JP5177338B2 - L-ascorbic acid glucoside-containing liposome solution - Google Patents
L-ascorbic acid glucoside-containing liposome solution Download PDFInfo
- Publication number
- JP5177338B2 JP5177338B2 JP2005041504A JP2005041504A JP5177338B2 JP 5177338 B2 JP5177338 B2 JP 5177338B2 JP 2005041504 A JP2005041504 A JP 2005041504A JP 2005041504 A JP2005041504 A JP 2005041504A JP 5177338 B2 JP5177338 B2 JP 5177338B2
- Authority
- JP
- Japan
- Prior art keywords
- ascorbic acid
- liposome
- acid glucoside
- glucoside
- weight
- 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.)
- Active
Links
- 239000002502 liposome Substances 0.000 title claims description 115
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 title claims description 107
- 229960005070 ascorbic acid Drugs 0.000 title claims description 107
- 239000002211 L-ascorbic acid Substances 0.000 title claims description 98
- -1 L-ascorbic acid glucoside Chemical class 0.000 title claims description 89
- 235000000069 L-ascorbic acid Nutrition 0.000 title claims description 87
- 229930182478 glucoside Natural products 0.000 title claims description 86
- 150000003904 phospholipids Chemical class 0.000 claims description 40
- 239000002537 cosmetic Substances 0.000 claims description 33
- 230000002087 whitening effect Effects 0.000 claims description 26
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 25
- 125000002252 acyl group Chemical group 0.000 claims description 20
- 238000005538 encapsulation Methods 0.000 claims description 18
- 239000002245 particle Substances 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 239000007788 liquid Substances 0.000 claims description 10
- 235000021122 unsaturated fatty acids Nutrition 0.000 claims description 10
- 150000004670 unsaturated fatty acids Chemical class 0.000 claims description 10
- 239000006210 lotion Substances 0.000 claims description 7
- 150000005846 sugar alcohols Polymers 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- 238000000034 method Methods 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- 210000003491 skin Anatomy 0.000 description 16
- 239000012071 phase Substances 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 235000010323 ascorbic acid Nutrition 0.000 description 12
- 239000006185 dispersion Substances 0.000 description 11
- 238000002156 mixing Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 206010042496 Sunburn Diseases 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000011668 ascorbic acid Substances 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 9
- 238000002523 gelfiltration Methods 0.000 description 9
- 150000000996 L-ascorbic acids Chemical class 0.000 description 8
- 238000004040 coloring Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 8
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical class 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 7
- 235000020778 linoleic acid Nutrition 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 230000008099 melanin synthesis Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- 229940099578 hydrogenated soybean lecithin Drugs 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 239000000787 lecithin Substances 0.000 description 5
- 235000010445 lecithin Nutrition 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 241000700198 Cavia Species 0.000 description 4
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 4
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 4
- 208000003351 Melanosis Diseases 0.000 description 4
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 4
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000013329 compounding Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 4
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 4
- 229940067606 lecithin Drugs 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 230000035699 permeability Effects 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
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 4
- 229960000984 tocofersolan Drugs 0.000 description 4
- 206010014970 Ephelides Diseases 0.000 description 3
- 208000012641 Pigmentation disease Diseases 0.000 description 3
- 206010064127 Solar lentigo Diseases 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 229940049918 linoleate Drugs 0.000 description 3
- 230000019612 pigmentation Effects 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- BITHHVVYSMSWAG-KTKRTIGZSA-N (11Z)-icos-11-enoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCC(O)=O BITHHVVYSMSWAG-KTKRTIGZSA-N 0.000 description 2
- YWWVWXASSLXJHU-AATRIKPKSA-N (9E)-tetradecenoic acid Chemical compound CCCC\C=C\CCCCCCCC(O)=O YWWVWXASSLXJHU-AATRIKPKSA-N 0.000 description 2
- CUXYLFPMQMFGPL-UHFFFAOYSA-N (9Z,11E,13E)-9,11,13-Octadecatrienoic acid Natural products CCCCC=CC=CC=CCCCCCCCC(O)=O CUXYLFPMQMFGPL-UHFFFAOYSA-N 0.000 description 2
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 2
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 2
- 229940090949 docosahexaenoic acid Drugs 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 2
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 2
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229960004488 linolenic acid Drugs 0.000 description 2
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane 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
- 235000021313 oleic acid Nutrition 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 2
- 150000003905 phosphatidylinositols Chemical class 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000002904 solvent Substances 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
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical class CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 1
- IJTNSXPMYKJZPR-ZSCYQOFPSA-N (9Z,11E,13E,15Z)-octadecatetraenoic acid Chemical compound CC\C=C/C=C/C=C/C=C\CCCCCCCC(O)=O IJTNSXPMYKJZPR-ZSCYQOFPSA-N 0.000 description 1
- ZVRMGCSSSYZGSM-CCEZHUSRSA-N (E)-hexadec-2-enoic acid Chemical compound CCCCCCCCCCCCC\C=C\C(O)=O ZVRMGCSSSYZGSM-CCEZHUSRSA-N 0.000 description 1
- GCORITRBZMICMI-CMDGGOBGSA-N (e)-dodec-4-enoic acid Chemical compound CCCCCCC\C=C\CCC(O)=O GCORITRBZMICMI-CMDGGOBGSA-N 0.000 description 1
- RVUCYJXFCAVHNC-VAWYXSNFSA-N (e)-octadec-7-enoic acid Chemical compound CCCCCCCCCC\C=C\CCCCCC(O)=O RVUCYJXFCAVHNC-VAWYXSNFSA-N 0.000 description 1
- WRIDQFICGBMAFQ-ZHACJKMWSA-N (e)-octadec-8-enoic acid Chemical compound CCCCCCCCC\C=C\CCCCCCC(O)=O WRIDQFICGBMAFQ-ZHACJKMWSA-N 0.000 description 1
- WRIDQFICGBMAFQ-KHPPLWFESA-N (z)-octadec-8-enoic acid Chemical compound CCCCCCCCC\C=C/CCCCCCC(O)=O WRIDQFICGBMAFQ-KHPPLWFESA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- NNNVXFKZMRGJPM-ZHACJKMWSA-N 7-Palmitoleic acid Chemical compound CCCCCCCCC\C=C\CCCCC(O)=O NNNVXFKZMRGJPM-ZHACJKMWSA-N 0.000 description 1
- RVUCYJXFCAVHNC-QXMHVHEDSA-N 7Z-octadecenoic acid Chemical compound CCCCCCCCCC\C=C/CCCCCC(O)=O RVUCYJXFCAVHNC-QXMHVHEDSA-N 0.000 description 1
- YWWVWXASSLXJHU-UHFFFAOYSA-N 9E-tetradecenoic acid Natural products CCCCC=CCCCCCCCC(O)=O YWWVWXASSLXJHU-UHFFFAOYSA-N 0.000 description 1
- DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 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
- AHMIDUVKSGCHAU-UHFFFAOYSA-N Dopaquinone Natural products OC(=O)C(N)CC1=CC(=O)C(=O)C=C1 AHMIDUVKSGCHAU-UHFFFAOYSA-N 0.000 description 1
- NVTRPRFAWJGJAJ-UHFFFAOYSA-L EDTA monocalcium salt Chemical compound [Ca+2].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O NVTRPRFAWJGJAJ-UHFFFAOYSA-L 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000051366 Glycosyltransferases Human genes 0.000 description 1
- 108700023372 Glycosyltransferases Proteins 0.000 description 1
- AHMIDUVKSGCHAU-LURJTMIESA-N L-dopaquinone Chemical compound [O-]C(=O)[C@@H]([NH3+])CC1=CC(=O)C(=O)C=C1 AHMIDUVKSGCHAU-LURJTMIESA-N 0.000 description 1
- GCORITRBZMICMI-UHFFFAOYSA-N Linderic acid Natural products CCCCCCCC=CCCC(O)=O GCORITRBZMICMI-UHFFFAOYSA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 235000018330 Macadamia integrifolia Nutrition 0.000 description 1
- 240000000912 Macadamia tetraphylla Species 0.000 description 1
- 235000003800 Macadamia tetraphylla Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- CUXYLFPMQMFGPL-SUTYWZMXSA-N all-trans-octadeca-9,11,13-trienoic acid Chemical compound CCCC\C=C\C=C\C=C\CCCCCCCC(O)=O CUXYLFPMQMFGPL-SUTYWZMXSA-N 0.000 description 1
- CUXYLFPMQMFGPL-FWSDQLJQSA-N alpha-Eleostearic acid Natural products CCCCC=CC=C\C=C\CCCCCCCC(O)=O CUXYLFPMQMFGPL-FWSDQLJQSA-N 0.000 description 1
- IJTNSXPMYKJZPR-WVRBZULHSA-N alpha-parinaric acid Natural products CCC=C/C=C/C=C/C=CCCCCCCCC(=O)O IJTNSXPMYKJZPR-WVRBZULHSA-N 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000002585 base Substances 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
- 239000007844 bleaching agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- IXLCRBHDOFCYRY-UHFFFAOYSA-N dioxido(dioxo)chromium;mercury(2+) Chemical compound [Hg+2].[O-][Cr]([O-])(=O)=O IXLCRBHDOFCYRY-UHFFFAOYSA-N 0.000 description 1
- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960000735 docosanol Drugs 0.000 description 1
- GZZPOFFXKUVNSW-UHFFFAOYSA-N dodec-11-enoic acid Chemical compound OC(=O)CCCCCCCCCC=C GZZPOFFXKUVNSW-UHFFFAOYSA-N 0.000 description 1
- VJNCICVKUHKIIV-UHFFFAOYSA-N dopachrome Chemical compound O=C1C(=O)C=C2NC(C(=O)O)CC2=C1 VJNCICVKUHKIIV-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 229940108623 eicosenoic acid Drugs 0.000 description 1
- BITHHVVYSMSWAG-UHFFFAOYSA-N eicosenoic acid Natural products CCCCCCCCC=CCCCCCCCCCC(O)=O BITHHVVYSMSWAG-UHFFFAOYSA-N 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 235000021299 gondoic acid Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo 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
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- OYHQOLUKZRVURQ-AVQMFFATSA-N linoelaidic acid Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-AVQMFFATSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 239000010466 nut oil Substances 0.000 description 1
- SECPZKHBENQXJG-BQYQJAHWSA-N palmitelaidic acid Chemical compound CCCCCC\C=C\CCCCCCCC(O)=O SECPZKHBENQXJG-BQYQJAHWSA-N 0.000 description 1
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229940056692 resinol Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- PAWGRNGPMLVJQH-ZHACJKMWSA-N trans-2-dodecenoic acid Chemical compound CCCCCCCCC\C=C\C(O)=O PAWGRNGPMLVJQH-ZHACJKMWSA-N 0.000 description 1
- BITHHVVYSMSWAG-MDZDMXLPSA-N trans-gondoic acid Chemical compound CCCCCCCC\C=C\CCCCCCCCCC(O)=O BITHHVVYSMSWAG-MDZDMXLPSA-N 0.000 description 1
- IJTNSXPMYKJZPR-BYFNFPHLSA-N trans-parinaric acid Chemical compound CC\C=C\C=C\C=C\C=C\CCCCCCCC(O)=O IJTNSXPMYKJZPR-BYFNFPHLSA-N 0.000 description 1
- IJTNSXPMYKJZPR-UHFFFAOYSA-N trans-parinaric acid Natural products CCC=CC=CC=CC=CCCCCCCCC(O)=O IJTNSXPMYKJZPR-UHFFFAOYSA-N 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 239000006097 ultraviolet radiation absorber Substances 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
Landscapes
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、L−アスコルビン酸グルコシドを含有するリポソーム液に関し、さらに詳しくは、リポソーム中にL−アスコルビン酸グルコシドを内包する化粧料に関する。 The present invention relates to a liposome liquid containing L-ascorbic acid glucoside, and more particularly to a cosmetic containing L-ascorbic acid glucoside in the liposome.
リポソームは、脂質二分子膜から成り、その内部に水層を有する閉鎖小胞体であり、リポソームは広くバイオサイエンスの基礎、応用の分野で利用、検討されている。リポソームは生体膜と類似の成分であるリン脂質から構成されているため、細胞膜に結合しやすく、皮膚に塗布した場合、水分や種々の薬効成分を角質層に運搬できる。また、リポソーム中に内包されることによって、本来、不安定で失活しやすい薬効成分を長期間安定に保つことができる。 Liposomes are closed vesicles composed of a lipid bilayer membrane and an aqueous layer inside. Liposomes are widely used and studied in the fields of bioscience basics and applications. Liposomes are composed of phospholipids, which are components similar to biological membranes, so that they easily bind to cell membranes and can transport moisture and various medicinal ingredients to the stratum corneum when applied to the skin. In addition, by being encapsulated in liposomes, a medicinal component that is inherently unstable and easily deactivated can be kept stable for a long period of time.
アスコルビン酸及びその誘導体は、化粧料に美白剤として配合されている。L−アスコルビン酸(以下、「アスコルビン酸」と記載する)は、メラニン生成過程の代謝中間体であるドーパキノンからドーパクロムへの変換反応を抑制することで、メラニンの生成を抑制し、生成した有色の酸化型メラニンを無色の還元型メラニンに変換する作用を有しており、皮膚への美白効果、しみ、そばかす、黒皮症、肝班等の治療や改善に有効である。しかし、アスコルビン酸は化学的に不安定な化合物であるため、各種のアスコルビン酸誘導体が開発されている。特に各種アスコルビン酸誘導体の中でも、安定性、持続性、また化粧料への配合特性にも優れており、美白効果を有するL−アスコルビン酸グルコシドが注目されている。しかしながらアスコルビン酸誘導体によっては皮膚に対する即効的な浸透性がやや悪い場合もあり、化粧料に用いた場合、誘導体の種類によっては刺激性がある、水相と油相の相溶性に劣るものもあり、また配合成分やpHの影響により、経時的に着色を生じることもあり、さらに使いやすい化粧料が求められていた。例えばアスコルビン酸グルコシド、レシチンおよびキレート剤を用いた化粧料が開示されている(例えば特許文献1)。この化粧料はL−アスコルビン酸グルコシドのもつ持続性を保持したまま、経時的な着色の問題は改善されているものの、即時浸透性については満足な結果は得られなかった。特に、日焼けした後に衣服や水着等で覆われて日焼けしない部分と覆われていない部分で日焼けした部分との境目は色目が大きく異なり目立つため、後処理剤の開発が望まれていたのだが、従来の美白剤は日焼け部分も日焼けしていない部分も同様に美白してしまうため、境目がいつまでも残るものであった。
これらの問題点を解決するため、アスコルビン酸類を脂肪酸モノグリセリドからなるラメラ構造体に内包した皮膚外用剤が開示されている(例えば特許文献2)。更に、アスコルビン酸やその誘導体を含有するリポソームについて、これまで検討がなされてきた。例えばアスコルビン酸類をリン脂質リポソームに内包した美白化粧料が開示されている(例えば特許文献3)。また、臨界あるいは亜臨界状態の炭酸ガス、更に低級アルコール等の溶解剤を併用してアスコルビン酸類をリポソームに内包し、安定化する方法が開示されている(例えば特許文献4)。
しかし、特許文献3記載のものでは、日焼けの境目など局所的に美白効果を期待する場合、局所特異的な効果が得られにくく、処方自体の安定性が悪く、着色や臭気等に問題があるため、化粧品の配合処方が制限される等の問題があった。また、特許文献4記載のものでは、着色や臭気等が強く、化粧品の配合処方が制限されるなどの欠点があった。 However, in the thing of patent document 3, when a whitening effect is anticipated locally, such as the boundary of a sunburn, a local specific effect is hard to be obtained, the stability of prescription itself is bad, and there are problems with coloring, odor, etc. For this reason, there are problems such as restrictions on the formulation of cosmetics. Moreover, in the thing of patent document 4, coloring, odor, etc. were strong, and there existed a fault that the mixing | blending prescription of cosmetics was restrict | limited.
また、通常リポソームを製造する上で、グリセリン等の多価アルコールやエタノール等の有機溶剤を使用することがあるが、グリセリン等の多価アルコールが残存すると、べたつきの原因となり、使用上好ましくない場合があった。また、エタノール等の揮発性溶剤を使用した場合でも残存すると、配合上制限されるなどの問題があった。 Moreover, when manufacturing liposomes, polyhydric alcohols such as glycerin and organic solvents such as ethanol may be used. However, residual polyhydric alcohols such as glycerin may cause stickiness and are not preferable for use. was there. Moreover, even when a volatile solvent such as ethanol is used, if it remains, there is a problem that it is restricted in terms of formulation.
本発明は、より即時浸透性に優れ、美白効果が高く、また各種配合剤への配合特性に優れ、配合剤の影響による経時的に着色や臭いが生じにくく、種々の配合形態で使用できるL−アスコルビン酸グルコシド含有リポソーム液およびリポソーム含有化粧料を提供することを目的とする。 The present invention is more excellent in immediate permeability, high whitening effect, excellent in blending characteristics to various compounding agents, hardly colored or smelled over time due to the influence of the compounding agent, and can be used in various compounding forms. -It aims at providing the liposome liquid containing ascorbic-acid glucoside and liposome containing cosmetics.
すなわち本発明は、下記(1)〜(4)に掲げるL−アスコルビン酸グルコシド含有リポソーム液、(5)に掲げる美白用化粧料、および(6)に掲げるアフターサンローションである。
(1) リポソームを構成するリン脂質中のホスファチジルコリン含量が70重量%以上であり、リン脂質1重量部に対してL−アスコルビン酸グルコシドが0.1〜1重量部配合されているリポソーム液であって、前記リポソーム液に対してリン脂質の占める割合が0.1〜20重量%であり、L−アスコルビン酸グルコシドの内包率が50重量%以上であり、かつ前記リポソームの平均粒径が100〜800nmである、L−アスコルビン酸グルコシド含有リポソーム液。
(2) リポソームを構成するリン脂質中のホスファチジルコリン中のアシル基の不飽和脂肪酸の割合が70%以上である、請求項1記載のL−アスコルビン酸グルコシド含有リポソーム液。
(3) リポソームを構成するリン脂質中のホスファチジルコリン中のアシル基のリノール酸の割合が50%以上である、請求項1または2記載のL−アスコルビン酸グルコシド含有リポソーム液。
(4) リポソームの平均粒径が100〜300nmである請求項3記載のL−アスコルビン酸グルコシド含有リポソーム液。
(5) 請求項1〜4のいずれか1項に記載のL−アスコルビン酸グルコシド含有リポソーム液を50重量%以下含有する美白用化粧料。
(6) 請求項1〜4のいずれか1項に記載のL−アスコルビン酸グルコシド含有リポソーム液50重量%以下含有するアフターサンローション。
That is, the present invention is an L-ascorbic acid glucoside-containing liposome solution listed in (1) to (4) below, a whitening cosmetic listed in (5), and an after sun lotion listed in (6).
(1) A liposome solution in which the phosphatidylcholine content in the phospholipid constituting the liposome is 70% by weight or more and 0.1 to 1 part by weight of L-ascorbic acid glucoside is blended with 1 part by weight of phospholipid. The ratio of the phospholipid to the liposome liquid is 0.1 to 20% by weight, the encapsulation rate of L-ascorbic acid glucoside is 50% by weight or more, and the average particle size of the liposome is 100 to 100%. L-ascorbic acid glucoside-containing liposome solution which is 800 nm.
(2) The L-ascorbic acid glucoside-containing liposome solution according to claim 1, wherein the ratio of the unsaturated fatty acid of the acyl group in the phosphatidylcholine in the phospholipid constituting the liposome is 70% or more.
(3) The L-ascorbic acid glucoside-containing liposome solution according to claim 1 or 2, wherein the ratio of the linoleic acid of the acyl group in the phosphatidylcholine in the phospholipid constituting the liposome is 50% or more.
(4) The L-ascorbic acid glucoside-containing liposome solution according to claim 3, wherein the liposome has an average particle size of 100 to 300 nm.
(5) A whitening cosmetic comprising 50% by weight or less of the L-ascorbic acid glucoside-containing liposome solution according to any one of claims 1 to 4.
(6) An after-sun lotion containing 50% by weight or less of the L-ascorbic acid glucoside-containing liposome solution according to any one of claims 1 to 4.
本発明によれば、リポソーム中にアスコルビン酸誘導体を内包するリポソーム複合体を化粧料に含有することにより、アスコルビン酸誘導体の美白効果をより高めた、また経時的に着色や臭いが生じにくい化粧料を提供する。本発明は、L−アスコルビン酸グルコシドをリン脂質のホスファチジルコリン純度が高く、さらにリン脂質のアシル基の不飽和脂肪酸含有量の高い特定のリポソームに配合し、粒径を制御することにより、特に日焼け後の荒れた肌への浸透性が良好であるため、日焼け後の水着等のあとを残さないアフターサンローションへの適用がより効果的である。本発明は、日焼け後の皮膚への色素沈着やしみ、そばかす、肝班等の淡色改善効果に優れ、美白効果にも優れた化粧料を提供する。 According to the present invention, the cosmetic contains a liposome complex that encapsulates an ascorbic acid derivative in the liposome, thereby enhancing the whitening effect of the ascorbic acid derivative, and is less likely to cause coloration and odor over time. I will provide a. The present invention blends L-ascorbic acid glucoside with a specific liposome having a high phosphatidylcholine purity of phospholipid and a high unsaturated fatty acid content of phospholipid acyl group, and by controlling the particle size, particularly after sunburn. Since it has good permeability to rough skin, it is more effective to apply to after-sun lotion that does not leave behind a swimsuit after sunburn. The present invention provides a cosmetic that is excellent in light color improvement effects such as pigmentation and stains on the skin after sunburn, freckles, and liver spots, and also has an excellent whitening effect.
本発明のリポソームに内包されるL−アスコルビン酸グルコシドは、アスコルビン酸とグルコースを糖転移酵素により酵素反応にて生成された化合物である。具体例としては、α−D−グルコシル−L−アスコルビン酸である2−O−α−D−グルコシル−L−アスコルビン酸、5−O−α−D−グルコシル−L−アスコルビン酸、6−O−α−D−グルコシル−L−アスコルビン酸が安定性の点から優れており、特に好ましくは2−O−α−D−グルコシル−L−アスコルビン酸である。 The L-ascorbic acid glucoside encapsulated in the liposome of the present invention is a compound produced by enzymatic reaction of ascorbic acid and glucose with a glycosyltransferase. Specific examples include 2-O-α-D-glucosyl-L-ascorbic acid, which is α-D-glucosyl-L-ascorbic acid, 5-O-α-D-glucosyl-L-ascorbic acid, 6-O. -Α-D-glucosyl-L-ascorbic acid is excellent from the viewpoint of stability, and 2-O-α-D-glucosyl-L-ascorbic acid is particularly preferable.
本発明のL−アスコルビン酸グルコシド含有リポソーム液は、リン脂質とリポソームに内包させる水溶性物質を公知の技術により混合させることにより得られる。例えば、超音波処理法、フレンチプレス法、逆相蒸発法、界面活性剤法、エクストルージョン法、マントンゴーリン法、カルシウム−EDTAキレート法、凍結融解法、分散液を150MPa以上の圧力下でジェット流として噴射し、噴射口に対して配置された壁面に該ジェット流を衝突させて、上記ジェット流の方向と実質的に対向する方向に反転させる方法、増圧ポンプにより圧力波形がフラットで定圧に加圧された試料を超高圧でチャンバー内に入れ細管部を高速通過させ、強力な剪断力を受け、さらに合流部で加速された流体どうしが正面衝突することにより強い衝撃を受け、拡大部で圧力降下により強力なキャビテーションを受けることによって、リポソームを得る方法(マイクロフルイダイザー法)、真空乳化機を用いてリポソームを得る方法、高圧ホモミキサーを用いてリポソームを得る方法、等から目的に応じて選択することができる。 The L-ascorbic acid glucoside-containing liposome solution of the present invention can be obtained by mixing a phospholipid and a water-soluble substance encapsulated in the liposome by a known technique. For example, ultrasonic treatment method, French press method, reverse phase evaporation method, surfactant method, extrusion method, Manton Gorin method, calcium-EDTA chelate method, freezing and thawing method, and jetting a dispersion under a pressure of 150 MPa or more The jet flow collides with the wall surface arranged with respect to the injection port and is reversed in the direction substantially opposite to the jet flow direction. The pressurized sample is placed in the chamber under ultra-high pressure, passed through the narrow tube at high speed, and subjected to strong shearing force. Further, the fluid accelerated at the confluence receives a frontal impact and receives a strong impact. A method of obtaining liposomes by receiving strong cavitation due to pressure drop (microfluidizer method), using a vacuum emulsifier How to obtain the beam can be selected according to the purpose from a method of obtaining a liposome, or the like using a high pressure homomixer.
本発明のリポソームを構成するリン脂質は、分子内にリン酸基とアシル基及び/又はアルキル基からなる疎水基を2個以上有する化合物であり、例えば、ホスファチジルコリン(PC)、ホスファチジルエタノールアミン(PE)、ホスファチジルセリン(PS)、ホスファチジルイノシトール(PI)、ホスファチジルグリセロール(PG)、ホスファチジン酸(PA)、スフィンゴミエリン(SPM)、カルジオリピン、及びこれらの混合物である大豆レシチン、コーンレシチン、綿実油レシチン、卵黄レシチンなどの天然レシチンおよび水素添加大豆レシチン、水素添加卵黄レシチン、これらのリン脂質にポリエチレングリコールやアミノグリカン類を導入したリン脂質誘導体などが挙げられ、これらのうち、1種又は2種以上が混合して用いられる。 The phospholipid constituting the liposome of the present invention is a compound having two or more hydrophobic groups composed of a phosphate group and an acyl group and / or an alkyl group in the molecule, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE). ), Phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), sphingomyelin (SPM), cardiolipin, and mixtures thereof, soy lecithin, corn lecithin, cottonseed oil lecithin, egg yolk Natural lecithins such as lecithin and hydrogenated soybean lecithin, hydrogenated egg yolk lecithin, phospholipid derivatives in which polyethylene glycol or aminoglycan is introduced into these phospholipids, etc., of which one or more are mixed Used Te.
ここで、リポソームを構成するリン脂質中のホスファチジルコリン含量を70%以上とすることによって、L−アスコルビン酸グルコシド含有リポソームが安定的に調製でき、即時浸透性を付与することで、アスコルビン酸グルコシドの持つ美白効果をより一層高めることが可能となる。また、経時による着色や臭いが抑えられ、化粧品材料として汎用可能となるという点で産業上きわめて有用となる。リポソームを構成するリン脂質中のホスファチジルコリン含量が70%より少ないと、着色や臭いなどの問題があり、リポソームの安定性が悪くなるため、好ましくない。 Here, by setting the phosphatidylcholine content in the phospholipids constituting the liposome to 70% or more, the L-ascorbic acid glucoside-containing liposome can be stably prepared, and by imparting immediate permeability, the ascorbic acid glucoside has It is possible to further enhance the whitening effect. In addition, it is extremely useful industrially in that coloring and odor over time can be suppressed and it can be widely used as a cosmetic material. When the phosphatidylcholine content in the phospholipid constituting the liposome is less than 70%, there are problems such as coloring and odor, and the stability of the liposome is deteriorated.
本発明の前記観点からは、リポソームを構成するリン脂質中のホスファチジルコリン含量を75%以上とすることが更に好ましい。 From the said viewpoint of this invention, it is still more preferable that the phosphatidylcholine content in the phospholipid which comprises a liposome shall be 75% or more.
リン脂質中のホスファチジルコリンを構成するアシル基は、炭素数8〜22の不飽和脂肪酸の残基からなるアシル基であることが好ましく、例えば2-ラウロレイン酸、リンデル酸、トウハク酸、5-ラウロレイン酸、11-ラウロレイン酸、ツズ酸、5-ミリストレイン酸、ミリストレイン酸、2-パルミトレイン酸、7-パルミトレイン酸、cis-9-パルミトレイン酸、trans-9-パルミトレイン酸、ペトロセリン酸、ペトロセエライジン酸、cis-7-オクタデセン酸、trans-7-オクタデセン酸、cis-8-オクタデセン酸、trans-8-オクタデセン酸、オレイン酸、エライジン酸、バセニン酸、ゴンドイン酸、trans-ゴンドイン酸、エルシン酸、ブラシン酸、リノール酸、リノエライジン酸、α-エレオステアリン酸、β-エレオステアリン酸、リノレン酸、リノレンエライジン酸、プソイドエレオステアリン酸、α-パリナリン酸、β-パリナリン酸、アラキドン酸、エイコサペンタエン酸、ドコサヘキサエン酸等の直鎖不飽和カルボン酸由来のアシル基が挙げられ、好ましくはリノール酸、オレイン酸、リノレン酸、エイコサペンタエン酸、ドコサヘキサエン酸由来のアシル基である。 The acyl group constituting the phosphatidylcholine in the phospholipid is preferably an acyl group composed of a residue of an unsaturated fatty acid having 8 to 22 carbon atoms, such as 2-lauroleic acid, Linderic acid, succinic acid, and 5-laurolenic acid. , 11-lauroleic acid, tuzuic acid, 5-myristoleic acid, myristoleic acid, 2-palmitoleic acid, 7-palmitoleic acid, cis-9-palmitoleic acid, trans-9-palmitoleic acid, petroceric acid, petrocereidine Acid, cis-7-octadecenoic acid, trans-7-octadecenoic acid, cis-8-octadecenoic acid, trans-8-octadecenoic acid, oleic acid, elaidic acid, basenic acid, gondoic acid, trans-gondoic acid, erucic acid, Brassic acid, linoleic acid, linoelaidic acid, α-eleostearic acid, β-eleostearic acid, linolenic acid, linolenic elaidic acid, Psoi Examples include acyl groups derived from linear unsaturated carboxylic acids such as doereostearic acid, α-parinaric acid, β-parinaric acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, preferably linoleic acid, oleic acid, linolenic acid , An acyl group derived from eicosapentaenoic acid and docosahexaenoic acid.
特に、アシル基の中の不飽和脂肪酸含有率が70重量%以上であると、L−アスコルビン酸グルコシドの美白効果をより高めることができる。また、リノール酸含有率が50重量%以上であると、不飽和脂肪酸含有率が70重量%未満であっても、L−アスコルビン酸グルコシドの美白効果をより一層高めることができる。特に好ましくは、アシル基の中の不飽和脂肪酸含有率が70重量%以上であり、リノール酸含有率が50重量%以上である。 In particular, when the unsaturated fatty acid content in the acyl group is 70% by weight or more, the whitening effect of L-ascorbic acid glucoside can be further enhanced. Further, when the linoleic acid content is 50% by weight or more, the whitening effect of L-ascorbic acid glucoside can be further enhanced even when the unsaturated fatty acid content is less than 70% by weight. Particularly preferably, the unsaturated fatty acid content in the acyl group is 70% by weight or more, and the linoleic acid content is 50% by weight or more.
本発明のL−アスコルビン酸グルコシド含有リポソーム液の中に占めるリン脂質の割合は、0.1〜20重量%が好ましく、また、リン脂質とL−アスコルビン酸グルコシドとの配合比は、美白効果や保存時の安定性等の面から、リン脂質1重量部に対し、L−アスコルビン酸グルコシド0.1〜1重量部が好ましい。リン脂質1重量部に対し、L−アスコルビン酸グルコシドが0.1重量部より少ないと美白効果が充分ではなく、1重量部より多くなるとリポソームの調製が困難となる。 The proportion of phospholipid in the L-ascorbic acid glucoside-containing liposome solution of the present invention is preferably 0.1 to 20% by weight, and the blending ratio of phospholipid and L-ascorbic acid glucoside is a whitening effect or From the viewpoint of stability during storage and the like, 0.1 to 1 part by weight of L-ascorbic acid glucoside is preferable with respect to 1 part by weight of phospholipid. If the amount of L-ascorbic acid glucoside is less than 0.1 part by weight relative to 1 part by weight of the phospholipid, the whitening effect is not sufficient, and if it exceeds 1 part by weight, preparation of the liposome becomes difficult.
本発明のリポソームの平均粒径は100〜800nmであることが望ましく、より好ましくは100〜300nmが望ましい。平均粒径が100nmより小さくなると、L−アスコルビン酸グルコシドを充分にリポソーム中に含有できず、リポソームの美白効果を充分に得られなくなり、800nmより大きくなると、皮膚からの吸収率が悪くなり、リポソームの美白効果を充分に得られなくなる。また、リポソームが相分離や凝集を起こし易く、保存中又は皮膚滞留中に不安定となる。 The average particle size of the liposome of the present invention is preferably 100 to 800 nm, more preferably 100 to 300 nm. When the average particle size is smaller than 100 nm, L-ascorbic acid glucoside cannot be sufficiently contained in the liposome, and the whitening effect of the liposome cannot be sufficiently obtained. When the average particle size is larger than 800 nm, the absorption rate from the skin is deteriorated. The whitening effect cannot be obtained sufficiently. Liposomes are prone to phase separation and aggregation, and become unstable during storage or skin retention.
本発明のリポソームにおけるL−アスコルビン酸グルコシドの配合比はリン脂質1重量部に対して0.1〜1重量部が好ましいが、さらにこの時配合したL−アスコルビン酸グルコシドがリポソーム内に内包される内包率は50重量%以上であることが望ましい。ここでいう内包率とは、リポソーム液に含有されるL−アスコルビン酸グルコシドの総量に対して、リポソームの中に内包されたL−アスコルビン酸グルコシドの割合を意味する。例えば、リン脂質1重量部に対し、0.6重量部のL−アスコルビン酸グルコシドを配合した時、0.6重量部のL−アスコルビン酸グルコシドのうち0.3重量部以上のL−アスコルビン酸グルコシドがリポソームに内包されていることが望ましい。この内包率は、ゲルろ過カラムを用いてリポソームに内包されなかったL−アスコルビン酸グルコシドを分離除去した後、メタノールとクロロホルムおよび水とを加えて、リン脂質をクロロホルムにL−アスコルビン酸グルコシドをメタノール、水混液に抽出して定量を行うことにより求めることができる。また、L−アスコルビン酸グルコシドは逆相カラムを用いたHPLC法(UV検出波長240nm)により定量することができる。リポソームへのL−アスコルビン酸グルコシドの内包率が50重量%以上より少なくなると、日焼けした皮膚に対する美白効果が薄くなり、日焼けした部分と日焼けしていない部分の境目が消えにくくなるので、好ましくない。 The mixing ratio of L-ascorbic acid glucoside in the liposome of the present invention is preferably 0.1 to 1 part by weight with respect to 1 part by weight of phospholipid, and the L-ascorbic acid glucoside compounded at this time is encapsulated in the liposome. The encapsulation rate is desirably 50% by weight or more. The encapsulation rate here means the ratio of L-ascorbic acid glucoside encapsulated in the liposome with respect to the total amount of L-ascorbic acid glucoside contained in the liposome liquid. For example, when 0.6 part by weight of L-ascorbic acid glucoside is blended with 1 part by weight of phospholipid, 0.3 part by weight or more of L-ascorbic acid glucoside out of 0.6 part by weight of L-ascorbic acid glucoside. It is desirable that the glucoside is encapsulated in the liposome. This encapsulation rate was determined by separating and removing L-ascorbic acid glucoside that was not encapsulated in liposomes using a gel filtration column, adding methanol, chloroform and water, and adding phospholipid to chloroform and L-ascorbic acid glucoside to methanol. It can be obtained by extracting into a water mixture and performing quantification. Moreover, L-ascorbic acid glucoside can be quantified by HPLC method (UV detection wavelength 240 nm) using a reverse phase column. If the encapsulation rate of L-ascorbic acid glucoside in the liposome is less than 50% by weight or more, the whitening effect on the tanned skin is diminished, and the boundary between the tanned part and the non-tanned part becomes difficult to disappear.
本発明のリポソームを構成するリン脂質中のホスファチジルコリン含量は70%以上であり、リン脂質の相転移温度以上の温度で製造を行うことにより、2種以上のリン脂質を混合する場合においても製造工程には有機溶剤を使用せずに均一で安定なリポソームを得ることができる。そのため、有機溶剤除去工程が不必要であり、工業的には極めて有利である。また製造されたリポソームが有機溶剤等の余分な配合物を含まないため、配合の自由度が大きいものである。本発明のリポソームは(A)リン脂質0.1〜20重量%に対して、水80〜99.9重量%を加え、リン脂質の相転移温度以上の温度で乳化させる工程、(B)L−アスコルビン酸グルコシド水溶液と(A)で得られた乳化液とを混合する工程から製造することができる。 The phosphatidylcholine content in the phospholipid constituting the liposome of the present invention is 70% or more, and the production process is performed even when two or more phospholipids are mixed by producing at a temperature higher than the phase transition temperature of the phospholipid. Can obtain a uniform and stable liposome without using an organic solvent. Therefore, the organic solvent removal step is unnecessary and industrially very advantageous. Moreover, since the manufactured liposome does not contain an extra compound such as an organic solvent, the degree of freedom of compounding is large. The liposome of the present invention comprises (A) a step of adding 80 to 99.9% by weight of water to 0.1 to 20% by weight of phospholipid and emulsifying at a temperature equal to or higher than the phase transition temperature of phospholipid, (B) L -It can manufacture from the process of mixing the ascorbic-acid glucoside aqueous solution and the emulsion obtained by (A).
本発明のリポソームを、既存の製剤に混合することで、化粧料を調製することが出来る。含有させる方法としては、製剤の最終段階で混合しても良く、製剤の途中、例えば、水相を添加する際に、混合しても良い。混合条件は、通常の化粧料を製造する条件がそのまま適用できる。本発明によるリポソーム中にL−アスコルビン酸グルコシドを内包するリポソームは、既存の製剤に混合してもリポソームが安定に保たれ、L−アスコルビン酸グルコシドの安定性が損なわれることがない。 Cosmetics can be prepared by mixing the liposome of the present invention with an existing preparation. As a method of inclusion, they may be mixed at the final stage of the preparation, or may be mixed during the preparation, for example, when an aqueous phase is added. As the mixing conditions, the conditions for producing ordinary cosmetics can be applied as they are. The liposome encapsulating L-ascorbic acid glucoside in the liposome according to the present invention can be stably maintained even when mixed with an existing preparation, and the stability of L-ascorbic acid glucoside is not impaired.
なお、本発明のリポソーム液を含有する化粧料には、化粧料に常用されている添加剤として、アルコール、水性基剤、油性基剤、界面活性剤、顔料、色素、pH調製剤、防腐剤、殺菌剤、キレート剤、抗酸化剤、紫外線吸収剤、動植物由来の天然エキス、香料、無機塩等を本発明の性能を損なわない範囲で配合することも可能である。 In addition, in cosmetics containing the liposome liquid of the present invention, alcohols, aqueous bases, oily bases, surfactants, pigments, dyes, pH adjusters, preservatives are commonly used additives for cosmetics. In addition, a bactericidal agent, a chelating agent, an antioxidant, an ultraviolet absorber, natural extracts derived from animals and plants, fragrances, inorganic salts and the like can be blended within a range that does not impair the performance of the present invention.
本発明で本リポソーム液が配合できる化粧料の剤形は、医薬品、医薬部外品及び化粧品に通常用いられる剤形、すなわち剤形としては、液状、ゲル状、ペースト状、クリーム状などの形態に適用可能である。 The cosmetic dosage form to which the present liposome liquid can be incorporated in the present invention is a dosage form usually used for pharmaceuticals, quasi drugs and cosmetics, that is, the dosage form is in the form of liquid, gel, paste, cream, etc. It is applicable to.
さらに本リポソーム液を凍結乾燥、噴霧乾燥などの公知の手段により水分を除去した後に配合することによって、粉末状あるいは固状などの形態に適用可能であり、これらの形態に特に限定されるものではない。本発明は、このように請求項1〜4のいずれか一つの請求項に記載のリポソーム液を乾燥して得られた粉体をも提供する。この粉体においては、リポソームを構成するリン脂質中のホスファチジルコリン含量が70重量%以上であり、リン脂質1重量部に対してL−アスコルビン酸グルコシドが0.1〜1重量部配合されており、リポソームの平均粒径が100〜800nmである。好ましくは、リポソームを構成するリン脂質中のホスファチジルコリン中のアシル基の不飽和脂肪酸の割合が70%以上であり、および/または、リポソームを構成するリン脂質中のホスファチジルコリン中のアシル基のリノール酸の割合が50%以上であり、および/または、リポソームの平均粒径が100〜300nmである。 Furthermore, the present liposome solution can be applied to a powdery or solid form by mixing after removing water by known means such as freeze-drying and spray-drying, and is not particularly limited to these forms. Absent. Thus, the present invention also provides a powder obtained by drying the liposome liquid according to any one of claims 1 to 4. In this powder, the phosphatidylcholine content in the phospholipid constituting the liposome is 70% by weight or more, and 0.1 to 1 part by weight of L-ascorbic acid glucoside is blended with respect to 1 part by weight of the phospholipid. The average particle size of the liposome is 100 to 800 nm. Preferably, the ratio of the unsaturated fatty acid of the acyl group in the phosphatidylcholine in the phospholipid constituting the liposome is 70% or more, and / or the linoleic acid of the acyl group in the phosphatidylcholine in the phospholipid constituting the liposome The ratio is 50% or more, and / or the average particle size of the liposome is 100 to 300 nm.
本発明は、L−アスコルビン酸グルコシドをリン脂質のホスファチジルコリン純度が高く、リン脂質のアシル基の不飽和脂肪酸含有量の高い特定のリポソーム処方に配合し、さらに粒径を制御することにより、特に日焼け後の荒れた肌への浸透性が良好であり、日焼けしていない、荒れていない肌へは浸透しにくいリポソーム処方としているため、日焼け後の水着等のあとを残さないアフターサンローションへの適用がより効果的である。本発明により、日焼け後の皮膚への色素沈着やしみ、そばかす、肝班等の淡色改善効果に優れ、美白効果にも優れた化粧料を提供することができる。 The present invention includes L-ascorbic acid glucoside in a specific liposome formulation having a high phosphatidylcholine purity of phospholipids and a high unsaturated fatty acid content of phospholipid acyl groups, and further controlling the particle size, thereby tanning in particular. Since it is a liposome formulation that has good penetration into rough skin afterwards and is not tanned or difficult to penetrate into rough skin, it can be applied to after-sun lotions that do not leave behind after sunburn. Is more effective. According to the present invention, it is possible to provide a cosmetic that is excellent in light color improvement effects such as pigmentation and stains on the skin after sunburn, freckles, and liver spots, and also has an excellent whitening effect.
以下、実施例に基づき本発明を更に詳しく説明する。
(実施例1)
[L−アスコルビン酸グルコシド内包リポソームの調製]
精製水84.9gに未水素添加大豆レシチン(日本油脂(株)製、COATSOME NC−20)10g(ホスファチジルコリン純度92.6%、不飽和アシル基含有量80.5%、このうちリノール酸アシル基65.2%、脂肪酸組成の詳細は表1を参照)、L−アスコルビン酸グルコシド(2−O−α−D−グルコシル−L−アスコルビン酸)5g、dl−α−トコフェロール0.1gを添加し、ポリトロン(キネマティカ製、ロータ・ステータ式ホモジナイザー)を用い回転数20,000rpm、室温で10分間攪拌し、脂質含有粗分散液を調製した。この脂質含有粗分散液をDeBEE2000(ビーイーイーインターナショナル製、超高圧乳化分散破砕機)にて、圧力10,000psiで5回微粒子化処理を施し、L−アスコルビン酸グルコシド内包リポソーム(粒径183nm)を得た。このとき、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率はゲルろ過法により測定した結果、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率は80%であった。
Hereinafter, the present invention will be described in more detail based on examples.
Example 1
[Preparation of liposome containing L-ascorbic acid glucoside]
84.9 g of purified water and 10 g of unhydrogenated soybean lecithin (COATSOME NC-20, manufactured by NOF Corporation) (phosphatidylcholine purity 92.6%, unsaturated acyl group content 80.5%, of which linoleate acyl group 65.2%, see Table 1 for details of fatty acid composition), 5 g of L-ascorbic acid glucoside (2-O-α-D-glucosyl-L-ascorbic acid), 0.1 g of dl-α-tocopherol Using a Polytron (manufactured by Kinematica, rotor-stator type homogenizer), the mixture was stirred at room temperature for 10 minutes at 20,000 rpm to prepare a lipid-containing crude dispersion. This lipid-containing crude dispersion was subjected to micronization treatment 5 times at a pressure of 10,000 psi using DeBEE2000 (manufactured by BEE International Co., Ltd., ultra-high pressure emulsification dispersion crusher) to give L-ascorbic acid glucoside-encapsulated liposomes (particle size: 183 nm). Obtained. At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 80%.
ここで、内包率の測定方法について説明する。ゲルろ過カラム(担体:ファルマシア、セファデックスG50;カラム直径16mm;カラム高さ300mm)を通してリポソーム複合体をゲルろ過し、溶出液を分画した(2.5mL/分画)。各分画より0.8mLを採取し、メタノール2mLを加えて攪拌した後、クロロホルム1mLを加えて攪拌し、いったん全体を透明に溶解させた。これにクロロホルム1mLを加えて攪拌し、更に蒸留水1.2mLを加えて攪拌後、冷却遠心分離機(久保田商事(株)製KR−702型)にて遠心分離(3,500rpm、10分間、室温)し、分離した二層の上層(水及びメタノール相)に回収されるL−アスコルビン酸グルコシド量を高速液体クロマトグラフィーにより測定した(カラム:和光純薬工業、Wakosik-II 5C18 HG 4.6mm×250nm、カラム温度:35℃、移動相:0.02M リン酸二水素カリウム(2.722g/L)-水(pH2.0)、流速:1.0mL/min)。 Here, a method for measuring the encapsulation rate will be described. The liposome complex was subjected to gel filtration through a gel filtration column (carrier: Pharmacia, Sephadex G50; column diameter 16 mm; column height 300 mm), and the eluate was fractionated (2.5 mL / fraction). 0.8 mL was collected from each fraction, 2 mL of methanol was added and stirred, then 1 mL of chloroform was added and stirred, and the whole was once dissolved transparently. Chloroform (3500 rpm, 10 minutes) was added to 1 mL of chloroform and stirred, 1.2 mL of distilled water was further added thereto, and the mixture was stirred and cooled with a cooling centrifuge (model KR-702 manufactured by Kubota Corporation). Room temperature), and the amount of L-ascorbic acid glucoside recovered in the separated upper two layers (water and methanol phase) was measured by high performance liquid chromatography (column: Wako Pure Chemical Industries, Wakosik-II 5C18 HG 4.6 mm × 250 nm, column temperature: 35 ° C., mobile phase: 0.02 M potassium dihydrogen phosphate (2.722 g / L) -water (pH 2.0), flow rate: 1.0 mL / min).
(実施例2)
[L−アスコルビン酸グルコシド内包リポソームの調製]
水素添加大豆レシチン(日本油脂(株)製、COATSOME NC−61)10g(ホスファチジルコリン純度75.3%、不飽和アシル基なし、このうちリノール酸アシル基なし、脂肪酸組成の詳細は表2参照)を用いて、実施例1と同様の方法でリポソームを調製した(粒径220nm)。このとき、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率はゲルろ過法により測定した結果、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率は75%であった。
(Example 2)
[Preparation of liposome containing L-ascorbic acid glucoside]
Hydrogenated soybean lecithin (manufactured by NOF Corporation, COATSOME NC-61) 10 g (phosphatidylcholine purity 75.3%, no unsaturated acyl group, no linoleate acyl group, see Table 2 for details of fatty acid composition) The liposomes were prepared in the same manner as in Example 1 (particle size: 220 nm). At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 75%.
(実施例3)
[L−アスコルビン酸グルコシド内包リポソームの調製]
水素添加大豆レシチン(日本油脂(株)製、COATSOME NC−21)10g(ホスファチジルコリン純度95.1%、不飽和アシル基なし、リノール酸アシル基なし)にジエチルエーテル/エタノール混合溶液(9/1、v/v)1000mlを加え溶解した後、水を200ml添加し、マグネチックスターラーで攪拌後、ソニケーターで超音波処理を30分間行った。その後、ロータリーエバポレーターでジエチルエーテルおよびエタノールを留去し、濃度調整後エクストルーダーを用いてポリカーボネート製のフィルター(孔径0.6μm)で濾過してリポソームを調製した(粒径504nm)。このとき、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率はゲルろ過法により測定した結果、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率は78%であった。
(Example 3)
[Preparation of liposome containing L-ascorbic acid glucoside]
Hydrogenated soybean lecithin (Nippon Yushi Co., Ltd., COATSOME NC-21) 10 g (phosphatidylcholine purity 95.1%, no unsaturated acyl group, no linoleic acid acyl group) in diethyl ether / ethanol mixed solution (9/1, v / v) After adding 1000 ml and dissolving, 200 ml of water was added, stirred with a magnetic stirrer, and then subjected to ultrasonic treatment with a sonicator for 30 minutes. Thereafter, diethyl ether and ethanol were distilled off with a rotary evaporator, and after adjusting the concentration, the mixture was filtered through a polycarbonate filter (pore size 0.6 μm) to prepare liposomes (particle size 504 nm). At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 78%.
(比較例1)
精製水95gにL−アスコルビン酸グルコシド(2−O−α−D−グルコシル−L−アスコルビン酸)5g加え、マグネティックスターラーにて攪拌し、溶解させた。
(Comparative Example 1)
5 g of L-ascorbic acid glucoside (2-O-α-D-glucosyl-L-ascorbic acid) was added to 95 g of purified water, and the mixture was stirred and dissolved with a magnetic stirrer.
(比較例2)
[L−アスコルビン酸グルコシド内包リポソーム複合体の調製]
精製水79.9gに水素添加大豆レシチン(日本油脂(株)製、COATSOME NC−21)10g(ホスファチジルコリン純度95.1%、不飽和アシル基なし、リノール酸アシル基なし)、dl−α−トコフェロール0.1gを添加し、ポリトロン(キネマティカ製、ロータ・ステータ式ホモジナイザー)を用い回転数20,000rpm、室温で10分間攪拌し、脂質含有粗分散液を調製した。この脂質含有粗分散液をDeBEE2000(ビーイーイーインターナショナル製、超高圧乳化分散破砕機)にて、圧力10,000psiで5回微粒子化処理を施し、L−アスコルビン酸グルコシドを含まない空のリポソームを得た。そこへ、L−アスコルビン酸グルコシド(2−O−α−D−グルコシル−L−アスコルビン酸)5gを添加し、マグネチックスターラーで30分間攪拌した。このときのリポソームの粒径は247nmであった。また、リポソーム中のL−アスコルビン酸グルコシドの内包率はゲルろ過法により測定した結果、1%であった。
(Comparative Example 2)
[Preparation of L-ascorbic acid glucoside-encapsulating liposome complex]
79.9 g of purified water, 10 g of hydrogenated soybean lecithin (manufactured by NOF Corporation, COATSOME NC-21) (phosphatidylcholine purity 95.1%, no unsaturated acyl group, no linoleic acid acyl group), dl-α-tocopherol 0.1 g was added, and the mixture was stirred for 10 minutes at room temperature using a Polytron (manufactured by Kinematica, rotor-stator type homogenizer) at a rotation speed of 20,000 rpm to prepare a lipid-containing coarse dispersion. This lipid-containing crude dispersion is subjected to microparticulation treatment 5 times at a pressure of 10,000 psi using DeBEE2000 (manufactured by BEE International Co., Ltd.) to obtain empty liposomes that do not contain L-ascorbic acid glucoside. It was. Thereto, 5 g of L-ascorbic acid glucoside (2-O-α-D-glucosyl-L-ascorbic acid) was added and stirred with a magnetic stirrer for 30 minutes. The particle size of the liposome at this time was 247 nm. Further, the encapsulation rate of L-ascorbic acid glucoside in the liposome was 1% as a result of measurement by gel filtration.
(比較例3)
[L−アスコルビン酸グルコシド内包リポソーム複合体の調製]
精製水79.9gに水素添加大豆レシチン(日光ケミカルズ製、レシノールS−10)10g(ホスファチジルコリン純度31.8%、不飽和アシル基なし、リノール酸アシル基なし)、L−アスコルビン酸グルコシド(2−O−α−D−グルコシル−L−アスコルビン酸)5g、dl−α−トコフェロール0.1gを添加し、ポリトロン(キネマティカ製、ロータ・ステータ式ホモジナイザー)を用い回転数20,000rpm、室温で10分間攪拌し、脂質含有粗分散液を調製した。この脂質含有粗分散液をDeBEE2000(ビーイーイーインターナショナル製、超高圧乳化分散破砕機)にて、圧力10,000psiで5回微粒子化処理を施し、L−アスコルビン酸グルコシド内包リポソーム(粒径161nm)を得た。このとき、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率はゲルろ過法により測定した結果、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率は68%であった。
(Comparative Example 3)
[Preparation of L-ascorbic acid glucoside-encapsulating liposome complex]
79.9 g of purified water, 10 g of hydrogenated soybean lecithin (manufactured by Nikko Chemicals, Resinol S-10) (phosphatidylcholine purity 31.8%, no unsaturated acyl group, no linoleic acid acyl group), L-ascorbic acid glucoside (2- 5 g of O-α-D-glucosyl-L-ascorbic acid) and 0.1 g of dl-α-tocopherol were added, and using a polytron (manufactured by Kinematica, rotor-stator homogenizer) at a rotation speed of 20,000 rpm for 10 minutes at room temperature. Stirring to prepare a lipid-containing crude dispersion. This lipid-containing crude dispersion was subjected to micronization treatment at a pressure of 10,000 psi with DeBEE2000 (produced by BEE International Co., Ltd., ultra-high pressure emulsification dispersion crusher) to give L-ascorbic acid glucoside-encapsulated liposomes (particle size: 161 nm). Obtained. At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 68%.
(比較例4)
[L−アスコルビン酸グルコシド内包リポソーム複合体の調製]
精製水79.9gに未水素添加大豆レシチン(日本油脂(株)製、COATSOME NC−20)10g(ホスファチジルコリン純度92.6%、不飽和アシル基含有量80.5%、このうちリノール酸アシル基65.2%)、L−アスコルビン酸グルコシド(2−O−α−D−グルコシル−L−アスコルビン酸)5g、dl−α−トコフェロール0.1gを添加し、ポリトロン(キネマティカ製、ロータ・ステータ式ホモジナイザー)を用い回転数20,000rpm、室温で10分間攪拌し、脂質含有粗分散液を調製した(粒径604nm)。このとき、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率はゲルろ過法により測定した結果、L−アスコルビン酸グルコシドを内包するリポソーム中のL−アスコルビン酸グルコシドの内包率は16%であった。
(Comparative Example 4)
[Preparation of L-ascorbic acid glucoside-encapsulating liposome complex]
79.9 g of purified water and 10 g of unhydrogenated soybean lecithin (manufactured by NOF Corporation, COATSOME NC-20) (phosphatidylcholine purity 92.6%, unsaturated acyl group content 80.5%, of which linoleate acyl group 65.2%), 5 g of L-ascorbic acid glucoside (2-O-α-D-glucosyl-L-ascorbic acid) and 0.1 g of dl-α-tocopherol were added, and Polytron (manufactured by Kinematica, rotor-stator type) The mixture was stirred at room temperature for 10 minutes using a homogenizer to prepare a lipid-containing crude dispersion (particle size: 604 nm). At this time, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured by gel filtration. As a result, the encapsulation rate of L-ascorbic acid glucoside in the liposome encapsulating L-ascorbic acid glucoside was measured. Was 16%.
(実施例1〜3および比較例1〜4)
(化粧料の評価)
上記実施例および比較例で得たL−アスコルビン酸グルコシド含有リポソーム分散液を使用して表3に示す化粧水である化粧料を調製した。調製方法はプロペラミキサーを用いた。但し、添加成分として表3に示す4成分を共通添加成分として使用した。
(1)モルモットを用いたメラニン生成抑制効果
褐色モルモットを用いてin
vivoにおけるメラニン生成抑制効果の評価を行った。すなわち、褐色モルモットの背部を剃毛し、5×10cmの長方形の穴を開けた紫外線遮蔽版で覆い、紫外線を照射した(0.5J/cm2)。色素沈着が形成された後、表1の化粧料50μLを1日2回塗布した。そして、塗布前と塗布後20日後及び40日後の黒化の度合いを色差計(ミノルタ製、分光測色計CM−2600d)にて測定した。結果を表3に示す。
(Examples 1-3 and Comparative Examples 1-4)
(Evaluation of cosmetics)
Using the L-ascorbic acid glucoside-containing liposome dispersion liquid obtained in the above Examples and Comparative Examples, cosmetics as skin lotions shown in Table 3 were prepared. The preparation method used a propeller mixer. However, four components shown in Table 3 were used as additive components as common additive components.
(1) Inhibition of melanin production using guinea pigs in brown guinea pigs
The melanin production inhibitory effect in vivo was evaluated. That is, the back of a brown guinea pig was shaved, covered with an ultraviolet shielding plate having a rectangular hole of 5 × 10 cm, and irradiated with ultraviolet rays (0.5 J / cm 2 ). After the pigmentation was formed, 50 μL of the cosmetic material shown in Table 1 was applied twice a day. Then, the degree of blackening before application and after 20 days and 40 days after application was measured with a color difference meter (manufactured by Minolta, spectrocolorimeter CM-2600d). The results are shown in Table 3.
(2)美白効果
20名の女性(25才〜40才)をパネラーとし、1日朝晩2回ずつ2ヶ月間、表3の化粧料を使用し、その後の皮膚の「シミ」、「ソバカス」の改善度を肉眼で下記のように判定し、20名の平均値を求めて、平均値7点以上を美白効果の高い皮膚外用剤であると評価した。結果を表3に示す。
10点:明らかに有効であると判断された場合。
5点:やや効果が有ると判断された場合。
0点:全く効果が無いと判断された場合。
(2) Whitening effect 20 females (25 to 40 years old) are panelists and use the cosmetics shown in Table 3 twice a day for two months each day, followed by “spots” and “sobacas” on the skin. The degree of improvement was determined with the naked eye as follows, the average value of 20 people was obtained, and an average value of 7 or more was evaluated as a skin external preparation with a high whitening effect. The results are shown in Table 3.
10 points: When clearly determined to be effective.
5 points: When judged to have some effect.
0 point: When it is judged that there is no effect at all.
20名の女性(25才〜40才)をパネラーとし、右腕上腕部に絆創膏を貼付し、夏の海岸で4時間日光浴を行った後、絆創膏をはがし、1日朝晩2回ずつ5日間、表3の化粧料を絆創膏のはがした部分に塗布した。絆創膏のはがした部分のきわ部分について、日焼けあとの改善度を肉眼で下記のように判定した。
○:日焼けあとが目立たない
×:日焼けあとが残っている
20 women (25 to 40 years old) are panelists, apply adhesive bandages to the upper arm of their right arm, sunbathe on the summer beach for 4 hours, peel off the adhesive bandages, and take up the morning twice a day for 5 days. 3 cosmetics were applied to the peeled part of the bandage. The degree of improvement after sunburn was determined with the naked eye as follows for the wrinkled part of the peeled part of the adhesive bandage.
○: After sunburn is inconspicuous ×: After sunburn remains
(3)経時安定性(着色度合い)
化粧料を透明ガラス容器に密封して0℃、25℃および40℃で3ヶ月間保存し、その外観を観察して、下に示す3段階で評価した。結果を表4に示す。
○:安定性良好(いずれの温度でも外観の変化がない。)
△:安定性やや不良(いずれかの温度において、やや着色を生じる。)
×:安定性不良(いずれかの温度においてより、着色を生じる。)
(3) Stability over time (degree of coloring)
The cosmetic was sealed in a transparent glass container and stored at 0 ° C., 25 ° C. and 40 ° C. for 3 months. The appearance was observed and evaluated in the following three stages. The results are shown in Table 4.
○: Good stability (no change in appearance at any temperature)
Δ: Slightly inferior (slightly colored at any temperature)
X: Stability failure (coloring occurs at any temperature)
(4)経時安定性(におい)
化粧料を透明ガラス容器に密封して0℃、25℃および40℃で3ヶ月間保存し、そのにおいを20名の女性(25才〜40才)をパネラーとし、下に示す2段階で評価した。結果を表3に示す。
○:20名中4名以下のパネラーがにおいが強くなっていると感じた。
×:20名中5名以上のパネラーがにおいが強くなっていると感じた。
(4) Stability over time (odor)
The cosmetic is sealed in a transparent glass container and stored at 0 ° C, 25 ° C and 40 ° C for 3 months, and its odor is evaluated in two stages as shown below with 20 women (25 to 40 years old) as panelists. did. The results are shown in Table 3.
○: Fewer than 4 panelists out of 20 felt that the smell was strong.
X: More than 5 panelists out of 20 felt that the smell was strong.
(5)経時安定性(沈殿度合い)
化粧料を透明ガラス容器に密封して0℃、25℃および40℃で3ヶ月間保存し、その外観を観察して、下に示す2段階で評価した。結果を表4に示す。
○:安定性良好(いずれの温度でも外観の変化がない。)
×:安定性不良(いずれかの温度においており、沈殿を生じるまたは分離する。)
(5) Stability over time (degree of precipitation)
The cosmetic was sealed in a transparent glass container and stored at 0 ° C., 25 ° C. and 40 ° C. for 3 months. The appearance was observed and evaluated in the following two stages. The results are shown in Table 4.
○: Good stability (no change in appearance at any temperature)
X: Stability failure (at any temperature, causing precipitation or separation)
注1;2−O−α−D−グルコシル−L−アスコルビン酸((株)林原生物化学研究所製)
注2;ΔL*:色差計のL*値(明度)で、照射前を0としてUV照射後のL*値との差を黒化度とした。すなわち、値の低い方が黒化度は高い。
Note 1: 2-O-α-D-glucosyl-L-ascorbic acid (manufactured by Hayashibara Biochemical Research Institute)
Note 2; ΔL *: L * value (brightness) of a color difference meter, where 0 is before irradiation and the difference from L * value after UV irradiation is blackness. That is, the lower the value, the higher the degree of blackening.
表3、表4より、本発明の化粧水である化粧料(実施例1〜3)は比較例1〜4と比較して褐色モルモットのメラニン生成を顕著に抑制することが判り、いずれも美白効果に優れるとともに、経時安定性にも優れていた。一方、比較例1〜4では、これらの効果すべてにおいて十分な性能が得られていない。つまり、比較例1〜4ではL−アスコルビン酸グルコシドをリン脂質のホスファチジルコリン純度が高く、リン脂質のアシル基の不飽和脂肪酸含有量が高い特定のリポソーム処方に配合し、さらに粒径を制御していないため、美白効果および経時安定性の双方を満足する十分な性能が得られていない。 From Tables 3 and 4, it can be seen that the cosmetics (Examples 1 to 3), which are the skin lotions of the present invention, markedly suppress melanin production in brown guinea pigs as compared with Comparative Examples 1 to 4, both of which are whitening. The effect was excellent and the stability over time was also excellent. On the other hand, in Comparative Examples 1-4, sufficient performance is not obtained in all of these effects. That is, in Comparative Examples 1 to 4, L-ascorbic acid glucoside is blended in a specific liposome formulation having high phosphatidylcholine purity of phospholipid and high unsaturated fatty acid content of acyl group of phospholipid, and further controlling the particle size. Therefore, sufficient performance satisfying both the whitening effect and the temporal stability is not obtained.
(実施例4)
(エモリエントクリーム)
(処方)
油相 重量%
モノステアリン酸ポリオキシエチレン40 2.0
自己乳化型モノステアリン酸グリセリル 5.0
ステアリン酸 2.0
セタノール 2.0
スクワラン 12.0
マカデミアナッツ油 4.0
メチルポリシロキサン 0.2
防腐剤 適量
水相
1,3−ブタンジオール 7.0
精製水 残部
リポソーム
実施例3のリポソーム 50.0
Example 4
(Emollient cream)
(Prescription)
Oil phase wt%
Polyoxyethylene monostearate 40 2.0
Self-emulsifying glyceryl monostearate 5.0
Stearic acid 2.0
Cetanol 2.0
Squalane 12.0
Macadamia nut oil 4.0
Methylpolysiloxane 0.2
Preservative Appropriate amount of water phase 1,3-butanediol 7.0
Purified water Residual liposomes Example 3 liposomes 50.0
(調製法)
油相、水相ともに80℃で加温溶解し、水相を油相に攪拌しながら徐々に加えて乳化する。更に攪拌を続けて冷却し、40℃以下でリポソームを添加、更に攪拌して均一混合した。
(Preparation method)
Both the oil phase and the aqueous phase are dissolved by heating at 80 ° C., and the aqueous phase is gradually added to the oil phase while stirring to emulsify. Furthermore, stirring was continued and the mixture was cooled, liposomes were added at 40 ° C. or lower, and further stirred to mix uniformly.
(実施例5)
乳液
(処方)
油相 重量%
モノステアリン酸ポリオキシエチレン20ソルビタン 1.0
テトラオレイン酸ポリオキシエチレン40ソルビトール 0.5
モノステアリン酸ソルビタン 1.0
ステアリン酸 0.5
ベヘニルアルコール 0.5
ミツロウ 0.5
スクワラン 10.0
トリイソオクタン酸グリセリル 10.0
デカオレイン酸デカグリセリル 3.0
1,3−ブタンジオール 7.0
防腐剤 適量
水相
キサンタンガム 0.04
トリエタノールアミン 0.05
精製水 残部
リポソーム
実施例3のリポソーム 50.0
(調製法)
実施例4の方法に従って調製した。
(Example 5)
Latex (prescription)
Oil phase wt%
Polyoxyethylene 20 sorbitan monostearate 1.0
Tetraoleic acid polyoxyethylene 40 sorbitol 0.5
Sorbitan monostearate 1.0
Stearic acid 0.5
Behenyl alcohol 0.5
Beeslow 0.5
Squalane 10.0
Glyceryl triisooctanoate 10.0
Decaoleic acid decaglyceryl 3.0
1,3-butanediol 7.0
Preservative Appropriate amount of water phase Xanthan gum 0.04
Triethanolamine 0.05
Purified water Residual liposomes Example 3 liposomes 50.0
(Preparation method)
Prepared according to the method of Example 4.
これら実施例4〜5について、実施例1〜3と同様に(1)モルモットを用いたメラニン生成抑制効果、および(2)美白効果の試験を行った。試験結果を表5に示す。 About these Examples 4-5, the test of (1) melanin production inhibitory effect using a guinea pig and (2) whitening effect was done like Examples 1-3. The test results are shown in Table 5.
表5の結果からわかるように、実施例4および実施例5では、褐色モルモットのメラニン生成を顕著に抑制し、いずれも美白効果に優れる効果が認められた。
As can be seen from the results in Table 5, in Example 4 and Example 5, melanin production in brown guinea pigs was remarkably suppressed, and both were excellent in whitening effect.
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2005041504A JP5177338B2 (en) | 2005-02-18 | 2005-02-18 | L-ascorbic acid glucoside-containing liposome solution |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2005041504A JP5177338B2 (en) | 2005-02-18 | 2005-02-18 | L-ascorbic acid glucoside-containing liposome solution |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2006225327A JP2006225327A (en) | 2006-08-31 |
JP5177338B2 true JP5177338B2 (en) | 2013-04-03 |
Family
ID=36987008
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2005041504A Active JP5177338B2 (en) | 2005-02-18 | 2005-02-18 | L-ascorbic acid glucoside-containing liposome solution |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP5177338B2 (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2912054B1 (en) * | 2007-02-06 | 2009-05-15 | Idenov Lab | COSMETIC COMPOSITION COMPRISING AN ASSOCIATION OF THREE FORMS OF VITAMIN C |
US20110171288A1 (en) * | 2008-02-20 | 2011-07-14 | Fatemeh Mohammadi | Topical compositions and methods for whitening skin |
MX2012002696A (en) | 2009-09-03 | 2012-08-15 | Hayashibara Biochem Lab | Powder containing anhydrous crystals of 2-o-î -d-glucosyl-l-ascor bic acid, manufacturing method therefor, and use thereof. |
WO2012033218A1 (en) | 2010-09-07 | 2012-03-15 | 株式会社林原生物化学研究所 | HYDROUS CRYSTALS OF 2-O-α-D-GLUCOSYL-L-ASCORBIC ACID, POWDER CONTAINING HYDROUS CRYSTALS OF 2-O-α-D-GLUCOSYL-L-ASCORBIC ACID, METHOD FOR PRODUCING THE HYDROUS CRYSTALS, METHOD FOR PRODUCING THE POWDER, USE OF THE HYDROUS CRYSTALS, AND USE OF THE POWDER |
JP2012158570A (en) * | 2011-02-02 | 2012-08-23 | Mikimoto Pharmaceut Co Ltd | Emulsion |
MY165639A (en) | 2011-03-07 | 2018-04-18 | Hayashibara Co | A process for producing a particulate composition comprising anhydrous crystalline 2-o-alpha-d-glucosyl-l-ascorbic |
JP6051015B2 (en) * | 2012-10-30 | 2016-12-21 | ポーラ化成工業株式会社 | Vesicle-dispersed aqueous solution and composition for external use on skin containing the vesicle-dispersed aqueous solution |
IL274753B (en) * | 2020-05-18 | 2021-06-30 | Bionext Labs Ltd | Antiviral compositions comprising liposome-encapsulated ascorbyl glucoside and natural extracts |
CN111557912B (en) * | 2020-06-04 | 2021-07-27 | 江南大学 | Preparation method of fatty acid-based VC liposome |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004059496A (en) * | 2002-07-29 | 2004-02-26 | Q P Corp | Cosmetic |
WO2004076602A1 (en) * | 2003-02-27 | 2004-09-10 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Method of preventing lipids constituting lipid membrane from degradation and use thereof |
-
2005
- 2005-02-18 JP JP2005041504A patent/JP5177338B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
JP2006225327A (en) | 2006-08-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5177338B2 (en) | L-ascorbic acid glucoside-containing liposome solution | |
JP3687277B2 (en) | Whitening cosmetics | |
EP1327434B1 (en) | Nanoemulsion comprising metabolites of ginseng saponin and a skin-care composition for anti-aging containing the same | |
EP2727580B1 (en) | Astaxanthin-containing composition, method for manufacturing same, and cosmetic | |
KR101052493B1 (en) | Blessicle dispersions and cosmetics containing the same | |
US8541010B2 (en) | Cosmetic composition comprising double-shell nano-structure | |
JP2003119120A (en) | Method for producing liposome, cosmetic containing the liposome, and skin care preparation | |
JPWO2006118246A1 (en) | Transdermal absorption enhancer | |
KR102177196B1 (en) | Nanoparticle multi-layered lamellar niosomes which is formed by nanoparticlation after being formed large niosomes in a supercritical state and cosmetic composition thereof | |
KR100949848B1 (en) | Nanoemulsion composition comprising Vitamin-C derivative and method for preparing thereof | |
JP2017088604A (en) | Transparent face lotion | |
JPWO2006118245A1 (en) | Skin regeneration promoter | |
KR20140096040A (en) | Aqueous dispersion and method for producing same | |
JP2007153801A (en) | Humectant and cosmetic containing the same | |
JP2008074780A (en) | Method for controlling skin absorption part of liposome, and controlled release agent of liposome skin absorption | |
JP2009062288A (en) | Percutaneous absorption controller containing sophorolipid and method for producing the same | |
WO2013125708A1 (en) | Topical skin preparation and healthy skin cell activation agent | |
JP2006131567A (en) | Method for producing liposome suspension and application using liposome | |
KR102339804B1 (en) | Manufacturing method for more enhancing stability by encapsulating active ingredients in a liposome structure formed as a multilayer in a molecular clustering state, and a cosmetic composition containing the same | |
JP2005179313A (en) | Method for producing base agent for skin cosmetic, and skin cosmetic | |
KR101910962B1 (en) | Ceramide liquid crystal composition and Preparation Method Thereof | |
KR20180000828A (en) | Cosmetic composition containing cordycepin stabilized by solid lipid nanoparticles | |
KR101929932B1 (en) | Cosmetic composition of skin moisture and manufacturing method thereof | |
Kang et al. | Effects of liquid crystal-based formulation on transdermal delivery of retinyl palmitate and proliferation of epidermal cells | |
KR101607166B1 (en) | Whitening cosmetic composition containing liposomes comprising phosphatidyl ethanolamine and phosphatidyl choline |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080214 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110519 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20110705 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20110714 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110719 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20110706 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20110714 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120221 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20121211 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A712 Effective date: 20121218 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20121225 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5177338 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |