JPWO2007023931A1 - Composition for suppressing increase in blood alcohol concentration - Google Patents

Abstract

Drugs, functional foods, and the like that create a comfortable drinking state of suppressing a drought state by suppressing an increase in blood alcohol concentration after drinking and enjoying moderate intoxication are desired. That is, an object of the present invention is to provide a composition for suppressing an increase in blood alcohol concentration. ADVANTAGE OF THE INVENTION According to this invention, the composition for suppression of a blood alcohol concentration rise which contains basic amino acids, such as ornithine, arginine, a lysine, histidine, a citrulline, or its salt as an active ingredient can be provided.

Description

  The present invention relates to a composition for suppressing an increase in blood alcohol concentration, which contains a basic amino acid or a salt thereof as an active ingredient.

In a drunk state due to excessive drinking, there are many negative factors that affect society, such as social problems that accompany drinking, accidents caused by impaired consciousness, and an increase in incidents.
Conventionally, as a substance or composition that reduces or suppresses the increase in blood alcohol concentration after drinking, a mixture of persimmon vinegar (see Patent Document 1), cabbage, red purple soup, carrot and parsley juice (see Patent Document 2) ), Ethanol-insoluble matter of an aqueous solvent extract of ginseng (see Patent Document 3), glycerol (see Patent Document 4), a composition containing a tea extract and a porphyrin pigment (see Patent Document 5), a pepino extract ( Patent Document 6) is known.

On the other hand, in an acute alcohol intoxication model, the survival rate is increased by single administration of amino acids such as alanine, threonine, leucine, and isoleucine, but amino acids such as arginine, lysine, ornithine, α-ketoglutaric acid, malic acid, oxaloacetic acid, pyruvin. It is known that the survival rate does not increase by the single administration of an organic acid such as an acid (see Patent Document 7).
JP-A-63-141562 JP-A-2-138128 Japanese Patent Laid-Open No. 5-170659 Japanese Patent Laid-Open No. 6-14751 JP-A-6-256201 Japanese Patent Laid-Open No. 2001-58952 Japanese Patent Application Laid-Open No. 61-50917

Drugs, functional foods, and the like that create a comfortable drinking state of suppressing a drought state by suppressing an increase in blood alcohol concentration after drinking and enjoying moderate intoxication are desired.
That is, an object of the present invention is to provide a composition for suppressing an increase in blood alcohol concentration.

The present invention relates to the following (1) to (14).
(1) A composition for suppressing an increase in blood alcohol concentration, comprising a basic amino acid or a salt thereof as an active ingredient.
(2) The composition according to (1), wherein the basic amino acid is ornithine, arginine, lysine, histidine, or citrulline.
(3) The composition of the above (1) or (2) containing an organic acid.
(4) The composition according to (3), wherein the organic acid is acetic acid, lactic acid, malic acid, fumaric acid, tartaric acid, or citric acid.
(5) The composition according to any one of (1) to (4) above, wherein the composition is a pharmaceutical or food additive.
(6) Food / beverage products containing the food additive of said (5).
(7) A method for suppressing an increase in blood alcohol concentration, comprising administering or ingesting an effective amount of a basic amino acid or a salt thereof to a subject in need.
(8) The method according to (7) above, wherein the basic amino acid is ornithine, arginine, lysine, histidine, or citrulline.
(9) The method according to (7) or (8) above, further comprising administering or ingesting an organic acid.
(10) The method according to (9) above, wherein the organic acid is acetic acid, lactic acid, malic acid, fumaric acid, tartaric acid, or citric acid.
(11) Use of a basic amino acid or a salt thereof for the production of a composition for suppressing an increase in alcohol blood concentration.
(12) Use of said (11) whose basic amino acid is ornithine, arginine, lysine, histidine, or citrulline.
(13) Use of (11) or (12) above, further comprising using an organic acid.
(14) Use of said (13) whose organic acid is an acetic acid, lactic acid, malic acid, fumaric acid, tartaric acid, or a citric acid.

  The present invention can provide a safe and effective composition for suppressing an increase in blood alcohol concentration, which contains a basic amino acid or a salt thereof as an active ingredient.

FIG. 1 is a graph showing the inhibitory effect of ornithine on the increase in blood ethanol concentration after ethanol intake. In the graph, ▪ represents the control group, ○ represents Test Group 1 (ingestion of ornithine hydrochloride), and Δ represents Test Group 2 (ingestion of ornithine hydrochloride and citric acid). The vertical axis represents blood ethanol concentration (g / L), and the horizontal axis represents elapsed time (hours) after ethanol intake. * And ** indicate that there is a significant difference with respect to the control group at a risk rate of less than 5% and 1%, respectively, in Student's t-test.

FIG. 2 is a graph showing the inhibitory effect of histidine on the increase in blood ethanol concentration after ethanol intake. In the graph, ▪ represents the control group, ○ represents Test Group 1 (histidine intake), and Δ represents Test Group 2 (histidine hydrochloride intake). The vertical axis represents blood ethanol concentration (g / L), and the horizontal axis represents elapsed time (hours) after ethanol intake. * Represents a significant difference from the control group at a risk rate of less than 5% in Student's t-test.

FIG. 3 is a graph showing the inhibitory effect of lysine or citrulline on the increase in blood ethanol concentration after ethanol intake. In the graph, ▪ represents the control group, Δ represents Test Group 1 (lysine citrate intake), and ○ represents Test Group 2 (citrulline intake). The vertical axis represents blood ethanol concentration (g / L), and the horizontal axis represents elapsed time (hours) after ethanol intake. * Represents a significant difference from the control group at a risk rate of less than 5% in Student's t-test.

FIG. 4 is a graph showing the effect of lysine on suppressing blood ethanol elevation after ethanol intake. In the graph, ■ represents the control group, and ○ represents the test group 1 (lysine hydrochloride intake). The vertical axis represents blood ethanol concentration (g / L), and the horizontal axis represents elapsed time (hours) after ethanol intake. * Represents a significant difference from the control group at a risk rate of less than 5% in Student's t-test.

FIG. 5 is a graph showing the inhibitory effect of arginine on blood ethanol elevation after ethanol intake. In the graph, ■ represents the control group, and ○ represents the test group 1 (arginine intake). The vertical axis represents blood ethanol concentration (g / L), and the horizontal axis represents elapsed time (hours) after ethanol intake. * Represents a significant difference from the control group at a risk rate of less than 5% in Student's t-test.

  The basic amino acid used in the present invention includes ornithine, arginine, lysine, histidine, citrulline and the like, and ornithine is preferred. The basic amino acids may be used alone or in a mixture of two or more. The basic amino acid may be any of L-form, D-form, and a mixture of L-form and D-form, but preferably L-form.

Examples of basic amino acid salts include acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts, and the like.
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.
Examples of the organic acid used in the present invention include acetic acid, lactic acid, malic acid, fumaric acid, tartaric acid, and citric acid. Acetic acid or citric acid is preferable, and citric acid is more preferable. In addition, the above organic acids may be used alone or as a mixture of two or more.

  The composition of the present invention may contain the above basic amino acid or a salt thereof as an active ingredient, and may further contain the above organic acid. When the composition of the present invention contains an organic acid, the blending weight ratio of the basic amino acid or salt thereof to the organic acid is preferably 1 to 0.01 to 100, more preferably 1 to 0.1 to 10, Especially preferably, it is 1: 1 to 1.5.

The composition of the present invention can be used as a pharmaceutical or food additive (hereinafter also referred to as the pharmaceutical or food additive of the present invention).
When the composition of the present invention is used as a medicine, the basic amino acid or a salt thereof can be administered as it is, but it is usually desirable to provide it as various preparations.

  The preparation contains a basic amino acid or a salt thereof as an active ingredient, but may further contain any other active ingredient for treatment. These pharmaceutical preparations are produced by any method well known in the technical field of pharmaceutics by mixing an active ingredient with one or more pharmacologically acceptable carriers.

As the dosage form of the preparation, it is desirable to use the most effective form in treatment, and oral administration or parenteral administration such as intravenous, intraperitoneal or subcutaneous administration can be mentioned, but oral administration is preferred.
Examples of dosage forms to be administered include tablets, powders, granules, pills, suspensions, emulsions, soaking and 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.

  Liquid preparations such as syrups suitable for oral administration include saccharides such as water, sucrose, sorbitol, fructose, glycols such as polyethylene glycol, propylene glycol, oils such as sesame oil, olive oil, soybean oil, p -Preservatives such as hydroxybenzoic acid esters, paraoxybenzoic acid derivatives such as methyl paraoxybenzoate, preservatives such as sodium benzoate, and flavors such as strawberry flavor and peppermint can be added to prepare a preparation.

  Also suitable for oral administration, such as tablets, powders and granules, are sugars such as lactose, sucrose, glucose, sucrose, mannitol, sorbitol, starches such as potato, wheat, corn, calcium carbonate, calcium sulfate, hydrogen carbonate Inorganic substances such as sodium and sodium chloride, excipients such as crystalline cellulose, licorice powder, gentian powder, etc., starch, agar, gelatin powder, crystalline cellulose, carmellose sodium, carmellose calcium, calcium carbonate, sodium bicarbonate , Disintegrants such as sodium alginate, magnesium stearate, talc, hydrogenated vegetable oil, macrogol, silicone oil and other lubricants, polyvinyl alcohol, hydroxypropylcellulose, methylcellulose, ethylcellulose, carmellose, gelatin, starch Ri binders such as liquid, surfactants such as fatty acid esters can be formulated by adding a plasticizer such as glycerin.

Suitable for parenteral administration, for example injections, comprise a sterile aqueous preparation containing a basic amino acid or salt thereof, preferably 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.
In these parenterals, one kind selected from the preservatives, preservatives, flavors, excipients, disintegrants, lubricants, binders, surfactants, plasticizers and the like exemplified in the oral preparations. Or more auxiliary components can be added.

The concentration of the basic amino acid or a salt thereof in the medicament of the present invention is appropriately selected according to the type of the preparation, the effect expected by administration of the preparation, and the like. 1 to 100% by weight, preferably 0.5 to 80% by weight, particularly preferably 1 to 70% by weight.
The dose and frequency of administration of the medicament of the present invention vary depending on the administration form, patient age, body weight, nature or severity of the symptoms to be treated, but are usually usually used as basic amino acids or salts thereof per adult day. It is administered once to several times a day so as to be 50 mg to 30 g, preferably 100 mg to 10 g, particularly preferably 200 mg to 3 g.
The administration period is not particularly limited, but is usually 1 day to 1 year, preferably 1 week to 3 months.

When the composition of the present invention is used as a food additive, it is possible to use a basic amino acid or a salt thereof as it is, but it contains a basic amino acid or a salt thereof as an active ingredient in the same manner as the above preparation. A food additive may be prepared.
The food additive of the present invention is processed or manufactured by mixing or dissolving other food additives as required, for example, in the form of powder, granules, pellets, tablets, or various liquids.

The food / beverage products containing the food additive of the present invention (hereinafter also referred to as the food / beverage product of the present invention) use a general method for producing a food / beverage product, except that the food additive of the present invention is added to the food / beverage product. Thus, it can be processed and manufactured.
The food and drink of the present invention are, for example, fluidized bed granulation, stirring granulation, extrusion granulation, rolling granulation, airflow granulation, compression molding granulation, pulverization granulation, spray granulation, spray granulation, etc. Granulation method, coating method such as pan coating, fluidized bed coating, dry coating, puff drying, excess steam method, foam mat method, expansion method such as microwave heating method, extrusion method such as extrusion granulator and extruder etc. It can also be manufactured using.

  Examples of the food and drink of the present invention include dairy products such as juices, soft drinks, teas, lactic acid bacteria beverages, fermented milk, frozen desserts, butter, cheese, yogurt, processed milk, skim milk, ham, sausage, hamburger and the like. Livestock meat products, fish paste products such as bamboo shoots, bamboo rings and fried fish, egg products such as broiled and egg tofu, cookies, jelly, chewing gum, candy, snacks and other confectionery, breads, noodles, pickles, salmon products, dried fish, It may be in any form such as boiled salmon, salted products, soups, seasonings and the like.

The food and drink of the present invention may be in the form of, for example, powdered food, sheet food, bottled food, canned food, retort food, capsule food, tablet food, liquid food, and drink.
The food / beverage products of the present invention can be used as food / beverage products such as health foods, functional foods, dietary supplements, foods for specified health use, etc., for suppressing the increase in blood alcohol concentration.

The food additive or food / beverage product of the present invention includes additives generally used in food / beverage products, such as sweeteners described in the Food Additives Display Handbook (Japan Food Additives Association, issued on January 6, 1997). , Coloring agent, Preservative, Thickening stabilizer, Antioxidant, Coloring agent, Bleaching agent, Antifungal agent, Gum base, Bittering agent, Enzyme, Brightener, Acidulant, Seasoning, Emulsifier, Strengthening agent, Production agent A fragrance, a spice extract, etc. may be added.
The amount of the food additive of the present invention added to the food or drink of the present invention is appropriately selected according to the type of food or drink, the effect expected from the intake of the food or drink, etc. In general, it is added so as to contain 0.1 to 90% by weight, preferably 0.5 to 80% by weight, particularly preferably 1 to 70% by weight.

The intake of the food and drink according to the present invention varies depending on the intake form, the age of the intake, the body weight, etc., but is usually 50 mg-30 g, preferably 100 mg- It is taken once to several times a day so as to be 10 g, more preferably 200 mg to 3 g.
The intake period is not particularly limited, but is usually 1 day to 1 year, preferably 1 week to 3 months.
An increase in blood alcohol concentration can be suppressed by administering or ingesting the medicament or food or drink of the present invention before drinking, during drinking or after drinking.
Below, the test example which investigated the blood alcohol level raise inhibitory effect by a basic amino acid is shown.

Test example 1
In the test, DBA / 2Cr mice (male, 7 weeks old, purchased from Japan SLC) were used. Breeding conditions were room temperature 22 ± 2 ° C., humidity 35 ± 15%, and free intake of feed and water.
Each test group consisted of 5 mice. First, ethanol was orally administered at 4 g / kg body weight, and 30 minutes later, distilled water was given to the control group mice, and 1 kg body weight was given to the test group 1 mice. An aqueous solution prepared so as to ingest 2 g of ornithine hydrochloride (manufactured by Kyowa Hakko Kogyo Co., Ltd.) per mouse was added to 0.935 g of ornithine hydrochloride and 1.065 g of citric acid (kg of Wako Jun) An aqueous solution prepared so as to be ingested) was orally administered.

  From 1 hour to 4.5 hours after the start of ethanol administration, the ethanol concentration in the blood of each mouse was measured using F-kit ethanol (Roche Diagnostics), and the average value in each group was determined. Calculated. The significant difference test was performed by T test.

The results are shown in FIG. From FIG. 1, it was shown that in both Test Group 1 and Test Group 2, an increase in blood ethanol concentration after ethanol administration was significantly suppressed. In Test Group 2, the effect was particularly remarkable within 90 minutes after ethanol administration.
From the above results, the effect of ornithine on suppressing the increase in blood alcohol concentration was clarified.

Test example 2
In Test Example 1, an aqueous solution prepared such that 2 g of histidine (kg made by Kyowa Hakko Kogyo Co., Ltd.) per kg of body weight of test group 1 mice was prepared, and 2 g of histidine hydrochloride (Kyowa) per kg body weight of test group 2 mice. The same test as in Test Example 1 was conducted except that an aqueous solution prepared so as to be ingested was manufactured orally.

The results are shown in FIG. From FIG. 2, it was shown that in both Test Group 1 and Test Group 2, an increase in blood ethanol concentration after ethanol administration was significantly suppressed.
From the above results, the effect of suppressing the increase in blood alcohol concentration by histidine was clarified.

Test example 3
In Test Example 1, an aqueous solution prepared so as to ingest 2 g of lysine citrate (produced by Kyowa Hakko Kogyo Co., Ltd.) per kg of body weight in mice of test group 1 was used to give 2 g of citrulline (kg of body weight) to test group 2 mice. A test similar to Test Example 1 was conducted except that an aqueous solution prepared so as to ingest Kyowa Hakko Kogyo Co., Ltd. was orally administered.

The results are shown in FIG. FIG. 3 shows that in both test group 1 and test group 2, an increase in blood ethanol concentration is remarkably suppressed, particularly within 90 minutes after ethanol administration.
From the above results, the effect of lysine and citrulline on the increase in blood alcohol concentration was clarified.

Test example 4
In Test Example 1, a control group and a test group 1 were composed of two groups, except that an aqueous solution prepared to ingest 2 g of lysine hydrochloride (produced by Kyowa Hakko Kogyo Co., Ltd.) per kg of body weight of the test group 1 mice was orally administered. The same test as in Test Example 1 was performed.

The results are shown in FIG. FIG. 4 shows that in test group 1, an increase in blood ethanol concentration after ethanol administration was significantly suppressed.
From the above results, the effect of lysine on suppressing the increase in blood alcohol concentration was clarified.

Test Example 5
In Test Example 1, the control group and the test group 1 were composed of two groups, except that an aqueous solution prepared so as to ingest 1 g of arginine per kg body weight (produced by Kyowa Hakko Kogyo Co., Ltd.) into the mice of the test group 1 was orally administered. The same test as in Test Example 1 was performed.
The results are shown in FIG. FIG. 5 shows that in test group 1, the increase in blood ethanol concentration was remarkably suppressed, particularly within 90 minutes after ethanol administration.
From the above results, the effect of arginine in suppressing the increase in blood alcohol concentration was clarified.
Examples of the present invention are shown below.

Manufacture of tablets containing ornithine Ornithine hydrochloride 136.2kg (Kyowa Hakko Kogyo Co., Ltd., L-ornithine hydrochloride), microcrystalline cellulose 36.0kg (Asahi Kasei Chemicals Co., Ltd., Avicel FD101), sucrose fatty acid ester 6.6kg Conical, manufactured by Kogyo Seiyaku Co., Ltd., DK Ester F-20W), 1.2 kg of calcium phosphate (Taihei Chemical Industrial Co., Ltd., tricalcium phosphate) and 20.0 kg of β-cyclodextrin (manufactured by Nippon Shokuhin Kako Co., Ltd., Celdex B-100) It mixed using the blender (The Nippon Dryer Co., Ltd. make, CB-1200 blender). The obtained mixture was compression-molded using a rotary compression molding machine (VIRGO524SS1AY, manufactured by Kikusui Seisakusho Co., Ltd.) at a compression molding pressure of 10 kN to produce tablets with a diameter of 8 mm and 250 mg.

Manufacture of tablets containing ornithine and citric acid 1000g of citric acid (Kyowa High Foods) 1000g, ornithine hydrochloride 1000g, and reduced maltose syrup (manufactured by Hayashibara Shoji Co., Ltd.) A mixture of 2747.5 g of powdered mabit 50M) was granulated with a fluidized bed granulation dryer (FLO-5, manufactured by Freund Sangyo Co., Ltd.) using water. To 4557.6 g of the obtained granulated product, 2.4 g of sucralose (manufactured by Saneigen FFI Co., Ltd.) and 240 g of sucrose fatty acid ester (manufactured by Nagase Sangyo Co., Ltd., DK ester F-20W) were mixed. The obtained mixture was compression-molded at a compression molding pressure of 10 kN using a rotary compression molding machine to produce tablets with a diameter of 9 mm and 300 mg.

Manufacture of beverages containing ornithine and citric acid Ornithine hydrochloride 1.28 kg, erythritol 3 kg (manufactured by Nikken Chemical), citric acid 0.05 kg, artificial sweetener 3 g, and fragrance 0.06 kg are stirred and dissolved in 50 L of water at a liquid temperature of 70 ° C. Then, the pH was adjusted to 3.3 with citric acid, sterilized using plate sterilization, filled into a bottle, and then pasteurized, to produce a beverage containing ornithine and citric acid.

  The present invention can provide a safe and effective composition for suppressing an increase in blood alcohol concentration, which contains a basic amino acid or a salt thereof as an active ingredient.

Claims (14)

  A composition for suppressing an increase in blood alcohol concentration, comprising a basic amino acid or a salt thereof as an active ingredient.   The composition according to claim 1, wherein the basic amino acid is ornithine, arginine, lysine, histidine, or citrulline.   The composition of Claim 1 or 2 containing an organic acid.   The composition according to claim 3, wherein the organic acid is acetic acid, lactic acid, malic acid, fumaric acid, tartaric acid, or citric acid.   The composition according to any one of claims 1 to 4, wherein the composition is a pharmaceutical or food additive.   Food / beverage products containing the food additive of Claim 5.   A method for suppressing an increase in blood alcohol concentration, comprising administering or ingesting an effective amount of a basic amino acid or a salt thereof to a subject in need thereof.   The method according to claim 7, wherein the basic amino acid is ornithine, arginine, lysine, histidine, or citrulline.   The method according to claim 7 or 8, further comprising administering or ingesting an organic acid.   The method according to claim 9, wherein the organic acid is acetic acid, lactic acid, malic acid, fumaric acid, tartaric acid, or citric acid.   Use of a basic amino acid or a salt thereof for the manufacture of a composition for suppressing an increase in blood alcohol concentration.   The use according to claim 11, wherein the basic amino acid is ornithine, arginine, lysine, histidine, or citrulline.   13. Use according to claim 11 or 12, comprising further use of an organic acid.   The method according to claim 13, wherein the organic acid is acetic acid, lactic acid, malic acid, fumaric acid, tartaric acid, or citric acid.

Images