JP6429788B6 - 化合物送達のためのデバイス - Google Patents
化合物送達のためのデバイス Download PDFInfo
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- JP6429788B6 JP6429788B6 JP2015544216A JP2015544216A JP6429788B6 JP 6429788 B6 JP6429788 B6 JP 6429788B6 JP 2015544216 A JP2015544216 A JP 2015544216A JP 2015544216 A JP2015544216 A JP 2015544216A JP 6429788 B6 JP6429788 B6 JP 6429788B6
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Description
[0001] 本出願は、2012年11月28日に出願された米国仮出願第61/730,738号、2013年3月15日に出願された第61/794,601号、2013年6月6日に出願された第61/831,992号、2013年10月4日に出願された第61/887,045号の利益を主張する。これらの出願は引用により全体が本願にも含まれるものとする。
をデバイスに実行させる。一部の例では、プログラマブルコントローラは1つ以上の電子デバイスに接続されている。一部の例では、接続はローカル又はリモートである。一部の例では、接続は有線接続を含む。一部の例では、接続は無線接続を含む。一部の例では、1つ以上の電子デバイスは、コンピュータ、スマートフォン、又は携帯電話を含む。一部の例では、デバイスは更に、インターネットにアクセスする能力を備える。
[0094] 本明細書において提供されるのは、被験者への薬剤の電子送達のためのデバイス、システム、キット、組成物、コンピュータ読み取り可能媒体、及び方法である。例えばこのデバイス、システム、コンピュータ読み取り可能媒体、及び方法は、気晴らしのためのニコチン送達、完全もしくは部分的な禁煙を容易にするか、又はニコチン摂取の完全もしくは部分的な停止を容易にすることができる電子ニコチン送達のために使用可能である。被験者はヒトとすることができる。ヒトの被験者は、喫煙者か、又はタバコもしくはニコチン含有製品を用いる個人とすればよい。本明細書に記載するデバイスは、薬剤(例えばニコチン)を含むエアロゾルを発生させることができ、この薬剤(例えばニコチン)エアロゾルは、既知の一貫した量の薬剤(例えばニコチン)を有することができる。また、用量滴定のためのデバイス及び方法も提供される。
[00102] 図1は、肺の深部への送達及び即効性の薬物動態のためにエアロゾル粒径を制御し縮小するための電子薬剤(例えばニコチン)送達デバイスの一実施形態を示す。例えばニコチン(102)のような薬剤が、薬剤(例えばニコチン)容器(104)内に収容されており、投与機構(106)内へ吸い上げることができる。薬剤(例えばニコチン)小滴は、吸入されると、投与機構の外に引き出される。小さい小滴は、気道(108)内の空気流内に入る。ヒータ(110)は、バッテリ(112)と電気的に通信状態とすることができる。大きい小滴は慣性によりヒータ(110)に当たって堆積し、気化して、小さくなる。空気流及び気化速度を制御することにより、蒸気は凝縮して最適なサイズのエアロゾルを形成する。
[00103] 本明細書において提供される電子薬剤(例えばニコチン)送達デバイスは、一貫した既知の量で薬剤(例えばニコチン)の用量を与えることができる。薬剤(例えばニコチン)の用量は、約1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、88、89、90、91、92、93、94、95、96、97、98、99、100、101、102、103、104、105、106、107、108、109、110、111、112、113、114、115、116、117、118、119、120、121、122、123、124、125、126、127、128、129、130、131、132、133、134、135、136、137、138、139、140、141、142、143、144、145、146、147、148、149、150、151、152、153、154、155、156、157、158、159、160、161、162、163、164、165、166、167、168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、193、194、195、196、197、198、199、200、201、202、203、204、205、206、207、208、209、210、211、212、213、214、215、216、217、218、219、220、221、222、223、224、225、226、227、228、229、230、231、232、233、234、235、236、237、238、239、240、241、242、243、244、245、246、247、248、249、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、510、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000μgであるか、これらのいずれかより多いか、これらのいずれかより少ないか、又は少なくともこれらのいずれかである薬剤(例えばニコチン)とすることができる。一部の例では、デバイスが送達することができる薬物の用量は、約1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、88、89、90、91、92、93、94、95、96、97、98、99、又は100mgであるか、これらのいずれかより多いか、これらのいずれかより少ないか、又は少なくともこれらのいずれかの用量である。
[00107] 本明細書において、薬剤(例えばニコチン)チャレンジ用量(challenge dose)を被験者に投与するための方法が提供される。一部の例では、被験者はヒトである。場合によっては、被験者は、タバコ又はニコチン含有製品を吸うか又は他の方法で用いるヒトである。本明細書において、被験者の肺の深部への送達に効果的な空気動力学的中央粒子径(MMAD)備えた粒子を含む凝縮エアロゾルを発生させるための方法が提供される。この方法は、薬学的に活性な薬剤(例えばニコチン)を含む液体調合物を通路に供給又は送出することと、通路内のヒータ要素を用いて液体調合物を気化させて気化液体調合物を生成することと、気化液体調合物を肺の深部への送達に効果的なサイズを有する粒子に凝縮可能とするのに効果的な流量で、通路を介してキャリアガスを流すことと、を備えることができる。凝縮後の粒径は、約1から約5μmのMMADとすることができる。流量は、例えば約1から約15水柱インチ(約249Paから約3738Paの範囲)の真空で、約1から約10リットル/分(LPM)(約1.667x10−5m3/sから約1.667x10−4m3/sの範囲)とすることができる。デバイスの流れ抵抗は、約0.05から約0.15(cmH2O)1/2/LPMとすることができる。液体調合物は、容器から供給又は送出すればよい。容器は例えば毛細管のようなチューブから成るものとすることができる。容器はヒータ要素と流体連通することができる。一部の例では、薬学的に活性な薬剤(例えばニコチン)を含む液体調合物は、容積移送式ポンプを用いてヒータ要素に送出される。容積移送式ポンプは、往復ポンプ、定量ポンプ、回転ポンプ、油圧ポンプ、蠕動ポンプ、歯車ポンプ、スクリューポンプ、可撓性インペラーポンプ、隔膜ポンプ、ピストンポンプ、又はプログレッシブキャビティポンプ、又は当技術分野において既知の容積移送を利用した他のいずれかのポンプとすればよい。容積移送式ポンプは、ヒータ要素と流体連通することができる。容積移送式ポンプは、薬学的に活性な薬剤(例えばニコチン)を収容する容器と流体連通するか又は流体結合することができる。容積移送式ポンプは、ヒータ要素又は薬学的に活性な薬剤(例えばニコチン)を収容する容器と流体連通することができる。薬学的に活性な薬剤(例えばニコチン)は液体調合物とすればよい。容積移送式ポンプは、通路内又は通路外にある場合がある。ヒータ要素は、本明細書において提供されるようないずれかのヒータ要素とすればよい。キャリアガスは空気とすることができる。
[00124] 一部の例では、薬剤(例えばニコチン)を1つ以上の他の物質と混合する。本明細書において提供するような薬剤(例えばニコチン)と混合した場合、混合物は室温において液体であり得る。本明細書において提供するような薬剤(例えばニコチン)と混合した場合、混合物はデバイスの使用中に液体であり、この液体混合物をデバイスの使用中にヒータ要素に送出することを可能とする。1つ以上の他の物質は、薬学的に許容可能な添加物又はキャリアとすることができる。適切である薬学的に許容可能な添加物又はキャリアは、揮発性又は不揮発性であり得る。揮発性の添加物は、加熱されると揮発し、エアロゾル化し、薬剤(例えばニコチン)と共に吸入することができる。そのような添加物のクラスは当技術分野において既知であり、限定ではないが、気体、超臨界流体、液体、及び固体の溶剤を含む。添加物/キャリアは、水;メタノール等のテルペン;エタノール、プロピレングリコール、グリセロール、及び他の同様のアルコール等のアルコール;ジメチルホルムアミド;ジメチルアセトアミド、ワックス;超臨界二酸化炭素;ドライアイス;及びそれらの混合物又は組み合わせとすればよい。
[00134] 本明細書に記載する電子薬剤(例えばニコチン)送達デバイスは、薬剤(例えばニコチン)混合物又はエアロゾルのpHを制御することができる。薬剤(例えばニコチン)混合物又はエアロゾルのpHは、約1、1.5、2、2.5、3、3.5、4、4.5、5、5.5、5.6、5.7、5.8、5.9、6、6.1、6.2、6.3、6.4、6.5、6.6、6.7、6.8、6.9、7、7.1、7.2、7.3、7.4、7.5、7.6、7.7、7.8、7.9、8、8.1、8.2、8.3、8.4、8.5、8.6、8.7、8.8、8.9、9、9.5、10、10.5、11、11.5、12、12.5、13、13.5、又は14であるか、これらのいずれかより高いか、これらのいずれかより低いか、又は少なくともこれらのいずれかの値であり得る。一部の例では、薬剤(例えばニコチン)混合物又はエアロゾルのpHは、約1から約14、約2から約13、約3から約12、約4から約11、約5から約10、約6から約9、約6から約8、約6から約7、約4から約6、約4から約8、約5から約8、約5から約7、約7から約9、約5.5から約8.5、約6.5から約8.5、約6.5から約7.5、約7.5から約9、又は約7から約8.5とすることができる。混合物のpHを調整するために、1つ以上の緩衝剤を混合物に追加することも可能である。
[00136] 一実施形態において、混合物は1つ以上の香料を含む。1つ以上の香料は、例えばFlavourart(イタリア国)が提供するフレーバー、Flavor Apprentice、又はLorAnnとすることができる。フレーバーは、例えばアーモンド、アーモンドアマレット、リンゴ、ババロア、ブラックチェリー、黒ゴマ、ブルーベリー、赤砂糖、風船ガム、バタースコッチ、カプチーノ、キャラメル、キャラメルカプチーノ、チーズケーキ(グラハムクラスト)、シナモンレッドホット、綿菓子、サーカス綿菓子、クローブ、ココナッツ、コーヒー、クリアコーヒー、ダブルチョコレート、エナジードリンク(energy cow)、グラハムクラッカー、グレープジュース、グリーンアップル、ハワイアンパンチ、ハチミツ、ジャマイカラム、ケンタッキーバーボン、キウイ、Koolada、レモン、レモンライム、タバコ、メープルシロップ、マラスキノチェリー、マシュマロ、メントール、ミルクチョコレート、モカ、マウンテンデュー、ピーナッツバター、ペカン、ペパーミント、ラズベリー、バナナ、完熟バナナ、ルートビール、RY4、スペアミント、イチゴ、スイートクリーム、スイートタルト、人工甘味料、焼きアーモンド、タバコ、タバコブレンド、バニラビーンアイスクリーム、バニラカップケーキ、バニラスアール、バニリン、ワッフル、ベルギーワッフル、スイカ、ホイップクリーム、ホワイトチョコレート、ウィンターグリーン、アマレット、バナナクリーム、クログルミ、ブラックベリー、バター、バターラム、サクランボ、チョコレートヘーゼルナッツ、シナモンロール、コーラ、クレームドマント、エッグノッグ、イングリッシュトフィー、グアバ、レモネード、リコリス、メープル、ミントチョコレートチップ、オレンジクリーム、ピーチ、ピニャコラーダ、パイナップル、プラム、ザクロ、プラリーヌクリーム、レッドリコリス、ソルトウォータートフィー、いちごバナナ、いちごキウイ、トロピカルパンチ、トゥッティフルッティ、又はバニラとすることができる。混合物中のフレーバーの数は、約1、2、3、4、5、6、7、8、9、10であるか、これらのいずれかより多いか、これらのいずれかより少ないか、又は少なくともこれらのいずれかとすることができる。
[00138] 本明細書において提供されるデバイスは、肺の深部に送達するのに最適な粒子径であり得るエアロゾルを発生させることができる。エアロゾルは凝縮エアロゾルとすればよい。粒径は、約0.01、0.015、0.02、0.025、0.03、0.035、0.04、0.045、0.05、0.055、0.06、0.065、0.07、0.075、0.08、0.085、0.09、0.095、0.1、0.11、0.12、0.13、0.14、0.15、0.16、0.17、0.18、0.19、0.2、0.21、0.22、0.23、0.24、0.25、0.26、0.27、0.28、0.29、0.3、0.31、0.32、0.33、0.34、0.35、0.36、0.37、0.38、0.39、0.4、0.41、0.42、0.43、0.44、0.45、0.46、0.47、0.48、0.49、0.5、0.51、0.52、0.53、0.54、0.55、0.56、0.57、0.58、0.59、0.6、0.61、0.62、0.63、0.64、0.65、0.66、0.67、0.68、0.69、0.7、0.71、0.72、0.73、0.74、0.75、0.76、0.77、0.78、0.79、0.8、0.81、0.82、0.83、0.84、0.85、0.86、0.87、0.88、0.89、0.9、0.91、0.92、0.93、0.94、0.95、0.96、0.97、0.98、0.99、1、1.5、2、2.5、3、3.5、4、4.5、5、5.5、6、6.5、7、7.5、8、8.5、9、9.5、10、10.5、11、11.5、12、12.5、13、13.5、14、14.5、15、15.5、16、16.5、17、17.5、18、18.5、19、又は20ミクロンであるか、これらのいずれかより大きいか、これらのいずれかより小さいか、又は少なくともこれらのいずれかの値であり得る。粒径は、約1から約10ミクロン、約1から約9ミクロン、約1から約7ミクロン、約1から約6ミクロン、約1から約5ミクロン、約1から約4ミクロン、約1から約3ミクロン、又は約1から約2ミクロンとすることができる。粒径は、約0.5から約10ミクロン、約0.5から約9.5ミクロン、約0.5から約9ミクロン、約0.5から約8.5ミクロン、約0.5から約8ミクロン、約0.5から約7.5ミクロン、約0.5から約7ミクロン、約0.5から約6.5ミクロン、約0.5から約6ミクロン、約0.5から約5.5ミクロン、約0.5から約5ミクロン、約0.5から約4.5ミクロン、約0.5から約4.0ミクロン、約0.5から約3.5ミクロン、約0.5から約3ミクロン、約0.5から約2.5ミクロン、約0.5から約2ミクロン、約0.5から約1.5ミクロン、又は約0.5から約1ミクロンとすることができる。粒径は1ミクロン未満とすることができる。粒径は5ミクロン超とすることができる。粒径は5ミクロン未満とすることができる。粒径は1ミクロン超とすることができる。一実施形態において、粒径は約1から約5ミクロンとすることができる。一実施形態では、粒径は約1から約3ミクロンとすることができる。一実施形態では、粒径は空気動力学的中央粒子径(MMAD)である。
[00140] 図4は、本明細書において提供される電子薬剤(例えばニコチン)送達デバイスにおいて使用可能な薬剤(例えばニコチン)容器(404)の実施形態を示す。バルブ(402)を有する例えば毛細管のようなチューブ(400)は、別個の容器内に挿入する必要はなく、排出端部から拡張することによって容器(404)自体とすることができる。例えば毛細管のようなチューブの直径を大きくして、もっと多くの混合物を収容することも可能である。混合物が出ていく際に抵抗となり得る低圧を生成することなく混合物を容器から引き出すことを可能とするため、後端は通気口(406)を有することができる。後端から薬剤(例えばニコチン)が気化又は蒸発することを阻止するため、容器の一部をワックス又はグリースプラグ等の柔らかい材料で充填することも可能である。このプラグ(408)は、混合物が用いられるにつれて容器に沿って引き出され得る。一実施形態では、薬剤(例えばニコチン)容器は円筒形である。一実施形態では、薬剤(例えばニコチン)容器は、1000mgのプロピレングリコールと混合された200mgの薬剤(例えばニコチン)を含む調合物を収容している。一実施形態では、薬剤(例えばニコチン)容器は、1000μgのプロピレングリコールと混合された200μgの薬剤(例えばニコチン)を含む調合物を収容している。一部の例では、薬剤(例えばニコチン)は液体調合物である。
[00147] 図2A及び図2Bは、電子ニコチン送達デバイスのコンポーネントの実施形態を示す。図2Aは、薬剤(例えばニコチン)容器(202)と、例えば毛細管のようなチューブ(204)と、を示す。図2Bは、このデバイスの拡大図を示す。薬剤(例えばニコチン)容器は、薬剤(例えばニコチン)/プロピレングリコール(PG)混合物(206)を含むことができる。例えば毛細管のようなチューブは、薬剤(例えばニコチン)/PGに親和性のある材料(208)で覆われて容器からの吸い上げを促進する内部領域を備えることができる。開口端部には、薬剤(例えばニコチン)/PGに親和性のない材料(210)(ポリテトラフルオロエチレン(PTFE)等)で覆われた内部領域を配置することができる。このコーティングによって、薬剤(例えばニコチン)/PGは開口端部に達する前に吸い上げを止めるので、空気に露出される混合物の表面積を小さくすることができ、空気中に薬剤(例えばニコチン)の蒸気は存在しない。例えば毛細管のようなチューブは、このチューブの加熱される部分(212)を備えることができ、これは加熱されるとチューブ内の混合物を気化及び膨張させ、開口端部から混合物を押し出すことができる。例えば毛細管のようなチューブ内の2つのくぼみ間にボール弁(214)を閉じ込めることができる。端部のくぼみは、ボールが流体によって押された場合にシールを形成するようになっている。この構成により、液体は加熱された場合に容器内に戻らずに端部から出ることができる。これら4つの要素は全て、例えば毛細管のようなチューブの端部から既知の用量の混合物を排出させ得るポンプを形成することができる。
[00149] バルブは逆止め弁とすることができる。逆止め弁は、ステンレス鋼等の金属で作成され得るか、又はナイロン、デルリン、又はホモポリマーアセタール等のプラスチックで作成され得るボールとすればよい。ボールは、例えば毛細管のようなチューブの内径より小さい直径を有して、薬剤(例えばニコチン)/PG混合物の吸い上げを可能とする。
[00150] ヒータ要素は、本明細書において提供されるようないずれかのヒータ要素とすればよい。ヒータ要素を用いて、本明細書において提供されるような薬学的に活性な薬剤を含む液体調合物から凝縮エアロゾルを発生させることができる。凝縮エアロゾルは、本明細書において提供されるような被験者の肺に送達するのに適した粒径を備えることができる。一部の例では、ヒータ要素はコイルを備えている。コイルはワイヤコイルとすればよい。コイルは更に、加熱することができる吸い上げ要素を備える。液体調合物がヒータ要素に送出されると、ヒータ要素はこれを気化させることができる。一部の例では、薬学的に活性な薬剤(例えばニコチン)を含む液体調合物は、容積移送式ポンプを用いてヒータ要素に送出される。容積移送式ポンプは、往復ポンプ、定量ポンプ、回転ポンプ、油圧ポンプ、蠕動ポンプ、歯車ポンプ、スクリューポンプ、可撓性インペラーポンプ、隔膜ポンプ、ピストンポンプ、又はプログレッシブキャビティポンプ、又は当技術分野において既知の容積移送を利用した他のいずれかのポンプとすればよい。容積移送式ポンプは、ヒータ要素と流体連通することができる。容積移送式ポンプは、薬学的に活性な薬剤(例えばニコチン)を収容する容器と流体連通するか又は流体結合することができる。容積移送式ポンプは、ヒータ要素又は薬学的に活性な薬剤(例えばニコチン)を収容する容器と流体連通することができる。薬学的に活性な薬剤(例えばニコチン)は液体調合物とすればよい。容積移送式ポンプは、通路内又は通路外に配置することができる。ヒータ要素は、電気抵抗性の材料を含むロッドを備えることができる。ロッドはワイヤとすればよい。ロッドは柔軟なロッドとすることができる。ロッドはコイルを備えることができ、ロッドのセグメントはコイルの内部を通過することができる。コイルはワイヤコイルとすればよい。ヒータ要素は、加熱することができる吸い上げ要素を備えることができる。加熱することができる吸い上げ要素は、コイルの中心を通ってそこから延出することができる。一部の例では、ヒータ要素は加熱可能な吸い上げ要素を備えている。ロッドは、加熱可能な吸い上げ要素を備えることができる。一部の例では、ロッドはコイル及び加熱可能な吸い上げ要素を備え、加熱可能な吸い上げ要素は、コイルの内部又は中心を通るロッドのセグメントである。
[00184] 一部の例では、毛細管内の気化に伴う問題が生じるおそれがある。第1に、材料を押し出す蒸気によって、液体の小滴が排出されることがある。第2に、高い蒸気濃度は毛細管端部内で高いことがあるので、最適な粒径よりも大きい粒径を生じ得る急速な凝縮及び凝結が起こる場合がある。エアロゾルの粒径を小さくするため、大きい粒子は除去して再気化させることができる。除去は、慣性衝突によって達成することができる(図11)。図11は、薬剤(例えばニコチン)容器(1104)、例えば毛細管のようなチューブ(1106)、ヒータ要素1(1108)、及びヒータ要素2(1110)を示す。考慮すべき1つの点は、ノズル(1102)のくびれによって空気流抵抗が許容できないほど大きくなり得るか否かということである。以下の式を用いて、オリフィス(DJ)(1112)の直径を計算することができる。
流量調節
[00223] 一部の例では、電子薬剤(例えばニコチン)送達デバイスは、電子タバコの寸法を備えている。電子薬剤(例えばニコチン)送達デバイスは、全体として円筒形の形状を有することができる。電子薬剤(例えばニコチン)送達デバイスは、可燃タバコに似せることができる。本明細書において提供されるような電子薬剤(例えばニコチン)送達デバイスの外径は、約0.001、0.0015、0.002、0.0025、0.003、0.0035、0.004、0.0045、0.005、0.0055、0.006、0.0065、0.007、0.0075、0.008、0.0085、0.009、0.0095、0.01、0.015、0.02、0.025、0.03、0.035、0.04、0.045、0.05、0.055、0.06、0.065、0.07、0.075、0.08、0.085、0.09、0.095、0.1、0.11、0.12、0.13、0.14、0.15、0.16、0.17、0.18、0.19、0.2、0.21、0.22、0.23、0.24、0.25、0.26、0.27、0.28、0.29、0.3、0.31、0.32、0.33、0.34、0.35、0.36、0.37、0.38、0.39、0.4、0.41、0.42、0.43、0.44、0.45、0.46、0.47、0.48、0.49、0.5、0.51、0.52、0.53、0.54、0.55、0.56、0.57、0.58、0.59、0.6、0.61、0.62、0.63、0.64、0.65、0.66、0.67、0.68、0.69、0.7、0.71、0.72、0.73、0.74、0.75、0.76、0.77、0.78、0.79、0.8、0.81、0.82、0.83、0.84、0.85、0.86、0.87、0.88、0.89、0.9、0.91、0.92、0.93、0.94、0.95、0.96、0.97、0.98、0.99、1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、又は30cmであるか、これらのいずれかより大きいか、これらのいずれかより小さいか、又は少なくともこれらのいずれかの値であり得る。本明細書において提供されるような電子薬剤(例えばニコチン)送達デバイスの外径は、約0.5cmから約1cm、約0.25cmから約0.75cm、約0.25cmから約1cm、又は約0.25cmから約1.5cmとすることができる。
[00226] 本明細書に記載する方法及びデバイスにおいて、いずれかの適切な薬剤(例えば薬物)を用いることができる。使用可能な薬剤(例えば薬学的に活性な薬剤)は、例えば以下のクラスの1つの薬剤を含む。麻酔、抗生物質、抗痙攣薬、抗鬱剤、抗糖尿病薬、解毒剤、抗嘔吐薬、抗ヒスタミン薬、抗感染薬、抗新生物薬、抗パーキンソン病薬、抗リウマチ薬、抗精神病薬、抗不安薬、食欲促進剤及び食欲抑制剤、血液調節剤、心血管作動薬、中枢神経刺激薬、アルツハイマー病管理薬、風邪薬、COPD(慢性閉塞性肺疾患)薬、咳止め薬、嚢胞性線維症の薬、診断薬、栄養補助食品、勃起障害の薬、胃腸薬、ホルモン、アルコール依存症の治療薬、依存症(addiction)の治療薬、免疫抑制薬、肥満細胞安定剤、偏頭痛用の製剤、乗り物酔い用の製品、多発性硬化症管理薬、筋弛緩薬、心筋梗塞の治療薬、非ステロイド性抗炎症薬、オピオイド、その他の鎮痛剤及び興奮剤、眼科用の製剤、骨粗鬆症の製剤、痛み止め、パニック治療薬、プロスタグランジン、呼吸器官の薬、鎮静薬及び催眠薬、皮膚及び粘膜の薬、禁煙補助薬、トゥーレット症候群の薬、尿路の薬、不眠症薬、減量薬、及びめ目まいの薬。一部の例では、薬剤はハーブ、サプリメント、又はビタミン剤である。
[00291] 本明細書に記載する方法及びデバイスにおいて用いられる、本明細書において提供されるようないずれの薬剤も、本明細書において提供されるような1つ以上の追加の物質を含む調合物内に存在し得る。一部の例では、1つの薬剤(例えばニコチン)及び1つ以上の追加の物質を含む調合物は液体調合物である。一部の例では、調合物は室温で液体である。一部の例では、液体調合物は、本明細書において提供されようなデバイスにおいて、本明細書において提供されるような容器に収容され、デバイスの動作温度において液体である。本明細書に記載されるようなデバイスのいずれの動作温度も、室温であるか、室温より低いか、又は室温より高いことがある。一部の例では、本明細書において提供されるような薬学的に活性な薬剤(例えばニコチン)を含む液体調合物は、本明細書において提供されるようなデバイスにおいて、ユーザがデバイスの出口又はマウスピースから吸入した場合に、本明細書において提供されるようなヒータ要素に液体として送出される。一部の例では、液体調合物は粘度の高い液体ではない。一部の例では、液体調合物はゲル状でもゲルでもない。一部の例では、本明細書において提供されるような薬学的に活性な薬剤(例えばニコチン)を含む液体調合物は、本明細書において提供されるようなヒータ要素上にいずれかの厚さの固体又はフィルムとして被覆されない。一部の例では、本明細書において記載されるような方法及びデバイスで用いられるニコチンを含む液体調合物は、増粘剤と混合されず、そのため粘度が低下している。すなわち、増粘剤と混合されたニコチンを含む液体調合物よりも粘度が低い。一部の例では、本明細書において提供されるようなデバイスをユーザ又は被験者が使用する前に、本明細書において提供されるような方法及びデバイスで用いられる液体調合物は、本明細書において提供されるようなヒータ要素上に塗布も被覆も行われない。一部の例では、薬学的に活性な薬剤を含む液体調合物は、デバイスの使用時にのみ、本明細書において提供されるようなデバイスにおけるヒータ要素に液体として送出される。デバイスの使用は、本明細書において与えられるようなユーザが、本明細書において提供されるようなデバイスの出口又はマウスピースで吸入又は引き込みを行うこととすればよい。一部の例では、出口又はマウスピースでの吸入によって、本明細書において提供されるようなデバイスの入口を介してデバイス内にキャリアガス(例えば空気)が引き込まれ、この入口を介したキャリアガス(例えば空気)の流れが、本明細書において提供されるような手段のいずれかによって薬学的に活性な薬剤(例えばニコチン)を含む液体調合物をデバイス内に含まれるヒータ要素に送出することを誘発する。デバイスは、本明細書において提供されるような1つ以上の入口を含むことができ、出口で吸入すると、1つ以上の入口から同時にキャリアガス(例えば空気)が引き込まれる。
概要
[00293] 本明細書において提供されるのは、モバイルデバイス、ウェブベースのデバイス、コンピュータ読み取り可能媒体、及びe−ヘルス対応の電子薬剤(例えばニコチン)送達プラットフォームを含むことができるe−ヘルスツールである。一部の例では、e−ヘルス対応の電子ニコチン送達プラットフォームは、デバイスのそれぞれのユーザに対して所定の時刻に所定のニコチン粒径で所定のニコチン用量を送達することによって、喫煙者がクリーンなニコチン送達に移行することを助けることができる。e−ヘルス対応の電子ニコチン送達プラットフォームは、特定のスケジュールでそれぞれのユーザにニコチンを提供することができ、これは、1日当たりの投与数、1日内の投与タイミング、又は1回の投与当たりのニコチン量を経時的に変化させることを伴う場合がある。一実施形態において、e−ヘルス対応の電子ニコチン送達プラットフォームは、完全な禁煙を達成するために用いられる。別の実施形態では、e−ヘルス対応の電子ニコチン送達プラットフォームは、喫煙の再発なく完全なニコチン停止又は禁煙を達成するために用いられる。別の実施形態では、e−ヘルス対応の電子ニコチン送達プラットフォームは、ニコチンの離脱症状なしで完全なニコチンからの離脱を達成するために用いられる。別の実施形態では、e−ヘルス対応の電子ニコチン送達プラットフォームを、他のニコチン置換療法、ニコチン作動薬、又は部分的作動薬(例えばバレニクリン又は他のいずれかのニコチン性アセチルコリン受容体のα4β2サブタイプ)と組み合わせて用いて、特定の喫煙目標(例えば完全な停止)の達成を助ける。別の実施形態では、e−ヘルスツールは、電子ニコチン送達デバイスからニコチン用量を投与する場合にユーザの安全性の確保を支援して、過量接種を防ぐことができる。
[00305] 目標をカスタム化することによって、完全な禁煙から、部分的な禁煙(例えば労働時間中は喫煙しない)、部分的又は完全なニコチン停止(例えばニコチン摂取を完全に止める)、認知力の改善まで、異なる喫煙者に対する多くの有利な健康上の利点を、同一のニコチン送達プラットフォームを用いて達成することが可能となる。一実施形態において、カスタム化された目標は、同一のニコチン送達プラットフォームを用いて完全な禁煙を達成することを可能とする。別の実施形態では、カスタム化された目標は、同一のニコチン送達プラットフォームを用いて完全なニコチン停止又は禁煙を再発なしで達成することを可能とする。別の実施形態では、カスタム化された目標は、同一のニコチン送達プラットフォームを用いて、ニコチン離脱症状なしで完全なニコチン離脱を達成することを可能とする。
[00308] 禁煙の際に喫煙再発が高率であること(多くの場合、90%を超える)は、ニコチンガム又はパッチのようなNRTを用いる場合であっても禁煙の試みの失敗が極めて多様なものであることを反映している。禁煙の試みの開始時にユーザ特性を体系的に追跡すること、投与パターンについて経時的に電子ニコチン送達デバイスの実際の使用を追跡すること、及び喫煙再発に関連した実世界のリスク要素を追跡することによって、電子ニコチン送達デバイスの使用を継続して喫煙再発のリスクを最小限に抑えるのに最適な使用パターン、用量、pH、粒径、及びその他の特性(例えば香料)を提案するために使用可能なアルゴリズムを生成することができる。これらのアルゴリズムは、ユーザの経験が増えることで常に向上させることができ、これによってアルゴリズムの経験的な基礎を強化し、いっそうロバストできめ細かいアルゴリズムを、それぞれのユーザのニコチン依存度及び健康上の目標に合うようにカスタム化することができる。
[00311] 可燃タバコ製品から移行する場合のユーザの目標は、経時的に変化することがある(例えば、最初は仕事の時だけ禁煙したいと思っていたユーザが、時間が経つにつれて完全な禁煙を選択するようになる可能性がある)。初期の使用及び用量アルゴリズムに対してユーザを注意深くマッチングし、その後で経時的に進行を監視することによって、それぞれの目標において最大の成功の可能性を保証するように調整を行うことができる。
[00314] 異なる用量特性(例えば用量、粒径、pH、気相対粒子相でのニコチン量、ニコチン送達装置から放出する空気速度、香料等)を体系的に変化させることで、ニコチンから分化強化の(differentially reinforcing)主観的報酬を生成することができる。ニコチンの用量特性を変化させることで、一定の目標(例えば禁煙)が達成される可能性を最大化することができる。
[00316] ニコチン用量の日常投与においては、ユーザは自身のニコチン依存度のレベルを査定することができず、一定の目標(例えば完全又は部分的なニコチン停止)の達成に挑戦することもできない。電子ニコチン送達デバイスを用いてユーザにニコチンのチャレンジ用量を投与することで、使用アルゴリズムの変更の容易さを査定し、ニコチン依存度の物理的及び心理的な側面を査定し、又は、例えばニコチン投与を完全に断つことが徐々に可能となってきていることをユーザに実証することができる。
[00318] 本明細書に記載する電子ニコチン送達デバイスを用いてニコチン投与を体系的に追跡し、これらの結果をウェブベースのバックエンドデータベースに伝達することによって、一定の健康上の目標達成の促進を支援するように、ユーザに対するフィードバックをカスタム化することができる。これらのカスタム化されたフィードバックは、多くの方法で使用可能である。例えば、一定の使用パターン(例えば、最初に喫煙から移行した後に強い欲求を防止するため充分なニコチン投与を与える、又はニコチン停止までの漸減の計画に従って新たな最小ニコチン量を投与する)が達成された場合に、ユーザのニコチン投与パターンを強化し得る仮想クレジット又は実際の金銭的な報酬を与えることができる。
実施例1:空気流量、電流、加熱時間、及びヒータ要素の厚さの変化が、プロピレングリコール調合物から発生させたエアロゾルの粒径に及ぼす影響
[00336] この実施例では、特定のパラメータ(すなわち空気流量、ヒータ要素に対する電流、及びヒータ要素の厚さ)の変化が、本明細書に記載したようなニコチン送達デバイスのコンポーネント及び/又はパラメータを備えるように設計された試験装置によって発生されるエアロゾル粒径に、どのように影響するかについて記載する。図26は試験装置全体の概略を示し、図27は試験装置において用いられる試験気道の代替的な図(alternates view)を示す。試験台は、デルリン(底部)のブロックと透明なプレキシガラス(上部)のシートとの間に生成された気道を有し、真鍮の側部を用いてヒータ要素を留めると共にヒータ要素との電気的接触を与える。ヒータ要素は、厚さが可変の(0.0005インチ(約0.013mm)又は0.001インチ(約0.025mm))ステンレス鋼ホイルであり、エアロゾル発生に用いる調合物は、プロピレングリコールから成る。図27Aは上面図を示し、空気流(2702a)が入口(2704a)に入っている。薬剤を堆積するための孔(2706a)が設けられ、ホイルが図示されている(2708a)。真鍮の接点(2710a)が設けられている。デバイスの長さは6インチ(約152.4mm)であり、幅は2.25インチ(約57.15mm)である。図27Bは、入口(2704b)、ホイル(2708b)、真鍮の電気接点(2710b)、及び出口(2712b)の側面図を示す。図27Cは、ホイル(2708c)及び(2712c)を示し、端面図である。図27Dは等角図を示す。表2は、ヒータ要素の厚さ、空気流量、電流、及び加熱時間の変更が、粒径の分布に対して与える結果を示す。表2の結果に基づき、空気流量を増大させると、他のパラメータを一定に保った場合、粒径(PSD)が小さくなる。
[00337] この実施例では、特定のパラメータ(すなわち空気流量、及びヒータ要素に対する電流)の変化が、実施例1に記載したような試験装置によって10%ニコチン/プロピレングリコール調合物から発生されるエアロゾル粒径に、どのように影響するかについて記載する。表3は、ヒータ要素の厚さ、空気流量、電流、及び加熱時間の変更が、粒径の分布に対して与える結果を示す。表3に示すように、他のパラメータを一定に保ったまま空気流量を変更すると、空気流量が増大するにつれて、平均粒径(PSD)が小さくなる。
[00338] この実施例では、図26及び図27に示し実施例1に記載したような試験装置を用いてPG調合物又は10%ニコチン/PG調合物のいずれかから発生させたエアロゾルの粒径について記載する。この実施例において、ヒータ要素は、巻き数が3.5であり直径が0.10インチ(約2.54mm)のステンレス鋼コイルである。ヒータ要素は2.5アンペアの電流を用いて加熱し、空気流量は4リットル/分(約6.7x10−5m3/s)である。表4に結果を示す。
[00339] この実施例では、2つのブランドの電子タバコ(Finiti及びBLU)のいずれかから発生させたエアロゾルの粒径について記載する。この実施例において、ヒトの呼吸をシミュレートするため、2つのブランドの電子タバコのいずれかから、50mlの体積のエアロゾルを3秒間にわたって吸った。次いで集めたエアロゾルを、14リットル/分(約2.33x10−4m3/s)の流量にセットしたレーザ粒径検出器内に注入した。表5は、2つのブランドの電子タバコから発生させたエアロゾルの粒径を示す。図28は、電子タバコにより生成したエアロゾル対本明細書において提供されるデバイス(デバイス)により生成したエアロゾルの粒径分布の比較を示す。図28に示すように、本明細書において提供されるデバイスにより発生させたエアロゾルの粒径分布は、電子タバコにより発生させたものに対して、粒径が大きい方にシフトしている。
[00340] この実施例では、特定のパラメータ(すなわちバルブ材料及びバイパスオリフィスの直径)の変化が、本明細書において記載したような凝縮エアロゾルを発生させるためのデバイスのコンポーネント及び/又はパラメータを備えるように設計された試験装置によって発生されるエアロゾル粒径に、どのように影響するかについて記載する。図29Aは試験装置全体の概略を示し、図29Bは試験装置において用いられるバルブ(2904a)の内部の図を示す。バルブフラップ(2902b)は3/4インチの直径を有し、バルブの下流のチャネルの直径は、長さが0.375インチ(約9.53mm)であり、幅が0.090インチ(約2.29mm)である。試験台は、一次気道(2906a)、バイパス気道(2908a)、エアロゾル発生チャンバ(2912a)、及び真空ソース(2910a)を有する。エアロゾル発生チャンバはヒータ要素を備えている。バイパス気道への入口は、可変寸法(LxW)のスロットである。表6は、3/4インチ(約19.05mm)の直径のバルブを用い、バルブ材料及びバイパスオリフィス直径を変更した結果を示す。表6に示すように、バルブ材料の種類及びバイパスオリフィスの直径とは無関係に、約2水柱インチの吸入圧(約498Pa)を超えると、一次流量は比較的一定を保つが、バイパス流量は真空圧の上昇と共に増大する。表7は、3/8インチの直径のバルブ、可変寸法のバイパスオリフィスを用い、一次気道の入口のオリフィス寸法を変更した結果を示す。表7に示すように、一次気道のオリフィスのサイズが小さくなると、真空圧の変動、バイパスオリフィスの寸法、又はバルブ材料の変化とは無関係に、一次気道を通る流量が常に減っていく。
[00341] この実施例では、ワイヤコイルを備えたヒータ要素を含むデバイスから発生させたエアロゾルの粒径(PSD)について記載する。このタイプのデバイスの一例を図31A〜図31Dに示す。図31Aは、ENT−100−Aと称するデバイスを示し(2インチ(約50.8mm)の長さ)、一次キャリアガス入口(3112a)、正及び負の真鍮接点(3110a)、入口から一次気道(3112a)まで遠くに位置付けられたコイルを含むヒータ要素(3106a)、ヒータ要素の下流であるが出口(3102a)の前に位置付けられた(配置された)2つのバイパス入口(3104a)を備えている。図31Bは、ENT−100−Bと称するデバイスを示し、これは、ヒータ要素が一次気道(3112b)の入口の近くに移動されたことを除いて、ENT−100−Aと同じである。図31Cは、ENT−100−Cと称するデバイスを示し、これは、ワイヤコイルヒータ要素が、ENT−100−A及びENT−100−Bのコイル位置に対して中間位置に移動されていることを除いて、ENT−100−Aデバイスと同様である。図31A〜図31Cに示したデバイスのいずれも、図31Eに示すような「Aコイル」(3114e)又は「Bコイル」(3116e)と称するワイヤコイルヒータ要素を備えることができる。双方のタイプのヒータ要素のコイルは、内径が0.26インチ(約6.604mm)である。「Aコイル」は、ある長さのコイルに続いてコイルの各端部に直線のリードがあり、これが真鍮接点に接続する。「Bコイル」は、ある長さのコイルを含み、このコイル自体が真鍮接点に接続する。表8〜表12は、図31A〜図31Cに示したデバイスから発生させたエアロゾルの粒径を示す。表8は、「Bコイル」を有するENT−100−Aデバイスを用いて発生させた粒子のPSDを示す。表9は、「Aコイル」を有するENT−100−Bデバイスを用いて発生させた粒子のPSDを示す。表10は、「Bコイル」を有するENT−100−Bデバイスを用いて発生させた粒子のPSDを示す。表11は、「Aコイル」を有するENT−100−Cデバイスを用いて発生させた粒子のPSDを示す。表12は、「Bコイル」を有するENT−100−Cデバイスを用いて発生させた粒子のPSDを示す。
用量=2mg(プロピレングリコール調合物)、電流=3アンペア、時間=1秒
用量=2mg(プロピレングリコール調合物)、時間1秒、電流3.1アンペア
用量=2mg(プロピレングリコール調合物)、時間1秒、電流2.0アンペア
電流は2.0アンペアにセット、1秒、2mg用量(プロピレングリコール調合物)
電流は2.0アンペアにセット、1秒、2mg用量(プロピレングリコール調合物)
[00342] この実施例では、ワイヤを備えたヒータ要素から発生させたエアロゾルの粒径(PSD)について記載する。ワイヤの一端は、ワイヤの別のセグメントを包み、ワイヤの一端がワイヤコイルの中央を通過してワイヤコイルが形成されている。このタイプのヒータ要素の一例を図36〜図38に示す。この実施例では、ヒータ要素は、図31Dに示すデバイス内に挿入されている。図31Dは、ENT−100−Dと称するデバイスを示し、空気を流すための一次通路と、一次通路の壁内に埋め込まれた真鍮接点(+/−)と、この実施例に記載するようなヒータ要素と、を有する。ヒータ要素のワイヤは、直径が0.10インチ(約2.54mm)である。ヒータ要素のワイヤコイルは巻き数が9のコイルを有し、ワイヤコイルの内径は0.032インチ(約0.813mm)である。この実施例では、液体調合物はプロピレングリコールを含み、ヒータ要素のワイヤの端部及び真鍮接点に吸い上げられる。表13は、ヒータ要素を備えたデバイスから発生させたエアロゾルの粒径を示す。表13に示すように、ヒータ要素を備えたデバイスによって発生させたエアロゾルの粒径分布は、ワイヤを加熱するために用いる電流を変更することによる影響を受けない。
ヒータ要素 0.032 10,010直径のワイヤ、巻き数9、中央延出
[00343] この実施例では、図36に示したようなヒータ要素から発生させたエアロゾルの粒径(PSD)について記載する。この実施例では、図37に示すように、ワイヤコイルを真鍮接点に接続するリードが長くなっている。この実施例におけるリードの長さは0.70インチ(約17.78mm)である。ヒータ要素は、図31Dに示すデバイス内に挿入されている。図31Dは、ENT−100−Dと称するデバイスを示し、空気を流すための一次通路と、一次通路の壁内に埋め込まれた真鍮接点(+/−)と、この実施例に記載するようなヒータ要素と、を有する。一部の例では、入口の直径は0.060インチから0.070インチ、0.071インチ、又は0.041インチ(約1.524mmから1.78mm、1.80mm、又は1.04mmの範囲)まで変動する。ヒータ要素のワイヤは、直径が0.10インチ(約0.254mm)である。ヒータ要素のワイヤコイルは巻き数が減り、ワイヤコイルの内径は0.032インチ(約0.813mm)である。この実施例では、液体調合物はプロピレングリコールを含み、ヒータ要素のワイヤの端部及び真鍮接点に吸い上げられる。表14は、ヒータ要素を備えるデバイスから発生させたエアロゾルの粒径を示す。表14に示すように、ヒータ要素を備えるデバイスによって発生させたエアロゾルの粒径分布は、ワイヤを加熱するために用いる電流を変更することによる影響を受けない。また、表14は、ENT−100−Dデバイスにおいて気道の構成を変更することによる影響も示している。表14に示すように、ヒータ要素の下流に図32Eに示す気道を追加することでENT−100−Dデバイスの気道の構成を変更すると(表14においてMARK V加算器と示す)、PSDが約1から約2μmの粒子が生成される。
[00344] この実施例では、図36に記載したようなヒータ要素から発生させたエアロゾルの粒径(PSD)について記載する。この実施例において、ワイヤコイルを真鍮接点に接続するリードの長さは0.30インチ(約0.762mm)である。ヒータ要素は、図31Dに示すデバイス内に挿入されている。図31Dは、ENT−100−Dと称するデバイスを示し、空気を流すための一次通路と、一次通路の壁内に埋め込まれた真鍮接点(+/−)と、この実施例に記載するようなヒータ要素と、を有する。ヒータ要素のワイヤは、直径が0.10インチ(約2.54mm)である。ヒータ要素のワイヤコイルは実施例8に比べて巻き数が増え、ワイヤコイルの内径は0.032インチ(約0.813mm)である。この実施例では、液体調合物はプロピレングリコールを含み、ヒータ要素のワイヤの端部及び真鍮接点に吸い上げられる。調合物の用量は2mgである。表15は、この実施例で記載したデバイスから発生させたエアロゾルの粒径を示す。表15に示すように、このデバイスによって発生させたエアロゾルの粒径分布は、ワイヤを加熱するために用いる電流を変更することによる影響を受けない。
[00345] この実施例では、図36に示したようなヒータ要素を備えたデバイスから発生させたエアロゾルの粒径(PSD)について記載する。この実施例において、ヒータ要素は、図31Dに示すデバイス内に挿入されている。図31Dは、ENT−100−Dと称するデバイスを示し、空気を流すための一次通路と、一次通路の壁内に埋め込まれた真鍮接点(+/−)と、この実施例に記載するようなヒータ要素と、を有する。ヒータ要素のワイヤは、直径が0.10インチ(約2.54mm)である。ヒータ要素のワイヤコイルは、内径が0.032インチ(約0.813mm)である。この実施例では、液体調合物はプロピレングリコールを含み、ヒータ要素のワイヤの端部及び真鍮接点に吸い上げられる。この実施例における調合物の用量は2mgである。表16は、この実施例で記載したヒータ要素を備えるデバイスから発生させたエアロゾルの粒径を示す。表16に示すように、ヒータ要素を有するデバイスによって発生させたエアロゾルの粒径分布は、ワイヤを加熱するために用いる電流を変更することによる影響を受けない。また、表16に示すように、ヒータ要素の下流に図33に示す気道を追加することでENT−100−Dデバイスの気道構成を変更すると(表15においてMARK VI加算器と示す)、PSDが約1から約2μmの粒子が生成され、これは、MARK VI加算器なしで発生させた粒子のPSDと一致する。MARK VI加算器は、内径が0.25インチ(約6.35mm)の一次気道を備え、これは細くなって、内径が0.086インチ(約2.18mm)及び外径が0.106インチ(約2.69mm)の気道になる。
用量=2mg、電流2アンペア、時間1秒
[00346] この実施例では、図33に示す気道構成を備えたデバイスにより発生させた凝縮エアロゾルの粒径(PSD)を試験する。このデバイスは、内径が0.25インチ(約6.35mm)の一次気道を備え、これは細くなって、内径が0.086インチ(約2.18mm)及び外径が0.106インチ(約2.69mm)の気道になる。気道構成は、ワイヤコイルを備えたヒータ要素に結合され、ヒータ要素は、一次気道が細くなる箇所の上流でプロピレングリコールを含む液体調合物を気化させる。気化した調合物は細くなった気道に入り、凝縮して粒子になる。細くなった一次気道は、蒸気を所望のサイズの粒子(例えばMMADが約1から約5μm)に凝縮するのに適した流量でキャリアガス(例えば空気)に気化調合物を運ぶように設計されている。この実施例では、細くなった一次気道は、内径が0.25インチ(約6.35mm)の広い下流気道内で開口し、凝縮した粒子は、一次気道の壁に位置付けられた(配置された)入口から広くなった一次移動へと入ってくるバイパスキャリアガス(例えば空気)と混合される。入口から入ってくるキャリアガスは、一次気道を包含する二次筐体の壁にあるバイパス入口から供給される。この実施例では、バイパスガスの流量(B流量)の変動が、凝縮したものPSDに対して与える影響について調べる。表17に結果を示す。表17に示すように、異なるB流量はPSDに対して影響を与えない。更に、各B流量におけるPSDは1から3μMの間である。表18は、二次筐体のバイパス入口を通るバイパスキャリアガスの流れを制限することがPSDに対して与える影響を示す。バイパス入口を通るバイパスガスの流れは、バルブを用いることによって、又はオリフィスの幾何学的形状を変える(すなわち異なる寸法のスロットを形成する)ことによって制限される。表18に示すように、バイパスガスの流れを制御するためのバルブ又はスロットの使用は、約1から約5μmのPSDの粒子を生成するために効果的である。
[00347] この実施例では、図31Dに示したようなENT−100−Dデバイスにより発生させた凝縮エアロゾルの粒径(PSD)に対する重力の影響について試験する。ENT−100−Dデバイスに、2mgの液体プロピレングリコール調合物を投入し、デバイスの使用中にデバイスを回転させる。デバイスは、安定したベースライン位置から、あらゆる次元に90度回転させる。各回転において粒径を測定したところ、変化は見られない。この結果、デバイスは、デバイスの空間内での向きとは無関係に、一定の粒径の粒子を生成する。
研究の母集団及びサンプルサイズ
研究の制約
併用する薬物
食物及び飲料
[00356] 被験者は、拘束期間前の48時間、及び拘束時間中のいかなる時点でも、激しい運動を行わない。
研究実行期間
研究製剤
製剤投与/実験セッション
薬物動態サンプル収集、パラメータ、及び分析:
[00380] パート1及びパート2の双方において製剤を投与した後、患者報告結果(PRO:patient-reported outcome)測定によって、喫煙衝動、嫌悪/忍容度、呼吸器の感覚、及び主観的な効果を評価する。
[00382] 研究のパート1に入る前に、病歴、バイタルサイン、尿中薬物及びアルコールスクリーン、並びに妊娠検査(女性のみ)を実行する。パート1のチェックイン評価には、バイタルサイン、尿中薬物及びアルコールスクリーン、並びに妊娠検査(女性のみ)が含まれる。
[00386] パート1及びパート2の双方について、肺活量、パルスオキシメトリ、及び吐き出されるCOの値を、被験者及び時点ごとにリスト化する。各査定における投与前と投与後との差を、記述統計学を用いて時点ごとに集計し、適切な統計的方法を用いて分析する。
[00388] エアロゾルはeNT−100吸入器の内部で生成される。この吸入器自体は、試験物質(test article)を試験の被験者から見えないようにするために用いられる小さい円筒形のプラスチック製筐体の内部にある。試験の被験者は、図示したステンレス鋼のマウスピース上でスライドするプラスチック製チューブから吸入する。エアロゾル発生吸入器の内部には小さいヒータ要素があり、これを用いて、1.4から2.5ミクロンのエアロゾル粒子が得られる流量条件のもとでニコチン溶液を気化する。ニコチン吸入器は更に、ニコチン溶液のある用量をヒータ要素上に量り分けるための容積移送式ポンプを備えている。
Claims (9)
- 液体から凝縮エアロゾルを発生させるためのデバイスであって、
入口及び出口を有するハウジングと、
液体調合物を含む容器と、
ヒータ要素を備える前記ハウジング内の通路であって、前記通路内にはチューブが配置され、前記ヒータ要素が前記通路において前記入口と前記出口との間に配置され、前記チューブが、前記容器に接続されるとともに前記容器から前記ヒータ要素に前記液体を送出するように構成され、前記通路が、前記デバイスにおいて、1μmから5μmの空気動力学的中央粒子径(MMAD)を有する凝縮エアロゾルを生成するように構成される、通路と、
前記容器と流体連通する容積移送式ポンプと、
前記出口(4046)と前記ヒータ要素(110)との間で前記通路に配置されたバッフル(4402)と、を備え、
前記容積移送式ポンプは、蠕動ポンプを含み、
前記バッフル(4402)が、5μmより大きいMMADを有する粒子の流れを阻害する、デバイス。 - 前記ヒータ要素が、ワイヤコイルを備える、請求項1に記載のデバイス。
- 前記容積移送式ポンプが、前記液体調合物を含む前記液体調合物を前記ヒータ要素にポンプで供給するように構成されている、請求項1に記載のデバイス。
- 前記通路が、0.20cmから1.3cmの内径を有する、請求項1から3の何れか一項に記載のデバイス。
- 前記チューブが、毛細管である、請求項1に記載のデバイス。
- 前記チューブが、第2のヒータ要素を備える、請求項1から5の何れか一項に記載のデバイス。
- 249Paから3738Paの真空の範囲で、前記通路を通るガスの流量が、20リットル/分から80リットル/分の範囲である、請求項1から6の何れか一項に記載のデバイス。
- 前記デバイスの前記入口と前記出口の間の流れ抵抗が、0.05から0.15sqrt(cm−H2O)/LPMの範囲である、請求項1から7の何れか一項に記載のデバイス。
- 吸入を検出するためのセンサを更に備える、請求項1から8の何れか一項に記載のデバイス。
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DE202013105420U9 (de) | 2014-06-12 |
PL2925395T3 (pl) | 2019-08-30 |
EP2925395B1 (en) | 2019-03-06 |
GB2508520B (en) | 2016-03-02 |
AU2013352004B2 (en) | 2019-02-14 |
KR102169734B1 (ko) | 2020-10-26 |
AU2013352004A1 (en) | 2015-05-28 |
MX2015006683A (es) | 2016-03-08 |
EP2925395A1 (en) | 2015-10-07 |
CA2890204C (en) | 2022-04-05 |
JP6429788B2 (ja) | 2018-11-28 |
HK1215799A1 (zh) | 2016-09-15 |
CN104955508A (zh) | 2015-09-30 |
JP2016501588A (ja) | 2016-01-21 |
GB2508520A (en) | 2014-06-04 |
ZA201503522B (en) | 2019-07-31 |
CN111729161A (zh) | 2020-10-02 |
EP2925395A4 (en) | 2016-06-15 |
IL238641A0 (en) | 2015-06-30 |
GB201321023D0 (en) | 2014-01-15 |
WO2014085719A1 (en) | 2014-06-05 |
DE202013105420U1 (de) | 2014-04-03 |
CN204147375U (zh) | 2015-02-11 |
CA2890204A1 (en) | 2014-06-05 |
KR20150095709A (ko) | 2015-08-21 |
SG11201504008PA (en) | 2015-06-29 |
US20140190496A1 (en) | 2014-07-10 |
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