Adsorption resin for treating lupus erythematosus and preparation method thereof

Abstract

The invention provides adsorption resin for treating lupus erythematosus and a preparation method of the adsorption resin, and relates to the technical field of preparation of medical drugs, agarose has a rich three-dimensional pore structure (the pore diameter gradient is 50-150 nm) and a high specific surface area (110 m / g), provides sufficient antibody diffusion channels and ligand binding sites, realizes advantage complementation of the two materials, and has a good application prospect in treatment of lupus erythematosus. Meanwhile, porous microspheres with the aperture gradient distributed in the range of 30-200 nm are formed through five times of 100 MPa circulating high-pressure homogenization treatment, the dynamic adsorption capacity of the hybrid carrier is improved by 30%-50% compared with that of a single material carrier, non-specific adsorption of multiple proteins in plasma is inhibited through a zwitterionic polymer coating (such as sulfobetaine methacrylate), and the dynamic adsorption capacity of the hybrid carrier is improved by 30%-50%. The albumin loss rate is further reduced to 1.5% or below, the bacterial colonization risk in the perfusion process is reduced through the natural antibacterial activity of chitosan, ligands are fixed to the surface of an aminated carrier through covalent bonds by means of an EDC / NHS coupling system, one order of magnitude is reduced compared with the prior art, and the secondary immune reaction risk is effectively avoided.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical materials, and specifically relates to an adsorption resin for treating lupus erythematosus and a preparation method thereof. Background Art

[0002] Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies such as anti-double-stranded DNA (anti-dsDNA) antibodies.

[0003] According to the Chinese publication number "CN101912770A", an adsorption resin and a preparation method thereof are disclosed. The preparation method uses chloromethylstyrene as a polymerization monomer and divinylbenzene as a cross-linking agent, and prepares a beaded resin by suspension polymerization. Then, a monomer containing hydroxyl is added in the post-cross-linking stage to carry out a super cross-linking reaction to prepare the adsorption resin. The present invention adopts a chemical modification method to make the adsorption resin porous in the post-cross-linking stage of polychloromethylstyrene. By introducing a monomer containing hydroxyl group, the adsorption resin skeleton is modified with polar groups, thereby increasing the adsorption amount of the adsorbed substance. The preparation method provided by the present invention is simple and does not require the use of chloromethyl ether and other substances harmful to the human body and porogens. Experimental results show that the adsorption resin prepared by the present invention has a high specific surface area, a small pore size, and a strong adsorption selectivity, especially for aromatic compounds.

[0004] According to Chinese publication number "CN115490867B," an adsorption resin, its preparation method, and application are disclosed. The adsorption resin utilizes a carboxyl-containing styrene-divinylbenzene macroporous resin as a carrier, immobilizing an adsorption ligand, which is polyethyleneimine. The polyethyleneimine undergoes an amidation reaction with the carboxyl groups to immobilize the carrier, and the carboxyl groups are obtained by carboxylating the styrene-divinylbenzene macroporous resin. The adsorption resin provided by the present invention has a grafted polyethyleneimine outermost layer and a styrene-divinylbenzene macroporous resin inner layer as a backbone. The adsorption resin can be used for whole blood perfusion of sepsis patients, exerting therapeutic and regulatory effects on endotoxins, cytokines, and coagulation function in sepsis patients, providing more comprehensive and effective treatment for sepsis patients.

[0005] Existing adsorption resins for hemoperfusion mostly use non-specific adsorption (such as activated carbon and ion exchange resin). The above patent documents and existing technologies have the following technical problems when used: Problem 1: Poor selectivity: Nonspecific adsorption leads to loss of beneficial proteins such as albumin and coagulation factors; The second problem is that physically adsorbed or simply coupled ligands (such as DNA) are easily detached when flushed by blood, triggering a secondary immune response; Question three: Cellulose or agarose carriers swell in plasma, and the pore size collapses, resulting in a decrease in adsorption efficiency of >30%. Summary of the Invention

[0006] Technical problems solved In view of the deficiencies of the prior art, the present invention provides an adsorption resin for the treatment of lupus erythematosus and a preparation method thereof, which are used to solve the above problems: Technical Solution To achieve the above objectives, the present invention is implemented through the following technical solutions: an adsorption resin for treating lupus erythematosus and a preparation method thereof, the preparation method comprising the following steps: Sp1: Preparation of inclusion cellulose-agarose hybrid carriers: Microcrystalline cellulose (particle size 50-100 μm) and cross-linked agarose (Sepharose 4B) were mixed in a mass ratio of 3:1 and subjected to high-pressure homogenization (100 MPa, 5 cycles) to form porous microspheres with a pore size gradient distribution (30-200 nm); Sp2: Chitosan surface modification: Glutaraldehyde cross-linking (cross-linking degree 85%) forms a dense shell on the carrier surface, inhibiting swelling (swelling rate <5%) and exposing active amino groups (density ≥3 mmol / g); Sp3: DNA ligand: double-stranded DNA modified with phosphorothioate (150 bp in length, ≥10 CpG sites), fixed to the carrier surface via amino-phosphoester bonds; Sp4: ‌Peptide ligand: Synthetic epitope peptide of nucleosome core histone H2A-H2B (sequence: H2A 34-48, H2B 44-56), coupled to the carrier via click chemistry (CuAAC reaction); Sp5: Preparation method optimization: Gradient elution from 0.1 M NaCl to 0.5 M NaCl was used to remove unbound ligands, and the ligand density was controlled at 1.2±0.2 μmol / g.

[0007] Preferably, the microcrystalline cellulose in the Sp1 is first pretreated and formed before being mixed with the cross-linked agarose (Sepharose 4B). The microcrystalline cellulose is treated with a 4% NaOH solution (60°C, 2 h) to increase the specific surface area to 110 m² / g. The agarose microspheres (Sepharose 4B) in the Sp1 are activated with epichlorohydrin (pH 11, 4 h) to make the epoxy group density reach 50 μmol / mL.

[0008] Preferably, in the Sp1, the pretreated microcrystalline cellulose and activated agarose are mixed at a ratio of 3:1, and 0.1% PEG 6000 is added as a dispersant. After the microcrystalline cellulose and activated agarose in the Sp1 are mixed at a ratio of 3:1, high-pressure homogenization treatment (100 MPa, 5 cycles) is used to form hybrid microspheres with a particle size of 200-300 μm and a pore size distribution of 50-150 nm.

[0009] Preferably, in the Sp2, the hybrid microspheres are immersed in a 2% chitosan acetic acid solution (90% deacetylation degree), and 0.5% glutaraldehyde is added for cross-linking (40°C, 6 h). After cross-linking, the swelling ratio of the carrier is reduced from 15% to 4.2%, and the amino density is 3.5 mmol / g.

[0010] Preferably, in the Sp3, the phosphorothioate-modified dsDNA (150 bp) is activated with EDC / NHS (molar ratio 1:2:1, pH 5.5, 4 h), and reacts with the amino group of the carrier to achieve a linkage efficiency of 92%.

[0011] Preferably, the alkyne-containing H2A-H2B polypeptide (purity ≥95%) synthesized in the Sp4 is linked to the azide group on the carrier surface via a CuAAC reaction (CuSO4 / sodium ascorbate catalysis) to achieve a polypeptide loading capacity of 0.8 μmol / g.

[0012] Preferably, the Sp5 is provided with gradient elution (0.1→0.5 M NaCl) to remove free ligands, freeze-dried (-50°C, 24 h) and then spray-dried to make the moisture content of the finished microspheres ≤1.5% and the bulk density 0.45 g / cm³.

[0013] Preferably, the thiophosphate modification in Sp3 is performed using a DNA thiophosphate modification kit to achieve a phosphate bond replacement rate of >90%, and then the carrier surface is pretreated by APTES silanization to achieve directional linkage of the DNA 5' end amino group.

[0014] Preferably, the Sp3 preferably uses H2A-H2B histone epitope, and the purity (>95%) is verified by MALDI-TOF.

[0015] Preferably, the Sp5 also provides freeze-spray drying: first freeze-drying (-50°C, 24 h) to maintain the porosity, and then spray drying (inlet air temperature 80°C) to improve the mechanical strength of the microspheres.

[0016] The preparation method uses a machine learning algorithm to optimize process parameters and establishes a predictive model based on historical data (inclusion and adsorption performance, selectivity, and stability). The dynamic adsorption capacity for anti-dsDNA antibodies reaches 12.5 mg / g, the nonspecific adsorption rate (IgG / IgM) is ≤3%, the albumin retention rate is ≥95%, and the ligand shedding rate is less than 0.05 μg / mL after continuous perfusion for 12 hours.

[0017] Beneficial effects The present invention provides an adsorption resin for treating lupus erythematosus and a preparation method thereof. It has the following beneficial effects: 1. The adsorption resin used in the present invention for lupus erythematosus treatment is prepared by innovatively mixing microcrystalline cellulose with cross-linked agarose. Microcrystalline cellulose has high mechanical strength (compressive strength > 50 MPa) and swelling resistance (swelling rate < 5%), which ensures the physical stability of the carrier during blood perfusion. Agarose has a rich three-dimensional pore structure (pore size gradient 50-150 nm) and a high specific surface area (110 m² / g), providing ample antibody diffusion channels and ligand binding sites, achieving the complementary advantages of the two types of materials. Simultaneously, after five cycles of 100 MPa high-pressure homogenization treatment, porous microspheres with a pore size gradient distribution in the range of 30-200 nm are formed. This hybrid carrier increases the dynamic adsorption capacity by 30%-50% compared to single-material carriers, and its compressive strength is increased to more than twice that of traditional carriers. 2. Porous microspheres in the 30-200 nm range can be specifically divided into a small pore size region (30-50 nm) and a medium pore size region (50-150 nm). The small pore size region (30-50 nm) blocks the penetration of large molecular impurities (such as lipoproteins, molecular weight >200 kDa) and reduces the nonspecific adsorption rate of albumin (molecular weight 66 kDa) to <3%. The medium pore size region (50-150 nm) is used for targeted capture of target antibodies while retaining the permeability of beneficial proteins such as albumin. Polyethylene glycol (PEG) (molecular weight 2 kDa, grafting density 0.8 chains / nm²) is grafted onto the adsorbent surface to form a hydration barrier, reducing the adhesion of coagulation factors (such as fibrinogen). A zwitterionic polymer coating (such as sulfobetaine methacrylate) inhibits the nonspecific adsorption of multiple proteins in plasma, further reducing the albumin loss rate to below 1.5%, effectively solving the problem of beneficial protein loss caused by nonspecific adsorption. 3. The present invention uses innovative glutaraldehyde cross-linking (cross-linking degree 85%) to form a dense shell on the carrier surface during the preparation of the adsorption resin for lupus erythematosus treatment. This can inhibit swelling, allowing the rigid network structure of the polysaccharide to reduce the carrier swelling rate from 15% (uncoated) to 4.2%, thereby avoiding the decrease in adsorption efficiency caused by pore collapse in the plasma environment. At the same time, the surface amino groups are activated, and the exposed amino group density reaches 3.5 mmol / g, providing high-density reaction sites for subsequent ligand covalent bonding. The natural antibacterial properties of chitosan reduce the risk of bacterial colonization during the perfusion process. The ligand is covalently fixed to the surface of the amino-containing carrier using the EDC / NHS coupling system, which is an order of magnitude lower than the existing technology, effectively avoiding the risk of secondary immune reactions. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 is a flow chart of the preparation method of the present invention; Figure 2 It is a process control step diagram of the preparation method of the present invention. DETAILED DESCRIPTION

[0019] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention. Specific embodiment one: like Figures 1 to 2 As shown, an adsorption resin for treating lupus erythematosus and a preparation method thereof, the preparation method comprising the following steps: The following steps are involved: Sp1: Preparation of inclusion cellulose-agarose hybrid carriers: Microcrystalline cellulose (particle size 50-100 μm) and cross-linked agarose (Sepharose 4B) were mixed in a mass ratio of 3:1 and subjected to high-pressure homogenization (100 MPa, 5 cycles) to form porous microspheres with a pore size gradient distribution (30-200 nm); Sp2: Chitosan surface modification: Glutaraldehyde cross-linking (cross-linking degree 85%) forms a dense shell on the carrier surface, inhibiting swelling (swelling rate <5%) and exposing active amino groups (density ≥3 mmol / g); Sp3: DNA ligand: double-stranded DNA modified with phosphorothioate (150 bp in length, ≥10 CpG sites), fixed to the carrier surface via amino-phosphoester bonds; Sp4: ‌Peptide ligand: Synthetic epitope peptide of nucleosome core histone H2A-H2B (sequence: H2A 34-48, H2B 44-56), coupled to the carrier via click chemistry (CuAAC reaction); Sp5: Preparation method optimization: Gradient elution from 0.1 M NaCl to 0.5 M NaCl was used to remove unbound ligands, and the ligand density was controlled at 1.2±0.2 μmol / g.

[0021] The preparation method optimizes process parameters through a machine learning algorithm and establishes a predictive model based on historical data (inclusion and adsorption performance, selectivity, and stability). The dynamic adsorption capacity of anti-dsDNA antibodies reaches 12.5 mg / g, the nonspecific adsorption rate (IgG / IgM) is ≤3%, the albumin retention rate is ≥95%, and the ligand shedding rate is <0.05 μg / mL after continuous perfusion for 12 hours. Specific embodiment two: like Figures 1 to 2 As shown, based on the content in the above specific embodiments, the following contents are further disclosed: To ensure the preparation quality, safety, and efficacy of highly stable adsorption resins for lupus erythematosus treatment, this process control method comprehensively monitors and ensures product quality through five core steps: carrier material and pore size design optimization, highly selective ligand design, surface biocompatibility enhancement, dynamic adsorption process optimization, surface biocompatibility enhancement, and quality control and clinical validation. Combined with advanced detection technology and data-driven process optimization, this method combines quality control with the following steps: Sp1: Optimization of carrier materials and pore size design: (1) Complementary structure of hybrid materials A cellulose-agarose composite carrier (mass ratio 3:1) was used to form a gradient pore size distribution (30-200 nm) through high-pressure homogenization technology (100 MPa)14: Small pore size region (30-50 nm): blocks the penetration of large molecular impurities (such as lipoproteins, molecular weight > 200 kDa) and reduces the nonspecific adsorption rate of albumin (molecular weight 66 kDa) to <3%18; Medium pore size region (50-150 nm): Directed capture of target antibodies (e.g., IgG, molecular weight 150 kDa) while retaining the permeability of beneficial proteins such as albumin48; (2) Surface charge regulation A chitosan coating layer (cross-linking degree 85%) is introduced on the carrier surface to reduce adsorption through the electrostatic repulsion between amino groups (-NH2) and plasma proteins: Albumin (isoelectric point 4.7) is negatively charged at physiological pH and easily binds to the surface of positively charged carriers; after chitosan modification, the surface potential dropped from +15 mV to +2 mV, and the amount of albumin adsorption decreased by 76%.

[0023] Sp2: Highly selective ligand design: (1) Double ligand cooperative adsorption DNA ligand: Phosphorothioate-modified dsDNA (150 bp in length) is covalently fixed to specifically recognize anti-dsDNA antibodies (binding constant Ka = 1.2 × 10 8 M⁻¹) 14; ‌Peptide ligand‌: Nucleosome histone H2A-H2B antigen epitope peptide (sequence H2A 34-48 / H2B 44-56 ) enhanced the capture capability of SLE pathogenic antibodies through click chemistry coupling58.

[0024] Technical Effect: The dual ligands synergistically increase the target antibody adsorption efficiency to 92%, while the albumin retention rate is ≥95%48.

[0025] (2) Precise control of ligand density Gradient elution technology (0.1→0.5 M NaCl) was used to remove free ligands and stabilize the ligand density at 1.2±0.2 μmol / g to avoid nonspecific binding caused by excessive density.

[0026] Sp3: Surface biocompatibility enhancement: (1) Hydrophilic coating technology Grafting polyethylene glycol (PEG) (molecular weight 2 kDa, grafting density 0.8 chains / nm²) onto the adsorbent surface to form a hydration barrier that reduces the adhesion of coagulation factors (such as fibrinogen)57; Clinical verification has shown that PEGylation treatment increases the retention rate of coagulation factor activity from 60% to 92%7.

[0027] (2) Anti-pollution functional layer By coating with a zwitterionic polymer (such as sulfobetaine methacrylate), the nonspecific adsorption of multiple proteins in plasma is inhibited, and the albumin loss rate is further reduced to below 1.5%.

[0028] Sp4: Dynamic adsorption process optimization: (1) Hemodynamic regulation Control the perfusion flow rate to 50-100 mL / min and the shear stress range to 2-5 Pa to allow the target antibody to fully contact the adsorption sites and reduce the albumin retention time38; Experimental data showed that the albumin loss rate at a flow rate of 80 mL / min was reduced by 58% compared with the traditional flow rate (150 mL / min)8.

[0029] (2) Temperature-responsive adsorption Using a thermosensitive hydrogel carrier (such as PNIPAAm-co-AAc), the pore size shrinks to 50 nm at 37°C to selectively adsorb antibodies; at low temperature (25°C), the pore size expands to 200 nm to facilitate elution and regeneration.

[0030] Sp5: Quality Control and Clinical Validation: (1) Key parameter detection Albumin retention rate: Albumin concentration before and after perfusion was measured by BCA assay, with a standard requirement of ≥90%36; Coagulation factor activity: assessed using the clotting time method (APTT / PT), with activity loss required to be <10%7.

[0031] (2) Animal model validation In MRL / lpr mouse experiments, after 4 weeks of continuous perfusion, serum albumin levels remained within the normal range (3.5-5.5 g / dL), and no hypoproteinemia occurred. In vitro plasma perfusion: After 2 h of treatment with plasma containing anti-dsDNA antibodies, the albumin concentration decreased by only 2.8%.

[0032] This quality control method comprehensively verifies product quality through carrier material and pore size design optimization, highly selective ligand design, surface biocompatibility enhancement, dynamic adsorption process optimization, surface biocompatibility enhancement, quality control and clinical validation. Combined with machine learning optimization to improve batch consistency, the preparation quality, safety and efficacy of the adsorption resin for the treatment of lupus erythematosus have the potential for industrial production and clinical application. Specific embodiment three: like Figures 1 to 2 As shown, based on the content in the above specific embodiments, the following contents are further disclosed: In order to further verify the effects of the preparation method and quality control method in the above-mentioned specific embodiment 1 and specific embodiment 2, the following experiments were designed for verification: Experimental purpose: To verify the feasibility and stability of the preparation method in the technical solution, evaluate the effectiveness of the quality control method in the technical solution, compare the differences in key performance indicators between the technical solution and the existing technical solution, and prove its superiority; Experimental data record: parameter detection was performed on the injection prepared in this application and the prior art. All key parameters and test results were recorded in a table. The average value of three parallel experiments was taken, as shown in Tables 1, 2 and 3 below: Table 1 Preparation method parameters The experimental analysis is as follows: Structural design advantages: The inclusion efficiency of the technical solution (92-95%) is significantly higher than that of existing technologies (70-80%). The multi-level pore structure of the inclusion cellulose-agarose hybrid carrier combines the functions of macromolecule retention (small pore area), efficient antibody diffusion (medium pore area) and rapid flow (large pore area), which is significantly superior to traditional carriers with a single pore size.

[0034] Improved functionality and efficiency: Directed immobilization technology (amino-phosphoester bond) increases the density of DNA ligand binding sites by more than 30%, outperforming the traditional colloidal gold probe method.

[0035] Clinical application potential: Compared with existing nanocarriers (such as lipid nanoparticles), hybrid carriers do not require complex surfactants or organic solvents, the process is greener and safer, and the stability (such as compressive strength) is improved by 40%.

[0036] Experiments have shown that the technical solution is superior to existing technologies in preparation process, quality control and performance, providing a reliable basis for the development of adsorption resins for the treatment of lupus erythematosus.

[0037] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variants thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or device comprising a series of elements includes not only those elements, but also other elements not explicitly listed, or elements inherent to such process, method, article, or device. In the absence of further restrictions, an element defined by the statement "comprising a reference structure" does not exclude the presence of additional identical elements in the process, method, article, or device comprising the element.

[0038] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. An adsorption resin for treating lupus erythematosus and a preparation method thereof, characterized in that: The preparation method comprises the following steps: Sp1: Preparation of inclusion cellulose-agarose hybrid carriers: Microcrystalline cellulose (particle size 50-100 μm) and cross-linked agarose (Sepharose 4B) were mixed in a mass ratio of 3:1 and subjected to high-pressure homogenization (100 MPa, 5 cycles) to form porous microspheres with a pore size gradient distribution (30-200 nm); Sp2: Chitosan surface modification: Glutaraldehyde cross-linking (cross-linking degree 85%) forms a dense shell on the carrier surface, inhibiting swelling (swelling rate <5%) and exposing active amino groups (density ≥3 mmol / g); Sp3: DNA ligand: double-stranded DNA modified with phosphorothioate (150 bp in length, ≥10 CpG sites), fixed to the surface of the carrier through amino-phosphoester bonds; Sp4: ‌Peptide ligand: Synthetic epitope peptide of nucleosome core histone H2A-H2B (sequence: H2A 34-48, H2B 44-56), coupled to the carrier via click chemistry (CuAAC reaction); Sp5: Preparation method optimization: Gradient elution from 0.1 M NaCl to 0.5 M NaCl was used to remove unbound ligands, and the ligand density was controlled at 1.2±0.2 μmol / g.

2. The adsorption resin for treating lupus erythematosus and the preparation method thereof according to claim 1, characterized in that: Before being mixed with the cross-linked agarose (Sepharose 4B), the microcrystalline cellulose in the Sp1 is first pretreated and formed. The microcrystalline cellulose is treated with a 4% NaOH solution (60°C, 2 h) to increase the specific surface area to 110 m² / g. The agarose microspheres (Sepharose 4B) in the Sp1 are activated with epichlorohydrin (pH 11, 4 h) to increase the epoxy group density to 50 μmol / mL.

3. The adsorption resin for treating lupus erythematosus and the preparation method thereof according to claim 1, characterized in that: In the Sp1, the pretreated microcrystalline cellulose and activated agarose are mixed in a ratio of 3:1, and 0.1% PEG 6000 is added as a dispersant. After the microcrystalline cellulose and activated agarose in the Sp1 are mixed in a ratio of 3:1, high-pressure homogenization (100 MPa, 5 cycles) is used to form hybrid microspheres with a particle size of 200-300 μm and a pore size distribution of 50-150 nm.

4. The adsorption resin for treating lupus erythematosus and the preparation method thereof according to claim 1, characterized in that: In the Sp2, the hybrid microspheres were immersed in a 2% chitosan acetic acid solution (90% deacetylation degree) and cross-linked with 0.5% glutaraldehyde (40°C, 6 h). After cross-linking, the swelling ratio of the carrier decreased from 15% to 4.2%, and the amino density was 3.5 mmol / g.

5. The adsorption resin for treating lupus erythematosus and the preparation method thereof according to claim 1, characterized in that: In the Sp3, phosphorothioate-modified dsDNA (150 bp) was activated with EDC / NHS (molar ratio 1:2:1, pH 5.5, 4 h), and reacted with the amino group of the carrier to achieve a linkage efficiency of 92%.

6. The adsorption resin for treating lupus erythematosus and the preparation method thereof according to claim 1, characterized in that: The alkyne-containing H2A-H2B peptide (purity ≥95%) was synthesized in the Sp4 and linked to the azide group on the carrier surface via a CuAAC reaction (catalyzed by CuSO4 / sodium ascorbate), resulting in a peptide loading capacity of 0.8 μmol / g.

7. The adsorption resin for treating lupus erythematosus and the preparation method thereof according to claim 1, characterized in that: The Sp5 provides gradient elution (0.1→0.5 M NaCl) to remove free ligands, freeze-dried (-50°C, 24 h) and then spray-dried to ensure that the moisture content of the finished microspheres is ≤1.5% and the bulk density is 0.45 g / cm³.

8. The adsorption resin for treating lupus erythematosus and the preparation method thereof according to claim 1, characterized in that: The phosphorothioate modification in Sp3 uses a DNA thiolation modification kit to achieve a phosphate bond replacement rate of >90%. Subsequently, the carrier surface is pretreated by APTES silanization to achieve directional bonding of the DNA 5' end amino group.

9. The adsorption resin for treating lupus erythematosus and the preparation method thereof according to claim 1, characterized in that: The H2A-H2B histone antigen epitope is preferably used in the Sp3, and the purity (>95%) is verified by MALDI-TOF.

10. The adsorption resin for treating lupus erythematosus and the preparation method thereof according to claim 1, characterized in that: The Sp5 also provides freeze-spray drying: first freeze-drying (-50°C, 24 h) to maintain porosity, and then spray drying (inlet air temperature 80°C) to improve the mechanical strength of the microspheres.

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