CA2586692A1 - Method of purifying macrolides - Google Patents
Method of purifying macrolides Download PDFInfo
- Publication number
- CA2586692A1 CA2586692A1 CA002586692A CA2586692A CA2586692A1 CA 2586692 A1 CA2586692 A1 CA 2586692A1 CA 002586692 A CA002586692 A CA 002586692A CA 2586692 A CA2586692 A CA 2586692A CA 2586692 A1 CA2586692 A1 CA 2586692A1
- Authority
- CA
- Canada
- Prior art keywords
- macrolide
- bed
- thf
- eluent
- 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.)
- Abandoned
Links
- 239000003120 macrolide antibiotic agent Substances 0.000 title claims abstract description 69
- 238000000034 method Methods 0.000 title claims abstract description 45
- 229940041033 macrolides Drugs 0.000 title description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 106
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 103
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 60
- 238000001179 sorption measurement Methods 0.000 claims abstract description 57
- 229920005989 resin Polymers 0.000 claims abstract description 53
- 239000011347 resin Substances 0.000 claims abstract description 53
- 238000011068 loading method Methods 0.000 claims abstract description 39
- 239000003480 eluent Substances 0.000 claims abstract description 38
- 239000003960 organic solvent Substances 0.000 claims abstract description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 19
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims abstract description 14
- 235000019441 ethanol Nutrition 0.000 claims abstract description 8
- 229960004592 isopropanol Drugs 0.000 claims abstract description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
- 239000002904 solvent Substances 0.000 claims description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- ZDQSOHOQTUFQEM-XCXYXIJFSA-N ascomycin Natural products CC[C@H]1C=C(C)C[C@@H](C)C[C@@H](OC)[C@H]2O[C@@](O)([C@@H](C)C[C@H]2OC)C(=O)C(=O)N3CCCC[C@@H]3C(=O)O[C@H]([C@H](C)[C@@H](O)CC1=O)C(=C[C@@H]4CC[C@@H](O)[C@H](C4)OC)C ZDQSOHOQTUFQEM-XCXYXIJFSA-N 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- ZDQSOHOQTUFQEM-PKUCKEGBSA-N ascomycin Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C\C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 ZDQSOHOQTUFQEM-PKUCKEGBSA-N 0.000 claims description 14
- 238000000926 separation method Methods 0.000 claims description 13
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 11
- 229960002930 sirolimus Drugs 0.000 claims description 11
- KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 claims description 9
- 229960005330 pimecrolimus Drugs 0.000 claims description 9
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- 238000009835 boiling Methods 0.000 claims description 8
- -1 ethyl acetate) Chemical compound 0.000 claims description 8
- 229960005167 everolimus Drugs 0.000 claims description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 229920001429 chelating resin Polymers 0.000 claims description 5
- 238000004891 communication Methods 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000000047 product Substances 0.000 description 55
- 239000007787 solid Substances 0.000 description 32
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 30
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 29
- 229960001967 tacrolimus Drugs 0.000 description 29
- 239000012535 impurity Substances 0.000 description 20
- 238000010828 elution Methods 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 239000012296 anti-solvent Substances 0.000 description 5
- 229940093499 ethyl acetate Drugs 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 4
- RQYGKZGKXDOUEO-HHRHWXIDSA-N dihydro-fk 506 Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)OC([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CCC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 RQYGKZGKXDOUEO-HHRHWXIDSA-N 0.000 description 4
- RQYGKZGKXDOUEO-UHFFFAOYSA-N dihydrotacrolimus Natural products CC1C(O)CC(=O)C(CCC)C=C(C)CC(C)CC(OC)C(C(CC2C)OC)OC2(O)C(=O)C(=O)N2CCCCC2C(=O)OC1C(C)=CC1CCC(O)C(OC)C1 RQYGKZGKXDOUEO-UHFFFAOYSA-N 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 238000007792 addition Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229960003444 immunosuppressant agent Drugs 0.000 description 3
- 230000001861 immunosuppressant effect Effects 0.000 description 3
- 230000003134 recirculating effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 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 2
- 229930105110 Cyclosporin A Natural products 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 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 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000013626 chemical specie Substances 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- FJQXCDYVZAHXNS-UHFFFAOYSA-N methadone hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 FJQXCDYVZAHXNS-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000274 adsorptive effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[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 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin 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)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 150000008266 deoxy sugars Chemical class 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229960003276 erythromycin Drugs 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
- 239000012467 final product Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000000686 lactone group Chemical group 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/282—Porous sorbents
- B01J20/285—Porous sorbents based on polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/42—Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
- B01D15/424—Elution mode
- B01D15/426—Specific type of solvent
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D267/22—Eight-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/18—Eight-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Saccharide Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63862804P | 2004-12-22 | 2004-12-22 | |
| US60/638,628 | 2004-12-22 | ||
| US63881504P | 2004-12-23 | 2004-12-23 | |
| US60/638,815 | 2004-12-23 | ||
| PCT/US2005/046856 WO2006069333A1 (en) | 2004-12-22 | 2005-12-22 | Method of purifying macrolides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2586692A1 true CA2586692A1 (en) | 2006-06-29 |
Family
ID=36128612
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002586692A Abandoned CA2586692A1 (en) | 2004-12-22 | 2005-12-22 | Method of purifying macrolides |
| CA002586700A Abandoned CA2586700A1 (en) | 2004-12-22 | 2005-12-22 | Method of purifying tacrolimus |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002586700A Abandoned CA2586700A1 (en) | 2004-12-22 | 2005-12-22 | Method of purifying tacrolimus |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US20060142565A1 (https=) |
| EP (2) | EP1828205A1 (https=) |
| JP (2) | JP2007523201A (https=) |
| CA (2) | CA2586692A1 (https=) |
| IL (2) | IL183241A0 (https=) |
| MX (2) | MX2007005868A (https=) |
| TW (2) | TW200637834A (https=) |
| WO (2) | WO2006069333A1 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008059516A2 (en) * | 2006-08-21 | 2008-05-22 | Concord Biotech Limited | Process for purification of macrolides |
| EP2090580B1 (en) | 2006-11-27 | 2014-06-04 | Terumo Kabushiki Kaisha | Process for producing o-alkylated rapamycin derivative, and o-alkylated rapamycin derivative |
| KR101003042B1 (ko) * | 2008-03-17 | 2010-12-21 | 종근당바이오 주식회사 | 고순도 타크로리무스의 정제 방법 |
| GB201020032D0 (en) * | 2010-11-25 | 2011-01-12 | Sigmoid Pharma Ltd | Composition |
| KR101344012B1 (ko) | 2012-04-09 | 2013-12-23 | 인하대학교 산학협력단 | 모사이동층 크로마토그래피를 이용하여 타크로리무스와 아스코마이신의 혼합액으로부터 타크로리무스를 분리하는 방법 |
| CN103554133B (zh) * | 2013-10-31 | 2015-06-24 | 国药集团川抗制药有限公司 | 一种制备高纯度他克莫司的工艺 |
| CN105301159B (zh) * | 2015-10-29 | 2017-01-18 | 无锡福祈制药有限公司 | 一种西罗莫司的高效液相色谱分析方法 |
| CN117402175A (zh) * | 2023-10-18 | 2024-01-16 | 国药集团川抗制药有限公司 | 一种他克莫司的结晶方法及其应用 |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3244592A (en) * | 1962-06-09 | 1966-04-05 | Arai Tadashi | Ascomycin and process for its production |
| US3993749A (en) * | 1974-04-12 | 1976-11-23 | Ayerst Mckenna And Harrison Ltd. | Rapamycin and process of preparation |
| US4160861A (en) * | 1977-10-03 | 1979-07-10 | Merck & Co., Inc. | Method for the separation of antibiotic macrolides |
| US4894366A (en) * | 1984-12-03 | 1990-01-16 | Fujisawa Pharmaceutical Company, Ltd. | Tricyclo compounds, a process for their production and a pharmaceutical composition containing the same |
| US5182207A (en) * | 1984-09-14 | 1993-01-26 | American Cyanamid Company | Strains of streptomyces thermoarchaensis |
| US4874843A (en) * | 1987-12-03 | 1989-10-17 | Eli Lilly And Company | Chromatographic purification process |
| JP2639737B2 (ja) * | 1990-01-23 | 1997-08-13 | 寳酒造株式会社 | 新規ｒ１０６類化合物 |
| US5194378A (en) * | 1991-01-28 | 1993-03-16 | Merck & Co., Inc. | Process for producing fk-506 |
| US5116756A (en) * | 1991-01-28 | 1992-05-26 | Merck & Co., Inc. | Process for producing FK-506 |
| US5091389A (en) * | 1991-04-23 | 1992-02-25 | Merck & Co., Inc. | Lipophilic macrolide useful as an immunosuppressant |
| US5227295A (en) * | 1991-11-08 | 1993-07-13 | Dowelanco | Process for isolating A83543 and its components |
| WO1993018049A1 (en) * | 1992-03-02 | 1993-09-16 | Pfizer Inc. | Fluorosugar derivatives of macrolides |
| WO1993018042A1 (en) * | 1992-03-02 | 1993-09-16 | Pfizer Inc. | Desosamino derivatives of macrolides as immunosuppressants and antifungal agents |
| US5264355A (en) * | 1992-07-02 | 1993-11-23 | Merck & Co., Inc. | Methlating enzyme from streptomyces MA6858 |
| UA41884C2 (uk) * | 1993-11-05 | 2001-10-15 | Амерікан Хоум Продактс Корпорейшн | Спосіб відокремлення рапаміцину від кислотних, основних та неполярних нейтральних домішок, присутніх в концентраті екстрактів ферментаційного бульйону або маточних розчинів |
| US5622866A (en) * | 1994-06-23 | 1997-04-22 | Merck & Co., Inc. | Expression cassettes useful in construction of integrative and replicative expression vectors for Streptomyces |
| GB9618952D0 (en) * | 1996-09-11 | 1996-10-23 | Sandoz Ltd | Process |
| US5616595A (en) * | 1995-06-07 | 1997-04-01 | Abbott Laboratories | Process for recovering water insoluble compounds from a fermentation broth |
| MXPA01003376A (es) * | 1998-10-02 | 2002-11-07 | Kosan Biosciences Inc | Enzimas policetido sintetasa y construcciones de acido desoxirribonucleico recombinante para las mismas. |
| AU1214400A (en) * | 1998-10-20 | 2000-05-08 | Ben Venue Laboratories, Inc. | Process for purification of solvents useful in the preparation of pharmaceuticalcompositions |
| DE69903465T2 (de) * | 1998-11-09 | 2003-06-26 | Aventis Pharma Deutschland Gmbh | Vancoresmycin, verfahren zu dessen herstellung und dessen anwendung als arzneimittel |
| JP3750527B2 (ja) * | 1999-05-25 | 2006-03-01 | アステラス製薬株式会社 | 類似有機化合物を分離する方法 |
| TW553946B (en) * | 1999-09-08 | 2003-09-21 | Fujisawa Pharmaceutical Co | Method for separating lactone-containing high-molecular weight compounds |
| HRP20020683A2 (en) * | 2000-02-24 | 2004-12-31 | Biogal Gyogyszergyar | Method of purifying a fermentation broth |
| MXPA04007847A (es) * | 2002-02-13 | 2005-02-24 | Biogal Gyogyszergyar | Metodo para extraer un macrolido de biomateria. |
| PL1558622T3 (pl) * | 2003-07-24 | 2008-06-30 | Teva Gyogyszergyar Zartkoerueen Muekoedoe Reszvenytarsasag | Sposób oczyszczania makrolidów |
-
2005
- 2005-12-22 CA CA002586692A patent/CA2586692A1/en not_active Abandoned
- 2005-12-22 US US11/317,155 patent/US20060142565A1/en not_active Abandoned
- 2005-12-22 WO PCT/US2005/046856 patent/WO2006069333A1/en not_active Ceased
- 2005-12-22 US US11/317,152 patent/US20060149057A1/en not_active Abandoned
- 2005-12-22 MX MX2007005868A patent/MX2007005868A/es not_active Application Discontinuation
- 2005-12-22 JP JP2006554356A patent/JP2007523201A/ja active Pending
- 2005-12-22 WO PCT/US2005/047264 patent/WO2006069386A1/en not_active Ceased
- 2005-12-22 JP JP2006554355A patent/JP2007523200A/ja active Pending
- 2005-12-22 EP EP05855772A patent/EP1828205A1/en not_active Withdrawn
- 2005-12-22 TW TW094145958A patent/TW200637834A/zh unknown
- 2005-12-22 TW TW094145959A patent/TW200637835A/zh unknown
- 2005-12-22 CA CA002586700A patent/CA2586700A1/en not_active Abandoned
- 2005-12-22 MX MX2007005867A patent/MX2007005867A/es unknown
- 2005-12-22 EP EP05855421A patent/EP1828204A1/en not_active Withdrawn
-
2007
- 2007-05-15 IL IL183241A patent/IL183241A0/en unknown
- 2007-05-15 IL IL183240A patent/IL183240A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006069333A1 (en) | 2006-06-29 |
| WO2006069386A1 (en) | 2006-06-29 |
| IL183240A0 (en) | 2007-08-19 |
| IL183241A0 (en) | 2007-08-19 |
| TW200637835A (en) | 2006-11-01 |
| JP2007523201A (ja) | 2007-08-16 |
| JP2007523200A (ja) | 2007-08-16 |
| MX2007005867A (es) | 2007-07-04 |
| CA2586700A1 (en) | 2006-06-29 |
| US20060142565A1 (en) | 2006-06-29 |
| EP1828204A1 (en) | 2007-09-05 |
| US20060149057A1 (en) | 2006-07-06 |
| TW200637834A (en) | 2006-11-01 |
| MX2007005868A (es) | 2007-07-04 |
| EP1828205A1 (en) | 2007-09-05 |
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