JP6830000B2 - Composition for suppressing pheomelanin - Google Patents

Description

The present invention relates to a composition for suppressing pheomelanin.

Melanin is a pigment produced in melanosomes in melanocytes (melanocytes) present in tissues such as skin and hair. Melanin is roughly classified into two types, black eumelanin and reddish brown to yellow pheomelanin. When eumelanin is formed and deposited on the skin, black pigmentation, increased dullness, decreased transparency, and the like occur, resulting in impaired cosmetology.

The synthesis of melanin is via the synthesis of tyrosine to dopa and then dopa to dopaquinone by the action of tyrosinase. Further, eumelanin is synthesized from dopaquinone via dopachrome, and instead pheomelanin is synthesized through the binding of dopaquinone to cysteine, glutathione, etc. (see Non-Patent Document 1).

Focusing on such melanin synthesis, pheomelanin production promoters and glutathione production promoters for increasing the pheomelanin / eumelanin ratio are known as those for preventing the formation and deposition of eumelanin (). For example, see Patent Documents 1 and 2).

On the other hand, pheomelanin is known to have cytotoxic properties such as increased oxidative stress and decreased activity of in vivo antioxidants (see Non-Patent Documents 2 and 3). In particular, since it is known that the onset of melanoma tends to be induced in a mouse with a high expression of pheomelanin, the effect of pheomelanin on the human body extends to all life phenomena, not only life and death but also life. It can be said that it is closely related to quality (QOL) (see Non-Patent Document 4).

Patent No. 5663141 Japanese Unexamined Patent Publication No. 2012-51837

Furumura M, et al., Pigment Cell Res., 1996, 9, pp.191-203 Napolitano A et al., Pigment Cell Melanoma Res., 2014, Sep; 27 (5), pp.721-733 Panzella L et al., Pigment Cell Melanoma Res., 2014, Mar; 27 (2), pp.244-252 Devarati Mitra et al., Nature, 2012, 491 (7424), pp.449-453

Certainly, according to the agents described in Patent Documents 1 and 2, there is a possibility that the formation of eumelanin can be inhibited. However, since these drugs increase the amount of pheomelanin synthesized instead, there is a problem that they may have an adverse effect on the human body.

Therefore, if it is possible not only to reduce the amount of pheomelanin but also to reduce the ratio of the amount of pheomelanin to the total amount of pheomelanin composed of pheomelanin and eumelanin, it is possible to avoid cell damage and adverse effects on the human body. Will be. However, to date, few drugs or active ingredients have been known that effectively reduce the amount and proportion of pheomelanin in the total amount of melanin.

Therefore, the problem to be solved by the present invention is to provide a composition capable of not only reducing the amount of pheomelanin but also reducing the ratio of the amount of pheomelanin to the total amount of melanin. And.

In an attempt to solve the above problems, the present inventors have attempted to search for a substance that may have an action of reducing the amount of pheomelanin. In general, innumerable substances having a physiological action are known. Also, even if limited to those known as whitening agents, placenta extract, glutathione, yukinoshita extract, oil-soluble licorice extract, retinoid, ascorbic acid, ascorbic acid derivative, arbutin, kojic acid, vitamin E, tranexamic acid. , Cysteine, chamomile extract, linoleic acid, ellagic acid, rucinol, α-hydroxy acid, etc. are known, and each of them has a specific mechanism of action. In spite of this situation, the present inventors have finally found that ascorbic acid derivatives such as L-ascorbic acid 2-glucoside have an action of reducing the amount of pheomelanin through repeated studies. Moreover, the present inventors have found that the ascorbic acid derivative can not only reduce the amount of pheomelanin but also reduce the ratio of the amount of pheomelanin to the total amount of melanin.

On the other hand, according to the facts found by the present inventors, among the substances that can be used as whitening agents mentioned above, hydroquinone derivatives such as arbutin reduce the total amount of melanin while reducing the total amount of melanin, while pheno. There was no substantial reduction in the proportion of melanin content. In view of these facts, the action of the ascorbic acid derivative to reduce the proportion of the amount of pheomelanin is surprising and was first discovered by the present inventors.

By further trial and error, the present inventors synergistically use ascorbic acid derivatives and hydroquinone derivatives such as arbutin, whose action of reducing the proportion of pheomelanin alone cannot be confirmed. It has been found that the proportion of the amount of melanin can be reduced. Considering the result that the action of reducing the amount of pheomelanin by using the ascorbic acid derivative and the hydroquinone derivative in combination is additive, the ratio of the amount of pheomelanin by the combination of the ascorbic acid derivative and the hydroquinone derivative is determined. The result of synergistic reduction is very surprising and is also the first to be found by the present inventors.

Based on such findings, the present inventors have a composition having a pheomelanin inhibitory effect, which contains ascorbic acid, an ascorbic acid derivative and / or a salt thereof, and hydroquinone, a hydroquinone derivative and / or a salt thereof. I succeeded in creating a thing. The present invention is an invention completed based on these findings and successful examples.

Therefore, according to one aspect of the present invention, there is provided a pheomelanin-suppressing composition containing a first component selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof.

According to another aspect of the present invention, a first component selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof, and a second component selected from the group consisting of hydroquinone, hydroquinone derivatives and salts thereof. A composition for suppressing pheomelanin containing an ingredient is provided.

Preferably, the first component is a component selected from the group consisting of ascorbic acid, sodium ascorbic acid, ascorbic acid glucoside, ascorbic acid phosphate ester, ascorbic acid sulfate ester, ascorbic acid fatty acid ester and ascorbic acid alkyl ether. ..

Preferably, the second component is a substituted or unsubstituted hydroquinone-sugar condensate.

Preferably, the second component is arbutin.

Preferably, the composition for suppressing pheomelanin has a mass ratio (first component: second component) of the first component and the second component to be 1: 0.005-2. contains.

According to another aspect of the present invention, there is provided a composition for use in cosmetics or quasi-drugs, which contains the composition of one aspect of the present invention.

According to the composition for suppressing pheomelanin, which is one aspect of the present invention, not only the amount of pheomelanin can be reduced, but also the ratio of the amount of pheomelanin to the total amount of melanin can be reduced.

In addition, since the first component and the second component in the pheomelanin-suppressing composition, which is one aspect of the present invention, have been used in the human body as cosmetic components and the like, they are daily and safe for the user. It can be expected to be used for.

According to the composition for use in cosmetics and quasi-drugs, which is one aspect of the present invention, it can be widely and widely used according to each usage mode. For example, the cosmetic composition and the composition for non-pharmaceutical products, which are one aspect of the present invention, can be used by taking various aspects such as a lotion, a beauty essence, a beauty essence, a whitening liquid, a milky lotion, and a cream. On the other hand, while reducing the cytotoxicity and adverse effects on the human body based on pheomelanin, cell protection effect, anti-aging effect (anti-aging), antioxidant effect, radical scavenging effect, skin quality maintenance effect, skin quality improvement effect, It can be expected to bring about physiological effects such as a whitening effect, a lightening of the skin color, a lightening of the skin color, and a uniform skin color improving effect.

FIG. 1 is a diagram showing the results of evaluating the amount of eumelanin and the amount of pheomelanin per cell using the test solutions of Examples 1 to 3 and the control as described in Examples described later. The numerical value directly above each bar graph indicates the amount of pheomelanin. FIG. 2 is a diagram showing the results of evaluating the eumelanin ratio and the pheomelanin ratio using the test solutions of Examples 1 to 3 and the control as described in Examples described later. The numerical value directly above each bar graph indicates the pheomelanin ratio. FIG. 3 is a diagram showing the results of evaluating the amount of eumelanin and the amount of pheomelanin per cell using the test solutions of Examples 2, Examples 4 to 6, and the control as described in Examples described later. is there. The numerical value directly above each bar graph indicates the amount of pheomelanin. FIG. 4 is a diagram showing the results of evaluating the eumelanin ratio and the pheomelanin ratio using the test solutions of Examples 2, Examples 4 to 6, and the control as described in Examples described later. The numerical value directly above each bar graph indicates the pheomelanin ratio.

Hereinafter, the details of the composition which is one aspect of the present invention will be described, but the technical scope of the present invention is not limited to the matters of the present item, and the present invention varies as long as the object is achieved. Can be taken.

The composition of one aspect of the present invention contains at least a first component selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof. The composition of another aspect of the present invention comprises a first component selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof, and a second component selected from the group consisting of hydroquinone, hydroquinone derivatives and salts thereof. At least contains the components of. In the present specification, these are collectively referred to as "composition of one aspect of the present invention". Further, in the present specification, only the first component and the combination of the first component and the second component may be collectively referred to as "useful component".

The composition of one aspect of the present invention is a composition for suppressing pheomelanin. Although the technical scope of the present invention is not bound by any theory or speculation, the composition of one aspect of the present invention not only reduces the amount of pheomelanin by containing useful ingredients, but also reduces the amount of pheomelanin. It is possible to reduce the ratio of the amount of pheomelanin to the total amount of melanin consisting of the amount of pheomelanin and the amount of eumelanin. In addition to the action of suppressing the synthesis of pheomelanin, the composition of one aspect of the present invention may have an action of decomposing once synthesized pheomelanin and reducing the amount or ratio thereof.

In the present specification, "the inhibitory effect on the amount of pheomelanin" means the ratio of the amount of pheomelanin to the total amount of melanin consisting of the amount of pheomelanin and the amount of eumelanin while reducing the amount (absolute amount) of pheomelanin. It means the action of reducing (relative amount).

The first component is not particularly limited as long as it is ascorbic acid, an ascorbic acid derivative, a salt thereof, or a combination thereof. The ascorbic acid derivative is not particularly limited as long as it has the meaning usually known as having ascorbic acid as a basic skeleton, and for example, an ascorbic acid derivative known to have a physiological action and the like. Specific examples thereof include ascorbic acid glucoside, ascorbic acid phosphate ester, ascorbic acid sulfate ester, ascorbic acid fatty acid ester, and ascorbic acid alkyl ether. Considering the inhibitory effect on the amount of pheomelanin, ascorbic acid glucoside is preferable, and L-ascorbic acid 2-glucoside is more preferable. Examples of the salt of ascorbic acid include sodium ascorbic acid and the like. As the ascorbic acid salt or ascorbic acid derivative, one of the above-exemplified ones can be used alone, or two or more of them can be used in combination. In general, ascorbic acid derivatives such as ascorbic acid glucoside and salts of ascorbic acid such as sodium ascorbic acid can have the same physiological action as ascorbic acid by being present as ascorbic acid ions in the living body. It has been known.

More specific examples of the first component include ascorbic acid (BASF Japan), ascorbic acid (crystal) (DSM Nutritions), sodium ascorbyl (BASF Japan), sodium ascorbyl (crystal) (DSM). Ascorbic acid glucoside such as ascorbic acid 2-glucoside commercially available from Nutritions), Wako Pure Chemical Industries, and Hayashihara, 3-O-ethylascorbic acid such as "VC ethyl" (Nippon Seika), " Ascorbyl tetra2-hexyldecanoate such as "NIKKOL (registered trademark) VC-IP" (Nikko Chemicals), "NIKKOL (registered trademark) VC-PMg" (Nikko Chemicals) and "asporbic acid PM" (Showa Denko), etc. Ascorbyl palmitate magnesium phosphate; ascorbyl dipalmitate such as "NIKKOL (registered trademark) CP" (Nikko Chemicals); ascorbyl palmitate such as "L-ascorbic acid palmitin ester" (DSM Nutritions); "NIKKOL (registered) Disodium ascorbic acid sulfate such as "VC-SS" (Nikko Chemicals); ascorbyl phosphate such as "Stay C-50" (DSM Nutritions) and "L-ascorbyl sodium phosphate" (BASF Japan) Sodium; 3 sodium ascorbyl palmitate; ascorbyl palmitate such as "Aprecier (registered trademark) (APPS)" (Showa Denko); but not limited to these.

The second component is not particularly limited as long as it is a hydroquinone, a hydroquinone derivative, a salt thereof, or a combination thereof. The hydroquinone derivative is not particularly limited as long as it has the meaning generally known as having hydroquinone as a basic skeleton, and examples thereof include a hydroquinone derivative known to have a physiological action. Specific examples thereof include a condensate of a substituted or unsubstituted hydroquinone and a sugar. Examples of the sugar include D-glucose, D-galactosamine, D-mannose, D-tagatous, D-fructos, L-sorbose, D-psicos, and L-arabino. -Luce, D-xylose, D-ribose, D-xylrose, D-lyxose, D-librose, D-glucosamine, D-galactosamine, sialic acid, muramic acid, uronic acid, Examples include, but are not limited to, D-glucuronic acid, D-galacturonic acid, D-mannuronic acid, L-iduronic acid and the like. As the hydroquinone derivative, one of the above-exemplified ones can be used alone, or two or more of them can be used in combination. As the hydroquinone derivative, arbutin (hydroquinone-β-D-glucopyranoside; β-arbutin) and α-arbutin (hydroquinone-α-D-glucopyranoside) are preferable, and arbutin is more preferable, in view of the application results to the human body. In general, it is known that a hydroquinone derivative such as arbutin can have the same physiological action as hydroquinone but is more stable than hydroquinone.

More specific examples of the second component are commercially available from "Stable Sustained Release Hydroquinone SHQ" (Environmental Management Holdings, Inc.), Rhodia, Mitsui Chemicals, Eastman Chemical, and Shoyo Kako. Hydroquinone; Arbutin marketed by Iwase Cosfa, Nippon Seika, Mitsubishi Chemical, Wako Pure Chemical Industries; DSM Nutritions, α-Arbutin marketed by Ezaki Glico Foods, etc. However, it is not limited to these.

The content of the first component is not particularly limited as long as it has an inhibitory effect on the amount of pheomelanin, but is, for example, 0.03 to 10% (w / v) with respect to the total amount of the composition. , 0.05 to 6% (w / v), more preferably 0.1 to 2% (w / v), and even more preferably 0.5 to 2% (w / v). When the content of the first component is within these ranges, a good inhibitory effect on the amount of pheomelanin can be obtained, and a composition having further safety can be obtained.

The content of the second component is not particularly limited as long as it has an inhibitory effect on the amount of pheomelanin when combined with the first component, but for example, 0.001 to 10 with respect to the total amount of the composition. % (W / v), preferably 0.01 to 8% (w / v), more preferably 0.05 to 3% (w / v), and 0.1 to 3% (w / v). More preferred. When the content of the second component is within these ranges, a synergistic effect of suppressing the amount of pheomelanin with the first component can be obtained, and a composition having further safety can be obtained.

The contents of each of the first component and the second component are as described above, but the total amount and mass ratio of these are as long as the composition of one aspect of the present invention exhibits an inhibitory effect on the amount of pheomelanin. Not particularly limited. For example, the mass ratio of the first component and the second component (first component: second component) is 1: 0.001 to 10, and in order to obtain a good inhibitory effect on the amount of pheomelanin, It is preferably 1: 0.003 to 5, and more preferably 1: 0.005 to 2.

The composition of one aspect of the present invention is not particularly limited in the degree of the inhibitory effect on the amount of pheomelanin, but for example, the system containing the first component is compared with the system not containing the first component, or Regarding the system containing the first component and the second component, a system containing neither the first component nor the second component or a system containing only one of the first component and the second component is used. In comparison, the effect is such that the amount of pheomelanin is suppressed.

A specific embodiment of the composition of one aspect of the present invention is a composition containing the first component in an amount of 0.1 to 2% (w / v) with respect to the total amount of the composition; On the other hand, the first component is contained at 0.1 to 2% (w / v), the second component is contained at 0.05 to 3% (w / v), and the first component and A composition or the like in which the mass ratio of the second component (first component: second component) is 1: 0.003 to 5.

A composition containing a useful ingredient can be utilized as a composition for use in cosmetics or quasi-drugs by itself or by containing it in combination with other ingredients. Therefore, the composition of another aspect of the present invention is a composition for use in cosmetics or quasi-drugs containing at least a useful ingredient.

A preferred specific embodiment of the composition of one aspect of the present invention is a cosmetic composition. The cosmetic composition is not particularly limited as long as it is applied to the skin, and examples thereof include skin care cosmetics, makeup cosmetics, fragrance cosmetics, and body care cosmetics, and more specifically. Is a lotion, serum, beauty oil, whitening liquid, milky lotion, cream, foundation, sunscreen, lotion, pack, BB cream, face powder, hand cream, cleansing, face wash, cosmetic base, concealer, lipstick, eye shadow, Examples include eyeliner, eyebrow, lip, mascara, eye color, lipstick, and all-in-one cosmetics. The cosmetic composition exhibits an inhibitory effect on the amount of pheomelanin, and has a cytoprotective effect, an anti-aging effect (anti-aging), an antioxidant effect, a radical scavenging effect, a skin quality maintaining effect, a skin quality improving effect, a whitening effect and / or. More preferably, it is a lotion, a beauty essence, a beauty oil, a whitening liquid, a milky lotion and a cream, which are desired to exert a skin color improving effect.

The cosmetic composition may contain, in addition to the useful ingredients, other ingredients commonly used in cosmetics, as long as the problems of the present invention can be solved.

Other ingredients that can be usually used in cosmetics are not particularly limited, and for example, solvents such as water and organic solvents, oily ingredients, emulsifiers, moisturizers, refreshing agents, preservatives, chelating agents, pH adjusters, antioxidants, etc. Examples include whitening agents, solubilizers, vitamins, various other medicinal ingredients, powders, fragrances, and coloring materials. The contents of other ingredients that can be usually used in cosmetics can be appropriately set by those skilled in the art as long as they do not interfere with solving the problems of the present invention. Some of the other components are listed below, but these are examples only and are not limited.

Examples of the moisturizing agent include glycerin, butylene glycol (BG), polyethylene glycol, trehalose, glycyrrhizinic acid and its salt, hyaluronic acid and its salt, dipropylene glycol (DPG), diglycerin, 1,2-pentanediol, and serine. , Glycerol extract, locust bean gum, glycerin mono2-ethylhexyl ether, xylitol, martitol, maltose, sorbitol, glucose, fructose, hydrolyzed elastin, lactic acid and its salts, cyclodextrin, pyrrolidone carboxylic acid and its salts, etc. , One of these can be used alone or in combination of two or more. The content of the moisturizer is preferably about 0 to 15% by mass.

Examples of the oily component include neopentyl glycol dicaprate, triethylhexanoin, isopropyl palmitate, cetyl 2-ethylhexanoate, isononyl isononanoate, isotridecyl isononanoate, diisopropyl sebacate, pentaerythrityl tetra2-ethylhexaneate, and the like. Ester oils such as diethylhexyl succinate, alkylbenzoate with 12 to 15 carbon atoms; octyldodecanol, oleyl alcohol, isostearyl alcohol, hexyldecanol, 2-decyltetradecinol, monooleylglyceryl ether (ceracyl alcohol), cetearyl Higher alcohols such as alcohols, behenyl alcohols and setanols; silicone oils such as dimethylpolysiloxane, dimethylcyclopolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, higher alcohol-modified silicone oils; liquid paraffins, light isoparaffins, squalanes, squalanes, etc. Linear and branched hydrocarbon oils such as Vaseline; higher fatty acids such as undecyleneic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, icosapentaenoic acid (EPA), docosahexaenoic acid (DHA), isostearic acid; acetglyceryl , Glyceryl triisooctanoate, glyceryl triethylhexanate, glyceryl triisostearate, glyceryl triisopalmitate, glyceryl monostearate, glyceryl di-2-heptyl undecanoate, glyceryl trimyristate, glyceryl tri2-ethylhexaneate, etc. Glyceride oil; vegetable oils such as jojoba oil, olive oil, nobara oil, soybean oil, orange flower oil, chamomile flower oil, lavender oil; animal oils such as liquid lanolin, sala syrup; fluoropolyether, fluoroalkyl ether silicone, etc. Etc., and one of these can be used alone or in combination of two or more. The content of the oily component is preferably about 0 to 40% by mass.

Examples of the pH adjuster include lactic acid, citric acid, sodium citrate, glycolic acid, succinic acid, tartrate acid, malic acid, potassium carbonate, sodium hydrogen carbonate, ammonium hydrogen carbonate, sodium hydroxide, potassium hydroxide and triethanolamine. , Monoethanolamine, hydroxyethanediphosphonic acid and the like, and one of these can be used alone or in combination of two or more. The content of the pH adjuster is preferably about 0 to 1% by mass.

Examples of preservatives include benzoic acid, salicylic acid, phenolic acid, sorbic acid, methylparaben, propylparaben, parachlormethacresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichlorocarbanilide, photosensitizer, phenoxyethanol and the like. One of these can be used alone or in combination of two or more. The content of the preservative is preferably about 0 to 5% by mass.

Examples of the emulsifier include anionic surfactants, cationic surfactants, amphoteric surfactants and nonionic surfactants, and more specifically, sorbitan stearate, polyglyceryl-10 diisostearate, and tri. Polyoxyethylene hydrogenated castor oil isostearate, polyoxyethylene cetyl ether, self-emulsifying glyceryl monostearate, decaglyceryl monomyristate, polyoxyethylene sorbit tetraoleate, hydrogenated soybean phospholipid, sodium stearoyl glutamate, monostearic acid Examples thereof include polyethylene glycol, and one of these can be used alone or in combination of two or more. The content of the emulsifier is preferably about 0 to 5% by mass.

Examples of the solubilizer include polyoxyethylene hydrogenated castor oil, polyoxyethylene phytosterol, polyoxyethylene cholesterol, and the like, and one of these can be used alone or in combination of two or more. The content of the solubilizer is preferably about 0 to 5% by mass.

Examples of the chelating agent include alanine, sodium edetate, sodium polyphosphate, sodium metaphosphate, phosphoric acid and the like, and one of these can be used alone or in combination of two or more. The content of the chelating agent is preferably about 0 to 1% by mass.

Examples of the antioxidant include vitamin E, pt-butylphenol, butylhydroxyanisole, dibutylhydroxytoluene, phytic acid, sorbic acid, sodium sulfite, erythorbic acid, L-cysteine hydrochloride and the like. The seeds can be used alone or in combination of two or more. The content of the antioxidant is preferably about 0 to 1% by mass.

Examples of the viscosity modifier include gum arabic, sodium alginate, casein, carrageenan, galactan, carboxyvinyl polymer, carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxymethyl starch, agar, xanthan gum, quince seed, guar gum, collagen, gelatin, cellulose, and the like. Examples thereof include dextrin, dextrin, tragacant gum, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium pectin hyaluronate, pullulan, methyl cellulose, methyl hydroxypropyl cellulose and the like, and one of these can be used alone or in combination of two or more. The content of the viscosity modifier is preferably about 0 to 1% by mass.

Examples of the refreshing agent include lower alcohols such as ethanol, L-menthol, camphor, mentoxypropyldiol, and the like, and one of these can be used alone or in combination of two or more. The content of the refreshing agent is preferably about 0 to 10% by mass.

The cosmetic composition may contain ingredients for skin beautification other than useful ingredients. Examples of skin-beautifying ingredients include placenta extract, glutathione, yukinoshita extract, oil-soluble licorice extract, retinoid, ascorbic acid, ascorbic acid derivative, koji acid, vitamin E, tranexamic acid, cysteine, chamomile extract, linoleic acid, and ellag. Whitening agents such as acids, lucinol, α-hydroxy acids; cell activators such as royal jelly, photosensitizers, cholesterol derivatives, calf blood extracts; rough skin improvers; nonylate valenylamide, nicotinic acid benzyl ester, nicotinic acid β- Butoxyethyl ester, capsaicin, gingeron, cantalis tincture, ictamol, caffeine, tannic acid, α-borneol, tocopherol nicotinate, inositol hexanicotinate, cyclanderate, cinnaridine, trazoline, acetylcholine, verapamiru, cepharanthin, γ-orizanol Blood circulation promoters such as; skin astringents such as zinc oxide and tannic acid; antilipolytic agents such as sulfur and thiantolol, and the like, and one of these can be used alone or in combination of two or more.

Another specific aspect of the composition of one aspect of the present invention is a quasi-drug composition. Quasi-drugs are not particularly limited as long as they are generally known, but for example, they have a mild effect on the human body, are not medical devices, and are designated by the Minister of Health, Labor and Welfare. Specific examples include hair growth agents, hair dyes, and vitamins.

The composition for quasi-drugs may contain, in addition to the first component and the second component, other components commonly used in quasi-drugs, as long as the problems of the present invention can be solved. Other ingredients include, for example, for processing ordinary quasi-drugs such as excipients, binders, disintegrants, stabilizers, fluidizers, surfactants, colorants, sweeteners and lubricants. Additives used and the like can be mentioned. The amount of the additive used is not particularly limited as long as it does not interfere with the solution of the problem of the present invention, and can be set as appropriate.

Another specific embodiment of the composition of one aspect of the present invention is a composition for medicinal cosmetics. Medicinal cosmetics refer to so-called medicated cosmetics that belong to quasi-drugs. The mode of use of the composition for medicinal cosmetics, the type and content of other components, and the like can be appropriately set by those skilled in the art as in the case of the composition for cosmetics and the composition for quasi-drugs.

The composition of one aspect of the present invention is not particularly limited in terms of the production method thereof, and can be produced by a method generally known to those skilled in the art depending on the usage mode of the composition of one aspect of the present invention.

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

[1. Preparation of ASG solution and Arb solution]
Commercially available L-ascorbic acid 2-glucoside and arbutin were dissolved in purified water and serially diluted to prepare ASG solutions and Arb solutions of various concentrations. Further, an ASG + Arb solution was prepared by dissolving Arb in the obtained ASG solution. The ASG solution, Arb solution and ASG + Arb solution were each filtered and sterilized using a membrane filter.

[2. Culture of B16-F10 mouse melanoma cells]
B16-F10 mouse melanoma cells were cultured according to the test methods described in the following two documents. The outline of the test procedure is shown below.
(1) Iwate University Faculty of Education Annual Research Report Vol. 40, No. 1 (1980.10) 93-102
(2) Journal of Applied Pharmaceutical Science Vol. 4 (01), pp. 166-169

Using fetal bovine serum (FBS; Life technologies), α-melanocyte stimulating hormone (α-MSH; Peptide Institute) and Antibiotic-Antimycotic (Life technologies) containing Dalbecco modified Eagle's medium (DMEM; Life technologies) B16-F10 mouse melanoma cells were suspended and seeded on a 6-well culture plate at 1.0 × 10 ⁵ cells / well. Then, a 6-well culture plate was cultured for 24 hours under the conditions of 37 ° C. and a CO ₂ concentration of 5%.

0.02 mL of ASG solution, Arb solution or ASG + Arb solution and fetal bovine serum were added to each well from which the culture supernatant was removed after culturing so that the ASG concentration and / or Arb concentration shown in Tables 1 and 2 described later was obtained. , Α-Melanosite stimulating hormone and Dalvecco modified eagle medium containing 1.98 mL of Antibiotic-Antimycotic were added, and 2 mL of a test solution prepared by mixing was added, and the cells were further cultured for 48 hours. Each well after culturing was subjected to MTT assay and melanin analysis described later.

[3. MTT assay (measurement of cell viability)]
The MTT assay (measurement of cell viability) was carried out according to the test method described in the literature of (2). The changes from the above document are shown below.
The concentration of the 3- (4,5-dimethyl-2-thiazonyl) -2,5-diphenyl-2-H-tetrazolium bromide (MTT; Dojin Kagaku Co., Ltd.) solution was 2.5 mg / ml instead of 2 mg / ml. The culture time after adding the MTT solution was 2 hours instead of 3 hours. Formazan extraction was carried out by adding 2 mL of 0.04 mol / l isopropanol hydrochloride instead of dimethyl sulfoxide (Dimethyl sulfoxide).

[4. Melanin analysis]
The intracellular eumelanin content was measured according to the analytical method described in the literature of Ito et al. Shown in (3) below. The intracellular pheomelanin content was measured according to the analytical method described in the literature of Ito et al. Shown in (4) below. The changes in the pheomelanin analysis from the document (4) are shown below.
(3) Method for analyzing eumelanin: Pigment Cell Melanoma Research (PCMR), 2011, Vol 24, pp. 605-613
(4) Analysis method of pheomelanin: PCMR, 2002, Vol 15, pp. Pages 225-232

For pheomelanin analysis, the conditions for H ₃ PO ₂ to be added to the sample obtained by homogenization were a concentration of 50% (w / v) and an addition amount of 20 μL.

[5. analysis method]
Based on the quantitative values of the eumelanin marker (PTCA) and the pheomelanin marker (4-AHP) obtained in the melanin analysis of 4 above, the amount of eumelanin and the amount of pheomelanin are determined by the following formulas (I) and (II). Calculated.
(I) Amount of eumelanin = amount of PTCA x 25 (coefficient calculated back from 4% yield of PTCA obtained from eumelanin)
(II) Amount of pheomelanin = amount of 4-AHP x 7 (coefficient calculated back from 15% yield of 4-AHP obtained from pheomelanin)

For the coefficients of the formulas (I) and (II), refer to Documents PCMR, 2013, Vol 26, Pages 616-633.

The calculated eumelanin amount and pheomelanin amount were divided by the absorbance as a result of the MTT assay obtained in 3 above to calculate the eumelanin amount and the pheomelanin amount per cell. In addition, the eumelanin ratio and the pheomelanin ratio were calculated when the total amount of the eumelanin amount and the pheomelanin amount was 100%.

[6. Result (1)]
The results of evaluation by the analysis method of 5 above using the test solutions of Examples 1 to 3 and the control are summarized in FIGS. 1 and 2. As shown in these figures, the amount of pheomelanin and the ratio of pheomelanin decreased as the content of ASG increased. Moreover, by using ASG and Arb in combination, the amount of pheomelanin and the ratio of pheomelanin were further reduced. The survival rate of the cultured cells was not significantly different between the test solutions.

[7. Result (2)]
3 and 4 show the results of evaluation by the analysis method of 5 above using the test solutions of Examples 2, Examples 4 to 6 and the control. Similar to FIGS. 1 and 2, the amount of pheomelanin and the ratio of pheomelanin decreased as the content of ASG increased, and the amount of pheomelanin and the ratio of pheomelanin further decreased by using ASG and Arb in combination. On the other hand, as the content of Arb increased, the total amount of melanin decreased. However, the ratio of pheomelanin to total melanin did not decrease. The survival rate of the cultured cells was not significantly different between the test solutions.

Considering that Arb alone did not reduce the ratio of pheomelanin in total melanin, it was found that the effect of reducing the pheomelanin ratio by the combination of ASG and Arb can be said to be a synergistic effect rather than an additive effect. .. In addition, in the test solutions of Examples 1 to 6, no significant difference was observed in the viability of the cultured cells between the test solutions and the controls.

Hereinafter, formulation examples of various aspects of the present invention will be given, but the technical scope of the present invention is not limited to these formulation examples.

(Prescription Examples 1 to 6) Toner

(Prescription Examples 7 to 10) Emulsion

(Prescription Examples 11-16) Essence

(Prescription examples 17-18) Cream

Since the composition according to one aspect of the present invention can not only reduce the amount of pheomelanin but also reduce the ratio of the amount of pheomelanin to the total amount of melanin, it is cytotoxic based on pheomelanin. Expected to have cell protection effect, anti-aging effect (anti-aging), anti-oxidation effect, radical scavenging effect, skin quality maintenance effect, skin quality improvement effect, whitening effect, skin color improvement effect, etc. while reducing adverse effects on the human body. It can contribute to the health of the user.

Claims (7)

A pheomelanin-suppressing composition containing a first component selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof .
Used to reduce the amount of pheomelanin and to reduce the ratio of the amount of pheomelanin to the total amount of melanin consisting of the amount of pheomelanin and the amount of eumelanin.
The composition (excluding the whitening composition) . A first component selected from the group consisting of ascorbic acid, ascorbic acid derivatives and salts thereof, and
A composition for suppressing pheomelanin, which comprises a second component selected from the group consisting of hydroquinone, hydroquinone derivatives and salts thereof .
Used to reduce the amount of pheomelanin and to reduce the ratio of the amount of pheomelanin to the total amount of melanin consisting of the amount of pheomelanin and the amount of eumelanin.
The composition (excluding the whitening composition) . The composition according to claim 2, wherein the second component is a condensate of a substituted or unsubstituted hydroquinone and a sugar. The composition according to any one of claims 2 to 3 , wherein the second component is arbutin. The pheomelanin-suppressing composition contains the first component and the second component so that the mass ratio (first component: second component) is 1: 0.005-2. The composition according to any one of claims 2 to 4 . The first component is a component selected from the group consisting of ascorbic acid, sodium ascorbic acid, ascorbic acid glucoside, ascorbic acid phosphate ester, ascorbic acid sulfate ester, ascorbic acid fatty acid ester, and ascorbic acid alkyl ether. The composition according to any one of 1 to 5. A composition for use in cosmetics or quasi-drugs, which contains the composition according to any one of claims 1 to 6 .
Used to reduce the amount of pheomelanin and to reduce the ratio of the amount of pheomelanin to the total amount of melanin consisting of the amount of pheomelanin and the amount of eumelanin.
The composition (excluding the whitening composition) .