last ingredient is Semi-Dry White Wine. This ingredient is used as a very effective transport mechanism for all the other active ingredients and allows for a very rapid absorption into the blood stream. It is of course also well known in medical physiology that alcohol easily passes the blood brain barrier and can therefore transport the active ingredients which bring relief to where it is needed most.

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References Cited

U.S. Patent Documents

Other Cited Publication References

1. Chevallier A . The Encyclopedia of Medicinal Plants . New York, NY: DK Publishing; 1996:262-263.

2. Duke J . CRC Handbook of Medicinal Herbs . Boca Raton, FL: CRC Press; 1989:417-418.

3. Minker E , Bartha C , Koltai M , Rozsa Z , Szendrei K , Reisch J . Effect of secondary substances isolated from the Ruta graveolens L. on the coronary smooth muscle . Acta Pharm Hung . 1980;50:7-ll.

4. Tyler VE . The New Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies . Philadelphia, PA: GF Stickley Co; 1987.

5. Benavente-Garcia O , Castillo J , Lorente J , Ortuno A , Del Rio JA . Antioxidant activity of phenolics extracted from Olea europaea L. leaves . Food Chem . 2000;68:457-462.

6. Zarzuelo A , Duarte J , Jimenez J , Gonzalez M , Utrilla MP . Vasodilator effect of olive leaf . Planta Med . 1991 ;57:417-419.

7. Khayyal MT , el-Ghazaly MA , Abdallah DM , Nassar NN , Okpanyi SN , Kreuter MH . Blood pressure lowering effect of an olive leaf extract ( Olea europaea ) in L-NAME induced hypertension in rats . Arzneimittelforschung . 2002;52:797-802

8. Indu Singh, Michelle Mok, Anne-Marie Christensen, Alan H. Turner, John A. Hawley. The effects of polyphenols in olive leaves on platelet function. Nutrition, Metabolism, and Cardiovascular Disease 2006; in press.

9. Tutour, B., Guedon, D. Antioxidative activities of Olea europaea leaves and related phenolic compounds. Phytochemistry 1992; 31(4): 1173-1178.

10. Cherif, S., Rahal, N., Haouala, M., et al. A clinical trial of a titrated Olea extract in the treatment of essential arterial hypertension. J. Pharm BeIg 1996; 51(2):69-71.

11 11. ISHS Acta Horticulturae 756: International Symposium on Medicinal and Nutraceutical Vlmts ANTI-INFLAMMATORY COMPOUNDS FROM MEDICINAL PLANT RUTA GRAVEOLENS

Primary Examiner: Prof. Pinchas Mandell

Attorney, Agent or Firm: Prof. Pinchas Mandell, Nissan Zafrir, Advocate

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Claims

ClaimsWe claim:

1. A method for treatment of migraine headaches which comprises orally administering a liquid solution to a person in need of such treatment which is a rapidly absorbed composition in an amount effective to relieve as well as treat symptoms of such headaches and include the possible treatment of the root cause of migraine headaches, said composition consisting essentially of a combination of natural substances which include Olive Resin, Pulverized Olive Leaves, Bay leaf Resin, Semi Dry White Wine, Rue Graveolens (Ruta), and Bay leaf Oil.

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