止血、癒着防止、抗菌効果を併せ持った新規ｉｎｊｅｃｔａｂｌｅゲルの開発

开发具有止血、防粘连、抗菌作用的新型注射凝胶

• 批准号: 19F19061
• 负责人: 伊藤 大知
• 金额: $ 1.47万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2019
• 资助国家: 日本
• 起止时间: 2019-04-25 至 2021-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19F19061/
• 关键词: hydrogels; antiadhesion barrier; dextran; PEG; hyaluronan; Anti-adhesion; Hemostatic; Injectable; Hydrogel; Biocompatible

We have developed an injectable hydrogel via Dex-g-PDPMA-g-SRT crosslinked with Cl-PEG-Cl. Partially oxidized Dextran was grafted with Poly[2 (Dimethylamino)ethyl Methacrylate] (PDMAEMA) by ATRP to form Dex-g-PDMAEMA. Serotonin (SRT) was reacted with partially oxidized aldehyde containing Dex-g-PDMAEMA to form SRT-g-Dex-PDMAEMA, and chloride terminated poly(ethylene glycol) (Cl-PEG-Cl)was prepared 4-chloromethyl benzoyl chloride by the esterification reaction. The chemically crosslinked hydrogel was obtained, by the reaction between tertiary amine group of PDMAEMA and chloride terminated PEG. The gelation time of the hydrogel was 2-5 min its basically depends on concentration of the prepolymers solution and temperature. The In-vivo hemostatic behavior of hydrogel was evaluated using mice liver hemorrhage model. The hydrogel showed excellent hemostatic capacity in comparison to control. The hemostatic behavior of the hydrogel due to two component first formation of permanent positive charge on tertiary amine of PDMAEMA upon crosslinking and second one is pendent serotonin moiety. The hydrogel was compared with marketed hemostatic product TachoSil; and SURGICEL; using mice liver hemorrhage model. The hydrogel follows dual hemostatic mechanism, because it contains permanent cationic change that interact with red blood cells and serotonin moiety interact with platelet and accelerate the hemostasis synergistically.

我们已经开发了一种可注射的水凝胶，通过Dex-g-PDPMA-g-SRT与Cl-PEG-Cl交联。采用原子转移自由基聚合法（ATRP）将部分氧化的右旋糖酐（Dexan）接枝到聚甲基丙烯酸二甲氨基乙酯（PDMAEMA）上，得到Dex-g-PDMAEMA。以5-羟色胺（SRT）为原料，与部分氧化的Dex-g-PDMAEMA醛反应，合成SRT-g-Dex-PDMAEMA，再与4-氯甲基苯甲酰氯进行酯化反应，合成端氯聚乙二醇（Cl-PEG-Cl）。通过PDMAEMA的叔胺基团与氯化物封端的PEG反应，得到化学交联水凝胶。水凝胶的凝胶化时间为2-5 min，其基本上取决于预聚物溶液的浓度和温度。采用小鼠肝出血模型评价水凝胶的体内止血性能。与对照相比，水凝胶显示出优异的止血能力。水凝胶的止血行为归因于两种组分，第一种是交联时在PDMAEMA的叔胺上形成永久正电荷，第二种是侧链5-羟色胺部分。使用小鼠肝出血模型将水凝胶与市售止血产品TachoSil和SURGICEL进行比较。水凝胶遵循双重止血机制，因为它含有与红细胞相互作用的永久阳离子变化和与血小板相互作用的5-羟色胺部分，并协同加速止血。

项目成果

Development of N, N dimethyl propyl amine conjugated hyaluronic acid zwitterionic hydrogel

N,N二甲基丙胺共轭透明质酸两性离子水凝胶的研制

• 发表时间: 2019
• 作者: Qi Pan;Zheng Ying Grace;Ohta Seiichi;Kokudo Norihiro;Hasegawa Kiyoshi;Ito Taichi;Chandel Arvind Kumar Singh・Taichi Ito;Chandel Arvind Kumar Singh・Ito Taichi;Pan Qi・Seiichi OHTA・Ayano FUJISAWA・Yosuke TSUJI・Mitsuhiro FUJISHIRO・Taichi ITO;石田 康博;伊藤大知;石田 康博;Chandel Arvind Kumar Singh・Ohta Seiichi・Ito Taichi
• 通讯作者: Chandel Arvind Kumar Singh・Ohta Seiichi・Ito Taichi

Spray application of in situ cross-linkable powders for preventing esophageal stenosis after endoscopic submucosal dissection

原位交联粉末喷雾预防内镜黏膜下剥离术后食管狭窄

• 发表时间: 2019
• 作者: Qi Pan;Zheng Ying Grace;Ohta Seiichi;Kokudo Norihiro;Hasegawa Kiyoshi;Ito Taichi;Chandel Arvind Kumar Singh・Taichi Ito;Chandel Arvind Kumar Singh・Ito Taichi;Pan Qi・Seiichi OHTA・Ayano FUJISAWA・Yosuke TSUJI・Mitsuhiro FUJISHIRO・Taichi ITO
• 通讯作者: Pan Qi・Seiichi OHTA・Ayano FUJISAWA・Yosuke TSUJI・Mitsuhiro FUJISHIRO・Taichi ITO

Zwitterionic hyaluronic acid-DMPA hydrogel for biomedical application

两性离子透明质酸-DMPA水凝胶的生物医学应用

• 发表时间: 2020
• 作者: Qi Pan;Zheng Ying Grace;Ohta Seiichi;Kokudo Norihiro;Hasegawa Kiyoshi;Ito Taichi;Chandel Arvind Kumar Singh・Taichi Ito
• 通讯作者: Chandel Arvind Kumar Singh・Taichi Ito

Preparation of injectable hydrogel based on Dextran-g-PDMAEMA-g-Serotonin for hemostasis

基于Dextran-g-PDMAEMA-g-Serotonin的止血注射水凝胶的制备

• 发表时间: 2020
• 作者: Qi Pan;Zheng Ying Grace;Ohta Seiichi;Kokudo Norihiro;Hasegawa Kiyoshi;Ito Taichi;Chandel Arvind Kumar Singh・Taichi Ito;Chandel Arvind Kumar Singh・Ito Taichi
• 通讯作者: Chandel Arvind Kumar Singh・Ito Taichi

癒着防止材の開発と応用展開

防粘连材料的开发及应用

• 发表时间: 2019
• 作者: Qi Pan;Zheng Ying Grace;Ohta Seiichi;Kokudo Norihiro;Hasegawa Kiyoshi;Ito Taichi;Chandel Arvind Kumar Singh・Taichi Ito;Chandel Arvind Kumar Singh・Ito Taichi;Pan Qi・Seiichi OHTA・Ayano FUJISAWA・Yosuke TSUJI・Mitsuhiro FUJISHIRO・Taichi ITO;石田 康博;伊藤大知
• 通讯作者: 伊藤大知