ES2659771T3 - Procedimiento de preparación de fumarato de dimetilo cristalino y de alta pureza - Google Patents
Procedimiento de preparación de fumarato de dimetilo cristalino y de alta pureza Download PDFInfo
- Publication number
- ES2659771T3 ES2659771T3 ES12796164.7T ES12796164T ES2659771T3 ES 2659771 T3 ES2659771 T3 ES 2659771T3 ES 12796164 T ES12796164 T ES 12796164T ES 2659771 T3 ES2659771 T3 ES 2659771T3
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- Prior art keywords
- dimethyl fumarate
- reaction
- approximately
- methanol
- dimethyl
- 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.)
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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 abstract description 114
- 229960004419 dimethyl fumarate Drugs 0.000 title claims abstract description 114
- 238000002360 preparation method Methods 0.000 title description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 259
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims abstract description 110
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims abstract description 61
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 60
- 238000000034 method Methods 0.000 claims abstract description 56
- 239000000203 mixture Substances 0.000 claims abstract description 50
- 239000001530 fumaric acid Substances 0.000 claims abstract description 49
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims abstract description 43
- 239000011541 reaction mixture Substances 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims description 74
- 239000002245 particle Substances 0.000 claims description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 49
- 230000008569 process Effects 0.000 claims description 14
- 230000002829 reductive effect Effects 0.000 claims description 14
- 239000000463 material Substances 0.000 claims description 7
- 230000002035 prolonged effect Effects 0.000 claims description 3
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 38
- 239000000047 product Substances 0.000 description 36
- -1 methyl hydrogen hydrogen fumarate Chemical compound 0.000 description 29
- 230000015572 biosynthetic process Effects 0.000 description 23
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- 239000000243 solution Substances 0.000 description 19
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000001035 drying Methods 0.000 description 16
- 238000005886 esterification reaction Methods 0.000 description 16
- 230000007062 hydrolysis Effects 0.000 description 16
- 238000006460 hydrolysis reaction Methods 0.000 description 16
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
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- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 4
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- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
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- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/297—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
- C07C69/593—Dicarboxylic acid esters having only one carbon-to-carbon double bond
- C07C69/60—Maleic acid esters; Fumaric acid esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
- C07C69/604—Polycarboxylic acid esters, the acid moiety containing more than two carboxyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
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- Health & Medical Sciences (AREA)
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- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
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| PCT/US2012/041715 WO2012170923A1 (en) | 2011-06-08 | 2012-06-08 | Process for preparing high purity and crystalline dimethyl fumarate |
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| EP1913942B1 (en) | 2003-09-09 | 2009-11-11 | Biogen Idec International GmbH | The use of fumaric acid derivatives for inhibition of PGF-induced thymidine uptake of bronchial smooth muscle cells and for inhibition of bronchial smooth cells proliferation |
| PL2316430T3 (pl) | 2004-10-08 | 2012-11-30 | Forward Pharma As | Kompozycje farmaceutyczne o kontrolowanym uwalnianiu, zawierające ester kwasu fumarowego |
| HRP20140640T1 (hr) | 2008-08-19 | 2014-11-21 | Xenoport, Inc. | Prolijekovi monometil estera fumarne kiseline, farmaceutski sastavi iz toga i postupci njihove uporabe |
| KR20140035995A (ko) | 2011-06-08 | 2014-03-24 | 바이오겐 아이덱 엠에이 인코포레이티드 | 고순도 및 결정질 다이메틸 푸마레이트의 제조 방법 |
| EP2887935A1 (en) | 2012-08-22 | 2015-07-01 | XenoPort, Inc. | Oral dosage forms of methyl hydrogen fumarate and prodrugs thereof |
| CA2882713A1 (en) | 2012-08-22 | 2014-02-27 | Xenoport, Inc. | Methods of administering monomethyl fumarate and prodrugs thereof having reduced side effects |
| JP6506174B2 (ja) | 2012-12-21 | 2019-04-24 | バイオジェン エムエー インコーポレイテッド | 重水素置換されたフマル酸誘導体 |
| PT2970101T (pt) | 2013-03-14 | 2018-10-04 | Alkermes Pharma Ireland Ltd | Pró-fármacos de fumaratos e seu uso no tratamento de várias doenças |
| US8669281B1 (en) | 2013-03-14 | 2014-03-11 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
| WO2014160633A1 (en) | 2013-03-24 | 2014-10-02 | Xenoport, Inc. | Pharmaceutical compositions of dimethyl fumarate |
| CN104098471A (zh) * | 2013-04-03 | 2014-10-15 | 南京卡文迪许生物工程技术有限公司 | 富马酸二甲酯多晶型物及其制备方法和药物组合物 |
| WO2014197860A1 (en) | 2013-06-07 | 2014-12-11 | Xenoport, Inc. | Method of making monomethyl fumarate |
| WO2014205392A1 (en) | 2013-06-21 | 2014-12-24 | Xenoport, Inc. | Cocrystals of dimethyl fumarate |
| TW201516020A (zh) | 2013-09-06 | 2015-05-01 | Xenoport Inc | （ｎ，ｎ－二乙基胺甲醯基）甲基（２ｅ）丁－２－烯－１，４－二酸甲酯之晶形、合成方法及用途 |
| IN2013MU03070A (enExample) * | 2013-09-25 | 2015-07-17 | Glenmark Pharmaceuticals Ltd | |
| IN2014CH00308A (enExample) * | 2014-01-24 | 2015-07-31 | Shilpa Medicare Ltd | |
| CA2940845C (en) | 2014-02-24 | 2019-09-24 | Alkermes Pharma Ireland Limited | Sulfonamide and sulfinamide prodrugs of fumarates and their use in treating various diseases |
| 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 |
| ES2713157T3 (es) | 2014-02-28 | 2019-05-20 | Banner Life Sciences Llc | Cápsulas blandas entéricas de liberación controlada de ésteres de fumarato |
| US9636318B2 (en) | 2015-08-31 | 2017-05-02 | Banner Life Sciences Llc | Fumarate ester dosage forms |
| US10626076B2 (en) * | 2014-03-17 | 2020-04-21 | Biophore India Pharmaeuticals Pvt. Ltd. | Process for the synthesis of dimethyl fumarate |
| US9999672B2 (en) | 2014-03-24 | 2018-06-19 | Xenoport, Inc. | Pharmaceutical compositions of fumaric acid esters |
| EP3164378A1 (en) * | 2014-07-03 | 2017-05-10 | Synthon B.V. | Process for making microcrystalline dimethyl fumarate |
| CN104151165B (zh) * | 2014-08-11 | 2016-08-24 | 广东东阳光药业有限公司 | 制备富马酸二甲酯的方法 |
| CN104761453A (zh) * | 2015-04-22 | 2015-07-08 | 河南中帅医药科技股份有限公司 | 一种富马酸二甲酯晶型及其制备方法 |
| US10085961B2 (en) * | 2015-06-01 | 2018-10-02 | Sun Pharmaceutical Industries Limited | Pharmaceutical compositions of dimethyl fumarate |
| AU2016279997B2 (en) * | 2015-06-17 | 2021-10-21 | Biogen Ma Inc. | Dimethyl fumarate particles and pharmaceutical compositions thereof |
| CN106316841A (zh) * | 2015-06-30 | 2017-01-11 | 深圳翰宇药业股份有限公司 | 一种富马酸二甲酯的制备方法 |
| WO2017013672A1 (en) * | 2015-07-23 | 2017-01-26 | Natco Pharma Ltd | Process for the preparation of pharmaceutical grade dimethyl fumarate |
| US10011663B2 (en) | 2016-02-04 | 2018-07-03 | Eastman Chemical Company | Vulcanizing composition containing cyclododecasulfur and improved cyclododecasulfur compound |
| RU2616605C1 (ru) * | 2016-04-07 | 2017-04-18 | Олег Ростиславович Михайлов | Кристаллическая бета - модификация (Е)-диметилбутендиоата, способ её получения и фармацевтическая композиция на её основе |
| CN107285320A (zh) * | 2017-08-02 | 2017-10-24 | 内蒙古新福地科技有限公司 | 一种氟硅酸钠的结晶方法及装置 |
| CN111201235B (zh) * | 2017-10-10 | 2023-02-10 | 辉瑞公司 | 劳拉替尼游离碱水合物的结晶形式 |
| WO2021142062A1 (en) | 2020-01-10 | 2021-07-15 | Banner Life Sciences Llc | Fumarate ester dosage forms with enhanced gastrointestinal tolerability |
| KR102271575B1 (ko) * | 2020-09-16 | 2021-07-01 | 김갑용 | 염의 이온교환법을 이용한 친환경 고효율 에스터화반응 기반의 에스터화합물 제조방법 및 이의 화합물 |
| JP6865489B1 (ja) * | 2020-10-20 | 2021-04-28 | 株式会社エス・ディー・エス バイオテック | ２，３，５，６−テトラクロロ−１，４−ベンゼンジカルボン酸ジメチルの製造方法 |
| CN117550970A (zh) * | 2023-10-30 | 2024-02-13 | 寿光金远东变性淀粉有限公司 | 一种高纯度衣康酸二甲酯的生产方法 |
Family Cites Families (86)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1848724A (en) | 1932-03-08 | Alphons | ||
| US2764609A (en) * | 1953-07-24 | 1956-09-25 | Monsanto Chemicals | Isomerization of dialkyl maleates to dialkyl fumarates |
| US3078302A (en) * | 1958-09-25 | 1963-02-19 | Monsanto Chemicals | Production of dialkyl fumarates |
| US3993684A (en) | 1971-08-20 | 1976-11-23 | Western Litho Plate & Supply Co. | Monomeric compounds |
| US5118835A (en) | 1976-09-24 | 1992-06-02 | Exxon Research & Engineering Co. | Thio-bis(alkyl lactone acid esters) and thio-bis (Hydrocarbyl diacid esters) are usefull additives for lubricating compositions |
| US4568756A (en) | 1976-09-24 | 1986-02-04 | Exxon Research & Engineering Co. | Thio-bis-(alkyl lactone acid esters) and thio-bis-(hydrocarbyl diacid esters) are useful additives for lubricating compositions |
| US4239636A (en) | 1978-10-23 | 1980-12-16 | Exxon Research & Engineering Co. | Thio-bis-(alkyl lactone acid esters) and thio-bis-(hydrocarbyl diacid esters) are useful additives for lubricating compositions |
| US4866187A (en) | 1976-09-24 | 1989-09-12 | Exxon Research & Engineering Company | Thio-bis(alkyl lactone acid esters) and thio-bis-(hydrocarbyl diacid esters) are useful additives for lubricating compositions |
| US4965375A (en) | 1976-09-24 | 1990-10-23 | Exxon Research And Engineering Co. | Thio-bis-(alkyl lactone acid esters) and thio-bis-(hydrocarbyl diacid esters) are useful additives for lubricating compositions |
| US4417062A (en) | 1976-09-24 | 1983-11-22 | Exxon Research & Engineering Co. | Thio-bis-(alkyl lactone acid esters) and thio-bis-(hydrocarbyl diacid esters) are useful additives for lubricating compositions |
| JPS60193946U (ja) | 1984-03-01 | 1985-12-24 | 内山 茂夫 | 変色炎を有するろうそく |
| JPS60193946A (ja) * | 1984-03-16 | 1985-10-02 | Nippon Oil & Fats Co Ltd | ジイソプロピルフマレ−トの製造法 |
| CH664150A5 (de) | 1985-01-15 | 1988-02-15 | Peter Paul Prof Dr Speiser | Fumarsaeureprodrug, verfahren zu seiner herstellung und dieses enthaltende darreichungsformen. |
| US5149695A (en) | 1985-01-15 | 1992-09-22 | Speiser Peter P | Fumaric acid derivatives, process for the production thereof and pharmaceutical compositions containing same |
| JPS61246147A (ja) * | 1985-04-22 | 1986-11-01 | Nippon Shokubai Kagaku Kogyo Co Ltd | マレイン酸ジアルキルエステルの精製方法 |
| US4954277A (en) | 1986-10-07 | 1990-09-04 | Exxon Chemical Patents Inc. | Lactone modified, esterified or aminated additives useful in oleaginous compositions and compositions containing same |
| US4954276A (en) | 1986-10-07 | 1990-09-04 | Exxon Chemical Patents Inc. | Lactone modified adducts or reactants and oleaginous compositions containing same |
| US5032320A (en) | 1986-10-07 | 1991-07-16 | Exxon Chemical Patents Inc. | Lactone modified mono- or dicarboxylic acid based adduct dispersant compositions |
| US4906394A (en) | 1986-10-07 | 1990-03-06 | Exxon Chemical Patents Inc. | Lactone modified mono-or dicarboxylic acid based adduct dispersant compositions |
| US4866140A (en) | 1986-10-07 | 1989-09-12 | Exxon Chemical Patents Inc. | Lactone modified adducts or reactants and oleaginous compositions containing same |
| US4866139A (en) | 1986-10-07 | 1989-09-12 | Exxon Chemical Patents Inc. | Lactone modified, esterified dispersant additives useful in oleaginous compositions |
| US4963275A (en) | 1986-10-07 | 1990-10-16 | Exxon Chemical Patents Inc. | Dispersant additives derived from lactone modified amido-amine adducts |
| DE3711155A1 (de) * | 1987-04-02 | 1988-10-13 | Bayer Ag | Verfahren zur herstellung von maleinsaeuredimethylester |
| US4820432A (en) | 1987-07-24 | 1989-04-11 | Exxon Chemical Patents Inc. | Lactone-modified, Mannich base dispersant additives useful in oleaginous compositions |
| US4971711A (en) | 1987-07-24 | 1990-11-20 | Exxon Chemical Patents, Inc. | Lactone-modified, mannich base dispersant additives useful in oleaginous compositions |
| US4959389A (en) | 1987-10-19 | 1990-09-25 | Speiser Peter P | Pharmaceutical preparation for the treatment of psoriatic arthritis |
| US5424332A (en) | 1987-10-19 | 1995-06-13 | Speiser; Peter P. | Pharmaceutical composition and process for the production thereof |
| US4943382A (en) | 1988-04-06 | 1990-07-24 | Exxon Chemical Patents Inc. | Lactone modified dispersant additives useful in oleaginous compositions |
| US5153352A (en) | 1988-10-25 | 1992-10-06 | Bristol-Myers Squibb Company | Process for preparation of intermediates of carbocyclic nucleoside analogs |
| ATE154365T1 (de) | 1993-01-21 | 1997-06-15 | Akzo Nobel Nv | Lufttrocknende wässrige polymerdispersionen |
| CN1103398A (zh) * | 1993-11-30 | 1995-06-07 | 张治明 | 一种由顺酐生产富马酸二甲酯的工艺方法 |
| AU3881695A (en) | 1994-11-21 | 1996-06-17 | Asahi Kasei Kogyo Kabushiki Kaisha | Curable resin and composition |
| CA2258875A1 (en) | 1996-06-24 | 1997-12-31 | Cytec Technology Corp. | Polymerizable urea/ureido functional monomers |
| US6239189B1 (en) | 1997-04-01 | 2001-05-29 | Henkel Corporation | Radiation-polymerizable composition and printing inks containing same |
| DE19721099C2 (de) | 1997-05-20 | 1999-12-02 | Fumapharm Ag Muri | Verwendung von Fumarsäurederivaten |
| WO1999002482A1 (fr) | 1997-07-11 | 1999-01-21 | Showa Denko K.K. | Composes a base d'ether et procede de production |
| US6376702B1 (en) | 1997-07-11 | 2002-04-23 | Showa Denko K.K. | Ether compound, production thereof and curable compositions |
| GB9724004D0 (en) | 1997-11-13 | 1998-10-21 | Kvaerner Process Tech Ltd | Process |
| 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 |
| DE19839566C2 (de) | 1998-08-31 | 2002-01-17 | Fumapharm Ag Muri | Verwendung von Fumarsäurederivaten in der Transplantationsmedizin |
| 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 |
| US7056965B2 (en) | 1999-12-27 | 2006-06-06 | Asahi Kasei Kabushiki Kaisha | Polyoxymethylene resin composition |
| DE10000577A1 (de) | 2000-01-10 | 2001-07-26 | Fumapharm Ag Muri | Verwendung von Fumarsäurederivaten zur Behandlung mitochondrialer Krankheiten |
| US20020002306A1 (en) * | 2000-02-15 | 2002-01-03 | Yasushi Kadowaki | Method for producing fumaric acid esters |
| JP2001281800A (ja) | 2000-03-31 | 2001-10-10 | Konica Corp | 熱現像写真感光材料 |
| US6586452B1 (en) | 2000-07-14 | 2003-07-01 | Merck & Co., Inc. | C1 to C4 side chain modified nodulisporic acid analogs |
| US20020098451A1 (en) | 2000-09-07 | 2002-07-25 | Tadashi Arimoto | Photothermographic material |
| DE10101307A1 (de) | 2001-01-12 | 2002-08-01 | Fumapharm Ag Muri | Fumarsäurederivate als NF-kappaB-Inhibitor |
| SK288238B6 (sk) | 2001-01-12 | 2015-01-07 | Fumapharm Ag | Amidy kyseliny fumarovej |
| JP2003160535A (ja) * | 2001-11-28 | 2003-06-03 | Nof Corp | 不飽和二塩基酸ジエステルの製造方法 |
| AU2003211758A1 (en) | 2002-02-28 | 2003-10-08 | Ono Pharmaceutical Co., Ltd. | Process for producing chromone compound |
| DE10217314A1 (de) | 2002-04-18 | 2003-11-13 | Fumapharm Ag Muri | Carbocyclische und Oxacarboncyclische Fumarsäure-Oligomere |
| JP2003315960A (ja) | 2002-04-25 | 2003-11-06 | Konica Minolta Holdings Inc | 銀塩光熱写真ドライイメージング材料 |
| JP4259815B2 (ja) * | 2002-06-06 | 2009-04-30 | ダイセル化学工業株式会社 | 高純度酢酸ブチルの製造方法 |
| EP1913942B1 (en) | 2003-09-09 | 2009-11-11 | Biogen Idec International GmbH | The use of fumaric acid derivatives for inhibition of PGF-induced thymidine uptake of bronchial smooth muscle cells and for inhibition of bronchial smooth cells proliferation |
| JP4163653B2 (ja) | 2004-02-27 | 2008-10-08 | 株式会社日本触媒 | 光学部品用硬化性組成物 |
| WO2007087815A2 (en) | 2004-12-17 | 2007-08-09 | Metanomics Gmbh | Process for the control of production of fine chemicals |
| US7557241B2 (en) | 2004-08-30 | 2009-07-07 | Sanyo Chemical Industries, Ltd. | Method for producing α,β-unsaturated carboxylic acid ester, α,β-unsaturated carboxylic acid ester, and lubricating oil additive |
| PL2316430T3 (pl) | 2004-10-08 | 2012-11-30 | Forward Pharma As | Kompozycje farmaceutyczne o kontrolowanym uwalnianiu, zawierające ester kwasu fumarowego |
| TWI279403B (en) * | 2004-10-20 | 2007-04-21 | Eternal Chemical Co Ltd | Cyclobutanetetracarboxylate compound and preparation method thereof |
| WO2006050730A1 (en) | 2004-11-10 | 2006-05-18 | Aditech Pharma Ab | Novel salts of fumaric acid monoalkylesters and their pharmaceutical use |
| WO2006114900A1 (en) | 2005-04-22 | 2006-11-02 | Canon Kabushiki Kaisha | Magnetic toner |
| DE102005022845A1 (de) | 2005-05-18 | 2006-11-23 | Fumapharm Ag | Thiobernsteinsäurederivate und deren Verwendung |
| US20080227847A1 (en) | 2005-07-07 | 2008-09-18 | Aditech Pharma Ab | Novel Salts of Fumaric Acid Monoalkylesters and Their Pharmaceutical Use |
| WO2007020734A1 (ja) | 2005-08-12 | 2007-02-22 | Lion Corporation | ナノ平滑性とエッチング耐性を有するフォトレジストポリマーならびにレジスト組成物 |
| 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 |
| AU2006344611A1 (en) | 2006-06-16 | 2007-12-21 | Gumlink A/S | Chewing gum comprising a hydrophobic enzyme formulation |
| EP3135282A1 (en) | 2007-02-08 | 2017-03-01 | Biogen MA Inc. | Neuroprotection in demyelinating diseases |
| EP2680009A1 (en) | 2007-02-08 | 2014-01-01 | Biogen Idec MA Inc. | Nrf2 screening assays and related methods and compositions |
| TWI525195B (zh) | 2007-08-10 | 2016-03-11 | 奇諾麥提卡公司 | 合成烯酸及其衍生物之方法 |
| US8729295B2 (en) | 2007-10-26 | 2014-05-20 | The Purolite Company | Controlled catalysis |
| CN101896533B (zh) | 2007-12-12 | 2012-08-22 | 三菱化学株式会社 | 脂肪族聚酯树脂及其制造方法 |
| WO2010079222A1 (en) | 2009-01-09 | 2010-07-15 | Forward Pharma A/S | Pharmaceutical formulation comprising one or more fumaric acid esters in an erosion matrix |
| EP3318249A1 (en) | 2009-04-29 | 2018-05-09 | Biogen MA Inc. | Dimethyl fumarate dosage regimens for the treatment of multiple sclerosis |
| US8338636B2 (en) | 2009-08-07 | 2012-12-25 | Invista North America S.A R.L. | Hydrogenation and esterification to form diesters |
| ME02317B (me) | 2010-02-12 | 2016-06-20 | Biogen Ma Inc | Neuroprotekcija kod demijelinizacijskih bolesti |
| CN102757346A (zh) | 2011-04-26 | 2012-10-31 | 中国科学院兰州化学物理研究所 | 一种富马酸二甲酯的制备方法 |
| KR20140036257A (ko) | 2011-05-26 | 2014-03-25 | 바이오겐 아이덱 엠에이 인코포레이티드 | 다발성 경화증 치료 및 미엘린 함량 보존 및/또는 증가 방법 |
| KR20140035995A (ko) | 2011-06-08 | 2014-03-24 | 바이오겐 아이덱 엠에이 인코포레이티드 | 고순도 및 결정질 다이메틸 푸마레이트의 제조 방법 |
| CN102432464A (zh) | 2011-12-14 | 2012-05-02 | 费近峰 | 一种富马酸二甲酯的连续生产工艺 |
| JP6189333B2 (ja) | 2012-02-07 | 2017-08-30 | バイオジェン エムエー インコーポレーテッド | フマル酸ジメチルを含有する医薬組成物 |
| CN102766050A (zh) | 2012-08-10 | 2012-11-07 | 太仓市运通化工厂 | 一种富马酸二甲酯的合成方法 |
| JP6506174B2 (ja) | 2012-12-21 | 2019-04-24 | バイオジェン エムエー インコーポレイテッド | 重水素置換されたフマル酸誘導体 |
| CN103848739A (zh) | 2014-03-20 | 2014-06-11 | 徐晓宁 | 一种高纯度富马酸二甲酯的生产方法 |
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