JP2009132644A - Acne inflammation inhibitor and skin preparation for external use, containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin preparation for external use such as a cosmetic, by finding out a component suitable for being incorporated into the cosmetic and having an effect of inhibiting acne inflammation, and utilizing the same. <P>SOLUTION: This acne inflammation inhibitor contains an acylated hydroquinone glycoside expressed by general formula (1): R-Su-Hy [wherein, R is a 4C-10C linear monovalent aliphatic acyl group; Su is a saccharide residue; and Hy is a hydroquinone residue] and/or its physiologically acceptable salt as an active ingredient. Also the acne inflammation inhibitor is used as a component of the skin preparation for external use. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a comedy inflammation inhibitor and an external preparation for skin containing the same.

In recent years, acne scars are one of the most frequently treated symptoms in aesthetics and cosmetic surgery. Acne is an inflammation caused by the propagation of bacteria such as Propionibacterium acnes in the pores. This inflammation induces thickening of the inflammatory site, and at the same time, promotes melanin production and deposition by activating melanocytes. To do. Further, in the process of healing inflammation, the activity of collagenase such as MMP1 is usually enhanced and scars are formed (Non-patent Document 1). For scar formation, matrix metalloproteinase type I (MMP1) and type II (MMP2) ) Is known to be involved (Non-Patent Document 2). For these reasons, the development of acne is considered to cause scarring after healing, and is considered to have a great influence on the appearance impression of the skin as a so-called acne scar.
At the site of acne onset, there is a comedone that is a mass of fat and keratin mixed in the pores of the sebaceous follicle. The comedones are a place for the propagation of fungi such as P. acnes, which eventually cause inflammation. That is, in order to suppress the inflammation of comedones, it is important to suppress the growth of bacteria in the comedones. In order to suppress the growth of bacteria, routine treatment is required, and it is desirable to treat by routine operations such as the use of cosmetics.

  In order to suppress inflammation of comedones, it is reported that it is effective to administer a combination of an antibacterial component and an antioxidant component, for example, a combination of tetracycline or ascorbic acid (Non-patent Document 3). ). However, it is not realistic to include antibiotics such as tetracycline in daily cosmetics. Under such circumstances, there has been a demand for discovery of a component that suppresses inflammation of comedones, which is suitable for inclusion in daily-use cosmetics. Furthermore, even when the comedones are inflamed, discovery of a component that suppresses the formation of so-called acne scars as much as possible has been demanded.

On the other hand, some hydroquinone derivatives are known to have an action of eliminating active oxygen (Patent Document 1, Non-Patent Document 4). In addition, it is known that hydroquinone glycosides such as arbutin have a melanin production-inhibiting action and a rough skin improving action (Patent Documents 2 and 3), and are blended in a wide range of cosmetics (Patent Document 4). ). Some acylated arbutins are known to have tyrosinase inhibitory activity (Patent Document 5).
However, the action of hydroquinone glycosides on comedones has not been reported so far.
In addition, 6-O- (3-butenoyl) arbutin, 6-O- (4-pentenoyl) arbutin, 6-O- (5-hexenoyl) arbutin, 6-O- (capryloyl) arbutin, 6-O- (2 -Nonenoyl) arbutin or 6-O- (9-decenoyl) arbutin is a novel compound not described in any literature.

JP-A-10-265386 Japanese Patent Laid-Open No. 06-9366 JP 05-139950 A JP 2004-269523 A International Publication No. 2004/033475 Pamphlet Pillinger M. H., et.al .; J. Immunol .; 2003; 171 (11); 6080-6089 Fujiwara M., et.al .; Br. J. Dermatol .; 2005; 153 (2); 295-300 Bowles W.H .; J Esthet Dent .; 1998; 10 (4); 182-186 Iwai K., et.al .; J Agric Food Chem .; 2004; 52 (15); 4893-4898

  This invention discovers the component which has the effect | action which suppresses the inflammation of comedone suitable for making it contain in cosmetics, and makes it a subject to provide skin external preparations, such as cosmetics, using this.

As a result of intensive research efforts to find a component having an action of suppressing inflammation of comedones, the present inventors have obtained an acylated hydroquinone glycoside represented by the following general formula (1) or a physiologically acceptable product thereof. Has been found to have an antibacterial action of P. acnes and a suppressive action on MMP1 enhancement, and the present invention has been completed. That is, the present invention is as follows.
<1> A comedone inflammation inhibitor comprising, as an active ingredient, an acylated hydroquinone glycoside represented by the following general formula (1) and / or a physiologically acceptable salt thereof.

(In the formula, R represents a straight-chain monovalent aliphatic acyl group having 4 to 10 carbon atoms, Su represents a sugar residue, and Hy represents a hydroquinone residue.)
<2> The comeditis inflammation according to <1>, wherein the acylated hydroquinone glycoside represented by the general formula (1) is an acylated arbutin represented by the following general formula (2): Inhibitor.

(In the formula, R represents a straight-chain monovalent aliphatic acyl group having 4 to 10 carbon atoms.)
<3> In the general formula (1) or (2), the linear and monovalent aliphatic acyl group represented by R has an unsaturated bond, <1> or <2> The comedy inflammation inhibitor described in 1.
<4>
The acylated arbutin represented by the general formula (2) includes 6-O- (3-butenoyl) arbutin, 6-O- (4-pentenoyl) arbutin, 6-O- (5-hexenoyl) arbutin, 6- The comedy inflammation inhibitor according to <2> or <3>, which is O- (capryloyl) arbutin, 6-O- (2-nonenoyl) arbutin or 6-O- (9-decenoyl) arbutin.
<5> A topical skin preparation containing the comeditis inflammation inhibitor according to any one of <1> to <4>.
<6> The external preparation for skin according to <5>, which is used for prevention or improvement of acne.
<7> 6-O- (3-butenoyl) arbutin, 6-O- (4-pentenoyl) arbutin, 6- (5-hexenoyl) arbutin, 6-O- (capryloyl) arbutin, 6
-O- (2-nonenoyl) arbutin or 6-O- (9-decenoyl) arbutin, or a physiologically acceptable salt thereof.

  The comedo inflammation inhibitor of the present invention is excellent in the effect of suppressing comeditis inflammation. Moreover, the comedo inflammation inhibitor of this invention is suitable also for mix | blending with skin external preparations, such as cosmetics. The external preparation for skin containing the comedy inflammation inhibitor of the present invention is effective in preventing or improving acne.

(1) Comedy inflammation inhibitor of the present invention The comedy inflammation inhibitor of the present invention comprises an acylated hydroquinone glycoside represented by the general formula (1) and / or a physiologically acceptable salt thereof as an active ingredient. It is characterized by including.

In the general formula (1), R represents a linear and monovalent aliphatic acyl group having 4 to 10 carbon atoms. Preferably, the acyl group has 7 to 9 carbon atoms. The aliphatic acyl group may have an unsaturated bond or may be saturated, but preferably has an unsaturated bond.
Preferred acyl groups include, for example, butenoyl group, pentanoyl group, hexenoyl group, heptenoyl group, octenoyl group, nonenoyl group, decenoyl group, butanoyl group, hexanoyl group, octanoyl group (capryoyl group), decanoyl group (caprynoyl group), and the like. It can be illustrated. Of these, preferred are 3-butenoyl group, 4-pentenoyl group, 5-hexenoyl group, capryloyl group, 2-nonenoyl group and 9-decenoyl group.

  In the general formula (1), Su represents a sugar residue. The sugar residue may be a monosaccharide residue or a polysaccharide residue. The type of sugar is not particularly limited as long as it is a sugar found in glycosides, for example, a monosaccharide residue such as glucose residue, fructose residue, arabinose residue, galactose residue, rhamnose residue, Preferred examples include polysaccharide residues such as sucrose residue and maltose residue. Among these, monosaccharide residues are preferable, and glucose residues are particularly preferable.

  The acyl group described above is bonded to a sugar residue. The number of acyl groups bonded to the sugar residue may be one per molecule or two or more. Preferred is a form in which one acyl group is bonded per molecule of sugar residue and at least two hydroxyl groups are present.

  In the general formula (1), Hy represents a hydroquinone residue.

Among the acylated hydroquinone glycosides represented by the general formula (1), an acylated arbutin represented by the general formula (2) is particularly preferable.
Among them, 6-O- (3-butenoyl) arbutin, 6-O- (4-pentenoyl) arbutin, 6-O- (5-hexenoyl) arbutin, 6-O- (capryloyl) arbutin, 6-O- (2 Preferred examples include -nonenoyl) arbutin or 6-O- (9-decenoyl) arbutin.

The acylated hydroquinone glycoside represented by the general formula (1) can be obtained, for example, by reacting a hydroquinone glycoside with a fatty acid chloride corresponding to an acyl group in the presence of an alkali.
For example, the acylated arbutin represented by the general formula (2) can be produced by introducing an acyl group into the 6-position hydroxyl group of the glucosyl group of arbutin. The introduction of the acyl group can be obtained by reacting arbutin with a fatty acid chloride corresponding to the acyl group in the presence of an alkali and then purifying the glucosyl group having the acyl group introduced at the 6-position hydroxyl group. For example, as described in Patent Document 5 (WO 2004/033475 pamphlet), a method of reacting arbutin with a fatty acid or a fatty acid ester, particularly preferably a fatty acid vinyl ester, using lipase. Can also be manufactured. Since the production of by-products is small, the latter method using lipase is particularly preferable. As the lipase used in such a production method, alkaline protease derived from the genus Bacillus, lipase derived from Candida antarctica and the like can be preferably exemplified, lipase derived from Candida antactica, especially, lipase type B, A non-aqueous solvent system is particularly preferable because excellent enzyme activity can be obtained.

  The acylated hydroquinone glycoside represented by the general formula (1) can be used as it is as an active ingredient of a comedone inflammation inhibitor, or can be used by forming a salt with an alkali. As the salt of the acylated hydroquinone glycoside represented by the general formula (1), there is no particular limitation as long as it is a physiologically acceptable alkali salt generally known in the field of medicine and cosmetics. For example, alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, organic amine salts such as ammonium salt, triethylamine salt, triethanolamine salt and monoethanolamine salt, lysine Preferred examples include salts and basic amino acid salts such as alginates.

  The acylated hydroquinone glycoside represented by the general formula (1) and physiologically acceptable salts thereof are P.I. It has antibacterial action against bacteria such as acnes, melanin production inhibitory action, and PPM1 inhibitory action.

The comedo inflammation inhibitor of the present invention preferably contains a component that assists this action in addition to the acylated hydroquinone glycoside represented by the general formula (1) and physiologically acceptable salts thereof.
As such a component, a substance having an action of already preventing or improving comeditis inflammation or suppressing worsening of inflammation can be preferably exemplified. Specifically, 4-alkyl resorcinols, ascorbic acid or derivatives thereof can be preferably exemplified. Examples of 4-alkylresorcinols include 4-hexylresorcinol, 4-cyclohexylresorcinol, 4- (1-ethylpropyl) resorcinol and the like. As a derivative of ascorbic acid, for example, glycosides such as 2-glucoside, phosphate esters, sulfate esters and the like can be preferably exemplified.

  In addition, the comedy inflammation inhibitor of the present invention preferably contains an anti-inflammatory component in order to seduce inflammation of the comedones. Preferred examples of such anti-inflammatory components include glycyrrhetinic acid-related substances such as glycyrrhizinate and glycyrrhetinic acid stearyl ester, and tranexamic acid-related substances such as tranexamic acid and tranexamic acid methylamide.

  Moreover, the comeditis inflammation inhibitor of this invention is P.I. In order to eliminate active oxygen generated by bacteria such as acnes, it is also preferable to contain an active oxygen eliminating component. Preferred examples of such active oxygen scavenging components include vitamin Es such as vitamin E nicotinate and δ-tocopherol.

(2) The external preparation for skin of the present invention The external preparation for skin of the present invention is characterized by containing the comedy inflammation inhibitor of the present invention.
The topical skin preparation is a general term for preparations to be applied externally to the skin. Specifically, cosmetics (having an intermediate character between cosmetics for external use such as quasi-drugs and medicinal cosmetics). Examples include skin external medicine, skin external goods and the like. The external preparation for skin of the present invention is preferably a cosmetic. This is because the comedones are formed but there is no inflammation, so the disease may not be diagnosed. In such cases, daily treatment with cosmetics is convenient and effective to prevent inflammation of the comedones. Because. Of course, a skin external medicine administered for the purpose of treating or improving the inflammation (acne) of comedones also fully utilizes the action of the comedy inflammation inhibitor of the present invention, and is included in the technical scope of the present invention. .

The content of the comedy inflammation inhibitor in the external preparation for skin of the present invention is preferably 0 as the content of the acylated hydroquinone glycoside represented by the general formula (1) and / or a physiologically acceptable salt thereof. 0.01 to 10% by mass, more preferably 0.1 to 5% by mass.
When the comeditis inflammation inhibitor contains 4-alkylresorcinols, ascorbic acid or a derivative thereof, active oxygen scavenging component, anti-inflammatory component, etc., the content of 4-alkylresorcinol is 0.1 to 1% by mass, Ascorbic acid or its derivative content is 1-10% by mass, active oxygen elimination component content is 0.01-1% by mass, anti-inflammatory component content is 0.01-5% by mass, It is also possible to adjust the content of the comeditis inflammation inhibitor.

  The use of the skin external preparation of the present invention is not particularly limited, but it is particularly preferable to prevent or improve acne. The external preparation for skin of the present invention is preferably used for purposes other than tyrosinase inhibition or whitening.

  The dosage form of the external preparation for skin of the present invention is not particularly limited as long as it is a dosage form used in cosmetics and external pharmaceutical compositions for skin. For example, a lotion dosage form, an emulsion dosage form, a cream dosage form, an oil gel dosage form, an aqueous gel dosage form and the like can be particularly preferably exemplified.

The skin external preparation of this invention can contain the arbitrary component normally used with a skin external preparation other than the said comedone inflammation inhibitor. Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil Oil, wax, oil such as beeswax, canola wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum , Hydrocarbons such as microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl Higher alcohols such as alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, malic acid Diisostearyl, di-2-ethylhexanoic acid ethylene glycol, dicaprate neopentyl glycol, di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, tri Synthetic ester oils such as trimethylolpropane isostearate and pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, methylphenylpoly Linear polysiloxanes such as oxane and diphenylpolysiloxane; cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, Oil agents such as silicone oils such as modified polysiloxanes such as fluorine-modified polysiloxanes; Anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine ether of alkyl sulfates; Cationic surfactants such as stearyltrimethylammonium, benzalkonium chloride, laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imida Zolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), and amphoteric surfactants such as acylmethyltaurine; sorbitan fatty acid esters (sorbitan) Monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (glyceryl monostearate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hardened castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-sorbitol monolaurate, etc.), POE glycerin fatty acid ester Tells (POE-glycerol monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkyl phenyl ethers (POE nonylphenyl) Ethers, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), Nonionic surfactants such as sucrose fatty acid ester and alkyl glucoside; polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene Polyhydric alcohols such as recall, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1,2-octanediol; sodium pyrrolidonecarboxylate Moisturizing ingredients such as lactic acid and sodium lactate; powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, barium sulfate, etc. whose surface may be treated Body, the surface may be treated, inorganic pigments such as bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide; surface may be treated, mica Pearl agents such as titanium, fish phosphorus foil, bismuth oxychloride; red 202 which may be raked, red Color 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue 1 No., Green 201, Purple 201, Red 204, etc .; Organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; Paraaminobenzoic acid UV absorbers; Anthranils Acid UV absorbers; salicylic acid UV absorbers; cinnamic acid UV absorbers; benzophenone UV absorbers; sugar UV absorbers; 2- (2′-hydroxy-5′-t-octylphenyl) benzo UV absorbers such as triazole and 4-methoxy-4′-t-butyldibenzoylmethane; lower alcohols such as ethanol and isopropanol Cole; Vitamin B such as vitamin A or a derivative thereof, vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₂ or a derivative thereof, vitamin B ₁₂ , vitamin B ₁₅ or a derivative thereof; Vitamin E such as α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E acetate, vitamin D, vitamin H, pantothenic acid, pantethine, pyrroloquinoline quinone and the like; antibacterial agents such as phenoxyethanol are preferred It can be illustrated.

  In addition, when the external preparation for skin of the present invention is used as an external preparation for skin, such as for the improvement of comeditis inflammation and for the treatment of acne, an antibiotic can also be contained. As the antibiotic, tetracyclines such as clindamycin, tetracycline, doxycycline and minomycin can be preferably exemplified, and the content thereof is preferably 1 to 5% by mass.

  The external preparation for skin of the present invention can be produced by treating a comeditis inflammation inhibitor and an optional component according to a conventional method.

  Hereinafter, the present invention will be described in more detail with reference to examples, but it is needless to say that the present invention is not limited to such examples.

To 1.5 g of arbutin, 1.9 g of 3-butenoic acid, 1.35 ml of dimethyl sulfoxide, 12 ml of dioxane, 0.36 g of “Novozyme 435” (Novozyme) and 1.35 g of molecular sieve 4A were added, and 35 ° C. and 130 rpm. And stirred for 3 days. The conversion rate was 40%. When the product was examined by TLC, it was found that only a monoester was formed. After the enzyme reaction solution was filtered to remove the enzyme powder, the reaction solution was concentrated under reduced pressure, added to a column packed with 25 g of silica gel, and eluted with hexane: ethyl acetate (1: 1). Collected and concentrated to give 6-O- (3-butenoyl) arbutin (Compound 1). The NMR chart of Compound 1 is shown in FIG.

  The same treatment was carried out by replacing 3-butenoic acid in Example 1 with 4-pentenoic acid to obtain 6-O- (4-pentenoyl) arbutin (compound 2). The NMR chart of Compound 2 is shown in FIG.

  The same treatment was conducted by replacing 3-butenoic acid in Example 1 with 5-hexenoic acid to obtain 6-O- (5-hexenoyl) arbutin (Compound 3). The NMR chart of Compound 3 is shown in FIG.

  The same treatment was carried out by replacing 3-butenoic acid in Example 1 with caprylic acid to obtain 6-O- (capryloyl) arbutin (compound 4). The NMR chart of Compound 4 is shown in FIG.

  The same treatment was carried out by replacing 3-butenoic acid in Example 1 with 2-nonenoic acid to obtain 6-O- (2-nonenoyl) arbutin (Compound 5). The NMR chart of Compound 5 is shown in FIG.

  The same treatment was carried out by replacing 3-butenoic acid in Example 1 with 9-decenoic acid to obtain 6-O- (9-decenoyl) arbutin (Compound 6). The NMR chart of Compound 6 is shown in FIG.

<Test Example 1>
For compounds 2, 4-6, P.I. The antibacterial action against acnes was confirmed by the pulp disk method. That is, a 0.2% agar solution autoclaved on a normal agar plate medium was adjusted to 60 ° C., coated, and pre-cultured for 3 days. acnes was seeded. A 6 mmφ filter paper impregnated with 20 μL of an ethanol solution containing 50 mg / mL of various specimens was placed thereon, and cultured overnight at 37 ° C. The inhibition circle formed around the filter paper was identified and scored according to the following criteria. In other words, when there is no clear stop circle-when forming an obscure stop circle of 2 mm or less +, a clear but positive stop circle with a width of 2 mm or less +, and the width of the stop circle exceeds 2 mm In the case of 4 mm or less, ++, and in the case where the width of the blocking circle exceeds 4 mm and 5 mm or less, it is +++. For comparison, filter paper impregnated with ethanol (control), filter paper impregnated with 6-O-undecanoyl arbutin (Comparative Compound 1), and filter paper impregnated with arbutin (Comparative Compound 2) were also examined. The results are shown in Table 1. From this, the acylated hydroquinone glycoside represented by the general formula (1) is an excellent P.I. It was found to have an antibacterial action against acnes. On the other hand, it was also found that the antibacterial action of acylated arbutin is affected by the carbon number of the acyl group, and that the antibacterial action of acylated arbutin is exhibited when the carbon number of the acyl group is 4-10.

<Test Example 2>
The compounds of Examples 1 to 6 were evaluated for cytotoxicity and melanin production inhibitory action. That is, using a 24-well plate, seeded with normal human epidermal melanocytes (manufactured by Kurashiki Boseki Co., Ltd.) at a concentration of 4.5 × 10 ⁴ cells / cm ² and cultured at 37 ° C. for 24 hours in a carbon dioxide atmosphere. It was. The target compound dissolved in DMSO and added to the medium was replaced with the medium of the previous day. Cytotoxicity was evaluated by observing the ratio of viable and dead cells on a hemocytometer after cells were collected by trypsin treatment after further culturing for 2 days and stained with 0.5% trypan blue. Regarding the melanin production inhibitory action, when the medium containing the target compound is replaced, 0.25 μCi (microcurie) of ¹⁴ C-labeled thiouracil that is specifically taken up into the cell during the melanin synthesis process of the cell is added. The culture was performed for 2 days in the same manner as the culture conditions. The culture solution is removed from each well, washed with PBS (phosphate buffered saline), and then 50 μL of trichloroacetic acid (TCA) is added to lyse the cells. After the cells were completely lysed, 500 μL of water was added, and all liquid components in the wells were transferred to a tube, allowed to stand under ice cooling for 15 minutes or more, and then centrifuged at 15000 rpm for 5 minutes. The supernatant was removed from the tube after centrifugation, 500 μL of 10% TCA was added again, and the mixture was allowed to stand for 15 minutes or longer under ice cooling. Then, it centrifuged for 5 minutes at 15000 rpm. The supernatant was removed again, 1 mL of Aquasol-2 (Perkin Elmer) was added as a scintillator, and the radiation dose was measured with a liquid scintillation counter (LSC-6100: Aloka). As a control, a sample not containing the compound was prepared in the same manner as described above, and the percentage of the radiation dose of each compound relative to the control was determined to obtain the melanin amount (%). The criterion for observation is that regarding cell viability, if the cell death rate is 50% or more, it is determined that the cell is cytotoxic, and if it is less than 50%, it is determined that there is no cytotoxicity. When it was 50% or less with respect to the control, it was judged effective, and when it was larger than 50%, it was judged invalid. The results are shown in Table 2. This shows that the compound of the present invention has little cytotoxicity and is excellent in melanin production inhibitory action. Comparative compound 1 (6-undecanoyl arbutin) and comparative compound 2 (arbutin) were similarly examined. In Comparative Compound 1, the melanin production inhibitory action was determined to be effective, but it was determined to be cytotoxic.
From this, it was found that the acylated hydroquinone glycoside represented by the general formula (1) has no cytotoxicity and has an excellent inhibitory effect on melanin production.

<Test Example 3>
Compound 1 was tested for inhibitory action on MMP1. That is, MMP1 activity in the presence and absence of Compound 1 was measured using “MMP-1 Assay Kit for Drug Discovery, Colorimetric, QuantiZyme” (manufactured by Biomol International). The MMP1 activity in the presence of Compound 1 was 104.7% when the concentration of Compound 1 was 1 mM and 108.3% when 0.1 mM, compared to that in the absence of Compound. From this, it was found that the acylated hydroquinone glycoside represented by the general formula (1) also has an action of suppressing the enhancement of MMP1.

  According to the formulation shown below, cosmetics 1 to 6, which are external preparations for skin of the present invention, were produced. That is, the components of (a) and (b) were each heated to 80 ° C., and (b) was gradually added to a under stirring, the emulsion was homogenized with a homomixer, and then stirred and cooled to obtain a cosmetic.

  The present invention can be applied to an external preparation for skin such as cosmetics. In particular, it is suitable for cosmetics for preventing or improving acne.

1 is a diagram showing an NMR chart of Compound 1. FIG. 2 is a diagram showing an NMR chart of Compound 2. FIG. 4 is a diagram showing an NMR chart of Compound 3. FIG. 4 is a diagram showing an NMR chart of Compound 4. FIG. 4 is a diagram showing an NMR chart of Compound 5. FIG. 2 is a diagram showing an NMR chart of Compound 6. FIG.

Claims (7)

A comedy inflammation inhibitor comprising, as an active ingredient, an acylated hydroquinone glycoside represented by the following general formula (1) and / or a physiologically acceptable salt thereof.

(In the formula, R represents a straight-chain monovalent aliphatic acyl group having 4 to 10 carbon atoms, Su represents a sugar residue, and Hy represents a hydroquinone residue.) The comedy inflammation inhibitor according to claim 1, wherein the acylated hydroquinone glycoside represented by the general formula (1) is an acylated arbutin represented by the following general formula (2).

(In the formula, R represents a straight-chain monovalent aliphatic acyl group having 4 to 10 carbon atoms.)   The comeditis inflammation according to claim 1 or 2, wherein in the general formula (1) or (2), the linear monovalent aliphatic acyl group represented by R has an unsaturated bond. Inhibitor.   The acylated arbutin represented by the general formula (2) includes 6-O- (3-butenoyl) arbutin, 6-O- (4-pentenoyl) arbutin, 6-O- (5-hexenoyl) arbutin, 6- It is O- (capryloyl) arbutin, 6-O- (2-nonenoyl) arbutin or 6-O- (9-decenoyl) arbutin, The comeditis inflammation inhibitor of Claim 2 or 3 characterized by the above-mentioned.   The skin external preparation containing the comedone inflammation inhibitor of any one of Claims 1-4.   The skin external preparation according to claim 5, which is used for prevention or improvement of acne.   6-O- (3-butenoyl) arbutin, 6-O- (4-pentenoyl) arbutin, 6- (5-hexenoyl) arbutin, 6-O- (capryloyl) arbutin, 6-O- (2-nonenoyl) arbutin Or 6-O- (9-decenoyl) arbutin, or a physiologically acceptable salt thereof.

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