HRP960186A2 - Preparation of clavulanate salts - Google Patents
Preparation of clavulanate salts Download PDFInfo
- Publication number
- HRP960186A2 HRP960186A2 HRP9500134A HRP960186A HRP960186A2 HR P960186 A2 HRP960186 A2 HR P960186A2 HR P9500134 A HRP9500134 A HR P9500134A HR P960186 A HRP960186 A HR P960186A HR P960186 A2 HRP960186 A2 HR P960186A2
- Authority
- HR
- Croatia
- Prior art keywords
- clavulanic acid
- diamine
- methanol
- amine
- group
- Prior art date
Links
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical class OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title description 12
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims abstract description 65
- 229960003324 clavulanic acid Drugs 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 24
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 150000001412 amines Chemical class 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- -1 amine salt Chemical class 0.000 claims abstract description 11
- 150000002148 esters Chemical class 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 111
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 63
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 45
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 42
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 28
- 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 claims description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 10
- DLSOILHAKCBARI-UHFFFAOYSA-N n-benzyl-2-methylpropan-2-amine Chemical compound CC(C)(C)NCC1=CC=CC=C1 DLSOILHAKCBARI-UHFFFAOYSA-N 0.000 claims description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 6
- 150000004985 diamines Chemical class 0.000 claims description 6
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 6
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- BHRZNVHARXXAHW-UHFFFAOYSA-N sec-butylamine Chemical compound CCC(C)N BHRZNVHARXXAHW-UHFFFAOYSA-N 0.000 claims description 4
- GAHCNYHAKKGGHF-UHFFFAOYSA-N 5,5-dimethylhexan-1-amine Chemical compound CC(C)(C)CCCCN GAHCNYHAKKGGHF-UHFFFAOYSA-N 0.000 claims description 3
- CJKRXEBLWJVYJD-UHFFFAOYSA-N N,N'-diethylethylenediamine Chemical compound CCNCCNCC CJKRXEBLWJVYJD-UHFFFAOYSA-N 0.000 claims description 3
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 229910001573 adamantine Inorganic materials 0.000 claims 1
- 238000000746 purification Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 28
- 238000004458 analytical method Methods 0.000 description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- 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 description 10
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 238000000855 fermentation Methods 0.000 description 6
- 230000004151 fermentation Effects 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000002024 ethyl acetate extract Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 241000187747 Streptomyces Species 0.000 description 3
- 229940090805 clavulanate Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 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
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- NMPWOLAIBCYZEP-WUJLRWPWSA-N Clavam-2-carboxylate Chemical compound O1[C@@H](C(=O)O)CN2C(=O)C[C@@H]21 NMPWOLAIBCYZEP-WUJLRWPWSA-N 0.000 description 2
- NMPWOLAIBCYZEP-UHFFFAOYSA-N Clavam-2-carboxylate Natural products O1C(C(=O)O)CN2C(=O)CC21 NMPWOLAIBCYZEP-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000011097 chromatography purification Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001471 micro-filtration Methods 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- MDXHGUSIQTUIEV-UHFFFAOYSA-N 1-n,1-n,2-n,2-n-tetramethylbutane-1,2-diamine Chemical compound CCC(N(C)C)CN(C)C MDXHGUSIQTUIEV-UHFFFAOYSA-N 0.000 description 1
- NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000424942 Streptomyces clavuligerus ATCC 27064 Species 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 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
- 150000007513 acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229960004920 amoxicillin trihydrate Drugs 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 239000003781 beta lactamase inhibitor Substances 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 1
- 150000002171 ethylene diamines Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 159000000011 group IA salts Chemical class 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical class CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- JMRXTGCDVQLAFM-JSYANWSFSA-M lithium;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Li+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 JMRXTGCDVQLAFM-JSYANWSFSA-M 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D503/00—Heterocyclic compounds containing 4-oxa-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxapenicillins, clavulanic acid derivatives; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Veterinary Medicine (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)
- Saccharide Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI9500134A SI9500134B (sl) | 1995-04-20 | 1995-04-20 | Postopek za pripravo čistih alkalijskih soli klavulanske kisline |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP960186A2 true HRP960186A2 (en) | 1997-12-31 |
Family
ID=20431603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP9500134A HRP960186A2 (en) | 1995-04-20 | 1996-04-19 | Preparation of clavulanate salts |
Country Status (29)
| Country | Link |
|---|---|
| US (2) | US6180782B1 (uk) |
| EP (1) | EP0821687B1 (uk) |
| JP (1) | JPH11503744A (uk) |
| KR (1) | KR19990007892A (uk) |
| CN (1) | CN1118469C (uk) |
| AT (1) | ATE239736T1 (uk) |
| BG (1) | BG63395B1 (uk) |
| CA (1) | CA2218648A1 (uk) |
| CZ (1) | CZ293279B6 (uk) |
| DE (1) | DE69628002T2 (uk) |
| DK (1) | DK0821687T3 (uk) |
| DZ (1) | DZ2024A1 (uk) |
| EE (1) | EE9700263A (uk) |
| EG (1) | EG21091A (uk) |
| ES (1) | ES2199286T3 (uk) |
| HR (1) | HRP960186A2 (uk) |
| HU (1) | HUP9901055A3 (uk) |
| JO (1) | JO1902B1 (uk) |
| PL (1) | PL183465B1 (uk) |
| PT (1) | PT821687E (uk) |
| RO (1) | RO116195B1 (uk) |
| RU (1) | RU2166506C2 (uk) |
| SI (1) | SI9500134B (uk) |
| SK (1) | SK143797A3 (uk) |
| TN (1) | TNSN96061A1 (uk) |
| UA (1) | UA54389C2 (uk) |
| WO (1) | WO1996033197A1 (uk) |
| YU (1) | YU49113B (uk) |
| ZA (1) | ZA963119B (uk) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| SI9500134B (sl) * | 1995-04-20 | 2004-04-30 | Lek, | Postopek za pripravo čistih alkalijskih soli klavulanske kisline |
| SI9500265A1 (en) * | 1995-08-28 | 1997-02-28 | Lek Tovarna Farmacevtskih | Process for purification of the aqueous fermented broth filtrate of streptomyces sp. p 6621 ferm p 2804 by ultrafiltration |
| AT403375B (de) * | 1995-11-15 | 1998-01-26 | Biochemie Gmbh | Verfahren zur fällung von alkalisalzen der clavulansäure |
| CN1238776A (zh) * | 1996-11-11 | 1999-12-15 | 吉斯特-布罗卡迪斯有限公司 | 制备棒酸盐和酯的方法 |
| AT404728B (de) * | 1996-11-27 | 1999-02-25 | Biochemie Gmbh | Verfahren zur herstellung von clavulansäure-aminsalzen |
| AR015825A1 (es) * | 1997-05-28 | 2001-05-30 | Gist Brocades Bv | Produccion fermentativa de acido clavulanico bajo condiciones controladas de fosfato |
| GB0003305D0 (en) | 2000-02-15 | 2000-04-05 | Zeneca Ltd | Pyrimidine derivatives |
| US20040146918A1 (en) * | 2000-02-18 | 2004-07-29 | Weiner Michael L. | Hybrid nucleic acid assembly |
| ES2225524T5 (es) | 2000-05-13 | 2009-03-01 | Smithkline Beecham Plc | Procedimiento para la purificacion de una 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 |
| 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 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4110165A (en) | 1974-04-20 | 1978-08-29 | Beecham Group Limited | Process for the production of clavulanic acid |
| US4144242A (en) | 1975-02-07 | 1979-03-13 | Glaxo Laboratories Limited | Process for the purification of clavulanic acid |
| GB1578739A (en) | 1976-07-23 | 1980-11-05 | Beecham Group Ltd | Amine salts of clavulanic acid methods for their preparation and compositions containing them |
| EP0026044B1 (en) | 1979-08-24 | 1983-06-08 | Beecham Group Plc | Amine salt of clavulanic acid, its preparation and use |
| US4454069A (en) | 1979-08-24 | 1984-06-12 | Beecham Group Limited | Clavulanic acid salts and their preparation from the tertiary butyl amine salt |
| MX7417E (es) * | 1984-10-27 | 1988-10-14 | Antibioticos Sa | Metodo para la preparacion de acido clavulanico y sus derivados |
| AT399155B (de) * | 1992-03-26 | 1995-03-27 | Lek Tovarna Farmacevtskih | Neue alkylendiammonium-diclavulanat-derivate, verfahren zu deren herstellung sowie deren verwendung |
| 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 |
| RO112113B1 (ro) | 1993-03-26 | 1997-05-30 | Gist Brocades Nv | Saruri diaminice ale acidului clavulanic si procedeu pentru prepararea acestora |
| GB9401969D0 (en) * | 1994-02-02 | 1994-03-30 | Smithkline Beecham Plc | Process |
| 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 |
| WO1996026944A1 (en) * | 1995-02-25 | 1996-09-06 | Spurcourt Limited | 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 |
| CN1238776A (zh) * | 1996-11-11 | 1999-12-15 | 吉斯特-布罗卡迪斯有限公司 | 制备棒酸盐和酯的方法 |
-
1995
- 1995-04-20 SI SI9500134A patent/SI9500134B/sl not_active IP Right Cessation
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1996
- 1996-04-17 ES ES96910095T patent/ES2199286T3/es not_active Expired - Lifetime
- 1996-04-17 JP JP8531550A patent/JPH11503744A/ja not_active Ceased
- 1996-04-17 PT PT96910095T patent/PT821687E/pt unknown
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- 1996-04-17 HU HU9901055A patent/HUP9901055A3/hu unknown
- 1996-04-17 AT AT96910095T patent/ATE239736T1/de active
- 1996-04-17 UA UA97105123A patent/UA54389C2/uk unknown
- 1996-04-17 EP EP96910095A patent/EP0821687B1/en not_active Expired - Lifetime
- 1996-04-17 WO PCT/GB1996/000921 patent/WO1996033197A1/en active IP Right Grant
- 1996-04-17 CN CN96194125A patent/CN1118469C/zh not_active Expired - Fee Related
- 1996-04-17 CA CA002218648A patent/CA2218648A1/en not_active Abandoned
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- 1996-04-17 RO RO97-01936A patent/RO116195B1/ro unknown
- 1996-04-17 US US08/930,527 patent/US6180782B1/en not_active Expired - Lifetime
- 1996-04-17 DE DE69628002T patent/DE69628002T2/de not_active Expired - Lifetime
- 1996-04-17 SK SK1437-97A patent/SK143797A3/sk unknown
- 1996-04-19 TN TNTNSN96061A patent/TNSN96061A1/fr unknown
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- 1996-04-19 YU YU24796A patent/YU49113B/sh unknown
- 1996-04-19 HR HRP9500134A patent/HRP960186A2/hr not_active Application Discontinuation
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- 1996-04-20 JO JO19961902A patent/JO1902B1/en active
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