An antibacterial supramolecular material constructed by oxazine functional groups, and a preparation method and application thereof

Abstract

The application discloses a kind of supermolecular antibacterial material of construction by oxazine functional group composition, preparation method and application, belong to polymer material field.The antibacterial material is composed of supermolecular antibacterial agent, polymer resin material, compatible agent, antioxidant, lubricant, is formed by high temperature mixing, obtains various purposes antibacterial material and product, this antibacterial material has excellent bacteriostatic effect to escherichia coli and staphylococcus aureus, so that material has long-term antibacterial property, simultaneously still has higher strength, is applicable to biliary tract stent etc. human implant medical material, with wide application prospect.

Description

Technical Field

[0001] This invention relates to a supramolecular antibacterial material, and more particularly to a supramolecular antibacterial material constructed from oxazine functional groups, its preparation method, and its applications. It belongs to the field of polymer materials. Background Technology

[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, and non-toxic, with good extensibility, flexibility, transparency, easy processing, electrical insulation, and air permeability. It also has stable physical and chemical properties and is resistant to alkalis and some organic solvents. Currently, it is widely used in medical materials such as various stents and membranes, food packaging (e.g., tea), pharmaceutical packaging (e.g., powders, tablets), packaging for knitted cotton and synthetic fiber products, packaging for daily chemical products such as detergents and cosmetics, and agricultural films. LLDPE has excellent resistance to environmental stress cracking and electrical insulation, high heat resistance, impact resistance, and puncture resistance, and is used in the production of films, daily necessities, pipes, and wires and cables. HDPE is resistant to most acids and alkalis, has low water absorption, maintains flexibility at low temperatures, and has high electrical insulation, making it suitable for medical materials such as artificial joints, artificial bones, artificial larynxes, and orthopedic repair materials. However, polyethylene resin itself does not have antibacterial effects. When it is used for food, medicine and daily chemical packaging, it is prone to bacterial growth. When used as medical material, it can cause problems such as bacterial adhesion and proliferation, biofilm accumulation and reduced service life.

[0003] Patent CN108892851A discloses an antibacterial polyethylene plastic and its preparation method. Polyethylene, acetone, isothiazolinone, antioxidants, compatibilizers, plasticizers, dispersants, benzalkonium chloride, glass fiber, chitosan, phosphorus oxide, and nano-titanium dioxide are mixed in a specific ratio, extruded, granulated, dried, and then injection molded. Although this invention achieves significant antibacterial effects with very small amounts of additives, the excessive number of added substances poses challenges to biocompatibility and product metabolic decomposition. Patent CN114262506A discloses an antibacterial and biodegradable food packaging material and its preparation method. Polyethylene, polyvinyl alcohol, polybutylene succinate, nanocellulose, and fillers are mixed in a high-speed mixer for 3-8 minutes. Then, a bio-based antibacterial agent, flame retardant, and lubricant are added, and mixing continues for 8-20 minutes to obtain a mixture. This mixture is then added to a twin-screw extruder for extrusion granulation. The antibacterial and biodegradable food packaging material of this invention has good antibacterial and degradation properties and is safe and non-toxic. However, the preparation process is relatively complex and time-consuming, and the application range is limited due to the synergistic effect of multiple plastics. Therefore, novel, green, environmentally friendly, highly efficient, long-lasting antibacterial, and simple-to-process antibacterial polymer materials should be further researched and developed. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention discloses a novel and simple antibacterial polymer material and its preparation method. This invention is achieved through the following technical solutions:

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

[0006] 100 parts of polyethylene resin

[0007] 0.5-10 parts of supramolecular antibacterial agent

[0008] Antioxidant 0.1-2 parts

[0009] 0.5-3 parts compatibilizer

[0010] Lubricant 0.1-2 parts;

[0011] in:

[0012] The antioxidant is a combination of hindered phenolic antioxidants and phosphite antioxidants in a 1:1 ratio.

[0013] The compatibilizer is at least one of polypropylene grafted with carboxylic acid, chlorinated polypropylene, or polypropylene grafted with maleic anhydride.

[0014] The lubricant is at least one of N,N-ethylene bis-stearamide, liquid paraffin, and polyhexamethylene monostearate.

[0015] The mass fraction array of the supramolecular antibacterial agent is as follows:

[0016] 1 part of phenolic compounds

[0017] 1 part of amine compound

[0018] 2 parts of paraformaldehyde

[0019] The phenolic compounds are selected from one or more of vanillin, vanillic acid, ethyl vanillin, vanillin, and oleandrin; the amine compounds are selected from one or more of octadecylamine, hexadecylamine, furfurylamine, and dodecyl primary amine.

[0020] The hindered phenolic antioxidants are one or more of antioxidant 1010, antioxidant 1076, antioxidant GA-80, and antioxidant 702, and the phosphite antioxidants are one or more of antioxidant 168, antioxidant P-EPQ, antioxidant 1222, and antioxidant 1425.

[0021] The supramolecular antibacterial material constructed from oxazine functional groups is preferably prepared with an antibacterial agent content of 2.5-7.5 parts.

[0022] This invention also provides a method for preparing a supramolecular antibacterial material constructed from oxazine functional groups, characterized in that the method includes the following steps:

[0023] 1) Synthesis of supramolecular antibacterial agents constructed from oxazine functional groups:

[0024] Paraformaldehyde and amine compounds were mixed evenly in a flask according to the specified ratio. 100 mL of toluene / ethanol solvent was added, and the mixture was heated in an oil bath at 80-90 °C until the solid gradually dissolved. Then, phenolic compounds were added. The reactants were reacted at 80-90 °C with stirring for 12 h. After the reaction was completed, the solution was cooled and crystallized for 12 h to obtain a large amount of crystalline product. The product was washed repeatedly with anhydrous ethanol until the washing liquid was clear and transparent. It was then ground evenly in a mortar and pestle, sieved through a 1000-mesh sieve, and vacuum dried to obtain the supramolecular antibacterial agent.

[0025] 2.) Preparation of supramolecular antibacterial polymer materials constructed from oxazine functional groups:

[0026] The polyethylene resin, supramolecular antibacterial agent, antioxidant, compatibilizer, and lubricant are mixed evenly in a specified ratio. The mixture is then subjected to high-temperature mixing in a twin-screw extruder under the following conditions: main screw speed 160-200 rpm, feed screw speed 18-22 rpm, extrusion temperature 170-210 °C, and extruder current 13-16 A. This yields a supramolecular antibacterial polymer material constructed from oxazine functional groups. The material is then pulverized, granulated, and injection molded to obtain various desired products. The injection pressure is 550 bar, the injection temperature is 180 °C, and the injection time is 30 s; the holding pressure is 500 bar, the holding temperature is 50 °C, and the holding time is 30 s.

[0027] The present invention also provides the application of supramolecular antibacterial materials constructed from oxazine functional groups, characterized in that the supramolecular antibacterial materials constructed from oxazine functional groups are used in implantable medical materials in the human body.

[0028] This invention discloses a supramolecular antibacterial material constructed from oxazine functional groups, which has the following beneficial effects: Compared with traditional polymer resins such as polyethylene resin, the antibacterial material with added supramolecular antibacterial agent is more suitable for use as a human implantable medical material, such as a biliary stent. When the amount of antibacterial agent added is 2.5-7.5 parts, the supramolecular antibacterial material exhibits excellent antibacterial effects against *Escherichia coli* and *Staphylococcus aureus*, suggesting that it has a broad-spectrum antibacterial effect against Gram-negative and Gram-positive bacteria. Furthermore, almost no *E. coli* adheres to the surface of the supramolecular antibacterial material; only a very small number of adhered *E. coli* exhibit surface deformation, shrinkage, and wrinkling, with obvious damage to the cell membrane surface, confirming that the supramolecular antibacterial material can damage bacterial cell walls. Compared with traditional polyethylene resin, this supramolecular antibacterial material is more suitable for use as a human implantable medical material, such as a biliary stent, achieving highly efficient antibacterial activity, preventing bacterial growth and adhesion, and biofilm formation, ensuring long-term effectiveness of the medical material, prolonged patency of the bile duct, and inhibiting further proliferation of malignant tumors.

[0029] In in vitro antitumor cell experiments, the extract of the novel antimicrobial polymer material constructed with oxazine functional groups showed a significant inhibitory effect on human cholangiocarcinoma cells HuCCT1. Overall, the in vitro antitumor cell activity of this novel antimicrobial material increased with increasing extract concentration and the amount of supramolecular antimicrobial agent added. This is of great significance for the application of antimicrobial polymer materials as human biliary scaffolds and the treatment of malignant biliary obstruction. Attached Figure Description

[0030] Figure 1 The in vitro antibacterial results of a supramolecular antibacterial material constructed from oxazine functional groups.

[0031] Figure 2 SEM image of a supramolecular antibacterial material constructed from oxazine functional groups against Escherichia coli adhesion.

[0032] Figure 3 The results show that a supramolecular antibacterial material constructed from oxazine functional groups inhibits the activity of human biliary tract cancer cells. Detailed Implementation

[0033] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. The described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0034] Please see Figure 1-3This invention provides a supramolecular antibacterial material constructed from oxazine functional groups and its preparation method. The supramolecular antibacterial agent constructed from oxazine functional groups is mixed with polyethylene resin in different proportions and 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 it has in vitro activity against human cholangiocarcinoma cells HuCCT1.

[0035] Example 1

[0036] 0.14 mol paraformaldehyde and 0.066 mol furfurylamine were mixed in a 200 mL flask, and 100 mL of toluene / ethanol solvent was added. The mixture was heated in an oil bath at 80–90 °C at 250 rpm. After the solid gradually dissolved, 0.066 mol ethyl vanillin was added. The reaction mixture was then allowed to react for 12 hours at 80–90 °C and 250 rpm. After the reaction was completed, the mixture was cooled and crystallized, yielding a large amount of white crystalline product at the bottom of the beaker. The product was washed repeatedly with anhydrous ethanol and dried to obtain a supramolecular antibacterial agent constructed from oxazine functional groups.

[0037] Using 100 parts of polyethylene resin as the matrix, 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 were added. The mixture was then high-temperature compounded in a twin-screw extruder at a main screw speed of 160-200 rpm, a feed screw speed of 18-22 rpm, an extrusion temperature range of 170-210 °C, and an extruder current of 13-16 A to obtain a supramolecular antibacterial polymer material constructed from oxazine functional groups. This material was then pulverized and granulated. The desired product was obtained by using an injection pressure of 550 bar, an injection temperature of 180 °C, and an injection time of 30 s; and a holding pressure of 500 bar, a holding temperature of 50 °C, and a holding time of 30 s.

[0038] The antibacterial properties of the materials were investigated using a co-culture + plate coating method. The above samples were subjected to antibacterial experiments, and the obtained antibacterial material showed a 99.98% inhibitory effect against *Escherichia coli*, and also exhibited anti-*E. coli* adhesion activity. The obtained antibacterial material also showed a 99.98% inhibitory effect against *Staphylococcus aureus*.

[0039] Based on the application of this supramolecular antibacterial material constructed from oxazine functional groups, we conducted in vitro anti-malignant tumor experiments using human cholangiocarcinoma cells (HuCCT1). The supramolecular antibacterial material PE / Bz was prepared into a biliary scaffold and co-cultured with human cholangiocarcinoma cells (HuCCT1) in vitro. The culture medium was diluted to 100%, 75%, 50%, and 25%, respectively. The results are attached. Figure 3As shown, when the dilution concentration is 100%, the supramolecular antibacterial material PE / Bz can inhibit the relative activity of human cholangiocarcinoma cells HuCCT1 by as little as 18.15%. This demonstrates that, compared to traditional polyethylene resin, this supramolecular antibacterial material is more suitable for use as implantable medical materials such as biliary stents. It can achieve highly efficient antibacterial activity, preventing bacterial growth, adhesion, and biofilm formation, ensuring the long-term effectiveness of the medical material, maintaining bile duct patency for an extended period, and inhibiting further proliferation of malignant tumors.

[0040] Example 2

[0041] A supramolecular antibacterial material PE / Bz constructed from oxazine functional groups was prepared using a method essentially the same as in Example 1, except that vanillin was used instead of ethyl vanillin and octadecylamine was used instead of furfurylamine. The remaining parameters were the same as in Example 1.

[0042] The antibacterial properties of the materials were investigated using a co-culture + plate coating method. The above samples were subjected to antibacterial experiments, and the obtained antibacterial material showed an inhibitory effect of 97.50% against *Escherichia coli*, and also exhibited anti-*E. coli* adhesion activity. The obtained antibacterial material also showed an inhibitory effect of 89.0% against *Staphylococcus aureus*.

[0043] Example 3

[0044] A supramolecular antibacterial material PE / Bz constructed from oxazine functional groups was prepared using a method essentially the same as in Example 1, except that vanillin was used instead of ethyl vanillin and hexadecylamine was used instead of furfurylamine. The remaining parameters were the same as in Example 1.

[0045] The antibacterial properties of the materials were investigated using a co-culture + plate coating method. The above samples were subjected to antibacterial experiments, and the obtained antibacterial material showed an inhibitory effect of 63.50% against *Escherichia coli*, but did not exhibit any anti-*E. coli* adhesion activity. The obtained antibacterial material also showed an inhibitory effect of 57.0% against *Staphylococcus aureus*.

[0046] Example 4

[0047] A supramolecular antibacterial material PE / Bz constructed from oxazine functional groups was prepared using a method essentially the same as in Example 1, except that the main screw speed in the twin-screw extruder was increased to 170~210 rpm, while the feed screw speed remained unchanged at 18~22 rpm and the extrusion temperature range remained unchanged at 170~210 °C.

[0048] The antibacterial properties of the materials were investigated using a co-culture + plate coating method. The above samples were subjected to antibacterial experiments, and the obtained antibacterial material showed an inhibitory effect of 84.50% against *Escherichia coli*, and also exhibited anti-*E. coli* adhesion activity. The obtained antibacterial material also showed an inhibitory effect of 80.0% against *Staphylococcus aureus*.

[0049] Example 5

[0050] A supramolecular antibacterial material PE / Bz constructed from oxazine functional groups was prepared using a method essentially the same as in Example 1, except that the extrusion temperature range in the twin-screw extruder was changed to 150~190 °C, while the main screw speed of 160~200 rpm and the feed screw speed of 18~22 rpm remained unchanged.

[0051] The antibacterial properties of the materials were investigated using a co-culture + plate coating method. The above samples were subjected to antibacterial experiments, and the obtained antibacterial material showed an inhibitory effect of 78.40% against *Escherichia coli*, and also exhibited anti-*E. coli* adhesion activity. The obtained antibacterial material also showed an inhibitory effect of 72.5% against *Staphylococcus aureus*.

[0052] Compare with Example 6

[0053] As a blank control, PE material was prepared using a method essentially the same as in Example 1, except that 100 parts of polyethylene resin were used as the matrix, and only 0.1-2 parts of antioxidant, 0.5-3 parts of compatibilizer, and 0.1-2 parts of lubricant were added; no supramolecular antibacterial agent was added. The antibacterial properties of the material were examined using a co-culture + plate coating method. The above samples were subjected to antibacterial experiments. The control sample PE without supramolecular antibacterial agent showed no inhibitory effect on Escherichia coli and Staphylococcus aureus, indicating that polyethylene resin itself has no antibacterial effect.

[0054] Table 1. Anti-Escherichia coli test results of PE / Bz prepared in Examples 1-6 (R 1-3 (Different groups of antibacterial agents)

[0055] Group <![CDATA[R1]]> <![CDATA[R2]]> <![CDATA[R3]]> engine speed / rpm Temperature / °C Antibacterial rate (%) Example 1 <![CDATA[-OCH2CH3]]> -CHO <![CDATA[-C5H5O]]> 160~200 170~210 99.98 Example 2 <![CDATA[-OCH3]]> -CHO <![CDATA[-C 18 H 37 ]]> 160~200 170~210 97.50 Example 3 <![CDATA[-OCH3]]> <![CDATA[-CH2OH]]> <![CDATA[-C 16 H 33 ]]> 160~200 170~210 63.50 Example 4 <![CDATA[-OCH2CH3]]> -CHO <![CDATA[-C5H5O]]> 170~210 170~210 84.50 Example 5 <![CDATA[-OCH2CH3]]> -CHO <![CDATA[-C5H5O]]> 160~200 150~190 78.40 Example 6 - - - 160~200 170~210 0

[0056] Table 2. Results of Staphylococcus aureus resistance tests (R) of PE / Bz prepared in Examples 1-6 1-3 (Different groups of antibacterial agents)

[0057] Group <![CDATA[R1]]> <![CDATA[R2]]> <![CDATA[R3]]> engine speed / rpm Temperature / °C Antibacterial rate (%) Example 1 <![CDATA[-OCH2CH3]]> -CHO <![CDATA[-C5H5O]]> 160~200 170~210 99.98 Example 2 <![CDATA[-OCH3]]> -CHO <![CDATA[-C 18 H 37 ]]> 160~200 170~210 89.0 Example 3 <![CDATA[-OCH3]]> <![CDATA[-CH2OH]]> <![CDATA[-C 16 H 33 ]]> 160~200 170~210 57.0 Example 4 <![CDATA[-OCH2CH3]]> -CHO <![CDATA[-C5H5O]]> 170~210 170~210 80.0 Example 5 <![CDATA[-OCH2CH3]]> -CHO <![CDATA[-C5H5O]]> 160~200 150~190 72.50 Example 6 - - - 160~200 170~210 0

[0058] See also Figure 1 Referring to Example 1, compared with polyethylene resin, the supramolecular antibacterial material PE / Bz constructed from oxazine functional groups of the present invention has an antibacterial effect of up to 99.98% against Escherichia coli and Staphylococcus aureus when the amount of antibacterial agent added is 2.5 parts. It is speculated that PE / Bz has a broad-spectrum antibacterial effect against Gram-negative and Gram-positive bacteria.

[0059] See Figure 2Referring to Example 1, almost no E. coli adhered to the surface of the antibacterial polymer material PE / Bz. Only a very small number of E. coli adhered to the surface and showed deformation, shrinkage, and wrinkling. The cell membrane surface was clearly damaged, which also confirmed that the antibacterial polymer material PE / Bz can damage the bacterial cell wall.

[0060] In in vitro antitumor cell experiments of the antibacterial polymer material PE / Bz, the material extract showed a significant inhibitory effect on human cholangiocarcinoma cells HuCCT1.

[0061] See Figure 3 Referring to Example 1, the overall trend shows that the in vitro antitumor cell activity of the antibacterial polymer material PE / Bz increases with increasing extract concentration and with increasing supramolecular antibacterial agent dosage. When the culture medium dilution concentration is 100%, the relative activity of the supramolecular antibacterial material PE / Bz against human cholangiocarcinoma cells HuCCT1 can be inhibited by as little as 18.15%. Compared with polyethylene resin, the antibacterial polymer material PE / Bz is more suitable as a medical material such as biliary stents, achieving highly efficient antibacterial activity, preventing bacterial growth and adhesion, and forming biofilms, thereby reducing the use of antibiotics and ensuring the long-term patency of medical stents.

[0062] The melt viscosity, mechanical properties, and crystallinity of the antibacterial polymer material PE / Bz change. With increasing amounts of supramolecular antibacterial agent, the melt viscosity of PE / Bz increases, while its crystallinity and melting properties remain largely unchanged. Therefore, the actual processing time, pressure, and temperature can be adjusted according to the length, thickness, and strength requirements of different products. Furthermore, with increasing amounts of supramolecular antibacterial agent, the tensile strength and flexural strength of the antibacterial polymer material PE / Bz increase significantly.

[0063] This invention is not limited to the above-described optional embodiments. Anyone can derive other various forms of products under the guidance of this invention. However, regardless of any changes made in their shape or structure, any technical solution that falls within the scope of the claims of this invention shall be protected by this invention.

Claims

1. A supramolecular antibacterial material constructed from oxazine functional groups, characterized in that, The supramolecular antibacterial material comprises the following components in parts by mass and is prepared by the following steps: 100 parts of polyethylene resin 0.5-10 parts of supramolecular antibacterial agent Antioxidant 0.1-2 parts 0.5-3 parts compatibilizer Lubricant 0.1-2 parts; in: The antioxidant is a combination of hindered phenolic antioxidants and phosphite antioxidants in a 1:1 ratio. The compatibilizer is at least one of polypropylene grafted with carboxylic acid, chlorinated polypropylene, or polypropylene grafted with maleic anhydride. The lubricant is at least one of N,N-ethylene bis-stearamide, liquid paraffin, and polyhexamethylene monostearate. The raw materials for preparing the supramolecular antibacterial agent include phenolic compounds, amine compounds, and paraformaldehyde, with a molar ratio of paraformaldehyde:amine compounds:phenolic compounds = 0.14:0.066:0.

066. The phenolic compounds are selected from one or more of vanillin, vanillic acid, ethyl vanillin, vanillin, and oleandrin; the amine compounds are selected from one or more of octadecylamine, hexadecylamine, furfurylamine, and dodecyl primary amine. The supramolecular antibacterial material is prepared by the following steps: 1) Synthesis of supramolecular antibacterial agents constructed from oxazine functional groups: Paraformaldehyde and amine compounds were mixed evenly in a flask according to the specified ratio. 100 mL of toluene / ethanol solvent was added, and the mixture was heated in an oil bath at 80-90 °C until the solid gradually dissolved. Then, phenolic compounds were added. The reactants were reacted at 80-90 °C with stirring for 12 h. After the reaction was completed, the solution was cooled and crystallized for 12 h to obtain a large amount of crystalline product. The product was washed repeatedly with anhydrous ethanol until the washing liquid was clear and transparent. It was then ground evenly in a mortar and pestle, sieved through a 1000-mesh sieve, and vacuum dried to obtain the supramolecular antibacterial agent. 2.) Preparation of supramolecular antibacterial polymer materials constructed from oxazine functional groups: The polyethylene resin, supramolecular antibacterial agent, antioxidant, compatibilizer, and lubricant are mixed evenly in a specified ratio. The mixture is then subjected to high-temperature mixing in a twin-screw extruder under the following conditions: main screw speed 160-200 rpm, feed screw speed 18-22 rpm, extrusion temperature 170-210℃, and extruder current 13-16 A. This yields a supramolecular antibacterial polymer material constructed from oxazine functional groups. The material is then pulverized, granulated, and injection molded to obtain various desired products. The injection pressure is 550 bar, the injection temperature is 180℃, and the injection time is 30 s; the holding pressure is 500 bar, the holding temperature is 50℃, and the holding time is 30 s.

2. The supramolecular antibacterial material as described in claim 1, characterized in that, The hindered phenolic antioxidant is one or more of antioxidant 1010, antioxidant 1076, antioxidant GA-80, and antioxidant 702, and the phosphite antioxidant is one or more of antioxidant 168 and antioxidant P-EPQ.

3. The supramolecular antibacterial material as described in claim 1, characterized in that, The supramolecular antibacterial material comprises the following components in parts by mass: 100 parts of polyethylene resin 2.5-7.5 parts of supramolecular antibacterial agent Antioxidant 0.1-2 parts 0.5-3 parts compatibilizer Lubricant 0.1-2 parts.

4. The application of a supramolecular antibacterial material constructed from oxazine functional groups as described in claim 1, 2, or 3, characterized in that, Application of supramolecular antibacterial materials constructed with oxazine functional groups in the preparation of implantable medical materials.

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