A high-molecular functional coating material, a high-molecular functional coating, and a preparation method and application thereof

Abstract

The application discloses a kind of polymer functional coating material, polymer functional coating and its preparation method and application.The polymer functional coating material has the structure as follows:Wherein, R includes any one or two or more combinations of group containing sulfide structure, group containing sulfonium ion structure, group containing sulfoxide structure, group containing sulfone structure, group containing zwitterionic structure, group containing oligoethylene glycol structure;N is selected from any integer between 1-200;X, y represent copolymerization unit molar ratio, x+y=1, 0≤x<1, 0<y≤1.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of high polymer coating and biomedical materials, and particularly relates to a high polymer functional coating material, a high polymer functional coating and a preparation method and application thereof. BACKGROUND

[0002] The application of high polymer functional coating technology in the field of medical materials is one of the important research directions of biomedical engineering in recent decades. With the aging of the population and the rising prevalence of chronic diseases, the demand for medical devices and implants is increasing. In the field of cardiovascular, thrombosis is one of the main risks that threaten the safety of patients. Medical devices such as artificial heart valves, vascular stents and extracorporeal circulation equipment that come into direct contact with blood urgently need surface treatment technology with persistent anticoagulant properties. Hospital infection control has always been a major problem in clinical work. According to statistics, millions of patients are affected by medical-related infections every year, which not only prolongs the hospitalization time and increases the medical expenses, but also can lead to serious complications and even death. In addition, the biofilm formed after bacterial infection is a complex structure formed by the attachment and growth of microorganisms on the surface of implants, which is one of the important reasons for implant infection and loss of function. Therefore, it is urgent to develop medical device surface treatment technology with persistent antibacterial properties. In the key medical fields of organ transplantation and biosensors, it is a core element to effectively reduce the rejection reaction of the body to foreign objects and significantly prolong the actual service life of the implant, which is the key to improving the treatment effect. In view of this, the requirement for biocompatibility in these fields is higher than that of general medical equipment.

[0003] In the face of these clinical challenges, high polymer functional coating technology has emerged and made significant progress in recent decades. Whether in the field of in vivo implants, in vitro diagnosis and treatment equipment, or in the field of wound dressings and skin repair, high polymer functional coating has provided important support and innovative solutions for the development of biomedical technology and the improvement of clinical treatment effect. This technology forms a thin film with specific functions on the surface of medical materials, which significantly improves the biological properties of the surface while retaining the excellent mechanical properties of the substrate. However, the existing technology usually covers a high polymer adhesion layer and then coats a functional coating to construct a high polymer functional coating. The traditional multi-step coating method requires complex pretreatment and intermediate layer coating of the substrate, which is tedious. Due to the multi-step coating, the adhesion molecules and functional molecules in the coating have poor combination, which further leads to poor uniformity of the coating on the surface of materials with more complex shapes, and potential problems such as local failure, uneven wear or poor biocompatibility due to local performance differences, thereby affecting the performance of the coating. SUMMARY

[0004] The present application aims to provide a polymer functional coating material, a polymer functional coating, and a preparation method and application thereof, so as to overcome the deficiencies in the prior art.

[0005] To achieve the aforementioned objects, the present application adopts the technical solutions comprising:

[0006] One aspect of the present application provides a polymer functional coating material, which has a structure as shown in formula (I):

[0007]

[0008] wherein R includes any one of a group containing a sulfide structure, a group containing a sulfonium ion structure, a group containing a sulfoxide structure, a group containing a sulfone structure, a group containing a zwitterion structure, a group containing an oligoethylene glycol structure, or a combination of two or more thereof; n is any integer selected from 1-200; x, y represent the molar ratio of copolymerization units, x+y=1, 0≤x<1, 0<y≤1.

[0009] Another aspect of the present application provides a preparation method of a polymer functional coating material, which comprises: mixing a chain transfer agent having a catechol and / or catechol derivative structure with a functional monomer, and performing a reversible addition-fragmentation chain transfer polymerization reaction to obtain the polymer functional coating material.

[0010] Another aspect of the present application also provides a polymer functional coating material prepared by the aforementioned preparation method.

[0011] Another aspect of the present application also provides a polymer functional coating, which is obtained by applying the aforementioned polymer functional coating material to the surface of a substrate; the thickness of the coating is 100-2000 nm.

[0012] Another aspect of the present application also provides a preparation method of the aforementioned polymer functional coating, which comprises: performing a hydroxylated hydrophilic modification treatment on the surface of a substrate, and then applying the polymer functional coating material to the surface of the substrate in a buffer system to obtain the polymer functional coating.

[0013] Another aspect of the present application also provides the application of the aforementioned polymer functional coating material or the aforementioned polymer functional coating in the field of medical material protection.

[0014] Compared with the prior art, the technical solutions of the present application have at least the following advantages:

[0015] The high-molecular functional coating material provided by the application has a chemical structure inspired by mussel adhesion, and coating coating can be completed in one step by immersing the synthesized high-molecular functional coating material and a medical substrate into a buffer solution, and coating can be smoothly performed on the surfaces of substrates made of various materials; the catechol and derivative structure protected by a TBS group in the molecular structure can effectively avoid oxidation and self-polymerization of catechol and its derivatives; in particular, the protected catechol and its derivatives are introduced into a reversible addition-fragmentation chain transfer agent to synthesize a polymer with a clear main chain structure, and the monomer has good compatibility and can be polymerized with various functional monomers, and in actual application, the cumbersome steps involved in coating construction can be greatly reduced; on the surfaces of metal materials and some special non-metal materials, the high-molecular coating material of the application can effectively form a stable coating, thereby providing a more simple, efficient and widely applicable method for preparing a uniform coating. BRIEF DESCRIPTION OF DRAWINGS

[0016] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings in the following description are only some embodiments described in the application, and for those skilled in the art, other drawings can also be obtained without creative labor on the basis of these drawings.

[0017] Figure 1a The nuclear magnetic hydrogen spectrum of the reversible addition-fragmentation chain transfer agent molecule with catechol and its derivative structure in a typical embodiment of the application;

[0018] Figure 1b The nuclear magnetic carbon spectrum of the reversible addition-fragmentation chain transfer agent molecule with catechol and its derivative structure in a typical embodiment of the application;

[0019] Figure 1c The mass spectrum characterization diagram of the reversible addition-fragmentation chain transfer agent molecule with catechol and its derivative structure in a typical embodiment of the application;

[0020] Figure 2 The nuclear magnetic hydrogen spectrum of the monomer molecule with catechol and its derivative structure in a typical embodiment of the application;

[0021] Figure 3a The nuclear magnetic hydrogen spectrum of the hydrophobic high-molecular coating material molecule in Example 1 of the application;

[0022] Figure 3b The GPC characterization diagram of the hydrophobic high-molecular coating material molecule in Example 1 of the application;

[0023] Figure 4aThe nuclear magnetic hydrogen spectrum of the molecule of the antibacterial high-molecular coating material containing sulfonium ion in Example 1 of the present application;

[0024] Figure 4b The GPC characterization graph of the molecule of the high-molecular coating material containing sulfone in Example 4 of the present application;

[0025] Figure 5a The nuclear magnetic hydrogen spectrum of the molecule of the hydrophilic high-molecular coating material in Example 2 of the present application;

[0026] Figure 5b The GPC characterization graph of the molecule of the hydrophilic high-molecular coating material in Example 2 of the present application;

[0027] Figure 6a The nuclear magnetic hydrogen spectrum of the molecule of the hydrophilic high-molecular coating material with a polymerization degree of 33 in Example 3 of the present application;

[0028] Figure 6b The nuclear magnetic hydrogen spectrum of the molecule of the hydrophilic high-molecular coating material with a polymerization degree of 70 in Example 3 of the present application;

[0029] Figure 6c The nuclear magnetic hydrogen spectrum of the molecule of the hydrophilic high-molecular coating material with a polymerization degree of 101 in Example 3 of the present application;

[0030] Figure 6d The nuclear magnetic hydrogen spectrum of the molecule of the hydrophilic high-molecular coating material with a polymerization degree of 195 in Example 3 of the present application;

[0031] Figure 6e The GPC characterization graph of the molecule of the hydrophilic high-molecular coating material with different polymerization degrees in Example 3 of the present application;

[0032] Figure 7 The nuclear magnetic hydrogen spectrum of the molecule of the high-molecular coating material containing sulfone in Example 4 of the present application;

[0033] Figure 8 The nuclear magnetic hydrogen spectrum of the molecule of the zwitterionic high-molecular coating material in Example 5 of the present application;

[0034] Figure 9 The nuclear magnetic hydrogen spectrum of the molecule of the oligomeric ethylene glycol high-molecular coating material in Example 6 of the present application;

[0035] Figure 10 The X-ray photoelectron spectrum and the element content table of the high-molecular coating constructed by the hydrophilic high-molecular coating material in Example 2 in Example 11 of the present application;

[0036] Figure 11 The platelet adhesion experiment result of the high-molecular coating constructed by the hydrophilic high-molecular coating material in Example 2 in Example 11 of the present application;

[0037] Figure 12 PAOl bacterial adhesion test results for the polymer coating constructed in Example 11 of the present application with the hydrophilic polymer coating material in Example 2;

[0038] Figure 13 Laser confocal microscope results for the E. coli adhesion test of the polymer coating constructed in Example 11 of the present application with the hydrophilic polymer coating material in Example 2;

[0039] Figure 14 Schematic diagram of the polymer coating prepared in a typical embodiment of the present application against bacterial adhesion. DETAILED DESCRIPTION

[0040] The present application will be more fully understood by reading the following detailed description together with the accompanying drawings. It is noted that, as the application herein disclosed is one made by way of example only, the specific embodiments disclosed are not to be construed in a limiting sense but are merely given as representative of the generic application. The particular features of the application disclosed herein are presented solely for purposes of illustration and not limitation.

[0041] As one aspect of the technical solution of the present application, it relates to a polymer functional coating material having a structure as shown in formula (I):

[0042]

[0043] wherein R includes but is not limited to any one of a group containing a sulfide structure, a group containing a sulfonium ion structure, a group containing a sulfoxide structure, a group containing a sulfone structure, a group containing a zwitterion structure, a group containing an oligoethylene glycol structure, or a combination of two or more thereof; n is selected from any integer between 1 and 200; x, y represent the molar ratio of copolymerization units, x+y=1, 0≤x<1, 0<y≤1.

[0044] As another aspect of the technical solution of the present application, it relates to a preparation method of a polymer functional coating material, comprising: mixing a chain transfer agent having a catechol and / or catechol derivative structure with a functional monomer, and performing a reversible addition-fragmentation chain transfer polymerization reaction to obtain the polymer functional coating material.

[0045] It should be noted that although in the prior art, monomers containing catechol structures and monomers containing zwitterionic groups can be polymerized, monomers synthesized from catechol derivatives do not have good compatibility with all functional monomers. The present application introduces catechol and its derivatives into a reversible addition-fragmentation chain transfer agent (RAFT agent) to synthesize polymers with a clear main chain structure. This feature brings significant compatibility advantages to coating technology. The reversible addition-fragmentation chain transfer agent of the present application can provide wide monomer compatibility and can be further polymerized with various functional monomers to prepare high-molecular functional coating materials that are stable and have certain functions in combination with substrates.

[0046] In some embodiments, the preparation method comprises: mixing a chain transfer agent having a catechol and / or catechol derivative structure, a monomer having a catechol and / or catechol derivative structure, and a functional monomer, and performing a reversible addition-fragmentation chain transfer polymerization reaction to obtain a high-molecular functional coating material.

[0047] In the reaction of the present application, monomers with catechol and / or catechol derivative structures can also not be added, and high-molecular functional coating materials can also be obtained. Adding them can increase the coating rate and stability after coating, and not adding them does not affect their intrinsic properties.

[0048] In some preferred embodiments, the functional monomer includes, but is not limited to, any one or a combination of two or more of a monomer containing a sulfide structure, a monomer containing a sulfonium ion structure, a monomer containing a sulfoxide structure, a monomer containing a sulfone structure, a monomer containing a zwitterionic structure, and a monomer containing an oligoethylene glycol structure.

[0049] The present application provides compatibility for coating different material surfaces through mussel-inspired high-molecular structures. A high-molecular coating material with catechol and its derivative structures is prepared through reversible addition-fragmentation chain transfer polymerization. Functional monomers are used as choices under specific requirements to give the coating functions in different scenarios. For example, a sulfide structure can give the coating hydrophobic properties, a sulfonium ion structure can give the coating antibacterial properties due to the bactericidal effect of cations, a sulfoxide structure can give the coating hydrophilic properties, a sulfone structure can resist protein adhesion, a zwitterionic structure can give the coating extensive antifouling properties, and an oligoethylene glycol structure can give the coating both good biocompatibility and certain hydrophilicity.

[0050] Further, the monomer containing a sulfide structure has a structure as shown in formula (1):

[0051]

[0052] Further, the monomer containing a sulfonium ion structure has a structure as shown in formula (2):

[0053]

[0054] Further, the monomer containing a sulfoxide structure has a structure as shown in formula (3):

[0055]

[0056] Further, the monomer containing a sulfone structure has a structure as shown in formula (4) or formula (5):

[0057]

[0058] Further, the monomer containing a zwitterion structure has a structure as shown in at least any one of formula (6) to formula (11):

[0059]

[0060] Further, the monomer containing an oligoethylene glycol structure has a structure as shown in formula (12):

[0061]

[0062] n in formula (12) is selected from any integer between 1 to 50.

[0063] In some preferred embodiments, the molar ratio of the chain transfer agent having a catechol and / or catechol derivative structure, the monomer having a catechol and / or catechol derivative structure, and the functional monomer is (1-5):(1-30):(10-200).

[0064] In some preferred embodiments, the polymerization temperature of the reversible addition-fragmentation chain transfer polymerization is 70-80°C, and the polymerization time is 6-12h.

[0065] In some preferred embodiments, the chain transfer agent having a catechol and / or catechol derivative structure has a structure as shown in formula (II):

[0066]

[0067] In some preferred embodiments, the monomer having a catechol and / or catechol derivative structure has a structure as shown in at least any one of formula (III) or formula (IV):

[0068]

[0069] The catechol and / or catechol derivative structure protected by TBS in the present application is beneficial to the synthesis of the polymer (phenolic hydroxyl group polymerization inhibition), can prevent the catechol and its derivatives from self-polymerization to affect the coating performance of the coating, and can make the coating material be long-term preserved, and the silane protection can be removed to ensure the effectiveness when used.

[0070] In some embodiments, the preparation method comprises: mixing a chain transfer agent having a catechol and / or catechol derivative structure, a monomer having a catechol and / or catechol derivative structure, a functional monomer, a polymerization initiator and a solvent to form a mixed reaction system, and performing a reversible addition-fragmentation chain transfer polymerization reaction to prepare a high-molecular functional coating material.

[0071] In some preferred embodiments, the polymerization initiator comprises, but is not limited to, azobisisobutyronitrile (AIBN).

[0072] In some preferred embodiments, the molar ratio of the polymerization initiator to the chain transfer agent having a catechol and / or catechol derivative structure is 0.1-0.5:1-10.

[0073] In some preferred embodiments, the solvent comprises, but is not limited to, dimethyl sulfoxide (DMSO).

[0074] In some preferred embodiments, the mass-to-volume ratio of the mixed reaction system to the solvent is (10-1200) mg:(100-1200) μL.

[0075] As another aspect of the technical solution of the present application, it also relates to a high-molecular functional coating material prepared by the aforementioned preparation method.

[0076] As another aspect of the technical solution of the present application, it relates to a high-molecular functional coating obtained by applying the aforementioned high-molecular functional coating material to the surface of a substrate; and a coating with a thickness of 100-2000 nm can be constructed according to the coating dip-coating time.

[0077] As another aspect of the technical solution of the present application, it also relates to a preparation method of the aforementioned high-molecular functional coating, which comprises: performing a hydroxylated hydrophilic modification treatment on the surface of a substrate, and then applying the high-molecular functional coating material to the surface of the substrate in a buffer system to prepare the high-molecular functional coating.

[0078] In some embodiments, the preparation method specifically comprises:

[0079] (1) The substrate (e.g., medical material) is subjected to hydroxylated hydrophilic modification treatment on the surface by an oxygen plasma cleaning machine to make the substrate surface rich in hydroxyl groups; the oxygen plasma cleaning first performs surface hydroxylated modification on the material base, which can improve the coating efficiency and coating stability;

[0080] (2) The high-molecular functional coating material is dissolved in a buffer system to obtain a mixed solution, and the substrate is immersed in the mixed solution, so as to construct the high-molecular functional coating on the surface of the medical material in one step.

[0081] The one-step coating process of the present application greatly simplifies the coating preparation process. The one-step coating process is achieved by the catechol derivative structure contained in the high-molecular functional coating. Compared with the traditional multi-step coating method, there is no need for complex pretreatment and intermediate layer coating, and only one step is needed to uniformly form a coating on the surface of the biomaterial. This not only improves the production efficiency, saves time and labor cost, but also reduces the errors and quality instability factors that may be introduced by multi-step operation. In large-scale production, this high efficiency and convenience advantage is particularly prominent, which can quickly meet the market demand for medical material coating.

[0082] Further, through the precise control of the one-step coating process, the coating can be uniformly distributed on the surface of the biomaterial. Whether the shape of the material is regular or complex, such as an implant with small pores or curved structure, uniform coating coverage can be achieved. This uniformity is crucial for the performance of the coating, which ensures that the biomaterial can obtain the same protection and functional improvement at all parts, avoiding potential problems caused by local performance differences, such as local corrosion, uneven wear or poor biocompatibility, thereby improving the overall quality and reliability of the product.

[0083] In some embodiments, the substrate includes but is not limited to any one or a combination of two or more of polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene, expanded polytetrafluoroethylene, polylactic acid, polycarbonate, polyurethane, polystyrene, polysulfone, polyethersulfone, polyacrylonitrile, polymethacrylate, latex, silicone rubber, glass, ceramic, stainless steel, titanium alloy, nickel-titanium alloy.

[0084] In some embodiments, the hydroxylated hydrophilic modification treatment includes: placing the substrate in a vacuum plasma cleaning machine, and subjecting the substrate to oxygen plasma treatment under the conditions of a radio frequency power of 100-300 W and a gas flow rate of 100-500 mL / min to obtain a hydrophilic surface rich in hydroxyl groups.

[0085] In some embodiments, the buffer system includes but is not limited to a tris(hydroxymethyl)aminomethane solution buffer system.

[0086] In some preferred embodiments, the concentration of tris(hydroxymethyl)aminomethane in the buffer system is 10-20 mM.

[0087] In some embodiments, the pH value of the buffer system is 8-9.

[0088] As another aspect of the technical solution of the present application, it also relates to the application of the aforementioned high-molecular functional coating material or the aforementioned high-molecular functional coating in the field of medical material protection.

[0089] In summary, the present application provides a one-step coating high-molecular functional coating, which is mainly composed of two components, one is a polymer monomer that provides functionality to the coating, and the other is catechol and its derivatives that realize one-step coating process. According to the specific application requirements, the corresponding functional monomers are selected, and the reversible addition-fragmentation chain transfer agent is combined with the catechol derivative monomer to perform reversible addition-fragmentation chain transfer polymerization, and the corresponding high-molecular coating material is synthesized. After a simple deprotection procedure, the coating construction can be completed in one step in a simple biological buffer system. This technology provides a widely functional tool library for material surface functionalization, which can be customized and synthesized according to different medical needs to achieve precise functionalization. At the same time, compared with existing processes, this technology significantly simplifies the coating preparation process, and shows excellent compatibility and wide applicability to various substrate materials.

[0090] The high-molecular functional coating material with one-step coating function provided by the present application can be customized to different functional high-molecular coatings according to the functional requirements for different application scenarios, and a high-molecular film with specific functions is formed on the surface of medical materials, thereby endowing medical devices or implants with new properties such as antibacterial, anticoagulant, biocompatibility, etc.

[0091] The high-molecular functional coating material with one-step coating function provided by the present application effectively solves many pain points in the biomedical industry through its unique advantages and expandable functionality, as well as innovative high-molecular design, controllable synthesis and process, has broad application prospects and great market value, and will make important contributions to promoting the progress of biomedical technology and improving the quality of life of patients.

[0092] The present application will be further described by way of examples below, but the present application is not limited to the scope of the examples. The reagents and raw materials used in the following examples are commercially available, and the test methods not specified in the following examples are usually carried out under conventional conditions or according to the conditions recommended by the manufacturers.

[0093] For example, the reversible addition-fragmentation chain transfer agent with catechol and its derivative structure used in the embodiments of the present application can be synthesized by the following steps:

[0094]

[0095] The specific preparation method is: 0.69 g of CTA is dissolved in 20 mL of DCM and stirred to dissolve, 0.81 g of EDC is added to activate the carboxyl group for 30 min, 1 g of silane-protected catechol and its derivatives (DA-TBS) is dissolved in 10 mL of DCM and added to the flask, 0.06 g of DMAP is added to catalyze the reaction, after overnight reaction, the solvent is removed under reduced pressure, and then the yellow product CTA-DA-TBS (1.11 g, yield: 67.3%) is further purified by column chromatography (PE:EA=10:1). The structure and purity are verified by nuclear magnetic hydrogen spectrum and carbon spectrum and mass spectrum, and the results are shown in Figure 1a 、 Figure 1b and Figure 1c .

[0096] For example, the monomer with the structure of catechol and its derivatives used in the embodiment of the application can be synthesized by the following steps:

[0097]

[0098] The specific preparation method is: 3 g of TBS-protected catechol and its derivatives and 30 mL of DCM are added to a flask and placed in an ice bath, 0.79 g of triethylamine is added to the flask, and then 0.72 g of acryloyl chloride is added dropwise, the reaction is completed after 3 h, the organic phase is separated after washing with saturated aqueous sodium bicarbonate solution, and the organic phase is dried with anhydrous sodium sulfate, the solvent is removed under reduced pressure, and then the light brown solid product (3.15 g, yield: 92%) is further purified by column chromatography (PE:EA=1:1). The structure and purity are verified by nuclear magnetic hydrogen spectrum, and the results are shown in Figure 2 .

[0099] Example 1

[0100] The embodiment provides a preparation method of a one-step-coatable hydrophobic polymer coating material (containing a sulfide structure). The reaction and synthesis process is as follows:

[0101]

[0102] Specific steps are: 2-(methylthio) ethyl acrylate (298 mg, 100 equivalents), AIBN (1.1 mg, 0.2 equivalents) and CTA-DA-TBS (20 mg, 1 equivalent) are dissolved in 0.3 mL of DMSO and added to a polymerization reaction tube, which is degassed by repeating the freeze-thaw cycle three times and sealed under vacuum. The polymerization reaction solution is reacted at 70°C for 8 hours, and the polymerization reaction is quenched with liquid nitrogen, and the reaction tube is opened. The solution is precipitated into an excess of ethyl ether solution (40 mL). The above dissolution-precipitation cycle is repeated three times, and then the filter cake is collected by filtration and dried in a vacuum oven at room temperature overnight to obtain a yellow product. The structure and molecular weight distribution are characterized by hydrogen nuclear magnetic resonance spectrum and GPC, and the results are shown in Figure 3a 、 Figure 3b When constructing the coating, the hydrophobic polymer coating material is placed in a 1 mM p-toluenesulfonic acid DCM solution to remove the silane protecting group, and then used after removing the solvent under reduced pressure.

[0103] In addition, the obtained yellow product can be subjected to methylation reaction to obtain a sulfur onium ion-containing antibacterial polymer coating material, and the reaction synthesis process is as follows:

[0104]

[0105] Specific steps are: the above obtained yellow product (200 mg, 1 equivalent) is dissolved in 2 mL of DMF, iodomethane (20 mg, 10 equivalents) is added, and the reaction is carried out at 90°C for 8 hours. After removing the organic solvent by dialysis, the white powder product is obtained by freeze-drying, and the structure and molecular weight distribution are characterized by hydrogen spectrum and GPC, and the results are shown in Figure 4a 、 Figure 4b

[0106] Example 2

[0107] This example provides a preparation method of a one-step coatable hydrophilic polymer coating material (containing a sulfoxide structure), and the reaction synthesis process is as follows:

[0108]

[0109] ​Specific steps are: 2-(methylsulfonyl) ethyl acrylate (517 mg, 100 equivalents), AIBN (1.1 mg, 0.2 equivalents) and CTA-DA-TBS (20 mg, 1 equivalent) are dissolved in 0.3 mL of DMSO and added to the polymerization reaction tube, the reaction tube is degassed by repeating the freeze-degassing-thaw cycle three times, and sealed under vacuum. The polymer reaction solution is reacted at 70°C for 8 hours, the polymerization reaction is quenched with liquid nitrogen, and the reaction tube is opened. The solution is precipitated into an excess of ethyl ether solution (40 mL). The above dissolution-precipitation cycle is repeated three times, then the filter cake is collected by filtration, and dried in a vacuum oven at room temperature overnight to obtain a yellow product. Its structure and molecular weight distribution are characterized by nuclear magnetic resonance hydrogen spectrum and GPC, and the results are shown in Figure 5a 、 Figure 5b When constructing the coating, the hydrophilic polymer coating material is placed in a 1 mM p-toluenesulfonic acid DCM solution to remove the silane protecting group, and then used after removing the solvent under reduced pressure.

[0110] Example 3

[0111] The present embodiment provides a method for preparing a one-step coatable hydrophilic polymer coating material with different molecular weights.

[0112] According to the preparation method in Example 2, by adjusting the equivalent ratio between the polymerization monomer 2-(methylsulfonyl) ethyl acrylate and the chain transfer agent CTA-DA-TBS, polymers with different polymerization degrees (33, 70, 101, and 195, respectively) are synthesized.

[0113] Specific steps are: 2-(methylsulfonyl) ethyl acrylate (517 mg, 100 equivalents), AIBN (1.1 mg, 0.2 equivalents) and CTA-DA-TBS (20 mg, 1 equivalent) are dissolved in 0.3 mL of DMSO and added to the polymerization reaction tube, the reaction tube is degassed by repeating the freeze-degassing-thaw cycle three times, and sealed under vacuum. The polymer reaction solution is reacted at 70°C for 8 hours, the polymerization reaction is quenched with liquid nitrogen, and the reaction tube is opened. The solution is precipitated into an excess of ethyl ether solution (40 mL). The above dissolution-precipitation cycle is repeated three times, then the filter cake is collected by filtration, and dried in a vacuum oven at room temperature overnight to obtain a yellow product. Its structure and molecular weight distribution are characterized by nuclear magnetic resonance hydrogen spectrum and GPC, and the results are shown in Figure 6a 、 Figure 6b 、 Figure 6c 、 Figure 6d 、 Figure 6e as shown, Figure 6epDMSO-33, pDMSO-70, pDMSO-101, pDMSO-195 represent the polymer with degree of polymerization of 33, 70, 101, 195, respectively. When constructing the coating, the hydrophilic polymer coating material is placed in a 1 mM p-toluenesulfonic acid DCM solution to remove the silane protecting group, and after removing the solvent under reduced pressure, it is used.

[0114] Example 4

[0115] This example provides a preparation method of a one-step coatable sulfone-containing polymer coating material, and the reaction synthesis process is as follows:

[0116]

[0117] The specific steps are: 2-(methylsulfonyl)ethyl methacrylate (184 mg, 30 equivalents), AIBN (1.1 mg, 0.2 equivalents) and CTA-DA-TBS (20 mg, 1 equivalent) are dissolved in 0.3 mL DMSO and added to a polymerization reaction tube, the reaction tube is degassed by repeating the freeze-degassing-thaw cycle three times, and sealed under vacuum. The polymer reaction solution is reacted at 70°C for 8 hours, and the polymerization reaction is quenched with liquid nitrogen, and the reaction tube is opened. The solution is precipitated into an excess of ether solution (40 mL). The above dissolution-precipitation cycle is repeated three times, then the filter cake is collected by filtration, and dried in a vacuum oven at room temperature overnight to obtain a white product. Its structure is characterized by nuclear magnetic resonance hydrogen spectrum, and the results are shown in Figure 7 When constructing the coating, the sulfone-containing polymer coating material is placed in a 1 mM p-toluenesulfonic acid DCM solution to remove the silane protecting group, and after removing the solvent under reduced pressure, it is used.

[0118] Example 5

[0119] This example provides a preparation method of a one-step coatable zwitterionic polymer coating material, and the reaction synthesis process is as follows:

[0120]

[0121] Specific steps are: 3-[N, N-dimethyl-[2-(2-methylprop-2-enyl oxy) ethyl] ammonium] propane-1-sulfonic acid inner salt (267 mg, 30 equivalents), AIBN (1.1 mg, 0.2 equivalents) and CTA-DA-TBS (20 mg, 1 equivalent) are dissolved in 0.3 mL of DMSO and added to a polymerization reaction tube, the reaction tube is degassed by repeating the freeze-degassing-thaw cycle three times and sealed under vacuum. The polymer reaction solution is reacted at 70°C for 8 hours, the polymerization reaction is quenched with liquid nitrogen, and the reaction tube is opened. The solution is precipitated into an excess of ethyl ether solution (40 mL). The above dissolution-precipitation cycle is repeated three times, then the filter cake is collected by filtration and dried in a vacuum oven at room temperature overnight to obtain a white product. Its structure is characterized by nuclear magnetic resonance hydrogen spectrum, and the results are shown in Figure 8 When constructing the coating, the zwitterionic polymer coating material is placed in a 1 mM p-toluenesulfonic acid DCM solution to remove the silane protecting group, and then used after removing the solvent under reduced pressure.

[0122] Example 6

[0123] This example provides a preparation method of an oligoethylene glycol polymer coating material that can be coated in one step, and the reaction synthesis process is as follows:

[0124]

[0125] Specific steps are: 3-[N, N-dimethyl-[2-(2-methylprop-2-enyl oxy) ethyl] ammonium] propane-1-sulfonic acid inner salt (267 mg, 30 equivalents), AIBN (1.1 mg, 0.2 equivalents) and CTA-DA-TBS (20 mg, 1 equivalent) are dissolved in 0.3 mL of DMSO and added to a polymerization reaction tube, the reaction tube is degassed by repeating the freeze-degassing-thaw cycle three times and sealed under vacuum. The polymer reaction solution is reacted at 70°C for 8 hours, the polymerization reaction is quenched with liquid nitrogen, and the reaction tube is opened. The solution is precipitated into an excess of ethyl ether solution (40 mL). The above dissolution-precipitation cycle is repeated three times, then the filter cake is collected by filtration and dried in a vacuum oven at room temperature overnight to obtain a white product. Its structure is characterized by nuclear magnetic resonance hydrogen spectrum, and the results are shown in Figure 9 When constructing the coating, the zwitterionic polymer coating material is placed in a 1 mM p-toluenesulfonic acid DCM solution to remove the silane protecting group, and then used after removing the solvent under reduced pressure.

[0126] Example 7

[0127] This example provides a preparation method of an oligoethylene glycol polymer coating material that can be coated in one step, and the reaction synthesis process is as follows:

[0128]

[0129] The specific steps are: poly(ethylene glycol) methyl ether methacrylate (275 mg, 20 equivalents), AIBN (1.1 mg, 0.2 equivalents) and CTA-DA-TBS (20 mg, 1 equivalent) are dissolved in 0.3 mL of DMSO and added to a polymerization reaction tube, which is degassed by repeating the freeze-thaw-degassing cycle three times and sealed under vacuum. The polymerization reaction solution is reacted at 75°C for 12 hours, and the polymerization reaction is quenched with liquid nitrogen, and the reaction tube is opened. The solution is precipitated into an excess of ethyl ether solution (40 mL). The above dissolution-precipitation cycle is repeated three times, and then the filter cake is collected and dried in a vacuum oven at room temperature overnight to obtain a light yellow product. When constructing the coating, the oligoethylene glycol high molecular coating material is placed in a 1 mM p-toluenesulfonic acid DCM solution to remove the silane protecting group, and used after the solvent is removed under reduced pressure.

[0130] Example 8

[0131] This example provides a preparation method of a sulfonium ion high molecular coating material that can be coated in one step. The reaction synthesis process is as follows:

[0132]

[0133] The specific steps are: (2-(acryloyloxy)ethyl)dimethyl sulfonium (643 mg, 10 equivalents), AIBN (6.5 mg, 0.1 equivalents) and CTA-DA-TBS (250 mg, 1 equivalent) are dissolved in 0.5 mL of DMSO and added to a polymerization reaction tube, which is degassed by repeating the freeze-thaw-degassing cycle three times and sealed under vacuum. The polymerization reaction solution is reacted at 80°C for 8 hours, and the polymerization reaction is quenched with liquid nitrogen, and the reaction tube is opened. The solution is precipitated into an excess of ethyl ether solution (40 mL). The above dissolution-precipitation cycle is repeated three times, and then the filter cake is collected and dried in a vacuum oven at room temperature overnight to obtain a white product. When constructing the coating, the sulfonium ion high molecular coating material is placed in a 1 mM p-toluenesulfonic acid DCM solution to remove the silane protecting group, and used after the solvent is removed under reduced pressure.

[0134] Example 9

[0135] Compared with Example 6, the difference is that poly(ethylene glycol) methyl ether methacrylate (60 equivalents), N-(3,4-bis(tert-butyldimethylsiloxy)phenethyl) acrylamide (15 equivalents), AIBN (0.1 equivalents) and CTA-DA-TBS (3 equivalents) are dissolved in 1 mL of DMSO. The polymerization reaction solution is reacted at 80°C for 6 hours.

[0136] Example 10

[0137] Comparing to Example 6, the difference is that poly(ethylene glycol) methyl ether methacrylate (60 equivalents), N-(3,4-bis(tert-butyldimethylsilyloxy)phenethyl)acrylamide (1 equivalent), AIBN (0.2 equivalents) and CTA-DA-TBS (1 equivalent) were dissolved in 0.1 mL DMSO.

[0138] Example 11

[0139] The present embodiment provides a method for preparing a hydrophilic polymer coating, and the specific steps include:

[0140] Different substrates were placed in a vacuum plasma cleaning device, and the medical material was subjected to oxygen plasma treatment under the condition that the radio frequency power was set to 300 W and the gas flow rate was kept at 100 mL / min, thereby obtaining a hydrophilic surface rich in hydroxyl groups. Then, a 10 mM tris(hydroxymethyl)aminomethane solution (121 mg / 100 mL) was used as a buffer system, and the pH value of the solution was adjusted to 8.5. Subsequently, the silane-protected hydrophilic polymer coating material in Example 2 was dissolved in the above buffer system and configured to 2 mg / mL. The medical material subjected to oxygen plasma treatment was immersed in the above configured solution, and the reaction was allowed to proceed for 24 hours. After the reaction was completed, ultrasonic cleaning was performed, and nitrogen was blown dry for subsequent use. The results were detected and verified by X-ray photoelectron spectroscopy, and the results are shown in Figure 10 Bare indicates an untreated medical material, and pDMSO indicates a medical material after coating, wherein the increase of sulfur element proves the effective construction of the coating.

[0141] Example 12

[0142] In the preparation of the coating, the density of the surface hydroxylation can be adjusted by adjusting the radio frequency power and gas flow rate of the plasma cleaning machine. Further, the binding rate of the surface coating on the hydroxyl-rich surface can be adjusted by adjusting the concentration of the tris(hydroxymethyl)aminomethane solution and the soaking time, thereby affecting the construction thickness of the coating.

[0143] The specific steps are as follows: under the conditions of setting the radio frequency power at 100 W and keeping the gas flow rate at 100 mL / min, the medical tube material is treated, then the silane-protected hydrophilic polymer coating material in Example 2 is dissolved in a 10 mM tris(hydroxymethyl)aminomethane solution as a buffer system, configured at 2 mg / mL, the medical material subjected to oxygen plasma treatment is immersed in the solution configured as above, and the reaction is allowed to proceed for 6 hours to obtain a functional coating with a thickness of about 100 nm; without changing other conditions, the tris(hydroxymethyl)aminomethane solution concentration is increased to 20 mM, and after the same 6 hours of immersion, a functional coating with a thickness of about 500 nm is obtained; without changing other conditions, the radio frequency power is set to 200 W and the gas flow rate is kept at 500 mL / min, and after the same 6 hours of immersion, a functional coating with a thickness of about 1000 nm is obtained.

[0144] Example 13

[0145] Compared with Example 11, the difference is that a 15 mM tris(hydroxymethyl)aminomethane solution is used as a buffer system, and the pH value of the solution is adjusted to 8.

[0146] Example 14

[0147] Compared with Example 11, the difference is that a 20 mM tris(hydroxymethyl)aminomethane solution is used as a buffer system, and the pH value of the solution is adjusted to 9.

[0148] The coating prepared in Example 11 is characterized and verified for performance:

[0149] Platelet adhesion experiment, blood analyzer quantitative analysis and biocompatibility evaluation:

[0150] First, 1 mL of whole blood containing 3.2%-3.8% sodium citrate as an anticoagulant is taken from 3 mL of whole blood as a blank control, and incubated at 37°C for 6-7 h. At the same time, heparin grafted medical material (Hep) is taken as a control and immersed in 1 mL of the remaining whole blood together with untreated medical material (Bare) and medical material coated with the hydrophilic polymer coating of Example 2 (pDMSO) at 37°C for 6-7 h. The blood analyzer is used to quantitatively analyze several blood cells in different blood samples to obtain the content of blood cells adhered to the surface of the medical material, evaluate the anticoagulation effect and biocompatibility of the hydrophilic polymer coating, and compare with the heparin anticoagulation coating.

[0151] The results are shown in Table 1. Figure 11 The results show that: Figure 11The platelet adhesion amount of the medical material surface coated with the hydrophilic polymer coating material is significantly different from that of the bare material, and provides better anticoagulation performance; and is not significantly different from that of the heparin anticoagulation coating, the platelet adhesion amount of the medical material surface coated with the hydrophilic polymer coating is less than 5%, which is much lower than that of the bare material surface, and has excellent anticoagulation performance.

[0152] Biofilm adhesion experiment:

[0153] The heparin coating and the hydrophilic polymer coating in Example 2 are respectively constructed on the surface of a 14mm glass slide, and then placed in a sterilized 24-well plate. The Pseudomonas aeruginosa PAO1 strain is selected to grow into a biofilm. Two PAO1 colonies are cultured in LB (4mL) at 37°C with a speed of 200rpm for 16h, then diluted 100 times, and cultured again in a shaker for 4h, then inoculated into the 24-well plate with the coated glass slide, 1mL per group per well, cultured in a 37°C incubator for 72h, and the medium is replaced every 24h for 700μL. Crystal violet staining: the suspension is sucked out, the remaining biofilm is washed once with PBS (1mL), and then crystal violet staining agent (500μL) is added for 20min. Then the crystal violet staining agent is sucked out, and the biofilm is washed with 1mL PBS for 3 times. Then the remaining biofilm stained with crystal violet is dissolved in ethanol (1mL), and the OD 550 is measured by an enzyme marker to quantify the bacterial adhesion on different surfaces.

[0154] The results are shown in Figure 12 The results show that: Figure 12 The bacterial adhesion amount of the glass slide coated with the hydrophilic polymer coating (pDMSO) is significantly different from that of the bare material (Bare), which is much lower than that of the bare material surface, and is lower than that of the glass slide with heparin coating (Hep), which provides better antibacterial adhesion performance. As shown in Figure 14 The schematic diagram of the polymer coating of the application resisting bacterial adhesion is shown.

[0155] Antibacterial activity evaluation:

[0156] Heparin coated and high molecular hydrophilic coating of Example 2 were constructed on 14mm glass slides, respectively, and then placed in sterilized 24-well plates. E. coli was used for antibacterial activity evaluation, two E. coli colonies were cultured in LB (4mL) at 37°C with 200rpm shaking for 16h, then diluted 100-fold and cultured again for 4h before inoculating into the 24-well plates with coated glass slides, and incubated in a 37°C incubator for 24h. The incubated samples were washed twice with sterile PBS and covered with SYTO 9 / propidium iodide staining solution. The samples were placed at room temperature for 20min in the dark, then gently rinsed once with sterile PBS. Then the samples were imaged using a confocal laser scanning microscope. Live bacteria with intact cell membranes were stained green, while dead bacteria with damaged cell membranes were stained red. Images were collected using 488nm excitation and emission filters of 500-550nm (green) and 605-720nm (red).

[0157] The results are shown in Figure 13 The results show that: Figure 13 The surfaces of the glass slides coated with hydrophilic polymer coating (pDMSO) have significantly fewer live and dead bacteria than the surfaces of the heparin coated glass slides (Hep) and bare material (Bare).

[0158] On this basis, it should also be noted that the base material can be plastic, alloy or ceramic in other embodiments of the application.

[0159] In addition, the inventors have also carried out tests with other raw materials, process operations and process conditions described in the specification, and have obtained relatively ideal results.

[0160] The above-described embodiments only express several embodiments of the application, which are described in more detail and in detail, but should not be understood as limiting the scope of the patent. It should be noted that for ordinary skilled in the art, without departing from the concept of the application, a number of modifications and improvements can be made, which are within the scope of the application. Therefore, the scope of protection of the patent of the application should be subject to the appended claims.

Claims

1. A high molecular functional coating material, characterized by, The high-molecular functional coating material has a structure as shown in formula (I): wherein R includes any one of a group containing a sulfide structure, a group containing a sulfonium ion structure, a group containing a sulfoxide structure, a group containing a sulfone structure, a group containing a zwitterion structure, a group containing an oligoethylene glycol structure, or a combination of two or more thereof; n is any integer between 1 and 200; x and y represent molar proportions of copolymerization units, x+y=1, 0≤x<1, and 0<y≤1; The preparation method of the high-molecular functional coating material includes mixing a chain transfer agent having a catechol and / or catechol derivative structure and a functional monomer, and performing a reversible addition-fragmentation chain transfer polymerization reaction to obtain the high-molecular functional coating material. Alternatively, the preparation method of the high-molecular functional coating material includes mixing a chain transfer agent having a catechol and / or catechol derivative structure, a monomer having a catechol and / or catechol derivative structure, and a functional monomer, and performing a reversible addition-fragmentation chain transfer polymerization reaction to obtain the high-molecular functional coating material. The functional monomer includes any one of a monomer containing a sulfide structure, a monomer containing a sulfonium ion structure, a monomer containing a sulfoxide structure, a monomer containing a sulfone structure, a monomer containing a zwitterion structure, a monomer containing an oligoethylene glycol structure, or a combination of two or more thereof. The molar ratio of the chain transfer agent having a catechol and / or catechol derivative structure, the monomer having a catechol and / or catechol derivative structure, and the functional monomer is (1-5):(1-30):(10-200). The chain transfer agent having a catechol and / or catechol derivative structure has a structure as shown in formula (II):

2. The polymeric functional coating material according to claim 1, wherein: The polymerization temperature of the reversible addition-fragmentation chain transfer polymerization is 70-80°C, and the polymerization time is 6-12h.

3. The polymeric functional coating material according to claim 1, wherein The monomer having a catechol and / or catechol derivative structure has a structure as shown in at least any one of formula (III) or formula (IV):

4. A high molecular functional coating, characterized by, The high-molecular functional coating material of any one of claims 1-3 is applied to the surface of a substrate to obtain; the thickness of the coating is 100-2000nm.

5. The method of claim 4, wherein the polymer functional coating is prepared by the steps of: The method comprises: The surface of a substrate is subjected to a hydroxylated hydrophilic modification treatment, and then the high-molecular functional coating material is applied to the surface of the substrate in a buffer system to obtain the high-molecular functional coating.

6. The preparation method according to claim 5, characterized in that, The substrate includes any one of polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene, expanded polytetrafluoroethylene, polylactic acid, polycarbonate, polyurethane, polystyrene, polysulfone, polyethersulfone, polyacrylonitrile, polymethacrylate, latex, silicone rubber, glass, ceramic, stainless steel, titanium alloy, nickel-titanium alloy, or a combination of two or more thereof.

7. The preparation method according to claim 5, characterized in that, The hydroxylated hydrophilic modification treatment includes placing the substrate in a vacuum plasma cleaning machine, and subjecting the substrate to oxygen plasma treatment under the conditions of a radio frequency power of 100-300W and a gas flow rate of 100-500mL / min to obtain a hydrophilic surface rich in hydroxyl groups.

8. The preparation method according to claim 5, characterized in that, The buffer system includes a tris(hydroxymethyl)aminomethane solution buffer system.

9. The preparation method according to claim 5, characterized in that, The pH value of the buffer system is 8-9.

10. Use of the high-molecular functional coating material as claimed in claims 1 to 3 or the high-molecular functional coating as claimed in claim 4 in the field of protection of medical materials.

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