Alginate dressing and preparation method thereof

Abstract

The invention relates to the technical field of medical dressings, and particularly provides an alginate dressing and a preparation method thereof. The alginate dressing is prepared from the following components in percentage by mass: 50 to 70 percent of alginate, 10 to 30 percent of temperature-responsive polymer, 0.1 to 5 percent of antibacterial agent, 1 to 5 percent of ionic cross-linking agent, 0.5 to 2 percent of chemical cross-linking agent and the balance of deionized water and inevitable impurities, wherein the alginate dressing has a double cross-linked network, and the double cross-linked network is formed by forming an ionic bond with alginate through an ionic cross-linking agent and forming a covalent bond with a temperature-responsive polymer through a chemical cross-linking agent. According to the alginate dressing provided by the invention, the mechanical strength and the dynamic response performance of the dressing are improved by constructing a dual cross-linked network with a synergistic effect of ionic cross-linking and chemical cross-linking, and the dressing is endowed with rapid gelling capacity and high liquid absorbency by ionic cross-linking; the chemical crosslinking enhances the structural stability of the dressing in a body temperature environment, and avoids the defect that the traditional single crosslinking dressing is easy to disintegrate.

Description

Technical Field

[0001] The present invention relates to the technical field of medical dressings. Specifically, the present invention relates to an alginate dressing and a preparation method thereof. Background Art

[0002] As an important biomedical material, alginate dressings are widely used in the fields of wound repair and wound care due to their good biocompatibility, water absorption and adjustability.

[0003] However, traditional alginate dressings are relatively weak in physical properties, especially in terms of strength, flexibility and tear resistance. This makes them prone to rupture under long-term use or stress conditions, affecting their actual application effects. Secondly, since the cross-linking method of alginate dressings mainly relies on ionic cross-linking, their physical properties are not stable enough in an environment with temperature changes or humidity fluctuations, and they cannot effectively adapt to the changes in the wound environment.

[0004] Therefore, there is an urgent need for an alginate dressing that can improve physical properties to ensure that it is not easily ruptured under long-term use or external force. Summary of the Invention

[0005] The present invention provides an alginate dressing and a preparation method thereof. By constructing a dual cross-linking network with the synergistic effect of ionic cross-linking and chemical cross-linking, the mechanical strength and dynamic response performance of the dressing are significantly improved. Ionic cross-linking endows the dressing with rapid gel-forming ability and high liquid absorption; chemical cross-linking enhances the structural stability of the dressing in the body temperature environment, avoiding the defect of easy disintegration of traditional single-cross-linked dressings; the introduction of temperature-responsive polymers enables the dressing to adaptively adjust the porosity according to the temperature change of the wound surface, promoting oxygen penetration and cell migration, and accelerating wound healing; the synergistic effect of the antibacterial agent and the dual network achieves a long-term antibacterial effect, ensuring biological safety; the dressing has high liquid absorption, mechanical adaptability, antibacterial activity and low cytotoxicity, and can meet the clinical needs of complex wound repair.

[0006] The present invention provides an alginate dressing. The alginate dressing comprises the following components by mass percentage: alginate: 50 - 70%, temperature-responsive polymer: 10 - 30%, antibacterial agent: 0.1 - 5%, ionic crosslinking agent: 1 - 5%, chemical crosslinking agent: 0.5 - 2%, and the balance is deionized water and inevitable impurities. Among them, the alginate dressing has a double crosslinked network. The ionic crosslinking agent and alginate form the first network through ionic bonds, and the chemical crosslinking agent and the temperature-responsive polymer form the second network through covalent bonds. The first network and the second network together constitute the double crosslinked network. The ionic crosslinking agent includes a calcium chloride solution with a mass concentration of 5 - 10 wt%. The chemical crosslinking agent includes a glutaraldehyde solution with a mass concentration of 0.5 - 2 wt%. The alginate includes sodium alginate. The temperature-responsive polymer includes Pluronic F127 or a polyethylene glycol - polypropylene glycol triblock copolymer.

[0007] In any of the above technical solutions, the porosity of the alginate dressing is 80 - 95%, and the pore size is 50 - 200 μm.

[0008] In any of the above technical solutions, the antibacterial agent includes nano silver or chitosan.

[0009] In any of the above technical solutions, the mass concentration of the calcium chloride solution is 5 - 10 wt%; the mass concentration of the glutaraldehyde solution is 0.5 - 2 wt%.

[0010] In any of the above technical solutions, the residual amount of glutaraldehyde in the alginate dressing is ≤ 0.1 ppm, and the irradiation dose is 15 - 25 kGy.

[0011] The present invention also provides a preparation method of the alginate dressing. The preparation method of the alginate dressing is used to prepare the alginate dressing of any one of the above. The preparation method of the alginate dressing includes: S100. Dissolve the alginate in deionized water to obtain an alginate solution; dissolve the temperature-responsive polymer in deionized water to obtain a temperature-responsive polymer solution; add the temperature-responsive polymer solution to the alginate solution and perform a first stirring treatment to form a first mixed solution. S200. Disperse the antibacterial agent into the first mixed solution to obtain a second mixed solution. S300. Add the ionic crosslinking agent to the second mixed solution for an ionic crosslinking reaction, then add the chemical crosslinking agent for a chemical crosslinking reaction, and perform freeze-drying treatment to obtain the alginate dressing.

[0012] In any of the above technical solutions, in step S300: the temperature of the ionic crosslinking reaction is 20 - 30 °C, and the time is 1 - 2 h; and / or the temperature of the chemical crosslinking reaction is 40 - 50 °C, and the time is 2 - 4 h.

[0013] In any of the above technical solutions, the lyophilization treatment in step S300 includes: a first pre-freezing treatment and a second freezing treatment; the temperature of the first pre-freezing treatment is -50~-30°C, and the time is 10~14h; the temperature of the second freezing treatment is -30~-10°C, the vacuum degree is 5~50 Pa, and the time is 20~26h.

[0014] In any of the above technical solutions, in step S100, the concentration of the alginate solution is 3~8 wt%; the concentration of the temperature-responsive polymer solution is 5~15 wt%.

[0015] In any of the above technical solutions, after step S300, it further includes: S400, performing γ-ray sterilization treatment on the alginate dressing.

[0016] After adopting the technical solution of the present invention, the achievable technical effects are as follows: 1. Through the synergistic effect of ionic crosslinking and chemical crosslinking, an interpenetrating network structure is formed, significantly improving the tear strength and flexibility; the ionic crosslinking network enhances the water absorption and rapid gel-forming ability of the dressing; the chemical crosslinking network maintains the structural integrity at 37°C, avoiding the disintegration problem of traditional dressings caused by body temperature, enhancing the stability of the dressing, keeping the structure from disintegrating in the body temperature environment, and improving the tear resistance and flexibility. 2. Introducing a temperature-responsive polymer can adaptively adjust the porosity according to the change of wound surface temperature. At high temperature, the porosity of the dressing increases, promoting liquid absorption; at low temperature, the porosity decreases, maintaining structural stability, and the double crosslinking inhibits excessive swelling in a high-humidity environment, balancing the liquid absorption ability and structural stability, thereby helping to improve the wound healing environment and enhancing cell activity and tissue regeneration ability. 3. Nano-silver or chitosan as an antibacterial agent, in synergistic action with the double crosslinking network, ensures that the dressing can continuously release antibacterial substances when in long-term contact with the wound, reducing wound infection. Description of the Drawings

[0017] Figure 1 It is the drug release curve graph of Examples 1-3 and Comparative Examples 1-4 of the present invention. Detailed Embodiments

[0018] In order to more clearly understand the above-mentioned objects, features and advantages of the present invention, the present invention will be further described in detail below with reference to the drawings and specific embodiments. It should be noted that, without conflict, the embodiments of the present application and the features in the embodiments can be combined with each other.

[0019] In the following description, many specific details are set forth in order to provide a thorough understanding of the present invention. However, the present invention may be practiced in other ways than those specifically described herein, and thus, the scope of the present invention is not limited by the specific embodiments disclosed below.

[0020] To make the above objects, features, and advantages of the present aspect more apparent and understandable, the following provides a detailed description of specific embodiments of the present aspect.

[0021] As an important biomedical material, alginate dressings are widely used in the fields of wound repair and wound care due to their good biocompatibility, water absorbency, and tunability.

[0022] However, traditional alginate dressings still have defects. Firstly, their mechanical properties are insufficient. The three-dimensional network formed by single-ion crosslinking has low mechanical strength and is prone to breakage in dynamic wounds. Moreover, due to the lack of intelligent responsiveness, it often leads to the sudden release of antibacterial agents and cannot adapt to changes in the wound microenvironment.

[0023] Therefore, the present embodiment provides an alginate dressing and its preparation method. The alginate dressing has a double cross-linked network and temperature-responsive drug release, which solves the problems of poor mechanical properties and drug sudden release of traditional dressings. By constructing a double cross-linked network with the synergistic effect of ionic cross-linking and chemical cross-linking, the mechanical strength and dynamic response performance of the dressing are significantly improved. Ionic cross-linking endows the dressing with rapid gel-forming ability and high liquid absorbency; chemical cross-linking enhances the structural stability of the dressing in the body temperature environment and avoids the defect of easy disintegration of traditional single-cross-linked dressings; the introduction of temperature-responsive polymers enables the dressing to adaptively adjust the porosity according to the change of wound surface temperature, promotes oxygen penetration and cell migration, and accelerates wound healing; the synergistic effect of antibacterial agents and the double network achieves a long-term antibacterial effect and ensures biological safety.

[0024] The present embodiment provides a preparation method of an alginate dressing, including: S100: Dissolve alginate in deionized water to obtain an alginate solution; dissolve a temperature-responsive polymer in deionized water to obtain a temperature-responsive polymer solution; add the temperature-responsive polymer solution to the alginate solution and perform a first stirring treatment to form a first mixed solution; S200: Disperse an antibacterial agent into the first mixed solution to obtain a second mixed solution; S300: Add an ionic cross-linking agent to the second mixed solution for an ionic cross-linking reaction, then add a chemical cross-linking agent for a chemical cross-linking reaction, and perform freeze-drying treatment to obtain the alginate dressing.

[0025] Preferably, in step S100, dissolving alginate in deionized water can form a uniform alginate solution. As a natural polysaccharide, the solubility of alginate is closely related to the pH value and temperature of the solution. By using deionized water, interference from impurities can be avoided, ensuring the purity and stability of the solution. Dissolving the temperature-responsive polymer in deionized water forms a temperature-responsive polymer solution. The introduction of the temperature-responsive polymer enables the alginate dressing to respond to temperature changes at the wound site and adjust the physical properties of the dressing. For example, at low temperatures, the dressing may exhibit high water absorbency, while at high temperatures, it may show strong stability, which helps to meet the requirements of different wound environments. Dissolving alginate and the temperature-responsive polymer separately in deionized water can avoid phase separation problems caused by molecular chain entanglement or charge repulsion during direct mixing.

[0026] Furthermore, slowly adding the temperature-responsive polymer solution to the alginate solution and reducing the local concentration difference through gradient mixing to form a uniform first mixed solution. By uniformly mixing the two solutions, the distribution consistency of alginate and the temperature-responsive polymer is ensured. The linear chains of the two polymers physically interpenetrate in the solution, providing a pre-assembled structural basis for the subsequent cross-linking reaction, which is beneficial to forming a dressing with a stable double cross-linked network structure and enhancing the overall properties of the dressing, such as tensile strength and compressive resistance.

[0027] More preferably, the concentration of the alginate solution is 3 - 8 wt%, and the alginate includes sodium alginate. An appropriate concentration range can ensure that the alginate solution has appropriate viscosity and fluidity during preparation. Too low a concentration may result in an insufficiently viscous alginate solution, making it unable to effectively mix with the temperature-responsive polymer; while too high a concentration may lead to an overly viscous solution, affecting subsequent operations such as stirring and cross-linking reactions. The concentration of the temperature-responsive polymer solution is 5 - 15 wt%, and the temperature-responsive polymer includes Pluronic F127 or polyethylene glycol - polypropylene glycol triblock copolymer, which can ensure the effective concentration of the temperature-responsive polymer in the solution, enabling it to fully exhibit its temperature-responsive characteristics without being too concentrated to cause the solution to be overly viscous and affect subsequent stirring and cross-linking reactions. A moderate concentration helps to form a uniform solution, facilitating mixing with the alginate solution and thus enhancing the performance of the final dressing.

[0028] Preferably, in step S200, by uniformly dispersing the antibacterial agent into the first mixed solution, ensuring the uniform distribution of the antibacterial agent throughout the alginate dressing, which can effectively prevent infection at the wound site. Furthermore, the antibacterial agent includes silver nanoparticles and chitosan, which can inhibit the growth of various bacteria, fungi, and other microorganisms; silver nanoparticles can inhibit bacterial growth through multiple mechanisms due to their high specific surface area and interaction with the bacterial cell membrane; while chitosan exerts an antibacterial effect by binding to the bacterial cell wall.

[0029] Preferably, in step S300, the ionic cross-linking reaction is carried out by adding an ionic cross-linking agent to the second mixed solution, so that the carboxyl groups in the alginate molecules form ionic bonds with the metal ions in the cross-linking agent, thereby forming a network structure between the alginate molecules, improving the mechanical strength and stability of the dressing; and the ionic cross-linking structure helps to regulate the swelling property of the alginate dressing in water, ensuring that the dressing can maintain an appropriate moist environment at the wound site, avoiding excessive swelling or drying, thereby providing good wound care conditions. In addition, the cross-linked dressing has a certain stability in water, can continuously release the antibacterial agent, and provides a continuous antibacterial effect.

[0030] Further, the ionic cross-linking agent includes a calcium chloride solution with a concentration of 5-10 wt%. By selecting the calcium chloride solution as the ionic cross-linking agent, calcium ions (Ca 2+ ) form a stable ionic network with the negative charges (COO - ) in the alginate molecules, improving the mechanical strength and stability of the dressing, making it not easy to break or deform under external forces; the concentration range of the calcium chloride solution is selected to be 5-10 wt% to ensure that the concentration of calcium chloride can effectively cross-link the alginate without being too high to cause excessive viscosity of the solution or form an over-cross-linked network; the appropriate concentration ensures the efficient progress of the ionic cross-linking reaction and maintains the good fluidity and operability of the final product. The temperature of the ionic cross-linking reaction is 20-30 °C and the time is 1-2 h. The appropriate temperature range ensures the progress of the cross-linking reaction while avoiding damage to the polymer caused by high temperature. Excessive temperature may cause unnecessary gel transition of the temperature-responsive polymer, affecting the performance of the final dressing; the appropriate reaction time is sufficient for calcium ions to form stable ionic bonds with the negative charges in the alginate molecules, ensuring the formation of the cross-linked network without over-cross-linking. Too long cross-linking time may lead to too high cross-linking degree, affecting the operability and flexibility of the dressing.

[0031] Preferably, the chemical cross-linking reaction is carried out by adding a chemical cross-linking agent, so that the temperature-responsive polymer and the alginate molecules form a cross-linked network through covalent bonds, enhancing the characteristics of the temperature-responsive polymer, enabling the dressing to undergo physical property changes such as swelling or gelation according to temperature changes, thereby improving the adaptability of the dressing in different wound environments. In addition, it not only enhances the mechanical strength of the dressing, ensuring that the dressing will not break or be damaged due to external forces during wound treatment, but also improves the durability of the dressing, enabling it to withstand mechanical stress and environmental changes for a long time during use and reducing the need for repeated replacement.

[0032] Furthermore, the chemical crosslinking agent includes a 0.5 - 2 wt% glutaraldehyde solution. Glutaraldehyde reacts with the temperature-responsive polymer (such as Pluronic F127 or polyethylene glycol - polypropylene glycol triblock copolymer) through the reactive aldehyde group (-CHO) at the end and the hydroxyl group (-OH) or amino group (-NH 2 2 ) in alginate to form covalent bonds, thereby constructing a crosslinked network, significantly enhancing the mechanical properties of the dressing, making it have better durability and stability. And through chemical crosslinking, the structure of the dressing is more stable, not easily affected by the external environment, extending the service life of the dressing. In addition, moderate chemical crosslinking can adjust the physical properties of the dressing, such as hardness, elasticity, swelling, etc., ensuring that the dressing can maintain sufficient flexibility and certain firmness during use. Finally, through appropriate chemical crosslinking, it can ensure that the dressing has an ideal adaptability when contacting the wound, such as being able to maintain a certain shape and strength when needed and gradually providing support during the healing process. The concentration of the glutaraldehyde solution is set at 0.5 - 2 wt%, and this concentration range helps to ensure the moderate progress of the crosslinking reaction. Too high a concentration may lead to over-crosslinking, affecting the flexibility and operability of the dressing, while too low a concentration may lead to incomplete crosslinking reaction, affecting the strength and stability of the dressing. The temperature of the chemical crosslinking reaction is 40 - 50 °C, and the time is 2 - 4 h. The temperature and time of the chemical crosslinking reaction directly affect the crosslinking efficiency and degree between glutaraldehyde and alginate and the temperature-responsive polymer. The appropriate temperature ensures that glutaraldehyde can react fully with the polymer material, and at the same time, it will not cause the denaturation or degradation of the temperature-responsive polymer due to too high a temperature. Sufficient reaction time ensures the complete progress of the crosslinking reaction, while avoiding irreversible changes in the polymer structure caused by too long a reaction time; thus effectively controlling the degree of the crosslinking reaction, ensuring the formation of the crosslinked network structure, and at the same time maintaining the appropriate flexibility of the dressing. Too high a temperature and too long a time may make the dressing too hard or brittle, affecting its comfort and usability.

[0033] Preferably, the lyophilization treatment in step S300 includes: a first pre-freezing treatment and a second freezing treatment; the temperature of the first pre-freezing treatment is -50~-30°C, and the time is 10~14h; the temperature of the second freezing treatment is -30~-10°C, the vacuum degree is 5~50Pa, and the time is 20~26h. The purpose of the first pre-freezing treatment is to quickly cool the solution to -50~-30°C, so that the water in it freezes rapidly, thereby controlling the freezing rate, ensuring that the water precipitates in the form of ice crystals, and preventing the formation of too large or uneven ice crystal structures; and within this temperature range, the water can freeze quickly, which will result in smaller and more evenly distributed ice crystal particles. The process of rapid freezing of water helps to reduce the time of ice crystal growth, thereby controlling the size of the ice crystals. Smaller ice crystals can reduce the damage to the pore structure in the subsequent process, contribute to the formation of a more uniform and stable pore structure, and can reduce the pressure of ice crystal expansion on the material, preventing the structure of the dressing from collapsing or deforming due to uneven ice crystal growth. Pre-freezing for 10~14h is to ensure that the water can be completely frozen and a sufficient ice crystal distribution is achieved. Too short a time may lead to incomplete freezing, affecting the subsequent lyophilization effect; while too long a time may lead to instability of the polymer structure or over-freezing. Therefore, 10~14 hours is an optimized treatment duration.

[0034] For example, the purpose of the second freezing treatment stage is to remove water through the sublimation process. In this stage, the temperature is slightly raised to -30~-10°C and it is carried out in a vacuum environment. The water can directly change from a solid state to a gaseous state, avoiding the formation of liquid water, thereby minimizing structural damage. And this process can effectively remove water while ensuring the retention of pores; the vacuum degree provides a low-pressure environment for sublimation. The low pressure helps to improve the efficiency of water conversion into a gaseous state and avoid an overly long liquid phase state; secondly, the sublimation process retains the pore structure formed by ice crystals, avoiding the possible shrinkage of pores during the water evaporation process. The long-time treatment ensures that the water in the dressing is completely removed and no residual water is left due to short-time treatment, ensuring the stability and long-term storage of the dressing.

[0035] Furthermore, after completely removing the water, the dressing will maintain a high porosity and appropriate pore size. These pores contribute to the liquid absorption property of the dressing, enabling it to effectively absorb wound exudates, maintain a moist environment for the wound, and contribute to wound healing. The moderate pore size helps the growth of cells and the transport of nutrients, promoting wound healing. Preferably, the porosity of the final alginate dressing is 80~95%, and the pore size is 50~200μm. The appropriate porosity helps the dressing to provide better water absorption and breathability in actual use, and the appropriate pore size helps the adsorption of wound exudates and the maintenance of a moist environment, contributing to the promotion of wound healing.

[0036] Preferably, in step S400, the alginate dressing is sterilized by gamma rays, which can effectively kill microorganisms such as bacteria, viruses, and fungi that may exist on the surface and inside the alginate dressing. By irradiating with high-energy gamma rays, it can damage the DNA or RNA of microorganisms, causing them to be unable to reproduce or lose their activity, thus achieving the sterilization effect. Due to the strong penetration of gamma rays, it can penetrate deep into the dressing to ensure that even the deep parts can receive sufficient irradiation and ensure the overall sterilization of the product.

[0037] Example 1 This example provides an alginate dressing and its preparation method. The alginate dressing consists of the following components by mass percentage: Sodium alginate: 60%, Pluronic F127: 20%, nano silver: 2%, 8wt% calcium chloride solution: 2%, 1wt% glutaraldehyde solution: 1%, and the balance is deionized water and inevitable impurities; The preparation method includes: S100. Dissolve sodium alginate in deionized water to obtain a 5wt% sodium alginate solution; dissolve the temperature-responsive polymer in deionized water to obtain a 10wt% temperature-responsive polymer solution; add the temperature-responsive polymer solution to the sodium alginate solution and perform a first stirring treatment to form a first mixed solution; S200. Disperse the antibacterial agent into the first mixed solution to obtain a second mixed solution; S300. Add an ionic crosslinking agent to the second mixed solution, perform an ionic crosslinking reaction at a temperature of 25°C for 1 h, then add a chemical crosslinking agent, and perform a chemical crosslinking reaction at a temperature of 45°C for 3 h, and then perform freeze-drying treatment to obtain the alginate dressing; S400. Perform gamma-ray sterilization treatment on the alginate dressing; Among them, the freeze-drying treatment includes: a first pre-freezing treatment and a second freezing treatment; The temperature of the first pre-freezing treatment is -40°C and the time is 12 h; The temperature of the second freezing treatment is -20°C, the vacuum degree is 15 Pa, and the time is 24 h.

[0038] Example 2 This example provides an alginate dressing and its preparation method. The alginate dressing consists of the following components by mass percentage: Sodium alginate: 70%, polyethylene glycol - polypropylene glycol triblock copolymer: 10%, nano silver: 0.1%, 10wt% calcium chloride solution: 1%, 2wt% glutaraldehyde solution: 0.5%, and the balance is deionized water and inevitable impurities; The preparation method includes: S100. Dissolve alginate in deionized water to obtain an 8 wt% alginate solution; dissolve the polyethylene glycol - polypropylene glycol triblock copolymer in deionized water to obtain a 15 wt% polyethylene glycol - polypropylene glycol triblock copolymer solution; add the temperature - responsive polymer solution to the alginate solution and perform a first stirring treatment to form a first mixed solution; S200. Disperse the antibacterial agent into the first mixed solution to obtain a second mixed solution; S300. Add an ionic cross - linker to the second mixed solution, perform an ionic cross - linking reaction at a temperature of 30 °C for 1 h, then add a chemical cross - linker, and perform a chemical cross - linking reaction at a temperature of 50 °C for 2 h, and then perform freeze - drying treatment to obtain the alginate dressing; S400. Perform γ - ray sterilization treatment on the alginate dressing; Among them, the freeze - drying treatment includes: a first pre - freezing treatment and a second freezing treatment; The temperature of the first pre - freezing treatment is - 30 °C and the time is 10 h; The temperature of the second freezing treatment is - 10 °C, the vacuum degree is 10 Pa, and the time is 20 h.

[0039] Example 3 This example provides an alginate dressing and its preparation method. The alginate dressing comprises the following components by mass percentage: Sodium alginate: 50%, Pluronic F127: 30%, nano - silver: 5%, 5 wt% calcium chloride solution: 5%, 0.5 wt% glutaraldehyde solution: 2%, and the balance is deionized water and unavoidable impurities; The preparation method includes: S100. Dissolve alginate in deionized water to obtain a 3 wt% alginate solution; dissolve the temperature - responsive polymer in deionized water to obtain a 5 wt% temperature - responsive polymer solution; add the temperature - responsive polymer solution to the alginate solution and perform a first stirring treatment to form a first mixed solution; S200. Disperse chitosan into the first mixed solution to obtain a second mixed solution; S300. Add an ionic cross - linker to the second mixed solution, perform an ionic cross - linking reaction at a temperature of 20 °C for 2 h, then add a chemical cross - linker, and perform a chemical cross - linking reaction at a temperature of 40 °C for 4 h, and then perform freeze - drying treatment to obtain the alginate dressing; Among them, the freeze - drying treatment includes: a first pre - freezing treatment and a second freezing treatment; The temperature of the first pre - freezing treatment is - 50 °C and the time is 14 h; The temperature of the second freezing treatment is -30°C, the vacuum degree is 45 Pa, and the time is 26 h.

[0040] Comparative Example 1 This comparative example provides an alginate dressing and its preparation method. The alginate dressing comprises the following components by mass percentage: Sodium alginate: 60%, Pluronic F127: 20%, nano silver: 2%, 8 wt% calcium chloride solution: 2%, and the balance is deionized water and inevitable impurities; The preparation method is the same as that of Example 1, except that no chemical cross-linking agent is added in step S300.

[0041] Comparative Example 2 This comparative example provides an alginate dressing and its preparation method. The alginate dressing comprises the following components by mass percentage: Sodium alginate: 60%, Pluronic F127: 20%, nano silver: 2%, 1 wt% glutaraldehyde solution: 1%, and the balance is deionized water and inevitable impurities; The preparation method is the same as that of Example 1, except that no ionic cross-linking agent is added in step S300.

[0042] Comparative Example 3 This comparative example provides an alginate dressing and its preparation method. The alginate dressing comprises the following components by mass percentage: Sodium alginate: 60%, Pluronic F127: 20%, nano silver: 2%, and the balance is deionized water and inevitable impurities; The preparation method is the same as that of Example 1, except that no ionic cross-linking agent and chemical cross-linking agent are added in step S300.

[0043] Comparative Example 4 This comparative example provides an alginate dressing and its preparation method. The alginate dressing is obtained by purchasing.

[0044]

Experimental data

[0045] Liquid absorption rate test: Cut 2 cm × 2 cm square specimens (with an area of S) from the alginate dressings of Examples 1-3 and Comparative Examples 1-4, dry and weigh them to obtain the initial weight W. 0 Fully immerse the specimens in the solution, and record the liquid absorption amounts W at time t = 5, 10, and 30 min respectively. t And calculate the liquid absorption rate.

[0046] Glutaraldehyde residue detection: Cut 1 g of the alginate dressings of Examples 1-3 and Comparative Examples 1-4 into pieces, add 10 mL of acetonitrile-water (1:1) mixed solvent, ultrasonically extract for 30 min, centrifuge (10000 rpm, 10 min), take the supernatant and filter (0.22 μm membrane), and calculate the residue amount by external standard method through HPLC.

[0047] Bacteriostatic rate test: Inoculate Staphylococcus aureus and Escherichia coli strains into nutrient broth, culture at 37 °C for 18 h, adjust the concentration to 1×10 6 CFU / mL. Co-culture 1 cm dressings of Examples 1-3 and Comparative Examples 1-4 with 1 mL of the bacterial solution (37 °C, 24 h). Take 100 μL of the mixed solution, dilute it by gradient, spread it on an agar plate, culture at 37 °C for 24 h, count the surviving colonies (N t ), and calculate the bacteriostatic rate.

[0048] It can be seen from the above table that due to the double cross-linked network in Examples 1-3, the tensile strength is significantly higher than that of the comparative examples. Since there is no cross-linking reaction in Comparative Example 3, a solid structure cannot be formed; the liquid absorption rate of Examples 1-3 is 2-3 times that of Comparative Example 4; the residue amount in Examples 1-3 is controlled at ≤0.1 ppm through γ-ray sterilization, meeting the medical standards; the bacteriostatic rates of Examples 1-3 are much higher than those of Comparative Examples 1-4.

[0049] Drug release rate test: Cut the alginate dressings of Examples 1-3 and Comparative Examples 1-4 into 1 cm diameter discs, accurately weigh m, and immerse them in a small amount of phosphate buffer solution with pH 7.4 for 30 minutes to balance. Then put them into a dialysis bag, seal it, and immerse it in a conical flask containing phosphate buffer solution with pH 7.4. Keep it oscillating at a constant temperature of 37 ± 0.5 °C and a rotation speed of 50-100 rpm. Take 1-2 mL of the supernatant at 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h respectively, detect it by high performance liquid chromatography, and calculate the drug release rate. The results are shown in Table 2 and Figure 1 as shown.

[0050] Table 2 From Table 2 and Figure 1It can be obtained that in Examples 1-3, the drug release was slow within 1-6 h, less than 30%, reflecting the initial controlled release ability; after 12 h, the drug release rate increased significantly, reaching 45-50%, and at 24 h, it reached 70-77%, indicating that the temperature-responsive polymer undergoes a phase change at body temperature, triggering the accelerated release of the drug to meet the treatment needs for infections with a fever higher than 38 °C; while in Comparative Example 1, only ionic cross-linking was used. Due to the lack of a chemical cross-linking network, the burst release rate was as high as 20.3%, and the drug release rate at 24 h was 92.3%, indicating that single cross-linking cannot effectively control the release; in Comparative Example 2, only chemical cross-linking was used, and the initial burst release was 18.5%, lower than that in Comparative Example 1. However, due to the lack of rapid gelation of ionic cross-linking, the drug diffusion resistance was insufficient, and the drug release rate at 24 h was still as high as 85.6%; in Comparative Example 3, there was no cross-linking, and 35% of the drug was released within 1 h, reaching 98.5% at 24 h, confirming that the uncross-linked material cannot form an effective controlled release barrier; compared with the commercially available traditional alginate dressing, the drug release rate at 24 h reached 90.5%, and there was no temperature-responsive property, demonstrating the significant advantage of the present invention in intelligent controlled release.

[0051] Porosity and pore size: The alginate dressings of Examples 1-3 and Comparative Examples 1-4 were freeze-dried and cut into cylindrical samples with a diameter of 5-10 mm and a thickness of 2-3 mm, placed in a vacuum drying oven at 60 °C for 24 h to remove residual moisture, and the porosity and pore size were measured by mercury intrusion method. The results are shown in Table 3.

[0052] Table 3 The double cross-linking network in Examples 1-3 stabilized the ice crystal growth framework during freeze-drying, avoided drying collapse, and formed a high-porosity structure, while the high porosity directly increased the liquid absorption rate; in Comparative Example 1, only ionic cross-linking was used. Due to the lack of a chemical cross-linking network, part of the structure collapsed during freeze-drying, and the proportion of closed pores was high, resulting in a decrease in the liquid absorption rate; in Comparative Example 2, only chemical cross-linking was used, and excessive cross-linking with glutaraldehyde caused the polymer chains to be closely packed, forming a microporous structure that hindered the rapid penetration of liquid; in Comparative Example 3, there was no cross-linking, and the freeze-dried skeleton could not be maintained, and a porous structure could not be formed; in Comparative Example 4, the macroporous structure was prone to disintegration after absorbing liquid.

[0053] In the description of this specification, the descriptions of terms such as "one embodiment", "some embodiments", "specific embodiments", etc. mean 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 representations of the above terms do 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.

[0054] Although the present invention is disclosed as above, the present invention is not limited thereto. Any person skilled in the art can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the scope defined by the claims.

Claims

1. An alginate dressing, characterized in that: The alginate dressing comprises the following components in percentage by weight: Alginate: 50~70%, temperature responsive polymer: 10~30%, antibacterial agent: 0.1~5%, ionic crosslinking agent: 1~5%, chemical crosslinking agent: 0.5~2%, the balance is deionized water and unavoidable impurities; Wherein, the alginate dressing has a double cross-linked network, the ionic cross-linking agent and the alginate form a first network through ionic bonds, the chemical cross-linking agent and the temperature-responsive polymer form a second network through covalent bonds, and the first network and the second network together constitute the double cross-linked network; The ionic crosslinking agent includes a calcium chloride solution with a mass concentration of 5-10wt%; the chemical crosslinking agent includes a glutaraldehyde solution with a mass concentration of 0.5-2wt%; the alginate includes sodium alginate; and the temperature responsive polymer includes Pluronic F127 or a polyethylene glycol-polypropylene glycol triblock copolymer.

2. The alginate dressing according to claim 1, characterized in that The alginate dressing has a porosity of 80-95% and a pore size of 50-200 μm.

3. The alginate dressing according to claim 1, characterized in that The antibacterial agent includes nanosilver or chitosan.

4. The alginate dressing according to claim 1, characterized in that The residual glutaraldehyde in the alginate dressing is ≤0.1ppm, and the irradiation dose is 15-25kGy.

5. A method for preparing an alginate dressing, characterized in that: The method for preparing the alginate dressing is used to prepare the alginate dressing according to any one of claims 1 to 4, and the method for preparing the alginate dressing comprises: S100, dissolving the alginate in deionized water to obtain an alginate solution; dissolving the temperature responsive polymer in deionized water to obtain a temperature responsive polymer solution; adding the temperature responsive polymer solution to the alginate solution, performing a first stirring process, and forming a first mixed solution; S200, dispersing the antibacterial agent into the first mixed solution to obtain a second mixed solution; S300, adding the ionic crosslinking agent to the second mixed solution to carry out an ionic crosslinking reaction, then adding the chemical crosslinking agent to carry out a chemical crosslinking reaction, and performing freeze-drying treatment to obtain the alginate dressing.

6. The preparation method according to claim 5, characterized in that: In step S300: The temperature of the ionic crosslinking reaction is 20-30° C. and the time is 1-2 hours; and / or The temperature of the chemical cross-linking reaction is 40-50° C. and the time is 2-4 hours.

7. The preparation method according to claim 5, characterized in that: The freeze-drying process in step S300 includes: a first pre-freezing process and a second freezing process; The temperature of the first pre-freezing treatment is -50 to -30°C and the time is 10 to 14 hours; The temperature of the second freezing treatment is -30~-10°C, the vacuum degree is 5~50Pa, and the time is 20~26h.

8. The preparation method according to claim 5, characterized in that: In step S100, The concentration of the alginate solution is 3-8wt%; The concentration of the temperature responsive polymer solution is 5-15wt%.

9. The preparation method according to claim 5, characterized in that: After step S300, the method further includes: S400, performing gamma-ray sterilization on the alginate dressing.

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