EP4329718A1 - Compositions topiques comprenant des (glyco)sphingolipides et/ou des (glyco)céramides - Google Patents
Compositions topiques comprenant des (glyco)sphingolipides et/ou des (glyco)céramidesInfo
- Publication number
- EP4329718A1 EP4329718A1 EP22726199.7A EP22726199A EP4329718A1 EP 4329718 A1 EP4329718 A1 EP 4329718A1 EP 22726199 A EP22726199 A EP 22726199A EP 4329718 A1 EP4329718 A1 EP 4329718A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- skin
- ceramide
- individual
- carbon
- formula
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 217
- 230000000699 topical effect Effects 0.000 title claims abstract description 131
- 229940106189 ceramide Drugs 0.000 title claims description 102
- 150000001783 ceramides Chemical class 0.000 title description 26
- 150000003408 sphingolipids Chemical class 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 131
- -1 lactosyl moiety Chemical group 0.000 claims abstract description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
- 239000001257 hydrogen Substances 0.000 claims abstract description 33
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 31
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims abstract description 29
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 13
- 125000002252 acyl group Chemical group 0.000 claims abstract description 12
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000003147 glycosyl group Chemical group 0.000 claims abstract description 8
- 210000003491 skin Anatomy 0.000 claims description 202
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 claims description 75
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 claims description 75
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 claims description 75
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 claims description 75
- 238000000034 method Methods 0.000 claims description 48
- 230000008591 skin barrier function Effects 0.000 claims description 47
- 210000002615 epidermis Anatomy 0.000 claims description 46
- 210000002510 keratinocyte Anatomy 0.000 claims description 40
- 230000015572 biosynthetic process Effects 0.000 claims description 38
- 230000001965 increasing effect Effects 0.000 claims description 38
- 239000002537 cosmetic Substances 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 33
- 238000003786 synthesis reaction Methods 0.000 claims description 30
- 102000004190 Enzymes Human genes 0.000 claims description 23
- 108090000790 Enzymes Proteins 0.000 claims description 23
- WPIHMWBQRSAMDE-YCZTVTEBSA-N beta-D-galactosyl-(1->4)-beta-D-galactosyl-N-(pentacosanoyl)sphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO[C@@H]1O[C@H](CO)[C@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O)[C@H](O)\C=C\CCCCCCCCCCCCC WPIHMWBQRSAMDE-YCZTVTEBSA-N 0.000 claims description 23
- 230000011712 cell development Effects 0.000 claims description 21
- ATGQXSBKTQANOH-UWVGARPKSA-N N-oleoylphytosphingosine Chemical compound CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@H](CO)NC(=O)CCCCCCC\C=C/CCCCCCCC ATGQXSBKTQANOH-UWVGARPKSA-N 0.000 claims description 20
- 150000002305 glucosylceramides Chemical class 0.000 claims description 20
- 208000017520 skin disease Diseases 0.000 claims description 20
- KZTJQXAANJHSCE-OIDHKYIRSA-N N-octodecanoylsphinganine Chemical compound CCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)CCCCCCCCCCCCCCC KZTJQXAANJHSCE-OIDHKYIRSA-N 0.000 claims description 19
- 241000282414 Homo sapiens Species 0.000 claims description 18
- 230000001771 impaired effect Effects 0.000 claims description 17
- 210000000434 stratum corneum Anatomy 0.000 claims description 16
- 230000032683 aging Effects 0.000 claims description 12
- 230000037303 wrinkles Effects 0.000 claims description 11
- 230000001575 pathological effect Effects 0.000 claims description 10
- 206010013786 Dry skin Diseases 0.000 claims description 9
- 239000003344 environmental pollutant Substances 0.000 claims description 9
- 230000000144 pharmacologic effect Effects 0.000 claims description 9
- 231100000719 pollutant Toxicity 0.000 claims description 9
- 239000012049 topical pharmaceutical composition Substances 0.000 claims description 9
- 201000008937 atopic dermatitis Diseases 0.000 claims description 8
- 230000037336 dry skin Effects 0.000 claims description 8
- 206010021198 ichthyosis Diseases 0.000 claims description 8
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 7
- 239000000839 emulsion Substances 0.000 claims description 7
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 claims description 7
- 231100001261 hazardous Toxicity 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 230000036572 transepidermal water loss Effects 0.000 claims description 7
- 230000009286 beneficial effect Effects 0.000 claims description 6
- 238000009499 grossing Methods 0.000 claims description 6
- 230000000116 mitigating effect Effects 0.000 claims description 6
- 230000002028 premature Effects 0.000 claims description 6
- 230000008093 supporting effect Effects 0.000 claims description 6
- 230000000007 visual effect Effects 0.000 claims description 6
- 201000004624 Dermatitis Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 208000010668 atopic eczema Diseases 0.000 claims description 5
- 230000007613 environmental effect Effects 0.000 claims description 5
- 239000000779 smoke Substances 0.000 claims description 5
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 4
- 206010048218 Xeroderma Diseases 0.000 claims description 4
- 206010000496 acne Diseases 0.000 claims description 4
- 235000019504 cigarettes Nutrition 0.000 claims description 4
- 125000000403 lignoceroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 239000013618 particulate matter Substances 0.000 claims description 4
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001124 arachidoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000006210 lotion Substances 0.000 claims description 3
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 210000004761 scalp Anatomy 0.000 claims description 2
- 239000002453 shampoo Substances 0.000 claims description 2
- 230000003827 upregulation Effects 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 20
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 20
- 150000002632 lipids Chemical class 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 14
- 102100024279 Phosphomevalonate kinase Human genes 0.000 description 13
- 108091000116 phosphomevalonate kinase Proteins 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- 230000002438 mitochondrial effect Effects 0.000 description 11
- 230000004888 barrier function Effects 0.000 description 10
- 235000012000 cholesterol Nutrition 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 108010032748 Cornified Envelope Proline-Rich Proteins Proteins 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 229940049964 oleate Drugs 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 102100035418 Ceramide synthase 4 Human genes 0.000 description 5
- 101710146190 Ceramide synthase 4 Proteins 0.000 description 5
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 5
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 230000009759 skin aging Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- ASKIVFGGGGIGKH-UHFFFAOYSA-N 2,3-dihydroxypropyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OCC(O)CO ASKIVFGGGGIGKH-UHFFFAOYSA-N 0.000 description 4
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 102100030291 Cornifin-B Human genes 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 102100031784 Loricrin Human genes 0.000 description 4
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 description 4
- 206010040844 Skin exfoliation Diseases 0.000 description 4
- 102000003705 Syndecan-1 Human genes 0.000 description 4
- 108090000058 Syndecan-1 Proteins 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- 150000003863 ammonium salts Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000001914 calming effect Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 125000005456 glyceride group Chemical group 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 108010079309 loricrin Proteins 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229920001296 polysiloxane Polymers 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 3
- 108010087410 3-dehydrosphinganine reductase Proteins 0.000 description 3
- 102100023340 3-ketodihydrosphingosine reductase Human genes 0.000 description 3
- 101710193701 ATP synthase subunit delta Proteins 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102000007356 Cornified Envelope Proline-Rich Proteins Human genes 0.000 description 3
- 102100028202 Cytochrome c oxidase subunit 6C Human genes 0.000 description 3
- 101710198061 Cytochrome c oxidase subunit 6C Proteins 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 101710091045 Envelope protein Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 102100034334 Fatty acid CoA ligase Acsl3 Human genes 0.000 description 3
- 101710131075 Fatty acid CoA ligase Acsl3 Proteins 0.000 description 3
- 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 3
- 102100034868 Kallikrein-5 Human genes 0.000 description 3
- 101710176223 Kallikrein-5 Proteins 0.000 description 3
- 101710159440 Long-chain-fatty-acid-CoA ligase 3 Proteins 0.000 description 3
- 102100022923 Phosphopantothenate-cysteine ligase Human genes 0.000 description 3
- 101710107870 Phosphopantothenate-cysteine ligase Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101710188315 Protein X Proteins 0.000 description 3
- 108010026552 Proteome Proteins 0.000 description 3
- 102100026259 Repetin Human genes 0.000 description 3
- 101710147968 Repetin Proteins 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 210000000736 corneocyte Anatomy 0.000 description 3
- 239000008406 cosmetic ingredient Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- 230000035618 desquamation Effects 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 239000010419 fine particle Substances 0.000 description 3
- 235000021588 free fatty acids Nutrition 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 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 3
- 230000000670 limiting effect Effects 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 3
- 230000036542 oxidative stress Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 201000004700 rosacea Diseases 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 150000003410 sphingosines Chemical class 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229940043375 1,5-pentanediol Drugs 0.000 description 2
- QHZLMUACJMDIAE-UHFFFAOYSA-N 1-monopalmitoylglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)CO QHZLMUACJMDIAE-UHFFFAOYSA-N 0.000 description 2
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- NCZPCONIKBICGS-UHFFFAOYSA-N 3-(2-ethylhexoxy)propane-1,2-diol Chemical compound CCCCC(CC)COCC(O)CO NCZPCONIKBICGS-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 2
- 102100032814 ATP-dependent zinc metalloprotease YME1L1 Human genes 0.000 description 2
- 101710161876 ATP-dependent zinc metalloprotease YME1L1 Proteins 0.000 description 2
- 108010049926 Acetate-CoA ligase Proteins 0.000 description 2
- 102000008146 Acetate-CoA ligase Human genes 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 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
- 241000283690 Bos taurus Species 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 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
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- 206010012444 Dermatitis diaper Diseases 0.000 description 2
- 208000003105 Diaper Rash Diseases 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 102100037009 Filaggrin-2 Human genes 0.000 description 2
- 101710095953 Filaggrin-2 Proteins 0.000 description 2
- 101000834118 Homo sapiens Malonate-CoA ligase ACSF3, mitochondrial Proteins 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 102000011782 Keratins Human genes 0.000 description 2
- 108010076876 Keratins Proteins 0.000 description 2
- 102100026665 Malonate-CoA ligase ACSF3, mitochondrial Human genes 0.000 description 2
- 108030000878 Malonate-CoA ligases Proteins 0.000 description 2
- 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 2
- 241001465754 Metazoa Species 0.000 description 2
- 101710127007 NAD-dependent malic enzyme Proteins 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000012641 Pigmentation disease Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 244000228451 Stevia rebaudiana Species 0.000 description 2
- 235000006092 Stevia rebaudiana Nutrition 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- OFUHPGMOWVHNPN-QWZFGMNQSA-N [(2r)-2,5,7,8-tetramethyl-2-[(4r,8r)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] (9z,12z)-octadeca-9,12-dienoate Chemical compound O1[C@](C)(CCC[C@H](C)CCC[C@H](C)CCCC(C)C)CCC2=C(C)C(OC(=O)CCCCCCC\C=C/C\C=C/CCCCC)=C(C)C(C)=C21 OFUHPGMOWVHNPN-QWZFGMNQSA-N 0.000 description 2
- 239000006096 absorbing agent Substances 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- 235000011399 aloe vera Nutrition 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 229940099583 aluminum starch octenylsuccinate Drugs 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 235000012745 brilliant blue FCF Nutrition 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000017455 cell-cell adhesion Effects 0.000 description 2
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 2
- 239000005516 coenzyme A Substances 0.000 description 2
- 229940093530 coenzyme a Drugs 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 208000010247 contact dermatitis Diseases 0.000 description 2
- 230000006003 cornification Effects 0.000 description 2
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 2
- 229940100524 ethylhexylglycerin Drugs 0.000 description 2
- 125000001924 fatty-acyl group Chemical group 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 108010033564 involucrin Proteins 0.000 description 2
- 102000007236 involucrin Human genes 0.000 description 2
- 239000002085 irritant Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 108010071421 milk fat globule Proteins 0.000 description 2
- KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 0.000 description 2
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- WCVRQHFDJLLWFE-UHFFFAOYSA-N pentane-1,2-diol Chemical compound CCCC(O)CO WCVRQHFDJLLWFE-UHFFFAOYSA-N 0.000 description 2
- 229960005323 phenoxyethanol Drugs 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000008263 repair mechanism Effects 0.000 description 2
- 230000035806 respiratory chain Effects 0.000 description 2
- 229940108325 retinyl palmitate Drugs 0.000 description 2
- 235000019172 retinyl palmitate Nutrition 0.000 description 2
- 239000011769 retinyl palmitate Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229920002545 silicone oil Polymers 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 210000000438 stratum basale Anatomy 0.000 description 2
- 230000008833 sun damage Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 229960005196 titanium dioxide Drugs 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-O triethanolammonium Chemical compound OCC[NH+](CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-O 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- WTVHAMTYZJGJLJ-UHFFFAOYSA-N (+)-(4S,8R)-8-epi-beta-bisabolol Natural products CC(C)=CCCC(C)C1(O)CCC(C)=CC1 WTVHAMTYZJGJLJ-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- RGZSQWQPBWRIAQ-CABCVRRESA-N (-)-alpha-Bisabolol Chemical compound CC(C)=CCC[C@](C)(O)[C@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-CABCVRRESA-N 0.000 description 1
- MPJMJSVSVMGORJ-QKKXKWKRSA-N (2S,3R,4S,5R,6R)-2-[(2R,3S,4R,5R)-6-fluoro-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound C1([C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO)F MPJMJSVSVMGORJ-QKKXKWKRSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- OKZYCXHTTZZYSK-ZCFIWIBFSA-N (R)-5-phosphomevalonic acid Chemical compound OC(=O)C[C@@](O)(C)CCOP(O)(O)=O OKZYCXHTTZZYSK-ZCFIWIBFSA-N 0.000 description 1
- KIHBGTRZFAVZRV-KRWDZBQOSA-N (S)-2-hydroxyoctadecanoic acid Chemical compound CCCCCCCCCCCCCCCC[C@H](O)C(O)=O KIHBGTRZFAVZRV-KRWDZBQOSA-N 0.000 description 1
- 229940015975 1,2-hexanediol Drugs 0.000 description 1
- QLAJNZSPVITUCQ-UHFFFAOYSA-N 1,3,2-dioxathietane 2,2-dioxide Chemical compound O=S1(=O)OCO1 QLAJNZSPVITUCQ-UHFFFAOYSA-N 0.000 description 1
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000006039 1-hexenyl group Chemical group 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
- JSOVGYMVTPPEND-UHFFFAOYSA-N 16-methylheptadecyl 2,2-dimethylpropanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)C(C)(C)C JSOVGYMVTPPEND-UHFFFAOYSA-N 0.000 description 1
- WNURHUNGASWDBR-UHFFFAOYSA-N 16-methylheptadecyl decanoate Chemical compound CCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC(C)C WNURHUNGASWDBR-UHFFFAOYSA-N 0.000 description 1
- VXXDXJJJTYQHPX-UHFFFAOYSA-N 2,2-bis(hydroxymethyl)propane-1,3-diol;2-ethyl-2-(hydroxymethyl)propane-1,3-diol Chemical class CCC(CO)(CO)CO.OCC(CO)(CO)CO VXXDXJJJTYQHPX-UHFFFAOYSA-N 0.000 description 1
- WMYINDVYGQKYMI-UHFFFAOYSA-N 2-[2,2-bis(hydroxymethyl)butoxymethyl]-2-ethylpropane-1,3-diol Chemical compound CCC(CO)(CO)COCC(CC)(CO)CO WMYINDVYGQKYMI-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- DSKYSDCYIODJPC-UHFFFAOYSA-N 2-butyl-2-ethylpropane-1,3-diol Chemical compound CCCCC(CC)(CO)CO DSKYSDCYIODJPC-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- JKRDADVRIYVCCY-UHFFFAOYSA-N 2-hydroxyoctanoic acid Chemical compound CCCCCCC(O)C(O)=O JKRDADVRIYVCCY-UHFFFAOYSA-N 0.000 description 1
- 125000006026 2-methyl-1-butenyl group Chemical group 0.000 description 1
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 1
- QWGRWMMWNDWRQN-UHFFFAOYSA-N 2-methylpropane-1,3-diol Chemical compound OCC(C)CO QWGRWMMWNDWRQN-UHFFFAOYSA-N 0.000 description 1
- GECRRQVLQHRVNH-MRCUWXFGSA-N 2-octyldodecyl (z)-octadec-9-enoate Chemical compound CCCCCCCCCCC(CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC GECRRQVLQHRVNH-MRCUWXFGSA-N 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- KBUNOSOGGAARKZ-KRWDZBQOSA-N 3-dehydrosphinganine Chemical compound CCCCCCCCCCCCCCCC(=O)[C@@H](N)CO KBUNOSOGGAARKZ-KRWDZBQOSA-N 0.000 description 1
- 125000006041 3-hexenyl group Chemical group 0.000 description 1
- 125000006027 3-methyl-1-butenyl group Chemical group 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 101150038907 ABCA12 gene Proteins 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 241001116389 Aloe Species 0.000 description 1
- 244000144927 Aloe barbadensis Species 0.000 description 1
- 235000002961 Aloe barbadensis Nutrition 0.000 description 1
- VMSBPMHUIPSRMV-UHFFFAOYSA-N C(CCCCCCC)C(O)C(C(O)CCCCCCCC)(C(O)CCCCCCCC)C(O)CCCCCCCC Chemical compound C(CCCCCCC)C(O)C(C(O)CCCCCCCC)(C(O)CCCCCCCC)C(O)CCCCCCCC VMSBPMHUIPSRMV-UHFFFAOYSA-N 0.000 description 1
- 101100150142 Caenorhabditis elegans sprr-2 gene Proteins 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 235000007866 Chamaemelum nobile Nutrition 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 240000008067 Cucumis sativus Species 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102400000011 Cytochrome b-c1 complex subunit 9 Human genes 0.000 description 1
- 101800000778 Cytochrome b-c1 complex subunit 9 Proteins 0.000 description 1
- 102100027456 Cytochrome c oxidase subunit 2 Human genes 0.000 description 1
- 101710091264 Cytochrome c oxidase subunit 2 Proteins 0.000 description 1
- 101710153216 Cytochrome c oxidase subunit NDUFA4 Proteins 0.000 description 1
- 102100023949 Cytochrome c oxidase subunit NDUFA4 Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 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
- AERBNCYCJBRYDG-UHFFFAOYSA-N D-ribo-phytosphingosine Natural products CCCCCCCCCCCCCCC(O)C(O)C(N)CO AERBNCYCJBRYDG-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102100028314 Filaggrin Human genes 0.000 description 1
- 101710088660 Filaggrin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 1
- 208000004898 Herpes Labialis Diseases 0.000 description 1
- 101000702152 Homo sapiens Cornifin-B Proteins 0.000 description 1
- 102000005298 Iron-Sulfur Proteins Human genes 0.000 description 1
- 108010081409 Iron-Sulfur Proteins Proteins 0.000 description 1
- MLSJBGYKDYSOAE-DCWMUDTNSA-N L-Ascorbic acid-2-glucoside Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1O MLSJBGYKDYSOAE-DCWMUDTNSA-N 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- LTYOQGRJFJAKNA-KKIMTKSISA-N Malonyl CoA Natural products S(C(=O)CC(=O)O)CCNC(=O)CCNC(=O)[C@@H](O)C(CO[P@](=O)(O[P@](=O)(OC[C@H]1[C@@H](OP(=O)(O)O)[C@@H](O)[C@@H](n2c3ncnc(N)c3nc2)O1)O)O)(C)C LTYOQGRJFJAKNA-KKIMTKSISA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 244000042664 Matricaria chamomilla Species 0.000 description 1
- 235000007232 Matricaria chamomilla Nutrition 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 102000006746 NADH Dehydrogenase Human genes 0.000 description 1
- 108010086428 NADH Dehydrogenase Proteins 0.000 description 1
- 102100026377 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 Human genes 0.000 description 1
- 101710192696 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 Proteins 0.000 description 1
- 101710098828 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2 Proteins 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 244000131316 Panax pseudoginseng Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropanol Chemical compound CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 102100030944 Protein-glutamine gamma-glutamyltransferase K Human genes 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 101000828726 Rattus norvegicus Cornifin-A Proteins 0.000 description 1
- VYGQUTWHTHXGQB-UHFFFAOYSA-N Retinol hexadecanoate Natural products CCCCCCCCCCCCCCCC(=O)OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-UHFFFAOYSA-N 0.000 description 1
- 102000002278 Ribosomal Proteins Human genes 0.000 description 1
- 108010000605 Ribosomal Proteins Proteins 0.000 description 1
- 241001303601 Rosacea Species 0.000 description 1
- 244000178231 Rosmarinus officinalis Species 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 240000001058 Sterculia urens Species 0.000 description 1
- 235000015125 Sterculia urens Nutrition 0.000 description 1
- FHNINJWBTRXEBC-UHFFFAOYSA-N Sudan III Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC(C=C1)=CC=C1N=NC1=CC=CC=C1 FHNINJWBTRXEBC-UHFFFAOYSA-N 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003571 Vitamin B5 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 208000000260 Warts Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 229910021536 Zeolite Inorganic materials 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- GANNOFFDYMSBSZ-UHFFFAOYSA-N [AlH3].[Mg] Chemical class [AlH3].[Mg] GANNOFFDYMSBSZ-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- CQPFMGBJSMSXLP-UHFFFAOYSA-M acid orange 7 Chemical compound [Na+].OC1=CC=C2C=CC=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 CQPFMGBJSMSXLP-UHFFFAOYSA-M 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 125000000304 alkynyl group Chemical group 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
- 229960000458 allantoin Drugs 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- RGZSQWQPBWRIAQ-LSDHHAIUSA-N alpha-Bisabolol Natural products CC(C)=CCC[C@@](C)(O)[C@@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-LSDHHAIUSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- CPLYLXYEVLGWFJ-UHFFFAOYSA-N alpha-hydroxyeicosanoic acid Natural products CCCCCCCCCCCCCCCCCCC(O)C(O)=O CPLYLXYEVLGWFJ-UHFFFAOYSA-N 0.000 description 1
- JYZJYKOZGGEXSX-UHFFFAOYSA-N alpha-hydroxytetradecanoic acid Natural products CCCCCCCCCCCCC(O)C(O)=O JYZJYKOZGGEXSX-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000000058 anti acne agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000001166 anti-perspirative effect Effects 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 230000002682 anti-psoriatic effect Effects 0.000 description 1
- 229940124340 antiacne agent Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940053195 antiepileptics hydantoin derivative Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940030225 antihemorrhagics Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003213 antiperspirant Substances 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 229940067599 ascorbyl glucoside Drugs 0.000 description 1
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 239000012754 barrier agent Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000002210 biocatalytic effect Effects 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229940036350 bisabolol Drugs 0.000 description 1
- HHGZABIIYIWLGA-UHFFFAOYSA-N bisabolol Natural products CC1CCC(C(C)(O)CCC=C(C)C)CC1 HHGZABIIYIWLGA-UHFFFAOYSA-N 0.000 description 1
- 238000004061 bleaching Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000011449 brick Substances 0.000 description 1
- 239000004161 brilliant blue FCF Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000015155 buttermilk Nutrition 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
- 208000020670 canker sore Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- CEZCCHQBSQPRMU-UHFFFAOYSA-L chembl174821 Chemical compound [Na+].[Na+].COC1=CC(S([O-])(=O)=O)=C(C)C=C1N=NC1=C(O)C=CC2=CC(S([O-])(=O)=O)=CC=C12 CEZCCHQBSQPRMU-UHFFFAOYSA-L 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 229940080421 coco glucoside Drugs 0.000 description 1
- 229940071160 cocoate Drugs 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000002247 constant time method Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229940075482 d & c green 5 Drugs 0.000 description 1
- 229940099441 d&c blue no. 4 Drugs 0.000 description 1
- 229940099449 d&c orange no. 4 Drugs 0.000 description 1
- 229940096890 d&c violet no. 2 Drugs 0.000 description 1
- 229940051157 d&c yellow no. 11 Drugs 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical class CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 239000007854 depigmenting agent Substances 0.000 description 1
- 230000002951 depilatory effect Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- KQVJZDZLEDQCSD-UHFFFAOYSA-H dialuminum;2-[[4-[ethyl-[(3-sulfonatophenyl)methyl]amino]phenyl]-[4-[ethyl-[(3-sulfonatophenyl)methyl]azaniumylidene]cyclohexa-2,5-dien-1-ylidene]methyl]benzenesulfonate Chemical compound [Al+3].[Al+3].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1.C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1.C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 KQVJZDZLEDQCSD-UHFFFAOYSA-H 0.000 description 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical class 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 1
- TVCBMJCHKADLEE-UHFFFAOYSA-N diazanium;2-[[4-[ethyl-[(4-sulfonatophenyl)methyl]amino]phenyl]-[4-[ethyl-[(4-sulfonatophenyl)methyl]azaniumylidene]cyclohexa-2,5-dien-1-ylidene]methyl]benzenesulfonate Chemical compound [NH4+].[NH4+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=CC(=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=C(S([O-])(=O)=O)C=C1 TVCBMJCHKADLEE-UHFFFAOYSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- OTKJDMGTUTTYMP-UHFFFAOYSA-N dihydrosphingosine Natural products CCCCCCCCCCCCCCCC(O)C(N)CO OTKJDMGTUTTYMP-UHFFFAOYSA-N 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- LQJVOKWHGUAUHK-UHFFFAOYSA-L disodium 5-amino-4-hydroxy-3-phenyldiazenylnaphthalene-2,7-disulfonate Chemical compound [Na+].[Na+].OC1=C2C(N)=CC(S([O-])(=O)=O)=CC2=CC(S([O-])(=O)=O)=C1N=NC1=CC=CC=C1 LQJVOKWHGUAUHK-UHFFFAOYSA-L 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- FPAYXBWMYIMERV-UHFFFAOYSA-L disodium;5-methyl-2-[[4-(4-methyl-2-sulfonatoanilino)-9,10-dioxoanthracen-1-yl]amino]benzenesulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=CC(C)=CC=C1NC(C=1C(=O)C2=CC=CC=C2C(=O)C=11)=CC=C1NC1=CC=C(C)C=C1S([O-])(=O)=O FPAYXBWMYIMERV-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- GPRNNOKYGIISIE-UHFFFAOYSA-N dodecyl pentanoate Chemical compound CCCCCCCCCCCCOC(=O)CCCC GPRNNOKYGIISIE-UHFFFAOYSA-N 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000004136 fatty acid synthesis Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 229910021485 fumed silica Inorganic materials 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 238000003633 gene expression assay Methods 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 229940080812 glyceryl caprate Drugs 0.000 description 1
- 229940087068 glyceryl caprylate Drugs 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000007954 growth retardant Substances 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 229940124563 hair growth stimulant Drugs 0.000 description 1
- 230000036074 healthy skin Effects 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 150000002398 hexadecan-1-ols Chemical class 0.000 description 1
- IZQGSFBPMUQBFC-UHFFFAOYSA-N hexadecyl 2,2-dimethylpropanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)C(C)(C)C IZQGSFBPMUQBFC-UHFFFAOYSA-N 0.000 description 1
- DWMMZQMXUWUJME-UHFFFAOYSA-N hexadecyl octanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)CCCCCCC DWMMZQMXUWUJME-UHFFFAOYSA-N 0.000 description 1
- IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 description 1
- FHKSXSQHXQEMOK-UHFFFAOYSA-N hexane-1,2-diol Chemical compound CCCCC(O)CO FHKSXSQHXQEMOK-UHFFFAOYSA-N 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 150000001469 hydantoins Chemical class 0.000 description 1
- ZCTXEAQXZGPWFG-UHFFFAOYSA-N imidurea Chemical compound O=C1NC(=O)N(CO)C1NC(=O)NCNC(=O)NC1C(=O)NC(=O)N1CO ZCTXEAQXZGPWFG-UHFFFAOYSA-N 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 208000001875 irritant dermatitis Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- PYIDGJJWBIBVIA-UYTYNIKBSA-N lauryl glucoside Chemical compound CCCCCCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O PYIDGJJWBIBVIA-UYTYNIKBSA-N 0.000 description 1
- 229940048848 lauryl glucoside Drugs 0.000 description 1
- 229940040102 levulinic acid Drugs 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940078752 magnesium ascorbyl phosphate Drugs 0.000 description 1
- 229960000869 magnesium oxide Drugs 0.000 description 1
- LTYOQGRJFJAKNA-DVVLENMVSA-N malonyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 LTYOQGRJFJAKNA-DVVLENMVSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229940031722 methyl gluceth-20 Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical compound OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 description 1
- 229940100573 methylpropanediol Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000008811 mitochondrial respiratory chain Effects 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- AEIJTFQOBWATKX-UHFFFAOYSA-N octane-1,2-diol Chemical compound CCCCCCC(O)CO AEIJTFQOBWATKX-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 229950009195 phenylpropanol Drugs 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000008832 photodamage Effects 0.000 description 1
- 230000002165 photosensitisation Effects 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- AERBNCYCJBRYDG-KSZLIROESA-N phytosphingosine Chemical compound CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@@H](N)CO AERBNCYCJBRYDG-KSZLIROESA-N 0.000 description 1
- 229940033329 phytosphingosine Drugs 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000223 polyglycerol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000009862 primary prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 238000000575 proteomic method Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 229940051201 quinoline yellow Drugs 0.000 description 1
- IZMJMCDDWKSTTK-UHFFFAOYSA-N quinoline yellow Chemical compound C1=CC=CC2=NC(C3C(C4=CC=CC=C4C3=O)=O)=CC=C21 IZMJMCDDWKSTTK-UHFFFAOYSA-N 0.000 description 1
- 235000012752 quinoline yellow Nutrition 0.000 description 1
- FZUOVNMHEAPVBW-UHFFFAOYSA-L quinoline yellow ws Chemical compound [Na+].[Na+].O=C1C2=CC=CC=C2C(=O)C1C1=NC2=C(S([O-])(=O)=O)C=C(S(=O)(=O)[O-])C=C2C=C1 FZUOVNMHEAPVBW-UHFFFAOYSA-L 0.000 description 1
- LKUNXBRZDFMZOK-UHFFFAOYSA-N rac-1-monodecanoylglycerol Chemical compound CCCCCCCCCC(=O)OCC(O)CO LKUNXBRZDFMZOK-UHFFFAOYSA-N 0.000 description 1
- GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 229940094944 saccharide isomerate Drugs 0.000 description 1
- 238000007665 sagging Methods 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000009863 secondary prevention Effects 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 230000037394 skin elasticity Effects 0.000 description 1
- 230000037393 skin firmness Effects 0.000 description 1
- 230000037067 skin hydration Effects 0.000 description 1
- 201000010153 skin papilloma Diseases 0.000 description 1
- 230000036560 skin regeneration Effects 0.000 description 1
- 229940080321 sodium anisate Drugs 0.000 description 1
- 229940080272 sodium coco-sulfate Drugs 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- 229940057950 sodium laureth sulfate Drugs 0.000 description 1
- 229940058349 sodium levulinate Drugs 0.000 description 1
- 229940102541 sodium trideceth sulfate Drugs 0.000 description 1
- SXHLENDCVBIJFO-UHFFFAOYSA-M sodium;2-[2-(2-dodecoxyethoxy)ethoxy]ethyl sulfate Chemical compound [Na+].CCCCCCCCCCCCOCCOCCOCCOS([O-])(=O)=O SXHLENDCVBIJFO-UHFFFAOYSA-M 0.000 description 1
- KLYDBHUQNXKACI-UHFFFAOYSA-M sodium;2-[2-(2-tridecoxyethoxy)ethoxy]ethyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCOCCOCCOCCOS([O-])(=O)=O KLYDBHUQNXKACI-UHFFFAOYSA-M 0.000 description 1
- AETSDHMVQHOYPB-UHFFFAOYSA-M sodium;4-methoxybenzoate Chemical compound [Na+].COC1=CC=C(C([O-])=O)C=C1 AETSDHMVQHOYPB-UHFFFAOYSA-M 0.000 description 1
- RDKYCKDVIYTSAJ-UHFFFAOYSA-M sodium;4-oxopentanoate Chemical compound [Na+].CC(=O)CCC([O-])=O RDKYCKDVIYTSAJ-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- LJFWQNJLLOFIJK-UHFFFAOYSA-N solvent violet 13 Chemical compound C1=CC(C)=CC=C1NC1=CC=C(O)C2=C1C(=O)C1=CC=CC=C1C2=O LJFWQNJLLOFIJK-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- OTKJDMGTUTTYMP-ZWKOTPCHSA-N sphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@@H](N)CO OTKJDMGTUTTYMP-ZWKOTPCHSA-N 0.000 description 1
- 125000002657 sphingoid group Chemical group 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 229940099373 sudan iii Drugs 0.000 description 1
- 230000036561 sun exposure Effects 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 108010058734 transglutaminase 1 Proteins 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 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
- 239000012588 trypsin Substances 0.000 description 1
- 229940035936 ubiquinone Drugs 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000036448 vitalisation Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000009492 vitamin B5 Nutrition 0.000 description 1
- 239000011675 vitamin B5 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 150000003700 vitamin C derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000004078 waterproofing Methods 0.000 description 1
- 239000003357 wound healing promoting agent Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/68—Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- 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
-
- 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
- A61Q19/004—Aftersun 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
- A61Q19/007—Preparations for dry 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
- A61Q19/08—Anti-ageing preparations
Definitions
- the present invention relates to a topical composition and to a cosmetic or medical use of a topical composition.
- the skin is a critical barrier for the body. It prevents the loss of water and electrolytes and acts as a barrier to external assaults on the body, such as from ultra-violet light, pollution, infectious agents, etc.
- the epidermis, or outer portion of the skin provides the primary barrier function of the skin.
- the epidermis is made up of layers of which the stratum comeum is the outermost layer and the stratum basale is the innermost layer.
- the epidermis contains no blood vessels, and cells in the deepest layers are nourished by diffusion from blood capillaries extending to the upper layers of the dermis.
- the stratum basale of the epidermis contains keratinocytes which proliferate through mitosis.
- the daughter cells move up through the layers of the epidermis, changing shape and composition as they undergo multiple stages of cell differentiation.
- the daughter cells eventually become terminally differentiated when they reach the stratum comeum.
- the terminally differentiated keratinocytes are referred to as comeocytes.
- the corneocytes are filled with water-retaining keratin proteins and are attached together through comeodesmosomes. Comeocytes do not contain a nucleus.
- the comeocytes are eventually shed from the surface of the skin, a process called desquamation.
- the stratum corneum acts as the main barrier in the skin. It is made up of about 10 to 30 layers of comeocytes surrounded by lipid layers (lipid lamellae). The stratum comeum is thus described as a wall composed of bricks (comeocytes) and mortar (lipids). The main constituents of the lipid layers are ceramides, cholesterol, and free fatty acids in a 1:1:1 molar ratio. The ceramides play the most important role in the barrier function of the stratum comeum. Dismption or decrease of ceramides in the stratum corneum weakens the skin barrier function, thereby e.g. increasing transdermal water loss.
- ceramide composition of the skin has generally involved incorporation of ceramides or pseudo-ceramides into topical skincare formulations.
- ceramides are highly insoluble and have high melting points. This makes formulation difficult. Also, their tendency to recrystallise complicates their stable incorporation into topical formulations.
- Efforts to overcome formulation difficulties have generally focussed on combining ceramides with other lipids. For example, WO 1999029293 describes a combination of a free sphingoid base and a ceramide.
- WO2018177730 describes melting a mixture of, or a wax and a ceramide, and then incorporating the melt into an oil-containing formulation.
- MSEF milk sphingolipid-enriched fraction
- An alternative approach to modulate the ceramide composition of the stratum corneum is to apply a composition which induces epidermal lipid production and ceramides in particular.
- a composition which induces epidermal lipid production and ceramides in particular.
- application of an oat oil extract on keratinocytes is reported to increase lipid synthesis including ceramides; potentially through activation of peroxisome proliferator- activated receptors (Chon et al, Exp. Dermatol, 2015).
- compositions that comprise ceramide species that are stereochemically and structurally identical to those found in the human stratum corneum.
- the present invention relates to topical compositions comprising (glyco)sphingolipids and/or (glyco)ceramides that can be used in cosmetic and medical applications.
- the present invention comprises the following aspects:
- a topical composition comprising one or more compounds of formula I
- X is hydrogen or a glycosyl moiety, the carbon-carbon bond noted - is a double or a single bond,
- R 1 is an alkyl chain having 10 - 20 carbon atoms
- R 2 is hydrogen or a substituted or unsubstituted acyl having 16-34 carbon atoms
- R 3 is hydrogen when the carbon-carbon bond noted - is a double or a single bond, and R 3 is -OH when the carbon-carbon bond noted - is a single bond,
- R 4 is hydrogen when the carbon-carbon bond noted - is a double or a single bond, and R 4 is hydrogen or -OH when the carbon-carbon bond noted - is a double bond, said composition is characterized in that at least one of the one or more compounds of formula I has a lactosyl moiety or a glucosyl moiety in the position X.
- Topical compositions comprising one or more compounds of formula I administered onto skin of an individual for a period of time increase the ceramide content of the stratum corneum, increase keratinocyte terminal differentiation in the epidermis, upregulate enzymes in the epidermis associated with epidermal ceramide synthesis, and/or improve skin barrier function in said individual.
- Beneficial effects cosmetic treatment with topical compositions comprising one or more compounds of formula I are one or more of following Improving skin complexion;
- compositions comprising one or more compounds of formula I for use in treating a skin pathological condition or a skin disease in an individual, such as acne, ichthyosis, xeroderma, eczema, atopic dermatitis and/or psoriasis.
- Method for non-pharmacological intervention for mitigation of a skin condition or a skin disease in an individual who has, or who is susceptible to developing an impaired skin barrier function comprising topically administering a composition comprising one or more compounds of formula I onto skin of an individual.
- Figures 1 to 5 show heatmaps using a log2 scale with up- or downregulation of respective proteins upon treatment with 0,01 % (01), 0,03 % (03) and 0,15 % (15) of respective ceramide in vehicle as compared to vehicle without ceramide (VEH)
- Fig. 1 LacCerNS
- Fig. 2 GlcCerNS
- Fig. 3 CerNP
- Fig. 4 CerNG
- Fig. 5 CerNS
- one or more compounds of formula I may achieve this by upregulating enzymes in the epidermis associated with epidermal ceramide synthesis. Further, one or more compounds of formula I advantageously increase keratinocyte terminal differentiation in the epidermis and improve skin barrier function in skin of an individual.
- the following terms have the following meanings:
- Topical composition includes compositions suitable for topical application on keratinous tissue, especially on skin. Such compositions are typically dermatologically acceptable in that they do not have undue toxicity, incompatibility, instability, allergic response, and the like, when applied to skin. Topical compositions typically comprise a topically acceptable carrier. Topical skin care compositions of the present invention can have a selected viscosity to avoid significant dripping or pooling after application to skin. Accordingly, a topical cosmetic or medical composition of the invention comprising one or more compounds described herein, would typically comprise one or more other compounds that are useful for formulating these compositions. Typically, such “formulating” compounds do not possess the biological activity of the compounds of the invention.
- Keratinous tissue includes keratin-containing layers disposed as the outermost protective covering of mammals and includes, but is not limited to, lips, skin, hair and nails.
- reducing or any variation of the term such as “reduction” includes any measurable decrease to achieve a desired effect.
- Effective amount means an amount sufficient to render a desired treatment or management outcome in a human. An effective amount can be administered in one or more doses to achieve the desired treatment or management outcome.
- Preventive treatment means treatment given or action taken to diminish the risk of onset or recurrence of a cosmetic or medical condition, or of an effect related to an impairment in the visual appearance of a skin or of a skin disease.
- Primary prevention means prevention of the initial onset of a cosmetic or a medical condition in an individual.
- “Secondary prevention” means, in an individual who has a cosmetic or a medical condition or who has had a condition, (i) prevention of reoccurrence of the condition, (ii) increase in the duration of remission of the condition, and/or (iii) reduction in severity of symptoms of the condition.
- Treat means to address a cosmetic or a medical condition or disease with the objective of improving or stabilising an outcome in the person being treated or addressing an underlying need. Treat therefore includes the topical management of the cosmetic or medical condition or disease by addressing dermatological needs of the person being treated. “Treating” and “treatment” have grammatically corresponding meanings.
- “Therapy” means treatment given or action taken to reduce or eliminate symptoms of a disease or pathological condition.
- a child as referred to herein denotes a human individual until the age of 12.
- a teenager as referred to herein denotes a human individual having an age of between 13 and
- the present invention relates to a topical composition
- a topical composition comprising one or more compounds of formula I I, wherein
- X is hydrogen or a glycosyl moiety, the carbon-carbon bond noted - is a double or a single bond,
- R 1 is an alkyl chain having 10 - 20 carbon atoms
- R 2 is hydrogen or a substituted or unsubstituted acyl having 16-34 carbon atoms
- R 3 is hydrogen when the carbon-carbon bond noted - is a double or a single bond, and R 3 is -OH when the carbon-carbon bond noted - is a single bond,
- R 4 is hydrogen when the carbon-carbon bond noted - is a double or a single bond, and R 4 is hydrogen or -OH when the carbon-carbon bond noted - is a double bond, said composition is characterized in that at least one of the one or more compounds of formula I has a lactosyl moiety or a glucosyl moiety in the position X.
- alkyl refers to an acyclic straight hydrocarbyl group in which the carbon atoms may be saturated or contain one or more double and/or triple bonds (so, forming for example an alkenyl or an alkynyl).
- alkyl examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, isobutyl, n-butyl, sec -butyl, tert-butyl, isopentyl, n-pentyl, neo-pentyl, n-hexyl, ethenyl, propenyl, 1-butenyl, 2-butenyl, isobutenyl,l-pentenyl, 2-pentenyl, 2-methyl- 1-butenyl, 3 -methyl- 1-butenyl, 2-methyl-2- butenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, methylpentenyl, dimethylbutenyl, ethynyl, propynyl, 1-butynyl, 2-butynyl, pentynyl, and hexynyl.
- alkyl examples include,
- acyl includes both saturated groups and groups having one or more double and/or triple bonds.
- substituted means that the carbon atoms may be substituted one or several times, preferably 1 to 3 times, with functional group(s).
- R 2 of compound I is an unsubstituted acyl group.
- R 2 of compound I or II is a saturated fatty acyl group or a fatty acyl group having one or more double bonds.
- the compounds of formula I may be obtained by any technique known to the skilled person.
- the compounds of formula I may be obtained by a fermentation technique or by a biocatalytic process.
- glycosphingoplipids such as lactosylceramide may be produced starting from the respective glycosyl fluoride, such as lactosyl fluoride, followed by coupling to a (acylated) sphingoid base by the use of an endoglycoceramide synthase, such as described in Rich et al., ChemComm (2011) 47:10806-10808.
- Sphingoid bases may be produced by a fermentation process, such as e.g. described in WO 95/12683 Al, especially phytosphingosine or a precursor thereof (claim 1 of EP 0726 960 Bl).
- the topical composition comprises one or more compounds of formula I, wherein the residue X is lactosyl.
- the topical composition comprises at least two compounds of formula I, wherein for one compound of formula I the residue X is lactosyl and for the other compound of formula I the residue X is galactosyl.
- the topical composition comprises at least two compounds of formula I, wherein for one compound of formula I the residue X is lactosyl and for the other compound of formula I the residue X is hydrogen.
- the topical composition comprises at least two compounds of formula I, wherein for one compound of formula I the residue X is lactosyl and for the other compound of formula I the residue X is glucosyl.
- the topical composition comprises at least three compounds of formula I, wherein for one compound of formula I the residue X is lactosyl for the second compound of formula I the residue X is galactosyl and for the third compound of formula I the residue X is glucosyl.
- the topical composition comprises at least three compounds of formula I, wherein for one compound of formula I the residue X is lactosyl, for the second compound of formula I the residue X is galactosyl, and for the third compound of formula I the residue X is hydrogen.
- the topical composition comprises at least three compounds of formula I, wherein for one compound of formula I the residue X is lactosyl, for the second compound of formula I the residue X is hydrogen, and for the third compound of formula I the residue X is glucosyl.
- the topical composition comprises at least four compounds of formula I, wherein for one compound of formula I the residue X is lactosyl for the second compound of formula I the residue X is hydrogen, for the third compound of formula I the residue X is glucosyl, and for the fourth compound of formula I the residue X is galactosyl.
- R 1 is -C12H25 and R 2 is hexadecanoyl, 2-hydroxyhexadecanoyl, octadecanoyl, 2- hydroxyoctadecanoyl, eicosanoyl, 2-hydroxyeicosanoyl, lignoceroyl, 2-hydroxytetracosanoyl or 30-(linoleyloxy)-triacontanoyl, preferably octadecanoyl or lignoceroyl.
- the one or more compounds of formula I may be formulated into topical compositions suitable for application to the skin.
- the topical compositions of the present invention will contain from about 0,0001 % to about 10% wt/wt of a compound of formula I, such as from about 0,005 % to about 5% wt/wt of a compound of formula I, or from 0,01 % to about 1% wt/wt of a compound of formula I.
- the topical compositions of the present invention may contain from about 0,0001 to about 0,00025 % wt/wt of a compound of formula I, from about 0,0002 to about 0,0004 % wt/wt of a compound of formula I, from about 0,0003 to about 0,0005 % wt/wt of a compound of formula I, from about 0,0004 to about 0,0006 % wt/wt of a compound of formula I, from about 0,0005 to about 0,0008 % wt/wt of a compound of formula I, from about 0,0007 to about 0,001 % wt/wt of a compound of formula I, from about 0,001 to about 0,005 % wt/wt of a compound of formula I, from about 0,003 to about 0,008 % wt/wt of a compound of formula I, from about 0,005 to about 0,01 % wt/wt of a compound of formula I, from about 0,008 to about 0,0505
- the topical compositions of the present invention contain an amount of about 0.01 % to 5% wt/wt of a compound of formula I. or an amount of about 0.02 % wt/wt to 1% wt/wt of a compound of formula I.
- Examples are 0.05 % wt/wt, 0.1 % wt/wt or 0.2 % wt/wt of a compound of formula I.
- Compounds of formula I in which the residue X is a glycosyl moiety selected from lactosyl, glucosyl and galactosyl may be present in an amount of 0.1 % wt/wt.
- Compounds of formula I in which the residue X is hydrogen may be present in an amount of 0.2 % wt/wt.
- the topical compositions can contain an amount of about 5 % to 10 % wt/wt of a compound of formula I.
- the topical compositions according to the present invention may comprise a single compound of formula I, e.g. a compound comprising the lactosyl moiety in position X of formula I, in the ranges or amounts as listed above.
- the topical composition according to the present invention comprises more than one compound of formula I, also termed herein as blend of compounds of formula I
- each compound of formula I may be present in the same amount or in different amounts.
- the ranges or amounts as listed above may relate to the total content of the blend in the topical composition, or to the amount of one compound in the blend in the topical composition.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0, 1 % wt/wt, wherein the blend has glucosylceramide in an amount of 0,02 % wt/wt and lactosylceramide in an amount of 0,08 % wt/wt.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0,2 % wt/wt, wherein the blend has lactosylceramide in an amount of 0,04 % wt/wt and ceramide NP in an amount of 0,16 % wt/wt.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0,2 % wt/wt, wherein the blend has lactosylceramide in an amount of 0,04 % wt/wt and ceramide NS in an amount of 0,16 % wt/wt.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0,2 % wt/wt, wherein the blend has lactosylceramide in an amount of 0,04 % wt/wt and ceramide NG in an amount of 0,16 % wt/wt.
- Non-limiting exemplary embodiments are also depicted in Example 1.
- the topical composition may comprise a blend of compounds of formula I, wherein X is hydrogen.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0, 1 % wt/wt, wherein the blend has ceramide NP in an amount of 0,06 % wt/wt, ceramide NS in an amount of 0,02 % wt/wt and ceramide NG in an amount of 0,02 % wt/wt.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0,2 % wt/wt, wherein the blend has ceramide NP in an amount of 0,11 % wt/wt, ceramide NS in an amount of 0,04 % wt/wt and ceramide NG in an amount of 0,05 % wt/wt.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0,5 % wt/wt, wherein the blend has ceramide NP in an amount of 0,28 % wt/wt, ceramide NS in an amount of 0,09 % wt/wt and ceramide NG in an amount of 0,13 % wt/wt.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0,1 % wt/wt, wherein the blend has ceramide NP in an amount of 0,075 % wt/wt, ceramide NS in an amount of 0,02 % wt/wt and ceramide NG in an amount of 0,005 % wt/wt.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0,2 % wt/wt, wherein the blend has ceramide NP in an amount of 0,15 % wt/wt, ceramide NS in an amount of 0,04 % wt/wt and ceramide NG in an amount of 0,01 % wt/wt.
- the topical composition may comprise a blend of compounds of formula I with a total content of the blend of 0,2 % wt/wt, wherein the blend has ceramide NP in an amount of 0,1 % wt/wt, ceramide NS in an amount of 0,05 % wt/wt and glucosylceramide in an amount of 0,05 % wt/wt.
- ceramide NP in an amount of 0,1 % wt/wt
- ceramide NS in an amount of 0,05 % wt/wt
- glucosylceramide in an amount of 0,05 % wt/wt.
- the amount of the one or more compounds of formula I in a composition of the invention may vary depending upon factors such as the age of the person, the risk and severity of any underlying condition, the environment the person is exposed to, the form of the topical composition, its use for cosmetic or medical purposes, and any other skin care compositions being administered. Appropriate doses for any particular person or indication may be determined by methods known to skin care practitioners. The dose may also vary depending upon whether the topical composition is a “leave on” or “rinse off’ formulation with “rinse off’ formulations generally containing lower doses. Further, the dose may vary depending on whether the topical composition is applied in an intervention treatment phase or in a maintenance phase. Generally higher doses can be applied in an initial intervention phase than in a maintenance phase.
- Topical composition according to the present invention may have a pH in the range of about 4.5 to about 8, e.g. from about 4.5 to about 6.
- Topical compositions of the present invention can be structured or formulated into a variety of different forms.
- Non-limiting examples include emulsions (e.g., water-in-oil, water-in-oil- in-water, oil-in-water, silicone-in-water, water-in-silicone, oil-in-water-in-oil, oil-in-water-in- silicone emulsions), creams, lotions, solutions (both aqueous and hydroalcoholic), anhydrous bases (such as lipsticks and powders), gels, masks, peelings, and ointments. Variations and other structures will be apparent to the skilled artisan and are appropriate for use in the present invention.
- a topical composition may be formulated as an emulsion.
- a topical composition of the present invention is typically intended for application on the face, on the body and/or on the hair.
- the topical composition may be for application on the face or on the body.
- a topical composition of the present invention may comprise a compound of formula I, which is selected from the group consisting of ceramide NS (CerNS or CNS), ceramide NG (CerNG or CNG), ceramide NP (CerNP or CNP), glucosyl ceramide or lactosyl ceramide, or a combination thereof.
- Ceramide NS, ceramide NdS and ceramide NP are named according to the shorthand nomenclature developed by Motta et al., Biochim Biophys Acta., 1993, 1182:147-151 and expanded by Rabionet et al., Biochim Biophys Acta, 2014, 1841:422-434, and by Masukawa et al., Journal of Lipid Research , 2008, 49, 1466-1476. Ceramides NdS may also be referred to as ceramide NG. For each species, the number of carbons and unsaturations (if present) may be expressed in parentheses following the letters of N, A, E, and O.
- the carbon chain length of the sphingoid base moiety of the ceramides mentioned herein is typically Cis.
- the carbon chain length of the acyl moiety of the ceramides mentioned herein may be e.g. Ci6, Cis, C20, C22 or C24.
- the glucosyl ceramide and the lactosyl ceramide as mentioned herein are preferably ceramide NS, typically with an acyl chain length of Cis.
- Glucosyl ceramide which is ceramide NS and has an acyl chain length of Cis may be referred to herein also as GlcCNS.
- Lactosyl ceramide which is ceramide NS and has an acyl chain length of Cis may be referred to herein also as LacCNS.
- a topical composition described herein on skin of an individual increases the ceramide content of the stratum corneum, increases keratinocyte terminal differentiation in the epidermis, upregulates enzymes in the epidermis associated with epidermal ceramide synthesis and/or improves skin barrier function in said individual.
- These effects may be determined by an upregulation of respective differentiation markers in vitro.
- an increase of keratinocyte terminal differentiation in the epidermis may be determined by an upregulation of differentiation markers such as loricrin, filaggrin or involucrin.
- Upregulation of enzymes in the epidermis associated with epidermal ceramide synthesis may be e.g. measured in vitro in keratinocytes as explained in Example 4.
- the effects may also be measured with further other suitable standard technique known to the skilled person.
- An increase of the ceramide content of the stratum corneum can be e.g. determined with the tape stripping procedure as e.g. described in Lademann et ah, European Journal of Pharmaceutics and Biopharmaceutics (2009) 72:317-323.
- An improvement of skin barrier function may be e.g. determined by measuring TEWL and skin hydration with a corneometer or tewameter.
- a topical composition of the present invention may advantageously be used for cosmetic treatment or medical treatment of keratinous tissue, especially skin, of an individual.
- the topical composition according to the invention may be referred to as topical cosmetic composition or cosmetic composition.
- Cosmetic treatment is herein defined as to improve the visual appearance of skin of the treated individual.
- improved visual appearance of skin is meant that cosmetic treatment with a topical composition of the invention comprising one or more compounds of formular I, in particular comprising one or more of the following beneficial effects on the treated skin of an individual: reducing skin roughness. reducing skin flakiness. reducing the depth of wrinkles in the skin. strengthening the skin elasticity. increasing the tautness of the skin. increasing the thickness of the skin. increasing skin moisture. calming irritated skin normalizing and improving the skin tone.
- the cosmetic compositions of the invention preferably improve skin complexion, i.e. color and texture of the skin, especially on the face; improve skin radiance, i.e. skin tone, luminosity, firmness, and discolouration (think dark circles and sun damage); improve skin tone, i.e. normalizing natural hue of the skin, reducing redness and reducing pigmentation; soothe the skin, i.e. calming irritated skin, e.g.
- mitigating, assuaging, or allaying pain from sunburning or dehydrating of the skin reduce the signs of skin ageing, both chronological and premature, e.g the signs of ageing due to exposure of the skin to intrinsic and extrinsic factors, like decrease in production of essential molecules supporting the skin natural structure, loss of water, UV light damage, or exposure to chemical internal radicals generated in the body (due to unhealthy eating or life style, a disease, etc) or external pollutants hazardous for the skin; and/or smooth skin wrinkles, in particular, the face skin wrinkles, both fine surface lines and deeper furrows, i.e. lessen the appearance of wrinkled skin, smoothing the skin surface;
- cosmetic compositions of the invention support and enhance healthy look of the skin, especially of the face and neck skin.
- the skin may be an aged and/or a dry skin.
- the cause of dryness of the skin may be of constitutional or acquired type.
- Non-pathological acquired constitutional dry skin can be characterized by a deficiency in lipids constituting the barrier and/or the aqueous-lipid film, and/or an endogenous insufficiency of sebum production by the sebaceous glands.
- Skin aging is a complex phenomenon responsible for progressive changes of the skin. Many factors contribute to skin aging and associated alterations in appearance and function of the skin, such as the actual age of a person, the amount of exposure to environmental factors (e.g., sun light, pollution, chemicals, smoke, etc.), and how well a person has taken care of their skin. In particular, skin aging concerns two processes - intrinsic aging, which is related to the natural aging process and genetic influences, and extrinsic aging, which is accumulated damage due to exposure to environmental factors.
- Intrinsic aging process in cells and skin can be related to the loss of proper function of the skin in maintaining biochemical pathways. Such pathways can control the oxidative/reductive environment balance in the skin, the regulation of inflammation, and the maintenance of the moisture balance of the skin. Losses of proper function of the skin can lead to increased oxidative damage, increased inflammation, dry skin, loss of skin firmness, increased skin unevenness, and increased fine lines and wrinkles.
- UV Factors that cause extrinsic aging can include exposure to ultraviolet (UV) rays, irritants, and pollutants, such as Polycyclic aromatic pollutants (PAH), Particulate Matter PM2.5 (micrometers), blue light, Ozone, or cigarette smoke.
- UV rays through sun exposure or the use of ultraviolet lamps (for example, tanning beds), can induce oxidative stress, inflammation, production of melanin, and even genetic mutations that leads to skin damage.
- the accumulation of oxidative stress through free radical formation can damage skin proteins leading to skin aging, which includes loss of elasticity, loss of dermal proteins, lines and wrinkles, and abnormal pigmentation.
- accumulation of fine particles such as PM 2.5 (fine particles that have an aerodynamic diameter under 2.5 pm) on the skin can also induce oxidative stress and inflammation. These fine particles may also cause damage on barrier proteins of the skin, leading to loss of moisture and elasticity of the skin.
- the appearance of aged skin targeted by the invention include thinning of the skin, a loss of firmness, a loss of elasticity, a loss of density or a loss of tonicity of the skin, the appearance of a marked microrelief of the skin, the appearance of roughness, the formation and/or presence of fine lines and/or of wrinkles, a modification of the radiance of the skin complexion, a wizened appearance of the skin, sagging of the skin, and/or withering of the skin.
- the cosmetic treatment according to the present invention typically has one or more beneficial effects on skin of an individual. These beneficial effects include one or more of improving skin complexion, improving skin radiance, improving skin tone, skin soothing, reducing premature skin aging, wrinkle smoothing and/or supporting healthy look of skin.
- Skin soothing or skin calming as used herein denote protection from skin irritation or reduction of skin irritation and typically has a gentle calming effect. Additionally to the above described biological effects, the present inventors have surprisingly found that application of lactosylceramide on the skin leads to an upregulation of syndecan-1, of ceramide synthase 4 and of phosphomevalonate kinase.
- Syndecan-1 is known to play a role in keratinocyte proliferation and differentiation.
- Ceramide synthase 4 catalyzes the formation of ceramides.
- Phosphomevalonate kinase is involved in cholesterol synthesis.
- the present invention relates to the use of lactosylceramide for increasing the ceramide content of the stratum corneum, increasing keratinocyte terminal differentiation in the epidermis, upregulating enzymes in the epidermis associated with epidermal ceramide synthesis and/or improving skin barrier function in skin of an individual.
- the present inventors have surprisingly found that application of ceramide NP on the skin leads to an upregulation of syndecan-1, long-chain-fatty-acid-CoA ligase 3, phosphopantothenate-cysteine ligase and phosphomevalonate kinase.
- Long-chain-fatty-acid-CoA ligase 3 activates long-chain fatty acids for synthesis of cellular lipids.
- Phosphopantothenate-cysteine ligase catalyzes the second step in the biosynthesis of coenzyme A from vitamin B5.
- Coenzyme A is a very important molecule in lipid metabolism, it is converted to acetyl-CoA, which is a precursor in the synthesis of fatty acids, cholesterol and ceramides.
- acetyl-CoA is a precursor in the synthesis of fatty acids, cholesterol and ceramides.
- ceramide NP may help to provide free fatty acids, cholesterol and ceramides to maintain the skin barrier.
- the present invention additionally relates to the use of ceramide NP for increasing the ceramide content of the stratum comeum, increasing keratinocyte terminal differentiation in the epidermis, upregulating enzymes in the epidermis associated with epidermal ceramide synthesis and/or improving skin barrier function in skin of an individual.
- the present inventors have also surprisingly found that application of ceramide NG on the skin leads to an upregulation of ceramide synthase 4, of loricrin, of repetin, of small proline- rich protein 2D and of phosphomevalonate kinase.
- Loricrin is a major keratinocyte cell envelope protein.
- Repetin is involved in the cornified cell envelope formation.
- Small proline rich protein 2D is a cross-linked envelope protein of keratinocytes.
- Cornification is an essential process to build the skin barrier, during which the cell membrane of keratinocytes is replaced by the cornified envelope.
- the cornified envelope is an agglomeration of several structural proteins that are crosslinked. Loricrin (makes up to 70-80 % of protein content of cornified envelope), repetin & small proline-rich protein 2d are part of the cornified envelope and their upregulation indicates that ceramide NG triggers the formation of the cornified envelope and therefore the keratinocyte terminal differentiation and may improve the skin barrier function.
- Ceramide Synthase 4 catalyzes the formation of ceramides and phosphomevalonate kinase is involved in cholesterol synthesis.
- the upregulation of both enzymes indicates that ceramide NG helps to provide cholesterol and ceramides to maintain the skin barrier.
- the present invention in one aspect relates to the use of ceramide NG for increasing the ceramide content of the stratum comeum, increasing keratinocyte terminal differentiation in the epidermis, upregulating enzymes in the epidermis associated with epidermal ceramide synthesis and/or improving skin barrier function in skin of an individual.
- the present inventors have surprisingly found that application of glucosyl ceramide on the skin leads to an upregulation of 3-ketodihydrosphingosine reductase, of acetyl-coenzyme A synthetase (cytoplasmic), of malonate-CoA ligase ACSF3 (mitochondrial) and of pho sphomevalonate .
- 3-ketodihydrosphingosine reductase kinase catalyzes the reduction of 3- ketodihydrosphingosine to dihydro sphingo sine.
- Acetyl-coenzyme A synthetase catalyzes the synthesis of acetyl-CoA from short-chain fatty acids.
- Malonate— CoA ligase ACSF3 catalyzes the initial reaction in intramitochondrial fatty acid synthesis, by activating malonate and methylmalonate into their respective CoA thioester.
- Acetyl- CoA and Malonyl-CoA are both precursors of the synthesis of fatty acids, cholesterol and ceramides.
- the Phosphomevalonate kinase is involved in the cholesterol synthesis and 3- ketodihydrosphingosine reductase in the ceramide synthesis.
- the upregulation of those enzymes indicates that glucosyl ceramide CNS helps to provide free fatty acids, cholesterol and ceramides to maintain the skin barrier.
- the present invention relates to the use of glucosyl ceramide for increasing the ceramide content of the stratum corneum, upregulating enzymes in the epidermis associated with epidermal ceramide synthesis and/or improving skin barrier function in skin of an individual.
- ceramide NS on the skin leads to an upregulation of cornifin-B, of filaggrin-2, of syndecan-1, of kallikrein-5 and of phosphomevalonate kinase.
- Cornifin-B is a cross-linked envelope protein of keratinocytes.
- Filaggrin-2 is important for proper integrity and mechanical strength of the stratum corneum of the epidermis, Essential for normal cell-cell adhesion in the cornified cell layers.
- Kallikrein-5 is a protease that cleaves corneodesmosomes.
- the cornification is an essential process to build the skin barrier, during which the cell membrane of keratinocytes is displaced by the cornified envelope.
- the cornified envelope is an agglomeration of several structural proteins that are crosslinked.
- Cornifin-B and Fillagrin- 2 are both parts of the cornified envelope and their upregulation indicates that ceramide NS may trigger the formation of the cornified envelope and therefore may improve the skin barrier function.
- Desquamation is the last step of the keratinocytes terminal differentiation and Kallikrein-5 is a protease that cleaves the corneodesmosomes (cell-cell-adhesion of corneocytes) allowing the corneocytes to desquame.
- Kallikrein-5 is a protease that cleaves the corneodesmosomes (cell-cell-adhesion of corneocytes) allowing the corneocytes to desquame.
- the present invention relates to the use of ceramide NS for increasing keratinocyte terminal differentiation in the epidermis and/or improving skin barrier function in skin of an individual.
- topical compositions according to the present invention may be used for medical treatment of skin of an individual.
- the topical composition according to the invention may be referred to as a topical pharmaceutical composition or a pharmaceutical composition.
- the pharmaceutical composition is for use in treating of a skin disease or of a skin pathological condition in an individual.
- skin disease is a disorder of structure or function in a human or animal that produces specific symptoms or that affects a specific location, i.e. skin, and is not simply a direct result of physical injury.
- skin diseases include acne, rosacea, erythrocouperosis, psoriasis, xeroderma, ichthyosis, vascular disorders, diaper rash, atopic dermatitis, eczema, contact dermatitis, irritant dermatitis, allergic dermatitis, seborrheic dermatitis.
- pathological skin condition refers to abnormal anatomical or physiological conditions and objective or subjective manifestations of disease, not classified as disease or syndrome.
- pathological skin conditions include: rosacea, which is characterized by small, red, pus-fil led bumps on the face and vitiligo, which results in large, irregular patches of skin.
- a pharmaceutical composition of the present invention may in some embodiments consist of one or more compounds of formula I of the inventive topical composition (as any of the described above).
- the topical pharmaceutical composition of the present invention may further include an additional ingredient that is pharmaceutically active for treating a skin disease or a pathological skin condition.
- Non-limiting examples of such additional pharmaceutical active agents include anti-acne agents, agents used to treat rosacea, analgesics, anesthetics, anorectals, antihistamines, anti inflammatory agents including non-steroidal anti-inflammatory drugs, antibiotics, antifungals, antivirals, antimicrobials, anti-cancer actives, scabicides, pediculicides, antineoplastics, antiperspirants, antipruritics, antipsoriatic agents, antiseborrheic agents, biologically active proteins and peptides, burn treatment agents, cauterizing agents, depigmenting agents, depilatories, diaper rash treatment agents, enzymes, hair growth stimulants, hair growth retardants including DFMO and its salts and analogs, hemostatics, kerotolytics, canker sore treatment agents, cold sore treatment agents, dental and periodontal treatment agents, photosensitizing actives, skin protectant/barrier agents, steroids including hormones and corticosteroids, sun
- Topical compositions of the invention may be advantageously administered onto skin of an individual for at least 7 days, such as for at least 14 days or for at least 21 days.
- the topical composition is administered for at least 28 days.
- the administration period of a cosmetic compositions of the invention there is no time limitation for the administration period of a cosmetic compositions of the invention.
- the administration period would be typically determined by a medical practitioner for each individual patient.
- a topical composition (either cosmetic or pharmaceutical) may be administered one time or several times per day, such as 2-3 times per day.
- Topical compositions of the present invention typically include or are incorporated into different types of vehicles and carriers.
- the topical composition of the present invention further comprises a topically acceptable carrier.
- the vehicle or carrier can be a pharmaceutically and/or dermatologically acceptable vehicle or carrier.
- Non-limiting examples of vehicles or carriers include water, glycerin, alcohol, oil, a silicon containing compound, a silicone compound, and wax. Variations and other appropriate vehicles will be apparent to the skilled artisan and are appropriate for use in the present invention.
- the concentrations and combinations of the compounds, ingredients, and agents can be selected in such a way that the combinations are chemically compatible and do not form complexes which precipitate from the finished product.
- a topical composition may contain a Ce -Cioo ester base which functions as an acceptable carrier for the one or more compounds of formula I.
- ester bases include:
- esters may be formed from the reaction between C1-C22 alkanoic acid with neopentyl alcohol, neopentyl glycol, 2- butyl-2-ethyl- 1,3-propanediol,
- 2, 2, 4- lrimethyl- 1,3-pentane diol trimethylol propane, pentaerythritol, di-trimethylol propane, di-pentaerythritol or pentaerythritol-trimethylol propane dimers.
- Examples include isostearyl neopentanoate, palmityl neopentanoate, tetraoctylpentaerythritol and diisopropyl neopentanoate.
- Amounts of this ester may suitably range from 1% to 90%, preferably from 20% to 75%, optimally from 30% to 50% by weight of the topical composition.
- the C12 -C40 fatty glyceride ester alkoxylate preferably includes 4 to 20 moles alkylene oxide per mole of glyceride.
- Preferred alkylene oxides are ethylene oxide and propylene oxide. Examples are PEG-6 caprylic/capric glyceride and PEG-8 caprylic/capric glyceride each of which are polyethylene glycol derivatives of a mixture of mono, di and triglycerides of caprylic and capric acids with a respective 6 and 8 moles of ethylene oxide. Amounts of this ester may suitably range from 1% to 90%, preferably from 5% to 50%, optimally from 10% to 20% by weight of the topical composition.
- polyglycerol Cs -C22 mono or di-fatty acid ester examples include polyglycerol-3 beeswax, polyglycerol-4 cocoate, poly glycerol- 10 decalinoleate, poly glycerol- 10 decaoleate, polyglycerol-7 decastearate, polyglycerol-2 diisostearate, polyglycerol-3 diisostearate, polyglycerol-7 diisostearate, polyglycerol-2 dioleate, polyglycerol-3 dioleate, polyglycerol-6 dioleate, poly glycerol- 10 dioleate, polyglycerol-3 distearate, polyglycerol-6 distearate, poly glycerol- 10 distearate, poly glycerol- 10 heptaoleate, poly glycerol- 10 heptastearate, polyglycerol-6 hexaoleate, polyglycerol-2
- polyglycerol-6 dioleate which is a diester of oleic acid and a glycerin polymer containing an average of 6 glycerin units. Amounts of this ester may range from 1% to 50%, preferably from 5% to 25%, optimally from 10% to 20% by weight of the topical composition.
- Non-limiting examples include cetyl octanoate, lauryl pentanoate, palmityl palmitoate, isostearyl decanoate, oleyl heptanoate and combinations thereof. Amounts of this material may range from 1% to 50%, preferably from 5% to 30%, optimally from 10% to 20% by weight of the topical composition.
- the ester base may range from about 30% to 95%, preferably from 40% to 80%, optimally from 50% to 70% by weight of the topical composition.
- the topical compositions may further contain a solubiliser in the form of a glycerol C8-C22 mono fatty acid ester.
- solubilisers include glycerol monoisostearate, glycerol monobehenate and glycerol monopalmitate.
- the solubiliser may comprise about 0.1% to 20%, preferably from 0.5% to 10%, optimally from 1% to 5%, by mass of the topical composition.
- the topical compositions may contain other carriers such as silicone oils.
- the silicone oils may be cyclic or linear polydimethylsiloxanes containing from 3 to 9, preferably from 4 to 5, silicon atoms, or polyalkyl siloxanes, polyalklyaryl siloxanes and polyether siloxane copolymers. Silicones may be present in amounts generally ranging from 1% to 50%, preferably from 2% to 25%, optimally between 10% and 20% by weight of the topical composition.
- the topical compositions may also include additional ingredients typically found in cosmetic and skin care formulations such as cosmetic ingredients and pharmaceutical active ingredients.
- topical compositions of the invention may include chalk, talc, fullers, earth, kaolin, starch, smectites clays, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, aluminum starch octenyl succinate.
- surfactants may be added including alkyl sulfates, such as Sodium Lauryl Sulfate, Sodium Laureth Sulfate, Sodium Coco-Sulfate and Sodium Trideceth Sulfate, betaines, such as cocobetaine, and carbohydrates, such as Lauryl Glucoside and Coco-Glucoside.
- Other ingredients are colouring agents, opacifiers and perfumes. Amounts of these adjunct materials may conveniently range anywhere from 0.001% up to 20% by weight of the composition.
- fragrance agents artificial and natural; e.g., gluconic acid, phenoxy ethanol, and triethanolamine
- dyes and color ingredients e.g., Blue 1, Blue 1 Lake, Red 40, titanium dioxide, D&C blue no. 4, D&C green no. 5, D&C orange no. 4, D&C red no. 17, D&C red no. 33, D&C violet no. 2, D&C yellow no. 10, and D&C yellow no.
- flavoring agents / aroma agents e.g., Stevia rebaudiana (sweetleaf) extract, and menthol
- adsorbents e.g., adsorbents, lubricants, solvents, moisturizers (including, e.g., emollients, humectants, film formers, occlusive agents, and agents that affect the natural moisturization mechanisms of the skin), water-repellants, UV absorbers and/or reflectors (physical and chemical absorbers such as para-aminobenzoic acid (“PABA”) and corresponding PABA derivatives, titanium dioxide, zinc oxide, etc.), essential oils, vitamins (e.g., A, B, C, D, E, and K), trace metals (e.g., zinc, calcium and selenium), anti -irritants (e.g., steroids and non-steroidal anti-inflammatories), botanical extracts (e.g., Aloe vera, chamomile, cucumber extract, Gink
- the topical compositions may also include fatty alcohols and fatty acids having from 10 to 20 carbon atoms. Especially preferred are such compounds as cetyl, myristyl, palmityl, isostearyl and stearyl alcohols and acids.
- the topical compositions may further include a-hydroxy carboxylic acids. Suitable examples include: a-hydroxyethanoic acid, a-hydroxypropanoic acid, a-hydroxyhexanoic acid, a- hydroxyoctanoic acid, a-hydroxydecanoic acid, a-hydroxydodecanoic acid, a- hydroxytetradecanoic acid, a-hydroxyhexadecanoic acid, a-hydroxyoctadecanoic acid, a- hydroxyeicosanoic acid, a-hydroxydocosanoic acid, a-hydroxyhexacosanoic acid, and a- hydroxyoctacosanoic acid.
- the a-hydroxy carboxylic acid may be in the acid form or in salt form.
- Typical salts are the alkalimetal, ammonium and Ci -C30 ammonium salts, for example the sodium, potassium, triethanolammonium and ammonium salts form.
- Typical salts are the alkalimetal, ammonium and C2 -C30 ammonium salts, for example the sodium, potassium, triethanolammonium and ammonium salts.
- the a -hydroxy carboxylic acid will generally be present in a range from 0.001% to 20%, preferably from 0.01% to 15%, optimally from 0.5% to 10% by weight of the topical composition.
- the topical composition may also include vitamins.
- Examples include sources or derivatives of vitamin C, such as ascorbyl palmitate, ascorbyl glucoside, magnesium ascorbyl phosphate, ascorbyl lysostearate, vitamin A palmitate (retinyl palmitate) and vitamin E linoleate (tocopheryl linoleate).
- sources or derivatives of vitamin C such as ascorbyl palmitate, ascorbyl glucoside, magnesium ascorbyl phosphate, ascorbyl lysostearate, vitamin A palmitate (retinyl palmitate) and vitamin E linoleate (tocopheryl linoleate).
- vitamin C such as ascorbyl palmitate, ascorbyl glucoside, magnesium ascorbyl phosphate, ascorbyl lysostearate, vitamin A palmitate (retinyl palmitate) and vitamin E linoleate (tocopheryl linoleate).
- Other esters of vitamin C, vitamin A and vitamin E may also be
- the topical compositions may also include typical emulsifiers.
- the emulsifiers may be nonionic, anionic, cationic or amphoteric in nature.
- suitable emulsifiers include polyoxypropylene-polyoxyethylene ethers of cetyl alcohols and glycerol monoisostearate.
- the emulsifiers may suitably range from 0.5% to 30%, preferably from 1% to 15%, optimally from 3% to 8% by weight of the topical composition.
- the topical compositions may also include thickeners.
- thickeners include cross-linked polyacrylate materials and gums such as xanthan, carrageenan, gelatine, karaya, pectin and locust beans gum.
- the thickener may be present in amounts from about 0.1% to 20% by weight, preferably from 0.5% to 10% by weight, of the topical composition.
- the topical compositions may also contain suitable preservatives.
- suitable preservatives include alkyl esters of p-hydroxybenzoic acid, phenoxyethanol, hydantoin derivatives, proprionate salts, and a variety of quaternary ammonium compounds.
- Preservatives will usually be employed in amounts ranging from 0.1% to 2% by weight of the topical composition.
- the topical composition may also include substances such as p-anisic acid, sodium anisate, levulinic acid, sodium levulinate, sodium hydroxide, caprylyl glycol, 1,2-hexanediol, pentylene glycol, glyceryl caprylate, glyceryl caprate, ethylhexylglycerin, Undecylenamidopropyl-trimonium Methosulfate, propylene glycol, phenylpropanol, phenethyl alcohol, methylpropanediol, Dipropylene Glycol, or a combination thereof.
- substances such as p-anisic acid, sodium anisate, levulinic acid, sodium levulinate, sodium hydroxide, caprylyl glycol, 1,2-hexanediol, pentylene glycol, glyceryl caprylate, glyceryl caprate, ethylhexylglycerin,
- the present invention relates to a method for increasing the ceramide content of the stratum corneum, the method comprising topically administering a cosmetic composition of the present invention onto skin of an individual.
- the present invention relates to a method of improving skin barrier function, the method comprising topically administering a cosmetic composition of the present invention onto skin of an individual. In some embodiments, the present invention relates to a method of increasing keratinocyte terminal differentiation in the epidermis, the method comprising topically administering a cosmetic composition of the present invention onto skin an individual.
- the present invention relates to a method of upregulating enzymes in the epidermis associated with epidermal ceramide synthesis, the method comprising topically administering a cosmetic composition of the present invention onto skin of a subject.
- the methods may in some embodiments be for improving skin complexion, improving skin radiance, improving skin tone, skin soothing, reducing premature skin ageing, wrinkle smoothing and/or supporting healthy look of skin.
- the present invention relates to a method for non- pharmacological management of a skin disease, such as aphotic dermatitis, or condition associated with an impaired skin barrier function, such as increased transepidermal water loss (TEWL), dry skin, rough skin, irritated skin, the method comprising topically administering a composition comprising one or more compounds of formula I, in particular at least one said compound that has lactosyl or glycosyl residue in the position X of formula I, onto a skin of an individual.
- a skin disease such as aphotic dermatitis
- an impaired skin barrier function such as increased transepidermal water loss (TEWL)
- TEWL transepidermal water loss
- the invention related to non-pharmacological intervention for mitigation of a skin condition or a skin disease in an individual who has, or who is susceptible to developing an impaired skin barrier function, the method comprising topically administering a composition comprising one or more compounds of formula I, in particular at least one said compound that has lactosyl or glycosyl residue in the position X of formula I, onto a skin of said individual.
- the individual who is susceptible to an impaired skin barrier function according to the invention is an individual has either heredity of impaired skin barrier function, or been exposed to hazardous envinromental factors.
- the relevant hazardous environmental factors include, but not limited to, climatic conditions, such as UV light or chemical pollutants, such as polycyclic aromatic pollutants (PAH), particulate matter PM2.5, blue light, ozone or cigarette smoke.
- climatic conditions such as UV light or chemical pollutants, such as polycyclic aromatic pollutants (PAH), particulate matter PM2.5, blue light, ozone or cigarette smoke.
- PAH polycyclic aromatic pollutants
- the invention in general relates to an individual who is a mammal, e.g. a domestic animal, like a dog or cat, or a human individual.
- the individual is a human.
- the human individual is an adult individual, i.e. a human of 20+ years old; in other preferred embodiments, the human individual may be a child or a teenager.
- the later may be preferred, e.g., when compositions of the invention are intended for prophylactic treatment, such as non-pharmacological intervention for mitigation of a skin condition or a skin disease in an individual who has, or who is susceptible to developing an impaired skin barrier function.
- glucosyl ceramide NS on the skin leads to an upregulation of ATP synthase subunit g, (mitochondrial), of ATP synthase subunit delta (mitochondrial), of cytochrome c oxidase subunit 6C, of NADH dehydrogenase [ubiquinone] iron-sulfur protein 2 (mitochondrial), of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8, of ATP-dependent zinc metallopro tease YME1L1, of NAD-dependent malic enzyme (mitochondrial) and of phosphomevalonate kinase.
- lactosyl ceramide NS on the skin leads to an upregulation of ATP synthase subunit g, (mitochondrial), of ATP synthase subunit delta (mitochondrial), of cytochrome c oxidase subunit 6C, of cytochrome c oxidase subunit 2, of cytochrome c oxidase subunit NDUFA4, of cytochrome b-cl complex subunit 9, of ATP-dependent zinc metalloprotease YME1L1, of NAD-dependent malic enzyme (mitochondrial) and of phosphomevalonate kinase.
- ATP synthase subunit g mitochondrial
- ATP synthase subunit delta mitochondrial
- cytochrome c oxidase subunit 6C of cytochrome c oxidase subunit 2C
- cytochrome c oxidase subunit 2 of cytochrome c oxid
- ATP is a versatile biochemical form of energy used to fuel metabolic processes. ATP is generated by the respiratory chain. During age and stress energy production is decreased and metabolism slowed down. Repair mechanisms are weakend and damage is accelerated. Activating the respiratory chain and therefore ATP generation keeps the metabolism high and provides energy for repair mechanisms, cells stay healthy & functional resulting in a healthy skin with a radiant complexion. Furthermore, an activated metabolism supports skin regeneration and helps to fight against signs of ageing.
- ceramide NP ceramide NP
- ceramide NG glucosyl ceramide
- lactosyl ceramide or compositions comprising thereof may also be used for boosting energy of skin cells according to the invention.
- Boosting energy of the skin cells refers to an improvement of overall metabolism and ATP-production and may also be referred to as skin vitalisation or skin energizing.
- skin vitalisation or skin energizing.
- Topical composition comprising one or more compounds of formula I
- X is hydrogen or a glycosyl moiety, the carbon-carbon bond noted - is a double or a single bond,
- R 1 is an alkyl chain having 10 - 20 carbon atoms
- R 2 is hydrogen or a substituted or unsubstituted acyl having 16-34 carbon atoms
- R 3 is hydrogen when the carbon-carbon bond noted - is a double or a single bond, and R 3 is -OH when the carbon-carbon bond noted - is a single bond,
- R 4 is hydrogen when the carbon-carbon bond noted - is a double or a single bond, and R 4 is hydrogen or -OH when the carbon-carbon bond noted - is a double bond, said composition is characterized in that at least one of the one or more compounds of formula I has a lactosyl moiety or a glucosyl moiety in the position X.
- Topical composition according to embodiment 1 or 2 wherein for one or more of the compounds of formula I, the stereochemical configuration is (2S,3R,4E) and the carbon-carbon bond noted - is a double bond.
- Topical composition according to embodiment 1 or 2 wherein for one or more of the compounds of I, the stereochemical configuration is (2S,3S,4R) or (2S,3S), and the carbon-carbon bond noted - is a single bond.
- Topical composition according to any one of embodiments 1 to 4, wherein for one or more of the compounds of formula I, R 1 is -C12H25 and/or R 2 is selected from hexadecanoyl, 2-hydroxyhexadecanoyl, octadecanoyl, 2-hydroxyoctadecanoyl, eicosanoyl, 2-hydroxyeicosanoyl, lignoceroyl, 2-hydroxytetracosanoyl, 30- (linoley loxy ) -triacontanoy 1.
- a topical cosmetic composition comprising a composition according to any one of embodiments 1-12, for use in cosmetic treatment of skin of an individual, wherein said treatment improves the visual appearance of skin of said individual.
- lactosyl ceramide for increasing the ceramide content of the stratum comeum, increasing keratinocyte terminal differentiation in the epidermis, upregulating enzymes in the epidermis associated with epidermal ceramide synthesis, and/or improving skin barrier function in skin of an individual.
- ceramide NP for increasing the ceramide content of the stratum comeum, increasing keratinocyte terminal differentiation in the epidermis, upregulating enzymes in the epidermis associated with epidermal ceramide synthesis, and/or improving skin barrier function in skin of an individual.
- ceramide NG for increasing the ceramide content of the stratum comeum, increasing keratinocyte terminal differentiation in the epidermis, upregulating enzymes in the epidermis associated with epidermal ceramide synthesis, and/or improving skin barrier function in skin of an individual.
- glucosyl ceramide for increasing the ceramide content of the stratum comeum, upregulating enzymes in the epidermis associated with epidermal ceramide synthesis, and/or improving skin barrier function in skin of an individual.
- ceramide NS for increasing keratinocyte terminal differentiation in the epidermis and/or improving skin barrier function in skin of an individual.
- a topical pharmaceutical composition comprising a composition according to embodiment 21, further comprising one or more compounds that are structurally different from a compound of formula I, and/or pharmaceutically active for treating of a skin disease or a pathological skin condition.
- Method for non-pharmacological management of a skin condition associated with an impaired skin barrier function such as increased transepidermal water loss (TEWL), dry skin, rough skin, irritated skin, the method comprising topically administering a composition of any one of embodiments 1 to 13 onto a skin of an individual.
- Method for non-pharmacological intervention for mitigation of a skin condition or a skin disease in an individual who has, or who is susceptible to developing an impaired skin barrier function the method comprising topically administering a composition of any one of embodiments 1 to 13 onto a skin of said individual. 26. Method according to embodiment 25, wherein the individual who is susceptible to an impaired skin barrier function has heredity of impaired skin barrier function, or been exposed to hazardous envinromental factors.
- climatic conditions such as UV light or chemical pollutants, such as polycyclic aromatic pollutants (PAH), particulate matter PM2.5, blue light, ozone or cigarette smoke.
- PAH polycyclic aromatic pollutants
- Example 1 Topical compositions comprising ceramide blends
- Example 2 Topical compositions comprising ceramide blends
- Example 3 Human epidermal keratinocytes are obtained from a commercial vendor.
- the cells are isolated from juvenile foreskin or from adult normal human tissue collected from various sites that include face, breast, abdomen, and thigh.
- the cells are cultivated in a T25 flask using a commercial keratinocyte Growth Medium which is a serum-free medium and optimized for the in vitro cultivation of epidermal keratinocytes without feeder cells.
- a commercial growth supplement and calcium is added to a final concentration of 1.2mM to induce differentiation.
- the cells Upon reaching cell confluence, the cells are treated with either 200 ppm glucosylceramide or 200 ppm lactosylceramide, each dissolved in dimethyl sulfoxide (DMSO) for 1 week.
- DMSO dimethyl sulfoxide
- the cells are homogenised with 2mL chloroform: methanol (2:1), and transferred to a vial containing Phosphate Buffered Saline (PBS). The homogeniser is rinsed twice with solvent and all rinses are together. The organic phase is evaporated to dryness.
- PBS Phosphate Buffered Saline
- Ceramide levels produced by the keratinocytes are measured by a modified high-performance thin layer chromatography (HPTLC) method.
- HPTLC high-performance thin layer chromatography
- the dried residue is dissolved in 200pL chloroforrmmethanol (2:1).
- Samples of 80pl and 20pL are then subjected to a HPTLC protocol in which the HPTLC plates are developed using a sequential development system: (1) dichloromethane:ethylacetate: acetone (80:16:4) to 85mm, (2) chloroforrmmethanohacetone (76:16:8) to 80mm, (3) hexane:chloroform:acetic acid: acetone: methanol (6:80:0.1:10:4) to 85mm.
- the plates are stained with 3% copper acetate in 8% phosphoric acid and charred at 160°C for the quantitation of ceramides. Quantification is performed against known quantities of Ceramide NP by laser scanning densitometry. Each plate is scanned at 425nm and quantified using WinCATS software.
- Gene expression is determined by isolating RNA samples from the keratinocytes using a Qiagen RNeasy kit with DNase I digestion. Reverse transcription is performed using a high- capacity cDNA kit. cDNA samples of 40ng are used for qPCR. Taqman gene expression assay is purchased commercially, and the qPCR reaction is performed using a fast amplifier. Data are normalized by reference genes, either polymerase (RNA) II polypeptide A (POLR2A) and ribosomal protein large, PO (RPLPO) of which expression does not change by the treatment. Relative gene expression is calculated by comparative CT method.
- RNA polymerase II polypeptide A
- RPLPO ribosomal protein large, PO
- GABA b-glucocerebrosidase
- Total ceramides in keratinocytes treated glucosylceramide or lactosylceramide are elevated compared to untreated keratinocytes.
- the differentiation marker genes, involucrin and transglutaminase- 1 increase in expression. This response is also observed in additional genes of keratinocyte differentiation as SPRR1 and SPRR2.
- the keratinocytes treated with glucosylceramide or lactosylceramide display reduced gene expression of inflammatory cytokines such as IL8 and TNF.
- Example 4 Characterisation of effects of (glycosylated) ceramides and (glvco)sphingolipids as cosmetic active ingredients
- RHE Reconstructed Human Epidermis
- This system mimics the in vivo 3D structure of epidermal tissue as well as the conditions and processes that occur in normal epidermis.
- RHE were cultured using the medium provided by the manufacturer until analysis.
- RHE were maintained in survival for 24 hours, before RHE were topically treated with lipid in a base emulsion for 24h.
- 3 RHE were treated with base emulsion alone and 3 more remained untreated as a control batch (Ctrl).
- RHE were incubated under classical cell culture conditions (37°C, 5% C02).
- Bioinformatics and statistical analysis Proteomic analysis returned a mean total of 34961 high-quality peptides corresponding to a mean 2422 identifiable and quantifiable RHE proteins among conditions. A summary of proteins differentially expressed within conditions is provided in Annexe 3. Proteins with a p-value ⁇ 0.05 in at least one of the concentrations tested for a lipid were considered significant and used for pairwise comparisons. Relevant proteins were classified by their biological processes and associated pathways using the publicly available gene ontology (GO) database provided by the Gene Ontology Consortium and Reactome. Interactome analysis was performed using Cytoscape combined with STRING.
- GO gene ontology
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)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Birds (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne une composition topique comprenant un ou plusieurs composés de formule I, X représentant un atome d'hydrogène ou une fraction glycosyle, la liaison carbone-carbone notée étant une liaison double ou une liaison simple, R1 étant une chaîne alkyle ayant de 10 à 20 atomes de carbone, R2 représentant un atome d'hydrogène ou un groupe acyle substitué ou non substitué ayant 16 à 34 atomes de carbone, R3 représentant de l'hydrogène lorsque la liaison carbone-carbone notée est une liaison double ou une liaison simple et R3 représentant -OH lorsque la liaison carbone-carbone notée est une liaison simple, R4 représentant de l'hydrogène lorsque la liaison carbone-carbone notée est une liaison double ou une liaison simple et R4 représentant de l'hydrogène ou -OH lorsque la liaison carbone-carbone notée est une double liaison, ladite composition étant caractérisée en ce qu'au moins l'un parmi le ou les composés de formule I a une fraction lactosyle ou une fraction glucosyle dans la position X.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH4702021 | 2021-04-30 | ||
PCT/PT2022/050018 WO2022231448A1 (fr) | 2021-04-30 | 2022-04-29 | Compositions topiques comprenant des (glyco)sphingolipides et/ou des (glyco)céramides |
Publications (1)
Publication Number | Publication Date |
---|---|
EP4329718A1 true EP4329718A1 (fr) | 2024-03-06 |
Family
ID=89048534
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP22726199.7A Pending EP4329718A1 (fr) | 2021-04-30 | 2022-04-29 | Compositions topiques comprenant des (glyco)sphingolipides et/ou des (glyco)céramides |
Country Status (3)
Country | Link |
---|---|
US (1) | US20240238186A1 (fr) |
EP (1) | EP4329718A1 (fr) |
CN (1) | CN117222396A (fr) |
-
2022
- 2022-04-29 CN CN202280031950.3A patent/CN117222396A/zh active Pending
- 2022-04-29 US US18/557,661 patent/US20240238186A1/en active Pending
- 2022-04-29 EP EP22726199.7A patent/EP4329718A1/fr active Pending
Also Published As
Publication number | Publication date |
---|---|
US20240238186A1 (en) | 2024-07-18 |
CN117222396A (zh) | 2023-12-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2907495C (fr) | Compositions d'antioxydants et procedes d'utilisation | |
KR101695002B1 (ko) | 프로판노이드 유도체를 함유하는 피부 외용제 조성물 | |
JP5734648B2 (ja) | 高麗人参の実抽出物を含有する皮膚外用剤組成物 | |
US8709511B2 (en) | External preparation composition for skin comprising ginseng flower or ginseng seed extracts | |
KR101199672B1 (ko) | 방향성 피부활성 성분을 사용하여 피부를 치료하는 방법 | |
JP5686365B2 (ja) | コラーゲン産生促進剤、光老化防止剤、保湿機能改善剤および皮膚用剤組成物 | |
KR101517950B1 (ko) | 철갑상어로부터 수득한 점액을 함유하는 화장료 조성물 | |
KR100519638B1 (ko) | 지질 장벽 합성을 강화시키는 조성물 및 그 방법 | |
KR101707522B1 (ko) | 인삼 꽃 추출물을 함유하는 피부 외용제 조성물 | |
KR20090130801A (ko) | 인삼씨 추출물을 함유하는 피부 외용제 조성물 | |
JP2004091376A (ja) | 表皮角化正常化剤及びこれを含有する皮膚外用剤 | |
WO2022231448A1 (fr) | Compositions topiques comprenant des (glyco)sphingolipides et/ou des (glyco)céramides | |
KR101503158B1 (ko) | 피부 주름 개선 및 탄력 증진용 화장료 조성물 | |
JP2004538299A (ja) | クレアチニンおよび/またはクレアチニン誘導体を化粧用および皮膚科学用調剤で用いる使用 | |
US20240238186A1 (en) | Topical Compositions Comprising (Glyco)Sphingolipids and/or (Glyco)Ceramides | |
CN115209887A (zh) | Ppar激动剂复合物及其使用方法 | |
WO2023209655A1 (fr) | Composition améliorant l'énergie des cellules cutanées | |
US20210015847A1 (en) | Skin preparation composition for external use containing complex hyaluronic acid | |
JP4488933B2 (ja) | シワ改善剤及び皮膚外用組成物 | |
JP2002128702A (ja) | 局所活性成分の効力のモノ−アシル−(リゾ)−グリセロリン脂質による増強方法およびその用途 | |
EP1080719A2 (fr) | Méthodes pour la potentialisation de l'efficacité d'actifs topiques par les mono-acyl-(lyso)-glycerophospholipides | |
WO2024028834A1 (fr) | Réduction des signes du vieillissement de la peau | |
KR101754556B1 (ko) | 수베르산 또는 이의 염을 유효성분으로 함유하는 피부보습 개선 또는 피부탄력 증진 효과를 갖는 조성물 | |
KR20240019216A (ko) | 개선된 세포 투과성 핵 수송 억제제를 포함하는 피부 노화 방지 또는 피부 주름 개선용 화장료 조성물 | |
TW202404562A (zh) | 用於治療皮膚色素沉著病症之組成物及方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: UNKNOWN |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE |
|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE |
|
17P | Request for examination filed |
Effective date: 20231128 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |