阅读说明：本技术 非释放型抗微生物黏附涂层在抗菌医疗器械中的应用 (Use of non-releasing antimicrobial adhesive coatings in antimicrobial medical devices ) 是由 王兴 于 2020-06-17 设计创作，主要内容包括：本发明涉及一种非释放型抗微生物黏附涂层在抗菌医疗器械中的应用,该涂层的主要成分由丙烯酸龙脑酯(BA)和聚乙二醇二丙烯酸酯(PEGDA)两种单体的共聚物构成,构建两亲立体化学抗菌高分子涂层,该涂层具有良好的抗微生物黏附性。该涂层制备方法主要包括以下步骤：第一步将光引发剂固定在医疗器械表面,第二步将单体通过表面自由基引发聚合实现接枝以及共聚。本发明中所述涂层的制备方法简单,所得的接枝涂层安全稳定；可以充分发挥聚丙烯酸龙脑酯和聚乙二醇二丙烯酸酯各自的优点,协同阻止微生物粘附；该涂层可以应用于医疗器械表面的改性,能够确保接枝涂层的结构平整。(The invention relates to an application of a non-release antimicrobial adhesive coating in an antibacterial medical appliance, wherein the main component of the coating is formed by a copolymer of two monomers, namely, Borneol Acrylate (BA) and polyethylene glycol diacrylate (PEGDA), an amphiphilic stereochemical antibacterial high polymer coating is constructed, and the coating has good antimicrobial adhesion. The preparation method of the coating mainly comprises the following steps: in the first step, a photoinitiator is fixed on the surface of the medical appliance, and in the second step, the monomer is grafted and copolymerized through surface free radical initiated polymerization. The preparation method of the coating is simple, and the obtained grafted coating is safe and stable; the respective advantages of the polyacrylic borneol ester and the polyethylene glycol diacrylate can be fully exerted, and the adhesion of microorganisms is synergistically prevented; the coating can be applied to the modification of the surface of a medical instrument, and the structural smoothness of the grafted coating can be ensured.)

1. The application of the non-release antimicrobial adhesive coating in the antibacterial medical appliance comprises grafting the borneol acrylate and the polyethylene glycol diacrylate to the surface of the medical appliance by a mode that the photoinitiator generates surface free radicals to be copolymerized to form the non-release antimicrobial adhesive coating, so as to obtain the medical appliance with the non-release antimicrobial adhesive coating; wherein, the polymer forming the non-release type antimicrobial adhesive coating is formed by copolymerizing two monomers of borneol acrylate and polyethylene glycol diacrylate, and the molecular structure is shown as the formula (I):

in the formula (I), n is the number of the repeating units of the polymer and takes the value of a positive integer;

the medical device is preferably a medical catheter made of polyamide, thermoplastic elastomer, polyurethane, polyvinyl chloride, polyethylene or polypropylene.

2. The use of claim 1, wherein the borneol acrylate is one or more of L-borneol acrylate, D-borneol acrylate and Iso-borneol acrylate; and/or the molecular weight of the polyethylene glycol diacrylate is 200-1000.

3. Use according to claim 2, wherein the non-releasing antimicrobial adhesive coating is capable of preventing fungal and bacterial adhesion; preferably, the molar ratio of the borneol acrylate to the polyethylene glycol diacrylate in the non-release antimicrobial adhesive coating layer is (0.3-3) to 1; further preferably, the molar fraction of the bornyl acrylate in the non-releasing antimicrobial adhesive coating is 0.25 to 0.75.

4. Use according to any one of claims 1 to 3, wherein the photoinitiator comprises benzophenone and/or isopropylthioxanthone; and/or the surface of the medical device comprises an inner surface of the medical device and an outer surface of the medical device.

5. The use according to any one of claims 1-4, characterized in that the use comprises,

step C, dispersing a photoinitiator solution on the surface of the medical instrument, and performing illumination, washing and drying in a nitrogen atmosphere to obtain the medical instrument with the surface modified by the photoinitiator;

d, dispersing the mixed solution of the borneol acrylate monomer and the polyethylene glycol diacrylate monomer on the surface of the medical apparatus of which the surface is modified by the photoinitiator, and performing illumination, washing and drying in nitrogen atmosphere to prepare the medical apparatus of which the surface is provided with the non-release antimicrobial adhesive coating;

wherein the surface of the medical device comprises an inner surface of a medical catheter and an outer surface of a medical catheter.

6. The use according to claim 5, wherein the photoinitiator solution is obtained by dissolving a photoinitiator in acetone, vortexing, sonicating, and then purging with nitrogen to remove oxygen; preferably, the concentration of the photoinitiator solution is 0.1-0.5 g/mL; further preferably, the photoinitiator comprises benzophenone and/or isopropyl thioxanthone.

7. The use according to claim 5 or 6, wherein the mixed solution of the borneol acrylate monomer and the polyethylene glycol diacrylate monomer is obtained by dissolving the borneol acrylate monomer and the polyethylene glycol diacrylate monomer in acetone, performing vortex treatment and ultrasonic treatment, and then introducing nitrogen to remove oxygen; preferably, in the mixed solution of the borneol acrylate monomer and the polyethylene glycol diacrylate monomer, the molar ratio of the borneol acrylate to the polyethylene glycol diacrylate is (0.3-3) to 1; further preferably, the concentration of the mixed solution of the bornyl acrylate monomer and the polyethylene glycol diacrylate monomer is 50% to 80% (v/v).

8. Use according to any one of claims 5 to 7,

the light source is a 200-1000W high-pressure mercury lamp, and the illumination time is 5-10 min;

and/or, in step C, the washing comprises soaking with an ethanol solution at room temperature for 5-10 h;

and/or, in the step D, the washing comprises soaking for 5-10 hours at room temperature by using dichloromethane and ethanol solution in sequence, and performing ultrasonic treatment for 20-30min after each soaking.

9. Use according to any one of claims 5 to 7, wherein in step C, the medical device is a pre-treated medical device; further preferably, the pretreatment method of the medical device comprises soaking in ethanol for 10 hours, performing ultrasonic treatment for 30min, washing with ethanol, and performing vacuum drying.

10. A medical device having a non-releasing antimicrobial adhesive coating on its surface, obtained in the use according to any one of claims 1 to 9.

Technical Field

The invention belongs to the field of biological materials, and relates to application of a non-release antimicrobial adhesive coating in an antibacterial medical instrument.

Background

The polymer base material is widely applied to life and industrial production of people, such as agriculture, food, medical treatment, chemical industry and the like. However, these polymers do not have the function of resisting microbial adhesion, provide a medium for adhesion and transmission of microorganisms, seriously affect the production efficiency and threaten the health of human beings. These problems of microbial contamination have been receiving attention from many researchers in recent years, and it is important to impart anti-microbial adhesion properties by modifying the surface of a polymer without damaging the internal structure of the polymer.

The preparation method of the conventional high-molecular antibacterial material mainly comprises two steps: one method is to add antibacterial components such as filling nano particles and adding antibacterial agents in the preparation process, and the method has high forming stability, but simultaneously, the difficulty of the production process is often increased, and the problem of low utilization rate of the antibacterial components exists; the other method is to load the antibacterial component on the surface after the polymer is processed and formed, which can improve the utilization rate of the antibacterial component, but has the problem that the durability of the antibacterial effect is poor as the antibacterial component is released.

For example, antimicrobial surfaces have a wide range of applications and values in medical devices. The invention of application No. 201711407609 provides an antibacterial coating for medical devices, whose main antibacterial components are antibacterial peptide and polyhexamethylene guanidine hydrochloride, having excellent antibacterial ability and very good surface adhesion property. The invention of application No. 201510131830 discloses a medical catheter, which fills bacteriostatic agent into the inner surface of the catheter to prevent the infection caused by the external bacteria entering into human body through the catheter. Application number 201911306494 discloses a medical antibacterial silica gel material, which contains antibacterial components mainly including nano silver and essential oil, and effectively improves the long-acting antibacterial property of the silica gel material. The antibacterial medical apparatus has the problems that along with the release of the antibacterial component, the durability of the antibacterial effect is poor, and even the use safety is affected by the released antibacterial component. In addition, it is difficult to combine the resistance to fungi and bacteria with the conventional antibacterial materials. Therefore, the production of medical devices with highly effective and stable non-releasing antimicrobial adhesive coatings has been an important goal of research and development in the industry.

In recent years, methods for introducing functional groups through ultraviolet light-assisted surface modification have attracted the interest of researchers. In 1996, poplar and Ranby invented a "two-step" living photografting method for polymers, under the condition of ultraviolet irradiation, a photoinitiator Benzophenone (BP) can abstract H atoms of C-H bonds on the surface of a substrate, so that surface free radicals are generated to initiate polymerization, the growth of a graft chain is realized, and terminal free radicals can be coupled with semipinacol free radicals generated by reduction of BP, so that controllable living surface grafting polymerization is realized (Macromolecules, 1996,29, 3308). Later, young and Yi et al found that Isopropyl Thioxanthone (ITX) with a structure similar to benzophenone also had similar properties and achieved grafting of polymeric substrates in the visible range. The ultraviolet light-induced surface technology was comprehensively described in "photoinitiation and surface modification" (polymer chemistry, 2001, chemical industry publishers) of the university of beijing chemical industry, and all vinyl monomers suitable for the process, such as acrylic acid, acrylic esters, acrylamide, etc., and photosensitizers suitable for the process, such as benzophenone, anthrone, etc., were indicated. The invention of application numbers 200310100364 and 200710146564 optimizes the method and achieves the aim of modifying the surfaces of various high polymer materials.

The invention of application No. 201410081985 discloses an antibacterial material of cellulose composite borneol, which uses borneol molecule to esterify and modify the macromolecular structure of cellulose, thereby realizing the aim of resisting microbial adhesion. The method is simple and easy to implement, and has good antibacterial performance. The invention of application No. 201910411303 discloses the use of borneol as a surface modifying component for textiles which are first surface modified with aminosilicone and then the aldehyde benzoic acid borneol is bonded to the surface of the textile. The invention can obtain stable and safe antimicrobial adhesion textile and has good anti-adhesion effect on fungi and bacteria.

At present, the research on the antimicrobial performance of the borneol only stays in that the substrate is modified by using the borneol alone and has obvious antibacterial effect, but the antibacterial performance of the surface of the modified material cannot be realized by carrying out photoinitiated polymerization on the acrylate monomer of the borneol (see a comparative example).

In addition, the modification method of the aforementioned patent is limited to groups with high reactivity, and the operation steps are relatively complicated, which results in unnecessary waste of resources in the production process. The active light grafting method can reduce the dosage of functional monomers, realize the application of most polymers in the field of antimicrobial adhesion, and has important significance for production and life.

Disclosure of Invention

The invention aims to provide an application of a non-release antimicrobial adhesive coating in an antibacterial medical device, and the non-release antimicrobial adhesive coating mainly composed of a copolymer of borneol acrylate and polyethylene glycol diacrylate is modified on the surface of the medical device to obtain the medical device with the non-release antimicrobial adhesive coating, and the medical device has excellent and lasting antibacterial performance.

The invention provides an application of a non-release antimicrobial adhesive coating in an antibacterial medical device, which comprises grafting the acrylic borneol ester and the polyethylene glycol diacrylate to the surface of the medical device in a manner that the photoinitiator generates surface free radicals to copolymerize the acrylic borneol ester and the polyethylene glycol diacrylate to form the non-release antimicrobial adhesive coating, so as to obtain the medical device with the non-release antimicrobial adhesive coating; wherein, the polymer forming the non-release type antimicrobial adhesive coating is formed by copolymerizing two monomers of borneol acrylate and polyethylene glycol diacrylate, and the molecular structure is shown as the formula (I):

in the formula (I), n is the number of the repeating units of the polymer and takes the value of a positive integer;

the medical device is preferably a medical catheter, and the material of the medical device comprises Polyamide (PA), thermoplastic elastomer (TPE), Polyurethane (PU), polyvinyl chloride (PVC), Polyethylene (PE) or polypropylene (PP).

In the invention, the borneol acrylate is one or more of L-borneol acrylate, D-borneol acrylate and Iso-borneol acrylate.

In the present invention, the molecular weight of the polyethylene glycol diacrylate is 200-1000.

According to the invention, the non-releasing antimicrobial adhesive coating is capable of preventing the adhesion of fungi and bacteria; preferably, the molar ratio of the borneol acrylate to the polyethylene glycol diacrylate in the non-release antimicrobial adhesive coating layer is (0.3-3) to 1; further preferably, the molar fraction of the bornyl acrylate in the non-releasing antimicrobial adhesive coating is 0.25 to 0.75.

In the present invention, the photoinitiator comprises benzophenone and/or isopropyl thioxanthone.

According to some embodiments of the invention, the application comprises,

step C, dispersing a photoinitiator solution on the surface of the medical instrument, and performing illumination, washing and drying in a nitrogen atmosphere to obtain the medical instrument with the surface modified by the photoinitiator;

d, dispersing the mixed solution of the borneol acrylate monomer and the polyethylene glycol diacrylate monomer on the surface of the medical apparatus of which the surface is modified by the photoinitiator, and performing illumination, washing and drying in nitrogen atmosphere to prepare the medical apparatus of which the surface is provided with the non-release antimicrobial adhesive coating;

wherein the surface of the medical device comprises an inner surface of a medical catheter and an outer surface of a medical catheter.

According to some embodiments of the invention, the photoinitiator solution is obtained by dissolving a photoinitiator in acetone, vortexing, sonicating, and then purging with nitrogen to remove oxygen; preferably, the concentration of the photoinitiator solution is 0.1-0.5 g/mL; further preferably, the photoinitiator comprises benzophenone and/or isopropyl thioxanthone.

According to other embodiments of the present invention, the mixed solution of the borneol acrylate monomer and the polyethylene glycol diacrylate monomer is obtained by dissolving the borneol acrylate monomer and the polyethylene glycol diacrylate monomer in acetone, performing vortex treatment and ultrasonic treatment, and then introducing nitrogen to remove oxygen; preferably, in the mixed solution of the borneol acrylate monomer and the polyethylene glycol diacrylate monomer, the molar ratio of the borneol acrylate to the polyethylene glycol diacrylate is (0.3-3) to 1; further preferably, the concentration of the mixed solution of the bornyl acrylate monomer and the polyethylene glycol diacrylate monomer is 50% to 80% (v/v).

In the invention, the light source is a 200-1000W high-pressure mercury lamp, and the illumination time is 5-10 min.

In some embodiments of the invention, in step C, the washing comprises soaking with an ethanol solution at room temperature for 5-10 h;

in other embodiments of the present invention, in step D, the washing comprises soaking with dichloromethane and ethanol solution sequentially for 5-10h at room temperature, and ultrasound is performed for 20-30min after each soaking.

According to the invention, in step C, the medical device is a pre-treated medical device; further preferably, the pretreatment method of the medical device comprises soaking in ethanol for 10 hours, performing ultrasonic treatment for 30min, washing with ethanol, and performing vacuum drying.

The present invention also provides a medical device having a non-releasing antimicrobial adhesive coating on the surface thereof, which is obtained in the above-mentioned application.

The invention provides an application of a non-release antimicrobial adhesive coating in an antibacterial medical appliance, wherein the main component of the non-release antimicrobial adhesive coating is formed by a copolymer of two monomers, namely, acrylic borneol ester (BA) and polyethylene glycol diacrylate (PEGDA), so that an amphiphilic stereochemical antibacterial high polymer coating is constructed, and the coating has good antimicrobial adhesion. The preparation method of the coating mainly comprises the following steps: firstly, preparing a monomer and a photoinitiator into a solution with a certain concentration, and then carrying out two-step modification on the medical instrument by using a photo-grafting method, wherein the photoinitiator is fixed on the surface of the medical instrument in the first step, and the monomer is initiated to polymerize through a surface free radical to realize grafting in the second step. The preparation method is simple, and the obtained grafted coating is safe and stable; the respective advantages of the polyacrylic borneol ester and the polyethylene glycol diacrylate can be fully exerted, and the adhesion of microorganisms is synergistically prevented; the coating is applied to surface modification of medical instruments, and can ensure the smooth structure of the grafted coating.

Drawings

The invention is described in further detail below with reference to the attached drawing figures:

FIG. 1 shows the molecular structure of the polymer constituting the non-release type antimicrobial adhesive coating layer.

FIG. 2 is a scanning electron microscope image of the grafted PBA-PPEGDA coating on the surface of the polypropylene film in example 2.

FIG. 3 is a schematic flow chart of the preparation of the non-release type antimicrobial adhesive coating layer according to the present invention.

FIG. 4 is a graph comparing the plate count results of the number of adherent bacteria (Staphylococcus aureus) on the surface of the hollow white medical catheter sample of example 5 with the surface of the medical catheter sample grafted with the PBA-PPEGDA coating.

Detailed Description

In order that the invention may be readily understood, a more particular description thereof will be rendered by reference to the appended drawings. However, before the invention is described in detail, it is to be understood that this invention is not limited to particular embodiments described. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

Where a range of values is provided, it is understood that each intervening value, to the extent that there is no stated or intervening value in that stated range, to the extent that there is no such intervening value, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where a specified range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

I. Term(s) for

The terms "about," "substantially," and "primarily," when used in conjunction with a range of components, concentrations, temperatures, or other physical or chemical properties or characteristics, as used herein, cover variations that may exist in the upper and/or lower limits of the range for the property or characteristic, including variations due to, for example, rounding, measurement, or other statistical variations. As used herein, numerical values associated with amounts, weights, and the like, are defined as all values for each particular value plus or minus 1%. For example, the term "about 10%" should be understood as "9% to 11%".

II. Detailed description of the preferred embodiments

As described above, in the two methods for preparing the polymer antibacterial material, the antibacterial component is added in the preparation process, the difficulty of the production process is high, and the utilization rate of the antibacterial component is not high; after the polymer is processed and formed, the surface is loaded with the antibacterial component, so that the problems that the antibacterial component is released, the effect durability is poor, and even the use safety is influenced by the released antibacterial component exist. In addition, it is difficult to combine the resistance to fungi and bacteria with the conventional antibacterial materials.

At present, the research on the antimicrobial performance of the borneol only stays in that the borneol is used alone to modify a base material, although the borneol has a remarkable antibacterial effect, the antibacterial performance of the surface of a grafting material cannot be realized by carrying out photoinitiated polymerization on an acrylate monomer of the borneol. The existing grafting method is limited to groups with high reactivity, and the operation steps are relatively complex, which can lead to unnecessary resource waste in the production process.

In view of the above, the present inventors have conducted extensive studies on a highly efficient and stable non-release type anti-microbial adhesion coating layer and a method for preparing the same. The invention researches and designs and discovers that the borneol-based non-release antibacterial polymer coating can be prepared by grafting the borneol acrylate and the polyethylene glycol diacrylate on the surface of the high polymer material and copolymerizing the borneol acrylate and the polyethylene glycol diacrylate, and the coating mainly comprises a copolymer of the borneol acrylate and the polyethylene glycol diacrylate and has good antibacterial performance. The present inventors have obtained the present invention by applying the non-releasing antimicrobial polymer coating to a medical device.

The application of the non-release antimicrobial adhesive coating in the antibacterial medical device can be understood as a method for grafting the non-release antimicrobial adhesive coating on the surface of the medical device, and the method comprises the following steps of grafting the borneol acrylate and the polyethylene glycol diacrylate on the surface of the medical device in a manner that a photoinitiator generates surface free radicals to form the non-release antimicrobial adhesive coating through copolymerization, so as to obtain the medical device with the non-release antimicrobial adhesive coating; wherein, the polymer forming the non-release type antimicrobial adhesive coating is formed by copolymerizing two monomers of bornyl acrylate and polyethylene glycol diacrylate, and the molecular structure is shown as the formula (I) (shown in figure 1):

in the formula (I), n is the number of the repeating units of the polymer and takes the value of a positive integer;

medical instrument includes that the material is Polyamide (PA), thermoplastic elastomer (TPE), Polyurethane (PU), polyvinyl chloride (PVC), Polyethylene (PE) or polypropylene (PP)'s medical catheter, just medical instrument's surface includes medical catheter's internal surface and medical catheter's surface.

In the invention, the borneol acrylate is one or more of L-borneol acrylate, D-borneol acrylate and Iso-borneol acrylate.

In the invention, the molecular weight of the polyethylene glycol diacrylate is 200-1000.

The invention creatively selects the hydrophilic polyethylene glycol diacrylate monomer as the annular complementary molecule to form the antimicrobial adhesion coating with local amphipathy, thereby realizing the effect of synergistically enhancing the antimicrobial adhesion.

In the present invention, the photoinitiator comprises benzophenone and/or isopropyl thioxanthone.

The inventors have conducted antimicrobial adhesion tests on non-releasing antimicrobial adhesion coatings and the results show that:

(1) when the molar ratio of the borneol acrylate to the polyethylene glycol diacrylate in the non-release antimicrobial adhesive coating is (0.3-3) to 1, the coating has excellent anti-adhesive effect on fungi; when the molar fraction of the borneol acrylate is less than 0.25 or more than 0.75, the antifungal adhesion effect is reduced to different degrees; in particular, when bornyl acrylate and polyethylene glycol diacrylate are used alone, a complete antifungal adhesion effect cannot be obtained.

(2) When the molar ratio of the borneol acrylate to the polyethylene glycol diacrylate in the non-release antimicrobial adhesive coating is (0.3-3) to 1, the antibacterial adhesive effect is optimal; in particular, when the bornyl acrylate and the polyethylene glycol diacrylate are used alone, a good anti-bacterial adhesion effect cannot be obtained.

As can be seen from the above, the non-releasing antimicrobial adhesive coating provided by the present invention is effective in inhibiting the adhesion of fungi and bacteria to its surface; preferably, the molar ratio of the borneol acrylate to the polyethylene glycol diacrylate in the non-release antimicrobial adhesive coating layer is (0.3-3) to 1; further preferably, the molar fraction of the bornyl acrylate in the non-releasing antimicrobial adhesive coating is 0.25 to 0.75.

The invention realizes the graft modification of PP or PET medical appliances. The antibacterial coating with a cross-linked structure is synthesized in two steps by an ultraviolet light grafting method. The coating is connected with the surface of the medical appliance through chemical bonds, and has good stability. The monomer of the acrylic acid borneol ester is used as a hydrophobic chain segment and a stereochemical chain segment, and the polyethylene glycol diacrylate is used as a hydrophilic chain segment. The hydrophilic chain segment is polyethylene glycol diacrylate, so that the grafting efficiency and the surface grafting flatness can be ensured, and therefore, the grafted coating with excellent performance can be prepared by adjusting the proportion of the polyethylene glycol diacrylate to the acrylic borneol ester.

From the above, it can be seen that the antimicrobial coating provided by the present invention is a non-release material, which affects the adhesion of microorganisms through the molecular structure of the coating surface, rather than releasing a bactericide, and is a safe and environment-friendly coating. Thus, the use of the non-releasing antimicrobial adhesive coating in antimicrobial medical devices of the present invention also includes the use of medical devices having a non-releasing antimicrobial adhesive coating in medical treatments where antimicrobial properties are desired.

The flow chart of the method for preparing the non-release type antimicrobial adhesive coating on the antibacterial medical device according to the invention is shown in figure 3, and as can be seen from figure 3, the method of the invention grafts the acrylic borneol ester and the polyethylene glycol diacrylate on the surface of the medical device with C-H bonds through the photoinitiator, and the acrylic borneol ester and the polyethylene glycol diacrylate are graft copolymerized on the surface of the medical device to form the non-release type antimicrobial adhesive coating.

The technical scheme for preparing the non-release antimicrobial adhesive coating is as follows:

(1) preparing photoinitiator solution and monomer mixed solution

Dissolving a photoinitiator in acetone, carrying out vortex treatment and ultrasonic treatment, and introducing nitrogen to remove oxygen to obtain a photoinitiator solution; preferably, the concentration of the photoinitiator solution is 0.1-0.5 g/mL; further preferably, the photoinitiator comprises benzophenone and/or isopropyl thioxanthone, and even more preferably, the photoinitiator is benzophenone and isopropyl thioxanthone.

Dissolving a borneol acrylate monomer and a polyethylene glycol diacrylate monomer in acetone, carrying out vortex treatment and ultrasonic treatment, and then introducing nitrogen to remove oxygen to obtain a mixed solution of the borneol acrylate monomer and the polyethylene glycol diacrylate monomer; preferably, in the mixed solution of the borneol acrylate monomer and the polyethylene glycol diacrylate monomer, the molar ratio of the borneol acrylate to the polyethylene glycol diacrylate is (0.3-3) to 1.

The concentration of the prepared mixed solution of the borneol acrylate monomer and the polyethylene glycol diacrylate monomer is 50-80% (v/v). This is understood to mean that the total volume of the two monomers, bornyl acrylate and polyethylene glycol diacrylate, is a percentage of the volume of the monomer mixture solution.

(2) Dispersing a photoinitiator solution on the surface of the medical instrument, and performing illumination, washing and drying in a nitrogen atmosphere to obtain the medical instrument with the surface modified by the photoinitiator;

(3) and dispersing the mixed solution of the acrylic borneol ester monomer and the polyethylene glycol diacrylate monomer on the surface of the medical instrument modified by the photoinitiator, and performing illumination, washing and drying in nitrogen atmosphere to prepare the medical instrument with the surface grafted with the non-release antimicrobial adhesive coating.

In some specific embodiments, in the step (2), Benzophenone (BP) and Isopropyl Thioxanthone (ITX) are used as the photoinitiators, the photoinitiators are dispersed and adsorbed on the surface of the medical device by dipping, coating or spraying, and the medical device modified by the photoinitiators is obtained by ultraviolet irradiation in a nitrogen atmosphere for a certain time.

In some further specific embodiments, the medical device is first soaked in ethanol and ultrasonically cleaned to remove impurities, and then vacuum dried for use. And then the prepared photoinitiator solution is subjected to ultrasonic treatment and is bubbled with nitrogen for a period of time, so that oxygen is fully dissolved and removed. Then, the photoinitiator is dispersed and adsorbed on the surface of the medical instrument by adopting a dipping or coating or spraying method, and is put into an acetone solution for soaking in a nitrogen atmosphere by ultraviolet irradiation for a period of time to remove the unreacted photoinitiator. And finally, drying the mixture in vacuum to obtain the medical appliance modified by the photoinitiator.

In other further specific embodiments, the acetone monomer mixed solution with a certain concentration is prepared by mixing the borneol acrylate and the polyethylene glycol diacrylate according to different proportions, and then the acetone monomer mixed solution is subjected to ultrasonic treatment and is bubbled with nitrogen for a period of time to fully remove oxygen. Then, the monomer mixed solution is dispersed and adsorbed on the surface of the medical apparatus with the surface modified by the photoinitiator by adopting a dipping or coating or spraying method, and the medical apparatus is irradiated by ultraviolet light for a period of time in nitrogen atmosphere, and then is sequentially put into dichloromethane and ethanol solution for soaking, and is subjected to ultrasonic treatment to remove the monomer and homopolymer which are not grafted. Finally, vacuum drying is carried out to obtain the medical appliance with the surface grafted with the non-release antimicrobial adhesive coating.

In some embodiments of the invention, specific methods for making medical devices having a non-release antimicrobial adhesive coating on the surface are as follows:

1. preparation work

(1) And (3) soaking the medical appliance in ethanol for 10h and performing ultrasonic treatment for 30min to remove impurities on the surface of the membrane, and drying to obtain the medical appliance to be modified.

(2) Preparing 0.1-0.5g/mL acetone solution from photoinitiator isopropyl thioxanthone and benzophenone according to the molar ratio of (1-5) to 1, performing ultrasonic treatment, and introducing nitrogen to remove oxygen.

(3) Preparing a solution with the molar ratio of the borneol acrylate to the polyethylene glycol diacrylate of (0.3-3) to 1 and the concentration of the monomer solution of 50-80% (volume fraction), and using the borneol acrylate and the polyethylene glycol diacrylate as controls, carrying out ultrasound, introducing nitrogen and removing oxygen.

2. The first step modification preparation process of the medical device is as follows:

dispersing and adsorbing the photoinitiator on the surface of the medical instrument by adopting a dipping or coating or spraying method, preheating by using a high-pressure mercury lamp for 1min, then rotationally irradiating the medical instrument for 5-10min in a nitrogen atmosphere, taking out the medical instrument, soaking the medical instrument in an ethanol solution for 5-10h, cleaning, drying, and removing the unreacted photoinitiator to obtain the medical instrument with the surface modified by the photoinitiator.

3. The second grafting preparation process of the medical appliance is as follows:

dispersing and adsorbing 50-200 mu L of monomer solution on the surface of a medical instrument by adopting a dipping or coating or spraying method, preheating for 1min by using a high-pressure mercury lamp, rotationally irradiating the medical instrument for 5-10min in a nitrogen atmosphere, sequentially putting the medical instrument into dichloromethane solution and ethanol solution, respectively cleaning for 5-10h, performing ultrasonic treatment for 20-30min each time to remove unreacted monomer and homopolymer, and drying and removing a solvent to obtain the medical instrument with the antimicrobial coating.

The invention combines the hydrophilic and hydrophobic chain segment with the stereochemical strategy through photo-grafting, is easy to implement, and can be applied to medical instruments with antimicrobial requirements.

In the present invention, the reaction efficiency is reflected by the graft ratio, which is calculated by the following formula:

percent grafting [ (% mass of membrane after grafting-mass of membrane before grafting)/total mass of monomer charged ] × 100%

The bacteriostasis or antibiosis test method of the invention is as follows:

determination of antifungal adhesion properties: cutting blank substrate material (such as medical catheter) and non-release type antimicrobial adhesion composite coating grafted substrate material into round samples with the diameter of 10.0 +/-0.1 mm, irradiating the round samples on the front side and the back side under an ultraviolet lamp for 1h for sterilization treatment, and then co-culturing the round samples with fungi.

Specifically, the membrane with composite coating layer is flatly pasted on malt extract agar culture medium with one side facing upwards, and then 10 μ L of fungus bacterial liquid (fungus spore liquid containing spore (1-5) × 10) is dripped at a position 1-2cm away from the material⁸Per mL]The substrate was incubated at a relative humidity of 85% + -5% at 30 ℃ for 8 days, and the surface of the substrate was observed and recorded with a camera as being contaminated. The evaluation standard of the mildew-proof effect is shown in table 1, wherein the coverage area of the mildew on the surface of the control sample is more than 60% (namely, the mildew-proof effect reaches 4 grades), and when the growth of the mildew on the surface of the blank test sample cannot be observed by eyes, the test is judged to be effective, otherwise, the test is invalid.

TABLE 1 evaluation criteria for mold-proofing effects

Growth of mold	Mildew resistance rating
		No obvious mildew growth under a magnifying glass	0
The mold grows rarely or locally, and the coverage area on the surface of the sample is less than 10 percent	1
		The coverage area of the mould on the surface of the sample is less than 30 percent (10 to 30 percent)	2
The coverage area of the mould on the surface of the sample is less than 60 percent (30-60 percent)	3
		The coverage area of the mould on the surface of the sample reaches or exceeds 60 percent	4

Determination of antibacterial adhesion properties: a blank substrate material (such as a medical catheter) and a non-release type antimicrobial adhesion composite coating grafted substrate material are cut into circular samples with the diameter of 10.0 +/-0.1 mm, are irradiated on the front side and the back side for 1h under an ultraviolet lamp for sterilization treatment, and then are cultured together with bacteria.

Specifically, the bacteria concentration was first prepared to be 10⁷CFU/mL PBS bacterial suspension, immersing blank substrate material and non-release type antimicrobial adhesion composite coating grafted substrate material into 1mL bacteria with concentration of 10⁷In the PBS bacterial suspension of CFU/mL, the materials are fully contacted and cultured for 24h at the temperature of 4 ℃, the materials are taken out, washed three times by sterile physiological saline and finally usedRemoving the cleaning solution by using filter paper, placing the filter paper in 1.8mL of sterile physiological saline, carrying out ultrasonic treatment for 15min, coating a 100 mu L plate, culturing the plate at 37 +/-2 ℃ for 24h, counting plate colonies, and calculating the antibacterial adhesion rate according to the formula (III):

R(％)＝[(A-B)/A]×100％ (III)

in the formula (III):

r-antibacterial adhesion rate of the sample;

a-surface bacteria adhesion quantity (CFU/mL) after the substrate material and bacterial liquid act for 24 hours;

and (3) the surface bacterial adhesion quantity (CFU/mL) of the B-non-release antimicrobial adhesion coating grafted substrate material after 24 hours of bacterial liquid action.

Examples

The present invention will be specifically described below with reference to specific examples. The experimental methods described below are, unless otherwise specified, all routine laboratory procedures. The experimental materials described below, unless otherwise specified, are commercially available.

The strains for antifungal experiments or antibacterial experiments include:

aspergillus niger (ATCC 16404); staphylococcus aureus (Staphylococcus aureus) (ATCC 25923); wherein the term "ATCC" refers to American Type Culture Collection. All the strains are purchased from China industrial microorganism strain preservation management center, and each strain is independently used as an experimental strain to carry out antifungal experiment or antibacterial experiment on a sample to be tested.

Malt extract (wort) agar medium used in antifungal experiments, nutrient agar medium used for bacterial count in antibacterial experiments, and TSB medium (trypticase soytone broth) used for preparing bacterial solutions were purchased from beijing obozocent biotechnology ltd.

Example 1:

preparation of grafted PBA-PPEGDA coating of polyacrylonitrile membrane:

(1) preparation of solutions

Preparation of photoinitiator solution: 4.2300g of isopropyl thioxanthone and 0.6066g of benzophenone are weighed in a brown sample bottle, then 10mL of acetone is added, vortex and ultrasonic treatment are carried out for 20min to fully dissolve the acetone, and finally the acetone is bubbled for 20min by a nitrogen blower (ND400, Hangzhou Ruichi instruments, Inc.) to fully remove oxygen to obtain the photoinitiator solution.

Preparation of monomer solution: after 2.08mL of BA and 2.00mL of PEGDA (relative molecular weight 200) are mixed uniformly (the molar ratio of BAP to PEGDA is 1: 1), 0.8mL of mixed monomer and 0.2mL of acetone are sucked and placed in a brown sample bottle for ultrasonic treatment, and then nitrogen is introduced to remove oxygen for 20min, so as to obtain a monomer solution.

(2) Preparation of photoinitiator-modified Polyacrylonitrile membranes

Soaking polyacrylonitrile membrane in ethanol for 10 hr, ultrasonic treating for 30min to remove impurities, washing surface with ethanol, and vacuum drying. The quartz plate is placed on the bottom layer to be used as a support, and the polyacrylonitrile film is covered on the quartz plate. And (3) sucking 100 mu L of photoinitiator solution by using a pipette gun to drop on the surface of the membrane, covering a quartz plate on the membrane, and slightly pressing to remove bubbles to form a liquid interlayer. After preheating by a high-pressure mercury lamp for 1min, the obtained reaction device model is placed under the high-pressure mercury lamp for irradiation for 8 min. And taking out the model, soaking the model in an acetone solution for 10 hours, putting the model into a vacuum drying oven for drying, and removing the unreacted photoinitiator and solvent to obtain the photoinitiator modified polyacrylonitrile membrane.

(3) Preparation of Polyacrylonitrile Membrane with PBA-PPEGDA coating

Dispersing 100 mu L of monomer solution on the surface of the membrane according to the reaction model in the step (2), irradiating for 8min, sequentially putting the reaction device into dichloromethane solution and ethanol solution, respectively cleaning for 10h, performing ultrasonic treatment for 30min after soaking each time to remove unreacted monomers and homopolymers, and drying to remove the solvent to obtain the polyacrylonitrile membrane with the PBA-PPEGDA coating, wherein the grafting efficiency of the monomers reaches 50 percent.

Determination of antifungal adhesion properties:

cutting the polyacrylonitrile membrane with the coating and the ungrafted membrane into a wafer with the diameter of 1cm, irradiating the front side and the back side of the wafer for 1h under an ultraviolet lamp for sterilization, then co-culturing the wafer and aspergillus niger in the same wort agar culture medium, enabling the side of the wafer with the grafting layer to face upwards, dripping 10 mu L of aspergillus niger spore liquid at a position 1-2cm away from the material, and culturing for 8 days to observe the pollution condition of the surface of the material. The results show that no obvious mildew grows under the magnifier, and the magnifier has excellent antifungal adhesion effect corresponding to the mildew-proof grade of 0.

Comparative example 1: preparation of grafted PBA coating of polyacrylonitrile membrane:

(1) preparation of solutions

Preparation of photoinitiator solution: 4.2300g of isopropyl thioxanthone and 0.6066g of benzophenone are weighed in a brown sample bottle, then 10mL of acetone is added, vortex is carried out, ultrasonic treatment is carried out for 20min to fully dissolve the acetone, finally, a nitrogen blowing instrument is used for bubbling for 20min, and oxygen is fully removed to obtain the photoinitiator solution.

Preparation of monomer solution: 0.8mL of BA and 0.2mL of acetone were mixed and placed in a brown sample bottle for sonication, followed by purging with nitrogen for 20min to obtain a monomer solution (BAP to PEGDA molar ratio of 1: 0).

(2) Preparation of photoinitiator-modified Polyacrylonitrile membranes

Soaking polyacrylonitrile membrane in ethanol for 10 hr, ultrasonic treating for 30min to remove impurities, washing surface with ethanol, and vacuum drying. The quartz plate is placed on the bottom layer to be used as a support, and the polyacrylonitrile film is covered on the quartz plate. And (3) sucking 100 mu L of photoinitiator solution by using a pipette gun to drop on the surface of the membrane, covering a quartz plate on the membrane, and slightly pressing to remove bubbles to form a liquid interlayer. After preheating by a high-pressure mercury lamp for 1min, the obtained reaction device model is placed under the high-pressure mercury lamp for irradiation for 8 min. And taking out the model, soaking the model in an acetone solution for 10 hours, putting the model into a vacuum drying oven for drying, and removing the unreacted photoinitiator and solvent to obtain the photoinitiator modified polyacrylonitrile membrane.

(3) Preparation of Polyacrylonitrile membranes with PBA coatings

And (3) dispersing 100 mu L of monomer solution on the surface of the membrane according to the reaction model in the step (2), irradiating for 8min, putting the reaction device into dichloromethane solution, cleaning for 10h, soaking, performing ultrasonic treatment for 30min to remove unreacted monomers and homopolymers, drying and removing the solvent to obtain the polyacrylonitrile membrane with the PBA coating, wherein the grafting efficiency of the monomers is 1.6%.

Determination of antifungal adhesion properties:

cutting the polyacrylonitrile membrane with the coating and the ungrafted membrane into a wafer with the diameter of 1cm, irradiating the front side and the back side of the wafer for 1h under an ultraviolet lamp for sterilization, then co-culturing the wafer and aspergillus niger in the same wort agar culture medium, enabling the side of the wafer with the grafting layer to face upwards, dripping 10 mu L of aspergillus niger spore liquid at a position 1-2cm away from the material, and culturing for 8 days to observe the pollution condition of the surface of the material. The results show that the mould coverage on the surface of the sample is 27.3%, corresponding to mould proof grade 2, it fails to achieve a complete antifungal adhesion effect.

Comparative example 2:

preparation of a grafted PPEGDA coating of a polyacrylonitrile membrane:

(1) preparation of solutions

Preparation of photoinitiator solution: 4.2300g of isopropyl thioxanthone and 0.6066g of benzophenone are weighed in a brown sample bottle, then 10mL of acetone is added, vortex is carried out, ultrasonic treatment is carried out for 20min to fully dissolve the acetone, finally, a nitrogen blowing instrument is used for bubbling for 20min, and oxygen is fully removed to obtain the photoinitiator solution.

Preparation of monomer solution: 0.8mL of PEGDA (relative molecular weight 200) and 0.2mL of acetone were mixed and placed in a brown sample bottle for sonication, followed by purging with nitrogen for 20min to obtain a monomer solution (mole ratio of BAP to PEGDA is 0: 1).

(2) Preparation of photoinitiator modified polyacrylonitrile membrane the polyacrylonitrile membrane is soaked in ethanol for 10h, and is ultrasonically treated for 30min to remove impurities, the surface is washed with ethanol, and vacuum drying is carried out. The quartz plate is placed on the bottom layer to be used as a support, and the polyacrylonitrile film is covered on the quartz plate. And (3) sucking 100 mu L of photoinitiator solution by using a pipette gun to drop on the surface of the membrane, covering a quartz plate on the membrane, and slightly pressing to remove bubbles to form a liquid interlayer. After preheating by a high-pressure mercury lamp for 1min, the obtained reaction device model is placed under the high-pressure mercury lamp for irradiation for 8 min. And taking out the model, soaking the model in an acetone solution for 10 hours, putting the model into a vacuum drying oven for drying, and removing the unreacted photoinitiator and solvent to obtain the photoinitiator modified polyacrylonitrile membrane.

(3) Preparation of Polyacrylonitrile Membrane with a PPEGDA coating

And (3) dispersing 100 mu L of monomer solution on the surface of the membrane according to the reaction model in the step (2), irradiating for 8min, putting the reaction device into ethanol solution, cleaning for 10h, soaking, performing ultrasonic treatment for 30min to remove unreacted monomers and homopolymers, drying and removing the solvent to obtain the polyacrylonitrile membrane with the PPEGDA coating, wherein the grafting efficiency of the monomers is 53%.

Determination of antifungal adhesion properties:

cutting the polyacrylonitrile membrane with the coating and the ungrafted membrane into a wafer with the diameter of 1cm, irradiating the front side and the back side of the wafer for 1h under an ultraviolet lamp for sterilization, then co-culturing the wafer and aspergillus niger in the same wort agar culture medium, enabling the side of the wafer with the grafting layer to face upwards, dripping 10 mu L of aspergillus niger spore liquid at a position 1-2cm away from the material, and culturing for 8 days to observe the pollution condition of the surface of the material. The mold coverage on the sample surface was 3.9%, corresponding to mold resistance rating 1, which did not fully exert the antifungal adhesion effect.

Example 2: preparation of grafted PBA-PPEGDA coating of polyethylene film:

(1) preparation of solutions

Preparation of photoinitiator solution: 2.5400g of isopropyl thioxanthone and 1.8220g of benzophenone are weighed in a brown sample bottle, then 10mL of acetone is added, vortex is carried out, ultrasonic treatment is carried out for 20min to fully dissolve the acetone, finally, a nitrogen blowing instrument is used for bubbling for 20min, and oxygen is fully removed to obtain the photoinitiator solution.

Preparation of monomer solution: after 2.08mLBA and 4.00mLPEGDA (relative molecular weight 400) are mixed uniformly (the molar ratio of BAP to PEGDA is 1: 1), 0.65mL of mixed monomer and 0.35mL of acetone are sucked and placed in a brown sample bottle for ultrasonic treatment, and then nitrogen is introduced to remove oxygen for 20min, so that a monomer solution is obtained.

(2) Preparation of photoinitiator modified polyethylene film

Soaking polyethylene film in acetone for 10 hr, ultrasonic treating for 30min to remove impurities, washing surface with acetone, and vacuum drying. The quartz plate is placed on the bottom layer to be used as a support, and the quartz plate is covered with a polyethylene film. And (3) sucking 100 mu L of photoinitiator solution by using a pipette gun to drop on the surface of the membrane, covering a quartz plate on the membrane, and slightly pressing to remove bubbles to form a liquid interlayer. After preheating by a high-pressure mercury lamp for 1min, the obtained reaction device model is placed under the high-pressure mercury lamp for irradiation for 8 min. And taking out the model, soaking the model in an acetone solution for 10 hours, putting the model into a vacuum drying oven for drying, and removing the unreacted photoinitiator and solvent to obtain the photoinitiator modified polyethylene film.

(3) Preparation of polyethylene film with PBA-PPEGDA coating

And (3) dispersing 100 mu L of monomer solution on the surface of the membrane according to the reaction model in the step (2), irradiating for 8min, sequentially putting the reaction device into dichloromethane solution and ethanol solution, respectively cleaning for 10h, performing ultrasonic treatment for 30min after each soaking to remove unreacted monomers and homopolymers, and drying to remove the solvent to obtain the polyethylene membrane with the single-sided PBA-PPEGDA coating.

Grafting is carried out on one side of the ungrafted coating layer according to the same mode to obtain the polyethylene film with the double-sided PBA-PPEGDA coating layer, and the grafting efficiency of the monomer is 94.6%. The reaction has the advantages of simple operation and high reaction efficiency.

The PBA-PPEGDA coating prepared by adopting a scanning electron microscope (Hitachi S-4700 scanning electron microscope, Hitachi, Japan) is observed, and the result is shown in figure 2, so that an obvious grafting layer structure can be observed, which indicates that the PBA-PPEGDA coating is successfully synthesized.

Determination of antifungal adhesion properties:

cutting the blank polyethylene film and the polyethylene film modified by the non-release antimicrobial adhesive composite coating into round samples with the diameter of 10.0 +/-0.1 mm, irradiating the round samples for 1 hour on the front and back sides under an ultraviolet lamp for sterilization, and then culturing the round samples and fungi for 8 days to observe the pollution condition of the surface of the material. The modified film surface has no obvious mildew growth, and has excellent antifungal adhesion effect corresponding to the mildew-proof grade 0.

Determination of antibacterial adhesion properties:

cutting the polyethylene film with coating and ungrafted polyethylene film into round pieces with diameter of 1cm, irradiating under ultraviolet lamp for 1 hr for sterilizationTreatment, followed by co-culture with Staphylococcus aureus. Firstly, staphylococcus aureus 10 is prepared⁷And (3) immersing 1mL of PBS bacterial suspension into the CFU/mL of PBS bacterial suspension, fully contacting the material at 4 ℃ for co-culturing for 24h, taking out the material, washing the material with sterile physiological saline for three times, removing a washing liquid by using filter paper, placing the material in 1.8mL of sterile physiological saline, carrying out ultrasonic treatment for 15min, coating a 100 mu L plate, culturing for 24h at 37 ℃, and calculating the colony number of the plate. The antibacterial adhesion rate to staphylococcus aureus is 99.89%.

Comparative example 3:

preparation of grafted PBA coating of polyethylene film:

(1) preparation of solutions

Preparation of photoinitiator solution: 2.5400g of isopropyl thioxanthone and 1.8220g of benzophenone are weighed in a brown sample bottle, then 10mL of acetone is added, vortex is carried out, ultrasonic treatment is carried out for 20min to fully dissolve the acetone, finally, a nitrogen blowing instrument is used for bubbling for 20min, and oxygen is fully removed to obtain the photoinitiator solution.

Preparation of monomer solution: 0.65mL of BA and 0.35mL of acetone were mixed and placed in a brown sample bottle for sonication, followed by purging with nitrogen for 20min to obtain a monomer solution (BAP to PEGDA molar ratio of 1: 0).

(2) Preparation of photoinitiator modified polyethylene film

Soaking polyethylene film in acetone for 10 hr, ultrasonic treating for 30min to remove impurities, washing surface with acetone, and vacuum drying. The quartz plate is placed on the bottom layer to be used as a support, and the quartz plate is covered with a polyethylene film. And (3) sucking 100 mu L of photoinitiator solution by using a pipette gun to drop on the surface of the membrane, covering a quartz plate on the membrane, and slightly pressing to remove bubbles to form a liquid interlayer. After preheating by a high-pressure mercury lamp for 1min, the obtained reaction device model is placed under the high-pressure mercury lamp for irradiation for 8 min. And taking out the model, soaking the model in an acetone solution for 10 hours, putting the model into a vacuum drying oven for drying, and removing the unreacted photoinitiator and solvent to obtain the photoinitiator modified polyethylene film.

(3) Preparation of polyethylene film with PBA coating

And (3) dispersing 100 mu L of monomer solution on the surface of the film according to the reaction model in the step (2), irradiating for 8min, putting the reaction device into dichloromethane solution, cleaning for 10h, soaking, performing ultrasonic treatment for 30min to remove unreacted monomers and homopolymers, and drying to remove the solvent to obtain the polyethylene film with the single-sided PBA coating.

Grafting is carried out on one side of the ungrafted coating layer according to the same mode to obtain the polyethylene film with the double-sided PBA coating layer, and the grafting efficiency of the monomer is 30.0%.

Determination of antifungal adhesion properties:

cutting blank polyethylene film and PBA coating modified polyethylene film into round samples with diameter of 10.0 +/-0.1 mm, irradiating the round samples for 1 hour on the front and back sides under an ultraviolet lamp for sterilization, and co-culturing the round samples with fungi for 8 days to observe the pollution condition of the surface of the material. Mold was observed in both the blank film and the polyethylene film modified with the PBA coating, and no complete antifungal adhesion effect was achieved corresponding to a mold resistance level of 1.

Determination of antibacterial adhesion properties:

cutting the polyethylene film with the coating and the polyethylene film without grafting into round pieces with the diameter of 1cm, irradiating the round pieces on the front and back sides under an ultraviolet lamp for 1h for sterilization, and then co-culturing with staphylococcus aureus. Firstly, the concentration of staphylococcus aureus is prepared to be 10⁷And (3) immersing 1mL of PBS bacterial suspension into the CFU/mL of PBS bacterial suspension, fully contacting the material at 4 ℃ for co-culturing for 24h, taking out the material, washing the material with sterile physiological saline for three times, removing a washing liquid by using filter paper, placing the material in 1.8mL of sterile physiological saline, carrying out ultrasonic treatment for 15min, coating a 100 mu L plate, culturing for 24h at 37 ℃, and calculating the colony number of the plate.

The result shows that the polyethylene film with the grafted coating layer has a certain antibacterial adhesion effect, but the antibacterial adhesion effect is poor, and the antibacterial adhesion rate to staphylococcus aureus is 84.3%.

Comparative example 4:

preparation of grafted PEGDA coating of polyethylene film:

(1) solution preparation photoinitiator solution preparation: 2.5400g of isopropyl thioxanthone and 1.8220g of benzophenone are weighed in a brown sample bottle, then 10mL of acetone is added, vortex is carried out, ultrasonic treatment is carried out for 20min to fully dissolve the acetone, finally, a nitrogen blowing instrument is used for bubbling for 20min, and oxygen is fully removed to obtain the photoinitiator solution.

Preparation of monomer solution: 0.65mL of PEGDA (relative molecular weight 400) and 0.35mL of acetone were mixed and placed in a brown sample bottle for sonication, followed by purging with nitrogen for 20min to obtain a monomer solution (mole ratio of BAP to PEGDA is 0: 1).

(2) Preparation of photoinitiator modified polyethylene film

Soaking polyethylene film in acetone for 10 hr, ultrasonic treating for 30min to remove impurities, washing surface with acetone, and vacuum drying. The quartz plate is placed on the bottom layer to be used as a support, and the quartz plate is covered with a polyethylene film. And (3) sucking 100 mu L of photoinitiator solution by using a pipette gun to drop on the surface of the membrane, covering a quartz plate on the membrane, and slightly pressing to remove bubbles to form a liquid interlayer. After preheating by a high-pressure mercury lamp for 1min, the obtained reaction device model is placed under the high-pressure mercury lamp for irradiation for 8 min. And taking out the model, soaking the model in an acetone solution for 10 hours, putting the model into a vacuum drying oven for drying, and removing the unreacted photoinitiator and solvent to obtain the photoinitiator modified polyethylene film.

(3) Preparation of polyethylene film with PPEGDA coating

And (3) dispersing 100 mu L of monomer solution on the surface of the membrane according to the reaction model in the step (2), irradiating for 8min, putting the reaction device into ethanol solution, cleaning for 10h, soaking, performing ultrasonic treatment for 30min to remove unreacted monomers and homopolymers, and drying to remove the solvent to obtain the polyethylene membrane with the single-sided PEGDA coating.

The grafting was carried out in the same manner on the side of the ungrafted coating, obtaining a polyethylene film with a double-sided PPEGDA coating, the grafting efficiency of the monomer being 93.4%.

Determination of antifungal adhesion properties:

cutting the blank polyethylene film and the polyethylene film modified by the PPEGDA coating into round samples with the diameter of 10.0 +/-0.1 mm, irradiating the round samples for 1 hour on the front and back sides under an ultraviolet lamp for sterilization, and then culturing the round samples and fungi for 8 days to observe the pollution condition on the surface of the material. Mould is observed on both the blank film and the polyethylene film modified by the PPEGDA coating, and the complete antifungal adhesion effect is not achieved corresponding to the mildew-proof grade 1.

Determination of antibacterial adhesion properties:

cutting the polyethylene film with the coating and the polyethylene film without grafting into round pieces with the diameter of 1cm, irradiating the round pieces on the front and back sides under an ultraviolet lamp for 1h for sterilization, and then co-culturing with staphylococcus aureus. Firstly, the concentration of staphylococcus aureus is prepared to be 10⁷And (3) immersing 1mL of PBS bacterial suspension into the CFU/mL of PBS bacterial suspension, fully contacting the material at 4 ℃ for co-culturing for 24h, taking out the material, washing the material with sterile physiological saline for three times, removing a washing liquid by using filter paper, placing the material in 1.8mL of sterile physiological saline, carrying out ultrasonic treatment for 15min, coating a 100 mu L plate, culturing for 24h at 37 ℃, and calculating the colony number of the plate. The antibacterial adhesion rate to staphylococcus aureus is 86.1%.

Example 3:

preparation of grafted PBA-PPEGDA coating of polyethylene terephthalate film:

(1) solution preparation photoinitiator solution preparation: weighing 0.84g of isopropyl thioxanthone and 3.0333g of benzophenone in a brown sample bottle, adding 10mL of acetone, carrying out vortex, carrying out ultrasonic treatment for 20min to fully dissolve the acetone, and finally carrying out bubbling for 20min by using a nitrogen blower to fully remove oxygen to obtain a photoinitiator solution.

Preparation of monomer solution: dissolving 1.56mLBA and 2.50mLPEGDA (relative molecular weight 1000) (BAP/PEGDA molar ratio of 3: 1) by ultrasonic wave, sucking 0.5mL of mixed monomer and 0.5mL of acetone, placing in a brown sample bottle, performing ultrasonic treatment, introducing nitrogen to remove oxygen for 20min, and obtaining a monomer solution.

(2) Preparation of photoinitiator-modified polyethylene terephthalate film

Soaking polyethylene terephthalate film in ethanol for 10h, performing ultrasonic treatment for 30min to remove impurities, washing the surface with ethanol, and vacuum drying. The quartz plate is placed on the bottom layer to be used as a support, and the quartz plate is covered with a polyethylene terephthalate film. And (3) sucking 100 mu L of photoinitiator solution by using a pipette gun to drop on the surface of the membrane, covering a quartz plate on the membrane, and slightly pressing to remove bubbles to form a liquid interlayer. After preheating by a high-pressure mercury lamp for 1min, the obtained reaction device model is placed under the high-pressure mercury lamp for irradiation for 5 min. And taking out the model, soaking the model in an acetone solution for 5 hours, putting the model into a vacuum drying oven for drying, and removing the unreacted photoinitiator and solvent to obtain the photoinitiator modified polyethylene terephthalate film.

(3) Preparation of polyethylene terephthalate film with PBA-PPEGDA coating

Dispersing 100 mu L of monomer solution on the surface of the membrane according to the reaction model in the step (2), irradiating for 5min, sequentially putting the reaction device into dichloromethane solution and ethanol solution, respectively cleaning for 5h, performing ultrasonic treatment for 20min after soaking each time to remove unreacted monomers and homopolymers, and drying to remove the solvent to obtain the polyethylene terephthalate membrane with the PBA-PPEGDA coating, wherein the grafting efficiency of the monomers reaches 90 percent.

Determination of antifungal adhesion properties:

cutting the polyethylene terephthalate film with the coating and the ungrafted film into a circular sheet with the diameter of 1cm, irradiating the circular sheet with ultraviolet lamps for 1 hour on the front side and the back side for sterilization, co-culturing the circular sheet and aspergillus niger in the same wort agar culture medium, enabling the side of the circular sheet with the grafting layer to face upwards, placing the circular sheet at a position 1-2cm away from the center of a culture dish, dropwise adding 10 mu L of aspergillus niger spore solution into the center of the culture dish, and culturing for 8 days to observe the pollution condition of the surface of the material. The result reaches the mildew-proof grade of 0, and the antifungal adhesive has excellent antifungal adhesive effect.

Example 4: preparation of grafted PBA-PPEGDA coating of polypropylene film:

(1) solution preparation:

preparation of photoinitiator solution: 0.6600g of isopropyl thioxanthone and 0.3400g of benzophenone are weighed into a brown sample bottle, then 10mL of acetone is added, vortex is carried out, ultrasonic treatment is carried out for 20min to fully dissolve the acetone, finally, a nitrogen blowing instrument is used for bubbling for 20min, oxygen is fully removed, and the photoinitiator solution is obtained.

Preparation of monomer solution: mixing 1.04mLBA and 3.00mLPEGDA (relative molecular weight 200) (mole ratio of BAP to PEGDA is 1: 3), sucking 0.8mL of mixed monomer and 0.2mL of acetone, placing in a brown sample bottle, performing ultrasonic treatment, introducing nitrogen to remove oxygen for 20min, and obtaining a monomer solution.

(2) Preparation of photoinitiator-modified Polyacrylonitrile membranes

Soaking the polypropylene film in ethanol for 10h, performing ultrasonic treatment for 30min to remove impurities, washing the surface with ethanol, and vacuum drying. The quartz plate is placed on the bottom layer to be used as a support, and the quartz plate is covered with a polypropylene film. And (3) sucking 100 mu L of photoinitiator solution by using a pipette gun to drop on the surface of the membrane, covering a quartz plate on the membrane, and slightly pressing to remove bubbles to form a liquid interlayer. After preheating by a high-pressure mercury lamp for 1min, the obtained reaction device model is placed under the high-pressure mercury lamp for irradiation for 10 min. And taking out the model, soaking the model in an acetone solution for 8 hours, putting the model into a vacuum drying oven for drying, and removing the unreacted photoinitiator and solvent to obtain the photoinitiator modified polypropylene film.

(3) Preparation of Polyacrylonitrile Membrane with PBA-PPEGDA coating

And (3) dispersing 100 mu L of monomer solution on the surface of the membrane according to the reaction model in the step (2), irradiating for 10min, sequentially putting the reaction device into dichloromethane solution and ethanol solution, respectively cleaning for 8h, performing ultrasonic treatment for 25min after each soaking to remove unreacted monomers and homopolymers, and drying to remove the solvent to obtain the polypropylene membrane with the PBA-PPEGDA coating. After the reaction, it was observed that the monomer remained without any liquid and was completely graft-fixed to the surface of the substrate. The reaction has the advantages of simple operation and high reaction efficiency.

Determination of antifungal adhesion properties:

cutting the polypropylene film with the coating and the ungrafted film into round pieces with the diameter of 1cm, irradiating the round pieces for 1h under an ultraviolet lamp for sterilization treatment, then co-culturing the round pieces with the aspergillus niger in the same wort agar culture medium, enabling the side of the membrane with the grafting layer to face upwards, placing the membrane at a position 1-2cm away from the center of a culture dish, then dropwise adding 10 mu L of aspergillus niger spore liquid into the center of the culture dish, and culturing for 8 days to observe the pollution condition of the surface of the material. The result reaches the mildew-proof grade of 0, and the antifungal adhesive has excellent antifungal adhesive effect.

Example 5:

preparation of medical catheter with PBA-PPEGDA coating grafted on the surface:

(1) solution preparation:

preparation of photoinitiator solution: 4.2300g of isopropyl thioxanthone and 0.6066g of benzophenone are weighed in a brown sample bottle, then 10mL of acetone is added, vortex is carried out, ultrasonic treatment is carried out for 20min to fully dissolve the acetone, finally, a nitrogen blowing instrument is used for bubbling for 20min, and oxygen is fully removed to obtain the photoinitiator solution.

Preparation of monomer solution: after 2.08mL of BA and 2.00mL of PEGDA (relative molecular weight 200) are mixed uniformly (the molar ratio of BAP to PEGDA is 1: 1), 0.8mL of mixed monomer and 0.2mL of acetone are sucked and placed in a brown sample bottle for ultrasonic treatment, and then nitrogen is introduced to remove oxygen for 20min, so as to obtain a monomer solution.

(2) Preparation of medical catheter with surface modified by photoinitiator

Soaking the medical catheter in ethanol for 10h, performing ultrasonic treatment for 30min to remove impurities, washing the surface with ethanol, and vacuum drying. The method comprises the steps of dispersing and adsorbing a photoinitiator solution on the inner surface and the outer surface of the medical catheter by adopting a dipping or coating or spraying method, preheating the medical catheter by a high-pressure mercury lamp for 1min, rotationally irradiating the medical catheter for 8min in a nitrogen atmosphere, taking out the medical catheter and soaking the medical catheter in an acetone solution for 10h to obtain the medical catheter made of PP/PET materials with the surface modified by the photoinitiator.

(3) Preparation of PP/PET medical catheter with PBA-PPEGDA coating on surface

And (3) dispersing and adsorbing the monomer solution on the inner surface and the outer surface of the medical catheter by adopting a dipping or coating or spraying method according to the mode of the step (2), preheating for 1min by using a high-pressure mercury lamp, rotationally irradiating the medical catheter for 8min in a nitrogen atmosphere, taking out the medical catheter, sequentially putting the medical catheter into a dichloromethane solution and an ethanol solution for respectively cleaning for 10h, performing ultrasonic treatment for 30min after each soaking, removing unreacted monomers and homopolymers, and drying and removing the solvent to obtain the medical catheter with the PBA-PPEGDA coating. After the reaction, the monomer is observed to be not remained and not exist in a liquid form after the reaction, and all the monomer is grafted and fixed on the surface of the medical catheter. The reaction has the advantages of simple operation and high reaction efficiency.

Determination of antifungal adhesion properties:

cutting the blank medical catheter and the non-release type antimicrobial adhesion coating modified medical catheter into round samples with the diameter of 10.0 +/-0.1 mm, irradiating the front side and the back side of the round samples for 1 hour under an ultraviolet lamp for sterilization, and then culturing the round samples and fungi for 8 days to observe the pollution condition of the surface of the material. No obvious mildew growth occurs under a magnifying glass, and the corresponding mildew-proof grade is 0, so that the antifungal adhesive has an excellent antifungal adhesive effect.

Determination of antibacterial adhesion properties:

cutting the blank medical catheter and the non-release type antimicrobial adhesion coating modified medical catheter into a circular sheet with the diameter of 1cm, irradiating the front side and the back side of the circular sheet for 1 hour under an ultraviolet lamp for sterilization, and then co-culturing the circular sheet and staphylococcus aureus. Firstly, the concentration of staphylococcus aureus is prepared to be 10⁷And (3) immersing 1mL of PBS bacterial suspension into the CFU/mL of PBS bacterial suspension, fully contacting the material at 4 ℃ for co-culturing for 24h, taking out the material, washing the material with sterile physiological saline for three times, removing a washing liquid by using filter paper, placing the material in 1.8mL of sterile physiological saline, carrying out ultrasonic treatment for 15min, coating a 100 mu L plate, culturing for 24h at 37 ℃, and calculating the colony number of the plate. The results show that the non-release antimicrobial adhesion coating modified medical catheter has 99.70% of antimicrobial adhesion to staphylococcus aureus (see fig. 4).

It should be noted that the above-mentioned embodiments are only for explaining the present invention, and do not constitute any limitation to the present invention. The present invention has been described with reference to exemplary embodiments, but the words which have been used herein are words of description and illustration, rather than words of limitation. The invention can be modified, as prescribed, within the scope of the claims and without departing from the scope and spirit of the invention. Although the invention has been described herein with reference to particular means, materials and embodiments, the invention is not intended to be limited to the particulars disclosed herein, but rather extends to all other methods and applications having the same functionality.