CN104922141A - 一种用于治疗乙型病毒性肝炎的siRNA组合物 - Google Patents
一种用于治疗乙型病毒性肝炎的siRNA组合物 Download PDFInfo
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- CN104922141A CN104922141A CN201510282415.7A CN201510282415A CN104922141A CN 104922141 A CN104922141 A CN 104922141A CN 201510282415 A CN201510282415 A CN 201510282415A CN 104922141 A CN104922141 A CN 104922141A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims (14)
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510282415.7A CN104922141B (zh) | 2015-05-28 | 2015-05-28 | 一种用于治疗乙型病毒性肝炎的siRNA组合物 |
HK16101640.4A HK1213496A1 (zh) | 2015-05-28 | 2016-02-16 | 種用於治療乙型病毒性肝炎的 組合物 |
PCT/CN2016/083617 WO2016188473A1 (zh) | 2015-05-28 | 2016-05-27 | 一种用于治疗乙型病毒性肝炎的siRNA组合物 |
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2016188473A1 (zh) * | 2015-05-28 | 2016-12-01 | 厦门成坤生物技术有限公司 | 一种用于治疗乙型病毒性肝炎的siRNA组合物 |
CN107827762A (zh) * | 2017-11-14 | 2018-03-23 | 苏州东南药业股份有限公司 | 一种(2, 3‑二油酰基‑丙基)三化甲基氯化铵及其制备方法和用途 |
WO2019105403A1 (zh) * | 2017-12-01 | 2019-06-06 | 苏州瑞博生物技术有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
US11492620B2 (en) | 2017-12-01 | 2022-11-08 | Suzhou Ribo Life Science Co., Ltd. | Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method thereof and use thereof |
US11633482B2 (en) | 2017-12-29 | 2023-04-25 | Suzhou Ribo Life Science Co., Ltd. | Conjugates and preparation and use thereof |
US11660347B2 (en) | 2017-12-01 | 2023-05-30 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate containing same, preparation method, and use thereof |
US11896674B2 (en) | 2018-09-30 | 2024-02-13 | Suzhou Ribo Life Science Co., Ltd. | SiRNA conjugate, preparation method therefor and use thereof |
US11918600B2 (en) | 2018-08-21 | 2024-03-05 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101291653A (zh) * | 2003-07-16 | 2008-10-22 | 普洛体维生物治疗公司 | 脂质包封的干扰rna |
CN102905763A (zh) * | 2009-12-23 | 2013-01-30 | 诺瓦提斯公司 | 脂质、脂质组合物和使用它们的方法 |
CN103189057A (zh) * | 2010-08-26 | 2013-07-03 | 崔坤元 | 大环脂类化合物及其应用 |
CN104107437A (zh) * | 2013-06-09 | 2014-10-22 | 厦门成坤生物技术有限公司 | 一种用于治疗乙型病毒性肝炎的rna干扰组合物及其制备方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010135207A1 (en) * | 2009-05-16 | 2010-11-25 | Agave Pharma, Incorporated | Compositions comprising cationic amphiphiles and colipids for delivering therapeutics molecules |
CN104922141B (zh) * | 2015-05-28 | 2016-05-25 | 厦门成坤生物技术有限公司 | 一种用于治疗乙型病毒性肝炎的siRNA组合物 |
CN104940952B (zh) * | 2015-05-29 | 2016-05-25 | 厦门成坤生物技术有限公司 | 包含大环酯类化合物和siRNA的组合物及其制备方法 |
-
2015
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-
2016
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- 2016-05-27 WO PCT/CN2016/083617 patent/WO2016188473A1/zh active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101291653A (zh) * | 2003-07-16 | 2008-10-22 | 普洛体维生物治疗公司 | 脂质包封的干扰rna |
CN102905763A (zh) * | 2009-12-23 | 2013-01-30 | 诺瓦提斯公司 | 脂质、脂质组合物和使用它们的方法 |
CN103189057A (zh) * | 2010-08-26 | 2013-07-03 | 崔坤元 | 大环脂类化合物及其应用 |
CN104107437A (zh) * | 2013-06-09 | 2014-10-22 | 厦门成坤生物技术有限公司 | 一种用于治疗乙型病毒性肝炎的rna干扰组合物及其制备方法 |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016188473A1 (zh) * | 2015-05-28 | 2016-12-01 | 厦门成坤生物技术有限公司 | 一种用于治疗乙型病毒性肝炎的siRNA组合物 |
CN107827762A (zh) * | 2017-11-14 | 2018-03-23 | 苏州东南药业股份有限公司 | 一种(2, 3‑二油酰基‑丙基)三化甲基氯化铵及其制备方法和用途 |
WO2019105403A1 (zh) * | 2017-12-01 | 2019-06-06 | 苏州瑞博生物技术有限公司 | 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途 |
US11492620B2 (en) | 2017-12-01 | 2022-11-08 | Suzhou Ribo Life Science Co., Ltd. | Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method thereof and use thereof |
US11660347B2 (en) | 2017-12-01 | 2023-05-30 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, composition and conjugate containing same, preparation method, and use thereof |
US11633482B2 (en) | 2017-12-29 | 2023-04-25 | Suzhou Ribo Life Science Co., Ltd. | Conjugates and preparation and use thereof |
US11918600B2 (en) | 2018-08-21 | 2024-03-05 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof |
US11896674B2 (en) | 2018-09-30 | 2024-02-13 | Suzhou Ribo Life Science Co., Ltd. | SiRNA conjugate, preparation method therefor and use thereof |
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HK1213496A1 (zh) | 2016-07-08 |
WO2016188473A1 (zh) | 2016-12-01 |
CN104922141B (zh) | 2016-05-25 |
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