An antibacterial and anti-adhesion medical catheter with excellent biocompatibility and a preparation method thereof
Patent Information
- Application Number
- CN202410029999.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-01-09
- Publication Date
- 2026-08-21
- Estimated Expiration
- 2044-01-09
AI Technical Summary
综上，研究结果表明介孔二氧化硅负载抗菌肽在药物传递和释放方面可以发挥出优异的效果，同时抗菌肽作为广谱抗菌剂展现出良好的抗菌效果，但介孔二氧化硅负载多肽通常以粒子形式发挥作用，目前还没有基于导管材料表面修饰二氧化硅-抗菌肽应用于医疗抗菌、抗粘附领域的相关报道
[0018]步骤6)所述的粘结剂为聚二甲基硅氧烷(PDMS)、聚偏氟乙烯(PVDF)、聚四氟乙烯(PTFE)中的一种，溶剂为正己烷、环己烷、二氯甲烷中的一种；后续处理每厘米长的导管表面喷涂粘结剂溶液的体积为0.5～2mL，喷涂SiO2@AMPs溶液的体积为1～5mL。
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Figure CN117838934B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedical antibacterial materials, specifically relating to an antibacterial and anti-adhesion medical catheter with excellent biocompatibility and its preparation method. Background Technology
[0002] In recent years, biomedical materials have played a crucial role in clinical applications, disease treatment, and healthy living. Among them, medical catheters, as a medium connecting the human body to the external environment, are widely used in gas and liquid delivery and in assisting the introduction of other medical devices. Their usage ranks first among biomedical materials and continues to rise. Medical catheters generally possess characteristics such as soft texture, chemical stability, low cost and availability, and good biocompatibility. They are typically made from polymers such as polyurethane (PU), silicone rubber (SR), and polyvinyl chloride (PVC). However, because polymers themselves lack antibacterial properties, bacteria can easily colonize their surfaces, forming biofilms that can lead to infections, affecting treatment outcomes and increasing the financial burden and physical suffering of patients. Therefore, developing and preparing catheter materials with antibacterial properties can not only improve treatment effectiveness but also reduce medical costs for patients to some extent.
[0003] Currently, antibacterial agents can be classified into three main categories based on their physicochemical properties: inorganic antibacterial agents, organic antibacterial agents, and natural antibacterial agents. Inorganic antibacterial agents, represented by silver, copper, and zinc, were the earliest type of antibacterial materials used. Although their antibacterial effects have been proven, their high cost, color, and potential harm to humans make them difficult to apply to human health. Organic antibacterial agents, including organic acids, phenols, quaternary ammonium salts, and benzimidazoles, are composed of organic compounds. These agents suffer from poor heat resistance, easy hydrolysis, and short shelf life, and their safety remains to be investigated. In contrast, antimicrobial peptides derived from insects and plants, as representatives of natural antibacterial agents, possess thermal stability, broad-spectrum antibacterial activity, and biocompatibility. They can largely solve the problems of high cost, poor stability, easy hydrolysis, and short shelf life associated with the aforementioned two types of antibacterial agents. Furthermore, because they originate from living organisms, they avoid the problem of drug resistance that can develop during use. Therefore, their application in the field of antibacterial medical materials is of great significance for improving biomedical safety.
[0004] In traditional research, inorganic nanoparticles have been widely used as drug carriers in clinical treatment. Mesoporous materials, in particular, are widely applied in numerous fields due to their regular pore structure, tunable pore size, high specific surface area, and ease of surface modification. Mesoporous silica, with its advantages of being non-toxic, odorless, pollution-free, having controllable particle size, being easily phagocytosed by cells, exhibiting good biocompatibility, and being non-cytotoxic, is widely used in biotherapy and drug delivery. The Steffen Stenger team synthesized dendritic mesoporous silica nanoparticles loaded with aspartic protease-derived peptides for the inactivation of intracellular mycobacteria (Adv. HealthcareMater. 2021, 10, 2100453). The mesoporous dendritic silica not only increases the loading capacity of the aspartic protease-derived peptides but also enables controlled release. Elisa Parra-Ortiz's team prepared virus-like mesoporous silica as a carrier for the antimicrobial peptide LL-37. They compared its biological behavior with that of smooth and non-porous mesoporous silica, demonstrating that the virus-like surface structure can increase the loading of LL-37 while simultaneously disrupting cell membranes. This provides a promising approach for designing nanoparticles as carriers for antimicrobial peptide delivery (ACSnano, 2021, 5, 4, 6787-6800). Chen et al. reported a Cu-ion-coordinated antimicrobial peptide / mussel adhesion protein grafted onto an implanted catheter, endowing the catheter with excellent stability, antimicrobial properties, and biocompatibility. In summary, the results indicate that mesoporous silica-loaded antimicrobial peptides can exert excellent effects in drug delivery and release. Furthermore, the antimicrobial peptides exhibit good antimicrobial effects as broad-spectrum antimicrobial agents. However, mesoporous silica-loaded peptides typically function in particle form, and there are currently no reports on the application of silica-antimicrobial peptides modified on catheter materials in the fields of medical antimicrobial and anti-adhesion. Summary of the Invention
[0005] The purpose of this invention is to provide an antibacterial and anti-adhesion medical catheter with excellent biocompatibility and its preparation method. Catheters, as the most widely used medical material, are extensively applied in clinical and adjuvant therapies. Mesoporous silica and antimicrobial peptides are both biocompatible substances and have been proven to be safe for use in vivo. Modifying the surface of commercial catheters with mesoporous silica loaded with antimicrobial peptides imparts excellent antibacterial and anti-adhesion properties to the catheter material without affecting its biocompatibility. The prepared mesoporous silica-loaded antimicrobial peptide-modified catheter material exhibits good scalability, stability, biocompatibility, antibacterial properties, and anti-adhesion, which can significantly reduce bacterial infection problems during catheter use and is highly suitable for related applications in the biomedical antimicrobial field.
[0006] The present invention discloses a method for preparing a biocompatible, antibacterial, and anti-adhesion medical catheter, the steps of which are as follows:
[0007] 1) Dissolve 0.8–1.0 mL of 0.1 M sodium hydroxide (NaOH) aqueous solution and 0.8–1.2 g of hexadecyltrimethylammonium bromide (CTAB) in 40–80 mL of deionized water, and stir at 50–70 °C for 2–4 h to obtain CTAB template solution;
[0008] 2) Add 18-24 mL of a 20% (v / v) tetraethyl orthosilicate (TEOS) cyclohexane solution to the CTAB template solution obtained in step 1), and stir continuously at 50-70 °C for 48-72 h to obtain a spiky mesoporous silica (SiO2) dispersion; then add 5-10 mL of a 1 mg / mL antimicrobial peptide (AMPs) solution, and continue stirring for 12-24 h to allow the silica and antimicrobial peptides to react fully, and then reflux in acetone to remove the CTAB template;
[0009] 3) The product after reflux in step 2) is centrifuged and washed 3 to 5 times with ethanol and water respectively, and the supernatant is removed to obtain a composite nanoparticle precipitate of spiny mesoporous silica (SiO2) loaded with antimicrobial peptides.
[0010] 4) The composite nanoparticles obtained in step 3) are precipitated and dried under vacuum to obtain SiO2@AMPs composite nanoparticles;
[0011] 5) Place the commercial medical catheter in medical alcohol and ultrasonically clean it 3-5 times to remove surface impurities, then dry it to obtain a clean medical catheter for subsequent modification.
[0012] 6) Prepare an adhesive solution with a mass fraction of 8-15% and a SiO2@AMPs solution of 40-60 μg / mL. First, spray the adhesive solution onto the clean medical catheter surface obtained in step 5), and then spray the SiO2@AMPsD PBS solution onto the medical catheter surface to load it onto the catheter surface.
[0013] 7) Place the modified medical catheter from step 6) in an oven and dry it at 50-70°C for 2-6 hours to obtain the antibacterial and anti-adhesion medical catheter with excellent biocompatibility as described in this invention.
[0014] The antimicrobial peptide solution mentioned in step 2) is a PBS buffer solution of antimicrobial peptides;
[0015] The centrifugal cleaning process described in step 3) is performed at a speed of 8000–12000 r / min for 8–12 min.
[0016] The vacuum drying temperature in step 4) is 35–45°C, and the time is 24–72 hours.
[0017] Step 5) Commercially available medical catheters are one of the following: polyurethane catheters, polytetrafluoroethylene catheters, polymethyl methacrylate catheters, polydimethylsiloxane catheters, and polyvinyl chloride catheters; the catheter diameter is 3–10 mm. The drying temperature is 50–70°C.
[0018] The adhesive mentioned in step 6) is one of polydimethylsiloxane (PDMS), polyvinylidene fluoride (PVDF), and polytetrafluoroethylene (PTFE), and the solvent is one of n-hexane, cyclohexane, and dichloromethane; the volume of adhesive solution sprayed per centimeter of the conduit surface in the subsequent treatment is 0.5 to 2 mL, and the volume of SiO2@AMPs solution sprayed is 1 to 5 mL.
[0019] This invention uses commercial medical catheters as raw materials and modifies them with AMPs-loaded SiO2 nanoparticles (SiO2@AMPs) to obtain an antibacterial and anti-adhesion catheter material with good biocompatibility. This invention has advantages such as low cost, good reproducibility, and mass production capability. The medical catheters prepared by this invention exhibit excellent surface antibacterial and antibacterial adhesion properties, as well as excellent anti-protein adsorption capacity. The bactericidal efficiency and anti-adhesion efficiency against *Escherichia coli* and *Staphylococcus aureus* on the material surface can both reach over 99%; in simulated in vivo antibacterial systems, the bactericidal efficiency against *Escherichia coli* and *Staphylococcus aureus* prepared by this invention can both reach over 99.99%, and the protein adhesion efficiency of the material is less than 6%. Furthermore, the SiO2@AMPs-modified catheters prepared by this invention exhibit good biocompatibility. Currently, there are no reports on the use of SiO2-loaded antimicrobial peptide materials for antibacterial modification of medical catheters. This antibacterial and anti-adhesion medical catheter, which has excellent biocompatibility, is easy to prepare, has good stability and scalability, and shows broad application prospects in the fields of biomedicine and antibacterial. Attached Figure Description
[0020] Figure 1 (1): A scanning electron microscope image of the surface of an unmodified commercial medical PVC catheter; Figure 1 (2): A scanning electron microscope image of the surface of the antibacterial and anti-adhesion catheter prepared in Example 1;
[0021] Figure 2 Infrared spectra of the spiny SiO2 prepared in Example 1, the antimicrobial peptides AMPs used in Example 1, and the antimicrobial peptide-modified SiO2 (SiO2@AMPs) composite nanoparticles;
[0022] Figure 3 Image of antibacterial plating on catheter material surface: Figure 3 (1) and Figure 3(3) Antimicrobial images of commercially available, unmodified medical PVC catheters purchased directly. Figure 3 (2) and Figure 3 (4) An antibacterial image of the antibacterial and anti-adhesion medical catheter prepared in Example 1; Figure 3 (1) and Figure 3 (2) The bacteria used is Escherichia coli. Figure 3 (3) and Figure 3 (4) The bacteria used is Staphylococcus aureus;
[0023] Figure 4 Image of antibacterial plate coating of catheter material solution system: Figure 4 (1) and Figure 4 (3) Antimicrobial images of commercially available, unmodified medical PVC catheters purchased directly. Figure 4 (2) and Figure 4 (4) An antibacterial image of the antibacterial and anti-adhesion medical catheter prepared in Example 1; Figure 4 (1) and Figure 4 (2) The bacteria used is Escherichia coli. Figure 4 (3) and Figure 4 (4) The bacteria used is Staphylococcus aureus;
[0024] Figure 5 Images showing the antibacterial adhesion properties of the antibacterial and anti-adhesion catheter prepared in Example 1 and the surface of a commercial medical PVC catheter. Figure 5 (1) and Figure 5 (3) Antimicrobial images of commercially available, unmodified medical PVC catheters purchased directly. Figure 5 (2) and Figure 5 (4) An antibacterial image of the antibacterial and anti-adhesion medical catheter prepared in Example 1; Figure 5 (1) and Figure 5 (2) The bacteria used is Escherichia coli. Figure 5 (3) and Figure 5 (4) The bacteria used is Staphylococcus aureus;
[0025] Figure 6 Microscopic images of cell growth in duct materials using the contact and co-culture methods: Figure 6 (1) (directly purchased unmodified commercial medical PVC catheters) and Figure 6 (2) (The antibacterial and anti-adhesion medical catheter prepared in Example 1) is a cell growth microscope image obtained by contact method; Figure 6 (3) (directly purchased unmodified commercial medical PVC catheters) and Figure 6 (4) (Antibacterial and anti-adhesion medical catheter prepared in Example 1) is a microscopic image of cell growth by co-culture method;
[0026] Figure 7 : Bar graph of protein adsorption efficiency of commercial medical PVC catheters and antibacterial and anti-adhesion medical catheters prepared in Example 1. The protein used in the test was newborn bovine serum albumin.
[0027] like Figure 1 As shown in the figure, the prepared SiO2@AMPs composite nanoparticles are very uniformly modified on the surface of the conduit.
[0028] like Figure 2 As shown, the infrared spectral characteristic peaks of the SiO2@AMPs composite nanoparticles prepared in Example 1 correspond to the characteristic peaks of SiO2 and AMPs, respectively, proving that AMPs were successfully loaded onto SiO2.
[0029] like Figure 3 As shown, the surface antibacterial properties (surface antibacterial properties refer to the antibacterial activity of the antibacterial and anti-adhesion medical catheter prepared in Example 1 and the commercial medical PVC catheter, respectively) were compared using the plate count method. The antibacterial and anti-adhesion catheter prepared in Example 1 showed a 99.96% bactericidal efficiency against Escherichia coli and a greater than 99.99% bactericidal efficiency against Staphylococcus aureus, while the bactericidal efficiency of the commercial medical PVC catheter was less than 20%.
[0030] like Figure 4 As shown, the antibacterial and anti-adhesion catheter prepared in Example 1 and the antibacterial properties of commercial medical PVC catheter solutions (solution antibacterial refers to the process of placing the catheter material in a bacterial solution, culturing them together at 37°C for 2 hours, and then taking a certain amount of bacterial solution from the system for plate coating) were calculated by plate counting method. Compared with the blank control, the antibacterial and anti-adhesion catheter prepared in Example 1 had a bactericidal efficiency of more than 99.99% against Escherichia coli and Staphylococcus aureus, while the bactericidal efficiency of commercial medical PVC catheters was less than 20%.
[0031] like Figure 5 As shown, the antibacterial adhesion properties of the antibacterial and anti-adhesion catheters prepared in Example 1 and commercial medical PVC catheters were calculated using the plate count method. Compared with the blank control, the antibacterial medical catheters prepared in Example 1 showed anti-adhesion efficiencies of greater than 99.99% against Escherichia coli and Staphylococcus aureus. In contrast, the anti-adhesion efficiencies of commercial medical PVC catheters were all below 25%.
[0032] like Figure 6As shown, the biocompatibility tests of the antibacterial and anti-adhesion catheter prepared in Example 1 and the commercial medical polyvinyl chloride catheter, using both the contact method and the co-culture method, indicate that the catheter material did not adversely affect cell growth, demonstrating that the antibacterial and anti-adhesion catheter prepared in Example 1 and the commercial medical polyvinyl chloride catheter have good biocompatibility.
[0033] like Figure 7 As shown, the protein adsorption efficiency of the antibacterial and anti-adhesion catheter prepared in Example 1 and the commercial medical PVC catheter were used to evaluate the anti-protein adhesion performance of the materials. The results showed that the protein adsorption efficiency of the antibacterial and anti-adhesion catheter prepared in Example 1 was lower than that of the commercial medical PVC catheter, indicating that SiO2@AMPs composite nanoparticle modification can improve the anti-protein adhesion performance of the commercial medical PVC catheter to a certain extent. Detailed Implementation
[0034] The technical solution of the present invention will be described in more detail below with specific implementation examples, but the examples do not constitute a limitation of the present invention.
[0035] Example 1
[0036] 1) Dissolve 0.8 mL of 0.1 M sodium hydroxide (NaOH) aqueous solution and 1.0 g of cetyltrimethylammonium bromide (CTAB) in 50 mL of deionized water and stir at 60 °C for 4 h to obtain CTAB template solution;
[0037] 2) Take 20 mL of cyclohexane solution of tetraethyl orthosilicate (TEOS) with a volume fraction of 20% and add it to the CTAB template solution obtained in step 1). Stir continuously at 60 °C for 48 h to obtain a spiky mesoporous silica (SiO2) dispersion. Then add antimicrobial peptide (AMPs) solution (5 mL, 1 mg / mL, PBS buffer as solvent) and continue stirring for 24 h to allow the silica and antimicrobial peptides to react fully. Then reflux in acetone for 24 h to remove the CTAB template.
[0038] 3) The product after reflux in step 2) was washed three times by centrifugation with ethanol and water respectively, and the supernatant was removed to obtain a precipitate of spiny mesoporous silica (SiO2) loaded with antimicrobial peptide composite nanoparticles.
[0039] 4) The composite nanoparticles obtained in step 3) were precipitated and vacuum dried at 40°C for 40 h to obtain SiO2@AMPs composite nanoparticles;
[0040] 5) Place the purchased commercial medical PVC catheter (4.7 mm in diameter) in medical alcohol and ultrasonically clean it 3 times to remove impurities, then dry it at 60°C to obtain a clean medical catheter.
[0041] 6) Prepare a cyclohexane solution of 10% PDMS and a PBS solution of 50 μg / mL SiO2@AMPs. Cut the catheter obtained in step 5) into a 5 cm long segment. Then, spray 10 mL of PDMS solution evenly on the surface of the catheter and then spray 10 mL of SiO2@AMPs solution evenly on the surface of the catheter to load it on the surface of the catheter.
[0042] 7) Place the modified catheter from step 6) in an oven and dry it at 60°C for 4 hours to obtain an antibacterial and anti-adhesion medical catheter with excellent biocompatibility.
[0043] Example 1 Performance Test
[0044] Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli in their logarithmic growth phase were used for bactericidal and antibacterial adhesion experiments. 1. Evaluation of antibacterial properties on the catheter surface: 200 μL of bacterial solution was dropped onto the catheter surface and allowed to stand at room temperature for 2 hours. Then, it was transferred to 10 mL of PBS buffer, vortexed, and 200 μL of the bacterial solution was plated. The solution was then incubated at 37°C for 16 hours to evaluate the antibacterial properties of the catheter surface. 2. Evaluation of antibacterial properties of the catheter solution system: The catheter material was placed in 10 mL of bacterial solution in its logarithmic growth phase and incubated at 37°C for 2 hours. 200 μL of the bacterial solution was then plated and incubated at 37°C for 16 hours to evaluate the antibacterial properties of the catheter solution system. 3. Evaluation of antibacterial adhesion performance: The catheter and the bacterial solution cultured to the logarithmic growth phase were placed together at 37°C for 4 hours. The catheter was then removed from the bacterial solution and transferred to 10 mL of PBS. The bacteria adhering to the catheter were collected by vortexing. 200 μL of bacterial solution was then taken from the bacterial PBS dispersion, plated, and incubated at 37°C for 16 hours to evaluate the antibacterial adhesion performance of the catheter material.
[0045] Mouse fibroblasts (NIH / 3T3) were used as an indicator to evaluate the biocompatibility of the materials. 1. Biocompatibility was evaluated using the contact method: First, the cells were cultured in a constant temperature incubator for 6 hours until they adhered and grew. Then, the conduit material was placed in cell culture medium and cultured for another 12 hours. Cell growth was observed using an inverted fluorescence microscope. 2. Biocompatibility was evaluated using the co-culture method: The revived cells and conduit material were placed together in cell culture medium and co-cultured for 18 hours. Cell growth was observed using an inverted fluorescence microscope.
[0046] Finally, the protein adsorption capacity of the catheter material was detected using the BCA protein assay reagent. The protein used in the test was newborn bovine serum albumin, and the concentration of residual protein was detected using an enzyme-linked immunosorbent assay (ELISA) reader.
[0047] Example 2
[0048] 1) Dissolve 1.0 mL of 0.1 M sodium hydroxide (NaOH) aqueous solution and 1.2 g of hexadecyltrimethylammonium bromide (CTAB) in 50 mL of deionized water and stir at 60 °C for 4 h to obtain CTAB template solution;
[0049] 2) Take 20 mL of cyclohexane solution of tetraethyl orthosilicate (TEOS) with a volume fraction of 20% and add it to the CTAB template solution obtained in step 1). Stir continuously at 60 °C for 48 h to obtain a spiky mesoporous silica (SiO2) dispersion. Then add antimicrobial peptide (AMPs) solution (5 mL, 1 mg / mL, PBS buffer as solvent) and continue stirring for 24 h to allow the silica and antimicrobial peptides to react fully. Then reflux in acetone for 24 h to remove the CTAB template.
[0050] 3) The refluxed product was centrifuged and washed three times with ethanol and water respectively, and the supernatant was removed to obtain a precipitate of spiny mesoporous silica (SiO2) loaded with antimicrobial peptide composite nanoparticles.
[0051] 4) The precipitate obtained in step 3) was vacuum dried at 40℃ for 40h to obtain SiO2@AMPs composite nanoparticles;
[0052] 5) Place the purchased commercial medical PVC catheter (4.7mm in diameter) in medical alcohol and ultrasonically clean it 3 times to remove impurities. Dry it at 60℃ and then proceed with subsequent processing.
[0053] 6) Prepare a cyclohexane solution of 10% PDMS and a PBS solution of 50 μg / mL SiO2@AMPs. Cut the catheter obtained in step 5) into a 5 cm long segment. Then, spray 10 mL of PDMS solution evenly on the surface of the catheter and then spray 10 mL of SiO2@AMPs solution evenly on the surface of the catheter to load it on the surface of the catheter.
[0054] 7) Place the modified catheter in an oven and dry it at 60°C for 4 hours to obtain an antibacterial and anti-adhesion medical catheter with excellent biocompatibility.
[0055] The antibacterial medical catheter prepared in Example 2 has an antibacterial rate of over 99% on both the surface and in the solution system, and exhibits good biocompatibility.
[0056] Example 3
[0057] 1) Dissolve 0.8 mL of 0.1 M sodium hydroxide (NaOH) aqueous solution and 1.0 g of cetyltrimethylammonium bromide (CTAB) in 50 mL of deionized water and stir at 60 °C for 4 h to obtain CTAB template solution;
[0058] 2) Take 22 mL of cyclohexane solution of tetraethyl orthosilicate (TEOS) with a volume fraction of 20% and add it to the CTAB template solution obtained in step 1). Stir continuously at 60 °C for 48 h to obtain a spiky mesoporous silica (SiO2) dispersion. Then add antimicrobial peptide (AMPs) solution (5 mL, 1 mg / mL, PBS buffer as solvent) and continue stirring for 24 h to allow the silica and antimicrobial peptides to react fully. Next, reflux in acetone for 24 h to remove the CTAB template.
[0059] 3) The refluxed product was centrifuged and washed three times with ethanol and water respectively, and the supernatant was removed to obtain a precipitate of spiny mesoporous silica (SiO2) loaded with antimicrobial peptide composite nanoparticles.
[0060] 4) The precipitate obtained in step 3) was vacuum dried at 40℃ for 40h to obtain SiO2@AMPs composite nanoparticles;
[0061] 5) Place the purchased commercial medical PVC catheter (4.7mm in diameter) in medical alcohol and ultrasonically clean it 3 times to remove impurities. Dry it at 60℃ and then proceed with subsequent processing.
[0062] 6) Prepare a cyclohexane solution of 10% PDMS and a PBS solution of 50 μg / mL SiO2@AMPs. Cut the catheter obtained in step 5) into a 5 cm long segment. Then, spray 10 mL of PDMS solution evenly on the surface of the catheter and then spray 10 mL of SiO2@AMPs solution evenly on the surface of the catheter to load it on the surface of the catheter.
[0063] 7) Place the modified catheter in an oven and dry it at 60°C for 4 hours to obtain an antibacterial and anti-adhesion medical catheter with excellent biocompatibility.
[0064] The antibacterial medical catheter prepared in Example 3 has an antibacterial rate of over 99% on both the surface and in the solution system, and exhibits good biocompatibility.
[0065] Example 4
[0066] 1) Dissolve 1.0 mL of 0.1 M sodium hydroxide (NaOH) aqueous solution and 1.2 g of hexadecyltrimethylammonium bromide (CTAB) in 50 mL of deionized water and stir at 60 °C for 4 h to obtain CTAB template solution;
[0067] 2) Add 24 mL of a 20% (v / v) tetraethyl orthosilicate (TEOS) cyclohexane solution to the CTAB template solution obtained in step 1), and stir continuously at 60 °C for 48 h to obtain a spiky mesoporous silica (SiO2) dispersion. Then add an antimicrobial peptide (AMP) solution (5 mL, 1 mg / mL, PBS buffer), and continue stirring for 24 h to allow the silica and antimicrobial peptides to react fully. Next, reflux in acetone for 24 h to remove the CTAB template.
[0068] 3) The refluxed product was centrifuged and washed three times with ethanol and water respectively, and the supernatant was removed to obtain a precipitate of spiny mesoporous silica (SiO2) loaded with antimicrobial peptide composite nanoparticles.
[0069] 4) The precipitate obtained in step 3) was vacuum dried at 40℃ for 40h to obtain SiO2@AMPs composite nanoparticles;
[0070] 5) Place the purchased commercial medical PVC catheter (4.7mm in diameter) in medical alcohol and ultrasonically clean it 3 times to remove impurities. Dry it at 60℃ and then proceed with subsequent processing.
[0071] 6) Prepare a cyclohexane solution of 10% PDMS and a PBS solution of 50 μg / mL SiO2@AMPs. Cut the catheter obtained in step 5) into a 5 cm long segment. Then, spray 10 mL of PDMS solution evenly on the surface of the catheter and then spray 10 mL of SiO2@AMPs solution evenly on the surface of the catheter to load it on the surface of the catheter.
[0072] 7) Place the modified catheter in an oven and dry it at 60°C for 4 hours to obtain an antibacterial and anti-adhesion medical catheter with excellent biocompatibility.
[0073] The antibacterial medical catheters prepared in Example 4 exhibited antibacterial rates exceeding 99% on both the surface and in the solution system, and also demonstrated good biocompatibility.
[0074] Example 5
[0075] 1) Dissolve 0.8 mL of 0.1 M sodium hydroxide (NaOH) aqueous solution and 1.0 g of cetyltrimethylammonium bromide (CTAB) in 50 mL of deionized water and stir at 60 °C for 4 h to obtain CTAB template solution;
[0076] 2) Take 20 mL of cyclohexane solution of tetraethyl orthosilicate (TEOS) with a volume fraction of 20% and add it to the CTAB template solution obtained in step 1). Stir continuously at 60 °C for 48 h to obtain a spiky mesoporous silica (SiO2) dispersion. Then add antimicrobial peptide (AMPs) solution (5 mL, 1 mg / mL, PBS buffer as solvent) and continue stirring for 24 h to allow the silica and antimicrobial peptides to react fully. Next, reflux in acetone for 24 h to remove the CTAB template.
[0077] 3) The refluxed product was centrifuged and washed three times with ethanol and water respectively, and the supernatant was removed to obtain a precipitate of spiny mesoporous silica (SiO2) loaded with antimicrobial peptide composite nanoparticles.
[0078] 4) The precipitate obtained in step 3) was vacuum dried at 40℃ for 40h to obtain SiO2@AMPs composite nanoparticles;
[0079] 5) Mix the purchased polydimethylsiloxane (PDMS, Dow Corning 184) precursor and curing agent at a mass ratio of 10:1 and inject them into the template. Cure at 60°C for 2 hours to obtain PDMS conduit (diameter of 6mm). Place the PDMS conduit in medical alcohol and ultrasonically clean it 3 times to remove impurities. Dry it at 60°C and then carry out subsequent processing.
[0080] 6) Prepare a cyclohexane solution of 10% PDMS and a PBS solution of 50 μg / mL SiO2@AMPs. Cut the catheter obtained in step 5) into a 5 cm long segment. Then, spray 10 mL of PDMS solution evenly on the surface of the catheter and then spray 10 mL of SiO2@AMPs solution evenly on the surface of the catheter to load it on the surface of the catheter.
[0081] 7) Place the modified catheter in an oven and dry it at 60°C for 4 hours to obtain an antibacterial and anti-adhesion medical catheter with excellent biocompatibility.
[0082] The antibacterial medical catheter prepared in Example 5 has an antibacterial activity of over 99% on both the surface and in the solution system, and exhibits good biocompatibility.
Claims
1. A method for preparing a biocompatible, antibacterial, and anti-adhesion medical catheter, comprising the following steps: 1) Dissolve 0.8~1.0 mL of 0.1 M sodium hydroxide aqueous solution and 0.8~1.2 g of hexadecyltrimethylammonium bromide in 40~80 mL of water, and stir at 50~70℃ for 2~4 h to obtain CTAB template solution; 2) Add 18-24 mL of a 20% tetraethyl orthosilicate cyclohexane solution to the CTAB template solution obtained in step 1), and stir continuously at 50-70°C for 48-72 h to obtain a spiky mesoporous silica dispersion; then add 5-10 mL of a 1 mg / mL PBS buffer solution of antimicrobial peptide, and continue stirring for 12-24 h to allow the silica and antimicrobial peptide to react fully, and then reflux in acetone to remove the CTAB template; 3) The product after reflux in step 2) is centrifuged and washed 3-5 times with ethanol and water respectively, and the supernatant is removed to obtain a composite nanoparticle precipitate of spiny mesoporous silica loaded with antimicrobial peptides. 4) The composite nanoparticles obtained in step 3) are precipitated and vacuum dried to obtain SiO2@AMPs composite nanoparticles; the vacuum drying temperature is 35~45℃ and the time is 24~72h. 5) Place the medical catheter in medical alcohol and ultrasonically clean it 3-5 times to remove surface impurities, then dry it to obtain a clean medical catheter; the medical catheter is one of polyurethane catheter, polytetrafluoroethylene catheter, polymethyl methacrylate catheter, polydimethylsiloxane catheter, and polyvinyl chloride catheter, with a catheter diameter of 3-10 mm, and the drying temperature is 50-70℃. 6) Prepare an adhesive solution with a mass fraction of 8-15% and a SiO2@AMPs solution with a mass fraction of 40-60 μg / mL. First, spray the adhesive solution onto the clean medical catheter surface obtained in step 5), and then spray the SiO2@AMPs solution onto the medical catheter surface to load it onto the catheter surface. The adhesive is one of polydimethylsiloxane, polyvinylidene fluoride, and polytetrafluoroethylene, and the solvent is one of n-hexane, cyclohexane, and dichloromethane. The volume of adhesive solution sprayed per centimeter of catheter surface is 0.5-2 mL, and the volume of SiO2@AMPs solution sprayed is 1-5 mL. 7) Place the modified medical catheter from step 6) in an oven and dry it at 50-70°C for 2-6 hours to obtain the biocompatible antibacterial and anti-adhesion medical catheter.
2. The method for preparing a biocompatible antibacterial and anti-adhesion medical catheter as described in claim 1, characterized in that: Step 3) The centrifugal cleaning speed is 8000~12000 r / min, and the time is 8~12 min.
3. A biocompatible, antibacterial, and anti-adhesion medical catheter, characterized in that: It is prepared by the method described in any one of claims 1 or 2.
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