WO2017095121A1 - Nouveau composé de pyranone hydroxyle, son procédé de fabrication, et composition cosmétique comprenant ledit composé - Google Patents

Nouveau composé de pyranone hydroxyle, son procédé de fabrication, et composition cosmétique comprenant ledit composé Download PDF

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Publication number
WO2017095121A1
WO2017095121A1 PCT/KR2016/013927 KR2016013927W WO2017095121A1 WO 2017095121 A1 WO2017095121 A1 WO 2017095121A1 KR 2016013927 W KR2016013927 W KR 2016013927W WO 2017095121 A1 WO2017095121 A1 WO 2017095121A1
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WO
WIPO (PCT)
Prior art keywords
compound
formula
hydroxy
present
pyranone
Prior art date
Application number
PCT/KR2016/013927
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English (en)
Korean (ko)
Inventor
노호식
유재원
김용진
Original Assignee
(주)아모레퍼시픽
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020160159460A external-priority patent/KR102634263B1/ko
Application filed by (주)아모레퍼시픽 filed Critical (주)아모레퍼시픽
Priority to JP2018528731A priority Critical patent/JP6758380B2/ja
Priority to US15/780,421 priority patent/US10208009B2/en
Priority to CN201680079689.9A priority patent/CN108495848B/zh
Priority to EP16871017.6A priority patent/EP3385260B1/fr
Publication of WO2017095121A1 publication Critical patent/WO2017095121A1/fr

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Classifications

    • 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
    • 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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
    • C07D309/40—Oxygen atoms attached in positions 3 and 4, e.g. maltol

Definitions

  • the present invention relates to a novel hydroxy pyranone compound having a fat cell differentiation promoting ability, a preparation method thereof, and a cosmetic composition comprising the same as an active ingredient.
  • the basic structure of the skin is maintained by subcutaneous adipose tissue, which acts to influence the volume and strength of the skin. Therefore, in order to maintain and improve the volume and elasticity of the skin, it may be a fundamental solution to increase the volume of adipose tissue rather than to give elasticity to the dermis or epidermis in the outer layer of the skin.
  • preadipocytes It is generally used widely because it has the property of differentiation into adipocytes by differentiation inducing substances such as insulin.
  • mesenchymal stem cells for fat cells.
  • Adipose-derived mesenchymal stem cells can be differentiated using methods similar to those used to differentiate adipocytes into adipocytes ( Exp . Cell Res. 2006, 312, 1856-1864). Widely used ( Science 1999, 284, 143-146).
  • these adipose-derived mesenchymal stem cells are known to be differentiated not only into adipocytes but also into other types of cells such as chondrocytes and bone cells ( J. Cell Sci. 2006 119, 2204-2213) . It is distributed in, and it is thought that the possibility of its use is infinite.
  • the effects for promoting fat cell differentiation are included in the actual cosmetic composition, such that the effect is still insufficient to exhibit sufficient skin volume and elasticity increase effect in the human body, thereby allowing consumers to feel the maximum satisfaction with the cosmetic composition. It was hard to get.
  • the inventors of the present invention after conducting a multi-faceted study on compounds that can improve the effect of promoting the differentiation of fat cells based on the results of the preceding studies described above, hydroxy, Contains the nucleus of 3- (2,6,6-trimethyl-cyclohex-2-enyl) -propenoic acid (3- (2,6,6-timethyl-cyclohex-2-enyl) propenoic acid) in pyranone compounds A novel compound was prepared, and the novel compound was confirmed to enhance the differentiation promoting effect of the adipocytes, thereby completing the present invention.
  • Still another object of the present invention is to provide a method for preparing the novel hydroxy pyranone compound.
  • Another object of the present invention is to provide a cosmetic composition comprising the novel hydroxy pyranone compound as an active ingredient.
  • the present invention provides a hydroxy pyranone compound represented by the following formula (1):
  • the present invention is represented by the following Scheme 1, and provides a method for preparing a hydroxy pyranone compound of Formula 1 prepared by reacting a compound of Formula 2 and a compound of Formula 3:
  • the present invention also provides a cosmetic composition
  • a cosmetic composition comprising the hydroxy pyranone compound represented by the formula (1) as an active ingredient.
  • the hydroxy pyranone compound according to the present invention has an improved fat cell differentiation promoting effect as compared to conventional selenoidoid G or other fat cell differentiation promoting compound.
  • the compound since the compound may exhibit the effect of promoting the differentiation of human mesenchymal stem cells into adipose cells to produce adipose cells to enhance the volume and elasticity of the skin, it is formulated into a variety of cosmetic products to satisfy customers Can improve.
  • the present invention provides a novel hydroxy pyranone compound represented by the following formula (1).
  • the IUPAC name of the hydroxy pyranone compound of Formula 1 is 3- (2,6,6-trimethyl-cyclohex-2-enyl) -propenoic acid 5-hydroxy-4-oxo-4H-pyran-2-ylmethyl Ester (3- (2,6,6-Trimethyl-cyclohex-2-enyl) -propenoic acid 5-hydroxy-4-oxo-4H-pyran-2-ylmethyl ester).
  • the compound of Formula 1 is an off-white solid compound at room temperature.
  • the hydroxy pyranone compound presented in the present invention includes an isomer.
  • “Isomers” in particular are not only optical isomers (eg, essentially pure enantiomers, essentially pure diastereomers or mixtures thereof), but also conformational isomers. ) (Ie, isomers that differ only in the angle of one or more chemical bonds), position isomers (especially tautomers) or geometric isomers (eg, cis-trans isomers).
  • the compound represented by Chemical Formula 1 is prepared by reacting a pyranone compound of Chemical Formula 2 with a cyclohexenyl ester compound of Chemical Formula 3, as shown in Scheme 1 below:
  • the compound of Formula 1 is prepared by a coupling reaction between the halogen element of the pyranone compound and the metal of the cyclohexenyl ester compound.
  • X is a halogen element, wherein the halogen element may be F, Cl, Br, or I, preferably Cl.
  • the compound of formula (2) can be purchased and used commercially available or can be prepared and used directly.
  • 5-hydroxy-2- (chloromethyl) -4H-pyran-4-one in which X is Cl is used, which is 5-hydroxy-2- (hydroxymethyl) -4H-pyran.
  • the 4-one was directly prepared by reacting with thionyl chloride (SOCl 2 ).
  • the cyclohexenyl ester compound of formula 3 is 3- (2,6,6-trimethyl-cyclohex-2-enyl) -propenoic acid (3- (2,6,6-timethyl-cyclohex-2-enyl) propenoic acid), 3- (2,6,6-trimethyl-cyclohex-2-enyl) -propenoic acid (3- (2,6,6-timethyl-cyclohex-2-enyl) propenoic acid)
  • the cation (M + ) is present in the form of a carboxyl group.
  • the cation (M + ) is one kind selected from the group consisting of Li + , Na + , K + .
  • It may be a binder, for example to prepare 3- (2,6,6-trimethyl-cyclohex-2-enyl) -propenoic acid (3- (2,6,6-timethyl-cyclohex-2-enyl) propenoic acid) and sodium hydroxide are dissolved together in methanol and ionized, followed by distillation of methanol.
  • the hydroxy pyranone compound of Formula 1 was prepared through ester linkage of hex-2-enyl) -propenoate (Sodium 3- (2,6,6-timethyl-cyclohex-2-enyl) propenoate).
  • the reaction is not particularly limited in the present invention, it can be carried out under the condition that the halogen-metal coupling reaction can be made sufficiently.
  • the reaction temperature is carried out at reflux temperature of the solvent, for example at 50 to 250 ° C. for 0.5 to 5 hours, preferably 1 to 3 hours.
  • the solvent may be any solvent capable of sufficiently dissolving the compounds of Formulas 2 and 3, for example, N, N-dimethylformamide (N, N-dimethylformamide, DMF), tetrahydrofuran (THF), dimethyl sulfoxide And one selected from the group consisting of aside (DMSO), acetonitrile, dioxane, benzene, toluene, ether, methanol, hexane, cyclohexane, pyridine, N-methylpyrrolidone and combinations thereof, preferably DMF Use
  • N, N-dimethylformamide N, N-dimethylformamide, DMF
  • THF tetrahydrofuran
  • dimethyl sulfoxide dimethyl sulfoxide
  • DMSO dioxane
  • benzene toluene
  • ether methanol
  • hexane cyclohexane
  • pyridine N-methylpyrrolidone and combinations thereof
  • the solvent is distilled and then subjected to a post-treatment process such as washing, drying, and purification to obtain a high purity compound.
  • the hydroxy pyranone compound of Formula 1 according to the present invention is applicable to various fields, and preferably may be used as an active ingredient of the cosmetic composition.
  • the compound of Formula 1 may generate and accumulate fat globules by promoting fat cell differentiation, thereby improving wrinkles and improving elasticity of the skin.
  • the hydroxy pyranone compound When used as an active ingredient in the cosmetic composition, its content varies depending on the formulation, and may be used in 0.001 to 99% by weight. Including the active ingredient in the above range is not only suitable for showing the intended effect of the present invention, but also satisfies both the stability and solubility of the composition, and may be the most efficient in terms of cost-effectiveness.
  • Cosmetic compositions can be prepared in any formulations conventionally prepared in the art, including, for example, solution suspensions, emulsions, pastes, gels, creams, lotions, powders, oils, powder foundations, emulsion foundations, wax foundations And it may be formulated in a spray or the like, but is not limited thereto. More specifically, it may be prepared in the form of a sun cream, a flexible lotion, a convergent lotion, a nourishing lotion, a nourishing cream, a massage cream, an essence, an eye cream, a pack, a spray or a powder.
  • the cosmetic composition according to the present invention is a fatty substance, an organic solvent, a dissolving agent, a thickening agent, a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic type or Nonionic emulsifiers, fillers, metal ion sequestrants, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or any other ingredients commonly used in cosmetics It may include adjuvants commonly used in the cosmetic or dermatology field, such as. Such adjuvants are introduced in amounts generally used in the cosmetic or dermatological arts.
  • the formulation is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. .
  • the formulation is a powder or a spray
  • lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, especially in the case of a spray, additionally chlorofluorohydrocarbon, propane / butane.
  • propellants such as dimethyl ether.
  • solvents, solubilizers or emulsions are used as carrier components, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 Fatty acid esters of butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.
  • a carrier diluent such as water, ethanol or propylene glycol
  • suspending agents such as ethoxylated isostearin alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, Aluminum metahydroxide, bentonite, agar or tracant and the like can be used.
  • Adiponectin is a representative protein hormone secreted by fat cells. These adiponectins have been reported to increase in expression as adipocytes differentiate. Therefore, when treated with a novel compound proposed in the present invention, the adiponectin, which is an indicator of promoting adipocyte differentiation, was measured in the cell culture medium to determine the effect of adipocyte differentiation.
  • Adipocyte differentiation was obtained from human adipose tissue derived mesenchymal stem cells (hAT-MSCs) from Lonza, Inc. Walkersville, MD, USA and cultured according to Lonza's instructions. Adipocyte differentiation was carried out using the method recommended by Lonza, except that troglitazone (TRO) was used instead of indomethacin to induce adipocyte differentiation of adipose derived mesenchymal stem cells.
  • TRO troglitazone
  • IDX a medium for differentiating fat cells
  • IDX a medium for differentiating fat cells
  • DEXA dexamethasone
  • IBMX isobutylmethylxanthine
  • TRO 2M a medium for differentiating fat cells
  • adiponectin ELISA Kit (R & D systems, cat. Corrected as a control). Specific measurement method using adiponectin ELISA Kit is as follows.
  • the capture antibody is reacted in a 96-well plate, washed with a wash buffer solution, and the substances shown in Table 1 are added thereto, followed by reaction at room temperature for 2 hours. Thereafter, washing three times at each step, adding detection antibody, HRP enzyme, substrate solution, and stop solution. React as time. After the final reaction, the absorbance is measured at a wavelength of 450 nm using a spectrophotometer.
  • Table 1 shows the results obtained through the above process.
  • the hydroxy pyranone compound of the formula (1) according to the present invention is excellent in promoting fat cell differentiation, it was confirmed that the cosmetic composition comprising this as an active ingredient can enhance the volume and elasticity of the skin.
  • the formulation examples of the cosmetic composition according to an aspect of the present specification are not limited only to the following examples.
  • Formulation example 2 ( Milk Croissant )
  • Compounding ingredient Content (weight%) Compound of Formula 1 (Example) 1.0 glycerin 3.0 Butylene glycol 3.0 Propylene glycol 3.0 Carboxy Vinyl Polymer 0.1 Beeswax 4.0 Polysorbate 60 1.5 Caprylic / Capric Triglycerides 5.0 Squalane 5.0 Sorbitassquioleate 1.5 Liquid paraffin 0.5 Cetearyl Alcohol 1.0 Triethanolamine 0.2 Preservative, coloring, flavoring Quantity Purified water Remaining amount
  • a nutritious cream was prepared according to a conventional method with the composition shown in Table 4 below.
  • a massage cream was prepared according to a conventional method with the composition shown in Table 5.
  • Compound of Formula 1 (Example) 1.0 Beeswax 10.0 Polysorbate 60 1.5 PEG 60 Cured Castor Oil 2.0 Sorbitan sesquioleate 0.8 Liquid paraffin 40.0 Squalane 5.0 Caprylic / Capric Triglycerides 4.0 glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservative, coloring, flavoring Quantity Purified water Remaining amount

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Dermatology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Cosmetics (AREA)

Abstract

La présente invention concerne un nouveau composé de pyranone hydroxyle, son procédé de fabrication, et une composition cosmétique comprenant ledit composé. Selon la présente invention, le composé de pyranone hydroxyle présente une efficacité nettement améliorée par rapport au matériau classique favorisant la différenciation d'adipocytes, et ainsi, est contenu de préférence comme ingrédient actif dans des cosmétiques pour augmenter le volume dermique ou l'élasticité de la peau.
PCT/KR2016/013927 2015-12-01 2016-11-30 Nouveau composé de pyranone hydroxyle, son procédé de fabrication, et composition cosmétique comprenant ledit composé WO2017095121A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2018528731A JP6758380B2 (ja) 2015-12-01 2016-11-30 新規ヒドロキシピラノン化合物、この製造方法及びこれを含む化粧料組成物
US15/780,421 US10208009B2 (en) 2015-12-01 2016-11-30 Hydroxyl pyranone compound, method for producing same, and cosmetics composition comprising compound
CN201680079689.9A CN108495848B (zh) 2015-12-01 2016-11-30 一种新型的羟基吡喃酮化合物、其制备方法及包含其的化妆品组合物
EP16871017.6A EP3385260B1 (fr) 2015-12-01 2016-11-30 Nouveau composé de pyranone hydroxyle, son procédé de fabrication, et composition cosmétique comprenant ledit composé

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20150169644 2015-12-01
KR10-2015-0169644 2015-12-01
KR1020160159460A KR102634263B1 (ko) 2015-12-01 2016-11-28 신규 히드록시 피라논 화합물, 이의 제조방법 및 이를 포함하는 화장료 조성물
KR10-2016-0159460 2016-11-28

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WO2017095121A1 true WO2017095121A1 (fr) 2017-06-08

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5933207A (ja) * 1982-08-20 1984-02-23 Sansho Seiyaku Kk 色白化粧料
US4990330A (en) * 1987-09-25 1991-02-05 Sansho Seiyaku Co., Ltd. Compositions for topical use having melanin synthesis-inhibiting activity
EP0419901A1 (fr) * 1989-09-14 1991-04-03 Sansho Seiyaku Co., Ltd. Préparation endermique pour application externe
JP2003155283A (ja) * 2001-09-04 2003-05-27 National Institute Of Advanced Industrial & Technology コウジ酸エステルおよびその合成方法
KR100482668B1 (ko) 2002-06-22 2005-04-13 주식회사 태평양 히드록시 피라논 유도체 및 이의 제조방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5933207A (ja) * 1982-08-20 1984-02-23 Sansho Seiyaku Kk 色白化粧料
US4990330A (en) * 1987-09-25 1991-02-05 Sansho Seiyaku Co., Ltd. Compositions for topical use having melanin synthesis-inhibiting activity
EP0419901A1 (fr) * 1989-09-14 1991-04-03 Sansho Seiyaku Co., Ltd. Préparation endermique pour application externe
JP2003155283A (ja) * 2001-09-04 2003-05-27 National Institute Of Advanced Industrial & Technology コウジ酸エステルおよびその合成方法
KR100482668B1 (ko) 2002-06-22 2005-04-13 주식회사 태평양 히드록시 피라논 유도체 및 이의 제조방법

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
EXP. CELL RES., vol. 312, 2006, pages 1856 - 1864
J. CELL SCI., vol. 119, 2006, pages 2204 - 2213
RHO, H. S. ET AL.: "Kojyl Cinnamate Ester Derivatives Promote Adiponectin Production during Adipogenesis in Human Adipose Tissue-derived Mesenchymal Stem Cells", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 24, no. 9, 21 March 2014 (2014-03-21), pages 2141 - 2145, XP055332509 *
SCIENCE, vol. 284, 1999, pages 143 - 146

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