Antibacterial coating for catheter and preparation method thereof

Abstract

The invention discloses an antibacterial coating for a catheter and a preparation method thereof, and belongs to the technical field of antibacterial coatings, the antibacterial coating comprises the following raw materials 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 auxiliary agent, and 70-80 parts of deionized water; and adding the modified polyurethane, the modified nano zinc oxide and an auxiliary agent into deionized water, uniformly stirring, adding a curing agent, coating the surface of the catheter with the obtained mixture, and curing to obtain the antibacterial coating. According to the antibacterial coating, modified polyurethane is used as a matrix, and the antibacterial property introduced by the modified polyurethane is cooperated with nano-zinc oxide, so that organic / inorganic synergistic antibacterial is realized, and the coating is endowed with excellent antibacterial property.

Description

Technical Field

[0001] The invention relates to the technical field of antibacterial coatings, and in particular to an antibacterial coating for a urinary catheter and a preparation method thereof. Background Art

[0002] Catheter-associated infection (CAI) is one of the most common nosocomial infections. Catheter-associated urinary tract infection (CAUTI) refers to a urinary tract infection that occurs in patients with an indwelling urinary catheter or within 48 hours of catheter removal. Among hospital-acquired urinary tract infections (UTIs), approximately 75% of the incidence is related to the catheter, and the mortality rate is as high as 7.3%. The urinary tract environment is very conducive to bacterial colonization, resulting in biofilm formation on the catheter surface and the formation of catheter-associated bacteriuria.

[0003] In recent years, modified antibacterial coatings have become an important method for preventing urinary tract infections without affecting the mechanical properties of catheters. Antibacterial coatings can effectively kill bacteria and prevent bacteria from gathering on the surface of the catheter to cause infection. However, the colonization and adhesion of bacteria on the surface of the catheter to form a biofilm can easily make the antibacterial coating ineffective, making it unable to effectively kill bacteria in the long term. Therefore, it is very important to improve the long-term antibacterial effect of the coating. At the same time, the mechanical strength of the catheter can easily cause damage to the urethral mucosa, and the lubricity of the coating is also of great significance.

[0004] Chinese invention patent CN201431691A discloses an antibacterial hydrophilic coating catheter, which has a structure in which an antibacterial layer and a hydrophilic coating are sequentially coated on the outer surface of the catheter body, wherein the antibacterial coating is a coating containing components such as chitin or chitosan and its derivatives, and the hydrophilic coating is a coating of polyethylene glycol, polyvinyl pyrrolidone or polyvinyl pyrrolidone-vinyl acetate hydrophilic polymer. The structural design is simple and reasonable, which is convenient for exerting its dual functions of antibacterial and lubrication, easy for large-scale production, and convenient for use and operation. However, its antibacterial performance cannot achieve long-term effectiveness. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides an antibacterial coating for a urinary catheter and a preparation method thereof.

[0006] The purpose of the present invention can be achieved through the following technical solutions:

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

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

[0009] Step S1, adding polytetrahydrofuran diol into a flask, introducing nitrogen, heating to 50° C. and stirring at a uniform speed, adding isophorone diisocyanate, keeping warm and magnetically stirring for 3 hours to obtain a prepolymer, then adding dimethyl carbonate to reduce the viscosity, continuing stirring and reacting for 1 hour, cooling to 45° C., adding dibutyltin dilaurate and malic acid, continuing stirring and reacting for 3 hours to obtain a polymer a;

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

[0011] Step S2, adding compound a to tetrahydrofuran, adding heparin, adding 4-dimethylaminopyridine and diisopropylcarbodiimide after magnetic stirring for 15 minutes, stirring and reacting for 4-6 hours under an ice-water bath, then transferring to room temperature and continuing stirring for 4 hours, filtering, and vacuum drying to obtain a 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 and then graft the heparin into the polyurethane structure to obtain a modified polyurethane. When the modified polyurethane is made into a coating, the heparin in the modified polyurethane can inhibit bacterial attachment.

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

[0014] Furthermore, 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 auxiliary agent is a mixture of a wetting agent and a leveling agent in a weight ratio of 1:5.

[0017] Furthermore, the wetting agent is a mixture of one or more of alkyl sulfates, fatty acids, fatty acid ester sulfates and carboxylic acid soaps 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 a urinary catheter comprises the following steps:

[0021] The modified polyurethane, modified nano zinc oxide and auxiliary agent are added into deionized water, stirred evenly, a curing agent is added, coated on the surface of the catheter, and cured to obtain an antibacterial coating.

[0022] Beneficial effects of the present invention:

[0023] The invention prepares an antibacterial coating for a urinary catheter. The antibacterial coating takes modified polyurethane as a matrix, and realizes organic / inorganic synergistic antibacterial through the antibacterial property introduced by the modified polyurethane itself and nano zinc oxide, thereby giving the coating excellent antibacterial property. In the preparation process, the modified polyurethane takes polytetrahydrofuran diol as a soft segment, isophorone diisocyanate as a hard end, and 2,2-bis(hydroxymethyl)propionic acid as a chain extender. Under the action of a catalyst dibutyltin dilaurate, a polymer a containing a carboxyl group is prepared, which is a polyurethane polymer. Subsequently, under the action of 4-dimethylaminopyridine and diisopropylcarbodiimide, the carboxyl group introduced into the compound a can react with a hydroxyl group on a heparin structure, thereby grafting the heparin into the polyurethane structure, thereby preparing the modified polyurethane. After the coating is prepared, the heparin in the modified polyurethane can inhibit bacterial attachment. In addition, the nano zinc oxide is modified by KH550, and amino groups are connected to the surface of the nano zinc oxide, which can react with the carboxyl group on the heparin, thereby improving the binding property of the nano zinc oxide with the matrix. DETAILED DESCRIPTION

[0024] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

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

[0026] A method for preparing an antibacterial coating for a urinary catheter comprises the following steps:

[0027] The modified polyurethane, modified nano zinc oxide and auxiliary agent are added into deionized water, stirred evenly, a curing agent is added, coated on the surface of the catheter, and cured to obtain an antibacterial coating.

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

[0029] Step S1, adding polytetrahydrofuran diol into a flask, introducing nitrogen, heating to 50° C. and stirring at a uniform speed, adding isophorone diisocyanate, keeping warm and magnetically stirring for 3 hours to obtain a prepolymer, then adding dimethyl carbonate to reduce the viscosity, continuing stirring and reacting for 1 hour, cooling to 45° C., adding dibutyltin dilaurate and malic acid, continuing stirring and reacting for 3 hours to obtain a polymer a, controlling the amount ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate and malic acid to be 10g:4mL:25mL:1.5mL, and the amount of dibutyltin dilaurate is 0.1% of the weight of polytetrahydrofuran diol;

[0030] Step S2, adding compound a to tetrahydrofuran, adding heparin, adding 4-dimethylaminopyridine and diisopropylcarbodiimide after magnetic stirring for 15 minutes, stirring and reacting for 4 hours in an ice-water bath, then transferring to room temperature and continuing stirring for 4 hours, filtering, and vacuum drying to obtain a modified polyurethane, wherein the weight ratio of compound a, heparin, 4-dimethylaminopyridine, diisopropylcarbodiimide and tetrahydrofuran is controlled to be 10:1:0.1:0.3:20.

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

[0032] The auxiliary agent is a mixture of a wetting agent and a 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 a urinary catheter, comprising the following raw materials in parts by weight: 60 parts of modified polyurethane, 8 parts of curing agent, 8 parts of modified nano zinc oxide, 8 parts of auxiliary agent, and 75 parts of deionized water;

[0037] A method for preparing an antibacterial coating for a urinary catheter comprises the following steps:

[0038] The modified polyurethane, modified nano zinc oxide and auxiliary agent are added into deionized water, stirred evenly, a curing agent is added, coated on the surface of the catheter, and cured to obtain an antibacterial coating.

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

[0040] Step S1, adding polytetrahydrofuran diol into a flask, introducing nitrogen, heating to 50° C. and stirring at a uniform speed, adding isophorone diisocyanate, keeping warm and magnetically stirring for 3 hours to obtain a prepolymer, then adding dimethyl carbonate to reduce the viscosity, continuing stirring and reacting for 1 hour, cooling to 45° C., adding dibutyltin dilaurate and malic acid, continuing stirring and reacting for 3 hours to obtain a polymer a, controlling the amount ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate and malic acid to be 12 g: 4.5 mL: 28 mL: 1.8 mL, and the amount of dibutyltin dilaurate is 0.2% of the weight of polytetrahydrofuran diol;

[0041] Step S2, adding compound a to tetrahydrofuran, adding heparin, adding 4-dimethylaminopyridine and diisopropylcarbodiimide after magnetic stirring for 15 minutes, stirring and reacting in an ice-water bath for 5 hours, then transferring to room temperature and continuing stirring for 4 hours, filtering, and vacuum drying to obtain a modified polyurethane, wherein the weight ratio of compound a, heparin, 4-dimethylaminopyridine, diisopropylcarbodiimide and tetrahydrofuran is controlled to be 12:1:0.1:0.3:22.

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

[0043] The auxiliary agent is a mixture of a wetting agent and a 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 a urinary catheter, comprising the following raw materials in parts by weight: 70 parts of modified polyurethane, 10 parts of curing agent, 10 parts of modified nano zinc oxide, 10 parts of auxiliary agent, and 80 parts of deionized water;

[0048] A method for preparing an antibacterial coating for a urinary catheter comprises the following steps:

[0049] The modified polyurethane, modified nano zinc oxide and auxiliary agent are added into deionized water, stirred evenly, a curing agent is added, coated on the surface of the catheter, and cured to obtain an antibacterial coating.

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

[0051] Step S1, adding polytetrahydrofuran diol into a flask, introducing nitrogen, heating to 50° C. and stirring at a uniform speed, adding isophorone diisocyanate, keeping warm and magnetically stirring for 3 hours to obtain a prepolymer, then adding dimethyl carbonate to reduce the viscosity, continuing stirring and reacting for 1 hour, cooling to 45° C., adding dibutyltin dilaurate and malic acid, continuing stirring and reacting for 3 hours to obtain a polymer a, controlling the amount 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, adding compound a to tetrahydrofuran, adding heparin, adding 4-dimethylaminopyridine and diisopropylcarbodiimide after magnetic stirring for 15 minutes, stirring and reacting for 6 hours in an ice-water bath, then transferring to room temperature and continuing stirring for 4 hours, filtering, and vacuum drying to obtain a modified polyurethane, wherein the weight ratio of compound a, heparin, 4-dimethylaminopyridine, diisopropylcarbodiimide and tetrahydrofuran is controlled to be 15:1:0.2:0.4:25.

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

[0054] The auxiliary agent is a mixture of a wetting agent and a 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 performed on the antibacterial coatings for urinary catheters prepared in Examples 1-3;

[0059] 1. Acute systemic toxicity

[0060] This test was conducted in accordance with the national standard GB / T16886.112011 "Biological Evaluation of Medical Devices Part 11: Systemic Toxicity Test" method, and the 0.9% sodium chloride injection (SC) and cottonseed oil (CSO) sample test solutions of the test samples were subjected to acute systemic toxicity tests in mice.

[0061] The test samples were extracted with SC and CSO and given to the test animals by intraperitoneal injection (IP); the status of all animals and the number of dead animals were observed and recorded immediately, 4h, 24h, 48h and 72h after injection. All animals were weighed and recorded 24h, 48h and 72h after injection.

[0062] Under the test conditions, no animals in the test group and the control group died, no test mice showed any symptoms of poisoning, and the weight of the mice increased. The test results show that the antibacterial coating test solution for urinary catheters in this embodiment has no acute systemic effect on the test mice.

[0063] 2. Cytotoxicity test

[0064] This test uses in vitro cell culture method to conduct toxicological risk assessment. This test is carried out according to the MTT method of the national standard GB / T16886.5-2017 "Biological Evaluation of Medical Devices Part 5: In Vitro Cytotoxicity Test".

[0065] The sample test solution, the extracts of the negative control and positive control, and the medium control were placed in 6 wells of a cell culture plate cultured with L929 mouse fibroblasts, and cultured in a 5% CO2, 37°C cell culture incubator. After 24 hours, the cell morphological changes of the test sample group, negative control group, positive control group, and medium control group after culture were observed under a microscope, and the cell survival rate of each test sample group, negative control group, positive control group relative to the medium control group was determined by the MTT method.

[0066] Under the test conditions, the cell survival rate of the antibacterial coating test solution for urinary catheters in Examples 1-3 is in the range of 81-90%, with no potential cytotoxicity. (Reference standard: if the survival rate is less than 70%, it is potentially toxic)

[0067] 3. Skin sensitization test

[0068] This test was conducted in accordance with the national standard GB / T16886.10-2017 "Biological Evaluation of Medical Devices Part 10: Irritation and Skin Sensitization Tests". The maximum skin sensitization dose test was conducted on the test samples of 0.9% sodium chloride injection (SC) and cottonseed oil (CSO) test solution to evaluate the potential of the test samples to cause skin sensitization reactions in guinea pigs under the test conditions.

[0069] The test samples were extracted using SC and CSO. Each test solution was intradermally injected and fixed on the shaved area on the back of the guinea pigs in the test group to induce skin sensitization; after the induction period, the filter paper soaked with the test solution was fixed on the shaved area on the abdomen of the animals in the test group for 24 hours. The skin conditions of all animals at the stimulating site were observed and recorded 24 hours and 48 hours after the filter paper was removed, and described and graded according to the Magnusson and Kligman grading standards. The control group animals were operated in the same way.

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

[0071] Comparative Example 1: Compared with Example 1, in this comparative example, heparin was not added during the preparation of the modified polyurethane, and the preparation method is as follows:

[0072] Modified polyurethane is made by the following steps:

[0073] Add polytetrahydrofuran diol into a flask, introduce nitrogen, heat to 50°C and stir at a uniform speed, add isophorone diisocyanate, keep warm and stir magnetically for 3 hours to obtain a prepolymer, then add dimethyl carbonate to reduce the 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 a modified polyurethane, and control the dosage ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate and malic acid to 10g:4mL:25mL:1.5mL, and the dosage of dibutyltin dilaurate is 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: Gram-positive bacteria: Staphylococcus aureus; Gram-negative bacteria: Escherichia coli were selected as model bacteria. The operation method is as follows: Staphylococcus aureus and Escherichia coli were activated and amplified, and then diluted to a concentration of 5×10 5 CFU / mL bacterial suspension, use a sterile pipette to take 200μL of the bacterial suspension and evenly spread it on the surface of each sample, and culture it at 37℃ for 24h; then use an equal volume of culture medium to blow off the bacteria on the surface of the sample, culture it at 37℃ for another 8h, spread it on the plate after dilution, count the number of colonies in each group of samples and calculate the inhibition rate.

[0077] Table 1

[0078]

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

[0080] The above contents are merely examples and explanations of the concept of the present invention. The technicians in this technical field may make various modifications or additions to the specific embodiments described or replace them in a similar manner. As long as they do not deviate from the concept of the invention or exceed the scope defined by the claims, they should all fall within the protection scope of the present invention.

Claims

1. An antibacterial coating for a urinary catheter, characterized in that: The invention comprises the following raw materials in parts by weight: 55-70 parts of modified polyurethane, 5-10 parts of curing agent, 5-10 parts of modified nano zinc oxide, 5-10 parts of auxiliary agent, and 70-80 parts of deionized water; The modified polyurethane is prepared by the following steps: Step S1, adding polytetrahydrofuran diol into a flask, introducing nitrogen, heating to 50° C. and stirring at a uniform speed, adding isophorone diisocyanate, keeping warm and magnetically stirring for 3 hours to obtain a prepolymer, then adding dimethyl carbonate to reduce the viscosity, continuing stirring and reacting for 1 hour, cooling to 45° C., adding dibutyltin dilaurate and malic acid, continuing stirring and reacting for 3 hours to obtain a polymer a; Step S2, adding compound a to tetrahydrofuran, adding heparin, adding 4-dimethylaminopyridine and diisopropylcarbodiimide after magnetic stirring for 15 minutes, stirring and reacting for 4-6 hours under an ice-water bath, then transferring to room temperature and continuing stirring for 4 hours, filtering, and vacuum drying to obtain a modified polyurethane.

2. The antibacterial coating for a urinary catheter according to claim 1, characterized in that: In step S1, the dosage ratio of polytetrahydrofuran diol, isophorone diisocyanate, dimethyl carbonate and malic acid is controlled to be 10-15 g: 4-5 mL: 25-30 mL: 1.5-2 mL, and the dosage of dibutyltin dilaurate is 0.1-0.3% of the weight of polytetrahydrofuran diol.

3. The antibacterial coating for a urinary catheter according to claim 1, characterized in that: 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.

4. The antibacterial coating for a urinary catheter according to claim 1, characterized in that: The modified nano zinc oxide is prepared by surface modification with silane coupling agent KH550.

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

5.

6. The antibacterial coating for a urinary catheter according to claim 5, characterized in that: The wetting agent is a mixture of one or more of alkyl sulfates, fatty acids, fatty acid ester sulfates and carboxylic acid soaps in any proportion.

7. The antibacterial coating for a urinary catheter according to claim 5, characterized in that: The leveling agent is polydimethylsiloxane or polymethylphenylsiloxane.

8. 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.

9. The method for preparing an antibacterial coating for a urinary catheter according to claim 1, characterized in that: The steps include: The modified polyurethane, modified nano zinc oxide and auxiliary agent are added into deionized water, stirred evenly, a curing agent is added, coated on the surface of the catheter, and cured to obtain an antibacterial coating.

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