Dressing for promoting pain relieving and regeneration of burn wound and preparation method thereof

Abstract

The invention discloses a dressing for promoting pain relief and regeneration of burn wounds and a preparation method of the dressing. The dressing comprises a drug delivery carrier and slow-release multi-effect hydrogel loaded on the drug delivery carrier, the slow-release multi-effect hydrogel is prepared from the following raw materials in parts by weight: 100 parts of water, 7 to 35 parts of multi-effect slow-release microspheres, 3.5 to 10 parts of sodium carboxymethyl cellulose, 2.5 to 8 parts of sodium hyaluronate and 0.5 to 4 parts of glycerol. The dressing provided by the invention has the effects of relieving wound pain, promoting wound regeneration and inhibiting and killing bacteria, the effect of the dressing is long-acting by realizing slow release of various active components (antibacterial carbon dots, silver nanoparticles and bletilla striata polysaccharide), and the dressing has a good application prospect by virtue of matching of the active components and the slow-release effect of the active components. The nursing and treatment effects of burn wounds can be effectively improved, and the application prospect is very good.

Description

Technical Field

[0001] The present invention relates to the pharmaceutical field, and in particular to a dressing for promoting analgesia and regeneration of burn wounds and a preparation method thereof. Background Art

[0002] Burns generally refer to tissue damage caused by heat, including hot liquids (water, soup, oil, etc.), steam, high-temperature gases, flames, hot metal liquids or solids (such as molten steel, steel ingots), and strong radioactive radiation. Burns primarily involve the skin and / or mucous membranes. In severe cases, they can also damage subcutaneous and / or submucosal tissues, such as muscles, bones, joints, and even internal organs. Burn dressings are medical materials used to cover burn wounds to protect them and promote healing. The core of burn dressings is to protect the wound surface, prevent infection, and promote healing. Common burn dressings include hydrogel dressings, silicone dressings, silver ion dressings, and biological dressings. Hydrogel dressings can provide a moist environment, relieve pain, and promote epidermal regeneration; silver ion dressings contain antibacterial ingredients and can also provide antibacterial properties.

[0003] Bletilla striata polysaccharide, a major extract from Bletilla striata, has been shown to shorten bleeding and clotting times, promote wound healing, and alleviate wound pain. For example, patent CN107496977B discloses a liquid dressing made from a pure natural plant extract and its preparation method; patent CN119033994A discloses a traditional Chinese medicine antibacterial double-layer hydrogel dressing and its preparation method; and patent CN116327799A discloses a method for preparing a Bletilla striata extract and its use in the preparation of antibacterial products.

[0004] When used in traditional dressings, Bletilla striata polysaccharide is released rapidly in the initial stage, which can easily lead to excessive concentration on the wound surface, resulting in waste and even negative effects. Furthermore, due to the rapid release of Bletilla striata polysaccharide, it cannot fully exert its function and cannot provide long-term analgesia and promote wound healing, which seriously limits its effectiveness. Furthermore, due to its short expiration time, frequent dressing changes are required, increasing care costs and patient suffering.

[0005] Therefore, it is necessary to improve the existing technology to provide a more reliable solution. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a dressing that promotes analgesia and regeneration of burn wounds and a preparation method thereof in view of the deficiencies in the above-mentioned prior art.

[0007] To solve the above technical problems, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides a dressing for promoting analgesia and regeneration of burn wounds, comprising a drug delivery carrier and a sustained-release multi-effect hydrogel loaded on the drug delivery carrier;

[0008] The sustained-release multi-effect hydrogel comprises the following raw materials in parts by weight: 100 parts of water, 7-35 parts of multi-effect sustained-release microspheres, 3.5-10 parts of sodium carboxymethyl cellulose, 2.5-8 parts of sodium hyaluronate, and 0.5-4 parts of glycerol;

[0009] The multi-effect sustained-release microspheres are prepared by the following method:

[0010] S1, loading antibacterial carbon dots on mesoporous silica hollow spheres to obtain an antibacterial carrier;

[0011] S2, in situ depositing silver nanoparticles on the antibacterial carrier to obtain a composite antibacterial carrier;

[0012] S3. Bletilla striata polysaccharide is loaded on the composite antibacterial carrier by the impregnation method to obtain multi-effect sustained-release microspheres.

[0013] Preferably, step S1 is specifically:

[0014] Take the mesoporous silica hollow spheres and add them into deionized water, ultrasonically disperse them, then add chitosan, salicylic acid, vitamin C and ethanol, stir, transfer the obtained mixture into a reactor, react under heating, filter, wash and dry after the reaction is completed to obtain an antibacterial carrier.

[0015] Preferably, step S1 is specifically:

[0016] Take 1-4g of mesoporous silica hollow spheres and add them to 75-300mL of deionized water, ultrasonically disperse them for 0.5-2h, then add 0.42-1.7g of chitosan, 0.35-1.4g of salicylic acid, 0.15-0.7g of vitamin C, and 25-100mL of ethanol, stir for 30-90min, transfer the resulting mixture into a reactor, react at 160-200℃ for 3.5-10h, filter, wash the solid product with deionized water, and vacuum dry at 80-100℃ for 6-24h to obtain an antibacterial carrier.

[0017] Preferably, step S2 is specifically:

[0018] An antibacterial carrier is added to a silver nitrate solution and ultrasonically dispersed, and then ammonia water is added dropwise to the obtained dispersion until the precipitate just disappears to obtain a mixture of the antibacterial carrier and the silver ammonium solution. Glucose solution and β-cyclodextrin are added to the mixture, and the mixture is reacted under heating. After the reaction is completed, the mixture is filtered, washed, and dried to obtain a composite antibacterial carrier.

[0019] Preferably, step S2 is specifically:

[0020] Take 0.5-2g of the antibacterial carrier and add it to 25-100mL of a silver nitrate solution with a concentration of 0.05-0.2mol / L, ultrasonically disperse it for 15-60min, then add 2.5-10wt% ammonia water to the obtained dispersion until the precipitate just disappears to obtain a mixture of the antibacterial carrier and the silver ammonium solution, add 5-20mL of a glucose solution with a concentration of 0.25-1mol / L and 1-4g of β-cyclodextrin to the mixture, react at 90-110°C for 15-60min, filter, wash the solid product with ethanol and deionized water in sequence, and vacuum dry at 70-90°C for 4-12h to obtain a composite antibacterial carrier.

[0021] Preferably, step S3 is specifically:

[0022] The composite antibacterial carrier is added to deionized water and ultrasonically dispersed, and then Bletilla striata polysaccharide is added and stirred. The mixture is then sealed and shaken, and the seal is removed. The mixture is heated until the solvent is evaporated to dryness to obtain multi-effect sustained-release microspheres.

[0023] Preferably, step S3 is specifically:

[0024] Take 0.5-2g of the composite antibacterial carrier and add it to 25-100mL of deionized water, ultrasonically disperse it for 15-60min, then add 0.125-0.5g of Bletilla striata polysaccharide, stir it for 0.5-2h, then seal it, shake it on a shaker at 40-60℃ for 6-24h, remove the seal, and heat it at 90-100℃ until the solvent evaporates to obtain multi-effect sustained-release microspheres.

[0025] Preferably, the multi-effect sustained-release microspheres are prepared by the following method:

[0026] S1. Loading antibacterial carbon dots on mesoporous silica hollow spheres:

[0027] 2 g of mesoporous silica hollow spheres were added to 150 mL of deionized water and ultrasonically dispersed for 1 h. Then, 0.85 g of chitosan, 0.69 g of salicylic acid, 0.352 g of vitamin C, and 50 mL of ethanol were added and stirred for 45 min. The resulting mixture was transferred to a reactor and reacted at 180 ° C for 7 h. After filtration, the solid product was washed with deionized water and vacuum dried at 90 ° C for 12 h to obtain an antibacterial carrier.

[0028] S2. In situ deposition of silver nanoparticles on the antibacterial carrier:

[0029] 1 g of the antibacterial carrier was added to 50 mL of a 0.1 mol / L silver nitrate solution and ultrasonically dispersed for 30 minutes. Then, 5 wt% ammonia water was added dropwise to the resulting dispersion until the precipitate just disappeared to obtain a mixture of the antibacterial carrier and the silver ammonium solution. 10 mL of a 0.5 mol / L glucose solution and 2 g of β-cyclodextrin were added to the mixture, and the mixture was reacted at 100°C for 30 minutes. The mixture was filtered, and the solid product was washed with ethanol and deionized water in sequence, and vacuum dried at 80°C for 8 hours to obtain a composite antibacterial carrier.

[0030] S3. Loading Bletilla striata polysaccharide on the composite antibacterial carrier by impregnation method:

[0031] Take 1g of the composite antibacterial carrier and add it to 50mL of deionized water, ultrasonically disperse it for 30min, then add 0.25g of Bletilla striata polysaccharide and stir it for 1h. Then seal it and shake it on a shaker at 50℃ for 12h. Unseal it and heat it at 100℃ until the solvent evaporates to obtain multi-effect sustained-release microspheres.

[0032] A second aspect of the present invention provides a method for preparing the above-mentioned dressing for promoting analgesia and regeneration of burn wounds, comprising the following steps:

[0033] 1) adding multi-effect sustained-release microspheres to a portion of deionized water and ultrasonically dispersing the microspheres to obtain a microsphere dispersion; adding sodium carboxymethyl cellulose and glycerol to the remaining deionized water and stirring; and adding the resulting product to the microsphere dispersion while stirring to obtain a mixture 1;

[0034] 2) adding sodium hyaluronate to the mixture 1 under stirring, stirring and reacting at room temperature, and allowing to stand to obtain a gel solution;

[0035] 3) The gel is coated on the surface of the drug delivery carrier and dried to obtain a dressing.

[0036] Preferably, the method for preparing the dressing for promoting analgesia and regeneration of burn wounds comprises the following steps:

[0037] 1) adding multi-effect sustained-release microspheres to deionized water accounting for 3 / 4 of the total mass and ultrasonically dispersing for 30-60 minutes to obtain a microsphere dispersion; adding sodium carboxymethyl cellulose and glycerol to the remaining deionized water and stirring for 5-30 minutes; and adding the resulting product to the microsphere dispersion with stirring, stirring for 0.5-2 hours to obtain a mixture 1;

[0038] 2) adding sodium hyaluronate to mixture 1 under stirring, reacting at room temperature for 1-4 hours, and allowing to stand for 6-24 hours to obtain a gel solution;

[0039] 3) Apply the gel to the surface of the drug carrier, and control the wet coating amount to 1.5-5g / cm 2 , and dried at 60-70°C for 2-8h to obtain a dressing.

[0040] The beneficial effects of the present invention are:

[0041] The present invention provides a dressing for promoting analgesia and regeneration of burn wounds and a preparation method thereof. The dressing has the effects of relieving wound pain, promoting wound regeneration, and inhibiting and sterilizing bacteria. The dressing achieves a long-lasting effect by achieving sustained release of multiple active components (antibacterial carbon dots, silver nanoparticles, and bletilla striata polysaccharide). The combination of the active components and their sustained release effect can effectively improve the nursing and treatment effects of burn wounds, and has a good application prospect.

[0042] The multi-effect sustained-release microspheres prepared in the present invention can provide the dressing system with a sustained-release function of the active ingredient, Bletilla striata polysaccharide, thereby enabling its efficacy to be more fully exerted, prolonging its duration of action, and avoiding the problem of excessively high drug concentration on the wound surface during the initial application phase, which may negatively impact the wound surface.

[0043] In the multi-effect sustained-release microspheres provided by the present invention:

[0044] First, antibacterial carbon dots are loaded onto hollow mesoporous silica spheres to produce an antibacterial carrier. These antibacterial carbon dots are synthesized in situ via a one-pot hydrothermal reaction using chitosan, salicylic acid, and vitamin C as carbon sources. The rich pore structure and large specific surface area of ​​the hollow mesoporous silica spheres enable uniform and extensive loading of the carbon dots, effectively preventing the agglomeration of the nanosized carbon dots. These carbon dots inherit the antibacterial properties of their precursor materials, chitosan and salicylic acid, and, thanks to the microporous sustained-release properties of the hollow mesoporous silica spheres, provide a long-lasting antibacterial effect for the dressing system.

[0045] Then, the silver ammonium solution was reduced by the green reducing agent glucose on the antibacterial carrier to load uniformly distributed silver nanoparticles on the antibacterial carrier, thereby obtaining a composite antibacterial carrier. This composite antibacterial carrier can further enhance the antibacterial performance. Similarly, the pore structure of the mesoporous silica hollow spheres can also achieve sustained release in the dressing system.

[0046] Finally, bletilla striata polysaccharide was loaded on the composite antibacterial carrier by the impregnation method. Under the adsorption action of the composite antibacterial carrier, bletilla striata polysaccharide entered the micropores of the mesoporous silica hollow spheres, thereby realizing the sustained release of bletilla striata polysaccharide and providing the dressing system with long-term function of relieving burn wound pain and promoting burn wound regeneration. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 This is the release curve of Bletilla striata polysaccharide released from the multi-effect sustained-release microspheres prepared in Example 1;

[0048] Figure 2 The analgesic effect test results of the dressing prepared in Example 1;

[0049] Figure 3 The wound healing rate test results of the dressings prepared in Examples 1-3 and Comparative Examples 1-3 after 10 days of application;

[0050] Figure 4 These are the test results of the antibacterial performance of the dressings prepared in Examples 1-3 and Comparative Examples 1-3. DETAILED DESCRIPTION

[0051] The present invention is further described in detail below with reference to the embodiments so that those skilled in the art can implement the invention with reference to the description.

[0052] It should be understood that terms such as “having”, “including” and “comprising” used herein do not preclude the existence or addition of one or more other elements or combinations thereof.

[0053] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Materials and reagents used in the following examples are commercially available unless otherwise specified. In the following examples, where specific conditions are not specified, the experiments were conducted under conventional conditions or those recommended by the manufacturer. Reagents and instruments used, where the manufacturer is not specified, are commercially available conventional products.

[0054] The main sources of raw materials involved in the following examples and comparative examples are as follows:

[0055] Sodium carboxymethyl cellulose, glycerol, Tianjin Damao Chemical Reagent Partnership;

[0056] Sodium hyaluronate, Xi'an Tianfeng Biotechnology Co., Ltd.;

[0057] Mesoporous silica hollow spheres, particle size 200-300nm, pore size 2-3nm, specific surface area > 400m 2 / g, pore volume>0.4cm 2 / g;Zhoran Environmental Technology (Dalian) Co., Ltd.;

[0058] Chitosan (90% deacetylation degree, Shanxi Jinyang Pharmaceutical Excipients Co., Ltd.), Tianjin Haolian Technology Development Co., Ltd.;

[0059] Bletilla striata polysaccharide, purity>98% (HPLC), fineness 200 mesh, Fufeng Sinuote Biotechnology Co., Ltd.

[0060] β-Cyclodextrin, CAS No. 7585-39-9, molecular weight 1135, density 1.6±0.1 g / cm3, Tianjin Damao Chemical Reagent Partnership Enterprise (Limited Partnership).

[0061] Example 1

[0062] A dressing for promoting analgesia and regeneration of burn wounds, comprising a drug delivery carrier and a sustained-release multi-effect hydrogel loaded on the drug delivery carrier; the sustained-release multi-effect hydrogel comprises the following raw materials in parts by weight: 100 parts water, 18 parts multi-effect sustained-release microspheres, 7 parts sodium carboxymethyl cellulose, 5 parts sodium hyaluronate, and 2.5 parts glycerol;

[0063] The preparation method of the dressing comprises the following steps:

[0064] 1) adding the multi-effect sustained-release microspheres to deionized water accounting for 3 / 4 of the total mass (i.e., 75 parts by weight) and ultrasonically dispersing for 45 minutes to obtain a microsphere dispersion; adding sodium carboxymethyl cellulose and glycerol to the remaining deionized water and stirring for 15 minutes; and adding the resulting product to the microsphere dispersion with stirring, stirring for 1 hour to obtain a mixture 1;

[0065] 2) Sodium hyaluronate was added to the mixture 1 under stirring, and the mixture was stirred at room temperature for 2 hours, and allowed to stand for 12 hours to obtain a gel solution;

[0066] 3) Apply the gel on the surface of the drug carrier, and control the wet coating amount to 2.5g / cm 2 , and dried at 65°C for 4 h to obtain a dressing.

[0067] Multi-effect sustained-release microspheres are prepared by the following method:

[0068] S1. Loading antibacterial carbon dots on mesoporous silica hollow spheres:

[0069] 2 g of mesoporous silica hollow spheres were added to 150 mL of deionized water and ultrasonically dispersed for 1 h. Then, 0.85 g of chitosan, 0.69 g of salicylic acid, 0.352 g of vitamin C, and 50 mL of ethanol were added and stirred for 45 min. The resulting mixture was transferred to a reactor and reacted at 180 ° C for 7 h. After filtration, the solid product was washed with deionized water and vacuum dried at 90 ° C for 12 h to obtain an antibacterial carrier.

[0070] S2. In situ deposition of silver nanoparticles on the antibacterial carrier:

[0071] 1 g of the antibacterial carrier was added to 50 mL of a 0.1 mol / L silver nitrate solution and ultrasonically dispersed for 30 minutes. Then, 5 wt% ammonia water was added dropwise to the resulting dispersion until the precipitate just disappeared to obtain a mixture of the antibacterial carrier and the silver ammonium solution. 10 mL of a 0.5 mol / L glucose solution and 2 g of β-cyclodextrin were added to the mixture, and the mixture was reacted at 100°C for 30 minutes. The mixture was filtered, and the solid product was washed with ethanol and deionized water in sequence, and vacuum dried at 80°C for 8 hours to obtain a composite antibacterial carrier.

[0072] S3. Loading Bletilla striata polysaccharide on the composite antibacterial carrier by impregnation method:

[0073] Take 1g of the composite antibacterial carrier and add it to 50mL of deionized water, ultrasonically disperse it for 30min, then add 0.25g of Bletilla striata polysaccharide and stir it for 1h. Then seal it and shake it on a shaker at 50℃ for 12h. Unseal it and heat it at 100℃ until the solvent evaporates to obtain multi-effect sustained-release microspheres.

[0074] Performance test of multi-effect sustained-release microspheres in releasing Bletilla striata polysaccharide:

[0075] 20 g of the multi-effect sustained-release microspheres prepared in this example were added to 1 L of deionized water and ultrasonically dispersed for 1 h to obtain a test solution. The concentration of Bletilla striata polysaccharide in the test solution was then detected every 6 h, and the release amount of Bletilla striata polysaccharide was calculated. The release curve was plotted with the cumulative value of the release percentage as the ordinate and the treatment time as the abscissa. Q t represents the cumulative release amount within time t, and Q0 represents the total loading amount of Bletilla striata polysaccharide in the multi-effect sustained-release microspheres (calculated by deducting the total amount of Bletilla striata polysaccharide added from the remaining amount after immersion).

[0076] The test results are as follows Figure 1 As shown, it can be seen that the multi-effect sustained-release microspheres prepared in this example can achieve long-term sustained release of Bletilla striata polysaccharide, and the release time is greater than 84h.

[0077] Example 2

[0078] A dressing for promoting analgesia and regeneration of burn wounds, comprising a drug delivery carrier and a sustained-release multi-effect hydrogel loaded on the drug delivery carrier; the sustained-release multi-effect hydrogel comprises the following raw materials in parts by weight: 100 parts water, 18 parts multi-effect sustained-release microspheres, 7 parts sodium carboxymethyl cellulose, 5 parts sodium hyaluronate, and 2.5 parts glycerol;

[0079] The preparation method of the dressing comprises the following steps:

[0080] 1) adding the multi-effect sustained-release microspheres to deionized water accounting for 3 / 4 of the total mass (i.e., 75 parts by weight) and ultrasonically dispersing for 45 minutes to obtain a microsphere dispersion; adding sodium carboxymethyl cellulose and glycerol to the remaining deionized water and stirring for 15 minutes; and adding the resulting product to the microsphere dispersion with stirring, stirring for 1 hour to obtain a mixture 1;

[0081] 2) Sodium hyaluronate was added to the mixture 1 under stirring, and the mixture was stirred at room temperature for 2 hours, and allowed to stand for 12 hours to obtain a gel solution;

[0082] 3) Apply the gel on the surface of the drug carrier, and control the wet coating amount to 2.5g / cm 2 , and dried at 65°C for 4 h to obtain a dressing.

[0083] Multi-effect sustained-release microspheres are prepared by the following method:

[0084] S1. Loading antibacterial carbon dots on mesoporous silica hollow spheres:

[0085] 2 g of mesoporous silica hollow spheres were added to 150 mL of deionized water and ultrasonically dispersed for 1 h. Then, 0.85 g of chitosan, 0.69 g of salicylic acid, 0.352 g of vitamin C, and 50 mL of ethanol were added and stirred for 45 min. The resulting mixture was transferred to a reactor and reacted at 180 ° C for 7 h. After filtration, the solid product was washed with deionized water and vacuum dried at 90 ° C for 12 h to obtain an antibacterial carrier.

[0086] S2. In situ deposition of silver nanoparticles on the antibacterial carrier:

[0087] 1 g of the antibacterial carrier was added to 50 mL of a 0.1 mol / L silver nitrate solution and ultrasonically dispersed for 30 minutes. Then, 5 wt% ammonia water was added dropwise to the resulting dispersion until the precipitate just disappeared to obtain a mixture of the antibacterial carrier and the silver ammonium solution. 10 mL of a 0.5 mol / L glucose solution and 2 g of β-cyclodextrin were added to the mixture, and the mixture was reacted at 100°C for 30 minutes. The mixture was filtered, and the solid product was washed with ethanol and deionized water in sequence, and vacuum dried at 80°C for 8 hours to obtain a composite antibacterial carrier.

[0088] S3. Loading Bletilla striata polysaccharide on the composite antibacterial carrier by impregnation method:

[0089] Take 1g of the composite antibacterial carrier and add it to 50mL of deionized water, ultrasonically disperse it for 30min, then add 0.20g of Bletilla striata polysaccharide and stir it for 1h. Then seal it and shake it on a shaker at 50℃ for 12h. Unseal it and heat it at 100℃ until the solvent evaporates to obtain multi-effect sustained-release microspheres.

[0090] Example 3

[0091] A dressing for promoting analgesia and regeneration of burn wounds, comprising a drug delivery carrier and a sustained-release multi-effect hydrogel loaded on the drug delivery carrier; the sustained-release multi-effect hydrogel comprises the following raw materials in parts by weight: 100 parts water, 18 parts multi-effect sustained-release microspheres, 7 parts sodium carboxymethyl cellulose, 5 parts sodium hyaluronate, and 2.5 parts glycerol;

[0092] The preparation method of the dressing comprises the following steps:

[0093] 1) adding the multi-effect sustained-release microspheres to deionized water accounting for 3 / 4 of the total mass (i.e., 75 parts by weight) and ultrasonically dispersing for 45 minutes to obtain a microsphere dispersion; adding sodium carboxymethyl cellulose and glycerol to the remaining deionized water and stirring for 15 minutes; and adding the resulting product to the microsphere dispersion with stirring, stirring for 1 hour to obtain a mixture 1;

[0094] 2) Sodium hyaluronate was added to the mixture 1 under stirring, and the mixture was stirred at room temperature for 2 hours, and allowed to stand for 12 hours to obtain a gel solution;

[0095] 3) Apply the gel on the surface of the drug carrier, and control the wet coating amount to 2.5g / cm 2 , and dried at 65°C for 4 h to obtain a dressing.

[0096] Multi-effect sustained-release microspheres are prepared by the following method:

[0097] S1. Loading antibacterial carbon dots on mesoporous silica hollow spheres:

[0098] 2.3 g of mesoporous silica hollow spheres were added to 150 mL of deionized water and ultrasonically dispersed for 1 h. Then, 0.85 g of chitosan, 0.69 g of salicylic acid, 0.352 g of vitamin C, and 50 mL of ethanol were added and stirred for 45 min. The resulting mixture was transferred to a reactor and reacted at 180 ° C for 7 h. After filtration, the solid product was washed with deionized water and vacuum dried at 90 ° C for 12 h to obtain an antibacterial carrier.

[0099] S2. In situ deposition of silver nanoparticles on the antibacterial carrier:

[0100] 1 g of the antibacterial carrier was added to 50 mL of a 0.1 mol / L silver nitrate solution and ultrasonically dispersed for 30 minutes. Then, 5 wt% ammonia water was added dropwise to the resulting dispersion until the precipitate just disappeared to obtain a mixture of the antibacterial carrier and the silver ammonium solution. 10 mL of a 0.5 mol / L glucose solution and 2 g of β-cyclodextrin were added to the mixture, and the mixture was reacted at 100°C for 30 minutes. The mixture was filtered, and the solid product was washed with ethanol and deionized water in sequence, and vacuum dried at 80°C for 8 hours to obtain a composite antibacterial carrier.

[0101] S3. Loading Bletilla striata polysaccharide on the composite antibacterial carrier by impregnation method:

[0102] Take 1g of the composite antibacterial carrier and add it to 50mL of deionized water, ultrasonically disperse it for 30min, then add 0.25g of Bletilla striata polysaccharide and stir it for 1h. Then seal it and shake it on a shaker at 50℃ for 12h. Unseal it and heat it at 100℃ until the solvent evaporates to obtain multi-effect sustained-release microspheres.

[0103] Comparative Example 1

[0104] A dressing for promoting analgesia and regeneration of burn wounds, comprising a drug delivery carrier and a sustained-release multi-effect hydrogel loaded on the drug delivery carrier; the sustained-release multi-effect hydrogel comprises the following raw materials in parts by weight: 100 parts water, 14.5 parts sustained-release microspheres, 3.5 parts bletilla striata polysaccharide, 7 parts sodium carboxymethyl cellulose, 5 parts sodium hyaluronate, and 2.5 parts glycerol;

[0105] The preparation method of the dressing comprises the following steps:

[0106] 1) adding the sustained-release microspheres to deionized water accounting for 3 / 4 of the total mass (i.e., 75 parts by weight) and ultrasonically dispersing for 45 minutes to obtain a microsphere dispersion; adding bletilla striata polysaccharide, sodium carboxymethyl cellulose, and glycerol to the remaining deionized water and stirring for 15 minutes; and adding the resulting product to the microsphere dispersion with stirring, stirring for 1 hour to obtain a mixture 1;

[0107] 2) Sodium hyaluronate was added to the mixture 1 under stirring, and the mixture was stirred at room temperature for 2 hours, and allowed to stand for 12 hours to obtain a gel solution;

[0108] 3) Apply the gel on the surface of the drug carrier, and control the wet coating amount to 2.5g / cm 2 , and dried at 65°C for 4 h to obtain a dressing.

[0109] Comparative Example 2

[0110] The only difference between this example and Example 1 is that:

[0111] Multi-effect sustained-release microspheres are prepared by the following method:

[0112] S1. In situ deposition of silver nanoparticles on mesoporous silica hollow spheres:

[0113] 1 g of hollow mesoporous silica spheres was added to 50 mL of a 0.1 mol / L silver nitrate solution and ultrasonically dispersed for 30 min. 5 wt% ammonia water was then added dropwise to the resulting dispersion until the precipitate just disappeared, thereby obtaining a mixture of an antibacterial carrier and silver ammonium solution. 10 mL of a 0.5 mol / L glucose solution and 2 g of β-cyclodextrin were added to the mixture, and the mixture was reacted at 100° C. for 30 min. The mixture was filtered, and the solid product was washed with ethanol and deionized water in sequence, and vacuum dried at 80° C. for 8 h to obtain a composite antibacterial carrier.

[0114] S3. Loading Bletilla striata polysaccharide on the composite antibacterial carrier by impregnation method:

[0115] Take 1g of the composite antibacterial carrier and add it to 50mL of deionized water, ultrasonically disperse it for 30min, then add 0.25g of Bletilla striata polysaccharide and stir it for 1h. Then seal it and shake it on a shaker at 50℃ for 12h. Unseal it and heat it at 100℃ until the solvent evaporates to obtain multi-effect sustained-release microspheres.

[0116] Comparative Example 3

[0117] The only difference between this example and Example 1 is that:

[0118] Multi-effect sustained-release microspheres are prepared by the following method:

[0119] S1. Loading antibacterial carbon dots on mesoporous silica hollow spheres:

[0120] 2 g of mesoporous silica hollow spheres were added to 150 mL of deionized water and ultrasonically dispersed for 1 h. Then, 0.85 g of chitosan, 0.69 g of salicylic acid, 0.352 g of vitamin C, and 50 mL of ethanol were added and stirred for 45 min. The resulting mixture was transferred to a reactor and reacted at 180 ° C for 7 h. After filtration, the solid product was washed with deionized water and vacuum dried at 90 ° C for 12 h to obtain an antibacterial carrier.

[0121] S2. Loading Bletilla striata polysaccharide on the antibacterial carrier by impregnation method:

[0122] Take 1g of antibacterial carrier and add it to 50mL of deionized water, ultrasonically disperse it for 30min, then add 0.25g of Bletilla striata polysaccharide and stir it for 1h. Then seal it and shake it on a shaker at 50℃ for 12h. Unseal it and heat it at 100℃ until the solvent evaporates to obtain multi-effect sustained-release microspheres.

[0123] Comparative Example 4

[0124] A dressing for promoting analgesia and regeneration of burn wounds, comprising a drug delivery carrier and a sustained-release multi-effect hydrogel loaded on the drug delivery carrier; the sustained-release multi-effect hydrogel comprises the following raw materials in parts by weight: 100 parts water, 18 parts sustained-release microspheres, 7 parts sodium carboxymethyl cellulose, 5 parts sodium hyaluronate, and 2.5 parts glycerol;

[0125] The preparation method of the dressing comprises the following steps:

[0126] 1) adding the multi-effect sustained-release microspheres to deionized water accounting for 3 / 4 of the total mass (i.e., 75 parts by weight) and ultrasonically dispersing for 45 minutes to obtain a microsphere dispersion; adding sodium carboxymethyl cellulose and glycerol to the remaining deionized water and stirring for 15 minutes; and adding the resulting product to the microsphere dispersion with stirring, stirring for 1 hour to obtain a mixture 1;

[0127] 2) Sodium hyaluronate was added to the mixture 1 under stirring, and the mixture was stirred at room temperature for 2 hours, and allowed to stand for 12 hours to obtain a gel solution;

[0128] 3) Apply the gel on the surface of the drug carrier, and control the wet coating amount to 2.5g / cm 2 , and dried at 65°C for 4 h to obtain a dressing.

[0129] The sustained-release microspheres were prepared by the following method:

[0130] S1. Loading antibacterial carbon dots on mesoporous silica hollow spheres:

[0131] 2 g of mesoporous silica hollow spheres were added to 150 mL of deionized water and ultrasonically dispersed for 1 h. Then, 0.85 g of chitosan, 0.69 g of salicylic acid, 0.352 g of vitamin C, and 50 mL of ethanol were added and stirred for 45 min. The resulting mixture was transferred to a reactor and reacted at 180 ° C for 7 h. After filtration, the solid product was washed with deionized water and vacuum dried at 90 ° C for 12 h to obtain an antibacterial carrier.

[0132] S2. In situ deposition of silver nanoparticles on the antibacterial carrier:

[0133] Take 1 g of the antibacterial carrier and add it to 50 mL of 0.1 mol / L silver nitrate solution, ultrasonically disperse it for 30 minutes, and then add 5 wt% ammonia water to the obtained dispersion until the precipitate just disappears to obtain a mixture of the antibacterial carrier and silver ammonium solution. Add 10 mL of 0.5 mol / L glucose solution and 2 g of β-cyclodextrin to the mixture, react at 100°C for 30 minutes, filter, wash the solid product with ethanol and deionized water in turn, and vacuum dry at 80°C for 8 hours to obtain sustained-release microspheres.

[0134] Application performance testing:

[0135] Participants: 100 volunteers were selected from inpatients at the PLA General Hospital. The volunteers were aged 30-60 years, all had diabetes, had foot ulcer symptoms, and had a body mass index (BMI) of 20 to 32 kg / m 2 , including 50 males and 50 females.

[0136] 1. Analgesic effect test of dressing:

[0137] 1-1. Application method: After flushing the wound with 1% normal saline, apply the dressing to the wound, bandage and fix it with sterile gauze, and remove the dressing after leaving it for 2 hours.

[0138] 1-2. Effect evaluation method:

[0139] (1) The VAS pain score was used to quantify the pain scores of patients before and after application of the dressing to evaluate the pain relief effect of the dressing.

[0140] (2) The VAS pain rating scale, also known as the visual analogue scale, is a commonly used pain assessment tool for clinical patients. Scoring method: Draw a 10 cm horizontal line on a piece of paper, with one end of the line marked as 0, indicating no pain, and the other end as 10, indicating severe pain. The patient marks the corresponding position on the horizontal line according to the degree of pain they feel, and measures the distance from the starting point to the marked point. The resulting value is the pain score.

[0141] (3) Scoring criteria: 0 points for no pain; 1-3 points for mild pain, which the patient can tolerate and does not affect sleep; 4-6 points for moderate pain, which is obvious and affects sleep, but is still tolerable; 7-10 points for severe pain, which is severe and unbearable, seriously affecting sleep, and may be accompanied by symptoms such as sweating, dizziness, and fatigue. When using the VAS pain scoring scale, the researcher must first explain the scoring method to the patient to ensure that the patient understands and can accurately express the degree of pain. This method can more intuitively reflect the patient's pain perception and is a commonly used tool for visual scales to quantify pain intensity.

[0142] (4) Evaluation results: The pain score results before and after application are shown in Tables 1 and 2 below. It can be seen that the pain score was significantly reduced after using the dressing, indicating that the dressing has the effect of improving the pain of diabetic foot ulcers.

[0143] Table 1

[0144] VAS score / point Number of patients before medication Number of patients after administration 3 0 11 4 0 5 5 0 14 6 9 30 7 29 0 8 12 0 9 10 0

[0145] Table 2

[0146] Average VAS score Min (VAS score) Max (VAS score) Before spraying 7.38 6 9 After application 5.05 3 6

[0147] Note: Min and Max represent the minimum and maximum values ​​of VAS scores respectively.

[0148] 2. Promote wound healing performance

[0149] 2-1. Application Method: After rinsing the wound with 1% saline, apply a dressing to the wound and secure with sterile gauze. Leave it on for 5 days, then replace the dressing with a new one and apply the drug again. Repeat this process twice for a total of 10 days. Calculate the wound healing rate for each volunteer 10 days after application, and then calculate the average. Wound healing rate (%) = (original wound area - unhealed wound area) / original wound area.

[0150] The wound healing rate test results of Examples 1-3 and Comparative Examples 1-3 after 10 days of application are shown in Table 3 and Figure 3 As shown:

[0151] Table 3

[0152]

[0153] From the test results, it can be seen that in Example 2, the loading amount of Bletilla striata polysaccharide decreased, and the wound healing rate decreased slightly; in Comparative Example 1, Bletilla striata polysaccharide was directly added to the dressing, which had no sustained-release performance, and the wound healing rate decreased significantly; in Comparative Example 4, no Bletilla striata polysaccharide was added, and the wound healing rate decreased the most.

[0154] 3. Antibacterial performance test

[0155] The prepared dressings of each case were cut into round dressing samples with a diameter of 1 cm and sterilized by ultraviolet irradiation for 1 hour. 100 μL of Staphylococcus aureus suspension (concentration of 1×10 8 CFU / mL), the dressing samples were added to the culture medium and cultured at 37°C. The diameter of the inhibition zone (D) at 1 day and 10 days was recorded. Three parallel samples were collected in each group, and the average value was taken as the result. The test results are shown in Table 4 and Figure 4 As shown:

[0156] Table 4

[0157]

[0158] It can be seen from the test results that Examples 1-3 have long-lasting antibacterial properties, while the antibacterial properties of Comparative Examples 2 and 3 are significantly reduced.

[0159] Although the embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the description and implementation methods. They can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to specific details.

Claims

1. A dressing for promoting analgesia and regeneration of burn wounds, characterized in that: It includes a drug delivery carrier and a sustained-release multi-effect hydrogel loaded on the drug delivery carrier; The sustained-release multi-effect hydrogel comprises the following raw materials in parts by weight: 100 parts of water, 7-35 parts of multi-effect sustained-release microspheres, 3.5-10 parts of sodium carboxymethyl cellulose, 2.5-8 parts of sodium hyaluronate, and 0.5-4 parts of glycerol; The multi-effect sustained-release microspheres are prepared by the following method: S1, loading antibacterial carbon dots on mesoporous silica hollow spheres to obtain an antibacterial carrier; S2, in situ depositing silver nanoparticles on the antibacterial carrier to obtain a composite antibacterial carrier; S3. Bletilla striata polysaccharide is loaded on the composite antibacterial carrier by the impregnation method to obtain multi-effect sustained-release microspheres.

2. The dressing for promoting analgesia and regeneration of burn wounds according to claim 1, characterized in that: Step S1 is specifically as follows: Take the mesoporous silica hollow spheres and add them into deionized water, ultrasonically disperse them, then add chitosan, salicylic acid, vitamin C and ethanol, stir, transfer the obtained mixture into a reactor, react under heating, filter, wash and dry after the reaction is completed to obtain an antibacterial carrier.

3. The dressing for promoting analgesia and regeneration of burn wounds according to claim 2, characterized in that: Step S1 is specifically as follows: Take 1-4g of mesoporous silica hollow spheres and add them to 75-300mL of deionized water, ultrasonically disperse them for 0.5-2h, then add 0.42-1.7g of chitosan, 0.35-1.4g of salicylic acid, 0.15-0.7g of vitamin C, and 25-100mL of ethanol, stir for 30-90min, transfer the resulting mixture into a reactor, react at 160-200℃ for 3.5-10h, filter, wash the solid product with deionized water, and vacuum dry at 80-100℃ for 6-24h to obtain an antibacterial carrier.

4. The dressing for promoting analgesia and regeneration of burn wounds according to claim 1, characterized in that: Step S2 is specifically as follows: An antibacterial carrier is added to a silver nitrate solution and ultrasonically dispersed, and then ammonia water is added dropwise to the obtained dispersion until the precipitate just disappears to obtain a mixture of the antibacterial carrier and the silver ammonium solution. Glucose solution and β-cyclodextrin are added to the mixture, and the mixture is reacted under heating. After the reaction is completed, the mixture is filtered, washed, and dried to obtain a composite antibacterial carrier.

5. The dressing for promoting analgesia and regeneration of burn wounds according to claim 4, characterized in that: Step S2 is specifically as follows: Take 0.5-2g of the antibacterial carrier and add it to 25-100mL of a silver nitrate solution with a concentration of 0.05-0.2mol / L, ultrasonically disperse it for 15-60min, then add 2.5-10wt% ammonia water to the obtained dispersion until the precipitate just disappears to obtain a mixture of the antibacterial carrier and the silver ammonium solution, add 5-20mL of a glucose solution with a concentration of 0.25-1mol / L and 1-4g of β-cyclodextrin to the mixture, react at 90-110°C for 15-60min, filter, wash the solid product with ethanol and deionized water in sequence, and vacuum dry at 70-90°C for 4-12h to obtain a composite antibacterial carrier.

6. The dressing for promoting analgesia and regeneration of burn wounds according to claim 1, characterized in that: Step S3 is specifically as follows: The composite antibacterial carrier is added to deionized water and ultrasonically dispersed, and then Bletilla striata polysaccharide is added and stirred. The mixture is then sealed and shaken, and the seal is removed. The mixture is heated until the solvent is evaporated to dryness to obtain multi-effect sustained-release microspheres.

7. The dressing for promoting analgesia and regeneration of burn wounds according to claim 6, characterized in that: Step S3 is specifically as follows: Take 0.5-2g of the composite antibacterial carrier and add it to 25-100mL of deionized water, ultrasonically disperse it for 15-60min, then add 0.125-0.5g of Bletilla striata polysaccharide, stir it for 0.5-2h, then seal it, shake it on a shaker at 40-60℃ for 6-24h, remove the seal, and heat it at 90-100℃ until the solvent evaporates to obtain multi-effect sustained-release microspheres.

8. The dressing for promoting analgesia and regeneration of burn wounds according to claim 1, characterized in that: The multi-effect sustained-release microspheres are prepared by the following method: S1. Loading antibacterial carbon dots on mesoporous silica hollow spheres: 2 g of mesoporous silica hollow spheres were added to 150 mL of deionized water and ultrasonically dispersed for 1 h. Then, 0.85 g of chitosan, 0.69 g of salicylic acid, 0.352 g of vitamin C, and 50 mL of ethanol were added and stirred for 45 min. The resulting mixture was transferred to a reactor and reacted at 180 ° C for 7 h. After filtration, the solid product was washed with deionized water and vacuum dried at 90 ° C for 12 h to obtain an antibacterial carrier. S2. In situ deposition of silver nanoparticles on the antibacterial carrier: 1 g of the antibacterial carrier was added to 50 mL of a 0.1 mol / L silver nitrate solution and ultrasonically dispersed for 30 minutes. Then, 5 wt% ammonia water was added dropwise to the resulting dispersion until the precipitate just disappeared to obtain a mixture of the antibacterial carrier and the silver ammonium solution. 10 mL of a 0.5 mol / L glucose solution and 2 g of β-cyclodextrin were added to the mixture, and the mixture was reacted at 100°C for 30 minutes. The mixture was filtered, and the solid product was washed with ethanol and deionized water in sequence, and vacuum dried at 80°C for 8 hours to obtain a composite antibacterial carrier. S3. Loading Bletilla striata polysaccharide on the composite antibacterial carrier by impregnation method: Take 1g of the composite antibacterial carrier and add it to 50mL of deionized water, ultrasonically disperse it for 30min, then add 0.25g of Bletilla striata polysaccharide and stir it for 1h. Then seal it and shake it on a shaker at 50℃ for 12h. Unseal it and heat it at 100℃ until the solvent evaporates to obtain multi-effect sustained-release microspheres.

9. A method for preparing a dressing for promoting analgesia and regeneration of burn wounds according to any one of claims 1 to 8, characterized in that: The following steps are involved: 1) adding multi-effect sustained-release microspheres to a portion of deionized water and ultrasonically dispersing the microspheres to obtain a microsphere dispersion; adding sodium carboxymethyl cellulose and glycerol to the remaining deionized water and stirring; and adding the resulting product to the microsphere dispersion while stirring to obtain a mixture 1; 2) adding sodium hyaluronate to the mixture 1 under stirring, stirring and reacting at room temperature, and allowing to stand to obtain a gel solution; 3) The gel is coated on the surface of the drug delivery carrier and dried to obtain a dressing.

10. The method for preparing the dressing for promoting analgesia and regeneration of burn wounds according to claim 9, characterized in that: The following steps are involved: 1) adding multi-effect sustained-release microspheres to 3 / 4 of the total mass of deionized water and ultrasonically dispersing the microspheres for 30-60 minutes to obtain a microsphere dispersion; adding sodium carboxymethyl cellulose and glycerol to the remaining deionized water and stirring for 5-30 minutes; and adding the resulting product to the microsphere dispersion with stirring, stirring for 0.5-2 hours to obtain a mixture 1; 2) adding sodium hyaluronate to mixture 1 under stirring, reacting at room temperature for 1-4 hours, and allowing to stand for 6-24 hours to obtain a gel solution; 3) Apply the gel to the surface of the drug carrier, and control the wet coating amount to 1.5-5g / cm 2 , and dried at 60-70°C for 2-8h to obtain a dressing.

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