JPH07173046A - Dermal agent for external use - Google Patents

Abstract

PURPOSE:To obtain a high-safety dermal agent for external use, containing a specified hydroxysalicylic acid (fatty acid ester) glycoside and excellent in skin-whitening effect and improvement of rough skin. CONSTITUTION:This dermal agent for external use contains 0.001 to 20wt.% hydroxysalicylic acid glycoside of the formula (R1 is H or a 1 to 20C hydrocarbon; one of R2 and R3 is sugar residue and the other is H) and/or a hydroxysalicylic acid fatty acid ester glycoside (e.g. a 2-beta-D-glycosyloxy-5- hydroxybenzoic acid ester). The glycoside can be synthesized, e.g. by reacting hydroxysalicylic acid (ester) with an acetylated sugar such as pentaacetyl glucose in the presence of an acid catalyst.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin external preparation, particularly to a skin external preparation having an excellent whitening effect.

[0002]

BACKGROUND OF THE INVENTION Although there are some unclear points regarding the mechanism of skin stains and the like, melanin pigments are generally formed due to hormonal abnormalities and stimulation of ultraviolet rays from the sun, It is thought that it will be abnormally deposited. Treatments for such spots and bruises include a substance that suppresses the production of melanin, for example, a method of orally administering a large amount of vitamin C, a method of injecting glutathione or the like, or an ointment, a cream of kojic acid, vitamin C, cysteine, etc.
A method such as applying it locally in the form of lotion or the like is adopted. In Europe and America, hydroquinone preparations are used as medicines.

[0003]

However, the effect of these compounds is extremely slow except for the hydroquinone preparation, so that a sufficient whitening effect cannot be obtained. On the other hand, although the effect of hadroquinone is tentatively recognized, its use is generally limited because of its sensitizing property.

In recent years, attempts have been made to use alkyl monoethers, which are higher alcohols, for the purpose of improving the safety of hydroquinone, but in the present circumstances, those having sufficient safety have not yet been obtained. The present invention has been made in view of the above problems of the prior art, and an object thereof is to provide a whitening agent having an excellent whitening effect and safety, or a skin external preparation containing the same.

[0005]

Means for Solving the Problems As a result of intensive studies for achieving the above-mentioned object, the present inventors have found that a specific glycoside among glycosides of hydroxysalicylic acid or glycosides of hydroxysalicylic acid aliphatic ester It has been found that the body has a stronger whitening effect than hydroquinone, and that by blending these, a skin external preparation excellent in whitening effect and safety can be obtained.

That is, the external preparation for skin according to claim 1 of the present invention is at least one glycoside of hydroxysalicylic acid and / or glycoside of hydroxysalicylic acid aliphatic ester represented by the following general formula 2. It is characterized by containing the above.

[Chemical 2] (In the formula, R ₁ represents hydrogen or a saturated hydrocarbon group having 1 to 20 carbon atoms or an unsaturated hydrocarbon group, which hydrocarbon group may be linear or branched. One of R _{2 and} R ₃ Is a sugar residue and the other represents hydrogen.)

The present invention will be described in detail below. The glycoside of hydroxysalicylic acid or the glycoside of hydroxysalicylic acid ester used in the present invention is a substance represented by the above general formula 2, wherein R ₁ is hydrogen or a saturated hydrocarbon group having 1 to 20 carbon atoms or It represents an unsaturated hydrocarbon group, and the hydrocarbon group may be linear or branched. The branched unsaturated hydrocarbon group includes aromatic hydrocarbon groups such as phenyl group and benzyl group. In the chemical formula ₂ , one of R _{2 and} R ₃ is a sugar residue and the other is hydrogen, and such sugar residues include a 5-carbon sugar residue, a 6-carbon sugar residue, and an amino sugar residue. Group, a uronic acid sugar residue.

The compound of the present invention is obtained by reacting, for example, hydroxysalicylic acid or hydroxysalicylic acid ester with an acetylated product of sugar such as pentaacetylglucose (or acetobrominated product of sugar such as acetobromoglucose) in the presence of an acid catalyst. By doing so, a hydroxysalicylic acid glycoside or a hydroxysalicylic acid ester glycoside can be obtained. It can also be obtained by condensing a hydroxysalicylic acid ester and pentaacetyl glucose as in a known synthesis method (Arch. Pharm., 291 (1958)).
Specific examples of the substance name are: 3-β-D-glucopyranosyloxysalicylic acid methyl 3-β-D-glucopyranosyloxysalicylate 3-β-D-glucopyranosyloxysalicylate ethyl 3- Propyl β-D-glucopyranosyloxysalicylate 3-β-D-Glucopyranosyloxysalicylate isopropyl 4-β-D-glucopyranosyloxysalicylate 4-β-D-glucopyranosyloxysalicylate Methyl 4 Ethyl 4-β-D-Glucopyranosyloxysalicylate Propyl 4-β-D-Glucopyranosyloxysalicylate Isopropyl 4-β-D-Glucopyranosyloxysalicylate 5-β-D-Glucopyranosyloxysalicylate Methyl 5-β-D-glucopyranosyloxysalicylate 5-β-D-Glucopyranosyloxysalicylate Ethyl acid 5-β-D-glucopyranosyloxysalicylate propyl 5-β-D-glucopyranosyloxysalicylate isopropyl 6-β-D-glucopyranosyloxysalicylate 6-β-D-glucopyranosyl Methyl oxysalicylate 6-β-D-Glucopyranosyl oxysalicylate Ethyl 6-β-D-Glucopyranosyl oxysalicylate propyl 6-β-D-Glucopyranosyl oxysalicylate isopropyl 2-β-D-glucopyra Nosyloxy-3-hydroxybenzoic acid 2-β-D-glucopyranosyloxy-3-hydroxybenzoic acid methyl 2-β-D-glucopyranosyloxy-3-hydroxybenzoic acid ethyl 2-β-D -Propyl glucopyranosyloxy-3-hydroxybenzoate 2-β-D-glucopyranosyloxy-3-hydr Isopropyl oxybenzoate 2-β-D-glucopyranosyloxy-4-hydroxybenzoic acid Methyl 2-β-D-glucopyranosyloxy-4-hydroxybenzoate 2-β-D-glucopyranosyloxy Ethyl-4-hydroxybenzoate 2-β-D-glucopyranosyloxy-4-hydroxybenzoic acid propyl 2-β-D-glucopyranosyloxy-4-hydroxybenzoic acid isopropyl 2-β-D-gluco Pyranosyloxy-5-hydroxybenzoic acid 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid methyl ester 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid ethyl 2-β- Propyl D-glucopyranosyloxy-5-hydroxybenzoate 2-β-D-Glucopyranosyloxy-5-hydroxybenzoic acid isopropylate 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 irritation, and among them, those having up to 6 carbon atoms are particularly preferable.

Among the hydroxysalicylic acid ester glycosides of the present invention, 2-β- represented by the following general formula 3
It was revealed that D-glycosyloxy-5-hydroxybenzoic acid esters (hereinafter referred to as gentisic acid ester glycosides) have a whitening effect as well as a rough skin improving effect.

[Chemical 3] (In the formula, R ₁ represents a saturated hydrocarbon group having 1 to 20 carbon atoms or an unsaturated hydrocarbon group, which hydrocarbon group may be linear or branched. R ₂ is a 5-carbon sugar residue, Represents one selected from a 6-carbon sugar residue, an amino sugar residue, and a uronic acid sugar residue.)

Specific examples of such gentisic acid ester glycosides include, in addition to the above-described 2-β-D-glycosyloxy-5-hydroxybenzoic acid esters,
Butyl 2-β-D-glucopyranosyloxy-5-hydroxybenzoate, 2-methyl-1-propyl 2-β-D-glucopyranosyloxy-5-hydroxybenzoate,
2-β-2-D-Glucopyranosyloxy-5-hydroxybenzoic acid 2-methyl-2-propyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid pentyl, 2-β-D- 2-Pentyl glucopyranosyloxy-5-hydroxybenzoate, 3-pentyl 2-β-D-glucopyranosyloxy-5-hydroxybenzoate, 2
-Β-D-glucopyranosyloxy-5-hydroxybenzoic acid tert.-amyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid 2-methyl-1-butyl, 2-β- 2-Methyl-2-butyl D-glucopyranosyloxy-5-hydroxybenzoate, neopentyl 2-β-D-glucopyranosyloxy-5-hydroxybenzoate, 2-β-D-glucopyranosyl Hexyl oxy-5-hydroxybenzoate, 2-β-1-D-glucopyranosyloxy-5-hydroxybenzoic acid 2-methyl-1-
Pentyl, 2-β-D-glucopyranosyloxy-5-
2-Methyl-2-pentyl hydroxybenzoate, 2-β
2-Methyl-3-pentyl-D-glucopyranosyloxy-5-hydroxybenzoate, 3-methyl-1 2-β-D-glucopyranosyloxy-5-hydroxybenzoate
-Pentyl, 2-β-D-glucopyranosyloxy-5
-Hydroxybenzoic acid 3-methyl-2-pentyl, 2-
3-Methyl-3-pentyl β-D-glucopyranosyloxy-5-hydroxybenzoate, 4-methyl-2-β-D-glucopyranosyloxy-5-hydroxybenzoate
1-pentyl, 2-β-D-glucopyranosyloxy-
4-Methyl-2-pentyl 5-hydroxybenzoate, 2
-Β-D-Glucopyranosyloxy-5-hydroxybenzoic acid heptyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid 2-heptyl, 2-β-D-
Glucopyranosyloxy-5-hydroxybenzoic acid 3-
Heptyl, 2-β-D-glucopyranosyloxy-5-
2,2-dimethyl-3-pentyl hydroxybenzoate,
2-β-D-Glucopyranosyloxy-5-hydroxybenzoic acid 2,3-dimethyl-3-pentyl, 2-β-D
-Glucopyranosyloxy-5-hydroxybenzoic acid 2,4-dimethyl-3-pentyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid 4,4-dimethyl-2-pentyl, 2 -Β-D-Glucopyranosyloxy-5-hydroxybenzoic acid 3-ethyl-3-pentyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid 3-methyl-3-hexyl, 2 -Β-D
-Glucopyranosyloxy-5-hydroxybenzoic acid 3
-Methyl-3-hexyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid 5-methyl-2-hexyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid 2 -Tetradecyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid pentadecyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid hexadecyl, 2-β-D-glucopyrano 2-hexadecyl siloxy-5-hydroxybenzoate, heptadecyl 2-β-D-glucopyranosyloxy-5-hydroxybenzoate, octadecyl 2-β-D-glucopyranosyloxy-5-hydroxybenzoate, Two
-Β-D-Glucopyranosyloxy-5-hydroxybenzoic acid nonadecyl, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid eicodecyl, 2-β-D
Benzyl glucopyranosyloxy-5-hydroxybenzoate and the like.

Of these gentisic acid ester glycosides, R ₁ is preferably a linear or branched ester having 1 to 8 carbon atoms from the viewpoints of whitening effect and rough skin improving effect, and among them, especially those having up to 6 carbon atoms. Is preferred.

The amount of hydroxysalicylic acid glycoside or hydroxysalicylic acid ester glycoside according to the present invention is 0.001 to 20% by weight based on the total amount of the external preparation for skin.
It is 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, at least one or more of the glycosides of hydroxysalicylic acid or the glycosides of hydroxysalicylic acid ester represented by the general formula 2 and vitamin C or a derivative thereof or vitamin E or a derivative thereof are blended. As a result, the whitening effect is increased as compared with the case where a hydroxysalicylic acid glycoside or a hydroxysalicylic acid ester glycoside is used alone. It is considered that this is because vitamin C or vitamin E increased the absorbency into the skin.

Vitamin C used in the present invention means L-ascorbic acid, which has a cell respiration action, an enzyme activation action, a collagen formation action and a melanin reduction action due to its strong reducing action. Examples of the vitamin C derivative include L-ascorbic acid monostearate and L
L-ascorbic acid monoalkyl ester such as ascorbic acid monopalmitate, L-ascorbic acid monooleate, L-ascorbic acid monoester derivative such as L-ascorbic acid monophosphate magnesium, L-ascorbic acid-2-sodium sulfate , L-ascorbic acid-2,6-dipalmitate, L-ascorbic acid dialkyl esters such as L-ascorbic acid-2,6-diolate, L-ascorbic acid diester derivatives such as L-ascorbic acid diphosphate, L -L such as ascorbic acid tristearate, L-ascorbic acid tripalmitate, L-ascorbic acid trioleate
Examples include L-ascorbic acid triester derivatives such as ascorbic acid trialkyl esters and L-ascorbic acid triphosphate. As the vitamin C used in the present invention, one kind or two or more kinds are appropriately selected and mixed from these.

The vitamin E and its derivatives used in the present invention include α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol,
Examples include tocopherol acetate, tocopherol nicotinate, and the like, and one or more of these are appropriately selected and mixed. These vitamin Es may be naturally derived or synthetic products. Vitamin E of natural origin (d-α-
When tocopherol) is used, it may be crude vitamin E or a purified product.

In the external preparation for skin of the present invention, vitamin C
0.0001 to 10% by weight, preferably 0.001 to 3% by weight, based on the total amount of the external preparation for skin, and the amount of vitamin Es added is 0.0001 to 5% by weight, based on the total amount of the external preparation for skin.
It is preferably 0.001 to 1% by weight. In addition to the above-mentioned essential components, the external preparation for skin of the present invention usually contains other components such as oil, which are used for external preparations for skin such as cosmetics and pharmaceuticals.
UV absorbers, antioxidants, surfactants, moisturizers, fragrances, water, alcohols, thickeners, coloring agents, skin nutritional agents (pantotenyl ethyl ether, glycyrrhizinate, etc.) are blended as necessary. be able to.

Among these, as the ultraviolet absorber, a benzoic acid-based one, para-aminobenzoic acid (hereinafter referred to as PABA) is used.
Abbreviated), glyceryl PABA, ethylhydroxypropyl PABA, cinnamic acid-based octylmethoxycinnamate, 2-methyl-p-methoxycinnamate, benzophenone-based 2,4-dihydroxybenzophenone, 2-hydroxy -4-methoxy-
4-Methylbenzophenone and urocanic acid ethyl ester, 2-phenyl-5-methylbenzoxazole, 4-methoxy-4-t-butyldibenzoylmethane and the like are used as others.

[0018]

The present invention will be described in more detail with reference to examples, but the present invention is not limited thereto. Unless otherwise specified, the blending amount is% by weight.

Examples 1 to 7 and Comparative Examples 1 to 2 Lotions were prepared according to the following formulations and whitening effect tests were conducted. (Alcohol phase) 95% Ethyl alcohol 55.0 Polyoxyethylene (25 mol) 2.0 Hardened castor oil ether Antioxidant / preservative Appropriate amount Perfume Appropriate amount Drug (listed in Table 1) 1.0 (Water phase) Glycerin 5.5 Sodium hexametaphosphate Suitable amount Ion-exchanged water Residual production method After preparing the aqueous phase and alcohol phase, solubilize them.

[0020]

[Table 1] ──────────────────────────────────── Compound ────────── ─────────────────────────── Comparative Example 1 None Comparative Example 2 Hydroquinone Example 1 5-β-D-glucopyranosyloxysalicylic acid Methyl ester Example 2 5-β-D-glucopyranosyloxysalicylic acid ethyl ester Example 3 4-β-D-glucopyranosyloxysalicylic acid methyl ester Example 4 4-β-D-glucopyranosyloxy Butyl salicylate Example 5 4-β-D-glucopyranosyloxysalicylic acid octyl ester Example 6 3-β-D-glucopyranosyloxysalicylic acid decyl ester Example 7 2-β-D-glucopyranosyl Oxy-5-hydroxy benzoate Acid methyl ester ────────────────────────────────────

Test Method for Whitening Effect For the skin of the inner part of the upper arm of 90 subjects exposed to sunlight in summer for 4 hours (2 hours per day for 2 days), 5 days after the day of exposure to sunlight The samples of Examples 1 to 7 and Comparative Examples 1 and 2 were applied once in the morning and evening once for 8 weeks. Panel 1 group 1
The test was carried out by dividing into 0 people into 9 groups.

Evaluation method The lightening effect after use was judged based on the following judgment criteria. Judgment of whitening effect ⊚: 80% of the subjects showed excellent efficacy and efficacy
In the above cases ○: 50% of the subjects showed excellent response and efficacy
In the case of 80% or more and Δ: 30% or more of the subjects exhibiting excellent response and efficacy
In the case of 50% or more and less than x: 30% of the subjects show excellent efficacy and efficacy
Table 2 shows the results based on the above criteria.

[0023]

[Table 2]

As is clear from Table 2, the effect after exposure to sunlight is that in Examples, as compared with Comparative Example, excessive deposition of melanin pigment can be prevented and darkening can be prevented. Admitted. Examples 8 to 13 and Comparative Examples 1 to 2 Of the glycosides of the present invention, the same formulation as in the whitening effect test of Examples 1 to 7 above was used for the gentisic acid ester glycoside using the agents shown in Table 3 below. A lotion was prepared in the above, and a whitening effect test and the following rough skin improving effect test were conducted.

[0025]

[Table 3] ──────────────────────────────────── Compound ────────── ─────────────────────────── Comparative Example 1 None Comparative Example 2 Hydroquinone Example 8 2-β-D-glucopyranosyloxy- 5-Hydroxybenzoic acid methyl ester Example 9 2-β-D-Glucopyranosyloxy-5-hydroxybenzoic acid ethyl ester Example 10 2-β-D-Glucopyranosyloxy-5-hydroxy butyl benzoate Ester Example 11 2-β-D-glucopyranosyloxy-5-hydroxy benzoic acid octyl ester Example 12 2-β-D-glucopyranosyloxy-5-hydroxy benzoic acid decyl ester Example 13 2- β-D-glucopyranosyloxy-5-hydr Carboxymethyl benzoic acid 2-hexadecyl ester ────────────────────────────────────

Test method for skin roughening improving effect This test was carried out by 80 subjects suffering from skin roughness or hot flashes after sunburn, and the test lotion was applied to the face.
After a week, the skin condition was visually evaluated. Further, a test lotion was applied to 80 male subjects who had razor removal immediately after shaving, and the effect on razor application was determined.
The evaluation criteria are as follows.

Improvement effect on rough skin Effectiveness: Those with disappearance of symptoms Effective: Those with weakened symptoms Somewhat effective: Those with slightly weakened symptoms Ineffective: Those with no change in symptoms

Improvement effect on razor shavings Remarkable effect: razor shavings disappeared Effective: razor shavings significantly improved Slightly effective: razor shavings slightly improved Ineffective: razor shavings did not change

Judgment ⊚: Effective and slightly effective ratio (effective ratio) of subjects is 80% or more. ○: Effective and slightly effective ratio (effective ratio) of subjects is 50% or more and less than 80%. △ : Effective and slightly effective rate (effective rate) of subjects is 30% or more and less than 50% ×: Effective or slightly effective rate (effective rate) of subject is less than 30% based on criteria The results are shown in Table 4.

[0030]

[Table 4] ──────────────────────────── Whitening effect Skin roughening improvement effect ────────────── Comparative Example 1 × × Comparative Example 2 △ × Example 8 ◎ ◎ Example 9 ○ ◎ Example 10 ◎ ○ Example 11 ◎ △ Example 12 ○ △ ─────────────── Example 13 ◎ × ─────────────────────────────

As is clear from Table 4, the effect after exposure to sunlight is greater in Example than in Comparative Example, in that excessive deposition of melanin pigment can be prevented and darkening can be prevented. Admitted. Moreover, the effect was recognized also for rough skin improvement.

Example 14 (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 5-β-D-glucopyranosyloxysalicylic acid 2-pentyl ester 0.05 4-β-D-glucopyranosyloxysalicylic acid 3-methyl-1-butyl ester 0. 05 Fragrance Suitable amount Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Ion-exchanged water Residual

Manufacturing method Soap powder and borax are added to ion-exchanged water and heated to 70 ° C. (water 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 while stirring, and the reaction is carried out. 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. The cream obtained in this formulation example had an excellent whitening effect.

Example 15 (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 Triethanol Amine 1.0 2-β-D-Glucopyranosyloxy-3-hydroxybenzoic acid isopropyl ester 0.001 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Carboxyvinyl polymer 0.05 (trade name: Carbopol 941 , BFGoodrich Chemical Company) Fragrance, appropriate amount, ion-exchanged water, residual

Manufacturing 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 uniformly emulsified with a homomixer. After emulsification, the mixture is cooled to 30 ° C. with thorough stirring. The emulsion obtained in this formulation example had an excellent whitening effect.

Example 16 (Emulsion) (Oil Phase Part) Stearyl alcohol 1.5 Squalane 2.0 Vaseline 2.5 Deodorizing liquid lanolin 1.5 Evening primrose oil 2.0 Isopropyl myristate 5.0 Glycerin monooleate 2. 0 polyoxyethylene (60 mol) hydrogenated castor oil 2.0 tocopherol acetate 0.05 ethylparaben 0.2 butylparaben 0.1 6-β-D-glucopyranosyloxysalicylic acid 1.0 paraaminobenzoic acid 0.1 Fragrance Suitable amount (water phase part) Sodium hydrogen sulfite 0.001 Glycerin 5.0 Sodium hyaluronate 0.01 Carboxyvinyl polymer 0.02 (trade name: Carbopol 941, BFGoodrich Chemical Company) Potassium hydroxide 0.2 Purification Water residue

Manufacturing method The oil phase part is melted 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. The emulsion obtained in this formulation example had an excellent whitening effect.

Example 17 (Emulsion) Microcrystalline wax 1.0 Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate ester 4.0 Polyoxyethylene (20 mol) Sorbitan mono Oleic acid ester 1.0 Propylene glycol 7.0 4-β-D-glucopyranosyloxysalicylic acid isobutyl ester 3.0 Ethyl paraben 0.3 Sodium hydrogen sulfite 0.01 Perfume proper amount Ion-exchanged water balance

Producing Method Propylene glycol is added to ion-exchanged water and heated to maintain it at 70 ° C. (aqueous phase). The other ingredients are mixed, dissolved by heating 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. The emulsion obtained in this formulation example had an excellent whitening effect.

Example 18 (Jelly) 95% Ethyl alcohol 10.0 Dipropylene glycol 15.0 Polyoxyethylene (50 mol) Oleyl alcohol ether 2.0 Carboxyvinyl polymer 1.0 (trade name: Carbopol 941, BF Goodrich Chemical Company) Caustic soda 0.15 L-Arginine 0.1 2-β-D-Glucopyranosyloxy-3-hydroxybenzoic acid eicosyl ester 0.05 Methylparaben 0.2 Ethylenediaminetetraacetate ・ 3 sodium ・ 2 water Japanese product 0.05 Perfume Appropriate amount Ion-exchanged water Residual

Preparation Method Carbopol 941 was uniformly dissolved in ion-exchanged water, while 2-β-D-glucopyranosyloxy-3-hydroxybenzoic acid eicosyl ester and polyoxyethylene (50 mol) were dissolved in 95% ethanol. The oleyl alcohol ether is dissolved and the Carbopol 941 aqueous solution is added.
Then, after adding other ingredients, caustic soda, L-
Neutralize with arginine and thicken. The jelly obtained in this formulation example had an excellent whitening effect.

Example 19 (Beauty liquid) (Phase A) Ethanol (95%) 10.0 Polyoxyethylene (20 mol) Octyldodecanol 1.0 Methylparaben 0.15 Pantothenyyl ether ether 0.1 3-β- D-Glucopyranosyloxysalicylic acid hexyl ester 0.05 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 ( Product name: Carbopol 941, BFGoodrich Chemical Company) Purified water Residual

Manufacturing 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.
The beauty essence obtained in this formulation example had an excellent whitening effect.

Example 20 (pack containing powder) (alcohol phase) 95% ethanol 10.0 propylene glycol 5.0 6-β-D-glucopyranosyloxysalicylic acid 2-hexadecyl ester 10.0 4-β- D-Glucopyranosyloxysalicylic acid propyl ester 1.0 Perfume proper amount Colorant proper amount (aqueous phase) Zinc white 25.0 Kaolin 20.0 Methylparaben 0.3 Glycerin 5.0 Ion-exchanged water Residual

Manufacturing method An aqueous phase is uniformly prepared at room temperature. Then, the alcohol phase prepared at room temperature is added and mixed uniformly. The pack obtained in this formulation example had an excellent whitening effect.

Example 21 (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 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid dodecyl ester 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water residual

Manufacturing method Soap powder and borax are added to ion-exchanged water and heated to maintain it 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 while stirring, and the reaction is carried out. 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. The cream obtained in this formulation example was excellent in whitening effect and also in rough skin improving effect.

Example 22 (Cream) Stearyl alcohol 4.0 Stearic acid 5.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 2-β-D-glucopyranosyloxy- 5-Hydroxybenzoic acid ethyl ester 20.0 Caustic potassium 0.2 Sodium bisulfite 0.01 Preservative proper amount Perfume proper amount Ion-exchanged water Residual

Producing method Propylene glycol and caustic potash are added to ion-exchanged water and heated 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 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, homogenize with a homomixer,
Cool to 30 ° C with good stirring. The cream obtained in this formulation example was excellent in whitening effect and also in rough skin improving effect.

Example 23 (Cream, Vitamin C Blend) Stearic Acid 6.0 Sorbitan Monostearate 2.0 Polyoxyethylene (20 mol) Hardened Castor Oil Ether 1.5 Propylene Glycol 10.0 2-β- D-Glucopyranosyloxy-5-hydroxybenzoic acid isopropyl ester 5.0 Glycerin trioctanoate 10.0 Squalene 5.0 Vitamin C 0.1 Sodium bisulfite 0.001 Ethylparaben 0.3 Perfume proper amount Ion Exchanged water residue

Manufacturing method Propylene glycol and vitamin C are added to ion-exchanged water and heated to maintain the temperature 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 to carry out preliminary emulsification, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring. The cream obtained in this formulation example had a whitening effect superior to that of the formulation containing no vitamin C.

Example 24 (Cream, Vitamin E Blend) Stearyl alcohol 7.0 Stearic acid 2.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) Cetyl Alcohol ether 3.0 Glycerine monostearate 2.0 Propylene glycol 5.0 2-β-D-Glucopyranosyloxy-5-hydroxybenzoic acid methyl ester 0.01 Vitamin E (dl-α-tocopherol) 0 .05 Fragrance Suitable amount Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Ion-exchanged water Residual

Producing Method Propylene glycol was added to ion-exchanged water, dissolved and heated to 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. The cream obtained in this formulation example was more excellent in whitening effect than that of the formulation not containing vitamin E.

Example 25 (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 2-β-D-Glucopyranosyloxy-5-hydroxy 2-pentyl ester 0.05 2-β-D-Glucopyranosyloxy-5-hydroxy 3-methyl- 1-Butyl ester 0.05 Perfume proper amount sodium bisulfite 0.03 ethylparaben 0.3 ion-exchanged water residual

Manufacturing method Soap powder and borax are added to ion-exchanged water and heated to maintain it 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 while stirring, and the reaction is carried out. 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. The cream obtained in this formulation example was excellent in whitening effect and also in rough skin improving effect.

Example 26 (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 Triethanol Amine 1.0 2-β-D-Glucopyranosyloxy-5-hydroxybenzoic acid dodecyl ester 0.001 Sodium hydrogen sulfite 0.01 Ethylparaben 0.3 Carboxyvinyl polymer 0.05 (trade name: Carbopol 941 , BFGoodrich Chemical Company) Fragrance, appropriate amount, ion-exchanged water, residual

Manufacturing 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 uniformly emulsified with a homomixer. After emulsification, the mixture is cooled to 30 ° C. with thorough stirring. The emulsion obtained in this formulation example was excellent in whitening effect and also in rough skin improving effect.

Example 27 (Emulsion, UV absorber blend) (Oil phase part) Stearyl alcohol 1.5 Squalane 2.0 Vaseline 2.5 Deodorant liquid lanolin 1.5 Evening primrose oil 2.0 Isopropyl myristate 5.0 Glycerin monooleate 2.0 Polyoxyethylene (60 mol) hydrogenated castor oil 2.0 Tocopherol acetate 0.05 Ethylparaben 0.2 Butylparaben 0.1 2-β-D-Glucopyranosyloxy-5-hydroxy 3-Methyl-3-pentyl ester 1.0 Para-aminobenzoic acid 0.1 Perfume proper amount (aqueous phase part) sodium bisulfite 0.001 glycerin 5.0 sodium hyaluronate 0.01 carboxyvinyl polymer 0.02 (trade name) : Carbopol 941, BFGoodrich Chemical Company) Potassium hydroxide 0.2 Ltd. water Balance

Manufacturing method The oil phase part is melted 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. The emulsion obtained in this formulation example was excellent in whitening effect and also in rough skin improving effect.

Example 28 (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-β-D-glucopyranosyloxy-5-hydroxy 2,6-dimethyl-4-heptyl ester 3.0 Ethylparaben 0.3 Sodium hydrogen sulfite 0.01 Fragrance Suitable amount Ion exchange water Residual

Producing method Propylene glycol is added to ion-exchanged water and heated to maintain it at 70 ° C (aqueous phase). The other ingredients are mixed, dissolved by heating 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. The emulsion obtained in this formulation example was excellent in whitening effect and also in rough skin improving effect.

Example 29 (Jelly) 95% Ethyl alcohol 10.0 Dipropylene glycol 15.0 Polyoxyethylene (50 mol) Oleyl alcohol ether 2.0 Carboxyvinyl polymer 1.0 (trade name: Carbopol 941, BF Goodrich Chemical Company) Caustic soda 0.15 L-arginine 0.1 2-β-D-glucopyranosyloxy-5-hydroxy eicosyl ester 0.05 Methylparaben 0.2 Ethylenediaminetetraacetate ・ 3 sodium dihydrate 0.05 Fragrance Suitable amount Ion-exchanged water Residual

Manufacturing method Carbopol 941 was uniformly dissolved in ion-exchanged water, while 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid eicosyl ester and polyoxyethylene (50 mol) were dissolved in 95% ethanol. The oleyl alcohol ether is dissolved and the Carbopol 941 aqueous solution is added.
Then, after adding other ingredients, caustic soda, L-
Neutralize with arginine and thicken. The jelly obtained in this formulation example had an excellent whitening effect.

Example 30 (Beauty Solution) (Phase A) Ethanol (95%) 10.0 Polyoxyethylene (20 mol) Octyldodecanol 1.0 Methylparaben 0.15 Pantothenyylether 0.12-β- D-Glucopyranosyloxy-5-hydroxyhexyl ester 0.05 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0 2 (Brand name: Carbopol 941, BFGoodrich Chemical Company) Purified water Residue

Manufacturing 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.
The beauty essence obtained in this formulation example was excellent in whitening effect and also in rough skin improving effect.

Example 31 (pack containing powder) (alcohol phase) 95% ethanol 10.0 propylene glycol 5.0 2-β-D-glucopyranosyloxy-5-hydroxy 2-hexadecyl ester 10.0 2 -Β-D-Glucopyranosyloxy-5-hydroxy isopropyl ester 1.0 Perfume Appropriate amount Coloring agent Appropriate amount (aqueous phase) Zinc white 25.0 Kaolin 20.0 Methylparaben 0.3 Glycerin 5.0 Ion-exchanged water Remnant

Manufacturing method An aqueous phase is uniformly prepared at room temperature. Then, the alcohol phase prepared at room temperature is added and mixed uniformly. The packs obtained in this formulation example were excellent in whitening effect and also in rough skin improving effect.

Example 32 (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 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid benzyl ester 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water residual

Manufacturing method Soap powder and borax are added to ion-exchanged water and heated to maintain it 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 while stirring, and the reaction is carried out. 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. The cream obtained in this formulation example was excellent in whitening effect and also in rough skin improving effect.

Example 33 (Emulsion) (Oil Phase Part) Stearyl alcohol 1.5 Squalane 2.0 Vaseline 2.5 Deodorizing liquid lanolin 1.5 Evening primrose oil 2.0 Isopropyl myristate 5.0 Glycerin monooleate 2. 0 polyoxyethylene (60 mol) hydrogenated castor oil 2.0 tocopherol acetate 0.05 ethylparaben 0.2 butylparaben 0.1 4-β-D-glucopyranosyloxysalicylic acid methyl ester 1.0 paraaminobenzoic acid 0 1 Fragrance Suitable amount (water phase part) Sodium hydrogen sulfite 0.001 Glycerin 5.0 Sodium hyaluronate 0.01 Carboxyvinyl polymer 0.02 (trade name: Carbopol 941, BFGoodrich Chemical Company) Potassium hydroxide 0.1. 2 Purified water Residual

Manufacturing method The oil phase part is melted 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. The emulsion obtained in this formulation example had an excellent whitening effect. The safety and stability were also good.

[0072]

As described above, since the glycoside of hydroxysalicylic acid or the glycoside of hydroxysalicylic acid ester according to the present invention has a whitening effect superior to that of the conventional one, it is expected to be used in a small amount. It is a safe compound that can exert effects. Further, among the glycosides according to the present invention, the gentisic acid ester glycoside also has a rough skin improving effect. Therefore, it is possible to provide a highly safe external preparation for skin having an excellent whitening effect and / or a rough skin improving effect by incorporating the compound.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical indication location // C07H 15/203 (72) Inventor Yuki Shibata 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Stock Ceremony Company Shiseido Daiichi Research Center (72) Inventor Rumiko Kaku 1050 Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa Stock Company Shiseido Daiichi Research Center

Claims (1)

[Claims] 1. A skin external preparation containing at least one glycoside of hydroxysalicylic acid and / or a glycoside of hydroxysalicylic acid aliphatic ester represented by the general formula 1. [Chemical 1] (In the formula, R ₁ represents hydrogen or a saturated hydrocarbon group having 1 to 20 carbon atoms or an unsaturated hydrocarbon group, which hydrocarbon group may be linear or branched. One of R _{2 and} R ₃ Is a sugar residue and the other represents hydrogen.)