吗啉二酮衍生物与L-丙交酯共聚物的体外降解性能

研究了37℃下吗啉二酮衍生物与L-丙交酯的共聚物在磷酸盐缓冲液(PBS)中的降解,并且与聚(L-丙交酯与乙交酯)(PLGA)的降解进行了比较。通过静滴接触角测量、扫描电镜(SEM)、X衍射(XRD)、凝胶色谱仪(GPC)、核磁共振(1H-NMR)和红外光谱(FT-IR)等方法研究了材料的亲水性、表面形貌、结晶结构、失重率、分子量和结构的变化等。结果表明:与PLGA相比,吗啉二酮衍生物与L-丙交酯的共聚物具有更好的亲水性,接触角达到了74°,降解3个月后数均分子量下降80%以上,该共聚物能够实现两组份的同步降解。     

聚dl-丙交酯/羟基磷灰石复合材料Ⅲ.体内外降解性能研究

研究了聚dl 丙交酯 /羟基磷灰石复合材料在体内外降解中力学强度、分子量、重量及微观形貌的变化。体内降解是将聚dl 丙交酯 /羟基磷灰石 (40mm× 3mm× 2mm)植入兔子皮下软组织内 ;体外降解是将试样 (40mm× 6mm× 2mm)浸入到pH为 7.4的磷酸盐缓冲溶液 (3 7± 0 .2℃ )中 ,试样定时取出并进行各项性能测试。研究发现聚dl 丙交酯 /羟基磷灰石复合材料在体内外降解中分子量、力学性能首先大幅度下降 ,重量损失滞后 ,体内降解速率稍快于体外 ,但均为简单本体水解 ;羟基磷灰石延缓了复合材料的降解速率。SEM显示聚dl 丙交酯 /羟基磷灰石块状材料内部降解与吸收速率快于表层 ,表现为“双态降解”特征。     

乙交酯/丙交酯/己内酯三元共聚物的合成及表征

生物降解性高分子具有在生理条件下可以自行降解、最终被降解为单体或成为二氧化碳和水,从而或被机体吸收、或通过代谢途径排出体外的特性,已被广泛用作药物释放体系的载体、手术缝合线、外科手术及组织修复材料等各个方面,是当前生物医用高分子的一个重要分支．脂肪族聚酯由于具有良好生物相容性而成为最引人注意和有发展前途的一类生物降解性高分子,其中聚乙交酯（ＰＧＡ）、聚丙交酯（ＰＬＡ）及丙交酯／乙交酯共聚物（ＰＬＧＡ）是这一类聚酯中应用最为广泛的几种．Ｍｉｌｌｅｒ等［１］研究发现乙交酯（ＧＡ）和丙交酯（ＬＡ）共聚…     

新型PLA-PVP两亲性共聚物的生物相容性

通过溶血试验、动态凝血试验、血小板吸附试验、细胞毒性试验,对新型PLA—PVP两亲性共聚物的生物相容性进行了研究,并考察了共聚物的组成对其生物相容性的影响。结果表明,共聚物的溶血率、凝血程度、血小板吸附和变形情况均符合生物材料生物学评价标准,并且,随单体投料比中亲水性单体NVP舍量增大,共聚物的血液相容性有所提高;细胞毒性试验结果显示共聚物对细胞无毒性,对其生长无明显抑制作用。共聚物中引入亲水性PVP链段后,与单一的PLA材料相比较,生物相容性得到改善。     

纳米羟基磷灰石/丝素蛋白复合支架材料的降解特性及生物相容性研究

应用共混法制备了纳米羟基磷灰石/丝素蛋白复合支架材料, 通过体外降解和细胞培养实验研究了复合支架材料的降解特性和生物相容性. 体外降解实验结果显示, 复合支架材料具有稳定的降解能力; 在降解过程中, 羟基磷灰石由于与降解液发生钙、磷等离子的交换, 使其结晶得到了进一步生长和完善. 利用细胞计数法、四甲基偶氮唑盐(MTT)比色法和碱性磷酸酶(ALP)活性测定等分析了复合支架材料的生物相容性, 结果表明, MG63细胞在复合支架材料上具有良好的粘附、增殖能力, 并可引起早期的骨分化. 因此, 纳米羟基磷灰石/丝素蛋白复合支架作为骨组织工程的支架材料具有良好的应用前景.     

丙交酯-乙交酯共聚物的亲水性能研究

以丙交酯和乙交酯为原料,PEG-800为引发剂,采用开环聚合方法合成了具有不同单体比例的共聚物。通过IR、1 H-NMR表征了聚合物的结构,应用GPC技术分析了不同单体组成对共聚物分子量及其分布的影响;通过接触角测定的方法考察了不同单体比例组成对其共聚物的亲水性能影响;通过吸水实验,表明随着乙交酯含量的增强,共聚物的吸水性增强。只要引发剂的含量一定,单体丙交酯、乙交酯摩尔比为3∶1的聚合物膜的吸水性能较好。     

高效液相色谱法测定聚丙交酯乙交酯支架涂层的体外降解产物的含量北大核心CSCD

为了考察新型可吸收锌合金药物洗脱冠脉支架系统(简称支架)中聚合物涂层的体外降解性能,进行了题示项目的研究。将支架悬吊于50 mL离心管中,用已预热至37℃的10 mL磷酸盐缓冲液浸没,并于37℃振荡。分别在0,7,14,21,28 d时取降解液,用磷酸调节pH至2.8±0.2,经0.20μm滤膜过滤后采用高效液相色谱法测定,并对降解过程中支架的表观形貌进行观察,进而评估药物涂层的降解情况。结果表明,降解产物乙醇酸和L-乳酸的质量浓度在一定范围内与其峰面积呈线性关系,检出限(3S/N)分别为0.50,0.70 mg·L^(-1)。对空白加标水样进行精密度试验,相对标准偏差(n=6)为0.12%~2.7%。对空白样品进行加标回收试验,回收率为91.6%~118%。由降解产物的累积量可知,28 d支架中的聚合物涂层基本完全降解。     

乙酰化淀粉/DL-丙交酯接枝共聚物的合成及降解性能研究

用醋酸乙烯酯和玉米淀粉反应制备出了不同取代度乙酰化淀粉，再用乙酰化淀粉同DL－丙交酯接枝共聚合成乙酰化淀粉／DL－丙交酯接枝共聚物。研究了原料配比，淀粉取代度对接枝反应单体转化率（C％），接枝率（G％）接枝效率（GE％）和接枝支链数均分子量（Mn)的影响，结果表明在给定的试验条件下接枝共聚反应的C％，G％，GE％和Mn可分别达到40％，225％，80％和1．4万。接枝共聚物在磷酸缓冲溶液和户外土壤掩埋降解实验表明，在160天内样品失重率分别为71％和60％，表明合成的乙酰化淀粉／DL－丙交酯接枝共聚物具有很好的降解性能。     

低左旋度聚丙交酯的分子结构及体外降解行为研究

以辛酸亚锡为催化剂,135℃下低左旋度的l-丙交酯([a]_(Na)~(25)=—231°)开环聚合制备了低左旋度聚(l-丙交酯)[l-PLLA]([a]_(CHCl_3)~(25)=-119.7°),并用同核去偶~1H-NMR谱表征其分子链结构。用成纤模压法制备了该聚合物的棒材(φ=3.2mm)试样,研究了其在37℃的模拟体液(SBF)中的降解行为。结果表明,l-PLLA具有良好的力学性能,其初始弯曲强度(σ_b)、剪切强度(σ_s)以及弯曲模量(E_b)虽比聚(l-丙交酯)(PLLA)低,但均比聚(dl-丙交酯)(PDLLA)高得多,且材料表现出很好的韧性,呈非晶态,其分子量下降速率和失重速率都介于PLLA和PDLLA之间,可望是一种良好的骨折内固定材料。     

Degradation behavior of poly (l-lactide-co-glycolide) films through gamma-ray irradiation

Gamma-ray irradiation is a very useful tool to improve the physicochemical properties of various biodegradable polymers without the use of a heating and crosslinking agent. The purpose of this study was to investigate the degradation behavior of poly (l-lactide-co-glycolide) (PLGA) depending on the applied gamma-ray irradiation doses. PLGA films prepared through a solvent casting method were irradiated with gamma radiation at various irradiation doses. The irradiation was performed using 60Co gamma-ray doses of 25–500 kGy at a dose rate of 10 kGy/h.The degradation of irradiated films was observed through the main chain scission. Exposure to gamma radiation dropped the average molecular weight (M_n and M_w), and weakened the mechanical strength. Thermograms of irradiated film show various changes of thermal properties in accordance with gamma-ray irradiation doses. Gamma-ray irradiation changes the morphology of the surface, and improves the wettability. In conclusion, gamma-ray irradiation will be a useful tool to control the rate of hydrolytic degradation of these PLGA films.     

In vitro Degradation and Biocompatibility of Ca-P Coated Magnesium Alloy

Calcium-phosphate compounds(Ca-P) coating was prepared on an Mg-Al alloy(AZ60). Biodegradation of Ca-P coated magnesium alloy was evaluated in simulated body fluid(SBF) by examining the changes in magnesium ion concentration and pH value, which indicated that the Ca-P coating on magnesium alloy strongly affected the corrosion of magnesium alloy. Osteoblast MC3T3-E1 cells were utilized to investigate the cellular cytocompatibility. The cytocompatibility was measured by carrying out a series of tests, such as cholecystokinin-octapeptide(CCK-8) test, alkaline phosphatase activity(ALP) test, cellular morphology of hematoxylin-eosin(HE) staining and the induction of apoptosis. It was found that the cell function showed better in the Ca-P coated Mg-alloy extract than in the uncoated magnesium alloy extract. In summary, the results indicate that the Ca-P coating can improve the corrosion resistance of magnesium alloy and elevate cellular proliferation and differentiation of osteoblast MC3T3-E1 cells.     

A comparison of the increased temperature accelerated degradation of Poly(d,l-lactide-co-glycolide) and Poly(l-lactide-co-glycolide)

Bioresorbable polymers composed of Poly(lactide), Poly(glycolide) and their related copolymers have become increasingly popular for the preparation of bone substitute constructs. In vitro tests assessing the degradative changes in physicochemical, mechanical, and biological properties of bioresorbable polymers are generally carried out at 37 °C, in pH 7.4 phosphate-buffered saline (PBS). However, long degradation times, varying from months to years make it difficult to assess these polymers at their late stages of degradation. An increased temperature accelerated degradation methodology, that simulates the long-term degradation of Poly(d,l-lactide-co-glycolide) and Poly(l-lactide-co-glycolide), has been validated in this study. Samples were degraded in PBS, under sterile conditions. Degradation temperatures of 47 °C, 57 °C and 70 °C were selected and compared to physiological temperature, 37 °C. At predetermined time intervals, samples were retrieved and evaluated for changes in mass, swelling, molecular weight, crystallinity, and thermal properties. The results from this study suggest that the degradation mechanism at elevated temperatures is similar to that observed at 37 °C. It is recommended that 47 °C is adopted by the research community to accelerate the degradation of these polymers. It is hoped the application of this methodology could be used as a valuable tool, prior to the assessment of the long-term biocompatibility of these polymers.     

体外电化学测试对镁合金体内降解行为的预测

可生物降解镁合金因同时具有优良的生物相容性和力学性能,在生物医学界显示出其作为新型骨科内植入物的巨大潜在优势和市场前景。目前,作为制约镁合金医用产业化的关键因素,即过快的降解速率已经成为研究重点。本文回顾了体外电化学测试技术对镁合金抗腐蚀性能的研究,并分析了模拟腐蚀体系对镁合金腐蚀行为的影响;同时评估了电化学测试方法作为快速有效预测镁合金体内降解性能前期分析手段的可行性与局限性。最后,对如何发展更合理的体外电化学测试技术来预测镁合金体内降解提出了可能的解决方法及构思。     

In vitro and in vivo characterization of huperzine a loaded microspheres made from end-group uncapped poly(d,l-lactide acid) and poly(d,l-lactide-co-glycolide acid)

The purpose of this work was to develop biodegradable microspheres for long term delivery of a potent acetyl cholinesterase inhibitor, huperzine A (Hup-A), which is of interest in the palliative treatment of Alzheimer's disease. Microspheres were successfully prepared with specifically end-group uncapped poly(d,l-lactide acid) and poly(d,l-lactide-co-glycolide acid) using a simple o/w solvent evaporation method. The morphology, particle size and size distribution, drug loading capacity, drug entrapment efficiency (EE) and in vitro drug release were studied in detail. It was found that the terminal group and the inherent viscosity (IV) of the polymers played key role in the drug encapsulation: higher EE was achieved with end-group uncapped and low IV polymers. In vitro drug release from microspheres made from the selected three kinds of polymers revealed sustained release of Hup-A without significant burst release. Preliminary pharmacokinetic study following subcutaneous injection of Hup-A loaded microspheres illustrated the sustained release of the drug over 6-8 weeks at clinically relevant doses in vivo. The studies demonstrated the feasibility of long term delivery of Hup-A using biodegradable microspheres.     

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。     

聚乳酸眼科植入材料的制备及其降解性能

聚乳酸眼科植入材料的制备及其降解性能卓仁禧＊尹超吴颖楠祝磊曾水清（武汉大学化学系武汉４３００７２）（同济医科大学附属协和医院武汉）关键词聚乳酸，制备，生物可降解性，眼科植入材料１９９６－０８－１８收稿，１９９７－０１－１７修回国家自然科学基金资助项目...     

Sulfated poly-amido-saccharides (sulPASs) are anticoagulants in vitro and in vivo

Anticoagulant therapeutics are a mainstay of modern surgery and of clotting disorder management such as venous thrombosis, yet performance and supply limitations exist for the most widely used agent – heparin. Herein we report the first synthesis, characterization, and performance of sulfated poly-amido-saccharides (sulPASs) as heparin mimetics. sulPASs inhibit the intrinsic pathway of coagulation, specifically FXa and FXIa, as revealed by ex vivo human plasma clotting assays and serine protease inhibition assays. sulPASs activity positively correlates with molecular weight and degree of sulfation. Importantly, sulPASs are not degraded by heparanases and are non-hemolytic. In addition, their activity is reversed by protamine sulfate, unlike small molecule anticoagulants. In an in vivo murine model, sulPASs extend clotting time in a dose dependent manner with bleeding risk comparable to heparin. These findings support continued development of synthetic anticoagulants to address the clinical risks and shortages associated with heparin.

Heparin mimicking sulfated poly-amido-saccharides (sulPASs) are anticoagulants resistant to heparanases and reversed by protamine sulfate. In an in vivo murine model, sulPASs extend clotting time without the increased risk of bleeding.