SK286981B6 - Prášok na použitie v inhalátore na suché prášky, nosič na tento prášok a spôsob výroby prášku - Google Patents

Prášok na použitie v inhalátore na suché prášky, nosič na tento prášok a spôsob výroby prášku Download PDF

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Publication number
SK286981B6
SK286981B6 SK1248-2001A SK12482001A SK286981B6 SK 286981 B6 SK286981 B6 SK 286981B6 SK 12482001 A SK12482001 A SK 12482001A SK 286981 B6 SK286981 B6 SK 286981B6
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SK
Slovakia
Prior art keywords
carrier
powder
magnesium stearate
particles
carrier particles
Prior art date
Application number
SK1248-2001A
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English (en)
Slovak (sk)
Other versions
SK12482001A3 (sk
Inventor
Rossella Musa
Paolo Ventura
Paolo Chiesi
Original Assignee
Chiesi Farmaceutici S.P.A.
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.)
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Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=8167234&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SK286981(B6) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Chiesi Farmaceutici S.P.A. filed Critical Chiesi Farmaceutici S.P.A.
Publication of SK12482001A3 publication Critical patent/SK12482001A3/sk
Publication of SK286981B6 publication Critical patent/SK286981B6/sk

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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
    • A61K9/0012—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/203—Retinoic acids ; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/231—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
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    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
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    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C07C45/298—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups with manganese derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
    • C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/38—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings
    • C07C47/47—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/72—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/734—Ethers

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Emergency Medicine (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Otolaryngology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
SK1248-2001A 1999-03-05 1999-03-05 Prášok na použitie v inhalátore na suché prášky, nosič na tento prášok a spôsob výroby prášku SK286981B6 (sk)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP1999/001449 WO2000053157A1 (en) 1999-03-05 1999-03-05 Improved powdery pharmaceutical compositions for inhalation

Publications (2)

Publication Number Publication Date
SK12482001A3 SK12482001A3 (sk) 2002-01-07
SK286981B6 true SK286981B6 (sk) 2009-08-06

Family

ID=8167234

Family Applications (1)

Application Number Title Priority Date Filing Date
SK1248-2001A SK286981B6 (sk) 1999-03-05 1999-03-05 Prášok na použitie v inhalátore na suché prášky, nosič na tento prášok a spôsob výroby prášku

Country Status (17)

Country Link
US (3) US6528096B1 (de)
EP (1) EP1158958B1 (de)
AT (1) ATE363892T1 (de)
AU (1) AU3409399A (de)
BR (1) BR9917246A (de)
CY (1) CY1106817T1 (de)
CZ (1) CZ298489B6 (de)
DE (1) DE69936268T2 (de)
DK (1) DK1158958T3 (de)
ES (1) ES2286881T3 (de)
HU (1) HUP0200185A3 (de)
PL (1) PL196951B1 (de)
PT (1) PT1158958E (de)
SI (1) SI1158958T1 (de)
SK (1) SK286981B6 (de)
TR (1) TR200102567T2 (de)
WO (1) WO2000053157A1 (de)

Families Citing this family (82)

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CZ303154B6 (cs) 1998-11-13 2012-05-09 Jagotec Ag Suchá prášková formulace k inhalaci obsahující stearát horecnatý
DZ2947A1 (fr) 1998-11-25 2004-03-15 Chiesi Farma Spa Inhalateur à compteur de dose sous pression.
IT1309592B1 (it) * 1999-03-05 2002-01-24 Chiesi Farma Spa Particelle veicolo modificate da utilizzarsi nella preparazione diformulazioni farmaceutiche sotto forma di polimeri per inalazione e
US9006175B2 (en) 1999-06-29 2015-04-14 Mannkind Corporation Potentiation of glucose elimination
ITMI991582A1 (it) 1999-07-16 2001-01-16 Chiesi Farma Spa Polveri costituite da particelle aventi la superficie perfettamente levigata da utilizzare come veicoli per la preparazione di miscele inala
IT1313553B1 (it) 1999-07-23 2002-09-09 Chiesi Farma Spa Formulazioni ottimizzate costituite da soluzioni di steroidi dasomministrare per inalazione.
IT1317846B1 (it) 2000-02-22 2003-07-15 Chiesi Farma Spa Formulazioni contenenti un farmaco anticolinergico per il trattamentodella broncopneumopatia cronica ostruttiva.
GB0009469D0 (en) 2000-04-17 2000-06-07 Vectura Ltd Improvements in or relating to formalities for use in inhaler devices
PE20011227A1 (es) 2000-04-17 2002-01-07 Chiesi Farma Spa Formulaciones farmaceuticas para inhaladores de polvo seco en la forma de aglomerados duros
GB0009468D0 (en) * 2000-04-17 2000-06-07 Vectura Ltd Improvements in or relating to formulations for use in inhaler devices
IT1318514B1 (it) * 2000-05-12 2003-08-27 Chiesi Farma Spa Formulazioni contenenti un farmaco glucocorticosteroide per iltrattamento di patologie broncopolmonari.
JP5392880B2 (ja) 2000-05-22 2014-01-22 キエシ・フアルマチエウテイチ・ソチエタ・ペル・アチオニ 加圧式定量吸入器のための安定な製薬学的溶液製剤
WO2002043700A2 (en) 2000-11-30 2002-06-06 Vectura Limited Particles for use in a pharmaceutical composition
NZ526059A (en) † 2000-11-30 2005-05-27 Vectura Ltd Method of making composite active particles in the presence of an additive material for use in a pharmaceutical composition
EP2283818B1 (de) 2000-11-30 2017-08-02 Vectura Limited Herstellungsverfahren für Partikel zur Verwendung in einer Arrzneizusammensetzung
WO2003024396A2 (en) 2001-09-17 2003-03-27 Glaxo Group Limited Dry powder medicament formulations
EP1494732B1 (de) 2002-03-20 2008-01-30 MannKind Corporation Inhalationsgerät
EP1494652A1 (de) * 2002-04-12 2005-01-12 Campina Nederland Holding B.V. Hilfsstoff zur verwendung in trockenpulver-inhalationszubereitungen
US8273331B2 (en) 2002-08-21 2012-09-25 Norton Healthcare Ltd. Inhalation compositions
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GB0219511D0 (en) * 2002-08-21 2002-10-02 Norton Healthcare Ltd Method of preparing dry powder inhalation compositions
JP2006516531A (ja) * 2002-08-21 2006-07-06 ノートン　ヘルスケアー　リミテッド 吸入組成物
CN102688224A (zh) * 2003-04-14 2012-09-26 维克特拉有限公司 用于提高剂量效率的药物组合物和装置
US20050042179A1 (en) * 2003-08-18 2005-02-24 Boehringer Ingelheim International Gmbh Inhalative powder formulations containing the CGRP-antagonist 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine
GB0326632D0 (en) 2003-11-14 2003-12-17 Jagotec Ag Dry powder formulations
KR101273120B1 (ko) 2004-08-20 2013-06-13 맨카인드 코포레이션 다이케토피페라진 합성의 촉매 작용
KR20130066695A (ko) 2004-08-23 2013-06-20 맨카인드 코포레이션 약물 전달용 디케토피페라진염, 디케토모르포린염 또는 디케토디옥산염
GB0425758D0 (en) 2004-11-23 2004-12-22 Vectura Ltd Preparation of pharmaceutical compositions
WO2007001094A1 (ja) * 2005-06-29 2007-01-04 Sannamu Lee 人工肺サーファクタント組成物
WO2007030227A2 (en) * 2005-07-29 2007-03-15 The Board Of Governors For Higher Education, Modified oligonucleotides containing diphosphodiester internucleotide linkages
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ES2286881T3 (es) 2007-12-01
EP1158958A1 (de) 2001-12-05
SK12482001A3 (sk) 2002-01-07
PT1158958E (pt) 2007-08-13
DE69936268D1 (de) 2007-07-19
CY1106817T1 (el) 2012-05-23
AU3409399A (en) 2000-09-28
TR200102567T2 (tr) 2002-01-21
SI1158958T1 (sl) 2007-10-31
WO2000053157A1 (en) 2000-09-14
US6528096B1 (en) 2003-03-04
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HUP0200185A3 (en) 2006-07-28
DK1158958T3 (da) 2007-10-08
US20030133880A1 (en) 2003-07-17
DE69936268T2 (de) 2008-02-14
PL354841A1 (en) 2004-02-23
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PL196951B1 (pl) 2008-02-29
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