JP2016521680A - 経鼻投与 - Google Patents
経鼻投与 Download PDFInfo
- Publication number
- JP2016521680A JP2016521680A JP2016504771A JP2016504771A JP2016521680A JP 2016521680 A JP2016521680 A JP 2016521680A JP 2016504771 A JP2016504771 A JP 2016504771A JP 2016504771 A JP2016504771 A JP 2016504771A JP 2016521680 A JP2016521680 A JP 2016521680A
- Authority
- JP
- Japan
- Prior art keywords
- nasal
- patient
- optionally
- sumatriptan
- carbon dioxide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Abstract
Description
図2(a)および図2(b)が、粉末エアロゾルをもたらす(deliver,配送する)ように動作することができるブレスパワー(Breath Powered)(商標)粉末送出装置(powder delivery device,粉末配送装置)を示している。
この検討の目的は、スマトリプタンの投与後の頭痛の緩和の発現を研究することにあった。436名の被験者を、研究対象の母集団とした。研究における処置を、(i)上述の実施形態のブレスパワー(商標)投与システムでの16mgのスマトリプタン粉末の経鼻投与、および(ii)有効物質を含んでいないブレスパワー(商標)投与システムを使用しつつ100mgのスマトリプタンを経口投与する経口錠剤の投与とした。
この実施例は、米国内の1つのセンターにおいて行われた健康な被験者における無作為の非盲検の単回投与の交差の相対的バイオアベイラビリティ研究を含む。研究対象の母集団を、研究者によって健康であると判断され、医療歴、身体検査、血液化学、血液学(完全血球算定を含む)、尿検査、生体信号、および心電図(ECG)によって判断される臨床的に関連する異常を有していない18〜55歳の男性および女性の20名の被験者とした。対象の被験者について、ボディマスインデックス(BMI)は18〜32kg/m2であり、体重は50kg以上であった。参加に先立ち、被験者は、研究における薬剤の各回の投与の前の48時間および拘束の期間の最中についてアルコールの摂取を控え、カフェイン/メチルキサンチンの摂取を研究の前の7日間および研究の継続期間について1日につき300mg未満に抑え、投与の前の24時間および拘束の最中は摂取しないことに同意した。さらに被験者は、最後の薬物動態サンプルの採取後まで研究日−1前の72時間についてグレープフルーツ、ダイダイ、またはキニンを含む食品または飲料(例えば、トニックウォータ)を消費せず、研究の最中にケシの実を含む食品を消費しないことに同意した。被験者を、両方の鼻孔を通る気流ならびに軟口蓋を閉じる能力(例えば、風船を膨らませる能力)について検証したところ、この実施例のブレスパワー(商標)装置を正しく使用することが可能であった。
図10〜12が、ブレスパワー(商標)(OptiNose社)送出装置およびImitrex(登録商標)鼻腔スプレー(GSK社)を使用して得られた健康な被験者のスマトリプタンPKパラメータと比較したニトログリセリン(GTN)誘起の偏頭痛についてのスマトリプタンPKパラメータを示している。
この研究は、20mgのスマトリプタンを両側にもたらすブレスパワー(商標)装置および100mgのスマトリプタン錠剤による二重盲研究である。この研究は、対象の各患者が各々の処置によって頭痛を処置するクロスオーバ設計である。具体的には、患者は、5回までの頭痛を一方の処置によって処置し、次いでクロスオーバにより、5回までの頭痛を他方の処置によって処置した。各々の頭痛において、患者は装置の使用および錠剤の摂取を行い、そのうちの一方だけを有効にした。今までのところ非盲検である400を超える頭痛についてのデータから、中程度または重度の頭痛について30分の時点において得られた結果(薬剤の摂取の30分後における頭痛の緩和)は、54%である。
メシル酸ジヒドロエルゴタミン(DHE)、スマトリプタン、ゾルミトリプタン、ブトルファノール、シバミド、およびリドカインの経鼻投与処方物がいずれも、偏頭痛および/または群発性頭痛の処置について使用/研究されている。シバミドおよびリドカインは、神経伝播を中断させるために鼻用スポイトによって投与されており、臨床効果の或る程度の証拠が存在しているが、頭痛の処置について米国食品医薬品局の承認を未だ受けていない。さらに、SPGの神経刺激が、群発性頭痛の進行停止において有望な結果を示しており、鼻腔からアクセスできる神経への局所処置の可能性を強く支持している。
研究の目的は、中程度〜激しい偏頭痛の患者の処置におけるブレスパワースマトリプタン粉末の効能および安全性を偽薬と比較することにある。経口トリプタンを摂取する患者は、一般的に、不満の理由として遅い作用の発現、不充分な痛みの緩和、および副作用に言及し、吐き気または嘔吐も使用の障壁となり得る。「トリプタン作用」として知られる副作用は、最も頻繁には、より高い血漿中濃度を生じる処方物および投与量に関係する。小さな試験において、ブレスパワー装置によってもたらされた少ない投与量のスマトリプタン粉末が、付随の副作用を伴うことなく、注射においてすでに報告された率に近い頭痛緩和率を生じた。
別の実施例において、ブレスパワー(商標)送出装置(BPPSIT)を用いた公称20mgのスマトリプタン乾燥粉末の投与において、16mgが鼻内にもたらされることが明らかになった。これは、この装置におけるスマトリプタンへの総曝露が、錠剤、鼻腔スプレー、または注射よりも少ない総ミリグラム投与量であることを意味する。しかしながら、直接な比較の薬物動態研究が、16mgのBPPSIT粉末処置が20mgの従来からの液体スマトリプタン鼻腔スプレーよりも高いピーク濃度(Cmax ng/mL)を生むことを示している(20.8mg対16.4mg、投与量についての調節なし)。両方の経鼻投与の処方物は、スマトリプタン錠剤(100mg錠剤=70.2,6mg)または皮下注射(6mg=111.6mg)よりも大幅に低いピーク濃度(Cmax ng/mL)を生む。同様に、曲線(AUC0 ng*hr/mL)の下方の面積によって測定される総薬剤曝露も、経鼻の処方物においては、100mgの錠剤(308.8mg)または注射(128.2mg)と比べてはるかに少ない(BPPSIT=64.9mg、従来からのスマトリプタン液体鼻腔スプレー=61.1mg、投与量についての調節なし)。BPPSITによって投与されるスマトリプタン粉末は、試験したいかなるスマトリプタン製品とも生物学的に同等ではない。とくに、BPPSITの薬物動態が、従来からの液体鼻腔スプレーと比べてより高速かつより効率的な吸収のパターンを示し、投与される薬剤が20%少ないにもかかわらずAUC0−15分が液体スマトリプタン鼻腔スプレーについて1.2であるのに対してBPPSITでは2.1であり、AUC0−30分が従来からのスプレーについて3.6であるのに対してBPPSITでは5.8であり、すなわち早期の血漿曝露が60%増しよりもさらに上回ることに、注目すべきである。
別の研究において、ブレスパワー(商標)Bi−Directional(商標)投与の際の鼻のpH測定結果を分析した。いくつかの態様において、これらのデータを、生体内で「装置効果」を確認するための現実的かつ利用可能な方法と考えることができる。しかしながら、鼻内のNOおよび二酸化炭素レベルの測定は、鼻から空気を常時吸い出す必要があり、流れのパターンを変化させてしまうと考えられるため、典型的には実現不可能である。
口蓋閉鎖ブレスパワー(商標)装置を使用した低用量のスマトリプタン粉末によるフェーズ2試験は、注射においてすでに報告された水準に近付く頭痛の緩和を生み出したが、トリプタン効果を伴わなかった。さらなる試験を、中程度〜激しい急性偏頭痛の患者において偽薬と比較したときのこの投与の形態の効能および安全性を評価するために企てた。これらの研究は、スクリーニングに先立つ12ヵ月において1〜8回/月の偏頭痛を経験している患者において実行されたフェーズ3、他施設、無作為化、二重盲検、偽薬対照、単回投与、並行群研究を含んだ。各々の患者は、中程度または激しい強度の単一の偏頭痛を、合計の投与量が22mgとなるように11mgのスマトリプタン粉末を含んでいるブレスパワー装置または偽薬が装てんされた同等の装置のいずれかの2回の投与(各々の鼻孔に1回ずつ)で処置した。以下の効能の結果が測定された。
120分の時点(主要)および120分までの複数の時点における頭痛反応(軽微または皆無と評価される痛み)。
120分までの複数の時点における完全な痛みの解放(頭痛の苦痛からの自由)。
有意な緩和までの時間(頭痛の苦痛の反応の解釈の患者による報告)。
臨床の無力および偏頭痛関連の症状(光恐怖症、音声恐怖症、吐き気、および嘔吐)。
救急薬の使用。
反応の持続/痛みの解放の持続(120分の時点において頭痛について効果があり/痛みが完全に消え、投与後24および48hまで再発生または救急薬の使用がない)。
上記提示の実施例および検討において、二酸化炭素は、治療または薬物動態に関する効果の提供および/または向上をもたらし、さらには/あるいは鼻道内の領域のpHの調節をもたらすための機構を提供するものとして説明されている。二酸化炭素は、鼻道において反応し、pHを下げることができる。上述のように、もたらされる二酸化炭素の濃度は、約5〜約6%vol/volの範囲であってよい。他の態様において、治療量の二酸化炭素は、約1%vol/vol超の二酸化炭素および約10%vol/vol未満の二酸化炭素を含むことができる。
鼻ポリープを有する慢性鼻副鼻腔炎の109名の患者における3ヵ月の偽薬対照研究において、ブレスパワー(商標)液体薬剤送出装置によるフルチカゾン(400μg、1日2回)の投与が、耐用性良好であり、症状および全体としてのポリープスコアの両者の大きな軽減を生み出すと報告された
実施例10と同じ薬剤−装置の組み合わせ製品を使用し、小規模な偽薬対照研究(N=20)を、ポリープのない術後の治療抵抗性CRSの患者において実行したところ、客観的指標および自覚症状の両者について臨床的に有意な改善がもたらされた。
Claims (40)
- 患者を治療的に処置するための装置または方法であって、
第1のステップにおいて治療薬を投与することと、
第2のステップにおいて患者の鼻道の内部の位置に治療量の二酸化炭素またはpH調節物質の少なくとも一方を配送することと
を含んでおり、
前記第1のステップが、前記第2のステップの前、後、前後、および/または前記第2のステップと同時に実行される、装置または方法。 - 前記第1のステップは、前記第2のステップの前に実行される、請求項1に記載の装置または方法。
- 前記第1のステップは、前記第2のステップの後に実行される、請求項1に記載の装置または方法。
- 前記第2のステップは、前記第1のステップの前および後の両方において実行され、かつ/または前記第1のステップは、前記第2のステップと同時に実行される、請求項1に記載の装置または方法。
- 前記位置は、鼻道の上後領域を含む、請求項1に記載の装置または方法。
- 前記治療薬は、任意選択でコハク酸スマトリプタンの形態であり、任意選択で粉末エアロゾルとして投与されるスマトリプタンを含む、請求項1に記載の装置または方法。
- 前記治療薬は、任意選択でフルチカゾンであり、任意選択でプロピオン酸フルチカゾンの形態であり、任意選択で液体エアロゾルとして投与される、局所ステロイドを含む、請求項1に記載の装置または方法。
- 前記治療薬は、少なくとも100ugの量で、任意選択で1日に2回配送される、請求項7に記載の装置または方法。
- 前記治療薬は、少なくとも200ugの量で、任意選択で1日に2回配送される、請求項8に記載の装置または方法。
- 前記治療薬は、少なくとも400ugの量で、任意選択で1日に2回配送される、請求項9に記載の装置または方法。
- 前記配送する行為は、
マウスピースを患者の口に配置し、前記マウスピースに連通したノーズピースを患者の鼻孔に配置することと、
患者が前記マウスピースに息を吐き出し、前記ノーズピースから出る流体の流れを生成することと
を含んでおり、
経鼻投与されるときの前記治療薬は、前記配送する行為によらずに経鼻投与されるときの50ugの前記治療薬の全身バイオアベイラビリティと比べて同等またはそれ以下の全身バイオアベイラビリティまたは薬物動態(PK)プロフィルを有する、請求項8に記載の装置または方法。 - 前記第2のステップは、前記鼻道の位置におけるpHを、約0.01〜約0.5pH単位の範囲の量だけ調節する、請求項1に記載の装置または方法。
- 前記量は、約0.1〜約0.2pH単位の範囲である、請求項12に記載の装置または方法。
- 前記第2のステップは、二酸化炭素が約1%vol/vol〜約10%vol/volの二酸化炭素濃度を配送するステップを含む、請求項1に記載の装置または方法。
- 前記二酸化炭素濃度は、二酸化炭素が約5%〜約6%vol/volである、請求項14に記載の装置または方法。
- 前記配送する行為は、
マウスピースを患者の口に配置し、ノーズピースを患者の鼻孔に配置することと、
患者が前記マウスピースに息を吐き出し、前記ノーズピースから出る流体の流れを生成することと、
前記流体の流れを鼻道の内部の前記位置に導くことと
を含む、請求項1に記載の装置または方法。 - 前記配送する行為は、前記流体の流れを制御することによって前記位置におけるpHを調節することをさらに含む、請求項16に記載の方法。
- 前記流体の流れの制御は、前記流体の流れの継続時間、流量、圧力、および組成の少なくとも1つを制御することを含む、請求項17に記載の装置または方法。
- 前記流体の流れの継続時間を約2〜約3秒の範囲となるように制御することを含む、請求項18に記載の装置または方法。
- 前記流体の流れの流量を、少なくとも10L/分、任意選択で少なくとも20L/分、および任意選択で少なくとも30L/分に制御することを含む、請求項19に記載の装置または方法。
- 前記配送する行為は、
前記ノーズピースを患者の第2の鼻孔に配置することと、
患者が前記マウスピースに息を吐き出し、前記ノーズピースから出る第2の流体の流れを生成することと、
前記第2の流体の流れを第2の鼻道の内部の第2の位置に導くことと
を含む、請求項16に記載の装置または方法。 - 患者に配送される医薬品の治療効果を高めるための装置または方法であって、
鼻道の後方領域に約5%〜約6%vol/volの二酸化炭素を配送するように患者の鼻道に流体の流れを配送することと、
前記医薬品を患者に投与することと
を含む装置または方法。 - 鼻道の前記後方領域のpHを下げること
をさらに含む、請求項22に記載の装置または方法。 - 前記医薬品は、任意選択でコハク酸スマトリプタンの形態であり、任意選択で粉末エアロゾルとして投与される、スマトリプタンを含む、請求項22に記載の装置または方法。
- 前記医薬品は、任意選択でフルチカゾンであり、任意選択でプロピオン酸フルチカゾンの形態であり、任意選択で液体エアロゾルとして投与される、局所ステロイドを含む、請求項22に記載の装置または方法。
- 前記医薬品は、少なくとも100ugの量で、任意選択で1日に2回配送される、請求項25に記載の装置または方法。
- 前記医薬品は、少なくとも200ugの量で、任意選択で1日に2回配送される、請求項26に記載の装置または方法。
- 前記医薬品は、少なくとも400ugの量で、任意選択で1日に2回配送される、請求項27に記載の装置または方法。
- 前記配送する行為は、
マウスピースを患者の口に配置し、前記マウスピースに連通したノーズピースを患者の鼻孔に配置することと、
患者が前記マウスピースに息を吐き出し、前記ノーズピースから出る流体の流れを生成することと
を含んでおり、
経鼻投与されるときの前記医薬品は、前記配送する行為によらずに経鼻投与されるときの50ugの前記医薬品の全身バイオアベイラビリティまたは薬物動態(PK)プロフィルと比べて同等またはそれ以下の全身バイオアベイラビリティまたは薬物動態(PK)プロフィルを有する、請求項26に記載の装置または方法。 - 患者を処置するための装置または方法であって、
治療的または薬物動態的な効果をもたらすべく少なくとも約0.1pH単位だけ鼻道の上後領域のpHを下げるために患者の鼻孔に約5%〜約6%vol/volの濃度の二酸化炭素を配送すること
を含む装置または方法。 - 治療薬を患者に経口、経鼻、静脈内、および皮下の少なくとも1つにて投与すること
をさらに含む、請求項30に記載の装置または方法。 - 1回分のスマトリプタン粉末を経鼻投与すること
をさらに含む、請求項30に記載の装置または方法。 - 前記少量が、20mg未満のスマトリプタン粉末、任意選択で約16mgのスマトリプタン粉末を含み、任意選択でコハク酸スマトリプタンの形態である、請求項32に記載の装置または方法。
- 任意選択でフルチカゾンであり、任意選択でプロピオン酸フルチカゾンの形態であり、任意選択で液体エアロゾルとして投与される、局所ステロイドを投与すること
をさらに含む、請求項30に記載の装置または方法。 - 前記ステロイドは、少なくとも100ugの量で、任意選択で1日に2回配送される、請求項34に記載の装置または方法。
- 前記ステロイドは、少なくとも200ugの量で、任意選択で1日に2回配送される、請求項35に記載の装置または方法。
- 前記ステロイドは、少なくとも400ugの量で、任意選択で1日に2回配送される、請求項36に記載の装置または方法。
- 前記配送する行為は、
マウスピースを患者の口に配置し、前記マウスピースに連通したノーズピースを患者の鼻孔に配置することと、
患者が前記マウスピースに息を吐き出し、前記ノーズピースから出る流体の流れを生成することと
を含んでおり、
経鼻投与されるときの前記ステロイドは、前記配送する行為によらずに経鼻投与されるときの50ugの前記ステロイドの全身バイオアベイラビリティまたは薬物動態(PK)プロフィルと比べて同等またはそれ以下の全身バイオアベイラビリティまたは薬物動態(PK)プロフィルを有する、請求項30に記載の装置または方法。 - 前記治療的または薬物動態的な効果は、偏頭痛およびアレルギ性鼻炎の少なくとも一方を処置する、請求項30に記載の装置または方法。
- 前記配送する段階において患者の軟口蓋を実質的に閉じること
をさらに含む、請求項30に記載の装置または方法。
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EP (2) | EP2978482B1 (ja) |
JP (1) | JP6675974B2 (ja) |
KR (1) | KR102345816B1 (ja) |
CN (1) | CN105263551A (ja) |
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MX (1) | MX2015013774A (ja) |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020073510A (ja) * | 2014-03-26 | 2020-05-14 | オプティノーズ アズ | 経鼻投与 |
US11554229B2 (en) | 2013-03-26 | 2023-01-17 | OptiNose Inc. | Nasal administration |
Families Citing this family (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0215270D0 (en) | 2002-07-02 | 2002-08-14 | Optinose As | Nasal devices |
GB0311570D0 (en) | 2003-05-20 | 2003-06-25 | Optinose As | Delivery device and method |
GB0319119D0 (en) | 2003-08-14 | 2003-09-17 | Optinose As | Delivery devices |
GB0320171D0 (en) | 2003-08-28 | 2003-10-01 | Optinose As | Delivery devices |
GB0420513D0 (en) | 2004-09-15 | 2004-10-20 | Optinose As | Powder delivery devices |
GB0503738D0 (en) | 2005-02-23 | 2005-03-30 | Optinose As | Powder delivery devices |
US10478574B2 (en) | 2006-01-19 | 2019-11-19 | Optinose As | Nasal administration |
GB0604444D0 (en) | 2006-03-06 | 2006-04-12 | Optinose As | Nasal devices |
GB0605799D0 (en) | 2006-03-23 | 2006-05-03 | Optinose As | Nasal delivery devices |
GB2438834A (en) | 2006-06-08 | 2007-12-12 | Optinose As | Intranasal protein administration |
GB2440316A (en) | 2006-07-25 | 2008-01-30 | Optinose As | Nasal inhaler with scrubber |
GB0623728D0 (en) | 2006-11-28 | 2007-01-10 | Optinose As | Delivery devices |
GB0623731D0 (en) | 2006-11-28 | 2007-01-10 | Optinose As | Delivery device |
GB0623732D0 (en) | 2006-11-28 | 2007-01-10 | Optinose As | Powder delivery devices |
GB2448193A (en) | 2007-04-05 | 2008-10-08 | Optinose As | Nasal delivery device |
GB2448183A (en) | 2007-04-05 | 2008-10-08 | Optinose As | Nasal powder delivery device |
GB0719299D0 (en) | 2007-10-03 | 2007-11-14 | Optinose As | Nasal delivery devices |
GB201015371D0 (en) | 2010-09-14 | 2010-10-27 | Optinose As | Nasal delivery |
US9949923B2 (en) | 2011-03-15 | 2018-04-24 | Optinose As | Nasal delivery |
IN2014DN07610A (ja) | 2012-02-24 | 2015-05-15 | Optinose As | |
RU2640008C2 (ru) | 2012-02-24 | 2017-12-25 | Оптиноуз Ас | Назальное устройство подачи вещества |
US10076614B2 (en) | 2012-02-24 | 2018-09-18 | Optinose As | Nasal delivery devices |
USD761951S1 (en) | 2013-05-23 | 2016-07-19 | Optinose As | Nosepiece unit |
EP2868334B1 (de) | 2013-11-05 | 2017-01-11 | Benedict Gerber | Nasendusche |
MX2016017038A (es) * | 2014-06-25 | 2017-05-01 | Optinose As | Administracion nasal. |
US9925351B2 (en) * | 2014-07-01 | 2018-03-27 | Jennifer K. Keener | Aromatherapy device |
US10940279B2 (en) | 2014-07-01 | 2021-03-09 | Jennifer K. Keener | Aromatherapy device |
KR20170086599A (ko) | 2014-11-19 | 2017-07-26 | 옵티노즈 에이에스 | 비강 내 투여 |
US11305077B2 (en) | 2016-09-14 | 2022-04-19 | Healthy Humming, LLC | Therapeutic device for treatment of conditions relating to the sinuses, nasal cavities, ear, nose and throat |
WO2018053079A1 (en) | 2016-09-14 | 2018-03-22 | Bogan Consulting Services, P.A. | Therapeutic device for treatment of conditions relating to the sinuses, nasal cavities, ear, nose and throat |
US11432993B2 (en) | 2016-09-14 | 2022-09-06 | Healthy Humming, LLC | Therapeutic device for treatment of conditions relating to the sinuses, nasal cavities, ear, nose and throat |
US11213641B2 (en) | 2016-09-14 | 2022-01-04 | Healthy Humming, LLC | Therapeutic device for treatment of conditions relating to the sinuses, nasal cavities, ear, nose and throat |
EA033231B1 (ru) * | 2017-02-17 | 2019-09-30 | Государственное Учреждение "Республиканский Научно-Практический Центр Оториноларингологии" (Рнпц Оториноларингологии) | Способ лечения хронического полипозного риносинусита у пациентов с аспириновой триадой |
US10368502B2 (en) | 2017-09-25 | 2019-08-06 | Multiple Energy Technologies Llc | Bioceramic and carbon-based hydroponic systems, methods and devices |
EP3773834A4 (en) | 2018-04-12 | 2021-12-22 | Rocket Science Health Corp. | DEVICE, SYSTEM AND METHOD FOR INTRANASAL DRUG ADMINISTRATION |
CN108704840B (zh) * | 2018-06-22 | 2024-03-29 | 镇江宝塑高分子材料有限公司 | 一种用于tpu聚氨酯弹性体生产的振动筛专用筛板 |
CN112879615A (zh) * | 2019-02-01 | 2021-06-01 | 费希尔派克医疗保健公司 | 泄压装置和其部件 |
CN112043927A (zh) * | 2020-09-29 | 2020-12-08 | 重庆市第四人民医院 | 一种内科临床用呼吸装置 |
US12005185B2 (en) | 2021-12-17 | 2024-06-11 | Belhaven BioPharma Inc. | Medical counter measures including dry powder formulations and associated methods |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10508004A (ja) * | 1994-08-20 | 1998-08-04 | ダンバイオシスト ユーケー リミテッド | 限定されたz電位を有するキトサンまたはその誘導体を含む薬剤移送組成物 |
JP2004538027A (ja) * | 1999-07-12 | 2004-12-24 | キャプニア インコーポレイテッド | 頭痛、鼻炎及び他のありふれた病気を治す方法及び装置 |
JP2006523630A (ja) * | 2003-04-16 | 2006-10-19 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 鼻用医薬製剤およびその使用方法 |
WO2007093791A2 (en) * | 2006-02-14 | 2007-08-23 | Optinose As | Delivery device and method |
WO2008078730A1 (ja) * | 2006-12-26 | 2008-07-03 | Translational Research, Ltd. | 経鼻投与用製剤 |
WO2012094283A2 (en) * | 2011-01-04 | 2012-07-12 | Ista Pharmaceuticals, Inc. | Bepotastine compositions |
WO2013123417A1 (en) * | 2012-02-16 | 2013-08-22 | Capnia, Inc. | Gas dispenser with diffusing nosepiece |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4689223A (en) * | 1986-04-24 | 1987-08-25 | T & R Chemicals, Inc. | Method of treating the symptoms of the common cold |
US5669377A (en) * | 1996-07-05 | 1997-09-23 | Fenn; Arthur C. | Nasal band and method for improved breathing |
US6470882B1 (en) * | 1997-09-29 | 2002-10-29 | Michael T. Newhouse | Pernasal application of aerosol medication |
GB0114272D0 (en) * | 2001-06-12 | 2001-08-01 | Optinose As | Nasal delivery device |
ES2439274T3 (es) * | 1999-03-03 | 2014-01-22 | Optinose As | Dispositivo de administración nasal |
US20070039615A1 (en) * | 1999-11-08 | 2007-02-22 | Capnia, Incorporated | Methods and apparatus for treating rhinitis |
JP2004500168A (ja) * | 1999-11-08 | 2004-01-08 | キャプニア インコーポレイテッド | ガスと薬剤とを共投与して両者の相乗効果で頭痛やアンギナ及び他の症状を軽減するための方法及び装置 |
AU2001272086A1 (en) | 2000-02-28 | 2001-09-12 | Capnia Incorporated | Method and apparatus for transcutaneous infusion of carbon dioxide for local relief of pain and other ailments |
US6613308B2 (en) * | 2000-09-19 | 2003-09-02 | Advanced Inhalation Research, Inc. | Pulmonary delivery in treating disorders of the central nervous system |
SE524990C2 (sv) * | 2002-04-12 | 2004-11-09 | Microdrug Ag | Preparation av terapeutiskt torrt pulver samt förfarande för uppdelning och spridning i luft av medicinskt pulver |
GB0210397D0 (en) * | 2002-05-07 | 2002-06-12 | Ferring Bv | Pharmaceutical formulations |
US20040037809A1 (en) * | 2002-06-28 | 2004-02-26 | Nastech Pharmaceutical Company Inc. | Compositions and methods for enhanced mucosal delivery of interferon beta |
GB2400565B (en) * | 2003-04-17 | 2005-03-02 | Bespak Plc | Nasal drug delivery |
US8524735B2 (en) * | 2005-05-18 | 2013-09-03 | Mpex Pharmaceuticals, Inc. | Aerosolized fluoroquinolones and uses thereof |
US20070169779A1 (en) * | 2006-01-24 | 2007-07-26 | Freeman Gary A | Reperfusion protection in resuscitation |
GB0604319D0 (en) * | 2006-03-03 | 2006-04-12 | Optinose As | Nasal delivery |
GB2440316A (en) * | 2006-07-25 | 2008-01-30 | Optinose As | Nasal inhaler with scrubber |
GB2448183A (en) * | 2007-04-05 | 2008-10-08 | Optinose As | Nasal powder delivery device |
WO2008132224A2 (en) * | 2007-04-30 | 2008-11-06 | Novo Nordisk A/S | Method for drying a protein composition, a dried protein composition and a pharmaceutical composition comprising the dried protein |
EP2167040A1 (en) * | 2007-06-07 | 2010-03-31 | MDRNA, Inc. | Intranasal carbetocin formulations and methods for the treatment of autism |
DE102011103347B4 (de) * | 2011-05-27 | 2014-10-30 | Meda Pharma Gmbh & Co. Kg | Nasale pharmazeutische Formulierung |
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- 2016-08-03 HK HK16109258.0A patent/HK1221672A1/zh unknown
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Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10508004A (ja) * | 1994-08-20 | 1998-08-04 | ダンバイオシスト ユーケー リミテッド | 限定されたz電位を有するキトサンまたはその誘導体を含む薬剤移送組成物 |
JP2004538027A (ja) * | 1999-07-12 | 2004-12-24 | キャプニア インコーポレイテッド | 頭痛、鼻炎及び他のありふれた病気を治す方法及び装置 |
JP2006523630A (ja) * | 2003-04-16 | 2006-10-19 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 鼻用医薬製剤およびその使用方法 |
WO2007093791A2 (en) * | 2006-02-14 | 2007-08-23 | Optinose As | Delivery device and method |
WO2008078730A1 (ja) * | 2006-12-26 | 2008-07-03 | Translational Research, Ltd. | 経鼻投与用製剤 |
WO2012094283A2 (en) * | 2011-01-04 | 2012-07-12 | Ista Pharmaceuticals, Inc. | Bepotastine compositions |
WO2013123417A1 (en) * | 2012-02-16 | 2013-08-22 | Capnia, Inc. | Gas dispenser with diffusing nosepiece |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11554229B2 (en) | 2013-03-26 | 2023-01-17 | OptiNose Inc. | Nasal administration |
JP2020073510A (ja) * | 2014-03-26 | 2020-05-14 | オプティノーズ アズ | 経鼻投与 |
Also Published As
Publication number | Publication date |
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JP6675974B2 (ja) | 2020-04-08 |
AU2014242658A1 (en) | 2015-11-12 |
US20150053201A1 (en) | 2015-02-26 |
BR112015024869A2 (pt) | 2017-07-18 |
KR20150138286A (ko) | 2015-12-09 |
IL241875B (en) | 2022-03-01 |
MX2015013774A (es) | 2016-02-29 |
PL2978482T3 (pl) | 2022-10-03 |
WO2014155192A2 (en) | 2014-10-02 |
EP2978482B1 (en) | 2022-05-18 |
EP2978482A2 (en) | 2016-02-03 |
US20160045687A1 (en) | 2016-02-18 |
AU2019200191A1 (en) | 2019-01-31 |
SG11201507981TA (en) | 2015-10-29 |
RU2015145449A (ru) | 2017-05-03 |
KR102345816B1 (ko) | 2021-12-30 |
DK2978482T3 (da) | 2022-06-27 |
CA2908232A1 (en) | 2014-10-02 |
HK1221672A1 (zh) | 2017-06-09 |
CN105263551A (zh) | 2016-01-20 |
US20160367774A1 (en) | 2016-12-22 |
BR112015024869A8 (pt) | 2019-12-17 |
ES2920802T3 (es) | 2022-08-09 |
ZA201507918B (en) | 2017-04-26 |
EP4062939A1 (en) | 2022-09-28 |
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