CN104105473A - 皮肤美白组合物 - Google Patents
皮肤美白组合物 Download PDFInfo
- Publication number
- CN104105473A CN104105473A CN201380009238.4A CN201380009238A CN104105473A CN 104105473 A CN104105473 A CN 104105473A CN 201380009238 A CN201380009238 A CN 201380009238A CN 104105473 A CN104105473 A CN 104105473A
- Authority
- CN
- China
- Prior art keywords
- oligonucleotide
- skin
- nucleotide
- compositions
- sirna
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 62
- 206010040829 Skin discolouration Diseases 0.000 title claims abstract description 19
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 49
- 108020004459 Small interfering RNA Proteins 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000002773 nucleotide Substances 0.000 claims description 37
- 125000003729 nucleotide group Chemical group 0.000 claims description 37
- 239000002537 cosmetic Substances 0.000 claims description 17
- 239000007788 liquid Substances 0.000 claims description 12
- -1 frost Substances 0.000 claims description 10
- 239000000344 soap Substances 0.000 claims description 10
- 239000000499 gel Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 229920000742 Cotton Polymers 0.000 claims description 5
- 230000001815 facial effect Effects 0.000 claims description 5
- 239000006260 foam Substances 0.000 claims description 5
- 239000000839 emulsion Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 abstract description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 1
- 210000003491 skin Anatomy 0.000 description 24
- 230000000475 sunscreen effect Effects 0.000 description 12
- 239000000516 sunscreening agent Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 239000000194 fatty acid Substances 0.000 description 11
- 235000014113 dietary fatty acids Nutrition 0.000 description 9
- 229930195729 fatty acid Natural products 0.000 description 9
- 150000004665 fatty acids Chemical class 0.000 description 9
- 230000036564 melanin content Effects 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 239000006071 cream Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 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
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 230000033228 biological regulation Effects 0.000 description 6
- 239000007854 depigmenting agent Substances 0.000 description 6
- 210000002510 keratinocyte Anatomy 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 5
- 210000002752 melanocyte Anatomy 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 4
- 229960004705 kojic acid Drugs 0.000 description 4
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 4
- 229960003512 nicotinic acid Drugs 0.000 description 4
- 235000001968 nicotinic acid Nutrition 0.000 description 4
- 239000011664 nicotinic acid Substances 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000012641 Pigmentation disease Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- NZZIMKJIVMHWJC-UHFFFAOYSA-N dibenzoylmethane Chemical compound C=1C=CC=CC=1C(=O)CC(=O)C1=CC=CC=C1 NZZIMKJIVMHWJC-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108050009340 Endothelin Proteins 0.000 description 2
- 102000002045 Endothelin Human genes 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000008099 melanin synthesis Effects 0.000 description 2
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-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
- 238000005457 optimization Methods 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 239000000080 wetting agent Substances 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
- OIQXFRANQVWXJF-QBFSEMIESA-N (2z)-2-benzylidene-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one Chemical compound CC1(C)C2CCC1(C)C(=O)\C2=C/C1=CC=CC=C1 OIQXFRANQVWXJF-QBFSEMIESA-N 0.000 description 1
- 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 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- 150000005207 1,3-dihydroxybenzenes Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- RMTZJDQQUXFDOJ-UHFFFAOYSA-N 2-hydroxy-3,4-diphenylbenzoic acid Chemical compound C=1C=CC=CC=1C1=C(O)C(C(=O)O)=CC=C1C1=CC=CC=C1 RMTZJDQQUXFDOJ-UHFFFAOYSA-N 0.000 description 1
- WSSJONWNBBTCMG-UHFFFAOYSA-N 2-hydroxybenzoic acid (3,3,5-trimethylcyclohexyl) ester Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C1=CC=CC=C1O WSSJONWNBBTCMG-UHFFFAOYSA-N 0.000 description 1
- KVYRCBOUKXJXDK-UHFFFAOYSA-N 3,4-dimethylphenazine-1,2-diamine hydrochloride Chemical compound Cl.C1=CC=CC2=NC3=C(C)C(C)=C(N)C(N)=C3N=C21 KVYRCBOUKXJXDK-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 240000004307 Citrus medica Species 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 102000017914 EDNRA Human genes 0.000 description 1
- 102000017930 EDNRB Human genes 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
- 102000030168 Endothelin A Receptor Human genes 0.000 description 1
- 108010090549 Endothelin A Receptor Proteins 0.000 description 1
- 102000013128 Endothelin B Receptor Human genes 0.000 description 1
- 108010090557 Endothelin B Receptor Proteins 0.000 description 1
- FMRHJJZUHUTGKE-UHFFFAOYSA-N Ethylhexyl salicylate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1O FMRHJJZUHUTGKE-UHFFFAOYSA-N 0.000 description 1
- 101710181403 Frizzled Proteins 0.000 description 1
- 101710140948 Frizzled-1 Proteins 0.000 description 1
- 102100021259 Frizzled-1 Human genes 0.000 description 1
- 101000967299 Homo sapiens Endothelin receptor type B Proteins 0.000 description 1
- 101000967336 Homo sapiens Endothelin-1 receptor Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 108010008364 Melanocortins Proteins 0.000 description 1
- 101800001751 Melanocyte-stimulating hormone alpha Proteins 0.000 description 1
- 102400000740 Melanocyte-stimulating hormone alpha Human genes 0.000 description 1
- 101710200814 Melanotropin alpha Proteins 0.000 description 1
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 206010040825 Skin depigmentation Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 229940069521 aloe extract Drugs 0.000 description 1
- RZOBLYBZQXQGFY-UHFFFAOYSA-N ammonium lactate Chemical compound [NH4+].CC(O)C([O-])=O RZOBLYBZQXQGFY-UHFFFAOYSA-N 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001166 anti-perspirative effect Effects 0.000 description 1
- 230000002421 anti-septic 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
- 239000003213 antiperspirant Substances 0.000 description 1
- XNEFYCZVKIDDMS-UHFFFAOYSA-N avobenzone Chemical group C1=CC(OC)=CC=C1C(=O)CC(=O)C1=CC=C(C(C)(C)C)C=C1 XNEFYCZVKIDDMS-UHFFFAOYSA-N 0.000 description 1
- 229960002255 azelaic acid Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 229940025250 camphora Drugs 0.000 description 1
- 239000010238 camphora Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 239000008406 cosmetic ingredient Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000002781 deodorant agent Substances 0.000 description 1
- 238000004332 deodorization Methods 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 229960002852 ellagic acid Drugs 0.000 description 1
- 235000004132 ellagic acid Nutrition 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- UVCJGUGAGLDPAA-UHFFFAOYSA-N ensulizole Chemical group N1C2=CC(S(=O)(=O)O)=CC=C2N=C1C1=CC=CC=C1 UVCJGUGAGLDPAA-UHFFFAOYSA-N 0.000 description 1
- 229960000655 ensulizole Drugs 0.000 description 1
- 150000002220 fluorenes Chemical class 0.000 description 1
- 229910021485 fumed silica Inorganic materials 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 210000004247 hand Anatomy 0.000 description 1
- 239000013003 healing agent Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960004881 homosalate Drugs 0.000 description 1
- 230000003810 hyperpigmentation Effects 0.000 description 1
- 208000000069 hyperpigmentation Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004611 light stabiliser Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 229940078752 magnesium ascorbyl phosphate Drugs 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000002865 melanocortin Substances 0.000 description 1
- 230000003101 melanogenic effect Effects 0.000 description 1
- 210000002780 melanosome Anatomy 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 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
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 229960003921 octisalate Drugs 0.000 description 1
- FMJSMJQBSVNSBF-UHFFFAOYSA-N octocrylene Chemical group C=1C=CC=CC=1C(=C(C#N)C(=O)OCC(CC)CCCC)C1=CC=CC=C1 FMJSMJQBSVNSBF-UHFFFAOYSA-N 0.000 description 1
- 229960000601 octocrylene Drugs 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 1
- 229960001173 oxybenzone Drugs 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000007761 roller coating Methods 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 238000005201 scrubbing Methods 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000037075 skin appearance Effects 0.000 description 1
- 230000035943 smell Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- HTJNEBVCZXHBNJ-XCTPRCOBSA-H trimagnesium;(2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one;diphosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.OC[C@H](O)[C@H]1OC(=O)C(O)=C1O HTJNEBVCZXHBNJ-XCTPRCOBSA-H 0.000 description 1
- KAKZBPTYRLMSJV-UHFFFAOYSA-N vinyl-ethylene Natural products C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/606—Nucleosides; Nucleotides; Nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Treatment And Processing Of Natural Fur Or Leather (AREA)
Abstract
本发明涉及皮肤美白组合物和皮肤美白方法。使用siRNA寡核苷酸实现皮肤美白，所述siRNA寡核苷酸能用比已知化学活性剂低得多的浓度实现这一点。
Description
技术领域
本发明涉及皮肤美白组合物和皮肤美白方法。
发明背景
已经报道了许多皮肤美白方法和组合物。已知用于皮肤美白的活性剂可以合成制备或可以使用或萃取自天然来源。这些活性剂通常可用于皮肤美白，以及用于治疗、预防或改善皮肤外观以对抗色素沉着过度、老年斑、瑕疵等。
肤色取决于黑色素在表皮细胞内的量、类型和分布。角化细胞是皮肤表皮中的主要细胞(群体的>90%)，而成纤维细胞位于真皮中，黑素细胞(总表皮细胞的~5%)存在于真皮:表皮接合处。这三种类型的细胞通过各种分泌的因子互相交流以调节皮肤色素沉着。
皮肤中的黑素细胞合成黑色素(生物聚合色素)并将其转移到相邻的角化细胞，以使黑色素分布在皮肤上层内。在专门的溶酶体相关的细胞器(被称作黑素体)内合成黑色素。肤色受若干因素影响，包括(a) 生成并转移到角化细胞中的黑色素的量和类型，和(b) 其随后在角化细胞内的并入、聚集和降解。调节皮肤色素沉着的其它因素包括由影响黑素细胞的角化细胞和成纤维细胞分泌的因子、来自供血的内分泌因子以及神经因子和炎症相关因子；影响皮肤色素沉着的外在因素包括紫外线(UV)辐射。已经报道了利用siRNA调节这些因素中的一些。
siRNA是短双链的小干扰RNA分子。大多数siRNA的长度为20-25个核苷酸。siRNA参与RNA干扰并在转录后调节(干扰 - 沉默)基因表达。可以使用适当的转染程序将合成siRNA引入细胞中并通常表现出瞬态效应。这导致相应的靶基因表达的基于序列互补的敲低。上述特征长度看起来使靶基因特异性最大化(超过非特异性效应)。当特定的靶基因是已知的时，整个过程包括选择性设计一些siRNA序列以靶向该基因的各种部分并凭实验测试，以确定该集合内最有效的siRNA序列(基因表达的最高抑制)。可以使用针对该基因的siRNA测试给定基因对于特定细胞现象的相关性。siRNA因此既充当基因功能研究中的检测工具，又充当调节基因表达并经此调节细胞生物学的技术手段。
例如在US 7 087 743、US 7 504 385和US 2007/0134188中公开了用于皮肤脱色素的寡核苷酸。在上述公开或任何其它公开文献中尚未公开掺入施加在皮肤上的组合物中的本发明中要求保护的寡核苷酸。
在EP1752536、EP2213738、WO2009/001359和WO2010/080452中报道了有可能用于医药用途的用于基因表达抑制的非常大量的siRNA分子。但是，它们都没有教导或指导本领域技术人员为皮肤美白益处而使用任何那些寡核苷酸用于在皮肤上施用。
因此本发明的一个目的是提供增强皮肤美白效力的新型寡核苷酸。
发明概述
根据本发明的第一方面，提供了包含siRNA的皮肤美白组合物，其包含
(a) 寡核苷酸，其包含选自下列之一的序列
它们的包含至少19个核苷酸的部分；和
(b) 化妆品可接受的载体；
其中寡核苷酸大小为19至30个核苷酸。
根据本发明的另一方面，提供了皮肤美白组合物，其包含：
(a) 包含寡核苷酸的siRNA，所述寡核苷酸包含选自下列的序列
它们的包含至少19个核苷酸的部分；和
(b) 化妆品可接受的载体，其选自乳液、洗液、霜、泡沫、凝胶、皂条、棒、面膜、棉片或贴剂；
其中寡核苷酸大小为19至30个核苷酸。
根据本发明的另一方面，提供了皮肤美白方法，其包括在皮肤上施加本发明的组合物。
发明详述
本领域普通技术人员在阅读下列详述和所附权利要求时容易看出这些和其它方面、特征和优点。为避免疑问，本发明的一个方面的任何特征可用于本发明的任何其它方面。词语“包含”意在表示“包括”但不一定“由...组成”或“由...构成”。换言之，所列步骤或选项不需要是穷举的。要指出，下列描述中给出的实例意在阐明本发明而无意将本发明限于这些实例本身。类似地，除非另行指明，所有百分比为重量/重量百分比。除了在实施例和对比例中或在另行明示之处外，本说明书和权利要求中指示材料量或反应条件、材料物理性质和/或用途的所有数值应被理解为用词语“大约”修饰。以“x至y”格式表示的数值范围被理解为包括x和y。当对特定特征而言，以“x至y”格式描述多个优选范围时，要理解的是，还考虑组合不同端点的所有范围。
本文所用的“皮肤美白组合物”意在包括局部施加到皮肤上以增白天然肤色的组合物。这种组合物通常可分类为免洗或洗除型，并包括施加到人体上以还有改善外观、清洁、气味控制或一般美观的任何产品。本发明的组合物可以是液体、洗液、霜、泡沫、磨砂膏、凝胶、皂条或化妆水形式，或用工具或经面膜、棉片或贴剂施加。这种组合物的非限制性实例包括免洗护肤液、霜、止汗剂、除臭剂、粉底和洗除型洗发水、护发素、沐浴凝胶和皂条。本发明的组合物优选是免洗组合物。本文所用的“皮肤”意在包括面部和身体(例如颈、胸、背、手臂、腋下、手、腿、臀部和头皮)上的皮肤，尤其是其暴露在阳光下的部分。
本发明的组合物包含配制到用于皮肤美白用途的化妆品可接受的基质中的siRNA(双链核苷酸)，其包含长度为19至30个核苷酸的所选寡核苷酸。用于本发明的寡核苷酸是在这一领域中的广泛研究后选择的，下面描述选择过程。
皮肤中存在的角化细胞、黑素细胞和成纤维细胞通过各种分泌的因子互相交流以调节皮肤色素沉着。本发明人已经研究了这些因子中的一些，仔细挑选以使它们对黑素生成的影响最大化，即干细胞因子(SCF)、内皮素(EDN)、α-黑素细胞刺激激素(α-MSH)和Wnt，它们分别结合到它们的同源受体c-Kit酪氨酸激酶、内皮素受体A和B(EDNRA和EDNRB)、黑皮质素1和Frizzled 1(Fz1)上。这样的相互作用引发调节皮肤色素沉着的多种下游信号传导通路。本发明人已经分析了最可能在基因表达水平下抑制所述受体的核酸序列并得出可能调节皮肤美白的大量这样的序列。然后使用黑色素含量体外检测法实验测试这些大量的寡核苷酸序列(存在于双链siRNA中)作为皮肤美白剂的潜力并获得本发明，其包括利用十种这样的寡核苷酸提供皮肤美白益处。
这十种寡核苷酸是：
它们的包含至少19个核苷酸的部分。
根据一个优选方面，包含至少19个核苷酸的部分是连续核苷酸(contiguous nucleotides)。
根据本发明，寡核苷酸大小为19至30个核苷酸长。用于提供本发明的益处的siRNA可以小至19个核苷酸长，在这种情况下，所需核苷酸可以是本发明中要求保护的序列(1)至(10)的任何部分。或者，所需寡核苷酸可以长达30个核苷酸长，其包含这十个序列中的任一整个，并另外包含连接在一个或两个末端上的几个核苷酸。
根据本发明的一个优选方面，该寡核苷酸为至少20个核苷酸长，优选至少22个，更优选至少25个核苷酸长。根据再一优选方面，该寡核苷酸为最多30个，更优选最多27个，再更优选最多25个核苷酸长。该寡核苷酸最优选为19至25个核苷酸长。根据本发明的再一优选方面，该寡核苷酸选自
该寡核苷酸优选是下列之一
该寡核苷酸更优选是下列之一
使用其中寡核苷酸的糖组分已化学修饰的siRNA在本发明的范围内。
根据本发明的一个优选方面，提供了皮肤美白组合物，其包含：
(a) 包含寡核苷酸的siRNA，所述寡核苷酸包含选自下列的序列
它们的包含至少19个核苷酸的部分；和
(b) 化妆品可接受的载体；
其中寡核苷酸大小为19至30个核苷酸。
根据本发明的再一优选方面，提供了皮肤美白组合物，其包含：
(a) 包含寡核苷酸的siRNA，所述寡核苷酸包含选自下列的序列
它们的包含至少20个核苷酸的部分；和
(b) 化妆品可接受的载体；
其中寡核苷酸大小为20至30个核苷酸。
在上述优选方面中，该寡核苷酸为至少20个核苷酸长，优选至少22，更优选至少25个核苷酸长。
根据本发明的另一方面，提供了皮肤美白组合物，其包含：
(a) 包含寡核苷酸的siRNA，所述寡核苷酸包含选自下列的序列
它们的包含至少19个核苷酸的部分；和
(b) 化妆品可接受的载体，其选自乳液、洗液、霜、泡沫、凝胶、皂条、棒、面膜、棉片或贴剂；
其中寡核苷酸大小为19至30个核苷酸。
该寡核苷酸优选以更安全和有效的量存在于该组合物中以便能明显改进皮肤美白效力。该寡核苷酸更优选以该组合物的0.00001至1重量%，更优选0.0001至0.01重量%存在。
该化妆品可接受的载体优选是乳液、洗液、霜、泡沫、凝胶、皂条、棒、面膜、棉片或贴剂，更优选是霜、凝胶或洗液。
当本发明的组合物是霜时，其优选包含3至25%脂肪酸。当本发明的组合物是洗液时，其优选包含1至20%脂肪酸。更优选的形式是霜，再更优选是雪花膏。雪花膏基质是包含1至25%，更优选5至20%脂肪酸的基质。该脂肪酸可以是饱和或不饱和的脂肪酸。该基质优选包含0.1至10%，更优选0.1至3%皂。C12至C20脂肪酸在雪花膏基质中尤其优选，再更优选的是C14至C18脂肪酸。在霜中，脂肪酸优选基本是硬脂酸和棕榈酸的混合物。雪花膏基质中的皂包括脂肪酸的碱金属盐，如钠或钾盐。该皂优选是脂肪酸混合物的钾盐。雪花膏基质中的脂肪酸通常使用hystric酸(其基本(通常大约90至95%)是硬脂酸和棕榈酸的混合物)制备。因此，包括hystric酸及其皂以制备雪花膏基质在本发明的范围内。该化妆品可接受的基质通常为该组合物的10至99.9重量%，优选50至99重量%。该化妆品可接受的基质优选包括水。优选以该组合物的35至90重量%，更优选50至85重量%，再更优选50至80重量%包括水。
本发明的组合物优选包含UV-A和/或UV-B防晒剂。这两种类型的有机防晒剂通常可获自下列主要类别：二苯甲酮、邻氨基苯甲酸酯、二苯甲酰甲烷、水杨酸酯、肉桂酸酯、樟脑和三嗪。
本发明的组合物优选包含UV-A防晒剂，其是二苯甲酰甲烷或其衍生物。最优选的二苯甲酰甲烷衍生物是4-叔丁基-4'-甲氧基二苯甲酰甲烷。
在本发明的组合物中优选包括油溶性的UV-B有机防晒剂。油溶性的UV-B防晒剂优选选自肉桂酸、水杨酸、二苯基水杨酸或其衍生物。可购得并可用于包含在本发明的组合物中的几种优选的油溶性UV-B防晒剂是OctisalateTM、HomosalateTM、NeoHelipanTM、OctocryleneTM、OxybenzoneTM或Parsol MCXTM。或者，在本发明的组合物中优选包括水溶性有机UVB防晒剂。优选的水溶性有机UVB防晒剂是苯基苯并咪唑磺酸。
本发明的组合物优选包含占该组合物总重量的按重量计0.1至5%，更优选0.2至5%，再更优选0.4至3%的UV-A和/或UV-B防晒剂，并包括其中包含的所有范围。
在本发明的组合物中可以包括光稳定剂。合适的光稳定化合物是二苯基丙烯酸酯、亚苄基樟脑、萘二甲酸酯(napthalate)、三嗪、芴或二芳基丁二烯类型的。
在本发明中可优选使用其它可用的防晒剂，例如无机防晒剂。这些包括例如氧化锌、氧化铁、二氧化硅如锻制二氧化硅，或二氧化钛。优选并入本发明的组合物中的防晒剂的总量为该组合物的0.1至5重量%。
本发明的组合物可另外包含皮肤美白剂。该皮肤美白剂优选选自维生素B3化合物或其衍生物，例如烟碱酸、烟酸、烟酰胺或其它公知的皮肤美白剂，例如芦荟提取物、乳酸铵、壬二酸、曲酸、柠檬酸酯、鞣花酸、乙醇酸、绿茶提取物、氢醌、柠檬提取物、亚油酸、抗坏血酸磷酸镁、维生素如维生素B6、维生素B12、维生素C、维生素A、二羧酸、间苯二酚衍生物、羟基羧酸如乳酸和它们的盐，例如乳酸钠，及其混合物。维生素B3化合物或其衍生物，例如烟碱酸、烟酸、烟酰胺是根据本发明更优选的皮肤美白剂，最优选的是烟酰胺。烟酰胺在使用时优选以该组合物的0.1至10重量%，更优选0.2至5重量%范围的量存在。
本发明的组合物还可包含其它稀释剂。稀释剂充当该组合物中存在的其它材料的分散剂或载体，以便在将该组合物施加到皮肤上时利于它们的分布。除了水以外的稀释剂可包括液体或固体润肤剂、溶剂、保湿剂、增稠剂和粉末。
本发明的组合物可包含常规除臭剂基质作为化妆品可接受的载体。除臭剂是指为个人除臭益处使用的、例如施加在腋下或任何其它区域的、可能含有或不含止汗活性剂的在棒、滚涂或推进剂介质中的产品。
除臭剂组合物通常可以是紧实固体、软固体、凝胶、霜和液体形式并使用适合该组合物的物理特性的涂施器分配。
本发明的组合物可包含多种其它任选组分。全文经此引用并入本文的CTFA Cosmetic Ingredient Handbook, 第2版, 1992描述了适用在本发明的组合物中的在护肤工业中常用的多种非限制性化妆品和药物成分。实例包括：抗氧化剂、粘合剂、生物添加剂、缓冲剂、着色剂、增稠剂、聚合物、收敛剂、香料、湿润剂、乳浊剂、调理剂、去角质剂、pH调节剂、防腐剂、天然提取物、香精油、皮肤感觉剂(skin sensates)、皮肤舒缓剂和皮肤愈合剂。
根据本发明的另一方面，提供了皮肤美白方法，其包括将本发明的皮肤美白组合物施加到皮肤的预期表面上的步骤。
本发明的组合物针对化妆品和护肤用途，因此优选不用于治疗/医疗用途。
现在借助下列非限制性实施例进一步描述本发明。
实施例
实施例1至10：用于量化siRNA序列的皮肤美白效力的黑色素含量检测
合成制备十种siRNA双链，其中一个链具有如下给出的寡核苷酸，并用来使用黑色素含量体外检测法评估作为皮肤美白剂的潜力。本领域技术人员清楚的是，规定单链就足以完全定义该双链siRNA。该体外检测如下进行：
检测包含下列寡核苷酸序列的siRNA：
。
siRNA转染
将原代人黑素细胞培养24小时。在培养基中用Mirus Trans IT-TKO转染试剂和双链体寡聚物转染细胞。细胞在增湿的CO2培养箱中在37℃下培养并在转染后96-144小时收获以进行黑色素含量和存活力检测。
存活力：在转染96、120、144或168小时后，除去培养基并将中性红(在黑素细胞培养基中50μg/ml)添加到细胞中并在CO2培养箱中在37℃下培养3小时。在培养结束时，细胞用1 x磷酸盐缓冲溶液(PBS)洗涤，使用解吸溶液(乙醇:水:冰醋酸，50:49:1)提取染料，并在540纳米下测量吸光度。
黑色素含量：在转染96、120、144或168小时后，除去培养基并将细胞溶解在200微升10% DMSO/1N NaOH中。在60℃下1小时后，在400纳米下测量吸光度。
计算：黑色素含量表示为与扰乱(scramble)处理细胞相比的%黑色素含量。
进行实验，关于黑色素含量的数据(作为对照样品的百分比)作为3个读数的平均值概括在表1中。已知曲酸在72小时内作用完全。
表1
| 实施例 | 浓度 (nM) | 时间点(小时) | %对照 黑色素 | 标准偏差 |
| SEQ ID:1 | 20 | 144 | 76 | 10 |
| SEQ ID:2 | 20 | 144 | 75 | 3 |
| SEQ ID:3 | 20 | 144 | 80 | 8 |
| SEQ ID:4 | 20 | 96 | 62 | 1 |
| SEQ ID:5 | 20 | 144 | 77 | 5 |
| SEQ ID:6 | 50 | 168 | 81 | 4 |
| SEQ ID:7 | 50 | 168 | 85 | 4 |
| SEQ ID:8 | 20 | 144 | 81 | 8 |
| SEQ ID:9 | 20 | 144 | 84 | 15 |
| SEQ ID:10 | 10 | 120 | 83 | 5 |
| 曲酸(对照) | 105 | 72 | 76 | 7 |
表1中的数据表明，本发明的组合物(SEQ ID:1至SEQ ID:10)提供良好的黑色素含量降低，与公知活性剂之一，即曲酸相当。本发明的优点在于siRNA可以以量级低于该化学活性剂的浓度使用。
Claims (7)
1.皮肤美白组合物，其包含：
(a) 包含寡核苷酸的siRNA，所述寡核苷酸包含选自下列的序列
它们的包含至少19个核苷酸的部分；和
(b) 化妆品可接受的载体；
其中寡核苷酸大小为19至30个核苷酸。
2.如权利要求1中所述的皮肤美白组合物，其包含：
(a) 包含寡核苷酸的siRNA，所述寡核苷酸包含选自下列的序列
它们的包含至少19个核苷酸的部分；和
(b) 化妆品可接受的载体；
其中寡核苷酸大小为19至30个核苷酸。
3.如权利要求1中所述的皮肤美白组合物，其包含：
(a) 包含寡核苷酸的siRNA，所述寡核苷酸包含选自下列的序列
它们的包含至少20个核苷酸的部分；和
(b) 化妆品可接受的载体；
其中寡核苷酸大小为20至30个核苷酸。
4.皮肤美白组合物，其包含：
(a) 包含寡核苷酸的siRNA，所述寡核苷酸包含选自下列的序列
它们的包含至少19个核苷酸的部分；和
(b) 化妆品可接受的载体，其选自乳液、洗液、霜、泡沫、凝胶、皂条、棒、面膜、棉片或贴剂；
其中寡核苷酸大小为19至30个核苷酸。
5.如前述权利要求任一项中所述的皮肤美白组合物，其中所述化妆品可接受的载体是霜、凝胶或洗液。
6.如前述权利要求任一项中所述的皮肤美白组合物，其中所述siRNA以所述组合物的0.00001至1重量%存在。
7.皮肤美白方法，其包括将前述权利要求任一项中所述的皮肤美白组合物施加到皮肤的预期表面上的步骤。
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN390/MUM/2012 | 2012-02-13 | ||
| IN390MU2012 | 2012-02-13 | ||
| EP12163547 | 2012-04-10 | ||
| EP12163547.8 | 2012-04-10 | ||
| PCT/EP2013/052211 WO2013120726A2 (en) | 2012-02-13 | 2013-02-05 | A skin lightening composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104105473A true CN104105473A (zh) | 2014-10-15 |
| CN104105473B CN104105473B (zh) | 2017-09-12 |
Family
ID=47666139
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380009238.4A Expired - Fee Related CN104105473B (zh) | 2012-02-13 | 2013-02-05 | 皮肤美白组合物 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9295631B2 (zh) |
| EP (1) | EP2814455B1 (zh) |
| CN (1) | CN104105473B (zh) |
| BR (1) | BR112014018809A8 (zh) |
| EA (1) | EA201400911A1 (zh) |
| WO (1) | WO2013120726A2 (zh) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3270881B1 (en) | 2015-03-20 | 2018-12-26 | Unilever PLC, a company registered in England and Wales under company no. 41424 of | Antiperspirant composition |
| KR102552848B1 (ko) * | 2016-08-29 | 2023-07-06 | 더 리전츠 오브 더 유니버시티 오브 캘리포니아 | 피부 치료를 위한 이온성 약제에 기초한 국소 제형 |
| WO2024104663A1 (en) | 2022-11-16 | 2024-05-23 | Unilever Ip Holdings B.V. | Method of reducing malodour |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2420119A (en) * | 2004-11-15 | 2006-05-17 | Secr Defence | RNA interference molecules targeting human Keap1 |
| EP1752536A1 (en) * | 2004-05-11 | 2007-02-14 | RNAi Co., Ltd. | Polynucleotide causing rna interfere and method of regulating gene expression with the use of the same |
| WO2009001359A2 (en) * | 2007-06-27 | 2008-12-31 | Quark Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of pro-apoptotic genes |
| WO2010080452A2 (en) * | 2008-12-18 | 2010-07-15 | Quark Pharmaceuticals, Inc. | siRNA COMPOUNDS AND METHODS OF USE THEREOF |
| EP2213738A2 (en) * | 2002-11-14 | 2010-08-04 | Dharmacon, Inc. | siRNA molecules targeting Bcl-2 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08140699A (ja) | 1994-11-22 | 1996-06-04 | Pola Chem Ind Inc | チロシナーゼｍＲＮＡ量の測定法 |
| WO1997031012A1 (en) | 1996-02-22 | 1997-08-28 | The Regents Of The University Of Michigan | Gene specific universal mammalian sequence-tagged sites |
| FR2804960B1 (fr) | 2000-02-11 | 2005-06-24 | Lvmh Rech | Nouveaux oligonucleotides et utilisation d'oligonucleotides modulant l'expression de la tyrosinase et de la tyrosinase- related-protein 1 comme agents depigmentants |
| US7504385B2 (en) | 2003-12-17 | 2009-03-17 | Avon Products, Inc. | si-RNA-mediated gene silencing technology to inhibit tyrosinase and reduce pigmentation |
| US8119791B2 (en) | 2003-12-17 | 2012-02-21 | Avon Products, Inc. | si-RNA-mediated gene silencing technology to inhibit tyrosinase and reduce pigmentation |
| FR2890859B1 (fr) | 2005-09-21 | 2012-12-21 | Oreal | Oligonucleotide d'arn double brin inhibant l'expression de la tyrosinase |
| FR2894582B1 (fr) | 2005-12-12 | 2008-02-22 | Fabre Pierre Dermo Cosmetique | Sirna anti myosine va et depigmentation de la peau |
| US8735567B2 (en) | 2007-11-06 | 2014-05-27 | Patrick Y. Lu | Multi-targeted RNAi therapeutics for scarless wound healing of skin |
| FR2930151A1 (fr) | 2008-04-22 | 2009-10-23 | Centre Nat Rech Scient | Nouvelles compositions inhibant la melanogenese et leurs utilisations |
| FR2930152A1 (fr) | 2008-04-22 | 2009-10-23 | Centre Nat Rech Scient | Nouvelles compositions inhibant la melanogenese et leurs utilisations |
| WO2009141541A2 (fr) | 2008-04-22 | 2009-11-26 | Centre National De La Recherche Scientifique | Nouvelles compositions inhibant la melanogenese et leurs utilisations |
| ES2334092B1 (es) | 2008-07-02 | 2011-01-24 | Proyecto De Biomedicina Cima, S.L. | Agentes antiangiogenicos. |
-
2013
- 2013-02-05 WO PCT/EP2013/052211 patent/WO2013120726A2/en active Application Filing
- 2013-02-05 US US14/376,938 patent/US9295631B2/en not_active Expired - Fee Related
- 2013-02-05 EA EA201400911A patent/EA201400911A1/ru unknown
- 2013-02-05 BR BR112014018809A patent/BR112014018809A8/pt not_active IP Right Cessation
- 2013-02-05 CN CN201380009238.4A patent/CN104105473B/zh not_active Expired - Fee Related
- 2013-02-05 EP EP13702804.9A patent/EP2814455B1/en not_active Not-in-force
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2213738A2 (en) * | 2002-11-14 | 2010-08-04 | Dharmacon, Inc. | siRNA molecules targeting Bcl-2 |
| EP1752536A1 (en) * | 2004-05-11 | 2007-02-14 | RNAi Co., Ltd. | Polynucleotide causing rna interfere and method of regulating gene expression with the use of the same |
| GB2420119A (en) * | 2004-11-15 | 2006-05-17 | Secr Defence | RNA interference molecules targeting human Keap1 |
| WO2009001359A2 (en) * | 2007-06-27 | 2008-12-31 | Quark Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of pro-apoptotic genes |
| WO2010080452A2 (en) * | 2008-12-18 | 2010-07-15 | Quark Pharmaceuticals, Inc. | siRNA COMPOUNDS AND METHODS OF USE THEREOF |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013120726A2 (en) | 2013-08-22 |
| WO2013120726A3 (en) | 2014-05-01 |
| CN104105473B (zh) | 2017-09-12 |
| US20150157547A1 (en) | 2015-06-11 |
| EP2814455B1 (en) | 2017-07-19 |
| US9295631B2 (en) | 2016-03-29 |
| EP2814455A2 (en) | 2014-12-24 |
| BR112014018809A8 (pt) | 2017-07-11 |
| BR112014018809A2 (zh) | 2017-06-20 |
| EA201400911A1 (ru) | 2014-11-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103479694B (zh) | 含有人参的花或人参的种子提取物的皮肤外用剂组合物 | |
| CN103889397B (zh) | 含有绿茶成分的化妆品组合物 | |
| CN103417391B (zh) | 亮肤的方法 | |
| CN101810552A (zh) | 用于治疗皮肤老化迹象的组合物和方法 | |
| CN102821742A (zh) | 黑色素抑制剂及含有该抑制剂的化妆品组合物 | |
| CN103201625A (zh) | 调节涉及黑素生成的肾上腺素受体基因表达的筛选方法 | |
| US20160317418A1 (en) | Method of improving the appearance of skin and compositions therefor | |
| CA3011834C (en) | Skin cosmetic composition comprising saccharin, maltol, and theobromine | |
| KR20200002008A (ko) | 피부 유래 스트렙토코쿠스 살리바리우스 ｓｂｋ４ 신균주 및 이를 이용한 기능성 화장료 조성물 | |
| CN103002863A (zh) | 利用多种活性物质改善色素沉着斑点外观的方法 | |
| CN104105473A (zh) | 皮肤美白组合物 | |
| CN104207972A (zh) | 包含苦木裂榄木提取物的组合物 | |
| KR102403451B1 (ko) | 펩타이드 복합체 및 천연 복합 추출물을 함유하는 다기능성 화장료 조성물 | |
| CN107427434A (zh) | 用于诱导促进细胞复壮的包含染料木黄酮或表没食子儿茶素没食子酸酯的组合物 | |
| KR101320262B1 (ko) | 형질 전환 세포주와 백반증 마우스를 이용한 백모 방지 물질 스크리닝 방법 및 그 백모 방지 물질을 함유하는 백모방지용 조성물 | |
| CN104411288B (zh) | 1‑羟基3,5‑双(4’羟基苯乙烯基)苯的局部施用 | |
| US10463588B2 (en) | Cosmetic composition for anti-aging or alleviating skin redness, and medicinal composition for preventing and treating skin inflammatory diseases, containing compound inducing increase in expression of adiponectin | |
| KR20240031906A (ko) | 뽕나무 유래 화합물을 유효성분으로 포함하는 피부 질환 예방 또는 개선용 화장료 조성물 | |
| JP2024134554A (ja) | 毛髪ケア活性剤 | |
| KR20220065439A (ko) | 트리코데르마 아트로비리데 배양 추출물을 포함하는 미백 화장료 조성물 | |
| KR101320188B1 (ko) | 형질 전환 세포주와 백반증 마우스를 이용한 백모 방지 물질 스크리닝 방법 및 그 백모 방지 물질을 함유하는 백모방지용 조성물 | |
| KR20220048365A (ko) | 아스페르길루스 푸미가투스 sw-1 배양 추출물을 포함하는 미백 화장료 조성물 | |
| KR20200034084A (ko) | 마크루린을 포함하는 피부 미백용 조성물 | |
| Donat | Innovative development in even skin tone: ingredients |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210830 Address after: Rotterdam Patentee after: Unilever Intellectual Property Holdings Ltd. Address before: Rotterdam Patentee before: Unilever Nederland B.V. |
|
| TR01 | Transfer of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170912 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |