Non-degradable anti-protein adsorption material, and preparation method and application thereof

Abstract

This invention discloses a non-degradable anti-protein adsorbent material, its preparation method, and its application in the field of anti-protein adsorption. The non-degradable anti-protein adsorbent material is a block polymer with a silane coupling agent as a crosslinking site, or a material formed by crosslinking materials including a block polymer. The block polymer is non-degradable, and its molecular chain composition includes hydrophilic polyethylene glycol segments, hydrophobic segments introduced by a hydrophobic monomer, and crosslinking segments introduced by a crosslinking monomer. The hydrophilic polyethylene glycol segments are located between the hydrophobic segments, which are one or more combinations of methacrylate segments and aryl-substituted polyolefin segments. The crosslinking monomer is a silane coupling agent with carbon-carbon double bonds. The preparation method includes: obtaining the block polymer through a controlled / living radical polymerization reaction; or, after obtaining the block polymer according to the above process, further obtaining the non-degradable anti-protein adsorbent material through thermal crosslinking.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials, specifically to a non-degradable anti-protein adsorption material, its preparation method, and its application. Background Technology

[0002] In recent years, the demand for implantable medical devices has been continuously increasing. Cardiovascular stents and orthopedic prostheses have been widely used in clinical practice; cutting-edge products such as biochemical signal sensors and brain-computer interfaces are also constantly being developed and improved. However, when foreign implants enter the human body and come into contact with blood or body fluids, they can trigger a foreign body reaction within a very short time. The adsorption of plasma proteins can induce thrombus formation, leading to a decrease in device efficacy and safety; the collagen fiber capsules formed by the foreign body reaction can not only cause tissue deformation and patient pain, but also affect the sensitivity and lifespan of sensors. In addition, protein adsorption can also cause bacteria to colonize the surface of the implant in the body. Current anti-inflammatory and anticoagulant drugs and antibiotic adjuvant therapy can produce many side effects, bringing other health risks.

[0003] Ultimately, the non-specific adhesion of proteins to material surfaces is a prerequisite for foreign body reactions. Compared to hydrophilic interfaces, proteins are more readily adsorbed onto hydrophobic matrices. Therefore, techniques such as physical adsorption, interfacial gel network construction, layer-by-layer self-assembly (LBL), and surface grafting can be used to modify hydrophobic interfaces with hydrophilic chemical modifiers, relying on hydrophilic molecules to form a hydrated layer to improve the material's antifouling performance. Among these, physical adsorption strategies have poor long-term stability; high-water-content interfacial gel layers applied to blood contact devices pose a risk of platelet damage; LBL is generally not suitable for small-volume substrates or substrates intolerant to aquatic environments, and the impregnation assembly process is time-consuming and labor-intensive, thus limiting its application. In contrast, surface grafting techniques using strongly hydrating molecules such as polyethylene glycol (PEG) and zwitterionic compounds (e.g., phosphocholine) are more mature, and PEG or polyethylene oxide (PEO) molecular brush grafting onto material surfaces to achieve hydrophilic modification is considered the gold standard for antifouling applications. However, the antifouling performance of this PEG molecular brush-based anti-protein adhesion surface is highly dependent on the grafting density and uniformity of PEG. Any minute defects on the material surface can cause the antifouling coating design to fail. To achieve high-density preparation of the PEG molecular brush coating on the material surface, current methods employ "grafting to" and "grafting to self," requiring physical and chemical modifications to the substrate material before preparation, a relatively cumbersome process. Compared to the difficulty in preparing and the ease with which antifouling coatings fail, the exposure of the internal antifouling structure of the bulk material during service can effectively compensate for the damaged antifouling performance at the interface. However, gel materials prepared from polymers with strong hydration capabilities typically have poor mechanical properties due to their high water content, severely limiting their use as functional implants in vivo. In particular, for medical devices requiring long-term implantation, the long-term stability of the antifouling performance of the coating and bulk material in the in vivo environment is crucial. Extending device lifespan and reducing replacement frequency can effectively reduce patient treatment pain and improve patient compliance.

[0004] Therefore, the key technical bottlenecks in preventing protein adhesion in implantable medical devices lie in: 1. Due to the limitations of traditional anti-protein adhesion molecules, there is currently a lack of simple, easy-to-implement, and stable surface coating modification methods; 2. Traditional antifouling hydrophilic polymers have high swelling rates when preparing bulk materials, making it difficult to maintain the initial shape and simultaneously achieve both mechanical properties and antifouling characteristics. In summary, for materials and devices requiring long-term implantation, there is an urgent need to develop a novel, non-degradable antifouling molecule and related implementation technology. This molecule, when used in antifouling coatings, allows for simple and rapid surface modification; as a bulk material, its mechanical strength is adjustable, it has a wide range of applications, and it possesses continuous anti-protein adsorption capabilities in subsequent application scenarios. Summary of the Invention

[0005] To address the aforementioned technical problems and shortcomings in this field, the present invention provides a non-degradable anti-protein adsorption material, its preparation method, and its application.

[0006] The specific technical solution is as follows:

[0007] [1] A non-degradable anti-protein adsorbent material, wherein the non-degradable anti-protein adsorbent material is a block polymer with a silane coupling agent as a crosslinking site or a material formed by crosslinking a material including the block polymer.

[0008] The block polymer is non-degradable, and its molecular chain composition includes polyethylene glycol hydrophilic segments, hydrophobic segments introduced by hydrophobic monomers, and crosslinked segments introduced by crosslinking monomers. The polyethylene glycol hydrophilic segments are located between the hydrophobic segments. The hydrophobic segments include one or more combinations of methacrylate segments and aryl-substituted polyolefin segments. The crosslinking monomer is a silane coupling agent with carbon-carbon double bonds. The crosslinking monomer can be inserted into the hydrophobic segments and / or form crosslinked segments at the ends of the molecular chains during the polymerization process to provide crosslinking sites required for subsequent reactions; that is, the hydrophobic segments may contain and / or not contain crosslinking monomers. Further, the aryl-substituted polyolefin segments can be introduced by aryl-substituted olefins, wherein the olefins can be C1-C4 olefins, such as ethylene and butene. The aryl group can be phenyl, etc. Optionally, the molar ratio of the hydrophobic monomer to the crosslinking monomer is 100:(5-20).

[0009] The number-average molecular weight of the polyethylene glycol hydrophilic segments can be 100–10000 g / mol, and considering the material properties and antifouling performance after synthesis and processing, it is preferably 800–4000 g / mol.

[0010] The mass percentage of the polyethylene glycol hydrophilic segments in the block polymer can be 5% to 50%, preferably 10% to 40%, such as 20% or 30%. This strict molecular structure percentage is mainly due to two factors: 1. The coverage of hydrated PEG chains has a significant impact on the antifouling performance of the coating. If the PEG content is too low, the hydrated layer cannot completely cover the coating surface, and proteins will adhere to non-hydrated areas, leading to coating failure; 2. When the PEG content is too high, due to its strong hydrophilicity, the material absorbs water and swells in an aqueous environment to form a hydrogel or gel-like hydrated coating. During the water absorption and swelling process, the PEG chains lose their specific antifouling molecular structure due to excessive stretching, and its mechanical properties are poor when used as a bulk material.

[0011] The sum of the mass percentages of hydrophobic segments and crosslinked segments in the block polymer can be 50% to 95%, preferably 60% to 90%, such as 70% or 80%.

[0012] In some embodiments, the sum of the mass percentages of the polyethylene glycol hydrophilic segments, hydrophobic segments, and crosslinked segments in the block polymer may be 100%.

[0013] This invention employs controlled / living radical polymerization, where monomers undergo polymerization to obtain block polymers under the action of end-functionalized polyethylene glycol, initiators, catalysts, ligands, and other reagents. Considering the difference in polymerization reactivity between the crosslinking monomer and the olefin monomer used, if they undergo random copolymerization under the reaction conditions, a one-step feeding method can be used; if the olefin monomer tends to self-polymerize, a segmented reaction can be carried out, and after its full reaction, the crosslinking monomer is added to both ends of the existing polymer chain for further polymerization, ultimately obtaining a block polymer with silane coupling agents as crosslinking sites.

[0014] The hydrophobic monomer may include an olefin monomer. In some embodiments, the olefin monomer may include at least one of methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, hexyl methacrylate, octyl methacrylate, lauryl methacrylate, styrene, phenylbutene, etc.

[0015] The crosslinking monomer may include at least one of 3-(isobutenoyloxy)propyltrimethoxysilane, methacryloyloxypropyltriethoxysilane, 3-trimethoxysilane propylene acrylate, allyltrimethylsilane, vinyltris(β-methoxyethoxy)silane, vinyltrimethoxysilane, and A-151 silane coupling agent.

[0016] The precursor of the terminal functionalized polyethylene glycol may include at least one of bihydroxyl-terminated polyethylene glycol, monomethyl ether polyethylene glycol, and n-arm polyethylene glycol, wherein n≥3, and may be treated as a macromolecular initiator or RAFT reagent, depending on the synthesis method.

[0017] The synthesis method of the non-degradable block polymer material of this invention includes controlled radical polymerization routes such as atom transfer radical polymerization (ATRP) and reversible addition-fracture transfer (RAFT), as well as other effective methods for preparing block polymers. Compared with traditional radical polymerization, the key to controlled radical polymerization lies in the dynamic balance between the growing chain radicals and dormant species. The rapid exchange between active and dormant species allows for good control of the polymer molecular weight, molecular weight distribution, and polymer structure in controlled radical polymerization, which is crucial for the accurate preparation and performance of the aforementioned antifouling block polymers. When using ATRP, the dormant species / initiator mainly exists in the form of organohalides RX (X is a halogen atom), and the polymer can participate in the reaction as a macromolecular initiator after halogenation. During the reaction, the dormant species are intermittently activated by the activator Mt. m / L(Mt m The transition metal compound representing the low reduced valence state m acts as a catalyst; L is the ligand) activates it to form the growing free radical R· and the passivating agent X-Mt. m+1 / L(Mt m+1(Representing transition metal compounds in a high oxidation state m+1). R· acts as the active species to initiate polymerization. The passivating agent reacts with R· in the reverse reaction to reform the dormant species and activator. This process reduces the free radical concentration and inhibits the chain termination reaction, exhibiting controlled polymerization. RAFT polymerization is initiated by conventional free radical initiators such as azobisisobutyronitrile in the presence of chain transfer agents (RAFT reagents). Its core is regeneration transfer, and it also possesses strong molecular design capabilities.

[0018] The block polymer can be obtained through controlled / living radical polymerization. The raw materials for the controlled / living radical polymerization may include olefin monomers, crosslinking monomers, and end-functionalized polyethylene glycol. The olefin monomers can be used to polymerize and form hydrophobic segments. The end-functionalized polyethylene glycol (which may act as an initiator in some embodiments) can be used to react and form hydrophilic polyethylene glycol segments. The end groups in the end-functionalized polyethylene glycol can be functionalized as one or more combinations of halogen-containing end groups (e.g., halogens), dithioester end groups, and double-bond-containing end groups. Halogen-containing end groups can be used for ATRP polymerization, and dithioester end groups can be used for RAFT polymerization.

[0019] In some embodiments, the controlled / living radical polymerization reaction may be an atom transfer radical polymerization (ATRP) reaction. Accordingly, the raw materials may also include a catalyst and a ligand. The catalyst may include cuprous halides, such as cuprous chloride, cuprous bromide, etc. The amount of catalyst added may be 1.1 to 3 times the molar amount of functionalized end groups (e.g., halogen-containing end groups) in the terminal-functionalized polyethylene glycol. The ligand is mainly used for solubilizing transition metal salts in organic solvents and adjusting the redox potential of the metal center. The ligand may include at least one of 2,2'-bipyridine, pentamethyldiethylenetriamine, etc. The amount of ligand added may be 2.5 to 7.5 times the molar amount of functionalized end groups (e.g., halogen-containing end groups) in the terminal-functionalized polyethylene glycol. Other synthetic methods may use appropriate initiators and related reagents depending on the specific circumstances.

[0020] To ensure the successful introduction of silane coupling agents into the polymer chain, and considering the influence of monomer reactivity ratio, when preparing the block polymer via controlled / living radical polymerization, the amount of crosslinking monomer added in one step can be 5% to 20% of the molar amount of the olefin monomer in the same batch.

[0021] In this invention, the temperature of the controlled / living free radical polymerization reaction can be 50-75°C, such as 70°C or 100°C, and the time can be 5-20 hours, such as 6 hours or 12 hours.

[0022] In this invention, the controlled / living radical polymerization reaction can be carried out using bulk polymerization, solution polymerization, etc. The selected solvent can be tetrahydrofuran, N,N-dimethylformamide, ethanol, toluene, etc., with ultra-dry reagents being preferred.

[0023] In this invention, the crosslinking temperature of the material can be 45-55°C, for example, 50°C.

[0024] [2] The preparation method of the non-degradable anti-protein adsorption material according to [1] includes:

[0025] Prepare olefin monomers, crosslinking monomers and end-functionalized polyethylene glycol, wherein the olefin monomers are used to polymerize and form hydrophobic segments, and the end-functionalized polyethylene glycol is used to react and form hydrophilic segments of polyethylene glycol.

[0026] The block polymer is obtained by a controlled / living radical polymerization reaction of raw materials including olefin monomers, crosslinking monomers, and end-functionalized polyethylene glycol; or...

[0027] After obtaining the block polymer according to the above process, the non-degradable anti-protein adsorption material is further obtained by thermal crosslinking.

[0028] [3] Application of the non-degradable anti-protein adsorption material according to [1] in the field of anti-protein adsorption. The non-degradable anti-protein adsorption material can be used as a bulk material and / or coating material for anti-protein adsorption. When used as a bulk material, products of specific shapes can be obtained by conventional polymer processing methods such as molding, extrusion, injection molding, casting and 3D printing. Compared with gel materials prepared by hydrophilic polymers, the introduction of hydrophobic segments can reduce their swelling rate in an aqueous environment, the entanglement between hydrophobic chains can enhance the cohesive energy of the polymer material, and the silane coupling molecules at both ends of the polymer can achieve internal cross-linking through heating, ensuring the chemical and mechanical stability of the product. By adjusting the degree of polymerization and mass ratio of hydrophilic and hydrophobic segments, as well as the ratio of cross-linked monomers to olefin monomers, the mechanical strength of the bulk material can be controlled. When used as an anti-protein adsorption coating material, the coating thickness can be 0.01 to 50 micrometers. An exemplary preparation method may include: introducing active groups (such as hydroxyl groups) into the surface to be modified (e.g., through pretreatment methods such as plasma); dissolving the non-degradable anti-protein adsorption material in a solvent (which may include at least one of dichloromethane, anhydrous ethanol, tetrahydrofuran, ethyl acetate, etc.); in some cases, the mass fraction of the non-degradable anti-protein adsorption material in the resulting solution may be 0.1% to 50%; then, uniformly applying the resulting solution (by spin coating, spraying, dipping, etc.) to the surface to be modified, and cross-linking and curing under heat treatment conditions to enhance the stability of the coating while achieving a tight bond with the substrate material, thereby constructing a non-degradable block polymer antifouling coating on the surface to be modified.

[0029] The coating exhibits excellent resistance to protein adsorption. Its underlying mechanism is as follows: the block polymer is composed of hydrophilic PEG segments, hydrophobic segments such as methacrylates, and olefin crosslinking monomers. After coating formation and thermal crosslinking, the polymer forms specific micro / nano structures on the coating surface, maintaining a molecular-level intermingling of hydrophilic and hydrophobic water segments. In an aqueous environment, the hydrophobic segments adhere tightly to the substrate, while the hydrophilic PEG segments extend outwards, stably exposing themselves on the surface. Through hydrogen bonding, they form strong bonds with water molecules, constructing a robust surface hydration layer that hinders the adhesion of proteins, platelets, and bacteria to the coating surface.

[0030] Compared with the prior art, the beneficial effects of this invention are as follows:

[0031] 1. Through optimization, the molecular weight of PEG and its proportion in the overall polymer are strictly limited: the number-average molecular weight of PEG is 800–4000 g / mol, and the mass of PEG is 10%–40% of the total polymer mass. This invention utilizes the unique molecular structure and intrinsic self-assembly behavior of this amphiphilic block polymer to spontaneously form a molecular-level interleaved and uniformly mixed state between hydrophilic and hydrophobic water segments during the construction of the bulk material or the preparation of the polymer coating. In the aqueous environment, the PEG segments extend outward and are in a strongly hydrated state. Furthermore, the silane coupling agent on the hydrophobic polymer segments crosslinks and cures under thermal initiation conditions, stabilizing the material's mechanical properties and strengthening interfacial bonding. Therefore, this antifouling material can possess both excellent bulk mechanical properties and superior antifouling characteristics under simple and easy implementation conditions. Based on the above design, the anti-protein adsorption material prepared by this invention can achieve a protein adsorption capacity less than or equal to that of a purely hydrophilic, tightly packed material with a relatively low PEG content, while ensuring excellent processability and mechanical properties of the bulk material. It should be noted that this invention focuses on limiting the unique molecular structure, the specific molecular weight of PEG, and the proportion of PEG blocks in the overall polymer, rather than the material synthesis method. Any synthetic method that can obtain this molecule, resulting in a final product with a similar molecular structure to the one we protect, is also within the scope of protection of this invention.

[0032] 2. Compared to diblock copolymers based on polyethylene glycol monomethyl ether, the unique triblock amphiphilic molecular structure of this invention strictly limits the polyethylene glycol blocks within the polymer to hydrophobic segments such as methacrylate, exhibiting bi-terminal fixation. In an aqueous environment, the outward extension of the PEG molecular chains better adapts to external compression, reducing protein permeability, thus exhibiting superior anti-protein adsorption properties compared to diblock polymers of the same mass ratio.

[0033] 3. The anti-protein adsorption polymer material obtained by this invention has good processability. The bulk material can be obtained by molding, extrusion, injection molding, casting and 3D printing. The anti-adsorption coating can also be prepared by spin coating, dip coating and spray coating. Therefore, its applicability is far greater than most anti-protein adsorption materials on the market. Attached Figure Description

[0034] Figure 1 The graph shows the effect of the mass ratio of polyethylene glycol blocks in the block polymer on the anti-protein adsorption performance of the material.

[0035] Figure 2 This is a comparison chart showing the anti-protein adsorption performance of the diblock polymer materials in Comparative Example 1 and the triblock polymer materials in Example 2 when applied as a coating.

[0036] Figure 3 A comparison chart showing the antiplatelet adhesion properties of the base material TPU, the coating of Comparative Example 1, and the coating of Example 2;

[0037] Figure 4 This is a comparison chart of the tensile strength between PEGDA and the triblock polymer material of Example 2. Detailed Implementation

[0038] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0039] Unless otherwise specified, the unit for number-average molecular weight is g / mol.

[0040] Example 1

[0041] Preparation of PBMA / SCA-PEG-PBMA / SCA-105 (PBEB105-Si) Non-degradable Antifouling Material and Coating

[0042] 1. Preparation of macromolecular initiators (bi-terminated PEG, Br-PEG-Br):

[0043] 3.63 g of hydroxyl-terminated polyethylene glycol (PEG) with a number-average molecular weight of 1000 was dissolved in 30 mL of dichloromethane (DCM) in a 100 mL round-bottom flask, and a certain amount of anhydrous sodium sulfate was added to bind the water in the system. 3.6 mL of triethylamine (TEA) was added as an acid-binding agent, and 2.7 mL of bromoisobutyryl bromide was added dropwise to the flask under ice-water bath conditions. The reaction was then carried out at room temperature for 12 h. After terminating the reaction, impurities were removed by extraction, and the product Br-PEG-Br was obtained by precipitation with ice-cold diethyl ether.

[0044] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0045] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The polyethylene glycol block in PBEB105-Si accounts for 20% of the total mass. Based on calculations, 140mg of cuprous bromide (CuBr) catalyst, 650mg of Br-PEG-Br, 1.95mL of butyl methacrylate monomer (BMA), and 285μL of anhydrous ethanol solution of 3-(isobutyryloxy)propyltrimethoxysilane (TMSPMA) monomer are added sequentially to the reaction tube. After one freeze-thaw cycle, 400mg of 2,2'-bipyridine (Bpy) ligand is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 70℃ oil bath and reacted continuously for approximately 12 hours. The reaction is then terminated, and post-processing is performed to obtain a triblock polymer (PBEB105-Si) with a number average molecular weight of approximately 5000.

[0046] 3. Preparation of bio-antifouling coating and substrate material:

[0047] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PBEB105-Si was dissolved in tetrahydrofuran (THF) to prepare a polymer solution with a concentration of 10 mg / mL. A uniform coating with a nanometer-thickness was obtained on the substrate by spin coating, and then placed in a 50°C hot oven for 1 h for crosslinking and curing.

[0048] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PBEB105-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0049] Example 2

[0050] Preparation of PBMA / SCA-PEG-PBMA / SCA-110 (PBEB110-Si) Non-degradable Antifouling Material and Coating

[0051] 1. The preparation process of the macromolecular initiator (Br-PEG-Br) is the same as in Example 1.

[0052] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0053] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass percentage of polyethylene glycol blocks in PBEB110-Si is 10%. Based on calculations, 136mg of catalyst CuBr, 612mg of Br-PEG-Br, 4.05mL of BMA monomer, and 605μL of TMSPMA monomer in anhydrous ethanol solution are added sequentially to the reaction tube. After one freeze-thaw cycle, 368mg of ligand Bpy is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 70℃ oil bath and reacted continuously for approximately 12 hours. The reaction is then terminated, and post-processing is performed to obtain a triblock polymer (PBEB110-Si) with a number-average molecular weight of approximately 10,000.

[0054] 3. Preparation of bio-antifouling coating and substrate material:

[0055] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PBEB110-Si was dissolved in THF to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness was obtained on the substrate by spin coating. Then, it was placed in a 50°C hot oven for 1 hour for crosslinking and curing.

[0056] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PBEB110-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0057] Example 3

[0058] Preparation of PBMA / SCA-PEG-PBMA / SCA-120 (PBEB120-Si) Non-degradable Antifouling Material and Coating

[0059] 1. The preparation process of the macromolecular initiator (Br-PEG-Br) is the same as in Example 1.

[0060] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0061] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass percentage of polyethylene glycol blocks in PBEB120-Si is 5%. Based on calculations, 70mg of catalyst CuBr, 307mg of Br-PEG-Br, 4.3mL of BMA monomer, and 640μL of TMSPMA monomer in anhydrous ethanol solution are added sequentially to the reaction tube. After one freeze-thaw cycle, 190mg of ligand Bpy is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 70℃ oil bath and reacted continuously for approximately 12 hours. The reaction is then terminated, and post-processing is performed to obtain a triblock polymer (PBEB120-Si) with a number-average molecular weight of approximately 20,000.

[0062] 3. Preparation of bio-antifouling coating and substrate material:

[0063] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PBEB120-Si was dissolved in THF to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness was obtained on the substrate by spin coating. Then, it was placed in a 50℃ hot oven for 1 hour for crosslinking and curing.

[0064] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PBEB120-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0065] Example 4

[0066] Preparation of PBMA / SCA-PEG-PBMA / SCA-103 (PBEB103-Si) Non-degradable Antifouling Material and Coating

[0067] 1. The preparation process of the macromolecular initiator (Br-PEG-Br) is the same as in Example 1.

[0068] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0069] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass percentage of polyethylene glycol blocks in PBEB103-Si is approximately 30%. Based on calculations, 95mg of catalyst CuBr, 417mg of Br-PEG-Br, 980μL of BMA monomer, and 100μL of TMSPMA monomer in anhydrous ethanol solution are added sequentially to the reaction tube. After one freeze-thaw cycle, 200mg of ligand Bpy is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 70℃ oil bath and reacted continuously for approximately 12 hours. The reaction is then terminated, and post-processing is performed to obtain a triblock polymer (PBEB103-Si) with a number-average molecular weight of approximately 3000.

[0070] 3. Preparation of bio-antifouling coating and substrate material:

[0071] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PBEB103-Si was dissolved in THF to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness was obtained on the substrate by spin coating. Then, it was placed in a 50°C hot oven for 1 hour for crosslinking and curing.

[0072] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PBEB103-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0073] Example 5

[0074] Preparation of PBMA / SCA-PEG-PBMA / SCA-1024 (PBEB1024-Si) Non-degradable Antifouling Material and Coating

[0075] 1. The preparation process of the macromolecular initiator (Br-PEG-Br) is the same as in Example 1.

[0076] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0077] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass percentage of polyethylene glycol blocks in PBEB1024-Si is approximately 40%. Based on calculations, 135mg of catalyst CuBr, 575mg of anhydrous ethanol solution containing Br-PEG-Br, 785μL of BMA monomer, and 156μL of TMSPMA monomer are added sequentially to the reaction tube. After one freeze-thaw cycle, 280mg of ligand Bpy is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 70℃ oil bath and reacted continuously for approximately 12 hours. The reaction is then terminated, and post-processing is performed to obtain a triblock polymer (PBEB1024-Si) with a number-average molecular weight of approximately 2400.

[0078] 3. Preparation of bio-antifouling coating and substrate material:

[0079] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PBEB1024-Si was dissolved in THF to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness was obtained on the substrate by spin coating. Then, it was placed in a 50℃ hot oven for 1 hour for cross-linking and curing.

[0080] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PBEB1024-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0081] Example 6

[0082] Preparation of PBMA / SCA-PEG-PBMA / SCA-102 (PBEB102-Si) Non-degradable Antifouling Material and Coating

[0083] 1. The preparation process of the macromolecular initiator (Br-PEG-Br) is the same as in Example 1.

[0084] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0085] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass percentage of polyethylene glycol blocks in PBEB102-Si is approximately 50%. Based on calculations, 60mg of catalyst CuBr, 255mg of anhydrous ethanol solution containing Br-PEG-Br, 165μL of BMA monomer, and 105μL of TMSPMA monomer are added sequentially to the reaction tube. After one freeze-thaw cycle, 130mg of ligand Bpy is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 70℃ oil bath and reacted continuously for approximately 12 hours. The reaction is then terminated, and post-processing is performed to obtain a triblock polymer (PBEB102-Si) with a number-average molecular weight of approximately 2000.

[0086] 3. Preparation of bio-antifouling coating and substrate material:

[0087] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PBEB102-Si was dissolved in THF to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness was obtained on the substrate by spin coating. Then, it was placed in a 50℃ hot oven for 1 hour for crosslinking and curing.

[0088] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PBEB102-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0089] Figure 1 The results of the anti-protein adsorption performance of the polymer materials of Examples 1 to 6 as coatings are shown, and it can be seen that the polymer material of Example 1 has the best anti-protein adsorption performance.

[0090] Example 7

[0091] Preparation of PS / SCA-PEG-PS / SCA-105 (PSES105-Si) Non-degradable Antifouling Material and Coating

[0092] 1. The preparation process of the macromolecular initiator (Br-PEG-Br) is the same as in Example 1.

[0093] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0094] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100 mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass ratio of polyethylene glycol blocks in PSES105-Si is 20%. According to calculations, 33 mg of catalyst CuBr, 300 mg of Br-PEG-Br, 0.86 mL of styrene monomer (St.), and 130 μL of TMSPMA monomer are added to the reaction tube sequentially. After one freeze-thaw cycle, 98 mg of ligand Bpy is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 100 °C oil bath and reacted continuously for about 6 hours. The reaction is then terminated and post-processed to obtain a triblock polymer (PSES105-Si) with a number average molecular weight of approximately 5000.

[0095] 3. Preparation of bio-antifouling coating and substrate material:

[0096] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PSES105-Si was dissolved in ethyl acetate (EA) to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness was obtained on the substrate by spin coating. Then, it was placed in a 50°C oven for 1 hour for crosslinking and curing.

[0097] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PSES105-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0098] Example 8

[0099] Preparation of PS / SCA-PEG-PS / SCA-110 (PSES110-Si) Non-degradable Antifouling Material and Coating

[0100] 1. The preparation process of the macromolecular initiator (Br-PEG-Br) is the same as in Example 1.

[0101] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0102] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass percentage of polyethylene glycol blocks in PSES110-Si is 10%. Based on calculations, 70mg of catalyst CuBr, 631mg of Br-PEG-Br, 4.1mL of styrene monomer (St.), and 625μL of TMSPMA monomer are added sequentially to the reaction tube. After one freeze-thaw cycle, 210mg of ligand Bpy is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 100℃ oil bath and reacted continuously for approximately 6 hours. The reaction is then terminated, and post-processing is performed to obtain a triblock polymer (PSES110-Si) with a number-average molecular weight of approximately 10,000.

[0103] 3. Preparation of bio-antifouling coating and substrate material:

[0104] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PSES110-Si was dissolved in ethyl acetate (EA) to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness was obtained on the substrate by spin coating. Then, it was placed in a 50°C oven for 1 hour for crosslinking and curing.

[0105] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PSES110-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0106] Example 9

[0107] Preparation of PMMA / SCA-PEG-PMMA / SCA-105 (PMEM105-Si) Non-degradable Antifouling Material and Coating

[0108] 1. The preparation process of the macromolecular initiator (Br-PEG-Br) is the same as in Example 1.

[0109] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0110] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100 mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass ratio of polyethylene glycol blocks in PMEM105-Si is 20%. According to calculations, 66 mg of catalyst CuBr, 600 mg of Br-PEG-Br, 2.17 mL of methyl methacrylate monomer (MMA), and 345 μL of TMSPMA monomer in an ultra-dry 1,4-dioxane solution are added to the reaction tube sequentially. After one freeze-thaw cycle, 200 mg of ligand Bpy is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 100 °C oil bath and reacted continuously for about 6 hours. The reaction is then terminated and post-processed to obtain a triblock polymer (PMEM105-Si) with a number average molecular weight of approximately 5000.

[0111] 3. Preparation of bio-antifouling coating and substrate material:

[0112] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PMEM105-Si was dissolved in THF to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness was obtained on the substrate by spin coating. Then, it was placed in a 50°C hot oven for 1 hour for cross-linking and curing.

[0113] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PMEM105-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0114] Example 10

[0115] Preparation of PMMA / SCA-PEG-PMMA / SCA-110 (PMEM110-Si) Non-degradable Antifouling Material and Coating

[0116] 1. The preparation process of the macromolecular initiator (Br-PEG-Br) is the same as in Example 1.

[0117] 2. Synthesis of triblock polymers with silane coupling agents as crosslinking sites:

[0118] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100 mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass percentage of polyethylene glycol blocks in PMEM110-Si is 10%. According to calculations, 25 mg of catalyst CuBr, 200 mg of Br-PEG-Br, 1.65 mL of methyl methacrylate monomer (MMA), and 256 μL of ultra-dry 1,4-dioxane monomer solution containing TMSPMA monomer are added to the reaction tube sequentially. After one freeze-thaw cycle, 70 mg of ligand Bpy is added, and three more freeze-thaw cycles are performed to ensure thorough deoxygenation. The reaction system is then placed in a 100 °C oil bath and reacted continuously for about 6 hours. The reaction is then terminated and post-processed to obtain a triblock polymer (PMEM110-Si) with a number average molecular weight of approximately 10,000.

[0119] 3. Preparation of bio-antifouling coating and substrate material:

[0120] The substrate to be modified (silicon wafer, glass plate, etc.) was plasma cleaned; the polymer PMEM110-Si was dissolved in THF to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness was obtained on the substrate by spin coating. Then, it was placed in a 50℃ hot oven for 1 h for cross-linking and curing.

[0121] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PMEM110-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0122] Comparative Example 1

[0123] Preparation of PEG-PBMA / SCA-110 (PEB110-Si) non-degradable antifouling material and coating

[0124] 1. Preparation of macromolecular initiators (single-terminal brominated PEG, PEG-Br):

[0125] 2.5 g of polyethylene glycol monomethyl ether with a number average molecular weight of 1000 was dissolved in dichloromethane in a 100 mL round-bottom flask, and a certain amount of anhydrous sodium sulfate was added to bind the water in the system. 2.1 mL of triethylamine (TEA) was added as an acid-binding agent, and 0.95 mL of bromoisobutyryl bromide was added dropwise under stirring in an ice-water bath. The reaction was then carried out at room temperature for 12 h. After terminating the reaction, impurities were removed by extraction, and the product PEG-Br was obtained by precipitation with ice-cold diethyl ether.

[0126] 2. Synthesis of diblock polymers with silane coupling agents as crosslinking sites:

[0127] The reaction must be carried out under anhydrous and oxygen-free conditions. A 100 mL reaction tube is connected to a double-row tube, and the flask is heated with a hot spray gun under vacuum to remove water. After three gas exchanges, argon protection is maintained. The mass percentage of polyethylene glycol blocks in PEB110-Si is 10%. According to calculations, 167 mg of catalyst CuBr, 0.78 g of PEG-Br, 6.7 mL of BMA monomer, and 1 mL of TMSPMA monomer in anhydrous ethanol solution are added to the reaction tube sequentially. After one freeze-thaw operation, 487 mg of ligand Bpy is added, and three more freeze-thaw operations are performed to ensure thorough deoxygenation. The reaction system is then placed in a 70 °C oil bath and reacted continuously for about 12 hours. The reaction is then terminated and post-processed to obtain a diblock polymer (PEB110-Si) with a number average molecular weight of approximately 10,000.

[0128] 3. Preparation of bio-antifouling coating:

[0129] The substrate to be modified (silicon wafer, glass plate, etc.) is plasma cleaned; the polymer PEB110-Si is dissolved in THF to prepare a polymer solution with a concentration of 10 mg / mL, and a uniform coating with a nanometer thickness is obtained on the substrate by spin coating. Then, it is placed in a hot oven at 50°C for 1 h for crosslinking and curing.

[0130] For the preparation of antifouling body material, taking the casting method as an example: take a mold of appropriate size (such as a tetrafluoroethylene mold), dissolve the polymer PEB110-Si in THF to prepare a 400mg / mL polymer concentrated solution, take an appropriate amount of polymer solution to fill the mold, evaporate the solvent under natural conditions, and then place it in a 50℃ hot oven for 1h for cross-linking and curing.

[0131] Figure 2 The anti-protein adsorption properties of the diblock polymer materials of Comparative Example 1 and the triblock polymer materials of Example 2, applied as coatings, are shown. It can be seen that the polymer material of Example 2 has superior anti-protein adsorption properties.

[0132] The TPU substrate to be modified was subjected to plasma cleaning. The polymer from Comparative Example 1 or Example 2 was dissolved in THF to prepare a polymer solution concentration of 10 mg / mL. A uniform coating with a nanometer-thickness was obtained by spin coating onto the substrate. The coating was then placed in a 50°C oven for 1 hour for crosslinking and curing, yielding the coatings for Comparative Example 1 and Example 2, respectively. The antiplatelet adhesion performance was then tested using the TPU substrate as a control. The results are shown in [link to results]. Figure 3 As can be seen, the polymer material in Example 2 has superior anti-platelet adhesion properties.

[0133] Poly(ethylene glycol) diacrylate with a number average molecular weight of 10,000 and photoinitiator I2959 were dissolved in deionized water to prepare a polymer solution with a concentration of 400 mg / mL. The solution was poured into a mold and polymerized under ultraviolet light to form a PEGDA gel material. Figure 4 The tensile strength of the PEGDA gel material and the triblock polymer material of Example 2 are shown. It can be seen that the polymer material of Example 2 has better tensile properties.

[0134] Furthermore, it should be understood that after reading the above description of the present invention, those skilled in the art can make various alterations or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A non-degradable anti-protein adsorption material, characterized in that, The non-degradable anti-protein adsorption material is a block polymer with a silane coupling agent as a crosslinking site or a material formed by crosslinking a material including the block polymer. The block polymer is non-degradable, and its molecular chain composition includes polyethylene glycol hydrophilic segments, hydrophobic segments introduced by hydrophobic monomers, and crosslinked segments introduced by crosslinking monomers. The polyethylene glycol hydrophilic segments are located between the hydrophobic segments, which include one or more combinations of methacrylate segments and aryl-substituted polyolefin segments. The crosslinking monomer is a silane coupling agent with carbon-carbon double bonds. The molar ratio of the hydrophobic monomer to the crosslinking monomer is 100:(5~20). The hydrophobic monomer includes olefin monomers, which include... The crosslinking monomer comprises at least one of methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, hexyl methacrylate, octyl methacrylate, lauryl methacrylate, styrene, and phenylbutene; the crosslinking monomer comprises at least one of 3-(isobutenoyloxy)propyltrimethoxysilane, methacryloxypropyltriethoxysilane, propyl 3-trimethoxysilane acrylate, allyltrimethylsilane, vinyltris(β-methoxyethoxy)silane, vinyltrimethoxysilane, and A-151 silane coupling agent. The number-average molecular weight of the polyethylene glycol hydrophilic segments is 100~10000 g / mol; The block polymer contains 10% to 40% by mass of polyethylene glycol hydrophilic segments.

2. The non-degradable anti-protein adsorption material according to claim 1, characterized in that, The number-average molecular weight of the polyethylene glycol hydrophilic segments is 800~4000 g / mol.

3. The non-degradable anti-protein adsorption material according to claim 1, characterized in that, The block polymer contains 50% to 95% by mass of hydrophobic segments and crosslinked segments. In the block polymer, the total mass percentage of the polyethylene glycol hydrophilic segments, hydrophobic segments, and crosslinked segments is 100%.

4. The non-degradable anti-protein adsorption material according to claim 3, characterized in that, The block polymer contains 60% to 90% hydrophobic segments and cross-linked segments by mass.

5. The non-degradable anti-protein adsorption material according to claim 1, characterized in that, The block polymer is obtained through a controlled / living radical polymerization reaction, which is an atom transfer radical polymerization reaction. The raw material composition of the controlled / living free radical polymerization reaction includes olefin monomers, crosslinking monomers and end-functionalized polyethylene glycol, wherein the olefin monomers are used to polymerize and form hydrophobic segments, and the end-functionalized polyethylene glycol is used to react and form polyethylene glycol hydrophilic segments. The raw materials also include catalysts and ligands; The catalyst includes cuprous halides; The amount of catalyst added is 1.1 to 3 times the molar amount of functionalized end groups in the terminal-functionalized polyethylene glycol; The ligand includes at least one of 2,2'-bipyridine and pentamethyldiethylenetriamine; The amount of ligand added is 2.5 to 7.5 times the molar amount of functionalized end groups in the terminal-functionalized polyethylene glycol.

6. The non-degradable anti-protein adsorption material according to claim 5, characterized in that, When preparing the block polymer via controlled / living radical polymerization, the amount of crosslinking monomer added in the one-step feeding is 5% to 20% of the molar amount of the olefin monomer in the same batch.

7. The non-degradable anti-protein adsorption material according to claim 5, characterized in that, The controlled / living radical polymerization reaction is carried out at a temperature of 50~75 ℃ for 5~20 hours.

8. The non-degradable anti-protein adsorption material according to claim 1, characterized in that, The cross-linking temperature of the material is 45~55℃.

9. The method for preparing the non-degradable anti-protein adsorption material according to any one of claims 1 to 8, characterized in that, include: Prepare olefin monomers, crosslinking monomers and end-functionalized polyethylene glycol, wherein the olefin monomers are used to polymerize and form hydrophobic segments, and the end-functionalized polyethylene glycol is used to react and form hydrophilic segments of polyethylene glycol. The block polymer is obtained by a controlled / living radical polymerization reaction of raw materials including olefin monomers, crosslinking monomers, and end-functionalized polyethylene glycol; or... After obtaining the block polymer according to the above process, the non-degradable anti-protein adsorption material is further obtained by thermal crosslinking.

10. The application of the non-degradable anti-protein adsorption material according to any one of claims 1 to 8 in the field of anti-protein adsorption.

11. The application according to claim 10, characterized in that, The non-degradable anti-protein adsorption material is used as a bulk material and / or coating material for anti-protein adsorption.

Images