WO2011158331A1

WO2011158331A1 - Composition containing zederone in stable state

Info

Publication number: WO2011158331A1
Application number: PCT/JP2010/060131
Authority: WO
Inventors: 一博末次; 哲史森田; 泰弘山田
Original assignee: 株式会社ナリス化粧品
Priority date: 2010-06-15
Filing date: 2010-06-15
Publication date: 2011-12-22
Also published as: JPWO2011158331A1; JP5701872B2

Abstract

The present invention provides a composition that contains zederone in a stable state. More specifically, provided is a composition containing: zederone; one or more components selected from a group consisting of skin-whitening agents, chelating agents, antioxidants, polyphenols, plant extracts, antiseptics, vitamins, UV-absorbing agents, 1,2-octanediols, and 2-ethylhexyl glyceryl ethers; and optionally, a solvent for facilitating the dissolution of the components. The composition is a topical skin preparation for skin whitening.

Description

Composition stably containing Zedelon

The present invention relates to a composition stably containing zederone, and more particularly to a skin external preparation for whitening that stably contains zederone.

Conventionally, various external preparations for whitening have been provided to improve skin color blackness, spots, freckles and the like. Arbutin, kojic acid, ascorbic acid and their derivatives, glutathione, colloidal sulfur and the like are used as well-known substances as whitening ingredients to be blended as an active ingredient of the whitening agent. In recent years, 4-MSK (4-methoxy Salicylic acid potassium salt), lucinol (registered trademark), magnolignan (registered trademark), ellagic acid, linoleic acid, and the like are used as active ingredients of commercially available whitening external preparations.

The present applicant has clarified that an ingredient having a whitening effect superior to the active ingredients of these conventional whitening agents is zederone contained in gajutsu (Our, Curcuma zedoaria Roscoe (aka purple turmeric)). In addition, a patent application has already been filed for a composition containing zederone purified from gadget as an active ingredient (International Patent Application PCT / JP2009 / 070535).

However, it has been clarified that zederone has poor long-term storage stability and is converted to other substances in the preparation and the whitening effect decreases with time.

The present invention has been made in view of the above-mentioned background art, and an object of the present invention is to provide a composition stably containing zederone.

The inventors of the present invention made extensive efforts under the above background art, and found that the stability of zederone can be enhanced by mixing zederone and a specific component, and the present invention has been completed. That is, the present invention

[1] From the group consisting of isolated zederone and whitening agent, chelating agent, antioxidant, polyphenol, plant extract, preservative, vitamin, UV absorber, 1,2-octanediol and 2-ethylhexyl glyceryl ether A composition comprising one or more selected components;
[2] One or more whitening agents selected from the group consisting of isolated zederone and ascorbyl tetra-2-hexyldecanoate, kojic acid, arbutin and ascovir magnesium phosphate; hinokitiol, tartaric acid, citric acid, edet One or more chelating agents selected from the group consisting of disodium acid, tripolyphosphoric acid and hexametaphosphoric acid; selected from the group consisting of d-δ-tocopherol, ferulic acid, α-lipoic acid, thiotaurine, cysteine and glutathione One or two or more antioxidants; one or more polyphenols selected from the group consisting of gallic acid and resveratrol; a group consisting of sunflower seed extract, locust root extract, saxima button bud extract and rose flower extract Extraction of one or more plants selected from One or more preservatives selected from the group consisting of chlorhexidine gluconate, 2-phenoxyethanol, methyl p-hydroxybenzoate, isopropylmethylphenol, benzoic acid and salicylic acid; pyridoxine hydrochloride, nicotinamide, thiamine hydrochloride And one or more vitamins selected from the group consisting of nicotinic acid; 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine, 2-cyano One or more UV absorbers selected from the group consisting of -3,3-diphenylprop-2-enoic acid 2-ethylhexyl ester, diethylaminohydroxybenzoyl hexyl benzoate and 2-ethylhexyl paramethoxycinnamate, and 1,2-octanediol and 2-ethyl Hexyl glyceryl ether, the composition of [1], further comprising a one or more components selected from the group consisting of;
[3] The composition according to the above [1] or [2], comprising about 0.000001 to 1.0% by mass of isolated zederone;
[4] The composition according to the above [3], comprising about 0.001 to 0.1% by mass of isolated zederone;
[5] The composition according to any one of [1] to [4] above, wherein the isolated zederon is isolated from Curcuma zedoaria;
[6] The composition according to any one of [1] to [5], which is a skin external preparation for whitening;
[7] A composition comprising about 0.05 to 0.2% by mass of isolated zederone, wherein the residual amount of zederone after storage for 2 months at 40 ° C. in the dark is changed to the residual amount after storage for 2 months at 4 ° C. The composition according to any one of [1] to [6], wherein the composition is about 88% or more;
[8] A composition containing about 0.05 to 0.2% by mass of isolated zederone, wherein the residual amount of zederone after storage for 1 month at 60 ° C. under light shielding is the residual amount after storage for 1 month at 4 ° C. The composition according to any one of [1] to [7], wherein the composition is about 89% or more;
[9] A composition containing about 0.05 to 0.2% by mass of isolated zederone, wherein the residual amount of zederone after storage for 2 months at 40 ° C. in the dark is changed to the residual amount after storage for 2 months at 4 ° C. The composition according to any one of [1] to [8], wherein the composition is about 92% or more;
[10] A composition containing about 0.05 to 0.2% by mass of isolated zederone, wherein the residual amount of zederone after storage for 1 month at 60 ° C. under light shielding is the residual amount after storage for 1 month at 4 ° C. The composition according to any one of [1] to [9] above, which is about 93% or more; and [11] a composition comprising about 0.05 to 0.2% by mass of isolated zederone, The remaining amount of zederone after 1 year storage at room temperature is about 88% or more with respect to the remaining amount after 1 year storage at 4 ° C, according to any one of [1] to [10] above A composition is provided.

According to the present invention, zederone that exhibits a high whitening effect can be stably blended into a preparation system over a long period of time. Therefore, according to this invention, the skin external preparation for whitening which exhibits the extremely high whitening effect stably can be provided.

It is a flowchart which shows the fraction by a liquid-liquid distribution from a gajutsu extract powder (A). It is the photograph which shows the melanin production inhibitory effect by the liquid-partition distribution of gorgeous extract powder (A), (a) is a control, (b) is arbutin, (c) is gudget extract powder (A), (d) is The hexane fractions (B) and (e) are the results of the ethyl acetate fraction (C), and (f) are the results of the water fraction (D). It is a chromatogram by preparative thin layer chromatography. It is a chromatogram of each fraction obtained by preparative thin layer chromatography. It is a photograph which shows the melanin production inhibitory effect of the fraction obtained by preparative thin layer chromatography, (a) is a control, (b) is arbutin, (c) is a gadget extract powder (A), (d) Is the hexane fraction (B), (e) is sample B-1 (band S1), (f) is sample B-2 (band S2), (g) is sample B-3 (bands S3 to S5), ( h) is the result of sample B-4 (bands S6 to S8). It is an ultraviolet absorption spectrum of a purified melanin production inhibitor (Zedron). It is the chart by IR of the refined melanin production inhibitory substance (Zederon). 2 is a mass spectrum of a purified melanin production inhibitor (Zederon). ^{1 is} a ¹ H-NMR spectrum of a purified melanin production inhibitor (Zederon). 3 is a ¹³ C-NMR spectrum of a purified melanin production inhibitor (Zederon). 3 is an HPLC chart of a fraction eluted with hexane-ethyl acetate (8: 2) of ganjyu extract powder (A). It is a photograph which shows the melanin production inhibitory effect by the product of manufacture example 1, Comprising: (a) is a control, (b) is arbutin, (c) is a gadget extract powder (A), (d) is a result of manufacture example 1. It is.

In the first aspect, the present invention relates to an isolated zederone, a whitening agent, a chelating agent, an antioxidant, a polyphenol, a plant extract, an antiseptic, a vitamin, an ultraviolet absorber, 1,2-octanediol and 2- Provided is a composition comprising one or more components selected from the group consisting of ethylhexyl glyceryl ether.
Zedelone used as an active ingredient in the composition of the present invention has the formula (1):

It is represented by

This Zedelon is extracted from various parts of the roots, stems, leaves, etc. of the gadget (Curcuma zedoaria Roscoe (aka purple turmeric) or whole plant, preferably from the roots with various organic solvents, and activated carbon, styrene-divinylbenzene. It can be obtained by purification using a synthetic synthetic adsorbent (for example, Mitsubishi Kasei Co., Ltd .: HP-20), octadecylsilylated silica gel or silica gel. At this time, as an extraction solvent, water, methanol, lower alcohol having about 1 to 4 carbon atoms such as ethanol or an aqueous solution thereof, ketones such as acetone and methyl ethyl ketone, esters such as methyl acetate, ethyl acetate, butyl acetate, One or two or more solvents selected from various types of saturated and unsaturated hydrocarbons, whether linear or branched, such as n-pentane, n-hexane, cyclohexane, benzene or toluene can be used. These solvents are properly used, for example, polar solvents are preferably used rather than nonpolar solvents for extraction from plants, and then fractionation can be performed by lowering the polarity.

More specifically, the zederone used in the composition of the present invention is:
(1) Prepare a garnet extract by immersing the dried cucumber (Curcuma zedoaria) in a solvent.
(2) Distilling off the solvent of the ganj extract under reduced pressure,
(3) The produced crystal content can be washed with a small amount of solvent, and then (4) the obtained crystal content can be obtained by a recrystallization process from the solvent.

Moreover, the zederone used for the composition of the present invention is:
(1) A dried extract of gadget is soaked in a solvent to prepare a gadget extract,
(2) Distilling off the solvent of the ganj extract under reduced pressure,
(3) Dissolving the dried product thus obtained in a solvent and performing fractionation by column chromatography using silica gel as a filler, and then (4) crystallizing the solvent distillate of the fraction from the solvent. It can obtain by the manufacturing method containing.

In a preferred form, the preparation of the jar juice extract is about 1:50 to about 1: 3 (volume ratio), preferably about 1:10 to about 1: 4 (volume ratio) of jar juice dry matter: solvent bath ratio. From about 10 ° C. to the boiling point of the extraction solvent, preferably from room temperature to about 10 ° C. lower than the boiling point of the solvent, for about 2 hours to about 14 days, preferably about 7 days, with stirring, Soxhlet extraction or standing. .

In a preferred embodiment, the solvent used for operations such as extraction, adsorption, liquid partitioning, crystallization, and chromatography mobile phase is water, methanol, ethanol, 30-95% (v / v) methanol aqueous solution or ethanol aqueous solution, It is hexane or ethyl acetate, and these solvents can be used alone or in combination.

In a preferred form, the chromatography conditions are as follows.
Column: Chemcobond 5-ODS-W (6.0 x 150 (6A)) (Chemco Corporation)
Mobile phase: 75% (v / v) aqueous methanol column temperature: 55 ° C
Flow rate: 1.0mL / min
Injection volume: 10μL
Monitor: UV 280nm Absorbance

In a preferred form, the zederone contained in the composition of the present invention is
(1) Soaked dried radish rhizomes in ethyl acetate and allowed to stand at room temperature for extraction.
(2) The extract was filtered through a filter (ADVANTEC No.131), the solvent was distilled off under reduced pressure,
(3) The dried product was subjected to column chromatography (same as the above analysis conditions) with silica gel as a packing material using a mixed liquid of hexane and ethyl acetate (volume ratio 7: 3) as the mobile phase, and the wavelength was 210 nm. Perform fractionation using ultraviolet absorption as an index,
(4) Collect the fraction in which absorption was observed, distill off the solvent under reduced pressure, and (5) obtain by a production method including the step of recrystallizing the distillate with hexane to obtain zederone. Can do.

However, the zederone used in the composition of the present invention does not need to be purified to a single pure component, and as described in the following examples, extraction, adsorption, liquid partitioning, and crystallization using various solvents. , Relatively high concentration by operation such as chromatographic fractionation, for example, 60% (w / w) or more, 65% or more, 70% or more, 75% or more, preferably 80% or more, more preferably 85% or more And more preferably 90% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, most preferably 99.5% or more as a crude product containing components with a purity of 99.5% or more. Is also possible.

In addition to the zederone obtained by the method described in this specification, a commercially available product can be used.

Zederone contained as an active ingredient in the composition of the present invention is approximately 400 times more effective than arbutin, which is said to have a high melanin production inhibitory effect, that is, equivalent to about 1/400 of the amount of arbutin used. Shows an inhibitory action on melanin production (International Patent Application PCT / JP2009 / 070535).

In the compositions of the present invention, zederone is about 0.000001 to 1.0% by weight, preferably about 0.0001 to 0.5% by weight, and most preferably about 0.0001 to 0.00% by weight of the total composition. 1 mass% can be included. When the amount of zederone in the composition is less than about 0.000001% by mass, an effective whitening effect cannot be exhibited. On the other hand, if the amount exceeds 1.0% by mass, a further effect can be obtained. Can not.
Based on the result of HPLC analysis (not shown) of the 70% (v / v) aqueous ethanol extract, which had the highest extraction efficiency of zederone from gadget, about 0.3% of the dried product was present in gadget. % Zederone. The extract of gadgets that can be used as a cosmetic raw material is a water extract, an ethanol extract, or an extract of a water / ethanol mixture. In these extracts, from 1 kg of the dried raw plant material, at least about 25 g of the extracted dried product (gadget dry extract) is obtained. Then, only about 10% by mass of zederone is contained in the gadget extract (converted into a dry product) blended in the cosmetic. Considering the odor and coloring, the blending amount of the ganj extract is approximately 0.01% by mass in the cosmetics, and at most about 0.05% by mass or less in terms of dry matter. Therefore, the zederone content in the cosmetics known so far is about 0.005% by mass at most. Therefore, in the skin whitening preparation for whitening of the present invention, it is preferable to add about 0.005% by mass or more of zederone, more preferably about 0.01% by mass or more of zederone. Thereby, the whitening effect which the conventional whitening cosmetics do not have can be exhibited.

In the composition of the present invention, the components that maintain the stability of zederone include whitening agents, chelating agents, antioxidants, polyphenols, plant extracts, preservatives, vitamins, UV absorbers, 1,2- Octanediol and 2-ethylhexyl glyceryl ether are included.
Preferred whitening agents include ascovir tetra-2-hexyldecanoate, kojic acid, arbutin and ascovir magnesium phosphate, more preferably kojic acid and arbutin, most preferably kojic acid.
Preferred chelating agents include hinokitiol, tartaric acid, citric acid, disodium edetate, tripolyphosphoric acid and hexametaphosphoric acid, more preferably hinokitiol, citric acid, tripolyphosphoric acid and disodium edetate, most preferably hinokitiol. is there.
Preferred antioxidants include d-δ-tocopherol, ferulic acid, α-lipoic acid, thiotaurine, cysteine and glutathione, more preferably ferulic acid, α-lipoic acid and thiotaurine, most preferably thiotaurine. is there.
Preferred polyphenols include gallic acid and resveratrol, more preferably gallic acid.
Preferred plant extracts include sunflower seed extract, itadori root extract, saxima button bud extract and rose flower extract, more preferably sunflower seed extract, itadori root extract and rose flower extract, most preferably is there.
Preferred preservatives include chlorhexidine gluconate, 2-phenoxyethanol, methyl p-hydroxybenzoate, isopropylmethylphenol, benzoic acid and salicylic acid, more preferably 2-phenoxyethanol, methyl p-hydroxybenzoate and isopropylmethylphenol. Most preferred is 2-phenoxyethanol.
Preferred vitamins include pyridoxine hydrochloride, nicotinamide, thiamine hydrochloride and nicotinic acid, more preferably pyridoxine hydrochloride and nicotinic acid, most preferably pyridoxine hydrochloride.
Preferred UV absorbers include 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine, 2-cyano-3,3-diphenylprop-2-enoic acid 2-ethylhexyl ester, diethylaminohydroxybenzoyl hexyl benzoate and 2-ethylhexyl paramethoxycinnamate, more preferably 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3 2,5-triazine and 2-ethylhexyl paramethoxycinnamate, most preferably 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine.

In the composition of the present invention, these components maintaining the stability alone or in combination are about 0.005 to 10.0% by weight, preferably about 0.01 to 5.0% by weight, based on the whole composition. Most preferably, it can be contained in an amount of about 0.05 to 1.0% by mass. If the amount of these components in the composition is less than about 0.005% by mass, the stability of zederone cannot be maintained, while if the amount exceeds 10.0% by mass, a further maintenance effect is obtained. Can't get.

Further, in the composition of the present invention, in addition to the above-mentioned components for maintaining the stability of zederone and zederone, a solvent can be used as desired as a component for assisting the dissolution of both components. Solvents that can be used are not limited as long as they are used in cosmetics and external medicines, and can dissolve the above-mentioned zederone and the above-mentioned components. For example, water, ethanol, Polar solvents such as 1,3-butylene glycol, propylene glycol (1,2-propanediol), 1,3-propanediol, dipropylene glycol, ethoxydiglycol, methoxyethanol, and mixtures thereof, preferably water Ethanol, aqueous ethanol solution, 1,3-butylene glycol, and 1,3-butylene glycol aqueous solution, most preferably aqueous ethanol solution. These solvents may be contained alone or in combination in an amount of about 0 to 99.9% by weight, preferably about 0 to 70.0% by weight, and most preferably about 0 to 50.0% by weight based on the total composition. .

The composition of the present invention can be prepared by dissolving either zederone or a component that maintains stability in a solvent and then dissolving the other component in the solution.

In the second aspect, the present invention provides a skin whitening preparation for whitening comprising a composition comprising the above-mentioned zederone and a component for maintaining the stability thereof.
The external preparation for skin of the present invention is usually used by blending the above-described composition of the present invention with various cosmetic bases or external pharmaceutical bases, such as creams, emulsions, lotions, packs, Various basic cosmetics such as facial cleansers, various makeup cosmetics such as foundations, cheeks and white powders, various cosmetics for hair such as hair shampoos, hair nourishing agents, shampoos and rinses, and other cosmetics such as soaps, beauty nails and cologne In addition, it is provided as an external preparation for skin including quasi-drugs and medical external preparations applied to the skin.

Examples of the cosmetic base and the external pharmaceutical base include various oily raw materials such as oils and waxes, hydrocarbon oils, higher fatty acids, ester oils, silicone oils, water, Alcohol and polyhydric alcohol are included. In addition to the above-mentioned bases, the cosmetics and medical external preparations include anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, pH adjusters, various water-soluble high-performance agents. Molecule, thickener, UV absorber, sequestering agent (chelating agent), sugar, amino acid, organic amine, polymer emulsion, vitamins, antioxidant, antioxidant assistant, moisturizer, anti-inflammatory agent, antibacterial Additives other than the components essential to the composition of the present invention, such as agents, cell activators, fragrances, colorants such as pigments and dyes, and preservatives can be blended.

The external preparation for skin of the present invention is not particularly limited in dosage form as a cosmetic or medical external preparation, and examples thereof include liquid forms, emulsions, ointments, sols, gels, powders, sprays and the like. The By using it as such a cosmetic or a medical external preparation, a whitening effect can be exhibited.

The skin external preparation of the present invention is blended with an effective amount of zederone that exhibits a whitening effect, a component that maintains its stability, and a solvent according to each dosage form.

The amount of zederone in the external preparation for skin of the present invention is about 0.000001 to 1.0% by mass, preferably about 0.0001 to 0.5% by mass, and most preferably about 0.0001 to 0.1% by mass. When the amount of zederone in the external preparation for skin is less than about 0.000001% by mass, an effective whitening effect cannot be exhibited. On the other hand, even if it exceeds about 1.0% by mass, a further effect is obtained. Can't get.

The amount of the component for maintaining the stability of zederone in the external preparation for skin of the present invention is about 0.005 to 10.0% by mass, preferably about 0.01, alone or in combination with respect to the entire external preparation for skin. To 5.0% by weight, most preferably about 0.05 to 1.0% by weight. If the amount of these components in the external preparation for skin is less than about 0.005% by mass, the stability of zederone cannot be maintained, while if the amount exceeds about 10.0% by mass, it will not exceed that. A maintenance effect cannot be obtained.

Further, the amount of the solvent that can be optionally used in the external preparation for skin of the present invention is about 0 to 99.9% by mass, preferably about 0 to 50.0% by mass, alone or in combination with respect to the total external preparation for skin. %, Most preferably about 0 to 20.0% by weight.

The skin external preparation of the present invention is a skin external preparation in which zederone isolated from a natural product or synthesized zederone is stably blended for a long period of time in the above-mentioned base, Contains no natural product extract. That is, this external preparation for skin obtained by blending isolated zederone as an active ingredient without using a natural product extract containing zederone is preferably used as a whitening agent. However, the present invention is characterized by the use of isolated or synthesized zederone as a melanin production inhibitor, and is a natural product extract containing a skin external preparation or zederone artificially added with zederone alone. In addition to products, it has a technical feature in that it exhibits a whitening effect by using a topical skin preparation artificially blended with isolated or synthesized zederone.

Next, the present invention will be described in more detail based on the following examples, but the present invention is not limited to the contents of these examples.

[Extraction and fraction purification from gadgets]
In extracting and purifying the melanin production inhibitor according to the present invention from gadgets, first, fractionation operation was performed by the method shown in FIG. 1, and the whitening effect was examined for each fraction. The whitening action was performed by examining the melanin production inhibitory action as shown below. The gadgets obtained from Shinwa Bussan Co., Ltd. were used.

1800 mL of 50% (v / v) aqueous ethanol solution was added to the dried rhizome of 300 g of gadget (Curcuma zedoaria Roscoe (Zingiberaceae)) and left at room temperature for 5 days. Then, it filtered and 1600 mL extract was obtained. The extract was concentrated under reduced pressure to obtain 7.5 g of a dried product (Gadju extract powder (A)). 1 g of the dried product was dissolved in a small amount of 50% (v / v) ethanol aqueous solution and then poured into a separatory funnel. Further, water and hexane (1: 1 by volume) were added and shaken well. Put. The lower aqueous layer was taken out, and the upper hexane layer was separated into another flask. The taken out aqueous layer was returned to the separatory funnel again, almost the same volume of hexane as the aqueous layer was added, and the same operation was repeated twice more. Next, the aqueous layer was returned again to the separatory funnel, and a liquid separation operation was performed by adding approximately the same volume of ethyl acetate as the aqueous layer. The upper ethyl acetate layer was collected, the taken-out aqueous layer was returned to the separatory funnel, ethyl acetate having the same volume as the aqueous layer was added again, and the same operation was repeated twice more. The collected hexane layer, ethyl acetate layer, and the remaining aqueous layer were concentrated under reduced pressure and used as samples for the melanin production inhibition test (samples (A) to (D)).

(Melanin production inhibition test)
As a melanin production inhibition test, a test using a three-dimensional cultured skin model and a test using the amount of melanin and protein produced at that time as indices were performed.
The melanin production inhibition test was performed using a commercially available three-dimensional cultured skin model (MEL-300 kit Asian donor: Kurabo Industries). Set the MEL-300 skin model cup in each well of a 6-well plate according to the method of using the kit, and warm it in a 37 ° C incubator (EPI-100: SCF at a final concentration of 10 ng / mL when the medium is added) Aseptically, 5 mL each was put into a skin model cup. 100 μL of each sample solution was added directly into the skin model cup, and the 6-well plate containing the skin model cup was placed in an incubator (37 ° C., 5% CO ₂ , humidified state) and cultured for 14 days. Every two days, the medium was replaced with a new medium, and each time 100 μL of the solution of each sample was added to the skin model cup. In addition, PBS (-) for cell culture was used for the preparation of each sample solution.

After culturing, the MEL-300 skin model cup was washed 3 times with PBS (-), the cell part was detached and placed in a 1.5 mL Eppendorf tube, 0.5 mL of 2 mol / L-NaOH was added, and at room temperature. Left overnight. After boiling for 15 minutes, 250 μL of each sample was transferred to a 96-well plate, and melanin was quantified at 405 nm.

Furthermore, 40 μL of the sample for quantifying melanin after boiling was transferred to a 96-well plate, and 200 μL of BCA reagent (trade name: Takara Bio Inc.) for protein quantification was placed in each well and incubated at 37 ° C. for 30 minutes. Thereafter, the absorbance at 540 nm was measured.

The same test was performed using PBS (-) as a control and arbutin-PBS (-) solution (2.0% (w / v)) as a positive control. Relative ratio) and protein amount (relative ratio) were calculated, and the degree of inhibition of melanin production was examined. The results are shown in Table 1. Moreover, the photograph which shows the result of the three-dimensional cultured skin model at that time is shown in FIG.

(Fractionation purification by TLC)
From the results of Table 1 and FIG. 2, it was found that the hexane extract fraction shown in FIG. 1B showed the strongest melanin production suppression degree (FIG. 2D). Therefore, this fraction was further purified using preparative TLC (preparative thin layer chromatography).

After the solvent was distilled off from the hexane extraction layer, the concentrate was dissolved in a small amount of hexane, and mixed with hexane and ethyl acetate in a preparative thin layer plate (silica gel 60 / F254, Merck, thickness 2 mm). Fractionation was performed using (volume ratio 7: 3) as a developing solvent. Detection was performed visually and with a UV lamp having a wavelength of 254/366 nm. The result is shown in FIG. As shown in FIG. 3, three distinct bands (S1 to S3), two bands (S5, S7) that were slightly observed, and one band (S8) tailed from the origin were observed. Therefore, as shown in the figure, it was fractionated into 8 bands (band S1 to band S8). Each fractionated band was scraped and extracted with ethyl acetate, and then ethyl acetate was distilled off to obtain each fraction component.

Next, the fractionation status of the above fraction components was confirmed by TLC. A small amount of each fraction concentrate was dissolved again in a small amount of hexane, and then developed with the above developing solvent using a thin layer plate (silica gel 60 / F254, thickness 0.2 mm (Merck)). The result is shown in FIG. The lanes in which the hexane solutions of bands S1, S2, S3,... S7, S8 are spotted in order from the left are shown. As a result, a single spot was detected in band S2 (detection by iodine).

(Melanin production inhibition test)
Next, the fractionated sample was subjected to a melanin production inhibition test. At the time of the test, based on the results of the TLC, for the bands S1 and S2, each band was used as a sample (sample B-1 and sample B-2), and for the bands S3 to S5 and for the bands S6 to S8, Were used as samples (Sample B-3 and Sample B-4), respectively. Table 2 shows the results of the degree of inhibition of melanin production determined from the amount of melanin and the amount of protein. In addition, as a reference, tests were also conducted on the gadget extract powder (A) and the hexane layer concentrate (B). As a result, the fraction of sample B-2 from which a single spot was obtained showed the strongest inhibition of melanin production. Moreover, the photograph which shows the result of the three-dimensional cultured skin model at this time is shown in FIG.

[Determination of structure of melanin inhibitor]
As shown in Table 2, the fraction of band S2 showed the strongest inhibition of melanin production, and a single spot could be confirmed in detection by ultraviolet absorption and detection by iodine, so melanin present in this fraction The structure of the production inhibitor was determined. Structure determination is based on analysis by ultraviolet absorption spectrum (solvent: hexane), infrared absorption analysis (IR), mass spectrometry, ¹ H-NMR (solvent: CDCl ₃ ) and ¹³ C-NMR (solvent: CDCl ₃ ). went. The results are as follows, and charts according to each analysis are shown in FIGS. The assignment by NMR is shown in Table 3. From these results, the produced melanin production inhibitor was identified as zederone. As can be seen from Table 2, the degree of inhibition of melanin production of this substance shows almost the same effect at a concentration of about 1/400 of the arbutin concentration as compared with arbutin which has been considered to have a whitening effect so far. The action is about 400 times stronger than arbutin.

Properties: White crystalline solid UV absorption: Maximum absorption wavelength (λmax) 281nm
Mass spectrometry: 246 (m / e)
Infrared absorption spectrum (cm ^-1 ): 1662,1523,1427,1400,1232,1066,1020,929,881,863.

[Confirmation of stability]
A solution obtained by dissolving 100 mg of zederone obtained in the above method in 200 mL of 50% (v / v) aqueous ethanol solution was added at a high temperature (60 ° C.), and 0.5 mol / L-NaOH was added to this solution to give a final concentration of 0.125 mol. / L-NaOH solution and 0.5 mol / L-HCl added to a final concentration of 0.125 mol / L-HCl were stored at room temperature to confirm stability. Moreover, what stored the ethanol solution same as the above at 4 degreeC was used for control. Stability was measured by performing high performance liquid chromatography under the following conditions and determining the residual ratio from the percentage by peak area. In addition, the sample solution preserve | saved alkali and acid was measured after neutralization, respectively.

(Analysis conditions)
Column: Chemcobond 5-ODS-W (6.0 x 150 (6A)) (Chemco Corporation)
Mobile phase: Methanol Column temperature: 55 ° C
Flow rate: 1.0mL / min
Injection volume: 10μL
Monitor: UV 280nm Absorbance

The results are shown in Table 4. It is well known that phenolic compounds such as arbutin and ellagic acid brown in the alkaline region, but no change was observed in zederone. In addition, although a slight decrease was observed in the acidic range, it was found that it is stable even in alkaline and high temperature conditions, and zederone can be blended in a composition under various physical conditions. It became clear that it can be used in.

Next, zederone contained as an active ingredient in the composition of the present invention was prepared according to the following production method.
[Production Example 1] 1 kg of dried rhizomes of Zederon gudget (Curcuma zedoaria) was immersed in 6 L of hexane, and allowed to stand at room temperature for 7 days for extraction. The extract was filtered through a filter (ADVANTEC No. 131), the solvent was distilled off from the filtrate under reduced pressure, and the mixture was left in a cool dark place. The produced crystal was separated and washed with a small amount of hexane. Furthermore, the obtained crystal was recrystallized with hexane to obtain 300 mg of Zedelon (purity of about 95%). The purity was determined by operating under the above liquid chromatography conditions. The zederone obtained in Example 1 was used as a standard product, and zederone was quantified from the peak height ratio at a detection wavelength of 220 nm (the same applies to Production Example 2).

[Production Example 2] 1 kg of dried Zedelon radish was dipped in 6 L of ethyl acetate and allowed to stand at room temperature for 4 days for extraction. The extract was filtered through a filter (ADVANTEC No.131), the solvent was distilled off from the filtrate under reduced pressure, and the mobile layer was then mixed with silica gel using a mixture of hexane and ethyl acetate (volume ratio 7: 3). Purification by column chromatography (same as the above analysis conditions) using as a filler. Fractionation was performed with a fraction collector, and fractionation was performed using ultraviolet absorption at a wavelength of 280 nm measured for each fraction as an index. The solvent distillate of the fraction in which absorption was observed was recrystallized using hexane to obtain 2200 mg of white crystals (zederone content of 2000 mg).

[Inhibition test of melanin production using human melanocytes]
(Human melanocyte culture)
Human melanocytes (NHEM (Moderately), Kurabo Corp.) are seeded at 2.5 × 10 ⁴ per well in a 12-well plate containing 1000 μL of Medium 254 medium (containing growth factor HMGS-2), and the next day stem cells are placed in the medium. Growth factors (SCF, final concentration 10 ng / mL) and test samples were added after 4 hours. It was incubated at 37 ° C., the medium was changed after 3 days, SCF (final concentration 10 ng / mL) was added again, a test sample was added 4 hours later, and incubated at 37 ° C. for 7 days. Thereafter, the amount of melanin and the amount of protein were measured according to the following method.

(Quantification of melanin)
The medium in the well was removed, and the cells were washed 3 times with 500 μL of PBS (−), and then PBS (−) was completely removed. 400 μL of 2 mol / L-NaOH was added to the washed cells to lyse the cells, and the cells were shaken for 30 minutes to prepare a cell lysate. Each cell lysate was transferred to a 1.5 mL Eppendorf tube, heated with boiling water for 10 minutes, and stirred vigorously with a Voltex mixer. 350 μL of this was transferred to a 96-well, and the absorbance was measured at 405 nm.

(Quantification of protein)
40 μL of the cell lysate obtained above was mixed with 200 μL of BCA solution and incubated at 37 ° C. for 30 minutes, and then the absorbance was measured at 540 nm.

For the zederone obtained in [Production Example 1], a melanin production inhibition test was performed using the quantification of melanin and protein as an index. Table 5 shows the amount of melanin and protein by each component. The zederone obtained in [Production Example 1] was found to have a melanin production inhibitory effect that was approximately the same as or exceeded that of zederone isolated by thin layer chromatography.

Zederon is less toxic to cells than arbutin, which is known to have a whitening effect, and was confirmed to show a whitening effect at a very low concentration.

Further, in the same manner as described above (melanin production inhibition test), a melanin production inhibition test was performed on the zederone obtained in [Production Example 1] using a three-dimensional skin culture model. The results are shown in Table 6 and FIG. The zederone obtained in [Production Example 1] was found to have almost the same inhibitory effect on melanin production as zederone isolated by thin layer chromatography.

[Sensory evaluation test]
(Selection of subjects)
Six men (20 to 50 years old) with healthy skin were selected.

(Sample preparation)
(I) Arbutin solution (positive control; 7% by mass)
(Ii) Zederon (2 concentrations; 0.01% by mass, 0.0025% by mass)
(Iii) Gadget extract powder (A) (0.05% by mass of dried extract)
(Iv) Active ingredient-not contained Using a total of 5 samples, 8% by mass of 1,3-butylene glycol, 5% by mass of glycerin, 0.3% by mass of polyoxyethylene coconut oil fatty acid sorbitan (20E. O.), 0.2% by mass of paraben and the remaining amount of purified water, a lotion was prepared by a method known per se to obtain a sample preparation.

(UV irradiation to humans)
A UV irradiation site (1.5 x 1.5 cm) is set on the abdominal skin of 6 subjects, and a medium wavelength range ultraviolet ray (Dermalley M-DMR 80, Toshiba Medical Supplies) is 1.5 times the minimum erythema amount. Irradiated. From the day of irradiation, the sample formulation was applied daily for 4 weeks, each morning and night. Four weeks after the ultraviolet irradiation, each part was determined by visual inspection, and the degree of recovery of pigmentation in the application part of the active ingredient-non-containing preparation (control) and the application part of each sample preparation was determined according to the following evaluation criteria.

(Judgment method)
Four weeks after the irradiation date, the photograph was taken and the effect was judged according to the evaluation criteria.
(Evaluation criteria)

(Measurement method)
(1) First, a photograph is taken with the same positional relationship (state) as the previous time. (Looking at the previous data, the first shooting is optional)
(2) The effect was judged by 10 expert judges.

(result)

As shown in Table 8, Zedelon showed a recovery of pigmentation at an extremely low concentration compared to arbutin, which is known to have a whitening effect, and was effective against skin in an actual human tanned state. However, it was confirmed that an excellent whitening effect was exhibited. Further, no skin irritation reaction such as erythema or eczema was observed at the sample application site of the subject, and it was confirmed that zederone is highly safe even in the form of the preparation.

[Stability test]
In Example 1, it was shown that zederone is stable as a single component in a short period of time. However, when long-term stability in a preparation system was examined, it was found that it was converted to other substances over time.
Accordingly, substances that can improve the stability of Zedelon were screened from substances that can be formulated as an external preparation for skin.
(Preparation of sample solution)
0.2 g of the following sample was taken and dissolved in 10 mL of solvent (water or 99.5% (v / v) ethanol). The plant extract was taken in an amount corresponding to 10% by mass and diluted with 10 mL of 50% (v / v) aqueous ethanol solution.
(Study sample)
Whitening agents: Ascorbic acid glucoside (Hayashibara Biochemical Laboratories), Ascorbyl tetra-2-hexyldecanoate, linoleic acid, kojic acid, arbutin and ascorbyl magnesium phosphate Chelating agents: Hinokitiol, tartaric acid, citric acid, disodium edetate, tripolylin Acid and hexametaphosphoric acid Antioxidants: d-δ-tocopherol, ferulic acid, α-lipoic acid, thiotaurine, cysteine and glutathione Polyphenols: gallic acid and resveratrol And rose flower extract Preservatives: Chlorhexidine gluconate, 2-phenoxyethanol (Toho Chemical Industries), methyl p-hydroxybenzoate (Ueno Pharmaceutical Co., Ltd.), isopropylmethylphenol, benzoic acid and salic Luric acid Vitamin: Pyridoxine hydrochloride, ascorbic acid, nicotinic acid amide, thiamine hydrochloride and nicotinic acid UV inhibitor: 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5 -Triazine (Uvinul T150, BASF Japan), 2-cyano-3,3-diphenylprop-2-enoic acid 2-ethylhexyl ester (Uvinul N539T, BASF Japan), Diethylaminohydroxybenzoyl hexyl benzoate (Uvinul A Plus Gramula, BASF) Japan) and 2-ethylhexyl paramethoxycinnamate (NOMCOAT TAB, Nisshin Oillio Group)
Moisturizer: 1,3-butylene glycol, glycerin, lactic acid, glycolic acid, trehalose, maltitol Other: 1,2-octanediol, 2-ethylhexyl glyceryl ether, phosphoric acid, platinum colloid

The plant extract was obtained by the following method.
Sunflower seed extract 100 g of dried sunflower (Helianthus annuus L (Helianthus)) seeds were pulverized, added with 1000 g of 50% 1,3-butylene glycol, and extracted at 90 ° C. for 1 hour. The extract was cooled and then filtered (ADVANTEC No. 131) to obtain 800 g of a filtrate (sunflower seed extract).

Japanese Knotweed Root Extract To 100 g of dried Knotweed (Polygonium cuspidatum Sieb.et Zucc. (Polygonaceae)) rhizome was added 1000 mL of 50% ethanol, and extraction was performed at room temperature for 4 days. The extract was filtered (ADVANTEC No. 131) to obtain 850 mL of a filtrate (Itadori root extract).

Saxima buttonzul extract 500 mL of water was added to 100 g of dried Saxima buttonzul (Clematis chinensis (Ranunculaceae)) rhizome and extracted at 60 ° C. for 3 hours. The extract was cooled and then filtered (ADVANTEC No. 131) to obtain 400 g of a filtrate. After adding 800 g of 1,3-butylene glycol and allowing to stand at 4 ° C. for 4 days, the mixture was filtered (membrane filter 0.45 μm (ADVANTEC) to obtain 750 g of saximar buttonzul extract.

Rose flower extract To 100 g of dried rose (Rosa centifolia Linne (Rosaceae)) petal, 1000 mL of water was added and extracted at 60 ° C. for 3 hours. The extract was cooled and then filtered (ADVANTEC No. 131) to obtain 800 g of filtrate. After adding 800 g of 1,3-butylene glycol and leaving it to stand at 4 ° C. for 4 days, it was filtered (membrane filter 0.45 μm (ADVANTEC)) to obtain 1550 g of rose extract.

(Long-term stability test)
A 50% (v / v) aqueous ethanol solution containing 0.005% by mass of zederone was prepared, and 0.5 mL of the sample solution was added to 4.5 mL thereof. The sample other than the plant extract was added so that the final concentration was 0.2% by mass or 0.05% by mass, and the sample of the plant extract was added so that the final concentration was 1% by mass or 0.25% by mass.
A control solution to which the same amount of 50% (v / v) ethanol aqueous solution was added instead of the prepared sample solution was stored at 40 ° C. for 2 months or 60 ° C. for 1 month in the dark. After storage for 1 or 2 months, take 50 μL of the sample solution, add 50 μL of internal standard (0.1 mg / mL triclosan ethanol solution), add 900 μL of 70% (v / v) aqueous methanol solution, and filter through a membrane filter. The amount of zederone was analyzed using liquid chromatography under the following conditions with the sample solution. The results are shown in Table 9 as relative ratios to the amount of zederone after being stored at 4 ° C. for the same period under light shielding.

Liquid chromatography conditions Column: Chemcobond 5-ODS-W (6.0 x 150 (6A)) (Chemco Corporation)
Mobile phase: methanol: water = 75:25
Column temperature: 55 ° C
Flow rate: 1.0mL / min
Detection: UV 280nm Absorbance Injection volume: 10μL

In the control group to which the 50% (v / v) aqueous ethanol solution was added, the zederone relative ratio decreased to 83.3% after 2 months at 40 ° C. It can be said that the stability was improved by about 25%, and samples showing 92% or more improved the stability of zederone by about 50%.
In addition, since the relative zederone ratio decreased to 85.1% in the control group after 60 ° C. and 1 month later, the samples having a zederone relative ratio of 89% or more improved the stability of zederone by about 25%. It can be said that samples showing about 93% or more improved the stability of zederone by 50%.

The component that improves the stability of zederone used in the composition of the present invention or the external preparation for skin is preferably about 88% or more after storage at 40 ° C. for 2 months or about 89% or more after storage at 60 ° C. for 1 month. The ratio is more preferably about 92% or more after storage at 40 ° C. for 2 months or about 93% or more after storage at 60 ° C. for 1 month.

Therefore, among the tested ingredients, long-term zederone for whitening agents, chelating agents, antioxidants, polyphenols, plant extracts, preservatives, vitamins, UV absorbers, 1,2-octanediol and 2-ethylhexyl glyceryl ether. It became clear that stability was improved. In particular, ascorbyl tetra-2-hexyldecanoate, kojic acid, arbutin and ascovir magnesium phosphate; hinokitiol, tartaric acid, citric acid, edetate disodium, tripolyphosphate and hexametaphosphate; d-δ-tocopherol, ferulic acid, α-lipo Acid, thiotaurine, cysteine and glutathione; gallic acid and resveratrol; sunflower seed extract, locust root extract, saxima bottal extract and rose flower extract; chlorhexidine gluconate, 2-phenoxyethanol, methyl p-hydroxybenzoate, isopropylmethylphenol, Benzoic acid and salicylic acid; pyridoxine hydrochloride, nicotinic acid amide, thiamine hydrochloride and nicotinic acid; 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1, , 5-triazine, 2-cyano-3,3-diphenylprop-2-enoic acid 2-ethylhexyl ester, hexyl diethylaminohydroxybenzoylbenzoate and 2-ethylhexyl paramethoxycinnamate, and 1,2-octanediol and It has been found that 2-ethylhexyl glyceryl ether increases the long-term stability of zederone.

Furthermore, the effect of combining a plurality of components that showed the effect of increasing the stability in the above test into a preparation system was examined. The results are shown in Table 10.

As is clear from Table 10, these components were shown to enhance the long-term stability of zederone even when they were combined in combination in the formulation system.

The following is a formulation example of a skin external preparation that stably contains the zederone of the present invention.

<Prescription example> Lotion (mass%)
Zederon 0.001
Glycerin 5.0
Polyoxyethylene sorbitan monolaurate (20E.0.) 1.5
Ethanol 8.0
Triethyl citrate 2.0
Methyl p-hydroxybenzoate 0.10
Edetic acid Na 0.05
Purified water balance total 100.0

<Prescription example> Lotion (mass%)
Zederon 0.020
Glycerin 2.0
1,3-butylene glycol 7.0
Polyoxyethylene sorbitan monolaurate (20E.0.) 1.5
2-Ethylhexyl glyceryl ether 0.05
Hexametalin Sun Na 0.05
Preservative / Antioxidant Appropriate amount Purified water balance Total 100.0

<Prescription example> Emulsion (mass%)
Zederon 0.010
Squalane 8.0
Vaseline 2.0
Beeswax 0.5
Sorbitan sesquioleate 0.8
Polyoxyethylene oleyl ether (20E.0.) 1.2
Carboxyvinyl polymer 0.2
Glycerin 1.5
Potassium hydroxide 0.1
Ethanol 7.0
Methyl p-hydroxybenzoate 0.10
Kojic acid 0.50
Purified water balance total 100.0

<Prescription example> Emulsion (mass%)
Zederon 0.005
Squalane 8.0
Vaseline 2.0
Beeswax 0.5
Sorbitan sesquioleate 0.8
Polyoxyethylene oleyl ether (20E.0.) 1.2
Carboxyvinyl polymer 0.2
1,3-butylene glycol 5.0
Potassium hydroxide 0.1
2-Ethylhexyl glyceryl ether 0.05
Rose extract 0.50
Purified water balance total 100.0

<Prescription example> Essence (mass%)
Zederon 0.01
POB (3) POE (8) POP (5) Glyceryl ether 5.0
Squalane 8.0
Vaseline 2.0
Beeswax 0.5
Sorbitan sesquioleate 0.8
Carboxyvinyl polymer 0.2
Glycerin 1.5
Ethanol 7.0
Methyl p-hydroxybenzoate 0.10
Ferulic acid 0.05
Potassium hydroxide appropriate amount Purified water balance Total 100.0

<Prescription example> Essence (mass%)
Zederon 0.01
Glyceryl monostearate 0.7
Sorbitan sesquioleate 1.7
Stearic acid 0.3
Ceramide 0.05
Squalane 3.5
Glycyrrhetinic acid ester 0.05
Cholesteryl hydroxystearate 1.0
Medfoam oil 6.0
Jojoba oil 3.5
Lauroyl glutamate di (octyldodecyl /
Phytostearyl / behenyl) 1.0
Agar 0.25
Sucrose fatty acid ester 0.20
1,3-butylene glycol 6.0
Glycerin 4.5
Trimethylglycine 1.5
Silicone resin 0.05
Hyaluronic acid (0.5% aqueous solution) 0.5
Thiotaurine 0.05
2-Ethylhexyl glyceryl ether 0.05
Saxima Buttonzul Extract 0.50
Purified water balance total 100.0

<Prescription example> Pack agent (mass%)
Zederon 0.005
Vinyl acetate resin emulsion 15.0
Polyvinyl alcohol 10.0
Jojoba oil 3.0
Glycerin 5.0
Titanium oxide 8.0
Kaolin 7.0
Ethanol 5.0
1,2-octanediol 0.05
Knotweed extract 0.20
Purified water balance total 100.0

<Prescription example> Ointment (mass%)
Zederon 0.005
Stearyl alcohol 18.0
Owl 20.0
Glycerin monostearate 0.3
Vaseline 33.0
2-phenoxyethanol 0.20
Hinokitiol 0.02
Purified water balance total 100.0

<Prescription example> Cream foundation (mass%)
Zederon 0.001
Talc 5.0
Sericite 8.0
Titanium oxide 5.0
Color pigment Appropriate amount Polyglyceryl monoisostearate 3.0
Polyoxyethylene hydrogenated castor oil 1.5
Isotridecyl isononanoate 10.0
1,3-butylene glycol 5.0
2-Ethylhexyl glyceryl ether 0.05
2-phenoxyethanol 0.10
Na tripolyphosphate 0.05
Purified water balance total 100.0

<Prescription example> Sunscreen cosmetics (% by mass)
Zederon 0.005
2-Ethoxyl paramethoxycinnamate 4.0
Titanium oxide 10.0
Zinc oxide 10.0
PEG-9 polydimethylsiloxyethyl dimethicone 1.5
Lauryl PEG-9 polydimethylsiloxyethyl dimethicone 1.5
Cyclopentasiloxane 20.0
Dimethicone 10.0
(Dimethicone / Vinyl Dimethicone) Cross Polymer 0.5
Cetyl dimethicone 0.25
Glycyrrhetinic acid ester 0.05
Methyl Gurces-20 1.0
1,3-butylene glycol 10.0
2-Ethylhexyl glyceryl ether 0.05
Edetic acid Na 0.01
Sodium chloride Appropriate amount Purified water balance Total 100.0

This invention relates to the field | area of the composition which is excellent in stability of zederone, and exhibits a very high whitening effect, and a skin external preparation containing the same.

Claims

Selected from the group consisting of isolated zederone and whitening agents, chelating agents, antioxidants, polyphenols, plant extracts, preservatives, vitamins, UV absorbers, 1,2-octanediol and 2-ethylhexyl glyceryl ether A composition comprising one or more components.
One or more whitening agents selected from the group consisting of isolated zederone and ascorbyl tetra-2-hexyldecanoate, kojic acid, arbutin and ascovir magnesium phosphate; hinokitiol, tartaric acid, citric acid, disodium edetate One or more chelating agents selected from the group consisting of tripolyphosphoric acid and hexametaphosphoric acid; one or more chelating agents selected from the group consisting of d-δ-tocopherol, ferulic acid, α-lipoic acid, thiotaurine, cysteine and glutathione Two or more antioxidants; one or more polyphenols selected from the group consisting of gallic acid and resveratrol; selected from the group consisting of sunflower seed extract, locust root extract, saxima button bud extract and rose flower extract One or more plant extracts; One or more preservatives selected from the group consisting of chlorhexidine luconate, 2-phenoxyethanol, methyl p-hydroxybenzoate, isopropylmethylphenol, benzoic acid and salicylic acid; pyridoxine hydrochloride, nicotinamide, thiamine hydrochloride and One or more vitamins selected from the group consisting of nicotinic acid; 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine, 2-cyano- One or more ultraviolet absorbers selected from the group consisting of 3,3-diphenylprop-2-enoic acid 2-ethylhexyl ester, diethylaminohydroxybenzoyl hexyl benzoate and 2-ethylhexyl paramethoxycinnamate, and 1,2-octanediol and 2-ethylhexane Glyceryl ether composition of claim 1 comprising the one or more components selected from the group consisting of.
The composition according to claim 1 or 2, comprising about 0.000001 to 1.0% by weight of isolated zederone.
The composition according to claim 3, comprising about 0.001 to 0.1% by weight of isolated zederone.
The composition according to any one of claims 1 to 4, wherein the isolated zederon is isolated from Curcuma zedoaria.
The composition according to any one of claims 1 to 5, which is a skin external preparation for whitening.
A composition comprising about 0.05 to 0.2% by weight of isolated zederone, wherein the residual amount of zederone after storage for 2 months at 40 ° C. under shading is about the remaining amount after storage for 2 months at 4 ° C. The composition according to any one of claims 1 to 6, which is 88% or more.
A composition comprising about 0.05 to 0.2% by weight of isolated zederone, wherein the residual amount of zederone after storage for 1 month at 60 ° C. under light shielding is about the remaining amount after storage for 1 month at 4 ° C. The composition according to any one of claims 1 to 7, which is 89% or more.
A composition comprising about 0.05 to 0.2% by weight of isolated zederone, wherein the residual amount of zederone after storage for 2 months at 40 ° C. under shading is about the remaining amount after storage for 2 months at 4 ° C. The composition according to any one of claims 1 to 8, which is 92% or more.
A composition comprising about 0.05 to 0.2% by weight of isolated zederone, wherein the residual amount of zederone after storage for 1 month at 60 ° C. under light shielding is about the remaining amount after storage for 1 month at 4 ° C. The composition according to any one of claims 1 to 9, which is 93% or more.
A composition comprising about 0.05 to 0.2% by weight of isolated zederone, wherein the residual amount of zederone after 1 year storage at room temperature is about 4% of the residual amount after 1 year storage at 4 ° C. The composition according to any one of claims 1 to 10, which is 88% or more.