RU2621129C2 - Композиция и способ лечения аутоиммунного заболевания - Google Patents
Композиция и способ лечения аутоиммунного заболевания Download PDFInfo
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- RU2621129C2 RU2621129C2 RU2014115807A RU2014115807A RU2621129C2 RU 2621129 C2 RU2621129 C2 RU 2621129C2 RU 2014115807 A RU2014115807 A RU 2014115807A RU 2014115807 A RU2014115807 A RU 2014115807A RU 2621129 C2 RU2621129 C2 RU 2621129C2
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| BR112022026615A2 (pt) * | 2020-06-30 | 2023-01-24 | Redhill Biopharma Ltd | Produtos combinados em dose tripla fixa de antibióticos, regime de dosagem, métodos e kits para tratamento de infecções por micobactérias pulmonares não tuberculosas |
| WO2023182288A1 (ja) * | 2022-03-22 | 2023-09-28 | 国立大学法人京都大学 | シャルコー・マリー・ツース病の治療または予防薬 |
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|---|---|---|---|---|
| WO1998043667A1 (en) * | 1997-04-01 | 1998-10-08 | Borody Thomas J | Methods and compositions for treating inflammatory bowel disease |
| US20110059136A1 (en) * | 2008-02-08 | 2011-03-10 | Thomas Julius Borody | Methods and Compositions for Treating Inflammatory Bowel Disease |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7488580B1 (en) | 2005-03-10 | 2009-02-10 | University Of Central Florida Research Foundation, Inc. | Protocol for detection of Mycobacterium avium subspecies paratuberculosis in blood |
| US20090054380A1 (en) * | 2005-12-20 | 2009-02-26 | Greenstein Robert J | Methods for diagnosing and treating a mycobacterium avium subspecies paratuberculosis infection |
| US20080275063A1 (en) * | 2007-04-24 | 2008-11-06 | Heike Schauerte | Inhibitors of protein kinases |
| EP2200613B1 (en) * | 2007-09-21 | 2018-09-05 | The Johns Hopkins University | Phenazine derivatives and uses thereof |
| US20120237472A1 (en) * | 2009-07-24 | 2012-09-20 | The Johns Hopkins University | Methods and compositions for treating or preventing autoimmune diseases using immunomodulatory agents |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998043667A1 (en) * | 1997-04-01 | 1998-10-08 | Borody Thomas J | Methods and compositions for treating inflammatory bowel disease |
| US20110059136A1 (en) * | 2008-02-08 | 2011-03-10 | Thomas Julius Borody | Methods and Compositions for Treating Inflammatory Bowel Disease |
Non-Patent Citations (4)
| Title |
|---|
| Yunzhao R. Ren et al. Clofazimine inhibits human Kv1.3 potassium channel by perturbing calcium oscillation in T lymphocytes. PLoS ONE, vol. 3, issue 12, декабрь 2008. WARWICK SELBY et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin and clofazimine for Crohn's disease, GASTROENTEROLOGY 2007; 132:2313-2319. * |
| Киркин Б.В. Новое в изучении болезни Крона. "РМЖ"; N 3 от 03.08.1996. Paola Caramaschi et al. Liver imprairment after concomitant administration of bosentan and clarithromycin in systemic sclerosis., Elsever Masson SAS, 16.04.2009 * |
| Киркин Б.В. Новое в изучении болезни Крона. "РМЖ"; N 3 от 03.08.1996. Paola Caramaschi et al. Liver imprairment after concomitant administration of bosentan and clarithromycin in systemic sclerosis., Elsever Masson SAS, 16.04.2009. Yunzhao R. Ren et al. Clofazimine inhibits human Kv1.3 potassium channel by perturbing calcium oscillation in T lymphocytes. PLoS ONE, vol. 3, issue 12, декабрь 2008. WARWICK SELBY et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin and clofazimine for Crohn's disease, GASTROENTEROLOGY 2007; 132:2313-2319. * |
| Царегородцева Т.М. и др. Цитокины при заболевании органов пищеварения. найдено из интернета (29.09.2016) URL: [http://www.rlsnet.ru/articles_426.htm], 28.04.2009. * |
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