Aqueous gel dressing with antibacterial and scar-preventing effects and preparation method thereof

Abstract

The invention belongs to the technical field of wound dressings, and discloses a hydrogel dressing with antibacterial and scar-preventing effects and a preparation method thereof.3-fluoro-4-carboxyphenylboronic acid grafted chitosan oligosaccharide is introduced, phenylboronic acid bonds are matched with a large number of catechol structures in a tannic acid solution to form dynamic boron ester bonds, and the dynamic boron ester bonds are grafted to the chitosan oligosaccharide; the preparation method comprises the following steps: carrying out joint response with supramolecular forces such as hydrogen bonds to form a network gel structure, enabling boron ester bonds to respond to a high ROS level of a wound microenvironment and an acidic environment caused by bacterial infection to break, so as to efficiently release cyclooxygenase-2 selective non-steroidal anti-inflammatory drug celecoxib, and enabling the vinipofen liposome to be limited by a relatively large volume, so that the vinipofen liposome has a good anti-inflammatory effect. The time of staying in the dressing is longer, and continuous and stable release can be maintained in the whole wound healing process range, so that the effects of on-demand inflammation regulation and control and long-acting mechanical response regulation and control are achieved.

Description

Technical Field

[0001] The present application belongs to the technical field of wound dressings, and specifically relates to an aqueous gel dressing with antibacterial and scar prevention effects and a preparation method thereof. Background Art

[0002] Scars are an abnormal healing condition commonly seen in burns, surgical wounds, or infections, characterized by persistent pain, itching, and cosmetic disfigurement. Pathologically, scars are characterized by abnormal proliferation of myofibroblasts and accumulation of extracellular matrix. Scars are invasive to surrounding normal skin tissue, do not regress spontaneously, and carry a risk of developing into scar cancer. Scars are uniquely human.

[0003] Current clinical treatment strategies for keloids include surgical excision, physical therapy such as cryosurgery and laser therapy, and the use of chemical agents such as 5-fluorouracil to inhibit scarring through myofibroblasts. However, according to clinical statistics, existing treatments are ineffective and have high recurrence rates. Furthermore, common treatments can significantly affect the normal cells surrounding the scar tissue, leading to significant waste of medical resources annually. Therefore, the development of novel, specific scar prevention and treatment strategies is crucial.

[0004] However, both the pathological research and treatment of scars have been slow to progress, as the pathogenesis of scars remains unclear. There are three possible explanations for the main causes: (1) Theory that during the inflammatory phase, inflammatory factors stimulate an increase in M1 macrophages and a large amount of inflammatory factors, leading to abnormal proliferation of myofibroblasts; (2) the epithelial-mesenchymal cell theory; and (3) the theory of abnormal myofibroblast signaling during the proliferative phase. In summary, the pathogenesis of scars is believed to be multifactorial and closely related to the wound healing stage of the human body.

[0005] Generally speaking, wound healing can be divided into four phases: (1) the coagulation phase; (2) the inflammatory phase of the wound caused by infection, which is characterized by increased ROS stress and bacterial proliferation; (3) the proliferation phase of myofibroblast differentiation and regulatory signal transduction; and (4) the remodeling phase of wound healing and repair and differentiation. According to mainstream theory, the inflammatory phase and the proliferation phase are often considered to be the main phases of scar development.

[0006] Current research on keloids primarily focuses on signaling regulation of myofibroblasts, inhibiting the activation of related pathways such as TGF-β1, SMAD, MAPK, and Wnt. However, most studies focus on a specific phase of wound remodeling, ignoring the continuity of wound healing stages and the close connections between them. Furthermore, the pathways targeted are often downstream of myofibroblasts and may also be abnormally expressed in a variety of other common diseases.

[0007] Recent studies have shown that the mechanotransduction signaling protein YAP is closely associated with skin scarring and scar formation. By inhibiting the YAP-TEAD interaction, YAP is prevented from activating negative En1 myofibroblasts (ENFs) to positive En1 myofibroblasts (EPFs). The former is responsible for normal tissue regeneration and repair, while the latter has been shown to be associated with scar formation in mice. Therefore, effectively blocking the YAP pathway to activate En1 is expected to inhibit scar formation while not affecting the tissue repair function of normal myofibroblasts.

[0008] Verteporfin is a commonly used photosensitizer, often used in phototherapy for tumors. It also induces apoptosis and inhibits autophagy. Recent studies have shown that verteporfin not only effectively blocks the YAP / TEAD pathway but also increases VEGF expression, promoting angiogenesis. It is used to treat retinal diseases such as age-related macular degeneration, which can also have a positive impact on wound healing. However, verteporfin has certain cytotoxic properties, making it difficult to use as a wound treatment agent.

[0009] Inspired by the scarless wound healing of fetuses, it is necessary to ensure the proliferation and differentiation capacity of cells at the affected area and relatively moist external conditions. Therefore, wound dressings need to have excellent water absorption and moisture retention to maintain a relatively moist environment on the wound surface and have a good bactericidal effect, thereby inhibiting the abnormal proliferation of scars and myofibroblasts. Hydrogel water-based dressings based on natural polymers can well meet the above conditions. The release rate of drugs depends on the size of drug molecules and pore size. The diameter of free drugs is only a few nanometers or even smaller, while the size of unilamellar liposomes is between 100-1000nm. Inspired by size exclusion chromatography and chromatographic separation methods, the release rate of impurities in hydrogels can be sorted in a volume-dependent manner, that is, the larger the particles, the slower the release rate.

[0010] Natural polymer hydrogels such as gelatin, hyaluronic acid, and chitosan offer advantages such as high water content, breathability, excellent moisture retention, easy degradation, and excellent biocompatibility. In particular, chitosan, with its high amino group content, can chemically bond with proteins on the cell membrane surface, achieving excellent adhesion. However, traditional chitosan is highly deacetylated and is only soluble in weak acids.

[0011] Therefore, there is great market prospect for developing a wound dressing that is antibacterial, fast-healing and prevents scar formation for infected wounds. Summary of the Invention

[0012] The purpose of this application is to solve the problems of the prior art and to provide an aqueous gel dressing with antibacterial and scar prevention effects and a preparation method thereof.

[0013] In order to solve the technical problem, the technical solution of the present application is: an aqueous gel dressing with antibacterial and scar prevention effects, comprising the following components: Phenylboronic acid grafted chitosan oligosaccharide, tannic acid, celecoxib, verteporfin liposomes and deionized water, according to weight percentage: phenylboronic acid grafted chitosan oligosaccharide 5-10%, tannic acid 5-10%, celecoxib 1-1.5%, verteporfin liposomes 0.01-0.03%, deionized water makes up the balance; The phenylboronic acid grafted chitosan oligosaccharide is prepared from chitosan oligosaccharide and 3-fluoro-4-carboxyphenylboronic acid, and the weight ratio of chitosan oligosaccharide to 3-fluoro-4-carboxyphenylboronic acid is 20:4-6; The verteporfin liposomes are made of a liposome lipid material and verteporfin, and the weight ratio of the liposome lipid material to verteporfin is 22-25:2.

[0014] Preferably, the preparation method of the phenylboronic acid grafted chitosan oligosaccharide is specifically as follows: At 4°C, 3-fluoro-4-carboxyphenylboronic acid is dispersed in a buffer solution with a pH of 5.5 to 6.5, and N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added. The mixture is stirred for 1 to 4 hours to activate the carboxyl group, thereby obtaining an activated mixed solution. Chitosan oligosaccharide was then added dropwise to the activated mixture, maintained at room temperature at 25°C, and stirred continuously for 12 to 32 hours. The mixture was then placed in a 1000 kDa dialysis bag and dialyzed against deionized water for 72 hours, followed by freeze-drying to obtain phenylboronic acid-grafted chitosan oligosaccharide; chitosan oligosaccharide: 3-fluoro-4-carboxyphenylboronic acid: N-hydroxysuccinimide: 1-ethyl-(3-dimethylaminopropyl)carbodiimide: buffer solution = 2 g: 0.47 g: 0.3 g: 0.5 g: 100 mL.

[0015] Preferably, the buffer solution is selected from 2-(N-morpholino)ethanesulfonic acid solution, dimethyl sulfoxide solution or phosphate solution.

[0016] Preferably, the liposome lipid material is selected from one or more of hydrogenated soybean lecithin, phospholipid-polyethylene glycol 2000, and cholesterol.

[0017] Preferably, the preparation method of the verteporfin liposomes is specifically as follows: Hydrogenated soybean lecithin, phospholipid-polyethylene glycol 2000, cholesterol, and verteporfin were placed in the same round-bottom flask and fully dissolved with chloroform. The liposome membrane was obtained by vacuum distillation at 37°C using a rotary evaporator. The liposome membrane was resuspended in ultrapure water and sonicated using a cell disruptor to obtain verteporfin liposomes. The ratio of hydrogenated soybean lecithin: phospholipid-polyethylene glycol 2000: cholesterol: verteporfin: chloroform: ultrapure water was 21 mg: 1 mg: 0-3 mg: 2 mg: 6 mL: 6 mL.

[0018] Preferably, the ultrasonic power and time of the cell disruptor are: 120-210 W, 6-12 min, working 5 s, resting 5 s.

[0019] Preferably, a method for preparing an aqueous gel dressing having antibacterial and scar prevention effects comprises the following steps: Step 1: preparing an aqueous solution of phenylboronic acid grafted chitosan oligosaccharide, an aqueous solution of celecoxib, an aqueous solution of tannic acid adjusted to pH 8 by sodium hydroxide, and an aqueous solution of verteporfin liposomes; Step 2: uniformly mixing the phenylboronic acid grafted chitosan oligosaccharide aqueous solution and the celecoxib aqueous solution to obtain a mixed solution A; Step 3: uniformly mixing the tannic acid aqueous solution and the verteporfin liposome aqueous solution to obtain a mixed solution B; Step 4: Mix mixed solution A and mixed solution B in a volume ratio of 1:1; Step 5: The final mixture is thoroughly mixed and poured into a syringe, and allowed to stand to obtain an aqueous gel dressing, which contains, by weight percentage: 5-10% phenylboronic acid grafted chitosan oligosaccharide, 5-10% tannic acid, 1-1.5% celecoxib, and 0.01-0.03% verteporfin liposomes.

[0020] Preferably, the mixed solution A and the mixed solution B are mixed evenly, and left at room temperature of 25° C. for 2 to 3 minutes to obtain an aqueous gel dressing.

[0021] Preferably, the preparation method of the celecoxib aqueous solution is: dissolving celecoxib in a small amount of dimethyl sulfoxide, and then mixing with deionized water, celecoxib: dimethyl sulfoxide: deionized water = 0.2 g: 2 mL: 8 mL.

[0022] Compared with the prior art, the advantages of this application are: (1) The present application discloses an aqueous gel dressing with antibacterial and scar prevention effects, which is achieved by introducing 3-fluoro-4-carboxylphenylboronic acid grafted chitosan oligosaccharides, wherein the phenylboronic acid bond cooperates with a large amount of catechol structures in the tannic acid solution to form a dynamic boron ester bond, which responds to supramolecular forces such as hydrogen bonds to form a network gel structure, wherein the boron ester bond can respond to the high ROS level in the wound microenvironment and the acidic environment caused by bacterial infection to break, thereby efficiently releasing the cyclooxygenase-2 selective non-steroidal anti-inflammatory drug celecoxib. Since the verteporfin liposomes are limited by their large size and stay in the dressing for a longer time, they can maintain continuous and stable release throughout the entire wound healing process, thereby achieving the effects of on-demand inflammation regulation and long-term mechanical response regulation. (2) The dressing of the present application has the characteristics of sequential release, synergistic immune regulation and cell mechanical response regulation. Compared with traditional single or non-regulatory wound dressings, the present application can not only promote wound healing but also prevent scarring; (3) The present application encapsulates verteporfin in liposomes, which can protect verteporfin on the one hand, and the larger particle size can greatly slow down its release rate, and on the other hand, it can reduce the photosensitivity effect of verteporfin and thus reduce cell phototoxicity; (4) The dressing preparation method of the present application adopts a chemical cross-linking method through dynamic boron ester bonds, which has the characteristics of responding to changes in the wound microenvironment. The hydrogel prepared by cross-linking has good physical and chemical properties. The modification method of the dressing raw materials is simple, and it can be prepared and expanded by itself. It is cheap, safe and reliable. (5) The dressing prepared by the preparation method of the present application has good biological properties, controllable degradation, and excellent cell compatibility. It also has good antibacterial, anti-inflammatory and ROS scavenging capabilities, and is used to promote scar-free wound regeneration; (6) The dressing obtained by the preparation method of the aqueous gel dressing with antibacterial and scar prevention effects of the present application has excellent injectability, can conform to wound surfaces of different rules, has a short gelling time, high stability, little irritation to the wound, and has good biocompatibility and biodegradability. At the same time, the dressing can effectively fight bacterial infection and promote scar-free healing of wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is an optical photograph scanned by a scanning electron microscope (SEM) of Example 6 of the present application; Figure 2 This is an optical photograph of the aqueous gel dressing of Example 6 of the present application; Figure 3 These are optical photographs of the supernatants from the hemolytic experiments of Examples 3 to 6 of the present application; Figure 4 This is a bar graph of the relative healing areas of Examples 5-6 of the present application, Comparative Example 1, and commercially available products M3 and M4 on rat wounds at 14 days of wound healing. DETAILED DESCRIPTION

[0024] The present application is described in detail below with reference to the accompanying drawings and specific examples, but the present application is not limited to these examples. This application covers any substitutions, modifications, equivalent methods, and solutions made within the spirit and scope of this application. To provide a thorough understanding of this application, specific details are described in detail in the following examples of this application, but those skilled in the art can fully understand this application without these detailed descriptions.

[0025] Natural polyphenols are compounds extracted from plants. They have been increasingly studied in recent years due to their excellent antibacterial, antioxidant, anti-inflammatory, bactericidal, and anti-aging properties. Their chemical structures are characterized by the presence of catechol groups in the ortho or para positions. Tannic acid, for example, has a hyperbranched structure with multiple catechol structures.

[0026] Hydrogels prepared from low-molecular-weight compounds typically have poor mechanical properties, are soft, and easily break under applied stress, making them difficult to use in applications requiring high mechanical strength, such as bone fillers and energy storage batteries. However, hydrogels with excellent plasticity are ideal for filling irregular skin wounds in pioneering wound prevention and treatment, achieving perfect coverage, isolating them from external bacteria, sequentially releasing drugs, and maintaining a moist environment and oxygen exchange.

[0027] Compared to chitosan, chitosan oligosaccharides possess higher biocompatibility and water solubility. Phenylboronic acid-modified chitosan oligosaccharides were prepared by reacting chitosan oligosaccharides with 3-fluoro-4-carboxyphenylboronic acid to modulate the chemical properties of chitosan oligosaccharides and reduce their positive charge. The fluorine element maintains the excellent hydrophilicity of the modified compound. Crucially, the introduction of 3-fluoro-4-carboxyphenylboronic acid results in the grafting of numerous phenylboronic acid bonds on the side chains of the compound. These bonds can then be chemically cross-linked in situ with the numerous catechol structures in tannic acid to form dynamic borylester bonds, which stabilize the three-dimensional structure of the hydrogel through supramolecular forces such as hydrogen bonding. Borylester bonds are unstable chemical bonds that are sensitive to pH and ROS, responsive to high acidity or reactive oxygen species (ROS) levels and cleavage. Therefore, this wound dressing not only meets the design requirements of irregular wound surfaces and injectability but also offers high design flexibility and programmable control to respond to changes in the wound microenvironment, enabling on-demand drug release.

[0028] The present application uses chitosan oligosaccharide, which has a small molecular weight and can be completely dissolved in water. It has a large functional effect and high biological activity and can be more effectively utilized by the human body. Its effect is about fourteen times that of traditional chitosan.

[0029] The matrix materials of the excipients in this application are all FDA-approved or natural compounds with good biocompatibility and affinity. The chitosan oligosaccharide side chain amino groups have good bioadhesion properties, and both chitosan oligosaccharide and tannic acid have antioxidant and antibacterial properties. Compared with traditional single-function wound dressings, this application integrates multiple functions such as adhesion, self-healing, anti-inflammatory, and antibacterial, providing a more comprehensive therapeutic effect.

[0030] The present application discloses an aqueous gel dressing with antibacterial and scar prevention effects, comprising the following components: Phenylboronic acid grafted chitosan oligosaccharide (PBA-COS), tannic acid (TA), celecoxib (CL), liposome verteporfin (L-VP) and deionized water, calculated by weight percentage: phenylboronic acid grafted chitosan oligosaccharide 5-10%, tannic acid 5-10%, celecoxib 1-1.5%, liposome verteporfin 0.01-0.03%, and deionized water makes up the balance; The phenylboronic acid grafted chitosan oligosaccharide is prepared from chitosan oligosaccharide and 3-fluoro-4-carboxyphenylboronic acid, and the weight ratio of chitosan oligosaccharide to 3-fluoro-4-carboxyphenylboronic acid is 20:4-6; The verteporfin liposomes are made of a liposome lipid material and verteporfin, and the weight ratio of the liposome lipid material to verteporfin is 22-25:2.

[0031] Preferably, the preparation method of the phenylboronic acid grafted chitosan oligosaccharide is specifically as follows: At 4°C, 3-fluoro-4-carboxyphenylboronic acid is dispersed in a buffer solution with a pH of 5.5 to 6.5, and N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added. The mixture is stirred for 1 to 4 hours to activate the carboxyl group, thereby obtaining an activated mixed solution. Chitosan oligosaccharide was then added dropwise to the activated mixture, maintained at room temperature at 25°C, and stirred continuously for 12 to 32 hours. The mixture was then placed in a 1000 kDa dialysis bag and dialyzed against deionized water for 72 hours, followed by freeze-drying to obtain phenylboronic acid-grafted chitosan oligosaccharide; chitosan oligosaccharide: 3-fluoro-4-carboxyphenylboronic acid: N-hydroxysuccinimide: 1-ethyl-(3-dimethylaminopropyl)carbodiimide: buffer solution = 2 g: 0.47 g: 0.3 g: 0.5 g: 100 mL.

[0032] pH can be 6.5, 6.2, 6.0, 5.8, 5.5; The stirring time of the first step can be 1h, 2h, 3h, 4h, etc.; The stirring time of the second step can be 12h, 16h, 20h, 24h, 28h, 32h, etc. Preferably, the buffer solution is selected from 2-(N-morpholino)ethanesulfonic acid solution, dimethyl sulfoxide solution or phosphate solution.

[0033] Preferably, the liposome lipid material is selected from one or more of hydrogenated soybean lecithin, phospholipid-polyethylene glycol 2000, and cholesterol.

[0034] Preferably, the preparation method of the verteporfin liposomes is specifically as follows: Hydrogenated soybean lecithin, phospholipid-polyethylene glycol 2000, cholesterol, and verteporfin were placed in the same round-bottom flask and fully dissolved with chloroform. The liposome membrane was obtained by vacuum distillation at 37°C using a rotary evaporator. The liposome membrane was resuspended in ultrapure water and sonicated using a cell disruptor to obtain verteporfin liposomes. The ratio of hydrogenated soybean lecithin: phospholipid-polyethylene glycol 2000: cholesterol: verteporfin: chloroform: ultrapure water was 21 mg: 1 mg: 0-3 mg: 2 mg: 6 mL: 6 mL.

[0035] The content ratio of hydrogenated soybean lecithin: lecithin-polyethylene glycol 2000: cholesterol: verteporfin: chloroform: ultrapure water can be: 21mg:1mg:0mg:2mg:6mL:6mL; 21mg:1mg:1mg:2mg:6mL:6mL; 21mg:1mg:2mg:2mg:6mL:6mL; 21mg:1mg:3mg:2mg:6mL:6mL, etc.

[0036] Preferably, the ultrasonic power and time of the cell disruptor are: 120-210 W, 6-12 min, working 5 s, resting 5 s.

[0037] Ultrasonication time can be 6min, 8min, 10min, 12min, etc.; The ultrasonic power can be 120W, 150W, 180W, 210W, etc.

[0038] By integrating verteporfin into the liposome lipid material, not only is the damage to the wound caused by the photosensitivity of verteporfin effectively prevented, but its larger size can also effectively avoid rapid release when the dressing is used, thereby enhancing the stability of drug release.

[0039] Preferably, a method for preparing an aqueous gel dressing having antibacterial and scar prevention effects comprises the following steps: Step 1: preparing an aqueous solution of phenylboronic acid grafted chitosan oligosaccharide, an aqueous solution of celecoxib, an aqueous solution of tannic acid adjusted to pH 8 by sodium hydroxide, and an aqueous solution of verteporfin liposomes; Step 2: uniformly mixing the phenylboronic acid grafted chitosan oligosaccharide aqueous solution and the celecoxib aqueous solution to obtain a mixed solution A; Step 3: uniformly mixing the tannic acid aqueous solution and the verteporfin liposome aqueous solution to obtain a mixed solution B; Step 4: Mix mixed solution A and mixed solution B in a volume ratio of 1:1; Step 5: The final mixture is thoroughly mixed and poured into a syringe, and allowed to stand to obtain an aqueous gel dressing, which contains, by weight percentage: 5-10% phenylboronic acid grafted chitosan oligosaccharide, 5-10% tannic acid, 1-1.5% celecoxib, and 0.01-0.03% verteporfin liposomes.

[0040] Preferably, the mixed solution A and the mixed solution B are mixed evenly, and left at room temperature of 25° C. for 2 to 3 minutes to obtain an aqueous gel dressing.

[0041] Preferably, the preparation method of the celecoxib aqueous solution is: dissolving celecoxib in a small amount of dimethyl sulfoxide, and then mixing with deionized water, celecoxib: dimethyl sulfoxide: deionized water = 0.2 g: 2 mL: 8 mL.

[0042] Example 1 1. Prepare PBA-COS solution, referred to as solution A.

[0043] 2. Prepare TA solution and adjust the pH to 8 with NaOH, which is referred to as solution B.

[0044] 3. Mix the above solution A and solution B in a ratio of 1:1 to obtain a mixed solution C.

[0045] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain a dressing sample. The dressing contains 5% phenylboronic acid-grafted chitosan oligosaccharide and 5% tannic acid.

[0046] Example 2 1. Prepare PBA-COS solution, referred to as solution A.

[0047] 2. Prepare TA solution and adjust the pH to 8 with NaOH, which is referred to as solution B.

[0048] 3. Mix the above solution A and solution B in a ratio of 1:2 to obtain a mixed solution C.

[0049] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain a dressing sample. The dressing contains 5% phenylboronic acid-grafted chitosan oligosaccharide and 10% tannic acid.

[0050] Example 3 1. Prepare PBA-COS solution, referred to as solution A.

[0051] 2. Prepare TA solution and adjust the pH to 8 with NaOH, which is referred to as solution B.

[0052] 3. Mix the above solution A and solution B in a ratio of 2:1 to obtain a mixed solution C.

[0053] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain a dressing sample. The dressing contains 10% phenylboronic acid-grafted chitosan oligosaccharide and 5% tannic acid according to weight percentage.

[0054] Example 4 1. Prepare a PBA-COS solution containing 20 mg / mL of CL, designated as solution A.

[0055] 2. Prepare TA solution and adjust the pH to 8 with NaOH, which is referred to as solution B.

[0056] 3. Mix the above solution A and solution B in a ratio of 1:1 to obtain a mixed solution C.

[0057] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain a dressing sample. The dressing contains 5% phenylboronic acid-grafted chitosan oligosaccharide, 5% tannic acid, and 1% celecoxib.

[0058] Example 5 1. Prepare PBA-COS solution, referred to as solution A.

[0059] 2. Prepare TA solution containing L-VP and adjust the pH to 8 with NaOH. This is referred to as solution B.

[0060] 3. Mix the above solution A and solution B in a ratio of 1:1 to obtain a mixed solution C.

[0061] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain a dressing sample. The dressing contains 10% phenylboronic acid-grafted chitosan oligosaccharide, 10% tannic acid, and 0.01% verteporfin liposomes.

[0062] Example 6 1. Prepare a PBA-COS solution containing CL, referred to as solution A.

[0063] 2. Prepare TA solution containing L-VP and adjust the pH to 8 with NaOH. This is referred to as solution B.

[0064] 3. Mix the above solution A and solution B in a ratio of 1:1 to obtain a mixed solution C.

[0065] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain a dressing sample. The dressing contains 10% phenylboronic acid-grafted chitosan oligosaccharide, 10% tannic acid, 1.5% celecoxib, and 0.03% verteporfin liposomes.

[0066] Comparative Example 1 1. Prepare phosphate buffered saline (PBS) at pH 7.4.

[0067] like Figure 1 As shown, this is the SEM scanning optical photograph of Example 6 of the present application, in which a three-dimensional network pore structure can be clearly observed. The network structure is dense and the pore size is uniform.

[0068] like Figure 2 Shown is an optical photograph of the gel formation of the hydrogel prepared in Example 6 of the present application.

[0069] like Figure 3 As shown, these are optical photographs of the supernatants from the hemolysis experiments of Examples 4 to 6 of the present application. None of the components of the present dressing causes significant hemosolubility, demonstrating the excellent biocompatibility of the dressing.

[0070] like Figure 4 As shown, it is a bar graph of the relative healing area of ​​Examples 5-6 of the present application, Comparative Example 1, and commercially available products M3 and M4 on the wound surface of rats at 14 days of wound healing, wherein Control represents Comparative Example 1, M3 represents the commercially available Chlorhexidine gel dressing, M4 represents the commercially available Buchmann gel dressing, M5 represents Example 5, and M6 represents Example 6.

[0071] As can be seen from the figure, the wound healing effects of Examples 5 to 6 of the present application are significantly better than those of Comparative Example 1, and are also significantly better than commercially available products.

[0072] The preferred embodiments of the present application have been described in detail above, but the present application is not limited to the above embodiments. Various changes can be made within the scope of knowledge possessed by ordinary technicians in this field without departing from the purpose of the present application.

[0073] Many other changes and modifications can be made without departing from the concept and scope of the present application. It should be understood that the present application is not limited to the specific embodiments, and the scope of the present application is defined by the appended claims.

Claims

1. A hydrogel dressing with antibacterial and scar prevention effects, characterized in that: Includes the following components: Phenylboronic acid grafted chitosan oligosaccharide, tannic acid, celecoxib, verteporfin liposomes and deionized water, according to weight percentage: phenylboronic acid grafted chitosan oligosaccharide 5-10%, tannic acid 5-10%, celecoxib 1-1.5%, verteporfin liposomes 0.01-0.03%, deionized water makes up the balance; The phenylboronic acid grafted chitosan oligosaccharide is prepared from chitosan oligosaccharide and 3-fluoro-4-carboxyphenylboronic acid, and the weight ratio of chitosan oligosaccharide to 3-fluoro-4-carboxyphenylboronic acid is 20:4-6; The verteporfin liposomes are made of a liposome lipid material and verteporfin, and the weight ratio of the liposome lipid material to verteporfin is 22-25:

2.

2. The aqueous gel dressing with antibacterial and scar prevention effects according to claim 1, characterized in that: The preparation method of the phenylboronic acid grafted chitosan oligosaccharide is specifically as follows: At 4°C, 3-fluoro-4-carboxyphenylboronic acid is dispersed in a buffer solution with a pH of 5.5 to 6.5, and N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide are added. The mixture is stirred for 1 to 4 hours to activate the carboxyl group, thereby obtaining an activated mixed solution. Then, chitosan oligosaccharide was added dropwise to the activated mixture, maintained at room temperature of 25°C, and stirred for 12 to 32 hours. The mixture was then placed in a dialysis bag and dialyzed against deionized water for 72 hours, and freeze-dried to obtain phenylboronic acid-grafted chitosan oligosaccharide; chitosan oligosaccharide: 3-fluoro-4-carboxyphenylboronic acid: N-hydroxysuccinimide: 1-ethyl-(3-dimethylaminopropyl)carbodiimide: buffer solution = 2 g: 0.47 g: 0.3 g: 0.5 g: 100 mL.

3. The aqueous gel dressing with antibacterial and scar prevention effects according to claim 2, characterized in that: The buffer solution is selected from 2-(N-morpholino)ethanesulfonic acid solution, dimethyl sulfoxide solution or phosphate solution.

4. The aqueous gel dressing with antibacterial and scar prevention effects according to claim 1, characterized in that: The liposome lipid material is selected from one or more of hydrogenated soybean lecithin, phospholipid-polyethylene glycol 2000 or cholesterol.

5. The aqueous gel dressing with antibacterial and scar prevention effects according to claim 4, characterized in that: The preparation method of the verteporfin liposome is specifically as follows: Hydrogenated soybean lecithin, phospholipid-polyethylene glycol 2000, cholesterol, and verteporfin were placed in the same round-bottom flask and fully dissolved with chloroform. The liposome membrane was obtained by vacuum distillation at 37°C using a rotary evaporator. The liposome membrane was resuspended in ultrapure water and sonicated using a cell disruptor to obtain verteporfin liposomes. The ratio of hydrogenated soybean lecithin: phospholipid-polyethylene glycol 2000: cholesterol: verteporfin: chloroform: ultrapure water was 21 mg: 1 mg: 0-3 mg: 2 mg: 6 mL: 6 mL.

6. The aqueous gel dressing with antibacterial and scar prevention effects according to claim 5, characterized in that: The ultrasonic power and time of the cell disruptor are: 120-210 W, 6-12 min, 5 s on, 5 s off.

7. A method for preparing an aqueous gel dressing with antibacterial and scar prevention effects, characterized in that: The following steps are involved: Step 1: preparing an aqueous solution of phenylboronic acid grafted chitosan oligosaccharide, an aqueous solution of celecoxib, an aqueous solution of tannic acid adjusted to pH 8 by sodium hydroxide, and an aqueous solution of verteporfin liposomes; Step 2: uniformly mixing the phenylboronic acid grafted chitosan oligosaccharide aqueous solution and the celecoxib aqueous solution to obtain a mixed solution A; Step 3: uniformly mixing the tannic acid aqueous solution and the verteporfin liposome aqueous solution to obtain a mixed solution B; Step 4: Mix mixed solution A and mixed solution B in a volume ratio of 1:1; Step 5: The final mixture is thoroughly mixed and poured into a syringe, and allowed to stand to obtain an aqueous gel dressing. The aqueous gel dressing contains the following weight percentages: 5-10% phenylboronic acid grafted chitosan oligosaccharide, 5-10% tannic acid, 1-1.5% celecoxib, and 0.01-0.03% verteporfin liposomes.

8. The method for preparing a water-based gel dressing with antibacterial and scar prevention effects according to claim 7, characterized in that: Mix the mixed solution A and the mixed solution B evenly, and place them at room temperature of 25°C for 2 to 3 minutes to obtain an aqueous gel dressing.

9. The method for preparing the aqueous gel dressing with antibacterial and scar prevention effects according to claim 7, characterized in that: The preparation method of the celecoxib aqueous solution is as follows: dissolving celecoxib in a small amount of dimethyl sulfoxide, and then mixing with deionized water, celecoxib: dimethyl sulfoxide: deionized water = 0.2 g: 2 mL: 8 mL.

Images