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

本课题旨在阐明PLLA结晶残留物（扩链微晶）的长期体外水解降解行为和机理。为此目的，通过PLLA膜的结晶和随后在97℃下加速水解降解40小时来制备PLLA结晶残余物，并且所获得的结晶残余物在不同条件（pH 7.4和不同温度37、50、70和97℃）下水解降解长达512天，在37℃下在不同pH-0.9，0.2，7.4，11.7和12.8;在pH8.6和37℃条件下，蛋白酶K存在下，此外，监测了聚（L-丙交酯-共-乙交酯）（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）]的L-乳酸共聚物及其在水解降解过程中形成的结晶残留物的水解降解行为。结晶残渣的形成与水解降解 ...更多信息 用凝胶渗透色谱（GPC）和差示扫描量热法（DSC）对产物进行跟踪。获得了以下结果。(1)（2）在pH 7.4时，水解反应的活化能ΔE_h为75.2 kJ mol·L-1<-1>。（<-1>3）酸性、碱性条件和高温均能促进PLLA的水解，而蛋白酶K对PLLA的水解没有催化作用，说明蛋白酶K对PLLA的水解活性不明显。(4)P（LLA-GA）和P（LLA-CL）膜在24周内形成结晶残留物并水解降解，而在PLLA和P（LLA-DLA）（98.8：1.2）膜的情况下，在50周的降解期内既不形成结晶残留物也不水解降解。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