Preparation method of extracorporeal circulation anticoagulant modified membrane

An extracorporeal circulation and anticoagulant technology, applied in the field of medicine, can solve the problems of not being able to directly inhibit the core-Xa factor, aggravating the risk of bleeding in critically ill patients, and the large molecular weight of heparin substances, so as to avoid steric hindrance effects and powerful anticoagulation. coagulation and antithrombotic properties, and the effect of reducing thrombocytopenia

Active Publication Date: 2021-08-10
XIANGYA HOSPITAL CENT SOUTH UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The purpose of the embodiments of the present invention is to provide a method for preparing an anticoagulant modified membrane for extracorporeal circulation, to solve the problem that the anticoagulant modified membrane in the prior art cannot directly inhibit the core of the coagulation pathway-factor Xa, and the existing anticoagulant modified membrane Aggravate the risk of bleeding in critically ill patients, and the drug heparin grafted with extracorporeal circulation membrane material has a large molecular weight and a large spatial conformation, which is not conducive to membrane modification

Method used

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  • Preparation method of extracorporeal circulation anticoagulant modified membrane
  • Preparation method of extracorporeal circulation anticoagulant modified membrane
  • Preparation method of extracorporeal circulation anticoagulant modified membrane

Examples

Experimental program
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Effect test

Embodiment 1

[0032] Step 1, synthesis of carboxylated polysulfone / polyethersulfone

[0033] Dissolve 10g of polysulfone / polyethersulfone in 40ml of NMP and stir to form a homogeneous solution, slowly blow in nitrogen, and then add 4.5g of anhydrous AlCl in sequence 3 , 6ml C 2 h 3 ClO and 100ml NMP, adjust the temperature of the reaction system to 70°C, and react for 2h. The reacted solution was washed 3 times with absolute ethanol and dried to obtain acetylated polysulfone / polyethersulfone (PSf / PES-COCH 3 ).

[0034] 10g of acetylated polysulfone / polyethersulfone (PSf / PES-COCH 3 ) was dissolved in 40ml NMP and stirred to form a homogeneous solution, and then 1g KMnO 4 , 3.7g NaOH, 9g double distilled water, 40ml NMP, adjust the temperature of the reaction system to 70°C, and react for 4h. The reacted solution was washed three times with dilute hydrochloric acid at pH=1 to obtain carboxylated polysulfone / polyethersulfone (PSf / PES-COOH).

[0035] Step 2, synthesis of apixaban modified ...

Embodiment 2

[0041] Step 1, synthesis of carboxylated polysulfone / polyethersulfone:

[0042] Dissolve 10g of polysulfone / polyethersulfone in 40ml of NMP and stir to form a homogeneous solution, slowly blow in nitrogen, and then add 5.5g of anhydrous AlCl in sequence 3 , 8ml C 2 h 3 ClO and 100ml NMP, adjust the temperature of the reaction system to 90°C, and react for 2h. The reacted solution was washed 3 times with absolute ethanol and dried to obtain acetylated polysulfone / polyethersulfone (PSf / PES-COCH 3 ).

[0043] Dissolve 10g acetylated polysulfone / polyethersulfone in 40ml NMP and stir to form a homogeneous solution, then add 1.2g KMnO4, 3.8g NaOH, 9g double distilled water, 40ml NMP in sequence, adjust the temperature of the reaction system to 80°C, and react for 6h . The reacted solution was washed three times with dilute hydrochloric acid at pH=1 to obtain carboxylated polysulfone / polyethersulfone (PSf / PES-COOH).

[0044] Step 2, synthesis of apixaban modified polysulfone / po...

Embodiment 3

[0049] Step 1, synthesis of carboxylated polysulfone / polyethersulfone:

[0050] Dissolve 10g of polysulfone / polyethersulfone in 40ml of NMP and stir to form a homogeneous solution, slowly blow in nitrogen, and then add 5g of anhydrous AlCl in sequence 3 , 7ml C 2 h 3 ClO and 100ml NMP, adjust the temperature of the reaction system to 80°C, and react for 2h. The reacted solution was washed 3 times with absolute ethanol and dried to obtain acetylated polysulfone / polyethersulfone (PSf / PES-COCH 3 ).

[0051] Dissolve 10g acetylated polysulfone / polyethersulfone in 40ml NMP and stir to form a homogeneous solution, then add 1.1g KMnO4, 3.75g NaOH, 9g double distilled water, 40ml NMP in sequence, adjust the temperature of the reaction system to 75°C, and react for 5h . The reacted solution was washed three times with dilute hydrochloric acid at pH=1 to obtain carboxylated polysulfone / polyethersulfone (PSf / PES-COOH).

[0052] Step 2, synthesis of apixaban modified polysulfone / pol...

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Abstract

The invention discloses a preparation method of an extracorporeal circulation anticoagulant modified membrane. The preparation method comprises the following steps: 1, synthesizing carboxylated polysulfone / polyethersulfone; 2, synthesizing apixaban modified polysulfone / polyethersulfone; 3, preparing an apixaban modified polysulfone / polyethersulfone membrane. According to the extracorporeal circulation anticoagulant modified membrane and the preparation method thereof provided by the invention, an Xa factor inhibitor apixaban is grafted to base materials such as polyethersulfone (PES) and polysulfone (PSf), the base materials are modified by the apixaban, and membrane material wall-attached thrombus is efficiently inhibited through signal amplification, so that the membrane has strong anticoagulant and antithrombotic performance. The modification process is simple in synthesis condition, high in controllability and suitable for subsequent industrial large-scale production. According to the novel extracorporeal circulation anticoagulant modified membrane, the steric hindrance effect caused by heparin / heparinoid synthesis is effectively avoided, and meanwhile, the risk of severe bleeding caused by heparin-induced thrombocytopenia (HIT) is reduced.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of an anticoagulant modified membrane for extracorporeal circulation. Background technique [0002] Extracorporeal circulation therapy based on artificial kidney, artificial liver and extracorporeal membrane oxygenation (ECMO) has become an important means of treatment for critical illness. The extracorporeal circulation membrane material is in direct contact with human blood, which is easy to induce coagulation and thrombus, so anticoagulant / antithrombotic treatment must be routinely performed clinically during the above treatments. The contact between membrane material and blood is the initiating factor of blood coagulation in extracorporeal circulation therapy, and the membrane / blood interface is the key part of coagulation and thrombus. The performance of the membrane material determines its biological reaction with human blood, and determin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01D67/00B01D69/02
CPCB01D67/0006B01D67/0093B01D67/0002B01D69/02
Inventor 府晓彭捷洪丹宁建平刘雁峰邹浪汤赐
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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