JP2014237715A - Agent for alleviating alcoholic fatigue - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an agent for effectively alleviating symptoms of fatigue caused by alcohol intake of a healthy person, i.e. alcoholic fatigue.SOLUTION: Alcohol drinking is a widely accepted custom for living a fulfilling life such as stress release and communication improvement, however, alcohol drinking frequently causes fatigue such as next-day weariness. Thus, there is provided the alcoholic fatigue alleviating agent to safely and effectively alleviate and improve fatigue caused by alcohol intake, i.e. alcoholic fatigue by using ornithine or its salt, or using ornithine or its salt in combination with one or more components selected from the group consisting of turmeric, fermented turmeric extract and curcumin. The alcoholic fatigue alleviating agent can be administered before or after drinking the alcohol or administered by continuous administration.

Description

  The present invention improves alcoholic fatigue containing ornithine or a salt thereof, or ornithine or a salt thereof, and one or more components selected from the group consisting of turmeric, fermented turmeric extract, and curcumin as active ingredients. It is related with the alcoholic fatigue improving agent for doing.

Fatigue that humans feel in their daily lives is recognized as various symptoms such as symptoms related to drowsiness and dullness, difficulty in concentrating attention, and symptoms of physical discomfort, and subjective symptoms of fatigue. The Fatigue includes physiological fatigue and pathological fatigue. Physiological fatigue refers to a state in which physical, mental, or both functions have been reduced, and is defined as a protective response to maintain health. Specifically, it refers to fatigue that appears in daily activities such as work, housework, and leisure sports. Pathological fatigue includes heart disease, bronchial asthma, hepatitis, anemia, metabolic diseases, muscle diseases, various infectious diseases, fatigue that appears as symptoms associated with basic diseases such as cancer, chronic fatigue syndrome, mental It refers to fatigue due to depression due to causes, overtraining syndrome due to sports, etc., and is defined as fatigue feelings and subjective symptoms of fatigue resulting from various diseases and disorders.
In addition, fatigue is caused by alcohol consumption. Alcohol consumption is a widely accepted habit of living a fulfilling life such as stress relief and improved communication. However, alcohol consumption often leads to fatigue such as fatigue the next day. Alcohol is detoxified by intracellular enzymes in the liver after ingestion, but it causes various symptoms during the detoxification process or from the effects of metabolites such as acetaldehyde accumulated during detoxification. A feeling of coming fatigue, that is, fatigue caused by alcohol consumption (hereinafter, defined as “alcoholic fatigue”) is caused.

Conventionally, various nutritional agents and stress-improving agents have been taken as coping therapy for such alcoholic fatigue, but the symptoms are directly improved against fatigue caused by alcohol consumption. There are no effective improvers provided.
On the other hand, ornithine is known as a substance having various physiology and pharmacological functions and having an action for improving human physiological functions and disorders. Ornithine is used mainly in the United States and Japan as a food material that secretes growth hormone and enhances muscle synthesis, or increases basal metabolism and prevents obesity. Ornithine is used in the form of L-ornithine L-aspartate in Europe as a pharmaceutical agent for improving liver damage. Various symptom improving agents are disclosed based on the pharmacological function of ornithine. For example, in morbid fatigue associated with an increase in blood ammonia level, administration of ornithine or a salt thereof reduces blood ammonia level, and an improving agent for recovering from morbid fatigue is disclosed. (Japanese Patent Publication No. 41-8592, Japanese Patent Publication No. 42-7767, Japanese Patent Publication No. 46-3194, Arzneim.-Forsch. (Drug Res.), 1970, vol8, p1064-1067).

  International publication numbers WO2007 / 040244 and WO2007 / 142286 also deal with physical and mental fatigue that appears in daily activities such as work, housework and leisure sports, that is, physiological fatigue. As a composition for improving subjective symptoms of fatigue, or for improving symptoms of symptoms associated with various infectious diseases, underlying diseases, or pathological fatigue that appears as symptoms associated with physical or mental disorders In addition, a composition for improving a subjective fatigue symptom or an agent for reducing fatigue comprising ornithine or a salt thereof as an active ingredient is disclosed.

  Further, as other improving agents for ornithine, JP-A-2006-342148 discloses an oral preparation for improving bedtime or waking that uses ornithine or a salt thereof as an active ingredient, and JP-A-2007-31375 discloses ornithine or An oral preparation for improving skin quality containing the salt as an active ingredient is disclosed in JP 2007-119348 A, or cold remedy improving agent containing ornithine or a salt thereof as an active ingredient, and ornithine disclosed in JP 2008-50352 A. , Lysine, arginine, and a sleep improving agent containing a basic amino acid selected from citrulline, International Publication No. WO2007 / 049628 discloses a blood fluidity improving agent containing ornithine or a salt thereof as an active ingredient, respectively. Yes.

  As described above, various improving agents have been disclosed from various pharmacological functions of ornithine, but fatigue caused by alcohol intake of healthy people, that is, alcoholic fatigue is improved by ornithine or a salt thereof. unknown.

Japanese Patent Publication No.41-8592 Japanese Patent Publication No.42-7767 Japanese Patent Publication No.46-3194 JP 2006-342148 A JP 2007-31375 A JP 2007-119348 A JP 2008-50352 A International Publication Number WO2007 / 040244 International Publication Number WO2007 / 049628 International Publication Number WO2007 / 142286

Arzneim.-Forsch. (Drug Res.), 1970, vol8, p1064-1067

  The subject of this invention is providing the improvement agent which improves the symptom effectively with respect to the fatigue which arises by alcohol intake of a healthy person, ie, alcoholic fatigue.

  Fatigue that humans feel in daily life is aggregated as various symptoms such as symptoms related to drowsiness and dullness, symptoms related to difficulty in focusing attention, and symptoms of physical discomfort, and subjective symptoms of fatigue It is recognized as a common subjective symptom. However, various factors are involved in the cause of the fatigue, and improvement corresponding to the factors is required for the recovery from the fatigue. The present inventor has found that ornithine has an effective action for improving alcoholic fatigue in earnest research on improving alcoholic fatigue, and further, ornithine or a salt thereof, turmeric, fermented turmeric extract, and The inventors have found that a substance containing one or more components selected from the group consisting of curcumin has an effective action for improving alcoholic fatigue and has completed the present invention.

  That is, this invention consists of an alcoholic fatigue improving agent which contains ornithine or its salt as an active ingredient. Furthermore, the present invention comprises an alcoholic fatigue improving agent containing the ornithine or a salt thereof and one or more components selected from the group consisting of turmeric, fermented turmeric extract, and curcumin as active ingredients. The alcoholic fatigue ameliorating agent of the present invention can be administered before or after alcohol intake, and can be administered in the form of continuous administration. The alcoholic fatigue ameliorating agent of the present invention is not particularly limited, but it is desirable to administer it in the form of oral administration.

The present invention also provides ornithine or a salt thereof, or ornithine or a salt thereof, and one or more selected from the group consisting of turmeric, fermented turmeric extract, and curcumin for the production of an alcoholic fatigue ameliorating agent. Includes the use of ingredients.
Specifically, the present invention includes (1) an alcoholic fatigue improving agent containing ornithine or a salt thereof as an active ingredient, and (2) a group consisting of ornithine or a salt thereof, turmeric, fermented turmeric extract, and curcumin. The alcoholic fatigue ameliorating agent according to (1) or (3) the alcoholic fatigue ameliorating agent containing one or two or more components selected from as an active ingredient is administered before or after alcohol intake. The alcoholic fatigue ameliorating agent as described in (1) or (2) above, or (4) the alcoholic fatigue ameliorating agent characterized in that it is for continuous administration (1) to (4) above, wherein the alcoholic fatigue improving agent according to (1) or (2) or (5) the alcoholic fatigue improving agent is formulated in a form for oral administration. Alcohol fatigue according to any of One or more selected from the group consisting of ornithine or a salt thereof, ornithine or a salt thereof, turmeric, fermented turmeric extract, and curcumin for the production of an improving agent or (6) an alcoholic fatigue improving agent Use of ingredients.

  The present invention provides a safe and effective alcoholic fatigue ameliorating agent that effectively ameliorates the symptoms of fatigue caused by alcohol intake by healthy individuals, that is, alcoholic fatigue.

It is a figure which shows the reply result of the OSA sleep survey form MA version of the day following alcohol intake by the presence or absence of ornithine (ornithine hydrochloride) in the test about the ornithine alcoholic fatigue improvement effect in the Example of this invention. The white bar graph represents the placebo group, and the black bar graph represents the ornithine hydrochloride group. The vertical axis represents the standardized score, and improvement is evaluated by the height of the score (showing a high value means improvement). ** represents a significant difference from the placebo group at a risk rate of less than 1%. FIG. 2 is a diagram showing individual fluctuations in the item of fatigue recovery of FIG. 1 in a test on the effect of ornithine on alcoholic fatigue improvement in Examples of the present invention. Standardized scores are shown in Fig. 1. It is a figure which shows the answer result of the OSA sleep survey form MA version on the day after alcohol intake by the presence or absence of ornithine (ornithine aspartate) in the test about the alcoholic fatigue improvement effect of ornithine in the Example of this invention. The white bar graph represents the placebo intake group, the black bar graph represents the ornithine aspartate 800 mg (400 mg ornithine) intake group, and the hatched bar graph represents the ornithine aspartate 1600 mg (ornithine 800 mg) intake group. The vertical axis represents the standardized score, and improvement is evaluated by the height of the score (showing a high value means improvement). * Indicates a significant difference from the placebo group at a risk rate of less than 5%. In the test about the alcoholic fatigue improvement effect of ornithine in the examples of the present invention, the answer results of the VAS (visual analog scale) questionnaire test on sleep and fatigue the day after alcohol consumption depending on the presence or absence of ornithine (ornithine aspartate) are shown. FIG. The white bar graph represents the placebo intake group, the black bar graph represents the ornithine aspartate 800 mg (400 mg ornithine) intake group, and the hatched bar graph represents the ornithine aspartate 1600 mg (ornithine 800 mg) intake group. The vertical axis represents the VAS answer value, and the subject's experience is evaluated at that height (a lower value means closer to the best experience). * And ** indicate that there is a significant difference from the placebo group at a risk rate of less than 5% and a risk rate of less than 1%, respectively. It is a figure which shows the exercise | movement amount reduction inhibitory effect (alcoholic fatigue inhibitory effect) on the day following alcohol administration by the intake of ornithine (ornithine hydrochloride) in the test about the ornithine alcoholic fatigue improvement effect in the Example of this invention. Group I, Group II, and Group III represent a control group, an ethanol administration group, and an ornithine diet + ethanol administration group, respectively. The vertical axis shows swimming time. * Indicates that there is a significant difference from group II at a risk rate of less than 5%. In the test of alcoholic fatigue improvement effect by the combination of ornithine and curcumin in the examples of the present invention, the next day of alcohol consumption by ingestion of ornithine (ornithine aspartate, ORAS) and curcumin, or ingestion of curcumin alone, or placebo It is a figure which shows the answer result of the VAS (visual analog scale) questionnaire test regarding sleep and fatigue. The white bar graph represents the placebo intake group, the black bar graph represents the curcumin 30 mg intake group, and the hatched bar graph represents the ornithine aspartate 800 mg (ornithine 400 mg) and curcumin 30 mg combined use group. The vertical axis represents the VAS answer value, and the subject's experience is evaluated at that height (a lower value means closer to the best experience). * Indicates that there is a significant difference from the placebo group at a risk rate of less than 5%.

  The present invention comprises an alcoholic fatigue improving agent containing ornithine or a salt thereof as an active ingredient. Examples of ornithine used in the present invention include L-ornithine and D-ornithine. Ornithine can be obtained by a method of chemically synthesizing, a method of fermentative production, a method of extracting from a raw material, or the like. Ornithine can also be obtained by purchasing a commercial product.

Examples of a method for chemically synthesizing L-ornithine include the method described in Coll.Czechoslov.Chem.Commun., 24, 1993 (1959). Examples of the method for fermentative production of L-ornithine include the methods described in JP-A-53-24096 and JP-A-61-119194. L-ornithine and D-ornithine can also be purchased from Sigma-Aldrich.
Examples of ornithine salts include acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts, and the like. In addition, as a form other than the salt, all substances containing ornithine such as peptides and material extracts can be used.
Acid addition salts include inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, acetate, maleate, fumarate, citrate, malate, lactate, α-ketoglutarate And organic acid salts such as gluconate and caprylate.

Examples of the metal salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt and zinc salt.
Examples of ammonium salts include salts such as ammonium and tetramethylammonium.
Examples of the organic amine addition salt include salts of morpholine, piperidine and the like.

Examples of amino acid addition salts include salts of glycine, phenylalanine, lysine, aspartic acid, glutamic acid and the like. Of the above ornithine salts, hydrochloride, citrate, malate, α-ketoglutarate and aspartate are preferably used, but other salts or two or more salts may be used in appropriate combination. Good.
The present invention also comprises an alcoholic fatigue improving agent containing, as active ingredients, ornithine or a salt thereof and one or more components selected from the group consisting of turmeric, fermented turmeric extract, and curcumin. Turmeric is a ginger family plant and its scientific name is Curcuma longa L. The turmeric is a perennial and is also cultivated in tropical regions such as India, Southeast Asia, and southern China, and in the Okinawa region in Japan, and is easily available from these regions. Fermented turmeric is obtained by fermenting turmeric as a fermentation raw material. For example, after drying turmeric rhizomes or the like, the turmeric is cultivated as it is or crushed using a crusher or the like, lactic acid bacteria, yeast, hay It can be obtained by subjecting it to a fermentation treatment with microorganisms such as bacteria (Japanese Patent No. 2949411, Japanese Patent Application Laid-Open No. 2004-345986, Japanese Patent Application Laid-Open No. 2002-65199). In the present invention, turmeric prepared by these various methods or fermented turmeric can be used.

  Curcumin is a poorly water-soluble substance contained in tropical and subtropical plants represented by turmeric (Curcuma longa L.), which is mainly a turmeric and ginger family perennial, and is made from turmeric and turmeric. It is manufactured by organic solvent extraction. In addition, a method of extracting turmeric by contacting carbon dioxide in a supercritical state (JP-A-6-9479) or treating curcumin raw material in the presence of water and α-cyclodextrin Various preparation methods are known, such as a method for producing a curcumin aqueous solution by forming a curcumin clathrate and collecting it (Japanese Patent Laid-Open No. 2006-111534). In the present invention, curcumin prepared by these various methods can be used.

  The alcoholic fatigue ameliorating agent of the present invention includes ornithine or a salt thereof, or an active ingredient comprising one or more components selected from the group consisting of ornithine or a salt thereof, turmeric, fermented turmeric extract, and curcumin. As appropriate, additives suitable for each application can be contained. Examples of the additive include amino acids such as valine, leucine, isoleucine, arginine, lysine, glutamine, alanine, serine, glycine, cysteine, and threonine.

  In addition to the active ingredient consisting of one or more ingredients selected from the group consisting of ornithine or a salt thereof, ornithine or a salt thereof, turmeric, fermented turmeric extract, and curcumin, the alcoholic fatigue improving agent of the present invention, By appropriately including other components, the composition can be made more suitable for improving alcoholic fatigue. Examples of the other components include wheat-derived components, malt, wort, hops, hop extract, fresh tea leaf extract, brown rice, hard wheat, hub tea, corn, collagen peptide, drinking deep sea water, and dried rose. Hips, black beans, black sesame seeds, citrus aloe, yuzu peel, vitamins, vitamin C, spice extract, black tea, caffeine, fructose glucose sugar, salt, citrulline, organic acids, citric acid, sodium citrate, calcium lactate, pyrroline Examples include iron acid, calcium gluconate, K chloride, Mg chloride, sugar, acidulant, skim milk powder, milk protein, milk peptide, cyclodextrin and the like. The composition for improving alcoholic fatigue of the present invention comprises ornithine or a salt thereof, or an active ingredient comprising one or more components selected from the group consisting of ornithine or a salt thereof, turmeric, fermented turmeric extract, and curcumin. It may contain one or two or more pharmacologically acceptable carriers as necessary, and may further contain other therapeutic active ingredients as necessary.

  The alcoholic fatigue improving agent of the present invention requires ornithine or a salt thereof, or an active ingredient comprising one or more components selected from the group consisting of ornithine or a salt thereof, turmeric, fermented turmeric extract, and curcumin. Accordingly, it can be mixed with a carrier and the like, and can be produced by any method well known in the technical field of pharmaceutics. The dosage form of the preparation is desirably the most effective in the treatment, and oral administration or parenteral administration such as intravenous, intraperitoneal or subcutaneous administration is preferable, but oral administration is more preferable. . Examples of dosage forms to be administered include tablets, powders, granules, pills, suspensions, emulsions, soaking / decoction, capsules, syrups, solutions, elixirs, extracts, tinctures, fluid extracts, etc. Any of parenteral preparations such as oral preparations, injection preparations, instillation preparations, cream preparations, and suppositories may be used, but they are preferably used as oral preparations.

  When formulating the alcoholic fatigue improving agent of the present invention, excipients, binders, disintegrants, lubricants, dispersants, suspending agents, emulsifiers, diluents, buffers, antioxidants, bacteria Additives such as inhibitors can be used. In the case of liquid preparations such as syrups suitable for oral administration, sugars such as water, sucrose, sorbitol and fructose, glycols such as polyethylene glycol and propylene glycol, oils such as sesame oil, olive oil and soybean oil Preservatives such as p-hydroxybenzoic acid esters, and flavors such as strawberry flavor and peppermint can be added to prepare a preparation.

  In the case of tablets, powders, granules, etc. suitable for oral administration, sugars such as lactose, sucrose, glucose, sucrose, mannitol, sorbitol, starches such as potato, wheat, corn, calcium carbonate, calcium sulfate , Inorganic substances such as sodium bicarbonate, sodium chloride, excipients such as plant powder such as licorice powder, gentian powder, starch, agar, gelatin powder, crystalline cellulose, carmellose sodium, carmellose calcium, calcium carbonate, sodium bicarbonate , Disintegrants such as sodium alginate, lubricants such as magnesium stearate, talc, hydrogenated vegetable oil, macrogol, silicone oil, polyvinyl alcohol, hydroxypropylcellulose, methylcellulose, ethylcellulose, carmellose, gelatin, starch paste, etc. Join , Surfactants such as fatty acid esters, by adding a plasticizer such as glycerin, can be formulated.

In addition, preparations suitable for oral administration include additives generally used in foods and drinks such as sweeteners, coloring agents, preservatives, thickening stabilizers, antioxidants, color formers, bleaches, fungicides, gum bases. Bitterings, enzymes, brighteners, acidulants, seasonings, emulsifiers, strengthening agents, manufacturing agents, fragrances, spice extracts and the like may be added.
Suitable formulations for oral administration are as is or for example beer, fermented alcoholic beverages, beer-taste beverages, juices, soft drinks, teas, lactic acid bacteria beverages, fermented milk, frozen desserts, butter, cheese, yogurt, processed milk, defatted Dairy products such as milk, livestock meat products such as ham, sausage, hamburger, fish paste products such as salmon, bamboo rings, and fish cakes, egg products such as broiled and egg tofu, cookies, jelly, chewing gum, candy, snacks and other confectionery Bread, noodles, pickles, salmon products, dried fish, boiled, salted products, soups, seasonings, etc., powdered foods, sheet foods, bottled foods, canned foods, retort foods, capsule foods, tablet foods, liquid foods Foods and drinks such as health foods for improving alcoholic fatigue, functional foods, dietary supplements, foods for specified health use, etc. It may be used in.

  For example, injections suitable for parenteral administration preferably comprise a sterile aqueous solution containing ornithine or a salt thereof that is isotonic with the blood of the recipient. For example, in the case of an injection, a solution for injection is prepared using a carrier such as a salt solution, a glucose solution, or a mixture of a salt solution and a glucose solution. Also in these parenteral agents, one or more selected from the diluents, preservatives, excipients, disintegrants, lubricants, binders, surfactants, plasticizers and the like exemplified in the oral agents. An auxiliary component may be added.

  The concentration of ornithine or a salt thereof in the alcoholic fatigue ameliorating agent of the present invention is appropriately selected according to the type of preparation, the effect expected by administration of the preparation, etc. 90% by weight, preferably 0.05 to 80% by weight, particularly preferably 0.1 to 70% by weight. The dose and frequency of administration of the preparation of the present invention vary depending on the dosage form, age of the person to be administered, body weight, etc., but usually 5 mg to 30 g as ornithine or a salt thereof per day for an adult, It is administered once to several times a day, preferably 50 mg to 10 g, particularly preferably 200 mg to 3 g, more preferably 400 mg to 1 g. The administration period is not particularly limited, but is usually 1 day to 1 year, preferably 1 day to 3 months.

  Alcoholic fatigue can be improved by administering or ingesting the medicament or food or drink of the present invention. In the present invention, alcoholic fatigue refers to fatigue caused by alcohol consumption. Fatigue is synonymous with fatigue. The fatigue includes physiological fatigue and pathological fatigue, and the medicament or food or drink of the present invention is preferably used for improving physiological fatigue associated with alcohol intake.

  Physiological fatigue refers to a state in which physical, mental, or both functions have declined, and is defined as a protective response to maintain health. More specifically, it refers to fatigue that appears in daily activities such as work, housework and leisure sports. Alcoholic fatigue includes all the physical and mental fatigue caused by alcohol consumption, such as reduced sleep quality caused by drinking, malaise the next day, and reduced exercise capacity.

On the other hand, pathological fatigue includes heart disease, bronchial asthma, hepatitis, anemia, metabolic disease, muscle disease, various infectious diseases, fatigue that appears as symptoms associated with basic diseases such as cancer, chronic fatigue syndrome, mental It means fatigue due to cause depression, sports overtraining syndrome, etc.
Alcoholic fatigue that can be improved by administering or ingesting the medicament or food or drink of the present invention is not particularly limited, but preferably includes symptoms related to drowsiness and dullness observed on the day after drinking, and difficulty in concentrating attention.

  Symptoms related to drowsiness and dullness include, for example, heavy head, sluggish whole body, dull legs, shortness of breath, yawning, dull head, sleepiness, tired eyes, and difficulty standing It is done. Symptoms related to difficulty in concentrating attention include, for example, a lack of thoughts, discomfort to talk, annoyance, distractions, not being enthusiastic about things, not being able to remember a few things, and many mistakes And so on.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated further more concretely, this invention is not limited to these Examples.

[Test of ornithine on alcoholic fatigue improvement (sleep and fatigue)]
<Test method>
16 healthy adult volunteers with N / D acetaldehyde dehydrogenase genotype (11 males, 5 females, ages 24 to 49 years old) were treated with 2000 mg ornithine hydrochloride (1600 mg as ornithine) or placebo ( Crystalline cellulose) was taken in two doses before and after drinking, and the OSA sleep questionnaire MA version was answered when waking up the next day. The subjects received 10 ml of beer (5% alcohol) per kg of body weight in 6 divided doses every 4 minutes. The test meal was provided in a capsule form so that it could not be judged by taste and shape, and the test was conducted by double-blind testing of two test meals.
<Result>
As a result, a significant improvement was observed in the ornithine hydrochloride intake group compared to the placebo group in terms of fatigue recovery on the OSA sleep questionnaire MA version (Figure 1). Improvements were also observed in the items of sleepiness at waking, sleep and sleep maintenance, and sleep time. In addition, improvement in fatigue recovery was confirmed in 13 of 16 (approximately 80%) (Figure 2). From the above results, it became clear that fatigue caused by drinking was improved by ornithine intake.

[Test on the effect of ornithine on alcoholic fatigue (sleep and fatigue)
<Test method>
Eleven healthy adult volunteers with N / D acetaldehyde dehydrogenase genotype (8 males, 3 females, ages 26-49 years old) with 800 mg or 1600 mg ornithine aspartate (ornithine, 400 mg, 800 mg) or placebo (crystalline cellulose) was taken after drinking, and when they woke up the next day, they answered the OSA sleep questionnaire MA version and the VAS (visual analog scale) questionnaire on sleep and fatigue. Subjects took 10 ml of beer (5% alcohol) per kg of body weight in 3 divided doses every 10 minutes. The test meal was provided in capsule form so that it could not be judged by taste and shape, and the test was conducted by cross-over double-blinding of 3 test meals.
<Result>
As a result, significant improvement was observed in the ornithine aspartate 800 mg (ornithine 400 mg) intake group compared to the placebo group in the sleep and sleep maintenance items of the OSA sleep questionnaire MA version (FIG. 3). In the same item, improvement was also observed in the group taking ornithine aspartate 1600 mg (ornithine 800 mg). Moreover, in the dream item, improvement was observed in the ornithine aspartate 800 mg (ornithine 400 mg) intake group and the ornithine aspartate 1600 mg (ornithine 800 mg) intake group.

  In the VAS questionnaire test on sleep and fatigue, significant improvements were observed in the ornithine aspartate 800 mg group in terms of fatigue and sleep status when waking up (Figure 4). Improvements were also observed in the ornithine aspartate 1600 mg intake group (Fig. 4). In all other questions, improvements were observed in the ornithine aspartate intake group (Fig. 4). These results indicate that the decrease in sleep quality caused by drinking and the fatigue of the next day were improved by ornithine intake, and the effect of ornithine on alcoholic fatigue was clarified.

[Test for the effect of ornithine on alcoholic fatigue (momentum reduction)]
<Test method>
After acclimatizing 90 ddY mice (male) 5 weeks old purchased from Japan SLC Co., Ltd. with a standard diet (AIN93G) for 1 week, they were forced to swim at a water temperature of 30 ± 1 ° C with a weight of 9% of their body weight. . Breeding conditions were from 8: 00-20: 00 during the light period and 20: 00-8: 00 during the dark period, and all swimming experiments were conducted after 15 hours of fasting. Forty individuals with the same swimming time were selected and divided into groups of 10 animals as follows so that the swimming time and weight were uniform among the groups.
Group I (control group); Group II (ethanol group); Group III (ornithine diet, ethanol group).

Groups I and II were AIN93G, and group III was AIN93G mixed with 1% ornithine (1.25% ornithine hydrochloride) for 1 week. On the night before the test, physiological saline was administered to group I, and ethanol of 4 g / kg body weight was administered to groups II and III, and fasting was started. After fasting for 15 hours, the above-mentioned forced swimming test was carried out in the morning of the next day, and the mice were allowed to swim and the swimming time until exhaustion was measured. The standard for fatigue was when the mouse's nose submerged in water for 5 seconds.
<Result>
As a result, the swimming time decreased in group II compared to group I, indicating that the swimming time decreased due to ethanol intake (Fig. 5). On the other hand, this decrease in swimming time was suppressed in group III, indicating that ornithine has the effect of suppressing the decrease in swimming time due to ethanol intake (Fig. 5). Since the decrease in swimming time indicates that the mice are fatigued, the results of this study revealed that ornithine has an effect of improving alcoholic fatigue.

[Test on the effect of ornithine and curcumin in improving alcoholic fatigue (sleep and fatigue)]
<Test method>
13 healthy adult volunteers with acetaldehyde dehydrogenase genotype N / D (10 males, 3 females, ages 25-49) with 800 mg ornithine aspartate (400 mg ornithine) and 30 Take mg mg of curcumin (turmeric pigment), 30 mg of curcumin (turmeric pigment), or placebo (crystalline cellulose) after drinking and answer the VAS (visual analog scale) questionnaire on sleep and fatigue when you wake up the next day I was asked to. Subjects took 10 ml of beer (5% alcohol) per kg of body weight in 3 divided doses every 10 minutes. The test meal was provided in capsule form so that it could not be judged by taste and shape, and the test was conducted by cross-over double-blinding of 3 test meals.
<Result>
As a result, significant improvement was observed in 3 items of awakening, waking up fatigue and dullness in getting up in the group taking ornithine and curcumin together, and improvements were observed in all other items (Fig. 6). : VSA (visual an alog scale) questionnaire on sleep and fatigue. In the group receiving curcumin alone, improvement was observed in all items, but no significant difference was observed (FIG. 6). Comparing the group taking ornithine and curcumin together with the group taking curcumin alone, the improvement effect was higher in the group taking ornithine and curcumin in 5 items except for the sleep depth item. These results indicate that taking ornithine and curcumin in combination with curcumin alone is more effective in reducing sleep quality caused by drinking and improving fatigue on the following day. And the effect of curcumin combination became clear.

The present invention provides a safe and effective alcoholic fatigue ameliorating agent that effectively ameliorates the symptoms of fatigue caused by alcohol intake by healthy individuals, that is, alcoholic fatigue.

Claims (6)

An alcoholic fatigue improving agent containing ornithine or a salt thereof as an active ingredient. 2. The alcoholic fatigue ameliorating agent according to claim 1, comprising ornithine or a salt thereof and one or more components selected from the group consisting of turmeric, fermented turmeric extract, and curcumin as active ingredients. 3. The alcoholic fatigue ameliorating agent according to claim 1 or 2, wherein the alcoholic fatigue ameliorating agent is for administration before or after alcohol consumption. 3. The alcoholic fatigue ameliorating agent according to claim 1 or 2, wherein the alcoholic fatigue ameliorating agent is for continuous administration. The alcoholic fatigue ameliorating agent according to any one of claims 1 to 4, wherein the alcoholic fatigue ameliorating agent is formulated in a form for oral administration. Use of ornithine or a salt thereof, or one or more components selected from the group consisting of ornithine or a salt thereof, turmeric, fermented turmeric extract, and curcumin for the production of an alcoholic fatigue relieving agent.