NO321267B1 - Polymorfe av donepezilhydroklorid, fremgangsmater for fremstilling derav, anvendelse derav samt terapeutisk preparat inneholdende den samme. - Google Patents
Polymorfe av donepezilhydroklorid, fremgangsmater for fremstilling derav, anvendelse derav samt terapeutisk preparat inneholdende den samme. Download PDFInfo
- Publication number
- NO321267B1 NO321267B1 NO19985721A NO985721A NO321267B1 NO 321267 B1 NO321267 B1 NO 321267B1 NO 19985721 A NO19985721 A NO 19985721A NO 985721 A NO985721 A NO 985721A NO 321267 B1 NO321267 B1 NO 321267B1
- Authority
- NO
- Norway
- Prior art keywords
- polymorph
- donepezil hydrochloride
- donepezil
- iii
- stated
- Prior art date
Links
- 229960003135 donepezil hydrochloride Drugs 0.000 title claims abstract description 222
- XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 title claims abstract description 222
- 238000000034 method Methods 0.000 title claims description 86
- 230000008569 process Effects 0.000 title claims description 25
- 238000002360 preparation method Methods 0.000 title claims description 16
- 230000001225 therapeutic effect Effects 0.000 title claims description 3
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims abstract description 70
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 33
- 238000000862 absorption spectrum Methods 0.000 claims abstract description 24
- 238000010521 absorption reaction Methods 0.000 claims abstract description 19
- QDUXDCXILAPLAG-UHFFFAOYSA-N hydron;1-methylpiperidine;chloride Chemical compound Cl.CN1CCCCC1 QDUXDCXILAPLAG-UHFFFAOYSA-N 0.000 claims abstract 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 204
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 185
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 178
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 129
- 239000013078 crystal Substances 0.000 claims description 95
- 229960003530 donepezil Drugs 0.000 claims description 89
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 78
- 239000000203 mixture Substances 0.000 claims description 69
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 63
- 238000010438 heat treatment Methods 0.000 claims description 58
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 46
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 34
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 33
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 32
- 238000004519 manufacturing process Methods 0.000 claims description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- 206010039966 Senile dementia Diseases 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 6
- 230000008025 crystallization Effects 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 102000012440 Acetylcholinesterase Human genes 0.000 claims description 4
- 108010022752 Acetylcholinesterase Proteins 0.000 claims description 4
- 229940022698 acetylcholinesterase Drugs 0.000 claims description 4
- 238000002441 X-ray diffraction Methods 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 239000012456 homogeneous solution Substances 0.000 claims 1
- 238000001556 precipitation Methods 0.000 claims 1
- IHMQOBPGHZFGLC-UHFFFAOYSA-N 5,6-dimethoxy-2,3-dihydroinden-1-one Chemical compound C1=C(OC)C(OC)=CC2=C1C(=O)CC2 IHMQOBPGHZFGLC-UHFFFAOYSA-N 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 95
- 238000001914 filtration Methods 0.000 description 85
- 238000001035 drying Methods 0.000 description 76
- 239000005457 ice water Substances 0.000 description 76
- 238000003756 stirring Methods 0.000 description 53
- 239000000243 solution Substances 0.000 description 52
- 238000004090 dissolution Methods 0.000 description 31
- 238000010992 reflux Methods 0.000 description 16
- 238000001816 cooling Methods 0.000 description 15
- 238000002411 thermogravimetry Methods 0.000 description 13
- 238000000926 separation method Methods 0.000 description 12
- 238000002076 thermal analysis method Methods 0.000 description 11
- 238000005342 ion exchange Methods 0.000 description 8
- 239000008213 purified water Substances 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 7
- 238000003860 storage Methods 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000000356 contaminant Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000009423 ventilation Methods 0.000 description 5
- -1 1-benzyl-4-[(5 Chemical compound 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000000691 measurement method Methods 0.000 description 3
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012907 medicinal substance Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000006190 sub-lingual tablet Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000004861 thermometry Methods 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- 206010050013 Abulia Diseases 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- 101000878595 Arabidopsis thaliana Squalene synthase 1 Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229960001777 castor oil Drugs 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 206010008129 cerebral palsy Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 229940013361 cresol Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000004455 differential thermal analysis Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 201000005851 intracranial arteriosclerosis Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 208000027765 speech disease Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14629396 | 1996-06-07 | ||
| PCT/JP1996/003881 WO1997046526A1 (fr) | 1996-06-07 | 1996-12-27 | Polymorphes stables d'hydrochlorure de 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methyl-piperidine), dit hydrochlorure de donepezil et procede pour leur production |
| US08/774,802 US6140321A (en) | 1996-06-07 | 1996-12-30 | Polymorphs of donepezil hydrochloride and process for production |
| PCT/JP1997/001932 WO1997046527A1 (fr) | 1996-06-07 | 1997-06-06 | Polymorphes de chlorhydrate de donepezil, et leur procede de production |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO985721D0 NO985721D0 (no) | 1998-12-07 |
| NO985721L NO985721L (no) | 1999-01-28 |
| NO321267B1 true NO321267B1 (no) | 2006-04-10 |
Family
ID=27307991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19985721A NO321267B1 (no) | 1996-06-07 | 1998-12-07 | Polymorfe av donepezilhydroklorid, fremgangsmater for fremstilling derav, anvendelse derav samt terapeutisk preparat inneholdende den samme. |
Country Status (12)
| Country | Link |
|---|---|
| EP (2) | EP1019374B1 (fr) |
| AU (1) | AU731282B2 (fr) |
| CA (1) | CA2252806C (fr) |
| DK (1) | DK1019374T3 (fr) |
| ES (1) | ES2188946T3 (fr) |
| HK (1) | HK1020952A1 (fr) |
| NO (1) | NO321267B1 (fr) |
| NZ (1) | NZ333197A (fr) |
| RU (1) | RU2190603C2 (fr) |
| SI (1) | SI9720038B (fr) |
| SK (1) | SK285312B6 (fr) |
| WO (1) | WO1997046527A1 (fr) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE241358T1 (de) | 1997-03-03 | 2003-06-15 | Eisai Co Ltd | Verwendung von cholinesterasehemmer zur behandlung von konzentrationsstörungen |
| GB9716879D0 (en) * | 1997-08-08 | 1997-10-15 | Shire Int Licensing Bv | Treatment of attention deficit disorders |
| ATE260896T1 (de) | 1997-12-05 | 2004-03-15 | Eisai Co Ltd | Donepezil polykristalle und verfharen zu ihrer herstellung |
| US6193993B1 (en) * | 1998-03-03 | 2001-02-27 | Eisai Co., Ltd. | Suppository containing an antidementia medicament |
| PL346242A1 (en) * | 1998-06-16 | 2002-01-28 | Lilly Co Eli | Methods for increasing levels of acetylcholine |
| TR200003704T2 (tr) | 1998-06-16 | 2001-06-21 | Eli Lilly And Company | Asetilkolin düzeylerini arttırma |
| US6288108B1 (en) | 1998-06-16 | 2001-09-11 | Eli Lilly And Company | Methods for increasing levels of acetylcholine |
| PT1311272E (pt) | 2000-03-03 | 2007-02-28 | Eisai R&D Man Co Ltd | Novos métodos utilizando inibidores de colinesterase |
| SI21223A (sl) * | 2002-06-19 | 2003-12-31 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Farmacevtska formulacija s stabiliziranim amorfnim donepezilijevim kloridom |
| IL150509A (en) | 2002-07-01 | 2007-07-04 | Joseph Kaspi | Pharmaceutical preparations containing donafazil hydrochloride |
| AU2003287433A1 (en) * | 2002-11-01 | 2004-06-07 | Oregon Health And Science University | Treatment of hyperkinetic movement disorder with donepezil |
| US7186842B2 (en) | 2003-02-12 | 2007-03-06 | Usv, Ltd. | Polymorph of (1-benzyl-4-[(5,6-dimethoxy-1-indanone)-2-y1] methyl piperidine hydrochloride (Donepezil hydrochloride) and a process for producing thereof |
| US20050288330A1 (en) * | 2004-06-29 | 2005-12-29 | Avinash Naidu | Process for producing a polymorphic form of (1-Benzyl-4-[(5,6-dimethoxy-1-indanone)-2-yl] methyl piperidine hydrochloride (donepezil hydrochloride) |
| WO2004092137A1 (fr) * | 2003-04-16 | 2004-10-28 | Hetero Drugs Limited | Nouvelles formes cristallines de chlorhydrate de donepezil |
| EP1771416A1 (fr) * | 2004-07-28 | 2007-04-11 | USV Limited | Nouveau polymorphe de (1-benzyl-4-[(5,6-dimethoxy-1-indanone)-2-yl] methyl piperidine hydrochlorure (hydrochlorure de donepezil) et son procede de production |
| WO2006015338A2 (fr) * | 2004-07-30 | 2006-02-09 | Dr. Reddy's Laboratories Ltd. | Forme cristalline de chlorhydrate de donepezil |
| RS51271B (sr) * | 2004-10-19 | 2010-12-31 | Krka Tovarna Zdravil D.D. | Čvrsta farmaceutska kompozicija koja sadrži donepezil hidrohlorid |
| EP1858847A1 (fr) * | 2005-02-28 | 2007-11-28 | Ranbaxy Laboratories Limited | Chlorhydrate de donepezil de formule i stable et son procede de preparation et d'utilisation dans des compositions pharmaceutiques |
| WO2006097341A1 (fr) * | 2005-03-17 | 2006-09-21 | Synthon B.V. | Procede de preparation du monohydrate d'hydrochlorure de donepezil cristallin |
| WO2006111983A2 (fr) * | 2005-04-21 | 2006-10-26 | Jubilant Organosys Limited | Nouvelle forme polymorphe de chlorhydrate de (l-benzyl-4-[(5,6-dimethoxy-l- indanone)-2-yl]methyl piperidine et procede permettant de preparer celle-ci |
| GB0515803D0 (en) * | 2005-07-30 | 2005-09-07 | Pliva Hrvatska D O O | Intermediate compounds |
| HU227474B1 (en) * | 2005-12-20 | 2011-07-28 | Richter Gedeon Nyrt | Process for industrial scale production of high purity donepezil hydrochloride polymorph i. |
| SI2032521T1 (sl) | 2006-06-27 | 2010-02-26 | Sandoz Ag | Nov postopek za pripravo soli |
| US8247563B2 (en) | 2006-12-11 | 2012-08-21 | Reviva Pharmaceuticals, Inc. | Compositions, synthesis, and methods of using indanone based cholinesterase inhibitors |
| DE102007037932A1 (de) | 2007-08-11 | 2009-02-12 | Alfred E. Tiefenbacher Gmbh & Co.Kg | Donepezilhydrochlorid in amorpher Form enthaltende Tablette |
| CN102603612A (zh) * | 2007-09-28 | 2012-07-25 | 天津和美生物技术有限公司 | 多奈哌齐盐的多晶型物及其制备和应用 |
| JP5562337B2 (ja) * | 2008-12-17 | 2014-07-30 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ドネペジルの多形結晶及びその製造方法 |
| DE102010010998A1 (de) | 2010-03-10 | 2011-09-15 | Stada Arzneimittel Ag | Feste pharmazeutische Zusammensetzung, umfassend Donepezil-Hydrochlorid der kristallinen polymorphen Form I |
| WO2011151359A1 (fr) | 2010-06-02 | 2011-12-08 | Noscira, S.A. | Traitement combiné comprenant un inhibiteur de la cholinestérase et un dérivé de thiadiazolidinedione |
| EP2502620A1 (fr) | 2011-03-24 | 2012-09-26 | Krka Tovarna Zdravil, D.D., Novo Mesto | Composition pharmaceutique solide comportant du donépézil |
| CN110393440B (zh) * | 2019-06-28 | 2021-08-13 | 顾美红 | 一种即热式烧水机 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI95572C (fi) * | 1987-06-22 | 1996-02-26 | Eisai Co Ltd | Menetelmä lääkeaineena käyttökelpoisen piperidiinijohdannaisten tai sen farmaseuttisen suolan valmistamiseksi |
-
1997
- 1997-06-06 CA CA002252806A patent/CA2252806C/fr not_active Expired - Lifetime
- 1997-06-06 RU RU99100325/04A patent/RU2190603C2/ru active
- 1997-06-06 ES ES97924337T patent/ES2188946T3/es not_active Expired - Lifetime
- 1997-06-06 EP EP97924337A patent/EP1019374B1/fr not_active Expired - Lifetime
- 1997-06-06 NZ NZ333197A patent/NZ333197A/en not_active IP Right Cessation
- 1997-06-06 SI SI9720038A patent/SI9720038B/sl active Search and Examination
- 1997-06-06 AU AU29792/97A patent/AU731282B2/en not_active Expired
- 1997-06-06 DK DK97924337T patent/DK1019374T3/da active
- 1997-06-06 SK SK1676-98A patent/SK285312B6/sk not_active IP Right Cessation
- 1997-06-06 EP EP02005248A patent/EP1211243B1/fr not_active Expired - Lifetime
- 1997-06-06 WO PCT/JP1997/001932 patent/WO1997046527A1/fr not_active Application Discontinuation
-
1998
- 1998-12-07 NO NO19985721A patent/NO321267B1/no not_active IP Right Cessation
-
1999
- 1999-12-24 HK HK99106107A patent/HK1020952A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SI9720038A (sl) | 1999-06-30 |
| NO985721L (no) | 1999-01-28 |
| SI9720038B (sl) | 2010-06-30 |
| NO985721D0 (no) | 1998-12-07 |
| SK167698A3 (en) | 1999-06-11 |
| EP1211243B1 (fr) | 2009-10-14 |
| SK285312B6 (sk) | 2006-10-05 |
| EP1211243A1 (fr) | 2002-06-05 |
| HK1020952A1 (en) | 2000-05-26 |
| WO1997046527A1 (fr) | 1997-12-11 |
| DK1019374T3 (da) | 2003-04-07 |
| RU2190603C2 (ru) | 2002-10-10 |
| ES2188946T3 (es) | 2003-07-01 |
| EP1019374B1 (fr) | 2003-01-02 |
| AU731282B2 (en) | 2001-03-29 |
| CA2252806A1 (fr) | 1997-12-11 |
| NZ333197A (en) | 2001-03-30 |
| CA2252806C (fr) | 2005-11-22 |
| AU2979297A (en) | 1998-01-05 |
| EP1019374A1 (fr) | 2000-07-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO321267B1 (no) | Polymorfe av donepezilhydroklorid, fremgangsmater for fremstilling derav, anvendelse derav samt terapeutisk preparat inneholdende den samme. | |
| CA2516108C (fr) | Polymorphes du chlorhydrate de donepezil et procede pour leur production | |
| US5985864A (en) | Polymorphs of donepezil hydrochloride and process for production | |
| EP1048653B1 (fr) | Polycristaux de donepezil et leur procede de production | |
| NO341039B1 (no) | Farmasøytisk sammensetning omfattende en polymorf form av 3-(4-amino-1-okso-1,3 dihydro-isoindol-2-yl)-piperidin-1,6-dion | |
| JPH10500134A (ja) | 抗ヒスタミン性ピペリジン誘導体の無水および水和形態、それらの多形態および擬似形態の製造方法 | |
| KR20160003899A (ko) | 마크롤리드 고체상 형태 | |
| NO155490B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktivt 4-)1"-hydroksy-2"-(n-imidazolyl)etyl)bibenzyl. | |
| JPH1053576A (ja) | 塩酸ドネペジルの多形結晶およびその製造法 | |
| RO121382B1 (ro) | Procedeu şi intermediari pentru prepararea 1-benzil-4-[(5,6-dimetoxi-1-indanon)-2-il-]metilpiperidinei | |
| ITMI20011726A1 (it) | Forme polimorfe della lercanidipina cloridrato | |
| TWI537270B (zh) | Ｇｒａｐｉｐｒａｎｔ之結晶型式 | |
| EA019689B1 (ru) | Бензолсульфонат 2-[[[2-[(гидроксиацетил)амино]-4-пиридинил]метил]тио]-n-[4-(трифторметокси)фенил]-3-пиридинкарбоксамида, его кристаллы, его полиморфы и способы их получения | |
| JPH0660160B2 (ja) | アミド誘導体およびこれを含有する抗アレルギ−剤 | |
| WO2003011295A1 (fr) | Agent polymorphe de fexofenadine | |
| TWI243816B (en) | Polymorphs of donepezil hydrochloride and process for production | |
| JP2005502648A (ja) | 塩酸レルカニジピンの溶媒和物及び塩酸レルカニジピンの新しい結晶性形状 | |
| AU592498B2 (en) | Dihydropyridines | |
| JPH06166686A (ja) | 新規ベンゾピラン化合物、それらの製造方法およびこれらの化合物を含有する医薬組成物 | |
| WO2023153422A1 (fr) | Forme cristalline de composé cyclohexénone | |
| KR100522574B1 (ko) | 염산도네페질의다형결정및그제법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |