JP4156665B2 - 薬剤を充填した微粒子を製造するためのシステムと方法 - Google Patents

薬剤を充填した微粒子を製造するためのシステムと方法 Download PDF

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Publication number
JP4156665B2
JP4156665B2 JP50216797A JP50216797A JP4156665B2 JP 4156665 B2 JP4156665 B2 JP 4156665B2 JP 50216797 A JP50216797 A JP 50216797A JP 50216797 A JP50216797 A JP 50216797A JP 4156665 B2 JP4156665 B2 JP 4156665B2
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Prior art keywords
alginate
icam
drug
mixing chamber
emulsifier
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Expired - Lifetime
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JP50216797A
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English (en)
Japanese (ja)
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JPH11507382A (ja
JPH11507382A5 (enExample
Inventor
ボンバーガー，デビッド，シー．
キャッツ，ポール，ジー．
スメドレー，マーク，アイ．
ステアーンズ，ポール，シー．
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エス アール アイ インターナショナル
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Publication of JPH11507382A5 publication Critical patent/JPH11507382A5/ja
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • A—HUMAN NECESSITIES
    • 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
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/1774—Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
    • 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
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Cell Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
JP50216797A 1995-06-07 1996-06-06 薬剤を充填した微粒子を製造するためのシステムと方法 Expired - Lifetime JP4156665B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/480,624 1995-06-07
US08/480,624 US5879712A (en) 1995-06-07 1995-06-07 Method for producing drug-loaded microparticles and an ICAM-1 dosage form so produced
PCT/US1996/010031 WO1996040069A1 (en) 1995-06-07 1996-06-06 System and method for producing drug-loaded microparticles

Publications (3)

Publication Number Publication Date
JPH11507382A JPH11507382A (ja) 1999-06-29
JPH11507382A5 JPH11507382A5 (enExample) 2004-07-29
JP4156665B2 true JP4156665B2 (ja) 2008-09-24

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ID=23908687

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JP50216797A Expired - Lifetime JP4156665B2 (ja) 1995-06-07 1996-06-06 薬剤を充填した微粒子を製造するためのシステムと方法

Country Status (8)

Country Link
US (3) US5879712A (enExample)
EP (1) EP0833614B1 (enExample)
JP (1) JP4156665B2 (enExample)
AT (1) ATE353631T1 (enExample)
CA (1) CA2224074C (enExample)
DE (1) DE69636904T2 (enExample)
ES (1) ES2281084T3 (enExample)
WO (1) WO1996040069A1 (enExample)

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6514936B1 (en) 1988-09-01 2003-02-04 Bayer Corporation Antiviral methods using human rhinovirus receptor (ICAM-1)
DE68929096T2 (de) 1988-09-01 2000-05-11 Bayer Corp., Pittsburgh Menschliches Rhinovirusrezeptorprotein, das die Virusinfektionsanfälligkeit hemmt
US6235313B1 (en) 1992-04-24 2001-05-22 Brown University Research Foundation Bioadhesive microspheres and their use as drug delivery and imaging systems
US5879712A (en) * 1995-06-07 1999-03-09 Sri International Method for producing drug-loaded microparticles and an ICAM-1 dosage form so produced
ATE242001T1 (de) 1996-03-06 2003-06-15 Boehringer Ingelheim Pharma Pulverförmiges arzneimittel enthaltend interzelluläres adhäsionsmolekül
US20020182258A1 (en) * 1997-01-22 2002-12-05 Zycos Inc., A Delaware Corporation Microparticles for delivery of nucleic acid
IT1291559B1 (it) * 1997-04-14 1999-01-11 Univ Degli Studi Milano Uso di microparticelle su cui sono stati adsorbiti una proteina ed un anticorpo per preparare una composizione farmaceutica somministrabile
US6391452B1 (en) 1997-07-18 2002-05-21 Bayer Corporation Compositions for nasal drug delivery, methods of making same, and methods of removing residual solvent from pharmaceutical preparations
WO1999022768A1 (en) * 1997-10-31 1999-05-14 Monsanto Company Controlled release compositions comprising gellan gum gels
US6395298B1 (en) * 1997-10-31 2002-05-28 Pharmacia Corporation Gellan gum tablet coating
DE69817009T2 (de) * 1997-11-10 2004-06-09 Quest International B.V. Verkapseltes aktives material in einer alginatmatrix
US6485747B1 (en) * 1998-10-30 2002-11-26 Monsanto Company Coated active tablet(s)
US6248321B1 (en) * 1999-01-14 2001-06-19 Her Majesty The Queen In Right Of Canada, As Represented By The Minister Of Natural Resources, Canadian Forestry Service Encapsulation of microparticles in teardrop shaped polymer capsules of cellular size
DE19904785A1 (de) * 1999-02-05 2000-08-10 Ulrich Zimmermann Verfahren zur Herstellung von stabilem Alginatmaterial
US6927223B1 (en) 2000-05-26 2005-08-09 Washington State University Research Foundation Use of serotonin agents for adjunct therapy in the treatment of cancer
CN1458846A (zh) * 2000-09-08 2003-11-26 格莱风治疗公司 促红细胞生成性合成蛋白
US7118737B2 (en) * 2000-09-08 2006-10-10 Amylin Pharmaceuticals, Inc. Polymer-modified synthetic proteins
US7008650B2 (en) * 2001-08-09 2006-03-07 Lam Paul Y S Compositions for the treatment of acquired immunodeficiency disease
EP2075256A2 (en) 2002-01-14 2009-07-01 William Herman Multispecific binding molecules
WO2004000280A1 (en) * 2002-04-29 2003-12-31 Shire Laboraties, Inc. Pharmaceutical formulations with improved bioavailability
US20030206957A1 (en) * 2002-05-06 2003-11-06 Scherr George H. Orally administered medicament delivery systems
GB2399084B (en) * 2002-07-30 2007-01-31 Univ Liverpool Porous beads and method of production thereof
KR20050083774A (ko) 2002-10-16 2005-08-26 유로-셀티크 소시에떼 아노뉨 세포-연관된 ｃａ 125/ｏ772ｐ에 결합하는 항체들 및그것의 용도의 방법들
JP4463109B2 (ja) * 2002-11-07 2010-05-12 アドバンスド バイオニュートリション コーポレーション 栄養補助食品および水生動物の給餌方法
US20050053655A1 (en) * 2003-09-05 2005-03-10 Pharmaceutical Industry Technology And Development Center Rapid disintegrating tablets (RDTs) for pharmaceutical use and method for preparing the same
US7410978B2 (en) * 2003-11-04 2008-08-12 Supernus Pharmaceuticals, Inc. Once daily dosage forms of trospium
AU2004289222B2 (en) 2003-11-04 2010-01-21 Supernus Pharmaceuticals Inc. Compositions of quaternary ammonium containing bioavailability enhancers
US20050260258A1 (en) * 2003-12-18 2005-11-24 The Texas A&M University System Use of vitelline protein B as a microencapsulating additive
US20060045865A1 (en) * 2004-08-27 2006-03-02 Spherics, Inc. Controlled regional oral delivery
WO2006026504A2 (en) * 2004-08-27 2006-03-09 Spherics, Inc. Mucoadhesive oral formulations of high permeability, high solubility drugs
US7115561B2 (en) * 2004-09-22 2006-10-03 Patterson James A Medicament composition and method of administration
US9492400B2 (en) * 2004-11-04 2016-11-15 Massachusetts Institute Of Technology Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals
AR048220A1 (es) * 2005-01-28 2006-04-12 Lkm S A Lab Arreglo de dispositivos utilizables en la elaboracion de microcapsulas para la liberacion controlada de peptidos y procedimiento de elaboracion de dichas opcionalmente sustituido
WO2007025244A2 (en) 2005-08-25 2007-03-01 Houle Philip R Treatment systems for delivery of sensitizer solutions
US9267937B2 (en) 2005-12-15 2016-02-23 Massachusetts Institute Of Technology System for screening particles
WO2008105773A2 (en) * 2006-03-31 2008-09-04 Massachusetts Institute Of Technology System for targeted delivery of therapeutic agents
US20110052697A1 (en) * 2006-05-17 2011-03-03 Gwangju Institute Of Science & Technology Aptamer-Directed Drug Delivery
WO2007150030A2 (en) * 2006-06-23 2007-12-27 Massachusetts Institute Of Technology Microfluidic synthesis of organic nanoparticles
US20100144845A1 (en) * 2006-08-04 2010-06-10 Massachusetts Institute Of Technology Oligonucleotide systems for targeted intracellular delivery
WO2008031780A2 (de) * 2006-09-13 2008-03-20 Basf Se Verfahren zur herstellung feinteiliger dispersionen
US7731604B2 (en) * 2006-10-31 2010-06-08 Taylor Made Golf Company, Inc. Golf club iron head
WO2008147456A2 (en) * 2006-11-20 2008-12-04 Massachusetts Institute Of Technology Drug delivery systems using fc fragments
US9217129B2 (en) 2007-02-09 2015-12-22 Massachusetts Institute Of Technology Oscillating cell culture bioreactor
WO2008124639A2 (en) * 2007-04-04 2008-10-16 Massachusetts Institute Of Technology Poly (amino acid) targeting moieties
BRPI0817664A2 (pt) 2007-10-12 2015-03-24 Massachusetts Inst Technology Nanopartículas, método para preparar nanopartículas e método para tratar terapeuticamente ou profilaticamente um indivíduo
US20100015240A1 (en) * 2008-07-16 2010-01-21 Danielle Biggs Process for preparing microparticles containing bioactive peptides
US8277812B2 (en) 2008-10-12 2012-10-02 Massachusetts Institute Of Technology Immunonanotherapeutics that provide IgG humoral response without T-cell antigen
US8591905B2 (en) 2008-10-12 2013-11-26 The Brigham And Women's Hospital, Inc. Nicotine immunonanotherapeutics
PT2506859T (pt) * 2009-12-04 2016-08-12 Magle Ab Microesferas de amido hidrolisado com ligandos endógenos carregados
WO2015071366A1 (en) * 2013-11-13 2015-05-21 Tillotts Pharma Ag Multi-particulate drug delivery system
DE112016001911A5 (de) * 2015-05-21 2018-01-11 Arnold Lösler Matrixmembranschicht auf Alginatbasis
CN117942405A (zh) 2016-02-25 2024-04-30 应用生物实验室公司 保护空气传播的病原体和刺激物的组合物和方法
US12447166B2 (en) 2016-02-25 2025-10-21 Applied Biological Laboratories, Inc. Compositions and methods for protecting against airborne pathogens and irritants

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2042888B (en) * 1979-03-05 1983-09-28 Teijin Ltd Preparation for administration to the mucosa of the oral or nasal cavity
US4278206A (en) * 1979-04-13 1981-07-14 Ae Development Corporation Non-pressurized dispensing system
JPS6034925B2 (ja) * 1979-07-31 1985-08-12 帝人株式会社 持続性鼻腔用製剤およびその製造法
US4389330A (en) 1980-10-06 1983-06-21 Stolle Research And Development Corporation Microencapsulation process
US4350840A (en) * 1981-03-20 1982-09-21 Ideal Industries, Inc. Cord grip
JPS6032714A (ja) * 1983-08-01 1985-02-19 Teijin Ltd 鼻腔粘膜に適用するための安定化された粉末状薬学的組成物
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
JPS61138529A (ja) * 1984-12-10 1986-06-26 Idemitsu Petrochem Co Ltd サイズ用乳化液の製造方法
EP0188040B1 (en) * 1985-01-11 1991-08-14 Abbott Laboratories Limited Slow release solid preparation
GB8501015D0 (en) * 1985-01-16 1985-02-20 Riker Laboratories Inc Drug
US5059587A (en) * 1987-08-03 1991-10-22 Toyo Jozo Company, Ltd. Physiologically active peptide composition for nasal administration
GB8723846D0 (en) * 1987-10-10 1987-11-11 Danbiosyst Ltd Bioadhesive microsphere drug delivery system
EP0314863B1 (en) * 1987-11-02 1994-12-07 Baylor College Of Medicine Use of ICAM-1 or its functional derivatives for the treatment of non-specific inflammation
US5079005A (en) * 1988-06-17 1992-01-07 Gupta Kashmiri L Time release protein
DE68929096T2 (de) 1988-09-01 2000-05-11 Bayer Corp., Pittsburgh Menschliches Rhinovirusrezeptorprotein, das die Virusinfektionsanfälligkeit hemmt
EP0471036B2 (en) * 1989-05-04 2004-06-23 Southern Research Institute Encapsulation process
GB2237510B (en) * 1989-11-04 1993-09-15 Danbiosyst Uk Small particle drug compositions for nasal administration
US5271961A (en) * 1989-11-06 1993-12-21 Alkermes Controlled Therapeutics, Inc. Method for producing protein microspheres
FR2655732B1 (fr) 1989-12-11 1992-02-07 Snecma Procede et dispositif de controle du collage d'un nida sur un support.
EP0468257B1 (en) 1990-07-20 1999-09-01 Bayer Corporation Multimeric form of human rhinovirus receptor protein
US5292499A (en) * 1990-09-11 1994-03-08 University Of Wales College Of Cardiff Method of preparing medical aerosol formulations including drug dissolved in reverse micelles
WO1993006842A1 (en) * 1991-10-02 1993-04-15 Boehringer Ingelheim Pharmaceuticals, Inc. Use of intercellular adhesion molecules, and their binding ligands in the treatment of asthma
FR2686250A1 (fr) * 1992-01-16 1993-07-23 Coletica Compositions injectables contenant en suspension des microcapsules a base de collagene, leur utilisation biomedicale et des compositions pharmaceutiques.
CA2167081A1 (en) * 1993-07-12 1995-01-26 Alexander K. Andrianov Hydrogel microencapsulated vaccines
JP3285427B2 (ja) * 1993-08-04 2002-05-27 冷化工業株式会社 エマルション製造装置及び方法
EP2275089A1 (en) * 1993-11-19 2011-01-19 Alkermes Controlled Therapeutics, Inc. Preparation of biodegradable microparticles containing a biologically active agent
GB9414966D0 (en) * 1994-07-26 1994-09-14 Danbiosyst Uk Pharmaceutical compositions for the nasal administration of antiviral agents
US5840254A (en) * 1995-06-02 1998-11-24 Cdc Technologies, Inc. Apparatus for mixing fluids for analysis
US5879712A (en) * 1995-06-07 1999-03-09 Sri International Method for producing drug-loaded microparticles and an ICAM-1 dosage form so produced

Also Published As

Publication number Publication date
EP0833614A4 (en) 2001-07-11
US20030091649A1 (en) 2003-05-15
US5879712A (en) 1999-03-09
JPH11507382A (ja) 1999-06-29
US7087245B2 (en) 2006-08-08
CA2224074A1 (en) 1996-12-19
ATE353631T1 (de) 2007-03-15
EP0833614A1 (en) 1998-04-08
WO1996040069A1 (en) 1996-12-19
DE69636904D1 (de) 2007-03-29
US6375985B1 (en) 2002-04-23
DE69636904T2 (de) 2007-11-15
EP0833614B1 (en) 2007-02-14
CA2224074C (en) 2009-09-08
ES2281084T3 (es) 2007-09-16

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