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

为了开发生物可吸收防粘附膜材料，合成了两亲ABA型三嵌段共聚物。A段为聚[L-丙交酯(LA)-r-脱脂肽](聚[LA-r-(Glc-Leu)]：PLGL或聚[LA-r-(Glc-Phe)]：PlGF)，B段为聚乙二醇组分(Mn=10,000和Mn=20,500)。以2-乙基己酸锡为催化剂，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-PEGPLGL和PLGF-PEGPLGF)。为了评价该共聚物作为生物可吸收防粘附膜的候选性能，本研究考察了PLGL-PEG-PLGL和PLGF-PEG-PLGF膜在生理条件下的降解行为和吸水行为，并与聚乳酸-聚乙二醇聚乳酸(PLLA-PEG-PLLA)三嵌段共聚物进行了比较。与PLGL-PEG-PLGL膜和PLLA-PEG-PLLA相比，PLGF-PEG-PLGF膜具有更高的弹性模量和更长的断裂伸长率。PLGL-PEG-PLGL和PLGF-PEG-PLGF膜的降解速率可以通过控制亲水性B链段的相对分子质量和A链段的脱脂肽单元含量等分子结构来改变。PLGF-PEG-PLGF膜的降解率略高于具有相似分子量和去脂肽单元含量的PLGL-PEG-PLGL膜。并对PLGL-PEG-PLGL膜的生物相容性和体内吸收行为进行了评价。这些薄膜被植入ddy小鼠的皮下。结果表明，PLGL-PEG-PLGL膜在体内逐渐吸收，无炎症反应。

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.