Medical efficient antibacterial silicone rubber and preparation method thereof

Abstract

The invention discloses medical efficient antibacterial silicone rubber and a preparation method thereof, and belongs to the technical field of medical silicone rubber materials.The preparation method comprises the following steps that 1, tannic acid is added into N, N-dimethylformamide and stirred to be uniform, then triethylamine is added, stirring continues to be conducted to be uniform, acryloyl chloride is added under the ice-water bath condition, stirring is conducted for a reaction, and a reaction solution is obtained; performing reduced pressure distillation, centrifugation, washing and vacuum drying to obtain modified tannic acid; step 2, carrying out surface activation treatment on the silicone rubber; step 3, adding the surface-activated silicone rubber and an initiator into acetone, heating and stirring for reaction, filtering and washing, and naturally drying to obtain pretreated silicone rubber; and step 4, mixing the modified tannic acid aqueous solution and the pretreated silicone rubber, and performing ultraviolet light illumination and cleaning to obtain the silicone rubber. The obtained silicone rubber has excellent antibacterial performance, and the preparation method is simple, mild in condition and suitable for large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of medical silicone rubber materials, and in particular relates to a medical high-efficiency antibacterial silicone rubber and a preparation method thereof. Background Art

[0002] In recent years, with the vigorous development of science and technology and medical industry, the demand for biomedical materials has also increased rapidly, and higher requirements have been put forward for the use characteristics of biomedical materials. Silicone rubber materials are widely used in the field of biomedical materials due to their low toxicity and good mechanical properties.

[0003] However, since silicone rubber materials are usually in direct contact with human tissue during use, a large number of bacteria will be adsorbed on the surface of silicone rubber, causing bacterial infection in the human body, which greatly limits the application of silicone rubber in clinical medicine. At present, commercial antibacterial medical silicone rubber products are still mainly based on release-type antibacterial surfaces such as antibiotics. However, in the process of releasing antibacterial components, there is often a problem of "explosive release" in the early stage and slow release in small amounts in the later stage, which makes it difficult to achieve long-term antibacterial effects; on the other hand, the disordered and excessive release of antibiotics and silver can easily cause drug resistance. In the patent document with publication number CN109912982A, a graphene quantum dot-coated nanosilver antibacterial agent solution is added to liquid silicone rubber, and a biomedical silicone rubber with good antibacterial properties is obtained by curing. However, the antibacterial nanosilver is continuously dissolved and accumulated in the environment, producing cytotoxicity, resulting in the lack of good biocompatibility of the material and high cost. In the patent document with publication number CN110128828A, a chemical reduction method is used to prepare a composite antibacterial agent using an aldehyde-containing aqueous solution as a reducing agent and β-CD as a stabilizer. The antibacterial silicone rubber is obtained by adding the composite antibacterial agent to liquid silicone rubber through physical blending. The prepared antibacterial silicone rubber has good antibacterial properties. However, physical blending easily leads to weak bonding between the antibacterial coating and the material surface, poor stability, and is not conducive to the long-term antibacterial effect.

[0004] Therefore, developing a medical silicone rubber material with high antibacterial properties is an urgent problem to be solved. Summary of the invention

[0005] The purpose of the present invention is to provide a medical high-efficiency antibacterial silicone rubber and a preparation method thereof, so as to solve the problem that the antibacterial performance of medical silicone rubber materials is poor.

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

[0007] The first aspect of the present invention provides a method for preparing a medical high-efficiency antibacterial silicone rubber, comprising the following steps:

[0008] Step 1, adding tannic acid to N,N-dimethylformamide, stirring evenly, then adding triethylamine, continuing to stir until evenly, adding acryloyl chloride under ice water bath conditions, stirring and reacting for 22-24 hours, distilling under reduced pressure, centrifuging, washing, and vacuum drying to obtain modified tannic acid;

[0009] Step 2, performing surface activation treatment on the silicone rubber;

[0010] Step 3, adding the surface activated silicone rubber and initiator into acetone, heating to 36-38° C., stirring for reaction for 2-3 hours, filtering, washing, and naturally drying to obtain the pretreated silicone rubber;

[0011] Step 4: Mix the modified tannic acid aqueous solution and the pretreated silicone rubber, irradiate with ultraviolet light, and wash to obtain silicone rubber.

[0012] As a further embodiment of the present invention, in step 1, the usage ratio of tannic acid, N,N-dimethylformamide, triethylamine and acryloyl chloride is 12.75-13.00 g: 150 mL: 27 mL: 16.9-17.0 g.

[0013] As a further solution of the present invention, the specific method of the surface activation treatment in step 2 is: using a plasma treatment method to activate the silicone rubber. By using plasma technology to treat the surface of the silicone rubber, a large number of active groups are generated on the surface, thereby improving the reaction activity of the silicone rubber.

[0014] As a further solution of the present invention, in step 3, the usage ratio of the surface activated silicone rubber, the initiator and the acetone is 4.8-5.0 g: 0.5-0.8 g: 100 mL.

[0015] As a further embodiment of the present invention, the initiator in step 3 is benzoin dimethyl ether, benzophenone or a mixture of both.

[0016] As a further embodiment of the present invention, in step 4, the usage ratio of the modified tannic acid aqueous solution and the pretreated silicone rubber is 40-50 mL: 3.0-4.0 g.

[0017] As a further embodiment of the present invention, the concentration of the modified tannic acid aqueous solution in step 4 is 0.1-0.3 g / mL.

[0018] As a further solution of the present invention, the ultraviolet light irradiation time in step 4 is 3-5 minutes.

[0019] The second aspect of the present invention provides a medical high-efficiency antibacterial silicone rubber obtained by the preparation method described in the first aspect.

[0020] Beneficial effects of the present invention:

[0021] The present invention combines two surface modification methods of plasma treatment and photoinitiator-induced grafting, so that the antibacterial property of the prepared silicone rubber is more stable, not easy to fall off, and can maintain the antibacterial property for a long time, and has good application prospects.

[0022] In the present invention, a modified tannic acid molecular chain is introduced into the silicone rubber, and a tannic acid coating layer is further formed on the silicone rubber surface. On the one hand, the surface hydrophilicity of the silicone rubber is further improved. This is because the modified tannic acid is introduced into the silicone rubber matrix to form a semi-interpenetrating system. In addition, the modified tannic acid contains polar groups such as phenolic hydroxyl groups and carbonyl groups, which have good hydrophilic properties. Therefore, the surface hydrophilicity of the silicone rubber material is significantly improved, and the bacterial adhesion phenomenon caused by the strong hydrophobicity of the silicone rubber is reduced. On the other hand, the molecular structure of the modified tannic acid has a large number of phenolic hydroxyl groups and has excellent broad-spectrum antibacterial activity. After the photo-initiated grafting reaction with the pretreated silicone rubber, a large number of antibacterial functional groups are introduced, which significantly improves the antibacterial properties of the silicone rubber and can maintain the antibacterial properties for a long time.

[0023] The preparation method of the medical high-efficiency antibacterial silicone rubber provided by the invention is simple, the conditions are mild, and it is suitable for industrial promotion and application. DETAILED DESCRIPTION

[0024] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. 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

[0026] This embodiment provides a method for preparing medical high-efficiency antibacterial silicone rubber, comprising the following steps:

[0027] Step 1, add 12.75g of tannic acid to 150mL of N,N-dimethylformamide, stir evenly, then add 27mL of triethylamine, continue stirring until evenly, add 16.9g of acryloyl chloride under ice-water bath conditions, stir and react for 24h, distill under reduced pressure, centrifuge, wash with anhydrous ethanol 3 times, and finally dry in a vacuum drying oven at 80°C for 24h to obtain modified tannic acid;

[0028] Step 2, treating the silicone rubber with oxygen atmosphere plasma;

[0029] Step 3, add 4.8 g of surface activated silicone rubber and 0.5 g of benzoin dimethyl ether into 100 mL of acetone, heat to 36° C., stir to react for 2 h, filter, wash, and naturally dry to obtain pretreated silicone rubber;

[0030] Step 4: Mix 40 mL of modified tannic acid aqueous solution (0.1 g / mL) and 3.0 g of pretreated silicone rubber, irradiate with ultraviolet light for 3 minutes, and then ultrasonically clean the polymerized silicone rubber in an ethanol aqueous solution (50 wt%) for 5 minutes to obtain silicone rubber.

[0031] The medical high-efficiency antibacterial silicone rubber is prepared by the above steps.

[0032] Example 2

[0033] Compared with Example 1, the only difference is:

[0034] Step 1: Add 12.75 g of tannic acid to 150 mL of N,N-dimethylformamide, stir evenly, then add 27 mL of triethylamine, continue stirring until evenly mixed, add 17.0 g of acryloyl chloride in an ice-water bath, stir and react for 24 hours, distill under reduced pressure, centrifuge, wash 3 times with anhydrous ethanol, and finally dry in a vacuum drying oven at 80°C for 24 hours to obtain modified tannic acid.

[0035] Example 3

[0036] Compared with Example 1, the only difference is:

[0037] Step 1, add 13.00g tannic acid to 150mL N,N-dimethylformamide, stir evenly, then add 27mL triethylamine, continue stirring until evenly, add 17.0g acryloyl chloride in an ice water bath, stir and react for 24h, distill under reduced pressure, centrifuge, wash 3 times with anhydrous ethanol, and finally dry in a vacuum drying oven at 80°C for 24h to obtain modified tannic acid.

[0038] Example 4

[0039] Compared with Example 1, the only difference is:

[0040] Step 3: Add 5.0 g of surface activated silicone rubber and 0.8 g of benzoin dimethyl ether into 100 mL of acetone, heat to 36° C., stir to react for 2 h, filter and wash, and naturally dry to obtain the pretreated silicone rubber.

[0041] Example 5

[0042] Compared with Example 1, the only difference is:

[0043] Step 4: Mix 40 mL of modified tannic acid aqueous solution (0.28 g / mL) and 3.0 g of pretreated silicone rubber, irradiate with ultraviolet light for 3 minutes, and then ultrasonically clean the polymerized silicone rubber in an ethanol aqueous solution (50 wt%) for 5 minutes to obtain silicone rubber.

[0044] Example 6

[0045] Compared with Example 1, the only difference is:

[0046] Step 4: Mix 50 mL of modified tannic acid aqueous solution (0.2 g / mL) and 4.0 g of pretreated silicone rubber, irradiate with ultraviolet light for 5 minutes, and then ultrasonically clean the polymerized silicone rubber in an ethanol aqueous solution (50 wt%) for 8 minutes to obtain silicone rubber.

[0047] Comparative Example 1

[0048] This comparative example provides a method for preparing a medical high-efficiency antibacterial silicone rubber, comprising the following steps:

[0049] Step 1, add 12.75g of tannic acid to 150mL of N,N-dimethylformamide, stir evenly, then add 27mL of triethylamine, continue stirring until evenly, add 16.9g of acryloyl chloride under ice-water bath conditions, stir and react for 24h, distill under reduced pressure, centrifuge, wash with anhydrous ethanol 3 times, and finally dry in a vacuum drying oven at 80°C for 24h to obtain modified tannic acid;

[0050] Step 2, add 4.8 g of surface activated silicone rubber and 0.5 g of benzoin dimethyl ether into 100 mL of acetone, heat to 36° C., stir to react for 2 h, filter, wash, and naturally dry to obtain pretreated silicone rubber;

[0051] Step 3: Mix 40 mL of modified tannic acid aqueous solution (0.1 g / mL) and 3.0 g of pretreated silicone rubber, irradiate with ultraviolet light for 3 minutes, and then ultrasonically clean the polymerized silicone rubber in an ethanol aqueous solution (50 wt%) for 5 minutes to obtain silicone rubber.

[0052] The medical high-efficiency antibacterial silicone rubber is prepared by the above steps.

[0053] Comparative Example 2

[0054] Step 1, treating the silicone rubber with oxygen atmosphere plasma;

[0055] Step 2, add 4.8 g of surface activated silicone rubber and 0.5 g of benzoin dimethyl ether into 100 mL of acetone, heat to 36° C., stir to react for 2 h, filter, wash, and naturally dry to obtain pretreated silicone rubber;

[0056] Step 3: Mix 40 mL of tannic acid aqueous solution (0.1 g / mL) and 3.0 g of pretreated silicone rubber, irradiate with ultraviolet light for 3 min, and then ultrasonically clean the polymerized silicone rubber in an ethanol aqueous solution (50 wt%) for 5 min to obtain silicone rubber.

[0057] The medical high-efficiency antibacterial silicone rubber is prepared by the above steps.

[0058] Comparative Example 3

[0059] Compared with Example 1, the only difference is:

[0060] Step 1: Add 11.5 g of tannic acid to 150 mL of N,N-dimethylformamide, stir evenly, then add 27 mL of triethylamine, continue stirring until evenly mixed, add 16.9 g of acryloyl chloride in an ice-water bath, stir and react for 24 hours, distill under reduced pressure, centrifuge, wash 3 times with anhydrous ethanol, and finally dry in a vacuum drying oven at 80°C for 24 hours to obtain modified tannic acid.

[0061] Comparative Example 4

[0062] Compared with Example 1, the only difference is:

[0063] Step 1. Add 12.75 g of tannic acid to 150 mL of N,N-dimethylformamide, stir evenly, then add 27 mL of triethylamine, continue stirring until evenly mixed, add 16.6 g of acryloyl chloride in an ice-water bath, stir and react for 24 hours, distill under reduced pressure, centrifuge, wash 3 times with anhydrous ethanol, and finally dry in a vacuum drying oven at 80°C for 24 hours to obtain modified tannic acid.

[0064] Comparative Example 5

[0065] Compared with Example 1, the only difference is:

[0066] Step 3: Add 4.6 g of surface activated silicone rubber and 0.5 g of benzoin dimethyl ether into 100 mL of acetone, heat to 36° C., stir to react for 2 h, filter and wash, and naturally dry to obtain the pretreated silicone rubber.

[0067] Comparative Example 6

[0068] Compared with Example 1, the only difference is:

[0069] Step 3: Add 5.2 g of surface activated silicone rubber and 0.5 g of benzoin dimethyl ether into 100 mL of acetone, heat to 36° C., stir to react for 2 h, filter and wash, and naturally dry to obtain the pretreated silicone rubber.

[0070] Comparative Example 7

[0071] Compared with Example 1, the only difference is:

[0072] Step 4: Mix 30 mL of modified tannic acid aqueous solution (0.1 g / mL) and 3.0 g of pretreated silicone rubber, irradiate with ultraviolet light for 3 minutes, and then ultrasonically clean the polymerized silicone rubber in an ethanol aqueous solution (50 wt%) for 5 minutes to obtain silicone rubber.

[0073] Comparative Example 8

[0074] Compared with Example 1, the only difference is:

[0075] Step 4: Mix 60 mL of modified tannic acid aqueous solution (0.1 g / mL) and 3.0 g of pretreated silicone rubber, irradiate with ultraviolet light for 3 minutes, and then ultrasonically clean the polymerized silicone rubber in an ethanol aqueous solution (50 wt%) for 5 minutes to obtain silicone rubber.

[0076] Comparative Example 9

[0077] Compared with Example 1, the only difference is:

[0078] Step 4: Mix 40 mL of modified tannic acid aqueous solution (0.1 g / mL) and 3.0 g of pretreated silicone rubber, irradiate with ultraviolet light for 8 min, and then ultrasonically clean the polymerized silicone rubber in an ethanol aqueous solution (50 wt%) for 5 min to obtain silicone rubber.

[0079] The antibacterial performance of Examples 1 to 6 and Comparative Examples 1 to 9 was tested:

[0080] Preparation of bacterial solution: Weigh 3g of tryptone soy broth and dissolve it in 100mL of ultrapure water to prepare bacterial liquid culture medium (TSB); aspirate 4mL of liquid culture medium, add 40μL of frozen bacterial solution, and then place it in a 37℃ constant temperature shaker for 24h to obtain activated bacterial solution. The activated bacterial solution was centrifuged at 3000r / min for 10min, the upper liquid was discarded, and 4mL of sterilized TSB was added to mix the bacterial solution evenly. The concentration of the bacterial solution was quantified by UV-visible spectrophotometer, and the bacterial solution was diluted to a concentration of 10 with TSB as the solvent. 6 CFU / mL.

[0081] The silicone rubber obtained in the examples and comparative examples was cut into discs with a diameter of 9 mm (three parallel samples in each group), sterilized in 75% alcohol for 30 min, and then the alcohol on the surface of the material was washed off in sterile PBS. Then 5 μL of 10 6 The bacterial solution of CFU / mL was evenly distributed on the surface of each silicone rubber, and immediately placed in a constant temperature (37°C) and constant humidity (75%) incubator for 2 hours. After 2 hours, the material was placed in 1 mL of sterilized PBS and ultrasonically treated for 5 minutes to elute the bacteria on the surface of the material into PBS. After mixing evenly, it was diluted step by step to the appropriate concentration with a 10-fold concentration gradient, and 200 μL of liquid was evenly applied to the surface of the agar culture plate, and then the agar culture plate inoculated with bacteria was placed in a constant temperature and humidity incubator for 24 hours to allow the bacteria on the agar plate to proliferate into colonies visible to the naked eye, and the number of colonies was counted. The colonies growing on the agar culture plate were observed and photographed, and the antibacterial rate was calculated. The antibacterial rate results are shown in Table 1.

[0082] Table 1

[0083]

[0084]

[0085] It can be seen from Table 1 that the antibacterial rates against Escherichia coli and Staphylococcus aureus in Comparative Examples 1-9 are lower than those in Examples 1-6. It can be seen that the silicone rubber prepared in the present invention has excellent antibacterial properties, and the preparation method is simple, the conditions are mild, and it is suitable for large-scale production.

[0086] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprises" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0087] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a medical high-efficiency antibacterial silicone rubber, characterized in that: Step 1, adding tannic acid to N,N-dimethylformamide, stirring evenly, then adding triethylamine, continuing to stir until evenly, adding acryloyl chloride under ice water bath conditions, stirring and reacting for 22-24 hours, distilling under reduced pressure, centrifuging, washing, and vacuum drying to obtain modified tannic acid; Step 2, performing surface activation treatment on the silicone rubber; Step 3, adding the surface activated silicone rubber and initiator into acetone, heating to 36-38° C., stirring for reaction for 2-3 hours, filtering, washing, and naturally drying to obtain the pretreated silicone rubber; Step 4: Mix the modified tannic acid aqueous solution and the pretreated silicone rubber, irradiate with ultraviolet light, and wash to obtain silicone rubber.

2. The method for preparing a medical high-efficiency antibacterial silicone rubber according to claim 1, characterized in that: In step 1, the dosage ratio of tannic acid, N,N-dimethylformamide, triethylamine and acryloyl chloride is 12.75-13.00 g: 150 mL: 27 mL: 16.9-17.0 g.

3. The method for preparing a medical high-efficiency antibacterial silicone rubber according to claim 1, characterized in that: The specific method of the surface activation treatment in step 2 is: using a plasma treatment method to activate the silicone rubber.

4. The method for preparing a medical high-efficiency antibacterial silicone rubber according to claim 1, characterized in that: In step 3, the usage ratio of the surface activated silicone rubber, the initiator and the acetone is 4.8-5.0 g: 0.5-0.8 g: 100 mL.

5. The method for preparing a medical high-efficiency antibacterial silicone rubber according to claim 1, characterized in that: The initiator in step 3 is one or a mixture of dimethyl benzoate and benzophenone.

6. The method for preparing a medical high-efficiency antibacterial silicone rubber according to claim 1, characterized in that: In step 4, the usage ratio of the modified tannic acid aqueous solution and the pretreated silicone rubber is 40-50 mL: 3.0-4.0 g.

7. The method for preparing a medical high-efficiency antibacterial silicone rubber according to claim 1, characterized in that: The concentration of the modified tannic acid aqueous solution in step 4 is 0.1-0.3 g / mL.

8. The method for preparing a medical high-efficiency antibacterial silicone rubber according to claim 1, characterized in that: In step 4, the ultraviolet light irradiation time is 3-5 minutes.

9. A medical high-efficiency antibacterial silicone rubber, characterized in that: Prepared by the preparation method according to any one of claims 1 to 8.

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