KR0128705B1 - Pharmacentical composition for headache - Google Patents

Abstract

The prevention and cure composition of headache contains vitamin E. More desirably, the composition contains more than 1 or 2 components selected from group composed of vitamin C and vitamin B. Accordingly, this composition shows effect on the prevention or treatment of tonic headache and megrim .

Description

Headache prevention and treatment composition

Figure 1: Schematic diagram showing the change in intensity and progression of headache over time

FIG. 2: A graph measuring serum free fatty acid before and after shooting in shooting athletes

Fig.3: Graphs measuring lipid peroxide in serum before and after shooting

1) The gist of the invention

The present invention relates to a composition for preventing and treating headaches, characterized by containing vitamin E. More particularly, the present invention relates to a composition for the prevention and treatment of headaches, in particular tension headaches and migraines, further comprising one or more components selected from the group consisting of vitamin C and vitamin B and also methionine. .

2) motivation of invention

Headache is a type of pain associated with the head surface in pain irritation to deep intracranial tissue. The brain tissue itself does not cause pain even if it is damaged, but a headache occurs when the artery is pulled, the tentorium is damaged, or when the dura is extended to the bottom of the brain. Pain (1993). p.83-99].

Headaches include tension headaches and migraine headaches, accounting for about 80% of the total headaches [Reference: 綜合 醫學 社, 今 月 の 冶療 (頭痛 の 治療). 1993 (June), p36] Other 20% of headaches may be divided into various details depending on the cause [Olesen, J et al., Basic mechanisms of headache (1988), p464-474, The Netherlands]. . It is also thought to separate cluster headache from migraine headaches. However, unless there is a clear cause, most of them are caused by stress, and stress headaches can be seen in both of the above.

The intensity of the headache can be represented by the shape in Figure 1 below. In other words, at first, the pain level increases rapidly, reaching a peak, and over time, the headache calms down and slowly subsides.

These headaches are experienced by more than 90% of people, and migraine headaches represent 5% of the population. Migraine headaches are caused by persistent vasospasm in some of the head's arteries when mental tension or emotional state persists, causing partial oxygen deficiency in the supply section of the heat tube that causes cramps. Due to severe oxygen deficiency, blood vessels cannot maintain tension for a long time, and blood vessels are tensioned and pulsated strongly by blood pressure, resulting in excessive extension of the arterial wall. However, in the case of headaches and migraines, the exact cause is not yet known and its detailed route is unknown. [Reference: Lee Eun-ok et al., Pain (1993).新光 出版社. p.83-99].

The food we consumed is produced by several stages of oxidation in the cell and the electrons (e-) eventually form the nicotinamide adenine dinucleotide reduced form (NADH) or the flavor adenine dinucleotide reduced form (FADH). It enters oxygen and in the process produces energy through ATP (adenosine-5-tri phosphate). For this energy generation, large free radical species are created when they are responsive to the oxidation reaction by electrons.

Among these active oxygen, superoxide anion radical (O ₂ ^_ ), perhydroxy radical (HO ₂ ^_ ), hydrogen peroxide (H ₂ O ₂ ), hydroxy radical (HO ^_ ), singlet oxygen ( ¹ O ₂ ), hyper Chlorite (OC ^_ ), hydroxyperoxide (RCOOH), peroxy radicals (RCOO ^_ ) or alkoxy radicals (RO ^_ ), and these free radicals denature and destroy many of the key substances needed to maintain function in vivo The damage is so small that the effect is not detected externally, but if it accumulates for a long time, it causes aging and promotes various diseases [Reference: 大 柳 善 彦, SOD と 活性 酸 表調節 制 (1989), 日本 醫學 館, p. 3-6].

On the other hand, biological tissues also have an effective defense against free radicals. The active radical produced by the reduction of molecular oxygen (O ₂ ^_ ) is converted into hydrogen peroxide (H ₂ O ₂ ) by the superoxide dismutase enzyme, which is then hydrated by catalase. It becomes a hydroxy radical (OH ^_ ) and turns into water (H ₂ O). Hydrogen peroxide can also be converted to water by glutathione peroxidase.

The brain is only 2% of the body weight, but the energy consumption is 18% [Reference: 中 川 八 郞, 腦 の 營養 (1992).共 立 出版. p.6-18], uses glucose as the main energy source. In muscle, anaerobic metabolism, which does not require oxygen, breaks down glucose into lactic acid for energy, whereas the brain undergoes aerobic metabolic processes that require oxygen. Therefore, glucose in the brain cells through the TCA cycle (tricarboxylic acid cycle) through the process through the mitochondrial electron transfer system to obtain energy, the physiological characteristics of the brain, a lot of free radicals It is very likely to be generated.

When the living body is stressed, the nerves and the endocrine system responds to external stimuli. The activity of the sympathetic nervous system is primarily increased, thereby promoting the secretion of epinephrine and noepinephrine. In addition, an increase in corticosteroids in the blood is a notable response. These reactions are consistent with stress, where epinephrine causes hepatic gluconeogenesis to increase blood sugar, and noepinephrine stimulates adipose tissue to cause lipolysis to increase free fatty acids. [Reference: Dimsdale, JE et al., JAMA., 243 (4), p. 340-342 (1980); Qurice, C.M. et al., Llfe Sci., 28, p. 1897-1902 (1981).

It is also reported in the US Food and Agriculture Organization (FA.O., Energy and protein requirement, 1985) that stress increases blood sugar and increases glucose consumption when stressed, while worrying more increases calorie consumption. .

Therefore, when brain cells have high energy metabolic activity due to stress, oxygen consumption is increased, and a large amount of free radicals are generated. Due to the free radicals generated in this way, free radical defense mechanisms in vivo do not function properly. Is leaked from this defense system and binds to various substances in the cells, such as proteins, nucleic acids, lipids, and the like, causing cell metabolism damage or cell destruction [Cross, EC, et al, Annals. Intem. Med., 197, p. 526-545 (1987). In particular, the biofilm lipid peroxidation process, which acts directly on the biofilm, is the first harmful action of free radicals. The microsomal membrane present in the cell membrane or mitochondria and endoplasmic reticulum contains a large amount of polyunsaturated fatty acids with many double bonds, oxygen molecules are better dissolved in the lipid layer than the water layer, and iron complexes and ham proteins, which are powerful oxidation promoters, exist around the biofilm. Because of the active oxygen, membrane components of biological membranes are attacked, denatured, and spatial arrangement is changed, which is why it is easy to lose physiological activity of biological membranes [Ekstrom and lngelman- Sundberg. Eur. J. Biochem., 158, p. 195-201 (1986)].

In view of this mechanism of action, the brain has a large amount of energy demand, which is an important organ for the continuous supply of oxygen, and the organ that is larger than any tissue for damage caused by free radicals. Therefore, metabolic activity caused by heavy rain and stress increases radical production, and oxygen demand increases, causing changes in endothelial cells and blood-barrier caused by large amounts of free radicals generated in this process. It varies the permeability, and resulting in an abnormality in calcium metabolism cell and increases the influx of calcium ions into a cell, phospholipid and Pace a to ₂ enable (phospholiphase a ₂₎ results in a more than brain membranes by participating in arachidonic acid metabolism Prostaglandin-based substances, which are pain-causing substances liberated by tissue damage, accumulate excessively and are involved in cerebrovascular contraction and relaxation, causing headaches and promoting the release of other neurotransmitters, such as serotonin and bradykinin. Binding to these pain receptors is also thought to cause headaches.

However, it is experimentally known that the injection of prostaglandin E ₂ produced by cyclooxygenase from the arachidonic phase causes pain and headache at the injection site while the headache-inducing substance is not yet known [Ryan RE et al. Headache and head pain; diagnosis and treatment. The CV Mosby Company. 91-95 (1978), Norman, AW et al. Hormones. Academinc press. 661-171 (1987). Therefore, this prostaglandin E ₂ is regarded as one of the headache causing substances.

Migraine has been shown to work directly with serotonin, one of the brain neurotransmitters. In severe cases, ergotamine, a serotonin inhibitor, has to be taken. [Reference: Peroutka, S.J. et al., Headache; the journal of head and face pain, 33 (7), 347-50 (1993), Lance J.W., Neurology, 43 (6 Suppl 3) p. S11-15 (1993)]. Most anti-inflammatory drugs currently on the market are inherently effective in general pain, such as muscle pain and neuralgia. The mechanism of action is mainly due to the inhibition of cyclooxygenase, an enzyme that converts arachidonic acid to prostaglandin during pain-induced mechanisms. It is known to prevent them, and they are generally found to be effective in headaches, and thus are widely used as a headache treatment.

However, all of them have serious side effects. They cannot be used for patients with hypertension, organic heart disease, liver disease, glaucoma, etc., and are recommended to be carefully administered to peripheral vascular disorders. In addition, temporary administration may cause skin rash, nausea, vomiting and respiratory distress depending on the constitution, and overdose may cause liver failure, kidney failure and necrosis of myocardium. And prolonged administration due to serious side effects such as gastric perforation (Roger, M., Pharmaceutical Newsletter, 3 (2), 1-6 (1992)).

Accordingly, the present inventors have studied to develop a new headache treatment agent that exhibits excellent pain relief effect without various side effects, which are problems of the conventional headache treatment agent, and as a result, vitamin E serves as an antioxidant to remove free radicals in the body. Based on the idea that the headache can be fundamentally cured by blocking the headache-inducing mechanism of, the experiment was repeatedly performed on a composition containing vitamin E and various other ingredients.

Vitamin E is a fat-soluble vitamin that is effective in preventing cancer, preventing aging, preventing heart and circulatory diseases, and preventing adult diseases such as cataracts and diabetes mellitus. Except, no toxicity has yet been reported.

Vitamin C is known to be involved in muscle activity, control of cholesterol metabolism, detoxification of harmful substances, increased resistance to infections and brain function [Kim, Gil-Soon, Pharmacist, June 14, 1993]. Vitamin C plays an important role in fatigue recovery because it is carnitine (also known as vitamin B _T ) in the body and is involved in the supply of energy necessary for muscle contraction. [Reference: Shim Gil-Soon, Pharmacist, June, 1993] / 14], and experiments with guinea defendants, rodents that do not synthesize vitamin C like humans, has shown that the addition of vitamin C prevents lipid peroxidation [Ref .: Chen, J et al., J. Ntr., 108, 1616-1620 (1978). Vitamin C is absorbed according to the degree of administration, and since it is water-soluble, it is easily excreted by the kidneys, so there are few side effects due to accumulation [Reference: Shim Gil-Soon, Pharmacist, 1993. 6/14].

Vitamin E and vitamin C obtained by natural extracts, fermentation or synthesis have been reported various physiological activities as described above, it is not known until now to prevent and treat headache as in the present invention.

The inventors have determined that the main cause of headaches and migraine headaches due to heavy stress is due to the harmful action of free radicals produced in vivo and provided that vitamin E alone or vitamin C can be treated by removing these harmful free radicals. By administering with a mixture with vitamin B and / or methionine, it was confirmed that there is an excellent effect on tension headache, migraine headaches and completed the present invention.

Accordingly, the present invention relates to a composition for the prevention and treatment of tension headaches, characterized by containing vitamin E.

The present invention also relates to a composition for the prevention and treatment of tension headaches and migraines further comprising one or more components selected from the group consisting of vitamin E and optionally preferably vitamin C and vitamin B, methionine and also particularly preferably methionine. It is about.

Vitamin E, vitamin C and methionine which can be used in the composition of the present invention can be any natural or synthetic products, but in the case of vitamin E, it is preferable to use natural because of its excellent absorption and accumulation rate in the body.

The vitamin B complex used in the present invention is a mixture of vitamin B groups such as thiamine (vitamin B ₁ ), riboflavin (vitamin B ₂ ), pyridoxine (vitamin B ₆ ), cyanocobalamin (B ₁₂ ), nicotinamide, and pantothenic acid. Again, either natural or synthetic products may be used.

The effective dose for the prevention and treatment of the headache of vitamin E used in the compositions of the present invention depends on the intensity of pain, the purpose of administration, ie whether it is for treatment or preventive purposes, and is generally 0.5 IU per kg of adult weight per day 0.38 mg) to 20 IU (13.5 mg), preferably 4.5 IU (3 mg) to 10.5 IU (7 mg).

The composition according to the present invention shows a synergic effect in the treatment and prevention of headache when vitamin C is used in combination with vitamin E alone, and almost no headache when vitamin B group or methionine is added. It showed a particularly excellent effect of 100% inhibition or prevention.

The present invention is therefore characterized in that it contains a composition containing vitamin E useful as an agent for the treatment and prevention of headache, preferably vitamin E and one or more components and methionine selected from the group consisting of vitamin C and vitamin B further. Provided are compositions for the prevention and treatment of headaches.

In the composition of the present invention, when vitamin E is used in combination with vitamin C, vitamin B and methionine, their mixing ratio is generally 1-40: 1-40: 1-10; 1-40 by weight. In particular, the ratio is preferably 2-20: 2-20: 1-5: 2-20.

The composition according to the present invention can be prepared in accordance with conventional methods in the pharmaceutical field by adding conventional pharmaceutical carriers suitable for oral administration as necessary, for example, excipients, diluents, stabilizers, emulsifiers, artificial flavors, sweeteners, pigments and the like. Formulations for oral administration may be formulated in the form of powders, tablets, hard or soft capsules, solutions, and the like.

The composition according to the present invention may further contain amino acids, antioxidants, sugars, organic acids, medicinal plants, or fruit juices, etc., if necessary, and salts, soups, grains, fish, Seaweed or other foods may also be added.

The composition according to the invention comprises once to six times daily dosages of the formulations defined above, or a unit dose containing 1/2, 1/3, 1/4, 1/5 or 1/6 thereof. It can be taken before or after meals, especially after taking into account the absorption of fat-soluble vitamins.

The invention is illustrated in more detail by the following examples, which, however, do not limit the invention.

Example 1 (tablet: 1,000 tablets)

Component Content (Increase)

Vitamin E … … … … … … … … … … … … … … … … … … … … … … 400,000 I.U.

Lecithin… … … … … … … … … … … … … … … … … … … … … … … … … … … … 6.0 g

Lactose… … … … … … … … … … … … … … … … … … … … … … … … … … … … 8.0g

Hard silicic anhydride. … … … … … … … … … … … … … … … … … … … … … … … 1.0 g

Magnesium stearate … … … … … … … … … … … … … … … … … … … … 4.0g

Carboxymethylcellulose… … … … … … … … … … … … … … … … … … … … … 3.0 g

Polyvinylpyrrolidone… … … … … … … … … … … … … … … … … … … … … … … 2.0 g

Combining the above components are prepared by tableting 1,000 tablets according to a conventional tablet production method.

Example 2 (soft capsule: 1,000 capsules)

Component Content (Increase)

Vitamin E… … … … … … … … … … … … … … … … … … … … … … … 400,000 I.U.

Vitamin C… … … … … … … … … … … … … … … … … … … … … … … … … 500.0 g

Methionine… … … … … … … … … … … … … … … … … … … … … … … … … 200.0 g

Lecithin… … … … … … … … … … … … … … … … … … … … … … … … … … 25.0 g

Beeswax… … … … … … … … … … … … … … … … … … … … … … … … … … … 50.0 g

Palm oil… … … … … … … … … … … … … … … … … … … … … … … … … … 100.0 g

Soybean oil… … … … … … … … … … … … … … … … … … … … … … … … … 100.0 g

After combining the above components in a specified amount, 1,000 soft capsules are prepared according to a conventional soft capsule preparation method.

Example 3 (Tablet: 1,000 capsules)

Component Content (Increase)

Vitamin E… … … … … … … … … … … … … … … … … … … … … … … 200,000 I.U.

Vitamin C… … … … … … … … … … … … … … … … … … … … … … … … … 500.0 g

Thiamine hydrochloride… … … … … … … … … … … … … … … … … … … … … … … … … 6.0 g

Riboflavin… … … … … … … … … … … … … … … … … … … … … … … … … 6.0 g

Cyanocobalabin… … … … … … … … … … … … … … … … … … … … … … … 0.1g

Lecithin… … … … … … … … … … … … … … … … … … … … … … … … … … 25.0 g

Lactose… … … … … … … … … … … … … … … … … … … … … … … … … … 16.0 g

Hard silicic anhydride. … … … … … … … … … … … … … … … … … … … … … … … 1.0 g

Magnesium stearate … … … … … … … … … … … … … … … … … … … 6.0 g

Carboxymethylcellulose… … … … … … … … … … … … … … … … … … … … 5.0 g

Polyvinylpyrrolidone… … … … … … … … … … … … … … … … … … … … … … 5.0 g

By combining the above components, 1,000 tablets are prepared according to a conventional tablet production method.

Example 4 (liquid)

Component Content (Increase)

Vitamin E… … … … … … … … … … … … … … … … … … … … … … … 200,000 I.U.

Vitamin C… … … … … … … … … … … … … … … … … … … … … … … … … 200.0 g

Methionine… … … … … … … … … … … … … … … … … … … … … … … … … 100.0 g

Riboflavin… … … … … … … … … … … … … … … … … … … … … … … … … 5.0 g

Lecithin… … … … … … … … … … … … … … … … … … … … … … … … … … 10.0 g

Sorbitol… … … … … … … … … … … … … … … … … … … … … … … … … … … 1.0 g

Hydroxypropylcellulose ... … … … … … … … … … … … … … … … … 50.0 g

Sorbic acid… … … … … … … … … … … … … … … … … … … … … … … … … … 10.0 g

Butylhydroxytoluene… … … … … … … … … … … … … … … … … … … … 4.0g

Butylhydroxyanisole… … … … … … … … … … … … … … … … … … … … 2.0 g

Menthol… … … … … … … … … … … … … … … … … … … … … … … … … … … … Quantity

Purified water … … … … … … … … … … … … … … … … … … … … The total volume is 10 liters.

In accordance with a conventional liquid preparation method, the above components are mixed and stirred to prepare a desired liquid preparation.

Experiment 1: Headache Test of Public

In this experiment, 200 questionnaire surveys were conducted twice, one month apart, and once more while taking vitamins. The study found that 12 people (6%) had headaches almost daily, 64 (32%) once or twice a week, 20 (10%) once or twice a month, and headaches. People (52%). Of these, 14 (7%) had migraine headaches more than once a week. Of the three surveys, 70 people who had headaches more than once or twice a week were always selected.

Vitamins used in the experiment were used by Roche, Switzerland and commercially available.

The experimental group in the present invention was tested by administering a sample of the following dose divided as described in Table 1.

TABLE 1 Content of each component in the composition used in the experimental group

* Ingredient is mg / 60kg / day, except vitamin E is I.U.

The vitamin B complex is a mixture of 6 mg thiamine hydrochloride, 6 mg riboflavin, 1 mg pyridoxine hydrochloride, 1 mg cyanocobalamin, 22.98 mg nacotinamide, and 5 mg calcium pantothenate.

The samples were filled in capsules and taken daily after lunch for 2 months, respectively, and then the degree of improvement of headache and migraine was examined in a questionnaire format.

The headache evaluation method in this experiment is as follows.

Headaches generally begin at a fairly rapid rate of pain, reach a peak at a fairly rapid rate, as shown in the accompanying FIG. 1, and then gradually sink into a sedation state over time.

Headache evaluation in this experiment was to grasp the model of the chart of Figure 1 as the area concept, and the degree of headache in each subject was expressed as a percentage of the total area under the curve of the chart.

The results are shown in Table 2 below.

[Table 2] Improvement of headache (%)

As a result of this, vitamin E alone improved the headache in normal people. Therefore, if vitamin C and vitamin B or methionine is mixed and administered, the synergistic headache is higher than vitamin E alone or vitamin E alone. The improvement effect was shown.

Experiment 2: Headache Improvement Effect in Shooting Athletes

Shooters are tense practice almost every day, and over 70% of athletes have their usual headaches. Therefore, we studied 35 people who had tension headache symptoms more than once a week among shooting athletes who had the same food and living conditions as they lived in the dormitory. Six athletes who feel double migraine are included.

Kinds and dosages of the experimental drugs according to each experimental group were taken as the control group in the Experiment 1, A 3, B 2, C 1 and C 2 conditions, after lunch for one month and three days the most fatty meal. Three days before the match, he was taking vitamins for one month, with five practice sessions and one record day.

And free fatty acids in serum 1 month before, 3 days before, and 20 minutes after shooting [Ref. Smith, S.W., Anal. Biochem., 67,531-539 (1975)] and lipid peroxides (see Yagi, K., Lipid Peroxides in Bioligy and Medicine (1980), Academic press, p. 230-240). Lipid peroxide was measured by correcting the error because the error is too large, about 30% or more by the conventional Yagi method. That is, thiobarbituric acid (thiobarbituric acid) was added and the reaction tube was filled with nitrogen gas before the reaction for 1 hour at 95 ℃ to remove oxygen and the lid was reacted. By measuring in this way, the error could be greatly reduced (p0.009, ie statistically significant ANOVA test). Lipid peroxide content was calculated using oleic acid as a standard. The measurement results are shown in FIGS. 1 and 2.

Taking 3 months of vitamins for 3 months before the game, the usual and 5 days of practice shots and 1 day of recorded shots during the week and the degree to improve the headache after the test shots were evaluated based on the same criteria as in Experiment 1. 4 is shown.

[Table 3] Improvement of headache in practice shooting and shooting shot of shooting athletes (%)

[Table 4] The degree to which shooting athletes feel headache after shooting

As described above, the usual headaches of practice shooting and recording shooting showed excellent improvement effects when vitamin E alone was administered, vitamin C and vitamin B in combination, and methionine added thereto. .

In addition, regarding the headache felt after the match shooting in Table 4, it was confirmed that the pain was significantly reduced when taking the composition according to the present invention as a value compared with the intensity felt after other matches.

According to FIG. 2, the free fatty acid showed low values before and after the administration (■) and 1 month after the administration (■), but after 1 month and 3 days, the measured values (□) All showed about 18% increase over normal. This shows that these players were all very nervous in the shooting.

According to FIG. 3, the amount of lipid peroxide before and after the administration of vitamins (■) and 1 month after administration (■) was almost the same, but serum peroxide after serum (□) was the highest in the control group. Vitamin C + vitamin B + methionine (C2) vitamin E + vitamin C + vitamin B (B2) vitamin E + vitamin C + vitamin B + methionine (C1) vitamin E (A3).

Therefore, the proportional relationship between the degree of headache and the amount of lipid peroxide in Table 4 is established, which is consistent with the hypothesis of the present inventors' headache mechanism.

On the other hand, the composition according to the present invention was confirmed to have an excellent headache relief effect.

Experiment 3: Change of secretion of headache-inducing substance after shooting competition of shooting athlete

The following experiments were conducted to see the changes in the contents of prostaglandin E ₂ and serotonin, which are thought to be the headache contingencies after shooting.

The type and dosage of the experimental drug according to each experimental group was the A3 condition of vitamin E administration to the headless, headache and headache patients in Experiment 1, after lunch having the most fatty meal in the dormitory for 2 weeks. It was taken.

Serotonin is too fast to metabolize and is difficult to measure in serum, so 5-HIAA (5-hydroxyindoleacetic acid), a stable metabolite, is usually measured using urine. [Reference: Olesen, J. et al., Basic mechanisms of headache . Elsevier Science Publishers BV, 463-477 (1988). Prostaglandin E _2, known as a pain-causing substance, is estimated to have a short half-life, but there is no stable metabolite produced only from this substance. However, it was measured using Amersham's Prostaglandin E ₂ measurement kit.

Therefore, 20 minutes after the end of the match, the most severe headache, so blood was collected and serum serum was isolated to measure prostaglandin E ₂ . 5-HIAA, a metabolite of serotonin, was measured by Curzon method after receiving urine 40 minutes after firing competition [Curzin, G et al, Br.J. Phannacol. 43.39-52 (1971).

The results are in Table 5.

[Table 5] Prostaglandin E ₂ , 5-HIAA Change after Shooting

Headache and headache in prostaglandin E ₂ : Significant difference in p0.05, Headache and A3: Significant difference in p0.01, Headache and A3: Significant difference in p0.01, No in 5-HIAA Headache and headache: Significant difference between p0.01, Headache and A3: Significant difference between p0.05, Headache and A3: Significant difference between p0.01.

In Table 5, prostaglandin E _{2 has} a significant difference in the case of headache and headache, but vitamin E (A3) administration is not significantly different from any one, but has a value close to a headache. And if you have headaches, taking vitamin E is a good way to reduce the production of prostaglandin E ₂ .

On the other hand, 5-HIAA, a metabolite of serotonin, was found to be significantly different in the case of headache and headache, and in the case of headache and vitamin E users. Therefore, taking vitamin E significantly inhibits the production of sirotonin and decreases prostaglandin E ₂ production.

As a result, taking vitamin E led to the disappearance of headaches in daily practice sessions with relatively low stress levels and once-weekly shots, and too high stress levels in competition shots, resulting in slightly more prostaglandin E ₂ or serotonin than needed. Seems to be.

The proportional relationship between the headache degree in Table 5 and the contents of prostaglandin E ₂ and 5-HIAA is established, which is consistent with the hypothesis of the present inventors' headache mechanism.

Experiment 4: Effect on Chronic Headache

Chronic headache is almost always a type of tension headache. Sixty patients with chronic headache were tested. These were divided by the experimental group in the same treatment method as in Experiment 1 to administer the experimental drug and the results are shown in Table 6 below.

[Table 6] Improvement of Headache in Chronic Headache Patients

From the above results, it can be confirmed that the composition according to the present invention remarkably reduces headaches and migraines even in chronic headache patients.

Experiment 5: Writing Experiment of Mouse

The most commonly used method for screening analgesic substances is ac-tic aicd-induced writhing test method [Niemegeers, et al. Drug-Res. 1505 (1975). After 30 minutes of subcutaneous administration, 1.0% acetic acid is injected into the abdominal cavity at a rate of 0.1ml / 10g per body weight to show writhing, which extends the hind feet.Writhing is measured 10 minutes after drug administration. .

20 males of 25-25 g of these experimental ICR mice were used in each group. Drug administration was fed by way of addition to the synthetic diet. Butyl hydroxytoluene (BHT), the most famous chemical compound, is added to the diet so that 0.01% and vitamin E is 0.1%. Other ingredients are from Sigma and ICN Biomedicals, Inc. The composition of the synthetic diet was referred to Stanley paper [Stanley, S et al. J. Nutr 114, 1924-1933 (1984). Synthetic ingredients include casein vitamin free 20%, corn starch 20%, sugar 45%, cellulose 5%, choline chloride 0.2%, and DL-methionine 0.07 %, Lard 5%, vitamin mixture (vitamin B ₁₂ , D ₃ , K ₃ 0.2, 0.582, 0.6, a-tocopherol acetate 1.33, retinol aceteate 93.2, thiamin-HCI 59.0, pyriodxine-HCI 29.0 , D-bioton 1.0, folic acid 2.0, Ca-pantothenate 235.0, riboflavin 59.0, nicotinic acid 294.0 mg / 100g) 1.0%, mineral mixture (CaCO ₃ 29.29, CaHPO ₄ 2H ₂ O 0.43, KH ₂ PO ₄ 34.31, NaCL 25.06, MgSO ₄ 7H ₂ O 9.98, Fe (C ₆ H ₅ O ₇ 6H ₂ O 0.623, CuSO ₄ 5H ₂ O 0.156, MnSO ₄ H ₂ O 0.121, (NH ₄ ) ₆ MO ₇ O ₂₄ 0.0025 , Na ₂ SeO ₃ .5H ₂ O 0.0015, Zncl ₂ 0.02, KI 0.0005) 3.5%.

The results are shown in Table 7.

Table 7 Lighting Experiments

Vitamin E and vitamin C are already known to be ineffective in lighting experiments. This is because the type of lighting test does not absorb vitamins completely into cells within 30 minutes after vitamin administration.

However, when the long-term administration of the composition of the feed added to the formula can be clearly seen in the analgesic effect shown in Table 6 above, it can be seen that the antioxidant effect of vitamin E will stop the pain. This is because BHT, a potent antagonist, has an analgesic effect in lighting experiments with acetic acid.

Claims (9)

A composition for preventing and treating tension line headaches and migraines, comprising vitamin E. The composition of claim 1, further comprising one or more components selected from the group consisting of vitamin C and vitamin B. The composition of claim 1, further comprising methionine. The composition of claim 1, wherein the vitamin E is formulated to administer 0.5 I.U.E to 20 I.U. per kg body weight per adult. The composition of claim 1 containing vitamin E, vitamin C, vitamin B and methionine. 6. The composition of claim 5, which contains vitamin E, vitamin C, vitamin B and methionine in a ratio of 1-40: 1-40: 1-10: 1-40 by weight. The composition of claim 6, which contains vitamin E, vitamin C, vitamin B and methionine in a ratio of 2-10: 2-10: 1-5: 2-20 by weight. 8. A composition according to any one of claims 1 to 7, further containing at least one pharmaceutically acceptable carrier. 9. A composition according to claim 8, formulated in tablets, soft capsules or solutions.