JP2020055877A - 非結核性抗酸菌肺感染症を治療するための方法 - Google Patents
非結核性抗酸菌肺感染症を治療するための方法 Download PDFInfo
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Abstract
Description
本願は、それぞれの開示の全体が、あらゆる目的で、参照により組み込まれる、2014年5月15日に出願された、米国仮出願第61/993,439号;2014年8月26日に出願された同第62/042,126号;2014年9月9日に出願された同第62/048,068号;および2014年9月26日に出願された同第62/056、296号からの優先権を主張する。
[00130] NTM−LDの増加する有病率は、公衆衛生上の問題であり、特に嚢胞性線維症患者におけるその管理は、多剤レジメンの長期使用、薬物毒性および不十分な奏効率によって複雑化する。LAI(本明細書中で「Arikayce(商標)」または「ARIKAYCE(商標)」とも称される)は、不応性NTM肺疾患を有する患者の治療のために開発中のアミカシンの徐放性脂質組成物である。この試験は、北米の19の拠点において行った、無作為化二重盲検(DB)試験において、これらの患者におけるLAIの有効性、安全性および耐容性を評価した。図1は、試験デザインを示すフローチャートであり、図2は、この試験のための患者分布を示す。
[00148] LAI(本明細書中で「Arikayce(商標)」または「ARIKAYCE(商標)」とも称される)は、不応性のNTM肺疾患を有する患者の治療のために開発中のアミカシンの徐放性脂質組成物である。この試験において、LAIの有効性、安全性および耐容性を、M.avium complex(MAC)肺感染症を有する非嚢胞性線維症患者において評価する。図9は、試験デザインを示すフローチャートである。
Claims (89)
- 治療または予防を必要とする患者における非結核性抗酸菌(NTM)肺感染症を治療するまたはそれに対する予防を提供するための方法であって、
複数のリポソーム中に封入されたアミノグリコシドまたはその薬学的に許容される塩を含む医薬組成物を、投与期間の間、患者の肺に投与することを含み、前記複数のリポソームの脂質成分は1つまたは複数の電気的に中性の脂質から成り、
前記患者の肺に投与することは、医薬組成物をエアロゾル化して、遊離アミノグリコシドおよびリポソーム複合体化アミノグリコシドの混合物を含むエアロゾル化された医薬組成物を供すること、およびネブライザーを介して患者の肺にエアロゾル化された医薬組成物を投与することを含み、
前記投与期間の間または投与期間の後、患者は、抗酸菌培養の完全な半定量的尺度におけるベースラインからの変化および/または投与期間の間もしくはその後におけるNTM培養の陰性転化を経験する、方法。 - 治療または予防を必要とする患者における非結核性抗酸菌(NTM)肺感染症を治療するまたはそれに対する予防を提供するための方法であって、
複数のリポソーム中に封入されたアミノグリコシドまたはその薬学的に許容される塩を含む医薬組成物を、投与期間の間、患者の肺に投与することを含み、前記複数のリポソームの脂質成分は、1つまたは複数の電気的に中性の脂質から成り、
前記患者の肺に投与することは、医薬組成物をエアロゾル化して、遊離アミノグリコシドおよびリポソーム複合体化アミノグリコシドの混合物を含むエアロゾル化された医薬組成物を供すること、およびネブライザーを介して患者の肺にエアロゾル化された医薬組成物を投与することを含み、
前記投与期間の間または投与期間の後、患者は、治療方法を受ける前に患者が歩いたメートル数に比べて増加した、6分間歩行試験(6MWT)において歩いたメートル数を示す、方法。 - 治療または予防を必要とする患者における非結核性抗酸菌(NTM)肺感染症を治療するまたはそれに対する予防を提供するための方法であって、
複数のリポソーム中に封入されたアミノグリコシドまたはその薬学的に許容される塩を含む医薬組成物を、投与期間の間、患者の肺に投与することを含み、前記複数のリポソームの脂質成分は、1つまたは複数の電気的に中性の脂質から成り、
前記患者の肺に投与することは、医薬組成物をエアロゾル化して、遊離アミノグリコシドおよびリポソーム複合体化アミノグリコシドの混合物を含むエアロゾル化された医薬組成物を供すること、およびネブライザーを介して患者の肺にエアロゾル化された医薬組成物を投与することを含み、
前記投与期間の間または投与期間の後、患者は、NTM肺感染症のための非リポソームアミノグリコシド治療に供された患者に比べてより多い、6MWTにおいて歩いたメートル数を示す、方法。 - 治療または予防を必要とする患者における非結核性抗酸菌(NTM)肺感染症を治療するまたはそれに対する予防を提供するための方法であって、
複数のリポソーム中に封入されたアミノグリコシドまたはその薬学的に許容される塩を含む医薬組成物を、投与期間の間、患者の肺に投与することを含み、前記複数のリポソームの脂質成分は、1つまたは複数の電気的に中性の脂質から成り、
前記患者の肺に投与することは、医薬組成物をエアロゾル化して、遊離アミノグリコシドおよびリポソーム複合体化アミノグリコシドの混合物を含むエアロゾル化された医薬組成物を供すること、およびネブライザーを介して患者の肺にエアロゾル化された医薬組成物を投与することを含み、
患者は、投与期間終了後少なくとも15日間、治療前の患者のFEV1に比べてFEV1の改善を経験する、方法。 - 前記アミノグリコシドまたはその薬学的に許容される塩が、アミカシン、アプラマイシン、アルベカシン、アストロマイシン、ベカナマイシン、ボホルマイシン、ブルラマイシン、カプレオマイシン、ジベカシン、ダクチマイシン、エチミシン、フラミセチン、ゲンタマイシン、H107、ハイグロマイシン、ハイグロマイシンB、イノサマイシン、K−4619、イセパマイシン、KA−5685、カナマイシン、ネオマイシン、ネチルマイシン、パロモマイシン、プラゾマイシン、リボスタマイシン、シソマイシン、ロドストレプトマイシン、ソルビスチン、スペクチノマイシン、スポラリシン、ストレプトマイシン、トブラマイシン、ベルダマイシン、ベルチルマイシン、薬学的に許容されるそれらの塩、またはそれらの組み合わせである、請求項1〜4のいずれか一項に記載の方法。
- 前記アミノグリコシドまたはその薬学的に許容される塩が、アミカシンである、請求項1〜4のいずれか一項に記載の方法。
- 前記アミノグリコシドまたはその薬学的に許容される塩が、アミカシン硫酸塩である、請求項1〜4のいずれか一項に記載の方法。
- 前記複数のリポソームが、一枚膜ベシクル、多重膜ベシクルまたはそれらの組み合わせを含む、請求項1〜7のいずれか一項に記載の方法。
- 前記電気的に中性の脂質が、電気的に中性のリン脂質または電気的に中性のリン脂質、およびステロールを含む、請求項1〜8のいずれか一項に記載の方法。
- 前記電気的に中性の脂質が、ホスファチジルコリンおよびステロールを含む、請求項1〜9のいずれか一項に記載の方法。
- 前記電気的に中性の脂質が、ジパルミトイルホスファチジルコリン(DPPC)およびステロールを含む、請求項1〜10のいずれか一項に記載の方法。
- 前記電気的に中性の脂質が、DPPCおよびコレステロールを含む、請求項1〜10のいずれか一項に記載の方法。
- 前記アミノグリコシドがアミカシンであり、前記電気的に中性の脂質がDPPCおよびコレステロールを含み、前記リポソームが一枚膜ベシクル、多重膜ベシクルまたはそれらの混合物を含む、請求項1〜12のいずれか一項に記載の方法。
- 患者に投与される医薬組成物の体積が、約8mL〜約10mLである、請求項1〜13のいずれか一項に記載の方法。
- 前記医薬組成物が、アミノグリコシドもしくはその薬学的に許容される塩約500mg〜約650mg、またはアミノグリコシドもしくはその薬学的に許容される塩約550mg〜約625mg、またはアミノグリコシドもしくはその薬学的に許容される塩約550mg〜約600mgを含む、請求項1〜14のいずれか一項に記載の方法。
- 前記医薬組成物が水性分散液である、請求項1〜15のいずれか一項に記載の方法。
- 前記医薬組成物が、アミカシンまたはその薬学的に許容される塩約70〜約75mg/mL;DPPC約32〜約35mg/mL;およびコレステロール約16〜約17mg/mLを含む、請求項1〜16のいずれか一項に記載の方法。
- 前記医薬組成物が、約8mLの体積を有する、請求項1〜17のいずれか一項に記載の方法。
- 前記エアロゾル化された医薬組成物が、投与期間の間、単一の投薬セッションにおいて1日1回投与される、請求項1〜18のいずれか一項に記載の方法。
- 単一の投薬セッションの間、前記エアロゾル化された医薬組成物が、約15分未満、約14分未満、約13分未満、約12分未満または約11分未満で投与される、請求項1〜19のいずれか一項に記載の方法。
- 単一の投薬セッションの間、前記エアロゾル化された医薬組成物が、約10分〜約14分、約10分〜約13分、約10分〜約12分、約10分〜約11分、約11分〜約15分、約12分〜約15分、約13分〜約15分または約14分〜約15分で投与される、請求項1〜20のいずれか一項に記載の方法。
- 前記エアロゾル化された医薬組成物の約25%〜約35%が、患者の肺の気管支および肺胞領域に沈着する、請求項1〜21のいずれか一項に記載の方法。
- 前記治療または予防を必要とする患者が、嚢胞性線維症を有する、請求項1〜22のいずれか一項に記載の方法。
- 前記治療または予防を必要とする患者が、気管支拡張症を有する、請求項1〜23のいずれか一項に記載の方法。
- 前記治療または予防を必要とする患者が、喫煙者であるかまたは喫煙の前歴を有する、請求項1〜24のいずれか一項に記載の方法。
- 前記治療または予防を必要とする患者が、慢性閉塞性肺疾患(COPD)を有する、請求項1〜25のいずれか一項に記載の方法。
- 前記治療または予防を必要とする患者が、喘息を有する、請求項1〜26のいずれか一項に記載の方法。
- 前記治療または予防を必要とする患者が、先にNTM治療法に対して非反応性であった、請求項1〜27のいずれか一項に記載の方法。
- 前記治療または予防を必要とする患者が、線毛機能不全症患者である、請求項1〜28のいずれか一項に記載の方法。
- 前記治療または予防を必要とする患者が、NTM肺感染症に加えて、糖尿病、僧帽弁障害、急性気管支炎、肺高血圧症、肺炎、喘息、気管癌、気管支癌、肺癌、嚢胞性線維症、肺線維症、咽頭異常、気管異常、気管支異常、アスペルギルス症、HIVまたは気管支拡張症から選ばれる併発状態を有する、請求項1〜29のいずれか一項に記載の方法。
- 僧帽弁障害が、僧帽弁逸脱症である、請求項30に記載の方法。
- NTM肺感染症が、M.avium感染症である、請求項1〜31のいずれか一項に記載の方法。
- M.avium感染症が、Mycobacterium avium subsp.hominissuis感染症である、請求項32に記載の方法。
- NTM肺感染症が、Mycobacterim abscessus感染症である、請求項1〜31のいずれか一項に記載の方法。
- NTM肺感染症が、Mycobacterium avium complex (M. aviumおよびM. intracellulare)である、請求項1〜31のいずれか一項に記載の方法。
- NTM肺感染症が、M.avium、M.avium subsp.hominissuis(MAH)、M.abscessus、M.chelonae、M.bolletii、M.kansasii、M.ulcerans、M.avium、M.avium complex(MAC)(M. aviumおよびM. intracellulare)、M.conspicuum、M.kansasii、M.peregrinum、M.immunogenum、M.xenopi、M.marinum、M.malmoense、M.marinum、M.mucogenicum、M.nonchromogenicum、M.scrofulaceum、M.simiae、M.smegmatis、M.szulgai、M.terrae、M.terrae complex、M.haemophilum、M.genavense、M.asiaticum、M.shimoidei、M.gordonae、M.nonchromogenicum、M.triplex、M.lentiflavum、M.celatum、M.fortuitum、M.fortuitum complex(M. fortuitumおよびM. chelonae)またはそれらの組み合わせである、請求項1〜31のいずれか一項に記載の方法。
- NTM肺感染症が、過敏性肺疾患に類似した症状を有するNTM肺感染症である、請求項1〜36のいずれか一項に記載の方法。
- NTM肺感染症が、マクロライド耐性NTM肺感染症である、請求項1〜36のいずれか一項に記載の方法。
- 前記治療または予防を必要とする患者に、1つまたは複数の追加の治療剤を投与することをさらに含む、請求項1〜38のいずれか一項に記載の方法。
- 前記1つまたは複数の追加の治療剤が、マクロライド系抗生物質である、請求項39に記載の方法。
- 前記マクロライド系抗生物質が、アジスロマイシン、クラリスロマイシン、エリスロマイシン、カルボマイシンA、ジョサマイシン、キタマイシン、ミデカマイシン、オレアンドマイシン、ソリスロマイシン、スピラマイシン、トロレアンドマイシン、タイロシン、ロキシスロマイシン、またはそれらの組み合わせである、請求項40に記載の方法。
- 前記マクロライド系抗生物質が、アジスロマイシンである、請求項40に記載の方法。
- 前記マクロライド系抗生物質が、クラリスロマイシンである、請求項40に記載の方法。
- 前記マクロライド系抗生物質が、エリスロマイシンである、請求項40に記載の方法。
- 前記マクロライド系抗生物質が経口投与される、請求項40〜44のいずれか一項に記載の方法。
- 前記1つまたは複数の追加の治療剤が、リファマイシンである、請求項39に記載の方法。
- リファマイシンが、リファンピンである、請求項46に記載の方法。
- リファマイシンが、リファブチン、リファペンチン、リファキシミンまたはそれらの組み合わせである、請求項46に記載の方法。
- 前記1つまたは複数の追加の治療剤が、キノロンである、請求項39に記載の方法。
- キノロンが、フルオロキノロンである、請求項49に記載の方法。
- 前記1つまたは複数の追加の治療剤が、第2のアミノグリコシドである、請求項39に記載の方法。
- 前記第2のアミノグリコシドが、アミカシン、アプラマイシン、アルベカシン、アストロマイシン、ベカナマイシン、ボホルマイシン、ブルラマイシン、カプレオマイシン、ジベカシン、ダクチマイシン、エチミシン、フラミセチン、ゲンタマイシン、H107、ハイグロマイシン、ハイグロマイシンB、イノサマイシン、K−4619、イセパマイシン、KA−5685、カナマイシン、ネオマイシン、ネチルマイシン、パロモマイシン、プラゾマイシン、リボスタマイシン、シソマイシン、ロドストレプトマイシン、ソルビスチン、スペクチノマイシン、スポラリシン、ストレプトマイシン、トブラマイシン、ベルダマイシン、ベルチルマイシン、薬学的に許容されるそれらの塩、またはそれらの組み合わせである、請求項51に記載の方法。
- 前記第2のアミノグリコシドが、静脈内投与される、請求項52に記載の方法。
- 前記第2のアミノグリコシドが、吸入を介して投与される、請求項52に記載の方法。
- 前記第2のアミノグリコシドが、ストレプトマイシンである、請求項51〜54のいずれか一項に記載の方法。
- 前記1つまたは複数の追加の治療剤が、エタンブトールである、請求項39に記載の方法。
- 前記1つまたは複数の追加の治療剤が、イソニアジドである、請求項39に記載の方法。
- 前記1つまたは複数の追加の治療剤が、セフォキシチンである、請求項39に記載の方法。
- 前記1つまたは複数の追加の治療剤が、イミペネムである、請求項39に記載の方法。
- 前記1つまたは複数の追加の治療剤が、チゲサイクリンである、請求項39に記載の方法。
- キノロンが、シプロフロキサシンである、請求項49に記載の方法。
- キノロンが、レボフロキサシンである、請求項49に記載の方法。
- キノロンが、ガチフロキサシンである、請求項49に記載の方法。
- キノロンが、エノキサシンである、請求項49に記載の方法。
- キノロンが、レボフロキサシンである、請求項49に記載の方法。
- キノロンが、オフロキサシンである、請求項49に記載の方法。
- キノロンが、モキシフロキサシンである、請求項49に記載の方法。
- キノロンが、トロバフロキサシンである、請求項49に記載の方法。
- 投与期間の間または投与期間の後、患者がNTM培養の陰性転化を示す、請求項1〜68のいずれか一項に記載の方法。
- NTM培養の陰性転化までの時間が、約10日間、約20日間、約30日間、約40日間、約50日間、約60日間、約70日間、約80日間、約90日間、約100日間または約110日間である、請求項69に記載の方法。
- NTM培養の陰性転化までの時間が、約20日間〜約200日間、約20日間〜約190日間、約20日間〜約180日間、約20日間〜約160日間、約20日間〜約150日間、約20日間〜約140日間、約20日間〜約130日間、約20日間〜約120日間、約20日間〜約110日間、約30日間〜約110日間、または約30日間〜約100日間である、請求項69に記載の方法。
- 患者が、投与期間終了後少なくとも15日間、投与期間前の患者のFEV1に比べてFEV1の改善を経験する、請求項1〜71のいずれか一項に記載の方法。
- 患者が、投与期間終了後少なくとも15日間、投与期間前の患者の血中酸素飽和度に比べて血中酸素飽和度の改善を経験する、請求項1〜72のいずれか一項に記載の方法。
- 患者のFEV1が、投与期間前の患者のFEV1よりも少なくとも5%増加する、請求項72に記載の方法。
- 患者のFEV1が、投与期間前の患者のFEV1よりも少なくとも10%増加する、請求項72に記載の方法。
- 患者のFEV1が、投与期間前の患者のFEV1よりも少なくとも15%増加する、請求項72に記載の方法。
- 患者のFEV1が、投与期間前のFEV1よりも5%〜50%増加する、請求項72に記載の方法。
- 患者が、治療方法を受ける前に患者が歩いたメートル数に比べて増加した、6分間歩行試験(6MWT)において歩いたメートル数を示す、請求項1〜77のいずれか一項に記載の方法。
- 増加した6MWTにおいて歩いたメートル数が、一実施形態において、少なくとも約5メートルである、請求項78に記載の方法。
- 増加した6MWTにおいて歩いたメートル数が、一実施形態において、少なくとも約10メートルである、請求項78に記載の方法。
- 増加した6MWTにおいて歩いたメートル数が、一実施形態において、少なくとも約20メートルである、請求項78に記載の方法。
- 増加した6MWTにおいて歩いたメートル数が、一実施形態において、少なくとも約30メートルである、請求項78に記載の方法。
- 増加した6MWTにおいて歩いたメートル数が、一実施形態において、少なくとも約40メートルである、請求項78に記載の方法。
- 増加した6MWTにおいて歩いたメートル数が、一実施形態において、少なくとも約50メートルである、請求項78に記載の方法。
- 増加した6MWTにおいて歩いたメートル数が、一実施形態において、約5メートル〜約50メートルである、請求項78に記載の方法。
- 増加した6MWTにおいて歩いたメートル数が、一実施形態において、約15メートル〜約50メートルである、請求項78に記載の方法。
- 患者が、NTM肺感染症のための非リポソームアミノグリコシド治療に供された患者に比べてより多い、6MWTにおいて歩いたメートル数を示す、請求項1〜86のいずれか一項に記載の方法。
- より多いメートル数が、少なくとも約5メートル、少なくとも約10メートル、少なくとも約15メートル、少なくとも約20メートル、少なくとも約25メートル、少なくとも約30メートル、少なくとも約35メートル、少なくとも約40メートル、少なくとも約45メートル、または少なくとも約50メートルである、請求項87に記載の方法。
- より多いメートル数が、約5メートル〜約80メートル、約5メートル〜約70メートル、約5メートル〜約60メートルまたは約5メートル〜約50メートルである、請求項87に記載の方法。
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Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8226975B2 (en) | 2005-12-08 | 2012-07-24 | Insmed Incorporated | Lipid-based compositions of antiinfectives for treating pulmonary infections and methods of use thereof |
US9119783B2 (en) | 2007-05-07 | 2015-09-01 | Insmed Incorporated | Method of treating pulmonary disorders with liposomal amikacin formulations |
EP2925298B1 (en) | 2012-11-29 | 2019-05-29 | Insmed Incorporated | Stabilized vancomycin formulations |
NO2699580T3 (ja) | 2014-01-24 | 2018-02-24 | ||
EP3466432B1 (en) | 2014-05-15 | 2020-07-08 | Insmed Incorporated | Methods for treating pulmonary non-tuberculous mycobacterial infections |
EP3490566A4 (en) * | 2016-07-29 | 2020-03-11 | Insmed Incorporated | DETERMINED (2S) -N - [(1S)] - 1-CYANO-2-PHENYLETHYL-1,4-OXAZEPAN-2-CARBOXAMIDES FOR TREATING BRONCHIEKTASIS |
WO2018186998A1 (en) * | 2017-04-05 | 2018-10-11 | Aradigm Corporation | Liposomal anti-infective formulations to inhibit non-tuberculous mycobacteria (ntm) microaggregate formation and establishment of ntm biofilm |
BR112020007395A2 (pt) * | 2017-10-16 | 2020-09-29 | Drugrecure Aps | uso do fator estimulador de colônias de granulócitos e macrófagos, e, método de tratamento de uma infecção pulmonar por micobactérias não tuberculosas refratária |
CN108310393A (zh) * | 2018-02-12 | 2018-07-24 | 丹诺医药(苏州)有限公司 | 一种利福霉素-喹嗪酮偶联分子的应用 |
WO2019191627A1 (en) | 2018-03-30 | 2019-10-03 | Insmed Incorporated | Methods for continuous manufacture of liposomal drug products |
US10736847B2 (en) * | 2018-07-03 | 2020-08-11 | Becton, Dickinson And Company | Inverting device for liposome preparation by centrifugation |
US20220081470A1 (en) * | 2019-01-05 | 2022-03-17 | Foundation For Neglected Disease Research | Thiazolyl peptides for the treatment nontuberculous mycobacterial infections |
KR102275997B1 (ko) * | 2019-11-07 | 2021-07-13 | 연세대학교 산학협력단 | 숙주지향치료를 위한 조성물 |
US11808135B2 (en) | 2020-01-16 | 2023-11-07 | Halliburton Energy Services, Inc. | Systems and methods to perform a downhole inspection in real-time |
WO2022039506A1 (ko) * | 2020-08-19 | 2022-02-24 | 주식회사 미토이뮨테라퓨틱스 | Mabc-r 감염에 의한 병적 염증 치료제로서의 미토콘드리아 표적 항산화제 |
AU2021334377A1 (en) * | 2020-08-31 | 2023-03-02 | Insmed Incorporated | Methods for treating newly diagnosed mycobacterium avium complex lung infections |
EP4313066A1 (en) * | 2021-03-24 | 2024-02-07 | Insmed Incorporated | Combination therapy for treating non-tuberculous mycobacterial lung disease |
WO2022261459A1 (en) * | 2021-06-11 | 2022-12-15 | Colorado State University Research Foundation | Compositions and methods for treating non-tuberculous mycobacterial infections |
KR102596057B1 (ko) * | 2021-11-05 | 2023-11-01 | 연세대학교 산학협력단 | 마이코박테리움 아비움 복합체 감염질환 진단용 지질대사체 마커 |
KR102615869B1 (ko) * | 2021-11-05 | 2023-12-21 | 연세대학교 산학협력단 | 마이코박테리움 아비움 복합체 폐질환 환자의 정보에 따른 치료 반응 예측용 지질대사체 마커 |
WO2023080663A1 (ko) * | 2021-11-05 | 2023-05-11 | 연세대학교 산학협력단 | 마이코박테리움 아비움 복합체 감염질환 진단 또는 중증도 예측용 대사체 마커 |
KR102613631B1 (ko) * | 2021-11-05 | 2023-12-15 | 연세대학교 산학협력단 | 마이코박테리움 아비움 복합체 감염증의 중증도 예측용 대사체 마커 |
WO2023107923A1 (en) * | 2021-12-07 | 2023-06-15 | An2 Therapeutics, Inc. | Combinations |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012505265A (ja) * | 2008-10-13 | 2012-03-01 | インスメッド インコーポレイテッド | リポソームアミカシン処方物による肺疾患の治療方法 |
WO2013177226A1 (en) * | 2012-05-21 | 2013-11-28 | Insmed Incorporated | Systems for treating pulmonary infections |
WO2014025890A1 (en) * | 2012-08-10 | 2014-02-13 | University Of North Texas Health Science Center | Drug delivery vehicle comprising conjugates between targeting polyamino acids and fatty acids |
JP6646653B2 (ja) * | 2014-05-15 | 2020-02-14 | インスメッド インコーポレイテッド | 非結核性抗酸菌肺感染症を治療するための方法 |
Family Cites Families (354)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3006698A (en) | 1959-11-25 | 1961-10-31 | Gen Motors Corp | Bearing assembly |
US3061303A (en) | 1961-02-21 | 1962-10-30 | Didde Glaser Inc | Self-centering parallel guide assembly |
US3091572A (en) | 1962-07-16 | 1963-05-28 | Schering Corp | Gentamycin and method of production |
US3136704A (en) | 1962-12-05 | 1964-06-09 | Schering Corp | Manufacture of gentamycin |
US3852557A (en) | 1973-07-12 | 1974-12-03 | Cutler Hammer Inc | Electric switch with pivoting and wiping movable contractor |
US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4394448A (en) | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
GB2046092B (en) | 1979-03-05 | 1983-11-02 | Toyama Chemical Co Ltd | Pharmaceutical composition containing a lysophospholid and a phospholipid |
HU184141B (en) | 1979-12-27 | 1984-07-30 | Human Oltoanyagtermelo | Adjuvant particles compositions containing said particles and biologically active substances adsorbed thereon and a process for the preparation thereof |
US4451447A (en) | 1980-03-31 | 1984-05-29 | Bristol-Myers Company | Pharmaceutical formulations |
ATE18353T1 (de) | 1981-07-02 | 1986-03-15 | Hoffmann La Roche | Verfahren zur herstellung von liposomenloesungen. |
US4547490A (en) | 1981-12-31 | 1985-10-15 | Neomed, Inc. | Synthetic whole blood and a method of making the same |
US4522803A (en) | 1983-02-04 | 1985-06-11 | The Liposome Company, Inc. | Stable plurilamellar vesicles, their preparation and use |
US4684625A (en) | 1982-07-08 | 1987-08-04 | Syntex (U.S.A.) Inc. | Method for enhancing the anti-infective activity of muramyldipeptide derivatives |
US5030453A (en) | 1983-03-24 | 1991-07-09 | The Liposome Company, Inc. | Stable plurilamellar vesicles |
US4981692A (en) | 1983-03-24 | 1991-01-01 | The Liposome Company, Inc. | Therapeutic treatment by intramammary infusion |
US5169637A (en) | 1983-03-24 | 1992-12-08 | The Liposome Company, Inc. | Stable plurilamellar vesicles |
US4588578A (en) | 1983-08-08 | 1986-05-13 | The Liposome Company, Inc. | Lipid vesicles prepared in a monophase |
US4515736A (en) | 1983-05-12 | 1985-05-07 | The Regents Of The University Of California | Method for encapsulating materials into liposomes |
US5059591B1 (en) | 1983-05-26 | 2000-04-25 | Liposome Co Inc | Drug preparations of reduced toxicity |
CA1237670A (en) | 1983-05-26 | 1988-06-07 | Andrew S. Janoff | Drug preparations of reduced toxicity |
US4606939A (en) | 1983-06-22 | 1986-08-19 | The Ohio State University Research Foundation | Small particle formation |
CA1237671A (en) | 1983-08-01 | 1988-06-07 | Michael W. Fountain | Enhancement of pharmaceutical activity |
GB8322178D0 (en) | 1983-08-17 | 1983-09-21 | Sterwin Ag | Preparing aerosol compositions |
WO1985000968A1 (en) | 1983-09-06 | 1985-03-14 | Health Research, Inc. | Liposome delivery method for decreasing the toxicity of an antitumor drug |
US4721612A (en) | 1984-04-12 | 1988-01-26 | The Liposome Company, Inc. | Steroidal liposomes |
US4963367A (en) | 1984-04-27 | 1990-10-16 | Medaphore, Inc. | Drug delivery compositions and methods |
US4794000A (en) | 1987-01-08 | 1988-12-27 | Synthetic Blood Corporation | Coacervate-based oral delivery system for medically useful compositions |
US5008050A (en) | 1984-06-20 | 1991-04-16 | The Liposome Company, Inc. | Extrusion technique for producing unilamellar vesicles |
SE8403905D0 (sv) | 1984-07-30 | 1984-07-30 | Draco Ab | Liposomes and steroid esters |
US4880635B1 (en) | 1984-08-08 | 1996-07-02 | Liposome Company | Dehydrated liposomes |
US5077056A (en) | 1984-08-08 | 1991-12-31 | The Liposome Company, Inc. | Encapsulation of antineoplastic agents in liposomes |
US5736155A (en) | 1984-08-08 | 1998-04-07 | The Liposome Company, Inc. | Encapsulation of antineoplastic agents in liposomes |
JPS63500175A (ja) | 1985-05-22 | 1988-01-21 | リポソ−ム テクノロジ−,インコ−ポレイテツド | リポソ−ム吸入法および吸入システム |
US5059421A (en) | 1985-07-26 | 1991-10-22 | The Liposome Company, Inc. | Preparation of targeted liposome systems of a defined size distribution |
US5409704A (en) | 1985-06-26 | 1995-04-25 | The Liposome Company, Inc. | Liposomes comprising aminoglycoside phosphates and methods of production and use |
US4975282A (en) | 1985-06-26 | 1990-12-04 | The Liposome Company, Inc. | Multilamellar liposomes having improved trapping efficiencies |
DE3689769T2 (de) | 1985-07-05 | 1994-07-21 | Liposome Co Inc | Multilamellare liposome mit verbesserter einschliessungswirkung. |
JPH0665648B2 (ja) | 1985-09-25 | 1994-08-24 | 塩野義製薬株式会社 | 白金系抗癌物質の安定な凍結真空乾燥製剤 |
US5041278A (en) | 1985-10-15 | 1991-08-20 | The Liposome Company, Inc. | Alpha tocopherol-based vesicles |
US4861580A (en) | 1985-10-15 | 1989-08-29 | The Liposome Company, Inc. | Composition using salt form of organic acid derivative of alpha-tocopheral |
US5041581A (en) | 1985-10-18 | 1991-08-20 | The University Of Texas System Board Of Regents | Hydrophobic cis-platinum complexes efficiently incorporated into liposomes |
US5023087A (en) | 1986-02-10 | 1991-06-11 | Liposome Technology, Inc. | Efficient method for preparation of prolonged release liposome-based drug delivery system |
US6759057B1 (en) | 1986-06-12 | 2004-07-06 | The Liposome Company, Inc. | Methods and compositions using liposome-encapsulated non-steroidal anti-inflammatory drugs |
US4833134A (en) | 1986-08-19 | 1989-05-23 | Takeda Chemical Industries, Ltd. | Cephem compounds |
US5049388A (en) | 1986-11-06 | 1991-09-17 | Research Development Foundation | Small particle aerosol liposome and liposome-drug combinations for medical use |
US4933121A (en) | 1986-12-10 | 1990-06-12 | Ciba Corning Diagnostics Corp. | Process for forming liposomes |
US5320906A (en) | 1986-12-15 | 1994-06-14 | Vestar, Inc. | Delivery vehicles with amphiphile-associated active ingredient |
ATE87503T1 (de) | 1986-12-23 | 1993-04-15 | Liposome Co Inc | Liposomes praeparat und antibiotikum. |
US5723147A (en) | 1987-02-23 | 1998-03-03 | Depotech Corporation | Multivesicular liposomes having a biologically active substance encapsulated therein in the presence of a hydrochloride |
MX9203808A (es) | 1987-03-05 | 1992-07-01 | Liposome Co Inc | Formulaciones de alto contenido de medicamento: lipido, de agentes liposomicos-antineoplasticos. |
US5616334A (en) | 1987-03-05 | 1997-04-01 | The Liposome Company, Inc. | Low toxicity drug-lipid systems |
ATE113468T1 (de) | 1987-07-29 | 1994-11-15 | Liposome Co Inc | Verfahren zur trennung von teilchen nach grösse. |
US4857311A (en) | 1987-07-31 | 1989-08-15 | Massachusetts Institute Of Technology | Polyanhydrides with improved hydrolytic degradation properties |
US4895452A (en) | 1988-03-03 | 1990-01-23 | Micro-Pak, Inc. | Method and apparatus for producing lipid vesicles |
MX9203504A (es) | 1988-04-20 | 1992-07-01 | Liposome Co Inc | Complejo agente: lipido activo de alta proporcion. |
US5269979A (en) | 1988-06-08 | 1993-12-14 | Fountain Pharmaceuticals, Inc. | Method for making solvent dilution microcarriers |
IL91664A (en) | 1988-09-28 | 1993-05-13 | Yissum Res Dev Co | Ammonium transmembrane gradient system for efficient loading of liposomes with amphipathic drugs and their controlled release |
BE1001869A3 (fr) | 1988-10-12 | 1990-04-03 | Franz Legros | Procede d'encapsulation liposomiale d'antibiotiques aminoglucosidiques, en particulier de la gentamycine. |
US4952405A (en) * | 1988-10-20 | 1990-08-28 | Liposome Technology, Inc. | Method of treating M. avium infection |
US4906476A (en) | 1988-12-14 | 1990-03-06 | Liposome Technology, Inc. | Novel liposome composition for sustained release of steroidal drugs in lungs |
US5006343A (en) | 1988-12-29 | 1991-04-09 | Benson Bradley J | Pulmonary administration of pharmaceutically active substances |
US5843473A (en) | 1989-10-20 | 1998-12-01 | Sequus Pharmaceuticals, Inc. | Method of treatment of infected tissues |
WO1991009616A1 (en) | 1989-12-22 | 1991-07-11 | Yale University | Quinolone antibiotics encapsulated in lipid vesicles |
US5542935A (en) | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
US5580575A (en) | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
US5820848A (en) | 1990-01-12 | 1998-10-13 | The Liposome Company, Inc. | Methods of preparing interdigitation-fusion liposomes and gels which encapsulate a bioactive agent |
US5279833A (en) | 1990-04-04 | 1994-01-18 | Yale University | Liposomal transfection of nucleic acids into animal cells |
US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
AU7908791A (en) | 1990-05-08 | 1991-11-27 | Liposome Technology, Inc. | Direct spray-dried drug/lipid powder composition |
US6623671B2 (en) | 1990-10-05 | 2003-09-23 | Royden M. Coe | Liposome extrusion process |
US5614216A (en) | 1990-10-17 | 1997-03-25 | The Liposome Company, Inc. | Synthetic lung surfactant |
IT1245761B (it) | 1991-01-30 | 1994-10-14 | Alfa Wassermann Spa | Formulazioni farmaceutiche contenenti glicosaminoglicani assorbibili per via orale. |
ES2084335T3 (es) | 1991-02-14 | 1996-05-01 | Baxter Int | Union de sustancias de reconocimiento a liposomas. |
US5228346A (en) | 1991-04-08 | 1993-07-20 | Marathon Oil Company | Method of determining gas flow volume |
US6629646B1 (en) | 1991-04-24 | 2003-10-07 | Aerogen, Inc. | Droplet ejector with oscillating tapered aperture |
EP0540775B1 (de) | 1991-11-07 | 1997-07-23 | PAUL RITZAU PARI-WERK GmbH | Vernebler insbesondere zur Anwendung in Geräten für die Inhalationstherapie |
US5770563A (en) | 1991-12-06 | 1998-06-23 | The United States Of America As Represented By The Department Of Health And Human Services | Heparin- and sulfatide binding peptides from the type I repeats of human thrombospondin and conjugates thereof |
WO1993012240A1 (en) | 1991-12-17 | 1993-06-24 | The Regents Of The University Of California | Gene therapy for cystic fibrosis transmembrane conductance regulator activity (cftr) |
US5858784A (en) | 1991-12-17 | 1999-01-12 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol- and liposome-based delivery |
US5756353A (en) | 1991-12-17 | 1998-05-26 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol-and liposome-based delivery |
US6890555B1 (en) | 1992-02-05 | 2005-05-10 | Qlt, Inc. | Liposome compositions of porphyrin photosensitizers |
US5334761A (en) | 1992-08-28 | 1994-08-02 | Life Technologies, Inc. | Cationic lipids |
US5871710A (en) | 1992-09-04 | 1999-02-16 | The General Hospital Corporation | Graft co-polymer adducts of platinum (II) compounds |
AU3244393A (en) * | 1992-12-02 | 1994-06-22 | Vestar, Inc. | Antibiotic formulation and process |
US5958449A (en) | 1992-12-02 | 1999-09-28 | Nexstar Pharmaceuticals, Inc. | Antibiotic formulation and use for bacterial infections |
US5665383A (en) | 1993-02-22 | 1997-09-09 | Vivorx Pharmaceuticals, Inc. | Methods for the preparation of immunostimulating agents for in vivo delivery |
US5395619A (en) | 1993-03-03 | 1995-03-07 | Liposome Technology, Inc. | Lipid-polymer conjugates and liposomes |
ZA938381B (en) | 1993-03-22 | 1994-06-13 | Inland Steel Co | Apparatus and method for magnetically confining molten metal using concentrating fins |
CA2120197A1 (en) | 1993-04-02 | 1994-10-03 | Kenji Endo | Stable aqueous dispersions containing liposomes |
JPH09502700A (ja) | 1993-04-02 | 1997-03-18 | ザ リポソーム カンパニー、インコーポレーテッド | リポソームの製造方法 |
US5759571A (en) | 1993-05-11 | 1998-06-02 | Nexstar Pharmaceuticals, Inc. | Antibiotic formulation and use for drug resistant infections |
US5497763A (en) | 1993-05-21 | 1996-03-12 | Aradigm Corporation | Disposable package for intrapulmonary delivery of aerosolized formulations |
JPH06345663A (ja) | 1993-06-08 | 1994-12-20 | Sumitomo Pharmaceut Co Ltd | バンコマイシン含有リポソーム製剤 |
DK0707472T3 (da) | 1993-07-08 | 2001-04-17 | Liposome Co Inc | Fremgangsmåde til regulering af størrelsen af liposomer |
CA2101241C (en) | 1993-07-23 | 1998-12-22 | Jonathan P. Wong | Liposome-encapsulated ciprofloxacin |
WO1995012387A1 (en) | 1993-11-05 | 1995-05-11 | Amgen Inc. | Liposome preparation and material encapsulation method |
US5766627A (en) | 1993-11-16 | 1998-06-16 | Depotech | Multivescular liposomes with controlled release of encapsulated biologically active substances |
EP0741580A4 (en) | 1993-12-14 | 2001-07-11 | Univ Johns Hopkins Med | CONTROLLED RELEASE OF PHARMACEUTICALLY ACTIVE SUBSTANCES FOR IMMUNOTHERAPY |
EP0663241B1 (de) | 1993-12-17 | 1998-07-15 | PARI GmbH Spezialisten für effektive Inhalation | Zerstäuberdüse |
AU710504B2 (en) | 1994-03-15 | 1999-09-23 | Brown University Research Foundation | Polymeric gene delivery system |
US5610198A (en) | 1994-03-18 | 1997-03-11 | The United States Of America As Represented By The Department Of Health And Human Services | Anti-mycobacterial compositions and their use for the treatment of tuberculosis and related diseases |
DE59409856D1 (de) | 1994-05-19 | 2001-10-11 | Pari Gmbh | Vorrichtung zur Trocknung und Pufferung von Aerosolen |
US5550109A (en) | 1994-05-24 | 1996-08-27 | Magainin Pharmaceuticals Inc. | Inducible defensin peptide from mammalian epithelia |
US5543152A (en) | 1994-06-20 | 1996-08-06 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
US5741516A (en) | 1994-06-20 | 1998-04-21 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
US5993850A (en) | 1994-09-13 | 1999-11-30 | Skyepharma Inc. | Preparation of multivesicular liposomes for controlled release of encapsulated biologically active substances |
US5753613A (en) | 1994-09-30 | 1998-05-19 | Inex Pharmaceuticals Corporation | Compositions for the introduction of polyanionic materials into cells |
US5508269A (en) | 1994-10-19 | 1996-04-16 | Pathogenesis Corporation | Aminoglycoside formulation for aerosolization |
US6000394A (en) | 1994-10-26 | 1999-12-14 | Paul Rizau Pari-Werk Gmbh | Generation of an aerosol of an exact dose |
SA95160463B1 (ar) | 1994-12-22 | 2005-10-04 | استرا أكتيبولاج | مساحيق للاستنشاق |
US5662929A (en) | 1994-12-23 | 1997-09-02 | Universite De Montreal | Therapeutic liposomal formulation |
US5883074A (en) | 1995-02-08 | 1999-03-16 | Microcide Pharmaceuticals, Inc. | Potentiators of antibacterial agents |
US5972379A (en) | 1995-02-14 | 1999-10-26 | Sequus Pharmaceuticals, Inc. | Liposome composition and method for administering a quinolone |
US5800833A (en) | 1995-02-27 | 1998-09-01 | University Of British Columbia | Method for loading lipid vesicles |
DE69632859T2 (de) | 1995-04-18 | 2005-07-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Verfahren zur Arzneistoffbehandlung von Liposomen Zusammensetzung |
US5855610A (en) | 1995-05-19 | 1999-01-05 | Children's Medical Center Corporation | Engineering of strong, pliable tissues |
CA2220950A1 (en) | 1995-05-26 | 1996-11-28 | Somatix Therapy Corporation | Delivery vehicles comprising stable lipid/nucleic acid complexes |
DE19520622C2 (de) | 1995-06-06 | 2003-05-15 | Pari Gmbh | Vorrichtung zum Vernebeln von Fluiden |
MX9701731A (es) | 1995-06-06 | 1997-10-31 | Bayer Ag | Composiciones anti-bacterianas oticas, no-irritantes, no-sensibles y no-toxicas para el oido. |
US5643599A (en) | 1995-06-07 | 1997-07-01 | President And Fellows Of Harvard College | Intracellular delivery of macromolecules |
US6521211B1 (en) | 1995-06-07 | 2003-02-18 | Bristol-Myers Squibb Medical Imaging, Inc. | Methods of imaging and treatment with targeted compositions |
JPH11507697A (ja) | 1995-06-09 | 1999-07-06 | エヌ. ドロハン,ウィリアム | キチンヒドロゲル、それらの製造方法及び利用 |
US5942253A (en) | 1995-10-12 | 1999-08-24 | Immunex Corporation | Prolonged release of GM-CSF |
WO1997014740A1 (en) | 1995-10-19 | 1997-04-24 | Receptagen Corporation | Discrete-length polyethylene glycols |
DE19602628C2 (de) | 1996-01-25 | 2000-06-29 | Pari Gmbh | Vernebler |
GB9602969D0 (en) | 1996-02-13 | 1996-04-10 | The Technology Partnership Plc | Liquid supply apparatus |
US5840702A (en) | 1996-03-22 | 1998-11-24 | Uab Research Foundation | Cystic fibrosis treatment |
AU733212B2 (en) | 1996-03-28 | 2001-05-10 | Board Of Trustees Of The University Of Illinois, The | Material and methods for making improved liposome compositions |
US5875776A (en) | 1996-04-09 | 1999-03-02 | Vivorx Pharmaceuticals, Inc. | Dry powder inhaler |
US6132765A (en) | 1996-04-12 | 2000-10-17 | Uroteq Inc. | Drug delivery via therapeutic hydrogels |
CA2174803C (en) | 1996-04-23 | 2000-07-11 | Jonathan P. Wong | Use of liposome encapsulated ciprofloxacin as an immunotherapeutic drug |
DE19616573C2 (de) | 1996-04-25 | 1999-03-04 | Pari Gmbh | Verwendung unterkritischer Treibmittelmischungen und Aerosole für die Mikronisierung von Arzneimitteln mit Hilfe dichter Gase |
DE69722793T2 (de) | 1996-04-26 | 2004-05-19 | Genaera Corp. | Squalamin in kombination mit anderen antikrebs-mittelen zur behandlung von tumoren |
GB9609779D0 (en) | 1996-05-10 | 1996-07-17 | Univ Bruxelles | Freeze dried liposome encapsulated amphiphilic drug compositions and a process for the preparation thereof |
US6254854B1 (en) | 1996-05-24 | 2001-07-03 | The Penn Research Foundation | Porous particles for deep lung delivery |
US6770291B2 (en) | 1996-08-30 | 2004-08-03 | The United States Of America As Represented By The Department Of Health And Human Services | Liposome complexes for increased systemic delivery |
US6503881B2 (en) | 1996-08-21 | 2003-01-07 | Micrologix Biotech Inc. | Compositions and methods for treating infections using cationic peptides alone or in combination with antibiotics |
DE69725747T2 (de) | 1996-08-23 | 2004-07-29 | Sequus Pharmaceuticals, Inc., Menlo Park | Liposome enthaltend cisplatin |
TW520297B (en) | 1996-10-11 | 2003-02-11 | Sequus Pharm Inc | Fusogenic liposome composition and method |
US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
US5837282A (en) | 1996-10-30 | 1998-11-17 | University Of British Columbia | Ionophore-mediated liposome loading |
WO1998029110A2 (en) | 1996-12-30 | 1998-07-09 | Battelle Memorial Institute | Formulation and method for treating neoplasms by inhalation |
US6451784B1 (en) | 1996-12-30 | 2002-09-17 | Battellepharma, Inc. | Formulation and method for treating neoplasms by inhalation |
US6458373B1 (en) | 1997-01-07 | 2002-10-01 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
DE19713636A1 (de) | 1997-04-02 | 1998-10-08 | Pari Gmbh | Atemzugsimulator |
US20020039594A1 (en) | 1997-05-13 | 2002-04-04 | Evan C. Unger | Solid porous matrices and methods of making and using the same |
US5957339A (en) | 1997-06-23 | 1999-09-28 | Keystone Manufacturing Co., Inc. | Water filtration system |
JP4142149B2 (ja) | 1997-07-10 | 2008-08-27 | 明治製菓株式会社 | バンコマイシンの凍結乾燥製剤 |
DE19734022C2 (de) | 1997-08-06 | 2000-06-21 | Pari Gmbh | Inhalationstherapiegerät mit einem Ventil zur Begrenzung des Inspirationsflusses |
US6106858A (en) | 1997-09-08 | 2000-08-22 | Skyepharma, Inc. | Modulation of drug loading in multivescular liposomes |
CA2215716C (en) | 1997-09-17 | 1999-12-07 | Her Majesty The Queen, In Right Of Canada, As Represented By The Ministe R Of National Defence | Aerosol delivery of liposome-encapsulated fluoroquinolone |
US6090407A (en) | 1997-09-23 | 2000-07-18 | Research Development Foundation | Small particle liposome aerosols for delivery of anti-cancer drugs |
DE19746287A1 (de) | 1997-10-20 | 1999-04-22 | Hoechst Marion Roussel De Gmbh | Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
AP2000001805A0 (en) | 1997-10-22 | 2000-06-30 | Jens Ponikau | Use of antifungal agents for the topical treatment of fungus-induced mucositis. |
CA2309548A1 (en) | 1997-11-14 | 1999-05-27 | Skyepharma Inc. | Production of multivesicular liposomes |
US6051251A (en) | 1997-11-20 | 2000-04-18 | Alza Corporation | Liposome loading method using a boronic acid compound |
AU1656799A (en) | 1997-12-12 | 1999-07-05 | Inex Pharmaceuticals Corp. | Cationic drugs encapsulated in anionic liposomes |
GB9827370D0 (en) | 1998-01-16 | 1999-02-03 | Pari Gmbh | Mouthpiece for inhalation therapy units |
US6468532B1 (en) | 1998-01-22 | 2002-10-22 | Genentech, Inc. | Methods of treating inflammatory diseases with anti-IL-8 antibody fragment-polymer conjugates |
US20020086852A1 (en) | 1998-05-14 | 2002-07-04 | Cantor Jerome O. | Method for treating respiratory disorders associated with pulmonary elastic fiber injury |
CA2332369A1 (en) | 1998-05-27 | 1999-12-02 | Euroceltique S.A. | Drug delivery system comprising a tightly compacted solid medicament stock |
DE19827228C2 (de) | 1998-06-18 | 2000-07-13 | Pari Gmbh | Flüssigkeitszerstäubervorrichtung |
US6200598B1 (en) | 1998-06-18 | 2001-03-13 | Duke University | Temperature-sensitive liposomal formulation |
US6509323B1 (en) | 1998-07-01 | 2003-01-21 | California Institute Of Technology | Linear cyclodextrin copolymers |
US6916490B1 (en) | 1998-07-23 | 2005-07-12 | UAB Research Center | Controlled release of bioactive substances |
CA2340118C (en) | 1998-08-12 | 2009-01-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Liposomal bupivacaine compositions prepared using an ammonium sulfate gradient |
DE19846382C1 (de) | 1998-10-08 | 2000-07-06 | Pari Gmbh | Zählwerk und seine Verwendung in Inhalatoren, Verneblern oder ähnlichen Dosieraerosolvorrichtungen |
ATE353630T1 (de) | 1998-11-12 | 2007-03-15 | Transave Inc | Inhalationssystem |
IL143104A (en) | 1998-11-13 | 2005-09-25 | Optime Therapeutics Inc | Method and apparatus for liposome production |
US6855296B1 (en) | 1998-11-13 | 2005-02-15 | Optime Therapeutics, Inc. | Method and apparatus for liposome production |
HUP0105226A3 (en) | 1998-12-17 | 2003-03-28 | Pathogenesis Corp Seattle | Method for the treatment of severe chronic bronchitis (bronchiectasis) with an aerosolized antibiotic |
US6211162B1 (en) | 1998-12-30 | 2001-04-03 | Oligos Etc. Inc. | Pulmonary delivery of protonated/acidified nucleic acids |
JP2002536316A (ja) | 1999-02-08 | 2002-10-29 | アルザ・コーポレーション | リポソームサイズを調節する方法 |
WO2000059528A1 (en) | 1999-04-02 | 2000-10-12 | The Trustees Of Princeton University | Desleucyl glycopeptide antibiotics and methods of making same |
US6613352B2 (en) | 1999-04-13 | 2003-09-02 | Universite De Montreal | Low-rigidity liposomal formulation |
US7297344B1 (en) | 1999-05-27 | 2007-11-20 | Euro-Celtique, S.A. | Preparations for the promotion of wound healing in the upper respiratory tract and/or ear |
US6599912B1 (en) | 1999-06-03 | 2003-07-29 | Jessie L. -S. Au | Methods and compositions for modulating cell proliferation and cell death |
CA2376849C (en) | 1999-06-24 | 2008-10-14 | Kyowa Hakko Kogyo Co., Ltd. | Method of inhibiting leakage of drug encapsulated in liposomes |
JP5388395B2 (ja) | 1999-07-15 | 2014-01-15 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | 脂質に被包された治療剤の製造方法 |
US6352996B1 (en) | 1999-08-03 | 2002-03-05 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
US6174878B1 (en) | 1999-08-31 | 2001-01-16 | Alcon Laboratories, Inc. | Topical use of kappa opioid agonists to treat otic pain |
US6235177B1 (en) | 1999-09-09 | 2001-05-22 | Aerogen, Inc. | Method for the construction of an aperture plate for dispensing liquid droplets |
US6511676B1 (en) | 1999-11-05 | 2003-01-28 | Teni Boulikas | Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes |
US6962151B1 (en) | 1999-11-05 | 2005-11-08 | Pari GmbH Spezialisten für effektive Inhalation | Inhalation nebulizer |
DE19953317C1 (de) | 1999-11-05 | 2001-02-01 | Pari Gmbh | Inhalationsvernebler |
JP4198850B2 (ja) | 1999-11-29 | 2008-12-17 | オムロンヘルスケア株式会社 | 液体噴霧装置 |
JP2003515568A (ja) | 1999-12-04 | 2003-05-07 | リサーチ ディベロップメント ファンデーション | 吸入療法における二酸化炭素増強 |
DE10004465A1 (de) | 2000-02-02 | 2001-08-16 | Pari Gmbh | Inhalationsvernebler |
ES2272496T3 (es) | 2000-02-04 | 2007-05-01 | Lipoxen Technologies Limited | Procedimiento de deshidratacion/rehidritacion para la preparacion de lipososmas. |
US6761877B2 (en) | 2000-02-18 | 2004-07-13 | Biocrystal, Ltd. | Functionalized encapsulated fluorescent nanocrystals |
US7758888B2 (en) | 2000-04-21 | 2010-07-20 | Sol-Gel Technologies Ltd. | Composition exhibiting enhanced formulation stability and delivery of topical active ingredients |
US7600511B2 (en) | 2001-11-01 | 2009-10-13 | Novartis Pharma Ag | Apparatus and methods for delivery of medicament to a respiratory system |
US7971588B2 (en) | 2000-05-05 | 2011-07-05 | Novartis Ag | Methods and systems for operating an aerosol generator |
US7100600B2 (en) | 2001-03-20 | 2006-09-05 | Aerogen, Inc. | Fluid filled ampoules and methods for their use in aerosolizers |
US6948491B2 (en) | 2001-03-20 | 2005-09-27 | Aerogen, Inc. | Convertible fluid feed system with comformable reservoir and methods |
US8336545B2 (en) | 2000-05-05 | 2012-12-25 | Novartis Pharma Ag | Methods and systems for operating an aerosol generator |
MXPA02010884A (es) | 2000-05-05 | 2003-03-27 | Aerogen Ireland Ltd | Aparato y metodo para el suministro de medicamentos al sistema respiratorio. |
US6338859B1 (en) | 2000-06-29 | 2002-01-15 | Labopharm Inc. | Polymeric micelle compositions |
US6521736B2 (en) | 2000-09-15 | 2003-02-18 | University Of Massachusetts | Amphiphilic polymeric materials |
EP1333811A4 (en) | 2000-10-16 | 2004-03-03 | Neopharm Inc | LIPOSOMAL PREPARATION BASED ON MITOXANTRONE |
CN1116875C (zh) | 2000-10-19 | 2003-08-06 | 南京振中生物工程有限公司 | 紫杉醇脂质组合物及其制备方法 |
US6497901B1 (en) | 2000-11-02 | 2002-12-24 | Royer Biomedical, Inc. | Resorbable matrices for delivery of bioactive compounds |
EP1203614A1 (de) | 2000-11-03 | 2002-05-08 | Polymun Scientific Immunbiologische Forschung GmbH | Verfahren und Vorrichtung zur Herstellung von Lipidvesikeln |
AU2002219998B2 (en) | 2000-12-01 | 2006-03-02 | Biomira, Inc. | Preparation of large liposomes by infusion into peg |
DE10102846B4 (de) | 2001-01-23 | 2012-04-12 | Pari Pharma Gmbh | Aerosolgenerator |
US20020187105A1 (en) | 2001-02-01 | 2002-12-12 | Yiyu Zou | Polymer combinations that result in stabilized aerosols for gene delivery to the lungs |
DE10109897A1 (de) | 2001-02-21 | 2002-11-07 | Novosom Ag | Fakultativ kationische Liposomen und Verwendung dieser |
US6546927B2 (en) | 2001-03-13 | 2003-04-15 | Aerogen, Inc. | Methods and apparatus for controlling piezoelectric vibration |
JP2002318193A (ja) | 2001-04-24 | 2002-10-31 | Canon Inc | ネブライザ及び高周波誘導結合プラズマ発光分析装置 |
US6732944B2 (en) | 2001-05-02 | 2004-05-11 | Aerogen, Inc. | Base isolated nebulizing device and methods |
US6554201B2 (en) | 2001-05-02 | 2003-04-29 | Aerogen, Inc. | Insert molded aerosol generator and methods |
ES2261735T3 (es) | 2001-05-18 | 2006-11-16 | Chiron Corporation | Sistema para la administracion de una formulacion de tobramicina. |
US20030060451A1 (en) | 2001-05-29 | 2003-03-27 | Rajneesh Taneja | Enhancement of oral bioavailability of non-emulsified formulations of prodrug esters with lecithin |
DE10126808C1 (de) | 2001-06-01 | 2002-08-14 | Pari Gmbh | Inhalationsmaske |
DE10126807C2 (de) | 2001-06-01 | 2003-12-04 | Pari Gmbh | Inhalationstherapiegerät mit einem Ventil zur Begrenzung des Inspirationsflusses |
EP1269993A1 (en) | 2001-06-21 | 2003-01-02 | Applied NanoSystems B.V. | Delivery of small hydrophilic molecules packaged into lipid vesicles |
WO2003000236A1 (en) | 2001-06-23 | 2003-01-03 | Lyotropic Therapeutics, Inc | Particles with improved solubilization capacity |
AU2002323151A1 (en) | 2001-08-13 | 2003-03-03 | University Of Pittsburgh | Application of lipid vehicles and use for drug delivery |
US20030059375A1 (en) | 2001-08-20 | 2003-03-27 | Transave, Inc. | Method for treating lung cancers |
US6623723B2 (en) * | 2001-08-21 | 2003-09-23 | Cellular Sciences Inc. | Method for treating bronchial constriction and bronchospasm |
YU8804A (sh) | 2001-08-21 | 2006-08-17 | Pfizer Products Inc. | Jedno-dozni azitromicin |
DE50102690D1 (de) | 2001-10-18 | 2004-07-29 | Pari Gmbh | Inhalationstherapievorrichtung |
EP1304131B1 (de) | 2001-10-18 | 2005-06-29 | PARI GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung |
US20050119202A1 (en) | 2001-10-26 | 2005-06-02 | Roland Kreutzer | Medicament to treat a fibrotic disease |
US20030096774A1 (en) | 2001-11-21 | 2003-05-22 | Igor Gonda | Compositions of nucleic acids and cationic aminoglycosides and methods of using and preparing the same |
SI1458360T1 (sl) | 2001-12-19 | 2011-08-31 | Novartis Ag | Pulmonalno dajanje aminoglikozidov |
JP4761709B2 (ja) | 2002-01-15 | 2011-08-31 | エアロジェン,インコーポレイテッド | エアロゾル発生器を作動するための方法およびシステム |
US6845770B2 (en) | 2002-01-15 | 2005-01-25 | Aerogen, Inc. | Systems and methods for clearing aerosols from the effective anatomic dead space |
US20030224039A1 (en) | 2002-03-05 | 2003-12-04 | Transave, Inc. | Methods for entrapment of bioactive agent in a liposome or lipid complex |
US20030205226A1 (en) | 2002-05-02 | 2003-11-06 | Pre Holding, Inc. | Aerosol medication inhalation system |
WO2003097126A2 (en) | 2002-05-20 | 2003-11-27 | Aerogen, Inc. | Aerosol for medical treatment and methods |
US7901708B2 (en) | 2002-06-28 | 2011-03-08 | Protiva Biotherapeutics, Inc. | Liposomal apparatus and manufacturing methods |
DE60235883D1 (de) | 2002-08-02 | 2010-05-20 | Pari Pharma Gmbh | Vorrichtung zur Erzeugung von Flüssigkeitströpfchen |
CA2494673A1 (en) | 2002-08-02 | 2004-07-01 | Transave, Inc. | Platinum aggregates and process for producing the same |
WO2004017944A1 (en) | 2002-08-23 | 2004-03-04 | Neopharm, Inc. | Liposomal gemcitabine compositions for better drug delivery |
DE10239321B3 (de) | 2002-08-27 | 2004-04-08 | Pari GmbH Spezialisten für effektive Inhalation | Aerosoltherapievorrichtung |
KR100489701B1 (ko) | 2002-10-09 | 2005-05-16 | 주식회사 태평양 | 고농도의 트리터페노이드를 함유하는 미소화 리포좀 및 그제조방법 |
US7879351B2 (en) | 2002-10-29 | 2011-02-01 | Transave, Inc. | High delivery rates for lipid based drug formulations, and methods of treatment thereof |
AU2003304204B2 (en) | 2002-10-29 | 2009-12-24 | Insmed Incorporated | Sustained release of antiinfectives |
US7718189B2 (en) | 2002-10-29 | 2010-05-18 | Transave, Inc. | Sustained release of antiinfectives |
DE10250625A1 (de) | 2002-10-30 | 2004-05-19 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung |
WO2004047800A2 (en) | 2002-11-26 | 2004-06-10 | Gilead Sciences, Inc. | Method of drug loading in liposomes by gradient |
DE10257381B4 (de) | 2002-12-09 | 2006-09-14 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung |
US7968115B2 (en) | 2004-03-05 | 2011-06-28 | Board Of Regents, The University Of Texas System | Liposomal curcumin for treatment of cancer |
WO2004091623A1 (en) | 2003-04-08 | 2004-10-28 | Progenics Pharmaceuticals. Inc. | Pharmaceutical formulations containing methylnaltrexone |
US6900184B2 (en) | 2003-04-14 | 2005-05-31 | Wyeth Holdings Corporation | Compositions containing pipercillin and tazobactam useful for injection |
DE10320143A1 (de) | 2003-05-06 | 2004-12-16 | Pari GmbH Spezialisten für effektive Inhalation | Vernebleranschlussvorrichtung für Beatmungsgeräte oder dergleichen |
DE10322505B4 (de) | 2003-05-19 | 2009-11-05 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapiemaske und -vorrichtung für Tiere |
US8058493B2 (en) | 2003-05-21 | 2011-11-15 | Baker Hughes Incorporated | Removing amines from hydrocarbon streams |
CA2527625A1 (en) | 2003-05-30 | 2004-12-23 | Alza Corporation | Method of pulmonary administration of an agent |
US8616195B2 (en) | 2003-07-18 | 2013-12-31 | Novartis Ag | Nebuliser for the production of aerosolized medication |
KR20060036119A (ko) | 2003-08-20 | 2006-04-27 | 가부시키가이샤 로코모젠 | 시노비올린 활성 조절 작용의 검출 방법 |
GB2388581A (en) | 2003-08-22 | 2003-11-19 | Danisco | Coated aqueous beads |
DE10345950A1 (de) | 2003-10-02 | 2005-05-19 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung mit Ventil |
DE10347994A1 (de) | 2003-10-15 | 2005-06-16 | Pari GmbH Spezialisten für effektive Inhalation | Wässrige Aerosol-Zubereitung |
DE10348237A1 (de) | 2003-10-16 | 2005-05-19 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung mit einem Düsenvernebler |
WO2005044226A2 (en) | 2003-11-04 | 2005-05-19 | Nectar Therapeutics | Lipid formulations for spontaneous drug encapsulation |
DK1559431T3 (da) | 2003-12-31 | 2007-07-30 | Orthologic Corp | Farmaceutisk sammensætning til thrombinpeptidderivater |
US7452524B2 (en) | 2004-01-27 | 2008-11-18 | Gilead Sciences, Inc. | Method for improvement of tolerance for therapeutically effective agents delivered by inhalation |
US7556799B2 (en) | 2004-03-30 | 2009-07-07 | Relypsa, Inc. | Ion binding polymers and uses thereof |
DE102004016985B4 (de) | 2004-04-07 | 2010-07-22 | Pari Pharma Gmbh | Aerosolerzeugungsvorrichtung und Inhalationsvorrichtung |
JP4452799B2 (ja) | 2004-07-14 | 2010-04-21 | 独立行政法人産業技術総合研究所 | コアセルベートを活用したリポソームの製造方法 |
CA2584583A1 (en) | 2004-10-28 | 2006-05-11 | Alza Corporation | Lyophilized liposome formulations and method |
EP2199298A1 (en) | 2004-11-17 | 2010-06-23 | Protiva Biotherapeutics Inc. | Sirna silencing of Apolipoprotein B |
US8337815B2 (en) | 2004-12-23 | 2012-12-25 | Discovery Laboratories, Inc. | Pulmonary surfactant formulations |
DE102005006375B4 (de) | 2005-02-11 | 2007-10-11 | Pari GmbH Spezialisten für effektive Inhalation | Aerosolerzeugungsvorrichtung für Inhalationstherapiegeräte |
DE102005006374B3 (de) | 2005-02-11 | 2006-07-20 | Pari GmbH Spezialisten für effektive Inhalation | Aerosolerzeugungsvorrichtung und Inhalationstherapiegerät mit einer derartigen Vorrichtung |
DE102005006372B4 (de) | 2005-02-11 | 2007-11-29 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung und Verfahren zu deren Betrieb |
US20060198940A1 (en) | 2005-03-04 | 2006-09-07 | Mcmorrow David | Method of producing particles utilizing a vibrating mesh nebulizer for coating a medical appliance, a system for producing particles, and a medical appliance |
JP2006263054A (ja) | 2005-03-23 | 2006-10-05 | Konica Minolta Sensing Inc | 呼吸器系疾患関連解析データの取得方法、オキシメータシステム及びその動作プログラム、オキシメータ並びに酸素補給システム |
EP1712220A1 (en) | 2005-04-15 | 2006-10-18 | PARI GmbH Spezialisten für effektive Inhalation | Pharmaceutical aerosol composition |
UA94711C2 (uk) | 2005-05-25 | 2011-06-10 | Аэроджен, Инк. | Вібраційна система (варіанти) та спосіб її виготовлення (варіанти), спосіб вібрування пластини (варіанти), система виробництва аерозолю та спосіб лікування пацієнта |
DE102005024779B4 (de) | 2005-05-31 | 2008-02-21 | Pari GmbH Spezialisten für effektive Inhalation | Atemzuggesteuerte Inhalationstherapievorrichtung |
DE102005029498B4 (de) | 2005-06-24 | 2007-08-30 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung |
USD638117S1 (en) | 2005-06-28 | 2011-05-17 | Pari Gmbh | Inhalation therapy nebuliser |
DE102005034403B3 (de) | 2005-07-22 | 2007-02-22 | Airbus Deutschland Gmbh | Führungsmittel für eine Vorrichtung zur Herstellung von Faservorformlingen im TFP-Verfahren für Verbundbauteile |
CN101267805A (zh) | 2005-07-27 | 2008-09-17 | 普洛体维生物治疗公司 | 制造脂质体的系统和方法 |
CN101253044B (zh) | 2005-08-31 | 2011-11-23 | 东丽株式会社 | 聚乳酸类树脂叠层片和其成型体 |
ATE439802T1 (de) | 2005-09-07 | 2009-09-15 | Koninkl Philips Electronics Nv | System und verfahren zum induktiven messen der bioimpedanz eines leitfähigen gewebes |
US20070065367A1 (en) | 2005-09-20 | 2007-03-22 | Rany Condos | Method of treating pulmonary disease with interferons |
KR100705981B1 (ko) | 2005-10-12 | 2007-04-10 | 주식회사 리제론 | 인간 성장호르몬을 포함하는 탈모방지 또는 발모촉진용조성물 |
US20070105756A1 (en) | 2005-10-31 | 2007-05-10 | May Thomas B | Vancomycin formulations having reduced amount of histamine |
DE102006051512A1 (de) | 2005-12-06 | 2007-06-14 | Pari GmbH Spezialisten für effektive Inhalation | Pharmazeutische Medikamentenzusammensetzungen mit Cyclosporin |
US8226975B2 (en) | 2005-12-08 | 2012-07-24 | Insmed Incorporated | Lipid-based compositions of antiinfectives for treating pulmonary infections and methods of use thereof |
DE102006001113B3 (de) | 2006-01-09 | 2007-06-28 | Pari GmbH Spezialisten für effektive Inhalation | Aerosoltherapievorrichtung |
US8263645B2 (en) | 2006-02-03 | 2012-09-11 | Pari Pharma Gmbh | Disodium cromoglycate compositions and methods for administering same |
DE102006006183A1 (de) | 2006-02-10 | 2007-08-16 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung für die Anwendung bei Frühgeborenen und Kleinkindern |
US7958887B2 (en) | 2006-03-10 | 2011-06-14 | Aradigm Corporation | Nozzle pore configuration for intrapulmonary delivery of aerosolized formulations |
DE102006012174A1 (de) | 2006-03-16 | 2007-09-20 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapiegerätekompressor |
EP2012750B1 (en) | 2006-04-06 | 2018-02-21 | Insmed Incorporated | Methods for coacervation induced liposomal encapsulation and formulations thereof |
DE102006017002B3 (de) | 2006-04-11 | 2007-01-11 | Pari GmbH Spezialisten für effektive Inhalation | Inhalationstherapievorrichtung mit mehrfachen Düsen |
USD583928S1 (en) | 2006-04-27 | 2008-12-30 | Pari Pharama Gmbh | Nebulizer |
WO2008039989A2 (en) | 2006-09-28 | 2008-04-03 | Transave, Inc. | Formulations of dnase and methods of use thereof |
US8071127B2 (en) | 2006-10-24 | 2011-12-06 | Aradigm Corporation | Dual action, inhaled formulations providing both an immediate and sustained release profile |
US8268347B1 (en) | 2006-10-24 | 2012-09-18 | Aradigm Corporation | Dual action, inhaled formulations providing both an immediate and sustained release profile |
US8119156B2 (en) | 2006-10-24 | 2012-02-21 | Aradigm Corporation | Dual action, inhaled formulations providing both an immediate and sustained release profile |
US20080108104A1 (en) | 2006-11-02 | 2008-05-08 | Colorado State University Research Foundation | Identification of bacterial species and subspecies using lipids |
EP1927373B1 (en) | 2006-11-30 | 2012-08-22 | PARI Pharma GmbH | Inhalation nebulizer |
WO2008098196A1 (en) * | 2007-02-09 | 2008-08-14 | United Therapeutics Corporation | Treprostinil treatment for interstitial lung disease and asthma |
EP1980285B1 (de) | 2007-04-11 | 2009-11-18 | PARI GmbH Spezialisten für effektive Inhalation | Aerosoltherapievorrichtung |
US20100196455A1 (en) | 2007-05-04 | 2010-08-05 | Transave, Inc. | Compositions of Multicationic Drugs for Reducing Interactions with Polyanionic Biomolecules and Methods of Use Thereof |
US9119783B2 (en) | 2007-05-07 | 2015-09-01 | Insmed Incorporated | Method of treating pulmonary disorders with liposomal amikacin formulations |
US9333214B2 (en) | 2007-05-07 | 2016-05-10 | Insmed Incorporated | Method for treating pulmonary disorders with liposomal amikacin formulations |
WO2008137917A1 (en) | 2007-05-07 | 2008-11-13 | Transave, Inc. | Method of treating bacterial infections with antibacterial formulations |
UA27298U (en) | 2007-06-13 | 2007-10-25 | Method for preventing pleural empyema after pneumonectomy | |
UA27804U (en) | 2007-07-26 | 2007-11-12 | Method for preventing respiratory complications after surgery in lungs and pleura | |
EP2030644A1 (en) | 2007-08-31 | 2009-03-04 | PARI Pharma GmbH | Aerosols for sinunasal drug delivery |
NZ562236A (en) * | 2007-10-05 | 2010-04-30 | Univ Otago | Detection of volatile compounds as markers for Mycobacteria tuberculosis |
US20090105126A1 (en) | 2007-10-23 | 2009-04-23 | Xingong Li | Methods of Treating Pulmonary Disorders using Liposomal Vancomycin Formulations |
KR101303180B1 (ko) | 2007-11-09 | 2013-09-09 | 삼성전자주식회사 | 수직채널 트랜지스터를 구비한 반도체 메모리 소자 및 그제조 방법 |
DE102007056462B4 (de) | 2007-11-23 | 2011-10-27 | Pari Pharma Gmbh | Einwegampulle für eine Vorrichtung zur Erzeugung von Aerosolen |
EP2278989B1 (en) | 2008-04-08 | 2021-05-26 | Melinta Therapeutics, Inc. | Oritavancin for inhibiting and treating biofilms |
DE102008022987A1 (de) | 2008-05-09 | 2009-11-12 | Pari Pharma Gmbh | Vernebler für Beatmungsmaschinen und Beatmungsmaschine mit einem solchen Vernebler |
CA2740000C (en) | 2008-10-09 | 2017-12-12 | Tekmira Pharmaceuticals Corporation | Improved amino lipids and methods for the delivery of nucleic acids |
EP2410985A2 (en) | 2009-03-26 | 2012-02-01 | Pulmatrix, Inc. | Methods for treating and preventing pneumonia and ventilator-associated tracheobronchitis |
EP2248517B1 (en) | 2009-05-08 | 2014-03-26 | PARI Pharma GmbH | Concentrated mast cell stabilizing pharmaceutical formulations |
DE102009026636B4 (de) | 2009-06-02 | 2011-04-14 | Pari Pharma Gmbh | Verfahren zum Verschweißen einer Membran mit einem Träger bei der Herstellung eines Membranverneblers |
EP2453962B1 (en) | 2009-07-17 | 2018-03-14 | Nektar Therapeutics | Negatively biased sealed nebulizers systems and methods |
PT2453864T (pt) | 2009-07-17 | 2016-12-22 | Nektar Therapeutics | Sistemas e métodos para acionamento de nebulizadores selados |
CN102472648B (zh) | 2009-07-22 | 2014-04-16 | 皇家飞利浦电子股份有限公司 | 具有低响应时间和高灵敏度的热流量传感器集成电路 |
US20130034534A1 (en) | 2009-09-29 | 2013-02-07 | Philipp Kroneberg | Method for treatment of patients with cystic fibrosis |
WO2011049960A2 (en) | 2009-10-21 | 2011-04-28 | Otonomy, Inc. | Compositions and methods for the treatment of sinonasal disorders |
US8536220B2 (en) | 2010-01-26 | 2013-09-17 | Murray Fulgham | Supplement composition and method of use |
WO2011108955A1 (en) | 2010-03-03 | 2011-09-09 | Universidade De Coimbra | Multi -targeting system comprising a nanocarrier, nucleic acid(s) and non-nucleic acid based drug(s) |
US9168225B2 (en) | 2010-04-23 | 2015-10-27 | The Board Of Trustees Of The University Of Illinois | Nano-hybrid delivery system for sequential utilization of passive and active targeting |
EP3456827A3 (en) | 2010-06-02 | 2019-05-08 | Alnylam Pharmaceuticals, Inc. | Compositions and methods directed to treating liver fibrosis |
EP2593110B1 (en) | 2010-07-12 | 2021-01-06 | Xellia Pharmaceuticals ApS | Treatment of lung infections by administration of tobramycin by aerolisation |
AU2010359346B2 (en) | 2010-08-20 | 2015-01-29 | Dr. Reddy's Laboratories Sa | Phospholipid depot |
WO2012047674A2 (en) * | 2010-09-27 | 2012-04-12 | Microdose Therapeutx, Inc. | Methods and compositions for disease treatment using inhalation |
ES2899621T3 (es) | 2010-09-29 | 2022-03-14 | Pulmatrix Operating Co Inc | Polvos secos catiónicos que comprenden sal de magnesio |
EP2457609A1 (en) | 2010-11-24 | 2012-05-30 | PARI Pharma GmbH | Aerosol generator |
LT2670242T (lt) | 2011-01-31 | 2022-06-27 | Avalyn Pharma Inc. | Aerozoliniai pirfenidono ir piridono anologų junginiai, ir jų panaudojimas |
CA2836643C (en) | 2011-05-19 | 2017-11-14 | Savara, Inc. | Dry powder vancomycin compositions and associated methods |
EP2717951B1 (en) | 2011-06-08 | 2020-10-28 | PARI Pharma GmbH | Aerosol generator |
DK2768958T3 (da) | 2011-10-18 | 2019-09-16 | Dicerna Pharmaceuticals Inc | Kationiske aminlipider og anvendelser deraf |
US20140308304A1 (en) | 2011-12-07 | 2014-10-16 | Alnylam Pharmaceuticals, Inc. | Lipids for the delivery of active agents |
EP2793860A1 (en) | 2011-12-22 | 2014-10-29 | Nuvo Research GmbH | Liposomal chlorite or chlorate compositions |
US20130280174A1 (en) | 2012-04-20 | 2013-10-24 | The Gillette Company | Personal care composition comprising metathesized unsaturated polyol esters |
US9925295B2 (en) | 2012-05-09 | 2018-03-27 | Amedica Corporation | Ceramic and/or glass materials and related methods |
CA2925687A1 (en) | 2012-09-27 | 2014-04-03 | The University Of North Carolina At Chapel Hill | Lipid coated nanoparticles containing agents having low aqueous and lipid solubilities and methods thereof |
EP2925298B1 (en) | 2012-11-29 | 2019-05-29 | Insmed Incorporated | Stabilized vancomycin formulations |
WO2015017807A1 (en) | 2013-08-01 | 2015-02-05 | University Of Georgia Research Foundation, Inc. | Liposomal formulations for the treatment of bacterial infections |
US9198359B2 (en) | 2013-09-20 | 2015-12-01 | Deere & Company | Frame for a reciprocating sieve |
AU2014340568B2 (en) | 2013-10-22 | 2017-02-02 | Aradigm Corporation | Inhaled surfactant-modified liposomal formulations providing both an immediate and sustained release profile |
US20160120806A1 (en) | 2014-04-08 | 2016-05-05 | Aradigm Corporation | Nanocrystals formed in a microenvironment |
EP3129008A4 (en) | 2014-04-08 | 2017-09-06 | Aradigm Corporation | Liposomes that form drug nanocrystals after freeze-thaw |
EP3129004A4 (en) | 2014-04-08 | 2017-11-15 | Aradigm Corporation | Liposomal ciprofloxacin formulations with activity against non-tuberculous mycobacteria |
US10195550B2 (en) | 2014-08-29 | 2019-02-05 | Emd Millipore Corporation | Single pass tangential flow filtration systems and tangential flow filtration systems with recirculation of retentate |
CN113171694B (zh) | 2015-03-19 | 2023-04-18 | 康涅狄格大学 | 用于连续制造脂质体药物制剂的系统和方法 |
CA2989884A1 (en) | 2015-07-09 | 2017-01-12 | Insmed Incorporated | Compositions and methods for treating lung diseases and lung injury |
JP2019500318A (ja) | 2015-11-18 | 2019-01-10 | インスメッド インコーポレイテッド | 細菌感染症を治療するための組成物及び方法 |
WO2019191627A1 (en) | 2018-03-30 | 2019-10-03 | Insmed Incorporated | Methods for continuous manufacture of liposomal drug products |
JP7449275B2 (ja) | 2018-05-02 | 2024-03-13 | インスメッド インコーポレイテッド | リポソーム薬物製剤の製造方法 |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012505265A (ja) * | 2008-10-13 | 2012-03-01 | インスメッド インコーポレイテッド | リポソームアミカシン処方物による肺疾患の治療方法 |
WO2013177226A1 (en) * | 2012-05-21 | 2013-11-28 | Insmed Incorporated | Systems for treating pulmonary infections |
WO2014025890A1 (en) * | 2012-08-10 | 2014-02-13 | University Of North Texas Health Science Center | Drug delivery vehicle comprising conjugates between targeting polyamino acids and fatty acids |
JP6646653B2 (ja) * | 2014-05-15 | 2020-02-14 | インスメッド インコーポレイテッド | 非結核性抗酸菌肺感染症を治療するための方法 |
Non-Patent Citations (1)
Title |
---|
INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 78, JPN6019002428, 1992, pages 227 - 235, ISSN: 0004418432 * |
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