JP2009522001A - 歯の骨の欠損を治療するための光硬化性骨成長材料 - Google Patents
歯の骨の欠損を治療するための光硬化性骨成長材料 Download PDFInfo
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Abstract
Description
本願は、2005年12月28日に出願された米国特許仮出願第60/754,453号の利益を主張し、その全体内容を参照により本明細書中に援用する。
[実施例1]
概して、非特許文献2に記載の方法(以下、「Leach法」と称する)に従って、GMHyキャリアを調製した。
概して、非特許文献3に記載の方法に従って、Hy−MAキャリアを調製した。
概して、Leach法に従ってGAHyマクロマーを調製した。
GMHyキャリアの合成は成功した。約8%のGMHyを用いて作製したゲルは成功裏に光重合された。Hy−MAの合成は成功したが、Hy−MAを用いて作製した硬化ゲルは、Hy−MA濃度を低下させても、内部に混合した粒子の有無に関わらず、すべて非常に脆かった。また、反応混合物及び誘導体化材料は共に不透明であり、溶解性の問題を示唆した。GAHy合成は成功したが、材料の取扱いが非常に困難であった。水又は緩衝液への溶解性が低かった。GAHyを用いて作製した硬化ゲルは、内部に混合した粒子の有無に関わらず、非常に脆かった。
[実施例2]
[実施例3]
概して、Leach法に従ってGMHyキャリアを調製した。
概して、Leach法に従ってGMHyキャリアを調製した。
概して、Leach法によってGMHyキャリアを調製した。
概して、Leach法によってGMHyキャリアを調製した。
概して、Leach法に従ってGMHyキャリアを調製した。
[実施例4]
1% HECを室温で24時間、10倍モル過剰のグリシジルメタクリレート並びに等量のトリエチルアミン及びテトラブチルアンモニウムブロミドと水中で反応させた。反応を60℃で1時間継続した。反応後、溶液をアセトン中で沈殿させ、DI水に溶解し、アセトン中で再度沈殿させ、DI水に再度溶解して過剰の反応物を除去した。GMHEC溶液を凍結乾燥し、保存した。本実施例4において、HECをメタクリレート基で成功裏に誘導体化した。エオシンY開始系を用いた光重合は成功した。しかしながら、得られるGMHECヒドロゲルはGMHyヒドロゲルよりも硬く、かつ、脆かった。
[実施例4A]
1% Hyを室温で24時間、上記実施例4(反応XVIII)において使用した半分量のグリシジルメタクリレート、トリエチルアミン及びテトラブチルアンモニウムブロミドと水中で反応させた。反応を60℃で1時間継続した。反応後、溶液をアセトン中で沈殿させ、DI水に溶解し、アセトン中で再度沈殿させ、DI水に再度溶解して過剰の反応物を除去した。GMHEC溶液を凍結乾燥し、保存した。
以上に基づいて、反応I及び反応IVは、本発明の組成物において使用され得る生体適合性、かつ、生分解性の高分子キャリアを作製するための好ましい反応である。また、反応V及び反応XVIIIを使用しても、良好な特性を有する高分子キャリアが製造され得る。他のすべての反応は、上記のように、キャリアを合成する方法としてはあまり好ましくない。
[実施例5]
硬化深度データ、硬化ゲルの定性的な物性及び構成成分のFDA承認過程に基づいて、0.025mMエオシンY(EY)、100mMトリエタノールアミン(TEA)及び0.5% N−ビニルカプロラクタム(NVC)を含む開始系が最も好ましい。
[実施例6]
上記した組成物の圧縮率を、テクスチャ分析計を用いて測定した(n=4〜5)。結果を以下の棒グラフで示す。
本試験1において、GMHyキャリアは、実施例1(反応I)に記載した方法に従って合成された。重合系は配合O(表4、実施例5)とした。配合4及び配合7〜配合13(実施例6);配合4及び配合7〜配合13(実施例6)について試験した。結果を図1の棒グラフに示す。
本試験2において、実施例1(反応I)に記載した方法に従って、GMHyキャリアを合成した。重合系は配合O(表4、実施例5)とした。配合4及び配合7〜配合13(実施例6)について試験した。結果を図2の棒グラフに示す。
本試験3において、実施例1(反応I)に記載した方法に従って、GMHyキャリアを合成した。重合系は配合O(表4、実施例5)とした。配合4及び7(実施例6)について試験した。結果を図3の棒グラフに示す。
実施例1及び実施例2(反応I及び反応IV)に記載した方法に従って、GMHyキャリアを合成した。重合系は配合O(表4、実施例5)とした。配合4及び配合7〜配合9(実施例6)について試験した。結果を図4の棒グラフに示す。
検討1
4羽のニュージーランド(NZ)ウサギにおいて直径5mmの両側、単一脛骨欠損を創出した。GMHEC又はGMHyのいずれかのP−15細胞結合ペプチド(ABM/P−15)で覆われた無機質骨マトリクスから構成される光硬化性パテ材料を部位に移植した。移植片は可視光を用いて原位置で硬化させた。6週間後、組織診断及びX線撮影を行った。
第二の検討では、未硬化GMHy及び原位置で硬化したGMHyを用いた4週間での骨形成を、6羽のNZ白ウサギの大腿骨における両側直径2.0mmの欠損で比較した。
Claims (24)
- 新しい骨材料の成長を促進するための組成物であって、
無機質骨材料に由来する多孔性の再吸収性粒子、
重合時に安定なヒドロゲルマトリクスを形成し、かつ、前記粒子が該ヒドロゲル内部に分散される、重合性基を有する再吸収性の生体適合性キャリアゲル材料、及び
光で活性化されて前記キャリアゲル材料を重合する重合系、
からなる組成物。 - 前記粒子がウシ由来であり、かつ、前記粒子の平均粒径が約250μm〜約1000μmの範囲である、請求項1に記載の組成物。
- 前記粒子の平均粒径が約250μm〜約420μmの範囲である、請求項2に記載の組成物。
- 前記粒子の存在量が、前記組成物の重量に対して約30重量%〜約75重量%の範囲である、請求項1に記載の組成物。
- 前記粒子のかさ密度が約1.1〜約1.3g/ccであり、かつ、前記組成物が約40%〜約60%の粒子を含む、請求項4に記載の組成物。
- 前記キャリアゲルが光重合性多糖を含む、請求項1に記載の組成物。
- 前記キャリアゲルがメタクリル化ヒアルロン酸ナトリウムを含む、請求項6に記載の組成物。
- 前記キャリアゲルがメタクリル化ヒドロキシエチルセルロースを含む、請求項6に記載の組成物。
- 前記キャリアゲルが、メタクリル化ヒアルロン酸ナトリウム及びメタクリル化ヒドロキシエチルセルロースの混合物を含む、請求項6に記載の組成物。
- 前記キャリアゲルが約2重量%〜約10重量%の光重合性多糖を含む、請求項1に記載の組成物。
- 前記重合系が、エオシンY、アクリブラリン、チオニン、ローズベンガル、及びメチレンブルー染料、並びにそれらの混合物から成る群から選択される光重合開始剤を含む、請求項1に記載の組成物。
- 前記重合系が、約400〜約600nmの範囲の波長を有する青色の可視光によって活性化される、請求項1に記載の組成物。
- 前記重合系が、N−メチルジエタノールアミン、エチル4−(ジメチルアミノ)ベンゾエート(EDMAB)、2−[4−(ジメチルアミノ)フェニル]エタノール、N,N−ジメチル−p−トルイジン(DMPT)、ジヒドロキシエチル−p−トルイジン(DHEPT)、ビス(ヒドロキシエチル)−p−トルイジン、トリエタノールアミン(TEA)、及びそれらの混合物から成る群から選択される光重合促進剤を含む、請求項1に記載の組成物。
- 前記重合系が、N−ビニル−2−ピロリドン、N−ビニルカプロラクタム、及びそれらの混合物から成る群から選択される光重合促進剤を含む、請求項1に記載の組成物。
- 前記重合系が、エオシンY、トリエタノールアミン、及びN−ビニルカプロラクタムの配合物を含む、請求項1に記載の組成物。
- 新しい骨材料の成長を促進するための組成物であって、
P−15ポリペプチド材料と結合する、無機質骨材料に由来する多孔性の再吸収性粒子、
重合時に安定なヒドロゲルマトリクスを形成し、かつ、前記粒子が該ヒドロゲル内部に分散される、重合性基を有する再吸収性の生体適合性キャリアゲル材料、及び
光で活性化されて前記キャリアゲル材料を重合する重合系、
からなる組成物。 - 骨成長を誘導する組成物を欠損した骨組織に適用する方法であって、
a)無機質骨材料に由来する多孔性の再吸収性粒子;重合時に安定なヒドロゲルマトリクスを形成し、かつ、前記粒子が該ヒドロゲル内部に分散される、重合性基を有する再吸収性の生体適合性キャリアゲル材料;及び、光で活性化されて前記キャリアゲル材料を重合する重合系からなる、骨成長を誘導する組成物を用意する工程、
b)前記組成物を欠損した骨組織へ適用する工程、及び
c)前記組成物が硬化するように、前記組成物に光を照射する工程、
からなる方法。 - 前記組成物がパテ様の粘稠性を有し、かつ、光を照射する前に、前記欠損した骨組織全体に渡って成形される、請求項17に記載の方法。
- 前記粒子がウシ由来であり、かつ、前記粒子の平均粒径が約250μm〜約1000μmの範囲である、請求項17に記載の方法。
- 前記キャリアゲルがメタクリル化ヒアルロン酸ナトリウムを含む、請求項17に記載の方法。
- 前記キャリアゲルがメタクリル化ヒドロキシエチルセルロースを含む、請求項17に記載の方法。
- 前記組成物に、約400〜約600nmの範囲の波長を有する青色の可視光を照射する、請求項17に記載の方法。
- 前記重合系が、エオシンY、トリエタノールアミン、及びN−ビニルカプロラクタムの配合物を含む、請求項17に記載の方法。
- P−15ポリペプチド材料が前記無機質骨材料に由来する前記粒子と結合する、請求項17に記載の方法。
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US75445305P | 2005-12-28 | 2005-12-28 | |
PCT/US2006/049198 WO2007079053A2 (en) | 2005-12-28 | 2006-12-22 | Light-curable bone growth material for treating dental bone defects |
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JP2008548665A Pending JP2009522001A (ja) | 2005-12-28 | 2006-12-22 | 歯の骨の欠損を治療するための光硬化性骨成長材料 |
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US (4) | US20070269518A1 (ja) |
EP (1) | EP1973513B1 (ja) |
JP (1) | JP2009522001A (ja) |
AT (1) | ATE487459T1 (ja) |
CA (1) | CA2634245C (ja) |
DE (1) | DE602006018196D1 (ja) |
WO (1) | WO2007079053A2 (ja) |
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WO2009155583A1 (en) * | 2008-06-19 | 2009-12-23 | The Trustees Of The University Of Pennsylvania | Biomaterials for tissue replacement |
GB0813659D0 (en) | 2008-07-25 | 2008-09-03 | Smith & Nephew | Fracture putty |
US9193948B2 (en) * | 2008-11-12 | 2015-11-24 | The Trustees Of The University Of Pennsylvania | Biomaterials for tissue replacement |
WO2011031876A1 (en) | 2009-09-09 | 2011-03-17 | Qd Vision, Inc. | Formulations including nanoparticles |
EP2475717A4 (en) | 2009-09-09 | 2015-01-07 | Qd Vision Inc | PARTICLES WITH NANOPARTICLES, USES THEREOF AND METHOD THEREFOR |
BR112012026372A2 (pt) | 2010-04-16 | 2016-08-02 | Apatech Ltd | material biocompatível, método para fabricar um material, e, matriz polimérica reabsorvível |
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US10507178B2 (en) * | 2015-05-06 | 2019-12-17 | Research Foundation Of The City University Of New York | Method for treating intervertebral disc degeneration |
CA3177726A1 (en) | 2015-05-21 | 2016-11-24 | Musculoskeletal Transplant Foundation | Modified demineralized cortical bone fibers |
EP3302588A4 (en) * | 2015-05-29 | 2019-01-23 | Launchpad Medical, LLC | COMPOSITIONS AND METHODS FOR ADHESION TO SURFACES |
CN108676178B (zh) * | 2018-04-26 | 2021-02-09 | 济南大学 | 改性多糖水凝胶的制备方法及制备的改性多糖水凝胶 |
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Also Published As
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US20070269518A1 (en) | 2007-11-22 |
US20120129134A1 (en) | 2012-05-24 |
US20100034883A1 (en) | 2010-02-11 |
CA2634245A1 (en) | 2007-07-12 |
WO2007079053A2 (en) | 2007-07-12 |
WO2007079053A3 (en) | 2008-07-31 |
EP1973513A2 (en) | 2008-10-01 |
CA2634245C (en) | 2013-12-10 |
DE602006018196D1 (de) | 2010-12-23 |
EP1973513B1 (en) | 2010-11-10 |
ATE487459T1 (de) | 2010-11-15 |
US20110045084A1 (en) | 2011-02-24 |
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