Chitosan-based blood perfusion adsorbent as well as preparation method and application thereof

Abstract

The invention relates to the field of materials, and particularly discloses a chitosan-based blood perfusion adsorbent as well as a preparation method and application thereof. According to the blood perfusion adsorbent, modified chitosan microspheres serve as a carrier, after chicoric acid is grafted on the surfaces of the modified chitosan microspheres, manganese dioxide nano-enzyme is immobilized, and the composite adsorbent is formed. According to the blood perfusion adsorbent provided by the invention, the manganese dioxide nano-enzyme is immobilized on the surface, so that active oxygen can be efficiently removed, and meanwhile, various free radicals can be removed; the chitosan microsphere has high adsorption capacity, can synergistically and effectively adsorb inflammatory factors in blood with the chitosan microsphere after being immobilized on the surface of the chitosan microsphere, improves the blood purification effect, has blood compatibility and safety, and can be used for blood purification treatment of patients with inflammations.

Description

Technical Field

[0001] The present application relates to the field of medical devices, and more specifically, to a chitosan-based blood perfusion adsorbent and a preparation method and application thereof. Background Art

[0002] Hemoperfusion technology is an extracorporeal blood purification method that removes harmful substances from the blood by drawing the patient's blood out of the body, passing it through a perfusion device filled with specific adsorbents, and then returning the purified blood to the patient. This technology has shown great potential in the treatment of many diseases, especially inflammatory diseases, such as severe hepatitis, psoriasis, sepsis, etc.

[0003] However, existing hemoperfusion adsorbents have limitations in removing inflammatory factors from the blood. The blood of patients with inflammatory diseases often contains high concentrations of inflammatory factors, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), etc. These factors are key mediators of inflammatory responses. Existing adsorbents have limited efficiency in removing these inflammatory factors, resulting in poor treatment effects. At the same time, inflammatory patients often experience increased oxidative stress due to inflammatory responses, which leads to increased levels of free radicals and reactive oxygen species in the blood. These substances damage cell nuclear tissues, and existing adsorbents are often helpless against such substances.

[0004] In view of this, it is necessary to develop a blood perfusion adsorbent for inflammatory patients to improve the blood perfusion purification effect of inflammatory patients. Summary of the invention

[0005] In order to improve the clearance rate of inflammatory factors, free radicals and reactive oxygen species during blood perfusion, while reducing hemolysis and safety, the present application provides a chitosan-based blood perfusion adsorbent, a preparation method and application thereof.

[0006] This application adopts the following technical solutions: In a first aspect, the present application provides a chitosan-based blood perfusion adsorbent, which uses modified chitosan microspheres as carriers, grafts chicoric acid on the surface, and then immobilizes manganese dioxide nanozymes to form a composite adsorbent for removing inflammatory factors in the blood of inflammatory patients.

[0007] The above technical scheme optimizes the material selection, surface modification and modification of the adsorbent, uses chitosan microspheres as carriers, which have good biocompatibility and mechanical strength, and after surface modification, grafts chicoric acid, uses chicoric acid as a connecting arm, and immobilizes manganese dioxide nanozymes on its surface.

[0008] Manganese dioxide nanozyme has three types of antioxidant enzyme activities, including superoxide dismutase-like, catalase-like, and glutathione peroxidase-like activities, which can efficiently remove reactive oxygen species and multiple free radicals at the same time; and it has high adsorption capacity itself. After being immobilized on the surface of chitosan microspheres, it can synergistically and effectively adsorb inflammatory factors in the blood with chitosan microspheres to improve the effect of blood purification. At the same time, since the chicoric acid molecule contains 2 adjacent carboxyl groups and 4 phenolic hydroxyl groups, it can serve as an intermediate bridge to provide a stable chemical bond to connect the chitosan microsphere carrier and the manganese dioxide nanozyme ligand. And through the modification of chicoric acid, the hydrophilicity of the adsorbent surface is enhanced, which helps to improve blood compatibility and reduce the risk of blood coagulation and platelet activation.

[0009] Furthermore, in a preferred embodiment of the present application, the modified chitosan microspheres are obtained by epoxidation modification of monodisperse chitosan microspheres. Epoxidation modification of the surface of chitosan microspheres can increase the structural stability of the chitosan microspheres and improve the chemical reaction activity of the microsphere surface, which is conducive to further grafting chicoric acid.

[0010] Preferably, in the preferred embodiment of the present application, the particle size of the chitosan microspheres is 100-200 μm, and the coefficient of variation CV is <5%. This type of chitosan microspheres has strong monodispersity, is not easy to agglomerate during the subsequent chemical modification process, and can provide a more consistent adsorption surface area and void structure during the blood perfusion process, which helps to improve the efficiency of blood perfusion.

[0011] Furthermore, in a preferred embodiment of the present application, the modification method of the modified chitosan microspheres comprises: (1) dispersing chitosan microspheres in an alkaline solution and ultrasonicating for 20-30 minutes to obtain a chitosan microsphere dispersion; (2) Adding 2,3-epoxypropyltrimethylammonium chloride and ferrous sulfate to the chitosan microsphere dispersion, reacting at a temperature of 40-60° C. for 7-9 hours under stirring, and washing.

[0012] Preferably, the ultrasound time is 24-26 min; Preferably, the reaction temperature is 45-55° C. for 7.5-8.5 h.

[0013] Furthermore, in a preferred embodiment of the present application, the mass ratio of the chitosan microspheres to the 2,3-epoxypropyltrimethylammonium chloride is 20-30:1; preferably, the mass ratio of the two is 23-26:1.

[0014] In a second aspect, the present application provides a method for preparing the above-mentioned blood perfusion adsorbent, which comprises: (1) epoxidation-modifying chitosan microspheres to obtain modified chitosan microspheres; (2) adding the modified chitosan microspheres to an ethanol aqueous solution containing chicoric acid, ultrasonicating for 40-50 min, adding stannous chloride, and reacting at 70-80° C. for 3-4 h to obtain chicoric acidified chitosan microspheres; Stannous chloride is used as a catalyst to help accelerate the reaction rate. Preferably, the reaction temperature is 73-77°C and the reaction time is 3.5-4h.

[0015] 1. The chicory acidified chitosan microspheres are dispersed in an ethylene glycol solution containing manganese nitrate hexahydrate, an alkali solution is added, a pyrolysis reaction is performed, and the hemoperfusion adsorbent is obtained after centrifugation and washing.

[0016] Manganese nitrate hexahydrate (Mn(NO 3 ) 2 6H 2 O) will decompose and form MnO when heated under alkaline conditions 2 , MnO free in solution 2 In the process of gradual formation, the chitosan microspheres acidified by chicory are captured and immobilized on the chitosan microspheres to form the blood perfusion adsorbent of the present application.

[0017] Furthermore, in a preferred embodiment of the present application, the mass ratio of the modified chitosan microspheres to chicoric acid is 15-20:1; preferably, the mass ratio is 16-18:1.

[0018] Furthermore, in a preferred embodiment of the present application, the mass ratio of the modified chitosan microspheres to manganese nitrate hexahydrate is 6-8:1; preferably, the mass ratio is 6.5-7.5:1.

[0019] Furthermore, in a preferred embodiment of the present application, the reaction temperature of the above-mentioned antipyretic reaction is 50-80°C, and the reaction time is 3-6h; preferably, the reaction temperature is 60-70°C, and the reaction time is 4-5h.

[0020] In a third aspect, the present application provides a use of the above-mentioned blood perfusion adsorbent in the preparation of a blood perfusion device.

[0021] In summary, this application has the following beneficial effects: 1. The blood perfusion adsorbent provided in the present application uses chitosan microspheres as carriers, which have good biocompatibility and mechanical strength. After surface modification, the structural stability of the chitosan microspheres can be increased, and the chemical reaction activity on the surface of the microspheres can be improved, which is conducive to further grafting chicoric acid.

[0022] 2. The hemoperfusion adsorbent provided by the present application uses chicoric acid as a connecting arm. Since the chicoric acid molecule contains two adjacent carboxyl groups and four phenolic hydroxyl groups, it can serve as an intermediate bridge to provide a stable chemical bond to connect the chitosan microsphere carrier and the manganese dioxide nanozyme ligand. And through the modification of chicoric acid, the hydrophilicity of the adsorbent surface is enhanced, which helps to improve blood compatibility and reduce the risk of blood coagulation and platelet activation.

[0023] 3. The blood perfusion adsorbent provided by the present application uses manganese dioxide nanozyme as a ligand. Manganese dioxide nanozyme has three types of antioxidant enzyme activities, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX)-like activities, which can efficiently remove reactive oxygen and multiple free radicals at the same time; and it has high adsorption capacity itself. After being immobilized on the surface of chitosan microspheres, it can synergistically and effectively adsorb inflammatory factors in the blood with chitosan microspheres to improve the effect of blood purification. DETAILED DESCRIPTION

[0024] The embodiments of the present invention will be described in detail below in conjunction with examples. However, those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention. The specific conditions not specified in the examples are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0025] The specific embodiments of the present invention are described in detail below. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention. Example

[0026] Example 1 This embodiment provides a chitosan-based blood perfusion adsorbent, and the preparation method thereof comprises the following steps: 1. Disperse 50 g of chitosan microspheres with a particle size of 100-200 μm (coefficient of variation CV<5%, purchased from Shanghai Pengzan Biotechnology Co., Ltd.) in 250 ml of 0.05 mol / L NaOH solution, and obtain chitosan microsphere dispersion after ultrasonic treatment for 25 min; 2. Add 2,3-epoxypropyltrimethylammonium chloride (2 g) to the chitosan microsphere dispersion, stir evenly, add a catalytic amount of ferrous sulfate, stir and react in a water bath at 50° C. for 8 h, then wash with ethanol and deionized water to obtain modified chitosan microspheres; 3. Dissolve chicoric acid (2 g) in 100 mL of 70% ethanol solution to obtain a chicoric acid solution; add 35 g of the modified chitosan microspheres obtained in step (2) into the chicoric acid solution, ultrasonicate for 45 min, add a catalytic amount of stannous chloride, heat the mixed reaction solution in a water bath at 72° C. for 4 h, filter, and wash with ethanol and deionized water in turn to obtain chicoric acidified chitosan microspheres; 4. Dissolve 5.3 g of manganese nitrate hexahydrate crystals in 200 mL of ethylene glycol to obtain a manganese nitrate hexahydrate solution, then add the chicory-acidified chitosan microspheres obtained in step (3), ultrasonically disperse for 30 min, place in a 60° C. water bath, add 4 mL of ammonia water while stirring at 250 rpm, continue the reaction for 5 h, centrifuge, wash with ethanol, wash with deionized water until neutral, and freeze-dry in a vacuum.

[0027] Example 2 This embodiment provides a chitosan-based blood perfusion adsorbent, and its preparation method is different from that of embodiment 1 in that step (2): 2,3-Epoxypropyltrimethylammonium chloride (2.5 g) was added to the chitosan microsphere dispersion, and after stirring evenly, a catalytic amount of ferrous sulfate was added. The mixture was stirred in a water bath at 50° C. for 8 h, and then washed with ethanol and deionized water to obtain modified chitosan microspheres.

[0028] Example 3 This embodiment provides a chitosan-based blood perfusion adsorbent, and its preparation method is different from that of embodiment 1 in that step (2): 2,3-Epoxypropyltrimethylammonium chloride (1.6 g) was added to the chitosan microsphere dispersion, and after stirring evenly, a catalytic amount of ferrous sulfate was added. The mixture was stirred in a water bath at 50° C. for 8 h, and then washed with ethanol and deionized water to obtain modified chitosan microspheres.

[0029] Example 4 This embodiment provides a chitosan-based blood perfusion adsorbent, and its preparation method is different from that of embodiment 1 in that step (2): 2,3-Epoxypropyltrimethylammonium chloride (2 g) was added to the chitosan microsphere dispersion, and after stirring evenly, a catalytic amount of ferrous sulfate was added, and the mixture was stirred in a water bath at 60° C. for 7 h, and then washed with ethanol and deionized water to obtain modified chitosan microspheres.

[0030] Example 5 This embodiment provides a chitosan-based blood perfusion adsorbent, and its preparation method is different from that of embodiment 1 in that step (2): 2,3-Epoxypropyltrimethylammonium chloride (2 g) was added to the chitosan microsphere dispersion, and after stirring evenly, a catalytic amount of ferrous sulfate was added, and the mixture was stirred in a water bath at 40° C. for 9 h, and then washed with ethanol and deionized water to obtain modified chitosan microspheres.

[0031] Example 6 This embodiment provides a chitosan-based blood perfusion adsorbent, and the preparation method thereof is different from that of embodiment 1 in that step (3): Dissolve chicoric acid (2 g) in 100 mL of 70% ethanol solution to obtain a chicoric acid solution; add 40 g of the modified chitosan microspheres obtained in step (2) into the chicoric acid solution, ultrasonicate for 45 min, add a catalytic amount of stannous chloride, heat the mixed reaction solution in a water bath at 72° C. for 4 h, filter, and wash with ethanol and deionized water in turn to obtain chicoric acidified chitosan microspheres.

[0032] Example 7 This embodiment provides a chitosan-based blood perfusion adsorbent, and the preparation method thereof is different from that of embodiment 1 in that step (3): Dissolve chicoric acid (2 g) in 100 mL of 70% ethanol solution to obtain a chicoric acid solution; add 30 g of the modified chitosan microspheres obtained in step (2) into the chicoric acid solution, ultrasonicate for 45 min, add a catalytic amount of stannous chloride, heat the mixed reaction solution in a water bath at 72° C. for 4 h, filter, and wash with ethanol and deionized water in turn to obtain chicoric acidified chitosan microspheres.

[0033] Example 8 This embodiment provides a chitosan-based blood perfusion adsorbent, and the preparation method thereof is different from that of embodiment 1 in that step (3): Dissolve chicoric acid (2 g) in 100 mL of 70% ethanol solution to obtain a chicoric acid solution; add 35 g of the modified chitosan microspheres obtained in step (2) into the chicoric acid solution, ultrasonicate for 45 min, add a catalytic amount of stannous chloride, heat the mixed reaction solution in a water bath at 80° C. for 3 h, filter, and wash with ethanol and deionized water in turn to obtain chicoric acidified chitosan microspheres.

[0034] Example 9 This embodiment provides a chitosan-based blood perfusion adsorbent, and the preparation method thereof is different from that of embodiment 1 in that step (3): Dissolve chicoric acid (2 g) in 100 mL of 70% ethanol solution to obtain a chicoric acid solution; add 35 g of the modified chitosan microspheres obtained in step (2) into the chicoric acid solution, ultrasonicate for 45 min, add a catalytic amount of stannous chloride, heat the mixed reaction solution in a water bath at 70° C. for 4 h, filter, and wash with ethanol and deionized water in turn to obtain chicoric acid-modified chitosan microspheres.

[0035] Example 10 This embodiment provides a chitosan-based blood perfusion adsorbent, and its preparation method is different from that of embodiment 1 in that step (4): 4.3 g of manganese nitrate hexahydrate crystals were dissolved in 200 mL of ethylene glycol to obtain a manganese nitrate hexahydrate solution, and then the chicory-acidified chitosan microspheres obtained in step (3) were added, ultrasonically dispersed for 30 min, placed in a 60° C. water bath, and 4 mL of ammonia water was added under stirring at 250 rpm. The reaction was continued for 5 h, centrifuged, washed with ethanol, washed with deionized water until neutral, and freeze-vacuum dried.

[0036] Embodiment 11 This embodiment provides a chitosan-based blood perfusion adsorbent, and its preparation method is different from that of embodiment 1 in that step (4): 5.8 g of manganese nitrate hexahydrate crystals were dissolved in 200 mL of ethylene glycol to obtain a manganese nitrate hexahydrate solution, and then the chicory-acidified chitosan microspheres obtained in step (3) were added, ultrasonically dispersed for 30 min, placed in a 60° C. water bath, and 4 mL of ammonia water was added under stirring at 250 rpm. The reaction was continued for 5 h, centrifuged, washed with ethanol, washed with deionized water until neutral, and freeze-vacuum dried.

[0037] Example 12 This embodiment provides a chitosan-based blood perfusion adsorbent, and its preparation method is different from that of embodiment 1 in that step (4): 5.3 g of manganese nitrate hexahydrate crystals were dissolved in 200 mL of ethylene glycol to obtain a manganese nitrate hexahydrate solution, and then the chicory-acidified chitosan microspheres obtained in step (3) were added, and ultrasonic dispersion was performed for 30 min. The solution was placed in a 50° C. water bath, and 4 mL of ammonia water was added under stirring at a speed of 250 rpm. The reaction was continued for 6 h. After centrifugation, the solution was washed with ethanol, washed with deionized water until neutral, and freeze-vacuum dried.

[0038] Example 13 This embodiment provides a chitosan-based blood perfusion adsorbent, and its preparation method is different from that of embodiment 1 in that step (4): 5.3 g of manganese nitrate hexahydrate crystals were dissolved in 200 mL of ethylene glycol to obtain a manganese nitrate hexahydrate solution, and then the chicory-acidified chitosan microspheres obtained in step (3) were added, and ultrasonic dispersion was performed for 30 min. The solution was placed in a water bath at 80° C., and 4 mL of ammonia water was added under stirring at 250 rpm. The reaction was continued for 3 h. After centrifugation, the solution was washed with ethanol, washed with deionized water until neutral, and freeze-vacuum dried.

[0039] Comparative Example Comparative Example 1 This comparative example provides a chitosan-based adsorbent, and its preparation method comprises: (1) Dissolve chicoric acid (2 g) in 100 mL of 70% ethanol solution to obtain a chicoric acid solution; add 35 g of chitosan microspheres (coefficient of variation CV <5%, purchased from Shanghai Pengzan Biotechnology Co., Ltd.) into the chicoric acid solution, sonicate for 45 min, add a catalytic amount of stannous chloride, heat the mixed reaction solution in a water bath at 72° C. for 4 h, filter, and wash with ethanol and deionized water in turn to obtain chicoric acidified chitosan microspheres; (2) 5.3 g of manganese nitrate hexahydrate crystals were dissolved in 200 mL of ethylene glycol to obtain a manganese nitrate hexahydrate solution, and then the chitosan microspheres acidified with chicory were added and ultrasonically dispersed for 30 min. 4 mL of ammonia water was added under stirring, and the solution was placed in a 60° C. water bath for reaction for 5 h. After centrifugation, the solution was washed with ethanol, washed with deionized water until neutral, and freeze-dried in a vacuum.

[0040] Comparative Example 2 This comparative example provides a chitosan-based adsorbent, and its preparation method comprises: 1. Disperse 50 g of chitosan microspheres with a particle size of 100-200 μm (coefficient of variation CV<5%, purchased from Shanghai Pengzan Biotechnology Co., Ltd.) in 250 ml of 0.05 mol / L NaOH solution, and obtain chitosan microsphere dispersion after ultrasonic treatment for 25 min; 2. Add 2,3-epoxypropyltrimethylammonium chloride (2 g) to the chitosan microsphere dispersion, stir evenly, add a catalytic amount of ferrous sulfate, stir and react in a water bath at 50° C. for 8 h, then wash with ethanol and deionized water to obtain modified chitosan microspheres; 3. Dissolve 5.3 g of manganese nitrate hexahydrate crystals in 200 mL of ethylene glycol to obtain a manganese nitrate hexahydrate solution, then add the modified chitosan microspheres obtained in step (2), ultrasonically disperse for 30 min, add 4 mL of ammonia water while stirring, place in a 60° C. water bath to react for 5 h, centrifuge, wash with ethanol, wash with deionized water until neutral, and freeze-dry in a vacuum.

[0041] Comparative Example 3 This comparative example provides a chitosan-based adsorbent, and its preparation method comprises: 1. Disperse 50 g of chitosan microspheres with a particle size of 100-200 μm (coefficient of variation CV<5%, purchased from Shanghai Pengzan Biotechnology Co., Ltd.) in 250 ml of 0.05 mol / L NaOH solution, and obtain chitosan microsphere dispersion after ultrasonic treatment for 25 min; 2. Add 2,3-epoxypropyltrimethylammonium chloride (2 g) to the chitosan microsphere dispersion, stir evenly, add a catalytic amount of ferrous sulfate, stir and react in a water bath at 50° C. for 8 h, then wash with ethanol and deionized water to obtain modified chitosan microspheres; 3. Dissolve chicoric acid (2 g) in 100 mL of 70% ethanol solution to obtain a chicoric acid solution; add 35 g of the modified chitosan microspheres obtained in step (2) into the chicoric acid solution, ultrasonicate for 45 min, add a catalytic amount of stannous chloride, heat the mixed reaction solution in a water bath at 72° C. for 4 h, filter, and wash with ethanol and deionized water in turn to obtain chicoric acidified chitosan microspheres.

[0042] Performance testing Detection method / test method 1. Blood compatibility test: According to GB / T16886.4-2003 Biological Evaluation of Medical Devices Part 4 Selection of Tests for Interaction with Blood, hemolysis experiments were performed on the adsorbents provided in Examples 1-13 and Comparative Examples 1-3.

[0043] The hemolysis rate was calculated according to the following formula: Hemolysis rate = (AB) / (CB)*100%, where A is the absorbance of the sample group; B is the absorbance of the negative control group; and C is the absorbance of the positive control group.

[0044] The experimental results show that the hemolysis rates of the adsorbents provided in Examples 1-13 and Comparative Examples 1-3 are all less than 3%, which meets the national standard (required to be less than 5%). This shows that the adsorbent provided in this application has good biocompatibility.

[0045] 2. Experiment on the clearance rate of inflammatory factors: The adsorption materials provided in Examples 1 and 6, and Comparative Examples 1-3 were wet packed into a column (φ1×10 cm), pre-washed with physiological saline, and then 30 mL of bovine plasma to which TNF-α and IL-6 had been added (wherein the concentration of TNF-α was 1 ng / mL and the concentration of IL-6 was 0.5 ng / mL) was added. The dynamic adsorption cycle was continued for 3 h. The contents of inflammatory factors TNF-α and IL-6 in bovine plasma before and after adsorption were tested, and the clearance rate was calculated. The results are shown in Table 1.

[0046] Table 1. As can be seen from Table 1, the adsorbents provided in Examples 1-13 of the present application can achieve a clearance rate of more than 80% for both inflammatory factors TNF-α and IL-6. In contrast, the clearance rates of Comparative Examples 1 and 2 for TNF-α and IL-6 are relatively weak, mainly because the chitosan microspheres are not modified and activated (Comparative Example 1) or because the chitosan microspheres are not grafted with chicoric acid (Comparative Example 2), resulting in only a small amount of manganese dioxide nanozymes being immobilized on the surface of the chitosan microspheres by electrostatic adsorption, thereby affecting their adsorption efficiency. In Comparative Example 3, since there is no manganese dioxide nanozyme immobilized on the surface of the adsorbent, it can only rely on the adsorption capacity of the chitosan microspheres themselves, so the clearance rates for both TNF-α and IL-6 are even weaker.

[0047] 3. Free radical scavenging rate experiment: A hydroxyl radical determination kit (purchased from Nanjing Jiancheng Biological Institute) was used to determine the scavenging ability of the adsorbents prepared in Example 1 and Comparative Examples 1-3. The determination was carried out according to the steps in the instructions of the kit, and the absorbance of the reaction solution at 550nm was measured with an ELISA instrument to calculate the scavenging rate of each adsorbent for hydroxyl radicals. The results are shown in Table 2: Table 2. As can be seen from Table 2, the adsorbent provided in Example 1 of the present application, due to the manganese dioxide nanozyme being immobilized on the surface of the chitosan microspheres through chicoric acid with a very stable bonding, exhibits a very strong scavenging rate for hydroxyl radicals. In Comparative Examples 1-2, due to the small amount of immobilized manganese dioxide nanozyme, only limited scavenging effect on hydroxyl radicals was exhibited. In Comparative Example 3, due to the absence of immobilized manganese dioxide nanozyme, the scavenging effect on hydroxyl radicals was very weak.

[0048] 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. A chitosan-based blood perfusion adsorbent, characterized in that: The blood perfusion adsorbent uses modified chitosan microspheres as carriers, grafts chicoric acid on the surface, and then immobilizes manganese dioxide nanozymes to form a composite adsorbent for removing inflammatory factors in the blood of inflammatory patients.

2. The chitosan-based blood perfusion adsorbent according to claim 1, characterized in that: The modified chitosan microspheres are obtained by epoxidation-modifying monodisperse chitosan microspheres.

3. The chitosan-based blood perfusion adsorbent according to claim 1, characterized in that: The particle size of the chitosan microspheres is 100-200 μm, and the coefficient of variation CV is less than 5%.

4. The chitosan-based blood perfusion adsorbent according to claim 1, characterized in that: The modification method of the modified chitosan microspheres comprises: Dispersing chitosan microspheres in alkaline solution, and ultrasonicating for 20-30 minutes to obtain chitosan microsphere dispersion; 2,3-Epoxypropyltrimethylammonium chloride and ferrous sulfate are added to the chitosan microsphere dispersion, and the mixture is reacted at 40-60° C. for 7-9 hours under stirring, and then washed.

5. The chitosan-based blood perfusion adsorbent according to claim 4, characterized in that: The mass ratio of the chitosan microspheres to the 2,3-epoxypropyltrimethylammonium chloride is 20-30:

1.

6. A method for preparing the blood perfusion adsorbent according to any one of claims 1 to 5, characterized in that: It includes: The chitosan microspheres are subjected to epoxidation modification to obtain modified chitosan microspheres; The modified chitosan microspheres are added to an ethanol aqueous solution containing chicoric acid, and after ultrasonication for 40-50 minutes, stannous chloride is added, and the mixture is reacted at 70-80° C. for 3-4 hours to obtain chicoric acidified chitosan microspheres; The chicory acidified chitosan microspheres are dispersed in an ethylene glycol solution containing manganese nitrate hexahydrate, an alkali solution is added, a pyrolysis reaction is carried out, and the hemoperfusion adsorbent is obtained after centrifugation and washing.

7. The method for preparing the hemoperfusion adsorbent according to claim 6, characterized in that: The mass ratio of the modified chitosan microspheres to chicoric acid is 15-20:

1.

8. The method for preparing the hemoperfusion adsorbent according to claim 6, characterized in that: The mass ratio of the modified chitosan microspheres to manganese nitrate hexahydrate is 6-8:

1.

9. The method for preparing the hemoperfusion adsorbent according to claim 6, characterized in that: The reaction temperature of the antipyretic reaction is 50-80° C., and the reaction time is 3-6 hours.

10. Use of the blood perfusion adsorbent according to any one of claims 1 to 5 in preparing a blood perfusion device.

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