Long-Term In Virto Hydrolytic Degradation Behavior and Mechanism of Biodegradable Poly(L-lactic acid)

可生物降解聚L-乳酸的长期体外水解降解行为及机理

基本信息

批准号：
16500291
负责人：
TSUJI Hideto
金额：
$ 2.3万
依托单位：
Toyohashi University of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

The purpose of this project is to elucidate the long-term in vitro hydrolytic degradation behavior and mechanism of PLLA crystalline residues (extended chain crystallites). For this purpose, PLLA crystalline residues were prepared by crystallization of PLLA films and subsequent accelerated hydrolytic degradation at 97℃ for 40 hours and the obtained crystalline residues were hydrolytically degraded at different conditions at pH 7.4 and different temperatures of 37, 50, 70, and 97℃ up to 512 days, at 37℃ at different pH of-0.9, 0.2, 7.4,11.7, and 12.8, and at pH8.6 and 37℃ in the presence of proteinase K. Also, the hydrolytic degradation behavior of L-lactic acid copolymers of poly(L-lactide-co-glycolide) (81:19) [P(LLA-GA)], poly(L-lactide-ε-caprolactone) (77/23) [P(LLA-CL)],and poly(L-lactide-co-D-lactide)] (77:23) (98.8:1.2) [P(LLA-DLA)] and their crystalline residues formed during hydrolytic degradation was monitored. The formation and hydrolytic degradation of the crystalline residu … More es were traced by gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). The following results were obtained. (1) For all conditions, the crystalline residues are hydrolytically degraded linearly with degradation time from the chain terminals at the folding surface; (2) The activation energy for hydrolytic degradation (ΔE_h) of the crystalline residues at pH 7.4 was estimated to be 75.2 kJ mol^<-1>. This is much higher than 50.9 kJ mol^<-1> of ΔE_h reported for PLLA in the melt and indicates that higher hydrolytic degradation-resistance of the crystalline residues; (3) Acidic and alkaline conditions as well as high temperature enhanced the hydrolytic degradation of the crystalline residues, whereas proteinase K has no catalytic effect, revealing that the insignificant enzymatic activity of proteinase K for the PLLA chains neighboring on the crystalline regions. (4) The crystalline residues were formed and hydrolytically degraded in P(LLA-GA) and P(LLA-CL) films within the periods of 24 weeks, whereas in the case of PLLA and P(LLA-DLA) (98.8:1.2) films, neither formation nor hydrolytic degradation of crystalline residues took place within the degradation period of 50 weeks. Less

本项目的目的是阐明PLLA结晶残渣（延长链微晶）的长期体外水解降解行为和机理为此，通过PLLA薄膜结晶并随后在97℃加速水解降解来制备PLLA结晶残渣。 ℃反应40小时，得到的结晶残渣在pH 7.4、37、50、37、50等不同条件下进行水解降解。 70和97℃长达512天，37℃，不同pH值-0.9、0.2、7.4、11.7和12.8，以及pH8.6和37℃，在蛋白酶K存在下。此外，水解降解行为L-乳酸聚（L-丙交酯-共-乙交酯）共聚物（81:19） [P(LLA-GA)]、聚(L-丙交酯-ε-己内酯) (77/23) [P(LLA-CL)] 和聚(L-丙交酯-共-D-丙交酯)] (77: 23) (98.8:1.2) [P(LLA-DLA)] 及其在水解降解过程中形成的结晶残留物对结晶残留物的形成和水解降解进行了监测。通过凝胶渗透色谱 (GPC) 和差示扫描量热法 (DSC) 进行追踪，得到以下结果 (1) 在所有条件下，结晶残留物从折叠表面的链末端开始线性水解降解； ))在pH 7.4下结晶残余物的水解降解活化能(ΔE_h)估计为75.2kJ mol^<-1>，这很大。熔体中 PLLA 的 ΔE_h 高于 50.9 kJ mol^-1>，表明结晶残留物具有更高的水解降解能力；（3）酸性和碱性条件以及高温增强了结晶的水解降解。残基，而蛋白酶 K 没有催化作用，这表明蛋白酶 K 对邻近结晶区的 PLLA 链的酶活性不显着。 (4) P(LLA-GA) 和 P(LLA-CL) 薄膜在 24 周内形成结晶残留物并水解降解，而 PLLA 和 P(LLA-DLA) (98.8:1.2) ）薄膜，在50周的降解期内既没有形成结晶残留物，也没有发生水解降解。