Supramolecular antibacterial material constructed by oxazine functional groups as well as preparation method and application of supramolecular antibacterial material

Abstract

The invention discloses composition, a preparation method and application of a supramolecular antibacterial material constructed by oxazine functional groups, and belongs to the field of high polymer materials. The antibacterial material is composed of a supramolecular antibacterial agent, a macromolecular resin material, a compatilizer, an antioxidant and a lubricant, antibacterial materials and products for various purposes are obtained through high-temperature mixing molding, and the antibacterial material has an excellent antibacterial effect on escherichia coli and staphylococcus aureus, so that the material has long-term antibacterial property, and the service life of the antibacterial material is prolonged. And meanwhile, the material also has relatively high strength, is suitable for human body implantation medical materials such as biliary tract stents and the like, and has a wide application prospect.

Description

Technical Field

[0001] The present invention relates to a supramolecular antibacterial material, in particular to a supramolecular antibacterial material constructed by oxazine functional groups and a preparation method and application thereof, belonging to the field of polymer materials. Background Art

[0002] Polyethylene resin is one of the most widely used polymer resin materials, including low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE) and high-density polyethylene (HDPE). LDPE is tasteless, odorless, non-toxic, and has good extensibility, softness, transparency, easy processing, electrical insulation and air permeability. At the same time, its physical and chemical properties are stable, and it is resistant to alkali and some organic solvents. At present, it has been widely used as medical materials such as various stents and membranes, food packaging such as tea, drug packaging such as powders and tablets, fiber product packaging such as knitted cotton products and chemical fiber products, daily chemical packaging such as detergents and cosmetics, agricultural films, etc. LLDPE has excellent environmental stress cracking resistance and electrical insulation, high heat resistance, impact resistance and puncture resistance, etc., and is used in the production of films, daily necessities, pipes, wires and cables, etc. HDPE can withstand the erosion of most acids and alkalis, has low water absorption, can still maintain softness at low temperatures, has high electrical insulation, and is suitable for medical materials such as artificial joints, artificial bones, artificial larynx, orthopedic repair materials, etc. However, polyethylene resin itself has no antibacterial effect. When it is used as food, medicine and daily chemical packaging, it is easy to cause bacterial growth. When used as a medical material, problems such as bacterial adhesion and growth, biofilm accumulation, and reduced service life will occur.

[0003] Patent CN108892851A discloses a polyethylene antibacterial plastic and a preparation method thereof, wherein polyethylene, acetone, isothiazolinone, antioxidant, compatibilizer, plasticizer, dispersant, benzalkonium chloride, glass fiber, chitosan, phosphorus oxide and nano titanium dioxide are mixed in proportion, extruded, granulated, dried and then injection molded. Although the present invention can obviously play an antibacterial role with a small amount, the added substances are too numerous, and its biocompatibility and product metabolic decomposition become problems. Patent CN114262506A discloses an antibacterial and degradable food packaging material and a preparation method thereof, wherein polyethylene, polyvinyl alcohol, polybutylene succinate, nanocellulose and filler are mixed in a high mixer for 3-8 minutes, then a bio-based antibacterial agent, a flame retardant and a lubricant are added and mixed for 8-20 minutes to obtain a mixed material, and the mixed material is added to a twin-screw extruder for extrusion granulation. The antibacterial and degradable food packaging material of the invention has good antibacterial and degradable properties and is safe and non-toxic, but the preparation process is relatively complicated and time-consuming, and the synergistic effect of multiple plastics has a limited application range. Therefore, new, green, environmentally friendly, efficient, long-lasting antibacterial and simple process antibacterial polymer materials should be further studied and developed. Summary of the invention

[0004] In view of the shortcomings of the prior art, the present invention discloses a novel antibacterial polymer material with simple process and a preparation method thereof. The present invention is achieved through the following technical solutions:

[0005] A supramolecular antibacterial material constructed by oxazine functional groups, characterized in that the supramolecular antibacterial material comprises the following components in parts by mass:

[0006]

[0007] in:

[0008] The antioxidant is a combination of hindered phenol antioxidant and phosphite antioxidant, the ratio of the two is 1:1.

[0009] The compatibilizer is at least one of polypropylene grafted carboxylic acid, chlorinated polypropylene, and polypropylene grafted maleic anhydride.

[0010] The lubricant is at least one of N,N-ethylenebisstearamide, liquid paraffin, and hexaglycerol monostearate.

[0011] The mass fraction of the supramolecular antibacterial agent is as follows:

[0012] 1 part of phenolic compounds

[0013] 1 part of amine compound

[0014] 2 parts of paraformaldehyde

[0015] The phenolic compound is one or more selected from vanillic alcohol, vanillic acid, ethyl vanillin, vanillin, and apocynin; the amine compound is one or more selected from octadecylamine, hexadecylamine, furfurylamine, and dodecyl primary amine.

[0016] The hindered phenol antioxidants are one or more of antioxidant 1010, antioxidant 1076, antioxidant GA-80, and antioxidant 702; the phosphite antioxidants are one or more of antioxidant 168, antioxidant P-EPQ, antioxidant 1222, and antioxidant 1425.

[0017] The amount of antibacterial agent added to the supramolecular antibacterial material constructed by oxazine functional groups is preferably 2.5-7.5 parts.

[0018] The present invention also provides a method for preparing a supramolecular antibacterial material constructed by oxazine functional groups, characterized in that the method comprises the following steps:

[0019] 1) Synthesis of supramolecular antibacterial agents constructed by oxazine functional groups:

[0020] Take polyformaldehyde and amine compounds in a flask in proportion and mix them evenly, add 100 ml of solvent toluene / ethanol, heat in an oil bath at 80-90° C. until the solid gradually dissolves, then add the phenolic compound, react at 80-90° C. and stir for 12 hours, after the reaction is completed, cool the solution and crystallize for 12 hours to obtain a large amount of crystalline product, wash the product with anhydrous ethanol several times until the washing liquid is clear and transparent, grind it evenly with a mortar, sieve it with a 1000-mesh sieve, and dry it in a vacuum to obtain the supramolecular antibacterial agent;

[0021] 2.) Preparation of supramolecular antibacterial polymer materials constructed by oxazine functional groups:

[0022] The polyethylene resin, supramolecular antibacterial agent, antioxidant, compatibilizer and lubricant are uniformly mixed in proportion, and mixed at high temperature in a twin-screw extruder under the conditions of main engine screw speed of 160-200rpm, feeding screw speed of 18-22rpm, extrusion temperature of 170-210°C and extruder current of 13-16A to obtain a supramolecular antibacterial polymer material constructed by oxazine functional groups, and then crushed and granulated, and various required products are obtained by injection molding, wherein the injection pressure is 550 bar, the injection temperature is 180°C, and the injection time is 30s; the holding pressure is 500 bar, the holding temperature is 50°C, and the holding time is 30s.

[0023] The present invention also provides the application of the supramolecular antibacterial material constructed by the oxazine functional group, characterized in that the supramolecular antibacterial material constructed by the oxazine functional group is used in medical materials implanted in the human body.

[0024] The supramolecular antibacterial material constructed by oxazine functional groups of the present invention has the following beneficial effects: The structure of the supramolecular antibacterial agent constructed by oxazine groups is shown in the attached Figure 1 . Compared with traditional polymer resins such as polyethylene resins, antibacterial materials with added supramolecular antibacterial agents are more suitable for use as medical materials implanted in the human body, such as biliary stents. When the amount of the antibacterial agent added in the present invention is 2.5-7.5 parts, the supramolecular antibacterial material has excellent antibacterial effects on Escherichia coli and Staphylococcus aureus, and it is speculated that the supramolecular antibacterial material has a broad-spectrum antibacterial effect on Gram-negative and Gram-positive bacteria. In addition, it was observed that almost no Escherichia coli adhered to the surface of the supramolecular antibacterial material, and only a very small number of adhered Escherichia coli were observed to be deformed, atrophied, and wrinkled on the surface, and the cell membrane surface was clearly destroyed, which also confirmed that the supramolecular antibacterial material can damage the bacterial cell wall. Compared with traditional polyethylene resins, this supramolecular antibacterial material is more suitable for use as medical materials implanted in the human body, such as biliary stents, and can achieve efficient antibacterial, avoid bacterial growth and adhesion, form biofilms, etc., ensure the long-term effectiveness of medical materials, long-term patency of the bile duct, and inhibit further proliferation of malignant tumors.

[0025] In the in vitro anti-tumor cell experiment of the supramolecular antibacterial polymer material constructed by oxazine functional groups, the extract of the new antibacterial material had a significant inhibitory effect on human cholangiocarcinoma cell HuCCT1. In general, the in vitro anti-tumor cell ability of the new antibacterial material increased with the increase of the extract concentration and the increase of the amount of supramolecular antibacterial agent added, which is of great significance for the use of antibacterial polymer materials as human biliary stents and the treatment of malignant biliary obstruction. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic diagram of the structure of supramolecular antibacterial agent constructed by oxazine groups

[0027] Figure 2 In vitro antibacterial results of a supramolecular antibacterial material constructed by oxazine functional groups

[0028] Figure 3 SEM image of a supramolecular antibacterial material constructed with oxazine functional groups to resist Escherichia coli adhesion

[0029] Figure 4 The results show that a supramolecular antibacterial material constructed with oxazine functional groups inhibits the activity of human biliary cancer cells. DETAILED DESCRIPTION

[0030] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. The described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] See also Figure 1-4 The present invention provides a supramolecular antibacterial material constructed by oxazine functional groups and a preparation method thereof. The supramolecular antibacterial agent constructed by oxazine functional groups is used, and the antibacterial agent is mixed with polyethylene resin in different proportions at high temperature to obtain an in-situ modified material. The material itself has antibacterial properties, the surface of the material is resistant to the adhesion of Escherichia coli, and has in vitro activity against human bile duct cancer cell HuCCT1.

[0032] Example 1

[0033] Take 0.14 mol of paraformaldehyde and 0.066 mol of furfurylamine and place them in a 200 ml flask, mix them, add 100 ml of solvent toluene / ethanol, heat and react in an oil bath at 80-90 ° C, with a speed of 250 rpm; after the solid gradually dissolves, add 0.066 mol of ethyl vanillin. Then the reactants react at 80-90 ° C and 250 rpm for 12 hours. After the reaction is completed, cool and crystallize, and a large amount of white crystalline product is obtained at the bottom of the beaker. Wash with anhydrous ethanol several times and dry to obtain a supramolecular antibacterial agent constructed by oxazine functional groups.

[0034] Take 100 parts of polyethylene resin as the matrix, add 0.5-10 parts of supramolecular antibacterial agent, 0.1-2 parts of antioxidant, 0.5-3 parts of compatibilizer and 0.1-2 parts of lubricant respectively. In a twin-screw extruder, the main screw speed is 160-200rpm, the feeding screw speed is 18-22rpm, the extrusion temperature range is 170-210℃ and the extruder current is 13-16A, and the supramolecular antibacterial polymer material constructed by oxazine functional groups is obtained by high-temperature mixing and crushing and granulation. The injection pressure is 550bar, the injection temperature is 180℃, and the injection time is 30s; the holding pressure is 500bar, the holding temperature is 50℃, and the holding time is 30s, and the desired product can be obtained.

[0035] The antibacterial properties of the material were investigated by co-culture + plate coating method. The antibacterial test of the above samples showed that the antibacterial effect of the obtained antibacterial material on Escherichia coli reached 99.98%, and it had the effect of resisting the adhesion of Escherichia coli. The antibacterial effect of the obtained antibacterial material on Staphylococcus aureus also reached 99.98%.

[0036] Based on the application of this supramolecular antibacterial material constructed by oxazine functional groups, we conducted an in vitro anti-tumor experiment on the material using human cholangiocarcinoma cell HuCCT1. The supramolecular antibacterial material PE / Bz was prepared into a biliary stent and co-cultured with human cholangiocarcinoma cell HuCCT1 in vitro, and the cultured cell fluid was diluted to 100%, 75%, 50% and 25% respectively. The results are shown in the attached figure. Figure 4 As shown in the figure, when the dilution concentration is 100%, the relative activity of supramolecular antibacterial material PE / Bz on human cholangiocarcinoma cell HuCCT1 can be inhibited to as low as 18.15%. It can be seen that this supramolecular antibacterial material is more suitable for use as a medical material implanted in the human body, such as a biliary stent, compared with traditional polyethylene resins. It can achieve high-efficiency antibacterial, avoid bacterial growth and adhesion, form biofilms, etc., ensure the long-term effectiveness of medical materials, long-term patency of the bile duct, and inhibit further proliferation of malignant tumors.

[0037] Example 2

[0038] A supramolecular antibacterial material PE / Bz constructed by oxazine functional groups was prepared by a method basically the same as in Example 1, except that vanillin was used as a raw material instead of ethyl vanillin, and octadecylamine was used as a raw material instead of furfurylamine. The other parameters were the same as in Example 1.

[0039] The antibacterial properties of the material were investigated by co-culture + plate coating method. The antibacterial test of the above samples showed that the antibacterial effect of the obtained antibacterial material on Escherichia coli reached 97.50%, and it had the effect of resisting the adhesion of Escherichia coli. The antibacterial effect of the obtained antibacterial material on Staphylococcus aureus also reached 89.0%.

[0040] Example 3

[0041] A supramolecular antibacterial material PE / Bz constructed by oxazine functional groups was prepared by a method basically the same as in Example 1, except that vanillin was used as a raw material instead of ethyl vanillin, and hexadecylamine was used as a raw material instead of furfurylamine. The other parameters were the same as in Example 1.

[0042] The antibacterial properties of the material were investigated by co-culture + plate coating method. The antibacterial test of the above samples showed that the antibacterial effect of the obtained antibacterial material on Escherichia coli reached 63.50%, but it did not have the effect of preventing Escherichia coli from adhering. The antibacterial effect of the obtained antibacterial material on Staphylococcus aureus also reached 57.0%.

[0043] Example 4

[0044] A supramolecular antibacterial material PE / Bz constructed with oxazine functional groups was prepared by a method basically the same as in Example 1, except that the main screw speed in the twin-screw extruder was increased to 170-210 rpm, the feed screw speed was 18-22 rpm and the extrusion temperature range was kept unchanged at 170-210°C.

[0045] The antibacterial properties of the material were investigated by co-culture + plate coating method. The antibacterial test of the above samples showed that the antibacterial effect of the obtained antibacterial material on Escherichia coli reached 84.50%, and it had the effect of resisting the adhesion of Escherichia coli. The antibacterial effect of the obtained antibacterial material on Staphylococcus aureus also reached 80.0%.

[0046] Example 5

[0047] A supramolecular antibacterial material PE / Bz constructed with oxazine functional groups was prepared by a method basically the same as in Example 1, except that the extrusion temperature range in the twin-screw extruder was changed to 150-190°C, and the main screw speed of 160-200rpm and the feeding screw speed of 18-22rpm remained unchanged.

[0048] The antibacterial properties of the material were investigated by co-culture + plate coating method. The antibacterial test of the above samples showed that the antibacterial effect of the obtained antibacterial material on Escherichia coli reached 78.40%, and it had the effect of resisting the adhesion of Escherichia coli. The antibacterial effect of the obtained antibacterial material on Staphylococcus aureus also reached 72.5%.

[0049] Comparative Example 6

[0050] As a blank control sample, a PE material was prepared by the same method as in Example 1, except that 100 parts of polyethylene resin was taken as the matrix, only 0.1-2 parts of antioxidant, 0.5-3 parts of compatibilizer, and 0.1-2 parts of lubricant were added, and no supramolecular antibacterial agent was added. The antibacterial properties of the material were investigated by co-culture + plate coating method, and the above samples were subjected to antibacterial experiments. The control sample PE without adding supramolecular antibacterial agent had no antibacterial effect on Escherichia coli and Staphylococcus aureus, that is, the polyethylene resin itself had no antibacterial effect.

[0051] Table 1 Anti-Escherichia coli test results of PE / Bz prepared in Examples 1 to 6 (R 1-3 See Figure 1 )

[0052]

[0053] Table 2 Anti-Staphylococcus aureus test results of PE / Bz prepared in Examples 1 to 6 (R 1-3 See Figure 1 )

[0054]

[0055]

[0056] See also Figure 2 Taking Example 1 as a reference, compared with polyethylene resin, the supramolecular antibacterial material PE / Bz constructed by oxazine functional groups of the present invention has an antibacterial effect of up to 99.98% on Escherichia coli and Staphylococcus aureus when the antibacterial agent addition amount is 2.5 parts. It is speculated that PE / Bz has a broad-spectrum antibacterial effect on Gram-negative bacteria and Gram-positive bacteria.

[0057] See also Figure 3 Taking Example 1 as a reference, it can be observed that there is almost no E. coli adhesion on the surface of the antibacterial polymer material PE / Bz, and only a few E. coli adhesion are observed to be deformed, shrunk, and wrinkled on the surface. It can be clearly seen that the cell membrane surface is destroyed, which also confirms that the antibacterial polymer material PE / Bz can damage the bacterial cell wall.

[0058] In the in vitro anti-tumor cell experiment of the antibacterial polymer material PE / Bz, the material extract had a significant inhibitory effect on human bile duct cancer cell HuCCT1.

[0059] See also Figure 4 , taking Example 1 as a reference, from the overall trend, the in vitro anti-tumor cell ability of the antibacterial polymer material PE / Bz increases with the increase of the extract concentration and the increase of the amount of supramolecular antibacterial agent added. When the concentration of the culture diluent is 100%, the supramolecular antibacterial material PE / Bz can inhibit the relative activity of human bile duct cancer cell HuCCT1 to as low as 18.15%. Compared with polyethylene resin, the antibacterial polymer material PE / Bz is more suitable as a medical material such as biliary stents, etc., which can achieve efficient antibacterial, avoid bacterial growth and adhesion, form biofilms, etc., thereby reducing the use of antibiotics and ensuring the long-term patency of medical stents.

[0060] The melt viscosity, mechanical properties and crystallization properties of the antibacterial polymer material PE / Bz change. With the increase of the amount of supramolecular antibacterial agent added, the melt viscosity of PE / Bz increases, and the crystallization and melting properties of PE / Bz remain basically unchanged. The actual processing time, processing pressure and processing temperature can be adjusted according to the length, thickness and strength requirements of different products. With the increase of the amount of supramolecular antibacterial agent added, the tensile strength and bending strength of the antibacterial polymer material PE / Bz increase significantly.

[0061] The present invention is not limited to the above-mentioned optional implementation modes. Anyone can derive other various forms of products under the inspiration of the present invention. However, no matter what changes are made in the shape or structure, all technical solutions that fall within the scope defined by the claims of the present invention fall within the protection scope of the present invention.

Claims

1. A supramolecular antibacterial material constructed by oxazine functional groups, characterized in that: The supramolecular antibacterial material comprises the following components by mass: in: The antioxidant is a combination of hindered phenol antioxidant and phosphite antioxidant, the ratio of the two is 1:

1. The compatibilizer is at least one of polypropylene grafted carboxylic acid, chlorinated polypropylene, and polypropylene grafted maleic anhydride. The lubricant is at least one of N,N-ethylenebisstearamide, liquid paraffin, and hexaglycerol monostearate. The mass fraction of the supramolecular antibacterial agent is as follows: 1 part of phenolic compounds 1 part of amine compound 2 parts of paraformaldehyde The phenolic compound is one or more selected from vanillic alcohol, vanillic acid, ethyl vanillin, vanillin, and apocynin; the amine compound is one or more selected from octadecylamine, hexadecylamine, furfurylamine, and dodecyl primary amine.

2. The supramolecular antibacterial material according to claim 1, characterized in that: The hindered phenol antioxidants are one or more of antioxidant 1010, antioxidant 1076, antioxidant GA-80, and antioxidant 702; the phosphite antioxidants are one or more of antioxidant 168, antioxidant P-EPQ, antioxidant 1222, and antioxidant 1425.

3. The supramolecular antibacterial material according to claim 1, characterized in that: The supramolecular antibacterial material comprises the following components by mass:

4. A method for preparing a supramolecular antibacterial material constructed by oxazine functional groups as claimed in claim 1, 2 or 3, characterized in that: The method comprises the following steps: 1) Synthesis of supramolecular antibacterial agents constructed by oxazine functional groups: Take polyformaldehyde and amine compounds in a flask in proportion and mix them evenly, add 100 ml of solvent toluene / ethanol, heat in an oil bath at 80-90° C. until the solid gradually dissolves, then add the phenolic compound, react at 80-90° C. and stir for 12 hours, after the reaction is completed, cool the solution and crystallize for 12 hours to obtain a large amount of crystalline product, wash the product with anhydrous ethanol several times until the washing liquid is clear and transparent, grind it evenly with a mortar, sieve it with a 1000-mesh sieve, and dry it in a vacuum to obtain the supramolecular antibacterial agent; 2) Preparation of supramolecular antibacterial polymer materials constructed by oxazine functional groups: The polyethylene resin, supramolecular antibacterial agent, antioxidant, compatibilizer and lubricant are uniformly mixed in proportion, and mixed at high temperature in a twin-screw extruder under the conditions of main engine screw speed of 160-200rpm, feeding screw speed of 18-22rpm, extrusion temperature of 170-210°C and extruder current of 13-16A to obtain a supramolecular antibacterial polymer material constructed by oxazine functional groups, and then crushed and granulated, and various required products are obtained by injection molding, wherein the injection pressure is 550 bar, the injection temperature is 180°C, and the injection time is 30s; the holding pressure is 500 bar, the holding temperature is 50°C, and the holding time is 30s.

5. An application of the supramolecular antibacterial material constructed by oxazine functional groups as claimed in claim 1, 2 or 3, characterized in that: Application of supramolecular antibacterial materials constructed by oxazine functional groups in medical materials implanted in the human body.

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