JPH06336419A - External agent for skin - Google Patents

Abstract

PURPOSE:To obtain an external agent for skin having excellent active oxygen scauenging action and exhibiting stable and excellent effect on the improvement of chapped skin, prevention of skin aging, etc. CONSTITUTION:This external agent for skin such as cosmetics and pharmaceuticals contains proanthocyanidin existing in grape extract, etc., and an active oxygen scauenging agent and/or antioxidant as active components. The external agent exhibits extremely high preventive effect on the formation of lipid peroxide, inflammation, melanism, aging, etc., of the skin caused by the formation of active oxygen in the skin by the exposure to ultraviolet rays and is extremely useful for beauty and medical care.

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, and more specifically, to prevent the production of lipid peroxides, skin inflammation, blackening, aging, etc. due to active oxygen production in the skin. The present invention relates to an external preparation for skin such as cosmetics and pharmaceuticals, which has an excellent effect of preventing skin aging and an effect of improving rough skin.

[0002]

2. Description of the Related Art Blackening of the skin caused by sunburn or the like and spots and freckles caused by pigmentation are major problems for women, and there has been a demand for the development of a whitening cosmetic composition which prevents such a phenomenon.

Conventionally, as the active ingredients blended in whitening cosmetics, ascorbic acid, glutathione, colloidal sulfur, hydroquinone, kojic acid, cinnamic aldehyde and the like have been known, but those having a strong whitening effect are known.
There are problems in terms of stability, odor, safety, etc. On the contrary, those without these problems have the drawback of weak whitening effect, and it was difficult to say that all of them were sufficiently satisfactory.

On the other hand, external preparations for skin such as cosmetics are also required to have the functions of improving rough skin and preventing skin aging. As medicinal ingredients having such an action, allantoin, aloe extract and ginseng extract are required. , Placenta extracts, bovine blood deproteinization products, fermentation metabolites and the like are known.

However, the skin external preparations containing these medicinal components cannot practically exhibit sufficient effects for improving rough skin and preventing skin aging, and development of a skin external preparation having more excellent action is desired. Was there.

[0006] Among them, proanthocyanidins contained in grape extract and the like have an active oxygen removing action [J. Agric. Food Chem., 39: 1549-1552 (1991)] and an antioxidant action [JP No. 61-16982, Monthly Food Distribution Technology, 21 (2): 16-19], and procyanidin, which is one of the constituents, has a whitening effect (JP-A-2-
134309).

[0007]

[Problems to be Solved by the Invention] However, when the proanthocyanidins are blended alone, the effects on the rough skin improving action and the skin aging preventing action cannot be said to be sufficient, and due to the influence of other bases, etc. The reality is that the effect originally contained by anthocyanidins cannot be exhibited.

[0008]

In view of the above-mentioned circumstances, the inventors of the present invention have conducted diligent research in order to sufficiently bring out the skin action effect of proanthocyanidins. And as a result, for the purpose of preventing skin aging with proanthocyanidin, by using in combination with an active oxygen scavenger or an antioxidant applied to a skin external preparation, the effects on skin roughening and skin aging are synergistic. The present invention has been completed based on the finding that the original action and effect of proanthocyanidins as a skin external preparation can be stably obtained.

That is, the present invention provides a skin external preparation characterized by containing proanthocyanidin and an active oxygen scavenger and / or an antioxidant as active ingredients.

The proanthocyanidins, which are the active ingredients of the present invention, can be applied to the squeezed lees or seeds of grape fruits, torch husks, vine moss, barley, red beans, bark of pine, oak, peaches, etc. It is a compound included.

More specifically, the proanthocyanidins are condensed or polymerized with condensed tannins present in various plants as described above, that is, flavan-3-ol or flavan-3,4-diol as a constituent unit. It is a group of compounds (a mixture of oligomers), which are given this name because they produce anthocyanidins such as cyanidin, delphinidin, and pelargonidin by acid treatment.

Therefore, the proanthocyanidins of the present invention include all the dimers to the 10-mer of the above-mentioned constitutional units, and further proanthocyanidins such as polymer procyanidins, prodelphinidins and propelargonidins and stereoisomers thereof. Of these, the following formulas with excellent solubility etc. are included

[Chemical 1] (In the formula, R ₁ is hydrogen or a hydroxyl group, R _{2 to} R ₄ are each independently hydrogen, a hydroxyl group or a methoxyl group, and R ₅ is hydrogen, a galloyl group or a glycopyranosyl group). Or flavan-3,4-
2- to 10-mer, especially 2 to 4-mer proanthocyanidins having a diol as a constitutional unit can be preferably used (see JP-A-61-16982).

As the proanthocyanidins, those obtained by a synthetic method can also be used.

Proanthocyanidins are usually contained in the grape extract extracted from the squeezed lees or seeds of grape fruits in an amount of 10% or more (in terms of solid content) in terms of flavanols. Is the most economical source of proanthocyanidins. In the present invention, this grape extract will be described below as an example of a proanthocyanidin source in the present invention.

The method for extracting the grape extract containing proanthocyanidins is not particularly limited, and the raw material such as squeezed lees of grape fruits or seeds is immersed in an extraction solvent, and this is extracted at room temperature or under heating, Just filter.

Examples of the extraction solvent include water, primary alcohols such as methyl alcohol and ethyl alcohol, liquid polyhydric alcohols such as propylene glycol and 1,3-butylene glycol, lower alkyl esters such as acetic acid ethyl ester, benzene and hexane. Known solvents such as hydrocarbon, ethyl ether, and acetone can be used, and these solvents can be used alone or in combination of two or more. Among them, the preferable extraction solvent includes an aqueous solution of an organic solvent miscible with water, particularly an aqueous solution of ethyl alcohol, methyl alcohol, acetone and the like.

As the grape extract, the extract obtained by extracting as described above may be used as it is, or may be further concentrated if necessary. In addition, these extracts can be purified by a conventional method, for example, countercurrent distribution method, liquid chromatography and the like, and then used.

The content of proanthocyanidins in the external preparation for skin of the present invention is preferably 0.0001 to 5% by weight (hereinafter simply indicated as "%") in terms of flavanols.
(Preferably 0.00 as dry solids of grape extract.
01-10%, more preferably 0.01-5%). When the extract is used, the concentration of the extract is not limited as long as the content of the dry solid as a solute is within the above range.

The content of proanthocyanidins is 0.00
If it is less than 001%, a sufficient effect may not be obtained, and if it exceeds 5%, the effect is not further increased.

On the other hand, among the other essential components of the present invention, the active oxygen scavenger is other than proanthocyanidins, and includes, for example, carotenoids such as SOD, mannitol, beta-carotene, hydroquinone, bilirubin, cholesterol, tryptophan, Examples thereof include plant extracts containing flavonoids such as histidine, quercetin, quercitrin, catechin, catechin derivatives, gallic acid, gallic acid derivatives, and augon extract in its components.

Further, as the antioxidant in the present invention,
Other than proanthocyanidins, for example, vitamins A and their derivatives, such as vitamin A acetate, vitamin A palmitate, etc., and salts thereof,
Vitamin B and derivatives thereof and salts thereof, vitamin C and derivatives thereof such as phosphate-L-ascorbyl magnesium, disodium L-ascorbate sulfate, vitamin C dipalmitate and salts thereof, vitamin D and their Derivatives and salts thereof, vitamin E and derivatives thereof, such as vitamin E acetate and salts thereof, glutathione and derivatives thereof and salts thereof, BHT and BHA and the like can be mentioned. Of these, particularly preferable are SOD, beta-carotene, vitamin C and its derivatives and salts thereof, vitamin E and its derivatives and salts thereof.

The content of these active oxygen scavengers and / or antioxidants in the external preparation for skin of the present invention is generally 0.000.
It is 01 to 5%, preferably 0.001 to 3%. Content of active oxygen remover and / or antioxidant is 0.0000
If it is less than 1%, a sufficient effect may not be obtained, and if it exceeds 5%, no further increase in effect may be seen, which may adversely affect the formulation. .

The external preparation for skin of the present invention comprises, according to a conventional method, a proanthocyanidin which is an essential component and an active oxygen scavenger and / or an antioxidant, which are mixed with various forms of bases known as conventional external preparations for skin. Can be prepared.

The form of the external preparation for skin is not particularly limited, and examples thereof include cosmetics such as emulsions, creams, lotions, packs, dispersions and cleaning agents, and pharmaceuticals such as ointments, creams and liquids for external use. The base of the external preparation may be a base depending on the form of these external preparations, for example, purified water, lower alcohol, polyhydric alcohol, oils and fats, surfactants, cosmetic ingredients, and ultraviolet absorbers. Thickeners, pigments, preservatives, fragrances and the like can be used.

[0025]

EXAMPLES Next, the present invention will be described in more detail with reference to Reference Examples, Test Examples and Examples, but the present invention is not limited thereto.

Reference Example 1 Production of grape extract: 30% by weight of 20 parts by weight of grape seeds
80 parts by weight of (v / v) ethanol was added, and the mixture was extracted at room temperature for 2 weeks with occasional stirring and filtered to obtain a crude extract. This is concentrated under reduced pressure to 1/10 volume, 5 times volume of ethanol is added to the concentrated solution, and filtered. The filtrate was concentrated under reduced pressure, subjected to ultrafiltration, and the resulting liquid was freeze-dried to obtain a grape extract (38% proanthocyanidin in terms of flavanol).
Included).

Reference Example 2 Production of grape extract: 90 parts by weight of water was added to 10 parts by weight of squeezed lees of grape fruits, and the mixture was extracted for 2 hours at 70 to 80 ° C. with occasional stirring. Then, this was filtered to obtain a grape extract [dry solid content: 1.5% (W / V), proanthocyanidin content in flavanol conversion: 8.2% (per dry solid content)].

Reference Example 3 Production of grape extract: 50% by weight per 10 parts by weight of grape seeds
(V / v) 90 parts by weight of 1,3-butylene glycol aqueous solution was added, and the mixture was extracted at 40 ° C. overnight. This was then filtered to give a grape extract [0.58% dry solids (W /
V), proanthocyanidins 48 in flavanol conversion
% (Per dry solid content)].

Test Example 1 Superoxide removing activity measurement test: The grape extract obtained in Reference Example 1 and the active oxygen removing agent shown in Table 1 were used alone or as a mixture to prepare a sample, which was diluted with water and then measured as follows. The superoxide removing activity was measured by the method. That is, 0.05M sodium carbonate buffer (pH 10.2)
2.4 ml of substrate solution [3.0 mM xanthine (0.05
Dissolved in M sodium carbonate buffer)] 0.1 ml, 3.0 m
0.1 ml of M EDTA, 0.1 ml of 0.15% (W / V) bovine serum albumin, 0.1 ml of 0.75 mM nitrobull-tetrazolium and 0.1 ml of each test sample were mixed, and the mixture was allowed to stand at 25 ° C. for 10 minutes. Then, the enzyme solution [xanthine oxidase solution (about 0.04 u with purified water
nits / ml dilution)] 0.1 ml was added to start the reaction, and 25
After incubating at ℃ for 20 minutes, 6 mM CaCl ₂
The reaction is stopped by adding 0.1 ml. Then 560 nm
Absorbance (A) is measured.

The absorbance (B) of the sample to which purified water was added instead of the test sample was used as a control, and 6 was used as the blank of each sample.
After stopping the reaction by adding 0.1 ml of mM CaCl _2, the absorbance (C) of the sample to which 0.1 ml of xanthine oxidase was added was measured, and the superoxide removal rate was calculated from the following formula. The results are shown in Table 1.

[0031] A: Absorbance of sample by enzyme reaction B: Absorbance of control enzyme reaction C: Absorbance of sample without enzyme reaction

Table 1 ────────────────────────────────── Grape extract S O D ^* Augon extract ^{* *} Removal rate Sample (Sample 0.1 ml (Sample 0.1 ml (Sample 0.1 ml (%) Weight μg) Weight μg) Weight μg) ──────────── ─────────────────────── 1 1.0 − − 10.9 2 3.0 − − 22.3 3 10.0 − − 61.5 4-0.01-16.25-0.015-27.9 6-0.02-42.1 7-1.0 18.5 8-3-4.0 34.7 9--10. 0 58.9 10 1.0 0.01-60.0 11 11 0.02-84.5 12 3.0 3.0 0.015-88.0 13 10.0 0.015-157.3 3141 .0-1.0 52.2 15 1.0-3.0 79.0 1 3.0-3.0 85.6 ────────────────────────────────── * * Sigma; cattle Obtained from red blood cells (3.570 units /
mg) ** Made by Ichimaru Falcos

As is clear from the results of Table 1, proanthocyanidins alone had an SOD-like action, but S
It was shown that the combined use with the OD and Scutellariae extract exerts a synergistic effect and is extremely effective in removing active oxygen.

This means that the external preparation for skin of the present invention in which a proanthocyanidin and an active oxygen scavenger are used in combination produces lipid peroxide, inflammation, blackening and aging due to active oxygen production in the skin by ultraviolet rays. On the other hand, it shows that it has an extremely high preventive effect.

Example 1 Emulsion: An emulsion was prepared according to the composition shown in Table 2 and the following production method, and its skin beautifying effect and skin aging preventing effect were examined. The results are shown in Table 3.

(Composition) Table 2 ──────────────────────────────────── Comparative product of the present invention Component (%) ───── ───────────── 1 1 2 3 ──────────────────────── ──────────── (1) Squalane 5.0 5.0 5.0 5.0 5.0 (2) Vaseline 2.0 2.0 2.0 2.0 (3) Beeswax 0.0. 5 0.5 0.5 0.5 (4) sorbitan sesqui 0.8 0.8 0.8 0.8 oleate (5) polyoxyethylene 1.2 1.2 1.2 1.2 1.2 oleyl ether (20E.O.) (6) 1,3-butylene 5.0 5.0 5.0 5.0 5.0 glycol (7) Grape extract ^* 0.1 0.1- (8) dl-α-tocopherol ^** 0.01 - 0.01 - (9) ethyl alcohol 5.0 5.0 5.0 5.0 (10) anti-rot agent 0.2 0.2 0.2 .2 (11) Fragrance 0.1 0.1 0.1 0.1 0.1 (12) Xanthan gum 20.0 20.0 20.0 20.0 (2% aqueous solution) (13) Residual amount of purified water Residual amount Residual amount Residual amount ─────────────────────────────────── * * Manufactured in Reference Example 1 ** Sum Kojunyaku Co., Ltd.

(Production Method) A. Components (6), (7), (9) and (13) were mixed by heating to give 7
Keep at 0 ° C. B. The components (1) to (5), (8) and (10) are heated and mixed,
Keep at 0 ° C. C. The above B was added to the above A and mixed, the component (12) was added to uniformly emulsify, the mixture was cooled to 30 ° C., the component (11) was added and uniformly mixed to obtain an emulsion.

(Testing method) Female 1 aged 28 to 58
A panel of 5 people was applied to the face with an appropriate amount of the test emulsion after washing the face twice a day, morning and night, for 12 weeks. The beautiful skin and anti-aging effect of the application were evaluated according to the following criteria.

Skin beautifying effect: [Evaluation] [Content] Effectiveness The dullness of the skin became inconspicuous. Somewhat effective The dullness of the skin became less noticeable. Ineffective No change from before use.

Skin Aging Preventive Effect: [Evaluation] [Content] Effectiveness The skin's firmness and gloss were improved. Slightly effective Skin tone and gloss were slightly improved. Ineffective No change from before use.

(Result) Table 3 ─────────────────────────────────── Beautiful skin effect Skin aging prevention Efficacy Test emulsion ──────────── ───────────── Effective Fair Effective Ineffective Effective Fair Effective Ineffective ────────── ──────────────────────── PRODUCT OF THE INVENTION 1 13 1 1 1 13 20 0 ──────────────── ────────────────── Comparative product 1 1 9 5 2 6 7 2 3 5 5 7 1 4 10 3 0 2 13 0 1 14 ───────── ────────────────────────── From Table 3, it can be seen that the product of the present invention has remarkable skin beautifying effect and skin aging preventing effect.

Example 2 Cream: A cream was prepared by the composition shown in Table 4 and the following production method, and its skin beautifying effect and skin aging preventing effect were examined. The results are shown in Table 5.

(Composition) Table 4 ───────────────────────────────────── Comparison of the product of the present invention Component (%) ────── ─────────────── 2 3 4 5 6 7 ───────────────── ─────────────────── (1) Beeswax 6.0 6.0 6.0 6.0 6.0 6.0 6.0 (2) Cetanol 5.0 5. 0 5.0 5.0 5.0 5.0 (3) Reduced lanolin 5.0 5.0 5.0 5.0 5.0 5.0 5.0 (4) Squalane 30.0 30.0 30.0 30 .0 30.0 30.0 (5) Glycerin 4.0 4.0 4.0 4.0 4.0 4.0 4.0 Monostearate (6) Lipophilic monostea 2.0 2.0 2.0 2 .0 2.0 2.0 Glycerine phosphate (7) Polyoxyethylene sorbitan monora 2.0 2.0 2.0 2.0 2.0 2.0 Ethyl urate Ether (20 EO) (8) grape extract ^* 0.01 0.01 0.01 - - - (9) ascorbic acid phosphoric acid ester 1.0 - - 1.0 - - Magnesium ^** (10) beta - 0.01--0. ^01- Carotene ^*** (11) Preservative 0.2 0.2 0.2 0.2 0.2 0.2 (12) Fragrance 0.05 0.05 0.05. 05 0.05 0.05 0.05 (13) Purified water Remaining amount Remaining amount Remaining amount Remaining amount Remaining amount ─────────────────────── ────────────── * * Product manufactured in Reference Example 2 ** Made by Nikko Chemicals *** Made by Wako Pure Chemical Industries

(Production Method) A. Components (1) to (7), (11) and (12) are mixed and heated to 70 ° C. B. Components (8) and (13) are mixed and heated to 70 ° C. C. B was added to A, mixed, cooled, (9) and (10) were added, and the mixture was mixed uniformly to obtain a cream. (Test method) Same as Example 1 (evaluation standard) 〃

(Results) Table 5 ──────────────────────────────────── Beautiful skin Effectiveness Skin Anti-aging effect Test cream ──────────── ──────────── Effective slightly effective Not effective Effective slightly effective Not effective ───────── ─────────────────────────── Inventive product 2 11 4 0 11 3 3 1 3 12 3 0 11 11 4 0 ────── ──────────────────────────── Comparative products 4 3 5 7 7 2 6 7 5 6 6 3 6 4 5 6 6 6 4 6 5 3 8 4 7 4 11 0 3 12 ──────────────────────────────────── From the results in Table 5 As is apparent, the creams of the products 2 and 3 of the present invention mourn the "shiny" and "harri" of the skin. , Prevention of aging of the skin such as "dull", was effective in the improvement.

Example 3 Cosmetic water: (treatment) (%) (1) glycerin 5.0 (2) 1,3-butylene glycol 6.5 (3) polyoxyethylene sorbitan 1.2 monolaurate (20E.O.) (4) Ethyl alcohol 8.0 (5) Grape extract ^* 1.0 (6) SOD ^** 0.5 (7) Preservative proper amount (8) Perfume proper amount (9 ) Residual amount of purified water * Produced in Reference Example 3. ** Sigma; obtained from human red blood cells (5.230 units /
mg)

(Production Method) A. Components (3), (4), (7) and (8) are mixed and dissolved. B. Components (1), (2), (5), (6) and (9) are mixed and dissolved. C. A and B were mixed and homogenized to obtain a lotion.

Example 4 Pack: (Method) (%) (1) Polyvinyl alcohol 20.0 (2) Ethyl alcohol 20.0 (3) Glycerin 5.0 (4) Kaolin 6.0 (5) ) Grape extract ^* 0.05 (6) Scutellaria extract ^** 0.2 (7) Preservative 0.2 (8) Perfume 0.1 (9) Refined water balance * Produced in Reference Example 1 Made ** Made by Ichimaru Falcos

(Production Method) A. Components (1), (3) to (5) and (9) are mixed, heated to 70 ° C. and stirred. B. Mix components (2), (7) and (8). C. Add the above B to the above A, mix and cool (6)
Were uniformly dispersed to obtain a pack.

Example 5 Cleaning agent: (treatment) (%) (1) stearic acid 10.0 (2) palmitic acid 8.0 (3) myristic acid 12.0 (4) lauric acid 4.0 (5) Oleyl alcohol 1.5 (6) Purified lanolin 1.0 (7) Perfume 0.1 (8) Preservative 0.2 (9) Glycerin 18.0 (10) Potassium hydroxide 6.0 ( 11) Grape extract ^* 0.5 (12) Acetic acid-dl-α-0.05 tocopherol ^** (13) Purified water residual amount * Produced in Reference Example 3 ** Produced by Sigma

(Production Method) A. Components (9), (10) and (13) are mixed and heated to 70 ° C. B. Ingredients (1) to (6), (8) and (12) were mixed and the mixture was heated to 70 ° C.
Heat to. C. The above B was added to the above A, kept at 70 ° C. for a while, cooled to 50 ° C. after completion of the saponification reaction, and the components (7) and
(11) was added and cooled to obtain a cleaning agent.

Example 6 Gel Ointment: (Method) (%) (1) Carboxyvinyl Polymer 1.0 (2) Triethanolamine 1.0 (3) 1,3-Butylene Glycol 10.0 ( 4) Grape extract ^* 0.01 (5) Ergocalciferol ^** 0.02 (6) Purified water balance * Manufactured in Reference Example 2 ** Manufactured by Sigma

(Production Method) A. Components (1) and (3) to (6) are mixed and dissolved. Component (2) was added to B.A and mixed to homogenize to obtain a gel ointment.

[0054]

The external preparation for skin of the present invention has an excellent action of removing active oxygen, and is stable and excellent in improving skin roughness and preventing skin aging. Therefore, the external preparation for skin of the present invention has an extremely high preventive effect against the generation of lipid peroxide, irritation, blackening, aging, etc. due to the generation of active oxygen in the skin by ultraviolet rays, and it has beauty and medical treatment. It is extremely useful in. that's all

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Reference number within the agency FI Technical indication location // A61K 35/78 C 7822-4C 45/00 8415-4C (72) Inventor Toshiaki Ariga Chiba Prefecture No. 339, Noda, Kikkoman Corporation (72) Inventor, Katsumi Yuasa, No. 339, Noda, Chiba Prefecture, Kikkoman Corporation

Claims (2)

[Claims] 1. An external preparation for skin comprising a proanthocyanidin and an active oxygen scavenger and / or an antioxidant as active ingredients. 2. The external preparation for skin according to claim 1, wherein the proanthocyanidin is contained in the grape extract.