JP2023012172A - Oral composition for stress reduction - Google Patents

Abstract

To provide a composition that effectively utilizes γ-aminobutyric acid, which is a stress reducing component.SOLUTION: An oral composition for stress reduction comprises (A) γ-aminobutyric acid as an active ingredient for stress reduction, the oral composition for stress reduction further comprising (B) chamomile and (C) two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen. Alternatively, an oral composition for stress reduction comprises (A) γ-aminobutyric acid, (B) camomile, and (C) two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen.SELECTED DRAWING: None

Description

There is an application for the application of Article 30, Paragraph 2 of the Patent Law. Month 4, issue name: Notification document of "Maintenite" food with functional claims by Toyo Shinyaku Co., Ltd., posting address: https://www. fld. caa. go. jp/caaks/cssc02/? recordSeq=42106090090200

The present invention relates to an oral composition characterized by containing γ-aminobutyric acid and chamomile.

Modern society is a stressful society, and accumulation of stress causes deterioration of immunity, obesity, hair loss, and the like. It is also said that stress can be one of the causes of atopic dermatitis, asthma, chronic hepatitis, angina pectoris, and diabetes.

As stress-relieving ingredients, for example, botanical grass (Patent Document 1), beef yellow, carrot, Chinese mugwort, licorice, and ginger (Patent Document 2) are known. However, in a stressful society, there is a strong demand for the development of combinations that improve the effect of stress reduction, rather than simply the components themselves that reduce stress, and sufficient research has not been conducted on such combinations.

JP-A-11-158077 JP 2009-126802 A

Therefore, the present inventors focused on γ-aminobutyric acid. An object of the present invention is to provide an oral composition that effectively utilizes γ-aminobutyric acid.

The present inventors have made intensive studies to solve the above problems, and surprisingly found that a combination of γ-aminobutyric acid and chamomile has an excellent stress-relieving effect. The present invention is an invention completed based on such findings.

The outline of the present invention is as follows.
[1] A stress-relieving oral composition containing (A) γ-aminobutyric acid as an active ingredient for stress-relieving, further comprising (B) chamomile and (C) theanine, ceramide, elastin, hyaluronic acid and collagen An oral composition for reducing stress, characterized by containing two or more selected substances.
[2] An oral composition comprising (A) γ-aminobutyric acid, (B) chamomile, and (C) two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen.
[3] A stress-reducing oral composition containing (A) γ-aminobutyric acid as an active ingredient for reducing stress, further comprising (B) chamomile and (C) theanine, ceramide, elastin, hyaluronic acid and collagen An oral composition for reducing stress, characterized by containing one or more selected substances.
[4] An oral composition comprising (A) γ-aminobutyric acid, (B) chamomile, and (C) one or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen.
[5] An oral composition comprising (A) γ-aminobutyric acid and (B) chamomile.
[6] (A) A stress-relieving oral composition containing γ-aminobutyric acid as a stress-relieving active ingredient, and further comprising (B) chamomile.

The composition of the present invention has an excellent stress-relieving effect.

The present invention will be described in detail below. In addition, the present invention is not limited to the following embodiments.

[A. γ-aminobutyric acid]
The composition of the present invention comprises gamma-aminobutyric acid (GABA) as an essential ingredient. γ-Aminobutyric acid is a kind of amino acid widely distributed in animals and plants, and is an inhibitory neurotransmitter present in the brain and marrow of mammals. As γ-aminobutyric acid, for example, synthetic products, those derived from plants such as tea, young barley leaves, germinated brown rice and barley, and those derived from fermentation by microorganisms such as lactic acid bacteria can be used. As the γ-aminobutyric acid derived from the fermented product, one obtained by fermenting a plant such as barley with a microorganism such as lactic acid bacteria may also be used. From the viewpoint of reducing stress, it is particularly preferable to use a plant such as barley fermented with a microorganism such as lactic acid bacteria.

The content ratio of γ-aminobutyric acid contained in the composition of the present invention is not particularly limited, and the content ratio can be appropriately set in a wide range according to various conditions such as the purpose, shape, and intended use. When the composition of the present invention is a solid formulation (powder, granule, granule, tablet, capsule, chewable, etc.), it is preferably 0.1 to 90% by mass, more preferably 1 to 80% by mass. A range of 5 to 65% by weight is particularly preferred. Further, when the composition of the present invention is a liquid agent (liquid, gel, paste, etc.), it is preferably 0.00001 to 30% by mass, more preferably 0.00005 to 20% by mass, and 0.0001 to 0.0001% by mass. 10% by weight is particularly preferred.

[B. chamomile]
The composition of the present invention has chamomile as an essential ingredient. Chamomile (Matricaria recutita L) is an annual plant belonging to the family Asteraceae, and is also called chamomile, chamomile, chamomile, Zelman, German chamomile, chamomile German, chamomile, and German chamomile. As the part of chamomile used, the whole may be used, or specific parts such as plant leaves, flowers, roots, stems, underground stems (rhizome, corm, tuber, bulb), seeds, buds, etc. may be used. Although there is no particular limitation, from the viewpoint of stress-relieving action, the above-ground parts (flowers, leaves, stems) are preferred, and flowers are particularly preferred. The method for treating chamomile is not particularly limited, but from the viewpoint of reducing stress, pulverized products, squeezed products, and extracts are preferred, and squeezed products and extracts are particularly preferred. An extraction solvent for preparing a chamomile extract is not particularly limited, but water, a water-soluble organic solvent, or a liquid mixture of water and a water-soluble organic solvent can be used. Examples of the water-soluble organic solvent include ethanol, methanol, etc. A mixed solvent of a plurality of solvents may be used as the extraction solvent, but from the viewpoint of stress reduction, chamomile flowers extracted with a hydrous ethanol solution are particularly preferred. . Moreover, the chamomile extract may be mixed with excipients such as dextrin and cyclodextrin as necessary.

The content ratio of chamomile is not particularly limited, and the content ratio can be appropriately set in a wide range according to various conditions such as purpose, shape, and use object. When the composition of the present invention is a solid formulation (powder, granule, granule, tablet, capsule, chewable, etc.), it is preferably 0.005 to 15% by mass, more preferably 0.01 to 10% by mass. is more preferred, and a range of 0.05 to 5% by mass is particularly preferred. Further, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 0.00001 to 15% by mass, more preferably 0.00005 to 10% by mass, and 0.0001 to 10% by mass. 5% by weight is particularly preferred.

[C. Theanine, ceramide, elastin, hyaluronic acid, collagen]
The composition of the present invention can contain (A) γ-aminobutyric acid, (B) chamomile, and (C) one or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen.

[Theanine]
Theanine is a kind of amino acid contained in tea, and is also known as γ-glutamylethylamide and γ-(ethylamido)L-glutamic acid. Theanine used in the present invention is not particularly limited, but L-theanine is particularly preferred. The method for producing theanine is not particularly limited, but those obtained by extraction from plants, those obtained by chemical synthesis, and those obtained by fermentation can be used. Theanine is commercially available as a reagent, food additive, etc., and it is particularly preferable to use the reagent.

The content ratio of theanine is not particularly limited, and the content ratio can be appropriately set in a wide range according to various conditions such as purpose, shape, and use object. When the composition of the present invention is a solid formulation (powder, granules, granules, tablets, capsules, chewables, etc.), it is preferably 0.005 to 30% by mass, more preferably 0.01 to 20% by mass. is more preferable, and a range of 0.05 to 10% by mass is particularly preferable. Further, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 0.00001 to 15% by mass, more preferably 0.00005 to 10% by mass, and 0.0001 to 10% by mass. 5% by weight is particularly preferred.

[Ceramide]
Ceramide is an amide bond between sphingosine and fatty acid. The ceramides used in the present invention are not particularly limited, but human ceramides such as ceramide 1, ceramide 2, and ceramide 3, animal-derived ceramides extracted from the brains and spinal cords of cows, horses, pigs, etc., wheat, Plant-derived ceramides extracted from rice, soybeans, spinach, corn, konjac, pineapple, etc. can be used. From the viewpoint of reducing stress, ceramide derived from rice is preferable, and ceramide derived from rice, which is the seed of rice, is particularly preferable. In addition, the ceramide used in the present invention may be a sugar ceramide, and specific examples thereof include those bound with monosaccharides such as galactosylceramide and glucosylceramide, and those bound with oligosaccharides. However, glucosylceramide is particularly preferred from the viewpoint of stress-relieving action. Solvents used for extracting ceramide used in the present invention include, for example, water; lower alcohols such as ethanol, methanol, isopropanol and butanol; lower esters such as ethyl acetate and methyl acetate; acetone; Solvents and the like are included. The temperature of the extraction solvent can be appropriately set between room temperature and the boiling point or below depending on the solvent used. Ethanol or water-containing ethanol is particularly preferable as the extraction solvent in the present invention, since the active ingredient can be efficiently extracted.

The content of ceramide is not particularly limited, and the content can be appropriately set in a wide range according to various conditions such as the purpose, shape, and intended use. When the composition of the present invention is a solid formulation (powder, granule, granule, tablet, capsule, chewable, etc.), it is preferably 0.005 to 15% by mass, more preferably 0.01 to 10% by mass. is more preferred, and a range of 0.05 to 5% by mass is particularly preferred. Further, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 0.00001 to 15% by mass, more preferably 0.00005 to 10% by mass, and 0.0001 to 10% by mass. 5% by weight is particularly preferred.

[Elastin]
Elastin is a major elastic protein that exists together with collagen in mammals, birds, fish, etc., particularly mammalian aorta, ligamentum necrosum, ligamentum flavum, lungs, skin, uterus, elastic cartilage, etc. Also called fiber. Elastin used in the present invention includes not only water-soluble elastin but also hydrolyzed elastin, α-elastin, κ-elastin and elastin peptides. Elastin used in the present invention is not particularly limited, and hydrolyzed skins and connective tissues of fish such as cod, mackerel, salmon, herring, sea bream, tuna, and sardines can be used. In the present invention, elastin obtained by hydrolyzing cod skin is particularly preferred from the viewpoint of stress-relieving action.

The content ratio of elastin is not particularly limited, and the content ratio can be appropriately set in a wide range according to various conditions such as purpose, shape, and use object. When the composition of the present invention is a solid formulation (powder, granule, granule, tablet, capsule, chewable, etc.), it is preferably 0.005 to 15% by mass, more preferably 0.01 to 10% by mass. is more preferred, and a range of 0.05 to 5% by mass is particularly preferred. Further, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 0.00001 to 15% by mass, more preferably 0.00005 to 10% by mass, and 0.0001 to 10% by mass. 5% by weight is particularly preferred.

[hyaluronic acid]
Hyaluronic acid is a type of mucopolysaccharide present in the skin, joints, vitreous body of the eye, etc. of humans and vertebrates, and is also called hyaluronan. Although the hyaluronic acid used in the present invention is not particularly limited, hyaluronic acid derived from chicken combs, microbially derived hyaluronic acid, synthetic products, and hyaluronic acid hydrolyzed using enzymes can be used. Hyaluronic acid in the present invention is a concept that includes salts of hyaluronic acid such as sodium hyaluronate and potassium hyaluronate, and hydrolyzed hyaluronic acid and other degradation products obtained by reducing the molecular weight of hyaluronic acid. As the hyaluronic acid of the present invention, sodium hyaluronate is particularly preferred from the viewpoint of stress-relieving action. Moreover, the molecular weight of the hyaluronic acid used in the present invention varies depending on the number and types of repeating units, and is not limited. Hyaluronic acid having a weight average molecular weight of several hundred to several million may be used, or hydrolyzed hyaluronic acid having an average molecular weight of 10,000 or less may be used.

The content ratio of hyaluronic acid is not particularly limited, and the content ratio can be appropriately set in a wide range according to various conditions such as purpose, shape, and use object. When the composition of the present invention is a solid formulation (powder, granule, granule, tablet, capsule, chewable, etc.), it is preferably 0.005 to 15% by mass, more preferably 0.01 to 10% by mass. is more preferable, and a range of 0.05 to 5% by mass is particularly preferable. Further, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 0.00001 to 15% by mass, more preferably 0.00005 to 10% by mass, and 0.0001 to 10% by mass. 5% by weight is particularly preferred.

[collagen]
Collagen is a kind of protein that mainly constitutes the dermis, ligaments, tendons, bones, cartilage, etc. of vertebrates, and is a major component of the extracellular matrix of multicellular animals. Collagen used in the present invention is not particularly limited, but includes animal-derived collagen, synthetic collagen, collagen protein, hydrolyzed collagen (collagen peptide) obtained by hydrolyzing collagen protein, and telopeptide obtained by treating collagen molecules with protease. Partially removed atelocollagen can be used. As the collagen of the present invention, hydrolyzed collagen is particularly preferable from the viewpoint of stress reduction action. The average molecular weight (weight average molecular weight) of the collagen of the present invention is not particularly limited. For example, the lower limit of the average molecular weight is preferably 100 or more, more preferably 300 or more, and particularly preferably 500 or more. The upper limit of the molecular weight is preferably 100,000 or less, more preferably 80,000 or less, and particularly preferably 50,000 or less.

The content ratio of collagen is not particularly limited, and the content ratio can be appropriately set in a wide range according to various conditions such as purpose, shape, and use object. When the composition of the present invention is a solid formulation (powder, granule, granule, tablet, capsule, chewable, etc.), it is preferably 0.005 to 15% by mass, more preferably 0.01 to 10% by mass. is more preferred, and a range of 0.05 to 5% by mass is particularly preferred. Further, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 0.00001 to 15% by mass, more preferably 0.00005 to 10% by mass, and 0.0001 to 10% by mass. 5% by weight is particularly preferred.

In the composition of the present invention, (C) one or more components selected from theanine, ceramide, elastin, hyaluronic acid and collagen may contain one or more of these from the viewpoint of reducing stress. Preferably, 2 or more are more preferably contained, 3 or more are particularly preferable, 4 or more are particularly preferable, and 5 are most preferable.

In the composition of the present invention, the content ratio of (C) one or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen is not particularly limited, and can be applied to various conditions such as purpose, shape, and intended use. Accordingly, the content ratio can be appropriately set in a wide range. When the composition of the present invention is a solid formulation (powder, granule, granule, tablet, capsule, chewable, etc.), it is preferably 0.005 to 60% by mass, more preferably 0.01 to 40% by mass. is more preferable, and a range of 0.05 to 30% by mass is particularly preferable. Further, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 0.00001 to 60% by mass, more preferably 0.00005 to 40% by mass, and 0.0001 to 0.0001% by mass. 20% by weight is particularly preferred. The content ratio of (C) in the case of containing two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen means the total amount of each component.

In the composition of the present invention, the total content of one or more selected from (A) γ-aminobutyric acid, (B) chamomile, (C) theanine, ceramide, elastin, hyaluronic acid and collagen is not particularly limited. However, the content ratio can be appropriately set in a wide range according to various conditions such as purpose, shape, and use object. When the composition of the present invention is a solid (powder, granule, tablet, capsule, chewable, etc.), it is preferably 0.1 to 99% by mass, more preferably 1 to 85% by mass. Preferably, 10 to 80% by mass is particularly preferred. Further, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 0.00001 to 70% by mass, more preferably 0.00005 to 60% by mass, and 0.0001 to 0.0001% by mass. 50% by weight is particularly preferred. The content ratio of (C) in the case of containing two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen means the total amount of each component.

In the present invention, the mass ratio of (A) to the total mass of one or more selected from (A) γ-aminobutyric acid, (B) chamomile, (C) theanine, ceramide, elastin, hyaluronic acid and collagen is particularly limited. However, from the viewpoint of reducing stress, (A) is preferably 0.0001 to 0.9 times the total mass of (A) to (C), more preferably 0.0005 to 0.8 times, and 0 0.001 to 0.5 times is particularly preferred. The mass of (C) in the case of containing two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen means the total amount of each component.

In the present invention, the mass ratio of (B) to the total mass of one or more selected from (A) γ-aminobutyric acid, (B) chamomile, (C) theanine, ceramide, elastin, hyaluronic acid and collagen is particularly limited. However, from the viewpoint of reducing stress, (B) is preferably 0.0001 to 0.9 times the total mass of (A) to (C), more preferably 0.0005 to 0.8 times, and 0 0.001 to 0.5 times is particularly preferred. In addition, the mass of (C) when containing two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen means the total amount of each component.

In the present invention, the mass ratio of (C) to the total mass of one or more selected from (A) γ-aminobutyric acid, (B) chamomile, (C) theanine, ceramide, elastin, hyaluronic acid and collagen is particularly limited. However, from the viewpoint of stress reduction effect, (C) is preferably 0.0001 to 0.9 times the total mass of (A) to (C), more preferably 0.0005 to 0.8 times, and 0 0.001 to 0.5 times is particularly preferred. In addition, the mass of (C) when containing two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen means the total amount of each component.

In the composition of the present invention, the ratio of the total mass of (C) one or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen to the total mass of (A) γ-aminobutyric acid and (B) chamomile is not particularly limited, but from the viewpoint of stress reduction action, (C) is preferably 0.00001 to 10 times the total mass of (A) and (B), more preferably 0.00005 to 5 times, and 0 0.0001 to 1 times is particularly preferred. In addition, the mass of (C) when containing two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen means the total amount of each component.

In the composition of the present invention, the mass ratio of (B) chamomile to (A) γ-aminobutyric acid is not particularly limited. 000001 to 10 times is preferable, 0.000005 to 5 times is more preferable, and 0.00001 to 1 times is particularly preferable.

In the composition of the present invention, the ratio of the total mass of (C) one or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen to the mass of (A) γ-aminobutyric acid is not particularly limited. From the viewpoint of action, (C) is preferably 0.00001 to 10 times, more preferably 0.00005 to 5 times, and particularly preferably 0.0001 to 1 times that of (A). In addition, the mass of (C) when containing two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen means the total amount of each component.

In the composition of the present invention, the ratio of the total mass of one or more selected from (C) theanine, ceramide, elastin, hyaluronic acid and collagen to the mass of (B) chamomile is not particularly limited, but from the viewpoint of stress reduction effect Therefore, (C) is preferably 0.01 to 1000 times, more preferably 0.05 to 500 times, and particularly preferably 0.1 to 200 times that of (B). In addition, the mass of (C) when containing two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen means the total amount of each component.

The daily usage amount of the composition of the present invention is not particularly limited. Based on the body weight of the user, 0.1 to 1000 mg/kg is preferable, 0.5 to 500 mg/kg is more preferable, and 1 to 100 mg/kg is particularly preferable from the viewpoint of reducing stress. When the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 100 to 40,000 mg/kg, more preferably 300 to 30,000 mg/kg, based on the body weight of the user. 500 to 20,000 mg/kg is particularly preferred from the viewpoint of stress-relieving action.

The amount of the composition of the present invention used at one time is not particularly limited. Based on the body weight of the user, 0.1 to 1000 mg/kg is preferable, 0.5 to 500 mg/kg is more preferable, and 1 to 100 mg/kg is particularly preferable from the viewpoint of reducing stress. When the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 100 to 40,000 mg/kg, more preferably 300 to 30,000 mg/kg, based on the body weight of the user. 500 to 20,000 mg/kg is particularly preferred from the viewpoint of stress-relieving action.

The daily usage amount of the composition of the present invention is not particularly limited. 0.01 to 10 g is preferable, 0.1 to 5 g is more preferable, and 0.2 to 3 g is particularly preferable from the viewpoint of stress reduction action. In addition, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 10 to 1000 g, more preferably 30 to 750 g, and particularly 50 to 500 g from the viewpoint of reducing stress. preferable.

The amount of the composition of the present invention used at one time is not particularly limited. 0.01 to 10 g is preferable, 0.1 to 5 g is more preferable, and 0.2 to 3 g is particularly preferable from the viewpoint of stress reducing action. In addition, when the composition of the present invention is a liquid (liquid, gel, paste, etc.), it is preferably 10 to 1000 g, more preferably 30 to 750 g, and particularly 50 to 500 g from the viewpoint of reducing stress. preferable.

The composition of the present invention may contain only one or more selected from (A) γ-aminobutyric acid, (B) chamomile, (C) theanine, ceramide, elastin, hyaluronic acid and collagen. However, in addition to the above components, other components may be contained. Other ingredients include, for example, various excipients, binders, lubricants, stabilizers, diluents, bulking agents, thickeners, emulsifiers, colorants, fragrances, additives, cosmetic raw materials, pharmaceutical raw materials, etc. can be mentioned. The content of other components can be appropriately selected according to the usage form of the composition of the present invention.

The composition of the present invention can be used in various forms for the purpose of obtaining a stress-relieving effect.

The composition of the present invention is not particularly limited as long as it can be distinguished from other products as a product in that it can be used for stress-relieving action. The scope of the present invention includes a product that indicates that it has a stress-relieving function in any of , manuals, and advertisements. For example, pharmaceuticals (including quasi-drugs), so-called health foods such as foods for specified health uses, foods with nutrient function claims, functional foods whose efficacy has been approved by designated organizations, feeds, etc. can be mentioned. In so-called health foods, there are many types of foods that can be used to relieve stress, relieve temporary stress, alleviate temporary mental stress caused by work or study, and relieve temporary stress (irritation) caused by work, etc. )”, “Useful for reducing temporary stress”, etc. can be exemplified.

The form of the composition of the present invention is not particularly limited, and can be any form. For example, forms suitable for oral compositions, specifically powders, granules, granules, tablets, liquids, gels, pastes, capsules such as hard capsules and soft capsules, caplets, chewables, etc. Various excipients, binders, lubricants, stabilizers, diluents, extenders, thickeners, gelling agents, emulsifiers, colorants, perfumes, Sweeteners, additives and the like may be included. The composition of the present invention is preferably in the form of granules, tablets, liquids, gels, capsules or chewables, and more preferably in the form of granules, tablets or capsules, from the viewpoint of reducing stress. Here, "granular" refers to a composition obtained by granulating powder, and "gel" refers to a composition containing water and a gelling agent and having viscosity or elasticity.

The packaging form of the composition of the present invention is not particularly limited, and can be appropriately selected depending on the dosage form. Examples include blister packs such as PTP; strip packaging; heat sealing; aluminum pouches; packaging; glass containers such as vials; and plastic containers such as ampoules.

The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these Examples, and the present invention can take various aspects as long as the problems of the present invention can be solved. .

(Test substance)
As test substances, γ-aminobutyric acid (barley fermented with lactic acid bacteria), chamomile extract (chamomile flower extracted with 50% aqueous ethanol solution), rice-derived glucosylceramide (rice extracted with ethanol) , elastin (hydrolyzed cod skin), sodium hyaluronate (average molecular weight: 1,200,000), and hydrolyzed collagen (average molecular weight: 2,000) were used (all commercially available products). As the theanine, a reagent (synthetic product of L-theanine) was used.

(Test method)
Rat adrenal pheochromocytoma cells (PC12, JCRB cell bank) were cultured in 10% by volume FBS-RPMI 1640 medium and seeded at 100 μL/well in a collagen-coated 96-well plate at 4×10 4 cells/well. , 37°C, 5 vol% CO2 incubator for 24 hours.

After culturing for 24 hours, 100 μL/well of the test substance-containing medium was added to the medium already in the wells, and cultured at 37° C. in a 5% by volume CO 2 incubator for 24 hours. A 10% by volume FBS-RPMI 1640 medium was used as the medium. Tables 1 and 2 show the concentration (μg/mL) of each component in the test substance. In Examples 1-10 and Comparative Examples 1-9, the total concentration of the test substances in the medium was 2.5 μg/mL.

After culturing for 24 hours, hydrogen peroxide was diluted to 2.2 mM with 10% by volume FBS-RPMI 1640 medium, and 20 μL/well was added to the medium already contained in the wells (final concentration 200 μM). It was cultured for 2 hours in a 37° C., 5 vol % CO2 incubator.

After removing the medium from each well, RNA was recovered using CellAmp Direct RNA Prep Kit for RT-PCR (manufactured by Takara). Quantitative real-time PCR was performed on the obtained RNA using One Step TB Green (registered trademark) PrimeScript RT-PCR Kit II (manufactured by Takara). HO-1 gene (Hmox1) primer (manufactured by QIAGEN, trade name: Rn_Hmox1_1_SG QuantiTectPrimer Assay (QT00175994)) was used to measure the gene expression level of HO-1 gene. As an endogenous control, the GAPDH gene expression level was measured using a GAPDH primer (manufactured by QIAGEN, trade name: Rn_Gapd_1_SG QuantiTect Primer Assay (QT00199633)). The relative value of the HO-1 gene expression level was calculated when the expression level of the group to which no test substance was administered (control) was set to 1.

Tables 1 and 2 show the results.

One of the causes of feeling mental stress is thought to be that oxidative stress and mitochondrial disorders are induced by various stresses, and neuronal disorders are induced. Heme Oxygenase 1 (hereinafter also referred to as "HO-1") is known to have a mitochondria-protecting effect under oxidative stress. From this, it is considered that compositions that enhance gene expression of HO-1 are useful for improving resistance to various stresses.

An increase in the HO-1 gene amount was not confirmed for each component of Comparative Examples 1 and 2 compared to the control, but surprisingly, Example 1 in which (A) γ-aminobutyric acid was combined with (B) chamomile , an increase in the expression level of HO-1 was confirmed. In addition, when (A) γ-aminobutyric acid and (C) theanine or rice-derived glucosylceramide were combined as in Comparative Examples 8 and 9, no increase in the HO-1 gene amount was confirmed. A) A combination of γ-aminobutyric acid and (B) chamomile was found to be particularly effective in increasing the HO-1 gene, and such a combination composition is effective in reducing stress. I found out.

As can be seen from Comparative Examples 1 to 3 and 8, HO in (A) γ-aminobutyric acid, (B) chamomile and (C) theanine alone or in combination of (A) γ-aminobutyric acid and (C) theanine Although no increase in HO-1 gene dosage was observed, Example 2, which combined these three components, showed a superior increase in HO-1 gene dosage. In particular, the increase in HO-1 gene dosage compared to Example 1 is surprising. Further, as can be seen from Comparative Examples 1, 2, 4 and 9, (A) γ-aminobutyric acid, (B) chamomile and (C) rice-derived glucosylceramide alone or (A) γ-aminobutyric acid and (C) ) Although no increase in HO-1 gene level was confirmed in the combination of rice-derived glucosylceramide, Example 3, in which these three components were combined, showed an excellent increase in HO-1 gene level. In particular, the increase in HO-1 gene dosage compared to Example 1 is surprising. Furthermore, as can be seen from Comparative Examples 1, 2, and 5, (A) γ-aminobutyric acid, (B) chamomile, and (C) elastin alone did not increase the HO-1 gene amount, but these three The combination of ingredients, Example 4, showed excellent HO-1 gene dosage increase. In particular, the increase in HO-1 gene dosage compared to Example 1 is surprising.

As can be seen from Comparative Examples 1 to 4, 8, and 9, (A) γ-aminobutyric acid, (B) chamomile and (C) theanine, rice-derived glucosylceramide alone, or (A) γ-aminobutyric acid and ( C) Theanine, or the combination of (A) γ-aminobutyric acid and (C) rice-derived glucosylceramide did not increase the amount of HO-1 gene, but Example 5, in which these four components were combined, was excellent. showed an increase in HO-1 gene dosage. In particular, the increase in HO-1 gene dosage compared to Examples 1-4 is surprising. In addition, as can be seen from Comparative Examples 1, 2, 4, 5 and 9, (A) γ-aminobutyric acid, (B) chamomile and (C) rice-derived glucosylceramide and elastin alone, or (A) γ- Although no increase in HO-1 gene level was confirmed in the combination of aminobutyric acid and (C) rice-derived glucosylceramide, Example 6, in which these four components were combined, showed an excellent increase in HO-1 gene level. . In particular, it is surprising that the HO-1 gene amount was increased compared to Examples 1-4.

As can be seen from Comparative Examples 1 to 5, 8, and 9, (A) γ-aminobutyric acid, (B) chamomile and (C) theanine, rice-derived glucosylceramide, and elastin, or (A) γ-aminobutyric acid and (C) theanine, or (A) γ-aminobutyric acid and (C) rice-derived glucosylceramide, an increase in the HO-1 gene amount was not confirmed. , showed a superior increase in HO-1 gene dosage. In particular, the increase in HO-1 gene dosage compared to Examples 1-6 is surprising. In addition, as can be seen from Comparative Examples 1, 2, 4 to 6, and 9, (A) γ-aminobutyric acid, (B) chamomile and (C) rice-derived glucosylceramide, elastin, and sodium hyaluronate each alone, or ( Although no increase in HO-1 gene level was confirmed in the combination of A) γ-aminobutyric acid and (C) rice-derived glucosylceramide, Example 8, in which these five components were combined, showed excellent HO-1 gene level. showed an increase. In particular, the increase in HO-1 gene dosage compared to Examples 1-6 is surprising.

As can be seen from Comparative Examples 1, 2, 4 to 7, and 9, (A) γ-aminobutyric acid, (B) chamomile and (C) rice-derived glucosylceramide, elastin, sodium hyaluronate, and sodium hydrolyzate each alone, or , (A) γ-aminobutyric acid and (C) rice-derived glucosylceramide did not increase the amount of the HO-1 gene, but Example 9, which combines these six components, has an excellent HO-1 gene showed an increase in volume. In particular, the increase in HO-1 gene dosage compared to Examples 1-8 is surprising.

As can be seen from Comparative Examples 1 to 9, (A) γ-aminobutyric acid, (B) chamomile and (C) theanine, rice-derived glucosylceramide, elastin, sodium hyaluronate, sodium hydrolyzate, or (A) No increase in HO-1 gene level was confirmed in the combination of γ-aminobutyric acid and (C) theanine, or (A) γ-aminobutyric acid and (C) rice-derived glucosylceramide, but these seven components were combined. Example 10 showed excellent HO-1 gene dosage increase. In particular, the increase in HO-1 gene dosage compared to Examples 1-9 is surprising.

As described above, the composition containing (A) γ-aminobutyric acid and (B) chamomile of the present invention has a stress-relieving effect, and (C) theanine, rice-derived glucosylceramide, elastin, sodium hyaluronate, and By further combining one or more, preferably two or more, more preferably three or more, particularly preferably four or more, and most preferably five selected from degraded collagen, an excellent stress-reducing effect can be achieved. I found out.

(Manufacturing example)
Production examples of the present invention are shown below. Note that % in Tables 3 to 9 represents % by mass.

[Production Example 1-4: Granules]
After mixing the raw materials as shown in Table 3, fluid bed granulation was performed using a granulator to produce granules described in Production Examples 1-4. The granules described in Production Examples 1-4 may be ingested at a dose of 3 g per day, and may be ingested after being dissolved in a solvent such as 100 ml of water, or may be ingested without being dissolved. All of the granules of Production Examples 1-4 are effective in reducing stress.

[Production Example 5-8: Tablet]
After mixing the raw materials as shown in Table 4, tableting was performed using a rotary tableting machine to produce tablets of Production Examples 5-8. Tablets were manufactured to have a tablet diameter of 8 mmφ, a tablet thickness of 4.5 mm, a weight of 300 mg, and a hardness of 5 kgf or more. One or two tablets described in Production Examples 5-8 may be ingested per day, and can be ingested with 100 ml of water or the like. All of the tablets of Production Examples 5-8 are effective in reducing stress.

[Production Example 9-34: Hard Capsule]
Hard capsules were produced by mixing raw materials according to Tables 5-9 and encapsulating with a coating containing gelatin or hydroxypropylcellulose. The hard capsule was manufactured with 300 mg per tablet (content: 230 mg, film: 70 mg). One or two tablets may be taken per day, and can be taken with 100 ml of water or the like. In addition, any of the hard capsules of Production Examples 9-34 are effective in reducing stress.

INDUSTRIAL APPLICABILITY The composition of the present invention is highly industrially useful because it has an excellent stress-relieving action.

Claims (4)

(A) A stress-reducing oral composition containing γ-aminobutyric acid as an active ingredient for stress reduction, further selected from (B) chamomile and (C) theanine, ceramide, elastin, hyaluronic acid and collagen An oral composition for stress relief, characterized by containing two or more kinds. An oral composition comprising (A) γ-aminobutyric acid, (B) chamomile, and (C) two or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen. (A) A stress-reducing oral composition containing γ-aminobutyric acid as an active ingredient for stress reduction, further selected from (B) chamomile and (C) theanine, ceramide, elastin, hyaluronic acid and collagen An oral composition for stress relief, characterized by containing one or more. An oral composition comprising (A) γ-aminobutyric acid, (B) chamomile, and (C) one or more selected from theanine, ceramide, elastin, hyaluronic acid and collagen.