Adsorption resin for blood perfusion and preparation method thereof

By using adsorption resins prepared by components such as polystyrene, diethylenebenzene, dimethylaminoethyl methacrylate, acrylamide and chitosan in the blood perfusion technology, the problem of poor adsorption of organophosphorus pesticides in the prior art is solved, and efficient adsorption of organophosphorus toxins and protecting beneficial components in the blood is achieved.

CN119701889APending Publication Date: 2025-03-28SISHUI XIERKANG PHARMACELICAL CO LTD
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Patent Information

Application Number
CN202411836089.5
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-12-13
Publication Date
2025-03-28

AI Technical Summary

Technical Problem

In the existing blood perfusion technology, commonly used activated carbon adsorbents have poor adsorption selectivity for organophosphorus pesticides, and while adsorbing organophosphorus pesticides, they will also absorb beneficial components in the blood, weakening their adsorption capacity.

Method used

An adsorption resin for blood perfusion is used, and its components include polystyrene, diethylene benzene, dimethylaminoethyl methacrylate, acrylamide and chitosan. Through the reasonable combination and copolymerization of these components, an adsorption resin with high efficiency adsorption of organophosphorus toxins and reducing adsorption of beneficial components in the blood is formed.

Benefits of technology

It has achieved efficient adsorption of organophosphorus toxins, while minimizing the adsorption of beneficial components such as coagulation factors and white blood cells in the blood, and protecting the normal physiological functions of the blood.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention relates to the field of blood purification, and particularly discloses adsorption resin for blood perfusion and a preparation method of the adsorption resin. The adsorption resin for blood perfusion is prepared from polystyrene, divinylbenzene, dimethylaminoethyl methacrylate, acrylamide, chitosan and a pore-foaming agent. The preparation method comprises the following steps: uniformly stirring polystyrene, divinylbenzene, dimethylaminoethyl methacrylate and acrylamide at normal temperature to form a mixture; adding an initiator and a pore-foaming agent into the mixture, and stirring, wherein the use amount of the initiator is 0.5-1.5% of the total mass of the mixture; heating the mixture to 60-80 DEG C in a nitrogen environment, and reacting for 12-16 hours to obtain adsorption resin; placing adsorption resin in the chitosan solution, heating to 50 DEG C, and reacting for 3 hours; and after the reaction is finished, washing and drying a product to obtain the adsorbent resin for blood perfusion. The adsorbent resin for blood perfusion has the advantages that organic phosphorus is efficiently adsorbed, and blood cell adsorption damage is reduced.
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Description

Technical Field

[0001] The present application relates to the field of blood purification, and more specifically, to an adsorption resin for blood perfusion and a preparation method thereof. Background Art

[0002] Hemoperfusion is a blood purification technology that removes toxins and harmful substances from the blood by introducing the patient's blood into an adsorbent material. Its technical principle is mainly based on physical adsorption and chemical adsorption, relying on the high surface area and active sites of the adsorbent material to adsorb the target toxins in the blood.

[0003] Blood perfusion is introduced into the perfusion device (also called adsorption column) through a pipeline and flows through the adsorption material. When the blood flows through the adsorption material, the toxins or harmful substances in it are captured by the adsorbent and fixed on the surface or internal pores of the adsorption material. The adsorbed blood then flows back to the patient's body through the circuit to achieve the purpose of removing toxins. Acute organophosphorus pesticide poisoning (AOPP) refers to a series of injuries mainly caused by damage to the nervous system after organophosphorus pesticides enter the human body in a short period of time. Clinically, it mainly includes cholinergic excitement or crisis in acute poisoning patients, followed by intermediate syndrome (IMS) and delayed peripheral neuropathy (OPIDPN). Millions of people suffer from AOPP every year worldwide, of which about 300,000 people die, and most of them occur in developing countries.

[0004] The activated carbon adsorbent commonly used in hemoperfusion has relatively poor adsorption selectivity for organophosphorus pesticides. While adsorbing organophosphorus pesticides, it also adsorbs some beneficial components in the blood, such as coagulation factors and white blood cells, further weakening the adsorption capacity of activated carbon. Therefore, a new adsorption material is needed that can efficiently adsorb organophosphorus toxins and reduce the adsorption of beneficial components in the blood. Summary of the invention

[0005] In order to solve the above problems, the present application provides an adsorption resin for blood perfusion and a preparation method thereof.

[0006] The present application provides an adsorption resin for blood perfusion using the following technical solution: An adsorption resin for blood perfusion comprises, by weight, 34-38 parts of polystyrene, 2-6 parts of divinylbenzene, 5-10 parts of dimethylaminoethyl methacrylate, 5-10 parts of acrylamide, 1-5 parts of chitosan and 20-30 parts of a porogen.

[0007] By adopting the above technical scheme, the copolymer synthesized from polystyrene and divinylbenzene as the main skeleton structure of the resin has good chemical stability and mechanical strength. Its cross-linked structure can provide abundant adsorption sites, creating conditions for the attachment of organophosphorus pesticide molecules. The dimethylamino group in the dimethylaminoethyl methacrylate molecule has strong alkalinity and can form chemical bonds with the phosphorus atoms in the organophosphorus molecules. This interaction enhances the adsorption selectivity of the resin for organophosphorus toxins, allowing the resin to capture organophosphorus molecules more accurately and improve the adsorption efficiency of organophosphorus. After acrylamide participates in the copolymerization reaction, the hydrophilicity of the resin is increased, which helps the adsorption resin to better contact the organophosphorus toxins in the blood environment. The addition of chitosan significantly improves the biocompatibility of the resin. Chitosan can reduce the adverse effects on beneficial components such as blood cells and coagulation factors in the blood environment. It can form a barrier on the surface of the resin, making it difficult for beneficial components in the blood to be adsorbed, while not affecting the adsorption function of the resin for organophosphorus toxins. Through the reasonable combination and copolymerization of the above components, the adsorption resin formed has a unique chemical structure and surface properties. This structure enables the resin to achieve efficient adsorption of organophosphorus toxins when faced with multiple components in the blood, relying on the different interaction mechanisms between each component and the organophosphorus toxins and beneficial components, while minimizing the adsorption of beneficial components such as coagulation factors and white blood cells in the blood, effectively protecting the normal physiological functions of the blood.

[0008] Optionally, 20-30 parts of amine-modified activated carbon are also included.

[0009] Optionally, the preparation method of the amine-modified activated carbon is: The activated carbon and toluene are mixed in a mass ratio of 1:(8-12) and dispersed by ultrasound to form a suspension; 3-aminopropyltriethoxysilane is added dropwise to the above suspension in a ratio of activated carbon to 3-aminopropyltriethoxysilane of (5-10):1, and dibutyltin dilaurate is added at the same time, the amount of dibutyltin dilaurate is 1-2% of the mass of 3-aminopropyltriethoxysilane, and the mixture is refluxed at 80-100° C. for 12-24 hours under nitrogen protection; After the reaction is completed, the reaction mixture is cooled, separated, washed and dried to obtain amine-modified activated carbon.

[0010] By adopting the above technical scheme, during the preparation of amine-modified activated carbon, amine groups were introduced on the surface of activated carbon by 3-aminopropyltriethoxysilane. Amine groups have strong alkalinity and lone pairs of electrons, and can form hydrogen bonds and electrostatic interactions with phosphorus atoms in organophosphorus molecules. This specific interaction makes amine-modified activated carbon have a strong affinity for organophosphorus toxins, and can capture organophosphorus molecules more accurately, thereby significantly enhancing the adsorption capacity of the entire adsorption resin system for organophosphorus toxins.

[0011] Optionally, the pore size distribution of the activated carbon is 20-80 nm.

[0012] By adopting the above technical solution, the pore size of activated carbon with a pore size distribution of 20-80nm can be well adapted to the size of various organophosphorus molecules, which can not only accommodate smaller organophosphorus molecules, but also provide sufficient space for larger molecules of organophosphorus to enter the pores for adsorption. The diameter of blood cells is usually between a few microns and more than ten microns, which is much larger than the pore size of 20-80nm. This huge size difference prevents blood cells from entering the pores of activated carbon, thus forming a physical barrier, which effectively prevents blood cells from being adsorbed in the pores of activated carbon and being damaged.

[0013] Optionally, the deacetylation degree of the chitosan is 85-95%.

[0014] By adopting the above technical solution, chitosan with a deacetylation degree of 85-95% also has a good protective effect on coagulation factors. The interaction between the amino groups in the chitosan molecules and the coagulation factor molecules can stabilize the structure and function of the coagulation factors to a certain extent, avoiding blockage caused by coagulation during blood perfusion.

[0015] Optionally, the porogen is poly(N-isopropylacrylamide).

[0016] By adopting the above technical solution and utilizing the temperature responsiveness of poly(N-isopropylacrylamide), the adsorption performance of the adsorption resin can be intelligently regulated. By controlling the temperature, the size and openness of the pores can be adjusted, thereby affecting the diffusion rate and adsorption affinity of the organic phosphorus.

[0017] In a second aspect, the present application provides a method for preparing an adsorption resin for blood perfusion, using the following technical solution: A method for preparing an adsorption resin for blood perfusion comprises the following steps: Stirring polystyrene, divinylbenzene, dimethylaminoethyl methacrylate, and acrylamide to form a mixture; Adding an initiator and a porogen to the above mixture and stirring, wherein the amount of the initiator is 0.5-1.5% of the total mass of the mixture; The mixture is heated to 60-80° C. in a nitrogen environment and reacted for 12-16 hours to obtain an adsorption resin; The adsorption resin was placed in the chitosan solution, heated to 50°C, and reacted for 3 hours; After the reaction is completed, the product is washed and dried to obtain an adsorption resin for blood perfusion.

[0018] By adopting the above technical solution, the polymerization reaction forms a resin structure with a stable skeleton of polystyrene-divinylbenzene copolymer and abundant adsorption sites. The porogen gives the resin a suitable pore structure to increase the specific surface area to improve the adsorption efficiency; at the same time, nitrogen protection and strict control of reaction temperature and time ensure the polymerization quality, avoid oxygen interference and incomplete polymerization or excessive cross-linking and other problems that affect the resin performance. The addition of chitosan improves the biocompatibility of the adsorption resin and reduces the adverse effects on the beneficial components of the blood. Unreacted monomers, initiators and other impurities can be effectively removed by washing to ensure the purity of the product and avoid adverse effects on adsorption performance and safety; vacuum drying can make the resin reach a suitable dry state to ensure its storage and subsequent use in blood perfusion equipment. Stable quality and performance.

[0019] Optionally, include the following steps: Stirring polystyrene, divinylbenzene, dimethylaminoethyl methacrylate, acrylamide and amine-modified activated carbon to form a mixture; Adding an initiator and a porogen to the above mixture and stirring and mixing, wherein the amount of the initiator is 0.5-1.5% of the total mass of the mixture; heating the mixture to 60-80° C. in a nitrogen environment and reacting for 12-16 hours to obtain an adsorption resin; The adsorption resin was placed in the chitosan solution, heated to 50°C, and reacted for 3 hours; After the reaction is completed, the product is washed and dried to obtain an adsorption resin for blood perfusion.

[0020] Optionally, a zwitterionic polymer layer is further added to the surface of the adsorption resin for blood perfusion.

[0021] Optionally, the method for preparing the zwitterionic polymer layer on the surface of the adsorption resin for blood perfusion is: Dimethylaminoethyl methacrylate is prepared into a solution with a concentration of 1-2 mol / L; Under nitrogen protection, the solution is heated to 60-70°C and azobisisobutyronitrile is added, wherein the amount of azobisisobutyronitrile is 0.5-1% of the molar amount of dimethylaminoethyl methacrylate; Adding 1,3-propane sultone to the solution, wherein the molar ratio of 1,3-propane sultone to dimethylaminoethyl methacrylate is 1:(1-1.2), reacting for 4-6 hours, and obtaining a zwitterionic monomer having a quaternary ammonium salt cation and a sulfonate group; The blood perfusion adsorption resin and the zwitterionic monomer are mixed in a mass ratio of (6-8):1, and then 20-30% of N,N-dimethylformamide and 1-3% of azobisisobutyronitrile are added to the total mass of the mixture, and the mixture is reacted at 70-80°C for 8-12 hours. After the reaction is completed, the mixture is cooled, washed, and dried to obtain the blood perfusion adsorption resin containing the zwitterionic polymer layer.

[0022] By adopting the above technical solution, the zwitterionic polymer layer contains quaternary ammonium salt cations and sulfonate groups at the same time. In the blood environment, this structure can effectively inhibit the adsorption of proteins in the blood through electrostatic action and hydration. Proteins carry charges, and the cations and anions of the zwitterionic polymer layer can interact with the charges on the protein molecules to form a dynamic balance, making it difficult for proteins to form stable adsorption on the resin surface. The presence of the zwitterionic polymer layer can also effectively resist the adhesion of blood cells. The surface of blood cells also carries charges, and the interaction mode with the zwitterionic polymer layer is similar to that of proteins. This interaction prevents blood cells from easily adhering to the resin surface when they come into contact with it, maintaining the normal flow state of blood cells. The zwitterionic polymer layer changes the charge distribution and microenvironment of the resin surface to a certain extent, making it easier for organophosphorus toxin molecules to interact with the adsorption sites on the resin surface, thereby further enhancing the adsorption capacity of organophosphorus toxins and improving the therapeutic effect of organophosphorus poisoning during blood perfusion.

[0023] In summary, this application has the following beneficial effects: 1. This application uses a copolymer of polystyrene and divinylbenzene as the main adsorption resin, combined with the chemical bonding effect of dimethylaminoethyl methacrylate on organic phosphorus, the hydrophilicity of acrylamide, and the biocompatibility and barrier effect of chitosan, to achieve efficient adsorption of organic phosphorus toxins, while minimizing the adsorption of beneficial components such as coagulation factors and white blood cells in the blood, thereby protecting the normal physiological function of the blood.

[0024] 2. In the present application, it is preferred to introduce amine groups on the surface of activated carbon, and the amine groups form hydrogen bonds and electrostatic interactions with phosphorus atoms in organic phosphorus molecules to enhance the adsorption capacity of organic phosphorus toxins. The pore size of activated carbon is distributed in 20-80nm, which is suitable for the size of organic phosphorus molecules, allowing them to enter and exit the pores for adsorption. At the same time, blood cells cannot enter because their size is much larger than the pore size, thus avoiding damage to blood cells. These designs significantly enhance the adsorption capacity of the adsorption resin system for organic phosphorus toxins and avoid harming blood cells.

[0025] 3. The method of the present application controls the reaction temperature and time to carry out the polymerization reaction under nitrogen protection, uses a porogen to form a suitable pore structure, uses a copolymer of polystyrene and divinylbenzene as a skeleton, combines dimethylaminoethyl methacrylate and acrylamide to enrich the adsorption sites, and then adds chitosan to improve biocompatibility. Finally, impurities are removed by alternating washing with deionized water and ethanol and vacuum drying to ensure a dry state, thereby improving the adsorption efficiency, ensuring the polymerization quality, reducing the adverse effects on beneficial components in the blood, and ensuring the purity of the product and the stability of the quality and performance during use. DETAILED DESCRIPTION

[0026] The present application is further described in detail below in conjunction with the examples. It is particularly noted that if no specific conditions are specified in the following examples, the experiments are carried out according to conventional conditions or the conditions recommended by the manufacturer. Unless otherwise specified, the raw materials used in the following examples can be obtained from common commercial sources.

[0027] Preparation example of amine-modified activated carbon Preparation Example 1 Preparation of an amine-modified activated carbon: Prepare activated carbon with a particle size of 0.3-0.1 mm and a pore size distribution of 20-80 nm.

[0028] Disperse 10 kg of activated carbon in 100 kg of anhydrous toluene solution, and form a suspension by ultrasonic dispersion for 15 minutes; then slowly drop 1.5 kg of 3-aminopropyltriethoxysilane into the above suspension, and simultaneously add dibutyltin dilaurate in an amount of 1.5% of the mass of 3-aminopropyltriethoxysilane, and heat to 90° C. under nitrogen protection for reflux reaction for 16 hours; After the reaction was completed, the reaction mixture was cooled to room temperature, the activated carbon was separated, and washed alternately with toluene and anhydrous ethanol, and the washed amine-modified activated carbon was vacuum dried at 60°C.

[0029] Preparation Example 2 Preparation of an amine-modified activated carbon: The difference from Preparation Example 1 is that 1 kg of 3-aminopropyltriethoxysilane is slowly added dropwise to the suspension.

[0030] Preparation Example 3 Preparation of an amine-modified activated carbon: The difference from Preparation Example 1 is that 2 kg of 3-aminopropyltriethoxysilane is slowly added dropwise to the suspension.

[0031] Preparation Example 4 Preparation of an amine-modified activated carbon: The difference from Preparation Example 1 is that no dibutyltin dilaurate is added.

[0032] Preparation Example 5 Preparation of an amine-modified activated carbon: The difference from Preparation Example 1 is that the pore size distribution of the activated carbon is 80-200nm. Example

[0033] Example 1 A method for preparing an adsorption resin for blood perfusion: 3.6 kg of polystyrene, 0.4 kg of divinylbenzene, 0.8 kg of dimethylaminoethyl methacrylate and 0.8 kg of acrylamide were added into a reactor, stirred at 80 r / min for 20 min by a stirrer, and then 0.05 kg of azobisisobutyronitrile initiator and 2.5 kg of poly(N-isopropylacrylamide) porogen were added into the reactor; Under nitrogen protection, the materials in the reactor were stirred evenly, heated to 70°C and then kept warm, reacted for 14 hours to obtain an adsorption resin; the adsorption resin was naturally cooled to room temperature in the reactor, the adsorption resin was taken out and transferred to a clean container, 0.3 kg of chitosan was added to the container containing the adsorption resin, the deacetylation degree of chitosan was 90%, and water was added to completely cover the surface of the adsorption resin, the container was stirred to completely dissolve the chitosan, and the temperature was raised to 50°C after stirring evenly, and reacted for 3 hours; After the reaction was completed, the adsorption resin was washed twice with deionized water and ethanol alternately, and after washing, it was transferred to a vacuum drying oven and vacuum dried at 40° C. for 6 h to obtain the adsorption resin for blood perfusion.

[0034] Example 2 A method for preparing an adsorption resin for blood perfusion: The difference from Example 1 is that the raw material dosage is 3.4 kg polystyrene, 0.6 kg divinylbenzene, 0.5 kg dimethylaminoethyl methacrylate, 0.5 kg acrylamide, 0.04 kg azobisisobutyronitrile, 2 kg poly(N-isopropylacrylamide) porogen, and 0.1 kg chitosan.

[0035] Example 3 A method for preparing an adsorption resin for blood perfusion: The difference from Example 1 is that the raw materials used are 3.8 kg polystyrene, 0.2 kg divinylbenzene, 1 kg dimethylaminoethyl methacrylate and 1 kg acrylamide, 0.06 kg azobisisobutyronitrile, 3 kg poly(N-isopropylacrylamide) porogen, and 0.5 kg chitosan.

[0036] Example 4 A method for preparing an adsorption resin for blood perfusion: 3.6 kg of polystyrene, 0.4 kg of divinylbenzene, 0.8 kg of dimethylaminoethyl methacrylate, 0.8 kg of acrylamide, and 2.5 kg of amine-modified activated carbon were added to a reactor, stirred at 80 r / min for 20 min by a stirrer, and then 0.05 kg of azobisisobutyronitrile and 2.5 kg of poly(N-isopropylacrylamide) porogen were added to the reactor; the amine-modified activated carbon was prepared by Preparation Example 1; Under nitrogen protection, the materials in the reactor were stirred evenly, heated to 70°C and then kept warm, reacted for 6 hours to obtain an adsorption resin; the adsorption resin was naturally cooled to room temperature in the reactor, the adsorption resin was taken out and transferred to a clean container, 0.3 kg of chitosan was added to the container containing the adsorption resin, the deacetylation degree of chitosan was 90%, and water was added to completely cover the surface of the adsorption resin, the container was stirred to completely dissolve the chitosan, and the temperature was raised to 50°C after stirring evenly, and reacted for 3 hours; After the reaction was completed, the adsorption resin was washed twice with deionized water and ethanol alternately, and after washing, it was transferred to a vacuum drying oven and vacuum dried at 40° C. for 6 h to obtain the adsorption resin for blood perfusion.

[0037] Example 5 A method for preparing an adsorption resin for blood perfusion: The difference from Example 4 is that the added amount of amine-modified activated carbon is 2 kg.

[0038] Example 6 A method for preparing an adsorption resin for blood perfusion: The difference from Example 4 is that the added amount of amine-modified activated carbon is 3 kg.

[0039] Example 7 A method for preparing an adsorption resin for blood perfusion: The difference from Example 4 is that the amine-modified activated carbon is prepared by Preparation Example 2.

[0040] Example 8 A method for preparing an adsorption resin for blood perfusion: The difference from Example 4 is that the amine-modified activated carbon is prepared by Preparation Example 3.

[0041] Example 9 A method for preparing an adsorption resin for blood perfusion, which is different from Example 4 in that: After the adsorption resin for blood perfusion is prepared, the following treatments are required: Dissolve dimethylaminoethyl methacrylate in N,N-dimethylformamide to prepare a solution with a concentration of 1.5 mol / L. Heat the solution to 65°C under nitrogen protection and add azobisisobutyronitrile in an amount of 0.8% of the molar amount of dimethylaminoethyl methacrylate. 1,3-propane sultone was added dropwise to the solution, the molar ratio of 1,3-propane sultone to dimethylaminoethyl methacrylate was 1:1.1, and the mixture was reacted for 5 hours after the addition was completed to obtain a zwitterionic monomer having a quaternary ammonium salt cation and a sulfonate group; 7 kg of blood perfusion adsorption resin and 1 kg of zwitterionic monomer were mixed in a clean container, and then 25% of N, N-dimethylformamide and 2% of azobisisobutyronitrile were added to the total mass of the mixture, and the mixture was reacted at 75°C for 10 hours. After the reaction, the product was cooled to room temperature, washed twice with deionized water and ethanol alternately, and then transferred to a vacuum drying oven and vacuum dried at 40°C for 6 hours to obtain a blood perfusion adsorption resin containing a zwitterionic polymer layer.

[0042] Example 10 A method for preparing an adsorption resin for blood perfusion, which is different from Example 9 in that 6 kg of the adsorption resin for blood perfusion and 1 kg of zwitterionic monomer are mixed in a clean container.

[0043] Embodiment 11 A method for preparing an adsorption resin for blood perfusion, which is different from Example 9 in that 8 kg of the adsorption resin for blood perfusion and 1 kg of zwitterionic monomer are mixed in a clean container.

[0044] Example 12 A method for preparing an adsorption resin for blood perfusion is different from that of Example 1 in that toluene is used as a porogen.

[0045] Embodiment 13 A method for preparing an adsorption resin for blood perfusion, which is different from Example 4 in that: the amine-modified activated carbon is prepared by Preparation Example 5.

[0046] Comparative Example Comparative Example 1 A method for preparing an adsorption resin for blood perfusion, which is different from Example 1 in that dimethylaminoethyl methacrylate is not added.

[0047] Comparative Example 2 A method for preparing an adsorption resin for blood perfusion, which is different from Example 1 in that the deacetylation degree of chitosan is 80%.

[0048] Comparative Example 3 A method for preparing an adsorption resin for blood perfusion, which is different from Example 4 in that: the amine-modified activated carbon is prepared by Preparation Example 4.

[0049] Performance testing Detection Methods 14 portions of 500 g fresh whole blood of pigs were extracted, and heparin was added to prevent coagulation. Dimethoate was selected as an organophosphorus pesticide. The organophosphorus pesticide was added to the pig blood to make its concentration reach 1.2 μg / mL. The pig blood was treated with a blood perfusion machine, and the adsorption materials in the blood perfusion machine were respectively the adsorption resins prepared in the embodiment / comparative example. After one perfusion, the organophosphorus concentration was detected, and the loss ratio of blood cells was detected.

[0050] Table 1 Experimental data Combining Example 1 and Comparative Examples 1-2 and Table 1, it can be seen that the concentration of organic phosphorus after treatment in Example 1 is 0.42 μg / mL, and the concentration of organic phosphorus after treatment in Comparative Example 1 is 0.79 μg / mL. This shows that dimethylaminoethyl methacrylate plays an important role in the adsorption of organic phosphorus. The dimethylamino group in its molecule can form a chemical bond with the phosphorus atom in the organic phosphorus molecule, which enhances the adsorption selectivity of the resin to organic phosphorus toxins and improves the adsorption efficiency of organic phosphorus. The blood cell loss rate in Example 1 is 4.8%, and the blood cell loss rate in Comparative Example 2 is 8.6%. It shows that chitosan with a deacetylation degree of 85-95% has a good protective effect on coagulation factors. The amino groups in the chitosan molecules interact with the coagulation factor molecules, which can stabilize the structure and function of the coagulation factors and avoid blockage caused by coagulation during blood perfusion.

[0051] Combining Example 4 and Comparative Example 3 and Table 1, it can be seen that the main difference between Example 4 and Comparative Example 3 is whether dibutyltin dilaurate is added. From the data in Table 1, the organic phosphorus concentration after treatment in Example 4 is 0.31 μg / mL, and the organic phosphorus concentration after treatment in Comparative Example 3 is 0.40 μg / mL. It shows that dibutyltin dilaurate effectively promotes the reaction of 3-aminopropyltriethoxysilane with activated carbon during the preparation of amine-modified activated carbon. If dibutyltin dilaurate is not used as a catalyst, under the same time and temperature conditions, the reaction of 3-aminopropyltriethoxysilane with the surface groups of activated carbon proceeds very slowly, resulting in poor effect of amine-modified activated carbon obtained under the same preparation conditions.

[0052] Combining Examples 1-3 and Example 12 with Table 1, it can be seen that the present application uses a copolymer synthesized from polystyrene and divinylbenzene as the main material of the adsorption resin. Its stability is combined with the chemical bonding effect of dimethylaminoethyl methacrylate on organic phosphorus, the hydrophilicity of acrylamide, and the biocompatibility and barrier effect of chitosan. This composite resin system can efficiently adsorb organic phosphorus toxins, while reducing the adsorption of beneficial components such as coagulation factors and white blood cells in the blood, and protecting the normal physiological function of the blood. Examples 1-3 are mainly different in the amount of raw materials used, and the difference between Example 12 and Example 1 is that the porogen is different. From the data of organic phosphorus concentration and blood cell loss rate in Table 1, it can be seen that the change in the amount of raw materials will have a certain impact on the effect of organic phosphorus adsorption by the adsorption resin and the loss of blood cells. At the same time, the selection of poly (N-isopropylacrylamide) as a porogen is more conducive to the performance of the adsorption resin than the selection of toluene, because different porogens may affect the pore size and other structures of the resin, thereby affecting the adsorption of organic phosphorus and the effect on blood cells.

[0053] Combining Examples 1, 13 and Examples 4-8 with Table 1, it can be seen that after adding amine-modified activated carbon, the concentration of organic phosphorus has a significant downward trend, such as the concentration of organic phosphorus in Example 4 is 0.31 μg / mL, which is lower than 0.42 μg / mL in Example 1. Different addition amounts and treatment methods will affect the adsorption effect of the adsorption resin on organic phosphorus to a certain extent. The interaction between the amine group of the amine-modified activated carbon and the organic phosphorus molecules can enhance the adsorption capacity, and factors such as its pore size distribution will also have an effect on the adsorption effect.

[0054] Combining Example 1 and Examples 9-11 and Table 1, it can be seen that Examples 9-11 are further processed on the basis of Example 1 to obtain an adsorption resin for blood perfusion containing a zwitterionic polymer layer. From the data in Table 1, the organic phosphorus concentration after treatment in Example 9 is 0.23 μg / mL, and the blood cell loss rate is 3.5%, which is significantly improved compared with the organic phosphorus concentration of 0.42 μg / mL and the blood cell loss rate of 4.8% in Example 1. This shows that the adsorption efficiency of the adsorption resin for organic phosphorus can be further improved by generating a zwitterionic polymer layer through subsequent treatment, while better protecting the beneficial components in the blood and reducing the loss of blood cells.

[0055] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. An adsorption resin for blood perfusion, characterized in that: The components thereof include 34-38 parts of polystyrene, 2-6 parts of divinylbenzene, 5-10 parts of dimethylaminoethyl methacrylate, 5-10 parts of acrylamide, 1-5 parts of chitosan and 20-30 parts of porogen by weight.

2. The adsorption resin for blood perfusion according to claim 1, characterized in that: It also includes 20-30 parts of amine-modified activated carbon.

3. The adsorption resin for blood perfusion according to claim 2, characterized in that: The preparation method of the amine-modified activated carbon is: The activated carbon and toluene are mixed in a mass ratio of 1:(8-12) and dispersed by ultrasound to form a suspension; 3-aminopropyltriethoxysilane is added dropwise to the above suspension in a ratio of (5-10) to 3-aminopropyltriethoxysilane by mass, and dibutyltin dilaurate is added at the same time, the amount of dibutyltin dilaurate is 1-2% of the mass of 3-aminopropyltriethoxysilane, and the mixture is refluxed at 80-100°C for 12-24h under nitrogen protection; After the reaction is completed, the reaction mixture is cooled, separated, washed and dried to obtain amine-modified activated carbon.

4. The adsorption resin for blood perfusion according to claim 3, characterized in that: The pore size distribution of the activated carbon is 20-80nm.

5. The adsorption resin for blood perfusion according to claim 1, characterized in that: The deacetylation degree of the chitosan is 85-95%.

6. The adsorption resin for blood perfusion according to claim 1, characterized in that: The porogen is poly(N-isopropylacrylamide).

7. A method for preparing an adsorption resin for blood perfusion according to any one of claims 1 to 6, characterized in that: The following steps are involved: Stirring polystyrene, divinylbenzene, dimethylaminoethyl methacrylate, and acrylamide to form a mixture; Add initiator and porogen to the above mixture and stir, the amount of initiator is 0.5-1.5% of the total mass of the mixture; The mixture is heated to 60-80° C. in a nitrogen environment and reacted for 12-16 hours to obtain an adsorption resin; The adsorption resin was placed in the chitosan solution, heated to 50°C, and reacted for 3 hours; After the reaction is completed, the product is washed and dried to obtain an adsorption resin for blood perfusion.

8. The method for preparing the adsorption resin for blood perfusion according to claim 7, characterized in that: The following steps are involved: Stirring polystyrene, divinylbenzene, dimethylaminoethyl methacrylate, acrylamide and amine-modified activated carbon to form a mixture; Add initiator and porogen to the above mixture and stir to mix, the amount of initiator is 0.5-1.5% of the total mass of the mixture; The mixture is heated to 60-80° C. in a nitrogen environment and reacted for 12-16 hours to obtain an adsorption resin; The adsorption resin was placed in the chitosan solution, heated to 50°C, and reacted for 3 hours; After the reaction is completed, the product is washed and dried to obtain an adsorption resin for blood perfusion.

9. The method for preparing the adsorption resin for blood perfusion according to claim 7, characterized in that: A zwitterionic polymer layer is also added to the surface of the blood perfusion adsorption resin, and the preparation method of the zwitterionic polymer layer is as follows: Dimethylaminoethyl methacrylate is prepared into a solution with a concentration of 1-2 mol / L; Under nitrogen protection, the solution is heated to 60-70°C and azobisisobutyronitrile is added, wherein the amount of azobisisobutyronitrile is 0.5-1% of the molar amount of dimethylaminoethyl methacrylate; Adding 1,3-propane sultone to the solution, wherein the molar ratio of 1,3-propane sultone to dimethylaminoethyl methacrylate is 1:(1-1.2), reacting for 4-6 hours, and obtaining a zwitterionic monomer having a quaternary ammonium salt cation and a sulfonate group; The blood perfusion adsorption resin and the zwitterionic monomer are mixed in a mass ratio of (6-8):1, and then 20-30% of N,N-dimethylformamide and 1-3% of azobisisobutyronitrile are added to the total mass of the mixture, and the mixture is reacted at 70-80°C for 8-12 hours. After the reaction is completed, the mixture is cooled, washed, and dried to obtain the blood perfusion adsorption resin containing the zwitterionic polymer layer.

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