可释放一氧化氮型聚碳酸酯聚氨酯的性能研究
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摘要
为了提高聚碳酸酯聚氨酯(PCU)的血液相容性,本文通过共混和接枝的方法,使聚碳酸酯聚氨酯膜表面能释放内源性NO,以此来提高材料的抗凝血性。
本文以苯偶酰、邻苯二胺和氯化铜为原料合成了一种亲脂性铜络合物(Cu(II)-DTTCT) , 1H-NMR和光电子能谱测试(XPS)证明结构正确。将Cu(II)-DTTCT共混入PCU膜中,对该膜进行拉伸实验和NO体外释放测试,通过Griess试剂法测试了体系的NO释放情况,考察了各因素对NO释放的影响,同时测试了膜表面Cu的流失情况。拉伸实验结果表明,共混入小分子的PCU膜的最大拉伸强度和杨氏模量增大,断裂伸长率减少。对NO释放进行动力学分析发现在NaNO2浓度为1～5mmol/L、Vc浓度为0.5～3.5mmol/L、Cu用量0～20μmol时,NO的释放速度与NaNO2浓度成一次方,与Vc浓度成三次方,与Cu(II)量成一次方,且影响NO释放的主要因素为NaNO2的浓度。考察各因素对NO释放影响结果表明,软段PCN的分子量为1000时释放速度最大,2000其次,1500最小;PCU厚度的影响归结为Cu/PCU值的影响,该值越大释放越快;当Cu以自由的离子存在时释放最快。膜表面Cu流失的测试结果表明长时间使用时,流失较严重,且以CuCl2形式流失。该膜能在释放环境中连续释放3天,将有很好的应用前景。
选用不同结构的PCU材料涂膜,通过APTES将硝化的L-半胱氨酸(L-CySNO)接枝到膜表面,对该膜进行了ATR-FTIR,SEM,XPS分析和拉伸实验测试,并且考察了不同温度、PCN分子量和膜厚度对NO体外释放的影响。表征结果表明L-CySNO成功地接枝到膜表面;拉伸实验结果表明接枝后的膜力学性能有所下降,但是PCN分子量为1500,2000的PCU膜在接枝以后,机械性能仍然良好,满足生物材料力学性能的要求。体外NO释放实验结果表明NO的释放速率随着温度的升高而增大;随着PCU中PCN分子量的增大,NO的释放速率逐渐降低;而膜的厚度对NO的释放速率没有影响。
利用与接枝L-CySNO类似的方法,将L-精氨酸接枝到PCU膜的表面,ATR-FTIR和XPS分析证明接枝成功。
In order to improve the blood-compatibility of polycarbonate urethane (PCU), the surface of PCU film was forced to generate and release endogenous NO via blending with Cu(II)-complex and grafting endogenous NO donors.
Benzil, o-phenylenediamine and CuCl2 were used to synthesize a kind of lipophilic Cu(II)-complex (Cu(II)-DTTCT). The structure was confirmed by 1H-NMR and X-ray Photoelectron Spectroscopy (XPS). PCU films blended with Cu(II)-DTTCT were characterized by tensile strength measurement and studied in vitro NO releasing. The flux of NO releasing from the PCU films was measured by Griess assay. Different factors were evaluated to study the effects on the NO releasing. The content of Cu leaching from the films was also tested. The tensile measurement showed that peak stress and Young's modulus increased but the break strain decreased after blending with Cu(II)-DTTCT. Kinetics analysis on the in vitro NO releasing indicated that the velocity was proportional to the concentration of nitrite, the cube of concentration of ascorbate and the content of Cu(II) when the concentration of nitrite was between 1 to 5mmol/L, the concentration of ascorbate was between 0.5 to 3.5mmol/L, the content of Cu(II) was between 0 to 20μmol. The concentration of nitrite affected the NO releasing mostly. The NO releasing results also indicated that the releasing velocity was influenced by molecular weight of soft segment. NO released fastest from the surface of the films when the molecular weight of PCN was 1000, 2000 was the second, 1500 was the slowest. The effect of thickness could attribute to the effect of Cu/PCU (wt/wt). The releasing velocity increased as the Cu/PCU increased. The releasing velocity was the largest when the Cu(II) was in presence of Cu2+. The test result of Cu leaching from the film showed that Cu leached seriously from films in presence of CuCl2 when it was used in long-term application. This film could release NO continually for 3 days, which will provide a promising approach that could enable long-term local NO generation at the surface of the medical devices.
S-nitrosocysteine (L-CySNO) was covalently immobilized to the surfaces of films casted by the different PCUs by 3-aminopropyltriethoxysilane (APTES). The modified PCU films were characterized by ATR-FTIR, SEM, XPS and tensile strength measurement. Different environment temperature, molecular weight of PCNs and thickness of films were evaluated to study the effects on the in vitro NO releasing. Results indicated that L-CySNO was grafted to the surfaces successfully; the peak stress and break strain were decreased after modification, but the PCU films with the PCN molecular weight 1500 and 2000 still met the request when it was used in biomedical devices. In vitro NO releasing results showed that with the increase of the environment temperature, the releasing velocity increased; releasing velocity decreased as the molecular weight of PCN increased; however, the thickness of PCU films had no effect on the NO releasing.
L-arginine was grafted onto the surface of PCU films by the similar method used to graft L-CySNO. The product was characterized by ATR-FTIR and XPS. The results conformed to the designed structure.
本文以苯偶酰、邻苯二胺和氯化铜为原料合成了一种亲脂性铜络合物(Cu(II)-DTTCT) , 1H-NMR和光电子能谱测试(XPS)证明结构正确。将Cu(II)-DTTCT共混入PCU膜中,对该膜进行拉伸实验和NO体外释放测试,通过Griess试剂法测试了体系的NO释放情况,考察了各因素对NO释放的影响,同时测试了膜表面Cu的流失情况。拉伸实验结果表明,共混入小分子的PCU膜的最大拉伸强度和杨氏模量增大,断裂伸长率减少。对NO释放进行动力学分析发现在NaNO2浓度为1～5mmol/L、Vc浓度为0.5～3.5mmol/L、Cu用量0～20μmol时,NO的释放速度与NaNO2浓度成一次方,与Vc浓度成三次方,与Cu(II)量成一次方,且影响NO释放的主要因素为NaNO2的浓度。考察各因素对NO释放影响结果表明,软段PCN的分子量为1000时释放速度最大,2000其次,1500最小;PCU厚度的影响归结为Cu/PCU值的影响,该值越大释放越快;当Cu以自由的离子存在时释放最快。膜表面Cu流失的测试结果表明长时间使用时,流失较严重,且以CuCl2形式流失。该膜能在释放环境中连续释放3天,将有很好的应用前景。
选用不同结构的PCU材料涂膜,通过APTES将硝化的L-半胱氨酸(L-CySNO)接枝到膜表面,对该膜进行了ATR-FTIR,SEM,XPS分析和拉伸实验测试,并且考察了不同温度、PCN分子量和膜厚度对NO体外释放的影响。表征结果表明L-CySNO成功地接枝到膜表面;拉伸实验结果表明接枝后的膜力学性能有所下降,但是PCN分子量为1500,2000的PCU膜在接枝以后,机械性能仍然良好,满足生物材料力学性能的要求。体外NO释放实验结果表明NO的释放速率随着温度的升高而增大;随着PCU中PCN分子量的增大,NO的释放速率逐渐降低;而膜的厚度对NO的释放速率没有影响。
利用与接枝L-CySNO类似的方法,将L-精氨酸接枝到PCU膜的表面,ATR-FTIR和XPS分析证明接枝成功。
In order to improve the blood-compatibility of polycarbonate urethane (PCU), the surface of PCU film was forced to generate and release endogenous NO via blending with Cu(II)-complex and grafting endogenous NO donors.
Benzil, o-phenylenediamine and CuCl2 were used to synthesize a kind of lipophilic Cu(II)-complex (Cu(II)-DTTCT). The structure was confirmed by 1H-NMR and X-ray Photoelectron Spectroscopy (XPS). PCU films blended with Cu(II)-DTTCT were characterized by tensile strength measurement and studied in vitro NO releasing. The flux of NO releasing from the PCU films was measured by Griess assay. Different factors were evaluated to study the effects on the NO releasing. The content of Cu leaching from the films was also tested. The tensile measurement showed that peak stress and Young's modulus increased but the break strain decreased after blending with Cu(II)-DTTCT. Kinetics analysis on the in vitro NO releasing indicated that the velocity was proportional to the concentration of nitrite, the cube of concentration of ascorbate and the content of Cu(II) when the concentration of nitrite was between 1 to 5mmol/L, the concentration of ascorbate was between 0.5 to 3.5mmol/L, the content of Cu(II) was between 0 to 20μmol. The concentration of nitrite affected the NO releasing mostly. The NO releasing results also indicated that the releasing velocity was influenced by molecular weight of soft segment. NO released fastest from the surface of the films when the molecular weight of PCN was 1000, 2000 was the second, 1500 was the slowest. The effect of thickness could attribute to the effect of Cu/PCU (wt/wt). The releasing velocity increased as the Cu/PCU increased. The releasing velocity was the largest when the Cu(II) was in presence of Cu2+. The test result of Cu leaching from the film showed that Cu leached seriously from films in presence of CuCl2 when it was used in long-term application. This film could release NO continually for 3 days, which will provide a promising approach that could enable long-term local NO generation at the surface of the medical devices.
S-nitrosocysteine (L-CySNO) was covalently immobilized to the surfaces of films casted by the different PCUs by 3-aminopropyltriethoxysilane (APTES). The modified PCU films were characterized by ATR-FTIR, SEM, XPS and tensile strength measurement. Different environment temperature, molecular weight of PCNs and thickness of films were evaluated to study the effects on the in vitro NO releasing. Results indicated that L-CySNO was grafted to the surfaces successfully; the peak stress and break strain were decreased after modification, but the PCU films with the PCN molecular weight 1500 and 2000 still met the request when it was used in biomedical devices. In vitro NO releasing results showed that with the increase of the environment temperature, the releasing velocity increased; releasing velocity decreased as the molecular weight of PCN increased; however, the thickness of PCU films had no effect on the NO releasing.
L-arginine was grafted onto the surface of PCU films by the similar method used to graft L-CySNO. The product was characterized by ATR-FTIR and XPS. The results conformed to the designed structure.
引文
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