DE2463138C2 - Das Antibiotikum Cyclosporin B (S 7481/F-2), seine Herstellung und Verwendung - Google Patents
Das Antibiotikum Cyclosporin B (S 7481/F-2), seine Herstellung und VerwendungInfo
- Publication number
- DE2463138C2 DE2463138C2 DE2463138A DE2463138A DE2463138C2 DE 2463138 C2 DE2463138 C2 DE 2463138C2 DE 2463138 A DE2463138 A DE 2463138A DE 2463138 A DE2463138 A DE 2463138A DE 2463138 C2 DE2463138 C2 DE 2463138C2
- Authority
- DE
- Germany
- Prior art keywords
- methanol
- liters
- cyclosporin
- fractions
- chloroform
- 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.)
- Expired
Links
- 230000003115 biocidal effect Effects 0.000 title claims description 16
- UCOQITKXMNKTKF-MXGZYYNMSA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28,30-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23 Chemical compound C\C=C\C[C@@H](C)[C@@H](O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](C)NC1=O UCOQITKXMNKTKF-MXGZYYNMSA-N 0.000 title claims description 10
- 238000004519 manufacturing process Methods 0.000 title description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 30
- 239000000843 powder Substances 0.000 claims description 3
- 238000001819 mass spectrum Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims 1
- 238000002844 melting Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 235000015097 nutrients Nutrition 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 241000228245 Aspergillus niger Species 0.000 description 10
- 239000000284 extract Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
- 229920001817 Agar Polymers 0.000 description 7
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 7
- 239000008272 agar Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 241001149960 Tolypocladium inflatum Species 0.000 description 6
- 208000025865 Ulcer Diseases 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 6
- 229930105110 Cyclosporin A Natural products 0.000 description 5
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 5
- 108010036949 Cyclosporine Proteins 0.000 description 5
- 208000009386 Experimental Arthritis Diseases 0.000 description 5
- 229910000831 Steel Inorganic materials 0.000 description 5
- 206010003246 arthritis Diseases 0.000 description 5
- 229960001265 ciclosporin Drugs 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 239000010959 steel Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 210000002683 foot Anatomy 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 206010042674 Swelling Diseases 0.000 description 3
- 240000008042 Zea mays Species 0.000 description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 238000005273 aeration Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000005822 corn Nutrition 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000011888 foil Substances 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 229960002895 phenylbutazone Drugs 0.000 description 3
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 239000011573 trace mineral Substances 0.000 description 3
- 235000013619 trace mineral Nutrition 0.000 description 3
- 241000875119 Cylindrocarpon lucidum Species 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 241000364057 Peoria Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 238000005191 phase separation Methods 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000036269 ulceration Effects 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- FWMBRFVXLUJFCT-WKHWYDSQSA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-30-ethyl-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,25,28-octamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20 Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O FWMBRFVXLUJFCT-WKHWYDSQSA-N 0.000 description 1
- 125000000349 (Z)-3-carboxyprop-2-enoyl group Chemical group O=C([*])/C([H])=C([H])\C(O[H])=O 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- WHBHBVVOGNECLV-OBQKJFGGSA-N 11-deoxycortisol Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 WHBHBVVOGNECLV-OBQKJFGGSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- FWMBRFVXLUJFCT-UHFFFAOYSA-N Cyclosporin U Natural products CCC1NC(=O)C(C(O)C(C)CC=CC)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O FWMBRFVXLUJFCT-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 238000002768 Kirby-Bauer method Methods 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000534579 Persoonia Species 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241001149964 Tolypocladium Species 0.000 description 1
- 241000123975 Trichoderma polysporum Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000000274 adsorptive effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- -1 corn steep liquor Chemical compound 0.000 description 1
- 238000005238 degreasing Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- AAGXMFJYCDONRN-UHFFFAOYSA-N dialuminum oxygen(2-) toluene Chemical compound C1(=CC=CC=C1)C.[O-2].[Al+3].[O-2].[O-2].[Al+3] AAGXMFJYCDONRN-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 244000059217 heterotrophic organism Species 0.000 description 1
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000001965 potato dextrose agar Substances 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 108010009004 proteose-peptone Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 239000001052 yellow pigment Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K4/00—Peptides having up to 20 amino acids in an undefined or only partially defined sequence; Derivatives thereof
- C07K4/06—Peptides having up to 20 amino acids in an undefined or only partially defined sequence; Derivatives thereof from fungi
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/062—Ascomycota
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/14—Fungi; Culture media therefor
- C12N1/145—Fungal isolates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/645—Fungi ; Processes using fungi
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/645—Fungi ; Processes using fungi
- C12R2001/885—Trichoderma
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Pharmacology & Pharmacy (AREA)
- Botany (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medical Informatics (AREA)
- Biomedical Technology (AREA)
- Alternative & Traditional Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Compounds Of Unknown Constitution (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1711173A CH589716A5 (en) | 1973-12-06 | 1973-12-06 | Antibiotics S 7481-F-1 and 2 - prepd. from new strains of Cylindrocarbon or Trichoderma esp. useful as immunosuppressant |
| CH1404374A CH603790A5 (en) | 1974-10-21 | 1974-10-21 | Antibiotics S 7481-F-1 and 2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2463138C2 true DE2463138C2 (de) | 1984-07-05 |
Family
ID=25713544
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2463138A Expired DE2463138C2 (de) | 1973-12-06 | 1974-11-26 | Das Antibiotikum Cyclosporin B (S 7481/F-2), seine Herstellung und Verwendung |
| DE2455859A Expired DE2455859C2 (de) | 1973-12-06 | 1974-11-26 | Das Antibiotikum Cyclosporin A (S 7481/F-1), seine Herstellung und Verwendung |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2455859A Expired DE2455859C2 (de) | 1973-12-06 | 1974-11-26 | Das Antibiotikum Cyclosporin A (S 7481/F-1), seine Herstellung und Verwendung |
Country Status (19)
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH614931A5 (enrdf_load_stackoverflow) * | 1975-11-04 | 1979-12-28 | Sandoz Ag | |
| US4117118A (en) * | 1976-04-09 | 1978-09-26 | Sandoz Ltd. | Organic compounds |
| FI65914C (fi) * | 1978-03-07 | 1984-08-10 | Sandoz Ag | Foerfarande foer framstaellning av farmaceutiska kompositionerinnehaollande cyklosporin a |
| SE448386B (sv) * | 1978-10-18 | 1987-02-16 | Sandoz Ag | Nya cyklosporinderivat, forfarande for framstellning av dem samt farmaceutisk komposition innehallande dem |
| US4396542A (en) | 1980-02-14 | 1983-08-02 | Sandoz Ltd. | Method for the total synthesis of cyclosporins, novel cyclosporins and novel intermediates and methods for their production |
| DE3167014D1 (en) * | 1980-02-14 | 1984-12-13 | Sandoz Ag | A method for the total synthesis of cyclosporins and novel cyclosporins |
| EP0056782B1 (en) | 1981-01-09 | 1984-08-01 | Sandoz Ag | Novel cyclosporins |
| GB8717300D0 (en) * | 1987-07-22 | 1987-08-26 | Nat Res Dev | Cyclosporins |
| ES2095926T5 (es) | 1990-11-02 | 2001-02-16 | Novartis Ag | Cyclosporins. |
| DE69222150T2 (de) * | 1991-01-25 | 1998-01-15 | Fujisawa Pharmaceutical Co | Prozess zur produktion von cyclosporin-a und/oder c |
| KR100304324B1 (ko) * | 1994-10-13 | 2001-11-22 | 김용규 | 사이클로스포린a의제조방법 |
| ES2177652T3 (es) | 1994-11-03 | 2002-12-16 | Novartis Ag | Nuevas formas de preparacion de ciclosporina para la aplicacion oral con composicion simple y alta biodisponibilidad, y procedimiento para su obtencion. |
| US6423233B1 (en) | 2000-08-15 | 2002-07-23 | Biogal Gyogyszergyar Rt. | Purification process |
| WO2004082629A2 (en) | 2003-03-17 | 2004-09-30 | Albany Molecular Research, Inc. | Novel cyclosporins |
| WO2006039164A2 (en) | 2004-09-29 | 2006-04-13 | Amr Technology, Inc. | Novel cyclosporin analogues and their pharmaceutical uses |
| WO2006039163A2 (en) | 2004-09-29 | 2006-04-13 | Amr Technology, Inc. | Cyclosporin alkyne analogues and their pharmaceutical uses |
| WO2006041631A2 (en) | 2004-10-06 | 2006-04-20 | Amr Technology, Inc. | Novel cyclosporin alkynes and their utility as pharmaceutical agents |
| US7696166B2 (en) | 2006-03-28 | 2010-04-13 | Albany Molecular Research, Inc. | Use of cyclosporin alkyne/alkene analogues for preventing or treating viral-induced disorders |
| US7696165B2 (en) | 2006-03-28 | 2010-04-13 | Albany Molecular Research, Inc. | Use of cyclosporin alkyne analogues for preventing or treating viral-induced disorders |
| EP2151450A1 (de) | 2008-07-29 | 2010-02-10 | Sandoz AG | Verfahren zur Aufarbeitung von mikrobiologisch hergestellten zyklischen Oligopeptiden |
-
1974
- 1974-11-26 DE DE2463138A patent/DE2463138C2/de not_active Expired
- 1974-11-26 DE DE2455859A patent/DE2455859C2/de not_active Expired
- 1974-11-27 DK DK617074AA patent/DK136780B/da unknown
- 1974-11-27 FI FI743434A patent/FI52851C/fi active
- 1974-11-28 NO NO744292A patent/NO744292L/no unknown
- 1974-11-29 SE SE7415027A patent/SE423720B/xx not_active IP Right Cessation
- 1974-12-02 NL NLAANVRAGE7415682,A patent/NL179220C/xx not_active IP Right Cessation
- 1974-12-02 GB GB52013/74A patent/GB1491509A/en not_active Expired
- 1974-12-04 ES ES432559A patent/ES432559A1/es not_active Expired
- 1974-12-04 IE IE2502/74A patent/IE40549B1/xx not_active IP Right Cessation
- 1974-12-04 IL IL46180A patent/IL46180A/xx unknown
- 1974-12-04 NZ NZ176117A patent/NZ176117A/xx unknown
- 1974-12-04 DD DD182775A patent/DD115695A5/xx unknown
- 1974-12-04 AU AU76081/74A patent/AU500889B2/en not_active Expired
- 1974-12-05 CA CA215,287A patent/CA1030469A/en not_active Expired
- 1974-12-05 JP JP13893874A patent/JPS5615235B2/ja not_active Expired
- 1974-12-05 FR FR7439877A patent/FR2253531B1/fr not_active Expired
-
1977
- 1977-04-15 FI FI771201A patent/FI54606C/fi not_active IP Right Cessation
- 1977-04-22 PH PH19702A patent/PH13773A/en unknown
-
1980
- 1980-09-25 HK HK538/80A patent/HK53880A/xx unknown
-
1981
- 1981-12-30 MY MY203/81A patent/MY8100203A/xx unknown
Non-Patent Citations (1)
| Title |
|---|
| NICHTS-ERMITTELT * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2463138C2 (de) | Das Antibiotikum Cyclosporin B (S 7481/F-2), seine Herstellung und Verwendung | |
| DE69422526T2 (de) | Polyzyklische antiparasitäre derivate, verfahren und stamm zu ihrer herstellung und ihrer verwendung | |
| DE3051175C2 (enrdf_load_stackoverflow) | ||
| DE68910213T2 (de) | Antibiotikum R106. | |
| CH619735A5 (enrdf_load_stackoverflow) | ||
| DE3109335C2 (de) | Ebelacton A und B, Verfahren zu deren Herstellung und diese Verbindungen enthaltende pharmazeutische Mittel | |
| DE60006690T2 (de) | Antibiotische caprazamycine und verfahren zu deren herstellung | |
| DE2911353C2 (enrdf_load_stackoverflow) | ||
| CH668974A5 (de) | Antitumor-antibiotikum. | |
| DE2004686C3 (de) | Makrolid-Antibioticum SF-837 und dessen Diacetylderivat und deren pharmakologisch nichtgiftige Säureanlagerungssalze sowie Verfahren zur Herstellung des Antibioticums SF-837 | |
| DE2028403B2 (de) | Pepstatin | |
| DD252116A5 (de) | Verfahren zur bekaempfung von pflanzennematoden | |
| CH634853A5 (de) | Schwefelhaltige metabolite, ihre herstellung und verwendung in arznei- und futtermitteln. | |
| DE69620928T2 (de) | Physiologisch aktive Substanzen PF1092A, PF1092B, und PF1092C, Verfahren zu deren Herstellung, sowie diese als aktive Bestandteile enthaltende empfängnisverhütende Mittel und Antikrebsmittel | |
| CH637123A5 (en) | Monocyclic peptide, its preparation and use | |
| DE69718141T2 (de) | Fungizid | |
| DE69214737T2 (de) | Antibiotika NK374186A, NK374186B, NK374186B3 und NK374186C3, Verfahren zu ihrer Herstellung und ihre Verwendung | |
| DE2316429A1 (de) | Verfahren zur herstellung eines neuen metaboliten | |
| CH589716A5 (en) | Antibiotics S 7481-F-1 and 2 - prepd. from new strains of Cylindrocarbon or Trichoderma esp. useful as immunosuppressant | |
| AT350716B (de) | Verfahren zur herstellung neuer antibiotika | |
| DE2039990C2 (de) | Neue Antibiotika B-5050 A bis F (Maridomycin I bis VI), Verfahren zu ihrer Herstellung und ihre pharmazeutische Zubereitung | |
| CH629531A5 (en) | Process for the preparation of the antibiotic A-30912 mixture and of factors A, B, C, D, E, F and G in this antibiotic mixture | |
| EP0546475A1 (de) | Biologisch aktives Pseurotin A und D, neue Metabolite aus Aspergillus fumigatus, Verfahren zu ihrer Herstellung und ihre Verwendung als Apomorphin Antagonisten | |
| DE1695830C3 (de) | Zygosporin A, Verfahren zu seiner Herstellung und diese Verbindung enthaltendes Arzneimittel | |
| DE2825618A1 (de) | Neue antibiotika, ihre herstellung und verwendung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AC | Divided out of |
Ref country code: DE Ref document number: 2455859 Format of ref document f/p: P |
|
| Q172 | Divided out of (supplement): |
Ref country code: DE Ref document number: 2455859 |
|
| 8181 | Inventor (new situation) |
Free format text: HAERRI, EUGEN, DR., 4106 THERWIL, CH RUEEGGER, ARTUR, DR., 4103 BOTTMINGEN, CH |
|
| AC | Divided out of |
Ref country code: DE Ref document number: 2455859 Format of ref document f/p: P |
|
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |