Antibacterial composition, antibacterial coating, forming method of antibacterial coating and medical instrument

Abstract

The invention provides an antibacterial composition, an antibacterial coating, a forming method of the antibacterial coating and a medical device. In the invention, the flavonoid compound specifically comprises baicalein and / or quercetin. The antibacterial coating is prepared from the antibacterial composition, on one hand, the polyglutamic acid has natural antibacterial performance and can effectively kill bacteria in contact with the coating; on the other hand, as an important signal molecule in the bacterial biofilm, the flavonoid compound can inhibit the formation of the bacterial biofilm and induce the dispersion of the mature bacterial biofilm, so that the biofilm on the surface of the medical instrument is effectively removed. Meanwhile, the main components of the antibacterial coating are all natural products, so that the antibacterial coating has good biocompatibility and is not easy to cause immunological rejection of a human body.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical materials, and particularly relates to an antibacterial composition, an antibacterial coating, a method for forming an antibacterial coating, and a medical device. Background Art

[0002] During the use of medical devices, exogenous bacteria are likely to adhere and form a bacterial biofilm that is difficult to remove, thereby causing serious infections. To solve this problem, a medical coating is generally formed on the surface of medical devices at present to effectively prevent the adhesion of bacteria on the surface of medical devices and the formation of biofilms.

[0003] It can be seen that excellent antibacterial properties and the prevention of the formation of bacterial biofilms are the key features for such medical coatings to function, specifically referring to: 1) killing bacteria in contact with the coating; 2) removing biofilms formed by other bacteria that have not been killed on the surface. Among them, killing bacteria in contact with the coating can effectively prevent their further adhesion and ensure the safety of medical devices during use. At the same time, once bacteria escape the antibacterial effect of the coating, the coating can prevent bacteria from further forming biofilms and remove the already formed biofilms, thereby extending the service life of medical devices.

[0004] However, at present, due to the lack of antibacterial biofilm medical coatings with biocompatibility and biodegradability, the clinical transformation is limited. Therefore, developing antibacterial biofilm coatings with biodegradability, excellent biocompatibility, and excellent antibacterial and bactericidal properties is a common demand in practical applications. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide an antibacterial composition, an antibacterial coating, a method for forming an antibacterial coating, and a medical device. The antibacterial coating has effective bactericidal, biofilm formation inhibition, and biofilm removal capabilities, and can effectively improve the hygiene and safety of medical devices.

[0006] To achieve this purpose, the present invention adopts the following technical solutions:

[0007] In the first aspect, the present invention provides an antibacterial composition, which includes flavonoid compounds and polyglutamic acid;

[0008] The flavonoid compounds include baicalein and / or quercetin, and general commercially available products can be used.

[0009] Preferably, the ratio of the flavonoid compounds to polyglutamic acid is 1 g:(0.1 - 1) g.

[0010] Preferably, the molecular weight of the polyglutamic acid is 200 - 500 kDa.

[0011] In a second aspect, the present invention provides an antibacterial coating formed from the above antibacterial composition.

[0012] In a third aspect, the present invention provides a method for forming the above antibacterial coating, comprising the following steps:

[0013] S1: Immerse a substrate material with reactive functional groups on its surface in a flavonoid compound solution, and after reaction, obtain a substrate material with flavonoid compounds modified on its surface;

[0014] The reactive functional groups are hydroxyl groups and / or peroxyhydroxyl groups;

[0015] S2: Immerse the substrate material with flavonoid compounds modified on its surface in a polyglutamic acid alkaline solution, and after reaction, obtain an antibacterial coating formed on the substrate material.

[0016] Preferably, the substrate material with reactive functional groups on its surface is obtained by subjecting the substrate material to plasma treatment.

[0017] Preferably, the atmosphere of the plasma treatment is oxygen, the time is 3 - 10 min, and the power is 50 - 150 W.

[0018] Preferably, the substrate material includes any one or more of polyolefin medical materials, polyurethane medical materials, or silicone medical materials.

[0019] Preferably, the shape of the substrate material includes sheet and tubular.

[0020] Preferably, the solvent of the flavonoid compound solution is water, and the mass concentration of the flavonoid compound solution is 2 - 10 mg / mL.

[0021] Preferably, the ratio of the substrate material with reactive functional groups on its surface to the flavonoid compound solution is 1 g : (100 - 200) mL.

[0022] Preferably, the ratio of the substrate material with flavonoid compounds modified on its surface to the polyglutamic acid alkaline solution is 1 g : (100 - 200) mL.

[0023] Preferably, the mass concentration of the polyglutamic acid alkaline solution is 0.1 - 5 mg / mL, and the pH is 8 - 9.

[0024] Preferably, the temperature of the reaction in step S1 is 15 - 30 °C, and the time is 0.5 - 12 h.

[0025] Preferably, the temperature of the reaction in step S2 is 15 - 30 °C, and the time is 12 - 36 h.

[0026] Preferably, the reactions in steps S1 and S2 are both carried out under shaking conditions, and the rotation speed of the shaking is 200 - 300 r / min.

[0027] Fourthly, the present invention provides a medical material, which comprises a medical material matrix and an antibacterial coating formed on the surface of the medical material matrix.

[0028] Preferably, the thickness of the antibacterial coating is 50 - 200 μm.

[0029] Preferably, the medical material matrix is selected from any one or more of polyolefin medical materials, polyurethane medical materials or silicone medical materials.

[0030] Preferably, the medical material is a medical device.

[0031] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0032] The present invention provides an antibacterial composition comprising flavonoids and polyglutamic acid. In the present invention, the flavonoids specifically include baicalein and / or quercetin, which are lower in cost than other flavonoids, and have more stable physiological effects, anti-inflammatory and antioxidant effects. The present invention prepares the above antibacterial composition into an antibacterial coating. On the one hand, polyglutamic acid has natural antibacterial properties and can effectively kill bacteria contacting the coating. On the other hand, flavonoids, as important signal molecules in bacterial biofilms, can inhibit the formation of bacterial biofilms and induce the dispersion of mature bacterial biofilms, effectively removing the biofilms on the surface of medical devices. At the same time, the main components of the antibacterial coating are all natural products, having good biocompatibility and biodegradability, and are not likely to cause immune rejection reactions in the human body.

[0033] The present invention also provides a method for forming an antibacterial coating. In this method, flavonoids are modified on the surface of a substrate material through various non-covalent interactions, and then through an oligomerization reaction, polyglutamic acid is deposited on the surface of the substrate material, and the two are stably complexed, so that they are not likely to fall off and fail during use.

[0034] Taking the polyurethane material coated with the antibacterial coating of the present invention as an example, through testing, it is found that the antibacterial coating has excellent antibacterial and bactericidal properties, and still has excellent bactericidal properties after being placed for 7 days. It can be seen that the antibacterial and bactericidal ability of the antibacterial coating is persistent. Detailed embodiments

[0035] Next, in combination with the embodiments of the present invention, the technical solutions of the present invention will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0036] The present invention provides an antibacterial composition, which includes flavonoids and polyglutamic acid, and the ratio of the flavonoids to polyglutamic acid is 1 g:(0.1 - 1) g. For example, it can be 1 g:0.1 g, 1 g:0.2 g, 1 g:0.3 g, 1 g:0.4 g, 1 g:0.5 g, 1 g:0.6 g, 1 g:0.7 g, 1 g:0.8 g, 1 g:0.9 g, 1 g:1 g.

[0037] In the present invention, the flavonoids can inhibit the formation of bacterial biofilms and induce the dispersion of mature bacterial biofilms, effectively removing the biofilms on the surface of medical devices.

[0038] In the present invention, rotenone, isocoumarin, baicalein, and quercetin are used as flavonoids for experimental exploration and comparison. The results show that when rotenone and / or isocoumarin are used as flavonoids, compared with using baicalein and / or quercetin as flavonoids, the antibacterial and anti-biofilm effects of the final product will be reduced. Therefore, the present invention preferably uses baicalein and / or quercetin as flavonoids. At the same time, baicalein and / or quercetin are inexpensive and have simple structures, which are convenient for use.

[0039] Therefore, the present invention preferably includes that the flavonoids include baicalein and / or quercetin. Among them, baicalein has the structure shown in Formula 1, and quercetin has the structure shown in Formula 2:

[0040]

[0041] In the present invention, the polyglutamic acid has antibacterial properties, and its molecular weight is preferably 200 - 500 kDa. For example, it can be 200 kDa, 250 kDa, 300 kDa, 350 kDa, 400 kDa, 450 kDa, or 500 kDa, etc., and is preferably 350 kDa. The present invention has no special restrictions on the source of polyglutamic acid, and general commercially available products can be used.

[0042] The present invention also provides an antibacterial coating formed by the above antibacterial composition.

[0043] In some embodiments of the invention, the antibacterial coating has an anti-biofilm function, and its thickness is 50 - 200 μm.

[0044] Since the present invention uses flavonoids and polyglutamic acid as the main components of the antibacterial composition, both of which are natural products and have good biocompatibility, therefore, as an antibacterial coating on the surface of medical materials (such as medical devices), it is not likely to cause immune rejection reactions in the human body.

[0045] The present invention also provides a method for forming the above antibacterial coating, comprising the following steps:

[0046] S1: Immerse the substrate material with active reactive groups on its surface in a flavonoid compound solution, and after reaction, obtain a substrate material with flavonoids modified on its surface;

[0047] S2: Immerse the substrate material with flavonoids modified on its surface in a polyglutamic acid alkaline solution, and after reaction, obtain an antibacterial coating formed on the substrate material.

[0048] According to the present invention, a substrate material with active reactive groups on its surface is first provided.

[0049] In the present invention, the substrate material with active reactive groups on its surface is obtained by subjecting the substrate material to plasma treatment. Among them, the atmosphere of the plasma treatment is preferably oxygen, the time is 3 to 10 minutes, preferably 5 to 8 minutes; the power is 50 to 150 W, preferably 100 W. In the present invention, after plasma treatment in an oxygen atmosphere, the surface of the substrate material will carry active groups such as hydroxyl groups and / or peroxyhydroxyl groups, which can subsequently undergo non-covalent interactions with the substrate material and thus be modified on the surface of the substrate material.

[0050] In the present invention, the substrate material includes any one or more of polyolefin medical materials, polyurethane medical materials, or silicone medical materials. The shape of the substrate material can be designed as needed and can include sheets and tubes. The present invention does not particularly limit the source of the above substrate materials, and general commercially available products can be used. In a certain embodiment of the present invention, the substrate material is a thermoplastic polyurethane film.

[0051] In some embodiments of the present invention, the substrate material with active reactive groups on its surface is prepared according to the following method:

[0052] Cut the substrate material into an appropriate size, wash it with ultrapure water and dry it, place it in the treatment chamber of a plasma cleaner, turn on the machine vacuum, and after the vacuum degree of the treatment chamber reaches the standard, use oxygen as the treatment atmosphere, adjust the radio frequency to 50 to 150 W, and treat for 3 to 10 minutes.

[0053] After obtaining the substrate material with reactive functional groups on its surface, according to the present invention, it is immersed in a flavonoid compound solution, so that the flavonoid compound undergoes non-covalent interaction with the substrate material, thereby obtaining a substrate material with flavonoid compound modified on its surface.

[0054] In the present invention, the solvent of the flavonoid compound solution is water, and the mass concentration of the flavonoid compound solution is 2 - 10 mg / mL, preferably 5 mg / mL. Specifically, the preparation method of the flavonoid compound solution includes: blending the flavonoid compound with ultrapure water, and stirring at a stirring rate of 200 - 300 r / min at 30 - 50 °C until completely dissolved, preferably at 40 °C and a stirring rate of 270 r / min until completely dissolved.

[0055] In the present invention, after the substrate material with reactive functional groups on its surface is immersed in the flavonoid compound solution, it is preferably reacted under shaking conditions. The reaction temperature is room temperature, specifically 15 - 30 °C, preferably 20 - 25 °C; the rotation speed is 200 - 300 r / min, preferably 270 r / min. Among them, the immersion time is 0.5 - 12 h, preferably 2 - 10 h, more preferably 5 - 8 h.

[0056] In the present invention, the ratio of the substrate material with reactive functional groups on its surface to the flavonoid compound solution is 1 g : (100 - 200) mL, preferably 1 g : (120 - 160) mL.

[0057] In the present invention, after the reaction between the substrate material with reactive functional groups on its surface and the flavonoid compound solution ends, it is preferably taken out, washed and dried to obtain a substrate material with flavonoid compound modified on its surface. The washing can be carried out with clear water, preferably with ultrapure water.

[0058] Then, according to the present invention, the substrate material with flavonoid compound modified on its surface is immersed in a polyglutamic acid alkaline solution. The catechol structure of the flavonoid compound will be oxidized to a quinone structure, and the quinone can undergo a Michael addition reaction with the nucleophilic side chain of polyglutamic acid to form a covalent bond, so as to deposit polyglutamic acid on the surface of the substrate material. At the same time, the flavonoid compound can undergo oligomerization under alkaline conditions, and the flavonoid molecules are connected to each other, and finally an antibacterial coating formed on the substrate material is obtained. In some embodiments of the present invention, the ratio of the substrate material with flavonoid compound modified on its surface to the polyglutamic acid alkaline solution is 1 g : (100 - 200) mL, preferably 1 g : (120 - 180) mL.

[0059] In the present invention, the molecular weight of the polyglutamic acid is 200 - 500 kDa; preferably 350 kDa; the mass concentration of the polyglutamic acid alkaline solution is 0.1 - 5 mg / mL, preferably 2 - 4 mg / mL, more preferably 3 mg / mL; the pH of the polyglutamic acid solution is 8 - 9, preferably 8.5.

[0060] In the present invention, the temperature of the oligomerization reaction is room temperature, specifically 15 - 30 °C, and the reaction time is 12 - 36 h; preferably 25 °C, 24 h. The oligomerization reaction is preferably carried out under shaking conditions, with a rotation speed of 200 - 300 r / min, preferably 270 r / min.

[0061] In the present invention, after the reaction between the substrate material surface - modified with flavonoids and the polyglutamic acid alkaline solution, it is preferred to take out the substrate material, wash and dry it to obtain the substrate material with flavonoids surface - modified. The washing can be carried out with clear water, and preferably with ultrapure water.

[0062] It can be seen that the method for forming the above - mentioned antibacterial coating provided by the present invention is simple and convenient, easy to implement, and conducive to large - scale or industrial production.

[0063] The present invention also provides a medical material, which includes a medical material matrix and an antibacterial coating formed on the surface of the medical material matrix;

[0064] The antibacterial coating is the antibacterial coating involved in the above - mentioned technical solution.

[0065] In the present invention, the thickness of the antibacterial coating is 50 - 200 μm, such as 50 μm, 80 μm, 100 μm, 120 μm, 150 μm, 180 μm or 200 μm, etc.; the medical material matrix is selected from any one or more of polyolefin medical materials, polyurethane medical materials or silicone medical materials; the medical material can specifically be a medical device.

[0066] In summary, compared with the prior art, the present invention provides a preparation method of a flavonoid - assisted polyglutamic acid antibacterial biofilm medical coating, including: A) subjecting the substrate material that needs to be modified with a medical coating to surface plasma treatment to make its surface carry active reaction groups; B) immersing the substrate material with active reaction groups on its surface in a flavonoid solution so that the flavonoids and the substrate material undergo non - covalent interactions to obtain a substrate material surface - modified with flavonoids; C) immersing the substrate material surface - modified with flavonoids in a polyglutamic acid alkaline solution so that the flavonoids undergo an oligomerization reaction to obtain an antibacterial biofilm medical coating. The present invention deposits polyglutamic acid on the surface of the target substrate material through the oligomerization reaction of flavonoids under alkaline conditions, thereby forming an antibacterial biofilm medical coating.

[0067] The specific beneficial technical effects of the present invention include:

[0068] (1) The antibacterial biofilm medical coating of the present invention has polyglutamic acid and flavonoids as main components, wherein polyglutamic acid has natural antibacterial properties and can effectively kill bacteria that contact the coating; on the other hand, flavonoids are important signal molecules in bacterial biofilms, which can inhibit the formation of bacterial biofilms and induce the dispersion of mature bacterial biofilms, effectively removing biofilms on the surface of medical devices;

[0069] (2) The flavonoid compounds of the present invention are modified on the surface of the substrate material through a variety of non-covalent interactions, and then the polyglutamic acid is deposited on the surface of the substrate material through an oligomerization reaction. The two are stably complexed and are not easily detached and ineffective during use;

[0070] (3) The main components of the polyglutamic acid coating of the present invention are all natural products, have good biocompatibility, and are not likely to cause immune rejection reactions in the human body.

[0071] To further illustrate the present invention, the following examples are used for detailed description. The substrate material used in the following examples of the present invention is a thermoplastic polyurethane film; polyglutamic acid (Mw=350 kDa) was purchased from Nanjing Xuankai Biotechnology Co., Ltd.; rotenone was purchased from Aladdin, model R105076; isoliquiritigenin was purchased from Aladdin, model I111284; Baicalin was purchased from Sichuan Jingcui Tiancheng Pharmaceutical Co., Ltd., model TC0709; quercetin was purchased from Aladdin, model Q111274.

[0072] Example 1

[0073] (1) Plasma treatment of the substrate material, specifically comprising the following steps: cutting the thermoplastic polyurethane film into a suitable size, washing it with ultrapure water and drying it, placing it in a treatment chamber of a plasma cleaning machine, turning on the vacuum of the machine, and after the vacuum degree of the treatment chamber reaches the standard, using oxygen as the treatment atmosphere, adjusting the radio frequency to 100 W, and treating for 6 minutes;

[0074] (2) adding quercetin to 40°C water and stirring at 270 r / min for 24 h, wherein the mass concentration of quercetin is 5 mg / mL;

[0075] (3) placing the thermoplastic polyurethane film substrate obtained in step (1) in the quercetin solution obtained in step (2), wherein the volume ratio of the thermoplastic polyurethane film substrate to the quercetin solution is 1 g:150 mL, and soaking for 8 hours;

[0076] (4) taking out the thermoplastic polyurethane film substrate after the reaction (i.e., the thermoplastic polyurethane film substrate with quercetin surface modified thereon), washing it with ultrapure water and drying it;

[0077] (5) Prepare an alkaline solution of polyglutamic acid, which specifically includes the following steps: Dissolve polyglutamic acid in water with a mass concentration of 3 mg / mL, and adjust its pH to 8.5 with an aqueous sodium hydroxide solution;

[0078] (6) Place the thermoplastic polyurethane film substrate modified with quercetin obtained in step (4) into the alkaline solution of polyglutamic acid obtained in step (5), where the volume ratio of the thermoplastic polyurethane film substrate modified with quercetin to the polyglutamic acid solution is 1 g:150 mL, shake at a rate of 270 r / min, and react at 25 °C for 24 h.

[0079] Example 2

[0080] (1) Plasma-treat the substrate material, which specifically includes the following steps: Cut the thermoplastic polyurethane film into appropriate sizes, wash and dry it with ultrapure water, place it in the treatment chamber of the plasma cleaner, turn on the machine vacuum, and when the vacuum degree of the treatment chamber reaches the standard, use oxygen as the treatment atmosphere, adjust the radio frequency to 95 W, and treat for 7 min;

[0081] (2) Add baicalein to water at 40 °C and stir at a speed of 270 r / min for 20 h, where the mass concentration of quercetin is 4 mg / mL;

[0082] (3) Place the thermoplastic polyurethane film substrate obtained in step (1) into the quercetin solution obtained in step (2), where the volume ratio of the thermoplastic polyurethane film substrate to the baicalein solution is 1 g:150 mL, and soak for 6 h.

[0083] (4) Take out the reacted thermoplastic polyurethane film substrate (i.e., the thermoplastic polyurethane film substrate modified with baicalein), wash it with ultrapure water and dry it;

[0084] (5) Prepare an alkaline solution of polyglutamic acid, which specifically includes the following steps: Dissolve polyglutamic acid in water with a mass concentration of 5 mg / mL, and adjust its pH to 8.5 with an aqueous sodium hydroxide solution;

[0085] (6) Place the thermoplastic polyurethane film substrate modified with baicalein obtained in step (4) into the alkaline solution of polyglutamic acid obtained in step (5), where the volume ratio of the thermoplastic polyurethane film substrate modified with baicalein to the polyglutamic acid solution is 1 g:150 mL, shake at a rate of 270 r / min, and react at 25 °C for 24 h.

[0086] Example 3

[0087] (1) Treat the substrate material with plasma, specifically including the following steps: Cut the thermoplastic polyurethane film into an appropriate size, wash it with ultrapure water and dry it, place it in the treatment chamber of the plasma cleaner, turn on the machine vacuum, and after the vacuum degree of the treatment chamber reaches the standard, use oxygen as the treatment atmosphere, adjust the radio frequency to 110 W, and treat for 7 min to obtain a thermoplastic polyurethane film substrate;

[0088] (2) Add quercetin to water at 40 °C and stir at a speed of 270 r / min for 24 h to dissolve it, where the mass concentration of quercetin is 6 mg / mL;

[0089] (3) Place the thermoplastic polyurethane film substrate obtained in step (1) in the quercetin solution obtained in step (2), where the volume ratio of the thermoplastic polyurethane film substrate to the quercetin solution is 1 g:140 mL, and soak for 8 h;

[0090] (4) Take out the reacted thermoplastic polyurethane film substrate (i.e., the thermoplastic polyurethane film substrate surface-modified with baicalein), wash it with ultrapure water and dry it;

[0091] (5) Prepare a polyglutamic acid alkaline solution, specifically including the following steps: Dissolve polyglutamic acid in water, the mass concentration of polyglutamic acid is 7 mg / mL, and adjust its pH to 8.5 with an aqueous sodium hydroxide solution;

[0092] (6) Place the thermoplastic polyurethane film substrate surface-modified with quercetin obtained in step (4) into the polyglutamic acid alkaline solution obtained in step (5), where the volume ratio of the thermoplastic polyurethane film substrate to the polyglutamic acid solution is 1 g:140 mL, shake at a rate of 270 r / min, and react at 25 °C for 24 h.

[0093] Comparative Example 1

[0094] (1) Treat the substrate material with plasma, specifically including the following steps: Cut the thermoplastic polyurethane film into an appropriate size, wash it with ultrapure water and dry it, place it in the treatment chamber of the plasma cleaner, turn on the machine vacuum, and after the vacuum degree of the treatment chamber reaches the standard, use oxygen as the treatment atmosphere, adjust the radio frequency to 100 W, and treat for 6 min to obtain a thermoplastic polyurethane film substrate;

[0095] (2) Prepare a polyglutamic acid alkaline solution, specifically including the following steps: Dissolve polyglutamic acid in water, the mass concentration of polyglutamic acid is 3 mg / mL, and adjust its pH to 8.5 with an aqueous sodium hydroxide solution;

[0096] (3) Place the thermoplastic polyurethane film substrate obtained in step (1) into the polyglutamic acid alkaline solution obtained in step (2), where the volume ratio of the thermoplastic polyurethane film substrate to the polyglutamic acid solution is 1 g:150 mL, shake at a rate of 270 r / min, and react at 25 °C for 24 h.

[0097] Comparative Example 2

[0098] (1) Quercetin was added to water at 40 °C and stirred at a speed of 270 r / min for 24 h to dissolve, where the mass concentration of quercetin was 5 mg / mL;

[0099] (2) The thermoplastic polyurethane film substrate was placed in the quercetin solution obtained in step (1), where the volume ratio of the thermoplastic polyurethane film substrate to the quercetin solution was 1 g:150 mL, and soaked for 8 h;

[0100] (3) The reacted thermoplastic polyurethane film substrate was taken out, washed with ultrapure water and dried.

[0101] (4) To prepare an alkaline solution of polyglutamic acid, the following steps were specifically included: polyglutamic acid was dissolved in water, the mass concentration of polyglutamic acid was 3 mg / mL, and its pH was adjusted to 8.5 with an aqueous sodium hydroxide solution.

[0102] (5) The surface-modified quercetin thermoplastic polyurethane film substrate obtained in step (3) was put into the alkaline polyglutamic acid solution obtained in step (5), where the volume ratio of the surface-modified quercetin thermoplastic polyurethane film substrate to the polyglutamic acid solution was 1:150, shaken at a rate of 270 r / min, and reacted at 25 °C for 24 h.

[0103] Comparative Example 3

[0104] (1) Plasma treatment of the substrate material, specifically including the following steps: The thermoplastic polyurethane film was cut into a suitable size, washed and dried with ultrapure water, placed in the treatment chamber of the plasma cleaner, the machine vacuum was turned on, and after the vacuum degree of the treatment chamber reached the standard, oxygen was used as the treatment atmosphere, the radio frequency was adjusted to 100 W, and treated for 6 min;

[0105] (2) Rotenone was added to water at 40 °C and stirred at a speed of 270 r / min for 24 h to dissolve, where the mass concentration of rotenone was 5 mg / mL;

[0106] (3) The thermoplastic polyurethane film substrate obtained in step (1) was placed in the rotenone solution obtained in step (2), where the volume ratio of the thermoplastic polyurethane film substrate to the quercetin solution was 1 g:150 mL, and soaked for 8 h;

[0107] (4) The reacted thermoplastic polyurethane film substrate (i.e., the surface-modified rotenone thermoplastic polyurethane film substrate) was taken out, washed with ultrapure water and dried;

[0108] (5) Prepare an alkaline solution of polyglutamic acid, which specifically includes the following steps: Dissolve polyglutamic acid in water with a mass concentration of 3 mg / mL, and adjust its pH to 8.5 with an aqueous sodium hydroxide solution;

[0109] (6) Put the thermoplastic polyurethane film substrate modified with rotenone obtained in step (4) into the alkaline polyglutamic acid solution obtained in step (5), where the volume ratio of the thermoplastic polyurethane film substrate modified with rotenone to the polyglutamic acid solution is 1 g:150 mL, shake at a rate of 270 r / min, and react at 25 °C for 24 h.

[0110] Comparative Example 4

[0111] (1) Plasma-treat the substrate material, which specifically includes the following steps: Cut the thermoplastic polyurethane film into appropriate sizes, wash and dry it with ultrapure water, put it into the processing chamber of the plasma cleaner, turn on the machine vacuum, and when the vacuum degree of the processing chamber reaches the standard, use oxygen as the processing atmosphere, adjust the radio frequency to 100 W, and process for 6 min;

[0112] (2) Add isoliquiritigenin to water at 40 °C and stir at a speed of 270 r / min for 24 h, where the mass concentration of isoliquiritigenin is 5 mg / mL;

[0113] (3) Place the thermoplastic polyurethane film substrate obtained in step (1) into the isoliquiritigenin solution obtained in step (2), where the volume ratio of the thermoplastic polyurethane film substrate to the isoliquiritigenin solution is 1 g:150 mL, and soak for 8 h;

[0114] (4) Take out the reacted thermoplastic polyurethane film substrate (i.e., the thermoplastic polyurethane film substrate modified with quercetin), wash it with ultrapure water and dry it;

[0115] (5) Prepare an alkaline solution of polyglutamic acid, which specifically includes the following steps: Dissolve polyglutamic acid in water with a mass concentration of 3 mg / mL, and adjust its pH to 8.5 with an aqueous sodium hydroxide solution;

[0116] (6) Put the thermoplastic polyurethane film substrate modified with isoliquiritigenin obtained in step (4) into the alkaline polyglutamic acid solution obtained in step (5), where the volume ratio of the thermoplastic polyurethane film substrate modified with isoliquiritigenin to the polyglutamic acid solution is 1 g:150 mL, shake at a rate of 270 r / min, and react at 25 °C for 24 h.

[0117] Antibacterial performance test

[0118] Take 0.1 mL with a concentration of 1×10 8The Staphylococcus aureus suspension at CFU / mL was evenly coated on an agar culture plate, and then the polyurethane films with coatings obtained in the examples and comparative examples (circular, with a diameter of 2 cm) were gently placed thereon, and co-cultured in an incubator at 37 °C for 24 h. After taking out, the diameter of the antibacterial ring under the polyurethane film was measured.

[0119] The test results are shown in Table 1.

[0120] Antibacterial biofilm performance test

[0121] The polyurethane films with coatings obtained in the examples and comparative examples (circular, with a diameter of 2 cm, as the experimental group) and the single polyurethane film (the original polyurethane film group) were immersed in 5 mL of a liquid medium with a Staphylococcus aureus concentration of 1×10 8 CFU / mL, and statically cultured in an incubator at 37 °C for 24 h or 7 days. After taking out the polyurethane film, it was immersed in 2 mL of a thiazolyl blue solution with a concentration of 0.5 mg / mL (using phosphate buffer as the solvent, pH = 7.4), incubated in an incubator at 37 °C for 2 h. After taking out, the polyurethane film was washed with clear water, and then immersed in 2 mL of dimethyl sulfoxide for 2 h. Subsequently, 0.1 mL of the dimethyl sulfoxide solution was added into a 96-well plate, and the absorbance of the solution at 590 nm was measured with an enzyme-linked immunosorbent assay instrument.

[0122] The calculation formula for the activity of the bacterial biofilm is as follows:

[0123] Bacterial biofilm activity = (absorbance of the experimental group / absorbance of the original polyurethane film group) × 100%.

[0124] The test results are shown in Table 1:

[0125] Table 1

[0126]

[0127] From the data in Table 1, it can be seen that the antibacterial coatings formed using quercetin or baicalein have good antibacterial and antibacterial biofilm effects. The polyurethane film without modification with flavonoids has almost no antibacterial effect. In addition, the coated polyurethane films prepared using other flavonoids have poor antibacterial effects.

[0128] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but rather will be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An antibacterial composition, characterized in that Includes flavonoids and polyglutamic acid; The flavonoids include baicalin and / or quercetin.

2. The antibacterial composition according to claim 1, characterized in that The ratio of the flavonoid compound to polyglutamic acid is 1g:(0.1-1)g.

3. The antibacterial composition according to claim 1 or 2, characterized in that: The molecular weight of the polyglutamic acid is 200-500 kDa.

4. An antibacterial coating, characterized in that: The invention is formed from the antibacterial composition according to any one of claims 1 to 3.

5. A method for forming an antibacterial coating as claimed in claim 4, characterized in that: The following steps are involved: S1: soaking a substrate material with active reaction groups on its surface in a flavonoid compound solution, and obtaining a substrate material with flavonoid compounds modified on its surface after reaction; The active reaction groups are hydroxyl groups and / or peroxyhydroxyl groups; S2: Soaking the substrate material whose surface is modified with flavonoid compounds in a polyglutamic acid alkaline solution, and after reaction, obtaining an antibacterial coating formed on the substrate material.

6. The forming method according to claim 5, characterized in that: The substrate material with active reaction groups on the surface is obtained by subjecting the substrate material to plasma treatment; The plasma treatment is carried out in an atmosphere of oxygen, for a time of 3 to 10 minutes, at a power of 50 to 150 W; The base material includes any one or more of polyolefin medical materials, polyurethane medical materials or silicone medical materials; The shape of the base material includes a sheet shape and a tube shape.

7. The forming method according to claim 5 or 6, characterized in that: The solvent of the flavonoid compound solution is water, and the mass concentration of the flavonoid compound solution is 2 to 10 mg / mL; The ratio of the substrate material with active reaction groups on the surface to the flavonoid compound solution is 1g: (100-200)mL.

8. The forming method according to any one of claims 5 to 7, characterized in that: The ratio of the substrate material with the surface modified with flavonoid compounds to the polyglutamic acid alkaline solution is 1 g: (100-200) mL; The mass concentration of the polyglutamic acid alkaline solution is 0.1-5 mg / mL, and the pH is 8-9; The reaction temperature in step S1 is 15-30°C and the reaction time is 0.5-12h; The reaction temperature in step S2 is 15-30°C and the reaction time is 12-36h; The reactions in steps S1 and S2 are both carried out under shaking conditions, and the shaking speed is 200-300 r / min.

9. A medical material, characterized in that: It comprises a medical material substrate and an antibacterial coating formed on the surface of the medical material substrate; The antibacterial coating is the antibacterial coating according to claim 4 or the antibacterial coating formed by the formation method according to any one of claims 5 to 8.

10. The medical material according to claim 9, characterized in that: The thickness of the antibacterial coating is 50 to 200 μm; The medical material matrix is ​​selected from any one or more of polyolefin medical materials, polyurethane medical materials or silicone medical materials; The medical material is a medical device.

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