JPH11322569A - Composition for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition for external use for skin that has excellent skin-whitening action by using a specific ellagic acid compound and an extract of the whole grass of Leonurus sibiricus or the like. SOLUTION: This composition comprises (A) 0.05-10 wt.% of at least one selected from ellagic acid compounds of formula I (R1 -R4 are each H, a 1-20C alkyl, a saccharide residue of formula II or the like; R5 is H, OH, a 1-8C alkoxy) and their alkali metal salts, for example, ellagic acid, 3,4-di-o-methylellagic acid or the like) and (B) at least one selected from extracts of the following plants: whole grass of Leonurus sibiricus, Lamium album, Visci herba, Prunellae spica, root of Angelica acutiloba, Achyranthis radix, Artemisiae argyi folium, leaf of Uncaria gambir, Calluna vulgaris, Arthemisia japonica THUNG., Centella asiatica, Momordicae semen, rhizome of Alocasia odora, Japanese linden, Tilia japonica, Isodonis herba, Angelica utilis and Dipsacus japonicus. The concentration ratio of the component A to the component B is preferably 1:20 to 50:1 by weight. Oil componens, water, surfactants and the like can be formulated to this composition.

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, peroxides such as hydrogen peroxide, zinc peroxide and magnesium peroxide, ascorbic acid, glutathione, colloidal sulfur and various natural products have been used. Attempts have been made to use whitening cosmetics as active ingredients. 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.

[0004] On the other hand, in the United States and the like, hydroquinone is used as a skin bleaching agent. This hydroquinone is irritating and allergic. There's a problem.

Therefore, various studies have been conducted to develop cosmetics having a skin whitening effect without such disadvantages. A skin whitening external preparation using kojic acid and a kojic acid derivative (Japanese Patent Application Laid-Open JP-A-53-3538, JP-B-56
Nos. 18569, 58-22151 and 6
Nos. 0-9722 and 61-60801), cosmetics containing quercetin as an active ingredient (JP-A-55-92).
No. 305), cosmetics containing quercetin fatty acid ester as an active ingredient (Japanese Patent Application Laid-Open No. 58-131911), and cosmetics using catechin or the like as an active ingredient (Japanese Patent Application Laid-Open No. Sho 5).
2-44375) and the like. 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 There are problems such as
It is not always satisfactory.

Accordingly, the present inventors have overcome the drawbacks of the conventional skin external preparations for whitening, have excellent skin whitening effects, are highly safe, and have improved stability and odor. For the purpose of providing a skin external preparation without problems, as a result of diligent search for those that suppress tyrosinase activity, which plays the most important role in the production of melanin pigments, those with a polyphenol skeleton, especially ellagic acid compounds and their alkalis It has been found that metal salts are excellent (Patent Registration No. 1839986).

[0007] As a result of further studies, the present inventors have found that
Even when the particularly excellent ellagic acid-based compound or its alkali metal salt is blended in a cosmetic or quasi-drug base, the skin whitening effect is not always sufficient at the concentration of the usual external preparation. I understood.

[0008]

DISCLOSURE OF THE INVENTION In view of the above circumstances, the inventors of the present invention have conducted repeated studies for the purpose of improving the skin whitening effect of a preparation containing the above ellagic acid compound or an alkali metal salt thereof. , With such substances,
The present inventors have found that the whitening effect is remarkably improved by coexistence with at least one selected from plant extracts such as botanical extract, quince, sycamore, and bonito, thereby completing the present invention.

[0009]

According to the present invention, (A)
The following general formula (1)

Embedded image (In the formula, R ₁ , R ₂ , R ₃ and R ₄ represent a hydrogen atom and a carbon atom of 1 to 1.
An alkyl group of 20; an acyl group having 1 to 20 carbon atoms;
(CmH ₂ m-O) nH (where m is 2 or 3 and n is 1
Or a (poly) oxyalkylene group represented by the following formula:

Embedded image Which may be the same or different, and R ₅ represents a hydrogen atom, a hydroxyl group or an alkoxy group having 1 to 8 carbon atoms. (B) at least one compound selected from the ellagic acid compounds and alkali metal salts thereof represented by the following formulas: (B) Yakumoso (mass mother plant, mehajiki), odorisou, sukisei (mulberry parasitism, mistletoe or mistletoe or mistletoe), Kakoso (summer hay grass, Nepenthes), Touki (Toki), Gossip (cow knees, Hinata no Kozuchi), Guiyou (Aiba leaves, mugwort or sagebrush or sagebrush), Asenyaku (Asenyaku, Gambir), Erica (Gyorymokudoki), Seikou (Carabid carrot or Artemisia), asiatica, Mokubetsushi, Rhododendron (Marminorushi), linden (Europea japonicus), enmeiso (extended life grass, Hiyoki-ko or Kurobana-hioki-oshi), Ashitaba, Nabena (intermittent or intermittent, Tonabena or Sina) Skin external composition characterized by containing a skin external composition characterized by containing at least one selected from extracts of Na) is provided.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION In the skin external preparation composition of the present invention, the component (A) has the following general formula (1)

Embedded image (In the formula, R ₁ , R ₂ , R ₃ and R ₄ represent a hydrogen atom and a carbon atom of 1 to 1.
An alkyl group of 20; an acyl group having 1 to 20 carbon atoms;
(CmH ₂ m-O) nH (where m is 2 or 3 and n is 1
Or a (poly) oxyalkylene group represented by the following formula:

Embedded image Which may be the same or different, and R ₅ represents a hydrogen atom, a hydroxyl group or an alkoxy group having 1 to 8 carbon atoms. ) And at least one compound selected from the group consisting of ellagic acid compounds and alkali metal salts thereof.

The ellagic acid compound represented by the general formula (1) and the alkali metal salt thereof will be specifically described.
In the general formula (1), when R ₁ , R ₂ , 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. Particularly, a methyl group and an ethyl group are preferable. R ₁ , R ₂ , R
_{When 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. R ₁ , R ₂ , R ₃ , and R ₄ represent-(CmH ₂ m-O)
When it is nH, specific examples thereof include a (poly) oxyethylene group and a (poly) oxypropylene 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,
Examples include a propoxy group, 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 compound of the component A of the composition for external use on the skin of the present invention includes, for example, R in the aforementioned general formula (1).
Ellagic acid in which ₁ , R ₂ , R ₃ , R ₄ and R ₅ are all hydrogen atoms, or 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 is preferably used. 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 R ₁ , R ₂ , Some of R ₃ and R ₄ are a long-chain alkyl group having up to 20 carbon atoms, a long-chain acyl group having up to 20 carbon atoms, a formula-
Selected from a (poly) oxyalkylene group represented by (CmH2m-O-) nH (where m is 2 or 3 and n is an integer of 1 or more) and a sugar residue represented by the above formula ( ₂ ). R ₅ may be substituted with a long-chain alkoxy having up to 8 carbon atoms.

Specific examples of the ellagic acid compound and the alkali metal salt thereof include ellagic acid, 3,4-di-o-methylellagic acid, 3,3'-di-o-methylellagic acid,
3 ′, 4-tri-o-methylellagic acid, 3,3 ′, 4
4'-tetra-o-methyl-5-methoxyellagic acid, 3
-O-ethyl-4-o-methyl-5-hydroxyellagic acid, amritoside (R ₁ : structural formula 2, 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, ammaroku, kyukyuyou, enfuyou, geisha, kakojuyou, oak, kiju, kenjin, kounaka, sankyukon,
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, the dried and pulverized natural product containing the 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 the ellagic acid-based compound as the component A and the alkali metal salt thereof are arbitrarily selected and used. Its content is 0.0
The content is preferably from 01 to 30% (% indicates% by weight; the same applies hereinafter), more preferably from 0.05 to 10%.

The component (B) of the composition for external use on the skin of the present invention comprises:
Butterfly (mulberry parasitism, mistletoe or mistletoe or mistletoe), Kakyousou (summer hay, mothweed), ibis (return), gossip (cow knee, hinata nokozuchi), sagebrush (mushroom or mugwort or sagebrush or sagebrush), asenyaku (seaweed) Asenyaku, Gambir),
Erica (Gyoryumodoki), Seiko (Pterocarpus or Artemisia), Asiatica, Mokubetsushi, Rhododendron (Marminorushi), Shinanoki (Europea japonicus), Emmeiso (extended life grass, Hiokiokoshi or Kurobanahiokioshi), Ashitaba or Nabenai (continued) At least one selected from the extracts of A. spp., S. aureus and S. aureus, and preferably at least one selected from the extracts of Yakumoso, Odikosou, Soukysei, Kakosou and Touki.

The plant extract which is the component (B) of the present invention comprises:
Whole grass, whole tree, or aboveground, underground, or leaves, stems, stems, branches, buds, flowers, seeds of the plant,
From the pod, fruit, root, bulb, or bark, heartwood, mesophyll, etc., squeeze or extract with a suitable solvent, or after drying, crush and crush as necessary and use an appropriate solvent. It can be obtained by performing extraction. Solvents include water, alcohols such as methanol and ethanol, polyhydric alcohols such as ethylene glycol and propylene glycol, organic solvents such as acetone, hexane, and chloroform, combinations of these solvents, and even carbon dioxide. Supercritical extraction is also possible. What is extracted in this way, as it is or as a diluent,
Alternatively, it may be used as a concentrated extract, as a dry powder by freeze-drying or the like, or as a paste. After the extraction operation, it can be purified by activated carbon or column chromatography.

The ratio of the concentration of the component (A) to the concentration of the component (B) in the external composition for skin of the present invention is 1: 500 by weight.
0.00 to 5000: 1, preferably 1: 4000 to 1
00: 1 is preferable, and especially 1: 200 to 50: 1 is preferable.

In addition to the essential components of the above-mentioned components (A) and (B), the skin external preparation composition of the present invention may contain, if necessary, a normal skin external preparation as long as the effects of the present invention are not impaired. Various components used in the composition, such as oil,
Water, surfactants, moisturizers, alcohol, thickeners,
Antioxidants, sequestering agents, pH adjusters, preservatives,
Flavors, dyes, 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, a solubilizing system, an emulsifying system, a powder dispersing 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.

[0023]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited to these Examples. Example 1 Using the ellagic acid-based compound shown in Table 1 as the component (A) of the present invention and various extracts shown in Table 1 as the component (B), the skin whitening effect was evaluated according to the following method. . [Preparation] 100 g of dried whole plant of Yakumoso
Was added with 10 times (w / v) ethanol, and the mixture was extracted with stirring at room temperature for 2 hours. Next, the mixture was filtered, and ethanol was distilled off under reduced pressure to obtain 19 g of an extract. Other plants were extracted in the same manner, but the solvent having a high boiling point was used without being distilled off. [Comparative Experiment] The whitening effect (melanin production inhibitory effect) of the A component and the B component on B16 melanoma cells was examined. <Cell culture method> Culture of B16 melanoma is 10% FB
Performed using Eagle's medium containing S and 0.5 mM theophylline. The cells were seeded at a density of 0.75 × 10 ⁴ cells / cm ² and cultured at 37 ° C. in a carbon dioxide incubator (5% CO ₂ ). After 24 hours of the culture, the medium containing the component (A) at a final concentration of 4 μM and the component (B) containing the final concentration of 10 ⁻³ wt%, or the medium alone as a control, was replaced, and the cells were further cultured for 72 hours. <Visual measurement of the amount of melanin> 72 hours after the addition of the sample solution,
After removing the sample solution and washing with a phosphate buffer, the cells on the plate were detached with a cell detacher. The exfoliated cells were collected in a centrifuge tube, centrifuged to precipitate, and the degree of whitening was visually determined in comparison with a control without addition of a sample according to the following criteria. Table 1 shows the results.

[0024]

Table 1- (1): Fading effect of cells

[0025]

Table 1- (2): Fading effect of cells

As shown in Table 1, a strong inhibitory effect on melanin production was observed due to the coexistence of the components A and B. Less than,
The example which mix | blends the melanin production inhibitor of this invention is shown.
The following examples all showed an excellent pigmentation-suppressing effect, and also had good safety.

Example 2 An oil phase component and an aqueous phase component shown in Table 2 were separately dissolved by heating at 70 ° C., 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.

[0028]

[Table 2] (Emulsion)

Example 2 The components shown in Table 3 were mixed to prepare a serum.

[0030]

[Table 3] (Serum)

Example 3 A serum was prepared by mixing the components shown in Table 4.

[0032]

[Table 4] (Serum)

Example 4 A cream was prepared by mixing the ingredients shown in Table 5.

[0034]

[Table 5] (Cream)

Example 5 A lotion was prepared by mixing the components shown in Table 6.

[0036]

[Table 6] (Lotion)

Example 6 An emulsion was prepared by mixing the components shown in Table 7.

[0038]

[Table 7] (Emulsion)

Example 7 A cosmetic liquid was prepared by mixing the components shown in Table 8.

[0040]

[Table 8] (Serum)

Example 8 A cream was prepared by mixing the ingredients shown in Table 9.

[0042]

[Table 9] (Cream)

Example 9 A cream was prepared by mixing the ingredients shown in Table 10.

[0044]

[Table 10] (Cream)

[0045]

The composition for external use on the skin of the present invention uses an ellagic acid-based compound represented by the general formula (1) and an alkali metal salt thereof, which are useful as a whitening agent. Odorikosou, Sukikisei (mulberry parasitism, mistletoe or mistletoe, or mistletoe), Kakosou (summer hay, mothweed), ibis (go), gossip (cow knee, hinotainokozuchi), sagebrush (mushroom or mugwort or sagebrush) , Asenyaku (Asenyaku, Gambir), Erica (Goldfish), Seiko (Gourd carrot or Artemisia), Mushroom, Mokubetsushi, Rhododendron (Marminorumushi), Shinanoki (Galleria japonicus), Emmeiso (Enmeisou, Hikiokoshi or Kuroboshi) Ashitaba, pan (Interruption or river interruption, tounabena or cinnabena) extract, preferably at least one selected from the extract of Yakumoso, odorikosou, sukiyase, sycamore, touuki ("component B"). When used in combination, the composition improves the skin whitening effect and is excellent in safety, stability and odor.

Claims (1)

[Claims] (A) The following general formula (1): (In the formula, R ₁ , R ₂ , R ₃ and R ₄ represent a hydrogen atom and a carbon atom of 1 to 1.
An alkyl group of 20; an acyl group having 1 to 20 carbon atoms;
(CmH ₂ m-O) nH (where m is 2 or 3 and n is 1
(The above integer) or a (poly) oxyalkylene group represented by the following structural formula 2 Which may be the same or different, and R ₅ represents a hydrogen atom, a hydroxyl group or an alkoxy group having 1 to 8 carbon atoms. At least one compound selected from the group consisting of ellagic acid compounds and alkali metal salts thereof represented by the formula (B): Yakumoso (mass mother plant, mehajiki), odorisou, suzukisei (mulberry parasitism, mistletoe or mistletoe or mistletoe), kakosou (Summer haygrass, nepenthes), touki (toki), gossip (cow knees, hinata nokozuchi), sagebrush (mushrooms, mugwort or sagebrush or sagebrush), sensyaku (Asenyaku, Gambir), erika (gryolimodoki), seiko ( Red carrot or Artemisia), Astragalus, Mokubetsushi, Rhododendron (Marminorushi), Linden (Europea sylvestris), Emperor (Extended life grass, Hiokikosi or Kurobanahiokioshi), Ashitaba, Navena (intermittent or intermittent, Tounabena or Shinabena) A composition for external use on the skin, comprising at least one selected from the extract of (n).