JPS6324968B2 - - Google Patents
Info
- Publication number
- JPS6324968B2 JPS6324968B2 JP61020587A JP2058786A JPS6324968B2 JP S6324968 B2 JPS6324968 B2 JP S6324968B2 JP 61020587 A JP61020587 A JP 61020587A JP 2058786 A JP2058786 A JP 2058786A JP S6324968 B2 JPS6324968 B2 JP S6324968B2
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- kojic acid
- added
- derivatives
- skin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 106
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 52
- 229930003427 Vitamin E Natural products 0.000 claims description 51
- 229940046009 vitamin E Drugs 0.000 claims description 51
- 235000019165 vitamin E Nutrition 0.000 claims description 51
- 239000011709 vitamin E Substances 0.000 claims description 51
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 claims description 32
- 229960004705 kojic acid Drugs 0.000 claims description 22
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 claims description 22
- 150000003712 vitamin E derivatives Chemical class 0.000 claims description 19
- 239000007864 aqueous solution Substances 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- 230000008099 melanin synthesis Effects 0.000 claims description 11
- 239000007900 aqueous suspension Substances 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- -1 flavonol compounds Chemical class 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 14
- 239000002502 liposome Substances 0.000 description 12
- 239000008213 purified water Substances 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 239000002537 cosmetic Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 150000003904 phospholipids Chemical class 0.000 description 8
- 239000000839 emulsion Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000006210 lotion Substances 0.000 description 7
- 239000002674 ointment Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 239000004094 surface-active agent Substances 0.000 description 7
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 6
- 206010040829 Skin discolouration Diseases 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000004359 castor oil Substances 0.000 description 5
- 235000019438 castor oil Nutrition 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 5
- 229960000984 tocofersolan Drugs 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 4
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 4
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 4
- 229940058015 1,3-butylene glycol Drugs 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 3
- 239000004166 Lanolin Substances 0.000 description 3
- 150000005215 alkyl ethers Chemical class 0.000 description 3
- 235000019437 butane-1,3-diol Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004040 coloring Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 235000019388 lanolin Nutrition 0.000 description 3
- 229940039717 lanolin Drugs 0.000 description 3
- 239000000787 lecithin Substances 0.000 description 3
- 235000010445 lecithin Nutrition 0.000 description 3
- 229940067606 lecithin Drugs 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 229940042585 tocopherol acetate Drugs 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 235000001809 DL-alpha-tocopherylacetate Nutrition 0.000 description 2
- 239000011626 DL-alpha-tocopherylacetate Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 239000004909 Moisturizer Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 239000012062 aqueous buffer Substances 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229960000735 docosanol Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229940009662 edetate Drugs 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 239000010696 ester oil Substances 0.000 description 2
- 229940075507 glyceryl monostearate Drugs 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- 230000001333 moisturizer Effects 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 2
- 229930182490 saponin Natural products 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229940032094 squalane Drugs 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 2
- 229940099259 vaseline Drugs 0.000 description 2
- 230000002087 whitening effect Effects 0.000 description 2
- WGVKWNUPNGFDFJ-DQCZWYHMSA-N β-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C WGVKWNUPNGFDFJ-DQCZWYHMSA-N 0.000 description 2
- DSEKYWAQQVUQTP-XEWMWGOFSA-N (2r,4r,4as,6as,6as,6br,8ar,12ar,14as,14bs)-2-hydroxy-4,4a,6a,6b,8a,11,11,14a-octamethyl-2,4,5,6,6a,7,8,9,10,12,12a,13,14,14b-tetradecahydro-1h-picen-3-one Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3C[C@@H](O)C(=O)[C@@H]1C DSEKYWAQQVUQTP-XEWMWGOFSA-N 0.000 description 1
- LZSPGQAJYDEOLQ-UHFFFAOYSA-N (5-hydroxy-4-oxopyran-2-yl)methyl 3-phenylprop-2-enoate Chemical compound O=C1C(O)=COC(COC(=O)C=CC=2C=CC=CC=2)=C1 LZSPGQAJYDEOLQ-UHFFFAOYSA-N 0.000 description 1
- VXIKPSLGUZSZPG-UHFFFAOYSA-N (5-hydroxy-4-oxopyran-2-yl)methyl benzoate Chemical compound O=C1C(O)=COC(COC(=O)C=2C=CC=CC=2)=C1 VXIKPSLGUZSZPG-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000010445 Chilblains Diseases 0.000 description 1
- 206010008528 Chillblains Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- IELOKBJPULMYRW-NJQVLOCASA-N D-alpha-Tocopheryl Acid Succinate Chemical compound OC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C IELOKBJPULMYRW-NJQVLOCASA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 241000490229 Eucephalus Species 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- SPAGIJMPHSUYSE-UHFFFAOYSA-N Magnesium peroxide Chemical compound [Mg+2].[O-][O-] SPAGIJMPHSUYSE-UHFFFAOYSA-N 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- CVQUWLDCFXOXEN-UHFFFAOYSA-N Pyran-4-one Chemical compound O=C1C=COC=C1 CVQUWLDCFXOXEN-UHFFFAOYSA-N 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
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- 239000003963 antioxidant agent Substances 0.000 description 1
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- 235000021302 avocado oil Nutrition 0.000 description 1
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- 210000004027 cell Anatomy 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229940099418 d- alpha-tocopherol succinate Drugs 0.000 description 1
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
- 235000011957 flavonols Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000010382 gamma-tocopherol Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 230000002650 habitual effect Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960004995 magnesium peroxide Drugs 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229940060184 oil ingredients Drugs 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 208000000995 spontaneous abortion Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- PLVWNARVBMHCST-UHFFFAOYSA-L zinc;oxidooxy(oxo)borane Chemical compound [Zn+2].[O-]OB=O.[O-]OB=O PLVWNARVBMHCST-UHFFFAOYSA-L 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 235000007680 β-tocopherol Nutrition 0.000 description 1
- 239000011590 β-tocopherol Substances 0.000 description 1
- 239000002478 γ-tocopherol Substances 0.000 description 1
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- 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
- A61K8/67—Vitamins
- A61K8/678—Tocopherol, i.e. vitamin E
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
Description
〔産業上の利用分野〕
本発明はメラニン生成抑制作用を有する外用剤
に関するものである。
〔従来の技術〕
人の肌を白くする、いわゆる色白化粧料は、古
くから過酸化水素、過酸化マグネシウム、過酸化
ナトリウム、過ホウ酸亜鉛などの過酸化物を配合
した化粧料が使用されていた。しかしながら、こ
れらの過酸化物は極めて不安定な物質であるた
め、保存性あるいは化粧料基剤への配合などに難
点があり、更にその色白効果も十分であるとはい
えなかつた。近時、ビタミンC、システイン、コ
ロイド硫黄などを配合した化粧料が色白の目的で
用いられるようになつたが、なおその効果は十分
満足するものは得られなかつた。さらに、コウジ
酸を用いた色白化粧料(特公昭56−18569号公
報)、コウジ酸の誘導体を含有する色白化粧料
(特開昭56−79616号、特開昭56−7710号、特開昭
59−33207号公報等)が知られている。また、ク
エルセチン、フラボノール系化合物を含有する色
白化粧料(特開昭55−92305号、特開昭55−
111410号、特開昭55−111411号、特開昭55−
143908号公報等)が知られている。
一方、ビタミンEは習慣性流産、筋萎縮症、末
梢血管障害、心臓疾患などに用いられる医薬であ
り、主として内服又は、油溶液の注射剤として用
いられている。また、末梢血管の拡張作用がある
ため、ビタミンEを軟膏として製剤化し、「しも
やけ」の薬として市販されている。更にビタミン
Eは上記医薬としての効果の他、還元性作用があ
るので酸化防止剤として化粧料、医薬剤などに加
えて用いている。
更に、また、ビタミンEをリポソームとして水
に溶解し、美白化粧水とし、チロシローゼ活性阻
害するとの記載も開示されている(特開昭56−
75421号公報)。
〔発明が解決しようとする問題点〕
従来の技術において、色白化粧料に用いる色白
成分の内、過酸化物はその作用が皮膚に生成した
メラニンなどの色素を直接酸化漂白したもので、
過度の使用は皮膚本来の色も漂白し皮膚が白色に
なり不都合であつた。
また、コウジ酸、フラノボールなどはメラニン
生成を抑制するものであり、有用な色白化粧料と
して用いられるものである。しかし、本物質を長
期間保存するとコウジ酸などによる着色が生ずる
場合がある。
〔問題点を解決するための手段〕
本発明者らは先に、ビタミンE又はビタミンE
誘導体のメラニン生成抑制について研究し、ビタ
ミンEの水溶液がチロシナーゼ活性を阻害しない
のに、メラニン生成抑制作用が極めて優れている
驚くべき事実をマウス黒色腫由来のB16細胞によ
る試験により確認し、ビタミンE及び/又はその
誘導体を溶解又は懸濁状態で含有させたメラニン
生成抑制外用薬剤を発明し特願昭60−246890号と
して出願した。
今般、上記ビタミンE及び/又はその誘導体の
溶解又は懸濁状態で外用基剤の水相に含有させた
液にコウジ酸を配合したところ、ビタミンEとコ
ウジ酸は相乗効果による極めて著しいメラニン生
成抑制の効果が発現し、更にコウジ酸を含有する
外用剤において長期間の保存により生ずる着色が
全く見られない効果も見い出し本発明を完成し
た。
本発明はコウジ酸及び/又はコウジ酸誘導体の
水溶液とビタミンE及び/又はビタミンE誘導体
の水溶液又は懸濁液を含有することを特徴とする
メラニン生成抑制外用剤である。
本発明に使用するコウジ酸誘導体としては2−
ベンゾイルオキシメチル−5−ヒドロキシ−4H
−ピラン−4−オン、2−シンナモイルオキシメ
チル−5−ヒドロキシ−4H−ピラン−4−オン、
2−フエノキシメチル−5−ヒドロキシ−4H−
ピラン−4−オンなどが含まれる。
本発明に使用するビタミンE、ビタミンE誘導
体としては天然ビタミンE油、α−トコフエロー
ル、β−トコフエロール、γ−トコフエロールな
どのビタミンE及びビタミンEアセテート、ビタ
ミンEサクシネートなどのビタミンE誘導体及び
その塩類が含まれる。
外用剤は、乳剤、軟膏剤、パスタ剤、パツプ
剤、ローシヨン剤などの形態で皮膚に塗布するこ
とにより皮膚に生成するメラニンを抑制し、皮膚
の黒、褐色の色を除去し、さらに生成を防止する
ものである。
上記ビタミンE、ビタミンE誘導体の単独又は
それらの2種以上の混合物は前記外用薬剤の水相
部に溶解させるには、ビタミンE及び/又はビタ
ミンE誘導体をリン脂質とリポソームを形成させ
る水溶化する方法、ビタミンE及び/又はビタミ
ンE誘導体を界面活性剤、キヤラサポニン等のサ
ポニン類のビタミンE可溶化剤の存在下で水溶化
させる方法などにより水溶液とするか、ビタミン
E、ビタミンE誘導体を有機溶媒に溶かした有機
溶媒溶液とするかして外用剤の水相部に配合す
る。なお、上記ビタミンE、ビタミンE誘導体は
水相に完全に溶解せず、一部懸濁状態になつてい
てもビタミンE等が相中に分離しなければ本発明
の外用剤として使用でき、かつ効果も充分奏する
ことができる。また懸濁状態で外用剤の水相部に
配合させてもよい。この場合懸濁剤としては界面
活性剤、リン脂質などが用いられる。
前記のビタミンE及び/又はビタミンE誘導体
を水溶化する場合、ビタミンE、ビタミンE誘導
体のリポソームを形成させる場合は、一般のリポ
ソームの製法に従つて、卵黄レシチン、大豆レシ
チンなど天然レシチン及びジステアロイルレシチ
ンなど合成レシチンのリン脂質を用いてビタミン
E類含有リポソームとする。その製法としてリン
脂質とビタミンE類をクロロホルム、ベンゼンな
どの溶媒に溶かし、これをロータリーエバポレー
ターを用いて溶媒を減圧留去し、生成した薄膜に
緩衝水溶液を加えて激しく振り膨潤させて多重層
リポソームを製造し、更に超音波を照射して1枚
膜リポソームを製造する方法、リン脂質とビタミ
ンE類を有機溶媒に溶解し、この溶液を撹拌中の
緩衝剤水溶液に注加して、リポソームを製造する
方法、リン脂質とビタミンE類をクロロホルム、
ベンゼンなどの溶媒に溶かし、これに緩衝剤水溶
液を加え、超音波により油中水型に乳化させ、ロ
ータリーエバポレーターで溶媒を留去し、ボルテ
ツクスにより水中油型に転相してリポソームを製
造する方法などの公知の製法によつて製造され
る。
ビタミンE、ビタミンE誘導体を界面活性剤を
用いて、水に可溶化する場合は非イオン界面活性
剤、例えばポリエチレングリコール脂肪酸エステ
ル、ポリオキシエチレンソルビタン脂肪酸エステ
ル、ポリオキシエチレングリセリン脂肪酸エステ
ル、、ポリグリセリン脂肪酸エステル、ポリオキ
シエチレンヒマシ油、ポリオキシエチレンフイト
ステロール、ポリオキエチレンラノリン誘導体、
ポリオキシエチレンアルキルエーテル、ポリオキ
シエチレンポリオキシプロピレンアルキルエーテ
ルなど、陰イオン界面活性剤例えばアルキルエー
テルリン酸などが用いられHLB15以上のものが
好適である。また、上記界面活性剤にエタノー
ル、プロピレングリコールなどを添加すると更に
可溶化度が良好となる。
またビタミンE、ビタミンE誘導体を懸濁させ
るには、懸濁剤として上記リン脂質、界面活性剤
などを添加して行う。
本発明に使用するコウジ酸、コウジ酸誘導体及
びビタミンE、ビタミンE誘導体の外用剤に含有
させる量は、コウジ酸、コウジ酸誘導体は0.1〜
3.0%(重量)、ビタミンE、ビタミンE誘導体は
0.01〜1.0%(重量)が好適である。
本発明の外用剤は主として乳剤、軟膏剤、パス
タ剤、パツプ剤、ローシヨン剤等の製剤形であ
り、それらの各外用剤に通常使用される基剤、助
剤等に上記コウジ酸、コウジ酸誘導体、及びビタ
ミンE、ビタミンE誘導体を0.11〜4.0%(重量)
になるように加えて外用剤とする。
例えば、ローシヨン剤においては、精製水にグ
リセリン、プロピレングリコールなどの保湿剤、
皮膚栄養剤などをアルコールに溶解し、両者を混
合して室温下に可溶化する一般のローシヨン剤の
製造において、水溶部又はアルコール部にコウジ
酸、コウジ酸誘導体の水溶液及び、ビタミンE、
ビタミンE誘導体の水溶液又は懸濁液を前記の含
有量になるように加えてローシヨン剤とする。
軟膏剤においては、精製水に親水性成分例えば
グリセリン、ソルビツト等の保湿剤を添加して水
相部とし、油相部は、ミツロウ、パラフイン、マ
イクロクリスタリンワツクス、セレシン、高級脂
肪酸、硬化油等の固形油分、ワセリン、ラノリ
ン、グリセリド等の半固形油分、それにスクワラ
ン、流動パラフイン、各種エステル油等の液状油
分に防腐剤、界面活性剤等の油性成分を添加し調
整する。この様にして得らた水相部を加温して、
ゆるやかに撹拌しつつ、同温度に加温された油相
部を徐々に添加し乳化して軟膏剤とする一般の製
造において、水相部にコウジ酸、コウジ酸誘導体
の水溶液及びビタミンE、ビタミンE誘導体の水
溶液又は懸濁液を前記の含有量になるように加え
て軟膏剤とする。
乳剤においては、精製水にグリセリン等の保湿
剤、酸又はアルカリのPH調整剤等を加え加熱混合
してエタノールを加え水相部とし、ミツロウ、パ
ラフイン等の固形油分、ワセリン、ラノリン等の
半固形油分、スクワラン、流動パラフイン、各種
エステル油等の液状油分に、防腐剤、界面活性剤
等の油性成分を添加調整して混合加熱し油相部と
し、油相部を水相部に加えて予備乳化を行い、こ
れにカルボキシビニルポリマー、カルボキシメチ
ルセルロース等の保護コロイド剤を加え、ホモミ
キサーで均一に乳化して乳剤とする一般の乳剤の
製造において、水相部にコウジ酸、コウジ酸誘導
体の水溶液及びビタミンE、ビタミンE誘導体の
水溶液又は懸濁液を前記の含有量になるように加
えて乳剤とする。
パツプ剤においては、精製水にグリセリン等の
保湿剤、ポリビニルアルコール、ビーガム等の皮
膜剤等を加えて膨潤させ、これに必要があればカ
オリン、タルク、酸化亜鉛等の粉末を加え、香
料、防腐剤等を溶解したエタノールを加えてペー
スト状となるまで混練する一般のパツプ剤の製造
において、コウジ酸、コウジ酸誘導体の水溶液及
びビタミンE、ビタミンE誘導体の水溶液又は懸
濁液を前記の含量になるように加えてパツプ剤と
する。
〔実施例〕
例 1
(ローシヨン剤)
1 ポリオキシエチレン硬化ヒマシ油(60E.0)
1.00%
2 香料 微量
3 エタノール 15.00%
4 パラオキシ安息香酸エステル 0.10%
5 クエン酸 0.10%
6 クエン酸ナトリウム 0.30%
7 1,3−ブチレングリコール 4.00%
*8 天然ビタミンE可溶化液 5.00%
9 エデト酸二ナトリウム 0.01%
10 コウジ酸 0.50%
上記1〜10の成分に精製水を加えて、均一に撹
拌、溶解し、これを容器に充填し、検査後製品と
する。
(天然ビタミンE可溶液の調製方法)
1 天然ビタミンE 1.00%
2 ポリオキシエチレン硬化ヒマシ油(60E.0)
4.00%
3 ポリエチレングリコール400 8.00%
4 エタノール 16.00%
5 精製水を加えて、全量を100gとする。
上記成分1〜5を均一に撹拌、混合する。
例 2
(パツプ剤)
1 ポリビニルアルコール 10.00%
2 濃グリセリン 2.00%
3 エタノール4.00%
4 パラオキシ安息香酸エステル 0.20%
5 酸化チタン 2.00%
6 カオリン 1.00%
*7 酢酸dl−α−トコフエロール可溶化液
10.00%
8 エデト酸二ナトリウム 0.01%
9 コウジ酸 1.00%
10 香料 微量
上記成分1を精製水に加温、溶解し、これに成
分2,4,5,6を加えて混合し、冷却する。こ
れに成分3及び7,8,9,10を加え、撹拌、混
合する。これを冷却後、容器に充填し、検査後製
品とする。
(酢酸dl−α−トコフエロール可溶化液の調製方
法)
1 酢酸dl−α−トコフエロール 1.00%
2 ポリオキシエチレンヒマシ油(50E.0.)
4.00%
3 ポリエチレングリコール400 8.00%
4 エタノール 16.00%
上記成分に精製水を加え全量を100gとし均一
に撹拌、混合する。
例 3
(乳剤)
1 モノステアリン酸ポリオキシエチレンソルビ
タン(20E.0.) 1.00%
2 テトラオレイン酸ポリオキシエチレンソルビ
ツト(60E.0) 0.50%
3 親油型モノステアリン酸グリセリン 1.00%
4 ステアリン酸 0.50%
5 ベヘニルアルコール 0.50%
6 アボカド油 4.00%
7 トリオクタン酸グリセリル 4.00%
8 パラオキシ安息香酸エステル 0.20%
9 1,3−ブチレングリコール 5.00%
10 キサンタンガム 0.14%
*11 天然ビタミンEリポソーム液 5.00%
12 エデト酸二ナトリウム 0.01%
13 コウジ酸 1.00%
14 香料 微量
上記成分1〜14に精製水を加えて、容器に充填
し製品とする。
(天然ビタミンEリポソーム液の調製方法)
1 天然ビタミンE 1.00%
2 卵黄レシチン 4.00%
3 ポイエチレングリコール400 8.00%
4 エタノール 16.00%
上記成分1〜4に精製水を加えて全量を100g
とする。
例 4
(軟膏剤)
1 モノステアリン酸ポリオキシエチレングリコ
ール(40E.0.) 1.00%
2 自己乳化型モノステアリン酸グリセリン
0.50%
3 ステアリン酸 5.00%
4 ベヘニルアルコール 1.00%
5 流動パラフイン 10.00%
6 トリオクタン酸グリセリル 10.00%
7 パラオキシ安息香酸アステル 0.20%
8 1,3−ブチレングリコール 5.00%
*9 dl−α−トコフエロールリポソーム液
20.00%
10 エデト酸二ナトリウム 0.01%
11 コウジ酸 1.00%
12 香料 微量
上記成分1〜7を加温、溶解する。これに上記
成分8を精製水に加温、混合したものを加え乳
化、撹拌し、冷却する。これに上記成分9〜12を
加え撹拌混合する。かくして得られたものを冷却
後、容器に充填し、検査後製品とする。
(dl−α−トコフエロールリポソーム液の調製方
法)
1 dl−α−トコフエロール 1.00%
2 大豆リン脂質 4.00%
3 ポリエチレングリコール400 8.00%
4 エタノール 16.00%
上記成分1〜4に精製水を加えて、全量を100
gとし均一に撹拌混合する。
以上各実施例の%は全て重量%である。
次に本発明の外用剤の効果を試験例により説明
する。
1 本発明の外用剤の着色防止試験
1 試験方法
コウジ酸(K.A)1%溶液にビタミンE(V.E)
をそれぞれ0.005,0.05,0.1%(重量)になるよ
うに添加し、試料を調整した。
その時のV.Eはポリオキシエチレン硬化ヒマシ
油0.7%、エタノール0.5%、ポリエチレングリコ
ール400、15%の水溶液で可溶化したものを用い
た。
試験区
A KA1%水溶液V.Eは無添加、溶媒無添加(対
照)
B KA1% 〃 V.Eは0.1%添加
C KA1% 〃 V.Eは0.05%添加
D KA1% 〃 V.Eは0.005%添加
E KA1% 〃 V.Eは無添加、溶媒のみ(対
照)
各試験の試料を45℃で45日間放置し、それぞれ
0日、12日、29日、45日の420μmの着色(0D)
を測定した。
2 試験結果
下記表1の通りであつた。
[Industrial Application Field] The present invention relates to an external preparation having a melanin production inhibiting effect. [Prior art] So-called skin-lightening cosmetics that whiten human skin have long been used as cosmetics that contain peroxides such as hydrogen peroxide, magnesium peroxide, sodium peroxide, and zinc perborate. Ta. However, since these peroxides are extremely unstable substances, they have problems in storage stability and incorporation into cosmetic bases, and furthermore, their skin whitening effects have not been satisfactory. Recently, cosmetics containing vitamin C, cysteine, colloidal sulfur, etc. have been used for the purpose of fairing the skin, but the effects have not yet been sufficiently satisfactory. Furthermore, skin-lightening cosmetics using kojic acid (Japanese Patent Publication No. 56-18569), skin-lightening cosmetics containing derivatives of kojic acid (Japanese Patent Application Laid-open No. 56-79616, JP-A No. 56-7710, JP-A-Sho 56-7710,
59-33207, etc.) are known. In addition, fair skin cosmetics containing quercetin and flavonol compounds (JP-A-55-92305, JP-A-55-92305,
No. 111410, Japanese Patent Application Publication No. 111411, Japanese Patent Application Publication No. 1983-
143908, etc.) are known. On the other hand, vitamin E is a medicine used to treat habitual miscarriages, muscular atrophy, peripheral vascular disorders, heart diseases, etc., and is mainly used internally or as an oil solution injection. In addition, since it has a dilating effect on peripheral blood vessels, vitamin E is formulated into an ointment and marketed as a medicine for chilblains. Furthermore, in addition to the above-mentioned medicinal effects, vitamin E has a reducing effect and is therefore used as an antioxidant in cosmetics, pharmaceuticals, and the like. Furthermore, it is also disclosed that vitamin E is dissolved in water in the form of liposomes to make a whitening lotion and inhibit tyrosylose activity (Japanese Unexamined Patent Publication No. 1986-1999).
Publication No. 75421). [Problems to be solved by the invention] In the conventional technology, among the skin-lightening ingredients used in skin-lightening cosmetics, peroxide is a product that directly oxidizes and bleaches pigments such as melanin produced in the skin.
Excessive use bleaches the skin's original color, making the skin white, which is inconvenient. Moreover, kojic acid, furanobol, etc. suppress melanin production and are used as useful skin-whitening cosmetics. However, if this substance is stored for a long period of time, coloring may occur due to kojic acid. [Means for solving the problem] The present inventors have previously developed vitamin E or vitamin E
We researched the inhibition of melanin production by derivatives, and confirmed the surprising fact that although an aqueous solution of vitamin E does not inhibit tyrosinase activity, it has an extremely excellent melanin production inhibitory effect through tests using mouse melanoma-derived B16 cells. He invented a melanin production inhibiting topical drug containing E and/or its derivatives in a dissolved or suspended state, and filed an application as Japanese Patent Application No. 1983-246890. Recently, when kojic acid was added to a liquid containing the above-mentioned vitamin E and/or its derivatives in a dissolved or suspended state in the aqueous phase of a topical base, vitamin E and kojic acid had a synergistic effect that significantly inhibited melanin production. The present invention was completed based on the discovery that the external preparation containing kojic acid exhibits no coloring caused by long-term storage. The present invention is an external preparation for suppressing melanin production, which is characterized by containing an aqueous solution of kojic acid and/or a kojic acid derivative and an aqueous solution or suspension of vitamin E and/or a vitamin E derivative. The kojic acid derivative used in the present invention is 2-
Benzoyloxymethyl-5-hydroxy-4H
-pyran-4-one, 2-cinnamoyloxymethyl-5-hydroxy-4H-pyran-4-one,
2-phenoxymethyl-5-hydroxy-4H-
Includes pyran-4-one and the like. Vitamin E and vitamin E derivatives used in the present invention include natural vitamin E oil, vitamin E such as α-tocopherol, β-tocopherol, and γ-tocopherol, and vitamin E derivatives such as vitamin E acetate and vitamin E succinate, and their salts. included. External preparations are applied to the skin in the form of emulsions, ointments, pastes, poultices, lotions, etc. to suppress melanin produced in the skin, remove black and brown skin colors, and further inhibit melanin production. It is intended to prevent In order to dissolve the above-mentioned vitamin E and vitamin E derivatives alone or in a mixture of two or more thereof in the aqueous phase of the external drug, vitamin E and/or vitamin E derivatives are water-solubilized to form liposomes with phospholipids. Either make an aqueous solution by making vitamin E and/or a vitamin E derivative in water in the presence of a surfactant or a saponin vitamin E solubilizing agent such as Kyara saponin, or make vitamin E and/or a vitamin E derivative into an aqueous solution using an organic solution. It is dissolved in an organic solvent and mixed into the aqueous phase of an external preparation. In addition, even if the above-mentioned vitamin E and vitamin E derivatives do not completely dissolve in the aqueous phase and are partially suspended, if vitamin E etc. do not separate into the phase, they can be used as the external preparation of the present invention, and The effect can also be fully achieved. It may also be incorporated into the aqueous phase of an external preparation in a suspended state. In this case, surfactants, phospholipids, etc. are used as the suspending agent. When the above-mentioned vitamin E and/or vitamin E derivatives are water-solubilized, and when liposomes of vitamin E and vitamin E derivatives are formed, natural lecithin such as egg yolk lecithin, soybean lecithin, and distearoyl Vitamin E-containing liposomes are made using phospholipids of synthetic lecithin such as lecithin. The manufacturing method involves dissolving phospholipids and vitamin E in a solvent such as chloroform or benzene, distilling the solvent off under reduced pressure using a rotary evaporator, adding a buffer aqueous solution to the resulting thin film, and shaking it vigorously to swell it, forming a multilayer liposome. A method of producing monolamellar liposomes by producing phospholipids and irradiating them with ultrasonic waves. Phospholipids and vitamin E are dissolved in an organic solvent, and this solution is poured into an aqueous buffer solution being stirred to form liposomes. Method for producing phospholipids and vitamin E in chloroform,
A method of manufacturing liposomes by dissolving it in a solvent such as benzene, adding an aqueous buffer solution to it, emulsifying it into a water-in-oil type using ultrasound, distilling off the solvent using a rotary evaporator, and inverting the phase to an oil-in-water type using vortexing. It is manufactured by a known manufacturing method such as. When vitamin E and vitamin E derivatives are solubilized in water using a surfactant, a nonionic surfactant such as polyethylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyglycerin is used. Fatty acid ester, polyoxyethylene castor oil, polyoxyethylene phytosterol, polyoxyethylene lanolin derivative,
Anionic surfactants such as alkyl ether phosphoric acid such as polyoxyethylene alkyl ether and polyoxyethylene polyoxypropylene alkyl ether are used, and those having an HLB of 15 or more are preferred. Further, when ethanol, propylene glycol, etc. are added to the above-mentioned surfactant, the degree of solubilization is further improved. Further, in order to suspend vitamin E and vitamin E derivatives, the above-mentioned phospholipids, surfactants, etc. are added as suspending agents. The amount of kojic acid, kojic acid derivatives, vitamin E, and vitamin E derivatives used in the present invention to be contained in the external preparation is 0.1 to 0.1.
3.0% (weight), vitamin E, vitamin E derivatives
0.01-1.0% (by weight) is suitable. The external preparations of the present invention are mainly in the form of emulsions, ointments, pastes, poultices, lotions, etc. The above-mentioned kojic acid, kojic acid, etc. Derivatives, vitamin E, vitamin E derivatives 0.11 to 4.0% (weight)
Add it to make it a topical preparation. For example, in lotions, purified water is mixed with moisturizers such as glycerin and propylene glycol.
In the manufacture of general lotions, in which skin nutrients and the like are dissolved in alcohol, and the two are mixed and solubilized at room temperature, kojic acid, an aqueous solution of kojic acid derivatives, vitamin E,
A lotion is prepared by adding an aqueous solution or suspension of a vitamin E derivative to the above-mentioned content. In ointments, hydrophilic ingredients such as humectants such as glycerin and sorbitol are added to purified water to form the water phase, and the oil phase contains beeswax, paraffin, microcrystalline wax, ceresin, higher fatty acids, hydrogenated oil, etc. Oil components such as preservatives and surfactants are added to solid oils, semi-solid oils such as vaseline, lanolin, and glyceride, and liquid oils such as squalane, liquid paraffin, and various ester oils. The aqueous phase obtained in this way is heated,
In the general production of ointments by gradually adding an oil phase heated to the same temperature with gentle stirring and emulsifying it, an aqueous solution of kojic acid, kojic acid derivatives, vitamin E, and vitamin A are added to the aqueous phase. An aqueous solution or suspension of the E derivative is added to the above content to prepare an ointment. In emulsions, humectants such as glycerin, acid or alkaline PH adjusters, etc. are added to purified water, heated and mixed, and ethanol is added to form the aqueous phase, solid oils such as beeswax and paraffin, and semi-solids such as vaseline and lanolin are added. Add and adjust oily components such as preservatives and surfactants to liquid oils such as oil, squalane, liquid paraffin, and various ester oils, mix and heat to form an oil phase, and add the oil phase to the aqueous phase to prepare a reserve. In the production of general emulsions, in which a protective colloid such as carboxyvinyl polymer or carboxymethyl cellulose is added to the emulsified emulsifier, and the emulsion is uniformly emulsified using a homomixer, an aqueous solution of kojic acid or kojic acid derivatives is added to the aqueous phase. An emulsion is prepared by adding an aqueous solution or suspension of vitamin E or a vitamin E derivative to the above-mentioned content. For poultices, moisturizers such as glycerin, film agents such as polyvinyl alcohol, and vegum are added to purified water to swell it, and if necessary, powders such as kaolin, talc, and zinc oxide are added to add fragrance and preservatives. In the production of general poultices, in which ethanol in which the agent is dissolved is added and kneaded until it becomes a paste, an aqueous solution of kojic acid, a kojic acid derivative, and an aqueous solution or suspension of vitamin E, a vitamin E derivative, are added to the above-mentioned contents. Add as much as possible to make a poultice. [Example] Example 1 (Lotion agent) 1 Polyoxyethylene hydrogenated castor oil (60E.0)
1.00% 2 Flavoring trace amount 3 Ethanol 15.00% 4 Paraoxybenzoic acid ester 0.10% 5 Citric acid 0.10% 6 Sodium citrate 0.30% 7 1,3-Butylene glycol 4.00% *8 Natural vitamin E solubilized liquid 5.00% 9 Edetate di Sodium 0.01% 10 Kojic acid 0.50% Add purified water to the above ingredients 1 to 10, stir and dissolve uniformly, fill this into a container, and use it as a product after inspection. (Preparation method of natural vitamin E solution) 1. Natural vitamin E 1.00% 2. Polyoxyethylene hydrogenated castor oil (60E.0)
4.00% 3 Polyethylene glycol 400 8.00% 4 Ethanol 16.00% 5 Add purified water to bring the total amount to 100 g. Stir and mix the above components 1 to 5 uniformly. Example 2 (Poultice) 1 Polyvinyl alcohol 10.00% 2 Concentrated glycerin 2.00% 3 Ethanol 4.00% 4 Paraoxybenzoic acid ester 0.20% 5 Titanium oxide 2.00% 6 Kaolin 1.00% *7 Acetic acid dl-α-tocopherol solubilized liquid
10.00% 8 Disodium edetate 0.01% 9 Kojic acid 1.00% 10 Fragrance Trace amount Component 1 above is heated and dissolved in purified water, and Components 2, 4, 5, and 6 are added thereto, mixed, and cooled. Add components 3, 7, 8, 9, and 10 to this and stir and mix. After cooling, it is filled into a container and used as a product after inspection. (Preparation method of dl-α-tocopherol acetate solubilized solution) 1 dl-α-tocopherol acetate 1.00% 2 Polyoxyethylene castor oil (50E.0.)
4.00% 3 Polyethylene glycol 400 8.00% 4 Ethanol 16.00% Add purified water to the above ingredients to make a total amount of 100 g, and stir and mix uniformly. Example 3 (Emulsion) 1 Polyoxyethylene sorbitan monostearate (20E.0.) 1.00% 2 Polyoxyethylene sorbitan tetraoleate (60E.0) 0.50% 3 Lipophilic glyceryl monostearate 1.00% 4 Stearic acid 0.50% 5 Behenyl alcohol 0.50% 6 Avocado oil 4.00% 7 Glyceryl trioctanoate 4.00% 8 Paraoxybenzoic acid ester 0.20% 9 1,3-butylene glycol 5.00% 10 Xanthan gum 0.14% *11 Natural vitamin E liposome liquid 5.00% 12 Edetate di Sodium 0.01% 13 Kojic acid 1.00% 14 Flavor Small amount Add purified water to the above ingredients 1 to 14, fill in a container, and prepare the product. (Preparation method of natural vitamin E liposome liquid) 1. Natural vitamin E 1.00% 2. Egg yolk lecithin 4.00% 3. Poyethylene glycol 400 8.00% 4. Ethanol 16.00% Add purified water to the above ingredients 1 to 4 to make a total amount of 100 g
shall be. Example 4 (Ointment) 1 Polyoxyethylene glycol monostearate (40E.0.) 1.00% 2 Self-emulsifying glyceryl monostearate
0.50% 3 Stearic acid 5.00% 4 Behenyl alcohol 1.00% 5 Liquid paraffin 10.00% 6 Glyceryl trioctanoate 10.00% 7 Paraoxybenzoic acid aster 0.20% 8 1,3-Butylene glycol 5.00% *9 dl-α-tocopherol liposome solution
20.00% 10 Disodium edetate 0.01% 11 Kojic acid 1.00% 12 Fragrance Trace amount Heat and dissolve ingredients 1 to 7 above. A mixture of the above component 8 and purified water is added to the mixture, emulsified, stirred, and cooled. Add the above components 9 to 12 to this and mix with stirring. After cooling the product thus obtained, it is filled into a container and used as a product after inspection. (Preparation method of dl-α-tocopherol liposome solution) 1 dl-α-tocopherol 1.00% 2 Soybean phospholipid 4.00% 3 Polyethylene glycol 400 8.00% 4 Ethanol 16.00% Add purified water to the above ingredients 1 to 4 and prepare the total amount. 100
g and stir to mix evenly. All percentages in each example above are percentages by weight. Next, the effects of the external preparation of the present invention will be explained using test examples. 1 Coloration prevention test 1 of the external preparation of the present invention Test method Vitamin E (VE) in a 1% solution of kojic acid (KA)
were added to amounts of 0.005, 0.05, and 0.1% (by weight), respectively, to prepare samples. At that time, the VE used was one solubilized with an aqueous solution of 0.7% polyoxyethylene hydrogenated castor oil, 0.5% ethanol, and 15% polyethylene glycol 400. Test area A KA1% aqueous solution VE is not added, no solvent is added (control) B KA1% 〃 VE is added at 0.1% C KA1% 〃 VE is added at 0.05% D KA1% 〃 VE is added at 0.005% E KA1% 〃 VE is No additives, solvent only (control) Samples from each test were left at 45℃ for 45 days, and 420μm coloring (0D) on 0, 12, 29, and 45 days, respectively.
was measured. 2. Test results The results were as shown in Table 1 below.
本発明は上述の通り、従来公知のコウジ酸、コ
ウジ酸誘導体メラニン生成抑制効果とビタミンE
の効果が相乗的に作用した極めて優れたメラニン
生成抑制外用剤である。
As mentioned above, the present invention combines the conventionally known kojic acid, kojic acid derivative melanin production inhibiting effect, and vitamin E.
It is an extremely excellent melanin production suppressing topical agent with synergistic effects.
Claims (1)
とビタミンE及び/又はビタミンE誘導体の水溶
液又は懸濁液を含有することを特徴とするメラニ
ン生成抑制外用剤。1. An external preparation for suppressing melanin production, which contains an aqueous solution of kojic acid and/or a kojic acid derivative and an aqueous solution or suspension of vitamin E and/or a vitamin E derivative.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2058786A JPS62178506A (en) | 1986-02-01 | 1986-02-01 | Melanin formation suppressing external preparation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2058786A JPS62178506A (en) | 1986-02-01 | 1986-02-01 | Melanin formation suppressing external preparation |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS62178506A JPS62178506A (en) | 1987-08-05 |
JPS6324968B2 true JPS6324968B2 (en) | 1988-05-23 |
Family
ID=12031362
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2058786A Granted JPS62178506A (en) | 1986-02-01 | 1986-02-01 | Melanin formation suppressing external preparation |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS62178506A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1305268C (en) * | 2004-01-19 | 2007-03-14 | 英业达股份有限公司 | SOL realizing method accorded with IPMI standard |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2751965B2 (en) * | 1988-04-30 | 1998-05-18 | 川研ファインケミカル株式会社 | Cosmetics |
FR2664164A1 (en) * | 1990-07-04 | 1992-01-10 | Texinfine Patrinove | DERMATOLOGICAL OR COSMETIC COMPOSITION. |
JP3119491B2 (en) * | 1991-02-16 | 2000-12-18 | 三省製薬株式会社 | Topical melanin production inhibitor |
JP3566739B2 (en) * | 1993-09-30 | 2004-09-15 | 三省製薬株式会社 | Stabilization method for skin external preparation |
KR100422762B1 (en) * | 2001-12-05 | 2004-03-16 | 주식회사 태평양 | Kojic acid derivative and preparation method thereof |
TWI735652B (en) * | 2016-09-29 | 2021-08-11 | 心悅生醫股份有限公司 | Co-crystal and/or eutectic crystal of kojic acid, compositions comprising the same, and uses thereof |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS533538A (en) * | 1976-06-28 | 1978-01-13 | Sansho Seiyaku Kk | Skin bleach cosmetics |
JPS567776A (en) * | 1979-10-22 | 1981-01-27 | Sansho Seiyaku Kk | Diesterified compound of kojic acid |
JPS567710A (en) * | 1979-06-28 | 1981-01-27 | Sansho Seiyaku Kk | Whitening cosmetic |
JPS5618569A (en) * | 1979-07-24 | 1981-02-21 | Seiwa Kasei Kk | Color former for cattle meat |
JPS5675421A (en) * | 1979-11-22 | 1981-06-22 | Kanebo Keshohin Kk | Beautifying lotion |
JPS5679616A (en) * | 1979-12-05 | 1981-06-30 | Sansho Seiyaku Kk | Whitening cosmetic |
JPS56139409A (en) * | 1980-04-01 | 1981-10-30 | Kanebo Keshohin Kk | Whitening lotion |
JPS5770808A (en) * | 1980-10-20 | 1982-05-01 | Nonogawa Shoji:Kk | Production of emulsion for cosmetic |
JPS6051104A (en) * | 1983-08-30 | 1985-03-22 | Ajinomoto Co Inc | Vitamin e-containing aqueous solution |
-
1986
- 1986-02-01 JP JP2058786A patent/JPS62178506A/en active Granted
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS533538A (en) * | 1976-06-28 | 1978-01-13 | Sansho Seiyaku Kk | Skin bleach cosmetics |
JPS567710A (en) * | 1979-06-28 | 1981-01-27 | Sansho Seiyaku Kk | Whitening cosmetic |
JPS5618569A (en) * | 1979-07-24 | 1981-02-21 | Seiwa Kasei Kk | Color former for cattle meat |
JPS567776A (en) * | 1979-10-22 | 1981-01-27 | Sansho Seiyaku Kk | Diesterified compound of kojic acid |
JPS5675421A (en) * | 1979-11-22 | 1981-06-22 | Kanebo Keshohin Kk | Beautifying lotion |
JPS5679616A (en) * | 1979-12-05 | 1981-06-30 | Sansho Seiyaku Kk | Whitening cosmetic |
JPS56139409A (en) * | 1980-04-01 | 1981-10-30 | Kanebo Keshohin Kk | Whitening lotion |
JPS5770808A (en) * | 1980-10-20 | 1982-05-01 | Nonogawa Shoji:Kk | Production of emulsion for cosmetic |
JPS6051104A (en) * | 1983-08-30 | 1985-03-22 | Ajinomoto Co Inc | Vitamin e-containing aqueous solution |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1305268C (en) * | 2004-01-19 | 2007-03-14 | 英业达股份有限公司 | SOL realizing method accorded with IPMI standard |
Also Published As
Publication number | Publication date |
---|---|
JPS62178506A (en) | 1987-08-05 |
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