An anti-inflammatory and anti-protein adhesion metal polyphenol protein bilayer coating and its preparation method and application

Abstract

This application discloses an anti-inflammatory and anti-protein adhesion metal polyphenol protein bilayer coating, its preparation method, and its application. The preparation method includes the following steps: preparing an inner layer protein solution with deionized water and an inner layer polyphenol solution with ethanol, then mixing the inner layer protein solution and the inner layer polyphenol solution to obtain an inner layer coating mixture solution; preparing an outer layer protein solution, an outer layer polyphenol solution, and a metal ion solution with deionized water, then mixing the outer layer protein solution, outer layer polyphenol solution, and metal ion solution to obtain an outer layer coating mixture solution; completely immersing the pretreated substrate in the inner layer coating mixture solution and irradiating it with a UV lamp to obtain a modified substrate; placing the modified substrate in the outer layer coating mixture solution and continuing to irradiate it with a UV lamp to obtain a metal polyphenol protein bilayer coating. This application utilizes the outer layer for rapid antibacterial, anti-inflammatory, and anti-tear protein deposition, and the inner layer for deep ROS removal, oxygen production, and sustained anti-inflammatory effects.

Description

Technical Field

[0001] This application relates to the field of polymer materials technology, and in particular to an anti-inflammatory and anti-protein adhesion metal polyphenol protein bilayer coating, its preparation method and application. Background Technology

[0002] Infectious keratitis is a highly threatening blinding eye disease in ophthalmology. Its causes are complex, with bacterial infection from contact lens wear being a key risk factor. The pathophysiology of keratitis is not simply bacterial invasion, but a vicious cycle interwoven with pathogen infection, inflammatory cell infiltration, and reactive oxygen species (ROS) outbreaks. Once the cornea is damaged, large amounts of ROS, such as hydrogen peroxide, are produced in the stroma, leading to severe oxidative stress and further damaging the corneal epithelium and stromal structure. If not controlled in time, it will progress to corneal ulcers or even perforation, causing irreversible visual impairment.

[0003] Besides pathogen invasion, ultraviolet radiation can also induce corneal cells to produce reactive oxygen species, which have a synergistic effect with oxidative damage caused by infection. Long-term exposure of the cornea to ultraviolet radiation can aggravate oxidative stress damage, further destroy the corneal tissue structure, and may induce eye diseases such as cataracts.

[0004] Contact lenses, as wearable drug delivery systems, have attracted widespread attention in recent years due to their advantages such as non-invasiveness, continuous drug delivery, and improved bioavailability. Researchers have attempted to load antibacterial drugs into lens materials to achieve localized continuous drug release. However, most current research on drug-loaded contact lenses focuses on a single antibacterial function, lacking an integrated approach that can simultaneously address infection control, protein deposition, oxidative stress, and UV damage. Summary of the Invention

[0005] To address the existing technical problems, this application provides an anti-inflammatory and anti-protein adhesion metal polyphenol protein bilayer coating, its preparation method, and its application. The technical solution is as follows: In a first aspect, a method for preparing a metal polyphenol protein bilayer coating with anti-inflammatory and anti-protein adhesion properties is provided, comprising the following steps: An inner layer protein solution is prepared using deionized water, and an inner layer polyphenol solution is prepared using ethanol. The inner layer protein solution and the inner layer polyphenol solution are then mixed to obtain an inner layer coating mixture solution. An outer layer protein solution, an outer layer polyphenol solution, and a metal ion solution were prepared using deionized water. Then, the outer layer protein solution, the outer layer polyphenol solution, and the metal ion solution were mixed to obtain an outer coating mixture solution. The pretreated substrate was completely immersed in the inner coating mixture solution and irradiated with an ultraviolet lamp to obtain the modified substrate; The modified matrix is ​​placed in the outer coating mixture solution and irradiated with an ultraviolet lamp to obtain the metal polyphenol protein bilayer coating.

[0006] Furthermore, the concentration of the inner layer protein solution is 0.5-5 mg / ml; the concentration of the inner layer polyphenol solution is 0.02-2 mg / ml; the concentration of ethanol is 10%; and the inner layer protein solution and the inner layer polyphenol solution are mixed at a volume ratio of 1:1.

[0007] Furthermore, the concentration of the outer polyphenol solution is 0.02-2 mg / ml; the concentration of the outer protein solution is 0.5-5 mg / ml; the concentration of the metal ion solution is 0.1-1 mg / ml; and the outer protein solution, the outer polyphenol solution, and the metal ion solution are mixed in a volume ratio of 1:1:1.

[0008] Furthermore, when the pretreated substrate is irradiated with the inner coating mixture solution, the wavelength of the ultraviolet lamp is 365 nm and the wavelength is 15 mW / cm. 2 Irradiate for 30-60 minutes.

[0009] Furthermore, when the modified matrix is ​​irradiated with the outer coating mixture solution, the wavelength of the ultraviolet lamp is 365 nm, and the wavelength is 12-20 mW / cm. 2 Irradiate for 1-60 minutes.

[0010] Furthermore, the matrix comprises silicone hydrogel or polyhydroxyethyl methacrylate.

[0011] Furthermore, the inner layer protein solution includes lysozyme, tyrosinase, or peroxidase; The inner polyphenol solution includes quercetin, baicalin, curcumin, or resveratrol; The outer protein solution includes bovine serum albumin, human albumin, equine albumin, sheep albumin, or rabbit albumin. The outer polyphenol solution includes epigallocatechin gallate, tannic acid, or proanthocyanidins; The metal ion solution includes silver ions, zinc ions, copper ions, or cerium ions.

[0012] In a second aspect, an anti-inflammatory and anti-protein adhesion metal polyphenol protein bilayer coating is provided, wherein the metal polyphenol protein bilayer coating is prepared by the method described in the first aspect above.

[0013] Thirdly, a medical device is provided, the medical device comprising the metal polyphenol protein double coating described in the first aspect above.

[0014] Fourthly, a contact lens is provided, the lens comprising the metal polyphenol protein double coating described in the first aspect above.

[0015] The beneficial effects of the technical solution provided in this application are as follows: The preparation method of the anti-inflammatory and anti-protein adhesion metal polyphenol protein bilayer coating of this application includes the following steps: preparing an inner layer protein solution with deionized water, preparing an inner layer polyphenol solution with ethanol, and then mixing the inner layer protein solution and the inner layer polyphenol solution to obtain an inner layer coating mixture solution; preparing an outer layer protein solution, an outer layer polyphenol solution and a metal ion solution with deionized water respectively, and then mixing the outer layer protein solution, the outer layer polyphenol solution and the metal ion solution to obtain an outer layer coating mixture solution; completely immersing the pretreated substrate in the inner layer coating mixture solution and irradiating it with an ultraviolet lamp to obtain a modified substrate; placing the modified substrate in the outer layer coating mixture solution and continuing to irradiate it with an ultraviolet lamp to obtain the metal polyphenol protein bilayer coating. This application utilizes the outer layer (epigallocatechin gallate + bovine serum albumin + cerium ions) as the first line of defense to exert rapid antibacterial, anti-inflammatory and anti-tear protein deposition effects, and utilizes the inner layer (catalase + quercetin) as the long-term defense to exert deep ROS scavenging, oxygen production and energy supply and sustained anti-inflammatory effects. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 These are macroscopic images of the contact lenses of each modified group in Example 4 of this application, and their light transmittance in an aquatic environment. Figure 2 These are fluorescence micrographs of macrophages cultured on different surfaces in Example 4 of this application; Figure 3 This is a graph showing the quantitative analysis results of the proliferation activity of macrophages after culturing on different surfaces in Example 4 of this application; Figure 4 These are fluorescence micrographs of human corneal epithelial cells cultured on different surfaces in Example 4 of this application; Figure 5 This is a diagram showing the quantitative analysis results of the proliferation activity of human corneal epithelial cells after culturing on different surfaces in Example 4 of this application; Figure 6 This is a graph showing the effect of different modified coatings on the transmittance of 365 nm and 254 nm ultraviolet light in Example 4 of this application. Figure 7 This is a graph showing the total antioxidant capacity of different modified coatings in Example 4 of this application. Detailed Implementation

[0018] To make the objectives, technical solutions, and advantages of this application clearer, the embodiments of this application will be described in further detail below with reference to the accompanying drawings.

[0019] It should be understood that the described embodiments are merely some, not all, of the embodiments in this application. All other embodiments obtained by those skilled in the art based on the embodiments in this application without inventive effort are within the scope of protection of this application.

[0020] In the following description, when referring to the accompanying drawings, the same numbers in different drawings denote the same or similar elements unless otherwise indicated. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with this application. Rather, they are merely examples of apparatuses and methods consistent with some aspects of this application as detailed in the appended claims.

[0021] In the description of this application, it should be understood that the terms "first," "second," "third," etc., are used only to distinguish similar objects and are not necessarily used to describe a specific order or sequence, nor should they be construed as indicating or implying relative importance. In the description of this application, unless otherwise stated, "multiple" means two or more. Example 1

[0022] (1) Matrix pretreatment First, place the contact lens substrate (such as silicone hydrogel or polyhydroxyethyl methacrylate substrate) in deionized water and ultrasonically clean it for 3 minutes to remove residual monomers and impurities on the surface.

[0023] (2) Inner layer CAT+QE composite coating Prepare a CAT (catalase) solution with a concentration of 0.5 mg / ml using deionized water, and a QE (quercetin) solution with a concentration of 0.02 mg / ml using 10% ethanol. Then, mix the CAT solution and QE solution at a volume ratio of 1:1 to obtain the inner coating mixture solution.

[0024] The pretreated contact lens substrate was completely immersed in the above-mentioned inner coating mixture solution. The immersed or removed lenses were then irradiated with a 365nm ultraviolet lamp at a wavelength of 15 mW / cm². 2 After irradiation for 60 minutes, a modified contact lens substrate was obtained. Through UV energy-induced oxidative polymerization of QE molecules and covalent cross-linking between CAT molecular chains, a dense CAT+QE inner coating with high antioxidant activity was formed on the substrate surface.

[0025] (3) Outer EGCG+BSA composite coating A solution of EGCG (epigallocatechin gallate) with a concentration of 0.02 mg / ml, a solution of BSA (bovine serum albumin) with a concentration of 0.5 mg / ml, and a solution of cerium acetate with a concentration of 0.01 mg / ml were prepared using deionized water. The EGCG solution, BSA solution, and cerium acetate solution were then mixed in a volume ratio of 1:1:1 to obtain the outer coating mixture solution.

[0026] The modified contact lens matrix was placed in an outer coating mixture solution, and the immersed or removed lenses were irradiated with a 365nm ultraviolet lamp at 12 mW / cm². 2 Irradiation for 60 minutes yielded a contact lens matrix with a metal polyphenol protein bilayer coating possessing anti-inflammatory and anti-protein adhesion properties. Using BSA as a natural carrier protein, it pre-binded with the plant polyphenol EGCG through hydrophobic interactions and hydrogen bonds, and the polyphenol's metal coordination ability bound to cerium ions, forming a stable precursor solution. Example 2

[0027] (1) Matrix pretreatment First, the vascular stent substrate (316L or nickel-titanium alloy) is placed in deionized water and ultrasonically cleaned for 4 minutes to remove residual monomers and impurities on the surface.

[0028] (2) Inner layer lysozyme + baicalin composite coating Prepare a lysozyme solution with a concentration of 3 mg / ml using deionized water, and prepare a baicalin solution with a concentration of 1 mg / ml using 10% ethanol. Then mix the lysozyme solution and the baicalin solution at a volume ratio of 1:1 to obtain the inner coating mixture solution.

[0029] The pretreated contact lens substrate was completely immersed in the above-mentioned inner coating mixture solution. The immersed or removed lenses were then irradiated with a 254nm ultraviolet lamp at a wavelength of 15 mW / cm². 2 After irradiation for 45 minutes, a modified contact lens matrix was obtained. Through UV energy-induced oxidative polymerization of baicalin molecules and covalent cross-linking between lysozyme molecular chains, a tight, highly antioxidant lysozyme + baicalin inner coating was formed on the matrix surface.

[0030] (3) Outer tannic acid + HAS composite coating A tannic acid solution with a concentration of 1 mg / ml, a HAS (human albumin) solution with a concentration of 2.5 mg / ml, and a silver ion solution with a concentration of 0.5 mg / ml were prepared using deionized water. The tannic acid solution, HAS solution, and cerium ion solution were then mixed in a volume ratio of 1:1:1 to obtain the outer coating mixture solution.

[0031] The modified contact lens matrix was placed in an outer coating mixture solution, and the immersed or removed lenses were irradiated with a 365nm ultraviolet lamp at 16 mW / cm². 2 Irradiation for 30 minutes yielded a contact lens matrix with a metal polyphenol protein double-layer coating possessing anti-inflammatory and anti-protein adhesion properties. Utilizing HAS as a natural carrier protein, it pre-binded with plant polyphenol tannins through hydrophobic interactions and hydrogen bonds, and the metal coordination ability of polyphenols bound to silver ions, forming a stable precursor solution. Example 3

[0032] (1) Matrix pretreatment First, the contact lens matrix (polyhydroxyethyl methacrylate matrix) is placed in deionized water and ultrasonically cleaned for 5 minutes to remove residual monomers and impurities on the surface.

[0033] (2) Inner layer tyrosinase + resveratrol composite coating Prepare a tyrosinase solution with a concentration of 5 mg / ml using deionized water, and prepare a resveratrol solution with a concentration of 2 mg / ml using 10% ethanol. Then, mix the tyrosinase solution and the resveratrol solution at a volume ratio of 1:1 to obtain the inner coating mixture solution.

[0034] The pretreated contact lens substrate was completely immersed in the above-mentioned inner coating mixture solution. The immersed or removed lenses were then irradiated with a 365nm ultraviolet lamp at a wavelength of 15 mW / cm². 2 After irradiation for 30 minutes, a modified contact lens substrate was obtained. Through UV energy-induced oxidative polymerization of resveratrol molecules and covalent cross-linking between tyrosinase molecular chains, a tight, highly antioxidant tyrosinase + resveratrol inner coating was formed on the substrate surface.

[0035] (3) Outer layer proanthocyanidin + BSA composite coating A 2 mg / ml proanthocyanidin solution, a 5 mg / ml BSA solution, and a 1 mg / ml cerium ion solution were prepared using deionized water. The proanthocyanidin solution, BSA solution, and zinc ion solution were then mixed in a volume ratio of 1:1:1 to obtain the outer coating mixture solution.

[0036] The modified contact lens matrix was placed in an outer coating mixture solution, and the immersed or removed lenses were irradiated with a 365nm ultraviolet lamp at a wavelength of 20 mW / cm². 2 Irradiation for 1 minute yielded a contact lens matrix with a metal polyphenol protein bilayer coating possessing anti-inflammatory and anti-protein adhesion properties. Using BSA as a natural carrier protein, it pre-binded with plant polyphenol proanthocyanidins through hydrophobic interactions and hydrogen bonds, and the metal coordination ability of polyphenols bound to zinc ions, forming a stable precursor solution. Example 4

[0037] The effects of unmodified contact lenses (uncoated, Con), lysozyme + quercetin coated contact lenses (LZM+QE), lysozyme + quercetin-epigallocatechin gallate + bovine serum albumin + cerium ion coated contact lenses (LZM+QE-EGCG+BAS+Ce), catalase + quercetin coated contact lenses (CAT+QE), and the metal polyphenol protein double-coated contact lenses prepared in Example 1 (CAT+QE-EGCG+BAS+Ce) on the macroscopic physical and optical properties of contact lenses were preliminarily evaluated.

[0038] (1) Observation of physical morphology and underwater light transmittance test The physical morphology of each modified sample was observed and its underwater transmittance was tested. For example... Figure 1 As shown in (a), all contact lens samples maintained good integrity and their original hemispherical curved surface structure in terms of macroscopic morphology. For contact lenses that come into contact with the eyeball, maintaining excellent light transmission performance is a prerequisite for their clinical application. Figure 1 (b) shows the light transmission effect when each group of contact lens samples is immersed in an aqueous solution and placed above a colored text background. It can be clearly observed that the boundaries of the colored blocks at the bottom remain clear when viewed through all the modified contact lens samples.

[0039] (2) Cytotoxicity test Macrophages were diluted to 20,000 Cell / mL with a specific culture medium and added to sterile 24-well plates. These plates were then co-cultured with the Con / CAT+QE-EGCG+BAS+Ce contact lens samples for 24 h. After culturing, the Con / CAT+QE-EGCG+BAS+Ce contact lens samples were transferred to new 24-well plates, PBS was added to wash away any unattached cells, and cultured with 10% CCK-8 cell culture medium for 1 h. The absorbance was measured using a microplate reader at 450 nm.

[0040] like Figure 2 As shown, after culturing the contact lens samples for a certain period of time, the macrophages exhibited a clear and bright green fluorescent signal. Most macrophages were normal round or oval in shape, relatively uniformly distributed, and no obvious cell debris or large-area cell shrinkage, lysis, or other signs of apoptosis were observed. This clearly demonstrates that the composite modified coating did not produce any adverse physical or chemical stimulation to the adhesion and survival of macrophages.

[0041] To further quantify the cytotoxicity of the coating, the metabolic and proliferative activity of macrophages was detected using the CCK-8 assay. The results are as follows: Figure 3The modified contact lens sample (CAT+QE-EGCG+BAS+Ce) showed no obvious inflammation.

[0042] Human corneal epithelial cells were diluted to 40,000 Cell / mL with a specific culture medium and added to sterile 24-well plates. These plates were then co-cultured with Con / CAT+QE-EGCG+BAS+Ce contact lens samples for 24 h. After culturing, the Con / CAT+QE-EGCG+BAS+Ce contact lens samples were transferred to new 24-well plates, PBS was added to wash away any unattached cells, and culture medium containing 10% CCK-8 cells was added. The plates were then co-cultured for 1 h, and absorbance was measured at 450 nm using a microplate reader.

[0043] Combination Figure 4 and Figure 5 It can be seen that the modified contact lens sample (CAT+QE-EGCG+BAS+Ce) has no obvious toxicity to human corneal epithelial cells and shows a trend of promoting the growth of human corneal epithelial cells.

[0044] (3) Ultraviolet light blocking rate of each modified contact lens sample Each group of contact lens samples was placed in ultraviolet light environments of two wavelengths, 265 nm and 365 nm, and the ultraviolet intensity of each sample was measured using an ultraviolet light intensity meter. Three parallel samples were set up for each group.

[0045] The results are as follows Figure 6 As shown, compared with the completely transparent Con sample group, each modified group showed a certain UV blocking effect, demonstrating basic UVA protection capability.

[0046] Under the more destructive high-energy 254 nm ultraviolet light, the coating exhibited extremely excellent shielding effect. Although LZM+QE or CAT+QE can only reduce transmittance by 70%-80%, the transmittance of the modified coating contact lens sample after secondary modification with the addition of metallic cerium showed a precipitous drop.

[0047] (4) Coating oxidation resistance The total antioxidant capacity of different modified coatings was tested using the ABTS rapid method.

[0048] Each group of samples was placed in a 24-well plate, working solution was added, and incubated at room temperature in the dark for 6 min. The absorbance was measured at 425 nm using a microplate reader. The ABTS radical concentration was calculated based on the standard curve. Three replicates were set up for each sample group. The lighter the blue-green color of the solution and the lower the absorbance, the stronger the radical scavenging ability of the coating. The results are as follows: Figure 7 As shown.

[0049] The residual free radical level in the untreated Con sample group was set at 100%. Observation of the modified groups revealed that the LZM+QE sample group showed almost no significant decrease, while the CAT+QE sample group's level dropped to approximately 70%. This difference is mainly attributed to the biological enzymatic activity of catalase (CAT), which specifically catalyzes the decomposition of peroxides in the system, thus exhibiting a certain basic antioxidant performance. When a secondary grafting was performed on the coating surface to introduce the EGCG+BSA+Ce composite system, the antioxidant performance changed significantly. The residual free radical level plummeted to 20%. Statistical analysis confirmed that the improvement in antioxidant capacity of the secondary modification group compared to their respective base coatings was statistically highly significant.

[0050] In the anti-inflammatory and anti-protein adhesion metal polyphenol protein bilayer coating of this application, CAT, as the biocatalytic core, can precisely degrade ultraviolet-induced hydrogen peroxide; simultaneously, combined with the multi-hydroxyl structure of QE and EGCG, it forms a strong reducing protective barrier. This combined design of "enzyme + antioxidant small molecule" solves the problem that traditional lenses cannot remove superoxide anions and hydroxyl radicals, effectively preventing lens material aging and yellowing. Using BSA as the film-forming framework solves the existing technical problems of natural active ingredients being easily washed away by tears and having poor stability. BSA not only fixes antioxidant molecules through hydrogen bonds and hydrophobic interactions, but also acts as a sacrificial buffer for secondary antioxidant effects, ensuring the long-lasting anti-ultraviolet and antioxidant functions throughout the entire wearing period. Cerium ions are grafted onto the surface of the polyphenol protein coating. Cerium ions have certain antibacterial efficacy and reduce the reaction sites on the surface of the polyphenol protein coating, thereby reducing the adsorption of the main protein (lysozyme) in tears.

[0051] The cascade reaction mechanism for scavenging reactive oxygen species (ROS): During keratitis, the affected area is often accompanied by severe oxidative stress. CAT in the coating, as a natural and highly effective antioxidant enzyme, can catalyze the rapid decomposition of peroxides accumulated in corneal secretions and the inflammatory environment into water and oxygen. The generated oxygen not only improves the local hypoxic state of the cornea and assists in the repair of damaged epithelial cells, but also fine-tunes the coating's permeability through physical pressure.

[0052] Synergistic Anti-inflammatory and Antibacterial Effects of Polyphenols: QE and EGCG, as plant-derived polyphenols, possess extremely strong free radical scavenging capabilities and broad-spectrum antibacterial activity. EGCG exerts its bactericidal effect by disrupting the integrity of bacterial cell membranes and inhibiting the activity of related enzymes; QE, on the other hand, blocks the inflammatory cascade by downregulating the expression of inflammatory factors (such as IL-1β and TNF-α). Both are stably encapsulated in a coating mesh through hydrophobic interactions and hydrogen bonding with BSA, achieving sustained release.

[0053] It is not a simple mechanical superposition, but a complex bioactive system formed by layered construction. Its structure can be precisely disassembled from the inside out into four core dimensions: a base support layer, a protein backbone binding layer, an active drug delivery matrix, and an enzyme-catalyzed defense surface layer.

[0054] The base layer, serving as the structural support, utilizes a medical-grade hydrogel substrate. In-situ crosslinking technology induced by ultraviolet (UV) irradiation is employed to divide the coating into a functionally distinct bilayer structure. The inner layer (active catalytic and antioxidant core layer) consists of catalase (CAT) and quercetin (QE), which are tightly bound to the activated substrate surface through UV-induced free radical polymerization or photocrosslinking reactions. Immediately following the inner layer is the outer layer (biological barrier and sustained-release protective layer), synergistically composed of epidermal gallate-catechin gallate (EGCG) and bovine serum albumin (BSA). In this structure, BSA acts as a macromolecular biological scaffold; its molecular chains undergo photocrosslinking under UV irradiation, forming a dense protein mesh. EGCG, on the other hand, is superimposed within the hydrophobic pockets and mesh pores of BSA through strong stacking interactions and multiple hydrogen bonds. This interpenetrating network (IPN) between the outer and inner layers, achieved through a layered UV irradiation process, ensures that the bilayer structure does not delaminate. Located on the outer layer, EGCG-BSA not only exerts its broad-spectrum antibacterial activity, inhibiting the adhesion of pathogens to the lens surface, but also provides slow-release protection, preventing the instantaneous release of CAT and QE in the inner layer during the initial wearing period.

[0055] The above are merely preferred embodiments of this application and are not intended to limit the scope of this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of the claims of this application.

Claims

1. A method for preparing a metal polyphenol protein bilayer coating with anti-inflammatory and anti-protein adhesion properties, characterized in that, Includes the following steps: An inner layer protein solution is prepared using deionized water, and an inner layer polyphenol solution is prepared using ethanol. The inner layer protein solution and the inner layer polyphenol solution are then mixed to obtain an inner layer coating mixture solution. An outer layer protein solution, an outer layer polyphenol solution, and a metal ion solution were prepared using deionized water. Then, the outer layer protein solution, the outer layer polyphenol solution, and the metal ion solution were mixed to obtain an outer coating mixture solution. The pretreated substrate was completely immersed in the inner coating mixture solution and irradiated with an ultraviolet lamp to obtain the modified substrate; The modified matrix is ​​placed in the outer coating mixture solution and irradiated with an ultraviolet lamp to obtain the metal polyphenol protein bilayer coating.

2. The method according to claim 1, characterized in that, The concentration of the inner layer protein solution is 0.5-5 mg / ml; the concentration of the inner layer polyphenol solution is 0.02-2 mg / ml; the concentration of ethanol is 10%; the inner layer protein solution and the inner layer polyphenol solution are mixed at a volume ratio of 1:

1.

3. The method according to claim 1, characterized in that, The concentration of the outer polyphenol solution is 0.02-2 mg / ml; the concentration of the outer protein solution is 0.5-5 mg / ml; the concentration of the metal ion solution is 0.1-1 mg / ml; the outer protein solution, the outer polyphenol solution, and the metal ion solution are mixed in a volume ratio of 1:1:

1.

4. The method according to claim 1, characterized in that, When the pretreated substrate is irradiated with the inner coating mixture solution, the wavelength of the ultraviolet lamp is 365 nm and the wavelength is 15 mW / cm. 2 Irradiate for 30-60 minutes.

5. The method according to claim 1, characterized in that, When the modified matrix is ​​irradiated with the outer coating mixture solution, the wavelength of the ultraviolet lamp is 365 nm, and the wavelength is 12-20 mW / cm. 2 Irradiate for 1-60 minutes.

6. The method according to claim 1, characterized in that, The matrix includes silicone hydrogel or polyhydroxyethyl methacrylate.

7. The method according to claim 1, characterized in that, The inner protein solution includes lysozyme, tyrosinase, or peroxidase. The inner polyphenol solution includes quercetin, baicalin, curcumin, or resveratrol; The outer protein solution includes bovine serum albumin, human albumin, equine albumin, sheep albumin, or rabbit albumin. The outer polyphenol solution includes epigallocatechin gallate, tannic acid, or proanthocyanidins; The metal ion solution includes silver ions, zinc ions, copper ions, or cerium ions.

8. A metal polyphenol protein bilayer coating with anti-inflammatory and anti-protein adhesion properties, characterized in that, The metal polyphenol protein bilayer coating is prepared by the method of claims 1-7.

9. A medical device, characterized in that, The medical device includes the metal polyphenol protein double coating as described in claim 8.

10. A contact lens, characterized in that, The lens comprises the metal polyphenol protein double coating as described in claim 8.

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