AU2015350151A1 - Compositions and methods for preventing or treating diseases, conditions, or processes characterized by aberrant fibroblast proliferation and extracellular matrix deposition - Google Patents
Compositions and methods for preventing or treating diseases, conditions, or processes characterized by aberrant fibroblast proliferation and extracellular matrix deposition Download PDFInfo
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- AU2015350151A1 AU2015350151A1 AU2015350151A AU2015350151A AU2015350151A1 AU 2015350151 A1 AU2015350151 A1 AU 2015350151A1 AU 2015350151 A AU2015350151 A AU 2015350151A AU 2015350151 A AU2015350151 A AU 2015350151A AU 2015350151 A1 AU2015350151 A1 AU 2015350151A1
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| CN108795935B (zh) * | 2018-05-23 | 2022-06-21 | 中国农业科学院上海兽医研究所(中国动物卫生与流行病学中心上海分中心) | 日本血吸虫SjELAV-like 1基因的siRNA及其应用 |
| CN110575540B (zh) * | 2018-06-07 | 2021-11-02 | 中山大学附属第六医院 | Pdgf抑制剂用于制备治疗肠道炎症疾病的药物方面的用途 |
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| CN113952821A (zh) * | 2021-07-22 | 2022-01-21 | 上海安居乐环保科技股份有限公司 | 一种罐区装卸区废气综合治理方法及系统 |
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| JPH05963A (ja) | 1990-04-13 | 1993-01-08 | Toray Ind Inc | ポリペプチド類組成物 |
| US6331318B1 (en) | 1994-09-30 | 2001-12-18 | Emisphere Technologies Inc. | Carbon-substituted diketopiperazine delivery systems |
| US5352461A (en) | 1992-03-11 | 1994-10-04 | Pharmaceutical Discovery Corporation | Self assembling diketopiperazine drug delivery system |
| US6582728B1 (en) | 1992-07-08 | 2003-06-24 | Inhale Therapeutic Systems, Inc. | Spray drying of macromolecules to produce inhaleable dry powders |
| CA2178729A1 (en) | 1993-12-09 | 1995-06-15 | Eric B. Kmiec | Compounds and methods for site-directed mutations in eukaryotic cells |
| US6428771B1 (en) | 1995-05-15 | 2002-08-06 | Pharmaceutical Discovery Corporation | Method for drug delivery to the pulmonary system |
| ATE321536T1 (de) | 1999-04-05 | 2006-04-15 | Mannkind Corp | Verfahren zur bildung von feinem pulver |
| EP2280004B1 (en) | 1999-06-29 | 2016-04-20 | MannKind Corporation | Pharmaceutical formulations comprising insulin complexed with a diketopiperazine |
| CN101010305B (zh) | 2004-08-20 | 2010-08-11 | 曼金德公司 | 二酮哌嗪合成的催化反应 |
| KR20070057829A (ko) | 2004-08-23 | 2007-06-07 | 맨카인드 코포레이션 | 포스포디에스테라아제 5형의 억제제의 폐 전달 |
| BR122019022692B1 (pt) | 2004-08-23 | 2023-01-10 | Mannkind Corporation | Composição terapêutica em pó seco contendo dicetopiperazina, pelo menos um tipo de cátion e um agente biologicamente ativo |
| KR101384456B1 (ko) | 2005-09-14 | 2014-04-10 | 맨카인드 코포레이션 | 활성제에 대한 결정질 미립자 표면의 친화력의 증가를 기반으로 하는 약물 제제화의 방법 |
| ES2647080T3 (es) | 2006-02-22 | 2017-12-19 | Mannkind Corporation | Un método para mejorar las propiedades farmacéuticas de micropartículas que comprenden dicetopiperazina y un agente activo |
| ES2476842T3 (es) | 2007-01-10 | 2014-07-15 | Purdue Research Foundation | Inhibidores polipept�dicos de HSP27 quinasa y usos de los mismos |
| NL1033850C2 (nl) | 2007-05-15 | 2008-11-18 | 3Force B V | Brandersysteem met voorgemengde branders en vlam-overdrachtsmiddelen. |
| DK2185698T3 (en) | 2007-08-07 | 2015-07-27 | Purdue Research Foundation | Kinase Inhibitors and Uses thereof |
| CA2741302C (en) * | 2008-10-20 | 2017-02-28 | Moerae Matrix, Inc. | Mapkap kinase inhibitor polypeptide for treating or preventing adhesions |
| US9327008B2 (en) * | 2008-12-10 | 2016-05-03 | Purdue Research Foundation | Cell-permeant peptide-based inhibitor of kinases |
| US20110288036A1 (en) * | 2010-05-24 | 2011-11-24 | Cynthia Lander | Methods for Treating or Preventing Vascular Graft Failure |
| CN108014340A (zh) * | 2011-04-12 | 2018-05-11 | 莫伊莱麦屈克斯公司 | 用于预防或治疗以成纤维细胞异常增殖及细胞外基质沉积为特征的疾病的组合物和方法 |
| WO2013134636A1 (en) * | 2012-03-09 | 2013-09-12 | Purdue Research Foundation | Compositions and methods for delivery of kinase inhibiting peptides |
| EP2931272A1 (en) * | 2012-12-12 | 2015-10-21 | The Charlotte-Mecklenburg Hospital Authority D/B/A Carolinas Healthcare System | Methods of treating hepatic fibrosis and associated diseases by regulating rev-erb activity |
-
2015
- 2015-11-17 JP JP2017526674A patent/JP2018501201A/ja active Pending
- 2015-11-17 WO PCT/US2015/061118 patent/WO2016081475A1/en not_active Ceased
- 2015-11-17 CA CA2967621A patent/CA2967621A1/en not_active Abandoned
- 2015-11-17 CN CN201580062363.0A patent/CN107106650A/zh active Pending
- 2015-11-17 MX MX2017006372A patent/MX2017006372A/es unknown
- 2015-11-17 RU RU2017121090A patent/RU2017121090A/ru not_active Application Discontinuation
- 2015-11-17 BR BR112017010238-2A patent/BR112017010238A2/pt not_active Application Discontinuation
- 2015-11-17 KR KR1020177014506A patent/KR20170083063A/ko not_active Withdrawn
- 2015-11-17 EP EP15861651.6A patent/EP3220943A4/en not_active Withdrawn
- 2015-11-17 US US14/943,752 patent/US10500249B2/en not_active Expired - Fee Related
- 2015-11-17 SG SG11201703939XA patent/SG11201703939XA/en unknown
- 2015-11-17 AU AU2015350151A patent/AU2015350151A1/en not_active Abandoned
-
2017
- 2017-05-12 ZA ZA2017/03305A patent/ZA201703305B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2018501201A (ja) | 2018-01-18 |
| US10500249B2 (en) | 2019-12-10 |
| CN107106650A (zh) | 2017-08-29 |
| US20160136234A1 (en) | 2016-05-19 |
| RU2017121090A (ru) | 2018-12-20 |
| BR112017010238A2 (pt) | 2018-02-06 |
| CA2967621A1 (en) | 2016-05-26 |
| WO2016081475A1 (en) | 2016-05-26 |
| MX2017006372A (es) | 2017-08-21 |
| EP3220943A1 (en) | 2017-09-27 |
| EP3220943A4 (en) | 2018-08-01 |
| SG11201703939XA (en) | 2017-06-29 |
| ZA201703305B (en) | 2020-05-27 |
| KR20170083063A (ko) | 2017-07-17 |
| RU2017121090A3 (enExample) | 2019-06-10 |
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