CD39 expression promoter

Abstract

To provide an agent suitable for promoting expression of CD39 or the like.SOLUTION: An agent contains, for example, at least one kind of a component selected from a carnosic acid, β-glucan, an extract from Lamiaceae plants, and a Ganoderma lucidum extract.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an agent useful for promoting the expression (production) of CD39, etc.

Background Art

[0002] CD39 is a membrane protein also known as ectonucleoside triphosphate diphosphohydrolase 1, EctoATPDase, etc., and is an ectonucleotidase that hydrolyzes ATP and adenosine diphosphate (ADP) to AMP.

[0003] Such CD39 (CD39 molecule) is expressed (present) in B cells, T cells, natural killer cells, dendritic cells, vascular endothelial cells, etc., and is considered to be involved in functions such as suppression of inflammatory reactions and activation of platelet functions by decomposing extracellular ATP and ADP.

[0004] Therefore, by promoting the expression of CD39, it is expected to enhance or efficiently exert such functions, and the search for components that promote the expression of CD39 is underway. For example, Patent Document 1 discloses a CD39 expression promoter containing a dulmagic extract.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] An object of the present invention is to provide an agent, etc. useful for promoting (increasing) the expression (production) of CD39, etc.

Means for Solving the Problems

[0007] As a result of intensive studies to achieve the above object, the present inventors have found that specific components are effective (useful) for the expression (production) of CD39, and have thus completed the present invention.

[0008] That is, the present invention relates to the following inventions and the like. [1] An agent or composition for promoting CD39 expression, comprising carnosine. [2] An agent or composition for promoting CD39 expression, comprising an extract of a Lamiaceae plant (particularly, an extract of a Lamiaceae plant containing carnosine). [3] An agent or composition for promoting CD39 expression, comprising β-glucan (for example, β-glucan derived from fermented Ganoderma lucidum). [4] An agent or composition for promoting CD39 expression, comprising a Ganoderma lucidum extract (particularly, a fermented Ganoderma lucidum extract). [5] An agent or composition for promoting CD39 expression, comprising carnosine and a Ganoderma lucidum extract (particularly, a fermented Ganoderma lucidum extract). [6] An agent or composition for promoting CD39 expression, comprising an extract of a Lamiaceae plant (particularly, an extract of a Lamiaceae plant containing carnosine) and a Ganoderma lucidum extract (particularly, a fermented Ganoderma lucidum extract). [7] An agent or composition comprising at least one selected from carnosine, an extract of a Lamiaceae plant (particularly, an extract of a Lamiaceae plant containing carnosine), β-glucan (for example, β-glucan derived from fermented Ganoderma lucidum), and a Ganoderma lucidum extract (for example, a fermented Ganoderma lucidum extract), and used for at least one use selected from the following (1) to (3). (1) Suppression or improvement of inflammation (for example, suppression of skin inflammation) (2) Maintenance of homeostasis (for example, maintenance of skin homeostasis) (3) Suppression of external stimulus response (calming) (for example, suppression of external stimulus response in the skin) [8] An extract of a Lamiaceae plant, including rosemary extract, the agent or composition described in [2], [6] or [7]. [9] An extract of a Lamiaceae plant (e.g., rosemary extract) containing an extract of at least one solvent selected from water, alcohols (e.g., lower alcohols such as ethanol), and mixed solvents thereof, the agent or composition described in [2], [6], [7], [8].

[10] An extract of Ganoderma lucidum (especially, fermented Ganoderma lucidum extract) containing an extract of at least one solvent selected from water, alcohols (e.g., lower alcohols such as ethanol), and mixed solvents thereof, the agent or composition described in any one of [4] to [9].

[11] Containing at least carnosine and an extract of Ganoderma lucidum (especially, fermented Ganoderma lucidum extract), The ratio of carnosine to the extract of Ganoderma lucidum (especially, fermented Ganoderma lucidum extract) is 0.01 to 1000 parts by mass (e.g., 0.5 to 500 parts by mass, 1 to 300 parts by mass, 20 to 40 parts by mass) of the extract of Ganoderma lucidum (especially, fermented Ganoderma lucidum extract) per 1 part by mass of carnosine, the agent or composition described in any one of [5] to

[10] .

[12] Containing at least an extract of a Lamiaceae plant (e.g., rosemary extract) and an extract of Ganoderma lucidum (especially, fermented Ganoderma lucidum extract), The ratio of the extract of a Lamiaceae plant (e.g., rosemary extract) to the extract of Ganoderma lucidum (especially, fermented Ganoderma lucidum extract) is 0.1 to 3000 parts by mass (e.g., 1 to 1000 parts by mass, 5 to 500 parts by mass, 30 to 150 parts by mass) of the extract of Ganoderma lucidum (especially, fermented Ganoderma lucidum extract) per 1 part by mass of the extract of a Lamiaceae plant (e.g., rosemary extract), the agent or composition described in any one of [6] to

[11] .

[13] The agent or composition described in any one of [1] to

[12] , which is a cosmetic (composition for use). [Effect of the Invention]

[0009] According to the present invention, it is possible to provide an agent or the like useful for promoting (increasing) the expression of CD39 (CD39 molecule).

Mode for Carrying Out the Invention

[0010] [Agent] The present invention provides an agent containing (including as an active ingredient) at least one component selected from carnosine, β-glucan, an extract of a Lamiaceae plant, and an extract of Ganoderma lucidum (sometimes referred to as component A, etc.).

[0011] (Carnosine) In an agent containing carnosine, the carnosine may be derived from a component containing carnosine or may be contained in the agent as a component containing carnosine.

[0012] The component containing carnosine (carnosine-containing component) is not particularly limited, and examples thereof include plants containing carnosine [for example, Lamiaceae plants (herbs, etc.) such as rosemary and sage] and extracts thereof.

[0013] Note that for Lamiaceae plants and their extracts, for example, those described later may be used (or may be those described later).

[0014] The component containing carnosine may be used alone or in combination of two or more.

[0015] (β-Glucan) In an agent containing β-glucan, the β-glucan may be derived from a component containing β-glucan or may be contained in the agent as a component containing β-glucan.

[0016] The component containing β-glucan (β-glucan-containing component) is not particularly limited, and examples thereof include plants [for example, grains (for example, oats, barley, wheat, rye), seaweeds (for example, kelp)], fungi, bacteria, yeast (furthermore, extracts thereof), etc.

[0017] In particular, the component containing β-glucan may be a fungus.

[0018] Examples of the fungi include mushrooms such as Ganoderma lucidum (Reishi), shiitake mushroom, maitake mushroom, and Grifola frondosa. The fungi may be fermented [or may be a fermented product (self-digested product)]. Examples of such fungi include fermented Ganoderma lucidum (Ganoderma lucidum fermented product).

[0019] Note that for Ganoderma lucidum and Ganoderma lucidum extract, for example, those described later may be used (or may be those described later).

[0020] β-Glucan is not particularly limited in its structure or the like. For example, it may or may not have a β-1,6 bond (such as a β-1,6 bond of a glucose residue, a β-1,6 bond of a β-1,3-glucan side chain, etc.). Note that β-glucan having a β-1,6 bond may be contained in mushrooms and the like.

[0021] The molecular weight of β-glucan is not particularly limited. For example, it may be 1 kDa or more (such as 3 kDa or more, 5 kDa or more, 6 kDa or more), or may be 100 kDa or less (such as 50 kDa or less, 30 kDa or less, 22 kDa or less).

[0022] β-Glucan and components containing β-glucan may be used alone or in combination of two or more.

[0023] (Extract of Lamiaceae plants) In the extract of Lamiaceae plants, examples of the Lamiaceae plants include rosemary, sage, etc.

[0024] The Lamiaceae plants may particularly contain carnosine.

[0025] The Lamiaceae plants may be used alone or in combination of two or more.

[0026] In the extract, the part of the plant (Lamiaceae plant) is not particularly limited, and a general-purpose part may be used for each plant. As specific parts, for example, parts such as flowers, leaves, seeds (seeds, seed coats), stems, roots, etc. may be used, these may be used in combination, or the whole herb may be used.

[0027] Typically, at least flowers and leaves may be used. The part of the plant may be selected according to the type of the plant. For example, for rosemary, sage, etc., at least leaves may be used.

[0028] The extract may particularly contain carnosic acid.

[0029] The extract may be an extract of a plant (solvent extract).

[0030] The solvent (extraction solvent) is not particularly limited. For example, water, alcohols [e.g., alkanols (e.g., lower alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, etc. (C 1-4 alkanols, etc.)), polyols (or polyhydric alcohols, e.g., ethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin, etc.)], ketones (e.g., acetone, methyl ethyl ketone, etc.), ethers (e.g., diethyl ether, tetrahydrofuran, etc.), esters (e.g., ethyl acetate, etc.) and the like can be mentioned.

[0031] The extraction solvent may be used alone or in combination of two or more.

[0032] Typical extraction solvents include water, alcohols (e.g., lower alcohols such as ethanol), mixtures thereof, and the like.

[0033] In particular, as the solvent, a solvent containing at least a polar solvent (e.g., alcohols), particularly a solvent containing ethanol [e.g., a solvent containing 30% by volume (volume) or more of ethanol, preferably 50% by volume or more, more preferably 70% by volume or more (e.g., 90% by volume or more, etc.)] may be preferably used.

[0034] In the extraction, the ratio of the plant to the extraction solvent is not particularly limited. For example, the weight ratio of the plant / extraction solvent may be a ratio such that it is 1 / 1 to 1 / 100 (e.g., 1 / 2 to 1 / 50, 1 / 2 to 1 / 20, etc.).

[0035] The extraction temperature and extraction time are not particularly limited and can be appropriately selected according to the extraction solvent, extraction method, etc. For example, the extraction temperature may be about 15 to 150 °C, and the extraction time may be about 0.1 to 48 hours.

[0036] Note that in the extraction, the plant may be subjected to appropriate treatments (such as grinding treatment, heat treatment, drying treatment, etc.) as necessary. Further, the extract may be further subjected to concentration or drying (room temperature drying, freeze drying, etc.).

[0037] The form of the extract in the agent (and further the composition described later) is not particularly limited, and may be, for example, liquid (e.g., an extract containing an extraction solvent), powder (or powder granule), etc.

[0038] Commercially available products may be used for the extract, or those produced [e.g., those obtained by extracting a plant (a part of the plant) by the method as described above] may be used.

[0039] The extracts may be used alone or in combination of two or more.

[0040] When the extract contains carnosine, the proportion of carnosine in the extract (the proportion of carnosine in the total solid content of the extract) can be selected from a range of, for example, about 0.1% by mass or more (e.g., 0.3% by mass or more, 0.5% by mass or more), and can be 1% by mass or more (e.g., 1.5% by mass or more, 2% by mass or more, 2.5% by mass or more), preferably 3% by mass or more (e.g., 3.5% by mass or more, 4% by mass or more, 4.5% by mass or more), more preferably about 5% by mass or more (e.g., 5.5% by mass or more, 6% by mass or more, 6.2% by mass or more), and can also be about 8% by mass or more (e.g., 10% by mass or more, 15% by mass or more, 18% by mass or more, 18.6% by mass or more, 20% by mass or more, 30% by mass or more, 40% by mass or more, 50% by mass or more, 55% by mass or more, 55.7% by mass or more), and can also be about 95% by mass or less (e.g., 90% by mass or less, 85% by mass or less, 80% by mass or less, 75% by mass or less, 70% by mass or less, 65% by mass or less, 60% by mass or less, 58% by mass or less).

[0041] (Ganoderma lucidum extract) In the Ganoderma lucidum extract (extract of Ganoderma lucidum), Ganoderma lucidum is not particularly limited, and examples include Ganoderma lucidum, Ganoderma tsugae, Ganoderma luteum, Ganoderma atrum, Ganoderma leucocontextum, Ganoderma sinense, Ganoderma amboinense, etc. These can be used alone or in combination of two or more. Also, Ganoderma lucidum can be a natural product or a cultivated product, and those obtained by conventionally known acquisition methods can be used.

[0042] In the Ganoderma lucidum extract, the part of Ganoderma lucidum is not particularly limited, and any part can be used. Examples of the part of Ganoderma lucidum include the cap, the gill, the margin, the stalk, the pore, etc. These can be used alone or in combination of two or more.

[0043] In the Ganoderma lucidum extract, Ganoderma lucidum can particularly be fermented Ganoderma lucidum (Ganoderma lucidum fermented product, fermented product of Ganoderma lucidum) (it may be fermented).

[0044] The fermented Ganoderma lucidum is not particularly limited, but typically includes the autolysate of Ganoderma lucidum, etc.

[0045] Fermented Ganoderma lucidum (self-digested product) can be obtained, for example, by fermenting or aging Ganoderma lucidum at a predetermined temperature (for example, 30 to 40 °C, preferably about 35 to 40 °C). The fermentation time is not particularly limited and is, for example, 1 to 48 hours, preferably 1 to 30 hours. Note that the fermentation may be carried out in the presence of bacteria or the like that contribute to the fermentation of Ganoderma lucidum.

[0046] The fermentation may be carried out in the presence of water. The mode of allowing water to be present is not particularly limited, and examples include spraying and immersion.

[0047] Note that after fermentation, sterilization treatment (for example, heat sterilization, autoclaving, filtration sterilization, etc.) may be carried out as necessary.

[0048] The extract may particularly contain β-glucan (such as the aforementioned β-glucan).

[0049] Note that when the extract contains β-glucan, the ratio of β-glucan in the extract (the ratio of β-glucan in the total solid content of the extract) can be selected from, for example, a range of 0.01 mass% or more (for example, 0.05 mass% or more, 0.1 mass% or more), and can be 0.5 mass% or more (for example, 1 mass% or more), preferably 1.5 mass% or more (for example, 2 mass% or more), more preferably 2.5 mass% or more (for example, 3 mass% or more, 3.5 mass% or more, 4 mass% or more), and may also be 90 mass% or less (for example, 80 mass% or less, 70 mass% or less, 60 mass% or less, 50 mass% or less, 40 mass% or less, 30 mass% or less, 25 mass% or less, 20 mass% or less, 15 mass% or less, 10 mass% or less).

[0050] The extract may be an extract (solvent extract) of Ganoderma lucidum (fermented Ganoderma lucidum, etc.).

[0051] The solvent (extraction solvent) is not particularly limited, but examples include water and alcohols [for example, alkanols (for example, lower alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, etc., C 1-4Alkanols, etc.), polyols (or polyhydric alcohols, such as ethylene glycol, propylene glycol, 1,3 - butylene glycol, glycerin, etc.), ketones (such as acetone, methyl ethyl ketone, etc.), ethers (such as diethyl ether, tetrahydrofuran, etc.), esters (such as ethyl acetate, etc.), and the like can be mentioned.

[0052] The extraction solvent may be used alone or in combination of two or more.

[0053] Typical extraction solvents include water, alcohols (such as lower alcohols like ethanol), mixtures thereof, and the like.

[0054] In particular, among the extracts, the water extract of Ganoderma lucidum [especially the hot water extract (such as the product obtained by heating a mixture of Ganoderma lucidum and water at 90 - 130 °C, etc.)] may be preferably used.

[0055] The method for producing the solvent extract is not particularly limited. For example, it can be obtained by stirring a mixture of Ganoderma lucidum (such as fermented Ganoderma lucidum) and the extraction solvent as necessary.

[0056] Note that as the Ganoderma lucidum used for solvent extraction, Ganoderma lucidum may be used as it is, or Ganoderma lucidum may be used as a crushed product, powder, paste, etc.

[0057] In the extraction, the mixing ratio of Ganoderma lucidum and the extraction solvent is not particularly limited. For example, the weight ratio of Ganoderma lucidum / extraction solvent may be a ratio such that it is 1 / 1 - 1 / 100 (such as 1 / 2 - 1 / 50, 1 / 2 - 1 / 20), etc.

[0058] The extraction temperature and extraction time are not particularly limited and can be appropriately selected according to the extraction solvent, extraction method, etc. For example, the extraction temperature may be about 15 - 150 °C, and the extraction time may be about 0.1 - 48 hours.

[0059] The form of the extract in the agent (and further the composition described later) is not particularly limited, and may be, for example, liquid (e.g., an extract containing an extraction solvent), powdery (or granular), or the like.

[0060] Commercially available products may be used as the extract, or those produced [e.g., those obtained by subjecting Ganoderma lucidum (fermented Ganoderma lucidum, etc.) to an extraction treatment by the method as described above] may also be used.

[0061] The extracts may be used alone or in combination of two or more.

[0062] (Combination of components (component A)) As described above, the agent of the present invention contains at least one component selected from carnosic acid, β-glucan, an extract of a Lamiaceae plant, and a Ganoderma lucidum extract. In particular, these may be contained in combination of two or more. By combining them, the effects of the present invention can be achieved more efficiently.

[0063] Among such combinations, it is particularly preferable to contain a combination of at least one selected from carnosic acid and an extract of a Lamiaceae plant and at least one selected from β-glucan and a Ganoderma lucidum extract.

[0064] When combining at least one component selected from carnosic acid and extracts of Lamiaceae plants with at least one component selected from β-glucan and extracts of Ganoderma lucidum, the ratio of these components may be, for example, 0.0001 part by mass or more (such as 0.001 part by mass or more, 0.005 part by mass or more, 0.01 part by mass or more, 0.1 part by mass or more, 0.5 part by mass or more, 1 part by mass or more, 5 parts by mass or more, 10 parts by mass or more, 20 parts by mass or more, 30 parts by mass or more, 50 parts by mass or more, 70 parts by mass or more, 90 parts by mass or more) of the at least one component selected from β-glucan and extracts of Ganoderma lucidum per 1 part by mass of the at least one component selected from carnosic acid and extracts of Lamiaceae plants, and may also be 10,000 parts by mass or less (such as 5,000 parts by mass or less, 3,000 parts by mass or less, 2,000 parts by mass or less, 1,000 parts by mass or less, 800 parts by mass or less, 700 parts by mass or less, 600 parts by mass or less, 500 parts by mass or less, 400 parts by mass or less, 300 parts by mass or less, 200 parts by mass or less, 150 parts by mass or less).

[0065] When combining carnosic acid and β-glucan, the ratio of carnosic acid to β-glucan may be, for example, 0.0001 part by mass or more (such as 0.001 part by mass or more, 0.005 part by mass or more, 0.01 part by mass or more, 0.1 part by mass or more, 0.5 part by mass or more, 1 part by mass or more, 5 parts by mass or more, 10 parts by mass or more, 20 parts by mass or more, 30 parts by mass or more, 50 parts by mass or more, 70 parts by mass or more, 90 parts by mass or more) of β-glucan per 1 part by mass of carnosic acid, and may also be 10,000 parts by mass or less (such as 5,000 parts by mass or less, 3,000 parts by mass or less, 2,000 parts by mass or less, 1,000 parts by mass or less, 800 parts by mass or less, 700 parts by mass or less, 600 parts by mass or less, 500 parts by mass or less, 400 parts by mass or less, 300 parts by mass or less, 200 parts by mass or less, 150 parts by mass or less).

[0066] When combining carnosine and Ganoderma lucidum extract, the ratio of carnosine to Ganoderma lucidum extract may be, for example, 0.0001 parts by mass or more (e.g., 0.001 parts by mass or more, 0.005 parts by mass or more, 0.01 parts by mass or more, 0.1 parts by mass or more, 0.5 parts by mass or more, 1 part by mass or more, 5 parts by mass or more, 10 parts by mass or more, 20 parts by mass or more) of Ganoderma lucidum extract with respect to 1 part by mass of carnosine, and may also be 10,000 parts by mass or less (e.g., 5,000 parts by mass or less, 3,000 parts by mass or less, 2,000 parts by mass or less, 1,000 parts by mass or less, 800 parts by mass or less, 700 parts by mass or less, 600 parts by mass or less, 500 parts by mass or less, 400 parts by mass or less, 300 parts by mass or less, 200 parts by mass or less, 150 parts by mass or less, 100 parts by mass or less, 80 parts by mass or less, 50 parts by mass or less, 40 parts by mass or less).

[0067] When combining an extract of a Lamiaceae plant (e.g., rosemary extract) and β-glucan, the ratio of the extract of a Lamiaceae plant (e.g., rosemary extract) to β-glucan may be, for example, 0.0001 parts by mass or more (e.g., 0.001 parts by mass or more, 0.005 parts by mass or more, 0.01 parts by mass or more, 0.1 parts by mass or more, 0.5 parts by mass or more, 1 part by mass or more, 5 parts by mass or more, 10 parts by mass or more, 20 parts by mass or more, 30 parts by mass or more, 50 parts by mass or more, 70 parts by mass or more, 90 parts by mass or more) of β-glucan with respect to 1 part by mass of the extract of a Lamiaceae plant (e.g., rosemary extract), and may also be 10,000 parts by mass or less (e.g., 5,000 parts by mass or less, 3,000 parts by mass or less, 2,000 parts by mass or less, 1,000 parts by mass or less, 800 parts by mass or less, 700 parts by mass or less, 600 parts by mass or less, 500 parts by mass or less, 400 parts by mass or less, 300 parts by mass or less, 200 parts by mass or less, 150 parts by mass or less).

[0068] When combining an extract of a Lamiaceae plant (e.g., rosemary extract) with an extract of Ganoderma lucidum, the ratio of the extract of the Lamiaceae plant (e.g., rosemary extract) to the extract of Ganoderma lucidum may be, for example, 0.0001 part by mass or more (e.g., 0.001 part by mass or more, 0.005 part by mass or more, 0.01 part by mass or more, 0.1 part by mass or more, 0.5 part by mass or more, 1 part by mass or more, 5 parts by mass or more, 10 parts by mass or more, 20 parts by mass or more, 30 parts by mass or more) of the extract of Ganoderma lucidum with respect to 1 part by mass of the extract of the Lamiaceae plant (e.g., rosemary extract), and may also be 10,000 parts by mass or less (e.g., 5,000 parts by mass or less, 3,000 parts by mass or less, 2,000 parts by mass or less, 1,000 parts by mass or less, 800 parts by mass or less, 700 parts by mass or less, 600 parts by mass or less, 500 parts by mass or less, 400 parts by mass or less, 300 parts by mass or less, 200 parts by mass or less, 150 parts by mass or less).

[0069] (Use of the agent) The agent of the present invention can be used for specific applications.

[0070] First, the agent of the present invention can be used as an agent for promoting the expression of CD39 [an agent for promoting (improving, enhancing, activating) the expression (production) of CD39].

[0071] Furthermore, the agent of the present invention may be used for applications related to (or reported to be related to) promoting the expression of CD39, for example, at least one application selected from the following (1) to (3). (1) Suppression or improvement of inflammation (e.g., suppression of skin inflammation) (2) Maintenance of homeostasis (e.g., maintenance of skin homeostasis) (3) Suppression of external stimulus response (calming) (e.g., suppression of external stimulus response in the skin)

[0072] Note that these may be caused by extracellular ATP (e.g., in these applications, inflammation, external stimulus response, immune response, etc. are caused by extracellular ATP).

[0073] Furthermore, the agent of the present invention may be used as an agent for a specific application target, for example, for pharmaceutical use, food and drink use, cosmetic use, etc.

[0074] [Composition, etc.] The present invention also includes a composition containing at least one component (Component A) selected from the above agent [or carnosine, β-glucan, extract of Lamiaceae plants, and Ganoderma lucidum extract].

[0075] In this composition, the form (specific form, preferred form, etc.) of the above agent (or Component A) is the same as described above.

[0076] And such a composition can also be used for the same functions and applications as the above agent. For example, it can be used for promoting the expression of CD39 and applications related to promoting the expression of CD39 (for example, at least one application selected from (1) to (3), etc.).

[0077] (1) Suppression or improvement of inflammation (for example, suppression of skin inflammation) (2) Maintenance of homeostasis (for example, maintenance of skin homeostasis) (3) Suppression of external stimulus response (calming) (for example, suppression of external stimulus response in the skin)

[0078] Note that such functions and applications may also be those having Component A as the active ingredient, similar to the above agent.

[0079] Also, the composition (agent, Component A, hereinafter sometimes collectively referred to as the composition) may be used as a pharmaceutical, quasi-drug, food or drink, cosmetic, etc.

[0080] Foods and drinks (beverages and foods) include, in addition to general foods and drinks, health foods [including health functional foods (specific health foods, nutritional functional foods, foods with function claims)], supplements (nutritional supplements), feeds, etc.

[0081] In particular, the composition of the present invention may be preferably used as a cosmetic (cosmetic composition). Note that the cosmetic composition is not particularly limited and may be classified as a quasi-drug in the definition in the Pharmaceutical Affairs Law, such as medicinal cosmetics.

[0082] The composition of the present invention only needs to contain the agent or component A, and may contain other components according to its use, form, and the like.

[0083] Examples of such other components (components other than component A) include bases or carriers, additives, and other active ingredients. Note that such other components and their ratios can be appropriately selected according to the form, properties, and the like of the composition.

[0084] The base or carrier is not particularly limited. For example, hydrocarbons such as paraffin, liquid paraffin, squalane, white wax, gelled hydrocarbon (such as Plastibase), ozokerite, ceresin, petrolatum, hard fat, microcrystalline wax, α-olefin oligomer, and light liquid paraffin; fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and isostearic acid; triglyceride fatty acid glycerides such as glyceryl tri-2-ethylhexanoate (trioctanoin) and glyceryl tri(caprylic acid / capric acid); higher alcohols such as cetyl alcohol, stearyl alcohol, and behenyl alcohol; silicone oils such as methyl polysiloxane, highly polymerized methyl polysiloxane, dimethylsiloxane·methyl(polyoxyethylene)siloxane·methyl(polyoxypropylene)siloxane copolymer, dimethylsiloxane·methyl(polyoxyethylene)siloxane copolymer, dimethylsiloxane·methyl(polyoxypropylene)siloxane copolymer, polyoxyethylene·methyl polysiloxane copolymer, poly(oxyethylene·oxypropylene)·methyl polysiloxane copolymer, dimethylsiloxane·methyl cetyloxysiloxane copolymer, dimethylsiloxane·methyl stearoxysiloxane copolymer, acrylic acid alkyl copolymer methyl polysiloxane ester, crosslinked methyl polysiloxane, crosslinked methyl phenyl polysiloxane, crosslinked polyether-modified silicone, crosslinked alkyl polyether-modified silicone, crosslinked alkyl-modified silicone, decamethylcyclopentasiloxane, ethyl trisiloxane, methyl trimethicone, methyl siloxane network polymer, polyoxyethylene·methyl polysiloxane copolymer, methyl hydrogen polysiloxane, triethoxysilylethyl polydimethylsiloxyethyl hexyl dimethicone, and dimethyl polysiloxane; glycol acetates such as ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, hexylene glycol diacetate, and 2-methyl-2-propene-1,1-diol diacetate;Glycol esters such as triethylene glycol dibenzoate, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, 2,2,4-trimethyl-1,3-pentanediol diisobutyrate; Glycol acrylates such as ethylene glycol diacrylate, diethylene glycol diacrylate, propylene glycol monoacrylate, 2,2-dimethyl-trimethylene glycol diacrylate, and 1,3-butylene glycol diacrylate; Glycol dinitrates such as ethylene glycol dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate, and propylene glycol dinitrate; 2,2’-[1,4-phenylenedioxy]diethanol; Cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose; Polyvinyl pyrrolidone; Carrageenan; Polyvinyl butyrate; Polyethylene glycol; Dioxane; Butylene glycol adipic acid polyester; Esters such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerythritol tetra(2-ethylhexanoate); Polysaccharides such as dextrin, maltodextrin; Lower alcohols such as ethanol, isopropanol; Glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether; Aqueous bases such as water, etc. These bases or carriers can be used alone or in combination of two or more kinds.;

[0085] The additives are not particularly limited. For example, antioxidants, surfactants, thickeners, preservatives, pH adjusters, stabilizers, antiseptics, colorants, fragrances, excipients, binders, disintegrants, lubricants, etc. can be mentioned. These additives can be used alone or in combination of two or more.

[0086] Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivatives (such as ascorbic acid phosphate ester), tocopherol, tocopherol derivatives, erythorbic acid, L-cysteine hydrochloride, etc.

[0087] Examples of the surfactant include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexanoate, diglycerol sorbitan tetra-2-ethylhexanoate; propylene glycol fatty acid esters such as propylene glycol monostearate; glycerin alkyl ether; alkyl glucoside; amines such as stearylamine and oleylamine; silicone surfactants such as polyoxyethylene·methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, PEG-9 polydimethylsiloxyethyl dimethicone, etc.

[0088] Examples of the thickener include guar gum, locust bean gum, carrageenan, xanthan gum, polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, acrylic acid methacrylic acid alkyl copolymer, polyethylene glycol, bentonite, alginic acid, macrogol, and cellulose-based thickeners (such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and carboxyethyl cellulose, etc.) and their salts, etc.

[0089] Examples of preservatives and antiseptics include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, benzyl paraoxybenzoate, methyl paraoxybenzoate, phenoxyethanol, benzyl alcohol, chlorobutanol, sorbic acid and its salts, chlorhexidine gluconate, alkanediol, and glycerin fatty acid ester, etc.

[0090] Examples of pH adjusters include inorganic acids (such as hydrochloric acid, sulfuric acid, etc.), organic acids (such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (such as potassium hydroxide, sodium hydroxide, etc.), organic bases (such as triethanolamine, diisopropanolamine, triisopropanolamine, etc.), etc.

[0091] Examples of stabilizers include sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole, edetate salts, etc.

[0092] Examples of excipients include lactose, corn starch, sucrose, glucose, mannitol, sorbitol, crystalline cellulose, silicon dioxide, etc.

[0093] Examples of binders include polyvinyl alcohol, gelatin, methylcellulose, ethylcellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl acetal diethylaminoacetate, corn starch, etc.

[0094] Examples of disintegrants include corn starch, low-substituted hydroxypropyl cellulose, crospovidone, crystalline cellulose, precipitated calcium carbonate, croscarmellose sodium, calcium citrate, dextrin, pectin, carboxymethyl cellulose calcium, and the like.

[0095] Examples of lubricants include magnesium stearate, talc, polyethylene glycol, light anhydrous silicic acid, sucrose fatty acid ester, and the like. Examples of flavoring and odor-masking agents include cocoa powder, menthol, aromatic powder, peppermint oil, borneol, cinnamon powder, and the like.

[0096] Other active ingredients are not particularly limited, and examples include moisturizing ingredients, anti-inflammatory ingredients, antibacterial or bactericidal ingredients, vitamins, peptides or their derivatives (esters, amides, etc.), cell-activating ingredients, anti-aging ingredients, blood circulation-promoting ingredients, keratolytic ingredients, whitening ingredients, astringent ingredients, and the like. These active ingredients can be used alone or in combination of two or more.

[0097] Examples of moisturizing ingredients include high molecular weight compounds such as collagen, elastin, keratin, chitin, and chitosan; natural moisturizing factors such as sodium lactate, urea, and sodium pyrrolidone carboxylate; lipids such as ceramide, cholesterol, and phospholipid; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and perilla extract.

[0098] Examples of anti-inflammatory ingredients include ingredients derived from plants (e.g., comfrey), allantoin, glycyrrhizic acid or its derivatives, zinc oxide, pyridoxine hydrochloride, tocopherol acetate, salicylic acid or its derivatives, ε-aminocaproic acid, and the like.

[0099] Examples of antibacterial or bactericidal components include ethanol, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, sulfur, resorcinol, benzethonium chloride, adapalene, benzoyl peroxide, clindamycin, cresol, gluconic acid and its derivatives, povidone iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer No. 101, photosensitizer No. 201, parabens, phenoxyethanol, 1,2-pentanediol, alkyl diaminoglycine hydrochloride, chlorhexidine gluconate, zinc paraphenolsulfonate, etc.

[0100] Examples of vitamins include vitamin A derivatives such as retinol, retinol acetate, retinol palmitate, etc., retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoate, d-δ-tocopheryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate, etc.; vitamin E derivatives such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, calcium dl-α-tocopherol succinate, etc.; vitamin B2 derivatives such as riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, sodium riboflavin 5'-phosphate, riboflavin tetranicotinate, etc.; nicotinic acid derivatives such as nicotinic acid dl-α-tocopherol, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, 1-(4-methylphenyl)ethyl nicotinate, etc.; vitamin C derivatives such as ascorbigen-A, stearic acid ascorbate, palmitic acid ascorbate, L-ascorbyl dipalmitate, etc.; vitamin D derivatives such as methyl hesperidin, ergocalciferol, cholecalciferol, etc.; vitamin K derivatives such as phylloquinone, menaquinone, etc., γ-oryzanol, dibenzoyl thiamine, dibenzoyl thiamine hydrochloride; vitamin B1 derivatives such as thiamine hydrochloride, cetyl thiamine hydrochloride, thiamine thiocyanate, lauryl thiamine hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate ester phosphate, thiamine monophosphate ester, thiamine diphosphate ester, thiamine diphosphate ester hydrochloride, thiamine triphosphate ester, thiamine triphosphate ester monophosphate, etc.; vitamin B6 derivatives such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, pyridoxal 5'-phosphate, pyridoxamine hydrochloride, etc.; vitamin B12 derivatives such as cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin, etc.; folic acid derivatives such as folic acid, pteroylglutamic acid, etc.; nicotinic acid derivatives such as nicotinic acid, nicotinamide, etc.;Pantothenic acids such as pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantethine, D-pantethine, coenzyme A, pantothenyl ethyl ether, etc.; biotin such as biotin, biotitin, etc.; vitamin C such as ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate ester, magnesium ascorbate phosphate ester, etc.; vitamin-like factors such as carnitine, ferulic acid, α-lipoic acid, orotic acid, etc.

[0101] Examples of peptides or their derivatives include keratin-degrading peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin-degrading peptides, collagen-degrading peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin-degrading peptides, conchiolin-degrading peptides, hydrolyzed conchiolin, silk protein-degrading peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soy protein-degrading peptides, hydrolyzed soy protein, wheat protein, wheat protein-degrading peptides, hydrolyzed wheat protein, casein-degrading peptides, acylated peptides (such as palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.).

[0102] Examples of cell-activating components include vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, pantothenic acids, etc.; α-hydroxy acids such as glycolic acid, lactic acid, etc.; tannins, flavonoids, saponins, allantoin, photosensitizer No. 301, etc.

[0103] Examples of anti-aging components include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, etc.

[0104] Examples of the blood circulation promoting components include components derived from plants (e.g., carrot, ashitaba, arnica, ginkgo, eucommia, gentiana, burdock, rice, Japanese quince, European quince, European spindle tree, Chinese foxglove, dwarf lilyturf, thyme, clove, Chinese quince, angelica, cinnamon, torreya, carrot, garlic, butcher's broom, grape, button, plane tree, lemon balm, yuzu, licorice, rose hip, peach, apricot, walnut, corn); glucosyl hesperidin, etc.

[0105] Examples of the horny layer softening components include salicylic acid, glycolic acid, fruit acid, phytic acid, sulfur, etc.

[0106] Examples of the whitening components include ascorbic acid and its derivatives (such as phosphate esters), arbutin, tocopherol, etc.

[0107] Examples of the astringent components include zinc paraphenolsulfonate, zinc oxide, menthol, ethanol, etc.

[0108] The shape of the composition of the present invention is not particularly limited and can be appropriately selected according to the use, etc., and examples thereof include liquid, fluid, semi-solid, etc.

[0109] In addition, the form of the composition of the present invention (such as a composition for cosmetics) is not particularly limited, and examples thereof include a liquid agent, a suspension agent, an emulsion, a cream agent, an ointment agent, a gel agent, a liniment agent, a lotion agent, an aerosol agent, a sheet agent in which a non-woven fabric is impregnated with a chemical solution, etc. Among these, preferably, a liquid agent, a suspension agent, an emulsion, a cream agent, etc. are included.

[0110] The specific uses of the composition of the present invention are not particularly limited. For example, basic cosmetics such as lotion, emulsion, cosmetic oil, gel, cream, essence, sunscreen cosmetics, pack, mask, hand cream, body lotion, body cream, etc.; cleansing cosmetics such as facial cleanser, makeup remover, body shampoo, shampoo, conditioner, treatment, etc.; makeup cosmetics such as makeup base, foundation, face powder, white powder, powder, doran, eyeshadow base, eyeshadow, nose shadow, lip pencil, lipstick, lip gloss, blusher, various colors, etc.; hair care products such as shampoo, dry shampoo, conditioner, conditioner, rinse-in shampoo, treatment, hair tonic, hair styling agent, hair oil, pomade, hair colorant, etc.; dentifrice, lip cream, soap, body soap, etc. can be mentioned.

[0111] Among these, preferably, they are lotion, emulsion, cosmetic oil, gel, cream, essence, sunscreen cosmetics, etc., and more preferably, they are lotion, emulsion, cream, essence, etc.

[0112] When the composition of the present invention is quasi-drug or the like, the specific uses are not particularly limited. For example, pharmaceutical cosmetics, medicinal soap, medicinal dentifrice, antiperspirant, medicinal cream, hair growth agent, hair dye, gargle, drink agent, oral coolant, contact lens wearing medicine, bactericidal disinfectant, medicine for chilblains, digestive medicine, health medicine containing crude drugs, health medicine containing vitamins, bath agent, etc. can be mentioned. Among these, preferably, they are pharmaceutical cosmetics, medicinal cream, hair growth agent, etc.

[0113] Further, when the composition of the present invention is ingested (administered), the form of the composition (form of the preparation) includes, for example, tablets, powders, fine granules, granules, capsules (soft capsules, hard capsules, etc.), liquids (suspensions, syrups, etc.), troches, jelly agents, suppositories, injections, sprays, etc.

[0114] In particular, when used as a health food or the like, for example, tablets, powders, fine granules, granules, capsules, emulsions, jelly agents, etc. are suitable.

[0115] Also, when the composition (agent, component A) is added (mixed, blended) to food and drink products (general food and drink products) for use, the food and drink products are not particularly limited. For example, food products [such as noodles (buckwheat noodles, udon noodles, Chinese noodles, instant noodles, etc.), confectioneries (molasses, candy, gum, chocolate, snack foods (potato chips, etc.), biscuits, cookies, gummies, jelly, jam, butter, cream (such as cream puffs, etc.), cakes, etc.), breads, processed fishery or livestock products (kamaboko, ham, sausage, etc.), dairy products (processed milk, fermented milk, etc.), oils and fat-processed foods (salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing, etc.), seasonings (sauces, tare, etc.), retort foods (curry, stew, donburi, rice porridge, mixed rice, etc.), frozen desserts (ice cream, sherbet, shaved ice, etc.), fried foods (croquettes, French fries, fried chicken, etc.), etc.], beverage products (tea beverages, soft drinks, carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages, etc.), etc. can be mentioned.

[0116] The ratio of the agent (component A) or the composition in the food and drink product can be selected according to the type of the food and drink product, the intake amount, etc. For example, as component A, it may be 0.0001% by mass or more (for example, 0.001 - 30% by mass), 0.003% by mass or more (for example, 0.005 - 20% by mass), 0.01% by mass or more (for example, 0.05 - 10% by mass), etc.

[0117] The manufacturing method of the composition of the present invention is not particularly limited as long as it is a method of using the agent or component A of the present invention, and a conventionally known method can be used according to the use, properties, etc. of the composition. For example, the agent or component A of the present invention can be manufactured by blending it as it is, or by emulsifying, solubilizing, or dispersing it during the manufacture of the composition by a conventional method.

[0118] In the composition of the present invention, the proportion of the agent of the present invention or component A can be appropriately selected depending on the type of the composition, the compounding components, etc., and is not particularly limited. For example, as the proportion of component A (proportion in terms of solid content), for example, it may be 0.00001% by mass or more, preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, etc.

[0119] The upper limit of the proportion of component A (proportion in terms of solid content) is not particularly limited. For example, it may be 0.0001% by mass, 0.0003% by mass, 0.001% by mass, 0.003% by mass, 0.01% by mass, 0.03% by mass, 0.05% by mass, 0.1% by mass, 0.3% by mass, 0.5% by mass, 1% by mass, etc.

[0120] [Usage modes, etc.] The present invention includes various methods using the above agent or composition.

[0121] Such a method may be, for example, a method of using the above agent or composition on a use (application) target.

[0122] Use (application, ingestion, administration) targets include humans and non-human animals (e.g., dogs, cats, etc.). The target may be a specific target (e.g., for women, for the elderly, for patients or the sick, etc.).

[0123] The use (application) form of the above agent (component A) or composition can be selected according to the form of the agent or composition, etc., and is not particularly limited. It may be application, etc., may be oral (for oral use), or may be parenteral (for parenteral use). Examples of parenteral administration (parenteral ingestion) include rectal administration, injection administration (e.g., intravenous administration, intrathecal administration, intramuscular administration, subcutaneous administration, intraperitoneal administration, intraarterial administration, intra-articular administration, intradermal administration, intralesional administration), etc.

[0124] The method of using (applying) the agent or composition of the present invention is not particularly limited and can be appropriately selected according to the object of use (application) and the like. For example, when used for cosmetics or the like, it can be appropriately selected according to the skin condition, age, gender, etc. For example, it can be applied (coated, sprayed, pasted, etc.) to the skin several times a day (for example, 1 to 5 times a day, preferably 1 to 3 times a day) in an appropriate amount (for example, about 0.005 to 0.5 g). Also, it can be applied to any skin such as the face, neck, hands, feet, fingers, torso, scalp, etc.

[0125] The amount of use (application) of the agent or composition of the present invention is also not particularly limited and can be appropriately changed according to the type and components of the composition. For example, as the ratio of component A (ratio in terms of solid content), per adult per day, 0.0001 to 100 mg / cm 2 (skin area), preferably 0.001 to 10 mg / cm 2 (skin area) etc. may be sufficient.

[0126] The amount of use (intake, dosage, dose) of the agent or composition of the present invention can be selected according to the degree of the disease and symptoms. For example, as component A per day, 0.01 mg or more (for example, 0.01 to 1000 mg), preferably 0.1 mg or more (for example, 0.1 to 100 mg), more preferably about 1 mg or more (for example, 1 to 10 mg) may be sufficient.

[0127] And such a method (use) may be accompanied by the above-mentioned functions and actions (for example, promotion of CD39 expression, suppression or improvement of inflammation, maintenance of homeostasis, etc.).

[0128] That is, the agent or composition of the present invention is applicable to various uses as described above. Therefore, the present invention also includes a method corresponding to such uses.

[0129] First, in the method of the present invention, by using (intaking, administering, causing to take) the agent or composition to a subject, the expression of CD39 is promoted.

[0130] In addition, as described above, by promoting the expression of CD39, related functions can be expressed [symptoms / diseases can be improved (treated, suppressed)].

[0131] Therefore, the present invention includes a method of expressing [improving (treating, suppressing) symptoms / diseases] related to promoting the expression of CD39 by using (administering, ingesting, causing to take) the agent or composition to a subject.

[0132] Examples of such methods include, for example, methods corresponding to the uses (1) to (4) above, that is, the following (1A), (2A), (3A), (4A), etc.

[0133] (1A) A method of suppressing or improving inflammation (for example, suppressing or improving skin inflammation) by using (administering, ingesting, causing to take) the agent or composition to a subject (2A) A method of maintaining (retaining) homeostasis (for example, maintaining skin homeostasis) by using (administering, ingesting, causing to take) the agent or composition to a subject (3A) A method of suppressing (calming) the external stimulus response (for example, suppressing the external stimulus response in the skin) by using (administering, ingesting, causing to take) the agent or composition to a subject (4A) A method of suppressing (calming) the immune response (for example, suppressing the immune response in the skin) by using (administering, ingesting, causing to take) the agent or composition to a subject

[0134] In the above methods, the specific form, intake amount, etc. of the agent or composition may be the same as those described above.

Examples

[0135] Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto.

[0136] [Synthesis Example] (Production of Rosemary Extract) After pulverizing 20 g of rosemary leaves into powder using a mixer, 4 times the amount of a 50% or 90% by volume ethanol aqueous solution was added, and extraction was carried out at 40 °C for 3 hours. After filtering the obtained extract, it was distilled off using an evaporator. After distillation, water was added and then freeze-dried to obtain a powdery rosemary extract (extract).

[0137] In addition, as a result of analysis by HPLC (high performance liquid chromatography), it was confirmed that the rosemary extract contains carnosic acid and rosmarinic acid in both the 50% by mass ethanol aqueous solution and the 90% by mass ethanol aqueous solution.

[0138] The HPLC analysis was carried out as follows (hereinafter, the same applies to the HPLC analysis). In HPLC (manufactured by Shimadzu Corporation), a reverse phase system using μ-BONDSPHERE (I.D. 150×3.9 mm, C18 5 μm; manufactured by Waters Corporation) as the separation column was used, and analysis was carried out under gradient conditions using acetonitrile and 2% acetic acid as the mobile phase. Starting from a 15% acetonitrile solution with the column oven set at 40 °C, the concentration was increased to 20% between 0 minutes and 10 minutes, to 40% between 10 minutes and 10.1 minutes, and to 70% between 10.1 minutes and 40 minutes, and then a washing step with 100% acetonitrile was used. Detection was carried out at 280 nm at a flow rate of 1 mL / min. The sample injection volume was 10 μL.

[0139] (Production of fermented Ganoderma lucidum extract) 12 L of water was added to 800 g of Ganoderma lucidum powder obtained by pulverizing Ganoderma lucidum (fruiting body), and after stirring at 37 °C for 24 hours, it was heat-sterilized at 121 °C for 15 minutes, filtered through a filter, and the obtained extract was freeze-dried to obtain a powder, and a Ganoderma lucidum fermented product was obtained. 100 ml of water was added to 10 g of this Ganoderma lucidum fermented product powder, extraction was carried out at 90 °C for 2 hours, filtered, and then freeze-dried to obtain a powdery Ganoderma lucidum fermented product extract (fermented Ganoderma lucidum extract).

[0140] (Production of β-glucan) 800 g of Ganoderma lingzhi (sporophore) powder was added with 12 L of water, stirred at 37°C for 24 hours, heat-sterilized at 121°C for 15 minutes, filtered through a filter, and the resulting extract was freeze-dried into a powder to obtain a Ganoderma lingzhi fermented product. 10 times the amount of water was added to the obtained Ganoderma lingzhi fermented product, and extraction was carried out at 85°C for 2 hours. Ethanol was added to the extract to a concentration of 70%, and it was left standing at room temperature for 16 hours. The precipitate was collected, frozen into a powder, and this was used as the Ganoderma lingzhi fermented product polysaccharide fraction. Furthermore, this Ganoderma lingzhi fermented product polysaccharide fraction was separated by column chromatography using Toyopearl HW-55F (manufactured by Tosoh Corporation) with 0.1 M phosphate buffer as the eluent to obtain a peak of about 6 kDa to about 22 kDa, and desalted by a dialysis membrane to obtain β-glucan derived from the Ganoderma lingzhi fermented product [fermented Ganoderma lingzhi (extract)].

[0141] (Test) THP-1 cells were used as alternative cells for human Langerhans cells. Approximately 200,000 THP-1 cells were seeded and cultured in RPMI1640 medium supplemented with 10% FBS for 72 hours. After 72 hours, dexamethasone was added to the medium as a stress hormone to a final concentration of 100 nM, and then the test sample was added and cultured for 24 hours. After culturing, the medium was removed, total RNA was extracted with TRIzol (manufactured by Thermo Fisher), the amount of each RNA was measured with a spectrophotometer, and the total RNA was prepared to be 100 ng / μL. Using this RNA as a template, cDNA was synthesized by reverse transcriptase, and then the expression levels of mRNA for template CD39 and the internal standard GAPDH were measured. Detection was performed by RT-PCR reaction using a real-time PCR device (manufactured by Bio-Rad) with Takara SYBR PrimeScript RT-PCR kit (Perfect Real Tim) (Takara Bio Inc.). The expression level of CD39 mRNA was corrected with the value of GAPDH based on the total RNA samples prepared from the cells cultured in the "stress hormone + test sample addition group" and the "stress hormone addition group", respectively. From the obtained values, the CD39 expression promotion rate was calculated according to the following formula.

[0142] CD39 (CD39 mRNA) expression promotion rate (%) = (Expression level of CD39 mRNA in the stress hormone + test sample addition group / Expression level in the stress hormone only addition group) × 100

[0143] (Example 1) Promotion of CD39 expression by carnosinic acid The above test was performed by adding carnosine acid as the test sample to the medium at a predetermined concentration, and the CD39 expression promotion rate was calculated. Note that carnosine acid was added as an aqueous solution (the same applies hereinafter).

[0144] The results are shown in the following table.

[0145]

Table 1

[0146] (Reference Example 1) Promotion of CD39 expression by rosmarinic acid When the above test was performed by adding rosmarinic acid (a component known to be contained in rosemary, etc.) as the test sample to the medium at a concentration of 50 μM and calculating the CD39 expression promotion rate, it was 97 (%). From this, it was found that rosmarinic acid may not (almost) promote the expression of CD39 but rather attenuate it. Note that rosmarinic acid was added as an aqueous solution (the same applies hereinafter).

[0147] (Example 2) Promotion of CD39 expression by β-glucan The above test was performed by adding the β - glucan obtained in the synthesis example as the test sample to the medium at a predetermined concentration, and the CD39 expression promotion rate was calculated. Note that β - glucan was added as an aqueous solution.

[0148] The results are shown in the following table.

[0149]

Table 2

[0150] (Example 3) Promotion of CD39 expression by rosemary extract The rosemary extract obtained in the synthesis example as the test sample was added to the medium at a predetermined concentration, and the above test was performed to calculate the CD39 expression promotion rate. The rosemary extract was added as an aqueous solution (the same applies hereinafter).

[0151] The results are shown in the following table.

[0152]

Table 3

[0153] As described above, the rosemary extract obtained in the synthesis example contains carnosine acid. However, from the results of HPLC analysis, when the concentration of the rosemary extract to be added is converted to the concentration of carnosine acid (carnosine acid derived from the rosemary extract), for example, it is 6.13 μM at 11.1 μg / mL of the 90% by mass ethanol aqueous solution extract and 18.4 μM at 33.3 μg / mL of the 90% by mass ethanol aqueous solution extract.

[0154] (Example 4) Promotion of CD39 expression by fermented ganoderma extract The fermented ganoderma extract obtained in the synthesis example as the test sample was added to the medium at a predetermined concentration, and the above test was performed to calculate the CD39 expression promotion rate. The fermented ganoderma extract was added as an aqueous solution (the same applies hereinafter).

[0155] The results are shown in the following table.

[0156]

Table 4

[0157] (Example 5) Promotion of CD39 expression by the combined system of carnosinic acid and fermented ganoderma extract The carnosine acid as a test sample and the fermented Ganoderma lucidum extract obtained in the synthesis example were added to the medium at a predetermined concentration, and the above test was conducted to calculate the CD39 expression promotion rate.

[0158] The results are shown in the following table.

[0159]

Table 5

[0160] (Example 6) Promotion of CD39 expression by the combined system of rosemary extract and fermented ganoderma extract The rosemary extract (90% by volume ethanol aqueous solution extract) obtained in the synthesis example and the fermented Ganoderma lucidum extract obtained in the synthesis example as test samples were added to the medium at a predetermined concentration, and the above test was conducted to calculate the CD39 expression promotion rate.

[0161] The results are shown in the following table.

[0162]

Table 6

[0163] Hereinafter, specific examples of the composition of the present invention will be exemplified.

[0164] Formulation Example 1: Lotion A lotion having the following composition is manufactured according to the following preparation method. The following components are formulated so that the total is 100% by weight. All components are mixed and stirred at room temperature to form a uniform solution, and the pH is adjusted to 5.5 to obtain a lotion. Component Weight % Concentrated glycerin 4.0 Sorbitol 4.0 Sodium citrate 0.3 Polyoxyethylene hydrogenated castor oil 0.5 Fermented Ganoderma lucidum extract 0.1 Rosemary extract 0.1 Ethanol 15.0 Fragrance 0.005 Citric acid Appropriate amount Purified water Remainder

[0165] Formulation Example 2: Facial Cleanser Manufacture a facial cleanser with the following composition according to the following preparation method. Formulate each of Components A, B, and C in the following ratios so that the total of Components A, B, and C is 100% by weight. First, heat and dissolve the mixture of Component A and maintain it at 80°C. Next, add the separately heated and dissolved mixture of Component B at 80°C to the mixture of Component A and stir well. Then, cool with stirring and add the mixture of Component C at 50°C to obtain a facial cleanser. "Component A" Component % by weight Myristic acid 14.0 Stearic acid 12.0 Lauric acid 3.5 Oleyl alcohol 1.5 Coconut oil fatty acid amide propyl betaine 10.5 "Component B" Component % by weight Concentrated glycerin 18.0 Potassium hydroxide 7.0 Paraoxybenzoic acid ester Appropriate amount Purified water Remainder "Component C" Component % by weight Fermented Ganoderma lucidum extract 0.1 Rosemary extract 0.1 Fragrance Appropriate amount

[0166] Formulation Example 3: Emulsion Manufacture an emulsion with the following composition according to the following preparation method. Formulate each of Components D, E, and F in the following ratios so that the total of Components D, E, and F is 100% by weight. First, heat and dissolve the mixture of Component D and maintain it at 80°C. Next, add the separately heated and dissolved mixture of Component E at 80°C to the mixture of Component D and stir well. Then, cool with stirring and add the mixture of Component F at 50°C to obtain an emulsion. "Component D" Component % by weight Sucrose fatty acid ester 1.0 Carboxyvinyl polymer 0.06 Potassium hydroxide 0.028 Paraoxybenzoic acid ester Appropriate amount Purified water The balance "Component E" Component Weight % Olive oil 4.0 Jojoba oil 4.0 Myristyl lactate 2.0 Self-emulsifying glycerol monostearate 1.5 Lipophilic glycerol monostearate 1.5 "Component F" Component Weight % Fermented Ganoderma lucidum extract 0.1 Rosemary extract 0.1 Fragrance 0.2

Industrial applicability

[0167] According to the present invention, an agent effective for promoting the expression of CD39 or the like can be provided.

Claims

1. An agent or composition for promoting CD39 expression, comprising carnosine acid.

2. An agent or composition for promoting CD39 expression, comprising an extract of a Lamiaceae plant.

3. An agent or composition for promoting CD39 expression, comprising β-glucan derived from fermented Ganoderma lucidum.

4. An agent or composition for promoting CD39 expression, comprising an extract of fermented Ganoderma lucidum.

5. An agent or composition for promoting CD39 expression, comprising carnosine acid and an extract of fermented Ganoderma lucidum.

6. An agent or composition for promoting CD39 expression, comprising an extract of a Lamiaceae plant and an extract of fermented Ganoderma lucidum.

7. An agent or composition comprising at least one selected from carnosine acid, an extract of a Lamiaceae plant, β-glucan derived from fermented Ganoderma lucidum, and an extract of fermented Ganoderma lucidum, and used for at least one use selected from the following (1) to (3). (1)Suppression or improvement of inflammation (2)Maintenance of homeostasis (3)Suppression of external stimulus response

8. The agent or composition according to claim 2, 6 or 7, wherein the extract of the Lamiaceae plant comprises rosemary extract.

9. The agent or composition according to claim 2, 6 or 7, wherein the extract of the Lamiaceae plant comprises an extract in at least one solvent selected from water, alcohols, and mixed solvents thereof.

10. The agent or composition according to claim 4 or 7, wherein the extract of fermented Ganoderma lucidum comprises an extract in at least one solvent selected from water, alcohols, and mixed solvents thereof.

11. Comprising at least carnosine acid and an extract of fermented Ganoderma lucidum, The agent or composition according to claim 5 or 7, wherein the ratio of carnosine acid to the extract of fermented Ganoderma lucidum is 0.01 to 1000 parts by mass of the extract of fermented Ganoderma lucidum per 1 part by mass of carnosine acid.

12. Comprising at least an extract of a Lamiaceae plant and an extract of fermented Ganoderma lucidum, The agent or composition according to claim 6 or 7, wherein the ratio of the extract of the Lamiaceae plant to the extract of fermented Ganoderma lucidum is 0.1 to 3000 parts by mass of the extract of fermented Ganoderma lucidum per 1 part by mass of the extract of the Lamiaceae plant.

13. The composition according to any one of claims 1 to 7, which is a cosmetic.

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