An antibacterial coating for urinary catheters and a method for its preparation

Abstract

The application discloses an antibacterial coating for a urinary catheter and a preparation method thereof, and belongs to the technical field of antibacterial coatings. The antibacterial coating comprises the following raw materials in parts by weight: 55-70 parts of modified polyurethane, 5-10 parts of a curing agent, 5-10 parts of modified nano zinc oxide, 5-10 parts of an additive, and 70-80 parts of deionized water. The modified polyurethane, the modified nano zinc oxide and the additive are added into the deionized water, stirred uniformly, the curing agent is added, coated on the surface of the urinary catheter, and solidified to obtain the antibacterial coating. The antibacterial coating takes the modified polyurethane as a matrix, realizes organic / inorganic synergistic antibacterial through the antibacterial performance of the modified polyurethane itself and the nano zinc oxide, and gives the coating excellent antibacterial performance.

Description

Technical Field

[0001] This invention relates to the field of antibacterial coating technology, specifically to an antibacterial coating for urinary catheters and its preparation method. Background Technology

[0002] Catheter-related infections (CAIs) are among the most common hospital-acquired infections. Catheter-associated urinary tract infections (CAUTIs) are urinary tract infections that occur after a urinary catheter has been inserted or within 48 hours of its removal. Approximately 75% of hospital-acquired urinary tract infections (UTIs) are catheter-related, with a mortality rate of 7.3%. The urethral environment is highly conducive to bacterial colonization, leading to biofilm formation on the catheter surface and catheter-associated bacteriuria.

[0003] In recent years, modifying antibacterial coatings has become an important method for preventing urinary tract infections without affecting the mechanical performance of catheters. Antibacterial coatings can effectively kill bacteria and prevent bacterial accumulation on the catheter surface, thus preventing infection. However, bacterial colonization, adhesion, and biofilm formation on the catheter surface can easily cause the antibacterial coating to become ineffective, thus failing to provide long-term bactericidal protection. Therefore, improving the long-term antibacterial effect of the coating is crucial. Simultaneously, the mechanical strength of the catheter can easily cause damage to the urethral mucosa, making the lubricity of the coating also very important.

[0004] Chinese invention patent CN201431691A discloses an antibacterial hydrophilic coated urinary catheter. Its structure involves sequentially coating the outer surface of the catheter body with an antibacterial layer and a hydrophilic coating. The antibacterial coating contains chitin or chitosan and its derivatives, while the hydrophilic coating is made of polyethylene glycol, polyvinylpyrrolidone, or a polyvinylpyrrolidone-vinyl acetate hydrophilic polymer. This structure is simple and reasonable, facilitating both antibacterial and lubricating effects, and is easy to mass-produce and use. However, its antibacterial performance cannot be sustained for a long time. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides an antibacterial coating for urinary catheters and a method for preparing the same.

[0006] The objective of this invention can be achieved through the following technical solutions:

[0007] An antibacterial coating for urinary catheters comprises the following raw materials in parts by weight: 55-70 parts modified polyurethane, 5-10 parts curing agent, 5-10 parts modified nano zinc oxide, 5-10 parts additives, and 70-80 parts deionized water.

[0008] The modified polyurethane is prepared by the following steps:

[0009] Step S1: Add polytetrahydrofuran diol to a flask, purge with nitrogen, heat to 50°C and stir at a constant speed, add isophorone diisocyanate, keep warm and stir magnetically for 3 hours to obtain a prepolymer, then add dimethyl carbonate to reduce viscosity, continue stirring and react for 1 hour, cool to 45°C, add dibutyltin dilaurate and malic acid, continue stirring and react for 3 hours to obtain polymer a;

[0010] In step S1, polytetrahydrofuran diol is used as the soft segment, isophorone diisocyanate as the hard end, and 2,2-bis(hydroxymethyl)propionic acid is used as the chain extender. Under the action of the catalyst dibutyltin dilaurate, a polyurethane polymer containing carboxyl groups is prepared.

[0011] Step S2: Add compound a to tetrahydrofuran, add heparin, stir magnetically for 15 min, then add 4-dimethylaminopyridine and diisopropylcarbodiimide, stir and react in an ice-water bath for 4-6 h, then transfer to room temperature and continue stirring for 4 h, filter, and vacuum dry to obtain modified polyurethane.

[0012] In step S2, the carboxyl group introduced into compound a under the action of 4-dimethylaminopyridine and diisopropylcarbodiimide can react with the hydroxyl group on the heparin structure, thereby grafting heparin into the polyurethane structure to obtain modified polyurethane. When made into a coating, the heparin in the modified polyurethane can inhibit bacterial adhesion.

[0013] Furthermore, in step S1, the ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate, and malic acid is controlled to be 10-15g: 4-5mL: 25-30mL: 1.5-2mL, and the amount of dibutyltin dilaurate is 0.1-0.3% of the weight of polytetrahydrofuran diol.

[0014] Further, in step S2, the weight ratio of compound a, heparin, 4-dimethylaminopyridine, diisopropylcarbodiimide and tetrahydrofuran is controlled to be 10-15:1:0.1-0.2:0.3-0.4:20-25.

[0015] Furthermore, the modified nano zinc oxide is prepared by surface modification with silane coupling agent KH550.

[0016] Furthermore, the additive is a mixture of wetting agent and leveling agent in a weight ratio of 1:5.

[0017] Furthermore, the wetting agent is one or more of alkyl sulfates, fatty acids, fatty acid ester sulfates and carboxylic acid soaps mixed in any proportion.

[0018] Furthermore, the leveling agent is polydimethylsiloxane or polymethylphenylsiloxane.

[0019] Furthermore, the curing agent is one or more of ethylenediamine, diethylenetriamine and triethylenetetramine mixed in any proportion.

[0020] A method for preparing an antibacterial coating for urinary catheters includes the following steps:

[0021] Modified polyurethane, modified nano zinc oxide, and additives were added to deionized water, stirred evenly, and then a curing agent was added. The mixture was then coated onto the surface of a urinary catheter and cured to obtain an antibacterial coating.

[0022] The beneficial effects of this invention are:

[0023] This invention prepares an antibacterial coating for urinary catheters. The antibacterial coating uses modified polyurethane as a matrix. The antibacterial properties introduced by the modified polyurethane itself, combined with nano-zinc oxide, achieve organic / inorganic synergistic antibacterial effects, giving the coating excellent antibacterial properties. In the preparation of this modified polyurethane, polytetrahydrofuran diol is used as the soft segment, isophorone diisocyanate as the hard segment, and 2,2-bis(hydroxymethyl)propionic acid as the chain extender. Under the action of the catalyst dibutyltin dilaurate, a polyurethane polymer containing carboxyl groups, a polymer a, is prepared. Subsequently, under the action of 4-dimethylaminopyridine and diisopropylcarbodiimide, the carboxyl groups introduced in compound a can react with the hydroxyl groups on the heparin structure, thereby grafting heparin into the polyurethane structure to obtain the modified polyurethane. When made into a coating, the heparin in the modified polyurethane can inhibit bacterial adhesion. Furthermore, by modifying the nano-zinc oxide with KH550 and then attaching amino groups to the surface of the nano-zinc oxide, it can react with the carboxyl groups on the heparin, improving the binding affinity between the nano-zinc oxide and the matrix. Detailed Implementation

[0024] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] Example 1: An antibacterial coating for urinary catheters, comprising the following raw materials in parts by weight: 55 parts modified polyurethane, 5 parts curing agent, 5 parts modified nano zinc oxide, 5 parts additives, and 70 parts deionized water;

[0026] A method for preparing an antibacterial coating for urinary catheters includes the following steps:

[0027] Modified polyurethane, modified nano zinc oxide, and additives were added to deionized water, stirred evenly, and then a curing agent was added. The mixture was then coated onto the surface of a urinary catheter and cured to obtain an antibacterial coating.

[0028] The modified polyurethane is prepared by the following steps:

[0029] Step S1: Add polytetrahydrofuran diol to a flask, purge with nitrogen, heat to 50°C and stir at a constant speed, add isophorone diisocyanate, keep warm and stir magnetically for 3 hours to obtain a prepolymer, then add dimethyl carbonate to reduce viscosity, continue stirring and react for 1 hour, cool to 45°C, add dibutyltin dilaurate and malic acid, continue stirring and react for 3 hours to obtain polymer a. Control the ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate and malic acid to 10g:4mL:25mL:1.5mL, and the amount of dibutyltin dilaurate is 0.1% of the weight of polytetrahydrofuran diol;

[0030] Step S2: Add compound a to tetrahydrofuran, add heparin, stir magnetically for 15 min, then add 4-dimethylaminopyridine and diisopropylcarbodiimide, stir and react in an ice-water bath for 4 h, then transfer to room temperature and continue stirring for 4 h, filter, and vacuum dry to obtain modified polyurethane. Control the weight ratio of compound a, heparin, 4-dimethylaminopyridine, diisopropylcarbodiimide and tetrahydrofuran to be 10:1:0.1:0.3:20.

[0031] The modified nano zinc oxide was prepared by surface modification with silane coupling agent KH550.

[0032] The additive is a mixture of wetting agent and leveling agent in a weight ratio of 1:5.

[0033] The wetting agent is an alkyl sulfate.

[0034] The leveling agent is polydimethylsiloxane.

[0035] The curing agent is ethylenediamine.

[0036] Example 2: An antibacterial coating for urinary catheters, comprising the following raw materials in parts by weight: 60 parts modified polyurethane, 8 parts curing agent, 8 parts modified nano zinc oxide, 8 parts additives, and 75 parts deionized water;

[0037] A method for preparing an antibacterial coating for urinary catheters includes the following steps:

[0038] Modified polyurethane, modified nano zinc oxide, and additives were added to deionized water, stirred evenly, and then a curing agent was added. The mixture was then coated onto the surface of a urinary catheter and cured to obtain an antibacterial coating.

[0039] The modified polyurethane is prepared by the following steps:

[0040] Step S1: Add polytetrahydrofuran diol to a flask, purge with nitrogen, heat to 50°C and stir at a constant speed, add isophorone diisocyanate, keep warm and stir magnetically for 3 hours to obtain a prepolymer, then add dimethyl carbonate to reduce viscosity, continue stirring and react for 1 hour, cool to 45°C, add dibutyltin dilaurate and malic acid, continue stirring and react for 3 hours to obtain polymer a. Control the ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate and malic acid to 12g:4.5mL:28mL:1.8mL, and the amount of dibutyltin dilaurate is 0.2% of the weight of polytetrahydrofuran diol;

[0041] Step S2: Add compound a to tetrahydrofuran, add heparin, stir magnetically for 15 min, then add 4-dimethylaminopyridine and diisopropylcarbodiimide, stir and react in an ice-water bath for 5 h, then transfer to room temperature and continue stirring for 4 h, filter, and vacuum dry to obtain modified polyurethane. Control the weight ratio of compound a, heparin, 4-dimethylaminopyridine, diisopropylcarbodiimide and tetrahydrofuran to be 12:1:0.1:0.3:22.

[0042] The modified nano zinc oxide was prepared by surface modification with silane coupling agent KH550.

[0043] The additive is a mixture of wetting agent and leveling agent in a weight ratio of 1:5.

[0044] The wetting agent is a fatty acid.

[0045] The leveling agent is polymethylphenylsiloxane.

[0046] The curing agent is diethylenetriamine.

[0047] Example 3: An antibacterial coating for urinary catheters, comprising the following raw materials in parts by weight: 70 parts modified polyurethane, 10 parts curing agent, 10 parts modified nano zinc oxide, 10 parts additives, and 80 parts deionized water;

[0048] A method for preparing an antibacterial coating for urinary catheters includes the following steps:

[0049] Modified polyurethane, modified nano zinc oxide, and additives were added to deionized water, stirred evenly, and then a curing agent was added. The mixture was then coated onto the surface of a urinary catheter and cured to obtain an antibacterial coating.

[0050] The modified polyurethane is prepared by the following steps:

[0051] Step S1: Add polytetrahydrofuran diol to a flask, purge with nitrogen, heat to 50°C and stir at a constant speed, add isophorone diisocyanate, keep warm and stir magnetically for 3 hours to obtain a prepolymer, then add dimethyl carbonate to reduce viscosity, continue stirring and react for 1 hour, cool to 45°C, add dibutyltin dilaurate and malic acid, continue stirring and react for 3 hours to obtain polymer a, control the ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate and malic acid to be 15g:5mL:30mL:2mL, and the amount of dibutyltin dilaurate is 0.3% of the weight of polytetrahydrofuran diol;

[0052] Step S2: Add compound a to tetrahydrofuran, add heparin, stir magnetically for 15 min, then add 4-dimethylaminopyridine and diisopropylcarbodiimide, stir and react in an ice-water bath for 6 h, then transfer to room temperature and continue stirring for 4 h, filter, and vacuum dry to obtain modified polyurethane. Control the weight ratio of compound a, heparin, 4-dimethylaminopyridine, diisopropylcarbodiimide and tetrahydrofuran to be 15:1:0.2:0.4:25.

[0053] The modified nano zinc oxide was prepared by surface modification with silane coupling agent KH550.

[0054] The additive is a mixture of wetting agent and leveling agent in a weight ratio of 1:5.

[0055] The wetting agent is a fatty acid ester sulfate.

[0056] The leveling agent is polymethylphenylsiloxane.

[0057] The curing agent is triethylenetetramine.

[0058] Biological tests were conducted on the antibacterial coatings for urinary catheters prepared in Examples 1-3;

[0059] 1. Acute systemic toxicity

[0060] This experiment was conducted in accordance with the national standard GB / T16886.11-2011 "Biological evaluation of medical devices - Part 11: Systemic toxicity test" to perform acute systemic toxicity tests on the test samples of 0.9% sodium chloride injection (SC) and cottonseed oil (CSO).

[0061] The test samples were extracted using SC and CSO and administered to the test animals via intraperitoneal injection (IP). The condition of all animals and the number of deaths were observed and recorded immediately after injection, at 4 h, 24 h, 48 h, and 72 h post-injection. All animals were weighed at 24 h, 48 h, and 72 h post-injection, and the weight was recorded.

[0062] Under the conditions of this experiment, no animals in either the experimental or control groups died, no mice showed signs of poisoning, and all mice showed an increase in weight. The results indicate that the antibacterial coating test solution for urinary catheters in this embodiment did not cause acute systemic effects in the experimental mice.

[0063] 2. Cytotoxicity test

[0064] This study used in vitro cell culture methods for toxicological risk assessment. The experiment was conducted according to the MTT assay specified in the national standard GB / T16886.5-2017, "Biological Evaluation of Medical Devices - Part 5: In Vitro Cytotoxicity Tests".

[0065] The sample test solution, the extracts of the negative control and positive control, and the medium control were placed in six wells of a cell culture plate containing L929 mouse fibroblasts. The cells were cultured in a 5% CO2, 37°C cell culture incubator. After 24 hours, the morphological changes of the cells in the sample group, negative control group, positive control group, and medium control group were observed under a microscope. The cell viability of each test group (sample group, negative control group, positive control group) relative to the medium control group was determined by the MTT assay.

[0066] Under the conditions of this experiment, the cell viability of the antibacterial coating test solutions for urinary catheters in Examples 1-3 was in the range of 81-90%, with no potential cytotoxicity. (Reference standard: a viability rate of less than 70% indicates potential toxicity.)

[0067] 3. Skin sensitization test

[0068] This experiment was conducted in accordance with the national standard GB / T16886.10-2017 "Biological evaluation of medical devices - Part 10: Irritation and skin sensitization test". The maximum dose test for skin sensitization of the test samples 0.9% sodium chloride injection (SC) and cottonseed oil (CSO) was carried out to evaluate the potential of the test samples to induce skin sensitization in guinea pigs under the test conditions.

[0069] SC and CSO were used to extract the test samples. Each test solution was injected intradermally and fixed to the shaved area on the back of the experimental group guinea pigs to induce skin sensitization. After the induction period, filter paper soaked in the test solution was fixed to the shaved area on the abdomen of the experimental group animals for 24 hours to stimulate the skin. The skin condition at all stimulation sites was observed and recorded at 24 and 48 hours after the filter paper was removed, and described and graded according to the Magnusson and Kligman grading system. The same procedure was performed on the control group animals.

[0070] Under the conditions of this experiment, the antibacterial coating test solution for urinary catheters in Examples 1-3 did not cause skin sensitization reactions in guinea pigs.

[0071] Comparative Example 1: Compared with Example 1, this comparative example did not include heparin in the preparation of the modified polyurethane. The preparation method is as follows:

[0072] Modified polyurethane is prepared through the following steps:

[0073] Polytetrahydrofuran diol was added to a flask, nitrogen gas was introduced, and the temperature was raised to 50°C with uniform stirring. Isophorone diisocyanate was added, and the mixture was kept at this temperature and magnetically stirred for 3 hours to obtain a prepolymer. Then, dimethyl carbonate was added to reduce the viscosity, and the mixture was stirred and reacted for 1 hour. The temperature was lowered to 45°C, and dibutyltin dilaurate and malic acid were added. The mixture was stirred and reacted for 3 hours to obtain a modified polyurethane. The ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate, and malic acid was controlled to be 10 g: 4 mL: 25 mL: 1.5 mL, and the amount of dibutyltin dilaurate was 0.1% of the weight of polytetrahydrofuran diol.

[0074] The rest is the same as in Example 1.

[0075] The antibacterial properties of the antibacterial coatings prepared in Examples 1-3 and Comparative Example 1 were tested, and the results are shown in Table 1 below:

[0076] Antibacterial test: The model bacteria selected were Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The procedure was as follows: Staphylococcus aureus and Escherichia coli were activated and amplified, and then diluted to a concentration of 5 × 10⁻⁶. 5 A bacterial suspension of CFU / mL was prepared. 200 μL of the suspension was taken with a sterile pipette and evenly spread on the surface of each sample. The samples were then incubated at 37°C for 24 h. The bacteria on the sample surface were then washed off with an equal volume of culture medium and incubated at 37°C for another 8 h. The samples were then diluted, plated, and the colony count of each group was counted and the inhibition rate was calculated.

[0077] Table 1

[0078]

[0079] As can be seen from Table 1 above, the antibacterial coatings prepared in Examples 1-3 of the present invention have excellent antibacterial properties.

[0080] The above description is merely an example and illustration of the concept of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described or use similar methods to replace them, as long as they do not deviate from the concept of the invention or exceed the scope defined in the claims, they should all fall within the protection scope of the present invention.

Claims

1. An antibacterial coating for urinary catheters, characterized in that, The raw materials include the following parts by weight: 55-70 parts modified polyurethane, 5-10 parts curing agent, 5-10 parts modified nano zinc oxide, 5-10 parts additives, and 70-80 parts deionized water. The modified polyurethane is prepared by the following steps: Step S1: Add polytetrahydrofuran diol to a flask, purge with nitrogen, heat to 50°C and stir at a constant speed, add isophorone diisocyanate, keep warm and stir magnetically for 3 hours to obtain a prepolymer, then add dimethyl carbonate to reduce viscosity, continue stirring and react for 1 hour, cool to 45°C, add dibutyltin dilaurate and malic acid, continue stirring and react for 3 hours to obtain polymer a; Step S2: Add compound a to tetrahydrofuran, add heparin, stir magnetically for 15 min, then add 4-dimethylaminopyridine and diisopropylcarbodiimide, stir and react in an ice-water bath for 4-6 h, then transfer to room temperature and continue stirring for 4 h, filter, and vacuum dry to obtain modified polyurethane. In step S1, the ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate, and malic acid is controlled to be 10-15g: 4-5mL: 25-30mL: 1.5-2mL, and the amount of dibutyltin dilaurate is 0.1-0.3% of the weight of polytetrahydrofuran diol. In step S2, the weight ratio of compound a, heparin, 4-dimethylaminopyridine, diisopropylcarbodiimide and tetrahydrofuran is controlled to be 10-15:1:0.1-0.2:0.3-0.4:20-25; The modified nano zinc oxide was prepared by surface modification with silane coupling agent KH550.

2. The antibacterial coating for a urinary catheter according to claim 1, characterized in that, The additive is a mixture of wetting agent and leveling agent in a weight ratio of 1:

5.

3. The antibacterial coating for a urinary catheter according to claim 2, characterized in that, The wetting agent is one or more of alkyl sulfates, fatty acids, fatty acid ester sulfates and carboxylic acid soaps mixed in any proportion.

4. The antibacterial coating for a urinary catheter according to claim 2, characterized in that, The leveling agent is polydimethylsiloxane or polymethylphenylsiloxane.

5. The antibacterial coating for a urinary catheter according to claim 1, characterized in that, The curing agent is one or more of ethylenediamine, diethylenetriamine and triethylenetetramine mixed in any proportion.

6. The method for preparing an antibacterial coating for a urinary catheter according to claim 1, characterized in that, Includes the following steps: Modified polyurethane, modified nano zinc oxide, and additives were added to deionized water, stirred evenly, and then a curing agent was added. The mixture was then coated onto the surface of a urinary catheter and cured to obtain an antibacterial coating.

Images