JP2010138154A - External preparation for skin for dealing with aging - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a cosmetic having drabness-ameliorating effects and suitably dealing with aging. <P>SOLUTION: The external preparation for the skin contains [1] a triterpenic acid or a derivative thereof, and [2] a YAC compound having the following characteristics and/or a salt thereof: (1) having λmax at 405-415 nm and 660-670 nm; (2) having a specific<SP>1</SP>H-NMR spectrum; (3) exhibiting a single peak about at 15 min in HPLC analysis under the following conditions: mobile phase: 90% acetonitrile; column: ODS 4.6×250 mm; flow velocity: 1 mL/min; temperature: 40°C; and detection: ultraviolet region of 210 nm; and (4) having a chemical composition formula of C<SB>34</SB>H<SB>40</SB>O<SB>9</SB>, and mass analysis spectrum of 593(M+H). Preferably, the triterpenic acid is selected from ursolic acid, oleanolic acid, asiatic acid and betulic acid. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an external preparation for skin, and more particularly to an external preparation for skin suitable for aging.

  Containing triterpene skeletons such as ursolic acid, oleanolic acid, asiatic acid, and betulinic acid and carboxyl groups in its structure, triterpenic acid has various skin effects such as whitening action and anti-photoaging action, cosmetics, etc. It is known that it is useful as an active ingredient of other skin external preparations (see, for example, Patent Document 1, Patent Document 2, Patent Document 3, and Patent Document 4). However, triterpenic acid has a problem of compatibility with the preparation components of the external preparation for skin, and esterification is studied to improve its solubility. As the ester, in addition to the aliphatic ester, Aromatic esters (for example, see Patent Document 5), phosphate esters (for example, see Patent Document 6) and the like can be preferably exemplified. By such derivatization, the compatibility is remarkably improved and the usability is increasing.

On the other hand, advanced glycation end products (hereinafter sometimes abbreviated as AGEs) play an important role in the skin aging phenomenon, and olive leaf extract, mugwort, and the like are decomposed. It is known that there is an extract of leaf (see, for example, Patent Document 7, Patent Document 8, and Patent Document 9). Among these, the present inventors have refined an active ingredient of AGEs decomposition action in a mugwort extract and have found a YAC compound having the following chemical characteristics. Compounds having such property values are not known in the literature.
<Characteristics of YAC compound>
(1) It has (lambda) max in 405-415 nm and 660-670 nm.
(2) 1H-NMR spectrum shown in FIG.
(3) It has a 13C-NMR spectrum shown in FIG.
(4) In HPLC analysis under the following conditions, a single peak is shown around 15 minutes.
Mobile phase: 90% acetonitrile column: ODS 4.6 × 250 mm
Flow rate: 1 ml / min.
Temperature: 40 ° C
Detection: UV part 210nm
(5) The chemical composition formula is C ₃₄ H ₄₀ O ₉ and the mass spectrometry spectrum is 593 (M + H).

  On the other hand, in cosmetics, “responding to dullness” has become an important issue in recent years. Conventionally, dullness is caused by accumulation of melanin and its distribution pattern (non-uniform distribution of melanin) (see, for example, Patent Document 10), or irregular blood circulation and hemoglobin oxygen saturation caused thereby. There are various theories such as this (for example, see Patent Document 11), but the cause is not clear. In addition, it is clear that dullness is improved slightly by a whitening agent having an inhibitory action on melanin production, but it does not disappear, and there is a complex cause background rather than a single cause. Guessed. Also, it is speculated that there are a wide variety of physiological phenomena included in the word “dullness” due to this predisposition. In addition, the presence of such a dullness creates a negative impression such as “I am tired”, “I am not well”, “I am aging” in the appearance impression of a third party. However, since there is no fundamental solution in skin care, it has been usually dealt with by modifying the appearance impression with makeup cosmetics (for example, Patent Document 12) See). Certainly, means for dealing with changes in appearance impression is also important, but it is also desired to deal with the presence of dullness by skin care, and development of such skin care means has been desired.

JP 2000-302659 A JP 2000-229840 A Japanese translation of PCT publication No. 2002-520375 Special Table 2002-506802 JP 09-143050 A WO / 2006/132033 brochure JP 2001-122758 A JP 2001-108622 A JP 2007-161663 A JP 09-38045 A JP 2008-50316 A JP 2007-291066 A

  The present invention has been made under such circumstances, and an object thereof is to provide a cosmetic having a dullness improving effect.

In view of such a situation, the present inventors have sought for cosmetics having a dullness-improving effect, and as a result of intensive research efforts, 1) triterpenic acid or its derivatives, and 2) the following characteristics: The inventors have found that cosmetics containing a YAC compound and / or a salt thereof have such characteristics, and have completed the invention.
<Characteristics of YAC compound>
(1) It has (lambda) max in 405-415 nm and 660-670 nm.
(2) 1H-NMR spectrum shown in FIG.
(3) It has a 13C-NMR spectrum shown in FIG.
(4) In HPLC analysis under the following conditions, a single peak is shown around 15 minutes.
Mobile phase: 90% acetonitrile column: ODS 4.6 × 250 mm
Flow rate: 1 ml / min.
Temperature: 40 ° C
Detection: UV part 210nm
(5) The chemical composition formula is C ₃₄ H ₄₀ O ₉ and the mass spectrometry spectrum is 593 (M + H).
That is, the present invention is as follows.
<1> A skin external preparation characterized by containing 1) triterpenic acid or a derivative thereof, and 2) a YAC compound and / or a salt thereof having the following characteristics.
<Characteristics of YAC compound>
(1) It has (lambda) max in 405-415 nm and 660-670 nm.
(2) 1H-NMR spectrum shown in FIG.
(3) It has a 13C-NMR spectrum shown in FIG.
(4) In HPLC analysis under the following conditions, a single peak is shown around 15 minutes.
Mobile phase: 90% acetonitrile column: ODS 4.6 × 250 mm
Flow rate: 1 ml / min.
Temperature: 40 ° C
Detection: UV part 210nm
(5) The chemical composition formula is C ₃₄ H ₄₀ O ₉ and the mass spectrometry spectrum is 593 (M + H).
<2> The external preparation for skin according to <1>, wherein the triterpenic acid is selected from ursolic acid, oleanolic acid, asiatic acid and betulinic acid.
<3> The derivative of triterpenic acid is selected from aliphatic or aromatic esters of triterpenic acid, phosphoric esters of triterpenic acid, and salts thereof, <1> or <2 > The external preparation for skin described in>.
<4> The skin external preparation according to any one of <1> to <3>, wherein the YAC compound is contained as an extract of the above-ground part of Asteraceae or Asteraceae.
<5> The content of the YAC compound in the above-ground extract of the Asteraceae Artemisia or Asteraceae Artemisia is 10-6% by mass to 10-2% by mass, according to <4>. The skin external preparation as described.

  ADVANTAGE OF THE INVENTION According to this invention, the cosmetics which have a dullness improvement effect can be provided.

(1) Triterpenic acid or a derivative thereof, which is an essential component of the cosmetics of the present invention The skin external preparation of the present invention requires triterpenic acid or a derivative thereof (including pharmacologically acceptable salts thereof). It is contained as a component. The triterpenic acid can be applied without particular limitation as long as it is used in the field of external preparations for skin such as cosmetics. For example, ursolic acid, oleanolic acid, asiatic acid, betulinic acid And ursolic acid can be particularly preferably exemplified. As the triterpenic acid derivative, a hydrocarbon ester having 1 to 20 carbon atoms of triterpenic acid or a phosphoric ester of triterpenic acid can be preferably exemplified. Examples of the hydrocarbon ester having 1 to 20 carbon atoms include methyl ester, ethyl ester, hexyl ester, cyclohexyl ester, octyl ester, isooctyl ester, lauryl ester, cetyl ester, stearyl ester, isostearyl ester, oleyl ester and the like. Preferred examples thereof include hydrocarbon group esters having an aromatic ring such as aliphatic esters, benzyl esters, and phenethyl esters. Such components can be derived from triterpenic acid according to conventional methods. In the case of a hydrocarbon ester, triterpenic acid is treated with sodium hydride to obtain a sodium salt, and then a halogenated hydrocarbon is added thereto to cause a reaction. The reaction may be performed at room temperature or under reflux conditions for 1 to 12 hours. The phosphate ester of triterpenic acid can be derived from triterpenic acid according to Patent Document 3, for example. Triterpenic acid phosphate is obtained by treating commercially available triterpenic acid with 1 to 3 equivalents of diethyl-N, N-diethyl phosphoramidate in the presence of tetrazole to react with t-butyl hydroperoxide. It can be synthesized by further reacting with trimethylsilyl bromide after forming triterpenic acid methyl phosphate. These salts can be used without particular limitation as long as they are used in skin external preparations, for example, alkali metal salts such as sodium salts and potassium salts, alkaline earth metals such as calcium salts and magnesium salts, Preferred examples include organic amine salts such as ammonium salt, triethylamine salt, triethanolamine salt and monoethanolamine salt, and basic amino acid salts such as lysine salt and alginic acid salt. Such components express an anti-inflammatory action, a melanin production-inhibiting action, an action of promoting the reconstruction of the collagen fiber bundle structure by light irradiation, and the like on the skin. Working together, it has the effect of significantly improving dullness. In particular, among dullness, dullness in which no improvement effect was observed even when treated with a cosmetic containing a melanin production inhibitor such as an ascorbic acid derivative or arbutin is a suitable target for application. Whether cosmetic treatments containing melanin production inhibitors are effective or ineffective can be determined by applying such melanin production inhibitor-containing cosmetics twice a day for 4 weeks, dull and non-dull. When the color difference of the part is 1 or more, it is determined that there is no improvement effect. In order to achieve such a dullness improving effect, the total amount of one or more selected from the ursolic acid, ursolic acid derivatives and salts thereof is 0.001% by mass to 5%. It is preferably contained in an amount of 0.1% by mass, more preferably 0.1% by mass to 3% by mass. This is because if the amount is too small, the above-described effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

(2) YAC compound which is an essential component of the cosmetic of the present invention The YAC compound which is an essential component of the cosmetic of the present invention is characterized by having the following properties.
(Properties)
(1) It has (lambda) max in 405-415 nm and 660-670 nm.
(2) 1H-NMR spectrum shown in FIG.
(3) It has a 13C-NMR spectrum shown in FIG.
(4) In HPLC analysis under the following conditions, a single peak is shown around 15 minutes.
(5) The chemical composition formula is C34H40O9, and the mass spectrometry spectrum is 593 (M + H).
The ultraviolet / visible absorption spectrum of the YAC compound which is an essential component of the cosmetic of the present invention is shown in FIG. From this figure, it is possible to clearly discriminate the feature that λmax exists at 405 to 415 nm and 660 to 670 nm. When the YAC compound which is an essential component of the cosmetic of the present invention is specified, such ultraviolet / visible absorption characteristics are very advantageous. That is, using HPLC equipped with a multi-wavelength detector, analysis was performed at 210 nm absorption, and the absorption at 405 to 415 nm and 660 to 670 nm was confirmed for the peak. The probability of being the YAC compound of the present invention is very high. In this sense, it is an effective confirmation means. The YAC compound of the present invention is present in the nonpolar part of the polar solvent extract. For this reason, it can be concentrated by extracting with a solvent, removing the extraction solvent by concentration under reduced pressure, etc., then separating with ethyl acetate and water, and collecting the ethyl acetate phase. This can be isolated by subjecting it to fractional purification in a chloroform / methanol mixture system using silica gel column chromatography or the like. Whether or not it is isolated can be identified by determining whether or not it is a single peak (retention time around 15 minutes) by HPLC analysis under the following conditions. FIG. 4 shows an analysis example. In this case, the retention time is 14.7 minutes.
(HPLC conditions)
Mobile phase: 90% acetonitrile column: ODS 4.6 × 250 mm
Flow rate: 1 ml / min.
Temperature: 40 ° C
Detection: UV part 210nm
(5) The chemical composition formula is C ₃₄ H ₄₀ O ₉ and the mass spectrometry spectrum is 593 (M + H).

  The YAC compound that is an essential component of the cosmetic of the present invention is a polar solvent, for example, an organic solvent that may contain water, such as methanol, ethanol, isopropyl alcohol, Alcohols such as n-butanol, propylene glycol and 1,3-butanediol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether, isopropyl ether and tetrahydrofuran, halogenated hydrocarbons such as chloroform and dichloromethane, ethyl acetate By extracting with carboxylic acid esters such as methyl formate and nitriles such as acetonitrile, an extract containing the YAC compound can be obtained. As described above, this can be used for liquid-liquid extraction or column chromatography. Spirit It can be isolated and purified by means. As the extraction solvent, a hydrous alcohol is particularly preferred, and a 70 to 90% aqueous ethanol solution is particularly preferred. It is preferable to use the above-ground part for the plant part used for extraction. Prior to extraction, the plant body is preferably subjected to a fragmentation treatment such as chopping or drying and crushing. The extraction can be performed by immersing the plant or the processed product in a solvent for several days at room temperature and for several hours at a temperature near the boiling point.

  The YAC compound thus obtained exhibits a single spot in thin-layer chromatography (developing solution, chloroform: methanol = 95: 5 to 8: 2) using silica gel as a carrier, and exhibits AGE decomposition activity. The AGEs degradation activity can be quantified simply using the strength of the cleavage activity of α-diketone as an index. That is, it is incubated with 1-phenyl-1,2-propanedione, benzoic acid generated by cleavage is quantified by absorbance, and it can be determined that the greater the amount of benzoic acid produced, the higher the AGEs resolution. As an evaluation closer to vivo, there is a method in which AGEs prepared by actually incubating glucose and bovine serum albumin are decomposed, the amount of decomposition is quantified, and the AGEs resolution is quantified using the amount of decomposition as an index. The YAC compound, which is an essential component of the cosmetic composition of the present invention, exhibits a degradation rate of about 40 to 60% in the degradation of α-diketones when AGEs resolution is quantified by such a method. For bovine albumin AGEs, A decomposition rate of about 65 to 80% is exhibited at 10-3 mass%. Utilizing this property, the YAC compound, which is an essential component of the cosmetic of the present invention, can be blended in cosmetics and the like as an AGEs decomposing agent to quickly decompose AGEs generated by light irradiation and prevent this accumulation. . The procedure of these evaluation methods is shown below. In the cosmetic of the present invention, it is considered that such AGE decomposition action is useful for improving dullness, particularly for improving dullness that is difficult to improve with a melanin production inhibitor. In the cosmetic of the present invention, it is preferable that the YAC compound is contained in a dose that clearly expresses the AGE decomposition action.

<Measurement of CC bond cleavage ability of α-diketone>
1 ml of 22 mM 1-phenyl-1,2-propanedion / MeOH + 0.1 M phosphate buffer (PH7.4) and 1 ml of measurement sample were mixed and reacted at 37 ° C. for 10 hours. The amount of benzoic acid was determined by HPLC. Quantify.
(HPLC conditions)
・ Analysis conditions Detector: Ultraviolet absorptiometer (measurement wavelength: 260 nm)
-Column: Tosoh TSK-ODS80TsQA Column temperature: Room temperature-Moving bed: Glacial acetic acid 2 g / acetonitrile 500 ml + edetate di- sodium solution (1 → 250) 500 ml Flow rate: 1 ml / min

<Measurement of glucose-bovine serum albumin AGE resolution>
The materials used are as follows.
AGE-BSA: Glucose and BSA are incubated at 37 ° C. for 12 weeks or more,
PD-10 columns (Amersham Biosciences 17-0851-1) from which excess glucose was removed Primary antibody: Anti-Albumin, Bovine Serum,
Rabbit-Poly ROCKLAND
201-41331 / 20000
Secondary antibody: Goat anti-rabbit IG ghorseradish
peroxidase conjugate Bio RAD
170-6515 1/10000
Substrate: TMB solution Wako 546-01911
(procedure)
100 μl of 10 μg / ml AGE-BSA was added to a type I collagen-coated 96-well microplate (Bio Coat 35 4407), (1.0 μg AGE-BSA / well) was left at 37 ° C. for 4 hours, and then 0.05% Wash three times with Tween20 / PBS (−) (shake on a micromixer at room temperature for 3 minutes), add 100 μl of each concentration sample dissolved in PBS (−), and react at 37 ° C. for 10 hours or more. Then, it wash | cleans 3 times by 0.05% Tween20 / PBS (-), 100 microliters / well of primary antibodies are added to each well, and it leaves still for 30 minutes at room temperature. Wash 3 times with 0.05% Tween20 / PBS (−), add 100 μl / well of secondary antibody, and let stand at room temperature for 30 minutes. Wash 3 times with 0.05% Tween20 / PBS (−), add 100 μl / well of TMB, and react at room temperature for 15 minutes. Add 100 μl / well of 1N HCl, stop the reaction, and measure the absorbance at 450 nm. The amount of AGEs was changed, a calibration curve was drawn, and the amount of residual AGEs was quantified from this calibration curve. The AGEs decomposition rate was calculated by subtracting the remaining AGEs from the added AGEs, dividing by the added AGEs, and multiplying by 100.

  The YAC compound, which is an essential component of the cosmetic of the present invention, is considered to have a reactive substituent such as a hydroxyl group from the NMR data in FIGS. 1 and 2, and is led to a derivative using such a reactive group. I can do it. Such a derivative is a derivative of a YAC compound that is an essential component of the cosmetic of the present invention. Examples of the derivatives of the present invention include reacting alkyl ethers, alkyl esters, acylated products obtained by reacting acyl halides, monoethanolamine, etc., alkylated with a halogenated hydrocarbon such as methyl iodide. Preferred examples include amides that have been prepared. As long as it has AGEs resolution in the above evaluation method, these derivatives belong to the technical scope of the present invention as essential components of the cosmetic of the present invention.

(3) Cosmetics of this invention The cosmetics of this invention contain the said essential component, and are applied suitably for the dullness which the dullness, especially, the improvement by a melanin production inhibitor is not enough. Preferred examples of such cosmetics include lotions such as cosmetics, emulsions, essences, creams, pack cosmetics, facial cleansing cosmetics, cleansing cosmetics and the like. Furthermore, the dosage form is not particularly limited as long as it is known in the cosmetics field, and is preferably exemplified for lotion preparations, oil-in-water emulsion preparations, water-in-oil emulsion preparations, composite emulsion emulsion preparations and the like. it can. In the composite emulsion dosage form, an aqueous phase is a continuous phase and a W / O / W dosage form in which a water-in-oil emulsion is dispersed therein, and an O / W in which an oil phase is a continuous phase and an oil-in-water emulsion is dispersed therein. / O emulsifier type, mixed system of these and water-in-oil emulsifier type, mixed system of these and oil-in-water emulsifier type, and any of these are applicable. Particularly preferred is a system in which an aqueous phase exists in the outer phase, and a mixed system of a W / O / W dosage form or a W / O / W dosage form and an oil-in-water emulsifier form is particularly preferred. The water-in-oil emulsifier form which is the core of these emulsions is particularly preferably a water-in-oil emulsifier form using an organically modified clay mineral such as distearyldimonium chloride modified hectorite. In such a complex emulsifier type, the strength of the interface is required, and it is preferable to contain an ester of acylglutamic acid in order to increase the strength of the interface on the oil phase side. As an ester of this acyl glutamic acid, for example, “El Dew (registered trademark)” series manufactured by Ajinomoto Co., Inc. can be suitably exemplified. The "Eldu" series includes CL-301 (di-N-lauroyl glutamate (cholesteryl behenyl octyldodecyl)), CL-202 (di-N-lauroyl glutamate (cholesteryl octyldodecyl)), PS-203 (N-lauroyl). There exist di-glutamate (phytosteryl octyldodecyl)), PS-304 (di-N-lauroyl glutamate (phytosteryl behenyl octyldodecyl)) and the like. Any of these can be used, but those which are liquid and viscous are preferred, and in this respect, N-lauroyl glutamate (phytosteryl octyldodecyl) is particularly preferred. In order for this component to exert the effect of strengthening the interface in the composite emulsion system, it is preferable to contain 1 to 10% by mass, and 3 to 7% by mass of the component with respect to the total amount of the cosmetic. Particularly preferred. If it is less than this, there are cases where the effect is not achieved, and if it is too much, there are cases where the strength of the interface is lowered.

  In the cosmetic of the present invention, in addition to such components, optional components that are usually used in external preparations for skin can be contained. Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, palm oil, palm oil, liquid Lanolin, hydrogenated palm oil, hydrogenated oil, molasses, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax and other oils, waxes; liquid paraffin, squalane, pristane, ozokerite, Hydrocarbons such as paraffin, ceresin, petrolatum, microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol -Le, Isosteari Higher alcohols such as alcohol, behenyl alcohol, octyl decanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, sebacic acid Di-2-ethylhexyl, cetyl lactate, diisostearyl malate, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate Synthetic ester oils such as trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, methylphenylpoly Chain polysiloxanes such as Loxane and diphenylpolysiloxane; Cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; Amino-modified polysiloxane, polyether-modified polysiloxane, and alkyl-modified polysiloxane , Oil agents such as silicone oils such as modified polysiloxane such as fluorine-modified polysiloxane; anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine alkyl sulfate ; Cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imida) Zolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), and amphoteric surfactants such as acylmethyltaurine; sorbitan fatty acid esters (sorbitan) Monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hardened castor oil derivatives, glycerin alkyl ether POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-sorbitol monolaurate, etc.), POE glycerin fatty acid ester Tells (POE-glycerol monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil, Non-ionic surfactants such as hydrogenated castor oil derivatives (POE castor oil, POE hydrogenated castor oil, etc.), sucrose fatty acid ester, alkyl glucoside; polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol , Sorbitol, xylitol, maltitol, propylene Ricol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1,2-octanediol, etc. Moisturizing ingredients such as sodium pyrrolidone carboxylate, lactic acid, sodium lactate; surface treated mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic anhydride (Silica), powders such as aluminum oxide and barium sulfate; inorganic pigments such as bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide, which may be treated on the surface PAR; agents whose surface may be treated, such as titanium mica, fish phosphorus foil, bismuth oxychloride; red 202 which may be laked, red Color 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue 1 No., green 201, purple 201, red 204, etc .; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; paraaminobenzoic acid UV absorbers; Anthranilic acid UV absorbers; salicylic acid UV absorbers; cinnamic acid UV absorbers; benzophenone UV absorbers; sugar UV absorbers; 2- (2′-hydroxy-5′-t-octylphenyl) UV absorbers such as benzotriazole and 4-methoxy-4'-t-butyldibenzoylmethane; lower grades such as ethanol and isopropanol Alcohols; vitamin A or derivatives thereof, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or derivatives thereof, vitamin B such as vitamin B12, vitamin B15 or derivatives thereof; α-tocopherol , Β-tocopherol, γ-tocopherol, vitamin E such as vitamin E acetate, vitamin D, vitamin H, pantothenic acid, panthetin, vitamins such as pyrroloquinoline quinone, etc .; phenoxyethanol, etc. Preferred examples of the antibacterial agent include organic modified clay minerals such as hectorite and dimethyl distearyl ammonium modified hectorite. The cosmetic of the present invention can be produced by treating these essential components and optional components according to a conventional method.

  Hereinafter, the present invention will be described in more detail with reference to examples.

<Production Example 1>
After chopping 100 g of dry matter of the whole plant of Artemisia genus Artemisia, 500 ml of methanol is added and heated to reflux for 3 hours. After cooling, insolubles are removed by filtration, followed by concentration under reduced pressure, followed by freezing. The extract 1 was obtained by drying. Thereafter, 200 ml of water and 200 ml of ethyl acetate were added to Extract 1 to perform liquid-liquid extraction, and the ethyl acetate phase was collected and concentrated under reduced pressure to obtain Fraction 1. Fraction 1 was concentrated under reduced pressure and then purified by silica gel column chromatography. That is, the silica gel is wetted with chloroform, packed in a column, and the concentrate of the extract 2 dissolved in chloroform is charged. Chloroform, chloroform containing 1% methanol, chloroform containing 5% methanol, chloroform containing 10% methanol and then 15% 50 ml of methanol-containing chloroform was allowed to flow, and the effluent was concentrated under reduced pressure. These fractions were sequentially designated as Fraction 2, Fraction 3, Fraction 4, Fraction 5, and Fraction 6. When the cleavage activity of α-diketone was examined for fractions 1 to 6, fraction 3 was the highest and was 48%. Fraction 3 was further purified four times by silica gel column chromatography using a chloroform / methanol mixture as an elution solvent (first time chloroform: methanol = 100: 0 → 1: 1, second time chloroform: methanol = 100: 2 → 9). 1: 3rd chloroform: methanol = 100: 5 → 8: 2, 4th chloroform: methanol = 100: 0 → 100: 5), silica gel thin layer chromatography (developing solvent chloroform: methanol = 95: 5), Amorphous fraction 7 as a single spot was obtained by coloration by baking with 50% sulfuric acid aqueous solution. The NMR of this product is shown in FIGS. A chart on HPLC (conditions are as follows) is shown in FIG. The ultraviolet absorption spectrum is shown in FIG. From these results, although the structure itself is unknown, it is presumed that the fraction 7 is a single substance.

<Measurement of glucose-bovine serum albumin AGE resolution of fraction 7>
The AGEs degradation action at various concentrations of Fraction 7 against AGEs previously produced from glucose and bovine serum albumin by the above procedure was measured. The results are shown as a graph in FIG. From this, it can be seen that the presence of 10-5% by mass of the compound of the present invention in fraction 7 exhibits the effectiveness of its AGE decomposition. Further, when the compound of fraction 7 is contained as an extract of a plant body of a plant such as mugwort or a purified product thereof, whether or not the AGEs are decomposed at the blending concentration in the extract or the purified product. If AGEs decomposition action is confirmed, simple identification is made so that the extract or the purified product can be contained in cosmetics, and the content in cosmetics is determined. You can also

<Manufacture of cosmetics>
Using the fraction 7 of the extract of Artemisia genus Artemisia, the cosmetics of the present invention were produced according to the formulation shown below. That is, each of the ingredients i, b, and c is heated to 80 ° C., and b is gradually added to a while stirring to form a primary emulsified oil-in-water emulsion. In addition, secondary emulsification was performed to form a water-in-oil-in-water emulsifier form. This was stirred and cooled to obtain Cosmetic 1 as the cosmetic of the present invention. In the same manner, Comparative Example 1 in which fraction 7 was replaced with water, Comparative Example 2 in which potassium ursolate phosphate was replaced, Comparative Example 3 in which potassium ursolate phosphate was replaced with water, and Substitution 7 were replaced. Comparative Example 4 and Control Example 1 in which both fraction 7 and potassium ursolate phosphate were replaced with water were also prepared in the same manner.

（製法）イ、ロを８０℃で加熱溶解させ、非溶解分を良く攪拌して均一に為し、攪拌下イにロを徐々に加えて、乳化を行い、中間油中水乳液１を得た。

(Manufacturing method) A and B are heated and dissolved at 80 ° C., the non-dissolved portion is well stirred to make it uniform, and B is gradually added to A while stirring to emulsify to obtain water-in-oil emulsion 1 It was.

<Evaluation 1>
For cosmetic 1, Comparative Examples 1 to 4, and Control 1, the effect of improving the bear under the eyes was examined as a dullness improving effect. That is, a total of 24 panelists, 4 people in total, gathered a total of 24 people, and with a color difference meter ("Minolta CR400") adjusted with a standard white plate, the color difference between the cheeks and the white plate, The color difference was obtained, and the color difference between the cheek and the bear was calculated from this. Thereafter, an appropriate amount of the sample was administered to the bear part twice a day in the morning and night, and this operation was continued for 6 weeks. Thereafter, the color difference between the cheek and the bear was measured and calculated again. The results are shown in Table 2. This shows that the cosmetic of the present invention is useful for improving dullness of bears and the like.

<Evaluation 2>
One group of 4 panelists treated her half face with cosmetic 1 and the other half face with control 1 twice a day for 20 days, after which cosmetic 1 was duller than control 1 I was asked whether it was excellent in improvement. As a result, all four respondents said that cosmetic 1 was superior, and the evaluation of evaluation 1 was supported.

  A cosmetic 2 was prepared in the same manner as in Example 1 and evaluated by the procedures of Control Example 1 and Evaluation 2. As a result, 2 responded that the cosmetic 2 was superior to Control 1 and the 2 did not know the difference. I answered. From this, it was found that, although the dullness improving effect is recognized in the cosmetic 2, it does not reach the cosmetic 1 and the mugwort extract and the triterpenic acid derivative are preferably contained in the outermost phase.

  A cosmetic 3 was prepared in the same manner as in Example 1 and evaluated by the procedures of Control Example 1 and Evaluation 2. As a result, 2 responded that the cosmetic 3 was superior to Control 1 and the 2 did not know the difference. I answered. From this, it was found that although the dullness improving effect is recognized in the cosmetic 3, it does not reach the cosmetic 1.

  A cosmetic 4 was prepared in the same manner as in Example 1 and evaluated by the procedures of Control Example 1 and Evaluation 2. As a result, 2 responded that the cosmetic 4 was superior to Control 1 and the 2 did not know the difference. I answered. From this, it was found that although the dullness improving effect was recognized in the cosmetic 4, it did not reach the cosmetic 1.

  The present invention can be applied to cosmetics.

FIG. 3 is a diagram showing 1H-NMR of the compound of fraction 7. It is a figure which shows 13 C-NMR of the compound of the fraction 7. It is a figure which shows the HPLC chart of the compound of the fraction 7. It is a figure which shows the ultraviolet absorption spectrum of the compound of the fraction 7. It is a figure which shows the glucose-bovine serum albumin AGE resolution | decomposability of the fraction 7 in manufacture example 1. FIG. It is a figure which shows the mass spectrometry spectrum of the compound of the fraction 7.

Claims (5)

A skin external preparation characterized by comprising 1) triterpenic acid or a derivative thereof, and 2) a YAC compound and / or a salt thereof having the following characteristics.
<Characteristics of YAC compound>
(1) It has (lambda) max in 405-415 nm and 660-670 nm.
(2) 1H-NMR spectrum shown in FIG.
(3) It has a 13C-NMR spectrum shown in FIG.
(4) In HPLC analysis under the following conditions, a single peak is shown around 15 minutes.
Mobile phase: 90% acetonitrile column: ODS 4.6 × 250 mm
Flow rate: 1 ml / min.
Temperature: 40 ° C
Detection: UV part 210nm
(5) The chemical composition formula is C ₃₄ H ₄₀ O ₉ and the mass spectrometry spectrum is 593 (M + H). The external preparation for skin according to claim 1, wherein the triterpenic acid is selected from ursolic acid, oleanolic acid, asiatic acid and betulinic acid. The skin according to claim 1 or 2, wherein the derivative of triterpenic acid is selected from aliphatic or aromatic esters of triterpenic acid, phosphoric esters of triterpenic acid, and salts thereof. Topical agent. The external preparation for skin according to any one of claims 1 to 3, wherein the YAC compound is contained as an extract of the above-ground part of Asteraceae or Asteraceae. 5. The skin according to claim 4, wherein the content of the YAC compound in the above-ground extract of the Asteraceae Artemisia or Asteraceae Artemisia is 10 −6 mass% to 10 −2 mass%. Topical agent.

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