Preparation method of antibacterial hydrophilic silica gel coating

Abstract

The invention belongs to the field of biomedical materials, and particularly relates to a preparation method of an antibacterial hydrophilic silica gel coating. A silica gel product is used as a matrix, surface pretreatment is firstly carried out, then the silica gel product is placed in a hydrogel solution containing antibacterial ions and / or a nano-antibacterial agent, and a coating is formed by adopting a pulling method or a soaking method. 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 introducing an antibacterial hydrophilic coating into silica gel, the antibacterial property of Cu and Zn ions or nano Cu or CuO and the hydrophilicity of hydrogel are combined, and a sterilization effect is achieved through ion release and surface contact; and meanwhile, the stimulation and friction effects of the implant on tissues are reduced, and the pain caused by friction stimulation of a patient is reduced. The silica gel coating disclosed by the invention has good biological safety, hydrophilicity and antibacterial property, and is particularly suitable for medical products such as trachea cannulas, ventricular drainage tubes, urinary catheters and the like.

Description

Technical Field

[0001] The invention belongs to the field of biomedical materials, and in particular relates to a method for preparing an antibacterial hydrophilic silica gel coating. 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 usually a hydrophobic and inert material, which 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 brings 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 solved urgently.

[0004] In order to solve such problems, the document "Preparation of Chitosan on Silicone Rubber Surface Copper Gel Coating and Its Antibacterial Function" reports a coating with anti-infection function, and 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 solutions of silane coupling agent and polyethyleneimine respectively to obtain surface amino and grafted polyethyleneimine silicone rubber, and then immerses the silicone rubber in an ethanol solution of polyvinyl pyrrolidone containing a photosensitizer, then dries and cures it under ultraviolet light to finally form a hydrophilic coating with good lubricity.

[0005] Although there are a lot of studies on antibacterial silicone coatings or hydrophilic silicone coatings in literature and patents, there are few studies on the organic combination of the two. The main difficulty is that antibacterial substances and hydrophilic substances are difficult to be compatible and cannot be effectively combined together. Summary of the invention

[0006] The purpose of the present invention is to provide a method for preparing an antibacterial hydrophilic silicone coating, and to utilize the antibacterial hydrophilicity of the coating to prevent complications caused by bacterial infection and to alleviate irritation and friction between implants and tissues.

[0007] The technical solution of the present invention is as follows:

[0008] A preparation method of an antibacterial hydrophilic silica gel coating, with a silica gel product as the substrate. First, surface pretreatment is carried out, and then it is placed in a hydrogel solution containing antibacterial ions and / or nano-antibacterial agents, and a coating is formed on its surface by the dip-coating method or the immersion method.

[0009] The preparation method of the antibacterial hydrophilic silica gel coating, the coating is a hydrogel coating, and the hydrogel includes but is not limited to gelatin, polyvinyl alcohol, hyaluronic acid or polyacrylamide.

[0010] The preparation method of the antibacterial hydrophilic silica gel coating, preferably, the antibacterial ions in the coating are Cu 2+ 、Zn 2+ , the nano-antibacterial agent in the coating is nano-Cu, CuO powder, and its particle size is 20 - 50nm, and the antibacterial component is one or more of the above.

[0011] The preparation method of the antibacterial hydrophilic silica gel coating, the preparation process of the hydrogel solution containing antibacterial components is: adding CuSO 4 or ZnSO 4 powder into the hydrogel solution to obtain a CuSO 4 and / or ZnSO 4 hydrogel solution with a concentration of 0.8 - 2.0wt%; or, adding nano-Cu and / or CuO powder or dispersion liquid into the hydrogel solution to obtain a nano-Cu and / or CuO hydrogel mixture.

[0012] The preparation method of the antibacterial hydrophilic silica gel coating, the process of surface pretreatment is: immersing the silica gel product in a dopamine-Tris-HCl solution with a concentration of 3 - 7mg / ml, placing it on a shaker and shaking for 36 - 54h, cleaning it, and then immersing it in a 2.5wt% glutaraldehyde aqueous solution for 20 - 30h and then air-drying naturally.

[0013] The preparation method of the antibacterial hydrophilic silica gel coating, the coating has a strong bactericidal function, the bactericidal rate is above 90%, effectively inhibits the adhesion of bacterial biofilms on its surface, and in addition, the coating has obvious hydrophilicity.

[0014] The preparation method of the antibacterial hydrophilic silica gel coating, the coating thickness is 1μm - 20μm.

[0015] The preparation method of the antibacterial hydrophilic silica gel coating, the coating contains antibacterial components and hydrogel, and by weight percentage, the content of each component is as follows: antibacterial component 0.3% - 2%, and the balance is hydrogel.

[0016] The design idea of the present invention is:

[0017] In view of the problems caused by silicone implants, such as infection and the irritation to the human body and the easy damage to the contacting tissues caused by hydrophobicity, the present invention proposes the idea of introducing an antibacterial hydrophilic coating on silicone. Combining the antibacterial properties of Cu, Zn ions, or nano-Cu or CuO and the hydrophilicity of hydrogel, the bactericidal effect is achieved through ion release and surface contact, while inhibiting the formation of surface bacterial biofilms. Therefore, antibacterial hydrophilic silicone is an effective measure to solve the problems of implant infection and other complications, which conforms to the current advanced medical concept and human needs and is a new direction for the development of advanced biomaterials.

[0018] The advantages and beneficial effects of the present invention are as follows:

[0019] 1. The silicone coating described in the present invention has strong antibacterial ability, can reduce the bacterial infection caused by implants, and inhibit the adhesion and proliferation of bacterial biofilms.

[0020] 2. The silicone coating described in the present invention has hydrophilicity, can reduce the irritation and friction of the implant on cell tissues, and reduce the pain of patients caused by friction and irritation.

[0021] 3. The silicone coating described in the present invention has a hemolysis rate lower than 5%, a cytotoxicity of grade 1, and good cell compatibility, meeting the biosafety requirements of implants.

[0022] 4. The silicone coating described in the present invention has good biosafety, hydrophilicity, and antibacterial properties, and is particularly suitable for medical products such as tracheal intubation tubes, ventricular drainage tubes, and urinary catheters, but is not limited to the above products. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is the morphology diagram and hydrophilicity test of the silicone catheter with coating. In the figure, ① is the silicone catheter without coating in the control group, ② is Example 1, ③ is Example 2, ④ is Example 3, and ⑤ is Example 4.

[0024] Figure 2 It is the antibacterial effect diagram of the silicone catheter with coating. In the figure, (1) is the silicone catheter without coating in the control group, (2) is Example 1, (3) is Example 2, (4) is Example 3, and (5) is Example 4. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0025] The embodiments of the present invention will be described in detail in conjunction with the accompanying drawings. This embodiment is implemented on the premise of the technical solution of the present invention, and the detailed implementation manner and specific operation process are given, but the protection scope of the present invention is not limited to the following embodiments.

[0026] Example 1

[0027] Soak a 5-cm-long silicone catheter in a dopamine-Tris-HCl solution with a concentration of 5 mg / ml (the molar concentration of Tris-HCl buffer in the solution is 50 mM, pH = 8, the same below), place it on a shaker and shake for 48 h. After cleaning, immerse it in a 2.5 wt% glutaraldehyde aqueous solution for 24 h and then air-dry it for later use. Add 30 g of gelatin particles to 300 ml of phosphate buffered saline (i.e., PBS buffer, molar concentration 0.01 M, pH = 7.2, the same below), place it on a magnetic stirrer at 60 °C and react until the gelatin is completely dissolved. Then continue to add 3.642 g of CuSO 4 powder to obtain a CuSO 4 gelatin solution with a concentration of 1.0 wt%. Place the pretreated silicone catheter in the CuSO 4 gelatin solution, and use the dip-coating method to form a coating containing Cu element and gelatin on its surface, with a coating thickness of 5.4 μm. The content of each component in this coating is as follows: the antibacterial CuSO 4 component accounts for 1.0 wt%, and the balance is gelatin.

[0028] Example 2

[0029] Soak a 5-cm-long silicone catheter in a dopamine-Tris-HCl solution with a concentration of 4 mg / ml, place it on a shaker and shake for 40 h. After cleaning, immerse it in a 2.5 wt% glutaraldehyde aqueous solution for 20 h and then air-dry it for later use. Add 30 g of gelatin particles to 300 ml of phosphate buffered saline, place it on a magnetic stirrer at 60 °C and react until the gelatin is completely dissolved. Then continue to add 3.642 g of ZnSO 4 powder to obtain a ZnSO 4 gelatin solution with a concentration of 1.0 wt%. Immerse the pretreated silicone catheter in the ZnSO 4 gelatin solution for 2 h to form a coating containing Zn element and gelatin on its surface, with a coating thickness of 3.8 μm. The content of each component in this coating is as follows: the antibacterial ZnSO 4 component accounts for 1.0 wt%, and the balance is gelatin.

[0030] Example 3

[0031] Soak a 5-cm-long silicone catheter in a dopamine-Tris-HCl solution with a concentration of 6 mg / ml, place it on a shaker and shake for 36 h. After cleaning, immerse it in a 2.5 wt% glutaraldehyde aqueous solution for 28 h and then air-dry it for later use. Add 30 g of gelatin particles to 300 ml of phosphate buffered saline, place it on a magnetic stirrer at 60 °C and react until the gelatin is completely dissolved. Then continue to add 3.642 g of CuSO 4 powder and 3.3 g of CuO powder (CuSO 4Powders of and CuO with particle sizes of 20 - 50 nm) were used to obtain CuSO solutions with a concentration of 1.0 wt% each. 4 The pre-treated silicone catheter was immersed in the mixed solution of CuSO 4 and CuO gelatin, and a coating containing Cu element and gelatin was formed on its surface by the dip-coating method, with a coating thickness of 6.9 μm. The component contents in this coating are as follows: the antibacterial CuO component accounts for 1.0 wt%, the antibacterial CuSO 4 component accounts for 1.0 wt%, and the balance is gelatin.

[0032] Example 4

[0033] A 5-cm long silicone catheter was immersed in a dopamine-Tris-HCl solution with a concentration of 3 mg / ml, placed on a shaker and shaken for 54 h. After cleaning, it was immersed in a 2.5 wt% aqueous glutaraldehyde solution for 30 h and then air-dried for later use. 30 g of gelatin particles were added to 300 ml of phosphate buffered saline solution, placed on a magnetic stirrer at 60 °C and reacted until the gelatin was completely dissolved. Then 3.3 g of CuO powder (CuO powder particle size is 20 - 50 nm) was added to obtain a CuO gelatin mixed solution with a concentration of 1.0 wt%. The pre-treated silicone catheter was immersed in the CuO gelatin mixed solution, and a coating containing Cu element and gelatin was formed on its surface by the dip-coating method, with a coating thickness of 5.1 μm. The component contents in this coating are as follows: the antibacterial CuO component accounts for 1.0 wt%, and the balance is gelatin.

[0034] Table 1 Comparison of antibacterial properties, hydrophilicity and cytotoxicity of silicone catheters

[0035] Example Antibacterial rate (%) Hydrophilic effect Cytotoxicity Hemolysis rate (%) Control group without coating 0 General Grade 1 1.5 1 91 Good Grade 1 2.1 2 92 Good Grade 1 1.9 3 98 Good Grade 1 2.6 4 94 Good Grade 1 2.3

[0036] The results of the examples show that, as shown in Table 1 and Figure 2 shown, the silicone coating of the present invention has strong antibacterial properties, can effectively kill Staphylococcus aureus and Escherichia coli (GB / T 2591), and the antibacterial rate can reach more than 90%, and can inhibit the formation of bacterial biofilms. The cytotoxicity of the coating is grade 1 (ISO-10993), and the overall hemolysis rate is less than 5%. As Figure 1 shown, compared with the silicone catheter without coating, the coating prepared by the present invention has obvious hydrophilicity effect.

Claims

1. A preparation method of an antibacterial hydrophilic silica gel coating, characterized in that, using a silica gel product as a substrate, first performing surface pretreatment, and then placing it in a hydrogel solution containing antibacterial ions and / or nano-antibacterial agents, and forming a coating on its surface by the dip-coating method or the immersion method.

2. The preparation method of the antibacterial hydrophilic silica gel coating according to claim 1, characterized in that, the coating is a hydrogel coating, and the hydrogel includes but is not limited to gelatin, polyvinyl alcohol, hyaluronic acid or polyacrylamide.

3. The preparation method of the antibacterial hydrophilic silica gel coating according to claim 1, characterized in that, Preferably, the antibacterial ions in the coating are Cu 2+ , Zn 2+ , and the nano antibacterial agent in the coating is nano Cu and CuO powder, with a particle size of 20-50 nm, and the antibacterial component is one or more of the above 4. The preparation method of the antibacterial hydrophilic silica gel coating according to claim 2 or 3, characterized in that, The preparation process of the hydrogel solution containing antibacterial components is as follows: CuSO 4 or ZnSO 4 powder is added to the hydrogel solution to obtain a CuSO 4 and / or ZnSO 4 hydrogel solution with a concentration of 0.8 - 2.0 wt%; alternatively, nano-Cu and / or CuO powder or dispersion liquid is added to the hydrogel solution to obtain a nano-Cu and / or CuO hydrogel mixture.

5. The preparation method of the antibacterial hydrophilic silica gel coating according to claim 1, characterized in that, the process of surface pretreatment is: soaking the silica gel product in a dopamine-Tris-HCl solution with a concentration of 3-7 mg / ml, placing it on a shaker and shaking for 36-54 h, cleaning it, and then immersing it in a 2.5 wt% aqueous glutaraldehyde solution for 20-30 h and then air-drying naturally.

6. The preparation method of the antibacterial hydrophilic silica gel coating according to claim 1, characterized in that, the coating has a strong bactericidal function, the bactericidal rate is more than 90%, effectively inhibits the adhesion of bacterial biofilms on its surface, and in addition, the coating has obvious hydrophilicity.

7. The preparation method of the antibacterial hydrophilic silica gel coating according to claim 1, characterized in that, the coating thickness is 1 μm - 20 μm.

8. The preparation method of the antibacterial hydrophilic silica gel coating according to claim 1, characterized in that, the coating contains antibacterial components and hydrogel, and by weight percentage, the content of each component is as follows: antibacterial components 0.3% - 2%, and the balance is hydrogel.

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