Preparation method of novel anti-freezing, rewarming and antibacterial medical gel dressing

Abstract

The invention relates to a preparation method of a novel anti-freezing rewarming antibacterial medical gel dressing, belongs to the field of composite material-based hydrogel, and is applied to prevention and treatment of frostbite of field operating personnel in high-cold regions. The preparation method comprises the following step: reacting anhydrous copper chloride, polyvinylpyrrolidone and thiourea to obtain copper sulfide. The preparation method comprises the following steps: dispersing copper sulfide, polymerizing dopamine hydrochloride in an alkaline oxygen-containing environment to gather on the surface of the copper sulfide so as to form polydopamine copper sulfide (PDA-coated CuS), adding N 'N-methylene bisacrylamide and ammonium persulfate, stirring, pouring into a mold, and polymerizing in an environment of 60 DEG C, thereby obtaining PDA-coated CuS / Pro / PAM gel. CuS and PDA are combined, so that the biocompatibility and antibacterial property of CuS are enhanced, the photo-thermal property of dopamine is improved, and proline is used as an antifreeze agent to destroy hydrogen bonds of water molecules and inhibit formation of ice crystals. The medical gel dressing has the beneficial effects that the medical gel dressing with the anti-freezing, rewarming and antibacterial functions can be used in a low-temperature environment of-24 DEG C, and a good rewarming environment is provided for a frostbite part.

Description

Technical Field

[0001] The invention relates to a preparation method of a gel dressing, in particular to a preparation method of a novel antifreeze, rewarming and antibacterial medical gel dressing, belonging to the technical field of preparation of medical dressings. Background Art

[0002] When the human body is exposed to low temperatures in high-altitude cold areas, its body temperature is prone to drop, and organs such as the heart, brain, kidneys, and blood vessels will be damaged. If the body temperature drops below 28°C and cannot be rewarmed in time, it can directly cause death. Therefore, rapid rewarming is required after frostbite to prevent further cold exposure and restore blood circulation. Hydrogels have become ideal medical dressings due to their good biocompatibility and scalable functionality, but traditional hydrogels are difficult to inhibit ice crystal formation below 0°C and usually freeze and harden, thus losing their toughness, which seriously limits their scope of use. It is very important to prepare hydrogel dressings that can be used in low-temperature environments, and they show considerable potential in biomedical applications.

[0003] Copper sulfide (CuS) has been shown to be one of the most promising photothermal conversion materials, exhibiting photostability, photothermal antibacterial properties, and photothermal conversion capabilities. Polydopamine nanoparticles (PDA), which also exhibit excellent photothermal properties, biocompatibility, and biodegradability, are ideal candidates for CuS coatings in biomedical applications. The imine group in the zwitterion proline (L-pro) forms electrostatic interactions and hydrogen bonds with water molecules, generating hydration. This fundamentally disrupts the existing hydrogen bonding between water molecules and effectively prevents ice crystal formation. Therefore, the incorporation of proline can impart antifreeze properties to gel dressings.

[0004] Chinese patent publication number CN 109260509A, publication date 2019.01.25, invention name "A self-assembled contact antibacterial hydrogel excipient based on polydopamine and chitosan oligosaccharide and its preparation method", Chinese patent publication number CN110075346A, publication date 2019.08.02, invention name "A high-viscosity gel dressing and its preparation prevention", Chinese patent publication number CN 110947027A, publication date 2021.05.04, invention name "A self-healing hydrogel that inhibits bacteria and promotes wound repair", Chinese patent publication number CN 111228564A, publication date 2020.06.05, invention name "A new medical antibacterial and healing-promoting hydrogel dressing preparation method and its application", Chinese patent publication number CN Patent No. 111388748A, published on July 10, 2020, is titled "An antibacterial and hemostatic multifunctional composite hydrogel dressing and its preparation method." Patent No. CN216365553U, published on April 26, 2022, is titled "A nanohydrogel dressing with antibacterial and hemostatic function." Patent No. CN114748684A, published on July 15, 2022, is titled "An antibacterial hydrogel wound dressing that effectively promotes wound healing and its preparation method." Patent No. CN114949338A, published on August 30, 2022, is titled "A hydrogel with long-lasting resistance to drug-resistant bacteria, its preparation method, and application." These patents, through structural design, material composition, and preparation method selection, impart antibacterial, healing-promoting, high physical and mechanical strength, and good biocompatibility properties to the hydrogel. However, how to give the gel dressing antifreeze, rewarming and antibacterial properties so that the gel dressing can still effectively promote wound healing at lower temperatures has not been mentioned. Summary of the Invention

[0005] In view of the above problems, the present invention aims to provide a method for preparing a medical gel dressing that has antifreeze, rewarming and antibacterial functions and can effectively promote wound healing in a low temperature environment.

[0006] To achieve the above purpose, the technical solution is as follows:

[0007] 1. A method for preparing a novel antifreeze, rewarming, and antibacterial medical gel dressing, characterized in that the preparation method is carried out according to the following steps:

[0008] a. Preparation of PDA@CuS particles

[0009] Dissolve 0.0025-0.010 mol of anhydrous copper chloride and 0.25-0.10 g of polyvinyl pyrrolidone in 20-30 mL of DMF / water (1:1) and stir until uniformly. This is referred to as Solution A. Dissolve 0.0075-0.0175 mol of thiourea in 20-30 mL of DMF / water (1:1) and stir until uniformly. This is referred to as Solution B. Pour Solution B into Solution A, stir, and then pour into the reactor liner. React at 150°C for 12 hours. Centrifuge with deionized water and ethanol to eliminate any remaining unreacted compounds. The resulting CuS particles are then dried in a vacuum oven at 60°C for 24 hours, ground, and stored in a desiccator. 0.0075-0.015 g of dopamine hydrochloride was dissolved in 2.50-10.0 mL of Tris-HCl solution with a pH of 8.5, and after stirring for 10 min, 0.00-0.05 g of the above-prepared CuS nanoparticles were added respectively, and stirred for 2 h to obtain a PDA@CuS suspension.

[0010] Copper sulfide (CuS) has been shown to be one of the most promising materials for photothermal conversion due to its low cost and high photostability. It has been widely explored in photothermal antibacterial and photothermal conversion applications. Polydopamine nanoparticles have excellent photothermal properties, biocompatibility, biodegradability, and easy surface functionalization, making PDA an ideal choice for coating CuS for biomedical applications.

[0011] b. Preparation of PDA@CuS / Pro / PAM hydrogel

[0012] PDA@CuS / Pro / PAM hydrogel was prepared by a one-pot method. 1.25-2.0 g acrylamide was dissolved in the PDA@CuS suspension prepared above, and then different proportions of proline (0-30 wt%) were added and stirred for 30 min. Next, 0.0075-0.015 g N'N-methylenebisacrylamide (BIS) and 0.075-0.15 g ammonium persulfate (APS) were added and stirred. The prepared pregel was slowly and evenly poured into a mold and placed in an environment of 60 ° C for in situ free radical polymerization to obtain PDA@CuS / Pro / PAM hydrogel.

[0013] The high mechanical strength of the hydrogel can prevent the gel dressing from being damaged by external forces. The present invention introduces acrylamide (AM) into the PDA@CuS suspension, and forms a polyacrylamide chemical cross-linking network through temperature-induced polymerization, thereby enhancing the physical and mechanical properties of the gel dressing.

[0014] Water is a commonly used solvent for hydrogels, and its inherent melting point is 0°C. Water in hydrogels can exist in one of three different states: "free water", "weakly bound water" (often called "intermediate water"), and "unfrozen water", which have unique fluidity and different freezing temperatures. Free water has almost no interaction with the polymer network and is equivalent to water flowing freely outside, which will crystallize at around 0°C. Weakly bound water has little interaction with hydrophilic groups and will freeze at slightly below 0°C. Some water molecules have strong interactions with the gel network, the so-called "strongly bound water" or "unfrozen water", which maintains their fluidity and can remain liquid below -100°C. By increasing the interaction between water molecules and the polymer network, the amount of free water is reduced, the freezing temperature of the gel is lowered, or by forming hydrogen bonds with water molecules, reducing the hydrogen bonding force between water molecules, disrupting the formation of ice crystals, and giving the gel antifreeze ability.

[0015] Polymeric antimicrobial agents, such as quaternary ammonium salts and pyridinium salts, offer advantages such as high sterilization efficiency and long-lasting sterilization. However, they commonly suffer from poor thermal stability and processability. The present invention utilizes CuS as an antimicrobial agent, which exhibits high thermal stability. Polydopamine nanoparticles (PDA) are used as a coating for CuS biomedical applications, improving its biocompatibility.

[0016] The present invention uses zwitterionic proline (Pro) as an additive for the hydrogel dressing. The imine group in L-pro can form electrostatic interactions and hydrogen bonds with water molecules, generating hydration, fundamentally destroying the original hydrogen bond structure between water molecules and effectively preventing the formation of ice crystals in the system.

[0017] 2. The method for preparing a novel antifreeze, rewarming, and antibacterial medical gel dressing according to claim 1, wherein the photothermal conversion material and antibacterial agent used are copper sulfide (CuS) and polydopamine (PDA).

[0018] 3. The method for preparing a novel antifreeze, rewarming, and antibacterial medical gel dressing according to claim 1, wherein the additive used to enhance the physical and mechanical strength of the hydrogel is acrylamide (AM).

[0019] 4. The method for preparing a novel antifreeze, rewarming, and antibacterial medical gel dressing according to claim 1, wherein the additive used to enhance the antifreeze performance of the hydrogel is proline (Pro).

[0020] The gel dressing for preventing and treating frostbite for field workers in high-altitude cold regions and its preparation method provided by the present invention have the following advantages over the prior art:

[0021] 1) A one-pot method was used to prepare PDA@CuS / Pro / PAM gel wound dressing, which achieved simple preparation, simple equipment, and low cost;

[0022] 2) Using polydopamine (PDA) as a coating for copper sulfide (CuS) for biomedical applications, the PDA@CuS exhibits excellent photothermal performance and biocompatibility;

[0023] 3) The prepared gel dressing is compounded with four components, which respectively enhance mechanical properties (PAM), antifreeze (Pro), antibacterial properties (CuS), and photothermal conversion (PDA, CuS). After compounding, not only the mechanical properties are further enhanced, but also the antifreeze, rewarming, antibacterial properties and photothermal conversion are also improved.

[0024] 4) The gel dressing has good biocompatibility. The cell survival rate after culture with the gel extract can reach more than 90%, and the antibacterial rate against Escherichia coli and Staphylococcus aureus can be close to 100%. More importantly, it can inhibit the crystallization of water molecules at -24°C, maintain good viscoelasticity, and has antifreeze and water-retaining properties. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Figure 1 shows the antifreeze performance of PDA@CuS / Pro / PAM hydrogels. (a) shows a macroscopic image of the PDA / PAM hydrogel stretched at 25°C and -24°C; (b) shows a macroscopic image of the PDA@CuS / Pro30wt% / PAM hydrogel stretched at 25°C and -24°C.

[0026] Figure 2 The antibacterial performance of PDA@CuS / Pro / PAM gel is shown in Figure 1. (a) shows the plate test results of different samples treated with E. coli and Staphylococcus aureus; (b) shows the bacterial survival rate of E. coli after gel treatment; (c) shows the bacterial survival rate of Staphylococcus aureus after gel treatment.

[0027] Figure 3 Figure 1 shows the rewarming performance of PDA@CuS / Pro / PAM gels. (a) shows the temperature versus irradiation time (Tt) for different gel samples under a xenon lamp power density of 1 kW / m²; (b) shows the temperature difference versus irradiation time (ΔTt) for different gel samples under a xenon lamp power density of 1 kW / m². DETAILED DESCRIPTION

[0028] The present invention is described in detail below with reference to specific embodiments.

[0029] Example 1

[0030] A preparation method of a novel antifreeze, rewarming, and antibacterial medical gel dressing is as follows:

[0031] a. Preparation of PDA@CuS particles

[0032] 0.0025 mol of anhydrous copper chloride and 0.25 g of polyvinylpyrrolidone were dissolved in 20 mL of a 1:1 solution of DMF / water and stirred uniformly, designated Solution A. 0.0075 mol of thiourea was dissolved in 20 mL of a 1:1 solution of DMF / water and stirred uniformly, designated Solution B. Solution B was poured into Solution A, stirred, and then poured into the reactor liner. The reaction was carried out at 150°C for 12 hours. The mixture was then centrifuged with deionized water and ethanol to eliminate any remaining unreacted compounds. The resulting CuS particles were then dried in a vacuum oven at 60°C for 24 hours, ground, and stored in a desiccator. 0.0075 g of dopamine hydrochloride was dissolved in 2.5 mL of a pH 8.5 Tris-HCl solution and stirred for 10 minutes. Afterwards, 0.00 g of the CuS nanoparticles prepared above were added and stirred for 2 hours to obtain a PDA@CuS0.00 suspension.

[0033] b. Preparation of PDA@CuS / Pro / PAM hydrogel

[0034] PDA@CuS / Pro / PAM hydrogel was prepared by a one-pot method. 1.25 g acrylamide was dissolved in the PDA@CuS suspension prepared above, and then proline (0 wt%) in different proportions was added and stirred for 30 min. Next, 0.0075 g N'N-methylenebisacrylamide (BIS) and 0.075 g ammonium persulfate (APS) were added and stirred. The prepared pregel was slowly and evenly poured into a mold and placed in an environment of 60 ° C for in situ free radical polymerization to obtain PDA@CuS / Pro / PAM hydrogel.

[0035] Example 2

[0036] A preparation method of a novel antifreeze, rewarming, and antibacterial medical gel dressing is as follows:

[0037] a. Preparation of PDA@CuS particles

[0038] 0.0025 mol of anhydrous copper chloride and 0.50 g of polyvinylpyrrolidone were dissolved in 20 mL of a 1:1 solution of DMF / water and stirred uniformly, designated Solution A. 0.0120 mol of thiourea was dissolved in 20 mL of a 1:1 solution of DMF / water and stirred uniformly, designated Solution B. Solution B was poured into Solution A, stirred, and then poured into the reactor liner. The reaction was carried out at 150°C for 12 hours. The mixture was then centrifuged with deionized water and ethanol to eliminate any remaining unreacted compounds. The resulting CuS particles were then dried in a vacuum oven at 60°C for 24 hours, ground, and stored in a desiccator. 0.01 g of dopamine hydrochloride was dissolved in 5 mL of a pH 8.5 Tris-HCl solution and stirred for 10 minutes. Afterwards, 0.01 g of the CuS nanoparticles prepared above was added and stirred for 2 hours to obtain a PDA@CuS0.01 suspension.

[0039] b. Preparation of PDA@CuS / Pro / PAM hydrogel

[0040] PDA@CuS / Pro / PAM hydrogel was prepared by a one-pot method. 1.25 g acrylamide was dissolved in the PDA@CuS suspension prepared above, and then different proportions of proline (10 wt%) were added and stirred for 30 min. Next, 0.0075 g N'N-methylenebisacrylamide (BIS) and 0.075 g ammonium persulfate (APS) were added and stirred. The prepared pregel was slowly and evenly poured into a mold and placed in an environment of 60 ° C for in situ free radical polymerization to obtain PDA@CuS / Pro / PAM hydrogel.

[0041] Example 3

[0042] A preparation method of a novel antifreeze, rewarming, and antibacterial medical gel dressing is as follows:

[0043] a. Preparation of PDA@CuS particles

[0044] 0.0075 mol of anhydrous copper chloride and 0.75 g of polyvinylpyrrolidone were dissolved in 30 mL of DMF / water (1:1) and stirred until homogeneous, designated Solution A. 0.015 mol of thiourea was dissolved in 30 mL of DMF / water (1:1) and stirred until homogeneous, designated Solution B. Solution B was poured into Solution A, stirred, and then poured into the reactor liner. The reaction was carried out at 150°C for 12 hours. The mixture was then centrifuged with deionized water and ethanol to eliminate any remaining unreacted compounds. The resulting CuS particles were then dried in a vacuum oven at 60°C for 24 hours, ground, and stored in a desiccator. 0.0125 g of dopamine hydrochloride was dissolved in 7.5 mL of Tris-HCl (pH 8.5) and stirred for 10 minutes. Afterwards, 0.03 g of the CuS nanoparticles prepared above were added and stirred for 2 hours to obtain a PDA@CuS0.03 suspension.

[0045] b. Preparation of PDA@CuS / Pro / PAM hydrogel

[0046] PDA@CuS / Pro / PAM hydrogel was prepared by a one-pot method. 1.5 g acrylamide was dissolved in the PDA@CuS suspension prepared above, and then proline (20 wt%) in different proportions was added and stirred for 30 min. Next, 0.01 g N'N-methylenebisacrylamide (BIS) and 0.125 g ammonium persulfate (APS) were added and stirred. The prepared pregel was slowly and evenly poured into a mold and placed in an environment of 55-65 ° C for in situ free radical polymerization to obtain PDA@CuS / Pro / PAM hydrogel.

[0047] Example 4

[0048] A preparation method of a novel antifreeze, rewarming, and antibacterial medical gel dressing is as follows:

[0049] a. Preparation of PDA@CuS particles

[0050] 0.01 mol of anhydrous copper chloride and 1.0 g of polyvinylpyrrolidone were dissolved in 30 mL of a 1:1 solution of DMF / water and stirred uniformly, designated Solution A. 0.0175 mol of thiourea was dissolved in 30 mL of a 1:1 solution of DMF / water and stirred uniformly, designated Solution B. Solution B was poured into Solution A, stirred, and then poured into the reactor liner. The reaction was carried out at 150°C for 12 hours. The mixture was then centrifuged with deionized water and ethanol to eliminate any remaining unreacted compounds. The resulting CuS particles were then dried in a vacuum oven at 60°C for 24 hours, ground, and stored in a desiccator. 0.015 g of dopamine hydrochloride was dissolved in 10 mL of a pH 8.5 Tris-HCl solution and stirred for 10 minutes. Afterwards, 0.05 g of the previously prepared CuS nanoparticles were added and stirred for 2 hours to obtain a PDA@CuS0.05 suspension.

[0051] b. Preparation of PDA@CuS / Pro / PAM hydrogel

[0052] PDA@CuS / Pro / PAM hydrogel was prepared by a one-pot method. 1.5 g acrylamide was dissolved in the PDA@CuS suspension prepared above, and then different proportions of proline (30 wt%) were added and stirred for 30 min. Next, 0.01 g N'N-methylenebisacrylamide (BIS) and 0.15 g ammonium persulfate (APS) were added and stirred. The prepared pregel was slowly and evenly poured into a mold and placed in an environment of 60 ° C for in situ free radical polymerization to obtain PDA@CuS / Pro / PAM hydrogel.

[0053] Example 5

[0054] A preparation method of a novel antifreeze, rewarming, and antibacterial medical gel dressing is as follows:

[0055] a. Preparation of PDA@CuS particles

[0056] 0.01 mol of anhydrous copper chloride and 1.0 g of polyvinylpyrrolidone were dissolved in 30 mL of a 1:1 solution of DMF / water and stirred uniformly, designated Solution A. 0.0175 mol of thiourea was dissolved in 30 mL of a 1:1 solution of DMF / water and stirred uniformly, designated Solution B. Solution B was poured into Solution A, stirred, and then poured into the reactor liner. The reaction was carried out at 150°C for 12 hours. The mixture was then centrifuged with deionized water and ethanol to eliminate any remaining unreacted compounds. The resulting CuS particles were then dried in a vacuum oven at 60°C for 24 hours, ground, and stored in a desiccator. 0.015 g of dopamine hydrochloride was dissolved in 10 mL of a pH 8.5 Tris-HCl solution and stirred for 10 minutes. Afterwards, 0.05 g of the previously prepared CuS nanoparticles were added and stirred for 2 hours to obtain a PDA@CuS0.05 suspension.

[0057] b. Preparation of PDA@CuS / Pro / PAM hydrogel

[0058] PDA@CuS / Pro / PAM hydrogel was prepared by a one-pot method. 2.0 g acrylamide was dissolved in the PDA@CuS suspension prepared above, and then proline (30 wt%) in different proportions was added and stirred for 30 min. Next, 0.015 g N'N-methylenebisacrylamide (BIS) and 0.15 g ammonium persulfate (APS) were added and stirred. The prepared pregel was slowly and evenly poured into a mold and placed in an environment of 60 ° C for in situ free radical polymerization to obtain PDA@CuS / Pro / PAM hydrogel.

[0059] The medical gel dressing obtained by the method of the present invention has excellent antifreeze performance, antibacterial activity, and rewarming characteristics, has good biocompatibility, can promote wound healing in low-temperature environments, and can be used to prevent and treat frostbite for field workers in high-altitude cold areas.

[0060] What is disclosed above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto.

Claims

1. A method for preparing a novel antifreeze, rewarming and antibacterial medical gel dressing, characterized in that: It is prepared from the following raw materials: anhydrous copper chloride (CuCl2), polyvinyl pyrrolidone (PVP), thiourea (THU), polydopamine (PDA), proline (Pro), acrylamide (AM), N'N-methylenebisacrylamide (BIS), and ammonium persulfate (APS).

2. The method for preparing a novel antifreeze, rewarming and antibacterial medical gel dressing according to claim 1, characterized in that: The steps include: a. Preparation of PDA@CuS particles Dissolve 0.0025-0.010 mol of anhydrous copper chloride and 0.25-0.10 g of polyvinylpyrrolidone in 20-30 mL of a 1:1 DMF / water solution and stir until homogeneous. This is referred to as Solution A. Dissolve 0.0075-0.0175 mol of thiourea in 20-30 mL of a 1:1 DMF / water solution and stir until homogeneous. This is referred to as Solution B. Pour Solution B into Solution A, stir, and then pour into the reactor liner. React at 150°C for 12 hours. Centrifuge with deionized water and ethanol to eliminate any remaining unreacted compounds. The resulting CuS particles are then dried in a vacuum oven at 60°C for 24 hours, ground, and stored in a desiccator. 0.0075-0.015 g of dopamine hydrochloride was dissolved in 2.50-10.0 mL of Tris-HCl solution with a pH of 8.5, and after stirring for 10 min, 0.00-0.05 g of the above-prepared CuS nanoparticles were added respectively, and stirred for 2 h to obtain a PDA@CuS suspension. b. Preparation of PDA@CuS / Pro / PAM hydrogel PDA@CuS / Pro / PAM hydrogel was prepared by a one-pot method. 1.25-2.0 g acrylamide was dissolved in the PDA@CuS suspension prepared above, and then different proportions of proline (0-30 wt%) were added and stirred for 30 min. Next, 0.0075-0.015 g N'N-methylenebisacrylamide (BIS) and 0.075-0.15 g ammonium persulfate (APS) were added and stirred. The prepared pregel was slowly and evenly poured into a mold and placed in an environment of 60 ° C for in situ free radical polymerization to obtain PDA@CuS / Pro / PAM hydrogel.

3. The method for preparing a novel antifreeze, rewarming and antibacterial medical gel dressing according to claim 1, characterized in that: The rewarming materials and antibacterial agents used were copper sulfide (CuS) and polydopamine (PDA).

4. The method for preparing a novel antifreeze, rewarming and antibacterial medical gel dressing according to claim 1, characterized in that: The additive used to enhance the physical and mechanical strength of the hydrogel is acrylamide (AM).

5. The method for preparing a novel antifreeze, rewarming and antibacterial medical gel dressing according to claim 1, characterized in that: The additive used to enhance the antifreeze performance of the hydrogel is proline (Pro).

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