Zinc-loaded eutectic gel as well as preparation method and application thereof

Abstract

The invention relates to the field of biomedical polymer materials, and discloses zinc-loaded eutectic gel as well as a preparation method and application thereof. The zinc-loaded eutectic gel comprises the following components: gelatin, polyvinyl alcohol and a deep eutectic solvent containing zinc ions. The preparation method comprises the following steps: dissolving gelatin and polyvinyl alcohol in water, and reacting to obtain gelatin-polyvinyl alcohol hydrogel; and placing the gelatin-polyvinyl alcohol hydrogel in a deep eutectic solvent containing zinc ions for replacement to obtain the zinc-loaded eutectic gel. The tensile strength and the fracture strain of the zinc-loaded eutectic gel can reach 258kPa and 632% at most, and meanwhile, the zinc-loaded eutectic gel has good low-temperature stability and still keeps a phase-change-free state in an environment of-80 DEG C. The zinc-loaded eutectic gel can effectively antagonize bacterial infection, inhibit inflammatory response, control moisture volatilization, promote angiogenesis and collagen generation and accelerate wound healing, and is suitable for the medical fields of infectious and non-infectious wound dressings, joint wound dressings and the like.

Description

Technical Field

[0001] The present invention relates to the field of biomedical polymer materials, and more particularly to a zinc-loaded eutectic gel and a preparation method and application thereof. Background Art

[0002] Hydrogels, as functional polymer materials with widespread applications in biomedicine, flexible electronics, and tissue engineering, have attracted widespread attention in recent years due to their excellent water retention, biocompatibility, and tunable mechanical properties. In particular, in wound dressing applications, hydrogels, with their soft, moisturizing, and cooling properties, can provide a favorable wound microenvironment and significantly promote tissue healing. Gelatin, a natural polymer derived from collagen hydrolysis, exhibits excellent biocompatibility and degradability, making it widely used in the preparation of hydrogels. However, hydrogels constructed solely from gelatin often suffer from issues such as unstable gel networks, poor mechanical strength, structural collapse, and inability to function in extremely cold environments, making them unable to meet the mechanical support and environmental stability requirements for complex wound repair. Furthermore, in the treatment of infectious wounds, hydrogels are required to meet stringent requirements for comprehensive performance, including antimicrobial activity, low-temperature stability, low cytotoxicity, and angiogenesis promotion. Designing hydrogels that possess multiple functionalities (such as moisture retention, freeze-resistance, antimicrobial properties, and tissue regeneration promotion) while also balancing mechanical properties and biosafety has become a major research challenge in the field of gel materials.

[0003] In response to the technical shortcomings of insufficient mechanical properties and lack of multifunctionality of hydrogels, several existing technologies have attempted to improve them. For example, patent CN113354953A proposes a flexible conductive biopolymer material and a preparation method thereof, which uses a deep eutectic solvent as a plasticizer to improve the flexibility of the biopolymer, and improves the mobility of the molecular chain by reconstructing the hydrogen bond network, thereby improving the ductility of the flexible material. This solution focuses on improving the flexibility of the material and developing conductive properties for use in the field of flexible electronics, but it does not consider the biological functions required for wound healing of the material, especially the lack of antibacterial and cell compatibility tests, which limits its application in wound dressings. Patent CN115536867A discloses a nano zinc oxide hydrogel, which achieves dispersion and stabilization of nano zinc oxide by introducing zinc oxide into a ternary deep eutectic solvent of urea-choline chloride-acrylamide and performing in-situ heat treatment, further inducing polymerization to form a hydrogel. This solution takes into account both conductive properties and antibacterial functions, and avoids the use of organic solvents in the preparation process, and has certain green chemical advantages. However, this method has high requirements for the purity of raw materials, and the preparation process of nano zinc oxide is complicated. There are still problems such as long preparation cycle and high cost, and its performance retention ability in low temperature environment is not reflected. Patent CN116217980A proposes a eutectic gel with biosensing and antibacterial properties, using choline chloride-glycerol-zinc chloride ternary system as a deep eutectic solvent, combined with N-hydroxyethyl acrylamide as a monomer, and polymerized under ultraviolet conditions to obtain a gel material with conductive, sensing and antibacterial properties. However, this method focuses on the field of flexible sensors, and has not been deeply developed and verified in terms of anti-drying / antifreezing ability, biocompatibility, angiogenesis, etc. in wound healing, and its scope of application is still limited.

[0004] In summary, although the existing eutectic gel schemes have made significant progress in flexibility, conductivity, antibacterial or sensing, a eutectic gel system that comprehensively combines biosafety, mechanical strength, low-temperature stability and multiple therapeutic functions (such as antibacterial and healing promotion) has not yet been reported. Summary of the Invention

[0005] The present invention provides a zinc-loaded eutectic gel to overcome the defects of the hydrogels described in the prior art in wound repair, such as weak antibacterial properties, low mechanical strength, poor low-temperature stability, and insufficient ability to promote tissue regeneration.

[0006] Another object of the present invention is to provide a method for preparing zinc-loaded eutectic gel;

[0007] Another object of the present invention is to provide an application of the zinc-loaded eutectic gel.

[0008] In order to solve the above technical problems, the technical solutions of the present invention are as follows:

[0009] A zinc-loaded eutectic gel comprises gelatin, polyvinyl alcohol and a deep eutectic solvent containing zinc ions.

[0010] Preferably, the deep eutectic solvent further comprises ethylene glycol and betaine.

[0011] Preferably, the zinc ions are introduced as zinc chloride.

[0012] Preferably, the gel strength of the gelatin is not less than 250 Bloom; the molecular weight of the polyvinyl alcohol is 89,000 to 98,000, and the degree of hydrolysis is not less than 99%.

[0013] Furthermore, in the deep eutectic solvent containing zinc ions, the zinc ions are introduced in the form of zinc chloride, and the mass fraction of zinc chloride is no more than 0.2%.

[0014] Preferably, the mass fraction of zinc chloride is less than 0.2%.

[0015] Preferably, the mass fraction a of zinc chloride is: 0.1%≤a<0.2%.

[0016] Furthermore, the mass ratio of gelatin to polyvinyl alcohol in the zinc-loaded eutectic gel is 1:0.3-0.4.

[0017] Preferably, the mass ratio of gelatin to polyvinyl alcohol in the zinc-loaded eutectic gel is 1:0.3.

[0018] A method for preparing the zinc-loaded eutectic gel comprises the following steps: dissolving gelatin and polyvinyl alcohol in water to obtain a gelatin-polyvinyl alcohol hydrogel after reaction; and placing the gelatin-polyvinyl alcohol hydrogel in a deep eutectic solvent containing zinc ions for solvent replacement to obtain a zinc-loaded eutectic gel.

[0019] Preferably, gelatin and polyvinyl alcohol are dissolved in water at 90-95°C.

[0020] Preferably, the gelatin-polyvinyl alcohol hydrogel is obtained after the reaction at 4-15°C.

[0021] An application of the zinc-loaded eutectic gel is to prepare a product for protecting wounds and / or promoting wound healing.

[0022] Preferably, the products include wound moisturizing products and dressings.

[0023] An application of the zinc-loaded eutectic gel is to prepare a product for inhibiting bacterial growth, wherein the bacteria include but are not limited to Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii.

[0024] An application of the zinc-loaded eutectic gel is used to prepare a product for inhibiting the expression of inflammatory factors, including TNF-α and IL-6.

[0025] An application of the zinc-loaded eutectic gel is used to prepare products that promote the generation of blood vessels and collagen.

[0026] An application of the zinc-loaded eutectic gel is to prepare a product that promotes the expression of CD31 (endothelial-specific marker) and α-SMA (vascular smooth muscle cell marker).

[0027] An application of the zinc-loaded eutectic gel is to prepare a product suitable for protecting wounds and / or promoting wound healing at -80 to 40°C.

[0028] Preferably, it is a product for moisturizing wound surfaces.

[0029] Preferably, the products include but are not limited to wound moisturizing products, wound dressings, and elastic hydrogel bandages.

[0030] Preferably, the dressing includes elastic dressing for wounds on joints for joint mobility rehabilitation and dressing for wounds in extreme cold environments;

[0031] Preferably, the elastic hydrogel bandage is suitable for use in normal temperature and extreme cold environments, and is used for the pressure prevention and treatment of early hypertrophic scars.

[0032] During the preparation of the anti-drying and anti-freezing zinc-loaded eutectic gel of the present invention, gelatin molecules undergo a sol-gel transition, and the molecular chains approach to form a helical structure, thereby obtaining a gelatin-polyvinyl alcohol hydrogel. The gelatin-polyvinyl alcohol hydrogel is then immersed in a deep eutectic solvent in which zinc ions are dissolved. During the solvent replacement process, water molecules are exchanged into the deep eutectic solvent, and the ethylene glycol molecules of the deep eutectic solvent hydrogen bond with the gelatin and polyvinyl alcohol molecules, while the zinc ions promote the aggregation of macromolecular chains through the Hofmeister effect, thereby improving the mechanical properties of the obtained zinc-loaded eutectic gel. In addition to the antibacterial effect of zinc ions, the strengthening effect of zinc ions on the gel comes from the Hofmeister effect (salting-out effect), that is, the effect of specific ions on a specific gel network. However, this effect has ion selectivity and concentration dependence, and different ions or different concentrations can also produce negative effects that weaken the network structure. With the help of the Hofmeister effect, zinc ions can induce the aggregation of polymer chain segments in the system of the present invention (a specific concentration of zinc ions and a specific concentration of polymer network), promote the formation of a three-dimensional network, and thus enhance the structural density and mechanical properties of the gel.

[0033] By regulating the ratio between zinc ion concentration and the polymer system, this invention achieves a synergistic improvement and regulation of antibacterial properties, biocompatibility, mechanical strength, and antifreeze properties, rather than simply adding these functions together. This material system, based on molecular design and optimized physical cross-linking mechanisms, demonstrates superior overall performance compared to traditional hydrogels in the application scenario of infected wound repair, representing a substantial advancement.

[0034] Compared with the prior art, the beneficial effects of the technical solution of the present invention are:

[0035] 1. Significantly enhanced mechanical properties. By introducing zinc ions into the gelatin-polyvinyl alcohol eutectic gel network, the structural strength and flexibility of the gel are significantly improved. Compared with the eutectic gel without zinc ions, the tensile strength increased by about 8.90 times and the fracture strain increased by about 3.62 times after the addition of zinc ions. At the specific concentrations of polyvinyl alcohol and zinc ions of the present invention, the maximum tensile strength of the gel can reach 258kPa and the maximum fracture strain can reach 632%, showing excellent flexibility and stretchability.

[0036] 2. Excellent low-temperature stability. The prepared eutectic gel does not undergo phase change in an environment as low as -80°C and has excellent antifreeze properties, providing material support for its application as a wound dressing in cold or extreme environments.

[0037] 3. Biological function of promoting wound repair. In the infectious wound model, the zinc-loaded eutectic gel can effectively inhibit the expression of inflammatory factors (such as TNF-α and IL-6), promote angiogenesis (by upregulating the expression of CD31 and α-SMA) and collagen deposition, accelerate the closure of the wound, and significantly improve the quality of healing. The zinc-loaded eutectic gel of the present invention has good compatibility and low toxicity to fibroblasts and is suitable for use as a medical material that directly contacts the wound. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 Schematic diagram of the preparation and application of zinc-loaded eutectic gel, a is the preparation process of zinc-loaded eutectic gel, b is the process of promoting wound healing;

[0039] Figure 2 Figure 2 shows the changes in mechanical properties of zinc-loaded eutectic gel at different polyvinyl alcohol contents (ac) and zinc ion contents (df), including stress-strain curves, tensile strength and fracture strain, and elastic modulus comparisons.

[0040] Figure 3 The structural analysis and element distribution characteristics of zinc ion eutectic gel, a is FTIR infrared spectrum, b is XRD spectrum, c is DSC spectrum, d and e are Zn 2+ Distribution of zinc in eutectic gels with concentrations of 0.1% and 0.2%;

[0041] Figure 4 is the cell compatibility of zinc eutectic gel with different PVA contents and different zinc ion concentrations, ad is the quantitative analysis of cell activity, i, ii, iii in e represent Zn 2+Cell live-death staining of gels with concentrations of 0, 0.1%, and 0.2% in an extract with a concentration of 0.01 g / mL; i, ii, and iii in f represent Zn 2+ Live-dead staining images of cells with gel concentrations of 0, 0.1%, and 0.2% in an extract concentration of 0.1 g / mL;

[0042] Figure 5 Figure 3. Antibacterial properties of zinc eutectic gel against Staphylococcus aureus at different zinc ion concentrations. (a) is the antibacterial growth curve, (b) is the bacterial survival rate, (c) is the plate culture result, and (d) is the scanning electron microscopy image.

[0043] Figure 6 Figure 3 shows the antibacterial properties of zinc eutectic gel against Escherichia coli at different zinc ion concentrations. Figure a is the antibacterial growth curve, b is the bacterial survival rate, c is the plate culture result, and d is the scanning electron microscopy image.

[0044] Figure 7 The wound healing effect of zinc-loaded eutectic gel, a is the photos of treatment on days 0, 4, 7, 10, and 13, b is the wound contraction trajectory, and c is the wound closure rate;

[0045] Figure 8 This is the histopathological analysis of the repair effect of zinc-loaded eutectic gel on wound tissue, a is HE staining, b is Masson trichrome staining;

[0046] Figure 9 Immunofluorescence staining of the wound surface after treatment with zinc-loaded eutectic gel, a for TNF-α and IL-6, b for CD31 and α-SMA. DETAILED DESCRIPTION

[0047] The present invention will be further described below in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0048] Unless otherwise specified, the reagents and materials used in the following examples were commercially available.

[0049] In the following embodiments, the gel strength of the gelatin is not less than 250 Bloom; the molecular weight of the polyvinyl alcohol is 89,000 to 98,000, and the degree of hydrolysis is not less than 99%.

[0050] Example 1

[0051] A total mass of 1g of PVA and gelatin (mass ratio of 1:0.3) was dissolved in 10g of water with stirring at 90°C for 30 minutes to form a transparent, homogeneous solution. The solution was left at 4°C for 10 minutes to allow the initial formation of a hydrogel. The hydrogel was then immersed in a deep eutectic solvent containing ethylene glycol and betaine (mass ratio of ethylene glycol to betaine was 4:1) and ZnCl (0.1g / 100g DES) was added. The hydrogel was immersed for 4 hours to obtain a zinc-loaded eutectic gel (Zn-0.1).

[0052] Example 2

[0053] The technical solution of Example 2 is similar to that of Example 1, except that, in Example 2, 1 g of PVA and gelatin (mass ratio of 1:0.4) are dissolved in 10 g of water at 90° C. with stirring for 30 minutes to form a transparent uniform solution.

[0054] Example 3

[0055] The technical solution of Example 3 is similar to that of Example 1, except that the amount of zinc chloride added to the deep eutectic solvent in Example 3 is 0.2 g / 100 g DES (Zn-0.2).

[0056] Comparative Example 1

[0057] The technical solution of Comparative Example 1 is similar to that of Example 1, except that zinc ions (Zn-0) are not added to the deep eutectic solvent of Comparative Example 1.

[0058] Comparative Example 2

[0059] The technical solution of Comparative Example 2 is similar to that of Example 1, except that the mass ratios of gelatin to polyvinyl alcohol in Comparative Example 2 are 1:0.1 and 1:0.2.

[0060] Detection method

[0061] The chemical structure of the gel was analyzed using Fourier transform infrared spectroscopy; the amorphous structure of the gel was analyzed using X-ray diffraction; the phase transition of the gel at low temperature was measured using differential scanning calorimetry; the elemental distribution of the gel was measured using an energy dispersive spectrometer; the mechanical properties of the gel were measured using a material testing machine; the biocompatibility of the gel was measured using CCK-8 and live-dead cell staining; the antibacterial properties of the gel were measured using the dilution coating plate method, and the bacterial morphology was observed using a scanning electron microscope; the pro-healing properties of the gel were detected using a mouse model of wound infection; hematoxylin-eosin (HE) staining and Masson staining were used to evaluate the pathological changes and collagen deposition of the wound tissues in different groups, respectively; and immunofluorescence staining was used to detect inflammatory factors and angiogenesis in the wound.

[0062] Analysis

[0063] according to Figure 1 The zinc-loaded eutectic gel was prepared by process a. Figure 1 b process verifies its actual effect in the repair of infected wounds.

[0064] Figure 2 The results show that when the PVA content is 30% to 40% (Examples 1 and 2), PVA plays a significant role in enhancing the mechanical properties of the zinc-loaded eutectic gel, with the tensile strength and fracture strain reaching the optimum, and the elastic modulus increasing ( Figure 2 ac). Example 1 has a tensile strength of 280.1 kPa and a strain at break of 603%, while Comparative Example 1 has a tensile strength of 29.2 kPa and a strain at break of 174%. The tensile strength and strain at break of Example 1 are 8.90 times and 3.62 times those of Comparative Example 1, respectively, demonstrating a significant reinforcement effect. A PVA content that is too low (Comparative Example 2) is detrimental to network formation or structural integrity, resulting in significantly reduced mechanical properties.

[0065] In addition, Zn 2+ By enhancing the molecular chain aggregation force through the Hofmeister effect, the tensile strength and strain of the zinc-loaded eutectic gel are improved. 2+ When the concentration is too high (Example 3), the solubility reaches saturation, which will also inhibit the network expansion and lead to weakened mechanical properties. Figure 2 d It can be seen that without adding Zn 2+ The mechanical properties of the eutectic gel are extremely weak, and when the amount of zinc chloride increases to 0.2g, the mechanical properties also decrease significantly. Figure 2 It can be seen from e that the tensile strengths of the gels corresponding to Zn-0, Zn-0.1 and Zn-0.2 are 29.2 kPa, 280.1 kPa and 18.1 kPa, respectively, and the corresponding fracture strains are 174%, 603% and 204%, respectively. Figure 2 As shown in Figure f, the elastic modulus of the eutectic gel of Zn-0 is 21.3 kPa, while the elastic modulus of the eutectic gel of Zn-0.2 is reduced to 11.2 kPa. 2+ The addition of Zn can promote the aggregation of molecular chains through the Hofmeister effect. Therefore, the mechanical properties of Zn-0.1 are much better than those of Zn-0 eutectic gel. The sharp decline in the mechanical properties of Zn-0.2 may be due to excessive aggregation of molecular chains, resulting in microphase separation, thereby weakening the mechanical properties.

[0066] Figure 3 FTIR and XRD showed that Zn 2+ Enhances the hydrogen bonding between gelatin and PVA molecular chains and the stability of the gel network structure ( Figure 3ab). Comparative Example 1 shows an obvious phase transition endothermic peak at 0°C, while Example 1 has almost no phase transition peak, indicating that the zinc-loaded eutectic gel maintains a stable amorphous state between -80°C and 40°C and has excellent antifreeze properties ( Figure 3 c). Figure 3 The Zn element in de is evenly dispersed, indicating that Zn 2+ Successfully introduced and stably distributed in the gel network (Example 1, Example 3).

[0067] Figure 4 ab shows that PVA has no obvious toxicity to cells. The cell activity is above 90% at different PVA contents. The cell survival rate in Example 1 reaches 102.6%. Figure 4 c) All different Zn 2+ The cell activity of the content was above 90%, and in the high concentration extract ( Figure 4 d), Zn 2+ When the content was increased (Example 3), the cell activity dropped to about 60%, and there was a slight risk of cytotoxicity. Figure 4 ef shows that the low concentration of the extract ( Figure 4 e), all different Zn 2+ The number of live / dead cells in the high concentration extract was basically the same, while in the high concentration extract ( Figure 4 f), Zn 2+ The content increased (Example 3), and the number of dead cells increased, indicating that too high a concentration of zinc ions would be detrimental to cell survival.

[0068] Figure 5 In ac, Zn 2+ The addition of significantly inhibited the growth of Staphylococcus aureus, with the inhibition rate of Example 1 being 99.996%, while that of Comparative Example 1 was 57.65%. Figure 5 In d, the bacterial surface of comparative example 1 is round and complete, while that of Zn 2+ The addition of iodine causes the bacterial cell membrane to shrink and rupture. Figure 6 In ac, Zn 2+ The addition of significantly inhibited the growth of E. coli, with the inhibition rate of Example 1 being 74.37% and that of Comparative Example 1 being 50.21%. Figure 6 In d, the bacterial surface of comparative example 1 is round and complete, while that of Zn 2+ The addition of zinc eutectic gel caused the bacterial surface to wrinkle and collapse. The above results show that the zinc-loaded eutectic gel of the present invention has a broad-spectrum antibacterial ability.

[0069] The wounds were treated with Comparative Example 1, Example 3, and Example 1, respectively. The wound healing rates on the 4th day were 30.5%, 58.0%, and 60.4%, respectively. The wound healing rates on the 7th day were increased to 77.2%, 81.9%, and 88.7%, respectively. Example 1 and Example 3 were significantly better than the control group and Comparative Example 1 throughout the healing period. They had a fast healing speed and a high degree of closure, showing the best wound repair effect ( Figure 7 ac).

[0070] Compared with the control group and comparative example, the inflammatory cells in the wound tissue of the embodiment group were significantly reduced ( Figure 8 a), indicating that it has a good anti-inflammatory effect. At the same time, the new granulation tissue grows faster, reflecting a stronger tissue regeneration ability. The wound collagen fibers of the Example group increased significantly, and interstitial edema was relieved faster, which accelerated the formation of new epithelium and the reconstruction of skin structure ( Figure 8 b) The above results show that the zinc-loaded eutectic gel of the present invention has excellent healing-promoting properties and can effectively improve the quality and efficiency of wound repair.

[0071] The results of immunofluorescence staining on day 7 showed that ( Figure 9 a), compared with the control group and comparative example 1, the example group significantly inhibited the expression of inflammatory factors TNF-α and IL-6, and the inflammation level in the wound tissue was significantly reduced, indicating that the zinc-loaded eutectic gel of the present invention has good anti-inflammatory regulatory ability. Further on the 13th day, the immunofluorescence staining analysis of angiogenesis-related markers CD31 and α-SMA found that ( Figure 9 b) The new blood vessels in the Example group showed more regular structure, more orderly arrangement, and higher blood vessel density, significantly outperforming the control group and Comparative Example 1. This demonstrates the significant advantages of the zinc-loaded eutectic gel in promoting angiogenesis and accelerating tissue reconstruction. This further validates its multiple functionalities in the repair of infected wounds, including synergistic effects of anti-inflammatory, angiogenesis-promoting, and tissue regeneration.

[0072] Obviously, the above embodiments of the present invention are merely examples for the purpose of clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Those skilled in the art will appreciate that other variations or modifications can be made based on the above description. It is not necessary and impossible to enumerate all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the claims of the present invention.

Claims

1. A zinc-loaded eutectic gel, characterized in that: The components include gelatin, polyvinyl alcohol, and a deep eutectic solvent containing zinc ions.

2. The zinc-loaded eutectic gel according to claim 1, characterized in that In the deep eutectic solvent containing zinc ions, the zinc ions are introduced in the form of zinc chloride, and the mass fraction of zinc chloride is no more than 0.2%.

3. The zinc-loaded eutectic gel according to claim 1, characterized in that The mass ratio of gelatin to polyvinyl alcohol in the zinc-loaded eutectic gel is 1:0.3-0.

4.

4. A method for preparing the zinc-loaded eutectic gel according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: dissolving gelatin and polyvinyl alcohol in water to obtain a gelatin-polyvinyl alcohol hydrogel after reaction; placing the gelatin-polyvinyl alcohol hydrogel in a deep eutectic solvent containing zinc ions for solvent replacement to obtain a zinc-loaded eutectic gel.

5. Use of the zinc-loaded eutectic gel according to any one of claims 1 to 3, characterized in that: Used to prepare products for protecting wounds and / or promoting wound healing.

6. The use of the zinc-loaded eutectic gel according to claim 5, characterized in that: Used for preparing products that inhibit bacterial growth, including but not limited to Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii.

7. The use of the zinc-loaded eutectic gel according to claim 5, characterized in that: Used to prepare products that inhibit the expression of inflammatory factors, including TNF-α and IL-6.

8. The use of the zinc-loaded eutectic gel according to claim 5, characterized in that: Used to prepare products that promote angiogenesis and collagen production.

9. The use of the zinc-loaded eutectic gel according to claim 8, characterized in that: Used to prepare products that promote the expression of CD31 and α-SMA.

10. Use of the zinc-loaded eutectic gel according to any one of claims 1 to 3, characterized in that: Used to prepare products suitable for protecting wounds and / or promoting wound healing at -80 to 40°C.

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