A chronic ulcer wound repair gel and methods of making and using same

Abstract

The application discloses a chronic ulcer wound repairing gel and a preparation method and application thereof, and belongs to the technical field of medical materials. Since bacterial cellulose has the advantages of good biocompatibility, high water retention and moisturizing capacity, strong mechanical property, good air permeability, low toxicity and the like, the bacterial cellulose is used to prepare the bacterial cellulose-based chronic ulcer wound repairing gel capable of promoting chronic wound healing by compounding functional components. The gel can bidirectionally regulate the wet balance of a wound surface; contains a large amount of hydroxyl groups, can highly retain water, has an ice-cool feeling, effectively relieves pain, simultaneously reduces irritation to a wound and a mucous membrane, reduces the sensitivity of exposed nerves, and reduces pain; the photosensitizer in the gel can inhibit bacterial infection by irradiation of near-infrared laser; active components can inhibit inflammatory diffusion, promote collagen deposition and angiogenesis, and the like, so as to promote the healing of a chronic ulcer wound surface.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, specifically relating to a chronic ulcer wound repair gel, its preparation method, and its application. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] In recent years, the aging population trend has become increasingly apparent. This aging population will increase the demand for healthcare, and the problem of pressure ulcers caused by prolonged bed rest in the elderly deserves serious attention. Pressure ulcers, also known as pressure sores, are caused by prolonged pressure, friction, or shearing, leading to impaired blood supply and tissue malnutrition. These ulcers are common in patients with limited mobility, sensory impairment, or coma, who are unable to perceive or respond to the body's need for periodic repositioning. When tissue compression exceeds capillary pressure, prolonged pressure or shearing can lead to ischemia. Skin necrosis is caused by tissue hypoxia and ischemia-reperfusion injury, particularly affecting bony prominences such as the sacrum, buttocks, and ankles, often appearing after two hours of inactivity. The presence of inflammatory cytokines, excessive levels of reactive oxygen species (ROS), and recurrent bacterial infections are key factors contributing to the development of chronic wounds from skin injuries.

[0004] With the continuous development of biomedical materials and the deepening research on wound healing theory, researchers have found that gel dressings, which can provide a moist environment for the wound, are considered ideal dressings for treating chronic wounds. The high water content of gel dressings keeps granulation tissue and epithelial tissue in a moist environment. Their soft texture and low interfacial tension give them good biocompatibility and non-irritation, and help reduce inflammatory responses in adjacent areas. Gel dressings are soft and elastic, do not adhere to new tissue after wound healing, are easy to remove, and do not cause any discomfort to the patient. Gel dressings can also lower the temperature of the skin wound, thereby reducing pain. Antibacterial gel dressings, especially those loaded with sustained-release antibacterial agents, are increasingly widely used in the medical field, but they still have certain limitations. For example, they have poor adhesion to wounds and are prone to falling off; they cannot sufficiently reduce the concentration of reactive oxygen species at the wound site; their antibacterial properties are insufficient, or some antibacterial components, although having strong antibacterial properties, still have certain cellular or tissue toxicity. Enhancing the antibacterial properties of gel dressings, reducing their cytotoxicity, decreasing the content of reactive oxygen species at the wound site, and addressing inflammation at the wound site are all directions for the development of dressings for treating chronic wounds. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a chronic ulcer wound repair gel, its preparation method, and its application. This invention addresses the difficulties in the care and treatment of chronic infected wounds by providing a chronic ulcer wound repair gel that has excellent biocompatibility, high water retention and moisturizing capacity, strong mechanical properties, good breathability, and low toxicity, thereby promoting the healing of chronic wounds.

[0006] To achieve the above objectives, the technical solution of the present invention is as follows:

[0007] In a first aspect, the present invention provides a chronic ulcer wound repair gel, comprising a bacterial cellulose hydrogel and a functional component compounded on the bacterial cellulose hydrogel;

[0008] The functional ingredient is a mixture of glycerol, a suspension stabilizer, β-glucan, epigallocatechin-3-gallate, ε-polylysine, and a photosensitizer.

[0009] A second aspect of the present invention provides a method for preparing the above-mentioned chronic ulcer wound repair gel, comprising:

[0010] Bacterial cellulose was added to water to obtain a bacterial cellulose microfiber suspension;

[0011] Glycerol, suspension stabilizer, β-glucan, epigallocatechin-3-gallate and ε-polylysine were dissolved in water to obtain a compound solution;

[0012] The bacterial cellulose microfiber suspension was mixed with the compound solution to obtain a bacterial cellulose-based gel.

[0013] A photosensitizer was added to the bacterial cellulose-based gel, and the mixture was stirred to obtain a chronic ulcer wound repair gel.

[0014] A third aspect of the present invention provides the application of the above-described chronic ulcer wound repair gel or the chronic ulcer wound repair gel prepared by the above-described method in the preparation of wound dressings.

[0015] A fourth aspect of the present invention provides a wound dressing comprising the above-described chronic ulcer wound repair gel or the chronic ulcer wound repair gel prepared by the above-described preparation method.

[0016] The beneficial effects of this invention are as follows:

[0017] This invention addresses the challenges in the care and treatment of chronic wounds by providing a chronic ulcer repair gel. Bacterial cellulose possesses excellent biocompatibility, high water-holding capacity, strong mechanical properties, good breathability, and low toxicity. Utilizing these advantages, a bacterial cellulose-based chronic ulcer repair gel is prepared by combining it with functional components to promote chronic wound healing. This gel contains a large amount of water, which can drain moisture into the wound to moisturize excessively dry areas. Simultaneously, it has liquid affinity, absorbing wound exudate and bidirectionally regulating the wound's moisture balance. Furthermore, the gel contains numerous hydroxyl groups, exhibiting high water retention and a cooling sensation to effectively relieve pain. The gel state of bacterial cellulose also reduces irritation to the wound and mucous membranes, decreasing the sensitivity of exposed nerves and alleviating pain. Additionally, the photosensitizer in the gel, when irradiated with near-infrared laser, can inhibit bacterial infection, while the active ingredients can inhibit the spread of inflammation and promote the healing of chronic ulcers through collagen deposition and angiogenesis. Attached Figure Description

[0018] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0019] Figure 1 The images show the morphological characteristics of the chronic ulcer repair gel prepared in Example 1 of this invention; where A is a visual inspection image and B is an electron micrograph.

[0020] Figure 2 The results of the fibroblast culture experiment of the chronic ulcer wound repair gel prepared in Example 1 of the present invention are shown; wherein, A is a picture of the chronic ulcer wound repair gel applied on 3M skin-like tape, and B is a scanning electron microscope image after co-culture.

[0021] Figure 3 The image shows the anti-inflammatory effect of the chronic ulcer repair gel prepared in Example 1 of this invention; where A, B, and C are the pathological results of skin damage repair under light microscopy on days 3, 7, and 15 of the control group, respectively, and D, E, and F are the pathological results of skin damage repair under light microscopy on days 3, 7, and 15 of the chronic ulcer repair gel group, respectively. Scale bar = 100 μm.

[0022] Figure 4 The image shows the antibacterial performance test results of the chronic ulcer repair gel prepared in Example 1 of the present invention; where A is the inhibition zone diagram against Escherichia coli and B is the inhibition zone diagram against Staphylococcus aureus.

[0023] Figure 5 The moisturizing properties of the chronic ulcer wound repair gel prepared in Example 1 of this invention;

[0024] Figure 6 The images show the physical products of the chronic ulcer repair gels prepared in Example 1(B) and Comparative Example 1(A) of this invention.

[0025] Figure 7 The moisturizing properties of the chronic ulcer wound repair gel prepared in Comparative Example 1 of this invention;

[0026] Figure 8 This invention compares the effects of the chronic ulcer repair gels prepared in Example 1, Comparative Example 3, Comparative Example 4, and Comparative Example 5 of the present invention on repairing chronic ulcer wounds.

[0027] Figure 9 Evaluation of the sustained-release performance of the chronic ulcer repair gel prepared in Example 1 of this invention. Detailed Implementation

[0028] In view of the difficulties in the care and treatment of existing chronic infected wounds (the presence of inflammatory cytokines at the wound site, excessive levels of reactive oxygen species (ROS), and repeated bacterial infections leading to the development of chronic wounds), this invention proposes a chronic ulcer wound repair gel, its preparation method, and its application.

[0029] A first typical embodiment of the present invention provides a chronic ulcer wound repair gel, comprising a bacterial cellulose hydrogel and a functional component compounded on the bacterial cellulose hydrogel;

[0030] The functional ingredient is a mixture of glycerol, a suspension stabilizer, β-glucan, epigallocatechin-3-gallate, ε-polylysine, and a photosensitizer.

[0031] The presence of inflammatory cytokines, excessive levels of reactive oxygen species (ROS), and repeated bacterial infections are key factors leading to the development of chronic wounds from skin damage. This invention addresses the challenges in the care and treatment of chronic wounds by providing a chronic ulcer repair gel. Due to the excellent biocompatibility, high water-holding capacity, strong mechanical properties, good breathability, and low toxicity of bacterial cellulose, this invention utilizes the material advantages of bacterial cellulose to synthesize functional components, thereby preparing a bacterial cellulose-based chronic ulcer repair gel (hereinafter referred to as BC composite gel) that promotes the healing of chronic wounds.

[0032] BC composite gel contains a large amount of water, which can drain moisture into the wound to moisturize excessively dry wounds. It also has liquid affinity, absorbing wound exudate and regulating the wound's moisture balance in both directions. Furthermore, BC composite gel contains a large number of hydroxyl groups, making it highly water-retaining and providing a cooling sensation, effectively relieving pain. The gel state of bacterial cellulose reduces irritation to the wound and mucous membranes, decreases the sensitivity of exposed nerves, and alleviates pain. In addition, the photosensitizer in BC composite gel, when irradiated with near-infrared laser, can inhibit bacterial infection, and the active ingredients can inhibit the spread of inflammation, promote collagen deposition and angiogenesis, thus promoting the healing of chronic ulcers.

[0033] In some embodiments of this implementation, the suspension stabilizer is carboxymethyl cellulose.

[0034] In some embodiments of this implementation, the molecular weight of the ε-polylysine is 3600-4300.

[0035] In some embodiments of this implementation, the photosensitizer is toluidine blue.

[0036] Specifically, the functions of each component in the chronic ulcer wound repair gel provided by this invention are as follows:

[0037] Bacterial cellulose (BC): This invention uses bacterial cellulose as a raw material to form bacterial cellulose microfibers. The slow-release rate of the gel components is controlled by adjusting the different lengths of the microfibers. Using bacterial cellulose microfibers as a raw material, bacterial cellulose itself contains a large amount of water, which can drain moisture to the wound surface, thus moisturizing excessively dry wounds. Simultaneously, it has liquid affinity, absorbing wound exudate and bidirectionally regulating the wound's moisture balance. Furthermore, the BC composite gel contains a large number of hydroxyl groups, exhibiting high water retention and a cooling sensation, effectively relieving pain. The gel state of the bacterial cellulose patch reduces irritation to the wound and mucous membranes, reduces the sensitivity of exposed nerves, and alleviates pain. Simultaneously, the microfibers can reassemble into a porous network structure within the gel, forming a film on the skin surface that provides breathability and bacterial barrier properties.

[0038] Glycerin: It has a gel-like moisturizing effect and forms a soft film that will not crack due to the opening and closing of skin texture.

[0039] Carboxymethyl cellulose: a thickener and suspension stabilizer. It allows bacterial cellulose microfibers to be uniformly suspended in the gel, thereby forming a stable porous network structure.

[0040] β-glucan (β1,3-glucan): Its unique biological functions and physicochemical properties (such as anticoagulation, antioxidant, cell proliferation promotion, antibacterial, and water-absorbing properties) can produce a variety of functions, including moisturizing, delaying aging, promoting the proliferation of epithelial fibroblasts, and beautifying skin tone. It can also promote wound healing and eliminate wound infections caused by Staphylococcus aureus.

[0041] Epigallocatechin-3-gallate (EGCG): It can regulate the balance between M1 macrophages (which promote inflammatory responses) and M2 macrophages (which promote collagen synthesis) in the wound area, thereby inhibiting the inflammatory response. Most chronic wounds are associated with the formation of bacterial biofilms, which are mainly composed of bacteria, polysaccharides, proteins, and lipids. These biofilms are tight, hydrated extracellular polymers that significantly enhance bacterial resistance to antibiotics and resistance to host immune defenses, and are a major cause of bacterial resistance. EGCG can inhibit bacterial biofilm formation by interfering with the assembly of amyloid fibers and the formation of phosphoethanolamine-modified cellulose fibrils.

[0042] ε-Polylysine: It is synthesized by microorganisms, with a molecular weight between 3600 and 4300. It is composed of more than 10 lysine monomers and has broad-spectrum antibacterial properties, inhibiting both Gram-positive and Gram-negative bacteria.

[0043] Toluidine blue (TB): TB is a thiazide cationic dye that has been proven to be an effective photosensitizer, capable of effectively killing many microorganisms and their virulence factors. However, because TB readily undergoes dimerization in solution to form aggregates, it leads to a decrease in the production and lifetime of reactive oxygen species (especially singlet states), thus reducing photosensitivity and affecting its application in photodynamic therapy (PDT). This invention adds TB to a gel formed from BC and carboxymethyl cellulose. Both BC and carboxymethyl cellulose can prevent TB from polymerizing, ensuring the content of TB monomers and generating more reactive oxygen species (ROS), thereby playing an anti-inflammatory, bactericidal, and antibacterial role, and promoting the healing of infected wounds.

[0044] A second typical embodiment of the present invention provides a method for preparing the above-mentioned chronic ulcer wound repair gel, comprising:

[0045] Bacterial cellulose was added to water to obtain a bacterial cellulose microfiber suspension;

[0046] Glycerol, suspension stabilizer, β-glucan, epigallocatechin-3-gallate and ε-polylysine were dissolved in water to obtain a compound solution;

[0047] The bacterial cellulose microfiber suspension was mixed with the compound solution to obtain a bacterial cellulose-based gel.

[0048] A photosensitizer was added to the bacterial cellulose-based gel, and the mixture was stirred to obtain a chronic ulcer wound repair gel.

[0049] This invention combines bacterial cellulose-based hydrogels with functional components using the above method. These functional components endow the gel with multiple functions, and the sustained release of these components within the gel is beneficial for maintaining a healthy wound healing environment.

[0050] In some embodiments of this implementation, the bacterial cellulose is added to the water in a mass ratio of 1:3-5, specifically 1:3, 1:4, 1:5, etc.

[0051] In some embodiments of this implementation, the compound solution contains 3-5 wt% glycerol, 0.5-2 wt% suspension stabilizer, 0.01-0.5 wt% β-glucan, 0.01-0.2 wt% epigallocatechin-3-gallate, and 0.1-5 wt% ε-polylysine.

[0052] It should be noted that during the preparation of the compound solution, all functional components need to be completely dissolved. The dissolution rate of the functional components can be increased under heating conditions, for example, they can be dissolved under a water bath at 55-65℃.

[0053] In some embodiments of this implementation, the volume ratio of the bacterial cellulose microfiber suspension to the compound solution is 5:5-8:2.

[0054] In some embodiments of this implementation, the preparation method includes: adding bacterial cellulose to water, mixing at a speed of 6000-10000 r / min for 15-30 min, ultrasonically homogenizing, and then processing with a colloid mill to obtain a bacterial cellulose microfiber suspension; preferably, the colloid mill parameters are such that the gap is gradually adjusted from 0.15 mm to 0.1 mm. Utilizing fluid dynamics for dispersion, ultrasonic homogenization, and colloid milling can reduce the size of bacterial cellulose, obtaining bacterial cellulose microfibers, and ensuring their full dispersion in water to obtain a suspension.

[0055] In some embodiments of this implementation, the suspension stabilizer is carboxymethyl cellulose. The addition of carboxymethyl cellulose allows the fine fibers in bacterial cellulose to be uniformly suspended in the gel, thereby forming a stable network porous structure and improving the air permeability of the gel.

[0056] In some embodiments of this implementation, the molecular weight of the ε-polylysine is 3600-4300. ε-polylysine with a molecular weight between 3600-4300 exhibits the best antibacterial activity.

[0057] In some embodiments of this implementation, the mixing is performed by high-pressure homogenization at a pressure of 1000-1800 bar and a temperature of 35-55°C.

[0058] In some embodiments of this implementation, the photosensitizer is toluidine blue, and the concentration of toluidine blue in the chronic ulcer wound repair gel is 0.5-5 μM, specifically 0.5 μM, 0.6 μM, 0.8 μM, 1 μM, 1.5 μM, 2 μM, 2.5 μM, 3 μM, 3.5 μM, 4 μM, 4.5 μM, 5 μM, etc.

[0059] It should be noted that toluidine blue is prone to dimerization in solution, forming aggregates that reduce photosensitivity. To prevent TB from polymerizing in solution, BC and carboxymethyl cellulose are added in the final step to inhibit TB polymerization and ensure the TB monomer content in the gel.

[0060] In some embodiments of this implementation, after the photosensitizer is added and stirred, air bubbles are introduced into the gel due to stirring. The presence of air bubbles affects the performance of the gel, such as viscosity, stickiness, and service life. Therefore, it is necessary to remove the air bubbles, which can be eliminated by negative pressure degassing.

[0061] A third typical embodiment of the present invention provides the application of the above-described chronic ulcer wound repair gel or the chronic ulcer wound repair gel prepared by the above-described method in the preparation of wound dressings.

[0062] In some embodiments of this implementation, the wound is a chronic skin ulcer.

[0063] A fourth typical embodiment of the present invention provides a wound dressing, comprising the above-described chronic ulcer wound repair gel or the chronic ulcer wound repair gel prepared by the above-described preparation method.

[0064] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0065] Unless otherwise specified, the raw materials used in the following examples are all conventional products that can be purchased.

[0066] Example 1

[0067] A method for preparing a chronic ulcer wound repair gel includes the following steps:

[0068] (1) Bacterial cellulose and deionized water were mixed at a mass ratio of 1:4 and dispersed using fluid dynamics at a speed of 8000 r / min for 25 min. The mixture was then homogenized by ultrasonication and processed by a colloid mill. The colloid mill parameters were adjusted from the gap of 0.15 mm to 0.1 mm to obtain a bacterial cellulose microfiber suspension.

[0069] (2) Mix 4g glycerol, 1.25g carboxymethyl cellulose, 0.25g β-glucan, 0.1g epigallocatechin-3-gallate, and 2.5g ε-polylysine, add water to 100g, and dissolve in a water bath at 60℃ to obtain a compound solution.

[0070] (3) The bacterial cellulose microfiber suspension obtained in step (1) is mixed with the compound solution obtained in step (2) and subjected to high pressure homogenization treatment at 1400 bar and 45°C to form a bacterial cellulose-based gel.

[0071] (4) Add 3 μM toluidine blue to the bacterial cellulose-based gel obtained in step (3), stir evenly, and degas under negative pressure to obtain bacterial cellulose-based chronic ulcer repair gel.

[0072] Performance characteristics:

[0073] (1) As Figure 1 As shown in Figure (A), the chronic ulcer wound repair gel obtained in Example 1 is a semi-transparent, amorphous gel. This facilitates observation of wound healing without repeatedly peeling the gel to check, thus avoiding secondary damage to the wound. Furthermore, it is convenient for packing wounds with subcutaneous tunnels or deeper injuries. The gel surface is moist, soft, and elastic, causing no discomfort to the patient. The morphology and microstructure of the chronic ulcer wound repair gel obtained in Example 1 were characterized using scanning electron microscopy (SEM). Figure 1 As shown in Figure (B), the internal structure of the chronic ulcer wound repair gel is loose and porous, which facilitates gas exchange. Its water vapor transmission rate was measured to be 2658.6 gm³. -2 twenty four -h It meets the relevant requirements for contact wound dressings. The internal structure contains numerous microspheres, enabling sustained release of substances and promoting the continuous maintenance of a healthy wound healing environment.

[0074] The gel system constructed by this invention is a matrix framework for sustained-release drugs, which can be combined with a variety of active substances and drugs. The active substances in the chronic ulcer repair gel prepared by this invention are β-glucan, epigallocatechin-3-gallate, ε-polylysine and TB. These active substances can be released in a sustained manner, which is conducive to the continuous maintenance of the wound healing environment.

[0075] Because the methods for detecting the sustained-release properties of active ingredients TB, β-glucan, epigallocatechin-3-gallate, and ε-polylysine are not yet mature, this embodiment uses cannabidiol (CBD) as a representative drug to analyze the sustained-release performance of the chronic ulcer wound repair gel. Cannabidiol (CBD) and toluidine blue were added simultaneously, and the sustained-release performance of the resulting chronic ulcer wound repair gel was evaluated. The follow-up detection results of cannabidiol (CBD) are as follows: Figure 9 As shown in the figure, the chronic ulcer wound repair gel provided by the present invention has excellent sustained-release properties.

[0076] (2) The chronic ulcer repair gel obtained in Example 1 can be used as a photosensitizer for photodynamic therapy. Toluidine blue has good selectivity for bacteria, can effectively penetrate tissue and distribute to infected target tissue, but does not damage normal tissue.

[0077] (3) The pH value of the chronic ulcer repair gel obtained in Example 1 was found to be 5.8. A slightly acidic environment can affect the growth and proliferation of pathogens. The optimal pH value for the growth and proliferation of most pathogens causing wound infections is 7.2-7.4. For example, the ideal pH value for the growth and proliferation of Staphylococcus aureus is 7.0-7.5, the ideal pH value for Pseudomonas aeruginosa is 6.6-7.0, and the ideal pH value for Enterococcus is 7.0-9.0. At lower pH values, the growth of these pathogens is inhibited. In addition, a slightly acidic microenvironment can promote wound healing.

[0078] (4) BC dressing and chronic ulcer repair gel were co-cultured with fibroblasts, and the cytotoxicity of the gel was evaluated by changes in cell proliferation. High-density polyethylene extract was used as the control, a material that does not produce cytotoxicity. As a negative control, all other media, processes, and methods were the same as in the experimental group. The results are shown in Table 1. The study found that the chronic ulcer repair gel obtained in Example 1 had low cytotoxicity and was safe and non-toxic to humans. Both the pure BC dressing and the chronic ulcer repair gel exhibited very low cytotoxicity. In contrast, the chronic ulcer repair gel had a higher relative cell proliferation rate and was less cytotoxic and safer.

[0079] Table 1. Relative cell proliferation rate (x±s, n=3)

[0080]

[0081] (5) Fibroblast culture assay

[0082] The chronic ulcer repair gel prepared in Example 1 was applied to 3M skin-like adhesive tape, and fibroblasts were then coated onto the tape for co-culture. Figure 2 As shown in (A), the growth of fibroblasts on the surface of chronic ulcer repair gel was observed by scanning electron microscopy.

[0083] The results are as follows Figure 2 As shown in (B), fibroblasts can grow extensively on the surface of the chronic ulcer wound repair gel, indicating that the chronic ulcer wound repair gel can promote wound healing and reduce scar formation.

[0084] (6) A skin defect was created on the back of diabetic rats. A small amount of mixed bacterial suspension was used to infect the skin defect, thus constructing a chronic ulcer model. The successfully modeled diabetic rats were randomly divided into an experimental group and a control group. The chronic ulcer repair gel prepared in Example 1 was applied to the surface of the chronic ulcers in the experimental group, while the chronic ulcers in the control group were left untreated. Skin repair was assessed under a light microscope on days 3, 7, and 15. Figure 3 As shown, histopathological examination revealed a significant inflammatory response in the blank control group on day 3, while the chronic ulcer wound repair gel group showed a significantly lower inflammatory response. On day 3, both groups showed obvious granulation tissue formation. The chronic ulcer wound repair gel group exhibited gland-like structures, while the control group showed significantly less epithelialization. By day 15, the control group consisted almost entirely of granulation tissue. In contrast, the chronic ulcer wound repair gel group closely resembled natural skin, with a thinner stratum corneum, a dermis filled with collagen, and a corresponding increase in glands.

[0085] The chronic ulcer repair gel obtained in Example 1 can bind to human receptors, reduce the secretion of inflammatory factors, control the migration of inflammatory cells, and promote the secretion of the human antimicrobial peptide β-defensin. It can inhibit skin inflammation and enhance skin immunity, and quickly relieve skin inflammation problems.

[0086] (7) Antibacterial properties

[0087] The inherent and durable antibacterial activity of wound dressings is crucial for preventing bacterial adhesion, inflammatory responses, and wound infection. The antibacterial properties of the chronic ulcer wound repair gel obtained in Example 1 were tested using Gram-negative *Escherichia coli* and Gram-positive *Staphylococcus aureus* as representative bacteria. Luria-Bertani (LB) solid medium was used for the test. First, the bacteria were passaged in a suitable medium to confirm their concentration. Then, suspensions containing *Escherichia coli* and *Staphylococcus aureus* were aliquoted and spread onto the surface of the solid medium for inoculation. The chronic ulcer wound repair gel was then placed at different locations on the medium and exposed to light at a wavelength of 630-660 nm and a dose of 10 J / cm². 2 Irradiation time: Near-infrared laser irradiation treatment for 0-5 minutes, followed by observation of the inhibition zone after 24 hours in a 37℃ constant temperature chamber.

[0088] Test results as follows Figure 4 As shown, the chronic ulcer wound repair gel has an inhibitory effect on both Escherichia coli and Staphylococcus aureus.

[0089] (8) Moisturizing properties

[0090] Good water retention properties of wound dressings are crucial for providing a long-lasting moist environment, dissolving necrotic tissue, preventing scab formation, and promoting wound healing. The chronic ulcer wound repair gel obtained in Example 1 was applied to 3M synthetic leather tape, which was then affixed to the outer wall of a container with a 37°C water circulation system. Simulating human body temperature, the weight of the chronic ulcer wound repair gel was removed and recorded at regular intervals, and its water loss rate was calculated.

[0091] The results are as follows Figure 5 As shown, the chronic ulcer wound repair gel obtained in Example 1 has excellent moisturizing properties, with a water loss rate of only 50% after 16 hours, and a long service life.

[0092] Example 2

[0093] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that: in step (1), the mass ratio of bacterial cellulose to deionized water is 1:3, and the remaining steps are the same as in Example 1.

[0094] Example 3

[0095] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that: in step (1), the mass ratio of bacterial cellulose to deionized water is 1:5, and the remaining steps are the same as in Example 1.

[0096] Example 4

[0097] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that: in step (2), 3g glycerol, 0.5g carboxymethyl cellulose, 0.01g β-glucan, 0.01g epigallocatechin-3-gallate, and 0.1g ε-polylysine are mixed and then water is added to 100g. The remaining steps are the same as in Example 1.

[0098] Example 5

[0099] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that: in step (2), 5g glycerol, 2g carboxymethyl cellulose, 0.5g β-glucan, 0.2g epigallocatechin-3-gallate, and 5g ε-polylysine are mixed and then water is added to 100g. The remaining steps are the same as in Example 1.

[0100] Example 6

[0101] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that: in step (4), 0.5 μM toluidine blue is added to the bacterial cellulose-based gel obtained in step (3), and the remaining steps are the same as in Example 1.

[0102] Example 7

[0103] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that: in step (4), 5 μM toluidine blue is added to the bacterial cellulose-based gel obtained in step (3), and the remaining steps are the same as in Example 1.

[0104] Testing revealed that the chronic ulcer repair gels obtained in Examples 2-7 exhibited similar performance to those obtained in Example 1, with both gels possessing a loose, porous internal structure and a water vapor permeability exceeding 2000 g / m. -2 twenty four -h It has a microsphere structure inside, which can release functional ingredients slowly. It has good moisturizing properties and can be used as a photosensitizer for photodynamic therapy. It has a pH value of 5-7, low cytotoxicity, is safe and non-toxic to the human body, can promote wound healing, relieve skin inflammation problems, and inhibit Escherichia coli and Staphylococcus aureus.

[0105] Comparative Example 1

[0106] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that carboxymethyl cellulose is not added in step (2). The remaining steps are the same as in Example 1.

[0107] Figure 6 Image (A) is a photograph of the gel obtained in Comparative Example 1. Figure 6 Image B is a photograph of the gel obtained in Example 1 of this invention. Figure 6 It is known that adding carboxymethyl cellulose can effectively prevent TB from undergoing a polymerization reaction. Furthermore, this invention has found that carboxymethyl cellulose is more effective than BC in preventing TB from polymerizing, and the two have a certain synergistic effect. TB polymerization affects the photodynamic therapy effect; therefore, the photodynamic therapy effect of the gel obtained in Comparative Example 1 is poor.

[0108] Comparative Example 2

[0109] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that: in step (2), no glycerin is added, while the remaining steps are the same as in Example 1.

[0110] Figure 7 The gel obtained in Comparative Example 2 exhibits poorer moisturizing properties than the gel obtained in Example 1, with a water loss rate of 50% after approximately 8 hours. This results in a shorter service life.

[0111] Comparative Example 3

[0112] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that: in step (2), β-glucan is not added, while the remaining steps are the same as in Example 1.

[0113] Comparative Example 4

[0114] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that epigallocatechin-3-gallate is not added in step (2), while the remaining steps are the same as in Example 1.

[0115] Comparative Example 5

[0116] A method for preparing a chronic ulcer wound repair gel differs from Example 1 in that: in step (2), ε-polylysine is not added, while the remaining steps are the same as in Example 1.

[0117] To evaluate the efficacy of the repair gel in repairing chronic ulcer wounds, small amounts of a mixed bacterial suspension were used to infect the wounds of diabetic rats. The wounds were then tested with different gel formulations, and the healing outcomes were observed. Figure 8 As shown. Comparative Example 3, without the addition of β-glucan, showed slower wound healing, less pronounced inflammatory response, and high wound cleanliness. Comparative Examples 4 and 5 exhibited bacterial infection and significant inflammatory response; although the wound area decreased after 15 days, the wounds remained deep with purulent exudate.

[0118] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A chronic ulcer wound repair gel, characterized in that, The functional ingredient is mixed by glycerol, suspension stabilizer, beta-glucan, epigallocatechin-3-gallate, epsilon-polylysine and photosensitizer. The preparation method of the chronic ulcer wound repair gel comprises the following steps: adding bacterial cellulose into water to obtain a bacterial cellulose micro-fiber suspension; dissolving glycerol, a suspension stabilizer, beta-glucan, epigallocatechin-3-gallate and epsilon-polylysine in water to obtain a compound solution; uniformly mixing the bacterial cellulose micro-fiber suspension and the compound solution to obtain a bacterial cellulose-based gel; adding a photosensitizer into the bacterial cellulose-based gel and stirring to obtain the chronic ulcer wound repair gel. The bacterial cellulose and water are mixed at a mass ratio of 1:3-5. In the compound solution, the concentration of glycerol is 3-5 wt%, the concentration of the suspension stabilizer is 0.5-2 wt%, the concentration of beta-glucan is 0.01-0.5 wt%, the concentration of epigallocatechin-3-gallate is 0.01-0.2 wt%, and the concentration of epsilon-polylysine is 0.1-5 wt%. The volume ratio of the bacterial cellulose micro-fiber suspension to the compound solution is 5:5-8:

2. The photosensitizer is toluidine blue, and the concentration of toluidine blue in the chronic ulcer wound repair gel is 0.5-5 μM. The suspension stabilizer is carboxymethyl cellulose.

2. The chronic ulcer wound repair gel of claim 1, wherein, The molecular weight of the epsilon-polylysine is 3600-4300.

3. The chronic ulcer wound repair gel of claim 1, wherein, The preparation method comprises the following steps: adding bacterial cellulose into water to obtain a bacterial cellulose micro-fiber suspension; dissolving glycerol, a suspension stabilizer, beta-glucan, epigallocatechin-3-gallate and epsilon-polylysine in water to obtain a compound solution; uniformly mixing the bacterial cellulose micro-fiber suspension and the compound solution to obtain a bacterial cellulose-based gel; adding a photosensitizer into the bacterial cellulose-based gel and stirring to obtain the chronic ulcer wound repair gel.

4. A process for the preparation of a chronic ulcer wound repair gel as claimed in claim 1, characterized in that, The bacterial cellulose and water are mixed at a mass ratio of 1:3-5. In the compound solution, the concentration of glycerol is 3-5 wt%, the concentration of the suspension stabilizer is 0.5-2 wt%, the concentration of beta-glucan is 0.01-0.5 wt%, the concentration of epigallocatechin-3-gallate is 0.01-0.2 wt%, and the concentration of epsilon-polylysine is 0.1-5 wt%. The volume ratio of the bacterial cellulose micro-fiber suspension to the compound solution is 5:5-8:

2. The photosensitizer is toluidine blue, and the concentration of toluidine blue in the chronic ulcer wound repair gel is 0.5-5 μM. The preparation method comprises the following steps: adding bacterial cellulose into water, mixing at a rotating speed of 6000-10000 r / min for 15-30 min, ultrasonic homogenizing, and treating by a colloid mill to obtain the bacterial cellulose micro-fiber suspension. The gap of the colloid mill is gradually adjusted from 0.15 mm to 0.1 mm. ​ ​ ​ 5. The production method according to claim 4, wherein ​ 6. The production method according to claim 5, wherein ​ 7. The production method according to claim 4, wherein The suspension stabilizer is carboxymethylcellulose.

8. The production method according to claim 4, wherein The molecular weight of the epsilon-polylysine is 3600-4300.

9. The production method according to claim 4, wherein The mixing is carried out by high pressure homogenization at a pressure of 1000-1800 bar and a temperature of 35-55°C.

10. Use of a chronic ulcer wound healing gel as defined in any one of claims 1 to 3 or prepared by the method of any one of claims 4 to 9 in the preparation of a wound dressing. The wound is a chronic skin ulcer.

11. A wound dressing, characterized in that, The wound is a chronic skin ulcer. The wound is a chronic skin ulcer.

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