An antibacterial and high-temperature resistant medical film and its preparation method

Abstract

The present invention discloses an antibacterial and high-temperature resistant medical film and a preparation method thereof, belonging to the technical field of medical film materials. It is prepared from polyvinyl alcohol, deionized water, glutaraldehyde aqueous solution, multi-effect antibacterial agent, N,N-dimethylformamide, pre-gelatinized corn starch and pretreated xanthan gum in a dosage ratio of 40-60 g: 200-300 mL: 10-20 mL: 5-15 g: 100-200 mL: 12-18 g: 6-12 g. The addition of pre-gelatinized corn starch and xanthan gum endows the medical film with good water resistance, high-temperature resistance, degradability and mechanical properties; the prepared multi-effect antibacterial agent greatly enhances the antibacterial performance of the medical film and has a certain degree of high-temperature resistance, and the performance is long-term stable; therefore, the medical film prepared by the present invention has good water resistance, high mechanical strength, stable and efficient antibacterial performance and high-temperature resistance, is degradable, and has important application value in the technical field of medical film materials.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical membrane materials. Specifically, it relates to an antibacterial and high-temperature resistant medical membrane and a preparation method thereof. Background Art

[0002] With the continuous development of science and technology and the continuous improvement of thin film technology, its application fields are very broad. For example, it is involved in fields such as glass, metal, and aerospace. At present, thin films have gradually penetrated into the medical field. Medical membranes belong to a type of polymer material and are a kind of sanitary protection equipment used during hospital surgeries. Medical membranes play a crucial role in surgical operations. It can not only be used as a medical skin healing membrane and wound dressing to repair minor abrasions, small-area first- and second-degree burns, and smaller wounds, protect incisions during surgery, and prevent and treat chapped skin and pressure sores. Based on the application environment, there are very strict requirements for the cleanliness and performance of medical membranes.

[0003] Common medical membranes on the market are mainly divided into polyethylene, polyvinyl chloride, polyvinyl chloride, and polypropylene according to the base material. These thin film materials do not have degradable properties and cause relatively large pollution to the environment. Degradable and environmentally friendly medical membranes are new environmentally friendly products developed in developed countries such as Europe and the United States in recent years, aiming to avoid pollution and cross-infection between medical staff and patients.

[0004] Common degradable thin film base materials are polyvinyl alcohol materials, abbreviated as PVA. Natural polyvinyl alcohol materials have advantages such as biodegradability and non-toxicity when used in medical membranes. However, single polyvinyl alcohol materials do not have antibacterial properties and are prone to the growth of bacteria and other microorganisms on the surface, causing bacterial infections in patients and affecting the use safety of medical membranes. Moreover, in the medical field, due to some applications involving high temperatures, there are special requirements for the high-temperature resistance of the membrane. Polyvinyl alcohol turns color and becomes brittle when heated in air above 100°C, undergoes dehydration etherification when heated to 160 - 170°C, loses solubility, and starts to decompose when heated to 200°C. Therefore, based on the above problems, there is an urgent need to invent a polyvinyl alcohol medical membrane with antibacterial and high-temperature resistance properties to meet the higher requirements in the technical field of medical membrane materials. Summary of the Invention

[0005] The purpose of the present invention is to overcome the defects of the prior art and provide an antibacterial and high-temperature resistant medical membrane and a preparation method thereof.

[0006] The purpose of the present invention can be achieved by the following technical solutions:

[0007] A preparation method of an antibacterial and high-temperature resistant medical membrane includes the following steps:

[0008] Mix polyvinyl alcohol, deionized water, glutaraldehyde aqueous solution (crosslinking agent), multi-functional antibacterial agent, N,N-dimethylformamide, pregelatinized corn starch, and pretreated xanthan gum, heat to 50 - 80 °C, stir for 4 - 8 h, then pour the solution onto a glass plate to form a film by casting, and then place it in an oven at 50 °C for drying for 12 h. Put the dried film into distilled water, soak and wash to remove the residual solvent, and obtain a medical film with antibacterial and high-temperature resistance.

[0009] Furthermore, the dosage ratio of polyvinyl alcohol, deionized water, glutaraldehyde aqueous solution, multi-functional antibacterial agent, N,N-dimethylformamide, pregelatinized corn starch, and pretreated xanthan gum is 40 - 60 g: 200 - 300 mL: 10 - 20 mL: 5 - 15 g: 100 - 200 mL: 12 - 18 g: 6 - 12 g.

[0010] Furthermore, the mass fraction of the glutaraldehyde aqueous solution is 10 - 18%.

[0011] Corn starch has many hydroxyl groups and good solubility. Pregelatinized corn starch has a fluffy porous structure, making it have good water retention and thickening properties; xanthan gum is an extracellular polysaccharide of microorganisms, has good water absorption performance, can adsorb and block the penetration of water molecules, thereby reducing the erosion and damage of water to the polyvinyl alcohol medical film and improving the water resistance of the film; moreover, corn starch, xanthan gum and polyvinyl alcohol have a synergistic hydrogen bond interaction, can form a stable entangled network, making the prepared film have better heat resistance and mechanical strength.

[0012] Furthermore, the pretreated xanthan gum is prepared by the following steps:

[0013] Add xanthan gum and deionized water into a flask, stir at room temperature. After stirring for 30 min, add dilute hydrochloric acid to adjust the pH to 3, heat to 90 °C, stir for 4 h and then dialyze to remove the remaining dilute hydrochloric acid, and freeze-dry to obtain pretreated xanthan gum.

[0014] Furthermore, the dosage ratio of xanthan gum to deionized water is 10 g: 200 mL.

[0015] Furthermore, the multi-functional antibacterial agent is prepared by the following steps:

[0016] S1. Add 2-hydrazinoethanol, diethyl carbonate and sodium methoxide into a three-necked flask, control the reaction temperature at 80 °C, keep the temperature for 1 h for the reaction. After the reaction is completed, cool to precipitate a solid, filter by suction, and reserve the obtained dry solid. After the solvent is removed by rotary evaporation of the filtrate, column chromatography separation (the volume ratio of methanol to dichloromethane is 1:40) is used to obtain a white solid. Then, the dry solid and the white solid are mixed and stirred with ether for 10 min, and then filtered to obtain 3-amino-2-oxazolidinone; the dosage ratio of 2-hydrazinoethanol, diethyl carbonate, sodium methoxide, and ether is 7.7 g:11.8 g:0.2 g:50 mL;

[0017] 2-Hydrazinoethanol reacts with diethyl carbonate to form 3-amino-2-oxazolidinone; the specific reaction process is as follows:

[0018]

[0019] S2. Place a three-necked round-bottom flask equipped with a thermometer, a stirrer and a reflux condenser in a water bath. Mix 3-bromo-1,2-propanediol and N,N-dimethylformamide (DMF) and stir. While stirring, add 5-chloro-2-methylisothiazol-3-one (CMIT). After stirring evenly, control the temperature at 85 °C and carry out a condensation reflux reaction for 7 h. After the reaction is completed, remove the solvent by distillation under reduced pressure, wash with acetone 2-3 times, and dry under vacuum to obtain an intermediate; the dosage ratio of 3-bromo-1,2-propanediol, N,N-dimethylformamide, and 5-chloro-2-methylisothiazol-3-one is 15.3 g:100 mL:14.8 g;

[0020] 3-Bromo-1,2-propanediol and 5-chloro-2-methylisothiazol-3-one undergo a quaternization reaction to obtain an intermediate; the specific reaction is as follows:

[0021]

[0022] S3. In a three-necked flask equipped with a stirring device, mix the intermediate and N,N-dimethylformamide, turn on the stirrer, and sequentially add dibutyltin oxide (catalyst), potassium carbonate and 3-amino-2-oxazolidinone. Slowly raise the temperature to 65 °C and keep the temperature for 6 h for the reaction. After the reaction is completed, distill under reduced pressure, and then purify by column chromatography (the eluent uses a mixed solvent of methanol / ethyl acetate, and the volume ratio of the two is 8:3). Rotary evaporate to remove the eluent to obtain a multi-effect antibacterial agent; the dosage ratio of the intermediate, N,N-dimethylformamide, dibutyltin oxide, potassium carbonate, and 3-amino-2-oxazolidinone is 22.4 g:100 mL:0.3 g:5.3 g:10.2 g;

[0023] Under the catalysis of dibutyltin oxide, the intermediate undergoes nucleophilic substitution with 3-amino-2-oxazolidinone, and potassium carbonate removes the hydrogen chloride generated in the reaction to obtain a multi-functional antibacterial agent; the specific reaction is as follows:

[0024]

[0025] The multi-functional antibacterial agent prepared by the present invention contains isothiazolinone, quaternary ammonium salt, oxazolidinone and hydroxyl structure. Among them, isothiazolinone has excellent properties such as strong antibacterial ability, environmental safety and broad antibacterial spectrum. It forms a disulfide bond with the sulfhydryl group on cysteine in the pathogenic bacteria protein through the key active site on the heterocyclic ring, thereby inactivating the protein to achieve the purpose of sterilization, and can improve the antibacterial performance of the polyvinyl alcohol matrix to a certain extent. Moreover, the introduced quaternary ammonium salt ions will produce a strong electrostatic interaction with the negatively charged bacteria due to the positive charges they carry, and will have a strong adsorption effect on the bacteria, and can play a synergistic effect with isothiazolinone, significantly enhancing the antibacterial performance of the matrix. In addition, the introduced oxazolidinone has good heat resistance and can enhance the high-temperature resistance of the matrix to a certain extent. Finally, one end of the multi-functional antibacterial agent contains a hydroxyl group, which can crosslink with the matrix, enhancing the interaction force between the two, and greatly improving the migration resistance and exudation resistance of the multi-functional antibacterial agent, so that the multi-functional antibacterial agent can maintain its performance stably for a long time.

[0026] The beneficial effects of the present invention:

[0027] 1. The medical film prepared by the present invention adds pregelatinized corn starch and xanthan gum, which can produce a synergistic hydrogen bond interaction with the polyvinyl alcohol matrix, form a stable entanglement network, and endow the medical film with good water resistance, high temperature resistance, degradability and mechanical properties;

[0028] 2. The various groups in the prepared multi-functional antibacterial agent can play a synergistic role, greatly enhancing the antibacterial performance of the medical film. In addition, the multi-functional antibacterial agent can also enhance the high-temperature resistance of the medical film to a certain extent, and the performance is stable for a long time;

[0029] Therefore, the medical film prepared by the present invention has good water resistance, high mechanical strength, stable and efficient antibacterial performance and high-temperature resistance, and is environmentally friendly and degradable, and has important application value in the technical field of medical film materials. Specific embodiments

[0030] The following will combine the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. 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 belong to the protection scope of the present invention. Example 1

[0031] Preparation of Multi-Effect Antibacterial Agent:

[0032] S1. Add 7.7 g of 2-hydrazinoethanol, 11.8 g of diethyl carbonate and 0.2 g of sodium methoxide into a three-necked flask. Control the reaction temperature at 80 °C and keep the reaction for 1 h. After the reaction is completed, cool to precipitate a solid, filter by suction, and reserve the obtained dry solid. After the filtrate is rotary evaporated to remove the solvent, column chromatography separation (the volume ratio of methanol to dichloromethane is 1:40) is used to obtain a white solid. Then, the dry solid and the white solid are mixed and 50 mL of ether is added and stirred for 10 min, and then filtered to obtain 3-amino-2-oxazolidinone;

[0033] S2. Place a three-necked round-bottom flask equipped with a thermometer, a stirrer and a reflux condenser in a water bath. Mix 15.3 g of 3-bromo-1,2-propanediol and 100 mL of N,N-dimethylformamide and stir. While stirring, add 14.8 g of 5-chloro-2-methylisothiazolin-3-one. After stirring evenly, control the temperature at 85 °C and carry out a condensation reflux reaction for 7 h. After the reaction is completed, remove the solvent by vacuum distillation, wash twice with acetone, and dry under vacuum to obtain an intermediate;

[0034] S3. In a three-necked flask equipped with a stirring device, mix 22.4 g of the intermediate and 100 mL of N,N-dimethylformamide, turn on the stirrer, and successively add 0.3 g of dibutyltin oxide, 5.3 g of potassium carbonate and 10.2 g of 3-amino-2-oxazolidinone. Slowly raise the temperature to 65 °C and keep the reaction for 6 h. After the reaction is completed, carry out vacuum distillation, and then purify by column chromatography (the eluent is a mixed solvent of methanol / ethyl acetate, and the volume ratio of the two is 8:3). Rotary evaporate to remove the eluent to obtain the multi-effect antibacterial agent. Example 2

[0035] Preparation of Multi-Effect Antibacterial Agent:

[0036] S1. Add 15.4 g of 2-hydrazinoethanol, 23.6 g of diethyl carbonate and 0.4 g of sodium methoxide into a three-necked flask. Control the reaction temperature at 80 °C and keep the reaction for 1 h. After the reaction is completed, cool to precipitate a solid, filter by suction, and reserve the obtained dry solid. After the filtrate is rotary evaporated to remove the solvent, column chromatography separation (the volume ratio of methanol to dichloromethane is 1:40) is used to obtain a white solid. Then, the dry solid and the white solid are mixed and 100 mL of ether is added and stirred for 10 min, and then filtered to obtain 3-amino-2-oxazolidinone;

[0037] S2. Place a three-necked round-bottom flask equipped with a thermometer, a stirrer, and a reflux condenser in a water bath. Mix 30.6 g of 3-bromo-1,2-propanediol and 200 mL of N,N-dimethylformamide and stir. While stirring, add 29.6 g of 5-chloro-2-methylisothiazolin-3-one. After stirring evenly, control the temperature at 85 °C and carry out a condensation reflux reaction for 7 h. After the reaction is completed, remove the solvent by vacuum distillation, wash three times with acetone, and dry in vacuo to obtain an intermediate;

[0038] S3. In a three-necked flask equipped with a stirring device, mix 44.8 g of the intermediate and 200 mL of N,N-dimethylformamide, turn on the stirrer, and successively add 0.6 g of dibutyltin oxide, 10.6 g of potassium carbonate, and 20.4 g of 3-amino-2-oxazolidinone. Slowly heat up to 65 °C and hold the temperature for a reaction of 6 h. After the reaction is completed, carry out vacuum distillation, and then purify by column chromatography (the eluent uses a mixed solvent of methanol / ethyl acetate, and the volume ratio of the two is 8:3). Rotate and evaporate to remove the eluent to obtain a multi-effect antibacterial agent. Example 3

[0039] Prepare pretreated xanthan gum:

[0040] Add 10 g of xanthan gum and 200 mL of deionized water to a flask, stir at room temperature. After stirring for 30 min, add dilute hydrochloric acid (mass fraction 12%) to adjust the pH to 3, heat to 90 °C, stir for 4 h, then dialyze to remove the remaining dilute hydrochloric acid, and freeze-dry to obtain pretreated xanthan gum. Example 4

[0041] Mix 40 g of polyvinyl alcohol, 200 mL of deionized water, 10 mL of glutaraldehyde aqueous solution (mass fraction 10 - 18%), 5 g of the multi-effect antibacterial agent prepared in Example 1, 100 mL of N,N-dimethylformamide, 12 g of gelatinized corn starch, and 6 g of the pretreated xanthan gum prepared in Example 3, heat to 50 °C, stir for 4 h, then pour the solution onto a glass plate to form a film by casting, and then place it in an oven at 50 °C to dry for 12 h. Put the dried film into distilled water, immerse and wash to remove the residual solvent to obtain an antibacterial and high-temperature resistant medical film. Example 5

[0042] Mix 50 g of polyvinyl alcohol, 250 mL of deionized water, 15 mL of glutaraldehyde aqueous solution (mass fraction 10 - 18%), 10 g of the multi-effect antibacterial agent prepared in Example 2, 150 mL of N,N-dimethylformamide, 15 g of gelatinized corn starch, and 9 g of the pretreated xanthan gum prepared in Example 3, heat to 65 °C, stir for 5 h, then pour the solution onto a glass plate to form a film by casting, and then place it in an oven at 50 °C to dry for 12 h. Put the dried film into distilled water, immerse and wash to remove the residual solvent to obtain an antibacterial and high-temperature resistant medical film. Example 6

[0043] Mix 60 g of polyvinyl alcohol, 300 mL of deionized water, 20 mL of glutaraldehyde aqueous solution (mass fraction 10 - 18%), 15 g of the multi - effect antibacterial agent prepared in Example 2, 200 mL of N,N - dimethylformamide, 18 g of gelatinized corn starch, and 12 g of the pretreated xanthan gum prepared in Example 3. Heat to 80 °C and stir for 8 h. Then pour the solution onto a glass plate to cast a film, and then place it in an oven at 50 °C to dry for 12 h. Put the dried film into distilled water, soak and wash to remove the residual solvent to obtain an antibacterial and high - temperature - resistant medical film.

[0044] Comparative Example 1

[0045] Replace the multi - effect antibacterial agent in Example 6 with a commercially available antibacterial agent of the same mass, and the remaining steps are the same as in Example 6 to make a film.

[0046] Comparative Example 2

[0047] Use a commercially available polyvinyl alcohol film.

[0048] Make the films prepared in Examples 4 - 6 and Comparative Examples 1 - 2 into corresponding shapes according to different test standards, and conduct the following performance tests:

[0049] Determine the biodegradation rate according to the national standard GB / T 19811 - 2005;

[0050] Determine the water resistance of the specimen according to the national standard GB / T 1034 - 1998 "Test Method for Water Absorption of Plastics";

[0051] Determine the tensile properties of the specimen before and after 72 h in an environment of 180 °C according to the national standard GB / T 1040 - 2006 "Determination of Tensile Properties of Plastics";

[0052] According to the national standard GB / T 31402 - 2015 "Test Method for Antibacterial Properties of Plastic Surfaces", and using the film - sticking method, detect the inhibitory effects on Escherichia coli and Staphylococcus aureus; the method is as follows: Inoculate Escherichia coli or Staphylococcus aureus on a plate medium, cover the film and store for 24 hours, and then conduct viable bacteria culture; compare the parallel experimental results of the blank sample to obtain the antibacterial rate of the specimen;

[0053] Determine the antibacterial rate of the specimen after being placed at room temperature for 180 d using the same test standard;

[0054] The measured results are shown in the following table:

[0055]

[0056] As can be seen from the above table, the antibacterial property and high-temperature resistance of the medical film prepared by the present invention are higher than those of the comparative example, and it has good water resistance, high mechanical strength, and biodegradable property. The addition of the multi-effect antibacterial agent has little influence on the mechanical properties of the medical film, and it has important application value in the technical field of medical film materials.

[0057] In the description of the specification, the description with reference to terms such as "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.

[0058] The above content is only an example and illustration of the present invention. Those skilled in the art of the present technology can make various modifications or supplements to the described specific embodiments or use similar methods for substitution, as long as they do not deviate from the invention or exceed the scope defined by the claims of the present invention, they should fall within the protection scope of the present invention.

Claims

1. A preparation method of a medical film with antibacterial and high-temperature resistance, characterized in that, It includes the following steps: Mix polyvinyl alcohol, deionized water, aqueous glutaraldehyde solution, multi-effect antibacterial agent, N,N-dimethylformamide, pre-gelatinized corn starch and pretreated xanthan gum, heat to 50-80 °C, stir for 4-8 h, then pour the solution onto a glass plate to cast a film, dry it, put the dried film into distilled water, soak and wash to obtain a medical film with antibacterial and high-temperature resistance; Among them, the multi-effect antibacterial agent is prepared through the following steps: S1. Add 2-hydrazinoethanol, diethyl carbonate and sodium methoxide into a three-necked flask, react at 80 °C for 1 h. After the reaction is completed, cool it and filter by suction. Reserve the obtained dry solid. After the solvent is removed by rotary evaporation of the filtrate, column chromatography is used for separation to obtain a white solid. Then mix the dry solid with the white solid, add ether and stir for 10 min, filter to obtain 3-amino-2-oxazolidinone; S2. Mix 3-bromo-1,2-propanediol and N,N-dimethylformamide and stir. While stirring, add 5-chloro-2-methylisothiazolin-3-one. After stirring evenly, react at 85 °C for 7 h. After the reaction is completed, perform vacuum distillation, washing, and vacuum drying to obtain an intermediate; S3. Mix the intermediate and N,N-dimethylformamide, start the stirrer, and sequentially add dibutyltin oxide, potassium carbonate and 3-amino-2-oxazolidinone. React at 65 °C for 6 h. After the reaction is completed, perform vacuum distillation, purification by column chromatography, and rotary evaporation to obtain the multi-effect antibacterial agent; Among them, the pretreated xanthan gum is prepared through the following steps: Stir xanthan gum and deionized water at room temperature. After stirring for 30 min, add dilute hydrochloric acid to adjust the pH to 3, heat to 90 °C, stir for 4 h, then dialyze and freeze-dry to obtain the pretreated xanthan gum; Among them, the dosage ratio of polyvinyl alcohol, deionized water, aqueous glutaraldehyde solution, multi-effect antibacterial agent, N,N-dimethylformamide, pre-gelatinized corn starch, and pretreated xanthan gum is 40-60 g: 200-300 mL: 10-20 mL: 5-15 g: 100-200 mL: 12-18 g: 6-12 g.

2. The preparation method of a medical film with antibacterial and high-temperature resistance according to claim 1, characterized in that, In step S1, the dosage ratio of 2-hydrazinoethanol, diethyl carbonate, sodium methoxide, and ether is 7.7 g: 11.8 g: 0.2 g: 50 mL.

3. The preparation method of a medical film with antibacterial and high-temperature resistance according to claim 1, characterized in that, In step S2, the dosage ratio of 3-bromo-1,2-propanediol, N,N-dimethylformamide, and 5-chloro-2-methylisothiazolin-3-one is 15.3 g: 100 mL: 14.8 g.

4. The preparation method of an antibacterial and high-temperature resistant medical film according to claim 1, characterized in that, In step S3, the dosage ratio of the intermediate, N,N-dimethylformamide, dibutyltin oxide, potassium carbonate, and 3-amino-2-oxazolidinone is 22.4 g: 100 mL: 0.3 g: 5.3 g: 10.2 g.

5. A medical film with antibacterial and high-temperature resistance, characterized in that, Prepared by the method according to any one of claims 1-4.

Images