An aqueous gel dressing with antibacterial and preventive scar effect and a method of preparation

Abstract

The application belongs to the technical field of wound dressings, and discloses a water-based gel dressing with antibacterial and scar prevention effects and a preparation method, wherein 3-fluoro-4-carboxyphenylboronic acid is introduced to graft chitooligosaccharide, a large number of catechol structures in tannic acid solution are combined with the phenylboronic acid bond to form a dynamic boron ester bond, and a network gel structure is formed by responding to the supermolecular forces such as hydrogen bonds, wherein the boron ester bond can be broken in response to the high ROS level of the wound microenvironment and the acidic environment caused by bacterial infection, so as to efficiently release celecoxib, a selective non-steroidal anti-inflammatory drug of cyclooxygenase-2, and the liposome of verteporfin is limited in volume and stays in the dressing for a longer time, so that the sustained and stable release can be maintained in the whole wound healing process, thereby achieving the effects of on-demand inflammation regulation and long-acting mechanical response regulation.

Description

Technical Field

[0001] This application belongs to the field of wound dressing technology, specifically relating to an aqueous gel dressing with antibacterial and scar prevention effects and its preparation method. Background Technology

[0002] Scars are an abnormal healing condition commonly caused by burns, surgical wounds, or infections, characterized by persistent pain, itching, and cosmetic deformities. Pathologically, they are characterized by abnormal proliferation of myofibroblasts and excessive accumulation of extracellular matrix, exhibiting invasiveness towards surrounding normal skin tissue. They do not resolve spontaneously and carry a certain risk of developing into scar cancer, making them a uniquely human disease.

[0003] Current clinical strategies for treating keloids include surgical excision, cryotherapy, laser therapy, and other physical treatments, as well as the use of chemical agents such as 5-fluorouracil to inhibit scarring through myofibroblasts. However, according to clinical statistics, existing treatments have poor efficacy and high recurrence rates. Furthermore, common treatment strategies often have adverse effects on surrounding normal cells, resulting in a significant waste of medical resources annually. Therefore, researching specific and novel scar prevention and treatment strategies is essential.

[0004] However, progress in both pathological research and treatment of scars has been slow, due to the fact that the pathogenesis of scars remains unclear. There are three main possible explanations for the underlying causes: (1) the theory that during the inflammatory phase, stimulation by inflammatory factors leads to an increase in M1 macrophages and the production of large amounts of inflammatory factors, resulting in abnormal proliferation of myofibroblasts; (2) the epithelial-mesenchymal cell theory; and (3) the theory of abnormal signaling in myofibroblasts during the proliferative phase. In conclusion, the pathogenesis of scars is considered to be multifactorial and closely related to the wound healing stage in the human body.

[0005] Generally speaking, wound healing can be divided into four stages: (1) the coagulation stage; (2) the wound inflammation stage caused by infection, characterized by increased ROS stress and bacterial proliferation; (3) the proliferative stage of myofibroblast differentiation and regulation of signal transduction; and (4) the remodeling stage of basic wound healing and repair and differentiation. According to mainstream theory, the inflammation stage and the proliferative stage are often considered to be the main stages of scar formation.

[0006] Current research on keloids mainly focuses on signal regulation of myofibroblasts, inhibiting the activation of related pathways such as TGF-β1, SMAD, MAPK, and Wnt. However, most studies only target a specific stage of wound remodeling, neglecting the continuity of wound healing stages and the close connections between them. Furthermore, the pathways targeted are mostly common downstream pathways of myofibroblasts, which may also be abnormally expressed in many other common diseases.

[0007] Recent studies have indicated that the mechanotransmission-associated protein YAP is closely related to skin scarring and its formation. Inhibiting the YAP-TEAD interaction can prevent YAP-activated negative En1 myofibroblasts (ENFs) from becoming positive En1 myofibroblasts (EPFs). EPFs are responsible for normal tissue regeneration and repair, while EEPFs have been shown to be associated with scar formation in mice. Therefore, effectively blocking the YAP pathway to activate En1 may inhibit scar formation without affecting the tissue repair function of normal myofibroblasts.

[0008] Verteporfen is a commonly used photosensitizer, frequently used in phototherapy for tumors. It also induces apoptosis and inhibits autophagy. Recent studies have found that verteporfen can effectively block the YAP / TEAD pathway, increase VEGF expression, and promote angiogenesis, making it useful for treating age-related macular degeneration and other retinal diseases. This also has a positive impact on wound healing. However, verteporfen has certain phototoxic properties, making it difficult to use as an initiating wound treatment.

[0009] Inspired by the scarless wound healing of fetuses, it is necessary to ensure the cell proliferation and differentiation capacity at the wound site and a relatively moist external environment. Therefore, wound dressings need to have excellent water absorption and moisturizing properties to maintain a relatively moist environment on the wound surface and have good bactericidal effects to inhibit the abnormal proliferation of scar tissue and myofibroblasts. Hydrogel aqueous dressings based on natural polymers can well meet the above conditions. The drug release rate depends on the drug molecule size and pore size. The diameter of free drugs is only a few nanometers or even smaller, while the particle size of monolayer liposomes is between 100-1000 nm. Inspired by volume exclusion chromatography and chromatographic separation methods, the release rate of dopants in hydrogels can be ordered according to their size, that is, the larger the particle, the slower the release rate.

[0010] Hydrogels made from natural polymers such as gelatin, hyaluronic acid, and chitosan possess advantages including high water content, good breathability and moisture retention, easy degradation, and excellent biocompatibility. In particular, chitosan, with its high amino group content, can chemically bond with cell membrane surface proteins, achieving relatively good adhesion properties through chemical bonding. However, traditional chitosan has a high deacetylation rate and is only soluble in weak acids.

[0011] Therefore, the development of a wound dressing that is antibacterial, promotes rapid healing, and prevents scar formation for infected wounds has great market potential. Summary of the Invention

[0012] The purpose of this application is to address the problems of the prior art by providing an aqueous gel dressing with antibacterial and scar-preventing effects, and a method for its preparation.

[0013] To solve the technical problem, the technical solution of this application is: an aqueous gel dressing with antibacterial and scar prevention effects, comprising the following components:

[0014] The ingredients, by weight percentage, are: phenylboronic acid-grafted chitosan oligosaccharide, tannic acid, celecoxib, verteporfen liposomes, and deionized water: phenylboronic acid-grafted chitosan oligosaccharide 5-10%, tannic acid 5-10%, celecoxib 1-1.5%, verteporfen liposomes 0.01-0.03%, and deionized water to make up the balance.

[0015] The phenylboronic acid-grafted chitosan oligosaccharide is made from chitosan oligosaccharide and 3-fluoro-4-carboxyphenylboronic acid, with a weight ratio of chitosan oligosaccharide to 3-fluoro-4-carboxyphenylboronic acid of 20:4~6.

[0016] The verteporfen liposomes are made of liposome material and verteporfen, with a weight ratio of liposome material to verteporfen of 22~25:2.

[0017] Preferably, the preparation method of the phenylboronic acid grafted chitosan oligosaccharide is as follows:

[0018] 3-Fluoro-4-carboxyphenylboronic acid was dispersed in a buffer solution with pH 5.5-6.5 at 4℃, and N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide were added. The carboxyl groups were activated by continuous stirring for 1-4 h to obtain an activated mixture.

[0019] Then, chitosan oligosaccharide was added dropwise to the above activated mixture, and the mixture was stirred continuously at room temperature of 25°C for 12-32 hours. The mixture was then placed in a 1000 kDa dialysis bag and dialyzed with deionized water for 72 hours. After freeze-drying, phenylboronic acid-grafted chitosan oligosaccharide was obtained. The ratio of 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.

[0020] Preferably, the buffer solution is selected from 2-(N-morpholine)ethanesulfonic acid solution, dimethyl sulfoxide solution, or phosphate solution.

[0021] Preferably, the liposome material is selected from one or more of hydrogenated soybean phospholipids, phospholipid-polyethylene glycol 2000, and cholesterol.

[0022] Preferably, the method for preparing the verteporfen liposomes specifically includes:

[0023] Hydrogenated soybean phospholipids, phospholipid-polyethylene glycol 2000, cholesterol, and verteporfen were placed in the same round-bottom flask and fully dissolved in chloroform. The homogeneous liposome membranes were obtained by rotary distillation at 37°C under reduced pressure. The membranes were resuspended in ultrapure water and sonicated using a cell disruptor to obtain verteporfen liposomes. The ratio of hydrogenated soybean phospholipids:phospholipid-polyethylene glycol 2000:cholesterol:verteporfen:chloroform:ultrapure water was 21 mg:1 mg:0~3 mg:2 mg:6 mL:6 mL.

[0024] Preferably, the ultrasonic power and time of the cell disruptor are: 120~210W, 6~12min, 5s working, 5s rest.

[0025] Preferably, a method for preparing an aqueous gel dressing with antibacterial and scar-preventing effects includes the following steps:

[0026] Step 1: Prepare phenylboronic acid grafted chitosan oligosaccharide aqueous solution, celecoxib aqueous solution, tannic acid aqueous solution with pH adjusted to 8 by sodium hydroxide, and vertiporfen liposome aqueous solution;

[0027] Step 2: Mix the phenylboronic acid-grafted chitosan oligosaccharide aqueous solution and the celecoxib aqueous solution evenly to obtain mixed solution A;

[0028] Step 3: Mix the tannic acid aqueous solution and the vertiporin liposome aqueous solution evenly to obtain mixed solution B;

[0029] Step 4: Mix solution A and solution B in a volume ratio of 1:1;

[0030] Step 5: After thoroughly mixing the final mixture, pour it into a syringe and let it stand to obtain an aqueous gel dressing, which contains the following by weight percentage: 5-10% phenylboronic acid grafted chitosan oligosaccharide, 5-10% tannic acid, 1-1.5% celecoxib, and 0.01-0.03% verteporfen liposomes.

[0031] Preferably, the aqueous gel dressing is obtained by mixing solution A and solution B evenly and letting it stand at room temperature of 25°C for 2-3 minutes.

[0032] Preferably, the preparation method of the celecoxib aqueous solution is as follows: celecoxib is dissolved in a small amount of dimethyl sulfoxide, and then mixed with deionized water, wherein celecoxib:dimethyl sulfoxide:deionized water = 0.2g:2mL:8mL.

[0033] Compared with the prior art, the advantages of this application are:

[0034] (1) This application discloses an aqueous gel dressing with antibacterial and scar prevention effects. By introducing 3-fluoro-4-carboxyphenylboronic acid grafted with chitosan oligosaccharide, the phenylboronic acid bond forms a dynamic boron ester bond with a large number of catechol structures in the tannic acid solution. It responds to supramolecular forces such as hydrogen bonds to form a network gel structure. The boron ester bond can break in response to the high ROS level of the wound microenvironment and the acidic environment caused by bacterial infection, thereby efficiently releasing the cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug celecoxib. The verteporfen liposomes are limited by their large volume and remain in the dressing for a longer time, so 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.

[0035] (2) The dressing of this application has the characteristics of sequential release, synergistic immune regulation and cellular mechanical response regulation. Compared with traditional single or unregulated wound dressings, this application can not only promote wound healing, but also prevent wounds from leaving scars.

[0036] (3) In this application, verteporfen is encapsulated in liposomes, which can protect verteporfen on the one hand, and the larger particle size can greatly slow down its release rate on the other hand, thereby reducing cell phototoxicity by reducing the photosensitizing effect of verteporfen.

[0037] (4) The dressing preparation method of this application adopts chemical cross-linking method to cross-link through dynamic boron ester bond, which has the characteristic of responding to changes in wound microenvironment. The hydrogel prepared by cross-linking has good physicochemical properties. The modification method of dressing raw materials is simple, can be prepared and obtained by oneself and scaled up production, and is inexpensive and safe.

[0038] (5) The dressing prepared by the method of this application has good biological properties, is controllable and degradable, and has excellent cell compatibility. It also has good antibacterial, anti-inflammatory and ROS scavenging capabilities to promote scarless wound regeneration.

[0039] (6) The dressing obtained by the preparation method of the aqueous gel dressing with antibacterial and anti-scarring effects of this application has excellent injectability, can fit wound surfaces with different regularity, has short gelation time, high stability, low irritation to wounds and good biocompatibility and biodegradability. At the same time, the dressing can effectively fight bacterial infection and promote scarless healing of wounds. Attached Figure Description

[0040] Figure 1 This is an optical photograph taken by a scanning electron microscope (SEM) according to Embodiment 6 of this application;

[0041] Figure 2 An optical photograph of the aqueous gel dressing of Example 6 of this application;

[0042] Figure 3 These are optical photographs of the supernatant from the hemolytic experiments in Examples 3-6 of this application;

[0043] Figure 4 This is a bar chart showing the relative healing area of ​​Examples 5-6 of this application, Comparative Example 1, and commercially available products M3 and M4 at 14 days of wound healing in rats. Detailed Implementation

[0044] The present application is described in detail below with reference to the accompanying drawings and specific embodiments, but the present application is not limited to these embodiments. The present application covers any alternatives, modifications, equivalent methods, and solutions made within the spirit and scope of the present application. To provide the public with a thorough understanding of the present application, specific details are described in detail in the following embodiments, but those skilled in the art will fully understand the present application even without these detailed descriptions.

[0045] Natural polyphenols are compounds extracted from plants. Due to their excellent antibacterial, antioxidant, anti-inflammatory, bactericidal, and anti-aging properties, they have been increasingly studied in recent years. Their chemical structure is characterized by the presence of ortho- or para-catechin groups. For example, tannic acid has a hyperbranched structure and multiple catechol structures.

[0046] Hydrogels prepared using low molecular weight compounds typically have poor mechanical properties, are soft, and easily break under applied stress, making them generally unsuitable for applications requiring high mechanical strength, such as bone fillers and energy storage batteries. However, hydrogels with good plasticity are ideal for filling irregular skin wounds in the treatment of invasive wounds, achieving perfect wound coverage, isolating external bacteria, sequentially releasing drugs, and ensuring a moist environment and oxygen exchange.

[0047] Compared to chitosan, chitosan oligosaccharides exhibit higher biocompatibility and water solubility. Phenylboronic acid-modified chitosan oligosaccharides were prepared by reacting chitosan oligosaccharides with 3-fluoro-4-carboxyphenylboronic acid to regulate the chemical properties of the oligosaccharides and reduce their positive charge. Fluorine maintains the excellent hydrophilicity of the modified compound. Most importantly, the introduction of 3-fluoro-4-carboxyphenylboronic acid allows for the branching of numerous phenylboronic acid bonds on the side links of the compound. These bonds can form dynamic boron ester bonds through in-situ chemical crosslinking with the abundant catechol structures in tannic acid, and stabilize the three-dimensional structure of the hydrogel through supramolecular forces such as hydrogen bonding. Boron ester bonds are unstable chemical bonds, sensitive to pH and ROS, and will cleave responsively under high acidity or reactive oxygen species (ROS) levels. Therefore, this wound dressing not only meets the design requirements for irregular wounds and injectability but also possesses high designability and programmable control in response to changes in the wound microenvironment, thereby enabling on-demand drug release.

[0048] This 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.

[0049] The matrix materials of the excipients in this application all use FDA-approved or natural compounds with good biocompatibility and affinity. Among them, the side-chain amino groups of chitosan oligosaccharides have good bioadhesion, and both chitosan oligosaccharides and tannic acid have antioxidant and antibacterial effects. Compared with traditional single-function wound dressings, this application integrates multiple functions such as adhesion, self-healing, anti-inflammation, and antibacterial properties, providing a more comprehensive therapeutic effect.

[0050] This application discloses an aqueous gel dressing with antibacterial and scar-preventing effects, comprising the following components:

[0051] Phenylated boric acid-grafted chitosan oligosaccharide (PBA-COS), tannic acid (TA), celecoxib (CL), verteporfen liposomes (L-VP), and deionized water, by weight percentage: 5-10% phenylboronic acid-grafted chitosan oligosaccharide, 5-10% tannic acid, 1-1.5% celecoxib, 0.01-0.03% verteporfen liposomes, and deionized water to make up the balance;

[0052] The phenylboronic acid-grafted chitosan oligosaccharide is made from chitosan oligosaccharide and 3-fluoro-4-carboxyphenylboronic acid, with a weight ratio of chitosan oligosaccharide to 3-fluoro-4-carboxyphenylboronic acid of 20:4~6.

[0053] The verteporfen liposomes are made of liposome material and verteporfen, with a weight ratio of liposome material to verteporfen of 22~25:2.

[0054] Preferably, the preparation method of the phenylboronic acid grafted chitosan oligosaccharide is as follows:

[0055] 3-Fluoro-4-carboxyphenylboronic acid was dispersed in a buffer solution with pH 5.5-6.5 at 4℃, and N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide were added. The carboxyl groups were activated by continuous stirring for 1-4 h to obtain an activated mixture.

[0056] Then, chitosan oligosaccharide was added dropwise to the above activated mixture, and the mixture was stirred continuously at room temperature of 25°C for 12-32 hours. The mixture was then placed in a 1000 kDa dialysis bag and dialyzed with deionized water for 72 hours. After freeze-drying, phenylboronic acid-grafted chitosan oligosaccharide was obtained. The ratio of 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.

[0057] The pH can be 6.5, 6.2, 6.0, 5.8, or 5.5.

[0058] The stirring time for the first step can be 1 hour, 2 hours, 3 hours, 4 hours, etc.;

[0059] The second step of stirring time can refer to 12h, 16h, 20h, 24h, 28h, 32h, etc.;

[0060] Preferably, the buffer solution is selected from 2-(N-morpholine)ethanesulfonic acid solution, dimethyl sulfoxide solution, or phosphate solution.

[0061] Preferably, the liposome material is selected from one or more of hydrogenated soybean phospholipids, phospholipid-polyethylene glycol 2000, and cholesterol.

[0062] Preferably, the method for preparing the verteporfen liposomes specifically includes:

[0063] Hydrogenated soybean phospholipids, phospholipid-polyethylene glycol 2000, cholesterol, and verteporfen were placed in the same round-bottom flask and fully dissolved in chloroform. The homogeneous liposome membranes were obtained by rotary distillation at 37°C under reduced pressure. The membranes were resuspended in ultrapure water and sonicated using a cell disruptor to obtain verteporfen liposomes. The ratio of hydrogenated soybean phospholipids:phospholipid-polyethylene glycol 2000:cholesterol:verteporfen:chloroform:ultrapure water was 21 mg:1 mg:0~3 mg:2 mg:6 mL:6 mL.

[0064] The content ratio of hydrogenated soybean phospholipids: phospholipids-polyethylene glycol 2000: cholesterol: vertiporfin: chloroform: ultrapure water can be:

[0065] 21mg:1mg:0mg:2mg:6mL:6mL;

[0066] 21mg:1mg:1mg:2mg:6mL:6mL;

[0067] 21mg:1mg:2mg:2mg:6mL:6mL;

[0068] 21mg:1mg:3mg:2mg:6mL:6mL, etc.

[0069] Preferably, the ultrasonic power and time of the cell disruptor are: 120~210W, 6~12min, 5s working, 5s rest.

[0070] The ultrasound duration can be 6 min, 8 min, 10 min, 12 min, etc.;

[0071] The ultrasonic power can be 120W, 150W, 180W, 210W, etc.

[0072] By integrating verteporfen into liposome material, the damage to wounds caused by the photosensitivity of verteporfen is effectively prevented. Its larger size can also effectively avoid rapid release during dressing use, thereby enhancing the stability of drug release.

[0073] Preferably, a method for preparing an aqueous gel dressing with antibacterial and scar-preventing effects includes the following steps:

[0074] Step 1: Prepare phenylboronic acid grafted chitosan oligosaccharide aqueous solution, celecoxib aqueous solution, tannic acid aqueous solution with pH adjusted to 8 by sodium hydroxide, and vertiporfen liposome aqueous solution;

[0075] Step 2: Mix the phenylboronic acid-grafted chitosan oligosaccharide aqueous solution and the celecoxib aqueous solution evenly to obtain mixed solution A;

[0076] Step 3: Mix the tannic acid aqueous solution and the vertiporin liposome aqueous solution evenly to obtain mixed solution B;

[0077] Step 4: Mix solution A and solution B in a volume ratio of 1:1;

[0078] Step 5: After thoroughly mixing the final mixture, pour it into a syringe and let it stand to obtain an aqueous gel dressing, which contains the following by weight percentage: 5-10% phenylboronic acid grafted chitosan oligosaccharide, 5-10% tannic acid, 1-1.5% celecoxib, and 0.01-0.03% verteporfen liposomes.

[0079] Preferably, the aqueous gel dressing is obtained by mixing solution A and solution B evenly and letting it stand at room temperature of 25°C for 2-3 minutes.

[0080] Preferably, the preparation method of the celecoxib aqueous solution is as follows: celecoxib is dissolved in a small amount of dimethyl sulfoxide, and then mixed with deionized water, wherein celecoxib:dimethyl sulfoxide:deionized water = 0.2g:2mL:8mL.

[0081] Example 1

[0082] 1. Prepare a PBA-COS solution, denoted as solution A.

[0083] 2. Prepare a TA solution and adjust the pH to 8 with NaOH. This solution is denoted as solution B.

[0084] 3. Mix the above solutions A and B in a 1:1 ratio to obtain mixed solution C.

[0085] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain the dressing sample. The dressing contains 5% phenylboronic acid grafted with chitosan oligosaccharide and 5% tannic acid by weight percentage.

[0086] Example 2

[0087] 1. Prepare a PBA-COS solution, denoted as solution A.

[0088] 2. Prepare a TA solution and adjust the pH to 8 with NaOH. This solution is denoted as solution B.

[0089] 3. Mix the above solutions A and B in a 1:2 ratio to obtain mixed solution C.

[0090] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain the dressing sample. The dressing contains 5% phenylboronic acid grafted with chitosan oligosaccharide and 10% tannic acid by weight percentage.

[0091] Example 3

[0092] 1. Prepare a PBA-COS solution, denoted as solution A.

[0093] 2. Prepare a TA solution and adjust the pH to 8 with NaOH. This solution is denoted as solution B.

[0094] 3. Mix the above solutions A and B in a 2:1 ratio to obtain mixed solution C.

[0095] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain the dressing sample. The dressing contains 10% phenylboronic acid grafted with chitosan oligosaccharide and 5% tannic acid by weight percentage.

[0096] Example 4

[0097] 1. Prepare a PBA-COS solution containing 20 mg / mL Cl, denoted as solution A.

[0098] 2. Prepare a TA solution and adjust the pH to 8 with NaOH. This solution is denoted as solution B.

[0099] 3. Mix the above solutions A and B in a 1:1 ratio to obtain mixed solution C.

[0100] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain the dressing sample. The dressing contains 5% phenylboronic acid grafted with chitosan oligosaccharide, 5% tannic acid, and 1% celecoxib by weight percentage.

[0101] Example 5

[0102] 1. Prepare a PBA-COS solution, denoted as solution A.

[0103] 2. Prepare a TA solution containing L-VP, and adjust the pH to 8 with NaOH. This solution is denoted as solution B.

[0104] 3. Mix the above solutions A and B in a 1:1 ratio to obtain mixed solution C.

[0105] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain the dressing sample. The dressing contains 10% phenylboronic acid grafted chitosan oligosaccharide, 10% tannic acid, and 0.01% verteporfen liposomes by weight percentage.

[0106] Example 6

[0107] 1. Prepare a PBA-COS solution containing CL, denoted as solution A.

[0108] 2. Prepare a TA solution containing L-VP, and adjust the pH to 8 with NaOH. This solution is denoted as solution B.

[0109] 3. Mix the above solutions A and B in a 1:1 ratio to obtain mixed solution C.

[0110] 4. Quickly transfer the mixed solution C into a syringe and let it stand at 25°C for 2-3 minutes to obtain the dressing sample. The dressing contains 10% phenylboronic acid grafted chitosan oligosaccharide, 10% tannic acid, 1.5% celecoxib, and 0.03% verteporfen liposomes by weight percentage.

[0111] Comparative Example 1

[0112] 1. Prepare a phosphate buffer solution (PBS) with a pH of 7.4.

[0113] like Figure 1 The image shown is an SEM scan of Example 6 of this application, in which a three-dimensional mesh-like pore structure can be clearly observed. The mesh structure is dense and the pore size is uniform.

[0114] like Figure 2 The image shown is an optical photograph of the gel formation of the hydrogel prepared in Example 6 of this application.

[0115] like Figure 3 The image shown is an optical photograph of the supernatant from the hemolysis experiment in Examples 4-6 of this application. None of the components of this dressing cause significant hemolysis, demonstrating the excellent biocompatibility of the dressing.

[0116] like Figure 4 The bar chart shown represents the relative healing area of ​​Examples 5-6 of this application, Comparative Example 1, and commercially available products M3 and M4 at 14 days of wound healing in rats. In the bar chart, Control represents Comparative Example 1, M3 represents commercially available Chuanglening gel dressing, M4 represents commercially available Bourmann gel dressing, M5 represents Example 5, and M6 represents Example 6.

[0117] As can be seen from the figures, the wound healing effect of Examples 5-6 of this application is significantly better than that of Comparative Example 1, and also significantly better than that of commercially available products.

[0118] The preferred embodiments of this application have been described in detail above. However, this application is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of this application.

[0119] Many other changes and modifications can be made without departing from the concept and scope of this application. It should be understood that this application is not limited to the specific embodiments, and the scope of this application is defined by the appended claims.

Claims

1. A water-based gel dressing with antibacterial and scar-preventing effects, characterized in that, Includes the following components: The ingredients, by weight percentage, are: phenylboronic acid-grafted chitosan oligosaccharide, tannic acid, celecoxib, verteporfen liposomes, and deionized water: phenylboronic acid-grafted chitosan oligosaccharide 5-10%, tannic acid 5-10%, celecoxib 1-1.5%, verteporfen liposomes 0.01-0.03%, and deionized water to make up the balance. The phenylboronic acid-grafted chitosan oligosaccharide is made from chitosan oligosaccharide and 3-fluoro-4-carboxyphenylboronic acid, with a weight ratio of chitosan oligosaccharide to 3-fluoro-4-carboxyphenylboronic acid of 20:4~6. The verteporfen liposomes are made of liposome material and verteporfen, with a weight ratio of liposome material to verteporfen of 22~25:

2. The specific method for preparing the phenylboronic acid-grafted chitosan oligosaccharide is as follows: 3-Fluoro-4-carboxyphenylboronic acid was dispersed in a buffer solution with pH 5.5-6.5 at 4℃, and N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide were added. The carboxyl groups were activated by continuous stirring for 1-4 h to obtain an activated mixture. Then, chitosan oligosaccharide was added dropwise to the above activated mixture, and the mixture was stirred continuously at room temperature (25°C) for 12-32 hours. The mixture was then dialyzed with deionized water in a dialysis bag for 72 hours and freeze-dried to obtain phenylboronic acid-grafted chitosan oligosaccharide. The ratio of 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.

2. The aqueous gel dressing with antibacterial and scar-preventing effects according to claim 1, characterized in that, The buffer solution is selected from 2-(N-morpholine)ethanesulfonic acid solution, dimethyl sulfoxide solution, or phosphate solution.

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

4. The aqueous gel dressing with antibacterial and scar-preventing effects according to claim 3, characterized in that, The specific method for preparing the vertipofen liposomes is as follows: Hydrogenated soybean phospholipids, phospholipid-polyethylene glycol 2000, cholesterol, and verteporfen were placed in the same round-bottom flask and fully dissolved in chloroform. The homogeneous liposome membranes were obtained by rotary distillation at 37°C under reduced pressure. The membranes were resuspended in ultrapure water and sonicated using a cell disruptor to obtain verteporfen liposomes. The ratio of hydrogenated soybean phospholipids:phospholipid-polyethylene glycol 2000:cholesterol:verteporfen:chloroform:ultrapure water was 21 mg:1 mg:0~3 mg:2 mg:6 mL:6 mL.

5. The aqueous gel dressing with antibacterial and scar-preventing effects according to claim 4, characterized in that, The ultrasonic power and time of the cell disruptor are: 120~210W, 6~12min, 5s working, 5s rest.

6. A method for preparing the aqueous gel dressing with antibacterial and scar-preventing effects as described in claim 1, characterized in that, Includes the following steps: Step 1: Prepare phenylboronic acid grafted chitosan oligosaccharide aqueous solution, celecoxib aqueous solution, tannic acid aqueous solution with pH adjusted to 8 by sodium hydroxide, and vertiporfen liposome aqueous solution; Step 2: Mix the phenylboronic acid-grafted chitosan oligosaccharide aqueous solution and the celecoxib aqueous solution evenly to obtain mixed solution A; Step 3: Mix the tannic acid aqueous solution and the vertiporin liposome aqueous solution evenly to obtain mixed solution B; Step 4: Mix solution A and solution B in a volume ratio of 1:1; Step 5: After thoroughly mixing the final mixture, pour it into a syringe and let it stand to obtain an aqueous gel dressing.

7. The preparation method according to claim 6, characterized in that, Mix solution A and solution B thoroughly and let stand at room temperature (25°C) for 2-3 minutes to obtain an aqueous gel dressing.

8. The preparation method according to claim 6, characterized in that, The method for preparing the celecoxib aqueous solution is as follows: celecoxib is dissolved in a small amount of dimethyl sulfoxide, and then mixed with deionized water, wherein celecoxib:dimethyl sulfoxide:deionized water = 0.2g:2mL:8mL.

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