JPH10139654A - Composition for external skin use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a composition for external skin use excellent in skin beautifying and whitening actions, safety and stability without causing skin rash by including a substance capable of inhibiting or suppressing activities of tyrosinases, a specific extract and a flavonoid extract from Glycyrrhizae Radix therein. SOLUTION: This composition for external skin use comprises (A) preferably 0.05-10wt.% substance capable of inhibiting or suppressing activities of tyrosinases such as an ellagic acid-based compound, (B preferably 0.1-10wt.% extract selected from soybean (meal) or a fermentation product obtained by using the soybean (meal) as a raw material and (C) preferably 0.01-10wt.% flavonoid extract from Glycyrrhizae Radix or its ingredient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a composition for external use on skin having an excellent skin whitening effect.

[0002]

2. Description of the Related Art There are many unclear points about the mechanism of pigmentation such as skin spots and freckles, but in general, abnormalities of hormones and stimulation by ultraviolet rays cause excessive production of melanin pigment, It is believed to be abnormally deposited within. For the purpose of preventing or improving such pigmentation, conventionally, hydrogen peroxide, zinc peroxide, peroxides such as magnesium peroxide, or ascorbic acid, glutathione, colloidal sulfur, various natural products and the like as an active ingredient. Attempts have been made to use whitening cosmetics. However, many of these active ingredients have insufficient safety and stability, or have problems with odor and the like, and their effects are not necessarily sufficient. On the other hand, in the United States and the like, hydroquinone is used as a skin depigmenting agent, but this hydroquinone has irritation and allergic properties, and there is a problem in terms of safety in formulating it as an active ingredient in cosmetics. . Therefore, various studies have been conducted to develop cosmetics having a skin whitening effect without such disadvantages.

[0003] By the way, skin pigmentation such as spots and freckles is considered to be a major factor due to excessive production of melanin pigment. Tyrosinase is the most important enzyme that works for the production of melanin pigment. Tyrosinase is an enzyme that oxidizes tyrosine, which is a raw material of melanin pigment. Studies have been made to inhibit or suppress the action of this enzyme to suppress the production of melanin pigment. As a result, crude drug extracts such as mulberry bark, Senkyu, Toki, cinnamon bark, summer hay, etc. (Fragrance Journal 1990
June issue p. 59), an external whitening agent using kojic acid and a kojic acid derivative (JP-A-53-3538, JP-B-56-18569, JP-B-58-22151, JP-A-60-9722, and 61-). 60801), a cosmetic containing quercetin as an active ingredient (JP-A-5
No. 5-92305), cosmetics containing a fatty acid ester of quercetin as an active ingredient (JP-A-58-131911).
Japanese Patent Application Laid-Open No. 52-44375), and cosmetics containing catechin having a polyphenol skeleton as an active ingredient and the like are disclosed. However, in all of these cosmetics, in actual use, the stability of the whitening component is still insufficient, or the effect is recognized at the cellular level, but the effect is not sufficiently exhibited in humans However, it is not always satisfactory.

[0004] The flavonoid extract of licorice is also referred to as an oil-soluble licorice extract, which is mainly composed of glabridine and has been reported to suppress the production of melanin (Japanese Journal of Dermatology 102 (6)). ) 679 (19
92)). However, it has been pointed out that the whitening effect has a limit, and that it causes irritation to the skin.

Accordingly, the present inventors have overcome the drawbacks of the conventional skin whitening preparations for the purpose of whitening, are excellent in skin whitening effect, are high in safety, and have high stability and odor. For the purpose of providing a skin external preparation with no problem, as a result of earnestly searching for those which inhibit or suppress tyrosinase activity having the most important role in the production of melanin pigment, those having a polyphenol skeleton, especially ellagic acid compounds and They found that the alkali metal salt was excellent and proposed it earlier (Patent Registration 1839986).
issue). The present inventors have further studied and found that, even when the particularly excellent ellagic acid-based compound or its alkali metal salt is incorporated into a cosmetic or quasi-drug base, it can be converted into a normal external preparation. It was found that the effect was not always sufficient at the compounding concentration of.

[0006]

SUMMARY OF THE INVENTION An object of the present invention is to provide a composition for external use on the skin which is excellent in skin whitening action and also excellent in safety and stability.

[0007]

In view of the above circumstances, the present inventors have formulated a substance that inhibits or suppresses tyrosinase activity, in particular, a substance having a polyphenol skeleton, especially the above-mentioned ellagic acid-based compound or an alkali metal salt thereof. As a result of repeated studies for the purpose of improving the skin whitening effect of the prepared formulation, such a substance and soybean, soybean meal, preferably an extract and / or extract of those selected from those fermented using these as raw materials The present inventors have found that when a licorice flavonoid extract or a component thereof is used in combination, the whitening effect is remarkably improved without irritation to the skin, and the present invention has been completed.

That is, according to the present invention, a substance (A component) that inhibits or suppresses tyrosinase activity and an extract (B component) of soybean, soybean meal, or a material selected from those fermented using these as a raw material And / or a flavonoid extract of licorice or a component thereof (component (C)).

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, each component of the composition for external use on skin of the present invention will be specifically described. The substance that suppresses or inhibits tyrosinase activity, which is the A component of the active ingredient of the external composition for skin of the present invention, is a single compound and a mixture, for example, a natural product extract. , Senki, Toki, cinnamon bark, summer hay and other herbal extracts (Fragrance Journal 1990 6
Monthly p. 59), compounds such as ascorbic acid, arbutin, kojic acid, and the like. Examples of the substance having a polyphenol skeleton include catechin, tannin, and lignin (Japanese Society of Agricultural Chemistry 69 (9) 1183 (1)
995)) and ellagic acid compounds and alkali metal salts thereof. Of these, substances having a polyphenol skeleton, particularly ellagic acid-based compounds and alkali metal salts thereof are preferred because of their excellent effects.

The ellagic acid compound and the alkali metal salt thereof are represented by the following general formula.

Embedded image (In the formula, R ¹ , R ² , R ³ , and R ⁴ are a hydrogen atom, and have 1 to 2 carbon atoms.
0 alkyl group, acyl group having 1 to 20 carbon atoms, formula-(Cm
H ₂ m-O) nH (although, m is 2 or 3, n is a polyoxyalkylene group, or the formula represented by an integer of 1 or more)

Embedded image Which may be the same or different from each other, and R ⁵ represents a hydrogen atom, a hydroxyl group or an alkoxy group having 1 to 8 carbon atoms. )

In the general formula (I), R ¹ , R ² ,
When R ³ and R ⁴ are an alkyl group having 1 to 20 carbon atoms, specific examples thereof include a methyl group, an ethyl group, and a propyl group, and a methyl group and an ethyl group are particularly preferable. When R ¹ , R ² , R ³ and R ⁴ are an acyl group having 1 to 20 carbon atoms, specific examples thereof include an acetyl group and a propionyl group. Further, R ¹ , R ² , R ³ , and R ⁴ are
- If it is _{(CmH 2 m-O) nH} , and specific examples thereof include
A polyoxyethylene group or a polyoxypropylene group, and n is an integer of 1 or more, and particularly preferably 5 to 40. R ¹ , R ² , R ³ , and R ⁴ may be the same or different from each other. Further, when R ⁵ is an alkoxy group having 1 to 8 carbon atoms, specific examples thereof include a methoxy group, an ethoxy group, a propoxy group and the like, and a methoxy group is particularly preferable. Furthermore, examples of the alkali metal salts of these ellagic acid compounds include sodium salts and potassium salts.

The ellagic acid compounds of the present invention include, for example, R ¹ , R ² , R ³ , R ⁴ and R ^{5 in the} general formula (I).
Is preferably a ellagic acid in which R ¹ , R ² , R ³ and R ⁴ are a hydrogen atom, a methyl group or an ethyl group, and R ⁵ is a hydrogen atom, a hydroxyl group or a methoxy group. Further, ellagic acid in which a part of the phenolic hydroxyl group is converted to a sodium salt or a potassium salt is preferable in terms of good solubility. The ellagic acid-based compound and the alkali metal salt thereof are further added with the compound represented by the general formula (I) in order to adjust its lipophilicity or hydrophilicity in preparing a composition for external use on the skin.
Some of R ¹ , R ² , R ³ and R ^{4 in} the formula are a long-chain alkyl group having up to 20 carbon atoms, a long-chain acyl group having up to 20 carbon atoms,
Selected from the sugar residue represented by the formula _{(CmH 2 m-O-) nH} ( where m is 2 or 3, n is an integer of 1 or more) polyoxyalkylene group and the structural formula represented by (II) R ⁵ may be substituted with a long-chain alkoxy having up to 8 carbon atoms.

Specific examples of the ellagic acid-based compound and the alkali metal salt thereof include ellagic acid (R ¹ , R ² , R ³ , R ⁴ , R ^{5 in the} general formula (1): hydrogen atom); 4-di-o
-Methylellagic acid (in the general formula (1), R ¹ : methyl group, R ² : methyl group, R ³ : hydrogen atom, R ⁴ : hydrogen atom,
R ⁵ : hydrogen atom), 3,3′-di-o-methylellagic acid (in the general formula (1), R ¹ : hydrogen atom, R ² : methyl group,
R ³ : hydrogen atom, R ⁴ : methyl group, R ⁵ : hydrogen atom), 3,
3 ′, 4-tri-o-methylellagic acid (in the general formula (1),
R ¹ : methyl group, R ² : methyl group, R ³ : hydrogen atom, R ⁴ :
Methyl group, R ⁵ : hydrogen atom, 3,3 ′, 4,4′-tetra-o-methyl-5-methoxyellagic acid (in the general formula (1), R ¹ :
Methyl group, R ² methyl group: R ³ : methyl group, R ⁴ : methyl group, R ⁵ : methoxy group), 3-o-ethyl-4-o-methyl-5-
Hydroxyellagic acid (in the general formula (1), R ¹ : methyl group, R ² : ethyl group :, R ³ : hydrogen atom, R ⁴ : hydrogen atom, R ⁵ : hydroxyl group), amritoside (Amritoside) (general formula ( In I), R ¹ : the above-mentioned structural formula (II), R ² : hydrogen atom, R ³ : hydrogen atom, R ⁴ : hydrogen atom, R ⁵ : hydrogen atom)
And alkali metal salts of these compounds.

These ellagic acid compounds include strawberry, cod (Caesalpinia spinosa) and eucalyptus wood (Eucalyptu).
s), apples, poisonous azaleas (Korea yaponica), radiata pine, bear bearberry, pomegranate, anmarok, ukyuyouyou, enfuyou, kaijicha, kakojuyou, oak, kiju, kenjin, kounaka, sanukyukon,
Sankyu, Shufuboku, Senkutsusai, Sougenroukansou, Daihyousou, Domouanyou, Haouben, Banseki Ryukan, Banseki Ryuhi, Bouka, Moshoshikushi, Yatuseika, Yatou Seiyu, Yukankon, Yukanbokuyu, Yukanyukou, Yukanyukyouyu Compilation,
It can be easily obtained from natural products such as sidocon, chinsou and gennoshoko by the following method (see Japanese Patent Publication No. 53-14605).

That is, a dried and pulverized product of the above natural product containing an ellagic acid compound is digested by a usual acidic sulfite method, and then immersed in an aqueous alkali solution of sodium hydroxide or sodium carbonate (pH 10 to 13). After collecting the immersion liquid,
The pH is adjusted to 2 to 8 by adding an acid such as sulfuric acid or acetic acid to the immersion liquid to obtain a precipitate mainly composed of ellagic acid. This precipitate is collected by centrifugation or the like, and further washed with water to remove impurities and obtain highly pure ellagic acid. In addition, the ellagic acid-based compound is widely present in natural products as described above, and it is considered that the safety is extremely high.However, when safety was confirmed just in case, acute toxicity, skin irritation, No practical problems were observed in terms of skin sensitization and mutagenicity, and the safety was confirmed to be high.

In the present invention, one or more of these compounds, or a mixture thereof or a natural product extract, which suppresses or inhibits the tyrosinase activity, which is the component A, may be used arbitrarily. The content is 0.001 to 30% of the whole skin external composition (% is% by weight, the same applies hereinafter).
Is more preferable, and more preferably 0.05 to 10%.

In the composition for external use on the skin of the present invention, in order to improve the whitening effect of the component A, the component B
An extract of soybean, soybean meal, or those selected from those fermented using these as a raw material is used. The soybeans used as raw materials can be of any variety, cultivation area, cultivation / harvest time, grain appearance, properties and size, protein, fat, carbohydrate, etc. (For soybeans, for example, Fukuba Hirobo Daisensho "Soybean", Women's Nutrition University Press (1984)).
After harvesting, pretreatments such as drying, degreasing, deproteinization, and crushing may be performed, but those which have been subjected to a treatment such as steaming and undergoing a fermentation process are preferred.

The term "fermentation" used herein refers to the action of a microorganism or a metabolite thereof. That is, microorganisms such as bacteria (such as Bacillus), yeasts (such as Saccharomyces), and fungi (such as Aspergillus) can be added to soybeans or soybean meal that have been subjected to pretreatment such as washing, immersion, steaming, and crushing as necessary. And incubate at an appropriate temperature. At this time, the number of the microorganisms may be one or more, or may be changed during the culture. Microorganisms may be directly inoculated or added in the form of koji. Therefore, in addition to soybeans, organic substances and salts such as rice and wheat, or water may be added. The culture method can be either solid or liquid, or it can be agitated
You may shake it. Further, the treatment may be performed using an extract or metabolite of a microorganism. Further, miso, soy sauce, natto, tempe, milk tofu, etc. are known as fermented products of soybeans, but these may be used as raw materials.

The extraction is carried out with stirring, shaking, standing or circulating using an organic solvent such as water or ethanol, or a mixture thereof. Supercritical extraction with carbon dioxide is also possible. Note that "B"
Although it is possible to use it as a “component,” a composition for external use on the skin is largely restricted in its effects, handling, appearance, feeling of use, and the like.

It should be noted that the extract of miso has an effect of inhibiting melanin production of melanoma cells (Miso Science and Technology 4
3 (2) 68 (1995)) and that the active ingredient is present in the non-dialysis fraction (Japanese Society of Food Science and Technology 43 (6) 712).
(1996)). However, a whitening effect that can be expected at a practical level is not recognized.

In the present invention, the concentration of the component B is as follows:
As a fraction from which the extraction solvent has been removed, 0.001 to 50% of the total composition for external use on skin is preferable, and 0.01 to 20% is further preferable.
%, Particularly preferably 0.1 to 10%.

In the composition for external use on the skin of the present invention,
A licorice flavonoid extract or a component thereof is used as the component C in order to improve the whitening effect of the component A. The licorice flavonoid extract is also called an oil-soluble licorice extract, and its main component is glabridine. In the present invention, an extract may be used as the C component, or a component itself such as glabridine contained in the extract may be used.

In the present invention, the concentration of the C component is
It is preferably 30% or less, more preferably 0.001 to 20%, particularly preferably 0.01 to 10% of the whole skin external composition.
Is preferred.

In the external composition for skin of the present invention, the component A, the component B and / or the component C are used in combination, but it is preferable to use the component A in combination with the component B and the component C.
The ratio of the concentration of “A component” and “B component” and / or “C component” of the external composition for skin of the present invention is as follows:
1: 50,000-5000: 1 is preferred, and further 1:
4000 to 100: 1 is preferable, and especially 1: 200 to 5
0: 1 is preferred.

[0025] In addition to the above-mentioned "Component A", "Component B" and "Component C", the composition for external use on the skin of the present invention may further comprise, if necessary,
As long as the effects of the present invention are not impaired, various components usually used in external preparations for skin, for example, oils, water, surfactants, moisturizers, alcohols, thickeners, antioxidants, metal ions Blocking agents, pH adjusters, preservatives, fragrances, pigments, ultraviolet absorbers, ultraviolet scattering agents, vitamins, amino acids, and the like can be added.

The above-mentioned composition for external use on the skin is a wide-range base such as an aqueous solution system, a solubilizing system, an emulsifying system, a powder dispersion system, a water-oil two-layer system, a water-oil-powder three-layer system, and the like. Its uses are also basic cosmetics such as creams, milky lotions, lotions, serums, and packs,
It can be widely and suitably used in various forms such as makeup cosmetics such as lipsticks and foundations, pharmaceuticals such as jellies and ointments and quasi-drugs.

[0027]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail based on embodiments. First, the following various B components of the composition for external use on skin of the present invention were prepared. [Component B-1] Dried “Tsurunoko soybeans” are crushed well with a mallet, and then 100 ml of ethanol is added thereto and the mixture is added at room temperature for 20 minutes.
Stirred well for hours. After filtration, the solvent was distilled off under reduced pressure to obtain 2.1 g of an extract. [B-2 component] 30% ethanol 1 in 10 g of commercially available miso
After adding 00 ml, the mixture was stirred well at room temperature for 20 hours. After filtration, the solvent was distilled off under reduced pressure, and dried in a desiccator to obtain 1.5 g of an extract. [B-3 component] 100 ml of ethyl acetate was added to 100 ml of commercially available brewed soy sauce, and the mixture was shaken well with a separating funnel. After standing, the solvent part including the boundary part was recovered. Extraction was performed again in the same manner, and the recovered solvent was distilled off under reduced pressure, and then dried in a desiccator to obtain 0.4 g of an extract. [Ingredient B-4] Steamed defatted soybeans are crushed, and Rhizopus
arrhizus was inoculated and fermented at 40 ° C. for 3 days. 100 ml of 30% ethanol was added to the 10 g, and the mixture was stirred well for 20 hours. After filtration, the solvent was distilled off under reduced pressure, and dried in a desiccator to obtain 1.4 g of an extract. [Component C] As the flavonoid extract of licorice, those described in the standard specification of cosmetic ingredients (cosmetic regulation) were used.

Example 1 2.5 × 10 ⁴ B16 melanoma cells were seeded on a 6-well plastic microplate and cultured at 37 ° C. for 2 days in the presence of 5% CO ₂ , and then the medium was replaced. At the same time, the A component and the B component were added, and the mixture was further cultured for 2 days. After completion of the culture, the medium was discarded, the cells were detached from the plate with a trypsin solution, transferred to an Eppendorf tube, and collected by centrifugation. After washing with phosphate buffered saline,
The color change of the cells was observed. Table 1 shows the results. The skin whitening effect was evaluated based on the following criteria by comparing the change in the color of the cells with the color of the cells to which no A component, B component, or C component had been added. ±: slight fading +: fading ++: fairly fading +++: marked fading

[0029]

[Table 1] As is clear from Table 1, when the component B and / or the component C are used in combination, the color of the B16 melanoma cells is significantly faded as compared with the component A alone.

Example 2 A whitening agent (1) in which ellagic acid was used as the component A and the component A was dissolved in propylene glycol at 1.0%;
Whitening agent (2) in which components were dissolved in propylene glycol 1.0%, whitening agent (3) in which components A and B-1 were each dissolved in 0.5% in propylene glycol, and component B-2 in propylene glycol 1. Whitening agent (4) dissolved in 0%, A
Component and B-2 component in propylene glycol for 0.5
% Dissolved whitening agent (5), whitening agent (6) in which component B-4 was dissolved in propylene glycol 1.0%, component A and component B-
A whitening agent (7) in which each of the four components was dissolved in propylene glycol at a concentration of 0.5% was prepared and subjected to a test (7 animals per group). The evaluation of the skin whitening effect was performed according to the methods and evaluation criteria shown below. Table 3 shows the results. The numbers in Table 3 indicate the Munsell values (average of seven animals) of each test sample and control sample application.

[Whitening Evaluation Method] The back body hair of a colored guinea pig is shaved with a hair clipper and a shaver, and irradiated with ultraviolet rays once a day for a total of eight times, so that the back of each guinea pig has an area of about 2.25 cm ² . Were made in two places.
20 μl of the test sample and the control sample were applied once a day, 5 times a week for 4 weeks, and the brightness change of the pigmentation was checked once a week by the standard color chart (Japan Color Research Institute, “Neutral Value Scale 3”).
8 "). Then, the brightness difference was calculated from a value converted into a Munsell value described in “Neutral Value Scale 38”. This "brightness difference"
It shows how much the change in lightness of the pigmentation approaches the skin color without pigmentation due to UV irradiation compared to the control (only propylene glycol was applied). The evaluation was based on the criteria in Table 2.

[0032]

[Table 2]

[0033]

[Table 3] As is evident from Table 3, the whitening effect is remarkably improved when the soybean as the component B, particularly an extract obtained by fermenting soybean, is used in combination with the ellagic acid as the component A alone.

Example 3 The oil phase component and the aqueous phase component shown in Table 4 were separately heated and dissolved at 70 ° C., and then mixed and emulsified. While cooling, a fragrance was added on the way, and the mixture was further cooled to room temperature to prepare an emulsion. did.

[0035]

[Table 4]

The effectiveness of the emulsion thus prepared was evaluated as follows. That is, the product of the present invention and the comparative example were applied twice a day for 5 weeks to the pigment spots of 10 men and women with pigment spots (stains), and the whitening effect was examined 5 weeks later. Table 5 shows the results. The whitening effect was evaluated according to the following criteria. Significant effect: Pigmentation became almost inconspicuous. Effective: Pigmentation was very thin. Somewhat effective: Pigmentation was slightly lighter. Invalid: No change

[0037]

[Table 5] From the results in Table 5, it was found that the emulsion of the present invention, in which the component A and the component B coexist, clearly has a superior whitening effect as compared with the comparative example alone. In addition, 5 of the above emulsion
During and after weekly use, no abnormality was observed in the skin condition.

Example 4 A serum was prepared by mixing the components shown in Table 6.

[Table 6]

The effectiveness of the thus-prepared cosmetic serum of the present invention was the same as in Example 3 (however, the test period was 6
Weeks). Table 7 shows the results.

[Table 7] From the results shown in Table 7, it was found that the serum of the present invention, in which the components A and B coexist, was clearly superior in whitening effect as compared with the comparative example alone. In addition, no abnormality was observed in the condition of the skin during and after the use of the serum for 6 weeks.

Example 5 After the oil phase component and the aqueous phase component shown in Table 8 were separately dissolved at 70 ° C., the solution was mixed and emulsified while stirring, and cooled to room temperature to prepare a cream shown in Table 8. did.

[Table 8]

The effectiveness of the cream thus prepared was evaluated as follows. That is, pigment spots (stains)
10 creams each containing 10 pigmented spots
The whitening effect after applying 25 g once a day every day for 6 weeks was examined. The evaluation of the whitening effect was performed in the same manner as in Example 3. Table 9 shows the results.

[Table 9] From the results in Table 9, it was found that the creams of the present invention, in which the component A and the component B coexist, were clearly superior in whitening effect as compared with the comparative examples alone. No abnormality was found in the condition of the skin during and after use of the cream.

[0042]

EFFECTS OF THE INVENTION The composition for external use on the skin of the present invention comprises an extract of soybean, soybean meal or a fermented product thereof, which is a substance inhibiting or suppressing tyrosinase activity.
Or, because a flavonoid extract of licorice or a component thereof is blended, its skin whitening effect is significantly enhanced as compared with a substance using a substance that inhibits or suppresses tyrosinase activity alone, and furthermore, there is no skin irritation and the like. It has good gentle safety and good stability.

Claims (1)

[Claims] 1. A substance (A component) that inhibits or suppresses tyrosinase activity, and an extract (B) of soybean, soybean meal, or a substance selected from those fermented using these as a raw material.
And / or a flavonoid extract of licorice or a component thereof (component (C)).