CN1210460A - 促进指甲生长的配剂 - Google Patents
促进指甲生长的配剂 Download PDFInfo
- Publication number
- CN1210460A CN1210460A CN97192082A CN97192082A CN1210460A CN 1210460 A CN1210460 A CN 1210460A CN 97192082 A CN97192082 A CN 97192082A CN 97192082 A CN97192082 A CN 97192082A CN 1210460 A CN1210460 A CN 1210460A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- horizon
- fingernail
- azoles
- nial polish
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000036562 nail growth Effects 0.000 title abstract description 14
- 238000002360 preparation method Methods 0.000 title description 4
- 230000004936 stimulating effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 210000004905 finger nail Anatomy 0.000 claims description 59
- 238000011282 treatment Methods 0.000 claims description 33
- 230000009471 action Effects 0.000 claims description 18
- 230000000843 anti-fungal effect Effects 0.000 claims description 18
- 229940121375 antifungal agent Drugs 0.000 claims description 18
- 150000003851 azoles Chemical class 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 14
- -1 pyridone ketone Chemical class 0.000 claims description 12
- 229920001577 copolymer Polymers 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 230000001196 vasorelaxation Effects 0.000 claims description 7
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 6
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 5
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 5
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- LEZWWPYKPKIXLL-UHFFFAOYSA-N 1-{2-(4-chlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound C1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 LEZWWPYKPKIXLL-UHFFFAOYSA-N 0.000 claims description 4
- 229920002160 Celluloid Polymers 0.000 claims description 4
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 4
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 claims description 4
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- SCKYRAXSEDYPSA-UHFFFAOYSA-N ciclopirox Chemical compound ON1C(=O)C=C(C)C=C1C1CCCCC1 SCKYRAXSEDYPSA-UHFFFAOYSA-N 0.000 claims description 4
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 229960003913 econazole Drugs 0.000 claims description 4
- 229960001783 nicardipine Drugs 0.000 claims description 4
- 229960001597 nifedipine Drugs 0.000 claims description 4
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 229960001476 pentoxifylline Drugs 0.000 claims description 4
- OIQJEQLSYJSNDS-UHFFFAOYSA-N piroctone Chemical compound CC(C)(C)CC(C)CC1=CC(C)=CC(=O)N1O OIQJEQLSYJSNDS-UHFFFAOYSA-N 0.000 claims description 4
- 229950001046 piroctone Drugs 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 239000011347 resin Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 claims description 3
- 206010020649 Hyperkeratosis Diseases 0.000 claims description 3
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- UTOVMEACOLCUCK-PLNGDYQASA-N butyl maleate Chemical compound CCCCOC(=O)\C=C/C(O)=O UTOVMEACOLCUCK-PLNGDYQASA-N 0.000 claims description 3
- 229960004022 clotrimazole Drugs 0.000 claims description 3
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 claims description 3
- 229960000729 cyclandelate Drugs 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 229960002509 miconazole Drugs 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 229920002037 poly(vinyl butyral) polymer Polymers 0.000 claims description 3
- 229960003401 ramipril Drugs 0.000 claims description 3
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 claims description 3
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 claims description 3
- 229960001722 verapamil Drugs 0.000 claims description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims description 2
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 claims description 2
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 claims description 2
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- MPIPASJGOJYODL-SFHVURJKSA-N (R)-isoconazole Chemical compound ClC1=CC(Cl)=CC=C1[C@@H](OCC=1C(=CC=CC=1Cl)Cl)CN1C=NC=C1 MPIPASJGOJYODL-SFHVURJKSA-N 0.000 claims description 2
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 claims description 2
- ZCJYUTQZBAIHBS-UHFFFAOYSA-N 1-[2-(2,4-dichlorophenyl)-2-{[4-(phenylsulfanyl)benzyl]oxy}ethyl]imidazole Chemical compound ClC1=CC(Cl)=CC=C1C(OCC=1C=CC(SC=2C=CC=CC=2)=CC=1)CN1C=NC=C1 ZCJYUTQZBAIHBS-UHFFFAOYSA-N 0.000 claims description 2
- OCAPBUJLXMYKEJ-UHFFFAOYSA-N 1-[biphenyl-4-yl(phenyl)methyl]imidazole Chemical compound C1=NC=CN1C(C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 OCAPBUJLXMYKEJ-UHFFFAOYSA-N 0.000 claims description 2
- QXHHHPZILQDDPS-UHFFFAOYSA-N 1-{2-[(2-chloro-3-thienyl)methoxy]-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound S1C=CC(COC(CN2C=NC=C2)C=2C(=CC(Cl)=CC=2)Cl)=C1Cl QXHHHPZILQDDPS-UHFFFAOYSA-N 0.000 claims description 2
- NMKSAYKQLCHXDK-UHFFFAOYSA-N 3,3-diphenyl-N-(1-phenylethyl)-1-propanamine Chemical compound C=1C=CC=CC=1C(C)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 NMKSAYKQLCHXDK-UHFFFAOYSA-N 0.000 claims description 2
- NJXWZWXCHBNOOG-UHFFFAOYSA-N 3,3-diphenylpropyl(1-phenylethyl)azanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1C(C)[NH2+]CCC(C=1C=CC=CC=1)C1=CC=CC=C1 NJXWZWXCHBNOOG-UHFFFAOYSA-N 0.000 claims description 2
- LBSRZVRITCRLIU-UHFFFAOYSA-N 3-o-ethyl 5-o-(2-piperidin-1-ylethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCCCC2)C1C1=CC=CC([N+]([O-])=O)=C1 LBSRZVRITCRLIU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 claims description 2
- UDYUIWXQUBNDHC-UHFFFAOYSA-N 6-[[4-(4-chlorophenoxy)phenoxy]methyl]-1-hydroxy-4-methylpyridin-2-one Chemical compound ON1C(=O)C=C(C)C=C1COC(C=C1)=CC=C1OC1=CC=C(Cl)C=C1 UDYUIWXQUBNDHC-UHFFFAOYSA-N 0.000 claims description 2
- QSXXLDDWVCEBFP-UHFFFAOYSA-N 7-(ethoxymethyl)-1-(5-hydroxy-5-methylhexyl)-3-methylpurine-2,6-dione Chemical compound CN1C(=O)N(CCCCC(C)(C)O)C(=O)C2=C1N=CN2COCC QSXXLDDWVCEBFP-UHFFFAOYSA-N 0.000 claims description 2
- QOYHHIBFXOOADH-UHFFFAOYSA-N 8-[4,4-bis(4-fluorophenyl)butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 QOYHHIBFXOOADH-UHFFFAOYSA-N 0.000 claims description 2
- 208000003643 Callosities Diseases 0.000 claims description 2
- WHPAGCJNPTUGGD-UHFFFAOYSA-N Croconazole Chemical compound ClC1=CC=CC(COC=2C(=CC=CC=2)C(=C)N2C=NC=C2)=C1 WHPAGCJNPTUGGD-UHFFFAOYSA-N 0.000 claims description 2
- XQLWNAFCTODIRK-UHFFFAOYSA-N Gallopamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC(OC)=C(OC)C(OC)=C1 XQLWNAFCTODIRK-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 108010007859 Lisinopril Proteins 0.000 claims description 2
- YSEXMKHXIOCEJA-FVFQAYNVSA-N Nicergoline Chemical compound C([C@@H]1C[C@]2([C@H](N(C)C1)CC=1C3=C2C=CC=C3N(C)C=1)OC)OC(=O)C1=CN=CC(Br)=C1 YSEXMKHXIOCEJA-FVFQAYNVSA-N 0.000 claims description 2
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 claims description 2
- CANCCLAKQQHLNK-LSDHHAIUSA-N O-[[(1R,8S)-4-tricyclo[6.2.1.02,7]undeca-2(7),3,5-trienyl]] N-methyl-N-(3-methylphenyl)carbamothioate Chemical compound CN(C(=S)Oc1ccc2[C@H]3CC[C@H](C3)c2c1)c1cccc(C)c1 CANCCLAKQQHLNK-LSDHHAIUSA-N 0.000 claims description 2
- RBQOQRRFDPXAGN-UHFFFAOYSA-N Propentofylline Chemical compound CN1C(=O)N(CCCCC(C)=O)C(=O)C2=C1N=CN2CCC RBQOQRRFDPXAGN-UHFFFAOYSA-N 0.000 claims description 2
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 claims description 2
- 229960000528 amlodipine Drugs 0.000 claims description 2
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004069 aziridinyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 229960000830 captopril Drugs 0.000 claims description 2
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 claims description 2
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- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 2
- 229960004042 diazoxide Drugs 0.000 claims description 2
- VQKLRVZQQYVIJW-UHFFFAOYSA-N dihydralazine Chemical compound C1=CC=C2C(NN)=NN=C(NN)C2=C1 VQKLRVZQQYVIJW-UHFFFAOYSA-N 0.000 claims description 2
- 229960002877 dihydralazine Drugs 0.000 claims description 2
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- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 claims description 2
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- 238000004090 dissolution Methods 0.000 claims description 2
- ITAMRBIZWGDOHW-UHFFFAOYSA-N fantofarone Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCOC1=CC=C(S(=O)(=O)C2=C3C=CC=CN3C=C2C(C)C)C=C1 ITAMRBIZWGDOHW-UHFFFAOYSA-N 0.000 claims description 2
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- SMANXXCATUTDDT-QPJJXVBHSA-N flunarizine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCN(C\C=C\C=2C=CC=CC=2)CC1 SMANXXCATUTDDT-QPJJXVBHSA-N 0.000 claims description 2
- 229960000326 flunarizine Drugs 0.000 claims description 2
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- 239000003205 fragrance Substances 0.000 claims description 2
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- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
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- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 2
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 claims description 2
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- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 claims description 2
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- FUSNMLFNXJSCDI-UHFFFAOYSA-N tolnaftate Chemical compound C=1C=C2C=CC=CC2=CC=1OC(=S)N(C)C1=CC=CC(C)=C1 FUSNMLFNXJSCDI-UHFFFAOYSA-N 0.000 claims description 2
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- IIUZTXTZRGLYTI-UHFFFAOYSA-N Dihydrogriseofulvin Natural products COC1CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 IIUZTXTZRGLYTI-UHFFFAOYSA-N 0.000 claims 1
- UXWOXTQWVMFRSE-UHFFFAOYSA-N Griseoviridin Natural products O=C1OC(C)CC=C(C(NCC=CC=CC(O)CC(O)C2)=O)SCC1NC(=O)C1=COC2=N1 UXWOXTQWVMFRSE-UHFFFAOYSA-N 0.000 claims 1
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
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Abstract
一种包含具有血管扩张作用的化合物和水不溶性膜形成剂的指甲油适合于治疗指甲的生长障碍。
Description
本发明涉及包含促进指甲生长的化合物和水不溶性成膜剂的指甲油,涉及其制备方法和其于治疗指甲生长障碍的用途。
封闭并且保护指甲的指甲体为指尖或脚指失的皮肤的一个角质的坚硬附件,其由在手指或脚指的背面的表皮层的一个口袋状套叠长出。
指甲体的指甲材料的形成主要在甲床(占据从其近侧端直到弧影的指甲窦的较低部分的特殊化的组织)进行。甲床区域向远侧端与指甲床相邻,因此指甲体,其在其下表面上呈纵向长条结构形式,坚固粘附于甲下表皮。甲下表皮为在甲床和手指垫之间的表皮层的背侧区域。
指甲体的表面是平滑的,且它的颜色由于corial毛细管结果而呈现细致优雅的粉红色。只有存在于近侧端的1-5毫米大小的半月形孤影区域看起来是发白的。
指甲体的生长速率,也就是它超过自由的边缘的延长,取决于甲床里的指甲细胞再生的程度。从其形成的细胞物质分化成片状角质结构而被动地推向远侧端方向。
指甲在整个生命过程中不断地生长。生长速率随年龄减少。平均每周的增加长度手指甲为0.5到1.2毫米,且除年龄和性别之外,血液循环,日常饮食和生理上压力会对此值具有影响性。在工作手上的指甲被认为生长较快。脚趾甲显著慢于手指甲,尤其在比较年长的人的情况下。
在某些约35岁的人的正常指甲生长速率的情况,新手指甲生长的所需时间为约6个月,和脚趾甲再生约需12个月。
除导致指甲生长的缺乏的体质因素,很多局部或一般的疾病进展之外,毒物,医药,化学品和创伤也可不利地影响指甲生长和外观。
指甲生长在甲癣(onychomycoses)的治疗和治疗必需的期间扮演非常决定性的角色;甲癣意为由真菌引起的甲床感染和,随感病时间的增加,可延伸遍及整个指甲,包括指甲体的看得见部分。
在远侧端甲下甲癣的情况中,最常观察到临床的类型中,病原通过首先获得进入甲下角层攻击指甲器官。当感染进一步发展,指甲体的下侧亦被感染。在以后的阶段中,指甲体发生变色和更改结构,结果指甲的外观完全地改变。Keratophilic真菌例如红色发癣菌(Trichophytonrubrum)或发疮小芽孢癣菌(T.mentagrophytes)以相当特定的方式改变指甲体。他们导至看得见的变色,其通过进行阶段中破坏指甲体的薄片状结构而完成和最后导至保护屏障的完全破坏。当感染继续时,甲下表皮和甲床的甲下组织碎片是进一步的微生物的理想培养地,其又有助于指甲体下侧的化学和物理性质额外变化。最后甲体与甲床分开,当移动时,其带给病人极大痛苦。那些影响可由于真菌的作用而因此损失整个指甲体,所以只有角化过度甲床保留,其因此未给予抗外部影响力的保护。现在直接移动是非常不可能的,因为缺乏起挢台作用的指甲体。
感染蔓延的速率各情形不同。其一方面视指向甲床的方向由指甲自由端穿入微生物的生长速率而定,和另一方面由指向指甲自由端的方向的甲床指甲的生长速率而定。
只有健康的指甲以其生长速率为基础,抗自指甲自由端的微生物的穿入而被保护。然而,如果指甲生长因为年龄或疾病而进行较慢,如果未治疗的话,那些微生物可蔓延而未受阻碍。
一种已知的甲癣的治疗目前为害病指甲的局部治疗,其使用具有抗真菌作用的指甲油配剂,有时与具有全身作用的抗真菌剂组合使用。此治疗方法的一个缺点为是该治疗必须施予相当长的时间直到害病的指甲已经临床地痊愈,也就是直到受感染的指甲区域已经生长出来,而且新指甲已清楚地再生。这导致治疗(通常花几个月的治疗)通常不被病人所坚持,且造成治疗失败。通常使用的局部/全身的组合治疗也存在相当的成本问题,这是由全身性抗真菌剂的价格造成的。
现已发现如果将根据本发明的配剂涂至指甲上,特别是害病的指甲,指甲的生长可被加速。这些配剂不但适于作为在甲癣的特殊治疗期间用于加速生长的额外辅助措施,且也可用作为治疗不同原因的指甲生长障碍。
本发明因此涉及一种包含水不溶性成膜剂和至少一种血管扩张作用的化合物的指甲油。
具有血管扩张作用的化合物为,例如,
其中R1和R2彼此独立为
1)氢原子,
2)(C1-C8)-烷基,
3)(C2-C8)-烯基,
4)苯基-(C1-C8)-烷基,
5)萘基-(C1-C4)-烷基或
6)(C3-C8)-环烷基,或
7)R1和R2和N原子一起形成由下列基团所组成的杂环
7.1吖丙啶基,
7.2氮杂环丁烯基,
7.3吡咯烷基,
7.4哌啶基,
7.5六氢氮杂基,
7.6七甲基亚氨基,
7.7八甲基亚氨基,
7.8吗啉基或
7.9 4-(C1-C4)-烷基-哌嗪基,或
8)来自7)的基团,其中杂环基的碳原子被1至3个(C1-C4)
-烷基取代,
R3为1)氢原子,
2)(C1-C8)-烷基,
3)(C2-C8)-烯基,
4)苯基-(C1-C8)-烷基,
5)萘基-(C1-C8)-烷基,
6)苄基,
7)苯基,
8)萘基,
9)(C3-C8)-环烷基或
10)(C1-C6)-烷基,其被卤素单或多取代,和
A1,A2和A3各自独立为氢原子或乙酰基。
优选的式Ⅰ化合物为其中
R1和R2和N原子一起形成杂环哌啶基,
R3为氢原子和
A1,A2和A3各自独立为氢原子或乙酰基者。
特别优选的式Ⅰ化合物为其中
R1和R2和N原子一起形成杂环哌啶基和
R3,A1,A2和A3为氢原子者。
2.诸如双胼酞嗪(dihydralazine),二异丙基胺或重氮氧化物(diazoxide)的化合物。
3.钙拮抗剂,例如硝苯吡啶(nifedipine),尼卡地平(nicardipine),凡拉帕密尔(verapamil),代尔泰兰(diltiazem),尼索尔地平(nisoldipine),尼特地平(nitrendipine),尼宛地平(nivaldipine),艾斯拉地平(isradipine),芬罗地平(felodipine),尼慕地平(nimodipin),葛罗帕密尔(gallopamil),苯乙二苯丙胺(fendiline),氟苯桂嗪(flunarizine)或安罗地平(amlodipine),帝婆地平(diperdipine),福拉斯吡立乐(fluspirilene),普立莫德(primozide),发托发罗(fantofarone),尼色够力(nicergoline),或环扁桃酯(clycandelate)。
4.血管紧张素转换酶抑制剂,例如昆那普立尔(quinapril),立斯诺普立尔(lisinopril),贝那端立尔(benzazepril),卡普托普立尔(captopril),拉密普立尔(ramipril),弗斯诺普立尔(fosinopril),西发拉普立尔(cifazapril)或他拉多普立尔(trandolapril)。
5.甲基黄嘌呤化合物,例如己酮可可碱(pentoxifylline),普罗配托非立(propentofylline),托尔巴非立(torbafylline)。
6.促进头发生长的化合物,例如如EP0427625所描述的2,4-二氨基-6-烷氧基-3-磺酰氧基(sulfoxy)嘧啶氢氧化物内盐,其中在烷氧基中具有1到6个碳原子,或如WO9221317所描述的2,4-二氨基-6-丁氧基-3-磺酰氧基嘧啶氢氧化物内盐,吡啶-1-氧化物衍生物或2,6-二氨基-4-哌啶子基吡啶;描述于WO9119701的2,6-二氨基-1,3,5-三嗪衍生物或2,6-二氨基-4-丁氧基-1,3,5-三嗪1-氧化物。
式Ⅰ的化合物如美国专利第3,461,461号所描述制备。
使用根据本发明的指甲油作为额外的加速生长的辅助措施,甲癣的特殊治疗的治疗时间可明显减短,其除对治疗成本最优化之外,也提供改进的病人的顺从性。鉴于以下事实,这是一非常重要的发现:由于目前为止差的治疗经验而造成病人缺乏顺从性,其原因是不能看到很快的痊愈。
所存在的水不溶性油膜在配剂干燥之后也具有超越亲水性系统的优点:其在洗涤、沐浴或淋浴期间不会从指甲表面除去,也就是不须在这之后再一次涂敷。其也避免在以水处理期间已渗透至指甲的活性化合物再一次被溶解出来。
对于早期阶段的远侧端甲下甲癣的治疗,使用根据本发明的指甲油而无需附加特殊抗真菌治疗也是可能的。
使用根据本发明的指甲油不仅仅限制于在甲癣治疗期间的治疗或辅助措施。根据本发明的指甲油也可用于各种不同其他起源的指甲生长障碍的治疗。
在根据本发明指甲油中的活性化合物的含量因各活性化合物的结构而定,并因此决定于其从油膜的释放和其在指甲中的渗透性质。
根据本发明的指甲油,也就是包含溶剂的使用形式,通常包含0.1到10,优选2至5重量%的量的活性化合物。
除溶解在溶剂或溶剂混合物的活性化合物外,根据本发明的指甲油也包含作为必需成份的一种或多种在配剂干燥之后于指甲上形成水不溶性膜的成膜剂。
适当的成膜剂为,例如,基于硝酸纤维素的物质或生理上可接受的聚合物,例如习用于化妆品中的聚合物,较佳为与硝酸纤维素的混合物。可提及的实例为聚乙酸乙烯酯和部分水解的聚乙酸乙烯酯,乙酸乙烯酯(一方面)与丙烯酸或巴豆酸或马来酸单烷基酯(另一方面)的共聚物,乙酸乙烯酯(一方面)和巴豆酸和新癸酸乙烯基酯,或巴豆酸和丙酸乙烯酯(另一方面)的三元共聚物,甲基乙烯基醚和顺丁烯二酸单烷基酯(特别是顺丁烯二酸单丁基酯)的共聚物,脂肪酸乙烯基酯和丙烯酸或甲基丙烯酸的共聚物,N-乙烯基吡咯烷酮、甲基丙烯酸和甲基丙烯酸烷基酯的共聚物,丙烯酸和甲基丙烯酸或丙烯酸烷基酯或甲基丙烯酸烷基酯的共聚物,特别是含有季铵基团的共聚物,或包括丙烯酸乙酯,甲基丙烯酸甲酯或甲基丙烯酸三甲胺乙酯氯化物(Trimethylammonioethylmethacrylat-chlorid)的聚合物,共聚物或混合物,或聚乙烯醇缩乙醛和聚乙烯醇缩丁醛,烷基取代了的聚-N-乙烯基吡咯烷酮,烯烃和顺丁烯二酸酐的共聚物的烷基酯,和松脂和丙烯酸的反应产物。在这些酯中,烷基通常为短链且在大部分的情形下没有超过四个碳原子。
可能的生理上可接受的溶剂为例如习用于化妆品的烃类、卤代烃类、醇类、醚类、酮类和酯类的物质,特别是一元醇的乙酸酯类,例如乙酸乙酯和乙酸丁酯,如果适当的话与芳香烃类,例如甲苯和/或醇,例如乙醇或异丙醇混合。
溶剂的组合已知为指甲油或指甲油膜的干燥时间、涂刷性和其他重要性质的决定要素。溶剂系统优选包含低沸点成分(=具有100℃沸点的溶剂)和中等沸点成份(=具有高至150℃沸点的溶剂)的优化混合物,如果适当的话含有小含量高沸点成分(=具有高至200℃沸点的溶剂)。
此外根据本发明的指甲油可包含习用于化妆品的添加剂,例如以邻苯二甲酸盐,三乙酸甘油基酯或樟脑为基的软化剂、染料或着色颜料、珠光剂、延迟沉淀的试剂、磺酰胺树脂、硅酸盐、芳香物质,湿润剂,例如二辛基磺基-琥珀酸钠、羊毛脂衍生物、光保护剂,例如2-羟基-4-甲氧基苯酮、抗菌活性的物质和具有角质层分离和/或皮肤角质新生作用的物质,例如亚硫酸铵、和氢硫基醋酸、尿素、尿囊素、酶和水杨酸的酯和盐。
着色或涂色指甲油具有优点,例如,采用根据本发明的配剂可适合病人的美感,和现在已存在的指甲变化对其他人不是直接看得见的。
根据本发明制备指甲油的方法包括混合溶解形式的水不溶性成膜剂,与一种或多种活性化合物和,如果必需的话,进一步的加工配剂。
本发明此外涉及一种指甲油,其包括
1.水不溶性成膜剂,
2.血管扩张的化合物和
3.具有局部作用的抗真菌剂。
具有局部作用的抗真菌剂为羟基吡啶酮类,例如:环己吡酮氨乙醇(ciclopirox),吡罗克酮(piroctone)或立罗吡罗(rilopirox),吗啉衍生物,例如安莫罗芬(amorofine),唑类(azole),例如必唑(Bifonazol),克霉唑(clotrimazol),氯苯甲氧咪唑(econazole),麦克唑(miconazole),欧西克唑(oxiconazole),克酮唑(croconazole),芬泰康唑(fenticonazole),泰克唑(tioconazole),酮克唑(ketoconazole)或异克唑(isoconazole),或烯丙基化合物,例如特必那芬(terbinafin)或那福替芬(naftifin),灰黄微素(Griseofuvin),托希拉特(tolciclate),托那福特(tolnaftate)或布特那芬(butenafin)作为抗真菌剂。
可进一步提及的适当羟基吡啶酮为,例如:1-羟基-4-甲基-6-正己基-6-异己基-,-6-正-庚基-或-6-异庚基-2-吡啶酮,1-羟基-4-甲基-6-辛基或-6-异辛基-2-吡啶酮,和特别是1-羟基-4-甲基-6-(2,4,4-三甲基戊基)-2-吡啶酮,1-羟基-4-甲基-6-环己基-2-吡啶酮,1-羟基-4-甲基-6-环己甲基或6-环己乙基-2-吡啶酮,其中环己基在各情况也可携带一甲基,1-羟基-4-甲基-6-(2-双环〔2.2.1〕庚基)-2-吡啶酮,1-羟基-3,4-二甲基-6-苄基-或-6-二甲苄基-2-吡啶酮和1-羟基-4-甲基-6-(β-苯乙基)-2-吡啶酮。
水不溶性成膜剂、血管扩张化合物、溶剂和进一步的添加剂的含量符合上述不含抗真菌剂的指甲油中的含量。
在根据本发明的指甲油中具有局部作用的抗真菌剂视特定的抗真菌剂的结构和其从指甲油膜中的释放、其在指甲中的渗透性质和其抗微生物性质而定。
根据本发明的指甲油(包含溶剂的使用形式),一般包括0.5到20,优选2到15重量%(重量%)的量的具有局部作用的抗真菌剂。在用于治疗真菌病(mycoses)的医药指甲油中的最小含量为4重量%;用于预防的指甲油包含少于4和至少1重量%的抗真菌剂。在各情况中基于非挥发性成份的量,也就是成膜剂、血管扩张化合物、任何存在的颜料、软化剂和其他非挥发性的添加剂及具有局部作用的抗真菌剂的总量,根据本发明的指甲油一般包含在2到80,较佳10到60,和特别是20到40重量%的量的抗真菌剂。
此外本发明涉及根据本发明的指甲油配剂在制备用于治疗指甲的生长障碍的药物中的用途。
实施例1
根据本发明的配剂具有下列组成:
6-氨基-4-哌啶子基-
1,2-二氢-1-羟基-2-亚氨基嘧啶 2.5%
丙烯酸乙酯/甲基丙烯酸甲酯/
甲基丙烯酸三甲胺乙基酯氯化物,
1∶2∶0.2的摩尔比(参考Uberzogene
Arzneiformen[膜衣的药物形式],作
者Bauer,Lehmann,Osterwald和Rot-
hgang,第239-242页,Wiss.Verlag-
sgesellschaft mbH,Stuttgart,1988
;EUDRAGITRL 100) 7.0%
乙醇96% 75.0%
乙酸乙酯 10.5%
乙酸丁酯 5.0%
百分比量以重量为基础表示。
指甲油是通过将各种不同的成分溶解于溶剂中制得。
根据本发明配剂的作用通过在牛的角质薄层的渗透测试和在目标上的治疗测试而证实。在牛的角质薄层的渗透测试允许活性化合物从特殊配剂中释放出和随后渗透通过待测试的角蛋白材料。
作为对照实施例,
6-氨基-4-哌啶子基-1,2-二氢-1-
羟基-2-亚氨基嘧啶 2.5%
溶解在乙醇96% 97.5%
A)在牛角质薄层的渗透测试
活性化合物的渗透作用通过时间分辨的傅立叶变换红外线光谱测量(参考Th.M.Bayerl等人;皮肤研究杂志(J.Invest.Dermatol.)105:291-295,1995)ATR技术进行:
100μl的测试配剂(根据本发明的配剂或对照实施例)涂敷至0.5毫米厚的牛角质薄层上。牛角质薄层以其下侧固定至硅晶体上侧。在活性化合物渗透过牛角质薄层之后,物质的FI-IR光谱赖于存在的活性化合物的浓度而受影响,所以在活性化合物(其呈时间的函数渗透)的量上的定量结论可通过与直接地涂敷到测量晶体上的测试配剂比较测量而获得。
这些实验表示,根据本发明的指甲油配剂显示活性化合物经过角蛋白材料的渗透速率大于对照实施例十倍。这是一令人惊讶的发现,因为不会预料到,来自指甲油配剂干燥之后的水不溶性固体体系中的活性化合物的生物利用率比来自乙醇溶液的活性化合物的生物利用率更好。
B)活性试验
根据本发明指甲油配剂的促进指甲生长的性质是在2人身上进行测试。在每种情况下另一只手或另一只脚的未处理的手指和脚趾甲作为生长的直接比较。为了研究或者排除(特别是在手上)因为在工作手上的指甲由于其中占优势的指甲器官的较好循环可能较快的生长而引入的误差,将一个测试者的工作手的手指和另一个测试者的非工作手的手指甲用测试配剂处理。因此在一测试者的右工作手的指甲和左脚的指甲上用测试物质处理,同时在另一测试者身上进行成镜象的配剂施用。
为了决定生长速率,所有指甲的长度使用精密滑轨测定,测量的最近出发点在孤影的顶点,因为此点表示固定点。选择指甲的边缘当做远侧端界限。
结果:(治疗指甲相对于未治疗指甲的生长长度的增加;治疗时间4星期每日一次)手指甲治疗工作手 +45.3%治疗非工作手 +18.6%脚趾甲治疗左脚 +27.6%治疗右脚 +23.9%
除生长长度的增加之外,指甲的生长面积的增加经由透明毫米膜测定。
结果:(治疗指甲相对于未治疗指甲的生长面积的增加;治疗时间4星期每日一次)
手指甲治疗工作手 +53.3%治疗非工作手 +45.7%脚趾甲治疗左脚 +110.8%治疗右脚 +177.5%实施例3
根据本发明的配剂具有下列组成:6-氨基-4-哌啶子基-1,2-二氢-1-羟基-2-亚氨基嘧啶 2.0%4-[3-〔对-(1,1-二甲丙基)苯基]-2-甲基-丙基〕-2,6-二甲基-吗啉盐酸盐 5.0%EUDRAGITRL 100 10.0%乙醇96% 73.0%乙酸乙酯 10.0%
实施例4
根据本发明的配剂具有下列组成:4-氨基-4-哌啶子基-1,2-二氢-1-羟基-2-亚氨基嘧啶 2.5%1-羟基-4-甲基-6-环己基-2-吡啶酮 8.0%在异丙醇中的甲基乙烯醚和顺丁烯二酸单丁基酯的共聚物的50%强度溶液 35.0%乙醇96% 44.5%乙酸乙酯 10.0%
实施例5
根据本发明的配剂具有下列组成:5-[(3,4-二甲氧基苯乙基)甲氨基] 2.0%2-(3,4-二甲氧基苯基)-2-异丙基戊腈盐酸盐(凡拉帕密尔(verapamil)盐酸盐)1-[2,4-二氯-β-(2,4-二氯苄氧基)苯乙基]嘧唑(miconazole) 2.0%聚乙烯醇缩丁醛 3.8%硝酸纤维素 3.1%邻苯二甲酸二丁酯 0.6%乙酸乙酯 10.0%乙醇96% 78.5%
实施例6
根据本发明的配剂具有下列组成:与烯丙基抗真菌剂(2S,3aS,6aS)-1-[(S)-N-[(S)-1-乙氧羰基-3-苯丙基]丙氨酰基]-八氢环戊二烯并[b]吡咯-2-羧酸(拉密普立尔(ramipril))组合的血管紧张素转换酶抑制剂 2.0%(E)-N-(6,6-二甲基-2-庚烯-4-炔基)-N-甲基-萘甲胺(托尔巴非立(terbinafin)) 0.5%甲基丙烯酸/丙烯酸乙酯1∶1共聚物 6.5%乙醇96% 71.0%乙酸乙酯 20.0%
Claims (10)
1.一种指甲油,其包含水不溶性成膜剂和具有血管扩张作用的化合物。
2.如权利要求1的指甲油,其中作为具有血管扩张作用的化合物系采用式(Ⅰ)化合物
其中R1和R2彼此独立为
1)氢原子,
2)(C1-C8)-烷基,
3)(C2-C8)-烯基,
4)苯基-(C1-C8)-烷基,
5)萘基-(C1-C4)-烷基或
6)(C3-C8)-环烷基,或
7)R1和R2和N原子一起形成由下列基团所组成的杂环
7.1吖丙啶基,
7.2氮杂环丁烯基,
7.3吡咯烷基,
7.4哌啶基,
7.5六氢氮杂基,
7.6七甲基亚氨基,
7.7八甲基亚氨基,
7.8吗啉基或
7.9 4-(C1-C4)-烷基-哌嗪基,或
8)来自7)的基团,其中杂环基的碳原子被1至3个(C1-C4)-烷基取代,
R3为 1)氢原子,
2)(C1-C8)-烷基,
3)(C2-C8)-烯基,
4)苯基-(C1-C8)-烷基,
5)萘基-(C1-C8)-烷基,
6)苄基,
7)苯基,
8)萘基,
9)(C3-C8)-环烷基或
10)(C1-C6)-烷基,其被卤素单或多取代,和
A1,A2和A3各自独立为氢原子或乙酰基,或
双胼酞嗪(dihydralazine),二异丙基胺,重氮氧化物(diazoxide)或硝苯吡啶(nifedipine),尼卡地平(nicardipine),凡拉帕密尔(verapamil),代尔泰兰(diltiazem),尼索尔地平(nisoldipine),尼特地平(nitrendipine),尼宛地平(nivaldipine),艾斯拉地平(isradipine),芬罗地平(felodipine),尼慕地平(nimodipin),葛罗帕密尔(gallopamil),苯乙二苯丙胺(fendiline),氟苯桂嗪(flunarizine)或安罗地平(amlodipine),帝婆地平(diperdipine),福拉斯吡立乐(fluspirilene),普立莫德(primozide),发托发罗(fantofarone),尼色够力(nicergoline),环扁桃酯(cyclandelate),或昆那普立尔(quinapril),立斯诺普立尔(lisinopril),贝那端立尔(benzazepril),卡普托普立尔(captopril),拉密普立尔(ramipril),弗斯诺普立尔(fosinopril),西发拉普立尔(cifazapril),他拉多普立尔(trandolapril),己酮可可碱(pentoxifylline),普罗配托非立(propentofylline),托尔巴非立(torbafylline),2,4-二氨基-6-丁氧基-3-磺酰氧基嘧啶氢氧化物内盐,2,6-二氨基-4-哌啶子基吡啶,2,6-二氨基-4-丁氧基-1,3,5-三嗪-1-氧化物或其混合物。
3.如权利要求2的指甲油,其中系采用6-氨基-4-哌啶子基-1,2-二氢-1-羟基-2-亚氨基嘧啶作为具有血管扩张作用的化合物。
4.如权利要求第1或2项的指甲油,其中系采用丙烯酸乙酯/甲基丙烯酸甲酯/甲基丙烯酸三甲基胺乙酯氯化物的共聚物,甲基乙烯基醚和马来酸单丁酯的共聚物,聚乙烯醇缩丁醛和硝酸纤维素聚合物或甲基丙烯酸和丙烯酸乙酯的共聚物作为水不溶性成膜剂。
5.如权利要求第1项的指甲油,其中含有0.1到10重量百分比,优选2至5重量百分比的具有血管扩张作用的化合物。
6.如权利要求1-5中一项或多项的指甲油,其中另外包含具有局部作用的抗真菌剂。
7.如权利要求第6项的指甲油,其中包含羟基吡啶酮,例如环己吡酮氨乙醇(ciclopirox),吡罗克酮(piroctone)或立罗吡罗(rilopirox),吗啉衍生物,例如安莫罗芬(amorofine),唑类,例如必唑(bifonazole),克霉唑(clotrimazole),氯苯甲氧咪唑(econazole),麦克唑(miconazole),欧西克唑(oxiconazole),克酮唑(croconazole),芬泰康唑(fenticonazole),泰克唑(tioconazole),酮克唑(ketoconazole)或异克唑(isoconazole),或烯丙基化合物,例如特必那芬(terbinafin)或那福替芬(naftifin),灰黄微素(Griseofulvin),托希拉特(tolciclate),托那福特(tolnaftate)或布特那芬(butenafin)作为具有局部作用的抗真菌剂。
8.如权利要求第6或第7项的指甲油,其中含有0.5到20重量百分比,优选2至5重量百分比具有局部作用的抗真菌剂。
9.一种制备如权利要求第1至8项中一或多项的指甲油的方法,其包括混合溶解形式的水不溶性成膜剂与具有血管扩张作用的化合物和,如果适当的话,加入具有局部作用的抗真菌剂和其他添加剂。
10.如权利要求第1到8项中一或多项的指甲油的应用,用于制备治疗指甲的生长障碍的药物。
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DE19604190.2 | 1996-02-06 | ||
DE19604190A DE19604190A1 (de) | 1996-02-06 | 1996-02-06 | Nagelwachstumsfördernde Zubereitungen |
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US (1) | US6007798A (zh) |
EP (1) | EP0879052B1 (zh) |
JP (1) | JP4119480B2 (zh) |
KR (1) | KR100457849B1 (zh) |
CN (1) | CN1239157C (zh) |
AT (1) | ATE198155T1 (zh) |
AU (1) | AU706531B2 (zh) |
BG (1) | BG63485B1 (zh) |
BR (1) | BR9707353A (zh) |
CA (1) | CA2245693C (zh) |
CZ (1) | CZ290231B6 (zh) |
DE (2) | DE19604190A1 (zh) |
DK (1) | DK0879052T3 (zh) |
ES (1) | ES2154021T3 (zh) |
GR (1) | GR3035085T3 (zh) |
HK (1) | HK1018398A1 (zh) |
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Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6231875B1 (en) | 1998-03-31 | 2001-05-15 | Johnson & Johnson Consumer Companies, Inc. | Acidified composition for topical treatment of nail and skin conditions |
US6143794A (en) * | 1998-04-17 | 2000-11-07 | Bertek Pharmaceuticals, Inc. | Topical formulations for the treatment of nail fungal diseases |
DE10011081A1 (de) * | 2000-03-09 | 2001-09-13 | Aventis Pharma Gmbh | Antiinfektive Wirkstoffkombinationen und ihre Verwendung zur topischen Behandlung von Pilzerkrankungen der Fuß- und Fingernägel |
US7074392B1 (en) | 2000-03-27 | 2006-07-11 | Taro Pharmaceutical Industries Limited | Controllled delivery system of antifungal and keratolytic agents for local treatment of fungal infections |
US8257688B2 (en) * | 2000-03-27 | 2012-09-04 | Taro Pharmaceuticals Industries | Controlled delivery system of antifungal and keratolytic agents for local treatment of fungal infections of the nail and surrounding tissues |
US20030049307A1 (en) * | 2002-08-15 | 2003-03-13 | Gyurik Robert J. | Pharmaceutical composition |
US20040147534A1 (en) * | 2003-01-23 | 2004-07-29 | Foote Mary Ann | Topical composition and method for treating occlusive wounds |
WO2005072696A1 (en) * | 2004-01-30 | 2005-08-11 | Ace Aps | Use of ace inhibitors and/or angiotensin ii receptor antagonists for the improving and/or maintaining the skin tone and for the treatment of skin ageing |
ZA200702216B (en) * | 2004-08-18 | 2008-11-26 | Ace Aps | Cosmetic and pharmaceutical compositions comprising ACE inhibitors and/or angiotensin II receptor antagonists |
US7531058B2 (en) * | 2005-02-24 | 2009-05-12 | The Boeing Company | Reinforced rampdown for composite structural member and method for same |
US20060251593A1 (en) * | 2005-04-07 | 2006-11-09 | Work By Docs, Inc. | Colored nail enamel treatment |
US20080153122A1 (en) * | 2006-12-21 | 2008-06-26 | Susan Beth Cantor | Method and system for enhancing self-treatment of onychomycosis |
US8470802B2 (en) | 2008-10-08 | 2013-06-25 | Conopco, Inc. | Sensory modifier |
US8865678B2 (en) | 2008-10-08 | 2014-10-21 | Conopco, Inc. | Universal sensory structurant |
SG10201604682VA (en) | 2011-06-10 | 2016-07-28 | Merck Patent Gmbh | Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity |
CA2851243A1 (en) * | 2011-10-05 | 2013-04-11 | Allergan, Inc. | Compositions for enhancing nail health |
US8697753B1 (en) | 2013-02-07 | 2014-04-15 | Polichem Sa | Method of treating onychomycosis |
RU2601896C2 (ru) * | 2013-04-30 | 2016-11-10 | Закрытое Акционерное Общество "Вертекс" | Комбинированный препарат для лечения грибковых заболеваний ногтей |
Family Cites Families (6)
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ATE84208T1 (de) * | 1985-11-04 | 1993-01-15 | Owen Galderma Lab Inc | Filmbildende arzneimitteltraeger zur verabreichung von arzneimitteln an naegeln; verfahren zur verwendung. |
DE3544983A1 (de) * | 1985-12-19 | 1987-06-25 | Hoechst Ag | Antimykotisch wirksamer nagellack |
US4950475A (en) * | 1988-07-19 | 1990-08-21 | Imaginative Research Associates, Inc. | Novel film-forming gels with high concentrations of humectants and emollients |
US4927626A (en) * | 1988-10-28 | 1990-05-22 | Devillez Richard L | Method for enhancement of unguis growth |
FR2689008A1 (fr) * | 1992-03-31 | 1993-10-01 | Louis Benelli | Compositions efficaces notamment contre la chute des cheveux et pour favoriser leur régénération ainsi que celle des ongles. |
GB9404293D0 (en) * | 1994-03-04 | 1994-04-20 | Shuster Sam | Drug delivery system |
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