低相对分子质量线型和星形聚乳酸及其共聚物多元醇的合成、结构与性能

利用丙交酯在小分子多元醇链转移剂和辛酸亚锡催化剂的作用下开环聚合或与己内酯共聚,合成了一系列线型和星形聚乳酸和聚(乳酸-co-己内酯)多元醇。获得的聚乳酸和聚(乳酸-co-己内酯)实际相对分子质量接近于理论相对分子质量,且相对分子质量分布较窄。聚合过程研究表明,在多元醇链转移剂下丙交酯开环聚合反应较快,其转化率在10min内达到95%以上,且之后聚乳酸多元醇相对分子质量基本不变。通过差示扫描量热法、热重分析研究了聚乳酸和聚(乳酸-co-己内酯)多元醇的热性能。聚乳酸多元醇的玻璃化转变温度(Tg)随着相对分子质量的增大而升高;己内酯的引入可以有效地降低聚乳酸多元醇的Tg,且提高了聚乳酸多元醇热稳定性。     

利用有机催化剂合成分子量可控聚乳酸

利用有机催化剂--1,8-二氮杂双环[5.4.0]-7-十一碳烯(DBU),以异丙醇为引发剂,实现丙交酯在常温、常压下的活性开环聚合反应,合成可作为医用材料的分子量可控的聚乳酸.反应机理为有机催化剂DBU与引发剂异丙醇通过氢键形成中间体,中间体中呈负电性的氧对丙交酯羰基中的碳进行亲核进攻,使丙交酯单体通过酰氧键断裂,进行开环聚合反应.通过FT-IR和1H NMR对聚乳酸的结构进行了表征.通过调节丙交酯和异丙醇的摩尔比来调控产品聚乳酸的分子量,GPC分析表明该聚合方法能够实现聚乳酸分子量的有效控制,且聚乳酸分子量分布很窄.通过分析聚合反应时间对聚乳酸产率的影响,确定了poly-lactide-3000、polylactide-5000、polylactide-7000 和polylactide-10000的适宜聚合反应时间分别为20、30、40和50min.     

微波辐照合成聚乳酸/氧化锌柱撑有机皂石纳米复合材料及其聚合动力学与结构表征

采用微波水解法制备氧化锌(ZnO)柱撑有机皂石,并以其为催化剂在微波辐照下通过D,L-丙交酯开环聚合制备聚乳酸(PLA)/ZnO柱撑有机皂石纳米复合材料。通过正交实验,获得最优聚合参数,PLA/ZnO柱撑有机皂石纳米复合材料的珨Mw为39322。聚合动力学研究表明该聚合反应为3级反应,表观速率常数为157.264mol-2·L2·s-1。通过X射线衍射、扫描电子显微镜、透射电子显微镜、差示扫描量热分析和热重分析对ZnO柱撑有机皂石、纳米ZnO和PLA/ZnO柱撑有机皂石纳米复合材料的结构进行了表征和分析,结果表明纳米ZnO柱撑有机皂石具有剥离型结构,能显著提高PLA复合材料的结晶性能和热稳定性。     

丙交酯的合成与聚合

丙交酯是由乳酸合成聚乳酸的中间体,采用新型La Ti复合氧化物催化乳酸合成丙交酯,粗丙交酯经乙酸乙酯纯化后,差热分析仪测得其熔点为126 4℃,纯化后的丙交酯在一定条件下,经辛酸亚锡引发,开环聚合成聚乳酸,并用红外光谱和差热分析仪对聚乳酸进行了表征。     

聚乳酸的微波辐射合成方法研究

采用微波加热提供反应所需热量,以丙交酯为原料,辛酸亚锡的甲苯溶液为催化剂,进行丙交酯开环聚合反应,开展了聚乳酸的微波辐射合成工艺及相关基础研究。在最佳条件下(催化剂辛酸亚锡与单体的摩尔比为0.001,SiC作辅助加热介质,微波功率为450W,反应18min)合成了分子量为2.5×104的聚乳酸。     

生物可吸收材料PDLLA的聚合条件研究

通过乳酸脱水合成出高纯度的D ,L 丙交酯。以辛酸亚锡为引发剂 ,进行丙交酯开环聚合为聚乳酸 (PDLLA)的实验研究。讨论了D ,L 丙交酯开环聚合的影响因素和PDLLA聚合条件     

聚乳酸类可生物降解型高分子材料在制备载药微球或微囊中的研究和应用

综述了用聚乳酸(PLA)类可生物降解型高分子材料制备载药微球或微囊的研究背景和现状.重点介绍了包括丙交酯的开环聚合、乳酸直接缩聚制备聚乳酸,丙交酯与乙醇酸开环共聚制备聚乳酸-羟基乙酸共聚物(PLGA),聚乙二醇单甲醚(mPEG)与丙交酯或乳酸开环共聚制备聚乳酸-聚乙二醇(PLA-PEG)嵌段共聚物等3种材料的制备方法;微球的制备方法及其释放机理.阐述了目前应用的主要问题,对发展前景进行了展望.     

聚(天冬氨酸-co-乳酸)的合成及结构与性能

由聚(琥珀酰亚胺-乳酸)的碱溶液水解反应制备了含有亲水性羧基的聚(天冬氨酸-co-乳酸)(PAL)。用IR、NMR、DSC、元素分析等方法表征了PAL的组成和结构。结果表明,PAL中的聚乳酸链段为间同立构或无规立构,由此推断丙交酯在开环聚合反应时发生了酯交换或链转移反应,导致聚乳酸链段产生消旋现象;聚合反应机理是羟基引发的聚合,获得了无定型态聚合物PAL。由于共聚反应中丙交酯熔体的蒸发损耗,合成的PAL中聚天冬氨酸的含量高于理论值。     

钛(IV)配合物催化合成Ti-P聚乳酸材料微观结构分析

以双(烷氧-亚胺芳氧)基钛(IV)配合物为催化剂,催化D,L-丙交酯开环聚合合成Ti-P聚乳酸材料,为分析材料的微观结构和性能,采用IR、1HNMR、13C NMR、TG/DSC、拉伸/压缩以及扫描电镜等方法,对聚乳酸材料进行表征及测试。实验结果表明:该钛(IV)配合物催化D,L-丙交酯的加成反应不是随机加成聚合,存在中等程度的等规加成立构选择性,并能明显阻止分子内的酯交换,对D,L-丙交酯显示出可控开环聚合的特征;与Sn-P聚乳酸相比,采用具有烷氧-亚胺芳氧基大体积空间位阻的钛(IV)配合物为催化剂,可得窄分散度、规整度好的Ti-P聚乳酸,并能提高其热稳定性、抗拉伸和压缩的力学性能。     

聚L-乳酸的制备与性能及在茶碱药物缓释中的应用

以L-乳酸为原料,通过L-丙交酯(LLA)开环聚合制备了聚L-乳酸(PLLA)。采用FT-IR、1 H-NMR对丙交酯及聚乳酸的结构进行了表征。考察了聚合时间对聚乳酸相对分子量的影响,通过TGA、拉力试验机和失重率对聚乳酸薄膜的性能进行了表征,并研究了聚乳酸薄膜在茶碱为模型药物中的控制释放性能。结果表明,当m(LLA)/m(辛酸亚锡)=10000、聚合温度为l40℃,常压聚合20h可制得粘均分子量为8.14×l04的聚乳酸,其薄膜具有较好的热稳定性和力学性能。聚乳酸薄膜在人工胃液中的降解速率随着分子量的增加而降低。茶碱在聚乳酸薄膜中缓释机理为第二类输送机理(近似零级释放机理)。     

微波辐射D,L-丙交酯开环聚合制备聚乳酸

为得到聚乳酸的最佳制备工艺,利用微波辐射技术实现D,L-丙交酯开环聚合制备聚乳酸,实验考查了催化剂种类和用量,微波辐照功率和时间等工艺参数对产物分子量的影响,以及反应过程中体系温度的变化.研究表明,以连续微波炉作为反应器,催化剂Sn(Oct)2用量为丙交酯单体用量的0.56%(质量分数),在功率为90 W的连续微波辐射下反应10 m in,可获得粘均分子量(Mη)为15.92×104的聚乳酸(PDLLA).与家用微波炉相比,采用连续微波炉反应器,可在较短的反应时间内获得较高产率的聚乳酸产物.     

Formation of PLLA-PEG-PLLA Microparticles by Supercritical Antisolvent Process

A biodegradable triblock copolymer of poly(L-lactide)–poly(ethylene glycol)–poly(L-lactide) (PLLA-b-PEG-b-PLLA) was synthesized via a new process by the ring-opening polymerization of L-lactide with PEG as macroinitiator and Sn(Oct)₂ as catalyst. The structure and molecular weight of the polymer were characterized by ¹H NMR spectra, Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography (GPC). Then the microparticles were prepared with the synthesized copolymer by supercritical antisolvent (SAS) process. The optimal operating conditions were explored using an orthogonal array design. The effects of the mixed organic solvent, the concentration of polymer solution and the flow rate of polymer solution on the morphology and thermal properties of the microparticles were investigated experimentally. The morphology, size and thermal properties of microparticles were characterized by scanning electron microscopy (SEM), laser particle size analyzer, x-ray diffractometer (XRD) and differential scanning calorimeter (DSC) respectively. The results indicated that the use of mixed solvent (dichloromethane/acetone) and the polymer concentration played important roles on particle morphology, size and size distribution. In addition the PLLA-PEG-PLLA particles prepared by supercritical antisolvent process have less crystalline.     

Ocular Permeability of Pirenzepine Hydrochloride Enhanced by Methoxy poly(ethylene glycol)–poly(D,L-lactide) Block Copolymer

Methoxy poly(ethylene glycol)–poly(D,L-lactide) block copolymer was tested as an ocular permeation enhancer for pirenzepine hydrochloride. The block copolymers with the methoxy poly(ethylene glycol) to poly(D,L-lactide) weight ratio of 80/20, 50/50, 40/60 were synthesized by a ring-opening polymerization procedure. In vitro transcorneal experiments demonstrated that the block copolymer 80/20 significantly enhanced the transcorneal permeation of pirenzepine at the mass ratio of 1/1.4 (pirenzepine hydrochloride/copolymer). Interaction between pirenzepine and copolymer was identified by infrared spectroscopy analysis and dialysis experiments. Ocular pharmacokinetics of pirenzepine/copolymer preparation by in vivo instillation experiments confirmed that block copolymer could enhance the ocular penetration of pirenzepine. Ocular chronic toxicity experiments of block copolymer and pirenzepine/copolymer preparation were studied on rabbits, and no significant toxicity in both groups was observed within 9 months. It could conclude that pirenzepine/copolymer preparation is effective and safe in ocular delivery of pirenzepine.     

Ocular permeability of pirenzepine hydrochloride enhanced by methoxy poly(ethylene glycol)-poly(D, L-lactide) block copolymer

Methoxy poly(ethylene glycol)-poly(D,L-lactide) block copolymer was tested as an ocular permeation enhancer for pirenzepine hydrochloride. The block copolymers with the methoxy poly(ethylene glycol) to poly(D,L-lactide) weight ratio of 80/20, 50/50, 40/60 were synthesized by a ring-opening polymerization procedure. In vitro transcorneal experiments demonstrated that the block copolymer 80/20 significantly enhanced the transcorneal permeation of pirenzepine at the mass ratio of 1/1.4 (pirenzepine hydrochloride/copolymer). Interaction between pirenzepine and copolymer was identified by infrared spectroscopy analysis and dialysis experiments. Ocular pharmacokinetics of pirenzepine/copolymer preparation by in vivo instillation experiments confirmed that block copolymer could enhance the ocular penetration of pirenzepine. Ocular chronic toxicity experiments of block copolymer and pirenzepine/copolymer preparation were studied on rabbits, and no significant toxicity in both groups was observed within 9 months. It could conclude that pirenzepine/copolymer preparation is effective and safe in ocular delivery of pirenzepine.     

星形聚乙二醇-聚乳酸嵌段共聚物的合成与表征

以不同臂数和分子量的星型聚乙二醇(sPEG)和L-丙交酯为原料,采用开环聚合法合成了以星型聚乙二醇为内部嵌段、聚L-乳酸为外部嵌段的多臂星形聚乙二醇-聚乳酸嵌段共聚物(sPEG-b-PLLA)。研究了sPEG的臂数、分子量及L-丙交酯/sPEG投料比等参数对产物结构与性能的影响。并分别用红外光谱(FT-IR)、核磁共振(1H-NMR)、凝胶渗透色谱(GPC)、差示扫描量热(DSC)对产物进行了表征,证实所合成的嵌段共聚物具有预期的结构。结果表明,sPEG-b-PLLA为结晶性聚合物,且表现出与PLLA相似的晶型,随着PLLA链段的增加,产物的结晶度也呈增大的趋势;与PLLA相比,sPEG-b-PLLA的接触角随着PEG链段的增多而增大,表明其亲水性明显改善。     

壳聚糖-聚乳酸接枝共聚物的制备与表征

以L-乳酸和壳聚糖为原料,辛酸亚锡为催化剂,通过原位聚合法制备了含聚乳酸链段的壳聚糖接枝共聚物,讨论了原料投料比、催化剂浓度对接枝率的影响。通过红外光谱对共聚物化学结构进行分析,并通过热重分析研究其热失重行为。与壳聚糖相比,聚乳酸支链的引入有效削弱了壳聚糖分子的氢键作用,共聚物起始分解温度和热稳定性下降。     

希夫碱钛配合物催化D,L-丙交酯本体开环合成聚乳酸

合成了一种新型双核希夫碱钛配合物,并将此作为催化剂用于D,L型丙交酯本体开环聚合,采用FT-IR、NMR、GPC对合成产物进行表征,研究结果表明该配合物具有催化丙交酯开环较高的催化活性和分子量可控性（PDI=1.09～1.24）。同时进一步研究了该催化剂用量,聚合温度及聚合时间对聚合反应的影响,发现在单体与催化剂摩尔比为2600,聚合时间为16h,聚合温度为160℃时,可得到数均分子质量Mn=9.058×104,PDI=1.16的聚乳酸材料。     

HECS-g-PDLLA共聚物的微波合成及与聚乳酸的相容性

在微波作用下,以辛酸亚锡为催化剂,羟乙基壳聚糖（HECS）为大分子引发剂引发D,L-丙交酯（D,L-LA）开环聚合制备羟乙基壳聚糖-g-聚乳酸（HECS-g-PDLLA）,通过红外（IR）、元素分析（EA）、氢核磁共振（1H-NMR）、X射线衍射（XRD）和差示扫描量热分析（DSC）对产物进行了表征。然后采用溶液共混法...     

The response of macrophages to particles of resorbable polymers and their degradation products

Alpha polyesters such as poly(L-lactide) and poly(glycolide) are biodegradable materials used in fracture fixation and they need to be assessed for problems associated with their degradation products. This study has compared cell responses to low molecular weight poly(L-lactide) particles, lactate monomer, poly(glycolide) particles and glycolic acid at cytotoxic and sub-cytotoxic concentrations. Murine macrophages were cultured in vitro and the release of lactate dehydrogenase (LDH), prostaglandin E₂ (PGE₂ and interleukin-1 alpha IL-1 was measured following the addition of particles or monomer. Experiments revealed that both the poly(L-lactide) and poly(glycolide) particles gave rise to dose dependent increases in LDH release and an increase in IL-1 and PGE₂ release. Comparisons of the poly(L-lactide) particles to the poly(glycolide) particles did not reveal any differences in their stimulation of LDH, IL-1 and PGE₂ release. The lactate and glycolate monomers did not increase PGE₂ or IL-1 release above control levels. There was no difference in biocompatibility between the poly(L-lactide) and poly(glycolide) degradation products both in particulate and monomeric form.     

Synthesis and characterization of polyurethane-grafted single-walled carbon nanotubes via click chemistry

Polyurethane (PU)-grafted carbon nanotubes were synthesized by the coupling of alkyne moiety decorated single walled carbon nanotube (SWCNT) with azide moiety containing PU using Cu(I) catalyzed Huisgen [3 + 2] cycloaddition click chemistry. The azide moiety containing poly(s-caprolactone)diol was synthesized by ring-opening polymerization and further used for PU synthesis. Alkyne-functionalizion of SWCNT was completed by the reaction of p-aminophenyl propargyl ether with SWCNT using a solvent free diazotization procedure. Nuclear magnetic resonance, Fourier transform infrared, and Raman spectroscopic measurements confirmed the functionalization of SWCNT. Scanning electron microscopy and transmission electron microscopy images showed an excellent dispersion of SWCNTs, and specially debundling of SWCNTs could be observed due to polymer assisted dispersion. A quantitative grafting was successfully achieved even at high content of functional groups.