JP4712300B2 - Whitening agent and vitamin mixture composition - Google Patents
Whitening agent and vitamin mixture composition Download PDFInfo
- Publication number
- JP4712300B2 JP4712300B2 JP2003420438A JP2003420438A JP4712300B2 JP 4712300 B2 JP4712300 B2 JP 4712300B2 JP 2003420438 A JP2003420438 A JP 2003420438A JP 2003420438 A JP2003420438 A JP 2003420438A JP 4712300 B2 JP4712300 B2 JP 4712300B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- test
- riboflavin
- calcium pantothenate
- whitening agent
- 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 - Lifetime
Links
- 239000000203 mixture Substances 0.000 title description 40
- 230000002087 whitening effect Effects 0.000 title description 30
- 239000003795 chemical substances by application Substances 0.000 title description 26
- 229940088594 vitamin Drugs 0.000 title description 18
- 229930003231 vitamin Natural products 0.000 title description 18
- 235000013343 vitamin Nutrition 0.000 title description 18
- 239000011782 vitamin Substances 0.000 title description 18
- 150000003722 vitamin derivatives Chemical class 0.000 title description 17
- 239000004480 active ingredient Substances 0.000 claims description 8
- 239000007844 bleaching agent Substances 0.000 claims description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 52
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 41
- 238000012360 testing method Methods 0.000 description 34
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 27
- 229960002079 calcium pantothenate Drugs 0.000 description 27
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 26
- 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 26
- 229960002477 riboflavin Drugs 0.000 description 26
- 235000019192 riboflavin Nutrition 0.000 description 26
- 239000002151 riboflavin Substances 0.000 description 26
- 210000002752 melanocyte Anatomy 0.000 description 25
- 235000005152 nicotinamide Nutrition 0.000 description 21
- 239000011570 nicotinamide Substances 0.000 description 21
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 21
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 21
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 21
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 20
- 239000007788 liquid Substances 0.000 description 14
- 229960003966 nicotinamide Drugs 0.000 description 14
- 230000035882 stress Effects 0.000 description 14
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 12
- 210000003491 skin Anatomy 0.000 description 12
- 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 11
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 11
- 208000012641 Pigmentation disease Diseases 0.000 description 11
- 239000000049 pigment Substances 0.000 description 11
- 239000000600 sorbitol Substances 0.000 description 11
- 230000019612 pigmentation Effects 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 8
- 102400000739 Corticotropin Human genes 0.000 description 8
- 101800000414 Corticotropin Proteins 0.000 description 8
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 8
- 229960000258 corticotropin Drugs 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 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 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000010998 test method Methods 0.000 description 6
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 5
- 229930003268 Vitamin C Natural products 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 235000019154 vitamin C Nutrition 0.000 description 5
- 239000011718 vitamin C Substances 0.000 description 5
- 230000037303 wrinkles Effects 0.000 description 5
- 206010051246 Photodermatosis Diseases 0.000 description 4
- 230000032683 aging Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 210000005069 ears Anatomy 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- -1 lipid peroxide Chemical class 0.000 description 4
- 230000008845 photoaging Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 206010014970 Ephelides Diseases 0.000 description 3
- 241000219051 Fagopyrum Species 0.000 description 3
- 235000009419 Fagopyrum esculentum Nutrition 0.000 description 3
- 208000003351 Melanosis Diseases 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 229930003427 Vitamin E Natural products 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
- 239000013068 control sample Substances 0.000 description 3
- 210000001339 epidermal cell Anatomy 0.000 description 3
- 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 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000013074 reference sample Substances 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- LBIBJGZCAVJMOV-UHFFFAOYSA-N 4,5-bis(hydroxymethyl)-2-methylpyridin-3-ol pyridine-3-carboxamide hydrochloride Chemical compound Cl.NC(=O)c1cccnc1.Cc1ncc(CO)c(CO)c1O LBIBJGZCAVJMOV-UHFFFAOYSA-N 0.000 description 2
- 238000001061 Dunnett's test Methods 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 description 2
- 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 description 2
- 102400000740 Melanocyte-stimulating hormone alpha Human genes 0.000 description 2
- 101710200814 Melanotropin alpha Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000004376 Sucralose Substances 0.000 description 2
- 241000425571 Trepanes Species 0.000 description 2
- 102000003425 Tyrosinase Human genes 0.000 description 2
- 108060008724 Tyrosinase Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 229960000271 arbutin Drugs 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000000481 effect on pigmentation Effects 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- 239000008274 jelly Substances 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 2
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 2
- 229960004705 kojic acid Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 210000004694 pigment cell Anatomy 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 229940029079 rose petal extract Drugs 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000009759 skin aging Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 2
- 235000019408 sucralose Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WHNFPRLDDSXQCL-UAZQEYIDSA-N α-msh Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H](CO)NC(C)=O)C1=CC=C(O)C=C1 WHNFPRLDDSXQCL-UAZQEYIDSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 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 1
- AEDORKVKMIVLBW-BLDDREHASA-N 3-oxo-3-[[(2r,3s,4s,5r,6r)-3,4,5-trihydroxy-6-[[5-hydroxy-4-(hydroxymethyl)-6-methylpyridin-3-yl]methoxy]oxan-2-yl]methoxy]propanoic acid Chemical compound OCC1=C(O)C(C)=NC=C1CO[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](COC(=O)CC(O)=O)O1 AEDORKVKMIVLBW-BLDDREHASA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- AFSDNFLWKVMVRB-UHFFFAOYSA-N Ellagic acid Chemical compound OC1=C(O)C(OC2=O)=C3C4=C2C=C(O)C(O)=C4OC(=O)C3=C1 AFSDNFLWKVMVRB-UHFFFAOYSA-N 0.000 description 1
- ATJXMQHAMYVHRX-CPCISQLKSA-N Ellagic acid Natural products OC1=C(O)[C@H]2OC(=O)c3cc(O)c(O)c4OC(=O)C(=C1)[C@H]2c34 ATJXMQHAMYVHRX-CPCISQLKSA-N 0.000 description 1
- 229920002079 Ellagic acid Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108010063907 Glutathione Reductase Proteins 0.000 description 1
- 102100036442 Glutathione reductase, mitochondrial Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 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
- 206010027145 Melanocytic naevus Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000006750 UV protection Effects 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 208000007047 blue nevus Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000004177 elastic tissue Anatomy 0.000 description 1
- 229960002852 ellagic acid Drugs 0.000 description 1
- 235000004132 ellagic acid Nutrition 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 125000000687 hydroquinonyl group Chemical class C1(O)=C(C=C(O)C=C1)* 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 235000021056 liquid food Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000008099 melanin synthesis Effects 0.000 description 1
- 210000002780 melanosome Anatomy 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- FAARLWTXUUQFSN-UHFFFAOYSA-N methylellagic acid Natural products O1C(=O)C2=CC(O)=C(O)C3=C2C2=C1C(OC)=C(O)C=C2C(=O)O3 FAARLWTXUUQFSN-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Description
本発明は、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤及びそれらからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物に関する。 The present invention is characterized by containing a whitening agent containing as an active ingredient at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate, and at least three selected from the group consisting thereof. Relates to a vitamin mixture composition.
美容上の観点から、シミやソバカスに悩んでいる人が多い。シミやソバカスあるいはクスミやシワといった肌の老化は、紫外線照射、酸化的刺激、ホルモン異常、遺伝的要素などに大きく影響を受けていると言われており、その中でも紫外線照射の影響が最も大きいと考えられている。皮膚表面上で紫外線を受けると、組織内でフリーラジカル（活性酸素）が発生し、この活性酸素によって、細胞損傷や炎症が惹起されると、炎症系のケミカル・メディエーターを介して、色素沈着を惹起すると言われている。 Many people suffer from spots and freckles from a cosmetic point of view. It is said that skin aging such as spots, buckwheat or kusumi or wrinkles is greatly influenced by ultraviolet irradiation, oxidative stimulation, hormonal abnormalities, genetic factors, etc. It is considered. When exposed to ultraviolet rays on the skin surface, free radicals (active oxygen) are generated in the tissue, and when this active oxygen causes cell damage or inflammation, pigmentation occurs via an inflammatory chemical mediator. It is said to provoke.
また紫外線照射などの影響により、メラノサイト刺激ホルモン（α−ＭＳＨ）や副腎皮質刺激ホルモン（ＡＣＴＨ）など複数のメラノサイト活性化因子の分泌が促進され、色素沈着を誘発することも知られている。 It is also known that secretion of a plurality of melanocyte activators such as melanocyte stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH) is promoted by the influence of ultraviolet irradiation and the like, and pigmentation is induced.
また、現代社会で増え続けるストレスによってもメラノサイト刺激ホルモン（α−ＭＳＨ）や副腎皮質刺激ホルモン（ＡＣＴＨ）など複数のメラノサイト活性化因子の分泌が促進され、色素沈着を誘発することも知られており、ストレス環境下で紫外線を浴びることは、色素沈着が顕著に強くなり、難治性のシミやソバカスが生じやすくなる。 In addition, it is known that stress that continues to increase in modern society also promotes the secretion of multiple melanocyte activators such as melanocyte stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH), and induces pigmentation. When exposed to ultraviolet rays in a stress environment, pigmentation becomes remarkably strong, and intractable spots and freckles tend to occur.
一方、色素沈着の生成は本来、生体防御反応の一つと考えられている。すなわち、皮膚表面細胞上で遺伝情報であるＤＮＡを紫外線照射などから防御するために、表皮細胞に存在する色素細胞（メラノサイト）内のメラノソームと呼ばれるメラニン生成顆粒においてメラニン色素が産生される。このようにして生成したメラニン色素が隣接する細胞に拡散し、表皮細胞のケラチノサイトに蓄積され、皮膚の新陳代謝によりケラチノサイトは通常角質層となり、やがて皮膚から剥がれ落ちると考えられているが、必要以上に過剰にメラニン色素が産生された場合には、表皮内や真皮層に沈着して、その結果、シミとなって残存すると考えられている。 On the other hand, the formation of pigmentation is originally considered as one of the biological defense reactions. That is, melanin pigments are produced in melanin-producing granules called melanosomes in pigment cells (melanocytes) present in epidermal cells in order to protect DNA, which is genetic information, from ultraviolet irradiation and the like on skin surface cells. The melanin pigment produced in this way diffuses to adjacent cells and accumulates in keratinocytes of epidermal cells, and it is thought that keratinocytes usually become the stratum corneum due to metabolism of the skin, and eventually peel off from the skin. When excessive melanin pigment is produced, it is considered that it deposits in the epidermis or dermis layer, and as a result, remains as a spot.
そして上記のメラニン色素は大きく分けて色の濃いユウメラニンと淡色のフェオメラニンの２種類があり、いずれも紫外線の防御に寄与すること、また紫外線照射時にはユウメラニン合成が活性化されることも知られている。 The above melanin pigments can be broadly divided into two types, dark-colored eumelanin and light-colored pheomelanin, both of which contribute to the protection of ultraviolet rays and that melanin synthesis is activated when irradiated with ultraviolet rays. It has been.
一方、シワはシミとともに皮膚老化の代表的な変化である。加齢に伴う皮膚の組織学的変化は日光暴露部と被覆部とでは大きく異なり、それぞれ、光老化及び生理的老化と区別されている。特に、顔面のシワが美容上問題となり、ここでは、生理的老化に加えて光老化の関与が大きい。この光老化には紫外線などにより生じる活性酸素などのフリーラジカルが主な原因と考えられており、紫外線による酸化障害として、脂質の過酸化、ＤＮＡ損傷、蛋白変性、代謝異常などが生じる。それらが、急性・慢性炎症、真皮細胞外マトリックスの変性を引き起こし、光老化につながると考えられている。 On the other hand, wrinkles are a typical change in skin aging along with stains. The histological changes of the skin with aging are greatly different between the sun-exposed part and the covering part, and are distinguished from photoaging and physiological aging, respectively. In particular, wrinkles on the face are a cosmetic problem, and here, photoaging is significant in addition to physiological aging. This photoaging is considered to be mainly caused by free radicals such as active oxygen generated by ultraviolet rays and the like, and as oxidation disorders by ultraviolet rays, lipid peroxidation, DNA damage, protein denaturation, metabolic abnormalities and the like occur. They are thought to cause acute and chronic inflammation and degeneration of the dermal extracellular matrix, leading to photoaging.
真皮細胞外マトリックスの変性は主に、活性酸素・フリーラジカルの繊維構造の分解・断片化作用によるものであり、また、活性酸素によりコラーゲン繊維の老化架橋が促進される。このようにして弾力繊維の変性が起こり、シワの原因になると考えられている。 Degeneration of the dermal extracellular matrix is mainly due to decomposition and fragmentation of the fiber structure of active oxygen and free radicals, and the aging cross-linking of collagen fibers is promoted by active oxygen. It is considered that the elastic fiber is denatured in this way and causes wrinkles.
従来より、このようなシミやシワの生成を防止することを目的として種々の方法が検討されてきた。 Conventionally, various methods have been studied for the purpose of preventing the generation of such spots and wrinkles.
その一つとしては、紫外線照射などにより生じたフリーラジカルを消去し、またメラニン色素産生に関与する酵素のチロシナーゼを阻害することでメラニン色素産生自体を抑制する方法が挙げられる。 One of them is a method of suppressing melanin pigment production itself by eliminating free radicals generated by ultraviolet irradiation and inhibiting tyrosinase, an enzyme involved in melanin pigment production.
上記作用を有する化合物としては、抗酸化作用のあるビタミンＣやビタミンＥが挙げられ、ビタミンＣが唯一の医薬品成分として古くから主に経口投与で用いられてきた。また、上記以外のビタミンと色素沈着に関連する事項としては以下の内容が知られている。 Examples of the compound having the above-mentioned action include vitamin C and vitamin E having an antioxidant action, and vitamin C has been used mainly for oral administration as the only pharmaceutical ingredient since ancient times. Moreover, the following contents are known as matters related to vitamins and pigmentation other than the above.
すなわち、リボフラビンはグルタチオン還元酵素の補酵素として重要であり、過酸化脂質の生成を抑制すること、またフリーラジカル捕捉剤として作用する可能性があること（例えば、非特許文献１参照。）、さらにリボフラビンを局所注射後に紫外線照射することが青色母斑の治療に有効であることが知られている（例えば、非特許文献２参照。）。 That is, riboflavin is important as a coenzyme for glutathione reductase, and may suppress the production of lipid peroxide and may act as a free radical scavenger (see, for example, Non-Patent Document 1). It is known that irradiation with ultraviolet rays after local injection of riboflavin is effective in treating blue nevus (see, for example, Non-Patent Document 2).
ニコチン酸アミドは、色素細胞から表皮細胞へのメラニンの転送を阻害することにより色素沈着を防止することが知られている（例えば、非特許文献３参照。）。 Nicotinamide is known to prevent pigmentation by inhibiting melanin transfer from pigment cells to epidermal cells (see, for example, Non-Patent Document 3).
パントテン酸カルシウムは、単独では紫外線照射後の色素沈着に対して効果がないが、ビタミンＣとの併用で色素沈着防止効果があることが知られている（例えば、非特許文献４参照。）。 Calcium pantothenate alone has no effect on pigmentation after ultraviolet irradiation, but is known to have a pigmentation-preventing effect when used in combination with vitamin C (see, for example, Non-Patent Document 4).
上記以外では外用の美白剤が主に用いられている。具体的には、メラニン色素産生自体を抑制するハイドロキノン誘導体（例えば、特許文献１参照。）、チロシナーゼ阻害による美白効果を期待したエラグ酸（例えば、非特許文献５参照。）、コウジ酸（例えば、特許文献２、３参照。）、アルブチン（例えば、特許文献４参照。）などが既に提案されているが、前述のとおり、メラニン色素は紫外線防御における重要な物質であり、これらの成分はメラニン色素産生自体を抑制するので必ずしも好ましいことではない。 Other than the above, external whitening agents are mainly used. Specifically, hydroquinone derivatives that suppress melanin pigment production itself (for example, see Patent Document 1), ellagic acid (for example, see Non-Patent Document 5) that is expected to have a whitening effect due to tyrosinase inhibition, kojic acid (for example, Patent Documents 2 and 3), arbutin (for example, refer to Patent Document 4) and the like have already been proposed. As described above, melanin pigments are important substances in UV protection, and these components are melanin pigments. Since production itself is suppressed, it is not always preferable.
しかしながら、上記公報及び文献のいずれにも、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上が効率的にメラノサイトの活性化を抑制し美白作用を有することについては何ら開示も示唆もされていない。また、それらからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物がより効果的に美白作用を有することも何ら開示も示唆もされていない。 However, in both of the above publications and literatures, it is said that at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate efficiently suppresses activation of melanocytes and has a whitening action. There is no disclosure or suggestion. Further, there is no disclosure or suggestion that a vitamin mixture composition containing three or more selected from the group consisting of these has a whitening action more effectively.
本発明の目的は、優れた美白作用を有する、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤及びそれらからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物を提供することにある。 An object of the present invention is a whitening agent having an excellent whitening action and having one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate as an active ingredient, and a group consisting of these 3 It is in providing the vitamin-mixing composition characterized by containing the seed | species or more.
本発明者らの研究によれば、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上が意外にも優れた美白作用を見出し、それらからなる群から選ばれる３種以上を組合せたビタミン混合組成物がさらに優れた美白作用を有することを見出し本発明を完成させた。 According to the study by the present inventors, one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate have surprisingly found an excellent whitening action and are selected from the group consisting of these 3 The present invention has been completed by finding that a vitamin mixture composition comprising a combination of more than one species has a further excellent whitening effect.
すなわち、本発明は、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤及びそれらからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物である。
好ましくは、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる２種以上を有効成分とする美白剤であり、さらに好ましくはリボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる３種以上を有効成分とする美白剤であり、最も好ましくはリボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムを有効成分とする美白剤である。
また、本発明は、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる３種以上を含有することを特徴とするビタミン混合組成物に関する。
That is, the present invention contains a whitening agent containing as an active ingredient at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate, and three or more selected from the group consisting thereof. It is a vitamin mixture composition characterized.
Preferably, it is a whitening agent containing two or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate, more preferably riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate. A whitening agent containing three or more selected from the group consisting of active ingredients, and most preferably a whitening agent containing riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate as active ingredients.
The present invention also relates to a vitamin mixture composition comprising three or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate.
本発明のリボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤は、優れた美白作用を示し、それらからなる群から選ばれる３種以上を組合せたビタミン混合組成物がさらに優れた美白作用を示し、色素沈着が悪化するストレス環境下においても優れた美白効果を示した。従って、本発明の美白剤及びビタミン混合組成物が色素沈着を予防し、シミやソバカスの紫外線による悪化を抑制することが示唆され、美白剤として有用である。 The whitening agent comprising one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate of the present invention as an active ingredient exhibits an excellent whitening action, and three or more selected from the group consisting of these The vitamin mixture composition combined with the above showed an excellent whitening effect, and also showed an excellent whitening effect even in a stress environment where pigmentation worsens. Therefore, it is suggested that the whitening agent and vitamin mixture composition of the present invention prevents pigmentation and suppresses deterioration of stains and buckwheat by ultraviolet rays, and is useful as a whitening agent.
以下、本発明について詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明に用いられるリボフラビンは、第十四改正日本薬局方、（株式会社じほう発行、２００１年、以下局方と略記する）、７４９−７５０頁に記載のものが挙げられる。 Examples of the riboflavin used in the present invention include those described in the 14th revised Japanese Pharmacopoeia (issued by Jiho Co., Ltd., 2001, hereinafter abbreviated as “Pharmacopeia”), pages 749-750.
本発明に用いられる塩酸ピリドキシンは、局方、３６１頁に記載のものが挙げられる。 Examples of the pyridoxine hydrochloride used in the present invention include those described in Pharmacopeia, page 361.
本発明に用いられるニコチン酸アミドは、局方、５８８頁に記載のものが挙げられる。 Examples of nicotinamide used in the present invention include those described in the Japanese Pharmacopoeia, page 588.
本発明に用いられるパントテン酸カルシウムは、局方、６１５−６１６頁に記載のものが挙げられる。 Examples of the calcium pantothenate used in the present invention include those described in the Japanese Pharmacopoeia, pages 615-616.
本発明の美白剤及びビタミン混合組成物としては、固形剤、半固形剤、液剤等特に制限されるものではなく、具体的には錠剤、細粒剤、顆粒剤、散剤、カプセル剤、チュアブル剤、発泡剤、ドライシロップ剤、ゼリー剤、ゼリードロップ剤、液剤等の形態をした食品及び医薬品などが挙げられる。 The whitening agent and vitamin mixture composition of the present invention is not particularly limited to solid agents, semi-solid agents, liquid agents, etc., and specifically, tablets, fine granules, granules, powders, capsules, chewable agents , Foods and pharmaceuticals in the form of foaming agents, dry syrups, jelly agents, jelly drop agents, liquid agents and the like.
本発明の美白剤及びビタミン混合組成物は、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を混合したものをそのままの形で使用することもできるが、その他の成分として、通常の食品及び医薬品に用いられるものを使用することができる。例えば結晶セルロース、ショ糖脂肪酸エステル、白糖等の賦形剤を加え、例えば乾式顆粒打錠法あるいは湿式顆粒打錠法により造粒して製造することができる。 The whitening agent and vitamin mixture composition of the present invention can be used as it is by mixing one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate. As the components, those used in ordinary foods and pharmaceuticals can be used. For example, it can be produced by adding an excipient such as crystalline cellulose, sucrose fatty acid ester, sucrose and the like, and granulating it by, for example, dry granulation tableting method or wet granulation tableting method.
また、通常、液状の食品及び医薬品に使用される浸潤剤、乳化剤、分散助剤、界面活性剤、甘味料、酸味料、糖アルコール、フレーバー、芳香物質等賦形剤を加えて溶解し、液体の状態として製造することもできる。 Ordinarily, wetting agents, emulsifiers, dispersion aids, surfactants, sweeteners, acidulants, sugar alcohols, flavors, fragrances, and other excipients used in liquid foods and pharmaceuticals are added to dissolve and liquid It can also be manufactured as a state.
本発明のリボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上を有効成分とする美白剤及びそれらからなる群から選ばれる３種以上を含有することを特徴ビタミン混合組成物における、各有効成分の配合割合は用いられる種類によっても若干異なるが、全組成物１０００重量部当たり、リボフラビンは０．４〜３０重量部、好ましくは２〜３０重量部、塩酸ピリドキシンは０．５〜１００重量部、好ましくは５〜１００重量部、ニコチン酸アミドは２〜６０重量部、好ましくは１２〜６０重量部及びパントテン酸カルシウムは５〜３０重量部、好ましくは５〜１５重量部である。当該範囲内の使用であれば、優れた美白効果を示し、コスト的にも有効である。 A whitening agent containing at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate according to the present invention, and 3 or more selected from the group consisting of these. The proportion of each active ingredient in the composition varies slightly depending on the type used, but riboflavin is 0.4 to 30 parts by weight, preferably 2 to 30 parts by weight, and pyridoxine hydrochloride is 0 per 1000 parts by weight of the total composition. 0.5-100 parts by weight, preferably 5-100 parts by weight, nicotinamide 2-60 parts by weight, preferably 12-60 parts by weight and calcium pantothenate 5-30 parts by weight, preferably 5-15 parts by weight It is. If it is used within this range, it exhibits an excellent whitening effect and is also effective in terms of cost.
さらに具体的には、一日の投与量が、リボフラビン０．４〜３０ｍｇ、塩酸ピリドキシン０．５〜１００ｍｇ、ニコチン酸アミド２〜６０ｍｇ及びパントテン酸カルシウム５〜３０ｍｇとなるよう適宜混合する。 More specifically, the daily dose is appropriately mixed so as to be 0.4 to 30 mg of riboflavin, 0.5 to 100 mg of pyridoxine hydrochloride, 2 to 60 mg of nicotinamide, and 5 to 30 mg of calcium pantothenate.
本発明の美白剤及びビタミン混合組成物は、必須成分である上記化合物の他に通常の医薬品及び飲食品において使用されるアスコルビン酸、コウジ酸、アルブチン、胎盤抽出物、ビタミンＥ、システイン、グルタチオン等の公知の美白剤、ビタミンＢ１、ビタミンＤ、アミノ酸、ペプチド、蛋白質等を配合することができる。 The whitening agent and vitamin-mixed composition of the present invention include ascorbic acid, kojic acid, arbutin, placental extract, vitamin E, cysteine, glutathione and the like used in ordinary pharmaceuticals and foods and drinks in addition to the above-mentioned compounds that are essential components Known whitening agents, vitamin B 1 , vitamin D, amino acids, peptides, proteins and the like can be blended.
本発明の美白剤及びビタミン混合組成物は、美白剤として、通常成人１日当たり１〜３回に分けて経口投与する。 The whitening agent and vitamin mixture composition of the present invention is orally administered as a whitening agent, usually divided into 1 to 3 times per day for an adult.
以下に試験例を挙げて本発明を詳細に説明する。リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムは市販のものを用いた。 Hereinafter, the present invention will be described in detail with reference to test examples. Commercially available riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate were used.
[試験例]
試験例１（紫外線照射後のメラノサイト増殖活性化抑制試験）
（１）試験方法
ＤＢＡ／２ＮＣｒｊマウス（雄性、６週齢）６匹を１群として用いた。体重を測定し、
表１に示す被験物質を１％レシチンに溶解させて用いた。５群のＤＢＡ／２ＮＣｒｊマウスにそれぞれ試験試料１ａ〜１ｄ、対照試料１をゾンデで直接胃の中に投与した。その後、投与１時間後に医療用紫外線照射装置デルマレー（クリニカル・サプライ社製）を用いて、中波長紫外線を５分間０．０９Ｊ／ｃｍ２照射した。被験試料投与と照射を１日１回、９日間行った。次ぎに１０日目にＤＢＡ／２ＮＣｒｊマウスの両耳を採取し、外側の皮膚が上になるように置き、左右の耳から１箇所ずつ６ｍｍのトレパンで皮膚を採取した。その後、外側の皮膚を採取し、定法に従ってメラニン色素を産生しているメラノサイトの指標であるド−パ陽性メラノサイトの染色を行い、顕微鏡下でメラノサイト数を数え、１ｍｍ２当たりのメラノサイト数を計測した。なお、１群のＤＢＡ／２ＮＣｒｊマウスは中波長紫外線を照射せず、同様に実験を行った（非照射投与群という）。
[Test example]
Test Example 1 (Inhibition test of melanocyte proliferation activation after UV irradiation)
(1) Test method Six DBA / 2NCrj mice (male, 6 weeks old) were used as one group. Measure your weight
The test substances shown in Table 1 were dissolved in 1% lecithin and used. Five groups of DBA / 2NCrj mice were administered test samples 1a-1d and control sample 1 respectively directly into the stomach with a sonde. Thereafter, 1 hour after administration, medium wavelength ultraviolet rays were irradiated for 5 minutes at 0.09 J / cm 2 using a medical ultraviolet irradiation device Dermaray (manufactured by Clinical Supply). Test sample administration and irradiation were performed once a day for 9 days. Next, on the 10th day, both ears of DBA / 2NCrj mice were collected, placed so that the outer skin was on top, and the skin was collected with a 6 mm trepan from each of the left and right ears. Thereafter, the outer skin was collected, and dopa-positive melanocytes, which are indicators of melanocytes producing melanin pigments, were stained according to a standard method. The number of melanocytes was counted under a microscope, and the number of melanocytes per mm 2 was measured. . Note that one group of DBA / 2NCrj mice was not irradiated with medium wavelength ultraviolet light, and was similarly tested (referred to as non-irradiated administration group).
（２）検定方法
結果の判定は、対照試料投与群１と本発明の試験試料投与群１ａ〜１ｄのそれぞれのドーパ陽性メラノサイト数を比較して行った。また、有意差検定はダネット（ｄｕｎｎｅｔｔ）検定を用いた。
（３）試験結果
結果を表２に示す。表２から明らかなようにリボフラビン、塩酸ピリドキシン、パントテン酸カルシウム及びニコチン酸アミドは有意に紫外線照射によるド−パ陽性メラノサイト数の増加を抑制し、本発明の美白剤が色素沈着防止に有効であることが示された。
(2) Assay method The results were determined by comparing the number of dopa-positive melanocytes in the control sample administration group 1 and the test sample administration groups 1a to 1d of the present invention. In addition, Dunnett's test was used for the significant difference test.
(3) Test results The results are shown in Table 2. As is apparent from Table 2, riboflavin, pyridoxine hydrochloride, calcium pantothenate and nicotinamide significantly suppress the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation, and the whitening agent of the present invention is effective in preventing pigmentation. It was shown that.
試験例２（紫外線照射後のメラノサイト増殖活性化抑制試験）
（１）試験方法
表３に示す被験物質を用いる以外は試験例１と同様に試験を行った。
Test Example 2 (Test for inhibiting melanocyte proliferation activation after UV irradiation)
(1) Test method Tests were conducted in the same manner as in Test Example 1 except that the test substances shown in Table 3 were used.
（２）検定方法
試験例１と同様の方法を用いた。
(2) Test method The same method as in Test Example 1 was used.
（３）試験結果
結果を表４に示す。表４から明らかなように本発明のビタミン混合組成物は有意に紫外線照射によるド−パ陽性メラノサイト数の増加を抑制した。また、参考試料２ａ〜２ｃのビタミンＣ、ビタミンＥに比べて本発明のビタミン混合組成物は有意に紫外線照射によるド−パ陽性メラノサイト数の増加を抑制した。
(3) Test results Table 4 shows the results. As is apparent from Table 4, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation. Moreover, compared with vitamin C and vitamin E of reference samples 2a to 2c, the vitamin mixed composition of the present invention significantly suppressed an increase in the number of dopa-positive melanocytes due to ultraviolet irradiation.
試験例３（紫外線照射後のメラノサイト増殖活性化抑制試験）
（１）試験方法
表５に示す被験物質を用いる以外は試験例１と同様に試験を行った
Test Example 3 (Test for inhibiting melanocyte proliferation activation after UV irradiation)
(1) Test method The test was performed in the same manner as in Test Example 1 except that the test substances shown in Table 5 were used.
（２）検定方法
試験例１と同様の方法を用いた。
（３）試験結果
結果を表６に示す。表６から明らかなように本発明のビタミン混合組成物は有意に紫外線照射によるド−パ陽性メラノサイト数の増加を抑制した。
(2) Test method The same method as in Test Example 1 was used.
(3) Test results Table 6 shows the results. As is apparent from Table 6, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation.
尚、抑制率は下記式より求めた。
抑制率（％）＝｛（対照群−ストレス群）−（各試料群−ストレス群）｝／（対照群−ストレス群）×１００
In addition, the suppression rate was calculated | required from the following formula.
Inhibition rate (%) = {(control group−stress group) − (each sample group−stress group)} / (control group−stress group) × 100
試験例３（ストレス環境飼育下での紫外線照射後のメラノサイト増殖活性化抑制試験）
（１）試験方法
ＤＢＡ／２ＮＣｒｊマウス（雄性、６週齢）６匹を１群として用い、通常環境下と過密ストレス環境下で飼育を行った。すなわち、非照射投与群（紫外線非照射）と紫外線照射群（紫外線照射のみ）は、飼育を通常ケージ（３０×２０×１２ｃｍ）で行い、ストレス群（過密ストレス環境飼育のみ）とストレス下紫外線照射群（対象群；過密ストレス環境飼育で紫外線照射）及び試験試料投与群は、飼育を過密ストレスケージ（１４×７×８ｃｍ）で行った。試験には、表７に示す被験物質を０．５％カルメロースナトリウムに溶解させて用いた。８群のＤＢＡ／２ＮＣｒｊマウスにそれぞれ試験試料４ａと４ｂ、参考試料４及び対照試料４をゾンデで直接胃の中に投与した。その後、投与１時間後に医療用紫外線照射装置デルマレー（クリニカル・サプライ社製）を用いて、中波長紫外線を５分間０．０４５Ｊ／ｃｍ２照射した。過密ストレス環境飼育したＤＢＡ／２ＮＣｒｊマウスは紫外線照射の際には通常ケージを用いて行った。被験試料投与と照射を１日１回、９日間行った。９日目の照射５〜３０分の間にＤＢＡ／２ＮＣｒｊマウスをジエチルエーテル麻酔をし採血後、両耳を採取し、外側の皮膚が上になるように置き、左右の耳から１箇所ずつ６ｍｍのトレパンで皮膚を採取した。その後、外側の皮膚を採取し、定法に従ってメラニン色素を産生しているメラノサイトの指標であるド−パ陽性メラノサイトの染色を行い、顕微鏡下でメラノサイト数を数え、１ｍｍ２当たりのメラノサイト数を計測した。なお、１群のＤＢＡ／２ＮＣｒｊマウスは中波長紫外線を照射せず、同様に実験を行った。また、採血した血清については、血清中のＡＣＴＨ濃度を、ＭＤ Ｂｉｏｓｃｉｅｎｃｅ社キットのＥＬＩＳＡ法により測定した。
Test Example 3 (Inhibition test for activation of melanocyte proliferation after irradiation with ultraviolet light in a stress environment)
(1) Test method Six DBA / 2NCrj mice (male, 6 weeks old) were used as a group and reared in a normal environment and in an overstressed stress environment. That is, the non-irradiated administration group (non-ultraviolet irradiation) and the ultraviolet irradiation group (only ultraviolet irradiation) are reared in a normal cage (30 × 20 × 12 cm), and the stress group (overcrowded stress environment only) and ultraviolet irradiation under stress. The group (subject group; ultraviolet irradiation in an overcrowded stress environment rearing) and the test sample administration group were reared in an overstressed stress cage (14 × 7 × 8 cm). In the test, the test substances shown in Table 7 were dissolved in 0.5% carmellose sodium and used. Eight groups of DBA / 2NCrj mice were administered test samples 4a and 4b, reference sample 4 and control sample 4 respectively directly into the stomach with a sonde. Thereafter, 1 hour after administration, medium wavelength ultraviolet rays were irradiated for 5 minutes at 0.045 J / cm 2 using a medical ultraviolet irradiation device Dermaray (manufactured by Clinical Supply). DBA / 2NCrj mice bred in an overstressed environment were usually caged during UV irradiation. Test sample administration and irradiation were performed once a day for 9 days. DBA / 2NCrj mice were anesthetized with diethyl ether for 5 to 30 minutes after irradiation on the 9th day, and after collecting blood, both ears were collected and placed with the outer skin on top, 6 mm each from the left and right ears. The skin was collected with a trepan. Thereafter, the outer skin was collected, and dopa-positive melanocytes, which are indicators of melanocytes producing melanin pigments, were stained according to a standard method. The number of melanocytes was counted under a microscope, and the number of melanocytes per mm 2 was measured. . In addition, a group of DBA / 2NCrj mice were not irradiated with medium wavelength ultraviolet rays, and the same experiment was conducted. For the collected blood serum, the ACTH concentration in the serum was measured by the ELISA method of MD Bioscience kit.
（２）検定方法
結果の判定は、対照群と本発明の試験試料４ａ、４ｂ投与群及び参考試料４投与群のそれぞれのドーパ陽性メラノサイト数を比較して行った。また、有意差検定はダネット（ｄｕｎｎｅｔｔ）検定を用いた。
(2) Assay method The results were determined by comparing the number of dopa-positive melanocytes in the control group, the test sample 4a and 4b administration group of the present invention, and the reference sample 4 administration group. In addition, Dunnett's test was used for the significant difference test.
（３）試験結果
ドーパ陽性メラノサイト数の結果を表８に、ＡＣＴＨ濃度を表９に示す。表８から明らかなように本発明のビタミン混合組成物はストレス環境下の紫外線照射によるド−パ陽性メラノサイト数の増加を有意に抑制した。また、参考試料のビタミンＣに比べて本発明の組成物は低用量で有効で、紫外線照射によるド−パ陽性メラノサイト数の増加を有意に抑制した。また、表９から明らかなように、ストレス環境下の紫外線照射により顕著に増加するＡＣＴＨに対して、本発明の組成物は有意に抑制することが明らかになり、本発明の組成物が色素沈着を予防し、シミやソバカスの紫外線による悪化を抑制する可能性があることが示唆された。
(3) Test results The results of the number of dopa-positive melanocytes are shown in Table 8, and the ACTH concentration is shown in Table 9. As is apparent from Table 8, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes by ultraviolet irradiation under a stress environment. In addition, the composition of the present invention was effective at a low dose as compared with vitamin C as a reference sample, and significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation. Further, as is apparent from Table 9, it was revealed that the composition of the present invention significantly suppresses ACTH that is significantly increased by ultraviolet irradiation under a stress environment, and the composition of the present invention is pigmented. It was suggested that there is a possibility of preventing the deterioration of spots and buckwheat caused by ultraviolet rays.
以下に、実施例を挙げて本発明をさらに具体的に説明する。 Hereinafter, the present invention will be described more specifically with reference to examples.
実施例１（錠剤）
（処方）
リボフラビン ０．８ｇ
塩酸ピリドキシン １．０ｇ
ニコチン酸アミド ２．０ｇ
結晶セルロース ８０．０ｇ
二酸化ケイ素 ６．０ｇ
ソルビトール １９８．２ｇ
ショ糖脂肪酸エステル １２．０ｇ
――――――――――――――――――――――――――――――
合計 ３００．０ｇ
Example 1 (tablets)
(Prescription)
Riboflavin 0.8g
1.0 g of pyridoxine hydrochloride
Nicotinamide 2.0g
Crystalline cellulose 80.0g
6.0g silicon dioxide
Sorbitol 198.2g
Sucrose fatty acid ester 12.0 g
――――――――――――――――――――――――――――――
Total 300.0g
（製造方法）
上記の各成分を混合し、その混合物を打錠機で１錠３００ｍｇに打錠して１錠中にリボフラビン０．８ｍｇ、塩酸ピリドキシン１．０ｍｇ、ニコチン酸アミド２．０ｍｇ含む実施例１の錠剤を得る。
(Production method)
The above ingredients were mixed, and the mixture was tableted into 300 mg tablets with a tableting machine, and each tablet contained 0.8 mg riboflavin, 1.0 mg pyridoxine hydrochloride, and 2.0 mg nicotinamide amide. Get.
実施例２（錠剤）
リボフラビン０．８ｇ及びソルビトール１９８．２ｇをパントテン酸カルシウム３．２ｇ及びソルビトール１９５．８ｇに代えた以外は実施例１と同様にして調製し、実施例２の錠剤を得る。
Example 2 (tablets)
A tablet of Example 2 is obtained in the same manner as in Example 1 except that 0.8 g of riboflavin and 198.2 g of sorbitol are replaced with 3.2 g of calcium pantothenate and 195.8 g of sorbitol.
実施例３（錠剤）
塩酸ピリドキシン１．０ｇ及びソルビトール１９８．２ｇをパントテン酸カルシウム３．２ｇ及びソルビトール１９６．０ｇに代えた以外は実施例１と同様にして調製し、実施例３の錠剤を得る。
Example 3 (tablets)
A tablet of Example 3 is obtained in the same manner as in Example 1 except that 1.0 g of pyridoxine hydrochloride and 198.2 g of sorbitol are replaced with 3.2 g of calcium pantothenate and 196.0 g of sorbitol.
実施例４（錠剤）
ニコチン酸アミド２．０ｇ及びソルビトール１９８．２ｇをパントテン酸カルシウム３．２ｇ及びソルビトール１９７．０ｇに代えた以外は実施例１と同様にして調製し、実施例４の錠剤を得る。
Example 4 (tablets)
The tablets of Example 4 are obtained in the same manner as in Example 1 except that 2.0 g of nicotinamide and 198.2 g of sorbitol are replaced with 3.2 g of calcium pantothenate and 197.0 g of sorbitol.
実施例５（錠剤）
ソルビトール１９８．２ｇをパントテン酸カルシウム３．２ｇ及びソルビトール１９５．０ｇに代えた以外は実施例１と同様にして調製し、実施例５の錠剤を得る。
Example 5 (tablets)
A tablet of Example 5 is obtained in the same manner as in Example 1 except that 198.2 g of sorbitol is replaced with 3.2 g of calcium pantothenate and 195.0 g of sorbitol.
実施例６（液剤）
（処方）
リボフラビン １ｇ
塩酸ピリドキシン ５ｇ
ニコチン酸アミド ５ｇ
クエン酸 ２８ｇ
リンゴ酸 ２０ｇ
スクラロース ５ｇ
香料 １０ｇ
精製水 適 量
――――――――――――――――――――――――――――――
全量 １５ｋｇ
Example 6 (Liquid)
(Prescription)
Riboflavin 1g
5g pyridoxine hydrochloride
Nicotinamide 5g
Citric acid 28g
Malic acid 20g
5g sucralose
Fragrance 10g
Purified water appropriate amount ――――――――――――――――――――――――――――――
Total amount 15kg
（製造方法）
上記のリボフラビンからスクラロースまでの各成分を加えて加熱溶解し、冷後、香料及び精製水を加えて全量１５ｋｇとする。この液を１００ｍＬずつ容器に分注し、実施例６の液剤を得る。
(Production method)
Add each of the above components from riboflavin to sucralose and dissolve with heating. After cooling, add fragrance and purified water to a total volume of 15 kg. 100 mL of this solution is dispensed into a container, and the liquid agent of Example 6 is obtained.
実施例７（液剤）
リボフラビン１ｇをパントテン酸カルシウム５ｇに代えた以外は実施例６と同様にして調製し、実施例７の液剤を得る。
Example 7 (Liquid)
A liquid preparation of Example 7 is obtained in the same manner as in Example 6 except that 1 g of riboflavin is replaced with 5 g of calcium pantothenate.
実施例８（液剤）
塩酸ピリドキシン５ｇをパントテン酸カルシウム５ｇに代えた以外は実施例６と同様にして調製し、実施例８の液剤を得る。
Example 8 (Liquid)
A solution of Example 8 is obtained in the same manner as in Example 6 except that 5 g of pyridoxine hydrochloride is replaced with 5 g of calcium pantothenate.
実施例９（液剤）
ニコチン酸アミド５ｇをパントテン酸カルシウム５ｇに代えた以外は実施例６と同様にして調製し、実施例９の液剤を得る。
Example 9 (Liquid)
A liquid preparation of Example 9 is obtained in the same manner as in Example 6 except that 5 g of nicotinic acid amide is replaced with 5 g of calcium pantothenate.
実施例１０（液剤）
パントテン酸カルシウム５ｇを加える以外は実施例６と同様にして調製し、実施例１０の液剤を得る。
Example 10 (Liquid)
A liquid preparation of Example 10 is obtained in the same manner as in Example 6 except that 5 g of calcium pantothenate is added.
実施例１１（錠剤）
ソルビトール１９８．２ｇをバラの花びらエキス１０．０ｇ及びソルビトール１８８．２ｇに代えた以外は実施例１と同様にして調製し、実施例１１の錠剤を得る。
Example 11 (tablets)
A tablet of Example 11 is obtained in the same manner as in Example 1 except that 198.2 g of sorbitol is replaced with 10.0 g of rose petal extract and 188.2 g of sorbitol.
実施例１２（液剤）
バラの花びらエキス５ｇを追加した以外は実施例６と同様にして調製し、実施例１２の液剤を得る。
Example 12 (Liquid)
A liquid preparation of Example 12 is obtained in the same manner as in Example 6 except that 5 g of rose petal extract is added.
本発明に係る、リボフラビン、塩酸ピリドキシン、ニコチン酸アミド及びパントテン酸カルシウムからなる群から選ばれる１種以上からなる美白剤は、優れた美白作用を示す。それらからなる群より選ばれる３種以上からなることを特徴とするビタミン混合組成物は
、さらに優れた美白作用を示す。さらに本発明のビタミン混合組成物は、ストレスで増加するＡＣＴＨの分泌を抑える作用が明らかであり、日常生活で受ける様々なストレスで悪化する色素沈着に対しても優れた効果を発揮することで、頑固なシミ・ソバカスなどの治療効果も期待できる。
The whitening agent comprising at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate according to the present invention exhibits an excellent whitening action. A vitamin mixed composition characterized by comprising three or more selected from the group consisting of them exhibits a further excellent whitening effect. Furthermore, the vitamin mixture composition of the present invention clearly has an action of suppressing the secretion of ACTH that increases due to stress, and exhibits an excellent effect on pigmentation that deteriorates due to various stresses received in daily life. It can also be expected to have stubborn stains and freckles.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003420438A JP4712300B2 (en) | 2002-12-26 | 2003-12-18 | Whitening agent and vitamin mixture composition |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002376392 | 2002-12-26 | ||
| JP2002376392 | 2002-12-26 | ||
| JP2003420438A JP4712300B2 (en) | 2002-12-26 | 2003-12-18 | Whitening agent and vitamin mixture composition |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010117409A Division JP2010174049A (en) | 2002-12-26 | 2010-05-21 | Skin whitening agent and vitamin mixed composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004217629A JP2004217629A (en) | 2004-08-05 |
| JP4712300B2 true JP4712300B2 (en) | 2011-06-29 |
Family
ID=32911120
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003420438A Expired - Lifetime JP4712300B2 (en) | 2002-12-26 | 2003-12-18 | Whitening agent and vitamin mixture composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4712300B2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009256326A (en) * | 2008-03-21 | 2009-11-05 | Kose Corp | Skin whitening preparation, and skincare preparation |
| JP2010159252A (en) * | 2008-12-12 | 2010-07-22 | Daiichi Sankyo Healthcare Co Ltd | Melanosome traffick inhibitor, and method for the same |
| JP6823428B2 (en) * | 2016-11-16 | 2021-02-03 | 株式会社ファンケル | IL-1 receptor antagonist (IL-1RA) production promoting composition |
| EP3581187A4 (en) * | 2017-02-08 | 2020-11-04 | Oriental Yeast Co., Ltd. | Skin pigmentation inhibitor |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05186324A (en) * | 1991-12-29 | 1993-07-27 | Sunstar Inc | Beautifying cosmetic |
| JPH05505935A (en) * | 1990-02-05 | 1993-09-02 | ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | Extended release formulation of vitamins, minerals and other beneficial supplements |
| JPH0680564A (en) * | 1992-09-03 | 1994-03-22 | Meiji Seika Kaisha Ltd | Anti-pigmentation agent |
| JPH09291021A (en) * | 1996-04-25 | 1997-11-11 | Sunstar Inc | Beautifying and whitening cosmetic |
| JPH10158148A (en) * | 1996-12-02 | 1998-06-16 | Kanebo Ltd | Skin-whitening cosmetic |
| JPH1156299A (en) * | 1997-08-19 | 1999-03-02 | Morikawa Kenkoudou Kk | Processed food containing vitamins |
| JP2000297011A (en) * | 1999-04-12 | 2000-10-24 | Kanebo Ltd | Bleaching cosmetic |
| KR20000066978A (en) * | 1999-04-22 | 2000-11-15 | 성재갑 | Composition of cosmetics comprising effect of improving subdued skin color |
-
2003
- 2003-12-18 JP JP2003420438A patent/JP4712300B2/en not_active Expired - Lifetime
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05505935A (en) * | 1990-02-05 | 1993-09-02 | ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | Extended release formulation of vitamins, minerals and other beneficial supplements |
| JPH05186324A (en) * | 1991-12-29 | 1993-07-27 | Sunstar Inc | Beautifying cosmetic |
| JPH0680564A (en) * | 1992-09-03 | 1994-03-22 | Meiji Seika Kaisha Ltd | Anti-pigmentation agent |
| JPH09291021A (en) * | 1996-04-25 | 1997-11-11 | Sunstar Inc | Beautifying and whitening cosmetic |
| JPH10158148A (en) * | 1996-12-02 | 1998-06-16 | Kanebo Ltd | Skin-whitening cosmetic |
| JPH1156299A (en) * | 1997-08-19 | 1999-03-02 | Morikawa Kenkoudou Kk | Processed food containing vitamins |
| JP2000297011A (en) * | 1999-04-12 | 2000-10-24 | Kanebo Ltd | Bleaching cosmetic |
| KR20000066978A (en) * | 1999-04-22 | 2000-11-15 | 성재갑 | Composition of cosmetics comprising effect of improving subdued skin color |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004217629A (en) | 2004-08-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101102746B (en) | Skin-condition improving composition comprising vaccinium uliginosum extract and method for preparation thereof | |
| WO2008045272A2 (en) | Compositions and methods for skin lightening | |
| JP2002193738A (en) | Use of at least one extract from at least one azalea plant in composition for treating symptom of skin aging | |
| JP2009508895A (en) | Use of opioid receptor antagonists | |
| ES2937058T3 (en) | Peptide having skin whitening activity and use thereof | |
| KR20210097729A (en) | Polypeptides and methods for improving skin conditions | |
| KR20040068986A (en) | Drugs for ameliorating itch, rough skin or hypersensitive skin or for whitening via inhibition of the production and release of stem cell factor | |
| KR20090054723A (en) | Oral composition for beauty culture of skin with moisturizing effect | |
| WO2004021967A2 (en) | Depigmenting composition for the skin comprising adapalene and at least one depigmenting agent | |
| JP2010174049A (en) | Skin whitening agent and vitamin mixed composition | |
| JP2013533308A (en) | Pharmaceutical or cosmetic composition comprising nicotinic acid adenine dinucleotide phosphate or a derivative thereof | |
| JP4712300B2 (en) | Whitening agent and vitamin mixture composition | |
| CN112043640B (en) | Composition and application thereof in preparation of anti-glycosylation cosmetics | |
| JP2001019607A (en) | Skin cosmetic | |
| KR101863297B1 (en) | Composition for preventing or improving skin wrinkle comprising chlorogenic acid and rutin compound as active ingredient | |
| JP2004203812A (en) | Oral composition and bleaching agent containing the same as essential component | |
| JP2009235044A (en) | ENDOTHELIN-1 mRNA EXPRESSION INHIBITOR, MATRIX METALLOPROTEASE-9 mRNA EXPRESSION INHIBITOR, COLLAGEN PRODUCTION PROMOTER, PROFILAGGRIN PRODUCTION PROMOTER, FILAGGRIN PRODUCTION PROMOTER AND AQUAPORIN 3 mRNA EXPRESSION PROMOTER | |
| JP2006056831A (en) | Protein oxidation inhibitor | |
| JP2011513192A (en) | Topical composition comprising fluocinolone acetonide for use in skin decolorization | |
| JP2009007336A (en) | Alpha-glycosylhesperidin-containing melanin reducing agent, skin brightness reduction inhibitor, skin viscoelasticity reduction inhibitor, sebum reduction inhibitor, scf production inhibitor and itch inhibitor for oral administration/ingestion | |
| ES2939257T3 (en) | Peptide with skin whitening activity and use thereof | |
| JP2014520166A (en) | Skin whitening composition containing Madecasoside | |
| CN112353807A (en) | Application of sialic acid in preparation of melanin pigmentation inhibitor | |
| KR100574850B1 (en) | Skin care composition containing synthetic palmitoyl pentapeptide | |
| JP2684561B2 (en) | Pigmentation inhibitor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050707 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20060710 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20060712 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090310 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090423 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100330 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100521 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100622 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100908 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20101007 |
|
| 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: 20110322 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110323 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4712300 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140401 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140401 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20210401 Year of fee payment: 10 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term | ||
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
| R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |