JP2022177012A - 生物医学的応用のための制御可能な自己アニーリング型ミクロゲル粒子 - Google Patents
生物医学的応用のための制御可能な自己アニーリング型ミクロゲル粒子 Download PDFInfo
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Abstract
Description
本出願は、2014年7月17日に出願された米国仮特許出願第62/025,844号、2014年10月3日に出願された同第62/059,463号、および2015年1月13日に出願された同第62/103,002号に基づく優先権を主張する。米国特許法第119条によって優先権が主張される。上記特許出願は本明細書に完全に記載されたかの如く参照により援用される。
Claims (66)
- 複数のミクロゲル粒子を含む水溶液;および
複数のミクロゲル粒子に適用された場合に、ミクロゲル粒子に、内部間隙を有する共有結合的に安定化したミクロゲル粒子から成る足場を形成させるアニーリング剤、
を含む、微小孔性ゲル系。 - ミクロゲル粒子が分解性架橋剤をさらに含む、請求項1に記載の微小孔性ゲル系。
- 分解性架橋剤がマトリクスメタロプロテアーゼ(MMP)-分解性架橋剤を含む、請求項2に記載の微小孔性ゲル系。
- アニーリング剤が活性化第XIIIa因子を含む、請求項1に記載の微小孔性ゲル系。
- アニーリング剤がエオシンY、フリーラジカル移動剤、またはこれらの組合せを含む、請求項1に記載の微小孔性ゲル系。
- 複数のミクロゲル粒子およびアニーリング剤の混合物を照射するように構成された光源をさらに含む、請求項5に記載の微小孔性ゲル系。
- ミクロゲル粒子がその表面上に露出される細胞接着性ペプチドを含む、請求項1に記載の微小孔性ゲル系。
- ミクロゲル粒子がK-ペプチドを含む、請求項1に記載の微小孔性ゲル系。
- K-ペプチドが活性化第XIIIa因子によって認識されるリジン基を含む、請求項8に記載の微小孔性ゲル系。
- ミクロゲル粒子がQ-ペプチドを含む、請求項1に記載の微小孔性ゲル系。
- Q-ペプチドが活性化第XIIIa因子によって認識されるグルタミン基を含む、請求項10に記載の微小孔性ゲル系。
- 間隙が負の凹面を示す境界面を含む、請求項1に記載の微小孔性ゲル系。
- ミクロゲル粒子の共有結合的に安定化した足場が約10%~約50%の空隙容量を有する、請求項1に記載の微小孔性ゲル系。
- 送達デバイスをさらに含む、請求項1に記載の微小孔性ゲル系。
- 送達デバイスが複数のミクロゲル粒子を含む水溶液およびアニーリング剤またはアニーリング剤前駆物質を含有する、請求項14に記載の微小孔性ゲル系。
- 送達デバイスが複数のミクロゲル粒子を含む水溶液およびアニーリング剤を含有する単一区画送達デバイスを含む、請求項15に記載の微小孔性ゲル系。
- 送達デバイスが二重区画送達デバイスを含み、一方の区画が複数のミクロゲル粒子を含有する水溶液および第一アニーリング剤前駆物質を含有し、第二の区画が複数のミクロゲル粒子を含有する水溶液および第二アニーリング剤前駆物質を含有する、請求項16に記載の微小孔性ゲル系。
- (MMP)-分解性架橋剤が少なくとも1つのD-アミノ酸を含む、請求項3に記載の微小孔性ゲル系。
- ミクロゲル粒子が複数のD-アミノ酸を含む(MMP)-分解性架橋剤を含む、請求項18に記載の微小孔性ゲル系。
- 送達デバイス;
水溶液中に含有され、送達デバイス内に貯蔵される、複数の生分解性ミクロゲル粒子;および
送達デバイス内に貯蔵されるアニーリング剤またはアニーリング剤前駆物質、
を含む、微小孔性ゲル系。 - 水溶液中に含有され、送達デバイス内に貯蔵される、2種以上の生分解性ミクロゲル粒子の集合をさらに含む、請求項20に記載の微小孔性ゲル系。
- 送達デバイスが2つの区画を含み、生分解性ミクロゲル粒子が2つの区画のそれぞれに貯蔵され、第一アニーリング前駆物質が一方の区画内に貯蔵され、第二アニーリング前駆物質が他方の区画内に貯蔵され、アニーリング剤が第一アニーリング前駆物質および第二アニーリング前駆物質の両方の存在によって形成される、請求項20に記載の微小孔性ゲル系。
- 送達デバイスが単一区画を含み、生分解性ミクロゲル粒子の集合およびアニーリング剤が共に単一区画内に貯蔵される、請求項21に記載の微小孔性ゲル系。
- アニーリング剤が単一区画内に貯蔵される光開始剤およびフリーラジカル移動剤を含む、請求項23に記載の微小孔性ゲル系。
- 生分解性ミクロゲル粒子の集合およびアニーリング剤の混合物を照射するように構成された発光デバイスをさらに含む、請求項24に記載の微小孔性ゲル系。
- 生分解性ミクロゲル粒子が実質的に単分散の球体を含む、請求項20に記載の微小孔性ゲル系。
- 実質的に単分散の球体が約30マイクロメーター~約150マイクロメーターの範囲内の直径を有する、請求項26に記載の微小孔性ゲル系。
- 生分解性ミクロゲル粒子がアニーリング後に互いに共有結合的に連結される、請求項21に記載の微小孔性ゲル系。
- 組織を治療する方法であって、
複数のミクロゲル粒子を含有する水性溶液を組織に送達し;
複数のミクロゲル粒子を、ミクロゲル粒子をアニールすることで内部間隙を有する共有結合的に安定化したミクロゲル粒子から成る足場を形成させるアニーリング剤に暴露すること、
を含む、前記方法。 - 複数のミクロゲル粒子が細胞接着性ペプチドで装飾されており、ミクロゲル粒子がマトリクスメタロプロテアーゼ(MMP)-分解性架橋剤を用いて形成される、請求項29に記載の方法。
- アニーリング剤が組織に送達される、請求項29に記載の方法。
- アニーリング剤が組織内に存在する、請求項29に記載の方法。
- 露光によりミクロゲル粒子のアニーリングを開始させることをさらに含む、請求項29に記載の方法。
- 光の波長が赤外領域内である、請求項33に記載の方法。
- 光の波長が可視域内である、請求項33に記載の方法。
- 水性溶液およびアニーリング剤が同時に送達される、請求項29に記載の方法。
- 水性溶液およびアニーリング剤が順に送達される、請求項29に記載の方法。
- ミクロゲル粒子が治療効果のある化学物質を含む、請求項29に記載の方法。
- ミクロゲル粒子が前記化学物質を組織に露出または溶離する、請求項38に記載の方法。
- 組織が美容的再建、長期に亘る創傷発達、急性組織損傷、または外科的切開により生じた組織間隙の部位を含む、請求項29に記載の方法。
- (MMP)-分解性架橋剤が少なくとも1つのD-アミノ酸を含む、請求項30に記載の方法。
- 一つまたは複数の細胞接着部分、一つまたは複数のアニーリング成分、および一つまたは複数の生分解性ネットワーク架橋剤成分を有する骨格ポリマーを含むミクロゲル粒子の集合;並びに
アニーリング成分を介してミクロゲル粒子をインサイツで連結して、内部間隙を有する共有結合的に安定化したミクロゲル粒子から成る足場を形成させる、内在性または外来性のアニーリング剤、
を含む、微小孔性ゲル系。 - 骨格ポリマーがポリ(エチレングリコール)ビニルスルホンを含む、請求項42に記載の微小孔性ゲル系。
- 一つまたは複数の細胞接着部分がRGDペプチドもしくはその断片、フィブロネクチンもしくはその断片、コラーゲンもしくはその断片、またはラミニンもしくはその断片を含む、請求項42に記載の微小孔性ゲル系。
- 一つまたは複数の細胞接着部分が配列番号3またはその断片を含む、請求項42に記載の微小孔性ゲル系。
- 一つまたは複数のアニーリング成分がK-ペプチドおよびQ-ペプチドを含む、請求項42に記載の微小孔性ゲル系。
- K-ペプチドが活性化第XIIIa因子によって認識されるリジン基を含み、Q-ペプチドが活性化第XIIIa因子によって認識されるグルタミン基を含む、請求項46に記載の微小孔性ゲル系。
- 生分解性ネットワーク架橋剤成分がマトリクスメタロプロテアーゼ(MMP)-分解性架橋剤を含む、請求項42に記載の微小孔性ゲル系。
- (MMP)-分解性架橋剤が少なくとも1つのD-アミノ酸を含む、請求項48に記載の微小孔性ゲル系。
- ミクロゲル粒子の集合が2種以上のミクロゲル粒子を含む、請求項42に記載の微小孔性ゲル系。
- 第一の種類のミクロゲル粒子がD-アミノ酸を含む(MMP)-分解性架橋剤を含み、第二の種類のミクロゲル粒子がL-アミノ酸のみを含む(MMP)-分解性架橋剤を含む、請求項50に記載の微小孔性ゲル系。
- ミクロゲル粒子の集合およびアニーリング剤を含有する単一区画送達デバイスをさらに含む、請求項42に記載の微小孔性ゲル系。
- 二重区画送達デバイスをさらに含み、一方の区画が複数のミクロゲル粒子を含有する水溶液および第一アニーリング剤前駆物質を含有し、第二の区画が複数のミクロゲル粒子を含有する水溶液および第二アニーリング剤前駆物質を含有し、アニーリング剤が第一アニーリング剤前駆物質および第二アニーリング剤前駆物質の存在によって形成される、請求項42に記載の微小孔性ゲル系。
- 組織を治療する方法であって、
細胞接着性ペプチドで装飾されたミクロゲル粒子の第一層を組織に送達し、ここで、ミクロゲル粒子は生分解性架橋剤を用いて形成され;
ミクロゲル粒子をアニールすることで内部間隙を有する共有結合的に安定化したミクロゲル粒子から成る足場を形成させるアニーリング剤に第一層を暴露し;
細胞接着性ペプチドで装飾されたミクロゲル粒子の第二層を組織に送達し、ここで、ミクロゲル粒子は生分解性架橋剤を用いて形成され、第二層中のミクロゲル粒子は第一層中のミクロゲル粒子と比較して物性または化学組成の一方において異なり;
ミクロゲル粒子をアニールすることで内部間隙を有する共有結合的に安定化したミクロゲル粒子から成る足場を形成させるアニーリング剤に第二層を暴露すること、
を含む、前記方法。 - 第二層中のミクロゲル粒子が異なるサイズを有する、請求項54に記載の方法。
- 第二層中のミクロゲル粒子が異なる形状を有する、請求項54に記載の方法。
- 第二層中のミクロゲル粒子が異なる剛性を有する、請求項54に記載の方法。
- 第二層中のミクロゲル粒子が第一層における化学成分と異なる化学成分を有する、請求項54に記載の方法。
- 第二層中のミクロゲル粒子が第一層における同一の化学成分と異なる濃度の化学成分を有する、請求項54に記載の方法。
- 組織を治療する方法であって、
細胞接着性ペプチドで装飾された複数のミクロゲル粒子を含有する水性溶液を組織に送達し、ここで、ミクロゲル粒子は生分解性架橋剤を用いて形成され;
複数のミクロゲル粒子を、ミクロゲル粒子をアニールすることで内部間隙を有する共有結合的に安定化したミクロゲル粒子から成る足場を形成させるアニーリング剤に暴露すること、
を含む、前記方法。 - ミクロゲル粒子を作製する方法であって、
共通チャネルに通じる複数の投入チャネルおよび下流位置で共通チャネルと交差する油狭窄(oil-pinching)チャネル対を有する、油中水滴を発生させるマイクロ流体デバイスを準備し;
オリゴペプチドで修飾されたポリマー骨格を含有する第一プレポリマー溶液を第一投入チャネルに流し込み;
生分解性架橋剤を含有する第二溶液を第二投入チャネルに流し込み;
油および界面活性剤を油狭窄チャネル対に流し込むことで、第一プレポリマー溶液および第二溶液を含有する液滴を形成させ;
前記液滴の架橋結合によって形成されたミクロゲル粒子を収集すること、
を含む、前記方法。 - 第一投入チャネルと第二投入チャネルの間に挿入された第三投入チャネルを有し、プレポリマーを含有する第三の不活性溶液が第三投入チャネルに流し込まれる、請求項61に記載の方法。
- 発生した液滴を、油狭窄チャネル対が共通チャネルと交差する位置の下流に位置する追加の被覆用(sheathing)チャネル対で被覆することをさらに含み、追加の被覆用チャネル対が油および油狭窄チャネル対の上流で含有される界面活性剤よりも高い濃度の界面活性剤を保有する、請求項61に記載の方法。
- 収集されたミクロゲル粒子を遠心することをさらに含む、請求項62に記載の方法。
- 遠心されたミクロゲル粒子の自由水体積含量を減少させることをさらに含む、請求項63に記載の方法。
- 収集されたミクロゲル粒子を長期間貯蔵することをさらに含む、請求項64に記載の方法。
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