JP6886925B2 - 分離可能なマイクロニードルを有する薬剤送達デバイス - Google Patents
分離可能なマイクロニードルを有する薬剤送達デバイス Download PDFInfo
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- JP6886925B2 JP6886925B2 JP2017554327A JP2017554327A JP6886925B2 JP 6886925 B2 JP6886925 B2 JP 6886925B2 JP 2017554327 A JP2017554327 A JP 2017554327A JP 2017554327 A JP2017554327 A JP 2017554327A JP 6886925 B2 JP6886925 B2 JP 6886925B2
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Description
この出願は、参照により本明細書に組み込まれる2015年4月17日に出願された米国仮出願62/149,043の優先権を主張する。
マイクロニードルアレイは、ベース基板の表面から突出する2つ以上のマイクロニードルを含む。語句「ベース基板(base substrate)」及び用語「基板(substrate)」は、本明細書において入れ替え可能に用いられる。各マイクロニードルは、直接的に又は間接的に1つ又は複数の既定の折れる領域を介して、ベース基板に取り付けられる近位端部と、鋭利な及び生物学的組織を貫通するのに効果的な遠位先端部とを有する。マイクロニードルは、近位端部と遠位端部との間にテーパ形状の側壁を有し得る。
実施形態において、薬剤送達デバイスは既定の折れる領域を含む。基板及び/又は1つ又は複数のマイクロニードルは既定の折れる領域を含む。実施形態において、この領域は、マイクロニードルと基板との間の脆い境界面であるとみなされ得る。既定の折れる領域は、マイクロニードル又はマイクロニードル及び基板の一部分が所望の位置で又は所望の位置の近くで分離する可能性を増大し得る。いくつかの実施形態において、既定の折れる領域は、マイクロニードル又はマイクロニードル及び基板の一部分が所望の位置で又は所望の位置の近くで分離することを確実にする。
本明細書で用いられるような語句「生物学的組織」は、一般に任意の人又は哺乳類の組織を含む。生物学的組織は、治療又は予防を必要とする人又は他の哺乳類の皮膚又は粘膜組織であり得る。本デバイス及び方法はまた、他の生物学的組織及び他の動物に適合され得ることが想定される。
例えば、図3Aは、基板310及び生物学的組織表面330を貫通したマイクロニードル320を含むデバイス300の一実施形態を示す。マイクロニードル320の基板310からの分離に際して、分離されたマイクロニードル340は、完全に組織表面330の下に位置される。さらなる例として、図3Bは、基板360及び生物学的組織表面380を貫通するマイクロニードル320を含むデバイス350の別の実施形態を示す。マイクロニードル320の基板360からの分離に際して、分離されたマイクロニードル390の遠位部分は組織表面380の下に位置され、及び近位部分は組織表面から突出する。別の言い方をすると、分離されたマイクロニードル390は、部分的に生物学的組織に埋め込まれる。
実施形態において、本明細書で提供される薬剤送達デバイスは、有利には薬剤送達デバイスに適用される力に応答するように構成される。一実施形態において、力は、マイクロニードルのアレイの1つ又は複数のマイクロニードルを用いて生物学的組織表面を貫通するのに効果的である。別の実施形態において、力は、マイクロニードルのアレイの1つ又は複数のマイクロニードルを用いて生物学的組織表面を貫通し、及びマイクロニードルのアレイの1つ又は複数のマイクロニードルを基板から分離するのに効果的である。
実施形態において、本明細書において提供される薬剤送達デバイスは、ハウジングを含む。基板及び支持層のうちの少なくとも1つは、任意の手法においてハウジングと連携され得る。例えば、基板又は支持層のうちの少なくとも1つは、ハウジング内に配置され得る。さらなる例として、基板及び支持層のうちの少なくとも1つは、当技術分野において周知な任意の手段によって、ハウジング内又はハウジング上に固定可能又は移動可能に取り付けられ得る。例えば、基板及び/又は支持層は、移動可能に取り付けられる場合、トラック、中心軸、又はその組合せ上に取り付けられ得る。
実施形態において、薬剤送達デバイスは、マイクロニードルが少なくとも部分的に生物学的組織内に挿入された後、マイクロニードルからの及び生物学的組織内への薬剤の放出の速度の変化をトリガーするためのシステムを含む。薬剤送達デバイスからの薬剤の放出は、配置時又は配置後、徐々に又は特定の時間において起こる事象をトリガーすることによって達成され得る。
一実施形態において、薬剤の放出をトリガーするためのシステムは、生体体液との接触に基づいて、マイクロニードルの第2の部分よりも速い速度で生体腐食するように構成されたマイクロニードルの第1の部分を含む。例えば、透過性変化は、組織液(間質液など)にマイクロニードルが貫通することを可能にし、結果として、放散を介して周囲の組織内へのマイクロニードルからの薬剤の放出を可能にし得る。また、浸透圧における変化は、薬剤の放出を引き起こし又は誘発し得る。
一実施形態において、トリガーするためのシステムは、少なくとも1つの方向内で及び/又は既定の時間の間、マイクロニードルからの薬剤の放出を妨害するために、マイクロニードルの少なくとも部分内又は部分上に配置され得るバリアである。一実施形態において、バリアは、(i)注入時又は注入後の非連続な時間の薬剤放出、(ii)薬剤が放出されるところのマイクロニードルの領域の制御、若しくは(iii)その組合せを可能にするように構成される。用語「バリア」及び語句「バリア材料」は、本明細書において入れ替え可能に用いられる。
支持層は、接着剤を含む当技術分野において周知な任意の手段によって、基板に付着され得る。一実施形態において、付着層は、基板に支持層を付着するために用いられる。
本明細書で用いられるように、語句「組織表面を貫通する(penetrate a tissue surface)」又は用語「貫通する(penetrate)」若しくは「貫通(penetration)」は、生物学的組織内への、マイクロニードルの少なくとも先端又は遠位端部を含むマイクロニードルのアレイのマイクロニードルの少なくとも50%及び典型的に実質的にすべての挿入を、意味する。好ましい実施形態において、マイクロニードルの少なくとも先端部は、実行可能な表皮内に存在し又は実行可能な表皮を通り抜けるように、「貫通(penetration)」はヒト患者の皮膚の角質層を貫通することを含む。
広範囲に有効な物質は、本マイクロニードル及び方法を用いた生物学的組織への送達のために形成され得る。本明細書で用いられるように、用語「対象の物質」は、生物学的組織内に取り入れるのに望ましい、有効医薬成分、アレルゲン、ビタミン、美容用薬品、薬用化粧品、診断用薬品、標識(例えば、着色された染料又は放射性物質の染料又は標識)、及び他の材料を含む。「対象の物質」は、ときには本明細書において、「活性剤」又は「API」又は「薬剤」と言及される。
マトリックス材料は、マイクロニードル及び基板のバルクを形成する。それは、典型的に、単独に又は他の材料との組合せにおいて、生体適合性の高分子材料を含む。実施形態において、少なくともマイクロニードルのマトリックス材料は水溶性である。ある特定の好ましい実施形態において、マトリックス材料は、ポリビニルアルコール、デキストラン、カルボキシメチルセルロース、マルトデキストリン、スクロース、トレハロース、及び他の糖の1つ又はそれらの組合せを含む。本明細書で用いられるように、用語「マトリックス材料」及び「賦形剤」は、マイクロニードル及び基板の乾燥及び形成の間に揮発されない任意の賦形剤について言及される場合、入れ替え可能に用いられる。
マイクロニードルのアレイは、当技術分野において周知な任意の方法で作られ得る。例えば、マイクロニードルのアレイは、有利には高度に拡張可能な成形プロセスを用いて作られ得る。プロセスは、適切に流体化された材料を用いて適切な型を充填すること、マイクロニードル、含まれる場合には既定の折れる領域及びベース基板を形成するために流体化された材料を乾燥すること、並びに次いで、形成された部分を型から取り除くことを含み得る。これらの充填する及び乾燥するステップは、当技術分野において「鋳造」として言及され得る。
マイクロニードルアレイは、以下のように製造された。第1の溶液(リン酸カリウム緩衝液において、10重量%のスクロース、1重量%のカルボキシメチルセルロースをもつ)が、ポリジメチルシロキサン(PDMS)マイクロニードル型内に真空下で鋳造され、及びマイクロニードルを形成するために、10分間周囲状況下で乾燥された。次いで、第2の溶液(リン酸カリウム緩衝液において、10重量%のスクロース、1重量%のカルボキシメチルセルロースをもつ)が、PDMSマイクロニードル型内に真空下で鋳造され、及び基板/基層を形成するために、35℃で一晩中乾燥された。次いで、付着裏側(支持層)(3M1503褐色片面コートポリエチレン医療テープ)が、マイクロニードルパッチを形成するために、マイクロニードルアレイの基部に取り付けられた。マイクロニードルアレイは、次いで型から取り除かれ、及び箔パウチ内に乾燥剤とともに包装された。
実施例1において作られたマイクロニードルアレイが、皮膚内にマイクロニードルを挿入するために、切除されたブタの皮膚に加えられた。次いで、パッチを、組織表面に対するパッチの固定を保つように下向きの力を持続しながら、横方向に(水平に、皮膚の表面と平行に)引っ張った。パッチを次いで皮膚から引き離し、撮像した。親水性染料(ゲンチアナバイオレット、1%)が、次いでマイクロニードル挿入の区域でブタの皮膚に加えられた。染料が、30秒の間ブタの皮膚の表面上にとどまることが可能にされ、次いでそれはイソプロパノール布巾を用いて拭き取られた。次いで、ブタの皮膚の表面が撮像され、及び染色のために評価された。
別のマイクロニードルアレイが、以下のように製造された。第1の溶液(リン酸カリウム緩衝液において、10重量%のスクロース、1重量%のカルボキシメチルセルロース、及び0.1%のスルホローダミンB(赤色色素)をもつ)が、ポリジメチルシロキサン(PDMS)マイクロニードル型内に真空下で鋳造され、及びマイクロニードルを形成するために、40℃で30分間乾燥された。次いで、第2の液体(2部分のポリウレタン高ジュロメーターエラストマー(60D液体ウレタン、フォルシュポリマー社)の混合物が、PDMSマイクロニードル型内に真空下で鋳造され、及びテーパ形状の基板/基層を形成するために、一晩中硬化させた。次いで、付着裏側(支持層)(3M1503褐色片面コートポリエチレン医療テープ)が、マイクロニードルパッチを形成するために、マイクロニードルアレイの基部に取り付けられた。マイクロニードルアレイは、次いで型から取り除かれ、及び箔パウチ内に乾燥剤とともに包装された。
実施例3において作られたマイクロニードルアレイが、皮膚内にマイクロニードルを挿入するために、切除されたブタの皮膚に加えられた。次いで、パッチを、組織表面に対するパッチの固定を保つように下向きの力を持続しながら、横方向に(水平に、皮膚の表面と平行に)引っ張った。マイクロニードルに入れられた染料が皮膚内に放出され、第2の染色は実行されなかった。次いで、ブタの皮膚の表面が撮像され、及び染色のために評価された。パッチを皮膚から引き離し、また撮像した。
Claims (16)
- 押下可能部分を有するハウジングと、
マイクロニードル面及び対向する裏面を有する基板と、
前記基板の前記マイクロニードル面から突出するマイクロニードルのアレイであって、前記マイクロニードルが薬剤を含む、マイクロニードルのアレイと、
前記基板の前記対向する裏面上に配置され、及び前記ハウジング内に移動可能に取り付けられる支持層と、を備え、
前記押下可能部分が、押下に際して、
(i)組織内に前記マイクロニードルのアレイを挿入するのに効果的である、前記マイクロニードルのアレイへの第1の力と、(ii)前記マイクロニードルのアレイを前記基板から分離するのに効果的である、前記支持層及び基板のうちの少なくとも1つへの第2の力とをもたらすインプット力を適用する又は作動させるように構成され、前記第2の力が剪断力である、薬剤送達デバイス。 - 前記マイクロニードルが、水溶性、生体分解性又は他の生体分解可能な材料を含み、その中で前記薬剤が分散され及び/又はその上で前記薬剤が被覆される、請求項1に記載の薬剤送達デバイス。
- 前記第2の力が、回転性の剪断力又は横方向の剪断力である、請求項1に記載の薬剤送達デバイス。
- 前記押下可能部分による作動に際して、前記第2の力を加えるように構成された弾性歪みエネルギーを格納するためのデバイスをさらに含む、請求項1〜3のいずれか1項に記載の薬剤送達デバイス。
- 前記弾性歪みエネルギーを格納するためのデバイスがばねである、請求項4に記載の薬剤送達デバイス。
- 前記押下可能部分による作動に際して、前記第2の力を加えるように構成された電子的要素をさらに含む、請求項1〜3のいずれか1項に記載の薬剤送達デバイス。
- 前記電子的要素が、磁界及び電界のうちの少なくとも1つにより前記第2の力を生成する、請求項6に記載の薬剤送達デバイス。
- 前記押下可能部分及び前記支持層のうちの少なくとも1つが、前記押下可能部分の押下に際して、前記基板に回転性の剪断力を加えるように構成されたねじ状の又はらせん状の部分を含む、請求項1〜3のいずれか1項に記載の薬剤送達デバイス。
- 前記薬剤送達デバイスが、前記押下可能部分の押下に際して、前記押下可能部分及び前記支持層が互いに接触することを可能にするように構成される、請求項1〜3のいずれか1項に記載の薬剤送達デバイス。
- 前記支持層が、前記押下可能部分の押下に際して、前記押下可能部分と接触するように構成された実質的に傾斜した表面を含む、請求項9に記載の薬剤送達デバイス。
- 前記押下可能部分が、前記押下可能部分の押下に際して、前記支持層と接触するように構成された実質的に傾斜した表面を含む、請求項9に記載の薬剤送達デバイス。
- 前記マイクロニードルのアレイの1つ又は複数のマイクロニードルが、前記第2の力の適用に際して、前記1つ又は複数のマイクロニードルが前記基板から分離するように構成される少なくとも1つの特徴を含む、請求項1〜3のいずれか1項に記載の薬剤送達デバイス。
- 前記少なくとも1つの特徴が、前記マイクロニードルのアレイの1つ若しくは複数のマイクロニードル及び/又は前記マイクロニードルのアレイの前記1つ若しくは複数のマイクロニードルのそれぞれに関して位置される前記基板の近位端部に、既定の折れる領域を含む、請求項12に記載の薬剤送達デバイス。
- 前記既定の折れる領域が、実質的に細い部分、壊れやすい部分、細かい切り目を付けられた部分、刻み目を付けられた部分、異なる材料の境界面、異方性の機械的な特性を有する1つ若しくは複数の材料、又はそれらの組合せを含む、請求項13に記載の薬剤送達デバイス。
- 前記押下可能部分への手動の既定の力の適用に際して、前記押下可能部分が、前記デバイス内に歪みエネルギーをインプットするように構成され、及び前記デバイスが、前記第2の力としての前記歪みエネルギーを放出するように構成される、請求項1に記載の薬剤送達デバイス。
- 前記第2の力が剪断力であり、前記インプット力が前記剪断力より小さく、及び前記剪断力が、前記デバイス内に格納されたエネルギーの放出によって少なくとも部分的に影響を受ける、請求項1に記載の薬剤送達デバイス。
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