SK11142002A3 - Liečivo na podávanie interleukínu-2 a stabilizovaný lyofilizovaný alebo sprejovo sušený farmaceutický prostriedok s obsahom interleukínu-2 - Google Patents

Liečivo na podávanie interleukínu-2 a stabilizovaný lyofilizovaný alebo sprejovo sušený farmaceutický prostriedok s obsahom interleukínu-2 Download PDF

Info

Publication number: SK11142002A3
Authority: SK; Slovakia
Prior art keywords: composition; dry powder; pulmonary inhalation; surfactant; polysorbate
Prior art date: 1999-12-30

Application number

SK1114-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Bao-Lu Chen

Maninder Hora

Original Assignee

Chiron Corporation

Priority date (The priority date 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 date listed.)

1999-12-30

Filing date

2000-12-27

Publication date

2004-09-08

2000-12-27 Application filed by Chiron Corporation filed Critical Chiron Corporation

2004-09-08 Publication of SK11142002A3 publication Critical patent/SK11142002A3/sk

Links

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- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- 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
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
- 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
- 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
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions

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Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
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Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Otolaryngology (AREA)
General Chemical & Material Sciences (AREA)
Pulmonology (AREA)
Immunology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Oil, Petroleum & Natural Gas (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Medicinal Preparation (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK1114-2002A 1999-12-30 2000-12-27 Liečivo na podávanie interleukínu-2 a stabilizovaný lyofilizovaný alebo sprejovo sušený farmaceutický prostriedok s obsahom interleukínu-2 SK11142002A3 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US17392299P	1999-12-30	1999-12-30
US72481000A	2000-11-28	2000-11-28
PCT/US2000/035452 WO2001049274A2 (fr)	1999-12-30	2000-12-27	Procedes d'administration pulmonaire d'interleukine-2

Publications (1)

Publication Number	Publication Date
SK11142002A3 true SK11142002A3 (sk)	2004-09-08

Family

ID=26869690

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1114-2002A SK11142002A3 (sk)	1999-12-30	2000-12-27	Liečivo na podávanie interleukínu-2 a stabilizovaný lyofilizovaný alebo sprejovo sušený farmaceutický prostriedok s obsahom interleukínu-2

Country Status (15)

Country	Link
US (2)	US20030198602A1 (fr)
EP (1)	EP1244432A2 (fr)
JP (1)	JP2003519175A (fr)
CN (1)	CN100333790C (fr)
AU (1)	AU783795B2 (fr)
BR (1)	BR0016879A (fr)
CA (1)	CA2395887A1 (fr)
CZ (1)	CZ20022265A3 (fr)
HU (1)	HUP0204136A3 (fr)
IL (2)	IL150461A0 (fr)
NO (1)	NO20023123L (fr)
NZ (1)	NZ520379A (fr)
PL (1)	PL356641A1 (fr)
SK (1)	SK11142002A3 (fr)
WO (1)	WO2001049274A2 (fr)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20030113271A1 (en) *	1997-01-29	2003-06-19	University Technology Corporation	Formulations for pulmonary delivery
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
JP2003524646A (ja) *	2000-01-25	2003-08-19	エアロファームテクノロジーインコーポレイテッド	医薬エアゾール製剤
JP4147234B2 (ja)	2004-09-27	2008-09-10	キヤノン株式会社	吐出用液体、吐出方法、カートリッジ及び吐出装置
AU2002335046A1 (en) *	2001-10-19	2003-05-06	Inhale Therapeutic Systems, Inc.	The use of proton sequestering agents in drug formulations
EP1494732B1 (fr)	2002-03-20	2008-01-30	MannKind Corporation	Appareil d'inhalation
JP5057648B2 (ja) *	2002-09-26	2012-10-24	塩野義製薬株式会社	安定化されたタンパク組成物
EP1589949B1 (fr) *	2003-01-08	2008-08-13	Novartis Vaccines and Diagnostics, Inc.	Compositions lyophilisees stabilisees renfermant un inhibiteur de la voie du facteur tissulaire ou des variantes d'un inhibiteur de la voie du facteur tissulaire
EP1803445A3 (fr) *	2003-01-08	2007-11-21	Novartis Vaccines and Diagnostics, Inc.	Compositions lyophilisées stabilisées renfermant un inhibiteur de la voie du facteur tissulaire ou des variantes d'un inhibiteur de la voie du facteur tissulaire
DK1786784T3 (da)	2004-08-20	2011-02-14	Mannkind Corp	Katalyse af diketopiperazinsyntese
CN104436170B (zh)	2004-08-23	2018-02-23	曼金德公司	用于药物输送的二酮哌嗪盐
JP4147235B2 (ja)	2004-09-27	2008-09-10	キヤノン株式会社	吐出用液体、吐出方法、液滴化方法、液体吐出カートリッジ及び吐出装置
WO2006130943A1 (fr) *	2005-06-10	2006-12-14	The Governors Of The University Of Alberta	Formule de poudre sechee inhalable comprenant des nanoparticules chargees d'un medicament
AU2006290227B2 (en)	2005-09-14	2012-08-02	Mannkind Corporation	Method of drug formulation based on increasing the affinity of crystalline microparticle surfaces for active agents
TWI299993B (en)	2005-12-15	2008-08-21	Dev Center Biotechnology	Aqueous inhalation pharmaceutical composition
KR20080096809A (ko)	2006-02-22	2008-11-03	맨카인드 코포레이션	디케토피페라진 및 활성제를 포함하는 마이크로입자의 약학특성의 개선 방법
CN101125199B (zh) *	2006-08-15	2010-07-21	北京四环生物制药有限公司	白介素2作为制备治疗鼻炎药物的应用
US8485180B2 (en)	2008-06-13	2013-07-16	Mannkind Corporation	Dry powder drug delivery system
SG10201507036TA (en)	2008-06-13	2015-10-29	Mannkind Corp	A dry powder inhaler and system for drug delivery
EP2609954B1 (fr)	2008-06-20	2021-12-29	MannKind Corporation	Appareil interactif pour l'établissement en temps réel d'un profil des efforts d'inhalation
TWI614024B (zh)	2008-08-11	2018-02-11	曼凱公司	超快起作用胰島素之用途
US8314106B2 (en)	2008-12-29	2012-11-20	Mannkind Corporation	Substituted diketopiperazine analogs for use as drug delivery agents
MX2011009512A (es)	2009-03-11	2011-11-29	Mannkind Corp	Aparato, sistema y metodo para medir la resistencia de un inhalador.
MY157166A (en)	2009-06-12	2016-05-13	Mankind Corp	Diketopiperazine microparticles with defined specific surface areas
CA2778698A1 (fr)	2009-11-03	2011-05-12	Mannkind Corporation	Appareil et methode de simulation d'efforts d'inhalation
IL223742A (en)	2010-06-21	2016-06-30	Mannkind Corp	A dry powder inhaler and preparation for it
EP2694402B1 (fr)	2011-04-01	2017-03-22	MannKind Corporation	Emballage coque pour cartouches pharmaceutiques
WO2012174472A1 (fr)	2011-06-17	2012-12-20	Mannkind Corporation	Microparticules de dicétopipérazine de capacité élevée
EP2550863A1 (fr) *	2011-07-27	2013-01-30	Bayer Intellectual Property GmbH	Particules contenant une matière active à base de polyacrylate
HK1200318A1 (en)	2011-10-24	2015-08-07	曼金德公司	Methods and compositions for treating pain
EP2872205B1 (fr)	2012-07-12	2017-02-08	MannKind Corporation	Systèmes de libération de médicament en poudre sèche
US10159644B2 (en)	2012-10-26	2018-12-25	Mannkind Corporation	Inhalable vaccine compositions and methods
WO2014144895A1 (fr)	2013-03-15	2014-09-18	Mannkind Corporation	Compositions de dicétopipérazine microcristallines et procédés
KR102465025B1 (ko)	2013-07-18	2022-11-09	맨카인드 코포레이션	열-안정성 건조 분말 약제학적 조성물 및 방법
EP3030294B1 (fr)	2013-08-05	2020-10-07	MannKind Corporation	Appareil d'insufflation
US10307464B2 (en)	2014-03-28	2019-06-04	Mannkind Corporation	Use of ultrarapid acting insulin
US10561806B2 (en)	2014-10-02	2020-02-18	Mannkind Corporation	Mouthpiece cover for an inhaler
US11224594B2 (en)	2015-09-16	2022-01-18	Philip Morris Products S.A.	Nicotine formulations and methods of making and using the same
US9585835B1 (en) *	2015-09-16	2017-03-07	Sansa Corporation (Barbados) Inc.	Inhalable nicotine formulations and methods of making and using the same
CA3001429C (fr) *	2015-10-22	2023-07-11	Iltoo Pharma	Compositions pharmaceutiques d'il-2
EP3478264B1 (fr) *	2016-06-30	2025-11-19	Philip Morris Products S.A.	Particules et compositions de nicotine
WO2018081213A1 (fr) *	2016-10-25	2018-05-03	Marquette University	Supports et formulations pulvérulentes pour dents avulsées et tissus explantés comprenant des fibroblastes
CA3172871A1 (fr) *	2020-05-11	2021-11-18	Francisca O. GBORMITTAH	Compositions de polypeptides de fusion d'il-2 et leurs procedes de fabrication et d'utilisation
US12024559B2 (en)	2020-10-23	2024-07-02	Asher Biotherapeutics, Inc.	Fusions with CD8 antigen binding molecules for modulating immune cell function
WO2022100686A1 (fr) *	2020-11-13	2022-05-19	江苏恒瑞医药股份有限公司	Composition pharmaceutique comprenant un variant ou un dérivé d'il-2 humaine et son utilisation
CN121466042A (zh) *	2026-01-09	2026-02-06	苏州市立医院	一种吸入用药物组合物及其用途

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4604377A (en) *	1984-03-28	1986-08-05	Cetus Corporation	Pharmaceutical compositions of microbially produced interleukin-2
US5037644A (en) *	1986-10-27	1991-08-06	Cetus Corporation	Pharmaceutical compositions of recombinant interleukin-2 and formulation processes
US4927850A (en) *	1988-04-08	1990-05-22	Bayless Robert K	Antioxidant compositions and methods for ameliorating inflammatory symptoms of respiratory disease
US5078997A (en) *	1988-07-13	1992-01-07	Cetus Corporation	Pharmaceutical composition for interleukin-2 containing physiologically compatible stabilizers
DK0462305T3 (da) *	1990-06-21	1995-04-24	Huland Edith	Anvendelse af cytokinholdige aerosoler såvel som cytokholdige aerosoler i sig selv
US5780012A (en) *	1990-06-21	1998-07-14	Huland; Edith	Method for reducing lung afflictions by inhalation of cytokine solutions
NZ241954A (en) *	1991-03-15	1994-01-26	Amgen Inc	Compositions of g-csf for pulmonary administration.
US5354934A (en) *	1993-02-04	1994-10-11	Amgen Inc.	Pulmonary administration of erythropoietin
FI960253A7 (fi) *	1993-07-19	1996-03-18	Amgen Inc	Aerosolisoitujen proteiinien stabilointi
ES2218543T3 (es) *	1994-03-07	2004-11-16	Nektar Therapeutics	Procedimiento y preparacion para la administracion de insulina por via pulmonar.
US5985309A (en) *	1996-05-24	1999-11-16	Massachusetts Institute Of Technology	Preparation of particles for inhalation
US5874064A (en) *	1996-05-24	1999-02-23	Massachusetts Institute Of Technology	Aerodynamically light particles for pulmonary drug delivery
US5855913A (en) *	1997-01-16	1999-01-05	Massachusetts Instite Of Technology	Particles incorporating surfactants for pulmonary drug delivery
CN1245216C (zh) *	1999-10-04	2006-03-15	希龙公司	稳定化的含多肽的液体药物组合物

2000
- 2000-12-27 EP EP00989539A patent/EP1244432A2/fr not_active Withdrawn
- 2000-12-27 CZ CZ20022265A patent/CZ20022265A3/cs unknown
- 2000-12-27 CN CNB008192537A patent/CN100333790C/zh not_active Expired - Fee Related
- 2000-12-27 WO PCT/US2000/035452 patent/WO2001049274A2/fr not_active Ceased
- 2000-12-27 SK SK1114-2002A patent/SK11142002A3/sk not_active Application Discontinuation
- 2000-12-27 HU HU0204136A patent/HUP0204136A3/hu unknown
- 2000-12-27 JP JP2001549642A patent/JP2003519175A/ja active Pending
- 2000-12-27 PL PL00356641A patent/PL356641A1/xx not_active Application Discontinuation
- 2000-12-27 IL IL15046100A patent/IL150461A0/xx active IP Right Grant
- 2000-12-27 BR BR0016879-3A patent/BR0016879A/pt not_active IP Right Cessation
- 2000-12-27 AU AU26037/01A patent/AU783795B2/en not_active Ceased
- 2000-12-27 NZ NZ520379A patent/NZ520379A/en unknown
- 2000-12-27 CA CA002395887A patent/CA2395887A1/fr not_active Abandoned
2002
- 2002-06-27 NO NO20023123A patent/NO20023123L/no not_active Application Discontinuation
- 2002-06-27 IL IL150461A patent/IL150461A/en not_active IP Right Cessation
2003
- 2003-04-07 US US10/408,648 patent/US20030198602A1/en not_active Abandoned
2007
- 2007-07-10 US US11/827,086 patent/US20080003294A1/en not_active Abandoned

Also Published As

Publication number	Publication date
CN100333790C (zh)	2007-08-29
NO20023123L (no)	2002-08-07
CZ20022265A3 (cs)	2004-01-14
EP1244432A2 (fr)	2002-10-02
US20030198602A1 (en)	2003-10-23
NZ520379A (en)	2004-05-28
PL356641A1 (en)	2004-06-28
NO20023123D0 (no)	2002-06-27
AU2603701A (en)	2001-07-16
HUP0204136A3 (en)	2005-09-28
HUP0204136A2 (hu)	2003-03-28
CA2395887A1 (fr)	2001-07-12
WO2001049274A3 (fr)	2002-02-14
AU783795B2 (en)	2005-12-08
CN1437466A (zh)	2003-08-20
JP2003519175A (ja)	2003-06-17
IL150461A0 (en)	2002-12-01
WO2001049274A2 (fr)	2001-07-12
IL150461A (en)	2008-11-26
US20080003294A1 (en)	2008-01-03
BR0016879A (pt)	2002-12-03

Legal Events

Date	Code	Title	Description
2011-05-06	FC9A	Refused patent application

Publication	Publication Date	Title
AU783795B2 (en)	2005-12-08	Methods for pulmonary delivery of interleukin-2
JP4338214B2 (ja)	2009-10-07	エリトロポエチンの肺投与
US6565841B1 (en)	2003-05-20	Pulmonary administration of granulocyte colony stimulating factor
US7300919B2 (en)	2007-11-27	Pulmonary delivery of active fragments of parathyroid hormone
EP0505123B1 (fr)	1997-01-08	Administration par voie pulmonaire de G-CSF
US6737045B2 (en)	2004-05-18	Methods and compositions for the pulmonary delivery insulin
US6720407B1 (en)	2004-04-13	Method for administering insulinotropic peptides
EP0477386A1 (fr)	1992-04-01	Formulation d'un aerosol a usage pharmaceutique comportant des microparticules solides de polypeptide et procede de preparation.
US20090203576A1 (en)	2009-08-13	Methods and compositons for pulmonary delivery of insulin
KR20060034216A (ko)	2006-04-21	응고 인자의 흡입에 의한 혈우병 치료
Siekmeier et al.	2009	Treatment of systemic diseases by inhalation of biomolecule aerosols
AU2006200923A1 (en)	2006-03-30	Methods for pulmonary delivery of interleukin-2
CN1853725A (zh)	2006-11-01	白细胞介素－2经肺部的输递方法