JP2024078351A - DKK1 expression promoter - Google Patents

Abstract

The present invention provides an agent useful for promoting DKK1 expression, etc.
The agent contains an extract of at least one plant selected from the group consisting of plants of the genus Mint, the genus Carthamus, the genus Eyelash, the genus Hibiscus, and the genus Honeysuckle.
[Selection diagram] None

Description

The present invention relates to an agent that is useful for promoting the expression (production) of DKK1.

DKK1 is highly expressed in the skin of the palms and soles, where skin color does not change easily, and is secreted from dermal fibroblasts. It inhibits Wnt signal activation in melanocytes, suppressing their differentiation and proliferation (Non-Patent Documents 1 and 2). It has also been reported that it inhibits melanin transfer in keratinocytes (Non-Patent Document 3).
From the above, it is believed that pigmentation in the epidermis can be suppressed by promoting the expression of DKK1, which inhibits Wnt signal activation.

Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation.(J. Cell Biol. 2004, 165, 275-285.) The Effects of Dickkopf 1 on Gene Expression and Wnt Signaling by Melanocytes: Mechanisms Underlying Its Suppression of Melanocyte Function and Proliferation(J. Invest. Dermatol. 2007, 127, 1217-1225.) Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting Wnt/β catenin signaling in keratinocytes.(FASEB J. 2008, 22, 1009-1020.)

The object of the present invention is to provide novel agents and the like that are useful for promoting DKK1 expression (increasing DKK1).

As a result of intensive research conducted by the inventors to achieve the above-mentioned object, they discovered that a specific plant (plant extract) is effective (useful) in promoting DKK1 expression (production) [and further, related to this, inhibiting pigmentation (and thus whitening)], and thus completed the present invention.

That is, the present invention relates to the following inventions, etc.
[1]
A DKK1 expression promoter comprising (particularly as an active ingredient) an extract of at least one plant selected from the group consisting of mint plants (mint plants of the Lamiaceae family), safflower plants, eyeshadow plants, Hibiscus plants and honeysuckle plants.
[2]
An agent for inhibiting pigmentation and/or whitening, comprising an extract of at least one plant selected from the group consisting of plants of the genus Mint, the genus Carthamus, the genus Eyelash, the genus Hibiscus, and the genus Honeysuckle.
[3]
The agent according to [1], which is used for inhibiting pigmentation and/or whitening.
[4]
The agent according to any one of [1] to [3], which contains at least an extract of a mint plant.
[5]
The agent according to any one of [1] to [4], wherein the Mint plant includes bergamot mint (e.g., bergamot mint), the Carthamus plant includes safflower (e.g., safflower), the Eyebright plant includes eyebright (e.g., eyebright), the Hibiscus plant includes hibiscus (roselle) (e.g., hibiscus), and the Honeysuckle plant includes honeysuckle (e.g., honeysuckle).
[6]
The agent according to any one of [1] to [5], comprising at least an extract of a plant of the genus Mint and an extract of a plant of the genus Carthamus.
[7]
The agent according to any one of [1] to [6], comprising at least an extract of a Mint plant and an extract of a Carthamus plant, wherein the Mint plant comprises bergamot mint (e.g., bergamot mint), and the Carthamus plant comprises safflower (e.g., safflower).
[8]
The agent according to any one of [1] to [7], comprising at least an extract of a plant of the genus Mint and an extract of a plant of the genus Safflower, wherein the ratio of the extract of the plant of the genus Safflower is 0.05 to 200 parts by mass (e.g., 0.1 to 100 parts by mass) per 1 part by mass of the extract of the plant of the genus Mint.
[9]
The agent according to any one of [1] to [8], comprising at least an extract of a plant of the genus Mint and an extract of a plant of the genus Safflower, wherein the ratio of the extract of the plant of the genus Safflower is 0.5 parts by mass or more (e.g., 1 part by mass or more) per 1 part by mass of the extract of the plant of the genus Mint.
[10]
The agent according to any one of [1] to [9], comprising at least an extract of a plant of the genus Mint and an extract of a plant of the genus Safflower, wherein the ratio of the extract of the plant of the genus Safflower is 0.5 to 100 parts by mass (e.g., 1 to 20 parts by mass) per 1 part by mass of the extract of the plant of the genus Mint.
[11]
The agent according to any one of [1] to [10], comprising at least an extract of a plant of the genus Mint and an extract of a plant of the genus Safflower, wherein the ratio of the extract of the plant of the genus Safflower is 0.5 to 1.5 parts by mass (e.g., 0.8 to 1.2 parts by mass) or 7 to 30 parts by mass (e.g., 10 to 20 parts by mass) per part by mass of the extract of the plant of the genus Mint.
[12]
A composition for promoting DKK1 expression, comprising an extract of at least one plant selected from the group consisting of Mint, Carthamus, Eyelash, Hibiscus, and Honeysuckle.
[13]
A composition for inhibiting pigmentation and/or whitening, comprising an extract of at least one plant selected from the group consisting of mint, safflower, eyeshadow, hibiscus and honeysuckle.
[14]
The composition according to [12] or [13], which is a cosmetic.
[15]
The agent or composition according to any one of [1] to [14], wherein DKK1 comprises DKK1 in fibroblasts (for promoting DKK1 expression in fibroblasts).

The present invention provides novel agents and the like that are useful for promoting DKK1 expression (increasing DKK1).

[Agent]
The present invention provides an agent containing (containing as an active ingredient) an extract of at least one plant selected from mint (Mentha), safflower (Carthamus), eyeflower (Euphrasia), Hibiscus, and honeysuckle (Lonicera).

Examples of plants in the genus Mint (family Lamiaceae, genus Mint) include peppermint and spearmint.

Specific examples of mint plants include bergamot mint (bergamot mint, orange mint), peppermint (peppermint), Japanese mint, spearmint, apple mint, pineapple mint, cat mint, pennyroyal mint, mentha piperita, water mint, corn mint, Asian mint, Australian mint, Heart's pennyroyal mint, Taiwan mint, forest mint, horse mint, Corsican mint, ginger mint, Kentucky kernel mint, grapefruit mint, etc.

Mint plants may be used alone or in combination of two or more species.

Of these, bergamot mint is particularly preferred. Therefore, the mint plant may contain at least bergamot mint.

Examples of plants in the genus Carthamus (Asteraceae family, Carthamus tinctorius) include safflower, carthamus tinctorius, etc.

Safflower plants may be used alone or in combination of two or more species.

Among these, safflower is particularly preferred. Therefore, a plant of the genus Carthamus may include at least safflower.

Examples of plants in the genus Euonymus (family Scrophulariaceae, genus Euonymus) include Euonymus quinquefolius, such as eyebright (Euonymus quinquefolius).

Plants of the genus Euonymus may be used alone or in combination of two or more species.

Among these, Brussels sieboldii (particularly eyebright) is particularly preferred. Therefore, a plant of the genus Brussels sieboldii may contain at least Brussels sieboldii (particularly eyebright).

Examples of plants in the genus Hibiscus (family Malvaceae, genus Hibiscus) include hibiscus (roselle), rose of Sharon, Japanese maple, Hamabo, Yuuna, and kenaf.

Plants of the genus Euonymus may be used alone or in combination of two or more species.

Among these, hibiscus is particularly preferred. Therefore, the Hibiscus plant may include at least hibiscus.

Examples of plants in the genus Lonicera (family Caprifoliaceae, Lonicera genus) include honeysuckle.

Of these, honeysuckle is particularly preferred. Therefore, a honeysuckle plant may contain at least honeysuckle.

In the extract, the part of the plant is not particularly limited, and a general part may be used for each plant. Specific parts that may be used include, for example, flowers, leaves, seeds (seeds, seed coats), stems, roots, etc., or a combination of these parts may be used, or the whole plant may be used.
Typically, at least the flowers and leaves may be used. The part of the plant may be selected depending on the type of plant. For example, at least the flowers may be used for hibiscus (roselle) and at least the leaves may be used for plants other than hibiscus.

Among plants, Mint, Carthamus, Eyelash, and Hibiscus are preferred in terms of promoting DKK1 expression.

Among these, mint plants and safflower plants are more preferred, with mint plants being especially preferred.

Therefore, the plant (plant extract) may contain at least such a plant (plant extract).

For example, the agent may preferably contain at least an extract of one plant selected from the mint, safflower, eyeshadow, and Hibiscus genus plants (more preferably, one selected from the mint and safflower plants, particularly a mint plant).

Plants (plant extracts) may be used alone or in combination of two or more types.

When using such combinations, it is particularly preferred to combine at least an extract of a mint plant [combine an extract of a mint plant with an extract of another plant and another extract (an extract of at least one plant selected from the group consisting of a safflower plant, an eyebrow plant, a Hibiscus plant, and a honeysuckle plant)], and it is particularly preferred to combine an extract of a mint plant with an extract of a safflower plant.

By combining in this way, it is possible to efficiently (e.g., synergistically) promote DKK1 expression.

When the plant extract contains a combination of an extract of a mint plant and an extract of another plant, the ratio of the extract of the mint plant to the total plant extract (ratio in terms of solid content) may be, for example, 0.01% by mass or more (e.g., 0.1% by mass or more), preferably 0.5% by mass or more (e.g., 1% by mass or more), more preferably 2% by mass or more (e.g., 3% by mass or more), and can also be 5% by mass or more (e.g., 8% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 40% by mass or more, 50% by mass or more, 60% by mass or more, 70% by mass or more, 80% by mass or more, 90% by mass or more), etc.

When the extract of a mint plant is combined with an extract of another plant, the ratio of the extract of the mint plant to the total plant extract (ratio calculated as solid content) may be, for example, 99.99% by mass or less (e.g., 99.9% by mass or less), 99.5% by mass or less (e.g., 99% by mass or less), 98% by mass or less (e.g., 97% by mass or less), 95% by mass or less (e.g., 92% by mass or less), 90% by mass or less (e.g., 85% by mass or less), 80% by mass or less (e.g., 75% by mass or less), 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, etc.

In addition, when the plant extract contains (at least contains) an extract of a mint plant and an extract of a safflower plant, the proportion of the extract of the safflower plant (proportion in terms of solid content) may be selected from a range of, for example, about 0.001 parts by mass or more (e.g., 0.005 parts by mass or more) relative to 1 part by mass of the extract of the mint plant, and may be 0.01 parts by mass or more (e.g., 0.03 parts by mass or more), preferably 0.05 parts by mass or more (e.g., 0.1 parts by mass or more), more preferably 0.2 parts by mass or more (e.g., 0.3 parts by mass or more), particularly 0.5 parts by mass or more (e.g., 0.8 parts by mass or more), or may be 1 part by mass or more (e.g., more than 1 part by mass, 1.2 parts by mass or more, 1.5 parts by mass or more, 2 parts by mass or more, 3 parts by mass or more, 5 parts by mass or more, 6 parts by mass or more, 7 parts by mass or more, 8 parts by mass or more, 9 parts by mass or more, 10 parts by mass or more), etc.

When the plant extract contains (at least contains) an extract of a mint plant and an extract of a safflower plant, the proportion of the extract of the safflower plant (proportion in terms of solid content) may be selected from a range of, for example, about 10,000 parts by mass or less (e.g., 5,000 parts by mass or less) relative to 1 part by mass of the extract of a mint plant, and may be 3,000 parts by mass or less (e.g., 2,000 parts by mass or less), preferably 1,000 parts by mass or less (e.g., 500 parts by mass or less), more preferably 300 parts by mass or less (e.g., 200 parts by mass or less), particularly 150 parts by mass or less (e.g., 120 parts by mass or less), or may be 100 parts by mass or less (e.g., 80 parts by mass or less, 50 parts by mass or less, 40 parts by mass or less, 35 parts by mass or less, 30 parts by mass or less, 25 parts by mass or less, 22 parts by mass or less, 20 parts by mass or less, 18 parts by mass or less, 15 parts by mass or less, 12 parts by mass or less), etc.

When the plant extract contains (at least contains) an extract of a plant of the Mint genus and an extract of a plant of the Safflower genus, it is easy to promote DKK1 expression in the ratios described above, but even within these ratios, there seem to be certain ratios that show exceptionally excellent DKK1 expression effects.

Therefore, the ratio of the extract of a mint plant to the extract of a safflower plant (ratio in terms of solid content) may be a more specific ratio, for example, the ratio of the extract of a safflower plant to 1 part by mass of the extract of a mint plant (ratio in terms of solid content) may be 0.05 to 200 parts by mass (e.g., 0.1 to 100 parts by mass), 0.5 parts by mass or more (e.g., 1 part by mass or more), 0.5 to 100 parts by mass (e.g., 1 to 20 parts by mass), 0.5 to 1.5 parts by mass (e.g., 0.8 to 1.2 parts by mass), 7 to 30 parts by mass (e.g., 10 to 20 parts by mass), etc.

Extracts can be commercially available products, or can be obtained by extracting plants (or plant parts).

In the extraction, the solvent (extraction solvent) can be selected depending on the type and the part or portion of the plant to be used, and examples thereof include water, alcohols [e.g., alkanols (e.g., C _1-4 alkanols such as methanol, ethanol, isopropanol, and n-butanol), polyols (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, etc.), and esters (e.g., ethyl acetate, etc.).
The extraction solvents may be used alone or in combination of two or more.

Typical extraction solvents include water, alcohols (such as ethanol), and mixtures of these.

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

There are no particular limitations on the extraction temperature or time, and these can be selected appropriately depending on the extraction solvent and extraction method.

When extracting, the plant may be subjected to appropriate treatment (such as crushing, heating, or drying) as necessary. The extract may also be further concentrated or dried (such as drying at room temperature or freeze-drying).

The form of the extract in the agent (and further in the composition described below) is not particularly limited, and may be, for example, a liquid (e.g., an extract containing an extraction solvent) or a powder (or granular powder).

(Use of the agent)
The agent of the present invention can be used for specific purposes.

First, the agent of the present invention can be used as a DKK1 (Dickkopf-1) expression promoter [an agent for promoting (improving, enhancing, activating) the expression (production) of DKK1].
In particular, DKK1 may be human DKK1.

Therefore, the agent of the present invention can also be used for applications related (or reported to be related) to the promotion of DKK1 expression [e.g., as an agent for inhibiting pigmentation (e.g., pigmentation in the epidermis) and as a skin whitening agent].

The site of DKK1 (the site where DKK1 expression is promoted) is not particularly limited and may be any site of the subject of ingestion/administration (the subject of application of the agent), but examples include fibroblasts (dermal fibroblasts), keratinocytes (epidermal keratinocytes, keratinocytes), mesenchymal stem cells (stem cells derived from adipose tissue, etc.), etc.

In particular, the site of DKK1 may be at least the skin (epidermis, dermis, subcutaneous tissue, adipose tissue, etc.).

These sites may be used alone or in combination to promote the expression of DKK1.

In particular, the agent of the present invention may be an agent for promoting the expression of DKK1 in the skin (epidermis, dermis, subcutaneous tissue, adipose tissue, etc.) (further, an agent for inhibiting pigmentation associated with the promotion of DKK1 expression in the skin, and an agent for whitening associated with the promotion of DKK1 expression in the skin).

The agent of the present invention may also be used as an agent for a specific application, such as for medicine, food and beverages, cosmetics, etc.

[Composition]
The present invention also includes a composition comprising the agent [or an extract of at least one plant selected from the group consisting of plants of the genus Mint, the genus Carthamus, the genus Brussels sapwood, the genus Hibiscus, and the genus Honeysuckle].

In this composition, the form (specific form, preferred form, etc.) of the agent [or an extract of at least one plant selected from the group consisting of plants of the genus Mint, the genus Carthamus, the genus Brussels sapwood, the genus Hibiscus, and the genus Honeysuckle] is the same as that described above.

Such compositions can also be used for the same functions and purposes as the above-mentioned agents. For example, they can be used to promote DKK1 (Dickkopf-1) expression, inhibit pigmentation, and whiten the skin.

In addition, such functions and uses may be those that, like the above-mentioned agents, contain as an active ingredient an extract of at least one plant selected from the mint genus (mentha genus), safflower genus, eyeshadow genus, Hibiscus genus, and honeysuckle genus.

The composition may also be used for pharmaceutical, food and beverage, cosmetic, etc.

In particular, the composition of the present invention may be suitably used as a cosmetic (composition for cosmetic use) from the viewpoint of having a DKK1 expression promoting effect, and furthermore (related to the DKK1 expression promoting effect) a pigmentation inhibitory effect and a skin whitening effect. The cosmetic composition is not particularly limited, and may be classified as a quasi-drug, such as medicated cosmetics, according to the definition of the Pharmaceutical Affairs Law.

The composition of the present invention only needs to contain the agent (an extract of at least one plant selected from the group consisting of plants of the genus Mint, the genus Carthamus, the genus Brussels sapwood, the genus Hibiscus, and the genus Honeysuckle), and may contain other ingredients depending on the intended use, form, etc.

Such other ingredients (ingredients that are not extracts of at least one plant selected from the group consisting of Mint, Carthamus, Brussels spp., Hibiscus, and Honeysuckle) include bases or carriers, additives, other active ingredients, etc. Note that such other ingredients and their proportions can be appropriately selected depending on the form, properties, etc. of the composition.

The base or carrier is not particularly limited, but examples thereof include hydrocarbons such as paraffin, liquid paraffin, squalane, white wax, gelling hydrocarbons (such as Plastibase), ozokerite, ceresin, petrolatum, hard fat, microcrystalline wax, α-olefin oligomers, and light liquid paraffin; fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and isostearic acid; tri-fatty acid glycerides such as glyceryl tri-2-ethylhexanoate (trioctanoin) and tri(caprylic acid/capric acid)glyceryl; higher alcohols such as cetanol, stearyl alcohol, and behenyl alcohol; methylpolysiloxane, highly polymerized methylpolysiloxane, dimethylsiloxane-methyl(polyoxyethylene)siloxane-methyl(polyoxypropylene)siloxane copolymer, dimethylsiloxane-methyl(polyoxyethylene)siloxane copolymer, dimethylsiloxane-methyl(polyoxypropylene)siloxane copolymer, polyoxyethylene - Silicone oils such as methylpolysiloxane copolymer, poly(oxyethylene-oxypropylene)-methylpolysiloxane copolymer, dimethylsiloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstearoxysiloxane copolymer, alkyl acrylate copolymer methylpolysiloxane ester, crosslinked methylpolysiloxane, crosslinked methylphenylpolysiloxane, crosslinked polyether modified silicone, crosslinked alkylpolyether modified silicone, crosslinked alkyl modified silicone, decamethylcyclopentasiloxane, ethyltrisiloxane, methyltrimethicone, methylsiloxane network polymer, polyoxyethylene-methylpolysiloxane copolymer, methylhydrogenpolysiloxane, triethoxysilylethyl polydimethylsiloxyethylhexyldimethicone, and dimethylpolysiloxane; ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, and hexylene glycol diacetate. glycol acetates such as 2-methyl-2-propene-1,1-diol diacetate; glycol esters such as triethylene glycol divalerate, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, and 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, and hydroxypropyl methyl cellulose; polyvinylpyrrolidone; carrageenan; Examples of the bases or carriers include polyvinyl butyrate, polyethylene glycol, dioxane, butylene glycol adipic acid polyester, esters such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythritol tetra 2-ethylhexanoate, polysaccharides such as dextrin and maltodextrin, lower alcohols such as ethanol and 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, and dipropylene glycol monopropyl ether, and aqueous bases such as water. These bases or carriers can be used alone or in combination of two or more.

Additives are not particularly limited, but examples thereof include antioxidants, surfactants, thickeners, preservatives, pH adjusters, stabilizers, preservatives, colorants, and fragrances. These additives can be used alone or in combination of two or more.

Examples of antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivatives (such as ascorbic acid phosphate), tocopherol, tocopherol derivatives, erythorbic acid, and L-cysteine hydrochloride.

Examples of surfactants include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexyl acid, and diglycerol sorbitan tetra-2-ethylhexyl acid; propylene glycol fatty acid esters such as propylene glycol monostearate; glycerin alkyl ethers; alkyl glucosides; amines such as stearylamine and oleylamine; silicone surfactants such as polyoxyethylene-methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone.

Examples of thickeners include guar gum, locust bean gum, carrageenan, xanthan gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, acrylate/methacrylate alkyl copolymer, polyethylene glycol, bentonite, alginic acid, macrogol, and cellulose-based thickeners (methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, etc.) and salts thereof.

Examples of preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, phenoxyethanol, benzyl alcohol, chlorobutanol, sorbic acid and its salts, chlorhexidine gluconate, alkanediols, and glycerin fatty acid esters.

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

Examples of stabilizers include sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole, edetate, etc.

Other active ingredients include, but are not limited to, moisturizing ingredients, anti-inflammatory ingredients, antibacterial or germicidal ingredients, vitamins, peptides or their derivatives (esters, amides, etc.), cell activating ingredients, anti-aging ingredients, blood circulation promoting ingredients, keratin softening ingredients, whitening ingredients, astringent ingredients, etc. These active ingredients can be used alone or in combination of two or more.

Examples of moisturizing ingredients include polymeric 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 phospholipids; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and perilla extract.

Anti-inflammatory ingredients include, for example, 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, etc.

Examples of antibacterial or germicidal ingredients 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, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride, chlorhexidine gluconate, zinc paraphenolsulfonate, etc.

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

Examples of peptides or derivatives thereof include keratin hydrolyzed peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin hydrolyzed peptides, collagen hydrolyzed peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin hydrolyzed peptides, conchiolin hydrolyzed peptides, hydrolyzed conchiolin, silk proteolytic peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soybean proteolytic peptides, hydrolyzed soybean protein, wheat protein, wheat proteolytic peptides, hydrolyzed wheat protein, casein hydrolyzed peptides, acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.), etc.

Examples of cell activation ingredients include vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids; α-hydroxy acids such as glycolic acid and lactic acid; tannins, flavonoids, saponin, allantoin, and photosensitizer No. 301.

Anti-aging ingredients include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, etc.

Examples of blood circulation-promoting ingredients include ingredients derived from plants (e.g., ginseng, angelica, arnica, ginkgo, fennel, emmeisou, Dutch oak, chamomile, Roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake mushroom, European hawthorn, European juniper, cnidium rhizome, swertia britannica, thyme, clove, tangerine peel, angelica tree, peach kernel, spruce, carrot, garlic, butcher's broom, grape, peony, horse chestnut, melissa, yuzu, coix seed, rosemary, rose hip, peach, apricot, walnut, corn); glucosyl hesperidin, etc.

Examples of keratin softening ingredients include salicylic acid, glycolic acid, fruit acid, phytic acid, sulfur, etc.

Examples of whitening ingredients include ascorbic acid and its derivatives (phosphate esters, etc.), arbutin, tocopherol, etc.

Examples of astringent ingredients include zinc paraphenolsulfonate, zinc oxide, menthol, and ethanol.

The form of the composition of the present invention is not particularly limited and can be appropriately selected depending on the application, etc. Examples of the form include liquid, fluid, semi-solid, etc.
The form of the composition of the present invention (e.g., cosmetic composition) is not particularly limited, and examples thereof include liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, aerosols, sheets in which nonwoven fabric is impregnated with a drug solution, etc. Among these, preferred are liquids, suspensions, emulsions, creams, etc.

Specific uses of the composition of the present invention are not particularly limited, but examples thereof include basic cosmetics such as lotions, cosmetic milky lotions, cosmetic oils, gels, creams, beauty serums, sunscreen cosmetics, packs, masks, hand creams, body lotions, and body creams; cleansing cosmetics such as face washes, makeup removers, body shampoos, shampoos, rinses, and treatments; makeup cosmetics such as makeup bases, foundations, face powders, water-based powders, powders, grease guns, eye shadow bases, eye shadows, nose shadows, lip pencils, lipsticks, lip glosses, blushers, and various colors; hair care products such as shampoos, dry shampoos, conditioners, rinses, rinse-in shampoos, treatments, hair tonics, hair styling products, hair oils, pomades, and hair coloring agents; dentifrices, lip balms, soaps, and body soaps.
Among these, preferred are lotions, cosmetic emulsions, cosmetic oils, gels, creams, beauty essences, sunscreen cosmetics, etc., and more preferred are lotions, cosmetic emulsions, creams, beauty essences, etc.

Specific uses of the composition of the present invention when it is a quasi-drug are not particularly limited, but examples include medicated cosmetics, medicated soaps, medicated dentifrices, antiperspirants, medicated creams, hair restorers, hair dyes, mouthwashes, energy drinks, mouth fresheners, contact lens wearers, germicides, disinfectants, chilblains, digestive aids, herbal medicine-containing health medicines, vitamin-containing health medicines, bath additives, etc. Among these, medicated cosmetics, medicated creams, hair restorers, etc. are preferred.

The method for producing the composition of the present invention is not particularly limited as long as it uses the agent of the present invention (an extract of at least one plant selected from the group consisting of plants of the genus Mint, the genus Carthamus, the genus Brussels sapwood, the genus Hibiscus, and the genus Honeysuckle), and any conventionally known method can be used depending on the application and properties of the composition. For example, the composition can be produced by blending the agent of the present invention as it is or after emulsification, solubilization, or dispersion during the production of the composition by a conventional method.

In the composition of the present invention, the proportion of the agent of the present invention (an extract of at least one plant selected from mint plants, safflower plants, eyebrows, Hibiscus plants, and honeysuckle plants) can be appropriately selected depending on the type of composition and the ingredients used, and is not particularly limited. For example, the proportion of the extract of at least one plant selected from mint plants, safflower plants, eyebrows, Hibiscus plants, and honeysuckle plants (proportion converted into solid content) may be, for example, 0.00001 mass% or more, preferably 0.0001 mass% or more, and more preferably 0.001 mass% or more.
The upper limit of the proportion (proportion converted into solid content) of the extract of at least one plant selected from the group consisting of Mint, Carthamus, Houttuynia, Hibiscus, and Honeysuckle is not particularly limited, and may be, for example, 0.0001 mass%, 0.0003 mass%, 0.001 mass%, 0.003 mass%, 0.01 mass%, 0.03 mass%, 0.05 mass%, 0.1 mass%, 0.3 mass%, 0.5 mass%, 1 mass%, etc.

[Usage, etc.]
The present invention includes various methods using the agent or composition.
Such a method may be, for example, a method of using the agent or composition on a subject to be used (applied).

And such a method may be accompanied by the above-mentioned functions and actions (e.g., promoting DKK1 expression, inhibiting pigmentation, whitening).

The method of using (applying) the agent or composition of the present invention is not particularly limited and can be appropriately selected depending on the subject of use (application), etc. For example, when used as a cosmetic, the method can be appropriately selected depending on the skin condition, age, sex, etc., and for example, an appropriate amount (e.g., about 0.005 to 0.5 g) may be applied (sprayed, sprayed, pasted, etc.) to the skin several times a day (e.g., 1 to 5 times a day, preferably 1 to 3 times a day). It can also be applied to any skin, such as the face, neck, hands, feet, fingers, trunk, scalp, etc.

The amount of the agent or composition of the present invention to be used (applied) is also not particularly limited and may vary appropriately depending on the type and components of the composition, but may be, for example, 0.0001 to 100 mg/cm 2 (skin area), preferably 0.001 to 10 mg/cm ² (skin area) per day for an adult, as a proportion (converted into solid content) of an extract of at least one plant selected from plants of the genus Mint, genus Carthamus, genus ^Brussels spp., genus Hibiscus, and genus Honeysuckle.

The present invention will be described in detail below with reference to examples, but the present invention is not limited to these.

[Extract production]
40 g of dried bergamot mint leaves were powdered in a mixer, and then 20 times the amount of 90% ethanol (aqueous ethanol solution) was added and stirred overnight for extraction. The solvent of the resulting extract was removed using an evaporator, and the resulting suspension was resuspended in water and freeze-dried to obtain a bergamot mint extract powder.

Each plant extract was prepared in the same manner. Dried flowers were used for hibiscus (roselle), and dried leaves were used for the other plants.

[test]
Human newborn normal skin fibroblasts (manufactured by Toyobo Co., Ltd.) were cultured in DMEM medium containing 10% by volume of FBS, and the cells were then harvested by trypsinization.
The cells were seeded in a 6-well plate to a cell density of 7.5 x ¹⁰ cells/well and cultured overnight at 37°C and 5% by volume _CO2 . After culture, the medium was removed and replaced with medium containing the test sample extract at the concentration shown in the table, and cultured for 24 hours.
As a control, the cells were cultured in the same manner using a medium containing only DMSO, which was used as a dilution solvent for the test sample extract.
After the culture, the medium was removed, total RNA was extracted with TRIzol (Thermo Fisher), the amount of each RNA was measured with a spectrophotometer, and total RNA was adjusted to 100 ng/μL.

Using this total RNA as a template, cDNA was synthesized by reverse transcriptase, and then the cDNA was used as a template to measure the expression levels of mRNA for DKK1 and β-actin as an internal standard.
Detection was performed by RT-PCR reaction using a real-time PCR device (manufactured by Bio-Rad) and a TaKaRa SYBR PrimeScript RT-PCR kit (Perfect Real Time) (manufactured by Takara Bio).
The expression level of DKK1 mRNA was calculated based on the total RNA samples prepared from cells cultured with and without the addition of the test sample extract, and was corrected with the β-actin value.

From the obtained values, the DKK1 mRNA expression promotion rate (%) was calculated using the following formula.

DKK1 mRNA expression promotion rate (%) =
(Test sample extract DKK1 mRNA expression level/control DKK1 mRNA expression level)×100

Specific examples of formulations of compositions containing the agent of the present invention are given below.

Formulation Example 1: Lotion A lotion having the following composition is prepared according to the following preparation method.
The following ingredients are formulated so that the total is 100% by weight. All ingredients are mixed and stirred at room temperature to obtain a homogeneous solution, and the pH is adjusted to 5.5 to obtain a lotion.
Ingredients Weight %
Concentrated glycerin 4.0
Sorbitol 4.0
Sodium citrate 0.3
Polyoxyethylene hydrogenated castor oil 0.5
Bergamot mint extract 0.01
Ethanol 15.0
Fragrance 0.005
Citric acid Appropriate amount Purified water Remainder

Formulation Example 2: Facial Cleansing Cream A facial cleansing cream having the following composition is prepared according to the following preparation method.
Components A to C are formulated in the following proportions so that the total of components A, B and C is 100% by weight. First, the mixture of component A is heated and dissolved, and maintained at 80°C. Next, the mixture of component B, which has been separately heated and dissolved at 80°C, is added to the mixture of component A and thoroughly stirred. After that, the mixture is cooled with stirring, and the mixture of component C is added at 50°C to obtain a facial cleansing cream.
"Component A"
Ingredients Weight %
Myristic acid 14.0
Stearic acid 12.0
Lauric acid 3.5
Oleyl alcohol 1.5
Coconut oil fatty acid amidopropyl betaine 10.5
"Component B"
Ingredients Weight %
Concentrated glycerin 18.0
Potassium hydroxide 7.0
Paraoxybenzoic acid ester Appropriate amount of purified water Remainder "Component C"
Ingredients Weight %
Bergamot mint extract 0.01
Fragrance (appropriate amount)

Formulation Example 3: Milky Lotion A milky lotion having the following composition is prepared according to the following preparation method.
Components D to F are formulated in the following proportions so that the total of components D, E and F is 100% by weight. First, the component D mixture is heated and dissolved, and maintained at 80°C. Next, the component E mixture, which has been separately heated and dissolved at 80°C, is added to the component D mixture and thoroughly stirred. After that, the mixture is cooled with stirring, and the component F mixture is added at 50°C to obtain an emulsion.
"Component D"
Ingredients Weight %
Sucrose fatty acid ester 1.0
Carboxyvinyl polymer 0.06
Potassium hydroxide 0.028
Paraoxybenzoic acid ester Appropriate amount of purified water Remaining "ingredient E"
Ingredients Weight %
Olive oil 4.0
Jojoba oil 4.0
Myristyl lactate 2.0
Self-emulsifying glyceryl monostearate 1.5
Lipophilic glyceryl monostearate 1.5
"Component F"
Ingredients Weight %
Bergamot mint extract 0.01
Fragrance 0.2

The agent of the present invention can be used as a DKK1 expression promoter, etc.

Claims (12)

A DKK1 expression promoter comprising an extract of at least one plant selected from the group consisting of mint, safflower, eyeshadow, Hibiscus, and honeysuckle. The agent according to claim 1, which contains at least an extract of a mint plant. The agent according to claim 1 or 2, wherein the Mint plant includes bergamot mint, the Carthamus plant includes safflower, the Eyebright plant includes eyebright, the Hibiscus plant includes roselle, and the Honeysuckle plant includes honeysuckle. The agent according to claim 1 or 2, which contains at least an extract of a plant of the genus Mint and an extract of a plant of the genus Carthamus. The agent according to claim 1 or 2, which contains at least an extract of a plant of the genus Mint and an extract of a plant of the genus Carthamus, the plant of the genus Mint containing bergamot mint, and the plant of the genus Carthamus containing safflower. The agent according to claim 1 or 2, which contains at least an extract of a plant of the genus Mint and an extract of a plant of the genus Safflower, and the ratio of the extract of the plant of the genus Safflower is 0.05 to 200 parts by mass per 1 part by mass of the extract of the plant of the genus Mint. The agent according to claim 1 or 2, which contains at least an extract of a plant of the genus Mint and an extract of a plant of the genus Safflower, and the ratio of the extract of the plant of the genus Safflower to 1 part by mass of the extract of the plant of the genus Mint is 0.5 parts by mass or more. The agent according to claim 1 or 2, which contains at least an extract of a plant of the genus Mint and an extract of a plant of the genus Safflower, and the ratio of the extract of the plant of the genus Safflower is 0.5 to 100 parts by mass per 1 part by mass of the extract of the plant of the genus Mint. The agent according to claim 1 or 2, which contains at least an extract of a plant of the genus Mint and an extract of a plant of the genus Safflower, and the ratio of the extract of the plant of the genus Safflower to 1 part by mass of the extract of the plant of the genus Mint is 0.5 to 1.5 parts by mass or 7 to 30 parts by mass. A composition for promoting DKK1 expression, comprising an extract of at least one plant selected from the group consisting of mint, safflower, eyeshadow, Hibiscus, and honeysuckle. The composition according to claim 10, which is a cosmetic. The agent or composition according to claim 1 or 10, wherein the DKK1 comprises DKK1 in fibroblasts.