JP5766775B2 - Method for producing skin external preparation suitable for dullness improvement - Google Patents

Description

  The present invention relates to an external preparation for skin such as cosmetics, and more particularly to an external preparation for skin such as cosmetics useful for improving dullness.

  In cosmetics, “dullening” 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 1), or irregular blood circulation and hemoglobin oxygen saturation caused thereby. Although there are various theories such as this (for example, see Patent Document 2), 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” or “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 3). 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.

On the other hand, plants of the genus Gentianaceae are used in folk remedies as herbal medicines, which are dried whole flowers in the flowering period, for the purpose of suppressing abdominal pain, promoting digestion, and increasing appetite. In addition, the extract is used for the purpose of promoting blood circulation (for example, see Patent Document 4) or promoting hair growth (for example, see Patent Document 5). However, it is not known at all that an extract of a plant belonging to the genus Gentianaceae has an action of increasing glutathione production in cells. Moreover, the YAC compound and / or its salt which are contained in the Asteraceae mugwort plant having the following characteristics are novel compounds not described in the literature, and of course, their medicinal effects are not known at all. Furthermore, it is not known at all that a combination of these is incorporated into an external preparation for skin to show a remarkable dullness improving effect.
<Characteristics of YAC compound>
(1) It has (lambda) max in 405-415 nm and 660-670 nm.
(2) ¹ H- NMR spectrum shown in FIG.
(3) It has a ¹³ C- 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).

From a different perspective, advanced glycation end products (hereinafter sometimes abbreviated as AGEs) play an important role in the skin aging phenomenon. It is known that there is a product, a mugwort leaf extract, etc. (see, for example, Patent Document 6, Patent Document 7, and Patent Document 8). However, there is no disclosure or suggestion of a technique for combining an AGEs degrading agent with an extract of a plant belonging to the genus Gentianaceae. The possibility of combining the extract of mugwort and the extract of the plant of the genus genus in the cosmetic is disclosed for its possibility (see, for example, Patent Document 9), but the combination of the actual combination Is not done at all.

JP 09-38045 A JP 2008-50316 A JP 2007-291066 A JP-A-2005-336116 JP 2005-272432 A JP 2001-122758 A JP 2001-108622 A JP 2007-161663 A JP 2004-35440 A

  The present invention has been made under such circumstances, and an object of the present invention is to provide means corresponding to the presence of dullness by skin care.

In view of such a situation, the present inventors have sought for means corresponding to the presence of dullness by skin care, and as a result of intensive research efforts, 1) an extract of a plant belonging to the genus Gentianaceae and 2) It has been found that an external preparation for skin containing a YAC compound having the following characteristics and / or a salt thereof has such an action, and has completed the invention.
<Characteristics of YAC compound>
(1) It has (lambda) max in 405-415 nm and 660-670 nm.
(2) ¹ H- NMR spectrum shown in FIG.
(3) It has a ¹³ C- 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
That is, the present invention is as follows.
<1> An external preparation for skin, comprising 1) an extract of a plant belonging to the genus Gentianaceae 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) ¹ H- NMR spectrum shown in FIG.
(3) It has a ¹³ C- 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> An extract of a plant belonging to the genus Gentianaceae, when the human liver cancer-derived cell line HepG2 is cultured in the presence of the extract at a concentration of 20 μg / mL, compared to the absence thereof , The external preparation for skin according to <1>, which has an action of increasing the production amount of glutathione by at least 40% .
<3> The external preparation for skin according to <1> or <2>, which is a complex emulsifier type.
<4> The composite emulsifier form is a dosage form in which an aqueous phase is a continuous phase and oil droplets and water-in-oil emulsified droplets are dispersed in the continuous phase. Skin external preparation.
<5> 1) Oil phase of water-in-oil emulsified droplets in which an extract of a plant belonging to the genus Gentianaceae and 2) a YAC compound and / or a salt thereof having the following characteristics are dispersed in an aqueous phase. The external preparation for skin according to <4>, characterized in that it is contained therein.

  According to the present invention, means corresponding to the presence of dullness itself can be provided by skin care.

It is a figure which shows < ¹ > H- NMR of a YAC compound. It is a figure which shows ¹³ C- NMR of a YAC compound. It is a figure which shows the HPLC chart of a YAC compound. It is a figure which shows the ultraviolet absorption spectrum of a YAC compound. It is a figure which shows the mass spectrometry spectrum of the compound of YAC. It is a figure which shows the measurement result of the glucose-bovine serum albumin AGE decomposition | disassembly effect | action of a YAC compound.

<1> Extract of assembly which is an essential component of the external preparation for skin of the present invention The external preparation for skin of the present invention is characterized by containing an extract of a plant belonging to the genus Gentianaceae as an essential component. Preferred examples of the plant belonging to the genus Gentianaceae include assembly or murrex. To create an extract from such a plant, add 1 to 50 mass times of solvent to the plant subjected to processing such as drying, shredding, pulverization, etc., and if necessary, add extraction promotion measures such as stirring, homogenate, Soak for several days at room temperature, or for several hours at temperatures near the boiling point, remove insolubles by filtration, etc., if necessary, perform vacuum distillation, freeze drying, etc. In addition, it can be contained in a skin external preparation. The whole plant is preferably used as the plant part to be used, and the flowering period is preferred as the plant collection period. At this time, as an index of whether or not it can be contained in an external preparation for skin, it can be used whether or not the production of glutathione can be promoted with respect to the human liver cancer-derived cell line HepG2. That is, when the effect on the production of glutathione is measured according to the following procedure and the production promotion value (the amount of glutathione produced in the presence of the sample / the amount of glutathione produced in the absence of the sample) is 1.4 or more Is determined to be contained, and when it is 1.5 or more, it is determined that it is more preferable. In the external preparation for skin of the present invention, an extract of a plant belonging to the genus Sembli determined to be suitable for such inclusion is preferably contained in an amount of 0.001 to 1% by mass, more preferably 0.01 to 0.1% by mass. To do. Such production promotion of glutathione works with a YAC compound described later to promote improvement of dullness.

<Procedure>
A measurement test of glutathione production was performed using a human liver cancer-derived cell line HepG2 (ATCC; CRL-11997). Cells were suspended in RPMI 1640 medium (GIBCO) containing 10% by volume fetal calf serum (GIBCO), seeded on a culture plate, and 37 ° C in a CO ₂ incubator (95% by volume air, 5% by volume carbon dioxide). The cells were cultured for 24 hours under the above conditions. After culturing for 24 hours, each extract suspended in dimethyl sulfoxide was replaced with a sample-added medium containing 20 μg / ml in the medium as a dry solid amount, and further cultured for 24 hours.
The cells were collected and then frozen and thawed at −30 ° C. to disrupt the cells and elute intracellular glutathione. The sample was centrifuged at 1000 × g for 15 minutes at 20 ° C., and the supernatant was used as a measurement sample. The amount of glutathione was measured by the DTNB method using a GSH / GSSG-412 kit (manufactured by OXIS Research). That is, 200 μL of glutathione standard, blank, and measurement sample were placed in each cuvette, 200 μL of chromogen and 200 μL of enzyme solution included in the kit were added to each cuvette, and incubated at room temperature for 5 minutes. Thereafter, 200 μL of NADPH solution attached to the kit was added to each cuvette, and the change in absorbance at 412 nm was measured for 3 minutes. The amount of glutathione was calculated from a calibration curve prepared with a glutathione standard set at the same time.

<Production example>
Gentian family genus assembly was collected at the flowering stage, and the whole plant was dried, then chopped with a mixer, and 100 g was weighed. To this was added 500 mL of 50% ethanol aqueous solution, sonicated for 5 minutes, centrifuged (3000 rpm; 5 minutes), the supernatant was filtered and evaporated under reduced pressure, and then 100 mL of water and 100 mL of ethyl acetate were added. Liquid extraction was performed, and the ethyl acetate phase was taken and distilled off under reduced pressure to obtain assembly extract 1. The glutathione production promoting value (the amount of glutathione produced in the presence of the sample / the amount of glutathione produced in the absence of the sample) of this product was 1.69 ± 0.3.
4. In addition, the acceleration value of glutathione production of the extract 2 obtained by distilling off the aqueous phase under reduced pressure (the amount of glutathione produced in the presence of the sample / the amount of glutathione produced in the absence of the sample) is 1.45 ± 0.48. there were.

<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 has the following properties.
(Properties)
(1) It has (lambda) max in 405-415 nm and 660-670 nm.
(2) ¹ H- NMR spectrum shown in FIG.
(3) It has a ¹³ C- 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 C ₃₄ H ₄₀ O ₉ 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 specifying this compound, which is an essential component of the cosmetic of the present invention, 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. 3 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

  The YAC compound which is an essential component of the cosmetic of the present invention is a polar solvent, for example, an organic solvent which 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, It exhibits a decomposition rate of about 65 to 80% 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. Specifically, it is particularly preferable to contain 10 ⁻⁴ to 10 ⁻² mass%.

<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 layer: Glacial acetic acid 2 g / acetonitrile 500 ml + edetate disodium 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 17-085
1-01) Excluding excess glucose 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 1/10
000
Substrate: TMB solution Wako 546-01911
(procedure)
96-well microplate coated with type I collagen (Bio Coat 35 44
07) was added 100 μl of 10 μg / ml AGE-BSA and (1.0 μg AGE-BSA / well) was allowed to stand at 37 ° C. for 4 hours, and then 0.05% Tween20 / PBS (−
) 3 times (shaking on a micromixer at room temperature for 3 minutes), adding 100 μl of each concentration sample dissolved in PBS (−), and allowing to 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 to stop the reaction,
Measure the absorbance at 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 or a carboxyl group from the NMR data in FIGS. 1 and 2, and is converted to a derivative using such a reactive group. Can be led. 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> External preparation for skin of the present invention The external preparation for skin of the present invention contains the essential components and is in the form of an emulsifier. As the emulsifier form, any of an oil-in-water emulsifier form, a water-in-oil emulsifier form, and a composite emulsifier form can be applied, and a composite emulsifier form is particularly preferable. There are two types of complex emulsifier types: the oil-in-water-in-oil form and the water-in-oil-in-water form, in which the structure of the dispersed droplets of the emulsion itself is complex (dispersed droplet complex type), A phase that is a phase, a phase that is an aqueous phase, and that the dispersed droplets are diversified, such as oil droplets, water-in-oil dispersion or water droplets, oil-in-water dispersion, etc. Therefore, in the external preparation for skin of the present invention, the dispersion droplet diversification type is particularly preferable.

  Dispersed droplet composite type composite emulsifier type skin external preparation is an oil-in-water emulsion composition (continuous phase is oil phase) prepared in advance in a continuous phase, or a water-in-oil emulsion composition (continuous phase is aqueous phase). ) Is gradually added under stirring and then homogenized.

  The dispersion droplet diversification type is prepared by preparing an oil-in-water emulsifier form or a water-in-oil emulsifier form in advance, and adding the water-in-oil emulsion composition or the oil-in-water emulsion composition to this and homogenizing it. I can do it.

The external preparation for skin of the present invention is a dispersion type diversified composite emulsifier type, in which the aqueous phase is a continuous phase, and oil droplets and water-in-oil emulsified droplets are mixed and dispersed therein. preferable. This is because, in such an emulsifier form, the emulsion droplet stabilizing effect of the water-soluble copolymer, which is an essential component of the external preparation for skin of the present invention, is particularly remarkably exhibited.

An organically modified clay that is an essential component in the case of the above-mentioned composite emulsifier form of diversified dispersion droplet type, in which the aqueous phase is a continuous phase and oil droplets and water-in-oil emulsified droplets are mixed and dispersed therein The mineral is preferably contained in water-in-oil emulsified droplets dispersed in an aqueous phase that is a continuous phase. Also, in this case, the oil droplets to be dispersed are added to an aqueous phase containing an alkali and pre-dissolved lecithin hydroxide to add an oil phase containing a fatty acid to form an oil-in-water emulsion composition. It is preferable to add a water-in-oil emulsified composition containing minerals and to homogenize and adjust as desired. By adopting such a form, the emulsified droplets, the interface between the oil droplets and the aqueous phase are strengthened, and the emulsion stability is improved. Moreover, since the water-in-oil emulsified droplets dispersed in the aqueous phase are excellent in percutaneous absorbability, it is preferable that the essential component as an active ingredient is contained therein.

In the external preparation for skin of the present invention, optional components usually used in external preparations for skin can be contained in addition to the above components. 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 coconut oil, hydrogenated oil, molasses, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, 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, octyldodecanol, 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 Oils such as silicone oils such as modified polysiloxanes such as fluorine-modified polysiloxanes; Anionic surfactants such as potassium lauryl sulfate and triethanolamine alkyl sulfate; stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine Cationic surfactants such as oxides; imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc. ), Betaine surfactants (alkylbetaines, amidebetaines, sulfobetaines, 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), hydrogenated 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 esters (POE-glycerin monoisostearate, etc.), POE fatty acid Steals (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 / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), Nonionic surfactants such as sugar fatty acid esters and alkyl glucosides; polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol , Dipropylene glycol, diglycerin, isoprene glyco , 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1,2-octanediol, and other polyhydric alcohols; sodium pyrrolidonecarboxylate, lactic acid, lactic acid Moisturizing ingredients such as sodium; powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, barium sulfate, etc., whose surface may be treated; Bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide inorganic pigments that may be treated on the surface; titanium mica, fish phosphorus that may be treated on the surface Pale agents such as foil and bismuth oxychloride; red 202, red 228, red 226, yellow 4, blue 404, yellow 5 and red 5 which may be laked Organic pigments such as No. 05, Red No. 230, Red No. 223, Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Red No. 204; Organic powders such as 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; UV absorption of 2- (2'-hydroxy-5'-t-octylphenyl) benzotriazole, 4-methoxy-4'-t-butyldibenzoylmethane, etc. Agents: lower alcohols such as ethanol and isopropanol; vitamin A or its derivatives, vitamin B6 hydrochloride, vitamin B6 Vitamin Bs such as lipalmitate, vitamin B6 dioctanoate, vitamin B2 or derivatives thereof, vitamin B12, vitamin B15 or derivatives thereof; α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E Preferred examples include vitamin E such as acetate, vitamin D, vitamin H, pantothenic acid, panthetin, pyrroloquinoline quinone and the like; antibacterial agent such as phenoxyethanol; and clay mineral such as hectorite.

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

[Example 1]
The cosmetic of the present invention was 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 carried out to obtain a diversified dispersion diversification type composite emulsifier type in which oil-in-water / water-in-oil mixed. This was stirred and cooled to obtain Cosmetic 1 as the cosmetic of the present invention. Similarly, Comparative Example 1 in which the YAC compound was replaced with water, Comparative Example 2 in which the assembly extract 1 was replaced with water, and Comparative Example 3 in which the YAC compound and the assembly extract 1 were replaced with water were similarly prepared. did.

（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>
About cosmetics 1 and Comparative Examples 1-3, the improvement effect of the bear under eyes was examined as a dullness improvement effect. In other words, a group of 4 panelists, 16 people in total, gathered a total of 16 people, and with a color difference meter ("Minolta CR400") adjusted with a standard white plate, the color difference between the cheek and the white plate, the bear part under the eyes 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 half-face with cosmetic 1 and the other half-face with Comparative Example 3 twice a day for 20 days. 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.

[Example 2]
The cosmetic 2 was produced in the same manner as the cosmetic 1. When this was evaluated by the method of Comparative Example 3 and Evaluation 2, 3 out of 4 responded that cosmetic 2 was superior, but 1 answered that the difference was unclear. It can be seen that the glutathione production promoting action of the assembly extract is related to dullness improvement, and that the glutathione production promoting value is preferably 1.4 or more.

（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２を得た。

(Production method) A and B are heated and dissolved at 80 ° C., and the undissolved portion is stirred well to make it uniform. It was.

[Example 3]
In the same manner as in Example 1, a cosmetic 3 of the present invention in the form of an oil-in-water simple emulsifier was prepared. When this was evaluated by the method of Comparative Example 3 and Evaluation 2, 3 out of 4 responded that cosmetic 3 was superior, but 1 answered that the difference was unclear. The compounding effect to the water-in-oil emulsified droplets in the complex emulsifier form was confirmed.

  The present invention can be applied to skin external preparations such as cosmetics.

Claims (3)

Confirming that the YAC compound and / or salt thereof has the following properties; and
1) and extract of a plant of gentianaceae swertia, 2) a step of blending the YAC compound and / or a combination of a salt thereof, a process for the preparation of a skin external agent, in the external preparation for skin, The method whose content of the said YAC compound and / or its salt is 10 ^{< -4} > -10-2 mass% of the whole skin external preparation .
<Characteristics of YAC compound>
(1) It has (lambda) max in 405-415 nm and 660-670 nm.
(2) It has the ¹ H-NMR spectrum shown in FIG.
(3) It has a ¹³ C-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). An extract of the plant belonging to the genus Gentianaceae contains glutathione in the presence of the extract at a concentration of 20 μg / mL when cultured with the human hepatoma-derived cell line HepG2 as compared to the absence. The method according to claim 1, which has an effect of increasing the production amount by at least 40%. The method according to claim 1 or 2, wherein the external preparation for skin is in a complex emulsifier form.

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