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
- 239000003054 catalyst Substances 0.000 description 5
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- 230000009385 viral infection Effects 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
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- 238000009472 formulation Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 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
- 239000008358 core component Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 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
- 239000000969 carrier Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
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- 229910052802 copper Inorganic materials 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 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
- 239000002184 metal Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- 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
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- 229920003082 Povidone K 90 Polymers 0.000 description 1
- 208000005181 Varicella Zoster Virus Infection Diseases 0.000 description 1
- 208000000260 Warts Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
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- 238000005520 cutting process Methods 0.000 description 1
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- 230000002939 deleterious effect Effects 0.000 description 1
- 229940075894 denatured ethanol Drugs 0.000 description 1
- 150000004683 dihydrates Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
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- 238000005886 esterification reaction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 201000004946 genital herpes Diseases 0.000 description 1
- 239000008202 granule composition Substances 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 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
- 239000007932 molded tablet Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000009702 powder compression Methods 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 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
- 238000000926 separation method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 201000010153 skin papilloma Diseases 0.000 description 1
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- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
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- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000006068 taste-masking agent Substances 0.000 description 1
- 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)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (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)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Saccharide Compounds (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)
| Country | Link |
|---|---|
| US (1) | US6107302A (h) |
| EP (1) | EP0804436B1 (h) |
| JP (1) | JP3176633B2 (h) |
| KR (1) | KR100376074B1 (h) |
| CN (1) | CN1049893C (h) |
| AP (1) | AP662A (h) |
| AR (1) | AR002270A1 (h) |
| AT (1) | ATE302777T1 (h) |
| AU (1) | AU702794B2 (h) |
| BG (1) | BG63393B1 (h) |
| BR (1) | BR9606768A (h) |
| CA (1) | CA2210799C (h) |
| CY (1) | CY2531B1 (h) |
| CZ (1) | CZ297065B6 (h) |
| DE (1) | DE69635106T2 (h) |
| DK (1) | DK0804436T3 (h) |
| EA (1) | EA000364B1 (h) |
| EE (1) | EE03528B1 (h) |
| ES (1) | ES2248806T3 (h) |
| FI (1) | FI973063A7 (h) |
| GB (1) | GB9501178D0 (h) |
| GE (1) | GEP20001940B (h) |
| HR (1) | HRP960024B1 (h) |
| HU (1) | HU222993B1 (h) |
| IL (1) | IL116831A (h) |
| IN (1) | IN182468B (h) |
| IS (1) | IS2268B (h) |
| NO (1) | NO315558B1 (h) |
| NZ (1) | NZ298851A (h) |
| OA (1) | OA10499A (h) |
| PL (1) | PL182175B1 (h) |
| RO (1) | RO118693B1 (h) |
| RS (1) | RS49518B (h) |
| SI (1) | SI0804436T1 (h) |
| SK (1) | SK285329B6 (h) |
| TR (1) | TR199700656T1 (h) |
| UA (1) | UA46001C2 (h) |
| UY (1) | UY25779A1 (h) |
| WO (1) | WO1996022291A1 (h) |
| ZA (1) | ZA96449B (h) |
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 |
| ES2210490T3 (es) * | 1996-01-19 | 2004-07-01 | Glaxo Group Limited | Uso de valaciclovir para la fabricacion de un medicamento para el tratamiento del herpes genital por una unica administracion diaria. |
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| GB9501178D0 (en) * | 1995-01-20 | 1995-03-08 | Wellcome Found | Guanine derivative |
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1995
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Legal Events
| Date | Code | Title | Description |
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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 |