JP2006328083A - キャリア流体内への分子の送達のための微細加工されたデバイス - Google Patents
キャリア流体内への分子の送達のための微細加工されたデバイス Download PDFInfo
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Abstract
【解決手段】キャリア流体内への分子の制御放出のための装置であって、以下:(i)放出のための該分子を収容する複数のリザーバを有する、マイクロチップデバイス、および(ii)キャリア流体が流れ得る構造を備える混合チャンバであって、該混合チャンバは、該キャリア流体の流れに関して、該マイクロチップデバイスに隣接するかまたは該マイクロチップデバイスの下流に位置する、混合チャンバ、を備え、ここで、該分子が、該リザーバの1つ以上からの該分子の放出に続いて、該キャリア流体と混合される、装置。
【選択図】なし
Description
本発明は、一般に、キャリア流体中への化学分子の制御送達のための、小型化されたデバイスに関する。
キャリア流体を介する、ある部位への分子の送達のための装置および方法が提供される。この装置は、放出のための分子を収容するリザーバを有する、マイクロチップデバイスを備える。この装置および方法は、分子の能動的かまたは受動的な制御放出を提供する。このマイクロチップデバイスは、以下を備える:(1)基板、(2)放出のための分子を収容する、この基板における少なくとも2つのリザーバ、および(3)このリザーバの上かまたはこのリザーバの一部の内部に位置し、そして分子を覆うリザーバキャップであって、これによって、このリザーバキャップの崩壊または破裂によってかまたはその際に、拡散によってこのデバイスから分子が制御可能に放出される、リザーバキャップ。単一のマイクロチップのリザーバの各々は、異なる分子、ならびに/または異なる量および濃度を収容し得、独立して放出され得る。充填されたリザーバは、受動的にかまたは能動的に崩壊する材料でキャップされ得る。受動放出リザーバキャップは、分子を経時的にこのリザーバの外へと受動的に拡散させる材料を使用して、作製され得る。能動放出リザーバキャップは、電気エネルギー、機械的エネルギー、または熱エネルギーの適用の際に崩壊する材料を使用して、作製され得る。能動デバイスからの放出は、予めプログラムされたマイクロプロセッサ、遠隔操作、またはバイオセンサによって、制御され得る。
本発明は、さらに、以下の手段を提供する。
(項目1) 分子の制御放出のための装置であって、以下:
(i)放出のための該分子を収容する複数のリザーバを有する、マイクロチップデバイス、および
(ii)キャリア流体の容器、
を備え、ここで、該分子が、該リザーバの該分子の放出に続いて、該キャリア流体と混合される、装置。
(項目2) 前記容器と流体連絡する混合チャンバをさらに備え、前記分子は、該混合チャンバ内で前記キャリア流体と混合される、項目1に記載の装置。
(項目3) ミキサーをさらに備える、項目1に記載の装置。
(項目4) ポンプをさらに備える、項目1に記載の装置。
(項目5) 前記分子が、薬物分子であり、そして前記キャリア流体が、静脈内投与のために生理学的に受容可能な流体である、項目1に記載の装置。
(項目6) 前記マイクロチップデバイスの前記リザーバが、リザーバキャップによって覆われ、該リザーバキャップが、前記分子を前記キャリア流体中にエキソビボで放出するように、選択的に破裂または崩壊し得る、項目5に記載の装置。
(項目7) 前記キャリア流体が、水、生理食塩水、血漿、全血、および糖溶液からなる群より選択される、項目5に記載の装置。
(項目8) 前記容器がIVバッグまたは瓶である、項目5に記載の装置。
(項目9) 混合チャンバをさらに備える、項目5に記載の装置。
(項目10) 前記混合チャンバから延びる可撓性中空管をさらに備える、項目9に記載の装置。
(項目11) 前記リザーバ内の前記分子が、前記キャリア流体との接触の前には、安定な乾燥形態である、項目1に記載の装置。
(項目12) 患者への後の投与のためのキャリア流体への薬物の送達のための装置であって、以下:
(i)放出のための分子を収容する複数のリザーバを有する、マイクロチップデバイス、および
(ii)混合チャンバ、
を備え、ここで、該分子が、該リザーバからの該分子の放出に続いて、該混合チャンバ内の該キャリア流体と混合される、装置。
(項目13) IVバッグまたは瓶をさらに備える、項目12に記載の装置。
(項目14) 前記混合チャンバがIVバッグまたは瓶である、項目12に記載の装置。
(項目15) 前記キャリア流体が、水、生理食塩水、血漿、全血、および糖溶液からなる群より選択される、項目12に記載の装置。
(項目16) 前記混合チャンバが、出口を備え、該出口から、キャリア流体と薬物との混合物が流れ、そしてここで、中空管が、患者への静脈内接続のために、該出口に接続される、項目12に記載の装置。
(項目17) 2つ以上のマイクロチップデバイスを備える、項目12に記載の装置。
(項目18) 前記混合チャンバが、1つ以上の交換可能なカートリッジを受容するよう適合されたコンソール内に提供され、該カートリッジの各々が、少なくとも1つのマイクロチップデバイスを収容する、項目12に記載の装置。
(項目19) 前記マイクロチップデバイスと通信する電気制御システムをさらに備える、項目12に記載の装置。
(項目20) 前記通信が無線である、項目19に記載の装置。
(項目21) 前記マイクロチップデバイスに収容されている前記薬物を同定するラベルを有する、項目12に記載の装置。
(項目22) 前記ラベルが、電子的に読み取り可能な形態の情報を含む、項目21に記載の装置。
(項目23) 前記混合チャンバが、計量された用量の呼吸器に組み込まれる、項目12に記載の装置。
(項目24) インビボでの分子の放出のためのデバイスであって、以下:
医療ステント、および
放出のための該分子を収容する複数のリザーバを有する、マイクロチップデバイス、
を備え、ここで、該マイクロチップデバイスが、該医療ステントに組み込まれるか、または該医療ステントの表面に取り付けられる、デバイス。
(項目25) インビボで薬物分子を放出するためのデバイスであって、以下:
微細加工された複数のリザーバを有する医療ステントであって、該リザーバが、放出のための該分子を収容する、医療ステント、
を備える、デバイス。
(項目26) 前記ステントが心臓血管ステントである、項目25に記載のデバイス。
(項目27) 前記薬物が抗再狭窄剤である、項目25に記載のデバイス。
(項目28) 芳香性分子を放出するための装置であって、以下:
放出のための該芳香性分子を収容する複数のリザーバを有する、マイクロチップデバイス、および
キャリア流体の容器、
を備える、装置。
(項目29) 飲料に分子を添加するためのシステムであって、以下:
放出のための芳香性分子を収容する複数のリザーバを有するマイクロチップデバイス、および
飲料または飲料ベースの容器
を備える、システム。
(項目30) 分子の制御送達のためのデバイスであって、以下:
(i)複数のリザーバを有するマイクロチップデバイスであって、該リザーバが、該分子を収容し、そしてリザーバキャップによって密封される、マイクロチップデバイス、および
(ii)ポンプを備える移植された送達システム、
を備え、ここで、該マイクロチップデバイスの該リザーバが、インビボで、送達システムにおいて流体の流れに選択的に曝露され、そしてここで、該分子が、該送達システムにおいて流体が流れる間に、該リザーバキャップの崩壊の際に、該リザーバから放出される、デバイス。
(項目31) ある部位へと分子を送達するための方法であって、以下:
(a)項目1に記載の装置を提供する工程;
(b)前記マイクロチップデバイスの前記リザーバを、前記キャリア流体に選択的に曝露する工程であって、これによって、前記分子を該リザーバから放出させ、そして該キャリア流体と混合して、分子/キャリア流体混合物を形成する、工程、ならびに
(c)該分子/キャリア流体混合物を該部位に移送する工程、
を包含する、方法。
(項目32) 前記部位が、ヒトまたは動物であり、そしてここで、前記分子が、薬物分子である、項目31に記載の方法。
(項目33) 前記移送する工程が、静脈内投与による、項目32に記載の方法。
(項目34) 前記キャリア流体が、水、生理食塩水、血漿、全血、および糖溶液からなる群より選択される、項目33に記載の方法。
(項目35) ある部位へと分子を送達するための方法であって、以下:
(a)項目12に記載の装置を提供する工程;
(b)前記マイクロチップデバイスの前記リザーバを、前記キャリア流体に選択的に曝露する工程であって、これによって、前記分子を該リザーバから放出させ、そして該キャリア流体と混合して、分子/キャリア流体混合物を形成する、工程、ならびに
(c)該分子/キャリア流体混合物を該部位に移送する工程、
を包含する、方法。
(項目36) 前記部位が、ヒトまたは動物であり、そしてここで、前記分子が、薬物分子である、項目35に記載の方法。
(項目37) 前記移送する工程が、静脈内投与による、項目36に記載の方法。
(項目38) 前記キャリア流体が、水、生理食塩水、血漿、全血、および糖溶液からなる群より選択される、項目37に記載の方法。
(I.送達装置およびシステム)
この送達システムは、1つ以上のマイクロチップデバイス(例えば、本明細書中およびSantiniらに付与された米国特許第5,797,898号および米国特許第6,123,861号に記載のマイクロチップデバイス)。同特許の全体を参考のため援用する。)を含む。例えば、図1を参照されたい。図1は、典型的なマイクロチップデバイス10を示す。このマイクロチップデバイス10は、基板12と、リザーバ16と、リザーバキャップ14とを備える。このマイクロチップデバイスは、分子のキャリア流体中への能動的放出および受動的放出を提供する装置と一体化されている。この装置はある量のキャリア流体を含み得る。または、キャリア流体を装置の外部に設けても良い。
マイクロチップデバイスは典型的には、複数のリザーバを有する基板を含む。これらのリザーバは、放出される分子を含む放出システムを備える。いくつかの実施形態において、マイクロチップデバイスは、リザーバの開口部を被覆する1つ以上のリザーバキャップをさらに含む。これらのリザーバキャップの設計および形成に用いることが可能な材料としては、分子に対して選択的に透過性の材料、崩壊して分子を放出させる材料、破裂して分子を放出させる材料、またはこれらの組み合わせがある。能動的放出システムは、制御回路構成および電源をさらに含み得る。
基板は、エッチングされたリザーバ、成形されたリザーバまたは機械加工されたリザーバを含み、マイクロチップの支持部として機能する。基板として用いることが可能な材料としては、支持部として機能することができ、エッチング、成形または機械加工に適し、送達対象分子および周囲の流体(例えば、水、有機溶媒、血液、電解質または他の溶液)に対して不浸透性である材料であればよい。基板材料の例を挙げると、セラミック、半導体および分解性ポリマーおよび非分解性ポリマーがある。薬物を身体外部に送達する場合(例えば、吸入器中のガス状ストリームに薬物を放出する場合)、基板そのものに毒性が無いことが好ましいが、これは必須条件ではない。インビボ用途(例えば、ステントによる脈管流体中への薬物送達)の場合、殺菌済みの生体適合性材料を用いるのが好ましい。そうはいっても、用いる前に、毒性材料または別の場合において生体非適合性の材料を生体適合性材料(例えば、ポリ(エチレングリコール)またはテトラフルオロエチレンなどの材料)に封入してもよい。
送達される分子は、その純粋な形態で、液体の溶液またはゲルとして、リザーバに挿入され得るか、あるいはこれらは、放出システムの内部にかまたは放出システムによって、カプセル化され得る。本明細書中において使用される場合に、「放出システム」とは、固体もしくは液体として、分子が純粋な形態であるか、あるいは分解性材料、またはマトリックスからの拡散もしくはマトリックスの崩壊によって組み込まれた分子を放出する材料で形成されるマトリックス中にあるかの、両方の状況を包含する。分子は、時々、放出システムに収容され得る。なぜなら、放出システムの分解、溶解、または拡散の特性が、分子の放出速度を制御するための方法を提供するからである。分子は、放出システムに、相同にかまたは異種に分配され得る。放出システムの選択は、分子の放出の所望の速度に依存する。非分解性放出システムと分解性放出システムとの両方が、分子の送達のために使用され得る。適切な放出システムとしては、ポリマーおよびポリマーマトリックス、非ポリマーマトリックス、または無機物および有機物の賦形剤および希釈剤(例えば、炭酸カルシウムおよび糖であるが、これらに限定されない)を含む。放出システムは、天然物であっても合成物であってもよいが、合成放出システムは、放出プロフィールのより良好な特徴付けに起因して、代表的に好ましい。
((i)崩壊または拡散による受動的放出)
受動的タイミングを利用した放出薬物送達デバイスにおいて、リザーバキャップを形成する材料は、経時的に分解もしくは溶解するかまたは分解も溶解もせず、かつ、送達対象分子に対して浸透性である材料である。これらの材料は好適にはポリマー材料である。リザーバキャップ用途として選択することが可能な材料としては、分子の放出を異なるリザーバから異なるタイミングで(時には)異なる速度で行うことを可能にするような、様々な分解速度、溶解速度または浸透性が得られる材料がある。異なる放出タイミング(放出タイミングを遅らせる時間の長さ)を得るために、キャップは、異なるポリマー、架橋度が異なる同じポリマーまたはUVによって重合可能なポリマーから形成され得る。後者の場合、このポリマーをUV光に露出させる時間を変えると、架橋度が変わり、キャップ材料の拡散特性または分解速度もしくは溶解速度も異なってくる。異なる放出タイミングを得るための別の方法として、1種類のポリマーを用いて、そのポリマーの厚さを変更する方法がある。いくつかのポリマーの肉厚の膜を用いると、放出タイミングは遅延する。ポリマー、架橋度またはポリマー厚さの任意の組み合わせを変更して、特定の放出タイミングまたは速度を得ることが可能である。一実施形態において、送達対象分子を含む放出システムを、分子に対してほぼ不浸透性である分解性キャップ材料で被覆する。リザーバから分子を放出するタイミングは、キャップ材料の分解所要時間または溶解所要時間によって限定される。別の実施形態において、キャップ材料は非分解性であり、送達対象分子に対して浸透性である。使用される材料の物理的特性、その架橋度およびその厚さによって、キャップ材料を通じて分子が拡散するために必要な時間が決定する。放射対象分子の放出システムからの拡散に制約がある場合、そのキャップ材料は、放出の開始を遅延させる。放射対象分子のキャップ材料を通過する拡散に制約がある場合、そのキャップ材料は、分子の放出速度および放出開始の遅延を決定する。
能動的タイミングを利用した放出デバイスの一実施形態において、リザーバキャップは、導電性材料の薄膜からなる。この導電性薄膜は、リザーバ上に堆積され、所望のジオメトリにパターニングされ、アノードとして機能する。カソードも、デバイス上に作製される。これらのカソードのサイズおよび配置は、デバイスの用途および電位制御方法に依存する。アノードは、酸化を起こさせる電極として定義される。アノードおよびカソードを作製する際に用いることが可能な材料としては、電流または電位を受けると溶液に溶解するかまたは可溶性イオンもしくは酸化化合物を形成することができる(電気化学的溶解が可能な)導電性材料であれば任意の材料でよい。加えて、例えば、アノード近隣の局所のpHが変化することによって不溶性イオンまたは酸化生成物が可溶性になる場合、これらの酸化生成物を電位に応答して通常生成する材料を用いてもよい。リザーバキャップ材料として適切な材料を挙げると、金属(例えば、銅、金、銀、および亜鉛)、ならびに以下の文献に記載のいくつかのポリマーがある(例えば、Kwonらによる「Electrically erodible polymer gel for controlled release of drug」、Nature、354:291〜93(1991);およびBaeらによる「Pulsatile drug release by electric stimulus」、ACS Symposium Series、545:98〜110(1994)に記載の材料)。
別の実施形態において、リザーバキャップは、分子を覆ってリザーバ上に配置される。デバイスまたはその一部が加熱または冷却されると、分子はリザーバから放出され、これにより、リザーバキャップが破裂する。本明細書において用いられるように、「破裂」という用語は、破断または何らかの他の形態の機械的破損と、温度変化に応答して発生する相変化(例えば、溶解)に起因する構造的完全性の損失とを指す(ただし、これらの機構のうち特定の機構について言及される場合は除く)。
天然物または合成物、有機物または無機物の、任意の分子またはその混合物が、送達され得る。1つの実施形態において、静脈内送達される流体に薬物を放出することによって、薬物を患者に全身的に送達するために、マイクロチップが使用される。本明細書中において使用される場合に、用語「薬物」とは、他に示さない限り、治療剤、予防薬、および診断薬を包含する。静脈内薬物送達適用の間に放出される薬物分子としては、抗生物質、化学療法剤、インビボ診断薬(例えば、造影剤)、糖類、ビタミン、毒素抗体、抗炎症薬、鎮痛剤(pain killer)、および透析のような腎臓手順のために有用な薬剤(例えば、ヘパリン)が挙げられるが、これらに限定されない。別の実施形態において、マイクロチップは、治療的または審美的な目的のために、流体流に分子を放出する。例えば、液体または気体の流体の放出される分子としては、アロマテラピーヒドロゾル、種々の芳香性物質、着色剤、ならびに人工甘味料および天然甘味料が挙げられるが、これらに限定されない。分析化学の分野は、少量(ミリグラム〜ナノグラム)の1つ以上の分子が必要とされる、なお別の実施形態を提示する。効果的な例示の分子は、pH緩衝剤、診断剤、および複合体反応(例えば、ポリメラーゼ連鎖反応および他の核酸増幅手順)における試薬である。
キャリア流体中に分子を放出するための送達システムまたは装置は、さらに、特定の用途に依存して、種々の他の構成要素を備え得る。
いくつかの用途(例えば、以下に説明する静脈内の(IV)薬物管理システムの用途)に関する好適な実施形態において、本システムは、キャリア流体および放出対象薬物を組み合わせる場所である混合チャンバをさらに含む。本明細書において用いられるように、他に明記無き限り、「混合チャンバ」という用語は、マイクロチップデバイスからの分子がキャリア流体と接触することが可能である間にキャリア流体を一時的に保管することが可能な(例えば、キャリア流体を通過させることが可能な)任意の構造を指し得る。混合チャンバは、マイクロチップデバイス近隣に配置してもよいし、または、(キャリア流体が分子の放出元であるマイクロチップデバイスの表面を流れて通過する場所である)システムの下流の近隣に配置してもよい。キャリア流体および薬物は、濃度勾配または流体の化学的電位の低下に起因する拡散によって局所的に混合する。
一実施形態において、マイクロチップデバイスはステントに一体化される。現在、ステントは、広範囲の医療用に用いられており、通常は血管の再閉鎖を防止するために用いられている。ステントの例を挙げると、心臓血管用途のステントおよび胃腸用途のステントがある。これらのステントは通常は非分解性である。尿管用ステントおよび尿道用ステントは、様々な良性条件、悪性条件および外傷後条件における閉鎖(例えば、石の存在および/もしくは小石の存在、または他の尿管の閉鎖(例えば、尿管狭窄、腹部臓器の腫瘍、腹膜後の繊維症もしくは尿管外傷に関連する尿管障害、または、体外衝撃波療法に関連する尿管閉鎖)を軽減するために用いられる。ステントは、内視鏡を用いた外科技術を用いてかまたは経皮的に配置することができる。最先端のステントの例を挙げると、ダブルピグテール(double pigtail)尿管ステント(C.R.Bard,Inc.,Covington,GA)、SpiraStent(Urosurge,Coralville,IA)、およびCook泌尿器用ステント、尿管用ステントおよび尿道用ステント(Cook Urological,Spencer,IN)がある。
マイクロチップデバイスのリザーバに収容される分子は、特定の用途に依存して、種々のキャリア流体に送達され得る。キャリア流体は、本質的に、流体形態の任意の組成物であり得る。本明細書中において使用される場合に、用語「流体」とは、液体、気体、超臨界流体、溶液、懸濁液、ゲル、およびペーストを包含するが、これらに限定されない。
1つの好適な実施形態は、電気化学的刺激に応答して分子を放出するマイクロチップからの液状キャリアへの分子の能動的放出である。この様子を図3に示す。電位(図3aを参照)が与えられると、キャップ材料は溶解(図3bを参照)し、その結果、図3cに示すように、分子は、リザーバ開口部近隣を流れる液体中に放出される。好適な実施形態において、電流は、変調され、一定の値では維持されない。
Devices and Systems」(Proceedings−IEEE Micro Electro Mechanical Systems、114〜19ページ(1991))およびゾル−ゲル処理(例えば、Kleinによる「Sol−Gel Optics:Processing and Applications」(Kluwer Academic Publishers、1994)に記載のゾル−ゲル処理))。超音波エネルギーの供給は、送達デバイス上に配置された構成要素、キャリア流体中に配置された構成要素または送達デバイスの外部に配置された構成要素によって行うことが可能である。露出させるリザーバを選択する方法としては、例えば、第2の超音波を用いた波干渉がある。これらの第2の波は、第1の超音波と干渉して破壊する機能を行うことができ、これにより、エネルギー付加を選択された一連のリザーバのみに限定する。
マイクロチップデバイスは、例えば、当該分野において公知の技術(特にSantiniらに付与された米国特許第6,123,861号に記載の方。同特許を参考のため援用する)を用いて作製可能である。同特許に記載の作製方法では微細加工技術および微細電子処理技術が用いられているが、能動的マイクロチップによる化学的送達デバイスおよび受動的マイクロチップによる化学的送達デバイスの作製は、半導体などの材料または微細電子機器製造において典型的に用いられるプロセスに限定されないことが理解される。例えば、他の材料(例えば、金属、セラミックおよびポリマー)をデバイス中において用いることが可能である。同様に、他の作製プロセス(例えば、めっき、キャスティングまたは成形)を用いてデバイスを作製してもよい。
マイクロチップ送達システムを用いて、様々な形態の様々なキャリア流体中に分子を放出させることが可能である。分子放出の代表例を挙げると、患者(例えば、静脈系または呼吸系)に導入または投与するべき流体中への薬物送達;移植されたシステム(例えば、ステントまたは微細ポンプ)からの薬物送達;分析化学もしくは診断化学;芳香物放出システム;および飲料添加剤システムがある。
1つ以上のマイクロチップ化学物質送達デバイスを備える、静脈内(IV)薬物送達システムが、提供される。このデバイスは、静脈内投与のための生理学的に受容可能なキャリア流体中に、分子を放出する。
キャリア流体中への分子の放出のためのマイクロチップデバイスの1つの実施形態は、1つ以上の薬物送達マイクロチップを、ステント(例えば、脈管ステント)の内部/表面に組み込むことを包含する。薬物収容マイクロチップは、好ましくは、このステントの1つ以上の表面に提供される(例えば、図9a〜cに示すように)。マイクロチップデバイスは、移植およびステント拡張の間に、ステント内に存在し得るか、またはマイクロチップデバイスは、ステントの移植および拡張の直後に、別の手順においてステントの内部に取り付けられ得る。マイクロチップが十分に小さい場合には、マイクロチップのステントへの移植および取り付けは、ステントの移植において使用したものと同じカテーテル送達技術を使用して、完了され得る。好ましい実施形態において、ステント−マイクロチップデバイスのマイクロチップは、遠隔手段または無線手段によって、そのステントから薬物を直接送達するように、プログラムまたは作動される。
別の実施形態において、マイクロチップデバイスは、患者による引き続く吸入のための気体状キャリア流体(例えば、空気)に分子を放出するために使用される。1つのシステムにおいて、例えば、薬物を収容しているマイクロチップデバイスは、計量された用量の吸入器(MDI)に組み込まれて、送達される分子の用量を正確に制御するための簡単な方法を提供する。マイクロチップデバイスはまた、制御された環境(リザーバ内)を提供し、これは、貯蔵された薬物の安定性を延長するよう機能し得る。
別の実施形態において、気体状のキャリア流体(代表的には、空気)内への芳香性分子の送達のためのシステムが提供される。これらのシステムは、芳香性物質を収容するマイクロチップデバイスを備え、このデバイスは、1つ以上の芳香性物質の送達のための種々の装置に組み込まれ得る。芳香性分子は、例えば、芳香剤、アロマテラピー剤、室内の脱臭または臭気マスキングのための化学物質、ならびに任意の目的で香気および芳香の送達を発生または刺激するための分子であり得る。芳香性分子は、図4〜6において先に記載した方法を使用して、周囲の環境に放出され得る。
さらなる実施形態において、1つ以上の添加剤をキャリアに送達して、1つ以上の消費者用飲料を形成するためのシステムが、提供される。添加剤分子を収容するマイクロチップデバイスは、この添加剤分子を、液体のキャリア流体(これは、代表的に、1つ以上の添加剤のみを欠く飲料であるか、または最終的に飲料が形成される水もしくは別のベースである)に選択的に放出する。代表的な添加剤としては、天然または人工の香味剤、甘味料、調味料、および着色料が挙げられる。分子の放出は、能動的または受動的であり得る。
液体および気体状のキャリア流体中に放出するための分子を収容するマイクロチップは、診断および分析化学において、広範な潜在的な用途を有する。診断システムの1つの実施形態において、本明細書中に記載されるマイクロチップ技術は、DNA試験、血液分析、または環境サンプルの試験において使用される微小流体アレイに統合され得る。好ましい実施形態において、生理食塩水溶液のようなキャリア流体が、微小流体アレイにおける極小のチャネルを通して電気泳動的にポンピングされる。試薬分子を収容し、そして能動リザーバキャップを有するリザーバが、微小流体チャネルの底部に沿って配置される。生理食塩水溶液が、試薬で満たされたリザーバをを収容するチャネル内にポンピングされるにつれて、信号(例えば、電流)がリザーバキャップに送られて、これらの分解を引き起こし、リザーバの内部の試薬をチャネル内の生理食塩水溶液中に拡散させる。試薬の放出は、流体がリザーバの上で止まっている間か、またはキャリア流体がリザーバのそばを流れれている間に起こり得る。試薬を含有する生理食塩水溶液が、ここで混合チャンバにポンピングされ、このチャンバで、試薬が目的のサンプル(例えば、血液サンプル)と混合されて、所望の相互作用が起こる。
別の実施形態において、マイクロチップデバイスは、例えば延長した期間にわたる薬物の送達(糖尿病患者へのインスリンの送達および特定の種類の重篤な慢性的疼痛の処置が必要である場合など)のために、移植可能な微小ポンピングシステムに組み込まれる。これらのデバイスにおいて使用するために適切なマイクロポンプ装置は、当該分野において公知である(例えば、Rosenbergに対する米国特許第4,596,575号を参照のこと)。マイクロポンプは、キャリア流体を、マイクロチップデバイスの1つ以上の表面を横切ってポンピングする。種々のキャリア流体が、ポンピングされる流体として作用し得、濾過された細胞外流体、生理食塩水溶液、または水が挙げられるが、これらに限定されない。
腎臓透析手順において、患者の血液は、エキソビボで、透析器を通って流れ、ここで、毒性の分子が選択的に血液から除去され、そして「洗浄された」血液が、患者の身体に戻される。これらの毒性分子(これらは通常、腎臓によって血液から除去される)は、腎臓の減少した機能または受適切な機能に起因して、経時的に蓄積する。毒性分子は、血液が透析器を通過するにつれて患者の血液から除去され、同時に治療分子および薬物が、血液に容易に添加され得る。これは、複数の薬物または他の分子を、エキソビボに配置されたマイクロチップデバイスを使用して、患者に全身送達するための、潜在的な方法を導く。好ましい実施形態において、薬物分子で満たされたマイクロチップデバイスは、透析手順の間に血液が流れるチュービング内に配置される。マイクロチップは、血液がこのチュービングを通過するにつれて、患者の血液に1つ以上の型の分子を、能動的にかまたは受動的に送達し得る。この方法は、送達デバイスを患者の身体に移植する必要なく、複数の薬物が正確かつ直接的に患者の血液中に送達されることを可能にする。
Claims (1)
- キャリア流体内への分子の制御放出のための装置であって、以下:
(i)放出のための該分子を収容する複数のリザーバを有する、マイクロチップデバイス、および
(ii)キャリア流体が流れ得る構造を備える混合チャンバであって、該混合チャンバは、該キャリア流体の流れに関して、該マイクロチップデバイスに隣接するかまたは該マイクロチップデバイスの下流に位置する、混合チャンバ、
を備え、ここで、該分子が、該リザーバの1つ以上からの該分子の放出に続いて、該キャリア流体と混合される、装置。
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2000
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- 2000-11-17 AT AT00978732T patent/ATE425738T1/de not_active IP Right Cessation
- 2000-11-17 ES ES00978732T patent/ES2332869T3/es not_active Expired - Lifetime
- 2000-11-17 EP EP00978732A patent/EP1229901B1/en not_active Expired - Lifetime
- 2000-11-17 EP EP06075443.9A patent/EP1690527B1/en not_active Expired - Lifetime
- 2000-11-17 US US09/715,493 patent/US6491666B1/en not_active Expired - Lifetime
- 2000-11-17 AU AU16162/01A patent/AU770395B2/en not_active Ceased
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- 2006-08-14 JP JP2006220882A patent/JP2006328083A/ja not_active Withdrawn
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2009
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2011
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20150122288A (ko) * | 2014-04-22 | 2015-11-02 | 한국과학기술원 | 플렉서블 약물 전달 소자 제조방법 및 플렉서블 약물 전달 소자 |
KR101967133B1 (ko) | 2014-04-22 | 2019-04-10 | 한국과학기술원 | 플렉서블 약물 전달 소자 제조방법 및 플렉서블 약물 전달 소자 |
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US20110245914A1 (en) | 2011-10-06 |
US20030100865A1 (en) | 2003-05-29 |
JP2003513755A (ja) | 2003-04-15 |
EP2308522A2 (en) | 2011-04-13 |
US20040260391A1 (en) | 2004-12-23 |
CA2392006A1 (en) | 2001-05-25 |
ES2332869T3 (es) | 2010-02-15 |
EP1229901B1 (en) | 2009-03-18 |
US6491666B1 (en) | 2002-12-10 |
US6656162B2 (en) | 2003-12-02 |
EP1690527B1 (en) | 2015-01-07 |
JP2009261961A (ja) | 2009-11-12 |
US7052488B2 (en) | 2006-05-30 |
EP1229901A1 (en) | 2002-08-14 |
CA2392006C (en) | 2011-03-15 |
EP1690527A3 (en) | 2009-08-05 |
US20060217798A1 (en) | 2006-09-28 |
US6537256B2 (en) | 2003-03-25 |
EP1690527A2 (en) | 2006-08-16 |
AU770395B2 (en) | 2004-02-19 |
ATE425738T1 (de) | 2009-04-15 |
US7041130B2 (en) | 2006-05-09 |
AU1616201A (en) | 2001-05-30 |
US20020173745A1 (en) | 2002-11-21 |
US20040034332A1 (en) | 2004-02-19 |
EP2308522A3 (en) | 2012-02-29 |
WO2001035928A1 (en) | 2001-05-25 |
JP2012071142A (ja) | 2012-04-12 |
DE60041825D1 (de) | 2009-04-30 |
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