CN113274386A - 氯喹和克立咪唑化合物用于治疗炎症和癌症的用途 - Google Patents
氯喹和克立咪唑化合物用于治疗炎症和癌症的用途 Download PDFInfo
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090312302A1 (en) * | 2008-06-17 | 2009-12-17 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating nonalcoholic fatty liver disease-associated disorders |
| US20100285001A1 (en) * | 2007-10-02 | 2010-11-11 | University Of Rochester | Method and Compositions Related to Synergistic Responses to Oncogenic Mutations |
| CN101903026A (zh) * | 2007-09-18 | 2010-12-01 | 斯坦福大学 | 治疗黄病毒家族病毒感染的方法和治疗黄病毒家族病毒感染的组合物 |
| US20120082659A1 (en) * | 2007-10-02 | 2012-04-05 | Hartmut Land | Methods And Compositions Related To Synergistic Responses To Oncogenic Mutations |
| CN102448458A (zh) * | 2009-03-18 | 2012-05-09 | 小利兰·斯坦福大学理事会 | 治疗黄病毒科病毒感染的方法和组合物 |
| CN102480957A (zh) * | 2009-05-27 | 2012-05-30 | Ptc医疗公司 | 治疗癌症及非肿瘤病症的方法 |
| CN103945695A (zh) * | 2011-09-16 | 2014-07-23 | 卡莱克汀医疗有限公司 | 用于治疗非酒精性脂肪性肝炎和非酒精性脂肪肝病的半乳糖-鼠李糖半乳糖醛酸酯组合物 |
| CN104271574A (zh) * | 2012-02-20 | 2015-01-07 | 武田药品工业株式会社 | 杂环化合物 |
| CN107922404A (zh) * | 2015-06-30 | 2018-04-17 | 艾格集团国际公司 | 氯喹和克立咪唑化合物用于治疗炎症和癌症的用途 |
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| WO1998017231A2 (en) * | 1996-10-18 | 1998-04-30 | Charous B Lauren | Treatment and delivery of hydroxychloroquine |
| EP1175216A2 (en) | 1999-04-30 | 2002-01-30 | APT Pharmaceutical, L.L.C. | Antimalarian agents for the treatment of asthma |
| US20060014786A1 (en) * | 2002-05-17 | 2006-01-19 | Rajeev Raut | Opthalmic pharmaceutical compositions and methods for treating ocular inflammation |
| US20040009949A1 (en) | 2002-06-05 | 2004-01-15 | Coley Pharmaceutical Group, Inc. | Method for treating autoimmune or inflammatory diseases with combinations of inhibitory oligonucleotides and small molecule antagonists of immunostimulatory CpG nucleic acids |
| CN1761478A (zh) * | 2003-02-14 | 2006-04-19 | 康宾纳特克斯公司 | 治疗免疫炎性疾病的联合疗法 |
| TW200902047A (en) | 2003-02-14 | 2009-01-16 | Combinatorx Inc | Methods and reagents for the treatment of diseases and disorders associated with increased levels of proinflammatory cytokines |
| EP1656124A1 (en) * | 2003-03-12 | 2006-05-17 | Cerenis | Methods and compositions for the treatment of cancer |
| TW200522932A (en) | 2003-09-15 | 2005-07-16 | Combinatorx Inc | Methods and reagents for the treatment of diseases and disorders associated with increased levels of proinflammatory cytokines |
| MXPA06004723A (es) * | 2003-10-27 | 2006-07-05 | Vertex Pharma | Combinacion para el tratamiento del hcv. |
| SE0500055D0 (sv) | 2005-01-10 | 2005-01-10 | Astrazeneca Ab | Therapeutic agents 3 |
| RU2468797C2 (ru) * | 2005-06-09 | 2012-12-10 | Биолипокс Аб | Способ и композиция для лечения воспалительных нарушений |
| CN101193622A (zh) | 2005-06-09 | 2008-06-04 | 比奥里波克斯公司 | 治疗炎性疾病的方法和组合物 |
| MX2008010355A (es) * | 2006-02-09 | 2008-10-31 | Schering Corp | Combinaciones que comprenden inhibidores de proteasa del virus de la hepatitis c e inhibidores de polimerasa del virus de la hepatitis c, y metodos de tratamiento relacionados con los mismos. |
| US9101628B2 (en) * | 2007-09-18 | 2015-08-11 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and composition of treating a flaviviridae family viral infection |
| US20120114670A1 (en) | 2007-10-02 | 2012-05-10 | University Of Rochester | Methods and compositions related to synergistic responses to oncogenic mutations |
| CL2009000647A1 (es) * | 2008-04-04 | 2010-06-04 | Chugai Pharmaceutical Co Ltd | Composicion farmaceutica para tratar o prevenir cancer hepatico que comprende una combinacion de un agente quimioterapeutico y un anticuerpo anti-glipicano 3; agente para atenuar un efecto secundario que comprende dicho anticuerpo; metodo para tratar o prevenir un cancer hepatico de un sujeto. |
| DK2460403T3 (da) | 2009-07-31 | 2019-08-19 | Smc Global Asset Inc | Steatohepatitis lever cancer model mus |
| CN103891675B (zh) * | 2009-08-14 | 2016-12-07 | 雷维维科公司 | 用于糖尿病治疗的多转基因猪 |
| WO2011041311A2 (en) | 2009-09-29 | 2011-04-07 | Yale University | Compositions and methods for inhibiting inflammation from and rejection of biomaterials and other methods |
| WO2011051966A2 (en) | 2009-10-12 | 2011-05-05 | Ipca Laboratories Limited | Pharmaceutical compositions for the treatment/prophylaxis of non-alcoholic fatty liver disease |
| US9700560B2 (en) | 2009-11-16 | 2017-07-11 | University Of Georgia Research Foundation, Inc. | 2′-fluoro-6′-methylene carbocyclic nucleosides and methods of treating viral infections |
| US20130273003A1 (en) | 2012-04-17 | 2013-10-17 | Vertex Pharmaceuticals Incorporated | Therapies for Treating Hepatitis C Virus Infection |
| AU2013266393B2 (en) * | 2012-05-22 | 2017-09-28 | Idenix Pharmaceuticals Llc | D-amino acid compounds for liver disease |
| TW201402556A (zh) * | 2012-05-30 | 2014-01-16 | Toyama Chemical Co Ltd | 氘化含氮雜環羧醯胺衍生物或其鹽 |
| WO2014031769A2 (en) * | 2012-08-21 | 2014-02-27 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of diseases associated with inflammation |
| JP6146990B2 (ja) * | 2012-11-16 | 2017-06-14 | コンサート ファーマシューティカルズ インコーポレイテッド | 重水素化されたcftr増強物質 |
| CN103550242B (zh) | 2013-11-22 | 2015-07-15 | 四川国康药业有限公司 | 一种治疗肝纤维化的药物组合物及其制备方法 |
| CN105934438A (zh) | 2013-11-27 | 2016-09-07 | 艾登尼克斯药业有限公司 | 用于治疗肝癌的核苷酸 |
| JP6367545B2 (ja) * | 2013-12-17 | 2018-08-01 | コンサート ファーマシューティカルズ インコーポレイテッド | ルキソリチニブの重水素化誘導体 |
-
2016
- 2016-06-30 AU AU2016288699A patent/AU2016288699B2/en active Active
- 2016-06-30 TW TW112136665A patent/TWI881480B/zh active
- 2016-06-30 EP EP16818845.6A patent/EP3317274A4/en active Pending
- 2016-06-30 CA CA3178499A patent/CA3178499A1/en active Pending
- 2016-06-30 US US15/738,827 patent/US10688083B2/en active Active
- 2016-06-30 CN CN202110651428.2A patent/CN113274386A/zh active Pending
- 2016-06-30 KR KR1020237028986A patent/KR20230129590A/ko not_active Ceased
- 2016-06-30 CA CA2989634A patent/CA2989634C/en active Active
- 2016-06-30 JP JP2017568408A patent/JP7068827B2/ja active Active
- 2016-06-30 TW TW111123545A patent/TWI830262B/zh active
- 2016-06-30 KR KR1020187002620A patent/KR20180032578A/ko not_active Ceased
- 2016-06-30 CN CN201680039155.3A patent/CN107922404B/zh active Active
- 2016-06-30 HK HK18109030.3A patent/HK1249508A1/zh unknown
- 2016-06-30 MX MX2017016681A patent/MX394605B/es unknown
- 2016-06-30 TW TW105120868A patent/TWI771272B/zh active
- 2016-06-30 IL IL300476A patent/IL300476B2/en unknown
- 2016-06-30 IL IL310969A patent/IL310969A/en unknown
- 2016-06-30 NZ NZ776616A patent/NZ776616A/en unknown
- 2016-06-30 WO PCT/US2016/040566 patent/WO2017004454A1/en not_active Ceased
-
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- 2017-12-10 IL IL256233A patent/IL256233A/en active IP Right Grant
- 2017-12-13 ZA ZA2017/08471A patent/ZA201708471B/en unknown
- 2017-12-18 MX MX2022008100A patent/MX2022008100A/es unknown
- 2017-12-18 MX MX2023003792A patent/MX2023003792A/es unknown
-
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- 2020-05-07 US US16/869,312 patent/US12090141B2/en active Active
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-
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- 2021-02-25 AU AU2021201234A patent/AU2021201234A1/en not_active Abandoned
-
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- 2022-05-02 JP JP2022075974A patent/JP7470151B2/ja active Active
-
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- 2023-03-07 AU AU2023201397A patent/AU2023201397B2/en active Active
-
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Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101903026A (zh) * | 2007-09-18 | 2010-12-01 | 斯坦福大学 | 治疗黄病毒家族病毒感染的方法和治疗黄病毒家族病毒感染的组合物 |
| US20100285001A1 (en) * | 2007-10-02 | 2010-11-11 | University Of Rochester | Method and Compositions Related to Synergistic Responses to Oncogenic Mutations |
| US20120082659A1 (en) * | 2007-10-02 | 2012-04-05 | Hartmut Land | Methods And Compositions Related To Synergistic Responses To Oncogenic Mutations |
| US20090312302A1 (en) * | 2008-06-17 | 2009-12-17 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating nonalcoholic fatty liver disease-associated disorders |
| CN102448458A (zh) * | 2009-03-18 | 2012-05-09 | 小利兰·斯坦福大学理事会 | 治疗黄病毒科病毒感染的方法和组合物 |
| CN102480957A (zh) * | 2009-05-27 | 2012-05-30 | Ptc医疗公司 | 治疗癌症及非肿瘤病症的方法 |
| CN103945695A (zh) * | 2011-09-16 | 2014-07-23 | 卡莱克汀医疗有限公司 | 用于治疗非酒精性脂肪性肝炎和非酒精性脂肪肝病的半乳糖-鼠李糖半乳糖醛酸酯组合物 |
| CN104271574A (zh) * | 2012-02-20 | 2015-01-07 | 武田药品工业株式会社 | 杂环化合物 |
| CN107922404A (zh) * | 2015-06-30 | 2018-04-17 | 艾格集团国际公司 | 氯喹和克立咪唑化合物用于治疗炎症和癌症的用途 |
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