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Application of Bioabsorbable Block Copolymers Containing Poly(Ethylene Glycol) as Medical Materials

含聚乙二醇生物可吸收嵌段共聚物作为医用材料的应用

基本信息

批准号：
15300172
负责人：
OHYA Yuichi
金额：
$ 9.79万
依托单位：
Kansai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

In order to develop material for bioabsorbable anti-adhesive membrane, amphiphilic ABA-type triblock copolymers were synthesized. A segment is poly[L-lactide(LA)-r-depsipeptide] (poly[LA-r-(Glc-Leu)] : PLGL or poly[LA-r-(Glc-Phe)] : PLGF) and B segment is poly(ethylene glycol) (PEG) (Mn=10,000 and Mn=20,500). The synthesis of the triblock copolymer (PLGL-PEG-PLGL and PLGF-PEG-PLGF) was carried out via ring-opening copolymerization of L-lactide and cyclo(Glc-Leu) or cyclo(Glc-Phe) in the presence of hydroxytelechelic poly(ethylene glycol) using tin 2-ethylhexanoate as a catalyst. In this study, to evaluate the copolymers as a candidate for bioabsorbable anti-adhesive membrane, physicochemical properties such as degradation behavior under physiological condition and water absorption behavior of PLGL-PEG-PLGL and PLGF-PEG-PLGF films were investigated and compared with polylactide-PEG-polylactide (PLLA-PEG-PLLA) triblock copolymer. The PLGF-PEG-PLGF films showed higher Young's modulus and longer elongation to break than PLGL-PEG-PLGL films and PLLA-PEG-PLLA. The degradation rate of PLGL-PEG-PLGL and PLGF-PEG-PLGF films could be varied by controlling the molecular architectures, such as molecular weight of hydrophilic B segment and depsipeptide unit content in A segment. The degradation rate of PLGF-PEG-PLGF films was slightly higher than that of PLGL-PEG-PLGL films having similar molecular weight and content of depsipeptide unit. The biocompatibility and absorption behavior of the PLGL-PEG-PLGL films were also evaluated in vivo. The films were implanted subcutaneously into ddy-mice. The results showed that the PLGL-PEG-PLGL films were absorbed gradually in vivo without inflammation.

为了开发生物可吸收防粘膜材料，合成了两亲性ABA型三嵌段共聚物。 A片段是聚[L-丙交酯(LA)-r-缩肽](聚[LA-r-(Glc-Leu)]：PLGL或聚[LA-r-(Glc-Phe)]：PLGF)，B片段是聚(乙二醇)(PEG)(Mn=10,000和Mn=20,500)。以2-乙基己酸锡为催化剂，在羟基遥爪聚乙二醇存在下，通过L-丙交酯与环(Glc-Leu)或环(Glc-Phe)的开环共聚合成了三嵌段共聚物(PLGL-PEG-PLGL和PLGF-PEG-PLGF)。在本研究中，为了评估该共聚物作为生物可吸收防粘膜的候选材料，研究了PLGL-PEG-PLGL和PLGF-PEG-PLGF薄膜的物理化学性质，例如生理条件下的降解行为和吸水行为，并与聚丙交酯-PEG-聚丙交酯（PLLA-PEG-PLLA）三嵌段共聚物进行比较。 PLGF-PEG-PLGF 薄膜比 PLGL-PEG-PLGL 薄膜和 PLLA-PEG-PLLA 表现出更高的杨氏模量和更长的断裂伸长率。 PLGL-PEG-PLGL和PLGF-PEG-PLGF薄膜的降解速率可以通过控制分子结构来改变，例如亲水性B片段的分子量和A片段中的缩酚肽单元含量。 PLGF-PEG-PLGF膜的降解率略高于具有相似分子量和缩酚肽单元含量的PLGL-PEG-PLGL膜。 PLGL-PEG-PLGL 薄膜的生物相容性和吸收行为也在体内进行了评估。将薄膜植入干鼠皮下。结果表明，PLGL-PEG-PLGL膜在体内逐渐被吸收，且无炎症反应。