WO2007108071A1 - Antistress composition and food and drink containing the same - Google Patents

Antistress composition and food and drink containing the same Download PDF

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Publication number
WO2007108071A1
WO2007108071A1 PCT/JP2006/305418 JP2006305418W WO2007108071A1 WO 2007108071 A1 WO2007108071 A1 WO 2007108071A1 JP 2006305418 W JP2006305418 W JP 2006305418W WO 2007108071 A1 WO2007108071 A1 WO 2007108071A1
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WO
WIPO (PCT)
Prior art keywords
acid
triphosphate
diphosphate
inosine
nucleic acid
Prior art date
Application number
PCT/JP2006/305418
Other languages
French (fr)
Japanese (ja)
Inventor
Kazuya Watabe
Minako Suga
Itadaki Yamaguchi
Yoshihiro Yoshida
Original Assignee
Pharma Foods International Co., Ltd.
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Publication date
Application filed by Pharma Foods International Co., Ltd. filed Critical Pharma Foods International Co., Ltd.
Priority to PCT/JP2006/305418 priority Critical patent/WO2007108071A1/en
Publication of WO2007108071A1 publication Critical patent/WO2007108071A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/03—Organic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • Anti-stress composition and food and drink containing the same
  • the present invention relates to an anti-stress composition containing ⁇ -aminobutyric acid and a nucleic acid-related compound as active ingredients. More specifically, the present invention relates to an anti-stress composition that can be used to suppress or reduce fatigue due to mental stress, that is, to prevent or improve the health disorder caused by it.
  • Patent Document 1 discloses a food and drink for mental stability characterized by containing creatine.
  • Patent Document 2 is selected as a nucleic acid-related substance that also has uridylic acid, uridine, and uracilca
  • Patent Document 3 discloses a recovery agent for cerebral fatigue based on a high level of mental activity inherent in humans, comprising theanine as an active ingredient.
  • Patent Document 4 discloses an anti-fatigue composition characterized by containing Coenzyme Q10, carcin and an organic acid.
  • Patent Document 5 discloses an ⁇ -wave release enhancer comprising notinose.
  • Patent Document 6 discloses a mental fatigue reducing composition containing a mixed component comprising caffeine, theanine and arginine as an active ingredient.
  • Patent Document 7 discloses a stress-improving food characterized by containing a composition comprising a food material containing at least dartathione and one or more of other antioxidants.
  • Patent Document 8 discloses an anti-stress composition in which specific nucleic acid components are combined.
  • Patent Document 9 discloses an anti-stress composition comprising ⁇ -strength rotin as an active ingredient.
  • GABA ⁇ -aminobutyric acid
  • Patent Document 10 discloses a healing effect composition characterized by containing GABA as an active ingredient.
  • the sine wave the brain wave that increases in appearance in the relaxed state
  • 8 waves the brain wave that appears in the state of awakening, excitement, and V. It is clear that it is reduced and V, the so-called “healing state” force S is brought about.
  • Patent Document 11 discloses a dopamine release inhibiting composition characterized by containing GABA as an active ingredient. It was also clarified that by taking GABA orally, excessive release of dopamine caused by stress, etc. can be suppressed, and the balance between excitatory substances and inhibitory substances in the central nervous system can be improved.
  • Patent Document 12 discloses a composition for improving immunity characterized by containing GABA as an active ingredient. And by taking GABA orally, mental and physical stress It is clarified that immunity decline caused by can be improved.
  • Patent Document 13 discloses a food and drink having a relaxing effect characterized by containing GABA as an active ingredient and containing cacao or a cacao-derived raw material. And it is clarified that a higher relaxing effect can be obtained by ingesting the food and drink.
  • Patent Document 1 Japanese Patent Laid-Open No. 2005-348720
  • Patent Document 2 JP-A-2005-330213
  • Patent Document 3 Japanese Patent Laid-Open No. 2005-187344
  • Patent Document 4 Japanese Patent Laid-Open No. 2005-97161
  • Patent Document 5 Japanese Unexamined Patent Publication No. 2004-2383
  • Patent Document 6 Japanese Unexamined Patent Publication No. 2002-322063
  • Patent Document 7 JP-A-8-275575
  • Patent Document 8 JP-A-7-215879
  • Patent Document 9 JP-A-6-65068
  • Patent Document 10 Japanese Patent Laid-Open No. 2003-252755
  • Patent Document 11 Japanese Patent Laid-Open No. 2003-252756
  • Patent Document 12 Japanese Unexamined Patent Publication No. 2003-327528
  • Patent Document 13 Japanese Unexamined Patent Publication No. 2005-348656
  • the object of the present invention can be easily blended into various foods and drinks with high safety, efficiently suppressing and reducing mental fatigue, and prevention of health disorders resulting therefrom. Break
  • the object is to provide an anti-stress composition that can be expected to have a good effect.
  • the anti-stress composition of the present invention is characterized by containing GABA and a nucleic acid-related compound as active ingredients.
  • the antistress composition of the present invention preferably contains GABA and a nucleic acid-related compound in a mass ratio of 1: 0.0001 to 1: 0.1.
  • the nucleic acid-related compound may be uracil, uridine, uridylic acid (UMP), uridine 5'-diphosphate (UDP), uridine 5'-triphosphate (UTP), adenine, adenosine, adenyl.
  • AMP adenosine 5'-diphosphate
  • ADP adenosine 5'-triphosphate
  • ATP inosine
  • IMP inosine acid
  • IDP inosine 5'-diphosphate
  • IDP inosine 5 '—Triphosphate
  • Deoxyuridine Deoxyuridylate
  • dUDP Deoxyuridine 5'—Diphosphate
  • dUTP Deoxyuridine 5'—Triphosphate
  • Deoxyadenosine, Deoxyadenylate (dAMP) Deoxyadenosine 5′-diphosphate (dADP), deoxyadenosine 5′-triphosphate (dATP), deoxyinosine, deoxyinosinic acid (dIMP), deoxyinosine 5′-diphosphate (dIDP), Deoxyinosine 5'-triphosphate (dITP), xanthine and their
  • it is at least one selected from the group of salt power.
  • the antistress composition of the present invention can exhibit a higher antistress effect by containing GABA and a nucleic acid-related compound as active ingredients.
  • the food and drink of the present invention is characterized by containing the anti-stress composition, which makes it easy to ingest the anti-stress composition of the present invention on a daily basis. It is expected to effectively suppress and reduce fatigue, and to prevent and improve health problems caused by it.
  • FIG. 1 A diagram showing the results of measuring the effect of saliva on the amount of chromogranin A in the case where GABA and a nucleic acid-related compound are ingested singly or in combination and are loaded with psychic stress. It is. BEST MODE FOR CARRYING OUT THE INVENTION
  • mental stress means mental state such as tension, anxiety, fear and loneliness, as well as mental work in human relations and work.
  • Anti-stress action refers to 1) suppressing or reducing mental fatigue caused by mental stress as described above 2) various health disorders caused by mental fatigue, such as immune function It means that prevention, improvement effects such as decline, hormonal balance disturbance, emotional anxiety, and sleep disorders can be expected.
  • chromogranin A in saliva is used as an index of the antistress action.
  • CgA Cerebral gA
  • saliva saliva does not change even when exposed to physical stress, but increases when exposed to mental stress, so it can be used as a mental stress index (Toyota Central Research).
  • GABA which is one of the active ingredients of the anti-stress composition of the present invention, is one of non-protein amino acids widely distributed in nature, such as tea, vegetables, cereals, kimchi, etc. It is a component normally contained in fermented foods. Also, it is known that glutamate is produced by decarboxylation in the living body, and in the human body, it is known to be present in high concentrations especially in the substantia nigra, basal ganglia, hypothalamus, etc. It is a highly safe substance.
  • the GABA used in the present invention is not particularly limited as long as it can be used in foods.
  • glutamate decarboxylase is a method using plants or microorganisms containing the enzyme, as well as chemical synthesis. It is possible to use a product obtained by a known method such as a method or a method of extracting from a raw material containing a relatively large amount of GABA such as germinated brown rice.
  • glutamic acid decarboxylase is preferably used GABA obtained by a method using a plant or microorganism containing the enzyme.
  • JP-A-2003-70462 can be preferably exemplified. That is, a culture solution (pH4.) Containing glutamic acid or sodium glutamate and glucose, yeast extract, sodium acetate, magnesium sulfate, etc. 0 to 7.0) was added with a culture solution of Lactobacillus hilgardii K-3 (Lactobacillus hilgardii K-3 strain, FERM BP-10487) and cultured at 20 to 30 ° C for 1 to 3 days.
  • a culture solution pH4.
  • Lactobacillus hilgardii K-3 Lactobacillus hilgardii K-3 strain, FERM BP-10487
  • the fermented broth (GABA content in the fermented broth is about 5% by mass, and about 70% by mass GABA when converted to solid content) is sterilized by heating and filtered through a filter to obtain a filtrate.
  • GABA can be obtained by concentrating as it is, or by further drying.
  • GABA may be further purified by subjecting the filtrate to a treatment such as column chromatography.
  • the GABA content in the fermentation broth obtained as described above can be measured using analytical equipment such as high performance liquid chromatography (HPLC) and an amino acid measuring instrument according to a conventional method. For example, after appropriately diluting (100-fold to 10,000-fold) the sample with 0.2N sodium citrate buffer (pH 2.2), the solid is removed by centrifugation or filtration to prepare a measurement sample. Can be measured.
  • HPLC high performance liquid chromatography
  • amino acid measuring instrument amino acid measuring instrument
  • Mobile phase buffer “Amino acid mobile phase kit Na type” (trade name, manufactured by Shimadzu Corporation), mobile phase flow rate: 0.4 mL / min
  • Reaction phase 1 0.04% sodium hypochlorite solution (pH 10 boric acid-carbonate buffer 500mL vs hypochlorous acid 0.2mL)
  • Reaction Phase 2 “Amino Acid Analysis Kit OPA Reagent Reaction Layer” (trade name, manufactured by Shimadzu Corporation)
  • the nucleic acid-related compound that is another active ingredient of the anti-stress composition of the present invention is a nucleobase, nucleoside, nucleotide, nucleic acid, or a derivative thereof (oligonucleoside, oligonucleotide, sugar nucleotide, etc.) or metabolism. It means a product and the like, and specifically, the following compounds can be exemplified.
  • Nucleobase Adenine, guanine, cytosine, thymine, uracil, etc.
  • Ribonucleosides adenosine, guanosine, cytidine, uridine, inosine, xanthosine, etc.
  • Deoxyribonucleosides Deoxyadenosine, Deoxyguanosine, Deoxycytidine, Deoxythymidine, Deoxyuridine, Deoxyinosine, etc.
  • adenylate adenosine 5'-diphosphate (ADP), adenosine 5 'triphosphate (ATP), guarate (GMP), guanosine 5'-diphosphate (GDP) ), Guanosine 5 'triphosphate (GTP), cytidylic acid (CMP), cytidine 5'-diphosphate (CDP), cytidine 5'- triphosphate (CTP), uridylic acid (UMP), uridine 5' —Diphosphate (UDP), uridine 5′—triphosphate (UTP), inosine acid (IMP), inosine 5′—diphosphate (IDP), inosine 5′—triphosphate (ITP), xanthylic acid ( XMP) etc.
  • AMP adenylate
  • ADP adenosine 5'-diphosphate
  • ATP adenosine 5 'triphosphate
  • Deoxyribonucleotides Deoxyadelic acid (dAMP), Deoxyadenosine 5'—Diphosphate (dADP), Deoxyadenosine 5'-Triphosphate (dATP), Deoxygualuic acid (d GMP), deoxyguanosine 5'-diphosphate (dGDP), deoxyguanosine 5'-triphosphate (d GTP), deoxycytidylic acid (dCMP), deoxycytidine 5'-diphosphate (dCDP), de Oxycytidine 5'-triphosphate (dCTP), Deoxythymidylic acid (dTMP), Deoxythymidine 5 'Diphosphate (dTDP), Deoxythymidine 5'-Triphosphate (dTTP), Deoxyuridylic acid (dU MP), Deoxyuridine 5'- Diphosphate (dUDP), Deoxyuridine 5'-Triphosphate (dUTP), Deoxyinosinic acid (dIMP), De
  • Salts of the compounds exemplified in the above 0 to vi) sodium salts, potassium salts, calcium salts
  • nucleic acid-related compounds uracil, uridine, uridylic acid (UMP), uridine 5′-diphosphate (UDP), uridine 5′-triphosphate (UTP), adenine, adenosine, adenine.
  • AMP adenosine 5'-diphosphate
  • ADP adenosine 5'-triphosphate
  • ATP inosine
  • IMP inosine acid
  • IDP inosine 5'-diphosphate
  • IDP inosine 5'-Triphosphate
  • Deoxyuridine Deoxyuridylic acid
  • dUDP Deoxyuridine 5'-Diphosphate
  • dUTP Deoxyuridine 5'-Triphosphate
  • Deoxyadenosine Deoxyadede -Luric acid (dAMP)
  • DAMP Deoxyadenosine 5 '-Diphosphate
  • dATP Deoxyinosine
  • Deoxyinosinic acid dIMP
  • DIDP Deoxyinosine 5 'Monodiphosphate
  • DITP deoxyinosine 5′-triphosphate
  • xanthine and salts thereof can be preferably
  • the composition containing the nucleic acid-related compound includes salmon roe, boiled and dried bonito, dried sardine, dried shiitake (or extracts thereof), yeast extract, hard meat extract, livestock meat extract, Seafood extracts, embryos and the like can also be used.
  • the analysis and quantification of the nucleic acid-related compound can be performed by a known method such as HPLC, and for example, can be performed by HPLC under the following conditions.
  • the anti-stress composition of the present invention may contain GABA and the nucleic acid-related compound in a mass ratio of 1: 0.0001 to 1: 0.1, preferably in a mass ratio of 1: 0.0003 to 1: 0.05. It is more preferable to contain it at a mass ratio of 1: 0.00045 to 1: 0.01. If the content ratio of GABA and the nucleic acid-related compound is outside the above range, a higher anti-stress action may not be obtained, and the taste may be strong and may be added to food and drink.
  • the antistress composition of the present invention includes theanine, theopromine, various herbs (for example, chamomile, lavender, St. John's wort, passion flower, hop, valerian) and its It contains physiologically active components having anti-stress action such as extracts, and other amino acids, peptides, excipients, sugars, oligosaccharides, emulsifiers, acidulants, sweeteners, flavors, minerals, vitamins, etc. Can do.
  • physiologically active components having anti-stress action such as extracts, and other amino acids, peptides, excipients, sugars, oligosaccharides, emulsifiers, acidulants, sweeteners, flavors, minerals, vitamins, etc. Can do.
  • the form is particularly limited.
  • a solution, a powder, a granule, a tablet, a capsule and the like may be appropriately selected depending on the application.
  • the effective intake of the anti-stress composition of the present invention varies depending on the degree of mental fatigue, age, weight, etc., and thus cannot be determined unconditionally, but usually 10 to 3000 mg of GABA per day, nucleic acid
  • the related compound is 0.001 to 300 mg, preferably 30 to 100 mg as GABA per day and 0.003 to 100 mg as the nucleic acid related compound (however, the intake ratio of GABA and the nucleic acid related compound is 1: 0.0001 to 1 by mass ratio) : It should be 0.1! /,).
  • the antistress composition of the present invention includes, for example, soft drinks, jelly drinks, milk drinks, lactic acid bacteria drinks, cocoa drinks, coffee drinks, tea drinks, soy milk drinks, alcoholic drinks (for example, beer, chews, cocktails, Liqueur etc.), soup, dairy products (eg yogurt, ice cream), confectionery (eg cookies, biscuits, wafers, jelly, pudding, chocolate, gum, candy, soft candy, caramel, tablet confectionery, etc.), bread It can be combined with various foods and drinks such as potatoes, supplements, retort foods (eg, curry, porridge), frozen foods, and dressings.
  • alcoholic drinks for example, beer, chews, cocktails, Liqueur etc.
  • soup dairy products
  • confectionery eg cookies, biscuits, wafers, jelly, pudding, chocolate, gum, candy, soft candy, caramel, tablet confectionery, etc.
  • bread eg cookies, biscuits, wafers, jelly, pudding, chocolate, gum, candy, soft candy, caramel, tablet confectionery, etc.
  • bread can be
  • the amount of the antistress composition of the present invention in a food or drink cannot be determined unconditionally because it varies depending on the form of the food or drink, but the above effective intake of GABA and a nucleic acid-related compound are ingested in a single meal. It is preferable to mix it as possible.
  • timing and method of addition of the antistress composition of the present invention in various foods and beverages are not particularly limited, and the initial power may be added together with other raw materials during the manufacturing process. May be added later.
  • the anti-stress action was measured using the amount of CgA in saliva as an index in a human volunteer test.
  • GABA is pure (100% purity), and the GABA content in each sample is the minimum that can be expected to have an anti-stress effect when GABA is ingested alone to see the effects of nucleic acid-related compounds. The amount was close.
  • Sample 1 Pure GABA (30mg) / water lOOmL •
  • Sample 2 Nucleic acid related compound (uracil: 0.014mg, ATP: 0.014mg) Z water lOOmL •
  • Sample 3 Pure GABA (30mg) + Nucleic acid related compound (uracil: 0.014mg) Z water lOOmL •
  • Sample 4 Pure product GABA (30mg) + Nucleic acid related compounds (uracil: 0.014mg, ATP: 0.014mg) Z water lOOmL
  • Subject (4 persons) ingested sample 1 above, and after taking a rest time of 15 minutes, mental arithmetic test using Uchida-Kraepelin test (standard type) (manufactured by Japan Institute of Psychiatric Technology) Stressed mental stress by running for 15 minutes. After a 5-minute break, another 15-minute Kraepelin mental arithmetic test was performed. Each subject was tested three times, immediately before the sample intake (0 minutes), immediately after the end of the first Kraperin mental arithmetic test (30 minutes after the sample intake), and immediately after the end of the second Creperin mental arithmetic test (50 minutes after the sample intake). Saliva was collected using “Sullivet” (trade name, manufactured by SARSTEDT).
  • CgA contained in the collected saliva is measured using the “YK070 human 'chromogranin A EIA kit” (trade name, manufactured by Yauchihara Laboratories), and the amount of CgA in the saliva immediately before sample intake (0 min) is measured. Based on the standard (100%), the average rate of change (%) in the amount of CgA in saliva at each time after sample intake was determined.
  • the anti-stress composition of the present invention and food and drink containing the same can be used as health foods and the like that improve mental health, and can be used by students who are exposed to mental stress who are often exposed to mental stress. Is preferred.

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Abstract

An antistress composition of the invention contains Ϝ-aminobutyric acid and a nucleic acid-related compound as active ingredients and it preferably contains Ϝ-aminobutyric acid and the nucleic acid-related compound in a mass ratio of 1:0.0001 to 1:0.1. The nucleic acid-related compound is preferably at least one type selected from the group consisting of uracil, uridine, uridylic acid (UMP), uridine 5’-diphosphate (UDP), uridine 5’-triphosphate (UTP), adenine, adenosine, adenylic acid (AMP), adenosine 5’-diphosphate (ADP), adenosine 5’-triphosphate (ATP), inosine, inosinic acid (IMP), inosine 5’-diphosphate (IDP), inosine 5’-triphosphate (ITP), deoxyuridine, deoxyuridylic acid (dUMP), deoxyuridine 5’-diphosphate (dUDP), deoxyuridine 5’-triphosphate (dUTP), deoxyadenosine, deoxyadenylic acid (dAMP), deoxyadenosine 5’-diphosphate (dADP), deoxyadenosine 5’-triphosphate (dATP), deoxyinosine, deoxyinosinic acid (dIMP), deoxyinosine 5’-diphosphate (dIDP), deoxyinosine 5’-triphosphate (dITP), xanthin and salts thereof. The antistress composition of the invention efficiently suppresses/decreases mental fatigue by oral intake, can be expected to have an effect of preventing/improving health disorder caused by the mental fatigue and can be easily formulated into various foods and drinks.

Description

明 細 書  Specification
抗ストレス組成物及びそれを含有する飲食品  Anti-stress composition and food and drink containing the same
技術分野  Technical field
[0001] 本発明は、 γーァミノ酪酸と核酸関連化合物を有効成分として含有する抗ストレス 組成物に関する。詳しくは、精神的なストレスによる疲労、すなわち精神的疲労を抑 制'軽減し、それに起因する健康障害の予防 ·改善効果が期待できる抗ストレス組成 物に関する。  [0001] The present invention relates to an anti-stress composition containing γ-aminobutyric acid and a nucleic acid-related compound as active ingredients. More specifically, the present invention relates to an anti-stress composition that can be used to suppress or reduce fatigue due to mental stress, that is, to prevent or improve the health disorder caused by it.
背景技術  Background art
[0002] 我々は生活環境や職場環境の多様化、人間関係の複雑ィ匕などにより、様々なスト レスにさらされている。ストレスは、通常、肉体的なストレスと精神的なストレスに大きく 分類されるが、現代人にとっては、肉体的なストレスよりも精神的なストレスの方が大 きいといわれる。  [0002] We are exposed to various stresses due to diversification of living and work environments and the complexity of human relationships. Stress is generally classified broadly into physical stress and mental stress, but for modern people, mental stress is said to be greater than physical stress.
[0003] 一般的に、過度の、あるいは継続的に精神的なストレスにさらされることによって精 神的疲労が蓄積すると、免疫機能の低下、ホルモンバランスの乱れ、情緒不安、睡 眠障害等の様々な健康障害が生じることが知られている。そのため、日常生活にお いて精神的疲労を軽減'解消してメンタルヘルスを改善することは非常に重要である  [0003] Generally, when mental fatigue accumulates due to excessive or continuous exposure to mental stress, various functions such as decline of immune function, disorder of hormone balance, emotional anxiety, sleep disorders, etc. It is known that serious health problems occur. Therefore, it is very important to reduce mental fatigue and improve mental health in daily life.
[0004] 従来より、精神的疲労を抑制，軽減し、それに起因する様々な健康障害を予防'改 善するための様々な方法が提案されているが、その効果に個人差があったり、継続 的に実施することが難し力つたりするものも多力つた。 [0004] Conventionally, various methods have been proposed for suppressing or reducing mental fatigue and preventing and improving various health disorders caused by the mental fatigue. There are many things that are difficult and difficult to implement.
[0005] そのため、精神的疲労やそれに起因する様々な健康障害を、より手軽に抑制 ·軽 減することを目的とした抗ストレス組成物や飲食品等が数多く提案されて ヽる。 [0005] For this reason, many antistress compositions and foods and drinks have been proposed for the purpose of more easily suppressing / reducing mental fatigue and various health disorders resulting therefrom.
[0006] 例えば、特許文献 1には、クレアチンを含有することを特徴とする精神安定用飲食 品が開示されている。 [0006] For example, Patent Document 1 discloses a food and drink for mental stability characterized by containing creatine.
特許文献 2には、ゥリジル酸、ゥリジン、ゥラシルカもなる核酸関連物質力 選ばれる Patent Document 2 is selected as a nucleic acid-related substance that also has uridylic acid, uridine, and uracilca
1種又は 2種以上を有効成分としてなることを特徴とする酸化ストレス抑制剤が開示さ れている。 特許文献 3には、テアニンを有効成分とするヒトに固有の高度な精神的活動に基づ く大脳疲労の回復剤が開示されている。 An oxidative stress inhibitor characterized by comprising one or more active ingredients as an active ingredient is disclosed. Patent Document 3 discloses a recovery agent for cerebral fatigue based on a high level of mental activity inherent in humans, comprising theanine as an active ingredient.
特許文献 4には、コェンザィム Q10、カル-チン及び有機酸を含有することを特徴と する抗疲労用組成物が開示されている。  Patent Document 4 discloses an anti-fatigue composition characterized by containing Coenzyme Q10, carcin and an organic acid.
特許文献 5には、ノ チノースを含んでなる α波放出増強剤が開示されている。 特許文献 6には、カフェイン、テアニン及びアルギニンからなる混合成分を有効成分 として含有する精神疲労軽減組成物が開示されて ヽる。  Patent Document 5 discloses an α-wave release enhancer comprising notinose. Patent Document 6 discloses a mental fatigue reducing composition containing a mixed component comprising caffeine, theanine and arginine as an active ingredient.
特許文献 7には、少なくともダルタチオンを含有する食品素材と他の抗酸化物質の うち一種又は二種以上とを組み合わせた組成物を含有することを特徴とするストレス 改善食品が開示されている。  Patent Document 7 discloses a stress-improving food characterized by containing a composition comprising a food material containing at least dartathione and one or more of other antioxidants.
特許文献 8には、特定の核酸構成成分を組み合わせた抗ストレス組成物が開示さ れている。  Patent Document 8 discloses an anti-stress composition in which specific nucleic acid components are combined.
特許文献 9には、 β一力ロチンを有効成分としてなる抗ストレス組成物が開示されて いる。  Patent Document 9 discloses an anti-stress composition comprising β-strength rotin as an active ingredient.
一方、本発明者らは、脳内に広く分布し、抑制系の神経伝達物質として知られてい る γ —ァミノ酪酸 (以下「GABA」という）の生理活性機能を研究する過程で、ヒトの精 神活動に与える様々な作用を見出し、以下のような提案を行っている。  On the other hand, in the process of studying the physiologically active function of γ-aminobutyric acid (hereinafter referred to as “GABA”), which is widely distributed in the brain and is known as an inhibitory neurotransmitter, the present inventors He found various effects on divine activities and made the following proposals.
例えば、特許文献 10において、 GABAを有効成分として含有することを特徴とする 癒し効果組成物を開示している。そして、 GABAを経口摂取することにより、ひ波（リラ ックス状態の時に出現が増加する脳波）が増強されると共に、）8波（覚醒し、興奮して V、る状態で出現する脳波）が減少し、 V、わゆる「癒し状態」力 Sもたらされることを明らか にしている。  For example, Patent Document 10 discloses a healing effect composition characterized by containing GABA as an active ingredient. In addition, by taking GABA orally, the sine wave (the brain wave that increases in appearance in the relaxed state) is strengthened, and 8 waves (the brain wave that appears in the state of awakening, excitement, and V). It is clear that it is reduced and V, the so-called “healing state” force S is brought about.
特許文献 11にお 、て、 GABAを有効成分として含有することを特徴とするドーパミン 遊離抑制組成物を開示している。そして、 GABAを経口摂取することにより、ストレス 等によって引き起こされるドーパミンの過剰な遊離を抑制し、中枢神経の興奮性物質 と抑制性物質のバランスを改善できることを明らかにしている。  Patent Document 11 discloses a dopamine release inhibiting composition characterized by containing GABA as an active ingredient. It was also clarified that by taking GABA orally, excessive release of dopamine caused by stress, etc. can be suppressed, and the balance between excitatory substances and inhibitory substances in the central nervous system can be improved.
特許文献 12にお ヽて、 GABAを有効成分として含有することを特徴とする免疫能改 善用組成物を開示している。そして、 GABAを経口摂取することにより、心身ストレス に起因する免疫能低下を改善できることを明らかにしている。 Patent Document 12 discloses a composition for improving immunity characterized by containing GABA as an active ingredient. And by taking GABA orally, mental and physical stress It is clarified that immunity decline caused by can be improved.
特許文献 13において、 GABAを有効成分として含有し、カカオ又はカカオ由来の原 料を含むことを特徴とするリラックス効果を有する飲食品を開示している。そして、該 飲食品を摂取することで、より高いリラックス効果が得られることを明らかにしている。 特許文献 1：特開 2005— 348720号公報  Patent Document 13 discloses a food and drink having a relaxing effect characterized by containing GABA as an active ingredient and containing cacao or a cacao-derived raw material. And it is clarified that a higher relaxing effect can be obtained by ingesting the food and drink. Patent Document 1: Japanese Patent Laid-Open No. 2005-348720
特許文献 2 :特開 2005— 330213号公報  Patent Document 2: JP-A-2005-330213
特許文献 3：特開 2005— 187344号公報  Patent Document 3: Japanese Patent Laid-Open No. 2005-187344
特許文献 4：特開 2005— 97161号公報  Patent Document 4: Japanese Patent Laid-Open No. 2005-97161
特許文献 5 :特開 2004— 2383号公報  Patent Document 5: Japanese Unexamined Patent Publication No. 2004-2383
特許文献 6：特開 2002— 322063号公報  Patent Document 6: Japanese Unexamined Patent Publication No. 2002-322063
特許文献 7：特開平 8— 275752号公報  Patent Document 7: JP-A-8-275575
特許文献 8：特開平 7— 215879号公報  Patent Document 8: JP-A-7-215879
特許文献 9：特開平 6— 65068号公報  Patent Document 9: JP-A-6-65068
特許文献 10：特開 2003— 252755号公報  Patent Document 10: Japanese Patent Laid-Open No. 2003-252755
特許文献 11：特開 2003— 252756号公報  Patent Document 11: Japanese Patent Laid-Open No. 2003-252756
特許文献 12 :特開 2003— 327528号公報  Patent Document 12: Japanese Unexamined Patent Publication No. 2003-327528
特許文献 13 :特開 2005— 348656号公報  Patent Document 13: Japanese Unexamined Patent Publication No. 2005-348656
発明の開示  Disclosure of the invention
発明が解決しょうとする課題  Problems to be solved by the invention
[0008] し力しながら、上記のような従来の抗ストレス組成物等は、呈味ゃ物性等の問題か ら効果が期待できる量を配合しにくい、適用できる飲食品が限定されてしまう、多量 に摂取した際に副作用が生じる場合がある、ヒトに適用した場合に充分満足できる効 果が得られないなど、実際の商品へ適用するには問題があるものも多力つた。 [0008] However, the conventional anti-stress compositions and the like as described above are difficult to blend in amounts that can be expected to be effective due to problems such as taste and physical properties, and applicable foods and drinks are limited. There were many problems that could cause problems when applied to actual products, such as when side effects may occur when consumed in large amounts, or when sufficient effects were not obtained when applied to humans.
[0009] また、高度化、かつ複雑ィ匕した現代社会においては、過度の、あるいは «続的に精 神的なストレスにさらされることがますます多くなつており、より優れた抗ストレス作用を 有する製品の開発が求められている。 [0009] In addition, in an advanced and complicated modern society, more and more continual exposure to spiritual stress is becoming more and more excellent, resulting in a superior anti-stress effect. There is a need for the development of products.
[0010] したがって、本発明の目的は、安全性が高ぐ様々な飲食品にも容易に配合するこ とができ、精神的疲労を効率よく抑制，軽減し、それに起因する健康障害の予防'改 善効果が期待できる抗ストレス組成物を提供することにある。 [0010] Therefore, the object of the present invention can be easily blended into various foods and drinks with high safety, efficiently suppressing and reducing mental fatigue, and prevention of health disorders resulting therefrom. Break The object is to provide an anti-stress composition that can be expected to have a good effect.
課題を解決するための手段  Means for solving the problem
[0011] 本発明者らは、 GABAの抗ストレス作用を研究する中で、 GABAと核酸を一緒に摂 取することにより、より高い抗ストレス作用が得られることを見出し、この知見に基づい て本発明を完成するに至った。  [0011] While studying the antistress effect of GABA, the present inventors found that a higher antistress effect can be obtained by taking GABA and nucleic acid together, and based on this finding, The invention has been completed.
[0012] すなわち、本発明の抗ストレス組成物は、 GABAと核酸関連化合物とを有効成分と して含有することを特徴とする。  That is, the anti-stress composition of the present invention is characterized by containing GABA and a nucleic acid-related compound as active ingredients.
[0013] 本発明の抗ストレス組成物においては、 GABAと核酸関連化合物を質量比で 1 : 0.0 001〜1： 0.1で含有することが好ましい。  [0013] The antistress composition of the present invention preferably contains GABA and a nucleic acid-related compound in a mass ratio of 1: 0.0001 to 1: 0.1.
[0014] また、前記核酸関連化合物が、ゥラシル、ゥリジン、ゥリジル酸 (UMP)、ゥリジン 5'— 二リン酸（UDP)、ゥリジン 5'—三リン酸（UTP)、アデニン、アデノシン、アデ-ル酸 (A MP)、アデノシン 5' -二リン酸 (ADP)、アデノシン 5' -三リン酸 (ATP)、イノシン、イノ シン酸（IMP)、イノシン 5'—二リン酸（IDP)、イノシン 5'—三リン酸（ITP)、デォキシゥリ ジン、デォキシゥリジル酸（dUMP)、デォキシゥリジン 5'—二リン酸（dUDP)、デォキシ ゥリジン 5'—三リン酸（dUTP)、デォキシアデノシン、デォキシアデニル酸（dAMP)、デ ォキシアデノシン 5' -二リン酸（dADP)、デォキシアデノシン 5' -三リン酸（dATP)、デ ォキシイノシン、デォキシイノシン酸（dIMP)、デォキシイノシン 5'—二リン酸（dIDP)、 デォキシイノシン 5'—三リン酸 (dITP)、キサンチン及びそれらの塩類力 なる群から 選ばれた少なくとも 1種であることが好ま 、。  [0014] The nucleic acid-related compound may be uracil, uridine, uridylic acid (UMP), uridine 5'-diphosphate (UDP), uridine 5'-triphosphate (UTP), adenine, adenosine, adenyl. Acid (AMP), adenosine 5'-diphosphate (ADP), adenosine 5'-triphosphate (ATP), inosine, inosine acid (IMP), inosine 5'-diphosphate (IDP), inosine 5 '—Triphosphate (ITP), Deoxyuridine, Deoxyuridylate (dUMP), Deoxyuridine 5'—Diphosphate (dUDP), Deoxyuridine 5'—Triphosphate (dUTP), Deoxyadenosine, Deoxyadenylate (dAMP) ), Deoxyadenosine 5′-diphosphate (dADP), deoxyadenosine 5′-triphosphate (dATP), deoxyinosine, deoxyinosinic acid (dIMP), deoxyinosine 5′-diphosphate (dIDP), Deoxyinosine 5'-triphosphate (dITP), xanthine and their Preferably, it is at least one selected from the group of salt power.
[0015] 本発明の抗ストレス組成物は、 GABAと核酸関連化合物とを有効成分として含有す ることにより、より高い抗ストレス作用を発揮することができる。  [0015] The antistress composition of the present invention can exhibit a higher antistress effect by containing GABA and a nucleic acid-related compound as active ingredients.
[0016] また、本発明の飲食品は、前記抗ストレス組成物を含有することを特徴とするもので あり、本発明の抗ストレス組成物を日常的に摂取することが容易になり、精神的疲労 を効率よく抑制 ·軽減し、それに起因する健康障害の予防'改善効果が期待できる。 図面の簡単な説明  [0016] In addition, the food and drink of the present invention is characterized by containing the anti-stress composition, which makes it easy to ingest the anti-stress composition of the present invention on a daily basis. It is expected to effectively suppress and reduce fatigue, and to prevent and improve health problems caused by it. Brief Description of Drawings
[0017] [図 1]GABAと核酸関連化合物をそれぞれ単独で、あるいは組み合わせて摂取し、精 神的なストレスを負荷した場合における、唾液中のクロモグラニン A量に与える影響を 測定した結果を示す図である。 発明を実施するための最良の形態 [0017] [FIG. 1] A diagram showing the results of measuring the effect of saliva on the amount of chromogranin A in the case where GABA and a nucleic acid-related compound are ingested singly or in combination and are loaded with psychic stress. It is. BEST MODE FOR CARRYING OUT THE INVENTION
[0018] まず、本発明にお 、て「精神的なストレス」とは、緊張、不安、恐怖、孤独感等の心 理的状態のほか、人間関係や仕事等における心労を意味する。また、「抗ストレス作 用」とは、 1)上記のような精神的なストレスによる精神的疲労を抑制 ·軽減する、 2)精 神的疲労に起因する様々な健康障害、例えば、免疫機能の低下、ホルモンバランス の乱れ、情緒不安、睡眠障害等の予防'改善効果が期待できる、ことを意味する。  First, in the present invention, “mental stress” means mental state such as tension, anxiety, fear and loneliness, as well as mental work in human relations and work. “Anti-stress action” refers to 1) suppressing or reducing mental fatigue caused by mental stress as described above 2) various health disorders caused by mental fatigue, such as immune function It means that prevention, improvement effects such as decline, hormonal balance disturbance, emotional anxiety, and sleep disorders can be expected.
[0019] 本発明においては、上記の抗ストレス作用の指標として、唾液中のクロモグラニン A  [0019] In the present invention, chromogranin A in saliva is used as an index of the antistress action.
(以下「CgA」と略記する）を測定している。唾液中の CgA量は、肉体的なストレスにさ らされても変動しないが、精神的なストレスにさらされると上昇するため、精神的ストレ ス指標として利用できることが知られている（豊田中央研究所 R&Dレビュー  (Hereinafter abbreviated as “CgA”). It is known that the amount of CgA in saliva does not change even when exposed to physical stress, but increases when exposed to mental stress, so it can be used as a mental stress index (Toyota Central Research). R & D review
Vol. 34 No.3 (1999.9)参照）。したがって、精神的なストレスにさらされた際に、唾液 中の CgA量の上昇を抑制することは、該ストレスによる精神的疲労を抑制'軽減して いるものと考えられ、ひいては、それに起因する様々な健康障害の予防'改善効果が 期待できると考えられる。  Vol. 34 No. 3 (1999.9)). Therefore, suppressing an increase in the amount of CgA in saliva when exposed to mental stress is thought to suppress or reduce mental fatigue caused by the stress, and various factors resulting therefrom. It can be expected that the prevention and improvement of various health problems can be expected.
[0020] 本発明の抗ストレス組成物の有効成分の一つである GABAは、自然界に広く分布し ている非タンパク質アミノ酸の 1種であり、茶、野菜類、穀類等のほか、キムチなどの 発酵食品中に普通に含まれている成分である。また、生体内においては、グルタミン 酸が脱炭酸されて生成され、人体では特に脳内の黒質、大脳基底核、視床下部等 に高濃度に存在していることが知られており、生体への安全性が高い物質である。  [0020] GABA, which is one of the active ingredients of the anti-stress composition of the present invention, is one of non-protein amino acids widely distributed in nature, such as tea, vegetables, cereals, kimchi, etc. It is a component normally contained in fermented foods. Also, it is known that glutamate is produced by decarboxylation in the living body, and in the human body, it is known to be present in high concentrations especially in the substantia nigra, basal ganglia, hypothalamus, etc. It is a highly safe substance.
[0021] 本発明で使用される GABAは、食品に使用可能なものであれば特に制限されず、 例えば、グルタミン酸脱炭酸酵素ゃ該酵素を含有する植物や微生物を用いた方法 のほか、化学合成法や発芽玄米等の比較的 GABAを多く含有する原料から抽出する 方法などの公知の方法で得られたものを用いることができる。本発明においては、食 品としてのイメージや安全性、コスト等の点から、グルタミン酸脱炭酸酵素ゃ該酵素を 含有する植物や微生物を用いた方法によって得られた GABAが好ましく用いられる。  [0021] The GABA used in the present invention is not particularly limited as long as it can be used in foods. For example, glutamate decarboxylase is a method using plants or microorganisms containing the enzyme, as well as chemical synthesis. It is possible to use a product obtained by a known method such as a method or a method of extracting from a raw material containing a relatively large amount of GABA such as germinated brown rice. In the present invention, from the viewpoint of food image, safety, cost and the like, glutamic acid decarboxylase is preferably used GABA obtained by a method using a plant or microorganism containing the enzyme.
[0022] 例えば、乳酸菌を用いた発酵法としては、特開 2003— 70462号公報に記載された 方法などが好ましく例示できる。すなわち、グルタミン酸あるいはグルタミン酸ナトリウ ムと、ブドウ糖、酵母エキス、酢酸ナトリウム、硫酸マグネシウム等を含む培養液 (pH4. 0〜7.0)に、 Lactobacillus hilgardii K- 3 (ラクトバチルスヒルガルディー K- 3株、 FERM BP- 10487)の培養液を添加して、 20〜30°Cで 1〜3日間培養した後、得られた発酵 液 (該発酵液中の GABA含量は約 5質量％、固形分当りに換算すると GABAは約 70質 量 %)を加熱殺菌してカゝら濾過して濾液を得、この濾液を適宜濃縮してそのまま、ある いは更に乾燥粉末ィ匕することにより GABAを得ることができる。また、上記濾液をカラ ムクロマトグラフィー等の処理に供して GABAを更に精製してもよい。 [0022] For example, as a fermentation method using lactic acid bacteria, the method described in JP-A-2003-70462 can be preferably exemplified. That is, a culture solution (pH4.) Containing glutamic acid or sodium glutamate and glucose, yeast extract, sodium acetate, magnesium sulfate, etc. 0 to 7.0) was added with a culture solution of Lactobacillus hilgardii K-3 (Lactobacillus hilgardii K-3 strain, FERM BP-10487) and cultured at 20 to 30 ° C for 1 to 3 days. The fermented broth (GABA content in the fermented broth is about 5% by mass, and about 70% by mass GABA when converted to solid content) is sterilized by heating and filtered through a filter to obtain a filtrate. GABA can be obtained by concentrating as it is, or by further drying. In addition, GABA may be further purified by subjecting the filtrate to a treatment such as column chromatography.
[0023] なお、上記のようにして得られた発酵液中の GABA含有量の測定は、常法に従って 高速液体クロマトグラフィー (HPLC)やアミノ酸測定器等の分析機器を用いて行うこと ができる。例えば、試料を 0.2Nクェン酸ナトリウム緩衝液 (pH2.2)で適宜希釈（100倍 〜10,000倍)した後、固形物を遠心分離又は濾過により除去して測定試料を調製し、 下記条件で HPLCにより測定することができる。 [0023] The GABA content in the fermentation broth obtained as described above can be measured using analytical equipment such as high performance liquid chromatography (HPLC) and an amino acid measuring instrument according to a conventional method. For example, after appropriately diluting (100-fold to 10,000-fold) the sample with 0.2N sodium citrate buffer (pH 2.2), the solid is removed by centrifugation or filtration to prepare a measurement sample. Can be measured.
•装置:高速液体クロマトグラフ「LC- 10A」（商品名、株式会社島津製作所製） '分析用カラム:強酸性陽イオン交換榭脂カラム「Shim- pack Amino Na型」（商品名、 株式会社島津製作所製）  • Equipment: High-performance liquid chromatograph “LC-10A” (trade name, manufactured by Shimadzu Corporation) 'Analytical column: Strong acid cation exchange resin column “Shim-pack Amino Na type” (trade name, Shimadzu Corporation) (Manufactured)
•移動相緩衝液：「アミノ酸移動相キット Na型」（商品名、株式会社島津製作所製） ，移動相流量 : 0.4mL/分  • Mobile phase buffer: “Amino acid mobile phase kit Na type” (trade name, manufactured by Shimadzu Corporation), mobile phase flow rate: 0.4 mL / min
•反応相 1： 0.04%次亜塩素酸ナトリウム溶液 (pH 10のホウ酸—炭酸緩衝液 500mLに対 して次亜塩素酸 0.2mL)  • Reaction phase 1: 0.04% sodium hypochlorite solution (pH 10 boric acid-carbonate buffer 500mL vs hypochlorous acid 0.2mL)
•反応相 2 :「アミノ酸分析キット OPA試薬反応層」（商品名、株式会社島津製作所製） • Reaction Phase 2: “Amino Acid Analysis Kit OPA Reagent Reaction Layer” (trade name, manufactured by Shimadzu Corporation)
•流量：0.2ml/分 • Flow rate: 0.2ml / min
•温度： 60°C  • Temperature: 60 ° C
•検出:蛍光検出 (Ex  Detection: Fluorescence detection (Ex
348nm、 Em 450nm)  (348nm, Em 450nm)
[0024] 本発明の抗ストレス組成物のもう一つの有効成分である核酸関連化合物とは、核酸 塩基、ヌクレオシド、ヌクレオチド、核酸、あるいはそれらの誘導体 (オリゴヌクレオシド 、オリゴヌクレオチド、糖ヌクレオチド等)もしくは代謝産物等を意味するものであり、具 体的には、以下のような化合物が例示できる。  [0024] The nucleic acid-related compound that is another active ingredient of the anti-stress composition of the present invention is a nucleobase, nucleoside, nucleotide, nucleic acid, or a derivative thereof (oligonucleoside, oligonucleotide, sugar nucleotide, etc.) or metabolism. It means a product and the like, and specifically, the following compounds can be exemplified.
0核酸塩基:アデニン、グァニン、シトシン、チミン、ゥラシル等 ii)リボヌクレオシド：アデノシン、グアノシン、シチジン、ゥリジン、イノシン、キサントシン 等 0 Nucleobase: Adenine, guanine, cytosine, thymine, uracil, etc. ii) Ribonucleosides: adenosine, guanosine, cytidine, uridine, inosine, xanthosine, etc.
iii)デォキシリボヌクレオシド：デォキシアデノシン、デォキシグアノシン、デォキシシチ ジン、デォキシチミジン、デォキシゥリジン、デォキシイノシン等 iii) Deoxyribonucleosides: Deoxyadenosine, Deoxyguanosine, Deoxycytidine, Deoxythymidine, Deoxyuridine, Deoxyinosine, etc.
iv)リボヌクレオチド：アデニル酸 (AMP)、アデノシン 5'—二リン酸 (ADP)、アデノシン 5' 一三リン酸 (ATP)、グァ -ル酸（GMP)、グアノシン 5'—二リン酸（GDP)、グアノシン 5' 一三リン酸（GTP)、シチジル酸（CMP)、シチジン 5'—二リン酸（CDP)、シチジン 5'— 三リン酸（CTP)、ゥリジル酸（UMP)、ゥリジン 5'—二リン酸（UDP)、ゥリジン 5'—三リン 酸（UTP)、イノシン酸（IMP)、イノシン 5'—二リン酸（IDP)、イノシン 5'—三リン酸（ITP) 、キサンチル酸（XMP)等 iv) Ribonucleotides: adenylate (AMP), adenosine 5'-diphosphate (ADP), adenosine 5 'triphosphate (ATP), guarate (GMP), guanosine 5'-diphosphate (GDP) ), Guanosine 5 'triphosphate (GTP), cytidylic acid (CMP), cytidine 5'-diphosphate (CDP), cytidine 5'- triphosphate (CTP), uridylic acid (UMP), uridine 5' —Diphosphate (UDP), uridine 5′—triphosphate (UTP), inosine acid (IMP), inosine 5′—diphosphate (IDP), inosine 5′—triphosphate (ITP), xanthylic acid ( XMP) etc.
V)デォキシリボヌクレオチド：デォキシアデ-ル酸（dAMP)、デォキシアデノシン 5'— 二リン酸（dADP)、デォキシアデノシン 5' -三リン酸（dATP)、デォキシグァ -ル酸 (d GMP)、デォキシグアノシン 5'—二リン酸（dGDP)、デォキシグアノシン 5'—三リン酸（d GTP)、デォキシシチジル酸（dCMP)、デォキシシチジン 5'—二リン酸（dCDP)、デォ キシシチジン 5'—三リン酸（dCTP)、デォキシチミジル酸（dTMP)、デォキシチミジン 5' 二リン酸（dTDP)、デォキシチミジン 5'—三リン酸（dTTP)、デォキシゥリジル酸（dU MP)、デォキシゥリジン 5'—二リン酸（dUDP)、デォキシゥリジン 5'—三リン酸（dUTP) 、デォキシイノシン酸（dIMP)、デォキシイノシン 5'—二リン酸（dIDP)、デォキシイノシ ン 5'—三リン酸 (dITP) )等  V) Deoxyribonucleotides: Deoxyadelic acid (dAMP), Deoxyadenosine 5'—Diphosphate (dADP), Deoxyadenosine 5'-Triphosphate (dATP), Deoxygualuic acid (d GMP), deoxyguanosine 5'-diphosphate (dGDP), deoxyguanosine 5'-triphosphate (d GTP), deoxycytidylic acid (dCMP), deoxycytidine 5'-diphosphate (dCDP), de Oxycytidine 5'-triphosphate (dCTP), Deoxythymidylic acid (dTMP), Deoxythymidine 5 'Diphosphate (dTDP), Deoxythymidine 5'-Triphosphate (dTTP), Deoxyuridylic acid (dU MP), Deoxyuridine 5'- Diphosphate (dUDP), Deoxyuridine 5'-Triphosphate (dUTP), Deoxyinosinic acid (dIMP), Deoxyinosin 5'-Diphosphate (dIDP), Deoxyinosin 5'-Triphosphate (dITP)), etc.
vi)その他：キサンチン、ヒポキサンチン等 vi) Others: xanthine, hypoxanthine, etc.
vii)上記 0〜vi)に例示したィ匕合物の塩類 (ナトリウム塩、カリウム塩、カルシウム塩） viii)上記 0〜vii)に例示したィ匕合物の混合物 vii) Salts of the compounds exemplified in the above 0 to vi) (sodium salts, potassium salts, calcium salts) viii) Mixtures of compounds exemplified in the above 0 to vii)
本発明においては、上記核酸関連化合物の中でも、ゥラシル、ゥリジン、ゥリジル酸 (UMP)、ゥリジン 5'—二リン酸（UDP)、ゥリジン 5'—三リン酸（UTP)、アデニン、アデノ シン、アデ-ル酸 (AMP)、アデノシン 5'—二リン酸 (ADP)、アデノシン 5'—三リン酸 (A TP)、イノシン、イノシン酸 (IMP)、イノシン 5' -二リン酸（IDP)、イノシン 5' -三リン酸（I TP)、デォキシゥリジン、デォキシゥリジル酸（dUMP)、デォキシゥリジン 5'—二リン酸（ dUDP)、デォキシゥリジン 5'—三リン酸（dUTP)、デォキシアデノシン、デォキシアデ -ル酸（dAMP)、デォキシアデノシン 5' -二リン酸（dADP)、デォキシアデノシン 5' - 三リン酸（dATP)、デォキシイノシン、デォキシイノシン酸（dIMP)、デォキシイノシン 5' 一二リン酸（dIDP)、デォキシイノシン 5'—三リン酸（dITP)、キサンチン及びそれらの 塩類が好ましく例示できる、これらは単独で使用されても、 2種以上併用されてもよい 。また、本発明においては、上記核酸関連化合物を含む組成物として、サケ白子、煮 干し、カツォ節、しらす干し、干しシィタケ (あるいはそれらの抽出物）、酵母エキス、力 キ肉エキス、畜肉エキス、魚介類エキス、胚芽類等を用いることもできる。 In the present invention, among the above-mentioned nucleic acid-related compounds, uracil, uridine, uridylic acid (UMP), uridine 5′-diphosphate (UDP), uridine 5′-triphosphate (UTP), adenine, adenosine, adenine. -Auric acid (AMP), adenosine 5'-diphosphate (ADP), adenosine 5'-triphosphate (ATP), inosine, inosine acid (IMP), inosine 5'-diphosphate (IDP), inosine 5'-Triphosphate (ITP), Deoxyuridine, Deoxyuridylic acid (dUMP), Deoxyuridine 5'-Diphosphate (dUDP), Deoxyuridine 5'-Triphosphate (dUTP), Deoxyadenosine, Deoxyadede -Luric acid (dAMP), Deoxyadenosine 5 '-Diphosphate (dADP), Deoxyadenosine 5'-Triphosphate (dATP), Deoxyinosine, Deoxyinosinic acid (dIMP), Deoxyinosine 5 'Monodiphosphate (DIDP), deoxyinosine 5′-triphosphate (dITP), xanthine and salts thereof can be preferably exemplified, and these may be used alone or in combination of two or more. In the present invention, the composition containing the nucleic acid-related compound includes salmon roe, boiled and dried bonito, dried sardine, dried shiitake (or extracts thereof), yeast extract, hard meat extract, livestock meat extract, Seafood extracts, embryos and the like can also be used.
[0026] なお、核酸関連化合物の分析'定量は、 HPLCなどの公知の方法によって行うこと ができ、例えば、下記条件で HPLCにより行うことができる。  [0026] The analysis and quantification of the nucleic acid-related compound can be performed by a known method such as HPLC, and for example, can be performed by HPLC under the following conditions.
•装置:高速液体クロマトグラフ「LC- 10A」（商品名、株式会社島津製作所製） 'カフム：「smm- pacK  • Equipment: High-performance liquid chromatograph “LC-10A” (trade name, manufactured by Shimadzu Corporation) 'Kahum: “smm-pacK
VP-ODS (250 X 4.6mm)」（商品名、株式会社島津製作所製）  VP-ODS (250 X 4.6mm) "(trade name, manufactured by Shimadzu Corporation)
•移動相： A: 20mM酢酸アンモ-ゥム水溶液 (pH3.5)  • Mobile phase: A: 20 mM ammonium acetate aqueous solution (pH 3.5)
• B : 20mM酢酸アンモ-ゥム水溶液（pH3.5) /メタノール =90/10  • B: 20 mM ammonium acetate aqueous solution (pH 3.5) / methanol = 90/10
• 30% B (0— 5分）、 30— 100% B (5— 13分）、 100% B (13— 40分）  • 30% B (0—5 minutes), 30—100% B (5—13 minutes), 100% B (13—40 minutes)
，移動相流量 : 0.7mL/分  , Mobile phase flow rate: 0.7mL / min
•温度： 30°C  • Temperature: 30 ° C
'検出： UV260nm  'Detection: UV260nm
[0027] 本発明の抗ストレス組成物は、 GABAと上記核酸関連化合物を質量比で 1 : 0.0001 〜1： 0.1含有することが好ましぐ質量比で 1： 0.0003〜1： 0.05含有することがより好ま しぐ質量比で1 : 0.00045〜1 : 0.01で含有することがょり好ましぃ。 GABAと上記核酸 関連化合物の含有比が上記範囲外であると、より高い抗ストレス作用が得られなかつ たり、呈味が強くなつて飲食品に配合しに《なる場合もある。  [0027] The anti-stress composition of the present invention may contain GABA and the nucleic acid-related compound in a mass ratio of 1: 0.0001 to 1: 0.1, preferably in a mass ratio of 1: 0.0003 to 1: 0.05. It is more preferable to contain it at a mass ratio of 1: 0.00045 to 1: 0.01. If the content ratio of GABA and the nucleic acid-related compound is outside the above range, a higher anti-stress action may not be obtained, and the taste may be strong and may be added to food and drink.
[0028] 本発明の抗ストレス組成物は、上記基本的成分のほかに、テアニン、テオプロミン、 各種ハーブ（例えば、カモミール、ラベンダー、セントジヨーンズワート、パッションフラ ヮー、ホップ、ヴァレリアン)及びそのエキス等の抗ストレス作用を有する生理活性成 分や、他のアミノ酸類、ペプチド、賦形剤、糖類、オリゴ糖、乳化剤、酸味料、甘味料 、香料、ミネラル類、ビタミン類等を適宜含むことができる。また、その形態は特に制 限されず、例えば、溶液、粉末 '顆粒、錠剤、カプセル剤など、用途に応じて適宜選 択すればよい。 [0028] In addition to the above basic components, the antistress composition of the present invention includes theanine, theopromine, various herbs (for example, chamomile, lavender, St. John's wort, passion flower, hop, valerian) and its It contains physiologically active components having anti-stress action such as extracts, and other amino acids, peptides, excipients, sugars, oligosaccharides, emulsifiers, acidulants, sweeteners, flavors, minerals, vitamins, etc. Can do. The form is particularly limited. For example, a solution, a powder, a granule, a tablet, a capsule and the like may be appropriately selected depending on the application.
[0029] 本発明の抗ストレス組成物の有効摂取量は、精神的疲労の度合 ヽ、年齢、体重な どにより異なるため一概には決定できないが、通常、 1日当たり GABAとして 10〜3000 mg、核酸関連化合物として 0.001〜300mgであり、好ましくは、 1日当たり GABAとして 3 0〜1000mg、核酸関連化合物として 0.003〜100mgである（ただし、 GABAと核酸関連 化合物の摂取比率は質量比で 1： 0.0001〜1： 0.1とするのがよ!/、）。  [0029] The effective intake of the anti-stress composition of the present invention varies depending on the degree of mental fatigue, age, weight, etc., and thus cannot be determined unconditionally, but usually 10 to 3000 mg of GABA per day, nucleic acid The related compound is 0.001 to 300 mg, preferably 30 to 100 mg as GABA per day and 0.003 to 100 mg as the nucleic acid related compound (however, the intake ratio of GABA and the nucleic acid related compound is 1: 0.0001 to 1 by mass ratio) : It should be 0.1! /,).
[0030] 本発明の抗ストレス組成物は、例えば、清涼飲料、ゼリー飲料、乳飲料、乳酸菌飲 料、ココア飲料、コーヒー飲料、茶飲料、豆乳飲料、アルコール飲料 (例えば、ビール 、チューィ、カクテル、リキュール等）、スープ、乳製品（例えば、ヨーグルト、アイスタリ ーム類）、菓子（例えば、クッキー、ビスケット、ウエハース、ゼリー、プリン、チョコレート 、ガム、飴、ソフトキャンディー、キャラメル、錠菓等）、パン、麵類、サプリメント、レトル ト食品（例えば、カレー、おかゆ等）、冷凍食品、ドレッシング類等の各種飲食品に配 合することができる。  [0030] The antistress composition of the present invention includes, for example, soft drinks, jelly drinks, milk drinks, lactic acid bacteria drinks, cocoa drinks, coffee drinks, tea drinks, soy milk drinks, alcoholic drinks (for example, beer, chews, cocktails, Liqueur etc.), soup, dairy products (eg yogurt, ice cream), confectionery (eg cookies, biscuits, wafers, jelly, pudding, chocolate, gum, candy, soft candy, caramel, tablet confectionery, etc.), bread It can be combined with various foods and drinks such as potatoes, supplements, retort foods (eg, curry, porridge), frozen foods, and dressings.
[0031] 飲食品における本発明の抗ストレス組成物の配合量は、飲食品の形態によって異 なるため一概に決定できないが、 1回の喫食で上記有効摂取量の GABA及び核酸関 連化合物を摂取できるように配合することが好ま ヽ。  [0031] The amount of the antistress composition of the present invention in a food or drink cannot be determined unconditionally because it varies depending on the form of the food or drink, but the above effective intake of GABA and a nucleic acid-related compound are ingested in a single meal. It is preferable to mix it as possible.
[0032] また、各種飲食品における本発明の抗ストレス組成物の添加時期や添加方法は特 に制限されず、最初力も他の原料と一緒に添加してもよぐ製造工程の途中、あるい は後に添加してもよい。 [0032] In addition, the timing and method of addition of the antistress composition of the present invention in various foods and beverages are not particularly limited, and the initial power may be added together with other raw materials during the manufacturing process. May be added later.
[0033] 以下、実施例を挙げて本発明をより詳細に説明するが、本発明はこれらの実施例 により何ら限定されるものではな 、。  Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.
実施例 1  Example 1
[0034] 以下のサンプルを用いて、ヒトボランティア試験による唾液中の CgA量を指標とした 抗ストレス作用の測定を行った。なお、 GABAは純品（純度 100%)を用い、各サンプル における GABA含量は、核酸関連化合物の影響を見るために、 GABAを単独で摂取 した場合に抗ストレス作用が期待できる最低限の量に近い量とした。  [0034] Using the following samples, the anti-stress action was measured using the amount of CgA in saliva as an index in a human volunteer test. GABA is pure (100% purity), and the GABA content in each sample is the minimum that can be expected to have an anti-stress effect when GABA is ingested alone to see the effects of nucleic acid-related compounds. The amount was close.
•サンプル 1：純品 GABA (30mg) /水 lOOmL •サンプル 2：核酸関連化合物（ゥラシル： 0.014mg、 ATP： 0.014mg) Z水 lOOmL •サンプル 3：純品 GABA (30mg) +核酸関連化合物（ゥラシル： 0.014mg) Z水 lOOmL •サンプル 4:純品 GABA (30mg) +核酸関連化合物（ゥラシル： 0.014mg、 ATP : 0.014 mg) Z水 lOOmL • Sample 1: Pure GABA (30mg) / water lOOmL • Sample 2: Nucleic acid related compound (uracil: 0.014mg, ATP: 0.014mg) Z water lOOmL • Sample 3: Pure GABA (30mg) + Nucleic acid related compound (uracil: 0.014mg) Z water lOOmL • Sample 4: Pure product GABA (30mg) + Nucleic acid related compounds (uracil: 0.014mg, ATP: 0.014mg) Z water lOOmL
[0035] <試験方法 >  [0035] <Test method>
被験者 (4名）に、上記サンプル 1を摂取してもらい、 15分間の安静時間をとつた後、 内田クレペリン検査 (標準型）（株式会社日本'精神技術研究所製)を用いた暗算テ ストを 15分間実施することにより精神的なストレスを負荷した。 5分間の休憩をはさん で、再度 15分間のクレペリン暗算テストを実施した。そして、サンプル摂取直前 (0分） 、 1回目のクレペリン暗算テスト終了直後（サンプル摂取後 30分）、 2回目のクレペリン 暗算テスト終了直後（サンプル摂取後 50分)の計 3回にわたって、各被験者の唾液を 「サリベット」（商品名、 SARSTEDT社製)を用いて採取した。採取した唾液中に含まれ る CgAの測定は、「YK070ヒト'クロモグラニン A EIAキット」（商品名、矢内原研究所製 )を用いて行い、サンプル摂取直前（0分）の唾液中の CgA量を基準（100%)にして、サ ンプル摂取後の各時間における唾液中の CgA量の平均変化率 (％)を求めた。  Subject (4 persons) ingested sample 1 above, and after taking a rest time of 15 minutes, mental arithmetic test using Uchida-Kraepelin test (standard type) (manufactured by Japan Institute of Psychiatric Technology) Stressed mental stress by running for 15 minutes. After a 5-minute break, another 15-minute Kraepelin mental arithmetic test was performed. Each subject was tested three times, immediately before the sample intake (0 minutes), immediately after the end of the first Kraperin mental arithmetic test (30 minutes after the sample intake), and immediately after the end of the second Creperin mental arithmetic test (50 minutes after the sample intake). Saliva was collected using “Sullivet” (trade name, manufactured by SARSTEDT). CgA contained in the collected saliva is measured using the “YK070 human 'chromogranin A EIA kit” (trade name, manufactured by Yauchihara Laboratories), and the amount of CgA in the saliva immediately before sample intake (0 min) is measured. Based on the standard (100%), the average rate of change (%) in the amount of CgA in saliva at each time after sample intake was determined.
[0036] 上記サンプル 2〜4についても、上記サンプル 1と同様の試験を行って各被験者の 唾液を採取し、 CgA量を測定して、平均変化率 (％)を求めた。なお、これらの試験は 同じ被験者で行ったが、それぞれの試験結果に影響がでないように所定の期間（1週 間以上)を空けて行った。それらの結果を図 1に示す。  [0036] For Samples 2 to 4, the same test as in Sample 1 was performed to collect saliva from each subject, and the amount of CgA was measured to determine the average rate of change (%). Although these tests were performed on the same subjects, they were performed after a predetermined period (one week or longer) so that the results of each test were not affected. The results are shown in Fig. 1.
[0037] 図 1から、 GABAを単独（サンプル 1)で摂取した場合、及び核酸関連化合物を単独 ( サンプル 2)で摂取した場合にお!ヽては、精神的なストレスを負荷した際における唾液 中の CgA量の上昇がほとんど抑制されていないことが分かる。なお、サンプル 1を摂 取した場合に抗ストレス作用がほとんど見られなかったのは、この試験においては、 G ABA投与量を、 GABAの抗ストレス作用が期待できる最低限の量に近 、量としたため であると考えられる。  [0037] From FIG. 1, it can be seen that when GABA is ingested alone (sample 1) and when a nucleic acid-related compound is ingested alone (sample 2), saliva when mental stress is applied. It can be seen that the increase in the amount of CgA is hardly suppressed. In addition, in this study, the anti-stress effect was hardly observed when sample 1 was taken.In this study, the GABA dose was close to the minimum amount at which anti-stress effect of GABA can be expected. This is thought to be due to this.
[0038] 一方、抗ストレス作用が期待できる最低限の量の GABAと、核酸関連化合物とを一 緒に摂取した場合 (サンプル 3、 4)は、精神的なストレスを負荷した際における唾液中 の CgA量の上昇が効果的に抑制されていることが分かる。 [0039] 以上の結果から、 GABAと核酸関連化合物を一緒に摂取することにより、 GABAの 有する抗ストレス作用が増強されることが示唆された。 [0038] On the other hand, when the minimum amount of GABA that can be expected to have anti-stress action and a nucleic acid-related compound are ingested together (Samples 3 and 4), It can be seen that the increase in the amount of CgA is effectively suppressed. [0039] From the above results, it was suggested that the antistress action of GABA is enhanced by ingesting GABA and a nucleic acid-related compound together.
産業上の利用可能性  Industrial applicability
[0040] 本発明の抗ストレス組成物及びそれを含有する飲食品は、メンタルヘルスを改善す る健康食品等として利用でき、精神的なストレスにさらされる機会が多い社会人ゃ受 験生などに好適である。 [0040] The anti-stress composition of the present invention and food and drink containing the same can be used as health foods and the like that improve mental health, and can be used by students who are exposed to mental stress who are often exposed to mental stress. Is preferred.

Claims

請求の範囲 The scope of the claims
[1] Ύーァミノ酪酸と核酸関連化合物とを有効成分として含有することを特徴とする抗ス トレス組成物。  [1] An anti-stress composition characterized by containing an aminoaminobutyric acid and a nucleic acid-related compound as active ingredients.
[2] yーァミノ酪酸と核酸関連化合物を質量比で 1 : 0.0001〜1 : 0.1で含有する請求項 1 記載の抗ストレス組成物。  [2] The anti-stress composition according to claim 1, comprising y-aminobutyric acid and the nucleic acid-related compound in a mass ratio of 1: 0.0001 to 1: 0.1.
[3] 前記核酸関連化合物が、ゥラシル、ゥリジン、ゥリジル酸 (UMP)、ゥリジン 5' -二リン 酸（UDP)、ゥリジン 5'—三リン酸（UTP)、アデニン、アデノシン、アデ-ル酸 (AMP)、 アデノシン 5'—二リン酸 (ADP)、アデノシン 5'—三リン酸 (ATP)、イノシン、イノシン酸 (IMP)、イノシン 5' -二リン酸（IDP)、イノシン 5' -三リン酸（ITP)、デォキシゥリジン、 デォキシゥリジル酸（dUMP)、デォキシゥリジン 5'—二リン酸（dUDP)、デォキシゥリジ ン 5'—三リン酸（dUTP)、デォキシアデノシン、デォキシアデ-ル酸（dAMP)、デォキ シアデノシン 5' -二リン酸（dADP)、デォキシアデノシン 5' -三リン酸（dATP)、デォキ シイノシン、デォキシイノシン酸（dIMP)、デォキシイノシン 5'—二リン酸（dIDP)、デォ キシイノシン 5'—三リン酸 (dITP)、キサンチン及びそれらの塩類力もなる群力も選ば れた少なくとも 1種である請求項 1又は 2記載の抗ストレス組成物。  [3] The nucleic acid-related compounds include uracil, uridine, uridylic acid (UMP), uridine 5'-diphosphate (UDP), uridine 5'-triphosphate (UTP), adenine, adenosine, adenylate ( AMP), adenosine 5'-diphosphate (ADP), adenosine 5'-triphosphate (ATP), inosine, inosine acid (IMP), inosine 5'-diphosphate (IDP), inosine 5'-triphosphate Acid (ITP), Deoxyuridine, Deoxyuridylic acid (dUMP), Deoxyuridine 5'-Diphosphate (dUDP), Deoxyuridin 5'-Triphosphate (dUTP), Deoxyadenosine, Deoxyadeleic acid (dAMP), Deoxyuric acid Cyadenosine 5'-diphosphate (dADP), Deoxyadenosine 5'-Triphosphate (dATP), Deoxyinosine, Deoxyinosinic acid (dIMP), Deoxyinosine 5'-Diphosphate (dIDP), Deoxyinosine 5 '—Triphosphate (dITP), xanthine and their salt strength Anti-stress composition according to claim 1 or 2, wherein at least one group force was also chosen.
[4] 請求項 1〜3のいずれか一つに記載の抗ストレス組成物を含有することを特徴とす る飲食品。  [4] A food or drink comprising the anti-stress composition according to any one of claims 1 to 3.
PCT/JP2006/305418 2006-03-17 2006-03-17 Antistress composition and food and drink containing the same WO2007108071A1 (en)

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JP2010248161A (en) * 2009-04-20 2010-11-04 Ito En Ltd Anti-fatigue agent or physical strength improver containing uridine
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