Wet response polyglutamic acid hydrogel coating as well as preparation method and application thereof

Abstract

The invention discloses a wet response polyglutamic acid hydrogel coating as well as a preparation method and application thereof, and belongs to the technical field of medical coating materials. The wet response polyglutamic acid hydrogel coating is formed by interpenetrating and connecting a bottom-layer network structure and a top-layer network structure; the bottom-layer network structure is obtained by a coupling reaction of a hydroxyl-containing substrate and a hydrophilic-hydrophobic copolymer containing a silane coupling unit; the top-layer network structure is obtained by carrying out amidation reaction on gamma-polyglutamic acid modified by N-hydroxysuccinimide and a multi-amino polymer. The wet response polyglutamic acid hydrogel coating has the double functions of lubricity and antibacterial property, also has good biocompatibility and interface adhesion, and is stronger and more stable in adhesive force with a base material in a wet environment; the problems that an existing medical coating is single in function, depends on a base material, is weak in adhesion with the base material in a wet environment and is poor in stability are solved, and the medical coating has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of medical coating materials, and in particular to a wet-state responsive polyglutamic acid hydrogel coating and a preparation method and application thereof. Background Art

[0002] Implantable medical devices such as urinary catheters and intravenous catheters are widely used in clinical practice. With the aging of the population, the demand for implantable medical devices is increasing. However, during the implantation process, the excessive friction on the surface of medical devices can cause difficulties in intervention and cause discomfort and pain to patients. There is also the risk of bacteria adhering to and proliferating on the surface of the device, and even forming a biofilm, which can eventually lead to bacterial infection and related complications.

[0003] At present, constructing an antifouling coating with both lubrication and antibacterial functions on the surface of medical devices is an effective way to solve the above problems. In recent years, hydrogel coatings have gained widespread attention due to their excellent hydrophilicity and softness. It is a simple and easy method to achieve lubrication on the surface of medical devices by forming a stable hydration layer on the surface of the hydrogel coating. Lubricating hydrogel coatings can form a hydration layer barrier in a physiological wet environment, which acts as a physical barrier to resist the adhesion of microorganisms such as bacteria. However, this type of coating surface can only block the adhesion of bacteria. After the bacteria attach, they will still proliferate on its surface and even form a biofilm.

[0004] In addition, the current hydrogel coating is constructed in a single way and is substrate-dependent, and its mechanical strength and adhesion to the interface with the substrate material are also weak, and its stability in a wet environment is also poor. These problems severely limit the application of hydrogel coatings in implantable medical devices.

[0005] Therefore, it is urgent to develop a medical coating material that has lubricity and antibacterial properties in a physiological wet environment, and has strong adhesion and high stability at the substrate interface. Summary of the invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide a wet-responsive polyglutamic acid hydrogel coating and a preparation method and application thereof. The hydrogel coating has good antibacterial properties, mechanical properties, excellent interface adhesion properties and good lubrication effect.

[0007] In order to achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] The present invention provides a wet-state responsive polyglutamic acid hydrogel coating composed of a bottom network structure and a top network structure interpenetratingly connected;

[0009] The bottom layer network structure is obtained by coupling reaction between a hydroxyl-containing substrate and a hydrophilic-hydrophobic copolymer containing a silane coupling unit;

[0010] The top layer network structure is obtained by amidation reaction of gamma-polyglutamic acid modified by N-hydroxysuccinimide and polyamino polymer.

[0011] In the above-mentioned wet-responsive polyglutamic acid hydrogel coating, the top network structure has strong hydrophilicity, can quickly form a lubricating hydration layer in a wet state, and has excellent anti-bacterial adhesion and antibacterial properties. This is because the top network structure contains a large number of hydrophilic groups, which can quickly form a hydration layer in a wet environment and increase the lubricity of the coating surface. The bottom network structure can trigger microphase separation in a wet state, thereby enhancing the interaction between the coating and the substrate, so as to improve the stability of the interface between the coating and the medical substrate in a wet environment.

[0012] Preferably, the hydrophilic-hydrophobic copolymer containing silane coupling units is prepared by free radical polymerization of a silane coupling agent, acetic acid, a chain transfer agent, a vinyl monomer and a photoinitiator;

[0013] Preferably, the silane coupling agent contains a vinyl group;

[0014] Preferably, the vinyl monomer is selected from a mixture of a hydrophilic vinyl monomer and a hydrophobic vinyl monomer;

[0015] Preferably, the photoinitiator is selected from cleavage-type photoinitiators.

[0016] Preferably, the molar ratio of the silane coupling agent to the vinyl monomer is (0.00001-1):1, and more preferably (0.00002-1):1. In some specific embodiments of the present invention, the molar ratio of the silane coupling agent to the vinyl monomer is 0.000015:1 or 0.00001:1.

[0017] Preferably, the molar ratio of the hydrophilic vinyl monomer to the hydrophobic vinyl monomer in the vinyl monomer is (0.1-10):1, more preferably (0.1-2):1. In some specific embodiments of the present invention, it is preferably 1:1.

[0018] The molar concentration of the photoinitiator is preferably 0.02-2 mol / L, more preferably 0.05-0.5 mol / L; further preferably 0.1 mol / L. Preferably, the silane coupling agent is selected from vinyl trimethoxysilane, vinyl triethoxysilane or 3-(trimethoxysilyl) propyl methacrylate (TMSPMA);

[0019] Preferably, the hydrophilic vinyl monomer is selected from one or more of acrylic acid, hydroxyethyl acrylate, dimethylaminoethyl acrylate, methacrylic acid, hydroxyethyl methacrylate, dimethylaminoethyl methacrylate, and poly(ethylene glycol) methacrylate; more preferably, hydroxyethyl acrylate (HEA) or methacrylic acid; and further preferably, hydroxyethyl acrylate (HEA).

[0020] Preferably, the hydrophobic vinyl monomer is selected from one or more of butyl acrylate, 2-ethylhexyl acrylate, benzyl acrylate, butyl methacrylate, 2-ethylhexyl methacrylate, and benzyl methacrylate; more preferably, 2-ethylhexyl acrylate (2-EHA) or benzyl methacrylate (BzMA).

[0021] Further preferably, the vinyl monomer is selected from a mixture of HEA and 2-EHA, or the vinyl monomer is selected from a mixture of HEA and BzMA.

[0022] Preferably, the cleavage-type photoinitiator is selected from α-hydroxyketone derivative photoinitiator Irgacure 2959, photoinitiator 1173 or phosphonyl initiator LAP.

[0023] Preferably, the hydroxyl-containing substrate is obtained by surface hydroxylation of elastomer, plastic, glass, ceramic or metal.

[0024] The surface hydroxylation treatment includes but is not limited to oxygen plasma treatment and ozone ultraviolet treatment.

[0025] The surface hydroxylation treatment time is preferably 1-60 min, more preferably 3-10 min. The elastomer includes but is not limited to polyurethane (PU), silicone rubber, polyvinyl chloride (PVC), thermoplastic elastomer (TPE) and the like.

[0026] Preferably, the polyamino polymer is selected from one or more of polylysine, polyethyleneimine, polyhexamethyleneguanidine hydrochloride, and polyhexamethylenemonoguanidine hydrochloride.

[0027] The present invention also provides a method for preparing the above-mentioned wet-state responsive polyglutamic acid hydrogel coating, comprising the following steps:

[0028] (1) coating a hydrophilic-hydrophobic copolymer containing a silane coupling unit on the surface of a hydroxyl-containing substrate and curing the coating to obtain the underlying network structure;

[0029] (2) Mixing and reacting N-hydroxysuccinimide-modified γ-polyglutamic acid and a polyamino polymer in an alkaline environment and coating the mixture on the surface of the underlying network structure to obtain the wet-state responsive polyglutamic acid hydrogel coating.

[0030] Preferably, the curing method in step (1) is ultraviolet light curing;

[0031] Preferably, the temperature of the UV curing is 25°C-100°C; more preferably 40°C-70°C. Preferably, the UV curing intensity is 10-2000 mw / cm 2 ; More preferably 100-2000mw / cm 2 Preferably, the ultraviolet light irradiation time of the ultraviolet light curing is 5-60 minutes; more preferably, 10-30 minutes.

[0032] Preferably, in the present invention, the molar ratio of the N-hydroxysuccinimide-modified γ-polyglutamic acid to the polyamino polymer is 1:(0.01-1).

[0033] The alkaline environment in step (2) is provided by sodium bicarbonate, potassium carbonate, tris buffer, etc.

[0034] The preparation method described in the present invention first couples a hydrophilic and hydrophobic copolymer containing a silane coupling unit with a hydroxyl-containing substrate surface to form a covalently interconnected underlying network structure (also called a first network structure). This method only requires a simple treatment of the surface of the substrate material to give it a hydroxyl group, is not substrate-dependent, and is suitable for various medical device materials.

[0035] Then, the top network structure (also called the second network structure) is coated on the surface of the bottom network structure to form a wet-state responsive polyglutamic acid hydrogel coating with a double-layer network structure.

[0036] The wet-responsive polyglutamic acid hydrogel coating with a double-layer network structure has good antibacterial properties, mechanical properties, excellent interface adhesion properties and good lubrication effect through the combined effect of the bottom layer and the top layer network structure, thereby solving the problems of existing medical coatings that they have a single function, are dependent on the substrate, have weak adhesion to the substrate in a wet environment, and have poor stability.

[0037] In the present invention, preferably, the above preparation method comprises the following steps:

[0038] 1) adding a silane coupling agent, acetic acid and a chain transfer agent to a solution containing a hydrophilic vinyl monomer and a hydrophobic vinyl monomer, and then adding a photoinitiator and mixing evenly to obtain a mixed solution S1;

[0039] 2) sealing the mixed solution S1 of step 1) and irradiating it under ultraviolet light, and initiating free radical polymerization of the hydrophilic vinyl monomer and the hydrophobic vinyl monomer by light to obtain a hydrophilic and hydrophobic copolymer containing a silane coupling unit, coating the copolymer on the surface of the substrate after surface hydroxylation treatment, and heating and curing the copolymer to obtain an underlying network structure;

[0040] 3) After dissolving γ-polyglutamic acid (γ-PGA) in anhydrous DMSO, N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) were added, and the mixture was stirred at room temperature for 12 hours under nitrogen protection. The precipitate was washed three times with ethanol, acetone and n-hexane, respectively, and vacuum dried to obtain NHS-modified γ-polyglutamic acid (γ-PGA-NHS), and then γ-PGA-NHS was dissolved in an alkaline solution and mixed with an equal volume of polyamino polymer to obtain a mixed solution S2;

[0041] 4) coating the mixed solution S2 on the surface of the bottom network structure obtained in step 2) to obtain the wet-responsive polyglutamic acid hydrogel coating of the present invention, which consists of a bottom network structure and a top network structure, wherein the top network structure is a network structure formed by an amidation product of the reaction of γ-PGA-NHS and a polyamino polymer.

[0042] The mixing in step 1) can be carried out using a vortex mixer for 15 seconds.

[0043] The substrate after the surface hydroxylation treatment in step 2) further includes a pretreatment before the surface hydroxylation treatment.

[0044] The pretreatment includes processes such as rinsing with deionized water and drying with nitrogen.

[0045] The γ-polyglutamic acid in step 3) is obtained by a biological fermentation method, and its molecular weight range is 10-200W, preferably 50-200W;

[0046] The mass ratio of N-hydroxysuccinimide to γ-polyglutamic acid in step 3) is (0.05-1):1; preferably (0.5-1):1;

[0047] The mass ratio of N-hydroxysuccinimide to EDC in step 3) is (0.1-5):1; preferably (0.5-1.2):1.

[0048] The concentration of γ-PGA-NHS in the sodium bicarbonate solution in step 3) is preferably 1-20 wt %; more preferably 5-10 wt %.

[0049] The present invention also provides the use of the above-mentioned wet-state responsive polyglutamic acid hydrogel coating or the wet-state responsive polyglutamic acid hydrogel coating prepared by the above-mentioned preparation method in implantable medical devices, wound care or tissue engineering.

[0050] Compared with the prior art, the wet-state responsive polyglutamic acid hydrogel coating provided by the present invention is composed of a bottom network structure and a top network structure interpenetrating each other; the bottom network structure is obtained by coupling reaction between a hydroxyl-containing substrate and a hydrophilic-hydrophobic copolymer containing a silane coupling unit; the top network structure is obtained by amidation reaction between γ-polyglutamic acid modified by N-hydroxysuccinimide and a polyamino polymer. The wet-state responsive polyglutamic acid hydrogel coating has both lubricity and antibacterial properties, good biocompatibility and interfacial adhesion, and has stronger and more stable adhesion to the substrate in a wet environment, which solves the problems of the existing medical coatings being single in function, dependent on the substrate, weak adhesion to the substrate in a wet environment, and poor stability, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 Schematic diagram of the construction of the wet-state responsive polyglutamic acid hydrogel coating of the present invention;

[0052] Figure 2 Antibacterial test diagram of the coating materials prepared in Examples 1-2 and Comparative Examples 2-4 and the polyurethane substrate of Comparative Example 1;

[0053] Figure 3 This is a test diagram of the adhesion performance between the coating material and the substrate material prepared in Examples 1-2 and Comparative Examples 2-4;

[0054] Figure 4 Friction performance test diagram of the coating materials prepared in Examples 1-2 and Comparative Examples 2-4 and the polyurethane substrate of Comparative Example 1. DETAILED DESCRIPTION

[0055] To further illustrate the present invention, the wet-state responsive polyglutamic acid hydrogel coating provided by the present invention and its preparation method and application are described in detail below in conjunction with the embodiments.

[0056] Example 1

[0057] To a mixed solution of hydroxyethyl acrylate (HEA) and 2-ethylhexyl acrylate (2-EHA) (2 mol / L, where the molar ratio of HEA to 2-EHA is 1:1), 3.7 μL of silane coupling agent TMSPMA, 10 μL of chain transfer agent CTA (1% V / V), and then 0.1 mol / L of photoinitiator L2959 were added, and a vortex mixer (2500 rpm) was used for 15 s to fully mix. The precursor was then sealed in a syringe and exposed to ultraviolet light (1200 mw / cm 2 ) was irradiated for 30 min to obtain a hydrophilic-hydrophobic copolymer p(HEA-co-EHA-co-TMSPMA) containing a silane coupling unit.

[0058] After dissolving γ-polyglutamic acid (γ-PGA) with a molecular weight of 200w Da in anhydrous DMSO, 0.9g NHS and 1.48g EDC were added and stirred at room temperature for 12h under nitrogen atmosphere. Subsequently, the mixture was precipitated in ethanol / methanol (v / v=3 / 1), and the precipitate was washed three times with ethanol, acetone and n-hexane respectively. γ-PGA-NHS was obtained by vacuum drying.

[0059] The polyurethane film substrate was ultrasonically cleaned 3 times with anhydrous ethanol, then rinsed with ionized water 3 times, and after complete drying, the surface of the material was activated for 3 minutes using a plasma processor to obtain a hydroxyl-containing polyurethane film substrate. A hydrophilic and hydrophobic copolymer containing a silane coupling unit (10 μL was added, and 0.1 mol / L acetic acid was used to adjust the pH) was applied to the activated (hydroxyl-containing) polyurethane surface and cured in a 65°C oven for 24 hours. Subsequently, 10wt% γ-PGA-NHS was dissolved in sodium bicarbonate, mixed with an equal volume of 10wt% polylysine (PL) aqueous solution, and applied to the upper surface of the coating to obtain a hydrogel coating with a double-layer network structure.

[0060] Example 2

[0061] To a mixed solution of HEA and benzyl methacrylate (BzMA) (2 mol / L, where the molar ratio of HEA to BzMA is 1:1), 1.9 μL of silane coupling agent TMSPMA, 10 μL of chain transfer agent CTA (1% V / V), and then 0.1 mol / L of photoinitiator L2959 were added, and a vortex mixer (2500 rpm) was used for 15 s to fully mix. The precursor was then sealed in a syringe and exposed to ultraviolet light (1200 mw / cm 2 ) was irradiated for 30 min to obtain a hydrophilic-hydrophobic copolymer p(HEA-co-BzMA-co-TMSPMA) containing a silane coupling unit.

[0062] After dissolving γ-polyglutamic acid (γ-PGA) with a molecular weight of 200w Da in anhydrous DMSO, 0.9g NHS and 1.48g EDC were added and stirred at room temperature for 12h under nitrogen atmosphere. Subsequently, the mixture was precipitated in ethanol / methanol (v / v=3 / 1), and the precipitate was washed three times with ethanol, acetone and n-hexane respectively. γ-PGA-NHS was obtained by vacuum drying.

[0063] The polyurethane film substrate was ultrasonically cleaned 3 times with anhydrous ethanol, then rinsed with ionized water 3 times, and after complete drying, the surface of the material was activated for 3 minutes using a plasma processor to obtain a hydroxyl-containing polyurethane film substrate. A hydrophilic and hydrophobic copolymer containing a silane coupling unit (10 μL, 0.1 mol / L acetic acid was added to adjust the pH) was applied to the activated (hydroxyl-containing) polyurethane surface and cured in a 65°C oven for 24 hours. Subsequently, 10 wt% γ-PGA-NHS was dissolved in sodium bicarbonate, mixed with an equal volume of 5 wt% polyethyleneimine (PEI) aqueous solution, and applied to the upper surface of the coating to obtain a hydrogel coating with a double-layer network structure.

[0064] Figure 1 This is a schematic diagram of the construction of the wet-state responsive polyglutamic acid hydrogel coating of the present invention, indicating that the wet-state responsive polyglutamic acid hydrogel coating is composed of a bottom network structure and a top network structure that are interpenetratingly connected.

[0065] Comparative Example 1

[0066] The polyurethane film substrate was ultrasonically cleaned 3 times with anhydrous ethanol, then rinsed with deionized water 3 times, and completely dried for later use.

[0067] Comparative Example 2

[0068] To a mixed solution (2 mol / L) of hydroxyethyl acrylate (HEA) and 2-ethylhexyl acrylate (2-EHA), 3.7 μL of silane coupling agent TMSPMA, 10 μL of chain transfer agent CTA (1% V / V), and then 0.1 mol / L of photoinitiator L2959 were added, and a vortex mixer (2500 rpm) was used for 15 s to fully mix. The precursor was then sealed in a syringe and exposed to ultraviolet light (1200 mw / cm 2 ) was irradiated for 30 min to obtain a hydrophilic-hydrophobic copolymer p(HEA-co-EHA-co-TMSPMA) containing a silane coupling unit.

[0069] The polyurethane film substrate was ultrasonically cleaned 3 times with anhydrous ethanol, then rinsed with ionized water 3 times, and after complete drying, the surface of the material was activated for 3 minutes using a plasma processor to obtain a hydroxyl-containing polyurethane film substrate. A copolymer containing a silane coupling unit (10 μL was added, and 0.1 mol / L acetic acid was added to adjust the pH) was applied to the activated (hydroxyl-containing) polyurethane surface and cured in an oven at 65°C for 24 hours. A hydrogel coating containing only a bottom single network structure was obtained.

[0070] Comparative Example 3

[0071] To the hydroxyethyl acrylate (HEA) solution (2 mol / L), 3.7 μL of silane coupling agent TMSPMA, 10 μL of chain transfer agent CTA (1% V / V), and then 0.1 mol / L of photoinitiator L2959 were added, and a vortex mixer (2500 rpm) was used for 15 s to mix thoroughly. The precursor was then sealed in a syringe and exposed to ultraviolet light (1200 mw / cm 2 ) was irradiated for 30 min to obtain a hydrophilic-hydrophobic copolymer p(HEA-co-TMSPMA) containing silane coupling units.

[0072] After dissolving γ-polyglutamic acid (γ-PGA) with a molecular weight of 200w Da in anhydrous DMSO, 0.9g NHS and 1.48g EDC were added and stirred at room temperature for 12h under nitrogen atmosphere. Subsequently, the mixture was precipitated in ethanol / methanol (v / v=3 / 1), and the precipitate was washed three times with ethanol, acetone and n-hexane respectively. γ-PGA-NHS was obtained by vacuum drying.

[0073] The polyurethane film substrate was ultrasonically cleaned 3 times with anhydrous ethanol, then rinsed with ionized water 3 times, and after complete drying, the surface of the material was activated for 3 minutes using a plasma processor to obtain a hydroxyl-containing polyurethane film substrate. A hydrophilic and hydrophobic copolymer containing a silane coupling unit (10 μL was added, and 0.1 mol / L acetic acid was used to adjust the pH) was applied to the activated (hydroxyl-containing) polyurethane surface and cured in a 65°C oven for 24 hours. Subsequently, 10wt% γ-PGA-NHS was dissolved in sodium bicarbonate, mixed with an equal volume of 10wt% polylysine (PL) aqueous solution, and applied to the upper surface of the coating to obtain a hydrogel coating with a double-layer network structure.

[0074] Comparative Example 4

[0075] After dissolving γ-polyglutamic acid (γ-PGA) with a molecular weight of 200w Da in anhydrous DMSO, 0.9g NHS and 1.48g EDC were added and stirred at room temperature for 12h under nitrogen atmosphere. Subsequently, the mixture was precipitated in ethanol / methanol (v / v=3 / 1), and the precipitate was washed three times with ethanol, acetone and n-hexane respectively. γ-PGA-NHS was obtained by vacuum drying.

[0076] The polyurethane film substrate was ultrasonically cleaned 3 times with anhydrous ethanol, then rinsed with ionized water 3 times, and after being completely dried, the surface of the material was activated for 3 minutes using a plasma processor to obtain a hydroxyl-containing polyurethane film substrate. Subsequently, 10wt% γ-PGA-NHS was dissolved in sodium bicarbonate, mixed with an equal volume of 10wt% polylysine (PL) aqueous solution, and applied to the upper surface of the activated (hydroxyl-containing) polyurethane film substrate to obtain a hydrogel coating containing only a top network structure.

[0077] Performance tests of materials prepared in Examples 1-2 and Comparative Examples 1-4:

[0078] (1) Characterization of antibacterial properties

[0079] S. aureus and E. coli were selected as representative species of Gram-positive bacteria and Gram-negative bacteria, respectively, to test the antibacterial properties of the coating. Referring to JIS Z2801, the films of the examples and comparative examples were cut into 1.5 cm × 1.5 cm pieces, and 25 μL (10 6 CFU / mL) bacterial liquid, and covered with a 1cm×1cm polyethylene film, incubated at 37°C for 24h. Subsequently, the incubated sample was immersed in 2mL of PBS solution and ultrasonicated for 3min. Finally, the bacterial suspension was diluted and plated, and the plated solid culture plate was incubated at 37°C for 24h, and the colonies were counted and the number of colonies on each culture dish was calculated. Five measurements were performed for each sample to calculate the average value.

[0080] The antibacterial properties of the materials in Comparative Examples 1-4 and Examples 1-2 were tested as follows: Figure 2 shown.

[0081] like Figure 2 As shown, the surface of the uncoated comparative example 1 still has a large number of bacteria attached (wherein, S, aureus is a coccus, namely Staphylococcus aureus, scientific name Staphylococcus aureus, S. aureus; E. coli is a bacillus, namely Escherichia coli, scientific name Escherichia coli), and the number of bacteria in Examples 1-2 and Comparative Examples 3-4 is greatly reduced compared with Comparative Example 1, which may be related to the hydrophilicity and bactericidal properties of the coating. Comparative Example 2 without the upper (top) network still has a large number of bacteria, indicating that the upper hydrophilic antibacterial network plays an important role in anti-bacterial adhesion and bactericidal functions, so that the hydrogel coating with a double-layer network shows good antibacterial properties.

[0082] (2) Adhesion performance test

[0083] The adhesion energy between the hydrogel coating and the substrate material was determined by a 90 degree peel test. A hydrogel coating with a length of 60 mm, a width of 25 mm, and a thickness of 1 mm was formed on the substrate, and then tested on a universal testing machine (AGS-X, SHIMADZU, Kyoto, Japan) equipped with a 500N sensor at a constant peeling speed of 10 mm / min. The platform load (N) was divided by the width of the substrate and the width of the sample to obtain the peel strength. The adhesion performance between the materials and the substrate materials in Comparative Examples 2-4 and Example 1-2 is shown in FIG. Figure 3 .

[0084] like Figure 3As shown, the adhesion energy between Example 1, Example 2, and Comparative Example 2 and the substrate is higher than that of the hydrogel coating containing a fully hydrophilic underlying network (Comparative Example 3) and Comparative Example 4 without an underlying network. This indicates that the amphiphilic underlying network helps to increase the interaction between the hydrogel coating and the substrate in a wet environment, improves the mechanical properties of the hydrogel coating, and ultimately makes the hydrogel coating with a double-layer network show increased interfacial adhesion energy.

[0085] (3) Friction performance test

[0086] The lubricity of the coated catheter was tested using a fully automatic friction tester. The coated and unmodified catheters were fixed into the friction tester and immersed in an aqueous solution for 30 seconds. The friction test was then performed at a speed of 5 mm / s. The holding force was set to 3N, and the friction coefficient was recorded after 10 cycles.

[0087] The friction coefficients of the materials in Comparative Examples 1-4 and Examples 1-2 are as follows: Figure 4 shown.

[0088] like Figure 4 As shown, the hydrogel coatings in Examples 1-2 all exhibited the performance of reducing surface friction after 10 cycles in the aqueous solution medium, and the friction coefficients were all lower than that of Comparative Example 1 without a hydrogel coating. In addition, the friction coefficients of the materials in Examples 1-2 and Comparative Examples 3-4 were lower than that of Comparative Example 2 without a top layer network, which indicates that the strongly hydrophilic top layer network in the coating is the key to quickly forming an effective hydration layer in response to a wet environment, so that the hydrogel coating with a double-layer network has the best lubrication effect.

[0089] The above embodiments are only used to help understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A wet-responsive polyglutamic acid hydrogel coating, characterized in that: It is composed of the interpenetrating connection between the bottom network structure and the top network structure; The bottom layer network structure is obtained by coupling reaction between a hydroxyl-containing substrate and a hydrophilic-hydrophobic copolymer containing a silane coupling unit; The top layer network structure is obtained by amidation reaction of gamma-polyglutamic acid modified by N-hydroxysuccinimide and polyamino polymer.

2. The wet-state responsive polyglutamic acid hydrogel coating according to claim 1, characterized in that: The hydrophilic-hydrophobic copolymer containing silane coupling units is prepared by free radical polymerization of a silane coupling agent, acetic acid, a chain transfer agent, a vinyl monomer and a photoinitiator; The silane coupling agent contains vinyl; The vinyl monomer is selected from a mixture of a hydrophilic vinyl monomer and a hydrophobic vinyl monomer; The photoinitiator is selected from cleavage-type photoinitiators.

3. The wet-state responsive polyglutamic acid hydrogel coating according to claim 2, characterized in that: The molar ratio of the silane coupling agent to the vinyl monomer is (0.00001-1):1; The molar ratio of the hydrophilic vinyl monomer to the hydrophobic vinyl monomer in the vinyl monomer is (0.1-10):

1.

4. The wet-state responsive polyglutamic acid hydrogel coating according to claim 2 or 3, characterized in that: The silane coupling agent is selected from vinyl trimethoxy silane, vinyl triethoxy silane or 3-(trimethoxysilyl) propyl methacrylate; The hydrophilic vinyl monomer is selected from one or more of acrylic acid, hydroxyethyl acrylate, dimethylaminoethyl acrylate, methacrylic acid, hydroxyethyl methacrylate, dimethylaminoethyl methacrylate, and poly(ethylene glycol) methacrylate; The hydrophobic vinyl monomer is selected from one or more of butyl acrylate, 2-ethylhexyl acrylate, benzyl acrylate, butyl methacrylate, 2-ethylhexyl methacrylate, and benzyl methacrylate; The cleavage-type photoinitiator is selected from α-hydroxyketone derivative photoinitiator Irgacure 2959, photoinitiator 1173 or phosphonyl initiator LAP.

5. The wet-state responsive polyglutamic acid hydrogel coating according to claim 1, characterized in that: The hydroxyl-containing substrate is obtained by surface hydroxylation treatment of elastomer, plastic, glass, ceramic or metal.

6. The moisture-responsive polyglutamic acid hydrogel coating according to claim 1, characterized in that: The polyamino polymer is selected from one or more of polylysine, polyethyleneimine, polyhexamethyleneguanidine hydrochloride, and polyhexamethylenemonoguanidine hydrochloride.

7. The method for preparing the wet-state responsive polyglutamic acid hydrogel coating according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) coating a hydrophilic-hydrophobic copolymer containing a silane coupling unit on the surface of a hydroxyl-containing substrate and curing the coating to obtain the underlying network structure; (2) Mixing and reacting N-hydroxysuccinimide-modified γ-polyglutamic acid and a polyamino polymer in an alkaline environment and coating the mixture on the surface of the underlying network structure to obtain the wet-state responsive polyglutamic acid hydrogel coating.

8. The preparation method according to claim 7, characterized in that: The curing method in step (1) is ultraviolet light curing; The temperature of the UV curing is 25°C-100°C; The UV curing UV light intensity is 10-2000mw / cm 2 ; The ultraviolet light irradiation time of the ultraviolet light curing is 5-60 minutes.

9. The preparation method according to claim 7, characterized in that: The molar ratio of the N-hydroxysuccinimide-modified γ-polyglutamic acid to the polyamino polymer is 1:(0.01-1).

10. Use of the moisture-responsive polyglutamate hydrogel coating according to any one of claims 1 to 6 or the moisture-responsive polyglutamate hydrogel coating prepared by the preparation method according to any one of claims 7 to 9 in implantable medical devices, wound care or tissue engineering.

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