JP6355959B2 - 機能性架橋構造体及びその製造方法並びに医療材料 - Google Patents
機能性架橋構造体及びその製造方法並びに医療材料 Download PDFInfo
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- JP6355959B2 JP6355959B2 JP2014089840A JP2014089840A JP6355959B2 JP 6355959 B2 JP6355959 B2 JP 6355959B2 JP 2014089840 A JP2014089840 A JP 2014089840A JP 2014089840 A JP2014089840 A JP 2014089840A JP 6355959 B2 JP6355959 B2 JP 6355959B2
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Description
項1. OH基及びアミノ基からなる群から選ばれる少なくとも1種とCOOH基を繰り返し単位に有する天然高分子を水中で水溶性脱水縮合剤の存在下にOH基又はアミノ基を有する生理活性物質と反応させて、天然高分子のCOOH基とエステル結合又はアミド結合を介して生理活性物質を結合し、かつ、前記天然高分子の架橋反応を行うことを特徴とする、機能性架橋構造体の製造方法。
項2. 水溶性脱水縮合剤が、トリアジン系縮合剤及び水溶性カルボジイミド類からなる群から選ばれることを特徴とする項1に記載の機能性架橋構造体の製造方法。
項3. 生理活性物質がカテキン類、ポリフェノール類、プロアントシアニジン、アントシアニン、フラボノイド類、大豆イソフラボン類及びポリアミンからなる群から選ばれる少なくとも1種である、項1又は2に記載の機能性架橋構造体の製造方法。
項4. 天然高分子がヒアルロン酸、コラーゲン、ゼラチン、キサンタンガム、ジェランガム、ペクチン/ペクチン酸、アルギン酸又はそのナトリウム塩、エラスチンからなる群から選ばれる、項1〜3のいずれかに記載の機能性架橋構造体の製造方法。
項5. OH基及びアミノ基からなる群から選ばれる少なくとも1種とCOOH基を繰り返し単位に有する天然高分子と、OH基又はアミノ基を有する生理活性物質がエステル結合又はアミド結合で結合され、かつ、天然高分子のCOOH基と天然高分子のOH基及びアミノ基からなる群から選ばれる少なくとも1種が架橋している、機能性架橋構造体。
項6. 項5記載の機能性架橋構造体を含む医療材料。
豚ゼラチン(Sigma−Aldrich社製)100mgを水5mlに50℃で溶解し、N−メチルモルホリン(27.5μl)、EGCG(0.7mg)、DMT−MM(69.2mg)を加え、室温で24時間撹拌した。
ゼラチン水溶液を常法に従い真空熱脱水し、ゼラチンスポンジを得た。
豚ゼラチン(Sigma−Aldrich社製)100mgを水5mlに50℃で溶解し、N−メチルモルホリン(27.5μl)、EGCG(0.7mg)を加え、室温で24時間撹拌した。得られた溶液を、透析膜としてRC透析チューブ ポア7 MWCO1000(Spectrum社製)を使用し、水に対し24時間透析して凍結乾燥すると、EGCGが含まれないゼラチンが得られた。
直径4.2mmのトレフィンバーを用いマウスの頭蓋冠に臨界骨欠損を作製し、実施例1で得られたEGCGが結合した架橋ゼラチンスポンジ及び比較例1で得た真空熱脱水スポンジを当該欠損箇所に埋入した。4週間後の骨欠損箇所の状態を図2に示す。
ヒアルロン酸(ナカライテスク社製)50mgを水5mlに室温で溶解し、N−メチルモルホリン(13.7μl)、EGCG(0.5mg)、DMT−MM(34.6mg)を加え、室温で24時間撹拌した。
キサンタンガム(東京化成社製)100mgを水25mlに室温で溶解し、N−メチルモルホリン(27.5μl)、EGCG(0.7mg)、DMT−MM(69.2mg)を加え、室温で24時間撹拌した。
Claims (6)
- OH基及びアミノ基からなる群から選ばれる少なくとも1種とCOOH基を繰り返し単位に有する天然高分子を水中で水溶性脱水縮合剤の存在下にOH基又はアミノ基を有する生理活性物質と反応させて、天然高分子のCOOH基とエステル結合又はアミド結合を介して生理活性物質を結合し、かつ、前記天然高分子の架橋反応を行うことを特徴とする、機能性架橋構造体の製造方法であって、前記天然高分子がヒアルロン酸、コラーゲン、ゼラチン又はキサンタンガムであり、前記生理活性物質がカテキン(C)、ガロカテキン(GC)、エピカテキン(EC)、エピガロカテキン(EGC)、カテキンガレート(CG)、エピカテキンガレート(ECG)、ガロカテキンガレート(GCG)、エピガロカテキンガレート(EGCG)からなる群から選ばれる少なくとも1種のカテキン類である、機能性架橋構造体の製造方法。
- 水溶性脱水縮合剤が、トリアジン系縮合剤及び水溶性カルボジイミド類からなる群から選ばれることを特徴とする請求項1に記載の機能性架橋構造体の製造方法。
- 生理活性物質がエピガロカテキンガレート(EGCG)である、請求項1又は2に記載の機能性架橋構造体の製造方法。
- 天然高分子がヒアルロン酸、ゼラチン又はキサンタンガムである、請求項1〜3のいずれかに記載の機能性架橋構造体の製造方法。
- OH基及びアミノ基からなる群から選ばれる少なくとも1種とCOOH基を繰り返し単位に有する天然高分子と、OH基又はアミノ基を有する生理活性物質がエステル結合又はアミド結合で結合され、かつ、天然高分子のCOOH基と天然高分子のOH基及びアミノ基からなる群から選ばれる少なくとも1種が架橋している、機能性架橋構造体であって、前記天然高分子がヒアルロン酸、ゼラチン又はキサンタンガムであり、前記生理活性物質がエピガロカテキンガレート(EGCG)である、機能性架橋構造体。
- 請求項5記載の機能性架橋構造体を含む医療材料。
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