RU2549899C2 - Кристаллические формы гидрохлорида финголимода - Google Patents
Кристаллические формы гидрохлорида финголимода Download PDFInfo
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- RU2549899C2 RU2549899C2 RU2011123371/04A RU2011123371A RU2549899C2 RU 2549899 C2 RU2549899 C2 RU 2549899C2 RU 2011123371/04 A RU2011123371/04 A RU 2011123371/04A RU 2011123371 A RU2011123371 A RU 2011123371A RU 2549899 C2 RU2549899 C2 RU 2549899C2
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Cited By (2)
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| RU2627691C1 (ru) * | 2016-07-06 | 2017-08-10 | Олег Ростиславович Михайлов | Кристаллическая η-модификация 2-амино-2-(2-(4-октилфенил)этил)пропан-1,3-диол гидрохлорида, способ её получения и фармацевтическая композиция на её основе |
| RU2663833C2 (ru) * | 2013-03-05 | 2018-08-10 | Биокон Лимитед | Способ получения соединений 2-амино-1,3-пропандиола и их солей |
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| PT2621889T (pt) | 2010-10-01 | 2019-10-30 | Synthon Bv | Processo para produzir cristais de cloridrato de fingolimod |
| MX2013004649A (es) | 2010-10-28 | 2013-06-05 | Mapi Pharma Ltd | Compuestos intermedios y proceso para la preparacion de fingolimod. |
| WO2012071524A1 (en) | 2010-11-24 | 2012-05-31 | Ratiopharm Gmbh | Arylsulfonate salts of fingolimod and processes for preparation thereof |
| EP2646409A4 (en) * | 2010-11-25 | 2015-12-16 | Shilpa Medicare Ltd | FINGOLIMOD POLYMORPHES AND METHOD THEREFOR |
| ES2746016T3 (es) | 2010-12-28 | 2020-03-04 | Synthon Bv | Procedimiento para la preparación de cristales de clorhidrato de fingolimod |
| WO2012097330A2 (en) * | 2011-01-14 | 2012-07-19 | University Of Washington | Compositions and methods for treating degenerative muscle conditions |
| WO2012146980A2 (en) | 2011-04-29 | 2012-11-01 | Dr. Reddy's Laboratories Ltd. | Preparation of fingolimod and its salts |
| CA2886676C (en) | 2011-05-26 | 2019-03-05 | Glycoregimmune, Inc. Carrying On Business As Gri Bio, Inc. | Oxygenated amino- or ammonium-containing sulfonic acid, phosphonic acid and carboxylic acid derivatives and their medical use |
| ES3016961T3 (en) | 2011-05-26 | 2025-05-12 | Gri Bio Inc | Amino- or ammonium-containing sulfonic acid derivatives and their medical use |
| DK2739606T3 (en) | 2011-05-26 | 2016-07-25 | Jado Tech Gmbh | Hydroxy-substituted amino and ammonium derivatives and their medical use |
| EP2739272A1 (en) | 2011-08-01 | 2014-06-11 | Teva Pharmaceutical Industries Ltd. | Process for preparing pharmaceutical compositions comprising fingolimod |
| WO2013091704A1 (en) * | 2011-12-22 | 2013-06-27 | Synthon Bv | Pharmaceutical composition comprising fingolimod |
| CN102887829B (zh) * | 2012-09-05 | 2014-07-02 | 中国科学院上海药物研究所 | 芬戈莫德粘酸盐及其晶体的制备方法和用途 |
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| MX2016001422A (es) * | 2013-07-29 | 2016-10-05 | Aizant Drug Res Solutions Pvt Ltd | Composicion farmaceutica de fingolimod. |
| WO2016042493A1 (en) * | 2014-09-19 | 2016-03-24 | Aizant Drug Research Pvt. Ltd | Pharmaceutical compositions of fingolimod |
| US9925138B2 (en) | 2015-01-20 | 2018-03-27 | Handa Pharmaceuticals, Llc | Stable solid fingolimod dosage forms |
| CN106860440A (zh) * | 2017-01-16 | 2017-06-20 | 南京医科大学第二附属医院 | 盐酸芬戈莫德在制备治疗系统性红斑狼疮脑病药物中的应用 |
| CN106667981B (zh) * | 2017-01-16 | 2019-05-14 | 南京医科大学第二附属医院 | 盐酸芬戈莫德在制备治疗药物性肝损伤药物中的应用 |
| GR1009654B (el) | 2018-08-31 | 2019-11-18 | Φαρματεν Α.Β.Ε.Ε. | Φαρμακευτικο σκευασμα που περιλαμβανει εναν ανοσοτροποποιητικο παραγοντα και μεθοδος για την παρασκευη αυτου |
| WO2020245775A1 (en) * | 2019-06-05 | 2020-12-10 | Biocon Limited | Crystalline forms of 2-amino-2-(2-(4-octylphenyl) ethyl) propane-1,3-diol |
| AU2020372647A1 (en) | 2019-10-31 | 2022-06-16 | Idorsia Pharmaceuticals Ltd | Combination of a CXCR7 antagonist with an S1P1 receptor modulator |
| EP4353709A1 (en) | 2021-05-31 | 2024-04-17 | Shanghai Yonsun Biotechnology Co., Ltd. | Pharmaceutical salt of fingolimod, preparation method therefor, pharmaceutical composition containing same and use thereof |
| EP4212156A1 (en) | 2022-01-13 | 2023-07-19 | Abivax | Combination of 8-chloro-n-(4-(trifluoromethoxy)phenyl)quinolin-2-amine and its derivatives with a s1p receptor modulator |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6476004B1 (en) * | 1996-07-18 | 2002-11-05 | Mitsubishi Pharma Corporation | Pharmaceutical composition |
| WO2003097028A1 (en) * | 2002-05-16 | 2003-11-27 | Novartis Ag | Use of edg receptor binding agents in cancer |
| WO2004089341A1 (en) * | 2003-04-08 | 2004-10-21 | Novartis Ag | Organic compounds |
| WO2007041368A2 (en) * | 2005-09-30 | 2007-04-12 | Novartis Ag | Dpp iv inhibitor for use in the treatment of autoimmune diseases and graft rejection |
| WO2007143081A2 (en) * | 2006-06-02 | 2007-12-13 | The Ohio State University Research Foundation | Therapeutic agents for the treatment of lymphoid malignancies |
| RU2011101771A (ru) * | 2008-06-20 | 2012-07-27 | Новартис АГ (CH) | Педиатрические композиции для лечения рассеянного склероза |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0627406T3 (da) | 1992-10-21 | 1999-07-12 | Taito Co | 2-Amino-1,3-propandiolforbindelser og immunundertrykkende midler |
| JP4079505B2 (ja) * | 1998-04-28 | 2008-04-23 | 田辺三菱製薬株式会社 | ２−アミノ−２−［２−（４−オクチルフェニル）エチル］プロパン−１，３−ジオールの新規な製造法 |
| JP4503184B2 (ja) * | 1998-11-11 | 2010-07-14 | ノヴァルティス アーゲー | ２−アミノ−２−［２−（４−ｃ２−２０−アルキル−フェニル）エチル］プロパン−１，３−ジオール類の製造 |
| PT1031347E (pt) * | 1999-01-27 | 2002-09-30 | Idea Ag | Transporte/imunizacao transnasal com veiculos muitissimo adaptaveis |
| KR100659007B1 (ko) * | 1999-02-10 | 2007-02-28 | 미츠비시 웰파마 가부시키가이샤 | 아미드 화합물 및 그 의약으로서의 용도 |
| CN1144779C (zh) * | 1999-03-11 | 2004-04-07 | 杭州中美华东制药有限公司 | 制备2-[2-(4-烷基苯基)-乙基]-2-氨基-丙二醇的方法以及其中制得的中间产物 |
| NZ529044A (en) * | 2001-06-08 | 2008-03-28 | Novartis Ag | Treatment or prophylaxis of insulin-producing cell graft rejection |
| US20030144712A1 (en) * | 2001-12-20 | 2003-07-31 | Jackson Streeter, M.D. | Methods for overcoming organ transplant rejection |
| GB0217152D0 (en) * | 2002-07-24 | 2002-09-04 | Novartis Ag | Organic compounds |
| CN1212308C (zh) * | 2003-07-24 | 2005-07-27 | 漆又毛 | 2－氨基－2－（2－（4－辛基苯基）乙基）－1，3－丙二醇盐酸盐的制备方法 |
| CN1241903C (zh) * | 2003-10-14 | 2006-02-15 | 马启明 | 制备2－对辛基苯乙基－2－氨基丙二醇的方法 |
| TWI418350B (zh) * | 2005-06-24 | 2013-12-11 | Sankyo Co | 含有ｐｐａｒ調節劑之醫藥組成物的用途 |
| CN1310869C (zh) * | 2005-11-22 | 2007-04-18 | 江苏吴中苏药医药开发有限责任公司 | 2－氨基－2－[2－(4－烷基苯基)乙基]－1,3－丙二醇的制备方法 |
| CN100548968C (zh) * | 2006-03-01 | 2009-10-14 | 徐州师范大学 | 一种制备2-对辛基苯乙基-2-氨基丙二醇盐酸盐的方法 |
| SI3103448T1 (sl) * | 2006-09-26 | 2019-11-29 | Novartis Ag | Farmacevtski sestavek, ki vsebuje modulator S1P |
| PT2621889T (pt) | 2010-10-01 | 2019-10-30 | Synthon Bv | Processo para produzir cristais de cloridrato de fingolimod |
-
2009
- 2009-11-10 PT PT97483507T patent/PT2356090T/pt unknown
- 2009-11-10 CN CN200980144998XA patent/CN102209705A/zh active Pending
- 2009-11-10 RU RU2011123371/04A patent/RU2549899C2/ru active
- 2009-11-10 EP EP09748350.7A patent/EP2356090B1/en active Active
- 2009-11-10 AU AU2009315736A patent/AU2009315736B2/en not_active Ceased
- 2009-11-10 WO PCT/EP2009/064891 patent/WO2010055028A2/en not_active Ceased
- 2009-11-10 JP JP2011535130A patent/JP2012508216A/ja not_active Withdrawn
- 2009-11-10 PL PL09748350T patent/PL2356090T3/pl unknown
- 2009-11-10 MX MX2011004962A patent/MX2011004962A/es active IP Right Grant
- 2009-11-10 CA CA2743232A patent/CA2743232C/en active Active
- 2009-11-10 US US13/128,825 patent/US8530522B2/en not_active Expired - Fee Related
- 2009-11-10 ES ES09748350.7T patent/ES2643161T3/es active Active
- 2009-11-10 BR BRPI0921826A patent/BRPI0921826A2/pt not_active Application Discontinuation
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- 2009-11-10 CN CN201710377640.8A patent/CN107233336A/zh active Pending
- 2009-11-10 RU RU2015111229/04A patent/RU2015111229A/ru not_active Application Discontinuation
- 2009-11-10 KR KR1020137024001A patent/KR20130109254A/ko not_active Withdrawn
-
2013
- 2013-08-12 US US13/964,817 patent/US20140051766A1/en not_active Abandoned
-
2014
- 2014-02-06 JP JP2014020950A patent/JP2014139179A/ja not_active Withdrawn
-
2015
- 2015-09-03 JP JP2015173474A patent/JP2016028056A/ja not_active Withdrawn
-
2017
- 2017-09-07 JP JP2017172276A patent/JP2018035160A/ja active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6476004B1 (en) * | 1996-07-18 | 2002-11-05 | Mitsubishi Pharma Corporation | Pharmaceutical composition |
| WO2003097028A1 (en) * | 2002-05-16 | 2003-11-27 | Novartis Ag | Use of edg receptor binding agents in cancer |
| WO2004089341A1 (en) * | 2003-04-08 | 2004-10-21 | Novartis Ag | Organic compounds |
| WO2007041368A2 (en) * | 2005-09-30 | 2007-04-12 | Novartis Ag | Dpp iv inhibitor for use in the treatment of autoimmune diseases and graft rejection |
| WO2007143081A2 (en) * | 2006-06-02 | 2007-12-13 | The Ohio State University Research Foundation | Therapeutic agents for the treatment of lymphoid malignancies |
| RU2011101771A (ru) * | 2008-06-20 | 2012-07-27 | Новартис АГ (CH) | Педиатрические композиции для лечения рассеянного склероза |
Non-Patent Citations (3)
| Title |
|---|
| & RU2358716. * |
| KIUCHI M; ET AL Synthesis and Immunosuppressive Activity of 2-Substituted 2-Aminopropane-1,3-diols and 2-Aminoethanols , Journal of Medicinal Chemistry, 2000,Vol:43, Page(s):2946 -2961(см.стр. 2946, колонка 1, абзац 1; стр. 2953, колонка 1 последний абзац и колонка 2, первый абзац). * |
| приоритет 20.06.2008.& * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2663833C2 (ru) * | 2013-03-05 | 2018-08-10 | Биокон Лимитед | Способ получения соединений 2-амино-1,3-пропандиола и их солей |
| RU2627691C1 (ru) * | 2016-07-06 | 2017-08-10 | Олег Ростиславович Михайлов | Кристаллическая η-модификация 2-амино-2-(2-(4-октилфенил)этил)пропан-1,3-диол гидрохлорида, способ её получения и фармацевтическая композиция на её основе |
Also Published As
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| KR101393994B1 (ko) | 2014-05-14 |
| RU2011123371A (ru) | 2012-12-20 |
| RU2015111229A3 (enExample) | 2018-11-08 |
| JP2016028056A (ja) | 2016-02-25 |
| AU2009315736B2 (en) | 2013-08-29 |
| US8530522B2 (en) | 2013-09-10 |
| PT2356090T (pt) | 2017-10-16 |
| JP2014139179A (ja) | 2014-07-31 |
| CN102209705A (zh) | 2011-10-05 |
| WO2010055028A3 (en) | 2010-07-08 |
| BRPI0921826A2 (pt) | 2016-01-12 |
| CA2743232A1 (en) | 2010-05-20 |
| US20110229501A1 (en) | 2011-09-22 |
| CN104788325A (zh) | 2015-07-22 |
| CN107233336A (zh) | 2017-10-10 |
| JP2018035160A (ja) | 2018-03-08 |
| AU2009315736A1 (en) | 2010-05-20 |
| PL2356090T3 (pl) | 2017-12-29 |
| EP2356090B1 (en) | 2017-07-05 |
| RU2015111229A (ru) | 2015-11-20 |
| JP2012508216A (ja) | 2012-04-05 |
| CA2743232C (en) | 2015-12-29 |
| ES2643161T3 (es) | 2017-11-21 |
| US20140051766A1 (en) | 2014-02-20 |
| MX2011004962A (es) | 2011-05-30 |
| WO2010055028A2 (en) | 2010-05-20 |
| KR20130109254A (ko) | 2013-10-07 |
| KR20110069156A (ko) | 2011-06-22 |
| EP2356090A2 (en) | 2011-08-17 |
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