Blood purification and anticoagulation function polyether sulfone-based material, preparation method and application thereof

Abstract

This invention relates to the field of biomedical polymer materials technology, specifically to a polyethersulfone-based material with blood purification and anticoagulation functions, its preparation method, and its applications. The polyethersulfone-based material uses polyethersulfone as the main component, and a stable multi-coordination network structure is constructed by introducing terpyridine ligands and multivalent metal ions at the molecular level. Furthermore, the anticoagulant active molecules argatroban or heparin are immobilized on its surface, achieving selective adsorption of blood toxins and synergistic regulation of the anticoagulation reaction. The material is prepared using a process combining phase inversion membrane formation technology and surface coordination modification, resulting in a composite interface on the membrane surface rich in hydrophilic groups and a stable anticoagulant layer, significantly improving blood compatibility and membrane flux stability. This composite membrane can simultaneously perform purification and anticoagulation functions in hemodialysis, hemofiltration, and extracorporeal circulation systems, exhibiting good mechanical strength, chemical stability, and biosafety. The preparation route of this invention is simple, the parameters are controllable, and it is suitable for large-scale production.

Description

Technical Field

[0001] This invention relates to the field of biomedical polymer materials technology, specifically to a polyethersulfone-based material with blood purification and anticoagulation functions, its preparation method, and its application. Background Technology

[0002] Blood purification technology is an important clinical treatment for renal failure, liver dysfunction, metabolic disorders, and poisoning. Its core material is a medical polymer membrane with excellent separation performance and biocompatibility. Currently, widely used blood purification membrane materials include polyethersulfone (PES), polysulfone (PSF), and polyacrylonitrile (PAN). These materials possess good mechanical strength and chemical stability, but they suffer from problems such as strong hydrophobicity, severe protein adsorption, and insufficient blood compatibility, easily causing platelet adhesion and coagulation reactions, leading to decreased membrane flux, shortened lifespan, and increased risk of patient complications. Therefore, developing polymer membrane materials that combine high-efficiency purification performance with anticoagulation function has become a key research focus in the field of blood purification.

[0003] Traditional modification strategies primarily involve introducing hydrophilic groups such as hydroxyl, carboxyl, and sulfonic acid groups onto the membrane surface, or doping with hydrophilic polymers such as polyvinylpyrrolidone and polyethylene glycol, to improve hydrophilicity and antifouling properties. However, these physical modification methods suffer from weak binding force and poor durability, easily leading to problems such as modified layer detachment or diminished anticoagulant effect during long-term cyclic use. On the other hand, commonly used anticoagulants such as heparin or citric acid require exogenous addition, which presents limitations such as difficulty in controlling dosage and the risk of bleeding due to excessive dosage. Summary of the Invention

[0004] To address the problems of insufficient hydrophilicity, limited anticoagulation performance, and poor stability of surface modification layers in existing blood purification membrane materials, this invention provides a polyethersulfone-based material with both blood purification and anticoagulation functions, along with its preparation method and applications. By introducing terpyridine ligands into the polyethersulfone host molecule and forming a stable multi-coordination network structure with multivalent metal ions, and then immobilizing anticoagulation active molecules on the membrane surface, the synergistic regulation of efficient removal of blood toxins and anticoagulation reaction is achieved.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows.

[0006] The first objective of this invention is to provide a polyethersulfone-based material with blood purification and anticoagulation functions, wherein the polyethersulfone-based material has any one of the structural formulas (1) to (3); Equation (1) Equation (2), Equation (3); Where n is 300–800, M is a soluble metal salt, and R is an anticoagulant.

[0007] This invention introduces synergistic multivalent metal ions and utilizes the amidation coupling reaction between acylpyridine-containing organic ligands and amino-modified polyethersulfone to construct a stable multi-coordination network structure within a polyethersulfone matrix, significantly improving the material's surface hydrophilicity, charge transfer efficiency, and biocompatibility. This invention not only expands the application boundaries of polyethersulfone-based materials in blood purification and extracorporeal circulation but also provides a theoretical basis and technical support for the development of novel, efficient, and safe medical blood purification membrane materials.

[0008] In another preferred embodiment, the anticoagulant is argatroban or heparin; The soluble metal salt is any one of zinc nitrate, silver hexafluorophosphate, and ferric chloride.

[0009] A second aspect of this invention provides a method for preparing the polyethersulfone-based material with blood purification and anticoagulation functions, comprising the following steps: Using pyridine and polyethersulfone as raw materials, a grafting reaction was carried out in the first reaction solvent system to obtain pyridine-polyethersulfone ligands; Using pyridine-polyethersulfone ligands and soluble metal salts as raw materials, a first coordination reaction was carried out in a second reaction solvent system to obtain metal ligands; Using metal ligands and anticoagulant drugs as raw materials, a second coordination reaction is carried out in a third reaction solvent system to obtain a polyethersulfone-based material with dual functions of blood purification and anticoagulation.

[0010] In another preferred embodiment, the mass ratio of the pyridine ligand to the polyethersulfone is 1 to 2:1, the grafting reaction temperature is 25°C to 45°C, and the time is 8 to 22 hours.

[0011] In another preferred embodiment, the mass ratio of pyridine ligand to polyethersulfone is 1 to 2:1, the grafting reaction temperature is 25°C to 45°C, and the time is 8 to 22 hours.

[0012] It should be noted that the pyridine ligand is preferably an acyl-bispyridine organic ligand. This invention uses polyethersulfone as the main backbone, grafting pyridine groups onto the amino-modified polyethersulfone, i.e., the NH2-PES backbone. In the first step, dichloromethane was used as the solvent system. Under the condition of amidation grafting reaction between the acyl and amino groups, a well-defined and chemically stable bispyridine-polyethersulfone organic polymer was successfully constructed. This polymer is the pyridine-polyethersulfone ligand described in this invention. In the pyridine-polyethersulfone ligand, the pyridine groups are uniformly distributed on the polyethersulfone molecular chain, providing controllable coordination sites and an excellent electron transport environment for subsequent metal ion coordination.

[0013] In another preferred embodiment, the mass ratio of pyridine-polyethersulfone ligand to soluble metal salt is 1:1 to 3, the temperature of the first coordination reaction is 25°C to 55°C, and the time is 8h to 20h.

[0014] It should be noted that after the first amidation grafting reaction is completed, a pyridine-polyethersulfone ligand with a well-defined structure is obtained. Based on this, Zn is further introduced into the system by adjusting the solvent polarity, reaction temperature, and the ratio of metal to ligand. 2+ Fe 3+ Ag + A soluble metal salt serves as the coordination center, initiating the first-step coordination interaction with the pre-formed pyridine-polyethersulfone ligand. Ethanol is used as the solvent in this reaction system, and under mild conditions, the metal center structure is precisely controlled through the first-step coordination reaction between dipyridine and the metal ion, successfully constructing a stable multi-coordination network structure within the polyethersulfone framework. This structure significantly enhances the material's surface hydrophilicity, charge conductivity, and biocompatibility. The resulting material can be prepared into a membrane using a simple solvent phase inversion method, exhibiting characteristics such as uniform membrane structure, controllable composition, and excellent resistance to protein adsorption and anticoagulation, demonstrating promising application potential in blood purification and extracorporeal circulation systems.

[0015] In another preferred embodiment, the mass ratio of the metal ligand to the anticoagulant is 1:4 to 10, and the in-situ reaction time is 25°C to 30°C for 4 to 8 hours.

[0016] It should be noted that this step in the present invention is a coordination reaction between the metal complex and the anticoagulant drug. Based on this, the anticoagulant drug argatroban or heparin is introduced to allow it to coordinate in situ with the metal center. N,N-dimethylformamide (DMF) is used as the solvent, and the reaction is carried out at 25°C–30°C with stirring for 4–8 hours to achieve a stable complexation between the anticoagulant molecule and the metal ion. During this process, the amide, carboxyl, or guanidine functional groups in the anticoagulant drug molecule can form coordination or ionic bonds with the metal center, thereby forming a dense and stable anticoagulant active layer on the surface of the metal complex. This structure effectively prevents the loss of anticoagulant molecules and improves its chemical stability and biological activity in the blood contact environment. The composite material prepared using the polyethersulfone-based material of the present invention forms a composite interface on the surface of which the metal complex layer and the anticoagulant functional layer coexist. During blood purification, it exhibits both highly efficient adsorption and sustained anticoagulant functions, significantly improving the material's blood compatibility and long-term safety.

[0017] In another preferred embodiment, the method for preparing pyridine-polyethersulfone includes the following steps: Using acylpyridine as the acylation unit and amino-modified polyethersulfone as the nucleophilic unit, an amidation coupling reaction was carried out under alkaline conditions and an acyl chloride acylation reaction system in an inert gas protection environment to obtain pyridine-polyethersulfone ligands.

[0018] The acylpyridine ligands provided by this invention are acyl monopyridine, acyl dipyridine, or acyl tripyridine, and the structural formula of the acyl monopyridine is shown in formula (4): Equation (4).

[0019] The structural formula of acylbispyridine is shown in formula (5): Equation (5).

[0020] The structural formula of acyl-terpyridine is shown in formula (6): Equation (6).

[0021] It should be noted that the acylpyridine ligands provided by the present invention include acyl monopyridine, acyl dipyridine and acyl tripyridine structural types.

[0022] In the preparation of the pyridine-polyethersulfone ligand of this invention, an amidation coupling reaction was employed to achieve efficient bonding between the acylpyridine structure and the polyethersulfone skeleton. This reaction, through the directional coupling of the acyl and amino groups, involves reacting the acylpyridine derivative with the aminated polyethersulfone NH2-PES in an anhydrous dichloromethane system and under the activation conditions of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, forming a stable amide bond structure. This yields a well-defined pyridine-polyethersulfone organic polymer ligand with good conjugation. Simultaneously, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide also serves as a desiccant for water removal. This synthetic strategy offers advantages such as mild reaction conditions, simple operation, and high selectivity. It effectively extends the π-conjugated electronic structure within the system, significantly improving the electronic delocalization ability and chemical stability of the molecular skeleton. The obtained pyridine-polyethersulfone ligand not only maintains the excellent mechanical and film-forming properties of polyethersulfone materials, but also endows them with excellent metal coordination activity and electronic conduction properties, laying a solid foundation for the subsequent construction of multi-metal synergistic coordination network structures and blood purification-anticoagulation composite membranes.

[0023] To achieve effective separation and purification of the pyridine-polyethersulfone product, this invention first employs dichloromethane filtration after the reaction to remove unreacted raw materials and byproducts, yielding a pale yellow lumpy solid. Subsequently, the obtained solid is directly dissolved or dispersed in a methanol solution, followed by ultrasonic dispersion for 30 minutes to promote impurity desorption and homogenization. This is then repeated under reduced pressure filtration to obtain a pale yellow powder. Finally, the powder is vacuum-dried at 50°C for 20 hours to remove residual solvent and trace impurities, yielding a high-purity, structurally stable white powder of pyridine-polyethersulfone ligand with a terpyridine structure. This purification process is simple to operate, highly reproducible, and effectively improves the purity and crystallinity of the product, providing high-quality organic ligand raw materials for subsequent metal coordination and film formation.

[0024] When the acylpyridine is a monopyridine, the structural formula of the pyridine-polyethersulfone ligand is shown in formula (7): Equation (7).

[0025] When the acylpyridine is a dipyridine, the structural formula of the pyridine-polyethersulfone ligand is shown in formula (8): Equation (8).

[0026] When the acylpyridine is tripyridine, the structural formula of the pyridine-polyethersulfone ligand is shown in formula (9): Equation (9).

[0027] When the acylpyridine is monopyridine and the metal M is Ag, the structural formula of the metal ligand is shown in formula (10): Equation (10).

[0028] When the acylpyridine is a bispyridine and the metal M is Zn, the structural formula of the metal ligand is shown in formula (11): Equation (11).

[0029] When the acylpyridine is terpyridine and the metal M is Fe, the structural formula of the metal ligand is shown in formula (12): Equation (12).

[0030] In another preferred embodiment, the mass ratio of pyridine ligand to polyethersulfone is 1 to 2:1, the grafting reaction temperature is 25°C to 45°C, and the time is 8 to 22 hours.

[0031] It should be noted that the acyl chloride reaction uses a pyridine derivative containing a carboxyl group as an acidic substrate and thionyl chloride as a chlorinating agent. The carboxyl group is activated to generate the corresponding acyl chloride under anhydrous conditions and inert gas protection. The reaction rate can be significantly increased and the probability of side reactions reduced by thionyl chloride with the catalytic addition of N,N-dimethylformamide.

[0032] In one specific embodiment, the preparation process of the acyl chloride reaction is as follows: Carboxylated monopyridine, anhydrous thionyl chloride, and a catalytic amount of N,N-dimethylformamide were added to a dry three-necked flask. The flask was connected to a reflux condenser and tail gas absorption device (alkali absorption bottle). The mixture was pre-activated by stirring in an ice bath for 10-15 minutes, followed by nitrogen purging. After evacuation and nitrogen backfilling cycles 2-3 times, the mixture was heated to 70-80°C under a nitrogen atmosphere with slight reflux for 1-3 hours. SO2 and HCl gases were continuously released during the reaction. Once the raw materials were largely converted, heating was stopped, and the mixture was cooled to room temperature. Excess thionyl chloride was slowly evaporated under reduced pressure. To completely remove residual thionyl chloride and N,N-dimethylformamide, anhydrous toluene or anhydrous dichloromethane could be added for two co-evaporations. The resulting light-colored solid was the target acyl chloride monopyridine, which could be directly used in the subsequent condensation reaction with amino-modified polyethersulfone under an inert atmosphere and anhydrous conditions. By selecting different carboxypyridine substrates, such as carboxybispyridine or 4-carboxyterpyridine, and controlling the molar ratio, position-selective pyridine acyl chloride products can be obtained. These acylpyridine ligands possess excellent electronic regulation and structural coordination properties. The conjugated system formed by the acyl group and the pyridine ring endows the molecule with strong electronic delocalization effects and N,O bidentate coordination capabilities, significantly enhancing its stability and coordination strength when forming complexes with transition metal ions. This structure not only facilitates electronic coupling and synergistic effects between metal centers but also promotes ordered self-assembly through molecular planarization and π–π stacking, providing an ideal ligand basis for the subsequent construction of multifunctional metal-organic frameworks, optoelectronic functional materials, and molecular recognition systems.

[0033] The third objective of this invention is to provide the application of the aforementioned polyethersulfone-based material with blood purification and anticoagulation functions in hemodialysis and hemofiltration, so as to achieve synergistic regulation of blood toxin removal and anticoagulation reaction.

[0034] Compared with the prior art, the present invention has the following beneficial effects: This invention is the first to introduce a terpyridine ligand and a multivalent metal ion Zn into the main molecular structure of polyethersulfone. 2+ Fe 3 + Ag +A stable multi-coordination network structure is formed, realizing the integrated design of blood purification and anticoagulation functions. Compared with traditional physical doping or surface coating modification methods, this invention improves the structural stability and long-term anticoagulation performance of the material at the molecular level through the dual fixation of chemical bonds and coordination bonds, avoiding problems such as easy shedding of the modified layer and attenuation of anticoagulation effect.

[0035] The highly π-conjugated structure of the terpyridine ligand results in a uniform electron cloud density distribution on the composite membrane surface, significantly enhancing electronic coupling and synergistic effects between metal ions. This improves the charge conduction efficiency of the membrane surface and the selective adsorption capacity for small molecule toxins in the blood. Through the tunable valence state of the metal center, the material can efficiently remove small molecule toxins such as urea and creatinine during blood purification, while maintaining excellent mechanical strength and chemical stability.

[0036] This invention further immobilizes the anticoagulant active molecules argatroban or heparin on the membrane surface, forming a stable anticoagulant functional layer through coordination bonds or ionic bonds. This structure effectively prevents the loss of anticoagulant molecules, ensuring long-lasting and stable anticoagulant activity, significantly reducing the amount of exogenous anticoagulants used, thereby reducing the risk of bleeding and improving blood compatibility.

[0037] This invention employs a preparation route combining phase inversion film formation technology and surface coordination modification. The process is simple, parameters are controllable, and the resulting membrane has a uniform structure, adjustable pore size, and excellent flux stability and anti-protein adsorption properties. This preparation process is easily scaled up and industrialized, and is suitable for various clinical applications such as hemodialysis, hemofiltration, and extracorporeal circulation systems.

[0038] This invention successfully achieves synergistic regulation of blood toxin removal and anticoagulation by constructing a composite system of "polyethersulfone skeleton - terpyridine ligand - multi-metal synergistic center - anticoagulation active layer". It is significantly superior to the existing technology in terms of biocompatibility, anticoagulation durability, functional integration and production feasibility, and provides a new technical approach and application basis for the development of high-performance and safe blood purification membrane materials. Attached Figure Description

[0039] Figure 1 This is the NMR spectrum of acyl terpyridine in Example 1 of the present invention.

[0040] Figure 2 This is the NMR spectrum of the acyl bispyridine in Example 1 of the present invention.

[0041] Figure 3 This is the NMR spectrum of the acyl monopyridine in Example 1 of the present invention.

[0042] Figure 4 Visible-ultraviolet spectra of monopyridine-polyethersulfone, dipyridine-polyethersulfone, and tripyridine-polyethersulfone prepared in Example 1 of this invention.

[0043] Figure 5 The XRD patterns are of the monopyridine-polyethersulfone-Ag metal ligand, dipyridine-polyethersulfone-Zn metal ligand, and terpyridine-polyethersulfone-Fe metal ligand prepared in Example 2 of this invention.

[0044] Figure 6 The NMR spectrum of the terpyridine-polyethersulfone prepared in Example 1 of this invention is shown.

[0045] Figure 7 The NMR spectrum is of the bispyridine-polyethersulfone prepared in Example 1 of this invention.

[0046] Figure 8 This is a cross-sectional scanning electron microscope image of the bispyridine-polyethersulfone material prepared in Example 1 of the present invention.

[0047] Figure 9 This is a cross-sectional scanning electron microscope image of the terpyridine-polyethersulfone material prepared in Example 1 of the present invention.

[0048] Figure 10 The images show the BET adsorption diagrams of the terpyridine-polyethersulfone (TPS-P) Fe materials prepared in Example 1 and Example 2 of this invention; where A is the BET adsorption diagram of Example 1 and B is the BET adsorption diagram of Example 2.

[0049] Figure 11 The NMR spectrum is shown for the terpyridine-polyethersulfone-Fe metal ligand prepared in Example 2 of this invention.

[0050] Figure 12 The NMR spectrum is shown for the bispyridine-polyethersulfone-Zn metal ligand prepared in Example 2 of this invention.

[0051] Figure 13 Infrared spectroscopy of the monopyridine-polyethersulfone-Ag metal ligand, the dipyridine-polyethersulfone-Zn metal ligand, and the terpyridine-polyethersulfone-Fe metal ligand prepared in Example 2 of this invention.

[0052] Figure 14 The hemolysis rate diagrams are for the monopyridine-polyethersulfone By-PES, dipyridine-polyethersulfone Bpy-PES, terpyridine-polyethersulfone Tpy-PES, and polyethersulfone PES prepared in Example 1 of this invention. Detailed Implementation

[0053] To enable those skilled in the art to better understand and implement the technical solutions of this invention, the invention is further described below with reference to specific embodiments. However, the embodiments are not intended to limit the invention. Unless otherwise specified, the following test methods and detection methods are conventional methods; unless otherwise specified, the reagents and raw materials are commercially available.

[0054] The present invention will now be described in detail through specific embodiments. These embodiments are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention.

[0055] Immobilizing anticoagulation function on the material surface through chemical or coordination bonds to achieve structurally stable anticoagulation is a key direction for improving the long-term safety and reliability of medical membranes. In recent years, the coordination structures of functionalized ligands and multivalent metal ions have received widespread attention in the fields of catalysis and medical materials. Tripyridine ligands possess excellent metal ion complexing capabilities and can complex with Zn... 2+ Fe 3+ Ag + Plasma forms a stable multi-coordination network structure, giving the material both excellent electron transport properties and surface modulation capabilities. Introducing this type of multi-coordination structure into a polyethersulfone matrix not only enhances the polarity and hydrophilicity of the membrane surface but also endows the material with selective adsorption capacity for toxic small molecules in the blood through the tunable valence states of the metal centers, thus achieving both blood purification and anticoagulation functions. Furthermore, further modification of the coordination layer with anticoagulant active molecules such as argatroban or heparin can achieve sustained anticoagulation through chemical or coordination fixation, reducing the amount of exogenous anticoagulants used and significantly improving blood compatibility.

[0056] Therefore, constructing a composite membrane with polyethersulfone as the main body, introducing a terpyridine-metal ion coordination network, and immobilizing anticoagulant active molecules can not only achieve synergistic regulation of efficient blood toxin removal and anticoagulant performance, but also maintain excellent mechanical stability and chemical durability. Based on the above ideas, this invention proposes a polyethersulfone-based composite membrane with both blood purification and anticoagulant functions, and its preparation method, to solve the technical bottlenecks of existing blood purification membranes in terms of biocompatibility, anticoagulant durability, and functional integration.

[0057] The following is a detailed description of polyethersulfone-based materials with blood purification and anticoagulation functions, their preparation methods, and applications.

[0058] Example 1: This example provides a method for preparing a polyethersulfone-based material with blood purification and anticoagulation functions, including the following steps: S1. Carboxylated terpyridine is obtained through the Kröhnke aldehyde-ketone condensation reaction, as detailed below: 5 g of p-aldehyde benzoic acid was dissolved in 150 mL of ethanol, and 100 mL of 2-acetylpyridine and 4 eq. of sodium hydroxide were added. The mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. Then, 200 mL of ammonia water was added, and the mixture was refluxed under a nitrogen atmosphere for 20 hours. After cooling to room temperature, the mixture was filtered, and the solid ethanol was refluxed 2-3 times, filtered again, and dried in a solid vacuum drying oven at 50 °C for 24 hours. 4.2 g of the white target product was obtained, with a yield of 84%. The preparation reaction route is shown below:

[0059] .

[0060] Synthesis of acylated terpyridine: A vacuum, anhydrous reaction system was constructed and filled with nitrogen. 2g of dried carboxylated terpyridine was dissolved in 20mL of ultra-dry sulfonium chloride solvent and stirred thoroughly. Separately, a vacuum, anhydrous, nitrogen-filled reaction system was constructed, and 10mL of anhydrous N,N-dimethylformamide was added, followed by a well-stirred polyethersulfone solution. The reaction was carried out at 120℃ for 4 hours. The reaction product was repeatedly washed with double-distilled water and dried under vacuum to constant weight to obtain 1.64g of acylated terpyridine, a white solid, with a yield of 82%. The preparation reaction route is shown below:

[0061] The 1H NMR spectrum of carboxy-terpyridine is shown below. Figure 1 As shown, the NMR data are: 1 H NMR (400MHz, CDCl3) δ9.25(d,4H),9.11(s,2H),9.06(d,2H),8.63(t,2H),8.31(d,2H),8.17(d,2H), 8.07(t,2H).

[0062] Synthesis of acylated bispyridine: A vacuum, anhydrous reaction system was constructed and filled with nitrogen. 2g of dried carboxylated bispyridine (purchased from the Anage platform) was dissolved in 15mL of ultra-dry sulfonium chloride solvent and stirred thoroughly. Separately, a vacuum, anhydrous, nitrogen-filled reaction system was constructed, and 10mL of anhydrous N,N-dimethylformamide was added, followed by a well-stirred polyethersulfone solution. The reaction was carried out at 120℃ for 4 hours. The reaction product was repeatedly washed with double-distilled water and dried under vacuum to constant weight to obtain 1.64g of acylated terpyridine, a white solid, with a yield of 82%. The preparation reaction route is shown below:

[0063] The 1H NMR spectrum of carboxy-dipyridine is shown below. Figure 2 As shown, the NMR data are: 1 H NMR (400MHz, CDCl3) δ9.61(s,2H),8.82(d,2H),7.86(d,2H).

[0064] Synthesis of acylated monopyridine: A vacuum, anhydrous reaction system was constructed and filled with nitrogen. 2 g of dried 4-carboxypyridine was dissolved in 15 mL of ultra-dry sulfoxide solvent and stirred thoroughly. Separately, a vacuum, anhydrous, nitrogen-filled reaction system was constructed, and 10 mL of anhydrous N,N-dimethylformamide was added, followed by a well-stirred polyethersulfone solution. The reaction was carried out at 120 °C for 4 h. The reaction product was repeatedly washed with double-distilled water and dried under vacuum to constant weight to obtain acylated terpyridine, a white solid weighing 1.64 g, with a yield of 82%. The preparation reaction route is shown below:

[0065] The 1H NMR spectrum of carboxy-dipyridine is shown below. Figure 3 As shown, the NMR data are: 1 H NMR (400MHz, CDCl3) δ9.02 (d, 2H), 8.22 (d, 2H).

[0066] The terpyridine-polyethersulfone organic ligand was obtained through a peptide coupling reaction, as follows: 2g of amino-modified polyethersulfone and 500mg of acylated terpyridine were dissolved in dichloromethane solvent, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide was added. The mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours at pH 8-9. The precipitate was extracted with diethyl ether and washed repeatedly with double-distilled water to obtain 1.86g of white terpyridine polyethersulfone organic polymer, with a yield of 93%.

[0067] The 1H NMR spectrum of the tripyridine-polyethersulfone organic ligand Figure 6 As shown, the NMR data are: 1 H NMR (400MHz, CDCl3)δ8.84(s,2H),8.79(d,4H),8.72(d,2H),8.31(d,2H),8.25(d,2H),8.07(t,2H),7.56(t,2H),7.26(s,2nH),6.99(d,2nH),6.81(d,2nH).

[0068] The specific synthesis process of the bispyridine-polyethersulfone organic ligand is as follows: The obtained 2g of amino-modified polyethersulfone and 500mg of acylated bispyridine were dissolved in dichloromethane solvent, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) was added. The mixture was stirred at room temperature under nitrogen atmosphere for 16 hours. The precipitate was extracted with diethyl ether and the precipitate was repeatedly washed with double-distilled water to obtain 1.78g of white terpyridine polyethersulfone organic polymer, with a yield of 90%.

[0069] The 1H NMR spectrum of the dipyridine-polyethersulfone organic ligand is as follows: Figure 7 As shown, the NMR data are: 1 H NMR (400MHz, CDCl3) δ8.88(d,4nH),7.92(s,2nH),7.26(s,2nH),6.99(d,2nH),6.80(d,2nH).

[0070] The specific synthesis process of monopyridine-polyethersulfone organic ligands is as follows: S1. Dissolve the obtained 2g of amino-modified polyethersulfone and 400 mg of acylated monopyridine in dichloromethane solvent, add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), and stir the reaction at room temperature for 16 hours under nitrogen atmosphere. Extract the precipitate with diethyl ether, and wash the precipitate repeatedly with double-distilled water to obtain 1.6g of white tripyridine polyethersulfone organic polymer, with a yield of 85%.

[0071] S2. A first coordination reaction is carried out with a terpyridine-polyethersulfone ligand and a soluble trivalent iron compound to obtain a metal ligand, specifically as follows: 500 mg of terpyridine-polyethersulfone ligand was dissolved in 80 mL of chloroform and placed in a constant-pressure dropping funnel. 300 mg of FeCl3•6H2O was dissolved in 80 mL of anhydrous ethanol and added to a 250 mL single-necked round-bottom flask. The mononuclear terpyridine ligand was then added dropwise to the round-bottom flask. After the addition was complete, the mixture was stirred at 25 °C for 6 h. The mixture was then filtered under reduced pressure to obtain a purple solid. 100 mL of methanol was added, and the mixture was sonicated, filtered, and washed. This process was repeated until the filtrate was colorless. The solvent was removed by vacuum drying to obtain 750 mg of the purple solid. The preparation reaction route is shown below:

[0072] The 1H NMR spectrum of the tripyridine-polyethersulfone metal ligand Figure 11 As shown.

[0073] S3. An in-situ reaction was carried out using a metal ligand and the anticoagulant drug argatroban to obtain a bifunctional polyethersulfone material; specifically: 100 mg of the metal ligand obtained from S2 and 10 mg of argatroban were dissolved in 100 mL of LDM and reacted at room temperature for 20 h. After the reaction was stopped, the mixture was filtered under reduced pressure, and the filtrate was removed to obtain a purple solid. The solid was dissolved in methanol, sonicated for 30 min, filtered under reduced pressure, and the purple solid was dried under vacuum at 50 °C for 20 h to obtain 85 mg of purple powder solid product, with a yield of 77%, which is the bifunctional polyethersulfone material. The preparation reaction route is shown below:

[0074] Example 2: This example provides a method for preparing a polyethersulfone-based material with blood purification and anticoagulation functions. The difference from Example 1 is that: 10 mg of the metal ligand obtained in S2 is dissolved in 5 mL of DMF solution, and 2 mg of argatroban is dissolved in 5 mL of 0.05 mol•L⁻¹ solution. -1 The DMF solution was then stirred at room temperature for 20 hours to allow the reaction to proceed via coordination, resulting in a stable bifunctional polyethersulfone material.

[0075] Example 3: This example provides a method for preparing a polyethersulfone-based material with blood purification and anticoagulation functions. The difference from Example 1 is that: 20 mg of the metal ligand obtained in S2 is dissolved in 10 mL of dichloromethane solution, and 5 mg of argatroban is dissolved in 10 mL of 0.05 mol·L⁻¹ solution. -1 The DMF solution was mixed with dichloromethane solution in equal volumes, and then stirred at room temperature for 20 hours to allow the reaction to proceed through coordination, resulting in a stable bifunctional polyethersulfone material.

[0076] Example 4: This example provides a method for preparing a polyethersulfone-based material with blood purification and anticoagulation functions, including the following steps: S2. A first coordination reaction is carried out with a bispyridine-polyethersulfone ligand and a soluble divalent zinc compound to obtain the metal ligand. The specific process is as follows: 500 mg of bispyridine-polyethersulfone ligand was dissolved in 80 mL of chloroform and placed in a constant-pressure dropping funnel. 300 mg of ZnNO3•6H2O was dissolved in 80 mL of anhydrous ethanol and added to a 250 mL single-necked round-bottom flask. The mononuclear terpyridine ligand was then added dropwise to the round-bottom flask. After the addition was complete, the mixture was stirred at 25 °C for 6 h. The mixture was then filtered under reduced pressure to obtain a purple solid. 100 mL of methanol was added and sonicated, followed by filtration and washing. This process was repeated until the filtrate was colorless. The solvent was removed by vacuum drying to obtain 750 mg of a pale yellow solid. The preparation reaction route is shown below:

[0077] .

[0078] The 1H NMR spectrum of the bispyridine-polyethersulfone metal ligand is as follows: Figure 12 As shown.

[0079] S3. An in-situ reaction was carried out using a metal ligand and the anticoagulant drug argatroban to obtain a bifunctional polyethersulfone material; the specific process is as follows: 100 mg of the metal ligand obtained from S2 and 10 mg of argatroban were dissolved in 100 mL of dichloromethane and reacted at room temperature for 20 h. After the reaction was stopped, the mixture was filtered under reduced pressure, and the filtrate was removed to obtain a purple solid. The solid was dissolved in methanol, sonicated for 30 min, filtered under reduced pressure, and the purple solid was dried under vacuum at 50 °C for 20 h to obtain 85 mg of purple powder solid product, with a yield of 77%, which is the bifunctional polyethersulfone material. The preparation reaction route is shown below:

[0080] .

[0081] Figure 4 The UV-Vis absorption spectra of three modified membrane materials, Tpy-PES, Bpy-PES, and by-PES, are presented. All three samples exhibit distinct absorption bands in the 200–350 nm range, while the absorption drops rapidly to near zero after 350 nm, indicating that their main absorption is located in the UV region, which is a typical characteristic of aromatic π–π* transitions.

[0082] The Tpy-PES sample exhibits its strongest absorption peak in the approximately 270 nm–310 nm range, with a maximum absorbance of about 3.8–4.0 and a relatively broad absorption band, indicating that the introduction of the tripyridine Tpy ligand enhances the π–π* electronic transitions in the molecular system. In contrast, Bpy-PES shows its main absorption peak in the 260–300 nm range, with a maximum absorbance of about 3.5, slightly lower than Tpy-PES, and a relatively narrower absorption band, suggesting a weaker conjugation effect of the bispyridine Bpy ligand. The absorption peak of the By-PES sample shifts slightly towards shorter wavelengths, with an absorbance of about 3.0, indicating that its electronic delocalization and conjugation ability are both weaker than the former two.

[0083] Overall, the absorption intensity of the three samples followed the order: Tpy-PES > Bpy-PES > by-PES, with a slight redshift in the absorption peak position of Tpy-PES. This indicates that with the increase of the number of pyridine substituents, the conjugation degree of the system is significantly enhanced, the π–π* transition energy difference decreases, and the intramolecular electron cloud distribution becomes more delocalized. Therefore, it can be inferred that the introduction of the Tpy group not only improves the light absorption capacity of the material but may also provide a favorable electronic structure basis for its subsequent metal coordination or photoelectric response properties.

[0084] Figure 5 X-ray diffraction patterns of metal coordination modified film materials Tpy-PES-Fe, Bpy-PES-Zn, and By-PES-Ag are shown. The diffraction patterns of the three samples do not show obvious sharp diffraction peaks in the 2θ range of 15° to 80°, but only broad and gentle diffuse peaks, indicating that the materials exhibit an amorphous structure overall.

[0085] In the Tpy-PES-Fe sample, the diffraction curve is relatively broad with slight baseline fluctuations, indicating that a strong coordination interaction may have formed between iron ions and the tripyridine ligand, leading to the formation of a locally ordered structure, but the overall state remains predominantly amorphous. The diffraction curve of Bpy-PES-Zn is relatively flat, with no obvious crystalline phase characteristics, indicating that the coordination interaction between zinc ions and the bispyridine ligand did not introduce a clear crystalline structure. The diffraction signal of the By-PES-Ag sample is also dominated by diffuse peaks, and no characteristic diffraction peaks of metallic silver were observed, suggesting that silver ions exist in a highly dispersed or coordinated form in the polymer matrix, rather than precipitated as crystalline silver particles.

[0086] Comprehensive analysis shows that all three metal coordination composite films maintained the amorphous characteristics of the polyethersulfone matrix, indicating that the original molecular chain arrangement was not disrupted during ligand modification and metal ion introduction. The introduction of metal ions mainly achieved structural regulation at the molecular scale through coordination with pyridine-containing groups, rather than altering the macroscopic structure of the material by forming a crystalline phase. This result also provides a structural basis for subsequent research on their optical, electrochemical, and adsorption properties.

[0087] Figure 8 This is a cross-sectional scanning electron microscope image of the bispyridine-polyethersulfone material prepared in Example 2 of the present invention. Figure 8 As can be seen, the material exhibits a uniform and interconnected finger-like pore structure with a relatively regular pore size distribution. The pores are arranged along the film thickness direction, exhibiting a typical asymmetric structure. The smooth and dense pore walls and clear interfaces indicate stable phase separation behavior and a moderate solvent-to-nonsolvent exchange rate during film formation.

[0088] The formation of this structure is closely related to the bispyridine ligand introduction strategy employed in this invention. The presence of pyridine groups enhances the interactions between polymer chains, enabling the material to maintain high structural integrity during solvent exchange, thereby forming a regular pore distribution. This finger-like pore structure not only improves the specific surface area and permeability of the membrane, but also provides abundant coordination sites in the pore wall region, further enhancing the material's ability to adsorb and immobilize metal ions or charged pollutants.

[0089] Figure 9 This is a cross-sectional scanning electron microscope image of the terpyridine-polyethersulfone material prepared in Example 3 of the present invention. Figure 9 As can be seen, this material exhibits a typical asymmetric porous structure, with its cross-section consisting of a dense surface layer and finger-like channels in the lower part. The channels gradually extend from the surface towards the substrate, are closely arranged and evenly distributed, and have thick and independent pore walls, forming a well-structured hierarchical pore structure.

[0090] Compared to Example 2, the introduction of terpyridine structural units further enhances the coordination interactions and spatial support effects between polymer chains, resulting in a more regular pore arrangement and a stable framework structure during phase transformation. This hierarchical porous structure not only helps improve the mechanical strength and structural stability of the material, but also provides more nitrogen-containing coordination sites in the pore wall region, which can effectively promote the uniformity of subsequent metal ion assembly and recombination reactions.

[0091] Depend on Figure 9 It is evident that the terpyridine-polyethersulfone material prepared by this invention possesses a composite pore structure characterized by a dense surface, interconnected channels, and a stable framework, which significantly improves the material's permeability and the adjustability of its interfacial functions, providing an excellent structural basis for constructing multi-coordination networks and realizing multifunctional adsorption and separation applications.

[0092] Figure 10 The nitrogen adsorption-desorption isotherms of Tpy-PES and its metal coordination complex Tpy-PES-Fe are presented. Both samples exhibit typical type IV isotherm characteristics in the relative pressure range of 0.0 to 1.0, indicating that the materials have a certain mesoporous structure.

[0093] In the low-pressure region, P / P0 < 0.2, the adsorption capacity of both increases slightly with increasing pressure, indicating that there is limited microporous adsorption on the sample surface; while in the medium-high pressure region, P / P0 > 0.4, the adsorption capacity increases rapidly, accompanied by a slight hysteresis loop, indicating that the material contains a certain proportion of mesopores or hierarchical pore structures with a wide pore size distribution.

[0094] Based on the specific surface area data, the BET specific surface area of ​​Tpy-PES is 24.7 cm³·g. -1 Slightly higher than Tpy-PES-Fe's 22.8 cm³·g -1 This indicates that after the introduction of iron ions, some pores may be occupied or shielded by coordination structures, resulting in a slight decrease in specific surface area. The coordination interaction between iron ions and tripyridine ligands may lead to a more compact local structure, reducing the accessibility of gas adsorption sites.

[0095] Overall, Tpy-PES and its metal coordination complexes maintained good porous structure characteristics. Although the introduction of iron ions slightly reduced the specific surface area, it did not disrupt the overall pore distribution, providing a favorable structural basis for subsequent studies on metal ion adsorption and catalytic performance.

[0096] Figure 13 Fourier transform infrared (FTIR) spectra of three metal coordination composite materials—Tpy-PES-Fe, Bpy-PES-Zn, and By-PES-Ag—and their ligand-modified films are shown. The spectra of each sample are in the range of 500–1750 cm⁻¹. -1The peaks exhibited typical functional group vibration absorption peaks within the range, reflecting the characteristic absorption of the polyethersulfone backbone structure and its ligand groups.

[0097] At approximately 1600cm -1 At approximately 830–880 cm⁻¹, all samples exhibited a distinct C=C stretching vibration peak νC=C. This peak originates from the characteristic vibrations of the pyridine ring or aromatic ring skeleton, indicating that the pyridine ligands maintain the stability of their aromatic structure after modification. -1 Nearby, both Tpy-PES and Tpy-PES-Fe observed the =CH vibration peak ν=CH, corresponding to the out-of-plane bending vibration of C–H on the aromatic ring.

[0098] Notably, new or enhanced absorption bands appeared in the metal-coordinated samples. For example, the Tpy-PES-Fe and Bpy-PES-Zn samples showed absorption bands in the range of approximately 1050–1150 cm⁻¹. -1 The regions all exhibit distinct absorption peaks, which can be attributed to stretching vibrations of M–O, νCo–O, or νFe–O, indicating effective coordination between the metal ion and the nitrogen or oxygen atoms in the ligand. Furthermore, the slight redshift of the C=C characteristic peak after coordination further confirms the redistribution of electron clouds between the metal and ligands.

[0099] Figure 14 The hemolysis rates of different membrane materials, PES, Tpy-PES, By-PES, and Bpy-PES, are compared to evaluate their blood compatibility. As shown in the figure, the pure polyethersulfone membrane exhibits the highest hemolysis rate, approximately 2.0%, indicating that its surface easily induces erythrocyte rupture and has poor blood compatibility. After modification with pyridine ligands, the hemolysis rates of all three composite membrane materials significantly decreased, demonstrating that the alteration of the surface chemical structure effectively improved the interaction with erythrocytes. Specifically, the hemolysis rates of Tpy-PES and Bpy-PES were approximately 1.1% and 1.0%, respectively, both significantly lower than that of the unmodified PES membrane, indicating that modification with tripyridine (Tpy) and dipyridine (Bpy) groups significantly improves the blood compatibility of the materials. This may be attributed to the introduction of pyridine ligands increasing surface hydrophilicity and reducing non-specific protein adsorption, thereby reducing erythrocyte membrane damage. While the hemolysis rate of By-PES was approximately 1.8%, slightly lower than that of PES, the improvement was limited, indicating that its modified structure has a relatively weak effect on improving blood compatibility.

[0100] Overall, the hemolysis rates of the materials were all well below the 5% threshold of the international safety standard ISO 10993-4, indicating that these membrane materials all possess good blood compatibility. Among them, Tpy-PES and Bpy-PES exhibited the best anti-hemolysis performance, providing experimental evidence for their potential applications in biomedical separation membranes and blood purification.

[0101] Overall, the infrared spectra of all three metal composite films showed successful binding of pyridine ligands to metal ions, with the Tpy-PES-Fe exhibiting the most prominent coordination signal. This indicates that the tripyridine structure forms a more stable metal complex due to the presence of more coordination sites. This result is consistent with UV-Vis absorption and XRD analyses, further verifying that metal ions successfully intercalate into the polyethersulfone matrix via coordination, thereby constructing a stable metal-organic hybrid structure.

[0102] The above description is merely a preferred embodiment of the present invention, and the specific embodiments described above are not intended to limit the present invention. Various modifications and variations can be made within the scope of the technical concept of the present invention. All refinements, modifications, or equivalent substitutions made by those skilled in the art based on the above description are within the scope of protection of the present invention.

Claims

1. A polyethersulfone-based material with blood purification and anticoagulation functions, characterized in that, The structural formula of the polyethersulfone-based material is any one of formulas (1) to (3); Equation (1) Equation (2), Equation (3); Where n is 300–800, M is a soluble metal salt, and R is an anticoagulant.

2. The polyethersulfone-based material with blood purification and anticoagulation functions according to claim 1, characterized in that, The anticoagulant is argatroban or heparin; The soluble metal salt is any one of zinc nitrate, silver hexafluorophosphate, and ferric chloride.

3. A method for preparing a polyethersulfone-based material with blood purification and anticoagulation functions as described in claim 2, characterized in that, Includes the following steps: Using pyridine and polyethersulfone as raw materials, a grafting reaction was carried out in the first reaction solvent system to obtain pyridine-polyethersulfone ligands; Using pyridine-polyethersulfone ligands and soluble metal salts as raw materials, a first coordination reaction was carried out in a second reaction solvent system to obtain metal ligands; Using metal ligands and anticoagulant drugs as raw materials, a second coordination reaction is carried out in a third reaction solvent system to obtain a polyethersulfone-based material with dual functions of blood purification and anticoagulation.

4. The method for preparing the polyethersulfone-based material with blood purification and anticoagulation functions according to claim 3, characterized in that, The mass ratio of the pyridine ligand to the polyethersulfone is 1 to 2:1, the grafting reaction temperature is 25°C to 45°C, and the time is 8 to 22 hours.

5. The method for preparing the polyethersulfone-based material with blood purification and anticoagulation functions according to claim 3, characterized in that, The mass ratio of pyridine-polyethersulfone ligand to soluble metal salt is 1:1 to 3, the temperature of the first coordination reaction is 25℃ to 55℃, and the time is 8h to 20h.

6. The method for preparing the polyethersulfone-based material with blood purification and anticoagulation functions according to claim 3, characterized in that, The mass ratio of the metal ligand to the anticoagulant is 1:4 to 10, and the second coordination reaction takes place at 25℃ to 30℃ for 4 to 8 hours.

7. The method for preparing the polyethersulfone-based material with blood purification and anticoagulation functions according to claim 4, characterized in that, The specific process for obtaining the pyridine-polyethersulfone ligand is as follows: Using acylpyridine as the acylation unit and amino-modified polyethersulfone as the nucleophilic unit, an amidation coupling reaction was carried out under alkaline conditions and an acyl chloride acylation reaction system in an inert gas protection environment to obtain pyridine-polyethersulfone ligands.

8. The method for preparing the polyethersulfone-based material with blood purification and anticoagulation functions according to claim 7, characterized in that, The mass ratio of acylpyridine to amino-modified polyethersulfone is 2–8:1, the temperature of the amide coupling reaction is 25℃–45℃, and the time is 4h–10h. The acylpyridine is any one of acyl monopyridine, acyl dipyridine, or acyl tripyridine. The pH value under alkaline conditions is 8-9.

9. The method for preparing the polyethersulfone-based material with blood purification and anticoagulation functions according to claim 1, characterized in that, The first reaction solvent is dichloromethane, the second reaction solvent is ethanol, and the third reaction solvent is N,N-dimethylformamide.

10. The application of a polyethersulfone-based material with blood purification and anticoagulation functions as described in claim 2 in hemodialysis and blood filtration, characterized in that, It is used to remove blood toxins and regulate anticoagulation.

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