Preparation method of integral antibacterial hydrophilic silica gel

Abstract

The invention belongs to the field of biomedical materials, and particularly relates to a preparation method of integral antibacterial hydrophilic silica gel. Aiming at the problems of infection caused by a silica gel implant, stimulation to a human body caused by hydrophobicity, easy damage to contact tissues and the like, the invention provides a thought of adding a proper amount of functional antibacterial hydrophilic elements into a silica gel matrix, and a proper processing technology is adopted to form an integral antibacterial hydrophilic silica gel material or product. The composition can prevent complications caused by bacterial infection and relieve stimulation and friction between implants and tissues, achieves a sterilization effect through continuous release and surface contact, inhibits formation of surface bacterial biofilms, and reduces pains of patients caused by friction stimulation. The integral silica gel disclosed by the invention has good biological safety, hydrophilicity and antibacterial property, and is particularly suitable for medical products taking silica gel as a base material.

Description

Technical Field

[0001] The invention belongs to the field of biomedical materials, and in particular relates to a method for preparing integral antibacterial hydrophilic silica gel. Background Art

[0002] Medical grade silicone rubber has good biocompatibility, is non-irritating, non-toxic, non-allergic to human tissues, and has very little rejection reaction from the body; it has good physical and chemical properties, can maintain its original elasticity and softness in contact with body fluids and tissues, and is not degraded. It is a stable substance. Its products have been widely used in products such as pacemakers, heart valves, breast prostheses, finger joints, orbital bases, endotracheal tubes, auricles, hydrocephalus drainage tubes, peritoneal dialysis tubes, balloon-bearing split-channel catheters and urinary catheters.

[0003] However, silicone rubber is an inert material and is extremely susceptible to bacterial infection during the implantation process. Once such a disease occurs, it is usually difficult to control and recurs repeatedly, which can lead to local tissue damage, systemic spread of pathogens, and implant failure. In addition, the strong hydrophobicity of the silicone rubber surface makes it have poor adhesion to tissues and cells and high friction, which causes great irritation and contact tissue damage to patients. Therefore, infections caused by silicone implants and clinical pain points caused by hydrophobicity are important issues that need to be addressed.

[0004] The existing method for preparing antibacterial or hydrophilic silica gel is mainly achieved through surface modification.

[0005] The Chinese patent application with publication number: CN115160928A discloses an antibacterial silicone rubber coating, a preparation method and an application thereof. The antibacterial silicone rubber coating of the invention is based on a cross-linked network formed by vinylmethylphenylpolysiloxane and mercaptopropylmethylphenylpolysiloxane, and is matched with a photosensitive silicone resin containing polysulfide bonds and modified nanoparticles. The roughness of the modified nanoparticles and the low surface energy of the silicone material are combined to make the surface of the antibacterial silicone rubber coating have super hydrophobic properties, thereby effectively preventing biological adhesion and achieving sustainable antibacterial properties.

[0006] The Chinese patent application with publication number: CN105601933A discloses a method for preparing a hydrophilic coating on the surface of silicone rubber. The invention immerses the silicone rubber material in a solution of a silane coupling agent and polyethyleneimine respectively to obtain surface amino-modified and grafted polyethyleneimine silicone rubber, and then immerses the silicone rubber in an ethanol solution of polyvinyl pyrrolidone containing a photosensitizer, dries it, and cures it under ultraviolet light, finally forming a hydrophilic coating with good lubricity.

[0007] From the above public information, the usual way to prepare a silica gel functional coating is to introduce reactive groups on its surface, and then graft functional reagents onto the surface of silica gel through specific reactive groups to prepare functional silica gel. However, the surface modification method requires complex secondary process flows. Generally, reactive groups are introduced through plasma technology. The cost of using this surface modification technology is relatively high, and it is difficult to achieve the uniformity and stability of the coating for capillary-shaped silica gel tubes, and the pipeline is prone to blockage. In addition, there are problems such as unstable coating performance caused by poor binding force or poor coating thickness uniformity in the coating functionality. Therefore, this method is not suitable for preparing silicone rubber products with large demand or silica gel products with complex shapes and internal channels.

[0008] The Chinese patent application with the publication number CN113774262A discloses an antibacterial silicone rubber and its preparation method. The silicone rubber is added with a triblock polyorganosiloxane quaternary ammonium salt, which has good compatibility with the silicone rubber and can be chemically crosslinked into the silica gel matrix to obtain a long-lasting antibacterial silica gel material. Such integral antibacterial silica gel materials provide a possibility to a certain extent for solving the preparation of silica gel with large demand and special complex shapes. However, there are still certain technical problems in how to effectively combine antibacterial properties and hydrophilic properties in the silica gel matrix. Therefore, with the improvement of medical concepts, developing stable and long-lasting anti-infective and hydrophilic integral silica gel materials and their products is the development trend of the new generation of medical silicone products. Summary of the Invention

[0009] The purpose of the present invention is to provide a preparation method of integral antibacterial hydrophilic silica gel. By adding a certain proportion of functional elements to silica gel and adopting a suitable processing technology, an integral antibacterial hydrophilic silica gel material or product is formed to prevent complications caused by bacterial infection and relieve the irritation and friction between the implant and the tissue.

[0010] The technical solution of the present invention is as follows:

[0011] A preparation method of integral antibacterial hydrophilic silica gel, adding functional elements to silica gel raw materials, the functional elements being nano-Cu powder, nano-CuO powder or their dispersions, and adopting the processing technology of silica gel to form an integral antibacterial hydrophilic silica gel material or product.

[0012] In the preparation method of the integral antibacterial hydrophilic silica gel described above, the silica gel raw materials are liquid silica gel or silica gel solid raw materials.

[0013] In the preparation method of the integral antibacterial hydrophilic silica gel described above, the addition of the functional elements plays an antibacterial role and a surface hydrophilic role, and the addition ratio is 0.3 - 0.6 wt% of the silica gel raw materials.

[0014] The preparation method of the integral antibacterial hydrophilic silica gel is as follows: First, the silica gel raw material and the functional elements are mixed. For liquid silica gel, it is directly added and stirred evenly by magnetic force, and then injection molded. For products with higher performance requirements, the solid silica gel raw material and the functional elements are physically mixed evenly by a two-roll rubber mixer, and the required product shape is prepared through plastic deformation, and then high-temperature vulcanization is carried out to obtain the final product.

[0015] The preparation method of the integral antibacterial hydrophilic silica gel. This integral antibacterial hydrophilic silica gel has a strong and continuous bactericidal function, with a bactericidal rate of over 90%, effectively killing bacteria and thus preventing the adhesion of bacterial biofilms on its surface.

[0016] The preparation method of the integral antibacterial hydrophilic silica gel. This integral antibacterial hydrophilic silica gel has obvious hydrophilicity.

[0017] The design concept of the present invention is:

[0018] Aiming at the problems of infection caused by silicone implants and irritation to the human body and easy damage to the contacting tissues caused by hydrophobicity, the present invention proposes the idea of adding an appropriate amount of functionalized antibacterial hydrophilic elements (such as: nano-copper oxide or nano-copper and their dispersions, mainly playing antibacterial and surface hydrophilic roles) to the silicone matrix, and adopting a suitable processing technology to form an integral antibacterial hydrophilic silica gel material or product, preventing complications caused by bacterial infection and alleviating the irritation and friction between the implant and the tissue. In particular, the bactericidal effect is achieved through the continuous release of Cu ions and surface contact, and the formation of surface bacterial biofilms is inhibited. At the same time, the irritation and friction of the implant on the tissue are reduced, and the pain of the patient caused by friction irritation is reduced. Therefore, the development of a stable and long-lasting anti-infective and hydrophilic integral silica gel material and its products by the present invention is an urgent need for a new generation of medical silicone products, meeting the current advanced medical concepts and human needs, and is a new direction for the development of advanced biomaterials.

[0019] The advantages and beneficial effects of the present invention are:

[0020] 1. The silica gel described in the present invention is an integral performance functionalized material, having stable, persistent and strong antibacterial ability, which can reduce bacterial infections caused by implants and inhibit the adhesion and proliferation of bacterial biofilms.

[0021] 2. The integral antibacterial hydrophilic silica gel of the present invention has hydrophilicity, which can reduce the irritation and friction of the implant on the cell tissue and reduce the pain of the patient caused by friction irritation.

[0022] 3. The integral antibacterial hydrophilic silica gel of the present invention has a hemolysis rate of less than 5% and a cytotoxicity of grade 1, with good cell compatibility, meeting the biosafety requirements of implants.

[0023] 4. The integrally antibacterial and hydrophilic silica gel of the present invention is suitable for preparing silicone rubber products with large demand or silicone products with complex shapes, such as medical products like endotracheal intubation tubes, ventricular drainage tubes, urinary catheters, etc., but is not limited to the above products. Description of the Drawings

[0024] Figure 1 It is the morphology diagram and hydrophilic effect diagram of the silica gel material. In the figure, (1) is the silica gel without adding functional elements in the control group, (2) is Example 1, and (3) is Example 2.

[0025] Figure 2 It is the antibacterial effect diagram of the silica gel material. In the figure, (1) is the silica gel without adding functional elements in the control group, (2) is Example 1, (3) is Example 2, and (4) is Example 3. Detailed Embodiments

[0026] The embodiments of the present invention will be described in detail with reference to the accompanying drawings. These embodiments are implemented on the premise of the technical solution of the present invention, and detailed implementation manners and specific operation processes are given. However, the protection scope of the present invention is not limited to the following embodiments.

[0027] Example 1

[0028] Mix liquid silicone A and B evenly in a weight ratio of 1:1 to form AB liquid silicone. Then, mix nano-CuO powder (the particle size of CuO powder is 20 - 50 nm) with the silicone in a ratio of 0.4 wt%, and use magnetic stirring for 3 min until the nano-CuO powder is evenly dispersed in the liquid silicone. After injection molding and standing for 24 h, it is prepared into a molded product.

[0029] Example 2

[0030] Mix liquid silicone A and B evenly in a weight ratio of 1:1 to form AB liquid silicone. Take an aqueous dispersion of nano-CuO powder with a concentration of 20 wt% (the particle size of CuO powder is 20 - 50 nm), and mix it with the silicone in a ratio of 0.5 wt% based on the content of nano-copper oxide. Use magnetic stirring for 3 min until the nano-CuO dispersion is evenly dispersed in the liquid silicone. After injection molding and standing for 24 h, it is prepared into a molded product.

[0031] Example 3

[0032] Mix nano-Cu powder (the particle size of Cu powder is 20 - 50 nm) with the silicone solid raw material in a ratio of 0.3 wt% in a two-roll rubber mixer and mix evenly physically. Then, add vulcanizing agent and vulcanization accelerator for mixing. After discharging, the rubber compound is obtained, and the rubber compound is pressed into sheets and then vulcanized to obtain modified silicone.

[0033] Table 1 Comparison of antibacterial performance, hydrophilicity and cytotoxicity of silica gel

[0034] Example Antibacterial rate (%) Hydrophilic effect Cytotoxicity Hemolysis rate (%) Control group 0 General Grade 1 1.5 1 93 Good Grade 1 2.1 2 94 Good Grade 1 1.9 3 91 Good Grade 1 1.7

[0035] The results of the examples show that in combination with Figure 1 and Figure 2 and Table 1, compared with the silica gel without addition, the silica gel of the present invention has strong antibacterial properties and hydrophilic effects, can effectively kill Staphylococcus aureus and Escherichia coli (GB / T 2591), the antibacterial rate can reach more than 90%, and can inhibit the formation of bacterial biofilms. The cytotoxicity is Class 1 (ISO-10993), and the hemolysis rate is less than 5% as a whole. Therefore, the overall antibacterial hydrophilic silica gel of the present invention has good biosafety, hydrophilicity and antibacterial properties, and is particularly suitable for medical products based on silica gel.

Claims

1. Preparation method of an integral antibacterial hydrophilic silica gel, characterized in that, functional elements are added to the silica gel raw material, and the functional elements are nano-Cu powder, nano-CuO powder or their dispersions, and an integral antibacterial hydrophilic silica gel material or product is formed by using the processing technology of silica gel.

2. The preparation method of the integral antibacterial hydrophilic silica gel according to claim 1, characterized in that, the silica gel raw material is liquid silica gel or silica gel solid raw material.

3. The preparation method of the integral antibacterial hydrophilic silica gel according to claim 1, characterized in that, the addition of the functional element plays an antibacterial role and a surface hydrophilic role, and the addition ratio is 0.3-0.6 wt% of the silica gel raw material.

4. The preparation method of the integral antibacterial hydrophilic silica gel according to claim 1, characterized in that, firstly, the silica gel raw material and the functional element are mixed. For liquid silica gel, it is directly added and stirred evenly by magnetic force, and then injection molded; for products with higher performance requirements, the silica gel solid raw material and the functional element are physically mixed evenly by a two-roll rubber mixer, and the shape of the required product is prepared by plastic deformation, and then high-temperature vulcanization is carried out to obtain the final product.

5. The preparation method of the integral antibacterial hydrophilic silica gel according to any one of claims 1 to 4, characterized in that, the integral antibacterial hydrophilic silica gel has a strong continuous bactericidal function, the bactericidal rate is more than 90%, and bacteria are effectively killed to prevent the adhesion of bacterial biofilms on its surface.

6. The preparation method of the integral antibacterial hydrophilic silica gel according to any one of claims 1 to 4, characterized in that, the integral antibacterial hydrophilic silica gel has obvious hydrophilicity.

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