三亚甲基碳酸酯—丙交酯共聚物的合成、表征及其药物控制释放系统的研究
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摘要
生物可降解高分子材料是生物医用材料的重要组成部分。聚丙交酯由于具有良好的生物相容性、力学性能、无毒以及无免疫原性而广泛的应用在缝合线、药物控释系统和组织工程支架等方面。近年来由于生物可降解脂肪族聚碳酸酯的一些优良的性能已成为研究的热点。脂肪族聚碳酸酯多采用一些低毒性的金属化合物如辛酸亚锡、异丙醇铝等催化开环聚合来制备。生物可降解脂肪族聚碳酸酯、聚酯及其共聚物方面研究的深入会使其在手术缝合线、骨固定材料以及药物控释等生物医用领域有更加广阔应用前景。
合成两种单体的无规共聚物是改善各自均聚物性能的一种有效方法,本文先合成了三亚甲基碳酸酯(TMC)和D,L-丙交酯(D,L-LA),并选用辛酸亚锡做为合成生物可降解高分子的催化剂,合成了聚三亚甲基碳酸酯和聚丙交酯;用无规共聚的方法,合成了共聚组成为75/25、50/50、25/75的聚三亚甲基碳酸酯-D,L-丙交酯的共聚物,通过~1H NMR谱、GPC、DSC和体外降解试验等试验方法对均聚物及共聚物的分子量、分子量分布、热行为和降解性能等进行表征。
以O/W溶剂挥发法制备了微球,考察了其体外降解行为,以左旋炔诺酮为模型药物,O/W溶剂挥发法制备了载药微球,考察均聚物和用不同组成比聚三亚甲基碳酸酯-D,L-丙交酯制备的载药微球的药物释放行为,体外试验表明LNG从由PTMC制备的载药微球中以比较近似恒速的速率释放出来。五种载药微球的LNG释放均无突释效应,释放周期基本相同,组成比的不同对控制释放的影响不大。聚丙交酯的药物释放速度波动较大,偏离恒速释放很多,另外聚丙交酯的释放速度较其他组成的材料快。
Biodegradable polymer is a very important part of biomedical materials.Polylactide has been widely used in medical applications,such as surgical sutures、bone-fixed materials、drug controlled release、scaffold,and so on,for its excellent mechanical property、good biocompatibility and low toxicity.In recent years,biodegradable polycarbonate became one of the most attractive biomedical materials for its some good properties.Biodegradable polycarbonate、Polyester and their copolymer are promising to be used in the biomedical fields.This article focused on the TMC、LA and their polymerization.
To improve the properties of homopolymers,it's a good method that to synthsis block copolymer or random copolymer,by using different feed composition.Firstly,the monomers,Trimethylene carbonate and D,L-Lactide,were synthesized and purified with the modified methods of literature.Copolymers and homopolymers were synthesized via ring-opening polymerization.Sn(Oct)_2 has been chosen to start the homopolymerization of TMC and D,L-LA and their random copolymerization.PTMC、PDLLA and PTMC-co-LA were obtained with Sn(Oct)_2 as catalyst at high yield.
Secondary,Polymers were to be characterized.The feed compositions of copolymers were 75/25、50/50 and 25/75.The actual compositions of the copolymers were measured by ~1HNMR.The results showed that the feed compositions were near the compositions of copolymers.The properties of the copolymers and homopolymers were assayed by DSC、GPC、Degradation in vitro.
Finally,the model drug release behavior and degradation behavior of systems based on the mentioned above copolymers and homopolymers were investigated.The microballoon loading Levonorgestrel were prepared by O/W solvent evaporation method.The microballons immersed in 15%(V/V)ethanol/water mixsolvent were put into incubater at 37℃.The immersion solvent was refreshed regularly and its absorbance at 248nm on UV spectra was recorded.The results showed that the burst effect of all the microballoons was very low,To som extent The LNG release rate was related with the compositions of copolymers.The degradation rates of all the microballoons are rather slow.
合成两种单体的无规共聚物是改善各自均聚物性能的一种有效方法,本文先合成了三亚甲基碳酸酯(TMC)和D,L-丙交酯(D,L-LA),并选用辛酸亚锡做为合成生物可降解高分子的催化剂,合成了聚三亚甲基碳酸酯和聚丙交酯;用无规共聚的方法,合成了共聚组成为75/25、50/50、25/75的聚三亚甲基碳酸酯-D,L-丙交酯的共聚物,通过~1H NMR谱、GPC、DSC和体外降解试验等试验方法对均聚物及共聚物的分子量、分子量分布、热行为和降解性能等进行表征。
以O/W溶剂挥发法制备了微球,考察了其体外降解行为,以左旋炔诺酮为模型药物,O/W溶剂挥发法制备了载药微球,考察均聚物和用不同组成比聚三亚甲基碳酸酯-D,L-丙交酯制备的载药微球的药物释放行为,体外试验表明LNG从由PTMC制备的载药微球中以比较近似恒速的速率释放出来。五种载药微球的LNG释放均无突释效应,释放周期基本相同,组成比的不同对控制释放的影响不大。聚丙交酯的药物释放速度波动较大,偏离恒速释放很多,另外聚丙交酯的释放速度较其他组成的材料快。
Biodegradable polymer is a very important part of biomedical materials.Polylactide has been widely used in medical applications,such as surgical sutures、bone-fixed materials、drug controlled release、scaffold,and so on,for its excellent mechanical property、good biocompatibility and low toxicity.In recent years,biodegradable polycarbonate became one of the most attractive biomedical materials for its some good properties.Biodegradable polycarbonate、Polyester and their copolymer are promising to be used in the biomedical fields.This article focused on the TMC、LA and their polymerization.
To improve the properties of homopolymers,it's a good method that to synthsis block copolymer or random copolymer,by using different feed composition.Firstly,the monomers,Trimethylene carbonate and D,L-Lactide,were synthesized and purified with the modified methods of literature.Copolymers and homopolymers were synthesized via ring-opening polymerization.Sn(Oct)_2 has been chosen to start the homopolymerization of TMC and D,L-LA and their random copolymerization.PTMC、PDLLA and PTMC-co-LA were obtained with Sn(Oct)_2 as catalyst at high yield.
Secondary,Polymers were to be characterized.The feed compositions of copolymers were 75/25、50/50 and 25/75.The actual compositions of the copolymers were measured by ~1HNMR.The results showed that the feed compositions were near the compositions of copolymers.The properties of the copolymers and homopolymers were assayed by DSC、GPC、Degradation in vitro.
Finally,the model drug release behavior and degradation behavior of systems based on the mentioned above copolymers and homopolymers were investigated.The microballoon loading Levonorgestrel were prepared by O/W solvent evaporation method.The microballons immersed in 15%(V/V)ethanol/water mixsolvent were put into incubater at 37℃.The immersion solvent was refreshed regularly and its absorbance at 248nm on UV spectra was recorded.The results showed that the burst effect of all the microballoons was very low,To som extent The LNG release rate was related with the compositions of copolymers.The degradation rates of all the microballoons are rather slow.
引文
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