JPH0543446A - Beautifying and whitening skin medicine for external use - Google Patents

Abstract

PURPOSE:To obtain a beautifying and whitening skin medicine for external use, containing one or more specific gentisic acid ester derivatives or further vitamin Cs or vitamin Es added thereto and having powerful skin decoloring, beautifying and whitening effects. CONSTITUTION:A beautifying and whitening skin medicine for external use is obtained by blending one or more gentisic acid derivatives (e.g. methyl gentisate) expressed by the formula (R is 1-20C straight-chain or branched saturated aliphatic hydrocarbon or arylalkyl) or further vitamin C or its derivative or vitamin E or its derivative with other ingredients. The gentisic acid derivative expressed by the formula is preferably 1-8C and blended in an amount of about 0.01-10wt.%. The gentisic acid derivative is a safe compound and capable of producing expected effects by using a small amount.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin which contains at least one gentisic acid ester derivative as an active ingredient and has remarkably improved skin bleaching effect.

[0002]

BACKGROUND OF THE INVENTION Although there are some unclear points about the mechanism of the occurrence of skin spots, etc., it is generally caused by abnormal hormones or irritation of ultraviolet rays from sunlight. It is believed that melanin pigment is formed, which is abnormally deposited in the skin. In treating such spots and bruises, substances that suppress the production of melanin,
For example, a method in which a large amount of vitamin C is administered, a method in which glutathione or the like is injected, or kojic acid, L-ascorbic acid and a derivative thereof (fatty acid, sulfuric acid, phosphate ester, etc.), cysteine or glutathione and a derivative thereof, etc. -A method such as applying it locally in the form of a mousse or lotion is adopted. In Europe and America, hydroquinone preparations are used as medicines. However, these compounds, except for hydroquinone, do not exhibit sufficient whitening effect because their effects are extremely slow to develop. On the other hand, with regard to hydroquinone, although its effect has been confirmed, its use is generally not permitted in Japan due to its sensitizing property. Therefore, in order to improve its safety, attempts have been made to use monoesters of higher fatty acids and alkyl monoethers (Japanese Patent Laid-Open No. 58-1545).
No. 07), but it cannot be said that the esters are safe because they are decomposed by a hydrolase in the body, and ethers have been obtained which are sufficiently satisfactory in terms of safety. Absent. Therefore, as a solution to these problems, the present inventors have proposed a gentisic acid ester derivative which is said to have an antioxidant action (Japanese Patent Application Laid-Open No. 1-28988).
As a result of extensive studies on these compounds, it has been found that these compounds, especially specific ones thereof, have a stronger skin decolorizing and whitening effect than hydroquinone and can be applied as a skin external preparation for whitening.

[0003]

[Means for Solving the Problems] That is, the present invention is a whitening skin external preparation containing at least one gentisic acid ester derivative represented by the following general formula 1.

[Chemical 2] (In the formula, R represents a linear or branched saturated aliphatic hydrocarbon group having 1 to 20 carbon atoms or an arylalkyl group.) Hereinafter, the constitution of the present invention will be described in detail.

The gentisic acid ester derivative used in the present invention is a substance represented by the above-mentioned general formula 1, and these compounds can be synthesized by a known synthesis method, for example, linear or branched alcohol and gentisic acid with an acid catalyst (p. -Toluenesulfonic acid, sulfuric acid, etc.) can be added and reacted to give a gentisic acid ester. Specific examples of the substance name are methyl gentisate ethyl gentisate propyl gentisate isopropyl gentisate butyl gentisate 2-butyl gentisate 2-methyl-1-propyl gentisate 2-methyl-2-propyl gentisate Pentyl gentisic acid 2-pentyl gentisic acid 3-pentyl gentisic acid tert-amyl gentisic acid 2-methyl-1-butyl gentisic acid 3-methyl-2-butyl gentisic acid neopentyl gentisic acid hexyl gentisic acid 2-hexyl gentisic acid 3-hexyl 2-Methyl-1-pentyl gentisate 2-Methyl-2-pentyl gentisate 2-Methyl-3-pentyl gentisate 3-Methyl-1-pentyl gentisate 3-Methyl-2-pentyl gentisate 3-methyl-3-pentyl gentisic acid 4-methyl-1-pentyl gentisic acid 4-methyl-2-pentyl gentisic acid heptyl gentisic acid 2-heptyl gentisic acid 3-heptyl gentisic acid 2,2-dimethyl-3-pentyl Pentyl gentisic acid 2,3-dimethyl-3-pentyl gentisic acid 2,4-dimethyl-3-pentyl gentisic acid 4,4-dimethyl-2-pentyl gentisic acid 3-ethyl-3-pentyl gentisic acid 2-methyl-2 -Hexyl gentisic acid 3-methyl-3-hexyl gentisic acid 5-methyl-2-hexyl gentisic acid 2-tetradecyl gentisic acid pentadecyl gentisic acid hexadecyl gentisic acid 2-hexadecyl gentisic acid heptadecyl gentisic acid octadecyl gentisic acid Nadeshiru gentisic acid eicosyl benzyl gentisic acid and the like. Of these, straight-chain or branched esters having 1 to 8 carbon atoms are desirable from the viewpoint of whitening effect and irritancy, and among them, those having up to 6 carbon atoms are particularly preferable. The compounding amount is 0.001-based on the total amount of the external preparation for skin.
It is 20% by weight, preferably 0.01 to 10% by weight.
If it is less than 0.001% by weight, the whitening effect is poor, and if it exceeds 20% by weight, the effect cannot be expected to increase.

Further, according to the present invention, at least one or more gentisic acid ester derivative represented by the above general formula 1 and vitamin C or a derivative thereof or vitamin E is used.
Alternatively, there is provided a whitening skin external preparation characterized by being blended with a derivative thereof. Vitamin C used in the present invention
Means L-ascorbic acid, which has cell respiration action, enzyme activation action, collagen formation action, and melanin reduction action due to its strong reducing action. Also, vitamin C
Examples of the derivative of L include: L-ascorbic acid monostearate, L-ascorbic acid monopalmitate, L
-L-ascorbic acid monoalkyl esters such as ascorbic acid monooleate, L-ascorbic acid monoester derivatives such as L-ascorbic acid monophosphate, L-ascorbic acid-2-sodium sulfate,
L-ascorbic acid dialkyl esters such as L-ascorbic acid-2,6-distearate, L-ascorbic acid-2,6-dipalmitate, L-ascorbic acid-2,6-diolate, L- L-ascorbic acid diester derivatives such as ascorbic acid diphosphate, L
Examples thereof include trialkyl esters such as ascorbic acid tristearate, L-ascorbic acid tripalmitate and L-ascorbic acid trioleate, and ascorbic acid triester derivatives such as L-ascorbic acid triphosphoric acid ester. In carrying out the present invention,
From these, one kind or two or more kinds are appropriately selected and mixed.

The vitamin E and its derivative used in the present invention include α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, tocopheryl acetate and tocopherol nicotinate. Are exemplified. In the present invention, any one kind or two or more kinds are selected from these and used. These vitamin Es may be naturally derived or synthetic products. When using naturally-occurring vitamin E (d-α-tocopherol), crude vitamin E or a purified product may be used. In addition to tocopherol, for example, triglyceride, lecithin,
Vitamin K, vitamin A, ubiquinone, etc. may be contained. The blending amount of vitamin Cs and vitamin Es is about 0.01 to 5% by weight, preferably 0.05 to 3% by weight, based on the total amount of the skin external preparation. The external preparation for skin containing vitamin C or vitamin E according to the present invention has an increased whitening effect as compared with the case where the gentisic acid ester derivative is used alone. It is considered that this is because vitamin C or E enhances the absorbency to the skin.

The external preparation for skin of the present invention contains, in addition to the above-mentioned essential components, other components which are usually used in external preparations for skin such as cosmetics and pharmaceuticals, such as oil, ultraviolet absorber, antioxidant and surfactant. , Moisturizers, fragrances, water, alcohols, thickeners, coloring materials, skin nutrients (pantothenethyl ether, glycyrrhizinate) and the like can be appropriately added as necessary. Among these, as the ultraviolet absorber, as a benzoic acid-based one, para-aminobenzoic acid (hereinafter referred to as PA) is used.
(Abbreviated as BA), glyceryl PABA, ethyldihydroxypropyl PABA, cinnamic acid type octyl methoxycinnamate, 2-ethoxyethyl-p-methoxycinnamate, benzophenone type
2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-
Methoxy-4-methylbenzophenone, as other, urocanic acid ethyl ester, 2-phenyl-5
-Methylbenzoxazol, 4-methoxy-4-t-butyldibenzoylmethane and the like are used.

[0008]

EXAMPLES Next, 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 weight. First, a synthetic example of the derivative used in the present invention will be described in detail. Synthesis Example 1 (n-hexyl gentisic acid) 15.4 g (0.1 mo of gentisic acid) under a nitrogen atmosphere.
1) and n-hexyl alcohol 12.3 g (0.12 m
ol) and 0.4 g of p-toluenesulfonic acid were suspended in 100 ml of xylene and reacted at 140 ° C. for 24 hours while stirring. After completion of the reaction, the solution was washed with 10 ml of a saturated aqueous solution of sodium hydrogencarbonate and then with distilled water, the xylene layer was dried over anhydrous sodium sulfate, and xylene was removed under reduced pressure to give the ester 2 as a pale yellow transparent viscous oil.
1.8 g (yield 91.6%) was obtained. Infrared absorption spectrum KBr (liquid film): 3292, 2957, 2932, 2
860, 1678, 1487, 1467, 1404, 1
080 (cm ^-1 )

Synthesis Example 2 (3-Methyl-1 gentisate-1
-Butyl) Under nitrogen atmosphere, 10.8 g (0.07 mo) of gentisic acid
l) and 7.1 g of 3-methyl-1-butanol (0.08)
mol) and 0.5 g of p-toluenesulfonic acid are suspended in 100 ml of xylene and stirred at 140 ° C. for 48 hours.
After reacting for a period of time, 15.3 g (yield 97%) of the ester was obtained as a viscous oil in the same manner as in Synthesis Example 1. Infrared absorption spectrum KBr (liquid film): 3418, 2960, 2
932, 1678, 1620, 1489, 1467, 1
082 (cm ^-1 )

Synthesis Example 3 (2-ethylhexyl gentisate) In a nitrogen atmosphere, 7.7 g (0.05 mo) of gentisic acid was used.
l) and 7.8 g of 2-ethylhexanol (0.06 mo
1) and p-toluenesulfonic acid (0.4 g) were suspended in 100 ml of xylene and reacted with stirring at 140 ° C. for 10 hours to give 11.4 g (yield) of the ester as a viscous oil in the same manner as in Synthesis Example 1. 85%). Infrared absorption spectrum KBr (liquid film): 3408, 2960, 293
0,2874,1678,1620,1487,146
6,1080 (cm ^-1 )

Examples 1 to 6 and Comparative Examples 1 and 2 (alcohol phase) 95% ethyl alcohol 55.0 polyoxyethylene (25 mol) 2.0 hardened castor oil ether antioxidant / preservative Appropriate amount Perfume Appropriate amount Drug (described in Table 1) 1.0 (Aqueous phase) 5.0 Glycerin 5.0 Sodium hexametaphosphate Appropriate amount Ion-exchanged water Residual production method A water phase and an alcohol phase are prepared and then solubilized.

Test Method for Whitening Effect 70 subjects, exposed to sunlight in summer for 4 hours (2 hours per day for 2 days), conducted from 5 days after the day of exposure to sunlight to the skin of the upper arm inner skin The samples of Examples 1-6 and Comparative Examples 1-2 were applied once in the morning and in the evening for 8 weeks. Group of 10 panels
The test was conducted by dividing the names into 5 groups. Judgment of whitening effect ⊚: When the ratio of markedly effective and effective among the subjects is 80% or more ○: The ratio of markedly effective and effective among the subjects is 50 to 8
In the case of 0% △: The ratio of markedly effective and effective among the subjects is 50 to 3
In the case of 0% x: In the case where the ratio of markedly effective and effective in the subjects is 30% or less Table 1 shows the results based on the above criteria.

[0013]

[Table 1] ─────────────────────────────────── Compound name Whitening effect ──────── ──────────────────────────── Comparative Example 1 None × Comparative Example 2 Hydroquinone Δ Example 1 Methyl gentisate ◎ Example 2 Genticic acid Decyl ○ Example 3 Eicosyl gentisate ○ Example 4 2-Ethyl-hexyl gentisate ◎ Example 5 2-Hexadecyl gentisate ○ Example 6 3-Methyl-1-butyl gentisate ◎ ───────── ─────────────────────────── As is clear from Table 1, the effect after exposure to sunlight is greater than that of the comparative example. It was observed that the examples prevent the deposition of excess melanin pigment and prevent darkening.

Example 7 (Cream) Stearic acid 5.0 Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Hexyl gentisate 20 0.0 Caustic potassium 0.2 Sodium bisulfite 0.01 Preservative proper amount Perfume proper amount Ion-exchanged water Residual production method Propylene glycol and caustic potash are added to ion-exchanged water, dissolved and heated to 70 ° C. (water phase). The other ingredients are mixed, melted by heating and kept at 70 ° C (oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is kept for a while to cause the reaction. After that, homomixer
Emulsify uniformly with and cool to 30 ° C with good stirring.

Example 8 (Cream, Vitamin C Blend) Stearic Acid 6.0 Sorbitan Monostearate 2.0 Polyoxyethylene (20 mol) Sorbitan Monostearate 1.5 Propylene Glycol 10. 0 gentisic acid propyl 5.0 glycerin trioctanoate Noe - DOO 10.0 squalene 5.0 vitamin C 0.1 sodium bisulfite 0.001 ethylparaben 0.3 perfume qs ion exchanged water balance preparation propylene glycol in deionized water - And vitamin C are added and heated to 70 ° C. (water phase). The other ingredients are mixed, melted by heating and kept at 70 ° C (oil phase). The oil phase is added to the aqueous phase, preliminary emulsification is performed, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring. The obtained external preparation for skin was more excellent in whitening effect than that of the formulation not containing vitamin C.

Example 9 (Cream, Vitamin E Blend) Stearyl Alcohol 7.0 Stearic Acid 2.0 Hydrogenated Lanolin 2.0 Squalane 5.0 2-Octyldodecyl Alcohol 6.0 Polyoxy Ethylene (25 mol) Cetyl alcohol ether 3.0 Glycerine monostearate ester 2.0 Propylene glycol 5.0 Methyl gentisate 0.01 Vitamin E (dl-α-tocopherol) 0.05 Perfume proper amount Hydrogen bisulfite Sodium 0.03 Ethylparaben 0.3 Ion-exchanged water Propylene glycol is added to the residual production-method ion-exchanged water, and the mixture is heated and kept at 70 ° C. (aqueous phase). The other ingredients are mixed, melted by heating and kept at 70 ° C (oil phase). The oil phase is added to the aqueous phase, preliminary emulsification is performed, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring. The obtained external preparation for skin is
The whitening effect was superior to that of the prescription containing no vitamin E.

Example 10 (Cream) Solid paraffin 5.0 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 2-Pentyl gentisate 0.05 3-Methyl-1-butyl gentisate 0.05 Ion-exchanged water Residual fragrance Sodium bisulfite 0.03 Ethylparaben 0.3 Process ion Add soap powder and borax to exchange water, heat and dissolve
Keep at 0 ° C (aqueous phase). The other ingredients are mixed, melted by heating and kept 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 11 (Emulsion) Stearic acid 2.5 Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) Monooleate ester 2.0 Polyethylene glycol 1500 3. 0 Triethanolamine 1.0 Dodecyl gentisate 0.001 Sodium bisulfite 0.01 Ethylparaben 0.3 Carboxyvinyl polymer 0.05 (Product name: Carbopol 941, BFGoodrich Chemical company) Perfume Amount Ion Exchanged water Residual production method 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, melted by heating and kept at 70 ° C (oil phase). The oil phase is added to the aqueous phase, preliminary emulsification is performed, phase A is added, the mixture is uniformly emulsified with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

Example 12 (Emulsion, UV absorber blend) (Oil phase part) Stearyl alcohol 1.5 Squalene 2.0 Vaseline 2.5 Deodorized liquid lanolin 1.5 Evening primrose oil 2.0 Isopropyl myristate 5 0.0 Glycerin monooleate 2.0 Polyoxyethylene (60 mol) hydrogenated castor oil 2.0 Tocopheryl acetate 0.05 Ethylparaben 0.2 Butylparaben 0.1 3-Methyl-3-pentyl gentisate 1 .0 Para-aminobenzoic acid 0.1 Perfume proper amount (water phase part) sodium bisulfite 0.001 glycerin 5.0 sodium hyaluronate 0.01 carboxyvinyl polymer 0.2 (trade name: Carbopol 941, BFGoodrich Chemical company) Potassium hydroxide 0.2 Purified water Dissolve the residual oil phase in the production method at 70 ° C. The water phase part is melted at 70 ° C., the oil phase part is mixed with the water phase part, the mixture is emulsified by an emulsifier, and then cooled to 30 ° C. by a heat exchanger.

Example 13 (Emulsion) Microcrystalline wax 1.0 Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 Polyoxyethylene (20 mol) Sorbitan mono Oleic acid ester 1.0 Propylene glycol 7.0 2,6-Dimethyl-4-heptyl gentisate 3.0 Ethylparaben 0.3 Sodium hydrogensulfite 0.01 Fragrance Ion-exchanged water Residual production method Propylene to ion-exchanged water Add glycol and heat to maintain 70 ° C (aqueous phase). The other ingredients are mixed, dissolved by heating and kept at 70 ° C. (oil phase). While stirring the oil phase, gradually add the aqueous phase to this and homogenize with a homomixer.
After emulsification, cool to 30 ° C while stirring well.

Example 14 (Jelly) 95% Ethyl alcohol 10.0 Dipropylene glycol 15.0 Polyoxyethylene (50 mol) Oleyl alcohol ether 2.0 Carboxyvinyl polymer 1.0 ( Product name: Carbopol 940, BFGoodrich Chemical company) Caustic soda 0.15 L-arginine 0.1 Eicosyl gentisate 0.05 2-Hydroxy-4-methoxybenzophenone sodium sulfonate 0.05 Methylparaben 0 .2 ethylenediaminetetraacetic a Sete - DOO, trisodium dihydrate 0.05 mosquitoes in perfume qs ion-exchanged water balance preparation of ion-exchanged water - ball port - uniformly dissolved Le 940, whereas, 95% ethanol - Le Dissolve eicosyl gentisate, polyoxyethylene (50 mol) oleyl alcohol ether, It is added to the phase. Next, after adding other components, the mixture is neutralized with caustic soda and L-arginine to thicken it.

Example 15 (Beauty liquid) (Phase A) Ethanol (95%) 10.0 Polyoxyethylene (20) Octyldodecanol 1.0 Methylparaben 0.15 Pantothenylethyl ether 0.1 Hexyl gentisate 0.05 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Cypropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 (trade name: mosquito) -Bopol 940, BFGoodrich Chemical company) Purified water Residual production method Phases A and C are uniformly dissolved, and phase A is added to phase C to solubilize it. Then, after adding phase B, filling is performed.

Example 16 (pack, vitamin E blend) (A phase) dipropylene glycol 5.0 polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (B phase) octyl gentisate 1.0 1.0 gentisin Acid 2-tetradecyl 1.0 Octadecyl gentisate 1.0 Olive oil 5.0 Vitamin E (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 Residual production method Phase A, Phase B, Phase C are uniformly dissolved, and Phase B is added to Phase A. In addition, it is solubilized. Next, this is added to phase C and then filled.

Example 17 (pack containing powder) (alcohol phase) 95% ethanol 10.0 propylene glycol 5.0 2-hexadecyl gentisate 10.0 isopropyl gentisate 1.0 perfume proper colorant Appropriate amount (aqueous phase) Zinc white 25.0 Kaolin 20.0 Methylparaben 0.3 Glycerin 5.0 Ion-exchanged water Residual production method The aqueous phase is uniformly adjusted at room temperature. Then, the alcohol phase prepared at room temperature is added and mixed uniformly.

Example 18 (Cream) Solid paraffin 5.0 Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) sorbitan monolaurate 2.0 Soap powder 0.1 Borax 0.2 Benzyl gentisate 0.05 Ion-exchanged water Residual fragrance Sodium bisulfite 0.03 Ethylparaben 0.3 Method Soap powder and borax are added to ion-exchanged water and dissolved by heating 7
Keep at 0 ° C (aqueous phase). The other ingredients are mixed, melted by heating and kept at 70 ° C (oil phase). The oil phase is stirred into the water phase and gradually added to carry out the reaction. After completion of the reaction, the mixture is uniformly emulsified with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

[0026]

As described above, since the gentisic acid ester derivative used in the present invention has a stronger whitening effect than conventional ones, it can be used in a small amount to achieve desired effects and is safe. It is a compound. Therefore, by blending the compound, a whitening skin external preparation having excellent properties is provided.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Masako Naganuma Masako Naganuma, 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Shiseido Research Institute Co., Ltd. Shiseido Institute

Claims (2)

[Claims] 1. A whitening skin external preparation comprising one or more gentisic acid ester derivatives represented by the following general formula. [Chemical 1] (In the formula, R represents a linear or branched saturated aliphatic hydrocarbon group having 1 to 20 carbon atoms or an arylalkyl group.) 2. A whitening skin external preparation, comprising at least one or more of the gentisic acid ester derivative according to claim 1 and vitamin C or a derivative thereof or vitamin E or a derivative thereof.