JP2006514698A5 - - Google Patents
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- JP2006514698A5 JP2006514698A5 JP2005510834A JP2005510834A JP2006514698A5 JP 2006514698 A5 JP2006514698 A5 JP 2006514698A5 JP 2005510834 A JP2005510834 A JP 2005510834A JP 2005510834 A JP2005510834 A JP 2005510834A JP 2006514698 A5 JP2006514698 A5 JP 2006514698A5
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- Prior art keywords
- solvent
- drug
- particles
- paclitaxel
- polymer
- Prior art date
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| CA2447990C (en) * | 2001-05-31 | 2012-01-31 | Skyepharma Inc. | Encapsulation of nanosuspensions in liposomes and microspheres |
| US7767249B2 (en) * | 2001-06-07 | 2010-08-03 | Hewlett-Packard Development Company, L.P. | Preparation of nanoparticles |
| US20050271737A1 (en) * | 2001-06-07 | 2005-12-08 | Chinea Vanessa I | Application of a bioactive agent to a substrate |
| EP1401399A2 (en) * | 2001-06-22 | 2004-03-31 | Pfizer Products Inc. | Pharmaceutical compositions containing polymer and drug assemblies |
| GB0311081D0 (en) | 2003-05-14 | 2003-06-18 | Btg Internat Limted | Treatment of neurodegenerative conditions |
| ES2232287B1 (es) * | 2003-07-04 | 2006-11-01 | Advanced In Vitro Cell Technologies, S.L. | Nanoparticulas de derivados polioxietilenados. |
| WO2005018632A1 (en) | 2003-08-18 | 2005-03-03 | Btg International Limited | Treatment of neurodegenerative conditions |
| US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
| US8377952B2 (en) | 2003-08-28 | 2013-02-19 | Abbott Laboratories | Solid pharmaceutical dosage formulation |
| EP1824458A1 (en) * | 2004-11-18 | 2007-08-29 | Bristol-Myers Squibb Company | Enteric coated bead comprising epothilone or an epothilone analog, and preparation and administration thereof |
| JP2008531591A (ja) * | 2005-02-24 | 2008-08-14 | エラン・ファルマ・インターナショナル・リミテッド | ドセタキセルおよびそれらの類似体のナノ粒子製剤 |
| WO2006093066A1 (ja) * | 2005-02-28 | 2006-09-08 | Hisamitsu Pharmaceutical Co., Inc. | 粘着基材及び該粘着基材を含む医療用貼付製剤 |
| GB0504362D0 (en) | 2005-03-02 | 2005-04-06 | Btg Int Ltd | Cytokine modulators |
| BRPI0614455A2 (pt) | 2005-07-28 | 2011-03-29 | Isp Investments Inc | efavirenz amorfo e a produção deste |
| US8529537B2 (en) * | 2005-08-05 | 2013-09-10 | Kimberly-Clark Worldwide, Inc. | Absorbent article with enclosures |
| US20070098802A1 (en) * | 2005-10-31 | 2007-05-03 | Isaac Farr | Organic nanoparticles and associated methods |
| EP2037888A2 (en) * | 2006-06-26 | 2009-03-25 | Mutual Pharmaceutical Company, Inc. | Active agent formulations, methods of making, and methods of use |
| GB0613925D0 (en) * | 2006-07-13 | 2006-08-23 | Unilever Plc | Improvements relating to nanodispersions |
| US8242165B2 (en) * | 2006-10-26 | 2012-08-14 | Creighton University | Mucoadhesive nanoparticles for cancer treatment |
| WO2008080037A2 (en) | 2006-12-21 | 2008-07-03 | Isp Investments Inc. | Carotenoids of enhanced bioavailability |
| CN101622302B (zh) | 2007-01-26 | 2013-01-23 | Isp投资公司 | 生产喷雾干燥产品的制剂工艺方法 |
| CA2683777C (en) * | 2007-04-13 | 2016-08-23 | University Of North Texas Health Science Center At Fort Worth | Formulation of active agent loaded activated plga nanoparticles for targeted cancer nano-therapeutics |
| US20100290982A1 (en) * | 2007-04-13 | 2010-11-18 | University Of North Texas Health Science Center At Fort Worth | Solid in oil/water emulsion-diffusion-evaporation formulation for preparing curcumin-loaded plga nanoparticles |
| US8309129B2 (en) | 2007-05-03 | 2012-11-13 | Bend Research, Inc. | Nanoparticles comprising a drug, ethylcellulose, and a bile salt |
| WO2008135855A2 (en) | 2007-05-03 | 2008-11-13 | Pfizer Products Inc. | Nanoparticles comprising a cholesteryl ester transfer protein inhibitor and a nonionizable polymer |
| US9545384B2 (en) | 2007-06-04 | 2017-01-17 | Bend Research, Inc. | Nanoparticles comprising drug, a non-ionizable cellulosic polymer and tocopheryl polyethylene glocol succinate |
| EP2162120B1 (en) | 2007-06-04 | 2016-05-04 | Bend Research, Inc | Nanoparticles comprising a non-ionizable cellulosic polymer and an amphiphilic non-ionizable block copolymer |
| US20090087460A1 (en) * | 2007-10-02 | 2009-04-02 | Hamamatsu Photonics K.K. | Solid composition, microparticles, microparticle dispersion liquid, and manufacturing methods for these |
| WO2009052491A2 (en) * | 2007-10-18 | 2009-04-23 | Geraghty, Erin | Fenoldopam formulations and prodrug derivatives |
| EP2231169B1 (en) | 2007-12-06 | 2016-05-04 | Bend Research, Inc. | Pharmaceutical compositions comprising nanoparticles and a resuspending material |
| WO2009073216A1 (en) | 2007-12-06 | 2009-06-11 | Bend Research, Inc. | Nanoparticles comprising a non-ionizable polymer and an amine-functionalized methacrylate copolymer |
| US8614057B2 (en) * | 2008-06-12 | 2013-12-24 | The Invention Science Fund I, Llc | Methods for collecting and detecting oligonucleotides |
| US8252529B2 (en) * | 2008-06-12 | 2012-08-28 | The Invention Science Fund I, Llc | Methods for collecting and detecting oligonucleotides |
| US8252528B2 (en) * | 2008-06-12 | 2012-08-28 | The Invention Science Fund I, Llc | Methods, compositions, and kits for collecting and detecting oligonucleotides |
| GB0810990D0 (en) * | 2008-06-16 | 2008-07-23 | Q Chip Ltd | Device and method of making solid beads |
| WO2010005726A2 (en) | 2008-06-16 | 2010-01-14 | Bind Biosciences Inc. | Therapeutic polymeric nanoparticles with mtor inhibitors and methods of making and using same |
| AU2009268923B2 (en) | 2008-06-16 | 2015-09-17 | Pfizer Inc. | Drug loaded polymeric nanoparticles and methods of making and using same |
| 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 |
| WO2010068866A2 (en) * | 2008-12-12 | 2010-06-17 | Bind Biosciences | Therapeutic particles suitable for parenteral administration and methods of making and using same |
| JP2012512175A (ja) * | 2008-12-15 | 2012-05-31 | バインド バイオサイエンシズ インコーポレイテッド | 治療薬を徐放するための長時間循環性ナノ粒子 |
| US20100159010A1 (en) * | 2008-12-24 | 2010-06-24 | Mutual Pharmaceutical Company, Inc. | Active Agent Formulations, Methods of Making, and Methods of Use |
| JPWO2010137335A1 (ja) * | 2009-05-29 | 2012-11-12 | 江崎グリコ株式会社 | α−リポ酸ナノ粒子を含有する、ターンオーバー促進用組成物 |
| EP2509634B1 (en) | 2009-12-11 | 2019-03-06 | Pfizer Inc | Stable formulations for lyophilizing therapeutic particles |
| WO2011084513A2 (en) | 2009-12-15 | 2011-07-14 | Bind Biosciences, Inc. | Therapeutic polymeric nanoparticle compositions with high glass transition temperature or high molecular weight copolymers |
| AP3552A (en) | 2010-05-03 | 2016-01-18 | Teikoku Pharma Usa Inc | Non-aqueous taxane pro-emulsion formulations and methods of making and using the same |
| US8652366B2 (en) * | 2010-11-01 | 2014-02-18 | Board Of Regents, The University Of Texas System | Aerosol-mediated particle synthesis |
| US9687569B2 (en) | 2012-08-16 | 2017-06-27 | University Of Washington Through Its Center For Commercialization | Theranostic nanoparticle and methods for making and using the nanoparticle |
| NZ705812A (en) | 2012-09-17 | 2018-08-31 | Pfizer | Process for preparing therapeutic nanoparticles |
| JO3685B1 (ar) | 2012-10-01 | 2020-08-27 | Teikoku Pharma Usa Inc | صيغ التشتيت الجسيمي للتاكسين غير المائي وطرق استخدامها |
| SG10201705514WA (en) * | 2012-12-28 | 2017-08-30 | Tarveda Therapeutics Inc | Targeted conjugates encapsulated in particles and formulations thereof |
| MY178189A (en) | 2014-03-14 | 2020-10-06 | Pfizer | Therapeutic nanoparticles comprising a therapeutic agent and methods of making and using same |
| US9874554B1 (en) * | 2014-07-16 | 2018-01-23 | Verily Life Sciences Llc | Aptamer-based in vivo diagnostic system |
| EP3302431B1 (en) * | 2015-06-04 | 2020-11-11 | Crititech, Inc. | Taxane particles and their use |
| CN108778244B (zh) | 2015-09-16 | 2022-04-01 | Dfb索里亚有限责任公司 | 药物纳米颗粒的递送及其使用方法 |
| US10548881B2 (en) | 2016-02-23 | 2020-02-04 | Tarveda Therapeutics, Inc. | HSP90 targeted conjugates and particles and formulations thereof |
| AU2017243601A1 (en) * | 2016-03-30 | 2018-11-22 | Acib Gmbh | Detecting microbial infection in wounds |
| BR112018069628A2 (pt) | 2016-04-04 | 2019-02-12 | Crititech, Inc. | métodos para tratamento de tumor sólido |
| WO2018170196A1 (en) | 2017-03-15 | 2018-09-20 | Dfb Soria, Llc | Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes |
| WO2018227037A1 (en) | 2017-06-09 | 2018-12-13 | Crititech, Inc. | Treatment of epithelial cysts by intracystic injection of antineoplastic particles |
| CA3063436A1 (en) | 2017-06-14 | 2018-12-20 | Crititech, Inc. | Methods for treating lung disorders |
| CA3076919A1 (en) | 2017-10-03 | 2019-04-11 | Crititech, Inc. | Local delivery of antineoplastic particles in combination with systemic delivery of immunotherapeutic agents for the treatment of cancer |
| US11389545B2 (en) * | 2018-01-09 | 2022-07-19 | Aqua Regenerative Therapies Llc | Bioactive nanoparticles and methods for making same |
| JP2021512860A (ja) | 2018-02-01 | 2021-05-20 | コーバス・ファーマシューティカルズ・インコーポレイテッド | 薬学的製剤 |
| US11497726B2 (en) | 2018-03-16 | 2022-11-15 | Dfb Soria, Ll. | Topical therapy for the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer using nanoparticles of taxanes |
| CN111249476B (zh) * | 2020-02-19 | 2023-09-26 | 深圳厚存纳米药业有限公司 | 泊洛沙姆和/或泊洛沙胺与脂质组合中性复合物纳米粒 |
| CN114983976B (zh) * | 2022-06-23 | 2023-07-25 | 浙江工业大学 | 一种紫杉醇纳米制剂及其制备方法和应用 |
| WO2024011218A1 (en) * | 2022-07-08 | 2024-01-11 | Brown University | Polymeric nanoparticles for long acting delivery of a peptide and methods of making and using thereof |
| WO2024226846A2 (en) | 2023-04-26 | 2024-10-31 | Vivtex Corporation | Formulation of therapeutic agents for improved permeation |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4757128A (en) * | 1986-08-01 | 1988-07-12 | Massachusetts Institute Of Technology | High molecular weight polyanhydride and preparation thereof |
| US4861627A (en) * | 1987-05-01 | 1989-08-29 | Massachusetts Institute Of Technology | Preparation of multiwall polymeric microcapsules |
| US5985354A (en) * | 1995-06-07 | 1999-11-16 | Brown University Research Foundation | Preparation of multiwall polymeric microcapsules from hydrophilic polymers |
| US5000886A (en) * | 1987-05-26 | 1991-03-19 | American Cyanamid Company | Silicone-hardened pharmaceutical microcapsules and process of making the same |
| US4997904A (en) * | 1989-08-25 | 1991-03-05 | Nova Pharmaceutical Corporation | Aromatic polyanhydride compositions |
| US5271961A (en) * | 1989-11-06 | 1993-12-21 | Alkermes Controlled Therapeutics, Inc. | Method for producing protein microspheres |
| US5175235A (en) * | 1990-06-04 | 1992-12-29 | Nova Pharmaceutical Corporation | Branched polyanhydrides |
| US6197346B1 (en) * | 1992-04-24 | 2001-03-06 | Brown Universtiy Research Foundation | Bioadhesive microspheres and their use as drug delivery and imaging systems |
| US6235313B1 (en) * | 1992-04-24 | 2001-05-22 | Brown University Research Foundation | Bioadhesive microspheres and their use as drug delivery and imaging systems |
| US5916596A (en) * | 1993-02-22 | 1999-06-29 | Vivorx Pharmaceuticals, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
| WO1995024929A2 (en) * | 1994-03-15 | 1995-09-21 | Brown University Research Foundation | Polymeric gene delivery system |
| US6143211A (en) * | 1995-07-21 | 2000-11-07 | Brown University Foundation | Process for preparing microparticles through phase inversion phenomena |
| EP0840623B1 (en) * | 1995-07-21 | 2007-07-18 | Brown University Research Foundation | Compositions for gene therapy comprising nucleic acid loaded polymeric microparticles |
| US6245805B1 (en) * | 1995-10-26 | 2001-06-12 | Baker Norton Pharmaceuticals, Inc. | Method, compositions and kits for increasing the oral bioavailability of pharmaceutical agents |
| US5968972A (en) * | 1995-10-26 | 1999-10-19 | Baker Norton Pharmaceuticals, Inc. | Method for increasing the oral bioactivity of pharmaceutical agents |
| US5955096A (en) * | 1996-06-25 | 1999-09-21 | Brown University Research Foundation | Methods and compositions for enhancing the bioadhesive properties of polymers using organic excipients |
| KR20010005740A (ko) * | 1997-03-27 | 2001-01-15 | 아이박스 코포레이션 | 난소암 치료를 위한 방법과 조성물 |
| JP2003512443A (ja) * | 1999-10-27 | 2003-04-02 | ベーカー ノートン ファーマシューティカルズ インコーポレイテッド | タキサンをヒト患者に経口投与するための方法及び組成物 |
| FR2806005B1 (fr) * | 2000-03-10 | 2002-06-14 | Univ Claude Bernard Lyon | Procede de preparation de particules colloidales sous forme de nanocapsules |
| WO2002003957A2 (en) * | 2000-07-07 | 2002-01-17 | Guilford Pharmaceuticals, Inc. | Compositions for sustained release of antineoplastic taxanes, and methods of making and using the same |
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2003
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- 2003-10-30 EP EP03816481A patent/EP1569620A4/en not_active Withdrawn
- 2003-10-30 AU AU2003304108A patent/AU2003304108B2/en not_active Ceased
- 2003-10-30 JP JP2005510834A patent/JP2006514698A/ja active Pending
- 2003-10-30 CA CA002504268A patent/CA2504268A1/en not_active Abandoned
- 2003-10-30 US US10/696,829 patent/US20040220081A1/en not_active Abandoned
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