BR0012624A - Métodos para a preparação de agentes terapêuticos envolvidos por lipìdeos - Google Patents

Métodos para a preparação de agentes terapêuticos envolvidos por lipìdeos

Info

Publication number
BR0012624A
BR0012624A BR0012624-1A BR0012624A BR0012624A BR 0012624 A BR0012624 A BR 0012624A BR 0012624 A BR0012624 A BR 0012624A BR 0012624 A BR0012624 A BR 0012624A
Authority
BR
Brazil
Prior art keywords
lipid
therapeutic agent
vesicles
preformed
destabilizing
Prior art date
Application number
BR0012624-1A
Other languages
English (en)
Other versions
BR0012624B1 (pt
Inventor
Norbert Maurer
Kim F Wong
Pieter R Cullis
Original Assignee
Inex Pharmaceuticals Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Inex Pharmaceuticals Corp filed Critical Inex Pharmaceuticals Corp
Publication of BR0012624A publication Critical patent/BR0012624A/pt
Publication of BR0012624B1 publication Critical patent/BR0012624B1/pt

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/127Liposomes
    • A61K9/1277Processes for preparing; Proliposomes
    • A61K9/1278Post-loading, e.g. by ion or pH gradient
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/127Liposomes
    • A61K9/1271Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A61K9/1272Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/127Liposomes
    • A61K9/1277Processes for preparing; Proliposomes

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dispersion Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Manufacturing Of Micro-Capsules (AREA)

Abstract

"MéTODOS PARA A PREPARAçãO DE AGENTES TERAPêUTICOS ENVOLVIDOS POR LIPìDEOS". Partículas de um agente terapêutico completamente envolvidas por lipídeos de um agente terapêutico carregado são preparadas através da combinação de uma composição de lipídeos contendo vesículas de lipídeos previamente formadas, um agente terapêutico carregado, e um agente desestabilizante para formar uma mistura de vesículas previamente formadas e agente terapêutico num solvente desestabilizante. O solvente desestabilizante é eficaz para desestabilizar a membrana das vesículas de lipídeos previamente formadas sem romper as vesículas. A mistura resultante é incubada por um período de tempo suficiente para permitir o encapsulamento do agente terapêutico dentro das vesículas de lipídeos previamente formadas. O agente desestabilizante é então removido para produzir partículas de um agente terapêutico completamente envolvidas por lipídeos. As vesículas de lipídeos previamente formadas compreendem um lipídeo carregado que apresenta uma carga que é oposta à carga do agente terapêutico carregado e um lipídeo modificado apresentando uma componente de barreira esteárica para o controle da agregação. O lipídeo modificado está presente dentro das vesículas previamente formadas numa quantidade eficaz para retardar, porém não impedir, a agregação das vesículas previamente formadas. Numa incorporação preferencial da presente invenção, eficaz no sentido de proporcionar uma formação de partículas de lipídeos eficiente em larga escala (por exemplo 20-200 litros), uma solução de agente terapêutico compreendendo ácidos nucleicos (por exemplo oligodeoxinucleotídeos antisense) é combinada com vesículas de lipídeos previamente formadas numa solução 25-40 % de etanol aquoso. A incubação desta mistura por um período de cerca de 1 hora é suficiente para resultar na produção espontânea de partículas de agente terapêutico completamente encapsuladas.
BRPI0012624-1A 1999-07-15 2000-07-14 métodos para a preparação de agentes terapêuticos envolvidos por lipìdeos. BR0012624B1 (pt)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US14397899P 1999-07-15 1999-07-15
US60/143,978 1999-07-15
PCT/CA2000/000843 WO2001005374A1 (en) 1999-07-15 2000-07-14 Methods for preparation of lipid-encapsulated therapeutic agents

Publications (2)

Publication Number Publication Date
BR0012624A true BR0012624A (pt) 2002-04-02
BR0012624B1 BR0012624B1 (pt) 2011-08-09

Family

ID=22506531

Family Applications (1)

Application Number Title Priority Date Filing Date
BRPI0012624-1A BR0012624B1 (pt) 1999-07-15 2000-07-14 métodos para a preparação de agentes terapêuticos envolvidos por lipìdeos.

Country Status (11)

Country Link
EP (2) EP1194122B1 (pt)
JP (3) JP5388395B2 (pt)
CN (1) CN1228041C (pt)
AT (1) ATE286719T1 (pt)
AU (2) AU771706B2 (pt)
BR (1) BR0012624B1 (pt)
CA (2) CA2378438C (pt)
DE (1) DE60017406T2 (pt)
ES (1) ES2235916T3 (pt)
IL (2) IL147089A0 (pt)
WO (2) WO2001005373A1 (pt)

Families Citing this family (74)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020119188A1 (en) * 2000-02-08 2002-08-29 Susan Niemiec Method of manufacturing liposomes
AU2001254548B2 (en) * 2000-04-20 2006-09-28 The University Of British Columbia Enhanced stabilised plasmid-lipid particle-mediated transfection using endosomal membrane
US7189705B2 (en) 2000-04-20 2007-03-13 The University Of British Columbia Methods of enhancing SPLP-mediated transfection using endosomal membrane destabilizers
WO2003075890A1 (en) * 2002-03-05 2003-09-18 Transave, Inc. Methods for entrapment of bioactive agent in a liposome or lipid complex
CA2486007C (en) 2002-05-15 2011-11-22 California Pacific Medical Center Delivery of nucleic acid-like compounds
ATE444062T1 (de) 2002-06-26 2009-10-15 Medigene Ag Herstellung einer kationisch liposomalen zubereitung, einen lipophilen wirkstoff enthaltend
EP2823809B1 (en) * 2002-06-28 2016-11-02 Protiva Biotherapeutics Inc. Method and apparatus for producing liposomes
US7718189B2 (en) 2002-10-29 2010-05-18 Transave, Inc. Sustained release of antiinfectives
EP2567693B1 (en) * 2003-07-16 2015-10-21 Protiva Biotherapeutics Inc. Lipid encapsulated interfering RNA
CN102940891B (zh) 2004-05-05 2016-02-24 赛伦斯治疗有限公司 脂质、脂质复合物及其应用
WO2005121348A1 (en) * 2004-06-07 2005-12-22 Protiva Biotherapeutics, Inc. Lipid encapsulated interfering rna
EP1781593B1 (en) * 2004-06-07 2011-12-14 Protiva Biotherapeutics Inc. Cationic lipids and methods of use
AU2005259799A1 (en) 2004-07-02 2006-01-12 Protiva Biotherapeutics, Inc. Immunostimulatory siRNA molecules and uses therefor
SG158175A1 (en) * 2004-12-27 2010-01-29 Silence Therapeutics Ag Lipid complexes coated with peg and their use
WO2007012191A1 (en) 2005-07-27 2007-02-01 Protiva Biotherapeutics, Inc. Systems and methods for manufacturing liposomes
JP5336853B2 (ja) 2005-11-02 2013-11-06 プロチバ バイオセラピューティクス インコーポレイティッド 修飾siRNA分子およびその使用法
AU2006322076C1 (en) 2005-12-08 2013-11-14 Insmed Incorporated Lipid-based compositions of antiinfectives for treating pulmonary infections
EP2004141A2 (en) * 2006-03-17 2008-12-24 Novosom AG An efficient method for loading amphoteric liposomes with nucleic acid active substances
EP2012750B1 (en) * 2006-04-06 2018-02-21 Insmed Incorporated Methods for coacervation induced liposomal encapsulation and formulations thereof
CN102321626B (zh) 2006-07-21 2014-12-10 赛伦斯治疗有限公司 用于抑制蛋白激酶3表达的方法
US20100196455A1 (en) 2007-05-04 2010-08-05 Transave, Inc. Compositions of Multicationic Drugs for Reducing Interactions with Polyanionic Biomolecules and Methods of Use Thereof
US9119783B2 (en) 2007-05-07 2015-09-01 Insmed Incorporated Method of treating pulmonary disorders with liposomal amikacin formulations
US9114081B2 (en) 2007-05-07 2015-08-25 Insmed Incorporated Methods of treating pulmonary disorders with liposomal amikacin formulations
US9333214B2 (en) 2007-05-07 2016-05-10 Insmed Incorporated Method for treating pulmonary disorders with liposomal amikacin formulations
WO2009038540A1 (en) * 2007-09-17 2009-03-26 Microspace Rapid Pte Ltd System and method for providing control of a vehicle
PT2279254T (pt) 2008-04-15 2017-09-04 Protiva Biotherapeutics Inc Novas formulações lipídicas para entrega de ácido nucleico
PL2350043T3 (pl) 2008-10-09 2014-09-30 Tekmira Pharmaceuticals Corp Ulepszone aminolipidy i sposoby dostarczania kwasów nukleinowych
AU2009305639B2 (en) 2008-10-16 2016-06-23 Marina Biotech, Inc. Processes and compositions for liposomal and efficient delivery of gene silencing therapeutics
MX2011006562A (es) * 2008-12-17 2011-09-27 Oncothyreon Inc Metodo para elaborar liposomas pequeños.
CA2767129C (en) 2009-07-01 2015-01-06 Protiva Biotherapeutics, Inc. Compositions and methods for silencing apolipoprotein b
US9018187B2 (en) 2009-07-01 2015-04-28 Protiva Biotherapeutics, Inc. Cationic lipids and methods for the delivery of therapeutic agents
CA2767127A1 (en) 2009-07-01 2011-01-06 Protiva Biotherapeutics, Inc. Novel lipid formulations for delivery of therapeutic agents to solid tumors
WO2011005769A1 (en) 2009-07-06 2011-01-13 Variation Biotechnologies, Inc. Methods for preparing vesicles and formulations produced therefrom
US9907746B2 (en) 2009-07-06 2018-03-06 Variation Biotechnologies, Inc. Methods for preparing vesicles and formulations produced therefrom
WO2011056682A1 (en) 2009-10-27 2011-05-12 The University Of British Columbia Reverse head group lipids, lipid particle compositions comprising reverse headgroup lipids, and methods for the delivery of nucleic acids
WO2011120023A1 (en) 2010-03-26 2011-09-29 Marina Biotech, Inc. Nucleic acid compounds for inhibiting survivin gene expression uses thereof
EP2558074B1 (en) 2010-04-08 2018-06-06 The Trustees of Princeton University Preparation of lipid nanoparticles
WO2011133584A2 (en) 2010-04-19 2011-10-27 Marina Biotech, Inc. Nucleic acid compounds for inhibiting hras gene expression and uses thereof
WO2011139842A2 (en) 2010-04-28 2011-11-10 Marina Biotech, Inc. Nucleic acid compounds for inhibiting fgfr3 gene expression and uses thereof
WO2012000104A1 (en) 2010-06-30 2012-01-05 Protiva Biotherapeutics, Inc. Non-liposomal systems for nucleic acid delivery
US9610248B2 (en) 2010-07-06 2017-04-04 Variation Biotechnologies, Inc. Compositions and methods for treating influenza
BR112013017939B1 (pt) * 2011-01-13 2022-11-16 Variation Biotechnologies Inc Composição imunogênica liofilizada termoestável, uso e método para preparação da mesma
US9579338B2 (en) * 2011-11-04 2017-02-28 Nitto Denko Corporation Method of producing lipid nanoparticles for drug delivery
JP6133883B2 (ja) 2011-11-04 2017-05-24 日東電工株式会社 薬物送達用の脂質ナノ粒子の生成方法
AU2013208693B2 (en) 2012-01-12 2017-12-07 Variation Biotechnologies Inc. Compositions and methods for treating viral infections
EP4008354A1 (en) 2012-01-27 2022-06-08 Variation Biotechnologies Inc. Methods and compositions for therapeutic agents
KR102092361B1 (ko) 2012-05-21 2020-03-23 인스메드 인코포레이티드 폐 감염을 치료하기 위한 시스템
MX2015006681A (es) 2012-11-29 2016-04-06 Insmed Inc Formulaciones de vancomicina estabilizadas.
CN105188674B (zh) * 2013-03-14 2017-12-08 生物休眠有限公司 脂质体制剂及制造
US9993427B2 (en) 2013-03-14 2018-06-12 Biorest Ltd. Liposome formulation and manufacture
US9693958B2 (en) 2013-03-15 2017-07-04 Cureport, Inc. Methods and devices for preparation of lipid nanoparticles
US9504405B2 (en) 2013-10-23 2016-11-29 Verily Life Sciences Llc Spatial modulation of magnetic particles in vasculature by external magnetic field
US10542918B2 (en) 2013-10-23 2020-01-28 Verily Life Sciences Llc Modulation of a response signal to distinguish between analyte and background signals
ES2981634T3 (es) 2014-05-15 2024-10-09 Insmed Incorporated Métodos para tratar infecciones micobacterianas pulmonares no tuberculosas
AU2015283954B2 (en) * 2014-07-02 2020-11-12 Translate Bio, Inc. Encapsulation of messenger RNA
US9861710B1 (en) 2015-01-16 2018-01-09 Verily Life Sciences Llc Composite particles, methods, and in vivo diagnostic system
EP3638215A4 (en) 2017-06-15 2021-03-24 Modernatx, Inc. RNA FORMULATIONS
AU2018326799A1 (en) 2017-08-31 2020-02-27 Modernatx, Inc. Methods of making lipid nanoparticles
CN111246845A (zh) 2017-10-20 2020-06-05 生物技术Rna制药有限公司 适用于治疗的脂质体rna制剂的制备和储存
EP3773505A4 (en) 2018-03-30 2021-12-22 Insmed Incorporated PROCESS FOR THE CONTINUOUS MANUFACTURING OF LIPOSOMAL MEDICINAL PRODUCTS
EP3843709A1 (en) 2018-08-29 2021-07-07 Translate Bio, Inc. Improved process of preparing mrna-loaded lipid nanoparticles
EP3620519A1 (en) * 2018-09-04 2020-03-11 F. Hoffmann-La Roche AG Use of isolated milk extracellular vesicles for delivering oligonucleotides orally
CN113271926A (zh) 2018-09-20 2021-08-17 摩登纳特斯有限公司 脂质纳米颗粒的制备及其施用方法
RU2697390C1 (ru) * 2019-03-15 2019-08-14 Федеральное государственное бюджетное образовательное учреждение высшего образования "Кемеровский государственный медицинский университет" Министерства здравоохранения Российской Федерации Способ синтеза липосомальной формы тироксина
CA3133858A1 (en) 2019-03-19 2020-09-24 Arcturus Therapeutics, Inc. Method of making lipid-encapsulated rna nanoparticles
EP3711749A1 (en) 2019-03-19 2020-09-23 Polymun Scientific Immunbiologische Forschung GmbH Method of making lipid nanoparticles
BR112021022182A2 (pt) 2019-05-07 2021-12-21 Univ Do Minho Método para produção de lipossomas.
EP4110296A1 (en) 2020-02-25 2023-01-04 Translate Bio, Inc. Improved processes of preparing mrna-loaded lipid nanoparticles
KR20230065281A (ko) 2020-09-13 2023-05-11 아크투루스 쎄라퓨틱스, 인크. 큰 rna의 지질 나노입자 캡슐화
CA3200234A1 (en) 2020-11-25 2022-06-02 Daryl C. Drummond Lipid nanoparticles for delivery of nucleic acids, and related methods of use
EP4059491A1 (de) 2021-03-17 2022-09-21 Evonik Operations GmbH Vorrichtung und verfahren zur herstellung von nanocarriern und/oder nanoformulierungen
US12064479B2 (en) 2022-05-25 2024-08-20 Akagera Medicines, Inc. Lipid nanoparticles for delivery of nucleic acids and methods of use thereof
WO2024175455A1 (en) 2023-02-23 2024-08-29 Evonik Operations Gmbh Easy-to-handle liposome extruder
WO2024175457A1 (en) 2023-02-23 2024-08-29 Evonik Operations Gmbh Small scale liposome extruder

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4752425A (en) * 1986-09-18 1988-06-21 Liposome Technology, Inc. High-encapsulation liposome processing method
US4895452A (en) * 1988-03-03 1990-01-23 Micro-Pak, Inc. Method and apparatus for producing lipid vesicles
JPH0665382B2 (ja) * 1991-03-20 1994-08-24 雪印乳業株式会社 リポソーム調製装置とその装置を使用するリポソーム調製方法
US5776486A (en) * 1993-05-28 1998-07-07 Aphios Corporation Methods and apparatus for making liposomes containing hydrophobic drugs
DE69407292T2 (de) * 1993-06-30 1998-06-25 Genentech Inc Verfahren zur herstellung von liposomen
EP1179340A3 (en) * 1994-09-30 2003-05-07 INEX Pharmaceutical Corp. Compositions for the introduction of polyanionic materials into cells
JP4656675B2 (ja) * 1997-05-14 2011-03-23 ユニバーシティー オブ ブリティッシュ コロンビア 脂質小胞への荷電した治療剤の高率封入
ATE355826T1 (de) * 1997-10-10 2007-03-15 Inex Pharmaceuticals Corp Verfahren zur verkapselung von nukleinsäuren in lipiddoppelschichten
EP1030652B1 (en) * 1997-11-14 2012-04-25 Pacira Pharmaceuticals, Inc. Production of multivesicular liposomes
JP2002529240A (ja) * 1998-11-13 2002-09-10 オプタイム セラピュウティクス, インコーポレイテッド リポソーム生成のための方法および装置

Also Published As

Publication number Publication date
ATE286719T1 (de) 2005-01-15
ES2235916T3 (es) 2005-07-16
CA2378438A1 (en) 2001-01-25
EP1194122A1 (en) 2002-04-10
JP5388395B2 (ja) 2014-01-15
AU769357B2 (en) 2004-01-22
DE60017406D1 (de) 2005-02-17
AU6256200A (en) 2001-02-05
JP2003504391A (ja) 2003-02-04
DE60017406T2 (de) 2005-09-29
BR0012624B1 (pt) 2011-08-09
IL147089A (en) 2006-08-20
IL147089A0 (en) 2002-08-14
WO2001005374A1 (en) 2001-01-25
EP1196145A1 (en) 2002-04-17
CN1361681A (zh) 2002-07-31
JP2003504390A (ja) 2003-02-04
WO2001005373A9 (en) 2002-08-29
JP2011225618A (ja) 2011-11-10
AU771706B2 (en) 2004-04-01
CA2378430A1 (en) 2001-01-25
EP1194122B1 (en) 2005-01-12
WO2001005373A1 (en) 2001-01-25
AU6256100A (en) 2001-02-05
CN1228041C (zh) 2005-11-23
CA2378438C (en) 2010-05-04

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B25A Requested transfer of rights approved

Owner name: THE UNIVERSITY OF BRITISH COLUMBIA (CA)

Free format text: TRANSFERIDO DE: INEX PHARMACEUTICALS CORP.

B07A Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]
B06F Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]

Free format text: DE ACORDO COM ART. 34 " II " DA LPI ( LEI 9279, DE 14/05/96 ) , O EXAME FICA SUSPENSO PARA QUE O REQUERENTE APRESENTE DOCUMENTOS NECESSARIOS A REGULARIZACAO DO PROCESSO E EXAME DO PEDIDO.

B09A Decision: intention to grant [chapter 9.1 patent gazette]
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Free format text: PRAZO DE VALIDADE: 10 (DEZ) ANOS CONTADOS A PARTIR DE 09/08/2011, OBSERVADAS AS CONDICOES LEGAIS.

B21F Lapse acc. art. 78, item iv - on non-payment of the annual fees in time

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B24J Lapse because of non-payment of annual fees (definitively: art 78 iv lpi, resolution 113/2013 art. 12)

Free format text: EM VIRTUDE DA EXTINCAO PUBLICADA NA RPI 2259 DE 22-04-2014 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDA A EXTINCAO DA PATENTE E SEUS CERTIFICADOS, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013.