Adsorbent resin microspheres as well as preparation method and application thereof

Abstract

The invention provides adsorbent resin microspheres as well as a preparation method and application thereof, resin seed microspheres are treated by a modifying agent containing hydrophilic groups, and then are swelled and polymerized to prepare the adsorbent resin microspheres. Hydrophilic modification is carried out in a seed stage before the resin microspheres are formed, hydrophilic groups are still combined on the surfaces of the microspheres along with the swelling process, and the resin microspheres are formed through polymerization; only the outer surfaces of the resin microspheres are modified with hydrophilic groups, and inner pore channels formed in the microsphere polymerization process are not affected, so that the prepared resin microspheres meet the requirements of blood compatibility and adsorption performance.

Description

Technical Field

[0001] This application belongs to the technical field of blood purification, and particularly relates to an adsorbent resin, a preparation method thereof, and an application thereof. Background Art

[0002] Blood purification is a technique that draws a patient's blood out of the body, circulates the blood or plasma through a pump through an adsorbent unit (filter), and then passes through adsorption particles. Through the adsorption effect, various pathogenic factors are removed to purify the blood to prevent and treat diseases. Since the blood is directly in contact with the adsorption particles, very high quality requirements are put forward for the blood compatibility of the adsorption particles. At the same time, in order to ensure the adsorption efficiency, an excellent pore structure of the adsorption particles is also very important.

[0003] At present, synthetic resins have been widely used in the field of blood adsorption due to their high mechanical strength, uniform particle size, adjustable pore channels, etc. However, there are a large number of benzene rings and pendant double bonds on the surface of synthetic resins, resulting in poor hydrophilicity and biocompatibility of the resins, which often lead to clinical risks such as coagulation and sensitization; and the non-specific adsorption of biological macromolecules such as proteins is also relatively high. Therefore, it is necessary to modify their hydrophilicity when applied to the field of blood adsorption.

[0004] Traditional resin modification techniques generally directly perform physical or chemical modification on the resin. For example, the resin is modified by depositing a polymer material with good blood compatibility on the surface of the resin microspheres, including heparin, albumin, PVP, etc.; this modification method is physical adsorption, and there is a risk of shedding of the deposited coating material. In addition, by activating the resin and chemically grafting hydrophilic groups such as carboxyl groups and amino groups, the blood compatibility of the resin can be improved; however, the reaction processes of the grafting modification methods are all difficult to control, and parameters such as the porosity, pore size, and pore volume of the original resin microspheres may change, so the adsorption performance of the resin microspheres will inevitably decay.

[0005] Therefore, it is necessary to develop new adsorption resins to meet the requirements of blood purification for adsorption materials. Summary of the Invention

[0006] The embodiments of this application provide an adsorbent resin, a preparation method thereof, and an application thereof to solve the problems existing in the related technologies. The technical solutions are as follows:

[0007] In the first aspect, the embodiments of this application provide a preparation method of an adsorbent resin microsphere. After the resin seed microsphere is treated with a modifier containing a hydrophilic group, the adsorbent resin microsphere is prepared through swelling and polymerization.

[0008] In one embodiment, the resin seed microsphere is treated with a modifier containing a hydrophilic group to obtain a modified seed microsphere;

[0009] Mix the modified seed microspheres with a swelling agent, add monomers and initiators, and continue swelling;

[0010] After the swelling is completed, add a stabilizer and raise the temperature for polymerization to obtain the adsorbent resin microspheres.

[0011] In one embodiment, the resin seed microspheres are any one of polystyrene, polydivinylbenzene, polyacrylate, or polyacrylonitrile.

[0012] In one embodiment, the particle size of the resin seed microspheres is 10 - 80 μm.

[0013] In one embodiment, the hydrophilic group-containing modifier is any one of polyvinyl alcohol, polyethylene glycol, β-cyclodextrin, nitrocellulose, or phthalic anhydride.

[0014] In one embodiment, the swelling is carried out in the presence of a swelling agent, and the swelling agent is one or a combination of two or more of dibutyl phthalate, toluene, 1-chlorododecane, or N,N-dimethylformamide.

[0015] In one embodiment, the volume ratio of the resin seed microspheres to the swelling agent is 1:2 to 1:7.

[0016] In one embodiment, the volume ratio of the resin seed microspheres to the monomers is 1:9 to 1:20.

[0017] In one embodiment, the stabilizer is polyvinyl alcohol and / or hydroxyethyl cellulose; the addition amount of the stabilizer is 0.5 - 10% of the mass of the monomers.

[0018] In one embodiment, the initiator is one or a combination of two or more of benzoyl peroxide, azobisisobutyronitrile, or tert-butyl peroxy-2-ethylhexanoate.

[0019] In one embodiment, the conditions for polymerization are: the temperature is 60 - 75 °C; the polymerization time is 6 - 36 h.

[0020] In one embodiment, after the polymerization reaction, it further includes a separation and purification step: centrifugally separate the polymerization system and perform solvent extraction for purification.

[0021] In one embodiment, the solvent extraction is sequentially carried out using ethanol, acetone, and purified water for extraction.

[0022] In a second aspect, the embodiments of the present application provide an adsorbent resin microsphere, and the adsorbent microsphere is prepared by the preparation method of any one of the above-mentioned adsorbent resin microspheres.

[0023] In one embodiment, the particle size of the adsorbent resin microspheres is 300 - 600 μm.

[0024] In a third aspect, an embodiment of the present application provides an application of the adsorbent resin microspheres in the field of blood purification.

[0025] The advantages or beneficial effects in the above technical solutions at least include:

[0026] In the preparation method of the adsorbent resin microspheres of the present application, the seed microspheres are first hydrophilically modified, and then the modified seed microspheres are swollen and polymerized to prepare resin microspheres. Hydrophilic modification is carried out at the seed stage before the formation of the resin microspheres. The hydrophilic groups still bind to the surface of the microspheres during the swelling process. After polymerization to form resin microspheres, the hydrophilic groups will not have a great impact on the newly formed pores of the resin microspheres, thus avoiding the possible changes in parameters such as the porosity, pore size, and pore volume of the original resin microspheres caused by the grafting of hydrophilic groups to the resin microspheres after the formation of the resin microspheres, and the attenuation of the adsorption performance of the resin microspheres.

[0027] The adsorbent resin microspheres of the present application have mechanical properties comparable to those of the existing polystyrene resin microspheres for perfusion devices, but have a smaller water contact angle and significantly improved hydrophilicity; and still have good adsorption performance. It meets the data standard requirements for blood purification.

[0028] The above summary is only for the purpose of the specification and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features of the present application will become apparent from the following detailed description. Detailed Embodiments

[0029] In the following, only some exemplary embodiments are simply described. As those skilled in the art can recognize, the described embodiments can be modified in various different ways without departing from the spirit or scope of the present application. Therefore, the description is considered to be exemplary in nature and not restrictive.

[0030] For traditional adsorption microspheres for chemical grafting modification for hydrophilic modification, if direct chemical grafting is carried out on the surface of the microspheres, the modifying groups will also enter the pores of the microspheres during grafting, affecting the adsorption performance of the microspheres. If the polymer monomer and the hydrophilic compound are grafted and modified and then polymerized to prepare microspheres, the presence of the hydrophilic compound will affect the formation of the microspheres. Therefore, how to reduce the influence on the structure or performance of the resin microspheres themselves during the hydrophilic modification process of the resin microspheres is a problem to be solved. Therefore, the present application provides an adsorbent resin microsphere, its preparation method and application to prepare resin microspheres that meet the requirements of both blood compatibility and adsorption performance.

[0031] The embodiment of the present application provides a method for preparing adsorbent resin microspheres. After the resin seed microspheres are treated with a modifier containing hydrophilic groups, the adsorbent resin microspheres are prepared by swelling and polymerization.

[0032] As one of the embodiments, the resin seed microspheres are treated with a modifier containing hydrophilic groups to obtain modified seed microspheres.

[0033] The modified seed microspheres are mixed with a swelling agent, and monomers and initiators are added to continue swelling.

[0034] After the swelling is completed, a stabilizer is added, and the temperature is raised for polymerization to obtain the adsorbent resin microspheres.

[0035] The seed microspheres are first hydrophilically modified and then swollen and polymerized to form the final resin microspheres. The hydrophilic groups are bound to the surface of the seed microspheres. Using the swelling principle, the monomers and initiators enter the interior of the seed microspheres, and the polymerization reaction occurs inside. And as the resin microspheres are formed, only the outer surface of the resin microspheres is modified with hydrophilic groups, without affecting the internal pores formed during the polymerization of the microspheres, thereby generating resin microspheres with both blood compatibility and adsorption performance meeting the requirements.

[0036] As one of the embodiments, the resin seed microspheres are any one of polystyrene, polydivinylbenzene, polyacrylate or polyacrylonitrile. Further, the polyacrylate is methyl polyacrylate or ethyl polyacrylate.

[0037] Microspheres formed by polystyrene, polydivinylbenzene, polyacrylate or polyacrylonitrile are commonly used resin microspheres in the field of perfusion devices. Therefore, when preparing the corresponding resin microspheres, the seed microspheres use the same monomer or polymer material.

[0038] As one of the embodiments, the particle size of the resin seed microspheres is 10 - 80 μm. Regarding the selection of the particle size of the resin seed microspheres, on the one hand, the seed microspheres have a sufficiently large surface area to graft with a sufficient amount of modifier containing hydrophilic groups, so that the finally formed resin microspheres have a smaller water contact angle and the hydrophilicity is significantly improved. On the other hand, it meets the needs of swelling and polymerizing into resin microspheres, and the finally formed resin microspheres are controlled to have a particle size of 300 - 600 μm.

[0039] As one of the embodiments, the modifier containing hydrophilic groups is any one of polyvinyl alcohol, polyethylene glycol, β - cyclodextrin, nitrocellulose, phthalic anhydride. Polyvinyl alcohol, polyethylene glycol, nitrocellulose and β - cyclodextrin contain abundant alcohol hydroxyl groups, so they have good hydrophilicity; the carboxylic acid groups contained in phthalic anhydride can also provide hydrophilicity.

[0040] While polystyrene, divinylbenzene, polyacrylate or polyacrylonitrile can react with phthalic anhydride under catalyst conditions, and the acid anhydride undergoes ring-opening addition to the resin polymer.

[0041] As one of the embodiments, the volume ratio of the resin seed microspheres to the modifier is 1:1 - 1:5. Preferably, the volume ratio of the resin seed microspheres to the modifier is one of 1:1, 1:2, 1:3, 1:4, 1:5 or any range value between any two of them. In this embodiment, the modifier is a solution with a mass concentration of 0.1% - 3%.

[0042] As one of the embodiments, the swelling is carried out in the presence of a swelling agent, and the swelling agent is one or a combination of two or more of dibutyl phthalate, toluene, 1-chlorododecane or N,N-dimethylformamide.

[0043] As one of the embodiments, the volume ratio of the resin seed microspheres to the swelling agent is 1:2 - 1:7. Preferably, the volume ratio of the resin seed microspheres to the swelling agent is one of 1:2, 1:3, 1:4, 1:5, 1:6, 1:7 or any range value between any two of them.

[0044] As one of the embodiments, the volume ratio of the resin seed microspheres to the monomer is 1:9 - 1:20. Preferably, the volume ratio of the resin seed microspheres to the monomer is one of 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20 or any range value between any two of them.

[0045] As one of the embodiments, the stabilizer is polyvinyl alcohol and / or hydroxyethyl cellulose.

[0046] As one of the embodiments, the addition amount of the stabilizer is 0.5% - 10% of the mass of the monomer. Preferably, the addition amount of the stabilizer is one of 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10% or any value between 0.5% and 10%.

[0047] As one of the embodiments, the initiator is one or a combination of two or more of benzoyl peroxide, azobisisobutyronitrile or tert-butyl peroxy-2-ethylhexanoate.

[0048] As one of the embodiments, the polymerization conditions are: the temperature is 60 - 75°C; the polymerization time is 6 - 36 h.

[0049] As one of the embodiments, after the polymerization reaction, a separation and purification step is further included: centrifuging the polymerization system and performing solvent extraction for purification.

[0050] As one of the embodiments, the solvent extraction is sequentially performed using ethanol, acetone, and purified water. Filter and wash successively to remove unreacted monomers and stabilizers.

[0051] The present application also provides an adsorbent resin microsphere, and the adsorbent microsphere is prepared by the preparation method of the adsorbent resin microsphere described in any one of the above.

[0052] As one of the embodiments, the particle size of the adsorbent resin microsphere is 300 - 600 μm.

[0053] As one of the embodiments, the adsorbent resin microsphere of the present application is applied in the field of blood purification.

[0054] Next, further description will be given with specific embodiments.

[0055] Example 1

[0056] Slowly add 20 ml of phthalic anhydride solution with a mass fraction of 0.5% (the solvent is nitrobenzene and dichloromethane with a volume ratio of 1:3) to 5 ml of polystyrene seed microspheres with an average particle size of 20 μm. Ultrasonically oscillate for 10 min for thorough mixing, introduce pure nitrogen, and add catalyst aluminum trichloride under stirring. Keep nitrogen passing and react under normal pressure; after the reaction is completed, soak with tetrahydrofuran to remove unreacted phthalic anhydride; sequentially add methanol and purified water for suction filtration, and vacuum dry to constant weight to obtain carboxyl - modified polystyrene seed microspheres;

[0057] Take 10 ml of dibutyl phthalate and 100 ml of sodium dodecyl sulfate aqueous solution with a mass fraction of 0.25%, ultrasonically disperse them evenly and then add them to the carboxyl - modified polystyrene seed microspheres; keep the temperature at 35°C and swell for 5 h under magnetic stirring; then add 2 g of benzoyl peroxide and 60 ml of styrene, continue to swell for 18 h; add 1.5 g of hydroxyethyl cellulose, raise the temperature to 70°C and polymerize for 24 h; after the polymerization reaction ends, filter and wash successively with ethanol, acetone, and purified water to remove unreacted monomers and stabilizer hydroxyethyl cellulose, and vacuum dry to obtain hydrophilic - modified polystyrene resin microspheres.

[0058] Example 2

[0059] Slowly add 20 ml of phthalic anhydride solution with a mass fraction of 0.5% (the solvent is nitrobenzene and dichloromethane with a volume ratio of 1:3) dropwise into 5 ml of polydivinylbenzene seed microspheres with an average particle size of 50 μm. Ultrasonically oscillate for 10 min for thorough mixing, introduce pure nitrogen, add catalyst aluminum trichloride under stirring, and carry out the reaction under nitrogen flow and normal pressure. After the reaction is completed, soak with tetrahydrofuran to remove unreacted phthalic anhydride. Successively add methanol and purified water for suction filtration, and vacuum dry to constant weight to obtain carboxyl-modified polydivinylbenzene seed microspheres;

[0060] Take 25 ml of toluene and 100 ml of lumbrokinase aqueous solution with a mass fraction of 0.25%, ultrasonically disperse them evenly, and then add them to the carboxyl-modified polydivinylbenzene seed microspheres. Keep the temperature at 35 °C and swell for 5 h under magnetic stirring. Then add 2 g of azobisisobutyronitrile and 45 ml of divinylbenzene, and continue to swell for 18 h. Add 10 ml of 1% polyvinyl alcohol aqueous solution, raise the temperature to 70 °C and polymerize for 24 h. After the polymerization reaction is completed, successively filter and wash with ethanol, acetone, and purified water to remove unreacted monomers and stabilizer polyvinyl alcohol, and vacuum dry to obtain hydrophilic modified polydivinylbenzene resin microspheres.

[0061] Example 3

[0062] Dissolve 5 ml of poly(methyl acrylate) microspheres with an average particle size of 80 μm and 20 ml of 0.5% PEG4000 aqueous solution in the solvent tetrahydrofuran, stir for 1 h for thorough mixing, take out after evaporating the solvent in a vacuum oven at 40 °C, heat and react at 140 °C for 30 min. After the obtained product is cooled to room temperature, soak it in tetrahydrofuran to remove unreacted PEG4000 to obtain PEG-modified poly(methyl acrylate) seed microspheres;

[0063] Take 35 ml of N,N-dimethylformamide and 100 ml of sodium dodecyl sulfate aqueous solution with a mass fraction of 0.25%, ultrasonically disperse them evenly, and then add them to the modified poly(methyl acrylate) seed microspheres. Keep the temperature at 35 °C and swell for 5 h under magnetic stirring. Then add 2 g of benzoyl peroxide and 100 ml of acrylate, and continue to swell for 18 h. Add 10 ml of hydroxyethyl cellulose, raise the temperature to 60 °C and polymerize for 24 h. Filter and wash successively with ethanol, acetone, and purified water to remove unreacted monomers and stabilizer hydroxyethyl cellulose, and vacuum dry to obtain hydrophilic modified poly(methyl acrylate) microspheres.

[0064] Example 4

[0065] Dissolve 5 ml of polyacrylonitrile microspheres with an average particle size of 50 μm and 20 ml of a 1% aqueous solution of polyvinyl alcohol (molecular weight 5000) in the solvent tetrahydrofuran, stir for 1 h to mix evenly, take out after evaporating the solvent in a vacuum oven at 40 °C, heat and react at 140 °C for 30 min, and soak the obtained product in tetrahydrofuran after cooling to room temperature to remove unreacted polyvinyl alcohol to obtain polyvinyl alcohol-modified polyacrylonitrile seed microspheres;

[0066] Take 35 ml of 1-chlorododecane and 100 ml of an aqueous solution of sodium dodecyl sulfate with a mass fraction of 0.25%, disperse them evenly by ultrasonic wave, and add them to the modified poly(methyl acrylate) seed microspheres, keep the temperature at 35 °C, and swell for 5 h under magnetic stirring; then add 2 g of benzoyl peroxide and 100 ml of acrylonitrile, and continue to swell for 18 h; add 10 ml of hydroxyethyl cellulose, raise the temperature to 75 °C and polymerize for 6 h; filter and wash successively with ethanol, acetone, and purified water to remove unreacted monomers and the stabilizer hydroxyethyl cellulose, and vacuum dry to obtain hydrophilic modified polyacrylonitrile microspheres.

[0067] Comparative Example 1

[0068] Slowly drop 20 ml of a 0.5% phthalic anhydride solution (the solvent is nitrobenzene and dichloromethane with a volume ratio of 1:3) into 60 ml of polystyrene resin microspheres with an average particle size of 500 μm, add the catalyst aluminum trichloride under stirring, and carry out the reaction under nitrogen flow and normal pressure; after the reaction is completed, add methanol and purified water successively for suction filtration, and vacuum dry to constant weight to obtain carboxyl-modified polystyrene resin microspheres.

[0069] Comparative Example 2

[0070] Take 10 ml of dibutyl phthalate and 100 ml of an aqueous solution of sodium dodecyl sulfate with a mass fraction of 0.25%, disperse them evenly by ultrasonic wave, and add them to 5 ml of polystyrene seed microspheres, keep the temperature at 35 °C, and swell for 5 h under magnetic stirring; then add 2 g of benzoyl peroxide and 60 ml of styrene, and continue to swell for 18 h; add 2 ml of hydroxyethyl cellulose, raise the temperature to 70 °C and polymerize for 24 h; filter and wash successively with ethanol, acetone, and purified water to remove unreacted monomers and the stabilizer, and vacuum dry to obtain polystyrene resin microspheres;

[0071] Slowly drop 20 ml of a 0.5% phthalic anhydride solution (the solvent is nitrobenzene and dichloromethane with a volume ratio of 1:3) into 60 ml of the prepared polystyrene resin microspheres, add the catalyst aluminum trichloride under stirring, and carry out the reaction under nitrogen flow and normal pressure; after the reaction is completed, add methanol and purified water successively for suction filtration, and vacuum dry to constant weight to obtain modified polystyrene resin microspheres.

[0072] Comparative Example 3

[0073] Take 10 ml of dibutyl phthalate and 100 ml of an aqueous solution of sodium dodecyl sulfate with a mass fraction of 0.25%, disperse them evenly by ultrasonic treatment, and then add them to 5 ml of polystyrene seed microspheres with an average particle size of 20 μm; keep the temperature at 35 °C and swell for 5 h under magnetic stirring; then add 2 g of benzoyl peroxide and 60 ml of styrene, and continue to swell for 18 h; add 2 ml of hydroxyethyl cellulose, raise the temperature to 70 °C and polymerize for 24 h; after the polymerization reaction is completed, filter and wash successively with ethanol, acetone, and purified water to remove the unreacted monomers and the stabilizer hydroxyethyl cellulose, and then dry in vacuum to obtain the swollen polymerized polystyrene resin microspheres.

[0074] Comparative Example 4

[0075] The polystyrene resin microspheres with an average particle size of 500 μm used in Comparative Example 1.

[0076] Performance test:

[0077] 1. Hydrophilicity performance test: Take microsphere samples respectively, dry them at 105 °C for 4 h to remove the moisture in the microspheres, grind them, and prepare sheet samples with a diameter of 13 mm and a thickness of 1 mm using a hydraulic press, and then conduct contact angle tests; the results are shown in Table 1.

[0078] 2. Hemolysis rate test: Test according to the requirements of the standard GB / T16886.4-2003; the results are shown in Table 1.

[0079] 3. Adsorption performance test of β2-microglobulin

[0080] Test method: Freshly prepare a phosphate buffer solution (PBS, pH = 7.4) containing 0.1% bovine serum albumin (BSA), then add an appropriate amount of β2-microglobulin to the PBS to prepare a β2-microglobulin solution with a concentration of 10 mg / L. Then take 10 mL and place it in a conical flask, weigh 0.2 g of the microspheres prepared in the examples and comparative examples and put them into the flask, place them in an environment of (37 ± 1) °C, and oscillate and adsorb in a constant temperature oscillator at a rate of (180 ± 10) times / min for 2 h. Measure the concentration of the β2-microglobulin solution with a biochemical analyzer, and calculate the adsorption rate according to the following formula:

[0081]

[0082] In the formula: C r4 is the β2-microglobulin adsorption rate, in %; C0 is the concentration of the β2-microglobulin solution before adsorption, in mg / L; C t is the concentration of the β2-microglobulin solution after 2 h of adsorption, in mg / L; the results are shown in Table 1.

[0083] 4. Mechanical property test: Detection method of crushing rate. After drying each sample, it is dried at 60 °C for 3 h until the weight loss rate is below 3 wt%. After natural cooling to room temperature, 100 ml of absolute ethanol is added, and it is stirred at a speed of 100 revolutions per minute for 5 min. Then the resin is filtered and sieved. Next, the resin spheres are separated from the fragments, and they are dried at 60 °C for 3 h respectively, and then weighed separately to calculate the crushing rate. Calculation formula: mass of fragments divided by the sum of the mass of resin spheres and fragments, and then multiplied by 100%. The results are shown in Table 1.

[0084] Table 1

[0085]

[0086]

[0087] As can be seen from Table 1, in the examples, the seed microspheres are first hydrophilically modified, and then prepared by swelling and temperature rising polymerization. The contact angle of the prepared resin microspheres is smaller. Compared with the microspheres of Comparative Examples 3 and 4, the contact angle drops from about 90° to less than 71°, and the hydrophilicity is significantly improved. In particular, the hemolysis rate is below 2.1%, far lower than 6.5% of Comparative Example 4, indicating that after modification, the blood compatibility is significantly enhanced. The mechanical properties have no obvious difference from the existing polystyrene resin microspheres for hemoperfusion columns in Comparative Example 4.

[0088] However, through the comparison of adsorption rates, it can be found that the polystyrene resin microspheres in Comparative Example 1 and Comparative Example 2 are directly hydrophilically modified, and their adsorption rates are significantly decreased compared with those in Comparative Example 3 and Comparative Example 4. While for the hydrophilically modified resin microspheres prepared in the examples of the present application, their adsorption rates are not much different from those of the unmodified resin microspheres in Comparative Example 3 and Comparative Example 4. This shows that when the large microspheres in Comparative Example 1 and Comparative Example 2 are modified, the pores of the modified microspheres are blocked, affecting the adsorption effect; while the method of first modifying, then swelling and polymerizing to prepare microspheres in the present application has little influence on the microstructure of the microspheres while having hydrophilic modification, and the modification effect of the adsorption performance is obvious.

[0089] In the description of this specification, the description with reference to terms such as "one embodiment", "some embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more embodiments or examples. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0090] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include at least one such feature. In the description of the present application, "a plurality of" means two or more unless otherwise specifically defined.

[0091] As described above, the above is only a specific embodiment of the present application, but the protection scope of the present application is not limited thereto. Any person skilled in the art within the technical scope disclosed in the present application can easily think of various changes or substitutions, and these should all be covered within the protection scope of the present application. Therefore, the protection scope of the present application shall be subject to the protection scope of the claims.

Claims

1. A method for preparing adsorbent resin microspheres, characterized in that, The adsorbent resin microspheres are prepared by swelling and polymerization after the resin seed microspheres are treated with a modifier containing a hydrophilic group.

2. The preparation method of the adsorbent resin microspheres according to claim 1, characterized in that, It includes the following steps: The resin seed microspheres are treated with a modifier containing a hydrophilic group to obtain modified seed microspheres; The modified seed microspheres are mixed with a swelling agent, and monomers and an initiator are added to continue swelling; After the swelling is completed, a stabilizer is added, and the temperature is raised for polymerization to obtain the adsorbent resin microspheres.

3. The preparation method of the adsorbent resin microspheres according to claim 1 or 2, characterized in that The resin seed microspheres are any one of polystyrene, polydivinylbenzene, polyacrylate or polyacrylonitrile; the particle size of the resin seed microspheres is 10 - 80 μm; The modifier containing a hydrophilic group is any one of polyvinyl alcohol, polyethylene glycol, β-cyclodextrin, nitrocellulose or phthalic anhydride.

4. The preparation method of the adsorbent resin microspheres according to claim 1 or 2, characterized in that The swelling is carried out in the presence of a swelling agent, and the swelling agent is one or a combination of two or more of dibutyl phthalate, toluene, 1-chlorododecane or N,N-dimethylformamide; The volume ratio of the resin seed microspheres to the swelling agent is 1:2 - 1:

7.

5. The preparation method of the adsorbent resin microspheres according to claim 2, characterized in that The volume ratio of the resin seed microspheres to the monomer is 1:9 - 1:20; The stabilizer is polyvinyl alcohol and / or hydroxyethyl cellulose; the addition amount of the stabilizer is 0.5 - 10% of the mass of the monomer; The initiator is one or a combination of two or more of benzoyl peroxide, azodiisobutyronitrile or tert-butyl peroxy-2-ethylhexanoate.

6. The preparation method of the adsorbent resin microspheres according to claim 1 or 2, characterized in that The conditions for polymerization are: the temperature is 60 - 75 °C; the polymerization time is 6 - 36 h.

7. The preparation method of the adsorbent resin microspheres according to claim 1 or 2, characterized in that After the polymerization reaction, it further includes a separation and purification step: the polymerization system is centrifuged and purified by solvent extraction; The solvent extraction is carried out by sequentially extracting with ethanol, acetone and purified water.

8. An adsorbent resin microsphere, characterized in that, The adsorbent microspheres are prepared by the preparation method of the adsorbent resin microspheres according to any one of claims 1 - 7.

9. The adsorbent resin microspheres according to claim 8, wherein The particle size of the adsorbent resin microspheres is 300 - 600 um.

10. The application of the adsorbent resin microspheres according to claim 9 in the field of blood purification.

Images