JP2003292449A - Preparation for external use for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a preparation for external use for skin that shows high antiaging effect and high homeostasis restoration of epidermis in order to cope with the occurrence of wrinkles, freckles caused by extrinsic stress, e.g. aging or ultraviolet rays, the skin symptoms caused by senility, e.g. deterioration of skin elasticity and a variety of skin troubles e.g. skin roughening. <P>SOLUTION: Substances having effective activation actions are screened by using antioxidant effect and effects of activating dermal fibroblast cells and epidermal cells as indexes and the extracts from plants in Delphinium, Consolida and relating thereto have been found to have remarkable antioxidant effect and dermal fibroblast cell activation effect and epidermal cell activation effect. The extracts are added to a preparation for external use for skin to provide preparations for external use for skin having high aging resistance and high homeostasis restoration of epidermis. <P>COPYRIGHT: (C)2004,JPO

Description

Description: TECHNICAL FIELD [0001] The present invention relates to an antioxidant and a cell activator containing an extract of a specific plant as an active ingredient. Further, the present invention relates to an external preparation for skin which is effective for preventing aging and restoring epidermal homeostasis, which contains such an antioxidant and a cell activator as active ingredients. [0002] Skin aging symptoms such as wrinkles and spots caused by external stresses such as aging and ultraviolet rays, and decreased skin elasticity include decreased dermal fibroblast function and reduced matrix fibers. Alternatively, degradation and denaturation are important factors. Therefore, in order to obtain an external preparation for skin that has anti-aging and ameliorating effects on skin, it is necessary to investigate components that have the effect of activating or promoting fibroblasts and those that have an antioxidant effect for eliminating reactive oxygen species. Is being done. [0003] For example, with respect to the activity of stimulating and promoting the proliferation of fibroblasts, loquat extract (Japanese Patent Publication No. 5-127206), α-hydroxyacetic acid (JP-A-5-112422) have been proposed.
JP-A-8-104632), 6-benzylaminopurine (JP-A-7-233037), a specific ribonuclease (JP-A-7-309778), L -Lysyl-L-glycyl-L-histidine (JP-A-7-31)
No. 6192), milk-derived fibroblast growth factor (Japanese Patent Application Laid-Open No. HEI 8-119687), oxidized coenzyme A
(JP-A-8-175961) and the like are disclosed. As for antioxidants, Heterogenes of the family Asteraceae (Japanese Patent Application Laid-Open No. 11-180886) are known, and BHA (butylhydroxyanisole) and BHT
A compounding of a synthetic antioxidant such as (butylhydroxytoluene) or a compounding of vitamin E known as a natural antioxidant can be considered. [0004] In addition, external stresses such as aging and ultraviolet rays cause skin aging as well as signs of aging such as wrinkles. This is an important factor that the homeostasis of the epidermis is deviated by the stress. Is known to be. To solve this problem, polyols of glycerin tow, mucopolysaccharides such as hyaluronic acid, amino acids, organic acids,
Cosmetics containing a humectant such as urea or extracts of animals and plants have been used symptomatically. [0005] However, among the components having the above-mentioned effects, there are problems such as insufficient action effects and poor stability. In some cases, a considerable amount must be contained in order to obtain a significant effect. In addition, those that have undesirable side effects or irritation, or that adversely affect the stability of the preparation, those that are difficult to mix with external preparations in terms of odor or color, and that have difficulty maintaining a certain action and quality There were many things. Among them, many of the ingredients known to improve skin roughness have a temporary moisturizing effect, and very rarely activate the epidermis itself, improving the underlying epidermal condition. It has been desired to develop a skin external preparation having a certain effect, that is, a skin external preparation having an effect of restoring epidermal homeostasis. Accordingly, an object of the present invention is to provide wrinkles caused by external stresses such as aging and ultraviolet rays,
The purpose of the present invention is to provide an external preparation for skin that responds to various skin problems such as skin aging symptoms such as occurrence of spots and decrease in skin elasticity and skin roughness, and the specific effects thereof are anti-aging effects and homeostatic epidermis. It is a sexual recovery effect. [0007] In order to solve the above-mentioned problems, the present inventors have an effective activating effect using an antioxidant effect and an activating effect on dermal fibroblasts and epidermal cells as indices. Material screening was performed. As a result, surprisingly, it has been found that extracts of Ranunculaceae, Rhenaceae and its related plants, have remarkable antioxidant effects and dermal fibroblast and epidermal cell activating effects, and have completed the present invention. [0008] That is, the present invention provides an anti-aging skin external preparation and a skin external preparation for restoring epidermal homeostasis, which contain extracts of Ranunculaceae and related plants, and an antioxidant containing the plant extract as an active ingredient. Agents and cell activators. Hereinafter, the configuration of the present invention will be described in detail. Delphinium and extracts its allied plants of the present invention (hereinafter, delphinium extract) The technology relating to a type of delphinium Daihana Hien grass (D. G
randiflorum L. )) To the extent that the technology relating to the application of the extract to a hair restorer has been disclosed, and it has not been known that the extract of Hienzo has a remarkable antioxidant effect and cell activating effect. .
Further, there has been no known technique concerning the external use of the plant extract as an anti-aging skin preparation and / or a skin preparation for restoring epidermal homeostasis. BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, the genus Hienzo and its related plants include the genus Oenothera ( Delph).
Inium ) and plants classified into the genus Consolida can be used, and more specifically, C. ajacis (L.) Schur./
D. ajacis L .; ), Kouhiensou (D. El
atum L. ), Seribahienso ( D. anthr)
iscifolium Hance), Bruno Ukyo Sui jacuzzi (D. brunonianum Royle),
Gazanhiensou (D. Fargesii Franc
h. ), Shisenhiensou (D. Davidii Fr
anch. ), Shinsuirei Jakka ( D. giral)
dii Diels), Kirin Sui jacuzzi (D. man
atum Hand. -Mazz. ), Kozuratsu ( D. tatsienense France.af)
f. ), Unnansu jakka ( D. yunnanen)
se Franc. ), Ten Hokusui Jakuka ( D.
delavayi Franch. ), D. pogonanthum Hand.-Ma
zz. ) And the previously-mentioned Oba Na Hien Saw (D. G
randiflorum L. ) Etc. are preferably used, but are not limited to these species. These plants are perennials or annuals with upright stems and are distributed mainly in the temperate zone of the Northern Hemisphere. [0011] The extract of the present invention may use any part of flowers, fruits, seeds, leaves, stems, roots, and the like, and also whole plants thereof. [0012] The method for preparing the above-mentioned extract of the Chinese radish used in the present invention will be described below, but it is not limited to these extraction solvents and extraction methods. Examples of the extraction solvent include water, ethanol, methanol, isopropanol, isobutanol, alcohols such as n-hexanol, methylamyl alcohol, 2-ethylbutanol, and n-octyl alcohol, glycerin, ethylene glycol, ethylene glycol monomethyl ether, and ethylene glycol. Monoethyl ether, propylene glycol, propylene glycol monomethyl ether, propylene glycol monoethyl ether, triethylene glycol, 1,3-butylene glycol, polyhydric alcohols such as hexylene glycol or derivatives thereof,
It is selected from polar solvents such as ketones such as acetone, 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. One or two
More than one kind of mixed solvent can be suitably used, and phosphate buffered saline can be used. Or hydrocarbons such as petroleum ether, n-hexane, n-pentane, n-butane, n-octane, cyclohexane, squalane,
One or more mixed solvents selected from low-polar or non-polar solvents such as carbon tetrachloride, chloroform, dichloromethane, trichloroethylene, benzene, and toluene can also be suitably used. Further, one or more supercritical fluids or subcritical fluids such as water, carbon dioxide, ethylene, propylene, ethanol, methanol, and ammonia can also be used. As the extraction method, normal pressure or pressurization,
Under reduced pressure, room temperature, a method of extracting and impregnating in a cooled or heated state, a method of extracting using a distillation method such as steam distillation, a pressing method of obtaining an extract by pressing a plant of the genus Hienomizu, and the like, These methods can be used alone or in combination of two or more. [0014] The extract of Hienzo and its related plants thus obtained can be used as it is, but as long as the effect is not lost, deodorization, decolorization,
A purification operation such as concentration may be added, and further, the fractionated product may be used by column chromatography or the like.
These extracts, their purified products, and fractionated products can be dried by removing the solvent therefrom,
Further, it can be used in a form solubilized in a solvent such as alcohol or in an emulsion form. [0015] By blending the extract of Hienflower, which is an active ingredient for antioxidation and cell activation, with an external preparation for skin, an excellent antiaging effect and an effect of restoring epidermal homeostasis can be exhibited. [0016] The amount of the extract of Hienzo in the external preparation for skin is generally 0.0001% by weight as a dry product.
10.0% by weight, preferably 0.001% by weight
~ 5.0% by weight, more preferably 0.001% by weight
~ 1.0% by weight. Examples of the dosage form of an external preparation for skin containing the extract of Hienzo include emulsions such as creams and emulsions, aqueous cosmetics such as lotions and gel-like cosmetics, and cleaning cosmetics such as soaps and facial cleansing foams. Or a peel-off type or wash-off type pack agent. Raw materials that can be used in combination in such a skin external preparation include oils, humectants, surfactants, thickeners, neutralizing agents, preservatives, powder components, pigments, chelating agents,
Raw materials such as fragrances, ultraviolet absorbers, medicinal agents, whitening agents, bactericides, cell activators other than the present invention, antioxidants other than the present invention, and the like can be used in combination according to the purpose. . As a matter of course, the present invention is not limited to the above-mentioned raw materials that can be used in combination, and can be used in combination with various raw materials as long as the effects of the present invention are not impaired. EXAMPLES Next, a production example of an extract of Hienzo as an antioxidant and a cell activator used in the examples, a test for evaluating the effectiveness, an example as an external preparation for the skin and its effectiveness The present invention will be described in more detail with reference to confirmation tests, but it is needless to say that the technical scope of the present invention is not limited thereto. [Production Example 1] A dried product of the roots and seeds of Japanese radish was pulverized, and 990 g of the dried product was impregnated with a 10% by weight 50% by volume aqueous ethanol solution for one week. Thereafter, the residue was removed by filtration, and the extract was concentrated under reduced pressure and further freeze-dried to obtain 180 g of the extract. [Preparation Example 2] A dried product of Spruce was milled, and 108.0 g of the dried product was 50% by volume of 10 times by weight.
It was impregnated with an aqueous ethanol solution for one week. Thereafter, the residue was removed by filtration, and this was designated as Production Example 2. [Preparation Example 3] A dried product of Helicoverpa oleracea was pulverized, and 126.0 g thereof was crushed by 10% by weight to 50%.
It was impregnated with 1,3-butylene glycol for one week. Thereafter, the residue was removed by filtration, and this was designated as Production Example 3. [Production Example 4] A dried product of celiva hyenzo was pulverized, and 1.02 kg was impregnated with 10 times by weight of n-hexane for one week. Thereafter, the residue was removed by filtration, and the extract was concentrated under reduced pressure and dried to obtain 6.9 g of an extract. [Preparation Example 5] A dried product of P. japonica was crushed and impregnated with 91.0 g of squalane of 10 times by weight for one week. Thereafter, the residue was removed by filtration to obtain Production Example 5. <Evaluation of Antioxidant Effect> 100 μL of a 50% by volume aqueous ethanol solution of Production Example 1 diluted to an arbitrary concentration was added to a 96-well plate. Next, 100 μL of a 0.2 mM stable radical ethanol solution of 1,1-diphenyl-2-picrylhydrazyl (DPPH) was added to a 96-well microplate. After standing at room temperature for 24 hours in a dark place, the absorbance of light having a wavelength of 516 nm derived from DPPH radical was measured. Assuming that the absorbance of Production Example 1 without addition is (A) and the absorbance of only the sample is (B), the radical scavenging rate of Production Example 1 can be expressed by the following equation (1). Radical scavenging rate = [1− (B) / (A)] × 100 Formula (1) Table 1 shows the concentration (IC ₅₀ ) of Production Example 1 required to scavenge DPPH radicals by 50%, obtained from measurement data. It is shown in FIG. As is clear from Table 1, Production Example 1 was 0.054
It was found that 50% of the DPPH radical was eliminated when the concentration was added at 3%, thereby revealing the excellent antioxidant effect of the Chinese quince extract. [Table 1] <Activation of dermal fibroblasts> Normal human dermal fibroblasts were seeded on a 96-well plate at 2.0 × 10 ⁴ cells / well. As a seeding medium, D-MEM (manufactured by Niken Institute of Biomedical Research), a commercially available medium to which 5% fetal bovine serum was added, was used. After culturing for 24 hours, Production Example 1 at an arbitrary concentration
Was replaced with a D-MEM medium containing 1% fetal calf serum, and culturing was further performed for 48 hours. Then, 3- (4,
5-dimethyl-2-thiazolyl) -2,5-diphenyltetrazolium bromide (MTT) at 100 μg / mL
The medium was replaced with the added D-MEM medium and cultured for 2 hours. Formazan generated by opening the tetrazolium ring was extracted with 2-propanol, and the absorbance at 550 nm was measured. At the same time, the absorbance at 650 nm was measured as turbidity, and the dermal fibroblast activation activity was evaluated based on the difference between the two measured values. The results are shown in Table 2 as relative values when the dermal fibroblast activating action in the case where Production Example 1 was not added was taken as 100. As is clear from Table 2, 0.025% by weight to 0.2% by weight.
A clear (1% significant) dermal fibroblast activating action was observed in the concentration range of 10% by weight. [Table 2] <Epidermal cell activating action> Normal human epidermal keratinocytes were prepared in an amount of 2.0 × 10 ⁴ keratinocytes per well.
Seeded in 6-well plates. The seeding medium was KG-, a commercial medium.
2 (manufactured by Kurabo Industries) was used. After culturing for 24 hours, the medium was replaced with a KG-2 medium supplemented with Production Example 1 at an arbitrary concentration, and culturing was further performed for 24 hours. Thereafter, 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyltetrazolium bromide (MTT) was added to 100 g / mL of K.
The medium was replaced with G-2 medium and cultured for 2 hours. Formazan generated by opening the tetrazolium ring was extracted with 2-propanol, and the absorbance at 550 nm was measured. At the same time, the absorbance at 650 nm was measured as turbidity, and the epidermal cell activation was evaluated by the difference between the two measured values. The results are shown in Table 3 as relative values with the epidermal cell activation effect when Production Example 1 was not added as 100. As is clear from Table 3,
In the concentration range of 0.03125% by weight to 0.125% by weight, a clear (1% significant) epidermal cell activating action was observed. [Table 3] Example 1 Lotion (1) Ethanol 10.00 (wt%) (2) Polyoxyethylene hydrogenated castor oil (60EO) 0.30 (3) Hienzo extract (Production Example 2) 0.05 (4) Methyl paraoxybenzoate 0.02 (5) Concentrated glycerin 3.00 (6) 1,3-butylene glycol 1.00 (7) Purified water The remaining production method: (2), (1) 3) and (4) are sequentially added,
Dissolve uniformly to make alcohol phase. This was uniformly mixed with the aqueous phase which was previously added (5) and (6) to (7) and homogenized with stirring. Also,
Comparative Example 1 was prepared by substituting (3) with a 50% by volume aqueous ethanol solution. Example 2 Cream (1) Squalane 10.00 (% by weight) (2) Stearic acid 2.00 (3) Hydrogenated palm kernel oil 0.50 (4) Hydrogenated soybean phospholipid 0.10 (5) Cetanol 3.60 (6) Lipophilic glyceryl monostearate 2.00 (7) Glycerin 10.00 (8) Methyl parahydroxybenzoate 0.10 (9) 1% by weight aqueous solution of carboxyvinyl polymer 15.00 (10) 10% by weight L-arginine aqueous solution 1.00 (11) Hydrangea extract (Production Example 1) 0.20 (12) Purified water Remaining production method: Heat-dissolve the oil phase components of (1) to (6) And 80 ° C
And On the other hand, (7) to (9) and (12) were also set to 80 ° C., and the oil phase was added thereto with stirring, and then (1)
Add 0) and emulsify uniformly with a homogenizer.
After cooling to 30 ° C., (11) was added, mixed and homogenized to prepare Example 2. Further, Comparative Example 2 was prepared by substituting (11) with purified water. Example 3 Emulsion (1) Squalane 5.00 (% by weight) (2) Hienzo extract (Preparation Example 5) 5.00 (3) Methylphenylpolysiloxane 4.00 (4) Hydrogenated palm Kernel oil 0.50 (5) Polyoxyethylene sorbitan monostearate (20EO) 1.30 (6) Sorbitan monostearate 1.00 (7) Glycerin 10.00 (8) Methyl paraoxybenzoate 10 (9) 1% by weight aqueous solution of carboxyvinyl polymer 13.00 (10) 10% by weight aqueous solution of L-arginine 1.10 (11) Purified water Remaining production method: Heat and dissolve the oil phase components of (1) to (6) , 80 ° C
And Meanwhile, (7) to (9) and (11) are also heated to 80 ° C. and added to the oil phase with stirring. Then (1
0) and homogenized with a homogenizer.
It cooled and it was set to Example 3. Further, Comparative Example 3 was prepared by substituting squalane for (2). Example 4 Peel-off type pack (1) Polyvinyl alcohol 10.00 (% by weight) (2) Ethanol 2.00 (3) Purified water 50.00 (4) Polyethylene glycol 1500 1.50 (5) 1,3-butylene glycol 5.00 (6) Methyl paraoxybenzoate 0.10 (7) Hyenne extract (Preparation Example 4) 0.20 (8) Polyoxyethylene hydrogenated castor oil (50 EO) 20 (9) Ethanol 8.00 (10) Purified water Remaining production method: (2) was added to (1) and moistened, (3) at room temperature was added, and the mixture was heated to 80 ° C. while stirring slowly. I do. After confirming that (1) was uniformly dissolved, 50
Cool to ℃, add (4), (5) and stir. (4)
After confirming the dissolution of
Then, an alcohol layer in which (6) to (8) were dissolved and (10) were sequentially added, and the mixture was stirred uniformly to obtain Example 4. Also,
A product prepared by substituting (7) with purified water was used as Comparative Example 4. Example 5 Gel Cosmetic (1) Dipropylene glycol 10.00 (% by weight) (2) 1% by weight aqueous solution of carboxyvinyl polymer 50.00 (3) 10% by weight aqueous solution of potassium hydroxide 00 (4) Methyl paraoxybenzoate 0.10 (5) Hienzo extract (Preparation Example 3) 5.00 (6) Purified water Remaining production method: Add (4) to (1), disperse, heat dissolve, and cool Then, add (2) and (6) and stir uniformly. Next, (3) was added to increase the viscosity, (5) was added, and the mixture was stirred uniformly to obtain Example 5. Also, (5) is changed to 50% by volume 1,3
Comparative Example 5 was prepared by substituting butylene glycol aqueous solution. [Example 6] Face wash (1) myristic acid 24.00 (% by weight) (2) stearic acid 12.00 (3) lipophilic glyceryl monostearate 3.00 (4) concentrated glycerin 15. 00 (5) Purified water 30.00 (6) Potassium hydroxide 7.80 (7) Hydrangea extract (Preparation example 1) 0.15 (8) Purified water Remaining production method: (1), (2), (3) ) And (4) are sequentially weighed and heated to 80 ° C. To this, a solution obtained by dissolving (6) and heating (5) to 80 ° C. is added with slow stirring. After stirring until the mixture became homogeneous, the mixture was cooled to 45 ° C., and (7) and (8) were added. Further, Comparative Example 6 was prepared by substituting (7) with purified water. [Prevention of Wrinkle Formation by Ultraviolet Rays] Five hairless mice were grouped into one group, and each group was subjected to Example 1, Example 2, Example 3, Example 5, Comparative Example 1, Comparative Example 2,
Each of Comparative Example 3 and Comparative Example 5 was applied to the back once a day,
1 J / cm ² / Week Long wavelength ultraviolet (UVA) 5
Irradiation was performed for 0 weeks, and evaluation was performed by scoring according to the criteria shown in Table 4. At this time, a group to which only purified water was applied was targeted. As a result, the average value of each group was calculated, and the relationship with the number of UVA irradiation days was shown in Table 5. [Table 4] [Table 5] As is clear from Table 5, in the control group, the depth of wrinkles formed on the skin reached a medium level when the number of UVA irradiation days exceeded 40 weeks, and after 50 weeks, deep wrinkles were formed. Formation was observed. On the other hand, in Examples 1 and 2 according to the present invention, the formation of fine or slight wrinkles was observed after 50 weeks in Examples 1 and 2, and in Examples 3 and 5, After 50 weeks, the formation of moderate wrinkles was observed in one case, and in the other cases, the formation of fine or slight wrinkles was observed. From the above results, it was found that formation of wrinkles was remarkably suppressed in the group applied with the examples. [Usage Test] A use test was carried out using a skin external preparation (Examples 1 to 5) containing the extract of Hienzo as shown in Production Examples 1 to 5 and Comparative Examples 1 to 5. Was. In the use test, 20 female panelists aged 20 to 40 years were treated as a group, and the subjects were blinded twice a day after washing their face when waking up and immediately before going to bed (Example 4 and Comparative Example 4).
For the use group, once every two days), an appropriate amount of the sample was applied to the face. Before and after the use test, the panelists evaluated the condition of the stratum corneum, the elasticity of the skin using a cute meter, and the evaluation of fine wrinkles by naked eye and photographic judgment. The evaluation of the condition of the stratum corneum was made 30 days after the start of the use test, and the evaluation of skin elasticity and fine wrinkles was made 60 days later, before the use. [Evaluation of the condition of the stratum corneum] A commercially available cellophane tape was stuck to the cheek of the subject in a state where the amount of oil after washing the face was low, and after being held down for a while, peeled off, and stuck to a slide glass to which a fixing agent had been applied in advance. Then, the slide glass is immersed in xylene for 1 hour, and the tape is gently peeled off, and then immersed again in xylene for 1 hour. Thereafter, the slide glass is taken out, air-dried, and then immersed in a 1% gentian violet B aqueous solution for 10 minutes. Then, the slide glass is taken out, washed with water, dried, and sealed with balsam to obtain a horny sample. The obtained keratin specimen was visually observed using a microscope, and the shape, exfoliation density, and number of nucleated cells of keratinocytes were scored based on the standards shown in Tables 6 to 8, respectively. Regarding the exfoliation degree of the stratum corneum, the obtained image of the stratum corneum was taken into a computer and scored as follows using image analysis software. [0044] portion and the area S of the occupied corneocytes captured as an image, the area S _n of overlapping portions of n pieces of stratum corneum, determined using image analysis software. The multiplicity of stratum corneum exfoliation was calculated from this value using the following formula (2), and the obtained value of the multiplicity of stratum corneum was scored based on the criteria shown in Table 9. Exfoliation multiplicity = Σn · S _n / S (2) [Table 7] [Table 8] Table 9 Evaluation of multiplicity of exfoliation of keratinocytes In comparison with the total value of the state scores of the stratum corneum prepared before the test, evaluation was made in three stages of “improvement”, “slight improvement”, and “no change”, and the state of the epidermis was determined. Changes in the skin elasticity and fine wrinkle state were also evaluated on a three-point scale of “improvement”, “slight improvement”, and “no change”. The results are summarized in Table 10 below. [Table 10] From the above results, it was clarified that the skin external preparation containing the Chinese quince extract remarkably improved the condition of the epidermis and the stratum corneum, and had a high antiaging effect. Further, during this use test period, Examples 1 to 5 were used.
The effects on the skin due to the continuous use of were observed, but none of the groups using any of the examples complained of skin irritation such as pain or itchiness or skin disorders such as allergic reaction. Further, various abuse tests were attempted to confirm the stability of the preparation, but no deterioration in the quality of the cosmetic such as sedimentation, separation and deterioration of the components was found. According to the present invention, an antioxidant and a cell activator having excellent effects can be provided. Furthermore, by adding this to an external preparation, it can cope with various troubles of the skin such as skin aging symptoms such as wrinkles, occurrence of spots caused by external stress such as aging and ultraviolet rays, decreased skin elasticity, and rough skin, anti-aging. It is possible to provide a skin external preparation excellent in the effect and the effect of restoring epidermal homeostasis.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) A61P 17/16 A61P 17/16 43/00 105 43/00 105 (72) Inventor Aki Ijiri Aki Kobe, Hyogo Prefecture 6-13-13 Minatojima-Nakamachi, Chuo-ku Noevir Kobe Main Office (72) Inventor Keiichi Iriyama 6-13-13 Minatojima-Nakamachi, Chuo-ku, Kobe-shi, Hyogo Noevir Kobe Main Office (72) Inventor Ritsuko Koshimizu 6-13-13 Minatojima-Nakamachi, Chuo-ku, Kobe City, Hyogo Prefecture Noevir Kobe Main Office (72) Inventor Akinori Hanano 6-13-13, Minatojima-Nakamachi, Chuo-ku, Kobe City, Hyogo Prefecture No.1 Kobe Main Office F-term ( Reference) 4C083 AA111 AA112 AA122 AB032 AC022 AC072 AC102 AC122 AC242 AC392 AC432 AC442 AC482 AC582 AD042 AD092 AD152 AD572 CC02 CC04 CC0 5 CC07 DD27 DD31 DD41 EE12 4C088 AB32 CA03 MA63 NA14 ZA89 ZA91 ZB22

Claims (1)

Claims: 1. An external preparation for skin containing one or two or more extracts of Ranunculaceae and its related plants.