Bilirubin adsorption material as well as preparation method and application thereof

Abstract

The invention provides a bilirubin adsorbing material as well as a preparation method and application thereof, and belongs to the technical field of blood perfusion materials. The bilirubin adsorption material is mainly prepared from chitosan quaternary ammonium salt, microfibrillated cellulose, a surfactant and a cross-linking agent, wherein the surfactant is one or more of lauryl methacrylate, Span 80 and Span 85. The structure of the bilirubin adsorption material is that a hydrophilic polysaccharide chain is stabilized in a pore wall shell, and a hydrophobic chain of a surfactant is repelled and assembled to a pore wall core. When the bilirubin adsorption material adsorbs albumin-bilirubin, the adsorption effect is better than that of MFC / QCS frozen gel, and the adsorption capacity and the adsorption rate are enhanced along with the increase of the concentration of albumin.

Description

Technical Field

[0001] This invention relates to the field of blood perfusion materials technology, and in particular to a bilirubin adsorption material, its preparation method and application. Background Technology

[0002] Hyperbilirubinemia is a pathological state in which the serum total bilirubin concentration exceeds the physiological threshold due to dysfunction of bilirubin metabolism or excretion pathways. Its core mechanism involves the abnormal accumulation of bilirubin in the patient's blood. Hyperbilirubinemia can induce kernicterus, acute liver failure, multiple organ dysfunction, and even death. Timely removal of excess bilirubin is the gold standard for treating hyperbilirubinemia. Although traditional treatments (phototherapy, medication, plasma exchange) are effective in specific situations, their application has significant limitations. Phototherapy is mainly suitable for newborns; medications (such as phenobarbital) have a slow onset of action and limited efficacy in severe hyperbilirubinemia; plasma exchange carries a high risk of infection and consumes plasma resources. In particular, these traditional methods often fail to meet the need for rapid and safe bilirubin removal in severe or refractory hyperbilirubinemia (such as acute liver failure, the transition period of biliary obstruction, and hereditary bilirubin metabolism disorders), necessitating the development of more efficient and universal bilirubin removal strategies.

[0003] In recent years, hemoperfusion (HP) has gradually attracted attention as an in vitro support technology for directly targeting and removing toxic substances from the blood. Bilirubin hemoperfusion, through the strong affinity of adsorbent materials for bilirubin, can efficiently and rapidly remove bilirubin, demonstrating unique advantages in the treatment of severe hyperbilirubinemia. Currently, commonly used adsorbent media in clinical practice mainly include activated carbon and ion-exchange resins. However, due to the weak binding capacity of activated carbon and resins to bilirubin, their adsorption capacity for bilirubin is relatively low. Simultaneously, their hydrophobic surfaces easily adsorb plasma proteins, leading to poor blood compatibility. Natural polymers, due to their better blood compatibility, have received widespread attention in the field of hemoperfusion. Considering the low bilirubin removal capacity of natural polymers, a series of biohybrid materials have been developed by combining various high specific surface area inorganic materials with natural polymers. For example, combining carbon nanotubes, graphene oxide, and MXene into chitosan has improved the bilirubin removal capacity to some extent. However, the addition of excessive inorganic materials can lead to decreased blood compatibility and the shedding of inorganic materials. Furthermore, a series of hemoperfusion materials have been constructed by combining collagen, lysozyme, and natural polysaccharides, but their bilirubin clearance efficiency and specific adsorption still need improvement. In summary, existing hemoperfusion materials all face a triangular balance problem of "high bilirubin clearance efficiency - specific adsorption - good biocompatibility," which limits the widespread clinical application of hemoperfusion. Bilirubin is a tetrapyrrole lipid-soluble molecule produced by the degradation of heme. In blood, it binds to albumin to maintain its water solubility. Albumin has a high affinity for bilirubin (approximately 1 × 10⁻⁶). 7 M -1 This limitation restricts the clearance of bilirubin by hemoperfusion materials. For example, when the albumin concentration increased from 0 to 50 mg / mL, the adsorption capacity of collagen-functionalized chitosan microspheres for bilirubin decreased from 260.6 mg / g to 67.1 mg / g. Other reported adsorption materials all showed a significant decrease in bilirubin adsorption at high albumin concentrations. Overcoming the limitation of high albumin-bilirubin binding rates on bilirubin clearance remains unreported and presents a significant challenge. Summary of the Invention

[0004] The purpose of this invention is to provide a bilirubin adsorbent material, its preparation method, and its application, so as to solve the problem of bilirubin adsorption limitation in existing adsorbent materials due to the competitive adsorption of bilirubin by albumin.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] This invention provides a bilirubin adsorbent material, which is mainly prepared from chitosan quaternary ammonium salt (QCS), microfibrillated cellulose (MFC), surfactant and crosslinking agent;

[0007] The surfactant is one or more of lauryl methacrylate, Span 80, and Span 85.

[0008] Preferably, the mass ratio of the chitosan quaternary ammonium salt, microfibrillated cellulose, and crosslinking agent is 0.3–1.0: 0.1–0.3: 0.2–0.4; and the mass-volume ratio of the chitosan quaternary ammonium salt and surfactant is 0.3–1.0 g: 200–300 μL.

[0009] This invention provides a method for preparing the bilirubin adsorbent material described above, comprising the following steps:

[0010] (1) Mix microfibrillated cellulose, chitosan quaternary ammonium salt and water to obtain a mixed solution;

[0011] (2) Add surfactant and crosslinking agent to the mixed solution and freeze to obtain bilirubin adsorbent material.

[0012] Preferably, in step (1), the mixing time is 1 to 3 hours.

[0013] Preferably, in step (2), a surfactant is first added to the mixed solution and stirred for 10 to 20 minutes.

[0014] Preferably, in step (2), after adding the crosslinking agent, the mixture is stirred vigorously for 3 to 7 minutes.

[0015] Preferably, in step (2), the freezing temperature is -15 to -10°C and the freezing time is 10 to 14 hours.

[0016] Preferably, in step (2), thawing at room temperature is required after freezing.

[0017] Preferably, in step (2), the product is washed after thawing at room temperature.

[0018] The present invention also provides the application of the bilirubin adsorbent material described above or the bilirubin adsorbent material prepared by the above-described method in the preparation of blood perfusion materials.

[0019] The beneficial effects of this invention are:

[0020] The raw materials used in this invention to prepare bilirubin adsorbent materials are inexpensive, widely available, environmentally friendly, and have good biocompatibility. The preparation method is simple and meets the requirements of sustainable development.

[0021] The structure of the bilirubin adsorbent material of the present invention is that hydrophilic polysaccharide chains are stabilized on the outer shell of the pore wall, and the hydrophobic chains of the surfactant are repelled and assembled into the core of the pore wall.

[0022] The bilirubin adsorbent material of the present invention exhibits better adsorption performance than MFC / QCS cryogel when adsorbing albumin-bilirubin, and the adsorption amount and adsorption rate increase with increasing albumin concentration.

[0023] The bilirubin adsorbent material of this invention improves the clinical efficacy and safety of hemoperfusion. Adsorption data and anticoagulation tests show that the bilirubin adsorbent material does not cause hemolysis, coagulation, complement activation, has low cytotoxicity, and exhibits good biocompatibility. Attached Figure Description

[0024] Figure 1 The images show the contact angles of the MFC / QCS / LMA in Example 1 and the MFC / QCS in Comparative Example 4, as well as the pore size distribution of the MFC / QCS / LMA in Example 1, where a is the contact angle and b is the pore size distribution.

[0025] Figure 2 The charts show a comparison of the adsorption capacity and removal rate of albumin-bilirubin by MFC / QCS / LMA in Example 1, MFC / QCS / PA in Comparative Example 1, MFC / QCS / SDS in Comparative Example 2, MFC / QCS / LA in Comparative Example 3, MFC / QCS / Span 80 in Example 4, and MFC / QCS / Span 85 in Example 5. In the chart, a is the adsorption capacity comparison chart and b is the removal rate comparison chart.

[0026] Figure 3 The graphs show a comparison of the adsorption capacity and removal rate of bilirubin by MFC / QCS / LMA in Example 1 and MFC / QCS in Comparative Example 4 at different BSA concentrations.

[0027] Figure 4 The results of hemolysis experiments for the positive control group, negative control group, MFC / QCS / LMA of Example 1, and MFC / QCS of Comparative Example 4 are shown. The APTT, TT, PT, and FIB values ​​of the control group, MFC / QCS / LMA of Example 1, and MFC / QCS of Comparative Example 4 are also shown. SEM images of MFC / QCS / LMA of Example 1, as well as SEM images of adhesion to erythrocytes and platelets, are also shown. In the figures, a represents the hemolysis experiment results, b represents the APTT, TT, and PT values, c represents the FIB value, d represents the SEM image of MFC / QCS / LMA of Example 1, e represents the SEM image of MFC / QCS / LMA of Example 1 adhering to erythrocytes, and f represents the SEM image of MFC / QCS / LMA of Example 1 adhering to platelets. Detailed Implementation

[0028] This invention provides a bilirubin adsorbent material, which is mainly prepared from chitosan quaternary ammonium salt, microfibrillated cellulose, surfactant and crosslinking agent;

[0029] The surfactant is one or more of lauryl methacrylate, Span 80, and Span 85.

[0030] In this invention, the crosslinking agent is preferably bisvinylsulfonylmethane (BVSM).

[0031] In this invention, the mass ratio of chitosan quaternary ammonium salt, microfibrillated cellulose, and crosslinking agent is 0.3–1.0:0.1–0.3:0.2–0.4, preferably 0.4–0.9:0.2:0.3, and more preferably 0.6–0.8:0.2:0.3; the mass-volume ratio of chitosan quaternary ammonium salt and surfactant is 0.3–1.0 g:200–300 μL, preferably 0.4–0.9 g:220–280 μL, and more preferably 0.6–0.8:250 μL.

[0032] This invention provides a method for preparing the bilirubin adsorbent material described above, comprising the following steps:

[0033] (1) Mix microfibrillated cellulose, chitosan quaternary ammonium salt and water to obtain a mixed solution;

[0034] (2) Add surfactant and crosslinking agent to the mixed solution and freeze to obtain bilirubin adsorbent material.

[0035] In the invention, the specific steps of mixing microfibrillated cellulose, chitosan quaternary ammonium salt and water in step (1) are as follows: mixing microfibrillated cellulose and water to obtain a suspension of microfibrillated cellulose, and then adding chitosan quaternary ammonium salt. The mass concentration of the microfibrillated cellulose suspension is 0.5-1.5%, preferably 1.0%.

[0036] In this invention, in step (1), the mixing time is 1 to 3 hours, preferably 1.5 to 2.5 hours, and more preferably 2 hours.

[0037] In this invention, in step (2), a surfactant is first added to the mixed solution and stirred for 10 to 20 minutes, preferably 12 to 18 minutes, and more preferably 15 minutes.

[0038] In this invention, in step (2), after adding the crosslinking agent, the mixture is stirred vigorously. The stirring speed is 500-700 rpm, preferably 600 rpm, and the stirring time is 3-7 min, preferably 4-6 min, and more preferably 5 min.

[0039] In this invention, in step (2), the freezing temperature is -15 to -10°C, preferably -14 to -11°C, more preferably -13 to -12°C, and the freezing time is 10 to 14 hours, preferably 11 to 13 hours, more preferably 12 hours.

[0040] In this invention, after freezing, step (2) requires thawing at room temperature.

[0041] In this invention, in step (2), the product is washed after thawing at room temperature.

[0042] In this invention, the washing process is as follows: after thawing at room temperature, the product is washed sequentially with deionized water, hydrochloric acid solution, sodium hydroxide solution, and physiological saline.

[0043] The bilirubin adsorbent material of this invention is a microporous heterostructure material with a hydrophilic surface and strong binding sites for bilirubin inside. The micropores allow only small bilirubin molecules to enter while blocking large albumin molecules, thus enhancing bilirubin selectivity through a dual mechanism of confined adsorption and chemical affinity.

[0044] Chitosan quaternary ammonium salt, a hydrophilic natural polymer, constructs strong binding sites for bilirubin through the self-assembly of surfactants and chitosan quaternary ammonium salt. To form confined adsorption micropores, micropores of approximately 5 nm were constructed by extruding polysaccharides with ice crystals during freezing. Simultaneously, microfibrillated cellulose (MFC) was used to enhance the mechanical properties of the material. Furthermore, divinyl sulfone methane (BVSM) was used as a crosslinking agent for freeze-induced chemical crosslinking of chitosan quaternary ammonium salt, constructing cryogels with ultra-large porous flow channels and microporous confined adsorption. During freezing, ice crystal growth causes hydrophilic polysaccharide chains to form the outer shell of the pore wall, while hydrophobic surfactant chains assemble into the core of the pore wall, forming a "hydrophilic-hydrophobic" heterostructure that encapsulates the bilirubin binding sites within the pore wall. After albumin transports bilirubin to the hydrophilic pore wall shell, bilirubin is adsorbed into the hydrophobic pore wall, while albumin cannot enter due to the confinement effect, thus overcoming the competitive limitation of albumin on bilirubin adsorption. The adsorbent material prepared in this invention adsorbs bilirubin, and the results show that the adsorption capacity and clearance rate of bilirubin increase with increasing albumin concentration, which is different from the results reported in all current literature.

[0045] The present invention also provides the application of the bilirubin adsorbent material described above or the bilirubin adsorbent material prepared by the above-described method in the preparation of blood perfusion materials.

[0046] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0047] Example 1

[0048] 0.2 g of microfibrillated cellulose was mixed with water to obtain a 1.0% (w / w) MFC suspension. Then, 0.6 g of chitosan quaternary ammonium salt was added, and the mixture was mechanically stirred to ensure uniform mixing. After 2 h, 250 μL of lauryl methacrylate was added, and the mixture was stirred for 15 min. Subsequently, 0.3 g of divinylsulfonylmethane was added, and the mixture was stirred vigorously for 5 min. The resulting mixture was transferred to a plastic syringe and frozen at -12 °C for 12 h to obtain an MFC / QCS / LMA cryogel. The MFC / QCS / LMA cryogel was thawed at room temperature and thoroughly washed with deionized water, hydrochloric acid solution (1 mol / L), sodium hydroxide solution (1 mol / L), and physiological saline, respectively. Ethanol exchange was performed, and finally, the gel was air-dried at 50 °C to obtain the bilirubin adsorbent material, denoted as MFC / QCS / LMA.

[0049] Example 2

[0050] 0.3 g of microfibrillated cellulose was mixed with water to obtain a 1.5% (w / w) MFC suspension. Then, 1.0 g of chitosan quaternary ammonium salt was added, and the mixture was mechanically stirred to ensure uniform mixing. After 3 h, 200 μL of lauryl methacrylate was added, and the mixture was stirred for 20 min. Subsequently, 0.4 g of divinylsulfonylmethane was added, and the mixture was stirred vigorously for 7 min. The resulting mixture was transferred to a plastic syringe and frozen at -10 °C for 10 h to obtain an MFC / QCS / LMA cryogel. The MFC / QCS / LMA cryogel was thawed at room temperature and thoroughly washed with deionized water, hydrochloric acid solution (1 mol / L), sodium hydroxide solution (1 mol / L), and physiological saline, respectively. Ethanol exchange was performed, and finally, the gel was air-dried at 50 °C to obtain the bilirubin adsorbent material.

[0051] Example 3

[0052] 0.1 g of microfibrillated cellulose was mixed with water to obtain a 0.5% (w / w) MFC suspension. Then, 0.3 g of chitosan quaternary ammonium salt was added, and the mixture was mechanically stirred to ensure uniform mixing. After 1 h, 300 μL of lauryl methacrylate was added, and the mixture was stirred for 10 min. Subsequently, 0.2 g of divinylsulfonylmethane was added, and the mixture was stirred vigorously for 3 min. The resulting mixture was transferred to a plastic syringe and frozen at -15 °C for 14 h to obtain an MFC / QCS / LMA cryogel. The MFC / QCS / LMA cryogel was thawed at room temperature and thoroughly washed with deionized water, hydrochloric acid solution (1 mol / L), sodium hydroxide solution (1 mol / L), and physiological saline, respectively. Ethanol exchange was performed, and finally, the gel was air-dried at 50 °C to obtain the bilirubin adsorbent material.

[0053] Example 4

[0054] The difference from Example 1 is that the added surfactant is Span 80, and all other conditions are the same, resulting in a bilirubin adsorbent material, denoted as MFC / QCS / Span 80.

[0055] Example 5

[0056] The difference from Example 1 is that the surfactant added is Span 85, and all other conditions are the same, resulting in a bilirubin adsorbent material, denoted as MFC / QCS / Span 85.

[0057] Comparative Example 1

[0058] The difference from Example 1 is that the added surfactant is palmitic acid (PA), and all other conditions are the same, resulting in a bilirubin adsorbent material, denoted as MFC / QCS / PA.

[0059] Comparative Example 2

[0060] The difference from Example 1 is that the added surfactant is sodium dodecyl sulfate (SDS), while all other conditions are the same, resulting in a bilirubin adsorbent material, denoted as MFC / QCS / SDS.

[0061] Comparative Example 3

[0062] The difference from Example 1 is that the added surfactant is lauric acid (LA), and all other conditions are the same, resulting in a bilirubin adsorbent material, denoted as MFC / QCS / LA.

[0063] Comparative Example 4

[0064] 0.2 g of microfibrillated cellulose was mixed with water to obtain a 0.1% MFC suspension. Then, 0.6 g of chitosan quaternary ammonium salt was added, and the mixture was mechanically stirred to ensure uniform mixing. The resulting mixture was transferred to a plastic syringe and frozen at -12°C for 12 h to obtain an MFC / QCS cryogel. The MFC / QCS cryogel was thawed at room temperature and thoroughly washed with deionized water, hydrochloric acid solution (1 mol / L), sodium hydroxide solution (1 mol / L), and physiological saline, respectively. Ethanol exchange was performed, and finally, the gel was air-dried at 50°C to obtain the bilirubin adsorbent material, denoted as MFC / QCS.

[0065] The wettability of MFC / QCS / LMA and MFC / QCS was quantitatively analyzed using a contact angle goniometer. For example... Figure 1 As shown in Figure a, the water contact angle (WCA) of MFC / QCS / LMA was found to be 0°, the same as that of MFC / QCS, highlighting their respective hydrophilic properties. Furthermore, a wetting time of 2 seconds was observed for MFC / QCS / LMA, indicating rapid absorption of water droplets when placed on its surface. This superior adsorption performance of MFC / QCS / LMA can be attributed to the hydrophilic polysaccharide chains located on the pore wall shell, which are repelled and assembled into the hydrophobic surfactant core. This unique property achieves an optimal hydrophilic-hydrophobic balance, enhancing liquid permeability and facilitating the efficient removal of bilirubin. The pore size distribution curve shows (…). Figure 1 b) The pore volume increases significantly in the pore size range of 3-7 nm, and there are stratified pores; the average pore size of MFC / QCS / LMA cryogel is 5.9 nm, while the diameter of bilirubin molecules (1.0-1.5 nm) is much smaller than the average pore size of the adsorbent material (5.9 nm), allowing them to freely enter micropores and mesopores. At the same time, the hydrophobicity of bilirubin enables it to specifically bind to hydrophobic groups (such as LMA) in the adsorbent material to enhance the adsorption efficiency.

[0066] Different surfactants showed significantly different adsorption effects on albumin-bilirubin (e.g., Figure 2(As shown in a and b). The MFC / QCS / LMA cryogel exhibited the best adsorption capacity (100.3 mg / g, 76.2% clearance rate) and the worst performance (MFC / QCS / PA cryogel, only 47.9 mg / g, 35.6% clearance rate). This difference stems from the degree of cross-linking between the surfactant and BVSM: the vinyl groups of BVSM readily react with compounds containing electron-rich double bonds or nucleophilic groups under sulfonyl activation. LMA, due to its high double bond reactivity, showed significantly better cross-linking efficiency than the sterically hindered Span 85 and Span 80. Lauric acid (LA) required strong alkali and high temperature for weak cross-linking, while palmitic acid (PA) showed almost no reaction. Sodium dodecyl sulfate (SDS), lacking reactive functional groups, did not participate in cross-linking at all. Weakly cross-linked surfactants are easily eluted, leading to a decrease in adsorption performance; therefore, MFC / QCS / LMA showed the best adsorption effect.

[0067] Given the complex composition of blood, adsorption selectivity is crucial for evaluating the performance of bilirubin adsorbents. This invention investigates the adsorption selectivity of MFC / QCS / LMA cryogels using an albumin-bilirubin solution in a simulated plasma environment. Experiments revealed ( Figure 3 (a) and (b) show that the bilirubin adsorption capacity and clearance rate of the MFC / QCS / LMA cryogel generally increased with albumin concentration from 10 g / L to 40 g / L, and decreased slightly at 50 g / L; while the adsorption capacity and clearance rate of the MFC / QCS cryogel decreased with increasing albumin concentration. Since bilirubin is an albumin-bound toxin in blood with an albumin concentration of 35–50 g / L, an albumin concentration of 40 g / L was chosen for the experiment. The results showed that the removal efficiency and adsorption capacity of the MFC / QCS / LMA cryogel for bilirubin reached 77.3% and 101.1 mg / g, respectively, significantly higher than the 34.0% and 43.7 mg / g of the MFC / QCS cryogel. The two materials exhibited opposite adsorption effects, presumably because the MFC / QCS / LMA cryogel, due to the hydrophobicity of LMA, can competitively adsorb albumin-bound bilirubin in addition to adsorbing free bilirubin.

[0068] To assess the biocompatibility of MFC / QCS / LMA, hemolysis, coagulation, and blood adhesion tests were performed. Rupture of red blood cell membranes leads to the release of hemoglobin into the surrounding fluid and the formation of a thrombus. According to ASTM F756-2008, materials with a hemolysis rate of <5% are considered safe for blood perfusion. Figure 4As shown in Figure a, the positive control group experienced severe erythrocyte damage, resulting in hemoglobin release and a noticeably red color. Conversely, in the negative control group, erythrocytes aggregated at the bottom after centrifugation, with no hemoglobin release and no observed red color. After incubation with MFC / QCS / LMA, the blood supernatant remained clear, indicating no erythrocyte rupture or hemoglobin release. The hemolysis rate of MFC / QCS / LMA was 2.64%, and that of MFC / QCS was 2.26%, both significantly lower than the ASTM standard of 5%. These results indicate that both materials cause minimal erythrocyte damage and do not induce an acute hemolytic reaction.

[0069] In coagulation tests, clotting time, including activated partial thromboplastin time (APTT) and prothrombin time (PT), is measured. Figure 4 As shown in b, the TT value of MFC / QCS / LMA decreased slightly to 9.7s compared to the control group, but remained within the normal range. The APTT and PT values ​​showed no significant difference compared to the control group, indicating that the MFC / QCS / LMA cryogel has a certain anticoagulant effect in the intrinsic coagulation system and does not contain significant procoagulant components. Figure 4 As shown in Figure c, the FIB level was lower in the MFC / QCS / LMA cryogel compared to the MFC / QCS cryogel, but overall, the FIB levels of both cryogels were higher than the control group. These results suggest that the MFC / QCS / LMA cryogel may exhibit a mild adsorption effect on FIB without impairing normal coagulation function. When a large number of platelets adhere to the material surface, the coagulation system may be activated, potentially leading to clot formation and blockage. Figure 4 Images e and 4f clearly show the partial adhesion of erythrocytes and platelets to the material surface after incubation with whole blood and PRP. Notably, platelets on the MFC / QCS / LMA cryogel maintained their structural integrity without forming pseudopodia. Furthermore, erythrocyte adhesion to the surface was minimal, with no signs of rupture, indicating that the MFC / QCS / LMA cryogel exhibits excellent blood compatibility.

[0070] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A bilirubin adsorbing material, characterized by, The bilirubin adsorption material is prepared from chitosan quaternary ammonium salt, microfibrillated cellulose, a surfactant and a crosslinking agent. The surfactant is one or more of lauryl methacrylate, Span 80 and Span 85.

2. The bilirubin adsorbent material of claim 1, wherein The mass ratio of the chitosan quaternary ammonium salt, the microfibrillated cellulose and the crosslinking agent is 0.3-1.0:0.1-0.3:0.2-0.4; and the mass-volume ratio of the chitosan quaternary ammonium salt and the surfactant is 0.3-1.0 g:200-300 μL.

3. The method of producing a bilirubin adsorbing material according to claim 1 or 2, characterized by, The method comprises the following steps: (1) mixing the microfibrillated cellulose, the chitosan quaternary ammonium salt and water to obtain a mixed solution; (2) adding the surfactant and the crosslinking agent to the mixed solution and freezing to obtain the bilirubin adsorption material.

4. The method for preparing the bilirubin adsorbent material according to claim 3, characterized in that, In step (1), the mixing time is 1-3 h.

5. The method for producing a bilirubin adsorbing material according to claim 3 or 4, characterized by, In step (2), the surfactant is first added to the mixed solution and stirred for 10-20 min.

6. The method of claim 5, wherein the adsorbent material is prepared by the steps of: In step (2), the crosslinking agent is added and then stirred vigorously for 3-7 min.

7. The method for producing a bilirubin adsorbing material according to claim 4 or 6, characterized by, In step (2), the freezing temperature is-15 to-10 ℃ and the freezing time is 10-14 h.

8. The method of claim 7, wherein the adsorbent material is prepared by the steps of: In step (2), after freezing, the material is thawed at room temperature.

9. The method for preparing the bilirubin adsorbent material according to claim 8, characterized in that, In step (2), after thawing at room temperature, the material is washed.

10. Use of the bilirubin adsorption material of claim 1 or 2 or the bilirubin adsorption material prepared by the method of any one of claims 3-9 in preparing a blood perfusion material.

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