JP6581088B2 - フマル酸ジメチルを含む医薬組成物 - Google Patents
フマル酸ジメチルを含む医薬組成物 Download PDFInfo
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- JP6581088B2 JP6581088B2 JP2016538622A JP2016538622A JP6581088B2 JP 6581088 B2 JP6581088 B2 JP 6581088B2 JP 2016538622 A JP2016538622 A JP 2016538622A JP 2016538622 A JP2016538622 A JP 2016538622A JP 6581088 B2 JP6581088 B2 JP 6581088B2
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- dimethyl fumarate
- calcium
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- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 title claims description 86
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 83
- 229960004419 dimethyl fumarate Drugs 0.000 title claims description 58
- 239000000203 mixture Substances 0.000 claims description 52
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 42
- 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 claims description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 239000008101 lactose Substances 0.000 claims description 36
- 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 claims description 35
- 238000000576 coating method Methods 0.000 claims description 34
- 239000011248 coating agent Substances 0.000 claims description 33
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 31
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 31
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- 229920002472 Starch Polymers 0.000 claims description 30
- 235000019698 starch Nutrition 0.000 claims description 30
- 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 28
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 27
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 27
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 27
- 201000006417 multiple sclerosis Diseases 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 24
- 239000008107 starch Substances 0.000 claims description 24
- 239000003085 diluting agent Substances 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 22
- 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 claims description 21
- 239000000377 silicon dioxide Substances 0.000 claims description 19
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 18
- 201000004681 Psoriasis Diseases 0.000 claims description 18
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims description 18
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 18
- 235000010355 mannitol Nutrition 0.000 claims description 18
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 18
- 229930195725 Mannitol Natural products 0.000 claims description 17
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 17
- 230000002757 inflammatory effect Effects 0.000 claims description 17
- 239000000594 mannitol Substances 0.000 claims description 17
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 16
- 208000035475 disorder Diseases 0.000 claims description 16
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- 239000000314 lubricant Substances 0.000 claims description 14
- 208000023275 Autoimmune disease Diseases 0.000 claims description 13
- 229930091371 Fructose Natural products 0.000 claims description 13
- 239000005715 Fructose Substances 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 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 claims description 12
- 229960001031 glucose Drugs 0.000 claims description 12
- 235000019359 magnesium stearate Nutrition 0.000 claims description 12
- 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 claims description 11
- 208000027866 inflammatory disease Diseases 0.000 claims description 11
- 239000000454 talc Substances 0.000 claims description 11
- 229910052623 talc Inorganic materials 0.000 claims description 11
- 235000012222 talc Nutrition 0.000 claims description 11
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 10
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 10
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 9
- 208000011231 Crohn disease Diseases 0.000 claims description 9
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 9
- 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 claims description 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 9
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 9
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 claims description 9
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 8
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 claims description 8
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 8
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 claims description 8
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound 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 claims description 7
- 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 claims description 7
- 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 claims description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 229930006000 Sucrose Natural products 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 239000000905 isomalt Substances 0.000 claims description 7
- 235000010439 isomalt Nutrition 0.000 claims description 7
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- 235000010356 sorbitol Nutrition 0.000 claims description 7
- 239000000600 sorbitol Substances 0.000 claims description 7
- 229960002920 sorbitol Drugs 0.000 claims description 7
- 239000005720 sucrose Substances 0.000 claims description 7
- 239000008121 dextrose Substances 0.000 claims description 6
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 6
- 239000001095 magnesium carbonate Substances 0.000 claims description 6
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 6
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 5
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 5
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 5
- 235000010216 calcium carbonate Nutrition 0.000 claims description 5
- 229930182830 galactose Natural products 0.000 claims description 5
- 235000014380 magnesium carbonate Nutrition 0.000 claims description 5
- 235000010449 maltitol Nutrition 0.000 claims description 5
- 239000000845 maltitol Substances 0.000 claims description 5
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 5
- 229940035436 maltitol Drugs 0.000 claims description 5
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 5
- 235000012239 silicon dioxide Nutrition 0.000 claims description 5
- 239000001069 triethyl citrate Substances 0.000 claims description 5
- 235000013769 triethyl citrate Nutrition 0.000 claims description 5
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000811 xylitol Substances 0.000 claims description 5
- 235000010447 xylitol Nutrition 0.000 claims description 5
- 229960002675 xylitol Drugs 0.000 claims description 5
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
- 235000011132 calcium sulphate Nutrition 0.000 claims description 4
- 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 claims description 4
- 230000002496 gastric effect Effects 0.000 claims description 4
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 4
- 239000000391 magnesium silicate Substances 0.000 claims description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 4
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 239000008119 colloidal silica Substances 0.000 claims description 3
- 229940037627 magnesium lauryl sulfate Drugs 0.000 claims description 3
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 239000000378 calcium silicate Substances 0.000 claims description 2
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 2
- 235000012241 calcium silicate Nutrition 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 claims description 2
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- 235000019793 magnesium trisilicate Nutrition 0.000 claims description 2
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 2
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 2
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
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- 229960002739 oxaprozin Drugs 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 229960000649 oxyphenbutazone Drugs 0.000 description 1
- HFHZKZSRXITVMK-UHFFFAOYSA-N oxyphenbutazone Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 HFHZKZSRXITVMK-UHFFFAOYSA-N 0.000 description 1
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- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
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- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
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- 229920001282 polysaccharide Polymers 0.000 description 1
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- 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
- 238000005070 sampling Methods 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 229950005175 sudoxicam Drugs 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
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- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960004492 suprofen Drugs 0.000 description 1
- 230000003746 surface roughness Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229960002871 tenoxicam Drugs 0.000 description 1
- WZWYJBNHTWCXIM-UHFFFAOYSA-N tenoxicam Chemical compound O=C1C=2SC=CC=2S(=O)(=O)N(C)C1=C(O)NC1=CC=CC=N1 WZWYJBNHTWCXIM-UHFFFAOYSA-N 0.000 description 1
- 150000003538 tetroses Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- YEZNLOUZAIOMLT-UHFFFAOYSA-N tolfenamic acid Chemical compound CC1=C(Cl)C=CC=C1NC1=CC=CC=C1C(O)=O YEZNLOUZAIOMLT-UHFFFAOYSA-N 0.000 description 1
- 229960002905 tolfenamic acid Drugs 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- OFVFGKQCUDMLLP-UHFFFAOYSA-N tribuzone Chemical compound O=C1C(CCC(=O)C(C)(C)C)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 OFVFGKQCUDMLLP-UHFFFAOYSA-N 0.000 description 1
- 229950000919 tribuzone Drugs 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
- 229960004418 trolamine Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- 238000013389 whole blood assay Methods 0.000 description 1
- 229940057977 zinc stearate Drugs 0.000 description 1
- 229930195727 α-lactose Natural products 0.000 description 1
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Description
本発明はさらに、これらの組成物を投与することによる、いくつかの炎症性自己免疫疾患または障害の治療方法に関する。
さらに、錠剤は25℃を超えない温度で保存しなくてはならない。(Fumaderm(登録商標)initial(イニシャル)/Fumaderm(登録商標);製品概要、2009年2月版)。
Tecfidera(登録商標)は、120mgまたは240mgのフマル酸ジメチル、および以下の賦形剤を含む経口投与用の遅延放出型硬ゼラチンカプセルとして提供されている:微結晶性セルロース、ケイ化微結晶性セルロース、クロスカルメロースナトリウム、タルク、コロイド状シリカ二酸化ケイ素(silica colloidal silicon dioxide)、ステアリン酸マグネシウム、クエン酸トリエチル、メタクリル酸共重合体−A型、メタクリル酸共重合体分散液、シメチコン(30%乳濁液)、ラウリル硫酸ナトリウムおよびポリソルベート 80。さらに、カプセルは15〜25℃で保存しなくてはならない(承認された2013年3月27日付けのTecfidera(登録商標)のラベル表示)。
Tecfidera(登録商標)は、用量を漸増させながら、最初の7日間は120mgを1日2回、その後240mg用量を1日2回投与しなければならない。
本明細書で用いられるように、用語「治療」は、以下のものを含むヒト患者における疾患または医学的状態の治療を指す:
(a)疾患または医学的状態の発生を予防すること、すなわち患者の予防的治療、
(b)疾患または医学的状態を改善すること、すなわち患者における疾患または医学的状態の退行をもたらすこと、
(c)疾患または医学的状態を抑制すること、すなわち患者における疾患または医学的状態の進行を減速させること、あるいは、
(d)患者における疾患または医学的状態の症状を低減すること。
フマル酸ジメチル(ジメチル(E)−ブテンジオエート;CAS登録番号 624−49−7)はフマル酸のメチルエステルであり、分子式 C6H8O4、分子量 144.13g/mol、および以下の化学式を示す。
2004年のドイツ薬局方(DAC 2004)によると、融点が102〜105℃の範囲内である白色結晶性粉末である。
フマル酸ジメチルの結晶学的特性は、Kooijman H et al, Acta Cryst. (2004), E60, o917-o918に記載されている。
フマル酸ジメチルは、触媒として濃硫酸の存在下でフマル酸とメタノールを反応させることにより得ることができる(Ma Hongfei, Chemical industry Times, 2005, Vol. 19, No. 4, 18-19)。
典型的には、フマル酸ジメチルは、篩過および/または粉砕してその粒子径を制御する。好ましい態様において、レーザー回折粒径分析器 Mastersizer 2000(Malvern Instruments)を用いて測定されるフマル酸ジメチルの粒子径分布は、d(10)が5〜20μmの間、d(50)が30〜70μmの間、およびd(90)が80〜150μmの間である。
希釈剤は、剤型、すなわち錠剤の必要なバルクを構成するのに指定される増量剤であり、薬物用量それ自体ではこのバルクをもたらすのに不十分な場合に用いられる(The Theory and Practice of Industrial Pharmacy, 3rd edition, 1986, ISBN 0-8121-0977-5)。
典型的には、希釈剤は、単糖、二糖、デンプンおよびデンプン誘導体、カルシウムおよびマグネシウム無機塩、糖アルコール、並びにその混合物から選ばれる。
フルクトース(D−フルクトース)は、強い甘味がある、無臭の無色結晶または白色結晶性粉末として存在する単糖である(CAS登録番号 57−48−7;分子式 C6H12O6;分子量 180.16g/m)。フルクトースは蜂蜜および多くの果物中に天然に存在する。フルクトースは、イヌリン、デキストロースまたはスクロースから多くの方法により調製してもよい。商業的には、フルクトースは主に、加水分解および異性化された穀類デンプン、または甘蔗糖および甜菜糖から誘導される高フルクトースシロップから結晶化により製造される(Handbook of Pharmaceutical Excipients, 6th edition, 2009)。
ラクトースは乳から得られ、1つのガラクトースと1つのグルコース部分からなる天然の単糖である。ラクトースは、白色〜黄色がかった白色の結晶性粒子または粉末として存在する。ラクトースは無臭であり、わずかな甘味がある。The Handbook of Pharmaceutical Excipients, 6th edition, 2009には、本発明に照らして適切な様々なラクトースの種類が記載されている:無水ラクトース(CAS登録番号 63−42−3;分子式 C12H22O11;分子量 342.30g/m)、吸入ラクトース、ラクトース一水和物(CAS登録番号 5989−81−1;分子式 C12H22O11.H2O;分子量 360.31g/m)、並びに非結晶質ラクトース(α−およびβ−ラクトースの1:1混合物)およびラクトース一水和物の混合物である噴霧乾燥ラクトース。
典型的には、噴霧乾燥ラクトースのかさ密度は0.55〜0.68g/cm3の間、タップ密度は0.65〜0.75g/cm3の間である。好ましい態様において、噴霧乾燥ラクトースの粒子径分布(エアジェットシーブ上に保持されるもの、積算)は、60〜80%が75μm(米国規格 #200)、30〜55%が106μm(米国規格 #140)、および0.0〜0.5%が250μm(米国規格 #60)である。
本発明のリン酸水素カルシウムは、無水リン酸水素カルシウムおよびリン酸水素カルシウム水和物を指す。
マンニトール(D−マンニトール;CAS登録番号 69−65−8;分子式 C6H14O6;分子量 182.17g/m)は、マンノースに関連がありソルビトールの異性体である六水酸基アルコールである。マンニトールは、無臭の白色の結晶性粉末または自由流動性の顆粒として存在する。マンニトールは、およそ、グルコースと同程度、スクロースの半分程度の甘味があり、口内で冷却感を感じさせる。The Handbook of Pharmaceutical Excipients, 6th edition, 2009には、Pearlitol 300 DC、Pearlitol 400 DCおよびPearlitol 500 DC(全てRoquette Freresにより製造されている)のような、本発明に照らして適切な様々なグレードの市販のマンニトールが記載されている。
微結晶性セルロース(CAS登録番号 9004−34−6;分子式 (C6H10O5)n、式中nは約220;分子量 約36000g/m)は、多孔質粒子からなる無味無臭の白色結晶性粉末として存在する、精製され部分的に解重合したセルロースである(Handbook of Pharmaceutical Excipients, 6th edition, 2009)。
典型的には、微結晶性セルロースのかさ密度は0.28〜0.33g/cm3の間である。好ましい態様において、レーザー回折粒径分析器 Mastersizer 2000(Malvern Instruments)を用いて測定される微結晶性セルロースの粒子径分布は、d(10)が25〜50μmの間、d(50)が100〜150μmの間、およびd(90)が195〜280μmの間である。
クロスカルメロースナトリウム(セルロース、カルボキシメチルエーテル、ナトリウム 塩、架橋物;CAS登録番号 74811−65−7)は、カルボキシメチルセルロースナトリウムの架橋重合体である。クロスカルメロースナトリウムは、無臭の白色または灰色がかった白色の粉末として存在する(Handbook of Pharmaceutical Excipients, 6th edition, 2009)。
典型的には、クロスカルメロースナトリウムのかさ密度は約0.529g/cm3、タップ密度は約0.819g/cm3である。好ましい態様において、レーザー回折粒径分析器 Mastersizer 2000(Malvern Instruments)を用いて測定される微結晶性セルロースの粒子径分布は、d(10)が25μm以下、d(50)が25〜55μmの間、およびd(90)が60μm以上である。
典型的には、本発明は、(a)フマル酸ジメチル、(b)単糖、二糖、デンプンおよびデンプン誘導体、カルシウムおよびマグネシウム無機塩、糖アルコール、およびその混合物から選ばれる希釈剤、(c)微結晶性セルロース、並びに(d)クロスカルメロースナトリウムを含み、フマル酸ジメチルが胃耐性コーティングで覆われていない、医薬組成物を提供する。
(a)20〜30重量%のフマル酸ジメチル(胃耐性コーティングで覆われていない);
(b)ラクトース、D−グルコース(デキストロース)、スクロース、フルクトース、ガラクトース、デンプン、炭酸カルシウム、リン酸水素カルシウム、硫酸カルシウム、炭酸マグネシウム、イソマルト、マンニトール、マルチトール、ソルビトール、キシリトール、およびその混合物から選ばれる、25〜35重量%の希釈剤;
(c)35〜45重量%の微結晶性セルロース;
(d)1〜10重量%のクロスカルメロースナトリウム。
(a)20〜30重量%のフマル酸ジメチル(予め胃耐性コーティングで覆われていない);
(b)ラクトース、リン酸水素カルシウム、イソマルト、マンニトール、およびその混合物から選ばれる、25〜35重量%の希釈剤;
(c)35〜45重量%の微結晶性セルロース;
(d)1〜10重量%のクロスカルメロースナトリウム。
(a)20〜30重量%のフマル酸ジメチル(予め胃耐性コーティングで覆われていない);
(b)25〜35重量%のラクトース;
(c)35〜45重量%の微結晶性セルロース;
(d)1〜10重量%のクロスカルメロースナトリウム。
(a)20〜30重量%のフマル酸ジメチル(予め胃耐性コーティングで覆われていない);
(b)25〜35重量%のラクトース;
(c)35〜45重量%の微結晶性セルロース;
(d)1〜10重量%のクロスカルメロースナトリウム;
(e)好ましくは、コロイド状無水シリカ、タルク、またはその組み合わせ、より好ましくはコロイド状無水シリカから選ばれる、0.1〜5重量%の少なくとも1つの流動促進剤;
(f)0.1〜10重量%の少なくとも1つの滑沢剤、好ましくはステアリン酸マグネシウム。
(a)25重量%のフマル酸ジメチル(予め胃耐性コーティングで覆われていない);
(b)30重量%のラクトース;
(c)40重量%の微結晶性セルロース;
(d)4重量%のクロスカルメロースナトリウム;
(e)好ましくは、コロイド状無水シリカ、タルク、またはその組み合わせ、より好ましくはコロイド状無水シリカから選ばれる、0.5重量%の少なくとも1つの流動促進剤;
(f)0.5重量%の少なくとも1つの滑沢剤、好ましくはステアリン酸マグネシウム。
(a)30mgのフマル酸ジメチル(予め胃耐性コーティングで覆われていない);
(b)36mgのラクトース;
(c)48mgの微結晶性セルロース;
(d)4.8mgのクロスカルメロースナトリウム;
(e)0.6mgのコロイド状無水シリカ;
(f)0.6mgのステアリン酸マグネシウム。
(a)120mgのフマル酸ジメチル(予め胃耐性コーティングで覆われていない);
(b)144mgのラクトース;
(c)192mgの微結晶性セルロース;
(d)19.2mgのクロスカルメロースナトリウム;
(e)2.4mgのコロイド状無水シリカ;
(f)2.4mgのステアリン酸マグネシウム。
i)(a)予め胃耐性コーティングで覆われていないフマル酸ジメチル、(b)単糖、二糖、デンプンおよびデンプン誘導体、カルシウムおよびマグネシウム無機塩、糖アルコール、およびその混合物から選ばれる希釈剤、(c)微結晶性セルロース、(d)クロスカルメロースナトリウム、並びに適宜他の医薬賦形剤を混合して均一な配合物を形成する工程;並びに
ii)適宜配合物を篩過する工程。
本発明はまた、この方法により得られうる医薬組成物も提供する。
i)(a)予め胃耐性コーティングで覆われていないフマル酸ジメチル、(b)単糖、二糖、デンプンおよびデンプン誘導体、カルシウムおよびマグネシウム無機塩、糖アルコール、およびその混合物から選ばれる希釈剤、(c)微結晶性セルロース、(d)クロスカルメロースナトリウム、並びに(e)少なくとも1つの流動促進剤を混合して均一な配合物を形成する工程;
ii)適宜配合物を篩過する工程;
iii)前記の配合物に(e)少なくとも1つの流動促進剤を加え、得られた配合物を混合する工程;並びに
iv)適宜最終配合物を篩過する工程。
本発明はまた、この方法により得られうる医薬組成物にも関する。
i)上記の配合物を打錠して錠剤コアを得る工程;および
ii)錠剤コアのコーティング工程。
本発明はまた、この方法により得られうる胃耐性(腸溶コート)錠も提供する。
60kgのバルク組成物は、表1に詳細に記載した量の成分を混合することにより調製した。
フマル酸ジメチル、ラクトース、微結晶性セルロース、クロスカルメロースナトリウムおよびコロイド状無水シリカを混合して配合物を形成した。次いで配合物を0.8mmふるいに通した。篩過した配合物を再び混合した。次いで得られたものを再び0.8mmふるいに通し、最後に再び混合した。
ステアリン酸マグネシウムを0.5mmふるいに通し、上記の配合物に加え、混合して最終配合物を得た。
2.1.本発明の錠剤
実施例1の最終配合物を2つの相似の部分に分けて含量(フマル酸ジメチル30および120mg)が異なる錠剤を得た。12kgのバルク組成物をロータリー式打錠機を用いて直接圧縮により打錠し、最終重量が120mg(フマル酸ジメチル30mg)、直径が6.5mmの、100,000の錠剤コアを得た。
48kgのバルク組成物をロータリー式打錠機を用いて直接圧縮により打錠し、最終重量が480mg(120mgのフマル酸ジメチル)、直径が11mmの、100,000の錠剤コアを得た。
次いで錠剤コアを、水およびメタクリル酸−アクリル酸エチル共重合体(1:1)30%水性分散液に懸濁したクエン酸トリエチル、シメチコン、タルクおよび二酸化チタンを含む水性フィルムコーティング懸濁液でコーティングした(表2中の量を参照のこと)。120mgのフマル酸ジメチル錠剤コアの場合、コーティング懸濁液にはまた、インジゴカルミン・レーキおよび水酸化ナトリウムも含めた。
上記と同様に、フマル酸ジメチル30および120mg腸溶コート錠を、表3、4および5中に示されるように、ラクトースを、フルクトース、マンニトールおよびリン酸水素カルシウム(CaHPO4 2H2O)で置き換えて調製した。この錠剤を用いて、気候室内で、相対湿度40℃/75%で6ヶ月間、安定性試験を実施した。結果から、錠剤が安定であると結論づけた。
上記と同様に、フマル酸ジメチル120mg腸溶コート錠を、ラクトースを微結晶性セルロースで置き換えて調製した。この錠剤を用いて、気候室内で、相対湿度40℃/75%で6ヶ月間、安定性試験を実施した。結果から、錠剤が安定でないと結論づけた。
固形剤型用の標準の溶出試験に従って、上記の本発明の腸溶コート錠におけるフマル酸ジメチルの溶出速度を決定した。これらの溶出試験は、European Pharmacopoeia 6.0, Chapter 2.9.3、およびUS Pharmacopoiea USP36-NF31, Chapter 711に記載されている。
Claims (16)
- (a)フマル酸ジメチル、(b)フルクトース、ラクトース、リン酸水素カルシウム、マンニトールおよびその混合物から選ばれる希釈剤、(c)微結晶性セルロース、並びに(d)クロスカルメロースナトリウムを含む、胃耐性医薬組成物であって、クエン酸トリエチルを含むコーティングで覆われている、医薬組成物。
- フマル酸ジメチルが胃耐性コーティングで覆われていない、請求項1に記載の医薬組成物。
- (a)フマル酸ジメチル、(b)ラクトース、(c)微結晶性セルロース、および(d)クロスカルメロースナトリウムを含む、請求項1または2に記載の医薬組成物。
- さらに(e)少なくとも1つの流動促進剤を含む、請求項1〜3のいずれか一項に記載の医薬組成物。
- 流動促進剤(e)が、リン酸カルシウム、ケイ酸カルシウム、粉末セルロース、ケイ酸マグネシウム、三ケイ酸マグネシウム、二酸化ケイ素、タルク、コロイド状シリカ、コロイド状無水シリカ、およびその混合物から選ばれる、請求項4に記載の医薬組成物。
- さらに(f)少なくとも1つの滑沢剤を含む、請求項1〜5のいずれか一項に記載の医薬組成物。
- 滑沢剤(f)が、ステアリン酸マグネシウム、ステアリン酸カルシウム、フマル酸ステアリルナトリウム、ポリエチレングリコール、ラウリル硫酸ナトリウム、ラウリル硫酸マグネシウム、安息香酸ナトリウム、安息香酸カリウム、軽油、硬化植物油、モノステアリン酸グリセリン、ベヘン酸グリセリル、パルミトステアリン酸グリセリル、ステアリン酸、ステアリン酸亜鉛、およびその混合物から選ばれる、請求項6に記載の医薬組成物。
- (c)微結晶性セルロースの(b)希釈剤に対する重量比が2:5〜5:2の範囲内である、請求項1〜7のいずれか一項に記載の医薬組成物。
- 組成物が経口投与される、請求項1〜8のいずれか一項に記載の医薬組成物。
- 錠剤の形態をとる、請求項1〜9のいずれか一項に記載の医薬組成物。
- コーティングされる前の錠剤の総重量に基づいて、
(a)20〜30重量%のフマル酸ジメチル;
(b)ラクトース、D−グルコース(デキストロース)、スクロース、フルクトース、ガラクトース、デンプン、炭酸カルシウム、リン酸水素カルシウム、硫酸カルシウム、炭酸マグネシウム、イソマルト、マンニトール、マルチトール、ソルビトール、キシリトール、およびその混合物から選ばれる、25〜35重量%の希釈剤;
(c)35〜45重量%の微結晶性セルロース;
(d)1〜10重量%のクロスカルメロースナトリウム
を含む、請求項10に記載の医薬組成物。 - さらに(e)少なくとも1つの流動促進剤を含む、請求項11に記載の医薬組成物。
- さらに(f)少なくとも1つの滑沢剤を含む、請求項11または請求項12に記載の医薬組成物。
- コーティングされる前の錠剤の総重量に基づいて、
(a)25重量%のフマル酸ジメチル;
(b)30重量%のラクトース;
(c)40重量%の微結晶性セルロース;
(d)4重量%のクロスカルメロースナトリウム;
(e)0.5重量%の少なくとも1つの流動促進剤;
(f)0.5重量%の少なくとも1つの滑沢剤
を含む、請求項11〜13のいずれか一項に記載の医薬組成物。 - 炎症性または自己免疫性の疾患または障害、特に、リウマチ性関節炎、多発性硬化症(MS)、筋萎縮性側索硬化症、クローン病、潰瘍性大腸炎、全身性エリテマトーデス(SLE)、重症筋無力症、急性播種性脳脊髄炎、特発性血小板減少性紫斑病、シェーグレン症候群、自己免疫性溶血性貧血(AIHA)、1型糖尿病または乾癬から選ばれる炎症性または自己免疫性の疾患または障害の治療または予防に用いるための、請求項1〜14のいずれか一項に定義される医薬組成物。
- 炎症性または自己免疫性の疾患または障害、特に、リウマチ性関節炎、多発性硬化症(MS)、筋萎縮性側索硬化症、クローン病、潰瘍性大腸炎、全身性エリテマトーデス(SLE)、重症筋無力症、急性播種性脳脊髄炎、特発性血小板減少性紫斑病、シェーグレン症候群、自己免疫性溶血性貧血(AIHA)、1型糖尿病または乾癬から選ばれる炎症性または自己免疫性の疾患または障害の治療または予防のための薬剤を製造するための、請求項1〜14のいずれか一項に定義される医薬組成物の使用。
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Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9636318B2 (en) | 2015-08-31 | 2017-05-02 | Banner Life Sciences Llc | Fumarate ester dosage forms |
US9326965B2 (en) | 2014-02-28 | 2016-05-03 | Banner Life Sciences Llc | Controlled release fumarate esters |
US10098863B2 (en) | 2014-02-28 | 2018-10-16 | Banner Life Sciences Llc | Fumarate esters |
US9326947B1 (en) | 2014-02-28 | 2016-05-03 | Banner Life Sciences Llc | Controlled release fumarate esters |
US10085961B2 (en) | 2015-06-01 | 2018-10-02 | Sun Pharmaceutical Industries Limited | Pharmaceutical compositions of dimethyl fumarate |
US10744070B2 (en) | 2015-06-19 | 2020-08-18 | University Of Southern California | Enteral fast access tract platform system |
CA2990230A1 (en) | 2015-06-19 | 2016-12-22 | University Of Southern California | Compositions and methods for modified nutrient delivery |
WO2017040272A1 (en) * | 2015-08-31 | 2017-03-09 | Banner Life Sciences Llc | Fumarate ester dosage forms |
BR112018013184A2 (pt) * | 2015-12-31 | 2018-12-11 | Zaklady Farmaceutyczne Polpharma S.A. | processo para preparação de um granulado revestido entérico compreendendo dimetilfumarato |
EP3407873B1 (en) * | 2016-01-28 | 2024-08-21 | Zaklady Farmaceutyczne Polpharma S.A. | Process for preparation of a granulate comprising dimethyl fumarate |
JP2019510743A (ja) * | 2016-02-12 | 2019-04-18 | ウニヴェルズィテート チューリッヒ | 痛風、ざ瘡及び糖尿病の予防又は治療のためのジメチルフマレート(dmf) |
WO2017145036A1 (en) * | 2016-02-25 | 2017-08-31 | Aurobindo Pharma Ltd | Pharmaceutical compositions comprising dimethyl fumarate |
MA49448A (fr) | 2017-06-23 | 2020-04-29 | Almirall Sa | Compositions pharmaceutiques contenant du fumarate de diméthyle |
JP7000148B2 (ja) * | 2017-12-27 | 2022-01-19 | 日本化薬株式会社 | ダサチニブを有効成分とする医薬組成物 |
WO2020053218A1 (en) | 2018-09-13 | 2020-03-19 | Almirall, S.A. | Treatment of psoriasis |
WO2020053219A1 (en) | 2018-09-13 | 2020-03-19 | Almirall, S.A. | Treatment of psoriasis |
JP7224067B2 (ja) * | 2019-05-31 | 2023-02-17 | キュラクル カンパニー リミテッド | フマル酸ジメチルを含有する腸溶性錠剤 |
JP6744518B1 (ja) * | 2019-11-07 | 2020-08-19 | 旭化成株式会社 | セルロース組成物及び錠剤 |
WO2021142062A1 (en) | 2020-01-10 | 2021-07-15 | Banner Life Sciences Llc | Fumarate ester dosage forms with enhanced gastrointestinal tolerability |
EP4313023A1 (en) * | 2021-04-02 | 2024-02-07 | Biogen MA Inc. | Combination treatment methods of multiple sclerosis |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4959389A (en) | 1987-10-19 | 1990-09-25 | Speiser Peter P | Pharmaceutical preparation for the treatment of psoriatic arthritis |
DE19848260C2 (de) | 1998-10-20 | 2002-01-17 | Fumapharm Ag Muri | Fumarsäure-Mikrotabletten |
DE19853487A1 (de) * | 1998-11-19 | 2000-05-25 | Fumapharm Ag Muri | Verwendung von Dialkylfumaraten |
DE10101307A1 (de) * | 2001-01-12 | 2002-08-01 | Fumapharm Ag Muri | Fumarsäurederivate als NF-kappaB-Inhibitor |
DE202005022112U1 (de) * | 2004-10-08 | 2014-04-24 | Forward Pharma A/S | Pharmazeutische Zusammensetzungen mit kontrollierter Freisetzung, umfassend einen Fumarsaureester |
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 |
ES2340518T3 (es) * | 2005-04-28 | 2010-06-04 | Wyeth Llc | Tanaproget micronizado y composiciones que lo contienen. |
EP1940382A2 (en) * | 2005-10-07 | 2008-07-09 | Aditech Pharma AB | Combination therapy with fumaric acid esters for the treatment of autoimmune and/or inflammatory disorders |
WO2007042034A1 (en) * | 2005-10-07 | 2007-04-19 | Aditech Pharma Ab | Controlled release pharmaceutical compositions comprising a fumaric acid ester |
CN101304732A (zh) * | 2005-10-07 | 2008-11-12 | Adi技术制药股份公司 | 包含富马酸酯的控释药物组合物 |
WO2009118764A1 (en) * | 2008-03-28 | 2009-10-01 | Panacea Biotec Limited | Pharmaceutical composition comprising diclofenac and paracetamol |
US20120034274A1 (en) | 2009-01-09 | 2012-02-09 | Forward Pharma A/S | Pharmaceutical composition comprising one or more fumaric acid esters |
RU2743637C2 (ru) | 2009-01-09 | 2021-02-20 | Фвп Ип Апс | Фармацевтический состав, содержащий один или более эфиров фумаровой кислоты в разлагаемой матрице |
CA2760133A1 (en) * | 2009-04-29 | 2010-11-04 | Biogen Idec Ma Inc. | Treatment of neurodegeneration and neuroinflammation |
AR086647A1 (es) * | 2011-06-03 | 2014-01-15 | Hoffmann La Roche | Metodos para tratar el mesotelioma con un compuesto inhibidor de la pi3k |
WO2013076216A1 (en) | 2011-11-24 | 2013-05-30 | Synthon Bv | Controlled release particles comprising dimethyl fumarate |
AU2013203445C1 (en) | 2012-02-07 | 2017-04-20 | Biogen Ma Inc. | Pharmaceutical compositions containing dimethyl fumarate |
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