Method for firmly modifying surface of medical catheter with hydrophilic lubricating antibacterial hydrogel coating

Abstract

The invention provides a method for firmly modifying the surface of a medical catheter with a hydrophilic lubricating antibacterial hydrogel coating, which comprises the following steps: immersing the cleaned medical catheter in a waterborne polyurethane solution, taking out the medical catheter, and drying the medical catheter in a drying oven to obtain the medical catheter with the surface coated with a waterborne polyurethane layer; the medical catheter with the surface coated with the waterborne polyurethane layer is soaked in the pre-gel solution, the base material is taken out of the solution, and the hydrophilic lubricating antibacterial hydrogel coating is formed on the surface of the medical catheter through ultraviolet-initiated polymerization. The hydrogel coating prepared by the invention shows strong interface bonding force with the surface of the medical catheter due to the existence of the waterborne polyurethane layer, and has good hydrophilicity (WCA = 24.6 degrees) and lower surface friction coefficient (COF = 0.05) at the same time. In addition, the hydrogel coating has excellent antibacterial performance on escherichia coli (gram-negative bacteria) and bacillus subtilis (gram-positive bacteria) under the synergistic effect of zinc sulfate heptahydrate and quaternary ammonium salt chitosan. The problems of firm modification, hydrophilic lubrication and antibiosis of the hydrogel coating in surface functionalization of the medical catheter are solved.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a method for firmly modifying a hydrophilic, lubricating, and antibacterial hydrogel coating on the surface of a medical catheter. Background Art

[0002] Medical catheters are mostly made of hydrophobic materials. When inserted into the human body, they often cause tissue friction and bacterial infection due to the hydrophobic surface. Modifying the surface of medical catheters with hydrophilic lubricating antibacterial coatings can help reduce friction with human tissues, reduce the risk of bacterial infection, and reduce the pain of patients.

[0003] As a soft and wet material, hydrogel has excellent biocompatibility, hydrophilicity, and mechanical properties similar to human soft tissue. It is an ideal material for medical catheter coating. Existing hydrogel coating preparation methods successfully modify hydrogel coatings on the surface of medical catheters, but there are generally defects to varying degrees. For example, surface initiation and surface bridging strategies usually require specific functional groups to combine with pretreated substrates, and there are common difficulties such as poor substrate versatility and the need for specific reaction systems. Therefore, how to firmly modify hydrophilic, lubricating, and antibacterial hydrogel coatings on the surface of medical catheters remains a scientific difficulty in this field. Summary of the invention

[0004] The object of the present invention is to provide a method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating, so as to solve the problems raised in the above-mentioned background technology.

[0005] To achieve the above object, the present invention discloses a method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, and antibacterial hydrogel coating, comprising the following steps: (1) The medical catheter substrate is washed three times with deionized water and ethanol alternately to remove surface impurities, and then placed in an oven at a temperature of 40-60° C. to dry; (2) immersing the medical catheter cleaned in step (1) into an aqueous polyurethane solution, taking it out, and drying it in an oven at a temperature of 40-60° C. to obtain a medical catheter with a surface coated with an aqueous polyurethane layer; (3) dissolving the zwitterionic monomer, nonionic compound, zinc sulfate heptahydrate, and quaternary ammonium salt chitosan uniformly in deionized water, then adding a crosslinking agent and a photoinitiator, stirring uniformly, and then performing ultrasonic treatment to remove bubbles to obtain a pre-gel solution; (4) Immersing the medical catheter obtained in step (2) into the pregel solution obtained in step (3), taking the medical catheter out of the pregel solution, and irradiating it under ultraviolet light, thereby forming a hydrophilic, lubricating, and antibacterial hydrogel coating on the surface of the medical catheter.

[0006] Preferably, the aqueous polyurethane solution in step (2) is RM-2020PN aqueous polyurethane.

[0007] Preferably, the amount of the zwitterionic monomer in step (3) is 1-3 parts by mass, the amount of the nonionic compound is 1-3 parts by mass, the amount of zinc sulfate heptahydrate is 0.05-0.2 parts by mass, the amount of quaternary ammonium salt chitosan is 0.4-0.5 parts by mass, the amount of deionized water is 8-12 parts by mass, the amount of the crosslinking agent is 0.005-0.01 parts by mass, and the amount of the photoinitiator is 0.01-0.02 parts by mass.

[0008] Preferably, the zwitterionic monomer in step (3) is any one or more of methacrylate sulfobetaine, methacrylate carboxybetaine, and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonatepropyl)ammonium hydroxide.

[0009] Preferably, the non-ionic compound in step (3) is any one or more of N-vinyl pyrrolidone and polyvinyl pyrrolidone.

[0010] Preferably, the cross-linking agent in step (3) is any one or more of polyethylene glycol dimethacrylate and N, N-methylenebisacrylamide.

[0011] Preferably, the photoinitiator in step (3) is I2959.

[0012] Preferably, the intensity of the ultraviolet light in step (4) is 500-800 Mw / cm 2 , the illumination time is 20-40min.

[0013] Preferably, the medical catheter is made of any one of polyvinyl chloride, polyethylene, polyurethane and latex.

[0014] Compared with the prior art, the present invention has the following advantages and beneficial effects: (1) The hydrogel coating prepared by the present invention can be firmly modified on the surface of medical catheters, has high interface bonding strength, and is suitable for most medical catheter materials; (2) The hydrogel coating prepared by the present invention has excellent lubrication ability and friction resistance, and the coating will not fall off after long-term cyclic friction; (3) The hydrogel coating prepared by the present invention has a long-lasting antibacterial property and a broad-spectrum antibacterial ability due to the synergistic effect of quaternary ammonium salt chitosan and zinc sulfate heptahydrate.

[0015] Specific implementation cases The present invention is further described in detail below in conjunction with specific examples, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art.

[0016] Example 1 (1) The polyvinyl chloride medical catheter was washed with deionized water and ethanol alternately three times to remove impurities on the surface of the polyvinyl chloride medical catheter, and then placed in an oven at a temperature of 40°C to dry; (2) immersing the polyvinyl chloride medical catheter obtained in step (1) in an aqueous polyurethane solution for 3 seconds, taking it out, and drying it in an oven at 40° C. to obtain a polyvinyl chloride medical catheter with an aqueous polyurethane layer coated on its surface; (3) 1 part by mass of methacrylate sulfobetaine, 2 parts by mass of N-vinyl pyrrolidone, 0.1 parts by mass of zinc sulfate heptahydrate, and 0.45 parts by mass of quaternary ammonium salt chitosan were uniformly dissolved in 10 parts by mass of deionized water, and then 0.005 parts by mass of N, N-methylenebisacrylamide and 0.01 parts by mass of I2959 were added, the mixture was stirred and mixed uniformly, and then ultrasonic treatment was performed to remove bubbles to obtain a pre-gel solution; (4) Immerse the polyvinyl chloride medical catheter obtained in step (2) in the pregel solution obtained in step (3) for 3 s, take the medical catheter out of the pregel solution, and illuminate it under a light intensity of 500 mW / cm 2 The polyvinyl chloride medical catheter was irradiated with ultraviolet light for 30 min to form a hydrophilic, lubricating and antibacterial hydrogel coating on its surface.

[0017] Example 2 (1) The polyvinyl chloride medical catheter was washed with deionized water and ethanol alternately three times to remove impurities on the surface of the polyvinyl chloride medical catheter, and then placed in an oven at a temperature of 50 °C to dry; (2) immersing the polyvinyl chloride medical catheter obtained in step (1) in an aqueous polyurethane solution for 3 seconds, taking it out, and drying it in an oven at a temperature of 50° C. to obtain a polyvinyl chloride medical catheter with a surface coated with an aqueous polyurethane layer; (3) 2 parts by mass of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonic acid propyl)ammonium hydroxide, 3 parts by mass of polyvinyl pyrrolidone, 0.15 parts by mass of zinc sulfate heptahydrate, and 0.5 parts by mass of quaternary ammonium salt chitosan were uniformly dissolved in 10 parts by mass of deionized water, and then 0.007 parts by mass of N, N-methylenebisacrylamide and 0.01 parts by mass of I2959 were added, stirred and mixed, and then ultrasonic treatment was performed to remove bubbles to obtain a pre-gel solution; (4) Immerse the polyvinyl chloride medical catheter obtained in step (2) in the pregel solution obtained in step (3) for 4 s, remove the medical catheter from the pregel solution, and illuminate it under a light intensity of 600 mW / cm 2 The polyvinyl chloride medical catheter was irradiated with ultraviolet light for 20 min to form a hydrophilic, lubricating and antibacterial hydrogel coating on its surface.

[0018] Example 3 (1) The polyvinyl chloride medical catheter was washed with deionized water and ethanol alternately three times to remove impurities on the surface of the polyvinyl chloride medical catheter, and then placed in an oven at a temperature of 50 °C to dry; (2) immersing the polyvinyl chloride medical catheter obtained in step (1) in an aqueous polyurethane solution for 4 seconds, taking it out, and drying it in an oven at a temperature of 50° C. to obtain a polyvinyl chloride medical catheter with a surface coated with an aqueous polyurethane layer; (3) 3 parts by mass of carboxybetaine methacrylate, 2 parts by mass of N-vinylpyrrolidone, 0.1 parts by mass of zinc sulfate heptahydrate, and 0.45 parts by mass of quaternary ammonium salt chitosan were uniformly dissolved in 12 parts by mass of deionized water, and then 0.007 parts by mass of polyethylene glycol dimethacrylate and 0.01 parts by mass of I2959 were added, the mixture was stirred and mixed uniformly, and then ultrasonic treatment was performed to remove bubbles to obtain a pre-gel solution; (4) Immerse the polyvinyl chloride medical catheter obtained in step (2) in the pregel solution obtained in step (3) for 5 s, take the medical catheter out of the pregel solution, and illuminate it under a light intensity of 600 mW / cm 2 The polyvinyl chloride medical catheter was irradiated with ultraviolet light for 30 min to form a hydrophilic, lubricating and antibacterial hydrogel coating on its surface.

[0019] Example 4 (1) The latex medical catheter was washed with deionized water and ethanol alternately three times to remove impurities on the surface of the latex medical catheter, and then placed in an oven at a temperature of 50°C to dry; (2) immersing the latex medical catheter obtained in step (1) in an aqueous polyurethane solution for 5 seconds, taking it out, and drying it in an oven at a temperature of 50° C. to obtain a latex medical catheter with a surface coated with an aqueous polyurethane layer; (3) 3 parts by weight of carboxybetaine methacrylate, 1 part by weight of N-vinyl pyrrolidone, 0.3 parts by weight of zinc sulfate heptahydrate, and 0.45 parts by weight of quaternary ammonium salt chitosan were uniformly dissolved in 12 parts by weight of deionized water, and then 0.015 parts by weight of polyethylene glycol dimethacrylate and 0.01 parts by weight of I2959 were added, the mixture was stirred and mixed, and then ultrasonic treatment was performed to remove bubbles to obtain a pre-gel solution; (4) Immerse the latex medical catheter obtained in step (2) in the pre-gel solution obtained in step (3) for 5 s, remove the medical catheter from the pre-gel solution, and illuminate it under a light intensity of 700 mW / cm 2 The latex medical catheter was irradiated with ultraviolet light for 20 min to form a hydrophilic, lubricating and antibacterial hydrogel coating on the surface.

[0020] Example 5 (1) The polyurethane medical catheter was washed with deionized water and ethanol alternately three times to remove impurities on the surface of the polyurethane medical catheter, and then placed in an oven at 60 °C to dry; (2) immersing the polyurethane medical catheter obtained in step (1) into an aqueous polyurethane solution for 5 seconds, taking it out, and drying it in an oven at 60° C. to obtain a polyurethane medical catheter with a surface coated with an aqueous polyurethane layer; (3) 1 part by weight of carboxybetaine methacrylate, 3 parts by weight of N-vinyl pyrrolidone, 0.2 parts by weight of zinc sulfate heptahydrate, and 0.5 parts by weight of quaternary ammonium salt chitosan were uniformly dissolved in 9 parts by weight of deionized water, and then 0.01 parts by weight of polyethylene glycol dimethacrylate and 0.01 parts by weight of I2959 were added, the mixture was stirred and mixed, and then ultrasonic treatment was performed to remove bubbles to obtain a pre-gel solution; (4) Immerse the polyurethane medical catheter obtained in step (2) in the pregel solution obtained in step (3) for 6 s, take the medical catheter out of the pregel solution, and illuminate it under a light intensity of 800 mW / cm 2 The polyurethane medical catheter was irradiated with ultraviolet light for 20 min to form a hydrophilic, lubricating and antibacterial hydrogel coating on the surface.

[0021] Example 6 (1) The polyurethane medical catheter was washed with deionized water and ethanol alternately three times to remove impurities on the surface of the polyurethane medical catheter, and then placed in an oven at 60 °C to dry; (2) immersing the polyurethane medical catheter obtained in step (1) into an aqueous polyurethane solution for 6 seconds, taking it out, and drying it in an oven at 60° C. to obtain a polyurethane medical catheter with a surface coated with an aqueous polyurethane layer; (3) 3 parts by weight of methacrylate sulfobetaine, 1 part by weight of polyvinyl pyrrolidone, 0.15 parts by weight of zinc sulfate heptahydrate, and 0.45 parts by weight of quaternary ammonium salt chitosan were uniformly dissolved in 11 parts by weight of deionized water, and then 0.008 parts by weight of N, N-methylenebisacrylamide and 0.015 parts by weight of I2959 were added, the mixture was stirred and mixed, and then ultrasonic treatment was performed to remove bubbles to obtain a pre-gel solution; (4) Immerse the polyurethane medical catheter obtained in step (2) in the pregel solution obtained in step (3) for 6 s, take the medical catheter out of the pregel solution, and illuminate it under a light intensity of 800 mW / cm 2 The polyurethane medical catheter was irradiated with ultraviolet light for 30 min to form a hydrophilic, lubricating and antibacterial hydrogel coating on the surface. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 Graphs showing water contact angles of the polyvinyl chloride medical catheter in Example 2, the polyvinyl chloride medical catheter coated with waterborne polyurethane, and the polyvinyl chloride medical catheter coated with a hydrogel coating.

Claims

1. A method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating, characterized in that: The steps include: (1) The medical catheter was washed three times with deionized water and ethanol alternately to remove impurities on the surface of the medical catheter, and then placed in an oven at a temperature of 40-60 °C to dry; (2) immersing the medical catheter obtained in step (1) into an aqueous polyurethane solution, taking it out, and drying it in an oven at a temperature of 40-60° C. to obtain a medical catheter with a surface coated with an aqueous polyurethane coating; (3) dissolving the zwitterionic monomer, nonionic compound, zinc sulfate heptahydrate and quaternary ammonium salt chitosan uniformly in deionized water, then adding a crosslinking agent and a photoinitiator, stirring uniformly and then performing ultrasonic treatment to remove bubbles to obtain a pre-gel solution; (4) Immersing the medical catheter obtained in step (2) into the pregel solution obtained in step (3), taking the medical catheter out of the pregel solution, and irradiating it under ultraviolet light, thereby forming a hydrophilic, lubricating, and antibacterial hydrogel coating on the surface of the medical catheter.

2. The method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating according to claim 1, characterized in that: The aqueous polyurethane solution is RM-2020PN aqueous polyurethane.

3. The method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating according to claim 1, characterized in that: The amount of the zwitterionic monomer is 1-3 parts by mass, the amount of the nonionic compound is 1-3 parts by mass, the amount of zinc sulfate heptahydrate is 0.05-0.2 parts by mass, the amount of quaternary ammonium salt chitosan is 0.4-0.5 parts by mass, the amount of deionized water is 8-12 parts by mass, the amount of the crosslinking agent is 0.005-0.01 parts by mass, and the amount of the photoinitiator is 0.01-0.02 parts by mass.

4. The method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating according to claim 1, characterized in that: The zwitterionic monomer is any one or more of methacrylate sulfobetaine, methacrylate carboxybetaine, and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonic acid propyl)ammonium hydroxide.

5. The method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating according to claim 1, characterized in that: The non-ionic compound is any one or more of N-vinyl pyrrolidone and polyvinyl pyrrolidone.

6. The method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating according to claim 1, characterized in that: The cross-linking agent is any one or more of polyethylene glycol dimethacrylate and N,N-methylenebisacrylamide.

7. The method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating according to claim 1, characterized in that: The photoinitiator is I2959.

8. The method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating according to claim 1, characterized in that: The medical catheter is immersed in the aqueous polyurethane solution for 3-6 s, and immersed in the pre-gel solution for 3-6 s.

9. The method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating according to claim 1, characterized in that: The light intensity of the ultraviolet light is 500-800 mW / cm 2 The irradiation time is 20-40 min.

10. The method for firmly modifying the surface of a medical catheter with a hydrophilic, lubricating, antibacterial hydrogel coating according to claim 1, characterized in that: The medical catheter is made of any one of polyvinyl chloride, polyethylene, polyurethane and latex.

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