JPH06336422A - External agent for skin - Google Patents

Abstract

PURPOSE:To obtain an external agent for skin, effective for the prevention of skin aging, amelioration of wound, chaps, cracks, sore, piles, scald, etc., heal promotion of wound, etc., owing to its high stability and excellent cell- activation action and extremely useful for beauty and medical care. CONSTITUTION:This external agent for skin such as cosmetics and pharmaceuticals contains proanthocyanidin existing in grape extract, etc., in combination with a cell activation agent as active components.

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 cell activating action, which is effective for preventing skin aging, improving external damage, cracks, cracks and promoting wound healing. , Skin external preparations such as pharmaceuticals.

[0002]

2. Description of the Related Art A skin external preparation for the purpose of activating cells or treating wounds, that is, for the purpose of activating metabolism and preventing skin aging, or for treating wounds and treating wounds after shaving, cracks, cracks, sores. As a medicinal component of the external preparation for skin used for improving hemorrhoids, burns, etc., allantoin and its derivatives, bovine blood deproteinization, shikon extract, aloe extract, carrot extract, placenta extract, etc. are generally used. Came.

[0003]

However, the skin aging preventive action and the wound healing promoting action of the external preparation for skin containing these medicinal components are not always sufficiently satisfactory, and therefore, more excellent cell activation is obtained. It has been desired to develop a skin external preparation having an action.

[0004]

[Problems to be Solved by the Invention]
The present inventors have conducted intensive studies to obtain an external preparation for skin having an excellent cell activating effect, and as a result, it is contained in grape extracts and the like and has an active oxygen removing action [J. Agric. Food Chem., 39: 154
9-1552 (1991)], antioxidant action [JP-A-61-1698]
No. 2, Monthly Food Distribution Technology, 21 (2): 16-19], we found that the combined use of proanthocyanidins with cell activating components synergistically increases the action of the cell activating components. The present invention has been completed.

That is, the present invention provides an external preparation for skin which comprises proanthocyanidins and a cell activating agent as active ingredients.

[0006] Proanthocyanidin, which is an active ingredient of the present invention, is applied to the squeezed lees or seeds of grape fruits, torch shells, vines, bark, adzuki beans, bark of pine, oak, and peaches. 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 of the above-mentioned dimers to 10-mers of the above-mentioned constitutional units, proanthocyanidins such as high molecular weight procyanidins, prodelphinidins and propelargonidins and stereoisomers thereof. Of these, the following formula with excellent solubility etc.

[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 be used.

[0010] 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.

A method for extracting a grape extract containing proanthocyanidins is not particularly limited, and raw materials such as squeezed lees of grape fruits or seeds are 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 cosmetic composition of the present invention is preferably 0,0 in terms of flavanols.
00001-5% by weight (hereinafter referred to simply as "%") (preferably 0.0001-as dry solids of grape extract)
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.

When the content of proanthocyanidin as an active ingredient is less than 0.0001%, a sufficient effect may not be obtained, and when the content exceeds 5%, the effect is further increased. I can't.

On the other hand, examples of the cell activating agent which is another essential component of the present invention include, for example, deoxyribonucleic acid and salts thereof, adenylic acid derivatives such as adenosine triphosphate and adenosine monophosphate and salts thereof, ribonucleic acid and the same. Nucleic acid-related substances such as salts, guanine, xanthine and their derivatives and salts thereof; animal-derived extracts such as serum deproteinization extract, spleen extract, placenta extract, chicken cob extract and royal jelly; yeast extract, Extracts derived from microorganisms such as lactic acid bacterium extract, bifidobacteria extract, and Reishi extract.
Extracts derived from plants such as carrot extract, assembly extract, rosemary extract, oat extract, garlic extract, hinokitiol and cepharanthin; α- or γ-linoleic acid, eicosapentaenoic acid and their derivatives, succinic acid And derivatives thereof and salts thereof, estradiol and derivatives thereof and salts thereof, and the like.

Of these, deoxyribonucleic acid and salts thereof, adenosine triphosphate and salts thereof, serum deproteinization extract, placenta extract, yeast extract, carrot extract, succinic acid and derivatives thereof and salts thereof are preferred. . These cell activators can be used alone or in combination of two or more.

From the viewpoint of stability over time, it is preferable to add 0.001 to 5%, especially 0.01 to 3%, to the external preparation for skin.

The external preparation for skin of the present invention can be prepared by blending the essential components proanthocyanidin and the cell activating agent with various forms of bases known as ordinary 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, foundations, hair cosmetics and detergents.
It may be a dispersion, an ointment, a cream, a drug such as a liquid for external use, a quasi drug, or the like.

The base of the external preparation may be a base suitable for the form of these external preparations, for example, aqueous components, powders, surfactants, oils, humectants, lower alcohols and the like used in ordinary skin external preparations. If necessary, alcohols such as polyhydric alcohols, pH adjusters, preservatives, dyes, antioxidants, ultraviolet absorbers, thickeners, fragrances, beauty ingredients, etc. can be added.

[0022]

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: Purified water is added to 10 parts by weight of crushed grape seeds, extracted at 60 to 70 ° C. for 5 hours, and then filtered. This was concentrated under reduced pressure to 1/10 volume, 5 times volume of ethanol was added to the obtained solution, filtered again, ethanol of the filtrate was distilled off under reduced pressure, ultrafiltration was performed, and the obtained solution was freeze-dried. To obtain a grape extract [containing 36% proanthocyanidin in terms of flavanols].

Reference Example 2 Manufacture of grape extract: 50% by weight of 20% by weight of grape juice meal
80 parts by weight of (v / v) ethanol was added, and the mixture was extracted at room temperature for 10 days and then filtered to obtain a grape extract [0.33% (w / v) as dry solid content, flavanol as proanthocyanidins. Contained 64% (per dry solid content)].

Reference Example 3 Production of Grape Extract: 20 parts by weight of crushed grape seed,
Add 80 parts by weight of 80% (v / v) ethanol, and add 3 at room temperature.
After extracting for a day, it was filtered and dried under reduced pressure to obtain a grape extract [66% of proanthocyanidin in terms of flavanols.
(Per dry solid content) included].

Test Example 1 Wound healing test: Male Wistar rats aged 8 weeks were used as an experiment in groups of 10 rats. After shaving the back of the rat, under anesthesia, two back skins on the left and right were incised over 4 cm so as to be symmetrical with respect to the midline, and one was used as a drug application site and the other was used as a control site. Immediately after the incision, both incised sites were sutured and wiped with ethanol for disinfection. One of the samples shown in Table 1 (dissolved in physiological saline) was applied to the drug application site of the sutured portion, and 0.1 ml of physiological saline was applied to the control site twice a day. It was applied for one week. One week later, the dorsal skin was peeled off to make a strip-shaped section around the incision, and the tensile strength of the skin section was measured with a rheometer NRM-2002J.
(Manufactured by Fudo Kogyo Co., Ltd.). The wound healing rate was calculated from the obtained measured value by the following formula. The results are shown in Table 1.

[0027]

[0028]

* 1 Obtained in Reference Example 1. * 2 Wako Pure Chemical Industries * 3 Sansho Pharmaceutical * 4 Nikko Chemicals

As is clear from Table 1, when the proanthocyanidins were combined with ATP, placenta extract or yeast extract, the wound healing rate was clearly higher than that in the case of using each alone, and synergistically. A significant wound healing promoting effect was observed.

Example 1 Cream: A cream was prepared by 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.

[0032] * 1 Manufactured in Reference Example 1 * 2 Sansho Pharmaceutical * 3 Pentafarm

(Production Method) A. Components (1) to (7), (11) and (12) are mixed and heated to 70 ° C. B. Components (8) to (10) and (13) were mixed and heated to 7
Keep at 0 ° C. C. B was added to A and mixed, and cooled to 30 ° C. to obtain a cream.

(Test Method) Female 4 to 26-52 years old 4
A panel of 5 people was applied to the face with an appropriate amount of each 2 test cream products 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 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 scalp and gloss of the skin were improved. Slightly effective Skin tone and gloss were slightly improved. Ineffective No change from before use.

[0037]

As is clear from the results in Table 3, the creams of the products 1 and 2 of the present invention containing proanthocyanidin and a placenta extract or bovine blood deproteinizing agent are more effective than the creams containing them alone. "Glossy", "Hari"
It exhibited excellent effects in preventing and improving skin loss, skin aging phenomena such as dullness, and improvement.

Example 2 Cosmetic water: (Method) Compounding amount (%) (1) Polyoxyethylene (60 EO) hydrogenated castor oil 1.0 (2) Ethanol 15.0 (3) Preservative 0.1 (4) Hinokitiol 0.01 (5) Perfume proper amount (6) Grape extract ^{* 1} 2.0 (7) Citric acid 0.1 (8) Sodium citrate 0.3 (9) 1,3 -Butylene glycol 4.0 (10) Residual amount of purified water * 1 Prepared in Reference Example 2.

(Production Method) A. Components (1) to (5) are heated and mixed to dissolve. B. Components (6) to (10) are heated and mixed to dissolve. C. A and B were mixed to obtain a lotion.

Example 3 Emulsion: (Method) Compounding amount (%) (1) Polyoxyethylene (10 EO) 1.0 Sorbitan monostearate (2) Polyoxyethylene (60 EO) 0.5 Sorbit tetraoleate (3) Glyceryl monostearate 1.0 (4) Stearic acid 0.5 (5) Behenyl alcohol 0.5 (6) Squalane 8.0 (7) Eicosapentaenoic acid 5.0 (8) ) Preservatives 0.1 (9) Grape extract ^{* 1} 0.1 (10) Carboxyvinyl polymer 0.1 (11) Sodium hydroxide 0.05 (12) Ethyl alcohol 5.0 (13) Purified water Remaining amount (14) Fragrance Suitable amount * 1 Prepared in Reference Example 3.

(Production Method) A. Components (9) to (13) are mixed by heating and kept at 70 ° C. B. Components (1) to (8) are mixed by heating and kept at 70 ° C. C. Add B to A, mix, and uniformly emulsify. After cooling D.C., (14) was added and uniformly mixed to obtain an emulsion.

Example 4 Ointment: (Method) Compounding amount (%) (1) Stearic acid 18.0 (2) Cetanol 4.0 (3) Triethanolamine 2.0 (4) Glycerin 5.0 (5) Grape extract ^{* 1} 1.0 (6) Succinic acid ^{* 2} 1.0 (7) Residual amount of purified water * 1 Prepared in Reference Example 2 * 2 Wako Pure Chemical Industries

(Production Method) A. A part of the components (3), (4) and (7) was heated and mixed, and 75
Keep at ℃. B. Heat mix components (1) and (2) and keep at 75 ° C. C. Add A slowly to B. While cooling DC, (5) and (6) dissolved in the rest of (7) were added to obtain an ointment.

[0045]

Since the external preparation for skin of the present invention has an excellent cell activating effect, it is effective for preventing skin aging, improving wounds, cracks, cracks, sores, hemorrhoids, burns, promoting wound healing and the like. , Is extremely useful in beauty and medicine. that's all

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Office reference number FI technical display location A61K 31/35 ADA 9454-4C 31/70 9454-4C 35/78 C 7822-4C 45/00 ADT 8415-4C // (A61K 31/35 45:00) 8415-4C (A61K 31/35 31:70) 9454-4C (72) Inventor Toshiaki Ariga 339 Noda, Noda City, Chiba Prefecture Kikkoman Corporation (72) Inventor Katsumi Yuasa 339 Noda, Noda City, Chiba Prefecture Kikkoman Corporation

Claims (2)

[Claims] 1. A skin external preparation containing proanthocyanidins and a cell activator as active ingredients. 2. The external preparation for skin according to claim 1, wherein the proanthocyanidin is contained in the grape extract.