JPH06336421A - External agent for skin - Google Patents

Abstract

PURPOSE:To obtain an external agent for skin, exhibiting high suppressing effect on the inflammation of skin caused by sunburn and the pigmentation of the sunburnt skin owing to its high stability and excellent antiinflammatory action and skin-beautifying 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 an antiinflammatory 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 a skin external preparation, and more particularly to a skin external preparation such as cosmetics and pharmaceuticals having excellent skin inflammation-preventing and whitening effects.

[0002]

2. Description of the Related Art Conventionally, agents having an anti-inflammatory effect such as calamine have been used to suppress skin inflammation due to sunburn, and ascorbine has been used to suppress pigmentation after sunburn. Drugs having a whitening effect, such as acid and glutathione, have been used as components of external preparations for skin.

However, it has been difficult to say that the external preparation for skin containing these medicinal components has a weak anti-inflammatory effect and a whitening effect and has a sufficient sunburn preventing effect.

[0004] In addition, proanthocyanidins contained in grape extracts and the like have an active oxygen removing action [J. Agric. Food
Chem., 39: 1549-1552 (1991)], antioxidant action [JP-A-61-16982, Monthly Food Distribution Technology, 21 (2): 16-1
9], and whitening action of procyanidin, which is one of its constituents, (JP-A-2-1343).
09) is known. However, this whitening effect is not always satisfactory.

The present invention has been made for the purpose of providing a skin external preparation having more excellent anti-inflammatory and whitening effects than conventional skin external preparations.

The inventors of the present invention have conducted extensive studies to achieve the above-mentioned object, and as a result, by using proanthocyanidin as an active ingredient in combination with an anti-inflammatory agent applied to a skin external preparation, the skin caused by sunburn The present invention has been completed by finding that a skin external preparation having a synergistic effect of suppressing the above inflammation and pigmentation after sunburn is obtained.

[0007]

Therefore, the present inventors have
In order to obtain a skin external preparation that fully utilizes the effects of proanthocyanidins, as a result of intensive research, by combining a proanthocyanidin and an anti-inflammatory agent applied to the skin external preparation, the above problems have been solved. The inventors have found that a skin external preparation having a synergistic effect of suppressing skin inflammation due to sunburn and pigmentation after sunburn can be obtained, and completed the present invention.

That is, the present invention provides an external preparation for skin, which comprises proanthocyanidins and an anti-inflammatory agent as active ingredients.

Proanthocyanidins, which are the active ingredients of the present invention, are used in the squeezed lees or seeds of grape fruits, as well as the husks of conker, vines, bark, red beans, bark of pine, oak, and peach. It is a compound included.

More specifically, the proanthocyanidins are condensed or polymerized with condensed tannins existing in various plants as described above, that is, flavan-3-ol or flavan-3,4-diol as a constitutional 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 constitutional units, dimers to 10-mers, 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.

Proanthocyanidins are usually contained in the grape extract extracted from 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 extraction method of 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.

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

On the other hand, as an anti-inflammatory agent which is another essential component of the present invention, glycyrrhizic acid, glycyrrhetinic acid, mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene and their derivatives and salts thereof , Ε-
Aminocaproic acid, zinc oxide, sodium diclofenac, licorice extract, aloe extract, shikon extract, salvia extract, arnica extract, chamomile extract, birch extract, hypericum extract, eucalyptus extract, mukuroji extract, etc. Can be mentioned.

Of these anti-inflammatory agents, particularly preferred are glycyrrhizic acid, glycyrrhetinic acid, guaiazulene and derivatives thereof and salts thereof, ε-aminocaproic acid, licorice extract, aloe extract, sardine extract, A chamomile extract is mentioned.

The content of these anti-inflammatory agents in the external preparation for skin of the present invention is generally 0.0001% to 5%, preferably 0.01 to 3%. These anti-inflammatory agents can be used alone or in combination of two or more.

The external preparation for skin of the present invention can be prepared by blending the essential components proanthocyanidin and an anti-inflammatory 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 emulsion, cream, lotion, pack, foundation, hair cosmetic, and cleaning agent.
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, pigments, antioxidants, thickeners, fragrances, beauty ingredients and the like can be added.

[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: 50% by weight per 20 parts by weight of grape seeds
(V / v) Ethanol (80 parts by weight) was added, and the mixture was extracted at room temperature for 5 days with occasional stirring, filtered, and the filtrate was evaporated to dryness under reduced pressure to give a grape extract [54% proanthocyanidin in terms of flavanols. (Per dry solid content) included].

Reference Example 2 Manufacture of Grape Extract: Grinded grape juice dregs 20
80 parts by weight of hot water was added to parts by weight, and the mixture was extracted at 60 to 70 ° C. for 5 hours and then filtered to obtain a grape extract [5.5% dry solids (W / V), proanthocyanidins. Content of 4.5% (per dry solid content) in terms of flavanols].

Reference Example 3 Production of grape extract: 5 parts by weight of crushed grape seeds
90% by weight of 0% (v / v) acetone was added, and the mixture was extracted at room temperature for 7 days with occasional stirring, filtered, and the filtrate was dried under reduced pressure to give a grape extract [proanthocyanidin converted to flavanols. Of 54% (per dry solid content).

Test Example 1 Anti-inflammatory effect and whitening effect: A lotion containing the drugs shown in Table 1 and ethanol 15% (v / v) and the balance being purified water was prepared and applied to the back of colored guinea pigs. The effects of sunburn on inflammation and pigmentation were investigated. The results are shown in Table 2.

(Test method) Colored guinea pigs (10 in each group)
The back of each animal was shaved and irradiated with ultraviolet rays under anesthesia. UV irradiation is performed with Toshiba Corporation FL20S / BLB lamp and F
Three L20S / E30 lamps were simultaneously irradiated, and the amount of ultraviolet rays was 4.8 × 10 ⁶ erg / cm ² . 0.2 ml of the sample was rubbed well into the four places on the back of the guinea pig 24 hours before, immediately after, 12 hours and 24 hours after the irradiation with ultraviolet rays. The application site was thoroughly washed with warm water before irradiation with ultraviolet rays. The degree of inflammation was observed 24 hours after irradiation and the degree of pigmentation 7 days later.

[0031] * 1 Obtained in Reference Example 1. * 2 Maruzen Pharmaceutical Co., Ltd. * 3 Wako Pure Chemical Industries Ltd. * 4 80% (v / v) ethanol 80 per 20 parts by weight of Sikon
Parts by weight were added, and the mixture was extracted at 40 to 50 ° C for 5 hours, filtered, and the filtrate was dried under reduced pressure.

(Evaluation Criteria) Evaluation Criteria for Inflammation (Anti-inflammatory Effect) 0: No inflammation is observed 1: Very slight inflammation is observed 2: Inflammation is observed but the boundary with the non-irradiated site is unclear 3 : Inflammation was observed and the boundary with the non-irradiated area was clear

Evaluation criteria for pigmentation (whitening effect) 0: No pigmentation is observed at all 1: Very slight pigmentation is observed 2: Pigmentation is observed, but the boundary with the non-irradiated site is unclear 3: Pigmentation is observed and the boundary with the non-irradiated area is clear

According to the above evaluation criteria, each score is 1
Count how many out of 10 guinea pigs are below the score,
It judged according to the following judgment criteria.

[0035]

[0036]

From the results shown in Table 2, the lotion of the present invention containing proanthocyanidin and dipotassium glycyrrhizinate, guaiazulene or the extract of shikon has excellent anti-inflammatory effect and whitening effect as compared with the lotion containing them alone. It is clear that

Example 1 Cream: A cream was prepared by the following formulation and the following production method. (Method) Compounding amount (%) (1) Polyoxyethylene monostearate (40E.O.) 2.0 (2) Glyceryl monostearate (self-emulsifying type) 5.0 (3) Stearic acid 5.0 (4) Behenyl alcohol 0.5 (5) Squalane 15.0 (6) Cetyl isooctanoate 5.0 (7) Butylparaben 0.1 (8) Methylparaben 0.1 (9) 1,3-Butylene glycol 5.0 (10) Dipotassium glycyrrhizinate ^{* 1} 0.2 (11) Grape extract ^{* 2} 0.5 (12) Residual amount of purified water (13) Appropriate amount of fragrance * 1 Maruzen Pharmaceuticals * 2 Produced in Reference Example 1 What I did

(Production Method) A. Components (1) to (7) are heated and dissolved at 70 ° C. B. Components (8) to (12) are heated and dissolved at 70 ° C. C. Add A to B and emulsify. Ingredient (13) is added to DC and cooled to obtain a cream.

Example 2 Emulsion: An emulsion was prepared by the following formulation and the following production method. (Method) Compounding amount (%) (1) Polyoxyethylene sorbitan 1.0 Monostearate (10 EO) (2) Polyoxyethylene sorbit 0.5 Tetraoleate (60 EO) (3) Glyceryl monostearate 1.0 (4) Stearic acid 0.5 (5) Behenyl alcohol 0.5 (6) Refined avocado oil 4.0 (7) Glyceryl tri-2-ethylhexanoate 4.0 (8) Butylparaben 0.1 (9) ) Grape extract ^{* 1} 1.0 (10) Guaiazulene 0.2 (11) Methylparaben 0.1 (12) Carboxyvinyl polymer 0.07 (13) 1,3-Butylene glycol 5.0 (14) Purified water Residual amount (15) Sodium hydroxide 0.025 (16) Purified water 7.5 (17) Fragrance Suitable amount * 1 Prepared in Reference Example 2.

(Production Method) A. Components (1) to (10) are heated and dissolved at 70 ° C. B. Components (11) to (14) are heated and dissolved at 70 ° C. . C. Add A to B and emulsify. (15) to (17) are added to DC and cooled to obtain a cream.

Example 3 Chemical lotion: lotion was prepared by the following formulation and the following production method. (Method) Compounding amount (%) (1) Polyoxyethylene hydrogenated castor oil (60E.O) 1.0 (2) Perfume proper amount (3) Ethanol 10.0 (4) Methylparaben 0.1 (5) ε -Aminocaproic acid 0.3 (6) Citric acid 0.1 (7) Sodium citrate 0.3 (8) 1,3-Butylene glycol 5.0 (9) Grape extract ^{* 1} 0.01 (10) Refined Residual water production * 1 Prepared in Reference Example 3.

(Production Method) A. Components (1) to (5) are heated and dissolved at 70 ° C. B. Components (6) to (11) are heated and dissolved at 70 ° C. C. Add B to A and stir to obtain lotion.

[0044]

The external preparation for skin of the present invention is stable and has excellent anti-inflammatory and whitening effects, and therefore exerts a high inhibitory effect on skin inflammation due to sunburn and pigmentation after sunburn, and is effective in beauty and medical treatment. It is extremely useful in. that's all

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical indication location A61K 31/35 ADA 9454-4C 35/78 C 7822-4C 45/06 8415-4C (72) Invention 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 an anti-inflammatory agent as active ingredients. 2. The external preparation for skin according to claim 1, wherein the proanthocyanidin is contained in the grape extract.