JP3415199B2 - External preparation for skin - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin characterized by containing kojic acid and / or a derivative thereof and an extract of a specific plant as active ingredients. And
More specifically, the present invention relates to a skin external preparation excellent in an effect of synergistically enhancing the cell-proliferating action of kojic acid or a derivative thereof by using a specific plant extract and restoring the elasticity of aged skin. 2. Description of the Related Art Unlike other organs, the skin is in direct contact with the outside world, and is therefore susceptible to such effects. The influence of the outside world includes physical factors such as cold, warm, dry, and sunlight, and chemical factors such as detergents. Among them, the effect of sunlight, especially ultraviolet rays, on the skin is significant. As we age, the skin shows various signs of aging. Increased wrinkles, decreased skin softness, and elasticity are the most typical examples, and the phenomenon is said to be accelerated by ultraviolet rays. Although there are considerable individual differences in the skin aging phenomenon due to ultraviolet rays, in today's dermatology,
Research on the aging of the skin due to sunlight (so-called photo aging) has come to occupy a very important position. [0003] UV light is UV-
C (200 to 280 nm), UV-B (280 to 320 nm), UV-A (320 to 400 nm)
Photoaging is mainly due to UV-A and U
It is thought to be caused by the combined action of VB. Sunscreens containing UV absorbers have been used to protect the skin from these harmful UV rays, but their effects are temporary and have no effect on restoring reduced skin functions. Was. In addition, retinoic acid, which has attracted attention in recent years, is said to be the only effective treatment for photoaging, but has the problem of having large side effects. Kojic acid is
It is a safe drug that has the effect of preventing skin elastic fibrosis (Japanese Patent Application Laid-Open No. 62-5909), but its effect is not always sufficient, and its effect is further enhanced. Was desired. DISCLOSURE OF THE INVENTION [0004] The present invention provides a synergistic enhancement of the cell proliferation effect of kojic acid or a kojic acid derivative by using an extract of a specific plant in combination with the elasticity of aged skin. It is an object of the present invention to provide a novel skin external preparation having an excellent effect of recovery. Means for Solving the Problems The present inventors have made intensive studies to achieve the above object, and as a result, thistle,
A plant selected from the group consisting of arnica, oak, kumabaso, grapefruit, sanshikisumire, jiou, juzdama , soybean , dandelion, tormentula, hamamelis, sunflower, coltsfoot, bakuryo, bramble, matsukasa, mitsugashiwa, murasakisikib, ratania and lettuce. Alternatively, they have found that the combination of two or more kinds with kojic acid and / or a derivative thereof synergistically enhances their pharmacological properties of cell proliferation and wound healing, and completed the present invention. That is, according to the present invention, there is provided a skin external preparation having an excellent anti-aging effect, comprising kojic acid and / or a derivative thereof and a specific plant extract as active ingredients. DETAILED DESCRIPTION OF THE INVENTION Kojic acid (5-oxy-2-oxymethyl-γ-pyrone) used in the present invention includes pure 5-oxy-2-oxymethyl-γ-pyrone, koji A fermentation solution containing kojic acid as a main component obtained by culturing a known strain having an acid-producing ability, a concentrated solution of the fermentation solution, and a product obtained by extracting and crystallizing kojic acid from the fermentation solution are used. You. Examples of the kojic acid derivative include, for example, Japanese Patent Publication No. 60-10005, Japanese Patent Publication No. 1-47452, Japanese Patent Publication No. 3-74229, and Japanese Patent Publication No. 58-221.
51 JP, by coupling a saccharide to 2-position of -CH ₂ OH group of the ester compound and kojic acid kojic acid disclosed in JP-B-58-22152, koji which to stabilize the kojic acid molecule Known compounds such as acid derivatives can be used alone or in combination of two or more.
Examples of the specific plant extract used in combination with kojic acid and / or a derivative thereof include the following. Thistles (Cnicus benedictus) grow on dry sands in the Mediterranean region. The extract (Blessed This
As tle extract, those extracted from roots, leaves, fruits and the like can be suitably used. Arnica (Arnica montana L.) is a plant of the Asteraceae family and grows in mountainous regions such as the Alps, Himalayas and Rockies. As the extract (Arnica Extract), those extracted from flowers and roots can be suitably used. Pterodendron amurense Rupre
cht) has been used as a crude drug since ancient times. It is mainly grown in Hokkaido, Nagano and Gifu prefectures. The extract (Ph
As ellodendron Bark Extract), an extract obtained by extracting purified water, ethanol, propylene glycol, 1,3-butylene glycol or a mixed solution thereof from bark of perilla or other bark of the same genus plant is preferably used. Can be used. [0011] Kurabasou (Asperula odorata) is a plant that normally grows in the wooded areas of central, eastern and southern Europe. As the extract (Woodruff Extract), those extracted from leaves or flowers can be suitably used. Grapefruit Ext
As ract, Citrus Paradisi Extract, a grapefruit (Citrus paradisi (Rutaceae)) fruit that is finely sliced and extracted with a mixed solution of 1,3-butylene glycol and ethanol can be suitably used. Sanshiki violet (Viola tricolor.L.)
Is a one-year or two-year herb native to Europe, and as an extract (Pansy Extract), a leaf extract can be suitably used. [0015] Jiaogu extract (Rehmannia Root Extract)
As for the red pheasant (Rehmannia glutinasa Libosc
hitz var.purpurea Makino) or other congener plants from the roots of ethanol, 1,3-butylene glycol,
An extract obtained by extraction with purified water or a mixture thereof can be suitably used. Juzudama (Coix lacryma-jobi L.var.su)
sutama Honda) is a plant of the same kind as adlay, whose fruit is called river husk and is used as a substitute for yoquinin. As the extract (Job's Tears Extract), an ethanol solution obtained by evaporating an extract obtained by extraction with an ethanol solution to dryness can be suitably used. As a soybean extract, soybean (Glycine ma
x Drying oil (Soy Beam Oil, Soya Oil) obtained from seeds of x Merrill (Leguminosae) can be suitably used. As the dandelion extract, a leaf and root extract of dandelion (Taraxacicum) can be suitably used. [0020] Potentilla tormentilla S
chrk.) is a member of the Rosaceae family and is distributed in Europe. As the Tormentil Extract, a root extract can be suitably used. Hamamelis virginiana L.
Is also known as Witch Hazel, eastern North America, Canada,
It is a deciduous tree that reaches 5 to 10 meters in height in a slightly humid forest in Mexico. Its extract (Hamamelis
As Extract), those extracted from leaves or leaves and bark with purified water, ethanol and 1,3-butylene glycol can be suitably used. As sunflower extract, an extract obtained from sunflower (Helianthus annus L.) can be suitably used. Coltsfoot (Tussilago vulgaris, Tussi)
lago farfafa L.) is a perennial herbaceous plant of the Asteraceae family.
Native to Europe, western and northern Asia, and northern Africa. Its extract (Coltsfoot Extract, Water-soluble Coltsfoot Extract)
As Extract), an extract extracted from a flower or a leaf with purified water, propylene glycol, 1,3-butylene glycol or the like can be suitably used. [0025] Matsuhodo (Poria cocos Wolf) is infested by the roots of pine plants and forms an irregular, massive, sclerotium that grows in a fetal size around the roots of pine trees three to four years after cutting.
Bukryo is the outer layer of the sclerotium of Matsuhodo,
It is a slice. Hoeken E
xtract) is an extract obtained by extracting the sclerotium of matsuhod from the outer layer with ethanol, purified water, etc.
Those containing 3-butylene glycol can be suitably used. [0025] Bramble (Rubi fructiosi) is a plant that grows in wasteland, with many thorns on the stem and leaves in the shape of a hand. White flowers bloom and black fruits become. Its extract (Bramble
Extract) is preferably a flower extract. Pine Cone Extract
The extract obtained by extracting pine glycol (Pinus sylyestris L.) cones native to Germany, Russia and northern Europe with propylene glycol, purified water or the like can be suitably used. Honeysuckle (Menyanthes trifoliata L.)
Is a perennial member of the Gentian family native to Ikenuma. The extracts (Bogbean Extract, Buckbean Extract)
A leaf extract can be suitably used. Murasakisikib (Callicarpa japonica Th
unb.) is a deciduous shrub belonging to the family Pectinaceae, and as its extract, those extracted from fruits can be suitably used. [0030] Ratania (Ratanhia payta) is a plant that grows in South America, and its extract (Rhatany Extract) is preferably a root extract. Lettuce extract, Lactuca
Extract) is preferably a transparent liquid obtained by pressing lettuce (Lectuca sativa L.) and concentrated glycerin added thereto, or an extract obtained by extracting leaves with purified water or 1,3-butylene glycol. Can be used for In the present invention, the amounts of the above-mentioned kojic acid and / or a derivative thereof and a plant extract may be the same as those for cosmetics such as creams, lotions, emulsions, packs, lotions, essences, ointments, In any case where it is used as an external preparation such as a poultice or a plaster, the plant extract contains 0.0001 to 20% by weight, preferably 0.01 to 10% by weight, of kojic acid and / or Or 0.001 to 10% by weight of a derivative thereof,
Preferably, it is blended in the range of 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 described above, for example, cataplasms, frusters, pastes, creams,
Ointments, aerosols, emulsions, lotions, emulsions, essences, packs, gels, powders, foundations,
It is widely used in known forms as pharmaceuticals such as sun care and bath salt, quasi-drugs, and cosmetics. In preparing the external preparation of the present invention, various known active ingredients usually used, for example, carpronium chloride, cepharanthin, vitamin E, vitamin E nicotinate, nicotinic acid, nicotinamide, benzyl nicotinate, and shochu Peripheral vasodilators such as tincture and pepper tincture, refreshing agents such as camphor and menthol, antibacterial agents such as hinokitiol, benzalkonium chloride, undecylenic acid, anti-inflammatory agents such as lysozyme chloride, glycyrrhizin, allantoin, ascorbic acid, arbutin, etc. Various extracts derived from animals, plants, and microorganisms, such as a whitening agent, a placenta extract, a liver extract, and a lactic acid bacteria culture extract, can be appropriately added and used. The above-mentioned pharmaceuticals, quasi-drugs, and cosmetics include known active ingredients, base agents such as surfactants and fats and oils, and, if necessary, known humectants, preservatives, and antioxidants. Agents, UV absorbers / scatterers, chelating agents, pH adjusters,
Various additives such as fragrances and coloring agents can be used in combination. The following are examples and test examples of their effects, which do not limit the present invention in any way. <Test 1 Example 1> Skin Cell Proliferation Action A human skin tissue was sliced, attached to the bottom of a cell culture dish, and Eagle's MEM culture solution (containing 10% calf serum).
And cultivate for one week. The fibroblasts whose bottoms are almost completely filled with the petri dish are treated with a 0.25% trypsin solution to form single cells, and then 10000 cells /
Make a culture solution of 0.1 ml and add this solution
ml of Eagle's MEM culture medium and the samples shown in Table 1 were further added, and cultured in a CO ₂ -incubator for 2 weeks. After cell fixation and staining, cell colonies were counted (no sample was added). The case was the control). In this test, a plant extract obtained by adding 100 ml of a solvent to 10 g of the original plant, stirring at room temperature for 3 hours, and evaporating to dryness was used. Table 1 shows the results. The colony formation rate was calculated by the following equation. [0039] [0040] [0041] [0042] [0043] [0044] <Test Example 2> Skin Elastic Fibrosis Preventive Effect Sprague-Dawley female rats, 4 weeks old, were used in groups of 10 rats each, and the efficacy shown in Table 2 was applied to the back of each rat. Ingredients (Plant extract: 10 g of original plant and solvent 1
After adding 00 ml and stirring at room temperature for 3 hours, the mixture was evaporated to dryness. ) Is applied with a drug suspended in a 1% aqueous solution of carboxymethyl cellulose. As a control, only a 1% carboxymethylcellulose aqueous solution is applied. One hour after application, the coating solution was wiped with warm water, and Toshiba 20S: E30
Using four UV tubes, 62cm behind the test rat
Irradiation from a distance of 20 minutes. Perform this operation three times a week (monthly,
Wednesday, Friday) and keep this for 6 months. On the day when ultraviolet irradiation was not performed, the operation of applying the agent of the present invention and the control solution was performed. After the above-described UV irradiation, only the coating operation was continued for another 6 months. After the above test (1
Two months later), the tissues of the test rats were sampled from the drug-applied section and the control section, paraffin sections of the skin were prepared, hemotoxylin-eosin (H & E) staining, Weigert (Weiger).
t) Staining and Orcein-Giemsa staining were performed to observe the state of elastic fibers according to the following criteria.
Shown in Judgment Criteria- : No elastic fibrosis clot ±: Very slight elastic fibrosis clot observed +: Mild elastic fibrosis clot observed ++: Moderate elastic fibrosis clot observed +++: Severe elasticity A fibrosis mass is recognized. [0050] [0051] [0052] Formulation Examples The formulation examples of the present invention are described below. In the formula examples, "appropriate amount" means that the entire formula becomes 100% by weight. <Formulation Example 1> Cream (% by weight) 1. Polyethylene glycol monostearate (40E.0) 2.00 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. Paraoxybenzoate 0.20 8.1 1,3-butylene glycol 5.00 9. Disodium edetate 0.01 10. Kojic acid 1.00 11. Thistle (water extract) 0.50 Arnica (water extract) 0.10 13. Purified water qs production method A. Heat and dissolve 1-6. B. Heat and dissolve 7-13. C. Add B to A, emulsify, stir and cool. D. After cooling, C is filled into a container, and is used as a product after inspection. Directions and dosage Apply appropriate amount to face. <Formulation Example 2> Emulsion (% by weight) 1. Polyoxyethylene sorbitan monostearate (20E.0.) 2.00 2. Polyoxyethylene sorbite tetraoleate (60E.0.) 0.50 3. Lipophilic glyceryl monostearate 1.00 Stearic acid 0.50 5. Behenyl alcohol 0.50 6. Avocado oil 4.00 7. Glyceryl trioctanoate 4.00 8. Paraoxybenzoate 0.20 9.1 1,3-butylene glycol 5.00 10. Xanthan gum 0.14 11. 11. Disodium edetate 0.01 Kojic acid 4.00 13. Oak (ethanol extract) 5.00 14. Purified water qs production method A. Heat and dissolve 1 to 7. B. Heat and dissolve 8-14. C. Add B to A, emulsify, stir and cool. D. After cooling, C is filled into a container, and is used as a product after inspection. Directions and dosage Apply appropriate amount to face. <Formulation Example 3> Lotion (% by weight) Polyoxyethylene hydrogenated castor oil (60E.0.) 8.00 2. 2. Ethanol 15.00 Kojic acid glucoside 7.00 4. 4. Kurabaso (ethanol extract) 2.00 Grapefruit (1,3-butylene glycol extract) 0.50 6. 6. Paraoxybenzoic acid ester 0.10 7. citric acid 0.10 Sodium citrate 0.30 9.1,3-butylene glycol 4.00 10. 10. Disodium edetate 0.01 Purified water qs production method A. 1 to 11 are uniformly stirred and dissolved. B. A is filled in a container, and is used as a product after inspection. Directions and dosage Apply appropriate amount to face. <Formulation Example 4 > Bath agent (% by weight) Liquid paraffin 65.00 2. 2. Glycerin monostearate di-2-heptylundecanoate 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 Vitamin E 0.20 7. 7. Kojic acid monopalmitate 2.00 8. Dandelion (water extract) 3.00 Perfume 1.00 10. Dye fine amount 11. Ethanol qs production method A. 1 to 9 are mixed and dissolved. B. Add 10 to 11 and dissolve. C. Add B to A and stir uniformly. D. C was filled in a soft capsule to obtain a product after inspection. Usage and dosage Put appropriate amount of water in the bathtub. <Formulation Example 5 > Essence (% by weight) 1.1% Carboxyvinyl polymer solution 10.00 Glycerin 20.00 3. 3. Hyaluronic acid 0.50 Ethanol 7.00 5. 5. Kojic acid galactoside 3.00 6. Kojic acid 2.00 7. Tormentula (ethanol extract) 1.00 Hamamelis (1: 1 mixed extract of water and ethanol) 0.20 9. 10. Sunflower (ethanol extract) 0.10 Coltsfoot (1: 1 mixture extract of water and propylene glycol) 0.10 11. Bukuro (water extract) 0.01 12. Purified Water Proper Production Method The above components were mixed, uniformly stirred and dissolved to produce an essence. Directions and dosage Apply appropriate amount to face. It was confirmed that each of the skin external preparations of Formulation Examples 1 to 5 was a preparation having an effect satisfying the object of the present invention. According to the present invention, the kojic acid and / or a derivative thereof have an effect of synergistically enhancing the cell proliferation effect and restoring the elasticity of aged skin in addition to the inherent fairness effect of kojic acid and / or its derivative. An excellent skin external preparation is provided.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI A61K 35/78 A61K 35/78 X (56) References JP-A-6-128138 (JP, A) JP-A-2-28105 ( JP, A) JP-A-3-188011 (JP, A) JP-A-3-193712 (JP, A) JP-A-3-236306 (JP, A) JP-A-3-236322 (JP, A) JP JP-A-3-190809 (JP, A) JP-A-2-49714 (JP, A) JP-A-5-39484 (JP, A) JP-A-3-236320 (JP, A) JP-A-3-188008 (JP JP-A-4-334308 (JP, A) JP-A-4-235113 (JP, A) JP-A-4-313213 (JP, A) JP-A-4-82837 (JP, A) 1-2242509 (JP, A) JP-A-60-258104 (JP, A) JP-A-57-209208 (JP, A) JP-A-63-57510 JP, A) JP-A-61-50909 (JP, A) JP-A-57-209209 (JP, A) JP-A-52-156936 (JP, A) JP-A-1-83008 (JP, A) JP-A-57-54110 (JP, A) JP-A-60-78910 (JP, A) JP-A-7-61915 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 7 / 00-7/50

Claims (1)

(57) [Claims] [Claim 1] Kojic acid and / or a derivative thereof, thistle, arnica, oubaku, kumabaso, grapefruit, sanshikisumire, jiou, juzdama, soybean , dandelion, tolmentula, hamamelis, sunflower, yellowtail An external preparation for the skin, comprising as an active ingredient one or more plant extracts selected from the group consisting of bukuro, bramble, matsukasa, honeywort, murasakisikibu, ratania, and lettuce .