止血、癒着防止、抗菌効果を併せ持った新規ｉｎｊｅｃｔａｂｌｅゲルの開発

我们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。将部分氧化的葡聚糖与聚[2（二甲氨基）甲基丙烯酸乙酯]（PDMAEMA）通过ATRP接枝得到Dex-g-PDMAEMA。将5 -羟色胺（SRT）与含有Dex-g-PDMAEMA的部分氧化醛反应生成SRT-g- dex - pdmaema，并通过酯化反应得到端氯聚乙二醇（Cl-PEG-Cl）。通过PDMAEMA的叔胺基与氯化端聚乙二醇反应，得到化学交联水凝胶。水凝胶的凝胶时间为2-5 min，主要取决于预聚体溶液的浓度和温度。采用小鼠肝出血模型评价水凝胶的体内止血作用。与对照组相比，水凝胶表现出优异的止血能力。水凝胶的止血行为是由于两种成分：一是交联时PDMAEMA叔胺上形成永久正电荷，二是依赖血清素部分。将水凝胶与市售止血产品TachoSil进行比较；和SURGICEL;采用小鼠肝出血模型。该水凝胶具有双重止血机制，它含有与红细胞相互作用的永久性阳离子变化和血清素部分与血小板相互作用，协同加速止血。

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.