JP2018508559A5 - - Google Patents

Info

Publication number

JP2018508559A5

JP2018508559A5 JP2017549232A JP2017549232A JP2018508559A5 JP 2018508559 A5 JP2018508559 A5 JP 2018508559A5 JP 2017549232 A JP2017549232 A JP 2017549232A JP 2017549232 A JP2017549232 A JP 2017549232A JP 2018508559 A5 JP2018508559 A5 JP 2018508559A5

Authority

JP

Japan

Prior art keywords

pharmaceutical composition

item

fumarate

acid ester

fumaric acid

Prior art date

2016-03-18

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Withdrawn

Links

• Espacenet
• Global Dossier
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• 238000000034 method Methods 0.000 claims description 246
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 182
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 175
• 239000008194 pharmaceutical composition Substances 0.000 claims description 175
• LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical group COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 claims description 112
• 229960004419 dimethyl fumarate Drugs 0.000 claims description 112
• -1 fumaric acid ester Chemical class 0.000 claims description 91
• 239000001530 fumaric acid Substances 0.000 claims description 82
• 238000001990 intravenous administration Methods 0.000 claims description 65
• 239000013543 active substance Substances 0.000 claims description 47
• 229920000858 Cyclodextrin Polymers 0.000 claims description 42
• 239000007864 aqueous solution Substances 0.000 claims description 22
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 22
• 229960004853 betadex Drugs 0.000 claims description 22
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 22
• 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 20
• 239000001116 FEMA 4028 Substances 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 claims description 16
• 201000006417 multiple sclerosis Diseases 0.000 claims description 12
• 229920001450 Alpha-Cyclodextrin Polymers 0.000 claims description 10
• HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 claims description 10
• 229940043377 alpha-cyclodextrin Drugs 0.000 claims description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 9
• 239000006070 nanosuspension Substances 0.000 claims description 9
• 239000003381 stabilizer Substances 0.000 claims description 9
• 206010020751 Hypersensitivity Diseases 0.000 claims description 8
• 208000026935 allergic disease Diseases 0.000 claims description 8
• 239000003795 chemical substances by application Substances 0.000 claims description 8
• 150000001875 compounds Chemical class 0.000 claims description 8
• NKHAVTQWNUWKEO-UHFFFAOYSA-N fumaric acid monomethyl ester Natural products COC(=O)C=CC(O)=O NKHAVTQWNUWKEO-UHFFFAOYSA-N 0.000 claims description 8
• 230000009610 hypersensitivity Effects 0.000 claims description 8
• 210000000987 immune system Anatomy 0.000 claims description 8
• 239000002955 immunomodulating agent Substances 0.000 claims description 8
• 229940121354 immunomodulator Drugs 0.000 claims description 8
• 230000002584 immunomodulator Effects 0.000 claims description 8
• 229960003444 immunosuppressant agent Drugs 0.000 claims description 8
• 230000001861 immunosuppressant effect Effects 0.000 claims description 8
• 239000003018 immunosuppressive agent Substances 0.000 claims description 8
• 239000000644 isotonic solution Substances 0.000 claims description 8
• NKHAVTQWNUWKEO-NSCUHMNNSA-N monomethyl fumarate Chemical compound COC(=O)\C=C\C(O)=O NKHAVTQWNUWKEO-NSCUHMNNSA-N 0.000 claims description 8
• 229940005650 monomethyl fumarate Drugs 0.000 claims description 8
• 229960005027 natalizumab Drugs 0.000 claims description 8
• 208000007118 chronic progressive multiple sclerosis Diseases 0.000 claims description 7
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 6
• 239000000872 buffer Substances 0.000 claims description 5
• 239000000203 mixture Substances 0.000 claims description 5
• 229940002612 prodrug Drugs 0.000 claims description 5
• 239000000651 prodrug Substances 0.000 claims description 5
• 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 claims description 5
• 208000012902 Nervous system disease Diseases 0.000 claims description 4
• 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims description 4
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
• 238000000354 decomposition reaction Methods 0.000 claims description 4
• 239000008363 phosphate buffer Substances 0.000 claims description 4
• 201000008628 secondary progressive multiple sclerosis Diseases 0.000 claims description 4
• 150000003384 small molecules Chemical class 0.000 claims description 4
• 239000011734 sodium Substances 0.000 claims description 4
• 206010053395 Progressive multiple sclerosis Diseases 0.000 claims description 3
• 206010063401 primary progressive multiple sclerosis Diseases 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 2
• 208000023105 Huntington disease Diseases 0.000 claims description 2
• 208000018737 Parkinson disease Diseases 0.000 claims description 2
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
• 239000002245 particle Substances 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 2
• 208000006011 Stroke Diseases 0.000 claims 2
• 208000016988 Hemorrhagic Stroke Diseases 0.000 claims 1
• 208000032382 Ischaemic stroke Diseases 0.000 claims 1
• 230000002354 daily effect Effects 0.000 claims 1
• 229940079593 drug Drugs 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 230000003203 everyday effect Effects 0.000 claims 1
• 208000020658 intracerebral hemorrhage Diseases 0.000 claims 1
• 150000002148 esters Chemical class 0.000 description 7
• 238000011285 therapeutic regimen Methods 0.000 description 7
• 230000015556 catabolic process Effects 0.000 description 4
• 238000006731 degradation reaction Methods 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1