JPH0532556A - Skin agent for external use - Google Patents

Abstract

PURPOSE:To obtain an external agent for skin useful for the amelioration of chapped skin and the prevention of the aging of skin by using ginkgo extract and a superoxide dismutase as active components. CONSTITUTION:The objective agent contains, as active components, 0.001-10wt.% (in terms of dried solid) of an extract extracted from the leaf, flower, twig, fruit, etc., of ginkgo tree and 0.00001-5wt.% of a superoxide dismutase which is a superoxide elimination enzyme widely distributed in the body of animal, vegetable, microorganism, etc. The active components are compounded to various bases and used in the form of cosmetics such as milky lotion, cream, face lotion, pack, dispersion and cleansing agent or medicines such as ointment, cream and liquid for external use. It has extremely high preventing effect on the formation of lipid peroxide, inflammation, melanization, aging, etc., caused by the generation of active oxygen in the skin by the action of ultraviolet rays.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin, more specifically, a cosmetic having an excellent effect of removing active oxygen, an effect of preventing lipid peroxidation, an effect of preventing skin aging, an effect of improving rough skin, and the like. The present invention relates to external preparations for skin such as pharmaceuticals.

[0002]

2. Description of the Related Art It is becoming clear that the generation of active oxygen in the skin is greatly involved in the aging of the skin. Therefore, in recent years, for the purpose of preventing skin aging, active oxygen generation inhibitors, active oxygen scavengers, antioxidants and the like have been increasingly applied to external skin preparations.

On the other hand, as the medicinally active ingredient for improving skin roughness and preventing skin aging, allantoin, aloe extract, ginseng extract, placenta extract, bovine blood deproteinate, fermented metabolites and the like are known.

However, an external preparation for skin containing these medicinal components cannot exert a sufficient effect for improving rough skin and preventing skin aging, and it is desired to develop an external preparation for skin having a more excellent cell activating effect. Was there.

In such a situation, the ginkgo extract is
Antioxidant action (Journal of the Pharmaceutical Society of Japan 39 (2), 1097 (198)
7)), active oxygen scavenging action (Life Science 39,2327 (198
6)) has become known.

[0006]

However, when Ginkgo biloba extract is blended alone, the effect 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 of Ginkgo biloba extract originally contained cannot be exerted. further,
There is a limit to the action and effect when a ginkgo biloba extract is mixed at a high concentration for the purpose of obtaining a higher effect, and conversely, due to the generation of a unique color and odor of the ginkgo biloba extract itself, the amount and dosage form, etc. There was also a problem that product restrictions would occur.

[0007]

In view of the above-mentioned circumstances, the inventors of the present invention have conducted earnest studies to fully bring out the skin action effect of the ginkgo biloba extract. And as a result,
By using the ginkgo biloba extract and superoxide dismutase in combination, the effects on skin roughening and skin aging prevention are synergistically exerted, and the original effects of ginkgo biloba extract as a skin external preparation can be stably obtained. It was found that the present invention has been completed.

[0008] That is, the present invention provides an external preparation for skin characterized by containing a ginkgo biloba extract and superoxide dismutase.

The ginkgo biloba extract used as an essential component in the present invention is obtained by extracting from leaves, flowers, branches, fruits, etc. of ginkgo biloba L.

The extraction method of the Ginkgo biloba extract is not particularly limited, and examples thereof include water, primary alcohols such as methyl alcohol and ethyl alcohol, liquid polyhydric alcohols such as propylene glycol and 1,3-butylene glycol, and acetic acid. Lower alkyl ester such as ethyl ester,
A method using a known solvent such as hydrocarbons such as benzene and hexane, ethyl ether, acetone and the like is adopted, and these solvents can be used alone or in combination of two or more kinds. 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.

Ginkgo biloba extracts include ginkgo leaves,
The extract obtained by immersing the raw material of flowers, branches, fruits, etc. in the above extraction solvent, extracting it at room temperature or under heating, and filtering it may be used as it is, but it is further concentrated if necessary. May be used. Also, these extracts can be purified and used.

The content of the ginkgo biloba extract in the external preparation for skin of the present invention is preferably 0.000 as a dry solid content.
The content is 1 to 10% by weight (hereinafter simply referred to as "%"), and more preferably 0.01 to 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.

Content of ginkgo biloba extract is 0.0001%
If the amount is less than the above, sufficient effect may not be obtained, and even if the amount exceeds 10%, no further increase in the effect is observed. Instead, coloring, odor generation, or precipitation depending on the dosage form may occur. There may be a problem in product such as occurrence.

On the other hand, superoxide dismutase (hereinafter referred to as "SOD"), which is another essential component of the present invention, is a superoxide scavenging enzyme widely distributed in the living body of animals, plants, microorganisms and the like, and its origin and The acquisition method is not particularly limited.

As a method for producing this SOD, humans,
Even if extracted from animal tissues such as cows and dogs, cabbage,
It may be one extracted from plants such as cucumber and lettuce, one extracted from microorganisms, or one produced by genetic engineering. Further, if SOD is the main component, it does not necessarily have to be purified.

The content of these SODs in the external preparation for skin of the present invention is generally 0.0001% to 5%, preferably 0.001%.
001 to 3%. SOD content is 0.00011
If it is less than 5%, a sufficient effect may not be obtained, and even if it exceeds 5%, the effect may not be further increased, and the formulation may be adversely affected.

The external preparation for skin of the present invention can be prepared by blending the essential components Ginkgo biloba extract and SOD with various forms of bases known as conventional external preparations for skin according to a conventional method.

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 alcohols, polyhydric alcohols, oils and fats, surfactants, cosmetic ingredients, and ultraviolet absorbers. Thickeners, pigments, preservatives, perfumes and the like can be used.

[0019]

EXAMPLES Next, the present invention will be described in more detail with reference to test examples and examples, but the present invention is not limited to these.

Test Example 1 Superoxide removal activity measurement test: To 20 parts by weight of dried ginkgo leaves, 80 parts by weight of 50V / V% ethyl alcohol was added, and the mixture was extracted for 3 days at room temperature with occasional stirring, and filtered to extract ginkgo biloba. A liquid was obtained. Using this as a sample, the superoxide removing activity was measured by the following measuring method.
In addition, the activity was also measured for commercially available SOD and a combination thereof with a Ginkgo biloba extract.
The results are shown in Table 1.

(Measurement method) A substrate solution [3.0 m] was added to 2.4 ml of 0.05 M sodium carbonate buffer (pH 10.2).
M xanthine (dissolved in 0.05M sodium carbonate buffer)] 0.1 ml, 3.0 mM EDTA 0.1 ml, 0.1.
15% (W / V) bovine serum albumin, 0.75 mM nitroblu-tetrazolium 0.1 ml and 0.1 ml of each sample
After mixing for 10 minutes at 25 ° C, the enzyme solution [xanthine oxidase solution (about 0.04 units with purified water
/ ml dilution)] 0.1 ml is added to start the reaction. 25
After incubating at 0 ° C for 20 minutes, 6 mM CaCl ₂
The reaction is stopped by adding 0.1 ml. Then 560 nm
Absorbance (A) is measured.

As a control, the absorbance (B) of the sample to which purified water was added instead of the sample, and as a blank of each sample, 6 mM was used.
After the reaction was stopped by adding 0.1 ml of 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. A: Absorbance of sample by enzyme reaction B: Absorbance of control enzyme reaction C: Absorbance of sample without enzyme reaction

Table 1 ────────────────────────────────── Ginkgo biloba extract ^* S O D ^** removed Rate Sample (volume% in 0.1 ml sample) (weight μg in 0.1 ml sample) (%) ─────────────────────────── ──────── 1 1.0 -12.3 2 2.0 24.7 3 5.0 -57.5 4 -0.01 17.9 5 -0.015 29.5 6- 0.02 43.3 7 1.0 0.01 55.2 8 1.0 0.02 80.3 9 2.0 0.015 74.8 10 5.0 5.0 0.015 98.0 ──── ────────────────────────────── * Add 50 parts of 50V / V% ethyl alcohol aqueous solution to 10 parts of ginkgo leaves at room temperature. Extracted for 3 days and then filtered. Includes about 4.5% as solid content. ** Sigma; obtained from bovine red blood cells; 3.570 units
/ mg

As is clear from the results shown in Table 1, Ginkgo biloba extract had an SOD-like action even when used alone, but when used in combination with SOD, it exerts a synergistic action and is extremely effective in removing active oxygen. It was shown to be.

This means that the external preparation for skin of the present invention in which the ginkgo biloba extract and SOD are used in combination is effective against the production of lipid peroxide, inflammation, blackening and aging due to the production of active oxygen in the skin by ultraviolet rays. This 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) Ginkgo biloba extract ^* 0.1 0.1 --- (8) Superoxide 0.01 -0.01-Dismutase ^** (9) Ethyl alcohol 5.0 5.0 5.0 5.0 5.0 (10) Preservatives 0.0. 2 0.2 0.2 0.2 (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 ) Purified water Residual amount Residual amount Residual amount ─────────────────────────────────── * Ginkgo leaves 50 parts of 50 V / V% ethyl alcohol aqueous solution was added to 10 parts, extracted at room temperature for 3 days, and then filtered. Includes about 4.5% as solid content. ** Sigma; obtained from bovine erythrocytes; 3.570 uni
ts / mg

(Production Method) A. Components (6), (7), (9) and (13) were mixed by heating to give 7
Keep at 0 ° C. B. Components (1) to (5) and (10) are mixed by heating and kept at 70 ° 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 components (8) and (11) were added, and the mixture was uniformly mixed to obtain an emulsion. To get

(Test method) Female aged 28 to 58 1
A panel of 5 people was applied to the face with an appropriate amount of the test emulsion after washing the face twice daily in the morning and at 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 Dullness of the skin became inconspicuous. Somewhat effective The dullness of the skin has become less noticeable. No effect No change from before use.

Skin Aging Preventive Effect: [Evaluation] [Content] Effectiveness The scalp and gloss of the skin were improved. Slightly effective Skin tone and gloss were slightly improved. No effect No change from before use.

(Result) Table 3 ─────────────────────────────────── Beautiful skin effect Skin aging prevention Efficacy Test emulsion ──────────── ───────────── Effective Effective Effective Effective Effective Effective Effective Effective Ineffective ────────── ──────────────────────── Product of the present invention 1 13 1 1 13 2 20 ──────────────── ────────────────── Comparison products 1 5 6 4 3 8 4 4 2 6 6 3 5 5 5 5 3 0 3 3 12 0 2 13 ──────── ───────────────────────────

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 0.0 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) Ginkgo extract ^{* 0.01 0.01 0.01 - - - (} 9) SOD -containing plastics 1.0 - - 1.0 - - Center Extract ^** (10) from Cabbage - 0.2 − − 0.2 − SOD ^*** (11) Preservatives 0.2 0.2 0.2 0.2 0.2 0.2 (12) Fragrances 0.05 0.05 0.05. 05 0.05 0.05 0.05 (13) Purified water Residual amount Residual amount Residual amount Residual amount Residual amount ─────────────────────── ────────────── * 90 parts of 90V / V% ethyl alcohol aqueous solution was added to 10 parts of ginkgo biloba leaves, extracted at 60 ° C for 3 hours, filtered and dried under reduced pressure ** 10 kg of bovine placenta is cut into small pieces, a double amount of 5% V / V ethyl alcohol aqueous solution is added, and the mixture is extracted at 37 ° C for 6 hours, and then purified by gel filtration, dialysis and the like. (Yield about 2K
g) Protein amount about 1.0-1.5% *** 1Kg cabbage is cut into small pieces, and the same amount of purified water is added to homogenize. Ammonium sulfate fractionation after filtration and dialysis treatment. (Yield about 10g) Protein amount about 2.0-4.0%

(Production Method) A. Components (1) to (7), (11) and (12) are mixed and heated to 70 ° C. B. Ingredients (8) and (13) are mixed and heated to 70 ° C. C. B was added to A, and after mixing, the mixture was cooled, (9) and (10) were added, and the mixture was uniformly mixed 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 14 1 0 11 4 0 3 3 12 3 0 13 1 1 1 ────── ──────────────────────────── Comparative product 4 5 6 4 3 3 7 5 5 5 4 4 6 2 9 4 6 3 3 9 3 6 2 7 7 0 2 13 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 "gloss" and "comfort" 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) Ginkgo biloba extract ^* 1.0 (6) SOD ^** 0.5 (7) Preservative proper amount (8) Perfume proper amount (9 ) Residual amount of purified water * 90 parts of 50V / V% 1,3-butylene glycol aqueous solution was added to 10 parts of ginkgo leaves, extracted at 40 ° C overnight, and obtained by filtration. ** 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) ) Ginkgo biloba extract ^* 0.05 (6) Placenta extract containing SOD ^** 0.01 (7) Antiseptic 0.2 (8) Perfume 0.1 (9) Residual amount of purified water * In Example 1 Same ** Example 2 freeze-dried

(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) Ginkgo biloba extract ^* 0.5 (12) SOD ^** 0.05 (13) Purified water balance * Same as Example 3 ** Made by Sigma; obtained from Horseradish; 2.1
50 units / mg.

(Production Method) A. Components (9), (10) and (13) are mixed and heated to 70 ° C. B. Components (1)-(6) and (8) are mixed and heated to 70 ° C. C. The above B was added to the above A, kept at 70 ° C. for a while, cooled to 50 ° C. after the saponification reaction was completed, and the components (7), (1
1) and (12) were 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) Ginkgo biloba extract ^* 0.01 (5) SOD ^** 0.02 (6) Purified water balance * Same as Example 2 ** Same as Example 3

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

[0045]

EFFECT OF THE INVENTION Since the external preparation for skin of the present invention has an excellent action of removing active oxygen, it has a stable and excellent effect in improving rough skin and preventing skin aging. Therefore, the external preparation for skin of the present invention has an extremely high preventive effect against lipid peroxide generation, inflammation, blackening, aging, etc. due to 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

Claims (1)

Claim: What is claimed is: 1. An external preparation for skin, comprising a ginkgo biloba extract and superoxide dismutase.