WO2022080765A1 - Composition de blanchiment de la peau contenant un dimère dihydrofuran-2(3h)-one - Google Patents

Composition de blanchiment de la peau contenant un dimère dihydrofuran-2(3h)-one Download PDF

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WO2022080765A1
WO2022080765A1 PCT/KR2021/013839 KR2021013839W WO2022080765A1 WO 2022080765 A1 WO2022080765 A1 WO 2022080765A1 KR 2021013839 W KR2021013839 W KR 2021013839W WO 2022080765 A1 WO2022080765 A1 WO 2022080765A1
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alkyl
formula
integer
skin whitening
alkynyl
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윤청용
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주식회사 에피바이오텍
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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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/32—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/58—One oxygen atom, e.g. butenolide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/30—Other Organic compounds

Definitions

  • the present invention relates to a skin whitening composition
  • a skin whitening composition comprising a dihydrofuran-2(3H)-one dimer having melanogenesis inhibitory activity, or a pharmaceutically acceptable salt thereof.
  • the compound of the present invention acts on the melanin biosynthesis signaling pathway induced by ⁇ -MSH (Melanocyte-stimulating hormone), and has an excellent effect of preventing or treating diseases of melanogenesis hyper-deposition.
  • Melanin is a black pigment found in animals, plants, and microorganisms that is not essential for growth or development, but it is a substance that increases viability and competitiveness in the environment.
  • Melanin is a stable pigment among the pigments found in living organisms, and is insoluble in almost all solvents, and the process of melanogenesis takes place in melanosomes, which are organelles of melanocytes, which are specially differentiated cells. It is known That is, skin color is determined according to the content and distribution of melanin, and is related to the number and distribution of melanosomes that are generated in melanocytes and released to the outside of cells.
  • Melanin exists in the skin and plays an important role in protecting the body from UV rays, but when melanin is excessively produced, it promotes pigmentation and skin aging, and causes hyperpigmentation such as spots and freckles and melanoma. known to be an important factor.
  • a person's skin color is determined by several factors, such as the activity of melanocytes that make melanin pigment, the distribution of blood vessels, the thickness of the skin, and the presence or absence of internal and external pigments such as carotenoids and bilirubin.
  • melanin the black pigment
  • melanin the black pigment
  • the formation of melanin is influenced by genetic factors, hormone secretion, physiological factors related to stress, etc., and environmental factors such as UV irradiation.
  • Melanin pigment is produced in melanocytes and then moves to keratinocytes to protect the skin from harmful environmental stimuli such as UV radiation.
  • Ultraviolet rays from the sun are UVA in the 320 - 400nm region, depending on the wavelength; UVB in the region of 280 - 320 nm; And it can be classified into UVC of 200 - 280nm region, of which UVB causes the production of melanin.
  • UVB induces melanin production through a complex process through the interaction between keratinocytes and melanocytes, or is a major regulator of melanin production through phosphorylation of Ser133 of CREB (cAMP-response element-binding protein) by increasing cAMP. It increases the production of melanin through a method of increasing the expression of MITF (Microphthalmia-associated transcription factor).
  • keratinocytes When exposed to UVB, keratinocytes secrete paracrine factor to promote melanogenesis in melanocytes.
  • paracrine factors Among the paracrine factors secreted, the most important agonist to stimulate melanogenesis is ⁇ -melanocytes. It is ⁇ -melanocyte stimulating hormone ( ⁇ -MSH).
  • vitamin C and its derivatives have been used for the purpose of inhibiting melanin production, but these also have a problem in that they have low tyrosinase inhibitory activity.
  • dihydrofuran-2(3H)-one dimer is ⁇ -melanocyte stimulating hormone ( ⁇ -Melanocyte stimulating hormone, ⁇ -MSH) was confirmed to exhibit an excellent effect in promoting the decomposition of melanosomes.
  • Patent Document 1 Korean Patent No. 1890058
  • the present inventors have completed the present invention by confirming that the dihydrofuran-2(3H)-one dimer has an excellent effect as a result of research to develop a material having the effect of inhibiting melanogenesis and promoting the decomposition of melanosomes .
  • An object of the present invention is to provide a composition for skin whitening comprising, as an active ingredient, a dihydrofuran-2(3H)-one dimer, or a pharmaceutically acceptable salt thereof, which inhibits melanogenesis and promotes melanosome decomposition. do it with
  • the present invention provides a novel compound of dihydrofuran-2(3H)-one dimer having the effect of inhibiting melanogenesis and promoting melanosome degradation.
  • the present invention provides a composition comprising a dimer of dihydrofuran-2(3H)-one of formula (I), an isomer thereof, or a pharmaceutically acceptable salt thereof:
  • R 1 and R 3 are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
  • R 2 and R 4 are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, halo, hydroxy, C 1 -C 6 alkoxy, cyano, or —OR a ;
  • R a is Si unsubstituted or substituted with -C(O)R b or C 1 -C 6 alkyl;
  • R b is hydrogen or C 1 -C 6 alkyl
  • n 1 to 20.
  • the present invention provides a composition comprising a dimer of dihydrofuran-2(3H)-one of formula II, an isomer thereof, or a pharmaceutically acceptable salt thereof:
  • n is an integer from 1 to 20;
  • the present invention provides a composition comprising a dimer of dihydrofuran-2(3H)-one of formula III, an isomer thereof, or a pharmaceutically acceptable salt thereof:
  • n is an integer from 1 to 20.
  • the present invention provides a cosmetic composition for skin whitening, or a health functional food, comprising the compound of the present invention.
  • the present invention provides a pharmaceutical composition for the treatment or prevention of melanin hyperpigmentation disease comprising the compound of the present invention.
  • the present invention provides a novel compound of a compound represented by the following formula (I), an isomer thereof, or a pharmaceutically acceptable salt thereof.
  • R 1 and R 3 are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
  • R 2 and R 4 are each independently hydrogen, C One -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 Alkynyl, Halo, C One -C 6 Alkoxy, cyano, or -OR a ego;
  • R a is Si unsubstituted or substituted with -C(O)R b or C 1 -C 6 alkyl;
  • R b is hydrogen or C 1 -C 6 alkyl
  • n 1 to 20.
  • the present invention provides a novel compound of a dimer, an isomer thereof, or a pharmaceutically acceptable salt thereof of dihydrofuran-2(3H)-one of the following formula (II).
  • n is an integer from 1 to 20;
  • the dimer of dihydrofuran-2(3H)-one of the present invention does not have cytotoxicity and inhibits melanin production, so it is useful for skin whitening or improving, preventing or treating diseases of melanin hyperpigmentation.
  • the dimer of the present dihydrofuran-2(3H)-one has a significantly superior effect compared to that of the monomer.
  • Figure 2 shows the melanin production inhibitory effect according to the treatment concentration of the compound of Formula 2 (WJC-2020-68).
  • Figure 3 shows the melanin production inhibitory effect according to the treatment concentration of the compounds of Formulas 5 to 7 (WJC-2020-69).
  • Figure 4 shows the melanin production inhibitory effect according to the treatment concentration of the compounds of Formulas 3 to 5 (WJC-2020-70).
  • Figure 5 shows the melanin production inhibitory effect according to the treatment concentration of arbutin (Arbutin).
  • FIG. 6 shows the survival rate (%) of B16 melanoma (melanoma) cells according to the treatment concentration of the compound of Formula 1 (WJC-2020-67).
  • Figure 10 shows the survival rate (%) of B16 melanoma (melanoma) cells according to the treatment concentration of arbutin (Arbutin).
  • the present invention relates to a composition
  • a composition comprising a dimer, an isomer thereof, or a pharmaceutically acceptable salt thereof of dihydrofuran-2(3H)-one of the following formula (I).
  • R 1 and R 3 are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
  • R 2 and R 4 are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, halo, hydroxy, C 1 -C 6 alkoxy, cyano, or —OR a ;
  • R a is Si unsubstituted or substituted with -C(O)R b or C 1 -C 6 alkyl;
  • R b is hydrogen or C 1 -C 6 alkyl
  • n is an integer from 1 to 20;
  • the present invention provides
  • R1 and R3 are each independently C 1 -C 6 alkyl
  • R 2 and R 4 are each independently hydrogen or hydroxy
  • n may be an integer from 1 to 20 in the composition.
  • n is preferably an integer of 5 to 15, and more preferably an integer of 8 to 12.
  • the present invention is a composition comprising a compound represented by the following formula (II), an isomer thereof, or a pharmaceutically acceptable salt thereof.
  • n may be an integer from 1 to 20 in the composition.
  • n is preferably an integer of 5 to 15, and more preferably an integer of 8 to 12.
  • the present invention is a composition comprising a compound represented by the following formula (III), an isomer thereof, or a pharmaceutically acceptable salt thereof.
  • n is an integer of 1 to 20, preferably an integer of 5 to 15, and more preferably an integer of 8 to 12.
  • the present invention may be a cosmetic composition for skin whitening comprising the compound of the present invention, or a health functional food.
  • the present invention may be a pharmaceutical composition for the treatment or prevention of melanin hyperpigmentation disease comprising the compound of the present invention.
  • the compound of the present invention inhibits melanogenesis or promotes melanosome degradation, and may be, for example, acting on a melanin biosynthesis signaling pathway induced by ⁇ -MSH.
  • the "melanin hyperpigmentation disease" of the present invention may be melasma, freckles, spots, solar surplus, drug pigmentation, inflammatory pigmentation, senile pigmentation, or gestational pigmentation, but is not limited thereto.
  • composition of the present invention has a whitening effect, hydroquinone (hydroquinone, Benzene-1,4-diol), mulberry extract, arbutin, ethyl ascorbyl ether, oil-soluble licorice extract, ascorbyl glucoside, magnesium ascorbyl phosphate, niacinamide, Alpha-bisabolol or ascorbyltetraisopalmitate may be further included.
  • hydroquinone hydroquinone, Benzene-1,4-diol
  • mulberry extract arbutin
  • ethyl ascorbyl ether oil-soluble licorice extract
  • ascorbyl glucoside oil-soluble licorice extract
  • magnesium ascorbyl phosphate niacinamide
  • Alpha-bisabolol or ascorbyltetraisopalmitate may be further included.
  • the present invention relates to a compound represented by the following formula (I), an isomer thereof, or a pharmaceutically acceptable salt thereof.
  • R 1 and R 3 are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
  • R 2 and R 4 are each independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, halo, C 1 -C 6 alkoxy, cyano, or —OR a ;
  • R a is Si unsubstituted or substituted with -C(O)R b or C 1 -C 6 alkyl;
  • R b is hydrogen or C 1 -C 6 alkyl
  • n may be an integer from 1 to 20 in the composition.
  • n is preferably an integer of 5 to 15, and more preferably an integer of 8 to 12.
  • the present invention relates to a compound represented by the following formula (II), an isomer thereof, or a pharmaceutically acceptable salt thereof.
  • n may be an integer from 1 to 20 in the composition.
  • n is preferably an integer of 5 to 15, and more preferably an integer of 8 to 12.
  • alkyl is a hydrocarbon having primary, secondary, tertiary or quaternary carbon atoms and includes saturated aliphatic groups which may be straight-chain, branched or cyclic, or combinations thereof.
  • an alkyl group has 1 to 20 carbon atoms (ie, C 1 -C 20 alkyl), 1 to 10 carbon atoms (ie, C 1 -C 10 alkyl), or 1 to 6 carbon atoms (ie, C 1 -C 10 alkyl). C 1 -C 6 alkyl).
  • alkyl refers to C 1 -C 6 alkyl.
  • alkyl groups examples include methyl (Me, —CH 3 ), ethyl (Et, —CH 2 CH 3 ), 1-propyl (n-Pr, n-propyl, —CH 2 CH 2 CH 3 ), 2-propyl ( i-Pr, i-propyl, -CH(CH 3 ) 2 ), 1-butyl (n-Bu, n-butyl, -CH 2 CH 2 CH 2 CH 3 ), 2-methyl-1-propyl (i- Bu, i-butyl, -CH 2 CH(CH 3 ) 2 ), 2-butyl (s-Bu, s-butyl, -CH(CH 3 )CH 2 CH 3 ), 2-methyl-2-propyl (t -Bu, t-butyl, -C(CH 3 ) 3 ), 1-pentyl (n-pentyl, -CH 2 CH 2 CH 2 CH 3 ), 2-pentyl (-CH(CH 3 )CH
  • alkyl as used throughout the specification, examples and claims is intended to include both unsubstituted and substituted alkyl groups, the latter of which are trifluoromethyl and 2,2,2-trifluoromethyl.
  • alkyl moiety having a substituent replacing a hydrogen on one or more carbons of the hydrocarbon backbone including haloalkyl groups such as roethyl, and the like.
  • C xy or "C x -C y " when used in conjunction with a chemical moiety such as alkyl, alkenyl, alkynyl or alkoxy is intended to include groups containing from x to y carbons in the chain.
  • C 0 alkyl represents hydrogen when the group is in a terminal position and a bond when internal to the group.
  • a C 1 -C 6 alkyl group contains 1 to 6 carbon atoms in the chain.
  • Alkoxy refers to a group having the formula —O-alkyl, wherein the alkyl group as defined above is attached to the parent compound through an oxygen atom.
  • the alkyl moiety of the alkoxy group may be, for example, 1 to 20 carbon atoms (ie C 1 -C 20 alkoxy), 1 to 12 carbon atoms (ie C 1 -C 12 alkoxy), 1 to 10 carbon atoms. (ie, C 1 -C 10 alkoxy), or 1 to 6 carbon atoms (ie, C 1 -C 6 alkoxy).
  • alkoxy groups include methoxy (-O-CH 3 or -OMe), ethoxy (-OCH 2 CH 3 or -OEt), and t-butoxy (-OC(CH 3 ) 3 or -O-tBu ), but is not limited thereto.
  • Alkenyl has primary, secondary, tertiary or quaternary carbon atoms, includes straight-chain, branched and cyclic groups, or combinations thereof, and includes one or more regions of unsaturation, i.e., carbon-carbon sp It is a hydrocarbon with two double bonds.
  • an alkenyl group has 2 to 20 carbon atoms (ie, C 2 -C 20 alkenyl), 2 to 12 carbon atoms (ie, C 2 -C 12 alkenyl), 2 to 10 carbon atoms ( ie, C 2 -C 10 alkenyl), or 2 to 6 carbon atoms (ie, C 2 -C 6 alkenyl).
  • Alkynyl is a hydrocarbon having primary, secondary, tertiary or quaternary carbon atoms, including straight-chain, branched and cyclic groups, or combinations thereof, and having at least one carbon-carbon sp triple bond. am.
  • an alkynyl group has 2 to 20 carbon atoms (ie, C 2 -C 20 alkynyl), 2 to 12 carbon atoms (ie, C 2 -C 12 alkynyl), 2 to 10 carbon atoms ( ie, C 2 -C 10 alkynyl), or 2 to 6 carbon atoms (ie, C 2 -C 6 alkynyl).
  • suitable alkynyl groups include, but are not limited to, acetylenic (-C ⁇ CH) and propargyl (-CH 2 C ⁇ CH).
  • halo includes chloro, fluoro, bromo, and iodo.
  • pharmaceutically acceptable salt refers to a salt according to an aspect of the present invention that is pharmaceutically acceptable and has the desired pharmacological activity of the parent compound.
  • pharmaceutically acceptable salts herein are intended to refer to all salts that can be used in pharmaceutical compositions as well as cosmetic compositions or food compositions.
  • the salt is not particularly limited as long as it is pharmaceutically acceptable, and for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, methanesulfonic acid , benzenesulfonic acid, toluenesulfonic acid, naphthalenesulfonic acid, and the like can be used.
  • the cosmetic composition of the present invention is, for example, a solution, a gel, a solid or kneaded anhydrous product, an emulsion obtained by dispersing an oil phase in an aqueous phase, a suspension, a microemulsion, a microcapsule, microgranule or ionic (liposome), non-ionic type. It may be provided in the form of a vesicular dispersant, cream, skin, lotion, powder, ointment, spray or in the form of a cone stick. In addition, it may be prepared in the form of a foam or an aerosol composition further containing a compressed propellant.
  • the cosmetic composition includes a fatty substance, an organic solvent, a solubilizer, a thickening agent and a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic or non-ionic type.
  • Cosmetics such as emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or any other ingredients commonly used in cosmetics. It may contain adjuvants commonly used in the field.
  • the composition of the present invention may be a food composition, for example, a health functional food.
  • a health functional food means a food manufactured and processed using raw materials or ingredients useful for the human body
  • functionality means a health purpose such as regulating nutrients or physiological action with respect to the structure and function of the human body. It means to consume for the purpose of obtaining useful effects.
  • the formulation of the food composition is not particularly limited, but, for example, may be formulated as tablets, granules, powders, liquids such as drinks, caramel, gels, bars, and the like.
  • the food composition of each dosage form can be formulated by a person skilled in the art without difficulty according to the dosage form or purpose of use, which is commonly used in the field.
  • the pharmaceutical composition of the present invention may be administered parenterally or orally according to a desired method, and the dosage may vary depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate and severity of disease, etc. Its scope is diverse.
  • the therapeutically effective amount of the composition may vary depending on the method of administration, the target site, and the condition of the patient.
  • the compound of the present invention can be prepared by a preparation method as shown in Schemes 1 to 3 below.
  • DMEM Dulbecco's modified eagle's medium
  • FBS fetal bovine serum
  • penicillin/streptomycin 100U/ml
  • B16 melanoma cells 200 ⁇ L of B16 melanoma cells were dispensed in a 96-well plate to 3 X 10 3 cells/well, and then cultured at 37° C., 5% CO 2 in an incubator for 24 hours.
  • B16 melanoma cells were treated with compounds of 0, 1, 3, 10, and 30 ⁇ M, respectively, for 2 hours, and stimulated with ⁇ -MSH (melanocyte-stimulating hormone) (100 nM) for 72 hours.
  • ⁇ -MSH melanocyte-stimulating hormone
  • the amount of melanin in the negative control group that was not treated with anything was set to 1, and the melanin amount of the positive control ( ⁇ -MSH only) and experimental group ( ⁇ -MSH, and compound treated group) was calculated as a ratio to the melanin amount of the negative control group. .
  • the compounds of Examples 1 and 2 exhibited an effect of reducing the amount of melanin when the concentration was 10 ⁇ M, and even more excellent compared to the compound of Comparative Example 3 (Arbutin) It showed a reduction effect.
  • the dimer compound (Examples 1 and 2) of the present invention has a superior melanogenesis inhibition and melanosome degradation effect compared to monomeric compounds (Comparative Examples 1 and 2) and arbutin (Comparative Example 3). Confirmed. From this, it can be seen that the compounds of the present invention exhibit excellent inhibitory effects on the melanin biosynthesis signaling pathway induced by ⁇ -MSH.
  • B16 melanoma cells 200 ⁇ L of B16 melanoma cells were dispensed in a 96-well plate to 3 X 10 3 cells/well, and then cultured at 37° C., 5% CO 2 in an incubator for 24 hours. B16 melanoma cells were treated with the compound under the same conditions as in Example 2 for 2 hours.
  • ⁇ -MSH was treated at a concentration of 100 nM for 76 hours, the medium was removed, and the results of measuring absorbance at 550 nm using MTT assay are shown in FIGS. 5 to 10 .

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition de blanchiment de la peau contenant un dérivé de dihydrofuran-2(3h)-one ayant une activité inhibitrice de la mélanogenèse et une activité de dégradation de mélanosome, un isomère correspondant ou un sel pharmaceutiquement acceptable de celui-ci. En particulier, la composition de la présente invention inhibe la mélanogenèse et favorise la dégradation des mélanosomes par l'action d'un dérivé de dihydrofuran-2(3h)-one dans une voie de signalisation de la biosynthèse de la mélanine induite par l'hormone de stimulation des mélanocytes (α-MSH).
PCT/KR2021/013839 2020-10-12 2021-10-08 Composition de blanchiment de la peau contenant un dimère dihydrofuran-2(3h)-one WO2022080765A1 (fr)

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KR1020200131466A KR20220048378A (ko) 2020-10-12 2020-10-12 디하이드로퓨란-2(3h)-온 이량체를 포함하는 피부미백용 조성물
KR10-2020-0131466 2020-10-12

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