CA2250219C - Materials and methods for making improved liposome compositions - Google Patents
Materials and methods for making improved liposome compositions Download PDFInfo
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- CA2250219C CA2250219C CA002250219A CA2250219A CA2250219C CA 2250219 C CA2250219 C CA 2250219C CA 002250219 A CA002250219 A CA 002250219A CA 2250219 A CA2250219 A CA 2250219A CA 2250219 C CA2250219 C CA 2250219C
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- liposomes
- vip
- liposome
- biologically active
- peptide
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| US6056973A (en) * | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
| US20050025819A1 (en) * | 1997-07-14 | 2005-02-03 | Hayat Onyuksel | Materials and methods for making improved micelle compositions |
| US20020115609A1 (en) * | 1997-07-14 | 2002-08-22 | Hayat Onyuksel | Materials and methods for making improved micelle compositions |
| US6217886B1 (en) * | 1997-07-14 | 2001-04-17 | The Board Of Trustees Of The University Of Illinois | Materials and methods for making improved micelle compositions |
| ES2384094T3 (es) | 1997-11-14 | 2012-06-29 | Pacira Pharmaceuticals, Inc. | Producción de liposomas multivesiculares |
| DE19813773A1 (de) * | 1998-03-27 | 1999-09-30 | Clemens Unger | Verfahren zur Herstellung von liposomalen Wirkstoffformulierungen |
| GB9813100D0 (en) * | 1998-06-18 | 1998-08-19 | Secr Defence | Method of forming liposomes |
| US20020114829A1 (en) * | 1998-12-18 | 2002-08-22 | Hayat Onyuksel | Materials and methods for making improved liposome compositions |
| JP2003501631A (ja) * | 1999-05-27 | 2003-01-14 | ツェプトゼンス アクチエンゲゼルシャフト | 官能基化された小胞 |
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| US7223406B2 (en) * | 2000-07-21 | 2007-05-29 | The Regents Of The University Of California | Methods and compositions for preventing and treating male erectile dysfunction and female sexual arousal disorder |
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| FR2825273B1 (fr) * | 2001-05-29 | 2006-11-24 | Oreal | Composition pour le traitement des signes cutanes du vieillissement |
| EP2075256A2 (en) | 2002-01-14 | 2009-07-01 | William Herman | Multispecific binding molecules |
| CA2368656A1 (en) * | 2002-01-21 | 2003-07-21 | Vasogen Ireland Limited | Receptor-ligand pairing for anti-inflammatory response |
| JP4632664B2 (ja) | 2002-02-13 | 2011-02-16 | デューク ユニバーシティ | 非ペプチド結合ストレス応答性ポリペプチドによる免疫応答の調節 |
| US20030180348A1 (en) * | 2002-03-22 | 2003-09-25 | Levinson R. Saul | Transcellular drug delivery system |
| WO2003082303A1 (en) * | 2002-03-29 | 2003-10-09 | Wisconsin Alumni Research Foundation | Polymeric micelle formulations of hydrophobic compounds and methods |
| US20030219696A1 (en) * | 2002-05-23 | 2003-11-27 | Moreland Gerald W. | Method and apparatus for preventing backflow in dental saliva evacuators |
| US20060241028A1 (en) | 2002-06-10 | 2006-10-26 | Dorian Bevec | Use of compounds having the biological activity of vasoactive intestinal peptide for the treatment of sarcoidosis |
| US20060128615A1 (en) * | 2002-09-18 | 2006-06-15 | Pierrette Gaudreau | Ghrh analogues |
| JP2004115397A (ja) * | 2002-09-25 | 2004-04-15 | Fuji Photo Film Co Ltd | 血管疾患治療薬を含むリポソーム |
| US7785623B2 (en) * | 2002-10-01 | 2010-08-31 | Keller Brian C | Compositions and methods useful for the reduction of fine lines and wrinkles |
| US7655618B2 (en) * | 2002-12-27 | 2010-02-02 | Diobex, Inc. | Compositions and methods for the prevention and control of insulin-induced hypoglycemia |
| EP1578437A4 (en) * | 2002-12-27 | 2006-08-09 | Diobex Inc | COMPOSITIONS AND METHODS FOR PREVENTING AND REDUCING INSULIN-INDUCED HYPOGLYCEMIA |
| US11324698B2 (en) | 2003-08-28 | 2022-05-10 | Vgsk Technologies, Inc. | Sterically stabilized carrier for aerosol therapeutics, compositions and methods for treating the respiratory tract of a mammal |
| US20060115523A1 (en) * | 2004-12-01 | 2006-06-01 | Konduri Kameswari S | Sterically stabilized liposome and triamcinolone composition for treating the respiratory tract of a mammal |
| US8846079B1 (en) | 2004-12-01 | 2014-09-30 | Vgsk Technologies, Inc. | Sterically stabilized carrier for aerosol therapeutics, compositions and methods for treating the respiratory tract of a mammal |
| US20060251711A1 (en) * | 2003-08-28 | 2006-11-09 | Vgsk Technologies, Inc. | Sterically stabilized carrier for aerosol therapeutics, compositions and methods for treating diseases of the respiratory tract of a mammal |
| US6911430B2 (en) * | 2003-10-01 | 2005-06-28 | Vipogen, Llc | Compositions and methods for treating ileus |
| JP2005170923A (ja) * | 2003-10-21 | 2005-06-30 | Konica Minolta Medical & Graphic Inc | リポソーム含有ｘ線造影剤およびその製造方法 |
| JP2005170928A (ja) * | 2003-10-21 | 2005-06-30 | Konica Minolta Medical & Graphic Inc | リポソーム含有ｘ線造影剤およびその製造方法 |
| JP4654590B2 (ja) * | 2004-03-31 | 2011-03-23 | コニカミノルタエムジー株式会社 | Ｘ線ｃｔ用造影組成物およびその製造方法 |
| US6998028B1 (en) * | 2004-09-24 | 2006-02-14 | Superpower, Inc. | Methods for forming superconducting conductors |
| JP2006248978A (ja) * | 2005-03-10 | 2006-09-21 | Mebiopharm Co Ltd | 新規なリポソーム製剤 |
| ES2798263T3 (es) | 2005-12-08 | 2020-12-10 | Insmed Inc | Composiciones a base de lípidos de antiinfecciosos para tratar infecciones pulmonares |
| US8071127B2 (en) * | 2006-10-24 | 2011-12-06 | Aradigm Corporation | Dual action, inhaled formulations providing both an immediate and sustained release profile |
| US8119156B2 (en) | 2006-10-24 | 2012-02-21 | Aradigm Corporation | Dual action, inhaled formulations providing both an immediate and sustained release profile |
| US8268347B1 (en) | 2006-10-24 | 2012-09-18 | Aradigm Corporation | Dual action, inhaled formulations providing both an immediate and sustained release profile |
| US9119783B2 (en) | 2007-05-07 | 2015-09-01 | Insmed Incorporated | Method of treating pulmonary disorders with liposomal amikacin formulations |
| US20100210575A1 (en) * | 2007-06-29 | 2010-08-19 | Wisconsin Alumni Research Foundation | Structuring effect of cholesterol in peg-phospholipid micelles, drug delivery of amphotericin b, and combination antifungals |
| JP5491511B2 (ja) * | 2008-10-07 | 2014-05-14 | ブラッコ・シュイス・ソシエテ・アノニム | 抗ポリマー抗体およびそれと結合するリポソームまたは微小胞を含むターゲッティング構築物 |
| EP2184054A1 (en) * | 2008-11-08 | 2010-05-12 | Lipoxen Technologies Limited | Small Interfering RNA Delivery |
| US20110158903A1 (en) * | 2009-12-31 | 2011-06-30 | Institute Of Nuclear Energy Research Atomic Energy Council, Executive Yuan | One pot processes of preparing multifunctional liposome drug for imaging, delivery and targeting in cancer diagnosis and therapy |
| JP6347743B2 (ja) * | 2011-05-05 | 2018-06-27 | マティナス バイオファーマ ナノテクノロジーズ，インコーポレーテッド | コクリエート組成物およびその製造および使用方法 |
| MX2015006681A (es) | 2012-11-29 | 2016-04-06 | Insmed Inc | Formulaciones de vancomicina estabilizadas. |
| CN110237270A (zh) | 2013-03-15 | 2019-09-17 | 洛马林达大学 | 自身免疫性疾病的治疗 |
| MX2016005232A (es) | 2013-10-22 | 2017-01-19 | Aradigm Corp | Formulaciones liposomicas para inhalacion, modificadas con agente tensoactivo, que proveen un perfil de liberacion tanto inmediata como sostenida. |
| ES2755941T3 (es) | 2014-05-15 | 2020-04-24 | Insmed Inc | Métodos para tratar infecciones pulmonares micobacterianas no tuberculosas |
| US10987048B2 (en) | 2014-08-13 | 2021-04-27 | Elwha Llc | Systems, methods, and devices to incentivize inhaler use |
| US10765817B2 (en) | 2014-08-13 | 2020-09-08 | Elwha, Llc | Methods, systems, and devices related to delivery of alcohol with an inhaler |
| US10245393B2 (en) | 2014-08-13 | 2019-04-02 | Elwha Llc | Methods, systems, and devices related to a supplemental inhaler |
| CA2997286A1 (en) | 2015-09-14 | 2017-03-23 | Vgsk Technologies, Inc. | A sterically stabilized carrier for subcutaneous, sublingual and oral therapeutics, compositions and methods for treating a mammal |
| US9836646B2 (en) * | 2015-10-15 | 2017-12-05 | I.R.I.S. | Method for identifying a character in a digital image |
| US11339209B2 (en) | 2016-11-14 | 2022-05-24 | Novartis Ag | Compositions, methods, and therapeutic uses related to fusogenic protein minion |
| WO2019191627A1 (en) | 2018-03-30 | 2019-10-03 | Insmed Incorporated | Methods for continuous manufacture of liposomal drug products |
| US11788091B2 (en) | 2019-08-21 | 2023-10-17 | University Of Virginia Patent Foundation | Methods and compositions for diagnosing and treating prostate cancer based on long noncoding RNA overlapping the LCK gene that regulates prostate cancer cell growth |
| US12319967B2 (en) | 2019-08-21 | 2025-06-03 | University Of Virginia Patent Foundation | Methods and compositions for diagnosing and treating prostate cancer based on long noncoding RNA overlapping the LCK gene that regulates prostate cancer cell growth |
| US11033495B1 (en) | 2021-01-22 | 2021-06-15 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12151024B2 (en) | 2021-01-22 | 2024-11-26 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US11278494B1 (en) | 2021-01-22 | 2022-03-22 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US11357727B1 (en) | 2021-01-22 | 2022-06-14 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| AU2022270670A1 (en) | 2021-05-05 | 2023-11-30 | Nejat Duzgunes | Liposome-encapsulated corticosteriods inhibit sars-cov-2 replication and reduces lung inflammation |
| WO2023064464A1 (en) | 2021-10-14 | 2023-04-20 | Pacira Pharmaceuticals, Inc. | Bupivacaine multivesicular liposome formulations and uses thereof |
| US12251472B1 (en) | 2024-05-20 | 2025-03-18 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12156940B1 (en) | 2024-05-20 | 2024-12-03 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12280149B1 (en) | 2024-05-20 | 2025-04-22 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4529561A (en) * | 1978-03-24 | 1985-07-16 | The Regents Of The University Of California | Method for producing liposomes in selected size range |
| JPS5782311A (en) | 1980-11-11 | 1982-05-22 | Tanabe Seiyaku Co Ltd | Production of liposome preparation |
| US5374548A (en) * | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
| US4920016A (en) | 1986-12-24 | 1990-04-24 | Linear Technology, Inc. | Liposomes with enhanced circulation time |
| ZA896668B (en) | 1988-09-01 | 1990-06-27 | Molecular Therapeutics Inc | A human rhinovirus receptor protein that inhibits virus infectivity |
| US5225212A (en) | 1989-10-20 | 1993-07-06 | Liposome Technology, Inc. | Microreservoir liposome composition and method |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5585112A (en) | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
| US5542935A (en) | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
| US5230882A (en) | 1989-12-22 | 1993-07-27 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
| US5580575A (en) | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
| US5543390A (en) | 1990-11-01 | 1996-08-06 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University | Covalent microparticle-drug conjugates for biological targeting |
| CA2108266C (en) | 1991-04-19 | 2003-06-03 | Albert J. Owen | Convertible microemulsion formulations |
| US5573934A (en) | 1992-04-20 | 1996-11-12 | Board Of Regents, The University Of Texas System | Gels for encapsulation of biological materials |
| WO1993020802A1 (en) | 1992-04-09 | 1993-10-28 | Northwestern University | Acoustically reflective liposomes and methods to make and use the same |
| US5552156A (en) | 1992-10-23 | 1996-09-03 | Ohio State University | Liposomal and micellular stabilization of camptothecin drugs |
| US5595722A (en) | 1993-01-28 | 1997-01-21 | Neorx Corporation | Method for identifying an agent which increases TGF-beta levels |
| EP0688429B1 (en) | 1993-03-09 | 1998-02-11 | Epic Therapeutics, Inc.. | Macromolecular microparticles and methods of production |
| CA2162586C (en) | 1993-05-13 | 2006-01-03 | David J. Grainger | Prevention and treatment of pathologies associated with abnormally proliferative smooth muscle cells |
| US5534241A (en) | 1993-07-23 | 1996-07-09 | Torchilin; Vladimir P. | Amphipathic polychelating compounds and methods of use |
| US5514670A (en) | 1993-08-13 | 1996-05-07 | Pharmos Corporation | Submicron emulsions for delivery of peptides |
| US5759548A (en) | 1993-11-30 | 1998-06-02 | Lxr Biotechnology Inc. | Compositions which inhibit apoptosis, methods of purifying the compositions and uses thereof |
| US5540935A (en) | 1993-12-06 | 1996-07-30 | Nof Corporation | Reactive vesicle and functional substance-fixed vesicle |
| US5580853A (en) | 1994-03-22 | 1996-12-03 | New England Deaconess Hospital | Modified polypeptides with increased biological activity |
| AU709559B2 (en) | 1994-04-07 | 1999-09-02 | Proteinix Company | Vasoactive intestinal polypeptide |
| US5567410A (en) | 1994-06-24 | 1996-10-22 | The General Hospital Corporation | Composotions and methods for radiographic imaging |
| US5587149A (en) | 1995-02-06 | 1996-12-24 | R.P. Scherer Corporation | Topical application emulsions |
| US5612027A (en) | 1995-04-18 | 1997-03-18 | Galin; Miles A. | Controlled release of miotic and mydriatic drugs in the anterior chamber |
| CA2250219C (en) | 1996-03-28 | 2008-10-07 | Hayat Onyuksel | Materials and methods for making improved liposome compositions |
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| EP0914094A1 (en) | 1999-05-12 |
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