NO315558B1 - Vannfri krystallinsk form av valaciclovir-hydroklorid - Google Patents
Vannfri krystallinsk form av valaciclovir-hydroklorid Download PDFInfo
- Publication number
- NO315558B1 NO315558B1 NO19973326A NO973326A NO315558B1 NO 315558 B1 NO315558 B1 NO 315558B1 NO 19973326 A NO19973326 A NO 19973326A NO 973326 A NO973326 A NO 973326A NO 315558 B1 NO315558 B1 NO 315558B1
- Authority
- NO
- Norway
- Prior art keywords
- hydrochloride
- valaciclovir hydrochloride
- valaciclovir
- weight
- crystalline form
- 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 94
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 56
- 238000000034 method Methods 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 239000000843 powder Substances 0.000 claims description 15
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 14
- 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 13
- 239000013078 crystal Substances 0.000 claims description 13
- 238000009472 formulation Methods 0.000 claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000004615 ingredient Substances 0.000 claims description 12
- 230000003381 solubilizing effect Effects 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 229940093257 valacyclovir Drugs 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000008187 granular material Substances 0.000 claims description 9
- 230000036571 hydration Effects 0.000 claims description 9
- 238000006703 hydration reaction Methods 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- 239000003826 tablet Substances 0.000 claims description 9
- 150000002576 ketones Chemical class 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 239000012458 free base Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 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 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 238000013160 medical therapy Methods 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 150000003839 salts Chemical group 0.000 claims description 5
- 239000007891 compressed tablet Substances 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 3
- 239000002270 dispersing agent Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 239000003701 inert diluent Substances 0.000 claims description 3
- 239000003755 preservative agent Substances 0.000 claims description 3
- 230000002335 preservative effect Effects 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 208000029433 Herpesviridae infectious disease Diseases 0.000 claims description 2
- 239000013557 residual solvent Substances 0.000 claims 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 10
- 239000013543 active substance Substances 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 229960004150 aciclovir Drugs 0.000 description 9
- 239000011928 denatured alcohol Substances 0.000 description 9
- -1 L-valine ester Chemical class 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000002441 X-ray diffraction Methods 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000007788 liquid Substances 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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-Valine Natural products CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 5
- 230000000840 anti-viral effect Effects 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- CANZBRDGRHNSGZ-NSHDSACASA-N (2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 CANZBRDGRHNSGZ-NSHDSACASA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229960004295 valine Drugs 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000011521 glass Substances 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
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 208000007514 Herpes zoster Diseases 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 2
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 2
- 241000701027 Human herpesvirus 6 Species 0.000 description 2
- 241000124008 Mammalia Species 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
- 239000002585 base Substances 0.000 description 2
- 238000009835 boiling Methods 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
- 239000012141 concentrate Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000011812 mixed powder Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-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
- 208000001688 Herpes Genitalis Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 206010019973 Herpes virus infection Diseases 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
- 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 1
- 229920000168 Microcrystalline cellulose Polymers 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
- 208000005181 Varicella Zoster Virus Infection Diseases 0.000 description 1
- 208000036142 Viral 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
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 150000004683 dihydrates Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 201000004946 genital herpes Diseases 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
- 239000006187 pill Substances 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
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 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
- 230000005855 radiation Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000006722 reduction reaction Methods 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
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006068 taste-masking agent Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-M valinate Chemical compound CC(C)C(N)C([O-])=O KZSNJWFQEVHDMF-UHFFFAOYSA-M 0.000 description 1
- 208000010531 varicella zoster infection Diseases 0.000 description 1
- 239000007762 w/o emulsion Substances 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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (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)
- 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 (3)
| Publication Number | Publication Date |
|---|---|
| NO973326D0 NO973326D0 (no) | 1997-07-18 |
| NO973326L NO973326L (no) | 1997-09-16 |
| NO315558B1 true NO315558B1 (no) | 2003-09-22 |
Family
ID=10768347
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19973326A NO315558B1 (no) | 1995-01-20 | 1997-07-18 | Vannfri krystallinsk form av valaciclovir-hydroklorid |
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 |
| DK0874631T3 (da) * | 1996-01-19 | 2004-03-22 | Glaxo Group Ltd | Anvendelse af valaciclovir til fremstilling af et medikament til behandling af genital herpes ved en enkelt daglig anvendelse |
| IT1283447B1 (it) * | 1996-07-18 | 1998-04-21 | Ind Chimica Srl | Processo di preparazione del valaciclovir e relativi intermedi |
| WO1998031683A1 (en) * | 1997-01-17 | 1998-07-23 | Ajinomoto Co., Inc. | Novel z-valacyclovir crystals |
| GB0010446D0 (en) * | 2000-04-28 | 2000-06-14 | Glaxo Wellcome Kk | Pharmaceutical formulation |
| HRPK20110926B3 (hr) * | 2001-02-24 | 2013-05-31 | Boehringer Ingelheim Pharma Gmbh & Co.Kg. | Derivati ksantina, njihova proizvodnja i upotreba kao lijekova |
| US6849736B2 (en) * | 2001-09-07 | 2005-02-01 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of valacyclovir hydrochloride |
| US20040197396A1 (en) * | 2001-11-05 | 2004-10-07 | Fain Helen S | Anhydrous crystal form of valaciclovir hydrochloride |
| KR20050044449A (ko) * | 2001-11-14 | 2005-05-12 | 테바 파마슈티컬 인더스트리즈 리미티드 | 발라시클로비르의 합성 및 정제 방법 |
| WO2004000265A2 (en) * | 2002-06-24 | 2003-12-31 | 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 |
| WO2004035583A1 (en) * | 2002-10-16 | 2004-04-29 | Teva Pharmaceutical Industries Ltd. | Method for reducing residual alcohols in crystalline valacyclovir hydrochloride |
| CA2548608A1 (en) * | 2002-12-09 | 2004-06-24 | Texcontor Etablissement | Anhydrous crystalline form of valacyclovir hydrochloride |
| WO2004106338A1 (en) * | 2003-05-30 | 2004-12-09 | Eos Eczacibasi Ozgun Kimyasal Urunler Sanayi Ve Ticaret A.S. | Novel crystalline forms of valacyclovir hydrochloride |
| US20050085491A1 (en) * | 2003-06-02 | 2005-04-21 | Igor Lifshitz | Novel crystalline forms of valacyclovir hydrochloride |
| TW200536854A (en) * | 2004-01-21 | 2005-11-16 | Teva Pharma | Process for the preparation of valacyclovir hydrochloride |
| US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
| JP2008504255A (ja) * | 2004-06-30 | 2008-02-14 | テバ ファーマシューティカル インダストリーズ リミティド | 結晶塩酸バラシクロビル中の残留アルコールを低減する方法 |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| US20060178512A1 (en) * | 2005-02-04 | 2006-08-10 | Cheruthur Govindan | Method for preparing amino acid esters of nucleoside analogues |
| EP1891071B1 (en) * | 2005-05-25 | 2012-02-22 | Eli Lilly And Company | Cyclopropanecarboxylate esters of acyclovir |
| EP1746098A1 (en) | 2005-07-21 | 2007-01-24 | SOLMAG S.p.A. | Valacyclovir polymorphs and a process for the preparation thereof |
| DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| US20070112193A1 (en) * | 2005-11-14 | 2007-05-17 | Khunt Mayur D | Valacyclovir process |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
| PE20080251A1 (es) * | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| MX2008014024A (es) * | 2006-05-04 | 2008-11-14 | Boehringer Ingelheim Int | Formas poliformas. |
| CN1903854B (zh) * | 2006-08-09 | 2012-05-23 | 丽珠医药集团股份有限公司 | 一种合成盐酸伐昔洛韦的方法 |
| US20080167325A1 (en) * | 2006-12-27 | 2008-07-10 | Bs Praveen Kumar | Valacyclovir compositions |
| US20080281099A1 (en) * | 2007-05-07 | 2008-11-13 | Mayur Devjibhai Khunt | Process for purifying valacyclovir hydrochloride and intermediates thereof |
| GB0710277D0 (en) * | 2007-05-30 | 2007-07-11 | Univ Birmingham | Use of antivirals in the treatment of medical disorders |
| EP2190434B1 (en) * | 2007-08-17 | 2019-04-17 | Boehringer Ingelheim International GmbH | Purin derivatives for use in the treatment of fap-related diseases |
| WO2009031576A1 (ja) * | 2007-09-03 | 2009-03-12 | Ajinomoto Co., Inc. | バラシクロビル塩酸塩結晶の製造方法 |
| US20090076039A1 (en) * | 2007-09-14 | 2009-03-19 | Protia, Llc | Deuterium-enriched valacyclovir |
| PE20091730A1 (es) | 2008-04-03 | 2009-12-10 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
| PE20100156A1 (es) * | 2008-06-03 | 2010-02-23 | Boehringer Ingelheim Int | Tratamiento de nafld |
| BRPI0916997A2 (pt) | 2008-08-06 | 2020-12-15 | Boehringer Ingelheim International Gmbh | Inibidor de dpp-4 e seu uso |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| KR101657960B1 (ko) * | 2008-08-15 | 2016-09-20 | 베링거 인겔하임 인터내셔날 게엠베하 | Ｆａｂ-관련 질환의 치료에 사용하기 위한 푸린 유도체 |
| AU2009290911A1 (en) | 2008-09-10 | 2010-03-18 | Boehringer Ingelheim International Gmbh | Combination therapy for the treatment of diabetes and related conditions |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
| MX2011006713A (es) | 2008-12-23 | 2011-07-13 | Boehringer Ingelheim Int | Formas salinas de compuesto organico. |
| AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
| EP2504002B1 (en) | 2009-11-27 | 2019-10-09 | Boehringer Ingelheim International GmbH | Treatment of genotyped diabetic patients with dpp-iv inhibitors such as linagliptin |
| PH12012502162A1 (en) | 2010-05-05 | 2013-02-04 | Boehringer Ingelheim Int | Combination therapy |
| WO2011158252A1 (en) | 2010-06-15 | 2011-12-22 | Matrix Laboratories Ltd | Process for the preparation of valacyclovir hydrochloride polymorphic form ii |
| KR102018038B1 (ko) | 2010-06-24 | 2019-09-05 | 베링거 인겔하임 인터내셔날 게엠베하 | 당뇨병 요법 |
| US9034883B2 (en) | 2010-11-15 | 2015-05-19 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
| CN102584825B (zh) * | 2011-01-17 | 2014-04-02 | 四川科伦药物研究有限公司 | 一种合成盐酸伐昔洛韦的方法 |
| PL2731947T3 (pl) | 2011-07-15 | 2019-07-31 | Boehringer Ingelheim International Gmbh | Podstawiona dimeryczna pochodna chinazoliny, sposób jej wytwarzania i jej zastosowanie w kompozycjach farmaceutycznych do leczenia cukrzycy typu I i II |
| EP2852592A4 (en) * | 2011-11-25 | 2015-12-23 | Piramal Entpr Ltd | PROCESS FOR THE PREPARATION OF VALACYCLOVIR CHLORHYDRATE |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| WO2013171166A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp-4 inhibitor for use in the treatment of sirs and/or sepsis |
| JP6224084B2 (ja) | 2012-05-14 | 2017-11-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 糸球体上皮細胞関連障害及び／又はネフローゼ症候群の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体 |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
| US9526728B2 (en) | 2014-02-28 | 2016-12-27 | Boehringer Ingelheim International Gmbh | Medical use of a DPP-4 inhibitor |
| BR112018072401A2 (pt) | 2016-06-10 | 2019-02-19 | Boehringer Ingelheim International Gmbh | combinações de linagliptina e metformina |
| CN110437231B (zh) * | 2019-09-04 | 2022-04-29 | 上药康丽（常州）药业有限公司 | 一种盐酸伐昔洛韦无水晶型ⅰ的制备方法 |
| US20230218644A1 (en) | 2020-04-16 | 2023-07-13 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AP160A (en) * | 1987-08-15 | 1991-11-18 | The Wellcome Foundation Ltd | Therapeutic acyclic nucleosides. |
| EP0702682B1 (en) * | 1993-06-10 | 2001-03-14 | Rolabo Sl | Process for the preparation of amino acid esters of nucleoside analogues |
| GB9501178D0 (en) * | 1995-01-20 | 1995-03-08 | Wellcome Found | Guanine derivative |
-
1995
- 1995-01-20 GB GBGB9501178.9A patent/GB9501178D0/en active Pending
-
1996
- 1996-01-19 HR HR960024A patent/HRP960024B1/xx not_active IP Right Cessation
- 1996-01-19 CZ CZ0229497A patent/CZ297065B6/cs not_active IP Right Cessation
- 1996-01-19 DK DK96900631T patent/DK0804436T3/da active
- 1996-01-19 FI FI973063A patent/FI973063A7/fi not_active Application Discontinuation
- 1996-01-19 UA UA97084268A patent/UA46001C2/uk unknown
- 1996-01-19 SI SI9630717T patent/SI0804436T1/sl unknown
- 1996-01-19 EP EP96900631A patent/EP0804436B1/en not_active Expired - Lifetime
- 1996-01-19 PL PL96321326A patent/PL182175B1/pl not_active IP Right Cessation
- 1996-01-19 EE EE9700175A patent/EE03528B1/xx not_active IP Right Cessation
- 1996-01-19 RO RO97-01334A patent/RO118693B1/ro unknown
- 1996-01-19 AT AT96900631T patent/ATE302777T1/de not_active IP Right Cessation
- 1996-01-19 ES ES96900631T patent/ES2248806T3/es not_active Expired - Lifetime
- 1996-01-19 EA EA199700124A patent/EA000364B1/ru not_active IP Right Cessation
- 1996-01-19 AU AU44539/96A patent/AU702794B2/en not_active Ceased
- 1996-01-19 NZ NZ298851A patent/NZ298851A/xx not_active IP Right Cessation
- 1996-01-19 WO PCT/GB1996/000117 patent/WO1996022291A1/en not_active Ceased
- 1996-01-19 IL IL11683196A patent/IL116831A/en not_active IP Right Cessation
- 1996-01-19 ZA ZA96449A patent/ZA96449B/xx unknown
- 1996-01-19 GE GEAP19963845A patent/GEP20001940B/en unknown
- 1996-01-19 TR TR97/00656T patent/TR199700656T1/xx unknown
- 1996-01-19 CA CA002210799A patent/CA2210799C/en not_active Expired - Fee Related
- 1996-01-19 JP JP52213196A patent/JP3176633B2/ja not_active Expired - Fee Related
- 1996-01-19 IN IN102MA1996 patent/IN182468B/en unknown
- 1996-01-19 DE DE69635106T patent/DE69635106T2/de not_active Expired - Lifetime
- 1996-01-19 AP APAP/P/1997/001058A patent/AP662A/en active
- 1996-01-19 BR BR9606768A patent/BR9606768A/pt active IP Right Grant
- 1996-01-19 KR KR1019970704916A patent/KR100376074B1/ko not_active Expired - Lifetime
- 1996-01-19 CN CN96192662A patent/CN1049893C/zh not_active Expired - Fee Related
- 1996-01-19 HU HU9801836A patent/HU222993B1/hu not_active IP Right Cessation
- 1996-01-19 AR ARP960101082A patent/AR002270A1/es not_active Application Discontinuation
- 1996-01-19 RS YU3396A patent/RS49518B/sr unknown
- 1996-01-19 US US08/875,173 patent/US6107302A/en not_active Expired - Lifetime
- 1996-01-19 SK SK965-97A patent/SK285329B6/sk not_active IP Right Cessation
-
1997
- 1997-07-15 IS IS4527A patent/IS2268B/is unknown
- 1997-07-16 OA OA70051A patent/OA10499A/en unknown
- 1997-07-18 NO NO19973326A patent/NO315558B1/no not_active IP Right Cessation
- 1997-08-14 BG BG101833A patent/BG63393B1/bg unknown
-
1999
- 1999-10-29 UY UY25779A patent/UY25779A1/es not_active IP Right Cessation
-
2005
- 2005-11-16 CY CY0500061A patent/CY2531B1/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO315558B1 (no) | Vannfri krystallinsk form av valaciclovir-hydroklorid | |
| KR100412298B1 (ko) | 콜로이드이산화규소를함유하는발라시클로비르정제 | |
| CA2243237C (en) | Use of valaciclovir for the manufacture of a medicament for the treatment of genital herpes by a single daily application | |
| EP3749673B1 (en) | Crystalline form of bictegravir sodium | |
| MXPA97005462A (en) | Derived from guan | |
| EA020944B1 (ru) | Кристаллическая форма i соли розувастатина цинка | |
| HK1003055B (en) | Guanine derivative | |
| HK1063621B (en) | Crystalline form of a phenylethanolamine, the preparation thereof and pharmaceutical compositions comprising the same | |
| MXPA97005459A (en) | Valaciclovir tablets containing silicon dioxide color | |
| HK1063621A1 (zh) | 苯基乙醇胺的晶形，其製備方法和含有它的藥物組合物 | |
| CZ20003709A3 (cs) | Nové krystalické formy protivirivé benzimidazolové sloučeniny |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |