CN113929761A - 新型生长激素释放激素类似肽改构和二聚体化制备及其应用 - Google Patents
新型生长激素释放激素类似肽改构和二聚体化制备及其应用 Download PDFInfo
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CN113398091A (zh) * | 2021-08-02 | 2021-09-17 | 重庆铜梁玉媛医院股份有限公司 | 一种治疗不孕不育症的胶囊制剂及其制备方法 |
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US20090023646A1 (en) * | 2002-09-18 | 2009-01-22 | Centre Hospitalier De L'universite De Montreal (Chum) | GHRH analogues |
CN104558150A (zh) * | 2014-11-04 | 2015-04-29 | 广东药学院 | 一类新型生长激素释放激素类似肽及其在制备治疗不孕不育药物中的应用 |
CN109180800A (zh) * | 2018-08-01 | 2019-01-11 | 广东药科大学 | 新型生长激素释放激素类似肽二聚体及其应用 |
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US20090088380A1 (en) * | 2007-07-12 | 2009-04-02 | Pierrette Gaudreau | Ghrh analogs and therapeutic uses thereof |
WO2009108364A2 (en) * | 2008-02-27 | 2009-09-03 | Ipsen Pharma S.A.S. | Antagonistic analogues of ghrh |
CN112898406B (zh) * | 2019-10-12 | 2023-11-10 | 深圳纳福生物医药有限公司 | 不同构型的glp-1类似肽修饰二聚体及其制备方法在治疗ii型糖尿病中的应用 |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090023646A1 (en) * | 2002-09-18 | 2009-01-22 | Centre Hospitalier De L'universite De Montreal (Chum) | GHRH analogues |
CN104558150A (zh) * | 2014-11-04 | 2015-04-29 | 广东药学院 | 一类新型生长激素释放激素类似肽及其在制备治疗不孕不育药物中的应用 |
CN109180800A (zh) * | 2018-08-01 | 2019-01-11 | 广东药科大学 | 新型生长激素释放激素类似肽二聚体及其应用 |
Non-Patent Citations (2)
Title |
---|
CAMPBELL RM 等: "Rational design, synthesis, and biological evaluation of novel growth hormone releasing factor analogues", BIOPOLYMERS, vol. 37, pages 67 - 88, XP008007073, DOI: 10.1002/bip.360370204 * |
张旭东 等: "中华地鼠雌性不孕症模型的建立及其评价", 广东医学, pages 12 - 15 * |
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CN117229384A (zh) * | 2023-07-12 | 2023-12-15 | 广东药科大学 | 新型生长激素释放激素类似肽单体、二聚体或四聚体及其制备和应用 |
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