Adsorbent, preparation method thereof and hemoperfusion device

Abstract

The invention provides an adsorbent, a preparation method thereof and a blood perfusion device, the adsorbent takes chloromethyl-containing polystyrene-based macroporous resin as a carrier, adsorption ligands are immobilized, the adsorption ligands are MnO2 nanoparticles coated with chitosan, and the chitosan on the surfaces of the MnO2 nanoparticles reacts with chloromethyl to be immobilized on the carrier. The adsorbent provided by the invention can remove radioactive elements in a human body, and has the advantages of good blood compatibility, high safety and small side effect on the human body.

Description

Technical Field

[0001] The present invention relates to the technical field of blood purification, and in particular to an adsorbent and a preparation method thereof, and a blood perfusion device. Background Art

[0002] With the application of nuclear energy and nuclear technology in medical, scientific and production life, the amount of heavy metals and radioactive elements in wastewater and waste is increasing, which not only poses a serious threat to the environment, but these heavy metals and radioactive elements can also be transferred into the human body through the food chain, thereby increasing the probability of radiation damage to the human body.

[0003] In the prior art, radiation damage protection drugs or heavy metal chelators are mainly used to reduce the risk of radiation damage. However, the current radiation damage protection drugs are mainly sulfur-containing compounds, cytokines or hormone drugs. These drugs are mainly for hematopoietic and immune damage. They not only have a single effect and large side effects, but also have certain defects in efficacy and safety, which are difficult to meet clinical needs. Heavy metal chelators are mainly injected into the human body through intravenous injection, and the mechanism of action of chelators and heavy metal ions or radioactive elements to form soluble complexes is used to achieve clearance. However, this type of chelator has certain toxic side effects and may cause acute kidney poisoning and serious problems such as renal failure. Summary of the invention

[0004] The present invention aims to solve the above-mentioned defects of the prior art and provide an adsorbent capable of removing radioactive elements in the human body, the adsorbent having good blood compatibility, high safety and little side effect on the human body.

[0005] To solve the above problems, the first aspect of the present invention provides an adsorbent, which uses a polystyrene-based macroporous resin containing chloromethyl as a carrier and immobilizes an adsorption ligand, wherein the adsorption ligand is MnO2 nanoparticles coated with chitosan, and the chitosan on the surface of the MnO2 nanoparticle reacts with the chloromethyl group and is immobilized on the carrier.

[0006] The second aspect of the present invention provides a method for preparing an adsorbent, which is used to prepare the adsorbent as described in the first aspect, and the preparation method comprises the following steps:

[0007] Preparation of polystyrene-based macroporous resins containing chloromethyl groups;

[0008] Chitosan was grafted onto the surface of MnO2 nanoparticles to prepare chitosan-coated MnO2 nanoparticles;

[0009] Under alkaline conditions, the amino groups in the chitosan-coated MnO2 nanoparticles react with the chloromethyl groups in the polystyrene-based macroporous resin, and the chitosan-coated MnO2 nanoparticles are immobilized on the polystyrene-based macroporous resin to obtain the adsorbent.

[0010] The third aspect of the present invention provides a blood perfusion device, comprising the adsorbent as described in the first aspect, or comprising the adsorbent prepared by the preparation method as described in the second aspect.

[0011] The adsorbent of the present invention uses a polystyrene-based macroporous resin as a carrier, and immobilizes chitosan-coated MnO2 nanoparticles on the carrier. The MnO2 nanoparticles have a high specific surface area and surface activation energy, and can attract radioactive elements in the blood to the adsorption resin through van der Waals force and electrostatic binding, so as to quickly capture the radioactive elements in the blood. At the same time, the surface of the MnO2 nanoparticles contains abundant hydroxyl groups, which can combine with the radioactive elements to form hydroxyl complexes to adsorb the radioactive elements in the blood. Chitosan has good hydrophilicity and biocompatibility. By coating the surface of the MnO2 nanoparticles with chitosan, the radioactive elements in the blood can be adsorbed. Only the hydrophilicity and biocompatibility of MnO2 nanoparticles can be improved, the blood compatibility of MnO2 nanoparticles can be improved, and the hydroxyl group on the surface of chitosan can also be combined with radioactive elements to improve the adsorption of radioactive elements in blood, and polystyrene-based macroporous resin is used as a carrier, and polystyrene-based macroporous resin has abundant pore structure, which can physically adsorb radioactive elements, and the present invention combines the complexation of MnO2 nanoparticles and the physical adsorption of polystyrene-based macroporous resin by grafting the chitosan coated MnO2 nanoparticles on the surface of polystyrene-based macroporous resin, and adsorbs the radioactive elements in blood together, and can effectively remove the radioactive elements in blood. In addition, the chitosan on the surface of MnO2 nanoparticles is connected to the chloromethyl reaction on the polystyrene-based macroporous resin, and the MnO2 nanoparticles of chitosan coating can be firmly combined with the polystyrene-based macroporous resin, and the structural strength of the adsorbent is improved, and the adsorbent is not easy to be separated in the subsequent use process, and the use safety of the adsorbent is improved.

[0012] The preparation method of the adsorbent described in the present invention comprises the following steps: firstly preparing a polystyrene-based macroporous resin containing chloromethyl and chitosan-coated MnO2 nanoparticles respectively, and then immobilizing the chitosan-coated MnO2 nanoparticles on the polystyrene-based macroporous resin by reacting the amino groups in the chitosan-coated MnO2 nanoparticles with the chloromethyl groups in the polystyrene-based macroporous resin. The chitosan-coated MnO2 nanoparticles and the polystyrene-based macroporous resin can be tightly combined through chemical bond connection, thereby improving the structural strength and stability of the adsorbent. In addition, firstly preparing the polystyrene-based macroporous resin containing chloromethyl and then immobilizing the chitosan-coated MnO2 nanoparticles on the polystyrene-based macroporous resin can better regulate the pore structure and crosslinking degree of the polystyrene-based macroporous resin containing chloromethyl, and make the polystyrene-based macroporous resin have stronger physical adsorption. The adsorption capacity can also make the chitosan-coated MnO2 nanoparticles immobilized on the surface of the polystyrene-based macroporous resin, and the high specific surface area of ​​the polystyrene-based macroporous resin can be used to make the chitosan-coated MnO2 nanoparticles fully contact with the blood, avoiding the chitosan-coated MnO2 nanoparticles being loaded on the inner surface of the pores of the polystyrene-based macroporous resin, affecting the area of ​​the chitosan-coated MnO2 nanoparticles in contact with the blood, thereby affecting the adsorption effect of the adsorbent; in addition, compared with adding chitosan-coated MnO2 nanoparticles in the process of preparing a polystyrene-based macroporous resin containing chloromethyl, the preparation method of the adsorbent provided in this embodiment can avoid the chitosan-coated MnO2 nanoparticles being wrapped in the inside or inside of the polystyrene macroporous resin, affecting the adsorption capacity of the chitosan-coated MnO2 nanoparticles to radioactive elements. The preparation method of the adsorbent provided in this embodiment has a simple process flow, mild reaction conditions, and high safety during the reaction process, and is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 A process flow chart for preparing an adsorbent provided in an embodiment of the present invention;

[0014] Figure 2 A schematic diagram of the structure of a blood perfusion device provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0015] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0016] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments may be combined with each other.

[0017] In addition, the terms "comprising", "including", "containing", and "having" are not restrictive, that is, other steps and other components that do not affect the results can be added. Unless otherwise specified, materials, equipment, and reagents are commercially available.

[0018] In addition, although the present invention describes the steps in the preparation in the form of S110, S120, S130, etc., this description is only for ease of understanding, and the form of S110, S120, S130, etc. does not limit the sequence of the steps.

[0019] The first aspect of the embodiments of the present application provides an adsorption resin, which uses a polystyrene-based macroporous resin containing chloromethyl as a carrier and immobilizes an adsorption ligand, wherein the adsorption ligand is chitosan-coated MnO2 nanoparticles, and the chitosan on the surface of the MnO2 nanoparticles reacts with the chloromethyl group to be immobilized on the carrier.

[0020] The adsorption resin provided in the embodiment of the present application uses a polystyrene-based macroporous resin as a carrier, and immobilizes chitosan-coated MnO2 nanoparticles on the carrier. The MnO2 nanoparticles have a high specific surface area and surface activation energy, and can attract radioactive elements (such as uranium 235, strontium 90, rubidium 106 and cobalt 60, etc.) in the blood to approach the adsorption resin through van der Waals force and electrostatic binding, so as to quickly capture the radioactive elements in the blood. At the same time, the surface of the MnO2 nanoparticles contains abundant hydroxyl groups, which can combine with the radioactive elements to form hydroxyl complexes to adsorb the radioactive elements in the blood. Chitosan has good hydrophilicity and biocompatibility. 2. The surface coating chitosan of the nanoparticles can not only improve the hydrophilicity and biocompatibility of the MnO2 nanoparticles, but also improve the blood compatibility of the MnO2 nanoparticles. The hydroxyl groups on the surface of the chitosan can also combine with radioactive elements to improve the adsorption of radioactive elements in the blood. The polystyrene-based macroporous resin is used as a carrier. The polystyrene-based macroporous resin has a rich pore structure and can physically adsorb radioactive elements. The present embodiment combines the complexation of the chitosan-coated MnO2 nanoparticles grafted on the surface of the polystyrene-based macroporous resin with the physical adsorption of the polystyrene-based macroporous resin to jointly adsorb the radioactive elements in the blood, which can effectively remove the radioactive elements in the blood. In addition, the chitosan on the surface of the MnO2 nanoparticles is connected to the chloromethyl group on the polystyrene-based macroporous resin by reaction, so that the chitosan-coated MnO2 nanoparticles can be firmly combined with the polystyrene-based macroporous resin, thereby improving the structural strength of the adsorbent, making it difficult for the adsorbent to be separated in the subsequent use process, and improving the safety of the adsorbent.

[0021] On the basis of the above-described embodiment, as an optional implementation mode, the MnO2 nanoparticles of chitosan coating are formed by the reaction of MnO2 nanoparticles with polyoxyethylene grafted on the surface and chitosan, and polyoxyethylene is grafted on the surface of MnO2 nanoparticles by covalent bonds. Thus, by grafting polyoxyethylene on the surface of MnO2 nanoparticles, using polyoxyethylene as a connecting structure, it can react with chitosan, so that chitosan can be tightly connected to the surface of MnO2 nanoparticles by chemical bonds, not only improving the structural strength of the MnO2 nanoparticles of chitosan coating, avoiding the shedding phenomenon of chitosan or MnO2 nanoparticles, but also improving the hydrophilicity and biocompatibility of MnO2 nanoparticles. In addition, chitosan can also react with bacteria in blood by coating chitosan on the surface of MnO2 nanoparticles, thereby playing an antibacterial effect.

[0022] On the basis of the above embodiment, as an optional implementation mode, in the adsorption ligand, the mass ratio of MnO2 nanoparticles to polystyrene-based macroporous resin containing chloromethyl group is 0.01:1 to 0.3:1, and the mass ratio of chitosan to polystyrene-based macroporous resin containing chloromethyl group is 0.2:1 to 0.4:1. Thus, by limiting the mass ratio of MnO2 nanoparticles to polystyrene-based macroporous resin containing chloromethyl group and the mass ratio of chitosan to polystyrene-based macroporous resin containing chloromethyl group, the MnO2 nanoparticles can have good hydrophilicity and biocompatibility, improve the blood compatibility of the MnO2 nanoparticles, and the chitosan-coated MnO2 nanoparticles can have better adsorption performance for radioactive elements in the blood.

[0023] In this embodiment, the particle size of the MnO2 nanoparticles is 30nm to 100nm, the pore size is 2nm to 10nm, and the specific surface area is 200m 2 / g to 400m 2 Of course, those skilled in the art can also adjust the particle size, pore size and specific surface area of ​​the MnO2 nanoparticles according to actual conditions.

[0024] Figure 1 The process flow chart of preparing the adsorbent provided in the examples of this application. Figure 1 As shown, the second aspect of the embodiment of the present application provides a method for preparing an adsorbent, which is used to prepare the adsorbent as described in the first aspect, and the preparation method comprises the following steps:

[0025] Step S110, preparing a polystyrene-based macroporous resin containing chloromethyl groups.

[0026] Specifically, styrene and divinylbenzene are subjected to suspension polymerization reaction to obtain polystyrene-based macroporous resin, and the polystyrene-based macroporous resin and chloromethyl ether are subjected to chloromethylation reaction under the action of a catalyst to obtain polystyrene-based macroporous resin containing chloromethyl.

[0027] Based on the above embodiment, as an optional implementation, styrene and divinylbenzene are subjected to suspension polymerization to prepare a polystyrene-based macroporous resin, comprising the following steps:

[0028] The polystyrene-based macroporous resin is prepared by suspension polymerization of styrene monomers, polyvinyl crosslinking agents, porogens and initiators in a dispersion medium. Specifically, the styrene-based monomers, polyvinyl crosslinking agents, porogens and initiators are mixed to form an oil phase, the oil phase is added to the dispersion medium, and the suspension polymerization reaction is carried out at 50°C to 100°C under stirring. After the reaction is carried out for 12h to 20h, the suspension polymerization product is cleaned and dried to obtain the polystyrene-based macroporous resin. Preferably, the suspension polymerization reaction temperature is 70°C to 95°C, and the reaction time is 14h to 18h.

[0029] When carrying out suspension polymerization, the temperature can be gradually increased in stages. For example, after the oil phase forms uniform droplets of a certain size in the dispersion medium, the temperature can be increased to 75°C for polymerization for 3 hours, then increased to 80°C for reaction for 7 hours, and then increased to 85°C for reaction for 6 hours before stopping the reaction.

[0030] Wherein, the styrene monomer is selected from at least one of styrene, methyl styrene, and ethyl styrene, preferably, the styrene monomer is styrene; the polyvinyl crosslinking agent is selected from at least one of divinylbenzene, divinyltoluene, divinylxylene, and divinylethylbenzene, preferably, the polyvinyl crosslinking agent is divinylbenzene. The styrene monomer accounts for 20% to 92% of the total mass of the styrene monomer and the polyvinyl crosslinking agent, and the polyvinyl crosslinking agent accounts for 8% to 80% of the total mass of the styrene monomer and the polyvinyl crosslinking agent. Therefore, by using monovinyl styrene monomers and polyvinyl crosslinking agents as reaction monomers, the polystyrene-based macroporous resin is partially crosslinked, which is beneficial to improve the mechanical strength of the polystyrene-based macroporous resin and the structural stability in organic solvents.

[0031] The porogen is a mixture of at least two substances selected from aromatic hydrocarbons, alkanes, higher alcohols, higher ketones, and esters; wherein the aromatic hydrocarbons are selected from toluene and xylene; the alkanes are selected from n-heptane, 200# gasoline, and solid paraffin; the higher alcohols are selected from butanol, hexanol, cyclohexanol, isooctyl alcohol, n-octanol, and methyl isobutyl carbinol; the higher ketones are selected from methyl isobutyl ketone, 2-hexanone, diisobutyl ketone, and methyl tert-butyl ketone; and the esters are selected from butyl acetate, ethyl acetate, and butyl butyrate. As an optional embodiment, the mass of the porogen can be 70% to 230% of the total mass of the styrene monomer and the polyvinyl crosslinking agent.

[0032] The initiator is selected from at least one of benzoyl peroxide, tert-butyl peroxy-2-ethylhexanoate, and tert-amyl peroxy-2-ethylhexanoate. Preferably, the initiator is benzoyl peroxide. As an optional embodiment, the mass of the initiator is 0.5% to 1.5% of the total mass of the styrene monomer and the polyvinyl crosslinking agent. Therefore, the use of the above initiator can effectively initiate polymerization, and the price of the initiator is relatively low.

[0033] The dispersion medium is water, and the volume ratio of the dispersion medium to the oil phase is 1:1 to 3:1. The dispersion medium contains a dispersant, which is selected from at least one of gelatin, polyvinyl alcohol, and carboxymethyl cellulose. Preferably, the dispersion medium is gelatin. As an optional embodiment, the mass of the dispersant is 0.5% to 2% of the mass of the dispersion medium. Therefore, the use of the above dispersion medium is safe and environmentally friendly, and can achieve suspension polymerization of polystyrene-based macroporous resin.

[0034] In this embodiment, the particle size of the polystyrene-based macroporous resin may range from 0.2 mm to 1 mm. Preferably, the particle size of the polystyrene-based macroporous resin ranges from 0.3 mm to 0.6 mm.

[0035] Based on the above embodiment, as an optional implementation mode, a polystyrene-based macroporous resin and chloromethyl ether are subjected to a chloromethylation reaction under the action of a catalyst to prepare a polystyrene-based macroporous resin containing chloromethyl groups, comprising the following steps:

[0036] After the polystyrene-based macroporous resin and chloromethyl ether are mixed, they are allowed to stand at room temperature for 4 to 5 hours, and then anhydrous zinc chloride is added under stirring, and the reaction is carried out at 50°C to 52°C for 8 to 24 hours to obtain a polystyrene-based macroporous resin containing chloromethyl. Wherein, the mass of chloromethyl ether is 4 to 6 times the mass of the polystyrene-based macroporous resin, and the mass of anhydrous zinc chloride is 0.5 to 1.5 times the mass of the polystyrene-based macroporous resin. Thus, the amount ratio of each substance is limited within the above range, and the above reaction conditions are adopted to ensure that a sufficient amount of chloromethyl is introduced, so that the subsequent chloromethyl reacts with the amino group in the chitosan-coated MnO2 nanoparticles to immobilize the chitosan-coated MnO2 nanoparticles on the polystyrene-based macroporous resin. In this embodiment, the chlorine content in the polystyrene-based macroporous resin is not further limited. For example, the chlorine content in the polystyrene-based macroporous resin can be 5% to 25%.

[0037] The polystyrene-based macroporous resin prepared by the above method has two pore structures, namely, rich mesopores and micropores, and the polystyrene-based macroporous resin has an ultra-high specific surface area, which makes it have excellent physical adsorption capacity, and can improve the removal rate of radioactive elements through physical adsorption; in this embodiment, by introducing chloromethyl groups on the polystyrene-based macroporous resin, not only can the chitosan-coated MnO2 nanoparticles be immobilized on the polystyrene-based macroporous resin, but also the chloromethylation of the polystyrene-based macroporous resin can perform secondary cross-linking on the polystyrene-based macroporous resin, which is beneficial to improve the cross-linking degree of the polystyrene-based macroporous resin, improve the mechanical properties, structural strength and stability of the carrier, and also help to enrich the number of micropores, which is beneficial to further improve the adsorption capacity of the carrier.

[0038] Step S120, grafting chitosan onto the surface of MnO2 nanoparticles to obtain chitosan-coated MnO2 nanoparticles.

[0039] Specifically, MnO2 nanoparticles, aminosilane coupling agent and grafting compound are reacted, and the grafting compound is grafted to the surface of MnO2 nanoparticles through covalent bonds to obtain activated MnO2 nanoparticles; the activated MnO2 nanoparticles are reacted with chitosan, and chitosan is grafted to the polyethylene oxide on the surface of the activated MnO2 nanoparticles to obtain chitosan-coated MnO2 nanoparticles; wherein the grafting compound is a compound containing polyethylene oxide.

[0040] Based on the above embodiment, as an optional implementation, MnO2 nanoparticles, an aminosilane coupling agent and a grafting compound are reacted, and the grafting compound is grafted to the surface of the MnO2 nanoparticles through covalent bonds to obtain activated MnO2 nanoparticles, comprising the following steps:

[0041] The MnO2 nanoparticles are dispersed in a chloroform solution, an aminosilane coupling agent is added to the chloroform solution, and the solution is stirred and reacted at 45°C to 55°C for 8h to 12h, and then an excess of a grafting compound is added, and the solution is heated to 50°C to 60°C and stirred and reacted for 8h to 12h to graft the grafting compound to the surface of the MnO2 nanoparticles through covalent bonds.

[0042] In this embodiment, the surface of the MnO2 nanoparticles is first treated with an aminosilane coupling agent to aminize the surface of the MnO2 nanoparticles, and then an excess of a grafting compound (i.e., a compound containing polyoxyethylene) is added to cause the polyoxyethylene to be covalently grafted onto the surface of the MnO2 nanoparticles through a Michael addition reaction between the double bonds in the grafting compound and the amino groups on the surface of the MnO2 nanoparticles. Thus, the surface of the MnO2 nanoparticles can be organically treated by grafting the grafting compound onto the surface of the MnO2 nanoparticles, which is beneficial for the subsequent encapsulation of chitosan onto the surface of the MnO2 nanoparticles, thereby improving the surface properties of the MnO2 nanoparticles.

[0043] Based on the above embodiment, as an optional implementation, the compound containing polyoxyethylene can be polyoxyethylene methacrylate or polyoxyethylene acrylate.

[0044] Based on the above embodiment, as an optional embodiment, the aminosilane coupling agent can be KH-550 (γ-aminopropyl triethoxysilane) or KH-580 (γ-mercaptopropyl triethoxysilane). Of course, the aminosilane coupling agent can also be other types of aminosilane coupling agents. In this embodiment, the amount of aminosilane coupling agent added is 0.2% to 2% of the mass of the MnO2 nanoparticles, which is conducive to improving the reactivity of the surface of the MnO2 nanoparticles.

[0045] Based on the above embodiment, as an optional implementation, the mass ratio of MnO2 nanoparticles to polystyrene-based macroporous resin containing chloromethyl is 0.01:1 to 0.3:1, thereby enabling the adsorbent to have better adsorption performance for radioactive elements in blood. In this embodiment, the amount of the grafted compound added is not further limited, as long as the amount of the grafted compound added is ensured to be in excess of the amount of the MnO2 nanoparticles.

[0046] Based on the above embodiment, as an optional implementation, the activated MnO2 nanoparticles are reacted with chitosan, and the chitosan is grafted onto the polyethylene oxide on the surface of the activated MnO2 nanoparticles, comprising the following steps:

[0047] Under acidic conditions, activated MnO2 nanoparticles and chitosan are added to a buffer solution, and ammonium cerium nitrate is used as an initiator. The reaction is stirred at 40°C to 50°C for 8h to 12h to graft chitosan onto the polyethylene oxide on the surface of the activated MnO2 nanoparticles.

[0048] In this embodiment, the surface of the activated MnO2 nanoparticles is grafted with polyethylene oxide. Under the action of the oxidant ammonium cerium nitrate, the polyethylene oxide can be chemically bonded to the hydroxyl groups on the surface of chitosan, so that the chitosan can be coated on the surface of the activated MnO2 nanoparticles, which not only improves the hydrophilicity and biocompatibility of the MnO2 nanoparticles, but also improves the structural strength of the chitosan-coated MnO2 nanoparticles. In addition, the chitosan surface is rich in hydroxyl groups. After being connected with polyethylene oxide, the residual hydroxyl groups have strong activity and can be combined with radioactive elements through complexation, which is beneficial to further improve the adsorption of radioactive elements in the blood.

[0049] Based on the above embodiment, as an optional implementation, the mass ratio of chitosan to polystyrene-based macroporous resin containing chloromethyl is 0.2:1 to 0.4:1, that is, the amount of chitosan added is 20% to 40% of the mass of polystyrene-based macroporous resin containing chloromethyl. Thus, the MnO2 nanoparticles can have better hydrophilicity and biocompatibility, and the blood compatibility of the MnO2 nanoparticles is improved.

[0050] Based on the above embodiment, as an optional implementation, the mass ratio of ammonium cerium nitrate to activated MnO2 nanoparticles is 1: 100 to 3: 100. Thus, by limiting the amount of ammonium cerium nitrate within the above range, it is possible to ensure that the reaction between the activated MnO2 nanoparticles and chitosan is initiated, and it is also possible to ensure that the ammonium cerium nitrate undergoes a sufficient oxidation reaction, so that the activated MnO2 nanoparticles and chitosan are combined together through chemical bonds.

[0051] Based on the above embodiment, as an optional implementation, the acidic condition refers to an acidic condition with a pH value of 4 to 6. Therefore, carrying out the reaction within this pH value range is conducive to improving the oxidizability of ammonium cerium nitrate, making it have strong oxidizability, thereby helping to improve the activity of the oxidation reaction.

[0052] Based on the above embodiment, as an optional implementation, the buffer solution can be Tris-HCL buffer.

[0053] After chitosan is grafted onto the polyethylene oxide on the surface of the activated MnO2 nanoparticles, chitosan-coated MnO2 nanoparticles are obtained. The chitosan-coated MnO2 nanoparticles are first washed with a sodium bicarbonate solution and then washed with purified water until neutral to remove the acidic solution remaining in the chitosan-coated MnO2 nanoparticles and set aside to avoid affecting the activity of subsequent reactions.

[0054] Step S130: Under alkaline conditions, the amino groups in the chitosan-coated MnO2 nanoparticles react with the chloromethyl groups in the polystyrene-based macroporous resin to immobilize the chitosan-coated MnO2 nanoparticles on the polystyrene-based macroporous resin to obtain an adsorbent.

[0055] Specifically, under alkaline conditions, chitosan-coated MnO2 nanoparticles are mixed with polystyrene-based macroporous resin, and DMAP (4-dimethylaminopyridine) is used as a catalyst. The reaction is stirred at 70°C to 80°C for 8h to 12h to immobilize the chitosan-coated MnO2 nanoparticles on the polystyrene-based macroporous resin.

[0056] The surface of chitosan contains not only abundant hydroxyl groups but also active amino groups. After the MnO2 nanoparticles are coated by chitosan, the surface of the chitosan-coated MnO2 nanoparticles has both abundant hydroxyl groups and active amino groups. Under the action of the catalyst, the active amino groups react with the chloromethyl groups on the polystyrene-based macroporous resin to immobilize the chitosan-coated MnO2 nanoparticles on the polystyrene-based macroporous resin. The two are tightly connected, and the chitosan-coated MnO2 nanoparticles are loaded on the surface of the polystyrene-based macroporous resin and can directly contact the blood, which is beneficial to the adsorption of radioactive elements in the blood.

[0057] Based on the above embodiment, as an optional implementation, the mass ratio of DMAP to the polystyrene-based macroporous resin containing chloromethyl groups is 1: 100 to 5: 100. Therefore, limiting the amount of DMAP to the above range is conducive to increasing the reaction rate of amino groups and chloromethyl groups and improving the efficiency of preparing the adsorbent.

[0058] Based on the above examples, as an optional implementation, the alkaline condition refers to an alkaline condition with a pH value of 8 to 10. Therefore, when the reaction is carried out within this pH range, the amino groups on the surface of chitosan have strong reactivity, and the amino groups have strong nucleophilicity, which is conducive to improving the reactivity of the amino groups with the chloromethyl groups.

[0059] The preparation method of the adsorbent provided in the embodiment of the present application comprises the following steps: firstly preparing a polystyrene-based macroporous resin containing chloromethyl and chitosan-coated MnO2 nanoparticles respectively, and then immobilizing the chitosan-coated MnO2 nanoparticles on the polystyrene-based macroporous resin by reacting the amino groups in the chitosan-coated MnO2 nanoparticles with the chloromethyl groups in the polystyrene-based macroporous resin. The chitosan-coated MnO2 nanoparticles and the polystyrene-based macroporous resin can be tightly combined through chemical bond connection, thereby improving the structural strength and stability of the adsorbent. In addition, firstly preparing a polystyrene-based macroporous resin containing chloromethyl and then immobilizing the chitosan-coated MnO2 nanoparticles on the polystyrene-based macroporous resin can better regulate the pore structure and crosslinking degree of the polystyrene-based macroporous resin containing chloromethyl, and make the polystyrene-based macroporous resin have stronger physical and chemical properties. The adsorption capacity of the adsorbent can be improved, and the chitosan-coated MnO2 nanoparticles can be immobilized on the surface of the polystyrene-based macroporous resin, and the high specific surface area of ​​the polystyrene-based macroporous resin can be used to make the chitosan-coated MnO2 nanoparticles fully contact with the blood, avoiding the chitosan-coated MnO2 nanoparticles being loaded on the inner surface of the pores of the polystyrene-based macroporous resin, affecting the area of ​​the chitosan-coated MnO2 nanoparticles in contact with the blood, thereby affecting the adsorption effect of the adsorbent; in addition, compared with adding chitosan-coated MnO2 nanoparticles in the process of preparing a polystyrene-based macroporous resin containing chloromethyl, the preparation method of the adsorbent provided in this embodiment can avoid the chitosan-coated MnO2 nanoparticles being wrapped inside or on the inside of the polystyrene macroporous resin, affecting the adsorption capacity of the chitosan-coated MnO2 nanoparticles for radioactive elements. The preparation method of the adsorbent provided in this embodiment has a simple process flow, mild reaction conditions, and high safety during the reaction process, and is suitable for industrial production.

[0060] Figure 2 FIG. 1 is a schematic diagram of the structure of a blood perfusion device provided in an embodiment of the present application. Figure 2 As shown, the third aspect of the embodiment of the present application provides a blood perfusion device, which includes the adsorbent described in the first aspect of the present application, or includes the adsorbent prepared by the preparation method described in the second aspect of the present application. Figure 2 As shown, during blood purification, blood enters from the inlet 1, passes through the filter frame 2 and contacts the adsorbent 3 inside the blood perfusion device. The adsorbent 3 adsorbs the radioactive elements in the blood, and then the blood is discharged from the outlet 4, completing the blood purification process.

[0061] The blood perfusion device in the embodiment of the present application can draw the patient's blood out of the body for adsorption, and can absorb the radioactive elements in the patient's body in a short time to relieve the patient's pain. Using the blood perfusion device to absorb the radioactive elements in the patient's body is not only time-saving, but also highly safe and has little side effects on the human body.

[0062] In order to further explain the present invention in detail, the present invention will be further explained in conjunction with specific examples. The experimental methods used in the examples of the present invention are conventional methods unless otherwise specified; the materials, reagents, etc. used in the examples of the present invention are purchased from the market unless otherwise specified.

[0063] Example 1

[0064] This embodiment provides a method for preparing an adsorbent, comprising the following steps:

[0065] (1) In a 1000 mL three-necked flask, add 600 mL of a 1.5 wt% gelatin aqueous solution, 42 g of styrene, 8 g of divinylbenzene (DVB) with a purity of 63 wt%, 35 g of toluene, 20 g of 200# gasoline, 10 g of solid paraffin, and 0.5 g of benzoyl peroxide to form an oil phase, slowly add the oil phase to the gelatin aqueous solution, raise the temperature to 75°C for reaction for 5 h under mechanical stirring, and then raise the temperature to 80°C for reaction overnight. After the reaction is completed, cool, extract with acetone for 12 h, wash with water until there is no acetone smell, filter, dry, and sieve to select a resin with a particle size of 0.3 mm to 0.6 mm, thereby obtaining a polystyrene-based macroporous resin. In a 500mL three-necked flask, add 20g of polystyrene-based macroporous resin and 100g of chloromethyl ether, and let stand at room temperature for 4h; start the stirrer, add 20g of anhydrous zinc chloride, raise the temperature to 50℃ and react for 24h. After the reaction is completed, cool to room temperature, filter out the mother liquor, extract with methanol for 12h, wash with water until there is no methanol smell, filter, and dry to obtain a polystyrene-based macroporous resin containing chloromethyl.

[0066] (2) MnO2 nanoparticles were weighed according to a mass ratio of MnO2 nanoparticles to polystyrene-based macroporous resin containing chloromethyl group of 0.1:1, and the MnO2 nanoparticles were dispersed in a chloroform solution. An aminosilane coupling agent KH-550 was added to the chloroform solution in an amount of 1% of the mass of the MnO2 nanoparticles. The solution was heated to 50°C and stirred for reaction for 8 hours, and then an excess amount of polyoxyethylene methacrylate was added. The solution was heated to 60°C and stirred for reaction for 8 hours to prepare To obtain activated MnO2 nanoparticles; under the condition of pH 5, add activated MnO2 nanoparticles and ammonium cerium nitrate to Tris-HCL buffer solution, the mass ratio of ammonium cerium nitrate to activated MnO2 nanoparticles is 1:100, then add chitosan to the Tris-HCL buffer solution, the amount of chitosan added is 30% of the mass of the polystyrene-based macroporous resin containing chloromethyl, heat to 45°C and stir to react for 12 hours, after sufficient reaction, obtain chitosan-coated MnO2 nanoparticles.

[0067] (3) Under the condition of pH 9, the chitosan-coated MnO2 nanoparticles prepared in step (2) are mixed with the polystyrene-based macroporous resin prepared in step (1), and a catalyst DMAP is added, wherein the mass ratio of the added amount of DMAP to the polystyrene-based macroporous resin prepared in step (1) is 1:100. The mixture is heated to 80° C., stirred for reaction for 12 h, cooled to room temperature, filtered, washed and dried to obtain an adsorbent.

[0068] The adsorbent in this embodiment is used to adsorb the plasma solution containing radioactive elements. The adsorbent is effective for Sr 2+ The adsorption rate of Co 2+ The adsorption rate of U 4+ The adsorption rate is 98.8%.

[0069] Example 2

[0070] This embodiment provides a method for preparing an adsorbent, comprising the following steps:

[0071] (1) A polystyrene-based macroporous resin containing chloromethyl groups was prepared in the same manner as in Example 1.

[0072] (2) MnO2 nanoparticles were weighed according to a mass ratio of MnO2 nanoparticles to polystyrene-based macroporous resin containing chloromethyl group of 0.2:1, and the MnO2 nanoparticles were dispersed in a chloroform solution. An aminosilane coupling agent KH-550 was added to the chloroform solution in an amount of 1.5% of the mass of the MnO2 nanoparticles. The solution was heated to 50°C and stirred for reaction for 8 hours, and then an excess amount of polyoxyethylene methacrylate was added. The solution was heated to 60°C and stirred for reaction for 8 hours. Activated MnO2 nanoparticles were prepared; under the condition of pH 5, activated MnO2 nanoparticles and ammonium cerium nitrate were added to a Tris-HCL buffer solution, the mass ratio of ammonium cerium nitrate to activated MnO2 nanoparticles was 1:100, chitosan was then added to the Tris-HCL buffer solution, the amount of chitosan added was 40% of the mass of the polystyrene-based macroporous resin containing chloromethyl, the solution was heated to 45°C and stirred for reaction for 12 hours, and after sufficient reaction, chitosan-coated MnO2 nanoparticles were obtained.

[0073] (3) Under the condition of pH 9, the chitosan-coated MnO2 nanoparticles prepared in step (2) are mixed with the polystyrene-based macroporous resin prepared in step (1), and a catalyst DMAP is added, wherein the mass ratio of the added amount of DMAP to the polystyrene-based macroporous resin prepared in step (1) is 2:100. The mixture is heated to 80° C., stirred for reaction for 12 h, cooled to room temperature, filtered, washed and dried to obtain an adsorbent.

[0074] The adsorbent in this embodiment is used to adsorb the plasma solution containing radioactive elements. The adsorbent is effective for Sr 2+ The adsorption rate of Co 2+ The adsorption rate of U 4+ The adsorption rate is 96.8%.

[0075] Comparative Example

[0076] The adsorbent provided in this comparative example is the polystyrene-based macroporous resin containing chloromethyl groups obtained in step (1) of Example 1, which is not grafted with chitosan-coated MnO2 nanoparticles.

[0077] The adsorbent in this comparative example was used to adsorb the plasma solution containing radioactive elements. The adsorbent was effective for Sr 2+ The adsorption rate of Co 2+ The adsorption rate of U 4+ The adsorption rate is 0.5%. It can be seen from Example 1, Example 2 and the comparative example that the polystyrene-based macroporous resin of MnO2 nanoparticles without chitosan coating has basically no adsorption capacity for radioactive elements, while the adsorbents in Example 1 and Example 2 have good adsorption capacity for radioactive elements.

[0078] Although the disclosure is disclosed as above, the protection scope of the disclosure is not limited thereto. Those skilled in the art may make various changes and modifications without departing from the spirit and scope of the disclosure, and these changes and modifications will fall within the protection scope of the present invention.

Claims

1. An adsorbent, characterized in that: The adsorbent uses a polystyrene-based macroporous resin containing chloromethyl as a carrier and immobilizes an adsorption ligand. The adsorption ligand is a chitosan-coated MnO2 nanoparticle. The chitosan on the surface of the MnO2 nanoparticle reacts with the chloromethyl group and is immobilized on the carrier.

2. The adsorbent according to claim 1, characterized in that The chitosan-coated MnO2 nanoparticles are formed by the reaction of MnO2 nanoparticles with polyethylene oxide grafted on the surface and chitosan, wherein the polyethylene oxide is grafted on the surface of the MnO2 nanoparticles through covalent bonds.

3. The adsorbent according to claim 1, characterized in that In the adsorption ligand, the mass ratio of the MnO2 nanoparticles to the polystyrene-based macroporous resin containing chloromethyl groups is 0.01:1 to 0.3:1, and the mass ratio of the chitosan to the polystyrene-based macroporous resin containing chloromethyl groups is 0.2:1 to 0.4:

1.

4. A method for preparing an adsorbent, characterized in that: For preparing the adsorbent according to any one of claims 1 to 3, the preparation method comprises the following steps: Preparation of polystyrene-based macroporous resins containing chloromethyl groups; Chitosan was grafted onto the surface of MnO2 nanoparticles to prepare chitosan-coated MnO2 nanoparticles; Under alkaline conditions, the amino groups in the chitosan-coated MnO2 nanoparticles react with the chloromethyl groups in the polystyrene-based macroporous resin, and the chitosan-coated MnO2 nanoparticles are immobilized on the polystyrene-based macroporous resin to obtain the adsorbent.

5. The method for preparing an adsorbent according to claim 4, characterized in that: The method of grafting chitosan onto the surface of MnO2 nanoparticles to obtain chitosan-coated MnO2 nanoparticles comprises: The MnO2 nanoparticles, aminosilane coupling agent and grafting compound are reacted, and the grafting compound is grafted to the surface of the MnO2 nanoparticles through covalent bonds to obtain activated MnO2 nanoparticles, and the grafting compound is a compound containing polyethylene oxide; The activated MnO2 nanoparticles are reacted with chitosan, and the chitosan is grafted onto the polyethylene oxide on the surface of the activated MnO2 nanoparticles to obtain the chitosan-coated MnO2 nanoparticles.

6. The method for preparing an adsorbent according to claim 5, characterized in that: The step of reacting the activated MnO2 nanoparticles with chitosan, wherein the chitosan is grafted onto the polyethylene oxide on the surface of the activated MnO2 nanoparticles, comprises: Under acidic conditions, the activated MnO2 nanoparticles and the chitosan are added to a buffer solution, and ammonium cerium nitrate is used as an initiator. The reaction is stirred at 40° C. to 50° C. for 8 h to 12 h to graft the chitosan onto the polyethylene oxide on the surface of the activated MnO2 nanoparticles.

7. The method for preparing an adsorbent according to claim 5, characterized in that: The step of reacting the MnO2 nanoparticles, the aminosilane coupling agent and the grafting compound, wherein the grafting compound is grafted to the surface of the MnO2 nanoparticles through a covalent bond, comprises: The MnO2 nanoparticles are dispersed in a chloroform solution, an aminosilane coupling agent is added to the chloroform solution, and the solution is stirred and reacted at 45°C to 55°C for 8h to 12h, and then an excess of the grafted compound is added, and the temperature is raised to 50°C to 60°C and the solution is stirred and reacted for 8h to 12h, so that the grafted compound is grafted to the surface of the MnO2 nanoparticles through covalent bonds.

8. The method for preparing an adsorbent according to claim 4, characterized in that: The method comprises: reacting the amino groups in the chitosan-coated MnO2 nanoparticles with the chloromethyl groups in the polystyrene-based macroporous resin under alkaline conditions, comprising: Under alkaline conditions, the chitosan-coated MnO2 nanoparticles are mixed with the polystyrene-based macroporous resin, and DMAP is used as a catalyst. The reaction is stirred at 70° C. to 80° C. for 8 h to 12 h, so that the chitosan-coated MnO2 nanoparticles are immobilized on the polystyrene-based macroporous resin.

9. The method for preparing an adsorbent according to claim 4, characterized in that: The method for preparing a polystyrene-based macroporous resin containing chloromethyl comprises: Styrene and divinylbenzene are subjected to suspension polymerization to obtain polystyrene-based macroporous resin; The polystyrene-based macroporous resin and chloromethyl ether undergo a chloromethylation reaction under the action of a catalyst to prepare the polystyrene-based macroporous resin containing chloromethyl.

10. A blood perfusion device, characterized in that: The invention comprises the adsorbent as claimed in any one of claims 1 to 3, or comprises the adsorbent prepared by the preparation method as claimed in any one of claims 4 to 9.

Images