CN1162446C - 促胰岛素分泌肽衍生物 - Google Patents
促胰岛素分泌肽衍生物 Download PDFInfo
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- CN1162446C CN1162446C CNB011128569A CN01112856A CN1162446C CN 1162446 C CN1162446 C CN 1162446C CN B011128569 A CNB011128569 A CN B011128569A CN 01112856 A CN01112856 A CN 01112856A CN 1162446 C CN1162446 C CN 1162446C
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| CNB011128569A CN1162446C (zh) | 2001-05-10 | 2001-05-10 | 促胰岛素分泌肽衍生物 |
| EP02727167A EP1386930A4 (en) | 2001-05-10 | 2002-05-08 | EXENDINDERIVATE |
| KR1020037014451A KR100902208B1 (ko) | 2001-05-10 | 2002-05-08 | 인슐린 친화성 펩티드 유도체 |
| JP2002587464A JP4287153B2 (ja) | 2001-05-10 | 2002-05-08 | インスリン指向性ペプチド誘導体 |
| EP10001237.6A EP2223938B1 (en) | 2001-05-10 | 2002-05-08 | Derivatives of exendin |
| BRPI0209685A BRPI0209685B8 (pt) | 2001-05-10 | 2002-05-08 | derivado de peptídeo insulinotrópico e método para a produção de um derivado de peptídeo insulinotrópico |
| AU2002257497A AU2002257497B2 (en) | 2001-05-10 | 2002-05-08 | Derivatives of exendin |
| PCT/CN2002/000316 WO2002090388A1 (en) | 2001-05-10 | 2002-05-08 | Derivatives of exendin |
| CA2446394A CA2446394C (en) | 2001-05-10 | 2002-05-08 | Insulinotropic peptide derivatives |
| US10/704,409 US7329646B2 (en) | 2001-05-10 | 2003-11-07 | Derivatives of the insulinotropic peptide exendin-4 and methods of production thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101215324B (zh) * | 2007-12-26 | 2010-11-24 | 吉林大学 | 艾塞那肽短肽模拟肽及其在制备糖尿病治疗药物中的应用 |
| CN101040936B (zh) * | 2007-04-28 | 2011-10-19 | 大连水产学院 | 防治鱼类寄生虫病的复方中草药制剂 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6924264B1 (en) * | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| CN1162446C (zh) * | 2001-05-10 | 2004-08-18 | 上海华谊生物技术有限公司 | 促胰岛素分泌肽衍生物 |
| CN100535003C (zh) * | 2004-09-06 | 2009-09-02 | 上海华谊生物技术有限公司 | Exendin 4的类似物 |
| WO2006037811A2 (en) | 2004-10-07 | 2006-04-13 | Novo Nordisk A/S | Protracted exendin-4 compounds |
| US7893017B2 (en) | 2004-10-07 | 2011-02-22 | Novo Nordisk A/S | Protracted GLP-1 compounds |
| CN100429227C (zh) * | 2005-06-29 | 2008-10-29 | 常州制药厂有限公司 | Exendin4多肽片段 |
| CN100374462C (zh) * | 2005-11-21 | 2008-03-12 | 大连帝恩生物工程有限公司 | 截短胰高血糖素样肽1(sGLP-1)、制法及其应用 |
| AU2007267833B2 (en) * | 2006-05-26 | 2012-07-26 | Amylin Pharmaceuticals, Llc | Composition and methods for treatment of congestive heart failure |
| CN102827284B (zh) * | 2006-11-14 | 2015-07-29 | 上海仁会生物制药股份有限公司 | 带有聚乙二醇基团的Exendin或其类似物及其制剂和用途 |
| DK3456340T3 (da) * | 2007-01-08 | 2022-03-21 | Univ Pennsylvania | Glp-1-receptorantagonist til brug ved behandling af medfødt hyperinsulisme |
| RU2413528C2 (ru) | 2007-01-18 | 2011-03-10 | Открытое Акционерное Общество "Валента Фармацевтика" | Лекарственный препарат для лечения сахарного диабета на основе экзенатида и даларгина, применение и способ лечения |
| KR100864584B1 (ko) * | 2008-02-25 | 2008-10-24 | 성균관대학교산학협력단 | 비오틴으로 수식된 엑센딘 유도체, 이의 제조방법 및 이의용도 |
| CN101463078B (zh) * | 2009-01-12 | 2011-07-27 | 华东师范大学 | 一种Exendin-4衍生物及其固相化学合成 |
| CN101665799A (zh) * | 2009-06-29 | 2010-03-10 | 华东师范大学 | 一种Exendin-4衍生物的重组制备方法和应用 |
| WO2011063549A1 (zh) * | 2009-11-26 | 2011-06-03 | Wu Xiaoyan | 长效exendin4的类似物 |
| CN102397558B (zh) * | 2010-09-09 | 2013-08-14 | 中国人民解放军军事医学科学院毒物药物研究所 | Exendin-4类似物的定位聚乙二醇化修饰物及其用途 |
| CN102532301B (zh) * | 2010-12-31 | 2014-09-03 | 上海医药工业研究院 | 一类新型的Exendin-4类似物及其制备方法 |
| CN106928341B (zh) * | 2011-03-30 | 2021-06-01 | 上海仁会生物制药股份有限公司 | 定点单取代聚乙二醇化Exendin类似物及其制备方法 |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| PT2934568T (pt) | 2012-12-21 | 2018-01-04 | Sanofi Sa | Agonistas duplos de glp1/gip ou trigonais de glp1/gip/glucagina |
| HK1219477A1 (zh) | 2013-03-21 | 2017-04-07 | Sanofi-Aventis Deutschland Gmbh | 合成含有乙内酰脲的肽产物 |
| SG11201506885UA (en) | 2013-03-21 | 2015-09-29 | Sanofi Aventis Deutschland | Synthesis of cyclic imide containing peptide products |
| TW201609797A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 雙重ｇｌｐ－１／升糖素受體促效劑 |
| TW201609796A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 非醯化之艾塞那肽－４（ｅｘｅｎｄｉｎ－４）胜肽類似物 |
| TW201609795A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 作為雙重ｇｌｐ－１／ｇｉｐ受體促效劑的艾塞那肽－４（ｅｘｅｎｄｉｎ－４）胜肽類似物 |
| TW201609799A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 雙重ｇｌｐ－１／ｇｉｐ受體促效劑 |
| TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重ｇｌｐ－１／昇糖素受體激動劑之艾塞那肽－４衍生物 |
| TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽－４（Ｅｘｅｎｄｉｎ－４）之肽類雙重ＧＬＰ－１／升糖素受體促效劑 |
| TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自ｅｘｅｎｄｉｎ－４之雙重ｇｌｐ－１／升糖素受體促效劑 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| LT3297653T (lt) | 2015-05-22 | 2022-01-10 | The Board Of Trustees Of The Leland Stanford Junior University | Postbariatrinės hipoglikemijos gydymas glp-1 antagonistais |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| TW201706291A (zh) | 2015-07-10 | 2017-02-16 | 賽諾菲公司 | 作為選擇性肽雙重ｇｌｐ－１／升糖素受體促效劑之新毒蜥外泌肽（ｅｘｅｎｄｉｎ－４）衍生物 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991011457A1 (en) | 1990-01-24 | 1991-08-08 | Buckley Douglas I | Glp-1 analogs useful for diabetes treatment |
| US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
| DK144093D0 (enExample) * | 1993-12-23 | 1993-12-23 | Novo Nordisk As | |
| US6265204B1 (en) * | 1997-01-17 | 2001-07-24 | Genencor International, Inc. | DNA sequences, vectors, and fusion polypeptides for secretion of polypeptides in filamentous fungi |
| NZ504258A (en) * | 1997-11-14 | 2002-12-20 | Amylin Pharmaceuticals Inc | Exendin 3 and 4 agonist compounds for the treatment of diabetes |
| PT1032587E (pt) * | 1997-11-14 | 2008-04-21 | Amylin Pharmaceuticals Inc | Novos compostos agonistas de exendina |
| US6514500B1 (en) | 1999-10-15 | 2003-02-04 | Conjuchem, Inc. | Long lasting synthetic glucagon like peptide {GLP-!} |
| US6329336B1 (en) | 1999-05-17 | 2001-12-11 | Conjuchem, Inc. | Long lasting insulinotropic peptides |
| US6506724B1 (en) | 1999-06-01 | 2003-01-14 | Amylin Pharmaceuticals, Inc. | Use of exendins and agonists thereof for the treatment of gestational diabetes mellitus |
| EP1076066A1 (en) * | 1999-07-12 | 2001-02-14 | Zealand Pharmaceuticals A/S | Peptides for lowering blood glucose levels |
| US6528486B1 (en) | 1999-07-12 | 2003-03-04 | Zealand Pharma A/S | Peptide agonists of GLP-1 activity |
| WO2001041561A1 (en) * | 1999-12-07 | 2001-06-14 | Lee Yong Hwa | A bathtub for a pet dog |
| CN1162446C (zh) * | 2001-05-10 | 2004-08-18 | 上海华谊生物技术有限公司 | 促胰岛素分泌肽衍生物 |
| CN1363654A (zh) | 2001-07-19 | 2002-08-14 | 上海华谊生物技术有限公司 | 生产促胰岛素分泌肽glp－1(7－36)的基因工程菌以及生产glp－1(7－36)的方法 |
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2001
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- 2002-05-08 KR KR1020037014451A patent/KR100902208B1/ko not_active Expired - Lifetime
- 2002-05-08 JP JP2002587464A patent/JP4287153B2/ja not_active Expired - Lifetime
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- 2002-05-08 CA CA2446394A patent/CA2446394C/en not_active Expired - Lifetime
- 2002-05-08 EP EP02727167A patent/EP1386930A4/en not_active Withdrawn
- 2002-05-08 BR BRPI0209685A patent/BRPI0209685B8/pt not_active IP Right Cessation
- 2002-05-08 WO PCT/CN2002/000316 patent/WO2002090388A1/zh not_active Ceased
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101040936B (zh) * | 2007-04-28 | 2011-10-19 | 大连水产学院 | 防治鱼类寄生虫病的复方中草药制剂 |
| CN101215324B (zh) * | 2007-12-26 | 2010-11-24 | 吉林大学 | 艾塞那肽短肽模拟肽及其在制备糖尿病治疗药物中的应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0209685B1 (pt) | 2016-03-01 |
| EP1386930A4 (en) | 2005-09-07 |
| EP1386930A1 (en) | 2004-02-04 |
| CA2446394A1 (en) | 2002-11-14 |
| KR20030094386A (ko) | 2003-12-11 |
| KR100902208B1 (ko) | 2009-06-11 |
| WO2002090388A1 (en) | 2002-11-14 |
| BR0209685A (pt) | 2004-07-13 |
| US7329646B2 (en) | 2008-02-12 |
| JP2005502595A (ja) | 2005-01-27 |
| CN1363559A (zh) | 2002-08-14 |
| EP2223938A1 (en) | 2010-09-01 |
| JP4287153B2 (ja) | 2009-07-01 |
| EP2223938B1 (en) | 2013-07-10 |
| AU2002257497B2 (en) | 2007-10-11 |
| US20040142866A1 (en) | 2004-07-22 |
| BRPI0209685B8 (pt) | 2021-05-25 |
| CA2446394C (en) | 2016-08-16 |
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