新型基體改性濾器膜的制備及抗凝血性能測定
發(fā)布時間:2018-04-15 10:38
本文選題:血液凈化 + 濾器膜。 參考:《中南大學》2014年碩士論文
【摘要】:目的:以聚醚砜(PES)和阿加曲班(Arg)為原料,采用基體改性與浸沒沉淀相轉化方法構建具有抗凝性能的新型基體改性濾器膜。 方法: (1)先后采用乙;磻、氧化反應、酰胺反應對聚醚砜原料進行接枝改性,實現(xiàn)阿加曲班共價接枝于聚醚砜原料上,再將改性的聚醚砜和聚醚砜原料按不同方案進行共混改性,然后利用浸沒沉淀相轉化原理,分別制備聚醚砜膜(PES膜),不加Arg的基體改性膜(PES/CPES膜)和接枝有Arg的新型基體改性膜(PES/Arg-PES膜)。 (2)采用紅外光譜分析方法、核磁共振波譜分析方法和掃描電鏡同步跟蹤檢測新型基體改性濾器膜的制備過程。 (3)以正常人血漿為陰性對照組(Control組),含Arg的血漿為陽性對照組(Arg組),采用全自動凝血檢測儀分別檢測上述三種膜的活化部分凝血活酶時間(APTT)、凝血酶原時間(PT)、凝血酶時間(TT),觀察、評價新型基體改性濾器膜的抗凝血性能。 結果: 1.跟蹤檢測新型基體改性膜材料的制備過程: 1)傅里葉紅外光譜檢測: ①乙;磻,在紅外吸收光譜波數(shù)1678.45cm-1處出現(xiàn)乙;(-COCH3)中C=O的伸縮振動峰,表明-COCH3已被成功引入PES中。 ②氧化反應后,3377.45cm1處出現(xiàn)羧基(-COOH)中O-H的伸縮振動峰,代表-COOH已成功接枝。 ③酰胺反應后,1653.92cm-1處出現(xiàn)肽鍵中C=O的伸縮振動峰,表明PES-COOH上的羧基與Arg上的氨基已經(jīng)發(fā)生酰胺反應,Arg接枝成功。 2)核磁共振波譜檢測: ①乙;磻,化學位移6=2.39處存在-COCH3中-CH3上H的振動峰,表明-CH3接枝成功,接枝率為13.13%。 ②氧化反應后,6=10.69處是-COOH中H的振動峰,加入10μ1重水后-COOH在核磁共振波譜上的信號消失,表明-COOH接枝成功,接枝率為7.19%。 ③酰胺反應后,6=0.4-3.5間出現(xiàn)阿加曲班中-NH2、-NH中H的化學位移,表明阿加曲班已成功接枝于聚醚砜分子上。 2.掃描電鏡觀察膜表面及截面形態(tài):PES膜和改性平面膜均具有由較薄的致密皮層和較為疏松的支撐層構成的非對稱性濾器膜形態(tài)學特點。膜截面均呈指狀孔結構,且新型基體改性膜指狀孔結構穩(wěn)定,指狀孔壁之間廣泛分布有大小不一的孔徑,符合濾器膜的基本形態(tài)要求。 3.抗凝性能檢測: 1)PES膜: PES膜的PT值、TT值相對于正常血漿組顯著縮短(P0.05),表明PES膜可以引發(fā)凝血反應,促進血栓形成。 2)基體改性膜(PES/CPES (2:1)膜): ①PES/CPES (2:1)膜的APTT值、PT值較正常血漿組顯著延長(P0.05),表明PES/CPES (2:1)膜對內(nèi)、外源性凝血途徑具有一定的抑制作用。 ②PES/CPES (2:1)膜的TT值與正常血漿組相比,差異無顯著性,表明PES/CPES (2:1)膜無抗栓作用。 ③PES/CPES (2:1)膜的APTT值、PT值、TT值較PES膜顯著延長(P0.05),表明基體改性能抑制PES膜的促凝、促栓作用。 3)新型基體改性膜(PES/Arg-PES(2:1)膜、PES/Arg-PES(1:1)膜): ①PES/Arg-PES(2:1)膜的APTT值、PT值、TT值較正常血漿組明顯延長(P0.05),表明PES/Arg-PES(2:1)膜不僅對內(nèi)、外源性凝血途徑有抑制作用,而且還能抑制血栓的形成。 ②PES/Arg-PES(1:1)膜的APTT值、PT值、TT值較正常血漿組、PES/CPES (2:1)膜、PES/Arg-PES(2:1)膜顯著延長(P0.05),表明當PES/Arg-PES共混比例為1:1時,抗凝性能更優(yōu)。 結論: (1)以聚醚砜和阿加曲班為原料,采用基體改性和浸沒沉淀相轉化方法,可以成功制備出新型基體改性聚醚砜膜。 (2)新型基體改性聚醚砜膜具有良好的抗凝性能,其中PES/Arg-PES共混比例為1:1時更優(yōu)。
[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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