FI111949B - Menetelmä kaliumklavulanaatin valmistamiseksi - Google Patents
Menetelmä kaliumklavulanaatin valmistamiseksi Download PDFInfo
- Publication number
- FI111949B FI111949B FI963050A FI963050A FI111949B FI 111949 B FI111949 B FI 111949B FI 963050 A FI963050 A FI 963050A FI 963050 A FI963050 A FI 963050A FI 111949 B FI111949 B FI 111949B
- Authority
- FI
- Finland
- Prior art keywords
- solution
- water
- clavulanic acid
- potassium
- organic solvent
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 83
- 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 title claims description 36
- 238000002360 preparation method Methods 0.000 title claims description 8
- 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 description 88
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 78
- 229960003324 clavulanic acid Drugs 0.000 claims description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 53
- 229910001868 water Inorganic materials 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 45
- 239000003960 organic solvent Substances 0.000 claims description 44
- 239000008346 aqueous phase Substances 0.000 claims description 37
- 239000002243 precursor Substances 0.000 claims description 28
- 238000002156 mixing Methods 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 21
- 238000000926 separation method Methods 0.000 claims description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 17
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 16
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 13
- 229910052700 potassium Inorganic materials 0.000 claims description 12
- 239000011591 potassium Substances 0.000 claims description 12
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 11
- ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical group [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 claims description 11
- 239000007787 solid Substances 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 4
- 238000005119 centrifugation Methods 0.000 claims description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 4
- 239000012736 aqueous medium Substances 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims 1
- 210000003109 clavicle Anatomy 0.000 claims 1
- 239000000243 solution Substances 0.000 description 52
- 239000000203 mixture Substances 0.000 description 18
- 239000007864 aqueous solution Substances 0.000 description 16
- 239000012071 phase Substances 0.000 description 16
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 12
- -1 clavulanic acid ester Chemical class 0.000 description 10
- 229960003975 potassium Drugs 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 239000000839 emulsion Substances 0.000 description 8
- 239000012530 fluid Substances 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 238000000605 extraction Methods 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 229940090805 clavulanate Drugs 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000000638 solvent extraction Methods 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 238000005191 phase separation Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 241000187433 Streptomyces clavuligerus Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 239000003781 beta lactamase inhibitor Substances 0.000 description 2
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 2
- 235000019797 dipotassium phosphate Nutrition 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012527 feed solution Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 235000014366 other mixer Nutrition 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000011800 void material Substances 0.000 description 2
- 229940126085 β‑Lactamase Inhibitor Drugs 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
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 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
- 229960003022 amoxicillin Drugs 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000037427 ion transport Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 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 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 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
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 1
- 229960004659 ticarcillin Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 239000002699 waste material 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9401969A GB9401969D0 (en) | 1994-02-02 | 1994-02-02 | Process |
| GB9401969 | 1994-02-02 | ||
| PCT/GB1995/000191 WO1995021173A1 (en) | 1994-02-02 | 1995-01-31 | Process for the preparation of a salt of clavulanic acid |
| GB9500191 | 1995-01-31 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI963050A0 FI963050A0 (fi) | 1996-08-01 |
| FI963050L FI963050L (fi) | 1996-10-01 |
| FI111949B true FI111949B (fi) | 2003-10-15 |
Family
ID=10749727
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI963050A FI111949B (fi) | 1994-02-02 | 1996-08-01 | Menetelmä kaliumklavulanaatin valmistamiseksi |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US5965728A (cs) |
| EP (1) | EP0741732B1 (cs) |
| JP (1) | JP4074336B2 (cs) |
| KR (1) | KR100388769B1 (cs) |
| CN (1) | CN1065246C (cs) |
| AP (1) | AP610A (cs) |
| AT (1) | ATE202358T1 (cs) |
| AU (1) | AU688849B2 (cs) |
| BG (1) | BG63307B1 (cs) |
| BR (1) | BR9506919A (cs) |
| CA (1) | CA2182504C (cs) |
| CZ (1) | CZ294005B6 (cs) |
| DE (1) | DE69521415T2 (cs) |
| DK (1) | DK0741732T3 (cs) |
| ES (1) | ES2159626T3 (cs) |
| FI (1) | FI111949B (cs) |
| GB (1) | GB9401969D0 (cs) |
| GR (1) | GR3036602T3 (cs) |
| HU (1) | HU226597B1 (cs) |
| MX (1) | MX9603204A (cs) |
| NO (1) | NO314505B1 (cs) |
| NZ (1) | NZ278927A (cs) |
| OA (1) | OA10587A (cs) |
| PL (1) | PL181451B1 (cs) |
| PT (1) | PT741732E (cs) |
| RO (1) | RO115730B1 (cs) |
| RU (1) | RU2140418C1 (cs) |
| SI (1) | SI0741732T1 (cs) |
| SK (1) | SK282544B6 (cs) |
| UA (1) | UA48944C2 (cs) |
| WO (1) | WO1995021173A1 (cs) |
Families Citing this family (13)
| 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 |
| 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. |
| GB9500977D0 (en) * | 1995-01-19 | 1995-03-08 | Smithkline Beecham Plc | Novel process |
| SI9500134B (sl) * | 1995-04-20 | 2004-04-30 | Lek, | Postopek za pripravo čistih alkalijskih soli klavulanske kisline |
| GB9515809D0 (en) * | 1995-08-02 | 1995-10-04 | Smithkline Beecham Plc | Process |
| AT403375B (de) * | 1995-11-15 | 1998-01-26 | Biochemie Gmbh | Verfahren zur fällung von alkalisalzen der clavulansäure |
| US6414142B1 (en) * | 1996-06-13 | 2002-07-02 | Smithkline Beecham Corporation | Process for preparing potassium clavulanate |
| 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 |
| ATE187498T1 (de) | 1997-03-24 | 1999-12-15 | Cipan Comp Ind Prod | Verfahren zur isolierung eines pharmazeutisch verträglichen alkalimetallsalzes der clavulansäure |
| DZ2456A1 (fr) * | 1997-04-04 | 2003-01-18 | Smithkline Beecham Plc | Procédé de préparation de sels de l'acide clavulanique. |
| US7199242B2 (en) | 2001-08-02 | 2007-04-03 | Lg Life Sciences Limited | Processes for the production of amino-protected derivatives of 4-aminomethylene-pyrrolidin-3-one and/or 4-aminomethylene-pyrrolidin-3-alkoxyimino derivatives and/or gemifloxacin or a salt thereof |
| CA3028452A1 (en) | 2016-07-14 | 2018-01-18 | Achaogen Inc. | Combination of ceftibuten and clavulanic acid for use in the treatment of bacterial infections |
| CN108822134B (zh) * | 2018-04-25 | 2021-06-25 | 国药集团威奇达药业有限公司 | 克拉维酸叔丁胺盐的制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1508977A (en) * | 1974-04-20 | 1978-04-26 | Beecham Group Ltd | Beta-lactam antibiotic from streptomyces clavuligerus |
| ES444195A1 (es) * | 1974-10-09 | 1977-08-01 | Beecham Group Ltd | Un procedimiento para la preparacion de acido clavulanico. |
| GB1543563A (en) * | 1975-02-07 | 1979-04-04 | Glaxo Lab Ltd | Beta-lactam antibiotic in purified form |
| GB1563103A (en) * | 1975-10-13 | 1980-03-19 | Beecham Group Ltd | Process for the preparation 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 |
| GB8404749D0 (en) * | 1984-02-23 | 1984-03-28 | Atomic Energy Authority Uk | Fluidic contactor |
| ES2010143A6 (es) * | 1989-03-01 | 1989-10-16 | Pharma Mar S A Pharmar | Un nuevo procedimiento de obtencion del acido z(2r,5r)-3-(2-hiadroxietiliden)-7- oxo-4-oxa-1-azabiciclo(3,2,0) -heptano-2-carboxilico y de sales estares farmaceutiacamente aceptables del mismo,a partir de caldos de fermentacion de streptomyces, sp. |
-
1994
- 1994-02-02 GB GB9401969A patent/GB9401969D0/en active Pending
-
1995
- 1995-01-31 RU RU96117347A patent/RU2140418C1/ru not_active IP Right Cessation
- 1995-01-31 MX MX9603204A patent/MX9603204A/es not_active IP Right Cessation
- 1995-01-31 KR KR1019960704202A patent/KR100388769B1/ko not_active Expired - Fee Related
- 1995-01-31 BR BR9506919A patent/BR9506919A/pt not_active Application Discontinuation
- 1995-01-31 PT PT95907075T patent/PT741732E/pt unknown
- 1995-01-31 AU AU15412/95A patent/AU688849B2/en not_active Ceased
- 1995-01-31 WO PCT/GB1995/000191 patent/WO1995021173A1/en not_active Ceased
- 1995-01-31 DE DE69521415T patent/DE69521415T2/de not_active Expired - Lifetime
- 1995-01-31 ES ES95907075T patent/ES2159626T3/es not_active Expired - Lifetime
- 1995-01-31 PL PL95315782A patent/PL181451B1/pl not_active IP Right Cessation
- 1995-01-31 CA CA002182504A patent/CA2182504C/en not_active Expired - Fee Related
- 1995-01-31 HU HU9602128A patent/HU226597B1/hu not_active IP Right Cessation
- 1995-01-31 SK SK1003-96A patent/SK282544B6/sk not_active IP Right Cessation
- 1995-01-31 DK DK95907075T patent/DK0741732T3/da active
- 1995-01-31 NZ NZ278927A patent/NZ278927A/en not_active IP Right Cessation
- 1995-01-31 CZ CZ19962294A patent/CZ294005B6/cs not_active IP Right Cessation
- 1995-01-31 EP EP95907075A patent/EP0741732B1/en not_active Expired - Lifetime
- 1995-01-31 AT AT95907075T patent/ATE202358T1/de not_active IP Right Cessation
- 1995-01-31 SI SI9530525T patent/SI0741732T1/xx unknown
- 1995-01-31 AP APAP/P/1996/000838A patent/AP610A/en active
- 1995-01-31 CN CN95192179A patent/CN1065246C/zh not_active Expired - Fee Related
- 1995-01-31 JP JP52044595A patent/JP4074336B2/ja not_active Expired - Fee Related
- 1995-01-31 US US08/663,158 patent/US5965728A/en not_active Expired - Lifetime
- 1995-01-31 RO RO96-01582A patent/RO115730B1/ro unknown
- 1995-01-31 UA UA96083392A patent/UA48944C2/uk unknown
-
1996
- 1996-08-01 FI FI963050A patent/FI111949B/fi active
- 1996-08-01 BG BG100765A patent/BG63307B1/bg unknown
- 1996-08-01 NO NO19963217A patent/NO314505B1/no not_active IP Right Cessation
- 1996-08-02 OA OA60872A patent/OA10587A/en unknown
-
2001
- 2001-09-12 GR GR20010401463T patent/GR3036602T3/el not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI111949B (fi) | Menetelmä kaliumklavulanaatin valmistamiseksi | |
| BG62213B1 (bg) | Нов метод за изолиране на клавуланова киселина и нейнитефармацевтично приемливи соли от ферментационна хранителна среда наstreptomyces sp. p 6621 ferm p 2804 | |
| JPH11503744A (ja) | クラブラン酸塩の製造方法 | |
| RU2169151C2 (ru) | Способ получения и/или очистки клавулановой кислоты из ферментационного бульона посредством ультрафильтрации | |
| KR100446199B1 (ko) | 클라불란산추출방법 | |
| HK1012373B (en) | Process for the preparation of a salt of clavulanic acid | |
| AU706196C (en) | Clavulanic acid extraction process |