JP6910027B2 - Tyrosinase activity inhibitor, melanin production inhibitor and whitening agent - Google Patents

Description

The present invention relates to a tyrosinase activity inhibitor, a melanin production inhibitor, and a whitening agent containing an indole-2-carboxylic acid compound or a salt thereof.

Melanin present in the skin is one of the factors that determine the skin color, plays a role of protecting from ultraviolet rays, and is an important factor in cosmetology. The production of melanin is said to proceed by the action of tyrosinase, which may cause spots and freckles. Therefore, conventionally, we have focused on tyrosinase, which is an enzyme involved in the production of melanin, and inhibits the activity and action of tyrosinase to reduce the amount of melanin produced in the skin. So-called whitening agents such as ascorbic acid, arbutin, kojic acid, and glutathione have been used to prevent the resulting phenomena such as spots and freckles.
Recently, it has been reported that chroman-2-one derivatives, serotonin compounds, compounds having an indole skeleton and the like are used in cosmetics.

を含有する化粧品用組成物を、毛髪及び／又は頭皮及び／又は皮膚に適用し、該組成物を毛髪及び／又は頭皮及び／又は皮膚に接触したまま放置し、必要に応じて洗い流すことからなる、ざ瘡、男性型多毛症、脂漏症及びアンドロゲン性脱毛症から選択される、タイプＩ５α−レダクターゼの過剰活性に関連した疾患を有する人のための、毛髪及び／又は頭皮及び／又は皮膚の治療方法を除く美容処理方法が記載されている。
一般式（Ｉ）の化合物にはインドール−２−カルボン酸も包含されうるが、当該特許文献には、具体的に記載が無いのみならず、美白剤としての使用とはまったく異なる目的の美容処理が記載されている。 Among these, patent documents describing the use of compounds having an indole skeleton in cosmetics include the following.
(Patent Document 1)
General formula (I):

The cosmetic composition containing the above is applied to the hair and / or the scalp and / or the skin, and the composition is left in contact with the hair and / or the scalp and / or the skin and washed away as necessary. Of hair and / or scalp and / or skin for persons with diseases associated with overactivity of type I5α-reductase, selected from, acne, male hyperplasia, seborrhea and androgenic alopecia. Beauty treatment methods excluding treatment methods are described.
The compound of the general formula (I) may also include indole-2-carboxylic acid, but the patent document does not specifically describe it, and it is a cosmetological treatment for a purpose completely different from that of use as a whitening agent. Is described.

(Patent Document 2)
It is described that indole-3-carboxylate is used as an antioxidant, cosmetics and food and drink.
Although the patent document describes that it is possible to develop a cosmetic product having high stability without causing discoloration of the preparation as an effect, there is no description about the effect as a whitening agent.
Indole-3-carboxylate has a substituent at the 3-position that is susceptible to electrophilic attack, and since the substituent is a carboxylic acid that is not oxidized, it is significant in terms of stability and is new. Since it is described as an antioxidant compound (paragraph 0015), it cannot be predicted that indole-2-carboxylic acid is similarly effective in the patent document.

上記一般式（Ｉ）及び（ＩＩ）には、インドール−２−カルボン酸及びその誘導体は包含されない。 (Patent Document 3)
A tyrosinase inhibitor is described, which comprises a compound having a 6- or 7-hydroxyindole skeleton represented by the following general formula (I) or (II) as an active ingredient.

The general formulas (I) and (II) do not include indole-2-carboxylic acid and its derivatives.

アルドキシム誘導体が記載され、これに包含されるインドール−５−アルドキシム、インドール−６−アルドキシムが、美白剤として使用されることが記載されている。
しかしながら、上記一般式（１Ａ）には、インドール−２−カルボン酸及びその誘導体は包含されない。 (Patent Document 4)
Equation (1A)

Aldoxime derivatives are described, and indole-5-aldoxime and indole-6-aldoxime included therein are described as being used as whitening agents.
However, the above general formula (1A) does not include indole-2-carboxylic acid and its derivatives.

Special Table 2000-508352 Gazette Japanese Unexamined Patent Publication No. 2014-198790 Japanese Unexamined Patent Publication No. 2011-68632 Japanese Unexamined Patent Publication No. 2008-81459

With conventional whitening agents, the whitening effect may not be sufficient, or the desired medicinal effect may not be obtained due to deterioration in the formulation, etc., and improvement thereof is desired. An object of the present invention is to find a novel tyrosinase activity inhibitor and / or melanin production inhibitor related to a whitening effect in order to solve the problem, and as a result, provide a new whitening agent.

As a result of diligent studies, the present inventors have found that a specific indole-2-carboxylic acid compound or a salt thereof has a tyrosinase activity inhibitory action and a melanin production inhibitory action, and thus is excellent as a whitening component. Was completed.

（式中、Ｒ_１は水素原子又はフェニル基を示し、Ｒ_２は水素原子又は炭素数１〜４のアルキル基を示す）で表わされるインドール−２−カルボン酸化合物又はその塩の１種又は２種以上を有効成分とする美白剤。
（２）式（１）

（式中、Ｒ_１は水素原子又はフェニル基を示し、Ｒ_２は水素原子又は炭素数１〜４のアルキル基を示す）で表わされるインドール−２−カルボン酸化合物又はその塩の１種又は２種以上を有効成分とするメラニン産生抑制剤。
（３）式（１）

（式中、Ｒ_１は水素原子又はフェニル基を示し、Ｒ_２は水素原子又は炭素数１〜４のアルキル基を示す）で表わされるインドール−２−カルボン酸化合物又はその塩の１種又は２種以上を有効成分とするチロシナーゼ活性阻害剤。 That is, the present invention relates to the following invention.
(1) Equation (1)

(In the formula, R ₁ represents a hydrogen atom or a phenyl group, and R ₂ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms). A whitening agent containing seeds or more as an active ingredient.
(2) Equation (1)

(In the formula, R ₁ represents a hydrogen atom or a phenyl group, and R ₂ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms). A melanin production inhibitor containing seeds or more as an active ingredient.
(3) Equation (1)

(In the formula, R ₁ represents a hydrogen atom or a phenyl group, and R ₂ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms). A tyrosinase activity inhibitor containing seeds or more as an active ingredient.

The indole-2-carboxylic acid compound or a salt thereof used in the present invention can be used as a novel whitening agent because it exerts a tyrosinase activity inhibitory action and / or a melanin production inhibitory action.

In the present invention, tyrosinase is a tyrosine oxidase that exists in epidermal cells such as humans and is involved in melanin production, and melanin is a pigment that causes spots and the like that are synthesized with the involvement of tyrosinase and the like. be.

で表わされる化合物である。 The indole-2-carboxylic acid compound used in the present invention has the formula (1).

It is a compound represented by.

Here, R ₁ is a hydrogen atom or a phenyl group, and R ₂ is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
The alkyl group having 1 to 4 carbon atoms R _2, a methyl group, an ethyl group, n- propyl group, i- propyl, n- butyl, s- butyl, i- butyl group, the t- butyl group Can be mentioned.
Examples of the salt of the indol-2-carboxylic acid compound include salts of alkali metals (potassium, sodium, etc.), salts of alkaline earth metals (calcium, magnesium, etc.), ammonium salts, and pharmaceutically acceptable organic amines (tetra). Salts of methylammonium, triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris (hydroxymethyl) aminomethane, lysine, arginine, N-methyl-D-glucamine, etc.) And so on.
Among the compounds represented by the formula (1), indole-2-carboxylic acid, ethyl indole-2-carboxylate, and 6-phenyl-indole-2-carboxylic acid are preferable.
The indole-2-carboxylic acid compound of the present invention or a salt thereof can be used in one kind or a mixture of two or more kinds.

The indole-2-carboxylic acid compound represented by the formula (1) and a salt thereof are all known compounds. The indole-2-carboxylic acid can be purchased from, for example, Tokyo Chemical Industry Co., Ltd., and the derivative thereof can be purchased commercially, but it can also be synthesized by a conventional method.
The indole-2-carboxylic acid compound represented by the formula (1) of the present invention or a tyrosinase activity inhibitor, a melanin production inhibitor or a whitening agent containing a salt thereof as an active ingredient is an indole-2- The carboxylic acid compound or a salt thereof can be used alone or dissolved in a solvent, but may contain other tyrosinase activity inhibitor, melanin production inhibitor or whitening agent preparation, and is usually used in the preparation. It may contain other components.
Further, the tyrosinase activity inhibitor, melanin production inhibitor or whitening agent containing the indol-2-carboxylic acid compound represented by the formula (1) of the present invention or a salt thereof as an active ingredient is a milky lotion, cream, lotion, pack, etc. It can be added to various forms of cosmetics such as cleaning agents, makeup cosmetics, dispersions, ointments, liquids, aerosols, patches, poultices, and liniment agents, or external preparations for the skin.
The amount of the indole-2-carboxylic acid compound represented by the formula (1) of the present invention and a salt thereof in the cosmetic or external preparation for skin is not particularly limited, but is 0.00001 to 10% by mass, preferably 0.0001. A particularly high effect can be expected in the range of ~ 5% by mass.

When the indol-2-carboxylic acid compound represented by the formula (1) in the present invention and a salt thereof are used as an external preparation for whitening skin and a cosmetic for whitening, they are generally used as long as the effects of the present invention are not impaired. Water (purified water, hot spring water, deep water, etc.), alcohols, oils, surfactants, metal salts, gelling agents, powders, water-soluble, used in the preparation of external preparations for skin or cosmetics and external medicines. Polymers, film-forming agents, resins, UV protective agents, inclusion compounds, antibacterial agents, fragrances, deodorants, salts, pH adjusters, refreshing agents, animal / microorganism-derived extracts, plant extracts, blood circulation promoters, It can contain components such as astringents, antilipids, anti-inflammatory agents, cell activators, moisturizers, chelating agents, keratolytic agents, enzymes, hormones, vitamins and the like.

Examples of alcohols include lower alcohols such as ethanol, glycerin, diglycerin, ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, and 1,2-hexanediol. , Polyhydric alcohols such as polyethylene glycol and polypropylene glycol.

The oil agent may be a natural oil, a synthetic oil, or a solid, semi-solid, or liquid, regardless of its properties, for example, hydrocarbons such as squalane, liquid paraffin, and vaseline; adipine. Di-2-heptyl unedecyl acid, isononyl isononanoate, isotolideyl isononanoate, isodesyl isononanoate, cetyl isooctanoate, isostearyl isostearate, cetyl octanate, oleyl oleate, ethyl oleate, decyl oleate, propylene glycol diisononanoate , Di-2-ethylhexanoate neopentylene glycol, propylene glycol dicaprylate, ethylene glycol diisononanoate, neopentyl glycol dicaprate, isostearyl myristate, isopropyl myristate, isosetyl myristate, octyldodecyl myristate, isopropyl palmitate , Isostearyl palmitate, 2-hexyldecyl palmitate, octyl palmitate, myristyl lactate, cetyl lactate, octyl lactate, diisostearyl malate, cholesteryl 12-hydroxystearyl, pentanerislit tetraoctanoate, polyglyceryl tetraisostearate , Tetra2-ethylhexanoate pentaerythlit, ethyl stearate, butyl stearate, ethyl linoleate, isopropyl linoleate, N-lauroyl-L-glutamate-2-octyldodecyl ester, isopropyl isostearate, neopentyl glycol dicaprate , Tri (caprylic capric acid) glyceryl, tri2-ethylhexanoate glyceryl, trimethylolpropane trioctanoate, glyceryl trioctanoate, (2-hexyldecanoic acid / sebacic acid) diglyceryl oligoester, polypropylene glycol oligoester succinate, tri Ester oils such as polyglyceryl isostearate and polyglyceryl diisostearate; waxes such as beeswax, carnauba wax and candelilla wax; fatty acids such as laurate, myristic acid, palmitic acid, stearic acid, linoleic acid, linoleic acid and oleic acid; Higher alcohols such as stearic acid and behenyl alcohol; Silicone oils such as dimethylpolysiloxane and methylphenylpolysiloxane; Fluorine oils such as perfluoropolyether; Olive oil, castor oil, jojoba oil, macadamian nut oil, apricot oil , Persic oil, Examples thereof include safflower oil, sunflower oil, avocado oil, meduhome oil, camellia oil, almond oil, sesame oil, sesame oil, borage oil, shea butter and other oils and fats derived from plants and animals.

Surfactants are used for emulsification and solubilization of oils and the like, and anionic, cationic, nonionic and amphoteric activators can be used.

The metal soap is a salt of a fatty acid or the like and a metal, and examples thereof include aluminum stearate, magnesium stearate, and zinc laurate.

Gelling agents are used to stabilize the system, improve usability, and improve usability, and include amino acid derivatives such as N-lauroyl-L-glutamic acid, dextrin fatty acid esters such as dextrin palmitic acid ester, and sucrose fatty acid esters. Examples include organically modified clay minerals.

The powder is mainly used for various purposes such as coloring in makeup cosmetics, concealing the skin, or improving the feeling of use, and if it is used for ordinary cosmetics, its shape (spherical, needle-shaped, plate). Any of these can be used regardless of the shape (shape, etc.), particle size (foam-like, fine particles, pigment grade, etc.), and particle structure (porous, non-porous, etc.). For example, examples of the inorganic powder include barium sulfate, calcium carbonate, talc, mica, synthetic mica, mica, kaolin, sericite, silicic acid, silicic anhydride, aluminum magnesium silicate, ceramic powder, boron nitride and the like. Examples of the organic powder include polyester powder, polyethylene powder, polystyrene powder, nylon powder, lauroyl lysine and the like, and examples of colored pigments include iron oxide, carbon black, chromium oxide, dark blue, ultramarine and other inorganic pigments, and tar-based pigments. Examples include raked pigments and raked natural pigments. Pearl pigments include titanium oxide-coated mica, titanium oxide-coated mica, bismuth oxychloride, titanium oxide-coated bismuth oxychloride, titanium oxide-coated talc, and fish scales. Examples include foils, titanium oxide-coated colored mica, and other natural pigments such as tar pigments and carmic acid. These powders may be composited or surface-treated with an oil agent, silicone, or a fluorine compound.

Examples of UV protection agents include -2-ethylhexyl paramethoxysilicate, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sodium sulfate, and 4-t-butyl-4'-methoxydi. Benzoylmethane, 2-phenyl-benzimidazol-5-sulfate, isopropyl methoxycinnamate, isoamyl methoxycinnamate, 2-ethoxyethyl 3- (4-methoxyphenyl) propenate, diisopropyl methylsilicate, glyceryl-ethylhexa Noato-dimethoxycinnamate, titanium oxide, zinc oxide and the like can be mentioned.

The water-soluble polymer is used to stabilize the system, improve usability and usability, and is also used to obtain a moisturizing effect. Specific examples of water-soluble polymers include plant-based polymers such as carrageenan, pectin, agar, and locust bean gum; microbial-based polymers such as xanthan gum; animal-based polymers such as casein and gelatin; starch-based polymers such as starch. Cellulosic polymers such as methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose and crystalline cellulose; alginic acid polymers such as sodium alginate; vinyl polymers such as carboxyvinyl polymer and the like.

Examples of the antibacterial agent include benzoic acid, sodium benzoate, paraoxybenzoic acid ester, benzalkonium chloride, phenoxyethanol, isopropylmethylphenol and the like.

Anti-inflammatory agents are used for the purpose of suppressing inflammation such as hot spots and erythema of the skin after sunburn, and are used for the purpose of suppressing inflammation such as hot spots and erythema of the skin after sunburn. Extract, Arnica extract, Inchinko extract, Irakusa extract, Oubaku extract, Otogirisou extract, Chamomile extract, Kinginka extract, Cresson extract, Comfrey extract, Salvia extract, Sikon extract, Perilla extract Examples include erythema extract, gentian extract and the like.

The cell activator is used for the purpose of improving rough skin, caffeine, royal jelly, silk protein and its decomposition products or derivatives thereof, lactoferrin or its decomposition products, mucopolysaccharides such as chondroitin sulfate and hyaluronic acid, or theirs. Salt, collagen, yeast extract, lactic acid bacterium extract, bifidus bacterium extract, fermented metabolism extract, ginkgo extract, barley extract, assembly extract, taiso extract, carrot extract, rosemary extract, glycolic acid, Examples thereof include organic acids such as citric acid, lactic acid, malic acid, tartaric acid and succinic acid and derivatives thereof.

The active oxygen remover is used for the purpose of suppressing the production of lipid peroxide, and is used for superoxide dismutase, mannitol, quercetin, catechin and its derivatives, rutin and its derivatives, buttonpi extract, yashajitsu extract, melissa extract, and Rakan fruit extract. Vitamin A such as retinol and its derivatives, vitamin A such as carotinoid, thiamine and its derivative, riboflavin and its derivative, pyridoxin and its derivative, vitamin B such as nicotinic acid and its derivative, vitamin E such as tocopherol and its derivative, Examples thereof include dibutylhydroxytoluene and butylhydroxyanisole.

Moisturizers include proteins such as elastin and keratin or derivatives thereof, hydrolysates and amino acids such as salts thereof, glycine, serine, aspartic acid, glutamic acid, arginine and theanine and their derivatives, sorbitol, erythritol and trehalose. Inositol, glucose, sucrose and its derivatives, dextrin and its derivatives, sugars such as honey, D-pantenol and its derivatives, urea, phospholipids, ceramides, auren extract, shobu extract, dioe extract, senkyu extract, Examples thereof include Zenia oyster extract, Tachijakousou extract, Dextrin extract, Hamamelis extract, Bodaiju extract, Maronnier extract, Marumero extract and the like.

Examples are shown below, but the technical scope of the present invention is not limited to the examples.
[Example 1]
Tyrosinase activity inhibitory action Indole-2-carboxylic acid and 6-phenyl-indole-2-carboxylic acid are used as the compounds of the present invention, and arbutin and indole-3-carboxylic acid, which are known whitening agents as comparative examples, are used for tyrosinase activity. Was measured.

The experimental method is as follows.
30 μL of a solution of the test compounds of Examples and Comparative Examples dissolved in DMSO so as to have a final concentration of 50 μM in the system was mixed with 770 μL of phosphate buffer. Next, 800 μL of a tyrosinase enzyme (manufactured by SIGMA) solution (25 U / mL) was added, and then 400 μL of a 0.2% DOPA solution was added. The absorbance value at 475 nm was measured by a meter (manufactured by Shimadzu Corporation). From the absorbance value at 475 nm for 10 seconds to 120 seconds, ΔABS 475 nm / min per minute was determined, and the tyrosinase activity ratio when only the solvent was 1 was calculated.

As shown in the above table, when the compound of the present invention was used, the tyrosinase activity was lower than that of the comparative compound indole-3-carboxylate, and thus it was shown that the tyrosinase inhibitory effect was higher than that of indole-3-carboxylate. In addition, the 6-phenyl-indole-2-carboxylic acid of the present invention showed a tyrosinase inhibitory effect almost equivalent to that of the comparative compound arbutin.

[Example 2]
Melanin production inhibitory action The melanin production rate was measured using indole-2-carboxylic acid and ethyl indole-2-carboxylic acid as the compounds of the present invention, and kojic acid, which is a known whitening agent as a comparative example.
The experimental method is as follows.

The test compounds of Examples and Comparative Examples were dissolved in an aqueous ethanol solution and added to a three-dimensional skin model (MEL-300 kit Asian donor MEL-300-A manufactured by Kurabou Co., Ltd.) so as to have a final concentration of 0, 70, 140 mM. Then, the cells were cultured at 37 ° C. for 15 days. It was then washed 3 times with PBS, the skin model was removed from the cup and transferred to a tube. 450 μL of SDS solution (1.0% SDS, 0.05 mM EDTA, 10 mM Tris HCl) was added and homogenized. Next, 5 μL of proteinase K (20 mg / mL) was added and reacted at 45 ° C. overnight. Further, 50 μL of 500 mM sodium carbonate solution and 10 μL of 30% hydrogen peroxide were added, reacted at 80 ° C. for 30 minutes, and ice-cooled. After cooling, 100 μL of chloroform-methanol (2: 1) was added and stirred. Centrifugation was carried out at 10000 × g for 10 minutes, and the absorbance of the supernatant at 405 nm was measured with a microplate reader (μQuant) (BIO-TEK INSTRUMENTS INC).
The above operation was performed using synthetic melanin as a standard in advance, a calibration curve was prepared, the amount of melanin produced was obtained from the absorbance measured using the calibration curve, and the melanin production rate when only the solvent was 1 was calculated.
The experiment was carried out for indole-2-carboxylic acid and ethyl indole-2-carboxylic acid, respectively, using kojic acid as a comparative example.
The test had no effect on the cells of the skin model.

As shown in the above table, all of the compounds of the present invention had a melanin production rate almost equal to that of kojic acid, which is a known whitening agent, at a concentration of 140 mM. Indicated.

The following is a prescription example of a cosmetic or skin external preparation containing the tyrosinase activity inhibitor, melanin production inhibitor or whitening agent of the present invention. The total amount of each example is 100% by mass. These are excellent in stability and can be expected to have the effect of brightening the skin.

[Prescription example 1: Toner]
(Manufacturing method)
A. The following components (5) to (9) are mixed and dissolved.
B. The following components (1) to (4) and (10) are mixed and dissolved.
C. A was added to B and mixed to obtain a lotion.

(Ingredient) (%)
1 Glycerin 5.0
2 1,3-butylene glycol 5.0
3 Lactic acid 0.05
4 Sodium lactate 0.1
5 Polyoxyethylene monooleate (20 mol) sorbitan 1.2
6 Ethanol 8.0
7 Indole-2-carboxylic acid 0.01
8 Methyl paraoxybenzoate 0.1
9 Fragrance 0.05
10 Remaining amount of purified water

[Prescription example 2: Essence]
(Manufacturing method)
A. The following components (1) to (10) are mixed and dissolved.
B. The following components (11) to (17) are mixed and dissolved.
C. B was added to A and mixed to obtain a beauty essence.

(Ingredient) (%)
1 Dipropylene glycol 5.0
2 1,3-butylene glycol 8.0
3 Alkyl acid / alkyl methacrylate copolymer (* 1) 0.16
4 Xanthan gum 0.2
5 Remaining amount of purified water 6 Sodium hydroxide 2% solution 2.0
7 Ethyl indole-2-carboxylate 0.005
8 Sodium hyaluronate 0.01
9 Hydrolyzed elastin 0.01
10 Hydrolyzed collagen 0.1
11 Polyoxyethylene isostearate (50 mol) Hydrogenated castor oil 0.3
12 isostearic acid 0.2
13 Refined jojoba oil 0.2
14 Astaxanthin 0.001
15 Methyl paraoxybenzoate 0.1
16 Ethanol 2.0
17 Fragrance 0.02
(* 1) CARBOPOL 1382 (manufactured by LUBRIZOL)

[Prescription example 3: Oil-in-water emulsion]
(Manufacturing method)
A. Ingredients (1) to (5) are uniformly dissolved and mixed at 70 ° C.
B. The components (6) to (14) are uniformly dissolved and mixed at 80 ° C.
C. B is added to A and emulsified at 70 ° C.
D. After the components (15) to (17) were added to and mixed with C, the mixture was cooled to 40 ° C. to obtain an oil-in-water emulsion.

(Ingredient) (%)
1 1,3-butylene glycol 5.0
2 Dibutylene glycol 5.0
3 Remaining amount of purified water 4 6-Phenyl-indole-2-carboxylic acid 0.001
5 Sodium hydroxide 2% solution 0.2
6 N-myristoylation-L-glutamic acid 0.2
7 Polyoxyethylene (10 mol) hardened castor oil (* 2) 0.2
8 Macadamia nut oil fatty acid phytosteryl 1.0
9 Didimethylpolysiloxane (* 3) 3.0
10 N-stearoyl phytosphingosine 0.1
11 Tocopherol acetate 0.01
12 Stearyl alcohol 0.5
13 1,2-Pentanediol 0.1
14 Carboxyvinyl polymer (* 4) 0.15
15 (Na acrylate / Na acryloyl dimethyl taurine)
Copolymer (* 5) 0.1
16 Ethanol 5.0
17 Fragrance 0.1
(* 2) HCO-10 (manufactured by Nippon Surfactant Industry Co., Ltd.)
(* 3) Silicon KF-96A (6CS) (manufactured by Shin-Etsu Chemical Co., Ltd.)
(* 4) CARBOPOL980 (manufactured by LUBRIZOL ADVANNCED MATERIALS)
(* 5) SIMULGEL EG (manufactured by SEPIC)

Claims (3)

Equation (1)

(In the formula, R ₁ represents a hydrogen atom or a phenyl group, and R ₂ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms). A whitening agent containing seeds or more as an active ingredient. Equation (1)

(In the formula, R ₁ represents a hydrogen atom or a phenyl group, and R ₂ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms). A melanin production inhibitor containing seeds or more as an active ingredient. Equation (1)

(In the formula, R ₁ represents a hydrogen atom or a phenyl group, and R ₂ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms). A tyrosinase activity inhibitor containing seeds or more as an active ingredient.