JPH0761915A - External agent for skin - Google Patents

Abstract

PURPOSE:To obtain an external agent for skin having an improved durability of whitening activity by' synergistically enhancing the whitening activity of kojic acid and/or its derivative and increasing the skin-fitting activity. CONSTITUTION:An external agent for skin is obtained by compounding kojic acid and/or its derivative with one or more kinds of extracts of plants selected from the group consisting of acerola, ginkgo, Ceratonia siliqua, fruit of Rosa multiflora, cranesbill, beefsteak plant, cinnamon, Origanum majorana, thyme, paprika, hip, orchid, lupin.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel skin external preparation having an excellent skin-whitening effect and a feeling of use, and more specifically, it synergistically enhances the skin-whitening effect of kojic acid and / or its derivatives, The present invention relates to an external preparation for skin in which the familiarity is increased to improve the sustainability of the skin-whitening effect.

[0002]

2. Description of the Related Art It is known that spots such as spots and freckles appearing on human skin are mainly caused by deposition of Eumelanin. Various kinds of cosmetics have been studied for a long time in order to suppress the production of melanin, which causes such spots and freckles, and to lighten the skin as a whole. Examples of such attempts include blending hydrogen peroxide and peroxides such as zinc perborate into cosmetics, and blending vitamin C, cysteine, colloidal sulfur, and the like into cosmetics. However, none of them has been satisfactory in terms of preservability and whitening effect.

The present inventors have been conducting research for many years on an external preparation for removing spots such as spots and freckles appearing on human skin to enhance the skin-whitening effect of the whole skin, and the results show that normal humans have Factors related to skin color include melanin, carotene amount, blood flow (oxidized and reduced hemoglobin), skin thickness and transparency, and light is reflected, absorbed and scattered by these factors to change skin color. However, among these, it was clarified that melanin, especially brown or black eumelanin, was the main factor of pigmentation among them, and we searched for a substance that suppresses the production of melanin.

In the study, it was found that kojic acid (5-oxy-2-oxymethyl-γ-pyrone) and its derivatives have an extremely excellent melanin production inhibitory action, and a fair-white makeup containing them as an active ingredient. Have invented a chemical and an external preparation and have provided them to the market (Japanese Patent Publication No. 56).
-18569, JP-A-54-92632,
JP-A-56-79616, JP-A-56-7727
No. 2, JP-A-56-7776, JP-A-56-
7710, JP-A-56-20330, JP-B-63-24968).

These fair-whitening cosmetics and external preparations are used in commercial forms such as creams, lotions, emulsions, packs, lotions, ointments and poultices, all of which suppress excellent melanin production, It is used as a cosmetic or external preparation that produces a whitening effect. However, these cosmetics or external preparations containing kojic acid or a kojic acid derivative do not cause any problem in normal use, but in terms of the persistence of the whitening effect after application to the skin. It is not always sufficient, and in some cases, it is not suitable for ensuring the compliance of patients with severe pigmentation requiring long-term continuous use.

[0006]

DISCLOSURE OF THE INVENTION As a result of intensive studies to improve the above-mentioned drawbacks of the prior art, the present inventor found that a specific plant extract was contained in an external preparation for skin containing kojic acid and / or its derivative. When used in combination, an excellent whitening effect is obtained due to the synergistic effect of both, and the familiarity of kojic acid and / or its derivative with the skin is further enhanced.
The present invention has been completed by finding that the whitening effect is sustained.

[0007]

Means for Solving the Problems That is, the present invention relates to kojic acid and / or an acid derivative thereof, and acerola, ginkgo, locust bean, ages, ginger ginger, perilla, cinnamon, sweet mayonnaise, thyme, paprika, hip, orchid. A skin external preparation having a good feeling of use, which contains one or more plant extracts selected from the group consisting of lupine and excellent in whitening action and its sustainability.

[0008]

Detailed Description of the Invention Kojic acid (5-oxy-2-oxymethyl-γ-pyrone) used in the present invention is a pure product of 5-oxy-2-oxymethyl-γ-pyrone, kojic acid. A fermentation broth containing kojic acid as a main component obtained by culturing a known strain having productivity, a concentrated solution of the fermentation broth, and a crystallized extract of kojic acid from the fermentation broth are used. .

Examples of the kojic acid derivative are, for example, Japanese Patent Publication No. 60-10005, Japanese Patent Publication No. 1-45472, Japanese Patent Publication No. 3-74229, and Japanese Patent Publication No. 58-221.
No. 51, Japanese Patent Publication No. 58-22152, an esterification product of kojic acid and -CH at the 2-position of kojic acid.
Known compounds such as a kojic acid derivative in which a kojic acid molecule is stabilized by binding a saccharide to the ₂ OH group can be used alone or in combination of two or more kinds.

Specific examples of plant extracts used in combination with kojic acid and / or acid derivatives thereof include the following.

Acerola is a fruit of Central and South America containing vitamin C. It is a plant of the Quintraonidae family that grows from the Caribbean Islands to Brazil and bears red fruits similar to cherries and can be harvested 5 to 6 times a year. Also known as West Indian Cherry, the ripe fruit is juicy and has a soft, refreshing and sour aroma. As the extract, a fruit extract can be preferably used.

[0012] Ginko Extract includes ethanol from Ginko biloba leaves,
Those extracted with 1,3-butylene glycol, purified water and the like can be preferably used.

Carob (Ceratonia siliqua) is a tree that grows widely in the Mediterranean region and has a thick trunk with a height of 6 to 10 m. The egg-shaped and supple leaves are evergreen and are assembled in units of 5 to 11. Flowers have no corolla. The fruits are 10 to 20 cm pods and contain oval brown hard seeds. As the extract (Carob Extract),
A fruit extract can be preferably used.

Examples of the Age Fruit Extract (Rose Fruit Extract) include ethanol, 1,3 from pseudo fruit or fruit of Neurose (Rosa multiflora Thunberg) or its related plants.
-The extract obtained by extraction with butylene glycol, purified water or a mixture thereof can be preferably used.

Geranium Herb Ex
As a tract, a geranium ginger (Geranium thunb
An extract obtained by extracting ergii Siebold et Zuccarini (Geraniaceae: Furanoaceae) with 1,3-butylene glycol or an ethanol solution can be preferably used.

[0016] As perilla extract, Perilla frutescens f. Crispa (Leb
iatae: Lamiaceae)) or its close-green plant leaves 1,3-
An extract obtained by extraction with butylene glycol or ethanol solution can be preferably used.

As the cinnamon extract, an essential oil (cinnamon oil) obtained by steam distillation of cinnamon can be preferably used.

Sweet mayonnaise (Origanum majorana)
Are colonies with a height of 20 to 50 cm, their petioles are covered with hair and are angular, and their leaves are small and oval.
It is covered with fluff. The flowers are very small and white or pink with a scent.
As the extract (Sweet Marjoram Extract), the one extracted from the leaves of sweet mayonnaise growing in the Mediterranean region can be preferably used.

Thymus (Thymus serpyllu L.) is a plant of the Labiatae family and is distributed in Eurasia north of the Alps. Since ancient times, it has been used as a remedy and as an essential fragrance for cooking. Wild Thyme Extrac
As t), those obtained by extracting whole grass with ethanol, 1,3-butylene glycol, propylene glycol, purified water and the like can be preferably used.

As a paprika extract, a carotenoid pigment obtained by extracting hexane from a fruit of paprika (Capsicum annum L. (Solanaceae, Solanaceae)) and then distilling hexane off is dissolved in soybean oil. What was said can be used conveniently.

Wild roses grow near the outer edges of forests in Europe, West / North Asia, North Africa and North America, and have thorns and stems, pink petals, and unpaired pinnate leaves. . As the hip extract, those extracted from the fruits of wild roses can be preferably used.

The orchid (Orchidea varilla planifol) is
Mainly grows in Mexico and other tropical or subtropical countries. As the extract (Orchid Extract), leaves extracted with water or ethanol can be preferably used.

Lupine (Lupinus albus) is a plant cultivated as an edible or ornamental plant, and its leaves are finger-shaped.
It has 11 to 11 fan-shaped leaflets. The flowers are dense, spike-shaped and come in a variety of colors. It is actually a flat pod containing hard seeds, slightly larger than a pea. The extract (Lupi
What is extracted from seeds can be preferably used as n Extract).

In the present invention, the amounts of the kojic acid and / or its derivative and the plant extract exemplified above are:
In all cases of cosmetics such as creams, lotions, emulsions, packs, lotions, and essences, and when used as external preparations such as ointments, poultices, plasters, etc. Is 0.000
1 to 20% by weight, preferably 0.01 to 10% by weight, and kojic acid and / or a derivative thereof in an amount of 0.001 to 10% by weight, preferably 0.1 to 5% by weight.

The external preparation for skin of the present invention is not particularly limited as long as it is suitable for external application, and as mentioned above, for example, poultice, plaster, paste, cream, ointment, aerosol, emulsion, It is widely used in the form known as lotions, milky lotions, essences, packs, gels, powders, foundations, sun care, pass salts and the like, quasi-drugs and cosmetics.

In the preparation of the external preparation of the present invention, various known active ingredients which are usually used, for example, carpronium chloride, cepharanthin, vitamin E, vitamin E nicotinate, nicotinic acid, nicotinic acid amide, benzyl nicotinate, and ginger. Peripheral vasodilators such as tincture and capsicum tincture, cooling agents such as camphor and menthol,
Antibacterial agents such as hinokitiol, benzalkonium chloride, undecylenic acid, anti-inflammatory agents such as lysozyme chloride, glycyrrhizin and allantoin, whitening agents such as ascorbic acid and arbutin, placenta extract, liver extract, lactic acid bacterium culture extract, etc. Various extracts derived from plants / microorganisms can be appropriately added and used.

In addition to known active ingredients, base agents such as surfactants and oils and fats, known moisturizers, preservatives, and antioxidants for the above-mentioned pharmaceuticals, quasi-drugs, and cosmetics. Agent, UV absorber / scattering agent, chelating agent, pH adjusting agent,
Various additives such as fragrances and colorants can be used in combination.

[0028]

EXAMPLES Next, examples and experimental examples showing their effects will be shown, but these do not limit the present invention at all.

Experimental Example 1 Mouse melanoma B16 fine
Cell whitening test method A sample is prepared and dissolved in MEM (Eagle's Minimum Essential Medium) so that the final concentration becomes the concentration shown in Table 1.
It was filtered with a sterilization filter having a pore size of 0.45 μm. MEM
The insoluble sample was dissolved in 100 μl of ethanol,
It was added to MEM (in this test, the original plant 1
100 ml of a solvent was added to 0 g, and the mixture was stirred at room temperature for 3 hours, and then the dried plant extract was used for evaporation).

Two plastic petri dishes (made by Falcon,
Each sample was dissolved in 9 cm inner diameter) and filtered to remove bacteria.
8 ml EM, 1 ml FBS (fetal bovine serum) and M
1 × 10 ⁵ cells / ml of B16 cells suspended in 1 ml of EM were added, and the medium was exchanged 3 days after the start of culture, and the cells were cultured at 37 ° C. under 5% CO ₂ and 95% air conditions for a total of 5 days. After culturing, collect the grown cells on the bottom of the dish and
Suspend in osphate buffered saline (PBS),
Centrifugation was performed at rpm for 3 minutes, and the degree of blackening of the obtained cell pellet was visually evaluated, and the results are shown in Table 1.

In Table 1, + -in the visual color tone.
Indicates the following evaluation. -: Shows the same degree of blackening as the non-addition group. +: Shows a slightly lower degree of blackening than the non-addition group. ++: The degree of blackening is clearly smaller than that in the non-addition group. +++: Shows a slightly recognized blackening degree. ++++: White or gray, not black. ++++++: White.

[0032]

[0033]

[0034]

[0035]

Experimental Example 2 Guinea Pig UV Pigmentation
The effect of improving pigmentation was examined using a yellow-brown guinea pig.

[Test Method] Using the back skin of 10 yellow-brown guinea pigs, the back hair of the guinea pig was shaved with a hair clipper and further shaved with an electric razor. The back of this guinea pig is covered with aluminum foil with 5 square holes (2.0 x 2.0 cm) and UV-B (3 SE lamps, 1
Irradiation was carried out at 40 mJ / cm ² ) once a day for 90 seconds and every three days four times. From the irradiation start date, the active ingredient shown in Table 2 (the same plant extract as that used in Example 1 was used) was mixed in the following base and applied continuously for 20 days. After application starts 2
The judgment was made on day 0. The degree of blackening of the skin color was visually judged by the judgment criteria as shown below.

Cream base for test (% by weight) (A) Polyoxy monostearate Ethylene glycol (40E.0.) 2.00 Self-emulsifying glyceryl monostearate 5.00 Stearic acid 5.00 Behenyl alcohol 1.00 Flow Paraffin 1.00 Glycerin trioctanoate 10.00 Preservative Suitable amount Perfume Small amount (B) 1,3-butylene glycol 5.00 Purified water Residue (A) The ingredients belonging to (heat) are dissolved (oil phase) and separately.
A component belonging to the component (B) was dissolved by heating (aqueous phase). The aqueous phase was added to the oil phase, the mixture was stirred and emulsified, and then cooled to obtain a vanishing cream base.

Results <Criteria> 3: No pigmentation is observed. 2: Slight pigmentation is observed. 1: Medium pigmentation is observed. 0: No change from control site (no treatment) -1: Stronger pigmentation than the control site (no treatment) is observed. The results are shown in Table 2.

[0040]

[0041]

[0042]

[Prescription example] The following is a prescription example of the present invention. In the prescription examples, the “appropriate amount” means an amount that makes the entire prescription 100% by weight.

<Formulation Example 1> Cream (% by weight) 1. Polyethylene glycol monostearate (40E.0.) 2.00 2. Self-emulsifying glyceryl monostearate 5.00 3. Stearic acid 5.00 4. Behenyl alcohol 1.00 5. Liquid paraffin 10.00 6. Glyceryl trioctanoate 10.00 7. Paraoxybenzoic acid ester 0.20 8.1,3-butylene glycol 5.00 9. Disodium edetate 0.01 10. Kojic acid 1.00 11. Acerola (water extract) 0.01 12. Ginkgo (water extract) 0.05 13. Purified water Proper amount Manufacturing method A. Heat 1 to 6 to dissolve. B. 7 to 13 are heated and dissolved. C. Add B to A, emulsify, stir, and cool. D. After C is cooled, it is filled in a container to be a product after inspection. To inunction usage and dose an appropriate amount on the face.

<Formulation Example 2> Emulsion (wt%) 1. Monostearic acid Polyoxyethylene sorbitan (20E.0.) 2.00 2. Tetraoleic acid Polyoxyethylene sorbit (60E.0.) 0.50 3. 3. Lipophilic glyceryl monostearate 1.00 4. Stearic acid 0.50 5. Behenyl alcohol 0.50 6. Avocado oil 4.00 7. Glyceryl trioctanoate 4.00 8. Paraoxybenzoic acid ester 0.20 9.1,3-butylene glycol 5.00 10. Xanthan gum 0.14 11. Disodium edetate 0.01 12. Kojic acid 4.00 13. Carob (ethanol extract) 5.00 14. Purified water Proper amount Manufacturing method A. Heat 1 to 7 to dissolve. B. Dissolve 8 to 14 by heating. C. Add B to A, emulsify, stir, and cool. D. After C is cooled, it is filled in a container to be a product after inspection. To inunction usage and dose an appropriate amount on the face.

<Formulation Example 3> Lotion (% by weight) 1. Polyoxyethylene hydrogenated castor oil (60E.0.) 8.00 2. Ethanol 15.00 3. Kojic acid glucoside 7.00 4. Ages (water extract) 0.01 5. Geno ginger (water extract) 0.50 6. Paraoxybenzoic acid ester 0.10 7. Citric acid 0.10 8. Sodium citrate 0.30 9.1,3-butylene glycol 4.00 10. Disodium edetate 0.01 11. Purified water Proper amount Manufacturing method A. Stir 1 to 11 uniformly and dissolve. B. A is filled in a container and the product is obtained after the inspection. To inunction usage and dose an appropriate amount on the face.

(Wt%) <Formulation Example 4> Ointment 1. Polyethylene glycol monostearate (40E.0.) 2.00 2. Self-emulsifying glyceryl monostearate 5.00 3. Stearic acid 5.00 4. Behenyl alcohol 1.00 5. Liquid paraffin 10.00 6. Glyceryl trioctanoate 10.00 7. Paraoxybenzoic acid ester 0.20 8.1,3-butylene glycol 5.00 9. Disodium edetate 0.01 10. Kojic acid 1.00 11. Perilla (ethanol extract) 2.00 12. Cinnamon (ethanol extract) 1.00 13. Sweet mayonnaise (ethanol extract) 2.00 14. Purified water Proper amount Manufacturing method A. Heat 1 to 6 to dissolve. B. 7 to 14 are heated and dissolved. C. Add B to A, emulsify, stir, and cool. D. After C is cooled, it is filled in a container to be a product after inspection. To inunction usage and dose an appropriate amount on the face.

<Formulation Example 5> Pap agent (% by weight) 1. Polyacrylic acid 30.00 2. Kojic acid 0.50 3. Thyme (water extract) 0.10 4. Paprika (ethanol extract) 0.04 5. Pip (water extract) 0.01 6. Sodium polyacrylate 7.00 7. Aluminum chloride 0.30 8. Concentrated glycerin 20.00 9. Sorbitan monooleate 1.00 10. Titanium oxide 4.00 11. Purified water Proper amount Manufacturing method A. 1 to 5, 9 and 11 are heated and dissolved. B. Heat 6 to 8 and 10 to dissolve. C. Add B to A, stir evenly, and mix. D. After cooling C, it is applied to a coating agent, and after inspection, it is a product. Usage and dose: Remove the liner and apply to the affected area.

<Formulation Example 6> Bath agent (% by weight) 1. Liquid paraffin 65.00 2. Glycerin di-2-heptyl undecanoate monostearate 5.00 3. Polyoxyethylene (2E.0.) Glycerin monostearate 2.00 4. Polyoxyethylene (9E.0.) Monooleate 2.00 5. Polyoxyethylene (3E.0.) Lauryl ether 5.00 6. Vitamin E 0.20 7. Kojic acid monopalmitate 2.00 8. Orchid (ethanol extract) 5.00 9. Fragrance 1.00 10. Minute amount of dye 11. Ethanol Proper amount production method A. Mix and dissolve 1 to 9. B. Add 10 to 11 and dissolve. C. Add B to A and stir uniformly. D. C was filled in a soft capsule, and a product was obtained after the inspection. Dosage and dosage Put an appropriate amount in the bath and take a bath.

<Formulation Example 7> Essence (% by weight) 1.1% carboxyvinyl polymer solution 10.00 2. Glycerin 20.00 3. Hyaluronic acid 0.50 4. Ethanol 7.00 5. Kojic acid galactoside 3.00 6. Kojic acid 2.00 7. Lupine (water extract) 0.15 8. Acerola (water extract) 0.05 9. Ages (water extract) 2.00 10. Ginkgo (ethanol extract) 0.01 11. Perilla (Ethanol extract) 0.15 12. Purified water Appropriate amount Production method The above components were mixed, uniformly stirred and dissolved to produce essence. To inunction usage and dose an appropriate amount on the face. It was confirmed that each of the external preparations for skin of Formulation Examples 1 to 7 is a preparation having an effect satisfying the object of the present invention.

[0050]

EFFECTS OF THE INVENTION According to the present invention, there is provided a skin external preparation which synergistically enhances the whitening effect of kojic acid and / or a derivative thereof and has a long-lasting effect, and further improves familiarity with the skin and is excellent in usability. To be done.

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Claims (1)

[Claims] 1. Kojic acid and / or a derivative thereof and an extract of a plant selected from the group consisting of acerola, ginkgo, locust bean, ages, ginger ginger, perilla, cinnamon, sweet mayonnaise, thyme, paprika, hip, orchid and lupine. An external preparation for skin, which comprises one or more of