JP3233776B2 - Skin whitening agent - Google Patents

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 whitening skin, which has an extremely high level of safety to the skin, prevents spots, freckles, darkness, etc., alleviates symptoms and suppresses exacerbation, and furthermore, sunburn. Another object of the present invention is to provide a skin whitening external preparation which can be used effectively as a cosmetic, a medicated cosmetic or an external medicine for the purpose of skin whitening such as skin recovery after snowing.

[0002]

2. Description of the Related Art Blots, freckles, and dark spots are caused by the deposition of skin pigment (melanin). It is considered to be the biggest cause of suffering, and beauty whitening has been an extremely big problem. Therefore, spots,
External preparations for whitening that improve, alleviate or prevent pigmentation symptoms such as freckles have been of great interest to consumers from the viewpoint of both basic cosmetics and treatment. Heretofore, whitening agents such as ascorbic acid, glutathione, and sulfur preparations have been mainly used as such external preparations for whitening.
In particular, ascorbic acid has long been known to be effective for abnormal pigmentation of the skin such as melanosis of Lille. That is, ascorbic acid inhibits tyrosine-tyrosinase action in the melanin production mechanism in the skin, or inhibits melanin production in order to generate doperquinone by reducing the melanin-producing intermediate doperchrome in the opposite direction to its metabolic process. It is said that this suppresses abnormal pigmentation of the skin. Therefore, conventionally, oral administration of ascorbic acid has been performed in the dermatology field for acquired pigmentation such as spots and melanosis. However, ascorbic acid is water-soluble and has problems in skin absorbability and oxidative stability.Therefore, when applied to external preparations such as whitening cosmetics or medical ointments, esterified products with higher fatty acids or phosphoric acid (Liposoluble ascorbic acid). On the other hand, drugs such as glutathione and sulfur preparations have been reported to have an effect of inhibiting melanin production, and have been widely used in external preparations for the purpose of preventing spots, freckles, etc. and alleviating symptoms.

[0003]

However, there is a problem that even when the above-mentioned ascorbic acid derivative or glutathione is used as an external preparation for skin, the whitening effect is not sufficiently satisfactory. In addition, glutathione and sulfur preparations have a peculiar off-flavor and may not precipitate enough when used in water-soluble cosmetics. Were present.

Therefore, in the industry, skin external preparations for skin whitening, which are of great interest to consumers in terms of basic cosmetics, such as spots, freckles, and black and white, have extremely high safety without causing skin disorders and the like. It has been desired to create a skin whitening agent for external use that is extremely effective in alleviating or preventing skin irritation and has excellent stability over time.

[0005]

According to the present invention, silane (Bl
The present invention solves all of the above-mentioned conventional problems by providing a skin whitening external preparation characterized by comprising an extract of E. etilla striata Reichb. fil.) as an active ingredient.

[0006]

The constitution of the skin whitening agent for external use according to the present invention will be described in detail below. In the present invention, silane (Bletil
la striata Reichb. fil.) extract is regarded as the active ingredient.
Here, silane (Bletilla striata Reichb. Fil.)
Orchidaceae distributed in Japan and China west of Kanto (Or
chidaceae) is a kind of perennial herb that has a row of spherical white succulent bulbs in the basement, several leaves in the lower half of the stem at a height of about 50 cm, and leaf blades are oblong It is 15-30cm long and 3-5cm wide, has sharp edges, and has many longitudinal veins. The flower is a large plant of 3 to 8 plants lined up at the top of the stem. This silane (Bletilla striata Reichb. Fil.)
A dried and prepared underground bulb is called "BLETILLAE TUBER" under the name of a crude drug, and has been used as one of the crude drug formulations having medicinal properties such as hemostasis, drainage, mucous slip and the like since ancient times.

The silane used in the present invention (Blet
illa striata Reichb.fil.), the site is not particularly limited, leaves, stems, above-ground parts such as flowers, fruits, underground bulbs, or whole plants can be used as appropriate, More desirably, an underground bulb is preferably used. Such a silane (Bletilla striata Reichb. Fil.) Is dried if necessary, crushed and extracted with an appropriate solvent. As the extraction solvent, any solvent can be used without particular limitation as long as it is a solvent generally used for plant extraction, such as a polar solvent, a non-polar solvent or a mixed solvent thereof.

Specific examples of the polar solvent include water, alcohols such as methanol, ethanol, isopropanol, n-propanol, isobutanol, n-hexanol, methylamyl alcohol, 2-ethylbutanol and n-octanol, ethylene glycol, and the like. Polyhydric alcohols such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol, propylene glycol monomethyl ether, propylene glycol monoethyl ether, triethylene glycol, 1,3-butylene glycol, hexylene glycol and derivatives thereof, and acetone , Methyl acetone,
One or more mixed solvents of ketones such as methyl ethyl ketone, methyl isobutyl ketone and methyl-n-propyl ketone, esters such as ethyl acetate and isopropyl acetate, and ethers such as ethyl ether, isopropyl ether and n-butyl ether Is exemplified as a preferred embodiment, but is not particularly limited.

As the non-polar solvent, petroleum ether, n-
Hexane, n-pentane, n-butane, n-octane,
Preferred examples include aliphatic hydrocarbons such as cyclohexane, and one or more mixed solvents such as carbon tetrachloride, chloroform, dichloromethane, trichloroethylene, benzene, and toluene, but are not particularly limited thereto.
Further, the above-mentioned mixed solvent of a polar solvent and a non-polar solvent can be used without limitation in the present invention.

In the present invention, silane (Bletilla str
The iata Reichb. fil.) extract may be used as it is in the form of a filtrate, or may be used in the form of a powder after evaporating the solution to dryness. Further, the liquid or powder can be used as it is as an external preparation for skin, but more preferably mixed with a known excipient or diluent, or any other compounding material, granules, emulsions, It is used after being prepared into a dosage form such as a solution or a suspension. In the present invention, the final form of the skin external preparation may be a cosmetic applied to healthy skin for the purpose of beauty, or a medicinal product having a specific purpose of use such as alleviation of spots, freckles, and recovery of skin after sunburn. They may be cosmetics (quasi-drugs) or pharmaceuticals for treating spots and the like, and any form may be arbitrarily adopted. In preparing these dosage forms, ascorbic acid or a derivative thereof known as a whitening agent, a sulfur preparation, glutathione, or the like, or a moisturizing agent, an ultraviolet absorber, vitamins, and other commonly used known additives are used in the present invention. Can be used in combination as long as the effect of (1) is not impaired.

Further, in such a skin whitening agent for external use, the silane (Blet) may be added at any stage of the production process.
illa striata Reichb. fil.) extract may be mixed in any amount. The compounding amount was 0.00% as dry weight.
It may be added in an amount of 1% by weight or more, more preferably 0.01% by weight or more, and may be appropriately set as appropriate depending on the purpose of use and dosage form.

[0012] (Formulation Example) Hereinafter, the configuration of whitening skin <br/> Hadagaiyo agent according to the present invention by way of Formulation Examples will be described in detail. (Formulation Example 1) Lotion formulation type wt% silane (Bletilla striata Reichb. Fil.) Underground bulb ethanol extract 10.0 Glycerin 6.0 1,3-butylene glycol 4.0 Polyoxyethylene polyoxypropylene decyltetradecyl Ether 1.0 Preservative qs perfume qs Purified water balance 100.0

(Formulation Example 2) Cream type weight% silane (Bletilla striata Reichb. Fil.) Ethanol extract of underground bulb (dry matter) 0.1 Stearyl alcohol 5.0 Stearic acid 2.0 Hydrogenated lanolin 3. 0 Squalane 10.0 Octyldodecanol 10.0 Propylene glycol 5.0 Polyoxyethylene cetyl ether 2.4 Glycerin monostearate 1.6 Preservatives qs Perfume qs Purified water balance 100.0

(Formulation Example 3) Emulsion formulation weight% silane (Bletilla striata Reichb. Fil.) Ethanol extract of whole plant (dry) 0.2 Squalane 5.0 Vaseline 2.0 Beeswax 0.5 Sorbitan sesquiolein Acid ester 0.5 Polyoxyethylene oleyl ether 0.8 Glycerin 5.0 Carboxyvinyl polymer 0.2 Potassium hydroxide 0.1 Preservative qs Perfume qs Purified water balance 100.0

[0015]

EXAMPLES The effects of the skin whitening agent for external use according to the present invention will be further clarified by giving examples.
However, the present invention is not limited at all by the following examples. (Example 1) 50 ml of ethanol was added to 100 g of dried and ground material of the underground bulb portion of silane (Bletilla striata Reichb. Fil.), Immersed and extracted at room temperature all day and night, and the extract was filtered and concentrated to extract ethanol. 0.82 g of the product was obtained, and this extract was used as the whitening agent of Example 1. Comparative Example 1 Magnesium ascorbic acid phosphate was used as the whitening agent of Comparative Example 1. Comparative Example 2 Reduced glutathione was used as the whitening agent of Comparative Example 2.

[0016]

[Test Example] (Test Example 1) Measurement of Tyrosinase Biosynthesis Inhibition Effect B16 melanoma 4F5 (RIKEN Cell Bank) cultured in 10% FBS-DMEM was seeded on a 96-well plate at 5 × 10 ⁴ cells / well ( total volume 195μl), 2 at 37 ° C., of 5% -CO ₂ conditions
The cells were cultured for 4 hours. Here, the final concentrations of the whitening agents obtained in the above Examples and Comparative Examples are 5, 10, 50, 100, and 500 pp, respectively.
The solution was prepared with a 50% ethanol / PBS solution so as to have a volume of m, filtered and sterilized with a 0.2 μm membrane filter, and added in 5 μl portions, and cultured for further 24 hours under the same conditions. After completion, remove the culture and remove 1% Triton X-100 / PB
After solubilizing the cell membrane with 50 μl of S solution, 10 mM
100 μl of L-DOPA was added and reacted at 37 ° C. for 4 hours. The reaction was stopped by adding 50 μl of methanol to the reaction system,
The absorbance at a wavelength of 475 nm was measured using a microplate reader. As a control, the absorbance of the reaction system without adding the whitening agent of the example and the comparative example was measured, and the tyrosinase biosynthesis inhibition rate (%) was calculated from the absorbance based on the following formula (1). did. Table 1 shows the results.

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[0017]

[Table 1]

(Test Example 2) Measurement of cell viability B16 melanoma 4F5 (RIKEN Cell Bank) cultured in 10% FBS-DMEM was seeded on a 96-well plate at 5 × 10 ⁴ cells / well (total volume: 195 μl). At 37 ° C, 5% -CO ₂
Cultured for 24 hours. Here, the final concentrations of the whitening agents obtained in the above Examples and Comparative Examples were 5, 10, 50, 100, and 500 pp, respectively.
The solution was prepared with a 50% ethanol / PBS solution so as to obtain a filter solution of m, filtered and sterilized with a 0.2 μm membrane filter, and added in 5 μl portions, followed by further culturing under the same conditions for 24 hours. The viability of this cultured cell was measured by the MTT test method. First, remove the culture solution and add 10% of 5% to each well.
D-MEM medium containing mg / ml MTT solution was added. 37 ℃
For 4 hours. After the reaction, 100 μl of 0.04 N hydrochloric acid-isopropanol solution was added, and the color was developed for 30 minutes.
The absorbance at 0 nm and 655 nm was measured. As a control, the absorbance of the example and the comparative example in the case where the whitening agent was not added was measured, and the cell viability (%) was calculated from the absorbance based on the following formula 2 (Chemical Formula 2). Table 2 shows the results.
Shown in

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[0019]

[Table 2]

As is clear from the results of Test Example 1, the whitening agent of the present example has a low concentration of 500 ppm.
It showed about 50% tyrosinase biosynthesis inhibitory action. Moreover, the whitening agents of the examples exhibited an extremely high tyrosinase biosynthesis inhibition rate, and exhibited a sufficient whitening effect, as compared with ascorbic acid esters and glutathione which have been conventionally used as whitening agents. . further,
500ppm with sufficient tyrosinase biosynthesis inhibitory action
At the level of the concentration, no toxicity to the cells was observed, indicating that the whitening agents of Examples are highly safe.

[0021]

As described in detail above, the present invention is a skin whitening preparation for external use characterized by comprising a silane (Bletilla striata Reichb. Fil.) Extract as an active ingredient. As is clear, the safety on the skin is extremely high, and it shows an effective tyrosinase biosynthesis inhibitory action, preventing spots, freckles, darkness, etc. or alleviating symptoms and suppressing exacerbation, and even after sunburn, after snowing It has an excellent effect that it can be used effectively and versatile as a cosmetic, medicated cosmetic, or external medicine for the purpose of skin whitening such as skin recovery.

──────────────────────────────────────────────────続 き Continuation of front page (72) Inventor Nobunori Fujiwara 5-12, 12-ken, Chuo-ku, Osaka-shi Inside Mandom Central Research Laboratory Co., Ltd. (56) References JP-A-57-102809 (JP, A) JP-A-5-155738 (JP, A) JP-A-5-310549 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K ^7/ 00-7/50 A61K 35/78

Claims (1)

(57) [Claims] 1. Silane (Bletilla striata Reichb. Fi)
l.) Whitening characterized by comprising an extract as an active ingredient
External preparation for skin.