Melanin production inhibitor

Abstract

To provide a melanin production inhibitor, and also provide an external preparation and oral composition both comprising the melanin production inhibitor as a whitening active ingredient.SOLUTION: Provided is a melanin production inhibitor comprising, as an active ingredient, one or two or more selected from triacetin, phenethyl acetate, and cis-3-hexanol. Also provided are an external preparation and oral composition both comprising the melanin production inhibitor as a whitening active ingredient.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a melanin production inhibitor, and to an external skin preparation and an oral composition which contain the melanin production inhibitor as an active ingredient for whitening. [Background technology]

[0002] Skin problems such as wrinkles, sagging, pigmentation, changes in skin tone, loss of skin elasticity, and irregular skin surface morphology Factors that can worsen symptoms include wrinkles and sagging skin, which are caused by dryness and aging, and dermal fibroblasts. The resulting decrease and degeneration of the dermal matrix, including collagen and elastin, Furthermore, oxidative damage caused by external stress such as ultraviolet rays is also an important factor. Pigmentation and changes in skin tone, including darkening of the skin, are still unclear, but are thought to be caused by hormonal abnormalities and exposure to sunlight. The cause is the production of melanin pigment due to the stimulation of ultraviolet rays. It is believed that the cause is abnormal deposition of melanin pigment.

[0003] In order to solve such problems, various methods have been considered. Examples of cell activators include antioxidants such as Passiflora genus essences from the Passifloraceae family (see Patent Document 1). Examples of the melanin-producing inhibitor include extracts of Eucommia ulmoides (see Patent Document 2). As an example of such an effective treatment, an extract from a plant of the genus Cymbidium (see Patent Document 3) is known. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2002-131945 A [Patent Document 2] Japanese Patent Application Publication No. 10-17436 [Patent Document 3] Japanese Patent Application Laid-Open No. 2002-33336 SUMMARY OF THE INVENTION PROBLEM TO BE SOLVED BY THE INVENTION

[0005] An object of the present invention is to provide a melanogenesis inhibitor, a topical skin preparation containing such a melanogenesis inhibitor as a whitening active ingredient, and an oral composition. MEANS FOR SOLVING THE PROBLEM

[0006] The present invention provides (1) A melanogenesis inhibitor containing as an active ingredient one or more selected from triacetin, phenethyl acetate, and cis-3-hexenol. Se (2) A topical skin preparation containing the melanogenesis inhibitor according to (1) as a whitening active ingredient. (3) An oral composition containing the melanogenesis inhibitor according to (1) as a whitening active ingredient. (4) A method for inhibiting melanogenesis, which comprises administering to a subject in need thereof an effective amount of the melanogenesis inhibitor according to (1). to provide. EFFECTS OF THE INVENTION

[0007] The present invention can provide a melanogenesis inhibitor, a topical skin preparation containing such a melanogenesis inhibitor as a whitening active ingredient, and an oral composition. MODE FOR CARRYING OUT THE INVENTION

[0008] Hereinafter, embodiments for carrying out the present invention will be described.

[0009] The melanogenesis inhibitor of the present invention contains as an active ingredient one or more selected from triacetin, phenethyl acetate, and cis-3-hexenol. Se If the above components are those usually used in cosmetics and oral compositions, their raw materials, production methods, purification methods, etc. are not particularly limited.

[0010]

[0011] ​ The above melanin production inhibitor can also be incorporated into external skin preparations and oral compositions as a whitening active ingredient. When incorporated into external skin preparations and oral compositions, the amount of the melanin production inhibitor incorporated is not particularly limited as long as it exhibits a whitening effect, but it is preferably 0.00000001 to 0.5% by mass. If the amount exceeds 0.5% by mass, it may impart an unfavorable aroma to the external skin preparation and oral composition.

[0012] When the melanin production inhibitor of the present invention is incorporated into an external skin preparation, in addition to the above melanin production inhibitor, optional components commonly used in ordinary cosmetics and quasi-drugs can be incorporated to such an extent that the effects of the present invention are not inhibited. Specifically, examples include ultraviolet absorbers, ultraviolet scattering agents, oils, surfactants, thickeners, preservatives, fragrances, pigments, humectants, antioxidants, anti-inflammatory agents, antibacterial agents, anti-aging agents, cell activators, slimming agents, and the like.

[0013] When the melanin production inhibitor of the present invention is incorporated into an external skin preparation, the dosage form is not particularly limited, and any dosage form such as aqueous, oily, or emulsion type may be used.

[0014] When the melanin production inhibitor of the present invention is incorporated into an oral composition, in addition to the above melanin production inhibitor, optional components commonly used in oral compositions can be incorporated to such an extent that the effects of the present invention are not inhibited. Specifically, examples include excipients, binders, bulking agents, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, coating agents, preservatives, flavoring agents, fragrances, coloring agents, plasticizers, and the like. Also, in a range that does not impair the effects of the present invention, combined use with other humectants, cell activators, antioxidants, slimming agents, anti-aging agents, and anti-inflammatory agents is also possible.

[0015] In the external skin preparation and oral composition of the present invention, other whitening active ingredients can also be used in combination.

[0016] The external skin preparation and oral composition of the present invention can be prepared by conventional methods.

Examples

[0017] Hereinafter, the present invention will be specifically described by way of examples, but the scope of the present invention is not limited thereby. In the following examples, the blending amounts are expressed in mass% unless otherwise specified.

[0018] [Melanin production inhibitory effect] B16 mouse melanoma cells (B16F0 cells) were seeded in a 90 mm dish at 18,000 cells per dish. As the seeding medium, DMEM medium supplemented with 10% by mass of fetal bovine serum (FBS) was used. After 24 hours, the medium was replaced with 10% FBS-supplemented DMEM medium in which each component was added to the concentrations (V / V%) shown in Tables 1 to 3, and the cells were further cultured for 6 days. After the culture was completed, the cells were detached by trypsin treatment, collected once in a 15 mL Falcon tube, centrifuged, and the cell precipitate was transferred to a 1.5 mL microtube and centrifuged to obtain a cell precipitate. As a negative control, 1% ethanol was added to 10% FBS-supplemented DMEM, and as a positive control, 1% ethanol was added to 10% FBS-supplemented DMEM containing 50 mM sodium lactate. A tissue lysing agent (trade name Solvable) was added to the obtained precipitate, boiled, returned to room temperature, and the absorbance at 500 nm was measured with a spectrophotometer (Hitachi spectrophotometer U-3010) to determine the total melanin amount. The results are shown in Tables 1 to 3 as relative values with the melanin production amount in the negative control set to 100.

[0019]

Table 1

[0020]

Table 2

[0021]

Table 3

[0022] As shown in Tables 1 to 3, the melanin production inhibitor of the present invention exhibits the effect of suppressing melanin production.

[0023] [Example 12] Cream (1) Squalane 10.0 (mass%) (2) Stearic acid 2.0 (3) Hydrogenated palm kernel oil 0.5 (4) Hydrogenated soy lecithin 0.1 (5) Cetyl alcohol 3.6 (6) Hydrophobic glycerol monostearate 2.0 (7) Glycerol 10.0 (8) Methyl paraben 0.1 (9) Arginine (20 mass% aqueous solution) 15.0 (10) Arbutin 3.0 (11) L - Ascorbic acid 2 - glucoside 2.5 (12) Purified water in an amount such that the total amount is 100 (13) Carboxyvinyl polymer (1 mass% aqueous solution) 15.0 (14) Triacetin 0.01 (15) Perfume 0.1 Production method: The oil - phase components (1) to (6) are heated and dissolved at 80°C. On the other hand, the water - phase components (7) to (12) are heated and dissolved at 80°C. The oil - phase components are added thereto while stirring, and emulsified uniformly by a homogenizer. After the emulsification is completed, (13) is added, cooling is started, and (14) and (15) are added at 40°C and mixed uniformly.

[0024] [Example 13] Emulsion (1) Squalane 10.0 (mass%) (2) Methylphenylpolysiloxane 4.0 (3) Hydrogenated palm kernel oil 0.5 (4) Hydrogenated soy lecithin 0.1 (5) Polyoxyethylene monostearate Sorbitan (20 E.O.) 1.3 (6) Sorbitan monostearate 1.0 (7) Glycerin 4.0 (8) Methyl paraben 0.1 (9) Carbomer 0.15 (10) Arbutin 3.0 (11) L - Ascorbic acid 2 - glucoside 2.5 (12) Purified water in an amount such that the total amount is 100 (13) Arginine (1% by mass aqueous solution) 20.0 (14) Triacetin 0.005 Production method: The oil - phase components (1) to (6) are heated and dissolved at 80°C. On the other hand, the water - phase components (7) to (12) are heated and dissolved at 80°C. The oil - phase components are added while stirring, and emulsified uniformly with a homogenizer. After the emulsification is completed, cooling is started, and (13) and (14) are added sequentially and mixed uniformly.

[0025] [Example 14] Lotion (1) Ethanol 15.0 (mass%) (2) Polyoxyethylene (40 E.O.) hydrogenated castor oil 0.3 (3) Triacetin 0.0001 (4) Phenethyl acetate 0.002 (5) Perfume 0.001 (6) Purified water in an amount such that the total amount is 100 (7) Arbutin 3.0 (8) L - Ascorbic acid 2 - glucoside 2.5 (9) Citric acid 0.02 (10) Sodium citrate 0.1 (11) Glycerin 1.0 (12) Hydroxyethyl cellulose 0.1 Production method: (2) to (5) are dissolved in (1). After dissolution, (6) to (11) are added sequentially, then stirred well, and (12) is added and mixed uniformly.

[0026] [Example 15] Beauty liquid (1) Purified water in an amount such that the total amount is 100 (2) Glycerin 10.0 (mass%) (3) Sucrose fatty acid ester 1.3 (4) Carboxyvinyl polymer (1% aqueous solution) 17.5 (5) Sodium alginate (1% aqueous solution) 15.0 (6) Polyglyceryl monolaurate 1.0 (7) Arbutin 3.0 (8) L - Ascorbic acid 2 - glucoside 2.5 (9) Phytosteryl macadamia nut oil fatty acid 3.0 (10) N - Lauroyl - L - glutamic acid Di(phytosteryl - 2 - octyldodecyl) 2.0 (11) Hydrogenated palm oil 2.0 (12) Squalane (derived from olive) 1.0 (13) Behenyl alcohol 0.75 (14) Beeswax 1.0 (15) Jojoba oil 1.0 (16) 1,3 - Butylene glycol 10.0 (17) L - Arginine (10% aqueous solution) 2.0 (18) Roman chamomile extract 0.2 (19) Triacetin 0.0001 (20) Phenethyl acetate 0.0003 (21) cis - 3 - Hexenol 0.000001 (22) Fragrance 0.2 Production method: Mix the aqueous phase components of (1) to (8) and heat - dissolve at 75°C. On the other hand, mix the oil - phase components of (9) to (16) and heat - dissolve at 75°C. Then, add the oil - phase components to the above - mentioned aqueous phase components for preliminary emulsification, and then emulsify uniformly with a homomixer. After the emulsification is completed, start cooling, add (17) at 50°C. Further cool to 40°C, add (18) to (22), and mix uniformly.

[0027] [Example 16] Cleansing agent (1) Squalane 81.0 (mass%) (2) Polyoxyethylene glyceryl isostearate 15.0 (3) Purified water: an amount such that the total amount is 100 (4) Triacetin 0.05 (5) cis-3-Hexenol 0.1 Production method: (1) and (2) are uniformly dissolved. To this, (3) to (5) are sequentially added and uniformly mixed.

[0028] [Example 17] Facial wash foam (1) Stearic acid 16.0 (mass%) (2) Myristic acid 16.0 (3) Lipophilic glycerol monostearate 2.0 (4) Glycerol 20.0 (5) Sodium hydroxide 7.5 (6) Coconut oil fatty acid amide propyl betaine 1.0 (7) Purified water: an amount such that the total amount is 100 (8) cis-3-Hexenol 0.2 Production method: The oil phase components of (1) to (4) are heated and dissolved at 80°C. On the other hand, the aqueous phase components of (5) to (7) are heated and dissolved at 80°C, and uniformly mixed and stirred with the oil phase components. Cooling is started, and (8) is added at 40°C and uniformly mixed.

[0029] [Example 18] Makeup base cream (1) Squalane 10.0 (mass%) (2) Cetyl alcohol 2.0 (3) Glycerol tri-2-ethylhexanoate 2.5 (4) Lipophilic glyceryl monostearate 1.0 (5) Propylene glycol 11.0 (6) Sucrose fatty acid ester 1.3 (7) Arbutin 3.0 (8) L-Ascorbic acid 2-glucoside 2.5 (9) Purified water: an amount such that the total amount is 100 (10) Titanium oxide 1.0 (11) Bengal 0.1 (12) Yellow iron oxide 0.4 (13) Triacetin 0.0001 (14) Perfume 0.1 Production method: Mix the oil phase components of (1) to (4) and heat and dissolve at 75°C. On the other hand, mix the aqueous phase components of (5) to (9), heat and dissolve at 75°C, add the pigments of (11) to (12) thereto, and uniformly disperse with a homomixer. Add the oil phase component to this aqueous phase component and emulsify with a homomixer. After the emulsification is completed, start cooling, add (13) and (14) at 40°C, and mix uniformly.

[0030] [Example 19] Liquid foundation (1) Methylpolysiloxane 2.0 (mass%) (2) Squalane 5.0 (3) Octyldodecyl myristate 5.0 (4) Cetyl alcohol 1.0 (5) Polyoxyethylene (20 E.O.) Sorbitan monostearate 1.3 (6) Sorbitan monostearate 0.7 (7) 1,3-Butylene glycol 8.0 (8) Xanthan gum 0.1 (9) Methyl paraben 0.1 (10) Arbutin 3.0 (11) L-Ascorbic acid 2-glucoside 2.5 (12) Purified water An amount such that the total amount is 100 (13) Titanium oxide 9.0 (14) Talc 7.4 (15) Bengal red 0.5 (16) Yellow iron oxide 1.1 (17) Black iron oxide 0.1 (18) Triacetin 0.0005 (19) Phenethyl acetate 0.003 (20) cis-3-Hexenol 0.0000001 (21) Perfume 0.01 Production method: Mix the oil-phase components (1) to (6) and heat-dissolve them at 75°C. On the other hand, mix the water-phase components (7) to (12), heat-dissolve them at 75°C, add the pigments (13) to (17) thereto, and uniformly disperse them with a homomixer. Add the oil-phase components and perform emulsification. After the emulsification is completed, start cooling, and sequentially add the components (18) to (21) at 40°C and mix uniformly.

[0031] [Example 20] Water-in-oil type emollient cream (1) Liquid paraffin 30.0 (mass%) (2) Microcrystalline wax 2.0 (3) Petrolatum 5.0 (4) Diglycerin oleate 5.0 (5) Sodium chloride 1.3 (6) Potassium chloride 0.1 (7) Propylene glycol 3.0 (8) 1,3-Butylene glycol 5.0 (9) Methyl paraben 0.1 (10) Arbutin 3.0 (11) L-Ascorbic acid 2-glucoside 2.5 (12) Purified water in an amount such that the total amount is 100 (13) Triacetin 0.01 (14) Fragrance 0.2 Production method: Dissolve (5) and (6) in a part of (12) to make it 50°C, and gradually add it to (4) heated to 50°C while stirring. After mixing this, uniformly disperse it in (1) to (3) heated and dissolved at 70°C. To this, add (7) to (11) heated and dissolved in the remaining part of (12) at 70°C while stirring, and emulsify with a homomixer. After the emulsification is completed, start cooling, and add (13) and (14) at 40°C and mix uniformly.

[0032] [Example 21] Pack (1) Purified water in an amount such that the total amount is 100 (2) Polyvinyl alcohol 12.0 (mass%) (3) Ethanol 17.0 (4) Glycerin 5.0 (5) Polyethylene glycol (average molecular weight 1000) 2.0 (6) Arbutin 3.0 (7) L - Ascorbic acid 2 - glucoside 2.5 (8) Triacetin 0.2 (9) Phenethyl acetate 0.001 (10) cis - 3 - Hexenol 0.001 (11) Perfume 0.001 Production method: Mix (2) and (3), heat to 80°C, and then dissolve in (1) heated to 80°C. After uniformly dissolving, add (4) - (7), start cooling while stirring. Cool to 40°C, add (8) - (11), and mix uniformly.

[0033] [Example 22] Sheet - shaped pack (1) 1,3 - Butylene glycol 5.0 (mass%) (2) Glycerin 5.0 (3) Ethanol 3.0 (4) Triacetin 0.00001 (5) Purified water in an amount such that the total amount is 100 (6) Arbutin 3.0 (7) L - Ascorbic acid 2 - glucoside 2.5 (8) Perfume 0.02 Production method: After uniformly mixing (1) - (8), impregnate a non - woven sheet.

[0034] [Example 23] Tablet (1) Corn starch 44.0 (mass%) (2) Crystalline cellulose the remainder to make 100 (3) Carboxymethylcellulose calcium 5.0 (4) Silica anhydride 0.5 (5) Magnesium stearate 0.5 (6) Triacetin 0.001 Production method: Uniformly mix (1) - (6), and compress - mold with a tableting machine to obtain tablets of 200 mg per tablet. to obtain.

[0035] [Example 24] Candy (1) White sugar 60.0 (mass%) (2) The balance is 100 of starch syrup (3) Triacetin 0.01 (4) Appropriate amount of flavoring Production method: After heating and mixing (1) and (2) until homogenized and then cooling, components (3) and (4) are added at 70 °C and mixed until homogenized, and then molded.

[0036] [Example 25] Drink agent (1) Aminoethylsulfonic acid 1000 mg (2) Thiamine nitrate 10 mg (3) Riboflavin sodium phosphate 5 mg (4) Pyridoxine hydrochloride 10 mg (5) Caffeine anhydrous 50 mg (6) Citric acid 250 mg (7) D-Sorbitol solution 8 mg (8) Phenethyl acetate 1000 mg (9) Appropriate amount of flavoring (10) The balance is 100 mL of purified water Production method: (1) to (9) are sequentially added to (10) and homogenized.

Claims

1. A melanin production inhibitor comprising, as an active ingredient, one or more selected from triacetin, phenethyl acetate, and cis-3-hexenol.

2. A topical skin preparation containing, as a skin-whitening active ingredient, the melanin production inhibitor according to Claim 1.

3. An oral composition containing, as a skin-whitening active ingredient, the melanin production inhibitor according to Claim 1.

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