CN114375291B - 用于亮肤的新型化合物 - Google Patents
用于亮肤的新型化合物 Download PDFInfo
- Publication number
- CN114375291B CN114375291B CN202080061076.9A CN202080061076A CN114375291B CN 114375291 B CN114375291 B CN 114375291B CN 202080061076 A CN202080061076 A CN 202080061076A CN 114375291 B CN114375291 B CN 114375291B
- Authority
- CN
- China
- Prior art keywords
- skin
- acid
- compounds
- cyclohexyl
- oxygen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 45
- 206010040829 Skin discolouration Diseases 0.000 title abstract description 6
- 239000000203 mixture Substances 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 17
- 239000001301 oxygen Substances 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 239000000516 sunscreening agent Substances 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 12
- ULQISTXYYBZJSJ-UHFFFAOYSA-N 12-hydroxyoctadecanoic acid Chemical compound CCCCCCC(O)CCCCCCCCCCC(O)=O ULQISTXYYBZJSJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000007854 depigmenting agent Substances 0.000 claims description 8
- 239000002537 cosmetic Substances 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 208000003351 Melanosis Diseases 0.000 claims description 6
- 206010014970 Ephelides Diseases 0.000 claims description 5
- 150000005207 1,3-dihydroxybenzenes Chemical class 0.000 claims description 4
- 229940114072 12-hydroxystearic acid Drugs 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 2
- 235000005152 nicotinamide Nutrition 0.000 claims description 2
- 239000011570 nicotinamide Substances 0.000 claims description 2
- 229960003966 nicotinamide Drugs 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 208000037259 Amyloid Plaque Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 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 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- -1 halogen salts Chemical class 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 12
- 230000000475 sunscreen effect Effects 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 206010040865 Skin hyperpigmentation Diseases 0.000 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 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 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000001603 reducing effect Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 229940060184 oil ingredients Drugs 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- NTQVODZUQIATFS-WAUHAFJUSA-N (2s)-2-[[(2s)-6-amino-2-[[2-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-amino-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-3-methylbutanoic acid Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O NTQVODZUQIATFS-WAUHAFJUSA-N 0.000 description 3
- WDANSDASCKBVKH-UHFFFAOYSA-N 4-propan-2-yloxybenzaldehyde Chemical compound CC(C)OC1=CC=C(C=O)C=C1 WDANSDASCKBVKH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108010024636 Glutathione Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WYWZRNAHINYAEF-UHFFFAOYSA-N Padimate O Chemical compound CCCCC(CC)COC(=O)C1=CC=C(N(C)C)C=C1 WYWZRNAHINYAEF-UHFFFAOYSA-N 0.000 description 3
- 102100037132 Proteinase-activated receptor 2 Human genes 0.000 description 3
- 101710121435 Proteinase-activated receptor 2 Proteins 0.000 description 3
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 3
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- XNEFYCZVKIDDMS-UHFFFAOYSA-N avobenzone Chemical compound C1=CC(OC)=CC=C1C(=O)CC(=O)C1=CC=C(C(C)(C)C)C=C1 XNEFYCZVKIDDMS-UHFFFAOYSA-N 0.000 description 3
- 150000003939 benzylamines Chemical class 0.000 description 3
- PVHMFYAZPKLTIA-UHFFFAOYSA-N cyclohexyl-(4-propan-2-yloxyphenyl)methanol Chemical compound C1=CC(OC(C)C)=CC=C1C(O)C1CCCCC1 PVHMFYAZPKLTIA-UHFFFAOYSA-N 0.000 description 3
- NZZIMKJIVMHWJC-UHFFFAOYSA-N dibenzoylmethane Chemical class C=1C=CC=CC=1C(=O)CC(=O)C1=CC=CC=C1 NZZIMKJIVMHWJC-UHFFFAOYSA-N 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 229960003180 glutathione Drugs 0.000 description 3
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 230000036564 melanin content Effects 0.000 description 3
- FMJSMJQBSVNSBF-UHFFFAOYSA-N octocrylene Chemical compound C=1C=CC=CC=1C(=C(C#N)C(=O)OCC(CC)CCCC)C1=CC=CC=C1 FMJSMJQBSVNSBF-UHFFFAOYSA-N 0.000 description 3
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000006268 reductive amination reaction Methods 0.000 description 3
- 238000005556 structure-activity relationship Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 229910021642 ultra pure water Inorganic materials 0.000 description 3
- 239000012498 ultrapure water Substances 0.000 description 3
- RNBLBVHLGUYTTC-UHFFFAOYSA-N 1-[chloro(cyclohexyl)methyl]-4-propan-2-yloxybenzene Chemical compound C1=CC(OC(C)C)=CC=C1C(Cl)C1CCCCC1 RNBLBVHLGUYTTC-UHFFFAOYSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- WFJIVOKAWHGMBH-UHFFFAOYSA-N 4-hexylbenzene-1,3-diol Chemical compound CCCCCCC1=CC=C(O)C=C1O WFJIVOKAWHGMBH-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
- ATJPSTFFKCDOEB-UHFFFAOYSA-N CC(C)OC1=CC=C(C=C1)C(C2CCCCC2)NC3CCOCC3 Chemical compound CC(C)OC1=CC=C(C=C1)C(C2CCCCC2)NC3CCOCC3 ATJPSTFFKCDOEB-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-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
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 208000012641 Pigmentation disease Diseases 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 108091022863 bile acid binding Proteins 0.000 description 2
- 102000030904 bile acid binding Human genes 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- 239000003974 emollient agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 229910021485 fumed silica Inorganic materials 0.000 description 2
- 229960003258 hexylresorcinol Drugs 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 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 2
- 208000031066 hyperpigmentation of the skin Diseases 0.000 description 2
- BTFJIXJJCSYFAL-UHFFFAOYSA-N icosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 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
- 229960004705 kojic acid Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 2
- 125000000627 niacin group Chemical class 0.000 description 2
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-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
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000019612 pigmentation Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 229940114930 potassium stearate Drugs 0.000 description 2
- ANBFRLKBEIFNQU-UHFFFAOYSA-M potassium;octadecanoate Chemical compound [K+].CCCCCCCCCCCCCCCCCC([O-])=O ANBFRLKBEIFNQU-UHFFFAOYSA-M 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 2
- 238000011002 quantification 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
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 229960004274 stearic acid Drugs 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 235000019158 vitamin B6 Nutrition 0.000 description 2
- 239000011726 vitamin B6 Substances 0.000 description 2
- 229940011671 vitamin b6 Drugs 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- PDHSAQOQVUXZGQ-JKSUJKDBSA-N (2r,3s)-2-(3,4-dihydroxyphenyl)-3-methoxy-3,4-dihydro-2h-chromene-5,7-diol Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2OC)=CC=C(O)C(O)=C1 PDHSAQOQVUXZGQ-JKSUJKDBSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-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
- QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 description 1
- LDKBTTCUTLPCOC-UHFFFAOYSA-N 1,2-diphenylpiperazine Chemical compound C1NCCN(C=2C=CC=CC=2)C1C1=CC=CC=C1 LDKBTTCUTLPCOC-UHFFFAOYSA-N 0.000 description 1
- VEAFKIYNHVBNIP-UHFFFAOYSA-N 1,3-Diphenylpropane Chemical class C=1C=CC=CC=1CCCC1=CC=CC=C1 VEAFKIYNHVBNIP-UHFFFAOYSA-N 0.000 description 1
- LALVCWMSKLEQMK-UHFFFAOYSA-N 1-phenyl-3-(4-propan-2-ylphenyl)propane-1,3-dione Chemical compound C1=CC(C(C)C)=CC=C1C(=O)CC(=O)C1=CC=CC=C1 LALVCWMSKLEQMK-UHFFFAOYSA-N 0.000 description 1
- LGEZTMRIZWCDLW-UHFFFAOYSA-N 14-methylpentadecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC(C)C LGEZTMRIZWCDLW-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VNXWANZMRATDQM-UHFFFAOYSA-N 2-(2-phenylethyl)benzene-1,3-diol Chemical compound OC1=CC=CC(O)=C1CCC1=CC=CC=C1 VNXWANZMRATDQM-UHFFFAOYSA-N 0.000 description 1
- FLPJVCMIKUWSDR-UHFFFAOYSA-N 2-(4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1 FLPJVCMIKUWSDR-UHFFFAOYSA-N 0.000 description 1
- QHDDZRCEINZAMT-UHFFFAOYSA-N 2-[4-(dimethylamino)phenyl]-1,3-benzoxazole-5-sulfonic acid Chemical compound C1=CC(N(C)C)=CC=C1C1=NC2=CC(S(O)(=O)=O)=CC=C2O1 QHDDZRCEINZAMT-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-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
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- JKRDADVRIYVCCY-UHFFFAOYSA-N 2-hydroxyoctanoic acid Chemical compound CCCCCCC(O)C(O)=O JKRDADVRIYVCCY-UHFFFAOYSA-N 0.000 description 1
- OJIBJRXMHVZPLV-UHFFFAOYSA-N 2-methylpropyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(C)C OJIBJRXMHVZPLV-UHFFFAOYSA-N 0.000 description 1
- OCLCRYNZYRSURW-UHFFFAOYSA-N 2-phenyl-2,3-dihydroinden-1-one Chemical class C1C2=CC=CC=C2C(=O)C1C1=CC=CC=C1 OCLCRYNZYRSURW-UHFFFAOYSA-N 0.000 description 1
- GDTSJMKGXGJFGQ-UHFFFAOYSA-N 3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound O1B([O-])OB2OB([O-])OB1O2 GDTSJMKGXGJFGQ-UHFFFAOYSA-N 0.000 description 1
- XNGHLOYNBBJSOM-UHFFFAOYSA-N 3-ethyloctan-3-yl naphthalene-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC(CC)(CC)CCCCC)=CC=CC2=C1 XNGHLOYNBBJSOM-UHFFFAOYSA-N 0.000 description 1
- GNRKGNLBYVFKKD-UHFFFAOYSA-N 4-(1,3-dithian-2-yl)phenol Chemical compound C1=CC(O)=CC=C1C1SCCCS1 GNRKGNLBYVFKKD-UHFFFAOYSA-N 0.000 description 1
- YDIYEOMDOWUDTJ-UHFFFAOYSA-N 4-(dimethylamino)benzoic acid Chemical compound CN(C)C1=CC=C(C(O)=O)C=C1 YDIYEOMDOWUDTJ-UHFFFAOYSA-N 0.000 description 1
- GFBCWCDNXDKFRH-UHFFFAOYSA-N 4-(oxan-2-yloxy)phenol Chemical compound C1=CC(O)=CC=C1OC1OCCCC1 GFBCWCDNXDKFRH-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- KTKGSSUXUIUZDA-UHFFFAOYSA-N 4-hydroxy-5-methyloxolan-3-one Chemical compound CC1OCC(=O)C1O KTKGSSUXUIUZDA-UHFFFAOYSA-N 0.000 description 1
- 150000005422 4-hydroxybenzoic acid derivatives Chemical class 0.000 description 1
- AMEMLELAMQEAIA-UHFFFAOYSA-N 6-(tert-butyl)thieno[3,2-d]pyrimidin-4(3H)-one Chemical compound N1C=NC(=O)C2=C1C=C(C(C)(C)C)S2 AMEMLELAMQEAIA-UHFFFAOYSA-N 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004251 Ammonium lactate Substances 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 206010008570 Chloasma Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical class [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 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
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- HDIFHQMREAYYJW-XGXNLDPDSA-N Glyceryl Ricinoleate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC(=O)OCC(O)CO HDIFHQMREAYYJW-XGXNLDPDSA-N 0.000 description 1
- CMBYOWLFQAFZCP-UHFFFAOYSA-N Hexyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCCCCC CMBYOWLFQAFZCP-UHFFFAOYSA-N 0.000 description 1
- 229940115480 Histamine H3 receptor antagonist Drugs 0.000 description 1
- 101001016833 Homo sapiens Histamine H3 receptor Proteins 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 108010030545 N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide Proteins 0.000 description 1
- 102000004129 N-Type Calcium Channels Human genes 0.000 description 1
- 108090000699 N-Type Calcium Channels Proteins 0.000 description 1
- 241000772415 Neovison vison Species 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- SBLKVIQSIHEQOF-UPHRSURJSA-N Octadec-9-ene-1,18-dioic-acid Chemical compound OC(=O)CCCCCCC\C=C/CCCCCCCC(O)=O SBLKVIQSIHEQOF-UPHRSURJSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 240000005373 Panax quinquefolius Species 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229940118430 Protease-activated receptor-2 antagonist Drugs 0.000 description 1
- 235000019484 Rapeseed oil Nutrition 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 1
- 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229940122388 Thrombin inhibitor Drugs 0.000 description 1
- LCKIEQZJEYYRIY-UHFFFAOYSA-N Titanium ion Chemical compound [Ti+4] LCKIEQZJEYYRIY-UHFFFAOYSA-N 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108060005989 Tryptase Proteins 0.000 description 1
- 102000001400 Tryptase Human genes 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- HEAHZSUCFKFERC-IWGRKNQJSA-N [(2e)-2-[[4-[(e)-[7,7-dimethyl-3-oxo-4-(sulfomethyl)-2-bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical group CC1(C)C2CCC1(CS(O)(=O)=O)C(=O)\C2=C\C(C=C1)=CC=C1\C=C/1C(=O)C2(CS(O)(=O)=O)CCC\1C2(C)C HEAHZSUCFKFERC-IWGRKNQJSA-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
- OLMIXROZPWAJNJ-UHFFFAOYSA-N [4-(1,3-dithian-2-yl)phenyl] acetate Chemical compound C1=CC(OC(=O)C)=CC=C1C1SCCCS1 OLMIXROZPWAJNJ-UHFFFAOYSA-N 0.000 description 1
- GANNOFFDYMSBSZ-UHFFFAOYSA-N [AlH3].[Mg] Chemical class [AlH3].[Mg] GANNOFFDYMSBSZ-UHFFFAOYSA-N 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
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical compound C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 description 1
- 229960002916 adapalene Drugs 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 235000014104 aloe vera supplement Nutrition 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000002431 aminoalkoxy group Chemical group 0.000 description 1
- 229940064734 aminobenzoate Drugs 0.000 description 1
- 229940059265 ammonium lactate Drugs 0.000 description 1
- 235000019286 ammonium lactate Nutrition 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229960000271 arbutin Drugs 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 125000004350 aryl cycloalkyl group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000003212 astringent agent Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 235000021302 avocado oil Nutrition 0.000 description 1
- 239000008163 avocado oil Substances 0.000 description 1
- RZOBLYBZQXQGFY-HSHFZTNMSA-N azanium;(2r)-2-hydroxypropanoate Chemical compound [NH4+].C[C@@H](O)C([O-])=O RZOBLYBZQXQGFY-HSHFZTNMSA-N 0.000 description 1
- 229960002255 azelaic acid Drugs 0.000 description 1
- XVAMCHGMPYWHNL-UHFFFAOYSA-N bemotrizinol Chemical compound OC1=CC(OCC(CC)CCCC)=CC=C1C1=NC(C=2C=CC(OC)=CC=2)=NC(C=2C(=CC(OCC(CC)CCCC)=CC=2)O)=N1 XVAMCHGMPYWHNL-UHFFFAOYSA-N 0.000 description 1
- 229960004101 bemotrizinol Drugs 0.000 description 1
- 229940054066 benzamide antipsychotics Drugs 0.000 description 1
- 150000003936 benzamides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- FQUNFJULCYSSOP-UHFFFAOYSA-N bisoctrizole Chemical compound N1=C2C=CC=CC2=NN1C1=CC(C(C)(C)CC(C)(C)C)=CC(CC=2C(=C(C=C(C=2)C(C)(C)CC(C)(C)C)N2N=C3C=CC=CC3=N2)O)=C1O FQUNFJULCYSSOP-UHFFFAOYSA-N 0.000 description 1
- AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 description 1
- DHAZIUXMHRHVMP-UHFFFAOYSA-N butyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCCCC DHAZIUXMHRHVMP-UHFFFAOYSA-N 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 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 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229940074979 cetyl palmitate Drugs 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000008406 cosmetic ingredient Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 125000001047 cyclobutenyl group Chemical class C1(=CCC1)* 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000035614 depigmentation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 229940028356 diethylene glycol monobutyl ether Drugs 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 1
- 229960000735 docosanol Drugs 0.000 description 1
- QQQMUBLXDAFBRH-UHFFFAOYSA-N dodecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCOC(=O)C(C)O QQQMUBLXDAFBRH-UHFFFAOYSA-N 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 229960002852 ellagic acid Drugs 0.000 description 1
- 235000004132 ellagic acid Nutrition 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- UVCJGUGAGLDPAA-UHFFFAOYSA-N ensulizole Chemical compound N1C2=CC(S(=O)(=O)O)=CC=C2N=C1C1=CC=CC=C1 UVCJGUGAGLDPAA-UHFFFAOYSA-N 0.000 description 1
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical class CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
- CBZHHQOZZQEZNJ-UHFFFAOYSA-N ethyl 4-[bis(2-hydroxypropyl)amino]benzoate Chemical compound CCOC(=O)C1=CC=C(N(CC(C)O)CC(C)O)C=C1 CBZHHQOZZQEZNJ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 235000008524 evening primrose extract Nutrition 0.000 description 1
- 239000010475 evening primrose oil Substances 0.000 description 1
- 229940089020 evening primrose oil Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 125000005640 glucopyranosyl group Chemical group 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- PXDJXZJSCPSGGI-UHFFFAOYSA-N hexadecanoic acid hexadecyl ester Natural products CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 1
- 229940100463 hexyl laurate Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003395 histamine H3 receptor antagonist Substances 0.000 description 1
- 238000006459 hydrosilylation reaction Methods 0.000 description 1
- 208000000069 hyperpigmentation Diseases 0.000 description 1
- 230000003810 hyperpigmentation Effects 0.000 description 1
- NITYDPDXAAFEIT-DYVFJYSZSA-N ilomastat Chemical compound C1=CC=C2C(C[C@@H](C(=O)NC)NC(=O)[C@H](CC(C)C)CC(=O)NO)=CNC2=C1 NITYDPDXAAFEIT-DYVFJYSZSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940078545 isocetyl stearate Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940093629 isopropyl isostearate Drugs 0.000 description 1
- 229940033357 isopropyl laurate Drugs 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940075495 isopropyl palmitate Drugs 0.000 description 1
- 229940089456 isopropyl stearate Drugs 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940074358 magnesium ascorbate Drugs 0.000 description 1
- AIOKQVJVNPDJKA-ZZMNMWMASA-L magnesium;(2r)-2-[(1s)-1,2-dihydroxyethyl]-4-hydroxy-5-oxo-2h-furan-3-olate Chemical compound [Mg+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] AIOKQVJVNPDJKA-ZZMNMWMASA-L 0.000 description 1
- GFTXWCQFWLOXAT-UHFFFAOYSA-M magnesium;cyclohexane;bromide Chemical compound [Mg+2].[Br-].C1CC[CH-]CC1 GFTXWCQFWLOXAT-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229940102398 methyl anthranilate Drugs 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
- 238000000386 microscopy Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229910052901 montmorillonite Inorganic materials 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- 229940078812 myristyl myristate Drugs 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000004957 nitroimidazoles Chemical class 0.000 description 1
- DLVYTANECMRFGX-UHFFFAOYSA-N norfuraneol Natural products CC1=C(O)C(=O)CO1 DLVYTANECMRFGX-UHFFFAOYSA-N 0.000 description 1
- 229940116918 octadecenedioic acid Drugs 0.000 description 1
- 229960000601 octocrylene Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- JCGNDDUYTRNOFT-UHFFFAOYSA-N oxolane-2,4-dione Chemical compound O=C1COC(=O)C1 JCGNDDUYTRNOFT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000003346 palm kernel oil Substances 0.000 description 1
- 235000019865 palm kernel oil Nutrition 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
- 239000000312 peanut oil Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 238000005887 phenylation reaction Methods 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
- 239000008363 phosphate buffer Substances 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- XEIOPEQGDSYOIH-MURFETPASA-N propan-2-yl (9z,12z)-octadeca-9,12-dienoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC(C)C XEIOPEQGDSYOIH-MURFETPASA-N 0.000 description 1
- NEOZOXKVMDBOSG-UHFFFAOYSA-N propan-2-yl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OC(C)C NEOZOXKVMDBOSG-UHFFFAOYSA-N 0.000 description 1
- ZPWFUIUNWDIYCJ-UHFFFAOYSA-N propan-2-yl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(C)C ZPWFUIUNWDIYCJ-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 231100000051 skin sensitiser Toxicity 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 235000020712 soy bean extract Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000020238 sunflower seed Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- BORJONZPSTVSFP-UHFFFAOYSA-N tetradecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCCCOC(=O)C(C)O BORJONZPSTVSFP-UHFFFAOYSA-N 0.000 description 1
- DZKXJUASMGQEMA-UHFFFAOYSA-N tetradecyl tetradecanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC DZKXJUASMGQEMA-UHFFFAOYSA-N 0.000 description 1
- PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 239000002750 tryptase inhibitor Substances 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 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
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/14—Nitrogen atoms not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/25—Silicon; Compounds thereof
-
- 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds thereof
-
- 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/29—Titanium; Compounds thereof
-
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
-
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
-
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
-
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4986—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with sulfur as the only hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/673—Vitamin B group
- A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- 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
-
- 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
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Emergency Medicine (AREA)
- Cosmetics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
公开了一种新型化合物。还公开了包含所述化合物的亮肤组合物和亮肤的方法。此外，公开了合成所述新型化合物的方法。
Description
技术领域
本发明涉及用于减少皮肤色素沉着过度的新型化合物。
背景技术
各种化妆品组合物被消费者广泛使用。使用护肤化妆品如乳剂和霜剂来获得益处，例如抗衰老、减少皮肤色素沉着过度和保湿。
皮肤作为生物最外层的保护性覆盖物，更容易受到暴露于诸如阳光、热量、湿气、污染和灰尘等因素的影响。过度暴露于这些因素可能导致例如晒黑、皮肤有斑点、色素沉着过度、雀斑、黄褐斑等情况，这可能进一步导致例如不太合意的不均匀的肤色。
减少此类情况的一种可能方法是确保最大限度地减少暴露于上述影响因素，特别是阳光。一般认为，过度暴露于阳光并因此暴露于其中所含的有害紫外线会产生晒黑效果。然而，仅确保最低限度地暴露于此类因素并不总是足够的，并且在大多数情况下，暴露于特别是阳光的这些因素是不可避免的。
正是由于这些原因，人们一直依靠使用化妆品来减少皮肤的色素沉着过度和/或甚至使肤色均匀。亮肤剂在本领域中是众所周知的。然而，许多已知的物质如曲酸往往具有低功效或可能导致不良副作用，诸如皮肤刺激。因此，替代的亮肤剂例如可以提供更好的皮肤色素沉着过度减少和/或无副作用或低副作用是非常需要的。
WO 99/04752(Johnson and Johnson)公开了一种用于提供改变哺乳动物皮肤色素沉着的方法和组合物，包括局部施用通过PAR-2途径起作用的化合物。特别地，它公开了作用为增加色素沉着的胰蛋白酶、类胰蛋白酶、丝氨酸蛋白酶或作用为PAR-2激动剂的化合物。并且，还公开了胰蛋白酶抑制剂、凝血酶抑制剂、类胰蛋白酶抑制剂作为PAR-2途径抑制剂或作为PAR-2拮抗剂而用于脱色素。
WO 98/56757和JP2000178188(均为Sankyo Co的)通过其中给出的通式公开了苄胺衍生物。已显示该化合物及其药学上可接受的盐具有优异的回肠胆汁酸转运体抑制活性。
现已发现一类新的根据式1的化合物或其化妆品上可接受的盐。已发现这些化合物提供皮肤色素沉着过度减少的效果。此外，已发现这些化合物在减少皮肤色素沉着过度和/或无副作用或低副作用如皮肤刺激方面提供了良好的功效。
发明内容
在第一方面，本发明提供如权利要求1所述的新型化合物或其化妆品上可接受的盐。
在第二方面，本发明提供一种减少老年斑和雀斑的美容方法，包括施用根据本发明的组合物的步骤，该组合物包含式1的化合物或其化妆品上可接受的盐。
定义
如本文所用，“盐”是指卤素盐、甲苯磺酸盐、甲磺酸盐、硫酸盐、磷酸盐、柠檬酸盐、酒石酸盐、直链、支链或环状羧酸盐和二羧酸盐；特别是C2至C12烷基羧酸盐；它可以是饱和或不饱和的，并可以被选自氧的杂原子以及化妆品工业中使用的任何其他抗衡离子取代。
除非另有说明，否则本文所用的量以基于组合物总重量的重量百分比表示，并缩写为“重量％”。
如本文所用，“增亮”意指减少皮肤的色素沉着过度，如老年斑和雀斑。
发明详述
本发明提供根据式1的化合物或其化妆品上可接受的盐，
其中，
R1是对异丙氧基，R2是环己基，R3是氢，X是氧，n＝1且m＝1；
R1是对异丙氧基，R2是环己基，R3是甲基，X是氧，n＝1且m＝1；
R1是对异丙氧基，R2是环戊基，R3是氢，X是氧，n＝1且m＝1；
R1是对异丙氧基，R2是乙基，R3是氢，X是氧，n＝1且m＝1；
R1是对异丙氧基，R2是甲基，R3是氢，X是氧，n＝1且m＝1；
R1是对甲氧基，R2是环戊基，R3是氢，X是氧，n＝1且m＝1；
R1是对甲基，R2是环戊基，R3是氢，X是氧，n＝1且m＝1；
R1是对异丙氧基，R2是异丙基，R3是氢，X是氧，n＝1且m＝1；
R1是对异丙氧基，R2是环己基，R3是氢，X是氧，n＝1且m＝0；
R1是对叔丁氧基甲基，R2是环戊基，R3是氢，X是氧，n＝1且m＝1；
R1是对乙基，R2是环戊基，R3是氢，X是氧，n＝1且m＝1；
R1是对异丁基，R2是环戊基，R3是氢，X是氧，n＝1且m＝1；
R1是间异丙氧基，R2是环己基，R3是氢，X是氧，n＝1且m＝1。
式1的化合物的优选实例是：
N-(环己基(4-异丙氧基苯基)甲基)四氢-2H-吡喃-4-胺
已发现根据本发明的化合物提供减少皮肤色素沉着过度的作用。
根据本发明的组合物
本发明进一步涉及一种组合物，其包含本发明的化合物即式1的化合物，或其化妆品上可接受的盐，以及化妆品上可接受的基质。
根据本发明的组合物可以是用于局部施用于哺乳动物，尤其是人类皮肤的组合物。这种组合物通常可分类为免洗型或洗去型，并且意在包括调理剂或醒肤剂(tonic)、口红、彩妆品和一般局部组合物。
根据本发明的组合物优选为免洗型组合物。
根据本发明的组合物包含0.001至20重量％，优选0.01至15重量％，更优选0.1至10重量％，甚至更优选0.5至5重量％，最优选1至3重量％的式1的化合物或其化妆品上可接受的盐。
化妆品上可接受的基质
所述组合物包含化妆品上可接受的基质，以充当组合物中存在的其他材料的稀释剂、分散剂或载体，以在组合物施用于皮肤时促进其分布。
化妆品上可接受的基质包括具有10至30个碳原子的脂肪酸及其盐、水、液体或固体润肤剂、溶剂、湿润剂、增稠剂和粉末、皮肤渗透增强剂，并且可以单独使用或以它们的混合物的形式使用。
具有10至30个碳原子的脂肪酸的说明性实例包括壬酸、月桂酸、肉豆蔻酸、棕榈酸、硬脂酸、异硬脂酸、油酸、亚油酸、花生酸、山萮酸或芥酸及其混合物。脂肪酸的盐的说明性实例是硬脂酸钾。
润肤剂的说明性实例包括硬脂醇、甘油单蓖麻油酸酯、貂油、鲸蜡醇、异硬脂酸异丙酯、硬脂酸、棕榈酸异丁酯、硬脂酸异鲸蜡酯、油醇、月桂酸异丙酯、月桂酸己酯、油酸癸酯、十八-2-醇、异鲸蜡醇、二十烷醇、山萮醇、棕榈酸鲸蜡酯、诸如二甲基聚硅氧烷之类的硅油、癸二酸二正丁酯、肉豆蔻酸异丙酯、棕榈酸异丙酯、硬脂酸异丙酯、硬脂酸丁酯、聚乙二醇、三甘醇、羊毛脂、可可脂、玉米油、棉籽油、橄榄油、棕榈仁油、菜籽油、红花籽油、月见草油、大豆油、葵花籽油、鳄梨油、芝麻籽油、椰子油、花生油、蓖麻油、乙酰化羊毛脂醇、矿脂、矿物油、肉豆蔻酸丁酯、异硬脂酸、棕榈酸、亚油酸异丙酯、乳酸月桂酯、乳酸肉豆蔻酯、油酸癸酯和肉豆蔻酸肉豆蔻酯。
溶剂的说明性实例包括乙醇、异丙醇、丙酮、乙二醇单乙醚、二甘醇单丁醚和二甘醇单乙醚。
粉末的说明性实例包括白垩、滑石、漂白土、高岭土、淀粉、树胶、胶体二氧化硅、聚丙烯酸钠、四烷基和/或三烷基芳基铵蒙脱石、化学改性的硅酸铝镁、有机改性蒙脱土粘土、水合硅酸铝、热解法二氧化硅、羧乙烯基聚合物、羧甲基纤维素钠和乙二醇单硬脂酸酯。
被认为增强皮肤渗透的化合物，如二甲亚砜也可用作化妆品上可接受的基质。
优选的基质是水、硬脂酸、硬脂酸钾及其混合物。
化妆品上可接受的基质通常以10至99.9重量％，优选50-99重量％存在，并且可以形成组合物的余量。
包含根据本发明的化合物的组合物还可包含另外的亮肤剂。
另外的亮肤剂
另外的亮肤剂的说明性实例包括维生素B3化合物、维生素B6、维生素C、维生素A、间苯二酚衍生物、12-羟基硬脂酸、谷胱甘肽前体、加拉定(galardin)、阿达帕林、芦荟提取物、乳酸铵、熊果苷、壬二酸、丁羟基茴香醚、丁羟基甲苯、柠檬酸酯、脱氧熊果苷、1,3-二苯丙烷衍生物、2,5-二羟基苯甲酸及其衍生物、2-(4-乙酰氧苯基)-1,3-二噻烷、2-(4-羟苯基)-1,3-二噻烷、鞣花酸、葡糖呲喃糖基-1-抗坏血酸酯、葡糖酸、乙醇酸、绿茶提取物、4-羟基-5-甲基-3[2H]-呋喃酮、氢醌、4-羟基茴香醚及其衍生物、4-羟基苯甲酸衍生物、羟基辛酸、肌醇抗坏血酸酯、曲酸、乳酸、柠檬提取物、亚油酸、抗坏血酸磷酸酯镁、5-辛酰基水杨酸、水杨酸、3,4,5-三羟基苄基衍生物、十八碳烯二酸、乙酰氨基葡萄糖、Pitera提取物、馨肤白(symwhite)、泛酸钙(Melano-block)、Seppiwhite、大豆提取物(bowman birk抑制剂)以及其混合物。
优选的亮肤剂是维生素B3化合物，即烟酸、烟酰胺、烟醇或其衍生物或盐、维生素B6、间苯二酚衍生物(即2,4-取代间苯二酚衍生物、3,5-取代间苯二酚衍生物、己基间苯二酚和苯乙基间苯二酚)、12-羟基硬脂酸、谷胱甘肽前体和加拉定。
当掺入组合物中时，优选添加0.001-15重量％，更优选0.01-10重量％，最优选0.1-5重量％的另外的亮肤剂。
根据本发明的组合物可以包括式1的化合物与至少一种选自烟酰胺、12-羟基硬脂酸、谷胱甘肽前体、间苯二酚衍生物(特别是己基间苯二酚)、十八碳烯二酸、乙酰氨基葡萄糖、Pitera提取物、馨肤白、泛酸钙(Melano-block)、Seppiwhite和大豆提取物(bowmanbirk抑制剂)的化合物的组合。
防晒剂
有机防晒剂
所述组合物优选另外包含一种或多种有机防晒剂。多种有机防晒剂适合用于本发明的组合物中。
合适的UV-A/UV-B防晒剂包括：2-羟基-4-甲氧基二苯甲酮、辛基二甲基对氨基苯甲酸、二没食子酰基三油酸酯、2,2-二羟基-4-甲氧基二苯甲酮、乙基-4-(双(羟丙基))氨基苯甲酸酯、2-乙基己基-2-氰基-3,3-二苯基丙烯酸酯、2-乙基己基水杨酸酯、对氨基苯甲酸甘油酯、3,3,5-三甲基环己基水杨酸酯、邻氨基苯甲酸甲酯、对二甲基氨基苯甲酸或氨基苯甲酸酯、2-乙基己基-对二甲基氨基苯甲酸酯、2-苯基苯并咪唑-5-磺酸、2-(对二甲基氨基苯基)-苯并噁唑-5-磺酸、2-乙基己基-对甲氧基肉桂酸酯、二苯甲酰甲烷衍生物、2-羟基-4-甲氧基二苯甲酮、辛基二甲基-对氨基苯甲酸、二乙基己基萘甲酸酯、Mexoryl、TinosorbS、Tinosorb M及其混合物。
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、2-甲基二苯甲酰甲烷、4-甲基-二苯甲酰乙烷、4-异丙基二苯甲酰甲烷、4-叔丁基二苯甲酰甲烷、2,4-二甲基二苯甲酰甲烷、2,5-二甲基二苯甲酰甲烷、4,4'-二异丙基二苯甲酰甲烷、2-甲基-5-异丙基-4'-甲氧基二苯甲酰甲烷、2-甲基-5-叔丁基-4'-甲氧基二苯甲酰甲烷、2,4-二甲基-4'-甲氧基二苯甲酰甲烷或2,6-二甲基-4-叔丁基-4'-甲氧基二苯甲酰甲烷。
优选的有机防晒剂是2-乙基己基-对甲氧基肉桂酸酯(Parsol MCX)、二苯甲酰甲烷衍生物；特别是4-叔丁基-4'-甲氧基二苯甲酰甲烷(Parsol 1789)、2-乙基己基-2-氰基-3,3-二苯基-2-丙烯酸酯(Octocrylene)或其混合物。
在本发明的组合物中可以使用有效量的有机防晒剂。该组合物优选包含0.1至15重量％，更优选1至10重量％，最优选2至5重量％的有机防晒剂。
无机防晒剂
该组合物可进一步包含无机防晒剂。无机防晒剂的说明性实例是氧化锌、氧化铁、二氧化硅如热解法二氧化硅、或二氧化钛。
优选的无机防晒剂是二氧化钛(TiO2)和氧化锌(ZnO)。
该组合物优选包含0.1至15重量％，更优选1至10重量％，最优选2至5重量％的无机防晒剂。
亮肤的方法
本发明还涉及一种使人的皮肤增亮的方法。该方法包括将包含根据本发明的化合物的组合物施用到人皮肤上的步骤。
任选的化妆品成分
本发明的组合物可以包含范围广泛的其他任选组分。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、芳香剂、湿润剂、遮光剂、调理剂、去角质剂、pH调节剂、防腐剂、天然提取物、精油、皮肤敏化剂、皮肤舒缓剂，以及皮肤修复剂。
产品形式
根据本发明的组合物优选配制成粉末、薄片、乳剂、霜剂、凝胶或摩丝的形式。
根据本发明的化合物的合成
式1的本发明化合物可归类为苄胺衍生物。已经使用本领域技术人员已知的标准合成转化和方法，例如通过酮衍生物的还原胺化或烷基(芳基)卤代甲烷的胺化，合成了具有本发明的式1化合物的基本特征的苄胺衍生物的许多实例。以下现有技术详细描述了本领域技术人员可获得的标准合成转化和方法，以使得能够制备本发明的式1化合物：N.Toda等(2003)：“Design,synthesis and structure-activity relationships of dualinhibitors of acetylcholinesterase and serotonin transporter as potentialagents for Alzheimer’s disease”，Bioorganic and Medicinal Chemistry,11,1935-1955(化合物13、14a-g、27和28)；D.L.J.Clive等(2003)：“Derivatized amino acidsrelevant to native peptide synthesis by chemical ligation and acyl transfer”，Journal of Organic Chemistry,68,9247-9254(描述的几个实施例)；R.Sheng等(2005)：“Design,synthesis and evaluation of 2-phenoxy-indan-1-one derivatives asacetylcholinesterase inhibitors”，Bioorganic and Medicinal Chemistry,15,2834-2837(化合物4a、b和5a-l)；J.Cherian(2011)：“Structure-activity relationships ofantitubercular nitroimidazoles.3.Exploration of the linker and lipophilictail of((S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl)-(4-trifluoromethoxybenzyl)amine(6-Amino PA-824)”，Journal of Medicinal Chemistry,54,5639-5659(化合物14a-c、15a-c和17a-i)；O.Rahman等(2004)：“Synthesis of[11C]/(113C)amines via carbonylation followed by reductive amination”，Organic andBiomolecular Chemistry,2,1612-1616(化合物21a-k)；A.R.Hajipour等(2001)：“Butyltriphenyl-phosphonium tetraborate(BTPPTB)as a selective reducing agentfor the reduction of imines,enamines and oximes and reductive alkylation ofaldehydes or ketones with primary amines in methanol or under solid-phaseconditions"，Indian Journal of Chemistry,Section B:Organometallic ChemistryIncluding Medicinal Chemistry,40B,152-156；C.Salmi等(2006)：“Efficientdiastereoselective titanium(IV)reductive amination of ketones”，Letters inOrganic Chemistry,3,384-389；K.Hitoshi等(2001)：“Preparation of cyclobutenederivatives as bile acid transporter inhibitors”，EP 1070703 A1(描述的几个实施例)；F.Gasparrini等(1988)：“Nitric acid facile oxidation of mono-anddiarylcarbinols to carbonyl compounds in a biphasic system”，SyntheticCommunications,18,69-75；Chao-Jun Li and Yue Meng(2000)：“Grignard-typecarbonyl phenylation in water and under an air atmosphere”，Journal of theAmerica Chemical Society,122,9538-9539(条目9和10)；Alois Fuerstner and HelgaKrause(2001)：“Practical method for the rhodium-catalyzed addition of aryl-andalkenylboronic acids to aldehydes”，Advanced Synthesis&Catalysis,343,343-350(条目3、4、5、14、15和16)；H.Pajouhesh等(2010)：“Structure-activity relationshipsof diphenylpiperazine N-type calcium channel inhibitors”，Bioorganic andMedicinal Chemistry Letters,20,1378-1383；J.Belzner等(1989)：“Synthesis of[1.1.1.]propellanes”，Chemische Berichte,122,1509-1529；T.Kolasa等(2000)：“Heteroarylmethoxyphenyl-alkoxyiminoalkylcarboxylic acids as leukotrienebiosynthesis inhibitors”，Journal of Medicinal Chemistry,43,690-705(化合物86、101、104和138)；G.W.Kalbalka等(2001)：“Alkylation of aromatic aldehydes withalkylboron chloride derivatives”，Tetrahedron,57,1663-1670(描述的几个实施例)；C.Keh等(2003)：“The Barbier-Grignard-type carbonyl alkylation usingunactivated alkyl halides in water”，Journal of the American Chemical Society,125,4062-4063(描述的几个实施例)；R.Apodaca等(2003)：“A new class of diamine-based human histamine H3 receptor antagonists:4-(aminoalkoxy)benzylamines”，Journal of Medicinal Chemistry,46,3938-3944(化合物14)；S-B Qi等(2013)：“Copper-dipyridylphosphine-catalyzed hydrosilylation:enantioselective synthesis ofaryl-and heteroarylcycloalkyl alcohols”，Organic and Biomolecular Chemistry,11,929-937；Davood Setamdideh and Behzad Zeynizadeh(2006)：“Mild and convenientmethod for reduction of carbonyl compounds with the NaBH4/charcoal system inwet THF”，Zeitschrift fuer Naturforschung B:Chemical Sciences,61,1275-1281(描述的几个实施例)。
实施例中的缩写
ACN＝乙腈
d＝天
DCM＝二氯甲烷
DMF＝N,N-二甲基甲酰胺
DMSO＝二甲亚砜
EA＝乙酸乙酯
EtOH＝乙醇
FC＝快速色谱
g＝克
HPLC-UV＝带紫外检测的高效液相色谱
1H-NMR＝质子核磁共振
K2CO3＝碳酸钾
LC-MS＝液相色谱-质谱联用检测
MHz＝兆赫
ul＝微升
ml＝毫升
mmol＝毫摩尔
Na2SO4＝硫酸钠
PBS＝磷酸盐缓冲液
PMA＝磷钼酸
R.T.＝室温
TEA＝三乙胺
TFA＝三氟乙酸
THF＝四氢呋喃
TLC＝薄层色谱
以下使用非限制性实施例进一步描述本发明。
具体实施方式
实施例1
N-(环己基(4-异丙氧基苯基)甲基)四氢-2H-吡喃-4-胺
将2-溴丙烷(30.2g,246mmol)添加到4-羟基苯甲醛(20g，164mmol)和碳酸钾(K2CO3)(45.3g，328mmol)在N,N-二甲基甲酰胺(DMF)(150ml)中的混合物中，并在50℃下搅拌混合物，直到如薄层色谱法(TLC)所监测的4-羟基苯甲醛完全消失。将混合物在乙酸乙酯(EA)(300ml)和水(300ml)之间分配，有机层用硫酸钠(Na2SO4)干燥，过滤并在真空中除去溶剂，得到粗4-异丙氧基苯甲醛(26g，96％)。将4-异丙氧基苯甲醛(10g，61mmol)在四氢呋喃(THF)(60ml)中的溶液添加到环己基溴化镁(12.6g，67.1mmol-由环己基溴和镁制备)在THF(60ml)中的溶液中，并在室温(RT)下搅拌溶液，直到如通过TLC监测的4-异丙氧基苯甲醛的消耗。将混合物在EA(200ml)和水(200ml)之间分配，有机层用Na2SO4干燥，过滤并在真空中除去溶剂，得到环己基(4-异丙氧基苯基)甲醇，将其通过快速色谱法纯化，得到无色油形式的纯产物(6g，40％)。将甲磺酰氯(3.1ml，40mmol)加入到环己基(4-异丙氧基苯基)甲醇(6g，36.5mmol)在二氯甲烷(DCM)(60ml)中的溶液中，随后加入三乙胺(TEA)(5.9ml，42mmol)，并在室温下搅拌溶液，直到如通过TLC监测的环己基(4-异丙氧基苯基)甲醇的消耗。将混合物在EA(200ml)和水(200ml)之间分配，有机层用Na2SO4干燥，过滤并在真空中除去溶剂，得到粗1-(氯(环己基)甲基)-4-异丙氧基苯(6g，92％)，将其不经进一步纯化就用于下一步骤。将四氢-2H-吡喃-4-胺(114ul，1.1mmol)加入到1-(氯(环己基)甲基)-4-异丙氧基苯(300mg，1.1mmol)在乙腈(ACN 2ml)中的溶液中，并在室温下搅拌溶液，直到如通过TLC监测的1-(氯(环己基)甲基)-4-异丙氧基苯的消耗。将混合物在EA(200ml)和水(200ml)之间分配，有机层用Na2SO4干燥，过滤并在真空中除去溶剂，得到粗N-(环己基(4-异丙氧基苯基)甲基)四氢-2H-吡喃-4-胺(120mg，32％)，将其通过快速色谱法纯化，得到在静置后固化的无色油形式的纯产物。HPLC-UV显示>99％的纯度。LC-MS(ESI+)显示出期望的质量[M+H]+332.5；1H NMR(400MHz)δ7.34(2H,dd),7.02(2H,dd),4.51(1H,m),3.81(2H,m),3.10(2H,m),2.70(1H,m),1.90-1.28(10H,m),1.23(6H,d),1.08-0.76(7H,m)。
黑色素模型(MelanoDerm)测试
对照化合物由阴性对照物(超纯水)、载体对照物(超纯水中的DMSO-最终浓度为0.1％)和阳性对照物(超纯水中的2％曲酸-最终浓度为700uM)组成。测试化合物在DMSO中以10mM的浓度制备，并用EPI-100-LLMM培养基(Mattek Corp.)稀释至10uM的最终浓度。在用测试化合物和对照物处理之前，将黑色素模型人体组织(MEL-300-B，Matek Corp.)用EPI-100-NMM培养基平衡24小时，随后用EPI-100-LLMM培养基平衡48小时。按照标准方案，用对照物和测试化合物对黑色素模型进行给药(dosing)和再供料(re-feeding)总共12天，收集黑色素模型用于黑色素定量、活力分析和宏观/微观成像分析。对于黑色素定量，将组织悬浮在PBS缓冲液(5ml)中5分钟，从PBS中取出并用额外的PBS(2ml)洗涤/漂洗。用1％的碳酸氢钠溶液(300ul)处理组织30分钟，随后去除碳酸氢钠溶液并用PBS溶液(2X 2ml)洗涤/漂洗。将组织悬浮在Solvable试剂(500ul)中，并在95℃下与黑色素标准样品(通过将黑色素(cat#M8631，Sigma-Aldrich)悬浮在Solvable试剂中以生成0、2.5、5、10、25、50和100ug的黑色素标准物而制备)一起温育24小时。将所有温育样品以13000rpm离心5分钟，并在490nm读取/测定上清液的光密度。从黑色素标准样品校准曲线确定来自每个组织样品的黑色素量(ug)。使用BCA蛋白质测定试剂盒(Pierce)测定组织样品的蛋白质浓度，将黑色素含量标准化，并表示为黑色素(ug)/蛋白质(ug)(表1)。使用WST-1试剂盒(cat#05015944001，Roche)测定相对于阴性对照物和载体对照物的作为测试化合物给药/供料的结果的组织活力。对组织图像进行宏观(macroscopically)检查以评估测试化合物与阴性、载体和阳性对照相比的亮肤能力，并通过显微镜(10X放大)评估细胞毒性。
Melanoderm数据
表1用实施例1的化合物处理后melanoderm中黑色素含量的降低
a来自n＝3个样品的平均值+/-标准偏差。
b与载体对照物相比的T检验。
cP<0.001时表示统计学显著。
dP<0.02时表示统计学显著。
实施例1的化合物显示出降低的黑色素含量，清楚地显示出亮肤效果。
Claims (7)
1.式1的化合物或其化妆品上可接受的盐，
其中，
R1是对异丙氧基，R2是环己基，R3是氢，X是氧，n＝1且m＝1；
R1是对异丙氧基，R2是环己基，R3是甲基，X是氧，n＝1且m＝1；
R1是间异丙氧基，R2是环己基，R3是氢，X是氧，n＝1且m＝1。
2.一种组合物，其包含
·0.001-20重量％的根据权利要求1所述的化合物，和
·化妆品上可接受的基质。
3.根据权利要求2所述的组合物，其包含0.001-15重量％的至少一种选自烟酰胺、12-羟基硬脂酸、间苯二酚衍生物的另外的亮肤剂。
4.根据权利要求2或3所述的组合物，其包含0.1-15重量％的至少一种有机防晒剂。
5.根据权利要求2至4中任一项所述的组合物，其包含0.1-15重量％的至少一种无机防晒剂。
6.一种淡化老年斑和雀斑的非治疗性美容方法，包括将根据权利要求2至5中任一项所述的组合物施用于皮肤。
7.根据权利要求1所述的化合物在制备用于淡化老年斑和雀斑的试剂中的用途。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP19193957.8 | 2019-08-28 | ||
| EP19193957 | 2019-08-28 | ||
| PCT/EP2020/073561 WO2021037759A1 (en) | 2019-08-28 | 2020-08-21 | Novel compounds for skin lightening |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114375291A CN114375291A (zh) | 2022-04-19 |
| CN114375291B true CN114375291B (zh) | 2024-03-08 |
Family
ID=67777117
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080061076.9A Active CN114375291B (zh) | 2019-08-28 | 2020-08-21 | 用于亮肤的新型化合物 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20220280405A1 (zh) |
| EP (1) | EP4021899A1 (zh) |
| CN (1) | CN114375291B (zh) |
| MX (1) | MX2022002300A (zh) |
| WO (1) | WO2021037759A1 (zh) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5858997A (en) * | 1997-12-04 | 1999-01-12 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Method and composition for skin lightening |
| CN102686212A (zh) * | 2009-11-09 | 2012-09-19 | 荷兰联合利华有限公司 | 包含苯氧基烷基胺的护肤组合物 |
| CN108368026A (zh) * | 2015-12-16 | 2018-08-03 | 莱雅公司 | 针对其化妆用途的间苯二酚衍生物 |
| CN109661224A (zh) * | 2016-09-06 | 2019-04-19 | 荷兰联合利华有限公司 | 用于降低细胞黑色素含量的化合物 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998056757A1 (fr) | 1997-06-11 | 1998-12-17 | Sankyo Company, Limited | Derives de benzylamine |
| US8039026B1 (en) | 1997-07-28 | 2011-10-18 | Johnson & Johnson Consumer Companies, Inc | Methods for treating skin pigmentation |
| JP2000178188A (ja) | 1998-12-11 | 2000-06-27 | Sankyo Co Ltd | 回腸型胆汁酸トランスポ−タ−阻害剤 |
| CZ290178B6 (cs) | 1999-07-22 | 2002-06-12 | Sankyo Company Limited | Deriváty cyklobutenu |
| EP2409976A4 (en) * | 2009-03-19 | 2012-09-19 | Taisho Pharmaceutical Co Ltd | GLYCINTRANSPORTERHEMMER |
| US8425885B2 (en) * | 2009-11-09 | 2013-04-23 | Conopco, Inc. | Substituted 3-(phenoxymethyl) benzyl amines and personal care compositions |
| US8293218B2 (en) * | 2010-07-29 | 2012-10-23 | Conopco, Inc. | Skin care compositions comprising substituted monoamines |
| FR3030250B1 (fr) * | 2014-12-22 | 2018-11-02 | L'oreal | Composition aqueuse comprenant un compose 4-(heterocycloalkyl)-benzene-1,3-diol et un hydrotrope |
-
2020
- 2020-08-21 WO PCT/EP2020/073561 patent/WO2021037759A1/en unknown
- 2020-08-21 MX MX2022002300A patent/MX2022002300A/es unknown
- 2020-08-21 EP EP20767479.7A patent/EP4021899A1/en active Pending
- 2020-08-21 CN CN202080061076.9A patent/CN114375291B/zh active Active
- 2020-08-21 US US17/633,229 patent/US20220280405A1/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5858997A (en) * | 1997-12-04 | 1999-01-12 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Method and composition for skin lightening |
| CN102686212A (zh) * | 2009-11-09 | 2012-09-19 | 荷兰联合利华有限公司 | 包含苯氧基烷基胺的护肤组合物 |
| CN108368026A (zh) * | 2015-12-16 | 2018-08-03 | 莱雅公司 | 针对其化妆用途的间苯二酚衍生物 |
| CN109661224A (zh) * | 2016-09-06 | 2019-04-19 | 荷兰联合利华有限公司 | 用于降低细胞黑色素含量的化合物 |
Non-Patent Citations (1)
| Title |
|---|
| STN Registry database.2009, * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114375291A (zh) | 2022-04-19 |
| EP4021899A1 (en) | 2022-07-06 |
| WO2021037759A1 (en) | 2021-03-04 |
| US20220280405A1 (en) | 2022-09-08 |
| MX2022002300A (es) | 2022-03-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101039220B1 (ko) | 미백제 및 피부 외용제 | |
| EP2516399B1 (fr) | Derives phenoliques, et leur utilisation pharmaceutique ou cosmetique | |
| JP5823696B2 (ja) | メラニン産生抑制剤 | |
| CN105050664B (zh) | 由烷基酰胺基噻唑和紫外滤光物质组成的组合 | |
| CN105050575A (zh) | 烷基酰胺基噻唑以及防腐剂的组合 | |
| UA57106C2 (uk) | Фармацевтична композиція місцевого призначення для відбілювання або зменшення пігментації шкіри у людини, спосіб відбілювання або зменшення пігментації шкіри у людини, фармацевтична композиція місцевого або трансдермального призначення для лікування запального захворювання шкіри у людини та спосіб лікування запального захворювання шкіри у людини | |
| KR20050058446A (ko) | 쿠마린 유도된 레조르시놀 유도체를 포함하는 피부 미백제 | |
| EP2514402B1 (en) | Preventing or ameliorating agent for pigmentation | |
| WO2011130400A1 (en) | Methods for providing enhanced resveratrol activity using 4-acetoxy-resveratrol | |
| JPH11255639A (ja) | チロシナーゼ活性阻害剤及び化粧料 | |
| JP2011519376A (ja) | メラニン形成修飾剤としてのステロイド化合物およびその使用 | |
| EP3664775B1 (en) | A personal care composition | |
| CN114375291B (zh) | 用于亮肤的新型化合物 | |
| JP2011241164A (ja) | 組成物 | |
| JPWO2014092166A1 (ja) | チロシナーゼ活性阻害剤及び美白剤 | |
| JPH1072330A (ja) | チロシナーゼ活性阻害剤及び化粧料 | |
| EP3509566B1 (en) | Compounds for reducing cellular melanin content | |
| EP4021391B1 (en) | Novel compounds for skin lightening | |
| JP5236335B2 (ja) | ラノスタ−８−エン誘導体およびこれらを含有する皮膚外用剤 | |
| JPH0848621A (ja) | 美白化粧料 | |
| JP4249958B2 (ja) | 特定のジフェニル酢酸エステル及びこれらを含有する皮膚外用剤 | |
| JPH10194919A (ja) | 皮膚外用剤 | |
| WO2015159384A1 (ja) | 新規な化合物、これを含有する化粧料及び皮膚外用剤 | |
| JPH06128203A (ja) | 皮膚外用剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |