JP2003252718A - In vivo dihydroxyindole compound polymerization inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a polymerization inhibitor for inhibiting the in vivo dihydroxyindole compound polymerization caused by the irradiation of long wavelength UV light (UVA), and to provide a skin care preparation containing the polymerization inhibitor. <P>SOLUTION: This polymerization inhibitor comprises 3-O-ethylascorbate. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a polymerization inhibitor that suppresses the polymerization of a dihydroxyindole compound in vivo by irradiation with long-wavelength ultraviolet light (UVA) by 3-O-ethylascorbic acid, and a skin external preparation containing the same. is there.

[0002]

BACKGROUND OF THE INVENTION Conventionally, the blackening of the skin by ultraviolet rays is caused by the increase in the activity of the enzyme tyrosinase in the melanocytes existing in the basal layer of the epidermis after the irradiation of ultraviolet rays, and the melanin produced from tyrosine is produced in the melanocytes. It has been described that it is caused by melanin in the surrounding keratinocytes. Therefore, as a method of preventing skin darkening due to ultraviolet rays, in addition to an ultraviolet ray blocking agent that absorbs or scatters ultraviolet rays, kojic acid and arbutin, which are so-called whitening agents that suppress the activity and synthesis of tyrosinase, are used. Has been. Since tyrosinase protein biosynthesis is involved in the above process, it takes at least a few days for the activity of tyrosinase to increase, and it takes 3-5 days for the surrounding keratinocytes to receive melanin and appear dark on the skin. It takes a while.

However, since the skin darkening phenomenon caused by excessive sunlight exposure in leisure or sea bathing occurs within a short time of less than one day, the inventors of the present invention have conventionally considered the enzymatic reaction involving tyrosinase. We suspected that there might be a different mechanism of action from the melanin production by. Therefore, we conducted a study using a solar simulator for the purpose of experimentally reproducing the darkening of the skin that occurred within this one day, and of the ultraviolet rays that we commonly use, we selected 16 of the long-wavelength ultraviolet rays (UVA; 320-400 nm). ~ 45J
It was found that the irradiation of / cm ² resulted in immediate blackening after the end of irradiation and the blackening lasted for one week or longer. This U
As a result of biochemical and histochemical elucidation of the persistent blackening phenomenon caused by VA, dihydroxyindole and its related compounds, which are relatively stable colorless and transparent compounds produced by melanocytes present in the basal layer of the epidermis, were identified. It was found that UVA was directly applied to the melanin monomer to produce melanin. Then, it was found that 3-O-ethylascorbic acid can suppress the production of melanin by directly polymerizing melanin monomers such as dihydroxyindole and its related compounds by UVA.

The present invention has been made on the basis of such findings, and provides a polymerization inhibitor of a dihydroxyindole compound in vivo which can prevent skin darkening due to a new mechanism of action, and a skin external preparation containing the same. The purpose is to provide.

[0005]

Means for Solving the Problems That is, the present invention is a polymerization inhibitor which suppresses the polymerization of a dihydroxyindole compound in a living body caused by irradiation with long wavelength ultraviolet light (UVA), which is 3-O-ethylascorbine. A polymerization inhibitor characterized by comprising an acid, and a skin external preparation containing the same, in particular, an immediate external anti-blackening skin external preparation.

It has not been known at all until now that 3-O-ethylascorbic acid can prevent melanization of the skin by suppressing the melanization caused by the irradiation of the dihydroxyindole compound in vivo with ultraviolet rays. .

The structure of the present invention will be described in detail below. The 3-O-ethylascorbic acid used in the present invention can be synthesized by ethoxylating the hydroxyl group at the 3-position of ascorbic acid, or can be obtained as a commercial product from Nippon Hypox Co., Ltd. (JP-A-8-134055). Issue).

The long wavelength ultraviolet light (UVA) referred to in the present invention is
It is continuous or single-wavelength ultraviolet light of 290 to 400 nm, such as fluorescent lamps, solar simulators, and monochromators. It is preferably ultraviolet light in the UVA region of 320 to 400 nm.

The dihydroxyindole compound referred to in the present invention includes DHICA (5,6-dihydroxyindole-2-carboxylic acid) and salts thereof, DHI (5,6-dihydroxyindole), 6H5MICA (6-hydroxy-5-methoxy). Indole-2-carboxylic acid), 5
H6MICA (5-hydroxy-6-methoxyindole-2-carboxylic acid) and the like can be mentioned. Of these, especially
DHICA (5,6-dihydroxyindole-2-carboxylic acid) and its salts are preferred.

The polymerization inhibitor for the polymerization of the dihydroxyindole compound (black-brown melanization) by ultraviolet rays of the present invention is used as a whitening agent, as well as ultraviolet rays, especially UV rays.
It can be applied to improve or prevent the skin symptoms associated with A, such as immediate blackening.

Further, according to the present invention, there is provided a skin external preparation containing the above-mentioned polymerization inhibitor.

The content of the polymerization inhibitor in the external preparation for skin of the present invention is 0.001 to 50.0% by mass, preferably 0.01 to 10.0% by mass, based on the total amount of the external preparation. 0.
If it is less than 001% by mass, the effect of the present invention is not sufficiently exhibited, and if it exceeds 50.0% by mass, formulation is difficult, which is not preferable. Further, even if it is blended in an amount of 10.0% by mass or more, the effect is not significantly improved.

In addition to the above essential ingredients, the external preparation for skin of the present invention may optionally contain various ingredients and additives commonly used in cosmetics, quasi drugs and pharmaceuticals as shown below. It can be blended appropriately.

That is, glycerin,
Moisturizers such as petrolatum, urea, hyaluronic acid, heparin,
PABA derivative (para-aminobenzoic acid, escarol 5
07, etc.), cinnamic acid derivative (neoheliopan, parsol MCX, sungard B etc.), salicylic acid derivative (octyl salicylate etc.), benzophenone derivative (ASL-
24, ASL-24S etc.), dibenzoylmethane derivatives (parsol A, parsol DAM etc.), heterocyclic derivatives (tinuvin series etc.), UV absorbers / scattering agents such as titanium oxide, disodium edetate, trisodium edetate. , Sequestering agents such as citric acid, sodium citrate, tartaric acid, sodium tartrate, lactic acid, malic acid, sodium polyphosphate, sodium metaphosphate, gluconic acid, sebum inhibitors such as salicylic acid, sulfur, caffeine, tannin, benzal chloride Ruconium, benzethonium chloride, sterilizing agents such as chlorhexidine gluconate, diphenhydramine hydrochloride, tranexamic acid, guaiazulene, azulene,
Allantoin, hinokitiol, glycyrrhizic acid and its salts, glycyrrhizic acid derivatives, anti-inflammatory agents such as glycyrrhetinic acid, vitamin A, vitamin B group (B ₁ , B ₂ , B
₆ , B ₁₂ , B ₁₅ ), folic acid, nicotinic acids, pantothenic acids, biotin, vitamin D group (D ₂ , D ₃ ), vitamin E, ubiquinones, vitamin K (K ₁ , K ₂ , K ₃ , K _4). )
Such as vitamins, aspartic acid, glutamic acid, alanine, lysine, glycine, glutamine, serine, cysteine, cystine, tyrosine, proline, arginine, pyrrolidonecarboxylic acid, taurine, thiotaurine, glutathione, and amino acid derivatives thereof, retinol, tocopherol acetate. , Arbutin, kojic acid, ellagic acid, placenta extract and other whitening agents, butylhydroxytoluene, butylhydroxyanisole, propyl gallate and other antioxidants, zinc chloride, zinc sulfate, zinc carbonate, zinc oxide, aluminum potassium sulfate, etc. Astringent, glucose, fructose, maltose, sucrose, trehalose, erythritol, maltose, xylitol, sugars such as lactitol, licorice, chamomile, horse chestnut, Yukinoshita, peony,
Karin, Oogon, Ooaku, Ouren, Juyaku,
In addition to various plant extracts such as ginkgo biloba, an oily component, a surfactant, a thickener, alcohols, a powder component, a coloring material and the like can be appropriately mixed.

The external preparation for skin of the present invention may be any ointment, cream, milky lotion, lotion, pack, bath agent or the like as long as it is a conventional external preparation for skin, and its form is not particularly limited. Further, the external preparation for skin of the present invention is useful not only as a cosmetic but also as a drug or a quasi drug.

[0016]

The present invention will be described in more detail with reference to Examples. The present invention is not limited to this. The blending amount is% by mass. Prior to the examples, the DHI of 3-O-ethylascorbic acid of the present invention by UV light
The test method and the result concerning the inhibitory effect of CA (5,6-dihydroxyindole-2-carboxylic acid) on the dark brown melanization will be described.

(1) Measurement of the inhibitory effect on the dark brown melanization of DHICA caused by ultraviolet rays containing 3-O-ethylascorbic acid as an active ingredient. On the dark brown melanization of DHICA caused by ultraviolet rays containing 3-O-ethylascorbic acid as an active ingredient. The inhibitory effect was evaluated by the inhibitory effect on the dark brown melanization of DHICA by ultraviolet rays as shown below. Dissolve 0.01 to 1.0 mg / ml of DHICA or its sodium salt in water, and dispense 100 μl into microplate wells. 1 ascorbic acid or its derivative adjusted to each concentration
00 μl was added and long-wavelength ultraviolet light was irradiated for 1 hour using a FL-20BLB fluorescent lamp, the absorbance at 405 nm was measured with a microplate reader, the degree of black-brown melanization was evaluated, and the effect of the compound was evaluated. The results are shown in Table 1.

[0018]

[Table 1] ───────────────────────────────── Test substance Sample concentration DHICA UV melanization (%) Inhibition Rate (%) ───────────────────────────────── 3-O-ethylascorbic acid 0.1 80 3-O- Ethyl ascorbic acid 0.01 40 AA-2G ^{* 1} 0.1 20 Ascorbic acid 0.1 70 ─────────────────────────────────

* 1: Ascorbic acid-2-O-α-glucoside

(4) Actual Use Test of Inhibitory Effect on Skin Blackening by UVA The effect of applying the external preparation according to the present invention to the outer skin is
It was evaluated from the prevention rate and the improvement rate with respect to the degree of blackening of the skin color due to. For the test, arms of 40 healthy male and female panels were used. Two arbitrary sites were provided on the arm and used as test sites. The panel was divided into 4 groups of 10 people each, and an appropriate amount of the sample was applied to one of the sites and the control was applied to the other site of the emulsion having the composition (mass%) shown in Table 2. It was applied three times a day for 21 days. Ultraviolet ray simulator (Sola
A WG 335 nm filter was installed at R Light Company, and UVB was cut. ) Was used for irradiation. The UVA irradiation dose of the equipment used was 20 J / cm ^{2, and} it was 1
Since the average daily UVA amount is 40 to 60 J / cm ² , it corresponds to about half to one-third of the UVA amount bathed in a sunny day in summer. The skin color was measured using Mexameter MX16 before, immediately after, 20 minutes, 3 hours, 1 day, 7 days, 14 days, and 21 days after irradiation. The effectiveness was evaluated by visually comparing the degree of blackening between the two sites at each measurement at 5 levels and the results of device measurement. As a sample, as the product of the present invention, 5% 3-O-
Ethyl ascorbic acid-containing emulsion, 1% 3-O-ethylascorbic acid-containing emulsion, and 1% AA-2 as a comparative product
G (ascorbic acid-2-O-α-glucoside) -containing emulsion, 1% ascorbic acid-containing emulsion was used. The results are shown in Table 2.

[0021]

[Table 2] ────────────────────────────                                  Inventive product Comparative product   Sample ────── ──────                                  One two one two ──────────────────────────── 3-O-ethylascorbic acid 5.0 − − − 3-O-ethylascorbic acid-1.0 --- AA-2G − − 1.0 − Ascorbic acid − − − 1.0 Water − 4.0 4.0 4.0 Glycerin 10.0 10.0 10.0 10.0 1,3-butylene glycol 4.0 4.0 4.0 4.0 Ethanol 7.0 7.0 7.0 7.0 Polyoxyethylene (20 mol)           Oleyl alcohol 0.5 0.5 0.5 0.5 Purified water Residual Residual Residual ──────────────────────────── UVA blackening suppression effect ◎ ◎ ○ ○ ○ ────────────────────────────

As is clear from Table 2, the sample of the present invention containing 3-O-ethylascorbic acid was AA-2.
It exhibited a superior effect of suppressing skin blackening due to UVA as compared with the comparative product containing G or ascorbic acid. next,
The prescription example of the external preparation for skin according to the present invention is shown.

Example 1 Cream (formulation) Stearic acid 5.0% by mass Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 3-O-ethylascorbic acid 01 Caustic potassium 0.2 Sodium bisulfite 0.01 Preservative Suitable amount Perfume Suitable amount Ion-exchanged water Residual (production method) Propylene glycol and 3-O in ion-exchanged water
-Add ethyl ascorbic acid and caustic potash to dissolve, heat and keep at 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). Add the oil phase gradually to the water phase,
After adding all, keep the temperature for a while and let the reaction occur. Then, it is uniformly emulsified with a homomixer and cooled to 30 ° C. with thorough stirring.

Example 2 Cream (formulation) Stearic acid 2.0% by mass Stearyl alcohol 7.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) Cetyl alcohol ether 3.0 Glycerin monostearate 2.0 Propylene glycol 5.0 3-O-ethylascorbic acid 0.05 Sodium hyaluronate 0.1 Sodium bisulfite 0.03 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water residual ( Manufacturing method) Add propylene glycol to ion-exchanged water,
Heat to maintain 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the aqueous phase to carry out preliminary emulsification, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring.

Example 3 Cream (Formulation) Solid paraffin 5.0% by mass Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) sorbitan monolaurate 2 0.0 Soap powder 0.1 Borax 0.2 3-O-ethylascorbic acid 0.05 Acetylated sodium hyaluronate 0.1 Serine 1.0 Thiotaurine 0.1 Sodium bisulfite 0.03 Trisodium edetate 0.1 Ethyl paraben 0.3 Fragrance Suitable amount Ion-exchanged water Residual (manufacturing method) Soap powder and borax are added to ion-exchanged water, dissolved by heating and kept at 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is stirred into the water phase and gradually added to carry out the reaction. After the reaction is completed, the mixture is uniformly emulsified with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

Example 4 Emulsion (formulation) Stearic acid 2.5% by mass Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) Monooleate ester 2.0 Polyethylene glycol 1500 3.0 Triethanolamine 1 .0 Carboxyvinyl polymer 0.05 (trade name: Carbopol 941, BFGoodrich Chemical c
ompany) 3-O-ethylascorbic acid 0.01 4-methoxysalicylic acid potassium 2.0 trimethylglycine 3.0 hypotaurine 0.1 urea 0.1 sodium bisulfite 0.01 ethylparaben 0.3 fragrance ion exchange water residual (Production method) A carboxyvinyl polymer is dissolved in a small amount of ion-exchanged water (phase A). Polyethylene glycol 1500 and triethanolamine were added to the remaining ion-exchanged water, and the mixture was heated and dissolved and maintained at 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the aqueous phase for preliminary emulsification, the phase A is added and the mixture is homogenized with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. while being well stirred.

Example 5 Emulsion (prescription) Microcrystalline wax 1.0% by mass Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Vitamin E acetate 0.1 Isostearate 0.5 Sorbitan sesquiolein Acid ester 4.0 Polyoxyethylene (20 mol) Sorbitan monooleate 1.0 Laurine dimethylaminoacetic acid betaine 0.5 Propylene glycol 7.0 3-O-ethylascorbic acid 10.0 Arbutin 5.0 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Fragrance Suitable amount Ion-exchanged water Residual (production method) Add propylene glycol to ion-exchanged water,
Heat to maintain 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and kept at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added to this and the mixture is uniformly emulsified with a homomixer. After emulsification, cool to 30 ° C while stirring well.

Example 6 Jelly (formulation) 95% ethyl alcohol 10.0 mass% dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 1.0 (trade name: Carbopol) 940, BFGoodrich Chemical company) Caustic soda 0.15 L-arginine 0.1 3-O-ethylascorbic acid 7.0 2-Hydroxy-4-methoxy benzophenone sulfonate sodium 0.05 Ethylenediaminetetraacetate / 3 sodium / dihydrate 0 .05 Methylparaben 0.2 Fragrance Suitable amount Ion-exchanged water Residue (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while 3-O-ethylascorbic acid and polyoxyethylene (50 mol) oleyl are dissolved in 95% ethanol. Alcohol ete It was dissolved, added to the aqueous phase. Then
After adding other components, the mixture is neutralized with caustic soda and L-arginine to increase the viscosity.

Example 7 Beauty essence (formulation) (Phase A) Ethyl alcohol (95%) 10.0% by mass Dibutylhydroxytoluene 0.01 Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl ethyl ether 0 . 1 3-O-ethylascorbic acid 1.5 AA-2G 2.0 Yukinoshita extract 0.1 Ougon extract 0.1 methylparaben 0.15 (phase B) potassium hydroxide 0.1 (phase C) glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 (trade name: Carbopol 940, BFGoodrich Chemical c
ompany) Sodium metaphosphate 0.1 Dye Appropriate amount of purified water Residual (manufacturing method) Phase A and C are uniformly dissolved, and A is added to phase C
Add phase and solubilize. Next, phase B is added and then filling is performed.

Example 8 Pack (formulation) (Phase A) Dipropylene glycol 5.0% by mass Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) 3-O-ethylascorbic acid 0.01 Olive oil 5.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Perfume 0.2 (C phase) Sodium hydrogen sulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, degree of polymerization 2,000) Ethanol 7.0 Purified water Remaining (manufacturing method) A phase, B phase, and C phase are uniformly dissolved,
Phase B is added to the phase to solubilize it. Next, this is added to phase C and then filled.

Example 9 Solid foundation (formulation) Talc 43.1% by mass Kaolin 15.0 Sericite 10.0 Zinc white 7.0 Titanium dioxide 3.8 Yellow iron oxide 2.9 Black iron oxide 0.2 Squalane 8 0.0 isostearic acid 4.0 POE sorbitan monooleate 3.0 isocetyl octanoate 2.0 3-O-ethylascorbic acid 0.5 preservative proper amount perfume appropriate amount (manufacturing method) talc to black iron oxide powder component with a blender Mix well and add to this squalane to isocetyl octoate oil component, 3-O-ethylascorbic acid, preservative,
Add fragrance and knead well, then fill and mold in a container.

Example 10 Emulsion type foundation (cream type) (Formulation) (Powder part) Titanium dioxide 10.3% by mass Sericite 5.4 Kaolin 3.0 Yellow iron oxide 0.8 Bengala 0.3 Black iron oxide 0.2 (Oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (Aqueous phase) Purified water 50.0 1,3-Butylene glycol 3.0 3 -O-Ethyl ascorbic acid 1.0 Tranexamic acid 2.0 Sorbitan sesquioleate ester 3.0 Preservative proper amount Perfume proper amount (Production method) After heating and stirring the aqueous phase, the powder portion thoroughly mixed and pulverized is added and homogenized. Process with a mixer. Further, the heated and mixed oil phase is added, and the mixture is treated with a homomixer. Then, the fragrance is added with stirring and the mixture is cooled to room temperature.

Example 11 Sunscreen Emulsion (W / O Emulsion) (Oil Phase) Volatile Cyclic Silicone 24.0% by Mass Octyl methoxycinnamate 7.0 Titanium dioxide (hydrophobicized product) 10.0 Zinc oxide ( Hydrophobized product) 10.0 Talc (hydrophobized product) 4.0 Squalane 5.0 Dimethicone copolyol 2.0 Organically modified montmorillonite 0.5 Preservative proper amount Perfume proper amount (aqueous phase) Purified water 26.5 Dipropylene Glycol 7.0 3-O-ethylascorbic acid 1.0 Arbutin 3.0 (production method) An oil phase and an aqueous phase are mixed and dissolved. For the oil phase, titanium dioxide is sufficiently dispersed, the aqueous phase is added, and the mixture is emulsified using a homogenizer.

Example 12 Liquid cosmetic (and sheet cosmetic impregnated with the same) (Aqueous phase) Glycerin 10.0% by mass 1,3-butylene glycol 5.0 3-O-ethylascorbic acid 1.0 Xanthan gum 0.1 Carboxyvinyl polymer 0.1 Citric acid 0.1 Sodium citrate 0.2 Lactic acid 0.1 Trisodium edetate 0.1 Purified water Residue (alcohol phase) Ethanol 10.0 Polyoxyethylene polyoxypropylene decyl Tetradecyl ether 1.0 Fragrance Suitable amount (production method) Dissolve the water phase and alcohol phase uniformly,
The alcohol phase is added to the water phase and mixed homogeneously.

Example 13 Sunscreen (Oil Phase) Benton 38 (National Red Co.) 2.0% by Mass Isostearyl Alcohol 1.0 Cyclic Silicon 10.0 Trimethylsiloxysilicic Acid 5.0 Hydrophobized Titanium Oxide 5.0 Octyl Methoxycinnamic acid 10.0 Evening primrose oil 0.3 Spherical polyethylene 1.0 Tocopherol acetate 0.3 Vitamin A acetate 0.1 Perfume proper amount (water phase) 3-O-ethylascorbic acid 1.0 L-alanine 0.5 L -Arginine hydrochloride 1.0 1,3-butylene glycol 5.0 Methylparaben 0.2 Xylitol 8.0 Purified water Residue (manufacturing method) Add the water phase parts uniformly dissolved to the uniformly dispersed oil phase parts, and homomixer. After uniform dispersion in, a water-in-oil emulsion composition is obtained.

Example 14 W / O emulsion type emulsion (aqueous phase) isopropyl alcohol 10.0 mass% dipropylene glycol 2.0 potassium chloride 0.5 edetate 3 sodium 0.1 diisostearate diglyceryl 0.5 POE modified Dimethylpolysiloxane 1.0 3-O-ethylascorbic acid 2.0 Methylparaben 0.1 Ion-exchanged water Residue (oil phase) Octamethylcyclotetrasiloxane 25.0 Decamethylcyclopentasiloxane 15.0 Aminopropyldimethicone 3.0 Spherical polymethylmethacrylate 2.0 (average particle diameter 10 μm) Trimethylsiloxysilicic acid 5.0 Stearyl glycyrrhetinate 0.1 Eucalyptus oil 3.0 Fragrance Suitable amount (manufacturing method) Aqueous phase uniformly dissolved in uniformly dispersed oil phase Is added and homogenized with a homomixer. Disperse to obtain an emulsion.

Example 15 Lotion (with powder) Ethanol 30.0% by mass Isopropyl alcohol 10.0 Glycerin 1.0 Solbit 1.0 3-O-ethylascorbic acid 1.0 POE (20) oleyl alcohol ether 0. 5 Citric acid 0.1 Sodium citrate 0.4 Spherical anhydrous silicic acid (average particle size 1 μm) 0.5 Polyvinylpyrrolidone 0.01 Camphor 0.5 Disodium edetate 0.1 Zinc white 0.5 Allantoin 0.1 Fragrance 0.1 Purified water Residue (production method) Powder is uniformly dispersed in a part of water and added to the rest.

Example 16 Pack (aqueous phase) 1,3-butylene glycol 10.0 mass% sorbitol 5.0 propylene glycol 3.0 sodium metaphosphate 0.1 trisodium edetate 0.1 3-O-ethylascorbine Acid 1.0 Peony extract 0.1 (Powder phase) Zinc oxide 5.0 Kaolin 3.0 Bentonite 3.0 Titanium oxide 1.0 (Alcohol phase) Ethanol 5.0 Caustic potassium 0.2 Ethylparaben 0.1 (Production method ) The powder layer is added to the aqueous phase and uniformly mixed, then the alcohol phase is added and further uniformly mixed.

Example 17 Cream (Oil Phase) Retinol 0.2% by mass BHT 0.1 tetra-2-ethylhexanoate pentaerythritol 20.0 behenyl alcohol 1.5 ethylparaben 0.1 butylparaben 0.1 (aqueous phase) ) Trisodium edetate 0.1 3-O-ethylascorbic acid 1.0 Glycerin 5.0 POE (20) behenyl ether 3.0 Purified water Residue (manufacturing method) Residue (production method) Water phase uniformly dissolved in uniformly dispersed oil phase parts Add parts and uniformly disperse with a homomixer.

Example 18 Cream (oil phase) Benton 38 (National Red Co.) 2.0% by mass diglycerin diisostearate 1.0 cyclomethicone 10.0 vaseline 5.0 squalane 15.0 fragrance retinol 0.1 ( Aqueous phase) Dipropylene glycol 5.0 Methylparaben 0.2 Arginine 0.1 3-O-Ethylascorbic acid 1.0 Purified water Residue (production method) To a uniformly mixed oil phase, a uniformly dissolved aqueous phase was added. , Mix evenly with a homomixer.

Example 19 Emulsion (Oil Phase) Stearyl alcohol 1.0% by mass Squalane 3.0 Dimethylpolysiloxane 3.0 Trioctanoin 1.0 Isostearyl isostearate 0.5 Perfume Appropriate amount (water phase) Glycerin 5. 0 dipropylene glycol 2.0 sorbitol 3.0 3-O-ethylascorbic acid 1.0 carboxyvinyl polymer 0.3 acrylic acid / alkyl methacrylate copolymer 0.1 edetate disodium 0.1 polyacrylamide 0. 5 Sodium polyacrylate 0.5 Caustic potassium 0.1 Citric acid 0.1 Sodium citrate 0.2 (Production method) Add the uniformly dissolved aqueous phase parts to the uniformly dispersed oil phase parts, and disperse uniformly with a homomixer. To do.

[0042]

INDUSTRIAL APPLICABILITY As described above, according to the present invention, the colorless and transparent dihydroxyindole compound produced by the melanocytes present in the basal layer of the epidermis is directly exposed to UVA and polymerized to produce skin caused by melanin. By first finding that the blackening phenomenon is suppressed by 3-O-ethylascorbic acid, it is intended to provide a skin external preparation capable of effectively preventing blackening of the skin by UVA.

Continued front page    (72) Inventor Masato Hatao             2-2-1 Hayabuchi, Tsuzuki Ward, Yokohama City, Kanagawa Prefecture             Shiseido Research Center (Shin-Yokohama)             Within F-term (reference) 4C083 AA082 AA112 AA122 AB032                       AB152 AB172 AB212 AB232                       AB242 AB282 AB332 AB352                       AB432 AB442 AC012 AC022                       AC072 AC082 AC092 AC102                       AC122 AC132 AC182 AC242                       AC302 AC312 AC352 AC402                       AC422 AC432 AC442 AC472                       AC482 AC532 AC542 AC582                       AC622 AC642 AC682 AC712                       AC792 AD022 AD042 AD072                       AD092 AD112 AD152 AD162                       AD172 AD332 AD352 AD392                       AD512 AD532 AD622 AD641                       AD642 AD662 CC01 CC02                       CC04 CC05 CC07 CC12 CC19                       DD21 DD22 DD23 DD27 DD31                       DD32 EE03 EE17

Claims (3)

[Claims] 1. A polymerization inhibitor, which suppresses the polymerization of a dihydroxyindole compound in vivo caused by irradiation with long-wavelength ultraviolet light (UVA), which comprises 3-O-ethylascorbic acid. Inhibitor. 2. A skin external preparation containing the polymerization inhibitor according to claim 1. 3. A skin external preparation for immediate blackening prevention, which comprises the polymerization inhibitor according to claim 1.