CN110520408A - 化合物或中药提取物在制备核酸递送试剂中的应用及其相关产品 - Google Patents
化合物或中药提取物在制备核酸递送试剂中的应用及其相关产品 Download PDFInfo
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- CN110520408A CN110520408A CN201880023083.2A CN201880023083A CN110520408A CN 110520408 A CN110520408 A CN 110520408A CN 201880023083 A CN201880023083 A CN 201880023083A CN 110520408 A CN110520408 A CN 110520408A
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Abstract
本申请涉及从中药中提取多种能够促进核酸递送的化合物或合成的化合物,并利用所提取的化合物或多种组合促进核酸如sRNA吸收和进入靶细胞中,并能促进核酸进入有此需要的对象体内的靶部位。
Description
PCT国内申请,说明书已公开。
Claims (66)
- PCT国内申请,权利要求书已公开。
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CN202211378922.7A CN116082391A (zh) | 2017-03-29 | 2018-03-29 | 化合物或中药提取物在制备核酸递送试剂中的应用及其相关产品 |
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CNPCT/CN2017/078683 | 2017-03-29 | ||
CN2017078683 | 2017-03-29 | ||
PCT/CN2018/081155 WO2018177383A1 (zh) | 2017-03-29 | 2018-03-29 | 化合物或中药提取物在制备核酸递送试剂中的应用及其相关产品 |
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US (2) | US20210108198A1 (zh) |
EP (1) | EP3604269A4 (zh) |
JP (1) | JP7252132B2 (zh) |
KR (1) | KR20200002866A (zh) |
CN (1) | CN110520408B (zh) |
CA (3) | CA3058231A1 (zh) |
MA (1) | MA49023A (zh) |
WO (1) | WO2018177383A1 (zh) |
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CN111918672B (zh) * | 2018-03-29 | 2023-08-08 | 中国医学科学院基础医学研究所 | 人工合成的鞘氨醇衍生物类脂质单体及其递送核酸的用途 |
CN111918858B (zh) * | 2018-03-29 | 2023-03-21 | 中国医学科学院基础医学研究所 | 化合物或中药提取物在制备核酸递送试剂中的应用及其相关产品 |
WO2019184663A1 (zh) * | 2018-03-29 | 2019-10-03 | 中国医学科学院基础医学研究所 | 植物来源"汤剂体"的提取和"本草体"的人工制备及其相关产品 |
WO2020132844A1 (zh) * | 2018-12-25 | 2020-07-02 | 中国医学科学院基础医学研究所 | 炎性相关疾病防治的小rna药物及其组合 |
US20230088528A1 (en) * | 2019-11-08 | 2023-03-23 | Institute Of Basic Medical Sciences Chinese Academy Of Medical Sciences | Use of lipid in preparation of nucleic acid delivery reagent and related product thereof |
CN115671025A (zh) * | 2021-07-27 | 2023-02-03 | 中国医学科学院基础医学研究所 | Fa类脂质化合物在制备核酸递送试剂中的应用及其相关产品 |
WO2024061211A1 (zh) * | 2022-09-20 | 2024-03-28 | 中国医学科学院基础医学研究所 | 用于核酸递送的脂质化合物以及包含所述脂质化合物的相关应用及药物 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008103276A2 (en) * | 2007-02-16 | 2008-08-28 | Merck & Co., Inc. | Compositions and methods for potentiated activity of biologicaly active molecules |
WO2009059201A2 (en) * | 2007-11-02 | 2009-05-07 | The Board Of Regents Of The University Of Texas System | Id2 as a target in colorectal carcinoma |
WO2009129385A1 (en) * | 2008-04-16 | 2009-10-22 | Abbott Laboratories | Cationic lipids and uses thereof |
JP2013245190A (ja) * | 2012-05-25 | 2013-12-09 | Biomedcore Inc | 脂質膜構造体にpH依存性カチオン性を付与する剤、それによりpH依存性カチオン性が付与された脂質膜構造体および脂質膜構造体の製造方法 |
CN106456547A (zh) * | 2014-07-02 | 2017-02-22 | 夏尔人类遗传性治疗公司 | 信使rna的包封 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9308103D0 (en) | 1993-04-20 | 1993-06-02 | Unilever Plc | Cosmetic composition |
AU7574996A (en) | 1995-11-21 | 1997-06-11 | Ilpo Huhtaniemi | Liposomal transfection method |
US6074667A (en) * | 1996-11-20 | 2000-06-13 | Kinnunen; Paavo | Liposomal transfection method |
WO2000030444A1 (en) * | 1998-11-25 | 2000-06-02 | Vanderbilt University | Cationic liposomes for gene transfer |
WO2004096140A2 (en) | 2003-04-25 | 2004-11-11 | The Penn State Research Foundation | Method and system for systemic delivery of growth arresting, lipid-derived bioactive compounds |
CN101939027B (zh) | 2007-10-02 | 2014-07-30 | 玛瑞纳生物技术有限公司 | 用于递送核酸的脂肽 |
WO2009129387A2 (en) * | 2008-04-16 | 2009-10-22 | Abbott Laboratories | Cationic lipids and uses thereof |
WO2009129395A1 (en) * | 2008-04-16 | 2009-10-22 | Abbott Laboratories | Cationic lipids and uses thereof |
GB0910723D0 (en) * | 2009-06-22 | 2009-08-05 | Sylentis Sau | Novel drugs for inhibition of gene expression |
US8877237B2 (en) * | 2010-03-24 | 2014-11-04 | Medesis Pharma | Reverse micelle system comprising nucleic acids and use thereof |
CN102409044B (zh) * | 2010-09-21 | 2014-05-07 | 深圳华大基因科技服务有限公司 | 用于数字基因表达谱的标签及其使用方法 |
KR101306097B1 (ko) | 2010-10-06 | 2013-09-09 | 성균관대학교산학협력단 | 피에이치 민감성 폴리머좀의 제조방법 |
WO2012112730A2 (en) * | 2011-02-15 | 2012-08-23 | Merrimack Pharmaceuticals, Inc. | Compositions and methods for delivering nucleic acid to a cell |
PL3164113T3 (pl) | 2014-06-04 | 2019-09-30 | Exicure, Inc. | Wielowartościowe dostarczanie modulatorów immunologicznych w liposomowych kolistych kwasach nukleinowych do zastosowań profilaktycznych lub terapeutycznych |
CN105078889B (zh) | 2015-07-15 | 2018-10-09 | 魏垒 | 一种用于治疗软骨疾病的脂质体递送***及其制备方法 |
JP7186094B2 (ja) * | 2016-05-06 | 2022-12-08 | イグジキュア オペレーティング カンパニー | インターロイキン17受容体mRNAの特異的ノックダウンのためのアンチセンスオリゴヌクレオチド(ASO)を提示するリポソーム系球状核酸(SNA)構築物 |
-
2018
- 2018-03-29 JP JP2019553884A patent/JP7252132B2/ja active Active
- 2018-03-29 US US16/499,283 patent/US20210108198A1/en active Pending
- 2018-03-29 KR KR1020197031968A patent/KR20200002866A/ko not_active Application Discontinuation
- 2018-03-29 WO PCT/CN2018/081155 patent/WO2018177383A1/zh unknown
- 2018-03-29 CN CN201880023083.2A patent/CN110520408B/zh active Active
- 2018-03-29 MA MA049023A patent/MA49023A/fr unknown
- 2018-03-29 EP EP18775996.4A patent/EP3604269A4/en active Pending
- 2018-03-29 CA CA3058231A patent/CA3058231A1/en active Pending
-
2019
- 2019-03-28 CA CA3095753A patent/CA3095753A1/en active Pending
- 2019-03-29 US US17/042,931 patent/US11974969B2/en active Active
- 2019-03-29 CA CA3095701A patent/CA3095701A1/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008103276A2 (en) * | 2007-02-16 | 2008-08-28 | Merck & Co., Inc. | Compositions and methods for potentiated activity of biologicaly active molecules |
WO2009059201A2 (en) * | 2007-11-02 | 2009-05-07 | The Board Of Regents Of The University Of Texas System | Id2 as a target in colorectal carcinoma |
WO2009129385A1 (en) * | 2008-04-16 | 2009-10-22 | Abbott Laboratories | Cationic lipids and uses thereof |
JP2013245190A (ja) * | 2012-05-25 | 2013-12-09 | Biomedcore Inc | 脂質膜構造体にpH依存性カチオン性を付与する剤、それによりpH依存性カチオン性が付与された脂質膜構造体および脂質膜構造体の製造方法 |
CN106456547A (zh) * | 2014-07-02 | 2017-02-22 | 夏尔人类遗传性治疗公司 | 信使rna的包封 |
Non-Patent Citations (2)
Title |
---|
MARILYN E.FERRARI等: "Synergy between cationic lipid and co-lipid determines the macroscopic structure and transfection activity of lipoplexes", 《SYNERGY BETWEEN CATIONIC LIPID AND CO-LIPID DETERMINES THE MACROSCOPIC STRUCTURE AND TRANSFECTION ACTIVITY OF LIPOPLEXES》 * |
ROSA CHILLEMI等: "Oligonucleotides Conjugated to Natural Lipids:Synthesis of Phosphatidyl-Anchored Antisense Oligonucleotides", 《BIOCONJUGATE CHEMISTR》 * |
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KR20200002866A (ko) | 2020-01-08 |
CA3095753A1 (en) | 2019-10-03 |
CA3095701A1 (en) | 2019-10-03 |
CA3058231A1 (en) | 2018-10-04 |
WO2018177383A9 (zh) | 2019-11-28 |
US11974969B2 (en) | 2024-05-07 |
US20210015767A1 (en) | 2021-01-21 |
US20210108198A1 (en) | 2021-04-15 |
EP3604269A4 (en) | 2021-01-27 |
JP7252132B2 (ja) | 2023-04-04 |
WO2018177383A1 (zh) | 2018-10-04 |
CN110520408B (zh) | 2022-11-25 |
MA49023A (fr) | 2020-02-05 |
EP3604269A1 (en) | 2020-02-05 |
JP2020515616A (ja) | 2020-05-28 |
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