CZ297065B6 - Hydrochlorid valacykloviru v bezvodé krystalické forme a zpusob jeho výroby - Google Patents
Hydrochlorid valacykloviru v bezvodé krystalické forme a zpusob jeho výroby Download PDFInfo
- Publication number
- CZ297065B6 CZ297065B6 CZ0229497A CZ229497A CZ297065B6 CZ 297065 B6 CZ297065 B6 CZ 297065B6 CZ 0229497 A CZ0229497 A CZ 0229497A CZ 229497 A CZ229497 A CZ 229497A CZ 297065 B6 CZ297065 B6 CZ 297065B6
- Authority
- CZ
- Czechia
- Prior art keywords
- valaciclovir hydrochloride
- valaciclovir
- crystalline form
- hydrochloride
- weight
- Prior art date
Links
- ZCDDBUOENGJMLV-QRPNPIFTSA-N Valacyclovir hydrochloride Chemical compound Cl.N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 ZCDDBUOENGJMLV-QRPNPIFTSA-N 0.000 title claims description 71
- 238000000034 method Methods 0.000 title claims description 22
- 238000002360 preparation method Methods 0.000 title claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 239000002904 solvent Substances 0.000 claims description 21
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 claims description 18
- 229940093257 valacyclovir Drugs 0.000 claims description 16
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 11
- 238000009826 distribution Methods 0.000 claims description 9
- 230000003381 solubilizing effect Effects 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000012458 free base Substances 0.000 claims description 6
- 150000002576 ketones Chemical class 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 150000003839 salts Chemical group 0.000 claims description 6
- 238000010586 diagram Methods 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000013557 residual solvent Substances 0.000 claims description 2
- 206010019972 Herpes viral infections Diseases 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract description 5
- PQGVTLQEKCJXKF-RGMNGODLSA-N ethyl (2s)-2-amino-3-methylbutanoate;hydron;chloride Chemical compound Cl.CCOC(=O)[C@@H](N)C(C)C PQGVTLQEKCJXKF-RGMNGODLSA-N 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- -1 compound valaciclovir hydrochloride Chemical class 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 9
- 229960004150 aciclovir Drugs 0.000 description 8
- 239000011928 denatured alcohol Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-Valine Natural products CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 7
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000002441 X-ray diffraction Methods 0.000 description 6
- 230000000840 anti-viral effect Effects 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 229960004295 valine Drugs 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
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- 239000000126 substance Substances 0.000 description 4
- 238000005292 vacuum distillation Methods 0.000 description 4
- 208000009889 Herpes Simplex Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000000306 component Substances 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
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- 239000000706 filtrate Substances 0.000 description 3
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- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229940069328 povidone Drugs 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 208000007514 Herpes zoster Diseases 0.000 description 2
- 241000701027 Human herpesvirus 6 Species 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
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- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
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- 230000003612 virological effect Effects 0.000 description 2
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000001688 Herpes Genitalis Diseases 0.000 description 1
- 206010019973 Herpes virus infection Diseases 0.000 description 1
- 241000175212 Herpesvirales Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 238000003109 Karl Fischer titration Methods 0.000 description 1
- 101000870363 Oryctolagus cuniculus Glutathione S-transferase Yc Proteins 0.000 description 1
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- 208000005181 Varicella Zoster Virus Infection Diseases 0.000 description 1
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- 125000003158 alcohol group Chemical group 0.000 description 1
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- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
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- 239000007937 lozenge Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- 238000000465 moulding Methods 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
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- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
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- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229940064636 valacyclovir hydrochloride Drugs 0.000 description 1
- 208000010531 varicella zoster infection Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
- 229960002555 zidovudine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- 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
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9501178.9A GB9501178D0 (en) | 1995-01-20 | 1995-01-20 | Guanine derivative |
| PCT/GB1996/000117 WO1996022291A1 (en) | 1995-01-20 | 1996-01-19 | Guanine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ229497A3 CZ229497A3 (en) | 1997-12-17 |
| CZ297065B6 true CZ297065B6 (cs) | 2006-08-16 |
Family
ID=10768347
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ0229497A CZ297065B6 (cs) | 1995-01-20 | 1996-01-19 | Hydrochlorid valacykloviru v bezvodé krystalické forme a zpusob jeho výroby |
Country Status (40)
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9501178D0 (en) * | 1995-01-20 | 1995-03-08 | Wellcome Found | Guanine derivative |
| AU722304B2 (en) * | 1996-01-19 | 2000-07-27 | Glaxo Group Limited | Use of valaciclovir for the manufacture of a medicament for the treatment of genital herpes by a single daily application |
| IT1283447B1 (it) * | 1996-07-18 | 1998-04-21 | Ind Chimica Srl | Processo di preparazione del valaciclovir e relativi intermedi |
| WO1998031683A1 (fr) * | 1997-01-17 | 1998-07-23 | Ajinomoto Co., Inc. | Nouveaux cristaux de z-valacyclovir |
| GB0010446D0 (en) * | 2000-04-28 | 2000-06-14 | Glaxo Wellcome Kk | Pharmaceutical formulation |
| HU230382B1 (hu) * | 2001-02-24 | 2016-03-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xantinszármazékok, előállításuk és alkalmazásuk gyógyszerként |
| CZ2004446A3 (cs) * | 2001-09-07 | 2005-01-12 | Teva Pharmaceutical Industries Ltd. | Krystalické formy valaciklovir hydrochloridu |
| EP1453834A1 (en) * | 2001-11-05 | 2004-09-08 | Glaxo Group Limited | Anhydrous crystal form of valaciclovir hydrochloride |
| US6849737B2 (en) * | 2001-11-14 | 2005-02-01 | Teva Pharmaceutical Industries Ltd. | Synthesis and purification of valacyclovir |
| EP1517678A2 (en) * | 2002-06-24 | 2005-03-30 | Ranbaxy Laboratories Limited | Process for the preparation of robust formulations of valacyclovir hydrochloride tablets |
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| US20050043329A1 (en) * | 2002-09-06 | 2005-02-24 | Shlomit Wizel | Crystalline forms of valacyclovir hydrochloride |
| US20050059684A1 (en) * | 2002-10-16 | 2005-03-17 | Ben-Zion Dolitzky | Method for reducing residual alcohols in crystalline valacyclovir hydrochloride |
| AU2003277433A1 (en) * | 2002-10-16 | 2004-05-04 | Teva Pharmaceutical Industries Ltd. | Method for reducing residual alcohols in crystalline valacyclovir hydrochloride |
| AU2003289995A1 (en) * | 2002-12-09 | 2004-06-30 | Texcontor Etablissement | Anhydrous crystalline form of valacyclovir hydrochloride |
| US7786302B2 (en) * | 2003-05-30 | 2010-08-31 | Eczacibasi-Zentiva Kimyasal Urunler Sanayi Ve Ticaret A.S. | Crystalline forms of valacyclovir hydrochloride |
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Legal Events
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| PD00 | Pending as of 2000-06-30 in czech republic | ||
| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20110119 |