CA2449439A1 - Particles for inhalation having rapid release properties - Google Patents
Particles for inhalation having rapid release properties Download PDFInfo
- Publication number
- CA2449439A1 CA2449439A1 CA002449439A CA2449439A CA2449439A1 CA 2449439 A1 CA2449439 A1 CA 2449439A1 CA 002449439 A CA002449439 A CA 002449439A CA 2449439 A CA2449439 A CA 2449439A CA 2449439 A1 CA2449439 A1 CA 2449439A1
- Authority
- CA
- Canada
- Prior art keywords
- particles
- insulin
- dppc
- sodium citrate
- weight
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
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Classifications
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
- A61K47/544—Phospholipids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
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- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Charge And Discharge Circuits For Batteries Or The Like (AREA)
- Electric Propulsion And Braking For Vehicles (AREA)
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| US09/888,126 US20020141946A1 (en) | 2000-12-29 | 2001-06-22 | Particles for inhalation having rapid release properties |
| US09/888,126 | 2001-06-22 | ||
| PCT/US2002/020280 WO2003000202A2 (en) | 2001-06-22 | 2002-06-24 | Particles for inhalation having rapid release properties |
Publications (1)
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| CA2449439A1 true CA2449439A1 (en) | 2003-01-03 |
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Families Citing this family (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060171899A1 (en) * | 1998-12-10 | 2006-08-03 | Akwete Adjei | Water-stabilized aerosol formulation system and method of making |
| US9006175B2 (en) | 1999-06-29 | 2015-04-14 | Mannkind Corporation | Potentiation of glucose elimination |
| US7575761B2 (en) | 2000-06-30 | 2009-08-18 | Novartis Pharma Ag | Spray drying process control of drying kinetics |
| WO2003024396A2 (en) * | 2001-09-17 | 2003-03-27 | Glaxo Group Limited | Dry powder medicament formulations |
| TW200300696A (en) | 2001-11-01 | 2003-06-16 | Inhale Therapeutic Syst | Spray drying methods and related compositions |
| AU2003220125B2 (en) | 2002-03-20 | 2006-06-15 | Mannkind Corporation | Inhalation apparatus |
| US7008644B2 (en) | 2002-03-20 | 2006-03-07 | Advanced Inhalation Research, Inc. | Method and apparatus for producing dry particles |
| US9339459B2 (en) | 2003-04-24 | 2016-05-17 | Nektar Therapeutics | Particulate materials |
| MXPA05012821A (es) * | 2003-05-28 | 2006-02-13 | Nektar Therapeutics | Formulacion farmaceutica que comprende un agente activo insoluble en agua. |
| WO2005032483A2 (en) * | 2003-10-01 | 2005-04-14 | Momenta Pharmaceuticals, Inc. | Polysaccharides for pulmonary delivery of active agents |
| US20050107959A1 (en) * | 2003-10-03 | 2005-05-19 | Yuanpeng Zhang | Screening method for evaluation of bilayer-drug interaction in liposomal compositions |
| US20050191360A1 (en) * | 2004-02-10 | 2005-09-01 | Advanced Inhalation Research, Inc. | Particles for inhalation having rapid release properties |
| PL1786784T3 (pl) | 2004-08-20 | 2011-04-29 | Mannkind Corp | Kataliza syntezy diketopiperazyn |
| EP2314298B1 (en) | 2004-08-23 | 2015-05-27 | MannKind Corporation | Microparticles comprising diketopiperazine salts for drug delivery |
| AU2006290870B2 (en) | 2005-09-14 | 2013-02-28 | Mannkind Corporation | Method of drug formulation based on increasing the affinity of active agents for crystalline microparticle surfaces |
| US20070123449A1 (en) * | 2005-11-01 | 2007-05-31 | Advanced Inhalation Research, Inc. | High load particles for inhalation having rapid release properties |
| US20070172430A1 (en) * | 2006-01-20 | 2007-07-26 | Nastech Pharmaceutical Company Inc. | Dry powder compositions for rna influenza therapeutics |
| DK1986679T3 (da) | 2006-02-22 | 2017-11-20 | Mannkind Corp | Fremgangsmåde til forbedring af mikropartiklers farmaceutiske egenskaber omfattende diketopiperazin og et aktivt indholdsstof |
| US8485180B2 (en) | 2008-06-13 | 2013-07-16 | Mannkind Corporation | Dry powder drug delivery system |
| CN103252007B (zh) | 2008-06-13 | 2016-06-22 | 曼金德公司 | 干粉吸入器和用于药物输送的系统 |
| JP5479465B2 (ja) | 2008-06-20 | 2014-04-23 | マンカインド コーポレイション | 吸入努力をリアルタイムにプロファイルする対話式機器および方法 |
| TWI614024B (zh) | 2008-08-11 | 2018-02-11 | 曼凱公司 | 超快起作用胰島素之用途 |
| EP3777878A1 (en) * | 2008-08-15 | 2021-02-17 | Acorda Therapeutics, Inc. | Compositions and methods for treatment during non-acute periods following cns neurological injury |
| US8314106B2 (en) | 2008-12-29 | 2012-11-20 | Mannkind Corporation | Substituted diketopiperazine analogs for use as drug delivery agents |
| EP2676695A3 (en) | 2009-03-11 | 2017-03-01 | MannKind Corporation | Apparatus, system and method for measuring resistance of an inhaler |
| PT2410981T (pt) | 2009-03-26 | 2017-05-25 | Pulmatrix Inc | Formulações em pó seco e métodos para tratar doenças pulmonares |
| US9018190B2 (en) | 2009-03-27 | 2015-04-28 | Adocia | Functionalized oligosaccharides |
| FR2943538B1 (fr) | 2009-03-27 | 2011-05-20 | Adocia | Formulation a action rapide d'insuline recombinante humaine |
| TWI792140B (zh) * | 2009-05-29 | 2023-02-11 | 美商沛爾醫療股份有限公司 | 用於經由呼吸道遞送二或更多種活性藥劑的組成物、方法與系統 |
| US8815258B2 (en) | 2009-05-29 | 2014-08-26 | Pearl Therapeutics, Inc. | Compositions, methods and systems for respiratory delivery of two or more active agents |
| KR101875969B1 (ko) | 2009-06-12 | 2018-07-06 | 맨카인드 코포레이션 | 한정된 비표면적을 갖는 디케토피페라진 마이크로입자 |
| GB0918450D0 (en) * | 2009-10-21 | 2009-12-09 | Innovata Ltd | Composition |
| WO2011056889A1 (en) | 2009-11-03 | 2011-05-12 | Mannkind Corporation | An apparatus and method for simulating inhalation efforts |
| RU2531455C2 (ru) | 2010-06-21 | 2014-10-20 | Маннкайнд Корпорейшн | Системы и способы доставки сухих порошковых лекарств |
| AU2011296343B2 (en) | 2010-08-30 | 2015-12-10 | Pulmatrix Operating Company, Inc. | Dry powder formulations and methods for treating pulmonary diseases |
| PT2621488T (pt) | 2010-09-29 | 2019-02-12 | Pulmatrix Operating Co Inc | Pós secos catiónicos |
| CA3086367A1 (en) | 2010-09-29 | 2012-04-05 | Pulmatrix Operating Company, Inc. | Monovalent metal cation dry powders for inhalation |
| US8485285B2 (en) * | 2011-03-22 | 2013-07-16 | Max Ferrigni | Mobile product retail system and methods thereof |
| CN105667994B (zh) | 2011-04-01 | 2018-04-06 | 曼金德公司 | 用于药物药盒的泡罩包装 |
| WO2012145603A1 (en) | 2011-04-22 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US9102313B2 (en) * | 2011-06-17 | 2015-08-11 | International Truck Intellectual Property Company, Llc | Supervisory control system for hybrid-electric powertrains |
| WO2012174472A1 (en) | 2011-06-17 | 2012-12-20 | Mannkind Corporation | High capacity diketopiperazine microparticles |
| WO2013063160A1 (en) | 2011-10-24 | 2013-05-02 | Mannkind Corporation | Methods and compositions for treating pain |
| US20130231281A1 (en) | 2011-11-02 | 2013-09-05 | Adocia | Rapid acting insulin formulation comprising an oligosaccharide |
| CN104487075A (zh) | 2012-02-29 | 2015-04-01 | 普马特里克斯公司 | 可吸入干粉剂 |
| US8988037B1 (en) * | 2012-04-06 | 2015-03-24 | The United States Of America As Represented By The Secretary Of The Navy | Solar panel storage and deployment system |
| SG11201500218VA (en) | 2012-07-12 | 2015-03-30 | Mannkind Corp | Dry powder drug delivery systems and methods |
| EP2911690A1 (en) | 2012-10-26 | 2015-09-02 | MannKind Corporation | Inhalable influenza vaccine compositions and methods |
| WO2014076423A1 (fr) | 2012-11-13 | 2014-05-22 | Adocia | Formulation à action rapide d'insuline comprenant un composé anionique substitué |
| SG11201507286QA (en) | 2013-03-15 | 2015-10-29 | Pearl Therapeutics Inc | Methods and systems for conditioning of particulate crystalline materials |
| EP2970149B1 (en) | 2013-03-15 | 2019-08-21 | MannKind Corporation | Microcrystalline diketopiperazine compositions and methods |
| AU2014248455B2 (en) | 2013-04-01 | 2018-12-06 | Pulmatrix Operating Company, Inc. | Tiotropium dry powders |
| CN105451716A (zh) | 2013-07-18 | 2016-03-30 | 曼金德公司 | 热稳定性干粉药物组合物和方法 |
| WO2015021064A1 (en) | 2013-08-05 | 2015-02-12 | Mannkind Corporation | Insufflation apparatus and methods |
| US10307464B2 (en) | 2014-03-28 | 2019-06-04 | Mannkind Corporation | Use of ultrarapid acting insulin |
| FR3020947B1 (fr) | 2014-05-14 | 2018-08-31 | Adocia | Composition aqueuse comprenant au moins une proteine et un agent solubilisant, sa preparation et ses utilisations |
| US9795678B2 (en) | 2014-05-14 | 2017-10-24 | Adocia | Fast-acting insulin composition comprising a substituted anionic compound and a polyanionic compound |
| US10561806B2 (en) | 2014-10-02 | 2020-02-18 | Mannkind Corporation | Mouthpiece cover for an inhaler |
| AR102869A1 (es) | 2014-12-16 | 2017-03-29 | Lilly Co Eli | Composiciones de insulina de rápida acción |
| DE102015004119A1 (de) * | 2015-03-31 | 2016-10-06 | Audi Ag | Kraftfahrzeug mit einem elektrischen Energiespeicher und zwei Ladeschnittstellen, Ladesystem sowie Verfahren |
| JO3749B1 (ar) | 2015-08-27 | 2021-01-31 | Lilly Co Eli | تركيبات إنسولين سريعة المفعول |
| RU2731212C2 (ru) * | 2015-09-09 | 2020-08-31 | Новартис Аг | Направленная доставка высушенных распылением композиций в легкие |
| FR3043557B1 (fr) | 2015-11-16 | 2019-05-31 | Adocia | Composition a action rapide d'insuline comprenant un citrate substitue |
| US10516189B2 (en) * | 2016-11-15 | 2019-12-24 | Ford Global Technologies, Llc | High voltage bus contactor fault detection |
| CN110662551B (zh) | 2017-06-01 | 2023-07-18 | 伊莱利利公司 | 速效胰岛素组合物 |
| AU2018392458B2 (en) * | 2017-12-21 | 2025-06-26 | Merz Pharmaceuticals, Llc | Surfactant formulations for inhalation |
| DE102021201828A1 (de) | 2021-02-26 | 2022-09-01 | Siemens Mobility GmbH | Energieversorgungsanordnung und Verfahren, insbesondere für die Energieversorgung elektrisch betriebener Fahrzeuge, beispielsweise Schienenfahrzeuge sowie elektrisch betriebenes Fahrzeug, insbesondere Schienenfahrzeug |
Family Cites Families (103)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2470296A (en) * | 1948-04-30 | 1949-05-17 | Abbott Lab | Inhalator |
| US2992645A (en) * | 1958-05-06 | 1961-07-18 | Benger Lab Ltd | Disperser for powders |
| US3957965A (en) * | 1967-08-08 | 1976-05-18 | Fisons Limited | Sodium chromoglycate inhalation medicament |
| GB1410588A (en) * | 1971-08-10 | 1975-10-22 | Fisons Ltd | Composition |
| US4069819A (en) * | 1973-04-13 | 1978-01-24 | Societa Farmaceutici S.P.A. | Inhalation device |
| US4089800A (en) * | 1975-04-04 | 1978-05-16 | Ppg Industries, Inc. | Method of preparing microcapsules |
| US4161516A (en) * | 1975-07-25 | 1979-07-17 | Fisons Limited | Composition for treating airway disease |
| US4272398A (en) * | 1978-08-17 | 1981-06-09 | The United States Of America As Represented By The Secretary Of Agriculture | Microencapsulation process |
| US4743545A (en) * | 1984-08-09 | 1988-05-10 | Torobin Leonard B | Hollow porous microspheres containing biocatalyst |
| US4391909A (en) * | 1979-03-28 | 1983-07-05 | Damon Corporation | Microcapsules containing viable tissue cells |
| US4352883A (en) * | 1979-03-28 | 1982-10-05 | Damon Corporation | Encapsulation of biological material |
| DE3274065D1 (de) * | 1981-07-08 | 1986-12-11 | Draco Ab | Powder inhalator |
| DE3268533D1 (en) * | 1981-07-24 | 1986-02-27 | Fisons Plc | Inhalation drugs, methods for their production and pharmaceutical formulations containing them |
| DE3141641A1 (de) * | 1981-10-16 | 1983-04-28 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Ultraschall-kontrastmittel und dessen herstellung |
| US4480041A (en) * | 1982-07-09 | 1984-10-30 | Collaborative Research, Inc. | Use of phosphotriester intermediates for preparation of functionalized liposomes |
| US4592436A (en) * | 1982-08-19 | 1986-06-03 | Tomei Edmardo J | Solar powered vehicle |
| US4572203A (en) * | 1983-01-27 | 1986-02-25 | Feinstein Steven B | Contact agents for ultrasonic imaging |
| US4718433A (en) * | 1983-01-27 | 1988-01-12 | Feinstein Steven B | Contrast agents for ultrasonic imaging |
| US4865789A (en) * | 1983-11-14 | 1989-09-12 | Akzo Nv | Method for making porous structures |
| ATE151286T1 (de) * | 1983-11-14 | 1997-04-15 | Columbia Lab Inc | Bioadhäsive mittel |
| US4818542A (en) * | 1983-11-14 | 1989-04-04 | The University Of Kentucky Research Foundation | Porous microspheres for drug delivery and methods for making same |
| US4679555A (en) * | 1984-08-07 | 1987-07-14 | Key Pharmaceuticals, Inc. | Method and apparatus for intrapulmonary delivery of heparin |
| JPS6150912A (ja) * | 1984-08-16 | 1986-03-13 | Shionogi & Co Ltd | リポソ−ム製剤の製造法 |
| US5340587A (en) * | 1985-05-22 | 1994-08-23 | Liposome Technology, Inc. | Liposome/bronchodilator method & System |
| ATE78158T1 (de) * | 1985-05-22 | 1992-08-15 | Liposome Technology Inc | Verfahren und system zum einatmen von liposomen. |
| EP0248051A1 (en) * | 1985-11-29 | 1987-12-09 | FISONS plc | Pharmaceutical composition including sodium cromoglycate |
| GB8601100D0 (en) * | 1986-01-17 | 1986-02-19 | Cosmas Damian Ltd | Drug delivery system |
| US4741872A (en) * | 1986-05-16 | 1988-05-03 | The University Of Kentucky Research Foundation | Preparation of biodegradable microspheres useful as carriers for macromolecules |
| EP0318492A1 (en) * | 1986-08-11 | 1989-06-07 | Innovata Biomed Limited | Pharmaceutical formulations comprising microcapsules |
| DE3637926C1 (de) * | 1986-11-05 | 1987-11-26 | Schering Ag | Ultraschall-Manometrieverfahren in einer Fluessigkeit mittels Mikroblaeschen |
| JPS63122620A (ja) * | 1986-11-12 | 1988-05-26 | Sanraku Inc | ポリ乳酸マイクロスフエア及びその製造方法 |
| US4963297A (en) * | 1987-12-22 | 1990-10-16 | The Liposome Company, Inc. | Spontaneous vesticulation of multilamellar liposomes |
| US5204113A (en) * | 1987-04-09 | 1993-04-20 | Fisons Plc | Pharmaceutical compositions containing pentamidine |
| US4861627A (en) * | 1987-05-01 | 1989-08-29 | Massachusetts Institute Of Technology | Preparation of multiwall polymeric microcapsules |
| US4857311A (en) * | 1987-07-31 | 1989-08-15 | Massachusetts Institute Of Technology | Polyanhydrides with improved hydrolytic degradation properties |
| GB8723846D0 (en) * | 1987-10-10 | 1987-11-11 | Danbiosyst Ltd | Bioadhesive microsphere drug delivery system |
| US4855144A (en) * | 1987-10-23 | 1989-08-08 | Advanced Polymer Systems | Synthetic melanin aggregates |
| JP2670680B2 (ja) * | 1988-02-24 | 1997-10-29 | 株式会社ビーエムジー | 生理活性物質含有ポリ乳酸系微小球およびその製造法 |
| US4917119A (en) * | 1988-11-30 | 1990-04-17 | R. J. Reynolds Tobacco Company | Drug delivery article |
| IT1228459B (it) * | 1989-02-23 | 1991-06-19 | Phidea S R L | Inalatore con svuotamento regolare e completo della capsula. |
| EP0471036B2 (en) * | 1989-05-04 | 2004-06-23 | Southern Research Institute | Encapsulation process |
| US5176132A (en) * | 1989-05-31 | 1993-01-05 | Fisons Plc | Medicament inhalation device and formulation |
| US5174988A (en) * | 1989-07-27 | 1992-12-29 | Scientific Development & Research, Inc. | Phospholipid delivery system |
| IT1237118B (it) * | 1989-10-27 | 1993-05-18 | Miat Spa | Inalatore multidose per farmaci in polvere. |
| US5707644A (en) * | 1989-11-04 | 1998-01-13 | Danbiosyst Uk Limited | Small particle compositions for intranasal drug delivery |
| US5123414A (en) * | 1989-12-22 | 1992-06-23 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
| US5334381A (en) * | 1989-12-22 | 1994-08-02 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
| US5352435A (en) * | 1989-12-22 | 1994-10-04 | Unger Evan C | Ionophore containing liposomes for ultrasound imaging |
| SE9002017D0 (sv) * | 1990-06-06 | 1990-06-06 | Kabivitrum Ab | Process for manufacture of matrices |
| US5614216A (en) * | 1990-10-17 | 1997-03-25 | The Liposome Company, Inc. | Synthetic lung surfactant |
| US5145684A (en) * | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| GB9107628D0 (en) * | 1991-04-10 | 1991-05-29 | Moonbrook Limited | Preparation of diagnostic agents |
| US5874063A (en) * | 1991-04-11 | 1999-02-23 | Astra Aktiebolag | Pharmaceutical formulation |
| SE9302777D0 (sv) * | 1993-08-27 | 1993-08-27 | Astra Ab | Process for conditioning substances |
| US5327883A (en) * | 1991-05-20 | 1994-07-12 | Dura Pharmaceuticals, Inc. | Apparatus for aerosolizing powdered medicine and process and using |
| AU659645B2 (en) * | 1991-06-26 | 1995-05-25 | Inhale Therapeutic Systems | Storage of materials |
| KR100291620B1 (ko) * | 1992-09-29 | 2001-10-24 | 추후제출 | 부갑상선호르몬의활성단편의폐를통한전달방법 |
| SE9203743D0 (sv) * | 1992-12-11 | 1992-12-11 | Astra Ab | Efficient use |
| US5698721A (en) * | 1992-12-17 | 1997-12-16 | Megabios Corporation | Catonic amphiphiles |
| US5603945A (en) * | 1993-02-19 | 1997-02-18 | Takeda Chemical Industries, Ltd. | Therapeutic/prophylactic agents and method of treating for urinary calculosis in pets |
| SE9301220D0 (sv) * | 1993-04-14 | 1993-04-14 | Kabi Pharmacia Ab | Manufacturing matrices |
| TW402506B (en) * | 1993-06-24 | 2000-08-21 | Astra Ab | Therapeutic preparation for inhalation |
| US5506203C1 (en) * | 1993-06-24 | 2001-02-06 | Astra Ab | Systemic administration of a therapeutic preparation |
| GB9313650D0 (en) * | 1993-07-01 | 1993-08-18 | Glaxo Group Ltd | Method and apparatus for the formation of particles |
| ES2166786T3 (es) * | 1993-10-01 | 2002-05-01 | Astrazeneca Ab | Procedimiento i. |
| GB9322014D0 (en) * | 1993-10-26 | 1993-12-15 | Co Ordinated Drug Dev | Improvements in and relating to carrier particles for use in dry powder inhalers |
| ATE264096T1 (de) * | 1994-03-07 | 2004-04-15 | Nektar Therapeutics | Verfahren und mittel zur verabreichung von insulin über die lunge |
| US6051256A (en) * | 1994-03-07 | 2000-04-18 | Inhale Therapeutic Systems | Dispersible macromolecule compositions and methods for their preparation and use |
| WO1995031479A1 (en) * | 1994-05-18 | 1995-11-23 | Inhale Therapeutic Systems, Inc. | Methods and compositions for the dry powder formulation of interferons |
| GB9413202D0 (en) * | 1994-06-30 | 1994-08-24 | Univ Bradford | Method and apparatus for the formation of particles |
| GB9413605D0 (en) * | 1994-07-06 | 1994-08-24 | American Colloid Co | Method of increasing the size and absorption under load of super-absorbent fine particles by impregnation with an aqueous acrylic monomer solution |
| US5486569A (en) * | 1994-09-28 | 1996-01-23 | American Colloid Company | Method of increasing the size and/or absorption under load of superabsorbent polymers by surface cross-linking and subsequent agglomeration of undersized particcles |
| US5885613A (en) * | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| US5648101A (en) * | 1994-11-14 | 1997-07-15 | Tawashi; Rashad | Drug delivery of nitric oxide |
| SA95160463B1 (ar) * | 1994-12-22 | 2005-10-04 | استرا أكتيبولاج | مساحيق للاستنشاق |
| US5612053A (en) * | 1995-04-07 | 1997-03-18 | Edward Mendell Co., Inc. | Controlled release insufflation carrier for medicaments |
| US6258341B1 (en) * | 1995-04-14 | 2001-07-10 | Inhale Therapeutic Systems, Inc. | Stable glassy state powder formulations |
| US5780014A (en) * | 1995-04-14 | 1998-07-14 | Inhale Therapeutic Systems | Method and apparatus for pulmonary administration of dry powder alpha 1-antitrypsin |
| ES2237767T3 (es) * | 1995-04-14 | 2005-08-01 | Nektar Therapeutics | Composiciones farmaceuticas en polvo que tienen una dispersabilidad mejorada. |
| US6019968A (en) * | 1995-04-14 | 2000-02-01 | Inhale Therapeutic Systems, Inc. | Dispersible antibody compositions and methods for their preparation and use |
| US5637980A (en) * | 1995-05-08 | 1997-06-10 | Wu; Jimmy | Battery charging/discharging switching control protective circuit |
| US5654007A (en) * | 1995-06-07 | 1997-08-05 | Inhale Therapeutic Systems | Methods and system for processing dispersible fine powders |
| US20020052310A1 (en) * | 1997-09-15 | 2002-05-02 | Massachusetts Institute Of Technology The Penn State Research Foundation | Particles for inhalation having sustained release properties |
| USRE37053E1 (en) * | 1996-05-24 | 2001-02-13 | Massachusetts Institute Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
| US5855913A (en) * | 1997-01-16 | 1999-01-05 | Massachusetts Instite Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
| US5874064A (en) * | 1996-05-24 | 1999-02-23 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
| US6103270A (en) * | 1996-06-07 | 2000-08-15 | Inhale Therapeutic Systems | Methods and system for processing dispersible fine powders |
| US6096291A (en) * | 1996-12-27 | 2000-08-01 | Biovector Therapeutics, S.A. | Mucosal administration of substances to mammals |
| WO1998029098A1 (en) * | 1996-12-31 | 1998-07-09 | Inhale Therapeutic Systems, Inc. | Processes for spray drying aqueous suspensions of hydrophobic drugs with hydrophilic excipients and compositions prepared by such processes |
| SE9700133D0 (sv) * | 1997-01-20 | 1997-01-20 | Astra Ab | New formulation |
| WO1998045654A1 (en) * | 1997-04-10 | 1998-10-15 | Nucon Systems, Inc. | Process and apparatus for the preparation of thick-walled ceramic products |
| US6433040B1 (en) * | 1997-09-29 | 2002-08-13 | Inhale Therapeutic Systems, Inc. | Stabilized bioactive preparations and methods of use |
| US6187330B1 (en) * | 1998-01-30 | 2001-02-13 | Scios Inc. | Controlled release delivery of peptide or protein |
| BR9909492A (pt) * | 1998-04-08 | 2000-12-12 | Lilly Co Eli | Liberação pulmonar e nasal de raloxifeno |
| US5986429A (en) * | 1998-06-29 | 1999-11-16 | Mula, Jr.; John | Battery charging system for electric vehicles |
| US6586668B2 (en) * | 1999-02-05 | 2003-07-01 | Powerlight Corporation | Electric vehicle with photovoltaic roof assembly |
| DE19937221C1 (de) * | 1999-08-06 | 2000-09-07 | Webasto Dachsysteme Gmbh | Solar-Fahrzeugdach |
| US6227601B1 (en) * | 2000-03-20 | 2001-05-08 | Lafrance Joseph E. | Motor driven sunshield |
| US6735645B1 (en) * | 2001-09-04 | 2004-05-11 | Lsi Logic Corporation | System and method to eliminate race conditions in input/output operations for high bandwidth architectures |
| US6617822B1 (en) * | 2001-09-12 | 2003-09-09 | Bellsouth Intellectual Property Corporation | System and method to maintain charge of vehicle battery using light energy |
| US20040201244A1 (en) * | 2002-12-31 | 2004-10-14 | Leon Neuer | Automobile sunshade |
| US7140662B1 (en) * | 2003-10-06 | 2006-11-28 | Wilkinson Kari L | Retractable sunshade |
| US7718923B1 (en) * | 2007-02-09 | 2010-05-18 | Hansen Scott P | Defrosting windshield sunshade panel |
-
2001
- 2001-06-22 US US09/888,126 patent/US20020141946A1/en not_active Abandoned
-
2002
- 2002-06-24 IL IL15898702A patent/IL158987A0/xx unknown
- 2002-06-24 JP JP2003506648A patent/JP4067047B2/ja not_active Expired - Fee Related
- 2002-06-24 PL PL02367399A patent/PL367399A1/xx unknown
- 2002-06-24 NZ NZ530123A patent/NZ530123A/en unknown
- 2002-06-24 MX MXPA03011861A patent/MXPA03011861A/es not_active Application Discontinuation
- 2002-06-24 EP EP02752100A patent/EP1404299A2/en not_active Withdrawn
- 2002-06-24 CA CA002449439A patent/CA2449439A1/en not_active Abandoned
- 2002-06-24 CN CNA028125665A patent/CN1518441A/zh active Pending
- 2002-06-24 WO PCT/US2002/020280 patent/WO2003000202A2/en not_active Ceased
-
2007
- 2007-09-24 US US11/860,357 patent/US20080227690A1/en not_active Abandoned
-
2009
- 2009-09-01 US US12/552,238 patent/US20100026235A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1404299A2 (en) | 2004-04-07 |
| MXPA03011861A (es) | 2004-03-26 |
| WO2003000202A3 (en) | 2003-08-14 |
| NZ530123A (en) | 2007-01-26 |
| CN1518441A (zh) | 2004-08-04 |
| US20100026235A1 (en) | 2010-02-04 |
| WO2003000202A2 (en) | 2003-01-03 |
| PL367399A1 (en) | 2005-02-21 |
| JP2005500309A (ja) | 2005-01-06 |
| US20020141946A1 (en) | 2002-10-03 |
| JP4067047B2 (ja) | 2008-03-26 |
| IL158987A0 (en) | 2004-05-12 |
| US20080227690A1 (en) | 2008-09-18 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |