Anticoagulant adsorption resin, preparation method and application thereof

Abstract

The invention discloses an anticoagulant adsorption resin, a preparation method and application thereof, and relates to the technical field of adsorption materials. A polymer resin with a cross-linked structure is obtained by copolymerization of multiple monomers, and the polymer resin is reacted with heparin after being aminized to introduce amine groups, so as to achieve the purpose of grafting heparin. The synthetic route provided by the invention is simple to operate, low in cost, and has excellent anticoagulant effect. It is also anti-aging and not easy to fall off. In addition, the invention significantly improves the anticoagulant effect by using 1-hydroxybenzotriazole as a condensing agent and polyethyleneimine as an aminating agent.

Description

Technical Field

[0001] The present invention relates to the technical field of adsorption materials, and in particular to an anticoagulant adsorption resin, a preparation method and application thereof. Background Art

[0002] Hemoperfusion involves the extracorporeal circulation of blood through an adsorbent device with broad-spectrum detoxification properties or immobilized specific ligands, removing endogenous or exogenous pathogens from the blood to achieve blood purification. Currently limited to adsorption, hemoperfusion is also known as hemoadsorption. The adsorbent in the hemoperfusion device has a larger contact area with the blood, more easily activating the body's coagulation system and causing clotting, thus often requiring a larger dose of heparin.

[0003] At present, the main processes for grafting heparin on adsorbents are:

[0004] (1) Utilize the chloromethyl groups remaining on the resin to carry out an epoxidation reaction, and then use the epoxidation to carry out a grafting reaction with heparin. This method has many steps, is cumbersome to operate, and is also costly.

[0005] (2) Prepare a polyvinyl pyrrolidone-polymethacrylate-polyacrylic acid triblock copolymer, use this polymer solution to coat the resin, and then graft heparin onto the coated resin. However, the coating has problems such as poor aging resistance and easy shedding, and the coating preparation process is complicated.

[0006] In view of this, the present invention is proposed. Summary of the Invention

[0007] The purpose of the present invention is to provide an anticoagulant adsorption resin, a preparation method and application thereof, aiming to improve the anticoagulant effect of the material while making the preparation process simple, easy and cost-effective.

[0008] The present invention is achieved in that:

[0009] In a first aspect, the present invention provides a method for preparing an anticoagulant adsorption resin, comprising: copolymerizing a plurality of monomers to obtain a polymer resin, aminating the polymer resin to obtain an aminated resin, and grafting heparin onto the aminated resin.

[0010] In an optional embodiment, the condensing agent used in grafting heparin is selected from at least one of 1-hydroxybenzotriazole, 2-(7-azabenzotriazole)-N,N,N",N"-tetramethyluronium hexafluorophosphate, O-benzotriazole-tetramethyluronium hexafluorophosphate, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline;

[0011] Preferably, the condensing agent is 1-hydroxybenzotriazole.

[0012] In an optional embodiment, the process of grafting heparin on the aminated resin comprises: mixing heparin, a condensing agent, a grafting solvent and the aminated resin, and reacting them at 70° C. to 90° C. for 4 h to 8 h;

[0013] Preferably, heparin, a condensing agent and a grafting solvent are first mixed to obtain a mixed solution, and the mixed solution is mixed with an aminated resin for reaction, wherein the mass fraction of heparin in the mixed solution is 0.5%-2%, and the mass fraction of the condensing agent is 0.05%-0.2%;

[0014] The mass ratio of the aminated resin to the mixed solution is 1:9-11;

[0015] Preferably, the grafting solvent is a mixed solvent formed by dimethylformamide and water, and the volume ratio of dimethylformamide to water is 1:8-12.

[0016] In an alternative embodiment, after the reaction of grafting heparin is completed, the product is washed and dried;

[0017] Preferably, the washing is performed multiple times with an organic alcohol solvent and water in sequence, and the drying is performed at 50° C.-70° C. for 10 h-15 h.

[0018] In an optional embodiment, the plurality of monomers include a monomer containing a double bond and a monomer containing an epoxy group, the monomer containing a double bond is selected from at least one of N-vinyl pyrrolidone, styrene and divinylbenzene, and the monomer containing an epoxy group is glyceryl methacrylate;

[0019] Preferably, the plurality of monomers include N-vinyl pyrrolidone, styrene, divinyl benzene and glycerol methacrylate, and the volume ratio of N-vinyl pyrrolidone, styrene, divinyl benzene and glycerol methacrylate is 1-3:4-6:4-6:1.

[0020] In an optional embodiment, a suspension polymerization method is used to prepare a polymer resin, including: mixing an initiator, a plurality of monomers, and an organic solvent to obtain an oil phase solution, mixing the oil phase solution with an aqueous phase solution for reaction, controlling the polymerization temperature to be 70° C. to 90° C., and the polymerization time to be 20 h to 30 h;

[0021] Preferably, after the polymerization reaction is completed, the product is washed and dried in sequence;

[0022] More preferably, the washing is performed by sequentially washing with acetone and ethanol for multiple times, and the drying is performed at 50° C.-70° C. for 10 h-15 h.

[0023] In an optional embodiment, the volume ratio of the total amount of the multiple monomers to the organic solvent is 1.0-1.5:1, the concentration of the initiator in the oil phase solution is 4.5 mg / mL-6.0 mg / mL, and the volume ratio of the oil phase solution to the aqueous phase solution is 1:2-3;

[0024] Preferably, the aqueous phase solution is obtained by mixing a dispersant and water, and the concentration of the dispersant is 8 g / L-15 g / L;

[0025] More preferably, the dispersant comprises polyvinyl alcohol and gelatin, and the mass ratio of polyvinyl alcohol to gelatin is 1:0.5-1.5.

[0026] In an optional embodiment, the process of preparing the aminated resin includes: mixing an aminating agent solution and a polymer resin to react, controlling the reaction temperature to be 50° C.-70° C., and the reaction time to be 4 h-8 h;

[0027] Preferably, the aminating agent solution is an aqueous solution formed by the aminating agent, and the mass ratio of the polymer resin to the aminating agent solution is 1:9-11;

[0028] Preferably, the aminating agent is selected from at least one of polyethyleneimine, ethylenediamine, 1,8-octanediamine, 1,10-diaminodecane and dodecylamine, more preferably polyethyleneimine;

[0029] Preferably, the concentration of the aminating agent in the aminating agent solution is 2 wt%-20 wt%;

[0030] Preferably, after the amination reaction is completed, the product is washed and dried in sequence;

[0031] More preferably, the washing is performed multiple times with an organic alcohol solvent and water in sequence, and the drying is performed at 50° C.-70° C. for 10 h-15 h.

[0032] In a second aspect, the present invention provides an anticoagulant adsorption resin prepared by the preparation method of any one of the aforementioned embodiments.

[0033] In a third aspect, the present invention provides use of the anticoagulant adsorption resin according to the aforementioned embodiment in preparing a blood perfusion adsorption material.

[0034] The present invention has the following beneficial effects: a polymer resin with a cross-linked structure is obtained by copolymerizing multiple monomers, and heparin is grafted onto the polymer resin by introducing amine groups through amination. The synthetic route provided by the present invention is simple to operate, low in cost, and exhibits excellent anticoagulant effects. The polymer resin is also resistant to aging and is not easily detached. DETAILED DESCRIPTION

[0035] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are used. Where the manufacturer of the reagents or instruments is not specified, all are conventional products that can be purchased commercially.

[0036] The present invention provides a method for preparing an anticoagulant adsorption resin, comprising the following steps:

[0037] S1, aggregation

[0038] The cross-linked structure is formed by copolymerizing multiple monomers to obtain a polymer resin. The multiple monomers include monomers containing double bonds and monomers containing epoxy groups, and the cross-linked structure is formed by introducing epoxy groups.

[0039] In some embodiments, the monomer containing a double bond is selected from at least one of N-vinyl pyrrolidone, styrene and divinylbenzene, the monomer containing an epoxy group is glycerol methacrylate, and the monomer is selected from at least one monomer containing a double bond and at least one monomer containing an epoxy group.

[0040] In a preferred embodiment, the multiple monomers include N-vinyl pyrrolidone, styrene, divinylbenzene, and glycerol methacrylate, and the volume ratio of N-vinyl pyrrolidone, styrene, divinylbenzene, and glycerol methacrylate is 1-3:4-6:4-6:1, such as 1:4:4:1, 2:5:5:1, 3:6:6:1, etc., or any value between the above adjacent values. By optimizing the types and ratios of the monomers, the amount of heparin grafted onto the final anticoagulant resin can be increased, which is beneficial to improving the anticoagulant effect.

[0041] In some embodiments, the polymerization method may be, but is not limited to, suspension polymerization. When synthesizing a polymer resin using suspension polymerization, the synthesis process includes: mixing an initiator, multiple monomers, and an organic solvent to obtain an oil phase solution; mixing the oil phase solution with an aqueous phase solution for reaction; and controlling the polymerization temperature to be 70° C. to 90° C. and the polymerization time to be 20 h to 30 h to promote sufficient reaction.

[0042] Specifically, the polymerization temperature can be 70° C., 80° C., 90° C., etc., and the polymerization time can be 20 h, 25 h, 30 h, etc.

[0043] In some embodiments, in order to fully proceed with the polymerization reaction, the inventors optimized the amounts of raw materials, solvents, and initiators: the volume ratio of the total amount of multiple monomers to the organic solvent was 1.0-1.5:1, the concentration of the initiator in the oil phase solution was 4.5 mg / mL-6.0 mg / mL, and the volume ratio of the oil phase solution to the aqueous phase solution was 1:2-3.

[0044] Specifically, the volume ratio of the total amount of multiple monomers and the organic solvent can be 1.0:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, etc., the concentration of the initiator in the oil phase can be 4.5 mg / mL, 5.0 mg / mL, 5.5 mg / mL, 6.0 mg / mL, etc., and the volume ratio of the oil phase solution to the aqueous phase solution can be 1:2, 1:2.5, 1:3, etc.

[0045] In some embodiments, the aqueous phase solution is obtained by mixing a dispersant and water. The concentration of the dispersant is 8 g / L to 15 g / L. The addition of the dispersant facilitates obtaining a uniform polymer. Specifically, the concentration of the dispersant can be 8 g / L, 10 g / L, 12 g / L, 15 g / L, etc.

[0046] In some embodiments, the dispersant includes polyvinyl alcohol and gelatin, and the mass ratio of polyvinyl alcohol to gelatin is 1:0.5-1.5, such as 1:0.5, 1:1.0, 1:1.5, etc.

[0047] In some embodiments, the synthesis process further comprises: washing and drying the product after the polymerization reaction is complete to remove unreacted monomers by washing, and drying to obtain a pure resin material. Washing can be performed multiple times with acetone and ethanol, and the organic solvent for washing is not limited thereto. Drying can be performed at 50°C-70°C for 10-15 hours to fully remove surface moisture and solvent.

[0048] S2. Amination

[0049] The polymer resin is aminated to obtain an aminated resin, and heparin is grafted using the introduced amine groups.

[0050] In some embodiments, the process for preparing the aminated resin includes: mixing an aminating agent solution and a polymer resin for reaction, controlling the reaction temperature to be 50° C. to 70° C. and the reaction time to be 4 to 8 hours to allow the reaction to proceed sufficiently. Specifically, the reaction temperature can be 50° C., 60° C., 70° C., etc., and the reaction time can be 4 hours, 6 hours, 8 hours, etc.

[0051] In some embodiments, the aminating agent is selected from at least one of polyethyleneimine, ethylenediamine, 1,8-octanediamine, 1,10-diaminodecane, and dodecylamine, and may be any one or more of the above. Preferably, the aminating agent is polyethyleneimine. The inventors have found that polyethyleneimine as an aminating agent introduces more amine groups than other aminating agents, which is beneficial for increasing the amount of heparin introduced.

[0052] Furthermore, the aminating agent solution is an aqueous solution of the aminating agent, wherein the concentration of the aminating agent in the aminating agent solution is 2 wt%-20 wt%, and the mass ratio of the polymer resin to the aminating agent solution is 1:9-11, so as to allow the aminating agent to fully react and ensure the amount of amine groups introduced. Specifically, the concentration of the aminating agent in the aminating agent solution can be 2 wt%, 5 wt%, 10 wt%, 15 wt%, 20 wt%, etc., and the mass ratio of the polymer resin to the aminating agent solution can be 1:9, 1:10, 1:11, etc.

[0053] In some embodiments, after the amination reaction is completed, the product is sequentially washed and dried to remove unreacted aminating agent. Washing can be performed multiple times with an organic alcohol solvent and then water, for example, three times with ethanol and three times with water, respectively. Drying can be performed at 50° C. to 70° C. for 10 to 15 hours to fully remove water and solvent.

[0054] S3, grafted heparin

[0055] Heparin is grafted onto the aminated resin, and the amino group on the aminating agent reacts with the carboxyl group on the heparin to introduce heparin, thereby achieving an anticoagulant effect.

[0056] In some embodiments, the condensing agent used in grafting heparin is selected from at least one of 1-hydroxybenzotriazole (HOBt), 2-(7-azabenzotriazole)-N,N,N",N"-tetramethyluronium hexafluorophosphate (HATU), O-benzotriazole-tetramethyluronium hexafluorophosphate (HBTU), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), and can be any one or more of the above.

[0057] In a preferred embodiment, the condensing agent is 1-hydroxybenzotriazole. Compared with other condensing agents, the use of 1-hydroxybenzotriazole as a condensing agent can enable the prepared anticoagulant resin to have a better anticoagulant effect.

[0058] In practice, the process of grafting heparin onto an aminated resin includes mixing heparin, a condensing agent, a grafting solvent, and the aminated resin and reacting them at 70°C-90°C for 4-8 hours to fully react the heparin and ensure the grafted heparin content. Specifically, the reaction temperature can be 70°C, 80°C, 90°C, etc., and the reaction time can be 4 hours, 6 hours, 8 hours, etc.

[0059] In some embodiments, heparin, a condensing agent, and a grafting solvent are first mixed to obtain a mixed solution, which is then reacted with an aminated resin. The mass fraction of heparin in the mixed solution is 0.5%-2%, the mass fraction of the condensing agent is 0.05%-0.2%, and the mass ratio of the aminated resin to the mixed solution is 1:9-11. By controlling the amount of each raw material, the grafted amount of heparin can be increased, thereby enhancing the anticoagulant effect.

[0060] Specifically, the mass fraction of heparin in the mixed solution can be 0.5%, 1.0%, 1.5%, 2.0%, etc., the mass fraction of the condensing agent can be 0.05%, 0.10%, 0.15%, 0.20%, etc., and the mass ratio of the aminated resin to the mixed solution can be 1:9, 1:10, 1:11, etc.

[0061] In some embodiments, the grafting solvent is a mixed solvent of dimethylformamide and water, but is not limited thereto. The volume ratio of dimethylformamide to water can be 1:8-12, such as 1:8, 1:10, 1:12, etc.

[0062] In some embodiments, after the heparin grafting reaction is complete, the product is washed and dried to remove unreacted raw materials. Washing can be performed multiple times with an organic alcohol solvent and then water, such as three times with ethanol and three times with water. Drying can be performed at 50°C-70°C for 10-15 hours to fully remove water and solvent.

[0063] An embodiment of the present invention also provides an anticoagulant adsorption resin, which is prepared by the above-mentioned preparation method. The method is simple, easy and low-cost. The prepared anticoagulant adsorption resin has excellent anticoagulant properties, and the covalently grafted heparin is not easy to fall off, which greatly improves the safety of the resin during use and can be used as a blood perfusion adsorption material.

[0064] The features and performance of the present invention are further described in detail below with reference to the embodiments.

[0065] Example 1

[0066] This embodiment provides a method for preparing an anticoagulant adsorption resin, comprising the following steps:

[0067] (1) Aggregation

[0068] An aqueous solution with a mass fraction of polyvinyl alcohol of 5 g / L and a mass fraction of gelatin of 5 g / L was prepared as the aqueous phase solution of the suspension polymerization reaction system.

[0069] 120 mg of azobisisobutyronitrile was dissolved in a mixed solution containing 2 mL of N-vinylpyrrolidone, 5 mL of styrene, 5 mL of divinylbenzene, 1 mL of methacrylate and 10 mL of n-heptane to serve as the oil phase solution for suspension polymerization.

[0070] The oily mixed solution was added to 60 mL of the aqueous solution to form an oil-water two-phase mixed system. The mixture was stirred at room temperature at 200 rpm for 4 hours, then the temperature was raised to 80°C and the polymerization reaction was carried out for 24 hours. The resulting product was washed three times with acetone and ethanol, respectively, and then vacuum dried at 60°C for 12 hours before use.

[0071] (2)Amination

[0072] Prepare a 2 wt % aqueous solution of polyethyleneimine, add the resin prepared in step (1), the mass ratio of the resin to the aqueous solution of polyethyleneimine is 1:10, react at 60° C. for 6 h, and wash the obtained product with ethanol and water three times in sequence, and then vacuum dry it at 60° C. for 12 h before use.

[0073] (3) Grafted heparin

[0074] Heparin, 1-hydroxybenzotriazole (HOBt), 10 mL of DMF and 100 mL of water are formed into a mixed solution, wherein the concentration of heparin in the mixed solution is 1 wt %, the concentration of 1-hydroxybenzotriazole (HOBt) in the mixed solution is 0.1 wt %, the resin prepared in step (2) is added to the mixed solution, the mass ratio of the resin to the mixed solution is controlled to be 1:10, the reaction is carried out at 80° C. for 6 hours, the product is washed three times with ethanol and water in sequence, and then vacuum dried at 60° C. for 12 hours to obtain an anticoagulant resin.

[0075] Example 2

[0076] The only difference from Example 1 is that HOBt is replaced by an equal amount of 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU).

[0077] Example 3

[0078] The only difference from Example 1 is that HOBt is replaced by an equal amount of O-benzotriazole-tetramethyluronium hexafluorophosphate (HBTU).

[0079] Example 4

[0080] The only difference from Example 1 is that HOBt is replaced by an equal amount of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC).

[0081] Example 5

[0082] The only difference from Example 1 is that HOBt is replaced by an equal amount of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ).

[0083] Example 6

[0084] The only difference from Example 1 is that polyethyleneimine is replaced by an equal amount of ethylenediamine.

[0085] Example 7

[0086] The only difference from Example 1 is that polyethyleneimine is replaced by an equal amount of 1,8-octanediamine.

[0087] Example 8

[0088] The only difference from Example 1 is that polyethyleneimine is replaced by an equal amount of 1,10-diaminodecane.

[0089] Example 9

[0090] The only difference from Example 1 is that polyethyleneimine is replaced by an equal amount of dodecylamine.

[0091] Test example

[0092] The adsorption effect and anticoagulant performance of the adsorption resin materials prepared in the test examples are shown in Table 1 for Examples 1-5, and in Table 2 for Examples 1 and 6-9.

[0093] Test method:

[0094] (1) β2-microglobulin adsorption rate: Each group of adsorbents was added to the plasma of uremic patients obtained clinically, and the plasma was adsorbed according to the ratio of adsorbent: plasma = 1:10 (V / V, i.e., volume ratio). After shaking at 37°C for 2 hours, the adsorption was completed and the plasma was collected for detection.

[0095] (2) Anticoagulant effect test: Fresh dog blood was collected, and each adsorbent was incubated with the freshly collected dog blood at 37°C. The blood coagulation time was observed and recorded.

[0096] Table 1 Effect of condensation agent on resin adsorption performance and anticoagulant effect

[0097]

[0098]

[0099] As shown in Table 1, 1-hydroxybenzotriazole (HOBt) is the most suitable condensing agent in the current system, and has a significant anticoagulant effect. If it is replaced by other condensing agents, the anticoagulant effect will be significantly reduced.

[0100] Table 2 Effect of aminating agent on resin adsorption performance and anticoagulant effect

[0101] Sample number Amination reagent β2-microglobulin adsorption rate Whole blood clotting time Example 1 Polyethyleneimine 90％ ＞6h Example 6 Ethylenediamine 85％ 3min Example 7 1,8-octanediamine 86％ 3min Example 8 1,10-Diaminodecane 84％ 3min Example 9 Dodecylamine 86％ 3min

[0102] As shown in Table 2, polyethyleneimine has the best anticoagulant effect. This may be because polyethyleneimine is rich in amino groups, which are more likely to bond with the carboxyl groups of heparin, resulting in a larger amount of heparin grafted.

[0103] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A method for preparing an anticoagulant adsorption resin, characterized in that: include: A polymer resin is obtained by copolymerizing a plurality of monomers, the polymer resin is aminated to obtain an aminated resin, and heparin is grafted onto the aminated resin; The process of grafting heparin on the aminated resin comprises: mixing heparin, a condensing agent, a grafting solvent and the aminated resin, and reacting at 70° C.-90° C. for 4 h-8 h; The condensing agent is 1-hydroxybenzotriazole; The process of preparing the aminated resin comprises: mixing an aminating agent solution and the polymer resin for reaction, controlling the reaction temperature to be 50° C.-70° C., and the reaction time to be 4 h-8 h; the aminating agent solution is an aqueous solution formed by an aminating agent, and the mass ratio of the polymer resin to the aminating agent solution is 1:9-11; the aminating agent is polyethyleneimine; The multiple monomers include N-vinyl pyrrolidone, styrene, divinyl benzene and glyceryl methacrylate, and the volume ratio of N-vinyl pyrrolidone, styrene, divinyl benzene and glyceryl methacrylate is 1-3:4-6:4-6:

1.

2. The preparation method according to claim 1, characterized in that: First, the heparin, the condensation agent and the grafting solvent are mixed to obtain a mixed solution, and the mixed solution is mixed with the aminated resin for reaction, wherein the mass fraction of the heparin in the mixed solution is 0.5%-2%, and the mass fraction of the condensation agent is 0.05%-0.2%.

3. The preparation method according to claim 2, characterized in that: The mass ratio of the aminated resin to the mixed solution is 1:9-11.

4. The preparation method according to claim 2, characterized in that: The grafting solvent is a mixed solvent formed by dimethylformamide and water, and the volume ratio of dimethylformamide to water is 1:8-12.

5. The preparation method according to claim 4, characterized in that: After the grafting reaction of heparin is completed, the product is washed and dried; the washing is carried out multiple times with an organic alcohol solvent and water in sequence, and the drying is carried out at 50° C.-70° C. for 10 h-15 h.

6. The preparation method according to claim 1, characterized in that: The polymer resin is prepared by a suspension polymerization method, including: mixing an initiator, multiple monomers and an organic solvent to obtain an oil phase solution, mixing the oil phase solution with an aqueous phase solution for reaction, controlling the polymerization temperature to 70°C-90°C, and the polymerization time to 20h-30h.

7. The preparation method according to claim 6, characterized in that: After the polymerization reaction is completed, the product is washed and dried in sequence; the washing is carried out by washing with acetone and ethanol in sequence for multiple times, and the drying is carried out at 50° C.-70° C. for 10 h-15 h.

8. The preparation method according to claim 7, characterized in that: The volume ratio of the total amount of the multiple monomers to the organic solvent is 1.0-1.5:1, the concentration of the initiator in the oil phase solution is 4.5 mg / mL-6.0 mg / mL, and the volume ratio of the oil phase solution to the water phase solution is 1:2-3.

9. The preparation method according to claim 8, characterized in that: The aqueous phase solution is obtained by mixing a dispersant and water, and the concentration of the dispersant is 8g / L-15g / L.

10. The preparation method according to claim 9, characterized in that: The dispersant includes polyvinyl alcohol and gelatin, and the mass ratio of the polyvinyl alcohol to the gelatin is 1:0.5-1.

5.

11. The preparation method according to claim 1, characterized in that: The concentration of the aminating agent in the aminating agent solution is 2wt%-20wt%.

12. The preparation method according to claim 11, characterized in that: After the amination reaction is completed, the product is washed and dried in sequence; the washing is performed by washing with an organic alcohol solvent and water for multiple times in sequence, and the drying is performed at 50° C.-70° C. for 10 h-15 h.

13. An anticoagulant adsorption resin, characterized in that: The composition is prepared by the preparation method according to any one of claims 1 to 12.

14. Use of the anticoagulant adsorption resin according to claim 13 in preparing a blood perfusion adsorption material.

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