A hernia patch with antibacterial effect and a method for preparing the same

Abstract

This invention relates to the field of medical materials technology, specifically to a hernia patch with antibacterial properties and its preparation method. The preparation method includes the following steps: dispersing modified polydopamine, schizopolysaccharide, and chitosan in water, mixing them evenly to obtain a mixed solution; uniformly coating the mixed solution onto a substrate to form an antibacterial layer, and drying to obtain the final product. The hernia patch prepared using the above method not only possesses excellent antibacterial and anti-adhesion properties but also good cell compatibility.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, specifically to a hernia patch with antibacterial properties and its preparation method. Background Technology

[0002] A hernia occurs when an organ or tissue moves out of its normal anatomical position and enters another area through a congenital or acquired weak point, defect, or opening. Hernias not only affect a patient's daily life but can also be life-threatening. For adult hernia patients, surgery is usually performed to implant a mesh at the site of the tissue defect. Clinically, there are high requirements for the cell compatibility, tensile strength, antibacterial effect, and anti-adhesion properties of hernia meshes.

[0003] Polypropylene (PP) meshes are the most commonly used hernia meshes in clinical practice due to their lightweight, flexibility, good conformability, and low cost. However, PP meshes also have significant drawbacks, including susceptibility to infection and adhesion to internal organs. Adhesion between the PP mesh and internal organs can lead to pain, a foreign body sensation, the formation of large fibrous cysts, intestinal obstruction, and other digestive problems. Therefore, the development of novel hernia meshes that combine anti-adhesion and antibacterial effects is urgently needed. Summary of the Invention

[0004] In order to overcome the shortcomings of the prior art, the primary objective of this invention is to provide a method for preparing a hernia patch with antibacterial properties, which is simple in steps and easy to operate.

[0005] Another objective of this invention is to provide a hernia patch with antibacterial properties, which has good cell compatibility and excellent antibacterial and anti-adhesion properties.

[0006] The objective of this invention is achieved through the following technical solution:

[0007] A method for preparing a hernia patch with antibacterial properties includes the following steps:

[0008] Modified polydopamine, schizopolysaccharide, and chitosan were dispersed in water and mixed thoroughly to obtain a mixed solution.

[0009] Steps The mixed solution is uniformly coated onto the substrate to form an antibacterial layer, which is then dried to obtain the final product.

[0010] Further, steps The mass ratio of the modified polydopamine, schizopolysaccharide, chitosan, and water is (5-10):(1-5):(10-20):(25-30); the average molecular weight of the schizopolysaccharide is 10-30 KD.

[0011] Furthermore, the modified polydopamine is prepared as follows:

[0012] a. Add pretreated diatomaceous earth to an aqueous ethanol solution, then add vinyltriethoxysilane to react. After the reaction is complete, purify to obtain modified diatomaceous earth.

[0013] b. Add the modified diatomaceous earth and dopamine from step a to water and stir until homogeneous to obtain a mixture; add sodium periodate to the mixture and continue stirring until purified to obtain the final product.

[0014] Further, in step a, the mass ratio of pretreated diatomaceous earth to vinyltriethoxysilane is 1:(0.1-0.2); the volume ratio of ethanol to water in the ethanol-water solution is 4:1; the reaction temperature is 50-55℃, and the reaction time is 4-5h.

[0015] Furthermore, the preparation process of the pretreated diatomaceous earth is as follows: add diatomaceous earth to a sodium hydroxide solution with a mass fraction of 8-10%, stir at 30-40℃ for 3-4 hours, filter and dry, and then calcine at 300-350℃ for 2-3 hours.

[0016] Further, in step b, the mass ratio of dopamine, modified diatomaceous earth, and sodium periodate is 1:(0.05-0.1):(0.8-1.2).

[0017] Furthermore, the stirring time described in step b is 30-60 minutes.

[0018] Further, steps The coating amount of the antibacterial layer described herein is 450-550 g / m². 2 .

[0019] Further, steps The substrate is a polypropylene substrate.

[0020] An antibacterial hernia patch is prepared using the above-described method for preparing an antibacterial hernia patch.

[0021] The present invention has the following advantages over the prior art:

[0022] 1. The hernia patch of the present invention incorporates raw materials such as schizopolysaccharide and modified polydopamine. The modified polydopamine is obtained by first modifying diatomaceous earth with vinyltriethoxysilane, and then utilizing the self-polymerization property of dopamine to form a polydopamine coating on the surface of the modified diatomaceous earth. Experimental results show that the combined use of schizopolysaccharide and modified polydopamine effectively enhances the antibacterial and anti-adhesion properties of the hernia patch. Furthermore, the modified polydopamine forms hydrogen bonds with chitosan, enhancing its stability and antibacterial properties.

[0023] 2. The hernia patch obtained by this invention has excellent cell compatibility and can meet the requirements for implantation safety. Detailed Implementation

[0024] The present invention will be further described in detail below with reference to embodiments, but the implementation of the present invention is not limited thereto. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in this technical field. Test methods in the following embodiments that do not specify specific experimental conditions are generally performed according to conventional experimental conditions or experimental conditions recommended by the manufacturer. Unless otherwise specified, the reagents and raw materials used in the present invention are commercially available.

[0025] (I) Implementation Examples

[0026] Example 1

[0027] A method for preparing a hernia patch with antibacterial properties, the specific preparation process of which is as follows:

[0028] According to the mass ratio of modified polydopamine, schizopolysaccharide, chitosan, and water of 7:3:15:28, the modified polydopamine, schizopolysaccharide (average molecular weight of 20KD), and chitosan were dispersed in water and mixed evenly to obtain a mixed solution.

[0029] Apply the antibacterial layer at a rate of 500g / m². 2 , the steps The mixed solution is uniformly coated onto a polypropylene substrate to form an antibacterial layer, which is then dried to obtain the final product.

[0030] The specific preparation method of the above-mentioned modified polydopamine is as follows:

[0031] a. Diatomaceous earth was added to a 9% sodium hydroxide solution and stirred at 35°C for 3.5 h. After filtration and drying, it was calcined at 320°C for 2.5 h to obtain pretreated diatomaceous earth. The pretreated diatomaceous earth was added to an ethanol-water solution (the volume ratio of ethanol to water in the ethanol-water solution was 4:1) at a mass ratio of 1:0.15, followed by the addition of vinyltriethoxysilane. The mixture was reacted at 52°C for 4.5 h. After the reaction was completed, it was filtered, washed, and dried to obtain modified diatomaceous earth.

[0032] b. According to the mass ratio of dopamine, modified diatomaceous earth, and sodium periodate 1:0.08:1, add the modified diatomaceous earth and dopamine from step a to water, stir evenly at room temperature to obtain a mixture; then add sodium periodate to the mixture and continue stirring for 40 minutes, filter and wash repeatedly with deionized water, and then put it into a 50℃ oven for 16 hours to obtain the final product.

[0033] An antibacterial hernia patch was prepared using the above-described method.

[0034] Example 2

[0035] A method for preparing a hernia patch with antibacterial properties, the specific preparation process of which is as follows:

[0036] According to the mass ratio of modified polydopamine, schizopolysaccharide, chitosan, and water of 5:1:10:25, the modified polydopamine, schizopolysaccharide (average molecular weight of 10KD), and chitosan were dispersed in water and mixed evenly to obtain a mixed solution.

[0037] According to the antibacterial layer coating amount of 450g / m² 2 , the steps The mixed solution is uniformly coated onto a polypropylene substrate to form an antibacterial layer, which is then dried to obtain the final product.

[0038] The specific preparation method of the above-mentioned modified polydopamine is as follows:

[0039] a. Diatomaceous earth was added to an 8% sodium hydroxide solution and stirred at 30°C for 4 hours. After filtration and drying, it was calcined at 300°C for 3 hours to obtain pretreated diatomaceous earth. The pretreated diatomaceous earth was added to an ethanol-water solution (the volume ratio of ethanol to water in the ethanol-water solution was 4:1) at a mass ratio of 1:0.1, followed by the addition of vinyltriethoxysilane. The mixture was reacted at 50°C for 5 hours. After the reaction was completed, it was filtered, washed, and dried to obtain modified diatomaceous earth.

[0040] b. According to the mass ratio of dopamine, modified diatomaceous earth, and sodium periodate of 1:0.05:0.8, add the modified diatomaceous earth and dopamine from step a to water, stir evenly at room temperature to obtain a mixture; then add sodium periodate to the mixture and continue stirring for 30 min, filter and wash repeatedly with deionized water, and then put it into a 50℃ oven to dry for 16 h to obtain pre-modified polydopamine;

[0041] An antibacterial hernia patch was prepared using the above-described method.

[0042] Example 3

[0043] A method for preparing a hernia patch with antibacterial properties, the specific preparation process of which is as follows:

[0044] According to the mass ratio of modified polydopamine, schizopolysaccharide, chitosan, and water of 10:5:20:30, the modified polydopamine, schizopolysaccharide (average molecular weight of 30KD), and chitosan were dispersed in water and mixed evenly to obtain a mixed solution.

[0045] According to the antibacterial layer coating amount of 550g / m² 2 , the steps The mixed solution is uniformly coated onto a polypropylene substrate to form an antibacterial layer, which is then dried to obtain the final product.

[0046] The specific preparation method of the above-mentioned modified polydopamine is as follows:

[0047] a. Diatomaceous earth was added to a 10% sodium hydroxide solution and stirred at 40°C for 3 hours. After filtration and drying, it was calcined at 350°C for 2 hours to obtain pretreated diatomaceous earth. The pretreated diatomaceous earth was added to an ethanol-water solution (the volume ratio of ethanol to water in the ethanol-water solution was 4:1) at a mass ratio of 1:0.2, followed by the addition of vinyltriethoxysilane. The mixture was reacted at 55°C for 4 hours. After the reaction was completed, it was filtered, washed, and dried to obtain modified diatomaceous earth.

[0048] b. According to the mass ratio of dopamine, modified diatomaceous earth, and sodium periodate of 1:0.1:1.2, add the modified diatomaceous earth and dopamine from step a to water, stir evenly at room temperature to obtain a mixture; then add sodium periodate to the mixture and continue stirring for 60 min, filter and wash repeatedly with deionized water, and then put it into a 50℃ oven to dry for 16 h to obtain pre-modified polydopamine.

[0049] An antibacterial hernia patch was prepared using the above-described method.

[0050] (ii) Comparative Example

[0051] Comparative Example 1

[0052] The difference between Comparative Example 1 and Example 1 is that no schizopolysaccharide was added.

[0053] Comparative Example 2

[0054] The difference between Comparative Example 2 and Example 1 is that the molecular weight of the schizopolysaccharide is 5KD.

[0055] Comparative Example 3

[0056] The difference between Comparative Example 3 and Example 1 is that diatomaceous earth and polydopamine are used instead of modified polydopamine, and the mass ratio of polydopamine to diatomaceous earth is 1:0.08. The other preparation conditions are the same as in Example 1.

[0057] Comparative Example 4

[0058] The difference between Comparative Example 4 and Example 1 is that the preparation process of modified polydopamine was adjusted. Specifically, sodium periodate was not added in step b, while the other preparation conditions were the same as in Example 1.

[0059] (III) Experimental Examples

[0060] Experimental Example 1

[0061] The antibacterial effects of the hernia patches obtained in Examples 1-3 and Comparative Examples 1-4 were tested, and the specific procedures are as follows:

[0062] Prepare suspensions of Staphylococcus aureus and Escherichia coli (1×10⁻⁶) separately. 8 (CFU / mL) Take 200 μL of each of the above bacterial suspensions and evenly coat the surface of LB agar medium. Place the hernia patches (30 mm × 30 mm) obtained in Examples 1-3 and Comparative Examples 1-4 into petri dishes containing the above-mentioned culture media and incubate at 37°C for 24 h. At the same time, sterile filter paper soaked in penicillin is set up as a positive control. After the incubation, take out each group of petri dishes, and measure the distance from the center of the patch to the edge of the inhibition zone, perpendicular to the edge of the patch, starting from the center of the patch and recording it. The antibacterial effect is shown in Table 1.

[0063] Table 1

[0064]

[0065] As shown in Table 1, the hernia patches obtained in Examples 1-3 exhibit superior antibacterial effects. Compared to Examples 1-3, the antibacterial effect of the hernia patch prepared in Comparative Example 1 without omitting the schizophyllum polysaccharide is reduced. Analysis reveals that schizophyllum polysaccharide has antibacterial activity against Staphylococcus aureus and Escherichia coli; reducing the amount of schizophyllum polysaccharide used decreases the antibacterial effect of the hernia patch.

[0066] Compared to Examples 1-3, the antibacterial effect of the hernia patches prepared in Comparative Example 3 (using diatomaceous earth and replacing modified polydopamine with polydopamine) and Comparative Example 4 (changing the preparation process of modified polydopamine) was reduced. Analysis showed that the modified polydopamine was first obtained by modifying diatomaceous earth with vinyltriethoxysilane, and then utilizing the self-polymerization property of dopamine to form a polydopamine coating on the surface of the modified diatomaceous earth. The modified polydopamine formed hydrogen bonds with chitosan, enhancing its stability and antibacterial properties.

[0067] Experiment Example 2

[0068] The anti-adhesion effect of the hernia patches obtained in Examples 1-3 and Comparative Examples 1-4 was tested, and the specific process is as follows:

[0069] Experimental subjects: 35 New Zealand white rabbits, weighing 2.5-3kg, were randomly divided into 7 groups.

[0070] After anesthetizing all New Zealand white rabbits, a 20mm × 20mm layer of muscle was removed from the left abdomen. Hernia patches (30mm × 30mm) obtained in Examples 1-3 and Comparative Examples 1-4 were then implanted, fixed, and the wound sutured. Anti-adhesion performance was assessed 3 months post-surgery, including adhesion area, adhesion severity, and adhesion incidence. Vertical high-resolution images of patches with adhesions were taken and processed using Photoshop and Sicon Image software to calculate the adhesion area; grading criteria are shown in Table 2. The adhesion incidence rate was the percentage of animals with adhesions to the total number of animals in the group; anti-adhesion performance is shown in Table 2.

[0071] Table 2

[0072]

[0073] Table 2 shows that the hernia patches obtained in Examples 1-3 have a superior anti-adhesion effect. Compared with Examples 1-3, the anti-adhesion effect of the hernia patches obtained in Comparative Examples 1-4 is reduced. The above results indicate that the combined use of schizopolysaccharide and modified polydopamine can improve the anti-adhesion effect of the hernia patch.

[0074] Experimental Example 3

[0075] The cell compatibility of the hernia patches obtained in Examples 1-3 was tested, and the specific procedure is as follows:

[0076] P3 generation mouse fibroblasts L929 were used at 5 × 10 3Cells were seeded at a density of / wells in 96-well plates and cultured in complete medium (DMEM medium containing 10% FBS and 1% antibiotics) supplemented with the hernia patches (30mm × 30mm) obtained in Examples 1-3. The cells were co-cultured at 37°C and 5% CO2, with a control group consisting of pure cells. Cell proliferation was assessed using the MTS assay after 1, 3, and 5 days of culture. The cytotoxicity of the hernia patches obtained in Examples 1-3 was evaluated based on the cell proliferation rate. Cell proliferation data for each group are shown in Table 3.

[0077] Table 3

[0078]

[0079] According to the regulations of the National Medical Products Administration, when the cell proliferation rate is ≥80%, the cytotoxicity is ≤1, which meets the requirements for implantation safety. Table 3 shows that the cell proliferation rate of the hernia patches obtained in Examples 1-3 is ≥95%. These results indicate that the hernia patch obtained by this invention has excellent cell compatibility and can meet the requirements for implantation safety.

[0080] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. A method for preparing a hernia patch having an antibacterial effect, characterized by, Includes the following steps: . Disperse the modified polydopamine, the split and folded polysaccharide, and the chitosan in water, mix uniformly to obtain a mixed solution; Steps The mixed solution is uniformly coated onto the substrate to form an antibacterial layer, which is then dried to obtain the final product. The modified polydopamine is prepared as follows: a. Add pretreated diatomaceous earth to an aqueous ethanol solution, then add vinyltriethoxysilane to react. After the reaction is complete, purify to obtain modified diatomaceous earth. b. Add the modified diatomaceous earth and dopamine from step a to water and stir until homogeneous to obtain a mixture; add sodium periodate to the mixture and continue stirring until purified to obtain the final product; The average molecular weight of the slit polysaccharide is 10-30 KD.

2. The method of claim 1, wherein the hernia mesh having an antibacterial effect is prepared by adding the antibacterial agent to the mesh material. Step The mass ratio of the modified polydopamine, the laccase, the chitosan, and the water in the step (b) is (5-10):(1-5):(10-20):(25-30).

3. The method for preparing the hernia patch with antibacterial effect according to claim 1, characterized in that, In step a, the mass ratio of pretreated diatomaceous earth to vinyltriethoxysilane is 1:(0.1-0.2); the volume ratio of ethanol to water in the ethanol-water solution is 4:1; the reaction temperature is 50-55℃, and the reaction time is 4-5h.

4. The method for preparing the hernia patch with antibacterial effect according to claim 3, characterized in that, The preparation process of the pretreated diatomaceous earth is as follows: add diatomaceous earth to a sodium hydroxide solution with a mass fraction of 8-10%, stir at 30-40℃ for 3-4 hours, filter and dry, and then calcine at 300-350℃ for 2-3 hours.

5. The method for preparing the hernia patch with antibacterial effect according to claim 1, characterized in that, The mass ratio of dopamine, modified diatomaceous earth, and sodium periodate in step b is 1:(0.05-0.1):(0.8-1.2).

6. The method for preparing the hernia patch with antibacterial effect according to claim 1, characterized in that, The stirring time described in step b is 30-60 minutes.

7. The method for preparing the hernia patch with antibacterial effect according to claim 1, characterized in that, Step The coating amount of the bacteriostatic layer described in the middle is 450-550 g / m 2 .

8. The method of claim 1, wherein the mesh is prepared by the steps of: (a) providing a mesh; (b) applying a solution of a biocide to the mesh; (c) drying the mesh; and (d) applying a coating of a biocide to the mesh. Step The substrate is a polypropylene substrate.

9. A hernia patch with antibacterial properties, characterized in that, The hernia patch with antibacterial properties is prepared using the preparation method described in any one of claims 1-8.

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