三亚甲基环碳酸酯及2,2-二甲基三亚甲基环碳酸酯开环均聚合*

生物降解聚合物聚三亚甲基环碳酸酯（PTMC）及聚2,2-二甲基三亚甲基环碳酸酯（PDTC）在药物控释载体及其它生物医学技术领域有着良好的应用前景。与脂肪族聚酯不同,PTMC、PDTC降解时,不会产生有害的酸性化合物。PTMC、PDTC主要由三亚甲基环碳酸酯（TMC）及2,2-二甲基三亚甲基环碳酸酯（DTC）开环均聚合制备。本文总结了催化TMC、DTC开环均聚合的不同催化剂及其聚合机理,综述了近年来国内外在TMC、DTC均聚合催化剂开发上的研究进展,并对生物相容性催化剂如稀土催化剂、Ca、Mg、Zn、Fe催化剂以及酶催化剂催化TMC、DTC开环聚合的优缺点进行了比较。     

三(2,6-二叔丁基-4-甲基-苯氧基)镧催化ε-己内酯低温聚合特征及与环碳酸酯嵌段共聚

摘要用三(2,6-二叔丁基-4-甲基-苯氧基)镧[La(OAr)₃]在-15 ℃引发ε-己内酯(CL)的开环聚合, 发现聚合体系具有活性聚合特征. 在第二步聚合过程中继续补加第二种单体三亚甲基环碳酸酯(TMC)或二甲基三亚甲基环碳酸酯(DTC), 可得到CL与环碳酸酯的嵌段共聚物.     

聚三亚甲基碳酸酯的研究进展

聚三亚甲基碳酸酯具有良好的生物降解性能及生物相容性,是一种重要的生物降解医用高分子材料,在生物医用领域具有较大的应用前景。本文结合近年来的研究进展,综述了阳离子开环聚合、阴离子开环聚合、配位聚合、酶促开环聚合以及微波开环聚合等方法在聚三亚甲基碳酸酯制备过程中的应用,总结了聚三亚甲基碳酸酯的分子量与物理性能的关系,并重点讨论了聚三亚甲基碳酸酯的体内外降解性能,详细描述了分子量及脂肪酶对聚三亚甲基碳酸酯降解行为的影响,最后总结了聚三亚甲基碳酸酯在生物医用领域的应用。     

聚三亚甲基碳酸酯的生物相容性研究

以实验室自制的聚三亚甲基碳酸酯(PTMC)为研究对象,通过测定聚三亚甲基碳酸酯在体外酶解过程中降解液pH变化,考察其在降解过程中是否产生酸性降解产物;通过MTS法考察聚三亚甲基碳酸酯的体外细胞毒性;通过HE染色的方法考察聚三亚甲基碳酸酯在大鼠体内埋植部位的皮肤刺激性,进而考察聚三亚甲基碳酸酯的生物相容性。结果表明:PTMC在降解过程中不产生酸性降解产物,可避免埋植部位无菌炎症的产生。同时不同分子量的PTMC可以存在于皮下组织而不会造成伤害,因此聚三亚甲基碳酸酯具有良好的生物相容性,可安全植入体内。     

苄醇存在下脂肪叔胺催化内酯开环聚合

为研究脂肪叔胺结构对内酯开环聚合规律的影响,以三乙胺( TEA)、N,N,N′,N′-四甲基乙二胺(TMEDA)、N,N,N′,N″,N″-五甲基二亚乙基三胺(PM DTA)3种不同结构的叔胺催化碳酸三亚甲基酯(TMC)和左旋丙交酯( L-LA)开环聚合.结果显示,在55℃的THF溶液中,以苄醇为引发剂,3种叔胺均能催...     

大环碳酸酯的Novozym-435酶促开环聚合

研究了14元环的碳酸丁二酯二聚体在固定化脂肪酶Novozym-435催化下的开环聚合反应制备聚碳酸丁二酯.聚合在常压,75℃的甲苯溶液中进行,反应条件温和.详细探讨了反应条件诸如单体浓度,酶浓度对于聚合的影响.结果显示Novozym-435具有与异辛酸亚锡可比拟的高催化活性,同时可以回收重复使用.聚合动力学研究表明碳酸丁二酯的酶促甲苯溶液开环聚合和环状内酯的酶促甲苯溶液聚合有所不同,没有表现出活性聚合的特征.     

立构复合PL(D) LA-TMC无规共聚物的制备、结构与性能

以辛酸亚锡为催化剂,通过开环聚合法制备了聚左旋乳酸-三亚甲基碳酸酯(PLLA-TMC)和聚右旋乳酸-三亚甲基碳酸酯(PDLA-TMC)无规共聚物.利用共聚物中PLLA/PDLA链段形成立构复合体,通过溶液浇注法制备了PLLA-TMC/PDLA-TMC立构复合聚乳酸材料(sc-PLA-TMC).研究结果表明,聚合物链中的柔性TMC单元可以增强L(D)LA链段的运动能力,有助于不同旋光性的LA链段形成立构复合晶体,但也使得L(D)LA链段的规整度和序列长度降低.即随着共聚物链段中柔性TMC单元摩尔含量的增加,sc-PLA-TMC中同质结晶能力降低.当TMC含量≥5%时,仅生成熔点200℃的PLLA/PDLA立构复合结晶,表明sc-PLA-TMC的耐热性有所提高.蛋白酶K降解实验表明,PL(D)LA-TMC共聚物的降解速率不但比PLLA高,而且可通过共聚物中TMC含量进行调控.     

天然氨基酸作用下2,2-二甲基三亚甲基碳酸酯的开环聚合

研究了几种中性天然氨基酸存在下2,2-二甲基-三亚甲基环碳酸酯(DTC)的开环聚合反应。1H-NMR和端基滴定分析表明,在聚合反应过程中,DTC上的酰氧键断裂,氨基酸通过氨基接在聚(2,2-二甲基-三亚甲基碳酸酯)链上。3-氨基丙酸、4-氨基丁酸、6-氨基己酸等存在时,DTC的聚合反应也可以发生,但单体的转化率和聚合物的分子量低于天然氨基酸引发的聚合反应。     

PNIPAM-b-聚碳酸酯温敏胶束的制备及用作药物控制释放载体的研究

以多孔硅球固定化猪胰脂肪酶(IPPL)为催化剂,温敏性HO-PNIPAM为大分子引发剂,5-甲基-5-烯丙氧羰基-三亚甲基碳酸酯(MAC)和5,5-二甲基三亚甲基碳酸酯(DTC)为共聚单体,通过开环聚合合成了不同结构比例的两亲性嵌段型共聚物P(MAC-co-DTC) -b-PNIPAM.该嵌段型共聚物在水中可自组装形成...     

生物可降解封堵器材料的合成及表征

以L型丙交酯(LLA)、乙交酯(GA)和三亚甲基碳酸酯(TMC)为原料,辛酸亚锡为催化剂,通过开环聚合制备了丙交酯-三亚甲基碳酸酯二元共聚物(PLT)和丙交酯-三亚甲基碳酸酯-乙交脂(PLTG)三元共聚物。采用核磁共振氢谱、傅里叶红外光谱、体积排阻色谱、差热扫描、力学性能测试、血液相容性实验表征了产物的结构与性能,研究了共聚物组成对其结晶能力、热性能和力学性能的的影响。结果表明:所得聚合物的数均分子量均在8×10~4以上,多分散系数在2.0以下。共聚物中的TMC和GA链段使其结晶能力、玻璃化转变温度和拉伸强度与L型聚丙交酯相比均有所下降。三元共聚物PLTG的拉伸强度可达到22.3 MPa,断裂伸长率达到168.7%。另外,共聚物的血液相容性优良。     

Enzymatic ring-opening polymerization of 2,2-dimethyltrimethylene carbonate catalyzed by PPL immobilized on silica nanoparticles

Silica nanoparticles were first used as the carrier for the porcine pancreas lipase (PPL) immobilization. The result of transmission electron microscopy (TEM) showed that the immobilized lipase was still in nanosize after enzyme immobilization. The ring-opening polymerization of 2,2-dimethyltrimethylene carbonate (DTC) catalyzed by this immobilized PPL (IMPPL) was explored. ¹H NMR spectra suggested no evidence of decarboxylation during propagation. Influences of IMPPL concentration and reaction temperature on the molecular weight and yield of poly(DTC) were studied. The recovery and reuse of IMPPL for the ring-opening polymerization of DTC was also investigated. The recycling IMPPL showed even higher catalytic activity and a higher molecular weight of polycarbonate could be achieved.     

Rapid synthesis of poly(trimethylene carbonate) by microwave-assisted ring-opening polymerization

Poly(trimethylene carbonate) (PTMC) was synthesized successfully by microwave-assisted ring-opening polymerization of trimethylene carbonate. The polymerizations were carried out in a single-mode microwave oven using ethylene glycol (EG) as the initiator in the absence of any metallic compound catalyst. The temperature-time profiles of the reaction mixture were investigated at different power levels and EG concentrations. The molar mass of the resulting PTMC and TMC monomer conversion by the microwave method is higher than those by the conventional method. Thermal properties of the resulting polymers were studied by differential scanning calorimetry. Microwave irradiation proved to be an effective and efficient method for the preparation of PTMC.     

RING-OPENING POLYMERIZATION OF TRIMETHYLENE CARBONATE CATALYZED BY NOVEL SINGLE COMPONENT RARE EARTH CALIXARENE COMPLEXES

In this paper, ring-opening polymerization of trimethylene carbonate (TMC) with rare earth (Nd, Y, La) p-tert-butylcalix[n]arene (n=4, 6, and 8) complexes as catalysts has been studied. Poly(trimethylene carbonate) (PTMC) with Mv of 21,400 was produced by bulk polymerization under the conditions as follows: [TMC]0/[Nd] (molar ratio)=1000,80℃,8h. Mechanism study reveals that the polymerization proceeds via a coordination mechanism.     

聚ε-己内酯的微米硅球固定化猪胰脂肪酶促合成

本文采用微米硅球固定化猪胰脂肪酶为催化剂合成聚ε-己内酯, 以期获得具有较高分子量、 良好生物相容性和使用安全性的生物可降解医用高分子材料.     

Hydrolytic and enzymatic degradation of poly(trimethylene carbonate-co-d,l-lactide) random copolymers with shape memory behavior

A series of homo- and copolymers were synthesized by ring-opening polymerization of 1,3-trimethylene carbonate and d,l-lactide, using low toxic Zn(Lac)₂ as catalyst. The hydrolytic and enzymatic degradation of PTMC homopolymer and PTDLA copolymers was performed at 37 °C in pH 7.4 phosphate buffered saline or in pH 8.5 Tris buffer using proteinase K. Degradation was followed by using various analytical techniques such as NMR, GPC, DSC and ESEM. PTMC degrades extremely slowly by pure hydrolysis or in the presence of proteinase K. In contrast, PTDLA copolymers with different compositions degrade at various rates both in PBS and in enzyme solutions. The higher the LA content, the faster the degradation. LA units are preferentially degraded during hydrolytic degradation, indicating that ester bonds are more susceptible to hydrolytic cleavage than carbonate ones. Changes in surface morphology are observed during enzymatic degradation, in agreement with surface erosion process. The PTDLA11 copolymer with equivalent TMC/LA contents is highly elastic. Its residual strain is approximately 4% after the first cycle at a strain of 50%. The shape recovery ratio is up to 83%. Therefore, it is concluded that high molecular weight PTDLA copolymers are promising candidates for clinical applications in minimally invasive surgery.     

Synthesis and chemical recycling of novel poly(ester-urethane)s using an enzyme

A series of enzymatically recyclable poly(ester-urethane)s consisting of a biodegradable diurethane moiety as a hard segment and an ester moiety as an enzymatically cleavable linkage was chemo-enzymatically prepared by two routes. The poly(ester-urethane) was prepared by a) the ring-opening polymerization of a cyclic ester-urethane monomer synthesized via the transesterification reaction of biodegradable diurethanediol and dicarboxylate ester using lipase and b) the direct polycondensation of a diurethanediol and a dicarboxylate ester. A significantly higher molecular-weight poly(ester-urethane) having the highest molecular weight (Mw) of 101,000 was produced by the ring-opening polymerization of the cyclic ester-urethane monomer when compared with that produced by the polycondensation of the dicarboxylate ester with diurethanediol. The poly(ester-urethane) was readily degraded by lipase into the corresponding cyclic oligomers; the oligomers were readily repolymerized by the ring-opening polymerization using lipase for chemical recycling.     

Y‐shaped poly(ethylene glycol) and poly(trimethylene carbonate) amphiphilic copolymer: Synthesis and for drug delivery

New Y‐shaped (AB₂‐type) amphiphilic copolymers of poly(ethylene glycol) (PEG) with poly(trimethylene carbonate) (PTMC), PEG‐b‐(PTMC)₂, were successfully synthesized by the ring‐opening polymerization (ROP) of TMC with bishydroxy‐modified monomethoxy‐PEG (mPEG). First, a bishydroxy functional ROP initiator was synthesized by esterification of acryloyl bromide with mPEG, followed by Michael addition using excess diethanolamine. A series of Y‐shaped amphiphilic PEG‐(PTMC)₂ block copolymers were obtained via ROP of TMC using this PEG with bishydroxyl end groups as macroinitiator and ZnEt₂ as catalyst. The amphiphilic block copolymers with different compositions were characterized by gel permeation chromatography (GPC) and ¹H NMR, and their molecular weight was measured by GPC. The results showed that the molecular weight of Y‐shaped copolymers increased with the increase of the molar ratio of TMC to mPEG‐(OH)₂ initiator in feed while the PEG chain length was kept constant. The Y‐shaped copolymer mPEG‐(PTMC)₂ could self‐assemble into micelles in aqueous medium and the critical micelle concentration values of the micelles decrease with increase in hydrophobic PTMC block length of mPEG‐(PTMC)₂. The in vitro cytotoxicity and controlled drug release properties of the Y‐shaped amphiphilic block copolymers were also investigated. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 8131–8140, 2008     

Synthesis of functional polycarbonates by lipase-catalyzed ring-opening polymerization

Poly(5-benzyloxy-trimethylene carbonate) (PBTMC), a new functional polycarbonate was synthesized by enzymatic ring-opening polymerization in bulk at 150°C using Porcine pancreas lipase (PPL) or Candida rugosa lipase (CL) as catalyst. Influences of different polymerization conditions such as the source of enzyme, enzyme concentration and polymerization time on the molecular weight and yield were studied. The results showed that PPL exhibited higher activity than CL. Both higher molecular weight(Mn, 18953) and yield(98%) could be obtained by the use of PPL as catalyst. ¹H NMR spectrum showed no decarboxylation occurrence during the ring-opening polymerization.     

Use of samarium (III) acetate as initiator in ring-opening polymerization of trimethylene carbonate

Abstract

In this work was evaluated the activity of samarium acetate (III) (Sm(OAc)₃) as a possible initiator in the polymerization by ring opening of trimethylene carbonate (TMC). All polymerizations were carried out under solvent-free melt conditions in ampoules-like flasks, equipped with a magnetic stirrer. The effects of different parameters of reaction, such as molar ratio monomer to initiator, temperature and reaction time, on typical variables of polymers, e.g., conversion of TMC to poly(trimethylene carbonate) (PTMC), dispersity and molar mass, were analyzed. The molar ratio of monomer to initiator was varied between 0 and 1000?mol/mol and the temperature among 70 and 150?°C. Nuclear Magnetic Resonance (¹H-NMR and HMBC) and Size Exclusion Chromatography (SEC) were used to characterize the polymers. The results indicate that the Sm(OAc)₃ induces the polymerization of TMC to high conversion with number-average molecular weights of 3.11?×?10³ to 38.40?×?10³?Da. Based on the ¹H-NMR end-group analysis of low-molecular-weight PTMC, it was proposed a coordination–insertion mechanism for the polymerization, with a breakdown of the acyl-oxygen bond of the TMC. In according to the kinetic study carried out, the polymerization rate is first-order with respect to monomer concentration with apparent rate constants of k_ap?=?7.02?×?10^?4?mol?×?L^?1?×?h^?1.