JP2003515579A - 高純度デフェロキサミン・メシレート塩の製造のための多段階プロセス - Google Patents
高純度デフェロキサミン・メシレート塩の製造のための多段階プロセスInfo
- Publication number
- JP2003515579A JP2003515579A JP2001541852A JP2001541852A JP2003515579A JP 2003515579 A JP2003515579 A JP 2003515579A JP 2001541852 A JP2001541852 A JP 2001541852A JP 2001541852 A JP2001541852 A JP 2001541852A JP 2003515579 A JP2003515579 A JP 2003515579A
- Authority
- JP
- Japan
- Prior art keywords
- deferoxamine
- mesylate
- eluent
- acetonitrile
- water
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 76
- IDDIJAWJANBQLJ-UHFFFAOYSA-N desferrioxamine B mesylate Chemical class [H+].CS([O-])(=O)=O.CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN IDDIJAWJANBQLJ-UHFFFAOYSA-N 0.000 title claims description 51
- 238000004519 manufacturing process Methods 0.000 title description 4
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 claims abstract description 183
- 239000012458 free base Substances 0.000 claims abstract description 58
- 239000003480 eluent Substances 0.000 claims abstract description 52
- 229920005989 resin Polymers 0.000 claims abstract description 45
- 239000011347 resin Substances 0.000 claims abstract description 45
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims abstract description 42
- 239000000203 mixture Substances 0.000 claims abstract description 40
- 238000001179 sorption measurement Methods 0.000 claims abstract description 20
- 238000001556 precipitation Methods 0.000 claims abstract description 16
- 229940098779 methanesulfonic acid Drugs 0.000 claims abstract description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 87
- 239000000243 solution Substances 0.000 claims description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 23
- 239000012296 anti-solvent Substances 0.000 claims description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 18
- 239000000725 suspension Substances 0.000 claims description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 13
- 239000003456 ion exchange resin Substances 0.000 claims description 13
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 13
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical group [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 12
- 239000003463 adsorbent Substances 0.000 claims description 12
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 11
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 claims description 10
- 239000012046 mixed solvent Substances 0.000 claims description 10
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 9
- -1 aliphatic alcohols Chemical class 0.000 claims description 9
- 239000002994 raw material Substances 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 238000010828 elution Methods 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 235000019270 ammonium chloride Nutrition 0.000 claims description 6
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 6
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 5
- 239000012670 alkaline solution Substances 0.000 claims description 5
- 230000001376 precipitating effect Effects 0.000 claims description 4
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 3
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 3
- 238000010979 pH adjustment Methods 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 238000013048 microbiological method Methods 0.000 claims description 2
- 238000000935 solvent evaporation Methods 0.000 claims description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims 2
- 238000001816 cooling Methods 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- 229960000958 deferoxamine Drugs 0.000 abstract description 15
- 238000000746 purification Methods 0.000 abstract description 12
- 244000005700 microbiome Species 0.000 abstract description 3
- 238000002955 isolation Methods 0.000 abstract description 2
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 239000012535 impurity Substances 0.000 description 18
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 15
- 229920001429 chelating resin Polymers 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 14
- 239000013078 crystal Substances 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical class [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 238000001914 filtration Methods 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 238000000855 fermentation Methods 0.000 description 7
- 230000004151 fermentation Effects 0.000 description 7
- 229910052742 iron Inorganic materials 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000005377 adsorption chromatography Methods 0.000 description 4
- 239000003957 anion exchange resin Substances 0.000 description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 4
- 241001137868 Streptomyces pilosus Species 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 229960001425 deferoxamine mesylate Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- KCRQZLMAZHZDCL-UHFFFAOYSA-N n-[5-[[4-[5-[acetyl(hydroxy)amino]pentylamino]-4-oxobutanoyl]-hydroxyamino]pentyl]-n'-(5-aminopentyl)-n'-hydroxybutanediamide;hydrochloride Chemical compound Cl.CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN KCRQZLMAZHZDCL-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000011877 solvent mixture Substances 0.000 description 3
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- 206010065973 Iron Overload Diseases 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- GPEHQHXBPDGGDP-UHFFFAOYSA-N acetonitrile;propan-2-one Chemical compound CC#N.CC(C)=O GPEHQHXBPDGGDP-UHFFFAOYSA-N 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004061 bleaching Methods 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000003729 cation exchange resin Substances 0.000 description 2
- OEUUFNIKLCFNLN-LLVKDONJSA-N chembl432481 Chemical compound OC(=O)[C@@]1(C)CSC(C=2C(=CC(O)=CC=2)O)=N1 OEUUFNIKLCFNLN-LLVKDONJSA-N 0.000 description 2
- 238000010908 decantation Methods 0.000 description 2
- 238000004042 decolorization Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 2
- 239000000391 magnesium silicate Substances 0.000 description 2
- 229910052919 magnesium silicate Inorganic materials 0.000 description 2
- 235000019792 magnesium silicate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000002906 microbiologic effect Effects 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 1
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 101000795655 Canis lupus familiaris Thymic stromal cotransporter homolog Proteins 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 238000003109 Karl Fischer titration Methods 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 208000002903 Thalassemia Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
- RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical group CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 description 1
- FKCBLVCOSCZFHV-UHFFFAOYSA-N acetonitrile;ethanol Chemical compound CCO.CC#N FKCBLVCOSCZFHV-UHFFFAOYSA-N 0.000 description 1
- AUALQMFGWLZREY-UHFFFAOYSA-N acetonitrile;methanol Chemical compound OC.CC#N AUALQMFGWLZREY-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007705 chemical test Methods 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229910052602 gypsum Inorganic materials 0.000 description 1
- 239000010440 gypsum Substances 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000005395 methacrylic acid group Chemical group 0.000 description 1
- 229940087646 methanolamine Drugs 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- OENLEHTYJXMVBG-UHFFFAOYSA-N pyridine;hydrate Chemical compound [OH-].C1=CC=[NH+]C=C1 OENLEHTYJXMVBG-UHFFFAOYSA-N 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9904454A HU227315B1 (en) | 1999-12-01 | 1999-12-01 | Process having several steps for producing deferoxamine mesilate of high purity |
| HU9904454 | 1999-12-01 | ||
| PCT/US2000/032574 WO2001040164A1 (en) | 1999-12-01 | 2000-11-30 | A multistage process for the preparation of highly pure deferoxamine mesylate salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2003515579A true JP2003515579A (ja) | 2003-05-07 |
Family
ID=90000087
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001541852A Pending JP2003515579A (ja) | 1999-12-01 | 2000-11-30 | 高純度デフェロキサミン・メシレート塩の製造のための多段階プロセス |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP1235791A4 (ko) |
| JP (1) | JP2003515579A (ko) |
| KR (1) | KR20020067044A (ko) |
| CN (1) | CN1433399A (ko) |
| AU (1) | AU1935101A (ko) |
| CA (1) | CA2392925A1 (ko) |
| CZ (1) | CZ20021823A3 (ko) |
| HU (1) | HU227315B1 (ko) |
| MX (1) | MXPA02005377A (ko) |
| PL (1) | PL355328A1 (ko) |
| RU (1) | RU2002114073A (ko) |
| SK (1) | SK7472002A3 (ko) |
| WO (1) | WO2001040164A1 (ko) |
| YU (1) | YU39602A (ko) |
| ZA (1) | ZA200204030B (ko) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111544374A (zh) * | 2020-05-13 | 2020-08-18 | 中国人民解放军总医院第四医学中心 | 注射用甲磺酸去铁胺在治疗增龄性骨丢失及骨髓干细胞衰老中的应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH438351A (de) * | 1959-09-25 | 1967-06-30 | Ciba Geigy | Verfahren zur Herstellung neuer Wuchsstoffe |
| FR1898M (fr) * | 1961-04-07 | 1963-07-08 | Ciba Geigy | Nouvelle substance utilisable en thérapeutique. |
| WO1993003045A1 (en) * | 1991-08-09 | 1993-02-18 | The Regents Of The University Of California | Process for purer organic metal ion chelate complexes |
| US5254724A (en) * | 1991-10-30 | 1993-10-19 | University Of Florida Research Foundation, Inc. | Method for synthesis of desferrioxamine B, analogs and homologs thereof |
| HU214452B (hu) * | 1992-06-01 | 1998-03-30 | BIOGAL Gyógyszergyár Rt. | Eljárás nagytisztaságú deferoxamin-B-sók előállítására |
-
1999
- 1999-12-01 HU HU9904454A patent/HU227315B1/hu not_active IP Right Cessation
-
2000
- 2000-11-30 EP EP00982299A patent/EP1235791A4/en not_active Withdrawn
- 2000-11-30 AU AU19351/01A patent/AU1935101A/en not_active Abandoned
- 2000-11-30 JP JP2001541852A patent/JP2003515579A/ja active Pending
- 2000-11-30 CZ CZ20021823A patent/CZ20021823A3/cs unknown
- 2000-11-30 WO PCT/US2000/032574 patent/WO2001040164A1/en not_active Application Discontinuation
- 2000-11-30 YU YU39602A patent/YU39602A/sh unknown
- 2000-11-30 SK SK747-2002A patent/SK7472002A3/sk not_active Application Discontinuation
- 2000-11-30 PL PL00355328A patent/PL355328A1/xx unknown
- 2000-11-30 CN CN00818750A patent/CN1433399A/zh active Pending
- 2000-11-30 RU RU2002114073/04A patent/RU2002114073A/ru unknown
- 2000-11-30 MX MXPA02005377A patent/MXPA02005377A/es unknown
- 2000-11-30 KR KR1020027007014A patent/KR20020067044A/ko not_active Application Discontinuation
- 2000-11-30 CA CA002392925A patent/CA2392925A1/en not_active Abandoned
-
2002
- 2002-05-21 ZA ZA200204030A patent/ZA200204030B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SK7472002A3 (en) | 2003-03-04 |
| WO2001040164A1 (en) | 2001-06-07 |
| EP1235791A4 (en) | 2006-03-08 |
| CN1433399A (zh) | 2003-07-30 |
| KR20020067044A (ko) | 2002-08-21 |
| AU1935101A (en) | 2001-06-12 |
| PL355328A1 (en) | 2004-04-19 |
| MXPA02005377A (es) | 2002-12-05 |
| HUP9904454A2 (hu) | 2001-08-28 |
| YU39602A (sh) | 2005-07-19 |
| HU9904454D0 (en) | 2000-02-28 |
| RU2002114073A (ru) | 2004-01-20 |
| HU227315B1 (en) | 2011-03-28 |
| CZ20021823A3 (cs) | 2003-02-12 |
| EP1235791A1 (en) | 2002-09-04 |
| CA2392925A1 (en) | 2001-06-07 |
| ZA200204030B (en) | 2003-05-21 |
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