新型基体改性滤器膜的制备及抗凝血性能测定

发布时间：2018-04-15 10:38

  本文选题：血液净化 + 滤器膜　； 参考：《中南大学》2014年硕士论文

【摘要】：目的：以聚醚砜(PES)和阿加曲班(Arg)为原料,采用基体改性与浸没沉淀相转化方法构建具有抗凝性能的新型基体改性滤器膜。 方法： (1)先后采用乙酰化反应、氧化反应、酰胺反应对聚醚砜原料进行接枝改性,实现阿加曲班共价接枝于聚醚砜原料上,再将改性的聚醚砜和聚醚砜原料按不同方案进行共混改性,然后利用浸没沉淀相转化原理,分别制备聚醚砜膜(PES膜),不加Arg的基体改性膜(PES/CPES膜)和接枝有Arg的新型基体改性膜(PES/Arg-PES膜)。 (2)采用红外光谱分析方法、核磁共振波谱分析方法和扫描电镜同步跟踪检测新型基体改性滤器膜的制备过程。 (3)以正常人血浆为阴性对照组(Control组),含Arg的血浆为阳性对照组(Arg组),采用全自动凝血检测仪分别检测上述三种膜的活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT),观察、评价新型基体改性滤器膜的抗凝血性能。 结果： 1.跟踪检测新型基体改性膜材料的制备过程： 1)傅里叶红外光谱检测： ①乙酰化反应后,在红外吸收光谱波数1678.45cm-1处出现乙酰基(-COCH3)中C=O的伸缩振动峰,表明-COCH3已被成功引入PES中。 ②氧化反应后,3377.45cm1处出现羧基(-COOH)中O-H的伸缩振动峰,代表-COOH已成功接枝。 ③酰胺反应后,1653.92cm-1处出现肽键中C=O的伸缩振动峰,表明PES-COOH上的羧基与Arg上的氨基已经发生酰胺反应,Arg接枝成功。 2)核磁共振波谱检测： ①乙酰化反应后,化学位移6=2.39处存在-COCH3中-CH3上H的振动峰,表明-CH3接枝成功,接枝率为13.13%。 ②氧化反应后,6=10.69处是-COOH中H的振动峰,加入10μ1重水后-COOH在核磁共振波谱上的信号消失,表明-COOH接枝成功,接枝率为7.19%。 ③酰胺反应后,6=0.4-3.5间出现阿加曲班中-NH2、-NH中H的化学位移,表明阿加曲班已成功接枝于聚醚砜分子上。 2.扫描电镜观察膜表面及截面形态：PES膜和改性平面膜均具有由较薄的致密皮层和较为疏松的支撑层构成的非对称性滤器膜形态学特点。膜截面均呈指状孔结构,且新型基体改性膜指状孔结构稳定,指状孔壁之间广泛分布有大小不一的孔径,符合滤器膜的基本形态要求。 3.抗凝性能检测： 1)PES膜： PES膜的PT值、TT值相对于正常血浆组显著缩短(P0.05),表明PES膜可以引发凝血反应,促进血栓形成。 2)基体改性膜(PES/CPES (2:1)膜)： ①PES/CPES (2:1)膜的APTT值、PT值较正常血浆组显著延长(P0.05),表明PES/CPES (2:1)膜对内、外源性凝血途径具有一定的抑制作用。 ②PES/CPES (2:1)膜的TT值与正常血浆组相比,差异无显著性,表明PES/CPES (2:1)膜无抗栓作用。 ③PES/CPES (2:1)膜的APTT值、PT值、TT值较PES膜显著延长(P0.05),表明基体改性能抑制PES膜的促凝、促栓作用。 3)新型基体改性膜(PES/Arg-PES(2:1)膜、PES/Arg-PES(1:1)膜)： ①PES/Arg-PES(2:1)膜的APTT值、PT值、TT值较正常血浆组明显延长(P0.05),表明PES/Arg-PES(2:1)膜不仅对内、外源性凝血途径有抑制作用,而且还能抑制血栓的形成。 ②PES/Arg-PES(1:1)膜的APTT值、PT值、TT值较正常血浆组、PES/CPES (2:1)膜、PES/Arg-PES(2:1)膜显著延长(P0.05),表明当PES/Arg-PES共混比例为1：1时,抗凝性能更优。 结论： (1)以聚醚砜和阿加曲班为原料,采用基体改性和浸没沉淀相转化方法,可以成功制备出新型基体改性聚醚砜膜。 (2)新型基体改性聚醚砜膜具有良好的抗凝性能,其中PES/Arg-PES共混比例为1：1时更优。
[Abstract]:Objective : To construct a new kind of matrix modified filter membrane with anticoagulant property by using PES and Arg as raw materials .

Method :

( 1 ) carrying out graft modification on the polyether sulfone raw material by adopting the acetylation reaction , the oxidation reaction and the amide reaction , and carrying out blending modification on the modified polyether sulfone and the polyether sulfone raw material according to different schemes , and then carrying out blending modification on the modified polyether sulfone and the polyether sulfone raw material according to different schemes , respectively preparing a polyether sulfone membrane ( PES membrane ) , a matrix modified membrane ( PES / CPES membrane ) without Arg and a novel matrix modified membrane ( PES / Arg - PES membrane ) grafted with Arg .

( 2 ) The preparation process of new matrix modified filter membrane was investigated by means of infrared spectroscopy , nuclear magnetic resonance spectroscopy ( NMR ) and scanning electron microscope ( SEM ) .

( 3 ) In normal control group ( control group ) , the plasma with Arg was positive control group ( Arg group ) , and the activated partial blood coagulation time ( PT ) , prothrombin time ( PT ) and thrombin time ( TT ) of the above three membranes were detected by fully automatic coagulation detector , and the anticoagulant property of the new matrix modified filter membrane was evaluated .

Results :

1 . Tracking and detecting the preparation process of a novel matrix modified membrane material :

1 ) Fourier infrared spectrum detection :

( 1 ) After acetylation , the peak of C = O in acetyl group ( - COCH3 ) was observed at 1678.45cm - 1 of IR absorption spectrum , indicating that - COCH3 was successfully introduced into PES .

( 2 ) After the oxidation reaction , the stretching vibration peak of O - H in carboxyl group ( - COOH ) appeared at 3377.45cm1 , which represented - COOH was grafted successfully .

( 3 ) At 1653.92 cm -1 , the peak of C = O stretching vibration appeared at 1653.92 cm - 1 , indicating that the carboxyl group on PES - COOH and the amino group on Arg had amide reaction and Arg graft was successful .

2 ) Nuclear magnetic resonance spectroscopy detection :

( 1 ) After acetylation , the vibrational peaks of H in - -COCH3 were found at 6 = 2.39 , indicating that - CH3 grafting was successful and the grafting rate was 13.13 % .

( 2 ) After oxidation reaction , 6 = 10.69 is the peak of H in - COOH at 6 = 10.69 . After addition of 10.mu . l of heavy water , the signal on the NMR spectrum disappears , indicating that - COOH grafting is successful and the grafting rate is 7.19 % .

( 3 ) After the amidation reaction , the chemical shifts of - NH2 and - NH were observed in 6 = 0.4 - 3.5 , indicating that the argatroban had been successfully grafted onto the polyether sulfone molecule .

2 . The surface and cross section of the membrane were observed by scanning electron microscope . The PES membrane and the modified planar membrane were characterized by a thinner dense skin layer and a more loose support layer . The membrane cross section is of a finger - like pore structure , and the novel matrix - modified membrane finger - like pore structure is stable , and a large pore size is widely distributed among the finger - like pore walls , and conforms to the basic morphological requirements of the filter membrane .

3 . Anti - coagulation performance detection :

1)PES鑶滐細


The PT value of PES membrane and TT value were significantly shorter than that in normal plasma group ( P0.05 ) , indicating that the PES membrane could induce coagulation reaction and promote thrombosis .

2 ) Substrate - modified membrane ( PES / CPES ( 2 : 1 ) film ) :

( 1 ) The PT value of PES / CPES ( 2 鈭，

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