RU2717677C1 - Налмефен, налтрексон или их производные для применения в лечении (не)алкогольного стеатогепатита или неалкогольной жировой болезни печени - Google Patents
Налмефен, налтрексон или их производные для применения в лечении (не)алкогольного стеатогепатита или неалкогольной жировой болезни печени Download PDFInfo
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| EP3712254A1 (en) | 2014-05-28 | 2020-09-23 | Children's Hospital Medical Center | Methods and systems for converting precursor cells into gastric tissues through directed differentiation |
| EP3207123A1 (en) | 2014-10-17 | 2017-08-23 | Children's Hospital Center D/b/a Cincinnati Children's Hospital Medical Center | In vivo model of human small intestine using pluripotent stem cells and methods of making and using same |
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| EP3534919A4 (en) | 2016-11-04 | 2020-11-11 | Children's Hospital Medical Center | Liver organoid compositions and methods of making and using same |
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|---|---|---|---|---|
| RU2090190C1 (ru) * | 1990-06-04 | 1997-09-20 | Алко Лтд, Орион-Ихтюмя Ой | Способ лечения алкоголизма |
| US20090169508A1 (en) * | 2003-05-16 | 2009-07-02 | Jenkin Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| CN102048733A (zh) * | 2010-12-23 | 2011-05-11 | 武汉同源药业有限公司 | 盐酸纳美芬的医药用途 |
| RU2561871C2 (ru) * | 2010-03-31 | 2015-09-10 | Ак Кимя Итхалат-Ихрацат Ве Санайии А.С. | Антагонист опиоидных рецепторов (налтрексон) для использования в терапии герпесного опоясывающего лишая |
| US20150335638A1 (en) * | 2009-07-16 | 2015-11-26 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7923454B2 (en) | 2002-05-17 | 2011-04-12 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| CN103405431B (zh) | 2002-05-17 | 2016-04-13 | 台湾J药品有限公司 | 阿片和阿片样化合物及其用途 |
| MA38385A1 (fr) * | 2013-04-22 | 2017-09-29 | Cadila Healthcare Ltd | Nouvelle composition pour la stéatose hépatique non alcoolique (nafld) |
| EP3939570A1 (en) * | 2016-02-18 | 2022-01-19 | Immune Therapeutics, Inc. | Naltrexone for treating or preventing autoimmune and inflammatory diseases |
-
2017
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- 2017-04-20 CA CA3021788A patent/CA3021788C/en active Active
- 2017-04-20 AU AU2017253228A patent/AU2017253228B2/en active Active
- 2017-04-20 WO PCT/US2017/028529 patent/WO2017184819A1/en not_active Ceased
- 2017-04-20 BR BR112018071705-3A patent/BR112018071705A2/pt not_active IP Right Cessation
- 2017-04-20 RU RU2018136387A patent/RU2717677C1/ru active
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- 2017-04-20 JP JP2018554716A patent/JP2019514872A/ja active Pending
- 2017-04-20 CN CN202311054107.XA patent/CN117137917A/zh active Pending
- 2017-04-20 EP EP17721252.9A patent/EP3445363A1/en not_active Ceased
- 2017-04-20 KR KR1020187031996A patent/KR20180129909A/ko not_active Ceased
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2090190C1 (ru) * | 1990-06-04 | 1997-09-20 | Алко Лтд, Орион-Ихтюмя Ой | Способ лечения алкоголизма |
| US20090169508A1 (en) * | 2003-05-16 | 2009-07-02 | Jenkin Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US20150335638A1 (en) * | 2009-07-16 | 2015-11-26 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| RU2561871C2 (ru) * | 2010-03-31 | 2015-09-10 | Ак Кимя Итхалат-Ихрацат Ве Санайии А.С. | Антагонист опиоидных рецепторов (налтрексон) для использования в терапии герпесного опоясывающего лишая |
| CN102048733A (zh) * | 2010-12-23 | 2011-05-11 | 武汉同源药业有限公司 | 盐酸纳美芬的医药用途 |
Non-Patent Citations (1)
| Title |
|---|
| A. MOSLEHI et al. ACTA PHYSIOLOGICA HUNGARICA, vol.101. no.3, 2014, pp. 341-352. GIOVANNI ADDOLORATO et al. CNS DRUGS, vol.27, no.4, 2013, pp. 287-299. * |
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| AU2017253228A1 (en) | 2018-09-27 |
| KR20180129909A (ko) | 2018-12-05 |
| EP3445363A1 (en) | 2019-02-27 |
| CA3021788C (en) | 2021-08-03 |
| AU2017253228A8 (en) | 2019-01-17 |
| JP2019514872A (ja) | 2019-06-06 |
| US20170304294A1 (en) | 2017-10-26 |
| WO2017184819A1 (en) | 2017-10-26 |
| AU2017253228B2 (en) | 2020-04-09 |
| BR112018071705A2 (pt) | 2019-02-19 |
| CA3021788A1 (en) | 2017-10-26 |
| US10045977B2 (en) | 2018-08-14 |
| CN109069503A (zh) | 2018-12-21 |
| CN117137917A (zh) | 2023-12-01 |
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