DK3046584T3 - Terapeutiske polymere nanopartikler og fremgangsmåder til fremstilling og anvendelse deraf - Google Patents
Terapeutiske polymere nanopartikler og fremgangsmåder til fremstilling og anvendelse deraf Download PDFInfo
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- DK3046584T3 DK3046584T3 DK14772420.7T DK14772420T DK3046584T3 DK 3046584 T3 DK3046584 T3 DK 3046584T3 DK 14772420 T DK14772420 T DK 14772420T DK 3046584 T3 DK3046584 T3 DK 3046584T3
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Claims (24)
1. Terapeutisk nanopartikel, der omfatter 55 til 85 vægtprocent diblok-polymælkesyre-polyethylenglycol- copolymer, hvor den terapeutiske nanopartikel omfatter 10 til 30 vægtprocent polyethylenglycol, 5 til 20 vægtprocent pamoinsyre og 10 til 25 vægtprocent 2—(3—((7—(3—(ethyl (2 — hydroxyethyl) amino)propoxy)quinazolin-4-yl)amino)-lH-pyrazol- 5-yl)-N-(3 — fluorphenyl)acetamid ("AZD1152 hqpa")·
2. Terapeutisk nanopartikel ifølge krav 1, hvor polymælkesyre- polyethylenglycol-copolymeren har en talgennemsnitlig molekylvægt på 15 kDa til 20 kDa af polymælkesyre og en talgennemsnitlig molekylvægt på 4 kDa til 6 kDa af polyethylenglycol.
3. Terapeutisk nanopartikel ifølge krav 2, hvor polymælkesyre-polyethylenglycol-copolymeren har en talgennemsnitlig molekylvægt på 16 kDa af polymælkesyre og en talgennemsnitlig molekylvægt på 5 kDa af polyethylenglycol.
4. Terapeutisk nanopartikel ifølge et hvilket som helst af kravene 1 til 3, der omfatter 15 til 22 vægtprocent AZD1152 hqpa.
5. Terapeutisk nanopartikel ifølge krav 1, der omfatter 15 til 25 vægtprocent AZD1152 hqpa, 7 til 15 vægtprocent pamoinsyre og en diblok-polymælkesyre-polyethylenglycol- copolymer, hvor den terapeutiske nanopartikel omfatter 10 til 30 vægtprocent polyethylenglycol, og polymælkesyre- polyethylenglycol-copolymeren har en talgennemsnitlig molekylvægt på 16 kDa af polymælkesyre og en talgennemsnitlig molekylvægt på 5 kDa af polyethylenglycol.
6. Terapeutisk nanopartikel ifølge krav 1, der omfatter 15 til 22 vægtprocent AZD1152 hqpa, 7 til 10 vægtprocent pamoinsyre og en diblok-polymælkesyre-polyethylenglycol- copolymer, hvor den terapeutiske nanopartikel omfatter 10 til 30 vægtprocent polyethylenglycol, og polymælkesyre- polyethylenglycol-copolymeren har en talgennemsnitlig molekylvægt på 16 kDa af polymælkesyre og en talgennemsnitlig molekylvægt på 5 kDa af polyethylenglycol; hvor mindre end 20 % AZD1152 hgpa er frigivet fra nanopartiklen efter 30 timer i PBS og polysorbat20 ved 37 °C.
7. Terapeutisk nanopartikel ifølge krav 1, der omfatter 15 til 22 vægtprocent AZD1152 hqpa, 7 til 10 vægtprocent pamoinsyre og en diblok-polymælkesyre-polyethylenglycol- copolymer, hvor den terapeutiske nanopartikel omfatter 10 til 30 vægtprocent polyethylenglycol, og polymælkesyre- polyethylenglycol-copolymeren har en talgennemsnitlig molekylvægt på 16 kDa af polymælkesyre og en talgennemsnitlig molekylvægt på 5 kDa af polyethylenglycol; hvor mindre end 20 % AZD1152 hqpa er frigivet fra nanopartiklen efter 30 timer i PBS og polysorbat20 ved 37 °C, og hvor nanopartiklerne er fremstillet ved hjælp af en fremgangsmåde, der omfatter følgende trin: 1) kombinering af en første organisk fase, der omfatter en 16:5 PLA-PEG-copolymer, AZD1152 hqpa og pamoinsyre i en opløsningsblanding, der omfatter TFA, benzylalkohol, DMSO og ethylacetat, således at benzylalkohol:ethylacetat er til stede i et molforhold på 1:3,6, og pamoinsyren og AZD1152 hqpa tilsættes ved et indledende molforhold mellem pamoinsyre og AZD1152 hqpa på 0,8:1; med en første vandig opløsning, der omfatter en polyoxyethylen (100)-stearylether i vand, DMSO og benzylalkohol, til frembringelse af en anden fase, hvor forholdet mellem den vandige fase og den organiske fase er 5,5:1; 2) emulgering af den anden fase til frembringelse af en grov emulsion; 3) opbevaring af den grove emulsion i et tidsrum, såsom 10 til 15 minutter, passende ved ca. 0 °C, for eksempel ved nedsænkning i et isbad; 4) frembringelse af en nanoemulsion ved anvendelse af en høj trykshomogenisator; 5) eventuelt afventning i et tidsrum på mindst 5 minutter, for eksempel 10 minutter; 6) bratkøling af emulsionsfasen ved 0-5 °C til derved frembringelse af en bratkølet fase, hvor bratkøling af emulsionsfasen omfatter blanding af emulsionsfasen med en anden vandig opløsning, der omfatter en buffer ved pH 6,5, hvor forholdet mellem den anden vandige opløsning og emulsionen er mellem 2:1 og 10:1, såsom 3:1; 7) tilsætning af en vandig opløsning af overfladeaktivt stof til den bratkølede opløsning; 8) opkoncentrering og isolering af de resulterende nanopartikler ved hjælp af filtrering.
8. Terapeutisk nanopartikel ifølge krav 1, der består af 15- 19 vægt-% AZD1152 hqpa, pamoinsyre i et molforhold på 0,76 i forhold til AZD1152 hqpa og en diblok-polymælkesyre- polyethylenglycol-copolymer, hvor polymælkesyre- polyethylenglycol-copolymeren har en talgennemsnitlig molekylvægt på 16 kDa af polymælkesyre og en talgennemsnitlig molekylvægt på 5 kDa af polyethylenglycol.
9. Terapeutisk nanopartikel ifølge krav 3, hvor den terapeutiske nanopartikel frigiver mindre end 20 % AZD1152 hqpa efter 30 timer i phosphatbufferopløsning og polysorbat20 ved 37 °C.
10. Terapeutisk nanopartikel ifølge et hvilket som helst af kravene 1 til 9, der har en hydrodynamisk diameter på 70-140 nm.
11. Farmaceutisk acceptabel sammensætning, der omfatter et antal terapeutiske nanopartikler ifølge et hvilket som helst af kravene 1 til 10 og et eller flere farmaceutisk acceptable excipienser, fortyndingsmidler og/eller bærestoffer.
12. Terapeutisk nanopartikel ifølge et hvilket som helst af kravene 1 til 10 til anvendelse som et medikament.
13. Sammensætning ifølge krav 11 til anvendelse som et medikament.
14. Terapeutisk nanopartikel ifølge et hvilket som helst af kravene 1 til 10 til anvendelse som et medikament til behandling af cancer.
15. Sammensætning ifølge krav 11 til anvendelse som et medikament til behandling af cancer.
16. Terapeutisk nanopartikel til anvendelse som et medikament til behandling af cancer ifølge krav 14, hvor canceren er lungecancer, kolorektal cancer eller en hæmatologisk cancer, såsom akut myeloid leukæmi (AML) eller diffus storcellet B-cellelymfom (DLBCL) .
17. Sammensætning til anvendelse som et medikament til behandling af cancer ifølge krav 15, hvor canceren er lungecancer, kolorektal cancer eller en hæmatologisk cancer, såsom AML eller DLBCL.
18. Kombination, der er egnet til anvendelse til behandling af cancer, der omfatter en farmaceutisk acceptabel sammensætning ifølge krav 11 og et andet antitumormiddel.
19. Kombination ifølge krav 18, hvor det andet antitumormiddel er valgt blandt: a) standardkemoterapiregimer, der indbefatter erstattende eller supplerende mitosehæmmende kemoterapier ved faste tumorer og hæmatologiske cancere, såsom taxaner og vinca-alkaloider; b) terapier, der er målrettet DNA-skaderesponset, herunder midler, der hæmmer reparation af DNA-skade og cellecyklen; og c) immunmedierede terapier, herunder hæmmere af blokering af immun checkpoint, såsom CTLA4-, PD-1- og PDL-l-målrettede terapier.
20. Kit af dele, der omfatter: a) en lyofiliseret farmaceutisk sammensætning, der omfatter nanopartikler ifølge et hvilket som helst af kravene 1 til 10; og b) en brugsanvisning.
21. Fremgangsmåde til fremstilling af en terapeutisk nanopartikel ifølge krav 1, hvilken fremgangsmåde omfatter: 1) kombinering af en første organisk fase, der omfatter en polymer i ethylacetat, AZD1152 hgpa i et TFA/vand/benzylalkohol-opløsningssystem og pamoinsyre i DMSO, med en første vandig opløsning, der omfatter et overfladeaktivt stof, såsom natriumcholat eller polyoxyethylen (100)-stearylether, i vand og benzylalkohol til frembringelse af en anden fase; 2) emulgering af den anden fase til frembringelse af en emulsion; 3) bratkøling af emulsionsfasen ved < 5 °C til derved frembringelse af en bratkølet fase, hvor bratkøling af emulsionsfasen omfatter blanding af emulsionsfasen med en anden vandig opløsning med et pH på mellem 4 og 7; 4) tilsætning af en vandig opløsning af overfladeaktivt stof; 5) opkoncentrering og isolering af de resulterende nanopartikler ved hjælp af filtrering.
22. Fremgangsmåde ifølge krav 21, der omfatter 1) kombinering af en første organisk fase, der omfatter en polymer i ethylacetat, AZD1152 hqpa i et TFA/vand/benzylalkohol-opløsningssystem og pamoinsyre i DMSO, med en første vandig opløsning, der omfatter et overfladeaktivt stof, såsom natriumcholat eller polyoxyethylen (100)-stearylether, i vand, DMSO og benzylalkohol til frembringelse af en anden fase; 2) emulgering af den anden fase til frembringelse af en grov emulsion; 3) opbevaring af den grove emulsion i et tidsrum; 4) frembringelse af en nanoemulsion ved anvendelse af en høj trykshomogenisator; 5) eventuelt afventning i et tidsrum på mindst 5 minutter; 6) bratkøling af emulsionsfasen ved 0-5 °C til derved frembringelse af en bratkølet fase, hvor bratkøling af emulsionsfasen omfatter blanding af emulsionsfasen med en anden vandig opløsning, der omfatter en buffer med et pH på mellem 4 og 7, såsom pH 6,5; 7) tilsætning af en vandig opløsning af overfladeaktivt stof; 8) opkoncentrering og isolering af de resulterende nanopartikler ved hjælp af filtrering.
23. Fremgangsmåde ifølge krav 22, der omfatter: 1) kombinering af en første organisk fase, der omfatter en 16/5 PLA-PEG copolymer, AZD1152 hqpa og pamoinsyre i en opløsningsblanding, der omfatter TFA, benzylalkohol, DMSO og ethylacetat, således at benzylalkohol:ethylacetat er til stede i et molforhold på 1:3,6, med en første vandig opløsning, der omfatter et overfladeaktivt stof, såsom polyoxyethylen (100)-stearylether, i vand, DMSO og benzylalkohol til frembringelse af en anden fase; 2) emulgering af den anden fase til frembringelse af en grov emulsion; 3) opbevaring af den grove emulsion i et tidsrum; 4) frembringelse af en nanoemulsion ved anvendelse af en høj trykshomogenisator; 5) eventuelt afventning i et tidsrum på mindst 5 minutter; 6) bratkøling af emulsionsfasen ved 0-5 °C til derved frembringelse af en bratkølet fase, hvor bratkøling af emulsionsfasen omfatter blanding af emulsionsfasen med en anden vandig opløsning, der omfatter buffer, ved pH 6,5; 7) tilsætning af en vandig opløsning af overfladeaktivt stof som et opløsningsmiddel; 8) opkoncentrering og isolering af de resulterende nanopartikler ved hjælp af filtrering.
24. Fremgangsmåde ifølge krav 23, hvor pamoinsyren og AZD1152 hqpa tilsættes ved et indledende molforhold mellem pamoinsyre og AZD1152 hqpa på 0,8:1.
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Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK3104838T3 (da) | 2014-02-13 | 2020-02-24 | Pfizer | Terapeutiske nanopartikler omfattende et terapeutisk middel og fremgangsmåder til fremstilling og anvendelse deraf |
US9428470B2 (en) | 2014-02-13 | 2016-08-30 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
WO2017081606A1 (en) * | 2015-11-10 | 2017-05-18 | Pfizer Inc. | Methods of determining features of polymeric nanoparticles that include a therapeutic agent |
CA3005957A1 (en) * | 2015-11-25 | 2017-06-01 | Pfizer Inc. | Therapeutic nanoparticles comprising an antibiotic and methods of making and using same |
JP6579948B2 (ja) * | 2015-12-24 | 2019-09-25 | 株式会社日立ハイテクノロジーズ | 生体ポリマを分析するための測定試薬及び分析デバイス |
WO2017163145A1 (en) * | 2016-03-22 | 2017-09-28 | Pfizer Inc. | Process for preparing therapeutic nanoparticles |
JP7082110B2 (ja) * | 2017-03-29 | 2022-06-07 | テルモ株式会社 | アジュバント組成物およびこれを含むワクチン組成物並びに薬剤キット |
TW202019440A (zh) | 2018-07-30 | 2020-06-01 | 瑞典商阿斯特捷利康公司 | 用於治療癌症之組合療法 |
TW202023568A (zh) * | 2018-07-30 | 2020-07-01 | 瑞典商阿斯特捷利康公司 | 用於治療癌症之組合療法 |
JP2022532462A (ja) * | 2019-02-02 | 2022-07-15 | ナノブリッド イノベーションズ プライベート リミテッド | 脂質-ポリマーハイブリッドナノ粒子 |
EP4003596A4 (en) | 2019-07-31 | 2023-08-16 | Cytovale Inc. | SYSTEM AND METHOD FOR DETERMINING IMMUNE ACTIVITY |
WO2021037933A1 (en) | 2019-08-28 | 2021-03-04 | Astrazeneca Ab | Combination of azd2811 nanoparticles, 5-azacitidine and venetoclax for use in the treatment of cancer |
WO2021094379A1 (en) | 2019-11-12 | 2021-05-20 | Astrazeneca Ab | Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of cancer |
WO2021224381A1 (en) | 2020-05-07 | 2021-11-11 | Astrazeneca Ab | Combination therapy for treating cancer |
WO2021260582A1 (en) | 2020-06-24 | 2021-12-30 | Astrazeneca Uk Limited | Combination of antibody-drug conjugate and aurora b inhibitor |
WO2022192139A1 (en) | 2021-03-10 | 2022-09-15 | Astrazeneca Ab | Aurora kinase b inhibitors for use for treating cancer |
US11548003B1 (en) * | 2022-01-13 | 2023-01-10 | CytoVale Inc. | System and method for determining an immune activation state |
US11592371B1 (en) | 2022-01-13 | 2023-02-28 | CytoVale Inc. | System and method for determining an immune activation state |
US11964281B2 (en) | 2022-02-03 | 2024-04-23 | CytoVale Inc. | System and method for correcting patient index |
WO2023150246A1 (en) * | 2022-02-04 | 2023-08-10 | Virginia Commonwealth University | Sustained release formulations and methods of use thereof |
Family Cites Families (104)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL89029A (en) | 1988-01-29 | 1993-01-31 | Lilly Co Eli | Fungicidal quinoline and cinnoline derivatives, compositions containing them, and fungicidal methods of using them |
GB9017479D0 (en) | 1990-08-09 | 1990-09-26 | Ici Plc | Process |
GB9102727D0 (en) | 1991-02-08 | 1991-03-27 | Ici Plc | Pharmaceutical agent |
AU658646B2 (en) | 1991-05-10 | 1995-04-27 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
US5480883A (en) | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
US5721237A (en) | 1991-05-10 | 1998-02-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties |
US5565215A (en) | 1993-07-23 | 1996-10-15 | Massachusettes Institute Of Technology | Biodegradable injectable particles for imaging |
US5543158A (en) | 1993-07-23 | 1996-08-06 | Massachusetts Institute Of Technology | Biodegradable injectable nanoparticles |
US6007845A (en) | 1994-07-22 | 1999-12-28 | Massachusetts Institute Of Technology | Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers |
GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
TW321649B (da) | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
ATE252894T1 (de) | 1995-01-05 | 2003-11-15 | Univ Michigan | Oberflächen-modifizierte nanopartikel und verfahren für ihre herstellung und verwendung |
EP0752245B1 (en) | 1995-07-05 | 2002-05-22 | European Community | Biocompatible and biodegradable nanoparticles designed for proteinaceous drugs absorption and delivery |
GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
ZA986732B (en) | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitiors of tyrosine kinases |
DK1119567T3 (da) | 1998-10-08 | 2005-07-25 | Astrazeneca Ab | Quinazolinderivater |
FI982733A (fi) | 1998-12-17 | 2000-06-18 | Orion Yhtymae Oyj | Trifenyylietyleeniantiestrogeenien liukoisia koostumuksia |
RU2002110461A (ru) | 1999-09-21 | 2004-03-10 | Астразенека Аб (Se) | Производные хиназолина и их применение в качестве фармацевтических веществ |
GB9922171D0 (en) | 1999-09-21 | 1999-11-17 | Zeneca Ltd | Chemical compounds |
US6316029B1 (en) | 2000-05-18 | 2001-11-13 | Flak Pharma International, Ltd. | Rapidly disintegrating solid oral dosage form |
PL360439A1 (en) | 2000-06-28 | 2004-09-06 | Astrazeneca Ab | Substituted quinazoline derivatives and their use as inhibitors |
US6610677B2 (en) | 2000-09-15 | 2003-08-26 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
EP1372385A1 (en) | 2001-03-30 | 2004-01-02 | Rhodia Inc. | Aqeuous suspension of nanoparticles comprising an agrochemical active ingredient |
AU2002350105A1 (en) | 2001-06-21 | 2003-01-08 | Ariad Pharmaceuticals, Inc. | Novel quinazolines and uses thereof |
GB0124299D0 (en) | 2001-10-10 | 2001-11-28 | Astrazeneca Ab | Crystal structure of enzyme and uses thereof |
ATE371442T1 (de) | 2001-10-12 | 2007-09-15 | Elan Pharma Int Ltd | Zusammensetzungen mit einer kombination aus eigenschaften sofortiger freisetzung und kontrollierter freisetzung |
IL162541A0 (en) | 2001-12-24 | 2005-11-20 | Astrazeneca Ab | Substituted quinazoline derivatives as inhibitors of aurora kinases |
US7638137B2 (en) | 2002-06-05 | 2009-12-29 | University Of Florida Research Foundation, Incorporated | Ophthalmic drug delivery system |
AU2003261167A1 (en) | 2002-07-16 | 2004-02-02 | Elan Pharma International, Ltd | Liquid dosage compositions of stable nanoparticulate active agents |
EP2030611A1 (en) | 2002-07-31 | 2009-03-04 | Alza Corporation | Injectable multimodal polymer depot compositions and uses thereof |
ES2290529T3 (es) * | 2002-12-24 | 2008-02-16 | Astrazeneca Ab | Derivados de fosfonooxiquinazolina y su uso farmaceutico. |
CN102697737B (zh) | 2003-04-03 | 2014-03-19 | 杰西.L.-S.奥 | 负载肿瘤靶向药物的颗粒 |
US7727969B2 (en) | 2003-06-06 | 2010-06-01 | Massachusetts Institute Of Technology | Controlled release nanoparticle having bound oligonucleotide for targeted delivery |
EP2444069B1 (en) * | 2003-07-23 | 2019-06-05 | Evonik Corporation | Controlled release compositions |
US9028829B2 (en) | 2004-02-20 | 2015-05-12 | The Children's Hospital Of Philadelphia | Uniform field magnetization and targeting of therapeutic formulations |
ES2246694B1 (es) | 2004-04-29 | 2007-05-01 | Instituto Cientifico Y Tecnologico De Navarra, S.A. | Nanoparticulas pegiladas. |
WO2007001356A2 (en) | 2004-09-10 | 2007-01-04 | University Of Wyoming | Nanoparticles for cytoplasmic drug delivery to cancer cells |
AU2006235487B2 (en) | 2005-04-12 | 2011-12-22 | Elan Pharma International Limited | Nanoparticulate quinazoline derivative formulations |
US20090022806A1 (en) | 2006-12-22 | 2009-01-22 | Mousa Shaker A | Nanoparticle and polymer formulations for thyroid hormone analogs, antagonists and formulations and uses thereof |
CA2626016A1 (en) | 2005-10-21 | 2007-06-21 | Panacea Biotec Limited | Pharmaceutical composition comprising at least one anticancer drug and at least one polymer |
US9267937B2 (en) | 2005-12-15 | 2016-02-23 | Massachusetts Institute Of Technology | System for screening particles |
WO2010009146A1 (en) | 2008-07-15 | 2010-01-21 | University Of Kansas | Nanoclusters for delivery of poorly water soluble drug nanoparticles |
WO2007074604A1 (ja) | 2005-12-26 | 2007-07-05 | Ltt Bio-Pharma Co., Ltd. | 水溶性非ペプチド性低分子薬物含有ナノ粒子 |
EP2007435B1 (en) | 2006-03-31 | 2019-12-18 | Massachusetts Institute Of Technology | System for targeted delivery of therapeutic agents |
CA2652280C (en) | 2006-05-15 | 2014-01-28 | Massachusetts Institute Of Technology | Polymers for functional particles |
GB0609617D0 (en) | 2006-05-16 | 2006-06-21 | Astrazeneca Ab | Process & intermediate |
GB0609621D0 (en) * | 2006-05-16 | 2006-06-21 | Astrazeneca Ab | Novel co-crystal |
WO2007137117A2 (en) | 2006-05-17 | 2007-11-29 | Massachusetts Institute Of Technology | Aptamer-directed drug delivery |
WO2007150030A2 (en) | 2006-06-23 | 2007-12-27 | Massachusetts Institute Of Technology | Microfluidic synthesis of organic nanoparticles |
CA2659687A1 (en) | 2006-07-31 | 2008-02-07 | Senju Pharmaceutical Co., Ltd. | Aqueous liquid preparation containing amide compound |
US20100144845A1 (en) | 2006-08-04 | 2010-06-10 | Massachusetts Institute Of Technology | Oligonucleotide systems for targeted intracellular delivery |
US20100303723A1 (en) | 2006-11-20 | 2010-12-02 | Massachusetts Institute Of Technology | Drug delivery systems using fc fragments |
US20100015050A1 (en) | 2006-12-21 | 2010-01-21 | Wayne State University | Peg and targeting ligands on nanoparticle surface |
PL2481402T3 (pl) | 2007-03-07 | 2018-11-30 | Abraxis Bioscience, Llc | Nanocząstka zawierająca rapamycynę i albuminę jako środek przeciwnowotworowy |
US20090074828A1 (en) | 2007-04-04 | 2009-03-19 | Massachusetts Institute Of Technology | Poly(amino acid) targeting moieties |
JP2010524859A (ja) | 2007-04-13 | 2010-07-22 | ユニバーシティー オブ ノース テキサス ヘルス サイエンス センター アット フォートワース | 標的型癌ナノ治療に用いる、活性剤が負荷された活性化plgaナノ粒子製剤 |
CN101678113B (zh) | 2007-05-14 | 2012-05-30 | 日本株式会社Ltt生物医药 | 缓释性的含有带负电荷基团的低分子药物的纳米粒子 |
SI2200588T1 (sl) | 2007-09-25 | 2019-08-30 | Solubest Ltd. | Sestavki, ki obsegajo lipofilne aktivne spojine, in postopek za njihovo pripravo |
US8974814B2 (en) | 2007-11-12 | 2015-03-10 | California Institute Of Technology | Layered drug delivery polymer monofilament fibers |
US9422234B2 (en) | 2007-11-30 | 2016-08-23 | The Johns Hopkins University | Prostate specific membrane antigen (PSMA) targeted nanoparticles for therapy of prostate cancer |
WO2009073193A2 (en) | 2007-12-03 | 2009-06-11 | The Johns Hopkins University | Methods of synthesis and use of chemospheres |
KR100961880B1 (ko) | 2007-12-12 | 2010-06-09 | 중앙대학교 산학협력단 | 밀링에 의한 기능성 약물나노입자의 제조방법 및 상기제조방법에 의해 입자 표면이 개질된 약물나노입자 제제 |
WO2009117410A2 (en) | 2008-03-17 | 2009-09-24 | Board Of Regents, The University Of Texas System | Formation of nanostructured particles of poorly water soluble drugs and recovery by mechanical techniques |
WO2009126401A1 (en) * | 2008-04-10 | 2009-10-15 | Abraxis Bioscience, Llc | Compositions of hydrophobic taxane derivatives and uses thereof |
WO2010005721A2 (en) | 2008-06-16 | 2010-01-14 | Bind Biosciences, Inc. | Drug loaded polymeric nanoparticles and methods of making and using same |
US20090312402A1 (en) | 2008-05-20 | 2009-12-17 | Contag Christopher H | Encapsulated nanoparticles for drug delivery |
ES2721850T3 (es) | 2008-06-16 | 2019-08-05 | Pfizer | Nanopartículas poliméricas terapéuticas que comprenden alcaloides vinca y procedimientos de fabricación y uso de las mismas |
US20100104645A1 (en) | 2008-06-16 | 2010-04-29 | Bind Biosciences, Inc. | Methods for the preparation of targeting agent functionalized diblock copolymers for use in fabrication of therapeutic targeted nanoparticles |
US8613951B2 (en) | 2008-06-16 | 2013-12-24 | Bind Therapeutics, Inc. | Therapeutic polymeric nanoparticles with mTor inhibitors and methods of making and using same |
CN102099016A (zh) * | 2008-06-16 | 2011-06-15 | 佰恩德生物科学股份有限公司 | 载药的聚合物纳米微粒及其制备和使用方法 |
US20100087337A1 (en) | 2008-09-10 | 2010-04-08 | Bind Biosciences, Inc. | High Throughput Fabrication of Nanoparticles |
WO2010042555A2 (en) | 2008-10-06 | 2010-04-15 | The Brigham And Women's Hospital, Inc. | Particles with multiple functionalized surface domains |
US20110125090A1 (en) | 2008-11-13 | 2011-05-26 | Peyman Gholam A | Ophthalmic drug delivery system and method |
WO2010068866A2 (en) | 2008-12-12 | 2010-06-17 | Bind Biosciences | Therapeutic particles suitable for parenteral administration and methods of making and using same |
ES2776126T3 (es) | 2008-12-15 | 2020-07-29 | Pfizer | Nanopartículas de circulación prolongada para la liberación sostenida de agentes terapéuticos |
US20100196907A1 (en) * | 2009-01-31 | 2010-08-05 | Abbott Laboratories | Markers to predict and monitor response to aurora kinase b inhibitor therapy |
US20120052041A1 (en) | 2009-02-04 | 2012-03-01 | The Brigham And Women's Hospital, Inc. | Polymeric nanoparticles with enhanced drug-loading and methods of use thereof |
EP2482818A4 (en) * | 2009-09-29 | 2014-04-09 | Eyegate Pharmaceuticals Inc | POSITIVELY CHARGED POLY (D, L-LACTIDE-CO-GLYCOLIDE) NANOPARTICLES AND METHODS OF MAKING SAME |
US7772274B1 (en) | 2009-10-19 | 2010-08-10 | Scidose, Llc | Docetaxel formulations with lipoic acid |
MX343747B (es) | 2009-11-24 | 2016-11-22 | Medimmune Ltd | Agentes de union diana contra b7-h1. |
EA201290497A1 (ru) | 2009-12-15 | 2013-01-30 | Байнд Байосайенсиз, Инк. | Терапевтические полимерные наночастицы, включающие кортикостероиды, и способы получения таковых |
ES2780156T3 (es) | 2009-12-15 | 2020-08-24 | Pfizer | Composiciones terapéuticas de nanopartículas poliméricas con alta temperatura de transición vítrea o copolímeros de alto peso molecular |
WO2011084521A2 (en) | 2009-12-15 | 2011-07-14 | Bind Biosciences, Inc. | Therapeutic polymeric nanoparticles comprising epothilone and methods of making and using same |
ES2384060B1 (es) | 2010-03-24 | 2013-09-23 | Lipotec S.A. | Cápsulas de nanopartículas lipídicas. |
WO2011119262A1 (en) | 2010-03-26 | 2011-09-29 | Cerulean Pharma Inc. | Methods and systems for generating nanoparticles |
ES2661978T3 (es) | 2010-05-26 | 2018-04-04 | Selecta Biosciences, Inc. | Vacunas multivalentes de nanovehículos sintéticos |
WO2012074588A2 (en) | 2010-08-30 | 2012-06-07 | President And Fellows Of Harvard College | Shear controlled release for stenotic lesions and thrombolytic therapies |
WO2012039979A2 (en) | 2010-09-10 | 2012-03-29 | The Johns Hopkins University | Rapid diffusion of large polymeric nanoparticles in the mammalian brain |
ES2386177B1 (es) | 2010-09-21 | 2013-09-23 | Lipotec, S.A. | Nanocapsulas conteniendo microemulsiones |
WO2012040513A1 (en) | 2010-09-22 | 2012-03-29 | The Board Of Regents Of The University Of Texas System | Compositions and methods for the delivery of beta lapachone |
US20150093440A1 (en) | 2010-10-15 | 2015-04-02 | Glaxo Group Limited | Aggregate nanoparticulate medicament formulations, manufacture and use thereof |
EP2629760A4 (en) | 2010-10-22 | 2014-04-02 | Bind Therapeutics Inc | THERAPEUTIC NANOPARTICLES CONTAINING COPOLYMERS OF HIGH MOLECULAR WEIGHT |
KR101304597B1 (ko) | 2010-11-02 | 2013-09-12 | 한남대학교 산학협력단 | 멀티-코어 구조를 갖는 생체적합성 입자의 제조방법 및 이에 의해 제조된 멀티-코어 구조를 갖는 생체적합성 입자 |
FR2967581B1 (fr) | 2010-11-19 | 2012-12-28 | Sanofi Aventis | Conjugues polymeriques de principes actifs, leur procede de preparation et leurs intermediaires polymeriques |
US20140079642A1 (en) | 2011-01-24 | 2014-03-20 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd | Nanoparticles based for dermal and systemic delivery of drugs |
US20140035438A1 (en) | 2011-04-12 | 2014-02-06 | Massachusetts Institute Of Technology | Passive, Self-Tuning Energy Harvester for Extracting Energy From Rotational Motion |
US20150017245A1 (en) | 2011-09-22 | 2015-01-15 | Bind Therapeutics, Inc. | Methods of treating cancers with therapeutic nanoparticles |
WO2013090840A1 (en) | 2011-12-15 | 2013-06-20 | Gilead Sciences, Inc. | 2 -amino- pyrido [3, 2 -d] pyrimidine derivatives as hcv inhibitors |
CA2865700C (en) | 2012-02-29 | 2020-05-05 | Merck Patent Gmbh | Process for the production of nanoparticles laden with active compound |
CN104394891B (zh) | 2012-03-16 | 2019-04-16 | 约翰霍普金斯大学 | 用于递送活性剂的非线性多嵌段共聚物-药物结合物 |
JP2015529683A (ja) * | 2012-09-17 | 2015-10-08 | バインド セラピューティックス インコーポレイテッド | 治療剤を含む治療用ナノ粒子とその製造方法および使用方法 |
CN104812381B (zh) | 2012-09-17 | 2018-01-26 | 辉瑞大药厂 | 用于制备治疗性纳米颗粒的方法 |
JP2016519091A (ja) * | 2013-03-18 | 2016-06-30 | ジェノシアンス ファルマ | 新規抗がん剤としてのキノリン誘導体 |
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