JPH10182400A - Cosmetic - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a cosmetic having melanogenesis suppressing action and depigmentation action and effective for the prevention, improvement, etc., of spots, freckles and dark skin caused by sunburn, etc. SOLUTION: The objective cosmetic is produced by compounding (A) 0.1-5wt.%, preferably 0.25-2wt.% of phenylhydroquinone of the formula with (B) constituent components for the preparation of various cosmetics such as melanogenesis suppressing agent, ultraviolet absorber, ultraviolet scattering agent, antiinflammatory agent, vitamins, steroid agent, antioxidant (e.g. ascorbic acid), agent for acidifying the base of preparation (e.g. sodium bisulfite), etc. The cosmetic may be formed in the form of cream, milky lotion, pack, face wash, etc. Other names of phenylhydroquinone are phenylhydroquinol, 2,5- hihydroxybiphenyl, 1,1'-(biphenyl)-2,5-diol, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a cosmetic containing phenylhydroquinone as an active ingredient. INDUSTRIAL APPLICABILITY The cosmetic of the present invention is effective for preventing and improving the occurrence of spots, freckles, and dark spots due to sunburn and the like, and for whitening skin, due to its melanin production inhibitory action and depigmenting action.

[0002]

2. Description of the Related Art Pigmentation of human skin represented by spots and freckles ranges from pathological to aging and ultraviolet rays, and the causes thereof are various. Development of therapeutic agents for pigmentation disorders and whitening cosmetics that control these is one of the important issues in the fields of pharmaceuticals and cosmetics. For the purpose of controlling pigmentation, hitherto ascorbic acid derivatives or complex compounds thereof (for example, JP-A-63-198674), kojic acid (JP-A-63-2770619), hydroquinone and its derivatives (arbutin: 16906), linoleic acid (JP-A-64-8
5907), and plant components (JP-A-1-149706) and animal components (JP-A-1-43887). Hydroquinone has been approved by the FDA in the US for its safety and efficacy as an over-the-counter (OTC) drug (Federal Regist
er, 47, 39108, 1982), and are sold in general pharmacies. However, in Japan, it is used only in some clinical settings in terms of primary skin irritation and sensitization, but its effectiveness is evaluated by dermatologists.

[0003] Phenylhydroquino
ne), also known as 2,5-dihydroxybiphenyl (2,5-dihydrox
Ybiphenyl) is a compound in which a phenyl group is bonded to the 2-position in terms of the chemical structure of hydroquinone. Ortho-phenylphenol, in which the 5-position hydroxyl group of the two hydroxyl groups of phenylhydroquinone is removed,
Also known as 2-hydroxybiphenyl
Is currently designated as a food additive in Japan as a fungicide for citrus fruits, and is also used as a preservative and fungicide for cosmetics. Ito et al. (Bull. Pharm. Res. Inst.,
76, 5-13, 1968) and Kahn (Arch.Dermatol., 102,
177-187, 1970). However, it has not been known that phenylhydroquinone has a skin whitening effect or a melanin suppressing effect.

[0004]

The object of the present invention is that any of the above-listed conventional treatments for pigmentation and whitening cosmetics are insufficient in their effect, and are not effective for spots, freckles, and blacks due to sunburn. In view of the fact that interest in prevention and improvement of skin lightening and skin whitening has increased, it is an object of the present invention to provide a more effective cosmetic.

[0005]

The present inventors have continued to search for a substance having a whitening effect capable of solving the above-mentioned problems, and as a result, have found that phenylhydroquinone is a compound having a remarkable whitening effect. They have discovered and completed the present invention. That is, the present invention is a cosmetic containing phenylhydroquinone as an active ingredient.

The action of the cosmetic of the present invention is to prevent the occurrence of spots, freckles and darkening by suppressing the production of melanin, and to depigment the generated stains, freckles and darkening to whiten it. . Hereinafter, the present invention will be described in detail.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Phenylhydroquinone (phenylhydroquinone: phen) is an active ingredient of the cosmetic of the present invention.
ylhydroquinone) is another name for phenylhydroquinol, 2,5-dihydroxybiphenyl, 2,5-dihydroxydiphenyl, 1,1 '-(biphenyl)-
2,5-diol [1,1 '-(biphenyl) -2,5-diol], 1,1'-(diphenyl) -2,5-diol [1,1 '-(diphenyl) -2,5- diol]
It is called etc. Its chemical formula is C ₁₂ H ₁₀ O ₂ , and its structural formula is shown by the following formula.

[0008]

Embedded image

In preparing the cosmetic of the present invention, the amount of phenylhydroquinone is not particularly limited, but is preferably 0.1 to 5% by weight, more preferably 0.25% by weight, based on the total weight.
It can be ~ 2% by weight. This amount is more effective at lower concentrations when used in conjunction with a suitable base that enhances skin absorption and retention. The content is 5% by weight.
If it exceeds, vitiligo may occur in long-term use.

The cosmetic of the present invention can be prepared as a cream, an emulsion, a pack, a lotion, etc. by a known method. In addition, the types and amounts of the constituent components that can be used in the preparation of the cosmetics of these various aspects can be appropriately determined according to conventional examples known to those skilled in the art.

The types and amounts of these components are not limited, and may be any types and amounts known to be capable of preparing the cosmetic of the intended embodiment. it can. In the preparation of such cosmetics, conventional melanin production inhibitors, ultraviolet absorbers, ultraviolet scattering agents,
An anti-inflammatory agent, a vitamin agent, a steroid agent and the like may be combined.

Phenylhydroquinone, which is an active ingredient of the present invention, is susceptible to oxidation due to light and temperature rise, and when a preparation containing phenylhydroquinone becomes alkaline, and thus lacks some stability. Therefore, store in a cool, dark place, or an antioxidant (eg, ascorbic acid, dibutylhydroxytoluene, citric acid, propyl gallate, tocopherol, etc.) or a drug that makes the base of the preparation acidic (for example,
Sodium bisulfite, citric acid, ascorbic acid, etc.)
Can increase the stability.

The skin whitening and melanin-inhibiting effects of phenylhydroquinone, which is an active ingredient of the cosmetic of the present invention, are about twice as strong as hydroquinone in each test example described below. Found that their effects were not observed. In addition, phenylhydroquinone does not cause vitiligo remaining as a side effect unless high concentrations are used continuously over a long period of time.

[0014]

The present invention will be further described with reference to the following examples and test examples, but the scope of the present invention is not limited by these examples. [Example 1] (liquid cream)

[Example 2] (Lotion)

Example 3 (Cold cream)

Experimental animals, test substances, application methods and evaluation methods of skin whitening used in the following test examples are shown below.

[Reference Example] Experimental animals Black guinea pigs JY-4 (introduced to the Tokyo Metropolitan Institute of Public Health from the National Institute of Preventive Health in 1984, and maintained by sibling breeding). Was. In this animal, dopa (L-β-3,4-dihydroxy
It has activated melanocytes positive for phenylalanine (DOPA) and its skin color is black-gray.

2. Test substances Phenylhydroquinone and orthophenylphenol, hydroquinone, arbutin and kojic acid were used as comparative control substances. Each concentration of the test substance was adjusted by W / V% (indicating the content [g] in 100 ml).

3. Coating method A portion of the back skin obtained by shaving the hair with a hair clipper and a shaver was divided into squares of 4 × 4 cm or 4 × 3 cm with a black marker (the former was 6 places per animal, and the latter was 8 places per animal). With a micropipette in the compartment, 10
0 μl of the test substance solution and its solvent once a day for 6 weeks
Application for 5 consecutive days. The hair at the application site was shaved once a week. In addition, for the recovery test of the whitened skin, a group was applied for 13 consecutive weeks.

4. Evaluation of skin whitening To examine skin whitening, the whiteness was determined using the following evaluation method. Four-step evaluation method:-: No whitening is observed ±: Slight whitening is observed +: Sufficient whitening is observed ++: Remarkable whitening is observed Further, the experiments of Test Examples 3 to 5 are visually white. The evaluation was made using a spectrophotometer (CM-2022, manufactured by Minolta Camera Co., Ltd.).

Evaluation of skin color by spectrophotometer: The color system was measured using L * a * b * standardized by the International Commission on Illumination (CIE) in 1976. L * represents lightness, a * and b * represent chromaticity indicating hue and saturation, and the L * value can be expected to be a value roughly proportional to the melanin content of the skin in an appropriate range. L * value was measured by automatic averaging using 5 instruments in one section, and the average value ± standard deviation per 4 guinea pigs in each group was calculated. A significance test was performed.

[Test Example 1] (Study on skin whitening effect of phenylhydroquinone and orthophenylphenol) Skin whitening of phenylhydroquinone, which is an active ingredient of the cosmetic of the present invention, and orthophenylphenol which has been reported in the literature so far. An experiment was conducted to evaluate the effect on the chemical action.

[0024] The results are shown in Table 1 (see FIG. 1).

[0025]

[Table 1]

As shown in Table 1 and FIG. 1, orthophenylphenol did not have a skin whitening effect, and phenylhydroquinone did.

[Test Example 2] (Recovery test of skin whitened by phenylhydroquinone) After continuous application of phenylhydroquinone, the skin in the section whitened by phenylhydroquinone was allowed to stand for a certain period of time to recover the original skin color. It was examined whether or not it recovered.
The application period was 5 weeks and the group of animals was completed with one more application.
Groups of animals that lasted up to 3 weeks were made, each of which was housed untreated for an additional 13 weeks and examined for color. Table 2 shows the results.

[0028]

[Table 2]

As shown in Table 2, one of the groups to which a 5% phenylhydroquinone solution (solvent: ethanol) was applied for 13 weeks was used.
The animals showed slight residual vitiligo, and the whitening disappeared and returned to the original skin color in the other groups.

[Test Example 3] (Comparative study 1 on the skin whitening effect of phenylhydroquinone and hydroquinone) The active ingredient of the cosmetic of the present invention, phenylhydroquinone, and hydroquinone, which is known to have a melanin production inhibitory effect, For both cases, an experiment was performed to compare the skin whitening effect.

[0031] Table 3 shows the results of the macroscopic evaluation, and Table 4 shows the results of evaluation by a spectrophotometer (see FIG. 2).

[0032]

[Table 3]

[0033]

[Table 4]

As shown in Tables 3 and 4 and FIG. 2, phenylhydroquinone is stronger than hydroquinone (approximately 2
It has a skin whitening effect.

[Test Example 4] (Comparative study 2 on skin whitening effect of phenylhydroquinone and hydroquinone) Phenylhydroquinone and hydroquinone were compared at a higher concentration than the experiment of Test Example 3. Table 5 shows the visual judgment of the result, and Table 6 shows the evaluation by a spectrophotometer (see FIG. 3).

[0036]

[Table 5]

[0037]

[Table 6]

As shown in Tables 5 and 6 and FIG. 3, phenylhydroquinone is stronger than hydroquinone (approximately 2
It has a skin whitening effect.

[Test Example 5] (Comparison study of skin whitening effect of phenylhydroquinone and kojic acid and arbutin) It is known that phenylhydroquinone, which is an active ingredient of the cosmetic of the present invention, has an effect of inhibiting melanin production. Experiments were conducted to compare skin whitening effects using kojic acid (see JP-A-63-270619) and the hydroquinone derivative arbutin (see JP-A-60-16906).

Test substance: 4%, 1% phenylhydroquinone solution 4%, 1% arbutin solution 4%, 1% kojic acid solution Solvent: dimethyl sulfoxide: Ethanol 1: 4 mixed solution 5 weeks The results are shown in Table 7 and the evaluation by spectrophotometer is shown in Table 8 (see FIG. 4).

[0041]

[Table 7]

[0042]

[Table 8]

As shown in Tables 7 and 8 and FIG. 4, phenylhydroquinone has a stronger skin whitening effect (more than 4 times) than arbutin and kojic acid.

Test Example 6 (Microscopic observation of epidermal melanocytes on the vertical surface of the skin) The skin of the experiment in Test Example 5 was collected, embedded in an embedding medium for preparing frozen sections, and frozen with liquid nitrogen. For the tissue, a cryostat (cryostat) was used to prepare a frozen section specimen, fixed with 10% neutral buffered formalin solution for 5 minutes, washed with water,
37 ° C with 0.1% dopa solution (solvent: phosphate buffer of pH 6.8)
For 6 hours. Thereafter, the cells were washed with water, subjected to nuclear staining with Kernechtrot, dehydrated, sealed with a mounting agent, and observed with an optical microscope. As a result, epidermal dopa-positive melanocytes were observed in both the 1% and 4% concentration groups of arbutin and kojic acid and the 1% group of phenylhydroquinone with little change compared with the solvent control group, but the phenylhydroquinone 4% The percentage significantly decreased in the% group. The results of optical microscopic observation of the 4% group of arbutin, kojic acid, and phenylhydroquinone are shown in FIGS.

In the electron microscopic observation of the 5% phenylhydroquinone-applied group, the solvent control group, and the untreated group in Test Example 1, skin tissue debris of each group was examined using 2% glutaraldehyde / 1% osmate. Fixed by double fixation method, dehydrated in ethanol ascending series, embedded in epoxy resin, polymerized, ultra-thin sliced, and stained with uranium acetate / lead citrate double electron and observed with transmission electron microscope And shot. As a result, in the skin to which 5% phenylhydroquinone was applied, a clear decrease in the number of melanosomes in the endoplasmic reticulum vesicles and a destruction image of the remaining melanosomes were observed. No such image was observed in the untreated group and the vehicle control group. 8 and 9 show electron microscope images of skin melanocytes in the 5% phenylhydroquinone group and the untreated group, respectively.

From the literature, the inhibitory effect of arbutin and kojic acid on melanin production is considered to be the inhibition of the activity of the tyrosinase enzyme required for melanin production (Akiho Akira et al., The inhibitory effect of arbutin on melanin production; Research, Journal of the Japanese Dermatological Association, 101, 609-613,
1991 and Takashi Higa, and Kojic acid on melanin production inhibitory action, Fragrance Journal, 63, 40-44, 1983). However, the action of hydroquinone has been described by Jimbow et al. (J. Inves
t. Dermatol., 62, 436-449, 1974) reported from observations with an electron microscope that melanin production was inhibited by melanocyte injury with relatively high selectivity. With this application of phenylhydroquinone, skin whitening of phenylhydroquinone was observed based on macroscopic observation of skin whitening, histological observation of marked reduction of dopa-positive melanocytes in the epidermis, and electron microscopic observation of destruction of melanosomes. It is certain that the formation is due to the marked suppression of melanogenesis of epidermal melanocytes.

[0047]

According to the present invention, stains due to sunburn etc.
A novel cosmetic that prevents the occurrence of freckles and black and white, has a strong whitening effect, and is excellent in safety is provided.

[Brief description of the drawings]

Fig. 1 shows the appearance (organism form) of the back skin of black guinea pig JY-4 to which a 1% and 5% solution of phenylhydroquinone, a 1% and 5% solution of orthophenylphenol and a solvent (ethanol) were applied for 5 weeks. It is a photograph shown.

FIG. 2: Appearance of the back skin of a black guinea pig JY-4 to which a 0.25%, 0.5%, 1% solution of phenylhydroquinone, a 0.25%, 0.5%, 1% solution of hydroquinone and a solvent (ethanol) were applied for 5 weeks FIG.

FIG. 3 shows a 1%, 2%, 4% solution of phenylhydroquinone, a 1%, 2%, 4% solution of hydroquinone and a solvent (ethanol).
1 is a photograph showing the appearance (organism form) of the back skin of black guinea pig JY-4 applied for 5 weeks.

FIG. 4 shows a 1%, 4% solution of phenylhydroquinone, a 1%, 4% solution of arbutin, a 1%, 4% solution of kojic acid and a solvent (a mixture of dimethyl sulfoxide: ethanol of 1: 4).
1 is a photograph showing the appearance (organism form) of the back skin of black guinea pig JY-4 applied for 5 weeks.

FIG. 5 is a photomicrograph showing a tissue image of a frozen skin specimen prepared from a portion of the back skin of black guinea pig JY-4 to which 4% arbutin was applied for 5 weeks, and subjected to Dopa reaction and nuclear staining with Cologne-Echthroat. It is.

FIG. 6: A frozen tissue specimen was prepared for the back skin of black guinea pig JY-4 at the portion where 4% kojic acid was applied for 5 weeks.
It is a microscope picture which shows the tissue image which performed the Dopa reaction and the nuclear staining by the Koln-Echthrot.

FIG. 7 is a microscope showing a tissue image of a frozen tissue specimen prepared from a portion of the back skin of black guinea pig JY-4 to which 4% phenylhydroquinone has been applied for 5 weeks, and subjected to Dopa reaction and nuclear staining with Cologne-Echthroat. It is a photograph.

FIG. 8 Glutaraldehyde / osmic acid double fixation on the back skin of black guinea pig JY-4, to which 5% phenylhydroquinone was applied for 5 weeks, embedded in epoxy resin to prepare an electron microscope sample, and epidermis 3 is an electron micrograph of melanocytes.

FIG. 9 is an electron microscope in which an untreated portion of the back skin of a black guinea pig JY-4 is double-fixed with glutaraldehyde and osmate and embedded in an epoxy resin to prepare an electron microscope sample, and photographed epidermal melanocytes. It is a photograph.

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[Procedure amendment]

[Submission date] December 6, 1996

[Procedure amendment 1]

[Document name to be amended] Drawing

[Correction target item name] All figures

[Correction method] Change

[Correction contents]

FIG.

FIG. 2

FIG. 3

FIG. 4

FIG. 5

FIG. 6

FIG. 7

FIG. 8

FIG. 9

Claims (1)

[Claims] 1. A cosmetic containing phenylhydroquinone as an active ingredient.