JP5873013B2 - 2つ以上の活性剤を呼吸器送達するための組成物、方法および系 - Google Patents
2つ以上の活性剤を呼吸器送達するための組成物、方法および系 Download PDFInfo
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- JP5873013B2 JP5873013B2 JP2012513319A JP2012513319A JP5873013B2 JP 5873013 B2 JP5873013 B2 JP 5873013B2 JP 2012513319 A JP2012513319 A JP 2012513319A JP 2012513319 A JP2012513319 A JP 2012513319A JP 5873013 B2 JP5873013 B2 JP 5873013B2
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- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 claims description 8
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Description
特に具体的に定義しない限り、技術用語は、本明細書中で使用する場合、当技術分野で理解されるとおりのその通常の意味を有する。明確を期すために、以下の用語を具体的に定義する。
本明細書に記載の組成物は、2つ以上の活性剤を含み、懸濁媒体と、1種または複数種の活性剤粒子と、1種または複数種の懸濁粒子とを含む共懸濁剤である。当然ながら、必要に応じ、本明細書に記載の組成物は、1つまたは複数の追加成分を含んでもよい。さらに、本明細書に記載の組成物の成分の変形および組合せを使用してもよい。
本明細書に記載の組成物中に含まれる懸濁媒体は、1つまたは複数の噴射剤を含む。一般には、懸濁媒体としての使用に適した噴射剤は、室温での加圧下で液化でき、吸入または局所的な使用の際に安全で毒性学的に無害であるような噴射剤ガスである。加えて、選択される噴射剤は、懸濁粒子および活性剤粒子とあまり反応しないことが望ましい。例示的な適合性のある噴射剤としては、ヒドロフルオロアルカン(HFA)、過フッ化化合物(PFC)およびクロロフルオロカーボン(CFC)が挙げられる。
本明細書に記載の共懸濁剤中に含まれる活性剤粒子は、懸濁媒体内に分散および懸濁させることが可能であり、共懸濁剤からの呼吸可能な粒子の送達を容易にするようなサイズの物質から形成される。したがって、一実施形態では、活性剤粒子は、活性剤粒子の少なくとも90体積%が約7μm以下の光学直径を呈する微粉化された物質として供給される。他の実施形態では、活性剤粒子は、活性剤粒子の少なくとも90体積%が、約7μm〜約1μm、約5μm〜約2μm、および約3μm〜約2μmの範囲から選択される光学直径を呈する微粉化された物質として供給される。他の実施形態では、活性剤粒子は、活性剤粒子の少なくとも90体積%が、6μm以下、5μm以下、4μm以下または3μm以下から選択される光学直径を呈する微粉化された物質として供給される。別の実施形態では、活性剤粒子は、活性剤粒子物質の少なくとも50体積%が約4μm以下の光学直径を呈する微粉化された物質として供給される。さらなる実施形態では、活性剤粒子は、活性剤粒子物質の少なくとも50体積%が、約3μm以下、約2μm以下、約1.5μm以下および約1μm以下から選択される光学直径を呈する微粉化された物質として供給される。またさらなる実施形態では、活性剤粒子は、活性剤粒子の少なくとも50体積%が、約4μm〜約1μm、約3μm〜約1μm、約2μm〜約1μm、約1.3μmおよび約1.9μmの範囲から選択される光学直径を呈する微粉化された物質として供給される。
本明細書に記載の共懸濁剤組成物中に含まれる懸濁粒子は、該組成物中に含まれる活性剤の安定化および送達を容易にするように機能する。多様な形態の懸濁粒子を使用してもよいが、懸濁粒子は、典型的には、吸入にとって許容でき、選択される噴射剤中で実質的に不溶性の薬理学的に不活性な物質から形成される。一般的に、大多数の懸濁粒子は、呼吸可能な範囲内のサイズになっている。したがって、特定の実施形態では、懸濁粒子のMMADは、約10μmを超えないであろうが、約500nmを下回らない。代替的な一実施形態では、懸濁粒子のMMADは約5μm〜約750nmである。また別の実施形態では、懸濁粒子のMMADは約1μm〜約3μmである。MDIからの経鼻送達のための一実施形態で使用される場合、懸濁粒子のMMADは10μm〜50μmである。
本明細書中で提供される方法に関して記載するように、本明細書中で開示する共懸濁剤組成物はMDI系において使用してもよい。MDIは、エアロゾル形態の特定の量の医薬を送達するように構成される。一実施形態では、MDI系は、マウスピースと共に形成された作動装置中に配置された、加圧された液相製剤の充填された缶を備える。MDI系は、懸濁媒体と、少なくとも1種の活性剤粒子と、少なくとも1種の懸濁粒子とを含む本明細書に記載の製剤を含んでもよい。MDIにおいて使用される缶は、任意の適当な構成のものであってもよく、例示的な一実施形態では、缶の体積は、約5mL〜約25mLの範囲(たとえば、19mLの体積を有する缶など)であってもよい。器具を振った後、マウスピースを患者の口の中(口唇と歯との間)に挿入する。患者は、典型的には、大きく息を吐き出して肺を空にしてから、カートリッジを作動させながらゆっくり深呼吸する。
本明細書中では、少なくとも2つの活性剤を呼吸器送達するための医薬組成物を製剤化する方法が提供される。一実施形態では、この方法は、懸濁媒体と、1種または複数種の活性剤粒子と、1種または複数種の懸濁粒子とを供給するステップ、および、そのような成分を組み合わせて、活性剤粒子が懸濁粒子と会合して懸濁媒体内で懸濁粒子と同一場所に位置する組成物を形成することから本明細書に記載のとおりの共懸濁剤が形成されるステップを含む。そのような一実施形態では、活性剤粒子と懸濁粒子との会合は、噴射剤中での浮力が異なることからこれらの粒子が分離しないようなものである。理解されるであろうが、本明細書に記載のとおりの医薬組成物を製剤化する方法は、2種以上の活性剤粒子を1種または複数種の懸濁粒子と組み合わせて供給することを含むことができる。さらなる実施形態では、この方法は、2種以上の懸濁粒子を、結果として共懸濁剤が得られる方式で2種以上の活性剤粒子と組み合わせて供給することを含んでもよい。さらに他の実施形態では、1種または複数種の活性剤粒子は、本明細書に記載のとおりの1種または複数種の懸濁粒子と組み合わせてもよい。特定の実施形態では、活性剤粒子中に含まれる活性剤物質は、LABA活性剤、LAMA活性剤またはコルチコステロイド活性剤のうち1つまたは複数から選択される。一定の実施形態では、活性剤粒子は、活性剤物質から本質的に成り、追加的な添加剤、アジュバント、安定化剤などを含まない。
本明細書に記載のとおりの例示的な共懸濁剤組成物を調製および評価した。この組成物には、グリコピロレート(GP)活性剤とフマル酸ホルモテロール(FF)活性剤との組合せを含ませた。GPは、微粉化した結晶性の活性剤粒子として噴射剤中に存在した。GPを、懸濁粒子を形成する物質内に配置されたFFを含んだ噴霧乾燥した懸濁粒子と共懸濁させた。これを達成するため、脂質ベースの懸濁粒子を製造するために使用される原料にFFを溶解した。
FF、GPまたは両方を含有するMDIを、FFおよびGPそれぞれについて1作動当たり目標濃度2.4μgおよび18μgで調製した。GP活性剤を微粉化したところ、実施例1に記載のようにレーザー回折により測定した場合、それぞれ、d10、d50、d90が得られ、スパンは0.6μm、1.7μm、3.6μmおよび1.9μmであった。FFは、噴霧乾燥した懸濁粒子中に組み込み、2%がFF、91.5%がDSPCおよび6.5%がCaCl2の組成で実施例1に記載のように調製した。GP、FFおよびGP+FFのMDIを、目標質量の活性剤粒子および懸濁粒子を体積19mLのフッ化エチレンポリマー(FEP)被覆したアルミニウム缶(Presspart、Blackburn、UK)中に計り入れることにより調製した。缶を50μlバルブ(#BK357、Bespak、King’s Lynn、UK)でクリンプシールし、バルブ軸を通した過圧により10.2gのHFA134a(1,1,1,2−テトラフルオロエタン)(Ineos Fluor、Lyndhurst、UK)を充填した。噴射剤の注入後、缶を15秒間超音波処理して、リストアクション振盪機で30分間撹拌した。缶に、0.3mmの開口部のあるポリプロピレン製作動装置(#BK636、Bespak、King’s Lynn、UK)を取り付けた。
グリコピロレートとフマル酸ホルモテロールとを含有する組合せ共懸濁剤の定量噴霧式吸入器の薬物動態および安全性を臨床試験において評価した。この臨床試験は、MDIにより投与された4つの吸入治療剤を評価するために用いられた、単一施設、ランダム化、二重盲検、単一用量、4期間、4治療剤のクロスオーバー試験であった。4つの治療剤には、フマル酸ホルモテロール(FF)吸入エアロゾル剤、グリコピロレート(GP)吸入エアロゾル剤、GP+FF吸入エアロゾル剤、および、GP吸入エアロゾル剤に次いで直ちにFF吸入エアロゾル剤の送達を行う連続送達を含めた。GP+FF吸入エアロゾル剤、ならびにFF吸入エアロゾル剤およびGP吸入エアロゾル剤は、実施例2に記載のとおりに調製した。さらに、GP+FF吸入エアロゾル剤は、「固定」の組合せのGPおよびFFと名付け、GP吸入エアロゾル剤に次いで直ちにFF吸入エアロゾル剤の送達を行う連続送達を必要とする治療剤は、「ゆるい」組合せと名付けた。
本記載による例示的な2剤型共懸濁剤組成物を作製し、該組成物を組み込んでいる定量噴霧式吸入器を調製した。該組成物には、グリコピロレート(GP)とフマル酸ホルモテロール(FF)との組合せを含ませ、それぞれは、微粉化された結晶性の物質として供給された。組合せの結晶性の共懸濁剤MDIを半自動の懸濁剤充填により製造した。この2剤型共懸濁剤は、HFA134a噴射剤中で懸濁粒子と共懸濁させた2つの微結晶性の活性医薬原料(「APIs」、または単数形では「API」とも呼ぶ)であるGPとFFとの組合せから成っていた。2剤型共懸濁剤は、1作動当たり18μgのGPおよび1作動当たり4.8μgのFFの送達用量を供給するように製剤化した。2剤型共懸濁剤組成物の調製においては、一定の組成物中では、使用したFF API物質は「粗い」として表示され、他の組成物中では、使用したFF API物質は「細かい」として表示された。共懸濁剤組成物に組み込まれたのが粗いFFであるか細かいFFであるかによらず、該組成物は、1作動当たり4.8μgの送達FF用量を供給するように製剤化した。この実施例で記載した共懸濁剤組成物の製剤において使用した粗いFF、細かいFFおよびGP API物質の粒子サイズ特徴は、表2に詳細を記載してある。2剤型共懸濁剤組成物に加え、FF活性剤物質のみを組み込んでいる単剤療法型共懸濁剤組成物を製剤化した。このFF単剤療法型共懸濁剤は、粗いFF APIを利用した。当該FF単剤療法型共懸濁剤を使用して単剤療法型MDIを製造し、このFF単剤療法型MDIを、1作動当たり送達用量4.8μgのFFを供給するように製剤化および製造した。
キシナホ酸サルメテロール(SX)活性剤粒子とプロピオン酸フルチカゾン(FP)活性剤粒子との2剤型共懸濁剤組成物の製剤について説明する。FPおよびSXは両方とも、微粉化された結晶性の粒子として噴射剤中に存在する。この2種の微粉化された活性剤粒子を、噴霧乾燥された懸濁粒子と共懸濁させる。
キシナホ酸サルメテロール(SX)活性剤粒子とプロピオン酸フルチカゾン(FP)懸濁粒子との組合せ共懸濁剤組成物の製剤について説明する。SXは、微粉化された結晶性の粒子として噴射剤中に存在する。SXを、該懸濁粒子を形成する物質中に配置された微粉化されたFPを有する噴霧乾燥された懸濁粒子と共懸濁させる。これを達成するために、FP結晶は、脂質ベースの懸濁粒子を製造するために使用される供給原料中に懸濁させる。この実施例で参照される、活性剤粒子および懸濁粒子を形成するために使用するFPおよびSXは、実施例5に記載のとおりであった。
ブデソニド活性剤粒子とフロ酸モメタゾン活性剤粒子とを含む2剤型共懸濁剤組成物の製剤について説明する。ブデソニド(BD)およびフロ酸モメタゾン(MF)は、微粉化された結晶性の粒子として噴射剤中に存在し、噴霧乾燥された懸濁粒子と共懸濁させる。
フロ酸モメタゾン(MF)またはブデソニド(BD)のいずれかを含む懸濁粒子を用いて2剤型共懸濁剤組成物を調製し、この組成物を組み込んでいるMDIを調製した。この共懸濁剤組成物は、結晶性のグリコピロレート(GP)活性剤粒子およびフマル酸ホルモテロール(FF)活性剤粒子の組合せを含んでおり、MFまたはBDのいずれかを含む懸濁粒子と共懸濁させた。各APIは、微粉化された、結晶性の物質として供給された。
本記載による3剤型共懸濁剤組成物を作製し、該組成物を組み込んでいるMDIを調製した。この組成物は、グリコピロレート(GP)活性剤粒子と、フマル酸ホルモテロール(FF)活性剤粒子とフロ酸モメタゾン(MF)活性剤粒子との組合せを含んでおり、それぞれが、微粉化された結晶性のAPI物質として供給されていた。
本記載による例示的な3剤型共懸濁剤組成物を作製し、該組成物中に組み込まれている定量噴霧式吸入器を調製した。該3剤型共懸濁剤は、グリコピロレート(GP)または臭化チオトロピウム(TB)を、フマル酸ホルモテロール(FF)活性剤とフロ酸モメタゾン(MF)活性剤との組合せで含んでおり、各APIは、微粉化された結晶性の物質として使用した。
本記載による例示的な2剤型共懸濁剤組成物を作製し、該2剤型共懸濁剤組成物を組み込んでいるMDIを調製した。該組成物は、グリコピロレート(GP)およびフマル酸ホルモテロール(FF)の組合せを含んでおり、それぞれは、表14に示すとおりの粒子サイズ分布を有する微粉化された結晶性の物質として供給された。微結晶性のGPおよびFF物質は2種の活性剤粒子を供給し、懸濁粒子は、実施例4に記載のように調製した。この実施例に記載した2剤型共懸濁剤の調製においては、GP活性剤粒子、FF活性剤粒子および懸濁粒子をHFA134a噴射剤中で合わせた。
Claims (47)
- 薬学的に許容できる噴射剤を含む懸濁媒体と、
少なくとも2つの異なる種の活性剤粒子であって、少なくとも2種の活性剤粒子は異なる活性剤を含み、第1の種の活性剤粒子はグリコピロレート、チオトロピウム、トロスピウム、アクリジニウムおよびダロトロピウム(その任意の薬学的に許容できる塩、エステル、異性体または溶媒和物を含む)から選択される活性剤を含み、第2の種の活性剤粒子はバンブテロール、クレンブテロール、ホルモテロール、サルメテロール、カルモテロール、およびインダカテロール(その任意の薬学的に許容できる塩、エステル、異性体または溶媒和物を含む)から選択される活性剤を含む活性剤粒子と、
1種または複数種の呼吸可能な懸濁粒子とを含み、
1種または複数種の呼吸可能な懸濁粒子のそれぞれは、懸濁媒体に対する溶解性が懸濁媒体100部当たり1部以下であり、リン脂質を含む乾燥有孔微細構造体を含み、懸濁粒子の全質量は活性剤粒子の全質量を超え、前記少なくとも2つの異なる種の活性剤粒子および1または複数種の懸濁粒子は懸濁剤中で同一場所に位置して共懸濁剤を形成する、
定量噴霧式吸入器から送達可能な医薬組成物。 - 少なくとも3つの異なる種の活性剤粒子を含み、前記少なくとも3つの種の活性剤粒子のそれぞれが、異なる活性剤を含み、第3の種の活性剤粒子がベクロメタゾン、ブデソニド、シクレソニド、フルニソリド、フルチカゾン、メチルプレドニゾロン、モメタゾン、プレドニゾンおよびトリアムシノロンから選択されるコルチコステロイド活性剤(その任意の薬学的に許容できる塩、エステル、異性体または溶媒和物を含む)から選択される活性剤を含む、請求項1に記載の医薬組成物。
- 前記活性剤粒子の少なくとも50体積%が5μm以下の光学直径を呈する、請求項1または2に記載の医薬組成物。
- 前記有孔微細構造体が、DSPC(1,2−ジステアロイル−sn−グリセロ−3−ホスホコリン)および塩化カルシウムを含む、請求項1に記載の医薬組成物。
- 前記懸濁粒子が、1mg/ml〜15mg/mlの濃度で前記懸濁媒体中に含まれる、請求項1に記載の医薬組成物。
- 前記少なくとも1種の懸濁粒子のそれぞれが、10μm〜500nmのMMADを呈する、請求項1に記載の医薬組成物。
- 前記少なくとも1種の懸濁粒子のそれぞれが、0.5μm〜15μmの光学直径体積中央値を呈する、請求項1に記載の医薬組成物。
- 前記噴射剤が、HFA噴射剤、PFC噴射剤およびそれらの組合せから選択される噴射剤を含み、懸濁媒体は追加成分を含まない、請求項1に記載の医薬組成物。
- 懸濁粒子の全質量対活性剤粒子の全質量の比率が、1〜200である、請求項1に記載の医薬組成物。
- 前記少なくとも1種の懸濁粒子の全質量対少なくとも1種の活性剤粒子の全質量の比率が、1を超え最大200である、請求項1に記載の医薬組成物。
- 前記懸濁粒子が、少なくとも1gの加速度から選択される加速度での遠心分離により増幅された浮力を受けたときでも前記活性剤粒子と同一場所に位置したままである、請求項1に記載の医薬組成物。
- 噴射剤はHFA噴射剤であり、
第1の種の活性剤粒子はグリコピロレート(その任意の薬学的に許容できる塩、エステル、異性体または溶媒和物を含む)を含み、かつ、
第2の種の活性剤粒子は前記定量噴霧式吸入器の1作動当たり2μg〜10μgのホルモテロール送達用量をもたらすのに十分な濃度で前記懸濁媒体中に懸濁させたホルモテロール(その任意の薬学的に許容できる塩、エステル、異性体または溶媒和物を含む)を含む、
請求項1に記載の医薬組成物。 - 前記懸濁粒子の全質量対前記第1および第2の種の活性剤粒子の全質量の比率が、10〜200である、請求項12に記載の医薬組成物。
- 噴射剤はHFA噴射剤であり、
第1の種の活性剤粒子はグリコピロレート(その任意の薬学的に許容できる塩、エステル、異性体または溶媒和物を含む)を含み、その少なくとも90体積%が7μmの光学直径を呈し、
第2の種の活性剤は前記定量噴霧式吸入器の1作動当たり2μg〜10μgのホルモテロール送達用量をもたらすのに十分な濃度で前記懸濁媒体中に懸濁させたホルモテロール(その任意の薬学的に許容できる塩、エステル、異性体または溶媒和物を含む)を含み、
さらに、ベクロメタゾン、ブデソニド、シクレソニド、フルニソリド、フルチカゾン、メチルプレドニゾロン、モメタゾン、プレドニゾンおよびトリアムシノロンから選択される結晶コルチコステロイド(その任意の薬学的に許容できる塩、エステル、異性体または溶媒和物を含む)を含む第3の種の活性剤粒子を含む、
請求項1に記載の医薬組成物。 - 前記懸濁粒子の全質量対第1、第2および第3の種の活性剤粒子の全質量の比率が、1を超え200までから選択される、請求項14に記載の医薬組成物。
- 定量噴霧式吸入器による患者へのLAMA活性剤とLABA活性剤との組合せの呼吸器送達に適した組成物を調製する方法であって、
薬学的に許容できるHFA噴射剤を含む懸濁媒体を供給するステップと、
グリコピロレート(その薬学的に許容できる塩、エステル、異性体または溶媒和物を包含する)を含む第1の種の活性剤粒子を供給するステップと、
ホルモテロール(その薬学的に許容できる塩、エステル、異性体または溶媒和物を包含する)を含む第2の種の活性剤粒子を供給するステップと、
複数の呼吸可能な懸濁粒子であって、リン脂質を含む乾燥有孔微細構造体を含む懸濁粒子を供給するステップと、
前記懸濁媒体、前記第1および第2の種の活性剤粒子、ならびに前記複数の呼吸可能な懸濁粒子を、前記第1および第2の種の活性剤粒子が前記懸濁粒子と懸濁媒体中で同一場所に位置して共懸濁剤を形成し、前記活性剤粒子中に含まれる前記活性剤のそれぞれについて、前記定量噴霧式吸入器から前記患者に送達した際に前記共懸濁剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数が、グリコピロレートまたはホルモテロールのうち1つのみを含む類似製剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数の±20%以内であるように組み合わせるステップと
を含む方法。 - 前記懸濁媒体、前記第1および第2の種の活性剤粒子、ならびに前記複数の呼吸可能な懸濁粒子を、前記第1および第2の種の活性剤粒子が前記懸濁粒子と懸濁媒体中で同一場所に位置して共懸濁剤を形成し、前記活性剤粒子中に含まれる前記活性剤のそれぞれについて、前記定量噴霧式吸入器から前記患者に送達した際に前記共懸濁剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数が、グリコピロレートまたはホルモテロールのうち1つのみを含む類似製剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数の±15%以内であるように組み合わせるステップを含む、請求項16に記載の方法。
- 前記懸濁媒体、前記第1および第2の種の活性剤粒子、ならびに前記複数の呼吸可能な懸濁粒子を、前記第1および第2の種の活性剤粒子が前記懸濁粒子と懸濁媒体中で同一場所に位置して共懸濁剤を形成し、前記活性剤粒子中に含まれる前記活性剤のそれぞれについて、前記定量噴霧式吸入器から前記患者に送達した際に前記共懸濁剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数が、グリコピロレートまたはホルモテロールのうち1つのみを含む類似製剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数の±10%以内であるように組み合わせるステップを含む、請求項16に記載の方法。
- ベクロメタゾン、ブデソニド、シクレソニド、フルニソリド、フルチカゾン、メチルプレドニゾロン、モメタゾン、プレドニゾンおよびトリアムシノロンから選択されるコルチコステロイド(その任意の薬学的に許容できる塩、エステル、異性体または溶媒和物を含む)を含む第3の種の活性剤粒子を供給するステップと、
前記懸濁媒体、前記第1、第2および第3の種の活性剤粒子、ならびに前記複数の呼吸可能な懸濁粒子を、前記第1、第2および第3の種の活性剤粒子が前記懸濁粒子と懸濁媒体中で同一場所に位置して共懸濁剤を形成し、前記活性剤粒子中に含まれる前記活性剤のそれぞれについて、前記定量噴霧式吸入器から前記患者に送達した際に前記共懸濁剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数が、グリコピロレート、ホルモテロールまたはコルチコステロイドのうち1つのみを含む類似製剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数の±20%以内であるように組み合わせるステップと
をさらに含む、請求項16に記載の方法。 - 前記懸濁媒体、前記第1、第2および第3の種の活性剤粒子、ならびに前記複数の呼吸可能な懸濁粒子を、前記第1、第2および第3の種の活性剤粒子が前記懸濁粒子と懸濁媒体中で同一場所に位置して共懸濁剤を形成し、前記活性剤粒子中に含まれる活性剤のそれぞれについて、前記定量噴霧式吸入器から前記患者に送達した際に前記共懸濁剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数が、グリコピロレートまたはホルモテロールのうち1つのみを含む類似製剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数の±15%以内であるように組み合わせるステップを含む、請求項19に記載の方法。
- 前記懸濁媒体、前記第1、第2および第3の種の活性剤粒子、ならびに前記複数の呼吸可能な懸濁粒子を、前記第1、第2および第3の種の活性剤粒子が前記懸濁粒子と懸濁媒体中で同一場所に位置して共懸濁剤を形成し、前記活性剤粒子中に含まれる前記活性剤のそれぞれについて、前記定量噴霧式吸入器から前記患者に送達した際に前記共懸濁剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数が、グリコピロレート、ホルモテロールまたはコルチコステロイドのうち1つのみを含む類似製剤により達成されるエアロゾル特性、粒子サイズ分布の特徴、送達用量均一性および経時血漿濃度のうち1つまたは複数の±10%以内であるように組み合わせるステップを含む、請求項19に記載の方法。
- 複数の呼吸可能な懸濁粒子が噴霧乾燥プロセスを用いて調製される、請求項12および14のいずれかに記載の医薬組成物。
- 複数の呼吸可能な懸濁粒子がDSPCおよび塩化カルシウムを含む、請求項12および14のいずれかに記載の医薬組成物。
- 複数の呼吸可能な懸濁粒子が1mg/ml〜15mg/mlの濃度で懸濁媒体中に含まれる、請求項12および14のいずれか一項に記載の医薬組成物。
- 組成物は炎症性または閉塞性の肺の疾患または状態の処置用に調製されている、請求項1〜15および22〜24のいずれか一項に記載の医薬組成物。
- 疾患または状態の処置用に調整されている医薬組成物であって、前記疾患または状態は、喘息、COPD、他の薬物療法の結果生じる気道過反応性の増悪、アレルギー性鼻炎、副鼻腔炎、肺血管収縮、炎症、アレルギー、呼吸障害、呼吸窮迫症候群、肺高血圧症、肺血管収縮、および嚢胞性線維症に伴う肺の炎症および閉塞から選択される、請求項1〜15および22〜24のいずれか一項に記載の医薬組成物。
- 炎症性または閉塞性の肺の疾患または状態を処置するための組成物を製造することを含む、請求項16〜21のいずれか一項に記載の方法。
- 疾患または状態を処置するための組成物を製造することを含む方法であって、前記疾患または状態は、喘息、COPD、他の薬物療法の結果生じる気道過反応性の増悪、アレルギー性鼻炎、副鼻腔炎、肺血管収縮、炎症、アレルギー、呼吸障害、呼吸窮迫症候群、肺高血圧症、肺血管収縮、および嚢胞性線維症に伴う肺の炎症および閉塞から選択される、請求項16〜21のいずれか一項に記載の方法。
- 請求項1〜11のいずれか一項に記載の医薬組成物であって、共懸濁剤が、フッ化物塩、塩化物塩、臭化物塩、ヨウ化物塩、硝酸塩、硫酸塩、リン酸塩、ギ酸塩、酢酸塩、トリフルオロ酢酸塩、プロピオン酸塩、ブチレート、乳酸塩、クエン酸塩、酒石酸塩、リンゴ酸塩、マレイン酸塩、コハク酸塩、安息香酸塩、p−クロロ安息香酸塩、ジフェニル酢酸塩若しくはトリフェニル酢酸塩、o−ヒドロキシ安息香酸塩、p−ヒドロキシ安息香酸塩、1−ヒドロキシナフタレン−2−カルボン酸塩、3−ヒドロキシナフタレン−2−カルボン酸塩、メタンスルホン酸塩およびベンゼンスルホン酸塩から選択される、グリコピロレートの薬学的に許容できる塩を含む活性剤粒子の1つを含んでなる、医薬組成物。
- 請求項29に記載の医薬組成物であって、グリコピロレートの薬学的に許容できる塩が、フッ化物塩、塩化物塩、臭化物塩およびヨウ化物塩から選択される、医薬組成物。
- 請求項30に記載の医薬組成物であって、グリコピロレートの薬学的に許容できる塩が、3−[(シクロペンチル−ヒドロキシフェニルアセチル)オキシ]−1,1−ジメチルピロリジニウムブロマイドである、医薬組成物。
- 請求項1〜11のいずれか一項に記載の医薬組成物であって、共懸濁剤が、ホルモテロールの薬学的に許容できる塩、エステルまたは異性体を含有する活性剤粒子の1つを含んでなる、医薬組成物。
- 請求項32に記載の医薬組成物であって、ホルモテロールの薬学的に許容できる塩、エステルまたは異性体が、塩酸塩、臭化水素酸塩、硫酸塩、リン酸塩、フマル酸塩、リンゴ酸塩、酢酸塩、乳酸塩、クエン酸塩、酒石酸塩、アスコルビン酸塩、コハク酸塩、グルタル酸塩、グルコン酸塩、トリカルバリル酸塩、オレイン酸塩、安息香酸塩、p−メトキシ安息香酸塩、サリチル酸塩、o−およびp−ヒドロキシ安息香酸塩、p−クロロ安息香酸塩、メタンスルホン酸塩、p−トルエンスルホン酸塩ならびに3−ヒドロキシ−2−ナフタレンカルボン酸塩から選択されるホルモテロールの塩である、医薬組成物。
- 請求項33に記載の医薬組成物であって、ホルモテロールの薬学的に許容できる塩、エステルまたは異性体が、ホルモテロールフマレートである、医薬組成物。
- 請求項12〜15のいずれか一項に記載の医薬組成物であって、第1の種の活性剤粒子が、フッ化物塩、塩化物塩、臭化物塩、ヨウ化物塩、硝酸塩、硫酸塩、リン酸塩、ギ酸塩、酢酸塩、トリフルオロ酢酸塩、プロピオン酸塩、ブチレート、乳酸塩、クエン酸塩、酒石酸塩、リンゴ酸塩、マレイン酸塩、コハク酸塩、安息香酸塩、p−クロロ安息香酸塩、ジフェニル酢酸塩若しくはトリフェニル酢酸塩、o−ヒドロキシ安息香酸塩、p−ヒドロキシ安息香酸塩、1−ヒドロキシナフタレン−2−カルボン酸塩、3−ヒドロキシナフタレン−2−カルボン酸塩、メタンスルホン酸塩およびベンゼンスルホン酸塩から選択されるグリコピロレートの薬学的に許容できる塩を含む、医薬組成物。
- 請求項35に記載の医薬組成物であって、グリコピロレートの薬学的に許容できる塩が、フッ化物塩、塩化物塩、臭化物塩およびヨウ化物塩から選択される、医薬組成物。
- 請求項36に記載の医薬組成物であって、グリコピロレートの薬学的に許容できる塩が、3−[(シクロペンチル−ヒドロキシフェニルアセチル)オキシ]−1,1−ジメチルピロリジニウムブロマイドである、医薬組成物。
- 請求項12〜15および35〜37のいずれか一項に記載の医薬組成物であって、第2の種の活性薬剤が、塩酸塩、臭化水素酸塩、硫酸塩、リン酸塩、フマル酸塩、リンゴ酸塩、酢酸塩、乳酸塩、クエン酸塩、酒石酸塩、アスコルビン酸塩、コハク酸塩、グルタル酸塩、グルコン酸塩、トリカルバリル酸塩、オレイン酸塩、安息香酸塩、p−メトキシ安息香酸塩、サリチル酸塩、o−およびp−ヒドロキシ安息香酸塩、p−クロロ安息香酸塩、メタンスルホン酸塩、p−トルエンスルホン酸塩ならびに3−ヒドロキシ−2−ナフタレンカルボン酸塩から選択されるホルモテロールの塩を含む、医薬組成物。
- 請求項38に記載の医薬組成物であって、ホルモテロールの薬学的に許容できる塩、エステルまたは異性体が、ホルモテロールフマレートである、医薬組成物。
- 請求項1〜15および29のいずれか一項に記載の医薬組成物であって、異なる2種の活性剤粒子の少なくとも一つが、結晶活性剤の呼吸可能な粒子を含む、医薬組成物。
- 請求項40に記載の医薬組成物であって、活性剤の各々の種が、結晶活性剤の呼吸可能な粒子を含む、医薬組成物。
- 請求項1〜14、24、25および29〜40のいずれか一項に記載の医薬組成物を含む缶を含み、炎症性または閉塞性の肺の疾患または状態の処置用に調製されている、定量噴霧式吸入器。
- 疾患または状態の処置用に調整されている医薬組成物であって、前記疾患または状態は、喘息、COPD、他の薬物療法の結果生じる気道過反応性の増悪、アレルギー性鼻炎、副鼻腔炎、肺血管収縮、炎症、アレルギー、呼吸障害、呼吸窮迫症候群、肺高血圧症、肺血管収縮、および嚢胞性線維症に伴う肺の炎症および閉塞から選択される、請求項1〜14、24、25および29〜40のいずれか一項に記載の医薬組成物を含む、定量噴霧式吸入器。
- 定量噴霧式吸入器の作動により、2つ以上の活性剤が、缶が空になるまで、±25%またはより良好なDDUで同時に送達される、請求項43に記載の定量噴霧式吸入器。
- 定量噴霧式吸入器の作動により放出されるエアロゾルの微細粒子分率が、缶が空になるまで最初の微細粒子分率の80%以内に維持される、請求項44に記載の定量噴霧式吸入器。
- 定量噴霧式吸入器の作動により放出されるエアロゾルの微細粒子分率が、缶が空になるまで最初の微細粒子分率の90%以内に維持される、請求項44に記載の定量噴霧式吸入器。
- 定量噴霧式吸入器の作動により放出されるエアロゾルの微細粒子分率が、缶が空になるまで最初の微細粒子分率の95%以内に維持される、請求項44に記載の定量噴霧式吸入器。
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Families Citing this family (70)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1894591B1 (en) | 2002-03-20 | 2013-06-26 | MannKind Corporation | Cartridge for an inhalation apparatus |
DK1786784T3 (da) | 2004-08-20 | 2011-02-14 | Mannkind Corp | Katalyse af diketopiperazinsyntese |
CN104436170B (zh) | 2004-08-23 | 2018-02-23 | 曼金德公司 | 用于药物输送的二酮哌嗪盐 |
US10002325B2 (en) | 2005-03-30 | 2018-06-19 | Primal Fusion Inc. | Knowledge representation systems and methods incorporating inference rules |
HUE028623T2 (en) | 2005-09-14 | 2016-12-28 | Mannkind Corp | Active substance formulation method based on increasing the affinity of the active ingredient for binding to the surface of crystalline microparticles |
IN2015DN00888A (ja) | 2006-02-22 | 2015-07-10 | Mannkind Corp | |
ES2570400T3 (es) | 2008-06-13 | 2016-05-18 | Mannkind Corp | Un inhalador de polvo seco y un sistema para el suministro de fármacos |
US8485180B2 (en) | 2008-06-13 | 2013-07-16 | Mannkind Corporation | Dry powder drug delivery system |
JP5479465B2 (ja) | 2008-06-20 | 2014-04-23 | マンカインド コーポレイション | 吸入努力をリアルタイムにプロファイルする対話式機器および方法 |
US8314106B2 (en) | 2008-12-29 | 2012-11-20 | Mannkind Corporation | Substituted diketopiperazine analogs for use as drug delivery agents |
US8815258B2 (en) * | 2009-05-29 | 2014-08-26 | Pearl Therapeutics, Inc. | Compositions, methods and systems for respiratory delivery of two or more active agents |
AU2010253776B2 (en) * | 2009-05-29 | 2015-01-22 | Pearl Therapeutics, Inc. | Compositions for pulmonary delivery of long-acting muscarinic antagonists and long-acting B2 adrenergic receptor agonists and associated methods and systems |
MX359281B (es) * | 2010-06-21 | 2018-09-21 | Mannkind Corp | Sistema y metodos para suministrar un farmaco en polvo seco. |
US10474647B2 (en) | 2010-06-22 | 2019-11-12 | Primal Fusion Inc. | Methods and devices for customizing knowledge representation systems |
MX353285B (es) | 2011-04-01 | 2018-01-05 | Mannkind Corp | Paquete de blister para cartuchos farmaceuticos. |
SG194896A1 (en) * | 2011-05-17 | 2013-12-30 | Pearl Therapeutics Inc | Compositions, methods & systems for respiratory delivery of two or more active agents |
CN105106200A (zh) * | 2011-05-17 | 2015-12-02 | 珍珠治疗公司 | 用于呼吸递送两种或多种活性剂的组合物、方法和系统 |
WO2012174472A1 (en) | 2011-06-17 | 2012-12-20 | Mannkind Corporation | High capacity diketopiperazine microparticles |
GB201113662D0 (en) * | 2011-08-08 | 2011-09-21 | Prosonix Ltd | Pharmaceutical compositions |
CN103945859A (zh) | 2011-10-24 | 2014-07-23 | 曼金德公司 | 用于治疗疼痛的方法和组合物 |
EP2836204B1 (en) * | 2012-04-13 | 2020-07-08 | GlaxoSmithKline Intellectual Property Development Limited | Aggregate particles |
WO2014012069A2 (en) | 2012-07-12 | 2014-01-16 | Mannkind Corporation | Dry powder drug delivery systems and methods |
CN102872027B (zh) * | 2012-09-18 | 2014-03-12 | 刘晓忠 | 一种治疗肺部疾病的药物颗粒的制备和吸入式复方气雾剂的制备 |
CN104994854A (zh) * | 2013-01-28 | 2015-10-21 | 理森制药股份公司 | 通过吸入罗氟司特n-氧化物治疗自身免疫、呼吸和/或炎性病症的方法 |
US9682038B2 (en) * | 2013-01-31 | 2017-06-20 | Prosonix Limited | Pharmaceutical compositions comprising multi-component crystalline particles suitable for use in inhalation therapy |
GB201301721D0 (en) * | 2013-01-31 | 2013-03-20 | Prosonix Ltd | Pharmaceutical Preparations |
HUE050050T2 (hu) * | 2013-03-04 | 2020-11-30 | Besins Healthcare Lu Sarl | Hordozórészecskékhez kötõdõ hatóanyag nanorészecskéket tartalmazó száraz gyógyászati kompozíciók |
AU2014229361B2 (en) * | 2013-03-14 | 2016-08-04 | Novartis Ag | Deamorphization of spray-dried formulations via spray-blending |
WO2014144894A1 (en) * | 2013-03-15 | 2014-09-18 | Pearl Therapeutics, Inc. | Methods and systems for conditioning of particulate crystalline materials |
US11554229B2 (en) | 2013-03-26 | 2023-01-17 | OptiNose Inc. | Nasal administration |
CN105324106A (zh) | 2013-04-01 | 2016-02-10 | 普马特里克斯营业公司 | 噻托铵干粉 |
US9393202B2 (en) * | 2013-04-26 | 2016-07-19 | Chiesi Farmaceutici S.P.A | Particle size reduction of an antimuscarinic compound |
RU2015154720A (ru) * | 2013-05-22 | 2017-06-27 | Перл Терапьютикс, Инк. | Композиции, способы и системы для респираторной доставки трех или более активных средств |
KR102321339B1 (ko) | 2013-07-18 | 2021-11-02 | 맨카인드 코포레이션 | 열-안정성 건조 분말 약제학적 조성물 및 방법 |
DK3054920T3 (da) * | 2013-10-07 | 2021-03-29 | Teva Branded Pharmaceutical Products R&D Inc | Tørpulverinhalator |
MX2016006376A (es) * | 2013-11-22 | 2016-10-28 | Teva Branded Pharmaceutical Products R&D Inc | Un medicamento inhalable. |
GB201321717D0 (en) * | 2013-12-09 | 2014-01-22 | Pharmachemie Bv | Inhalable Medicaments |
GB201402556D0 (en) | 2014-02-13 | 2014-04-02 | Crystec Ltd | Improvements relating to inhalable particles |
US10307464B2 (en) | 2014-03-28 | 2019-06-04 | Mannkind Corporation | Use of ultrarapid acting insulin |
CN104188941B (zh) * | 2014-09-02 | 2016-11-16 | 重庆和平制药有限公司 | 一种制备盐酸克仑特罗吸入粉雾剂的方法 |
BR112017006778A2 (pt) * | 2014-10-01 | 2018-01-09 | Als Mountain Llc | composição farmacêutica que compreende aspirina, metformina e serotonina com tensoativo não iônico |
MA41378A (fr) * | 2015-01-20 | 2017-11-28 | Teva Branded Pharmaceutical Prod R & D Inc | Inhalateur de poudre sèche comprenant du propionate de fluticasone et du xinafoate de salmétérol |
US20160310410A1 (en) | 2015-04-24 | 2016-10-27 | Glenmark Specialty S.A. | Pharmaceutical compositions comprising arformoterol and glycopyrronium |
WO2017108917A1 (en) | 2015-12-22 | 2017-06-29 | Astrazeneca Ab | Pharmaceutical compositions for use in the treatment of chronic obstructive pulmonary disease |
WO2017157265A1 (zh) * | 2016-03-15 | 2017-09-21 | 广东东阳光药业有限公司 | 喷雾剂、喷雾装置以及喷雾组件 |
WO2017201003A1 (en) * | 2016-05-17 | 2017-11-23 | Mayo Foundation For Medical Education And Research | Materials and methods for treating chronic cough |
WO2018002779A1 (en) | 2016-06-30 | 2018-01-04 | Philip Morris Products S.A. | Nicotine particles |
ES2957459T3 (es) | 2016-09-19 | 2024-01-19 | Mexichem Fluor Sa De Cv | Composición farmacéutica que comprende glicopirrolato |
JP6906947B2 (ja) * | 2016-12-22 | 2021-07-21 | キヤノン株式会社 | 画像処理装置、撮像装置、画像処理方法およびコンピュータのプログラム |
CN106943350A (zh) * | 2017-03-14 | 2017-07-14 | 上海现代药物制剂工程研究中心有限公司 | 含毒蕈碱受体拮抗剂和β2受体激动剂的气雾剂及制备方法 |
CN107243080B (zh) * | 2017-06-21 | 2021-11-12 | 上海上药信谊药厂有限公司 | 一种吸入式气雾剂、其原料组合物及制备方法 |
IL273713B2 (en) * | 2017-10-09 | 2023-10-01 | Pearl Therapeutics Inc | Drug administration systems and related methods |
JP7372727B2 (ja) | 2017-11-20 | 2023-11-01 | 三菱重工業株式会社 | 系統運用者側コンピュータ、発電事業者側コンピュータ、電力システム、制御方法及びプログラム |
JP7090941B2 (ja) * | 2018-10-02 | 2022-06-27 | 学校法人 名城大学 | 吸入粉末剤、その評価方法及びその用途 |
CN109632555B (zh) * | 2018-12-28 | 2021-07-27 | 上海新黄河制药有限公司 | 一种富马酸福莫特罗无定型含量的动态蒸汽吸附分析方法 |
WO2020229966A1 (en) * | 2019-05-10 | 2020-11-19 | Glenmark Pharmaceutical Limited | Stable aerosol composition for inhalation comprising glycopyrronium |
CN112137957B (zh) | 2019-06-26 | 2022-07-29 | 长风药业股份有限公司 | 一种药用吸入气雾剂及其制备方法 |
WO2020263994A1 (en) * | 2019-06-27 | 2020-12-30 | Cai Gu Huang | Inhalable formulation of a solution containing formoterol fumarate and aclidinium bromide |
CN112972384B (zh) * | 2019-12-02 | 2022-03-18 | 长风药业股份有限公司 | 一种格隆溴铵和茚达特罗原料药微粉混合物的制备方法 |
WO2021165348A1 (en) * | 2020-02-20 | 2021-08-26 | Chiesi Farmaceutici S.P.A. | Pressurised metered dose inhalers comprising a buffered pharmaceutical formulation |
ES2929818T3 (es) * | 2020-05-18 | 2022-12-02 | Orexo Ab | Nueva composición farmacéutica para la administración de fármacos |
US20220000767A1 (en) * | 2020-07-06 | 2022-01-06 | Sensory Cloud, Inc. | Nasal hygiene compositions, antimicrobial treatments, devices, and articles for delivery of same to the nose, trachea and main bronchi |
WO2022016068A1 (en) * | 2020-07-16 | 2022-01-20 | Tbd Pharma Llc | Dexamethasone solution for the treatment of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infections |
TW202241410A (zh) * | 2021-01-08 | 2022-11-01 | 大陸商江蘇恒瑞醫藥股份有限公司 | 可經由定量吸入器遞送的藥物組合物 |
JP2024049405A (ja) * | 2021-02-22 | 2024-04-10 | 興和株式会社 | 新規吸入剤 |
MX2024000465A (es) | 2021-07-09 | 2024-04-05 | Astrazeneca Pharmaceuticals Lp | Composiciones, metodos y sistemas para la administracion de farmacos en aerosol. |
EP4236921A1 (en) | 2021-11-25 | 2023-09-06 | Orexo AB | Pharmaceutical composition comprising adrenaline |
CN118414148A (zh) | 2021-12-20 | 2024-07-30 | 阿斯利康(瑞典)有限公司 | 用于气溶胶药物递送的组合物、方法和系统 |
WO2023212191A1 (en) | 2022-04-28 | 2023-11-02 | Astrazeneca Ab | Combination of albuterol and budesonide for the treatment of asthma |
CN117357485B (zh) * | 2023-11-01 | 2024-09-24 | 山东京卫制药有限公司 | 一种改良的可吸入的载体颗粒及应用 |
Family Cites Families (176)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2956062A (en) * | 1959-02-26 | 1960-10-11 | Robins Co Inc A H | Esters of amino alcohols |
US3994974A (en) | 1972-02-05 | 1976-11-30 | Yamanouchi Pharmaceutical Co., Ltd. | α-Aminomethylbenzyl alcohol derivatives |
SE378109B (ja) * | 1972-05-19 | 1975-08-18 | Bofors Ab | |
US4187301A (en) | 1978-04-05 | 1980-02-05 | Syntex (U.S.A.) Inc. | 17 Beta-thiocarboxylic acid esters of 6 alpha, 6 beta-difluoro-3-oxoandrost-4-enes |
CA1201114A (en) * | 1980-02-15 | 1986-02-25 | Gordon H. Phillipps | Androstane carbothioates |
ATE8790T1 (de) * | 1981-02-02 | 1984-08-15 | Schering Corporation | Aromatische heterocyclische steroidester, verfahren zu ihrer herstellung und pharmazeutische zusammensetzungen, die sie enthalten. |
ZW6584A1 (en) | 1983-04-18 | 1985-04-17 | Glaxo Group Ltd | Phenethanolamine derivatives |
GB8432063D0 (en) | 1984-12-19 | 1985-01-30 | Riker Laboratories Inc | Physically modified steroids |
US5707634A (en) | 1988-10-05 | 1998-01-13 | Pharmacia & Upjohn Company | Finely divided solid crystalline powders via precipitation into an anti-solvent |
GB8903593D0 (en) | 1989-02-16 | 1989-04-05 | Pafra Ltd | Storage of materials |
IL95590A (en) | 1989-09-08 | 1996-06-18 | Glaxo Group Ltd | Medicinal preparations containing Salmetrol and Pluticasone Propionate |
CA2024872C (en) | 1989-09-08 | 2002-07-09 | James Barry Douglas Palmer | Medicaments |
DE3931041C2 (de) | 1989-09-16 | 2000-04-06 | Boehringer Ingelheim Kg | Ester von Thienylcarbonsäuren mit Aminoalkoholen, ihre Quaternierungsprodukte, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
US5610163A (en) | 1989-09-16 | 1997-03-11 | Boehringer Ingelheim Gmbh | Esters of thienyl carboxylic acids and amino alcohols and their quaternization products |
SG45171A1 (en) | 1990-03-21 | 1998-01-16 | Boehringer Ingelheim Int | Atomising devices and methods |
IE912999A1 (en) | 1990-09-07 | 1992-03-11 | Abbott Lab | Phenanthridine compounds |
CA2091360C (en) | 1990-09-10 | 1997-04-08 | Pui-Ho Yuen | Mometasone furoate monohydrate, process for making same and pharmaceutical compositions |
DE4108393A1 (de) | 1991-03-15 | 1992-09-17 | Boehringer Ingelheim Kg | Neue ester bi- und tricyclischer aminoalkohole, ihre herstellung und ihre verwendung in arzneimitteln |
US5635563A (en) | 1991-04-01 | 1997-06-03 | Tomoegawa Paper Co., Ltd. | Polyaniline derivatives and their production process |
SE9302777D0 (sv) * | 1993-08-27 | 1993-08-27 | Astra Ab | Process for conditioning substances |
AU659645B2 (en) | 1991-06-26 | 1995-05-25 | Inhale Therapeutic Systems | Storage of materials |
WO1993011773A1 (en) | 1991-12-18 | 1993-06-24 | Aktiebolaget Astra | New combination of formoterol and budesonide |
US6582728B1 (en) | 1992-07-08 | 2003-06-24 | Inhale Therapeutic Systems, Inc. | Spray drying of macromolecules to produce inhaleable dry powders |
US5849263A (en) | 1993-03-30 | 1998-12-15 | Charlotte-Mecklenburg Hospital Authority | Pharmaceutical compositions containing alkylaryl polyether alcohol polymer |
GB9313642D0 (en) | 1993-07-01 | 1993-08-18 | Glaxo Group Ltd | Method and apparatus for the formation of particles |
ATE233544T1 (de) | 1993-12-02 | 2003-03-15 | Abbott Lab | Aerosole als darreichungsform mit cfc-freiem treibmittel |
SE9404080L (sv) * | 1993-12-28 | 1995-06-29 | Ciba Geigy Ag | Förfarande för framställning av en optiskt ren enantiomer av formoterol |
US5837699A (en) | 1994-01-27 | 1998-11-17 | Schering Corporation | Use of mometasone furoate for treating upper airway passage diseases |
AU680727B2 (en) * | 1994-02-09 | 1997-08-07 | Kinerton Limited | Process for drying a material from solution |
GB9413202D0 (en) | 1994-06-30 | 1994-08-24 | Univ Bradford | Method and apparatus for the formation of particles |
DE4440337A1 (de) * | 1994-11-11 | 1996-05-15 | Dds Drug Delivery Services Ges | Pharmazeutische Nanosuspensionen zur Arzneistoffapplikation als Systeme mit erhöhter Sättigungslöslichkeit und Lösungsgeschwindigkeit |
EE9700138A (et) * | 1994-12-22 | 1997-12-15 | Astra Aktiebolag | Aerosoolravimvormid |
US5612053A (en) * | 1995-04-07 | 1997-03-18 | Edward Mendell Co., Inc. | Controlled release insufflation carrier for medicaments |
GB9507768D0 (en) | 1995-04-13 | 1995-05-31 | Glaxo Group Ltd | Method of apparatus |
ATE287703T1 (de) * | 1995-04-14 | 2005-02-15 | Nektar Therapeutics | Pulverförmige pharmazeutische formulierungen mit verbesserter dispergierbarkeit |
US6309671B1 (en) * | 1995-04-14 | 2001-10-30 | Inhale Therapeutic Systems | Stable glassy state powder formulations |
US6258341B1 (en) | 1995-04-14 | 2001-07-10 | Inhale Therapeutic Systems, Inc. | Stable glassy state powder formulations |
US5833891A (en) | 1996-10-09 | 1998-11-10 | The University Of Kansas | Methods for a particle precipitation and coating using near-critical and supercritical antisolvents |
DE19614421C2 (de) | 1996-04-12 | 1999-12-16 | Biovision Gmbh | Verfahren zur Herstellung eines biodegradierbaren Knochenersatz- und Implantatwerkstoffes und biodegradierbarer Knochenersatz- und Implantatwerkstoff |
GB9610821D0 (en) | 1996-05-23 | 1996-07-31 | Glaxo Wellcome Inc | Metering apparatus |
GB9612297D0 (en) * | 1996-06-11 | 1996-08-14 | Minnesota Mining & Mfg | Medicinal aerosol formulations |
US6054488A (en) * | 1996-06-11 | 2000-04-25 | 3M Innovative Properties Company | Medicinal aerosol formulations of formoterol |
US5886200A (en) | 1996-07-01 | 1999-03-23 | Schering Corporation | Process for the preparation of 17-esters of 9 α, 21-dihalo-pregnane-11 β, 17 α-diol-20-ones |
US6068832A (en) * | 1996-08-29 | 2000-05-30 | Schering Corporation | Chlorofluorocarbon-free mometasone furoate aerosol formulations |
SE9603669D0 (sv) | 1996-10-08 | 1996-10-08 | Astra Ab | New combination |
US6040344A (en) | 1996-11-11 | 2000-03-21 | Sepracor Inc. | Formoterol process |
DK0937041T3 (da) * | 1996-11-11 | 2003-08-11 | Christian R Noe | Anvendelse af et farmaceutisk egnet salt af (3R,2'R)-3-[(cyclopentil-hydroxyphenylacetyl)oxyl]-1,1-dimethyl-pyrrolidinium til fremstilling af et lægemiddel |
SE9700135D0 (sv) * | 1997-01-20 | 1997-01-20 | Astra Ab | New formulation |
ES2316681T3 (es) | 1997-03-20 | 2009-04-16 | Schering Corporation | Formas de dosificacion de aglomerados en polvo. |
US6129905A (en) * | 1997-04-21 | 2000-10-10 | Aeropharm Technology, Inc. | Aerosol formulations containing a sugar as a dispersant |
US6010935A (en) * | 1997-08-21 | 2000-01-04 | Micron Technology, Inc. | Self aligned contacts |
SE9703407D0 (sv) | 1997-09-19 | 1997-09-19 | Astra Ab | New use |
US20020017295A1 (en) | 2000-07-07 | 2002-02-14 | Weers Jeffry G. | Phospholipid-based powders for inhalation |
US6433040B1 (en) * | 1997-09-29 | 2002-08-13 | Inhale Therapeutic Systems, Inc. | Stabilized bioactive preparations and methods of use |
US20060165606A1 (en) * | 1997-09-29 | 2006-07-27 | Nektar Therapeutics | Pulmonary delivery particles comprising water insoluble or crystalline active agents |
US6565885B1 (en) * | 1997-09-29 | 2003-05-20 | Inhale Therapeutic Systems, Inc. | Methods of spray drying pharmaceutical compositions |
US6309623B1 (en) * | 1997-09-29 | 2001-10-30 | Inhale Therapeutic Systems, Inc. | Stabilized preparations for use in metered dose inhalers |
US6946117B1 (en) * | 1997-09-29 | 2005-09-20 | Nektar Therapeutics | Stabilized preparations for use in nebulizers |
IL135126A0 (en) | 1997-09-29 | 2001-05-20 | Inhale Therapeutic Syst | Perforated microparticles and methods of use and preparation thereof |
HUP0101733A3 (en) | 1998-03-05 | 2001-12-28 | Senju Pharma Co | Pharmaceutical compositions containing sulfonyl-dipeptides and their use |
SE9802073D0 (sv) | 1998-06-11 | 1998-06-11 | Astra Ab | New use |
US6260549B1 (en) * | 1998-06-18 | 2001-07-17 | Clavius Devices, Inc. | Breath-activated metered-dose inhaler |
US6451285B2 (en) * | 1998-06-19 | 2002-09-17 | Baker Norton Pharmaceuticals, Inc. | Suspension aerosol formulations containing formoterol fumarate and a fluoroalkane propellant |
WO2000006121A1 (de) | 1998-07-24 | 2000-02-10 | Jago Research Ag | Medizinische aerosolformulierungen |
WO2000007567A1 (de) * | 1998-08-04 | 2000-02-17 | Jago Research Ag | Medizinische aerosolformulierungen |
CZ303154B6 (cs) * | 1998-11-13 | 2012-05-09 | Jagotec Ag | Suchá prášková formulace k inhalaci obsahující stearát horecnatý |
GB9912639D0 (en) * | 1999-05-28 | 1999-07-28 | Britannia Pharmaceuticals Ltd | Improvements in and relating to treatment of respiratory conditions |
GB9826284D0 (en) | 1998-12-01 | 1999-01-20 | Rhone Poulence Rorer Limited | Process |
US6004537A (en) | 1998-12-18 | 1999-12-21 | Baker Norton Pharmaceuticals, Inc. | Pharmaceutical solution aerosol formulations containing fluoroalkanes, budesonide and formoterol |
CA2356637C (en) | 1998-12-22 | 2011-09-13 | The University Of North Carolina At Chapel Hill | Compounds and methods for the treatment of airway diseases and for the delivery of airway drugs |
GB9902689D0 (en) * | 1999-02-08 | 1999-03-31 | Novartis Ag | Organic compounds |
GB9903759D0 (en) * | 1999-02-18 | 1999-04-14 | Novartis Ag | Organic compounds |
GB9904919D0 (en) * | 1999-03-03 | 1999-04-28 | Novartis Ag | Organic compounds |
ATE363892T1 (de) | 1999-03-05 | 2007-06-15 | Chiesi Farma Spa | Verbesserte pulverformulierungen zur inhalation |
SE9900833D0 (sv) * | 1999-03-09 | 1999-03-09 | Astra Ab | Novel combination |
DE19921693A1 (de) * | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Neuartige Arzneimittelkompositionen auf der Basis von anticholinergisch wirksamen Verbindungen und ß-Mimetika |
ATE233084T1 (de) | 1999-04-14 | 2003-03-15 | Glaxo Group Ltd | Pharmazeutische aerosolformulierung |
US20100197719A1 (en) * | 1999-05-12 | 2010-08-05 | Boehringer Ingelheim Pharma Kg | Medicament compositions containing anticholinergically-effective compounds and betamimetics |
AU780327B2 (en) | 1999-06-30 | 2005-03-17 | Novartis Ag | Spray drying process for preparing dry powders |
ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
PT102343B (pt) * | 1999-08-02 | 2003-11-28 | Hovione Farmaciencia Sa | Processo para a preparacao de furoato mometasona |
US6586008B1 (en) * | 1999-08-25 | 2003-07-01 | Advanced Inhalation Research, Inc. | Use of simple amino acids to form porous particles during spray drying |
HU229310B1 (en) | 1999-10-29 | 2013-10-28 | Nektar Therapeutics | Dry powder compositions having improved dispersivity |
DE19961300A1 (de) | 1999-12-18 | 2001-06-21 | Asta Medica Ag | Vorratssystem für Arzneimittel in Pulverform und damit ausgestatteter Inhalator |
US6596261B1 (en) | 2000-01-25 | 2003-07-22 | Aeropharm Technology Incorporated | Method of administering a medicinal aerosol formulation |
IT1317846B1 (it) | 2000-02-22 | 2003-07-15 | Chiesi Farma Spa | Formulazioni contenenti un farmaco anticolinergico per il trattamentodella broncopneumopatia cronica ostruttiva. |
GB0008660D0 (en) | 2000-04-07 | 2000-05-31 | Arakis Ltd | The treatment of respiratory diseases |
WO2001078735A1 (en) | 2000-04-13 | 2001-10-25 | Innovata Biomed Limited | Medicaments for treating respiratory disorders comprising formoterol and fluticasone |
WO2001085136A2 (en) * | 2000-05-10 | 2001-11-15 | Alliance Pharmaceutical Corporation | Phospholipid-based powders for drug delivery |
US20060257324A1 (en) * | 2000-05-22 | 2006-11-16 | Chiesi Farmaceutici S.P.A. | Pharmaceutical solution formulations for pressurised metered dose inhalers |
AU2000265583A1 (en) | 2000-08-15 | 2002-02-25 | Carsten Berg | Quaternary ammonium salts of 1,2-benzisothiazolin-3-one. preparation and use as biocides |
FI20002215A0 (fi) | 2000-10-06 | 2000-10-06 | Orion Yhtymae Oyj | Yhdistelmäpartikkelit |
US20040081627A1 (en) * | 2000-10-09 | 2004-04-29 | Jinks Phillip A | Medicinal aerosol formulations |
US6908928B2 (en) * | 2000-10-12 | 2005-06-21 | Bi Pharma Kg. | Crystalline tiotropium bromide monohydrate, processes for the preparation thereof, and pharmaceutical compositions |
WO2002043702A2 (en) * | 2000-11-30 | 2002-06-06 | Vectura Limited | Pharmaceutical compositions for inhalation |
ATE517607T1 (de) * | 2000-11-30 | 2011-08-15 | Vectura Ltd | Verfahren zur herstellung von partikeln zur verwendung in einer pharmazeutischen zusammensetzung |
GB0029562D0 (en) | 2000-12-04 | 2001-01-17 | Novartis Ag | Organic compounds |
EP1345629A2 (en) | 2000-12-29 | 2003-09-24 | Advanced Inhalation Research, Inc. | Particles for inhalation having sustained release properties |
US20020141946A1 (en) * | 2000-12-29 | 2002-10-03 | Advanced Inhalation Research, Inc. | Particles for inhalation having rapid release properties |
ITMI20010428A1 (it) * | 2001-03-02 | 2002-09-02 | Chemo Breath S A | Composizioni ad uso inalatorio a base di formoterolo |
WO2002080859A2 (en) * | 2001-03-20 | 2002-10-17 | Glaxo Group Limited | Inhalation drug combinations |
RU2294737C2 (ru) | 2001-03-30 | 2007-03-10 | Яготек Аг | Медицинские аэрозольные составы |
US20050074742A1 (en) * | 2001-03-30 | 2005-04-07 | Alain Domard | Cartilaginous neo-tissue capable of being grafted |
US6667344B2 (en) | 2001-04-17 | 2003-12-23 | Dey, L.P. | Bronchodilating compositions and methods |
US6848197B2 (en) | 2001-04-18 | 2005-02-01 | Advanced Inhalation Research, Inc. | Control of process humidity to produce large, porous particles |
DE10130371A1 (de) | 2001-06-23 | 2003-01-02 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Anticholinergika, Corticosteroiden und Betamimetika |
US20030018019A1 (en) * | 2001-06-23 | 2003-01-23 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics |
TWI324934B (en) * | 2001-08-28 | 2010-05-21 | Schering Corp | Pharmaceutical compositions for the treatment of asthma |
DE10202940A1 (de) | 2002-01-24 | 2003-07-31 | Sofotec Gmbh & Co Kg | Patrone für einen Pulverinhalator |
US7244415B2 (en) | 2002-03-28 | 2007-07-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | HFA suspension formulations of an anhydrate |
DE10214264A1 (de) * | 2002-03-28 | 2003-10-16 | Boehringer Ingelheim Pharma | HFA-Suspensionsformulierungen eines Anhydrats |
GB0207906D0 (en) * | 2002-04-05 | 2002-05-15 | 3M Innovative Properties Co | Formoterol and mometasone aerosol formulations |
DE10216429A1 (de) | 2002-04-12 | 2003-10-23 | Boehringer Ingelheim Pharma | Arzneimittel enthaltend Steroide und ein neues Anticholinergikum |
WO2004014293A2 (en) * | 2002-06-12 | 2004-02-19 | Epigenesis Pharmaceuticals, Inc. | Combination of anti-muscarinic agents and non-glucocorticoid steroids |
DE10237739A1 (de) | 2002-08-17 | 2004-02-26 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Inhalative Arzneimittel enthaltend ein neues Anticholinergikum in Kombination mit Corticosteroiden und Betamimetika |
US7244742B2 (en) * | 2002-08-17 | 2007-07-17 | Boehringer Ingelheim Pharma Gmbh & Co Kg | Pharmaceutical compositions for inhalation containing an anticholinergic, corticosteroid and betamimetic |
JP2005536538A (ja) | 2002-08-23 | 2005-12-02 | シェーリング コーポレイション | 薬学的組成物 |
CN1694689A (zh) | 2002-09-30 | 2005-11-09 | 阿库斯菲尔公司 | 供吸入的缓释多孔微粒 |
ES2331793T3 (es) * | 2002-10-15 | 2010-01-15 | Cryovac, Inc. | Procedimiento para estimular, almacenar y distribuir un captador de oxigeno, y un captador de oxigeno almacenado. |
EP1452179A1 (en) | 2003-02-27 | 2004-09-01 | CHIESI FARMACEUTICI S.p.A. | Novel medicament combination of a highly potent long-lasting beta2-agonist and a corticosteroid |
DE10323966A1 (de) | 2003-05-27 | 2004-12-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue langwirksame Arzneimittelkombinationen zur Behandlung von Atemwegserkrankungen |
KR20060015316A (ko) | 2003-05-28 | 2006-02-16 | 넥타르 테라퓨틱스 | 아미노산 및/또는 인지질로 부분 또는 완전 코팅된수불용성 활성제 미립자의 제조를 위한 알코올성 수용액의분무 건조법 |
CA2529007C (en) * | 2003-06-16 | 2012-03-27 | Altana Pharma Ag | Composition comprising a pulmonary surfactant and a pde5 inhibitor for the treatment of lung diseases |
SE527190C2 (sv) * | 2003-06-19 | 2006-01-17 | Microdrug Ag | Inhalatoranordning samt kombinerade doser av en beta2-agonist, ett antikolinergiskt medel och ett antiinflammatorisk steroid |
EP1651221B1 (en) | 2003-07-28 | 2009-01-14 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising betamimetics and an anticholinergic agent |
WO2005014005A1 (en) | 2003-07-29 | 2005-02-17 | Boehringer Ingelheim International Gmbh | Combination of an anticholinergic and a steroid and its use to treat respiratory disorders by inhalation |
EP1803469A3 (en) | 2003-07-29 | 2011-10-26 | Boehringer Ingelheim Pharma GmbH & Co. KG | Medicaments for inhalation comprising betamimetics and an anticholinergic |
JP2007500676A (ja) | 2003-07-31 | 2007-01-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 抗コリン作用薬とベータ受容体刺激薬を含む吸入用薬剤 |
EP1925293A3 (en) | 2003-10-20 | 2010-01-13 | Schering Corporation | Pharmaceutical aerosol compositions |
US9308199B2 (en) * | 2004-04-29 | 2016-04-12 | Honeywell International Inc. | Medicament formulations |
CA2543858C (en) * | 2003-11-21 | 2014-04-15 | Theravance, Inc. | Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
SE0303270L (sv) * | 2003-12-03 | 2005-06-04 | Microdrug Ag | Metod för administration av tiotropium |
KR20070007075A (ko) | 2003-12-31 | 2007-01-12 | 사이덱스 인크 | 술포알킬 에테르 시클로덱스트린 및 코르티코스테로이드를함유한 흡입용 제형 |
SI1718336T1 (sl) | 2004-02-06 | 2008-10-31 | Meda Pharma Gmbh & Co Kg | Nova kombinacija antiholinergika in beta mimetikov za zdravljenje respiratornih bolezni |
JP4819699B2 (ja) | 2004-02-06 | 2011-11-24 | メダ ファーマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディト ゲゼルシャフト | 喘息及びcopdの長期間の治療のための抗コリン作用薬及びグルココルチコイドの組合せ剤 |
US20050287077A1 (en) * | 2004-02-10 | 2005-12-29 | James E. Shipley | Process for preparing stable SOL of pharmaceutical ingredients and hydrofluorocarbon |
GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
KR20070026604A (ko) * | 2004-06-18 | 2007-03-08 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 기관지 감염의 치료 방법 |
GB0426301D0 (en) * | 2004-11-30 | 2004-12-29 | Vectura Ltd | Pharmaceutical formulations |
US20060140873A1 (en) | 2004-12-27 | 2006-06-29 | Chang Heng W | Aerosol pharmaceutical compositions |
EP1861361A1 (en) | 2005-03-24 | 2007-12-05 | Sosei R&D Ltd. | Glycopyrronium salts and their therapeutic use |
WO2006105401A2 (en) | 2005-03-30 | 2006-10-05 | Schering Corporation | Medicaments and methods combining an anticholinergic, a corticosteroid, and a long acting beta agonist |
WO2006114379A1 (de) | 2005-04-23 | 2006-11-02 | Boehringer Ingelheim International Gmbh | Arzneimittelkombination für die inhalation enthaltend neben einem anticholinergikum ein betamimetikum und ein steroid |
GB0523653D0 (en) | 2005-11-21 | 2005-12-28 | Novartis Ag | Organic compounds |
JP2008542332A (ja) | 2005-05-31 | 2008-11-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 呼吸器疾患治療用新規医薬組成物 |
EP1898894A1 (en) | 2005-06-17 | 2008-03-19 | Boehringer Ingelheim International GmbH | Mrp iv inhibitors for the treatment of respiratory diseases |
US8475845B2 (en) | 2005-07-15 | 2013-07-02 | Map Pharmaceuticals, Inc. | Method of particle formation |
AU2006269961B2 (en) | 2005-07-15 | 2012-07-19 | Map Pharmaceuticals, Inc. | Multiple active pharmaceutical ingredients combined in discrete inhalation particles and formulations thereof |
CN100560598C (zh) * | 2005-07-26 | 2009-11-18 | 上海奥锐特国际贸易有限公司 | 氟替卡松丙酸酯的合成方法 |
AT502396B1 (de) | 2005-09-01 | 2007-03-15 | Montanuniv Leoben | Verfahren zum abtrennen von verunreinigungen aus einsatzstoffen |
GB0523654D0 (en) | 2005-11-21 | 2005-12-28 | Novartis Ag | Organic compounds |
GB0523655D0 (en) | 2005-11-21 | 2005-12-28 | Novartis Ag | Organic compounds |
GB0523656D0 (en) | 2005-11-21 | 2005-12-28 | Novartis Ag | Organic compounds |
CA2632780C (en) | 2005-12-21 | 2013-11-12 | Meda Pharma Gmbh & Co. Kg | Combination of r,r-glycopyrrolate, rolipram, and budesonide for the treatment of inflammatory diseases |
US8263645B2 (en) * | 2006-02-03 | 2012-09-11 | Pari Pharma Gmbh | Disodium cromoglycate compositions and methods for administering same |
WO2007095041A2 (en) | 2006-02-09 | 2007-08-23 | Schering Corporation | Pharmaceutical formulations |
JP2009537585A (ja) | 2006-05-24 | 2009-10-29 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 呼吸器疾患の治療のための新規医薬組成物 |
GB0613161D0 (en) | 2006-06-30 | 2006-08-09 | Novartis Ag | Organic Compounds |
GB0614621D0 (en) * | 2006-07-24 | 2006-08-30 | 3M Innovative Properties Co | Metered dose dispensers |
EP1894568A1 (en) * | 2006-08-31 | 2008-03-05 | Novartis AG | Pharmaceutical compositions for the treatment of inflammatory or obstructive airway diseases |
JP2010519195A (ja) * | 2007-02-19 | 2010-06-03 | シプラ・リミテッド | 薬学的組成物 |
EP1964564A1 (en) * | 2007-04-19 | 2008-09-03 | LAB International SRL | Breakthrough Pain Management |
EP2036572A1 (en) * | 2007-09-04 | 2009-03-18 | Novo Nordisk A/S | Process for drying a protein, a protein particle and a pharmaceutical composition comprising the protein particle |
CN101317821B (zh) * | 2007-11-15 | 2012-01-04 | 陈晓东 | 适用于肺部给药的超细干粉颗粒及其制备方法 |
BRPI0821186A2 (pt) * | 2007-12-13 | 2015-06-16 | Novartis Ag | Compostos orgânicos |
GB0801876D0 (en) | 2008-02-01 | 2008-03-12 | Vectura Group Plc | Suspension formulations |
FR2940162B1 (fr) | 2008-12-22 | 2011-02-25 | Boehm & Cie Ets | Outil de frappe multi-usages a mecanisme absorbant l'energie transmise au moyen de prehension |
WO2010097188A1 (en) * | 2009-02-25 | 2010-09-02 | Chiesi Farmaceutici S.P.A. | Inhalation particles comprising a salt of carmoterol and a corticosteroid |
AU2010253776B2 (en) * | 2009-05-29 | 2015-01-22 | Pearl Therapeutics, Inc. | Compositions for pulmonary delivery of long-acting muscarinic antagonists and long-acting B2 adrenergic receptor agonists and associated methods and systems |
US8815258B2 (en) * | 2009-05-29 | 2014-08-26 | Pearl Therapeutics, Inc. | Compositions, methods and systems for respiratory delivery of two or more active agents |
TR201811349T4 (tr) | 2010-04-01 | 2018-09-21 | Chiesi Farm Spa | İnhalasyon i̇çi̇n kuru toz taşiyici parti̇külleri̇n hazirlanmasi i̇çi̇n proses. |
JP2014504260A (ja) | 2010-10-15 | 2014-02-20 | グラクソ グループ リミテッド | 集合ナノ粒子状薬物製剤、その製造及び使用 |
EP2749277A3 (en) | 2011-02-17 | 2014-08-27 | Cipla Limited | Combination of glycopyrronium and vilanterol |
JO3510B1 (ar) | 2011-03-04 | 2020-07-05 | Heptares Therapeutics Ltd | استخدام جلايكوبيرولات لعلاج عدم انتظام دقات القلب |
SG194896A1 (en) | 2011-05-17 | 2013-12-30 | Pearl Therapeutics Inc | Compositions, methods & systems for respiratory delivery of two or more active agents |
RU2015154720A (ru) | 2013-05-22 | 2017-06-27 | Перл Терапьютикс, Инк. | Композиции, способы и системы для респираторной доставки трех или более активных средств |
-
2010
- 2010-05-28 AU AU2010253776A patent/AU2010253776B2/en active Active
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- 2010-05-28 WO PCT/US2010/036659 patent/WO2010138868A2/en active Application Filing
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- 2010-05-28 KR KR1020177016074A patent/KR20170070274A/ko not_active Application Discontinuation
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