MXPA00002847A - Reduction of hair growth - Google Patents
Reduction of hair growthInfo
- Publication number
- MXPA00002847A MXPA00002847A MXPA/A/2000/002847A MXPA00002847A MXPA00002847A MX PA00002847 A MXPA00002847 A MX PA00002847A MX PA00002847 A MXPA00002847 A MX PA00002847A MX PA00002847 A MXPA00002847 A MX PA00002847A
- Authority
- MX
- Mexico
- Prior art keywords
- aminoacyl
- inhibitor
- trna synthetase
- hair growth
- amino
- Prior art date
Links
- 230000003698 anagen phase Effects 0.000 title claims abstract description 34
- 230000003779 hair growth Effects 0.000 title claims abstract description 34
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 72
- 239000003112 inhibitor Substances 0.000 claims abstract description 67
- 102000008745 EC 6.1.1.- Human genes 0.000 claims abstract description 56
- 108030004302 EC 6.1.1.- Proteins 0.000 claims abstract description 56
- 210000003491 Skin Anatomy 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims description 27
- 150000001413 amino acids Chemical class 0.000 claims description 18
- 229920001949 Transfer RNA Polymers 0.000 claims description 11
- 241000282414 Homo sapiens Species 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 8
- 238000004166 bioassay Methods 0.000 claims description 7
- 239000000969 carrier Substances 0.000 claims description 7
- 241000699673 Mesocricetus auratus Species 0.000 claims description 6
- DZGWFCGJZKJUFP-UHFFFAOYSA-N Tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 claims description 6
- DLMYFMLKORXJPO-FQEVSTJZSA-N (2R)-2-amino-3-tritylsulfanylpropanoic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(SC[C@H](N)C(O)=O)C1=CC=CC=C1 DLMYFMLKORXJPO-FQEVSTJZSA-N 0.000 claims description 5
- VTQHAQXFSHDMHT-NTSWFWBYSA-N (2S,3S)-2-amino-3-methylpentan-1-ol Chemical compound CC[C@H](C)[C@H](N)CO VTQHAQXFSHDMHT-NTSWFWBYSA-N 0.000 claims description 5
- 102000003960 Ligases Human genes 0.000 claims description 5
- 108090000364 Ligases Proteins 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- -1 cyclohexyl ester Chemical class 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 230000002194 synthesizing Effects 0.000 claims description 5
- HHBTZIXDIIYQRL-UHFFFAOYSA-N 1,2-diamino-5-phenylpentan-3-ol Chemical group NCC(N)C(O)CCC1=CC=CC=C1 HHBTZIXDIIYQRL-UHFFFAOYSA-N 0.000 claims description 4
- YSMODUONRAFBET-UHFFFAOYSA-N 5-hydroxylysine Chemical compound NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 claims description 4
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 4
- APJYDQYYACXCRM-UHFFFAOYSA-N Tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 claims description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 4
- VPSSPAXIFBTOHY-LURJTMIESA-N (2S)-2-amino-4-methylpentan-1-ol Chemical compound CC(C)C[C@H](N)CO VPSSPAXIFBTOHY-LURJTMIESA-N 0.000 claims description 3
- MIQJGZAEWQQAPN-YFKPBYRVSA-N (2S)-2-amino-4-methylsulfanylbutan-1-ol Chemical compound CSCC[C@H](N)CO MIQJGZAEWQQAPN-YFKPBYRVSA-N 0.000 claims description 3
- DSLBDPPHINVUID-REOHCLBHSA-N (2S)-2-aminobutanediamide Chemical compound NC(=O)[C@@H](N)CC(N)=O DSLBDPPHINVUID-REOHCLBHSA-N 0.000 claims description 3
- OMGHIGVFLOPEHJ-UHFFFAOYSA-N 2,5-dihydro-1H-pyrrol-1-ium-2-carboxylate Chemical compound OC(=O)C1NCC=C1 OMGHIGVFLOPEHJ-UHFFFAOYSA-N 0.000 claims description 3
- KEZRWUUMKVVUPT-UHFFFAOYSA-N 2-amino-3-(dimethylazaniumyl)propanoate Chemical compound CN(C)CC(N)C(O)=O KEZRWUUMKVVUPT-UHFFFAOYSA-N 0.000 claims description 3
- WDVSHHCDHLJJJR-UHFFFAOYSA-N 3,6-diaminoacridine Chemical compound C1=CC(N)=CC2=NC3=CC(N)=CC=C3C=C21 WDVSHHCDHLJJJR-UHFFFAOYSA-N 0.000 claims description 3
- LGVJIYCMHMKTPB-UHFFFAOYSA-N 3-hydroxynorvaline Chemical compound CCC(O)C(N)C(O)=O LGVJIYCMHMKTPB-UHFFFAOYSA-N 0.000 claims description 3
- PMLJIHNCYNOQEQ-REOHCLBHSA-N L-aspartic 1-amide Chemical compound NC(=O)[C@@H](N)CC(O)=O PMLJIHNCYNOQEQ-REOHCLBHSA-N 0.000 claims description 3
- 239000004201 L-cysteine Substances 0.000 claims description 3
- NPKSPKHJBVJUKB-UHFFFAOYSA-N N-phenylglycine Chemical compound OC(=O)CNC1=CC=CC=C1 NPKSPKHJBVJUKB-UHFFFAOYSA-N 0.000 claims description 3
- 229960000286 Proflavine Drugs 0.000 claims description 3
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2S)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 claims description 3
- 239000003098 androgen Substances 0.000 claims description 3
- PMMYEEVYMWASQN-IMJSIDKUSA-N cis-L-hydroxyproline Chemical compound O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 claims description 3
- 230000003000 nontoxic Effects 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- LELJBJGDDGUFRP-UHFFFAOYSA-N serine hydroxamate Chemical compound OCC(N)C(=O)NO LELJBJGDDGUFRP-UHFFFAOYSA-N 0.000 claims description 3
- 229960003732 tyramine Drugs 0.000 claims description 3
- VHVGNTVUSQUXPS-GVHYBUMESA-N (2R)-2-amino-3-hydroxy-3-phenylpropanoic acid Chemical group OC(=O)[C@H](N)C(O)C1=CC=CC=C1 VHVGNTVUSQUXPS-GVHYBUMESA-N 0.000 claims description 2
- BLZXFNUZFTZCFD-IBGZPJMESA-N (2S)-2,6-bis(phenylmethoxycarbonylamino)hexanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)CCCNC(=O)OCC1=CC=CC=C1 BLZXFNUZFTZCFD-IBGZPJMESA-N 0.000 claims description 2
- WFQVSLVQIFFQQN-LURJTMIESA-N (2S)-2-formamido-3-(1H-imidazol-3-ium-5-yl)propanoate Chemical compound O=CN[C@H](C(=O)O)CC1=CN=CN1 WFQVSLVQIFFQQN-LURJTMIESA-N 0.000 claims description 2
- VJROPLWGFCORRM-YFKPBYRVSA-N (2S)-2-methylbutan-1-amine Chemical compound CC[C@H](C)CN VJROPLWGFCORRM-YFKPBYRVSA-N 0.000 claims description 2
- FYCWLJLGIAUCCL-DMTCNVIQSA-N (2S,3R)-2-azaniumyl-3-methoxybutanoate Chemical compound CO[C@H](C)[C@H](N)C(O)=O FYCWLJLGIAUCCL-DMTCNVIQSA-N 0.000 claims description 2
- XDEFUBWPXAOAME-OWOJBTEDSA-N (E)-2,6-diaminohex-4-enoic acid Chemical compound NC\C=C\CC(N)C(O)=O XDEFUBWPXAOAME-OWOJBTEDSA-N 0.000 claims description 2
- GRGCKTAOXPUFNW-UHFFFAOYSA-N 1-(2,6-dichlorophenyl)-N-(2-phenylethyl)methanimine Chemical compound ClC1=CC=CC(Cl)=C1C=NCCC1=CC=CC=C1 GRGCKTAOXPUFNW-UHFFFAOYSA-N 0.000 claims description 2
- FBGSFQJJKHSURA-UHFFFAOYSA-N 1-methylpyrrolidin-2-amine Chemical compound CN1CCCC1N FBGSFQJJKHSURA-UHFFFAOYSA-N 0.000 claims description 2
- XNIOWJUQPMKCIJ-UHFFFAOYSA-N 2-(benzylamino)ethanol Chemical compound OCCNCC1=CC=CC=C1 XNIOWJUQPMKCIJ-UHFFFAOYSA-N 0.000 claims description 2
- PTLIJFYEFDUQGQ-UHFFFAOYSA-N 2-(difluoroamino)-2,3,4,4-tetrafluoro-3-methylbutanoic acid Chemical compound FC(F)C(F)(C)C(F)(N(F)F)C(O)=O PTLIJFYEFDUQGQ-UHFFFAOYSA-N 0.000 claims description 2
- WHOLKBDVEGPXOL-UHFFFAOYSA-N 2-[(2,6-dichlorophenyl)methylamino]ethanol Chemical compound OCCNCC1=C(Cl)C=CC=C1Cl WHOLKBDVEGPXOL-UHFFFAOYSA-N 0.000 claims description 2
- YWVHQKZLHBDZLG-UHFFFAOYSA-N 2-amino-3-(1H-imidazol-5-yl)-2-methylpropanoic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)C(N)(C)CC1=CN=CN1 YWVHQKZLHBDZLG-UHFFFAOYSA-N 0.000 claims description 2
- GJXKLTCCHFCTDC-UHFFFAOYSA-N 2-amino-3-(3-aminocyclohexyl)propanoic acid Chemical compound OC(=O)C(N)CC1CCCC(N)C1 GJXKLTCCHFCTDC-UHFFFAOYSA-N 0.000 claims description 2
- DGJTWBMINQYSMS-UHFFFAOYSA-N 2-amino-4,4-dichlorobutanoic acid Chemical compound OC(=O)C(N)CC(Cl)Cl DGJTWBMINQYSMS-UHFFFAOYSA-N 0.000 claims description 2
- ZJAGBNLNDKYYNL-UHFFFAOYSA-N 2-amino-4-methylhex-4-enoic acid Chemical compound CC=C(C)CC(N)C(O)=O ZJAGBNLNDKYYNL-UHFFFAOYSA-N 0.000 claims description 2
- VWHRYODZTDMVSS-UHFFFAOYSA-N 2-azaniumyl-3-(3-fluorophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC=CC(F)=C1 VWHRYODZTDMVSS-UHFFFAOYSA-N 0.000 claims description 2
- WTOFYLAWDLQMBZ-UHFFFAOYSA-N 2-azaniumyl-3-thiophen-2-ylpropanoate Chemical compound OC(=O)C(N)CC1=CC=CS1 WTOFYLAWDLQMBZ-UHFFFAOYSA-N 0.000 claims description 2
- LQTSGYSPPYNZCS-UHFFFAOYSA-N 3-(1H-imidazol-5-yl)propane-1,2-diamine Chemical compound NCC(N)CC1=CNC=N1 LQTSGYSPPYNZCS-UHFFFAOYSA-N 0.000 claims description 2
- UNOVJYROJDZHIO-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)propane-1,2-diamine Chemical compound NCC(N)CC1=C(Cl)C=CC=C1Cl UNOVJYROJDZHIO-UHFFFAOYSA-N 0.000 claims description 2
- BXRLWGXPSRYJDZ-VKHMYHEASA-N 3-cyano-L-alanine zwitterion Chemical compound OC(=O)[C@@H](N)CC#N BXRLWGXPSRYJDZ-VKHMYHEASA-N 0.000 claims description 2
- VIIAUOZUUGXERI-UHFFFAOYSA-N 3-fluorotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(O)C(F)=C1 VIIAUOZUUGXERI-UHFFFAOYSA-N 0.000 claims description 2
- CXFFQOZYXJHZNJ-UHFFFAOYSA-N 3-phenylpropane-1,2-diamine Chemical compound NCC(N)CC1=CC=CC=C1 CXFFQOZYXJHZNJ-UHFFFAOYSA-N 0.000 claims description 2
- JAYBQRKXEFDRER-UHFFFAOYSA-N 4-(2-amino-1-hydroxypropyl)phenol Chemical compound CC(N)C(O)C1=CC=C(O)C=C1 JAYBQRKXEFDRER-UHFFFAOYSA-N 0.000 claims description 2
- SODXFOVXZATGPJ-UHFFFAOYSA-N 4-amino-4-phosphonobutanoic acid Chemical compound OP(=O)(O)C(N)CCC(O)=O SODXFOVXZATGPJ-UHFFFAOYSA-N 0.000 claims description 2
- WCVPFJVXEXJFLB-UHFFFAOYSA-N 4-aminobutanamide Chemical compound NCCCC(N)=O WCVPFJVXEXJFLB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
- XWHHYOYVRVGJJY-UHFFFAOYSA-N 4-fluorophenylalanine Chemical compound OC(=O)C(N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-UHFFFAOYSA-N 0.000 claims description 2
- XFGVJLGVINCWDP-UHFFFAOYSA-N 5,5,5-trifluoroleucine Chemical compound FC(F)(F)C(C)CC(N)C(O)=O XFGVJLGVINCWDP-UHFFFAOYSA-N 0.000 claims description 2
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan zwitterion Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 claims description 2
- 229940030486 ANDROGENS Drugs 0.000 claims description 2
- 229960005261 Aspartic Acid Drugs 0.000 claims description 2
- 239000004470 DL Methionine Substances 0.000 claims description 2
- AEOCXXJPGCBFJA-UHFFFAOYSA-N Ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 2
- GGLZPLKKBSSKCX-UHFFFAOYSA-N Ethionine Chemical compound CCSCCC(N)C(O)=O GGLZPLKKBSSKCX-UHFFFAOYSA-N 0.000 claims description 2
- 206010020112 Hirsutism Diseases 0.000 claims description 2
- STVVMTBJNDTZBF-VIFPVBQESA-N L-Phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 claims description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
- GSYTVXOARWSQSV-BYPYZUCNSA-N L-methioninamide Chemical compound CSCC[C@H](N)C(N)=O GSYTVXOARWSQSV-BYPYZUCNSA-N 0.000 claims description 2
- OQGRFQCUGLKSAV-JTQLQIEISA-N N-[(3S)-2,6-dioxopiperidin-3-yl]-2-phenylacetamide Chemical compound N([C@@H]1C(NC(=O)CC1)=O)C(=O)CC1=CC=CC=C1 OQGRFQCUGLKSAV-JTQLQIEISA-N 0.000 claims description 2
- FBTSQILOGYXGMD-LURJTMIESA-N Nitrotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C([N+]([O-])=O)=C1 FBTSQILOGYXGMD-LURJTMIESA-N 0.000 claims description 2
- 229960002888 Oxitriptan Drugs 0.000 claims description 2
- WWPITPSIWMXDPE-UHFFFAOYSA-N Para-Chloroamphetamine Chemical compound CC(N)CC1=CC=C(Cl)C=C1 WWPITPSIWMXDPE-UHFFFAOYSA-N 0.000 claims description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N dopa Chemical compound OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N ethanolamine Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 2
- 229960002001 ethionamide Drugs 0.000 claims description 2
- 150000004702 methyl esters Chemical class 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
- LCNVWDVWJBEJTA-UHFFFAOYSA-N (2-nitro-1-phenylpropyl) acetate Chemical compound [O-][N+](=O)C(C)C(OC(C)=O)C1=CC=CC=C1 LCNVWDVWJBEJTA-UHFFFAOYSA-N 0.000 claims 1
- ZIWHMENIDGOELV-BKLSDQPFSA-N (2S)-4-fluoropyrrolidine-2-carboxylic acid Chemical group OC(=O)[C@@H]1CC(F)CN1 ZIWHMENIDGOELV-BKLSDQPFSA-N 0.000 claims 1
- CZCIKBSVHDNIDH-UHFFFAOYSA-N 3-(1H-indol-3-yl)-2-(methylazaniumyl)propanoate Chemical compound C1=CC=C2C(CC(NC)C(O)=O)=CNC2=C1 CZCIKBSVHDNIDH-UHFFFAOYSA-N 0.000 claims 1
- UQTZMGFTRHFAAM-ZETCQYMHSA-N 3-Iodotyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C(I)=C1 UQTZMGFTRHFAAM-ZETCQYMHSA-N 0.000 claims 1
- DBLDQZASZZMNSL-QMMMGPOBSA-N 4-[(2S)-2-amino-3-hydroxypropyl]phenol Chemical compound OC[C@@H](N)CC1=CC=C(O)C=C1 DBLDQZASZZMNSL-QMMMGPOBSA-N 0.000 claims 1
- 239000004475 Arginine Substances 0.000 claims 1
- 229960001230 Asparagine Drugs 0.000 claims 1
- QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 claims 1
- 229960002989 Glutamic Acid Drugs 0.000 claims 1
- 239000004471 Glycine Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 229960000310 ISOLEUCINE Drugs 0.000 claims 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 1
- 239000004472 Lysine Substances 0.000 claims 1
- AJYJGTVCJWGEMR-UHFFFAOYSA-N N-[(2,6-dichlorophenyl)methyl]-2-phenylethanamine Chemical compound ClC1=CC=CC(Cl)=C1CNCCC1=CC=CC=C1 AJYJGTVCJWGEMR-UHFFFAOYSA-N 0.000 claims 1
- SCIFESDRCALIIM-UHFFFAOYSA-N N-methylphenylalanine Chemical compound CNC(C(O)=O)CC1=CC=CC=C1 SCIFESDRCALIIM-UHFFFAOYSA-N 0.000 claims 1
- 229960005190 Phenylalanine Drugs 0.000 claims 1
- 239000004473 Threonine Substances 0.000 claims 1
- 235000004279 alanine Nutrition 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 claims 1
- 235000009582 asparagine Nutrition 0.000 claims 1
- 235000003704 aspartic acid Nutrition 0.000 claims 1
- 235000018417 cysteine Nutrition 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 235000013922 glutamic acid Nutrition 0.000 claims 1
- 239000004220 glutamic acid Substances 0.000 claims 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- FQQRYHVRMAVZHZ-UHFFFAOYSA-N oxalic acid;(4-propan-2-yloxypyrrolidin-2-yl)methanamine Chemical compound OC(=O)C(O)=O.CC(C)OC1CNC(CN)C1 FQQRYHVRMAVZHZ-UHFFFAOYSA-N 0.000 claims 1
- 239000004474 valine Substances 0.000 claims 1
- ZBYVTTSIVDYQSO-REOHCLBHSA-N β-L-aspartylhydroxamic acid Chemical compound [O-]C(=O)[C@@H]([NH3+])CC(=O)NO ZBYVTTSIVDYQSO-REOHCLBHSA-N 0.000 claims 1
- 210000004209 Hair Anatomy 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- WVDDGKGOMKODPV-UHFFFAOYSA-N benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- SZXQTJUDPRGNJN-UHFFFAOYSA-N Dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 5
- 210000000056 organs Anatomy 0.000 description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L MgCl2 Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 241000699800 Cricetinae Species 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 210000003780 Hair Follicle Anatomy 0.000 description 3
- 229960004319 Trichloroacetic Acid Drugs 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N Trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000004018 waxing Methods 0.000 description 3
- PWDYHRMBGRYCAP-UHFFFAOYSA-N 2-amino-3-methylsulfanylbutanoic acid Chemical compound CSC(C)C(N)C(O)=O PWDYHRMBGRYCAP-UHFFFAOYSA-N 0.000 description 2
- 229940030495 ANTIANDROGEN SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM Drugs 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Natural products CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- RUOJZAUFBMNUDX-UHFFFAOYSA-N Propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 2
- 230000002280 anti-androgenic Effects 0.000 description 2
- 239000000051 antiandrogen Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 238000005868 electrolysis reaction Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- WVHMOENDFIKQBZ-QMMMGPOBSA-N (2S)-3-phenyl-2-[(2,2,2-trifluoroacetyl)amino]propanoic acid Chemical compound FC(F)(F)C(=O)N[C@H](C(=O)O)CC1=CC=CC=C1 WVHMOENDFIKQBZ-QMMMGPOBSA-N 0.000 description 1
- ZIWHMENIDGOELV-IMJSIDKUSA-N (2S,4S)-4-fluoropyrrolidin-1-ium-2-carboxylate Chemical compound OC(=O)[C@@H]1C[C@H](F)CN1 ZIWHMENIDGOELV-IMJSIDKUSA-N 0.000 description 1
- AYBALPYBYZFKDS-UHFFFAOYSA-N (3-acetyloxy-2-nitro-3-phenylpropyl) acetate Chemical compound CC(=O)OCC([N+]([O-])=O)C(OC(C)=O)C1=CC=CC=C1 AYBALPYBYZFKDS-UHFFFAOYSA-N 0.000 description 1
- PCDQPRRSZKQHHS-XVFCMESISA-N ({[({[(2R,3S,4R,5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-XVFCMESISA-N 0.000 description 1
- CZSQAYAIWDEOSA-UHFFFAOYSA-N 2-amino-3-(1H-indol-3-yl)butanoic acid Chemical compound C1=CC=C2C(C(C(N)C(O)=O)C)=CNC2=C1 CZSQAYAIWDEOSA-UHFFFAOYSA-N 0.000 description 1
- BOWUOGIPSRVRSJ-UHFFFAOYSA-N 2-aminohexano-6-lactam Chemical compound NC1CCCCNC1=O BOWUOGIPSRVRSJ-UHFFFAOYSA-N 0.000 description 1
- ZYVMPHJZWXIFDQ-UHFFFAOYSA-N 2-azaniumyl-2-methyl-4-methylsulfanylbutanoate Chemical compound CSCCC(C)(N)C(O)=O ZYVMPHJZWXIFDQ-UHFFFAOYSA-N 0.000 description 1
- NYCRCTMDYITATC-UHFFFAOYSA-N 2-azaniumyl-3-(2-fluorophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC=CC=C1F NYCRCTMDYITATC-UHFFFAOYSA-N 0.000 description 1
- IRZQDMYEJPNDEN-UHFFFAOYSA-N 2-azaniumyl-3-phenylbutanoate Chemical compound OC(=O)C(N)C(C)C1=CC=CC=C1 IRZQDMYEJPNDEN-UHFFFAOYSA-N 0.000 description 1
- SGRCVQDBWHCTIS-UHFFFAOYSA-N 2-nonanoyloxypropyl nonanoate Chemical compound CCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCC SGRCVQDBWHCTIS-UHFFFAOYSA-N 0.000 description 1
- PNGCRFWYSRUQTB-QRPNPIFTSA-N 4-[(2S)-2-amino-3-hydroxypropyl]phenol;hydrochloride Chemical compound Cl.OC[C@@H](N)CC1=CC=C(O)C=C1 PNGCRFWYSRUQTB-QRPNPIFTSA-N 0.000 description 1
- 101700024603 ANNU Proteins 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 1
- 102000005758 Adenosylmethionine Decarboxylase Human genes 0.000 description 1
- 108010070753 Adenosylmethionine Decarboxylase Proteins 0.000 description 1
- 210000003467 Cheek Anatomy 0.000 description 1
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N DL-serine Chemical compound OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102000006640 EC 2.3.2.2 Human genes 0.000 description 1
- 101700066372 ECM38 Proteins 0.000 description 1
- 101700082072 GGT1 Proteins 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
- 210000000088 Lip Anatomy 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N Norvaline Chemical compound CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- 102000028557 Ornithine Decarboxylase Human genes 0.000 description 1
- 108091022025 Ornithine Decarboxylase Proteins 0.000 description 1
- 210000004761 Scalp Anatomy 0.000 description 1
- 101700034322 TGAS Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Tris Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 101710038776 acyI Proteins 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 230000001413 cellular Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N edta Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 230000003659 hair regrowth Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-L oxalate Chemical compound [O-]C(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-L 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 231100000486 side effect Toxicity 0.000 description 1
- 101700012968 tgl Proteins 0.000 description 1
- 230000001225 therapeutic Effects 0.000 description 1
- 230000000699 topical Effects 0.000 description 1
- HYOWVAAEQCNGLE-UHFFFAOYSA-N α-Methylphenylalanine Chemical compound OC(=O)C(N)(C)CC1=CC=CC=C1 HYOWVAAEQCNGLE-UHFFFAOYSA-N 0.000 description 1
Abstract
Mammalian hair growth is reduced by applying an inhibitor of aminoacyl-tRNA synthetase to the skin.
Description
REDUCTION OF HAIR GROWTH
The invention relates to the reduction of hair growth in mammals. A major function of hair in mammals is to provide protection against the environment. However, this function has been lost in humans in essentially, in which the hair is preserved or removed from various parts of the body essentially for aesthetic reasons. For example, it is generally preferred to have hair on the scalp but not on the face. Several procedures have been used to remove unwanted hair, including shaving, electrolysis, waxing creams or lotions, waxing, tearing, and therapeutic antiandrogens. These conventional methods generally have disadvantages associated therewith. Shaving, for example, can cause scratches and cuts, and may leave a perception of an increase in growth in the proportion of hair regrowth. Shaving can also leave an undesirable wall. Electrolysis, on the other hand, can in a treated area keep it free of hair for "" long periods of time, but it can be expensive, painful, and sometimes scarring. Hair removal creams,
REF .: 33176 Although very effective, they are typically not recommended for frequent use due to their high potential irritation. The waxing and tearing can cause pain, discomfort, and poor hair removal. Finally, antiandrogens - which have to be used to treat female hirsutism - can have unwanted side effects.
It has previously been revealed that the proportion and type of hair growth can be changed by the application of the inhibitor of certain enzymes on the skin. These inhibitors include the inhibitors of 5-alpha reductase, ornithine decarboxylase, s-adenosylmethionine decarboxylase, gamma-glutamyl transpeptidase, and transglutaminase. See, for example, Breuer et al., U.S. Pat. No. 4,885,289; Shander, U.S. Pat. No. 4,720,489; Ahluwalia, U.S. Pat. 5,095,007; Ahluwalia et al., U.S. Pat. No. 5,096,911; Shander et al.], U.S. Pat No. 5,132,293; and Shander et al, U.S. Pat. No. 5,143,925.
Aminoacyl-tRNA synthetases are a family of enzymes that are involved in the synthesis of cellular protein. In particular, the enzymes involved in the activation of amino acids and the subsequent binding of amino acids to the corresponding tRNA. There is at least one inoperable-tRNA for each of the twenty natural amino acids that protein molecules make. Aminoacyl-tRNA synthetase are described, for example, in P, Schi mel (1987) Ann. Rev. Biochem. 65: 125-158.
It has now been found that unwanted hair growth in mammals (including man) - hair growth particularly stimulated by androgen - can be reduced by the application of a dermatologically acceptable skin composition including an aminoacyl-tRNA inhibitor. synthetase in an effective amount to reduce hair growth. The growth of unwanted hair which is reduced may be normal hair growth, or hair growth as a result of an abnormality or a condition of a disease.
Examples of aminoacyl-tRNA inhibitors include S-trityl-L-cysteine: L-asparaginamide; 4-aza-DL-leucine; DL-serine hydroxamate; proflavine (hemisulfate salt); L-isoleucinol; N-phenylglycine; L-leucinol; L-methioninol; fe-leu-amide; tyramine; L-isoleucinol; 3, 4-dehydro-DL-proline;
S-carbamyl-L-cysteine; α-methyl-DL-methionine; chlorine-L-alanine;
cis-hydroxy proline; L-prolinol; L-histidonol; L-tirprofan hydroxamate; DL-4-thiaisoleucine; DL-amino-e-caprolactam; L-aspartic acid amide; DL-β-hydroxynorvaline; cis-4-fluoro-L-proline; trans-4-fluoro-L-carboxylic acid; α-methyl-DL-histidine; N-formyl-L-histidine; L-2-amino-3-sulfamoylpropinoic acid; ß-hydroxamate of L-aspartic acid; β-cyano-L-alanine; selenocistamine; 4-amino-n-butyric acid amide; DL-5-hydroxylysine; L-lisinhydroxamate; 3- (N-phenylacetyl) amino-2,6-piperidinedione (antineoplaston A10); 4-amino-4-phosphonobutyric acid; ethionamide; 1,2-diamino-3 (4-imidazolyl) propane (histidinamine); ct-methylhistidine; (S) -2-methylbutylamine; L-O-methyl threonine; DL-armentomycin (2-amino-4,4-dichlorobutyric acid); DL-3-dehydroarmentomycin; DL-3-dihydroxyleucine; 5, 5, 5-trifluoro-DL-leucine; β- (3-aminocyclohexyl) -DL-alanine; DL-p-chloroamphetamine; trans-2,6-diaminohex-4-enoic acid; DL-2, 6-diftali idocaproic acid methyl ester; DL-5-hydroxylysine; L-lisinhydroxamate; DL-4-oxalisin; DL-4-selenalysin; L-methioninamide; 2-amino-4-methylhex-4-enoic acid; (SS, 2S) -2-amino-1-phenyl-1,3-propanediol; N-benzyl-D-amphetamine; N-benzyl-L-phenylamine; N-benzyl-D-phenylethylamine; 1,3-bis (acetoxy) -2-nitro-l-phenylpropane (phenytopane); 1,2-diamino-3- (2,6-dichloro-phenyl) propane; 1,2-diamino-3-hydroxy-5-phenylpentane; 1,2-diamino-3-phenylpropane; N- (2,6-dichlorobenzylidene) -2-phenylethylamine; N- (2,6-dichlorobenzyl) 2-phenylostylamine; N- (4-fluorobenzyl) -L-phenylalanine; DL-2-fluorophenylalanine; 2-hydroxyethyl-2-phenylammonium sulfate; α- and β-methyl-DL-phenylalanine; L-phenylalaninol; L-a-phenylglycerin; DL-threo-β-phenylserine; β-2-thienyl-DL-alanine; cyclohexyl ester of N-trifluoroacetyl-L-phenylalanine; oxalate 2-amj inomethyl-4-isopropyloxypyrrolidine; 2-amino-methylpyrrolidine; L-4-thiaproline; N-benzylethanolamine; N- (2,6-dichlorobenzyl) ethanolamine; N- (2,6-dichloro-benzylidone) ethanolamine; DL-ßP-hydroxyleucine; 1,2-diamino-5-phenyl-3-pentanol; DL-7-azatriptofan; DL-4- and DL-6-fluorotriptofan; 5-hydroxy-tryptamine; L-5-hydroxytryptophan; DL-a-methyltriptamine; α- and β-methyl-DL-tryptophan; Tryptamine; DL-2-amino-1- (4-hydroxyphenyl) -1-propanol; DL-3-fluoro-tyrosine; 3-iodine-L-tyrosine; 3-nitro-L-tyrosine; L-tyrosinol-HCl; L-threo-2-amino-3-chlorobutyric acid; hexafluoro-DL-valine; DL-norvaline; L-4-tialisine; DL-ethionine; N, N'-di-CBZ-L-lysine; DL-3-fluorophenylalanine; DL-4-fluorophenyl-alanine; and DL-3,4-dihydroxyphenylalanine. These compounds are known-s-.
Many of the examples of aminoacyl-tRNA inhibitors are amino acids and inhibit the aminoacyl-tRNA synthetase associated with the amino acid analogs, although a particular inhibitor can sometimes inhibit the aminoacyl-tRNA synthetase associated with more than one amino acid. The term "The inhibitor of [amino acid name] aminoacyl-RNAt synthetase" is used herein, a compound that inhibits at least the aminoacyl-tRNA associated with the amino acid. The amino acid can be one of the 20 naturally occurring amino acids (e.g. leucine, serine etc), or some other amino acid. As used herein, "Aminoacyl-RNAT synthetase inhibitors" and an "Aminoacyl-tRNA synthetase inhibitor" means a compound that inhibits one or more aminoacyl-tRNA synthetase.
The aminoacyl-tRNA synthetase inhibitor is preferably incorporated into a topical composition that includes a non-toxic dermatologically acceptable carrier or carrier or a carrier which is adapted to be expanded on the skin. Examples of suitable carriers are acetones, alcohols, or a cream, lotion, or gel which can effectively deliver the active compound. A vehicle is disclosed in U.S. Pat. No. 5,648,394. In sum, a better penetration can be added to the vehicle to encourage the increase in the effectiveness of the formulation.
The concentration of the inhibitor in the composition can vary over a wide range to the saturated solution, preferably from 0.1% to 30% by weight or even more; The reduction in hair growth increases with the increase in the amount of inhibitor applied per unit area of skin. The maximum amount applied effectively is limited only by the proportion of the inhibitor which penetrates the skin. The effective amounts may vary, for example, from 10 to 3000 micrograms or more per square centimeter of skin.
A composition may include more than one aminoacyl-tRNA synthetase inhibitor. For example, the composition may include two inhibitors of an aminoacyl-tRNA synthetase associated with a particular amino acid, or may include an inhibitor of an aminoacyl-tRNA synthetase associated with a first amino acid and an inhibitor of an associated aminoacyl-RNAt synthetase with a second amino acid. The composition may optionally also include another compound that are known to reduce hair growth where they are typically applied.
The composition should be topically applied in a selected area of the body in which it is desired to reduce hair growth. For example; the composition can be applied to the face, particularly in the area of the face beard, i.e., the cheek, the neck, the upper lip, and the chin. The composition can also be applied on the legs, arms, torso and armpits. The composition is particularly suitable for reducing unwanted hair growth in women victims of irsutism or in other conditions. The duration of treatment may vary depending on how the reduction of hair growth is perceived, for example, the separation and location of unwanted hair. In humans, the composition, for example, can be applied once or twice a day, or even more frequently, from two weeks to six months (e.g. three months) to achieve the realization of the reduction of hair growth. The reduction in hair growth is demonstrated when the frequency or removal of the hair is reduced, or the subject perceives less hair at the treated site, or quantitatively, when the hair weight removed by shaving (ie, the hair mass) It is reduced. ~ Golden Syrian intact male hamsters are considered acceptable models for the growth of human hair on lateral sides that have oval shaped bodies, one on each side, each in a diameter greater than approximately 8 mm, whose thickness Black grows and coarse hair is similar to the hair of the human beard. These organs produce hair in response to androgens in the hamster. To evaluate the effectiveness of a composition that includes an aminoacyl-tRNA synthetase inhibitor, the ijar organs of each of a Hamster group are shaved. For an organ of each animal 10 μl of vehicle was applied only once a day, while the other organ of each animal was applied an equal amount of vehicle containing an aminoacyl-tRNA inhibitor. After thirteen applications (one application per day for five days a week), the ijar organs are shaved and the amount of hair recovered (the hair mass) of each is heavy. The percentage of hair growth reduction is calculated by subtracting the value of the hair mass (mg) from the treated side of the test compound from the value of the hair mass of the treated side of the vehicle; and the delta value obtained is then divided by the value of the hair mass of the treated side of the vehicle, and the resulting number is multiplied by 100.
The test described above is attributed here as the essay "The Golden Syrian Hamster". Preferred compositions provide a reduction in hair growth of a little less than 25%, more often a little less than 50% and still more frequently a little less than 60% when examined in the Golden Syrian Hamster test. A number of compositions containing an inhibitor of aminoacyl-tRNA synthetase synthesis was examined in the Golden Syrian Hamster assay; The results are shown in Table 1 :
TABLE 1 Inhibitor Dose Vehicle £ H Control Treaty% of () (mg) (mg) inhibition
S-trityl-L-cysteine 7.5 A 6.5 0.35 +/- .10 1.64 +/- .14 80 +/- .6
L-asparaginamide 10 B 5 1.00 +/-, .24 2.60 +/- .42 66 +/- 7
4-aza-DL-leucine ° 2HCl 10 B 5.5 0.70 +/- .08 2.02 +/- .27 66 +/- 3
DL-a-amino-e-caprolactam 10 D 6.6 0.90 +/-, .16 2.30 +/- .11 59 +/- 9
hydroxamate DL-serine 10 B 7.5 1.28 +/- .17 2.94 +/- .34 56 +/- 5
Hemisulphate proflavine 10 C 5.5 1.41 +/- .19 3.04 +/- .24 52 +/- 7
L-Isoleucinol 10 B 7.5 1.20 +/- .21 2.40 +/- .38 51 +/- 9
N-phenylglycine 10 D 3.0 1.37 +/- .19 2.84 +/- .22 51 +/- 8
L-leucinol 10 E 8.0 1.55 +/- .22 2.86 +/- .34 46 +/- 4
L-prolinol 10 B 7.5 1.31 +/- .19 2.43 +/- .26 45 +/- 6
L-histidonal 10 D 7.4 1.88 +/- .26 3.46 +/- .18 45 +/- 7
L-methioninol 10 E 7.5 1.55 +/- .14 2.72 +/- .27 42 +/- 3
Fe-leu-amide 10 F 4.5 1.18 +/- .23 1.95 +/- .19 41 +/- 8
Tyramine 10 B 5.0 1.20 +/- .19 2.10 +/- .13 41 +/- 10
3, 4-dehydro-DL-proline 10 B 6.0 1.18 +/- .18 2.00 +/- .11 39 +/- 9
DL-β-hydroxynorvaline 10 B 6.0 0.81 +/- .15 1.40 +/- .11 38 +/- 13
S-carbamyl-L-cysteine 7.5 G 4.5 1.71 +/- .17 2.55 +/- .29 32 +/- 6
-methyl-DL-methionine 15 B 6.5 1.10 +/- .15 1.70 +/- .40 31 +/- 7 L-aspartic amide acid 10 I 6.9 1.38 +/- .14 1.99 +/- .21 30 +/- 5 Chlorine-L-alanine-HLC 10 B 4.5 2.38 +/- .27 3.26 +/- .26 25 +/- 9 Cis-hydroxy-proline 10 B 5.5 1.96 +/- .18 2.60 +/- .22 24 + / - 7 DL-4-thiaisoleucine 10 B 5.0 2.36 +/- .26 3.08 +/- .16 23 +/- 9 Lucinamide 10 B 4.6 2.13 +/- .28 2.77 +/- .26 22 +/- 10 hydroxamate L-tirprofan 10 H 8 0.88 +/- .10 1.10 +/- .15 10 +/- 17 Vehicles: A-90% H20, 6% dipropylene glycol, and 4% ethanol B-68% water, 16% ethanol, 5% propylene glycol; 5% dipropylene glycol, 4% benzyl alcohol, and 2% propylene carbonate. C-92% water, 3% propylene carboan, and 5% benzyl alcohol. D-80% ethanol, 17.5% water, 2% prolylene glycol diperlargonate (Emerest 2388), and 0.5% propylene glycol. t
E-50% dipropylene glycol and 50% ethanol. I
F-60% ethanol, 25% dimethyl sulfoxide, 13.1% water, 1.5% propylene glycol dipelargonate (Emerest 2388), and 0.38% propylene glycol. G-95.6% water and 4.4% dimethyl sulfoxide. H-100% dimethyl sulfoxide. 1-84% water, 8% ethanol, 2.5% propylene glycol, 2.5% dipropylene glycol, 2% l, benzyl alcohol, and 1% propylene carbonate.
A study of the response to dosing with S-trityl-L-cysteine indicates that an increase in the concentration of the inhibitor in the composition results in an increased reduction in hair growth. The results are shown in Table 2.
TABLE 2 Inhibition response to hair growth by the dosage of S-trityl-L-cysteine Compound Dosage pH Treated Control% inhibition (mg) S-tri-cysteine 7. 5% 6.5 0.35 +/-. 10 1. 64 +/-. 14 80 +/- 6 S-tri-il-cysteine 5% 6. 5 0. 90 +/-. 17 1. 95 +/-. 35 56 +/- 6 S-trityl-cysteine 1% 5. 5 0. 88 +/-. 10 1. 10 +/-. 15 35 +/- 9 10 Vehicle: 90% H20, 6% dipropylene glycol, 4% ethanol.
Inhibition of aminoacyl-tRNA synthetase in the hair follicle was determined using a modification of the procedure described by Hampel et al (Aminoacyl-tRNA Synthetase from Cultured CHO Cells (1979) Methods in Enzymology, Vol. LIX .PP 229-234 ). A reaction mixture containing the following was used for each assay;
50mM Tris (pH 7.4), 15mM MgCl2, 0.5mM EDTA (adjusting the pH to 7), 5mM ATP (adjusting the pH to 7, 0.35 mM
CTP, 20 μM 14C amino acid and tRNA (50μg / ml). Synthesis of leucine and serine tRNA was attempted with a buffer pH 8.6 and a concentration of 8 mM MgCl2. The reaction mixture was mixed with the hair follicle extract so that the volume of the final assay is 100μL. Typically 90-95μL of the reaction mixture are mixed with
-10μL of hair follicle extract. The reaction was carried out at 37 ° C for 60 minutes. The reaction is terminated by removing the reaction mixture and placing it on a piece of filter paper which was wet with 10% trichloroacetic acid. The filter paper was washed three times in 10% trichloroacetic acid and three times in 5% trichloroacetic acid. The filter paper was dried and the insoluble radioactivity corresponding to 14C-aminoacyl-tRNA was counted in a scintillation counter.
The incorporation of the amino acid 1C varies from 178"dpm / mM to 3.093 dpm / mM in the assays of the amino acids mentioned above.Using this assay, the incorporation of leucine into newly inhibited synthesized proteins was found.
In short, the incorporation of serine into synthesized proteins was again inhibited by DL-serine hydroxamate. Other embodiments are within the claims. DECLARATION THAT INCLUDES PROCESS It is stated that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.
Having described the invention as above, the content of the following is claimed as property.
Claims (74)
1. A method for reducing hair growth in mammals characterized in that: it is selected the area of the skin from which it is desired to reduce hair growth; and a dermatologically acceptable composition including an aminoacyl-tRNS synthetase inhibitor in an amount effective to reduce hair growth is applied in said skin area.
2. The method of claim 1, characterized in that said amino acid synthesis includes the alanine aminoacyl-tRNA synthetase.
3. The method of claim 1, characterized in that said synthesis of aminoacyl-tRNA includes that of arginine aminoacyl-tRNA synthetase.
4. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes asparagine aminoacyl-tRNA synthetase.
5. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes. aspartic acid aminoacyl-tRNA synthetase.
6. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes the cysteine aminoacyl-tRNA synthetase.
7. The method of claim 1; characterized in that said aminoacyl-tRNA synthetase includes glutamine aminoacyl-tRNA synthetase.
8. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes glutamic acid aminoacyl-tRNA synthetase.
9. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes glycine aminoacyl-tRNA synthetase.
10. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes the histidine aminoacyl-tRNA synthetase.
11. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes isoleucine aminoacyl-tRNA synthetase.
12. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes the leucine aminoacyl-tRNA synthetase.
13. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes the aminoacyl-tRNA synthetase lysine.
14. The method of claim 1, characterized in that said aminoacyl-tRNA synthetase includes methionine aminoacyl-tRNA synthetase.
15. The method of claim 1, characterized in that the aminoacyl-tRNA synthetase includes the phenylalanine aminoacyl-tRNA synthetase.
16. The method of claim 1, characterized in that the aminoacyl-tRNA synthetase includes the proline aminoacyl-tRNA synthetase.
17. The method of claim 1, characterized in that the aminoacyl-tRNA synthetase includes the serine aminoacyl-tRNA synthetase.
18. The method of claim 1, characterized in that the aminoacyl-tRNA synthetase includes the threonine aminoacyl-tRNA synthetase.
19. The method of claim 1, characterized in that the aminoacyl-tRNA synthetase includes the tryptophan aminoacyl-tRNA synthetase.
20. The method of claim 1, characterized in that the aminoacyl-tRNA synthetase includes the tyrosine aminoacyl-tRNA synthetase.
21. The method of claim 1, characterized in that the aminoacyl-tRNA synthetase includes valine aminoacyl-tRNA synthetase.
22. The method of claim 1, characterized in that said inhibitor includes S-trityl-L-cysteine.
23. The method of claim 1, characterized in that said inhibitor includes L-asparaginamide.
24. The method of claim 1, characterized in that said inhibitor includes 4-aza-DL-leucine.
25. The method of claim 1, characterized in that said inhibitor includes DL-serine hydroxamate.
26. The method of claim 1, characterized in that said inhibitor includes proflavine (hemisulfate salt).
27. The method of claim 1, characterized in that said inhibitor includes L-isoleucinol.
28. The method of claim 1, characterized in that said inhibitor includes N-phenylglycine.
29. The method of claim 1, characterized in that said inhibitor includes L-leucinol.
30. The method of claim 1, characterized in that said inhibitor includes L-methioninol.
31. The method of claim 1, characterized in inhibitor includes phe-leu-amide.
32. The method of claim 1, characterized in inhibitor includes tyramine.
33. The method of claim 1, characterized in inhibitor includes L-isoleucinol.
34. The method of claim 1, characterized in inhibitor includes 3,4-dehydro-DL-proline.
35. The method of claim 1, characterized in inhibitor includes S-carbamyl-L-cysteine.
36. The method of claim 1, characterized in inhibitor includes a-methyl-DL-methionine.
37. The method of claim 1, characterized in inhibitor includes chloro-L-alanine.
38. The method of claim 1, characterized in inhibitor includes cis-hydroxy proline.
39. The method of claim 1, characterized in inhibitor includes L-prolinol.
40. The method of claim 1, characterized in inhibitor includes t-histidonol.
41. The method of claim 1, characterized in inhibitor includes L-tirprofan hydroxamate.
42. The method of claim 1, characterized in inhibitor includes thioisoleucine.
43. The method of claim 1, characterized in inhibitor includes DL-amino-e-caprolatam.
44. The method of claim 1, characterized in inhibitor includes L-aspartic acid amide.
45. The method of claim 1, characterized in inhibitor includes DL-β-hydroxynorvaline.
46. The method of claim 1, characterized in inhibitor is selected from the group consisting of 4-fluoro-L-proline; trans-4-fluoro-L-carboxylic acid; α-methyl-DL-histidine; N-formyl-L-histidine; L-2-amino-3-sulfamoylpropionic acid; L-aspartic acid-β-hydroxamate; β-cyano-L-alanine; selenocitamin; and 4-amino-n-butyric acid amide.
47. The method of claim 1, characterized in that said inhibitor is cleaved from the group consisting of DL-5-hydroxylysine; L-lisinhydroxamate; 3- (N-phenylacetyl) amino-2,6-piperidinedione (antineoplaston A10); 4-amino-4-phosphonobutyric acid; ethionamide; 1,2-diamino-3 (4-imidazolyl) propane (histidinamine); a-methylishisidine; (S) -2-methylbutylamine; L-O-methyl threonine; and DL-armentomicin (2-amino-4, 4-dichlorobutyric acid).
48. The method of claim 1, characterized in that said inhibitor is selected from the group consisting of DL-3-dehydroarmentomycin; DL-3-hydroxyleucine; 5,5,5-trifluoro-DL-leucine; β- (3-aminocyclohexyl) -DL-alanine; DL-p-chloroamphetamine; trans-2,6-diaminohex-4-enoic acid; methyl ester of DL-2, 6-diftalimidocaproic acid; DL-5-hydroxylysine; L-lisinhydroxamate; and DL-4-oxalisin .__
49. The method of claim 1, characterized in that said inhibitor is selected from the group consisting of DL-4-selenalysin; L-methioninamide; 2-amino-4-methylhex-4-enoic acid; (SS, 2S) -2-amino-1-phenyl-1,3-propanediol; N-benzyl-D-amphetamine; N-benzyl-L-phenylalanine; N-benzyl-D-phenylethylamine; 1,3-his (acetoxy) -2-nitro-l-phenylpropane (phenytopane); and 1,2-diamino-3- (2,6-dichlorophenyl) propane.
50. The method of claim 1, characterized in that said inhibitor is selected from the group consisting of 1,2-diamino-3-hydroxy-5-phenylpentane; 1,2-diamino-3-phenylpropane; N- (2,6-dichlorobenzylidene) -2-phenylethylamine; N- (2,6-dichlorobenzyl) -2-phenylethylamine; N- (4-fluorobenzyl) -L-phenylalanine; DL-fluorophenylamine; 2-hydroxyethyl-2-phenylammonium sulfate; methyl-DL-phenylalanine; L-phenylalaninol; and L-a-phenylglycine.
51. The method of claim 1, characterized in that said inhibitor is selected from the group consisting of DL-threo-β-phenylserine; β-2-thienyl-DL-alanine; cyclohexyl ester of N-trifluoroacetyl-1-phenylalanine; oxalate 2-aminomethyl-4-isopropyloxypyrrolidine; 2-amino-methylpyrrolidine; L-4-thiaproline; N-benzylethanolamine; N- (2,6-dichlorobenzyl) ethanolamine; N- (2,6-dichlorobenzylidone) ethanolamine; and DL-β-hydroxyquinuezine.
52. The method of claim 1, characterized in that said inhibitor is selected from the group consisting of 1,2-diamino-5-phenyl-3-pentanol; DL-7-azatriptofan; DL-fluro-tryptophan; 5-hydroxytryptamine; L-5-hydroxy-tryptophan; DL-a-methyltriptamine; methyl-DL-tryptophan; Tryptamine; DL-2-amino-1- (4-hydroxyphenyl) -1-propanol; and DL-3-fluorotyrosine.
53. The method of claim 1, characterized in that said inhibitor is selected from the group consisting of 3-iodo-L-tyrosine; 3-nitro-L-tyrosine; L-tyrosinol »HCl; L-threo-2-amino-3-chlorobutyric acid; hexafluoro-DL-valine; DL-nornalin; L-4-tialisine; DL-ethionine; N, N'-di-CBZ-L-lysine; DL-3-fluorophenylalanine; DL-4-fluorophenyl-alanine; and DL-3, 4-dihydroxyphenylalanine.
54. The method of claim 1, characterized in that the concentration of said inhibitor in said composition is between 0.1% and 30%.
55. The method of claim 1, characterized in that the composition provides a reduction in hair growth of at least 20% when tested in the Golden Syrian Hamster assay.
56. The method of claim 1, characterized in that the composition provides a reduction in hair growth of at least 50% when tested in the Golden Syrian Hamster assay.
57. The method of claim 1, characterized in that the composition provides a reduction in hair growth of at least 60% when tested in the Golden Syrian Hamster test.
58. The method of claim 1, characterized in that the inhibitor is applied to the skin in an amount of about 10 to 3000 micrograms of said inhibitor per square centimeter of skin.
59. The method of claim 1, characterized in that said mammal includes the human.
60. The method of claim 59, characterized in that said skin area is on the face of the human.
61. The method of claim 59, characterized in that said skin area is on the legs of the human.
62. The method of claim 59, characterized in that said skin area is on an arm of the human.
63. The method of claim 59, characterized in that said skin area is in an armpit of the human.
64. The method of claim 59, characterized in that said area of the skin is on the torso of the human.
65. The method of claim 59, characterized in that said human is a woman victim of hirsutism.
66. The method of claim 1, characterized in that said hair growth includes hair growth stimulated by androgens.
67. A method according to any one of claims 1 to 66, characterized in that said application of said inhibitor has a cosmetic effect.
68. A method for producing a composition for inhibiting hair growth in mammals, characterized in that it comprises selecting an inhibitor of an aminoacyl-tRNA synthetase, and combining the inhibitor, in an amount effective to reduce hair growth, with a carrier or transporter Dermatologically acceptable, non-toxic.
69. A method according to claim 68, characterized in that said vehicle or conveyor is adapted to be spread on the skin of a mammal.
70. A method according to claim 68 or 69, characterized in that a cosmetic composition is produced.
71. A method according to claim 68, characterized in that said inhibitor is as defined in any of claims 2-53.
72. The new use of an aminoacyl-tRNA synthetase inhibitor to reduce hair growth.
73. A composition when used to inhibit hair growth in mammals, characterized in that it includes an inhibitor of an aminoacyl-tRNA synthetase, in an amount effective to reduce hair growth, and a dermatologically acceptable, non-toxic carrier or carrier.
74. A composition according to claim 73, characterized in that said inhibitor is as defined in any of claims 2-53. 75, A composition according to claim 73, characterized in that it is a cosmetic composition.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/935,181 | 1997-09-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA00002847A true MXPA00002847A (en) | 2001-06-26 |
Family
ID=
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5939458A (en) | Reduction of hair growth | |
US5455234A (en) | Inhibition of hair growth | |
EP0667766B1 (en) | Inhibition of hair growth | |
CA2163534C (en) | Inhibition of hair growth | |
US5468476A (en) | Reduction of hair growth | |
US5728736A (en) | Reduction of hair growth | |
CA2184170C (en) | Inhibition of hair growth | |
US5143925A (en) | Alteration of rate and character of hair growth | |
CA2316826C (en) | Reduction of hair growth | |
EP0675712A4 (en) | Reduction of hair growth employing sulfhydryl reactive compounds. | |
US5444090A (en) | Method of reducing the rate of hair growth | |
MXPA00002847A (en) | Reduction of hair growth | |
EP0563301B1 (en) | Cosmetic Process of Reducing the Rate of Mammalian Hair Growth | |
MXPA00007125A (en) | Reduction of hair growth |