Multifunctional adsorbent and preparation method and application thereof

Abstract

The application provides a multifunctional adsorbent and a preparation method and application thereof, and the multifunctional adsorbent comprises a carrier and a functional layer arranged on the outer layer of the carrier; the carrier is polystyrene-epoxy resin; the functional layer is composed of a first grafting layer and a second grafting layer, the first grafting layer is formed by reacting tryptophan with the epoxy group of the carrier, and the second grafting layer is formed by reacting polyacrylic acid with the acryloyl group introduced on the carrier. The multifunctional adsorbent can simultaneously adsorb FIB, LDL-C and key inflammatory factors in blood, so as to reduce the high coagulation state of blood, improve lipid metabolism and inhibit excessive inflammatory reaction, thereby providing an effective scheme which can significantly improve the clinical prognosis for CLTI patients who cannot accept blood revascularization.

Description

Technical Field

[0001] This invention relates to the field of in vitro blood purification technology, and more specifically, to a multifunctional adsorbent, its preparation method, and its application. Background Technology

[0002] Peripheral artery disease (PAD) has become a global public health burden, affecting more than 200 million patients. Approximately 10% of these patients progress to chronic limb-threatening ischemia (CLTI). CLTI patients not only face an extremely high risk of cardiovascular events, with a 5-year all-cause mortality rate as high as 40%, but also experience severe rest pain, refractory ulcers, and gangrene, resulting in a very poor quality of life. For these patients, timely and effective revascularization (including endovascular intervention or surgical bypass grafting) is the cornerstone of limb salvage and improved prognosis.

[0003] Although revascularization is the preferred option in most cases, clinical practice shows that over 20% of CLTI patients are excluded from treatment options due to the lack of open endovascular surgery or physical weakness. These patients currently only receive palliative wound care (relieving local symptoms through basic wound cleaning and dressing changes) or amputation (a last resort when limb ischemia is severe and no other effective treatments are available). Palliative wound care cannot fundamentally improve the limb's ischemic state and the systemic hypercoagulable and hyperinflammatory state; it only provides temporary symptom control and has little effect on promoting ulcer healing, reducing amputation rates, or prolonging survival. While amputation can prevent life-threatening complications such as severe infection, it directly leads to permanent disability, accompanied by postoperative difficulties adapting to prostheses, loss of mobility, and psychological trauma, severely reducing the patient's quality of life. Both of these options have significant limitations and cannot meet the core needs of patients to prolong life and preserve limbs.

[0004] Given the obvious limitations of existing therapies, there is an urgent clinical need for a new and improved treatment approach to fill the treatment gap for patients who are "unreplaceable" and meet their core needs of limb preservation and life extension. Summary of the Invention

[0005] This invention aims to provide a multifunctional adsorbent, its preparation method, and its application. This multifunctional adsorbent can simultaneously adsorb fibrinogen (FIB), low-density lipoprotein cholesterol (LDL-C), and key inflammatory factors in the blood circulation, thereby reducing the hypercoagulable state of the blood, improving lipid metabolism, and inhibiting excessive inflammatory response. From a pathophysiological perspective, it improves the microcirculation and inflammatory state of the lower extremity veins in patients, promotes ulcer healing, and thus provides an effective solution that can significantly improve the clinical prognosis of CLTI patients who cannot undergo revascularization.

[0006] To address the above problems, a first aspect of the present invention provides a multifunctional adsorbent, comprising a carrier and a functional layer disposed on the outer layer of the carrier;

[0007] The carrier is polystyrene-epoxy resin;

[0008] The functional layer consists of a first grafted layer and a second grafted layer. The first grafted layer is formed by reacting tryptophan with the epoxy groups of the carrier, and the second grafted layer is formed by reacting polyacrylic acid with acryloyl groups introduced on the carrier.

[0009] Furthermore, the first grafted layer is formed by covalently linking the tryptophan with the epoxy group of the support via a nucleophilic addition reaction, and the second grafted layer is formed by the polyacrylic acid with the acryloyl group introduced on the support via an addition polymerization reaction, wherein the acryloyl group is introduced after acrylating the support.

[0010] Furthermore, the grafting rate of tryptophan on the multifunctional adsorbent is 50 wt% to 100 wt%, and the grafting rate of polyacrylic acid is 50 wt% to 100 wt%.

[0011] Furthermore, the carrier has a particle size between 0.3 mm and 0.8 mm, an average pore size between 7 nm and 20 nm, and a pore volume of 0.8 cm³. 3 / g to 1.5cm 3 / g, specific surface area is 300m² 2 / g to 600m 2 / g, with an epoxy content ranging from 0.03 mmol / ml to 0.1 mmol / ml.

[0012] A second aspect of the present invention provides a method for preparing a multifunctional adsorbent, which is used to prepare the multifunctional adsorbent as described in the first aspect, comprising the following steps:

[0013] Polystyrene-epoxy resin is provided as a carrier;

[0014] The epoxy groups on the support are reacted with tryptophan to form a first grafting layer on the surface of the support, thereby obtaining a first grafted support.

[0015] Acrylyl groups were introduced onto the first grafting support to prepare a second grafting support.

[0016] The acryloyl groups on the second grafted carrier are reacted with polyacrylic acid to form a second grafted layer on the surface of the carrier, thereby obtaining the multifunctional adsorbent.

[0017] Further, the step of reacting the epoxy groups on the support with tryptophan to form a first graft layer on the surface of the support, thereby obtaining the first grafted support, includes:

[0018] The tryptophan was prepared into a tryptophan solution;

[0019] The carrier and the tryptophan solution are mixed at a volume ratio of 1:(1-10) and reacted with shaking at 20°C to 50°C for 2 to 10 hours to connect the tryptophan with epoxy groups, thereby forming the first grafted layer on the surface of the carrier and obtaining the first grafted carrier.

[0020] Further, the tryptophan is prepared into a tryptophan solution, comprising:

[0021] The tryptophan was dissolved in a sodium hydroxide solution, and then a carbonate buffer solution with a pH of 9 to 12 was added to prepare a tryptophan solution. The concentration of the carbonate buffer solution was 0.05 mol / L to 2 mol / L.

[0022] Further, the step of introducing acryloyl groups onto the first grafting support to obtain the second grafting support includes:

[0023] Anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride were added to the first grafting carrier. After stirring and reacting at 20°C to 50°C for 3 to 8 hours, water for injection was added to terminate the reaction. Acryloyl groups were introduced onto the first grafting carrier to obtain the second grafting carrier.

[0024] The mass ratio of the first grafting carrier, anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride is 1:(10-40):(2-5):(2-5).

[0025] Further, the step of reacting the acryloyl groups on the second grafted support with polyacrylic acid to form a second grafted layer on the surface of the support to obtain the multifunctional adsorbent includes:

[0026] The second grafted carrier is added to DMF for swelling treatment, then ammonium persulfate is added, and the temperature is raised to 30°C to 80°C. Under a protective atmosphere of continuous nitrogen gas, polyacrylic acid is slowly added dropwise and stirred for 3 to 20 hours to allow the polyacrylic acid to react with acryloyl groups and form a second grafted layer on the surface of the carrier, thus obtaining the multifunctional adsorbent.

[0027] The mass ratio of the second grafting carrier, DMF, ammonium persulfate and polyacrylic acid is 1:(1-5):(0.1-1):(2-20).

[0028] A third aspect of the present invention provides a perfusion device comprising a multifunctional adsorbent as described in the first aspect, or comprising a multifunctional adsorbent prepared by the preparation method described in the second aspect, wherein the perfusion device is used for the adsorption of FIB, LDL-C and inflammatory factors during extracorporeal blood circulation.

[0029] The multifunctional adsorbent provided by this invention uses polystyrene-epoxy resin as a carrier. Polystyrene-epoxy resin possesses good blood compatibility and high mechanical strength, and its own three-dimensional porous network structure allows it to adsorb inflammatory factors through molecular sieving, van der Waals forces, and lipophilic-hydrophobic interactions. The tryptophan grafted onto the outer layer of the carrier has an indole ring. This indole ring, through hydrophobic interactions and π-π stacking, can specifically adsorb inflammatory factors (such as IL-1β) containing aromatic rings or hydrophobic regions. The multifunctional adsorbent, grafted onto the outer layer of a carrier containing LDL-6 and fibrinogen, contains a large number of carboxyl groups. These negatively charged carboxyl groups can bind to positively charged LDL-C through electrostatic interactions. The polyacrylic acid also exhibits appropriate carboxyl group density, good grafting controllability, and good biocompatibility. Furthermore, the tryptophan layer, possessing both biocompatibility and amphiphilicity, can synergistically optimize interfacial properties with the polyacrylic acid layer. Tryptophan, a natural amino acid, contains a hydrophobic indole ring, hydrophilic amino / carboxyl groups, and a reactive amino group (α-amino). Grafting it onto the polystyrene-epoxy resin surface enhances the biocompatibility of this multifunctional adsorbent by modifying its hydrophobicity to hydrophilicity, eliminating epoxy irritation, introducing bioactive sites, and inhibiting nonspecific adsorption. This invention provides a multifunctional adsorbent that, through the cooperation between the carrier and the functional layer, can simultaneously adsorb LDL-C, inflammatory factors, and FIB via three different adsorption mechanisms, effectively reducing LDL-C, inflammatory factors, and FIB in the blood. Polystyrene-epoxy resin is chemically bonded to both tryptophan and polyacrylic acid, which ensures a strong bond between tryptophan and polystyrene-epoxy resin, as well as between polyacrylic acid and polystyrene-epoxy resin. This reduces the risk of tryptophan and polyacrylic acid detachment and helps ensure the safety of the multifunctional adsorbent.

[0030] The method for preparing the multifunctional adsorbent provided by this invention uses polystyrene-epoxy resin as a carrier. The surface of polystyrene-epoxy resin has a large number of epoxy active groups. Tryptophan can be grafted onto the carrier through a nucleophilic addition reaction, so that the epoxy active groups and tryptophan are connected by chemical bonds. After tryptophan is grafted onto the carrier, the epoxy groups on the surface of the carrier form hydroxyl groups through ring opening. After the newly formed hydroxyl groups undergo an acrylylation reaction, acryloyl groups can be introduced onto the carrier. Then, polyacrylic acid is grafted onto the carrier through an addition polymerization reaction, so that polyacrylic acid and acryloyl groups are connected by chemical bonds. The preparation method of this invention involves grafting tryptophan and polyacrylic acid onto the outer layer of a carrier. With the synergy of the carrier, tryptophan, and polyacrylic acid, simultaneous adsorption of LDL-C, inflammatory factors, and FIB can be achieved, effectively reducing LDL-C, inflammatory factors, and FIB in the blood. Furthermore, the polystyrene-epoxy resin is chemically bonded to both tryptophan and polyacrylic acid, ensuring a strong bond between them. This reduces the risk of tryptophan and polyacrylic acid detachment, thus ensuring the safety of the multifunctional adsorbent. In addition, the preparation method provided by this invention involves relatively few reaction steps, a relatively simple preparation process, mild reaction conditions, high safety during the reaction process, and low production costs, making it suitable for industrial production. Attached Figure Description

[0031] Figure 1 This is a process flow diagram for preparing a multifunctional adsorbent according to an embodiment of the present invention. Detailed Implementation

[0032] In related technologies, fibrinogen (FIB), a large plasma protein, can significantly increase blood viscosity when its concentration rises. Studies have shown that when fibrinogen concentration exceeds 4 g / L, plasma viscosity can increase by approximately 40%, and whole blood viscosity by 25%, leading to a decrease in blood flow velocity, especially at the microvascular level, such as a 15%–20% reduction in capillary blood flow. Furthermore, FIB can promote thrombus formation; fibrinogen can activate platelet aggregation, accelerate fibrin network formation, and increase the risk of arterial thrombosis. Prospective cohort studies have shown that patients with chronic limb-threatened ischemia (CLTI) (415.5 mg / dL) had significantly higher fibrinogen levels than patients only exhibiting intermittent claudication (293.00 mg / dL).

[0033] In a hyperglycemic environment, advanced glycation end products (AGEs) can bind to the receptor RAGE, activating the nuclear transcription factor NF-κB signaling pathway, upregulating the expression of pro-inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while inhibiting the production of anti-inflammatory mediators such as interleukin-10 (IL-10), thus forming a vicious cycle of "inflammation-oxidative stress-tissue damage." This process can inhibit epithelial cell migration and proliferation, as well as angiogenesis, prolonging the inflammatory phase of the wound. The "Guidelines for the Diagnosis and Treatment of Diabetic Foot in China (2024 Edition)" points out that aspirin can reduce the release of prostaglandins and other inflammatory mediators by inhibiting cyclooxygenase activity, thereby alleviating the inflammatory response, improving local blood circulation, and promoting wound healing. Numerous clinical studies have confirmed that reducing serum inflammatory factor levels (such as IL-6, TNF-α, and C-reactive protein CRP) can accelerate the healing of diabetic foot wounds, significantly shorten the time required for granulation tissue formation and epithelialization, and reduce ulcer area, thus having a positive impact on improving patients' clinical prognosis. Diabetic foot is closely related to peripheral artery disease (PAD), and the presence of PAD is a significant risk factor for poor healing and amputation. In clinical practice, early screening and revascularization of PAD must be emphasized to improve patients' quality of life and limb salvage rates.

[0034] Elevated low-density lipoprotein cholesterol (LDL-C) levels are a core driver of atherosclerosis, directly leading to lipid deposition in the blood vessel walls and luminal narrowing, increasing blood flow resistance. According to the global vascular management guidelines for CLTI (Chronic Artery Injury Therapy) patients, when LDL-C > 4.14 mmol / L, the risk of atherosclerosis increases approximately threefold, and LDL-C levels are positively correlated with the degree of lower extremity arterial stenosis (for every 1 mmol / L increase in LDL-C, the ankle-brachial index (ABI) decreases by approximately 0.05). For CLTI patients, the guidelines recommend controlling LDL-C to < 1.8 mmol / L or reducing it by ≥ 50% from baseline to slow disease progression and reduce the risk of restenosis after revascularization (achieving this target can reduce restenosis rate by approximately 28%).

[0035] As described above, simultaneously reducing the levels of LDL-C, inflammatory factors, and fibrinogen in the blood can significantly improve patients' blood circulation, promote ulcer healing, and reduce amputation and mortality rates. However, there is a lack of drugs or dedicated adsorbents capable of simultaneously and efficiently adsorbing LDL-C, inflammatory factors, and fibrinogen in the blood. While some blood purification methods can achieve these goals, such as plasma filtration devices using a combination of three membranes with different pore sizes and materials, which can adsorb LDL-C, inflammatory factors, and fibrinogen in plasma to a certain extent, their separation principle mainly relies on the sieving effect of molecular size, lacking selectivity and specificity. In practical applications, such devices may non-specifically remove a large amount of beneficial plasma components while removing the target harmful substances, thus affecting treatment efficacy and patient safety.

[0036] In order to address the aforementioned problems in related technologies, this application provides a multifunctional adsorbent, its preparation method, and its application. This multifunctional adsorbent can simultaneously adsorb fibrinogen (FIB), low-density lipoprotein cholesterol (LDL-C), and key inflammatory factors in the patient's blood circulation, thereby reducing hypercoagulability, improving lipid metabolism, and inhibiting excessive inflammatory response. From a pathophysiological perspective, it improves the microcirculation and inflammatory state of the patient's lower extremities, promotes ulcer healing, and thus provides an effective solution that can significantly improve the clinical prognosis of CLTI patients who cannot undergo revascularization.

[0037] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0038] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other.

[0039] Furthermore, the terms "comprising," "including," "containing," and "having" are non-restrictive and can refer to the addition of other steps and components that do not affect the results. Unless otherwise specified, all materials, equipment, and reagents are commercially available.

[0040] Furthermore, although the present invention describes each step in the preparation process in the form of S110, S120 and S130, this description is only for ease of understanding. The forms such as S110, S120 and S130 do not indicate a limitation on the order of the steps.

[0041] A first aspect of this application provides a multifunctional adsorbent, which includes a carrier and a functional layer disposed on the outer layer of the carrier;

[0042] The carrier is polystyrene-epoxy resin; the functional layer consists of a first grafted layer and a second grafted layer. The first grafted layer is formed by the reaction of tryptophan with the epoxy groups of the carrier, and the second grafted layer is formed by the reaction of polyacrylic acid with acryloyl groups introduced on the carrier.

[0043] The multifunctional adsorbent provided in this embodiment uses polystyrene-epoxy resin as a carrier. Polystyrene-epoxy resin has good blood compatibility and high mechanical strength, and it itself has a three-dimensional porous network structure, which can adsorb inflammatory factors through molecular sieving, van der Waals forces, and lipophilic-hydrophobic interactions. The tryptophan grafted onto the outer layer of the carrier has an indole ring. The indole ring, through hydrophobic interactions and π-π stacking, can specifically adsorb inflammatory factors (such as IL-1β) containing aromatic rings or hydrophobic regions. The multifunctional adsorbent grafted onto the outer layer of the carrier contains a large number of carboxyl groups, which are negatively charged and can bind to positively charged LDL-C through electrostatic interactions. The polyacrylic acid also exhibits appropriate carboxyl group density, good grafting controllability, and good biocompatibility. Furthermore, the tryptophan layer is biocompatible and amphiphilic, synergistically optimizing interfacial properties with the polyacrylic acid layer. Tryptophan, a natural amino acid, contains a hydrophobic indole ring, hydrophilic amino / carboxyl groups, and a reactive amino group (α-amino). Grafting it onto the polystyrene-epoxy resin surface enhances the biocompatibility of this multifunctional adsorbent by modifying hydrophobicity to hydrophilicity, eliminating epoxy irritation, introducing bioactive sites, and inhibiting nonspecific adsorption. In this embodiment, the multifunctional adsorbent, through the cooperation between the carrier and the functional layer, can simultaneously adsorb LDL-C, inflammatory factors, and FIB via three different adsorption mechanisms, effectively reducing LDL-C, inflammatory factors, and FIB in the blood. Polystyrene-epoxy resin is chemically bonded to both tryptophan and polyacrylic acid, which ensures a strong bond between tryptophan and polystyrene-epoxy resin, as well as between polyacrylic acid and polystyrene-epoxy resin. This reduces the risk of tryptophan and polyacrylic acid detachment and helps ensure the safety of the multifunctional adsorbent.

[0044] Based on the above embodiments, as an optional implementation, the first graft layer is formed by covalently linking tryptophan with the epoxy groups of the support via a nucleophilic addition reaction, and the second graft layer is formed by the addition polymerization of polyacrylic acid with acryloyl groups introduced on the support. The acryloyl groups are introduced after acrylating the support. The surface of polystyrene-epoxy resin has a large number of epoxy active groups, which can be chemically linked to tryptophan, making tryptophan firmly attached to the support. By introducing acryloyl groups through acrylating the support, the acryloyl groups can firmly attach the polyacrylic acid to the support.

[0045] In this application, for ease of description and understanding, the portion formed by connecting tryptophan to the carrier is defined as the first graft layer, and the portion formed by connecting polyacrylic acid to the carrier is defined as the second graft layer. In fact, both the first graft layer and the second graft layer are located on the outer layer of the carrier. They are not two clearly defined layers, nor is there a distinction between inner and outer layers.

[0046] Based on the above embodiments, as another optional implementation, the first grafting layer is formed by reacting tyrosine with the epoxy group of the support, or the first grafting layer is formed by reacting phenylalanine with the epoxy group of the support. Both tyrosine and phenylalanine exhibit hydrophobic interactions and π-π stacking, enabling them to specifically adsorb inflammatory factors such as IL-1β or IL-6 and fibrinogen. However, grafting tyrosine or phenylalanine reduces the adsorption efficiency and selectivity of this multifunctional adsorbent for inflammatory factors (such as IL-1β, IL-6) and fibrinogen. Therefore, preferably, the first grafting layer is formed by reacting tryptophan with the epoxy group of the support. Compared to tyrosine and phenylalanine, tryptophan has an indole ring in its side chain, which has stronger hydrophobicity and can improve the adsorption efficiency and selectivity for inflammatory factors (such as IL-1β, IL-6) and fibrinogen.

[0047] Based on the above embodiments, as a preferred embodiment, the molecular weight of polyacrylic acid is between 50 kDa and 80 kDa. The molecular weight of polyacrylic acid within this range ensures that the multifunctional adsorbent has an appropriate number of adsorption sites, good mass transfer resistance, and high grafting reaction efficiency.

[0048] Based on the above embodiments, as an optional implementation, the grafting rate of tryptophan on the multifunctional adsorbent is 50wt% to 100wt%, and the grafting rate of polyacrylic acid is 50wt% to 100wt%. Therefore, with the grafting rates of tryptophan and polyacrylic acid within the above ranges, the adsorption capacity of the multifunctional adsorbent for fibrinogen and LDL-C can be improved.

[0049] Based on the above embodiments, as an optional implementation, the particle size of the carrier is between 0.3 mm and 0.8 mm, the average pore size is between 7 nm and 20 nm, and the pore volume is 0.8 cm³. 3 / g to 1.5cm 3 / g, specific surface area (measured by BET method) ranges from 300m². 2 / g to 600m 2 / g, with an epoxy content of 0.03mmol / ml to 0.1mmol / ml (the amount of epoxy groups immobilized on each 1mL of carrier is 0.03mmol to 0.1mmol). Thus, the pore size, pore volume, and specific surface area of ​​the carrier are within the above range, giving the carrier a rich and appropriately sized pore structure. This allows the carrier to block large molecules such as high-density lipoprotein, globulin, and albumin, allowing only appropriately sized target substances to pass through, thereby achieving specific adsorption of inflammatory factors.

[0050] Figure 1 This is a process flow diagram for preparing multifunctional adsorbents provided in the embodiments of this application. (Combined with...) Figure 1 As shown, a second aspect of this application provides a method for preparing a multifunctional adsorbent, used to prepare the multifunctional adsorbent described in the first aspect. The method for preparing the multifunctional adsorbent includes the following steps:

[0051] Step S110: Provide polystyrene-epoxy resin as a carrier.

[0052] As an optional implementation, in this embodiment, polystyrene-epoxy resin can be prepared using the following method:

[0053] Divinylbenzene, styrene, and glycidyl methacrylate are subjected to suspension polymerization in a dispersion medium under the action of a porogen and an initiator. After the suspension polymerization is completed, polystyrene-epoxy resin is obtained. The temperature of the suspension polymerization reaction can be 70℃ to 90℃, and the time of the suspension polymerization reaction can be 4h to 12h.

[0054] Based on the above embodiments, as an optional implementation, the porogen is a mixture of two or more aromatic hydrocarbons, alkanes, higher alcohols, and higher ketones, and the porogen includes both good and poor solvents. Aromatic hydrocarbons and alkanes are good solvents; aromatic hydrocarbons include at least one of toluene, ethylbenzene, xylene, and n-propylbenzene; alkanes include at least one of n-heptane, liquid paraffin, and gasoline. Higher alcohols and higher ketones are poor solvents; higher alcohols include at least one of butanol, isooctanol, and methyl isobutyl methanol; higher ketones include at least one of methyl isobutyl ketone and 2-hexanone. The amount of poor solvent used is 30% to 200% of the mass of the good solvent, preferably 50% to 100% of the mass of the good solvent. In this embodiment, the amount of porogen used is 10% to 300% of the total mass of divinylbenzene, styrene, and glycidyl methacrylate.

[0055] Based on the above embodiments, as an optional implementation, the initiator is an organic peroxide or an alkylbenzene sulfone. The organic peroxide is one or a mixture of several of benzoyl peroxide, tert-butyl peroxide-2-hexylhexanoate, tert-amyl peroxide-2-ethylhexanoate, and dodecyl dibenzoyl peroxide; the alkylbenzene sulfone is one or a mixture of two of dihydroxyphenyl sulfone and tert-butylphenyl sulfone. If the initiator is a mixture of several substances, these substances can be mixed in any proportion. Preferably, the initiator is tert-butyl peroxide-2-hexylhexanoate. The amount of initiator used is 0.1% to 10% of the total mass of divinylbenzene, styrene, and glycidyl methacrylate.

[0056] Based on the above embodiments, as an optional implementation, the dispersion medium includes a dispersant and water. The dispersant is dissolved in the water to form the dispersion medium. The dispersant includes one or a mixture of gelatin, polyvinyl alcohol, and methylcellulose. The amount of dispersant used is 0.01% to 5% of the mass of the dispersion medium. If the dispersant is a mixture of several substances, these substances can be mixed in any proportion. In this embodiment, the volume ratio of the dispersion medium to the mixed organic phase is 1:2 to 5:1, wherein the mixed organic phase refers to a mixture composed of divinylbenzene, styrene, glycidyl methacrylate, a pore-forming agent, and an initiator.

[0057] The polystyrene-epoxy resin prepared by the method of this embodiment not only has a rich and appropriately sized pore structure, which enables the specific adsorption of inflammatory factors, but also has a large number of epoxy active groups on its surface, which can firmly connect tryptophan to the carrier.

[0058] Step S120: React the epoxy groups on the support with tryptophan to form a first grafted layer on the surface of the support, thereby obtaining the first grafted support.

[0059] Specifically, tryptophan is prepared into a tryptophan solution; the carrier is mixed with the tryptophan solution and reacted with shaking at 20°C to 50°C for 2 to 10 hours to allow the carrier and tryptophan to undergo a nucleophilic addition reaction, so that tryptophan is linked to epoxy groups, forming a first grafted layer on the surface of the carrier, thus obtaining the first grafted carrier.

[0060] More specifically, the carrier is washed 2 to 10 times with 20% to 75% ethanol, and then washed 5 to 10 times with water to obtain a cleaned carrier; tryptophan is prepared into a tryptophan solution; the cleaned carrier is added to the tryptophan solution, and then the reaction is carried out with shaking at 20°C to 50°C for 2 to 10 hours to graft tryptophan onto the surface of the carrier. After the reaction is completed, the reaction product is washed with water until neutral to obtain the first grafted carrier, that is, the tryptophan-grafted carrier.

[0061] Based on the above embodiments, as an optional implementation, the volume ratio of the carrier to the tryptophan solution is 1:(1-10), and the concentration of the tryptophan solution is 0.2 g / mL to 2 g / mL. Therefore, by controlling the volume ratio of the carrier to the tryptophan solution, the amount of tryptophan can be controlled. When tryptophan is grafted onto the carrier, some epoxy groups remain on the carrier surface. These epoxy groups will undergo ring-opening to form hydroxyl groups during the tryptophan grafting process, and the hydroxyl groups can further undergo subsequent acrylylation modification reactions.

[0062] Based on the above embodiments, as an optional implementation, tryptophan is prepared into a tryptophan solution by: dissolving tryptophan in a sodium hydroxide solution, and then adding a carbonate buffer solution with a pH of 9-12 to prepare a tryptophan solution, wherein the concentration of the carbonate buffer solution is 0.05 mol / L to 2 mol / L. Specifically, 10 g to 20 g of tryptophan is weighed and dissolved in 10 mL to 50 mL of a sodium hydroxide solution with a concentration of 0.1 mol / L to 2 mol / L, and then a carbonate buffer solution with a pH of 9-12 and a concentration of 0.05 mol / L to 2 mol / L is added to prepare a tryptophan solution.

[0063] When preparing the tryptophan solution, using an alkaline solution to dissolve tryptophan and adding a carbonate buffer solution with a pH of 9–12 pre-activates the functional group (indole ring) of tryptophan to a state with the strongest π-π stacking ability, creating an optimal charge and reaction environment for the effective and stable immobilization of tryptophan on the support. A wider concentration range of the carbonate buffer solution provides better controllability, allowing for a better balance between surface order and site density, thus optimizing the performance of the multifunctional adsorbent.

[0064] Step S130: Introduce acryloyl groups onto the first grafting support to obtain the second grafting support.

[0065] Specifically, anhydrous dichloromethane, acryloyl chloride, and anhydrous aluminum trichloride are added to the first grafting carrier. After stirring and reacting at 20°C to 50°C for 3 to 8 hours, water for injection is added to terminate the reaction, and acryloyl groups are introduced onto the first grafting carrier to obtain the second grafting carrier.

[0066] More specifically, anhydrous dichloromethane, acryloyl chloride, and anhydrous aluminum trichloride are added to the first grafting support. After stirring and reacting at 20°C to 50°C for 3 to 8 hours, water for injection is added to terminate the reaction, and acryloyl groups are introduced onto the first grafting support. After the reaction is completed, the reaction product is washed 2 to 8 times with anhydrous ethanol, distilled water, and methanol in sequence, and then dried under vacuum at 10°C to 40°C to constant weight to obtain the second grafting support, i.e., the acryloylated support.

[0067] Based on the above embodiments, as an optional implementation, the mass ratio of the first grafting support, anhydrous dichloromethane, acryloyl chloride, and anhydrous aluminum trichloride is 1:(10-40):(2-5):(2-5). Thus, anhydrous dichloromethane, as a solvent, within the above range, ensures sufficient swelling or dispersion of the first grafting support, promoting the diffusion of acryloyl chloride and anhydrous aluminum trichloride to the internal active sites of the first grafting support, thereby improving reaction uniformity. Acryloyl chloride, as an acylation reagent, within the above range, ensures sufficient acylation of available sites on the first grafting support to introduce sufficient acryloyl groups (double bonds) for subsequent grafting of polyacrylic acid. Anhydrous aluminum trichloride, as a Lewis acid catalyst, with its amount matched to that of acryloyl chloride, effectively forms an acyl cationic intermediate, promoting the rapid progress of the Friedel-Crafts acylation reaction and improving reaction efficiency.

[0068] Step S130: React the acryloyl groups on the second grafted support with polyacrylic acid to form a second grafted layer on the surface of the support, thereby preparing a multifunctional adsorbent.

[0069] Specifically, the second grafted carrier is added to DMF for swelling treatment, followed by the addition of ammonium persulfate and the temperature is raised to 30°C to 80°C. Under a protective atmosphere of continuous nitrogen purging, polyacrylic acid is slowly added dropwise and the reaction is stirred for 3 to 20 hours to allow the polyacrylic acid to undergo an addition polymerization reaction with the second grafted carrier, so that the polyacrylic acid is linked to the acryloyl group, forming a second grafted layer on the surface of the carrier, thus preparing a multifunctional adsorbent.

[0070] More specifically, the second grafted support was added to DMF for swelling treatment for 10 to 24 hours, followed by the addition of ammonium persulfate and the temperature was raised to 30°C to 80°C. Under a protective atmosphere of continuous nitrogen purging, polyacrylic acid was slowly added dropwise (at a rate of 1 mL / min to 2 mL / min), and the reaction was magnetically stirred for 3 to 20 hours to graft polyacrylic acid onto the second grafted support. After the reaction was completed, the reaction product was washed with water for injection and methanol, and then dried in a vacuum drying oven at 10°C to 50°C to constant weight to prepare a multifunctional adsorbent, namely tryptophan, polyacrylic acid grafted polystyrene-epoxy resin microspheres.

[0071] Based on the above embodiments, as an optional implementation, the mass ratio of the second grafting carrier, DMF (N,N-dimethylformamide), ammonium persulfate, and polyacrylic acid is 1:(1-5):(0.1-1):(2-20). Thus, DMF, as a solvent, within the above range, can both swell the second grafting carrier and effectively dissolve polyacrylic acid and ammonium persulfate, creating a single and homogeneous medium environment for the multi-component reaction and reducing side reactions. Ammonium persulfate, as a free radical initiator, within the above range, can provide a sufficient minimum free radical concentration to initiate graft polymerization, avoiding side reactions caused by excessive free radical initiator (such as increased homopolymer, excessively long graft chains, or crosslinking), and can also generate sufficient free radicals to ensure the initiation of a large number of graft chains in a short time, improving graft density and reaction efficiency. The polyacrylic acid content within the above range, and the relatively wide range of polyacrylic acid content, allows those skilled in the art to significantly control the grafting amount.

[0072] The preparation method of the multifunctional adsorbent provided in this embodiment uses polystyrene-epoxy resin as a carrier. The surface of polystyrene-epoxy resin has a large number of epoxy active groups. Tryptophan can be grafted onto the carrier through a nucleophilic addition reaction, so that the epoxy active groups and tryptophan are connected by chemical bonds. After tryptophan is grafted onto the carrier, the epoxy groups on the surface of the carrier form hydroxyl groups through ring opening. After the newly formed hydroxyl groups undergo an acrylylation reaction, acryloyl groups can be introduced onto the carrier. Then, polyacrylic acid is grafted onto the carrier through an addition polymerization reaction, so that polyacrylic acid and acryloyl groups are connected by chemical bonds. The preparation method of this embodiment grafts tryptophan and polyacrylic acid onto the outer layer of the carrier. With the cooperation of the carrier, tryptophan, and polyacrylic acid, simultaneous adsorption of LDL-C, inflammatory factors, and FIB can be achieved, effectively reducing LDL-C, inflammatory factors, and FIB in the blood. Furthermore, the polystyrene-epoxy resin is chemically bonded to both tryptophan and polyacrylic acid, ensuring a strong bond between them. This reduces the risk of tryptophan and polyacrylic acid detachment, thus ensuring the safety of the multifunctional adsorbent. In addition, the preparation method provided in this embodiment has relatively few reaction steps, a relatively simple preparation process, mild reaction conditions, high safety during the reaction process, and low production cost, making it suitable for industrial production.

[0073] A third aspect of this application provides a perfusion device comprising the multifunctional adsorbent described in the first aspect, or comprising a multifunctional adsorbent prepared by the preparation method described in the second aspect, wherein the multifunctional adsorbent can be filled in the perfusion device, and the perfusion device is used for the adsorption of FIB, LDL-C and inflammatory factors during extracorporeal blood circulation.

[0074] The perfusion device provided in this embodiment includes the aforementioned multifunctional adsorbent, which can simultaneously adsorb FIB, LDL-C, and key inflammatory factors in the patient's blood circulation. This reduces the hypercoagulable state of the blood, improves lipid metabolism, and inhibits excessive inflammatory responses. From a pathophysiological perspective, it improves the microcirculation and inflammatory state of the lower limb veins, promotes ulcer healing, and thus provides an effective and significantly improved clinical prognosis solution for CLTI patients who cannot undergo revascularization. Furthermore, the multifunctional adsorbent in this perfusion device has virtually no impact on beneficial plasma components, and will not affect the treatment efficacy or patient safety.

[0075] To provide a more detailed description of the present invention, specific embodiments will be used to further illustrate the invention. Unless otherwise specified, the experimental methods used in the embodiments of the present invention are conventional methods; unless otherwise specified, the materials and reagents used in the embodiments of the present invention are commercially available.

[0076] Example 1

[0077] This embodiment provides a multifunctional adsorbent, which is prepared by the following method:

[0078] (1) Grafting tryptophan onto the carrier: Polystyrene-epoxy resin microspheres were weighed as the carrier. The carrier was washed 6 times with 50% ethanol and then 7 times with water to obtain the cleaned carrier. 20g of tryptophan was weighed and dissolved in 50mL of 2mol / L sodium hydroxide solution. Then, a 0.1mol / L carbonate buffer solution with pH 10.5 was added to prepare a tryptophan solution. The cleaned carrier was added to the tryptophan solution, with a volume ratio of 1:5 between the carrier and the tryptophan solution. The reaction was then carried out at 30℃ for 5 hours to graft tryptophan onto the surface of the carrier. After the reaction was completed, the reaction product was washed with water until neutral to obtain the first grafted carrier, i.e., the tryptophan-grafted carrier.

[0079] (2) Introducing acryloyl groups into the support: Weigh the first grafted support, add anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride to the first grafted support, wherein the mass ratio of the first grafted support, anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride is 1:10:2:2; then, after stirring the reaction at 20°C for 6 hours, add water for injection to terminate the reaction, and introduce acryloyl groups onto the first grafted support. After the reaction is completed, wash the reaction product with anhydrous ethanol, distilled water and methanol 8 times in sequence, and dry it under vacuum at 40°C to constant weight to obtain the second grafted support, that is, the acryloylated support.

[0080] (3) Grafting polyacrylic acid onto the carrier: Weigh the second graft carrier and add it to DMF for swelling treatment for 24 h. Then add ammonium persulfate and heat to 80 °C. Under the protective atmosphere of continuous nitrogen gas, slowly add polyacrylic acid. The mass ratio of the second graft carrier, DMF (N,N-dimethylformamide), ammonium persulfate and polyacrylic acid is 1:1:0.1:2. Then, stir the reaction magnetically for 20 h to graft polyacrylic acid onto the second graft carrier. After the reaction is completed, wash the reaction product with water for injection and methanol, and dry it in a vacuum drying oven at 30 °C to constant weight to prepare a multifunctional adsorbent, namely tryptophan and polyacrylic acid grafted polystyrene-epoxy resin microspheres.

[0081] Example 2

[0082] This embodiment provides a multifunctional adsorbent, which is prepared by the following method:

[0083] (1) Grafting tryptophan onto the carrier: Polystyrene-epoxy resin microspheres were weighed as the carrier. The carrier was washed 6 times with 50% ethanol and then 7 times with water to obtain the cleaned carrier. 15g of tryptophan was weighed and dissolved in 20mL of 1mol / L sodium hydroxide solution. Then, 0.1mol / L carbonate buffer solution with pH 10.5 was added to prepare a tryptophan solution. The cleaned carrier was added to the tryptophan solution with a volume ratio of 1:3 between the carrier and the tryptophan solution. The reaction was then carried out at 40℃ for 8 hours to graft tryptophan onto the surface of the carrier. After the reaction was completed, the reaction product was washed with water until neutral to obtain the first grafted carrier, i.e., the tryptophan-grafted carrier.

[0084] (2) Introducing acryloyl groups into the support: Weigh the first grafted support, add anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride to the first grafted support, wherein the mass ratio of the first grafted support, anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride is 1:20:3:2; then, after stirring the reaction at 50°C for 5 hours, add water for injection to terminate the reaction, and introduce acryloyl groups onto the first grafted support. After the reaction is completed, wash the reaction product three times with anhydrous ethanol, distilled water and methanol in sequence, and dry it under vacuum at 20°C to constant weight to obtain the second grafted support, that is, the acryloylated support.

[0085] (3) Grafting polyacrylic acid onto the carrier: Weigh the second graft carrier and add it to DMF for swelling treatment for 10 h. Then add ammonium persulfate and heat to 30 °C. Under the protective atmosphere of continuous nitrogen gas, slowly add polyacrylic acid. The mass ratio of the second graft carrier, DMF (N,N-dimethylformamide), ammonium persulfate and polyacrylic acid is 1:1:0.5:10. Then, stir the reaction magnetically for 10 h to graft polyacrylic acid onto the second graft carrier. After the reaction is completed, wash the reaction product with water for injection and methanol and dry it in a vacuum drying oven at 40 °C to constant weight to prepare a multifunctional adsorbent, namely tryptophan and polyacrylic acid grafted polystyrene-epoxy resin microspheres.

[0086] Example 3

[0087] This embodiment provides a multifunctional adsorbent, which is prepared by the following method:

[0088] (1) Grafting tryptophan onto the carrier: Polystyrene-epoxy resin microspheres were weighed as the carrier. The carrier was washed 6 times with 50% ethanol and then 7 times with water to obtain the cleaned carrier. 10g of tryptophan was weighed and dissolved in 40mL of 2mol / L sodium hydroxide solution. Then, 0.1mol / L carbonate buffer solution with pH 10.5 was added to prepare a tryptophan solution. The cleaned carrier was added to the tryptophan solution with a volume ratio of 1:10 between the carrier and the tryptophan solution. The reaction was then carried out at 30℃ for 10 hours to graft tryptophan onto the surface of the carrier. After the reaction was completed, the reaction product was washed with water until neutral to obtain the first grafted carrier, i.e., the tryptophan-grafted carrier.

[0089] (2) Introducing acryloyl groups into the support: Weigh the first grafted support, add anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride to the first grafted support, wherein the mass ratio of the first grafted support, anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride is 1:30:4:5; then, after stirring the reaction at 40°C for 6 hours, add water for injection to terminate the reaction, and introduce acryloyl groups onto the first grafted support. After the reaction is completed, wash the reaction product with anhydrous ethanol, distilled water and methanol 5 times in sequence, and dry it under vacuum at 30°C to constant weight to obtain the second grafted support, that is, the acryloylated support.

[0090] (3) Grafting polyacrylic acid onto the carrier: Weigh the second graft carrier and add it to DMF for swelling treatment for 12 h. Then add ammonium persulfate and heat to 60 °C. Under the protective atmosphere of continuous nitrogen gas, slowly add polyacrylic acid. The mass ratio of the second graft carrier, DMF (N,N-dimethylformamide), ammonium persulfate and polyacrylic acid is 1:5:0.5:20. Then, stir magnetically for 20 h to graft polyacrylic acid onto the second graft carrier. After the reaction is completed, wash the reaction product with water for injection and methanol and dry it in a vacuum drying oven at 20 °C to constant weight to prepare a multifunctional adsorbent, namely tryptophan and polyacrylic acid grafted polystyrene-epoxy resin microspheres.

[0091] Example 4

[0092] This embodiment provides a multifunctional adsorbent, which is prepared by the following method:

[0093] (1) Grafting tryptophan onto the carrier: Polystyrene-epoxy resin microspheres were weighed as the carrier. The carrier was washed 6 times with 50% ethanol and then 7 times with water to obtain the cleaned carrier. 10g of tryptophan was weighed and dissolved in 50mL of 1mol / L sodium hydroxide solution. Then, 0.1mol / L carbonate buffer solution with pH 10.5 was added to prepare a tryptophan solution. The cleaned carrier was added to the tryptophan solution with a volume ratio of 1:8 between the carrier and the tryptophan solution. The reaction was then carried out at 40℃ for 6 hours to graft tryptophan onto the surface of the carrier. After the reaction was completed, the reaction product was washed with water until neutral to obtain the first grafted carrier, i.e., the tryptophan-grafted carrier.

[0094] (2) Introducing acryloyl groups into the support: Weigh the first grafted support, add anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride to the first grafted support, wherein the mass ratio of the first grafted support, anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride is 1:20:5:5; then, after stirring the reaction at 50°C for 5 hours, add water for injection to terminate the reaction, and introduce acryloyl groups onto the first grafted support. After the reaction is completed, wash the reaction product with anhydrous ethanol, distilled water and methanol 6 times in sequence, and dry it under vacuum at 25°C to constant weight to obtain the second grafted support, that is, the acryloylated support.

[0095] (3) Grafting polyacrylic acid onto the carrier: Weigh the second graft carrier and add it to DMF for swelling treatment for 20 h. Then add ammonium persulfate and heat to 40 °C. Under the protective atmosphere of continuous nitrogen gas, slowly add polyacrylic acid. The mass ratio of the second graft carrier, DMF (N,N-dimethylformamide), ammonium persulfate and polyacrylic acid is 1:2:0.6:10. Then, stir the reaction magnetically for 10 h to graft polyacrylic acid onto the second graft carrier. After the reaction is completed, wash the reaction product with water for injection and methanol, and dry it in a vacuum drying oven at 40 °C to constant weight to prepare a multifunctional adsorbent, namely tryptophan and polyacrylic acid grafted polystyrene-epoxy resin microspheres.

[0096] Comparative Example 1

[0097] Take 20 mL of polyacrylic acid carrier resin and epoxidize it using epichlorohydrin or 1,4-butanediol diglycidyl ether, controlling the pH to 8-11. React at 30℃ for 3 h to obtain the epoxidized carrier. Purify the epoxidized carrier with purified water until the pH is neutral. Mix the epoxidized carrier with an amination agent at a volume ratio of 1:(2-6) and react at 30℃ for 1.5 h to amination the carrier. The amination agent includes ammonia, ethylenediamine, 1,2-propanediamine, or 1,3-propanediamine. Wash the carrier with purified water until the pH is neutral. Mix the amination carrier with polyacrylic acid and EEDQ at a mass ratio of 10:0.2:0.1, controlling the pH to 3-7, and react at room temperature for 12 h to immobilize the polyacrylic acid ligand onto the carrier. Wash and purify the adsorbent to obtain the LDL adsorbent.

[0098] Test case

[0099] The adsorption performance of the multifunctional adsorbents prepared in Examples 1 to 4 and Comparative Example 1 on FIB, LDL-C, and inflammatory factors was tested. The specific test methods are as follows:

[0100] 1 mL of the multifunctional adsorbent from Examples 1 to 4 and Comparative Example 1 was accurately measured and added to 10 mL of human plasma. After adsorption at 37°C with shaking in the dark for 2 hours, the adsorption was completed. The supernatant was then aspirated to determine the concentrations of FIB, LDL-C, and inflammatory factors (represented by IL-6). The adsorption rate of the multifunctional adsorbent in each example and comparative example was calculated. The formula for calculating the adsorption rate of the multifunctional adsorbent is: Adsorption rate = [(m1-m2) / m1] × 100%, where m1 is the concentration of each substance in the plasma before adsorption, and m2 is the concentration of each substance in the plasma after adsorption with the adsorbent. The adsorption rates of the multifunctional adsorbent for FIB, LDL-C, and inflammatory factors in each example and comparative example are shown in Table 1.

[0101] Table 1

[0102]

[0103] As shown in Table 1, compared to the polyacrylic acid resin grafted with polyacrylic acid in Comparative Document 1, the multifunctional adsorbents in Examples 1 to 4 of this application exhibit better adsorption performance for FIB, LDL-C, and IL-6 after plasma adsorption. In contrast, the adsorbent in Comparative Example 1 shows better adsorption of LDL but no adsorption effect on FIB and IL-6. Therefore, this application uses polystyrene-epoxy resin as a carrier, which can adsorb inflammatory factors through molecular sieving, van der Waals forces, and lipophilic-hydrophobic interactions. By grafting tryptophan onto the outer layer, it can specifically adsorb inflammatory factors (such as IL-1β, IL-6) and fibrinogen containing aromatic rings or hydrophobic regions. By grafting polyacrylic acid onto the outer layer, it can specifically adsorb LDL-C. The multifunctional adsorbent provided in this application can simultaneously adsorb LDL-C, inflammatory factors, and FIB, effectively reducing LDL-C, inflammatory factors, and FIB in the blood.

[0104] While the disclosure is as stated above, its scope of protection is not limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of this disclosure, and all such changes and modifications will fall within the protection scope of this invention.

Claims

1. A multifunctional adsorbent, characterized in that, Includes a carrier and a functional layer disposed on the outer layer of the carrier; The carrier is polystyrene-epoxy resin; The functional layer consists of a first grafted layer and a second grafted layer. The first grafted layer is formed by reacting tryptophan with the epoxy groups of the carrier, and the second grafted layer is formed by reacting polyacrylic acid with acryloyl groups introduced on the carrier.

2. The multifunctional adsorbent according to claim 1, characterized in that, The first graft layer is formed by covalently linking the tryptophan with the epoxy group of the support through a nucleophilic addition reaction, and the second graft layer is formed by the polyacrylic acid with the acryloyl group introduced on the support through an addition polymerization reaction, wherein the acryloyl group is introduced after acrylating the support.

3. The multifunctional adsorbent according to claim 1, characterized in that, The grafting rate of tryptophan on the multifunctional adsorbent is 50 wt% to 100 wt%, and the grafting rate of polyacrylic acid is 50 wt% to 100 wt%.

4. The multifunctional adsorbent according to claim 1, characterized in that, The carrier has a particle size between 0.3 mm and 0.8 mm, an average pore size between 7 nm and 20 nm, and a pore volume of 0.8 cm³. 3 / g to 1.5cm 3 / g, specific surface area is 300m² 2 / g to 600m 2 / g, with an epoxy content ranging from 0.03 mmol / ml to 0.1 mmol / ml.

5. A method for preparing a multifunctional adsorbent, characterized in that, The preparation of the multifunctional adsorbent according to any one of claims 1 to 4 comprises the following steps: Polystyrene-epoxy resin is provided as a carrier; The epoxy groups on the support are reacted with tryptophan to form a first grafting layer on the surface of the support, thereby obtaining a first grafted support. Acrylyl groups were introduced onto the first grafting support to prepare a second grafting support. The acryloyl groups on the second grafted carrier are reacted with polyacrylic acid to form a second grafted layer on the surface of the carrier, thereby obtaining the multifunctional adsorbent.

6. The method for preparing the multifunctional adsorbent according to claim 5, characterized in that, The process of reacting the epoxy groups on the support with tryptophan to form a first graft layer on the surface of the support, thereby obtaining a first grafted support, includes: The tryptophan was prepared into a tryptophan solution; The carrier and the tryptophan solution are mixed at a volume ratio of 1:(1-10) and reacted with shaking at 20°C to 50°C for 2 to 10 hours to connect the tryptophan with epoxy groups, thereby forming the first grafted layer on the surface of the carrier and obtaining the first grafted carrier.

7. The method for preparing the multifunctional adsorbent according to claim 6, characterized in that, Preparing the tryptophan into a tryptophan solution includes: The tryptophan was dissolved in a sodium hydroxide solution, and then a carbonate buffer solution with a pH of 9 to 12 was added to prepare a tryptophan solution. The concentration of the carbonate buffer solution was 0.05 mol / L to 2 mol / L.

8. The method for preparing the multifunctional adsorbent according to claim 5, characterized in that, The step of introducing acryloyl groups onto the first grafting support to obtain the second grafting support includes: Anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride were added to the first grafting carrier. After stirring and reacting at 20°C to 50°C for 3 to 8 hours, water for injection was added to terminate the reaction. Acryloyl groups were introduced onto the first grafting carrier to obtain the second grafting carrier. The mass ratio of the first grafting carrier, anhydrous dichloromethane, acryloyl chloride and anhydrous aluminum trichloride is 1:(10-40):(2-5):(2-5).

9. The method for preparing the multifunctional adsorbent according to claim 5, characterized in that, The process of reacting the acryloyl groups on the second grafted support with polyacrylic acid to form a second grafted layer on the surface of the support to obtain the multifunctional adsorbent includes: The second grafted carrier is added to DMF for swelling treatment, then ammonium persulfate is added, and the temperature is raised to 30°C to 80°C. Under a protective atmosphere of continuous nitrogen gas, polyacrylic acid is slowly added dropwise and stirred for 3 to 20 hours to allow the polyacrylic acid to react with acryloyl groups and form a second grafted layer on the surface of the carrier, thus obtaining the multifunctional adsorbent. The mass ratio of the second grafting carrier, DMF, ammonium persulfate and polyacrylic acid is 1:(1-5):(0.1-1):(2-20).

10. An irrigation device, characterized in that, The perfusion device includes a multifunctional adsorbent as described in any one of claims 1 to 4, or a multifunctional adsorbent prepared by the preparation method described in any one of claims 5 to 9, and is used for the adsorption of FIB, LDL-C and inflammatory factors during extracorporeal blood circulation.

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