Magnetic composite adsorbent for hemoperfusion, and preparation method and application thereof

Abstract

The application relates to the field of medical devices, and particularly discloses a magnetic composite adsorbent for blood perfusion as well as a preparation method and application thereof. The magnetic composite adsorbent takes magnetic nanoparticles as a core, is connected with endotoxin affinity peptides through a crosslinking agent, and forms a composite adsorbent; the amino acid sequence of the endotoxin affinity peptide is Lys-His-Arg-Asp-Cys-Lys-Trp-Leu-Lys-Arg-Cys-Trp. The magnetic composite adsorbent has specific affinity for endotoxin, the endotoxin affinity peptide is fixed on the surface of the magnetic nanoparticles through a chemical bond, the adsorbent can be recycled through magnetic separation in the blood perfusion process, the endotoxin affinity peptide is not easy to fall off and stay in the blood, and therefore the magnetic composite adsorbent is safer and more efficient.

Description

Technical Field

[0001] This application relates to the field of medical devices, and more specifically, to a magnetic composite adsorbent for blood perfusion, its preparation method, and its application. Background Technology

[0002] Hemoperfusion (HP) is a blood purification technique that involves introducing a patient's blood into a perfusion device containing a solid adsorbent. Through adsorption, it removes exogenous or endogenous toxins, drugs, or metabolic waste products from the blood that cannot be removed by dialysis. It is primarily used to treat drug and toxin poisoning and can also be used in conjunction with hemodialysis to remove large molecular toxins from patients undergoing maintenance dialysis for chronic renal failure. The basic principle of hemoperfusion is adsorption. The perfusion column consists of an adsorbent and a coating material; the adsorbent has the ability to adsorb dissolved and colloidal substances in the liquid.

[0003] Polymyxin B is an antibiotic that inhibits various negative-positive bacteria, particularly those resistant to other antibiotics. In existing technologies, polymyxin B is often adsorbed and immobilized onto the amino groups of α-chloroacetamide-methylpolystyrene fibers to form polymyxin B-fixed fiber hemoperfusion devices. Polymyxin B has a high affinity for the lipid A portion of lipopolysaccharide, thus enabling it to adsorb and remove endotoxins from the blood. However, in this method, polymyxin B is adsorbed and immobilized on the fibers, and may detach during perfusion, remaining in the blood. Furthermore, due to its poor stability and strong nephrotoxicity and neurotoxicity, polymyxin B poses significant safety risks in practical applications. Summary of the Invention

[0004] To improve the adsorption efficiency of adsorbents for endotoxins in hemoperfusion and reduce toxicity and potential risks, this application provides a magnetic composite adsorbent for hemoperfusion, its preparation method, and its application.

[0005] The technical solution adopted in this application is as follows:

[0006] In a first aspect, a magnetic composite adsorbent for blood perfusion, wherein the magnetic composite adsorbent has magnetic nanoparticles as its core and is linked to endotoxin affinity peptides through a cross-linking agent to form a composite adsorbent;

[0007] The amino acid sequence of the endotoxin affinity peptide is as follows:

[0008] Lys-His-Arg-Asp-Cys-Lys-Trp-Leu-Lys-Arg-Cys-Trp.

[0009] The magnetic composite adsorbent provided by the above technical solution uses magnetic nanoparticles as the core carrier and is linked to endotoxin affinity peptides of a specific sequence via chemical bonds, forming a composite adsorbent with high affinity, high specificity, and high detoxification activity for the target endotoxin. This endotoxin affinity peptide was obtained by screening using phage surface display technology, based on E. coli endotoxin as a model, and exhibits specific affinity for endotoxins. This may be because the basic amino acids in the peptide chain of the endotoxin affinity peptide can form ionic interactions with the phosphate groups of the endotoxin, and the disulfide bonds formed between the two cysteine ​​residues in the peptide chain create a special entangled structure, thus exhibiting extremely strong specific adsorption capacity for endotoxins. In the synthesis of the above magnetic composite adsorbent, the endotoxin affinity peptide of the above sequence is artificially synthesized and then immobilized on magnetic nanoparticles.

[0010] Compared to existing hemoperfusion adsorbents that use polymyxin B as the adsorbent, this magnetic composite adsorbent has a comparable ability to purify endotoxins in the blood, but does not produce nephrotoxicity or neurotoxicity. Furthermore, since the endotoxin affinity peptides are fixed to the surface of magnetic nanoparticles by chemical bonds, the adsorbent can be easily recovered through magnetic separation during hemoperfusion, and the endotoxin affinity peptides are not easily detached and remain in the blood, thus making it safer and more efficient.

[0011] Furthermore, the magnetic nanoparticles mentioned above are Fe3O4 particles, and the particle size of the magnetic nanoparticles is 100-300 nm.

[0012] Magnetic nanoparticles of this size possess the advantages of large specific surface area, strong magnetic responsiveness, good biocompatibility, and easy adsorption, facilitating magnetic separation during blood perfusion. Preferably, the particle size of the magnetic nanoparticles is 200-300 nm.

[0013] Furthermore, the aforementioned endotoxin affinity peptide is a modified endotoxin affinity peptide that has been modified by chondroitin sulfate.

[0014] Furthermore, the preparation method of the above-mentioned modified endotoxin affinity peptide includes:

[0015] The endotoxin affinity peptide was dissolved in ethanol to obtain an endotoxin affinity peptide solution.

[0016] Chondroitin sulfate and dicyclohexylcarbodiimide were added to the endotoxin affinity peptide solution, and a condensation reaction was carried out at 30-40°C to obtain chondroitin sulfate-modified endotoxin affinity peptide.

[0017] In a preferred embodiment of this application, chondroitin sulfate is used to chemically modify the endotoxin affinity peptide with the specific sequence described above, so as to improve the stability and biocompatibility of the endotoxin affinity peptide, thereby further enhancing its safety and prolonging the circulation time of this magnetic composite adsorbent during blood perfusion.

[0018] Chondroitin sulfate is a glycosaminoglycan with multiple hydroxyl and carboxyl functional groups. Under the action of dicyclohexylcarbodiimide, it can undergo a condensation reaction with the aforementioned endotoxin affinity peptide with a specific sequence, forming an amide bond or ester bond, thereby linking chondroitin sulfate to the endotoxin affinity peptide. Experiments show that the affinity of the endotoxin affinity peptide modified with chondroitin sulfate for endotoxin is not reduced, indicating that chondroitin sulfate does not affect the active site of the endotoxin affinity peptide.

[0019] Further, the molar ratio of the endotoxin affinity peptide to chondroitin sulfate is 1:1.3-1.5; preferably, the molar ratio of the endotoxin affinity peptide to chondroitin sulfate is 1:1.2-1.4.

[0020] Furthermore, the condensation reaction takes 2-4 hours, preferably 2.5-3.5 hours.

[0021] Secondly, this application provides a method for preparing the above-mentioned magnetic composite adsorbent, comprising:

[0022] Magnetic nanoparticles were placed in a 60-80 vol% ethanol solution, ultrasonically dispersed, and then a tetramethylsilane hydrochloric acid solution was added. After reacting with an inorganic alkali solution at 50-60℃ for 2-3 hours, the mixture was washed with PBS buffer solution to obtain magnetic nanoparticles coated with silica.

[0023] The silica-coated magnetic nanoparticles were resuspended in PBS buffer solution, and crosslinking agents EDC and NHS were added and stirred for 1-2 hours. Then, the endotoxin affinity peptide was added and incubated at room temperature for 30-60 minutes to obtain the magnetic composite adsorbent.

[0024] Furthermore, the mass ratio of the aforementioned silica-coated magnetic nanoparticles to the endotoxin affinity peptide is 20-30:1.

[0025] Furthermore, the aforementioned endotoxin affinity peptide is a modified endotoxin affinity peptide after being modified with chondroitin sulfate, and the preparation method of the modified endotoxin affinity peptide includes:

[0026] The endotoxin affinity peptide was dissolved in ethanol to obtain an endotoxin affinity peptide solution.

[0027] Chondroitin sulfate and dicyclohexylcarbodiimide were added to the endotoxin affinity peptide solution, and a condensation reaction was carried out at 30-40°C to obtain chondroitin sulfate-modified endotoxin affinity peptide.

[0028] Thirdly, this application provides an application of the above-mentioned magnetic composite adsorbent in the preparation of a blood perfusion device.

[0029] In summary, this application has the following beneficial effects:

[0030] The magnetic composite adsorbent provided in this application uses magnetic nanoparticles as the core carrier, which are linked to endotoxin affinity peptides with specific sequences via chemical bonds, forming a composite adsorbent with high affinity, high specificity, and high detoxification activity for the target endotoxin. This endotoxin affinity peptide was obtained by screening using phage surface display technology, based on E. coli endotoxin as a model, demonstrating its specific affinity for endotoxins. Furthermore, because the endotoxin affinity peptide is fixed to the surface of the magnetic nanoparticles via chemical bonds, the adsorbent can be easily recovered through magnetic separation during blood perfusion, and the endotoxin affinity peptide is less likely to detach and remain in the blood, thus making it safer and more efficient. Detailed Implementation

[0031] The embodiments of the present invention will be described in detail below with reference to the examples. However, those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention. Specific conditions not specified in the examples shall be carried out according to conventional conditions or conditions recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0032] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0033] The endotoxin affinity peptide in this application was obtained through phage display technology and synthesized artificially after sequencing. The endotoxin affinity peptide is 12 amino acids long, with the specific amino acid sequence: Lys-His-Arg-Asp-Cys-Lys-Trp-Leu-Lys-Arg-Cys-Trp (SEQ ID.01).

[0034] Preparation examples of raw materials and / or intermediates

[0035] Preparation Example 1

[0036] This preparation example provides a modified endotoxin affinity peptide, the preparation method of which includes:

[0037] 1. A specific endotoxin affinity peptide was synthesized using a solid-phase synthesis method, the sequence of which is shown in SEQ ID.01. This step was performed by a biotechnology company.

[0038] 2. Dissolve 200g of endotoxin affinity peptide with a purity of 99% or higher in 100mL of ethanol to obtain an endotoxin affinity peptide solution with a concentration of 2mg / mL.

[0039] 3. Dissolve chondroitin sulfate in 20 ml of water, then add it to the endotoxin affinity peptide solution, and then add the condensing agent dicyclohexylcarbodiimide to form a mixed reaction solution. In the mixed reaction solution, the molar ratio of endotoxin affinity peptide, chondroitin sulfate and dicyclohexylcarbodiimide is 1:1.4:0.2.

[0040] 4. After reacting the mixed reaction solution in a water bath at 35°C for 3 hours, wash it sequentially with ethanol and PBS buffer solution to obtain chondroitin sulfate-modified toxin affinity peptide.

[0041] Preparation Example 2

[0042] This preparation example provides a modified endotoxin affinity peptide, the preparation method of which differs from that of Preparation Example 1 in that the molar ratio of the endotoxin affinity peptide to chondroitin sulfate and dicyclohexylcarbodiimide is 1:1.3:0.2.

[0043] Preparation Example 3

[0044] This preparation example provides a modified endotoxin affinity peptide, the preparation method of which differs from that of Preparation Example 1 in that the molar ratio of the endotoxin affinity peptide to chondroitin sulfate and dicyclohexylcarbodiimide is 1:1.5:0.2.

[0045] Preparation Example 4

[0046] This preparation example provides a modified endotoxin affinity peptide, the preparation method of which differs from that of Preparation Example 1 in that: in the final step, the mixed reaction solution is placed in a water bath at 30°C for 4 hours.

[0047] Preparation Example 5

[0048] This preparation example provides a modified endotoxin affinity peptide, the preparation method of which differs from that of Preparation Example 1 in that: in the final step, the mixed reaction solution is placed in a water bath at 40°C for 2 hours.

[0049] Preparation Example 6

[0050] This preparation example provides a modified endotoxin affinity peptide, the preparation method of which differs from that of Preparation Example 1 in that an equimolar amount of hyaluronic acid is used instead of chondroitin sulfate.

[0051] Example

[0052] Example 1

[0053] This embodiment provides a magnetic composite adsorbent for hemoperfusion, the preparation method of which includes:

[0054] 1. Disperse 100g of magnetic nanoparticles (purchased from Hangzhou Jikang New Materials Co., Ltd., 200-300nm) in a pure ethanol solution, ultrasonically disperse, wash, and then resuspend in 200mL of 70vol% ethanol solution.

[0055] 2. Dissolve 18g of tetramethylsilane in hydrochloric acid solution to obtain a 0.1mol / L tetramethylsilane solution. Add this solution to the ethanol dispersion of magnetic nanoparticles obtained in step (1), then add 4mL of ammonia water. After reacting at 55℃ for 3h, wash with ethanol, water and PBS buffer solution (pH 7.4) in sequence to obtain magnetic nanoparticles coated with silica.

[0056] 3. 50 g of silica-coated magnetic nanoparticles were resuspended in PBS buffer solution, and 0.2 mol of crosslinking agent EDC and 0.2 mol of NHS were added. The mixture was stirred for 1 h to obtain activated magnetic nanoparticles. Then, 2 g of endotoxin affinity peptide was added and incubated at room temperature for 45 min. Subsequently, 0.1 wt% BSA was added for blocking for 20 min. Finally, the mixture was magnetically separated and washed with PBS buffer solution to obtain a magnetic composite adsorbent.

[0057] Example 2

[0058] This embodiment provides a magnetic composite adsorbent for hemoperfusion, the preparation method of which includes:

[0059] 1. Disperse 100g of magnetic nanoparticles (purchased from Hangzhou Jikang New Materials Co., Ltd., 200-300nm) in a pure ethanol solution, ultrasonically disperse, wash, and then resuspend in 200mL of 60-80vol% ethanol solution.

[0060] 2. Dissolve 18g of tetramethylsilane in hydrochloric acid solution to obtain a 0.1mol / L tetramethylsilane solution. Add this solution to the ethanol dispersion of magnetic nanoparticles obtained in step (1), and then add 2mL of ammonia water. React at 50-60℃ for 2-3h, and then wash with ethanol, water and PBS buffer solution (pH 7.4) in sequence to obtain magnetic nanoparticles coated with silica; 3. Resuspend 40g of silica-coated magnetic nanoparticles in PBS buffer solution, add 0.1mol of crosslinking agent EDC and 0.1mol of NHS, stir for 1h to obtain activated magnetic nanoparticles; then add 2g of endotoxin affinity peptide, incubate at room temperature for 30min, then add 0.1wt% BSA for blocking for 20min, and finally perform magnetic separation washing with PBS buffer solution to obtain magnetic composite adsorbent.

[0061] Example 3

[0062] This embodiment provides a magnetic composite adsorbent for hemoperfusion, the preparation method of which includes:

[0063] 1. Disperse 100g of magnetic nanoparticles (purchased from Hangzhou Jikang New Materials Co., Ltd., 200-300nm) in a pure ethanol solution, ultrasonically disperse, wash, and then resuspend in 200mL of 60-80vol% ethanol solution.

[0064] 2. Dissolve 18g of tetramethylsilane in hydrochloric acid solution to obtain a 0.1mol / L tetramethylsilane solution. Add this solution to the ethanol dispersion of magnetic nanoparticles obtained in step (1), and then add 4mL of ammonia water. React at 50-60℃ for 2-3h, and then wash with ethanol, water and PBS buffer solution (pH 7.4) in sequence to obtain magnetic nanoparticles coated with silica; 3. Resuspend 60g of silica-coated magnetic nanoparticles in PBS buffer solution, add 0.3mol of crosslinking agent EDC and 0.3mol of NHS, stir for 1h to obtain activated magnetic nanoparticles; then add 2g of endotoxin affinity peptide, incubate at room temperature for 60min, then add 0.1wt% BSA for blocking for 20min, and finally perform magnetic separation washing with PBS buffer solution to obtain magnetic composite adsorbent.

[0065] Example 4

[0066] This embodiment provides a magnetic composite adsorbent for hemoperfusion, the preparation method of which differs from that of Example 1 in that: an equimolar amount of chondroitin sulfate-modified toxin affinity peptide (provided in Preparation Example 1) is added in step (3).

[0067] Example 5

[0068] This embodiment provides a magnetic composite adsorbent for hemoperfusion, the preparation method of which differs from that of Example 1 in that: an equimolar amount of chondroitin sulfate-modified toxin affinity peptide (provided in Preparation Example 2) is added in step (3).

[0069] Example 6

[0070] This embodiment provides a magnetic composite adsorbent for hemoperfusion, the preparation method of which differs from that of Example 1 in that: an equimolar amount of chondroitin sulfate-modified toxin affinity peptide (provided in Preparation Example 3) is added in step (3).

[0071] Example 7

[0072] This embodiment provides a magnetic composite adsorbent for hemoperfusion, the preparation method of which differs from that of Example 1 in that: an equimolar amount of chondroitin sulfate-modified toxin affinity peptide (provided in Preparation Example 4) is added in step (3).

[0073] Example 8

[0074] This embodiment provides a magnetic composite adsorbent for hemoperfusion, the preparation method of which differs from that of Example 1 in that: an equimolar amount of chondroitin sulfate-modified toxin affinity peptide (provided in Preparation Example 5) is added in step (3).

[0075] Comparative Examples 1-3

[0076] This comparative example provides a magnetic composite adsorbent, the preparation method of which differs from that of Example 1 in that the polypeptide sequence immobilized on the magnetic nanoparticles is different, specifically:

[0077] Table 1.

[0078] polypeptide sequence serial number Example 1 Lys-His-Arg-Asp-Cys-Lys-Trp-Leu-Lys-Arg-Cys-Trp SEQ ID.01 Comparative Example 1 Lys-His-Arg-Asp-Cys-Lys-Trp-Leu-Lys-Arg-Try-Trp SEQ ID.02 Comparative Example 2 Lys-His-Arg-Asp-Try-Ala-Trp-Leu-Lys-Arg-Cys-Trp SEQ ID.03 Comparative Example 3 Lys-His-Arg-Asp-Cys-Ala-Trp-Leu-Ala-Arg-Cys-Trp SEQ ID.04

[0079] Comparative Example 4

[0080] This comparative example provides a magnetic composite adsorbent, the preparation method of which differs from that of Example 1 in that: in step (3), an equimolar amount of hyaluronic acid-modified toxin affinity peptide (provided in Preparation Example 6) is added.

[0081] Performance testing

[0082] Detection methods / test methods

[0083] I. Endotoxin Adsorption Test

[0084] The adsorbent materials provided in Examples 1 and 4, as well as Comparative Examples 1-4, were wet-packed into columns (φ1×10cm), pre-purged with physiological saline, and then 30mL of bovine plasma with added endotoxin (wherein the concentration of endotoxin was 8EU / mL) was added. The adsorption cycle was performed for 3h, and the endotoxin content in the bovine plasma before and after adsorption was tested. The clearance rate (R) was calculated according to the following formula: R=(C0-C1) / C0*100%.

[0085] In the formula, C0 and C1 represent the concentrations of endotoxins in the plasma before and after adsorption (EU / mL), respectively.

[0086] The results are shown in Table 2:

[0087] Table 2.

[0088] Adsorbent Clearance rate (%) Example 1 91.25 Example 4 90.47 Comparative Example 1 63.26 Comparative Example 2 56.18 Comparative Example 3 66.73 Comparative Example 4 82.04

[0089] As can be seen from Table 2:

[0090] As can be seen from Example 1 and Comparative Examples 1-3, the magnetic composite adsorbent provided in Example 1 of this application achieves an endotoxin removal rate of up to 91.25%, far exceeding that of Comparative Examples 1-3. This demonstrates that the polypeptide sequence shown in SEQ ID.01 provided in this application has a specific adsorption effect on endotoxins. Changing the cysteine ​​and arginine in the sequence reduces the surface positive charge of the polypeptide sequence and is not conducive to the formation of an entangled structure that can specifically bind endotoxins.

[0091] As can be seen from Examples 1, 4 and Comparative Example 4, when chondroitin sulfate is used to modify endotoxins with a specific sequence, the endotoxin clearance rate can still be maintained at over 90%; while when modified with hyaluronic acid, the endotoxin clearance rate is significantly reduced to 82%. This shows that the choice of modifying material for endotoxin peptides with a specific sequence can significantly affect their adsorption performance for endotoxins.

[0092] II. Blood compatibility test

[0093] Hemolysis tests were conducted according to GB / T16886.4-2003 Biological Evaluation of Medical Devices Part 4: Selection of Blood Interaction Tests and GB / T16175-2008 Biological Evaluation Test Methods for Medical Organosilicon Materials.

[0094] Calculate the hemolysis rate using the following formula:

[0095] 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.

[0096] The results are shown in Table 3:

[0097] Table 3.

[0098] Adsorbent Hemolysis rate (%) Example 1 4.18 Example 4 2.07 Comparative Example 1 5.26 Comparative Example 2 6.84 Comparative Example 3 6.27 Comparative Example 4 4.73

[0099] As can be seen from Table 3:

[0100] The hemolysis rates of the magnetic composite adsorbents obtained in Examples 1 and 4 of this application are both lower than the 5% requirement of the national standard, indicating that the magnetic composite adsorbents provided in this application have good blood compatibility. Furthermore, compared to Example 4, the endotoxin affinity peptide in Example 4, after modification with chondroitin sulfate, exhibits an even lower hemolysis rate, indicating better blood compatibility and safety. In Comparative Example 4, the endotoxin affinity peptide, after modification with hyaluronic acid, although the hemolysis rate is less than the 5% requirement of the national standard, shows a slight increase compared to Example 1, suggesting that the hyaluronic acid-modified magnetic composite adsorbent may trigger some hemolytic reactions. The hemolysis rates of the magnetic composite adsorbents provided in Comparative Examples 1-3 all fail to meet the national standard.

[0101] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A magnetic composite adsorbent for hemoperfusion, characterized by, The magnetic composite adsorbent takes magnetic nanoparticles as the core, is connected with endotoxin affinity peptide through a cross-linking agent, and forms a composite adsorbent. The amino acid sequence of the endotoxin affinity peptide is: Lys-His-Arg-Asp-Cys-Lys-Trp-Leu-Lys-Arg-Cys-Trp.

2. The magnetic composite adsorbent for hemoperfusion according to claim 1, characterized by, The magnetic nanoparticles are Fe3O4 particles, and the particle size of the magnetic nanoparticles is 100-300 nm.

3. The magnetic composite adsorbent for hemoperfusion according to claim 1, wherein The endotoxin affinity peptide is a modified endotoxin affinity peptide modified by chondroitin sulfate.

4. The magnetic composite adsorbent for hemoperfusion according to claim 3, characterized by, The preparation method of the modified endotoxin affinity peptide comprises: The endotoxin affinity peptide is dissolved in ethanol to obtain an endotoxin affinity peptide solution; Chondroitin sulfate and dicyclohexyl carbodiimide are added to the endotoxin affinity peptide solution, and a condensation reaction is carried out at 30-40°C to obtain chondroitin sulfate-modified endotoxin affinity peptide.

5. The magnetic composite adsorbent for hemoperfusion according to claim 4, characterized by, The molar ratio of the endotoxin affinity peptide to the chondroitin sulfate is 1:1.3-1.

5.

6. The magnetic composite adsorbent for hemoperfusion according to claim 4, wherein The condensation reaction time is 2-4 h.

7. A process for the preparation of the magnetic composite adsorbent according to any one of claims 1 to 6, characterized in that, It comprises: The magnetic nanoparticles are placed in an ethanol solution of 60-80 vol%, ultrasonically dispersed, then a hydrochloric acid solution of tetramethylsilane is added, an inorganic lye is added, and a reaction is carried out at 50-60°C for 2-3 h, then the magnetic nanoparticles coated with silica are obtained by washing with a PBS buffer solution; The magnetic nanoparticles coated with silica are resuspended in a PBS buffer solution, a cross-linking agent EDC and NHS are added and stirred for 1-2 h, then the endotoxin affinity peptide is added, and incubation is carried out at room temperature for 30-60 min to obtain the magnetic composite adsorbent.

8. The method of claim 7, wherein the magnetic composite adsorbent is prepared by a process comprising: The mass ratio of the magnetic nanoparticles coated with silica to the endotoxin affinity peptide is 20-30:

1.

9. The method of claim 7, wherein the magnetic composite adsorbent is prepared by a process comprising: The endotoxin affinity peptide is a modified endotoxin affinity peptide modified by chondroitin sulfate, and the preparation method of the modified endotoxin affinity peptide comprises: The endotoxin affinity peptide is dissolved in ethanol to obtain an endotoxin affinity peptide solution; Chondroitin sulfate and dicyclohexyl carbodiimide are added to the endotoxin affinity peptide solution, and a condensation reaction is carried out at 30-40°C to obtain chondroitin sulfate-modified endotoxin affinity peptide.

10. Use of the magnetic composite adsorbent according to any one of claims 1-6 in the preparation of a hemoperfusion device.