Blood purification microsphere adsorbent and preparation method thereof

Abstract

The invention relates to a blood purification microsphere adsorbent and a preparation method thereof.The blood purification microsphere adsorbent comprises a core part and a shell layer wrapping the outer side of the core part; the core part is provided with a radial pore channel with the average pore diameter of 2-10 [mu] m; the shell layer is provided with a first spongy pore channel of which the average pore size is 0.1-0.5 mu m; the surface of the inner wall of the radial pore channel is coated with a protective layer, and second spongy pore channels with the average pore diameter of 0.5-2 microns are distributed on the protective layer; the protective layer is cellulose derived carbon; the average pore size of the first spongy pore channel is smaller than that of the second spongy pore channel; the radial pore channels are enclosed by lamellas, and the lamellas comprise halloysite nanotubes and cellulose derived carbon coated on the surfaces of the halloysite nanotubes. Compared with the prior art, the microsphere adsorbent has the beneficial effects that the adsorption efficiency and the maximum adsorption capacity of the microsphere adsorbent can be improved, and meanwhile, the adsorption safety is ensured.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to a blood purification microsphere adsorbent and its preparation method. Background Technology

[0002] With increasing environmental pollution and rising incidence of chronic diseases such as kidney failure and cancer, blood purification therapy is becoming increasingly important for maintaining patients' health. Blood purification microsphere adsorbents, as a novel treatment method, have shown great potential in removing harmful substances from the body. These adsorbents are typically designed into microsphere structures with specific pore size distributions, high specific surface areas, and good biocompatibility, enabling them to effectively remove toxins, inflammatory factors, and other metabolic waste products from the blood.

[0003] Although various blood purification adsorbents are currently available on the market, they still face some limitations and challenges in practical applications, such as low adsorption rates and capacities. Chinese patent CN117960123A discloses a composite microsphere adsorbent of halloysite nanotubes and cellulose-derived carbon, its preparation method, and its application. This adsorbent involves coating halloysite nanotubes into cellulose-derived carbon, resulting in a microsphere adsorbent with a sponge-like pore structure on the surface and a radial pore structure internally. While the aforementioned composite microsphere adsorbent improves adsorption efficiency, its application is limited to lipid adsorption, resulting in a relatively narrow scope and poor universality. Furthermore, when halloysite nanotubes come into direct contact with human blood, they may still trigger immune responses, platelet activation, or even hemolysis, increasing the treatment risks for patients. Given these issues, the overall performance of existing microsphere adsorbents needs improvement. Summary of the Invention

[0004] (a) Technical problems to be solved

[0005] In view of the above-mentioned shortcomings and deficiencies of the prior art, the present invention provides a blood purification microsphere adsorbent and its preparation method, which solves the technical problem that the working performance of existing blood purification microsphere adsorbents needs to be improved.

[0006] (II) Technical Solution

[0007] To achieve the above objectives, the main technical solutions adopted by the present invention include:

[0008] In a first aspect, embodiments of the present invention provide a blood purification microsphere adsorbent, the microsphere adsorbent comprising a core and a shell covering the outer side of the core;

[0009] The core has radial channels with an average pore size of 2-10 μm;

[0010] The shell has a first sponge-like channel with an average pore size of 0.1-0.5 μm;

[0011] The inner wall surface of the radial channels is covered with a protective layer, and the protective layer has a second sponge-like pore with an average pore size of 0.5-2 μm; the protective layer is cellulose-derived carbon.

[0012] The average pore diameter of the first sponge-like channel is smaller than the average pore diameter of the second sponge-like channel;

[0013] The radial channels are surrounded by sheets containing halloysite nanotubes and cellulose-derived carbon coated on their surfaces.

[0014] In a preferred embodiment of the present invention, the blood purification microsphere adsorbent has a shell layer of cellulose-derived carbon with a shell layer thickness of 10-150 μm.

[0015] In a preferred embodiment of the present invention, the blood purification microsphere adsorbent has a core diameter of 20-400 μm.

[0016] In a preferred embodiment of the present invention, the cellulose-derived carbon in the blood purification microsphere adsorbent is obtained by carbonizing cellulose;

[0017] The cellulose includes at least one of microcrystalline cellulose, nanocellulose, hydroxymethyl cellulose, cellulose ether, methylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, and carboxymethyl cellulose.

[0018] Secondly, embodiments of the present invention provide a method for preparing a blood purification microsphere adsorbent, comprising the following steps:

[0019] S1. Preparation of the core: According to the first specified ratio, the solubilizer, cellulose, dispersant and halloysite nanotubes are dispersed in the solvent to obtain the first precursor solution; the first precursor solution is dropped into liquid nitrogen, and after pre-freezing, freeze-drying and carbonization, a core with radial channels is formed; the inner diameter of the halloysite nanotubes is 10-30 nm.

[0020] S2. Surface treatment of radial channels in the core: According to the second specified ratio, the solubilizer, cellulose and dispersant are dispersed in the solvent to obtain the second precursor solution; the second precursor solution is adsorbed into the core by the impregnation method, and the core impregnated with the second precursor solution is pre-frozen and freeze-dried to form the second microspheres.

[0021] S3. Coating shell: According to the third specified ratio, the solubilizer, cellulose and dispersant are dispersed in the solvent to obtain the third precursor solution; the third precursor solution is coated on the surface of the second microspheres, and the second microspheres coated with the third precursor solution are pre-frozen, lyophilized and carbonized by gradient heating to form microsphere adsorbent.

[0022] The concentration of cellulose in the second precursor solution is lower than that in the first and third precursor solutions.

[0023] In a preferred embodiment of the present invention, in the preparation method of the blood purification microsphere adsorbent, in S1, the first specified ratio is the mass ratio of solubilizer, cellulose, dispersant and halloysite nanotubes and solvent as 3-5:6-10:0.1-0.5:1-3:12-15.

[0024] In a preferred embodiment of the present invention, in the preparation method of the blood purification microsphere adsorbent, in S2, the second specified ratio is a mass ratio of solubilizer, cellulose, dispersant and solvent of 3-5:3-5:0.1-0.5:16-20.

[0025] In S3, the third specified ratio is the mass ratio of solubilizer, cellulose, dispersant and solvent as 3-5:6-10:0.1-0.5:12-15;

[0026] The solubilizer is selected from one or more of N-methylmorpholine-N-oxide, 1-butyl-3-methylimidazolium chloride, and 1-ethyl-3-methylimidazolium acetate;

[0027] The dispersant is selected from one or more of polyethylene glycol, polysorbate, and polyethylene glycol octylphenyl ether;

[0028] The solvent is selected from one or more of water, ethanol, methanol, and dimethyl sulfoxide.

[0029] In a preferred embodiment of the present invention, in the preparation method of the blood purification microsphere adsorbent, in S1, the carbonization temperature is 300-1500 ℃ and the carbonization time is 5-10 h.

[0030] As a preferred embodiment of the present invention, in the preparation method of the blood purification microsphere adsorbent, S3, the gradient temperature carbonization includes two stages, and carbonization is carried out under an inert atmosphere: Stage 1: from room temperature to 200-300℃ at 1-2℃ / min, and hold for 1-2h; Stage 2: from room temperature to 700-800℃ at 3-4℃ / min, hold for 4-5h, and then cool down to room temperature.

[0031] In a preferred embodiment of the present invention, in the preparation method of the blood purification microsphere adsorbent, the pre-freezing time in S1-S3 is 1-5 min, and the pre-freezing time in S1 and S2 is greater than the pre-freezing time in S3.

[0032] In S1-S3, the freeze-drying temperature is -20 to -90 ℃, and the freeze-drying time is 12-120 h.

[0033] (III) Beneficial Effects

[0034] The beneficial effects of this invention are as follows: The blood purification microsphere adsorbent and its preparation method of this invention, due to the presence of radially shaped channels with larger pore sizes in the core and sponge-like channels with smaller minimum pore sizes in the shell, with the average pore size of the sponge-like channels in the protective layer falling between that of the core and shell channels, effectively increases the specific surface area. Blood enters the core from the shell, forming expanded channels, which facilitates sufficient mass transfer and adsorption, thus increasing the overall adsorption efficiency of the microsphere adsorbent. Simultaneously, the shell's small pore size prevents large protein molecules from entering and clogging the larger radially shaped channels. Furthermore, the protective layer completely encapsulates the halloysite nanotubes, avoiding the risks of hemolysis and coagulation associated with halloysite nanotubes. Compared to existing technologies, this invention improves the adsorption efficiency and maximum adsorption capacity of the microsphere adsorbent while ensuring adsorption safety.

[0035] In the preparation method of the microsphere adsorbent, a core with radial channels is first prepared by pre-freezing and then carbonized to ensure the mechanical properties of the core. Then, a low-viscosity slurry is immersed into the core, and the pre-freezing process is repeated, causing the cellulose to adhere to the inner wall of the radial channels, thus covering the exposed halloysite nanotubes. Additionally, a high-viscosity slurry is used to cover the surface of the core to prevent the slurry from entering the radial channels. Under gradient heating carbonization, the fibers on the inner wall of the radial channels and the surface of the core carbonize into a sponge-like pore structure. The reaction process is simple, can achieve complete coverage of halloysite nanotubes, and can form a gradient pore size, which is beneficial for improving adsorption efficiency and adsorption capacity.

[0036] The proportion of nanocellulose (CNF) in the second precursor solution and the first precursor solution is relatively higher than that of hydroxypropyl methylcellulose (HPMC). After carbonization, it helps to provide mechanical strength for the radial channels in the core and prevents the radial channels from collapsing during repeated adsorption and desorption.

[0037] The total amount of cellulose in the second precursor solution is lower than that in the first and third precursor solutions. This is partly to facilitate impregnation with the second precursor solution, and partly to form relatively large sponge-like channels. Compared to the smaller sponge-like channels in the shell, this has a diameter-expanding effect, thereby improving adsorption efficiency. Attached Figure Description

[0038] Figure 1 A model diagram of the blood purification microsphere adsorbent prepared according to an embodiment of the present invention;

[0039] Figure 2 for Figure 1 Enlarged diagram of area A in the middle.

[0040] [Explanation of Labels in the Attached Image]

[0041] 1: Core; 11: Radial channels;

[0042] 2: Shell;

[0043] 3: Protective layer;

[0044] 4: Halloysite nanotubes. Detailed Implementation

[0045] To better explain and facilitate understanding of the present invention, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0046] To better understand the above technical solutions, exemplary embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. Although exemplary embodiments of the present invention are shown in the drawings, it should be understood that the present invention can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that the present invention can be understood more clearly and thoroughly, and that the scope of the present invention can be fully conveyed to those skilled in the art.

[0047] Example 1

[0048] Reference Figure 1 and Figure 2 This embodiment provides a method for preparing a blood purification microsphere adsorbent, comprising the following steps:

[0049] (1) Preparation of the first precursor solution formulation: 4.0 g of nanocellulose (CNF), 2.0 g of hydroxypropyl methylcellulose (HPMC), 1.0 g of halloysite nanotubes, 4.0 g of 1-ethyl-3-methylimidazolium acetate (solvent), 0.2 g of polyethylene glycol (dispersant), and 12.0 g of mixed solvent (water:ethanol=7:3); the above materials were stirred at 70 °C until completely dissolved and uniformly dispersed; cooled to room temperature to obtain the first precursor solution.

[0050] A first-layer precursor solution with high viscosity is formed, which is suitable for generating a radial porous structure.

[0051] (2) Drop addition and pre-freezing operation: The first precursor solution was added dropwise into liquid nitrogen at a rate of 0.5-1 drops / s using a micro-injection pump; the pre-freezing time was 2 minutes; first precursor microspheres with an average particle size of 300-400 μm were formed. A radial pore structure was formed with an average pore size of 5 μm.

[0052] (3) Freeze-drying and carbonization process: The first precursor microspheres were transferred to a freeze dryer; the freeze-drying temperature was set to -50℃ and the time was 96 hours; then, the freeze-dried first precursor microspheres were carbonized in an argon atmosphere at a carbonization temperature of 700℃ and a carbonization time of 5 hours to obtain the first microsphere (core 1).

[0053] (4) Formulation for preparing the second precursor solution: 2.0 g of nanocellulose (CNF), 1.0 g of hydroxypropyl methylcellulose (HPMC), 3.0 g of N-methylmorpholine-N-oxide (NMMO) (solvent), 0.1 g of polyethylene glycol (PEG-400) (dispersant), and 16.0 g of deionized water; the above materials were stirred at 70 °C until completely dissolved and uniformly dispersed; the solution was cooled to room temperature to obtain the second precursor solution;

[0054] (5) Impregnation and freezing operations: The first microspheres are added to the second precursor solution, and the mixture is placed in a vacuum environment of -30 to -50 kPa for 10-15 minutes to allow the second precursor solution to fully impregnate the radial pore structure; then the impregnated first microspheres are taken out, placed in liquid nitrogen, and dispersed by microwave vibration, and pre-frozen for 2 minutes. The second precursor solution is used to further coat the exposed halloysite nanotubes 4 to form a protective layer 3.

[0055] (6) Re-freeze drying operation: Place the pre-frozen second microspheres in a freeze dryer, freeze dry at -50℃ for 72-96 hours to obtain the dried second microspheres.

[0056] (7) Preparation of the third precursor solution formulation: 2.0 g of nanocellulose (CNF), 4.0 g of hydroxypropyl methylcellulose (HPMC), 3.0 g of N-methylmorpholine-N-oxide (NMMO), 0.1 g of polyethylene glycol (PEG-400), and 15.0 g of deionized water; heat the above materials to 70°C and stir until completely dissolved to obtain the third precursor solution. Adjust the viscosity to a suitable level for coating (about 200-500 mPa·s) and cool for later use.

[0057] Increasing the proportion of HPMC in cellulose and using water as a solvent can create a finer microporous structure. A third precursor solution is used to form shell 2.

[0058] (8) Secondary coating and refreezing and lyophilization: The dried second microspheres obtained in step (6) are immersed in the third precursor solution and left to stand for 10 minutes to fully coat the surface; then the immersed second microspheres are taken out, placed in liquid nitrogen, and dispersed by microwave vibration. After prefreezing for 1 minute, the lyophilization operation step (6) is repeated to prepare the third microspheres.

[0059] Increasing the proportion of HPMC in cellulose in the third precursor solution helps improve the hydrophilicity and biocompatibility of the adsorbent surface, facilitating initial compatibility between the adsorbent and blood. Furthermore, using water as a solvent reduces the pre-freezing time, resulting in a finer microporous structure that prevents large protein molecules from entering and clogging the radial channels in the core, thus ensuring adsorption efficiency.

[0060] (9) Gradient heating carbonization operation: The third microsphere was placed in a tube furnace and carbonized under an argon protective atmosphere: Stage 1: The temperature was increased from room temperature to 200℃ at 1℃ / min and held for 2 hours; Stage 2: The temperature was increased to 700℃ at 3℃ / min and held for 5 hours, then naturally cooled to room temperature to obtain the final composite microsphere adsorbent. Gradient heating carbonization is beneficial to improving porosity and increasing specific surface area.

[0061] Example 2

[0062] This embodiment provides a method for preparing a blood purification microsphere adsorbent, including the following steps:

[0063] (1) Preparation of the first precursor solution formulation: 8.0 g microcrystalline cellulose, 2.0 g halloysite nanotubes, 5.0 g 1-ethyl-3-methylimidazolium acetate (solvent), 0.5 g polysorbate (dispersant), and 15.0 g solvent water; the above materials are stirred at 70 °C until completely dissolved and uniformly dispersed; cooled to room temperature to obtain the first precursor solution.

[0064] (2) Drop addition molding and pre-freezing operation: The first precursor solution is added dropwise into liquid nitrogen at a rate of 0.5-1 drops / s using a micro-injection pump; the pre-freezing time is 3 minutes; first precursor microspheres with an average particle size of 300-400 μm are formed. A radial pore structure is formed with an average pore size of 5 μm.

[0065] (3) Freeze-drying and carbonization process: The first precursor microspheres are transferred to a freeze dryer; the freeze-drying temperature is set to -40℃ and the time is 100 hours; then, the freeze-dried first precursor microspheres are carbonized in an argon atmosphere at a carbonization temperature of 400℃ and a carbonization time of 10 hours to obtain the first microsphere (core).

[0066] (4) Preparation of the second precursor solution formulation: 3.0 g of nanocellulose (CNF), 2.0 g of hydroxypropyl methylcellulose (HPMC), 5.0 g of N-methylmorpholine-N-oxide (NMMO) (solvent), 0.2 g of polyethylene glycol (PEG-400) (dispersant), and 20.0 g of deionized water; stir the above materials at 70 °C until completely dissolved and uniformly dispersed; cool to room temperature to obtain the second precursor solution.

[0067] (5) Impregnation and freezing operation: Add the first microsphere to the second precursor solution, place the mixture in a vacuum environment of -30 to -50 kPa for 10-15 minutes to allow the second precursor solution to fully impregnate the radial pore structure; then take out the impregnated first microsphere, place it in liquid nitrogen, disperse the first microsphere by microwave vibration, and pre-freeze for 3 minutes.

[0068] (6) Re-freeze drying operation: Place the pre-frozen second microspheres in a freeze dryer, freeze dry at -50℃ for 72-96 hours to obtain the dried second microspheres.

[0069] (7) Preparation of the third precursor solution formulation: 4.0 g of nanocellulose (CNF), 6.0 g of hydroxypropyl methylcellulose (HPMC), 5.0 g of N-methylmorpholine-N-oxide (NMMO), 0.1 g of polyethylene glycol (PEG-400), and 15.0 g of deionized water; heat the above materials to 70°C and stir until completely dissolved to obtain the third precursor solution. Adjust the viscosity to a suitable level for coating (about 200-500 mPa·s) and cool for later use.

[0070] (8) Secondary coating and re-freezing and lyophilization: The dried second microspheres obtained in step (6) are immersed in the third precursor solution and left to stand for 10 minutes to fully coat the surface; then the immersed second microspheres are taken out, placed in liquid nitrogen, and dispersed by microwave vibration. After pre-freezing for 1 minute, the lyophilization operation step (6) is repeated to prepare the third microspheres.

[0071] (9) Gradient heating carbonization operation: The third microsphere was placed in a tube furnace and carbonized under an argon protective atmosphere: Stage 1: The temperature was increased from room temperature to 300℃ at 2℃ / min and held for 1h; Stage 2: The temperature was increased to 800℃ at 4℃ / min and held for 4h, then naturally cooled to room temperature to obtain the final composite microsphere adsorbent. Gradient heating carbonization is beneficial to improving porosity and increasing specific surface area.

[0072] Comparative Example 1

[0073] This comparative example provides a method for preparing a blood purification microsphere adsorbent, which differs from Example 1 in that steps (4) to (10) are omitted.

[0074] Comparative Example 2

[0075] This comparative example provides a method for preparing a blood purification microsphere adsorbent, which differs from Example 1 in that the second precursor solution in step (4) is replaced with the third precursor solution in step (7).

[0076] In addition, the pre-freezing time in step (8) is adjusted to 2 minutes.

[0077] Performance testing of composite microsphere adsorbent

[0078] 1. Preparation of the base solution to simulate blood solution: Use physiological saline (0.9% NaCl) or phosphate buffered saline (PBS, pH 7.4) as the base solvent; Added components: Add an appropriate amount of human serum albumin (BSA, 5% w / v) to simulate the plasma protein environment; Add heparin sodium (0.1% w / v) to prevent blood clotting.

[0079] Using the base solution as a solvent, prepare a solution containing 20 mg / L VB. 12 An adsorption solution containing 20 mg / L β2 microglobulin, 4 ng / ml parathyroid hormone, 550 pg / ml interleukin-6, and 35 mg / L creatinine.

[0080] 50 mg of the adsorbent prepared in the examples and comparative examples were placed in conical flasks, and 50 ml of the prepared adsorption solution was added. The flasks were then placed in a 37°C constant-temperature shaker for adsorption. After 1 h and 2 h of adsorption, the supernatant was collected to test the final concentration of the adsorbed substance, and the clearance rate of the corresponding substance was calculated. The test results are shown in Tables 1 and 2. VB12 and creatinine contents were quantitatively analyzed using high-performance liquid chromatography (HPLC); β2-microglobulin, parathyroid hormone, and interleukin-6 were quantitatively analyzed using an enzyme-linked immunosorbent assay (ELISA) kit.

[0081] 2. Biocompatibility testing

[0082] Blood compatibility test - hemolysis test: Freshly collected human erythrocyte suspension was diluted with physiological saline to a 2%-5% erythrocyte suspension (v / v), and mixed with the microsphere adsorbent prepared in the examples and comparative examples, respectively. The mixture was incubated at 37°C for 1 hour, with 10 replicates for each treatment. After centrifugation, the supernatant was collected, and the absorbance was measured at a wavelength of 540 nm. The average hemolysis rate was calculated, and the detection P-value was determined. The experimental results are shown in Table 3.

[0083] Coagulation time determination: The effects of the microsphere adsorbents prepared in the examples and comparative examples on the blood coagulation process were evaluated using activated partial thromboplastin time (APTT) and prothrombin time (PT) tests. The experimental results are shown in Table 3.

[0084] The cytotoxicity assay was performed using the MTT assay: hepatocytes were seeded in 96-well plates, and an appropriate amount of culture medium containing microsphere adsorbent was added to each well. After culturing for 24 hours, MTT (yellow tetrazolium salt) solution was added, and incubation continued for 4 hours. The supernatant was discarded, and DMSO was added to dissolve the crystallized product. The absorbance value at 570 nm was measured in each well to assess hepatocyte viability. The experimental results are shown in Table 3.

[0085] Table 1. Average removal rates of different substances by the composite microsphere adsorbent after 1 h of adsorption (P < 0.01)

[0086]

[0087] Table 2. Removal rates of different substances by the composite microsphere adsorbent after 2 hours of adsorption (P < 0.01)

[0088]

[0089] Table 3. Biocompatibility test results of composite microsphere adsorbent

[0090]

[0091] Referring to Tables 1 and 2, after 1 hour of adsorption, the average removal rates of different substances in Examples 1 and 2 were significantly higher than those in Comparative Examples 1 and 2, indicating that the examples exhibited better adsorption rates in the initial stage of adsorption. After 2 hours of adsorption, the average removal rates of different substances in Examples 1 and 2 were significantly higher than those in Comparative Examples 1 and 2, indicating that the examples had better removal effects. Example 1, as the optimal example, had the highest adsorption rate and removal rate.

[0092] Comparing Comparative Example 1 and Comparative Example 2, it can be seen that adding a protective layer and shell with sponge-like pores is beneficial to improving both the adsorption rate and the removal rate.

[0093] Compared with Comparative Example 2, Examples 1 and 2 show that setting sponge-like channels with different pore sizes is beneficial to improving the adsorption rate and adsorption amount of the adsorbent.

[0094] Referring to Table 3, Example 1, as the best example, showed significantly better biocompatibility than other examples and comparative examples in terms of hemolysis rate, cell viability, and clotting time fluctuation.

[0095] Compared with Examples 1 and 2, Comparative Example 1 showed significantly lower hemolysis rate and cell survival rate, but significantly higher clotting time fluctuation, indicating poorer biocompatibility.

[0096] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A blood purification microsphere adsorbent, characterized in that, The microsphere adsorbent includes a core and a shell covering the outside of the core; The core has radial channels with an average pore size of 2-10 μm; The shell has a first sponge-like channel with an average pore size of 0.1-0.5 μm; The inner wall surface of the radial channels is covered with a protective layer, and the protective layer has a second sponge-like pore with an average pore size of 0.5-2 μm; the protective layer is cellulose-derived carbon. The average pore diameter of the first sponge-like channel is smaller than the average pore diameter of the second sponge-like channel; The radial channels are surrounded by sheets containing halloysite nanotubes and cellulose-derived carbon coated on their surfaces.

2. The blood purification microsphere adsorbent as described in claim 1, characterized in that, The shell is cellulose-derived carbon with a thickness of 10-150 μm.

3. The blood purification microsphere adsorbent as described in claim 2, characterized in that, The diameter of the core is 20-400 μm.

4. The blood purification microsphere adsorbent as described in claim 1, characterized in that, The cellulose-derived char is obtained by carbonizing cellulose; The cellulose includes at least one of microcrystalline cellulose, nanocellulose, hydroxymethyl cellulose, cellulose ether, methylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, and carboxymethyl cellulose.

5. A method for preparing a blood purification microsphere adsorbent, characterized in that, Includes the following steps: S1. Preparation of the core: According to the first specified ratio, the solubilizer, cellulose, dispersant and halloysite nanotubes are dispersed in the solvent to obtain the first precursor solution; the first precursor solution is dropped into liquid nitrogen, and after pre-freezing, freeze-drying and carbonization, a core with radial channels is formed; the inner diameter of the halloysite nanotubes is 10-30 nm. S2. Surface treatment of radial channels in the core: According to the second specified ratio, the solubilizer, cellulose and dispersant are dispersed in the solvent to obtain the second precursor solution; the second precursor solution is adsorbed into the core by the impregnation method, and the core impregnated with the second precursor solution is pre-frozen and freeze-dried to form the second microspheres. S3, Coating shell: Disperse the solubilizer, cellulose, and dispersant in a solvent according to the specified ratio to obtain the third precursor solution; The third precursor solution is coated on the surface of the second microsphere, and the second microsphere coated with the third precursor solution is pre-frozen, lyophilized, and carbonized by gradient heating to form a microsphere adsorbent. The concentration of cellulose in the second precursor solution is lower than that in the first and third precursor solutions.

6. The method for preparing the blood purification microsphere adsorbent as described in claim 5, characterized in that, In S1, the first specified ratio is the mass ratio of solubilizer, cellulose, dispersant, halloysite nanotubes, and solvent as 3-5:6-10:0.1-0.5:1-3:12-15.

7. The method for preparing the blood purification microsphere adsorbent as described in claim 6, characterized in that, In S2, the second specified ratio is the mass ratio of solubilizer, cellulose, dispersant and solvent as 3-5:3-5:0.1-0.5:16-20; In S3, the third specified ratio is the mass ratio of solubilizer, cellulose, dispersant and solvent as 3-5:6-10:0.1-0.5:12-15; The solubilizer is selected from one or more of N-methylmorpholine-N-oxide, 1-butyl-3-methylimidazolium chloride, and 1-ethyl-3-methylimidazolium acetate; The dispersant is selected from one or more of polyethylene glycol, polysorbate, and polyethylene glycol octylphenyl ether; The solvent is selected from one or more of water, ethanol, methanol, and dimethyl sulfoxide.

8. The method for preparing the blood purification microsphere adsorbent as described in claim 5, characterized in that, In S1, the carbonization temperature is 300-1500 ℃ and the carbonization time is 5-10 h.

9. The method for preparing the blood purification microsphere adsorbent as described in claim 5, characterized in that, In S3, the gradient heating carbonization includes two stages, which are carried out under an inert atmosphere: Stage 1: the temperature is increased from room temperature to 200-300℃ at a rate of 1-2℃ / min and held for 1-2 hours; Stage 2: the temperature is increased to 700-800℃ at a rate of 3-4℃ / min and held for 4-5 hours, and then cooled to room temperature.

10. The method for preparing the blood purification microsphere adsorbent as described in claim 5, characterized in that, In S1-S3, the pre-freezing time is 1-5 minutes, and the pre-freezing time in S1 and S2 is longer than the pre-freezing time in S3. In S1-S3, the freeze-drying temperature is -20 to -90 ℃, and the freeze-drying time is 12-120 h.

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