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

本项目的目的是阐明PLLA结晶残留物(扩链微晶)的长期体外降解行为和机理。为此，通过将聚乳酸薄膜结晶，然后在97℃下加速降解40h，制备了聚乳酸结晶残留物，并在不同条件下，在pH值为7.4、37、50、70和97℃的不同条件下，在37℃、-0.9、0.2、7.4、11.7和12.8的不同pH下，在蛋白酶K的存在下，在pH值为8.6和37℃的条件下，进行了长达512天的降解。研究了L-乳酸共聚物(P(L-丙交酯-乙交酯)(81：19)[P(L LA-GA)]、聚(L-丙交酯-ε-己内酯)(77/23)[P(L LA-CL)]和聚(L-丙交酯-D-丙交酯)](77：23)(98.8：1.2)[P(L LA-DLA)]及其在水解降解过程中形成的结晶残基的水解降解行为。结晶残留物…的形成与降解凝胶渗透色谱(GPC)和差示扫描量热法(DSC)检测到更多的ES。得到了以下结果。(1)在所有条件下，结晶残基从折叠表面的链端开始随降解时间线性降解：(2)在pH值为7.4时，结晶残基的水解降解活化能(ΔE_h)为75.2kJ·mol~(-1)~(-1)·g~(-1)。这远高于ΔE_h报道的熔体中PLLA的50.9kJ·mol~(-1)~(-1)&gt~(-1)，表明结晶残留物具有较高的耐水解性；(3)酸性和碱性条件以及高温促进了结晶残留物的水解性降解，而蛋白酶K没有催化作用，表明蛋白酶K对邻近结晶区的PLLA链的酶活性不明显。(4)P(LLA-GA)和P(LLA-CL)膜在24周内形成结晶残留物并进行降解，而PLLA和P(LLA-DLA)(98.8：1.2)膜在50周内既没有形成结晶残留物，也没有发生水解性降解。较少

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