An adsorbent with double adsorption function, its preparation method and application

Abstract

The application provides an adsorbent with double adsorption effect and a preparation method and application thereof, and the preparation method comprises the following steps: preparing polystyrene-divinylbenzene macroporous resin; polystyrene-divinylbenzene macroporous resin and an acrylate monomer are subjected to polymerization reaction to obtain polystyrene-divinylbenzene / polyacrylate interpenetrating network resin; the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to chloromethylation reaction to obtain chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin; the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to alkylation reaction to obtain ultrahigh-crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin; and the ultrahigh-crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to aminolysis reaction to obtain the adsorbent. The adsorbent has double adsorption effect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of blood purification, in particular to an adsorbent with double adsorption effect and a preparation method and application thereof. BACKGROUND

[0002] Bilirubin is a product of heme metabolism degradation, and is an endogenous toxin. Under normal physiological conditions, serum proteins combine with bilirubin to help transfer bilirubin to the liver for excretion. When liver function is abnormal, bilirubin metabolism is impaired, resulting in accumulation of bilirubin in the blood. High concentration of bilirubin in the blood can cause obstructive jaundice, and even acute renal failure.

[0003] The level of bilirubin in the body is generally positively correlated with the degree of liver cell lesion. For patients with severe hepatitis or liver failure, their own ability to metabolize bilirubin is basically lost, and it is difficult to remove bilirubin in the body by general clinical treatment. Therefore, blood purification is often used to remove pathogenic substances. In addition, due to poor resistance of liver failure patients, many liver failure patients often accompany systemic inflammatory response syndrome and sepsis, which can seriously threaten the life and prognosis of patients. Therefore, it is necessary to develop a double plasma molecular adsorption system (DPMAS system) that can simultaneously remove bilirubin and cytokines.

[0004] The existing DPMAS system uses two adsorption columns simultaneously to adsorb and remove bilirubin and cytokines. Although good results can be achieved, the use of two adsorption columns simultaneously not only increases the use cost, but also increases the operation difficulty and the burden of medical staff. SUMMARY

[0005] The present application aims to solve the problem of high use cost and large operation difficulty caused by the need to use two adsorption columns for adsorption of bilirubin and cytokines in the prior art.

[0006] To solve the above problems, the first aspect of the present application provides a preparation method of an adsorbent with double adsorption effect, comprising the following steps:

[0007] Preparation of polystyrene-divinylbenzene macroporous resin by suspension polymerization reaction;

[0008] Polymerization reaction of the polystyrene-divinylbenzene macroporous resin and the acrylic ester monomer to obtain a polystyrene-divinylbenzene / polyacrylate interpenetrating network resin;

[0009] Chloromethylation of the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to obtain chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin;

[0010] alkylating the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to obtain a hypercrosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin;

[0011] subjecting the hypercrosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to an aminolysis reaction to graft amine anion exchange groups onto the polyacrylate to obtain an adsorbent with double adsorption effect.

[0012] Further, the polystyrene-divinylbenzene macroporous resin prepared by the suspension polymerization reaction comprises:

[0013] subjecting styrene monomers and polyvinyl crosslinking agents to a suspension polymerization reaction in a first dispersion medium under a first pore-forming agent and a first initiator to obtain the polystyrene-divinylbenzene macroporous resin, wherein the temperature of the suspension polymerization reaction is 50-100°C, and the reaction time is 12-20h.

[0014] Further, the polystyrene-divinylbenzene macroporous resin and the acrylate monomers are subjected to a polymerization reaction to obtain a polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, which comprises:

[0015] adding the polystyrene-divinylbenzene macroporous resin to a mixture of acrylate monomers, crosslinking agents, swelling agents, a second pore-forming agent and a second initiator to swell to obtain a swollen polystyrene-divinylbenzene macroporous resin, and subjecting the swollen polystyrene-divinylbenzene macroporous resin to a polymerization reaction in a second dispersion medium to obtain a polystyrene-divinylbenzene macroporous resin / polyacrylate interpenetrating network resin, wherein the temperature of the polymerization reaction is 45-80°C, and the reaction time is 12-20h.

[0016] Further, the acrylate monomers include at least one of methyl acrylate, ethyl acrylate, 2-methyl methyl acrylate, 2-methyl ethyl acrylate, ethylene glycol dimethyl acrylate, 1,4-butanediol diacrylate, pentaerythritol triacrylate and isocyanuric acid triallyl ester.

[0017] The swelling agent includes at least one of toluene, xylene, nitrobenzene and dichloroethane, and the mass of the swelling agent is 30-100% of the mass of the polystyrene-divinylbenzene macroporous resin.

[0018] Further, the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to a chloromethylation reaction to obtain a chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, which comprises:

[0019] The chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is obtained by adding chloromethyl ether to the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, standing for 4-5 hours at room temperature, and then adding anhydrous zinc chloride to perform a chloromethylation reaction, wherein the chloromethylation reaction is performed at a temperature of 40-50°C for 6-12 hours.

[0020] Further, the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to an alkylation reaction to obtain a super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, comprising:

[0021] The super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is obtained by adding nitrobenzene to the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, standing for 4-5 hours at 38-42°C, and then adding ferric chloride to perform an alkylation reaction, wherein the alkylation reaction is performed at a temperature of 70-90°C for 8-16 hours.

[0022] Further, the super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to an aminolysis reaction to graft amine anion exchange groups to the polyacrylate to obtain an adsorbent with double adsorption, comprising:

[0023] The adsorbent with double adsorption is obtained by adding an amine solution or a polyamine solution to the super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to perform an aminolysis reaction to graft amine anion exchange groups to the polyacrylate, wherein the aminolysis reaction is performed at a temperature of 80-100°C for 12-24 hours.

[0024] Further, the amine solution comprises an amine compound, and the mass fraction of the amine compound in the amine solution is 5-20%, and the amine compound comprises at least one of ethylenediamine, propylenediamine, butylenediamine, hexylenediamine, heptylenediamine, and octylenediamine;

[0025] The polyamine solution comprises a polyamine polymer, and the mass fraction of the polyamine polymer in the polyamine solution is 5-20%, and the polyamine polymer comprises at least one of triethylenetetramine, tetraethylenepentamine, pentaethylenehexamine, hexaethylenheptamine, polyethylene polyamine, and polyethyleneimine;

[0026] The mass ratio of the superhigh crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin and the amine solution is 1:4 to 1:6, and the mass ratio of the superhigh crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin and the polyamine solution is 1:4 to 1:6.

[0027] The second aspect of the present application provides a double-adsorption adsorbent prepared by the preparation method of the first aspect, wherein the specific surface area of the double-adsorption adsorbent ranges from 300 m 2 / g to 1200 m 2 / g, the pore volume ranges from 0.8 cm 3 / g to 2.0 cm 3 / g, the average pore size ranges from 2 nm to 20 nm, the particle size ranges from 0.2 mm to 1.8 mm, and the ion exchange capacity ranges from 0.1 mmol / g to 1.0 mmol / g.

[0028] The third aspect of the present application provides a hemoperfusion device comprising the double-adsorption adsorbent of the second aspect.

[0029] The adsorbent with double adsorption effect and the preparation method thereof, in the preparation process of macroporous adsorption resin, interpenetrating network polymer is introduced, polystyrene-divinylbenzene macroporous resin is used as the matrix, and the polyacrylate polymer obtained by polymerization of acrylate monomers is used as the interpenetrating polymer, so that the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin with hydrophobic network is prepared, then the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to chloromethylation reaction and alkylation reaction, so that the ultrahigh crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is prepared, which is beneficial to improving the specific surface area of the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin and the adsorption performance of the adsorbent, and the ultrahigh crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin can improve the stability and compatibility of the interpenetrating structure, which is beneficial to improving the strength of the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, finally, the polyacrylate in the ultrahigh crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is aminolysed into the polyacrylamide polymer with anion exchange effect and hydrophilicity, so that the adsorbent prepared finally not only retains the hydrophobic skeleton structure of polystyrene-divinylbenzene, but also has the polyacrylamide polymer, the polystyrene-divinylbenzene and the polyacrylamide polymer can not only coexist stably, but also do not interfere with each other, so that the adsorption and removal of the cytokine substances such as interleukin 6 can be realized through the hydrophobic skeleton structure and the pore structure of polystyrene-divinylbenzene, and the adsorption and removal of the substances such as bilirubin and bile acid can be realized through the polyacrylamide polymer, so that the adsorbent has the ability to remove bilirubin and cytokines at the same time, realizes the double adsorption effect of the adsorbent, and is beneficial to reducing the use cost and operation difficulty, providing convenience for medical staff and patients; in addition, the adsorbent has good stability and compatibility, which is beneficial to improving the use safety of the adsorbent, and the adsorbent is more suitable for application in the application field such as blood purification which has strict requirements on material stability and safety. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 The process flow chart for preparing the adsorbent with double adsorption effect is provided for the embodiments of the present application. DETAILED DESCRIPTION

[0031] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application are described in detail below with reference to the drawings.

[0032] It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict.

[0033] In addition, the terms "comprising", "including", "containing", "having" and their conjugates mean "including but not limited to" and permit also for example other steps, other ingredients and other components not expressly mentioned.

[0034] In addition, although the present application describes each step in the preparation in the form of S110, S120, etc., this description is only for the convenience of understanding and does not represent a limitation on the order of each step.

[0035] Figure 1 A process flow chart for preparing the adsorbent with double adsorption effect is provided in the embodiments of the present application. In combination with the description shown in the process flow chart, the embodiments of the present application provide a first aspect of a preparation method of the adsorbent with double adsorption effect, comprising the following steps: Figure 1 A process flow chart for preparing the adsorbent with double adsorption effect is provided in the embodiments of the present application. In combination with the description shown in the process flow chart, the embodiments of the present application provide a first aspect of a preparation method of the adsorbent with double adsorption effect, comprising the following steps:

[0036] Step S110: preparing polystyrene-divinylbenzene macroporous resin by a suspension polymerization reaction.

[0037] Specifically, the styrene monomer and the multi-vinyl crosslinking agent are subjected to a suspension polymerization reaction in the first dispersant under the first pore-forming agent and the first initiator, to obtain the polystyrene-divinylbenzene macroporous resin, wherein the temperature of the suspension polymerization reaction is 50-100°C, and the reaction time is 12-20h.

[0038] As a preferred embodiment, the suspension polymerization reaction is performed in a stepwise heating manner. Specifically, after the styrene monomer, the multi-vinyl crosslinking agent, the first pore-forming agent and the first initiator are uniformly mixed, the first dispersant is added, and after stirring to form uniform droplets, the temperature is raised to 73-77°C, the suspension polymerization reaction is performed for 3h, then the temperature is raised to 78-82°C for solidification for 7h, and then the temperature is raised to 83-87°C for solidification for 6h to stop the reaction. After the reaction product is sequentially washed with hot water, washed with acetone and dried, the polystyrene-divinylbenzene macroporous resin is obtained. In this way, the suspension polymerization reaction is performed in a stepwise heating manner, which can control the reaction speed and prevent the suspension polymerization reaction from being too violent, thereby affecting the quality of the polystyrene-divinylbenzene macroporous resin and thus affecting the adsorption effect of the finally prepared adsorbent.

[0039] The polystyrene-divinylbenzene macroporous resin prepared by the method of the present embodiment has a particle size range of 0.2-1.8mm, preferably a particle size range of 0.3-0.8mm.

[0040] As an optional embodiment, the styrene monomer is at least one of styrene, methylstyrene and ethylstyrene, preferably, the styrene monomer is styrene; the amount of the styrene monomer is 37% to 95% of the mass of the reaction monomer, wherein the reaction monomer refers to the styrene monomer and the multi-vinyl crosslinking agent, the mass of the reaction monomer is the sum of the mass of the styrene monomer and the mass of the multi-vinyl crosslinking agent, that is, the amount of the styrene monomer is 37% to 95% of the sum of the mass of the styrene monomer and the mass of the multi-vinyl crosslinking agent, and the same below, which will not be further explained. Thus, by selecting the above-mentioned substances as the styrene monomer and limiting the mass ratio of the styrene monomer and the reaction monomer in the above range, the crosslinking degree of the polystyrene-divinylbenzene macroporous resin can be adjusted so that the crosslinking degree of the polystyrene-divinylbenzene macroporous resin is in a suitable range.

[0041] As an optional embodiment, the multi-vinyl crosslinking agent is at least one of divinylbenzene, divinyltoluene, divinylxylene and divinyl ethylbenzene, preferably, the multi-vinyl crosslinking agent is divinylbenzene; the amount of the multi-vinyl crosslinking agent is 5% to 63% of the mass of the reaction monomer. Thus, by selecting the above-mentioned substances as the multi-vinyl crosslinking agent and limiting the mass ratio of the multi-vinyl crosslinking agent and the reaction monomer in the above range, the crosslinking degree of the polystyrene-divinylbenzene macroporous resin can be adjusted so that the crosslinking degree of the polystyrene-divinylbenzene macroporous resin is in a suitable range.

[0042] As an optional embodiment, the first pore-forming agent is at least one of aromatic hydrocarbons, alkanes, higher alcohols, higher ketones and esters, wherein the aromatic hydrocarbons are toluene or xylene; the alkanes are at least one of n-heptane, 200# gasoline and solid paraffin; the higher alcohols are at least one of butanol, hexanol, cyclohexanol, isooctanol, n-octanol and methyl isobutyl carbinol; the higher ketones are at least one of methyl isobutyl ketone, 2-hexanone, diisobutyl ketone and methyl tert-butyl ketone; and the esters are one of butyl acetate, ethyl acetate and butyl butyrate. The amount of the first pore-forming agent is 120% to 240% of the mass of the reaction monomer. Thus, by selecting the above-mentioned substances as the first pore-forming agent, the aromatic hydrocarbons are good solvents, the alkanes and the higher alcohols are poor solvents, and by adjusting the ratio of the good solvents and the poor solvents, the pore structure of the polystyrene-divinylbenzene macroporous resin can be adjusted so that the pore volume and the pore size of the polystyrene-divinylbenzene macroporous resin are adjusted.

[0043] As an optional embodiment, the first initiator is at least one of benzoyl peroxide, tert-butyl peroxy-2-ethylhexanoate, and tert-amyl peroxy-2-ethylhexanoate, preferably, the initiator is benzoyl peroxide, and the amount of the initiator is 0.5% to 1.5% of the mass of the reaction monomer. Thus, the above-mentioned substances are selected as the initiator, and the mass ratio of the initiator to the reaction monomer is limited in the above-mentioned range, which is beneficial to initiating the suspension polymerization reaction.

[0044] As an optional embodiment, the first dispersant is at least one of gelatin, polyvinyl alcohol, and hydroxymethyl cellulose, preferably, the dispersant is gelatin; the dispersion medium of the first dispersant is water, the amount of the water is 1 to 3 times of the total volume of the styrene monomer, the polyvinyl monomer crosslinking agent, the first pore-forming agent, and the first initiator, and the amount of the first dispersant is 0.5% to 2% of the mass of the dispersion medium.

[0045] In the embodiment, the polystyrene-divinylbenzene macroporous resin is prepared by the suspension polymerization reaction. The polystyrene-divinylbenzene macroporous resin has a hydrophobic polystyrene as a skeleton, and has better stability. The polystyrene-divinylbenzene macroporous resin has a large crosslinking density, high strength, and a rich pore structure. The pore structure is suitable in size, which is beneficial to increasing the specific surface area of the polystyrene-divinylbenzene macroporous resin and improving the adsorption capacity of the polystyrene-divinylbenzene macroporous resin. Through the hydrophobic interaction and the pore size screening of the polystyrene-divinylbenzene macroporous resin, the adsorption and removal of the cytokine substances such as interleukin 6 can be realized.

[0046] In step S120, the polystyrene-divinylbenzene macroporous resin and the acrylate monomer are subjected to a polymerization reaction to obtain a polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0047] Specifically, the polystyrene-divinylbenzene macroporous resin is added into a mixed solution of the acrylate monomer, the crosslinking agent, the swelling agent, the second pore-forming agent, and the second initiator, and is subjected to swelling. After swelling for 24 hours, the flowing solution is removed by suction filtration to obtain the swollen polystyrene-divinylbenzene macroporous resin. The swollen polystyrene-divinylbenzene macroporous resin is subjected to a polymerization reaction in a second dispersion medium to obtain a polystyrene-divinylbenzene macroporous resin / polyacrylate interpenetrating network resin. The temperature of the polymerization reaction is 45°C to 80°C, and the reaction time is 12 hours to 20 hours.

[0048] As a preferred embodiment, the polymerization reaction is performed in a stepwise temperature rising manner, specifically, the polystyrene-divinylbenzene macroporous resin is added into a mixed solution of the acrylate monomer, the crosslinking agent, the swelling agent, the second pore-forming agent and the second initiator, and is swelled to obtain the swelled polystyrene-divinylbenzene macroporous resin, the swelled polystyrene-divinylbenzene macroporous resin is heated to 63-67℃ in the second dispersion medium, and the polymerization reaction is performed for 2 hours, then heated to 73-77℃, and the polymerization reaction is performed for 2 hours, then heated to 83-87℃, and the polymerization reaction is performed for 2 hours, then heated to 93-97℃, and the reaction is stopped after 6 hours of temperature maintaining, the reaction product is washed with hot water, then washed with acetone, and then dried to obtain the polystyrene-divinylbenzene macroporous resin / polyacrylate interpenetrating network resin. In this way, the polystyrene-divinylbenzene macroporous resin is swelled and then polymerized, which can better enable the polyacrylate to interpenetrate in the polystyrene-divinylbenzene macroporous resin skeleton to form the polystyrene-divinylbenzene macroporous resin / polyacrylate interpenetrating network resin, and the polymerization reaction is performed in a stepwise temperature rising manner, which can control the reaction speed, prevent the polymerization reaction from being too violent, and affect the quality of the polystyrene-divinylbenzene macroporous resin / polyacrylate interpenetrating network resin, thereby affecting the adsorption effect of the finally prepared adsorbent.

[0049] As an optional embodiment, the acrylate monomer includes at least one of a mono-olefin monomer and a multi-olefin monomer, the mono-olefin monomer includes at least one of methyl acrylate, ethyl acrylate, 2-methyl methyl acrylate and 2-methyl ethyl acrylate, and the multi-olefin monomer includes at least one of ethylene glycol dimethacrylate, 1,4-butanediol diacrylate, pentaerythritol triacrylate and triallyl isocyanurate, preferably, the mono-olefin monomer includes methyl acrylate and 2-methyl methyl acrylate, and the multi-olefin monomer includes ethylene glycol dimethacrylate and triallyl isocyanurate; in this embodiment, the weight ratio of the multi-olefin monomer to the mono-olefin monomer is 10%-40%. In this way, the above-mentioned substances are selected as the acrylate monomer, which is conducive to forming the cross-interpenetrating polyacrylate on the polystyrene-divinylbenzene macroporous resin, thereby obtaining the polystyrene-divinylbenzene macroporous resin / polyacrylate interpenetrating network resin with both networks being hydrophobic.

[0050] As an optional embodiment, the swelling agent includes at least one of toluene, xylene, nitrobenzene and dichloroethane, preferably, the swelling agent is toluene; the mass of the swelling agent is 30%-100% of the mass of the polystyrene-divinylbenzene macroporous resin. In this way, the above-mentioned substances are selected as the swelling agent, which can sufficiently swell the polystyrene-divinylbenzene macroporous resin, so as to better enable the polyacrylate to interpenetrate in the polystyrene-divinylbenzene macroporous resin skeleton.

[0051] As an optional embodiment, the second pore-forming agent is at least one of esters, alkanes and higher alcohols, wherein the esters are one of butyl acetate, ethyl acetate and butyl butyrate; the alkanes are at least one of n-heptane and 200# gasoline; and the higher ketones are at least one of methyl isobutyl ketone, 2-hexanone, diisobutyl ketone and methyl tert-butyl ketone. The amount of the second pore-forming agent is 80% to 150% of the mass of the reaction monomers. Thus, the use of the above-mentioned substances as the second pore-forming agent is conducive to adjusting the pore structure of the polyacrylate, thereby adjusting the pore volume and pore size of the polyacrylate.

[0052] As an optional embodiment, the second initiator is at least one of benzoyl peroxide, tert-butyl peroxy-2-ethylhexanoate, tert-amyl peroxy-2-ethylhexanoate, azobis isobutyronitrile and azobis isohexylnitrile, preferably, the initiator is azobis isobutyronitrile and tert-butyl peroxy-2-ethylhexanoate, and the initiation temperature of these two substances is relatively low, which is more conducive to the occurrence of the polymerization reaction; the amount of the initiator is 0.5% to 1.5% of the mass of the acrylate monomers. Thus, the use of the above-mentioned substances as the initiator and the limitation of the mass ratio of the initiator to the acrylate monomers within the above-mentioned range are conducive to initiating the polymerization reaction.

[0053] As an optional embodiment, the second dispersing agent is at least one of gelatin, polyvinyl alcohol and hydroxymethyl cellulose, preferably, the second dispersing agent is polyvinyl alcohol; the dispersion medium of the second dispersing agent is an aqueous sodium chloride solution, and the amount of the aqueous sodium chloride solution is 1 to 3 times the volume of the oil phase; the polystyrene-divinylbenzene macroporous resin is added to the mixture of the acrylate monomers, the crosslinking agent, the swelling agent, the second pore-forming agent and the second initiator, and after swelling for 24 h, the remaining substance is the oil phase after removing the flowing solution by suction filtration; the amount of the second dispersing agent is 0.5% to 2% of the mass of the dispersion medium.

[0054] The specific type of the crosslinking agent is not further limited in the embodiment, and those skilled in the art can select the commonly used crosslinking agent in the art according to the actual situation. For example, a polyene monomer can be selected as the crosslinking agent in the embodiment, and the polyene monomer includes at least one of ethylene glycol dimethacrylate, 1,4-butanediol diacrylate, pentaerythritol triacrylate and isocyanuric acid triallyl ester.

[0055] In the embodiment, the polystyrene-divinylbenzene macroporous resin is used as the matrix, and the polyacrylate polymer obtained by polymerization of the acrylate monomers is used as the interpenetrating polymer, so that the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin with both networks being hydrophobic is prepared. The polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is used as the intermediate, which is conducive to the preparation of the adsorbent with double adsorption effect.

[0056] Step S130, chloromethylating the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to obtain a chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0057] Specifically, chloromethyl ether is added to the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, and after standing at room temperature for 4-5 hours, anhydrous zinc chloride is added to perform chloromethylation reaction, to obtain a chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, wherein the temperature of the chloromethylation reaction is 40-50°C, and the reaction time is 6-12 hours.

[0058] As an optional embodiment, the amount of chloromethyl ether added is 4-6 times the mass of the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin. In this way, the appropriate amount of chloromethyl ether is added, which is conducive to introducing an appropriate amount of chloromethyl groups into the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0059] In this embodiment, the chlorine content in the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is in the range of 5-15%. In this way, the chlorine content is limited within the above range, which is conducive to subsequent control of the crosslinking degree of the super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0060] As an optional embodiment, the amount of anhydrous zinc chloride added is 0.2-1 times the mass of the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin. In this way, the appropriate amount of anhydrous zinc chloride is added, which is conducive to catalyzing the chloromethylation reaction and improving the reaction rate.

[0061] In this embodiment, the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is obtained by chloromethylating the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, which is conducive to subsequent alkylation reaction to obtain a super-highly crosslinked resin.

[0062] Step S140, alkylation of the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to obtain a super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0063] Specifically, nitrobenzene is added to the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, and after standing for swelling at 38-42°C for 4-5 hours, iron chloride is added to perform alkylation reaction, to obtain a super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, wherein the temperature of the alkylation reaction is 70-90°C, and the reaction time is 8-16 hours.

[0064] As an optional embodiment, the amount of nitrobenzene added is 5 to 7 times the mass of the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin. By adding an appropriate amount of nitrobenzene, it is beneficial to convert the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin into a hyper-crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin after the alkylation reaction, avoiding the residual of the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0065] As an optional embodiment, the amount of ferric chloride added is 0.1 to 0.5 times the mass of the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin. By adding an appropriate amount of ferric chloride, it is beneficial to catalyze the alkylation reaction and improve the reaction rate.

[0066] In this embodiment, the hyper-crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is obtained by alkylation of the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, which is beneficial to increase the specific surface area of the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, thereby improving the adsorption performance of the finally prepared adsorbent. In addition, the hyper-crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin can improve the stability and compatibility of the interpenetrating structure, which is beneficial to improve the strength of the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0067] In step S150, the hyper-crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to an amination reaction to graft amine anion exchange groups to the polyacrylate, thereby obtaining an adsorbent with double adsorption effect.

[0068] Specifically, an amine solution or a polyamine solution is added to the hyper-crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, and the amination reaction is carried out under mechanical stirring and heating, so as to graft the amine anion exchange groups to the polyacrylate, thereby obtaining a hyper-crosslinked interpenetrating network resin with amine anion exchange groups grafted on the polyacrylate, i.e. an adsorbent with double adsorption effect. The temperature of the amination reaction is 80 to 100°C, and the reaction time is 12 to 24 hours.

[0069] As an optional embodiment, the amine solution comprises an amine compound, and the mass fraction of the amine compound in the amine solution is 5% to 20%; the amine compound comprises at least one of ethylenediamine, propylenediamine, butylenediamine, hexylenediamine, heptylenediamine and octylenediamine; the polyamine solution comprises a polyamine polymer, and the mass fraction of the polyamine polymer in the polyamine solution is 5% to 20%; the polyamine polymer comprises at least one of triethylenetetramine, tetraethylenepentamine, pentaethylenehexamine, hexaethylenheptamine, polyethylene polyamine and polyethyleneimine.

[0070] As an optional embodiment, the mass ratio of the super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to the amine solution is 1:4 to 1:6, and the mass ratio of the super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to the polyamine solution is 1:4 to 1:6. In this way, the appropriate amount of amine solution and polyamine solution can help to decompose the polyacrylate amine into hydrophilic and anion exchange functional polyacrylamide interpenetrating network polymer, and the appropriate amount of amine solution and polyamine solution can also provide a heat transfer medium for mechanical stirring.

[0071] In this embodiment, the polyacrylate amine is decomposed into hydrophilic and anion exchange functional polyacrylamide interpenetrating network polymer by the amine compound or the polyamine compound, and substances such as bilirubin and bile acid are adsorbed and removed by ion exchange effect, and the hydrophobic skeleton structure and pore structure of the super-high cross-linked polystyrene-divinylbenzene can realize the adsorption and removal of cytokine substances such as interleukin 6.

[0072] The preparation method of the adsorbent with double adsorption effect provided in the embodiment introduces interpenetrating network polymers in the preparation process of macroporous adsorption resin, takes polystyrene-divinylbenzene macroporous resin as a matrix, takes polyacrylate polymer obtained by polymerization of acrylate monomers as interpenetrating polymers, and prepares polystyrene-divinylbenzene / polyacrylate interpenetrating network resin with both networks being hydrophobic. Then, the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to chloromethylation reaction and alkylation reaction to prepare super-high crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, which is beneficial to increasing the specific surface area of the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin and improving the adsorption performance of the adsorbent. In addition, the super-high crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin can improve the stability and compatibility of the interpenetrating structure, which is beneficial to improving the strength of the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin. Finally, the polyacrylate in the super-high crosslinking polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is aminolysed into polyacrylamide polymer with anion exchange effect and hydrophilicity through aminolysis reaction. The adsorbent prepared finally not only retains the hydrophobic skeleton structure of polystyrene-divinylbenzene, but also has polyacrylamide polymer. The polystyrene-divinylbenzene and polyacrylamide polymer can not only stably coexist, but also do not interfere with each other, so that the adsorption and removal of cytokine substances such as interleukin 6 can be realized through the hydrophobic skeleton structure and pore structure of polystyrene-divinylbenzene, and the adsorption and removal of substances such as bilirubin and bile acid can be realized through polyacrylamide polymer, so that the adsorbent has the ability to remove bilirubin and cytokines at the same time, realizes the double adsorption effect of the adsorbent, and is beneficial to reducing the use cost and operation difficulty, providing convenience for medical staff and patients. In addition, the adsorbent provided in the embodiment has good stability and compatibility, which is beneficial to improving the use safety of the adsorbent, so that the adsorbent is more suitable for application in the application field of blood purification and other fields with strict requirements on material stability and safety.

[0073] The second aspect of the embodiment provides an adsorbent with double adsorption effect, which is prepared by the preparation method of the first aspect. The specific surface area of the adsorbent ranges from 300 m 2 / g to 1200 m 2 / g, the pore volume ranges from 0.8 cm 3 / g to 2.0 cm 3 / g, the average pore size ranges from 2 nm to 20 nm, the particle size ranges from 0.2 mm to 1.8 mm, and the ion exchange capacity ranges from 0.1 mmol / g to 1.0 mmol / g. Preferably, the specific surface area of the adsorbent ranges from 500 m 2 / g to 1000 m2 / g, the pore volume ranges from 1 cm 3 / g to 1.8 cm 3 / g, the average pore size ranges from 4 nm to 10 nm, the particle size ranges from 0.3 mm to 0.8 mm, and the ion exchange capacity ranges from 0.2 mmol / g to 0.6 mmol / g, wherein the mmol / g refers to the number of groups capable of ion exchange per gram of resin calculated by acid-base titration, for example: 0.2 mmol / g means that there are 0.2 mmol of groups capable of ion exchange per 1 g of adsorbent with double adsorption.

[0074] The third aspect of the embodiment provides a blood perfusion device, which comprises the adsorbent with double adsorption of the second aspect. The blood perfusion device provided by the embodiment can only comprise one adsorption column, and the blood perfusion device can solve the problems of bilirubin and cytokines of patients with liver failure, and is beneficial to reducing the use cost of the blood perfusion device.

[0075] In order to further illustrate the present application, the present application will be further illustrated by combining specific examples. The experimental methods used in the examples in the present application are all conventional methods unless otherwise specified; and the materials, reagents and the like used in the examples in the present application are all commercially available unless otherwise specified.

[0076] Example 1

[0077] The embodiment provides a preparation method of the adsorbent with double adsorption, which comprises the following steps:

[0078] (1) Preparation of polystyrene-divinylbenzene macroporous resin: 600 mL of 1.5 wt% gelatin aqueous solution, 43.6 g of styrene, 6.4 g of divinylbenzene (DVB) with a purity of 63 wt%, 30 g of toluene, 36 g of solid paraffin and 0.5 g of benzoyl peroxide are added into a 1000 mL three-necked flask to form a mixed organic phase, under mechanical stirring, the liquid droplets are stirred to be uniform in size, and then the temperature is raised to 75 DEG C for suspension polymerization for 3 h, then the temperature is raised to 80 DEG C for solidification for 7 h, then the temperature is raised to 85 DEG C for continuous solidification for 6 h, and then the reaction is stopped, and the reaction product is washed with hot water, washed with acetone and dried, and then sieved, and polystyrene-divinylbenzene macroporous resin with a particle size of 0.3 mm to 1.0 mm is selected.

[0079] (2) Preparation of polystyrene-divinylbenzene / polyacrylate interpenetrating network resin: 1000 mL of a three-necked flask was added 40 g of polystyrene-divinylbenzene macroporous resin obtained in step (1), and 24 g of methyl acrylate, 6 g of triallyl isocyanurate, 12 g of toluene, 30 g of butyl acetate, 15 g of n-heptane and 0.3 g of azobisisobutyronitrile were measured and added into the three-necked flask. After mixing uniformly, the mixture was stirred at room temperature for 24 h to swell, and then filtered to remove the solution that did not swell into the polystyrene-divinylbenzene macroporous resin. Then, 400 mL of an aqueous solution containing 1% polyvinyl alcohol and 5% sodium chloride was added, and the mixture was heated to 65°C under mechanical stirring to perform polymerization for 2 h. Then, the mixture was heated to 75°C to perform polymerization for 2 h, and then heated to 85°C to perform polymerization for 2 h. Then, the mixture was heated to 95°C to perform polymerization for 6 h, and then the reaction was stopped. After the reaction product was washed with hot water, eluted with acetone and dried, polystyrene-divinylbenzene / polyacrylate interpenetrating network resin was obtained.

[0080] (3) Preparation of chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin: 500 mL of a three-necked flask was added 20 g of polystyrene-divinylbenzene / polyacrylate interpenetrating network resin obtained in step (2), and 100 g of chloromethyl ether was added. After standing at room temperature for 4 h, a stirrer was started, and 10 g of anhydrous zinc chloride was added. The mixture was heated to 45°C to perform chloromethylation for 16 h. After the reaction was completed, the mixture was cooled to room temperature, and the mother liquor was filtered. The chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin was washed with methanol, filtered and dried. The content of chlorine in the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin was 10.6% as determined by the Volhard method.

[0081] (4) Preparation of super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin: 20 g of chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin obtained in step (3) was added to 140 g of nitrobenzene, and the mixture was swelled at 40°C for 4 h. Then, 4 g of ferric chloride was added under mechanical stirring, and the mixture was heated to 80°C to perform reaction for 8 h. The chloromethyl groups were subjected to a Friedel-Crafts alkylation reaction to form a super-highly crosslinked network. The number of micropores was greatly increased, and the stability and compatibility of the interpenetrating network structure were improved. Thus, super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin was obtained.

[0082] (5) Preparation of adsorbent having double adsorption: 20 g of super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin obtained in step (4) was added to 100 mL of an ethylenediamine aqueous solution having a mass fraction of 20%, and the mixture was heated to 100°C to perform aminolysis under mechanical stirring. The reaction was performed under reflux for 24 h. After the mixture was washed with pure water, super-highly crosslinked interpenetrating network resin having amine anion exchange groups grafted on the polyacrylate, i.e., adsorbent having double adsorption, was obtained.

[0083] The adsorbent with double adsorption prepared in the embodiment is a super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin with weak basic ion exchange capacity, which has a specific surface area of 910 m 2 / g, a pore volume of 1.6 cm 3 / g, an average pore size of 7.0 nm, and an ion exchange capacity of 0.22 mmol / g.

[0084] Example 2

[0085] The embodiment provides a preparation method of an adsorbent with double adsorption, which comprises the following steps.

[0086] (1) Preparation of polystyrene-divinylbenzene macroporous resin: 600 mL of 1.5 wt% gelatin aqueous solution, 38 g of styrene, 12 g of divinylbenzene (DVB) with a purity of 63 wt%, 20 g of toluene, 40 g of 200# gasoline, 20 g of n-octanol and 0.5 g of tert-butyl peroxy-2-ethylhexanoate are added into a 1000 mL three-necked flask, and then the mixture is stirred to form uniform liquid droplets, and then the temperature is raised to 75 °C for suspension polymerization for 3 h, and then the temperature is raised to 80 °C for solidification for 7 h, and then the temperature is raised to 85 °C for continuous solidification for 6 h, and then the reaction is stopped, and then the reaction product is washed with hot water, washed with acetone and dried, and then the polystyrene-divinylbenzene macroporous resin with a particle size of 0.3 mm to 1.0 mm is selected.

[0087] (2) Preparation of polystyrene-divinylbenzene / polyacrylate interpenetrating network resin: 40 g of polystyrene-divinylbenzene macroporous resin obtained in step (1) is added into a 1000 mL three-necked flask, 24 g of methyl acrylate, 6 g of ethylene glycol dimethyl acrylate, 18 g of toluene, 26 g of ethyl acetate, 18 g of methyl isobutyl ketone and 0.3 g of azobisisobutyronitrile are measured, and then the mixture is uniformly mixed and then added into the three-necked flask, and then the mixture is stirred at room temperature for 24 h for swelling, and then the mixture is filtered to remove the solution that is not swelled, and then 400 mL of an aqueous solution containing 1% polyvinyl alcohol and 5% sodium chloride is added, and then the temperature is raised to 65 °C for polymerization for 2 h, and then the temperature is raised to 75 °C for polymerization for 2 h, and then the temperature is raised to 85 °C for continuous polymerization for 2 h, and then the reaction is stopped, and then the temperature is raised to 95 °C for reaction for 6 h, and then the reaction is stopped, and then the reaction product is washed with hot water, washed with acetone and dried to obtain the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0088] (3) Preparation of chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin: 20 g of polystyrene-divinylbenzene / polyacrylate interpenetrating network resin obtained in step (2) above was added to a 500 mL three-necked flask, 100 g of chloromethyl ether was added, and the mixture was allowed to stand at room temperature for 4 h. Then, 10 g of anhydrous zinc chloride was added, and the mixture was heated to 45 °C and stirred for 16 h to perform the chloromethylation reaction. After the reaction was completed, the mixture was cooled to room temperature, and the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin was filtered off, washed with methanol, and then dried by suction filtration. The chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin was tested by the Volhard method, and the chlorine content was 9.5%.

[0089] (4) Preparation of super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin: 20 g of the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin obtained in step (3) was added to 140 g of nitrobenzene, and the mixture was allowed to stand at 40 °C for 4 h. Then, 4 g of ferric chloride was added, and the mixture was heated to 80 °C and stirred for 8 h to perform the Friedel-Crafts alkylation reaction of the chloromethyl group. The super-highly crosslinked network was formed, which greatly enriched the number of micropores and improved the stability and compatibility of the interpenetrating network structure. Thus, the super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin was obtained.

[0090] (5) Preparation of adsorbent with dual adsorption effect: 20 g of the super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin obtained in step (4) was added to 100 ml of a 10% triethylenetetramine aqueous solution, and the mixture was heated to 100 °C and stirred for 16 h to perform the amination reaction. After washing with pure water, the super-highly crosslinked interpenetrating network resin grafted with amine anion exchange groups on the polyacrylate was obtained, i.e., the adsorbent with dual adsorption effect.

[0091] The adsorbent with dual adsorption effect prepared in this example is a super-highly crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin with weak basic ion exchange capacity, which has a specific surface area of 740 m 2 / g, a pore volume of 1.5 cm 3 / g, and an average pore size of 8.1 nm, and an ion exchange capacity of 0.43 mmol / g.

[0092] Example 3

[0093] The present example provides a method for preparing an adsorbent with dual adsorption effect, which comprises the following steps:

[0094] (1) Preparation of polystyrene-divinylbenzene macroporous resin: 600 mL of 1.5 wt% gelatin aqueous solution was added into a 1000 mL three-necked flask, and a mixed organic phase containing 26 g of styrene, 24 g of divinylbenzene (DVB) with a purity of 63 wt%, 25 g of toluene, 25 g of solid paraffin, 30 g of methyl isobutyl ketone and 0.5 g of benzoyl peroxide was added. After stirring to form uniform droplets under mechanical stirring, the temperature was raised to 75°C for suspension polymerization for 3 h, then raised to 80°C for solidification for 7 h, and then raised to 85°C for further solidification for 6 h before stopping the reaction. The reaction product was washed with hot water, rinsed with acetone and dried, sieved, and polystyrene-divinylbenzene macroporous resin with a particle size of 0.3 mm to 1.0 mm was selected.

[0095] (2) Preparation of polystyrene-divinylbenzene / polyacrylate interpenetrating network resin: 40 g of polystyrene-divinylbenzene macroporous resin obtained in step (1) was added into a 1000 mL three-necked flask, and 24 g of 2-methyl methacrylate, 6 g of ethylene glycol dimethacrylate, 15 g of toluene, 36 g of butyl acetate, 15 g of n-heptane and 0.3 g of azobisisobutyronitrile were measured and uniformly mixed before being added into the three-necked flask. After swelling for 24 h at room temperature with stirring, the solution that did not swell was removed by suction filtration, and 400 mL of an aqueous solution containing 1% polyvinyl alcohol and 5% sodium chloride was added. The temperature was raised to 65°C for polymerization for 2 h, then raised to 75°C for polymerization for 2 h, and then raised to 85°C for polymerization for 2 h before stopping the reaction. The temperature was then raised to 95°C for reaction for 6 h before stopping the reaction. The reaction product was washed with hot water, rinsed with acetone and dried to obtain polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0096] (3) Preparation of chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin: 20 g of polystyrene-divinylbenzene / polyacrylate interpenetrating network resin obtained in step (2) above was added into a 500 mL three-necked flask, 100 g of chloromethyl ether was added, and the mixture was allowed to stand at room temperature for 4 h. The stirrer was then started, 10 g of anhydrous zinc chloride was added, and the temperature was raised to 45°C for chloromethylation for 12 h. After the reaction was completed, the temperature was cooled to room temperature, the mother liquor was filtered off, and the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin was washed with methanol, suction filtered and dried. The chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin was tested by the Volhard method, and the chlorine content was 8.7%.

[0097] (4) Preparation of super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin: 20 g of the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin obtained in step (3) was taken, 140 g of nitrobenzene was added, and the mixture was allowed to stand for swelling at 40°C for 4 h. Then, 4 g of ferric chloride was added under mechanical stirring, and the mixture was heated for reaction at 80°C for 8 h. The chloromethyl groups were subjected to a Friedel-Crafts alkylation reaction to form a super-high cross-linked network, which not only greatly enriched the number of micropores but also improved the stability and compatibility of the interpenetrating network structure, thereby obtaining a super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin.

[0098] (5) Preparation of adsorbent with dual adsorption effect: 20 g of the super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin obtained in step (4) was taken, 100 ml of a 20% by mass polyethylene polyamine aqueous solution was added, and the mixture was subjected to an amination reaction by heating to 100°C under mechanical stirring. After refluxing for 24 h, the mixture was washed with pure water to obtain a super-high cross-linked interpenetrating network resin having an amine anion exchange group grafted on the polyacrylate, i.e., an adsorbent with dual adsorption effect.

[0099] The adsorbent with dual adsorption effect obtained in this example is a super-high cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin having weak basic ion exchange capacity, which has a specific surface area of 680 m 2 / g, a pore volume of 1.3 cm 3 / g, and an average pore diameter of 7.6 nm, and an ion exchange capacity of 0.55 mmol / g.

[0100] The adsorbents with dual adsorption effect obtained in Examples 1 to 3 were used as blood perfusion adsorbents, and commercially available Zhuhai Jianfan BS resin and HA330-II resin were used as comparative examples. The plasma of a healthy person was added with bilirubin, bile acid, and interleukin 6 as simulated plasma of a patient with clinical liver failure. Each group of resins was subjected to adsorption at a bath ratio of 1:10 with respect to the plasma of the patient with liver failure, and the clearance effect of each group of resins on total bilirubin, total bile acid, and interleukin 6 was tested to obtain the results shown in Table 1.

[0101] Table 1

[0102] Group Total bilirubin Total bile acid Interleukin 6 Example 1 80.2％ 92.3％ 81.1％ Example 2 83.7％ 90.5％ 77.9％ Example 3 85.5％ 87.2％ 76.1％ Jianfan BS resin 65.2％ 68.1％ 5.5％ HA330-II resin 16.8％ 79.1％ 52.7％

[0103] As can be seen from Table 1, the adsorbents in Example 1 to Example 3 all have good removal effects on bilirubin, bile acid and interleukin 6, and the adsorption effects of the adsorbents in Example 1 to Example 3 are all superior to those of commercially available Jenapharm BS resin and HA330-II resin. It is thus illustrated that the adsorbent with double adsorption effect provided in the present application can simultaneously remove bilirubin and cytokines, and the adsorption capacity of the adsorbent on bilirubin and interleukin 6 both exceeds that of the existing BS resin and HA330-II resin for treating liver failure, and the adsorbent with double adsorption effect in the present application is expected to simultaneously solve the problems of bilirubin and cytokines of patients with liver failure through a single adsorbent and a single adsorption column, which is beneficial to reducing the use cost and operation difficulty, and provides convenience for medical staff and patients.

[0104] Although the present disclosure is disclosed as above, the protection scope of the present disclosure is not limited to this. Various changes and modifications can be made by those skilled in the art without departing from the spirit and scope of the present disclosure, and these changes and modifications shall fall within the protection scope of the present application.

Claims

1. A method for producing an adsorbent having a dual adsorption effect, characterized by, The method comprises the following steps: Preparation of polystyrene-divinylbenzene macroporous resin by suspension polymerization reaction; The polystyrene-divinylbenzene macroporous resin and the acrylate monomer are subjected to polymerization reaction to obtain polystyrene-divinylbenzene / polyacrylate interpenetrating network resin; The polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to chloromethylation reaction to obtain chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin; The chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to alkylation reaction to obtain ultrahigh-crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin; The ultrahigh-crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to aminolysis reaction, and an amine anion exchange group is grafted to the polyacrylate to obtain an adsorbent having double adsorption effect on bilirubin and cytokines; The ultrahigh-crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to aminolysis reaction, and an amine anion exchange group is grafted to the polyacrylate to obtain an adsorbent having double adsorption effect on bilirubin and cytokines; 2. The method for producing an adsorbent having a dual adsorption effect according to claim 1, characterized by, The ultrahigh-crosslinked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to aminolysis reaction, and an amine anion exchange group is grafted to the polyacrylate to obtain an adsorbent having double adsorption effect on bilirubin and cytokines; The method for preparing the adsorbent with double adsorption effect according to claim 3, wherein the acrylate monomer comprises at least one of methyl acrylate, ethyl acrylate, 2-methyl methyl acrylate, 2-methyl ethyl acrylate, ethylene glycol dimethyl acrylate, 1,4-butanediol diacrylate and pentaerythritol triacrylate; 3. The method for preparing the adsorbent having a dual adsorption effect according to claim 1, characterized by, The swelling agent comprises at least one of toluene, xylene, nitrobenzene and dichloroethane, and the mass of the swelling agent is 30% to 100% of the mass of the polystyrene-divinylbenzene macroporous resin. The polystyrene-divinylbenzene macroporous resin and the acrylate monomer are subjected to polymerization reaction to obtain polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, comprising: The polystyrene-divinylbenzene macroporous resin is added into a mixed solution of the acrylate monomer, a crosslinking agent, a swelling agent, a second pore-forming agent and a second initiator to swell to obtain swelled polystyrene-divinylbenzene macroporous resin, and the swelled polystyrene-divinylbenzene macroporous resin is subjected to polymerization reaction in a second dispersion medium to obtain polystyrene-divinylbenzene macroporous resin / polyacrylate interpenetrating network resin, wherein the temperature of the polymerization reaction is 45-80°C, and the reaction time is 12-20h.

4. The method for preparing the adsorbent with double adsorption effect according to claim 3, wherein the acrylate monomer comprises at least one of methyl acrylate, ethyl acrylate, 2-methyl methyl acrylate, 2-methyl ethyl acrylate, ethylene glycol dimethyl acrylate, 1,4-butanediol diacrylate and pentaerythritol triacrylate; The swelling agent comprises at least one of toluene, xylene, nitrobenzene and dichloroethane, and the mass of the swelling agent is 30% to 100% of the mass of the polystyrene-divinylbenzene macroporous resin.

5. The method for preparing the adsorbent with dual adsorption properties according to claim 1, characterized in that, The polystyrene-divinylbenzene macroporous resin and the acrylate monomer are subjected to polymerization reaction to obtain polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, comprising: The polystyrene-divinylbenzene macroporous resin and the acrylate monomer are subjected to polymerization reaction to obtain polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, comprising: Chloromethylation reaction is carried out by adding chloromethyl ether to the polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, adding anhydrous zinc chloride after standing at room temperature for 4h to 5h, to obtain chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, wherein the temperature of the chloromethylation reaction is 40℃ to 50℃, and the reaction time is 6h to 12h.

6. The method for preparing the adsorbent with dual adsorption properties according to claim 1, characterized in that, The chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to alkylation reaction to obtain ultrahigh cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, including: Ultrahigh cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is obtained by adding nitrobenzene to the chloromethylated polystyrene-divinylbenzene / polyacrylate interpenetrating network resin, adding ferric chloride after standing and swelling at 38℃ to 42℃ for 4h to 5h, and then carrying out alkylation reaction, wherein the temperature of the alkylation reaction is 70℃ to 90℃, and the reaction time is 8h to 16h.

7. The method for preparing the adsorbent with dual adsorption properties according to claim 1, characterized in that, The ultrahigh cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is subjected to aminolysis reaction to graft amine anion exchange groups to polyacrylate to obtain an adsorbent with dual adsorption effect on bilirubin and cytokines, including: The ultrahigh cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin is added to an amine solution to carry out aminolysis reaction to graft amine anion exchange groups to polyacrylate to obtain an adsorbent with dual adsorption effect on bilirubin and cytokines, wherein the temperature of the aminolysis reaction is 80℃ to 100℃, and the reaction time is 12h to 24h.

8. The preparation method of the adsorbent with dual adsorption effect according to claim 7, characterized in that, The amine solution contains amine compounds, and the mass fraction of the amine compounds in the amine solution is 5% to 20%, and the amine compounds include at least one of ethylenediamine, propylenediamine, butylenediamine, hexylenediamine, heptylenediamine and octylenediamine; The mass ratio of the ultrahigh cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to the amine solution is 1:4 to 1:

6.

9. The preparation method of the adsorbent with dual adsorption effect according to claim 7, characterized in that, The amine solution contains polyamine compounds, and the mass fraction of the polyamine compounds in the amine solution is 5% to 20%, and the polyamine compounds include at least one of triethylenetetramine, tetraethylenepentamine, pentaethylenehexamine, hexaethylenheptamine, polyethylene polyamine and polyethylene imine; The mass ratio of the ultrahigh cross-linked polystyrene-divinylbenzene / polyacrylate interpenetrating network resin to the amine solution is 1:4 to 1:

6.

10. An adsorbent having dual adsorption, characterized by, The adsorbent having a dual adsorption function has a specific surface area ranging from 300 m 2 / g to 1200 m 2 / g, a pore volume ranging from 0.8 cm 3 / g to 2.0 cm 3 / g, an average pore diameter ranging from 2 nm to 20 nm, a particle diameter ranging from 0.2 mm to 1.8 mm, and an ion exchange capacity ranging from 0.1 mmol / g to 1.0 mmol / g.

11. A hemocatheter, characterized by The adsorbent with dual adsorption effect according to claim 10 is included.

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