JP6067047B2 - 薬物動態の改善のためのエアゾールフルオロキノロン配合物 - Google Patents
薬物動態の改善のためのエアゾールフルオロキノロン配合物 Download PDFInfo
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- JP6067047B2 JP6067047B2 JP2015063052A JP2015063052A JP6067047B2 JP 6067047 B2 JP6067047 B2 JP 6067047B2 JP 2015063052 A JP2015063052 A JP 2015063052A JP 2015063052 A JP2015063052 A JP 2015063052A JP 6067047 B2 JP6067047 B2 JP 6067047B2
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Description
「投与」または「投与する」という用語は、抗菌性医薬組成物の用量を脊椎動物に与える方法を意味する。好ましい投与方法は、様々な因子、例えば、医薬組成物の構成物、潜在的なまたは実際の細菌感染症の部位、関与する微生物および実際の微生物感染の重症度に応じて変わり得る。
抗生物質の死滅率は、抗生物質の作用機序に依存しており、死滅させるために抗生物質に必要な時間の長さ(時間依存性)または抗生物質濃度を増加させる効果(濃度依存性)によって決定される。フルオロキノロンは、治療効果が感染している病原体のMICを超える高い局所ピーク濃度を必要とする場合に濃度依存性の、時間-死滅活性によって特徴付けられる。
いくつかの実施形態では、方法は、このような肺感染症に罹患した動物を二価または三価陽イオンと共に配合されたおよび肺利用率の改善を有するフルオロキノロン抗菌剤で治療することにより、具体的には哺乳動物を含めた動物において微生物感染を治療するために提供される。いくつかの実施形態では、フルオロキノロン抗菌剤は、エアゾール形成および吸入後に投与することができる。したがって、この治療の方法は、(望ましくない副作用を引き起こし得る)高用量レベルの必要性により、または任意の臨床的に有効な抗菌剤の欠如により、経口もしくは非経口で送達される抗菌剤を用いて治療することが難しい微生物株が関与する肺感染症の治療に特に適切である。かかる一実施形態では、この方法は、フルオロキノロン抗菌剤を感染部位に直接投与するために用いることができる。このような方法は、全身曝露を低減し、微生物感染部位への抗菌剤の量を最大限にすることができる。この方法はまた、抵抗性の微生物の選択の頻度を低減するやり方として、フルオロキノロン抗菌剤に感受性である微生物が関与する感染症を治療するために適切である。この方法はまた、微生物感染部位で抗菌剤の量を増加するやり方として、他の点でフルオロキノロン抗菌剤に抵抗性である微生物に関与する感染症を治療するために適切である。対象は、抵抗性株を有することが知られている細菌種による細菌感染症または抵抗性株を有することが知られている群のメンバーである細菌による細菌感染症に特徴的である症状を有するものとして対象を診断することにより、抵抗性を発生することのできる細菌による感染者として同定することができる。あるいは、細菌は、培養することができ、抵抗性株を有することが知られている種または抵抗性株を有することが知られている群のメンバーである細菌として同定することができる。
本明細書に記載した方法の目的のために、改善された肺利用率を有する二価または三価陽イオンと共に配合されたフルオロキノロン抗菌剤は、吸入器を用いて投与することができる。いくつかの実施形態では、本明細書に開示されるフルオロキノロン抗菌剤は、エアゾール形成、味の良さ、貯蔵安定性、ならびに患者の安全性および忍容性に適当な医薬組成物として生成される。いくつかの実施形態では、製造されたフルオロキノロンのアイソフォーム含有量は、忍容性、抗菌活性および安定性のために最適化することができる。
二価または三価陽イオンと共に配合され、改善された肺利用率を有するフルオロキノロン抗菌剤は、治療上有効な用量、例えば、前述した病態に治療を提供するのに十分な用量で投与することができる。投与される活性化合物の量は、もちろん、治療される対象および病態、病気の重症度、投与の方式およびスケジュールおよび処方医の判断に依存し;例えば、レボフロキサシンのエアゾール投与のためのありそうな用量範囲は、1日約20〜300mgになるはずであり、有効な薬剤はそれぞれ、より長期のもしくはより短期の肺半減期のために選択される。いくつかの実施形態では、レボフロキサシンのエアゾール投与のためのありそうな用量範囲は、約20〜300mg BID(1日2回)となるはずである。
肺投与の場合、上気道は、中間および下気道のために避けられる。肺薬物送達は、口および咽頭によりエアゾールの吸入によって達成することができる。約5ミクロンを超える空気動力学的粒子中央径(MMAD)を有する粒子は、一般に、肺に到達せず;代わりに、これらは、咽頭の裏に影響する傾向があり、嚥下され、おそらく、経口的に吸収される。直径約2〜約5ミクロンを有する粒子は、(気道を導く)上部から中間部の肺領域に到達するほど小型であるが、肺胞に到達するには大きすぎる。より小型の粒子、すなわち約0.5〜約2ミクロンは、肺胞領域に到達することができる。約0.5ミクロンよりも小型の直径を有する粒子は、非常に小型の粒子は発散され得るが、沈降により肺胞領域中に堆積させることもできる。
本明細書に記載した方法および組成物は、肺感染症および障害を治療するために用いることができる。かかる障害の例は、嚢胞性線維症、肺炎、および慢性気管支炎を含めた慢性閉塞性肺疾患、およびいくつかの喘息を含むことができる。いくつかの実施形態には、緑膿菌、蛍光菌(Pseudomonas fluorescens)、シュードモナス・アシドボランス(Pseudomonas acidovorans)、シュードモナス・アルカリゲネス(Pseudomonas alcaligenes)、プチダ菌(Pseudomonas putida)、ステノトロホモナス・マルトフィリア(Stenotrophomonas maltophilia)、エロモナス・ハイドロフイラ(Aeromonas hydrophilia)、大腸菌(Escherichia coli)、シトロバクター・フロインデイ(Citrobacter freundii)、ネズミチフス菌(Salmonella typhimurium)、チフス菌(Salmonella typhi)、パラチフス菌(Salmonella paratyphi)、腸炎菌(Salmonella enteritidis)、志賀赤痢菌(Shigella dysenteriae)、シゲラ・フレックスネリ(Shigella flexneri)、ソンネ菌(Shigella sonnei)、エンテロバクター・クロアカ(Enterobacter cloacae)、エンテロバクター・エロゲネス(Enterobacter aerogenes)、肺炎桿菌(Klebsiella pneumoniae)、クレブシエラ・オキシトカ(Klebsiella oxytoca)、霊菌(Serratia marcescens)、モルガン菌(Morganella morganii)、プロテウス・ミラビリス(Proteus mirabilis)、プロテウス・ブルガリス(Proteus vulgaris)、プロビデンシア・アルカリファシエンス(Providencia alcalifaciens)、プロビデンシア・レットゲリ(Providencia rettgeri)、プロビデンシア・スチュアルティイ(Providencia stuartii)、アシネトバクター・カルコアセティカス(Acinetobacter calcoaceticus)、アシネトバクター・ヘモリティカス(Acinetobacter haemolyticus)、エンテロコリチカ菌(Yersinia enter ocolitica)、ペスト菌(Yersinia pestis)、仮性結核菌(Yersinia pseudotuberculosis)、エルシニア・インターメディア(Yersinia intermedia)、百日咳菌(Bordetella pertussis)、パラ百日咳菌(Bordetella parapertussis)、ボルデテラ・ブロンキセプチカ(Bordetella bronchiseptica)、インフルエンザ菌(Haemophilus influenzae)、パラインフルエンザ菌(Haemophilus parainfluenzae)、ヘモフィラス・ヘモリティカス(Haemophilus haemolyticus)、ヘモフィラス・パラヘモリティカス(Haemophilus parahaemolyticus)、軟性下疳菌(Haemophilus ducreyi)、パスツレラ・マルトシダ(Pasteurella multocida)、ヘモリチカ菌(Pasteurella haemolytica)、ピロリ菌(Helicobacter pylori)、カンピロバクター・フィタス(Campylobacter fetus)、カンピロバクター・ジェジュニ(Campylobacter jejuni)、カンピロバクター・コリ(Campylobacter coli)、ボレリア・ブルグドルフェリ(Borrelia burgdorferi)、コレラ菌(Vibrio cholera)、腸炎ビブリオ(Vibrio parahaemolyticus)、在郷軍人病菌(Legionella pneumophila)、リステリア菌(Listeria monocytogenes)、淋菌(Neisseria gonorrhoeae)、髄膜炎菌(Neisseria meningitidis)、セパシア菌(Burkholderia cepacia)、野兎病菌(Francisella tularensis)、キンゲラ(Kingella)、およびモラクセラ(Moraxella)からなる群から選択される1種または複数の細菌を含む感染症を
治療することが含まれる。いくつかの実施形態では、肺感染症は、グラム陰性嫌気性菌によって引き起こされる。さらなる実施形態では、肺感染症は、バクテロイデス・フラジリス(Bacteroides fragilis)、バクテロイデス・ディスタソニス(Bacteroides distasonis)、バクテロイデス3452Aホモロジー群、バクテロイデス・ブルガタス(Bacteroides vulgatus)、バクテロイデス・オバータス(Bacteroides ovalus)、バクテロイデス・テタイオタオミクロン(Bacteroides thetaiotaomicron)、バクテロイデス・ユニフォルミス(Bacteroides uniformis)、バクテロイデス・エガーシイ(Bacteroides eggerthii)、およびバクテロイデス・スプランクニクス(Bacteroides splanchnicus)からなる群から選択される細菌の1種または複数を含む。いくつかの実施形態では、肺感染症は、グラム陽性菌によって引き起こされる。いくつかの実施形態では、肺感染症は、ジフテリア菌(Corynebacterium diphtheriae)、コリネバクテリウム・ウルセランス(Corynebacterium ulcerans)、肺炎球菌(Streptococcus pneumoniae)、ストレプトコッカス・アガラクチア(Streptococcus agalactiae)、化膿性連鎖球菌(Streptococcus pyogenes)、ストレプトコッカス・ミレリ群(Streptococcus milleri);ストレプトコッカス(Streptococcus)(グループG);ストレプトコッカス(グループC/F);エンテロコッカス・フェカリス(Enterococcus faecalis)、フェシウム菌(Enterococcus faecium)、黄色ブドウ球菌(Staphylococcus aureus)、表皮ブドウ球菌(Staphylococcus epidermidis)、スタフィロコッカス・サプロフィチカス(Staphylococcus saprophyticus)、スタフィロコッカス・インターメディウス(Staphylococcus intermedius)、スタフィロコッカス・ヒカス亜種ヒカス(Staphylococcus hyicus subsp. hyicus)、スタフィロコッカス・ヘモリチカス(Staphylococcus haemolyticus)、スタフィロコッカス・ホミニス(Staphylococcus hominis)、およびスタフィロコッカス・サッカロリティカス(Staphylococcus saccharolyticus)からなる群から選択される細菌の1種または複数を含む。いくつかの実施形態では、肺感染症は、グラム陽性嫌気性菌によって引き起こされる。いくつかの実施形態では、肺感染症は、クロストリジウム・ディフィシル(Clostridium difficile)、ウェルシュ菌(Clostridium perfringens)、クロストリジウム・テタニ(Clostridium tetini)、およびボツリヌス菌(Clostridium botulinum)からなる群から選択される1種または複数の細菌によって引き起こされる。いくつかの実施形態では、肺感染症は、抗酸菌によって引き起こされる。いくつかの実施形態では、肺感染症は、結核菌(Mycobacterium tuberculosis)、マイコバクテリウム・アビウム(Mycobacterium avium)、マイコバクテリウム・イントラセルラーレ(Mycobacterium intracellulare)、およびらい菌(Mycobacterium leprae)からなる群から選択される1種または複数の細菌によって引き起こされる。いくつかの実施形態では、肺感染症は、異型細菌によって引き起こされる。いくつかの実施形態では、肺感染症は、クラミジア・ニューモニエ(Chlamydia pneumoniae)および肺炎マイコプラズマ(Mycoplasma pneumoniae)からなる群から選択される1種または複数の細菌によって引き起こされる。
(比較例1)
ラット薬物動態モデルにおけるフルオロキノロンの投与
この実施例は、食塩水中フルオロキノロンのエアゾールおよび静脈内投与に関する。ラット薬物動態モデルを用いてフルオロキノロンの静脈内投与および肺投与を比較した。スプラーグドーリー系雄ラット(Charles Rivers)に、レボフロキサシン、シプロフロキサシン、ガチフロキサシン、ノルフロキサシン、またはゲミフロキサシン10mg/kg用量を投与した。用量を、外側尾静脈によって、または気管分岐部より上の肺にマイクロスプレーエアゾールデバイス(Penn Century、Philadelphia、PA)を用いて投与した。レボフロキサシンを無菌の0.9%食塩水中で5mg/ml(IV)および60mg/ml(エアゾール)の濃度に調製した。
ラットにおける二価陽イオンを有するレボフロキサシンのエアゾール投与
この実施例は、二価陽イオンおよび乳糖を有するレボフロキサシンのエアゾール投与および食塩水中のレボフロキサシンのIVもしくはエアゾール投与を含む一連の研究に関する。ラットに食塩水中の10mg/kgレボフロキサシン(LVX)またはCaCl2、MgCl2、もしくはZn+2と共に配合されたLVXを投与した。Table 2(表2)は、これらの試験に使用されるレボフロキサシンの配合物を示す。
薬物動態モデリングおよびデコンボリューション分析
この実施例は、肺における薬物濃度をモデル化することに関する。薬物動態学的デコンボリューション法は、投与後に肺に残存する薬物の量を決定するのに有用である。かかる方法は、直接測定が難しいおよび/または例えば、痰サンプルを用いて肺の薬物濃度を測定し可変の結果を出す場合、特に有用である。
食塩水を含むレボフロキサシンのエアゾールおよび全身投与
この実施例は、レボフロキサシンの推定される吸入可能な薬物用量20mgまたは40mg(ネビュライザーに添加される用量がそれぞれ43.3mgおよび86.6mg)を用いて食塩水中に配合されたレボフロキサシンのエアゾールおよび全身投与に関する。(IV配合物Levaquin(登録商標)を用いて)レボフロキサシンの2つの用量レベルの単回エアゾール用量を、正常な健常ボランティアおよび安定性CF対象に、PARI eFlow高効率ネビュライザーを用いて投与した。
MgCl2と共に配合されたレボフロキサシンの30mg/mlおよび50mg/ml溶液のエアゾール投与
この実施例は、MgCl2と共に配合されたレボフロキサシンの30mg/mlおよび50mg/ml溶液のCF患者へのエアゾール投与に関する。Table 11(表11)は、MgCl2および乳糖を有するレボフロキサシンの配合物を示す。
CF患者における食塩水またはMgCl2中で配合されるレボフロキサシンの40mgRDDのエアゾール投与の比較
この実施例は、40mgレボフロキサシンの推定される吸入可能な薬物用量(RDD)を用いたMgCl2を有するまたは食塩水中のレボフロキサシンのエアゾール投与に関する。食塩水中のレボフロキサシンの濃度は、MgCl2/乳糖を含む配合物中で23.8mg/mlおよび30mg/mlである(Table 11(表11)を参照のこと)。CF患者は、エアゾール送達によるレボフロキサシンの40mg吸入可能な薬物用量を受けた。すなわち、7名の患者は、食塩水中で配合されたレボフロキサシンを受け;10名の患者は、同様の推定されるRDDを受け、MgCl2と共に配合されたレボフロキサシンを受けた。痰サンプルを、24時間までの様々な時間で採取し、レボフロキサシン濃度は、HPLC/蛍光法を用いて決定した。経時的に痰中で測定された平均レボフロキサシン濃度を図11に示す。MgCl2により送達されるレボフロキサシンは、食塩水中で送達されるレボフロキサシンの同様の用量よりも長期間および高濃度で痰中で保持される。
14日までの間の乳糖を加えたMgCl2を含む配合物のエアゾール投与後のCF患者におけるレボフロキサシンの薬物動態
CF患者は、1日目に治療当たりおよそ40mg、80mg、または120mgの吸入可能な送達量(治療当たり添加された用量78mg、175mg、または260mg)を受け、その後1日2回投与を14日間受けた。Table 11(表11)に示される配合物を用いた。標準的な非コンパートメントおよびコンパートメントPK法を用いて血清、痰、および泌尿器のPKパラメーターを生成した(その全体が参照により本明細書に組み込まれる、Gibaldi M、Perrier B. Pharmacokinetics.第2版 New York:Marcel-Dekker;1982年)。PKパラメーターを血清および痰について決定し、それぞれTable 13(表13)およびTable 14(表14)に示す。食塩水中のレボフロキサシンの投与との比較(実施例4)により、有意により高い痰CmaxおよびAUCが共にマグネシウムとの複合体形成によって達成されることが示される(例えば、Cmaxはレボフロキサシン211.5mg/L対レボフロキサシン:Mgで448.97mg/Lであり、AUCは、40mg吸入可能な用量の場合、レボフロキサシン171.4時間.mg/L対レボフロキサシン:Mg(1日目)420.54時間.mg/Lである)。
MgCl2と共に配合されたレボフロキサシンの50mg/mlおよび100mg/ml溶液のエアゾール投与
この実施例は、MgCl2と共に配合されたレボフロキサシンの50mg/mlおよび100mg/ml溶液を180mgおよび240mgの用量でCF患者にエアゾール投与することに関する。Table 15(表15)は、MgCl2を有するレボフロキサシンの配合物を示す。
マウス肺感染症モデル
マウス肺感染症モデルを用いて静脈内投与の効力をフルオロキノロンの肺投与と比較した。1群当たり8匹のマウスを、気管内滴下注入によって肺炎桿菌ATCC 43816に感染させた。感染後24時間、マウスに、マイクロスプレーエアゾール生成デバイス(PennCentury、Philadelphia、PA)を用いてエアゾール用量10または20mg/kgを1日2回(BID)投与した。治療開始後24時間、動物を屠殺し肺を除去し、ホモジナイズし、蒔いてコロニー数を決定した。Table 20(表20)は、この試験に用いた配合物を示す。
マウス肺感染症モデルにおけるMgCl2と共に配合されたエアゾールレボフロキサシンの効果
この実施例は、MgCl2を有するレボフロキサシンのエアゾール投与および食塩水中のレボフロキサシンの腹腔内投与に関する。以下の試験の目的は、緑膿菌による急性および慢性肺感染症モデルにおけるこれらの療法の効果を決定することであった。
動物試験に用いた緑膿菌株の最小生育阻止濃度(MIC)をTable 22(表22)に示す。トブラマイシンは、<1μg/mlのMICを有するin vitroで最も強力な抗生物質であり、MgCl2と共に配合されたレボフロキサシンおよびレボフロキサシンは、1および2μg/mlのMICを有し、アズトレオナムは、両方の株に対して4μg/mlのMICを有した。
MgCl2と共に配合されたレボフロキサシンおよびレボフロキサシンの標準化された肺薬物動態パラメーターをTable 23(表23)に示す。60mg/kgのMgCl2と共に配合されたレボフロキサシンをエアゾール投与すると、レボフロキサシンの用量を標準化した腹腔内投与で達成されたものよりも9倍および30倍高かったレボフロキサシンAUCおよびCmaxの値を生成した。
急性肺感染症モデルにおいて、MgCl2と共に配合されたレボフロキサシン125mg/kg、62.5mg/kg、および32mg/kgによるエアゾール治療はそれぞれ、肺細菌数の5.9log CFU、4.3log CFU、および2.3log CFUの減少をもたらした(図16)。レボフロキサシン125mg/kg、62.5mg/kg、および32mg/kgによる全身治療はそれぞれ、3.5log CFU、2.7log CFU、および0.65 log CFUの減少をもたらした。MgCl2と共に配合されたエアゾールレボフロキサシンによる細菌数の減少は、用量当たりでIPレボフロキサシンで観察されたものより大きかった(p<0.05)。
急性肺感染症モデルにおけるMgCl2と共に配合されたレボフロキサシン、トブラマイシンおよびアズトレオナムの効果を比較するために、マウスを、緑膿菌ATCC27853に感染させ、エアゾール経路により1日2回連続2日間治療した。毒性により、トブラマイシンを60mg/kgの最大用量に制限し、アズトレオナムを400mg/kgの最大用量に制限した。さらに、治療用の麻酔を必要とするため、最大1日量の数値を2に制限した。
MgCl2と共に配合されたエアロゾル化したレボフロキサシン、トブラマイシンおよびアズトレオナムはそれぞれ、3.3、2.9、および1.25の平均log CFUの減少をもたらした(図20)。トブラマイシンまたはMgCl2と共に配合されたレボフロキサシンのエアロゾル化した用量は、アズトレオナム,または未治療対照群に比べて有意に低い細菌数をもたらした(p<0.05)。
Claims (9)
- 嚢胞性線維症を有する患者における肺の緑膿菌細菌感染の治療において使用し、90mg/ml〜110mg/mlのレボフロキサシンおよび180mM〜220mMのマグネシウム陽イオンを含む溶液のエアゾールであって、前記溶液は240mgのレボフロキサシンを含み、pH5〜7および重量オスモル濃度300mOsmol/kg〜500mOsmol/kgを有し、前記エアゾールは幾何標準偏差2.5ミクロン以下を有する空気動力学的粒子中央径2ミクロン〜5ミクロンを有する、エアゾール。
- 前記溶液が前記マグネシウム陽イオンの供給源として塩化マグネシウムを含む、請求項1に記載のエアゾール。
- 前記溶液が、重量オスモル濃度350mOsmol/kg〜425mOsmol/kg、およびpH 5〜6.5を含む、請求項1または2に記載のエアゾール。
- 前記溶液が、レボフロキサシン濃度90mg/ml〜110mg/ml、塩化マグネシウム濃度190mM〜210mMを含む、請求項2に記載のエアゾール。
- 90mg/ml〜110mg/mlのレボフロキサシンおよび180mM〜220mMのマグネシウム陽イオンを含む水溶液を含む医薬組成物であって、前記溶液が、pH5〜7および重量オスモル濃度300mOsmol/kg〜500mOsmol/kgを有し、前記溶液は240mgのレボフロキサシンを含む医薬組成物。
- 前記溶液が、pH6.0〜6.5および重量オスモル濃度350mOsmol/kg〜400mOsmol/kgを有する、請求項5に記載の組成物。
- 前記溶液が、90mg/ml〜110mg/mlのレボフロキサシンおよび190mM〜210mMのマグネシウム陽イオンを含む、請求項5または6に記載の組成物。
- 前記マグネシウム陽イオンが塩化マグネシウムである、請求項5から7のいずれか一項に記載の組成物。
- 前記溶液が、100mg/mlのレボフロキサシンおよび200mMの塩化マグネシウムを含み、pH6.0〜6.5および重量オスモル濃度350mOsmol/kg〜400mOsmol/kgを有する、請求項8に記載の組成物。
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Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2887054T3 (es) | 2003-04-11 | 2021-12-21 | Ptc Therapeutics Inc | Compuesto de ácido 1,2,4-oxadiazol benzoico y su uso para la supresión sin sentido y el tratamiento de enfermedades |
US8524734B2 (en) * | 2005-05-18 | 2013-09-03 | Mpex Pharmaceuticals, Inc. | Aerosolized fluoroquinolones and uses thereof |
PT1993360T (pt) | 2005-12-28 | 2017-05-25 | Vertex Pharma | Formas sólidas de n-[2,4-bis(1,1-dimetiletil)-5-hidroxifenil]-1,4-di-hidro-4-oxoquinolina-3-carboxamida |
JP2012505222A (ja) * | 2008-10-07 | 2012-03-01 | エムペックス・ファーマシューティカルズ・インコーポレーテッド | 肺炎症を低減するためのレボフロキサシンの吸入 |
JP2012505223A (ja) | 2008-10-07 | 2012-03-01 | エムペックス・ファーマシューティカルズ・インコーポレーテッド | 薬物動態の改善のためのエアゾールフルオロキノロン配合物 |
HUE046595T2 (hu) * | 2009-04-24 | 2020-03-30 | Horizon Orphan Llc | Eljárások bakteriális tüdõfertõzés kezelésére fluorokinolonok alkalmazásával |
EP2467138A4 (en) * | 2009-08-19 | 2013-11-06 | Mpex Pharmaceuticals Inc | USE OF AEROSOLIZED ANTIBIOTICS FOR THE TREATMENT OF CHRONIC OBSTRUCTIVE LUNG DISEASE |
AU2010289326B2 (en) * | 2009-09-04 | 2015-09-24 | Horizon Therapeutics U.S. Holding Llc | Use of aerosolized levofloxacin for treating cystic fibrosis |
AU2015275224C1 (en) * | 2009-09-04 | 2017-11-16 | Horizon Therapeutics U.S. Holding Llc | Use of aerosolized levofloxacin for treating cystic fibrosis |
HUE058753T2 (hu) * | 2011-01-31 | 2022-09-28 | Avalyn Pharma Inc | Aeroszol formájú pirfenidon- és piridon-analóg vegyületek és alkalmazásaik |
US10105356B2 (en) | 2011-01-31 | 2018-10-23 | Avalyn Pharma Inc. | Aerosol pirfenidone and pyridone analog compounds and uses thereof |
US9572774B2 (en) | 2011-05-19 | 2017-02-21 | Savara Inc. | Dry powder vancomycin compositions and associated methods |
KR101763195B1 (ko) * | 2011-05-19 | 2017-07-31 | 사바라 인코포레이티드 | 건조 분말 반코마이신 조성물 및 관련 방법 |
CN103917223B (zh) | 2011-09-14 | 2017-08-08 | 盐野义制药株式会社 | 供吸入的药用组合物 |
NZ705260A (en) * | 2012-07-24 | 2017-04-28 | Genoa Pharmaceuticals Inc | Aerosol pirfenidone and pyridine analog compounds for the treatment of lung disease |
JP6472807B2 (ja) * | 2013-09-12 | 2019-02-20 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 嚢胞性線維症の処置のための方法及び医薬組成物 |
NZ722927A (en) | 2014-01-10 | 2022-07-29 | Avalyn Pharma Inc | Aerosol pirfenidone and pyridone analog compounds and uses thereof |
EP2896400A1 (en) | 2014-01-17 | 2015-07-22 | Université Catholique De Louvain | Method for increasing the bioavailability of inhaled compounds |
CA2942147C (en) | 2014-03-06 | 2022-12-13 | Ptc Therapeutics, Inc. | Pharmaceutical compositions and salts of a 1,2,4-oxadiazole benzoic acid |
US9701639B2 (en) | 2014-10-07 | 2017-07-11 | Vertex Pharmaceuticals Incorporated | Co-crystals of modulators of cystic fibrosis transmembrane conductance regulator |
US20160108406A1 (en) * | 2014-10-08 | 2016-04-21 | University Of Iowa Research Foundation | Method of regulating cftr expression and processing |
BR112018008838A8 (pt) | 2015-10-30 | 2019-02-26 | Ptc Therapeutics Inc | método para tratar, prevenir, melhorar ou administrar uma doença epiléptica |
CN109486739B (zh) * | 2018-11-23 | 2022-02-01 | 上海海洋大学 | 一种诱导副溶血性弧菌产生左氧氟沙星耐药性的方法 |
CN109742110B (zh) * | 2019-01-04 | 2022-07-08 | 京东方科技集团股份有限公司 | 有机发光显示器及制造方法 |
CN110141569B (zh) * | 2019-06-13 | 2021-09-24 | 吉林大学 | 抗牛多杀性巴氏杆菌的药物组合物 |
Family Cites Families (265)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US696219A (en) | 1901-08-23 | 1902-03-25 | Paul Willemain | Building containing acetylene-gas-generating apparatus. |
US2587215A (en) * | 1949-04-27 | 1952-02-26 | Frank P Priestly | Inhalator |
BE555319A (ja) * | 1956-03-21 | 1900-01-01 | ||
US2858691A (en) | 1956-09-04 | 1958-11-04 | Mosler Lock Company | Key changed tumbler clamp |
BE556587A (ja) | 1957-01-31 | 1957-04-11 | ||
GB901107A (en) | 1959-06-29 | 1962-07-11 | Pfizer | Therapeutic composition and method of preparing same |
US3669113A (en) * | 1966-03-07 | 1972-06-13 | Fisons Ltd | Inhalation device |
US3507277A (en) * | 1966-09-17 | 1970-04-21 | Fisons Pharmaceuticals Ltd | Inhalation device |
US3456644A (en) | 1967-01-19 | 1969-07-22 | Dart Ind Inc | Inhalation-actuated aerosol dispensing device |
US3456646A (en) | 1967-01-19 | 1969-07-22 | Dart Ind Inc | Inhalation-actuated aerosol dispensing device |
US3456645A (en) | 1967-01-19 | 1969-07-22 | Dart Ind Inc | Inhalation-actuated aerosol dispensing device |
GB1268051A (en) * | 1968-06-07 | 1972-03-22 | Fisons Pharmaceuticals Ltd | Inhalation device |
US3565070A (en) * | 1969-02-28 | 1971-02-23 | Riker Laboratories Inc | Inhalation actuable aerosol dispenser |
US3636949A (en) * | 1969-08-08 | 1972-01-25 | Armstrong Kropp Dev Corp | Inhalation-initiated aerosol dispenser |
BE758834A (fr) | 1969-11-13 | 1971-05-12 | Riker Laboratoires Inc | Distributeur d'aerosol actionne par inhalation |
GB1383761A (en) * | 1971-02-25 | 1974-02-12 | Woodcraft Dc | Inhalation device for use with an aerosol container |
US3732864A (en) * | 1971-06-07 | 1973-05-15 | Schering Corp | Inhalation coordinated aerosol dispensing device |
IT941426B (it) * | 1971-07-17 | 1973-03-01 | Isf Spa | Inalatore a camera di turbinio per sostanze medicamentose polveriformi |
US3826255A (en) | 1972-06-22 | 1974-07-30 | Hudson Oxygen Therapy Sales Co | Intermittent positive pressure breathing manifold |
FR2224175B1 (ja) | 1973-04-04 | 1978-04-14 | Isf Spa | |
IT1016489B (it) | 1974-03-18 | 1977-05-30 | Isf Spa | Inalatore |
US3971377A (en) | 1974-06-10 | 1976-07-27 | Alza Corporation | Medicament dispensing process for inhalation therapy |
IT1017153B (it) * | 1974-07-15 | 1977-07-20 | Isf Spa | Apparecchio per inalazioni |
YU41046B (en) | 1974-08-22 | 1986-10-31 | Schering Ag | Medicine inholating device |
SU628930A1 (ru) | 1974-11-26 | 1978-10-25 | Московский научно-исследовательский институт туберкулеза | Устройство дл введени порошкообразного лекарственного вещества |
US3948264A (en) * | 1975-05-21 | 1976-04-06 | Mead Johnson & Company | Inhalation device |
US4147166A (en) * | 1977-05-02 | 1979-04-03 | American Cyanamid Company | Oral inhalator powder dispenser |
US4268460A (en) * | 1977-12-12 | 1981-05-19 | Warner-Lambert Company | Nebulizer |
US4253468A (en) * | 1978-08-14 | 1981-03-03 | Steven Lehmbeck | Nebulizer attachment |
US4263907A (en) * | 1979-05-14 | 1981-04-28 | Lindsey Joseph W | Respirator nebulizer |
BR8007911A (pt) | 1979-12-06 | 1981-06-16 | Glaxo Group Ltd | Inalador aperfeicoado |
JPS5746986A (en) | 1980-09-02 | 1982-03-17 | Dai Ichi Seiyaku Co Ltd | Pyrido(1,2,3-de)(1,4)benzoxazine derivative |
SI8110592A8 (en) | 1981-03-06 | 1996-06-30 | Pliva Pharm & Chem Works | Process for preparing of n-methyl-11-aza-10-deoxo-10-dihydroerythromycine a and derivatives thereof |
SE438261B (sv) * | 1981-07-08 | 1985-04-15 | Draco Ab | Anvendning i dosinhalator av ett perforerat membran |
US4688218A (en) | 1981-07-15 | 1987-08-18 | Etablissement Public De Diffusion Dit "Telediffusion De France" | Multiplex channels for continuous flow for numerical signal |
US4470412A (en) | 1982-03-19 | 1984-09-11 | Trutek Research, Inc. | Inhalation valve |
US4510929A (en) * | 1982-04-30 | 1985-04-16 | Bordoni Maurice E | Disposable radioactive aerosol inhalation apparatus |
US4730000A (en) * | 1984-04-09 | 1988-03-08 | Abbott Laboratories | Quinoline antibacterial compounds |
US4994599A (en) | 1987-11-20 | 1991-02-19 | Abbott Laboratories | Intermediates for producing quinolone-3-carboxylic acids |
US4649911A (en) * | 1983-09-08 | 1987-03-17 | Baylor College Of Medicine | Small particle aerosol generator for treatment of respiratory disease including the lungs |
GB8328808D0 (en) * | 1983-10-28 | 1983-11-30 | Riker Laboratories Inc | Inhalation responsive dispensers |
JPS60202822A (ja) | 1984-03-28 | 1985-10-14 | Dai Ichi Seiyaku Co Ltd | 抗ウイルス薬 |
US4624251A (en) | 1984-09-13 | 1986-11-25 | Riker Laboratories, Inc. | Apparatus for administering a nebulized substance |
US4648393A (en) * | 1984-11-02 | 1987-03-10 | Ackrad Laboratories, Inc. | Breath activated medication spray |
FR2575678B1 (fr) * | 1985-01-04 | 1988-06-03 | Saint Gobain Vitrage | Ejecteur pneumatique de poudre |
US4805811A (en) * | 1985-03-29 | 1989-02-21 | Aktiebolaget Draco | Dosage device |
DK170473B1 (da) * | 1985-06-20 | 1995-09-11 | Daiichi Seiyaku Co | S(-)-pyridobenzoxazinforbindelser |
AU591152B2 (en) | 1985-07-30 | 1989-11-30 | Glaxo Group Limited | Devices for administering medicaments to patients |
US4977154A (en) | 1985-12-12 | 1990-12-11 | Warner-Lambert Company | 5-amino and 5-hydroxy-6-fluoroquinolones as antibacterial agents |
US4809692A (en) * | 1986-01-31 | 1989-03-07 | Trudell Medical | Pediatric asthmatic medication inhaler |
IT1204826B (it) | 1986-03-04 | 1989-03-10 | Chiesi Farma Spa | Composizioni farmaceutiche per inalazione |
US4926852B1 (en) * | 1986-06-23 | 1995-05-23 | Univ Johns Hopkins | Medication delivery system phase one |
US4790305A (en) | 1986-06-23 | 1988-12-13 | The Johns Hopkins University | Medication delivery system |
JPS63188627A (ja) | 1987-01-31 | 1988-08-04 | Rooto Seiyaku Kk | 抗アレルギ−・抗炎症剤 |
DE3704907A1 (de) | 1987-02-17 | 1988-08-25 | Bayer Ag | Topisch anwendbare zubereitungen von gyrase-inhibitoren in kombination mit kortikosteroiden |
US5119806A (en) * | 1987-05-12 | 1992-06-09 | Glaxo Inc. | Inhalation device |
KR910000142B1 (ko) | 1987-05-29 | 1991-01-21 | 니혼 다바고 상교오 가부시기가이샤 | 담배용 필터 |
MX12213A (es) | 1987-07-09 | 1993-05-01 | Pfizer | Metodo de preparacion de dihidrato de azitromicina cristalino |
US4857311A (en) | 1987-07-31 | 1989-08-15 | Massachusetts Institute Of Technology | Polyanhydrides with improved hydrolytic degradation properties |
US4907538A (en) * | 1988-05-09 | 1990-03-13 | Little Suamico Products Inc. | Multiple bin cow feeder |
US4832015A (en) * | 1988-05-19 | 1989-05-23 | Trudell Medical | Pediatric asthmatic inhaler |
IT1217890B (it) | 1988-06-22 | 1990-03-30 | Chiesi Farma Spa | Dispositivo per l'inalazione di aerosol dosati |
FR2636716B1 (fr) * | 1988-09-21 | 1990-12-07 | Staubli Sa Ets | Dispositif pour l'accouplement des platines porte-elements des raccords multiples |
ES2051371T3 (es) | 1988-10-04 | 1994-06-16 | Univ Johns Hopkins | Inhalador de aerosoles. |
DK479189D0 (da) | 1989-01-06 | 1989-09-28 | Hans Gernot Schenk | Inhalator |
US5012803A (en) * | 1989-03-06 | 1991-05-07 | Trudell Medical | Modular medication inhaler |
US5012804A (en) * | 1989-03-06 | 1991-05-07 | Trudell Medical | Medication inhaler with adult mask |
GB8908647D0 (en) * | 1989-04-17 | 1989-06-01 | Glaxo Group Ltd | Device |
JPH05501505A (ja) | 1989-04-28 | 1993-03-25 | ライカー ラボラトリーズ,インコーポレイティド | 乾燥粉末吸入装置 |
US4955371A (en) | 1989-05-08 | 1990-09-11 | Transtech Scientific, Inc. | Disposable inhalation activated, aerosol device for pulmonary medicine |
IT1237118B (it) | 1989-10-27 | 1993-05-18 | Miat Spa | Inalatore multidose per farmaci in polvere. |
ES2102393T3 (es) | 1989-12-29 | 1997-08-01 | Abbott Lab | Complejos de acido quinolona carboxilico--ion metalico--acido. |
US5113855A (en) * | 1990-02-14 | 1992-05-19 | Newhouse Michael T | Powder inhaler |
US5192548A (en) | 1990-04-30 | 1993-03-09 | Riker Laboratoires, Inc. | Device |
GB9015077D0 (en) | 1990-07-09 | 1990-08-29 | Riker Laboratories Inc | Inhaler |
GB9015522D0 (en) | 1990-07-13 | 1990-08-29 | Braithwaite Philip W | Inhaler |
IT1243344B (it) | 1990-07-16 | 1994-06-10 | Promo Pack Sa | Inalatore plurimonodose per medicamenti in polvere |
US5060643A (en) | 1990-08-07 | 1991-10-29 | Tenax Corporation | Breath-activated inhalation device |
FR2665635A1 (fr) * | 1990-08-10 | 1992-02-14 | Merck Sharp & Dohme | Composition pharmaceutique fluide a base d'un complexe metallique et son procede de preparation. |
GB9026025D0 (en) | 1990-11-29 | 1991-01-16 | Boehringer Ingelheim Kg | Inhalation device |
US5258528A (en) | 1990-11-30 | 1993-11-02 | Warner-Lambert Company | Individual stereoisomers of pyrrolidine methanamines substituted on the ring nitrogen by a 1-phenylethyl group |
US5217004A (en) * | 1990-12-13 | 1993-06-08 | Tenax Corporation | Inhalation actuated dispensing apparatus |
US5040527A (en) | 1990-12-18 | 1991-08-20 | Healthscan Products Inc. | Metered dose inhalation unit with slide means |
US5404871A (en) * | 1991-03-05 | 1995-04-11 | Aradigm | Delivery of aerosol medications for inspiration |
US5164740A (en) | 1991-04-24 | 1992-11-17 | Yehuda Ivri | High frequency printing mechanism |
AU651882B2 (en) * | 1991-05-14 | 1994-08-04 | Visiomed Group Limited | Aerosol inhalation device |
HUT67449A (en) | 1991-06-10 | 1995-04-28 | Schering Corp | Aerosol formulations containing 1,1,1,2,3,3,3-heptafluoropropane |
DE69230613T2 (de) | 1991-07-02 | 2000-12-28 | Inhale Inc | Verfahren und vorrichtung zum abgeben von medikamenten in aerosolform |
IT1250691B (it) | 1991-07-22 | 1995-04-21 | Giancarlo Santus | Composizioni terapeutiche per somministrazione intranasale comprendenti ketorolac. |
DK0540775T3 (da) | 1991-11-07 | 1997-08-25 | Ritzau Pari Werk Gmbh Paul | Forstøver især til anvendelse i apparater til inhalationsterapi |
DE4140689B4 (de) | 1991-12-10 | 2007-11-22 | Boehringer Ingelheim Kg | Inhalationspulver und Verfahren zu ihrer Herstellung |
DE4142238A1 (de) | 1991-12-20 | 1993-06-24 | Boehringer Ingelheim Kg | Pulverinhalator mit pulvertraeger aus regelmaessigen mikrostrukturen |
CA2136835C (en) | 1992-05-29 | 2000-02-29 | Helmut Heide | Device for generating inhalable active substance particles |
US5785049A (en) * | 1994-09-21 | 1998-07-28 | Inhale Therapeutic Systems | Method and apparatus for dispersion of dry powder medicaments |
US5284133A (en) * | 1992-07-23 | 1994-02-08 | Armstrong Pharmaceuticals, Inc. | Inhalation device with a dose-timer, an actuator mechanism, and patient compliance monitoring means |
EG20543A (en) | 1992-10-30 | 1999-07-31 | Procter & Gamble | Process for preparing of novel antimicrobial -5- (n-heterosubstituted amino) quinolones |
NZ250105A (en) | 1992-11-09 | 1996-07-26 | Monaghan Canadian Ltd | Inhalator mask; one-way valve opens upon exhalation |
DE69323897T2 (de) | 1992-12-18 | 1999-11-04 | Schering Corp | Inhalator für pulverförmige medikamente |
US5558085A (en) | 1993-01-29 | 1996-09-24 | Aradigm Corporation | Intrapulmonary delivery of peptide drugs |
US5364838A (en) | 1993-01-29 | 1994-11-15 | Miris Medical Corporation | Method of administration of insulin |
US5934272A (en) | 1993-01-29 | 1999-08-10 | Aradigm Corporation | Device and method of creating aerosolized mist of respiratory drug |
US5709202A (en) * | 1993-05-21 | 1998-01-20 | Aradigm Corporation | Intrapulmonary delivery of aerosolized formulations |
US5532239A (en) | 1993-08-02 | 1996-07-02 | Assistance Publique - Hopitaux De Paris | Therapeutic application of fluoroquinolone derivatives |
US5688792A (en) | 1994-08-16 | 1997-11-18 | Pharmacia & Upjohn Company | Substituted oxazine and thiazine oxazolidinone antimicrobials |
MY115155A (en) | 1993-09-09 | 2003-04-30 | Upjohn Co | Substituted oxazine and thiazine oxazolidinone antimicrobials. |
US5388572A (en) * | 1993-10-26 | 1995-02-14 | Tenax Corporation (A Connecticut Corp.) | Dry powder medicament inhalator having an inhalation-activated piston to aerosolize dose and deliver same |
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 |
US5404781A (en) | 1994-06-09 | 1995-04-11 | Ko Shin Electric And Machinery Co., Ltd. | Anti-sway means for a saw web |
US5642730A (en) | 1994-06-17 | 1997-07-01 | Trudell Medical Limited | Catheter system for delivery of aerosolized medicine for use with pressurized propellant canister |
US5820873A (en) | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
US5508269A (en) * | 1994-10-19 | 1996-04-16 | Pathogenesis Corporation | Aminoglycoside formulation for aerosolization |
GB9501841D0 (en) | 1995-01-31 | 1995-03-22 | Co Ordinated Drug Dev | Improvements in and relating to carrier particles for use in dry powder inhalers |
EP0810853B1 (en) | 1995-02-24 | 2004-08-25 | Elan Pharma International Limited | Aerosols containing nanoparticle dispersions |
US6427682B1 (en) | 1995-04-05 | 2002-08-06 | Aerogen, Inc. | Methods and apparatus for aerosolizing a substance |
US5758637A (en) * | 1995-08-31 | 1998-06-02 | Aerogen, Inc. | Liquid dispensing apparatus and methods |
US5586550A (en) | 1995-08-31 | 1996-12-24 | Fluid Propulsion Technologies, Inc. | Apparatus and methods for the delivery of therapeutic liquids to the respiratory system |
US5921237A (en) | 1995-04-24 | 1999-07-13 | Dura Pharmaceuticals, Inc. | Dry powder inhaler |
US6672304B1 (en) * | 1995-06-08 | 2004-01-06 | Innovative Devices, Llc | Inhalation actuated device for use with metered dose inhalers (MDIs) |
NZ310990A (en) | 1995-06-21 | 2000-03-27 | Asta Medica Ag | Pharmaceutical powder cartridge, with an integrated metering slide, and inhaler therefor |
CA2176298C (en) * | 1995-06-27 | 2009-01-27 | Dennis D. Copeland | A single high dose fluoroquinolone treatment |
AUPN417395A0 (en) | 1995-07-14 | 1995-08-10 | Techbase Pty. Ltd. | An improved spacer |
JP5042447B2 (ja) | 1995-07-21 | 2012-10-03 | 第一三共株式会社 | 混合製剤 |
GB9515182D0 (en) | 1995-07-24 | 1995-09-20 | Co Ordinated Drug Dev | Improvements in and relating to powders for use in dry powder inhalers |
US6209538B1 (en) * | 1995-08-02 | 2001-04-03 | Robert A. Casper | Dry powder medicament inhalator having an inhalation-activated flow diverting means for triggering delivery of medicament |
SE9502799D0 (sv) | 1995-08-10 | 1995-08-10 | Astra Ab | Device in inhalers |
CN1104899C (zh) | 1995-12-21 | 2003-04-09 | 美国辉瑞有限公司 | 可注射喹诺酮制剂 |
US6026809A (en) * | 1996-01-25 | 2000-02-22 | Microdose Technologies, Inc. | Inhalation device |
US5694920A (en) | 1996-01-25 | 1997-12-09 | Abrams; Andrew L. | Inhalation device |
US5823179A (en) | 1996-02-13 | 1998-10-20 | 1263152 Ontario Inc. | Nebulizer apparatus and method |
US6083922A (en) | 1996-04-02 | 2000-07-04 | Pathogenesis, Corp. | Method and a tobramycin aerosol formulation for treatment prevention and containment of tuberculosis |
FR2747311B1 (fr) * | 1996-04-10 | 1998-08-14 | Pf Medicament | Inhalateur a poudre et a air comprime |
US6579854B1 (en) * | 1996-08-14 | 2003-06-17 | Vanderbilt University | Diagnosis and management of infection caused by chlamydia |
US6838552B1 (en) * | 1997-08-14 | 2005-01-04 | Vanderbilt University | Diagnosis and management of infection caused by Chlamydia |
US5906202A (en) * | 1996-11-21 | 1999-05-25 | Aradigm Corporation | Device and method for directing aerosolized mist to a specific area of the respiratory tract |
CA2227314A1 (en) | 1997-01-24 | 1998-07-24 | Hoechst Aktiengesellschaft | Preparation of concealed taste preparations of antibacterially active quinolone derivatives |
US6349719B2 (en) * | 1997-02-24 | 2002-02-26 | Aradigm Corporation | Formulation and devices for monitoring the efficacy of the delivery of aerosols |
US6006747A (en) | 1997-03-20 | 1999-12-28 | Dura Pharmaceuticals, Inc. | Dry powder inhaler |
US6406880B1 (en) * | 1997-05-02 | 2002-06-18 | Integrated Research Technology, Llc | Betaines as adjuvants to susceptibility testing and antimicrobial therapy |
US6884784B1 (en) * | 1997-05-06 | 2005-04-26 | Vanderbilt University | Diagnosis and management of infection caused by chlamydia |
US6890526B2 (en) * | 1997-05-06 | 2005-05-10 | Vanderbilt University | Methods and reagents for the treatment of multiple sclerosis |
US6664239B2 (en) | 1997-05-06 | 2003-12-16 | Vanderbilt University | Diagnosis and management of infection caused by Chlamydia |
US6756369B2 (en) * | 1997-05-06 | 2004-06-29 | Vanderbilt University | Diagnosis and management of infection caused by Chlamydia |
US5855564A (en) | 1997-08-20 | 1999-01-05 | Aradigm Corporation | Aerosol extrusion mechanism |
US20010044584A1 (en) * | 1997-08-28 | 2001-11-22 | Kensey Kenneth R. | In vivo delivery methods and compositions |
US6293279B1 (en) | 1997-09-26 | 2001-09-25 | Trudell Medical International | Aerosol medication delivery apparatus and system |
US20030082107A1 (en) | 1997-10-01 | 2003-05-01 | Dugger Harry A. | Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer |
KR20010024453A (ko) | 1997-10-08 | 2001-03-26 | 더글라스이.리디치 | 에어로졸 투여용 투약 형태 |
US6003512A (en) | 1997-11-13 | 1999-12-21 | Lovelace Respiratory Research Institute | Dust gun-aerosol generator and generation |
EP1129741B1 (en) * | 1997-11-19 | 2006-04-12 | Microflow Engineering SA | Spray device for an inhaler |
ID21415A (id) | 1997-12-05 | 1999-06-10 | Upjohn Co | Senyawa-senyawa antibiotik magnesium quinolon |
US6192876B1 (en) * | 1997-12-12 | 2001-02-27 | Astra Aktiebolag | Inhalation apparatus and method |
US6223746B1 (en) * | 1998-02-12 | 2001-05-01 | Iep Pharmaceutical Devices Inc. | Metered dose inhaler pump |
US6026807A (en) * | 1998-02-27 | 2000-02-22 | Diemolding Corporation | Metered dose inhaler cloud chamber |
GB9810299D0 (en) | 1998-05-15 | 1998-07-15 | Glaxo Group Ltd | Use of nitric oxide synthase inhibitors |
US6257233B1 (en) | 1998-06-04 | 2001-07-10 | Inhale Therapeutic Systems | Dry powder dispersing apparatus and methods for their use |
ATE283033T1 (de) | 1998-07-24 | 2004-12-15 | Jago Res Ag | Medizinische aerosolformulierungen |
BRPI9906735B8 (pt) | 1998-08-21 | 2021-05-25 | Kyorin Seiyaku Kk | 'composição farmacêutica líquida aquosa e método para prevenção de precipitações de cristais e para prevenção da coloração de gatifloxacina.' |
DK1115417T3 (da) | 1998-09-25 | 2006-07-31 | Cubist Pharm Inc | Anvendelse af daptomycin |
US6395746B1 (en) | 1998-09-30 | 2002-05-28 | Alcon Manufacturing, Ltd. | Methods of treating ophthalmic, otic and nasal infections and attendant inflammation |
GB2343122B (en) * | 1998-10-26 | 2003-01-08 | Medic Aid Ltd | Improvements in and relating to nebulisers |
US6070575A (en) * | 1998-11-16 | 2000-06-06 | Aradigm Corporation | Aerosol-forming porous membrane with certain pore structure |
US6584971B1 (en) | 1999-01-04 | 2003-07-01 | Medic-Aid Limited | Drug delivery apparatus |
US6350199B1 (en) * | 1999-03-16 | 2002-02-26 | International Game Technology | Interactive gaming machine and method with customized game screen presentation |
US7919119B2 (en) | 1999-05-27 | 2011-04-05 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
US6338443B1 (en) * | 1999-06-18 | 2002-01-15 | Mercury Enterprises, Inc. | High efficiency medical nebulizer |
CA2282066C (en) | 1999-06-29 | 2010-09-07 | Smithkline Beecham Corporation | Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria |
US6576224B1 (en) | 1999-07-06 | 2003-06-10 | Sinuspharma, Inc. | Aerosolized anti-infectives, anti-inflammatories, and decongestants for the treatment of sinusitis |
US20020061281A1 (en) * | 1999-07-06 | 2002-05-23 | Osbakken Robert S. | Aerosolized anti-infectives, anti-inflammatories, and decongestants for the treatment of sinusitis |
US6586008B1 (en) | 1999-08-25 | 2003-07-01 | Advanced Inhalation Research, Inc. | Use of simple amino acids to form porous particles during spray drying |
DE60044070D1 (de) | 1999-10-29 | 2010-05-06 | Novartis Ag | Trockenpulverzusammensetzungen mit verbesserter Dispersität |
DK1225898T3 (da) | 1999-11-01 | 2003-09-15 | Alcon Inc | Farmaceutisk præparat indeholdende et fluorquinolonantibiotisk lægemiddel og xanthangummi |
US6294178B1 (en) | 1999-11-01 | 2001-09-25 | Robert E. Weinstein | Method and device for coordinating topical and oral sinusitis treatments |
US6962151B1 (en) | 1999-11-05 | 2005-11-08 | Pari GmbH Spezialisten für effektive Inhalation | Inhalation nebulizer |
US20010049366A1 (en) | 2000-02-09 | 2001-12-06 | Alcon Universal Ltd. | Topical solution formulations containing an antibiotic and a corticosteroid |
US6667057B2 (en) * | 2000-02-24 | 2003-12-23 | Advancis Pharmaceutical Corp. | Levofloxacin antibiotic product, use and formulation thereof |
US6669948B2 (en) | 2000-02-24 | 2003-12-30 | Advancis Pharmaceutical Corp. | Antibiotic product, use and formulation thereof |
US6544555B2 (en) * | 2000-02-24 | 2003-04-08 | Advancis Pharmaceutical Corp. | Antibiotic product, use and formulation thereof |
US6663891B2 (en) | 2000-02-24 | 2003-12-16 | Advancis Pharmaceutical Corp. | Erythromyacin antibiotic product, use and formulation thereof |
US6663890B2 (en) | 2000-02-24 | 2003-12-16 | Advancis Pharmaceutical Corp. | Metronidazole antibiotic product, use and formulation thereof |
US6730320B2 (en) * | 2000-02-24 | 2004-05-04 | Advancis Pharmaceutical Corp. | Tetracycline antibiotic product, use and formulation thereof |
US6667042B2 (en) | 2000-02-24 | 2003-12-23 | Advancis Pharmaceutical Corp. | Fluroquinilone antibiotic product, use and formulation thereof |
DE60114393T2 (de) * | 2000-04-11 | 2006-04-27 | Trudell Medical International, London | Aerosolspender mit einer möglichkeit für positiven ausatemdruck |
US20020076437A1 (en) | 2000-04-12 | 2002-06-20 | Sanjeev Kothari | Flashmelt oral dosage formulation |
US6608078B2 (en) | 2000-05-08 | 2003-08-19 | Wockhardt Limited | Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment |
US6716819B2 (en) * | 2000-05-19 | 2004-04-06 | University Of Iowa Research Foundation | Use of xylitol to reduce ionic strength and activate endogenous antimicrobials for prevention and treatment of infections |
PE20020044A1 (es) | 2000-06-16 | 2002-01-30 | Upjohn Co | Tiazina oxazolidinona |
US6492328B2 (en) | 2000-06-28 | 2002-12-10 | The University Of Iowa Research Foundation | Novispirins: antimicrobial peptides |
WO2002006301A2 (en) | 2000-06-30 | 2002-01-24 | University Of Cincinnati | Peptides with antioxidant and antimicrobial properties |
AU2001282988B2 (en) * | 2000-07-26 | 2006-01-05 | Atopic Pty Ltd | Methods for treating atopic disorders |
EP1313708A1 (en) | 2000-08-29 | 2003-05-28 | Chiron Corporation | Quinoline antibacterial compounds and methods of use thereof |
TWI290053B (en) | 2000-09-19 | 2007-11-21 | Daiichi Seiyaku Co | Medicinal composition for preventing the generation of a disagreeable taste |
US6298656B1 (en) | 2000-09-29 | 2001-10-09 | Siemens Westinghouse Power Corporation | Compressed air steam generator for cooling combustion turbine transition section |
US6601581B1 (en) | 2000-11-01 | 2003-08-05 | Advanced Medical Applications, Inc. | Method and device for ultrasound drug delivery |
EP1349853B1 (en) * | 2000-12-21 | 2006-03-08 | Pharmacia & Upjohn Company LLC | Antimicrobial quinolone derivatives and use of the same to treat bacterial infections |
US6626173B2 (en) | 2001-01-08 | 2003-09-30 | Iep Pharmaceutical Devices Inc. | Dry powder inhaler |
JP2004535370A (ja) | 2001-03-05 | 2004-11-25 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | 味をマスクした液体製薬学的組成物 |
US6523536B2 (en) * | 2001-03-12 | 2003-02-25 | Birdsong Medical Devices, Inc. | Dual-canister inhaler having a spacer and easy to operate lever mechanism |
US6878713B2 (en) * | 2001-04-25 | 2005-04-12 | Wockhardt Limited | Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments |
US6589955B2 (en) * | 2001-06-20 | 2003-07-08 | Bristol-Myers Squibb Company | Pediatric formulation of gatifloxacin |
US6681768B2 (en) * | 2001-06-22 | 2004-01-27 | Sofotec Gmbh & Co. Kg | Powder formulation disintegrating system and method for dry powder inhalers |
US20030138403A1 (en) | 2001-06-29 | 2003-07-24 | Maxygen Aps | Interferon formulations |
ES2222294T3 (es) * | 2001-07-02 | 2005-02-01 | Chiesi Farmaceutici S.P.A. | Formulacion optimizada de tobramicina para administracion en forma de aerosol. |
CA2464250C (en) | 2001-10-24 | 2008-08-05 | Frank-Christophe Lintz | Kit for the preparation of a pharmaceutical composition |
US20040014750A1 (en) * | 2001-12-13 | 2004-01-22 | Michaelis Arthur F. | Metal complexes and formulations of rifamycin analogues and uses thereof |
US20030143265A1 (en) | 2001-12-19 | 2003-07-31 | Seiichi Araki | Method for treatment of sepsis |
US20030171340A1 (en) | 2002-02-07 | 2003-09-11 | Jenefir Isbister | Methods of disease treatment using metal-complexed tetracycline antibiotics |
EP1490027A4 (en) | 2002-03-05 | 2010-11-10 | Transave Inc | METHODS OF TRAPPING BIOACTIVE AGENT IN A LIPOSOME OR LIPID COMPLEX |
WO2003075935A1 (fr) | 2002-03-11 | 2003-09-18 | Eisai Co., Ltd. | Medicaments contenant des composes du type riboflavine |
JP4290381B2 (ja) | 2002-04-11 | 2009-07-01 | 学校法人 聖マリアンナ医科大学 | ピリドンカルボン酸化合物含有エマルション |
US7607436B2 (en) | 2002-05-06 | 2009-10-27 | The Research Foundation Of State University Of New York | Methods, devices and formulations for targeted endobronchial therapy |
US20040025876A1 (en) | 2002-05-07 | 2004-02-12 | Danforth Miller | Capsules for dry powder inhalers and methods of making and using same |
US7423153B2 (en) * | 2002-05-10 | 2008-09-09 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of gatifloxacin |
US20040045546A1 (en) * | 2002-09-05 | 2004-03-11 | Peirce Management, Llc | Pharmaceutical delivery system for oral inhalation through nebulization consisting of inert substrate impregnated with substance (S) to be solubilized or suspended prior to use |
US20040152701A1 (en) | 2002-12-02 | 2004-08-05 | Dr. Reddy's Laboratories Limited | Novel anhydrous crystalline form of Levofloxacin and process for preparation there of |
WO2004055025A1 (en) | 2002-12-16 | 2004-07-01 | Ranbaxy Laboratories Limited | Pure levofloxacin hemihydrate and processes for preparation thereof |
EP1589943A2 (en) * | 2003-01-09 | 2005-11-02 | Arizeke Pharmaceuticals, Inc. | Methods of treating lung diseases |
NZ541681A (en) | 2003-02-10 | 2009-02-28 | Bayer Healthcare Ag | Treatment of bacterial diseases of the respiratory organs by locally applying ciprofloxacin and its salts |
US20060258677A1 (en) | 2003-02-15 | 2006-11-16 | Teva Pharmaceutical Industries Ltd. | Novel crystalline forms of gatifloxacin and processes for preparation |
DK1459739T3 (da) | 2003-03-19 | 2008-05-19 | Jordanian Pharmaceutical Mfg | Ikke-hydroskopiske farmaceutiske sammensætninger indeholdende ikke-hydratiserede quinolin-carboxylsyrer |
DE10318235A1 (de) | 2003-04-22 | 2004-11-11 | Clariant Gmbh | Leicht dispergierbare Pigmente mit schneller Farbstärkeentwicklung |
US20070248693A1 (en) | 2003-08-02 | 2007-10-25 | Elizabeth Mazzio | Nutraceutical composition and method of use for treatment / prevention of cancer |
JP2007504144A (ja) * | 2003-08-26 | 2007-03-01 | ザ リージェンツ オブ ザ ユニバーシティー オブ コロラド ア ボディー コーポレイト | セリンプロテアーゼ活性阻害因子、ならびに細菌感染の治療法および組成物におけるその使用方法 |
SE0302665D0 (sv) | 2003-10-07 | 2003-10-07 | Astrazeneca Ab | Novel Process |
CN1312076C (zh) | 2003-10-14 | 2007-04-25 | 长沙理工大学 | 应用铬铁合金为原料生产的陶瓷玻璃色料及其生产方法 |
US20070071686A1 (en) * | 2003-10-15 | 2007-03-29 | Pari Gmbh | Liquid preparation containing tobramycin |
JP4933262B2 (ja) | 2003-11-17 | 2012-05-16 | ネクター セラピューティクス | 人工呼吸器循環路へのエアロゾル導入 |
US7452524B2 (en) | 2004-01-27 | 2008-11-18 | Gilead Sciences, Inc. | Method for improvement of tolerance for therapeutically effective agents delivered by inhalation |
JP2008500965A (ja) | 2004-03-17 | 2008-01-17 | エムペックス・ファーマシューティカルズ・インコーポレーテッド | 細菌の排出ポンプ阻害剤の使用および投与 |
US7148404B2 (en) | 2004-05-04 | 2006-12-12 | Novozymes A/S | Antimicrobial polypeptides |
WO2005113579A1 (en) * | 2004-05-21 | 2005-12-01 | Mpex Pharmaceuticals, Inc. | Bacterial efflux pump inhibitors and methods of treating bacterial infections |
US7632869B2 (en) | 2004-05-24 | 2009-12-15 | Bausch & Lomb Incorporated | Antimicrobial compositions and uses thereof |
JP2008503586A (ja) * | 2004-06-21 | 2008-02-07 | ネクター セラピューティクス | アンフォテリシンbを含む組成物、方法、およびシステム |
BRPI0513455A (pt) | 2004-07-22 | 2008-05-06 | Pfizer Prod Inc | formulação para mascaramento de sabor compreendendo o fármaco em uma forma de dissolução retardada e/ou ciclodextrina em uma forma de dissolução melhorada |
WO2006033713A2 (en) | 2004-08-09 | 2006-03-30 | Chiron Corporation | Methods for ciprofloxacin inhalation |
US7388077B2 (en) | 2004-11-12 | 2008-06-17 | Novozymes A/S | Polypeptides having antimicrobial activity and polynucleotides encoding the same |
WO2006079021A2 (en) * | 2005-01-20 | 2006-07-27 | Sirtris Pharmaceuticals, Inc. | Use of sirtuin-activating compounds for treating flushing and drug induced weight gain |
AU2006206359B2 (en) | 2005-01-21 | 2011-03-31 | Allergan Pharmaceuticals International Limited | A tetracycline metal complex in a solid dosage form |
EP1862184A4 (en) | 2005-03-24 | 2012-12-19 | Daiichi Sankyo Co Ltd | PHARMACEUTICAL COMPOSITION |
EP1871910A4 (en) | 2005-04-05 | 2009-07-29 | Scripps Research Inst | COMPOSITIONS AND METHODS FOR IMPROVING DRUG SENSITIVITY AND TREATING DRUG-RESISTANT INFECTIONS AND DISEASES |
US8524734B2 (en) | 2005-05-18 | 2013-09-03 | Mpex Pharmaceuticals, Inc. | Aerosolized fluoroquinolones and uses thereof |
US7838532B2 (en) * | 2005-05-18 | 2010-11-23 | Mpex Pharmaceuticals, Inc. | Aerosolized fluoroquinolones and uses thereof |
LT1901749T (lt) | 2005-05-18 | 2016-10-25 | Raptor Pharmaceuticals Inc. | Aerozoliniai fluorchinolinai ir jų naudojimas |
CN101212990A (zh) * | 2005-07-01 | 2008-07-02 | 金文申有限公司 | 包含网状复合材料的医疗器械 |
WO2007070613A2 (en) | 2005-12-14 | 2007-06-21 | Activbiotics, Incorporated | Rifamycin analogs and uses thereof |
WO2007085057A1 (en) | 2006-01-25 | 2007-08-02 | The Council Of The Queensland Institute Of Medical Research | A medical protocol |
WO2007090123A2 (en) | 2006-01-30 | 2007-08-09 | University Of Chicago | Mgra is a redox regulator of antibiotic sensitivity and virulence |
EP1991201B1 (en) | 2006-02-10 | 2018-03-28 | PARI Pharma GmbH | Nebulised antibiotics for inhalation therapy |
WO2007095187A2 (en) | 2006-02-13 | 2007-08-23 | Trustees Of Boston University | Compositions and methods for antibiotic potentiation and drug discovery |
US20070197548A1 (en) | 2006-02-17 | 2007-08-23 | Murthy Yerramilli V S | Fluoroquinolone compositions |
WO2008000418A2 (en) | 2006-06-27 | 2008-01-03 | Sandoz Ag | New method for salt preparation |
WO2008025560A1 (en) | 2006-09-01 | 2008-03-06 | Pari Pharma Gmbh | Methods for taste masking of nebulised compositions for nasal and pulmonary inhalation therapy |
US20080276935A1 (en) | 2006-11-20 | 2008-11-13 | Lixiao Wang | Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs |
US8080394B2 (en) | 2007-04-27 | 2011-12-20 | Brigham And Women's Hospital | Method for determining predisposition to pulmonary infection |
GB0719248D0 (en) | 2007-10-03 | 2007-11-14 | Generics Uk Ltd | Compounds and methods for pharmaceutical use |
US20090227018A1 (en) | 2007-10-25 | 2009-09-10 | Revalesio Corporation | Compositions and methods for modulating cellular membrane-mediated intracellular signal transduction |
US20090197212A1 (en) | 2008-02-04 | 2009-08-06 | Maxitrol Company | Premix Burner Control System and Method |
EP2285345A1 (en) | 2008-05-15 | 2011-02-23 | Novartis AG | Pulmonary delivery of a fluoroquinolone |
JP2012505223A (ja) | 2008-10-07 | 2012-03-01 | エムペックス・ファーマシューティカルズ・インコーポレーテッド | 薬物動態の改善のためのエアゾールフルオロキノロン配合物 |
JP2012505222A (ja) * | 2008-10-07 | 2012-03-01 | エムペックス・ファーマシューティカルズ・インコーポレーテッド | 肺炎症を低減するためのレボフロキサシンの吸入 |
HUE046595T2 (hu) | 2009-04-24 | 2020-03-30 | Horizon Orphan Llc | Eljárások bakteriális tüdõfertõzés kezelésére fluorokinolonok alkalmazásával |
EP2467138A4 (en) * | 2009-08-19 | 2013-11-06 | Mpex Pharmaceuticals Inc | USE OF AEROSOLIZED ANTIBIOTICS FOR THE TREATMENT OF CHRONIC OBSTRUCTIVE LUNG DISEASE |
EP2467715A4 (en) * | 2009-08-19 | 2013-01-16 | Mpex Pharmaceuticals Inc | AEROSOL AT RIBOFLAVINBASIS AND ITS USE AS PLACEBO IN TRYING |
AU2010289326B2 (en) | 2009-09-04 | 2015-09-24 | Horizon Therapeutics U.S. Holding Llc | Use of aerosolized levofloxacin for treating cystic fibrosis |
WO2014032184A1 (en) | 2012-08-31 | 2014-03-06 | Alectos Therapeutics Inc. | Glycosidase inhibitors and uses thereof |
CN107848970B (zh) | 2015-07-30 | 2021-07-06 | 地平线孤儿病有限责任公司 | 岩藻糖苷酶抑制剂 |
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