EA035761B1 - Композиция для получения лиофильных форм наночастиц и способ получения лиофильных форм наночастиц - Google Patents
Композиция для получения лиофильных форм наночастиц и способ получения лиофильных форм наночастиц Download PDFInfo
- Publication number
- EA035761B1 EA035761B1 EA201890367A EA201890367A EA035761B1 EA 035761 B1 EA035761 B1 EA 035761B1 EA 201890367 A EA201890367 A EA 201890367A EA 201890367 A EA201890367 A EA 201890367A EA 035761 B1 EA035761 B1 EA 035761B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- cyclodextrin
- composition
- nucleic acid
- dextrin
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 294
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 177
- 238000000034 method Methods 0.000 title claims description 84
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- 150000001875 compounds Chemical class 0.000 claims abstract description 157
- -1 saccharide compound Chemical class 0.000 claims abstract description 104
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 97
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 96
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 96
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- 238000012228 RNA interference-mediated gene silencing Methods 0.000 claims abstract description 9
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- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
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- C—CHEMISTRY; METALLURGY
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- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- Oil, Petroleum & Natural Gas (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| PCT/US2016/043537 WO2017015552A1 (en) | 2015-07-22 | 2016-07-22 | Compositions and methods for nanoparticle lyophile forms |
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| EA201890367A1 EA201890367A1 (ru) | 2018-06-29 |
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| IL288342B2 (en) * | 2015-07-22 | 2024-02-01 | Nitto Denko Corp | Compositions and methods for nanoparticle lyophile forms |
| CA3085694A1 (en) | 2017-12-12 | 2019-06-20 | Lead Biotherapeutics Ltd. | Solid lipid nanoparticle for intracellular release of active substances and method for production the same |
| CN108813619A (zh) * | 2018-07-19 | 2018-11-16 | 广州市汉廷食品有限公司 | 一种无公害食品添加剂及其制备工艺 |
| AU2019347774A1 (en) | 2018-09-28 | 2021-03-25 | Nutcracker Therapeutics, Inc. | Lipid nanoparticle formulations comprising lipidated cationic peptide compounds for nucleic acid delivery |
| EP4365289A3 (en) * | 2018-11-16 | 2024-07-10 | Nitto Denko Corporation | Rna interference delivery formulation and methods for malignant tumors |
| JP7597334B2 (ja) * | 2019-09-26 | 2024-12-10 | 日油株式会社 | 脂質ナノ粒子の凍結乾燥組成物 |
| AU2021228236A1 (en) * | 2020-02-28 | 2022-10-06 | Microcures, Inc. | Fidgetin-like 2 as a target to enhance wound healing |
| WO2021216541A1 (en) * | 2020-04-20 | 2021-10-28 | Board Of Regents, The University Of Texas System | Biologically active dry powder compositions and method of their manufacture and use |
| IL300519A (en) * | 2020-08-14 | 2023-04-01 | Arcturus Therapeutics Inc | Method for lyophilization of lipid nanoparticles |
| WO2022071582A1 (ja) | 2020-10-02 | 2022-04-07 | 国立大学法人北海道大学 | 脂質ナノ粒子 |
| EP4416287A1 (en) | 2021-10-14 | 2024-08-21 | Hemoshear Therapeutics, Inc. | Compositions and methods of treating diseases associated with bile acid transporter |
| KR102712873B1 (ko) * | 2021-12-20 | 2024-10-04 | 고려자연식품(주) | 과일향기 포집을 위한 나노 지질 전달체 제조와 분말화 방법 |
| CN116643056B (zh) * | 2022-02-15 | 2025-02-18 | 厦门万泰凯瑞生物技术有限公司 | 促甲状腺激素受体复合物、试剂盒、制备方法和用途 |
| US20240254485A1 (en) | 2023-01-13 | 2024-08-01 | Hemoshear Therapeutics, Inc. | Sirnas targeting slc10a1 transcripts, compositions and uses thereof |
| WO2025015189A1 (en) * | 2023-07-13 | 2025-01-16 | Comanche Biopharma Corp. | Formulations of nucleic acid compounds and uses thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4537883A (en) * | 1982-11-12 | 1985-08-27 | Mead Johnson & Company | Lyophilized cyclophosphamide |
| US20040121983A1 (en) * | 2002-08-12 | 2004-06-24 | Council Of Scientific And Industrial Research | Method for treating leishmaniasis using methyl-beta-cyclodextrin |
| US20050002998A1 (en) * | 2003-06-04 | 2005-01-06 | Georgetown University | Method for improving stability and shelf-life of liposome complexes |
| US20100278885A1 (en) * | 2007-02-09 | 2010-11-04 | National University Corporation NARA Institute of Science and Technology | C70-Containing Liposome, Method for Producing the Same, and Use of the Same |
| US20110237686A1 (en) * | 2010-03-26 | 2011-09-29 | Cerulean Pharma Inc | Formulations and methods of use |
| US20130115274A1 (en) * | 2011-11-04 | 2013-05-09 | Nitto Denko Corporation | Method of producing lipid nanoparticles for drug delivery |
| US20140288023A1 (en) * | 2002-09-06 | 2014-09-25 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutics delivery |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4537683A (en) | 1982-02-01 | 1985-08-27 | Rohm And Haas Company | Trihalomethane precursor removal using ion exchange emulsions |
| US4927571A (en) | 1987-05-18 | 1990-05-22 | Liposome Technology, Inc. | Preparation of injectable doxorubicin/liposome suspension |
| US20060110441A1 (en) | 2004-10-28 | 2006-05-25 | Harry Wong | Lyophilized liposome formulations and method |
| JP2008520600A (ja) * | 2004-11-19 | 2008-06-19 | ノヴォソム アクチェンゲゼルシャフト | 局所投与のための医薬組成物におけるまたはそれに関する改善 |
| EP2509634B1 (en) * | 2009-12-11 | 2019-03-06 | Pfizer Inc | Stable formulations for lyophilizing therapeutic particles |
| WO2011103150A2 (en) | 2010-02-18 | 2011-08-25 | Cephalon, Inc. | Lyophilized preparations of bendamustine |
| CN102018672B (zh) * | 2010-11-29 | 2013-09-18 | 广州朗圣药业有限公司 | 一种水溶性药物的脂质体冻干组合物及其制备方法 |
| CA3198966A1 (en) | 2011-06-08 | 2012-12-13 | Translate Bio, Inc. | Cleavable lipids |
| US9011903B2 (en) | 2011-06-08 | 2015-04-21 | Nitto Denko Corporation | Cationic lipids for therapeutic agent delivery formulations |
| RU2648753C2 (ru) | 2011-10-21 | 2018-03-28 | Селатор Фармасьютикалз Инк. | Лиофилизированные липосомы |
| EP3673898A1 (en) | 2011-11-04 | 2020-07-01 | Nitto Denko Corporation | Method of producing lipid nanoparticles for drug delivery |
| KR102123129B1 (ko) | 2012-03-28 | 2020-06-15 | 디스커버리 라보라토리스, 인크. | 합성 리포솜 폐 계면활성제의 동결건조 |
| HK1206644A1 (en) * | 2012-03-29 | 2016-01-15 | Shire Human Genetic Therapies, Inc. | Lipid-derived neutral nanoparticles |
| CA2876148C (en) | 2012-06-08 | 2021-01-12 | Nitto Denko Corporation | Lipids for therapeutic agent delivery formulations |
| US20140271815A1 (en) | 2013-03-15 | 2014-09-18 | Aryo Sorayya | Heat-and freeze-stable vaccines and methods of making and using same |
| IL288342B2 (en) * | 2015-07-22 | 2024-02-01 | Nitto Denko Corp | Compositions and methods for nanoparticle lyophile forms |
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2016
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- 2016-07-22 LT LTEP16828602.9T patent/LT3324932T/lt unknown
- 2016-07-22 CN CN201680054543.9A patent/CN108024957B/zh active Active
- 2016-07-22 US US15/217,098 patent/US10300018B2/en active Active
- 2016-07-22 SM SM20210196T patent/SMT202100196T1/it unknown
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2018
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2019
- 2019-04-05 US US16/377,032 patent/US11737982B2/en active Active
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2021
- 2021-03-31 CY CY20211100280T patent/CY1123984T1/el unknown
- 2021-04-22 JP JP2021072339A patent/JP7268079B2/ja active Active
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2023
- 2023-06-30 US US18/346,115 patent/US12311055B2/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4537883A (en) * | 1982-11-12 | 1985-08-27 | Mead Johnson & Company | Lyophilized cyclophosphamide |
| US20040121983A1 (en) * | 2002-08-12 | 2004-06-24 | Council Of Scientific And Industrial Research | Method for treating leishmaniasis using methyl-beta-cyclodextrin |
| US20140288023A1 (en) * | 2002-09-06 | 2014-09-25 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutics delivery |
| US20050002998A1 (en) * | 2003-06-04 | 2005-01-06 | Georgetown University | Method for improving stability and shelf-life of liposome complexes |
| US20100278885A1 (en) * | 2007-02-09 | 2010-11-04 | National University Corporation NARA Institute of Science and Technology | C70-Containing Liposome, Method for Producing the Same, and Use of the Same |
| US20110237686A1 (en) * | 2010-03-26 | 2011-09-29 | Cerulean Pharma Inc | Formulations and methods of use |
| US20130115274A1 (en) * | 2011-11-04 | 2013-05-09 | Nitto Denko Corporation | Method of producing lipid nanoparticles for drug delivery |
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