JP2009506074A - 自己アセンブルされる血管内構造物 - Google Patents
自己アセンブルされる血管内構造物 Download PDFInfo
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Abstract
Description
本発明の多数の態様と実施形態の以下の詳細な説明を参照することによって本発明のさらに完全な理解が得られる。以下の実施形態の詳細な説明は、本発明を説明することを意図するものであり、決して限定するものではない。
本発明による組成物は、様々な経路を介して注入することができ、かかる経路には、とりわけ、血管内注入(例えば、静脈内注入、動脈内注入、冠動脈内注入、心臓内注入など)、筋肉内注入、皮下注入、および腹腔内注入経路が含まれる。注入はシリンジ、静脈薬物送達カテーテル、動脈薬物送達カテーテルなどを含む様々な公知の医療デバイスを介して実施することができる。ある特定の実施形態においては、薬物送達カテーテルは、薬物送達をより局在化し、全身送達を少なくすることを容易にするので有利である。様々な薬物送達カテーテル設計が公知であり、それらには、とりわけ、灌流カテーテル、注入カテーテル、および二重バルーンカテーテルが含まれる。
他の実施形態においては、粒子間結合リガンドの1つまたは両方はヒドロゲルポリマー内に包埋される。ヒドロゲルポリマーを疎水性から親水性の状態に移行させる(この事象はまたヒドロゲルの膨潤も伴う)かまたはヒドロゲルポリマーを親水性から疎水性の状態に移行させる誘発事象が起こると、結合リガンドはヒドロゲルから生体環境中に放逐/放出されうる。例えば、ヒドロゲルはpH、浸透圧濃度または温度の変化で、電場の適用時になどに基づいてより親水性になることが知られている。例えば、Chatterjeeら, Nanotech 2003 Vol. 1, Technical Proceedings of the 2003 Nanotechnology Conference and Trade Show, Volume 1, Chapter 7: Bio Micro Systems, 「電気的に誘発されるヒドロゲル:数学モデルとシミュレーション(Electrically Triggered Hydrogels: Mathematical Models and Simulations)」” pp. 130 - 133;Eichenbaum GMら, 「pHとイオンで誘発される陰イオン性ヒドロゲル微小球の体積応答(pH and Ion-Triggered Volume Response of Anionic Hydrogel Microspheres)」, Macromolecules. 1998 Jul 28;31(15):5084-93;Chen ら, 「titin 免疫グロブリンモジュールにより調節される体積遷移を伴う応答性ハイブリッドヒドロゲル(Responsive hybrid hydrogels with volume transitions modulated by a titin immunoglobulin module)」 Bioconj. Chem. 2000 Sep-Oct;11(5): 734-40;Coughlan DCら, 「熱応答性ポリ(N-イソプロピルアクリルアミド)ヒドロゲルの膨潤/脱膨潤動力学および拍動性薬物放出に与える薬物物理化学的特性の効果(Effect of drug physicochemical properties on swelling/deswelling kinetics and pulsatile drug release from thermoresponsive poly(N-isopropylacrylamide) hydrogels)」, J Control Release. 2004 Jul 23;98(1):97-114;Molinaro Gら, 「感熱性キトサン系ヒドロゲルの生体適合性:注入可能な生体材料のin vivo実験研究(Biocompatibility of thermosensitive chitosan-based hydrogels: an in vivo experimental approach to injectable biomaterials)」 Biomaterials. 2002 Jul;23(13):2717-22;Wang Cら, 「遺伝子操作で作られたコイルドコイルブロックタンパク質により架橋されたハイブリッドヒドロゲル(Hybrid hydrogels cross-linked by genetically engineered coiled-coil block proteins)」 Biomacromolecules. 2001 Fall;2(3):912-20を参照されたい。従って、上記ヒドロゲルポリマーならびに他の現在利用しうるポリマーマトリックスを用いて、例えば、ポリマー中のイオン基をイオン化する局所的pH変化により(例えば、その領域をカテーテルを介し酸性または塩基性溶液を用いて洗浄することにより)、加熱して(例えば、MRIにより加熱するかまたはその領域をカテーテルを介し温溶液で洗浄することにより)水和を可能にする臨界的遷移を超えるポリマーの変換を強いることにより、または加水分解/酵素切断をしてポリマー中の親水基を曝すことにより、リガンド放出を誘発することができる。リガンド被覆と暴露だけでなく(またはその代わりに)、かかる誘発可能なヒドロゲルを利用して薬物を保持しかつ放出することができる。
磁場を適用するとサイズが変化する磁気歪み(磁歪)粒子も公知である。
M-OH + SiCl4 → M-O-SiCl3 + HCl
[式中、Mは金属またはセラミック表面に対応する]。これらが表面上に作製されると、次いでクロロシラン基をそれと反応する分子(例えば、ヒドロキシル基を含む化学種)に曝し、それにより共有結合した分子化学種を形成させる。
Claims (28)
- 自己アセンブル性ナノ粒子を含んでなる注入可能な組成物であって、前記自己アセンブル性ナノ粒子が(a)ナノ粒子部分、(b)組成物を身体中に注入すると、1以上の標的化した組織位置でナノ粒子の優先的な結合および蓄積を生じるナノ粒子部分に付着した組織結合リガンド、および(c)1以上の標的化した組織位置で粒子間結合を生じる、ナノ粒子に付着した第1および第2粒子間結合リガンドを含む、前記組成物。
- 第1および第2粒子間結合リガンドの少なくとも1つが1以上の標的化した組織位置においてin vivoで活性化される、請求項1に記載の組成物。
- ナノ粒子部分が球状ナノ粒子部分、平面形状ナノ粒子部分、および伸長したナノ粒子部分から選択される、請求項1に記載の組成物。
- ナノ粒子部分が無機ナノ粒子部分である、請求項1に記載の組成物。
- 無機ナノ粒子部分が金属性ナノ粒子部分である、請求項4に記載の組成物。
- ナノ粒子部分が有機ナノ粒子部分である、請求項1に記載の組成物。
- 有機ナノ粒子部分がポリマーナノ粒子部分である、請求項6に記載の組成物。
- 誘発処置を行うことによりナノ粒子部分の形状をin vivoで変えることができる、請求項1に記載の組成物。
- ナノ粒子部分が形状記憶を有する、請求項8に記載の組成物。
- ナノ粒子部分が形状記憶金属または形状記憶ポリマーから形成される、請求項9に記載の組成物。
- 形状記憶を誘発するとナノ粒子部分が拡大する、請求項9に記載の組成物。
- 形状記憶を誘発するとナノ粒子部分が収縮する、請求項9に記載の組成物。
- ナノ粒子部分が熱収縮性材料から形成される、請求項8に記載の組成物。
- 自己アセンブル性ナノ粒子が放出しうる接着化学種を含む、請求項1に記載の組成物。
- 自己アセンブル性ナノ粒子がin vivoでかつナノ粒子自己アセンブリーの後に放出される薬物を含む、請求項1に記載の組成物。
- 薬物がナノ粒子部分と共有結合している、請求項15に記載の組成物。
- 薬物が封入されかつナノ粒子部分に付着している、請求項15に記載の組成物。
- ナノ粒子部分が薬物を含む、請求項15に記載の組成物。
- ナノ粒子部分が封入された薬物を含む、請求項15に記載の組成物。
- 薬物が抗再狭窄薬、抗血栓薬、増殖因子、抗炎症薬、細胞接着タンパク質、およびそれらの組合わせから選択される、請求項15に記載の組成物。
- 自己アセンブル性ナノ粒子が磁性ナノ粒子を含む、請求項1に記載の組成物。
- 組織結合リガンドが抗体、インテグリン、細胞レセプター模倣物およびそれらの組合わせから選択される、請求項1に記載の組成物。
- 第1および第2粒子間結合リガンドが抗体-抗原対を含む、請求項1に記載の組成物。
- ナノ粒子のin vivo自己アセンブリーのためのキットであって、
(a)(i)第1のナノ粒子部分、(ii)第1の組成物を身体中に注入すると、1以上の標的化した組織位置で第1の自己アセンブル性ナノ粒子の優先的な結合および蓄積を生じる第1のナノ粒子部分に付着した組織結合リガンド、および(iii)粒子間結合を促進する第1のナノ粒子部分に付着した第1の粒子間結合リガンド、を含む第1の自己アセンブル性ナノ粒子を含んでなる第1の注入可能な組成物;ならびに
(b)(i)第2のナノ粒子部分、および(ii)第2の組成物を身体中に注入すると、第1のナノ粒子の第1の粒子間結合リガンドと優先的に結合する第2のナノ粒子部分に付着した第2の粒子間結合リガンド、を含む第2の自己アセンブル性ナノ粒子を含んでなる第2の注入可能な組成物を含んでなり、
前記第1および第2のナノ粒子部分は同じまたは異なる材料から形成されてもよい前記キット。 - 第2の自己アセンブル性ナノ粒子がさらに、身体中に注入すると、1以上の標的位置で第2のナノ粒子の組織との優先的結合を生じる第2の粒子部分に付着した組織結合リガンドを含む、請求項24に記載のキット。
- 第2の自己アセンブル性ナノ粒子がさらに第2のナノ粒子部分に付着した組織結合リガンドを含まない、請求項24に記載のキット。
- さらに、(i)第3のナノ粒子部分および(ii)身体中に注入すると第2のナノ粒子の第2の粒子間結合リガンドと優先的に結合する第3のナノ粒子部分に付着した第3の粒子間結合リガンドを含む第3の自己アセンブル性ナノ粒子を、含んでなる第3の注入可能な構成成分を含んでなり、前記第3の自己アセンブル性ナノ粒子はさらに第3のナノ粒子部分に付着した組織結合リガンドを含まず、第1、第2および第3のナノ粒子部分は同じもしくは異なる材料から形成されてもよく、そして、前記第1および第3の粒子間結合リガンドは同じかもしくは異なってもよい、請求項24に記載のキット。
- 有機ナノ粒子部分がタンパク質を含む、請求項6に記載の組成物。
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US11/211,809 US20070048383A1 (en) | 2005-08-25 | 2005-08-25 | Self-assembled endovascular structures |
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Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20121113 |