乳酸—乙醇酸共聚物合成及其扩链反应研究
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摘要
以L-乳酸(L-LA)和乙醇酸(GA)为原料通过直接熔融缩聚制备聚(L-乳酸乙醇酸)(PLGA),并将其分别与扩链剂4,4-二苯基甲烷二异氰酸酯(MDI)和1,6-亚己基二异氰酸酯(HDI)进行熔融扩链反应,以进一步提高PLGA的分子量。采用粘度测试法、端基滴定法、激光光散射法对共聚物的分子量进行表征,采用红外光谱(IR)、核磁共振(H1NMR)、差示量热扫描仪(DSC)和热稳定性测试仪(TGA)对扩链反应前后聚合物的结构与性能进行研究。
结果表明,采用MDI和HDI为扩链剂时,均在相同的熔融扩链条件下(扩链时间为20 min,扩链温度为160℃,-NCO:-OH=4:1),得到的PLGA具有最高的特性粘数,且分别为扩链前的2.05倍和2.82倍;通过端基滴定法测定共聚物的数均分子量可达50000,而通过激光光散射法测得共聚物的重均分子量可达51300。
以不同摩尔比的L-乳酸(L-LA)和乙醇酸(GA)为原料制备的聚(L-乳酸-乙醇酸)(PLGA)与扩链剂4,4-二苯基甲烷二异氰酸酯(MDI)进行熔融扩链反应后,则发现, L-乳酸所占摩尔比的增加有利于扩链反应的发生。
红外光谱测试表明,聚合物在熔融共聚阶段有酯键形成,并在扩链过程中与异氰酸酯键发生反应;核磁共振谱表明,GA在PLGA共聚物中的组成比大于投料时组成比,说明在反应过程中,GA的反应活性大于LA;差式扫描量热仪测试结构表明,PLGA的玻璃化转变温度随着GA含量的增多而增加,且扩链后聚合物的玻璃化转变温度高于扩链前;热稳定性测试仪(TGA)测试结果表明,随着GA的增加,PLGA的热稳定性增加且扩链后聚合物的热稳定性高于扩链前。
In this thesis, the PLGA were synthesized via direct melt co-polycondensation, by using L-lactic acid (L-LA) and glycolic acid (GA) as staring materials. At the same time, the 4,4-diphenylmethane diisocyanate (MDI) or hexamethylene diisocyanate (HDI) was used as a chain extension agent to increase the molecular weight of polymer, which the chain extension reaction of PLGA was carried out in melt state. The molecular weight of copolymers were identified through viscosity test, end-group titration and laser light scattering method. Reference to the structure and properties of polymers, which was characterized with FT-IR, 1H-NMR, DSC and TGA.
The results indicated that, the intrinsic viscosity ([η]) of PLGA was doubled or more (2.05 and 2.82 times, respectively) in the same condition (-NCO/-OH=4∶1 (mol ratio); time: 20min; temperature: 160℃) when used MDI or HDI as chain extension agent. In addition, at the same condition, a number-average molecular weight by end-group titration copolymer is up to of 50,000, and by laser light scattering method the weight average molacular weigth of copolymer could reach 51300.
It also can be found that, the PLGA which was using L-lactic acid (L-LA) and glycolic acid (GA) as staring materials, and synthesized via direct melt co-polycondensation with different molar feed ratio, in the chain extension reacted with 4,4-diphenylmethane diisocyanate (MDI) which was as a chain extension agent, the probability of the reaction of chain extension was enhanced with increased of the molar feed ratio of LA.
IR spectra showed that the polymer ester bond is formed in the melt copolymerization stage, and isocyanate bond come into being in the process of chain expanding reaction. The result of 1H-NMR spectra showed that, the ratio of GA composition in PLGA copolymer is more than the feed ratio, which means in the reaction process, the reactivity of GA is greater than LA. Differential scanning calorimeter test structure indicated that, with the increase of GA content, the glass transition temperature of PLGA heightened, and the glass transition temperature of the the chain extended copolymer is higher than the former. Thermal stability test instrument (TGA) test results showed that, with the GA increased, the thermal stability of PLGA could be higher, even better than the one before the chain extended reaction.
结果表明,采用MDI和HDI为扩链剂时,均在相同的熔融扩链条件下(扩链时间为20 min,扩链温度为160℃,-NCO:-OH=4:1),得到的PLGA具有最高的特性粘数,且分别为扩链前的2.05倍和2.82倍;通过端基滴定法测定共聚物的数均分子量可达50000,而通过激光光散射法测得共聚物的重均分子量可达51300。
以不同摩尔比的L-乳酸(L-LA)和乙醇酸(GA)为原料制备的聚(L-乳酸-乙醇酸)(PLGA)与扩链剂4,4-二苯基甲烷二异氰酸酯(MDI)进行熔融扩链反应后,则发现, L-乳酸所占摩尔比的增加有利于扩链反应的发生。
红外光谱测试表明,聚合物在熔融共聚阶段有酯键形成,并在扩链过程中与异氰酸酯键发生反应;核磁共振谱表明,GA在PLGA共聚物中的组成比大于投料时组成比,说明在反应过程中,GA的反应活性大于LA;差式扫描量热仪测试结构表明,PLGA的玻璃化转变温度随着GA含量的增多而增加,且扩链后聚合物的玻璃化转变温度高于扩链前;热稳定性测试仪(TGA)测试结果表明,随着GA的增加,PLGA的热稳定性增加且扩链后聚合物的热稳定性高于扩链前。
In this thesis, the PLGA were synthesized via direct melt co-polycondensation, by using L-lactic acid (L-LA) and glycolic acid (GA) as staring materials. At the same time, the 4,4-diphenylmethane diisocyanate (MDI) or hexamethylene diisocyanate (HDI) was used as a chain extension agent to increase the molecular weight of polymer, which the chain extension reaction of PLGA was carried out in melt state. The molecular weight of copolymers were identified through viscosity test, end-group titration and laser light scattering method. Reference to the structure and properties of polymers, which was characterized with FT-IR, 1H-NMR, DSC and TGA.
The results indicated that, the intrinsic viscosity ([η]) of PLGA was doubled or more (2.05 and 2.82 times, respectively) in the same condition (-NCO/-OH=4∶1 (mol ratio); time: 20min; temperature: 160℃) when used MDI or HDI as chain extension agent. In addition, at the same condition, a number-average molecular weight by end-group titration copolymer is up to of 50,000, and by laser light scattering method the weight average molacular weigth of copolymer could reach 51300.
It also can be found that, the PLGA which was using L-lactic acid (L-LA) and glycolic acid (GA) as staring materials, and synthesized via direct melt co-polycondensation with different molar feed ratio, in the chain extension reacted with 4,4-diphenylmethane diisocyanate (MDI) which was as a chain extension agent, the probability of the reaction of chain extension was enhanced with increased of the molar feed ratio of LA.
IR spectra showed that the polymer ester bond is formed in the melt copolymerization stage, and isocyanate bond come into being in the process of chain expanding reaction. The result of 1H-NMR spectra showed that, the ratio of GA composition in PLGA copolymer is more than the feed ratio, which means in the reaction process, the reactivity of GA is greater than LA. Differential scanning calorimeter test structure indicated that, with the increase of GA content, the glass transition temperature of PLGA heightened, and the glass transition temperature of the the chain extended copolymer is higher than the former. Thermal stability test instrument (TGA) test results showed that, with the GA increased, the thermal stability of PLGA could be higher, even better than the one before the chain extended reaction.
引文
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[5]赵京波,杨万泰,合成生物降解性聚酯研究的进展[J].高分子通报, 1999, (2); 11-19
[6]贺爱军.降解塑料的开发进展[J].化工新型材料, 2002, 30(3): 1-6
[7]方少明,门春绵等.生物及光降解高分子材料的研究开发动向[J].材料导报,1998,12 (1):51-53
[8]王身国.可生物降解的高分子类型、合成和应用[J].化学通报.1997, (2): 45-46
[9]戈进杰.生物降解高分子材料及其应用[M].北京化学工业出版社,2002:392-402
[10]刘伟雄.乳酸和聚乳酸的最新进展[J].食品与发酵工业,2000,27(3):61-65
[11] Dong C M,Qiu K Y,Gu Z W,et a1.Synthesis of star-shaped poly(D,L-lactic acid- alt- glycolic acid)- b- poly(L-lactic acid)with the poly(D,L- lactic acid- alt- glycolic acid) macroinitiator and slan/lous octoate catalystl[J].Journal of Polymer Science,Part A:Polymer Chemistry,2002,40 (3):409-415.
[12]汪朝阳,赵耀明.聚乙醇酸类生物降解高分子[J].广州化学.2004,29(1):50-57
[13]汪朝阳,赵耀明,王方.熔融共聚法用外消旋乳酸直接合成聚乙醇酸-乳酸及其表征[J].现代化工.2004,24 (10):28-30.
[14] Gao Q w,lan P,Shao H L,et a1.Direct synthesis with meltpolycondensation and micro-structure analysis of poly(L-lactic acid-co-glycolic acid) [J].Polymer Journal, 2002, 34(11):786-793.
[15]张倩,虞鑫.交替共聚聚乙丙交酯的合成及表征[J].塑料工业, 2003, 31(5):5-6
[16]汪朝阳,赵耀明,王方等.生物降解材料PLGA50的直接法合成与表征[J].化学推47进剂与高分子材料. 2004, 2 (5):35-38.
[17]李洪权,全大萍,廖凯荣.聚乳酸类生物可降解塑料概论[J].化工新型材料.1992.7. (8):3-6
[18] Wang Y,Challa P,Epstein D L,et a1.Controled release of ethacrynic acid from poly(1actide-co-glycolde) films for aucomatreatment [J]. Biomaterials,2004,25(18): 4279-4285.
[19] Xue J M, Shi M. PLGMmeseporous silica hybrid structLrefor controled drug release [J]. Journal of Controled Release, 2004, 98(2): 209-217.
[20]卢凌彬,黄可龙.可生物降解聚丙交酯乙交酯微粒制备技术的研究进展[J].化工进展,2004,23(1):38-43.
[21]胡云霞,常津,郭毅,等.PLGMO—CMC载药纳米粒子的体外释药行为研究[J].高分子通报,2004,(5):62-68.
[22] Woo S, Kim B O,Jun H S, et al Polymerization of Aqueous Lactic Acid to Prepare High Molecular Weight Poly( lactic acid) by Chain-extending with Hexamethylene Diisocyanate [J]. Polym Bull 1995. 35(4): 415-421
[23]钟伟,戈进杰,马敬红,等.聚乳酸的直接缩聚制备及其异氰酸酯扩链探索[J].复旦学报(自然科学版), 1999, 38 ( 6): 705-708
[24] Tuominen J. Synthesis and Characterization of Lactic Acid Based Poly( ester 2 amide) [ J]. Macromolecules, 2000, 33 (10): 3530-3535.
[25] Kymae J, Heminen A, et al. Chain Extending of Lactic Acid O ligomers Effect of 2, 2 Primebis (22oxazoline) on 1, 6-Hexamethylene Diisocyanate Linking Reaction [J].Polymer, 2001, 42 (8):3333-3343.
[26] Bikiaris D N, Karayarmidis G P, Chain extension of polyesters PET an d PBT with two new diimidodiepo aides[J]. Journal of Polymer Science, Part A: Polymer Chemistry, 1996, 34(7): 1337-1342
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