Preparation method of medical catheter with hydrogel coating with effective lubrication, long-term antibiosis and antithrombosis functions

Abstract

The invention discloses a method for preparing a medical catheter by using a hydrogel coating with effective lubrication, long-term antibiosis and antithrombosis. The method comprises the following steps: mixing a vinyl monomer, a vinyl modified monomer, a cross-linking agent and a photoinitiator to form a hydrogel pre-polymerized solution; the preparation method comprises the following steps: carrying out base catalysis balance, grafting a silane coupling agent with double bonds on the surface of a conduit, and immersing the conduit into an ethanol solution containing a hydrophobic initiator, so that the hydrophobic initiator permeates into a substrate for carrying out a subsequent photocuring reaction. The prepared hydrogel pre-polymerized solution covers the surface of a base material with double bonds on the surface, and the medical catheter material with a hydrogel coating which is effective in lubrication, antibacterial for a long time and resistant to thrombosis is obtained through ultraviolet cross-linking curing. A double-bond reactive group is bridged on the surface of a base material through a base catalysis equilibrium method, a bonding layer is formed on the surface, and the double-bond group contained in the bonding layer is covalently connected with a hydrogel coating, so that tight combination between a polymer network and a solid surface is realized.

Description

Technical Field

[0001] The invention relates to the field of medical catheters, and in particular to a method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties. Background Art

[0002] Medical catheters are an integral part of modern medicine, greatly improving the quality of treatment and relief of diseases. However, most catheters (such as polyvinyl chloride, polyurethane, and rubber) are made of hydrophobic polymer materials, which may cause undue friction with human tissue. Therefore, the outer surface of the catheter must be fully lubricated to avoid tissue friction. In addition, catheters inserted into the body can adsorb plasma and proteins, further promoting the adsorption of platelets, leukocytes, and erythrocytes, inevitably leading to inflammation. Therefore, there is an urgent need for catheters to have excellent antibacterial and antifouling properties.

[0003] Hydrogels are highly hydrophilic and soft (Young's modulus ≈ 30 kPa) and are widely used in medical catheter coatings. Due to their good water retention and wettability, they are endowed with a certain hydration lubrication effect, and the addition of lubricating polymers can also improve their lubrication properties. Studies have shown that xylitol, a natural product, can inhibit the growth of various bacteria and prevent biofilm formation, and has been proven to be an effective component for designing multifunctional wound dressing hydrogels.

[0004] However, extremely low friction usually requires the hydrogel to have a high degree of hydration, which in turn has a negative impact on the mechanical properties (such as toughness and strength), thereby weakening the wear resistance. Zwitterionic sulfobetaine was selected to regulate the swelling properties of the gel. The formed 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1-sulfonic acid salt (pSB) network "locks" the entire hydrogel through strong intermolecular and intramolecular electrostatic interactions, thereby limiting the swelling of the gel.

[0005] At the same time, hydrogels have a three-dimensional network structure and can provide sufficient capacity to accommodate various antibacterial molecules, including antibiotics, antibacterial compounds, inorganic antibacterial agents, etc. Therefore, hydrogel coatings have become potential effective antibacterial coatings. Cefuroxime sodium, a β-lactam antibiotic, can bind to penicillin binding protein (PBP) required for bacterial cell wall synthesis. When the drug binds to the enzyme, the PBP enzyme loses its activity, thereby hindering the synthesis of bacterial cell walls, resulting in bacterial cell wall defects, water infiltration, cell swelling, etc., thereby achieving the effect of sterilization. Since human eukaryotic cells do not have cell walls, they are not affected by drugs. This type of antibiotic has the advantages of strong bactericidal activity, low toxicity, wide indications and good clinical efficacy.

[0006] Since medical catheters are widely in demand, people need to explore simpler production procedures to reduce costs. In addition, the in vivo biocompatibility and actual clinical effects of hydrogel coatings always need to be strictly verified. Clinical research on medical catheter-related infections requires a lot of data support and a long experimental cycle, so it is relatively difficult to conduct clinical research. Even so, hydrogel coatings are still considered to be one of the candidates for reducing medical catheter-related infections. Summary of the invention

[0007] In view of the problems of related infection and thrombosis in the use of the above-mentioned medical catheters, the purpose of the present invention is to provide a method for preparing a medical catheter with a hydrogel coating having effective lubrication, long-term antibacterial and anti-thrombotic properties. By constructing a functional hydrogel coating on the surface of the medical catheter and giving the catheter lubrication, long-term antibacterial and anti-thrombotic properties, the catheter can be used in medical mechanical equipment.

[0008] The first aspect of the present invention relates to a xylitol hydrogel coating loaded with an antimicrobial agent, which is bridged onto a medical catheter by a photocuring method to impart effective antimicrobial and antifouling properties to the catheter.

[0009] The scope of the present invention relates to a hydrogel prepolymer solution loaded with antibacterial monomers, which takes a medical catheter as a substrate and solidifies the hydrogel on its surface by photocuring to form a stable hydrogel coating.

[0010] According to an embodiment of the present invention, the selected vinyl monomer content accounts for 1-40% of the solution mass ratio, the alcohol-modified hexyl monomer in the modified vinyl monomer accounts for 1-50% of the solution mass ratio, the antibacterial agent modified vinyl monomer accounts for 0-5% of the solution mass ratio, the cross-linking agent accounts for less than 1 mol% of the monomer ratio, preferably 0.5 mol%, and the photoinitiator accounts for less than 0.1 mol% of the monomer ratio, preferably 0.05 mol%.

[0011] In order to achieve the above-mentioned invention object, the technical solution adopted by the present invention is:

[0012] The present invention provides a method for preparing a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties for use in medical catheters. The preparation method comprises:

[0013] (1) Preparing a hydrogel prepolymer solution: mixing a general vinyl monomer, a vinyl modified monomer, a crosslinking agent, and a photoinitiator to form a hydrogel prepolymer solution.

[0014] The vinyl monomer is selected from at least one of the following: acrylate, methacrylate, acrylic acid, acrylamide, acrylonitrile, [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, 2-carboxyl-N,N-dimethyl-N-(3'-acrylamidopropyl)ethylamine inner salt, preferably acrylic acid and acrylamide.

[0015] The modified vinyl monomer is obtained by esterification reaction, and the two different modified vinyl monomer mixtures include the following two schemes:

[0016] Scheme 1: Hexene-modified alcohol monomers include: polyols, vinyl monomers, coupling agents, and catalysts.

[0017] The polyol is at least one selected from the following: sorbitol, xylitol, mannitol, glucose, lactose, preferably xylitol.

[0018] The vinyl monomer is at least one selected from the following: acrylate, methacrylate, acrylic acid, acrylamide, acrylonitrile, [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, 2-carboxyl-N,N-dimethyl-N-(3'-acrylamidopropyl)ethylamine inner salt. Acrylic acid is preferred.

[0019] The coupling reagent is at least one selected from the following: DCC (dicyclohexylcarbodiimide), EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride), DIC (1,3-diisopropylcarbodiimide), preferably EDC.

[0020] The pyridine catalyst is selected from one or more of the following:

[0021]

[0022] Option 2: The vinyl-modified antibacterial agent monomer includes: β-lactam antibacterial agent, polyol, vinyl monomer, coupling reagent, and catalyst.

[0023] The β-lactam antibiotic is selected from one or more cephalosporin antibiotics: cephalexin, cephradine, cefazolin, cefuroxime, cefmandole, cefaclor, cefotaxime, ceftazidime, ceftriaxone, cefoperazone, ceftizoxime, cefepime, and cefpirome. Cefuroxime is preferred.

[0024] The polyol is at least one selected from the following: sorbitol, xylitol, mannitol, glucose, and lactose.

[0025] The vinyl monomer is at least one selected from the following: acrylate, methacrylate, acrylic acid, acrylamide, acrylonitrile, [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, 2-carboxy-N,N-dimethyl-N-(3′-acrylamidopropyl)ethylamine inner salt.

[0026] The coupling reagent is at least one selected from the following: DCC (dicyclohexylcarbodiimide), EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride), DIC (1,3-diisopropylcarbodiimide).

[0027] The pyridine catalyst is selected from one or more of the above scheme one.

[0028] The crosslinking agent is selected from one or more of the following: divinylbenzene, diisocyanate, N,N-methylenebisacrylamide (MBA), ethylene glycol dimethacrylate and its derivatives.

[0029] The photoinitiator is selected from one or more of the following: diphenylacetophenone, α, α-dimethoxy-α-phenylacetophenone, α, α-diethoxyacetophenone, α-hydroxyalkyl phenone, α-aminoalkyl phenone, aromatic acylphosphine oxide, bisbenzoylphenylphosphine oxide, benzophenone, 2,4-dihydroxybenzophenone, Michler's ketone, thiopropoxythioxanthone, 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, and isopropylthioxanthone.

[0030] (2) pre-treating the surface of the medical catheter, grafting a silane coupling agent with a double bond on the surface through base catalytic equilibrium, and then immersing the surface in an ethanol solution containing a hydrophobic initiator, so that the hydrophobic initiator penetrates into the substrate for subsequent photocuring reaction;

[0031] The medical catheter is selected from one or more of the following: polyvinyl chloride (PVC), silicone rubber (PDMS elastomer), and polyurethane (PU).

[0032] The base catalytic equilibrium mixed solution comprises: a basic compound accounting for 1-10% of the solution, a silane coupling agent accounting for 1-50% of the solution, and a solvent.

[0033] The alkaline compound is at least one or more of the following: sodium hydroxide, barium hydroxide, calcium hydroxide, potassium hydroxide, copper hydroxide, iron hydroxide, magnesium hydroxide, and sodium carbonate.

[0034] The silane coupling agent is at least one or more of the following: vinyl triethoxysilane, vinyl trimethoxysilane, butadienyl triethoxysilane, and 3-(methacryloyloxy)propyl trimethoxysilane.

[0035] At least one or more of the following are selected as the solvent: water, methanol, ethanol, isopropanol, acetone, glycerol, acetonitrile, and ethylene glycol.

[0036] The hydrophobic initiator is benzophenone, and the mass concentration of the hydrophobic initiator in the ethanol solution containing the hydrophobic initiator is in the range of 1-30%.

[0037] (3) The hydrogel prepolymer solution obtained in step (1) is covered on the surface of the pretreated substrate obtained in step (2), and cross-linked and cured under ultraviolet light to obtain a medical catheter material having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties.

[0038] The power of the ultraviolet curing lamp is 10-100W, and the curing time is 0.5-6h.

[0039] Compared with the prior art, the beneficial effects of the present invention are mainly reflected in:

[0040] Through the method of base catalytic equilibrium, the double bond reactive groups in the silane coupling agent are bridged on the surface of the substrate to form a bonding layer on the surface. The double bond groups contained in the bonding layer are covalently linked to the hydrogel coating, realizing a close bond between the polymer network and the solid surface; monomers prepared from polyols are selected to participate in the preparation of the hydrogel coating, the hydrophilic lubrication properties of the hydrogel are regulated, and the strong hydration of the hydrogel coating is used to give the gel coating good lubrication and antifouling effects; β-lactam antibiotic modified monomers are introduced into the formula to give the gel coating good antibacterial properties. This method is simple and easy to operate, low cost, and enables the catheter to have antibacterial, antithrombotic, and antifouling properties at the same time, providing broad value for biomedical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 It is the H NMR spectrum of hexenyl-modified alcohol monomer;

[0042] Figure 2 It is the H NMR spectrum of vinyl modified antibacterial agent monomer;

[0043] Figure 3 The colony photos of the blank group and sample 3 cultured for 21 days;

[0044] Figure 4 Laser confocal images of the blank group and sample 3 cultured for 21 days;

[0045] Figure 5 This is a comparison chart of the in vitro anti-thrombotic effects of the blank group and the catheter containing coating C. DETAILED DESCRIPTION

[0046] The present invention is further described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto:

[0047] Example 1

[0048] Preparation of xylitol-acrylate (XA) stock solution A (20 wt%):

[0049] Add 16.1g of deionized water to a 100mL dry round-bottom flask, weigh 5g of xylitol crystals, 4.52g of 4-dimethylaminopyridine, 6.31g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and 2.37g of acrylic acid in the flask, stir until completely dissolved, and stir the reaction mixture at room temperature for 24h. The prepared stock solution is a light yellow transparent liquid. The concentration of the xylitol-acrylate stock solution is 20wt%. The degree of acrylate of xylitol is 83%. The H NMR spectrum is shown in the attached Figure 1 .

[0050] Preparation of Cefuroxime Axetil (CS) Stock Solution B:

[0051] Add 2g of deionized water to a 100mL dry round-bottom flask, weigh 0.3g of xylitol crystals, 0.5418g of tetramethylaminopyridine, 0.7568g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 0.1421g of acrylic acid, and 0.8810g of cefuroxime in the flask, stir until completely dissolved, and stir the reaction mixture at room temperature 25°C for 24h. The prepared stock solution is a reddish brown clear liquid. The concentration of the cefuroxime axetil (CS) stock solution is 25wt%. The degree of esterification of cefuroxime is 96%. The H NMR spectrum is shown in the attached Figure 2 .

[0052] Preparation of hydrogel prepolymerization solution C:

[0053] Add 0.1 g acrylic acid, 0.1 g acrylamide, 0.25 g stock solution A, 4.6 g 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1-sulfonic acid inner salt, 0.6 g stock solution B, 0.015 g N,N'-methylenebisacrylamide, 0.0022 g I2959 photoinitiator, and 1.335 g deionized water into a glass bottle and stir until a uniform solution is obtained to obtain a hydrogel prepolymer solution C.

[0054] Substrate selection and preparation (taking PDMS elastomer as an example):

[0055] According to the literature [Langmuir 2013, 29, 12432-12442], the PDMS substrate was prepared using two parts of the Dow Corning Sylgard 184 elastomer kit. The liquid precursors in the kit were mixed at a ratio of 10:1 and cured in an oven at 80°C for 5 hours to obtain a PDMS substrate.

[0056] Preparation of hydrogel coating on PDMS substrate:

[0057] The prepared PDMS elastomer film was ultrasonically treated in a methanol solution containing 1wt% potassium hydroxide and 10wt% 3-methacryloxypropyltrimethoxysilane for 1 hour. The treated substrate was ultrasonically washed with methanol for 5 minutes and then immersed in 50mL DCM for 30 minutes to remove excess impurities. Subsequently, the treated substrate was dried under a nitrogen stream. The substrate was then immersed in an ethanol solution containing 10wt% benzophenone for 10 minutes to diffuse BP into the substrate. 4 microliters of hydrogel prepolymer solution C were transferred using a pipette and covered on a PDMS substrate with a diameter of 1 cm. The substrate was covered with a transparent release film (polyethylene terephthalate) and irradiated under an ultraviolet lamp with a wavelength of 365nm and a power of 50W for 3 hours, the release film was removed, and the sample was immersed in deionized water for 12h to remove unreacted monomers and impurities. A hydrogel coating sample 1 was obtained.

[0058] Escherichia coli (ATCC 225922, E. coli) and Staphylococcus aureus (CMCC 26003, S. aureus) were selected and cultured in liquid LB medium at 37°C in a constant temperature shaker at 150 rpm for 24 h. The bacterial solution was finally diluted to a concentration of 1×10 6 CFU mL -1 , the prepared sample 1 with a diameter of 1 cm was immersed in 3 mL of diluted bacterial solution of Escherichia coli and Staphylococcus aureus, respectively, and cultured at a constant temperature shaker at 37°C at a speed of 150 rpm for 21 days to allow bacteria to adhere. Subsequently, the sample was removed from the culture medium and rinsed 3 times with 10 mL of deionized water to remove non-adherent bacteria. The bacteria adhering to the sample were collected by ultrasonically treating the sample in a centrifuge tube containing 2 mL of deionized water for 2 minutes. The mixed solution in the centrifuge tube was diluted 100 times, and 50 μL of the diluted mixed solution was taken on solid LB medium. After incubation at 37°C for 24 hours, the number of bacterial colonies on the LB agar plate was calculated by multiplying the number of bacterial colonies on the LB agar plate by the dilution factor.

[0059] The inhibition rate was calculated by the following formula:

[0060]

[0061] The anti-thrombotic effect of the gel coating was detected by an in vitro anti-thrombotic dynamic circulation experiment using a peristaltic pump. The medical catheter with the inner wall containing the polymer C hydrogel coating was rinsed three times with 75% ethanol, sterile saline, sodium citrate and sterile saline. 20mL of fresh rabbit blood containing an anticoagulant was injected into the inside of the pipe and then connected to the end to close into a loop. 0.2MCaCl2 physiological saline solution was injected into the anticoagulated rabbit blood to eliminate the interference of the anticoagulant, thereby accelerating thrombosis. The blood flow rate of the peristaltic pump was set to 0.2L / min. The circuit was stopped after the rabbit blood circulated for 1h. The sample was washed with PBS, then photographed and weighed. The weight of the thrombus formed in the passage of the polymer C hydrogel-coated medical catheter was 114.4mg.

[0062] Comparative Example 1

[0063] Preparation of hydrogel coating on PDMS substrate is the same as in Example 1

[0064] Escherichia coli (ATCC 225922, E. coli) and Staphylococcus aureus (CMCC 26003, S. aureus) were selected and cultured in liquid LB medium at 37°C in a constant temperature shaker at 150 rpm for 24 h. The bacterial solution was finally diluted to a concentration of 1×10 6 CFU mL-1, the prepared PDMS substrate with a diameter of 1 cm was used as a blank control group and immersed in 3 mL of diluted bacterial solution of Escherichia coli and Staphylococcus aureus, respectively, and cultured at 150 rpm in a constant temperature shaker at 37 ° C for 21 days to allow bacteria to adhere. Subsequently, the sample was removed from the culture medium and rinsed 3 times with 10 mL of deionized water to remove non-adherent bacteria. The bacteria adhering to the sample were collected by ultrasonically treating the sample in a centrifuge tube containing 2 mL of deionized water for 2 minutes. The mixed solution in the centrifuge tube was diluted 100 times, and 50 μL of the diluted mixed solution was taken on solid LB medium. After incubation at 37 ° C for 24 hours, the number of bacterial colonies on the LB agar plate was calculated by multiplying the number of bacterial colonies on the LB agar plate by the dilution factor.

[0065] The calculation formula is the same as that in Example 1.

[0066] By comparing with the blank control group, the antibacterial rates of sample 1 against Escherichia coli and Staphylococcus aureus were 57.7% and 96.3% respectively. See attached for comparison pictures of the coated plates Figure 3 .

[0067] After culturing the samples of bacteria cultured in the same manner as above for 21 days, the samples were removed from the culture medium, rinsed three times with 10 mL of deionized water to remove non-adherent bacteria, and treated with a mixture of green SYTO9 and red propidium iodide at room temperature in the dark for 15 minutes. The adhered bacterial cells and their viability were observed using a laser confocal scanning microscope. See Appendix Figure 4 .

[0068] The sample preparation steps for the in vitro anti-thrombotic experiment were the same as those in Example 1. The test sample was a medical catheter without a coating as the control group. The weight of the thrombus formed in the passage of the medical catheter without a coating was measured to be 442.4 mg. The anti-thrombotic rate of the medical catheter coated with polymer C hydrogel was increased by 286.7% compared with the control group. See attached Figure 5 .

[0069] By comparing Example 1 with Comparative Example 1, it can be seen that the addition of polyol monomers and the introduction of β-lactam antibiotic modified monomers improve the hydrophilic lubrication properties of the hydrogel, and utilize strong hydration to give the gel coating good anti-fouling and anti-thrombotic effects, while giving the gel coating good antibacterial properties, significantly improving the antibacterial effect of the hydrogel coating on Gram-negative and Gram-positive bacteria.

[0070] Example 2

[0071] The preparation methods of stock solution A and stock solution B are the same as in Example 1.

[0072] Preparation of functional hydrogel prepolymerization solution D:

[0073] Add 0.8 g acrylic acid, 0.8 g acrylamide, 2 g stock solution A, 0.015 g N,N'-methylenebisacrylamide, 0.05 g I2959 photoinitiator, and 1.335 deionized water into a glass bottle and stir until a uniform solution is obtained to obtain a hydrogel prepolymer solution D.

[0074] The preparation method of the PDMS substrate is the same as that in Example 1.

[0075] Preparation of hydrogel coating on PDMS substrate:

[0076] The pretreatment process of the PDMS substrate is the same as that of Example 1. Then, 4 μl of the hydrogel prepolymer solution D is transferred using a pipette and covered on a 1 cm diameter PDMS substrate that has been pretreated. The substrate is covered with a transparent release film (polyethylene terephthalate) and irradiated under a UV lamp with a wavelength of 365 nm and a power of 50 W for 60 minutes. The release film is removed and the sample is immersed in deionized water for 12 hours to remove unreacted monomers and impurities. A hydrogel coating sample 2 is obtained.

[0077] Using the same testing method as in Example 1, the antibacterial rates of sample 2 against Escherichia coli and Staphylococcus aureus were 35.2% and 93.7%.

[0078] Example 3

[0079] The preparation methods of stock solution A and stock solution B are the same as in Example 1.

[0080] Preparation of functional hydrogel prepolymer solution E:

[0081] Add 0.1 g acrylic acid, 0.1 g acrylamide, 0.25 g stock solution A, 4.75 g 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1-sulfonic acid inner salt, 0.015 g N,N'-methylenebisacrylamide, 0.0022 g I2959 photoinitiator, and 7.3 g deionized water into a glass bottle, stir until a uniform solution is obtained to obtain a hydrogel prepolymer solution E.

[0082] The preparation method of the PDMS substrate is the same as that in Example 1.

[0083] Preparation of hydrogel coating on PDMS substrate:

[0084] The pretreatment process of the PDMS substrate is the same as that of Example 1. Then, 4 μl of the hydrogel prepolymer solution E is transferred using a pipette and covered on a 1 cm diameter PDMS substrate that has been pretreated. The substrate is covered with a transparent release film (polyethylene terephthalate) and irradiated under a UV lamp with a wavelength of 365 nm and a power of 50 W for 60 minutes. The release film is removed and the sample is immersed in deionized water for 12 hours to remove unreacted monomers and impurities. A hydrogel coating sample 3 is obtained.

[0085] Using the same testing method as in Example 1, the antibacterial rates of sample 3 against Escherichia coli and Staphylococcus aureus were 45.7% and 93.9% respectively.

[0086] Example 4

[0087] The preparation methods of stock solution A and stock solution B are the same as in Example 1.

[0088] Preparation of functional hydrogel prepolymer solution F:

[0089] Add 0.1 g acrylic acid, 0.1 g acrylamide, 0.25 g stock solution A, 4.7 g 3-[N,N-dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]ammonium]propane-1-sulfonic acid inner salt, 0.2 g stock solution B, 0.015 g N,N'-methylenebisacrylamide, 0.0022 g I2959 photoinitiator, and 7.15 g deionized water into a glass bottle and stir until a uniform solution is obtained to obtain a hydrogel prepolymer solution F.

[0090] The preparation method of the PDMS substrate is the same as that in Example 1.

[0091] Preparation of hydrogel coating on PDMS substrate:

[0092] The pretreatment process of the PDMS substrate is the same as that of Example 1. Then, 4 μl of the hydrogel prepolymer solution F is transferred using a pipette and covered on a 1 cm diameter PDMS substrate that has been pretreated. The substrate is covered with a transparent release film (polyethylene terephthalate) and irradiated under a UV lamp with a wavelength of 365 nm and a power of 50 W for 60 minutes. The release film is removed and the sample is immersed in deionized water for 12 hours to remove unreacted monomers and impurities. A hydrogel coating sample 4 is obtained.

[0093] Using the same testing method as in Example 1, the antibacterial rates of sample 4 against Escherichia coli and Staphylococcus aureus were 51.8% and 95.5%.

[0094] The above embodiments of the present invention are intended to illustrate the present invention rather than to limit the present invention. Any changes within the equivalent meaning and scope of the claims of the present invention should be considered to be included in the scope of the claims.

Claims

1. A method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties, characterized in that: The following steps are involved: (1) mixing a vinyl monomer, a vinyl modified monomer, a crosslinking agent, and a photoinitiator to form a hydrogel prepolymer solution; (2) pre-treating the surface of the medical catheter, grafting a silane coupling agent with double bonds on the surface of the medical catheter through base catalytic equilibrium, and then immersing the medical catheter in an ethanol solution containing a hydrophobic initiator to allow the hydrophobic initiator to penetrate the surface of the medical catheter to obtain a substrate surface containing double bonds; (3) The hydrogel prepolymer solution obtained in step (1) is coated on the surface of the substrate having double bonds obtained in step (2), and cross-linked and cured under ultraviolet light to obtain a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties.

2. The method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties according to claim 1, characterized in that: In step (1), the vinyl monomer is selected from at least one of the following: acrylate, methacrylate, acrylic acid, acrylamide, acrylonitrile, [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, 2-carboxy-N,N-dimethyl-N-(3′-acrylamidopropyl)ethylamine inner salt.

3. The method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties according to claim 1, characterized in that: In step (1), the vinyl-modified monomer is a hexenyl-modified alcohol monomer prepared by a first esterification reaction or a vinyl-modified antibacterial agent monomer prepared by a second esterification reaction.

4. The method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties according to claim 3, characterized in that: In step (1), the hexenyl-modified alcohol monomer prepared by the first esterification reaction specifically comprises: It is prepared by esterification reaction using polyol, vinyl monomer, coupling reagent and pyridine catalyst; The polyol is at least one selected from the following: sorbitol, xylitol, mannitol, glucose, lactose; The vinyl monomer is at least one selected from the following: acrylate, methacrylate, acrylic acid, acrylamide, acrylonitrile, [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, 2-carboxyl-N,N-dimethyl-N-(3'-acrylamidopropyl)ethylamine inner salt; The coupling reagent is at least one selected from the following: dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 1,3-diisopropylcarbodiimide; The pyridine catalyst is selected from one or more of the following:

5. The method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties according to claim 3, characterized in that: In step (1), the vinyl-modified antibacterial agent monomer prepared by the second esterification reaction specifically comprises: It is prepared by esterification reaction using β-lactam antimicrobial agent, polyol, vinyl monomer, coupling reagent and pyridine catalyst; The β-lactam antibiotic is selected from one or more cephalosporin antibiotics: cephalexin, cephradine, cefazolin, cefuroxime, cefmandole, cefaclor, cefotaxime, ceftazidime, ceftriaxone, cefoperazone, ceftizoxime, cefepime, and cefpirome; The polyol is at least one selected from the following: sorbitol, xylitol, mannitol, glucose, lactose; The vinyl monomer is at least one selected from the following: acrylate, methacrylate, acrylic acid, acrylamide, acrylonitrile, [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide, 2-carboxyl-N,N-dimethyl-N-(3′-acrylamidopropyl)ethylamine inner salt; The coupling reagent is at least one selected from the following: dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 1,3-diisopropylcarbodiimide; The pyridine catalyst is selected from one or more of the following:

6. The method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties according to claim 1, characterized in that: In step (1), the cross-linking agent is selected from one or more of the following: divinylbenzene, diisocyanate, N,N-methylenebisacrylamide, ethylene glycol dimethacrylate and its derivatives; The photoinitiator is selected from one or more of the following: diphenylacetophenone, α, α-dimethoxy-α-phenylacetophenone, α, α-diethoxyacetophenone, α-hydroxyalkyl phenone, α-aminoalkyl phenone, aromatic acylphosphine oxide, bisbenzoylphenylphosphine oxide, benzophenone, 2,4-dihydroxybenzophenone, Michler's ketone, thiopropoxythioxanthone, 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, and isopropylthioxanthone.

7. The method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties according to claim 1, characterized in that: In step (2), the base-catalyzed equilibrium adopts a base-catalyzed equilibrium mixed solution, and the base-catalyzed equilibrium mixed solution comprises: an alkaline compound, a silane coupling agent and a solvent, the mass fraction of the alkaline compound in the base-catalyzed equilibrium mixed solution is 1-10%, and the mass fraction of the silane coupling agent in the base-catalyzed equilibrium mixed solution is 1-50%; The alkaline compound is at least one or more of the following: sodium hydroxide, barium hydroxide, calcium hydroxide, potassium hydroxide, copper hydroxide, iron hydroxide, magnesium hydroxide, sodium carbonate; The silane coupling agent is selected from at least one or more of the following: vinyl triethoxysilane, vinyl trimethoxysilane, butadienyl triethoxysilane, 3-(methacryloyloxy)propyl trimethoxysilane; The solvent is at least one or more of the following: water, methanol, ethanol, isopropanol, acetone, glycerol, acetonitrile, and ethylene glycol.

8. The method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties according to claim 1, characterized in that: In step (2), the hydrophobic initiator is benzophenone.

9. The method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties according to claim 1, characterized in that: In step (3), the ultraviolet light irradiation uses an ultraviolet curing lamp with a power of 10-100W.

10. The method for preparing a medical catheter having a hydrogel coating with effective lubrication, long-term antibacterial and anti-thrombotic properties according to claim 1, characterized in that: In step (3), the cross-linking curing time under ultraviolet light is 0.5-6h.

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