JP3072024B2 - Whitening agent and skin external preparation - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a whitening agent and an external preparation for the skin.
The present invention also relates to a whitening agent and a skin external preparation capable of preventing and treating spots and freckles due to sunburn and the like.

[0002]

2. Description of the Related Art Blots, freckles, and pigmentation on skin after sunburn occur with aging and are difficult to increase or disappear with aging, which is a problem for middle-aged and elderly people. Although the mechanism of the onset of these pigmentation diseases has not been clarified yet, it is considered that the mechanism of melanin synthesis in epidermal melanocytes has been enhanced by the action of sunlight, particularly ultraviolet rays, and melanocyte stimulating hormone.

[0003] In addition, it is considered that the keratinization of epidermal keratinocytes (keratinocytes) with aging also causes an increase in the density of melanin granules in the epidermis, that is, a symptom of clinically increasing pigmentation. These pigmented areas are localized and may have a clear difference from the surrounding normal skin color.

[0004] There is a strong demand for the development of a drug capable of restoring such acquired pigment (ie, melanin) deposits to a normal skin color, and many drugs have been commercialized so far. For example, in recent years, cosmetics containing a vitamin C (L-ascorbic acid) derivative having excellent reducing ability have been proposed. However, this also has difficulty in stability, and almost no effect is observed in external use.

[0005] On the other hand, it is known in the United States and Europe that hydroquinone has a therapeutic effect on stains and an effect on whitening black skin.
Allergenicity), and there are cases in which vitiligo is produced. In addition, various components such as isoflavone derivatives (JP-A-58-225004) and p-hydroxycinnamic acid derivatives as cinnamic acid derivatives (JP-A-59-196813) are known as melanin inhibitors. Have been.

[0006]

However, at present, there is no known substance which has a sufficient effect of preventing and improving pigmentation and its incorporation into a cosmetic base material. Accordingly, an object of the present invention is to provide a whitening agent and a skin external preparation which have an excellent whitening effect and contain a component useful as a cosmetic component.

[0007]

Under such circumstances, the present inventor has studied the mechanism of melanin production to suppress the production of melanin in melanocytes and reduce or eliminate pigmentation caused by external stimuli such as ultraviolet rays. As a result of diligent studies to obtain a substance to be made, it was found that malvaric acid has an excellent pigmentation prevention / improvement effect, and that a skin external preparation containing this has a good effect on pigmentation reduction / elimination. As a result, the present invention has been completed. In addition, the fact that malvaric acid suppresses the production of melanin has not been known at all, and is a finding obtained by the present inventors.

[0008] That is, the present invention provides a whitening agent and a skin external preparation containing malvalic acid.

[0009] Malvaric acid used in the present invention is represented by the following formula (1).

[0010]

Embedded image

Malvaric acid (1) is, for example, Usvenita
Chestnut (Althaea officinali)
s), hollyhock (Althaea rosea), etc.
Has been reported to be obtained from some mallows
(J. Am. Oil Chem. Soc.,4
2, P885-887 (1965)).

Malvulinic acid (1) is obtained by pulverizing one or more of the leaves, flowers, seeds, roots and stems of the whole plant of the Malvaceae plant, or without pulverizing them, and then cooling them to normal temperature or heating. The components obtained by extraction with a solvent or extraction with an extraction device such as a Soxhlet extractor at a temperature can be easily isolated by subjecting the components to chromatography as usual.

The amount of malvalic acid (1) in the whitening agent and the external preparation for skin of the present invention is not particularly limited, but is usually 0.00 from the viewpoints of efficacy, compoundability, feel and the like.
It is preferable that the content be 0.01 to 5% by weight,
It is particularly preferred to be 2.5% by weight.

Further, the whitening agent and skin external preparation of the present invention include:
In addition to the malvaric acid within a range that does not impair the effects of the present invention, ordinary cosmetics, various optional ingredients blended in quasi-drugs and topical drugs, such as oils, humectants, thickeners, preservatives, emulsifiers, Pigments, powders, pH adjusters, medicinal ingredients, ultraviolet absorbers, antioxidants, fragrances and the like can be appropriately compounded.

Examples of oils include natural oils such as soybean oil, bran oil, jojoba oil, avocado oil, almond oil, olive oil, cacao oil, sesame oil, persic oil, castor oil, coconut oil, mink oil, tallow, lard, etc. And hardened oils obtained by hydrogenating these natural fats and oils, and synthetic triglycerides such as glyceride myristic acid and triglyceride 2-ethylhexanoate. Examples of the wax include carnauba wax, whale wax, beeswax, and lanolin. Examples of the hydrocarbons include liquid paraffin, vaseline, paraffin microcrystalline wax, ceresin, squalane, and bristan. Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, lanolinic acid, isostearic acid and the like. Examples of higher alcohols include lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, 2-hexyldecanol, and the like. Esters include cetyl octanoate, triglyceride octanoate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, octyl dodecyl myristate,
Isopropyl palmitate, isopropyl adipate,
Examples include butyl stearate, decyl oleate, cholesterol isostearate, POE sorbitol fatty acid ester and the like. Essential oils include peppermint oil, chamomile oil, jasmine oil, show brain oil, hinoki oil, spruce oil,
Ryu oil, turpentine oil, cinnamon oil, bergamot oil, mandarin oil, shobu oil, pine oil, lavender oil, bay oil, clove oil, hiba oil, rose oil, eucalyptus oil, lemon oil, thyme oil, peppermint oil, rose Oil, sage oil,
Menthol, cineole, eugenol, citral,
Citronellal, borneol, linalool, geraniol, camphor, thymol, spiranthol, pinene, limonene, terpene-based compounds and the like can be mentioned. Examples of the silicone oils include dimethylpolysiloxane. These oily components can be used alone or in combination of two or more. In the present invention,
Among them, myristic acid glyceride, 2-ethylhexanoic acid triglyceride, lanolin, liquid paraffin, petrolatum, paraffin microcrystalline wax, squalane, lauric acid, myristic acid, palmitic acid,
Linoleic acid, linolenic acid, isostearic acid, cetyl alcohol, stearyl alcohol, oleyl alcohol, cholesterol, cetyl octanoate, triglyceride octanoate, isopropyl myristate, octyl dodecyl myristate, cholesterol isostearate, POE sorbitol fatty acid ester, peppermint oil, It is preferable to use spruce oil, cinnamon oil, rose oil, menthol, cineol, eugenol, citral, citronellal, geraniol, pinene, limonene, dimethylpolysiloxane. The content of the oil in the whitening agent and the external preparation for skin can be appropriately selected according to the dosage form of the whitening agent and the external preparation for skin, and can be usually 0.1 to 95% of the total amount of these. .

As humectants, sorbitol, xylitol, glycerin, maltitol, propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, sodium pyrrolidonecarboxylate, lactic acid, sodium lactate, polyoxypropylene fatty acid ester,
Polyethylene glycol and the like. Examples of the thickener include water-soluble polymers such as carboxyvinyl polymer, carboxymethylcellulose, polyvinyl alcohol, carrageenan, and gelatin; and electrolytes such as sodium chloride and potassium chloride. Preservatives include urea, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, sodium benzoate and the like. Examples of the emulsifier include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hardened castor oil, polyoxyethylene sorbitol fatty acid Examples include nonionic surfactants such as esters. Powders include talc, sericite, mica, kaolin, silica, bentonite, vermiculite, zinc white, mica, mica titanium,
Examples include titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, red iron oxide, iron oxide, and ultramarine.
Examples of the pH adjuster include buffers such as lactic acid-sodium lactate and citric acid-sodium citrate.

The whitening agent and the external preparation for skin of the present invention can be produced by a conventional method. Further, the whitening agent and skin external preparation of the present invention are not limited to general skin cosmetics, but include quasi-drugs, external medicines, and the like,
The dosage form can be arbitrarily selected depending on the purpose, such as cream, emulsion, lotion, foundation, pack, lotion, gel, solution, stick and the like.

[0018]

EFFECTS OF THE INVENTION A skin external preparation containing malvalic acid has an excellent whitening effect, a preventive and therapeutic effect on spots and freckles caused by sunburn and the like, and is highly safe.

[0019]

Next, the present invention will be described specifically with reference to examples, but the present invention is not limited to these examples.

Example 1 (Effect of cultured human melanocytes on melanin production): Samples of various concentrations were added to a culture plate of normal human melanocytes, and the effect on melanin production of cells was examined.

(Test Method) Normal human melanocytes (trade name: Melanopack) commercially available from Kurabo Co., Ltd. were subcultured according to a conventional method, and used for this test. After adding a sample to this cell culture plate so that the final concentration was 0.00001 to 100 μM, the effect of melanocytes on melanin production after a certain period was examined. The effect on melanin production was determined by quantifying the amount of radioactive thiouracil incorporated into the cells, collecting the cells, visually determining the color tone of the cell pellet, and assigning an evaluation score of 1 to 4. The color tone was determined according to the following criteria. The evaluation was shown by the average of the evaluation points of 10 culture plates.

[0022]

[Table 1]

(Results) As shown in FIG. 1, the uptake of radioactive thiouracil into cells was significantly suppressed by the addition of a sample of 0.001 μM or more as compared with the untreated sample.

Further, as shown in Table 2, in the visual judgment of the color tone of the cell pellet, clear whitening of the cells was observed with malvaric acid at a concentration of 10 μM. From the above results, an inhibitory effect of malvaric acid on melanin production of cultured human melanin-producing cells was confirmed.

[0025]

[Table 2]

Example 2 (Annihilation effect on UVB pigment spots): After carefully shaving the back hair of 20 brown guinea pigs with a hair clipper and a shaver, the ultraviolet rays in the UV-B region were reduced to the minimum erythema dose (MED) of 2. Double doses were irradiated once a day for 3 days to induce pigment spots. 2 days a day
The amount of pigment spot disappearance was determined by continuously applying an evaluation sample (80% ethanol solution containing 1.0% malvanic acid, μl) to the test site for one month. Also,
As a control, a sample to which only ethanol was applied was tested in the same manner as the sample.

The evaluation was performed using a color difference meter (CMS-1 manufactured by Murakami Color Co., Ltd.).
200), and from the obtained Munsell value, L
^* Calculate the value, and from the ΔL ^* (time-dependent change) of the sample application site, the ΔL ' ^{* of the} sample non-application site (solvent only = control)
(ΔΔL ^* ) after subtracting (temporal change). Note that ΔΔL ^* is represented by the following equation.

[0028]

[Table 3]

[0029] L ^* _0; sample application measurement site before coating L ^'* _0; site of sample uncoated test before applying L ^* _1; the sample before applying the coating measurement site L' ^* _1; before coating sample Unapplied test site

The evaluation is shown by the average value of the evaluation points of 20 test animals (Table 4).

[0031]

[Table 4]

The whitening agents and skin external preparations shown in Examples 3 to 8 were prepared according to a conventional method.

Example 3 (cream)

Table 5 Composition (%) (1) Glycerin monostearate 5.0 (2) Polyethylene glycol mostaterate 2.0 (3) Squalane 8.0 (4) Stearyl alcohol 5.0 (5) Glyceryl trioctanoate 8.0 (6) Dimethylpolysiloxane (50cs) 0.5 (7) Glycerin 5.0 (8) Citric acid 0.5 (9) Sodium citrate 0.5 (10) Malvalic acid 1.0 (11) 6-amino-n-caproic acid 0.5 (12) Purified water Remaining amount (13) Preservative appropriate amount (14) Flavor appropriate amount

Example 4 (Essence)

Table 6 Composition (%) (1) 1,3-butylene glycol 8.0 (2) glycerin 4.0 (3) Xanthan gum 0.3 (4) Colloidal sodium sulfate 0.1 (5) Sodium hyaluronate 0 .1 (6) Ethanol 3.0 (7) Polyoxyethylene sorbitan monostearate (6E.O.) 0.5 (8) Malvaric acid 1.0 (9) Glycine 0.5 (10) Purified water (11) Preservative appropriate amount (12) Flavor appropriate amount

Example 5 (Emulsion)

Table 7 Composition (%) (1) Polyoxyethylene sorbitan tristearate 1.0 (20E.O.) (2) Glyceryl oleate 1.0 (3) Glyceryl monostearate 0.5 (4) Squalane 6.0 (5) Glyceryl trioctanoate 2.0 (6) Cetyl octoate 2.0 (7) Stearyl alcohol 2.0 (8) Octyl methoxycinnamate 2.0 (9) 1,3-butylene glycol 0 (10) Glycerin 3.0 (11) Malvaric acid 0.001 (12) Nicotinamide 1.0 (13) Purified water Remaining (14) Preservatives appropriate amount (15) Fragrance appropriate amount

Example 6 (Lotion)

Table 8 Composition (%) (1) 1,3-butylene glycol 6.0 (2) glycerin 4.0 (3) Sodium hyaluronate 0.1 (4) Ethanol 5.0 (5) Polyoxyethylene Oleyl ether (20E.O.) 0.3 (6) Disodium edetate 0.1 (7) Sodium citrate 1.0 (8) Malvaric acid 0.05 (9) Ammonium chloride 0.5 (10) L -Magnesium ascorbyl phosphate 3.0 (11) Purified water Remaining (12) Preservative appropriate amount (13) Flavor appropriate amount

Example 7 (creamy foundation)

Table 9 Composition (%) (1) Dimethylpolysiloxane (6cs) 10.0 (2) Methylphenylpolysiloxane 3.0 (3) Octamethylcyclotetrasiloxane 10.0 (4) Polyoxyalkylene-modified silicone 5 0.0 (5) Titanium oxide 5.0 (6) Sericite 2.0 (7) Talc 3.0 (8) Bengala 0.4 (9) Iron oxide yellow 0.7 (10) Iron oxide black 0.1 (11) Glycerin 5.0 (12) Malvaric acid 0.005 (13) 6-Amino-n-caproic acid 0.5 (14) Purified water Remaining (15) Preservative proper amount (16) Flavor proper amount

Example 8 (pack)

Table 10 Composition (%) (1) Dipropylene glycol 3.0 (2) Polyethylene glycol 3.0 (3) 1,3-butylene glycol 1.0 (4) Glycerin 2.0 (5) Pyrrolidone carboxylic acid Sodium 1.0 (6) Malvaric acid 0.001 (7) Lactic acid 0.5 (8) Sodium lactate 0.5 (9) Polyvinyl alcohol 12.0 (10) Ethanol 3.0 (11) Polyoxy monostearate Ethylene sorbitan (6E.O.) 0.3 (12) Remaining purified water (13) Suitable amount of preservative (14) Suitable amount of fragrance

[Brief description of the drawings]

FIG. 1 is a view showing the effect of malvaric acid on the uptake of radioactive thiouracil into cells.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI // A61K 35/78 A61K 35/78 C (72) Inventor Yukihiro Yada 2-1-3 Bunka, Sumida-ku, Tokyo Kao Corporation Within the research laboratory (72) Inventor Genji Imokawa 2606 Akabane, Kaiga-cho, Haga-gun, Tochigi Prefecture Within the research laboratory of Kao Corporation (56) References JP-A-64-66105 (JP, A) (58) Fields investigated (Int. ⁷ , DB name) A61K ^7/ 00-7/50 CA (STN) REGISTRY (STN)

Claims (4)

(57) [Claims] 1. A whitening agent containing malvaric acid. 2. The malvaric acid content is from 0.0001 to 0.001.
The whitening agent according to claim 1, which is 5% by weight. 3. An external preparation for skin containing malvaric acid. 4. The malvaric acid content is from 0.0001 to 0.0001.
The external preparation for skin according to claim 3, which is 5% by weight.