KR20060052874A - 마크로라이드의 정제 방법 - Google Patents
마크로라이드의 정제 방법 Download PDFInfo
- Publication number
- KR20060052874A KR20060052874A KR1020067001618A KR20067001618A KR20060052874A KR 20060052874 A KR20060052874 A KR 20060052874A KR 1020067001618 A KR1020067001618 A KR 1020067001618A KR 20067001618 A KR20067001618 A KR 20067001618A KR 20060052874 A KR20060052874 A KR 20060052874A
- Authority
- KR
- South Korea
- Prior art keywords
- eluent
- volume
- macrolide
- water
- loading
- 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
- 238000000034 method Methods 0.000 title claims abstract description 93
- 239000003120 macrolide antibiotic agent Substances 0.000 title claims abstract description 67
- 238000000746 purification Methods 0.000 title description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 190
- 229920005989 resin Polymers 0.000 claims abstract description 131
- 239000011347 resin Substances 0.000 claims abstract description 131
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 95
- 238000011068 loading method Methods 0.000 claims abstract description 88
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 82
- 239000003480 eluent Substances 0.000 claims abstract description 77
- 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 claims abstract description 54
- 239000003463 adsorbent Substances 0.000 claims abstract description 53
- 229960001967 tacrolimus Drugs 0.000 claims abstract description 53
- 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 claims abstract description 53
- 229940041033 macrolides Drugs 0.000 claims abstract description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 165
- 239000012535 impurity Substances 0.000 claims description 50
- 239000000203 mixture Substances 0.000 claims description 45
- 230000002829 reductive effect Effects 0.000 claims description 41
- 230000000274 adsorptive effect Effects 0.000 claims description 39
- 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 37
- 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 36
- 238000001179 sorption measurement Methods 0.000 claims description 29
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 25
- 229920001429 chelating resin Polymers 0.000 claims description 25
- 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 25
- 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 24
- 229960002930 sirolimus Drugs 0.000 claims description 24
- 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 22
- 229960005167 everolimus Drugs 0.000 claims description 22
- 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 22
- 229960005330 pimecrolimus Drugs 0.000 claims description 22
- 239000012296 anti-solvent Substances 0.000 claims description 18
- 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 claims description 15
- 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 claims description 15
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 13
- 239000003960 organic solvent Substances 0.000 claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 150000007522 mineralic acids Chemical class 0.000 claims description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- 150000001924 cycloalkanes Chemical class 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 229960004592 isopropanol Drugs 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 238000010828 elution Methods 0.000 description 37
- 238000004587 chromatography analysis Methods 0.000 description 18
- 238000003756 stirring Methods 0.000 description 15
- 239000013078 crystal Substances 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 238000000926 separation method Methods 0.000 description 11
- 239000012141 concentrate Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 8
- 238000007792 addition Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000011149 active material Substances 0.000 description 5
- 239000002024 ethyl acetate extract Substances 0.000 description 5
- 238000011049 filling Methods 0.000 description 5
- 238000004891 communication Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 238000002360 preparation method Methods 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
- 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
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 125000003118 aryl group Chemical group 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
- 238000002474 experimental method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 230000001861 immunosuppressant effect Effects 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 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
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-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
- 101100313763 Arabidopsis thaliana TIM22-2 gene Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229930105110 Cyclosporin A Natural products 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
- GPEHQHXBPDGGDP-UHFFFAOYSA-N acetonitrile;propan-2-one Chemical compound CC#N.CC(C)=O GPEHQHXBPDGGDP-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
- 238000004458 analytical method Methods 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
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000013626 chemical specie Substances 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
- 238000011109 contamination 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
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 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
- 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
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000000686 lactone group Chemical group 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Genetics & Genomics (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49007003P | 2003-07-24 | 2003-07-24 | |
| US60/490,070 | 2003-07-24 | ||
| US53936304P | 2004-01-26 | 2004-01-26 | |
| US60/539,363 | 2004-01-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20060052874A true KR20060052874A (ko) | 2006-05-19 |
Family
ID=34107827
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020067001618A Abandoned KR20060052874A (ko) | 2003-07-24 | 2004-07-26 | 마크로라이드의 정제 방법 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US7220357B2 (https=) |
| EP (1) | EP1558622B1 (https=) |
| JP (1) | JP2007521013A (https=) |
| KR (1) | KR20060052874A (https=) |
| AT (1) | ATE378345T1 (https=) |
| CA (1) | CA2533548C (https=) |
| DE (1) | DE602004010059T2 (https=) |
| DK (1) | DK1558622T3 (https=) |
| ES (1) | ES2297481T3 (https=) |
| PL (1) | PL1558622T3 (https=) |
| PT (1) | PT1558622E (https=) |
| TW (1) | TW200523266A (https=) |
| WO (1) | WO2005010015A1 (https=) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7645876B2 (en) * | 2004-12-01 | 2010-01-12 | TEVA Gyógyszergyár Zártkörúen Müködö Részvénytársaság | Processes for producing crystalline macrolides |
| RU2317991C1 (ru) * | 2003-12-05 | 2008-02-27 | Байокон Лимитид | Способ выделения и очистки макролидов |
| WO2006069333A1 (en) * | 2004-12-22 | 2006-06-29 | Teva Gyógyszergyár Zàrtköruen Muködo Rèszvènytàrsasàg | Method of purifying macrolides |
| BRPI0619592A2 (pt) * | 2005-12-07 | 2016-09-06 | Wyeth Corp | métodos para medir a qualidade da partícula de um composto de rapamicina, para determinar o tamanho de partícula médio de uma amostra e a cristalinidade de um composto de rapamicina, e para a purificação de rapamicina |
| KR100859670B1 (ko) * | 2006-09-13 | 2008-09-23 | 동국제약 주식회사 | 타크로리무스를 고수율 및 고순도로 정제하는 방법 |
| CA2668134A1 (en) * | 2006-11-06 | 2008-05-15 | Teva Gyogyszergyar Zartkoerueen Muekoedoe Reszvenytarsasag | Ascomycin and pimecrolimus having reduced levels of des-methylascomycin and 32-deoxy-32-epichloro-desmethylascomycin respectively, and methods for preparation thereof |
| KR100891313B1 (ko) * | 2007-08-17 | 2009-03-31 | (주) 제노텍 | 담체로 작용하는 흡착성 수지의 제공에 의한 트리사이클로화합물의 생산 및 추출 방법 |
| PL2792254T3 (pl) * | 2009-04-16 | 2017-06-30 | Ocean Spray Cranberries, Inc. | Ekstrakcja związków fenolowych i ich zastosowanie w kompozycjach z kwasem fumarowym |
| CN106478664B (zh) * | 2016-08-29 | 2017-12-05 | 广东蓝宝制药有限公司 | 一种发酵液中提取纯化他克莫司的方法 |
| PL3619215T3 (pl) | 2017-05-01 | 2022-03-21 | Meda Pharma Gmbh & Co. Kg | Sposób przekształcania surowej askomycyny w oczyszczony pimecrolimus |
| CN108409751A (zh) * | 2018-02-24 | 2018-08-17 | 海正药业(杭州)有限公司 | 一种子囊霉素的纯化方法 |
| CN111693635A (zh) * | 2020-07-23 | 2020-09-22 | 北京和合医学诊断技术股份有限公司 | 检测血液中雷帕霉素含量的方法 |
| CN113325108B (zh) * | 2021-06-04 | 2022-12-09 | 山东霆科药业有限公司 | 一种他克莫司软膏的样品前处理方法 |
| CN115716839A (zh) * | 2022-11-15 | 2023-02-28 | 无锡福祈制药有限公司 | 一种依维莫司杂质的合成方法 |
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| DE2121517C3 (de) | 1971-04-30 | 1974-06-27 | Leningradskij Nautschno-Issledowatelskij Institut Antibiotikow, Ssr, Leningrad (Sowjetunion) | Verfahren zur Gewinnung von Amphoterizin B |
| 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 |
| JP2639737B2 (ja) | 1990-01-23 | 1997-08-13 | 寳酒造株式会社 | 新規ｒ１０６類化合物 |
| US5116756A (en) | 1991-01-28 | 1992-05-26 | Merck & Co., Inc. | Process for producing FK-506 |
| JPH06501026A (ja) | 1991-04-11 | 1994-01-27 | ファイザー・インコーポレーテッド | ストレプトミセス・ブレジェンシス由来の新規の免疫抑制剤 |
| US5091389A (en) | 1991-04-23 | 1992-02-25 | Merck & Co., Inc. | Lipophilic macrolide useful as an immunosuppressant |
| WO1993018042A1 (en) | 1992-03-02 | 1993-09-16 | Pfizer Inc. | Desosamino derivatives of macrolides as immunosuppressants and antifungal agents |
| 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 |
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| TW553946B (en) * | 1999-09-08 | 2003-09-21 | Fujisawa Pharmaceutical Co | Method for separating lactone-containing high-molecular weight compounds |
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| FR2803307A1 (fr) * | 1999-12-30 | 2001-07-06 | Centre Nat Rech Scient | Lignees de lymphocytes t cd4 specifiques de type th1 et procede pour leur induction ex vivo |
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| AUPQ801700A0 (en) * | 2000-06-07 | 2000-06-29 | Peplin Research Pty Ltd | Enzyme and viral activation |
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-
2004
- 2004-07-26 TW TW093122295A patent/TW200523266A/zh unknown
- 2004-07-26 AT AT04779384T patent/ATE378345T1/de active
- 2004-07-26 DE DE602004010059T patent/DE602004010059T2/de not_active Expired - Lifetime
- 2004-07-26 PL PL04779384T patent/PL1558622T3/pl unknown
- 2004-07-26 DK DK04779384T patent/DK1558622T3/da active
- 2004-07-26 JP JP2006521315A patent/JP2007521013A/ja not_active Ceased
- 2004-07-26 PT PT04779384T patent/PT1558622E/pt unknown
- 2004-07-26 CA CA2533548A patent/CA2533548C/en not_active Expired - Fee Related
- 2004-07-26 ES ES04779384T patent/ES2297481T3/es not_active Expired - Lifetime
- 2004-07-26 WO PCT/US2004/024318 patent/WO2005010015A1/en not_active Ceased
- 2004-07-26 EP EP04779384A patent/EP1558622B1/en not_active Expired - Lifetime
- 2004-07-26 KR KR1020067001618A patent/KR20060052874A/ko not_active Abandoned
- 2004-07-26 US US10/899,757 patent/US7220357B2/en not_active Expired - Fee Related
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2007
- 2007-01-17 US US11/654,758 patent/US20070117976A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| PT1558622E (pt) | 2007-12-04 |
| WO2005010015B1 (en) | 2005-03-17 |
| US7220357B2 (en) | 2007-05-22 |
| DE602004010059D1 (de) | 2007-12-27 |
| PL1558622T3 (pl) | 2008-06-30 |
| DK1558622T3 (da) | 2008-02-25 |
| DE602004010059T2 (de) | 2008-09-11 |
| CA2533548C (en) | 2010-02-16 |
| ES2297481T3 (es) | 2008-05-01 |
| TW200523266A (en) | 2005-07-16 |
| JP2007521013A (ja) | 2007-08-02 |
| EP1558622B1 (en) | 2007-11-14 |
| US20050027112A1 (en) | 2005-02-03 |
| EP1558622A1 (en) | 2005-08-03 |
| US20070117976A1 (en) | 2007-05-24 |
| CA2533548A1 (en) | 2005-02-03 |
| WO2005010015A1 (en) | 2005-02-03 |
| ATE378345T1 (de) | 2007-11-15 |
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