Endothelialization-promoting antifouling developing coating material as well as preparation method and application thereof

Abstract

The invention relates to an endothelialization-promoting antifouling developing coating material as well as a preparation method and application thereof. The endothelialization-promoting antifouling developing coating material is obtained by reacting a siloxane-modified developing agent with a modified phosphorylcholine polymer; the modified phosphorylcholine polymer is obtained by copolymerization of a double-bond-containing monomer, and the double-bond-containing monomer comprises a combination of a double-bond-containing phosphorylcholine monomer, an endothelialization-promoting monomer and a siloxane monomer. According to the endothelialization-promoting antifouling developing coating material disclosed by the invention, a siloxane-modified developing agent is connected with a modified phosphorylcholine polymer. The siloxane-modified developing agent improves the developing function, and the modified phosphorylcholine polymer provides antifouling and endothelialization promoting functions, so that a composite coating with antifouling, developing and endothelialization promoting functions is formed.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to an endothelialization-promoting anti-fouling and developing coating material, a preparation method thereof, and an application thereof. Background Art

[0002] In the fields of medical imaging and implantable medical devices, the development of medical imaging coatings is key to improving diagnostic and treatment accuracy and device safety. With the advancement of interventional therapy, the requirements for imaging coatings have expanded from a single imaging function to multifunctional integration, including anti-fouling (anti-thrombotic, antibacterial) and endothelialization-promoting properties to meet the needs of complex clinical scenarios.

[0003] Traditional developing coatings mainly rely on iodine compounds (such as iohexol) or heavy metal-containing developers to achieve imaging functions through interaction with X-rays. However, such coatings face problems of developer dissolution and poor biocompatibility during long-term implantation, and lack active anti-fouling capabilities, which can easily cause thrombosis or infection. In order to meet the anti-fouling needs, existing technologies introduce anti-fouling materials such as phosphorylcholine polymers and polyethylene glycol (PEG) to reduce protein and bacterial adsorption by using their hydrophilic or cell membrane-mimicking structures. Although such coatings can improve anti-fouling performance, their developing function is often attenuated due to insufficient compatibility between the developer and the anti-fouling group, and phase separation is prone to occur in the body fluid environment, resulting in decreased coating stability.

[0004] In recent years, researchers have attempted to synergistically integrate the development and antifouling functions. For example, siloxane groups are used to enhance the bonding between the coating and the substrate, while iodine groups are used to provide development functions. However, such coatings still have two major defects: first, the simple physical mixing of the developer and the antifouling group leads to the loss of functional components during long-term use; second, the biological inertness of the coating surface, while it can reduce the adhesion of pollutants, inhibits the adhesion and proliferation of endothelial cells, resulting in delayed endothelialization of the surface of implanted devices (such as cardiovascular stents), increasing the risk of postoperative restenosis.

[0005] CN103467729A discloses a polyethylene glycol-polyamino acid-polyester triblock polymer that can form amphiphilic micelles as a carrier for a contrast agent. However, the contrast agent and the antifouling group are physically combined, and the functional components are easily lost during long-term use.

[0006] CN119219844A discloses an antifouling and developing coating material that combines antifouling and developing properties through covalent bonding technology, ensuring the stability and durability of the developing effect. However, the coating surface of this material is biologically inert, inhibiting the adhesion and proliferation of endothelial cells.

[0007] CN119101421A discloses an antifouling and developing coating material that combines platinum nanoparticles with modified phosphorylcholine polymers, resulting in an antifouling and developing coating material with both excellent antifouling and developing properties. Furthermore, the siloxane groups in the antifouling units can form covalent bonds with the substrate surface, firmly bonding the coating to the substrate and ensuring the stability and safety of the antifouling and developing coating material on the substrate. However, the developer in this material is platinum nanoparticles, which are electrostatically bonded to the polymer chains, resulting in poor stability.

[0008] In the field of endothelialization-promoting coatings, existing technologies primarily promote endothelial cell growth by grafting bioactive molecules. For example, vascular stent coatings modified with RGD peptides can specifically bind to endothelial cell integrin receptors, accelerating endothelial repair. However, such coatings lack visualization and antifouling properties, and the physical adsorption or simple covalent attachment of RGD peptides can easily lead to shedding or loss of activity, especially under the shear forces of blood flow. Furthermore, while heparin coatings have the dual effects of anticoagulation and endothelialization, their bioactivity relies on precise molecular weight control and carries the risk of inducing thrombocytopenia.

[0009] In summary, the existing technologies for developing, antifouling, and promoting endothelialization coatings are functionally separate, making it difficult to meet the synergistic needs of implantable devices for developing monitoring, antifouling and anti-thrombosis, and rapid endothelial repair. Therefore, effectively combining developing, antifouling, and endothelial repair functions remains a challenging issue that requires further research. Summary of the Invention

[0010] To solve the above technical problems, the present invention provides an endothelialization-promoting anti-fouling and developing coating material, its preparation method, and application. The endothelialization-promoting anti-fouling and developing coating material of the present invention meets the synergistic needs of implantable devices for development monitoring, anti-fouling and anti-thrombosis, and rapid endothelial repair.

[0011] To achieve this object, the present invention adopts the following technical solutions:

[0012] In a first aspect, the present invention provides an endothelialization-promoting antifouling and developing coating material, wherein the endothelialization-promoting antifouling and developing coating material is obtained by reacting a siloxane-modified developer with a modified phosphorylcholine polymer;

[0013] The modified phosphorylcholine polymer is obtained by copolymerizing double-bond-containing monomers, wherein the double-bond-containing monomers include a combination of double-bond-containing phosphorylcholine monomers, endothelialization-promoting monomers, and siloxane monomers;

[0014] The endothelialization-promoting monomer is obtained by reacting the endothelialization-promoting polypeptide with NHS-polyethylene glycol-acrylate;

[0015] The structure of the siloxane monomer is shown in Formula I: X includes hydrogen and / or methyl, and R includes a tris(trimethylsiloxy)silane group and / or a trimethoxysilane group;

[0016] The R group is connected to the siloxane-modified developer through a chemical bond.

[0017] The present invention's endothelialization-promoting antifouling and developing coating material combines a siloxane-modified developer with a modified phosphorylcholine polymer. The siloxane-modified developer enhances development, while the modified phosphorylcholine polymer provides both antifouling and endothelialization-promoting properties, resulting in a composite coating that combines antifouling, developing, and endothelialization-promoting functions. By selecting specific polymerizable monomers, the present invention combines these three functions in a single polymer. The addition of the siloxane monomer also enhances the material's bonding properties.

[0018] Preferably, the double bond-containing monomer comprises the following components in molar parts: 10-30 parts of a double bond-containing phosphorylcholine monomer, 10-30 parts of a siloxane monomer, and 1-5 parts of an endothelialization-promoting monomer.

[0019] The molar fraction of the double-bond phosphorylcholine monomer can be, for example, 15 parts, 18 parts, 20 parts, 25 parts or 28 parts.

[0020] The molar fraction of the siloxane monomer may be, for example, 15 parts, 18 parts, 20 parts, 25 parts, or 28 parts.

[0021] The molar fraction of the endothelialization-promoting monomer can be, for example, 2 parts, 3 parts, or 4 parts.

[0022] Preferably, the double bond-containing monomer comprises the following components in parts by mass: 1-5 parts of a double bond-containing phosphorylcholine monomer, 1-10 parts of a siloxane monomer, and 1-5 parts of an endothelialization-promoting monomer.

[0023] The weight fraction of the double-bond phosphorylcholine monomer may be, for example, 2 parts, 3 parts, or 4 parts.

[0024] The mass fraction of the siloxane monomer may be, for example, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts or 9 parts.

[0025] The weight fraction of the endothelialization-promoting monomer may be, for example, 2 parts, 3 parts, or 4 parts.

[0026] Preferably, the double-bond-containing phosphorylcholine monomer includes 2-methacryloyloxyethyl phosphorylcholine and / or acryloyloxyethyl phosphorylcholine.

[0027] Preferably, the siloxane monomer includes any one or a combination of at least two of the following compounds:

[0028]

[0029] Preferably, the sequence of the endothelialization-promoting polypeptide includes any one of GGYIGSR or GGREDV, or a combination of both.

[0030] Preferably, the siloxane-modified developer is obtained by reacting a silane coupling agent with a developer.

[0031] Preferably, the silane coupling agent includes Any one of 3-glycidyloxypropyltriethoxysilane, 3-glycidyloxypropylmethyldimethoxysilane or 2-(3,4-epoxycyclohexyl)ethyltriethoxysilane, or a combination of at least two thereof.

[0032] Preferably, the developer comprises any one of iohexol, iohexol hydrolyzate, iopromide, meglumine diatrizoate, sodium diatrizoate, iodized oil or iodixanol, or a combination of at least two thereof, and more preferably iohexol and / or iohexol hydrolyzate.

[0033] Preferably, the siloxane-modified developer is connected to the R group via a Si-O-Si bond.

[0034] In a second aspect, the present invention provides a method for preparing the endothelialization-promoting antifouling and developing coating material according to the first aspect, the preparation method comprising the following steps:

[0035] Copolymerizing a siloxane monomer, an endothelialization-promoting monomer, and a double-bond phosphorylcholine monomer to obtain a modified phosphorylcholine polymer;

[0036] The siloxane-modified developer is subjected to a first hydrolysis-condensation reaction with the modified phosphorylcholine polymer to obtain the endothelialization-promoting anti-fouling developing coating material.

[0037] Preferably, the preparation method of the endothelialization-promoting monomer comprises:

[0038] The endothelialization-promoting polypeptide is subjected to a condensation reaction with NHS-polyethylene glycol-acrylate to obtain the endothelialization-promoting monomer.

[0039] Preferably, the condensation reaction is carried out in the presence of a catalyst.

[0040] Preferably, the catalyst comprises triethylamine.

[0041] Preferably, the molar ratio of the endothelialization-promoting polypeptide to NHS-polyethylene glycol-acrylate is (1-5):1, for example, 2:1, 3:1, or 4:1.

[0042] Preferably, the temperature of the condensation reaction is 15-45°C, for example, 20°C, 25°C, 30°C, 35°C or 40°C, etc., preferably 28-32°C.

[0043] Preferably, the condensation reaction time is 1-5 h, for example, 1.5 h, 2.5 h, 3 h, 3.5 h or 4.5 h, etc., preferably 2-4 h.

[0044] Preferably, the solvent for the condensation reaction includes N,N-dimethylformamide.

[0045] Preferably, the condensation reaction is carried out under the protection of protective gas.

[0046] Preferably, the protective gas comprises nitrogen.

[0047] Preferably, the preparation method of the siloxane-modified developer comprises:

[0048] The developer and the silane coupling agent undergo a second hydrolysis-condensation reaction to obtain the siloxane-modified developer.

[0049] Preferably, the molar ratio of the developer to the silane coupling agent is (1-3):1, for example, 1.5:1, 2:1 or 2.5:1.

[0050] Preferably, the temperature of the second hydrolysis condensation reaction is 15-30°C, for example, 16°C, 18°C, 23°C, 26°C or 28°C, etc., preferably 20-25°C.

[0051] Preferably, the second hydrolysis condensation reaction time is 12-24 hours, for example, it can be 14 hours, 16 hours, 18 hours, 20 hours or 22 hours.

[0052] Preferably, the solvent for the second hydrolysis condensation reaction includes a mixture of water and an organic solvent, and the organic solvent includes any one of methanol, isopropanol, n-propanol, and dimethyl sulfoxide, or a combination of at least two thereof.

[0053] Preferably, the copolymerization reaction is carried out in the presence of an initiator.

[0054] Preferably, the initiator includes any one of azobisisobutyronitrile, dibenzoyl peroxide, or 4,4'-azobis(4-cyanovaleric acid), or a combination of at least two thereof, preferably azobisisobutyronitrile.

[0055] Preferably, the copolymerization reaction is carried out in the presence of a solvent.

[0056] Preferably, the solvent for the copolymerization reaction includes any one of n-propanol, dimethyl sulfoxide, tetrahydrofuran, toluene or ethyl acetate, or a combination of at least two thereof, preferably n-propanol.

[0057] Preferably, the copolymerization is carried out in the presence of a chain transfer agent.

[0058] Preferably, the chain transfer agent for the copolymerization reaction includes any one of N,N-dimethyldithiocarbamate, polyethylene glycol-modified trithiocarbonate or 4-cyano-4-(thiobenzoyl)valeric acid, or a combination of at least two thereof, preferably 4-cyano-4-(thiobenzoyl)valeric acid.

[0059] Preferably, the copolymerization reaction temperature is 60-70°C, for example, 62°C, 64°C, 66°C or 68°C.

[0060] Preferably, the copolymerization reaction time is 28-56 h, for example, 30 h, 35 h, 40 h, 45 h, 50 h or 55 h.

[0061] Preferably, the temperature of the first hydrolysis condensation reaction is 20-30°C, for example, 22°C, 24°C, 26°C or 28°C.

[0062] Preferably, the first hydrolysis condensation reaction time is 3-12 h, for example, 4 h, 6 h, 8 h or 10 h, etc., preferably 5-7 h.

[0063] Preferably, the first hydrolysis condensation reaction is carried out in the presence of a solvent.

[0064] Preferably, the solvent for the first hydrolysis condensation reaction includes a mixture of water and an organic solvent, and the organic solvent includes any one of methanol, isopropanol, n-propanol, and dimethyl sulfoxide, or a combination of at least two thereof.

[0065] Preferably, in the first hydrolysis condensation reaction, the molar ratio of the siloxane-modified developer to the siloxane repeating unit in the modified phosphorylcholine polymer is (0.5-2):1, for example, 0.75:1, 1:1, 1.25:1, 1.6:1 or 1.75:1, and more preferably (0.8-1.5):1.

[0066] The present invention achieves improved developing performance while enhancing the adhesion of the coating by adjusting the molar ratio of the siloxane-modified developer to the siloxane repeating units in the modified phosphorylcholine polymer to (0.5-2):1. Excessive molarity of the siloxane-modified developer reduces the antifouling effect, while excessive molarity of the siloxane repeating units in the modified phosphorylcholine polymer reduces the developing effect.

[0067] In a third aspect, the present invention provides a use of the endothelialization-promoting anti-fouling and developing coating material as described in the first aspect in medical devices, medical materials or optical lenses.

[0068] In a fourth aspect, the present invention provides a use of the endothelialization-promoting antifouling developing coating material as described in the first aspect in coating a substrate surface.

[0069] Preferably, the substrate surface includes any one of a silicon-based surface, a glass-based surface, a metal-based surface, and a high-molecular polymer-based surface, or a combination of at least two thereof.

[0070] Preferably, the polymer includes any one of silicone rubber, polyethylene, polypropylene, polyvinyl chloride, polystyrene or polyurethane, or a combination of at least two thereof.

[0071] The endothelialization-promoting anti-fouling developing coating material of the present invention has universal applicability. It combines with the hydroxyl groups on the surface of the substrate through silicon-oxygen bonds and can achieve covalent bonding with any silicon-based substrate, including glass, silicone sheets, metal oxide surfaces, etc.; it combines with other substrate surfaces through hydrophobic interaction or van der Waals force, and is widely applicable to different clinical and laboratory scenarios to meet the needs of different users.

[0072] Compared with the prior art, the present invention has at least the following beneficial effects:

[0073] (1) The endothelialization-promoting antifouling and developing coating material of the present invention combines antifouling, developing, and endothelialization-promoting functions. Compared with traditional developing coatings, the antifouling performance of this material is significantly improved, effectively inhibiting nonspecific bacterial adsorption and reducing the risk of infection. The developer is chemically embedded in the coating network to prevent water-soluble loss and ensure the long-term stability of the developing signal in the body. At the same time, the covalently bonded endothelialization-promoting polypeptide promotes endothelial cell adhesion and proliferation.

[0074] (2) The present invention can promote the stable covalent bonding of the coating to various surfaces by adjusting the molar ratio of the siloxane-modified developer to the siloxane repeating unit in the modified phosphorylcholine polymer. BRIEF DESCRIPTION OF THE DRAWINGS

[0075] Figure 1 A is the H NMR spectrum of Example 2;

[0076] Figure 1 B is the H NMR spectrum of Example 1;

[0077] Figure 1 C is the H NMR spectrum of Example 3;

[0078] Figure 1 D is the photoelectron spectrum of Examples 1-3;

[0079] Figure 2 A is a graph showing the results of the antibacterial adhesion test of the endothelialization-promoting antifouling developing coating material of Example 1;

[0080] Figure 2 B is a quantitative analysis result of the anti-bacterial adhesion test of the endothelialization-promoting antifouling developing coating material of Example 1;

[0081] Figure 3A is a graph showing the development test results of the endothelialization-promoting antifouling developing coating material in Example 1 in a rat;

[0082] Figure 3 B is a diagram showing the quantitative analysis results of the development of the endothelialization-promoting antifouling developing coating material in rat tissue according to Example 1;

[0083] Figure 4 A is a graph showing the endothelialization-promoting test results of the endothelialization-promoting anti-fouling developing coating materials of Example 1, Example 4 and Comparative Example 1 on a glass substrate;

[0084] Figure 4 B is a diagram showing the quantitative analysis results of the endothelialization-promoting anti-fouling developing coating materials of Example 1, Example 4 and Comparative Example 1 on a glass substrate. DETAILED DESCRIPTION

[0085] The technical solution of the present invention will be further described below with reference to the accompanying drawings and through specific embodiments. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

[0086] Example 1

[0087] This embodiment provides an endothelialization-promoting anti-fouling and developing coating material, and a preparation method of the endothelialization-promoting anti-fouling and developing coating material comprises the following steps:

[0088] (1) Preparation of endothelialization-promoting monomers

[0089] 2.0 mol of the polypeptide (GGYIGSR) was dissolved in anhydrous DMF and placed in an ice bath. 1 mol of NHS-PEG-acrylate (manufacturer: MCE, brand: HY-172354A) in DMF was slowly added dropwise and stirred at room temperature for 3 h. Excess glycine was added and incubated at room temperature for 10 min to quench the reaction. Small molecules were removed by dialysis and the mixture was freeze-dried to obtain the endothelial-promoting monomer.

[0090]

[0091] (2) Preparation of modified phosphorylcholine polymer

[0092]

[0093] 2-Methacryloxyethyl phosphorylcholine (3g), 4-cyano-4-(thiobenzoyl)valeric acid (3g), and azobisisobutyronitrile (AIBN, 0.16g) were dissolved in n-propanol (100mL). Under nitrogen protection, the temperature was slowly raised to 65°C and stirred for 24 hours. Then, methacryloxypropyltris(trimethylsiloxy)silane (8mL) and 1.5g of endothelialization monomer were added and the reaction was continued for 24 hours. The resulting solution was added to diethyl ether (200mL) for precipitation and filtered and dried to obtain a modified phosphorylcholine polymer.

[0094] (3) Preparation of siloxane-modified developer

[0095] Iohexol hydrolyzate (5 g) was dissolved in 10 mL of a methanol / water binary mixed solvent (methanol / water volume ratio was 1:1), and potassium hydroxide (1.67 g) was added and stirred at room temperature and ultrasonicated to fully dissolve the mixture to obtain a light yellow solution. (2g) was dissolved in 10 mL of a methanol / water binary solvent mixture, which was then mixed with the pale yellow solution and stirred at room temperature overnight. The product was then extracted from the methanol / water binary solvent into the organic phase using ethyl acetate, and the extraction was repeated five times. The reaction mixture was then evaporated using a rotary evaporator to remove the organic solvent, followed by dialysis and liquid phase processing to obtain a siloxane-modified developer.

[0096] (4) Preparation of endothelialization-promoting antifouling developing coating materials

[0097] A siloxane-modified developer and a modified phosphorylcholine polymer were mixed in a methanol / water binary solvent (methanol / water volume ratio of 1:1), with a molar ratio of 1:1 between the siloxane-modified developer and the siloxane repeating units in the modified phosphorylcholine polymer. The mixture was stirred at room temperature for 6 hours, extracted with ethyl acetate, and rotary evaporated to obtain an endothelialization-promoting anti-fouling developer coating material.

[0098] Example 2

[0099] This embodiment provides an endothelialization-promoting antifouling and developing coating material, which differs from Example 1 only in that (4) the preparation of the endothelialization-promoting antifouling and developing coating material comprises the following steps: mixing a siloxane-modified developer and a modified phosphorylcholine polymer in a methanol / water binary solvent (methanol / water volume ratio of 1:1), wherein the molar ratio of the siloxane-modified developer to the siloxane repeating unit in the modified phosphorylcholine polymer is 2:1. The mixture is stirred at room temperature for 6 hours, extracted with ethyl acetate, and rotary evaporated to obtain the endothelialization-promoting antifouling and developing coating material.

[0100] Example 3

[0101] This embodiment provides an endothelialization-promoting antifouling and developing coating material, which differs from Example 1 only in that (4) the preparation of the endothelialization-promoting antifouling and developing coating material comprises the following steps: mixing a siloxane-modified developer and a modified phosphorylcholine polymer in a methanol / water binary solvent (methanol / water volume ratio of 1:1), wherein the molar ratio of the siloxane-modified developer to the siloxane repeating unit in the modified phosphorylcholine polymer is 1:2. The mixture is stirred at room temperature for 6 hours, extracted with ethyl acetate, and rotary evaporated to obtain the endothelialization-promoting antifouling and developing coating material.

[0102] like Figure 1 As shown, the endothelialization-promoting antifouling developing coating materials provided in Examples 1-3 were characterized by nuclear magnetic resonance and photoelectron spectroscopy (XPS). The nuclear magnetic resonance hydrogen spectrum curve had vibration peaks at 7.3ppm and 3.55ppm, corresponding to the iodine phenyl group in the developing monomer and the siloxane group in the antifouling molecule, respectively; the XPS curve detected peaks at 285eV, 532eV, 400eV, and 620eV, corresponding to C, O, N, and I elements, respectively, and with the increase of the proportion of iodine-containing developing monomers, the I element content of the sample increased from 2% to 4%, proving the successful polymerization of the iodine-containing developing monomers and the antifouling molecules.

[0103] Example 4

[0104] A endothelialization-promoting antifouling and developing coating material, which differs from Example 1 only in that the polypeptide sequence in step (1) is GGREDV, and the remaining steps are the same as Example 1.

[0105] Comparative Example 1

[0106] An endothelialization-promoting antifouling developing coating material is disclosed. The difference between the material and Example 1 is that no endothelialization-promoting monomer is added in step (2), and the remaining steps are the same as those in Example 1.

[0107] Test Method

[0108] (1) Antibacterial adhesion test

[0109] The antibacterial adsorption ability of the coating was tested using Candida albicans (C.albicans), Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus). The endothelialization-promoting antifouling developing coating material was applied to the glass surface and the sample was immersed in a high concentration (10 8 The live bacteria were replaced daily in three different live bacterial solutions (1000 cells / mL). After soaking for one week, the samples were removed and air-dried, and the bacterial counts were observed using a scanning electron microscope (SEM). The dialysate was used as the solvent to ensure bacterial activity. A blank control group consisted of samples not coated with the coating material.

[0110] The results of the antibacterial adhesion test were as follows Figure 2As shown in A, under the adsorption of three different bacteria, after one week, the control group without antifouling developing coating had obvious large colonies, while no obvious colony growth was observed on the sample coated with antifouling developing coating. Further, the adsorbed colonies were quantitatively analyzed, and the results were as follows: Figure 2 As shown in Figure B, the sample using the antifouling developing coating significantly reduced bacterial adhesion, with the amount of bacterial adhesion reduced by 90% after one week.

[0111] (2) X-ray imaging test

[0112] The antifouling developing coating material of the present invention was coated on a silicone hose and placed in a rat body. The coating solution concentration was 100 mg / mL and 200 mg / mL. The control group was a silicone hose not coated with the antifouling developing coating material. The rat body was photographed using a medical X-ray irradiator (manufacturer: Frameview Dexin; model: XVS2530).

[0113] Figure 3 A is the X-ray development photograph of different concentrations of development materials; Figure 3 B represents the grayscale value of the developer material at different concentrations. This indicates that the anti-fouling developer coating material of the present invention exhibits a significantly higher development efficiency than the blank control. Quantitative analysis of the developed portion using Image J software reveals that the development intensity within the rat increases with increasing concentration. This demonstrates that the anti-fouling developer coating material of the present invention exhibits a strong X-ray development effect.

[0114] (3) Endothelialization test

[0115] The endothelialization-promoting antifouling coating material was applied to a glass surface. An uncoated group served as a negative control, while an antifouling coating without an endothelialization-promoting group served as a positive control. Cell attachment was observed after 0, 4, and 24 hours of incubation. (Cell information: HUVEC cells; cultured at 37°C, 5% CO2)

[0116] Figure 4 A is the cell adhesion diagram of the endothelialization-promoting antifouling developing coating on the glass substrate at different times. Figure 4 B is a statistical diagram of the number of cells adhered to the endothelialization-promoting antifouling developing coating on the glass substrate after 24 hours; it can be seen that the endothelialization-promoting effect of the present invention is much higher than that of the positive control group, which shows that the present invention has a strong endothelialization-promoting effect.

[0117] The applicant declares that the above is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention fall within the scope of protection and disclosure of the present invention.

Claims

1. A endothelialization-promoting antifouling developing coating material, characterized in that: The endothelialization-promoting antifouling developing coating material is obtained by reacting a siloxane-modified developer with a modified phosphorylcholine polymer; The modified phosphorylcholine polymer is obtained by copolymerizing double-bond-containing monomers, wherein the double-bond-containing monomers include a combination of double-bond-containing phosphorylcholine monomers, endothelialization-promoting monomers, and siloxane monomers; The endothelialization-promoting monomer is obtained by reacting the endothelialization-promoting polypeptide with NHS-polyethylene glycol-acrylate; The structure of the siloxane monomer is shown in Formula I: wherein X comprises hydrogen and / or methyl, and R comprises tris(trimethylsiloxy)silane group and / or trimethoxysilane group; The R group is connected to the siloxane-modified developer through a chemical bond.

2. The endothelialization-promoting antifouling developing coating material according to claim 1, characterized in that: The double bond-containing monomer comprises the following components in molar parts: 10-30 parts of double bond-containing phosphorylcholine monomer, 10-30 parts of siloxane monomer, and 1-5 parts of endothelialization-promoting monomer.

3. The endothelialization-promoting antifouling developing coating material according to claim 1 or 2, characterized in that: The double-bond phosphorylcholine monomer includes 2-methacryloyloxyethyl phosphorylcholine and / or acryloyloxyethyl phosphorylcholine; Preferably, the siloxane monomer includes any one or a combination of at least two of the following compounds: Preferably, the sequence of the endothelialization-promoting polypeptide includes any one of GGYIGSR or GGREDV, or a combination of both.

4. The endothelialization-promoting antifouling developing coating material according to any one of claims 1 to 3, characterized in that: The siloxane-modified developer is obtained by reacting a silane coupling agent with a developer; Preferably, the silane coupling agent includes Any one or a combination of at least two of 3-glycidyloxypropyltriethoxysilane, 3-glycidyloxypropylmethyldimethoxysilane or 2-(3,4-epoxycyclohexyl)ethyltriethoxysilane; Preferably, the developer comprises any one of iohexol, iohexol hydrolyzate, iopromide, meglumine diatrizoate, sodium diatrizoate, iodized oil or iodixanol, or a combination of at least two thereof, and more preferably iohexol and / or iohexol hydrolyzate.

5. The endothelialization-promoting antifouling developing coating material according to any one of claims 1 to 4, characterized in that: The siloxane-modified developer is connected to the R group via a Si-O-Si bond.

6. A method for preparing the endothelialization-promoting antifouling developing coating material according to any one of claims 1 to 5, characterized in that: The preparation method comprises the following steps: Copolymerizing a siloxane monomer, an endothelialization-promoting monomer, and a double-bond phosphorylcholine monomer to obtain a modified phosphorylcholine polymer; The siloxane-modified developer is subjected to a first hydrolysis-condensation reaction with the modified phosphorylcholine polymer to obtain the endothelialization-promoting anti-fouling developing coating material.

7. The preparation method according to claim 6, characterized in that The preparation method of the endothelialization-promoting monomer comprises: The endothelialization-promoting polypeptide is subjected to a condensation reaction with NHS-polyethylene glycol-acrylate to obtain the endothelialization-promoting monomer; Preferably, the condensation reaction is carried out in the presence of a catalyst; Preferably, the catalyst comprises triethylamine; Preferably, the molar ratio of the endothelialization-promoting polypeptide to NHS-polyethylene glycol-acrylate is (1-5):1; Preferably, the temperature of the condensation reaction is 15-45°C, preferably 28-32°C; Preferably, the condensation reaction time is 1-5h, preferably 2-4h; Preferably, the solvent for the condensation reaction comprises N,N-dimethylformamide; Preferably, the condensation reaction is carried out under the protection of protective gas; Preferably, the protective gas comprises nitrogen.

8. The preparation method according to claim 6 or 7, characterized in that The preparation method of the siloxane-modified developer comprises: The developer and the silane coupling agent undergo a second hydrolysis-condensation reaction to obtain the siloxane-modified developer; Preferably, the molar ratio of the developer to the silane coupling agent is (1-3):1; Preferably, the temperature of the second hydrolysis condensation reaction is 15-30°C, preferably 20-25°C; Preferably, the second hydrolysis condensation reaction time is 12-24h; Preferably, the solvent for the second hydrolysis condensation reaction includes a mixture of water and an organic solvent, and the organic solvent includes any one of methanol, isopropanol, n-propanol, and dimethyl sulfoxide, or a combination of at least two thereof.

9. The preparation method according to any one of claims 6 to 8, characterized in that The copolymerization reaction is carried out in the presence of an initiator; Preferably, the copolymerization reaction temperature is 60-70°C; Preferably, the copolymerization reaction time is 28-56h; Preferably, the temperature of the first hydrolysis condensation reaction is 20-30°C; Preferably, the first hydrolysis condensation reaction time is 3-12h, preferably 5-7h; Preferably, the first hydrolysis condensation reaction is carried out in the presence of a solvent; Preferably, the solvent for the first hydrolysis condensation reaction comprises a mixture of water and an organic solvent, and the organic solvent comprises any one of methanol, isopropanol, n-propanol, and dimethyl sulfoxide, or a combination of at least two thereof; Preferably, in the first hydrolysis condensation reaction, the molar ratio of the siloxane-modified developer to the siloxane repeating unit in the modified phosphorylcholine polymer is (0.5-2):1, more preferably (0.8-1.5):

1.

10. Use of the endothelialization-promoting anti-fouling developing coating material according to any one of claims 1 to 5 in medical devices, medical materials or optical lenses.

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