Alginate dressing and preparation method thereof

Abstract

The present invention relates to the technical field of medical dressings, and specifically provides an alginate dressing and a preparation method thereof; the alginate dressing of the present invention comprises the following components in percentage by mass: 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; wherein, the alginate dressing has a double crosslinking network, the double crosslinking network is composed of ionic bonds formed between the ionic crosslinking agent and the alginate, and covalent bonds formed between the chemical crosslinking agent and the temperature-responsive polymer. The alginate dressing provided by the present invention improves the mechanical strength and dynamic response performance of the dressing by constructing a double crosslinking network with synergistic effects of ionic crosslinking and chemical crosslinking. Ionic crosslinking gives the dressing rapid gelling ability and high liquid absorption; chemical crosslinking enhances the structural stability of the dressing under body temperature environment, avoiding the defect of easy disintegration of traditional single crosslinking dressings.

Description

Technical Field

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

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

[0003] However, traditional alginate dressings are relatively weak in terms of physical properties, especially in terms of strength, flexibility, and tear resistance. This makes them prone to rupture after prolonged use or under stress, affecting their practical application. Secondly, because alginate dressings rely primarily on ionic crosslinking, their physical properties are not stable enough in environments with temperature or humidity fluctuations, making them unable to effectively adapt to 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 broken under long-term use or external force conditions. Summary of the Invention

[0005] The present invention provides an alginate dressing and a preparation method thereof. By constructing a double cross-linked network with synergistic effects of ionic cross-linking and chemical cross-linking, the mechanical strength and dynamic response performance of the dressing are significantly improved. Ionic cross-linking gives the dressing rapid gelling ability and high liquid absorption; chemical cross-linking enhances the structural stability of the dressing under 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 changes in wound temperature, promotes oxygen permeation and cell migration, and accelerates wound healing; the synergistic effect of the antibacterial agent and the double network achieves a long-lasting antibacterial effect, ensuring biosafety; 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 invention provides an alginate dressing, which comprises the following components in percentage by weight: 50-70% alginate, 10-30% temperature-responsive polymer, 0.1-5% antibacterial agent, 1-5% ionic crosslinking agent, 0.5-2% chemical crosslinking agent, and the balance being deionized water and inevitable impurities. The alginate dressing has a double crosslinked network, wherein the ionic crosslinking agent and alginate form a first network through ionic bonds, and the chemical crosslinking 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 crosslinked network. The ionic crosslinking agent comprises a calcium chloride solution with a mass concentration of 5-10wt%; the chemical crosslinking agent comprises a glutaraldehyde solution with a mass concentration of 0.5-2wt%; the alginate comprises sodium alginate; and the temperature-responsive polymer comprises 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 nanosilver or chitosan.

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

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

[0011] The present invention also provides a method for preparing an alginate dressing, which is used to prepare any of the above-mentioned alginate dressings. The method for preparing the alginate dressing includes: S100, dissolving alginate in deionized water to obtain an alginate solution; dissolving a 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 treatment, and forming a first mixed solution; S200, dispersing an antibacterial agent into the first mixed solution to obtain a second mixed solution; S300, adding an ionic crosslinking agent to the second mixed solution to perform an ionic crosslinking reaction, then adding a chemical crosslinking agent to perform a chemical crosslinking reaction, and performing a freeze-drying treatment to obtain an 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 hours; and / or the temperature of the chemical crosslinking reaction is 40-50° C., and the time is 2-4 hours.

[0013] In any of the above technical solutions, the freeze-drying 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℃, and the time is 10~14h; the temperature of the second freezing treatment is -30~-10℃, the vacuum degree is 5~50Pa, 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, the following further steps are included: S400, performing gamma-ray sterilization on the alginate dressing.

[0016] After adopting the technical solution of the present invention, the technical effects that can be achieved are as follows:

[0017] 1. Through the synergistic effect of ionic crosslinking and chemical crosslinking, an interpenetrating network structure is formed, significantly improving tear resistance and flexibility. The ionic crosslinking network enhances the water absorption and rapid gelation ability of the dressing. The chemical crosslinking network maintains structural integrity at 37°C, avoiding the disintegration problem of traditional dressings caused by body temperature. It enhances the stability of the dressing, allowing it to maintain structural disintegration at body temperature, and improves tear resistance and flexibility.

[0018] 2. The introduction of temperature-responsive polymers can adaptively adjust the porosity according to changes in wound temperature. At high temperatures, the porosity of the dressing increases, promoting fluid absorption; at low temperatures, the porosity decreases, maintaining structural stability. Furthermore, double cross-linking inhibits excessive swelling in high humidity environments, balancing fluid absorption capacity and structural stability, thereby helping to improve the wound healing environment, enhance cell activity, and increase tissue regeneration capacity.

[0019] 3. Nanosilver or chitosan acts as an antibacterial agent, synergistically with the double cross-linked network to ensure that the dressing can continuously release antibacterial substances when in contact with the wound for a long time, thereby reducing wound infection. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The drug release curves of Examples 1-3 and Comparative Examples 1-4 of the present invention are shown. DETAILED DESCRIPTION

[0021] In order to more clearly understand the above-mentioned objects, features and advantages of the present invention, the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments. It should be noted that, in the absence of conflict, the embodiments of the present application and the features therein can be combined with each other.

[0022] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Therefore, the scope of protection of the present invention is not limited to the specific embodiments disclosed below.

[0023] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below.

[0024] As an important biomedical material, alginate dressing is widely used in the fields of wound repair and wound care due to its good biocompatibility, water absorption and adjustability.

[0025] However, traditional alginate dressings still have defects. First, the mechanical properties are insufficient. The three-dimensional network formed by single ion cross-linking has low mechanical strength and is prone to breakage in dynamic wounds. In addition, due to the lack of intelligent responsiveness, it often leads to sudden release of antibacterial agents and cannot adapt to changes in the wound microenvironment.

[0026] Therefore, this embodiment provides an alginate dressing and a preparation method thereof, which has a double cross-linked network and temperature-responsive drug release, and solves the problems of poor mechanical properties and sudden drug release of traditional dressings. By constructing a double cross-linked network with synergistic effects of ionic cross-linking and chemical cross-linking, the mechanical strength and dynamic response performance of the dressing are significantly improved. Ionic cross-linking gives the dressing rapid gelation ability and high liquid absorption; chemical cross-linking enhances the structural stability of the dressing under 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 changes in wound temperature, promote oxygen permeation and cell migration, and accelerate wound healing; the synergistic effect of the antibacterial agent and the double network achieves a long-lasting antibacterial effect, ensuring biosafety.

[0027] This embodiment provides a method for preparing an alginate dressing, comprising:

[0028] S100, dissolving alginate in deionized water to obtain an alginate solution; dissolving a temperature-responsive polymer in deionized water to obtain a temperature-responsive polymer solution; adding the temperature-responsive polymer solution to the alginate solution and performing a first stirring process to form a first mixed solution;

[0029] S200, dispersing the antibacterial agent into the first mixed solution to obtain a second mixed solution;

[0030] S300, adding an ionic crosslinking agent to the second mixed solution to carry out an ionic crosslinking reaction, then adding a chemical crosslinking agent to carry out a chemical crosslinking reaction, and performing freeze-drying to obtain an alginate dressing.

[0031] Preferably, in step S100, alginate is dissolved in deionized water to 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, the interference of impurities can be avoided, ensuring the purity and stability of the solution. The temperature-responsive polymer is dissolved in deionized water to form 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 higher water absorption, while at high temperatures, it may exhibit stronger stability, which helps to meet the needs of different wound environments. The alginate and the temperature-responsive polymer are dissolved separately in deionized water to avoid phase separation problems caused by molecular chain entanglement or charge repulsion when directly mixed.

[0032] Furthermore, the temperature-responsive polymer solution is slowly added to the alginate solution, and the local concentration difference is reduced through gradient mixing to form a uniform first mixed solution. By uniformly mixing the two solutions, the distribution consistency of alginate and temperature-responsive polymer is ensured. The linear chains of the two polymers physically interpenetrate in the solution, providing a pre-assembled structural basis for subsequent cross-linking reactions, which is conducive to the formation of a dressing with a stable double cross-linked network structure and enhancing the overall performance of the dressing, such as tensile strength and compressive resistance.

[0033] Furthermore, the concentration of the alginate solution is 3-8wt%, and the alginate includes sodium alginate. This appropriate concentration range ensures that the alginate solution has appropriate viscosity and fluidity during the preparation process. A too low concentration may result in the alginate solution being insufficiently viscous and unable to effectively mix with the temperature-responsive polymer; while a too high concentration may cause the solution to be too viscous, affecting subsequent operations such as stirring and cross-linking reactions. The concentration of the temperature-responsive polymer solution is 5-15wt%, and the temperature-responsive polymer includes Pluronic F127 or a polyethylene glycol-polypropylene glycol triblock copolymer. This ensures an effective concentration of the temperature-responsive polymer in the solution, allowing it to fully utilize its temperature-responsive properties without causing the solution to become too viscous, which would affect subsequent stirring and cross-linking reactions. The appropriate concentration helps form a uniform solution, facilitating mixing with the alginate solution, thereby enhancing the performance of the final dressing.

[0034] Preferably, in step S200, by uniformly dispersing the antimicrobial agent into the first mixed solution, the uniform distribution of the antimicrobial agent in the entire alginate dressing is ensured, thereby effectively preventing infection at the wound site. Furthermore, the antimicrobial agent includes nanosilver and chitosan, which can inhibit a variety of microorganisms such as bacteria and fungi; nanosilver can inhibit bacterial growth through various mechanisms due to its high specific surface area and interaction with bacterial cell membranes; and chitosan exerts an antibacterial effect by binding to bacterial cell walls.

[0035] Preferably, in step S300, the ionic crosslinking reaction forms ionic bonds between the carboxyl groups in the alginate molecules and the metal ions in the crosslinking agent by adding an ionic crosslinking agent to the second mixed solution, thereby forming a network structure between the alginate molecules, thereby improving the mechanical strength and stability of the dressing; and the ionic crosslinking structure helps to regulate the swelling 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 dressing after ionic crosslinking has a certain stability in water, can continuously release antibacterial agents, and provide a sustained antibacterial effect.

[0036] Furthermore, the ionic crosslinking agent includes 5-10 wt% calcium chloride solution. By selecting calcium chloride solution as the ionic crosslinking agent, calcium ions (Ca 2+ ) and the negative charge in the alginate molecule (COO - ) forms a stable ionic network, improving the mechanical strength and stability of the dressing, making it less likely to break or deform under external forces; the concentration range of the calcium chloride solution is selected to be 5-10wt%, ensuring that the calcium chloride concentration can effectively cross-link the alginate, but not too high to cause excessive viscosity of the solution or the formation of an over-cross-linked network; the appropriate concentration ensures the efficient progress of the ionic cross-linking reaction and maintains good fluidity and operability of the final product. The temperature of the ionic cross-linking reaction is 20-30°C, and the reaction time is 1-2 hours. The appropriate temperature range ensures that the cross-linking reaction proceeds while avoiding high temperature damage to the polymer. Excessive temperature may cause unnecessary gel transformation of the temperature-responsive polymer, affecting the performance of the final dressing; the appropriate reaction time is sufficient for the calcium ions to form stable ionic bonds with the negative charges in the alginate molecules, ensuring the formation of a cross-linked network without excessive cross-linking. Excessive cross-linking time may result in excessive cross-linking, affecting the operability and flexibility of the dressing.

[0037] Preferably, the chemical cross-linking reaction forms a cross-linked network between the temperature-responsive polymer and the alginate molecules through covalent bonds by adding a chemical cross-linking agent, thereby enhancing the properties of the temperature-responsive polymer and enabling the dressing to undergo changes in physical properties according to changes in temperature, such as swelling or gelation, 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 be broken or damaged by external forces when treating wounds, but also improves the durability of the dressing, enabling it to withstand mechanical stress and environmental changes for a long time during use, reducing the need for repeated replacement.

[0038] Furthermore, the chemical cross-linking agent includes a 0.5~2wt% glutaraldehyde solution. Glutaraldehyde reacts with the temperature-responsive polymer (such as Pluronic F127 or polyethylene glycol-polypropylene glycol triblock copolymer) and the hydroxyl (-OH) or amine group (-NH2) in alginate through the active aldehyde group (-CHO) at the end to form covalent bonds, thereby constructing a cross-linked network, which significantly enhances the mechanical properties of the dressing, making it more durable and stable. Moreover, through chemical cross-linking, the structure of the dressing is more stable and less susceptible to the influence of the external environment, thereby extending the service life of the dressing. In addition, moderate chemical cross-linking can adjust the physical properties of the dressing, such as hardness, elasticity, and swelling, to ensure that the dressing can maintain sufficient flexibility and a certain degree of firmness during use. Finally, through appropriate chemical cross-linking, it can be ensured that the dressing has ideal adaptability when in contact with the wound, such as being able to maintain a certain shape and strength when needed, and gradually provide support during the healing process. The concentration of the glutaraldehyde solution is set at 0.5-2wt%. This concentration range helps ensure the appropriate cross-linking reaction. Excessive concentration may lead to excessive cross-linking, affecting the flexibility and workability of the dressing, while too low a concentration may lead to incomplete cross-linking, affecting the strength and stability of the dressing. The chemical cross-linking reaction temperature is 40-50°C, and the reaction time is 2-4 hours. The temperature and time of the chemical cross-linking reaction directly affect the efficiency and degree of cross-linking between glutaraldehyde, alginate, and the temperature-responsive polymer. The appropriate temperature ensures that glutaraldehyde can fully react with the polymer material without causing denaturation or degradation of the temperature-responsive polymer due to excessive temperature. Sufficient reaction time ensures the complete cross-linking reaction while avoiding irreversible changes in the polymer structure caused by excessive reaction time. This effectively controls the degree of cross-linking reaction, ensures the formation of a cross-linked network structure, and maintains the appropriate flexibility of the dressing. Excessive temperature and excessive reaction time may cause the dressing to be too hard or brittle, affecting its comfort and performance.

[0039] Preferably, 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 process is -50~-30℃, and the time is 10~14h; the temperature of the second freezing process is -30~-10℃, the vacuum degree is 5~50Pa, and the time is 20~26h. The purpose of the first pre-freezing process is to quickly cool the solution to -50~-30℃ so that the water therein freezes quickly, thereby controlling the freezing rate and ensuring that the water precipitates in the form of ice crystals without forming an overly large or uneven ice crystal structure; and within this temperature range, the water can freeze quickly, which will result in the ice crystal particles being smaller and more evenly distributed. The rapid freezing process of the water helps to reduce the time for 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, help to form 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-freeze for 10 to 14 hours to ensure that the water can be completely frozen and the ice crystals are fully distributed. Too short a time may result in incomplete freezing, affecting the subsequent freeze-drying effect; too long a time may cause instability of the polymer structure or over-freezing. Therefore, 10 to 14 hours is an optimized processing time.

[0040] For example, the purpose of the second freezing treatment stage is to remove moisture through the sublimation process. In this stage, the temperature is slightly increased to -30~-10℃, and it is carried out in a vacuum environment. The moisture can be directly converted from solid to gas, avoiding the formation of liquid water, thereby avoiding structural damage to the greatest extent. This process can effectively remove moisture while ensuring the maintenance of pores; the vacuum degree provides a low-pressure environment for sublimation, and low pressure helps to improve the efficiency of water conversion to gas and avoid an excessively long liquid phase; secondly, the sublimation process retains the pore structure formed by ice crystals, avoiding the shrinkage of the pores that may be caused by the evaporation of water. The long-term treatment ensures that the moisture in the dressing is completely removed, and no residual moisture will be left due to short-term treatment, ensuring the stability of the dressing and long-term storage.

[0041] Furthermore, after completely removing the water, the dressing will maintain a high porosity and an appropriate pore size. These pores contribute to the dressing's liquid absorption, enabling it to effectively absorb wound secretions, maintain a moist environment for the wound, and promote wound healing. A moderate pore size contributes to cell growth and the transport of nutrients, promoting wound healing. Preferably, the final alginate dressing has a porosity of 80-95% and a pore size of 50-200 μm. The appropriate porosity helps the dressing provide better water absorption and breathability in actual use, and the appropriate pore size adsorbs wound secretions and maintains a moist environment, helping to promote wound healing.

[0042] Preferably, in step S400, the alginate dressing is sterilized with gamma rays, effectively killing bacteria, viruses, fungi, and other microorganisms that may be present on and within the alginate dressing. High-energy gamma rays can destroy the DNA or RNA of microorganisms, preventing their reproduction or rendering them inactive, thereby achieving a sterilization effect. Due to their strong penetrating power, gamma rays can penetrate deep into the dressing, ensuring that even deep layers receive sufficient irradiation, ensuring comprehensive sterilization of the product.

[0043] Example 1

[0044] This embodiment provides an alginate dressing and a preparation method thereof. The alginate dressing comprises the following components in percentage by mass:

[0045] Sodium alginate: 60%, Pluronic F127: 20%, nanosilver: 2%, 8wt% calcium chloride solution: 2%, 1wt% glutaraldehyde solution: 1%, the balance is deionized water and inevitable impurities;

[0046] The preparation method comprises:

[0047] S100, dissolving alginate in deionized water to obtain a 5 wt % alginate solution; dissolving a temperature responsive polymer in deionized water to obtain a 10 wt % temperature responsive polymer solution; adding the temperature responsive polymer solution to the alginate solution and performing a first stirring process to form a first mixed solution;

[0048] S200, dispersing the antibacterial agent into the first mixed solution to obtain a second mixed solution;

[0049] S300, adding an ionic crosslinking agent to the second mixed solution, performing an ionic crosslinking reaction at a temperature of 25° C. for 1 hour, then adding a chemical crosslinking agent, performing a chemical crosslinking reaction at a temperature of 45° C. for 3 hours, and freeze-drying to obtain an alginate dressing;

[0050] S400, performing gamma-ray sterilization on the alginate dressing;

[0051] The freeze-drying process includes: a first pre-freezing process and a second freezing process;

[0052] The first pre-freezing treatment temperature is -40°C and the time is 12h;

[0053] The second freezing treatment was performed at a temperature of -20°C, a vacuum degree of 15 Pa, and a time of 24 h.

[0054] Example 2

[0055] This embodiment provides an alginate dressing and a preparation method thereof. The alginate dressing comprises the following components in percentage by mass:

[0056] Sodium alginate: 70%, polyethylene glycol-polypropylene glycol triblock copolymer: 10%, nanosilver: 0.1%, 10wt% calcium chloride solution: 1%, 2wt% glutaraldehyde solution: 0.5%, the balance is deionized water and inevitable impurities;

[0057] The preparation method comprises:

[0058] S100, dissolving alginate in deionized water to obtain an 8 wt % alginate solution; dissolving polyethylene glycol-polypropylene glycol triblock copolymer in deionized water to obtain a 15 wt % polyethylene glycol-polypropylene glycol triblock copolymer solution; adding the temperature responsive polymer solution to the alginate solution, performing a first stirring process, and forming a first mixed solution;

[0059] S200, dispersing the antibacterial agent into the first mixed solution to obtain a second mixed solution;

[0060] S300, adding an ionic crosslinking agent to the second mixed solution, performing an ionic crosslinking reaction at a temperature of 30° C. for 1 hour, then adding a chemical crosslinking agent, performing a chemical crosslinking reaction at a temperature of 50° C. for 2 hours, and freeze-drying to obtain an alginate dressing;

[0061] S400, performing gamma-ray sterilization on the alginate dressing;

[0062] The freeze-drying process includes: a first pre-freezing process and a second freezing process;

[0063] The first pre-freezing treatment temperature is -30°C and the time is 10h;

[0064] The second freezing treatment was performed at a temperature of -10°C, a vacuum degree of 10 Pa, and a time of 20 h.

[0065] Example 3

[0066] This embodiment provides an alginate dressing and a preparation method thereof. The alginate dressing comprises the following components in percentage by mass:

[0067] Sodium alginate: 50%, Pluronic F127: 30%, nanosilver: 5%, 5wt% calcium chloride solution: 5%, 0.5wt% glutaraldehyde solution: 2%, the balance is deionized water and inevitable impurities;

[0068] The preparation method comprises:

[0069] S100, dissolving alginate in deionized water to obtain a 3 wt % alginate solution; dissolving a temperature responsive polymer in deionized water to obtain a 5 wt % temperature responsive polymer solution; adding the temperature responsive polymer solution to the alginate solution and performing a first stirring process to form a first mixed solution;

[0070] S200, dispersing chitosan into the first mixed solution to obtain a second mixed solution;

[0071] S300, adding an ionic crosslinking agent to the second mixed solution, performing an ionic crosslinking reaction at a temperature of 20° C. for 2 hours, then adding a chemical crosslinking agent, performing a chemical crosslinking reaction at a temperature of 40° C. for 4 hours, and freeze-drying to obtain an alginate dressing;

[0072] The freeze-drying process includes: a first pre-freezing process and a second freezing process;

[0073] The first pre-freezing treatment temperature is -50°C and the time is 14h;

[0074] The second freezing treatment was performed at a temperature of -30°C, a vacuum degree of 45 Pa, and a time of 26 h.

[0075] Comparative Example 1

[0076] This comparative example provides an alginate dressing and a preparation method thereof. The alginate dressing comprises the following components in percentage by mass:

[0077] Sodium alginate: 60%, Pluronic F127: 20%, nanosilver: 2%, 8wt% calcium chloride solution: 2%, the balance is deionized water and inevitable impurities;

[0078] The preparation method is the same as that of Example 1, except that no chemical cross-linking agent is added in step S300.

[0079] Comparative Example 2

[0080] This comparative example provides an alginate dressing and a preparation method thereof. The alginate dressing comprises the following components in percentage by mass:

[0081] Sodium alginate: 60%, Pluronic F127: 20%, nanosilver: 2%, 1wt% glutaraldehyde solution: 1%, the balance is deionized water and inevitable impurities;

[0082] The preparation method is the same as that of Example 1, except that no ionic crosslinking agent is added in step S300.

[0083] Comparative Example 3

[0084] This comparative example provides an alginate dressing and a preparation method thereof. The alginate dressing comprises the following components in percentage by mass:

[0085] Sodium alginate: 60%, Pluronic F127: 20%, nanosilver: 2%, the balance is deionized water and inevitable impurities;

[0086] The preparation method is the same as that of Example 1, except that no ionic crosslinking agent or chemical crosslinking agent is added in step S300.

[0087] Comparative Example 4

[0088] This comparative example provides an alginate dressing and a preparation method thereof. The alginate dressing is purchased from outside.

[0089]

Experimental data

[0090] The alginate dressings of Examples 1-3 and Comparative Examples 1-4 were tested as follows. The results are shown in Table 1:

[0091] Table 1

[0092]

[0093] Tensile Strength Test: Cut the alginate dressings of Examples 1-3 and Comparative Examples 1-4 into dumbbell-shaped specimens with a length of 75 mm, a narrow width of 5 mm, and a thickness of 2 mm. Clamp the specimens at both ends and operate the tester until they break. The clamp spacing is 50 mm and the tensile speed is 10 mm / min. The maximum load (F, in Newtons) and cross-sectional area at break (A, in mm²) are recorded, and the tensile strength is calculated.

[0094] Liquid absorption rate test: Cut 2 cm × 2 cm square specimens (area S) of the alginate dressings of Examples 1-3 and Comparative Examples 1-4, dry and weigh the initial weight W0, and completely immerse the specimens in the solution. Record the liquid absorption W at time t of 5, 10, and 30 min respectively. t , and calculate the liquid absorption rate.

[0095] Glutaraldehyde residue detection: 1 g of the alginate dressings of Examples 1-3 and Comparative Examples 1-4 was chopped into small pieces, added with 10 mL of a 1:1 acetonitrile-water mixed solvent, and subjected to ultrasonic extraction for 30 min. The mixture was centrifuged (10,000 rpm, 10 min), and the supernatant was filtered (0.22 μm membrane). The residue was calculated by HPLC using the external standard method.

[0096] Antibacterial rate test: Staphylococcus aureus and Escherichia coli were inoculated into nutrient broth, cultured at 37°C for 18 h, and the concentration was adjusted to 1×10 6CFU / mL, 1 cm of the dressings of Examples 1-3 and Comparative Examples 1-4 were co-cultured with 1 mL of bacterial solution (37°C, 24 h), 100 μL of the mixed solution was diluted gradiently, spread on agar plates, and cultured at 37°C for 24 h, and the surviving colonies (N t ), and the inhibition rate was calculated.

[0097] As can be seen from the above table, due to the double cross-linked network, the tensile strength of Examples 1-3 is significantly higher than that of the comparative example. 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 to 3 times that of Comparative Example 4; the residual amount of Examples 1-3 is controlled to ≤0.1ppm by γ-ray sterilization, which meets medical standards; the antibacterial rate of Examples 1-3 is much higher than that of Comparative Example 1-4.

[0098] Drug release rate test: The alginate dressings of Examples 1-3 and Comparative Examples 1-4 were cut into 1 cm diameter discs, accurately weighed m, and immersed in a small amount of pH 7.4 phosphate buffer for 30 minutes, placed in a dialysis bag, sealed, and immersed in a conical flask filled with pH 7.4 phosphate buffer. The flask was kept in a constant temperature oscillation at 37±0.5°C and a speed of 50-100 rpm. 1-2 mL of the supernatant was collected at 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h, respectively. The supernatant was detected by high performance liquid chromatography and the drug release rate was calculated. The results are shown in Table 2. Figure 1 shown.

[0099] Table 2

[0100]

[0101] From Table 2 Figure 1 It can be seen that Examples 1-3 release the drug slowly within 1-6 hours, less than 30%, reflecting the initial controlled release ability; after 12 hours, the drug release rate is significantly increased to 45~50%, and 70~77% in 24 hours, indicating that the temperature-responsive polymer undergoes a phase change at body temperature, triggering accelerated drug release, and adapting to the treatment needs of infection with fever greater than 38°C; while in Comparative Example 1, only ionic crosslinking lacks a chemical crosslinking network, and the burst release rate is as high as 20.3%, and the 24-hour drug release rate is 92.3%, indicating that single crosslinking cannot effectively control release; Comparative Example 2 has only chemical crosslinking, and the initial burst release is 18.5%, which is lower than Comparative Example 1, but due to the lack of rapid gelation of ionic crosslinking, the drug diffusion resistance is insufficient, and the 24-hour drug release rate is still as high as 85.6%; Comparative Example 3 has no crosslinking, and the drug is released 35% within 1 hour and 98.5% in 24 hours, confirming that the uncrosslinked material cannot form an effective controlled release barrier; compared with commercially available products, the traditional alginate dressing has a 24-hour drug release rate of 90.5%, and has no temperature response characteristics, demonstrating the significant advantages of the present invention in intelligent controlled release.

[0102] 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. The samples were then dried in a vacuum drying oven at 60°C for 24 h to remove residual moisture. The porosity and pore size were measured by mercury intrusion porosimetry. The results are shown in Table 3.

[0103] Table 3

[0104]

[0105] The double cross-linked network of Examples 1-3 stabilizes the ice crystal growth framework during the freeze-drying process, avoids drying collapse, and forms a high-porosity structure, and the high porosity directly improves the liquid absorption rate; while Comparative Example 1 is only ion cross-linked, and due to the lack of a chemical cross-linked network, part of the structure collapses during freeze-drying, and the closed-cell ratio is high, resulting in a decrease in the liquid absorption rate; Comparative Example 2 is only chemically cross-linked, and excessive cross-linking with glutaraldehyde causes the polymer chains to stack tightly, forming a microporous structure, which hinders the rapid penetration of liquid; Comparative Example 3 has no cross-linking, cannot maintain the freeze-dried skeleton, and cannot form a porous structure; Comparative Example 4 is prone to disintegration after macropore absorption.

[0106] Throughout this specification, terms such as "one embodiment," "some embodiments," and "specific embodiments" mean that the specific features, structures, materials, or characteristics described in conjunction with that embodiment or example are included in at least one embodiment or example of the present invention. In this specification, schematic representations of these terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

[0107] 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 scope of protection of the present invention should be based on 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 being deionized water and unavoidable impurities; The alginate dressing has a double cross-linked network, wherein the ionic cross-linking agent and the alginate form a first network through ionic bonds, and 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 to 10 wt%; the chemical crosslinking agent includes a glutaraldehyde solution with a mass concentration of 0.5 to 2 wt%; the alginate includes sodium alginate; and the temperature-responsive polymer includes Pluronic F127; The preparation method of 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 and performing a first stirring process to form 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.

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 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.

5. The alginate dressing according to claim 1, characterized in that The freeze-drying process in step S300 includes: a first pre-freezing process and a second freezing process; The first pre-freezing treatment is performed at a temperature of -50 to -30°C for 10 to 14 hours; The temperature of the second freezing treatment is -30 to -10°C, the vacuum degree is 5 to 50 Pa, and the time is 20 to 26 hours.

6. The alginate dressing according to claim 1, characterized in that 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 %.

7. The alginate dressing according to claim 1, characterized in that After step S300, the method further includes: S400: performing gamma-ray sterilization on the alginate dressing.

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