TWI836022B - 治療纖維化之方法 - Google Patents
治療纖維化之方法 Download PDFInfo
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- TWI836022B TWI836022B TW109106616A TW109106616A TWI836022B TW I836022 B TWI836022 B TW I836022B TW 109106616 A TW109106616 A TW 109106616A TW 109106616 A TW109106616 A TW 109106616A TW I836022 B TWI836022 B TW I836022B
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| US20250161250A1 (en) * | 2022-02-28 | 2025-05-22 | Nuformix Technologies Limited | Compositions and methods for treatment of idiopathic pulmonary fibrosis |
| CN117618436A (zh) * | 2022-08-25 | 2024-03-01 | 广州再极医药科技有限公司 | 一种稠环嘧啶类化合物的用途 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Family Cites Families (14)
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| GB0427697D0 (en) | 2004-12-17 | 2005-01-19 | Astrazeneca Ab | Chemical process |
| US9844528B2 (en) * | 2006-08-24 | 2017-12-19 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| CN102675282B (zh) * | 2011-03-15 | 2014-12-24 | 广东东阳光药业有限公司 | 取代的喹啉化合物及其使用方法和用途 |
| US20130336889A1 (en) * | 2012-06-14 | 2013-12-19 | National Taiwan University | Nanoparticle and method for detecting or treating a tumor using the same |
| CN105294682B (zh) * | 2014-07-26 | 2017-07-07 | 广东东阳光药业有限公司 | Cdk类小分子抑制剂的化合物及其用途 |
| EP3277282B1 (en) * | 2015-04-01 | 2022-10-12 | Istanbul Universitesi Rektorlugu | Dasatinib for use in the treatment, regression or decelerating the progress of fibrotic lung diseases |
| GB201514760D0 (en) * | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds and method of use |
| JP6905662B2 (ja) * | 2015-11-14 | 2021-07-21 | サンシャイン・レイク・ファーマ・カンパニー・リミテッドＳｕｎｓｈｉｎｅ Ｌａｋｅ Ｐｈａｒｍａ Ｃｏ．，Ｌｔｄ． | 置換キノリン化合物の結晶形およびその医薬組成物 |
| EP3228630A1 (en) * | 2016-04-07 | 2017-10-11 | IMBA-Institut für Molekulare Biotechnologie GmbH | Combination of an apelin antagonist and an angiogenesis inhibitor for the treatment of cancer |
| WO2018026441A1 (en) * | 2016-08-01 | 2018-02-08 | The Regents Of The University Of California | Methods for preventing or treating fibrotic diseases |
| WO2018046876A1 (en) * | 2016-09-06 | 2018-03-15 | The University Of Birmingham | Treatment of chronic inflammatory disease |
| CN106692150B (zh) * | 2016-12-21 | 2019-08-20 | 中国人民解放军第三〇二医院 | 尼达尼布在制备预防和治疗肝纤维化与肝硬化的药物中的用途 |
| EP3964214A1 (en) * | 2020-09-02 | 2022-03-09 | Fraunhofer Gesellschaft zur Förderung der angewandten Forschung e.V. | Modulators of airway basal cells for the treatment or prevention of lung diseases |
-
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016123086A1 (en) * | 2015-01-26 | 2016-08-04 | Yale University | Compositions and methods of using tyrosine kinase inhibitors |
Non-Patent Citations (2)
| Title |
|---|
| 期刊 Rivera-Ortega P, et al, Nintedanib in the management of idiopathic pulmonary fibrosis: clinical trial evidence and real-world experience, Ther Adv Respir Dis, 12:1753466618800618, 2018/09/25 * |
| 期刊 Rivera-Ortega P, et al, Nintedanib in the management of idiopathic pulmonary fibrosis: clinical trial evidence and real-world experience, Ther Adv Respir Dis, 12:1753466618800618, 2018/09/25。 |
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| CN113811296A (zh) | 2021-12-17 |
| PT3930715T (pt) | 2024-08-02 |
| ES2994095T3 (en) | 2025-01-17 |
| MA55076A (fr) | 2022-04-20 |
| DK3930715T3 (da) | 2024-08-05 |
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| HUE067967T2 (hu) | 2024-12-28 |
| JP2024174909A (ja) | 2024-12-17 |
| FI3930715T3 (fi) | 2024-08-05 |
| CN113811296B (zh) | 2025-05-16 |
| EP3930715A1 (en) | 2022-01-05 |
| JP2022521635A (ja) | 2022-04-11 |
| JP7547356B2 (ja) | 2024-09-09 |
| WO2020174420A1 (en) | 2020-09-03 |
| TW202045180A (zh) | 2020-12-16 |
| US20220117966A1 (en) | 2022-04-21 |
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