CA3046669A1 - Method for preventing and treating skin fibrosis - Google Patents
Method for preventing and treating skin fibrosis Download PDFInfo
- Publication number
- CA3046669A1 CA3046669A1 CA3046669A CA3046669A CA3046669A1 CA 3046669 A1 CA3046669 A1 CA 3046669A1 CA 3046669 A CA3046669 A CA 3046669A CA 3046669 A CA3046669 A CA 3046669A CA 3046669 A1 CA3046669 A1 CA 3046669A1
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- Prior art keywords
- plasminogen
- drug
- fibrosis
- mice
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| CNPCT/CN2016/110174 | 2016-12-15 | ||
| CN2016110174 | 2016-12-15 | ||
| PCT/CN2017/089054 WO2018107694A1 (zh) | 2016-12-15 | 2017-06-19 | 一种预防和治疗皮肤纤维化的方法 |
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| CA3046669A1 true CA3046669A1 (en) | 2018-06-21 |
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| CA3047174A Abandoned CA3047174A1 (en) | 2016-12-15 | 2017-06-19 | Method for preventing and treating liver fibrosis |
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| CA3047174A Abandoned CA3047174A1 (en) | 2016-12-15 | 2017-06-19 | Method for preventing and treating liver fibrosis |
| CA3046671A Active CA3046671C (en) | 2016-12-15 | 2017-06-19 | Method for preventing and treating pulmonary fibrosis |
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| EP3556380A4 (en) | 2016-12-15 | 2020-05-13 | Talengen International Limited | METHOD FOR PREVENTING AND TREATING FABRIC OF TISSUE AND ORGAN |
| ES3036897T3 (en) | 2017-06-19 | 2025-09-25 | Talengen Int Ltd | Plasminogen for use in treating parkinson's and alzheimer's disease |
| TWI868051B (zh) * | 2017-06-23 | 2025-01-01 | 美商波麥堤克生物治療股份有限公司 | 與pai-1過表現相關之病狀的纖維蛋白溶酶原治療 |
| TWI788779B (zh) * | 2020-02-11 | 2023-01-01 | 大陸商深圳瑞健生命科學研究院有限公司 | 一種治療病毒性肺炎的方法和藥物 |
| CN114984032B (zh) * | 2022-06-27 | 2023-07-07 | 四川大学 | Dna四面体框架核酸-绿原酸复合物及其在制备治疗肝纤维化的药物中的用途 |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| US4645668A (en) | 1983-08-04 | 1987-02-24 | Biospecifics, Nv | Method for the prevention and treatment of scars with enzymes |
| GB8721951D0 (en) | 1987-09-18 | 1987-10-28 | Thrombosis Research Trust | Organic compounds |
| MX9800684A (es) | 1995-07-27 | 1998-04-30 | Genentech Inc | Formulacion de proteinas liofilizadas isotonicas estables. |
| EP0910571B1 (en) | 1996-05-03 | 2005-07-20 | Abbott Laboratories | Novel antiangiogenic peptides, polynucleotides encoding same and methods for inhibiting angiogenesis |
| CA2295925A1 (en) | 1997-06-26 | 1999-01-07 | Karolinska Innovations Ab | Kringle domains 1-5 of plasminogen, capable of modulating angiogenesis in vivo |
| WO2000010506A2 (en) | 1998-08-20 | 2000-03-02 | University Of Vermont And State Agriculture College | Angiogenesis inhibitors and uses thereof |
| US7763580B2 (en) | 1999-01-05 | 2010-07-27 | University Of Utah Research Foundation | Methods for treating conditions associated with the accumulation of excess extracellular matrix |
| AU2002239414A1 (en) | 2000-11-02 | 2002-05-27 | Bristol-Myers Squibb Company | Modified plasminogen related peptide fragments and their use as angiogenesis inhibitors |
| MXPA00011713A (es) | 2000-11-28 | 2002-05-31 | Tgt Lab S A De C V | Vectores recombinantes virales y no virales conteniendo el gen humano del activador de plasminogeno derivado de urocinasa y su utilidad en el tratamiento de diversos tipos de fibrosis hepatica, renal, pulmonar, pancreatica, cardiaca y cicatrices hipe |
| US7067492B2 (en) | 2001-09-06 | 2006-06-27 | Omnio Ab | Method of promoting healing of a tympanic membrane perforation |
| US20050124036A1 (en) | 2002-02-06 | 2005-06-09 | Rudy Susilo | Method for producing recombinant proteins in micro-organisms |
| MXPA04007585A (es) * | 2002-02-06 | 2005-09-20 | N Zyme Biotec Gmbh | Metodo para la produccion de proteinas recombinantes en microorganismos. |
| US20040043026A1 (en) | 2002-05-13 | 2004-03-04 | Tai-Lan Tuan | Treatment and prevention of abnormal scar formation in keloids and other cutaneous or internal wounds or lesions |
| CA2509170A1 (en) | 2002-12-10 | 2004-06-24 | Wyeth | Substituted 3-alkyl and 3-arylalkyl 1h-indol-1-yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (pai-1) |
| US20050250694A1 (en) | 2003-10-10 | 2005-11-10 | Ma Jian-Xing | Compounds useful in inhibiting vascular leakage, inflammation and fibrosis and methods of making and using same |
| AU2005277137A1 (en) | 2004-08-23 | 2006-03-02 | Wyeth | Pyrrolo-naphthyl acids as PAI-1 inhibitors |
| CN101573134B (zh) * | 2006-08-28 | 2013-03-06 | 李季男 | 抗感染候选药物 |
| US20100080773A1 (en) | 2008-09-26 | 2010-04-01 | Sdg, Inc. | Orally Bioavailable Lipid-Based Constructs |
| MX2010005947A (es) | 2007-11-29 | 2010-09-10 | Talecris Biotherapeutics Inc | Plasmina modificada de forma recombinante. |
| WO2009111625A2 (en) * | 2008-03-05 | 2009-09-11 | Board Of Regents, The University Of Texas System | Peptide inhibition of lung epithelial apoptosis and pulmonary fibrosis |
| NZ597452A (en) * | 2009-07-10 | 2013-10-25 | Thrombogenics Nv | Variants of plasminogen and plasmin |
| CN101628113B (zh) | 2009-08-18 | 2012-01-04 | 南京农业大学 | 蚯蚓纤溶酶抗肝纤维化的应用 |
| NZ600160A (en) | 2009-11-07 | 2014-05-30 | Astute Medical Inc | Methods and compositions for diagnosis and prognosis of renal injury and renal failure |
| US20120114652A1 (en) | 2010-05-03 | 2012-05-10 | Abbott Laboratories | Anti-pai-1 antibodies and methods of use thereof |
| CN102121023B (zh) | 2010-12-22 | 2012-07-04 | 中山大学 | 突变型人纤溶酶原kringle5及其制备方法及应用 |
| RU2604807C2 (ru) * | 2011-01-05 | 2016-12-10 | ТромбоДженикс НВ | Варианты плазминогена и плазмина |
| CN102154253A (zh) | 2011-01-06 | 2011-08-17 | 郑州大学 | 具有抑制血小板凝集功能的微小纤溶酶原突变体及其制备方法和用途 |
| US9655973B2 (en) | 2012-03-09 | 2017-05-23 | Vascular Biosciences | Orally active, cell-penetrating homing peptide and methods of using same |
| KR101467109B1 (ko) | 2013-07-10 | 2014-12-01 | 영남대학교 산학협력단 | Ｂｉｘ02189 화합물을 유효성분으로 포함하는 폐섬유증 예방 또는 치료용 조성물 |
| TW201722994A (zh) | 2013-08-13 | 2017-07-01 | 賽諾菲公司 | 胞漿素原活化素抑制劑-１（ｐａｉ-１）之抗體及其用途 |
| EA033403B1 (ru) | 2013-08-13 | 2019-10-31 | Sanofi Sa | Антитела к ингибитору активатора плазминогена 1 (pai-1) и пути их применения |
| CN104371019B (zh) | 2013-08-13 | 2019-09-10 | 鸿运华宁（杭州）生物医药有限公司 | 一种能与glp-1r特异性结合的抗体及其与glp-1的融合蛋白质 |
| WO2015026494A2 (en) | 2013-08-20 | 2015-02-26 | Trustees Of Dartmouth College | Methods for treating tissue fibrosis |
| TR201907379T4 (tr) * | 2014-02-21 | 2019-06-21 | Astellas Pharma Inc | Yeni anti-insan PAI-1 antikoru. |
| HUE068351T2 (hu) | 2014-12-19 | 2024-12-28 | Kedrion Biopharma Inc | Plazminogént tartalmazó gyógyszerkészítmény és annak felhasználásai |
| TWI801331B (zh) | 2015-11-03 | 2023-05-11 | 美商波麥堤克生物治療股份有限公司 | 纖維蛋白溶酶原缺乏症之纖維蛋白溶酶原替代療法 |
| CN109069567A (zh) | 2015-12-18 | 2018-12-21 | 泰伦基国际有限公司 | 一种预防或治疗糖尿病性神经损伤及其相关病症的方法 |
| EP3391902B1 (en) | 2015-12-18 | 2023-10-18 | Talengen International Limited | Plasminogen for use in the treatment of diabetic angiocardiopathy |
| CN106890318A (zh) | 2015-12-18 | 2017-06-27 | 深圳瑞健生命科学研究院有限公司 | 一种预防和治疗糖尿病性心脏病的新方法 |
| CN106890320A (zh) | 2015-12-18 | 2017-06-27 | 深圳瑞健生命科学研究院有限公司 | 一种用于预防或治疗急性及慢性血栓的方法 |
| CN108463236A (zh) | 2015-12-18 | 2018-08-28 | 泰伦基国际有限公司 | 一种预防或治疗放射性和化学性损伤的方法 |
| CN106890324A (zh) | 2015-12-18 | 2017-06-27 | 深圳瑞健生命科学研究院有限公司 | 一种预防和治疗糖尿病肾病的方法 |
| CN115845037A (zh) | 2015-12-18 | 2023-03-28 | 泰伦基国际有限公司 | 一种用于预防或治疗急性及慢性血栓的方法 |
| US11389515B2 (en) | 2016-12-15 | 2022-07-19 | Talengen International Limited | Method for mitigating heart disease |
| EP3556380A4 (en) | 2016-12-15 | 2020-05-13 | Talengen International Limited | METHOD FOR PREVENTING AND TREATING FABRIC OF TISSUE AND ORGAN |
| WO2018108161A1 (zh) | 2016-12-15 | 2018-06-21 | 深圳瑞健生命科学研究院有限公司 | 一种预防和治疗肥胖症的方法和药物 |
| CA3047170A1 (en) | 2016-12-15 | 2018-06-21 | Talengen International Limited | Method for preventing and treating drug-induced renal injury |
| TWI763680B (zh) | 2016-12-15 | 2022-05-11 | 大陸商深圳瑞健生命科學硏究院有限公司 | 纖溶酶原在製備藥物中的用途 |
| TW201822809A (zh) | 2016-12-15 | 2018-07-01 | 深圳瑞健生命科學硏究院有限公司 | 一種預防和治療高脂血症的方法 |
| ES3036897T3 (en) | 2017-06-19 | 2025-09-25 | Talengen Int Ltd | Plasminogen for use in treating parkinson's and alzheimer's disease |
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- 2017-06-19 EP EP17882248.2A patent/EP3556395A4/en active Pending
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- 2017-06-19 US US16/470,179 patent/US11154595B2/en active Active
- 2017-06-19 TW TW110101502A patent/TW202123955A/zh unknown
- 2017-06-19 CN CN201780078169.0A patent/CN110191718A/zh active Pending
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