Magnetic composite adsorbent for blood perfusion as well as preparation method and application of magnetic composite adsorbent

Abstract

The invention relates to the field of medical instruments, and particularly discloses a magnetic composite adsorbent for blood perfusion as well as a preparation method and application of the magnetic composite adsorbent. According to the magnetic composite adsorbent, magnetic nanoparticles serve as an inner core and are connected with endotoxin affinity peptide through a cross-linking agent, and the composite adsorbent is formed; the amino acid sequence of the endotoxin affinity peptide is as follows: Lys-His-Arg-Asp-Cys-Lys-Trp-Leu-Lys-Arg-Cys-Trp, and the amino acid sequence of the endotoxin affinity peptide is as follows: Lys-His-Arg-Asp- The magnetic composite adsorbent has specific affinity to endotoxin, and the endotoxin affinity peptide is fixed on the surface of the magnetic nanoparticle through a chemical bond, so that the adsorbent is easy to recover through magnetic separation in the blood perfusion process, and the endotoxin affinity peptide is not easy to fall off and remain in blood; therefore, the method is safer and more efficient.

Description

Technical Field

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

[0002] Hemoperfusion (HP) is a blood purification technology that introduces the patient's blood into a perfusion device filled with solid adsorbents to remove exogenous or endogenous toxins, drugs or metabolic wastes in the blood that cannot be removed by dialysis through adsorption. It is mainly used to rescue drug and poison poisoning, and can also be used in combination with hemodialysis to remove large molecular toxins in patients with chronic renal failure who are undergoing maintenance dialysis. The basic principle of hemoperfusion is adsorption. The perfusion column is composed of an adsorbent and a wrapping material. The adsorbent has the ability to adsorb dissolved substances and colloidal substances in the liquid.

[0003] Polymyxin B is an antibiotic that has an inhibitory effect on a variety of negative bacteria, and is particularly sensitive to other antibiotic-resistant strains. In the prior art, polymyxin B is often adsorbed and fixed to the amino group of α-chloroacetamide-methyl polystyrene fiber to form a polymyxin B fixed fiber blood perfusion device. Polymyxin B has a high affinity for the lipid A part of lipopolysaccharide, so it can adsorb and remove endotoxins in the blood. However, in this method, polymyxin B is fixed to the fiber by adsorption, and may fall off during the perfusion process and remain in the blood; and because polymyxin B has poor stability and strong nephrotoxicity and neurotoxicity, there are great safety risks in practical applications. Summary of the invention

[0004] In order to improve the adsorption efficiency of endotoxin by the adsorbent during blood perfusion and reduce toxicity and potential risks, the present application provides a magnetic composite adsorbent for blood perfusion and a preparation method and application thereof.

[0005] This application adopts the following technical solutions: In a first aspect, a magnetic composite adsorbent for blood perfusion, wherein the magnetic composite adsorbent has magnetic nanoparticles as the core and is connected to an endotoxin affinity peptide via a cross-linking agent to form 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.

[0006] The magnetic composite adsorbent provided by the above technical solution uses magnetic nanoparticles as the core carrier, which is connected to the endotoxin affinity peptide of a specific sequence through a chemical bond to form a composite adsorbent with high affinity, high specificity and high detoxification activity for the target endotoxin. This endotoxin affinity peptide is screened by phage surface display technology based on Escherichia coli endotoxin as a model, and has a specific affinity for endotoxin. This may be because the basic amino acids in the peptide chain of the endotoxin affinity peptide can form ionic interactions with the phosphate group of the endotoxin, and the disulfide bond formed between the two cysteines in the peptide chain makes the endotoxin affinity peptide form a special entangled structure, thereby showing a strong specific adsorption ability for endotoxin. In the process of synthesizing the above magnetic composite adsorbent, the endotoxin affinity peptide of the above sequence is artificially synthesized and then fixed on the magnetic nano ions.

[0007] Compared with the blood perfusion adsorbent in the prior art that uses polymyxin B as the adsorbent, this magnetic composite adsorbent has a comparable ability to purify endotoxins in the blood, but does not produce nephrotoxicity and neurotoxicity; and because the endotoxin affinity peptide is fixed to the surface of the magnetic nanoparticles by chemical bonds, the adsorbent can be easily recovered by magnetic separation during the blood perfusion process, and the endotoxin affinity peptide is not easy to fall off and remain in the blood, making it safer and more efficient.

[0008] Furthermore, the magnetic nanoparticles are Fe3O4 particles, and the particle size of the magnetic nanoparticles is 100-300nm.

[0009] The magnetic nanoparticles of this size have the characteristics of large specific surface area, strong magnetic responsiveness, good biocompatibility and easy adsorption, and are easy to perform magnetic separation during blood perfusion. Preferably, the particle size of the magnetic nanoparticles is 200-300 nm.

[0010] Furthermore, the above-mentioned endotoxin affinity peptide is a modified endotoxin affinity peptide modified by chondroitin sulfate.

[0011] Furthermore, the preparation method of the modified endotoxin affinity peptide comprises: dissolving the endotoxin affinity peptide in ethanol to obtain an endotoxin affinity peptide solution; Chondroitin sulfate and dicyclohexylcarbodiimide are added to the endotoxin affinity peptide solution, and a condensation reaction is carried out at 30-40° C. to obtain a chondroitin sulfate-modified endotoxin affinity peptide.

[0012] In the preferred technical solution of the present application, the endotoxin affinity peptide of the above-mentioned specific sequence is chemically modified with chondroitin sulfate to improve the stability and biocompatibility of the endotoxin affinity peptide, thereby further improving the annual safety and prolonging the circulation time of the magnetic composite adsorbent during blood perfusion.

[0013] 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 endotoxin-affinity peptide of the above-mentioned specific sequence to form an amide bond or an ester bond, thereby connecting chondroitin sulfate to the endotoxin-affinity peptide. Experiments have shown that the affinity of the endotoxin-affinity peptide modified with chondroitin sulfate for endotoxin has not decreased, which shows that chondroitin sulfate has no effect on the active center of the endotoxin-affinity peptide.

[0014] Furthermore, 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.

[0015] Furthermore, the condensation reaction time is 2-4 hours, preferably, the condensation reaction time is 2.5-3.5 hours.

[0016] In a second aspect, the present application provides a method for preparing the above-mentioned magnetic composite adsorbent, which comprises: The magnetic nanoparticles are placed in a 60-80 vol% ethanol solution, and after ultrasonic dispersion, a tetramethylsilane hydrochloric acid solution is added, and an inorganic alkali solution is added to react at 50-60° C. for 2-3 hours, and then washed with a PBS buffer solution to obtain magnetic nanoparticles coated with silica; The magnetic nanoparticles coated with silica are resuspended in a PBS buffer solution, crosslinking agents EDC and NHS are added and stirred for 1-2 hours, and then the endotoxin affinity peptide is added and incubated at room temperature for 30-60 minutes to obtain the magnetic composite adsorbent.

[0017] Furthermore, the mass ratio of the magnetic nanoparticles coated with silica to the endotoxin affinity peptide is 20-30:1.

[0018] Furthermore, the above-mentioned endotoxin affinity peptide is a modified endotoxin affinity peptide modified by chondroitin sulfate, and the preparation method of the modified endotoxin affinity peptide comprises: dissolving the endotoxin affinity peptide in ethanol to obtain an endotoxin affinity peptide solution; Chondroitin sulfate and dicyclohexylcarbodiimide are added to the endotoxin affinity peptide solution, and a condensation reaction is carried out at 30-40° C. to obtain a chondroitin sulfate-modified endotoxin affinity peptide.

[0019] In a third aspect, the present application provides a use of the above-mentioned magnetic composite adsorbent in the preparation of a blood perfusion device.

[0020] In summary, this application has the following beneficial effects: The magnetic composite adsorbent provided by the present application uses magnetic nanoparticles as core carriers, which are connected to endotoxin affinity peptides of specific sequences through chemical bonds to form a composite adsorbent with high affinity, high specificity and high detoxification activity for target endotoxins. This endotoxin affinity peptide is obtained by screening with Escherichia coli endotoxin as a model through phage surface display technology, and has a specific affinity for endotoxins. And because the endotoxin affinity peptide is fixed to the surface of the magnetic nanoparticles through chemical bonds, it is easy to recover the adsorbent through magnetic separation during blood perfusion, and the endotoxin affinity peptide is not easy to fall off and remain in the blood, so it is safer and more efficient. DETAILED DESCRIPTION

[0021] 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.

[0022] 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.

[0023] The endotoxin affinity peptide in the present application is obtained by screening through phage display technology and artificially synthesized after sequencing. The endotoxin affinity peptide is 12 amino acids in length, and the specific amino acid sequence is: Lys-His-Arg-Asp-Cys-Lys-Trp-Leu-Lys-Arg-Cys-Trp (SEQ ID.01).

[0024] Preparation examples of raw materials and / or intermediates Preparation Example 1 This preparation example provides a modified endotoxin affinity peptide, and its preparation method includes: 1. A specific endotoxin affinity peptide was synthesized by solid phase synthesis, the sequence of which is shown in SEQ ID.01. This step was completed by a biological company.

[0025] 2. Dissolve 200 g of endotoxin affinity peptide with a purity of more than 99% in 100 mL of ethanol to obtain an endotoxin affinity peptide solution with a concentration of 2 mg / mL; 3. Disperse chondroitin sulfate in 20 ml of water for dissolution, add it to the endotoxin affinity peptide solution after dissolution, and then add the condensation 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.

[0026] 4. The mixed reaction solution was placed in a water bath at 35°C for 3 hours, and then washed with ethanol and PBS buffer solution in sequence to obtain a chondroitin sulfate-modified toxin affinity peptide.

[0027] Preparation Example 2 This preparation example provides a modified endotoxin affinity peptide, and its preparation method is different 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.

[0028] Preparation Example 3 This preparation example provides a modified endotoxin affinity peptide, and its preparation method is different 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.

[0029] Preparation Example 4 This preparation example provides a modified endotoxin affinity peptide, and its preparation method is different from that of Preparation Example 1 in that: in the last step, the mixed reaction solution is placed in a water bath at 30° C. for reaction for 4 hours.

[0030] Preparation Example 5 This preparation example provides a modified endotoxin affinity peptide, and its preparation method is different from that of Preparation Example 1 in that: in the last step, the mixed reaction solution is placed in a water bath at 40° C. for reaction for 2 hours.

[0031] Preparation Example 6 This preparation example provides a modified endotoxin affinity peptide, and its preparation method is different from that of Preparation Example 1 in that chondroitin sulfate is replaced by an equal molar amount of hyaluronic acid. Example

[0032] Example 1 This embodiment provides a magnetic composite adsorbent for blood perfusion, and the preparation method thereof includes: 1. Disperse 100 g of magnetic nanoparticles (purchased from Hangzhou Jikang New Materials Co., Ltd., 200-300 nm) into a pure ethanol solution, wash after ultrasonic dispersion, and then resuspend in 200 mL of 70 vol% ethanol solution.

[0033] 2. Dissolve 18 g of tetramethylsilane in hydrochloric acid solution to obtain a 0.1 mol / L tetramethylsilane solution. Add the solution to the ethanol dispersion of magnetic nanoparticles obtained in step (1), then drop 4 mL of ammonia water, react at 55°C for 3 h, and then wash with ethanol, water and PBS buffer solution (pH 7.4) in sequence to obtain magnetic nanoparticles coated with silica; 3. Resuspend the silica-coated magnetic nanoparticles (50 g) in PBS buffer solution, add 0.2 mol EDC and 0.2 mol NHS as cross-linking agents, stir for 1 hour to obtain activated magnetic nanoparticles; then add 2 g of endotoxin affinity peptide, incubate at room temperature for 45 minutes, then add 0.1 wt% BSA for blocking for 20 minutes, and finally perform magnetic separation and washing with PBS buffer solution to obtain a magnetic composite adsorbent.

[0034] Example 2 This embodiment provides a magnetic composite adsorbent for blood perfusion, and the preparation method thereof includes: 1. Disperse 100 g of magnetic nanoparticles (purchased from Hangzhou Jikang New Materials Co., Ltd., 200-300 nm) into a pure ethanol solution, wash after ultrasonic dispersion, and then resuspend in 200 mL of 60-80 vol% ethanol solution.

[0035] 2. Dissolve 18g of tetramethylsilane in hydrochloric acid solution to obtain a 0.1mol / L tetramethylsilane solution. Add the solution to the ethanol dispersion of magnetic nanoparticles obtained in step (1), then drop 2mL of ammonia water, react at 50-60°C for 2-3h, and wash with ethanol, water and PBS buffer solution (pH 7.4) in turn to obtain magnetic nanoparticles coated with silicon dioxide; 3. Resuspend the magnetic nanoparticles coated with silicon dioxide (40g) in PBS buffer solution, add 0.1mol of EDC and 0.1mol of NHS as crosslinking agents, stir for 1h, and obtain activated magnetic nanoparticles; then add 2g of endotoxin affinity peptide, incubate at room temperature for 30min, then add 0.1wt% of BSA for blocking for 20min, and finally perform magnetic separation and washing with PBS buffer solution to obtain a magnetic composite adsorbent.

[0036] Example 3 This embodiment provides a magnetic composite adsorbent for blood perfusion, and the preparation method thereof includes: 1. Disperse 100 g of magnetic nanoparticles (purchased from Hangzhou Jikang New Materials Co., Ltd., 200-300 nm) into a pure ethanol solution, wash after ultrasonic dispersion, and then resuspend in 200 mL of 60-80 vol% ethanol solution.

[0037] 2. Dissolve 18g of tetramethylsilane in hydrochloric acid solution to obtain a 0.1mol / L tetramethylsilane solution. Add the solution to the ethanol dispersion of magnetic nanoparticles obtained in step (1), then drop 4mL of ammonia water, react at 50-60°C for 2-3h, and wash with ethanol, water and PBS buffer solution (pH 7.4) in sequence to obtain magnetic nanoparticles coated with silicon dioxide; 3. Resuspend the magnetic nanoparticles coated with silicon dioxide (60g) in PBS buffer solution, add 0.3mol of EDC and 0.3mol of NHS as crosslinking agents, stir for 1h, and obtain activated magnetic nanoparticles; then add 2g of endotoxin affinity peptide, incubate at room temperature for 60min, then add 0.1wt% of BSA for blocking for 20min, and finally perform magnetic separation and washing with PBS buffer solution to obtain a magnetic composite adsorbent.

[0038] Example 4 This example provides a magnetic composite adsorbent for blood perfusion. The preparation method thereof is different 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).

[0039] Example 5 This example provides a magnetic composite adsorbent for blood perfusion. The preparation method thereof is different 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).

[0040] Example 6 This example provides a magnetic composite adsorbent for blood perfusion. The preparation method thereof is different 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).

[0041] Example 7 This example provides a magnetic composite adsorbent for blood perfusion. The preparation method thereof is different 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).

[0042] Example 8 This example provides a magnetic composite adsorbent for blood perfusion. The preparation method thereof is different 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).

[0043] Comparative Examples 1-3 This group of comparative examples provides a magnetic composite adsorbent, and its preparation method is different from that of Example 1 in that the polypeptide sequence fixed on the magnetic nanoparticles is different, specifically: Table 1. Peptide 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 Comparative Example 4 This comparative example provides a magnetic composite adsorbent, and its preparation method is different from that of Example 1 in that an equimolar amount of hyaluronic acid-modified toxin affinity peptide (provided in Preparation Example 6) is added in step (3).

[0044] Performance testing Detection method / test method 1. Endotoxin adsorption test The adsorption materials provided in Examples 1 and 4 and Comparative Examples 1-4 were wet packed into a column (φ1×10 cm), pre-flushed with physiological saline, and then 30 mL of bovine plasma to which endotoxin had been added (wherein the concentration of endotoxin was 8 EU / mL) was added. The dynamic adsorption cycle was 3 h, 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%; Where C0 and C1 represent the concentration of endotoxin in plasma before and after adsorption (EU / mL), respectively.

[0045] The results are shown in Table 2: Table 2. 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 It can be seen from Table 2 that: As can be seen from Example 1 and Comparative Examples 1-3, the removal rate of endotoxin by the magnetic composite adsorbent provided in Example 1 of the present application is as high as 91.25%, far exceeding Comparative Examples 1-3. This shows that the polypeptide sequence shown in SEQ ID.01 provided in the present application has a specific adsorption effect on endotoxin. When the cysteine ​​and arginine in the sequence are changed, the surface positive charge of the polypeptide sequence will be reduced, and it is not conducive to the formation of an entangled structure that can specifically bind to endotoxin.

[0046] It can be seen from Example 1, Example 4 and Comparative Example 4 that when chondroitin sulfate is used to modify the endotoxin of a specific sequence, the clearance rate of endotoxin can still be maintained at more than 90%; and after modification with hyaluronic acid, the clearance rate of endotoxin is significantly reduced to 82%. It can be seen that the selection of the modification material for the endotoxin polypeptide of a specific sequence will significantly affect its adsorption performance for endotoxin.

[0047] 2. Blood compatibility test The hemolysis experiment was carried out according to "GB / T16886.4-2003 Biological Evaluation of Medical Devices Part 4 Selection of Tests for Interaction with Blood" and "GB / T16175-2008 Test Methods for Biological Evaluation of Medical Silicone Materials".

[0048] 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.

[0049] The results are shown in Table 3: Table 3. 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 It can be seen from Table 3 that: The hemolysis rates of the magnetic composite adsorbents obtained in Examples 1 and 4 of the present application are lower than the 5% required by the national standard, indicating that the magnetic composite adsorbent provided by the present application has good blood compatibility. At the same time, compared with Example 4, the hemolysis rate of the endotoxin affinity peptide in Example 4 is lower after being modified with chondroitin sulfate in Example 1, indicating that it has better blood compatibility and safety. In Comparative Example 4, after the endotoxin affinity peptide is modified with hyaluronic acid, although the hemolysis rate is less than 5% required by the national standard, it is slightly higher than that in Example 1, which indicates that the magnetic composite adsorbent modified with hyaluronic acid may induce some hemolytic reactions. The hemolysis rates of the magnetic composite adsorbents provided in Comparative Examples 1-3 do not meet the national standards.

[0050] 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 magnetic composite adsorbent for blood perfusion, characterized in that: The magnetic composite adsorbent has magnetic nanoparticles as the core, which are connected to the endotoxin affinity peptide via a cross-linking agent to form 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 blood perfusion according to claim 1, characterized in that: The magnetic nanoparticles are Fe3O4 particles, and the particle size of the magnetic nanoparticles is 100-300nm.

3. The magnetic composite adsorbent for blood perfusion according to claim 1, characterized in that: The endotoxin affinity peptide is a modified endotoxin affinity peptide modified by chondroitin sulfate.

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

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

5.

6. The magnetic composite adsorbent for blood perfusion according to claim 4, characterized in that: The condensation reaction time is 2-4h.

7. A method for preparing a magnetic composite adsorbent according to any one of claims 1 to 6, characterized in that: It includes: The magnetic nanoparticles are placed in a 60-80 vol% ethanol solution, and after ultrasonic dispersion, a tetramethylsilane hydrochloric acid solution is added, and an inorganic alkali solution is added to react at 50-60° C. for 2-3 hours, and then washed with a PBS buffer solution to obtain magnetic nanoparticles coated with silica; The magnetic nanoparticles coated with silica are resuspended in a PBS buffer solution, crosslinking agents EDC and NHS are added and stirred for 1-2 hours, and then the endotoxin affinity peptide is added and incubated at room temperature for 30-60 minutes to obtain the magnetic composite adsorbent.

8. The method for preparing the magnetic composite adsorbent according to claim 7, characterized in that: The mass ratio of the magnetic nanoparticles coated with silica to the endotoxin affinity peptide is 20-30:

1.

9. The method for preparing a magnetic composite adsorbent according to claim 7, characterized in that: 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: dissolving the endotoxin affinity peptide in ethanol to obtain an endotoxin affinity peptide solution; Chondroitin sulfate and dicyclohexylcarbodiimide are added to the endotoxin affinity peptide solution, and a condensation reaction is carried out at 30-40° C. to obtain a chondroitin sulfate-modified endotoxin affinity peptide.

10. Use of the magnetic composite adsorbent according to any one of claims 1 to 6 in preparing a blood perfusion device.