Antibacterial coating material, preparation method of antibacterial coating material, surgical suture and preparation method of surgical suture

Abstract

The invention discloses an antibacterial coating material and a preparation method thereof as well as a surgical suture and a preparation method thereof, and belongs to the field of medical materials. The preparation method comprises the following steps: grafting a quaternary ammonium salt group and a catechol group to chitosan, modifying the chitosan, and reacting the modified chitosan with silver nitrate to generate nano-silver. Modified chitosan is adopted as a reducing agent and a stabilizing agent, a stable nano-silver solution is formed under irradiation of light containing ultraviolet rays, the surface of an existing mainstream surgical suture main body is coated with a chitosan nano-silver composite material, and the surgical suture with the good antibacterial effect is obtained. According to the antibacterial coating material and the preparation method thereof as well as the surgical suture and the preparation method thereof, the antibacterial effect can be improved, the preparation method is simple, the process condition is mild, and the antibacterial coating material is suitable for large-scale production.

Description

Technical Field

[0001] The invention relates to medical materials, in particular to an antibacterial coating material and a preparation method thereof, and a surgical suture and a preparation method thereof. Background Art

[0002] Surgical sutures are key materials used to connect and fix tissues during surgery. How to give sutures antibacterial properties has become one of the key research directions. Surgical sutures come into contact with wounds and body fluids, which can easily become a breeding ground for bacteria, increasing the risk of postoperative infection. Current solutions include adding antibacterial ingredients to suture materials or coating their surfaces with antibacterial layers.

[0003] Chitosan is a natural polysaccharide polymer with good biocompatibility and biodegradability, and therefore has attracted much attention in medical materials. However, its antibacterial effect may be weakened by changes in environmental pH, and its stability in combination with other materials needs to be improved.

[0004] Nanosilver is an important antibacterial material. Its advantage lies in its broad-spectrum antibacterial property, which can effectively fight against a variety of bacteria, fungi and other pathogens. However, the rate of silver ion release is difficult to control and may induce cytotoxic reactions. Summary of the invention

[0005] Purpose of the invention: The purpose of the present invention is to provide an antibacterial coating material that improves antibacterial effect, reduces energy consumption and saves costs.

[0006] Another object of the present invention is to provide a method for preparing an antibacterial coating material that has improved antibacterial effect, is simple in preparation, has mild process conditions, and is suitable for large-scale production.

[0007] Another object of the present invention is to provide a surgical suture with good antibacterial effect, short soaking time and fast drying speed.

[0008] Another object of the present invention is to provide a method for preparing surgical sutures that has improved antibacterial effect and is suitable for large-scale production.

[0009] Technical solution: The antibacterial coating material of the present invention comprises quaternary ammonium salt-catechol modified chitosan and nano-silver. The nano-silver particles are coated with quaternary ammonium salt-catechol modified chitosan, and the quaternary ammonium salt-catechol modified chitosan comprises 5-20% quaternization and 10-30% catecholization.

[0010] Preferably, the nano silver is generated by a one-step rapid reaction of quaternary ammonium salt-catechol modified chitosan as a reducing agent and a stabilizer with silver nitrate under light.

[0011] The method for preparing an antibacterial coating material according to the present invention comprises the following steps:

[0012] (1) preparing quaternary ammonium salt modified chitosan;

[0013] (2) preparing quaternary ammonium salt-catechol modified chitosan;

[0014] (3) Preparation of nanosilver and antibacterial coating materials.

[0015] Preferably, the step (1) comprises: dissolving chitosan in an acetic acid solution, adding (3-chloro-2-hydroxypropyl)trimethylammonium chloride dropwise under stirring in a water bath; taking out after stirring in a constant temperature water bath, fully cooling, filtering, dialyzing, and freeze-drying.

[0016] The step (2) comprises: dissolving the quaternary ammonium salt modified chitosan obtained in the step (1) in water, adding 3,4-dihydroxybenzaldehyde solution, stirring at room temperature; suction filtering, dialysis, and freeze drying.

[0017] The step (3) comprises: dissolving the quaternary ammonium salt-catechol modified chitosan obtained in the step (2) in ultrapure water, adding silver nitrate solution to obtain nano silver; fully stirring and mixing, and irradiating with light.

[0018] Preferably, in the step (1), the molecular weight of chitosan is 100,000-300,000 g / mol, and the degree of deacetylation is 80-95%.

[0019] Preferably, in the step (1), the mass concentration of the acetic acid solution is 0.3-4wt%; the mass concentration of (3-chloro-2-hydroxypropyl)trimethylammonium chloride is 50-70wt%; the concentration of chitosan in the control system is 0.1-2wt%, and the concentration of (3-chloro-2-hydroxypropyl)trimethylammonium chloride is 1.5-2wt%; the reaction temperature is 60-80°C; and the reaction time is 8-12h.

[0020] Preferably, in the step (2), the quaternary ammonium salt-modified chitosan is dissolved in water to form a solution with a concentration of 0.005-0.015 g / mL; the concentration of the 3,4-dihydroxybenzaldehyde solution is 0.03-0.08 g / mL; the stirring time is 2-5 h; and the dialysate is an acetic acid solution with a pH of 4-4.5.

[0021] Preferably, in the step (3), the quaternary ammonium salt-catechol modified chitosan is dissolved in ultrapure water to obtain a solution concentration of 1-2wt%; the concentration of the silver nitrate solution is 0.01-0.02mol / L; the volume ratio of the quaternary ammonium salt-catechol modified chitosan solution to the silver nitrate solution is 10:1; the light is light containing ultraviolet rays, preferably natural light or lamplight; and the light irradiation time is 5-10min.

[0022] The method for preparing the surgical suture of the present invention comprises the following coating operations: immersing the surgical suture body in an antibacterial coating material, pulling out the surgical suture body at a constant speed, and drying at room temperature to obtain the surgical suture.

[0023] Preferably, in the coating operation, the main body of the surgical suture is one of polyglycolic acid (PGA), polydioxanone (PDO), catgut, silk, and nylon; the immersion time is 1-5 min; the constant speed is 1-10 cm / s; and the coating operation is repeated 1-4 times.

[0024] Principle of the invention:

[0025] As an antibacterial material, chitosan can release positively charged amino ions in an aqueous environment and bind to negatively charged bacterial cell membranes, thereby inhibiting bacterial proliferation. Therefore, combining chitosan with other antibacterial components and performing surface modification to enhance its antibacterial and adhesion properties is an effective way to realize its potential.

[0026] Catechol is a naturally occurring phenolic compound with strong adhesion ability. It can bind to the surface of a variety of substrates. This property makes catechol widely used in the surface modification of biomedical materials. By modifying chitosan with catechol, its surface adhesion can be significantly improved, ensuring that the antibacterial components are more firmly attached to the surface of surgical sutures. In addition, catechol itself also has certain antibacterial activity, and the synergistic effect with chitosan can further enhance the antibacterial effect of sutures. Based on this, modifying chitosan with catechol can not only improve the antibacterial properties, but also make the sutures work more persistently after surgery.

[0027] Nanosilver is an important antibacterial material. Its mechanism of action is mainly to release silver ions, interfere with the metabolic process of bacteria and the integrity of cell membranes, thereby achieving antibacterial effects. The advantage of nanosilver lies in its broad-spectrum antibacterial properties, which can effectively fight against a variety of bacteria, fungi and other pathogens. Compounding or coating nanosilver with other materials to slowly release silver ions and reduce toxicity risks is an important means to improve its safety and effectiveness.

[0028] The method uses modified chitosan as a reducing agent and stabilizer to react with silver nitrate in one step under light to generate a nanosilver solution. The modified chitosan molecules between the nanosilver particles can effectively prevent the nanosilver from agglomerating or precipitating. The antibacterial coating material synthesized by the method can be left to stand for a long time without coagulation. In addition, in the process of coating the suture body, the adhesion of the catechol group helps the coating material adhere to the surface of the suture body, is not easy to fall off, and forms a stable antibacterial surface layer.

[0029] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0030] (1) High antibacterial efficiency. The antibacterial rate of the surgical suture prepared by the method is as high as 96%.

[0031] (2) Short soaking time. The main body of the surgical suture in the present invention only needs to be soaked in the antibacterial coating material for 1-5 minutes, which is much shorter than the soaking time of several hours in the prior art. In addition, there is no need to use a strong acid solution such as ferric chloride to solidify the surface material, which effectively avoids damage to the physical properties of the surgical suture caused by strong acid.

[0032] (3) Fast drying speed. The method for preparing surgical sutures provided by the present invention does not require downtime to wait for drying, and does not require complex or expensive drying equipment. Drying can be completed at room temperature, greatly reducing energy consumption and equipment investment costs.

[0033] (4) Simple operation and few repetitions. The present invention only needs to repeat the coating operation 1-4 times to obtain surgical sutures with good antibacterial effect. The preparation process is simple, the process steps are reduced, and complex treatment or multiple treatment processes are avoided.

[0034] (5) Satisfy the needs of industrialized large-scale production. The suture of the present invention is pulled out of the solution and dried at a constant speed of 1-10 cm / s. The main body of the surgical suture begins to dry in the air after being pulled out of the solution. The continuity is extremely strong, and there is no interruption from immersion to drying. It is suitable for linear process production and highly automated assembly line operation.

[0035] (6) The process conditions are mild and suitable for multi-line operation. This method only requires room temperature operation, does not require extreme conditions such as high temperature and high pressure, and has low requirements for equipment and environment. DETAILED DESCRIPTION

[0036] The technical solution of the present invention is further described below in conjunction with embodiments.

[0037] Example 1

[0038] The antibacterial coating material of the present invention comprises quaternary ammonium salt-catechol modified chitosan and nano silver. The nano silver particles are coated with quaternary ammonium salt-catechol modified chitosan, the quaternary ammonium salt-catechol modified chitosan comprises 5-20% quaternization and 10-30% catecholization, and the nano silver is generated by one-step rapid reaction of quaternary ammonium salt-catechol modified chitosan as a reducing agent and a stabilizer with silver nitrate under light.

[0039] The method for preparing the antibacterial coating material of the present invention comprises the following steps:

[0040] (1) Preparation of quaternary ammonium salt modified chitosan:

[0041] 0.2 g chitosan (150000 g / mol, deacetylation degree 95%) was dissolved in 20 ml 0.5 wt % acetic acid solution, and 0.4 ml 65 wt % (3-chloro-2-hydroxypropyl) trimethylammonium chloride was added dropwise under stirring in a water bath at 80° C.; the mixture was stirred in a constant temperature water bath at 80° C. for 10 h, taken out, fully cooled, filtered, dialyzed, and freeze-dried to obtain solid quaternary ammonium salt modified chitosan.

[0042] (2) Preparation of quaternary ammonium salt-catechol modified chitosan:

[0043] Dissolve 0.2 g of solid quaternary ammonium salt-modified chitosan in 20 ml of water, add 3,4-dihydroxybenzaldehyde solution (0.7 g of 3,4-dihydroxybenzaldehyde dissolved in 20 ml of methanol), and stir at room temperature for 4 h; remove insoluble impurities in the solution by suction filtration;

[0044] The filtered solution was placed in a dialysis bag, and the dialysate was an acetic acid solution with a pH of 4-4.5. The dialysate was dialyzed at room temperature for 48 hours, and the dialysate was replaced every 4-6 hours; then ultrapure water was used for 6 hours, and the dialysate was replaced once in the middle;

[0045] The dialyzed solution is placed in a freeze dryer and freeze-dried to obtain solid quaternary ammonium salt-catechol modified chitosan.

[0046] (3) Preparation of nanosilver and antibacterial coating materials:

[0047] 0.2 g of solid quaternary ammonium salt-catechol modified chitosan is dissolved in ultrapure water to prepare a 2 wt% quaternary ammonium salt-catechol modified chitosan solution; 1 ml of 0.01 mol / L silver nitrate solution is added to the quaternary ammonium salt-catechol chitosan solution, and the mixture is stirred and mixed to obtain nanosilver; the mixed system is irradiated with natural light for 10 minutes to obtain a quaternary ammonium salt-catechol modified chitosan nanosilver solution, i.e., an antibacterial coating material.

[0048] The method for preparing the surgical suture of the present invention comprises the following coating operations:

[0049] The PGA surgical suture body was immersed in the quaternary ammonium salt-catechol chitosan nanosilver solution prepared above for 1 min, and then the suture was pulled out at a constant speed of 5 cm / s and dried at room temperature for 1 min to obtain the surgical suture.

[0050] Antimicrobial test:

[0051] According to the experimental protocol in AATCC TM100-2019, the prepared surgical sutures were cut into pieces and 100 mg was weighed and placed in a test tube. 100 μL of 3×10 5Add CFU / ml of E. coli liquid to the test tube and mix with the broken thread. Incubate at 37℃ for 1h, then add 10mL PBS and shake to dilute and mix. Dilute the above dilution in multiple ratios and apply it to the plate culture medium, incubate at 37℃ for 24h, observe the number of colonies, and record the antibacterial rate data.

[0052] Embodiment 2-4

[0053] The same parts as those in Example 1 will not be described in detail. The difference is that, in the method for preparing surgical sutures, the coating operation is repeated 2, 3, and 4 times respectively.

[0054] Example 5

[0055] The same parts between this embodiment and embodiment 1 will not be repeated here. The difference is that in the method for preparing surgical sutures, PDO sutures are used as the main body of the surgical sutures.

[0056] Embodiment 6-8

[0057] The same parts between this embodiment and embodiment 5 are not repeated here. The difference is that in the method for preparing surgical sutures, the coating operation is repeated 2, 3, and 4 times respectively.

[0058] The antibacterial rates and standard deviations of the antibacterial rates of the surgical sutures prepared in Examples 1-8 are shown in Table 1.

[0059] Table 1 Experimental conditions and experimental results of Examples 1-8

[0060]

[0061] The results showed that the surgical sutures prepared in Examples 1-8 all exhibited significant antibacterial properties. It can be clearly seen that the antibacterial rate did not increase significantly when coated 3 times or more, but was significantly higher than the antibacterial rate when coated 1 or 2 times. Therefore, it is believed that a stronger antibacterial property is exhibited when coated three times.

[0062] Comparative Example 1

[0063] The same parts as those in Example 1 are not repeated here, except that, in step (2), 0.2 g of quaternary ammonium salt-modified chitosan is dissolved in 12 ml of water, 3,4-dihydroxybenzaldehyde solution (0.7 g of 3,4-dihydroxybenzaldehyde is dissolved in 20 ml of methanol) is added, and the mixture is stirred at room temperature for 4 h.

[0064] A large amount of insoluble gel-like brown-yellow material was seen precipitating, and the supernatant was transparent.

[0065] The supernatant was removed by suction filtration and the precipitated gel was washed three times with ultrapure water.

[0066] The washed material was placed in a freeze dryer and freeze-dried to obtain a solid brown-yellow modified chitosan powder. The powder did not dissolve significantly in ultrapure water and 1% acetic acid solution and could not be used for subsequent nanosilver and suture coating preparation.

[0067] Comparative Example 2

[0068] The same parts as those in Example 1 are not described in detail here, except that the nitrate concentration in step (3) is changed to 0.05 mol / L.

[0069] This comparative example generates a brick red gel, and an antibacterial coating material cannot be obtained, so the comparative example is not suitable for coating the main body of the surgical suture.

[0070] Comparative Example 3

[0071] The same parts as those in Example 1 are not described in detail here. The difference is that in step (3), after sufficient stirring and mixing, the quaternary ammonium salt-catechol chitosan-silver nitrate mixed system is not irradiated with natural light.

[0072] It takes 24 hours after the mixture is evenly mixed to see obvious solution color change and nanosilver generation, at which time the generated nanosilver particle size and distribution width are both large. Therefore, using natural light to irradiate the quaternary ammonium salt-catechol chitosan-silver nitrate mixed system can promote the generation of nanosilver and quickly obtain nanosilver with a small and uniform particle size.

[0073] Comparative Example 4

[0074] The same parts as those in Example 7 are not described in detail here. The difference is that, in the method for preparing the surgical suture, the speed of pulling out the surgical suture body is 20 cm / s.

[0075] In this comparative example, the pulling speed of the surgical suture body during coating exceeded the maximum pulling speed of 10 cm / s in this method, resulting in obvious droplets hanging on the surgical suture body, which in turn led to uneven coating and prolonged drying time. Therefore, the pulling speed of the surgical suture body in this method cannot be too fast.

Claims

1. An antibacterial coating material, characterized in that: The invention comprises quaternary ammonium salt-catechol modified chitosan and nano silver. The nano silver particles are coated with quaternary ammonium salt-catechol modified chitosan. The quaternary ammonium salt-catechol modified chitosan comprises 5-20% quaternization and 10-30% catecholization.

2. The antibacterial coating material according to claim 1, characterized in that: The nano silver is generated by a one-step rapid reaction of quaternary ammonium salt-catechol modified chitosan as a reducing agent and a stabilizer with silver nitrate under light.

3. A method for preparing the antibacterial coating material according to claim 1, characterized in that: The following steps are involved: (1) preparing quaternary ammonium salt modified chitosan; (2) preparing quaternary ammonium salt-catechol modified chitosan; (3) Preparation of nanosilver and antibacterial coating materials.

4. The preparation method according to claim 3, characterized in that: The step (1) comprises: dissolving chitosan in an acetic acid solution, adding (3-chloro-2-hydroxypropyl)trimethylammonium chloride dropwise under stirring in a water bath; taking out after stirring in a constant temperature water bath, fully cooling, filtering, dialysis, and freeze-drying.

5. The preparation method according to claim 3, characterized in that: The step (2) comprises: dissolving the quaternary ammonium salt modified chitosan obtained in the step (1) in water, adding 3,4-dihydroxybenzaldehyde solution, stirring at room temperature; suction filtering, dialysis, and freeze drying.

6. The preparation method according to claim 3, characterized in that: The step (3) comprises: dissolving the quaternary ammonium salt-catechol modified chitosan obtained in the step (2) in ultrapure water, adding silver nitrate solution to obtain nano silver; fully stirring and mixing, and irradiating with light to obtain an antibacterial coating material.

7. The preparation method according to claim 6, characterized in that: In the step (3), the concentration of the silver nitrate solution is 0.01-0.02 mol / L; and the light is light containing ultraviolet rays.

8. A surgical suture, characterized in that: The surgical suture is made of the antibacterial coating material described in claim 1.

9. A method for preparing the surgical suture according to claim 8, characterized in that: The method comprises the following covering operations: immersing the surgical suture body in the antibacterial covering material, pulling out the surgical suture body at a constant speed, and drying the surgical suture body at room temperature to obtain the surgical suture.

10. The method for preparing surgical suture according to claim 9, characterized in that: The constant speed is 1-10 cm / s, and the coating operation is repeated 1-4 times.

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