JP6815782B2 - α-SMA production inhibitor - Google Patents
α-SMA production inhibitor Download PDFInfo
- Publication number
- JP6815782B2 JP6815782B2 JP2016149624A JP2016149624A JP6815782B2 JP 6815782 B2 JP6815782 B2 JP 6815782B2 JP 2016149624 A JP2016149624 A JP 2016149624A JP 2016149624 A JP2016149624 A JP 2016149624A JP 6815782 B2 JP6815782 B2 JP 6815782B2
- Authority
- JP
- Japan
- Prior art keywords
- sma
- sulfated
- production inhibitor
- acid
- acetyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 51
- 239000003112 inhibitor Substances 0.000 title claims description 36
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims description 25
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims description 25
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 13
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 13
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 10
- 150000002337 glycosamines Chemical class 0.000 claims description 10
- 239000000470 constituent Substances 0.000 claims description 9
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 claims description 7
- 230000014509 gene expression Effects 0.000 description 21
- -1 alkali metal salts Chemical class 0.000 description 18
- 210000003491 skin Anatomy 0.000 description 18
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 15
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 11
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 11
- 229920001284 acidic polysaccharide Polymers 0.000 description 9
- 150000004805 acidic polysaccharides Chemical group 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 231100000241 scar Toxicity 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 230000029663 wound healing Effects 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 101500025614 Homo sapiens Transforming growth factor beta-1 Proteins 0.000 description 6
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 239000006210 lotion Substances 0.000 description 6
- 208000032544 Cicatrix Diseases 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 229920002971 Heparan sulfate Polymers 0.000 description 5
- 206010072170 Skin wound Diseases 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 230000001969 hypertrophic effect Effects 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000037387 scars Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 5
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 208000002260 Keloid Diseases 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 208000001132 Osteoporosis Diseases 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 210000004207 dermis Anatomy 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 210000001117 keloid Anatomy 0.000 description 4
- AEMOLEFTQBMNLQ-CLQWQSTFSA-N l-iduronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@@H](O)[C@@H]1O AEMOLEFTQBMNLQ-CLQWQSTFSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 210000000651 myofibroblast Anatomy 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000004166 Lanolin Substances 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical group N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229930182830 galactose Natural products 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 235000019388 lanolin Nutrition 0.000 description 3
- 229940039717 lanolin Drugs 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 2
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 2
- ASKIVFGGGGIGKH-UHFFFAOYSA-N 2,3-dihydroxypropyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OCC(O)CO ASKIVFGGGGIGKH-UHFFFAOYSA-N 0.000 description 2
- FLPJVCMIKUWSDR-UHFFFAOYSA-N 2-(4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1 FLPJVCMIKUWSDR-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
- 241000723346 Cinnamomum camphora Species 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 description 2
- 229930008380 camphor Natural products 0.000 description 2
- 229960000846 camphor Drugs 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 229940074979 cetyl palmitate Drugs 0.000 description 2
- 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 2
- NEHNMFOYXAPHSD-UHFFFAOYSA-N citronellal Chemical compound O=CCC(C)CCC=C(C)C NEHNMFOYXAPHSD-UHFFFAOYSA-N 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- PXDJXZJSCPSGGI-UHFFFAOYSA-N hexadecanoic acid hexadecyl ester Natural products CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 2
- 229940075495 isopropyl palmitate Drugs 0.000 description 2
- 229940041616 menthol Drugs 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000012723 sample buffer Substances 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229940083542 sodium Drugs 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 1
- CRDAMVZIKSXKFV-FBXUGWQNSA-N (2-cis,6-cis)-farnesol Chemical compound CC(C)=CCC\C(C)=C/CC\C(C)=C/CO CRDAMVZIKSXKFV-FBXUGWQNSA-N 0.000 description 1
- 239000000260 (2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol Substances 0.000 description 1
- QYIXCDOBOSTCEI-QCYZZNICSA-N (5alpha)-cholestan-3beta-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-QCYZZNICSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- UYZQWKKNVBJVOF-UHFFFAOYSA-N 1-decoxytetradecane Chemical compound CCCCCCCCCCCCCCOCCCCCCCCCC UYZQWKKNVBJVOF-UHFFFAOYSA-N 0.000 description 1
- JPPRXACMNPYJNK-UHFFFAOYSA-N 1-docosoxydocosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCCCCCC JPPRXACMNPYJNK-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- JWKSQNWLEIABLH-UHFFFAOYSA-N 1-octan-2-yloxydodecane Chemical compound CCCCCCCCCCCCOC(C)CCCCCC JWKSQNWLEIABLH-UHFFFAOYSA-N 0.000 description 1
- LVOGXJMCDAOKSQ-UHFFFAOYSA-N 10-oxo-10-propan-2-yloxydecanoic acid Chemical compound CC(C)OC(=O)CCCCCCCCC(O)=O LVOGXJMCDAOKSQ-UHFFFAOYSA-N 0.000 description 1
- GQQNRZHWHWHOLI-UHFFFAOYSA-N 11-(2-decyltetradecoxymethyl)tricosane Chemical compound CCCCCCCCCCCCC(CCCCCCCCCC)COCC(CCCCCCCCCC)CCCCCCCCCCCC GQQNRZHWHWHOLI-UHFFFAOYSA-N 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
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- RRZWKUGIZRDCPB-UHFFFAOYSA-N 2,3-dihydroxypropyl hexanoate Chemical compound CCCCCC(=O)OCC(O)CO RRZWKUGIZRDCPB-UHFFFAOYSA-N 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- ZVUNTIMPQCQCAQ-UHFFFAOYSA-N 2-dodecanoyloxyethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOC(=O)CCCCCCCCCCC ZVUNTIMPQCQCAQ-UHFFFAOYSA-N 0.000 description 1
- IKVCSHRLYCDSFD-UHFFFAOYSA-N 2-hexadecanoyloxyethyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCCOC(=O)CCCCCCCCCCCCCCC IKVCSHRLYCDSFD-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 description 1
- MOMKYJPSVWEWPM-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-methylphenyl)-1,3-thiazole Chemical compound C1=CC(C)=CC=C1C1=NC(CCl)=CS1 MOMKYJPSVWEWPM-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- TZZAKSLHHIJRLL-UHFFFAOYSA-N 4-hydroxy-3-methoxybenzamide Chemical compound COC1=CC(C(N)=O)=CC=C1O TZZAKSLHHIJRLL-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000238366 Cephalopoda Species 0.000 description 1
- 229920002567 Chondroitin Polymers 0.000 description 1
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 235000005956 Cosmos caudatus Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 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
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- FPVVYTCTZKCSOJ-UHFFFAOYSA-N Ethylene glycol distearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOC(=O)CCCCCCCCCCCCCCCCC FPVVYTCTZKCSOJ-UHFFFAOYSA-N 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 239000004471 Glycine Substances 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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229920000288 Keratan sulfate Polymers 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 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
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- KCLANYCVBBTKTO-UHFFFAOYSA-N Proparacaine Chemical compound CCCOC1=CC=C(C(=O)OCCN(CC)CC)C=C1N KCLANYCVBBTKTO-UHFFFAOYSA-N 0.000 description 1
- 235000019484 Rapeseed oil Nutrition 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- SLINHMUFWFWBMU-UHFFFAOYSA-N Triisopropanolamine Chemical compound CC(O)CN(CC(C)O)CC(C)O SLINHMUFWFWBMU-UHFFFAOYSA-N 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
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- NCHJGQKLPRTMAO-XWVZOOPGSA-N [(2R)-2-[(2R,3R,4S)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NCHJGQKLPRTMAO-XWVZOOPGSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- QYIXCDOBOSTCEI-UHFFFAOYSA-N alpha-cholestanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 QYIXCDOBOSTCEI-UHFFFAOYSA-N 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 229950004580 benzyl nicotinate Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 1
- 229940116229 borneol Drugs 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000010495 camellia oil Substances 0.000 description 1
- 239000004204 candelilla wax Substances 0.000 description 1
- 235000013868 candelilla wax Nutrition 0.000 description 1
- 229940073532 candelilla wax Drugs 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 229940007061 capsicum extract Drugs 0.000 description 1
- 239000001943 capsicum frutescens fruit extract Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 description 1
- 229940074393 chlorogenic acid Drugs 0.000 description 1
- 235000001368 chlorogenic acid Nutrition 0.000 description 1
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 229950001002 cianidanol Drugs 0.000 description 1
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 1
- 229940043350 citral Drugs 0.000 description 1
- 229930003633 citronellal Natural products 0.000 description 1
- 235000000983 citronellal Nutrition 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
- 150000002016 disaccharides Chemical group 0.000 description 1
- 229950010030 dl-alanine Drugs 0.000 description 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 1
- 229960000735 docosanol Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000010696 ester oil Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 description 1
- 229940031016 ethyl linoleate Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229940043259 farnesol Drugs 0.000 description 1
- 229930002886 farnesol Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 229940074391 gallic acid Drugs 0.000 description 1
- 235000004515 gallic acid Nutrition 0.000 description 1
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 229940100608 glycol distearate Drugs 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 239000001685 glycyrrhizic acid Substances 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- IUJAMGNYPWYUPM-UHFFFAOYSA-N hentriacontane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC IUJAMGNYPWYUPM-UHFFFAOYSA-N 0.000 description 1
- XJNUECKWDBNFJV-UHFFFAOYSA-N hexadecyl 2-ethylhexanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)C(CC)CCCC XJNUECKWDBNFJV-UHFFFAOYSA-N 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- FMMOOAYVCKXGMF-UHFFFAOYSA-N linoleic acid ethyl ester Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC FMMOOAYVCKXGMF-UHFFFAOYSA-N 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 229960002373 loxoprofen Drugs 0.000 description 1
- WORCCYVLMMTGFR-UHFFFAOYSA-M loxoprofen sodium Chemical compound [Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 WORCCYVLMMTGFR-UHFFFAOYSA-M 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 150000002696 manganese Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- CTIQLGJVGNGFEW-UHFFFAOYSA-L naphthol yellow S Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C([O-])=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 CTIQLGJVGNGFEW-UHFFFAOYSA-L 0.000 description 1
- 125000001400 nonyl 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])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960003981 proparacaine Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940092258 rosemary extract Drugs 0.000 description 1
- 235000020748 rosemary extract Nutrition 0.000 description 1
- 239000001233 rosmarinus officinalis l. extract Substances 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 235000019983 sodium metaphosphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229940044609 sulfur dioxide Drugs 0.000 description 1
- 235000010269 sulphur dioxide Nutrition 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- CRDAMVZIKSXKFV-UHFFFAOYSA-N trans-Farnesol Natural products CC(C)=CCCC(C)=CCCC(C)=CCO CRDAMVZIKSXKFV-UHFFFAOYSA-N 0.000 description 1
- HVUCRESARJLKJG-UHFFFAOYSA-K trisodium 1-hexadecoxyhexadecane phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O.CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC HVUCRESARJLKJG-UHFFFAOYSA-K 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、α−SMA産生抑制剤に関する。より具体的には、本発明は、α−SMAの産生を抑制することにより、α−SMAの過剰な発現等によってもたらされる症状や疾患を改善できるα−SMA産生抑制剤に関する。 The present invention relates to an α-SMA production inhibitor. More specifically, the present invention relates to an α-SMA production inhibitor that can improve symptoms and diseases caused by excessive expression of α-SMA by suppressing the production of α-SMA.
α−SMA(α−平滑筋アクチン)は、筋線維芽細胞において多く発現しているタンパク質であり、α−SMAを発現することによって筋線維芽細胞は収縮能を獲得することが知られている。創傷治癒過程では、線維芽細胞が、α−SMAを発現する強い収縮能をもつ筋線維芽細胞に変化して、肉芽組織を収縮させ、傷口を小さくする役割を果たし、α−SMAの発現促進が創傷治癒に寄与することが知られている。また、α−SMAを発現する筋線維芽細胞は、真皮の強度や皮膚のハリに重要な役割を果たしていることも知られている。そこで、従来、α−SMAの産生を促進する物質についてスクリーニングされており、種々のα−SMA産生促進剤が報告されている(例えば、特許文献1及び2参照)。 α-SMA (α-smooth muscle actin) is a protein that is highly expressed in myofibroblasts, and it is known that myofibroblasts acquire contractile ability by expressing α-SMA. .. In the wound healing process, fibroblasts are transformed into myofibroblasts with strong contractile ability that express α-SMA, play a role in contracting granulation tissue and reducing wounds, and promote the expression of α-SMA. Is known to contribute to wound healing. It is also known that myofibroblasts expressing α-SMA play an important role in the strength of the dermis and the firmness of the skin. Therefore, conventionally, substances that promote the production of α-SMA have been screened, and various α-SMA production promoters have been reported (see, for example, Patent Documents 1 and 2).
一方、肥厚性瘢痕やケロイド等の皮膚創傷治癒異常では、筋繊維芽様細胞の出現が認められ、当該細胞のα−SMAの過剰な発現が悪影響を示すことが知られている。また、α−SMAは、腫瘍細胞の転移や骨粗鬆症にも関与していることが報告されている(特許文献3参照)。また、PDGF(血小板由来成長因子)は、α−SMAを阻害する作用があり、α−SMA阻害剤として使用できることも知られている(特許文献3参照)。しかしながら、従来、細胞におけるα−SMAの産生自体を抑制する物質については見出されていない。 On the other hand, in abnormal skin wound healing such as hypertrophic scars and keloids, the appearance of myofibroblast-like cells is observed, and it is known that excessive expression of α-SMA of the cells exerts an adverse effect. It has also been reported that α-SMA is also involved in tumor cell metastasis and osteoporosis (see Patent Document 3). It is also known that PDGF (platelet-derived growth factor) has an action of inhibiting α-SMA and can be used as an α-SMA inhibitor (see Patent Document 3). However, conventionally, no substance has been found that suppresses the production of α-SMA in cells.
そのため、α−SMAの産生を抑制できる物質を見出すことができれば、新たな手法で、肥厚性瘢痕やケロイド等の皮膚創傷治癒異常の症状を改善でき、更に腫瘍細胞の転移や骨粗鬆症等にも有効になると期待できるが、前述するように、従来、このような物質は見出されていないのが現状である。 Therefore, if a substance that can suppress the production of α-SMA can be found, it is possible to improve the symptoms of abnormal skin wound healing such as hypertrophic scars and keloids, and it is also effective for tumor cell metastasis and osteoporosis. However, as mentioned above, the current situation is that such a substance has not been found in the past.
本発明の目的は、α−SMAの産生を抑制できる物質を見出し、α−SMA産生抑制剤を提供することである。 An object of the present invention is to find a substance capable of suppressing the production of α-SMA and to provide an agent for suppressing the production of α-SMA.
本発明者等は、前記課題を解決すべく鋭意検討を行ったところ、硫酸化グリコサミノグリカンには、α−SMAの産生を抑制する作用があり、α−SMA産生抑制剤として使用できることを見出した。本発明は、かかる知見に基づいてさらに検討を重ねることにより完成したものである。
即ち、本発明は、下記に掲げる態様の発明を提供する。
項1. 硫酸化グリコサミノグリカン及び/又はその塩を含有する、α−SMA産生抑制剤。
項2. 硫酸化グリコサミノグリカン及び/又はその塩を構成するアミノ糖が、第4位及び/又は第6位の水酸基が硫酸化されているN−アセチル−D−ガラクトサミンである、項1に記載のα−SMA産生抑制剤。
項3. 前記アミノ糖は、第4位及び第6位の水酸基が硫酸化されているN−アセチル−D−ガラクトサミンである、項2に記載のα−SMA産生抑制剤。
項4. 前記硫酸化グリコサミノグリカン及び/又はその塩の構成糖としてD−グルクロン酸が含まれる、項1〜3のいずれかに記載のα−SMA産生抑制剤。
項5. 前記硫酸化グリコサミノグリカン及び/又はその塩が、コンドロイチン硫酸A、コンドロイチン硫酸C、コンドロイチン硫酸E、ヘパラン硫酸、及びそれらの塩よりなる群から選択される少なくとも1種である、項1〜4のいずれかに記載のα−SMA産生抑制剤。
項6. 前記硫酸化グリコサミノグリカン及び/又はその塩が、コンドロイチン硫酸E及び/又はその塩である、項1〜4のいずれかに記載のα−SMA産生抑制剤。
項7. 皮膚外用剤である、項1〜6のいずれかに記載のα−SMA産生抑制剤。
As a result of diligent studies to solve the above problems, the present inventors have found that sulfated glycosaminoglycan has an effect of suppressing the production of α-SMA and can be used as an α-SMA production inhibitor. I found it. The present invention has been completed by further studies based on such findings.
That is, the present invention provides the inventions of the following aspects.
Item 1. An α-SMA production inhibitor containing a sulfated glycosaminoglycan and / or a salt thereof.
Item 2. Item 2. The item 1 wherein the amino sugar constituting the sulfated glycosaminoglycan and / or a salt thereof is N-acetyl-D-galactosamine in which the hydroxyl groups at the 4- and / or 6-positions are sulfated. α-SMA production inhibitor.
Item 3. Item 2. The α-SMA production inhibitor according to Item 2, wherein the amino sugar is N-acetyl-D-galactosamine in which the hydroxyl groups at the 4- and 6-positions are sulfated.
Item 4. Item 3. The α-SMA production inhibitor according to any one of Items 1 to 3, wherein D-glucuronic acid is contained as a constituent sugar of the sulfated glycosaminoglycan and / or a salt thereof.
Item 5. Item 1 to 4, wherein the sulfated glycosaminoglycan and / or a salt thereof is at least one selected from the group consisting of chondroitin sulfate A, chondroitin sulfate C, chondroitin sulfate E, heparan sulfate, and salts thereof. The α-SMA production inhibitor according to any one of.
Item 6. Item 4. The α-SMA production inhibitor according to any one of Items 1 to 4, wherein the sulfated glycosaminoglycan and / or a salt thereof is chondroitin sulfate E and / or a salt thereof.
Item 7. Item 2. The α-SMA production inhibitor according to any one of Items 1 to 6, which is an external preparation for skin.
本発明のα−SMA産生抑制剤によれば、α−SMAの発現を抑制できるので、α−SMAの過剰発現に起因して生じる症状や疾患、α−SMAが関与している症状や疾患や症状等の予防又は治療に有効である。 According to the α-SMA production inhibitor of the present invention, the expression of α-SMA can be suppressed, so that the symptoms and diseases caused by the overexpression of α-SMA, the symptoms and diseases associated with α-SMA, and the like. It is effective for prevention or treatment of symptoms.
本発明のα−SMA産生抑制剤は、硫酸化グリコサミノグリカン及び/又はその塩を含有することを特徴とする。以下、本発明のα−SMA産生抑制剤について詳述する。 The α-SMA production inhibitor of the present invention is characterized by containing a sulfated glycosaminoglycan and / or a salt thereof. Hereinafter, the α-SMA production inhibitor of the present invention will be described in detail.
[硫酸化グリコサミノグリカン及び/又はその塩]
本発明のα−SMA産生抑制剤では、α−SMAの産生を抑制させるための有効成分として、硫酸化グリコサミノグリカン及び/又はその塩を含有する。
[Sulfated glycosaminoglycans and / or salts thereof]
The α-SMA production inhibitor of the present invention contains sulfated glycosaminoglycan and / or a salt thereof as an active ingredient for suppressing the production of α-SMA.
硫酸化グリコサミノグリカンとは、ウロン酸又はガラクトースがアミノ糖にβ1−3結合、β1−4結合、又はα1−4結合でグリコシド結合した二糖単位(以下、「基本構成単位」と表記することがある)の繰り返し構造を有し、当該基本構成単位においてグリコシド結合に関与していない水酸基及び/又はアミノ基が部分的に硫酸化されている酸性多糖である。硫酸化グリコサミノグリカンは、通常は、枝分かれしていない直鎖状の骨格を有している。 Sulfated glycosaminoglycan is a disaccharide unit in which uronic acid or galactose is glycosidic-bonded to an amino sugar by β1-3 bond, β1-4 bond, or α1-4 bond (hereinafter referred to as “basic constituent unit”). It is an acidic polysaccharide having a repeating structure (which may be) and in which hydroxyl groups and / or amino groups that are not involved in glycosidic bonds in the basic structural unit are partially sulfated. Sulfated glycosaminoglycans usually have an unbranched linear skeleton.
硫酸化グリコサミノグリカンの基本構成単位を構成するウロン酸は、具体的には、L−イズロン酸又はD−グルクロン酸である。また、硫酸化グリコサミノグリカンの基本構成単位を構成するアミノ糖は、硫酸化グリコサミノグリカンの種類によって異なるが、D−グルコサミン、D−ガラクトサミン、N−アセチル−D−グルコサミン又はN−アセチル−D−ガラクトサミンである。硫酸化グリコサミノグリカンの基本構成単位を構成するアミノ糖は、硫酸化グリコサミノグリカンの種類によって異なるが、D−グルコサミン、D−ガラクトサミン、N−アセチル−D−ガラクトサミン、又はN−アセチル−D−グルコサミンである。 Specifically, the uronic acid constituting the basic structural unit of sulfated glycosaminoglycan is L-iduronic acid or D-glucuronic acid. The amino sugar constituting the basic constituent unit of sulfated glycosaminoglycan varies depending on the type of sulfated glycosaminoglycan, but is D-glucosamine, D-galactosamine, N-acetyl-D-glucosamine or N-acetyl. -D-galactosamine. The amino sugars that make up the basic building blocks of sulfated glycosaminoglycans vary depending on the type of sulfated glycosaminoglycan, but are D-glucosamine, D-galactosamine, N-acetyl-D-galactosamine, or N-acetyl-. It is D-glucosamine.
硫酸化グリコサミノグリカンの基本構成単位を構成する一方の糖は、ウロン酸又はガラクトースであればよいが、より一層優れたα−SMA産生抑制作用を発揮させるという観点から、好ましくはウロン酸、更に好ましくはD−グルクロン酸が挙げられる。 One sugar constituting the basic structural unit of sulfated glycosaminoglycan may be uronic acid or galactose, but uronic acid is preferable from the viewpoint of exerting an even more excellent α-SMA production inhibitory effect. More preferably, D-glucuronic acid is mentioned.
硫酸化グリコサミノグリカンの基本構成単位を構成する他方のアミノ糖は、前述するものの内、いずれであってもよいが、より一層優れたα−SMA産生抑制作用を発揮させるという観点から、好ましくはN−アセチル−D−ガラクトサミン又はN−アセチル−D−グルコサミン、更に好ましくはN−アセチル−D−ガラクトサミンが挙げられる。 The other amino sugar that constitutes the basic constituent unit of sulfated glycosaminoglycan may be any of the above-mentioned ones, but is preferable from the viewpoint of exerting an even more excellent α-SMA production inhibitory effect. Can be N-acetyl-D-galactosamine or N-acetyl-D-glucosamine, more preferably N-acetyl-D-galactosamine.
硫酸化グリコサミノグリカンにおいて、硫酸化されている部位については、基本構成単位においてグリコシド結合に関与していない水酸基及び/又はアミノ基であればよいが、例えば、基本構成単位を構成するウロン酸又はガラクトースの第2位の水酸基、第3位の水酸基、第4位の水酸基、基本構成単位を構成するアミノ糖の第2位のアミノ基、第3位の水酸基、第4位の水酸基、第6位の水酸基等が挙げられる。 In the sulfated glycosaminoglycan, the site to be sulfated may be a hydroxyl group and / or an amino group not involved in the glycosidic bond in the basic structural unit. For example, uronic acid constituting the basic structural unit. Alternatively, the 2-position hydroxyl group, the 3-position hydroxyl group, the 4-position hydroxyl group of galactose, the 2-position amino group of the amino sugar constituting the basic structural unit, the 3-position hydroxyl group, the 4-position hydroxyl group, and the fourth hydroxyl group. A hydroxyl group at the 6-position can be mentioned.
硫酸化グリコサミノグリカンにおいて硫酸化されている部位の数については、特に制限されないが、例えば、基本構成単位における硫酸化されている部位の数(硫酸基の数)として、1〜6個、好ましくは1〜3個、より好ましくは1又は2個、更に好ましくは2個が挙げられる。 The number of sulfated sites in the sulfated glycosaminoglycan is not particularly limited, but for example, the number of sulfated sites (number of sulfate groups) in the basic structural unit is 1 to 6. The number is preferably 1 to 3, more preferably 1 or 2, and even more preferably 2.
硫酸化グリコサミノグリカンにおいて硫酸化されている部位として、より一層優れたα−SMA産生抑制作用を発揮させるという観点から、好ましくはアミノ糖の第4位及び第6位の水酸基の少なくとも一方、更に好ましくはアミノ糖の第4位及び第6位の水酸基の双方が挙げられる。 From the viewpoint of exerting an even more excellent effect of suppressing α-SMA production as a site that is sulfated in the sulfated glycosaminoglycan, preferably at least one of the hydroxyl groups at the 4- and 6-positions of the amino sugar is used. More preferably, both the 4- and 6-position hydroxyl groups of the amino sugar can be mentioned.
また、硫酸化グリコサミノグリカンの基本構成単位として、より一層優れたα−SMA産生抑制作用を発揮させるという観点から、好ましくは、第4位及び/又は第6位の水酸基が硫酸化されているN−アセチル−D−ガラクトサミンを有するもの、更に好ましくは第4位及び第6位の双方の水酸基が硫酸化されているN−アセチル−D−ガラクトサミンを有するものが挙げられる。 Further, as a basic constituent unit of sulfated glycosaminoglycan, the hydroxyl groups at the 4-position and / or the 6-position are preferably sulfated from the viewpoint of exerting an even more excellent effect of suppressing α-SMA production. Examples thereof include those having N-acetyl-D-galactosamine, and more preferably those having N-acetyl-D-galactosamine in which both the 4- and 6-position hydroxyl groups are sulfated.
本発明で使用される硫酸化グリコサミノグリカンとして、具体的には、以下の酸性多糖が挙げられる:
・コンドロイチン硫酸A(D−グルクロン酸がN−アセチル−D−ガラクトサミンにβ1−3結合によって結合した基本構成単位を有し、N−アセチル−D−ガラクトサミンの第4位の水酸基が硫酸化されている酸性多糖)
・コンドロイチン硫酸B(D−グルクロン酸がN−アセチル−D−ガラクトサミンにβ1−3結合によって結合した基本構成単位とL−イズロン酸がN−アセチル−D−ガラクトサミンにβ1−3結合によって結合した基本構成単位とを有し、N−アセチル−D−ガラクトサミンの第4位の水酸基が硫酸化されている酸性多糖)
・コンドロイチン硫酸C(D−グルクロン酸がN−アセチル−D−ガラクトサミンにβ1−3結合によって結合した基本構成単位を有し、N−アセチル−D−ガラクトサミンの第6位の水酸基が硫酸化されている酸性多糖)
・コンドロイチン硫酸D(D−グルクロン酸がN−アセチル−D−ガラクトサミンにβ1−3結合によって結合した基本構成単位を有し、D−グルクロン酸の第2位の水酸基とN−アセチル−D−ガラクトサミンの第6位の水酸基が硫酸化されている酸性多糖)
・コンドロイチン硫酸E(D−グルクロン酸がN−アセチル−D−ガラクトサミンにβ1−3結合によって結合した基本構成単位を有し、N−アセチル−D−ガラクトサミンの第4位と第6位の水酸基が硫酸化されている酸性多糖)
・ヘパラン硫酸(D−グルクロン酸がN−アセチル−D−ガラクトサミンにβ1−3結合によって結合した基本構成単位とL−イズロン酸がN−アセチル−D−ガラクトサミンにβ1−3結合によって結合した基本構成単位とを有し、D−グルクロン酸及びL−イズロン酸の第2位の水酸基、並びにN−アセチル−D−ガラクトサミンの2位のアミノ酸及び第6位の水酸基が硫酸化されている酸性多糖)
・ケラタン硫酸(D−ガラクトースがN−アセチル−D−ガラクトサミンにβ1−4結合によって結合した基本構成単位を有し、D−ガラクトースの第6位の水酸基、並びにN−アセチル−D−ガラクトサミンの2位のアミノ基及び第6位の水酸基が硫酸化されている酸性多糖)
Specific examples of the sulfated glycosaminoglycan used in the present invention include the following acidic polysaccharides:
-Chondroitin sulfate A (D-glucuronic acid has a basic structural unit bonded to N-acetyl-D-galactosamine by β1-3 bond, and the hydroxyl group at the 4-position of N-acetyl-D-galactosamine is sulfated. Acidic polysaccharides)
-Basic building block of chondroitin sulfate B (D-glucuronic acid bound to N-acetyl-D-galactosamine by β1-3 bond) and L-iduronic acid bound to N-acetyl-D-galactosamine by β1-3 bond An acidic polysaccharide that has a constituent unit and the hydroxyl group at the 4-position of N-acetyl-D-galactosamine is sulfated)
-Chondroitin sulfate C (D-glucuronic acid has a basic structural unit bonded to N-acetyl-D-galactosamine by β1-3 bond, and the hydroxyl group at the 6-position of N-acetyl-D-galactosamine is sulfated. Acidic polysaccharides)
-Chondroitin sulfate D (D-glucuronic acid has a basic structural unit bonded to N-acetyl-D-galactosamine by β1-3 bond, and has a hydroxyl group at the 2-position of D-glucuronic acid and N-acetyl-D-galactosamine. Acidic polysaccharide in which the hydroxyl group at the 6th position is sulfated)
-Chondroitin sulfate E (D-glucuronic acid has a basic structural unit bonded to N-acetyl-D-galactosamine by β1-3 bond, and the hydroxyl groups at the 4- and 6-positions of N-acetyl-D-galactosamine are Acidic polysaccharides that are sulfated)
-Heparan sulfate (basic constituent unit in which D-glucuronic acid is bound to N-acetyl-D-galactosamine by β1-3 bond and L-iduronic acid is bound to N-acetyl-D-galactosamine by β1-3 bond) An acidic polysaccharide having a unit and in which the 2-position hydroxyl group of D-glucuronic acid and L-iduronic acid, and the 2-position amino acid and 6-position hydroxyl group of N-acetyl-D-galactosamine are sulfated).
-Keratan sulfate (D-galactose has a basic structural unit bonded to N-acetyl-D-galactosamine by β1-4 bond, the hydroxyl group at the 6-position of D-galactose, and 2 of N-acetyl-D-galactosamine. Acidic polysaccharide in which the amino group at the position and the hydroxyl group at the 6th position are sulfated)
これらの硫酸化グリコサミノグリカンは、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。 These sulfated glycosaminoglycans may be used alone or in combination of two or more.
本発明で使用される硫酸化グリコサミノグリカンの重合度については、特に制限されないが、例えば、基本構成単位(2つの糖残基からなる構成単位)が2〜300程度、好ましくは5〜200程度、更に好ましくは10〜150程度重合しているものが挙げられる。 The degree of polymerization of the sulfated glycosaminoglycan used in the present invention is not particularly limited, but for example, the basic structural unit (constituent unit consisting of two sugar residues) is about 2 to 300, preferably 5 to 200. The degree of polymerization, more preferably about 10 to 150, may be mentioned.
また、硫酸化グリコサミノグリカンの塩については、薬学的に許容されることを限度として特に制限されないが、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩;カルシウム塩、マグネシウム塩、鉄塩、マンガン塩等の金属塩;アンモニウム塩等の塩が挙げられる。これらの硫酸化グリコサミノグリカンの塩は、1種単独で使用してもよく、また2種以上を組み合わせて使用してもよい。 The salt of sulfated glycosaminoglycan is not particularly limited as long as it is pharmaceutically acceptable, but for example, alkali metal salts such as sodium salt and potassium salt; calcium salt, magnesium salt, iron salt, etc. Metal salts such as manganese salts; salts such as ammonium salts can be mentioned. These sulfated glycosaminoglycan salts may be used alone or in combination of two or more.
本発明のα−SMA産生抑制剤では、硫酸化グリコサミノグリカン及びその塩の中から、1種を選択して単独で使用してもよく、2種以上を組み合わせて使用してもよい。 In the α-SMA production inhibitor of the present invention, one of sulfated glycosaminoglycans and salts thereof may be selected and used alone, or two or more thereof may be used in combination.
本発明で使用される硫酸化グリコサミノグリカン及び/又はその塩は、動物から抽出し、必要に応じて精製して得られたものであってもよく、また化学合成したものや遺伝子工学的手法を用いて製造したものであってもよい。 The sulfated glycosaminoglycan and / or a salt thereof used in the present invention may be obtained by extracting from an animal and purifying as necessary, chemically synthesized or genetically engineered. It may be manufactured by a method.
本発明で使用される硫酸化グリコサミノグリカン及びその塩の中でも、より一層優れたα−SMA産生抑制作用を発揮させるという観点から、好ましくは、コンドロイチン硫酸A、コンドロイチン硫酸C、コンドロイチン硫酸E、ヘパラン硫酸、及びそれらの塩;更に好ましくはコンドロイチン硫酸E及びその塩が挙げられる。 Among the sulfated glycosaminoglycans and salts thereof used in the present invention, chondroitin sulfate A, chondroitin sulfate C, chondroitin sulfate E, are preferable from the viewpoint of exerting an even more excellent effect of suppressing α-SMA production. Heparan sulfate and salts thereof; more preferably chondroitin sulfate E and salts thereof.
本発明のα−SMA産生抑制剤において、硫酸化グリコサミノグリカン及び/又はその塩の含有量については、特に制限されず、該剤の製剤形態や投与形態等に応じて適宜設定すればよいが、例えば、0.01〜5重量%が挙げられる。より具体的には、本発明のα−SMA産生抑制剤が皮膚外用剤の場合であれば、硫酸化グリコサミノグリカン及び/又はその塩の含有量として、通常0.05〜3重量%、好ましくは0.1〜3重量%、更に好ましくは0.1〜1重量%が挙げられる。 In the α-SMA production inhibitor of the present invention, the content of sulfated glycosaminoglycan and / or a salt thereof is not particularly limited and may be appropriately set according to the formulation form, administration form and the like of the agent. However, for example, 0.01 to 5% by weight can be mentioned. More specifically, when the α-SMA production inhibitor of the present invention is an external preparation for skin, the content of sulfated glycosaminoglycan and / or a salt thereof is usually 0.05 to 3% by weight. It is preferably 0.1 to 3% by weight, more preferably 0.1 to 1% by weight.
[その他の成分]
本発明のα−SMA産生抑制剤は、前記硫酸化グルコサミノグリカンの他に、必要に応じて、他の薬理成分を含有していてもよい。このような薬理成分としては、例えば、抗ヒスタミン剤(グリチルリチン酸二カリウム、グリチルリチン酸、ジフェンヒドラミン、塩酸ジフェンヒドラミン等)、局所麻酔剤(プロカイン、テトラカイン、ブピパカイン、メピパカイン、クロロプロカイン、プロパラカイン、メプリルカイン又はこれらの塩、オルソカイン、オキセサゼイン、オキシポリエントキシデカン、ロートエキス、ペルカミンパーゼ、テシットデシチン等)、抗炎症剤(アラントイン、インドメタシン、フェルビナク、ジクロフェナクナトリウム、ロキソプロフェンナトリウム等)、皮膚保護剤(コロジオン、ヒマシ油等)、血行促進成分(ノニル酸ワニリルアミド、ニコチン酸ベンジルエステル、カプサイシン、トウガラシエキス等)、清涼化剤(メントール、カンフル等)、ビタミン類(ビタミンA等)、ムコ多糖類(コンドロイチン硫酸ナトリウム、グルコサミン等)等が挙げられる。
[Other ingredients]
The α-SMA production inhibitor of the present invention may contain other pharmacological components in addition to the sulfated glycosaminoglycan, if necessary. Examples of such pharmacological components include anti-histamines (dipotassium glycyrrhizinate, glycyrrhizic acid, difenhydramine, diphenhydramine hydrochloride, etc.), local anesthetics (procaine, tetracaine, bupipacaine, mepipacine, chloroprocaine, proparacaine, meprilcaine, or salts thereof. , Orthokine, oxesazein, oxypolyentoxydecane, funnel extract, percaminpase, tesitdecitin, etc.), anti-inflammatory agents (alantin, indomethacin, fervinac, diclofenac sodium, loxoprofen sodium, etc.), skin protectants (corodion, castor oil, etc.), blood circulation promotion Ingredients (nonyl acid vanillylamide, nicotinic acid benzyl ester, capsaicin, capsicum extract, etc.), refreshing agents (menthol, camphor, etc.), vitamins (vitamin A, etc.), mucopolysaccharides (chondroitin sodium sulfate, glucosamine, etc.), etc. Be done.
また、本発明のα−SMA産生抑制剤は、所望の製剤形態にするために、必要に応じて、基剤や添加剤が含まれていてもよい。このような基剤や添加剤については、薬学的に許容されることを限度として特に制限されないが、例えば、水、低級アルコール(エタノール、イソプロパノール等)、多価アルコール(グリセリン、プロピレングリコール、ジプロピレングリコール、1,3−ブチレングリコール等)等の水性基剤;油類(オリーブ油、サフラワー油、大豆油、つばき油、とうもろこし油、なたね油、ひまわり油、綿実油、落花生油、ラード、スクワラン、魚油等)、鉱物油(流動パラフィン、パラフィン、ゲル化炭化水素、ワセリン等)、ワックス類・ロウ類(ミツロウ、カルナウバロウ、キャンデリラロウ、セレシン、ライスワックス、マイクロクリスタリンワックス等)、エステル油(ミリスチン酸イソプロピル、アジピン酸イソプロピル、セバシン酸ジエチル、セバシン酸イソプロピル、パルミチン酸イソプロピル、パルミチン酸セチル、オレイン酸エチル等)、脂肪酸アルキルエステル、脂肪酸(ステアリン酸、オレイン酸、パルミチン酸、ベヘン酸、リノール酸、ラノリン等)、脂肪酸エステル(パルミチン酸セチル、パルミチン酸イソプロピル、リノール酸エチル等)、高級アルコール(ステアリルアルコール、セタノール、ベヘニルアルコール、ミリスチルアルコール、オレイルアルコール、ヘキサデシルアルコール、ラノリンアルコール等)、コレステロール、トリ2−エチルヘキサン酸グリセリル、2−エチルヘキサン酸セチル、シリコーンオイル(ジメチルポリシロキサン、環状シリコーン等)等の油性基剤;POE(10〜50モル)フィトステロールエーテル、POE(10〜50モル)ジヒドロコレステロールエーテル、POE(10〜50モル)2−オクチルドデシルエーテル、POE(10〜50モル)デシルテトラデシルエーテル、POE(10〜50モル)オレイルエーテル、POE(2〜50モル)セチルエーテル、POE(5〜50モル)ベヘニルエーテル、POE(5〜30モル)ポリオキシプロピレン(5〜30モル)2−デシルテトラデシルエーテル、POE(10〜50モル)ポリオキシプロピレン(2〜30モル)セチルエーテルなどのポリオキシエチレンアルキルエーテル、これらのリン酸・リン酸塩(POEセチルエーテルリン酸ナトリウムなど)、POE(20〜60モル)ソルビタンモノオレート、POE(10〜60モル)ソルビタンモノイソステアレート、POE(10〜80モル)グリセリルモノイソステアレート、POE(10〜30モル)グリセリルモノステアレート、POE(20〜100モル)・ポリオキシプロピレン変性シリコーン、POE・アルキル変性シリコーン、モノラウリン酸ポリエチレングリコール、モノパルミチン酸ポリエチレングリコール、モノステアリン酸ポリエチレングリコール、ジラウリン酸ポリエチレングリコール、ジパルミチン酸ポリエチレングリコール、ジステアリン酸ポリエチレングリコール、ジオレイン酸ポリエチレングリコール、ジリシノレイン酸ポリエチレングリコール、ポリオキシエチレン硬化ヒマシ油(5〜100)、ポリソルベート(20〜85)、グリセリン脂肪酸エステル(モノステアリン酸グリセリン等)、水素添加大豆リン脂質、水素添加ラノリンアルコール等の界面活性剤;清涼化剤(メントール、カンフル、ボルネオール、ハッカ水、ハッカ油等)、防腐剤(メチルパラベン、プロピルパラベン、安息香酸、安息香酸ナトリウム、ソルビン酸等)、着香剤(シトラール、1,8−シオネール、シトロネラール、ファルネソール等)、着色剤(タール色素(褐色201号、青色201号、黄色4号、黄色403号等)、カカオ色素、クロロフィル、酸化アルミニウム等)、粘稠剤(カルボキシビニルポリマー、ヒプロメロース、ポリビニルピロリドン、アルギン酸ナトリウム、エチルセルロース、カルボキシメチルセルロースナトリウム、キサンタンガム、カラギーナン等)、pH調整剤(リン酸、塩酸、クエン酸、クエン酸ナトリウム、コハク酸、酒石酸、水酸化ナトリウム、水酸化カリウム、トリエタノールアミン、トリイソプロパノールアミン等)、湿潤剤(dl−ピロリドンカルボン酸ナトリウム液、D−ソルビトール液、マクロゴール等)、安定化剤(ジブチルヒドロキシトルエン、ブチルヒドロキシアニソール、エデト酸ナトリウム、メタリン酸ナトリウム、L−アルギニン、L−アスパラギン酸、DL−アラニン、グリシン、エリソルビン酸ナトリウム、没食子酸プロピル、亜硫酸ナトリウム、二酸化硫黄、クロロゲン酸、カテキン、ローズマリー抽出物等)、酸化防止剤、紫外線吸収剤、キレート剤、粘着剤、緩衝剤、溶解補助剤、可溶化剤、保存剤等の添加剤が挙げられる。 In addition, the α-SMA production inhibitor of the present invention may contain a base or an additive, if necessary, in order to obtain a desired formulation form. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable, but for example, water, lower alcohols (ethanol, isopropanol, etc.), polyhydric alcohols (glycerin, propylene glycol, dipropylene, etc.) Aqueous bases such as glycol, 1,3-butylene glycol, etc.; oils (olive oil, paraffin oil, soybean oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil, lard, squalane, fish oil, etc. ), Mineral oil (liquid paraffin, paraffin, gelled hydrocarbon, vaseline, etc.), waxes / waxes (mitsurou, carnauba wax, candelilla wax, selecin, rice wax, microcrystallin wax, etc.), ester oil (isopropyl myristate, etc.) , Isopropyl adipate, diethyl sebacate, isopropyl sebacate, isopropyl palmitate, cetyl palmitate, ethyl oleate, etc.), fatty acid alkyl esters, fatty acids (stearic acid, oleic acid, palmitic acid, bechenic acid, linoleic acid, lanolin, etc.) ), Fatty acid esters (cetyl palmitate, isopropyl palmitate, ethyl linoleate, etc.), higher alcohols (stearyl alcohol, cetanol, behenyl alcohol, myristyl alcohol, oleyl alcohol, hexadecyl alcohol, lanolin alcohol, etc.), cholesterol, tri2-ethyl Oily bases such as glyceryl hexanoate, cetyl 2-ethylhexanoate, silicone oil (dimethylpolysiloxane, cyclic silicone, etc.); POE (10-50 mol) phytosterol ether, POE (10-50 mol) dihydrocholesterol ether, POE (10-50 mol) 2-octyldodecyl ether, POE (10-50 mol) decyltetradecyl ether, POE (10-50 mol) oleyl ether, POE (2-50 mol) cetyl ether, POE (5-50 mol) ) Polyoxyethylene such as behenyl ether, POE (5-30 mol) polyoxypropylene (5-30 mol) 2-decyltetradecyl ether, POE (10-50 mol) polyoxypropylene (2-30 mol) cetyl ether Alcohol ethers, these phosphates and phosphates (POE cetyl ether sodium phosphate, etc.), POE (20-60 mol) sorbitan monooleate, POE (10-60 mol) sorbitan monoisostearate, POE (10-60 mol) 80 mol) glyceryl monoisostearate, POE (10-30 mol) glyceryl monostearate, POE (20-100 mol) polyoxypropylene-modified silicone, POE-alkyl-modified silicone, polyethylene glycol monolaurate, polyethylene monopalmitate Glycol, polyethylene glycol monostearate, polyethylene glycol dilaurate, polyethylene glycol dipalmitate, polyethylene glycol distearate, polyethylene glycol dioleate, polyethylene glycol diricinoleate, polyoxyethylene hydrogenated castor oil (5-100), polysorbate (20) ~ 85), Surfactants such as glycerin fatty acid esters (glycerin monostearate, etc.), hydrogenated soybean phospholipids, hydrogenated lanolin alcohol; refreshing agents (menthol, camphor, borneol, peppermint water, peppermint oil, etc.), antiseptic Agents (methylparaben, propylparaben, benzoic acid, sodium benzoate, sorbic acid, etc.), flavoring agents (citral, 1,8-cyonel, citronellal, farnesol, etc.), colorants (tar pigments (brown 201, blue 201, etc.) , Yellow No. 4, Yellow No. 403, etc.), cocoa pigment, chlorophyll, aluminum oxide, etc.), viscous agent (carboxyvinyl polymer, hypromerose, polyvinylpyrrolidone, sodium alginate, ethyl cellulose, sodium carboxymethyl cellulose, xanthan gum, carrageenan, etc.) Conditioning agent (phosphate, hydrochloric acid, citrate, sodium citrate, succinic acid, tartrate acid, sodium hydroxide, potassium hydroxide, triethanolamine, triisopropanolamine, etc.), wetting agent (dol-pyrrolidone sodium carboxylate solution, D) -Solvitol solution, macrogol, etc.), stabilizers (dibutylhydroxytoluene, butylhydroxyanisole, sodium edetate, sodium metaphosphate, L-arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbinate, gallic acid Addition of propyl, sodium sulfite, sulfur dioxide, chlorogenic acid, catechin, rosemary extract, etc.), antioxidants, UV absorbers, chelating agents, pressure-sensitive agents, buffers, solubilizers, solubilizers, preservatives, etc. Agents can be mentioned.
[製剤形態]
本発明のα−SMA産生抑制剤の剤型は、皮膚外用剤、内服剤、注射剤、点滴剤等のいずれであってもよく、該剤の具体的用途に応じて適宜設定すればよいが、より一層優れたα−SMA産生抑制作用を発揮させるという観点から、好ましくは皮膚外用剤が挙げられる。
[Formulation form]
The dosage form of the α-SMA production inhibitor of the present invention may be any of an external preparation for skin, an internal preparation, an injection, a drip infusion, etc., and may be appropriately set according to the specific use of the preparation. From the viewpoint of exerting an even more excellent effect of suppressing α-SMA production, an external preparation for skin is preferable.
本発明のα−SMA産生抑制剤を皮膚外用剤として使用する場合、その形状については、経皮適用できることを限度として特に制限されないが、例えば、液状、固形状、半固形状(ゲル状、軟膏状、ペースト状)等が挙げられる。 When the α-SMA production inhibitor of the present invention is used as an external preparation for skin, its shape is not particularly limited as long as it can be applied transdermally, but for example, it is liquid, solid, semi-solid (gel, ointment). Shape, paste shape) and the like.
また、本発明のα−SMA産生抑制剤を皮膚外用剤として使用する場合、その製剤形態については、経皮適用できることを限度として特に制限されないが、例えば、皮膚外用医薬品、皮膚外用医薬部外品、化粧料、皮膚洗浄料等が挙げられる。本発明のα−SMA産生抑制剤を皮膚外用剤にする場合の製剤形態として、具体的には、クリーム剤、ローション剤、ジェル剤、乳液剤、液剤、貼付剤、エアゾール剤、軟膏剤、パック剤等の皮膚外用医薬品;クリーム剤、ローション剤、ジェル剤、乳液剤、液剤、貼付剤、エアゾール剤、軟膏剤、パック剤等の皮膚外用医薬部外品;クリーム剤、ローション剤、ジェル剤、乳液剤、液剤、軟膏剤、パック剤等の化粧料;ボディーシャンプー、ヘアシャンプー、リンス等の皮膚洗浄料等が挙げられる。これらの製剤形態の中でも、好ましくは皮膚外用医薬品、更に好ましくはクリーム剤、ローション剤、ジェル剤、乳液剤、パック剤が挙げられる。 Further, when the α-SMA production inhibitor of the present invention is used as an external preparation for skin, the formulation form thereof is not particularly limited as long as it can be applied transdermally, but for example, an external preparation for skin and a quasi-drug for external use on skin. , Cosmetics, skin cleaning agents, etc. Specific examples of the formulation form when the α-SMA production inhibitor of the present invention is used as an external preparation for skin are creams, lotions, gels, emulsions, liquids, patches, aerosols, ointments, and packs. Topical skin preparations such as preparations; creams, lotions, gels, emulsions, liquids, patches, aerosols, ointments, packs and other external medicines for skin; creams, lotions, gels, Cosmetics such as emulsions, liquids, ointments, and packs; skin lotions such as body shampoos, hair shampoos, and rinses can be mentioned. Among these preparation forms, a skin external medicine is preferable, and a cream, lotion, gel, emulsion, and pack are more preferable.
[用途・用量]
本発明のα−SMA産生抑制剤は、α−SMAの発現を抑制できるので、α−SMAの過剰な発現が一因となっている疾患や症状、α−SMAが関与している疾患や症状の予防又は治療に有効である。具体的には、肥厚性瘢痕やケロイド等の皮膚創傷治癒異常では、α−SMAの過剰な発現が一因となっていることが知られているので、本発明のα−SMA産生抑制剤は、これらの皮膚創傷治癒異常の予防又は治療に使用できる。更に、α−SMAは、腫瘍細胞の転移や骨粗鬆症にも関与していることが知られているので、本発明のα−SMA産生抑制剤は、腫瘍の転移や骨粗鬆症の予防又は治療にも使用することができる。
[Use / Dosage]
Since the α-SMA production inhibitor of the present invention can suppress the expression of α-SMA, diseases and symptoms caused by excessive expression of α-SMA, and diseases and symptoms associated with α-SMA. It is effective in the prevention or treatment of. Specifically, it is known that excessive expression of α-SMA is one of the causes of abnormal skin wound healing such as hypertrophic scars and keloids. Therefore, the α-SMA production inhibitor of the present invention is used. , Can be used for the prevention or treatment of these skin wound healing abnormalities. Furthermore, since α-SMA is known to be involved in tumor cell metastasis and osteoporosis, the α-SMA production inhibitor of the present invention is also used for prevention or treatment of tumor metastasis and osteoporosis. can do.
とりわけ、本発明のα−SMA産生抑制剤は、傷痕部の真皮由来の繊維芽細胞におけるα−SMAの発現を効果的に抑制できるので、当該細胞のα−SMAの過剰な発現が一因となっている皮膚創傷治癒異常(肥厚性瘢痕やケロイド等)の予防又は治療用途に特に好適に使用できる。 In particular, the α-SMA production inhibitor of the present invention can effectively suppress the expression of α-SMA in dermis-derived fibroblasts at the scar site, and thus the excessive expression of α-SMA in the cells is one of the causes. It can be particularly suitably used for the prevention or treatment of abnormal skin wound healing (hypertrophic scars, keloids, etc.).
また、本発明のα−SMA産生抑制剤の用量については、投与方法、製剤形態、適用する症状の程度等に応じて適宜設定すればよい。例えば、本発明のα−SMA産生抑制剤を皮膚外用剤として使用する場合であれば、その用量の一例として、1回当たり、皮膚1cm2当たり、硫酸化グルコサミノグリカン及び/又はその塩が0.1〜3mg程度となる量で、1日1〜数回程度の頻度が挙げられる。 The dose of the α-SMA production inhibitor of the present invention may be appropriately set according to the administration method, formulation form, degree of symptom to be applied, and the like. For example, when the α-SMA production inhibitor of the present invention is used as an external preparation for skin, as an example of the dose, sulfated glucosaminoglycan and / or a salt thereof may be used per 1 cm 2 of the skin. The amount is about 0.1 to 3 mg, and the frequency is about 1 to several times a day.
以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。 The present invention will be described in more detail with reference to Examples below, but the present invention is not limited thereto.
試験例1
硫酸化グルコサミノグリカンが傷痕部の真皮由来の繊維芽細胞のα−SMA発現に与える影響を評価するために以下の実験を行った。
Test Example 1
The following experiments were conducted to evaluate the effect of sulfated glycosaminoglycan on α-SMA expression of dermis-derived fibroblasts in the scar area.
1.実験材料
(細胞)
本試験では、ヒト傷痕部の真皮由来の繊維芽細胞(HSF)(コスモバイオ株式会社、HYPERTROPHIC SCAR FIBROBLAST; ADULT LEFT、CRC−HSF105−1)を使用した。
1. 1. Experimental material (cells)
In this study, dermis-derived fibroblasts (HSF) from human scars (Cosmo Bio Co., Ltd., HYPERTROPHIC SCAR FIBROBLAST; ADULT LEFT, CRC-HSF105-1) were used.
(培地)
ウシ胎児血清を10容量%となるように添加したD-MEM/Ham's F-12(和光純薬工業株式会社、042−30555)を使用した。
(Culture medium)
D-MEM / Ham's F-12 (Wako Pure Chemical Industries, Ltd., 042-30555) to which fetal bovine serum was added so as to be 10% by volume was used.
(試薬)
ヒトTGF−β(Human Transforming Growth Factor−β1):ヒトTGF−β(PERPROTECH、PTI−100−21C−10)を脱イオン蒸留水で希釈して使用した。なお、ヒトTGF−βは、HSFにおけるα−SMAの発現を誘導することが知られている成分である。
ヘパラン硫酸:ヘパラン硫酸(フナコシ株式会社、GAG−HS01)を脱イオン蒸留水で希釈して使用した。
コンドロイチン硫酸Aナトリウム:コンドロイチン硫酸Aナトリウム(和光純薬工業株式会社、ニワトリ軟骨由来(037−24391))を脱イオン蒸留水で希釈して使用した。
コンドロイチン硫酸Cナトリウム:コンドロイチン硫酸Cナトリウム(和光純薬工業株式会社、(032−14613))を脱イオン蒸留水で希釈して使用した。
コンドロイチン硫酸Eナトリウム:コンドロイチン硫酸Eナトリウム(和光純薬工業株式会社、イカ軟骨由来(034−23061))を脱イオン蒸留水で希釈して使用した。
(reagent)
Human TGF-β (Human Transforming Growth Factor-β1) : Human TGF-β (PERPROTECH, PTI-100-21C-10) was diluted with deionized distilled water and used. Human TGF-β is a component known to induce the expression of α-SMA in HSF.
Heparan sulfate : Heparan sulfate (Funakoshi Co., Ltd., GAG-HS01) was diluted with deionized distilled water before use.
Sodium chondroitin sulfate: Sodium chondroitin sulfate (Wako Pure Chemical Industries, Ltd., derived from chicken cartilage (037-24391)) was diluted with deionized distilled water and used.
C sodium chondroitin sulfate: C sodium chondroitin sulfate (Wako Pure Chemical Industries, Ltd., (032-14613)) was diluted with deionized distilled water and used.
E-sodium chondroitin sulfate: E-sodium chondroitin sulfate (Wako Pure Chemical Industries, Ltd., derived from squid cartilage (034-23061)) was diluted with deionized distilled water and used.
2.実験方法
HSFを1.0×105cells/mlとなるように培地に添加した細胞懸濁液0.5mlを24穴プレ−トの各穴に撒き、更にTGF−βを最終濃度が2 ng/mLになるように加え、37℃、5%CO2条件下で48時間インキュベ−タ−にて培養した。48時間の培養後、最終濃度が1 mg/mL又は0.2 mg/mLとなるように硫酸化グルコサミノグリカンを添加した。硫酸化グルコサミノグリカンの添加後に、37℃、5%CO2条件下で9日間インキュベ−タ−にて培養した後に、各穴に、1×Sample buffer(ドデシル硫酸ナトリウム6重量%、Tris-HCl 0.25M、グリセロール50重量%、ブロモフェノールブルー0.1重量%を含有する3×Sample bufferをイオン交換水で3倍に希釈したもの)200μL及び2−メルカプトエタノール2μLを加え、細胞を回収した。得られた細胞回収液に対して、ボルテックスを行い、更にソニケ−ションを行った後に、煮沸することにより、細胞溶解液を得た。得られた細胞溶解液についてウエスタンブロッティングを行い、α−SMAの発現量を求めた。α−SMA発現量は、内部標準であるβ−actinの発現量と比較して補正することにより求めた。また、コントロールとして、硫酸化グルコサミノグリカンを添加しなかったこと以外は、前記と同条件で試験を行い、α−SMAの発現量を求めた。なお、本試験では、同一条件での試験を5つの穴で行い、得られたα−SMAの発現量の平均値を算出することによって評価した。
2. 2. experimental method
Sprinkle 0.5 ml of cell suspension added to the medium to 1.0 × 10 5 cells / ml of HSF into each hole of the 24-well plate, and further add TGF-β to a final concentration of 2 ng / mL. In addition, the cells were cultured in an incubator for 48 hours under the conditions of 37 ° C. and 5% CO 2 . After culturing for 48 hours, sulfated glycosaminoglycans were added to a final concentration of 1 mg / mL or 0.2 mg / mL. After addition of sulfated glucosaminoglycan, after culturing in an incubator for 9 days under 37 ° C. and 5% CO 2 conditions, 1 × Sample buffer (6 wt% sodium dodecyl sulfate, Tris-) was added to each hole. 200 μL of 3 × Sample buffer containing 0.25 M HCl, 50% by weight of glycerol and 0.1% by weight of bromophenol blue diluted 3-fold with ion-exchanged water) and 2 μL of 2-mercaptoethanol were added, and cells were collected. The obtained cell recovery solution was vortexed, further sonicated, and then boiled to obtain a cell lysate. Western blotting was performed on the obtained cell lysate to determine the expression level of α-SMA. The expression level of α-SMA was determined by adjusting the expression level by comparing with the expression level of β-actin, which is an internal standard. In addition, as a control, the test was carried out under the same conditions as above except that sulfated glucosaminoglycan was not added, and the expression level of α-SMA was determined. In this test, the test was conducted under the same conditions in five holes, and the average value of the obtained α-SMA expression levels was calculated for evaluation.
3.実験結果
得られた結果を表1に示す。この結果、TGF−βによってα−SMAの発現が誘導されたHDFに硫酸化グルコサミノグリカンを共存させることにより、α−SMAの発現量を低減できることが確認された。特に、基本構成単位中のN−アセチルガラクトサミンの4位と6位に硫酸基を持つコンドロイチン硫酸Eは、α−SMAの発現を顕著に抑制できることが明らかとなった。
3. 3. Experimental Results Table 1 shows the obtained results. As a result, it was confirmed that the expression level of α-SMA can be reduced by coexisting sulfated glycosaminoglycan with HDF in which the expression of α-SMA was induced by TGF-β. In particular, it was revealed that chondroitin sulfate E having a sulfate group at the 4- and 6-positions of N-acetylgalactosamine in the basic structural unit can remarkably suppress the expression of α-SMA.
処方例
α−SMA産生抑制剤として、表2〜3に示す組成のクリーム剤(処方例1〜8)、表4に示すローション剤(処方例9〜14)、表5に示すジェル剤(処方例15〜19)、及び表6〜7に示す乳液剤(処方例20〜29)を調製した。これらの製剤は、いずれも、前記試験例1の場合と同様に、α−SMAの発現量を抑制させる効果が期待され、α−SMAの産生抑制に有効である。
Formulation Examples As α-SMA production inhibitors, creams having the compositions shown in Tables 2 to 3 (Prescription Examples 1 to 8), lotions shown in Table 4 (Prescription Examples 9 to 14), and gel agents shown in Table 5 (formulations). Examples 15-19) and the emulsions shown in Tables 6-7 (Prescription Examples 20-29) were prepared. All of these preparations are expected to have an effect of suppressing the expression level of α-SMA as in the case of Test Example 1, and are effective in suppressing the production of α-SMA.
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016149624A JP6815782B2 (en) | 2016-07-29 | 2016-07-29 | α-SMA production inhibitor |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016149624A JP6815782B2 (en) | 2016-07-29 | 2016-07-29 | α-SMA production inhibitor |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018016596A JP2018016596A (en) | 2018-02-01 |
JP6815782B2 true JP6815782B2 (en) | 2021-01-20 |
Family
ID=61081410
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016149624A Active JP6815782B2 (en) | 2016-07-29 | 2016-07-29 | α-SMA production inhibitor |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6815782B2 (en) |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002205937A (en) * | 2000-11-13 | 2002-07-23 | Lion Corp | Emulsified composition |
JP2005082491A (en) * | 2003-09-04 | 2005-03-31 | Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho | Immunosuppresant |
WO2010086754A2 (en) * | 2009-01-30 | 2010-08-05 | Beiersdorf Ag | Cosmetic or dermatological preparation comprising collagen, chitosan, glycosylaminoglycan and cell growth promoting peptide and/or cellular complex |
AU2011248566B2 (en) * | 2010-04-28 | 2015-11-26 | Sandeep Kathju | Compositions and methods for reduced scarring and for treatment of fibrosis |
WO2012008457A1 (en) * | 2010-07-12 | 2012-01-19 | ロート製薬株式会社 | Composition for external application |
US20140072613A1 (en) * | 2012-09-10 | 2014-03-13 | Cynthia Lander | Compositions and Methods for Treating Cutaneous Scarring |
WO2014098249A1 (en) * | 2012-12-21 | 2014-06-26 | 国立大学法人名古屋大学 | Composition having tissue repairing activity and utilization thereof |
US20150024014A1 (en) * | 2013-03-14 | 2015-01-22 | Marine Polymer Technologies, Inc. | Treatment of disease with poly-n-acetylglucosamine nanofibers |
JP5897164B2 (en) * | 2014-07-22 | 2016-03-30 | 小林製薬株式会社 | Composition for external use |
SG11201704085QA (en) * | 2014-11-19 | 2017-06-29 | Agency Science Tech & Res | Heparan sulphates for use in repair and/or regeneration of skin |
-
2016
- 2016-07-29 JP JP2016149624A patent/JP6815782B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
JP2018016596A (en) | 2018-02-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4542300B2 (en) | Hyaluronic acid accumulation promoter | |
KR20190037229A (en) | A synergistic antifungal composition and method thereof | |
EP3120831A1 (en) | Topical delivery of skin compositions having low ph | |
JP6666068B2 (en) | External composition | |
JP2013521300A (en) | Compositions and methods for the treatment of skin diseases and disorders using antimicrobial peptide sequestering compounds | |
JPH0967266A (en) | Inhibitor of hyaluronidase | |
JP5891651B2 (en) | Skin preparation for normalization of stratum corneum cell differentiation | |
CN115487112A (en) | Anti-inflammatory soothing composition for skin | |
JP2007262012A (en) | Hyaluronic acid production promoter, skin external preparation containing the hyaluronic acid production promoter, cosmetic, quasi drug, chapped skin ameliorating agent, and wrinkle ameliorating agent | |
JP6725207B2 (en) | Skin pigmentation inhibitor | |
WO2006090940A1 (en) | Composγπon for prevention and treatment of stretch mark comprising citric acid, zinc and arginine | |
DK2306999T3 (en) | Compositions for the treatment of rosacea comprising chitosan and a dicarboxylsyreamid | |
JP6815782B2 (en) | α-SMA production inhibitor | |
JP7361448B2 (en) | Transglutaminase expression promoter | |
JP2018203674A (en) | Sebum secretion promoter and external composition | |
JP6656890B2 (en) | Filaggrin production promoter | |
JP6698318B2 (en) | Ceramide synthesis accelerator | |
ES2884787T3 (en) | Use of rhamnose derivatives as antifungal agents | |
JP6851139B2 (en) | Topical composition | |
JP2019006697A (en) | Active oxygen scavenger | |
JP7153429B2 (en) | Active oxygen scavenging agent | |
KR101567735B1 (en) | Composition for preventing or improving or treating psoriasis comprising immunomodulating agent and glucosamine | |
JP6735587B2 (en) | External composition | |
JP2017088541A (en) | Abnormal scar formation inhibitor | |
KR102204367B1 (en) | Cosmetic compositions for improving skin wrinkle |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20170208 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190604 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20200626 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200714 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200911 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201111 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20201124 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20201223 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6815782 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |