An adsorbent for improving anticoagulation effect and its preparation method and application

Abstract

The present invention relates to an adsorbent for improving anticoagulation effect, comprising a carrier and a biomimetic material modified on the carrier, wherein the carrier is a porous polymer cross-linked with styrene-divinylbenzene, and the biomimetic material is a derivative of 3-hydroxybicyclo[3,3,0]heptane containing hydroxyl and / or carboxyl groups. The present invention adopts an anticoagulation method different from the existing conventional one, by chemically modifying the surface of the polymer carrier with a group that is beneficial to reducing platelet aggregation, without coating the surface of the carrier, thereby obtaining an adsorbent for the field of blood purification with good anticoagulation effect.

Description

Technical Field

[0001] The invention relates to the technical field of blood purification, in particular to an adsorbent for improving anticoagulation effect and a preparation method and application thereof. Background Art

[0002] Hemoperfusion is an effective blood purification therapy. Hemoperfusion can be used for acute drug or toxic poisoning, end-stage renal disease (uremia), etc. Clinically, patients on maintenance hemodialysis may appropriately consider combined hemoperfusion therapy, especially those with clinical manifestations caused by protein-bound toxin retention.

[0003] Adsorbent materials used in blood perfusion include activated carbon, synthetic resin materials, etc. When polystyrene porous polymers are used in the field of blood purification, in order to improve the blood compatibility of the polymer, it is generally necessary to physically encapsulate it to improve the blood compatibility of the material, and when polystyrene porous polymers are used as adsorbents in the field of blood purification, they are pre-flushed with heparin and the adsorbent surface is heparinized by adding an anticoagulant.

[0004] The physical coating method improves the blood compatibility of the adsorbent, but it has two disadvantages:

[0005] First, the coating layer will hinder the target toxins from entering the internal pores of the adsorbent. The speed at which the adsorbent adsorbs the target substance is determined by the speed at which the target toxins enter the pores. In this way, the target toxins cannot enter the pores or enter very full pores, which reduces the adsorbent's effect on removing target toxins within a certain treatment period.

[0006] Second, the physical coating method introduces new organic solvents, and the film layer is easy to fall off and enter the blood, causing the particle index to exceed the limit or cause embolism. The material surface is heparinized by adding an external anticoagulant. The external anticoagulant not only acts on the local area where the hemoperfusion device adsorbent is located, but also enters the blood vessels and organs throughout the body with the blood circulation. While inhibiting the risk of coagulation caused by biological materials, it also increases the risk of systemic bleeding, especially for people with bleeding tendency who receive blood purification treatment.

[0007] In order to solve the above problems, the prior art also discloses that heparin is physically or chemically modified on a carrier to improve its blood compatibility and thereby improve the safety of the blood purification material. For example, patent number CN201510482480.4, "A method for improving the anticoagulant property of an adsorbent", achieves an adsorbent with an anticoagulant effect by physically networking and fixing the anticoagulant sodium heparin inside a carrier. However, the combination of heparin and antithrombin AT-III reduces the reversal activity of the anticoagulant, and the anticoagulant activity is also reduced.

[0008] The present invention proposes a new method for improving the blood compatibility and anticoagulant effect of an adsorbent based on the following coagulation and thrombosis mechanisms. No coating treatment is required on the surface of the carrier, thereby obtaining an adsorbent with good anticoagulant effect for the field of blood purification. Summary of the invention

[0009] The purpose of the present invention is to provide an adsorbent with improved anticoagulant effect to solve the problem of increased systemic bleeding caused by the addition of anticoagulants. Another purpose of the present invention is to provide a preparation method and application of an adsorbent with improved anticoagulant effect.

[0010] To achieve the above object, the present invention adopts the following technical solutions:

[0011] An adsorbent for improving anticoagulation effect comprises a carrier and a bionic compound modified on the carrier, wherein the carrier is a styrene-divinylbenzene cross-linked porous polymer, the particle size of the styrene-divinylbenzene cross-linked porous polymer is 0.6-1.4 mm, and the pore size is 4-100 nm; the amino substituent on the styrene-divinylbenzene cross-linked porous polymer is 6-aminocaproic acid or γ-aminobutyric acid, and the bionic compound is prostacyclin.

[0012] The adsorbent for improving anticoagulation effect, preferably, the mass ratio of the bionic compound to the carrier is (0.2-1):1.

[0013] The adsorbent for improving the anticoagulation effect, preferably, the amount of the bionic compound modified on the surface of each gram of the adsorbent is 0.1-0.8 mg.

[0014] A method for preparing an adsorbent for improving anticoagulation effect comprises the following steps:

[0015] Preparation of styrene-divinylbenzene cross-linked porous polymers;

[0016] The styrene-divinylbenzene cross-linked porous polymer bonds the biomimetic compound.

[0017] The invention discloses an application of an adsorbent for improving the anticoagulation effect, which is applied to a blood perfusion device.

[0018] The invention discloses an adsorbent for improving the anticoagulant effect and for removing protein-bound toxins.

[0019] The present invention adopts the above technical solution, which has the following advantages:

[0020] 1. The bonded bionic compound has the effect of reducing platelet aggregation, and the 6-aminocaproic acid modified on the porous polymer has the effect of hemostasis and anti-fibrinolysis. The synergistic effect of the bionic compound and 6-aminocaproic acid can improve the anticoagulant effect while avoiding the chance of bleeding caused by excessive anticoagulation.

[0021] 2. A different anticoagulation method from the conventional one is adopted. By chemically modifying the surface of the polymer carrier with groups that are beneficial to reducing platelet aggregation, there is no need to coat the surface of the carrier, thereby obtaining an adsorbent with good anticoagulation effect for use in the field of blood purification.

[0022] 3. Prostacyclin is an effective platelet aggregation inhibitor that can inhibit platelet adhesion to damaged blood vessel walls and has the characteristics of anti-blood screen formation. By bonding it to the surface of the carrier, a buffer layer is formed between the adsorbent and the plasma protein, which is conducive to reducing the adhesion of the porous polymer surface to the plasma protein through electrostatic repulsion, thereby indirectly reducing the adhesion of platelets to the plasma protein on the porous polymer surface, achieving the anticoagulant effect. The rigid skeleton of the adsorbent bonded with biomimetic compounds is conducive to batch purification and high-pressure steam sterilization, which is conducive to industrial application.

[0023] 4. While improving the anticoagulant effect, it also has a good clearing effect on endogenous protein-bound toxins and exogenous protein-bound toxins.

[0024] 5. The rigid skeleton of the adsorbent is conducive to batch purification treatment and high-pressure steam sterilization, which is conducive to industrial application. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention is clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] 1. Comparative Experimental Design

[0027] 1. Design Example 1, Example 2, Example 3, Example 4, Control Example 1 and Control Example 2, wherein Examples 1-4 are adsorbents that have been flexibly modified to graft biomimetic compounds onto a carrier, and Control Example 1 and Control Example 2 are adsorbents that have not been modified to bond biomimetic compounds. Example 1

[0028] Preparation of porous polymers modified with amino-substituted fatty acids:

[0029] Add 0.4% gelatin aqueous solution to a 1000mL three-necked flask, dissolve and set aside. Take a 500mL three-necked flask, add 71.31g styrene, 5.69g divinylbenzene, 0.687g benzoyl peroxide, 56.135g solvent gasoline, respectively, pass nitrogen for 20min, pour the organic phase into the gelatin aqueous solution, start mechanical stirring to mix the materials evenly, heat to 85℃ and react for 20h to obtain a crude product, remove the residual solvent by rotary evaporation, extract with acetone for 8h, wash with water, filter and dry with ventilation to obtain white spherical particles. Take 40g of white balls in a 500mL three-necked flask, add 8g anhydrous zinc chloride, 200mL of dilute hydrochloric acid solution of methylal, start mechanical stirring to mix the materials, heat to 60℃ and react for 18h to obtain a crude product, extract with ethanol for 12h, boil in boiling water, and wash with water until neutral. After ventilation and drying, take 20 g of the product, add 50 mL of dichloroethane, stir at room temperature for 1 h, slowly heat to 80 ° C and keep warm for 4 h, continue to heat to 90 ° C and keep warm for 2 h, cool to below 40 ° C and distill to recover dichloroethane until there is no odor, extract with ethanol for 48 h, and wash with water until it is no longer turbid.

[0030] Place 10 g of the product in an ice-water bath, add 30 mL of dichloroethane and stir for 2 h, then add 20 mL of 0.5% m-chloroperoxybenzoic acid in batches, stir for 12 h, extract with ethanol for 8 h, wash with water and dry under ventilation. Add 25 mL of 5% 6-aminocaproic acid solution to the dried product, stir at 50 °C for 16 h, wash with water, extract with ethanol for 8 h, wash with water and dry.

[0031] Porous polymer bonded biomimetic compound: 10g of the modified porous polymer obtained in step 1 was added with 40mL of tetrahydrofuran solution of N, N-carbonyldiimidazole, and then 20mL of glycine buffer solution of prostacyclin, stirred at room temperature for 24h, filtered to obtain the product, soaked in an aqueous solution of tetrahydrofuran for 48h, then washed with water, boiled in water and dried to obtain the product. The amount of the biomimetic compound modified on the surface was 0.8mg / g.

[0032] Embodiment 2:

[0033] Preparation of porous polymers modified with amino-substituted fatty acids:

[0034] Add 0.5% gelatin aqueous solution into a 1000mL three-necked flask and dissolve it for later use.

[0035] Take a 500mL three-necked flask, add 60g styrene, 5.184g divinylbenzene, 0.587g benzoyl peroxide, and 47.454g solvent gasoline respectively, pass nitrogen for 20 minutes, pour the organic phase into the gelatin aqueous solution, start mechanical stirring to mix the materials evenly, heat to 90℃ and react for 18 hours to obtain the crude product, rotary evaporation to remove the residual solvent, extract with acetone for 8 hours, wash with water, filter and dry under ventilation to obtain white spherical particles.

[0036] Take 50g of white ball and put it in a 500mL three-necked flask, add 10g of anhydrous zinc chloride and 200mL of dilute hydrochloric acid solution of methylal, start mechanical stirring to mix the materials, raise the temperature to 60℃ and react for 18h to obtain a crude product, extract with ethanol for 12h, boil in boiling water, wash with water until neutral, take 20g of the product after ventilation and drying, add 50mL of dichloroethane, stir at room temperature for 1h, slowly heat to 85℃ and keep warm for 4h, continue to heat to 90℃ and keep warm for 2h, cool to below 40℃ and distill to recover dichloroethane until there is no odor, extract with ethanol for 48h, and wash with water until it is no longer turbid.

[0037] Place 10 g of the product in an ice-water bath, add 30 mL of dichloroethane and stir for 2 h, then add 25 mL of 0.5% m-chloroperoxybenzoic acid in batches, stir for 12 h, extract with ethanol for 8 h, wash with water and then dry under ventilation. Add 25 mL of 4% 6-aminocaproic acid solution to the dried product, stir at 50 °C for 16 h, wash with water, extract with ethanol for 8 h, wash with water and dry.

[0038] Porous polymer bonded biomimetic compound: 10g of the modified porous polymer obtained in step 1 was added with 30mL of tetrahydrofuran solution of N, N-carbonyldiimidazole, and then 15mL of glycine buffer solution of prostacyclin, stirred at room temperature for 24h, filtered to obtain the product, soaked in an aqueous solution of tetrahydrofuran for 48h, then washed with water, boiled in water and dried to obtain the product. The amount of the surface modified biomimetic compound was 0.6mg / g.

[0039] Embodiment 3:

[0040] Preparation of porous polymers modified with amino-substituted fatty acids:

[0041] Add 0.4% gelatin aqueous solution into a 1000mL three-necked flask and dissolve it for later use.

[0042] Take a 500mL three-necked flask, add 70.28g of styrene, 6.114g of divinylbenzene, 0.687g of benzoyl peroxide, and 56.135g of solvent gasoline respectively, pass nitrogen for 20 minutes, pour the organic phase into the gelatin aqueous solution, start mechanical stirring to mix the materials evenly, heat to 85℃ and react for 20 hours to obtain the crude product, rotary evaporation to remove the residual solvent, extract with acetone for 8 hours, wash with water, filter and dry under ventilation to obtain white spherical particles.

[0043] Take 40g of the white ball and put it in a 500mL three-necked flask, add 6g of anhydrous zinc chloride and 200mL of dilute hydrochloric acid solution of methylal, start mechanical stirring to mix the materials, heat to 60℃ and react for 18h to obtain a crude product, extract with ethanol for 12h, boil in boiling water, wash with water until neutral, take 20g of the product after ventilation and drying, add 50mL of dichloroethane, stir at room temperature for 1h, slowly heat to 80℃ and keep warm for 4h, continue to heat to 90℃ and keep warm for 2h, cool to below 40℃ and distill to recover dichloroethane until there is no odor, extract with ethanol for 48h, and wash with water until it is no longer turbid.

[0044] Place 10 g of the product in an ice-water bath, add 30 mL of dichloroethane and stir for 2 h, then add 20 mL of 0.5% m-chloroperoxybenzoic acid in batches, stir for 12 h, extract with ethanol for 8 h, wash with water and dry under ventilation. Add 20 mL of 5% 6-aminocaproic acid solution to the dried product, stir at 50 °C for 24 h, wash with water, extract with ethanol for 8 h, wash with water and dry.

[0045] Porous polymer bonded bionic compound: 10g of the modified porous polymer obtained in step 1, add 30mL of N, N-carbonyldiimidazole tetrahydrofuran solution, then add 15mL of prostacyclin glycine buffer, stir at room temperature for 24h, filter to obtain the product, soak it in tetrahydrofuran aqueous solution for 48h, then wash it with water, boil it in water and dry it. The amount of the surface modified bionic compound is 0.5mg / g.

[0046] Embodiment 4:

[0047] Preparation of porous polymers modified with amino-substituted fatty acids:

[0048] Add 0.4% gelatin aqueous solution into a 1000mL three-necked flask and dissolve it for later use.

[0049] Take a 500mL three-necked flask, add 71.31g styrene, 6.132g divinylbenzene, 0.687g benzoyl peroxide, and 56.192g solvent gasoline respectively, pass nitrogen for 20 minutes, pour the organic phase into the gelatin aqueous solution, start mechanical stirring to mix the materials evenly, heat to 85℃ and react for 20 hours to obtain the crude product, rotary evaporation to remove the residual solvent, extract with acetone for 8 hours, wash with water, filter and dry under ventilation to obtain white spherical particles.

[0050] Take 40g of the white ball and put it in a 500mL three-necked flask, add 8g of anhydrous zinc chloride and 200mL of dilute hydrochloric acid solution of methylal, start mechanical stirring to mix the materials, raise the temperature to 60℃ and react for 18h to obtain a crude product, extract with ethanol for 12h, boil in boiling water, wash with water until neutral, take 20g of the product after ventilation and drying, add 50mL of dichloroethane, stir at room temperature for 1h, slowly heat to 80℃ and keep warm for 4h, continue to heat to 90℃ and keep warm for 2h, cool to below 40℃ and distill to recover dichloroethane until there is no odor, extract with ethanol for 48h, and wash with water until it is no longer turbid.

[0051] Place 10 g of the product in an ice-water bath, add 30 mL of dichloroethane and stir for 2 h, then add 20 mL of 0.5% m-chloroperoxybenzoic acid in batches, stir for 12 h, extract with ethanol for 8 h, wash with water and dry under ventilation. Add 20 mL of 10% γ-aminobutyric acid solution to the dried product, stir at 50 ° C for 24 h, wash with water, extract with ethanol for 8 h, wash with water and dry.

[0052] Porous polymer bonded biomimetic compound: 10 g of the modified porous polymer obtained in step 1 was added

[0053] 30 mL of tetrahydrofuran solution of N, N-carbonyldiimidazole, then add 15 mL of glycine buffer of prostacyclin, stir at room temperature for 24 hours, filter to obtain the product, soak it in an aqueous solution of tetrahydrofuran for 48 hours, then wash it with water, boil it in water and dry it. The amount of the biomimetic compound modified on the surface is 0.4 mg / g.

[0054] Comparative Example 1:

[0055] Add 0.4% gelatin aqueous solution into a 1000mL three-necked flask and dissolve it for later use.

[0056] Take a 500mL three-necked flask, add 71.31g styrene, 5.69g divinylbenzene, 0.687g benzoyl peroxide, and 56.135g solvent gasoline respectively, pass nitrogen for 20 minutes, pour the organic phase into the gelatin aqueous solution, start mechanical stirring to mix the materials evenly, heat to 85℃ and react for 20 hours to obtain the crude product, remove the residual solvent by rotary evaporation, extract with acetone for 8 hours, wash with water, filter and dry under ventilation to obtain white spherical particles.

[0057] Take 40g of the white ball in a 500mL three-necked flask, add 8g of anhydrous zinc chloride, 200mL of dilute hydrochloric acid solution of methylal, start mechanical stirring to mix the materials, heat to 60℃ and react for 18h to obtain a crude product, extract with ethanol for 12h, boil with boiling water, and wash with water until neutral. After ventilation and drying, take 20g of the product, add 50mL of dichloroethane, stir at room temperature for 1h, slowly heat to 80℃ and keep warm for 4h, continue to heat to 90℃ and keep warm for 2h, cool to below 40℃ and distill to recover dichloroethane until there is no odor, extract with ethanol for 48h, and wash with water until it is not turbid.

[0058] Comparative Example 2:

[0059] Add 0.5% gelatin aqueous solution into a 1000mL three-necked flask and dissolve it for later use.

[0060] Take a 500mL three-necked flask, add 60g styrene, 5.184g divinylbenzene, 0.587g benzoyl peroxide, and 47.454g solvent gasoline respectively, pass nitrogen for 20 minutes, pour the organic phase into the gelatin aqueous solution, start mechanical stirring to mix the materials evenly, heat to 90℃ and react for 18 hours to obtain the crude product, rotary evaporation to remove the residual solvent, extract with acetone for 8 hours, wash with water, filter and dry under ventilation to obtain white spherical particles.

[0061] Take 50g of white ball and put it in a 500mL three-necked flask, add 10g of anhydrous zinc chloride and 200mL of dilute hydrochloric acid solution of methylal, start mechanical stirring to mix the materials, raise the temperature to 60℃ and react for 18h to obtain a crude product, extract with ethanol for 12h, boil in boiling water, wash with water until neutral, take 20g of the product after ventilation and drying, add 50mL of dichloroethane, stir at room temperature for 1h, slowly heat to 85℃ and keep warm for 4h, continue to heat to 90℃ and keep warm for 2h, cool to below 40℃ and distill to recover dichloroethane until there is no odor, extract with ethanol for 48h, and wash with water until it is no longer turbid.

[0062] 2. Evaluation of anticoagulant effect

[0063] 1. Platelet adhesion and aggregation test

[0064] When coagulation occurs on the surface of the material, coagulation factors are activated, causing platelets to adhere and aggregate to the material surface. Therefore, the anticoagulant effect of the material can be evaluated by evaluating the platelet count.

[0065] The specific method is as follows:

[0066] 5 mL of blood was collected from healthy volunteers, anticoagulated with 3.8% sodium citrate, and centrifuged at 3000 r / min for 10 min. The adsorbent was added at a ratio of 0.1 g / mL anticoagulated plasma, and the blank was prepared in the same way. The test and blank samples were incubated in a 37°C water bath for 30 min, and the platelet count was determined using an automatic cell analyzer, and the platelet adhesion rate was calculated. The results are shown in Table 1.

[0067] Table 1 Platelet adhesion rate

[0068]

[0069] Note: The platelet count value of the blank group was 203.5×10 9 / L

[0070] It can be seen that the platelet adhesion rate of the adsorbent grafted with the biomimetic compound onto the carrier through flexible modification is within 6%, which is much lower than that of the adsorbent without modified bonded biomimetic compound.

[0071] 2. In vitro thrombosis test

[0072] When coagulation occurs on the surface of the material, platelet adhesion and aggregation trigger the adhesion of the material surface to fibrin, thereby forming a thrombus. The anti-coagulant effect of the material can be evaluated by evaluating the adhesion of the material to plasma fibrin and then evaluating the difficulty of thrombus formation in vitro.

[0073] The specific method is as follows: Take 10 mL of healthy human blood, add 0.4 mL of 3.8% sodium citrate solution for partial anticoagulation, and then inject it into a siliconized glass tube containing an appropriate amount of adsorbent. Prepare a blank in the same way, and add 6250 U / mL heparin sodium solution to the blank tube. Then take the blood and centrifuge it at 6°C, 2000 r / min for 10 minutes, take the upper plasma, and determine the content of residual fibrinogen. The results are shown in Table 2.

[0074] Table 2 Fibrinogen content

[0075]

[0076] It can be seen that there is no significant difference in the fibrinogen content of the carrier modified with bionic compounds compared with the blank group with heparin added, reflecting that thrombus formation is not easy on the surface of the material.

[0077] 3. In vitro clearance of endogenous protein-bound toxins test

[0078] Weigh 1 g of adsorbent into a conical flask, add 10 mL of plasma with a protein-bound indoxyl sulfate concentration of 25 mg / L, place it in a constant temperature water bath oscillator at 37°C and oscillate at a rate of 60 times / min for 2 hours, take the supernatant and use liquid chromatography to detect the concentration of protein-bound indoxyl sulfate before and after adsorption, calculate the decrease rate, and the results are shown in Table 3.

[0079] Table 3 Clearance effect of endogenous protein-bound toxin indoxyl sulfate

[0080]

[0081] Currently, high-flux dialysis cannot remove uremic toxin protein-bound indoxyl sulfate. It can be seen that compared with the unmodified adsorbent, the adsorbent modified with biomimetic compounds has a clearance rate of more than 25% for uremic toxin protein-bound indoxyl sulfate, which is more than twice the clearance effect of the unmodified adsorbent.

[0082] 4. Exogenous protein-bound poison clearance test:

[0083] A standard solution of phenobarbital drug with a concentration of 80 µg / mL was prepared, and the solution was oscillated in a water constant temperature oscillator at 37°C and 60 times / min for 2 h at a ratio of resin: solution = 1:20 (W:V). The concentration of the drug before and after adsorption was detected, and the decrease rate of phenobarbital was calculated.

[0084] A standard solution of 80 µg / mL was prepared using dimethoate (purity 97%). The solution was oscillated in a water constant temperature oscillator at 37°C and 60 times / min for 2 h at a ratio of resin: solution = 1:30 (W:V). The concentration of dimethoate before and after adsorption was detected, and the decrease rate of dimethoate was calculated.

[0085] The comparison results are shown in Table 4.

[0086] Table 4 Effect of removing exogenous poisons

[0087]

[0088] Phenobarbital is an exogenous poison that has a wide inhibitory effect on the central nervous system, and its protein binding rate reaches more than 80%. Dimethoate is a herbicide that has great harm to the central nervous system and tissues and organs, and forms toxicity by combining with human protein. As shown in Table 4, the adsorbent prepared by the present invention has a clearance rate of more than 80% for the exogenous protein-bound poison phenobarbital that inhibits toxicity of the central nervous system, and a clearance rate of more than 90% for dimethoate, and the adsorbent has a good scavenging effect on the exogenous protein-bound poison.

[0089] It has a good clearing effect on protein-bound toxins, especially protein-bound indoxyl sulfate with renal and cardiovascular toxicity, and also has a good clearing effect on exogenous protein-bound toxins.

[0090] During the contact between the circulating blood drawn out of the body and the surface of the artificial device during the blood purification process, plasma proteins first interact with the surface of the device / material, and certain protein components are first adsorbed to the surface. Next, platelets in the circulating blood are attracted to the proteins attached to the surface of the device. These platelets adhere and undergo a series of changes, releasing a large number of highly reactive products. The adsorbed plasma proteins and adhered platelets may activate the coagulation and complement pathways, leading to the generation of thrombin and the formation of fibrin. Substances released by platelets and the generation of local thrombin may escalate the above reactions, thereby depositing a large number of platelets wrapped in the fibrin network, leading to the occurrence of coagulation, and red blood cells and white blood cells are also trapped in the fibrin network, thereby forming thrombi at the blood-device interface.

[0091] According to the coagulation and thrombosis mechanism, the present invention designs a buffer substance between the carrier and the contacting plasma protein, and bonds a biomimetic compound having certain properties (groups) identical or similar to those of the protein to the surface of the porous polymer, which is equivalent to introducing a protein-like substance before the porous polymer contacts the blood. Since the porous polymer has the same or similar carboxyl groups as the plasma protein, the electrostatic repulsion generated by the carboxyl groups reduces the attachment of the plasma protein to the porous polymer surface, thereby reducing the possibility of platelets being attracted and attached to the plasma protein surface, thereby reducing the aggregation and adhesion of platelets and improving the anticoagulant effect of the porous polymer.

[0092] Prostacyclin itself is a platelet aggregation inhibitor that can inhibit platelet adhesion to damaged blood vessel walls and has the characteristics of resisting blood sieve formation. By bonding it to the surface of the carrier, a buffer layer is formed between the adsorbent and the plasma protein, which is conducive to reducing the adhesion of the porous polymer surface to the plasma protein through electrostatic repulsion, thereby indirectly reducing the adhesion of platelets to the plasma protein on the porous polymer surface, achieving an anticoagulant effect. The rigid skeleton of the adsorbent bonded with biomimetic compounds is conducive to batch purification and high-pressure steam sterilization, which is conducive to industrial application.

[0093] 6-aminocaproic acid modified on the porous polymer has hemostatic and anti-fibrinolytic effects. The synergistic effect of biomimetic compounds and 6-aminocaproic acid can enhance the anticoagulant effect while avoiding the chance of bleeding caused by excessive anticoagulation.

[0094] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. An adsorbent for improving anticoagulation effect, characterized in that: The invention comprises a carrier and a bionic compound modified on the carrier, wherein the carrier is a styrene-divinylbenzene cross-linked porous polymer, the particle size of the styrene-divinylbenzene cross-linked porous polymer is 0.6-1.4 mm, and the pore size is 4-100 nm; the amino substituent on the styrene-divinylbenzene cross-linked porous polymer is 6-aminocaproic acid or γ-aminobutyric acid, and the bionic compound is prostacyclin.

2. The adsorbent for improving anticoagulation effect according to claim 1, characterized in that: The mass ratio of the bionic compound to the carrier is (0.2-1):

1.

3. The adsorbent for improving anticoagulation effect according to claim 1, characterized in that: The amount of bionic compound modified on the surface of each gram of adsorbent is 0.1~0.8 mg.

4. A method for preparing an adsorbent for improving anticoagulation effect as claimed in any one of claims 1 to 3, characterized in that: The steps include: Preparation of styrene-divinylbenzene cross-linked porous polymers; The styrene-divinylbenzene cross-linked porous polymer bonds the biomimetic compound.

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