TWI629320B - An antibiofouling material and its preparation - Google Patents

Abstract

The invention provides an anti-biomolecular adhesive material comprising a substrate and a coating layer, wherein the coating layer is fixed on the surface of the substrate by a covalent bond, and a manufacturing method thereof. Wherein the coating layer comprises a copolymer of a monomer having an epoxy group and a monomer having a diionic functional group. Secondly, the present invention also provides a method of producing the biomolecule-adhesive material.

Description

Antibiotic bioadhesive material and manufacturing method thereof

The present invention relates to an antibiotic bioadhesive material and a method of manufacturing the same, and more particularly to an antibiotic bioadhesive material composed of a substrate and a coating layer, the coating layer being fixed by a covalent bond On the surface of the substrate, the coating layer described above comprises a copolymer of a monomer having an epoxy group and a monomer having a diionic functional group. Secondly, the present invention also provides a method of producing the biomolecule-adhesive material.

In the field of materials, the bio-molecular adhesion properties of biomedical materials are an important issue. However, conventional techniques generally use a polymer such as polyethylene glycol (PEG) to temporarily impart a bio-molecular adhesion to the surface of a biomedical material by physical adsorption. However, due to the diversity of biomedical materials and the chemical inertness of the surface, the bio-adhesive effect of physical adsorption cannot meet the requirements of the industry and the stability is not good. Therefore, in the current field of biomedical materials, there is a lack of an anti-biomolecular adhesion technology that is highly efficient and can comprehensively modify various types of biomedical materials.

In summary, for the development of an anti-biomolecule adhesive material and a manufacturing method thereof, the original substrate used for the bio-molecular adhesive material is a variety of various materials and the manufacturing method can be comprehensively varied. The formation of an anti-molecular adhesive structure on the surface of the material is a technology that needs to be broken and has great potential. The above technology is especially applied in the field of novel biomedical materials. However, there is still a lack of relevant material design and technology in the current industrial technology field to overcome the problems faced by the current related industries.

In view of the above-mentioned background of the invention, in order to meet the requirements of the industry, one of the objects of the present invention is to provide an anti-biomolecular adhesive material, in particular to an anti-biomolecule composed of a substrate and a coating layer. a material, the coating layer is fixed on the surface of the substrate by a covalent bond, wherein the coating layer comprises a monomer having an epoxy group and a monomer having a diionic functional group. a copolymer. Secondly, the present invention also provides a method for producing the biomolecule-adhesive material.

A first object of the present invention is to provide an anti-biomolecular adhesive material comprising a substrate and a coating layer, the coating layer being fixed on the surface of the substrate by a covalent bond The coating layer comprises a copolymer of a monomer having an epoxy group and a monomer having a diionic functional group, and the copolymer has an average molecular weight of between 1 kDa and 3000 kDa.

In one embodiment, the above epoxy group-containing monomer comprises: glycidyl acrylate and glycidyl acrylate.

In one embodiment, the above-mentioned monomer having a diionic functional group comprises: a sulfobetaine alkyl acrylate, a sulfobetaine alkyl decyl amide, a carboxy betaine alkyl acrylate, a carboxy betaine alkyl group. Decylamine acrylate and phosphate betaine alkyl acrylate.

In a preferred embodiment, the copolymer has an average molecular weight of between 11 kDa and 30 kDa, and the copolymer can achieve a better bio-molecular adhesion.

In a preferred embodiment, the copolymer is a poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate) copolymer of polyglycidyl methacrylate and polyethyl sulfobetaine.

In a preferred embodiment, the above molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) is 0.15 to 1.35; In a more preferred embodiment, when the molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) is 0.2 to 0.3, the present invention Anti-biomolecular adhesive material has better anti-biomolecular adhesion effect.

A second object of the present invention is to provide a method for producing an anti-biomolecular adhesive material, comprising: providing a substrate; and performing an activation process to introduce a functional group on the surface of the substrate, the functional group comprising: a hydroxyl group, an amine group And a thiol group; providing a copolymer composed of a monomer having an epoxy group and a monomer having a diionic functional group, and the copolymer has an average molecular weight of from 1 kDa to 3000 kDa. And reacting to cause a covalent bond between the copolymer and the functional group on the surface of the substrate to form an anti-biomolecular adhesive material, wherein the reaction is at a pH of 1 to 5 or 8 to 11 Under the circumstances.

In one embodiment, the substrate comprises glass, metal, metal oxide, ceramic, germanium wafer, and plastic.

In one embodiment, the activation procedure described above includes a surface plasma treatment procedure, an ozone treatment procedure, a chemical modification procedure, and an ultraviolet irradiation procedure.

In one embodiment, the above epoxy group-containing monomer comprises: glycidyl acrylate and glycidyl acrylate.

In one embodiment, the monomer having a diionic functional group comprises: a sulfobetaine alkyl acrylate, a sulfobetaine alkyl decyl amide, a carboxy betaine alkyl acrylate, a carboxy betaine alkyl acrylate. Guanamine and phosphoric acid Ester betaine alkyl acrylate.

In a preferred embodiment, the copolymer has an average molecular weight of between 11 kDa and 30 kDa, and the copolymer can achieve a better anti-biomolecular adhesion effect.

In one embodiment, the copolymer is poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate), and the polymethyl group is poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate). The molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) is 0.15 to 1.35.

In a preferred embodiment, when the molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) is 0.2 to 0.3, The anti-biomolecular adhesive material of the invention has better anti-biomolecular adhesion effect.

In one embodiment, the pH 8-11 of the above reaction is adjusted by the addition of a tertiary amine comprising triethylamine.

In accordance with the above objects of the present invention, the present invention provides an anti-biomolecular adhesive material, and more particularly to a substrate and a coating layer. An antibiotic molecule adhering material, the coating layer being fixed on the surface of the substrate by a covalent bond, wherein the coating layer comprises a monomer having an epoxy group and a double ion functional group A copolymer composed of monomers polymerized. Secondly, the present invention also provides a method for producing the above-mentioned anti-biomolecular adhesive material, which comprises causing a covalent bond between an epoxy group of the coating layer and a surface of a substrate which generates a specific functional group via an activation process, The method is a bio-adhesive grafting method, which can form a double-ion structure interface in various kinds of diverse substrates, and thus has great potential for application to bio-molecular adhesion of various advanced materials, especially for biomedicine. Surface double ionization upgrading technology for materials.

The above and other technical contents, features and advantages of the present invention will be apparent from the following detailed description of the preferred embodiments. In order to thoroughly understand the present invention, detailed steps and compositions thereof will be set forth in the following description. Obviously, the practice of the invention is not limited to the specific details that are apparent to those skilled in the art. On the other hand, well-known components or steps are not described in detail to avoid unnecessarily limiting the invention. The preferred embodiments of the present invention are described in detail below, but the present invention may be widely practiced in other embodiments, and the scope of the present invention is not limited by the scope of the following patents. .

According to a first embodiment of the invention, the invention provides an antibiotic a molecular adhesive material comprising a substrate and a coating layer, the coating layer being fixed on the surface of the substrate by a covalent bond, wherein the coating layer comprises a ring A copolymer of a monomer of an oxy group and a monomer having a diionic functional group, and the copolymer has an average molecular weight of between 1 kDa and 3000 kDa.

In one embodiment, the anti-biomolecular adhesive material has a water contact angle of less than 30 degrees. Preferably, the anti-biomolecular adhesive material has a water contact angle of less than 10 degrees.

In one embodiment, the above epoxy group-containing monomer comprises glycidyl alkyl acrylate and glycidyl acrylate.

In one embodiment, the above-mentioned monomer having a diionic functional group comprises a sulfobetaine alkyl acrylate, a sulfobetaine alkyl decyl amide, a carboxy betaine alkyl acrylate, a carboxy betaine alkyl acrylate. Indoleamine and phosphate betaine alkyl acrylate.

In a preferred embodiment, the copolymer has an average molecular weight of between 11 kDa and 30 kDa, and the copolymer can achieve a better bio-molecular adhesion.

In a preferred embodiment, the copolymer is a copolymer of polyglycidyl methacrylate and polymethacryl sultaine (poly(glycidyl) Methacrylate)-co-poly(sulfobetainemethacrylate)).

In a preferred embodiment, the above molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) is 0.15 to 1.35; In a more preferred embodiment, when the molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) is 0.2 to 0.3, the present invention The anti-biomolecule adhesive material has better anti-biomolecular adhesion effect.

The above anti-biomolecular adhesive materials can be widely used in the field of medical equipment. In one embodiment, the medical device is a dental medical device, the substrate of the dental medical device is a metal or a metal oxide, and the copolymer of the anti-biomolecule coating layer is a polymethyl group. a copolymer of glycidyl acrylate and poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate), which is fixed to the above metal or metal oxide by covalent bonding And the molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) of the copolymer is 0.23±0.04, and the above The average molecular weight of the copolymer (poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate) is 24.9 kDa. According to the specific embodiment The dental medical device has a relative fibrinogen adsorption of less than 5%; while other non-inventive metal materials have a relative fibrinogen adsorption of greater than 20%. Accordingly, the biomolecule-adhesive material of the present invention has unpredictable effects compared to conventional techniques and related materials.

A second object of the present invention is to provide a method for producing an anti-biomolecular adhesive material, the method comprising the steps of: providing a substrate; performing an activation process to introduce a functional group on the surface of the substrate, the functional group comprising a hydroxyl group , an amine group and a thiol group; providing a copolymer composed of a monomer having an epoxy group and a monomer having a diionic functional group, and the above copolymer has an average molecular weight of 1 kDa Between ~3000kDa; and a reaction to cause the copolymer and the functional groups on the surface of the substrate to form a covalent bond to form an anti-biomolecular adhesive material, wherein the above reaction is at a pH of 1 to 5 or It is carried out under the environment of 8~11.

In one embodiment, the substrate comprises glass, metal, metal oxide, ceramic, germanium wafer, and plastic.

In one embodiment, the activation procedure described above includes a surface plasma treatment procedure, an ozone treatment procedure, a chemical modification procedure, and an ultraviolet irradiation procedure.

The purpose of the activation procedure described above is to introduce an official onto the surface of the substrate. An energy base, especially a substrate that is chemically inert on the surface, such as polytetrafluoroethylene or polystyrene. The activation procedure provided by the method of the invention can introduce different functional groups on the surface of the substrate.

In one embodiment, the surface of the substrate is introduced into the hydroxyl group by an ozone treatment procedure or an ultraviolet irradiation procedure.

In another embodiment, the surface of the substrate can be introduced into an amine group or a thiol group by a chemical modification procedure.

In one embodiment, the above epoxy group-containing monomer comprises: glycidyl acrylate and glycidyl acrylate.

In one embodiment, the monomer having a diionic functional group comprises: a sulfobetaine alkyl acrylate, a sulfobetaine alkyl decyl amide, a carboxy betaine alkyl acrylate, a carboxy betaine alkyl acrylate. Indoleamine and phosphate betaine alkyl acrylate.

In a preferred embodiment, the copolymer has an average molecular weight of between 11 kDa and 30 kDa, and the copolymer can achieve a better anti-biomolecular adhesion effect.

In one embodiment, the copolymer is a poly(glycidylmethacrylate)-co-poly(sulfobetainemethacrylate) copolymer of polyglycidyl methacrylate and poly(methacrylic acid) sulfobetaine. )), and the molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) is 0.15 to 1.35.

In a preferred embodiment, when the molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) is 0.2 to 0.3, The anti-biomolecular adhesive material of the invention has better anti-biomolecular adhesion effect.

In one embodiment, the pH 8-11 of the above reaction is adjusted by the addition of a tertiary amine comprising triethylamine.

In one embodiment, the method for producing the biomolecule-adhesive material described above is for producing anti-biomolecule-adhered polystyrene, and the method comprises the following steps: Providing a substrate made of polystyrene; producing a hydroxyl group on the surface of the substrate made of polystyrene by an ozone treatment program; providing a polyglycidyl methacrylate and a polymethyl group Poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate), and the poly(glycidyl methacrylate) and polymethyl Poly(sulfobetaine methacrylate) has a molar ratio of 0.23 and an average molecular weight of 24.9 kDa; and a ring opening reaction of an epoxy group under triethylamine as a catalyst to cause the above polymethylation A copolymer of glycidyl acrylate and poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate) and a polystyrene substrate having a hydroxyl group on the surface to form a covalent bond And made of a polystyrene material having anti-biomolecular adhesive properties.

The following examples are based on the experiments conducted in the above-described embodiments, and are based on the detailed description of the present invention.

Example 1: Synthesis of poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate), the above copolymer is represented by Gm-Sn, wherein m And n respectively represent the molar ratio of glycidyl methacrylate (GMA) and sulfobetaine methacrylate (SBMA) used in the preparation of the above copolymer, for example, G20-S80 indicates that the molar ratio of GMA to SBMA is 20:80.

The reaction equation for Example 1 is as follows:

Mix different molar ratios of GMA and SBMA in methanol and water and stir to form a 1M concentration of the reaction solution, then add the initiator AIBN (Azobisisobutyronitrile) under nitrogen and stir the temperature to 60 ° C for 6 hours. The reaction was quenched by the temperature of the bath and stirring was continued until a white solid precipitated. The above white solid was redissolved in water and purified with methanol, and finally lyophilized to give a white crystalline powder.

Table 1 shows the characteristics of poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate) copolymers synthesized by different molar ratios of GMA and SBMA; the average molecular weight (Mw) is determined by GPC (gel-permeation). Chromatography, and the synthesized copolymer (poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate)) poly(glycidylmethacrylate)/PGMA and polymethacrylic sulfobetaine The molar ratio (MA) of poly(sulfobetainemethacrylate)/PSBMA is estimated by the relative area ratio of characteristic peaks of different chemical shifts (δ) using hydrogen nuclear magnetic resonance spectroscopy (H ¹ -NMR in D2O). The hydrogen nuclear magnetic resonance spectrum is shown in Fig. 1, in which the epoxy (epoxide) in poly(glycidyl methacrylate) has a chemical shift (δ) of 2.9 and 3.6 in the hydrogen nuclear magnetic resonance spectrum. The position of ppm has two characteristic peaks; and the (CH ₃ ) ₂ N ⁺ in the diionic functional group in poly(sulfobetaine methacrylate) is in the above hydrogen nuclear magnetic resonance spectrum. The position of the chemical shift (δ) of 3.2 to 3.4 ppm has a characteristic peak.

^a The molar ratio was showed with the relative value between monomers and initiator. The mole of initiator was set as 1 mole compare to monomers. ^b Average molecular weight of the poly(GMA- co -SBMA) copolymers was estimated by gel permeable chromatography ( GPC) and calibrated with polyethyleneoxide (PEO). ^c Composition of the poly(GMA- co -SBMA) copolymers was estimated by ¹ H NMR in D ₂ O from the relative peak area of epoxidegroup of the PGMA in the range of δ at 2.9 and 3.6 Ppm and that of (CH ₃ ) ₂ N ⁺ proton resonance of the PSBMA side groups in the range of δ at 3.2 and 3.4 ppm.

Example 2: Preparation of an anti-biomolecular adhesive material comprising a poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate) coating layer of polyglycidyl methacrylate and poly(glycidyl methacrylate).

The substrates used in this example were germanium wafers, glass, titanium, stainless steel, and polystyrene. First, a hydroxyl group is introduced onto the surface of the substrate by ultraviolet irradiation or an ozone treatment procedure, and then the copolymer of the first example and the triethylamine are formulated into a coating aqueous solution, and then the substrate having the surface into which the hydroxyl group has been introduced is immersed. The above-mentioned aqueous coating solution is subjected to a reaction at 80 ° C for 24 hours, and then the substrate subjected to the graft reaction treatment is taken out. The substrate subjected to the graft reaction treatment is the anti-biomolecular adhesive material of the present invention.

The surface property analysis of the biomolecule-adhesive material prepared in Example 2: the surface property analysis of the bio-molecular-adhesive material of the present invention includes water contact angle measurement, X-ray photoelectron spectroscopy (XPS) surface structure analysis, Scanning electron microscopy analysis and copolymer (poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate) analysis on packing density of biomolecular adhesives.

The water contact angle was measured by a contact angle automatic measuring instrument (Model CA-VP, 209 Kyowa Interface Science Co., Ltd., Japan), and the procedure was as follows: A drop of 4 ul volume of water was placed in the prepared The biomolecule-adhesive material was measured at 25 ° C with a contact angle automatic measuring instrument. The resulting water contact angle measurement is taken at three different locations and the average is calculated. The water contact angle value curve of the biomolecule-adhesive material prepared by using the ruthenium wafer as the base material and different copolymers Gm-Sn is shown in Fig. 2.

X-ray photoelectron spectroscopy (XPS) analysis is used to analyze the surface structure of materials. Figure 3 is an XPS spectrum of an anti-biomolecular adhesive prepared by using the copolymer G20-S80 as a coating layer and an XPS spectrum of an untreated substrate. The copolymer is clearly seen by comparison. The anti-biomolecular adhesive material prepared by G20-S80 as a coating layer has a characteristic peak of N1s at a binding energy of about 402 eV, and has a characteristic peak of S2p at a binding energy of about 168 eV, thereby demonstrating that the copolymer G20- S80 is indeed immobilized on the surface of the substrate by covalent bonding.

Figure 4 is an anti-wear prepared by using the copolymer G20-S80 as a coating layer. The scanning electron micrograph of the biomolecular adhesive material and the scanning electron microscope image of the untreated substrate show that the anti-biomolecular adhesive material prepared by using the copolymer G20-S80 as a coating layer can be clearly seen by comparison. The surface structure is different from that of the untreated substrate surface, and the surface structure analysis result of FIG. 5 can be obtained by further calculation and analysis by the image processing software.

The packing density of poly(glycidyl methacrylate)-co-poly(sulfobetaine methacrylate) on biomolecular adhesives is measured by UV-vis absorption spectroscopy. The absorption peak of 220 nm was calculated to obtain the bulk density (ng/cm ² ) of the copolymer coated and fixed on the substrate.

Packing density = surface solute weight (ng) / unit area (cm ² )

In an example, when the copolymer G20-S80 is used as a coating layer and the triethylamine is used as a catalyst, the surface of the ruthenium, glass, titanium, stainless steel and polystyrene substrates after the activation process are respectively reacted. The relevant experimental analysis data of the anti-biomolecular materials prepared by the covalent bonding of the branches are shown in Table 2. It can be clearly seen from Table 2 that the water contact angle of the anti-biomolecular adhesive material of the present invention is compared with that of The untreated substrate was greatly reduced, and the relative fibrinogen adsorption percentage was significant. reduce.

The method for producing the biomolecule-adhesive material provided by the present invention can further optimize the effect of the prepared bio-molecular-adhesive material by adjusting the concentration of the copolymer and triethylamine in the reaction.

As shown in Fig. 6, when the concentration of the copolymer G20-S80 in the reaction conditions is 10 mg/ml and the concentration of triethylamine is 100 ul/ml, the biomolecule-adhering material produced can reach about 140 ng/cm. The surface coverage of ² is the packing density (ng/cm ² ) of the poly(glycidyl methacrylate)-co-poly (sulfobetaine methacrylate) on the biomolecule-adhesive material. At the same time, the anti-biomolecular adhesive material produced above has a percentage of adsorption relative to fibrinogen of less than 10%.

Anti-adhesion effect test of anti-biomolecular adhesive materials prepared by copolymer G20-S80 for various biomolecules

Example 3: Fibrinogen adsorption experiment

First, a biosensor having a surface plasmon resonance is prepared, which uses a displacement of a wavelength to measure a substance adsorption amount on a surface of the material, wherein when the displacement of the above wavelength is 1 nm, the surface of the material The amount of the substance to be tested (e.g., copolymer or protein) is about 15 ng/cm ² . Second, protein adhesion assays can also be performed using conventional techniques such as enzyme immunoassay (ELISA).

The experimental results are shown in Fig. 7. According to Fig. 7, when the concentration of the copolymer G20-S80 is 10 mg/ml and the concentration of triethylamine is 100 ul/ml, the copolymerization of the antibiotic biomolecule prepared by the above conditions is obtained. The surface coverage of the material G20-S80 on the substrate was 201 ng/cm ² , and the surface coverage of the fibrin element was only 0.13 ng/cm ² . Compared with the anti-biomolecular materials prepared without the process conditions of using triethylamine, the surface coverage of the copolymer G20-S80 on the substrate is only 92 ng/cm ² , and the surface coverage of the fibrin is higher. 5.54 ng/cm ² . Based on the above experimental data, it was specifically demonstrated that the use of triethylamine in the method for producing an anti-biomolecular material provided by the present invention can greatly reduce the adhesion of fibrinogen on the surface of the bio-molecular material and has an unpredictable effect.

Figure 8 is the experimental data of the relative fibrinogen adsorption percentage and water contact angle of the anti-biomolecular materials prepared under various substrate and reaction conditions with the copolymer G20-S80 as the coating layer. The figure demonstrates that the manufacturing method of the bio-molecular adhesive material using triethylamine as a catalyst is suitable for substrates of various materials.

Example 4: Blood cell sample attachment experiment

The blood cell sample attachment experiment is to put the test material into a 24-well culture dish, add 1% phosphate buffer (PBS) for 3 hours at 37 ° C, add the blood cell sample, and then incubate at 37 ° C for 2 hours. After taking out the above-mentioned materials to be tested, after cleaning and fixing procedures, the Confocal Laser Scanning Microscope (CLSM) is used to observe the adhesion of the blood cell sample on the surface of the material to be tested, and utilize The software quantifies the number of attachments of different hematocrit samples.

The experimental results are shown in Figure 9 and Table 3. When the copolymer G20-S80 is used as the coating layer and the triethylamine is used as the catalyst, respectively, the activated process of bismuth, glass, titanium, stainless steel and poly Materials prepared from styrene substrates have the lowest platelet and red blood cell attachment.

Example 5: Tissue Cell Attachment Experiment

The tissue cell attachment experiment was performed using human fibroblasts (HT-1080) as a test subject. After the test material was cultured with human fibroblasts (HT-1080) for 24 hours, the material to be tested was taken out, fixed, washed and labeled. The procedure then observes the attachment of human fibroblasts (HT-1080) on the material to be tested by a fluorescence microscope, and quantifies the attachment of tissue cells using the software.

The experimental results are shown in Fig. 10 and Table 4, when the copolymer G20-S80 is used as a coating layer, and under the conditions of triethylamine as a catalyst, respectively, after the activation process, bismuth, glass, titanium, stainless steel and poly Materials prepared from styrene substrates have the lowest amount of tissue cell attachment.

Example 6: Bacterial Attachment Experiment

The bacterial attachment experiment was carried out with E. coli as the test object. First, the culture of E. coli was carried out, and the concentration of the final bacterial solution was 10 ⁶ cells/mL. 1 ml of the bacterial solution was added and the material to be tested was placed. In the container, after 24 hours, the material to be tested was taken out, and after washing and staining procedures, the amount of E. coli attached was analyzed by a glory microscope.

The experimental results are shown in Fig. 11 and Table 5, when the copolymer G20-S80 is used as a coating layer, and under the conditions of triethylamine as a catalyst, respectively, after the activation process, bismuth, glass, titanium, stainless steel and poly The material prepared from the styrene substrate has the lowest E. coli attachment amount.

The above-mentioned experimental data of the anti-adhesive effects of various biomolecules were average data of 6 replicates, and the statistical analysis of variance (ANOVA) and student’s t-test were performed at the same time, and the confidence interval was 95%.

Practical application of medical equipment

The copolymer G20-S80 was used as a coating layer, and after grafting reaction with the mirror surface of the dental mirror after the activation procedure, the surface of the metal scalpel and the medical material made of polystyrene under the condition of triethylamine as a catalyst, respectively. The medical equipment was subjected to an E. coli and blood cell sample attachment experiment, and the results were as shown in Fig. 12 and Table 6. The medical equipment treated by the above conditions had an obvious effect of resisting biomolecules.

Figure 13 is a view showing the method for producing an anti-biomolecular adhesive material provided by the present invention, wherein the surface water contact angle of the anti-biomolecular adhesive material prepared under the condition that the reaction pH value is 1 to 5 or 8 to 11 It is greatly reduced to below 20 degrees and can reduce the relative adsorption amount of fibrinogen. It is thus proved that the method for producing the biomolecule-adhesive material provided by the present invention is resistant to biomolecules produced in a specific pH range. The material has unpredictable effects.

The present invention has been described by way of example only, and the scope of the invention is not to be construed as limited by the scope of the invention. In addition, the abstract sections and headings are only used to assist in the search of patent documents and are not intended to limit the scope of the invention.

Figure 1 shows a hydrogen nuclear magnetic resonance spectrum of a poly(glycidyl methacrylate)-co-poly (sulfobetaine methacrylate) of the present invention; and Fig. 2 shows an antibiotic bioadhesive material prepared by the copolymer Gm-Sn of the present invention. Water contact angle and relative fibrinogen adsorption% bar graph; Figure 3 shows the XPS spectrum of antibiotic bioadhesive material prepared by using the copolymer G20-S80 as coating layer And an XPS spectrum of the untreated substrate; Figure 4 shows a scanning electron micrograph of the biomolecule-adhesive material prepared as the coating layer of the copolymer G20-S80 of the present invention and an untreated substrate. Scanning electron micrograph; Figure 5 shows scanning electron micrograph and surface structure analysis of the biomolecule-adhesive material prepared by using the copolymer G20-S80 of the present invention as a coating layer; and Figure 6 shows the copolymer G20 of the present invention. -S80 concentration is 10mg/ml, and the concentration of triethylamine is 100ul/ml, the surface coverage of the biomolecule-adhesive material produced and the relative fibrinogen adsorption percentage (relative fibrinogen adsorptio) n%) bar graph; Figure 7 shows the surface coverage of the biomolecule-adhesive material produced when the concentration of the copolymer G20-S80 of the present invention is 10 mg/ml and the concentration of triethylamine is 100 ul/ml. Relative fibrinogen adsorption amount versus treatment time curve Figure 8 is a bar graph showing the relative fibrinogen adsorption percentage and water contact angle of the anti-biomolecular material prepared by using the copolymer G20-S80 as a coating layer of the present invention; and Figure 9 shows the copolymer of the present invention. G20-S80 is a laser conjugated-focus laser scanning electron microscope image and a quantitative bar graph of a blood cell attachment experiment of an anti-biomolecular material prepared as a coating layer; and FIG. 10 shows a copolymer G20-S80 of the present invention. Fluorescence micrograph and quantified bar graph of tissue cell attachment experiment of anti-biomolecular material prepared as coating layer; Figure 11 shows anti-biomolecule prepared by using copolymer G20-S80 as coating layer of the present invention Fluorescence micrograph and quantitative bar graph of the bacterial attachment experiment of the material; Fig. 12 shows the anti-biomolecular adhesion image and quantified length of the medical device prepared by using the copolymer G20-S80 as the coating layer of the present invention Bar graph; and Fig. 13 show the water contact angle and relative fibrinogen adsorption percentage of the anti-biomolecular adhesive material produced by the method for producing the bio-molecular-adhesive material of the present invention in different pH ranges (relative fibrin) Og adsorption%) Bar graph.

Claims (16)

An anti-biomolecular adhesive material consisting of a substrate and a coating layer, the substrate being treated by a surface plasma treatment process, an ozone treatment program, a chemical modification program or ultraviolet rays The irradiation program introduces a functional group on the surface of the substrate, the functional group comprising: a hydroxyl group, an amine group and a thiol group, the coating layer being fixed on the surface of the substrate by a covalent bond, wherein the coating layer is A copolymer comprising a monomer having an epoxy group and a monomer having a diionic functional group, and the copolymer has an average molecular weight of between 11 and 30 kDa. For example, in the anti-biomolecular adhesive material of claim 1, the water contact angle of the antibiotic bioadhesive material is less than 30 degrees. For example, in the anti-biomolecular adhesive material of claim 1, the substrate comprises glass, metal, metal oxide, ceramic, germanium wafer and plastic. The anti-biomolecular adhesive material according to claim 1, wherein the monomer having an epoxy group comprises glycidyl acrylate and glycidyl acrylate. The anti-biomolecular adhesive material according to claim 1, wherein the monomer having a diionic functional group comprises: a sulfobetaine alkyl acrylate, a sulfobetaine alkyl decyl amide, a carboxy betaine. Alkyl acrylate, carboxybetaine alkyl decyl amide and phosphate betaine alkyl acrylate. The anti-biomolecular adhesive material according to claim 1, wherein the copolymer is poly(glycidyl methacrylate)-co-poly of polyglycidyl methacrylate and polymethacrylic sulfobetaine. (sulfobetaine methacrylate)). For example, in the anti-biomolecular adhesive material of claim 7, wherein the above poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) are not The ear ratio is 0.15~1.35. For example, in the anti-biomolecular adhesive material of claim 8, wherein the above-mentioned polyglycidyl methacrylate and polymethacrylic sulfobetaine have a molar ratio of 0.2 to 0.3. A method for producing an anti-biomolecular adhesive material, comprising: (1) providing a substrate; (2) performing an activation process to introduce a functional group on the surface of the substrate, The functional group comprises: a hydroxyl group, an amine group and a thiol group; (3) providing a copolymer composed of a monomer having an epoxy group and a monomer having a diionic functional group. And the average molecular weight of the copolymer is between 11 and 30 kDa; and (4) performing a reaction to cause the copolymer and the functional groups on the surface of the substrate to form a covalent bond to form an anti-biomolecular adhesive material. The above reaction is carried out in a pH of 1 to 5 or 8 to 11. The method for producing an antibiotic bioadhesive material according to claim 9, wherein the substrate comprises glass, metal, metal oxide, ceramic, germanium wafer and plastic. The method for producing an anti-biomolecular adhesive material according to claim 9 , wherein the activation procedure comprises: a surface plasma treatment program, an ozone treatment program, a chemical modification program, and an ultraviolet irradiation program. The method for producing an anti-biomolecular adhesive material according to claim 9, wherein the monomer having an epoxy group comprises glycidyl acrylate and glycidyl acrylate. The method for producing an anti-biomolecular adhesive material according to claim 9, wherein the monomer having a diionic functional group comprises a sulfobetaine alkyl acrylate, a sulfobetaine alkyl decyl amide, a carboxyl group. Betaine alkyl acrylate, carboxybetaine alkyl decyl amide and phosphate betaine alkyl acrylate. The method for producing an antibiotic bioadhesive material according to claim 9, wherein the copolymer is a poly(glycidylmethacrylate)-copolymer of polyglycidyl methacrylate and polymethacryl sultaine. -poly(sulfobetaine methacrylate), and the molar ratio of poly(glycidyl methacrylate) and poly(sulfobetaine methacrylate) is 0.15 to 1.35. The method for producing an anti-biomolecular adhesive material according to claim 14, wherein the polyglycidyl methacrylate and the polymethacrylic sulfobetaine have a molar ratio of 0.2 to 0.3. The method for producing an anti-biomolecular adhesive material according to claim 9, wherein the above-mentioned pH values 8 to 11 are adjusted by adding a tertiary amine, and the tertiary amine comprises triethylamine.