JP4759134B2 - ポリマー粒子ワクチンデリバリーシステム - Google Patents
ポリマー粒子ワクチンデリバリーシステム Download PDFInfo
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- JP4759134B2 JP4759134B2 JP2000543160A JP2000543160A JP4759134B2 JP 4759134 B2 JP4759134 B2 JP 4759134B2 JP 2000543160 A JP2000543160 A JP 2000543160A JP 2000543160 A JP2000543160 A JP 2000543160A JP 4759134 B2 JP4759134 B2 JP 4759134B2
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- B01D11/04—Solvent extraction of solutions which are liquid
- B01D11/0403—Solvent extraction of solutions which are liquid with a supercritical fluid
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| SE9801288A SE9801288D0 (sv) | 1998-04-14 | 1998-04-14 | Vaccine delivery system and metod of production |
| SE9801288-3 | 1998-04-14 | ||
| PCT/SE1999/000582 WO1999052550A1 (en) | 1998-04-14 | 1999-04-09 | Polymer particle vaccine delivery system |
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| US7582284B2 (en) | 2002-04-17 | 2009-09-01 | Nektar Therapeutics | Particulate materials |
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| US20060263350A1 (en) * | 2003-09-26 | 2006-11-23 | Fairfield Clinical Trials Llc | Combination antihistamine medication |
| SI21639A (sl) * | 2003-12-23 | 2005-06-30 | LEK farmacevtska dru�ba d.d. | Farmacevtski pripravek, ki vsebuje nemicelarne sulfobetaine |
| JP2008512350A (ja) * | 2004-07-01 | 2008-04-24 | イェール ユニバーシティ | 標的化され、そして高密度で薬物が負荷されるポリマー性物質 |
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| CA2996768C (en) | 2006-04-26 | 2020-12-08 | Micell Technologies, Inc. | Coatings containing multiple drugs |
| WO2008042909A2 (en) | 2006-10-02 | 2008-04-10 | Micell Technologies Inc. | Surgical sutures having increased strength |
| EP1913955A1 (en) | 2006-10-19 | 2008-04-23 | Gerhard, Markus | Novel method for treating H.pylori infections |
| CN101678388B (zh) * | 2006-10-23 | 2013-12-11 | 米歇尔技术公司 | 用于在涂覆过程中为基底充电的保持器 |
| CA2679712C (en) | 2007-01-08 | 2016-11-15 | Micell Technologies, Inc. | Stents having biodegradable layers |
| US11426494B2 (en) | 2007-01-08 | 2022-08-30 | MT Acquisition Holdings LLC | Stents having biodegradable layers |
| DK2425820T3 (en) | 2007-02-11 | 2015-07-13 | Map Pharmaceuticals Inc | A method for the therapeutic administration of DHE in order to enable quick relief of migraine, while minimizing the adverse event profile |
| US10265407B2 (en) | 2007-02-15 | 2019-04-23 | Yale University | Modular nanodevices for smart adaptable vaccines |
| BRPI0810370A2 (pt) * | 2007-04-17 | 2014-10-29 | Micell Technologies Inc | Stent revestido, e, método para preparar um stent |
| WO2008148013A1 (en) * | 2007-05-25 | 2008-12-04 | Micell Technologies, Inc. | Polymer films for medical device coating |
| US20100172845A1 (en) * | 2007-05-29 | 2010-07-08 | Board Of Regents Of The University Of Texas System | Compositions and methods for treating mycobacterial infections |
| CA2700808C (en) | 2007-09-27 | 2017-11-14 | Immunovaccine Technologies Inc. | Use of liposomes in a carrier comprising a continuous hydrophobic phase for delivery of polynucleotides in vivo |
| US20100209452A1 (en) * | 2007-10-03 | 2010-08-19 | Immunovaccine Technologies, Inc | Compositions comprising an antigen, an amphipathic compound and a hydrophobic carrier, and uses thereof |
| US20100298928A1 (en) * | 2007-10-19 | 2010-11-25 | Micell Technologies, Inc. | Drug Coated Stents |
| SG192523A1 (en) | 2008-04-17 | 2013-08-30 | Micell Technologies Inc | Stents having bioabsorbable layers |
| ES2524699T3 (es) * | 2008-06-05 | 2014-12-11 | Immunovaccine Technologies Inc. | Composiciones que comprenden liposomas, un antígeno, un polinucleótido y un vehículo que comprende una fase continua de una sustancia hidrófoba |
| US9510856B2 (en) | 2008-07-17 | 2016-12-06 | Micell Technologies, Inc. | Drug delivery medical device |
| EP2313122B1 (en) | 2008-07-17 | 2019-03-06 | Micell Technologies, Inc. | Drug delivery medical device |
| US8762067B2 (en) | 2008-10-31 | 2014-06-24 | The Invention Science Fund I, Llc | Methods and systems for ablation or abrasion with frozen particles and comparing tissue surface ablation or abrasion data to clinical outcome data |
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| US20100111857A1 (en) * | 2008-10-31 | 2010-05-06 | Boyden Edward S | Compositions and methods for surface abrasion with frozen particles |
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| US9072688B2 (en) | 2008-10-31 | 2015-07-07 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
| US20100111841A1 (en) * | 2008-10-31 | 2010-05-06 | Searete Llc | Compositions and methods for surface abrasion with frozen particles |
| US20100111836A1 (en) * | 2008-10-31 | 2010-05-06 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Compositions and methods for therapeutic delivery with frozen particles |
| US8485861B2 (en) * | 2008-10-31 | 2013-07-16 | The Invention Science Fund I, Llc | Systems, devices, and methods for making or administering frozen particles |
| US8788212B2 (en) | 2008-10-31 | 2014-07-22 | The Invention Science Fund I, Llc | Compositions and methods for biological remodeling with frozen particle compositions |
| US8545855B2 (en) * | 2008-10-31 | 2013-10-01 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
| US20100111835A1 (en) * | 2008-10-31 | 2010-05-06 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Compositions and methods for therapeutic delivery with frozen particles |
| US9072799B2 (en) * | 2008-10-31 | 2015-07-07 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
| US8793075B2 (en) * | 2008-10-31 | 2014-07-29 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
| US8409376B2 (en) | 2008-10-31 | 2013-04-02 | The Invention Science Fund I, Llc | Compositions and methods for surface abrasion with frozen particles |
| US8731840B2 (en) | 2008-10-31 | 2014-05-20 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
| US9050317B2 (en) * | 2008-10-31 | 2015-06-09 | The Invention Science Fund I, Llc | Compositions and methods for therapeutic delivery with frozen particles |
| US8834913B2 (en) * | 2008-12-26 | 2014-09-16 | Battelle Memorial Institute | Medical implants and methods of making medical implants |
| CA2756307C (en) * | 2009-03-23 | 2017-08-08 | Micell Technologies, Inc. | Peripheral stents having layers and reinforcement fibers |
| CA2756386C (en) * | 2009-03-23 | 2019-01-15 | Micell Technologies, Inc. | Drug delivery medical device |
| US20100256746A1 (en) * | 2009-03-23 | 2010-10-07 | Micell Technologies, Inc. | Biodegradable polymers |
| JP5464573B2 (ja) * | 2009-03-31 | 2014-04-09 | 独立行政法人産業技術総合研究所 | 中空粒子の製造方法 |
| WO2010120552A2 (en) * | 2009-04-01 | 2010-10-21 | Micell Technologies, Inc. | Coated stents |
| WO2010121187A2 (en) | 2009-04-17 | 2010-10-21 | Micell Techologies, Inc. | Stents having controlled elution |
| US9803060B2 (en) * | 2009-09-10 | 2017-10-31 | Bridgestone Corporation | Compositions and method for making hollow nanoparticles from metal soaps |
| US11369498B2 (en) | 2010-02-02 | 2022-06-28 | MT Acquisition Holdings LLC | Stent and stent delivery system with improved deliverability |
| US8795762B2 (en) | 2010-03-26 | 2014-08-05 | Battelle Memorial Institute | System and method for enhanced electrostatic deposition and surface coatings |
| JP2011207988A (ja) * | 2010-03-29 | 2011-10-20 | Sumitomo Chemical Co Ltd | 樹脂用の加工安定化剤、該加工安定化剤を含む樹脂組成物、および樹脂の加工安定性を向上させる方法 |
| CA2797110C (en) | 2010-04-22 | 2020-07-21 | Micell Technologies, Inc. | Stents and other devices having extracellular matrix coating |
| EP2593039B1 (en) | 2010-07-16 | 2022-11-30 | Micell Technologies, Inc. | Drug delivery medical device |
| US9821051B1 (en) | 2010-10-28 | 2017-11-21 | Seqirus UK Limited | Reducing hospitalization in elderly influenza vaccine recipients |
| MX350838B (es) | 2011-02-11 | 2017-09-18 | Grain Proc Corporation * | Composicion de sal. |
| KR20140041505A (ko) | 2011-04-29 | 2014-04-04 | 셀렉타 바이오사이언시즈, 인크. | 조절 b 세포 유도를 위한 관용원성 합성 나노운반체 |
| US10464100B2 (en) | 2011-05-31 | 2019-11-05 | Micell Technologies, Inc. | System and process for formation of a time-released, drug-eluting transferable coating |
| US10117972B2 (en) | 2011-07-15 | 2018-11-06 | Micell Technologies, Inc. | Drug delivery medical device |
| US20140356396A1 (en) * | 2011-08-25 | 2014-12-04 | Brian L. Pulliam | Rotavirus preparations with excess calcium ions and high viscosities that ensure viability at elevated temperatures |
| JP6240077B2 (ja) | 2011-10-06 | 2017-11-29 | イムノバクシーン・テクノロジーズ・インコーポレイテッドＩｍｍｕｎｏｖａｃｃｉｎｅ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｉｎｃ． | Ｔｌｒ２を活性化するか、またはその活性を増加させるアジュバントを含むリポソーム組成物およびその使用 |
| US10188772B2 (en) | 2011-10-18 | 2019-01-29 | Micell Technologies, Inc. | Drug delivery medical device |
| US9597385B2 (en) | 2012-04-23 | 2017-03-21 | Allertein Therapeutics, Llc | Nanoparticles for treatment of allergy |
| US8852648B2 (en) * | 2012-11-06 | 2014-10-07 | Rochal Industries, Llp | Delivery of biologically-active agents using volatile, hydrophobic solvents |
| AU2014248508B2 (en) | 2013-03-12 | 2018-11-08 | Micell Technologies, Inc. | Bioabsorbable biomedical implants |
| CN105188741A (zh) | 2013-04-03 | 2015-12-23 | 阿勒丁医疗公司 | 新型纳米颗粒组合物 |
| HUE052599T2 (hu) | 2013-05-03 | 2021-05-28 | Selecta Biosciences Inc | CD4+ szabályozó T-sejtek fokozására szolgáló eljárások és készítmények |
| WO2014186532A1 (en) | 2013-05-15 | 2014-11-20 | Micell Technologies, Inc. | Bioabsorbable biomedical implants |
| AU2015311704B2 (en) | 2014-09-07 | 2021-12-09 | Selecta Biosciences, Inc. | Methods and compositions for attenuating gene editing anti-viral transfer vector immune responses |
| ES2821761T3 (es) * | 2015-07-09 | 2021-04-27 | Evonik Operations Gmbh | Proceso de preparación de micropartículas de copolímero de poli(glicolida-co-lactida) |
| CA3007036A1 (en) | 2015-12-14 | 2017-06-22 | Technische Universitat Munchen | Helicobacter pylori vaccines |
| EP3272354A1 (en) | 2016-07-20 | 2018-01-24 | Technische Universität München | Agents and methods for the prevention or treatment of h. pylori infections |
| WO2018039465A1 (en) * | 2016-08-25 | 2018-03-01 | Selecta Biosciences, Inc. | Polyester polymer matrices for the delivery of allergens |
| WO2018169811A1 (en) | 2017-03-11 | 2018-09-20 | Selecta Biosciences, Inc. | Methods and compositions related to combined treatment with anti-inflammatories and synthetic nanocarriers comprising an immunosuppressant |
| KR102170146B1 (ko) * | 2019-03-05 | 2020-10-26 | 서울대학교산학협력단 | Pca 공정을 이용한 배양액의 결정화 장치 및 방법 |
| CN114207440A (zh) | 2019-06-04 | 2022-03-18 | 西莱克塔生物科技公司 | 聚乙二醇化尿酸酶的制剂和剂量 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996038475A1 (en) * | 1995-06-01 | 1996-12-05 | Astra Aktiebolag | Helicobacter pylori antigens and vaccine compositions |
| WO1997002810A2 (en) * | 1995-07-13 | 1997-01-30 | Danbiosyst Uk Limited | Polymeric lamellar substrate particles for drug delivery |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4038139A (en) * | 1976-07-16 | 1977-07-26 | G. D. Searle & Co., Limited | Cell culture medium |
| US4919929A (en) | 1984-02-01 | 1990-04-24 | Stolle Research & Development Corporation | Mammal immunization |
| JPS60100516A (ja) | 1983-11-04 | 1985-06-04 | Takeda Chem Ind Ltd | 徐放型マイクロカプセルの製造法 |
| US5417986A (en) * | 1984-03-16 | 1995-05-23 | The United States Of America As Represented By The Secretary Of The Army | Vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres |
| ATE61935T1 (de) | 1985-02-07 | 1991-04-15 | Takeda Chemical Industries Ltd | Verfahren zur herstellung von mikrokapseln. |
| US5075109A (en) * | 1986-10-24 | 1991-12-24 | Southern Research Institute | Method of potentiating an immune response |
| GB8919819D0 (en) | 1989-09-01 | 1989-10-18 | Coopers Animal Health | Complexes having adjuvant activity |
| US5622649A (en) | 1991-06-27 | 1997-04-22 | Emory University | Multiple emulsions and methods of preparation |
| AU2316892A (en) | 1991-06-27 | 1993-01-25 | Emory University | Multiple emulsions and methods of preparation |
| CH683149A5 (fr) * | 1991-07-22 | 1994-01-31 | Debio Rech Pharma Sa | Procédé pour la préparation de microsphères en matériau polymère biodégradable. |
| MX9301706A (es) * | 1992-04-13 | 1994-05-31 | Oravax Inc | Composicion de vacuna para el tratamiento de la infeccion por helicobacter. |
| ATE143803T1 (de) | 1992-12-22 | 1996-10-15 | Univ Cincinnati | Orale verabreichung von immunologischen aktiven biomolekülen und anderen therapeutischen proteinen |
| US5562909A (en) | 1993-07-12 | 1996-10-08 | Massachusetts Institute Of Technology | Phosphazene polyelectrolytes as immunoadjuvants |
| WO1995011010A1 (en) * | 1993-10-22 | 1995-04-27 | Genentech, Inc. | Methods and compositions for microencapsulation of antigens for use as vaccines |
| DE69415684T2 (de) | 1993-10-22 | 1999-06-10 | Genentech Inc., San Francisco, Calif. | Verfahren zur herstellung von mikrospharen mit einer wirbelschichtstufe |
| US5922253A (en) | 1995-05-18 | 1999-07-13 | Alkermes Controlled Therapeutics, Inc. | Production scale method of forming microparticles |
| KR0180334B1 (ko) * | 1995-09-21 | 1999-03-20 | 김윤 | 블럭 공중합체 미셀을 이용한 약물전달체 및 이에 약물을 봉입하는 방법 |
| US6042820A (en) | 1996-12-20 | 2000-03-28 | Connaught Laboratories Limited | Biodegradable copolymer containing α-hydroxy acid and α-amino acid units |
| WO1999003448A1 (en) * | 1997-07-14 | 1999-01-28 | The Board Of Trustees Of The University Of Illinois | Materials and methods for making improved micelle compositions |
| EP1227724B1 (de) * | 1999-10-26 | 2004-04-14 | Bayer CropScience GmbH | Herbizide mittel |
| US6521736B2 (en) * | 2000-09-15 | 2003-02-18 | University Of Massachusetts | Amphiphilic polymeric materials |
-
1998
- 1998-04-14 SE SE9801288A patent/SE9801288D0/xx unknown
-
1999
- 1999-04-09 EP EP99924075A patent/EP1071457B1/en not_active Expired - Lifetime
- 1999-04-09 AT AT99924075T patent/ATE545432T1/de active
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- 1999-04-09 WO PCT/SE1999/000582 patent/WO1999052550A1/en not_active Ceased
- 1999-04-09 JP JP2000543160A patent/JP4759134B2/ja not_active Expired - Fee Related
-
2011
- 2011-01-07 JP JP2011001576A patent/JP2011140491A/ja not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996038475A1 (en) * | 1995-06-01 | 1996-12-05 | Astra Aktiebolag | Helicobacter pylori antigens and vaccine compositions |
| WO1997002810A2 (en) * | 1995-07-13 | 1997-01-30 | Danbiosyst Uk Limited | Polymeric lamellar substrate particles for drug delivery |
Also Published As
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|---|---|
| JP2011140491A (ja) | 2011-07-21 |
| US6838089B1 (en) | 2005-01-04 |
| WO1999052550A1 (en) | 1999-10-21 |
| SE9801288D0 (sv) | 1998-04-14 |
| AU4066299A (en) | 1999-11-01 |
| JP2002516822A (ja) | 2002-06-11 |
| AU765118B2 (en) | 2003-09-11 |
| EP1071457A1 (en) | 2001-01-31 |
| EP1071457B1 (en) | 2012-02-15 |
| ATE545432T1 (de) | 2012-03-15 |
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