Hydrophilic modified blood purification adsorption resin as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of blood purification, and particularly relates to hydrophilic modified blood purification adsorption resin as well as a preparation method and application thereof. According to the hydrophilic modified blood purification adsorption resin provided by the invention, the blood purification adsorption resin such as polystyrene is subjected to hydrophilic modification by using biological polyphenol substances, and the modification is carried out through an epoxy ring-opening grafting reaction, so that the biological polyphenol substances are not easy to fall off; meanwhile, the epoxy ring-opening grafting reaction is controllable and does not cause adverse effects on pore structures of blood purification adsorption resins such as polystyrene, and the used hydrophilic modified substances, namely biological polyphenol substances, are relatively good in blood compatibility and hydrophilicity; therefore, the hydrophilic modified blood purification adsorption resin provided by the invention solves the technical problem of lack of high-performance modified adsorption resin in the prior art.

Description

Technical Field

[0001] The present application belongs to the technical field of blood purification, and in particular relates to a hydrophilically modified blood purification adsorption resin and a preparation method and application thereof. Background Art

[0002] Clinically, blood purification is a technology that uses hemodialysis, hemoperfusion and other means to purify the toxin molecules accumulated in the blood. Blood purification treatment can remove the toxin molecules in the patient's blood, thereby achieving the effect of alleviating and treating the disease. For patients with chronic renal failure, hemodialysis and hemoperfusion can also be used together to remove toxins from the patient's body.

[0003] Clinically, blood perfusion is achieved by establishing an extracorporeal blood circulation circuit, introducing the patient's blood into a blood perfusion device filled with adsorption resin, removing exogenous or endogenous toxins, drugs or metabolic wastes and other target substances through the adsorption action of the adsorption resin, and then returning the treated blood to the body. It can be used to rescue patients poisoned by drugs and poisons. Blood perfusion technology requires the use of blood circuit tubing, injection fluid, and blood perfusion devices filled with adsorption resins. The core component is the adsorption resin. The available adsorption resins are mainly polystyrene adsorption resins, polymethyl methacrylate adsorption resins, polyvinyl alcohol adsorption resins and other adsorption resins. Polystyrene adsorption resins have the advantages of high mechanical strength, good chemical stability, good thermal stability, not easy to fall off, moderate price, mature preparation process, and high adsorption capacity. They are currently the mainstream adsorption resins filled in blood perfusion devices. However, polystyrene adsorption resins have poor blood compatibility. Direct application in blood perfusion can cause adverse reactions such as allergies in patients, limiting their application in blood perfusion. Therefore, researchers will modify the adsorption resins used in blood perfusion devices to improve the blood compatibility of the adsorption resins.

[0004] At present, the modification methods of adsorption resin for hemoperfusion device are mainly divided into physical modification and chemical modification. Physical modification mainly deposits heparin, albumin, xanthan gum, hydroxyethyl cellulose, polyvinyl pyrrolidone and other blood-compatible substances on the surface of adsorption resin to improve the compatibility of polystyrene-based adsorption resin. However, this modification method is physical adsorption, and the deposited coating material has the risk of falling off during clinical application; chemical modification mainly utilizes the double bonds remaining on the surface of adsorption resin to react with hydrophilic monomers such as hydroxyethyl methacrylate, N-alkyl acrylamide, and acrylates to graft a hydrophilic polymer layer on the surface of adsorption resin; but hydroxyethyl methacrylate, Hydrophilic monomers such as N-alkyl acrylamide and acrylates contain active double bonds, which can easily induce secondary free radical polymerization after reacting with the double bonds on the surface of the adsorption resin. The reaction process is difficult to control, and the chain length and thickness of the grafted hydrophilic polymer layer are unpredictable. The pore structure parameters of the modified adsorption resin, such as pore volume, porosity and pore size, cannot be controlled, and the formed pore structure has a risk of clogging. In addition, the safety of the modified raw materials used in the modification process of the adsorption resin for hemoperfusion devices is unknown. Biopolyphenols are derived from plant extracts and have better safety. At the same time, they contain more hydroxyl groups in the molecular chain and have good biocompatibility. They are a potential type of modified raw material for adsorption resins for hemoperfusion devices.

[0005] Therefore, it is necessary to develop new modified adsorption resins to meet the demand for high-performance adsorption resins in the process of blood purification. Summary of the invention

[0006] In view of this, the present application provides a hydrophilic modified blood purification adsorption resin and a preparation method and application thereof, which are used to solve the technical problem of the lack of high-performance modified adsorption resin in the prior art.

[0007] The first aspect of the present application provides a hydrophilically modified blood purification adsorption resin, including an epoxidized blood purification adsorption resin and an aminomethylated biopolyphenolic substance;

[0008] The epoxidized blood purification adsorption resin is grafted with amine-methylated biopolyphenolic substances through an epoxy ring-opening grafting reaction.

[0009] Preferably, the blood purification adsorption resin in the epoxidized blood purification adsorption resin is selected from at least one of polystyrene adsorption resin, polymethyl methacrylate adsorption resin and polyvinyl alcohol adsorption resin.

[0010] Preferably, the biopolyphenolic substance in the aminomethylated biopolyphenolic substance is selected from at least one of 3,4,5-trihydroxybenzoic acid methyl ester, 3,4,5-trihydroxybenzoic acid propyl ester and 3,4,5-trihydroxybenzoic acid n-butyl ester.

[0011] Preferably, the particle size of the blood purification adsorption resin is 300-1000 μm, and the pore size is 6-15 nm.

[0012] The second aspect of the present application provides a method for preparing a hydrophilically modified blood purification adsorption resin, which can be used to prepare the hydrophilically modified blood purification adsorption resin described in the first aspect. The preparation method comprises the following steps:

[0013] The blood purification adsorption resin and the strong oxidant solution are subjected to epoxidation reaction to obtain the epoxidized blood purification adsorption resin;

[0014] The biopolyphenolic substance, the dimethylamine solution and the formaldehyde solution are subjected to an amine methylation reaction to obtain an amine methylated biopolyphenolic substance solution;

[0015] The amine methylated biopolyphenol substance solution and the epoxidized blood purification adsorption resin are subjected to epoxy ring-opening grafting reaction to obtain the hydrophilic modified blood purification adsorption resin.

[0016] Preferably, the strong oxidant solution used in the epoxidation reaction is a hydrogen peroxide solution, a peracetic acid solution or a meta-chloroperbenzoic acid solution, and the mass concentration of the strong oxidant solution is 2-15%;

[0017] The blood purification adsorption resin used is at least one selected from polystyrene adsorption resin, polymethyl methacrylate adsorption resin, and polyvinyl alcohol adsorption resin.

[0018] Preferably, the volume ratio of the blood purification adsorption resin used in the epoxidation reaction to the strong oxidant solution used is 1:1-4.

[0019] Preferably, the epoxidation reaction is carried out at a temperature of 20°C to 30°C and for a time of 2 to 4 hours.

[0020] Preferably, the biopolyphenol substance used in the aminomethylation reaction is selected from at least one of 3,4,5-trihydroxybenzoic acid methyl ester, 3,4,5-trihydroxybenzoic acid propyl ester and 3,4,5-trihydroxybenzoic acid n-butyl ester.

[0021] Preferably, the mass ratio of the biopolyphenols, dimethylamine solution and formaldehyde solution used in the amine methylation reaction is 1:3-4:4-5; the mass concentration of the dimethylamine solution is 25-33%, and the mass concentration of the formaldehyde solution is 25-35%.

[0022] Preferably, the temperature of the amine methylation reaction is 70° C. to 100° C., and the time is 1 to 3 hours.

[0023] Preferably, the volume ratio of the aminomethylated biopolyphenol solution and the epoxidized blood purification adsorption resin used in the epoxy ring-opening grafting reaction is 1-4:1.

[0024] Preferably, the temperature of the epoxy ring-opening grafting reaction is 30° C. to 40° C., and the time is 8 to 16 hours.

[0025] The third aspect of the present application provides the use of the hydrophilically modified blood purification adsorption resin described in the first aspect in the field of blood purification.

[0026] A fourth aspect of the present application provides a blood perfusion device, the interior of which is filled with the hydrophilic modified blood purification adsorption resin described in the first aspect.

[0027] Compared with the prior art, the hydrophilically modified blood purification adsorption resin provided by the present application has at least the following beneficial effects.

[0028] 1. The hydrophilic modified blood purification adsorption resin provided in the present application is chemically modified, and the hydrophilic modified substance is not easy to fall off.

[0029] 2. The hydrophilic modified substance used in the modification of the hydrophilic modified blood purification adsorption resin provided in the present application is a biopolyphenol substance, which has better safety, blood compatibility and hydrophilicity.

[0030] 3. The modification process of the hydrophilically modified blood purification adsorption resin provided in the present application is controllable, has no adverse effect on the pore structure of blood purification adsorption resins such as polystyrene, and has a good ability to adsorb toxin molecules. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the specific implementation methods of the present application or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0032] Figure 1 A schematic diagram of a method for preparing a hydrophilically modified blood purification adsorption resin provided in Examples 1-3 of the present application. DETAILED DESCRIPTION

[0033] The present application provides a hydrophilic modified blood purification adsorption resin and a preparation method and application thereof, which are used to solve the technical problem of the lack of high-performance modified adsorption resin in the prior art.

[0034] The technical solution of the present application will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present application.

[0035] In view of the current physical modification method of depositing heparin and other blood-compatible substances on the surface of the adsorption resin, there is a risk of heparin and other substances falling off the surface of the modified adsorption resin; and the reaction process of the chemical modification method using hydrophilic monomers such as hydroxyethyl methacrylate and double bonds on the surface of the adsorption resin is difficult to control, and the pore structure of the modified adsorption resin is at risk of clogging; there is currently a defect that it is difficult to provide high-performance modified adsorption resins; the present application provides a hydrophilically modified blood purification adsorption resin; the blood purification adsorption resin provided by the present application includes an epoxidized blood purification adsorption resin and an aminomethylated bio-polyphenolic substance; and the epoxidized blood purification adsorption resin is connected to the aminomethylated bio-polyphenolic substance through an epoxy ring-opening grafting reaction.

[0036] In the hydrophilically modified blood purification adsorption resin provided by the present application, the epoxidized blood purification adsorption resin is obtained by reacting the double bonds remaining on the surface of the blood purification adsorption resin with a strong oxidant through an epoxidation reaction, and the double bonds on the surface of the blood purification adsorption resin are oxidized to epoxy groups, and the amine-methylated bio-polyphenolic substances are obtained by reacting the bio-polyphenolic substances through an amine-methylation reaction, and secondary amine groups are introduced into the molecular chains of the bio-polyphenolic substances. Subsequently, the epoxy groups on the surface of the blood purification adsorption resin and the secondary amine groups in the bio-polyphenolic substances undergo an epoxy ring-opening grafting reaction, so that the bio-polyphenolic substances are connected to the blood purification adsorption resin to obtain a hydrophilically modified blood purification adsorption resin; the bio-polyphenolic substances are derived from plant extracts, have good safety, and the bio-polyphenolic substances Phenolic substances contain more hydrophilic groups such as hydroxyl groups, which makes the modified blood purification adsorption resin hydrophilic and blood compatible, which is conducive to the adsorption of toxin molecules; at the same time, the method of modifying the blood purification adsorption resin with biological polyphenols is chemical reaction, not physical modification, and the biological polyphenols are not easy to fall off, and the blood purification adsorption resin has better stability in use; in addition, in the process of epoxy ring-opening grafting reaction in the present application, the secondary amine group participating in the reaction contains only one hydrogen, and the reaction can be interrupted after generating amino alcohol with the epoxy group. The reaction process is controllable and it is difficult to cause adverse effects on the pore structure of the adsorption resin. Therefore, the hydrophilic modified blood purification adsorption resin provided in the present application is a high-performance modified adsorption resin, which overcomes the defect that it is difficult to provide high-performance modified adsorption resins at present.

[0037] As a preferred embodiment, the epoxidized blood purification adsorption resin used in the present application is selected from any one of polystyrene adsorption resin, polymethyl methacrylate adsorption resin and polyvinyl alcohol adsorption resin before the epoxidation reaction, and double bonds remain on the surfaces of polystyrene adsorption resin, polymethyl methacrylate adsorption resin and polyvinyl alcohol adsorption resin; and the bio-polyphenol substances are selected from at least one of 3,4,5-trihydroxybenzoic acid methyl ester, 3,4,5-trihydroxybenzoic acid propyl ester and 3,4,5-trihydroxybenzoic acid n-butyl ester, and the bio-polyphenol substances such as 3,4,5-trihydroxybenzoic acid methyl ester are the esterification products of bio-polyphenol gallic acid (3,4,5-trihydroxybenzoic acid).

[0038] As a preferred embodiment, the particle size of the blood purification adsorption resin used in the present application is 300-1000 μm, and the pore size is 6-15 nm.

[0039] Correspondingly, the present application also provides a method for preparing a hydrophilically modified blood purification adsorption resin, wherein the preparation method first uses a strong oxidant solution to perform an epoxidation reaction on the blood purification adsorption resin to obtain an epoxidized blood purification adsorption resin, and uses a dimethylamine solution, a formaldehyde solution and a bio-polyphenolic substance to perform an amine methylation reaction to obtain an amine methylated bio-polyphenolic substance; then the epoxidized blood purification adsorption resin and the amine methylated bio-polyphenolic substance undergo an epoxy ring-opening grafting reaction to obtain a hydrophilically modified blood purification adsorption resin;

[0040] Among them, in the epoxidation reaction, the reaction temperature is room temperature (20℃~30℃), and the time is 2~4h, while the temperature of the amine methylation reaction is 70℃~100℃, and the time is 1~3h, and the temperature of the epoxy ring-opening grafting reaction is 30℃~40℃, and the time is 8~16h; it can be seen that the method for hydrophilic modification of blood purification adsorption resin provided in the present application has mild overall reaction conditions, without harsh conditions such as high temperature and high pressure, and the required preparation equipment is simple, which is conducive to reducing the preparation cost of hydrophilic modification of blood purification adsorption resin and promoting large-scale commercial application of hydrophilic modified blood purification adsorption resin.

[0041] Correspondingly, the present application also provides the application of a hydrophilically modified blood purification adsorption resin in blood purification, and the specific application is the application of the hydrophilically modified blood purification adsorption resin in blood perfusion technology. On the other hand, it can also be used to adsorb toxin molecules in the body of uremic patients when blood perfusion and hemodialysis are used together to purify the blood of uremic patients.

[0042] Correspondingly, the present application also provides a blood perfusion device, the interior of which is filled with the hydrophilic modified blood purification adsorption resin described in the present application.

[0043] The hydrophilic modified blood purification adsorption resin provided in the present application will be specifically described below in conjunction with embodiments and experimental examples.

[0044] Example 1

[0045] Example 1 of the present application provides a method for preparing a hydrophilically modified blood purification adsorption resin, the preparation method comprising: an epoxidation reaction step, an amine methylation reaction step, and an epoxy ring-opening grafting reaction step.

[0046] The steps of the epoxidation reaction include: weighing 50 mL of polystyrene adsorption resin, adding 50 mL of peracetic acid solution (15 V / V%) to react, reacting at room temperature of 25° C. for 3 hours, and washing with water to obtain the epoxidized polystyrene adsorption resin.

[0047] The steps of the amine methylation reaction include: dissolving 10 g of methyl 3,4,5-trihydroxybenzoate in 60 mL of water, adding 30 g of a dimethylamine aqueous solution (33 wt %), slowly dropping 40 g of a formaldehyde aqueous solution (35 wt %) under stirring, reacting at 85° C. for 1.5 h, and centrifuging to remove the precipitate after the reaction is completed to obtain an amine methylated biopolyphenol solution.

[0048] The steps of the epoxy ring-opening grafting reaction include: adding the aminomethylated biopolyphenol solution to the epoxidized polystyrene adsorption resin in a volume ratio of 1:1, reacting at 35°C for 12 hours, and repeatedly washing with water to obtain a hydrophilically modified blood purification adsorption resin.

[0049] Example 2

[0050] Example 2 of the present application provides a method for preparing a hydrophilically modified blood purification adsorption resin, the preparation method comprising: an epoxidation reaction step, an amine methylation reaction step, and an epoxy ring-opening grafting reaction step.

[0051] The steps of the epoxidation reaction include: weighing 50 mL of polystyrene adsorption resin, adding 50 mL of meta-chloroperbenzoic acid ethanol solution (2V / V%) to react, reacting at room temperature of 25°C for 3 hours, and washing with water to obtain the epoxidized polystyrene adsorption resin.

[0052] The steps of the amine methylation reaction include: dissolving 10 g of ethyl 3,4,5-trihydroxybenzoate in 60 mL of water, adding 35 g of a dimethylamine aqueous solution (30 wt%), slowly dropping 45 g of a formaldehyde aqueous solution (28 wt%) under stirring, reacting at 80° C. for 2 h, and centrifuging to remove the precipitate after the reaction is completed to obtain an amine methylated biopolyphenol solution.

[0053] The steps of the epoxy ring-opening grafting reaction include: adding the aminomethylated biopolyphenol solution to the epoxidized polystyrene adsorption resin at a volume ratio of 2:1, reacting at 35°C for 12 hours, and repeatedly washing with water to obtain a hydrophilically modified blood purification adsorption resin.

[0054] Example 3

[0055] Example 3 of the present application provides a method for preparing a hydrophilically modified blood purification adsorption resin, the preparation method comprising: an epoxidation reaction step, an amine methylation reaction step, and an epoxy ring-opening grafting reaction step.

[0056] The steps of the epoxidation reaction include: weighing 50 mL of polystyrene adsorption resin, adding 400 mL of hydrogen peroxide solution (5 V / V%) for reaction, reacting at room temperature of 25° C. for 3 hours, and washing with water to obtain the epoxidized polystyrene adsorption resin.

[0057] The steps of the amine methylation reaction include: dissolving 10 g of 3,4,5-trihydroxybenzoic acid propyl ester in 60 mL of water, adding 40 g of dimethylamine aqueous solution (25 wt %), slowly dropping 50 g of formaldehyde aqueous solution (25 wt %) under stirring, reacting at 100° C. for 2 h, and centrifuging to remove the precipitate after the reaction is completed to obtain an amine methylated biopolyphenol solution.

[0058] The steps of the epoxy ring-opening grafting reaction include: adding the aminomethylated biopolyphenol solution to the epoxidized polystyrene adsorption resin at a volume ratio of 4:1, reacting at 35°C for 12 hours, and repeatedly washing with water to obtain a hydrophilically modified blood purification adsorption resin.

[0059] Experimental Example 1

[0060] Experimental Example 1 of the present application performs performance tests on the hydrophilically modified blood purification adsorption resin prepared in Examples 1-3, the polystyrene adsorption resin as Comparative Example 1, and the disposable blood perfusion device KCM-350 resin (hydrophilically modified polystyrene resin) as Comparative Example 2. The performance tests include: hemolysis rate test, hydrophilicity test, and toxin molecule clearance rate test; the results of the performance tests are shown in Table 1.

[0061] The process of the hemolysis rate test includes: weighing 2 g of the hydrophilic modified blood purification adsorption resin prepared in Examples 1-3, the polystyrene adsorption resin as Comparative Example 1, and the disposable blood perfusion device KCM-350 resin (hydrophilic modified polystyrene resin) as Comparative Example 2, and injecting 10 mL of normal saline as test samples; placing the test sample tube, the negative tube (only 10 mL of normal saline is injected), and the positive tube (only 10 mL of distilled water is injected) in a 37°C water bath for 30 minutes; adding 0.2 mL of diluted anticoagulated rabbit blood to the test sample tube, the negative tube, and the positive tube, respectively, and gently mixing; continuing to keep warm in a 37°C constant temperature water bath for 60 minutes, pouring out the liquid in the tube after the water bath ends, centrifuging at 800g for 5 minutes, taking the supernatant and placing it in an ultraviolet spectrophotometer, measuring the absorbance value at 545nm, and according to the formula hemolysis rate = 100% * (AB) / (CB) to calculate the hemolysis rate; where A is the absorbance of the test solution; B is the absorbance of the negative control solution; C is the absorbance of the positive control solution.

[0062] The process of the hydrophilicity test includes: drying the hydrophilically modified blood purification adsorption resin prepared in Examples 1-3, the polystyrene adsorption resin as Comparative Example 1, and the disposable blood perfusion device KCM-350 resin (hydrophilically modified polystyrene resin) as Comparative Example 2 at 105°C for 4 hours to remove moisture from the resin; after drying, the resin is ground and then prepared into a sheet sample with a diameter of 13 mm and a thickness of 1 mm using a hydraulic tablet press, and then a contact angle test is performed.

[0063] The process of toxin molecule clearance test includes: preparing phosphate buffer (PBS, pH=7.4) containing 0.1% bovine serum albumin (BSA), and adding β2-microglobulin to the above buffer to prepare a β2-microglobulin solution with a concentration of 10 mg / L; taking 10 mL of the above-prepared β2-microglobulin solution and placing it in a conical flask, weighing 0.2 g of the hydrophilic modified blood purification adsorption resin prepared in Examples 1-3, the polystyrene adsorption resin as Comparative Example 1, and the disposable blood perfusion device KCM-350 resin (hydrophilic modified polystyrene resin) as Comparative Example 2, respectively, and putting them into a conical flask, and placing it in a constant temperature oscillator at a temperature of 37±1°C and oscillating at a rate of 180±10 times / min for 2 hours. After the adsorption is completed, the concentration of the β2-microglobulin solution is measured using a biochemical analyzer, and the adsorption rate is calculated according to the following formula: and according to the formula Cr4=100% * (C0-C t ) / C0 to calculate the clearance rate of β2-microglobulin; where Cr4 is the clearance rate of β2-microglobulin (%), C0 is the concentration of β2-microglobulin solution before adsorption (mg / L), and C t is the concentration of β2-microglobulin solution after adsorption (mg / L).

[0064] Table 1: Results of hemolysis rate test, hydrophilicity test and toxin molecule clearance test

[0065]

[0066] As can be seen from Table 1, the hydrophilically modified blood purification adsorption resin provided in Examples 1-3 of the present application has the lowest hemolysis rate, which is 0.02~0.08%, while the hemolysis rate of KCM-350 resin (hydrophilically modified polystyrene resin) is slightly higher, which is 0.20%, and the unmodified polystyrene adsorption resin has the highest hemolysis rate, which is 0.56%; this shows that the unmodified polystyrene adsorption resin easily causes red blood cell rupture when in contact with blood, and has poor blood compatibility, while the blood compatibility of KCM-350 resin (hydrophilically modified polystyrene resin) is slightly better. The hydrophilically modified blood purification adsorption resin provided in Examples 1-3 of the present application has the best blood compatibility. This may be because the modified raw material used in the present application is a bio-polyphenol substance, and the bio-polyphenol is extracted from plants and has good blood compatibility.

[0067] It can also be seen from Table 1 that the water contact angle of the hydrophilically modified blood purification adsorption resin provided in Examples 1-3 of the present application is 70.3°~74.2°, while the water contact angle of KCM-350 resin (hydrophilically modified polystyrene resin) is 78.5°, and the water contact angle of the unmodified polystyrene adsorption resin is 89.5°, which indicates that the surface of the unmodified polystyrene adsorption resin contains almost no hydrophilic groups, while the surface hydrophobicity of the KCM-350 resin (hydrophilically modified polystyrene resin) is reduced and the hydrophilicity is improved. The hydrophilic modified blood purification adsorption resin provided in Examples 1-3 of the present application has the best hydrophilicity. This is because the modified raw material used in the present application is a bio-polyphenol substance, and the bio-polyphenol contains multiple hydrophilic groups such as hydroxyl groups, and the amino alcohol generated by the reaction of the bio-polyphenol amine with the epoxy group after methylation also has good hydrophilicity, so that the hydrophilic modification effect of the blood purification adsorption resin provided in the present application can be better.

[0068] Furthermore, the hydrophilically modified blood purification adsorption resin, unmodified polystyrene adsorption resin, and KCM-350 resin (hydrophilically modified polystyrene resin) provided in Examples 1-3 of the present application have similar adsorption capacities for toxin molecules, indicating that the hydrophilically modified blood purification adsorption resin provided in Examples 1-3 has a controllable reaction during the preparation process and has no adverse effect on the pore structure of the polystyrene adsorption resin, thereby enabling the hydrophilically modified blood purification adsorption resin provided in Examples 1-3 of the present application to meet the use requirements of adsorption resins for blood perfusion devices.

[0069] The above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some or all of the technical features thereof may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A hydrophilic modified blood purification adsorption resin, characterized in that: Including epoxidized blood purification adsorption resins, aminomethylated biopolyphenols; The epoxidized blood purification adsorption resin is grafted with amine-methylated biopolyphenolic substances through an epoxy ring-opening grafting reaction.

2. A hydrophilic modified blood purification adsorption resin according to claim 1, characterized in that: The blood purification adsorption resin in the epoxidized blood purification adsorption resin is selected from at least one of polystyrene adsorption resin, polymethyl methacrylate adsorption resin and polyvinyl alcohol adsorption resin.

3. The hydrophilic modified blood purification adsorption resin according to claim 1, characterized in that: The biopolyphenolic substance in the aminomethylated biopolyphenolic substance is selected from at least one of 3,4,5-trihydroxybenzoic acid methyl ester, 3,4,5-trihydroxybenzoic acid propyl ester and 3,4,5-trihydroxybenzoic acid n-butyl ester.

4. The hydrophilic modified blood purification adsorption resin according to claim 1, characterized in that: The particle size of the blood purification adsorption resin is 300-1000 μm, and the pore size is 6-15 nm.

5. A method for preparing a hydrophilically modified blood purification adsorption resin according to any one of claims 1 to 4, characterized in that: The following steps are involved: The blood purification adsorption resin and the strong oxidant solution are subjected to epoxidation reaction to obtain the epoxidized blood purification adsorption resin; The biopolyphenolic substance, dimethylamine solution and formaldehyde solution are subjected to an amine methylation reaction to obtain an amine methylated biopolyphenolic substance solution; The amine methylated biopolyphenol substance solution and the epoxidized blood purification adsorption resin are subjected to epoxy ring-opening grafting reaction to obtain the hydrophilic modified blood purification adsorption resin.

6. The method for preparing a hydrophilic modified blood purification adsorption resin according to claim 5, characterized in that: The epoxidation reaction is carried out at a temperature of 20°C to 30°C and for a time of 2 to 4 hours.

7. The method for preparing a hydrophilic modified blood purification adsorption resin according to claim 5, characterized in that: The temperature of the amine methylation reaction is 70° C. to 100° C., and the time is 1 to 3 hours.

8. The method for preparing a hydrophilic modified blood purification adsorption resin according to claim 5, characterized in that: The temperature of the epoxy ring-opening grafting reaction is 30° C. to 40° C., and the time is 8 to 16 hours.

9. Use of the hydrophilic modified blood purification adsorption resin according to any one of claims 1 to 4 in the field of blood purification.

10. A blood perfusion device, characterized in that: The interior of the blood perfusion device is filled with a hydrophilic modified blood purification adsorption resin as described in any one of claims 1-4.

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