WO2017170713A1 - Agent d'anti-photo-vieillissement - Google Patents

Agent d'anti-photo-vieillissement Download PDF

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WO2017170713A1
WO2017170713A1 PCT/JP2017/012939 JP2017012939W WO2017170713A1 WO 2017170713 A1 WO2017170713 A1 WO 2017170713A1 JP 2017012939 W JP2017012939 W JP 2017012939W WO 2017170713 A1 WO2017170713 A1 WO 2017170713A1
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formula
salt
linear
compound represented
cells
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PCT/JP2017/012939
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English (en)
Japanese (ja)
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吉田　重信
俊太郎 平舘
夕子 中上
進二 山木
藤田　一郎
米田　正
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国立研究開発法人農業・食品産業技術総合研究機構
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Publication of WO2017170713A1 publication Critical patent/WO2017170713A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates to an anti-photoaging agent.
  • This application claims priority based on Japanese Patent Application No. 2016-073713 filed in Japan on March 31, 2016, the contents of which are incorporated herein by reference.
  • Sun rays are known to have various effects on human skin. Sunlight contains light of various wavelengths. Of the sun rays, it is said that ultraviolet rays A (UVA), ultraviolet rays B (UVB), and near infrared rays have an adverse effect on the skin. Although UVA (wavelength 320 nm to 400 nm) has a lower energy amount than UVB (wavelength 280 nm to 320 nm), it reaches the dermis deep in the skin. Long-term skin exposure to UVA causes photoaging such as wrinkles and reduced elasticity.
  • UVA ultraviolet rays A
  • UVB ultraviolet rays B
  • near infrared rays near infrared rays
  • MMP matrix metalloproteinase
  • elastin and hyaluronic acid which are matrix components that form the dermis together with collagen
  • UVA transmits through glass that UVB cannot transmit. For this reason, UVA also reaches the human skin in the room. For these reasons, in recent years, the importance of suppressing adverse effects on the skin caused by UVA has increased.
  • Patent Document 1 describes a cosmetic comprising a combination of titanium oxide particles and zinc oxide particles coated with silica, alumina, or alumina / silica.
  • Patent Document 2 describes an ultraviolet absorbent composition containing an ultraviolet absorbing component extracted from a bacterium belonging to the genus Methylobacterium which is a plant-inhabiting microorganism.
  • the present inventors paid attention to a compound represented by the following formula (I) having UVA absorption ability, and conducted intensive studies. As a result, the present inventors have found that the compound represented by the formula (I) has an action of suppressing the photoaging of the skin caused by exposing the skin to UVA, and completed the present invention. . That is, the present invention adopts the following configuration.
  • R 1 and R 2 are each independently a hydrogen atom, a linear or branched alkyl group having 1 to 5 carbon atoms, or a linear or branched structure having 1 to 5 carbon atoms.
  • R 3 represents a hydrogen atom, a linear or branched alkyl group having 1 to 5 carbon atoms, or 1 to 5 carbon atoms.
  • X represents a hydrogen atom or a linear or branched sugar chain having 1 to 10 sugar molecules.
  • a compound represented by the formula (I) or a salt thereof is a compound represented by the formula (II) in which R 1 and R 2 in the formula (I) are methyl groups, and R 3 and X are hydrogen atoms.
  • R 1 and R 2 are methyl groups
  • R 3 is a hydrogen atom
  • X is a linear sugar chain having 5 sugar molecules. Photoaging agent.
  • the anti-photoaging agent of the present invention contains a compound represented by the formula (I) or a salt thereof.
  • a compound represented by the formula (I) or a salt thereof As a result, when the skin coated with the anti-photoaging agent of the present invention is exposed to UVA, the gene expression of collagen, elastin, and hyaluronic acid as matrix components is promoted and the matrix metalloproteinase as a collagen degrading enzyme is promoted. Suppresses the expression of a gene that produces (MMP). For this reason, in the skin to which the anti-photoaging agent of the present invention is applied, when exposed to UVA, the matrix component in the dermis is less likely to decrease, and wrinkles and a decrease in elasticity associated with the decrease in the matrix component are suppressed. Photoaging is prevented.
  • the anti-photoaging agent of the present invention has UVA absorption ability. Therefore, the anti-photoaging agent of this invention shields skin from UVA when the skin which apply
  • Anti-photoaging agent contains a compound represented by the formula (I) or a salt thereof as an active ingredient.
  • R 1 and R 2 are each independently a hydrogen atom, a linear or branched alkyl group having 1 to 5 carbon atoms, or a linear or branched structure having 1 to 5 carbon atoms.
  • R 3 represents a hydrogen atom, a linear or branched alkyl group having 1 to 5 carbon atoms, or 1 to 5 carbon atoms.
  • X represents a hydrogen atom or a linear or branched sugar chain having 1 to 10 sugar molecules.
  • R 1 represents a hydrogen atom, a linear or branched alkyl group having 1 to 5 carbon atoms, a linear or branched alkoxy group having 1 to 5 carbon atoms, or 1 to 5 carbon atoms.
  • a linear or branched alkenyl group preferably a linear alkyl group having 1 to 5 carbon atoms, a methoxy group, or a vinyl group, and more preferably an alkyl group having 1 to 2 carbon atoms.
  • it is a methyl group.
  • R 2 represents a hydrogen atom, a linear or branched alkyl group having 1 to 5 carbon atoms, a linear or branched alkoxy group having 1 to 5 carbon atoms, or a linear or branched group having 1 to 5 carbon atoms.
  • the alkenyl group is preferably a straight-chain alkyl group having 1 to 5 carbon atoms or a methoxy group, more preferably an alkyl group having 1 to 2 carbon atoms, and most preferably a methyl group. preferable.
  • R 2 is a linear or branched alkenyl group having 1 to 5 carbon atoms, if it is a —CH 2 —C 4 H 7 group, it has an influence on the conjugation of electrons related to the ultraviolet absorption ability. Since there are few, it is preferable.
  • R 3 is a hydrogen atom, a linear or branched alkyl group having 1 to 5 carbon atoms, a linear or branched alkenyl group having 1 to 5 carbon atoms, a hydrogen atom or an alkyl having 1 to 2 carbon atoms It is preferably a group, more preferably a hydrogen atom or a methyl group, and most preferably a hydrogen atom.
  • the carboxyl group possessed by the compound represented by formula (I) may form a salt.
  • the carboxyl group of the compound is preferably a carboxylic acid alkali metal salt or a carboxylic acid amine salt, more preferably a carboxylic acid alkali metal salt, and a carboxylic acid sodium salt. Most preferably it is.
  • X is a hydrogen atom or a linear or branched sugar chain having 1 to 10 sugar molecules, and is preferably a hydrogen atom or a linear sugar chain having 1 to 10 sugar molecules.
  • a straight-chain sugar chain having 3 to 8 sugar molecules is more preferred, and a straight-chain sugar chain having 5 sugar molecules or hydrogen atoms is more preferred.
  • the compound represented by the formula (I) or a salt thereof is particularly a compound represented by the formula (II) or a salt thereof, wherein R 1 and R 2 are methyl groups, and R 3 and X are hydrogen atoms, or R It is preferable that 1 and R 2 are methyl groups, R 3 is a hydrogen atom, and X is a straight-chain sugar chain having 5 sugar molecules or a salt thereof.
  • the sugar molecule may be pyranose or furanose, but is preferably pyranose.
  • R 1 and R 2 are methyl groups
  • R 3 is a hydrogen atom
  • X is a linear sugar chain having 5 sugar molecules, or a salt thereof
  • X is 1,4-glycosidically bonded to each other
  • a compound represented by the formula (III) which is a sugar chain consisting of five hexoses (pyranose) or a salt thereof, and a sugar chain consisting of five hexoses (pyranose) in which X is 1,6-glycosidically bonded to each other.
  • X in the formula (I) is a linear sugar chain composed of five hexoses (pyranose), and the hexoses are 1,4-glycosides
  • a compound or a salt thereof which is a sugar chain in which a bonded part and a 1,6-glycoside bonded part are mixed is preferable.
  • a compound represented by formula (III) or a salt thereof, a compound represented by formula (IV) or a salt thereof, and X in formula (I) is a linear sugar chain composed of five hexoses (pyranose)
  • Two or more kinds may exist as a mixture in which an arbitrary ratio is mixed.
  • the compound represented by the formula (I) or a salt thereof has a plurality of stereoisomers.
  • the compound represented by the formula (I) or a salt thereof includes all these stereoisomers.
  • the compound or salt thereof contained in the anti-photoaging agent of this embodiment has a structure represented by the formula (I). For this reason, it has the solubility with respect to an aqueous solvent, and is excellent in the function which suppresses the photoaging of the skin which arises by exposing skin to UVA, and the function which absorbs the ultraviolet-ray in a UVA area
  • R 1 , R 2 , R 3 , and X are all arranged at positions that do not affect the above-described electron conjugation. For this reason, the excellent ultraviolet absorptivity is similarly obtained regardless of R 1 , R 2 , R 3 , and X in the compound represented by the formula (I) or a salt thereof.
  • Method for producing compound or salt thereof The compound represented by the formula (I) or a salt thereof contained in the anti-photoaging agent of the present embodiment can be produced, for example, by the production method shown below. That is, a step of culturing microorganisms growing on a plant to obtain microbial cells (first step), a step of extracting microbial cells with a solvent to obtain an extract (second step), and formula (I) from the extract And a step (third step) of recovering the compound represented by the formula:
  • the microorganisms cultured in this embodiment are grown on plants.
  • the type of plant from which the microorganism is collected is not particularly limited. Examples of plant types include wheat ears, strawberry leaves, evening primrose petals, and rice leaf sheaths. These plants are preferable because many microorganisms of the genus Methylobacterium that produce the compound represented by the formula (I) or a salt thereof are grown.
  • Examples of the method for collecting microorganisms that grow on the plant from the plant include a method in which the plant is immersed in a phosphate buffer and ground in a mortar to obtain a ground solution containing the microorganism.
  • a conventionally known method can be used as a method for culturing microorganisms.
  • a liquid culture method, a solid culture method, a liquid culture method or a solid culture method may be used, and the types of cells to be cultured. It can be appropriately determined according to the like.
  • the medium used for culturing the microorganism include standard agar medium, L (Lennox) medium, LB (Luria Bertani) medium, NB (Nutrient Broth) medium, PD (potato dextrose) medium, PPD (potato peptone dextrose). ) Medium, TB (Terrific broth) medium, etc. can be used.
  • a microorganism collected from a plant is cultured by a solid culture method, and each microbial cell contained in the microorganism collected from the plant is separated and recovered.
  • a grinding liquid containing microorganisms collected from a plant by the above method is applied (smeared) on the surface of a solid medium and cultured to form colonies.
  • Conventionally known conditions can be adopted as culture conditions for microorganisms in the case of using a solid medium.
  • aerobic conditions can be set at 25 ° C. for 3 to 7 days.
  • the cells forming single colonies are collected by a method of scraping the single colonies appearing on the surface of the solid medium, and the individual cells contained in the microorganisms collected from the plant are separated.
  • Each bacterial cell recovered from a single colony that appears on the surface of the solid medium may be applied to the surface of a new solid medium and cultured (pure culture) for each bacterial cell, if necessary, and recovered. .
  • the presence or absence of ultraviolet absorbing ability is examined by spectrocolorimetric method, absorptiometric method, etc. for each bacterial cell separated and recovered from the microorganisms collected from the plant in this way.
  • cells having ultraviolet absorbing ability are identified.
  • a method for identifying a bacterial cell a conventionally known method such as a method of identifying based on the base sequence of an rRNA gene can be used.
  • the bacterial cells of the genus Methylobacterium are cultured by a liquid culture method.
  • a microorganism belonging to the genus Methylobacterium produces a compound represented by the formula (I) or a salt thereof.
  • the WI-182 strain (strain name), the W-213 strain (strain name), the f11 strain (strain name), and the 24N-25 strain (strain name) described later should be used. Is preferred.
  • These strains are microorganisms that grow on plants, can be increased by culture, and can efficiently produce the compound represented by the formula (I) or a salt thereof.
  • WI-182 strain (strain name) is preferable because it can be easily increased by culture.
  • the cells of the genus Methylobacterium separated and recovered from the microorganisms collected from the plant by the above method are cultured by a liquid culture method.
  • the cells isolated from the microorganisms collected from the plant contain multiple types of Methylobacterium, the highest UV-absorbing ability from the multiple types of Methylobacterium It is preferable to select cells and culture them by a liquid culture method.
  • microorganisms collected from plants are cultured and separated and collected by an individual culture method, and among the obtained bacterial cells, only the cells of the genus Methylobacterium having ultraviolet absorption ability are cultured by a liquid culture method. To do. For this reason, the microbial cell which has the ultraviolet absorption ability contained in the microorganisms extract
  • the culture conditions for the bacterial cells when using a liquid medium.
  • aerobic conditions can be set at 25 ° C. for 3 to 7 days.
  • the liquid medium containing the cells may be cultured while being stirred or shaken, or air is supplied to the liquid medium containing the cells.
  • Bacteria obtained by culturing using a liquid medium can be collected using, for example, a centrifugal separation method, a filtration method, or the like.
  • the cells recovered from the liquid medium may be frozen and vacuum dried, and then extracted with a solvent in the next step, or may be extracted with a solvent in the next step while being recovered.
  • the cells cultured in a liquid medium can be further cultured using a new liquid medium as necessary in order to secure a sufficient amount of the compound represented by formula (I) or a salt thereof. May be recovered from.
  • the cells of the genus Methylobacterium collected by culturing in the first step are extracted with a solvent to obtain an extract.
  • the method for obtaining the extract include the following methods. First, a solvent is added to the cells and stirred, and the compound represented by the formula (I) or a salt thereof is extracted from the cells in the solvent. Next, the solvent containing the cells after extraction is filtered to obtain an extract as a filtrate. Thereafter, the extract is concentrated, frozen and vacuum dried to obtain an extract.
  • the solvent used for bacterial cell extraction include alcohol or a mixed solution of alcohol and water. Among these, as a solvent, it is preferable to use methanol, ethanol, isopropyl alcohol, or a mixed solution of these and water, and it is more preferable to use a mixed solution of methanol and water.
  • (Third step) a step of recovering the compound represented by the formula (I) or a salt thereof, which is the target product, from the extract obtained in the second step.
  • alkali treatment and purification treatment are performed as a step of recovering the target product from the extract.
  • the alkali treatment may be performed before the purification treatment, after the purification treatment, or may be performed together with the purification treatment.
  • Alkali treatment is carried out by bringing the extract into contact with an alkaline solution and further extracting the target product from the extract.
  • the pH of the alkaline solution is preferably 9.0 to 14.0, more preferably 10.0 to 13.0, still more preferably 11.0 to 12.0.
  • Examples of the alkaline solution include a mixed solution of aqueous ammonia and methanol.
  • a conventionally known method can be used, and examples thereof include anion exchange chromatography, cation exchange chromatography, hydrophobic chromatography, affinity chromatography, and reverse phase chromatography. It is done.
  • the purification treatment may be performed by a mixed mode chromatography method in which the above chromatography methods are mixed, or may be performed by a method in which different types of chromatography methods are performed a plurality of times.
  • the cation exchange chromatography method using PORAPAK Rxn CX manufactured by WATERS as the column and the hydrophobic chromatography method using Sunrise C28 manufactured by CHROMANIC TECHNOLOGIES are particularly preferable.
  • Examples of the method of performing the alkali treatment together with the purification treatment include a method of performing the above-described chromatography method using the above-mentioned alkaline solution. Specifically, it is preferable to use a cation exchange chromatography method using PoraPak Rxn CX manufactured by WATERS as a column and recovering components eluted with a mixed solution of aqueous ammonia and methanol, which is an alkaline solution.
  • the compound represented by the formula (I) or a salt thereof, which is the target product is obtained.
  • the target product recovered by the production method of the present embodiment is represented by the formula (I) using LC / MS (liquid chromatography mass spectrometry) analysis, NMR (nuclear magnetic resonance) analysis, X-ray crystal structure analysis, and the like. Can be confirmed.
  • the LC / MS analysis can be performed, for example, under the following conditions.
  • LC liquid chromatography
  • PDA detector SPD-M10A
  • a column temperature 40 ° C.
  • a flow rate of 1.0 ml / minm as a mobile phase, ammonium formate, formic acid aqueous solution, Any one or more selected from formic acid methanol solutions can be used.
  • MS mass spectrometry
  • ESI electrospray ionization
  • the NMR analysis can be performed in heavy water using, for example, AVANCE500 manufactured by BRUKER BIOSPIN.
  • the compound represented by the formula (I) or a salt thereof has ultraviolet absorbing ability and solubility in an aqueous solvent.
  • the compound represented by the formula (I) or a salt thereof has a high absorption peak in the wavelength region of 350 to 360 nm, and is excellent in ultraviolet absorption ability in the UVA region.
  • the compound of the present embodiment or a salt thereof is a mixed solution of any one or more of methanol, ethanol, propanol, acetonitrile, ethylene glycol, propylene glycol, and butanediol and water, an alkali metal, an alkaline earth metal salt, Since it is excellent in solubility in an aqueous solvent such as water, a mixture of at least one of an organic acid and an amino acid and water, when used as a material for an anti-photoaging agent, it can be easily blended using an aqueous solvent.
  • a highly pure compound represented by the formula (I) or a salt thereof can be produced. Therefore, for example, when the compound represented by the formula (I) obtained by the production method of the present embodiment or a salt thereof is used as a material for an anti-photoaging agent, the compound represented by the formula (I) or a salt thereof is used. It is preferable because defects caused by impurities contained are unlikely to occur.
  • the manufacturing method of the compound represented by Formula (I) or its salt is not limited to said method.
  • any one of R 1 , R 2 , R 3 , and X in the formula (I) You may manufacture the compound or its salt represented by the formula (I) from which 1 or more differs.
  • the compound represented by the formula (I) or a salt thereof is chemically used only as a raw material by using only components that are not derived from nature without using those extracted from cells obtained by culturing microorganisms that grow on plants. May be synthesized.
  • the compound represented by the formula (I) or the salt thereof contained in the anti-photoaging agent of the present embodiment may be only one type or two or more types.
  • the anti-photoaging agent of this embodiment may contain only the compound represented by the formula (I) and may not contain a salt of the compound represented by the formula (I), or may be represented by the formula (I). Contains only a salt of the compound and may not contain the compound represented by formula (I), or contains both the compound represented by formula (I) and the salt of the compound represented by formula (I) But you can.
  • the compound represented by the formula (I) or the salt thereof contained in the anti-photoaging agent is two or more, the combination and ratio can be appropriately selected according to the purpose.
  • the anti-photoaging agent of the present embodiment may be a pharmaceutically acceptable carrier or the like as long as it does not impair the effects of the present invention. These components may be contained at a general concentration.
  • the pharmaceutically acceptable carrier is not particularly limited, and examples thereof include excipients, binders, disintegrants, lubricants, emulsifiers, stabilizers, diluents, thickeners, wetting agents, pH adjusting agents, Oils, solvents for injections, etc. can be used.
  • moisturizers feel improvers, surfactants, polymer compounds, thickening / gelling agents, solvents, propellants, antioxidants, reducing agents, oxidizing agents, Preservatives, antibacterial agents, chelating agents, pH adjusters, acids, alkalis, powders, inorganic salts, UV absorbers, whitening agents, vitamins and their derivatives, anti-inflammatory agents, anti-inflammatory agents, hair growth agents, blood circulation promoters , Stimulant, hormones, anti-wrinkle agent, anti-aging agent, squeeze agent, cooling sensation agent, warming sensation agent, wound healing promoter, stimulation mitigation agent, analgesic agent, cell activator, plant / animal / microbe extract, antipruritic agent Agent, exfoliating / dissolving agent, antiperspirant, refreshing agent, astringent, enzyme, nucleic acid, fragrance, pigment, colorant, dye, pigment, water, metal-containing compound, unsaturated monomer, polyhydric alcohol, high Molecular additive, anti
  • Examples of pharmaceutically acceptable carriers and other ingredients include, for example, the 16th revised Japanese Pharmacopoeia, Cosmetic Raw Material Standards Second Edition Commentary (Edited by the Japanese Official Church, Yakuji Nipposha, 1984), non-cosmetic raw material standards Ingredient standards (supervised by the Ministry of Health and Welfare Pharmacy Examination Division, Yakuji Nippo Inc., 1993), supplements for ingredients outside the standard of cosmetic ingredients (supervised by the Ministry of Health and Welfare Pharmacy Examination Division, Yakuji Nipposha, 1993) Supervised by the Bureau of Internal Affairs and Communications, Yakuji Nippo, 1993), Cosmetic Raw Material Dictionary (Nikko Chemicals, 1991), International Cosmetic Inditionary and Handbook 2002 Ninth Edition Vol. 1 to 4, by General raw materials described in CTFA and the like can be used. More specifically, for example, the respective raw materials described in JP 2014-114289 A can be mentioned.
  • the anti-photoaging agent of this embodiment is a mixture of the compound represented by the formula (I) or a salt thereof and other components contained as necessary according to a conventional method (for example, a method described in the Japanese Pharmacopoeia). And can be manufactured by formulation.
  • anti-aging agents include creams, lotions, lotions, emulsions, foundations, packs, foams, skin cleansers, extracts, plasters, ointments, spirits, suspensions, tinctures. And dosage forms such as agents, poultices, liniments, and aerosols.
  • the anti-photoaging agent of this embodiment contains a compound represented by the formula (I) or a salt thereof.
  • the anti-photoaging agent of the present embodiment promotes gene expression of the matrix components collagen, elastin, and hyaluronic acid when the skin to which the anti-photoaging agent is applied is exposed to UVA. It suppresses the expression of a gene that produces a certain matrix metalloprotease (MMP). For this reason, when the skin to which the anti-photoaging agent of this embodiment is applied is exposed to UVA, the matrix component in the dermis is less likely to decrease, and wrinkles and elasticity decreases due to the decrease in the matrix component are suppressed. , Photoaging is prevented.
  • MMP matrix metalloprotease
  • the anti-photoaging agent of this embodiment has UVA absorption ability. Therefore, the anti-photoaging agent of the present embodiment shields the skin from UVA when the skin to which it is applied is exposed to UVA, and effectively suppresses photoaging of the skin due to exposure to UVA. .
  • the conventional ultraviolet shielding agent prevents photoaging due to ultraviolet rays by a function of absorbing and scattering ultraviolet rays physicochemically, and the skin caused by exposing the skin to UVA. It did not have a function of physiologically suppressing photoaging itself.
  • the anti-photoaging agent of the present embodiment when the anti-photoaging agent of the present embodiment is applied to the skin, not only the skin is shielded from UVA, but also the effect of physiologically suppressing skin aging caused by exposing the skin to UVA is obtained. It is done.
  • the matrix component increases in the dermis after the skin is exposed to UVA, and the effect of improving aging can be expected. The above effect is also exhibited when the anti-photoaging agent of this embodiment is applied to the skin after being exposed to UVA.
  • the anti-photoaging agent of the present embodiment contains a compound represented by the formula (I) having a solubility in an aqueous solvent or a salt thereof, it can be produced without using a hydrophobic solvent, and variously depending on applications.
  • the dosage form can be changed.
  • compositions of the anti-photoaging agent of this embodiment include the compositions of Composition Examples 1 to 8 shown in Tables 1 to 5.
  • Example> “1. Collecting microorganisms” Strawberry leaves were immersed in a 10 mM phosphate buffer and ground in a mortar to obtain a ground solution containing microorganisms.
  • each bacterial cell separated and recovered from the microorganisms collected from the plant in this manner was examined for the presence or absence of ultraviolet absorbing ability by absorptiometry.
  • the bacterial cell having the highest ultraviolet absorption ability was identified.
  • the bacterial cells were identified based on the base sequence of the rRNA gene. As a result, the cells were of the genus Methylobacterium. This microbial cell was named WI-182 strain.
  • agar plate media from which the cells of the genus Methylobacterium (WI-182 strain) were obtained were prepared and suspended in each agar plate medium by adding 10 ml of sterile purified water. Obtained. Suspensions obtained from two agar plate media were mixed to prepare a mixed solution, each 2 ml was added to seven 100 ml PD media (manufactured by Difco), and cultured at 25 ° C. for 90 hours under aerobic conditions. 600 ml was collected from a culture cultured in 7 PD media and added to 30 L of PD media (Difco). Then, 15 L / min of air was supplied to the liquid medium while stirring the liquid medium containing the bacterial cells using a stirrer at a rotational speed of 400 rpm, and cultured at 25 ° C. for 7 days.
  • the extract was purified by cation exchange chromatography using an alkaline solution.
  • an extract was added to methanol and dissolved to obtain a methanol solution.
  • the methanol solution was passed through a column (PoraPak Rxn CX manufactured by WATERS) to adsorb the extract on the ion exchange resin.
  • the adsorbed extract components dissolved in the alkaline solution were eluted to obtain an eluate. Thereafter, the eluate was concentrated on a rotary evaporator, frozen and vacuum dried to recover 1.36 g of a tan compound as a crude product.
  • FIG. 1 is a graph showing the relationship between the ultraviolet absorption intensity and elution time of the crude product obtained in the examples.
  • the crude product obtained in the examples had elution times of 3.3 min, 4.3 min, 5.2 min, 16.8 min, and 17.6 min when measured at a UV measurement wavelength of 360 nm.
  • a major peak was detected at the position. It was confirmed that the peaks at elution times of 4.3 min, 16.8 min, and 17.6 min show high absorption peaks in the wavelength region of 350 to 360 nm.
  • Example 1 Normal human fibroblasts (NB1RGB cells) manufactured by RIKEN BioResource Center are seeded in a plastic petri dish at a seeding density of 10,000 cells / cm 2 , and Sigma Dulbecco's Modified Eagle (DMEM) medium containing 10% fetal bovine serum Incubated for 24 hours. Subsequently, the NB1RGB cells were irradiated with 15 J / cm 2 of UVA using a UVA irradiation apparatus manufactured by UVP. Thereafter, the purified product dissolved in 60% ethanol is added to a plastic petri dish so that the concentration of the purified product contained in the culture solution in the DMEM medium is 0.01% by mass, and further cultured for 24 hours. Sample 1 was obtained.
  • DMEM Sigma Dulbecco's Modified Eagle
  • Sample 2 After irradiation with UVA, Sample 2 was obtained in the same manner as Sample 1, except that 60% ethanol was added to the plastic petri dish instead of the purified product dissolved in 60% ethanol.
  • Sample 3 Sample 3 was obtained in the same manner as Sample 2, except that UVA was not irradiated.
  • RNA ribonucleic acid
  • cDNA complementary deoxyribonucleic acid
  • quantitative real-time PCR polymerase chain reaction
  • the expression level of the internal standard gene in the NB1RGB cells of Sample 1 to Sample 3 was quantified in the same manner as the expression levels of the collagen gene, elastin gene, and HAS3 gene in the NB1RGB cells of Sample 1 to Sample 3.
  • GPDH glyceraldehyde-3-phosphate dehydrogenase
  • GAPDH GAPDH (ID: HA067812) manufactured by Takara Bio Inc. was used.
  • GAPDH As a collagen gene amplification primer, COLA1 (ID: HA181818) manufactured by Takara Bio Inc. is used, and as an elastin gene amplification primer, ELA (ID: CH000581) manufactured by Takara Bio Inc. is used, and the HAS3 gene is used.
  • ELA ID: CH000581
  • HAS3 gene As an amplification primer, (ID: HA095624) manufactured by Takara Bio Inc. was used.
  • MMP-1 gene expression suppression effect The purified metal matrix protease-1 (MMP-1) gene expression inhibitory effect of the purified product was examined by the method described below.
  • RNA ribonucleic acid
  • cDNA complementary deoxyribonucleic acid
  • quantitative real-time PCR polymerase chain reaction
  • the MMP-1 gene caused by UVA irradiation was compared to the sample 2 in which the purified product was not added. Is expressed less.

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Abstract

L'invention concerne un agent d'anti-photo-vieillissement qui contient un composé représenté par la formule (I) ou un sel de celui-ci. (Dans la formule (I), R1 et R2 sont un atome d'hydrogène, un groupe alkyle linéaire ou ramifié en C1-5, un groupe alcoxy linéaire ou ramifié en C1-5 ou un groupe alcényle linéaire ou ramifié en C1-5. R3 est un atome d'hydrogène, un groupe alkyle linéaire ou ramifié en C1-5 ou un groupe alcényle linéaire ou ramifié en C1-5. X est un atome d'hydrogène ou une chaîne de sucre linéaire ou ramifiée ayant 1 à 10 molécules de sucre.)
PCT/JP2017/012939 2016-03-31 2017-03-29 Agent d'anti-photo-vieillissement WO2017170713A1 (fr)

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JP2016-073713 2016-03-31
JP2016073713A JP6614448B2 (ja) 2016-03-31 2016-03-31 抗光老化剤

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017186259A (ja) * 2016-03-31 2017-10-12 昭和電工株式会社 抗炎症剤

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH083018A (ja) * 1994-06-20 1996-01-09 Toshimitsu Otomo 皮膚老化防止用化粧料
JP2005298383A (ja) * 2004-04-09 2005-10-27 Kanebo Cosmetics Inc シワ改善剤
JP2009173584A (ja) * 2008-01-25 2009-08-06 Fancl Corp シリビン配糖体含有皮膚外用組成物
JP2010132639A (ja) * 2008-11-10 2010-06-17 Nikko Chemical Co Ltd Ｄｎａ損傷抑制剤及びマトリックスメタロプロテアーゼ−１産生抑制剤
JP2013127027A (ja) * 2011-12-19 2013-06-27 National Institute For Agro-Environmental Science 植物生息微生物由来の紫外線吸収剤組成物
WO2017051875A1 (fr) * 2015-09-24 2017-03-30 昭和電工株式会社 Composé faisant preuve d'une capacité d'absorption du rayonnement ultraviolet ou son sel, son procédé de production, préparation externe pour la peau, et produit cosmétique

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6614449B2 (ja) * 2016-03-31 2019-12-04 国立研究開発法人農業・食品産業技術総合研究機構 抗炎症剤

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH083018A (ja) * 1994-06-20 1996-01-09 Toshimitsu Otomo 皮膚老化防止用化粧料
JP2005298383A (ja) * 2004-04-09 2005-10-27 Kanebo Cosmetics Inc シワ改善剤
JP2009173584A (ja) * 2008-01-25 2009-08-06 Fancl Corp シリビン配糖体含有皮膚外用組成物
JP2010132639A (ja) * 2008-11-10 2010-06-17 Nikko Chemical Co Ltd Ｄｎａ損傷抑制剤及びマトリックスメタロプロテアーゼ−１産生抑制剤
JP2013127027A (ja) * 2011-12-19 2013-06-27 National Institute For Agro-Environmental Science 植物生息微生物由来の紫外線吸収剤組成物
WO2017051875A1 (fr) * 2015-09-24 2017-03-30 昭和電工株式会社 Composé faisant preuve d'une capacité d'absorption du rayonnement ultraviolet ou son sel, son procédé de production, préparation externe pour la peau, et produit cosmétique

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017186259A (ja) * 2016-03-31 2017-10-12 昭和電工株式会社 抗炎症剤

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