JP2019059732A - フマル酸ジメチルを含有する医薬組成物 - Google Patents
フマル酸ジメチルを含有する医薬組成物 Download PDFInfo
- Publication number
- JP2019059732A JP2019059732A JP2018204599A JP2018204599A JP2019059732A JP 2019059732 A JP2019059732 A JP 2019059732A JP 2018204599 A JP2018204599 A JP 2018204599A JP 2018204599 A JP2018204599 A JP 2018204599A JP 2019059732 A JP2019059732 A JP 2019059732A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- alkyl
- substituted
- dmf
- formula
- Prior art date
- 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.)
- Pending
Links
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 title claims abstract description 191
- 229960004419 dimethyl fumarate Drugs 0.000 title claims abstract description 191
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 176
- -1 hydroxyl propyl Chemical group 0.000 claims abstract description 71
- 238000000034 method Methods 0.000 claims abstract description 39
- 229920001577 copolymer Polymers 0.000 claims abstract description 27
- 239000000314 lubricant Substances 0.000 claims abstract description 26
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 26
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 19
- 239000007884 disintegrant Substances 0.000 claims abstract description 17
- 239000001913 cellulose Substances 0.000 claims abstract description 13
- 229920002678 cellulose Polymers 0.000 claims abstract description 11
- OSNIIMCBVLBNGS-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-2-(dimethylamino)propan-1-one Chemical compound CN(C)C(C)C(=O)C1=CC=C2OCOC2=C1 OSNIIMCBVLBNGS-UHFFFAOYSA-N 0.000 claims abstract description 8
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 6
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 6
- 229920001249 ethyl cellulose Polymers 0.000 claims abstract description 6
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims abstract description 3
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims abstract description 3
- NZEXUPLJXSDMCK-UHFFFAOYSA-N methyl 2-methylprop-2-enoate;methyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound COC(=O)C=C.CC(=C)C(O)=O.COC(=O)C(C)=C NZEXUPLJXSDMCK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 203
- 125000000217 alkyl group Chemical group 0.000 claims description 121
- NKHAVTQWNUWKEO-NSCUHMNNSA-N monomethyl fumarate Chemical compound COC(=O)\C=C\C(O)=O NKHAVTQWNUWKEO-NSCUHMNNSA-N 0.000 claims description 74
- NKHAVTQWNUWKEO-UHFFFAOYSA-N fumaric acid monomethyl ester Natural products COC(=O)C=CC(O)=O NKHAVTQWNUWKEO-UHFFFAOYSA-N 0.000 claims description 71
- 229940005650 monomethyl fumarate Drugs 0.000 claims description 70
- 239000001257 hydrogen Substances 0.000 claims description 67
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- 238000000576 coating method Methods 0.000 claims description 60
- 239000011248 coating agent Substances 0.000 claims description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
- 239000002775 capsule Substances 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 239000002552 dosage form Substances 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 230000006835 compression Effects 0.000 claims description 32
- 238000007906 compression Methods 0.000 claims description 32
- 238000011010 flushing procedure Methods 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 31
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 25
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 239000000843 powder Substances 0.000 claims description 15
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 14
- 239000000454 talc Substances 0.000 claims description 14
- 229910052623 talc Inorganic materials 0.000 claims description 14
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 13
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
- 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 claims description 12
- 239000000377 silicon dioxide Substances 0.000 claims description 12
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 10
- 235000010980 cellulose Nutrition 0.000 claims description 10
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 10
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 10
- 235000019359 magnesium stearate Nutrition 0.000 claims description 10
- 239000002245 particle Substances 0.000 claims description 10
- 239000004606 Fillers/Extenders Substances 0.000 claims description 9
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 9
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 9
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 239000011777 magnesium Substances 0.000 claims description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 7
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 239000001530 fumaric acid Substances 0.000 claims description 6
- 150000002367 halogens Chemical group 0.000 claims description 6
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 5
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- PMVSDNDAUGGCCE-TYYBGVCCSA-L Ferrous fumarate Chemical compound [Fe+2].[O-]C(=O)\C=C\C([O-])=O PMVSDNDAUGGCCE-TYYBGVCCSA-L 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 abstract description 6
- 230000004770 neurodegeneration Effects 0.000 abstract description 4
- 239000000945 filler Substances 0.000 abstract description 2
- 235000002639 sodium chloride Nutrition 0.000 description 30
- 239000002702 enteric coating Substances 0.000 description 27
- 238000009505 enteric coating Methods 0.000 description 27
- 238000011282 treatment Methods 0.000 description 26
- 238000012360 testing method Methods 0.000 description 23
- 208000024891 symptom Diseases 0.000 description 21
- 239000000047 product Substances 0.000 description 20
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 18
- 239000003826 tablet Substances 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 239000004067 bulking agent Substances 0.000 description 14
- 230000002496 gastric effect Effects 0.000 description 14
- 235000012222 talc Nutrition 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 229940068196 placebo Drugs 0.000 description 12
- 239000000902 placebo Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 description 9
- 101000652736 Homo sapiens Transgelin Proteins 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 102100031013 Transgelin Human genes 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 8
- 230000036470 plasma concentration Effects 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 229940033134 talc Drugs 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 239000011230 binding agent Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 239000004014 plasticizer Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 230000017531 blood circulation Effects 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 6
- 239000002207 metabolite Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 0 C[C@@](*)C(C(*)(*)[Cl+]C(C=CC(C*)=C)=C)=C Chemical compound C[C@@](*)C(C(*)(*)[Cl+]C(C=CC(C*)=C)=C)=C 0.000 description 5
- 229920003134 Eudragit® polymer Polymers 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 5
- 238000000748 compression moulding Methods 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 239000006186 oral dosage form Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 229910000077 silane Inorganic materials 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 229940032147 starch Drugs 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- NIQCNGHVCWTJSM-UHFFFAOYSA-N Dimethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(=O)OC NIQCNGHVCWTJSM-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 4
- 230000002485 urinary effect Effects 0.000 description 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 3
- XLYMOEINVGRTEX-ONEGZZNKSA-N (e)-4-ethoxy-4-oxobut-2-enoic acid Chemical class CCOC(=O)\C=C\C(O)=O XLYMOEINVGRTEX-ONEGZZNKSA-N 0.000 description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- XCFSFJDCOYDVQR-KQQUZDAGSA-N 4-o-[[(e)-4-methoxy-4-oxobut-2-enoyl]oxy-dimethylsilyl] 1-o-methyl (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)O[Si](C)(C)OC(=O)\C=C\C(=O)OC XCFSFJDCOYDVQR-KQQUZDAGSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 3
- 235000021355 Stearic acid Nutrition 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 150000004756 silanes Chemical class 0.000 description 3
- 239000011734 sodium Chemical class 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229940083542 sodium Drugs 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
- 239000000661 sodium alginate Substances 0.000 description 3
- 229940005550 sodium alginate Drugs 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 239000001069 triethyl citrate Substances 0.000 description 3
- 235000013769 triethyl citrate Nutrition 0.000 description 3
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 3
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- GXELJHLYETVMRK-SZKDQXIBSA-N (2s)-2-amino-4-[[(e)-4-methoxy-4-oxobut-2-enoyl]oxymethoxy]-4-oxobutanoic acid Chemical compound COC(=O)\C=C\C(=O)OCOC(=O)C[C@H](N)C(O)=O GXELJHLYETVMRK-SZKDQXIBSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
- URJPHBCJYCQTKQ-NSCUHMNNSA-N 1-o-methyl 4-o-(2-morpholin-4-yl-2-oxoethyl) (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OCC(=O)N1CCOCC1 URJPHBCJYCQTKQ-NSCUHMNNSA-N 0.000 description 2
- YNDLGWWCCXRXQP-NSCUHMNNSA-N 1-o-methyl 4-o-(2-oxo-2-piperazin-1-ylethyl) (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OCC(=O)N1CCNCC1 YNDLGWWCCXRXQP-NSCUHMNNSA-N 0.000 description 2
- NUMOPPOEPGJACY-SNAWJCMRSA-N 1-o-methyl 4-o-(2-propan-2-yloxycarbonyloxyethyl) (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OCCOC(=O)OC(C)C NUMOPPOEPGJACY-SNAWJCMRSA-N 0.000 description 2
- JMJLMVYJKPMZOF-NSCUHMNNSA-N 1-o-methyl 4-o-(trihydroxysilylmethyl) (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OC[Si](O)(O)O JMJLMVYJKPMZOF-NSCUHMNNSA-N 0.000 description 2
- JETSOFMWNXQIQA-AATRIKPKSA-N 1-o-methyl 4-o-(trimethoxysilylmethyl) (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OC[Si](OC)(OC)OC JETSOFMWNXQIQA-AATRIKPKSA-N 0.000 description 2
- HXPUJILWUFUJFD-SNAWJCMRSA-N 1-o-methyl 4-o-[2-(2-methylpropanoyloxy)ethyl] (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OCCOC(=O)C(C)C HXPUJILWUFUJFD-SNAWJCMRSA-N 0.000 description 2
- PXGPLTODNUVGFL-ZWAKLXPCSA-N 11-epi-prostaglandin F2alpha Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O PXGPLTODNUVGFL-ZWAKLXPCSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DWYJAVLQLQZVRF-NSCUHMNNSA-N 2-[[2-[(e)-4-methoxy-4-oxobut-2-enoyl]oxyacetyl]amino]acetic acid Chemical compound COC(=O)\C=C\C(=O)OCC(=O)NCC(O)=O DWYJAVLQLQZVRF-NSCUHMNNSA-N 0.000 description 2
- ZHQVNRMCKLTSLS-SNAWJCMRSA-N 4-[[2-[(e)-4-methoxy-4-oxobut-2-enoyl]oxyacetyl]amino]butanoic acid Chemical compound COC(=O)\C=C\C(=O)OCC(=O)NCCCC(O)=O ZHQVNRMCKLTSLS-SNAWJCMRSA-N 0.000 description 2
- QIJLQYHKDKHWOG-BQYQJAHWSA-N 4-o-(2-benzoyloxyethyl) 1-o-methyl (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OCCOC(=O)C1=CC=CC=C1 QIJLQYHKDKHWOG-BQYQJAHWSA-N 0.000 description 2
- ORFHNYKYSVEILP-SNAWJCMRSA-N 4-o-(2-ethoxycarbonyloxyethyl) 1-o-methyl (e)-but-2-enedioate Chemical compound CCOC(=O)OCCOC(=O)\C=C\C(=O)OC ORFHNYKYSVEILP-SNAWJCMRSA-N 0.000 description 2
- DBALCVVDGWTCCO-ONEGZZNKSA-N 4-o-[2-(2-methoxyethylamino)-2-oxoethyl] 1-o-methyl (e)-but-2-enedioate Chemical compound COCCNC(=O)COC(=O)\C=C\C(=O)OC DBALCVVDGWTCCO-ONEGZZNKSA-N 0.000 description 2
- OUPDOPULPSPHAA-AATRIKPKSA-N 4-o-[2-(butylamino)-2-oxoethyl] 1-o-methyl (e)-but-2-enedioate Chemical compound CCCCNC(=O)COC(=O)\C=C\C(=O)OC OUPDOPULPSPHAA-AATRIKPKSA-N 0.000 description 2
- AKUGRXRLHCCENI-VOTSOKGWSA-N 4-o-[2-(diethylamino)-2-oxoethyl] 1-o-methyl (e)-but-2-enedioate Chemical compound CCN(CC)C(=O)COC(=O)\C=C\C(=O)OC AKUGRXRLHCCENI-VOTSOKGWSA-N 0.000 description 2
- DNFZKNPDVJWXPG-SNAWJCMRSA-N 4-o-[2-[methoxy(methyl)amino]-2-oxoethyl] 1-o-methyl (e)-but-2-enedioate Chemical compound CON(C)C(=O)COC(=O)\C=C\C(=O)OC DNFZKNPDVJWXPG-SNAWJCMRSA-N 0.000 description 2
- FPIBPYOPUOALEG-MDZDMXLPSA-N 4-o-[4-(cyclohexanecarbonyloxy)butyl] 1-o-methyl (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OCCCCOC(=O)C1CCCCC1 FPIBPYOPUOALEG-MDZDMXLPSA-N 0.000 description 2
- 206010000060 Abdominal distension Diseases 0.000 description 2
- 206010000087 Abdominal pain upper Diseases 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 239000005995 Aluminium silicate Chemical group 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- QRJLNZSFGRNYPE-CMDGGOBGSA-N C(\C=C\C(=O)OCCC)(=O)OOC(=O)OC1CCCCC1 Chemical compound C(\C=C\C(=O)OCCC)(=O)OOC(=O)OC1CCCCC1 QRJLNZSFGRNYPE-CMDGGOBGSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 235000021314 Palmitic acid Nutrition 0.000 description 2
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 229940081735 acetylcellulose Drugs 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 208000024330 bloating Diseases 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- 235000013539 calcium stearate Nutrition 0.000 description 2
- 239000008116 calcium stearate Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
- 229960000590 celecoxib Drugs 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 2
- FBSAITBEAPNWJG-UHFFFAOYSA-N dimethyl phthalate Natural products CC(=O)OC1=CC=CC=C1OC(C)=O FBSAITBEAPNWJG-UHFFFAOYSA-N 0.000 description 2
- LIKFHECYJZWXFJ-UHFFFAOYSA-N dimethyldichlorosilane Chemical compound C[Si](C)(Cl)Cl LIKFHECYJZWXFJ-UHFFFAOYSA-N 0.000 description 2
- 229960001826 dimethylphthalate Drugs 0.000 description 2
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 description 2
- 229940046813 glyceryl palmitostearate Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound 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 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical group O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 2
- 229960000991 ketoprofen Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000000391 magnesium silicate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
- 229960002009 naproxen Drugs 0.000 description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 235000019814 powdered cellulose Nutrition 0.000 description 2
- 229920003124 powdered cellulose Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 2
- 229940083037 simethicone Drugs 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 2
- 239000005052 trichlorosilane Substances 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 125000006686 (C1-C24) alkyl group Chemical group 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
- CDTAOCYIRSSWFZ-SNAWJCMRSA-N 1-O-ethyl 4-O-(methoxycarbonylcarbamoyl) (E)-but-2-enedioate Chemical class C(\C=C\C(=O)OCC)(=O)OC(NC(=O)OC)=O CDTAOCYIRSSWFZ-SNAWJCMRSA-N 0.000 description 1
- KFRXIVFVFSTXDG-SNAWJCMRSA-N 1-O-ethyl 4-O-[(3-methoxy-3-oxopropyl)carbamoyl] (E)-but-2-enedioate Chemical compound C(\C=C\C(=O)OCC)(=O)OC(NCCC(=O)OC)=O KFRXIVFVFSTXDG-SNAWJCMRSA-N 0.000 description 1
- AJVVKLRCOHWRKD-UHFFFAOYSA-N 1-adamantylsilane Chemical compound C1C(C2)CC3CC2CC1([SiH3])C3 AJVVKLRCOHWRKD-UHFFFAOYSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- QZUPVNFKOJRJIV-ONEGZZNKSA-N 1-o-methyl 4-o-(1-morpholin-4-yl-1-oxopropan-2-yl) (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OC(C)C(=O)N1CCOCC1 QZUPVNFKOJRJIV-ONEGZZNKSA-N 0.000 description 1
- AHHOEQGJEPBTLF-ONEGZZNKSA-N 1-o-methyl 4-o-[2-(4-methylpiperazin-1-yl)-2-oxoethyl] (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OCC(=O)N1CCN(C)CC1 AHHOEQGJEPBTLF-ONEGZZNKSA-N 0.000 description 1
- PIPVOAQWMUIOGV-AATRIKPKSA-N 1-o-methyl 4-o-[2-[[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-2-oxoethyl] (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OCC(=O)NCC(=O)OC(C)(C)C PIPVOAQWMUIOGV-AATRIKPKSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Chemical group OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical class OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
- KGNTUCDKGGPQCA-SNAWJCMRSA-N 2-[[2-[(e)-4-methoxy-4-oxobut-2-enoyl]oxyacetyl]amino]butanoic acid Chemical compound CCC(C(O)=O)NC(=O)COC(=O)\C=C\C(=O)OC KGNTUCDKGGPQCA-SNAWJCMRSA-N 0.000 description 1
- PSKGKPIMBDEZHS-ONEGZZNKSA-N 2-[[2-[(e)-4-methoxy-4-oxobut-2-enoyl]oxyacetyl]amino]propanoic acid Chemical compound COC(=O)\C=C\C(=O)OCC(=O)NC(C)C(O)=O PSKGKPIMBDEZHS-ONEGZZNKSA-N 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- KRERQZLVOWHNKJ-BQYQJAHWSA-N 4-O-[bis(2-propan-2-yloxyethyl)carbamoyl] 1-O-ethyl (E)-but-2-enedioate Chemical compound C(\C=C\C(=O)OCC)(=O)OC(N(CCOC(C)C)CCOC(C)C)=O KRERQZLVOWHNKJ-BQYQJAHWSA-N 0.000 description 1
- YHFFINXFNYQPQA-UHFFFAOYSA-N 4-[diethoxy(methyl)silyl]butan-1-amine Chemical compound CCO[Si](C)(OCC)CCCCN YHFFINXFNYQPQA-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- NVRTZTKFMJETFX-MDZDMXLPSA-N 4-o-(1-benzoyloxy-2-methylpropyl) 1-o-methyl (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)OC(C(C)C)OC(=O)C1=CC=CC=C1 NVRTZTKFMJETFX-MDZDMXLPSA-N 0.000 description 1
- PNTZKISLQKVSBW-QRGHLMKCSA-N 4-o-[(2s)-1-[bis(2-methoxyethyl)amino]-1-oxopropan-2-yl] 1-o-methyl (e)-but-2-enedioate Chemical compound COCCN(CCOC)C(=O)[C@H](C)OC(=O)\C=C\C(=O)OC PNTZKISLQKVSBW-QRGHLMKCSA-N 0.000 description 1
- KZCQLFYHSPNDFM-BQYQJAHWSA-N 4-o-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl] 1-o-methyl (e)-but-2-enedioate Chemical compound C1CN(C(=O)COC(=O)/C=C/C(=O)OC)CCN1CC1=CC=CC=C1 KZCQLFYHSPNDFM-BQYQJAHWSA-N 0.000 description 1
- CRLXDCQHMBLGKY-MDZDMXLPSA-N 4-o-[2-[benzyl-(2-ethoxy-2-oxoethyl)amino]-2-oxoethyl] 1-o-methyl (e)-but-2-enedioate Chemical compound COC(=O)/C=C/C(=O)OCC(=O)N(CC(=O)OCC)CC1=CC=CC=C1 CRLXDCQHMBLGKY-MDZDMXLPSA-N 0.000 description 1
- ZYPDERWPXAOYKM-DVJWZOGQSA-N 4-o-[bis[[(e)-4-methoxy-4-oxobut-2-enoyl]oxy]-methylsilyl] 1-o-methyl (e)-but-2-enedioate Chemical compound COC(=O)\C=C\C(=O)O[Si](C)(OC(=O)\C=C\C(=O)OC)OC(=O)\C=C\C(=O)OC ZYPDERWPXAOYKM-DVJWZOGQSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DZKJBZULEJSSKS-AATRIKPKSA-N C(\C=C\C(=O)OCC)(=O)OC(NCCN(C)C)=O Chemical compound C(\C=C\C(=O)OCC)(=O)OC(NCCN(C)C)=O DZKJBZULEJSSKS-AATRIKPKSA-N 0.000 description 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
- MKEBWYCSMZRSJL-VOTSOKGWSA-N CC(C)(/C=C/C)C(N(C)C)=O Chemical compound CC(C)(/C=C/C)C(N(C)C)=O MKEBWYCSMZRSJL-VOTSOKGWSA-N 0.000 description 1
- CHIDSITVESGUDA-FNORWQNLSA-N CCCNC(NC(C(C)(C)/C=C/C)=O)=O Chemical compound CCCNC(NC(C(C)(C)/C=C/C)=O)=O CHIDSITVESGUDA-FNORWQNLSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical class OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 229920003143 Eudragit® FS 30 D Polymers 0.000 description 1
- 229920003163 Eudragit® NE 30 D Polymers 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000005913 Maltodextrin Chemical group 0.000 description 1
- 229920002774 Maltodextrin Chemical group 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- NTYJJOPFIAHURM-HEIOUWIJSA-N N,N,1,1-tetradeuterio-2-(1H-imidazol-5-yl)ethanamine Chemical compound N(C(CC1=CNC=N1)([2H])[2H])([2H])[2H] NTYJJOPFIAHURM-HEIOUWIJSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920001100 Polydextrose Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- FYTPGBJPTDQJCG-UHFFFAOYSA-N Trichloro(chloromethyl)silane Chemical compound ClC[Si](Cl)(Cl)Cl FYTPGBJPTDQJCG-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
- TYVWBCMQECJNSK-UHFFFAOYSA-N [2-methyl-3-(2-methylprop-2-enoyloxy)butan-2-yl]azanium;chloride Chemical compound [Cl-].CC([NH3+])(C)C(C)OC(=O)C(C)=C TYVWBCMQECJNSK-UHFFFAOYSA-N 0.000 description 1
- RQVFGTYFBUVGOP-UHFFFAOYSA-N [acetyloxy(dimethyl)silyl] acetate Chemical compound CC(=O)O[Si](C)(C)OC(C)=O RQVFGTYFBUVGOP-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000007563 acoustic spectroscopy Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000010407 ammonium alginate Nutrition 0.000 description 1
- 239000000728 ammonium alginate Substances 0.000 description 1
- KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 1
- 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- BTSDIPYLHUQCKW-UHFFFAOYSA-N benzenesulfonic acid;ethanesulfonic acid Chemical compound CCS(O)(=O)=O.OS(=O)(=O)C1=CC=CC=C1 BTSDIPYLHUQCKW-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-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)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 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 235000010410 calcium alginate Nutrition 0.000 description 1
- 239000000648 calcium alginate Substances 0.000 description 1
- 229960002681 calcium alginate Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000000828 canola oil Substances 0.000 description 1
- 235000019519 canola oil Nutrition 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940096516 dextrates Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- GNEPOXWQWFSSOU-UHFFFAOYSA-N dichloro-methyl-phenylsilane Chemical compound C[Si](Cl)(Cl)C1=CC=CC=C1 GNEPOXWQWFSSOU-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 208000027692 gas pain Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 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 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 239000000905 isomalt Substances 0.000 description 1
- 235000010439 isomalt Nutrition 0.000 description 1
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 229940059904 light mineral oil Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical group [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Chemical group 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229940037627 magnesium lauryl sulfate Drugs 0.000 description 1
- 239000000395 magnesium oxide Chemical group 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical group [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical group [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 125000005397 methacrylic acid ester group Chemical group 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- LTLRHWVJSDLACP-YDFGWWAZSA-N methyl (E)-4-oxo-4-[(E)-4-oxo-4-propoxybut-2-enoyl]peroxybut-2-enoate Chemical compound C(\C=C\C(=O)OCCC)(=O)OOC(\C=C\C(=O)OC)=O LTLRHWVJSDLACP-YDFGWWAZSA-N 0.000 description 1
- 239000005055 methyl trichlorosilane Substances 0.000 description 1
- JLUFWMXJHAVVNN-UHFFFAOYSA-N methyltrichlorosilane Chemical compound C[Si](Cl)(Cl)Cl JLUFWMXJHAVVNN-UHFFFAOYSA-N 0.000 description 1
- 239000008185 minitablet Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- OKDQKPLMQBXTNH-UHFFFAOYSA-N n,n-dimethyl-2h-pyridin-1-amine Chemical compound CN(C)N1CC=CC=C1 OKDQKPLMQBXTNH-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229960000540 polacrilin potassium Drugs 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 235000013856 polydextrose Nutrition 0.000 description 1
- 239000001259 polydextrose Substances 0.000 description 1
- 229940035035 polydextrose Drugs 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000004300 potassium benzoate Substances 0.000 description 1
- 235000010235 potassium benzoate Nutrition 0.000 description 1
- 229940103091 potassium benzoate Drugs 0.000 description 1
- WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000005029 sieve analysis Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 230000008326 skin blood flow Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 150000003440 styrenes Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- ZOYFEXPFPVDYIS-UHFFFAOYSA-N trichloro(ethyl)silane Chemical compound CC[Si](Cl)(Cl)Cl ZOYFEXPFPVDYIS-UHFFFAOYSA-N 0.000 description 1
- ORVMIVQULIKXCP-UHFFFAOYSA-N trichloro(phenyl)silane Chemical compound Cl[Si](Cl)(Cl)C1=CC=CC=C1 ORVMIVQULIKXCP-UHFFFAOYSA-N 0.000 description 1
- BIBZKNXZTAKPDB-UHFFFAOYSA-N trichloro-(2,3-dichlorophenyl)silane Chemical compound ClC1=CC=CC([Si](Cl)(Cl)Cl)=C1Cl BIBZKNXZTAKPDB-UHFFFAOYSA-N 0.000 description 1
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
Images
Classifications
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Transplantation (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
約43%w/wから約95%w/wの範囲のDMFと、
約3.5%w/wから約55%w/wの範囲の総量の増量剤と、
約0.2%w/wから約20%w/wの範囲の総量の崩壊剤と、
約0.1%w/wから約9.0%w/wの範囲の総量の流動促進剤と、
約0.1%w/wから約3.0%w/wの範囲の総量の滑沢剤
とを含む微小錠剤であって、
微小錠剤が、約25MPaから約200MPaの範囲の加圧力で、約0.5MPaから約5MPaの範囲の引張強度を有し、対応する圧縮成形体が、約100MPaの加圧力で、1.5MPa以上(例えば、2.0〜5.0MPa)の引張強度を有する微小錠剤である。
本明細書で使用する場合、「a」又は「an」は、特に指定しない限り、1つ以上を意味する。
多発性硬化症(MS)は、中枢神経系(CNS)抗原に対する自己免疫活性による自己免疫疾患である。この疾患は、CNSの一部における炎症を特徴とし、その炎症により、神経軸索を覆うミエリンが消失し(脱髄)、軸索が消失し、最終的にニューロン、オリゴデンドロサイト及びグリア細胞が死滅する。MS及び現在の治療法の包括的レビューについては、例えば、Alastair Compstonらによる、McAlpine's Multiple Sclerosis、第4版、Churchill Livingstone Elsevier、2006を参照されたい。
一実施形態においては、多発性硬化症を治療、予防又は改善する方法であって、それを必要とする対象に、MMFへと代謝される化合物又は医薬として許容されるその塩を含有する組成物を投与することを含み、前記組成物投与によって、以下の薬物動態パラメーター、すなわち、(a)約1.5時間から約3.5時間という、MMFの平均血漿中Tmax;(b)約1.03mg/Lから約3.4mg/Lの範囲である、MMFの平均血漿中Cmax;(c)約4.81h.mg/Lから約11.2h.mg/Lの範囲である、MMFの平均血漿中AUCoverall;(d)約2.4h.mg/Lから約5.5h.mg/Lの範囲である、MMFの平均血漿中AUC0-12;及び(e)約2.4h.mg/Lから約5.6h.mg/Lの範囲である平均AUC0-∞のうちの1つ以上が得られる方法である。
R1及びR2は独立に、水素、C1〜6アルキル、及び置換されたC1〜6アルキルから選択され、R3及びR4は独立に、水素、C1〜6アルキル、置換されたC1〜6アルキル、C1〜6ヘテロアルキル、置換されたC1〜6ヘテロアルキル、C4〜12シクロアルキルアルキル、置換されたC4〜12シクロアルキルアルキル、C7〜12アリールアルキル、及び置換されたC7〜12アリールアルキルから選択されるか;R3及びR4は、それらと結合する窒素と一緒になって、C5〜10ヘテロアリール、置換されたC5〜10ヘテロアリール、C5〜10ヘテロシクロアルキル、及び置換されたC5〜10ヘテロシクロアルキルから選択される環を形成し、
R5は、メチル、エチル、及びC3〜6アルキルから選択され、
ここで、各置換基は独立に、ハロゲン、-OH、-CN、-CF3、=O、-NO2、ベンジル、-C(O)NR11 2、-R11、-OR11、-C(O)R11、-COOR11、及び-NR11 2から選択され、ここで、各R11は独立に、水素及びC1〜4アルキルから選択され、
ただし、R5がエチルである場合、R3及びR4は独立に、水素、C1〜6アルキル、及び置換されたC1〜6アルキルから選択される)
又は医薬として許容されるその塩である。
R6は、C1〜6アルキル、置換されたC1〜6アルキル、C1〜6ヘテロアルキル、置換されたC1〜6ヘテロアルキル、C3〜8シクロアルキル、置換されたC3〜8シクロアルキル、C6〜8アリール、置換されたC6〜8アリール、及び-OR10から選択され、ここで、R10は、C1〜6アルキル、置換されたC1〜6アルキル、C3〜10シクロアルキル、置換されたC3〜10シクロアルキル、C6〜10アリール、及び置換されたC6〜10アリールから選択され、
R7及びR8は独立に、水素、C1〜6アルキル、及び置換されたC1〜6アルキルから選択され、R9は、C1〜6アルキル、及び置換されたC1〜6アルキルから選択され、
ここで、各置換基は独立に、ハロゲン、-OH、-CN、-CF3、=O、-NO2、ベンジル、-C(O)NR11 2、-R11、-OR11、-C(O)R11、-COOR11、及び-NR11 2から選択され、ここで、各R11は独立に、水素及びC1〜4アルキルから選択される)
又は医薬として許容されるその塩である。
R2は、C1〜C10アルキル、C5〜C15アリール、ヒドロキシル、-O-C1〜C10アルキル、又は-O-C5〜C15アリールであり;R3、R4及びR5はそれぞれ、独立に、C1〜C10アルキル、C5〜C15アリール、ヒドロキシル、-O-C1〜C10アルキル、-O-C5〜C15アリール、又は
m、n、及びrはそれぞれ、独立に、0〜4であり、
ただし、R3、R4及びR5の少なくとも1つが、
又は医薬として許容されるその塩である。
R2は、C1〜C10アルキル、C6〜C10アリール、ヒドロキシル、-O-C1〜C10アルキル、又は-O-C6〜C10アリールであり;R3、R4及びR5はそれぞれ、独立に、C1〜C10アルキル、C6〜C10アリール、ヒドロキシル、-O-C1〜C10アルキル、-O-C6〜C10アリール、又は
m、n、及びrはそれぞれ、独立に、0〜4であり、
ただし、R3、R4及びR5の少なくとも1つが、
又は医薬として許容されるその塩である。
R2及びR3はそれぞれ、独立に、C1〜C10アルキル又はC5〜C15アリールである)
又は医薬として許容されるその塩である。R2及びR3は、同じ又は異なることができ、場合により置換されていることができ、独立に、C1〜C10アルキル又はC5〜C15アリールからなる群から選択することができる。
R1は、C1〜C24アルキル又はC6〜C10アリールであり、
R2及びR3はそれぞれ、独立に、C1〜C10アルキル又はC6〜C10アリールである)
又は医薬として許容されるその塩である。
R1は、C1〜C24アルキル又はC5〜C50アリールであり、
R2、R3及びR5はそれぞれ、独立に、ヒドロキシル、C1〜C10アルキル、C5〜C15アリール、-O-C1〜C10アルキル、又は-O-C5〜C15アリールであり、
nは、1又は2である)
又は医薬として許容されるその塩である。
R1は、C1〜C24アルキル又はC6〜C10アリールであり、
R2、R3及びR5はそれぞれ、独立に、ヒドロキシル、C1〜C10アルキル、C6〜C10アリール、-O-C1〜C10アルキル、又は-O-C6〜C10アリールであり、
nは、1又は2である)
又は医薬として許容されるその塩である。
R1は、C1〜C24アルキル又はC5〜C50アリールであり、
R2は、C1〜C10アルキルである)
又は医薬として許容されるその塩である。
R1は、C1〜C24アルキル又はC6〜C10アリールであり、
R2は、C1〜C10アルキルである)
又は医薬として許容されるその塩である。
42%w/w及び65%w/wのフマル酸ジメチルを含有する組成物
下の表1に記述した量に従って、フマル酸ジメチル(DMF)、クロスカルメロースナトリウム、タルク、及びコロイド状無水シリカを一緒に混合し、ブレンドを形成した。次いで、ブレンドを、スクリーン(例えば、800ミクロンの穴を有するスクリーン)に通し、微結晶セルロース(PROSOLV SMCC(登録商標)HD90)をブレンドに添加し、混合した。ステアリン酸マグネシウムをブレンドに添加し、ブレンドを再び混合した。次いで、得られたブレンドを、2mmの丸く窪んだチップを有する、16個のチップのマルチチップ工具を備えた、適切な回転式錠剤機で圧縮した。
微小錠剤を含有するカプセルの形成
下の表2に記述した量に従って、フマル酸ジメチル、クロスカルメロースナトリウム、タルカム、及びコロイド状無水シリカを一緒に混合し、ブレンドを形成する。ブレンドを、スクリーンに通す。適切なグレードの微結晶セルロース、例えば、PROSOLV SMCC(登録商標)90、又はPROSOLV SMCC(登録商標)HD90をブレンドに添加し、混合する。ステアリン酸マグネシウムをブレンドに添加し、ブレンドを再び混合する。
微小製剤の形成
下の表3に記述した量に従って、フマル酸ジメチル、クロスカルメロースナトリウム、タルカム、及びコロイド状無水ケイ素を一緒に混合し、ブレンド1、2、4、5及び6を形成した。各ブレンドを、スクリーンに通した。表3中の量に従って、微結晶セルロース(PROSOLV SMCC(登録商標)HD90)を、それらのブレンドに添加し、混合した。次いで、ステアリン酸マグネシウムを各ブレンドに添加し、ブレンドを再び混合した。次いで、各ブレンドを、2mmの丸く窪んだチップを有する、16個のチップのマルチチップ工具を備えた、適切な回転式錠剤機で圧縮した。
42%w/w、60%w/w、及び70%w/wのフマル酸ジメチルを含有する圧縮成形体、並びに対照の圧縮成形体
フマル酸ジメチル、クロスカルメロースナトリウム、及びコロイド状無水シリカを一緒に混ぜ、ブレンドを形成した。ブレンドをスクリーンに通した。スクリーンしたブレンドに適切なグレードの微結晶セルロースを添加し、ブレンドを混合した。適切なグレードの微結晶セルロースは、例えば、レーザー回折による平均粒径が約60μmであり、嵩密度が約0.38〜約0.50g/cm3の範囲であるPROSOLV SMCC(登録商標)90である。ステアリン酸マグネシウムを、混合されたブレンドに添加し、再び混合した。
65%w/w、95%w/w、及び99.5%w/wのフマル酸ジメチルを含有する組成物
DMFを含有する4つのブレンドを、下の表5に記述した量で、実施例4に記述した方法に従って調製した。それらのブレンドの引張強度も、上記した通りに測定し、図3に示した。流動性を、実施例6に記述した通りに測定した。
粉末ブレンドの流動性の測定
FLODEX装置のシリンダーに、粉末試料(例えば、50g)を、シリンダーの最上部から約1cm以内になるように入れた。試験を開始する前に、最低30秒おいた。16mmフローディスクで始めて、遮断物が振動なしで自然に開くまで、解放レバーをゆっくり回した。最上部から見下ろしたときに底部の開口穴が視認可能であった場合、試験は、ポジティブなものであった。ポジティブな結果が得られた場合、試験がネガティブなものになるまで、より小さな穴のディスクで試験を反復した。ネガティブな結果の場合、試験がポジティブなものになるまで、フローディスクの穴のサイズを大きくした。流動性指数は、3連続の試験について試料が通過する、最も小さな穴の直径である。結果を下に示す。
微小錠剤を含有するカプセル中の、120mgのDMF及び240mgのDMFを含有する医薬組成物のPKパラメーターの測定、及び生物学的同等性の評価
81人の対象を登録し、治療シーケンスに無作為化した。
40人の対象が、単一のカプセルとして、DMF240mgの試験製品を経口的に与えられ(投与期間1)、その後、それぞれ120mgのDMFを含有する2つのカプセルとして、参照製品を経口的に与えられる(投与期間2)、シークエンス2。
DMFとアスピリンとの組合せ
健常成人における無作為化、二重盲検、プラセボ対照試験を行った。その試験において、合計56人の対象を、無作為化し、1日2回240mgのDMF、1日3回240mgのDMF、1日2回360mgのDMF、又はプラセボと共に、DMF又はDMFのプラセボ投与の30分前に投与される325mgのアスピリン、又はアスピリンのプラセボによる4日間の治療を受けてもらった。追加の8人の患者を、120mgのDMF、又はプラセボを1日6回(午前中1時間おきに3回投与、さらに、午後に1時間おきに3回投与)投与する修正投与群に割り当てた。追加の2人の対象をプラセボに割り当てた、修正投与計画を除き、一群ごとに6人の対象が存在した。
MMF血漿中濃度-時間の関係(1日目及び4日目)は、すべての治療群について、一様ではなく、個人差が大きかった。アスピリンでの前治療は、どの群の濃度-時間プロファイルにも明らかな効果を与えなかった。大きさにより特徴付けられるが、平均パラメーターは、各治療群内では、1日目及び4日目に関して類似していた。Tmax値は、4時間後に投与される2回目の用量の時に、1回目の用量からの曝露を持ち越せることで予期されたように、一貫して、1日3回の投与の方が1日2日の投与よりも高かった。0〜10時間のAUC(AUC0-10h)値は、用量に比例し、t1/2値は、(一様でない形の濃度-時間プロファイルが、このプロファイルを、特に解釈しにくくさせたが)、非常に短かった。
ステップ2:(E)-O,O'-(ジメチルシランジイル)ジメチルジフマラート11の調製
[実施例10]
メチル((トリメトキシシリル)メチル)フマラート(化合物12)の合成
[実施例11]
メチル((トリヒドロキシシリル)メチル)フマラート(化合物13)の合成
[実施例12]
トリメチル(メチルシラントリイル)トリフマラート(化合物14)の合成
Claims (32)
- フマル酸ジメチルと1種以上の賦形剤とを含む組成物であって、組成物中のフマル酸ジメチルの総量が、約43%w/wから約95%w/wの範囲である組成物。
- 組成物中のフマル酸ジメチルの総量が、約50%w/wから約80%w/wの範囲である、請求項1に記載の組成物。
- 組成物中のフマル酸ジメチルの総量が、約65%w/wである、請求項2に記載の組成物。
- 組成物中のフマル酸ジメチルの総量が、約95%w/wである、請求項1に記載の組成物。
- 1種以上の賦形剤が、1種以上の増量剤、1種以上の崩壊剤、1種以上の流動促進剤、1種以上の滑沢剤、及びそれらの組合せからなる群から選択される、請求項1から4のいずれか一項に記載の組成物。
- 1種以上の賦形剤が、微結晶セルロース、クロスカルメロースナトリウム、コロイド状無水シリカ、ステアリン酸マグネシウム、タルク、及びその組合せからなる群から選択される、請求項4に記載の組成物。
- 組成物が、圧縮成形体の形態をとる、請求項1から6のいずれか一項に記載の組成物。
- 圧縮成形体が、約100MPaの加圧力で、約1.5MPa以上の引張強度を有する、請求項7に記載の組成物。
- 圧縮成形体が、約100MPaの加圧力で、約3.0MPa以上の引張強度を有する、請求項7に記載の組成物。
- 圧縮成形体が、微小錠剤の形態をとる、請求項7に記載の組成物。
- フマル酸ジメチルが、組成物において唯一の活性成分である、請求項10に記載の組成物。
- コーティングされていない微小錠剤が、約1mmから約3mmの範囲の平均直径を有する、請求項10に記載の組成物。
- 微小錠剤が、メタクリル酸-アクリル酸メチルコポリマー、メタクリル酸-アクリル酸エチルコポリマー、メタクリル酸-メチルアクリラートコポリマー、エチルセルロース、ヒドロキシルプロピルセルロース、及びアクリル酸メチル-メタクリル酸メチル-メタクリル酸コポリマーのうち1種以上でコーティングされている、請求項10に記載の組成物。
- 約43%w/wから約95%w/wのフマル酸ジメチルと、総量約3.5%w/wから約55%w/wの1種以上の増量剤と、総量約0.2%w/wから約20%w/wの1種以上の崩壊剤と、総量約0.1%w/wから約9.0%w/wの1種以上の流動促進剤と、総量約0.1%w/wから約3.0%w/wの1種以上の滑沢剤とを含む組成物。
- 組成物が、微小錠剤の形態をとり、前記微小錠剤が、コーティングされておらず、約50%w/wから約95%w/wのフマル酸ジメチルを含有する、請求項14に記載の組成物。
- 約65%w/wのフマル酸ジメチルを含有する、請求項15に記載の組成物。
- 約43%w/wから約95%w/wのフマル酸ジメチル、総量約3.5%w/wから約55%w/wの1種以上の増量剤、総量約0.2%w/wから約20%w/wの1種以上の崩壊剤、総量約0.1%w/wから約9.0%w/wの1種以上の流動促進剤、及び総量約0.1%w/wから約3.0%w/wの1種以上の滑沢剤を合わせて、組成物を形成することを含む、粉末組成物を作製する方法。
- フマル酸ジメチルと、1種以上の賦形剤を含む組成物であって、フマル酸ジメチルの約80%以上が250ミクロン以下の粒径を有する組成物。
- フマル酸ジメチルの約97%以上が250ミクロン以下の粒径を有する、請求項18に記載の組成物。
- 組成物を投与された患者が、約1.5時間から約3.5時間の、フマル酸モノメチルの平均血漿中Tmaxを示す、請求項1に記載の組成物。
- 組成物が、総量約240mgのフマル酸ジメチルを含有する剤形で提供され、その剤形を1日2回投与された患者が、(a)約1.03mg/Lから約2.41mg/Lの範囲である、フマル酸モノメチルの平均血漿中Cmax、及び(b)約4.81h.mg/Lから約11.2h.mg/Lの範囲である、フマル酸モノメチルの平均血漿中AUCoverallからなる群から選択される1つ以上の薬物動態パラメーターを示す、請求項1に記載の組成物。
- 組成物が、総量約240mgのフマル酸ジメチルを含有する剤形で提供され、その剤形を投与された患者が、(a)約1.5mg/Lから約3.4mg/Lの範囲である、フマル酸モノメチルの平均血漿中Cmax、(b)約2.4h.mg/Lから約5.5h.mg/Lの範囲である、フマル酸モノメチルの平均血漿中AUC0-12、及び(c)約2.4h.mg/Lから約5.6h.mg/Lの範囲である平均AUC0-∞からなる群から選択される1つ以上の薬物動態パラメーターを示す、請求項1に記載の組成物。
- フマル酸ジメチルを含む微小錠剤を含んだカプセルであって、コーティングされていない微小錠剤中のフマル酸ジメチルの総量が、約43%w/wから約95%w/wの範囲であるカプセル。
- 微小錠剤が、少なくとも1種のコーティングで部分的又は全体的に腸溶性コーティングされている、請求項23に記載のカプセル。
- 微小錠剤中のフマル酸ジメチルの量が、約60%w/wから約70%w/wであり、カプセルが、約35個から約55個の微小錠剤を含有する、請求項23に記載のカプセル。
- カプセルが、総量約240mgのフマル酸ジメチルを含有し、そのカプセルを投与された患者が、(a)約1.5時間から約3.5時間の、フマル酸モノメチルの平均血漿中Tmax;(b)(a)約1.5mg/Lから約3.4mg/Lの範囲である、フマル酸モノメチルの平均血漿中Cmax、(b)約2.4h.mg/Lから約5.5h.mg/Lの範囲である、フマル酸モノメチルの平均血漿中AUC0-12、及び約2.4h.mg/Lから約5.6h.mg/Lの範囲である平均AUC0-∞からなる群から選択される1つ以上の薬物動態パラメーターを示す、請求項23に記載のカプセル。
- 多発性硬化症(MS)を治療、予防又は改善するための方法であって、それを必要とする対象に、治療有効量のフマル酸ジメチル(DMF)、及び潮紅を軽減するのに有効な量の1種以上の非ステロイド性抗炎症薬を経口投与することを含む方法。
- 前記1種以上の非ステロイド性抗炎症薬が、アスピリンである、請求項27に記載の方法。
- 多発性硬化症を治療、予防又は改善するための方法であって、それを必要とする対象に、フマル酸モノメチルへと代謝される化合物又は医薬として許容されるその塩を含有する組成物を投与することを含み、前記組成物投与によって、以下の薬物動態パラメーター、すなわち、(a)約1.5時間から約3.5時間の、フマル酸モノメチルの平均血漿中Tmax;(b)約1.03mg/Lから約3.4mg/Lの範囲である、フマル酸モノメチルの平均血漿中Cmax;(c)約4.81h.mg/Lから約11.2h.mg/Lの範囲である、フマル酸モノメチルの平均血漿中AUCoverall; (d)約2.4h.mg/Lから約5.5h.mg/Lの範囲である、フマル酸モノメチルの平均血漿中AUC0-12;及び(e)約2.4h.mg/Lから約5.6h.mg/Lの範囲である平均AUC0-∞のうちの1つ以上が得られる方法。
- 組成物が、それを必要とする対象に経口投与される、請求項29に記載の方法。
- フマル酸モノメチルへと代謝される化合物が、式Iの化合物
R1及びR2は独立に、水素、C1〜6アルキル、及び置換されたC1〜6アルキルから選択され、R3及びR4は独立に、水素、C1〜6アルキル、置換されたC1〜6アルキル、C1〜6ヘテロアルキル、置換されたC1〜6ヘテロアルキル、C4〜12シクロアルキルアルキル、置換されたC4〜12シクロアルキルアルキル、C7〜12アリールアルキル、及び置換されたC7〜12アリールアルキルから選択されるか;R3及びR4は、それらと結合する窒素と一緒になって、C5〜10ヘテロアリール、置換されたC5〜10ヘテロアリール、C5〜10ヘテロシクロアルキル、及び置換されたC5〜10ヘテロシクロアルキルから選択される環を形成し、
R5は、メチル、エチル、及びC3〜6アルキルから選択され、
ここで、各置換基は独立に、ハロゲン、-OH、-CN、-CF3、=O、-NO2、ベンジル、-C(O)NR11 2、-R11、-OR11、-C(O)R11、-COOR11、及び-NR11 2から選択され、ここで、各R11は独立に、水素及びC1〜4アルキルから選択され、
ただし、R5がエチルである場合、R3及びR4は独立に、水素、C1〜6アルキル、及び置換されたC1〜6アルキルから選択される)
又は医薬として許容されるその塩である、請求項30に記載の方法。 - フマル酸モノメチルへと代謝される化合物が、式IIの化合物
R6は、C1〜6アルキル、置換されたC1〜6アルキル、C1〜6ヘテロアルキル、置換されたC1〜6ヘテロアルキル、C3〜8シクロアルキル、置換されたC3〜8シクロアルキル、C6〜8アリール、置換されたC6〜8アリール、及び-OR10から選択され、ここで、R10は、C1〜6アルキル、置換されたC1〜6アルキル、C3〜10シクロアルキル、置換されたC3〜10シクロアルキル、C6〜10アリール、及び置換されたC6〜10アリールから選択され、
R7及びR8は独立に、水素、C1〜6アルキル、及び置換されたC1〜6アルキルから選択され、R9は、C1〜6アルキル、及び置換されたC1〜6アルキルから選択され、
ここで、各置換基は独立に、ハロゲン、-OH、-CN、-CF3、=O、-NO2、ベンジル、-C(O)NR11 2、-R11、-OR11、-C(O)R11、-COOR11、及び-NR11 2から選択され、ここで、各R11は独立に、水素及びC1〜4アルキルから選択される)
又は医薬として許容されるその塩である、請求項30に記載の方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2021184462A JP2022024048A (ja) | 2012-02-07 | 2021-11-12 | フマル酸ジメチルを含有する医薬組成物 |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261596202P | 2012-02-07 | 2012-02-07 | |
US61/596,202 | 2012-02-07 | ||
US201261625621P | 2012-04-17 | 2012-04-17 | |
US61/625,621 | 2012-04-17 | ||
US201261723048P | 2012-11-06 | 2012-11-06 | |
US61/723,048 | 2012-11-06 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017149548A Division JP6430598B2 (ja) | 2012-02-07 | 2017-08-02 | フマル酸ジメチルを含有する医薬組成物 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021184462A Division JP2022024048A (ja) | 2012-02-07 | 2021-11-12 | フマル酸ジメチルを含有する医薬組成物 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2019059732A true JP2019059732A (ja) | 2019-04-18 |
Family
ID=48947963
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014555852A Expired - Fee Related JP6189333B2 (ja) | 2012-02-07 | 2013-02-06 | フマル酸ジメチルを含有する医薬組成物 |
JP2017149548A Active JP6430598B2 (ja) | 2012-02-07 | 2017-08-02 | フマル酸ジメチルを含有する医薬組成物 |
JP2018204599A Pending JP2019059732A (ja) | 2012-02-07 | 2018-10-31 | フマル酸ジメチルを含有する医薬組成物 |
JP2021184462A Pending JP2022024048A (ja) | 2012-02-07 | 2021-11-12 | フマル酸ジメチルを含有する医薬組成物 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014555852A Expired - Fee Related JP6189333B2 (ja) | 2012-02-07 | 2013-02-06 | フマル酸ジメチルを含有する医薬組成物 |
JP2017149548A Active JP6430598B2 (ja) | 2012-02-07 | 2017-08-02 | フマル酸ジメチルを含有する医薬組成物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021184462A Pending JP2022024048A (ja) | 2012-02-07 | 2021-11-12 | フマル酸ジメチルを含有する医薬組成物 |
Country Status (24)
Country | Link |
---|---|
US (7) | US20130216615A1 (ja) |
EP (1) | EP2811994A4 (ja) |
JP (4) | JP6189333B2 (ja) |
KR (1) | KR102105217B1 (ja) |
CN (5) | CN104220061A (ja) |
AR (1) | AR089931A1 (ja) |
AU (6) | AU2013203445C1 (ja) |
BR (1) | BR112014019462B1 (ja) |
CA (1) | CA2862885C (ja) |
CL (1) | CL2014002077A1 (ja) |
CO (1) | CO7141407A2 (ja) |
EA (1) | EA038152B1 (ja) |
EC (1) | ECSP14014870A (ja) |
HK (1) | HK1202261A1 (ja) |
IL (2) | IL233833B (ja) |
MX (1) | MX370785B (ja) |
NI (1) | NI201400086A (ja) |
NZ (1) | NZ627980A (ja) |
PE (1) | PE20150092A1 (ja) |
PH (1) | PH12014501750A1 (ja) |
SG (1) | SG11201404705YA (ja) |
TW (4) | TW202102205A (ja) |
WO (1) | WO2013119677A1 (ja) |
ZA (1) | ZA201405511B (ja) |
Families Citing this family (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1663197B1 (en) * | 2003-09-09 | 2007-12-05 | Fumapharm AG | The use of fumaric acid derivatives for treating cardiac insufficiency, and asthma |
LT2801354T (lt) | 2004-10-08 | 2017-06-26 | Forward Pharma A/S | Kontroliuojamo atpalaidavimo farmacinės kompozicijos, apimančios fumaro rūgšties esterį |
HUE032251T2 (en) * | 2007-02-08 | 2017-09-28 | Biogen Ma Inc | Neuroprotection in demyelinating diseases |
MX2011001341A (es) | 2008-08-19 | 2011-03-29 | Xenoport Inc | Prodrogas de metil hidrogeno fumarato, sus composiciones farmaceuticas, y metodos de uso. |
US9422226B2 (en) | 2011-06-08 | 2016-08-23 | Biogen Ma Inc. | Process for preparing high purity and crystalline dimethyl fumarate |
CN104220061A (zh) * | 2012-02-07 | 2014-12-17 | 比奥根艾迪克依蒙菲利亚公司 | 含有富马酸二甲酯的药物组合物 |
US10945984B2 (en) | 2012-08-22 | 2021-03-16 | Arbor Pharmaceuticals, Llc | Methods of administering monomethyl fumarate and prodrugs thereof having reduced side effects |
JP2015526476A (ja) | 2012-08-22 | 2015-09-10 | ゼノポート,インコーポレイティド | メチル水素フマレートの経口剤形およびそのプロドラッグ |
AR094277A1 (es) | 2012-12-21 | 2015-07-22 | Biogen Idec Inc | Derivados de fumarato sustituidos con deuterio |
US8669281B1 (en) | 2013-03-14 | 2014-03-11 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
PT2970101T (pt) | 2013-03-14 | 2018-10-04 | Alkermes Pharma Ireland Ltd | Pró-fármacos de fumaratos e seu uso no tratamento de várias doenças |
WO2014143146A1 (en) * | 2013-03-15 | 2014-09-18 | Xenoport, Inc. | Methods of administering monomethyl fumarate |
US10179118B2 (en) | 2013-03-24 | 2019-01-15 | Arbor Pharmaceuticals, Llc | Pharmaceutical compositions of dimethyl fumarate |
WO2014197860A1 (en) | 2013-06-07 | 2014-12-11 | Xenoport, Inc. | Method of making monomethyl fumarate |
US9421182B2 (en) | 2013-06-21 | 2016-08-23 | Xenoport, Inc. | Cocrystals of dimethyl fumarate |
JP2016534133A (ja) | 2013-09-06 | 2016-11-04 | ゼノポート,インコーポレイティド | (n,n−ジエチルカルバモイル)メチル メチル(2e)ブト−2−エン−1,4−ジオエートの結晶形態、その合成方法及び使用 |
JP6581088B2 (ja) | 2013-12-12 | 2019-09-25 | アルミラル・ソシエダッド・アノニマAlmirall, S.A. | フマル酸ジメチルを含む医薬組成物 |
WO2015089420A1 (en) * | 2013-12-13 | 2015-06-18 | Biogen Idec Ma Inc. | Controlled release dosage form for once daily administration of dimethyl fumarate |
NZ723269A (en) | 2014-02-24 | 2017-04-28 | Alkermes Pharma Ireland Ltd | Sulfonamide and sulfinamide prodrugs of fumarates and their use in treating various diseases |
CA2939990C (en) | 2014-02-28 | 2018-07-10 | Banner Life Sciences Llc | Controlled release enteric soft capsules of fumarate esters |
US10098863B2 (en) | 2014-02-28 | 2018-10-16 | Banner Life Sciences Llc | Fumarate esters |
US9636318B2 (en) | 2015-08-31 | 2017-05-02 | Banner Life Sciences Llc | Fumarate ester dosage forms |
US9326947B1 (en) | 2014-02-28 | 2016-05-03 | Banner Life Sciences Llc | Controlled release fumarate esters |
MA39743A (fr) | 2014-03-14 | 2017-01-18 | Biogen Ma Inc | Fumarate de diméthyle et régimes de vaccination |
US9999672B2 (en) | 2014-03-24 | 2018-06-19 | Xenoport, Inc. | Pharmaceutical compositions of fumaric acid esters |
WO2016057133A1 (en) * | 2014-10-08 | 2016-04-14 | Banner Life Sciences Llc | Controlled release enteric soft capsules of fumarate esters |
SG11201703369WA (en) * | 2014-10-27 | 2017-05-30 | Cellix Bio Private Ltd | Three component salts of fumaric acid monomethyl ester with piperazine or ethylene diamine for the treatment of multiple sclerosis |
MA40985A (fr) | 2014-11-17 | 2017-09-26 | Biogen Ma Inc | Méthodes de traitement de la sclérose en plaques |
MA40982A (fr) * | 2014-11-19 | 2017-09-26 | Biogen Ma Inc | Formulation de bille pharmaceutique comprenant du fumarate de diméthyle |
MA40990A (fr) * | 2014-11-19 | 2017-09-26 | Biogen Ma Inc | Formulations de matrice pharmaceutique comprenant du fumarate de diméthyle |
CN104490849A (zh) * | 2014-11-24 | 2015-04-08 | 广东东阳光药业有限公司 | 一种高密度的富马酸二甲酯肠溶颗粒及其制备方法 |
MA41139A (fr) | 2014-12-11 | 2017-10-17 | Actelion Pharmaceuticals Ltd | Combinaison pharmaceutique comportant un agoniste sélectif du récepteur sip1 |
CN107847451A (zh) * | 2015-02-02 | 2018-03-27 | 英仕柏集团有限责任公司 | 稳定的富马酸二烷基酯组合物 |
HRP20211269T1 (hr) * | 2015-02-08 | 2022-01-21 | Alkermes Pharma Ireland Limited | Kompozicije prolijeka na bazi monometil fumarata |
US20180064653A1 (en) * | 2015-03-17 | 2018-03-08 | Hetero Labs Limited | Pharmaceutical compositions of dimethyl fumarate |
MA41785A (fr) | 2015-03-20 | 2018-01-23 | Biogen Ma Inc | Procédés et compositions pour l'administration intraveineuse de fumarates pour le traitement de maladies neurologiques |
AU2016273068A1 (en) | 2015-06-01 | 2017-12-21 | Sun Pharmaceutical Industries Ltd. | Pharmaceutical compositions of dimethyl fumarate |
CN107920997A (zh) | 2015-06-17 | 2018-04-17 | 比奥根Ma公司 | 富马酸二甲酯颗粒和其药物组合物 |
WO2017056107A1 (en) * | 2015-09-28 | 2017-04-06 | Natco Pharma Ltd | Pharmaceutical compositions of dimethyl fumarate |
MX2018005345A (es) * | 2015-10-28 | 2018-08-14 | Sun Pharmaceutical Ind Ltd | Composiciones farmaceuticas de dimetil fumarato. |
CA3007483C (en) | 2015-12-31 | 2021-12-07 | Zaklady Farmaceutyczne Polpharma S.A. | Process for preparation of an enteric coated granulate comprising dimethyl fumarate |
WO2017129370A1 (en) * | 2016-01-28 | 2017-08-03 | Zaklady Farmaceutyczne Polpharma S.A. | Process for preparation of a granulate comprising dimethyl fumarate |
CA3013472A1 (en) | 2016-02-11 | 2017-08-17 | Biogen Ma Inc. | Pharmaceutical bead formulations comprising dimethyl fumarate |
WO2017145036A1 (en) * | 2016-02-25 | 2017-08-31 | Aurobindo Pharma Ltd | Pharmaceutical compositions comprising dimethyl fumarate |
TR201616998A1 (en) | 2016-11-23 | 2018-06-21 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | DELAYED RELEASE DOSING FORMS WITH DIMETHYL FUMARATE |
CN110475547A (zh) * | 2017-03-17 | 2019-11-19 | 维塔利斯公司 | 治疗多发性硬化症的组合物和方法 |
KR20200018458A (ko) | 2017-06-23 | 2020-02-19 | 알미랄, 에스.에이. | 디메틸 푸마레이트를 포함하는 약학 조성물 |
US20210251910A1 (en) * | 2018-09-10 | 2021-08-19 | Vitalis Llc | Fumaric acid compositions with increased bioavailability and reduced side effects |
US11446055B1 (en) | 2018-10-18 | 2022-09-20 | Lumoptik, Inc. | Light assisted needle placement system and method |
TR201818293A2 (tr) | 2018-11-30 | 2020-06-22 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Di̇meti̇l fumarat i̇çeren geci̇kmeli̇ salim sağlayan kapsül |
US11903918B2 (en) | 2020-01-10 | 2024-02-20 | Banner Life Sciences Llc | Fumarate ester dosage forms with enhanced gastrointestinal tolerability |
AU2021208602A1 (en) | 2020-05-06 | 2022-12-15 | Imcyse Sa | Combination treatment for fumarate-related diseases |
WO2022254356A1 (en) * | 2021-06-04 | 2022-12-08 | Zim Laboratories Limited | Delayed release compositions of dimethyl fumarate |
US20240010618A1 (en) | 2021-12-23 | 2024-01-11 | Glenmark Lofe Science Limited | Process for the preparation of brivaracetam |
CN115590831A (zh) * | 2022-10-26 | 2023-01-13 | 力品药业(厦门)股份有限公司(Cn) | 一种富马酸二甲酯缓释微片及其制备方法 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002525276A (ja) * | 1998-08-31 | 2002-08-13 | フーマファーム アーゲー | フマル酸誘導体を含有する移植医療における治療剤 |
JP2002530324A (ja) * | 1998-11-19 | 2002-09-17 | フーマファーム アーゲー | ジアルキルフマレートの使用 |
JP2003529556A (ja) * | 2000-01-10 | 2003-10-07 | フーマファーム アーゲー | フマル酸誘導体を使用したミトコンドリア病治療用薬剤組成物 |
JP2008515822A (ja) * | 2004-10-08 | 2008-05-15 | アディテック・ファルマ・アクチボラゲット | フマル酸エステルを含む制御放出医薬組成物 |
JP2008529959A (ja) * | 2003-09-09 | 2008-08-07 | フーマファーム アーゲー | 心不全並びに喘息治療のためのフマル酸誘導体含有薬剤 |
JP2011521915A (ja) * | 2008-05-20 | 2011-07-28 | セレニス セラピューティクス エス.エー. | ナイアシン及びnsaid併用療法 |
JP2012500285A (ja) * | 2008-08-19 | 2012-01-05 | ゼノポート,インコーポレイティド | メチル水素フマレートのプロドラッグ、その医薬組成物及び使用方法 |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1153927A (en) | 1966-08-25 | 1969-06-04 | Wilhelm Hoerrmann | Medicinal Composition Suitable For Treating Diseases Of The Retina |
US5424332A (en) | 1987-10-19 | 1995-06-13 | Speiser; Peter P. | Pharmaceutical composition and process for the production thereof |
US4959389A (en) | 1987-10-19 | 1990-09-25 | Speiser Peter P | Pharmaceutical preparation for the treatment of psoriatic arthritis |
US5484610A (en) | 1991-01-02 | 1996-01-16 | Macromed, Inc. | pH and temperature sensitive terpolymers for oral drug delivery |
DE19721099C2 (de) | 1997-05-20 | 1999-12-02 | Fumapharm Ag Muri | Verwendung von Fumarsäurederivaten |
FI109088B (fi) * | 1997-09-19 | 2002-05-31 | Leiras Oy | Tabletti ja menetelmä sen valmistamiseksi |
DE19814358C2 (de) | 1998-03-31 | 2002-01-17 | Fumapharm Ag Muri | Verwendung von Alkylhydrogenfumaraten zur Behandlung von Psoriasis, psoriatischer Arthritis, Neurodermitis und Enteritis regionalis Crohn |
DE19848260C2 (de) * | 1998-10-20 | 2002-01-17 | Fumapharm Ag Muri | Fumarsäure-Mikrotabletten |
US6537584B1 (en) | 1999-11-12 | 2003-03-25 | Macromed, Inc. | Polymer blends that swell in an acidic environment and deswell in a basic environment |
US6399101B1 (en) | 2000-03-30 | 2002-06-04 | Mova Pharmaceutical Corp. | Stable thyroid hormone preparations and method of making same |
CN101961317A (zh) | 2001-07-06 | 2011-02-02 | 生命周期药物公司 | 受控制的凝聚 |
KR100540035B1 (ko) * | 2002-02-01 | 2005-12-29 | 주식회사 태평양 | 다단계 경구 약물 방출 제어 시스템 |
DE10214031A1 (de) | 2002-03-27 | 2004-02-19 | Pharmatech Gmbh | Verfahren zur Herstellung und Anwendung von Mikro- und Nanoteilchen durch aufbauende Mikronisation |
NZ542303A (en) * | 2003-03-14 | 2008-12-24 | Nirmal Mulye | A process for preparing sustained release tablets |
EP1663197B1 (en) * | 2003-09-09 | 2007-12-05 | Fumapharm AG | The use of fumaric acid derivatives for treating cardiac insufficiency, and asthma |
CN101056624A (zh) * | 2004-10-08 | 2007-10-17 | Adi技术制药股份公司 | 包含富马酸酯的控释药物组合物 |
WO2007006307A2 (en) * | 2005-07-07 | 2007-01-18 | Aditech Pharma Ab | Novel salts of fumaric acid monoalkylesters and their pharmaceutical use |
JP2009510137A (ja) | 2005-10-07 | 2009-03-12 | アディテック・ファルマ・アクチボラゲット | フマル酸エステルを含む制御放出医薬組成物 |
WO2007042035A2 (en) | 2005-10-07 | 2007-04-19 | Aditech Pharma Ab | Combination therapy with fumaric acid esters for the treatment of autoimmune and/or inflammatory disorders |
JP2009522272A (ja) * | 2005-12-30 | 2009-06-11 | ミドルブルック ファーマスーティカルス,インコーポレイテッド | 薬剤送達のための胃内放出パルスシステム |
MX2009011493A (es) * | 2007-04-25 | 2009-11-09 | Teva Pharma | Complejo de excipiente farmaceutico. |
EP2227226B1 (en) * | 2007-12-21 | 2016-10-26 | Johnson & Johnson Consumer Inc. | Manufacture of a tablet |
US8906420B2 (en) * | 2009-01-09 | 2014-12-09 | Forward Pharma A/S | Pharmaceutical formulation comprising one or more fumaric acid esters in an erosion matrix |
US20120034274A1 (en) | 2009-01-09 | 2012-02-09 | Forward Pharma A/S | Pharmaceutical composition comprising one or more fumaric acid esters |
EP3466420A1 (en) * | 2009-04-29 | 2019-04-10 | Biogen MA Inc. | Dimethyl fumarate for the treatment of friedreich ataxia |
US20100285164A1 (en) | 2009-05-11 | 2010-11-11 | Jrs Pharma | Orally Disintegrating Excipient |
HUE025878T2 (en) | 2010-02-12 | 2016-05-30 | Biogen Ma Inc | Neuroprotection in demyelinating diseases |
CN104220061A (zh) * | 2012-02-07 | 2014-12-17 | 比奥根艾迪克依蒙菲利亚公司 | 含有富马酸二甲酯的药物组合物 |
-
2013
- 2013-02-06 CN CN201380018792.9A patent/CN104220061A/zh active Pending
- 2013-02-06 WO PCT/US2013/024946 patent/WO2013119677A1/en active Application Filing
- 2013-02-06 PE PE2014001232A patent/PE20150092A1/es not_active Application Discontinuation
- 2013-02-06 EA EA201491484A patent/EA038152B1/ru unknown
- 2013-02-06 CN CN202111172018.6A patent/CN114146080A/zh active Pending
- 2013-02-06 MX MX2014009469A patent/MX370785B/es active IP Right Grant
- 2013-02-06 CN CN202111173089.8A patent/CN114146081A/zh active Pending
- 2013-02-06 EP EP13746306.3A patent/EP2811994A4/en active Pending
- 2013-02-06 NZ NZ627980A patent/NZ627980A/en unknown
- 2013-02-06 JP JP2014555852A patent/JP6189333B2/ja not_active Expired - Fee Related
- 2013-02-06 KR KR1020147024886A patent/KR102105217B1/ko active IP Right Grant
- 2013-02-06 CN CN202110490355.3A patent/CN113244185A/zh active Pending
- 2013-02-06 CN CN202111171982.7A patent/CN114146079A/zh active Pending
- 2013-02-06 AU AU2013203445A patent/AU2013203445C1/en active Active
- 2013-02-06 CA CA2862885A patent/CA2862885C/en active Active
- 2013-02-06 SG SG11201404705YA patent/SG11201404705YA/en unknown
- 2013-02-06 US US13/760,916 patent/US20130216615A1/en not_active Abandoned
- 2013-02-06 BR BR112014019462-9A patent/BR112014019462B1/pt active IP Right Grant
- 2013-02-07 TW TW109108318A patent/TW202102205A/zh unknown
- 2013-02-07 TW TW110139187A patent/TW202231268A/zh unknown
- 2013-02-07 TW TW102104904A patent/TWI676475B/zh active
- 2013-02-07 AR ARP130100385A patent/AR089931A1/es not_active Application Discontinuation
- 2013-02-07 TW TW106127330A patent/TWI697338B/zh active
- 2013-03-14 US US13/827,228 patent/US20130295169A1/en not_active Abandoned
- 2013-04-12 AU AU2013204286A patent/AU2013204286B2/en active Active
-
2014
- 2014-07-25 ZA ZA2014/05511A patent/ZA201405511B/en unknown
- 2014-07-28 IL IL233833A patent/IL233833B/en unknown
- 2014-08-04 PH PH12014501750A patent/PH12014501750A1/en unknown
- 2014-08-06 NI NI201400086A patent/NI201400086A/es unknown
- 2014-08-06 CL CL2014002077A patent/CL2014002077A1/es unknown
- 2014-08-20 EC ECIEPI201414870A patent/ECSP14014870A/es unknown
- 2014-09-05 CO CO14196527A patent/CO7141407A2/es unknown
-
2015
- 2015-03-18 HK HK15102805.4A patent/HK1202261A1/xx unknown
- 2015-04-06 US US14/679,716 patent/US20150209318A1/en not_active Abandoned
-
2017
- 2017-01-20 AU AU2017200394A patent/AU2017200394B2/en active Active
- 2017-07-28 AU AU2017208367A patent/AU2017208367A1/en not_active Abandoned
- 2017-08-02 JP JP2017149548A patent/JP6430598B2/ja active Active
-
2018
- 2018-03-02 US US15/910,745 patent/US20180185319A1/en not_active Abandoned
- 2018-05-24 US US15/988,568 patent/US20180263946A1/en not_active Abandoned
- 2018-10-31 JP JP2018204599A patent/JP2019059732A/ja active Pending
- 2018-11-09 AU AU2018260937A patent/AU2018260937B2/en active Active
-
2019
- 2019-08-05 US US16/532,155 patent/US20190358190A1/en not_active Abandoned
-
2020
- 2020-03-23 US US16/826,938 patent/US20200222354A1/en not_active Abandoned
- 2020-09-28 AU AU2020244395A patent/AU2020244395B2/en not_active Expired - Fee Related
-
2021
- 2021-11-12 JP JP2021184462A patent/JP2022024048A/ja active Pending
-
2022
- 2022-02-06 IL IL290378A patent/IL290378B2/en unknown
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002525276A (ja) * | 1998-08-31 | 2002-08-13 | フーマファーム アーゲー | フマル酸誘導体を含有する移植医療における治療剤 |
JP2002530324A (ja) * | 1998-11-19 | 2002-09-17 | フーマファーム アーゲー | ジアルキルフマレートの使用 |
JP2003529556A (ja) * | 2000-01-10 | 2003-10-07 | フーマファーム アーゲー | フマル酸誘導体を使用したミトコンドリア病治療用薬剤組成物 |
JP2008529959A (ja) * | 2003-09-09 | 2008-08-07 | フーマファーム アーゲー | 心不全並びに喘息治療のためのフマル酸誘導体含有薬剤 |
JP2008515822A (ja) * | 2004-10-08 | 2008-05-15 | アディテック・ファルマ・アクチボラゲット | フマル酸エステルを含む制御放出医薬組成物 |
JP2011521915A (ja) * | 2008-05-20 | 2011-07-28 | セレニス セラピューティクス エス.エー. | ナイアシン及びnsaid併用療法 |
JP2012500285A (ja) * | 2008-08-19 | 2012-01-05 | ゼノポート,インコーポレイティド | メチル水素フマレートのプロドラッグ、その医薬組成物及び使用方法 |
Non-Patent Citations (1)
Title |
---|
改訂 医薬品添加物ハンドブック, vol. 第5版, JPN6016042727, 2007, pages 276 - 309, ISSN: 0004689113 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6430598B2 (ja) | フマル酸ジメチルを含有する医薬組成物 | |
TW201622721A (zh) | S1p調節劑之立即釋放劑量療法 | |
EA037666B1 (ru) | Фармацевтическая композиция, содержащая 2-(2,5-диоксопирролидин-1-ил)этилметилфумарат, и ее применение в медицине | |
JPH04290824A (ja) | 医薬の新規活性成分としてのカルバゾンの用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181130 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190108 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191001 |
|
RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7426 Effective date: 20191209 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20191223 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20191209 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200331 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200825 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20201117 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210219 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210518 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210805 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20220125 |