GB2208149A - Pharmaceutical and cosmetic compositions based on pyridones and antibacterial agents - Google Patents
Pharmaceutical and cosmetic compositions based on pyridones and antibacterial agents Download PDFInfo
- Publication number
- GB2208149A GB2208149A GB8816916A GB8816916A GB2208149A GB 2208149 A GB2208149 A GB 2208149A GB 8816916 A GB8816916 A GB 8816916A GB 8816916 A GB8816916 A GB 8816916A GB 2208149 A GB2208149 A GB 2208149A
- Authority
- GB
- United Kingdom
- Prior art keywords
- composition according
- carbon atoms
- erythromycin
- ppm
- composition
- 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
- 239000000203 mixture Substances 0.000 title claims description 56
- 239000003242 anti bacterial agent Substances 0.000 title claims description 17
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 title claims description 7
- 239000002537 cosmetic Substances 0.000 title claims description 6
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 33
- 206010000496 acne Diseases 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 229960003276 erythromycin Drugs 0.000 claims description 21
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 18
- 150000002148 esters Chemical class 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical class CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims description 14
- -1 methoxymethyl halogen Chemical class 0.000 claims description 14
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 claims description 13
- 229960002227 clindamycin Drugs 0.000 claims description 13
- 229960005287 lincomycin Drugs 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 6
- JYGXADMDTFJGBT-VWUMJDOOSA-N Hydrocortisone Natural products O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- OIQJEQLSYJSNDS-UHFFFAOYSA-N piroctone Chemical compound CC(C)(C)CC(C)CC1=CC(C)=CC(=O)N1O OIQJEQLSYJSNDS-UHFFFAOYSA-N 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003963 antioxidant agent Substances 0.000 claims description 4
- 125000003118 aryl group Chemical group 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
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 239000003410 keratolytic agent Substances 0.000 claims description 4
- 239000006210 lotion Substances 0.000 claims description 4
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 claims description 4
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 3
- OYHQOLUKZRVURQ-HZJYTTRNSA-M 9-cis,12-cis-Octadecadienoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC([O-])=O OYHQOLUKZRVURQ-HZJYTTRNSA-M 0.000 claims description 3
- 229960000890 hydrocortisone Drugs 0.000 claims description 3
- 229940049918 linoleate Drugs 0.000 claims description 3
- 239000003120 macrolide antibiotic agent Substances 0.000 claims description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 3
- 229960004889 salicylic acid Drugs 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- PNCWHIAZZSDHPU-UHFFFAOYSA-N 2-benzylsulfanylethanamine Chemical compound NCCSCC1=CC=CC=C1 PNCWHIAZZSDHPU-UHFFFAOYSA-N 0.000 claims description 2
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical group C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 2
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 2
- 229960002537 betamethasone Drugs 0.000 claims description 2
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 claims description 2
- 229940036350 bisabolol Drugs 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 229960003720 enoxolone Drugs 0.000 claims description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- RYVMUASDIZQXAA-UHFFFAOYSA-N pyranoside Natural products O1C2(OCC(C)C(OC3C(C(O)C(O)C(CO)O3)O)C2)C(C)C(C2(CCC3C4(C)CC5O)C)C1CC2C3CC=C4CC5OC(C(C1O)O)OC(CO)C1OC(C1OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OCC(O)C(O)C1O RYVMUASDIZQXAA-UHFFFAOYSA-N 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 239000002294 steroidal antiinflammatory agent Substances 0.000 claims description 2
- 230000003637 steroidlike Effects 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 239000002562 thickening agent Substances 0.000 claims description 2
- SLYPOVJCSQHITR-UHFFFAOYSA-N tioxolone Chemical compound OC1=CC=C2SC(=O)OC2=C1 SLYPOVJCSQHITR-UHFFFAOYSA-N 0.000 claims description 2
- 229960003070 tioxolone Drugs 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims 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 claims 2
- DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 claims 1
- 239000004150 EU approved colour Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 1
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 claims 1
- 125000000017 cortisol group Chemical group 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 229960002593 desoximetasone Drugs 0.000 claims 1
- VWVSBHGCDBMOOT-IIEHVVJPSA-N desoximetasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@@H]2O VWVSBHGCDBMOOT-IIEHVVJPSA-N 0.000 claims 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims 1
- XAMAATKKOCZRPP-UHFFFAOYSA-N dodecyl hydrogen sulfate;propanoic acid Chemical compound CCC(O)=O.CCCCCCCCCCCCOS(O)(=O)=O XAMAATKKOCZRPP-UHFFFAOYSA-N 0.000 claims 1
- 229950000206 estolate Drugs 0.000 claims 1
- 229960001347 fluocinolone acetonide Drugs 0.000 claims 1
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 claims 1
- POUMFISTNHIPTI-BOMBIWCESA-N hydron;(2s,4r)-n-[(1r,2r)-2-hydroxy-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide;chloride Chemical group Cl.CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 POUMFISTNHIPTI-BOMBIWCESA-N 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- 229960000905 indomethacin Drugs 0.000 claims 1
- 229940099584 lactobionate Drugs 0.000 claims 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 claims 1
- 229960001595 lincomycin hydrochloride Drugs 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 claims 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 claims 1
- 239000002304 perfume Substances 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 229930006677 Erythromycin A Natural products 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 230000002757 inflammatory effect Effects 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- 101150041968 CDC13 gene Proteins 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 238000004452 microanalysis Methods 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241000555688 Malassezia furfur Species 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000032050 esterification Effects 0.000 description 4
- 238000005886 esterification reaction Methods 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 229950001046 piroctone Drugs 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 230000003255 anti-acne Effects 0.000 description 3
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 229960005280 isotretinoin Drugs 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 229930002330 retinoic acid Natural products 0.000 description 3
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- TYQXKHPOXXXCTP-CSLYCKPJSA-N erythromycin A 2'-propanoate Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)OC(=O)CC)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 TYQXKHPOXXXCTP-CSLYCKPJSA-N 0.000 description 2
- 229950001028 erythromycin propionate Drugs 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 150000002169 ethanolamines Chemical class 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 150000004508 retinoic acid derivatives Chemical class 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- NNRXCKZMQLFUPL-WBMZRJHASA-N (3r,4s,5s,6r,7r,9r,11r,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione;(2r,3 Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O.O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 NNRXCKZMQLFUPL-WBMZRJHASA-N 0.000 description 1
- ZXBDZLHAHGPXIG-VTXLJDRKSA-N (3r,4s,5s,6r,7r,9r,11r,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione;(2r,3 Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O.O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ZXBDZLHAHGPXIG-VTXLJDRKSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical class CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- ARXJGSRGQADJSQ-UHFFFAOYSA-N 1-methoxypropan-2-ol Chemical compound COCC(C)O ARXJGSRGQADJSQ-UHFFFAOYSA-N 0.000 description 1
- JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
- QCAHUFWKIQLBNB-UHFFFAOYSA-N 3-(3-methoxypropoxy)propan-1-ol Chemical compound COCCCOCCCO QCAHUFWKIQLBNB-UHFFFAOYSA-N 0.000 description 1
- JCLFHZLOKITRCE-UHFFFAOYSA-N 4-pentoxyphenol Chemical compound CCCCCOC1=CC=C(O)C=C1 JCLFHZLOKITRCE-UHFFFAOYSA-N 0.000 description 1
- 241000186427 Cutibacterium acnes Species 0.000 description 1
- 208000001840 Dandruff Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- YAVZHCFFUATPRK-YZPBMOCRSA-N Erythromycin stearate Chemical compound CCCCCCCCCCCCCCCCCC(O)=O.O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 YAVZHCFFUATPRK-YZPBMOCRSA-N 0.000 description 1
- UUOUOERPONYGOS-CLCRDYEYSA-N Fluocinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@H](F)C2=C1 UUOUOERPONYGOS-CLCRDYEYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 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
- 229940124091 Keratolytic Drugs 0.000 description 1
- 206010054107 Nodule Diseases 0.000 description 1
- 206010033733 Papule Diseases 0.000 description 1
- 206010037888 Rash pustular Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- BSUQCLSFQSUNED-PPPRQHODSA-N [(2s,3r,4s,6r)-4-(dimethylamino)-2-[[(3r,4s,5s,6r,7r,9r,11r,12r,13s,14r)-14-ethyl-7,12,13-trihydroxy-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-2,10-dioxo-oxacyclotetradec-6-yl]oxy]-6-methyloxan-3-yl] ethyl car Chemical compound O1[C@H](C)C[C@H](N(C)C)[C@@H](OC(=O)OCC)[C@@H]1O[C@H]1[C@@](O)(C)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@](C)(O)[C@@H](CC)OC(=O)[C@H](C)[C@@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(OC)C2)[C@@H]1C BSUQCLSFQSUNED-PPPRQHODSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960003749 ciclopirox Drugs 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229960003203 erythromycin estolate Drugs 0.000 description 1
- AWMFUEJKWXESNL-JZBHMOKNSA-N erythromycin estolate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O.O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)OC(=O)CC)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AWMFUEJKWXESNL-JZBHMOKNSA-N 0.000 description 1
- 229960000741 erythromycin ethylsuccinate Drugs 0.000 description 1
- NSYZCCDSJNWWJL-YXOIYICCSA-N erythromycin ethylsuccinate Chemical compound O1[C@H](C)C[C@H](N(C)C)[C@@H](OC(=O)CCC(=O)OCC)[C@@H]1O[C@H]1[C@@](O)(C)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@](C)(O)[C@@H](CC)OC(=O)[C@H](C)[C@@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(OC)C2)[C@@H]1C NSYZCCDSJNWWJL-YXOIYICCSA-N 0.000 description 1
- 229960004213 erythromycin lactobionate Drugs 0.000 description 1
- 229960004142 erythromycin stearate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229940043075 fluocinolone Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 150000007928 imidazolide derivatives Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000001530 keratinolytic effect Effects 0.000 description 1
- 125000002669 linoleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229940055019 propionibacterium acne Drugs 0.000 description 1
- 208000029561 pustule Diseases 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 125000001444 retinoyl group Chemical group O=C([*])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C1=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C1(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/602—Glycosides, e.g. rutin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Description
1. t 1 1 Pharmaceutical and cosmetic compositions based on pyridones and
on antibacterial agents 2208149 The present invention relates to new compositions based on pyridone derivatives and on antibacterial agents of the macrolide and the pyranoside family, intended for use in treatments of dermatoses such as acne and in the 5 cosmetic treatment of the skin.
The aetiopathology of acne, although poorly defined, owes its origin to the formation of a characteristic lesion, the comedo. The latter results from the obstruca consequence of dyskerinfundibulum of the duct.
tion of the pilosebaceous duct as atinization of the region of the This obstruction has the major effect of modifying the rheological properties of the sebum, and the physiochemical properties of the medium. This modification leads to the hyperproliferation of the cutaneous resident strains, which trigger an inflammatory type reaction of the body.
Two types of Lesions are generally distinguished.
The first type corresponds to the so-called open comedo or blackhead, the clinical feature of which is commonplace and whose development remains limited. This type of comedo may be readily removed, either by extrusion, or by physical or chemical treatment by the use of topical agents known as keratolytics, which are well known per se.
The second type corresponds, initially, to the cleveLopment of the so-caLLed cLosed comeclones or microcysts, the finaL stage of which is the rupture of the piLosebaceous foLLicLe which has produced it and which reLeases into the clermis numerous infLammatory products in5 clucing reaction of the host body.
The Lesions which characterize infLammatory acne are hence intermediate stages of the microcysts, and are grouped together under the generic names of papuLes, pustuLes, noduLes or cysts, noduLocystic acne represent- ing the most severe form of acne.
At the present time the products which generate the infLammation, or the mechanisms by which they generate the infLammation, remain poorLy defined, aLthough many cLinicaL experiments suggest that the bacteriaL fLora, of which Propionibacterium acnes is the major representative, are strongLy impLicated.
It is known that the topicaL or systemic use of antibiotic compounds, such as erythromycin, cLinclamycin, Lincomycin or their derivatives, in the therapy of acne has as its immediate consequence a very obvious anti-infLammatory effect.
It is thought, moreover, that certain skin yeasts, in particuLar Pityrosporum ovaLe or Pityrosporum orbicuLare yeast, are present in the infLammatory acne Lesions, and it has been shown that Pityrosporum ovaLe was one of the primary causes of certain infLammatory skin conditions such as dandruff (pytiriasis capitis) and seborrheic 1 dermatitis.
During the rupture of the comedo, the Pityrosporum ovale yeast, or its transitory forms, are released and also generate inflammation.
The Applicant has discovered, and this forms the subject of the invention, that by combining pyridone deriv atives and antibacterial agents chosen from macrolide antibiotics and pyranosides, it was unexpectedly possible to improve the treatment of acne.
The Applicant has discovered that the combination of antifungal agents, of the pyridone derivative type, and antibacterial agents mentioned above combats the in flammation due to acne much more rapidly and more effec tively than an antifungal agent alone or an antibacterial agent alone.
The subject of the invention Is hence a pharma- ceutical composition intended for the treatment of acne, combining a pyridone derivative with certain antibacterial agents.
Another subject of the invention consists of the use of the composition defined above for the preparation of a composition for treating acne.
Other subjects of the invention will become apparent on reading the description and the examples which follow.
The composition intended for a topical application for the treatment of acne is essentially characterized in that it contains, in a physiologically acceptable medium, at least one pyridone derivative corresponding to the formula:
H < ']I--R 1 ( I) 4 2 3 in which:
R1 denotes a hydrogen atom, a linear or branched alkyl group having from 1 to 17 carbon atoms, a cycloalkyl group having from 5 to 8 carbon atoms, a cycloalkylalkylene group, the aLkylene group having from 1 to 4 carbon atoms, an aryl group, an aralkyl group, the alkyl group having from 1 to 4 carbon atoms, an arylalkenyl group, the alkenyl group having from 2 to 4 carbon atoms, it being possible for the aryl and cycloalkyl groups to be substituted with an alkyl group having from 1 to 4 carbon atoms or alternatively an alkoxy group having from 1 to 4 carbon atoms; is R2 denotes hydrogen, alkyl having from 1 to 4 carbon atoms, alkenyL having from 2 to 4 carbon atoms, a halogen atom or a benzyl radical; R3 denotes hydrogen, alkyl having from 1 to 4 carbon atoms or phenyl; and 20 R4 denotes hydrogen, alkyl having from 1 to 4 carbon atoms, alkenyl having from 2 to 4 carbon atoms, methoxymethyL or a halogen atom or a benzyl radical, as well as their cosmetically or pharraceutically acceptable salts, and at Least one antibacterial agent chosen from macroLicle antibiotics and pyranosides, as weLL as their saLts or esters.
EspeciaLLy preferred compounds of formuLa (I) are those for which Rl denotes a cycLohexyL group and R3 a Lower aLkyL group, or aLternativeLy those for which Rl denotes a Linear or branched aLkyL group and R3 a Lower aLkyL group. Among these compounds, those which are more especiaLLy preferred are 6-cycLohexyL-1-hydroxy-4-methyL- 2(lH)-pyridone, known as CicLopirox, when it is in the form of an ethanoLamine saLt, and 1-hydroxy-4-methyL-6 (2,4,4-trimethyLpentyL)-2(lH)-pyridone, known as Octopirox, when it is in the form of an ethanoLamine saLt.
EspeciaLLy preferred antibacteriaL agents are chosen from:
erythromycin derivatives, such as erythromycin, its saLts and its esters, and more especiaLLy erythro mycin estoLate, erythromycin ethyLcarbonate, erythromycin ethyLsuccinate, erythromycin gLucoheptonate, erythromycin Lactobionate, erythromycin propionate LauryL suLphate, erythromycin LinoLeate, erythromycin propionate, erythro mycin stearate, monoenic esters such as erythromycin A monooLeate; the cLinclamycin derivatives are the hydrochLoricles, paLmitates and phosphates; and the Lincomycin derivatives are the hydrochLoricles.
A preferred embodiment consists in using erythro mycin retinoates, cLinclamycin retinoates or Lincomycin retinoates as antibacterial agents. Such compounds are, in particular, described in French Patent AppLication No. 86/06,528. The compounds in question are, more especiaLLy, the retinoic esters at the 21-position of erythro- mycin A, and the retinoic esters at the 3-position of Lincomycin and of cLindamycin. The retinoic esters at the 21-position of erythromycin A may be represented by the following formula:
0 H C.. CH 3 3 H 3 C.
H OH OH .-CH3 CH RO N 3 C 11 3 ( I I H r_ CH 2 3.. 0 0 1 CH 3 CH 3 OCH3 CH 3 CH 3 00 n OR' 3 in which R denotes an all-trans-retinoyl radical or a 13-ciz-retinoyt radical and R' denotes H; the retinoyl radical having the formula:
13 11 ( I I I) (ú) (9) (9) C (E) o r is ( z) The retinoic esters at the 3-position of lincomy- cin and of ctindamycin may be represented by the following formulae:
3 CE3 N E 3 H E 11C1 C3H7 3 7 CONIL CORH CK H 0 a EL a HO H H 9 1 H 1 M R TI R 3 30 SCH3 I v) 1 ( v SC:R3 OF.
in which R has the same meaning as that given above.
These compounds may be prepared by various esterification processes, and especially an esterification carried out in an anhydrous organic solvent medium, preferably in tetrahydrofuran alone or mixed with another organic solvent such as pyridine, by reacting an excess of mixed anhydride of carbonic and aLL-trans- or 13-cisretinoic acids (prepared in situ, for example, from ethyl chLoroformate and aLL-trans- or 13-cis- acid) with ery thromycin A, Lincomycin and cLindamycin in base form, in the presence of an organic or inorganic base such as pyridine and/or sodium hydrogen carbonate.
Another esterification process consists, in particuLar for Lincomycin and cLindamycin, in using the imidazoLides of retinoic acids in an anhydrous solvent such as N,N-dimethyLformamide, in the presence of a base 8 such as sodium tert-butytate or potassium tert-butylate, leading to a mixture of retinoic esters of these antibiotics.
Other erythromycin A derivatives described, in particular, in FR-A-2,582,000, are represented by the formula (II), in which R or R' denotes a di- or trienic C18 linear acyl radical of all-cis M stereochemical configuration, and the remaining R or R denotes a hydrogen atom.
According to a preferred embodiment, R or R' denotes the following radicals:
(9Z, 12Z)-octadecadienoyl or linoleoyl (9Z, 12Z, 15Z)-octadecatrienoyl or cL-Linolenoyl, and is (6Z, 9Z, 12Z)-octadecatrienoyl or y-linolenoyl.
21-0-tinoleylerythromycin A, C-D-Linoleylerythromycin A and C-0-QLLinoLey0erythromycin A may be mentioned in particular.
These compositions can also contain other compounds, such as known sjjbstances capable of having an effect on the treatment of acne, and in particular Scarboxymethylcysteine, thiamorphotinone, S-benzyLcysteamine and their derivatives, and tioxolone.
In one embodiment, the compositions according to the invention contain keratolytic agents such as, for example, salicylic acid in proportions from 0.01 to 10% 4 i by weight, benzoyL peroxide in proportions from 0.01 to 10% by weight, resorcinoL in proportions from 0.01 to 5% by weight, retinoic acid and its derivatives, as weLL as humectants such as, for exampLe, gLycerin and urea.
In another embodiment, the compositions aLso contain steroidaL or nonsteroidaL anti-infLammatory agents such as, more especiaLLy, hydrocortisone, inclomethacin, gLycyrrhetinic acid, a-bisaboLoL, betamethasone, fLuocinoLone acetonicle and clesoxymethasone.
The pyriclone derivatives are preferabLy used in proportions from 0.01 to 5% by weight reLative to the totaL weight of the composition, and the antibacteriaL agents in proportions from 0.01 to 5% by weight reLative to the totaL weight of the composition.
Hydrocortisone or inclomethacin, when they are present, are present in proportions aCso of between 0.01 and 5% by weight reLative to the totaL weight of the of the composition.
The compositions according to the invention may be presented in various forms, such as geL, pad, cream, Lotion, spray, foam, powder, ointment, stick, cake or Liquid soap form.
The compositions can aLso contain adjuvants customariLy used in pharmaceuticaL compositions appLied on the 25 skin, and in particuLar water or mixtures of water and soLvents such as Lower aLcohoLs, for exampLe ethanoL or isopropanoL, ethyLene gLycoL, ethyLene gLycoL monomethyL, monoethyl or monobutyl ethers, propylene glycol, propylene glycol monomethyl ether and dipropylene glycol monomethyl ether, antioxidants and thickeners.
The therapeutic treatment of acne according to the invention is preferably carried out according to a process that consists in applying a sufficient quantity of the composition according to the invention two or three times per day on the areas of the skin to be treated, continuing this for a period of 6 to 30 weeks, and prefer- ably 12 to 24 weeks.
The compositions according to the invention can be used preventively, in particular on the areas of skin likely to be affected by acne.
The compositions according to the invention may also be used for the cosmetic treatment of the skin; in particular, they enable comedones to be treated and facilitate extrusion of the latter, and hence cleanse the skin.
The Applicant found that the compositions according to the invention not only enabled a very rapid improve- ment to be obtained in the inflammatory state of acne, but also enabled a decrease to be brought about in the lesions of the so-called first type, the feature of which is that they are non-inflammatory.
The examples which follow are designed to illus- trate the invention, no limitation of the latter being implied.
z - 11 PREPARATION EXAMPLE 1 Preparation of 21-0-(13-cis-retinoyl)erythromycin A 9 (16.6 mmol) of 13-cis-retinoic acid are dis- solved in 35 ml of anhydrous tetrahydrofuran in a round s bottomed flask and under an inert atmosphere; the reaction mixture is cooled to OOC and then 3 mI (38 mmol) of anhydrous pyridine and 1.6 ml (16.6 mmol) of ethyl chloro formate are poured in. The solution is stirred for 5 minutes and 2.5 9 (30 mmol) of sodium hydrogen carbonate are added, followed by 4.9 9 (6.7 mmol) of erythromycin A, previously dissolved in 150 mt of tetrahydrofuran. The reaction inixture is then left with stirring for 10 hours while being allowed to return to room temperature (thin layer chromatography on silica gel: methylene chloride/ methanol, 10%). The solution is poured into 60 mI of water and then extracted with ethyl acetate. The organic phase is dried over magnesium sulphate, filtered and then concentrated under partial vacuum. The crude product thereby obtained is chromatographed on a column of silica gel (HPLC) using the etuant ethyl acetatelhexane (7:3), Leading to the isolation of 4.4 g (65% yield) of pure 21-0-(13-cis- retinoyl)erythromycin A. M.p. 820C (hexanelethyl acetate) [cc] 22 = -170 (C = 6 mg/mI, dichloromethane) D Microanalysis: C57H93NO14 c 67.36 Calculated % M = 1016.4 H N 9.22 1.38 Found %:
67.48 9.32 1.38 Infrared: band at 1735 cm-1 (ester) 13C NMR (CDC13. internal ref. TMS) Negative y effects at the 11-position (-2.2 ppm) and 31-position (-2.1 ppm), indicate the 21-position of the ester. Carbons C20 (20.94 ppm), C"14 (117.28 ppm) and C12 (131.9 ppm) of the retinoic chain are in agree ment with the 13-cis stereochemistry of the retinoic chain.
PREPARATION EXAMPLE 2 is Preparation of 21-0-(all-trans-retinoyl)erythromycin A 9 (16.6 mmol) of all-trans-retinoic acid are dissolved in 35 mI of anhydrous tetrahydrofuran in a roundbottomed flask and under an inert atmosphere, the reaction mixture is cooled to OOC and then 3 mI (38 mmol) of anhydrous pyridine and 1.6 ml (16.6 mmol) of ethyl chloroformate are poured in; the solution is stirred for 5 minutes and 2.5 9 (30 mmol) of sodium hydrogen carbonate are added, followed by 4.9 g (6.7 inmol) of erythromycin A, previously dissolved in 150 ot of tetrahydrofuran. The reaction mixture is then left with stirring for 10 hours while being allowed to return to room temperature (thin layer chromatography on silica get: methylene chloride/ methanol, 1OV. The solution is poured into 60 mI of water and then extracted with ethyl acetate. The organic phase is dried over magnesium sulphate, filtered and then concentrated under partial vacuum. The crude product 1 thereby obtained.is chromatographed on a column of sili gel (HPLC) using the eluant ethyl acetatelhexane (7:3), leading to the isolation of 4.1 9 (60% yield) of pure 21-0-(all-trans-retinoyt)erythromycin A.
[C1122 = -650 (C = 2 mglmt, dichloromethane) D Microanalysis C57H93NO14.4H20; M = 1088.5 C H N Calculated % 62.89 9.35 Found %: 62.91 8.90 13 C NMR (CDC13,, internal ref. TMS) Negative y effects at the V-position (-2 ppm) and 31-position (-1.9 ppm), indicate the 2'-position of the ester. Carbons C"20 (14.1 ppm), C"14 (119. 36 ppm) and C"12 (135.19 ppm) are in agreement with the all- is trans stereochemistry of the retinoic chain. PREPARATION EXAMPLE 3 Preparation of 3-0-(all-trans-retinoyl)ctindamycin 9 (16.6 mmol) of all-trans-retinoic acid are dissolved in 30 mI of anhydrous tetrahydrofuran in a round-bottomed flask and under an inert atmosphere; the reaction mixture is cooled to OOC and then 6 ml (76 mmol) of anhydrous pyridine and 1.6 ml (16.6 mmol) of ethyl chloroformate are poured in; the solution is stirred for 5 minutes and 1.25 9 (15 mmol) of sodium hydrogen carbonate are added, followed by 2.35 9 (5.5 mmol) of clindamycin, previously dissolved in 100 ml of a tetra hydrofuran/pyridine M2) mixture. The reaction mixture 1.29 1.29 14 - 1 5 is is then left with stirring for 10 hours while being allowed to return to room temperature (thin layer chromatography on silica gel: methylene chloridelmethanol 5%). The solution is poured into 80 ml of water and then extracted with ethyl acetate. The organic phase is dried over magnesium sulphate, filtered and then concentrated under partial vacuum. The crude product thereby obtained is chromatographed on a column of silica gel (HPLC) using the eluent ethyl acetatelhexane (5:5), leading to the isolation of 2.15 g (55% yield) of pure 3-0-(alltransretinoyOclindamycin. M.p. 620C [cc] 22 = +500 (C = 100 mglml, dichloromethane) D Microanalysis: C38H59N2SO6C1.2.5H20; M = 752.5 C H N Calculated %:
Found %:
13 60.44 8.08 3.23 60.66 8.57 3.72 C NMR (CDC13. internal ref. TMS): negative effects at the 4-position (-2.8 ppm) and 2-position (-1.9 ppm). The chemical shifts of C"14 (117.84 ppm) and C"20 (14.11 ppm) confirm the all-trans stereochemistry of the retinoyl chain.
PREPARATION EXAMPLE 4 Preparation of 3-0-(13-cis-retinoyl)cli_ndamyein g (16.6 mmol) of 13-cis-retinoic acid are dissolved in 30 ml of anhydrous tetrahydrofuran in a roundbottomed flask and under an inert atmosphere; the reaction 1 Q 1 mixture is cooled to OOC and then 6 ml (76 mmol) of anhydrous pyridine and 1.6 mI (16.6 mmol) of ethyl chloroformate are poured in; the solution is stirred for 5 minutes and 1.25 g (15 mmol) of sodium hydrogen carbonate are added, followed by 2.35 g (5.5 mmol) of clindamycin, previously dissolved in 100 ml of a tetrahydrofuranIpyridine (M) mixture. The reaction mixture is then left with stirring for 10 hours while being allowed to return to room temperature (thin layer chromatography on silica gel; methylene chloridelmethanol 5%). The solution is poured into 80 mI of water and then extracted with ethyl acetate. The organic phase is dried over magnesium sulphate, filtered and then concentrated under partial vacuum. The crude product thereby obtained is chromatographed on a column of silica gel (HPLC) using the eluant ethyl acetate/hexane (5..5), leading to the isolation of 2 9 (51% yield) of pure 3-0-(13-cis-retinoyl)clindawycin. M.p. 950C (hexanelethyl acetate) [C1320 = +1110 (C = 15 inglml, dichtoromethane) D Microanalysis C38H59CIN2S06; M = 707.4 C H Calculated % 64.52 8.41 Found %: 64.47 8.45 13 C NMR (CDC13,, internal ref. TMS) The position of the ester is indicated by the positive B effect at the 3- position (+1.77 ppm) and the k - 16 negative y effects at the 2-position (-1.4 ppm) and 4-position (-2.5 ppm). The 13-cis configuration is con firmed by C20 (20.93 ppm) and C"14 (115.94 ppm).
PREPARATION EXAMPLE 5 Preparation of 3-0-(13-cis-retinoyl)tincomycin 9 (16.6 mmol) of 13-cis-retinoic acid are dis solved in 30 mt of anhydrous tetrahydrofuran in a round bottomed flask under an inert atmosphere; the reaction mixture is cooled to OOC and then 6 mt (76 mmol) of anhydrous pyridine and 1.6 mI (16.6 mmol) of ethyl chloroformate are poured in; the solution is stirred for 5 minutes and 1.25 9 (15 mmol) of sodium hydrogen carbonate are added, followed by 2.2 9 (5.4 mmol) of lincomycin, previously dissolved in 100 mI of a tetrahydrofuranIpyridin (7:3) mixture. The reaction mixture is then left with stirring for 10 hours while being allowed to return to room temperature (thin layer chromatography on silica gel: methylene chloridelmethanol, 10%). The solution is poured into 100 ml of water and then extracted with ethyl acetate. The organic phase is dried over magnesium sulphate, filtered and then concentrated under partial vacuum. The crude product thereby obtained is chromatographed on a column of silica gel (HPLC) using the eluant ethyl acetatelhexane (8:2), leading to the isolation of 1.85 g (50% yield) of pure 3-0-(13-cis-retinoyl)lincomycin. M.p. 950 (hexanelethyl acetate) ECL120 = +1030 (C = 7 mgImI, dichloromethane) D Microanalysis c38H6ON2S07-2-SH20; M = 734.5 c H Calculated % 62.18 9.03 Found %: 62.33 8.64 13C NMR (CDC13.. internal ref. TMS) The position of the ester is indicated by the positive $ effect at the 3- position (+1.6 ppm) and the negative y effects at the 2-position (-2.4 ppm) and 4-position (-1.9 PPm). The 13-cis configuration is con- firmed by C20 (20.98 ppm) and C14 (115.83 ppm).
PREPARATION EXAMPLE 6 Preparation of a mixture of 7-0-(all-trans-retinoyl)lin:
comycin, 3-0-(all-trans-retinoyl)lincomycin and 2-0-(atl-trans-retinoyt)lincomycin monoesters 9 (74 mmol) of Lincomycin are dissolved in 300 ml of anhydrous N,N-dimethylformamide in a round bottomed fLask and under an inert atmosphere, 830 mg (7.4 amol) of potassium tert-butylate are then added and stirring is continued at room temperature for 90 minutes.
A solution of 13 9 (37 mool) of 1-(all-trans-retinoyl)imi dazote in 150 mL of N,N-dimethylformamide is then poured in and the resulting mixture is stirred at room temperat ure for 12 hours (thin layer chromatography on silica gel: methylene chloridelmethanol, 7.5%). The solution is poured into 500 mt of water and then extracted with ethyl acetate. The organic phase is dried over magnesium sulphate, filtered and then concentrated under partial vacuum.
The crude product thereby obtained is chromatographed on a column of silica gel (HPLC) using the eluant ethyl acetate/hexane (7:3), leading to the isolation of 39 g (77%) of a mixture of all-trans-retinoic monoesters of 5 Lincomycin at the 2-, 3- and 7-positions. 13C NMR (CDC13.. internal ref. TMS) - Negative y effects at the 8-position (-2.5 ppm) and the 6position (-3.8 ppm) indicate the site of esterification of a monoester at the 7-position, - Negative y effect at the 1-position (-4 ppm) indicates the monoester at the 2-position, and negative y effects at the 2-position (-2 ppm) and 4-position (-2.6 ppm) indicate the position of the monoester at the 3-position. The positions of Cl are at 85.06 ppm for the 2monoester, is at-88.45 ppm for the 7-monoester and at 89.67 ppm for the monoester at the 3-position. The all-trans configuration of the retinoic chain is indicated for C14 at 117.78 ppm and for C20 at 14.08 ppm; a trace of isomerization is noted by the pres20 ence of a peak at 115.2 ppm W'14) indicating the 13-cis isomer.
PREPARATION EXAMPLE 7 Preparation of a mixture of 2-0-(all-transretinoyl)clindamycin, 3-0-(all-trans-retinoyl)clindamycin and 4-0-(alltrans-retinoyl)clindamycin monoesters 20 9 (47 mmol) of clindamycin are dissolved in 250 ml of an anhydrous N,N-dimethytformamide in a round- It 19 bottomed flask and under an inert atmosphere, and 527 mg (4.7 mmol) of potassium tert-butylate are then added to the reaction medium, which is then stirred at room temperature for 90 minutes. A solution of 8.250 9 (23.5 mmot) of 1-(all-trans-retinoyl)imidazole in 150 mt of anhydrous N.Ndimethytformamide is then poured in and the resulting medium is stirred at room temperature for 12 hours (thin Layer chromatography on silica gel: methylene chloride/ methanol, 5%). The solution is then poured into 500 ml of water, after which it is extracted with ethyl acetate. The organic phase is dried over magnesium sulphate, fittered and then concentrated under partial vacuum. The crude product thereby obtained is chromatographed on a column of silica get (HPLC) using the eluant ethyl acetate/ hexane (5:5), Leading to the isolation of 28 g (85%) of a mixture of all-trans-retinoic monoesters of clindamycin at the 2-, 3- and 4-positions. 13 C NMR (C0C13. internal ref. TMS) ' - Negative y effect at the 1-position (-3 ppm) indicates the 2-position of the ester, - Negative y effects at the 4-position (-2.8 ppm) and 2-position (-1.9 ppm) indicate the monoester at the 3 posi tion, and weak negative y effect at the 3-position indicates the monoester at the 4-position.
The positions of Cl are at 84.63 ppm for the 2-monoester, at 88.79 ppm for the 3-monoester and at 87.98 ppm for the 4-monoester.
The all-trans configuration of the retinoic chain is predominant (C"14 at 117.5 ppm and C20 at 14.08 ppm), but there are clear traces of isomerization, in particular at C20 and C14.
EXAMPLE 1 ANTI-ACNE LOTION The following composition is prepared:
Erythromycin Octopirox Butylated hydroxytoluene (SHT)Ibutylated hydroxyanisole (SHA) antioxidant Water/isopropanol solution (60:40 by volume) qs EXAMPLE 2
ANTI-ACNE LOTION The following composition is prepared:
Clindamycin Octopirox Senzoyl peroxide Antioxidant (SHT, SHA) Waterlethanot solution (60:40 by volume) h c 2 9 1 9 0.4 9 9 0.6 9 0.02 g 2.5 g 0.1 g 9 l, - 21 EXAMPLE 3 ANTI-ACNE GEL The foLLowing composition is prepared: Erythromycin SaLicyLic acid Octopirox PoLyacryLic acid crossLinked with a poLyfunctionaL agent, soLd by the company S.F. GOODRICH under the trade name "CARBOPOL 941" Antioxiclant (BHT, BHA) EthanoL Water EXAMPLE 4 q s GEL The foLLowing composition is prepared:
Erythromycin LinoLeate CycLopirox HydroxypropyL ceLLuLose soLd by the company HERCULES under the trade name "KLUCEL H" Antioxiclant (BHT, BHA) EthanoL Water qs 2 9 0.5 g 2 9 0.5 g 0.5 9 9 9 3 9 1 9 1 9 0.1 g 9 9
Claims (21)
1. A composition suitable for topical application which comprises, in a physiologically acceptable medium, at least one pyridone derivative corresponding to the formula:
R1 R2 3 in which:
(I) R, denotes hydrogen, linear or branched alkyl having from 1 to 17 carbon atoms, cycloalkyl having from 5 to 8 carbon atoms, cycloalkylalkylene, in which the alkylene group has from 1 to 4 carbon atoms, aryl, aralkyl in which the alkyl group has from 1 to 4 carbon atoms, arylalkenyl in which the alkenyl group has from 2 to 4 carbon atoms, such that the aryl and cycloalkyl groups can be substituted by an alkyl or alkoxy group having from 1 to 4 carbon atoms; R 2 denotes hydrogen, alkyl having from 1 to 4 carbon atoms, alkenyl having from 2 to 4 carbon atoms, halogen or benzyl; R 3 denotes hydrogen, alkyl having from 1 to 4 carbon atoms or phenyl; and R., denotes hydrogen, alkyl having from 1 to 4 carbon atoms, alkenyl having from 2 to 4 carbon atoms, methoxymethyl halogen, or a benzyl radical; or a cosmetically or pharmaceutically acceptable salt thereof, and at least one 7 antibacterial agent which is a macrolide antibiotic or pyranoside, or a salt or ester thereof.
2. A composition according to claim 1, in which R, denotes a cyclohexyl or linear or branched alkyl group and R 3 denotes a lower alkyl group, for example of 1 to 6 carbon atoms.
3. A composition according to claim 1 or 2, in which the compound of formula (I) is 6-cyclohexyl-1-hydroxy4-methyl-2(1H)-pyridone or 1-hydroxy4-methyl-6-(2,4,4- trimethylpentyl)-2(1H)-pyridone.
4. A composition according to any one of claims 1 to 3, in which the antibacterial agent is an erythromycin, clindamycin or lincomycin derivative.
5. A composition according to claim 4, in which the erythromycin derivative is erythromycin or an estolate, ethylcarbonate, ethylsuccinate, glucoheptonate, lactobionate, propionate lauryl sulphate, propionate, stearate, linoleate or monoenic, di- or trienic ester of erythromycin.
6. A composition according to claim 4, in which the clindamycin derivative is a hydrochloride, palmitate or phosphate, and the lincomycin derivative is lincomycin hydrochloride.
7. A composition according to any one of claims 1 to 6, in which the antibacterial agent is an erythromycin retinoate, clindamycin retinoate or lincomycin retinoate.
8. A composition according to any one of claims 1 to 7 which also contains a keratolytic agent.
9. A composition according to claim 8, in which the keratolytic agent is benzoyl peroxide, salicylic acid or resorcinol.
10. A composition according to any one of claims 1 to 9 which also contains S-carboxymethyl-cysteine, thiamorpholinone, S-benzylcysteamine or a derivative thereof or tioxolone.
11. A composition according to any one of claims 1 to 10 which also contains at least one steroidal or nonsteroidal anti- inflammatory agent.
12. A composition according to claim 11, in which the anti-inflammatory agent is hydrocortisone, indomethacin, glycyrrhetinic acid, m-bisabolol, betamethasone, fluocinolone acetonide or desoxymethasone.
13. A composition according to any one of claims 1 to 12, in which the compound of formula (I) is present in an amount from 0.01 to 5% by weight, and in that the antibacterial agent is present in an amount from 0.01 to 5% by weight, relative to the total weight of the composition.
14. A composition according to any one of claims 1 to 13 which is in the form of a gel, pad, cream, lotion, spray, ointment or stick. 25
15. A composition according to any one of claims 1 to 14 which contains water or a mixture of water and a 1 - lower alcohol, glycol or glycol ether.
16. A composition according to any one of claims 1 to 15 which also contains one or more thickening agents, antioxidants, colouring agents or perfumes.
17. A composition according to any one of claims 1 to 16, formulated for use in the therapeutic treatment of acne.
18. A composition according to any one of claims 1 to 16, formulated for use in the cosmetic treatment of the 10 skin.
19. A composition according to claim 1 substantially as described in any one of Examples 1 to 4.
20. Use of the composition as defined in any one of claims 1 to 19, for the preparation of a medicinal product 15 intended for treating acne.
21. Process for cosmetic treatment which comprises applying to the area to be treated a composition as defined in any one of claims 1 to 19.
1 Published 1988 at The Paten-. Off-.e. State Ho:sc. 66 71 HiC'.'Ho.
bcrr.. London WCIR 4TF Purther cc;,c- may be obtained frc;r,, Tr.e Patent Officc Sales Branch. St Ma-3, Cray. Orpingtcr.. Kent BR5 3RD. Printed by Multiplex techniques ltd, S-, Ma:T Cray. Kent. Con. 1187
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
LU86945A LU86945A1 (en) | 1987-07-17 | 1987-07-17 | PHARMACEUTICAL AND COSMETIC COMPOSITIONS BASED ON PYRIDONES AND ANTIBACTERIAL AGENTS |
Publications (3)
Publication Number | Publication Date |
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GB8816916D0 GB8816916D0 (en) | 1988-08-17 |
GB2208149A true GB2208149A (en) | 1989-03-08 |
GB2208149B GB2208149B (en) | 1991-10-09 |
Family
ID=19730948
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GB8816916A Expired - Lifetime GB2208149B (en) | 1987-07-17 | 1988-07-15 | Pharmaceutical and cosmetic compositions based on pyridones and on antibacterial agents |
Country Status (6)
Country | Link |
---|---|
BE (1) | BE1002690A4 (en) |
CH (1) | CH674930A5 (en) |
FR (1) | FR2618072B1 (en) |
GB (1) | GB2208149B (en) |
IT (1) | IT1223695B (en) |
LU (1) | LU86945A1 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4906454A (en) * | 1989-02-23 | 1990-03-06 | The Procter & Gamble Company | Deodorant compositions containing specific piroctone salts and perfumes |
US5487884A (en) * | 1987-10-22 | 1996-01-30 | The Procter & Gamble Company | Photoprotection compositions comprising chelating agents |
WO1998013042A1 (en) * | 1996-09-27 | 1998-04-02 | Hoechst Aktiengesellschaft | Antimycotic gel with high active substance release |
WO1998013043A1 (en) * | 1996-09-27 | 1998-04-02 | Hoechst Aktiengesellschaft | Use of 1-hydroxy-2-pyridones for the treatment of skin diseases |
EP0909174A1 (en) * | 1996-03-26 | 1999-04-21 | The Regents Of The University Of California | TREATMENT OF CYSTIC DISEASE WITH TNF-$g(a) |
US6455551B1 (en) | 1996-10-30 | 2002-09-24 | Aventis Pharma Deutschland Gmbh | Use of 1-hydroxy-2-pyridones for treating mucosa diseases which are difficult to treat |
US7981909B2 (en) | 1996-09-27 | 2011-07-19 | Medicis Pharmaceutical Corporation | Use of 1-hydroxy-2-pyridones for the treatment of seborrheic dermatitis |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3830509A1 (en) * | 1988-09-08 | 1990-03-22 | Hoechst Ag | MEDICINAL PRODUCTS WITH SYNERGISTIC ANTIMYCOTIC AND ANTIVIRAL EFFECTIVENESS |
FR2685638A1 (en) * | 1991-12-31 | 1993-07-02 | Biorga Sa Laboratoires | Compositions for cosmetic and/or dermatological use, comprising a combination of pyrithione zinc, piroctone olamine and a derivative of collagen and of fatty acid |
FR2722689B1 (en) * | 1994-07-20 | 1996-10-04 | Fabre Pierre Dermo Cosmetique | NOVEL COMBINATION PRODUCT COMPRISING AN ANTIFUNGAL AGENT AND CROTAMITON AS A POTENTIALIZER OF THE ACTIVITY OF THE ANTIFUNGAL AGENT, AND DERMATOLOGICAL AND / OR COSMETIC COMPOSITIONS COMPRISING THE SAME |
DE19917548A1 (en) * | 1999-04-19 | 2000-10-26 | August Wolff Gmbh & Co Arzneim | Stable topical pharmaceutical composition for treating skin diseases, especially acne, contains erythromycin higher fatty acid salt in liquid or viscous carrier |
ITMI20061770A1 (en) * | 2006-09-18 | 2008-03-19 | Carlo Ghisalberti | COSMETIC METHOD OF REDUCING EYES |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2448903A1 (en) * | 1979-02-19 | 1980-09-12 | Martin Henri | Fast acting antimicrobial compsns. - contg. antimicrobial, enzyme, antiinflammatory, and opt. local anaesthetic, keratolytic, mucolytic and emulsifier |
US4299826A (en) * | 1979-10-12 | 1981-11-10 | The Procter & Gamble Company | Anti-acne composition |
DE3140954A1 (en) * | 1981-10-15 | 1983-05-05 | Hoechst Ag | Use of 1-hydroxy-2-pyridones for the prophylaxis and treatment of acne |
GB8524508D0 (en) * | 1985-10-04 | 1985-11-06 | Beecham Group Plc | Composition |
-
1987
- 1987-07-17 LU LU86945A patent/LU86945A1/en unknown
-
1988
- 1988-07-11 FR FR8809408A patent/FR2618072B1/en not_active Expired - Lifetime
- 1988-07-14 CH CH2700/88A patent/CH674930A5/fr not_active IP Right Cessation
- 1988-07-15 BE BE8800826A patent/BE1002690A4/en not_active IP Right Cessation
- 1988-07-15 GB GB8816916A patent/GB2208149B/en not_active Expired - Lifetime
- 1988-07-15 IT IT67667/88A patent/IT1223695B/en active
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5487884A (en) * | 1987-10-22 | 1996-01-30 | The Procter & Gamble Company | Photoprotection compositions comprising chelating agents |
US4906454A (en) * | 1989-02-23 | 1990-03-06 | The Procter & Gamble Company | Deodorant compositions containing specific piroctone salts and perfumes |
EP0909174A1 (en) * | 1996-03-26 | 1999-04-21 | The Regents Of The University Of California | TREATMENT OF CYSTIC DISEASE WITH TNF-$g(a) |
EP0909174A4 (en) * | 1996-03-26 | 2003-01-22 | Univ California | Treatment of cystic disease with tnf-alpha |
WO1998013042A1 (en) * | 1996-09-27 | 1998-04-02 | Hoechst Aktiengesellschaft | Antimycotic gel with high active substance release |
WO1998013043A1 (en) * | 1996-09-27 | 1998-04-02 | Hoechst Aktiengesellschaft | Use of 1-hydroxy-2-pyridones for the treatment of skin diseases |
JP2001501609A (en) * | 1996-09-27 | 2001-02-06 | ヘキスト・アクチエンゲゼルシヤフト | Antifungal gel with high active compound release |
US6469033B1 (en) | 1996-09-27 | 2002-10-22 | Aventis Pharma Deutschland Gmbh | Use of 1-hydroxy-2-pyridones for the treatment of skin diseases |
US7018656B2 (en) | 1996-09-27 | 2006-03-28 | Aventis Pharma Deutschland Gmbh | Antimycotic gel with high active substance release |
US7026337B2 (en) | 1996-09-27 | 2006-04-11 | Aventis Pharma Deutschland Gmbh | Antimycotic gel having high active compound release |
US7981909B2 (en) | 1996-09-27 | 2011-07-19 | Medicis Pharmaceutical Corporation | Use of 1-hydroxy-2-pyridones for the treatment of seborrheic dermatitis |
US6455551B1 (en) | 1996-10-30 | 2002-09-24 | Aventis Pharma Deutschland Gmbh | Use of 1-hydroxy-2-pyridones for treating mucosa diseases which are difficult to treat |
Also Published As
Publication number | Publication date |
---|---|
BE1002690A4 (en) | 1991-05-07 |
IT1223695B (en) | 1990-09-29 |
GB8816916D0 (en) | 1988-08-17 |
IT8867667A0 (en) | 1988-07-15 |
LU86945A1 (en) | 1989-03-08 |
FR2618072A1 (en) | 1989-01-20 |
GB2208149B (en) | 1991-10-09 |
CH674930A5 (en) | 1990-08-15 |
FR2618072B1 (en) | 1993-10-15 |
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Legal Events
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PE20 | Patent expired after termination of 20 years |
Expiry date: 20080714 |