JP3120087B2 - Hair cosmetics for prevention of gray hair and blackening of gray hair - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to catechol-O-β-D
-Hair cosmetics for preventing and blackening white hair, comprising galactoside or resorcinol-O-β-D-galactoside as an active ingredient (including quasi-drug cosmeceuticals and medicinal cosmeceuticals). The same applies hereinafter).

[0002]

2. Description of the Related Art Whitening of human hair has been recognized as a typical phenomenon in the physiological aging process. Also, albinism is a clinically common skin disorder, such as vitiligo vulgaris, albinism,
It is known as a symptom such as alopecia areata, but in some cases, treatment of the primary disease can prevent the occurrence of white hair. In addition, whitening due to nutritional disorders and chronic systemic diseases has been reported.

[0003] At present, there is no fundamental pharmacotherapy for whitening as a physiological aging phenomenon, and graying with a hair dye (hair dye) is only performed as a cosmetic means. The use of hair dyes is a passive means of simply hiding gray hair, and its effects are temporary, often accompanied by hair damage, and there are many cases of allergic contact dermatitis There are difficulties such as.

Also, melanocyte stimulating hormone (TKSa)
It is said that hormonal substances such as wyer, et al., Amer. Zool., 23, 529 (1986)) and β-lipotrophin (JP-A-1-207226) have an effect of preventing the development of white hair, but hormones are used systemically. It is not suitable for hair cosmetics that are widely and safely used.

[0005]

DISCLOSURE OF THE INVENTION The present invention, despite the great social demands, has no fundamental treatment or preventive means and, at present, does not develop useful drugs. An object of the present invention is to provide a novel hair cosmetic that has a preventive effect on whitening and a blackening effect of white hair, and can be used safely.

[0006]

Means for Solving the Problems The gist of the present invention is that catechol-O-β-D-galactoside or resorcinol-O-β-D-galactoside is contained as an active ingredient. And a hair cosmetic for preventing gray hair and blackening white hair.

Catechol (1,2-Benzenediol) and resorcinol (1,3-Benzenediol) are isomers of hydroquinone (1,4-Benzenediol). Hydroquinone is widely used in foreign countries and in Japan by some dermatologists as a skin bleaching agent. However, hydroquinone has problems in safety such as primary skin irritation and sensitization, and has not been widely used in general.

In recent years, a number of studies have been conducted on hydroquinone derivatives for the purpose of reducing side effects while maintaining the effects of hydroquinone.
It is known that O-β-D-glucopyranoside (arbutin) exerts a remarkable skin whitening effect by suppressing the activity of the oxidase tyrosinase that produces melanin pigment (Japanese Patent Application Laid-Open No. 60-56912). Gazette.).

[0009] However, the present inventors have surprisingly found that
By combining catechol or resorcinol, which is an isomer of hydroquinone, with galactose by an enzyme that transfers galactose to polyphenol, the β-glycoside obtained purely has the opposite property to the hydroquinone glycoside, that is, melanin. It has been found that it has the property of promoting the activity of the oxidase tyrosinase that produces the pigment.

Regarding the mechanism of gray hair development, Fitzpatrick
They show changes in the pigment cell line (Fitzpatri
ck T.In "Advance in Biology of Skin" Pergamon Press
P35.1965), that is, the decrease or disappearance of the activity of tyrosine oxidase (tyrosinase) in the pigment cells of the hair matrix contributes to gray hair.

[0011] By applying a hair cosmetic containing catechol-O-β-D-galactoside or resorcinol-O-β-D-galactoside as an active ingredient to the skin, oxidase tyrosinase, which is greatly involved in melanin formation in hair, is applied. It increases the activity, promotes the enhancement of melanin pigment, and is effective in preventing whitening and blackening of hair.

The amount of catechol-O-β-D-galactoside or resorcinol-O-β-D-galactoside depends on the dosage form and is not particularly limited, but is usually 0.0001 to 30% by weight. , Preferably 0.
When the amount is less than 0.0001% by weight, it is difficult to obtain a sufficient effect of preventing whitening and blackening of the hair. An increase in the blackening effect cannot be expected.

The hair cosmetic composition of the present invention comprises a hair tonic,
Hair treatments, hair creams, hair shampoos, hair rinses can be any externally applicable dosage form, and the components thereof are various components commonly used in cosmetics, quasi-drugs, pharmaceuticals, and the like, such as alcohol. Solvents and dissolution aids, surfactants, humectants, fragrances, coloring agents, preservatives, viscosity modifiers, and the like can be appropriately compounded.

[0014]

The results of the hair cosmetic of the present invention thus obtained with respect to efficacy and safety are as follows.

Synthesis of catechol-O-β-D-galactoside or resorcinol-O-β-D-galactoside is an enzyme that degrades a substrate such as β-galactoside and transfers galactose to polyphenol, ie, lactase, β-galactoside. It can be performed using galactosidase, β-galactanase and the like. For example, lactase or β
-When using galactosidase, lactose as a substrate,
When β-galactanase is used, arabinogalactan is used.

[Test Example] Test Example 1: Synthesis of catechol-O-β-D-galactoside. 50 ml of a reaction mixture consisting of 2.5% (w / v) catechol, 5% (w / v) lactose, 10 mM phosphate buffer (pH 6.0) and 1 unit / ml lactase (from Bacillus circulans)
Was placed in an Erlenmeyer flask (200 ml), the reaction was carried out at 40 ° C. for 20 hours, the reaction was stopped by adding 100 ml of ethanol to the reaction mixture, and the insoluble precipitate was removed by centrifugation. After the residue was subjected to vacuum concentration and drying treatment, the residue was dissolved in water (10 ml), the aqueous solution was subjected to column chromatography under the following conditions, and the reaction product was eluted with an eluent volume of 480 to 540 ml. Column: 2.6 cm × 91 cm in inner diameter Filler: Biogel P-2 (400 mesh) Eluent: 5% (v / v) aqueous ethanol solution The obtained fraction was concentrated to dryness under reduced pressure, and further dried in a vacuum dryer The product was dried using to obtain 32 mg of the product as a white powder. The product was single in thin layer chromatography under the following conditions (Rf value: 0.6
0): Thin layer: Silica gel 60F254 Developing solvent: Ethyl acetate / acetic acid / water (3: 1: 1) Detection: UV irradiation or spraying of a sulfuric acid / methanol (1: 2) mixture, followed by heating to 110 to 120 ° C. Let it develop color. The molecular structure of the product (catechol-O-β-D-galactoside) was confirmed by ¹ H-NMR and ¹³ C-NMR.

Test Example 2: Resorcinol-O-β-D
-Synthesis of galactoside. The same operation was performed using resorcinol instead of catechol of Test Example 1, and the product was converted to a white powder by 30 m
g was obtained. The product was single in thin layer chromatography under the following conditions (Rf value: 0.62): Thin layer: silica gel 60F254 Developing solvent: ethyl acetate / acetic acid / water (3: 1: 1) : UV irradiation or spraying of a sulfuric acid / methanol (1: 2) mixture, followed by heating to 110 to 120 ° C. to develop color. The molecular structure of the product (resorcinol-O-β-D-galactoside) was confirmed by ¹ H-NMR and ¹³ C-NMR.

Test Example 3: Activity promoting activity of tyrosinase Catechol-O-β-D-galactoside obtained in Test Example 1 and resorcinol-O- obtained in Test Example 2
The melanin-producing effect of β-D-galactoside was evaluated by the following method. As an index of the hair whitening prevention effect, a method represented by a ratio that promotes the activity of an oxidase tyrosinase that produces a melanin pigment was used. Promotion of tyrosinase activity: Promotion of tyrosinase activity
L-Dopa was used as a substrate in the following separate procedure. Accelerator solution: Various concentrations of aqueous solutions of catechol-O-β-D-galactoside or resorcinol-O-β-D-galactoside were prepared. Enzyme solution: Tyrosinase (Sigma) 2000 units /
It was prepared by dissolving in water to make the volume of the solution. Measurement: Add 0.5 ml of substrate solution and 0.9 ml of phosphate buffer (20 mM: pH 6.5) to 0.05 ml of sample,
Incubate at 5 ° C for 5 minutes. To this was added 0.05 ml of the enzyme solution previously incubated at 25 ° C., and 1.5
The mixture was allowed to react for minutes, and the absorbance at 475 nm was measured. The activity promotion rate was calculated by the following equation.

(Equation 1) T: Absorbance when accelerator is added T ': Absorbance when accelerator is added and no substrate is added C: Absorbance when accelerator is not added C': Absorbance when neither accelerator nor substrate is added The results obtained are as follows. The results are shown in Table 1. As a result, catechol-O-β-D-galactoside and resorcinol-O-β-D-galactoside, which are the active ingredients of the hair cosmetic composition of the present invention, show that the activity of tyrosinase to form a melanin pigment. Can be said to be effective in preventing hair whitening and blackening.

[Table 1]

Test Example 4: Culture pigment cell blackening test 1.5 × 10 ⁶ B-16 mouse melanoma cells were spread on a dish containing 4 ml of Eagle's medium (containing 10% fetal bovine serum), and catechol-O-β was added. -D-galactoside or resorcinol-O-β-D-galactoside (0.1, 10 and 10 μg / ml medium) at 37 ° C., 5%
The cells were cultured for 3 days in a CO ₂ incubator kept at CO ₂ .
The cultured cells were dissociated with trypsin and dispersed, and then the number of cells was counted. In addition, PTCA (pyrrole-2,3,5-tricar) produced by oxidatively decomposing the amount of eumelanin in cells with permanganic acid.
boxylic acid) was measured by high performance liquid chromatography. The results are shown in Tables 2 and 3, from which catechol-O-β-, which is an active ingredient of the hair cosmetic of the present invention, was obtained.
D-galactoside and resorcinol-O-β-D-galactoside promote the production of melanin pigment without affecting the growth of cultured pigment cells, and can be effective in preventing whitening and blackening of hair. It became clear.

[Table 2]

[Table 3]

Test Example 5: Patch Test Sample: 10% aqueous solution of catechol-O-β-D-galactoside or resorcinol-O-β-D-galactoside Method: 20 males and females up to 20 to 60 years old
A filter paper for a fin chamber in which a sample and a control solution (physiological saline) were immersed, respectively, was put into the chamber part of the fin chamber on the upper arm flexion side of a total of 40 subjects, and this was affixed. Carried out. The application time was 24 hours, the fin chamber was removed after 24 hours, and 30 minutes and 24 hours after removing the sample.
The judgment was performed three times for eight hours. Judgment criteria:-: No reaction ±: Slight erythema +: Obvious erythema ++: Erythema and swelling or papule +++: Blisters observed As shown in Table 4, catechol -O as an active ingredient of the hair cosmetic of the present invention It was revealed that -β-D-galactoside and resorcinol-O-β-D-galactoside have a very low possibility of inducing a stimulating reaction and an allergic reaction and are highly safe.

[Table 4]

[0021]

Examples of the present invention will be described below. Note that the following examples do not limit the present invention at all. Example 1 <Heart tonic> Catechol-O-β-D-galactoside 0.5 g Polyoxyethylene (9) lauryl ether 1.0 g 1,3 butylene glycol 5.0 g Ethanol 50.0 g Fragrance 0.3 g Purified water qs ────────────────────────────────── Total amount 100.0g

Example 2 <Heart treatment> Resorcinol-O-β-D-galactoside 1.0 g Polyoxyethylene (10) behenyl ether 5.0 g Glycerin monostearate 6.0 g Isopropyl myristate 5.0 g Stearic acid 5.0 0 g Liquid paraffin 5.0 g Lanolin alcohol 3.0 g 1,3 butylene glycol 5.0 g Triethanolamine 1.0 g Methyl paraben 0.1 g Ethyl paraben 0.1 g Fragrance 0.3 g Purified water qs ────────────────────────── Total amount 100.0g

Example 3 <Hair cream> Catechol-O-β-D-galactoside 1.0 g Liquid paraffin 30.0 g Dehydrated lanolin 3.0 g Beeswax 2.0 g Cetanol 3.0 g Glycerin 5.0 g Polyoxyethylene (10) Cetyl ether 3.0 g Sorbitan monostearate 0.1 g Methyl paraben 0.1 g Ethyl paraben 0.1 g Fragrance 0.5 g Purified water qs ───────────── Total amount 100.0g

Example 4 <Hair Shampoo> Resorcinol-O-β-D-galactoside 0.5 g Triethanolamine lauryl sulfate 20.0 g Sodium lauryl sulfate 5.0 g Magnesium stearate 5.0 g Lanolin 1.0 g 1,3 butylene Glycol 5.0 g Cetyl alcohol 2.0 g Polyvinyl alcohol 1.0 g Flavor 0.5 g Purified water qs ───────────────────────────── ────── Total amount 100.0g

Example 5 <Hair rinse> Catechol-O-β-D-galactoside 0.5 g Polyoxyethylene (2) oleyl ether 7.0 g Distearyldimethylammonium chloride 3.0 g Propylene glycol 3.0 g Methyl paraben 0.1 g Ethyl paraben 0.1 g Perfume 0.3 g Purified water suitable amount ─────────────────────────────────── total amount 100. 0g

[0026]

According to the present invention, there is provided a hair cosmetic comprising catechol-O-β-D-galactoside or resorcinol-O-β-D-galactoside as an active ingredient, which has the above-mentioned action. Therefore, it has a preventive effect on whitening of hair due to aging and the like, is also effective for blackening of gray hair, is extremely safe, and is expected to have sufficient practical application, and It has great significance.

Continuation of front page (72) Inventor Yoshikatsu Sayama 2-9-1 Kyobashi, Chuo-ku, Tokyo Chugai Pharmaceutical Co., Ltd. (58) Field surveyed (Int. Cl. ⁷ , DB name) A61K 7 / C07H 15 / CA (STN)

Claims (2)

(57) [Claims] 1. A hair cosmetic for preventing gray hair and blackening white hair, comprising catechol-O-β-D-galactoside as an active ingredient. 2. A hair cosmetic for preventing gray hair and blackening white hair, comprising resorcinol-O-β-D-galactoside as an active ingredient.