JP2005527484A5 - - Google Patents
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- Publication number
- JP2005527484A5 JP2005527484A5 JP2003546834A JP2003546834A JP2005527484A5 JP 2005527484 A5 JP2005527484 A5 JP 2005527484A5 JP 2003546834 A JP2003546834 A JP 2003546834A JP 2003546834 A JP2003546834 A JP 2003546834A JP 2005527484 A5 JP2005527484 A5 JP 2005527484A5
- Authority
- JP
- Japan
- Prior art keywords
- levofloxacin
- solvent
- process according
- acetonitrile
- purity
- 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
- GSDSWSVVBLHKDQ-JTQLQIEISA-N (2S)-7-fluoro-2-methyl-6-(4-methylpiperazin-1-yl)-10-oxo-4-oxa-1-azatricyclo[7.3.1.0^{5,13}]trideca-5(13),6,8,11-tetraene-11-carboxylic acid Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims description 41
- 229960003376 levofloxacin Drugs 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- 230000003078 antioxidant Effects 0.000 claims description 12
- 239000003963 antioxidant agent Substances 0.000 claims description 12
- 235000006708 antioxidants Nutrition 0.000 claims description 12
- 238000002425 crystallisation Methods 0.000 claims description 8
- 230000005712 crystallization Effects 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 238000000746 purification Methods 0.000 claims description 7
- 229960005070 ascorbic acid Drugs 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 235000010323 ascorbic acid Nutrition 0.000 claims description 4
- 239000011668 ascorbic acid Substances 0.000 claims description 4
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 4
- HRZFUMHJMZEROT-UHFFFAOYSA-L 7681-57-4 Chemical group [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 3
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 3
- 230000001809 detectable Effects 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 28
- LRHPLDYGYMQRHN-UHFFFAOYSA-N n-butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims 18
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims 16
- 239000002904 solvent Substances 0.000 claims 16
- 239000012046 mixed solvent Substances 0.000 claims 12
- SUIQUYDRLGGZOL-RCWTXCDDSA-N Levofloxacin Hemihydrate Chemical compound O.C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1.C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 SUIQUYDRLGGZOL-RCWTXCDDSA-N 0.000 claims 10
- 239000002798 polar solvent Substances 0.000 claims 6
- TYQCGQRIZGCHNB-JLAZNSOCSA-N L-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 claims 4
- 238000007792 addition Methods 0.000 claims 3
- SRUQARLMFOLRDN-UHFFFAOYSA-N 1-(2,4,5-Trihydroxyphenyl)-1-butanone Chemical compound CCCC(=O)C1=CC(O)=C(O)C=C1O SRUQARLMFOLRDN-UHFFFAOYSA-N 0.000 claims 1
- SKDGWNHUETZZCS-UHFFFAOYSA-N 2,3-ditert-butylphenol Chemical compound CC(C)(C)C1=CC=CC(O)=C1C(C)(C)C SKDGWNHUETZZCS-UHFFFAOYSA-N 0.000 claims 1
- 229940043253 Butylated Hydroxyanisole Drugs 0.000 claims 1
- 229940095259 Butylated Hydroxytoluene Drugs 0.000 claims 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 claims 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N Butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims 1
- 229940047036 Calcium ascorbate Drugs 0.000 claims 1
- WKRSSAPQZDHYRV-VIFPVBQESA-N Desmethyl levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCNCC1 WKRSSAPQZDHYRV-VIFPVBQESA-N 0.000 claims 1
- GHKOFFNLGXMVNJ-UHFFFAOYSA-N Dilauryl thiodipropionate Chemical compound CCCCCCCCCCCCOC(=O)CCSCCC(=O)OCCCCCCCCCCCC GHKOFFNLGXMVNJ-UHFFFAOYSA-N 0.000 claims 1
- 239000003508 Dilauryl thiodipropionate Substances 0.000 claims 1
- 229940091561 Guaiac Drugs 0.000 claims 1
- 241000147041 Guaiacum officinale Species 0.000 claims 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims 1
- 229940075579 Propyl Gallate Drugs 0.000 claims 1
- 229960005055 SODIUM ASCORBATE Drugs 0.000 claims 1
- BGNXCDMCOKJUMV-UHFFFAOYSA-N TBHQ Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims 1
- 239000003490 Thiodipropionic acid Substances 0.000 claims 1
- ODJQKYXPKWQWNK-UHFFFAOYSA-N Thiodipropionic acid Chemical compound OC(=O)CCSCCC(O)=O ODJQKYXPKWQWNK-UHFFFAOYSA-N 0.000 claims 1
- 229960001295 Tocopherol Drugs 0.000 claims 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 claims 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims 1
- 235000010376 calcium ascorbate Nutrition 0.000 claims 1
- 239000011692 calcium ascorbate Substances 0.000 claims 1
- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 claims 1
- 235000019304 dilauryl thiodipropionate Nutrition 0.000 claims 1
- 238000004090 dissolution Methods 0.000 claims 1
- 235000010350 erythorbic acid Nutrition 0.000 claims 1
- 239000004318 erythorbic acid Substances 0.000 claims 1
- 229920000591 gum Polymers 0.000 claims 1
- 229940026239 isoascorbic acid Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- ZTHYODDOHIVTJV-UHFFFAOYSA-N propyl 3,4,5-trihydroxybenzoate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims 1
- 235000010388 propyl gallate Nutrition 0.000 claims 1
- 239000000473 propyl gallate Substances 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 235000010378 sodium ascorbate Nutrition 0.000 claims 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims 1
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims 1
- 235000019303 thiodipropionic acid Nutrition 0.000 claims 1
- 235000010384 tocopherol Nutrition 0.000 claims 1
- 239000011732 tocopherol Substances 0.000 claims 1
- 229930003799 tocopherols Natural products 0.000 claims 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- CFLBIADORGSMCX-UHFFFAOYSA-N 2H-1,4-benzoxazine-6-carboxylic acid Chemical compound O1CC=NC2=CC(C(=O)O)=CC=C21 CFLBIADORGSMCX-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Vitamin C Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1H-quinoline-3-carboxylic acid Chemical class C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 description 1
- PVTXJGJDOHYFOX-UHFFFAOYSA-N 2H-1,4-benzoxazine Chemical class C1=CC=C2N=CCOC2=C1 PVTXJGJDOHYFOX-UHFFFAOYSA-N 0.000 description 1
- -1 4-methyl-1-piperazinyl Chemical group 0.000 description 1
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N Levofloxacin Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 1
- NVKWWNNJFKZNJO-YFKPBYRVSA-N Levofloxacin carboxylic acid Chemical compound N1([C@@H](C)CO2)C=C(C(O)=O)C(=O)C3=C1C2=C(F)C(F)=C3 NVKWWNNJFKZNJO-YFKPBYRVSA-N 0.000 description 1
- 229960001699 Ofloxacin Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical group CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33431601P | 2001-11-29 | 2001-11-29 | |
| US35493902P | 2002-02-11 | 2002-02-11 | |
| US26296502A | 2002-10-03 | 2002-10-03 | |
| US10/263,192 US7629458B2 (en) | 2001-10-03 | 2002-10-03 | Preparation of levofloxacin and hemihydrate thereof |
| PCT/US2002/038182 WO2003045329A2 (en) | 2001-11-29 | 2002-11-27 | Methods for the purification of levofloxacin |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006127862A Division JP2006219496A (ja) | 2001-11-29 | 2006-05-01 | レボフロキサシンの精製製法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005527484A JP2005527484A (ja) | 2005-09-15 |
| JP2005527484A5 true JP2005527484A5 (pt) | 2006-06-22 |
Family
ID=31892240
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003546834A Pending JP2005527484A (ja) | 2001-11-29 | 2002-11-27 | レボフロキサシンの精製製法 |
| JP2006127862A Withdrawn JP2006219496A (ja) | 2001-11-29 | 2006-05-01 | レボフロキサシンの精製製法 |
| JP2007216178A Pending JP2008007517A (ja) | 2001-11-29 | 2007-08-22 | レボフロキサシンの精製製法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006127862A Withdrawn JP2006219496A (ja) | 2001-11-29 | 2006-05-01 | レボフロキサシンの精製製法 |
| JP2007216178A Pending JP2008007517A (ja) | 2001-11-29 | 2007-08-22 | レボフロキサシンの精製製法 |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1460997A4 (pt) |
| JP (3) | JP2005527484A (pt) |
| CN (1) | CN1596256A (pt) |
| AU (1) | AU2002365416A1 (pt) |
| CA (1) | CA2466860A1 (pt) |
| HR (1) | HRP20040546A2 (pt) |
| HU (1) | HUP0500285A3 (pt) |
| IL (1) | IL162172A0 (pt) |
| IS (1) | IS7288A (pt) |
| MX (1) | MXPA04005196A (pt) |
| NO (1) | NO20042731L (pt) |
| PL (1) | PL374558A1 (pt) |
| WO (1) | WO2003045329A2 (pt) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7629458B2 (en) | 2001-10-03 | 2009-12-08 | Teva Pharmaceutical Industries Ltd. | Preparation of levofloxacin and hemihydrate thereof |
| CN1735620A (zh) * | 2002-12-16 | 2006-02-15 | 兰贝克赛实验室有限公司 | 纯的左氧氟沙星半水合物和它的制备方法 |
| KR100704641B1 (ko) * | 2004-07-21 | 2007-04-06 | 주식회사유한양행 | 고순도의 레보플록사신 제조방법 |
| JP2006273718A (ja) * | 2005-03-28 | 2006-10-12 | Shiono Chemical Co Ltd | レボフロキサシン・１／２水和物の製法 |
| CN1321121C (zh) * | 2005-04-21 | 2007-06-13 | 浙江医药股份有限公司新昌制药厂 | 左氧氟沙星制备及后处理方法 |
| US7964723B2 (en) | 2008-08-02 | 2011-06-21 | Apeloa-Kangyu | And practical process for exclusively producing (S)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido-[1,2,3,de][1,4]benzoxazine-6-carboxylic acid hemihydrate |
| CN102070650B (zh) * | 2011-01-28 | 2012-06-27 | 山东省药品检验所 | 左氧氟沙星-n-氧化物的制备方法 |
| US20120251685A1 (en) * | 2011-04-04 | 2012-10-04 | Martek Biosciences Corporation | Oil-in-Water Emulsions Comprising a Polyunsaturated Fatty Acid and Methods of Making the Same |
| CN105823851A (zh) * | 2015-12-15 | 2016-08-03 | 浙江海洋学院 | 一种检测海水中氧氟沙星对映体的方法 |
| CN108218892A (zh) * | 2018-03-16 | 2018-06-29 | 乐山职业技术学院 | 一种左氧氟沙星的纯化方法 |
| CN114507242B (zh) * | 2022-01-26 | 2023-05-19 | 上虞京新药业有限公司 | 高光学纯度左氧氟沙星的制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK170473B1 (da) * | 1985-06-20 | 1995-09-11 | Daiichi Seiyaku Co | S(-)-pyridobenzoxazinforbindelser |
| US5237060A (en) * | 1985-12-10 | 1993-08-17 | Bayer Aktiengesellschaft | Process of preparing enantiomerically pure 1,8-bridged 4-quinolone-3-carboxylic acids |
| TW208013B (pt) * | 1990-03-01 | 1993-06-21 | Daiichi Co Ltd | |
| CA2125287A1 (en) * | 1992-10-07 | 1994-04-14 | Juan Carlos Carretero Gonzalvez | Process to obtain benzoxazines to be used for the synthesis of ofloxazine, levofloxazine and derivatives |
| KR0125115B1 (ko) * | 1994-03-22 | 1997-12-05 | 김은영 | (-)피페라진 벤즈옥사진 유도체의 제조방법 |
| KR100309871B1 (ko) * | 1999-02-24 | 2001-10-29 | 윤종용 | (-)피리도벤즈옥사진 카르복실산 유도체의 제조방법 |
| US7629458B2 (en) * | 2001-10-03 | 2009-12-08 | Teva Pharmaceutical Industries Ltd. | Preparation of levofloxacin and hemihydrate thereof |
-
2002
- 2002-11-27 MX MXPA04005196A patent/MXPA04005196A/es not_active Application Discontinuation
- 2002-11-27 CA CA002466860A patent/CA2466860A1/en not_active Abandoned
- 2002-11-27 AU AU2002365416A patent/AU2002365416A1/en not_active Abandoned
- 2002-11-27 HU HU0500285A patent/HUP0500285A3/hu unknown
- 2002-11-27 JP JP2003546834A patent/JP2005527484A/ja active Pending
- 2002-11-27 WO PCT/US2002/038182 patent/WO2003045329A2/en active Application Filing
- 2002-11-27 IL IL16217202A patent/IL162172A0/xx unknown
- 2002-11-27 CN CNA028236440A patent/CN1596256A/zh active Pending
- 2002-11-27 PL PL02374558A patent/PL374558A1/xx not_active Application Discontinuation
- 2002-11-27 EP EP02791339A patent/EP1460997A4/en not_active Withdrawn
-
2004
- 2004-05-27 IS IS7288A patent/IS7288A/is unknown
- 2004-06-15 HR HR20040546A patent/HRP20040546A2/hr not_active Application Discontinuation
- 2004-06-29 NO NO20042731A patent/NO20042731L/no not_active Application Discontinuation
-
2006
- 2006-05-01 JP JP2006127862A patent/JP2006219496A/ja not_active Withdrawn
-
2007
- 2007-08-22 JP JP2007216178A patent/JP2008007517A/ja active Pending
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