CN113993883A - 一种多肽及其应用 - Google Patents
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- CN113993883A CN113993883A CN202080042030.2A CN202080042030A CN113993883A CN 113993883 A CN113993883 A CN 113993883A CN 202080042030 A CN202080042030 A CN 202080042030A CN 113993883 A CN113993883 A CN 113993883A
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Abstract
提供了一种多肽及其应用。该多肽包含由SEQ ID NO:1所示的氨基酸序列中16‑23个连续氨基酸所构成的肽段。该多肽可以改善代谢综合征、减肥、治疗非酒精性脂肪肝病和心血管疾病。
Description
PCT国内申请,说明书已公开。
Claims (8)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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CN201910807205.3A CN112442114A (zh) | 2019-08-29 | 2019-08-29 | 一种多肽及其应用 |
CN2019108072053 | 2019-08-29 | ||
PCT/CN2020/112007 WO2021037187A1 (zh) | 2019-08-29 | 2020-08-28 | 一种多肽及其应用 |
Publications (1)
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CN113993883A true CN113993883A (zh) | 2022-01-28 |
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CN202080042030.2A Pending CN113993883A (zh) | 2019-08-29 | 2020-08-28 | 一种多肽及其应用 |
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US (1) | US20220298209A1 (zh) |
EP (1) | EP4023663A4 (zh) |
CN (2) | CN112442114A (zh) |
WO (1) | WO2021037187A1 (zh) |
Families Citing this family (1)
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CN112442114A (zh) * | 2019-08-29 | 2021-03-05 | 渥太华Hdl药物研发公司 | 一种多肽及其应用 |
Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001057188A2 (en) * | 2000-02-03 | 2001-08-09 | Hyseq, Inc. | Novel nucleic acids and polypeptides |
US20080234192A1 (en) * | 2006-12-08 | 2008-09-25 | Washington, University Of | Compositions and methods of use for treating cardiovascular disease |
CN101721712A (zh) * | 2008-10-21 | 2010-06-09 | 何明磊 | 一种双链聚乙二醇-胰岛素复合物及其制备方法 |
US20120329703A1 (en) * | 2002-05-08 | 2012-12-27 | The Regents Of Te University Of California | Potent and Selective Mediators of Cholesterol Efflux |
US20140336113A1 (en) * | 2011-10-06 | 2014-11-13 | Vanderbilt University | Compositions and methods for treating and preventing hyperlipidemia, fatty liver, atherosclerosis and other disorders associated with metabolic syndrome |
CN105008524A (zh) * | 2012-12-12 | 2015-10-28 | 东安大略研究所儿童医院有限公司 | 用于治疗脑癌的组合物和方法 |
CN107011427A (zh) * | 2017-03-16 | 2017-08-04 | 深圳先进技术研究院 | 调节能量代谢的多肽及其用途 |
CN109200273A (zh) * | 2017-07-04 | 2019-01-15 | 中国药科大学 | 一种多肽用于制备预防或治疗脂肪肝病药物的用途 |
CN109420157A (zh) * | 2017-08-21 | 2019-03-05 | 华中科技大学 | 一种药物组合物的应用 |
AU2018314773A1 (en) * | 2017-08-09 | 2020-03-26 | Sanofi | GLP-1/glucagon receptor agonists in the treatment of fatty liver disease and steatohepatitis |
CN111225680A (zh) * | 2017-10-18 | 2020-06-02 | 上海贺普药业股份有限公司 | 非酒精性脂肪性肝病的治疗药物 |
CN112442114A (zh) * | 2019-08-29 | 2021-03-05 | 渥太华Hdl药物研发公司 | 一种多肽及其应用 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2375771A1 (fr) * | 1999-06-17 | 2000-12-28 | Aventis Pharma S.A. | Acides nucleiques et proteines correspondant au gene abc1 humain |
WO2001032184A2 (en) * | 1999-11-01 | 2001-05-10 | Wisconsin Alumni Research Foundation | Abc1 modulation for the modulation of cholesterol transport |
SG11201609084QA (en) * | 2014-05-02 | 2016-11-29 | Cerenis Therapeutics Holding Sa | Hdl therapy markers |
US10293043B2 (en) * | 2014-06-02 | 2019-05-21 | Armo Biosciences, Inc. | Methods of lowering serum cholesterol |
-
2019
- 2019-08-29 CN CN201910807205.3A patent/CN112442114A/zh active Pending
-
2020
- 2020-08-28 EP EP20855987.2A patent/EP4023663A4/en active Pending
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- 2020-08-28 WO PCT/CN2020/112007 patent/WO2021037187A1/zh unknown
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Patent Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001057188A2 (en) * | 2000-02-03 | 2001-08-09 | Hyseq, Inc. | Novel nucleic acids and polypeptides |
US20120329703A1 (en) * | 2002-05-08 | 2012-12-27 | The Regents Of Te University Of California | Potent and Selective Mediators of Cholesterol Efflux |
US20080234192A1 (en) * | 2006-12-08 | 2008-09-25 | Washington, University Of | Compositions and methods of use for treating cardiovascular disease |
CN101721712A (zh) * | 2008-10-21 | 2010-06-09 | 何明磊 | 一种双链聚乙二醇-胰岛素复合物及其制备方法 |
US20140336113A1 (en) * | 2011-10-06 | 2014-11-13 | Vanderbilt University | Compositions and methods for treating and preventing hyperlipidemia, fatty liver, atherosclerosis and other disorders associated with metabolic syndrome |
CN105008524A (zh) * | 2012-12-12 | 2015-10-28 | 东安大略研究所儿童医院有限公司 | 用于治疗脑癌的组合物和方法 |
CN107011427A (zh) * | 2017-03-16 | 2017-08-04 | 深圳先进技术研究院 | 调节能量代谢的多肽及其用途 |
CN109200273A (zh) * | 2017-07-04 | 2019-01-15 | 中国药科大学 | 一种多肽用于制备预防或治疗脂肪肝病药物的用途 |
AU2018314773A1 (en) * | 2017-08-09 | 2020-03-26 | Sanofi | GLP-1/glucagon receptor agonists in the treatment of fatty liver disease and steatohepatitis |
CN109420157A (zh) * | 2017-08-21 | 2019-03-05 | 华中科技大学 | 一种药物组合物的应用 |
CN111225680A (zh) * | 2017-10-18 | 2020-06-02 | 上海贺普药业股份有限公司 | 非酒精性脂肪性肝病的治疗药物 |
CN112442114A (zh) * | 2019-08-29 | 2021-03-05 | 渥太华Hdl药物研发公司 | 一种多肽及其应用 |
Non-Patent Citations (3)
Title |
---|
M. PILAR VALDECANTOS等: "Differential Effects of a Glucagon-Like Peptide 1 Receptor Agonist in Non-Alcoholic Fatty Liver Disease and in Response to Hepatectomy", 《SCIENTIFIC REPORTS》, vol. 8, no. 16461, pages 1 - 15 * |
张颖玮,王艳侠,石岩等主编: "《肾脏病学现代基础与临床》", 内蒙古科学技术出版社, pages: 339 - 9 * |
梁辰: "16个氨基酸多肽对高脂饮食+CCl4诱导的非酒精性脂肪肝的保护性作用及机制研究", <中国优秀硕士学位论文全文数据库医药卫生科技辑>, pages 064 - 80 * |
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US20220298209A1 (en) | 2022-09-22 |
WO2021037187A1 (zh) | 2021-03-04 |
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