Antibacterial coating with pH monitoring function, functional material of antibacterial coating with pH monitoring function and preparation method of functional material
阅读说明：本技术 一种具有pH监测功能的抗菌涂层、具有pH监测功能的抗菌涂层的功能材料及其制备方法 (Antibacterial coating with pH monitoring function, functional material of antibacterial coating with pH monitoring function and preparation method of functional material ) 是由 闫顺杰 孙振龙 栾世方 殷敬华 周容涛 杨华伟 班雨 万雪 李君� 陈寿松 于 2019-10-14 设计创作，主要内容包括：本发明提供了一种具有pH监测功能的抗菌涂层,包括有机硅季铵盐pyranine化合物；所述有机硅季铵盐pyranine化合物由8-羟基-1,3,6-芘三磺酸三钠盐和有机硅季铵盐经反应后得到；所述有机硅季铵盐具有式(I)所示结构。涂层中的有机硅季铵盐的硅氧烷基团可以分别与pyranine分子、羟基化处理的基体材料表面发生化学键键连,不仅涂层内部的pyranine和有机硅季铵盐相互交联,提高涂层自身稳定性,同时涂层与被涂基体实现交联点式的化学键交联,大大提升了涂层和被涂基体的稳定性,pH监测和抗菌效果更加持久。本发明制备过程更加简单,易操作,可行性高。<Image he="254" wi="700" file="DDA0002232725300000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention provides an antibacterial coating with a pH monitoring function, which comprises an organosilicon quaternary ammonium salt pyranine compound; the organosilicon quaternary ammonium salt pyranine compound is obtained by reacting 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt; the organosilicon quaternary ammonium salt has a structure shown in a formula (I). The siloxane groups of the organosilicon quaternary ammonium salt in the coating can be respectively reacted with pyranine molecules and hydroxylatedThe surface of the base material is chemically bonded, and not only is the pyranine and the organosilicon quaternary ammonium salt in the coating crosslinked with each other, so that the stability of the coating is improved, but also the coating and the coated base body are crosslinked in a crosslinking point mode, so that the stability of the coating and the coated base body is greatly improved, and the pH monitoring and antibacterial effects are more durable. The preparation process is simpler, the operation is easy, and the feasibility is high.)
1. An antibacterial coating with a pH monitoring function is characterized by comprising an organosilicon quaternary ammonium salt pyranine compound;
the organosilicon quaternary ammonium salt pyranine compound is obtained by reacting 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt;
the organosilicon quaternary ammonium salt has a structure shown in a formula (I):
wherein R is1And R2Each independently selected from-CH3、-CH2CH3；
R3Is selected from alkyl of C6-C18.
2. The antibacterial coating layer with a pH monitoring function according to claim 1, wherein the coating layer has a structure in which a trisodium salt of 8-hydroxy-1, 3, 6-pyrenetrisulfonate and a quaternary ammonium salt of silicone are cross-linked with each other;
the coating is bonded with the coated substrate through chemical bonds;
the thickness of the coating is 0.001-100 mu m.
3. The antibacterial coating layer with a pH monitoring function according to claim 2, wherein in the coating layer, the trisodium 8-hydroxy-1, 3, 6-pyrenetrisulfonate and quaternary ammonium silicone salt have a Si-O cross-linked structure;
the chemical bond is a Si-O bond;
the molar ratio of the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt to the organosilicon quaternary ammonium salt in the organosilicon quaternary ammonium salt pyranine compound is 1: (1-4);
the coated substrate is a surface hydroxylated coated substrate;
the surface of the coated substrate is crosslinked with the coating layer through interweaving points.
4. The antibacterial coating with pH monitoring function according to claim 1, wherein the reaction of the trisodium 8-hydroxy-1, 3, 6-pyrenetrisulfonate and the organosilicon quaternary ammonium salt specifically results in:
mixing the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and the organosilicon quaternary ammonium salt to obtain an organosilicon quaternary ammonium salt/pyranine compound, and reacting to obtain the compound;
the organosilicon quaternary ammonium salt/pyranine compound is an electrostatic self-assembly compound;
the reaction is a thermal curing reaction;
the temperature of the thermosetting reaction is 50-140 ℃;
the time of the thermosetting reaction is 0.1-12 h.
5. The functional material of the antibacterial coating with the pH monitoring function is characterized by comprising a base material and the antibacterial coating with the pH monitoring function, which is compounded on the base material;
the antibacterial coating with the pH monitoring function comprises the antibacterial coating with the pH monitoring function of any one of claims 1 to 4.
6. The functional material of claim 5, wherein the matrix material comprises one or more of polyethylene, polypropylene, polyvinyl chloride, polycarbonate, polyurethane, polystyrene, polyamide, polyether block polyamide, polytetrafluoroethylene, fluorinated ethylene-propylene copolymer, polymethyl methacrylate, thermoplastic elastomer, latex, and silicone rubber;
the matrix material comprises a medical material.
7. A preparation method of a functional material of an antibacterial coating with a pH monitoring function is characterized by comprising the following steps:
1) mixing 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt solution with a structure shown in a formula (I) to obtain organosilicon quaternary ammonium salt/pyranine compound solution;
wherein R is1And R2Each independently selected from-CH3、-CH2CH3；
R3Alkyl selected from C6-C18;
2) and compounding the organosilicon quaternary ammonium salt/pyranine compound solution obtained in the step on the surface of the material subjected to surface hydroxylation, and performing thermocuring to obtain the functional material of the antibacterial coating with the pH monitoring function.
8. The preparation method according to claim 7, wherein the concentration of the solution of the silicone quaternary ammonium salt is 0.01 to 15 g/mL;
the mass concentration of the organosilicon quaternary ammonium salt/pyranine compound solution is 0.01-20 g/mL;
the organosilicon quaternary ammonium salt solution comprises an organosilicon quaternary ammonium salt alcohol solution;
the 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt comprises 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt powder or 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt alcoholic solution;
the concentration of the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt solution is 0.01-5 g/mL.
9. The method of claim 8, wherein the alcohol comprises one or more of methanol, ethanol, propanol, isopropanol, n-butanol, and benzyl alcohol;
the surface hydroxylation step comprises the following steps:
carrying out plasma treatment on the material to obtain a material with a hydroxylated surface;
the material comprises a medical material;
the mol ratio of the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt to the organosilicon quaternary ammonium salt in the compound is 1: (1-4);
the temperature of the thermosetting is 50-140 ℃;
the thermosetting time is 0.1-12 h.
10. The method of manufacturing of claim 9, wherein the medical material comprises a medical catheter;
the gas in the plasma treatment process comprises one or more of air, oxygen, argon and nitrogen;
the flow rate of the gas is 2-500 cc/min;
the power of the plasma treatment is 20-800W;
the pressure of the plasma treatment is 5-100 Pa;
the plasma treatment time is 1-30 min.
Technical Field
The invention belongs to the field of antibacterial medical instruments, and relates to an antibacterial coating with a pH monitoring function, a functional material of the antibacterial coating with the pH monitoring function and a preparation method of the functional material, in particular to an antibacterial coating with the pH monitoring function, a medical material of the antibacterial coating with the pH monitoring function and a preparation method of the medical material.
Background
Nosocomial infections not only cause significant increase in patient morbidity and mortality, but also cause significant economic losses to patients and society, posing serious challenges to the global health care industry. According to statistics, the additional fatality rate caused by hospital infection is 4-33%. Nosocomial infections occur in about 72 million people per year in the united states, resulting in about 7.5 million deaths, adding to the cost of medical care by about $ 45 to $ 110. Therefore, the prevention and treatment of medical appliance related infection is greatly urgent.
Adhesion, proliferation and biofilm formation of bacteria on the surface of biomedical materials are the main causes of contamination of medical devices and infection related to medical devices. Patients need to undergo various diagnostic and therapeutic measures during hospitalization, such as tracheal intubation, urinary tract intubation, surgical treatment, etc., which provides conditions for microorganisms to enter the patient through various contaminated instruments and cause infections.
Imparting antimicrobial properties to the surface of materials is an effective way to combat bacterial infections. Although the working efficiency of the existing antibacterial system is continuously improved and the use scenes are continuously enriched, the research range mainly focuses on the optimization of the antibacterial function of the material, and the efficient interaction of the material and people cannot be realized. The main performance is as follows: the material itself does not have the ability to convey information such as bacterial contamination sites, contamination levels, etc., and people cannot make a real-time judgment on the current antibacterial state of the material and take corresponding subsequent treatment measures (e.g., supplement of antibacterial agents, replacement of antibacterial mechanisms, etc.).
In order to obtain such information, people often need to additionally perform a series of independent and complicated bacteria monitoring operations: such as ultrasonic separation sampling, bacterial colony culture, surface staining treatment and the like. The conventional operation of separately processing the material using, sampling and monitoring usually has a certain time lag, and the working state of the material in clinical application cannot be reflected in real time, thereby causing delay of treatment. For a purely bacteria-monitoring surface, even if convenient information transmission can be achieved, the absence of the antibacterial function can still cause infection of medical equipment, or the material itself cannot control the development of infection at the first time.
Therefore, how to design a material, which can integrate two separate functions (processes) of bacteria monitoring and antibacterial, and construct an integrated material surface, to solve the above-mentioned defects, so as to realize prevention, diagnosis, control and treatment of medical device-related infection has become one of the focuses of the prospective researchers in the field.
Disclosure of Invention
In view of the above, the technical problems to be solved by the present invention are an antibacterial coating with pH monitoring function, a functional material of the antibacterial coating with pH monitoring function and a preparation method thereof, and particularly an antibacterial coating with pH monitoring function. The antibacterial coating provided by the invention comprises the organosilicon quaternary ammonium salt pyranine compound, has pH dependency, generates different fluorescence effects under different pH conditions, and can realize monitoring on the bacterial infection degree and the infected part; the quaternary ammonium salt component in the coating has a bactericidal effect and can inhibit the development and deterioration of bacterial infection.
The invention provides an antibacterial coating with a pH monitoring function, which comprises an organosilicon quaternary ammonium salt pyranine compound;
the organosilicon quaternary ammonium salt pyranine compound is obtained by reacting 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt;
the organosilicon quaternary ammonium salt has a structure shown in a formula (I):
wherein R is1And R2Each independently selected from-CH3、-CH2CH3；
R3Is selected from alkyl of C6-C18.
Preferably, the coating has a structure that 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt are mutually crosslinked;
the coating is bonded with the coated substrate through chemical bonds;
the thickness of the coating is 0.001-100 mu m.
Preferably, in the coating, the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and the organosilicon quaternary ammonium salt have a Si-O crosslinking structure;
the chemical bond is a Si-O bond;
the molar ratio of the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt to the organosilicon quaternary ammonium salt in the organosilicon quaternary ammonium salt pyranine compound is 1: (1-4);
the coated substrate is a surface hydroxylated coated substrate;
the surface of the coated substrate is crosslinked with the coating layer through interweaving points.
Preferably, the reaction between the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and the organosilicon quaternary ammonium salt is as follows:
mixing the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and the organosilicon quaternary ammonium salt to obtain an organosilicon quaternary ammonium salt/pyranine compound, and reacting to obtain the compound;
the organosilicon quaternary ammonium salt/pyranine compound is an electrostatic self-assembly compound;
the reaction is a thermal curing reaction;
the temperature of the thermosetting reaction is 50-140 ℃;
the time of the thermosetting reaction is 0.1-12 h.
The invention provides a functional material of an antibacterial coating with a pH monitoring function, which comprises a base material and the antibacterial coating with the pH monitoring function, wherein the antibacterial coating is compounded on the base material;
the antibacterial coating with the pH monitoring function comprises the antibacterial coating with the pH monitoring function in any one of the technical schemes.
Preferably, the material of the base material comprises one or more of polyethylene, polypropylene, polyvinyl chloride, polycarbonate, polyurethane, polystyrene, polyamide, polyether block polyamide, polytetrafluoroethylene, fluorinated ethylene-propylene copolymer, polymethyl methacrylate, thermoplastic elastomer, latex and silicon rubber;
the matrix material comprises a medical material.
The invention provides a preparation method of a functional material of an antibacterial coating with a pH monitoring function, which is characterized by comprising the following steps:
1) mixing 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt solution with a structure shown in a formula (I) to obtain organosilicon quaternary ammonium salt/pyranine compound solution;
wherein R is1And R2Each independently selected from-CH3、-CH2CH3；
R3Alkyl selected from C6-C18;
2) and compounding the organosilicon quaternary ammonium salt/pyranine compound solution obtained in the step on the surface of the material subjected to surface hydroxylation, and performing thermocuring to obtain the functional material of the antibacterial coating with the pH monitoring function.
Preferably, the concentration of the organosilicon quaternary ammonium salt solution is 0.01-15 g/mL;
the mass concentration of the organosilicon quaternary ammonium salt/pyranine compound solution is 0.01-20 g/mL;
the organosilicon quaternary ammonium salt solution comprises an organosilicon quaternary ammonium salt alcohol solution;
the 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt comprises 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt powder or 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt alcoholic solution;
the concentration of the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt solution is 0.01-5 g/mL.
Preferably, the alcohol comprises one or more of methanol, ethanol, propanol, isopropanol, n-butanol and benzyl alcohol;
the surface hydroxylation step comprises the following steps:
carrying out plasma treatment on the material to obtain a material with a hydroxylated surface;
the material comprises a medical material;
the mol ratio of the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt to the organosilicon quaternary ammonium salt in the compound is 1: (1-4);
the temperature of the thermosetting is 50-140 ℃;
the thermosetting time is 0.1-12 h.
Preferably, the medical material comprises a medical catheter;
the gas in the plasma treatment process comprises one or more of air, oxygen, argon and nitrogen;
the flow rate of the gas is 2-500 cc/min;
the power of the plasma treatment is 20-800W;
the pressure of the plasma treatment is 5-100 Pa;
the plasma treatment time is 1-30 min.
The invention provides an antibacterial coating with a pH monitoring function, which comprises an organosilicon quaternary ammonium salt pyranine compound; the organosilicon quaternary ammonium salt pyranine compound is obtained by reacting 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt; the organosilicon quaternary ammonium salt has a structure shown in a formula (I). Compared with the prior art, the invention aims at the problems that the existing coating does not have the capacity of transmitting information such as bacterial contamination sites, contamination degrees and the like, cannot judge the current antibacterial state of the material in real time and take corresponding subsequent treatment measures, needs to additionally carry out a series of independent and complex bacteria monitoring operations, has certain time lag, and cannot reflect the working state of the material in clinical application in real time, thereby causing treatment delay. Even if convenient information transmission can be realized, the lack of the antibacterial function still causes the infection of medical instruments or the material can not control the development of the infection at the first time. And although the coating has certain stability, the coating and the substrate still have the problems of weak bonding strength, large environmental influence and large risk of local or overall falling of the coating.
According to the invention, the research is carried out based on the mechanism direction, when bacteria breed on the surface of the material, the change of the pH value of the microenvironment on the surface of the material can be caused by the generation of enzymes and metabolites (such as lactic acid, acetic acid and the like), and the condition is provided for monitoring bacterial infection. The antibacterial coating with the pH monitoring function has pH dependence, generates different fluorescence effects under different pH conditions, and can monitor the bacterial infection degree and the infected part; and the quaternary ammonium salt component in the coating has a bactericidal effect, and can inhibit the development and deterioration of bacterial infection. In addition, the releaseability of the existing coating is not changed substantially, and the interaction mode between the coating and the substrate material is still physical action, so that the coating still has the problems of weak bonding strength with the substrate material, large environmental influence and large risk of local or overall falling off of the coating. The existing method for coating the hydrogen abstraction quaternary ammonium salt compound still has the defects of potential biotoxicity, no commercial product and high cost of the hydrogen abstraction quaternary ammonium salt molecule, and simultaneously has the problem that the method for directly curing the hydrogen abstraction quaternary ammonium salt by ultraviolet light is difficult to operate in response to interventional medical instruments with complex structures and non-transparent materials.
The invention creatively reacts 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt with organosilicon quaternary ammonium salt with a structure shown in a formula (I) to obtain the organosilicon quaternary ammonium salt pyranine compound coating. Siloxane groups in the organic silicon quaternary ammonium salt can respectively generate silanization reaction with 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt molecules and the surface of a hydroxylated base material, not only pyranine and the organic silicon quaternary ammonium salt in the coating are mutually crosslinked, the stability of the coating is improved, but also the coating is bonded with the coated base through chemical bonds, and compared with common chemical bond bonding, a single organic silicon quaternary ammonium salt molecule can be used as the same crosslinking point to realize different Si-O bonds on a single molecule, the coating is crosslinked with the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt molecules, and is also bonded with the coated base through chemical bonds, and the chemical bond crosslinking mode of the crosslinking point greatly improves the stability of the coating and the coated base so that the coating is more firmly fixed on the surface of the material, thereby avoiding the dissociation and falling off of the coating of the medical catheter in the process of intervention and retention, and having more lasting pH detection and antibacterial effect.
The antibacterial coating with the pH monitoring function provided by the invention can be formed in a heating and curing mode in the preparation process, the equipment requirement is low, the process is simpler, the operation is easy, the feasibility is high, and the problem that the traditional heat curing method is difficult to operate when the traditional heat curing method is used for interventional medical equipment with a complex structure and non-transparent materials is solved. And the coating has wide applicability, and is even suitable for interventional medical instruments with complex structures and non-transparent materials.
Experimental results show that the antibacterial coating with the pH monitoring function can achieve the highest 100% sterilization rate on staphylococcus aureus and escherichia coli, and bacteria are in a damaged form of shrivelled, cracked and ablated bacterial membrane after contacting the coating; in an acidic culture solution triggered by bacteria, the coating presents different fluorescent colors along with the change of pH, and shows the functions of bacterial infection indication and early warning.
Drawings
FIG. 1 is a photograph showing the appearance of bacteria on the surface of a sample treated with the pH monitoring antibacterial coating obtained in example 1;
FIG. 2 is a photograph of the topography of bacteria on the surface of an uncoated treated sample;
FIG. 3 is a photograph of a bacterial plate on the surface of a sample treated with the antibacterial coating having pH monitoring function obtained in example 1;
FIG. 4 is a photograph of a bacterial plating of the uncoated treated sample surface.
Detailed Description
For a further understanding of the invention, reference will now be made to the preferred embodiments of the invention by way of example, and it is to be understood that the description is intended to further illustrate features and advantages of the invention, and not to limit the scope of the claims.
The material used in the present invention, the source of which is not particularly limited, may be purchased commercially or prepared according to a conventional method well known to those skilled in the art.
All of the raw materials of the present invention are not particularly limited in terms of purity or standard, and the present invention is preferably of a purity level that is conventional in the medical device field or medical grade.
In the present invention, a person skilled in the art can correctly understand that the meanings represented by the two expressions (×) and (×) are equivalent, and the presence or absence of parentheses does not affect the actual meanings thereof.
In the present specification, "-substituent" in the structural formula means that the substituent may be at any position of the group.
All compounds of the present invention, whose structural expressions and abbreviations belong to the common structural expressions and abbreviations in the art, are clearly and unambiguously understood in the field of their related uses, and those skilled in the art can clearly, exactly and uniquely understand them according to the structural expressions and abbreviations.
The invention provides an antibacterial coating with a pH monitoring function, which is characterized by comprising an organosilicon quaternary ammonium salt pyranine compound;
the organosilicon quaternary ammonium salt pyranine compound is obtained by reacting 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt;
the organosilicon quaternary ammonium salt has a structure shown in a formula (I):
wherein R is1And R2Each independently selected from-CH3、-CH2CH3；
R3Is selected from alkyl of C6-C18.
In the present invention, R1And R2Each independently selected from-CH3、-CH2CH3More preferably R1Preferably selected from-CH3and/or-CH2CH3，R2Preferably selected from-CH3and/or-CH2CH3。R3Is selected from C6-C18 alkyl, more preferably C8-C16 alkyl, more preferably C10-C14 alkyl, and the specific number of C can be 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18.
In the invention, the antibacterial coating with the pH monitoring function comprises an organosilicon quaternary ammonium salt pyranine compound. The specific definition of the organosilicon quaternary ammonium salt pyranine compounds, i.e. the compounds obtained after the 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt and the organosilicon quaternary ammonium salt are bonded by chemical bonds, is not particularly limited in the present invention, as is the conventional definition of such compounds well known to the person skilled in the art, which may be selected and adjusted by the person skilled in the art according to the actual circumstances, performance requirements and product requirements.
The specific structure of the coating is not particularly limited in principle, and can be selected and adjusted by a person skilled in the art according to actual conditions, performance requirements and product requirements, and the coating preferably has a structure in which 8-hydroxy-1, 3, 6-pyrene trisulfonate trisodium salt and organosilicon quaternary ammonium salt are cross-linked with each other, and more preferably has a Si-O cross-linked structure, so as to better ensure the cross-linked structure in the coating, improve the connection performance of the coating and a coated substrate, and further improve the pH monitoring and antibacterial effects of the coating. Namely, the mutual crosslinking of Si-O bonds is realized between the 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt molecules and/or the 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt molecules through organosilicon quaternary ammonium salt.
The invention has no special limitation on the parameters of the coating in principle, and a person skilled in the art can select and adjust the parameters according to actual conditions, performance requirements and product requirements, in order to better ensure the cross-linking structure in the coating, improve the connection performance of the coating and a coated substrate and further improve the pH monitoring and antibacterial effects of the coating, the thickness of the coating is preferably 0.001-100 μm, more preferably 0.01-10 μm, more preferably 0.1-1 μm, and more preferably 0.3-0.8 μm.
The invention has no special restriction on the connection relation of the coating and the coated substrate in principle, and the skilled person can select and adjust the connection relation according to the actual situation, the performance requirement and the product requirement.
The invention is not particularly limited to the specific structure of the coated substrate in principle, and can be selected and adjusted by a person skilled in the art according to the actual situation, performance requirements and product requirements, in order to better ensure the cross-linked structure in the coating, improve the connection performance of the coating and the coated substrate, and further improve the pH monitoring and antibacterial effects of the coating, the coated substrate is preferably a surface-hydroxylated coated substrate, and more preferably a plasma-treated surface-hydroxylated coated substrate.
The invention has no special limitation on the parameters of the organosilicon quaternary ammonium salt pyranine compound in principle, and the person skilled in the art can select and adjust the parameters according to the actual situation, the performance requirement and the product requirement, in order to better ensure the cross-linking structure in the coating, improve the connection performance of the coating and the coated substrate and further improve the pH monitoring and antibacterial effect of the coating, the molar ratio of the 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt to the organosilicon quaternary ammonium salt in the organosilicon quaternary ammonium salt pyranine compound is preferably 1: (1 to 4), more preferably 1: (1.5 to 3.5), more preferably 1: (2-3).
The organosilicon quaternary ammonium salt pyranine compound is obtained by reacting 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt.
The 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt is preferably of a structure shown in a formula (II). The formula (II) is a schematic structural formula of the structure of the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt.
The organosilicon quaternary ammonium salt has a structure shown in a formula (I). The invention has no special limitation on the specific selection of the corresponding anions in the organosilicon quaternary ammonium salt raw material in principle, and the skilled person in the art can select and adjust the anions according to the actual situation, the performance requirement and the product requirementAnd further improve the pH monitoring and antibacterial effects of the coating, the corresponding anions in the organosilicon quaternary ammonium salt raw material preferably comprise halogen anions, and more preferably Cl-、Br-And I-More preferably Cl-、Br-Or I-。
The specific parameters of the reaction are not particularly limited in principle, and can be selected and adjusted by a person skilled in the art according to actual conditions, performance requirements and product requirements. The reaction temperature is preferably 50-140 ℃, more preferably 60-120 ℃, and more preferably 70-100 ℃. The reaction time is preferably 0.1-12 h, more preferably 0.5-10 h, more preferably 1-8 h, and more preferably 2-6 h.
The invention is a complete and detailed technical scheme, better ensures the cross-linking structure in the coating, improves the connection performance of the coating and the coated substrate, and further improves the pH monitoring and antibacterial effects of the coating, and the specific steps of the reaction are preferably as follows:
the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and the organosilicon quaternary ammonium salt are mixed to obtain an organosilicon quaternary ammonium salt/pyranine compound, and then the compound is obtained after reaction.
The specific definition of the organic silicon quaternary ammonium salt/pyranine compound is not particularly limited in principle, and the organic silicon quaternary ammonium salt/pyranine compound is defined by the conventional definition of the substances well known to those skilled in the art, and is preferably an electrostatic self-assembly compound, so that the cross-linked structure in the coating is better ensured, the connection performance of the coating and a coated substrate is improved, and the pH monitoring and antibacterial effects of the coating are further improved. In the present invention, -SO in the trisodium salt of 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid3-the presence of a substantial negative charge on the pyranine molecule in aqueous (or alcoholic) solution and a positive charge on the silicone quaternary ammonium salt, which upon mixing in solution, electrostatically interact and form a silicone quaternary ammonium salt/pyranine complex.
In the invention, three siloxane groups of the organosilicon quaternary ammonium salt can perform silanization reaction with hydroxyl to form new chemical bonds. The self-crosslinking of the coating is realized by reacting with the hydroxyl of the trisodium 8-hydroxy-1, 3, 6-pyrenetrisulfonate molecule, and the current situation of the stability of the coating is improved; and the coating is fixed on the surface of the catheter in a chemical bond form by reacting with hydroxyl on the surface of the material after plasma treatment (after hydroxylation), so that the adhesion of the coating is improved. In addition, in the chemical bonding mode, Si atoms in a single organosilicon quaternary ammonium salt molecule can be used as the same cross-linking point to realize different Si-O bonds on a single molecule, the different Si-O bonds are not only cross-linked with hydroxyl groups in 8-hydroxyl-1, 3, 6-pyrenetrisulfonic acid trisodium salt molecules, but also are chemically bonded with a coated substrate, and the cross-linking point is in a chemical bonding cross-linking mode rather than a simple mode of carrying out chemical bonding surface cross-linking on a single substituent on a certain molecule in a coating. The point crosslinking in the invention can also be understood as monoatomic crosslinking, in which chemical bonds on a monoatomic atom are crosslinked with different molecules, but different atoms on a single molecule are crosslinked with other molecules on a molecular level.
The coating structure provided by the invention greatly improves the stability of the coating and the coated substrate, so that the coating is more firmly fixed on the surface of the material, the dissociation and falling off of the coating in the intervention, use (such as liquid medicine, blood flow flushing and the like) and indwelling processes of medical equipment are avoided, and the pH monitoring and antibacterial effects are more durable.
The invention provides a functional material of an antibacterial coating with a pH monitoring function, which comprises a base material and the antibacterial coating with the pH monitoring function, wherein the antibacterial coating is compounded on the base material;
the antibacterial coating with the pH monitoring function comprises the antibacterial coating with the pH monitoring function in any one of the technical schemes.
The structure, the material and the specific parameters of the antibacterial coating with the pH monitoring function in the functional material and the corresponding preferred principle of the invention preferably correspond to the structure, the material and the specific parameters of the antibacterial coating with the pH monitoring function and the corresponding preferred principle, and are not described in detail herein.
The specific selection of the matrix material is not particularly limited in principle, and can be selected and adjusted by a person skilled in the art according to actual conditions, performance requirements and product requirements. The material of the matrix material of the invention preferably comprises one or more of polyethylene, polypropylene, polyvinyl chloride, polycarbonate, polyurethane, polystyrene, polyamide, polyether block polyamide, polytetrafluoroethylene, fluorinated ethylene-propylene copolymer, polymethyl methacrylate, thermoplastic elastomer, latex and silicone rubber, and more preferably polyethylene, polypropylene, polyvinyl chloride, polycarbonate, polyurethane, polystyrene, polyamide, polyether block polyamide, polytetrafluoroethylene, fluorinated ethylene-propylene copolymer, polymethyl methacrylate, thermoplastic elastomer, latex or silicone rubber.
The invention also provides a preparation method of the antibacterial coating with the pH monitoring function, which comprises the following steps:
1) mixing pyranine sodium and an organosilicon quaternary ammonium salt solution with a structure shown in a formula (I) to obtain an organosilicon quaternary ammonium salt/pyranine compound solution;
wherein R is1And R2Each independently selected from-CH3、-CH2CH3；
R3Alkyl selected from C6-C18;
2) and (3) carrying out thermocuring on the organosilicon quaternary ammonium salt/pyranine compound solution obtained in the step to obtain the antibacterial coating with the pH monitoring function.
The structure, material and specific parameters of the compound, specific process parameters, and corresponding preferred principles in the preparation method of the present invention may preferably correspond to the structure, material and specific parameters of the compound, specific process parameters, and corresponding preferred principles in the functional material of the antibacterial coating with pH monitoring function in the following, and are not described in detail herein, and the following may be referred to.
The invention also provides a preparation method of the functional material of the antibacterial coating with the pH monitoring function, which comprises the following steps:
1) mixing 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt solution with a structure shown in a formula (I) to obtain organosilicon quaternary ammonium salt/pyranine compound solution;
wherein R is1And R2Each independently selected from-CH3、-CH2CH3；
R3Alkyl selected from C6-C18;
2) and compounding the organosilicon quaternary ammonium salt/pyranine compound solution obtained in the step on the surface of the material subjected to surface hydroxylation, and performing thermocuring to obtain the functional material of the antibacterial coating with the pH monitoring function.
The structure, material and specific parameters of the compound involved in the preparation method of the functional material, and the corresponding preferred principle, of the present invention, may preferably correspond to the structure, material and specific parameters of the compound in the antibacterial coating layer with the pH monitoring function, and the corresponding preferred principle, and are not described in detail herein.
The preparation method comprises the steps of mixing 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt and organosilicon quaternary ammonium salt solution with a structure shown in a formula (I) to obtain organosilicon quaternary ammonium salt/pyranine compound solution.
The specific parameters of the organic silicon quaternary ammonium salt solution are not particularly limited in principle, and a person skilled in the art can select and adjust the specific parameters according to actual conditions, performance requirements and product requirements, in order to better ensure the cross-linking structure inside the coating, improve the connection performance of the coating and a coated substrate and further improve the pH monitoring and antibacterial effects of the coating, the concentration of the organic silicon quaternary ammonium salt solution is preferably 0.01-15 g/mL, more preferably 0.05-10 g/mL, more preferably 0.1-5 g/mL, more preferably 0.5-1 g/mL, and more preferably 0.6-0.9 g/mL.
The specific selection of the organosilicon quaternary ammonium salt solution is not particularly limited in principle, and can be selected and adjusted by a person skilled in the art according to actual conditions, performance requirements and product requirements. More specifically, the alcohol preferably includes one or more of methanol, ethanol, propanol, isopropanol, n-butanol, and benzyl alcohol, and more preferably methanol, ethanol, propanol, isopropanol, or benzyl alcohol.
The specific selection and parameters of the trisodium 8-hydroxy-1, 3, 6-pyrenetrisulfonate are not particularly limited in principle, and can be selected and adjusted by those skilled in the art according to actual conditions, performance requirements and product requirements, and the trisodium 8-hydroxy-1, 3, 6-pyrenetrisulfonate preferably comprises trisodium 8-hydroxy-1, 3, 6-pyrenetrisulfonate powder or trisodium 8-hydroxy-1, 3, 6-pyrenetrisulfonate alcoholic solution in order to better ensure the cross-linked structure in the coating, improve the connection performance of the coating and the coated substrate and further improve the pH monitoring and antibacterial effects of the coating. More specifically, the alcohol preferably includes one or more of methanol, ethanol, propanol, isopropanol, n-butanol, and benzyl alcohol, and more preferably methanol, ethanol, propanol, isopropanol, or benzyl alcohol. The concentration of the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt solution is preferably 0.01-5 g/mL, more preferably 0.05-1 g/mL, and more preferably 0.1-0.5 g/mL.
The addition proportion of the 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt is not particularly limited in principle, and can be selected and adjusted by a person skilled in the art according to actual conditions, performance requirements and product requirements, the invention is used for better ensuring a cross-linked structure in a coating, improving the connection performance of the coating and a coated substrate and further improving the pH monitoring and antibacterial effects of the coating, and the mass concentration of the organosilicon quaternary ammonium salt/pyranine compound solution is preferably 0.01-20 g/mL, more preferably 0.1-10 g/mL, more preferably 0.5-1 g/mL, and more preferably 0.6-0.9 g/mL.
The specific parameters of the organosilicon quaternary ammonium salt/pyranine compound are not particularly limited in principle, and can be selected and adjusted by a person skilled in the art according to actual conditions, performance requirements and product requirements, in order to better ensure the cross-linking structure in the coating, improve the connection performance of the coating and a coated substrate and further improve the pH monitoring and antibacterial effects of the coating, the molar ratio of the 8-hydroxy-1, 3, 6-pyrene trisulfonic acid trisodium salt to the organosilicon quaternary ammonium salt in the organosilicon quaternary ammonium salt/pyranine compound is preferably 1: (1 to 4), more preferably 1: (1.5 to 3.5), more preferably 1: (2-3).
According to the invention, the organosilicon quaternary ammonium salt/pyranine compound solution obtained in the above steps is compounded on the surface of the material after surface hydroxylation, and the functional material of the antibacterial coating with the pH monitoring function is obtained after thermocuring.
The invention is not particularly limited in principle to the compounding manner, and can be selected and adjusted by those skilled in the art according to actual conditions, performance requirements and product requirements, and the invention is to better ensure the cross-linked structure inside the coating, improve the connection performance of the coating and the coated substrate, and further improve the pH monitoring and antibacterial effects of the coating, and the compounding is preferably carried, and more particularly preferably comprises one or more of dipping, dip coating, spraying, spray coating, spin coating and wiping.
The specific parameters of the thermosetting are not particularly limited in principle, and a person skilled in the art can select and adjust the specific parameters according to actual conditions, performance requirements and product requirements, the temperature of the thermosetting is preferably 50-140 ℃, more preferably 60-120 ℃, and more preferably 70-100 ℃, in order to better ensure the cross-linking structure in the coating, improve the connection performance of the coating and the coated substrate and further improve the pH monitoring and antibacterial effects of the coating. The time for the heat curing is preferably 0.1-12 hours, more preferably 0.5-10 hours, more preferably 1-8 hours, and more preferably 2-6 hours.
The invention has no particular limitation on the specific steps and parameters of the surface hydroxylation in principle, and a person skilled in the art can select and adjust the steps according to the actual conditions, the performance requirements and the product requirements, in order to better ensure the cross-linking structure in the coating, improve the connection performance of the coating and the coated substrate and further improve the pH monitoring and antibacterial effects of the coating, the steps of the surface hydroxylation are preferably as follows:
and carrying out plasma treatment on the material to obtain the material with the hydroxylated surface.
The material is not particularly limited in principle, and can be selected and adjusted by those skilled in the art according to actual conditions, performance requirements and product requirements, and the material of the material preferably comprises one or more of polyethylene, polypropylene, polyvinyl chloride, polycarbonate, polyurethane, polystyrene, polyamide, polyether block polyamide, polytetrafluoroethylene, fluorinated ethylene-propylene copolymer, polymethyl methacrylate, thermoplastic elastomer, latex and silicone rubber, so as to better ensure the cross-linked structure inside the coating, improve the connection performance of the coating and the coated substrate and further improve the pH monitoring and antibacterial effects of the coating. The material preferably comprises a medical material, more preferably a medical catheter.
The material is not particularly limited in principle, and can be selected and adjusted by a person skilled in the art according to actual conditions, performance requirements and product requirements. The flow rate of the gas is preferably 2 to 500cc/min, more preferably 20 to 400cc/min, more preferably 100 to 300cc/min, and more preferably 150 to 250 cc/min. The power of the plasma treatment is preferably 20-800W, more preferably 120-600W, more preferably 220-500W, more preferably 320-400W. The pressure of the plasma treatment is preferably 5 to 100Pa, more preferably 25 to 80Pa, and still more preferably 45 to 60 Pa. The plasma treatment time is preferably 1 to 30min, more preferably 5 to 25min, and still more preferably 10 to 20 min.
Referring to fig. 1, fig. 1 is a schematic view illustrating a cross-linked structure inside an antibacterial coating having a pH monitoring function and a connection with a substrate in a functional material of the antibacterial coating having a pH monitoring function according to the present invention.
The invention is a complete and refined integral preparation process, better ensures the cross-linking structure in the coating, improves the connection performance of the coating and the coated substrate, and further improves the pH monitoring and antibacterial effects of the coating, and the preparation method of the functional material of the antibacterial coating with the pH monitoring function can specifically comprise the following steps:
A) carrying out plasma treatment on the medical catheter to obtain a medical catheter surface with hydroxylated surface;
B) mixing the organosilicon quaternary ammonium salt solution with the structure of formula (I) and 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt solution, centrifuging and drying to obtain an organosilicon quaternary ammonium salt/pyranine compound;
C) dissolving the organic silicon quaternary ammonium salt/pyranine compound in an organic solvent, and loading the organic silicon quaternary ammonium salt/pyranine compound on the surface of the medical catheter in a dipping, spraying, spin coating or wiping mode;
D) and drying the organic silicon quaternary ammonium salt/pyranine-loaded compound, and then thermally curing to finally obtain the antibacterial medical catheter with the pH monitoring function.
The invention provides the antibacterial coating with the pH monitoring function and the preparation method thereof, and the medical material of the antibacterial coating with the pH monitoring function and the preparation method thereof. The invention obtains the organosilicon quaternary ammonium salt pyranine compound coating by reacting 8-hydroxy-1, 3, 6-pyrenetrisulfonic acid trisodium salt with organosilicon quaternary ammonium salt with a structure of a formula (I). Three siloxane groups of the organosilicon quaternary ammonium salt can perform silanization reaction with hydroxyl groups to form new chemical bonds. The self-crosslinking of the coating is realized by reacting with the hydroxyl of the trisodium 8-hydroxy-1, 3, 6-pyrenetrisulfonate molecule, and the current situation of the stability of the coating is improved; and the coating is fixed on the surface of the catheter in a chemical bond form by reacting with hydroxyl on the surface of the material after plasma treatment (after hydroxylation), so that the adhesion of the coating is improved. In addition, in the chemical bonding mode, Si atoms in a single organosilicon quaternary ammonium salt molecule can be used as the same cross-linking point to realize different Si-O bonds on a single molecule, the different Si-O bonds are not only cross-linked with hydroxyl groups in 8-hydroxyl-1, 3, 6-pyrenetrisulfonic acid trisodium salt molecules, but also are chemically bonded with a coated substrate, and the cross-linking point is in a chemical bonding cross-linking mode rather than a simple mode of carrying out chemical bonding surface cross-linking on a single substituent on a certain molecule in a coating. The point crosslinking in the invention can also be understood as monoatomic crosslinking, in which chemical bonds on a monoatomic atom are crosslinked with different molecules, but different atoms on a single molecule are crosslinked with other molecules on a molecular level.
The coating structure provided by the invention greatly improves the stability of the coating and the coated substrate, so that the coating is more firmly fixed on the surface of the material, the dissociation and the falling off of the coating in the process of intervention, use (such as liquid medicine, blood flow scouring and the like) and indwelling process of medical devices such as medical catheters and the like are avoided, and the pH monitoring and antibacterial effects are more durable.
The antibacterial coating with the pH monitoring function provided by the invention can be formed in a heating and curing manner in the preparation process, the process is simpler, the operation is easy, the feasibility is high, and the problem that the traditional heat curing method is difficult to operate when the traditional heat curing method is used for interventional medical equipment with a complex structure is solved.
Experimental results show that the antibacterial coating with the pH monitoring function can achieve the highest 100% sterilization rate on staphylococcus aureus and escherichia coli, and bacteria are in a damaged form of shrivelled, cracked and ablated bacterial membrane after contacting the coating; in an acidic culture solution triggered by bacteria, the coating presents different fluorescent colors along with the change of pH, and shows the functions of bacterial infection indication and early warning.
For further illustration of the present invention, the following will describe in detail an antibacterial coating with pH monitoring function, a functional material of an antibacterial coating with pH monitoring function and a preparation method thereof provided by the present invention with reference to the following examples, but it should be understood that these examples are implemented on the premise of the technical solution of the present invention, and the detailed embodiments and specific operation procedures are given only for further illustration of the features and advantages of the present invention, and not for limitation of the claims of the present invention, and the scope of protection of the present invention is not limited to the following examples.