JPS6127909A - External drug for skin - Google Patents

Abstract

PURPOSE:To provide an external drug for the skin, containing a specific 2,3- dimethoxy-5-methyl-1,4-benzenediol derivative, and having remarkably improved skin-beautifying effect and high safety. CONSTITUTION:The compound of formula I or formula II, e.g. 2,3-dimethoxy-5- methyl-6-decaprenyl-1,4-benzenediol, 2,3-dimethoxy-5-methyl-6-(3', 7', 11', 15', 19', 23',27'-heptamethyl-octacosyl)-1,4-benzenediol, etc. is used as a component of the objective drug. The amount of the compound in the drug is 0.0001-10wt%, preferably 0.01-5wt%. The external drug has no stimulation and little sensitizing effect, and can be used continuously for a long period or at a high concentration. The skin-beautifying effect of the drug can be fully demonstrated thereby.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a skin external preparation, and more particularly to a highly safe skin external preparation with significantly improved whitening effects.

Although there are some unknown points regarding the mechanism of occurrence of skin spots, it is generally thought that melanin pigment is formed due to hormonal abnormalities or stimulation from ultraviolet rays, and this is abnormally deposited in the skin. It is being

Treatments for such bruises include the administration of large doses of substances that inhibit melanin production, such as vitamin C, glutathione, and cysteine, injections, or topical administration in the form of ointments, creams, and lotions. Methods such as coating are used. Furthermore, in Europe and America, Hyde l:J quinone preparations are used as pharmaceuticals. However, vitamin C has problems in terms of stability.
Particularly in systems containing water, it is unstable and may cause discoloration or discoloration5! , and thiol compounds such as glutathione and cysteine have a strong odor and are easily oxidized, so their inclusion in cosmetics is avoided.

Furthermore, these compounds do not have a sufficient whitening effect because their effects are extremely slow to appear when hydroquinone is added. On the other hand, although the effect of hytroquinone has been recognized to some extent, its use is generally restricted because it has strong sensitizing properties.

In view of these circumstances, the present inventors have carried out extensive research and have found that the compound of the general formula (I) or (II>) has excellent skin safety, and also has good stability.
Furthermore, it was discovered that the whitening effect is almost the same as that of hehydroquinone, leading to the completion of the present invention.

That is, the present invention is an external skin preparation characterized by containing one or more compounds selected from the group consisting of compounds represented by the following general formulas (T) and (n).

1 formula (T), (n), n = 1 to 10] (below margin) The configuration of the present invention will be described below.

Examples of the compound of general formula (I) used in the present invention include 2.3-dimethoxy-5-methyl-6-prenyl-1
, 4-penzenediol (n=1), 23-dimethoxy-5-methyl-6-diprenyl-1,4-penzenediol (n=2), 2,3-dimethoxy-5-methyl-
6-hebutaprenyl-L4--benzenediol (n=
7), 2.3=dimethoxy-5-methyl-6-zocaprenyl-14-henzenediol (n-10), etc., and examples of the compound of general formula (II) include 2,3-dimethoxy -5-methyl-〇-(3',
7', 11'+15', 19"+23'+27'+-heptanotyl-offucosyl)-1,4-henzenediol (n=7), 2,3-dimethoxy-5-methyl-6-
(3', 7', 11', 15', 19', 23', 27
', 31', -occumethyldotriacontyl)1.
4-penzenediol (n=8), 2,3-dimethoxy-5-methyl-6-(3°, 7', 11', 15',
19', 23', 27', 31', 35', 39-decamethylta-1 lacontyl)-14-henzenediol (
For example, n=”io).

In the present invention, any one or more selected from the above may be used.

The blending amount is generally 0.0001 to 10% by weight, preferably 0.01 to 5% by weight.

Next, the results of testing the whitening fruit of the present invention will be explained. [Skin Whitening] As an indicator of the fruit, a method was used in which the rate of inhibition of tyrosinase, an oxidative enzyme for melanin production, which is commonly used, was used.

Tyrosinase Inhibition Tyrosinase inhibition rate was determined using DOPA as a substrate using the following procedure.

Sample solution 2. 12 tng of 3-ditoxy-5-methyl-6-zocabreny-1,4-henzenediol was added to 10 ml of acetone.
Melt to 1.

Dissolve 5 m of substrate solution Dopa in 1 g of phosphorus M buffer (I/1\r, pl+6.8) IQml.

Enzyme 1 (ζ Dirosinase (2000 units, / mg, Sigma)
10 mg of phosphoric acid (]/15 mol, p
l! 6.8) Dissolve to make 10ml.

Add 0.05 n+l of enzyme solution and 0.45 ml of phosphate buffer solution to 0.5 ml of the measurement sample, and incubate at 25°C for 5 minutes. To this, 0.5 ml of an enzyme solution incubated at 25° C. was added, reacted for 1.5 minutes, and the absorbance at 475 nm was measured.

The inhibition rate was calculated by the following formula, and 2,3-dimethoxy-5
The inhibition rate of -methyl-6-zocaprenyl-1,4-henzenediol was 55.1% (C degree 0.06%).

T-T' Inhibition rate - (i --------1--> x 1o o
<%) c-c' T: Absorbance when inhibitor is added T': Absorbance when inhibitor is added and no substrate is added C: Absorbance when no inhibitor is added C': Inhibitor As is clear from the absorbance scattering when neither substrate nor substrate is added, 2,3-dino-1-xy-5-methyl-6-zocaprenyl 1. ．． It can be seen that 4-henzenediol has a good inhibitory effect on thyroxinase activity.

The external skin preparation of the present invention can be in the form of cream, lotion, emulsion, puncture, soap, ointment, and the like.

Skin J7 of the present invention: In addition to the above-mentioned essential ingredients, if necessary, within a quantitative and qualitative range that does not impair the effects of the present invention, the skin preparation may contain a moisturizing agent, a surfactant, and a pigment. , fragrances, preservatives,
Antioxidants, cleaning agents, skin IW nutrients, hair nutrients, enzymes, etc. are blended. Examples of skin layer nutrients, hair care agents, and enzymes include iodotyrosine and its derivatives,
Amino acids such as methionine and its derivatives, lysine, serine, glycocol and their derivatives, pantothenic acid, biotin, vitamin I32, Hikumin BL+, 2.
Examples include vitamins such as dinic acid, vitamin D, and vitamin F, female hormones, brain TTi body bolmon, enzymes and hormones such as the enzyme phosphorylase, and other substances such as inositol, orotic acid, thioctic acid, and chondroitin sulfate.

Furthermore, it is effective to add an ultraviolet absorber to prevent stains, freckles, etc.

Examples of ultraviolet absorbers include para-aminobenzoic acid ethyl ester, para-dinotylaminobenzoic acid ethyl ester, cynoxa-1~, para-7' toxo+I skin U (i ethylhegysyl ester, 2.2'-4 ,4'-
Examples include -tetrahydroxyhensiphenone, sulfonic acid salts of 2-droxy-.1-me-I-xyhensiphenone or (85L-245), and silicanic acid.

The skin and nail external preparation of the present invention is non-irritating and has almost no sensitization, so it can be used continuously for a long period of time and in high concentrations, and can fully exhibit its skin whitening effect.

The present invention will be explained in more detail by referring to examples. The present invention is not limited thereby. Combination■
is weight %.

[Actual M+i example 1] Honey cream stearic acid
5.0 Stearyl alcohol 4.0 Stearic acid butyl alcohol ester 8.0 Glycerin monostearic acid ester 2.0 Copylene gelicol
10.02.3-Jitquin-5-nonal-6-decaprenyl-1,4-henzenediol
4.0 caustic potash
0.2 Preservatives/antioxidants
Appropriate amount of fragrance Appropriate amount of ion-exchanged water Remainder (manufacturing method) Add propylene glycol and caustic potassium to ion-exchanged water, dissolve, heat, and keep at 70°C (water phase).

Mix other ingredients and heat and keep at 70°C (oil phase).

Gradually add the oil phase to the aqueous phase, and once all has been added, keep at that temperature for a while to allow the reaction to occur. Then, use a rice mixer to uniformly emulsify the mixture, and cool to 30°C while stirring well.

(Left below) U Example 2 Neutral cream Stearyl alcohol 7.0 Stearic acid 2.0 Squalane 5,0 Hydrogenated lanolin 2.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) Cetyl alcohol ether
3. Q Glycerin Monostearate Conistere 2.0 Propylene Glycol
5.02.3-dimethoxy-5-methyl-6-(3
',7'.

11', 15', 19', 23', 27°-hebutamethyl-6occucosyl)-1,4-henzenediol 1
．． 52.3-dimethoxy-5-methyl-6-hebutaprenyl-L4-penzenediol 1.5 Fragrance
Appropriate amount of preservatives and antioxidants Appropriate amount of ion exchange water
Residue (manufacturing method) Add propylene glycol to ion-exchanged water and keep at 70°C for 4 hours (water phase). Mix other ingredients, heat and melt and keep at 70°C (oil phase). Add the oil phase to the aqueous phase, homogeneously emulsify the pre-emulsification using a homomixer, and after emulsification stir while cooling.

(Left below) [Example 3 Coco Cold Cream Solid paraffin 4.0 Beeswax 8.0 Vaseline 12.0 Liquid paraffin 35.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) Sorbicun monolaurate 2 .0 soap powder
0.1 bow sand
0.22.3-dimethoxy-5
-Methyl-6-(3', 7'.

11'+15', 19', 23'+27'+31', 3
5'-nonamethyl-quizatriacontyl) -L4
-Henzenediol 10.0
Ion exchange water Residual fragrance
Appropriate amount Preservative/Antioxidant Appropriate amount (manufacturing method) Add soap powder and borax to ion-exchanged water, heat and dissolve, and maintain at 70"C (water phase). Mix other ingredients, heat and melt, and maintain at 70°C. Keep (oil phase). Gradually add the oil phase to the aqueous phase while stirring and react. After the reaction is complete, emulsify uniformly with a homomixer, and after emulsification, stir well and cool to 30°C.

[Example 4] Emulsion Stearic acid 2.5 Cetyl alcohol 2.0 Vaseline 5.0 Liquid paraffin 10.0 Polyethylene (I0 mol) Monooleic acid ester 2.0 Polyethylene glycol 1500 3.01-
Reethanolamine 1,02.
3-dimethoxy-5-methyl-6-zocaprenyl 1,
4-henzenediol 1.0 ion exchange water residual fragrance
Appropriate amount of preservatives and antioxidants
Appropriate amount (manufacturing method) Polyethylene glycol in ion exchange water!・Add reethanolamine, dissolve by heating, and keep at 70°C (aqueous phase).

Mix other ingredients, heat and dissolve and maintain at 70°C (oil phase). The oil phase is pre-emulsified by adding the oil phase to the water phase, and the mixture is uniformly emulsified using a homomixer. After emulsification, the mixture is cooled to 30°C while stirring.

(Left below) [Example 5] Lotion (alcohol phase) 95% ethanol 21.0
Polyoxyethylene (60 moles) Hardened mustard oil ether 1.4 Preservatives/antioxidants Appropriate amount Fragrance
■2.3-diphthoquine-5-methyl-6-(3", 7'.

11', 15', 19', 23', 27', 31', 3
5', 39'-decanothylute 1 lacontyl) -1,
4-henzenediol 0.1
(Aqueous phase) Glycerin 5.0 Sodium 2-hydroxy-4-methoxyhensiphenone-5-sulfonate 0.3 Sodium hexaclate 3! I [i ion exchange water
Residue (method g) After adjusting the aqueous phase and alcohol phase, solubilize.

[Example 6] Jelly 95% conitanol 10
．． O dipropylene glycol 15.
0 Polyoxyethylene (I5 mol) Oleyl alcohol ether 2.0 Carboxy vinyl polymer 1.0 (Product name: Carbodogol 941) Caustic potash 0.15
L-arginine 0.12.
3-dino I xy-5-rmethyl-6-diprenyl-1
,4-penzenediol 0.01 urocanic acid 0.1 fragrance
Appropriate amount of preservative
Appropriate amount of ion exchange water
Residue (manufacturing method) Carboball 941 was uniformly dissolved in ion-exchanged water, while dipropylene glycol, polyoxyethylene (I 5 mol) oleyl alcohol ether, 2,3-dimethoxy-5-methylene 6 tecabreni were dissolved in 95% ethanol. C1. +i-henzenediol and other ingredients are melted and added to the aqueous phase. Then, it is neutralized and thickened with caustic potassium and L-arginine.

[Example 7] Water-absorbing soft vaseline 40.0
Stearyl alniole 13.0
Mokuro 15.0 Polyoxyethylene (I0 mol) Monooleic acid ester 0.25 Glycerin monostearic acid ester 0,252.
3-dimethoxy-5-nonal-6-prenyl-114-
Henzenediol 10.0 Ion-exchanged water Residual (manufacturing method) Keep ion-exchanged water at 70°C (aqueous phase). 7
Mix and dissolve at 0°C (oil phase). Add the oil phase to the water phase, homogeneously emulsify with a bomomi grinder, and then cool.

All of the external skin preparations of Examples 1 to 7 had excellent whitening effects such as lightening sunburned skin, had little skin irritation and sensitization, and had excellent stability over time.

Claims (1)

[Scope of Claims] An external skin preparation characterized by containing one or more compounds selected from the group consisting of compounds represented by the following general formulas (I) and (II). ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In formulas (I) and (II), n = 1 to 10]