An irradiation grafting modified fiber membrane dressing and a preparation method thereof

Abstract

The application belongs to the technical field of fiber membrane dressings, and particularly relates to an irradiation grafting modified fiber membrane dressing and a preparation method thereof. A novel functional monomer is prepared by taking 3-chloro-2-hydroxypropyl methacrylate and 4-pyridine acetic acid as starting raw materials, introducing a pyridine group through an esterification reaction, and then introducing a quaternary ammonium salt group through a quaternary ammonium reaction. Then, through precise control of irradiation dose, time and other process parameters by using a co-irradiation technology, a controllable cross-linking reaction of the functional monomer, acrylic acid and carboxymethyl chitosan on the surface of the fiber membrane material is successfully realized. The three-dimensional network structure of the membrane material is optimized, and the chemical properties and physical morphology of the material surface are significantly improved, so that the mechanical strength is maintained while the high swelling property, antibacterial property and transdermal absorption performance are synergistically optimized.

Description

Technical Field

[0001] This invention belongs to the field of fiber membrane dressing technology, specifically relating to an irradiation grafted modified fiber membrane dressing and its preparation method. Background Technology

[0002] Drug delivery is an effective means of treating a variety of human diseases. Drug carrier materials, as an important component of drug delivery systems, are a major factor affecting drug efficacy. Therefore, constructing suitable drug delivery carriers is crucial. Fiber membrane dressings are a widely used carrier material in drug delivery systems, playing a vital role, especially in wound healing and local drug delivery. Their unique structure and properties make them an ideal choice for constructing drug delivery carriers.

[0003] Patent application CN202010373990.9 provides a method for preparing a nanofiber membrane wound dressing. First, chitosan is modified with gingerone to alter its ordered structure, reduce intermolecular hydrogen bonding, and improve its moisturizing and swelling properties. Then, the modified chitosan is mixed with silk fibroin to prepare a spinning solution. The nanofiber membrane wound dressing is then prepared using electrospinning technology. Finally, the nanofiber membrane is modified with modifiers such as tyrosine and hyaluronic acid to increase its protein adsorption capacity and promote wound healing. Although the mixture of modified chitosan and silk fibroin improves the swelling and moisturizing properties of the nanofiber membrane, its mechanical properties are still insufficient. In practical applications, the dressing needs to possess a certain mechanical strength to withstand the stretching and friction during daily activities. Furthermore, preventing infection is crucial during wound healing; a lack of antibacterial properties can lead to wound infection and delay healing. Patent application CN202010487233.4 discloses a method for preparing a high-strength nanofiber membrane wound dressing. Under photostimulation, the photosensitizer graphene oxide (GO) and indocyanine green (ICG) undergo a photothermal effect, allowing the encapsulated drug doxorubicin to be released in a controlled manner based on temperature. The GO@ICG / PCM / CA / PCL nanofiber membrane prepared by electrospinning technology has the potential for sustained and controlled drug release and is suitable for wound dressings. This dressing has a high specific surface area and porous characteristics, good air permeability, high biocompatibility, significantly improved mechanical strength (elongation at break increased from 6% to 12%), enhanced hydrophilicity, stable photothermal conversion performance, and sensitive near-infrared responsiveness. Despite these advantages, its transdermal absorption performance is insufficient. Specifically, although the hydrophilicity of the nanofiber membrane is enhanced, its transdermal absorption efficiency remains low, failing to effectively promote drug penetration through the skin barrier into deeper tissues. In addition, although the photothermal effect of dressings can trigger drug release, in practical applications, the penetration depth of light stimulation is limited, which may not be able to fully act on deep wounds, affecting the effective release and absorption of drugs.

[0004] Low-energy electron beam (EBI) irradiation technology, as a non-thermal processing technique, offers significant advantages, effectively avoiding the thermal degradation of cellulose and its membrane materials caused by high temperatures in traditional thermal processing techniques. By directly applying accelerated high-energy electrons to the material, EBI irradiation technology can rapidly initiate the material's active system without introducing high temperatures, achieving reactions such as crosslinking, grafting, polymerization, pyrolysis, and curing, thereby functionalizing cellulose and its membrane materials. For example, in the preparation of wound dressings, EBI irradiation technology can be used to modify cellulose membrane materials, improving their mechanical properties, hydrophilicity, and drug release performance, thus producing fiber membrane dressings with superior overall performance. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide an irradiation-grafted modified fiber membrane dressing and its preparation method. First, novel functional monomers are prepared by introducing pyridine and quaternary ammonium salt groups. Then, using co-irradiation technology, and by precisely controlling process parameters such as irradiation dose and time, a controllable cross-linking reaction of the functional monomers, acrylic acid, and carboxymethyl chitosan on the surface of the fiber membrane material is successfully achieved. This invention optimizes the three-dimensional network structure of the membrane material and significantly improves the chemical properties and physical morphology of the material surface, thereby systematically enhancing the overall performance of the fiber membrane dressing.

[0006] The technical solution adopted by the present invention to achieve the above objectives is as follows:

[0007] A method for preparing an irradiated grafted modified fiber membrane dressing includes the following steps:

[0008] Step S1: Mix 3-chloro-2-hydroxypropyl methacrylate, N,N-dimethylformamide and p-toluenesulfonic acid evenly, raise the temperature to 55-65℃ under stirring, add 4-pyridineacetic acid, react for 6-10h, cool to room temperature, extract the organic phase, remove the extraction solvent and dry.

[0009] Step S2: Under a nitrogen atmosphere and stirring conditions, the product obtained in step S1 is dispersed in anhydrous ethanol, the temperature is raised to 70-80℃, potassium iodide and triethylamine are added, the reaction is carried out for 15-20 hours, and after cooling to room temperature, it is purified to obtain the functional monomer.

[0010] Step S3: At room temperature, mix carboxymethyl chitosan and deionized water evenly and stir for 40-60 minutes. Then add acrylic acid, functional monomer and crosslinking agent in sequence and continue stirring for 10-30 minutes to obtain a mixed solution. Immerse the pretreated fiber membrane in the mixed solution and place it in the irradiation reaction system for irradiation treatment. After irradiation, take out the fiber membrane, clean and dry it to obtain the final product.

[0011] The preparation route for the functional monomers is as follows:

[0012]

[0013] This invention uses 3-chloro-2-hydroxypropyl methacrylate and 4-pyridineacetic acid as starting materials. Under the catalysis of p-toluenesulfonic acid, an esterification reaction occurs. Then, under the action of potassium iodide, a quaternization reaction is further carried out with triethylamine to obtain a functional monomer. Quaternary ammonium salt groups, pyridine groups, and acrylate groups are introduced into the molecular structure of the functional monomer using a two-step method. Finally, using the functional monomer, acrylic acid, and carboxymethyl chitosan as raw materials, a cross-linking polymerization reaction is carried out on the surface of the fiber membrane material through co-irradiation to obtain an irradiated grafted modified fiber membrane dressing.

[0014] To reduce byproducts and improve reaction efficiency during the preparation of functional monomers, the molar ratio of 3-chloro-2-hydroxypropyl methacrylate, p-toluenesulfonic acid, and 4-pyridineacetic acid in step S1 is 1.1:0.01-0.02:0.8-1.0, and the mass-to-volume ratio of 3-chloro-2-hydroxypropyl methacrylate and N,N-dimethylformamide is 0.15-0.20 g / mL; the molar ratio of the product obtained in step S1, potassium iodide, and triethylamine in step S2 is 0.9:0.22-0.28:1.2-1.4, and the amount of the product obtained in step S1 added to the anhydrous ethanol is 0.2-0.4 g / mL.

[0015] Considering that the raw material ratio has a significant impact on the viscosity of the reaction system, and that different monomer concentrations also affect the grafting rate and thus the product performance, the following optimization was performed: the mass ratio of acrylic acid, functional monomer, and carboxymethyl chitosan in step S3 is 25:8-12:0.5-1.5, and the volume fraction of acrylic acid in the mixed solution is 5-10%.

[0016] Since the concentration of the crosslinking agent directly affects the grafting rate, and the crosslinking agent has a saturation concentration, the crosslinking agent is N,N'-methylenebisacrylamide, and the mass percentage of the crosslinking agent in the mixed solution is 0.25-0.75%.

[0017] Preferably, the pretreatment process of the fiber membrane material in step S3 is as follows: ultrasonic cleaning is performed sequentially with anhydrous ethanol and water, followed by drying, to obtain the ultrasonically cleaned pretreated fiber membrane material, which removes impurities from the membrane surface and increases the surface roughness and active sites.

[0018] Considering that the grafting rate increases with the increase of the irradiation dose, and tends to stabilize after the irradiation dose reaches a certain amount, the specific steps of the irradiation treatment in step S3 are as follows: under a nitrogen atmosphere, the irradiation energy is set to 160-200keV, the irradiation dose is 40-70kGy, the irradiation temperature is room temperature, and the irradiation time is 5min.

[0019] In the preparation of functional monomers, the quaternary ammonium salt groups introduced through the reaction in this invention possess strong hydrophilicity, attracting water molecules into the membrane. Acrylic acid contains carboxyl groups, and carboxymethyl chitosan also contains a large number of hydrophilic groups. These hydrophilic groups can form hydrogen bonds with water, increasing the water absorption capacity of the fiber membrane and thus enhancing the swelling performance of the fiber membrane dressing. In addition, the large number of hydrophilic groups on the surface of the fiber membrane can also increase the surface energy of the membrane material, making it easier for water to spread on the membrane surface, thereby improving the wettability of the fiber membrane dressing. Carboxymethyl chitosan, as a natural polymer material, has good film-forming properties and mechanical properties. It works synergistically with functional monomers and acrylic acid to form a three-dimensional network structure on the surface of the fiber membrane through cross-linking polymerization, enhancing the interaction between fibers and improving the mechanical properties of the fiber membrane dressing. Furthermore, the pyridine groups introduced through the reaction in the functional monomers can also enhance the internal interaction forces of the fiber membrane through hydrogen bonding, π-π stacking, etc., further improving the mechanical properties of the fiber membrane dressing. The quaternary ammonium salt and pyridine groups in the functional monomers possess antibacterial activity. They can disrupt the integrity of bacterial cell membranes through interaction, causing intracellular substances to leak out, thereby achieving an antibacterial effect. Carboxymethyl chitosan also has certain antibacterial properties, and its synergistic effect with the functional monomers further enhances the antibacterial effect of the fiber membrane dressing. The pyridine groups and acrylate structures introduced into the functional monomers can interact with the lipid layer on the skin surface, increasing the affinity of the fiber membrane dressing to the skin. Carboxymethyl chitosan has good biocompatibility and permeation-enhancing effects. The affinity of the pyridine groups and acrylate structures with the skin lipid layer, combined with the permeation-enhancing properties of carboxymethyl chitosan, further promotes the delivery of active drug molecules and significantly enhances the transdermal absorption capacity of the fiber membrane dressing.

[0020] The irradiated grafted modified fiber membrane dressing prepared by the above method exhibits enhanced overall performance under electron beam irradiation. The high energy of the electron beam triggers free radical reactions, promoting cross-linking polymerization on the fiber surface. Simultaneously, by controlling the electron beam energy, the fiber's skeletal structure remains largely intact during irradiation, maintaining a high loading rate and large specific surface area. Active pharmaceutical ingredients can adhere to or embed into the fiber network through physical adsorption or chemical bonding, and are slowly released when needed, fully realizing their functionality.

[0021] This invention utilizes co-irradiation to initiate a cross-linking polymerization reaction between functional monomers, acrylic acid, and carboxymethyl chitosan on the surface of a fiber membrane, forming a three-dimensional network structure. When exposed to water, the hydrophilic groups within this structure attract water molecules, allowing them to penetrate the network. Simultaneously, by controlling process parameters and regulating the cross-linking density, the fiber membrane dressing maintains structural stability while exhibiting high swelling capacity. The irradiated grafted membrane surface forms a hydrophilic coating, further improving the wettability of the fiber membrane dressing. This improvement facilitates better contact between the dressing and the skin surface, enhancing user comfort. Furthermore, the three-dimensional network structure formed on the fiber membrane surface enhances the mechanical properties of the fiber membrane dressing. The use of the cross-linking agent N,N'-methylenebisacrylamide further consolidates this network structure, improving the overall mechanical properties of the fiber membrane dressing. The irradiation grafting reaction creates a coating with specific structure and properties on the surface of the fiber membrane material, optimizing the network structure and surface properties of the membrane material. This facilitates the penetration of drugs or bioactive substances from the surface of the fiber membrane dressing into skin tissue, further improving the transdermal absorption performance of the dressing.

[0022] In summary, this invention significantly improves the swelling properties, wettability, mechanical properties, antibacterial properties, and transdermal absorption properties of fiber membrane dressings through precise process control and synergistic effects between raw materials. Attached Figure Description

[0023] Figure 1 SEM image of the ungrafted modified fiber membrane material;

[0024] Figure 2 SEM image of the fiber membrane dressing prepared in Example 1;

[0025] Figure 3 SEM image of the fiber membrane dressing prepared in Example 2;

[0026] Figure 4 Here is a SEM image of the fiber membrane dressing prepared in Example 3;

[0027] Figure 5 SEM image of the fiber membrane dressing prepared in Example 4;

[0028] Figure 6 SEM image of the fiber membrane dressing prepared in Comparative Example 3;

[0029] Figure 7 This is a test diagram of the contact angle of the fiber membrane dressing. Detailed Implementation

[0030] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the embodiments of this application. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application. The raw materials used in the following embodiments are all common commercially available products.

[0031] Example 1

[0032] A method for preparing an irradiated grafted modified fiber membrane dressing includes the following steps:

[0033] Step S1: Mix 3-chloro-2-hydroxypropyl methacrylate, N,N-dimethylformamide, and p-toluenesulfonic acid evenly. Heat the mixture to 60°C while stirring at 150 rpm, then add 4-pyridineacetic acid. React for 8 hours, allow to cool naturally to room temperature, and extract with ethyl acetate and deionized water (V / V ratio of N,N-dimethylformamide, deionized water, and ethyl acetate is 1:1:2). Collect the organic phase, remove ethyl acetate by rotary evaporation, and dry under vacuum at 60°C for 12 hours. The molar ratio of 3-chloro-2-hydroxypropyl methacrylate, p-toluenesulfonic acid, and 4-pyridineacetic acid is 1.1:0.015:0.9; the mass-to-volume ratio of 3-chloro-2-hydroxypropyl methacrylate to N,N-dimethylformamide is 0.17 g / mL.

[0034] Step S2: Under a nitrogen atmosphere and stirring at 150 rpm, disperse the product obtained in step S1 into anhydrous ethanol, raise the temperature to 75°C, and then add potassium iodide and triethylamine sequentially. Reflux for 18 hours, cool naturally to room temperature, filter, collect the filtrate, remove anhydrous ethanol by vacuum distillation, and then extract with diethyl ether and deionized water (volume ratio of anhydrous ethanol, deionized water, and diethyl ether is 2:1:2). Collect the organic phase, remove diethyl ether by rotary evaporation, and dry under vacuum at 40°C for 24 hours to obtain the functional monomer. The molar ratio of the product obtained in step S1, potassium iodide, and triethylamine is 0.9:0.25:1.3 (the amount of substance is calculated based on the given molecular weight of the target product). The amount of the product obtained in step S1 added to the anhydrous ethanol is 0.3 g / mL.

[0035] Step S3: At room temperature, carboxymethyl chitosan (99% effective ingredient content, purchased from Xi'an Tianzheng Pharmaceutical Excipients Co., Ltd.) is mixed evenly with deionized water and stirred for 50 minutes. Then, acrylic acid, functional monomers, and crosslinking agents are added sequentially, and stirring is continued for 20 minutes to obtain a mixed solution. The pretreated fiber membrane is immersed in the mixed solution and allowed to stand for 5 minutes. Then, it is placed in the irradiation reaction system for irradiation treatment. After irradiation, the fiber membrane is removed from the mixed solution, washed with deionized water at least three times, and vacuum dried at 60°C. The mixture is dried to constant weight to obtain the final product; wherein the mass ratio of acrylic acid, functional monomer, and carboxymethyl chitosan is 25:10:1, the volume fraction of acrylic acid in the mixed solution is 7.5%, the crosslinking agent is N,N'-methylenebisacrylamide, and the mass percentage of the crosslinking agent in the mixed solution is 0.5%; the pretreatment process of the fiber membrane material is as follows: ultrasonic cleaning is performed sequentially with anhydrous ethanol and water, with an ultrasonic power of 50W and an ultrasonic time of 5min for each step, followed by vacuum drying at 60℃ to constant weight; the fiber membrane material is a cellulose membrane material with a density of 30g / m³. 2 The thickness is 0.3 mm and it was purchased from Shanghai Wenfang Industrial Co., Ltd.; the specific steps of the irradiation treatment are as follows: under a nitrogen atmosphere, according to the bath ratio of solution volume to membrane mass of 30, electron beam irradiation (EBI) technology is used, the irradiation energy is set to 180 keV, the irradiation dose is 60 kGy, the irradiation temperature is room temperature, and the irradiation time is 5 min.

[0036] The grafting rate of the fiber membrane dressing prepared in this embodiment was determined. First, a certain amount of fiber membrane sample was accurately weighed as the original sample and its weight was recorded as W0. Then, the fiber membrane was subjected to irradiation grafting modification. After the reaction was completed, the fiber membrane was thoroughly washed and dried to remove unreacted substances and impurities, resulting in the grafted fiber membrane dressing. It was then accurately weighed again and its weight was recorded as W1. The grafting rate was calculated using the formula: G(%) = (W1 - W0) / W0 × 100%. According to the above formula, the grafting rate of the fiber membrane dressing prepared in this embodiment was 46.6%.

[0037] Example 2

[0038] A method for preparing an irradiated grafted modified fiber membrane dressing includes the following steps:

[0039] Step S1: Mix 3-chloro-2-hydroxypropyl methacrylate, N,N-dimethylformamide, and p-toluenesulfonic acid evenly. Heat the mixture to 65°C while stirring at 150 rpm, then add 4-pyridineacetic acid. React for 6 hours, allow to cool naturally to room temperature, and extract with ethyl acetate and deionized water (V / V ratio of N,N-dimethylformamide, deionized water, and ethyl acetate is 1:1:2). Collect the organic phase, remove ethyl acetate by rotary evaporation, and dry under vacuum at 60°C for 12 hours. The molar ratio of 3-chloro-2-hydroxypropyl methacrylate, p-toluenesulfonic acid, and 4-pyridineacetic acid is 1.1:0.015:0.9; the mass-to-volume ratio of 3-chloro-2-hydroxypropyl methacrylate to N,N-dimethylformamide is 0.17 g / mL.

[0040] Step S2: Under a nitrogen atmosphere and stirring at 150 rpm, disperse the product obtained in step S1 into anhydrous ethanol, raise the temperature to 80°C, and then add potassium iodide and triethylamine sequentially. Reflux for 15 h, cool naturally to room temperature, filter, collect the filtrate, remove anhydrous ethanol by vacuum distillation, and then extract with diethyl ether and deionized water (volume ratio of anhydrous ethanol, deionized water, and diethyl ether is 2:1:2). Collect the organic phase, remove diethyl ether by rotary evaporation, and dry under vacuum at 40°C for 24 h to obtain the functional monomer. The molar ratio of the product obtained in step S1, potassium iodide, and triethylamine is 0.9:0.25:1.3 (the amount of substance is calculated based on the given molecular weight of the target product). The amount of the product obtained in step S1 added to the anhydrous ethanol is 0.3 g / mL.

[0041] Step S3: At room temperature, carboxymethyl chitosan (99% effective ingredient content, purchased from Xi'an Tianzheng Pharmaceutical Excipients Co., Ltd.) is mixed evenly with deionized water and stirred for 40 minutes. Then, acrylic acid, functional monomers, and crosslinking agents are added sequentially, and stirring is continued for 10 minutes to obtain a mixed solution. The pretreated fiber membrane is immersed in the mixed solution and allowed to stand for 5 minutes. Then, it is placed in the irradiation reaction system for irradiation treatment. After irradiation, the fiber membrane is removed from the mixed solution, washed with deionized water at least three times, and vacuum dried at 60°C. The mixture is dried to constant weight to obtain the final product; wherein the mass ratio of acrylic acid, functional monomer, and carboxymethyl chitosan is 25:10:1, the volume fraction of acrylic acid in the mixed solution is 7.5%, the crosslinking agent is N,N'-methylenebisacrylamide, and the mass percentage of the crosslinking agent in the mixed solution is 0.5%; the pretreatment process of the fiber membrane material is as follows: ultrasonic cleaning is performed sequentially with anhydrous ethanol and water, with an ultrasonic power of 50W and an ultrasonic time of 5min for each step, followed by vacuum drying at 60℃ to constant weight; the fiber membrane material is a cellulose membrane material with a density of 30g / m³. 2The thickness was 0.3 mm, purchased from Shanghai Wenfang Industrial Co., Ltd.; the specific steps of the irradiation treatment were as follows: under a nitrogen atmosphere, with a solution volume: membrane mass ratio of 30, electron beam irradiation (EBI) technology was used, with the irradiation energy set to 200 keV, the irradiation dose to 70 kGy, the irradiation temperature to room temperature, and the irradiation time to 5 min; the grafting rate of the fiber membrane dressing prepared in this embodiment was 48.1%.

[0042] Example 3

[0043] A method for preparing an irradiated grafted modified fiber membrane dressing includes the following steps:

[0044] Step S1: Mix 3-chloro-2-hydroxypropyl methacrylate, N,N-dimethylformamide, and p-toluenesulfonic acid evenly. Heat the mixture to 55°C while stirring at 150 rpm, then add 4-pyridineacetic acid. React for 10 hours, allow to cool naturally to room temperature, and extract with ethyl acetate and deionized water (V / V ratio of N,N-dimethylformamide, deionized water, and ethyl acetate is 1:1:2). Collect the organic phase, remove ethyl acetate by rotary evaporation, and dry under vacuum at 60°C for 12 hours. The molar ratio of 3-chloro-2-hydroxypropyl methacrylate, p-toluenesulfonic acid, and 4-pyridineacetic acid is 1.1:0.015:0.9; the mass-to-volume ratio of 3-chloro-2-hydroxypropyl methacrylate to N,N-dimethylformamide is 0.17 g / mL.

[0045] Step S2: Under a nitrogen atmosphere and stirring at 150 rpm, disperse the product obtained in step S1 into anhydrous ethanol, raise the temperature to 70°C, and then add potassium iodide and triethylamine sequentially. Reflux for 20 h, cool naturally to room temperature, filter, collect the filtrate, remove anhydrous ethanol by vacuum distillation, and then extract with diethyl ether and deionized water (volume ratio of anhydrous ethanol, deionized water, and diethyl ether is 2:1:2). Collect the organic phase, remove diethyl ether by rotary evaporation, and dry under vacuum at 40°C for 24 h to obtain the functional monomer. The molar ratio of the product obtained in step S1, potassium iodide, and triethylamine is 0.9:0.25:1.3 (the amount of substance is calculated based on the given molecular weight of the target product). The amount of the product obtained in step S1 added to the anhydrous ethanol is 0.3 g / mL.

[0046] Step S3: At room temperature, carboxymethyl chitosan (99% effective ingredient content, purchased from Xi'an Tianzheng Pharmaceutical Excipients Co., Ltd.) is mixed evenly with deionized water and stirred for 60 minutes. Then, acrylic acid, functional monomers, and crosslinking agents are added sequentially, and stirring is continued for 30 minutes to obtain a mixed solution. The pretreated fiber membrane is immersed in the mixed solution and allowed to stand for 5 minutes. Then, it is placed in the irradiation reaction system for irradiation treatment. After irradiation, the fiber membrane is removed from the mixed solution, washed with deionized water at least three times, and vacuum dried at 60°C. The mixture is dried to constant weight to obtain the final product; wherein the mass ratio of acrylic acid, functional monomer, and carboxymethyl chitosan is 25:10:1, the volume fraction of acrylic acid in the mixed solution is 7.5%, the crosslinking agent is N,N'-methylenebisacrylamide, and the mass percentage of the crosslinking agent in the mixed solution is 0.5%; the pretreatment process of the fiber membrane material is as follows: ultrasonic cleaning is performed sequentially with anhydrous ethanol and water, with an ultrasonic power of 50W and an ultrasonic time of 5min for each step, followed by vacuum drying at 60℃ to constant weight; the fiber membrane material is a cellulose membrane material with a density of 30g / m³. 2 The thickness was 0.3 mm, purchased from Shanghai Wenfang Industrial Co., Ltd.; the specific steps of the irradiation treatment were as follows: under a nitrogen atmosphere, with a solution volume: membrane mass ratio of 30, electron beam irradiation (EBI) technology was used, with the irradiation energy set to 160 keV, the irradiation dose to 40 kGy, the irradiation temperature to room temperature, and the irradiation time to 5 min; the grafting rate of the fiber membrane dressing prepared in this embodiment was 45.3%.

[0047] Example 4

[0048] A method for preparing an irradiated grafted modified fiber membrane dressing includes the following steps:

[0049] Step S1: Mix 3-chloro-2-hydroxypropyl methacrylate, N,N-dimethylformamide, and p-toluenesulfonic acid evenly. Heat the mixture to 60°C while stirring at 150 rpm, then add 4-pyridineacetic acid. React for 8 hours, allow to cool naturally to room temperature, and extract with ethyl acetate and deionized water (V / V ratio of N,N-dimethylformamide, deionized water, and ethyl acetate is 1:1:2). Collect the organic phase, remove ethyl acetate by rotary evaporation, and dry under vacuum at 60°C for 12 hours. The molar ratio of 3-chloro-2-hydroxypropyl methacrylate, p-toluenesulfonic acid, and 4-pyridineacetic acid is 1.1:0.02:1.0; the mass-to-volume ratio of 3-chloro-2-hydroxypropyl methacrylate to N,N-dimethylformamide is 0.17 g / mL.

[0050] Step S2: Under a nitrogen atmosphere and stirring at 150 rpm, disperse the product obtained in step S1 in anhydrous ethanol, raise the temperature to 75°C, and then add potassium iodide and triethylamine sequentially. Reflux for 18 hours, cool naturally to room temperature, filter, collect the filtrate, remove anhydrous ethanol by vacuum distillation, and then extract with diethyl ether and deionized water (volume ratio of anhydrous ethanol, deionized water, and diethyl ether is 2:1:2). Collect the organic phase, remove diethyl ether by rotary evaporation, and dry under vacuum at 40°C for 24 hours to obtain the functional monomer. The molar ratio of the product obtained in step S1, potassium iodide, and triethylamine is 0.9:0.28:1.4 (the amount of substance is calculated based on the given molecular weight of the target product). The amount of the product obtained in step S1 added to the anhydrous ethanol is 0.3 g / mL.

[0051] Step S3: At room temperature, carboxymethyl chitosan (99% effective ingredient content, purchased from Xi'an Tianzheng Pharmaceutical Excipients Co., Ltd.) is mixed evenly with deionized water and stirred for 50 minutes. Then, acrylic acid, functional monomers, and crosslinking agents are added sequentially, and stirring is continued for 30 minutes to obtain a mixed solution. The pretreated fiber membrane is immersed in the mixed solution and allowed to stand for 5 minutes. Then, it is placed in the irradiation reaction system for irradiation treatment. After irradiation, the fiber membrane is removed from the mixed solution, washed with deionized water at least three times, and vacuum dried at 60°C until… The solution is brought to constant weight; wherein the mass ratio of acrylic acid, functional monomer, and carboxymethyl chitosan is 25:12:1.5, the volume fraction of acrylic acid in the mixed solution is 10%, the crosslinking agent is N,N'-methylenebisacrylamide, and the mass percentage of the crosslinking agent in the mixed solution is 0.75%; the pretreatment process of the fiber membrane material is as follows: ultrasonic cleaning is performed sequentially with anhydrous ethanol and water, with an ultrasonic power of 50W and an ultrasonic time of 5min for each, followed by vacuum drying at 60℃ to constant weight. The fiber membrane material is a cellulose membrane material with a density of 30g / m³. 2 The thickness was 0.3 mm, purchased from Shanghai Wenfang Industrial Co., Ltd.; the specific steps of the irradiation treatment were as follows: under a nitrogen atmosphere, with a solution volume: membrane mass ratio of 30, electron beam irradiation (EBI) technology was used, with the irradiation energy set to 190 keV, the irradiation dose to 50 kGy, the irradiation temperature to room temperature, and the irradiation time to 5 min; the grafting rate of the fiber membrane dressing prepared in this embodiment was 47.0%.

[0052] Comparative Example 1

[0053] A method for preparing an irradiated grafted modified fiber membrane dressing, prepared according to the method described in Example 1, except that step S2 is omitted and the functional monomer in step S3 is replaced with the product obtained in step S1.

[0054] Comparative Example 2

[0055] A method for preparing an irradiated grafted modified fiber membrane dressing, prepared according to the method described in Example 1, except that steps S1 and S2 are omitted, and no functional monomer is added in step S3.

[0056] Comparative Example 3

[0057] A method for preparing an irradiated grafted modified fiber membrane dressing, prepared according to the method described in Example 1, except that steps S1 and S2 are omitted, and functional monomers and carboxymethyl chitosan are not added in step S3.

[0058] The fiber membrane dressings prepared in Examples 1-4 and Comparative Examples 1-3 were subjected to relevant performance tests.

[0059] The surface morphology of the fiber membrane material and fiber membrane dressing was evaluated using scanning electron microscopy (SEM, Phenom G2 Pro, USA). Bulk thin film samples were coated with gold in a sputtering coater (K575X turbine sputtering coater system - Emitech) to prevent pre-test charging effects. The results are as follows: Figure 1-6 As shown, where, Figure 1 This is a SEM image of the ungrafted modified fiber membrane material. Figure 2 This is a SEM image of the fiber membrane dressing prepared in Example 1. Figure 3 This is a SEM image of the fiber membrane dressing prepared in Example 2. Figure 4 This is a SEM image of the fiber membrane dressing prepared in Example 3. Figure 5 This is a SEM image of the fiber membrane dressing prepared in Example 4. Figure 6 The image shows a SEM image of the fiber membrane dressing prepared in Comparative Example 3. The results indicate that the fiber membrane sample before grafting modification (image) Figure 1 The fiber membrane dressings prepared in Examples 1-4 and Comparative Example 3 exhibit the shape of natural plant fibers, with a smooth surface and a network structure. Figure 2-6 The surface and gaps of the fiber were covered and filled with polymer molecules and cross-linked. The polymer molecules formed were clearly adhered to the fiber, indicating that under co-irradiation conditions, after being bombarded by electron beam, the fiber and raw materials such as acrylic acid and functional monomers underwent a cross-linking polymerization reaction, and the fiber skeleton structure was not significantly damaged. Among them, the fiber membrane dressing prepared in Comparative Example 3 maintained the corresponding network structure, but its fiber surface became rough and even showed obvious cracks.

[0060] The hydrophilicity and surface absorbency of the fiber membrane dressings prepared in Example 1 and Comparative Example 1 were evaluated using the WCA method. A droplet shape analyzer (DSA30S, Kruss GmbH, Germany) was used to measure the contact angle of the samples. The droplet volume was 2 μL, and the test conditions were 25°C and 60% relative humidity. By measuring the contact angle of the liquid on the surface of the modified fiber membrane material, information such as the wettability of the droplet on the material surface can be obtained, thus understanding the properties of the material surface. The results are as follows: Figure 7 As shown, where, Figure 7 (a) shows the water contact angle of the fiber membrane dressing prepared in Example 1. Figure 7 (b) The water contact angle of the fiber membrane dressing prepared in Comparative Example 1. Figure 7 It can be seen that the surface contact angles of the fiber membrane dressings prepared in Example 1 and Comparative Example 1 are 42.0° and 59.7°, respectively. The surface contact angle of the fiber membrane dressing prepared in Example 1 is lower, thus its wetting effect is better. This is because the introduction of quaternary ammonium salt groups into the copolymer molecules further increases the polarity of the fiber membrane dressing surface, thereby improving wettability.

[0061] Tensile tests were conducted using an MTS (E43.104) electronic universal testing machine to investigate the mechanical properties of the irradiated grafted modified fiber membrane dressing. For the tensile strength test, the entire film was cut into square standard specimens along the transverse and longitudinal directions, and the test was performed at a rate of 3 mm / min. Strain and stress were recorded using an extensometer (TST-1003) until the maximum breaking strength was reached. Each test was repeated three times, and the average value and standard deviation were obtained. By measuring the stress and strain data during the tensile process, the elastic modulus of the film could be calculated.

[0062] The swelling properties of the fiber membrane dressing were tested using a gravimetric method. The swelling effect of the sample in a PBS solution with a pH of 7.4 was measured at room temperature. First, the prepared fiber membrane dressing was cut into 5cm × 5cm pieces and dried to constant weight in an oven at 30℃. Then, it was immersed in PBS solution. The swollen fiber membrane material was removed from the PBS at different time intervals, and the surface moisture was gently wiped dry with filter paper. It was then weighed until the maximum swelling rate was reached (approximately 24 hours). The swelling rate (S) of the fiber membrane dressing was measured. R S (%) represents the increase relative to the initial mass of the sample, and the relevant formula is as follows: R (%) = (m1-m0) / m0×100%; where m0 is the initial mass of the sample and m1 is the mass of the sample after swelling.

[0063] This application uses representative Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) and employs the plate count method to determine the antibacterial activity of the prepared fiber membrane dressing.

[0064] Catechins were dissolved in a 75% ethanol aqueous solution (the mass-to-volume ratio of catechin to 75% ethanol aqueous solution was 20 mg / mL) to prepare a catechin solution. A fibrous membrane dressing (2 cm × 2 cm) was then immersed in the catechin solution and allowed to stand for 24 hours (the volume ratio of the catechin solution to the cellulose mass was 30). After immersion, the concentration of catechin in the remaining catechin solution was measured, and the mass of the remaining catechin was calculated. Based on the change in the mass of catechin before and after immersion, the drug loading rate of the fibrous membrane dressing was calculated. The immersed fibrous membrane dressing was then applied to an equal area of ​​rat skin for in vitro transdermal absorption experiments. A transdermal diffusion assay was performed using a PBS solution with a pH of 7.4 as the receiving medium. The experimental temperature was 36.5℃, and the experimental time was 24 hours. After 24 hours, an appropriate amount of the receiving medium was taken, the catechin concentration was measured, and an equal amount of fresh PBS buffer was added promptly to calculate the permeation rate.

[0065] The results of mechanical property tests, swelling property tests, antibacterial properties, drug loading rate, and transdermal absorption tests are shown in Table 1. All experiments were performed in triplicate. Data are presented as averages and statistically analyzed using Excel 2023 and SPSS 26.0 software.

[0066] Table 1. Performance test results of fiber membrane dressings

[0067]

[0068]

[0069] As shown in Table 1, the longitudinal elastic modulus of the fiber membrane dressings prepared in Examples 1-4 and Comparative Examples 1-3 is higher than that in the transverse elastic modulus. The fiber membrane dressings prepared in Examples 1-4 all exhibit excellent mechanical properties, with longitudinal elastic moduli ranging from 726.0 MPa to 819.2 MPa and transverse elastic moduli ranging from 638.7 MPa to 726.9 MPa. In contrast, the fiber membrane dressings prepared in Comparative Examples 2-3 have relatively poor mechanical properties, with Comparative Example 3 exhibiting the worst mechanical properties, with a longitudinal elastic modulus of only 516.2 MPa and a transverse elastic modulus of only 403.0 MPa. The data from Comparative Examples 1-3 show that grafting acrylic acid and carboxymethyl chitosan onto the surface of the fiber membrane can effectively improve the mechanical properties of the fiber membrane dressing. Furthermore, introducing pyridine groups into the functional monomers and compounding the functional monomers with acrylic acid and carboxymethyl chitosan, utilizing three-dimensional network structures and π-π stacking effects, can significantly improve the mechanical properties of the fiber membrane dressing. The swelling rate test results show that the maximum swelling rate of the fiber membrane dressings prepared in Examples 1-4 all reached over 893%. Among them, the maximum swelling rate of the fiber membrane dressing prepared in Example 2 was the highest, at 1077%. However, after swelling, its surface became rough and uneven, resulting in a poor skin feel. The maximum swelling rate of the fiber membrane dressing prepared in Example 1 was 924%, and the maximum swelling rate of the fiber membrane dressing prepared in Comparative Example 1 was 763%. The comparison shows that the quaternary ammonium salt groups introduced in the functional monomer can synergistically work with acrylic acid and carboxymethyl chitosan to significantly improve the swelling performance of the fiber membrane dressing, which is consistent with the water contact angle of the fiber membrane dressing surface. The antibacterial performance tests show that the fiber membrane dressings prepared in Examples 1-4 all exhibited antibacterial activity of over 99.6% against *Escherichia coli* and over 98.5% against *Staphylococcus aureus*. In contrast, the fiber membrane dressings prepared in Comparative Examples 1-3 showed antibacterial activities of 90.2%, 81.4%, and 66.3% against *Escherichia coli*, and 88.9%, 78.0%, and 64.1% against *Staphylococcus aureus*, respectively. These results indicate that the grafting of carboxymethyl chitosan and pyridine groups onto the surface of the fiber membrane can improve the antibacterial performance of the dressing to a certain extent. Furthermore, the quaternary ammonium salt groups, pyridine groups, and carboxymethyl chitosan synergistically enhance the antibacterial performance of the fiber membrane dressing. The drug loading rate test data shows that, compared to Comparative Example 3, the drug loading rate of the fiber membrane dressings prepared in Examples 1-4 was slightly lower, but still maintained a high level. The transdermal absorption test results showed that the permeation rate of the fiber membrane dressings prepared in Examples 1-4 and Comparative Example 1 was significantly higher than that in Comparative Examples 2-3. The data from Comparative Examples 1-3 showed that the introduction of pyridine groups and acrylate groups in the functional monomers could work together with carboxymethyl chitosan to significantly enhance the transdermal absorption capacity of the fiber membrane dressing by utilizing skin affinity and permeation-enhancing properties.

[0070] Although embodiments of this application have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of this application, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing an irradiated grafted modified fiber membrane dressing, characterized in that, Includes the following steps: Step S1: Mix 3-chloro-2-hydroxypropyl methacrylate, N,N-dimethylformamide and p-toluenesulfonic acid evenly, raise the temperature to 55-65℃ under stirring, add 4-pyridineacetic acid, react for 6-10h, cool to room temperature, extract the organic phase, remove the extraction solvent and dry. Step S2: Under a nitrogen atmosphere and stirring conditions, the product obtained in step S1 is dispersed in anhydrous ethanol, the temperature is raised to 70-80℃, potassium iodide and triethylamine are added, the reaction is carried out for 15-20 hours, and after cooling to room temperature, it is purified to obtain the functional monomer. Step S3: At room temperature, mix carboxymethyl chitosan and deionized water evenly and stir for 40-60 minutes. Then add acrylic acid, functional monomers and crosslinking agents in sequence and continue stirring for 10-30 minutes to obtain a mixed solution. Immerse the pretreated fiber membrane material in the mixed solution and then irradiate it to obtain the final product. In step S3, the mass ratio of acrylic acid, functional monomer, and carboxymethyl chitosan is 25:8-12:0.5-1.5, and the volume fraction of acrylic acid in the mixed solution is 5-10%. In step S3, the crosslinking agent is N,N'-methylenebisacrylamide, and the mass percentage of the crosslinking agent in the mixed solution is 0.25-0.75%. The specific steps of the irradiation treatment in step S3 are as follows: under a nitrogen atmosphere, the irradiation energy is set to 160-200 keV, and the irradiation dose is 40-70 kGy.

2. The method for preparing the irradiated grafted modified fiber membrane dressing according to claim 1, characterized in that, The molar ratio of 3-chloro-2-hydroxypropyl methacrylate, p-toluenesulfonic acid, and 4-pyridineacetic acid in step S1 is 1.1:0.01-0.02:0.8-1.

0.

3. The method for preparing the irradiated grafted modified fiber membrane dressing according to claim 1, characterized in that, In step S2, the molar ratio of the product obtained in step S1, potassium iodide, and triethylamine is 0.9:0.22-0.28:1.2-1.

4.

4. The method for preparing the irradiated grafted modified fiber membrane dressing according to claim 1, characterized in that, In step S2, the amount of the product obtained in step S1 added to the anhydrous ethanol is 0.2-0.4 g / mL.

5. The method for preparing the irradiated grafted modified fiber membrane dressing according to claim 1, characterized in that, The pretreatment process of the fiber membrane material in step S3 is as follows: ultrasonic cleaning is performed sequentially with anhydrous ethanol and water, followed by drying, to obtain the final product.

6. The irradiated grafted modified fiber membrane dressing prepared by any one of the methods described in claims 1-5.

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