JP6757329B2 - 自己組み込み型ヒドロゲル及びその製造方法 - Google Patents
自己組み込み型ヒドロゲル及びその製造方法 Download PDFInfo
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- JP6757329B2 JP6757329B2 JP2017551641A JP2017551641A JP6757329B2 JP 6757329 B2 JP6757329 B2 JP 6757329B2 JP 2017551641 A JP2017551641 A JP 2017551641A JP 2017551641 A JP2017551641 A JP 2017551641A JP 6757329 B2 JP6757329 B2 JP 6757329B2
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- hydrogel
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- pyrimidinone
- ureido
- water
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Description
本出願は、2015年4月2日に出願された米国仮出願第62/142,256号の利益を主張し、当該仮出願は、参照によりその全体が本明細書に援用される。
本発明は、米国国立衛生研究所(NIH)及び米国国立歯科衛生研究所(the National Institute of Dental and Craniofacial Research) (NIDCR)によって契約された助成番号DE015384、DE017689及びDE022327、及び米国科学財団(NSF)によって契約された助成番号DMR-1206575、及び米国国防総省(DoD)によって契約された助成番号W81XWH-12-2-0008の下、政府の支援を受けてなされたものである。政府は、本発明において一定の権利を保有する。
再生医療技術は、三次元(3D)テンプレートの役割を果たすことができる足場材料、及び/又はドラッグデリバリー機構の役割を果たすことができる薬物担体を利用することが多い。組織再生は、組織が喪失又は罹患した患者に対する潜在的な処置であり得る。しかしながら、2種類以上の組織からなる組織複合体の再生は、組織設計に課題を提示する。
本明細書には、組織工学、ドラッグデリバリー、組織バルキング(tissue bulking)、接着剤、化粧料、創傷被覆材及び縫合剤を含む、種々の用途に用いることが可能な自己組込み型ヒドロゲルが開示されている。単一の組織又は多組織複合体は、本明細書に開示されているヒドロゲルを用いて再生し得る(may by regenerated)。ヒドロゲルは、適切な細胞及び/又は生体分子がその中に組み込まれ/封入された後、穏やかな条件下で自己組み込みすることができる。これによって、空間的に画定された領域における組織(場合によっては、複数の種類の組織)を再生し、さらに、組織をシームレスに一体化することもできる。本明細書に示されている一部の例は、骨-軟骨組織複合体の再生を示し、これは、自然の組織生着(native tissue integration)に似ている。ただし、自己組込み型ヒドロゲルの用途は、これらの例に限定されず、自己組込み型ヒドロゲルは、種々の組織複合体を設計する可能性を有している。
実施例1
Claims (11)
- 自己組み込み型ヒドロゲルであって、
水溶性高分子を含み、該水溶性高分子が、
酸素原子又は窒素原子を含む、少なくとも1個の官能基を有する繰り返し単位であって、少なくとも1つのグルコース単位又2つのβ(1→4)結合D-グルコース単位が含まれる繰り返し単位と、
前記繰り返し単位の前記少なくとも1個の官能基である酸素原子又は窒素原子に共有結合し、ウレイド-ピリミジノンを含むペンダント分子鎖と、
を含む前記自己組み込み型ヒドロゲル。 - 前記ヒドロゲルがコア-シェル構造を有さない、請求項1に記載の自己組み込み型ヒドロゲル。
- 前記水溶性高分子が修飾デキストランであり、前記繰り返し単位が、少なくとも1つのグルコース単位を含有する、請求項1に記載の自己組み込み型ヒドロゲル。
- 前記水溶性高分子が修飾セルロースであり、前記繰り返し単位には、2つのβ(1→4)結合D-グルコース単位が含まれる、請求項1に記載の自己組み込み型ヒドロゲル。
- 前記ペンダント分子鎖には、前記ウレイド-ピリミジノンを、前記繰り返し単位の前記少なくとも1個の官能基である酸素原子、硫黄原子又は窒素原子に結合させるイソシアネートが含まれる、請求項1に記載の自己組み込み型ヒドロゲル。
- 前記ペンダント分子鎖には、前記ウレイド- ピリミジノンを、前記繰り返し単位の前記少なくとも1個の官能基である酸素原子、硫黄原子又は窒素原子に結合させる、活性化エステル、エポキシ基又は塩化アシル基が含まれる、請求項1に記載の自己組み込み型ヒドロゲル。
- 前記ウレイド- ピリミジノンの置換密度が8.1以下である、請求項1に記載の自己組み込み型ヒドロゲル。
- 水溶性高分子の主鎖に結合したヒドロキシル基又はアミン基に、ウレイド-ピリミジノン-イソシアネートをグラフト化させることによって、前記ウレイド-ピリミジノン-イソシアネートを含むペンダント分子鎖を形成することを含み、前記水溶性高分子はデキストラン又はセルロースから選ばれる、自己組み込み型ヒドロゲルの製造方法。
- イソシアネートを2-アミノ-4-ヒドロキシ-6-メチルピリミジンと反応させることによって、ウレイド-ピリミジノン-イソシアネートを形成することを、さらに含む、請求項8に記載の方法。
- 水溶性高分子を第1の溶媒中に溶解して、第1の溶液を形成することと、
前記ウレイド-ピリミジノン-イソシアネートを第2の溶媒中に溶解して、第2の溶液を形成することと、
前記第1の溶液の少なくとも一部を前記第2の溶液と混合して、混合物を形成することと、
撹拌下で前記混合物に触媒を加えることと、
前記混合物を所定の温度で所定の時間硬化させて、自己組み込み型ヒドロゲルを形成することと、
前記自己組み込み型ヒドロゲルを溶媒交換過程に暴露することと、
をさらに含む、請求項9に記載の方法。 - 前記水溶性高分子に対する前記ウレイド-ピリミジノン-イソシアネートの供給比を変更することによって、ウレイド-ピリミジノンの置換密度を制御すること、をさらに含む、請求項8に記載の方法。
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DE17689C (de) | C. KESSELER in Berlin W., Mohrenstr. 63 | Neuerungen an einer Befestigung der Bandagen bei Wagenrädern für Eisenbahnzwecke | ||
DE15384C (de) | C. W. muchall in Wiesbaden | Brennergallerie mit Centrirungsfedern und Kombination eines Schirmreflektors mit dem äufseren Cylinder für Doppelcylinderlampen | ||
DE22327C (de) | L. VESSIER in Lequin in Soulaines | Stechheber | ||
JP2001172358A (ja) * | 1999-12-15 | 2001-06-26 | Sumitomo Seika Chem Co Ltd | ゲル化基材 |
ES2376888T3 (es) * | 2005-05-04 | 2012-03-20 | Suprapolix B.V. | Materiales supramoleculares activos biológicamente, modulares biorreabsorbibles o biomédicos |
ATE512200T1 (de) * | 2005-05-04 | 2011-06-15 | Suprapolix Bv | Hydrogele mit wasserstoffbrückenbindungen |
US8628789B2 (en) * | 2007-03-23 | 2014-01-14 | Suprapolix, B.V. | Strong reversible hydrogels |
WO2012168392A1 (en) * | 2011-06-07 | 2012-12-13 | Technische Universiteit Eindhoven | Hydrogelator with shape-memory properties |
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2016
- 2016-04-01 JP JP2017551641A patent/JP6757329B2/ja not_active Expired - Fee Related
- 2016-04-01 WO PCT/US2016/025637 patent/WO2016161327A1/en active Application Filing
- 2016-04-01 CN CN201680030996.8A patent/CN107636049B/zh active Active
- 2016-04-01 EP EP16774340.0A patent/EP3277745A4/en active Pending
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2017
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WO2016161327A1 (en) | 2016-10-06 |
CN107636049B (zh) | 2020-12-25 |
EP3277745A1 (en) | 2018-02-07 |
JP2018517004A (ja) | 2018-06-28 |
EP3277745A4 (en) | 2018-12-12 |
US20180094106A1 (en) | 2018-04-05 |
US10513587B2 (en) | 2019-12-24 |
CN107636049A (zh) | 2018-01-26 |
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