WO2022092639A1 - Stabilization composition including hydroquinone or derivative thereof - Google Patents
Stabilization composition including hydroquinone or derivative thereof Download PDFInfo
- Publication number
- WO2022092639A1 WO2022092639A1 PCT/KR2021/014281 KR2021014281W WO2022092639A1 WO 2022092639 A1 WO2022092639 A1 WO 2022092639A1 KR 2021014281 W KR2021014281 W KR 2021014281W WO 2022092639 A1 WO2022092639 A1 WO 2022092639A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- hydroquinone
- composition
- mixture
- derivative
- Prior art date
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- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 title claims abstract description 184
- 239000000203 mixture Substances 0.000 title claims abstract description 97
- 230000006641 stabilisation Effects 0.000 title description 2
- 238000011105 stabilization Methods 0.000 title description 2
- 239000011787 zinc oxide Substances 0.000 claims abstract description 36
- 235000014692 zinc oxide Nutrition 0.000 claims abstract description 36
- 229910044991 metal oxide Inorganic materials 0.000 claims abstract description 30
- 150000004706 metal oxides Chemical class 0.000 claims abstract description 30
- 229940105847 calamine Drugs 0.000 claims abstract description 28
- 229910052864 hemimorphite Inorganic materials 0.000 claims abstract description 28
- CPYIZQLXMGRKSW-UHFFFAOYSA-N zinc;iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+3].[Fe+3].[Zn+2] CPYIZQLXMGRKSW-UHFFFAOYSA-N 0.000 claims abstract description 28
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims abstract description 25
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims abstract description 19
- 229940001584 sodium metabisulfite Drugs 0.000 claims abstract description 19
- 235000010262 sodium metabisulphite Nutrition 0.000 claims abstract description 19
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims abstract description 14
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims abstract description 14
- 239000004480 active ingredient Substances 0.000 claims abstract description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 16
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 12
- 150000003628 tricarboxylic acids Chemical class 0.000 claims description 11
- 235000015165 citric acid Nutrition 0.000 claims description 10
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
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- 239000001361 adipic acid Substances 0.000 claims description 6
- 235000011037 adipic acid Nutrition 0.000 claims description 6
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 claims description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 5
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 claims description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- FMWSHZRIJXQMOO-UHFFFAOYSA-N Glutinic acid Natural products OC(=O)C=C(C)CCC1(C)C(C)CCC2(C)C1CCC=C2C(O)=O FMWSHZRIJXQMOO-UHFFFAOYSA-N 0.000 claims description 4
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 4
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 4
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 claims description 4
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- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 3
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 claims description 3
- LKVFCSWBKOVHAH-UHFFFAOYSA-N 4-Ethoxyphenol Chemical compound CCOC1=CC=C(O)C=C1 LKVFCSWBKOVHAH-UHFFFAOYSA-N 0.000 claims description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 3
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- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical group C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 claims description 3
- 229960000990 monobenzone Drugs 0.000 claims description 3
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 claims description 3
- XVOUMQNXTGKGMA-OWOJBTEDSA-N (E)-glutaconic acid Chemical compound OC(=O)C\C=C\C(O)=O XVOUMQNXTGKGMA-OWOJBTEDSA-N 0.000 claims description 2
- 239000001124 (E)-prop-1-ene-1,2,3-tricarboxylic acid Substances 0.000 claims description 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 claims description 2
- JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 claims description 2
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 claims description 2
- GFBCWCDNXDKFRH-UHFFFAOYSA-N 4-(oxan-2-yloxy)phenol Chemical compound C1=CC(O)=CC=C1OC1OCCCC1 GFBCWCDNXDKFRH-UHFFFAOYSA-N 0.000 claims description 2
- HJRGXHLPICBGPA-UHFFFAOYSA-N 4-(thian-2-yloxy)phenol Chemical compound C1=CC(O)=CC=C1OC1SCCCC1 HJRGXHLPICBGPA-UHFFFAOYSA-N 0.000 claims description 2
- ODBLHEXUDAPZAU-ZAFYKAAXSA-N D-threo-isocitric acid Chemical compound OC(=O)[C@H](O)[C@@H](C(O)=O)CC(O)=O ODBLHEXUDAPZAU-ZAFYKAAXSA-N 0.000 claims description 2
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- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 2
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- 229940040563 agaric acid Drugs 0.000 claims description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims description 2
- GTZCVFVGUGFEME-IWQZZHSRSA-N cis-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C\C(O)=O GTZCVFVGUGFEME-IWQZZHSRSA-N 0.000 claims description 2
- HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 claims description 2
- 229940018557 citraconic acid Drugs 0.000 claims description 2
- 229930182478 glucoside Natural products 0.000 claims description 2
- -1 hydroquinone glucoside Chemical class 0.000 claims description 2
- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 claims description 2
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- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
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- HMFHBZSHGGEWLO-FCAWWPLPSA-N beta-L-ribose Chemical compound OC[C@@H]1O[C@H](O)[C@@H](O)[C@H]1O HMFHBZSHGGEWLO-FCAWWPLPSA-N 0.000 description 1
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- 238000006243 chemical reaction Methods 0.000 description 1
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- BOAMTGHGHLIYHH-UHFFFAOYSA-N cyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C=C1.O=C1C=CC(=O)C=C1 BOAMTGHGHLIYHH-UHFFFAOYSA-N 0.000 description 1
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- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 1
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- 210000002752 melanocyte Anatomy 0.000 description 1
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- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
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- 230000002588 toxic effect Effects 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
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Definitions
- the present disclosure relates to a composition containing hydroquinone or a derivative thereof useful for skin whitening, etc. while reducing skin irritation, and at the same time securing the stability of hydroquinone or a derivative thereof.
- a method of inhibiting melanin production by inhibiting some of the melanin production process is used.
- a whitening agent ascorbic acid, arbutin, kojic acid, etc. have been used in cosmetics, but the whitening effect is not high.
- Hydroquinone or a derivative thereof has an excellent whitening effect than the above whitening ingredients.
- hydroquinone or a derivative thereof is easily discolored by being oxidized by air, heat, and/or light, and may be toxic to melanocytes upon oxidation.
- oxidized hydroquinone produces quinhydrone through benzoquinone (p-benzoquinone), which is known to induce cytotoxicity and to have carcinogenic and allergenic properties. Due to this instability, only limited concentrations of hydroquinone are permitted in each country.
- the problem to be solved by the present disclosure is to provide a composition containing hydroquinone or a derivative thereof, in which skin irritation is reduced and stability is secured.
- the present disclosure contains hydroquinone or a derivative thereof as an active ingredient, and a metal oxide (preferably zinc oxide (ZnO), calamine, titanium dioxide (TiO 2 ), or their
- a metal oxide preferably zinc oxide (ZnO), calamine, titanium dioxide (TiO 2 ), or their
- the composition further comprising a mixture, more preferably zinc oxide, calamine or a mixture thereof, (i) sodium metabisulfite, sodium hydrogen sulfite to improve the stability of hydroquinone or a derivative thereof bisulfite) or a mixture thereof, and (ii) bi-carboxylic acid, tri-carboxylic acid, or a mixture thereof, to provide a composition containing hydroquinone or a derivative thereof.
- the composition is a cosmetic or pharmaceutical composition.
- the present disclosure contains hydroquinone or a derivative thereof as an active ingredient, and a metal oxide (preferably zinc oxide (ZnO), calamine, titanium dioxide (TiO 2 ), or a mixture thereof, more preferably In the composition further comprising zinc oxide, calamine or mixtures thereof, (i) sodium metabisulfite (Sodium metabisulfite), sodium bisulfite (Sodium bisulfite) or mixtures thereof, and (ii) bi-carboxylic It provides a method for improving the stability of hydroquinone or a derivative thereof, characterized in that it contains two components of acid, tri-carboxylic acid, or a mixture thereof.
- hydroquinone or a derivative thereof used for skin whitening, etc. has skin irritation, and such skin irritation is zinc oxide (ZnO), calamine (Calamine, a mixture of zinc oxide and iron oxide), titanium dioxide ( It can be reduced by adding a metal oxide such as TIO 2 ) or a mixture thereof, but when hydroquinone and metal oxide are included at the same time, the metal oxide component further accelerates the oxidation of hydroquinone. did This problem was not easy to solve even using various known means.
- the present inventors have completed the present invention by confirming that by using the additives of (i) and (ii) in combination, it is possible to achieve high stability while very low skin irritation of hydroquinone or a derivative thereof.
- the cosmetic or pharmaceutical composition of the present invention contains hydroquinone or a derivative thereof as a whitening active ingredient.
- the cosmetic or pharmaceutical composition of the present invention contains hydroquinone as a whitening active ingredient.
- the hydroquinone derivatives include arbutin, 4-hydroxyanisole, hydroquinone monobenzyl ether, hydroquinone monomethyl ether, hydroquinone monoethyl ether, t-butyl hydroquinone, 4 -[(tetrahydro-2H-pyran-2-yl)oxy]phenol, 4-[(tetrahydro-2H-thiopyran-2-yl)oxy]phenol, hydroquinone glucoside derivatives (e.g.
- hydroquinone ⁇ - D-glucose hydroquinone ⁇ -D-glucose, hydroquinone ⁇ -D-glucose, hydroquinone ⁇ -L-glucose, hydroquinone ⁇ -L-glucose, hydroquinone ⁇ -D-galactose, hydroquinone ⁇ -D-galactose, hydroquinone ⁇ -L-galactose, hydroquinone ⁇ -L -galactose, hydroquinone ⁇ -D-ribose, hydroquinone ⁇ -D-ribose, hydroquinone ⁇ -L-ribose, hydroquinone ⁇ -L-ribose, hydroquinone ⁇ -D-arabinose, hydroquinone ⁇ -D-arabinose, hydroquinone ⁇ -L- arabinose, hydroquinone ⁇ -L-arabinose, hydroquinone ⁇ -D-glucosamine, hydroquino
- Such hydroquinone or a derivative thereof may be contained in an amount of 0.1 to 10% by weight based on the total weight of the composition, and is preferably contained in an amount of 0.5 to 10% by weight. When contained in an amount of 10% by weight or more, there may be concerns about irritation to the skin.
- the composition of the present invention includes a metal oxide for reducing skin irritation, and the metal oxide includes one or a mixture of two or more selected from the group consisting of zinc oxide, calamine, titanium dioxide, iron oxide, aluminum oxide, and the like.
- the metal oxide is zinc oxide, titanium dioxide, calamine, or a mixture thereof.
- the metal oxide is zinc oxide, calamine, or a mixture thereof.
- the total content of the metal oxide used for reducing skin irritation in the composition of the present disclosure may be contained in an amount of 0.1 to 20% by weight based on the total weight of the composition, and is preferably contained in an amount of 1 to 15% by weight.
- the bi-carboxylic acid or tri-carboxylic acid malic acid, succinic acid, tartaric acid, maleic acid, fumaric acid, citric acid acid), adipic acid, oxalic acid, malonic acid, glutaric acid, glutaconic acid, sebacic acid, azelaic acid ( azelaic acid, pimelic acid, isocitric acid, aconitic acid, agaric acid, itaconic acid, citraconic acid, Muconic acid (muconic acid), glutinic acid (glutinic acid) or a mixture thereof may be used.
- the bi-carboxylic acid or tri-carboxylic acid is citric acid, succinic acid, adipic acid, tartaric acid, or a mixture thereof.
- the composition of the present disclosure comprises (i) sodium metabisulfite, and (ii) citric acid, succinic acid, adipic acid, tartaric acid, or a mixture thereof as components (i) and (ii), respectively.
- the composition of the present invention includes both components (i) and (ii) for stabilization of hydroquinone or a derivative thereof, and preferably, the mixing ratio of components (i) and (ii) is 3 :7 - 7:3 weight ratio range.
- the total content of components (i) and (ii) is preferably 0.1% by weight or more, preferably 0.1 to 10% by weight, and more preferably 0.1 to 5% by weight, based on the total weight of the composition. and 0.2 to 5% by weight is still more preferred.
- the total content of components (i) and (ii) is preferably 0.1% by weight or more, preferably 0.1 to 10% by weight, and more preferably 0.1 to 5% by weight, based on the total weight of the composition. and 0.2 to 5% by weight is still more preferred.
- the total content of components (i) and (ii) in the composition of the present invention is 0.1 to 10% by weight based on the total weight of the composition, and the mixing ratio of components (i) and (ii) is 3: 7 - 7:3 weight ratio.
- both components (i) and (ii) are essential, and preferably, when the two species are mixed with each other and the mixed weight ratio is used in a ratio of 7:3 to 3:7, the effect of preventing discoloration of hydroquinone or a derivative thereof is reduced. become more excellent
- hydroquinone or a derivative thereof 0.1 to 10% by weight; 1 to 15% by weight of zinc oxide (ZnO), calamine, or a mixture thereof; and the remaining amount of a solvent, comprising (i) sodium metabisulfite, sodium bisulfite, or a mixture thereof, and (ii) bi-carboxylic acid, tri-carboxylic acid, or a mixture thereof.
- a solvent comprising (i) sodium metabisulfite, sodium bisulfite, or a mixture thereof, and (ii) bi-carboxylic acid, tri-carboxylic acid, or a mixture thereof.
- the cosmetic or pharmaceutical composition according to the present disclosure may include various additives for a cosmetic or pharmaceutical composition within a range that does not impair the purpose of the present invention.
- other additives include the hydroquinone or derivatives thereof; metal oxides (preferably zinc oxide (ZnO), calamine, titanium dioxide (TIO 2 ) or mixtures thereof, more preferably zinc oxide, calamine or mixtures thereof); (i) a component; and (ii) excluding components.
- the cosmetic composition according to the present disclosure may contain a residual amount of a solvent in addition to the above-mentioned ingredients. That is, as a substance for dissolving hydroquinone or a derivative thereof, water, a hydrophilic solvent, or a mixture thereof is selected from the group consisting of hydroquinone or a derivative thereof; Zinc oxide (ZnO), calamine (Calamine), titanium dioxide (TIO 2 ), such as metal oxides or mixtures thereof; (i) a component; and (ii) a weight excluding components.
- a hydrophilic solvent a polyhydric alcohol or a volatile organic solvent may be used without limitation.
- hydrophilic solvent may be used in an amount of 5 to 80% by weight based on the total weight of the composition.
- a hydrophilic solvent is not limited in the present invention, when used, it may help the stability of hydroquinone or a derivative thereof.
- the cosmetic or pharmaceutical composition according to the present disclosure may be prepared according to a conventional manufacturing method used in the art.
- the composition of the present disclosure may be formulated in the form of a skin, serum, gel, lotion, cream, powder, patch, etc. and applied in various ways, and when applied to the skin, it may provide the efficacy of a whitening effect.
- composition for cosmetic, pharmaceutical or personal care according to the present invention contains the ingredients according to the present invention within the content limit allowed by the relevant laws and regulations of each country.
- the present disclosure provides a composition containing hydroquinone or a derivative thereof in which skin irritation is improved and stability is secured.
- the composition according to the present disclosure increases storage stability by preventing the accelerated oxidation reaction of hydroquinone or a derivative thereof by external environmental factors such as heat, oxygen, light, etc. and zinc oxide, and reduces toxicity and inflammation by preventing discoloration reaction can be reduced.
- the composition of the present disclosure can improve storage stability, biocompatibility, skin whitening effect, and the like, and thus can be widely applied as cosmetics and pharmaceuticals for improving whitening.
- 1 is a result of evaluating whether or not discoloration according to the mixing ratio of two types of antioxidants used to increase storage stability in a formulation containing hydroquinone and calamine, a metal oxide.
- Examples 1 to 5 and Comparative Examples 1 to 6 were prepared and evaluated according to the composition shown in Table 1 below.
- hydrophilic solvents and antioxidants 1 and 2 were mixed at room temperature. While stirring at 3000 rpm using a homomixer, calamine, a metal oxide, was added and dispersed. When the calamine was sufficiently homogeneously dispersed by stirring for 15 minutes, hydroquinone was added and the mixture was completely dissolved by stirring at 3000 rpm for 5 minutes.
- the degree of discoloration was measured as follows. In order to check the storage stability of the Table 1 composition, it was stored at 50° C. for 4 weeks. After that, the supernatant, in which the metal oxide was precipitated, was transferred to a 96-well opaque white plate by 200ul. Thereafter, L value (lightness), a value (redness), and b value (yellowness) were measured three times with a Chromameter CR-400 (Minolta, Japan). overall color change It is expressed as a value.
- both antioxidants are essential, preferably, when the two antioxidants are mixed in a specific ratio and used, the storage stability of hydroquinone in a composite composition of metal oxide and hydroquinone can be improved.
- Examples 6 to 7 and Comparative Examples 7 to 10 were prepared and evaluated according to the composition shown in Table 2 below.
- the manufacturing method and the method of measuring the degree of discoloration were the same as those of Examples 1 to 5 above.
- Examples 6, 8, 9 and Comparative Examples 11 to 15 were prepared and evaluated according to the composition shown in Table 3 below.
- the manufacturing method and the method of measuring the degree of discoloration were the same as those of Examples 1 to 5 above.
- Examples 3, 10, and 11 were prepared and evaluated according to the composition shown in Table 4 below.
- the manufacturing method and the method of measuring the degree of discoloration were the same as those of Examples 1 to 5 above.
- Example 11 active ingredient hydroquinone 4 4 4 metal oxide calamine 8 8 8 hydrophilic solvent dipropylene glycol 10 10 10 hydrophilic solvent ethanol to 100 to 100 to 100 antioxidant 1 Citric acid 0.15 0.1 0.05 antioxidant 2 Sodium metabisulfite 0.15 0.1 0.05 Discoloration ⁇ E 1.8 2.1 6.1
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Abstract
The present disclosure relates to a composition including hydroquinone or a derivative thereof as an active ingredient for skin whitening and additionally a metal oxide (preferably zinc oxide (ZnO), calamine, titanium dioxide (TIO2), or a mixture thereof) as an ingredient for alleviating skin irritation, wherein the stability of the hydroquinone or the derivative thereof is secured. To secure such stability, the composition of the present disclosure includes (i) sodium metabisulfite, sodium bisulfite, or a mixture thereof, and (ii) bi-carboxylic acid, tri-carboxylic acid, or a mixture thereof.
Description
본 출원은 2020년 10월 29일에 출원된 한국특허출원 제10-2020-0142222호 및 2021년 08월 27일에 출원된 한국특허출원 제10-2021-0114285호에 기초한 우선권을 주장하며, 해당 출원들의 명세서 및 도면에 개시된 모든 내용은 본 출원에 원용된다.This application claims priority based on Korean Patent Application No. 10-2020-0142222, filed on October 29, 2020 and Korean Patent Application No. 10-2021-0114285, filed on August 27, 2021, All contents disclosed in the specification and drawings of the applications are incorporated herein by reference.
본 개시는 피부 미백 등에 유용한 히드로퀴논 또는 이의 유도체를 함유하면서도 피부 자극이 줄어들었을 뿐만 아니라, 동시에 히드로퀴논 또는 이의 유도체의 안정성이 확보된 조성물에 관한 것이다.The present disclosure relates to a composition containing hydroquinone or a derivative thereof useful for skin whitening, etc. while reducing skin irritation, and at the same time securing the stability of hydroquinone or a derivative thereof.
피부 색소 침착을 방지하기 위해서는 멜라닌 생성 과정 중 일부 과정을 저해하여 멜라닌 생성을 억제하는 방법이 이용된다. 이러한 미백제로는 화장품에 아스코르브산, 알부틴, 코지산 등이 이용되어 왔으나, 미백 효과는 높지 않다. In order to prevent skin pigmentation, a method of inhibiting melanin production by inhibiting some of the melanin production process is used. As such a whitening agent, ascorbic acid, arbutin, kojic acid, etc. have been used in cosmetics, but the whitening effect is not high.
히드로퀴논(hydroquinone) 또는 이의 유도체는 상기 미백 성분들보다 미백 효과가 탁월하다. 그러나, 히드로퀴논 또는 이의 유도체는 공기, 열, 및/또는 빛에 의해 산화되어 쉽게 변색되며, 산화 시 멜라닌 생성 세포에 대한 독성이 있을 수 있다. 구체적으로, 산화된 하이드로퀴논은 벤조퀴논(p-benzoquinone)을 거쳐 퀸하이드론(Quinhydrone)을 생성하는데, 이들은 세포 독성을 유발하고, 발암 및 알러지 유발 특성을 가진다고 알려져 있다. 이러한 불안정성으로 히드로퀴논은 각 나라별로 제한적인 농도만 허가되고 있다.Hydroquinone or a derivative thereof has an excellent whitening effect than the above whitening ingredients. However, hydroquinone or a derivative thereof is easily discolored by being oxidized by air, heat, and/or light, and may be toxic to melanocytes upon oxidation. Specifically, oxidized hydroquinone produces quinhydrone through benzoquinone (p-benzoquinone), which is known to induce cytotoxicity and to have carcinogenic and allergenic properties. Due to this instability, only limited concentrations of hydroquinone are permitted in each country.
히드로퀴논의 산화 등을 방지하기 위해 pH를 4 근처로 조절하거나, 다양한 항산화제를 적용하는 방법이 보고되어 있다. 그러나 종래의 방법은 항산화제 자체의 변색이 발생되거나 히드로퀴논으로부터 유래한 자극 우려가 여전히 존재한다. 이러한 자극은 오히려 염증 후 과색소침착 (post-inflammatory hyperpigmentation) 등의 부작용을 일으킬 수 있다.In order to prevent the oxidation of hydroquinone, it has been reported that the pH is adjusted to around 4 or a method of applying various antioxidants. However, in the conventional method, discoloration of the antioxidant itself or irritation from hydroquinone still exists. Rather, such stimulation may cause side effects such as post-inflammatory hyperpigmentation.
이러한 히드로퀴논의 어느 한 가지 단점을 극복해 볼 수는 있으나, 상기 2가지 단점인 히드로퀴논의 자극성 및 불안정성 동시에 만족하기는 어렵다.Although any one of the disadvantages of hydroquinone can be overcome, it is difficult to simultaneously satisfy the above two disadvantages, the irritation and instability of hydroquinone.
따라서 본 개시가 해결하고자 하는 과제는 피부 자극이 줄어들면서도 안정성(stability)이 확보된, 히드로퀴논 또는 이의 유도체 함유 조성물을 제공하는 것이다.Accordingly, the problem to be solved by the present disclosure is to provide a composition containing hydroquinone or a derivative thereof, in which skin irritation is reduced and stability is secured.
상기 과제를 해결하기 위하여, 본 개시는 유효 성분으로 히드로퀴논 또는 이의 유도체를 함유하고, 금속 산화물(바람직하게는, 산화아연(ZnO), 칼라민(Calamine), 이산화 티타늄(TiO2), 또는 이들의 혼합물, 더욱 바람직하게는 산화아연, 칼라민 또는 이들의 혼합물)을 추가로 포함하는 조성물에 있어서, 히드로퀴논 또는 이의 유도체의 안정성 개선을 위해 (i) 메타중아황산나트륨(Sodium metabisulfite), 아황산수소나트륨(Sodium bisulfite) 또는 이들의 혼합물, 및 (ii) bi-carboxylic acid, tri-carboxylic acid, 또는 이들의 혼합물을 포함하는 것을 특징으로 하는, 히드로퀴논 또는 이의 유도체 함유 조성물을 제공한다. 본 개시에 있어, 바람직하게는, 조성물은 화장료 또는 약학 조성물이다. In order to solve the above problems, the present disclosure contains hydroquinone or a derivative thereof as an active ingredient, and a metal oxide (preferably zinc oxide (ZnO), calamine, titanium dioxide (TiO 2 ), or their In the composition further comprising a mixture, more preferably zinc oxide, calamine or a mixture thereof, (i) sodium metabisulfite, sodium hydrogen sulfite to improve the stability of hydroquinone or a derivative thereof bisulfite) or a mixture thereof, and (ii) bi-carboxylic acid, tri-carboxylic acid, or a mixture thereof, to provide a composition containing hydroquinone or a derivative thereof. In the present disclosure, preferably, the composition is a cosmetic or pharmaceutical composition.
즉, 본 개시는 유효 성분으로 히드로퀴논 또는 이의 유도체를 함유하고, 금속 산화물(바람직하게는, 산화아연(ZnO), 칼라민(Calamine), 이산화 티타늄(TiO2), 또는 이들의 혼합물, 더욱 바람직하게는 산화아연, 칼라민 또는 이들의 혼합물)을 추가로 포함하는 조성물에 있어서, (i) 메타중아황산나트륨(Sodium metabisulfite), 아황산수소나트륨(Sodium bisulfite) 또는 이들의 혼합물, 및 (ii) bi-carboxylic acid, tri-carboxylic acid, 또는 이들의 혼합물의 2가지 성분을 포함시키는 것을 특징으로 하는, 히드로퀴논 또는 이의 유도체의 안정성을 개선하는 방법을 제공한다. That is, the present disclosure contains hydroquinone or a derivative thereof as an active ingredient, and a metal oxide (preferably zinc oxide (ZnO), calamine, titanium dioxide (TiO 2 ), or a mixture thereof, more preferably In the composition further comprising zinc oxide, calamine or mixtures thereof, (i) sodium metabisulfite (Sodium metabisulfite), sodium bisulfite (Sodium bisulfite) or mixtures thereof, and (ii) bi-carboxylic It provides a method for improving the stability of hydroquinone or a derivative thereof, characterized in that it contains two components of acid, tri-carboxylic acid, or a mixture thereof.
본 발명자들은, 피부 미백 등의 용도로 사용되는 히드로퀴논(Hydroquinone) 또는 이의 유도체는 피부 자극이 있는데, 이러한 피부 자극이 산화아연(ZnO), 칼라민(Calamine, 산화아연 및 산화철 혼합물), 티타늄다이옥사이드(TIO2) 등의 금속 산화물 또는 이들의 혼합물을 첨가하여 줄어들 수 있으나, 히드로퀴논과 금속산화물을 동시에 포함할 경우, 금속산화물 성분이 히드로퀴논의 산화를 더욱 가속화시켜 오히려 히드로퀴논이 산화 갈변하는 문제가 있음을 확인하였다. 이러한 문제는 알려진 여러 수단을 이용하여도 해결이 쉽지 않았다. 본 발명자들은, 상기 (i) 및 (ii)의 첨가제를 조합하여 사용함으로써 히드로퀴논 또는 이의 유도체의 피부 자극은 매우 낮추면서도 높은 안정성을 달성할 수 있음을 확인하여 본 발명을 완성하였다. According to the present inventors, hydroquinone or a derivative thereof used for skin whitening, etc. has skin irritation, and such skin irritation is zinc oxide (ZnO), calamine (Calamine, a mixture of zinc oxide and iron oxide), titanium dioxide ( It can be reduced by adding a metal oxide such as TIO 2 ) or a mixture thereof, but when hydroquinone and metal oxide are included at the same time, the metal oxide component further accelerates the oxidation of hydroquinone. did This problem was not easy to solve even using various known means. The present inventors have completed the present invention by confirming that by using the additives of (i) and (ii) in combination, it is possible to achieve high stability while very low skin irritation of hydroquinone or a derivative thereof.
본 개시에 있어, 본 발명의 화장료 또는 약학 조성물은 미백 유효 성분으로 히드로퀴논 또는 이의 유도체를 함유한다. 바람직하게, 본 발명의 화장료 또는 약학 조성물은 미백 유효 성분으로 히드로퀴논을 함유한다.In the present disclosure, the cosmetic or pharmaceutical composition of the present invention contains hydroquinone or a derivative thereof as a whitening active ingredient. Preferably, the cosmetic or pharmaceutical composition of the present invention contains hydroquinone as a whitening active ingredient.
본 개시에 있어, 상기 히드로퀴논의 유도체로는 아르부틴(arbutin), 4-하이드록시아니솔(4-hydroxyanisole), 히드로퀴논 모노벤질 에테르, 히드로퀴논 모노메틸 에테르, 히드로퀴논 모노에틸 에테르, t-부틸 히드로퀴논, 4-[(테트라하이드로-2H-피란-2-일)옥시]페놀, 4-[(테트라하이드로-2H-티오피란-2-일)옥시]페놀, 히드로퀴논 글루코사이드 유도체들 (예를 들어, hydroquinone α-D-glucose, hydroquinone β-D-glucose, hydroquinone α-L-glucose, hydroquinone β-L-glucose, hydroquinone α-D-galactose, hydroquinone β-D-galactose, hydroquinone α-L-galactose, hydroquinone β-L-galactose, hydroquinone α-D-ribose, hydroquinone β-D-ribose, hydroquinone α-L-ribose, hydroquinone β-L-ribose, hydroquinone α-D-arabinose, hydroquinone β-D-arabinose, hydroquinone α-L-arabinose, hydroquinone β-L-arabinose, hydroquinone α-D-glucosamine, hydroquinone β-D-glucosamine, hydroquinone α-L-glucosamine, hydroquinone β-L-glucosamine, hydroquinone α-D-galactosamine, hydroquinone β-D-galactosamine, hydroquinone α-L-galactosamine, hydroquinione β-L-galactosamine, hydroquinone α-D-glucuronic acid, hydroquinone β-D-glucuronic acid, hydroquinone α-L-glucuronic acid, hydroquinone β-L-glucuronic acid, hydroquinone α-D-galacturonic acid, hydroquinone β-D-galacturonic acid, hydroquinone α-L-galacturonic acid, 및 hydroquinone β-L-galacturonic acid) 등이 이용될 수 있다. 본 발명의 바람직한 일 양태에 있어, 상기 히드로퀴논의 유도체는 히드로퀴논 모노벤질 에테르, 히드로퀴논 모노메틸 에테르 및 히드로퀴논 모노에틸 에테르로 이루어지는 군에서 선택되는 1종 이상이다.In the present disclosure, the hydroquinone derivatives include arbutin, 4-hydroxyanisole, hydroquinone monobenzyl ether, hydroquinone monomethyl ether, hydroquinone monoethyl ether, t-butyl hydroquinone, 4 -[(tetrahydro-2H-pyran-2-yl)oxy]phenol, 4-[(tetrahydro-2H-thiopyran-2-yl)oxy]phenol, hydroquinone glucoside derivatives (e.g. hydroquinone α- D-glucose, hydroquinone β-D-glucose, hydroquinone α-L-glucose, hydroquinone β-L-glucose, hydroquinone α-D-galactose, hydroquinone β-D-galactose, hydroquinone α-L-galactose, hydroquinone β-L -galactose, hydroquinone α-D-ribose, hydroquinone β-D-ribose, hydroquinone α-L-ribose, hydroquinone β-L-ribose, hydroquinone α-D-arabinose, hydroquinone β-D-arabinose, hydroquinone α-L- arabinose, hydroquinone β-L-arabinose, hydroquinone α-D-glucosamine, hydroquinone β-D-glucosamine, hydroquinone α-L-glucosamine, hydroquinone β-L-glucosamine, hydroquinone α-D-galactosamine, hydroquinone β-D-galactosamine , hydroquinone α-L-galactosamine, hydroquinione β-L-galactosamine, hydroquinone α-D-glucuronic acid, hydroquinone β-D-glucuronic acid, hydroquinone α-L-glucuronic acid, hydr oquinone β-L-glucuronic acid, hydroquinone α-D-galacturonic acid, hydroquinone β-D-galacturonic acid, hydroquinone α-L-galacturonic acid, and hydroquinone β-L-galacturonic acid) may be used. In a preferred aspect of the present invention, the hydroquinone derivative is at least one selected from the group consisting of hydroquinone monobenzyl ether, hydroquinone monomethyl ether and hydroquinone monoethyl ether.
이러한 히드로퀴논 또는 이의 유도체는 조성물 총 중량에 대해 0.1~10 중량%의 양으로 함유될 수 있으며, 0.5~10 중량%의 양으로 함유되는 것이 바람직하다. 10 중량% 이상의 양으로 함유될 경우 피부에 대한 자극 우려가 있을 수 있으며, 이 경우 오히려 자극에 의한 염증이 발생하고 이후 과색소침착과 같은 부작용이 유발될 우려가 있다.Such hydroquinone or a derivative thereof may be contained in an amount of 0.1 to 10% by weight based on the total weight of the composition, and is preferably contained in an amount of 0.5 to 10% by weight. When contained in an amount of 10% by weight or more, there may be concerns about irritation to the skin.
본 발명의 조성물은 피부 자극 감소를 위한 금속 산화물을 포함하며, 이러한 금속 산화물로는 산화아연, 칼라민, 이산화 티타늄, 산화 철, 산화 알루미늄 등으로 이루어진 군에서 선택되는 1종 또는 2종 이상의 혼합물을 사용할 수 있다. 본 발명의 일 양태에 있어, 상기 금속 산화물은 산화아연, 이산화 티타늄, 칼라민, 또는 이들의 혼합물이다. 본 발명의 바람직한 일 양태에 있어, 상기 금속 산화물은 산화아연, 칼라민, 또는 이들의 혼합물이다.The composition of the present invention includes a metal oxide for reducing skin irritation, and the metal oxide includes one or a mixture of two or more selected from the group consisting of zinc oxide, calamine, titanium dioxide, iron oxide, aluminum oxide, and the like. can be used In one aspect of the present invention, the metal oxide is zinc oxide, titanium dioxide, calamine, or a mixture thereof. In a preferred embodiment of the present invention, the metal oxide is zinc oxide, calamine, or a mixture thereof.
본 개시의 조성물에 있어 피부 자극 감소를 위해 사용되는 금속 산화물의 총 함량은 조성물 총 중량에 대해 0.1~20 중량%로 함유될 수 있으며, 1~15 중량%로 함유되는 것이 바람직하다. The total content of the metal oxide used for reducing skin irritation in the composition of the present disclosure may be contained in an amount of 0.1 to 20% by weight based on the total weight of the composition, and is preferably contained in an amount of 1 to 15% by weight.
본 개시에 있어, 상기 bi-carboxylic acid 또는 tri-carboxylic acid로는 사과산(malic acid), 숙신산(succinic acid), 주석산(tartaric acid), 말레산(maleic acid), 푸마르산(fumaric acid), 구연산(citric acid), 아디프산(adipic acid), 옥살산(oxalic acid), 말론산(malonic acid), 글루타르산 (glutaric acid), 글루타콘산(glutaconic acid), 세바스산 (sebacic acid), 아젤라인산 (azelaic acid), 피멜산 (pimelic acid), 아이소시트르산 (isocitric acid), 아코니트산 (aconitic acid), 아가르산(agaric acid), 이타콘산 (itaconic acid), 시트라코닉산 (citraconic acid), 뮤콘산 (muconic acid), 글루티닉산(glutinic acid) 또는 이들의 혼합물이 사용될 수 있다. 본 발명의 바람직한 일 양태에 있어, 상기 bi-carboxylic acid 또는 tri-carboxylic acid은 구연산, 숙신산, 아디프산, 주석산 또는 이들의 혼합물이다. In the present disclosure, as the bi-carboxylic acid or tri-carboxylic acid, malic acid, succinic acid, tartaric acid, maleic acid, fumaric acid, citric acid acid), adipic acid, oxalic acid, malonic acid, glutaric acid, glutaconic acid, sebacic acid, azelaic acid ( azelaic acid, pimelic acid, isocitric acid, aconitic acid, agaric acid, itaconic acid, citraconic acid, Muconic acid (muconic acid), glutinic acid (glutinic acid) or a mixture thereof may be used. In a preferred aspect of the present invention, the bi-carboxylic acid or tri-carboxylic acid is citric acid, succinic acid, adipic acid, tartaric acid, or a mixture thereof.
바람직한 일 양태에서, 본 개시의 조성물은 상기 (i) 및 (ii) 성분으로 각각 (i) 메타중아황산나트륨(Sodium metabisulfite), 및 (ii) 구연산, 숙신산, 아디프산, 주석산 또는 이들의 혼합물을 포함한다. In a preferred embodiment, the composition of the present disclosure comprises (i) sodium metabisulfite, and (ii) citric acid, succinic acid, adipic acid, tartaric acid, or a mixture thereof as components (i) and (ii), respectively. include
본 발명에 있어, 본 발명의 조성물은 히드로퀴논 또는 이의 유도체의 안정화를 위해 (i) 및 (ii) 성분 모두를 포함하는 것이 필수적이며, 바람직하게 (i) 성분 및 (ii) 성분의 혼합 비율은 3:7 - 7:3 중량비 범위이다. In the present invention, it is essential that the composition of the present invention includes both components (i) and (ii) for stabilization of hydroquinone or a derivative thereof, and preferably, the mixing ratio of components (i) and (ii) is 3 :7 - 7:3 weight ratio range.
본 발명의 일 태양에 있어, 상기 (i) 및 (ii) 성분의 총 함량은 조성물 총 중량 대비 0.1 중량% 이상이 바람직하고, 0.1 내지 10 중량%가 바람직하며, 0.1 내지 5 중량%가 더욱 바람직하며, 0.2 내지 5 중량%가 더욱 더 바람직하다. 이보다 적은 양으로 함유될 경우 히드로퀴논에 대해 산화 방지 효과를 기대하기 어렵고, 이보다 많이 사용할 경우 안정화제들 자체에 의한 피부 자극이 유발될 우려가 있다.In one aspect of the present invention, the total content of components (i) and (ii) is preferably 0.1% by weight or more, preferably 0.1 to 10% by weight, and more preferably 0.1 to 5% by weight, based on the total weight of the composition. and 0.2 to 5% by weight is still more preferred. When it is contained in an amount smaller than this, it is difficult to expect an antioxidant effect for hydroquinone, and when it is used in an amount higher than this, there is a fear that skin irritation may be caused by the stabilizers themselves.
본 발명의 일 태양에 있어, 본 발명의 조성물 중 (i) 및 (ii) 성분의 총 함량은 조성물 총 중량 대비 0.1 내지 10 중량%이며, (i) 및 (ii) 성분의 혼합 비율은 3:7 - 7:3 중량비이다. In one aspect of the present invention, the total content of components (i) and (ii) in the composition of the present invention is 0.1 to 10% by weight based on the total weight of the composition, and the mixing ratio of components (i) and (ii) is 3: 7 - 7:3 weight ratio.
상기 (i) 및 (ii) 성분의 2가지 안정화제는 단독으로 사용하였을 때는 충분한 안정화 효과를 기대하기 어렵다. 즉, (i) 및 (ii) 성분 모두 필수적이며, 바람직하게는 두 종을 서로 혼합하되 그 혼합 중량비율을 7:3 ~ 3:7의 비율로 사용하는 경우 히드로퀴논 또는 이의 유도체의 변색 방지 효과가 더욱 우수해진다. When the two stabilizers of components (i) and (ii) are used alone, it is difficult to expect a sufficient stabilizing effect. That is, both components (i) and (ii) are essential, and preferably, when the two species are mixed with each other and the mixed weight ratio is used in a ratio of 7:3 to 3:7, the effect of preventing discoloration of hydroquinone or a derivative thereof is reduced. become more excellent
본 발명의 또 다른 태양은, 조성물 총 중량 대비, 히드로퀴논 또는 이의 유도체 0.1 내지 10 중량%; 산화아연(ZnO), 칼라민(Calamine), 또는 이들의 혼합물 1 내지 15 중량%; 및 잔량의 용매를 포함하고, (i) 메타중아황산나트륨(Sodium metabisulfite), 아황산수소나트륨(Sodium bisulfite) 또는 이들의 혼합물, 및 (ii) bi-carboxylic acid, tri-carboxylic acid, 또는 이들의 혼합물을 합쳐서 조성물 총 중량 대비 0.1 내지 5 중량% 포함하며, 상기 (i) 성분 및 (ii) 성분은 3:7 내지 7:3 중량비로 포함하는, 히드로퀴논 또는 이의 유도체 함유 조성물을 제공한다.Another aspect of the present invention, based on the total weight of the composition, hydroquinone or a derivative thereof 0.1 to 10% by weight; 1 to 15% by weight of zinc oxide (ZnO), calamine, or a mixture thereof; and the remaining amount of a solvent, comprising (i) sodium metabisulfite, sodium bisulfite, or a mixture thereof, and (ii) bi-carboxylic acid, tri-carboxylic acid, or a mixture thereof. Including 0.1 to 5% by weight based on the total weight of the composition, the component (i) and the component (ii) are included in a weight ratio of 3:7 to 7:3, providing a composition containing hydroquinone or a derivative thereof.
본 개시에 따른 화장료 또는 약학 조성물은 본 발명의 목적을 저해하지 않는 범위 내에서 다양한 화장료 또는 약학 조성물용 첨가제를 포함할 수 있다. 이때 기타 첨가제는 상기 히드로퀴논 또는 이의 유도체; 금속 산화물 (바람직하게는, 산화아연(ZnO), 칼라민(Calamine), 티타늄다이옥사이드(TIO2) 또는 이들의 혼합물, 더욱 바람직하게는 산화아연, 칼라민 또는 이들의 혼합물); (i) 성분; 및 (ii) 성분을 제외한 중량을 차지하게 된다.The cosmetic or pharmaceutical composition according to the present disclosure may include various additives for a cosmetic or pharmaceutical composition within a range that does not impair the purpose of the present invention. In this case, other additives include the hydroquinone or derivatives thereof; metal oxides (preferably zinc oxide (ZnO), calamine, titanium dioxide (TIO 2 ) or mixtures thereof, more preferably zinc oxide, calamine or mixtures thereof); (i) a component; and (ii) excluding components.
예를 들어, 본 개시에 따른 화장료 조성물은 앞서 언급된 성분들 이외에 잔량의 용매를 함유할 수 있다. 즉, 히드로퀴논 또는 이의 유도체를 용해하는 물질로서, 물, 친수성 용매, 또는 이들의 혼합물은 상기 히드로퀴논 또는 이의 유도체; 산화아연(ZnO), 칼라민(Calamine), 티타늄다이옥사이드(TIO2) 등의 금속 산화물 또는 이들의 혼합물; (i) 성분; 및 (ii) 성분을 제외한 중량을 차지할 수 있다. 이러한 친수성 용매로는 다가 알코올 또는 휘발성 유기용매로 그 종류가 한정되지 않고 사용될 수 있다. 구체적으로는 폴리에틸렌글리콜, 프로필렌글라이콜, 디프로필렌글라이콜, 글리세린, 1,3-부탄디올, 아이소프로필알코올, 에탄올 등이 포함되지만 이제 제한되지는 않는다. 바람직하게는 아이소프로필알코올, 또는 에탄올이 사용될 수 있으며, 상기의 친수성 용매는 조성물의 총 중량에 대해 5~80 중량%의 양으로 사용할 수 있다. 친수성 용매의 사용이 본 발명에 있어서 제한적인 것은 아니나, 사용할 경우 히드로퀴논 또는 이의 유도체의 안정성에 도움이 될 수 있다. For example, the cosmetic composition according to the present disclosure may contain a residual amount of a solvent in addition to the above-mentioned ingredients. That is, as a substance for dissolving hydroquinone or a derivative thereof, water, a hydrophilic solvent, or a mixture thereof is selected from the group consisting of hydroquinone or a derivative thereof; Zinc oxide (ZnO), calamine (Calamine), titanium dioxide (TIO 2 ), such as metal oxides or mixtures thereof; (i) a component; and (ii) a weight excluding components. As the hydrophilic solvent, a polyhydric alcohol or a volatile organic solvent may be used without limitation. Specific examples include, but are not limited to, polyethylene glycol, propylene glycol, dipropylene glycol, glycerin, 1,3-butanediol, isopropyl alcohol, ethanol, and the like. Preferably, isopropyl alcohol or ethanol may be used, and the hydrophilic solvent may be used in an amount of 5 to 80% by weight based on the total weight of the composition. Although the use of a hydrophilic solvent is not limited in the present invention, when used, it may help the stability of hydroquinone or a derivative thereof.
본 개시에 따른 화장료 또는 약학 조성물은 해당분야에서 이용되는 통상의 제조법에 따라 제조될 수 있다. 예를 들어, 본 개시의 조성물은 스킨, 세럼, 젤, 로션, 크림, 파우더, 패치 등의 형태로 제형화되어 다양하게 적용될 수 있으며, 피부에 적용하게 되면 미백 효과의 효능을 제공할 수 있다.The cosmetic or pharmaceutical composition according to the present disclosure may be prepared according to a conventional manufacturing method used in the art. For example, the composition of the present disclosure may be formulated in the form of a skin, serum, gel, lotion, cream, powder, patch, etc. and applied in various ways, and when applied to the skin, it may provide the efficacy of a whitening effect.
본 발명에 기재된 모든 성분은, 바람직하게는, 한국, 중국, 미국, 유럽, 일본 등의 관련 법규, 규범 (예를 들어, 화장품 안전 기준 등에 관한 규정(한국), 화장품 안전 기술 규범(중국), 위생 규범(중국)) 등에서 규정한 최대사용치를 초과하지 않는다. 즉, 바람직하게, 본 발명에 따른 화장료, 약학 또는 퍼스널 케어용 조성물은 각국의 관련 법규, 규범에서 허용되는 함량 한도로 본 발명에 따른 성분들을 포함한다.All ingredients described in the present invention, preferably, relevant laws and regulations, such as Korea, China, the United States, Europe, Japan, etc. (for example, regulations on cosmetic safety standards (Korea), cosmetic safety technical standards (China), Do not exceed the maximum use value stipulated in sanitary standards (China), etc. That is, preferably, the composition for cosmetic, pharmaceutical or personal care according to the present invention contains the ingredients according to the present invention within the content limit allowed by the relevant laws and regulations of each country.
본 개시는 피부 자극이 개선되면서도 안정성이 확보된 히드로퀴논 또는 이의 유도체 함유 조성물을 제공한다. 구체적으로, 본 개시에 따른 조성물은 열, 산소, 빛 등과 같은 외부환경 요인 및 산화아연 등에 의한 히드로퀴논 또는 이의 유도체의 촉진된 산화반응을 방지함으로써 보존 안정성을 증가시키고, 변색을 예방해 독성을 감소시키고 염증반응을 줄일 수 있다. 본 개시의 조성물은 보존 안정성, 생체적합성, 피부 미백효능 등을 개선시킬 수 있어 미백개선용 화장품 및 의약품으로 널리 적용될 수 있다.The present disclosure provides a composition containing hydroquinone or a derivative thereof in which skin irritation is improved and stability is secured. Specifically, the composition according to the present disclosure increases storage stability by preventing the accelerated oxidation reaction of hydroquinone or a derivative thereof by external environmental factors such as heat, oxygen, light, etc. and zinc oxide, and reduces toxicity and inflammation by preventing discoloration reaction can be reduced. The composition of the present disclosure can improve storage stability, biocompatibility, skin whitening effect, and the like, and thus can be widely applied as cosmetics and pharmaceuticals for improving whitening.
도 1은 히드로퀴논과 금속산화물인 칼라민이 포함된 제제에서, 보존 안정성을 높이기 위해 사용된 항산화제 두 종류의 혼합 비율에 따른 변색 여부를 평가한 결과이다.1 is a result of evaluating whether or not discoloration according to the mixing ratio of two types of antioxidants used to increase storage stability in a formulation containing hydroquinone and calamine, a metal oxide.
도 2는 항산화제 종류에 따른 변색 감소 효과 평가 결과이다.2 is an evaluation result of discoloration reduction effect according to the type of antioxidant.
도 3은 항산화제 중 산(acid) 종류에 따른 변색 감소 효과 평가 결과이다.3 is an evaluation result of discoloration reduction effect according to the type of acid among antioxidants.
도 4는 두 종의 항산화제의 총 함량에 따른 변색 감소 효과 평가 결과이다.4 is an evaluation result of discoloration reduction effect according to the total content of two types of antioxidants.
이하, 본 발명의 이해를 돕기 위하여 실시예 등을 들어 상세하게 설명하기로 한다. 그러나, 본 발명에 따른 실시예들은 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 하기 실시예들에 한정되는 것으로 해석되어서는 안 된다. 본 발명의 실시예들은 본 발명이 속한 분야에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples and the like will be described in detail to help the understanding of the present invention. However, the embodiments according to the present invention may be modified in various other forms, and the scope of the present invention should not be construed as being limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art to which the present invention pertains.
[실시예 1~5 및 비교예 1~6][Examples 1 to 5 and Comparative Examples 1 to 6]
히드로퀴논과 금속산화물(칼라민) 복합 조성물에서 두 종류의 항산화제 비율에 따른 변색도 비교Comparison of discoloration according to the ratio of two types of antioxidants in hydroquinone and metal oxide (calamine) composite composition
하기 표 1에 나타난 조성대로 실시예 1~5 및 비교예 1~6을 제조하여 평가하였다.Examples 1 to 5 and Comparative Examples 1 to 6 were prepared and evaluated according to the composition shown in Table 1 below.
| 구성Configuration |
성분 (단위: 중량%)ingredient (Unit: % by weight) |
비교예 1Comparative Example 1 | 비교예 2Comparative Example 2 | 비교예 3Comparative Example 3 | 실시예 1Example 1 | 실시예 2Example 2 | 실시예 3Example 3 | 실시예 4Example 4 | 실시예 5Example 5 | 비교예 4Comparative Example 4 | 비교예 5Comparative Example 5 | 비교예 6 Comparative Example 6 |
| 유효성분active ingredient | 히드로퀴논hydroquinone | 44 | 44 | 44 | 44 | 44 | 44 | 44 | 44 | 44 | 44 | 44 |
| 금속산화물metal oxide | 칼라민calamine | 88 | 88 | 88 | 88 | 88 | 88 | 88 | 88 | 88 | 88 | 88 |
| 친수성 용매hydrophilic solvent | 디프로필렌글라이콜dipropylene glycol | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 |
| 친수성 용매hydrophilic solvent | 에탄올ethanol | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 |
| 항산화제 1antioxidant 1 | Citric acidCitric acid | 0.30.3 | 0.270.27 | 0.240.24 | 0.210.21 | 0.180.18 | 0.150.15 | 0.120.12 | 0.090.09 | 0.060.06 | 0.030.03 | -- |
| 항산화제 2antioxidant 2 | Sodium metabisulfiteSodium metabisulfite | -- | 0.030.03 | 0.060.06 | 0.090.09 | 0.120.12 | 0.150.15 | 0.180.18 | 0.210.21 | 0.240.24 | 0.270.27 | 0.30.3 |
| 변색도 ΔEDiscoloration ΔE | 19.119.1 | 27.827.8 | 19.519.5 | 2.02.0 | 1.91.9 | 1.81.8 | 1.41.4 | 2.52.5 | 18.418.4 | 21.121.1 | 18.318.3 |
구체적으로 다음과 같이 제조하였다. 상기 표 1의 비율에 따라 친수성 용매들과 항산화제1, 및 2를 상온에서 혼합하였다. 호모믹서를 이용하여 3000 rpm으로 교반하며 금속산화물인 칼라민을 투입하고, 분산하였다. 15분 간 교반하여 칼라민이 충분히 균질하게 분산되면, 히드로퀴논을 첨가하고 3000rpm으로 5분간 교반하여 완전히 용해시켰다.Specifically, it was prepared as follows. According to the ratio of Table 1, hydrophilic solvents and antioxidants 1 and 2 were mixed at room temperature. While stirring at 3000 rpm using a homomixer, calamine, a metal oxide, was added and dispersed. When the calamine was sufficiently homogeneously dispersed by stirring for 15 minutes, hydroquinone was added and the mixture was completely dissolved by stirring at 3000 rpm for 5 minutes.
변색도는 다음과 같이 측정하였다. 상기 표 1 조성물의 보존 안정성을 확인하기 위해 50℃에 4주간 보관하였다. 그 후 금속산화물이 침전되어 가라앉은 상층액을 96 well 불투명 white plate에 200ul씩 옮겨 담았다. 그 뒤, Chromameter CR-400(미놀타 사, 일본)로 L값(lightness), a값(redness), b값(yellowness)을 3회 반복 측정하였다. 전반적인 변색도는 
값으로 나타내었다.The degree of discoloration was measured as follows. In order to check the storage stability of the Table 1 composition, it was stored at 50° C. for 4 weeks. After that, the supernatant, in which the metal oxide was precipitated, was transferred to a 96-well opaque white plate by 200ul. Thereafter, L value (lightness), a value (redness), and b value (yellowness) were measured three times with a Chromameter CR-400 (Minolta, Japan). overall color change It is expressed as a value.
그 결과를 표 1 및 도 1에 나타내었다. 실시예 1~5과 같이 두 항산화제의 중량 비율이 3:7 ~ 7:3 비율일 때 변색도는 2.5 이하의 낮은 수치를 나타내었다. 반면, 비교예 1~6의 비율에서는 변색도가 18 이상으로 색차도가 높다. 따라서 안정성 개선에 두 항산화제 모두 필수적이라는 것을 알 수 있다. The results are shown in Table 1 and FIG. 1 . As in Examples 1 to 5, when the weight ratio of the two antioxidants was 3:7 to 7:3, the degree of discoloration showed a low value of 2.5 or less. On the other hand, in the ratios of Comparative Examples 1 to 6, the degree of discoloration was 18 or more, and the degree of color difference was high. Therefore, it can be seen that both antioxidants are essential for improving stability.
또한, 2가지 항산화제 모두 필수적이므로, 바람직하게는 2가지 항산화제를 특정 비율로 혼합하여 사용할 경우 금속산화물과 히드로퀴논의 복합 조성물에서 히드로퀴논의 보존 안정성을 높일 수 있다.In addition, since both antioxidants are essential, preferably, when the two antioxidants are mixed in a specific ratio and used, the storage stability of hydroquinone in a composite composition of metal oxide and hydroquinone can be improved.
[실시예 6~7 및 비교예 7~10][Examples 6-7 and Comparative Examples 7-10]
히드로퀴논과 금속산화물(칼라민) 복합 조성물에서 항산화제 종류에 따른 변색도 비교Comparison of discoloration according to antioxidant type in hydroquinone and metal oxide (calamine) composite composition
하기 표 2에 나타난 조성대로 실시예 6~7 및 비교예 7~10을 제조하여 평가하였다. 제조 방법 및 변색도 측정 방법은 상기 실시예 1~5의 방법들과 동일하였다.Examples 6 to 7 and Comparative Examples 7 to 10 were prepared and evaluated according to the composition shown in Table 2 below. The manufacturing method and the method of measuring the degree of discoloration were the same as those of Examples 1 to 5 above.
| 구성Configuration |
성분 (단위: 중량%)ingredient (Unit: % by weight) |
실시예 6Example 6 | 실시예 7Example 7 | 비교예 7Comparative Example 7 | 비교예 8Comparative Example 8 | 비교예 9Comparative Example 9 | 비교예 10Comparative Example 10 |
| 유효성분active ingredient | 히드로퀴논hydroquinone | 44 | 44 | 44 | 44 | 44 | 44 |
| 금속산화물metal oxide | 칼라민calamine | 88 | 88 | 88 | 88 | 88 | 88 |
| 친수성 용매hydrophilic solvent | 디프로필렌글라이콜dipropylene glycol | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 |
| 친수성 용매hydrophilic solvent | 에탄올ethanol | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 |
| 항산화제 1antioxidant 1 | Citric acidCitric acid | 0.20.2 | 0.20.2 | 0.20.2 | 0.20.2 | 0.20.2 | 0.20.2 |
| 항산화제 2-1Antioxidant 2-1 | Sodium metabisulfiteSodium metabisulfite | 0.10.1 | |||||
| 항산화제 2-2Antioxidants 2-2 | Sodium bisulfiteSodium bisulfite | 0.10.1 | |||||
| 항산화제 2-3Antioxidants 2-3 | Sodium sulfiteSodium sulfite | 0.10.1 | |||||
| 항산화제 2-4Antioxidants 2-4 | TocopherolTocopherol | 0.10.1 | |||||
| 항산화제 2-5Antioxidants 2-5 | Tocopheryl acetateTocopheryl acetate | 0.10.1 | |||||
| 항산화제 2-6Antioxidants 2-6 | BHTBHT | 0.10.1 | |||||
| 변색도 ΔEDiscoloration ΔE | 1.11.1 | 2.12.1 | 30.930.9 | 16.316.3 | 17.517.5 | 18.018.0 |
그 결과를 표 2 및 도 2에 나타내었다. 실시예 6과 7에서 변색도는 2.1 이하로 낮은 수치를 나타내었다. 반면, 비교예 7~10에서는 변색도가 16.3 이상으로 높다. 따라서, 항산화제의 종류는 실시예 6 및 7과 같은 종류를 사용해야만 금속산화물과 히드로퀴논의 복합 조성물에서 히드로퀴논의 보존 안정성을 높일 수 있다.The results are shown in Table 2 and FIG. 2 . In Examples 6 and 7, the degree of discoloration showed a low value of 2.1 or less. On the other hand, in Comparative Examples 7 to 10, the degree of discoloration was as high as 16.3 or more. Therefore, the storage stability of hydroquinone in the composite composition of the metal oxide and hydroquinone can be improved only by using the same types of antioxidants as in Examples 6 and 7.
[실시예 6, 8, 9 및 비교예 11~15][Examples 6, 8, 9 and Comparative Examples 11 to 15]
히드로퀴논과 금속산화물(칼라민) 복합 조성물에서 산(acid)의 종류에 따른 변색도 비교Comparison of discoloration according to the type of acid in the hydroquinone and metal oxide (calamine) composite composition
하기 표 3에 나타난 조성대로 실시예 6, 8, 9 및 비교예 11~15를 제조하여 평가하였다. 제조 방법 및 변색도 측정 방법은 상기 실시예 1~5의 방법들과 동일하였다.Examples 6, 8, 9 and Comparative Examples 11 to 15 were prepared and evaluated according to the composition shown in Table 3 below. The manufacturing method and the method of measuring the degree of discoloration were the same as those of Examples 1 to 5 above.
| 구성Configuration |
성분 (단위: 중량%)ingredient (Unit: % by weight) |
실시예 6Example 6 | 실시예 8Example 8 | 실시예 9Example 9 | 비교예 11Comparative Example 11 | 비교예 12Comparative Example 12 | 비교예 13Comparative Example 13 | 비교예 14Comparative Example 14 | 비교예 15Comparative Example 15 |
| 유효성분active ingredient | 히드로퀴논hydroquinone | 44 | 44 | 44 | 44 | 44 | 44 | 44 | 44 |
| 금속산화물metal oxide | 칼라민calamine | 88 | 88 | 88 | 88 | 88 | 88 | 88 | 88 |
| 친수성 용매hydrophilic solvent | 디프로필렌글라이콜dipropylene glycol | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 | 1010 |
| 친수성 용매hydrophilic solvent | 에탄올ethanol | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 | to 100to 100 |
| 항산화제 1-1Antioxidant 1-1 | Citric acidCitric acid | 0.20.2 | |||||||
| 항산화제 1-2Antioxidant 1-2 | Succinic acidsuccinic acid | 0.20.2 | |||||||
| 항산화제 1-3Antioxidants 1-3 | Adipic acidAdipic acid | 0.20.2 | |||||||
| 항산화제 1-4Antioxidants 1-4 | Lactic acidlactic acid | 0.20.2 | |||||||
| 항산화제 1-5Antioxidants 1-5 | Acetic acidAcetic acid | 0.20.2 | |||||||
| 항산화제 1-6Antioxidants 1-6 | Ferulic acidFerulic acid | 0.20.2 | |||||||
| 항산화제 1-7Antioxidants 1-7 | Benzoic acidBenzoic acid | 0.20.2 | |||||||
| 항산화제 1-8Antioxidants 1-8 | Sorbic acidSorbic acid | 0.20.2 | |||||||
| 항산화제 2antioxidant 2 | Sodium metabisulfiteSodium metabisulfite | 0.10.1 | 0.10.1 | 0.10.1 | 0.10.1 | 0.10.1 | 0.10.1 | 0.10.1 | 0.10.1 |
| 변색도 ΔEDiscoloration ΔE | 1.11.1 | 1.71.7 | 2.42.4 | 37.937.9 | 31.831.8 | 33.333.3 | 28.928.9 | 29.429.4 |
그 결과를 표 3 및 도 3에 나타내었다. 실시예 6, 8 및 9와 같이 항산화제로 사용된 acid의 종류가 di- 또는 tri-carboxylic acid일 때 변색도는 2.4 이하로 낮았다. 그러나, 비교예 11~15와 같은 다른 acid를 사용하는 경우는 변색도가 28.9 이상으로 높았다. 따라서, 항산화제 중 acid의 종류는 di- 또는 tri-carboxylic acid를 사용해야만 금속산화물과 히드로퀴논의 복합 조성물에서 히드로퀴논의 보존 안정성을 높일 수 있다.The results are shown in Table 3 and FIG. 3 . As in Examples 6, 8 and 9, when the type of acid used as an antioxidant was di- or tri-carboxylic acid, the degree of discoloration was as low as 2.4 or less. However, when other acids such as Comparative Examples 11 to 15 were used, the degree of discoloration was as high as 28.9 or more. Therefore, as the type of acid among antioxidants, di- or tri-carboxylic acid can be used to increase the storage stability of hydroquinone in the composite composition of metal oxide and hydroquinone.
[실시예 3, 10 및 11][Examples 3, 10 and 11]
히드로퀴논과 금속산화물(칼라민) 복합 조성물에서 두 종류의 항산화제 총량에 따른 변색도 비교Comparison of discoloration according to the total amount of two types of antioxidants in hydroquinone and metal oxide (calamine) composite composition
하기 표 4에 나타난 조성대로 실시예 3, 10, 및 11을 제조하여 평가하였다. 제조 방법 및 변색도 측정 방법은 상기 실시예 1~5의 방법들과 동일하였다.Examples 3, 10, and 11 were prepared and evaluated according to the composition shown in Table 4 below. The manufacturing method and the method of measuring the degree of discoloration were the same as those of Examples 1 to 5 above.
| 구성Configuration | 성분 (단위: 중량%)Ingredients (unit: wt%) | 실시예 3Example 3 | 실시예 10Example 10 | 실시예 11Example 11 |
| 유효성분active ingredient | 히드로퀴논hydroquinone | 44 | 44 | 44 |
| 금속산화물metal oxide | 칼라민calamine | 88 | 88 | 88 |
| 친수성 용매hydrophilic solvent | 디프로필렌글라이콜dipropylene glycol | 1010 | 1010 | 1010 |
| 친수성 용매hydrophilic solvent | 에탄올ethanol | to 100to 100 | to 100to 100 | to 100to 100 |
| 항산화제 1antioxidant 1 | Citric acidCitric acid | 0.150.15 | 0.10.1 | 0.050.05 |
| 항산화제 2antioxidant 2 | Sodium metabisulfiteSodium metabisulfite | 0.150.15 | 0.10.1 | 0.050.05 |
| 변색도 ΔEDiscoloration ΔE | 1.81.8 | 2.12.1 | 6.16.1 |
그 결과를 표 4와 도 4에 나타내었다. 즉, 상기 표 1에서 확인한, 두 항산화제의 비율 (1:1 중량비)에서 항산화제의 총량을 달리하며 조성물의 변색도를 평가하였다. 표 4 및 도 4에 나타나는 바와 같이, 실시예 3, 10, 및 11 모두 변색도는 6.1 이하의 낮은 수치를 나타내었다. 따라서 두 항산화제를 특정 비율로 혼합하고 그 총량이 0.1 중량% 이상일 때, 금속산화물과 히드로퀴논의 복합 조성물에서 히드로퀴논에 대한 산화 방지 효과가 우수하다.The results are shown in Table 4 and FIG. 4 . That is, the discoloration degree of the composition was evaluated by varying the total amount of antioxidants in the ratio (1:1 weight ratio) of the two antioxidants confirmed in Table 1 above. As shown in Table 4 and FIG. 4, in Examples 3, 10, and 11, the discoloration degree showed a low value of 6.1 or less. Therefore, when the two antioxidants are mixed in a specific ratio and the total amount is 0.1% by weight or more, the antioxidant effect on hydroquinone is excellent in the composite composition of the metal oxide and hydroquinone.
Claims (8)
- 유효 성분으로 히드로퀴논 또는 이의 유도체를 함유하고, 금속 산화물을 추가로 포함하는 조성물에 있어서, In the composition comprising hydroquinone or a derivative thereof as an active ingredient, and further comprising a metal oxide,히드로퀴논 또는 이의 유도체의 안정성 개선을 위해 (i) 메타중아황산나트륨(Sodium metabisulfite), 아황산수소나트륨(Sodium bisulfite) 또는 이들의 혼합물, 및 (ii) bi-carboxylic acid, tri-carboxylic acid, 또는 이들의 혼합물을 포함하는 것을 특징으로 하는, 히드로퀴논 또는 이의 유도체 함유 조성물. To improve the stability of hydroquinone or derivatives thereof (i) sodium metabisulfite (Sodium metabisulfite), sodium bisulfite (Sodium bisulfite) or mixtures thereof, and (ii) bi-carboxylic acid, tri-carboxylic acid, or mixtures thereof A composition containing hydroquinone or a derivative thereof, characterized in that it comprises a.
- 제1항에 있어서, 상기 히드로퀴논의 유도체는 히드로퀴논 모노벤질 에테르, 히드로퀴논 모노메틸 에테르, 히드로퀴논 모노에틸 에테르, 아르부틴(arbutin), 4-하이드록시아니솔(4-hydroxyanisol), t-부틸 히드로퀴논, 4-[(테트라하이드로-2H-피란-2-일)옥시]페놀, 4-[(테트라하이드로-2H-티오피란-2-일)옥시]페놀, 및 히드로퀴논 글루코사이드 유도체로 이루어진 군으로부터 선택된 어느 하나 이상인, 조성물. The method of claim 1, wherein the hydroquinone derivative is hydroquinone monobenzyl ether, hydroquinone monomethyl ether, hydroquinone monoethyl ether, arbutin, 4-hydroxyanisol, t-butyl hydroquinone, 4 -[(tetrahydro-2H-pyran-2-yl)oxy]phenol, 4-[(tetrahydro-2H-thiopyran-2-yl)oxy]phenol, and at least one selected from the group consisting of hydroquinone glucoside derivatives , composition.
- 제1항에 있어서, 상기 bi-carboxylic acid 또는 tri-carboxylic acid는 사과산(malic acid), 숙신산(succinic acid), 주석산(tartaric acid), 말레산(maleic acid), 푸마르산(fumaric acid), 구연산(citric acid), 아디프산(adipic acid), 옥살산(oxalic acid), 말론산(malonic acid), 글루타르산 (glutaric acid), 글루타콘산(glutaconic acid), 세바스산 (sebacic acid), 아젤라인산 (azelaic acid), 피멜산 (pimelic acid), 아이소시트르산 (isocitric acid), 아코니트산 (aconitic acid), 아가르산(agaric acid), 이타콘산 (itaconic acid), 시트라코닉산 (citraconic acid), 뮤콘산 (muconic acid), 글루티닉산(glutinic acid) 또는 이들의 혼합물인, 조성물. According to claim 1, wherein the bi-carboxylic acid or tri-carboxylic acid is malic acid (malic acid), succinic acid (succinic acid), tartaric acid (tartaric acid), maleic acid (maleic acid), fumaric acid (fumaric acid), citric acid ( citric acid, adipic acid, oxalic acid, malonic acid, glutaric acid, glutaconic acid, sebacic acid, azelaic acid (azelaic acid), pimelic acid, isocitric acid, aconitic acid, agaric acid, itaconic acid, citraconic acid , muconic acid (muconic acid), glutinic acid (glutinic acid) or a mixture thereof, the composition.
- 제1항에 있어서, 상기 금속 산화물은 산화아연(ZnO), 칼라민(Calamine), 또는 이들의 혼합물인, 조성물.The composition of claim 1 , wherein the metal oxide is zinc oxide (ZnO), calamine, or a mixture thereof.
- 제1항에 있어서, 상기 조성물은 (i) 메타중아황산나트륨(Sodium metabisulfite), 및 (ii) 구연산, 숙신산, 아디프산, 주석산 또는 이들의 혼합물을 포함하는, 조성물. The composition of claim 1 , wherein the composition comprises (i) sodium metabisulfite, and (ii) citric acid, succinic acid, adipic acid, tartaric acid, or mixtures thereof.
- 제1항 내지 제5항 중 어느 한 항에 있어서, 상기 조성물은 (i) 메타중아황산나트륨(Sodium metabisulfite), 아황산수소나트륨(Sodium bisulfite) 또는 이들의 혼합물, 및 (ii) bi-carboxylic acid, tri-carboxylic acid, 또는 이들의 혼합물을 3:7 내지 7:3 중량비 ((i):(ii))로 포함하는, 조성물. According to any one of claims 1 to 5, wherein the composition is (i) sodium metabisulfite (Sodium metabisulfite), sodium bisulfite (Sodium bisulfite) or mixtures thereof, and (ii) bi-carboxylic acid, tri A composition comprising -carboxylic acid, or a mixture thereof, in a weight ratio of 3:7 to 7:3 ((i):(ii)).
- 제6항에 있어서, 상기 조성물은 (i) 메타중아황산나트륨(Sodium metabisulfite), 아황산수소나트륨(Sodium bisulfite) 또는 이들의 혼합물, 및 (ii) bi-carboxylic acid, tri-carboxylic acid, 또는 이들의 혼합물의 총 함량이 조성물 총 중량 대비 0.1 내지 10 중량%인, 조성물. According to claim 6, wherein the composition is (i) sodium metabisulfite (Sodium metabisulfite), sodium bisulfite (Sodium bisulfite) or a mixture thereof, and (ii) bi-carboxylic acid, tri-carboxylic acid, or a mixture thereof The total content of the composition is 0.1 to 10% by weight based on the total weight of the composition.
- 조성물 총 중량 대비, 히드로퀴논 또는 이의 유도체 0.1 내지 10 중량%; 산화아연(ZnO), 칼라민(Calamine), 또는 이들의 혼합물 1 내지 15 중량%; 및 잔량의 용매를 포함하고, 0.1 to 10% by weight of hydroquinone or a derivative thereof, based on the total weight of the composition; 1 to 15% by weight of zinc oxide (ZnO), calamine, or a mixture thereof; and the remainder of the solvent,(i) 메타중아황산나트륨(Sodium metabisulfite), 아황산수소나트륨(Sodium bisulfite) 또는 이들의 혼합물, 및 (ii) bi-carboxylic acid, tri-carboxylic acid, 또는 이들의 혼합물을 합쳐서 조성물 총 중량 대비 0.1 내지 5 중량% 포함하며, (i) sodium metabisulfite (Sodium metabisulfite), sodium bisulfite (Sodium bisulfite) or a mixture thereof, and (ii) bi-carboxylic acid, tri-carboxylic acid, or a mixture thereof 0.1 to 5 based on the total weight of the composition Including weight %,상기 (i) 성분 및 (ii) 성분은 3:7 내지 7:3 중량비로 포함하는, The (i) component and (ii) component comprising in a weight ratio of 3:7 to 7:3,히드로퀴논 또는 이의 유도체 함유 조성물.A composition containing hydroquinone or a derivative thereof.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20200142222 | 2020-10-29 | ||
| KR10-2020-0142222 | 2020-10-29 | ||
| KR1020210114285A KR20220057415A (en) | 2020-10-29 | 2021-08-27 | Stabilized composition comprising hydroquinone or its derivative |
| KR10-2021-0114285 | 2021-08-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022092639A1 true WO2022092639A1 (en) | 2022-05-05 |
Family
ID=81311955
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2021/014281 WO2022092639A1 (en) | 2020-10-29 | 2021-10-14 | Stabilization composition including hydroquinone or derivative thereof |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN114425024A (en) |
| TW (1) | TW202220640A (en) |
| WO (1) | WO2022092639A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115006279A (en) * | 2022-06-21 | 2022-09-06 | 沈阳药科大学 | Clathrate compound and preparation method thereof, external preparation and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09263513A (en) * | 1996-03-29 | 1997-10-07 | Shiseido Co Ltd | Preparation for external use for skin |
| JP2000204019A (en) * | 1999-01-14 | 2000-07-25 | Pola Chem Ind Inc | Makeup cosmetic having bleaching effect |
| JP2004099542A (en) * | 2002-09-10 | 2004-04-02 | Rikogaku Shinkokai | Bleaching agent containing crystalline molecular complex of hydroquinone with surfactant |
| EP2047846A2 (en) * | 2001-05-23 | 2009-04-15 | Medicis Pharmaceutical Corporation | Process for stabilizing hydroquinone |
| KR20160014271A (en) * | 2014-07-29 | 2016-02-11 | 동아제약 주식회사 | Low irritating composition for skin whitening comprising hydroquinone |
-
2021
- 2021-10-14 CN CN202111197165.9A patent/CN114425024A/en active Pending
- 2021-10-14 WO PCT/KR2021/014281 patent/WO2022092639A1/en active Application Filing
- 2021-10-28 TW TW110140168A patent/TW202220640A/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09263513A (en) * | 1996-03-29 | 1997-10-07 | Shiseido Co Ltd | Preparation for external use for skin |
| JP2000204019A (en) * | 1999-01-14 | 2000-07-25 | Pola Chem Ind Inc | Makeup cosmetic having bleaching effect |
| EP2047846A2 (en) * | 2001-05-23 | 2009-04-15 | Medicis Pharmaceutical Corporation | Process for stabilizing hydroquinone |
| JP2004099542A (en) * | 2002-09-10 | 2004-04-02 | Rikogaku Shinkokai | Bleaching agent containing crystalline molecular complex of hydroquinone with surfactant |
| KR20160014271A (en) * | 2014-07-29 | 2016-02-11 | 동아제약 주식회사 | Low irritating composition for skin whitening comprising hydroquinone |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115006279A (en) * | 2022-06-21 | 2022-09-06 | 沈阳药科大学 | Clathrate compound and preparation method thereof, external preparation and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114425024A (en) | 2022-05-03 |
| TW202220640A (en) | 2022-06-01 |
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