JP2012001467A - Skin external preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin external preparation having a safe and highly active melanogenesis inhibition effect.SOLUTION: The skin external preparation includes a group of compounds having a germacrone-like skeleton as an active ingredient and a specific skin whitening agent, a specific plant or an extract thereof. These compounds can be obtained by purifying a plant such as Curcuma longa L. and Curcuma zedoaria Roscoe. By using the compounds in combination with a specific skin whitening agent, a specific plant or an extract thereof, a remarkable skin whitening effect can be expected in a compounding amount of the skin whitening agent by which the effect could not be obtained in the past.

Description

  The present invention relates to a skin external preparation using a group of compounds having a specific Germaclon-like skeleton and a specific whitening agent, a specific plant or an extract thereof.

  Conventionally, various external preparations for whitening that improve skin color blackness, spots, freckles and the like have been provided. Arbutin, kojic acid, ascorbic acid and derivatives thereof, 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 agents.

  In addition to these compounds, various animal and plant extracts such as rumbling extract, scallop extract, chamomile extract, mulberry white skin extract, placenta extract, and seaweed extract are also used as active ingredients for whitening topical preparations. .

  However, among the components contained in these animal and plant extracts, few have been identified as to which component has a whitening effect. So far, it has only been known that arbutin in a walnut extract has a whitening effect, and in recent years, a condensed tannin-type substance having a specific structure has been whitened from a Jatoba extract, which has a known whitening effect. It is only disclosed that it has an effect | action (refer patent document 1). On the other hand, it is also true that various whitening components have been found from plant extracts whose whitening effect is not known (see, for example, Patent Document 2).

  In addition, ascorbic acid is easily oxidized and unstable, and various derivatives are used. However, as a cosmetic ingredient that touches human skin, a natural product-derived ingredient is preferable. Glutathione and colloidal sulfur have the disadvantage of producing a characteristic odor and precipitation. Animal and plant extracts and seaweed extracts have problems such as insufficient effects and inconsistent quality. Since kojic acid, arbutin and ellagic acid having a phenol group may cause coloring in the presence of an alkali or metal ions, there is a problem in formulation that maintenance of the stability must be considered. In addition, the sesquiterpene lactones described in Patent Document 2 often have a characteristic odor, and it is known that oily compounds are not stable, and it is difficult to stably add them to products. It was. As described above, each of the whitening components so far has certain drawbacks.

On the other hand, the zederone represented by the following chemical formula 1 has been confirmed in the gadgets (Curcuma zedoaria Roscoe (Zingiberaceae): aka purple turmeric) (Non-patent Document 1). Relative plants of the genus Turmeric, such as C. phaeocaulis, turmeric (Curcuma longa [syn. C. domestica]: also known as autumn turmeric), spring turmeric (Curcuma aromatica)
Salisb, Phalaenopsis (Chloranthus serratus)
(Chloranthaceae)) and the like have been reported a lot (see, for example, non-patent documents 2 to 4).

  In addition to the whitening effect, the gadget extract and the turmeric extract have an antiallergic action (see Patent Documents 3 to 6), a slimming action (see Patent Document 7), and a hair growth promoting action (Patent Document) 8), blood circulation promoting action (see Patent Document 9), skin aging and wrinkle-preventing action (see Patent Document 10), and various other pharmacological actions have been reported.

  However, it has been confirmed by the applicant of the present application that autumn turmeric, which is a plant belonging to the turmeric genus, has no whitening effect (see Patent Document 11). However, it was not limited, and it was not considered that Zedron was the essence of the whitening component.

  When referring to zederone as a compound, zederone has antibacterial activity (see Non-Patent Document 5) and has an action of preventing liver damage induced by D-GalN / LPS (see Non-Patent Document 6). It is only known. Further, in Patent Document 3, a gadget extract containing zederone promotes skin activation, and in Patent Document 11, an essential oil component of gadget containing zederone promotes the detoxification function, diuretic action, and cardiotonic action of the liver. It is described that terpenes such as zederone show anti-lifestyle-related disease action (see Patent Document 12), respectively, which show antibacterial action and blood cholesterol inhibitory action (see Patent Document 12). It is not clarified that directly shows these effects.

  In addition, furanodienone contained in gadget is known as a substance having anti-inflammatory activity (see Non-Patent Document 7), and a component isolated from gadget has an action of suppressing stress ulcer and is a substance having anti-ulcer activity. Furanodienone is known (see Non-Patent Document 8).

  Further, furanodienone and cruzelenone are known as substances having antimicrobial action, antibacterial effect, and antiviral effect (see Patent Document 13).

  Thus, so far, there has been no report on the fact that substances such as zederone have a whitening effect, and the fact is that little is known about the whitening component in the extract.

Japanese Patent No. 3650245 Japanese Patent Laid-Open No. 2005-2050 JP-A-2-209804 Japanese Patent Laid-Open No. 61-291524 JP-A-62-108822 JP 09-208480 A Japanese Patent Laid-Open No. 11-193240 Japanese Patent Laid-Open No. 2002-20242 JP 2002-249435 A JP 2005-194246 A JP 2006-246752 A JP 2007-129920 A JP 2000-119188 A

Hiroshi Hikino etal., Chemical Pharmaceutical Bulletin (1968), 16 (6), 1081-1087. Yu-Chi Hou etal., Chinese Pharmaceutical Journal (Taipei) (1997), 49 (2), 119-125. Jun Kawabata et.al., Agricultural and Biological Chemistry (1985), 49 (5), 1479-1485. Minh GiangPhan et al., Tap Chi Hoa Hoc (2000), 38 (4), 96-99. Minh Giang Phan et al., Tap Chi Hoa Hoc (2000), 38 (1), 91-94. Hisashi Matsuda, Chemical Pharmaceutical Bulletin (2001), 49 (12), 1558-1566. H. Makabe et al., Natural Product Research, Part B: BioactiveNatural Products (2006), 20 (7), 680-685. Kazuo Watanabe et al., Yakugaku Zasshi (1986), 106 (12), 1137-1142.

  The present invention has been made in view of the above-mentioned background art, and the object of the present invention is particularly excellent in whitening effect, and when blended in cosmetics, synergistic whitening effect is exhibited, and further safety is achieved. The object is to provide an excellent skin external preparation.

Thus, as a result of intensive studies, the present inventors have found that one or more selected from a group of isolated compounds having a specific Germaclon-like skeleton, a specific whitening agent, a specific plant, or an extract thereof. It has been found that the skin external preparation containing at least one selected from the above exhibits a synergistically excellent whitening effect and is further excellent in safety, and has completed the present invention.
Hereinafter, a group of isolated compounds having a specific Germaclon-like skeleton in the present invention refers to an isolated compound even when simply described as a compound.

The present invention that achieves the above-described object provides at least one selected from one or more selected from a group of isolated compounds having a specific Germaclon-like skeleton, a specific whitening agent, a specific plant, or an extract thereof. For a topical skin preparation containing one or more, a group of isolated compounds having a specific Germaclon-like skeleton,
[1]
formula:
{Where,
R ¹ is H or C _1-3 alkyl;
R ² and R ³ are independently H, OH or C _1-3 alkyl;
Or R ² and R ³ together become = 0,
R ⁴ is H or C _1-3 alkyl;
X and Y are
[Where:
symbol:
Represents a single bond or a double bond;
R ⁵ is H or C _1-3 alkyl;
R ⁶ is H, OH or C _1-3 alkyl;
R ⁷ and R ⁸ are independently H or C _1-3 alkyl, or R ⁵ and either R ⁷ or R ⁸ are not present when bond (1) is a double bond. Or R ⁶ and R ⁷ together form -O-
R ⁹ is H or C _1-3 alkyl;
R ¹⁰ is H or C _1-3 alkyl, or R ¹⁰ is not present when the bond (2) is a double bond].
Or
[Where:
R ¹¹ is linear or branched C _1-5 alkyl or linear or branched C _1-5 alkenyl,
R ¹² is linear or branched C _1-5 alkyl or linear or branched C _1-5 alkenyl;
R ¹³ is H or C _1-3 alkyl] to form a divalent group represented by
One or more isolated compounds represented by:
[2]
The isolated compound is
formula:
{Where,
R ¹ is methyl;
R ² and R ³ are independently H or OH, or R ² and R ³ together are ═O,
R ⁴ is H;
X and Y are
[Where symbol:
Represents a single bond or a double bond;
R ⁵ is H or absent,
R ⁶ is H or OH;
R ⁷ and R ⁸ are independently H or methyl, or when bond (1) is a double bond, R ⁵ and either R ⁷ or R ⁸ are not present, or R ⁶ and R ⁷ together form -O-
R ⁹ is methyl;
R ¹⁰ is H, or R ¹⁰ is not present when the bond (2) is a double bond].
Or
[Where:
R ¹¹ is isopropenyl;
R ¹² is ethenyl;
R ¹³ is methyl] to form a divalent group represented by
One or more isolated compounds represented by:
[3]
The isolated compound is
Zedelon represented by
Furanodienone represented by
Cruzelenone, represented by
Hydrogenated zederon represented by
Or one or more isolated compounds selected from the group consisting of hydrogenated furanodienones.

The specific whitening agent in the present invention includes hydroquinone glycosides and derivatives thereof, kojic acid, ascorbic acid and derivatives thereof, ellagic acid, linoleic acid, salicylic acid and derivatives thereof, placental extract, tranexamic acid and derivatives thereof, resorcin and One or more selected from the derivatives thereof, glycyrrhizic acid and derivatives thereof, and glycyrrhetinic acid and derivatives thereof.

The specific plant or the extract thereof in the present invention is at least one selected from sunflower seed extract, illesen extract, rose extract, itadori extract, licorice extract.

  A group of isolated compounds having a specific Germaclon-like skeleton for use in the present invention is known as a component contained in plants belonging to the family Ginger, including gadgets. In addition, the isolated compound used in the present invention includes those produced by hydrogenating natural components isolated from plants belonging to the family Ginger.

In addition to the above-mentioned substances in the present invention, hydrogenated cruzelenone and the following compounds are known. According to the present invention, one or more compounds selected from these compounds and hydroquinone glycosides are used. Body and derivatives thereof, kojic acid, ascorbic acid and derivatives thereof, ellagic acid, linoleic acid, salicylic acid and derivatives thereof, placenta extract, tranexamic acid and derivatives thereof, resorcin and derivatives thereof, glycyrrhizic acid and derivatives thereof, glycyrrhetinic acid and derivatives thereof The skin external preparation containing at least one selected from the group consisting of derivatives, sunflower seed extract, illessen extract, rose extract, itadori extract, licorice extract also has a synergistically excellent whitening effect. Be expected.

A group of compounds having a specific germacronin-like skeleton of the present invention includes various parts such as roots, stems, leaves, etc. of whole vegetation (Curcuma zedoaria Roscoe (Zingiberaceae), also known as purple turmeric), or various organic compounds, preferably from the roots. It can be obtained by extraction with a solvent and purification using activated carbon, styrene-divinylbenzene synthetic adsorbent (for example, Mitsubishi Kasei Co., Ltd .: HP-20), octadecylsilylated silica gel or silica gel. At this time, as the extraction solvent, water, methanol, a lower alcohol having about 1 to 4 carbon atoms such as ethanol or an aqueous solution thereof, ketones such as acetone or methyl ethyl ketone, esters such as methyl acetate, ethyl acetate, butyl acetate, One type or two or more types of solvents selected from various saturated and unsaturated hydrocarbons such as n-pentane, n-hexane, cyclohexane, benzene, and toluene, regardless of whether they are linear or branched, 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. Further, by hydrogenating the obtained compound according to a known method, a hydrogenated product contained in a group of isolated compounds having a specific Germaclon-like skeleton of the present invention can be obtained.
The compound having a specific germaclon-like skeleton used in the present invention refers to an isolated compound without including a compound contained in a plant extract. However, it is not necessary to purify to a single pure compound, and there is no problem even if it contains some impurities. In other words, the purity is generally within the range recognized as an isolated compound, and as described in the examples below, extraction, adsorption, liquid partitioning, crystallization, chromatography fractionation using various solvents, etc. By the operation, for example, the compound of the present invention can achieve the object of the present invention even with a purity of 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, and most preferably 99.5% or more. Is possible. Of course, a plant extract containing a compound having a specific Germaclon-like skeleton can be added as an additional component.

A group of compounds included as a group of compounds having a specific Germaclon-like skeleton of the present invention include:
Zedelon represented by

Furanodienone represented by

Cruzelenone, represented by

Hydrogenated Zedron represented by

And preferred compounds are zederone, furanodienone and cruzelenone, and most preferred is zederone.
As a group of isolated compounds having these specific Germacron-like skeletons, in addition to the methods described in the present specification, those synthesized by known methods and those commercially available can also be used.

  In the case where an isolated compound having a specific Germacron-like skeleton is used from the gadget extract as used in the present invention, the gadget extract is prepared from about 1:50 to about 1: 3 (volume ratio), preferably About 1:10 to about 1: 4 (volume ratio) of dried gadget: solvent bath ratio of about 10 ° C. to the boiling point of the extraction solvent, preferably about room temperature to about 10 ° C. below the boiling point of the solvent. 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) aqueous methanol solution or aqueous ethanol solution, Hexane or ethyl acetate, and these solvents can be used alone or in combination.

In a preferred embodiment, the zederone contained in the isolated compound having a specific Germacron-like skeleton according to 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 using silica gel as a packing material using a mixed liquid of hexane and ethyl acetate (volume ratio 7: 3) as a mobile phase, and the ultraviolet absorption at 210 nm wavelength was used as an index. Perform
(4) Collect the fraction in which absorption was observed, distill off the solvent under reduced pressure, and (5) obtain the distillate by a production method including the step of recrystallizing with hexane to obtain zederone. be able to.

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 embodiment, the furanodienone contained in the isolated compound having a specific Germaclon-like skeleton according to the present invention is:
(1) Concentrate the dried ganj rhizome by refluxing with hexane,
(2) The dried product obtained by distilling the collected extract under reduced pressure was dissolved in a small amount of hexane,
(3) Apply to a silica column and elute sequentially with hexane, hexane: ethyl acetate (volume ratio 9: 1), hexane: ethyl acetate (volume ratio 8: 2),
(4) Collect the fraction eluted with hexane: ethyl acetate (volume ratio 8: 2), and then (5) dissolve in a small amount of 75% (v / v) aqueous methanol solution and apply to an ODS column. It can be obtained by a production method including a step of fractionating to obtain furanodienone.

In a preferred embodiment, the cruzelenone contained in the isolated compound having a specific Germaclon-like skeleton according to the present invention is:
(1) Concentrate the dried ganj rhizome by refluxing with hexane,
(2) The dried product obtained by distilling the collected extract under reduced pressure was dissolved in a small amount of hexane,
(3) Apply to a silica column and elute sequentially with hexane, hexane: ethyl acetate (volume ratio 9: 1), hexane: ethyl acetate (volume ratio 8: 2),
(4) Collect the fraction eluted with hexane: ethyl acetate (volume ratio 8: 2), and then (5) dissolve in a small amount of 75% (v / v) aqueous methanol solution and apply to an ODS column. It can be obtained by a production method including a step of fractionating to obtain cruzelenone.

In a preferred embodiment, the hydrogenated zederone contained in the isolated compound having a specific Germaclon-like skeleton according to the present invention is:
(1) Dissolve zederone obtained by the above production method in 99.5% (v / v) ethanol,
(2) Add 5% Pd-alumina and perform hydrogenation reaction using hydrogen bag, then (3) Perform filtration after completion of the reaction, and distill off the solvent of the filtrate under reduced pressure to obtain hydrogenated zederone. It can be obtained by a production method including steps.

In a preferred embodiment, the hydrogenated furanodienone contained in the isolated compound having a specific Germaclon-like skeleton according to the present invention is:
(1) Furanodienone obtained by the above production method or the like is dissolved in 99.5% (v / v) ethanol,
(2) Add 5% Pd-alumina and perform hydrogenation reaction using hydrogen bag, then (3) Perform filtration after completion of the reaction, and distill off the solvent of the filtrate under reduced pressure to obtain hydrogenated furanodienone. It can be obtained by a production method including steps.

In a preferred embodiment, the hydrogenated cruzelenone contained in the isolated compound having a specific Germaclon-like skeleton according to the present invention is:
(1) Dissolve kruzelenone obtained by the above-mentioned production method in 99.5% (v / v) ethanol,
(2) Add 5% Pd-alumina and perform hydrogenation reaction using hydrogen bag, then (3) Perform filtration after completion of the reaction, and distill off the solvent of the filtrate under reduced pressure to obtain hydrogenated cruzelenone. It can be obtained by a production method including steps.

  In cosmetics and the like, an effective amount of a group of compounds used in the present invention that exhibits a whitening effect is blended according to each dosage form. Specifically, the blending amount is one or a total of two or more. The amount is about 0.000001 to about 1.0% by mass, preferably about 0.0001 to about 0.01% by mass, and about 0.0001% to about 0.005% based on the total amount of the external preparation for skin. The effect can be obtained with a blending amount of about mass%. In the external preparation for skin of the present invention, it is particularly preferable to add about 0.005% by mass or more of zederone, more preferably about 0.01% by mass or more of zederone.

The specific whitening agent used in combination with a group of compounds having the specific Germacron-like skeleton is not particularly limited as long as it has a melanin production inhibitory action, but in the present invention, the hydroquinone glycoside and its Derivatives, kojic acid, ascorbic acid and its derivatives, ellagic acid, linoleic acid, salicylic acid and its derivatives, placenta extract, tranexamic acid and its derivatives, resorcin and its derivatives, glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, etc. Preferably used.

The hydroquinone glycoside is not particularly limited. For example, hydroquinone-α-D-glucose, hydroquinone-β-D-glucose (arbutin), hydroquinone-α-L-glucose, hydroquinone-β-L-glucose, hydroquinone- Hexacarbon glycosides such as α-D-galactose, hydroquinone-β-D-galactose, hydroquinone-α-L-galactose, hydroquinone-β-L-galactose, hydroquinone-α-D-ribose, hydroquinone-β- D-ribose, hydroquinone-α-L-ribose, hydroquinone-β-L-ribose, hydroquinone-α-D-arabinose, hydroquinone-β-D-arabinose, hydroquinone-α-L-arabinose, hydroquinone-β-L- Five charcoal such as arabinose Glycosides, hydroquinone-α-D-glucosamine, hydroquinone-β-D-glucosamine, hydroquinone-α-L-glucosamine, hydroquinone-β-L-glucosamine, hydroquinone-α-D-galactosamine, hydroquinone-β-D- Amino sugar glycosides such as galactosamine, hydroquinone-α-L-galactosamine, hydroquinone-β-L-galactosamine, hydroquinone-α-D-glucuronic acid, hydroquinone-β-D-glucuronic acid, hydroquinone-α-L-glucuron Uronic acids such as acid, hydroquinone-β-L-glucuronic acid, hydroquinone-α-D-galacturonic acid, hydroquinone-β-D-galacturonic acid, hydroquinone-α-L-galacturonic acid, hydroquinone-β-L-galacturonic acid Examples include glycosides As the derivatives, esters of such acetylated, etc. esters such as methyl iodide and the like. Among these, hydroquinone-β-D-glucose is most preferable from the viewpoints of effects, availability, stability, and the like.

Ascorbic acid and its derivatives are not particularly limited. For example, ascorbic acid monofatty acid esters such as L-ascorbic acid monostearate and L-ascorbic acid monopalmitate, L-ascorbic acid monophosphate and L-ascorbic acid Examples thereof include L-ascorbic acid monoesters such as 2-sulfate ester, L-ascorbic acid glucosides such as L-ascorbic acid 2-glucoside, and salts thereof. Examples of the salt include sodium, potassium, magnesium, ammonium salt, amino acid salt, triethanolamine and the like.

Examples of tranexamic acid and derivatives thereof include tranexamic acid, a dimer of tranexamic acid (for example, trans-4- (trans-aminomethylcyclohexanecarbonyl) aminomethylcyclohexanecarboxylic acid, etc.), an ester of tranexamic acid and hydroquinone ( For example, trans-4-aminomethylcyclohexanecarboxylic acid 4′-hydroxyphenyl ester, etc.), ester form of tranexamic acid and gentisic acid (for example, 2- (trans-4-aminomethylcyclohexylcarbonyloxy) -5-hydroxybenzoic acid) Acid and its salts, etc.), amides of tranexamic acid (for example, trans-4-aminomethylcyclohexanecarboxylic acid methylamide and its salts, trans-4- (P-methoxyvinzoyl) aminomethyl Hexane carboxylic acid and its salts, trans-4-guanidinomethyl cyclohexane carboxylic acid and salts thereof, etc.), and the like.

Examples of salicylic acid and its derivatives include salicylic acid, 3-methoxysalicylic acid and its salt, 4-methoxysalicylic acid and its salt, 5-methoxysalicylic acid and its salt, and the like. Examples of the salt include sodium, potassium, magnesium, triethanolamine and the like.

Examples of resorcin and derivatives thereof include resorcin, alkylresorcinols such as 4-n-butylresorcinol, and salts thereof. Examples of the salt include sodium, potassium, magnesium, triethanolamine and the like.

Examples of glycyrrhizic acid derivatives include, but are not limited to, alkali metal salts such as sodium salts and potassium salts, ammonium salts, basic amino acids, alkanolamine salts, and the like. Specifically, monoammonium glycyrrhizinate, dipotassium glycyrrhizinate, Examples include trisodium glycyrrhizinate and the like. Glycyrrhetinic acid and derivatives thereof are not particularly limited, but include acylated glycyrrhetin, alkyl ether, etc., specifically β-glycyrrhetinic acid, stearyl glycyrrhetinate, glycyrrhetinyl stearate, 3-succinyloxy Examples include disodium glycyrrhetinate.

The specific plant or extract thereof used in combination with the group of compounds having the specific Germacron-like skeleton is not particularly limited as long as it has a melanin production inhibitory action, but in the present invention, sunflower (Helianthus
annus L.) seed extract, Clematischinensis Osbeck extract, rose extract (Rosa
centifolia (Rosaceae)) or hybrid rose (Rosa
Hybrida (Rosaceae))), Knotweed extract (Reynoutria japonica)
Houtt.var.japnica), licorice extract (Glychyrrhiza)
glabra Linne or Glychyrrhiza
uralensis Fisher) and the like are preferably used.

In the present invention, a herbal medicine derived from any part of this plant can be used, but the seed is derived from the sunflower extract, the root extract, the leaf, and the petal derived from the illesen extract, rose extract, itadori extract, and licorice extract. It is preferable to use crude drugs.

The plant extract to be used can be used without any trouble even if it is in the form of an extract obtained by concentrating the extract in addition to the extract itself, or even in the form of powder by freeze drying. In addition, the method for preparing the plant extract is not particularly limited, and various suitable extraction solvents are used for extraction from plants rich in the respective compounds at low temperature and / or under heating. Can be extracted.

The extraction solvent to be used is not particularly limited, and examples thereof include water, lower monohydric alcohols such as methyl alcohol and ethyl alcohol, liquid polyhydric alcohols such as glycerin, propylene glycol, and 1,3-butylene glycol, acetone, and methyl ethyl ketone. One or two or more of ketones such as ethyl acetate, lower alkyl esters such as ethyl acetate, hydrocarbons such as benzene and hexane, ethers such as diethyl ether, and halogenated alkanes such as dichloromethane and chloroform can be used. Of these, water, ethyl alcohol, and a mixed solvent of one or more of 1,3-butylene glycol are particularly suitable.

The plant extract is a raw or dried plant having a weight ratio of 1 to 1000 times, preferably 10 to 100 times, using a solvent at 0 ° C. or higher, preferably 20 ° C. to 40 ° C. for 1 hour or longer. If possible, it is preferably performed for 3 to 7 days. Any part may be used as the extraction site, and whole plant can also be used.

The specific whitening agent or specific plant or extract thereof is preferably added in an amount of 0.0001 to 20% by mass, particularly 0.01 to 10% by mass, in the external preparation for skin of the present invention. If the amount is less than 0.0001% by mass, the effect of the present invention is not sufficiently exhibited. On the other hand, if the amount exceeds 20% by mass, no significant improvement in effect is observed.

  The present invention is usually used by blending with various cosmetic bases and external pharmaceutical bases. For example, various basic cosmetics such as creams, emulsions, lotions, packs, facial cleansers, foundations, cheeks, etc. Various makeup cosmetics such as red and white powder, various hair cosmetics such as hair wash, hair nourishing agent, shampoo, rinse, and other cosmetics such as soap, nail care, eau de cologne, and quasi-drugs and medicines applied to the skin It is provided as an external preparation for skin including external preparations for external use.

  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, alcohols, regardless of whether they are liquid or solid. And polyhydric alcohols. 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 such as agents, cell activators, fragrances, colorants such as pigments and pigments, and preservatives can also be added.

  The dosage form such as cosmetics and medical external preparations is not particularly limited, and examples thereof include liquid forms, emulsions, ointments, sols, gels, powders and sprays. By using it as such a cosmetic or a medical external preparation, a whitening effect can be exhibited.

  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.

[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 gadgets obtained from Shinwa Bussan Co., Ltd. were used.

The structure of this compound 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 result is as follows, and the chart by each analysis is shown in FIGS. Further, assignment by NMR is shown in Table 1. From these results, the produced melanin production inhibitor was identified as zederone.

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.

[Production Example 2] 350 g of dried furanodienone rhizome was refluxed with 1750 mL of hexane for 3 hours. The solvent was filtered off and concentrated. 1750 mL of hexane was added to the residue and refluxed, and the same operation was repeated. The collected extract was distilled off under reduced pressure to obtain 3.12 g of a dried solid product. Dissolve it in a small amount of hexane (about 20 mL), filter the insoluble matter, apply it to a silica column (BW300 (Fuji Silysia), φ = 20 mm, h = 200 mm), hexane, hexane: ethyl acetate (volume ratio) 9: 1) and hexane: ethyl acetate (volume ratio 8: 2) were eluted sequentially with 100 mL each. The fraction eluted with hexane: ethyl acetate (volume ratio 8: 2) was collected, and the solvent was distilled off to obtain a yield of 0.484 g. Next, it was dissolved in a small amount of 75% (v / v) aqueous methanol solution and applied to a column under the following conditions. Fractions were collected using a fraction collector, and each fraction was analyzed using liquid chromatography under the following conditions. Fractions having only a partial peak corresponding to * 1 in the chart of FIG. 6 were collected, and the solvent was distilled off. 0.10 g (yield 0.028%) of a white crystalline solid was obtained. The structure of the melanin production inhibitor existing in this fraction was determined. The structure was determined based on analysis by ultraviolet absorption spectrum (solvent: hexane), infrared absorption analysis (IR), and ¹ H-NMR (solvent: CDCl ₃ ), and the following physical properties were obtained. Charts by ultraviolet absorption and infrared absorption analysis are shown in FIGS.
It was found that the melanin production inhibitor obtained from these physical properties was furanodienone.

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

Ultraviolet absorption: Maximum absorption wavelength (λmax): None Infrared absorption spectrum (cm ⁻¹ ): 1644, 1523, 1375, 1270, 1240, 1105, 1020,931
¹ H-NMR spectrum: 1.30 (3H, s), 1.99 (3H, s), 2.13 (3H, s), 1.85-2.49 (4H, m), 3.70 (2H, m), 5.17 (1H, m), 5.81 (1H, s), 7.07 (1H, s).

[Production Example 3] Cruzelenone Further, fractions having only a partial peak corresponding to * 2 in the chart of FIG. 6 were collected and the solvent was distilled off to obtain 0.07 g (yield 0.02%) of a transparent oily liquid. It was. The structure of the melanin production inhibitor existing in this fraction was determined. The structure was determined based on analysis by ultraviolet absorption spectrum (solvent: hexane), infrared absorption analysis (IR), and ¹ H-NMR (solvent: CDCl ₃ ), and the following physical properties were obtained. The charts by the ultraviolet absorption and infrared absorption analysis are shown in FIGS.
It was found that the melanin production inhibitor obtained from these physical property values was cruzelenone.

Ultraviolet absorption: maximum absorption wavelength (λmax): 272 nm
Infrared absorption spectrum (cm ^-1 ): 1675,1562,1427,1257,1070,997
¹ H-NMR spectrum: 1.222 (3H), 1.658 (3H), 2.97 (1H, q), 2.262 (3H), 3.166 (1H, d), 3.249 (1H, d), 3.104 (1H), 5.028 (1H , d), 5.029 (1H, d), 5.039 (1H, d), 5.126 (1H, d), 5.729 (1H, d), 7.068 (1H).

[Production Example 4] Hydrogenated Zedron 500 mg of Zedelon obtained in Production Example 1 was dissolved in 100 mL of 99.5% (v / v) ethanol, 100 mg of 5% Pd-alumina was added, and hydrogenation reaction was performed using a hydrogen bag. went. The reaction was carried out at room temperature for 15 hours. Filtration was performed after completion of the reaction, and the solvent of the filtrate was distilled off under reduced pressure to obtain 500 mg of a white crystalline solid. The structure of the melanin production inhibitor existing in this fraction was determined. The structure was determined based on analysis by ultraviolet absorption spectrum (solvent: hexane) and ¹ H-NMR (solvent: CDCl ₃ ), and the following physical property values were obtained. A chart obtained by ultraviolet absorption analysis is shown in FIG.
The melanin production inhibitor obtained from these physical properties was found to be hydrogenated zederone.

Ultraviolet absorption: maximum absorption wavelength (λmax): 287 nm
¹ H-NMR spectrum: 2.180 (3H, m), 1.008 (3H, d), 1.059 (3H, d), 7.093 (1H), 1.434 (1H, d), 1.604 (1H, d), 1.434 (1H, d), 1.653 (1H, d), 1.343 (1H, d), 1.474 (1H, d), 2.995 (1H, d), 2.454 (1H, d), 1.743 (1H, d), 1.657 (1H, d ), 2.113 (1H, d), 1.776 (1H, d), 4.199 (1H, d).

[Production Example 5] Hydrogenated Furanodienone 500 mg of furanodienone obtained in Production Example 2 was dissolved in 100 mL of 99.5% ethanol, 100 mg of 5% Pd-alumina was added, and hydrogenation reaction was performed using a hydrogen bag. The reaction was carried out at room temperature for 15 hours. Filtration was performed after completion of the reaction, and the solvent of the filtrate was distilled off under reduced pressure to obtain 500 mg of a white crystalline solid. The structure of the melanin production inhibitor existing in this fraction was determined. The structure was determined based on analysis by ultraviolet absorption spectrum (solvent: hexane) and ¹ H-NMR (solvent: CDCl ₃ ), and the following physical property values were obtained. A chart obtained by ultraviolet absorption analysis is shown in FIG.
The melanin production inhibitor obtained from these physical properties was found to be hydrogenated furanodienone.

Ultraviolet absorption: Maximum absorption wavelength (λmax): None
¹ H-NMR spectrum: 2.167 (3H, m), 0.467 (3H, d), 0.909 (3H, d), 6.594 (1H), 1.440 (1H, d), 1.579 (1H, d), 1.400 (1H, d), 1.779 (1H, d), 1.601 (1H, d), 1.366 (1H, d), 2.808 (1H, d), 2.676 (1H, d), 2.212 (1H, d), 1.884 (1H, d ), 4.774 (1H, d), 3.665 (1H, d).

Sunflower (Helianthusannus L.) seeds, roots of Clematischinensis Osbeck, petals of Western rose (Rosa centifolia (Rosaceae), hybrid rose (Rosa)
Petals of hybrida (Rosaceae), Japanese knotweed (Reynoutria japonica)
Houtt.var.japnica) and 10 g each of various dried plant bodies of licorice (Glychyrrhiza glabra), 100 mL of 50 v / v% ethanol aqueous solution was added, extracted at room temperature for 7 days with occasional stirring and filtered. Each extract was obtained. Each of these extracts was concentrated under reduced pressure and then freeze-dried to obtain an extract.

(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). According to the method of using the kit, a MEL-300 skin model cup is set in each well of a 6-well plate and warmed in a 37 ° C. incubator (EPI-100: SCF reaches 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 preparation of the solution of each sample.

  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.

  A similar 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 Tables 2-9.

From Tables 2 to 16, in Comparative Examples 1 to 32, melanin production was hardly suppressed, whereas in Examples 1 to 120, a compound having a very low concentration of a specific Germaclon-like skeleton and a whitening agent or a specific By combining with a plant extract, an effect of synergistically suppressing melanin production was recognized. Moreover, it was recognized that the suppression rate of the melanin production | generation inhibitory effect becomes high depending on the density | concentration of the compound which has a specific germ macron-like frame | skeleton.

[Sensory evaluation test]
(Selection of subjects)
Eight men (20 to 50 years old) with healthy skin were selected.
〔examined goods〕
It mix | blended with the composition of Table 17 and prepared the composition by the following method.

Using the above sample, 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) was set on the abdominal skin of 8 subjects, and 1.5-fold mid-wavelength UV (Dermalley M-DMR 80, Toshiba Medical Supplies) was the minimum amount of erythema. Irradiated. From the day of irradiation, the sample formulation was applied daily for 4 weeks, each morning and night. After 4 weeks from 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.

(Evaluation criteria)

(Measurement method)
The effect was judged by 10 expert judges.

(result)

  As shown in Table 20, in Comparative Examples 33 and 34, there was not much recovery of pigmentation, whereas in Examples 121 to 136, compared with arbutin known to have a whitening effect. Thus, it was confirmed that the pigmentation was restored by combining extremely low concentrations of zederone, and that it showed an excellent whitening effect even on the skin of an actual human tanned state. Further, no skin irritation reaction such as erythema or eczema was observed at the sample application site of the test subject, and it was confirmed that the preparation was highly safe.

Below, the formulation example which applied the melanin production inhibitor of this invention is given.
<Formulation Example 1> Lotion (mass%)
Zederon 0.005
L-ascorbic acid 2-glucoside 0.5
Polyoxyethylene sorbitan monolaurate (20E.0.) 1.5
1,3-butylene glycol 5.0
Glycerin 3.0
Preservative / Antioxidant Appropriate amount Perfume Appropriate amount Purified water balance Total 100.0

<Formulation example 2> Cosmetic cream (mass%)
Hydrogenated Zedron 0.05
Arbutin 0.5
Beeswax 2.0
Stearyl alcohol 5.0
Stearic acid 8.0
Squalane 10.0
Self-emulsifying glyceryl monostearate 3.0
Polyoxyethylene cetyl ether (20E.0.) 1.0
Propylene glycol 5.0
Potassium hydroxide 0.3
Preservative / Antioxidant Appropriate amount Perfume Appropriate amount Purified water balance Total 100.0

<Formulation example 3> Emulsion (mass%)
Furanodienone 0.01
Kojic acid 0.5
Squalane 8.0
Vaseline 2.0
Beeswax 0.5
Sorbitan sesquioleate 0.8
Polyoxyethylene oleyl ether (20E.0.) 1.2
Carboxyvinyl polymer 0.2
Propylene glycol 0.5
Potassium hydroxide 0.1
Ethanol 7.0
Preservative / Antioxidant Appropriate amount Perfume Appropriate amount Purified water balance Total 100.0

<Prescription Example 4> Essence (mass%)
Zederon 0.001
Ellagic acid 0.5
Sorbit 4.0
1,3-butylene glycol 5.0
Magnesium ascorbate phosphate 0.5
POE monolaurate sorbitan 0.4
Agar 1.0
Native gellan gum 0.5
Trimethylglycine 1.0
Preservative appropriate amount pH adjuster (adjusted to pH 8.0)
Purified water balance total 100.0

<Formulation Example 5> Lotion (mass%)
Cruzelenone 0.01
L-ascorbyl magnesium phosphate 0.5
Glycerin 5.0
Polyoxyethylene sorbitan monolaurate (20E.0.) 1.5
Ethanol 8.0
Triethyl citrate 2.0
Dipotassium glycyrrhizinate 0.05
Preservative / Antioxidant Appropriate amount Purified water balance 10.0

<Formulation Example 6> Lotion (mass%)
Zederon 0.01
Sunflower seed extract 0.010
Glycerin 2.0
1,3-butylene glycol 7.0
Polyoxyethylene sorbitan monolaurate (20E.0.) 1.5
Preservative / Antioxidant Appropriate amount Purified water balance Total 100.0

<Formulation example 7> Emulsion (mass%)
Hydrogenated furanodienone 0.010
Japanese Knotweed Extract 0.010
Squalane 8.0
Vaseline 2.0
Beeswax 0.5
Stearyl glycyrrhetinate 0.05
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
Perfume Appropriate amount Preservative / Antioxidant Appropriate amount Purified water balance Total 100.0

<Prescription Example 8> Emulsion (mass%)
Zederon 0.005
Western rose extract 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
1,3-butylene glycol 5.0
Potassium hydroxide 0.1
Perfume Appropriate amount Preservative / Antioxidant Appropriate amount Purified water balance Total 100.0

<Prescription Example 9> Essence (mass%)
Furanodienone 0.01
Linoleic acid 0.5
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
Licorice extract 0.01
Preservative appropriate amount Potassium hydroxide appropriate amount Purified water balance Total 10.0

<Prescription Example 10> Essence (mass%)
Zederon 0.01
Tranexamic acid 0.5
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
Antioxidant appropriate amount Preservative appropriate amount Purified water balance Total 10.0

<Prescription Example 11> Packing agent (mass%)
Zederon 0.005
Hydrogenated Zedron 0.005
4-Methoxysalicylic acid 0.5
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
Perfume Appropriate amount Preservative / Antioxidant Appropriate amount Purified water balance Total 100.0

<Prescription Example 12> Ointment (mass%)
Zederon 0.005
Furanodienone 0.005
Resorcin 0.5
Octyl paradimethylaminobenzoate 4.0
Butylmethoxybenzoylmethane 4.0
Stearyl alcohol 18.0
Owl 20.0
Glycerin monostearate 0.3
Vaseline 33.0
Perfume Appropriate amount Preservative / Antioxidant Appropriate amount Purified water balance Total 100.0

<Prescription Example 13> Cream Foundation (mass%)
Zederon 0.001
Ireisen extract 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
Antioxidant appropriate amount Preservative appropriate amount Purified water balance Total 10.0

<Prescription Example 14> Sunscreen cosmetic (mass%)
Zederon 0.005
3-O-ethylascorbic acid 0.5
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
Sodium chloride Appropriate amount Antioxidant Appropriate amount Preservative Appropriate amount Purified water balance Total 100.0

<Prescription Example 15> Powder Foundation (mass%)
Zedron 0.01
Talc 43.0
Kaolin 18.0
Mica 8.0
Zinc oxide 10.0
Titanium oxide 5.0
Coloring pigment Appropriate amount Magnesium stearate 6.0
Liquid paraffin 4.0
White petrolatum 1.0
Stearyl glycyrrhetinate 0.05
Ceresin 1.0
Isopropyl myristate 1.5
Preservative / Antioxidant Appropriate amount Perfume Appropriate amount

  The present invention relates to the field of an external preparation for skin having excellent stability and exhibiting an extremely high whitening effect.

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). It is a ¹³ C-NMR spectrum of a purified melanin production inhibitory substance (Zedelon). It is an HPLC chart of a fraction eluted with hexane-ethyl acetate (8: 2) of ganjyu extract powder (A). It is an ultraviolet absorption spectrum of a purified melanin production inhibitor (furanodienone). It is the chart by IR of the refined melanin production inhibitory substance (furanodienone). It is an ultraviolet absorption spectrum of the purified melanin production inhibitory substance (cruzelenone). It is the chart by IR of the refined melanin production inhibitory substance (Cruzelenone). It is an ultraviolet absorption spectrum of the produced | generated melanin production inhibitory substance (hydrogenated zederone). It is an ultraviolet absorption spectrum of the produced | generated melanin production inhibitory substance (hydrogenated furanodienone).

Claims (4)

formula:
{Where,
R ¹ is H or C _1-3 alkyl;
R ² and R ³ are independently H, OH or C _1-3 alkyl;
Or R ² and R ³ together become = 0,
R ⁴ is H or C _1-3 alkyl;
X and Y are
[Where:
symbol:
Represents a single bond or a double bond;
R ⁵ is H or C _1-3 alkyl;
R ⁶ is H, OH or C _1-3 alkyl;
R ⁷ and R ⁸ are independently H or C _1-3 alkyl, or R ⁵ and either R ⁷ or R ⁸ are not present when bond (1) is a double bond. Or R ⁶ and R ⁷ together form -O-
R ⁹ is H or C _1-3 alkyl;
R ¹⁰ is H or C _1-3 alkyl, or R ¹⁰ is not present when the bond (2) is a double bond].
Or
[Where:
R ¹¹ is linear or branched C _1-5 alkyl or linear or branched C _1-5 alkenyl,
R ¹² is linear or branched C _1-5 alkyl or linear or branched C _1-5 alkenyl;
R ¹³ is H or C _1-3 alkyl] to form a divalent group represented by
1 or 2 or more isolated compounds represented by the following, hydroquinone glycosides and derivatives thereof, kojic acid, ascorbic acid and derivatives thereof, ellagic acid, linoleic acid, salicylic acid and derivatives thereof, placental extract, tranexamic acid And derivatives thereof, at least selected from the group consisting of resorcin and derivatives thereof, glycyrrhizic acid and derivatives thereof, glycyrrhetinic acid and derivatives thereof, sunflower seed extract, illesen extract, rose extract, itadori extract, licorice extract A skin external preparation containing one or more kinds. The isolated compound is
formula:
{Where,
R ¹ is methyl;
R ² and R ³ are independently H or OH, or R ² and R ³ together are ═O,
R ⁴ is H;
X and Y are
[Where symbol:
Represents a single bond or a double bond;
R ⁵ is H or absent,
R ⁶ is H or OH;
R ⁷ and R ⁸ are independently H or methyl, or when bond (1) is a double bond, R ⁵ and either R ⁷ or R ⁸ are not present, or R ⁶ and R ⁷ together form -O-
R ⁹ is methyl;
R ¹⁰ is H, or R ¹⁰ is not present when the bond (2) is a double bond].
Or
[Where:
R ¹¹ is isopropenyl;
R ¹² is ethenyl;
R ¹³ is methyl] to form a divalent group represented by
The skin external preparation of Claim 1 which is 1 type, or 2 or more types of isolated compounds represented by these. The isolated compound is
Zedelon represented by
Furanodienone represented by
Cruzelenone, represented by
Hydrogenated zederon represented by
The skin external preparation according to any one of claims 1 to 2, which is one or two or more isolated compounds selected from the group consisting of hydrogenated furanodienone represented by the formula: The skin external preparation according to any one of claims 1 to 3, wherein the isolated compound is about 0.000001 to 1.0 mass%.