DE60105016T3 - Verfahren zur reinigung eines salzes der clavulansäure - Google Patents
Verfahren zur reinigung eines salzes der clavulansäure Download PDFInfo
- Publication number
- DE60105016T3 DE60105016T3 DE60105016T DE60105016T DE60105016T3 DE 60105016 T3 DE60105016 T3 DE 60105016T3 DE 60105016 T DE60105016 T DE 60105016T DE 60105016 T DE60105016 T DE 60105016T DE 60105016 T3 DE60105016 T3 DE 60105016T3
- Authority
- DE
- Germany
- Prior art keywords
- salt
- clavulanic acid
- amine
- medium
- amine salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000003839 salts Chemical class 0.000 title claims abstract description 96
- 238000000034 method Methods 0.000 title claims abstract description 84
- 239000002253 acid Substances 0.000 title description 15
- 238000004140 cleaning Methods 0.000 title 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims abstract description 122
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims abstract description 114
- 229960003324 clavulanic acid Drugs 0.000 claims abstract description 109
- -1 amine salt Chemical class 0.000 claims abstract description 86
- 239000012535 impurity Substances 0.000 claims abstract description 33
- 238000005406 washing Methods 0.000 claims abstract description 16
- 238000001953 recrystallisation Methods 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- 239000002609 medium Substances 0.000 claims description 32
- ABVRVIZBZKUTMK-JSYANWSFSA-M potassium clavulanate Chemical compound [K+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 ABVRVIZBZKUTMK-JSYANWSFSA-M 0.000 claims description 31
- 239000000243 solution Substances 0.000 claims description 29
- 239000000047 product Substances 0.000 claims description 28
- 229910052751 metal Inorganic materials 0.000 claims description 27
- 239000002184 metal Substances 0.000 claims description 27
- 150000001412 amines Chemical class 0.000 claims description 23
- NDSQGOBLOMHGLG-UHFFFAOYSA-N 2-(2,5-dioxopyrrolidin-1-yl)-3-(4-hydroxyphenyl)propanoic acid Chemical compound O=C1CCC(=O)N1C(C(=O)O)CC1=CC=C(O)C=C1 NDSQGOBLOMHGLG-UHFFFAOYSA-N 0.000 claims description 21
- 239000003960 organic solvent Substances 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 239000008346 aqueous phase Substances 0.000 claims description 15
- 239000012071 phase Substances 0.000 claims description 15
- 239000002243 precursor Substances 0.000 claims description 15
- 238000000605 extraction Methods 0.000 claims description 11
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 10
- 238000002425 crystallisation Methods 0.000 claims description 10
- 230000008025 crystallization Effects 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 238000000855 fermentation Methods 0.000 claims description 6
- 230000004151 fermentation Effects 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 229940090805 clavulanate Drugs 0.000 claims description 5
- 239000012736 aqueous medium Substances 0.000 claims description 4
- 244000005700 microbiome Species 0.000 claims description 3
- 230000001376 precipitating effect Effects 0.000 claims 1
- 239000013587 production medium Substances 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 abstract description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- 229960000583 acetic acid Drugs 0.000 description 10
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 5
- MFIGJRRHGZYPDD-UHFFFAOYSA-N n,n'-di(propan-2-yl)ethane-1,2-diamine Chemical compound CC(C)NCCNC(C)C MFIGJRRHGZYPDD-UHFFFAOYSA-N 0.000 description 5
- ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- GTEXIOINCJRBIO-UHFFFAOYSA-N 2-[2-(dimethylamino)ethoxy]-n,n-dimethylethanamine Chemical compound CN(C)CCOCCN(C)C GTEXIOINCJRBIO-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical class C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000005233 alkylalcohol group Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- JGVZJRHAZOBPMW-UHFFFAOYSA-N 1,3-bis(dimethylamino)propan-2-ol Chemical compound CN(C)CC(O)CN(C)C JGVZJRHAZOBPMW-UHFFFAOYSA-N 0.000 description 2
- UYMQPNRUQXPLCY-UHFFFAOYSA-N 1-(2-piperidin-1-ylethyl)piperidine Chemical compound C1CCCCN1CCN1CCCCC1 UYMQPNRUQXPLCY-UHFFFAOYSA-N 0.000 description 2
- LRKYLKBLUJXTFL-UHFFFAOYSA-N 1-(piperidin-1-ylmethyl)piperidine Chemical compound C1CCCCN1CN1CCCCC1 LRKYLKBLUJXTFL-UHFFFAOYSA-N 0.000 description 2
- QIJIUJYANDSEKG-UHFFFAOYSA-N 2,4,4-trimethylpentan-2-amine Chemical compound CC(C)(C)CC(C)(C)N QIJIUJYANDSEKG-UHFFFAOYSA-N 0.000 description 2
- OBETXYAYXDNJHR-UHFFFAOYSA-N 2-Ethylhexanoic acid Chemical class CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- 241000187433 Streptomyces clavuligerus Species 0.000 description 2
- 229910052784 alkaline earth metal Chemical class 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 150000004985 diamines Chemical group 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- TXXWBTOATXBWDR-UHFFFAOYSA-N n,n,n',n'-tetramethylhexane-1,6-diamine Chemical compound CN(C)CCCCCCN(C)C TXXWBTOATXBWDR-UHFFFAOYSA-N 0.000 description 2
- SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical class NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- OBETXYAYXDNJHR-SSDOTTSWSA-M (2r)-2-ethylhexanoate Chemical compound CCCC[C@@H](CC)C([O-])=O OBETXYAYXDNJHR-SSDOTTSWSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 238000010936 aqueous wash Methods 0.000 description 1
- 239000003781 beta lactamase inhibitor Substances 0.000 description 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000010587 phase diagram Methods 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
-
- 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
- C07D498/02—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 two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Cephalosporin Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0011519 | 2000-05-13 | ||
| GB0011519A GB0011519D0 (en) | 2000-05-13 | 2000-05-13 | Process |
| GB0011521A GB0011521D0 (en) | 2000-05-13 | 2000-05-13 | Process |
| GB0011521 | 2000-05-13 | ||
| PCT/GB2001/002025 WO2001087891A1 (en) | 2000-05-13 | 2001-05-09 | Process for the purification of a salt of clavulanic acid |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE60105016D1 DE60105016D1 (de) | 2004-09-23 |
| DE60105016T2 DE60105016T2 (de) | 2005-08-18 |
| DE60105016T3 true DE60105016T3 (de) | 2009-06-25 |
Family
ID=26244256
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60105016T Expired - Lifetime DE60105016T3 (de) | 2000-05-13 | 2001-05-09 | Verfahren zur reinigung eines salzes der clavulansäure |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7767823B2 (enExample) |
| EP (1) | EP1284978B2 (enExample) |
| JP (1) | JP4954421B2 (enExample) |
| KR (1) | KR100827898B1 (enExample) |
| CN (1) | CN1222528C (enExample) |
| AT (1) | ATE273982T1 (enExample) |
| AU (1) | AU776184B2 (enExample) |
| BR (1) | BRPI0110774B8 (enExample) |
| CA (1) | CA2408853C (enExample) |
| CZ (1) | CZ304775B6 (enExample) |
| DE (1) | DE60105016T3 (enExample) |
| DK (1) | DK1284978T4 (enExample) |
| ES (1) | ES2225524T5 (enExample) |
| HU (1) | HU228593B1 (enExample) |
| IL (2) | IL152643A0 (enExample) |
| MX (1) | MXPA02011192A (enExample) |
| NO (1) | NO328528B1 (enExample) |
| NZ (1) | NZ522414A (enExample) |
| PL (1) | PL206316B1 (enExample) |
| PT (1) | PT1284978E (enExample) |
| SI (1) | SI1284978T2 (enExample) |
| WO (1) | WO2001087891A1 (enExample) |
| ZA (1) | ZA200209141B (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1284978E (pt) | 2000-05-13 | 2004-12-31 | Smithkline Beecham Plc | Processo para a purificacao de um sal de acido clavulanico |
| CN105384758B (zh) * | 2015-12-01 | 2018-05-01 | 国药集团威奇达药业有限公司 | 克拉维酸胺盐的制备方法 |
| SG11201811345TA (en) | 2016-07-14 | 2019-01-30 | Achaogen Inc | Combination of ceftibuten and clavulanic acid for use in the treatment of bacterial infections |
| CN109305978A (zh) * | 2017-07-26 | 2019-02-05 | 山东睿鹰先锋制药有限公司 | 一种制备克拉维酸盐的新方法 |
| CN109535184B (zh) * | 2017-09-21 | 2020-11-20 | 联邦制药(内蒙古)有限公司 | 一种克拉维酸叔辛胺制备克拉维酸钾的方法 |
| CN108558909B (zh) * | 2018-05-17 | 2019-09-17 | 国药集团威奇达药业有限公司 | 综合回收克拉维酸叔丁胺盐结晶母液中有效成分的方法 |
| EP3994154A1 (en) | 2019-07-05 | 2022-05-11 | GlaxoSmithKline Intellectual Property (No.2) Limited | Streptomyces clavuligerus |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1299883A (fr) | 1961-09-06 | 1962-07-27 | Pfizer & Co C | Perfectionnements apportés aux procédés pour séparer des amino-acides amphotères de leurs solutions aqueuses |
| GB1508977A (en) | 1974-04-20 | 1978-04-26 | Beecham Group Ltd | Beta-lactam antibiotic from streptomyces clavuligerus |
| GB2003863B (en) | 1977-09-01 | 1982-03-31 | Beecham Group Ltd | Chemical process |
| EP0026044B1 (en) | 1979-08-24 | 1983-06-08 | Beecham Group Plc | Amine salt of clavulanic acid, its preparation and use |
| US4449182A (en) * | 1981-10-05 | 1984-05-15 | Digital Equipment Corporation | Interface between a pair of processors, such as host and peripheral-controlling processors in data processing systems |
| NZ213963A (en) | 1984-10-27 | 1989-01-06 | Antibioticos Sa | Production of clavulanic acid |
| DE3853962T2 (de) | 1987-01-29 | 1996-02-08 | Beecham Group Plc | Verfahren zur Kristallisation von Kalium-Clavulanat. |
| GB2204944B (en) | 1987-05-18 | 1991-10-02 | Frederick John Anderson | Rechargeable light |
| DE3729338A1 (de) | 1987-09-02 | 1989-03-23 | Biotechnolog Forschung Gmbh | Verfahren zur abtrennung von penicillin g aus einem fermentationsmedium durch extraktion |
| US5318896A (en) | 1991-09-11 | 1994-06-07 | Merck & Co., Inc. | Recombinant expandase bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid (7-ADCA) |
| KR100227711B1 (ko) | 1991-10-15 | 1999-12-01 | 한스 발터 라벤 | 7-아미노세팔로스포란산 및 7-아미노데아세틸세팔로스포란산 제조를 위한 신규한 생물학적 공정 |
| AT400033B (de) * | 1992-03-10 | 1995-09-25 | Biochemie Gmbh | Neues verfahren zur isolierung und reinigung von clavulansäure und zur herstellung von pharmakologisch verträglichen salzen derselben |
| SI9300296B (sl) | 1992-06-11 | 1998-06-30 | Smithkline Beecham P.L.C. | Postopek in intermedianti za pripravo klavulanske kisline |
| KR100200239B1 (ko) * | 1992-10-21 | 1999-06-15 | 김충환 | 클라불란산 칼륨염의 제조방법 |
| GB9305565D0 (en) | 1993-03-18 | 1993-05-05 | Smithkline Beecham Plc | Novel compounds and processes |
| US5821364A (en) * | 1993-03-26 | 1998-10-13 | Gist-Brocades N.V. | Diamine salts of clavulanic acid |
| HU219259B (en) | 1993-07-30 | 2001-03-28 | Gist Brocades Bv | Process for the efficient production of 7-adca via 2-(carboxyethylthio)acetyl-7-adca and 3-(carboxymethylthio)propionyl-7-adca, recombinant dna vectrors and transformed host cells |
| AT400846B (de) | 1994-02-25 | 1996-03-25 | Fermic S A De C V | Verfahren zur gewinnung und reinigung von alkalimetallsalzen der clavulansäure |
| SI9400107A (en) | 1994-03-02 | 1995-10-31 | Lek Tovarna Farmacevtskih | New process of the isolation of clavulanic acid and its pharmaceutical salts from fermented broth of streptomyces sp.p 6621 ferm p 2804. |
| GB9426261D0 (en) | 1994-12-24 | 1995-02-22 | Spurcourt Ltd | Clavulanic acid salts |
| SI9500074A (en) | 1995-03-10 | 1996-10-31 | Lek Tovarna Farmacevtskih | Process for preparation of alkani salts of clavulanic acid. |
| SI9500134B (sl) | 1995-04-20 | 2004-04-30 | Lek, | Postopek za pripravo čistih alkalijskih soli klavulanske kisline |
| KR100200242B1 (ko) | 1995-05-16 | 1999-06-15 | 김충환 | 클라불란산염의 제조 방법 |
| WO1997005143A1 (en) * | 1995-07-25 | 1997-02-13 | Asahi Kasei Kogyo Kabushiki Kaisha | Novel group 4 transition metal compounds |
| GB9515809D0 (en) * | 1995-08-02 | 1995-10-04 | Smithkline Beecham Plc | Process |
| AU5551698A (en) * | 1996-11-11 | 1998-06-03 | Gist-Brocades B.V. | Process for the preparation of salts and esters of clavulanic acid |
| AT404728B (de) * | 1996-11-27 | 1999-02-25 | Biochemie Gmbh | Verfahren zur herstellung von clavulansäure-aminsalzen |
| WO1998042858A1 (en) | 1997-03-24 | 1998-10-01 | Cipan-Companhia Industrial Produtora De Antibióticos, S.A. | Process for the isolation of a pharmaceutically acceptable alkali metal salt of clavulanic acid |
| ES2237840T3 (es) * | 1997-04-22 | 2005-08-01 | Dsm Ip Assets B.V. | Proceso mejorado para la produccion fermentativa de cefalosporina. |
| AU5411099A (en) * | 1998-07-16 | 2000-02-07 | Dsm N.V. | Improved process for the preparation of salts and esters of clavulanic acid |
| PT1284978E (pt) | 2000-05-13 | 2004-12-31 | Smithkline Beecham Plc | Processo para a purificacao de um sal de acido clavulanico |
-
2001
- 2001-05-09 PT PT01925753T patent/PT1284978E/pt unknown
- 2001-05-09 US US10/275,852 patent/US7767823B2/en not_active Expired - Lifetime
- 2001-05-09 CN CNB018094236A patent/CN1222528C/zh not_active Expired - Lifetime
- 2001-05-09 AT AT01925753T patent/ATE273982T1/de active
- 2001-05-09 DE DE60105016T patent/DE60105016T3/de not_active Expired - Lifetime
- 2001-05-09 CZ CZ2002-3723A patent/CZ304775B6/cs not_active IP Right Cessation
- 2001-05-09 KR KR1020027015169A patent/KR100827898B1/ko not_active Expired - Lifetime
- 2001-05-09 WO PCT/GB2001/002025 patent/WO2001087891A1/en not_active Ceased
- 2001-05-09 JP JP2001584285A patent/JP4954421B2/ja not_active Expired - Lifetime
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- 2001-05-09 BR BRPI0110774A patent/BRPI0110774B8/pt not_active IP Right Cessation
- 2001-05-09 DK DK01925753T patent/DK1284978T4/da active
- 2001-05-09 AU AU52432/01A patent/AU776184B2/en not_active Expired
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- 2001-05-09 CA CA2408853A patent/CA2408853C/en not_active Expired - Lifetime
- 2001-05-09 HU HU0300869A patent/HU228593B1/hu unknown
- 2001-05-09 SI SI200130207T patent/SI1284978T2/sl unknown
- 2001-05-09 ES ES01925753T patent/ES2225524T5/es not_active Expired - Lifetime
- 2001-05-09 IL IL15264301A patent/IL152643A0/xx unknown
- 2001-05-09 MX MXPA02011192A patent/MXPA02011192A/es active IP Right Grant
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2002
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