Microcapsule controlled-release medical dressing and preparation method thereof

Abstract

The invention relates to the technical field of medical supplies, and discloses a microcapsule controlled-release medical dressing and a preparation method thereof.The microcapsule controlled-release medical dressing comprises a base cloth layer, a microcapsule layer arranged on one side of the base cloth layer and a protective layer covering the microcapsule layer; the microcapsule layer is composed of a plurality of drug-loaded microcapsules, each microcapsule is composed of a wall material and a core material, the core material is a wound treatment drug, and the wall material is a modified chitosan-sodium alginate composite wall material; the base cloth layer is a polyurethane non-woven fabric with air holes, and the protective layer is a degradable hyaluronic acid film. The microcapsule is suitable for various types of wounds, such as surgical incisions, burn wounds, chronic ulcers and the like, different wound treatment requirements can be met by adjusting the types of antibiotics in the microcapsule, the crosslinking degree of the wall materials and the drug loading capacity, and the microcapsule has a wide clinical application prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of medical supplies, in particular to a microcapsule controlled-release medical dressing and a preparation method thereof. Background Art

[0002] Medical dressings play a vital role in wound care. Their primary functions include protecting wounds from external contaminants, absorbing wound exudate, and providing a moist environment conducive to wound healing. Traditional medical dressings are mostly simply physical barriers, unable to effectively deliver drugs or maintain their effects. With the advancement of medicine, medical dressings with sustained-release drug functionality have become a research hotspot. Although some drug-loaded medical dressings have been developed, they still face numerous challenges in practical application. For example, the drug release rate is difficult to precisely control, which can result in excessively rapid release, preventing effective drug concentrations from being maintained at the wound site, or excessively slow release, preventing the timely therapeutic effect. Therefore, developing a medical dressing that can precisely control drug release rates while exhibiting excellent biocompatibility and wound adaptability is of great practical significance. Summary of the Invention

[0003] (1) Technical problems solved In view of the deficiencies of the prior art, the present invention provides a microcapsule controlled-release medical dressing and a preparation method thereof.

[0004] (2) Technical solution To achieve the above-mentioned object, the present invention provides the following technical solution: a microcapsule controlled-release medical dressing, characterized in that it comprises a base fabric layer, a microcapsule layer arranged on one side of the base fabric layer, and a protective layer covering the microcapsule layer; The microcapsule layer is composed of multiple drug-loaded microcapsules, and the microcapsules are composed of wall material and core material. The core material is a drug for treating wounds, and the wall material is a modified chitosan-sodium alginate composite wall material; the base fabric layer is a polyurethane non-woven fabric with air permeability, and the protective layer is a degradable hyaluronic acid film.

[0005] Furthermore, the medicine for treating the wound is one of antibiotics, growth factors, and analgesics.

[0006] Furthermore, the preparation method of the microcapsules comprises the following steps: A1. Add 20-40 parts of modified chitosan to 800-1000 parts of 1% acetic acid aqueous solution, stir at 150-200 rpm for 10-15 min in a 40-60°C water bath to prepare a modified chitosan solution, and adjust the pH to 5.5-6. A2. Disperse 60-80 parts of calcium alginate-drug gel microspheres in a modified chitosan solution, stir at 20-40°C and 100-150 r / min for 10-20 min, slowly add dropwise 80-100 parts of a 0.1% by mass genipin solution in a 50% ethanol aqueous solution as solvent, and continue the reaction for 1-2 h. After the reaction is completed, centrifuge at 5000-8000 r / min for 10-20 min, collect the microcapsules, wash them with 50% ethanol aqueous solution and deionized water in sequence, freeze-dry, and pre-freeze at -50°C for 2-4 h with a vacuum degree of <20 Pa to obtain microcapsules.

[0007] Furthermore, the preparation method of modified chitosan comprises the following steps: B1. Weigh 60-80 parts of chitosan and dissolve it in a 1-3% acetic acid solution. Stir at 150-250 rpm at 30-50°C for 15-30 min to prepare a chitosan solution with a mass concentration of 1-3%. Add 0.5-1.5% nanohydroxyapatite particles and ultrasonically disperse the solution for 20-30 min at a frequency of 40-60 kHz. Set aside. B2, dissolving 100-150 parts of dimethylaminoethyl methacrylate monomer and 0.5-1.5 parts of initiator azobisisobutyronitrile in 1000-1500 parts of anhydrous ethanol, deoxygenating with nitrogen for 10-30 minutes, stirring and reacting at 50-70°C for 2-6 hours. After the reaction is completed, pouring the product into icy ether for precipitation, and vacuum drying to obtain polydimethylaminoethyl methacrylate; B3. Polydimethylaminoethyl methacrylate was dissolved in 100-150 parts of N,N-dimethylformamide to prepare a polydimethylaminoethyl methacrylate solution. The chitosan solution and the polydimethylaminoethyl methacrylate solution were mixed in a volume ratio of 10:1. 2-5 parts of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1-3 parts of N-hydroxysuccinimide were added as cross-linking agents. The mixture was stirred at pH 5.5-6.5 and 25-30°C for 4-6 h. After the reaction, the mixture was dialyzed and purified using a dialysis bag with a molecular weight cutoff of 8000-14000 Da. The modified chitosan was then freeze-dried to obtain the product.

[0008] Furthermore, the preparation method of calcium alginate-drug gel microspheres comprises the following steps: C1. Hydrophilic drugs: Dissolve directly in MES buffer (pH 6.0) at a concentration of 10 mg / mL and add 0.5% trehalose as a stabilizer to prepare a solution. Hydrophobic drugs: Disperse in anhydrous ethanol containing 1% Tween 80 and ultrasonicate at 200-300 W for 5-10 min. Then, slowly add dropwise to deionized water at a water:ethanol mass ratio of 6-9:1 to form a suspension. C2. Weigh sodium alginate and add it to deionized water. Stir at room temperature at 100-200 r / min for 10-15 min to prepare a sodium alginate solution with a mass concentration of 1-3%. Slowly add the drug solution or suspension to the sodium alginate solution and stir at 25-35°C for 10-20 min to obtain a mixed solution. C3. Under stirring conditions, add the prepared mixed solution dropwise into the calcium chloride solution. The mass concentration of the calcium chloride solution is 2-5%. The dropwise addition rate is controlled at 1-3 mL / min to form calcium alginate-drug gel microspheres.

[0009] Furthermore, the particle size of the microcapsules is 5~20 μm, and the encapsulation efficiency is ≥85%.

[0010] Furthermore, the preparation method of the microcapsule layer includes the following steps: dispersing the prepared microcapsules in deionized water to prepare a microcapsule suspension with a mass concentration of 5-10%, then uniformly coating the microcapsule suspension on one side of the base fabric layer, and fixing the microcapsules on the base fabric layer by hot air drying to form a microcapsule layer.

[0011] Furthermore, the preparation method of the protective layer includes the following steps: dissolving hyaluronic acid in deionized water to prepare a hyaluronic acid solution with a mass concentration of 2-5%, and then evenly coating the hyaluronic acid solution on the microcapsule layer, and naturally drying it at room temperature to form a hyaluronic acid film, i.e., the protective layer.

[0012] (3) Beneficial technical effects The medical dressing of the present invention uses modified chitosan-sodium alginate composite wall material to prepare microcapsules, and achieves precise controlled release of antibiotics through a double cross-linking process and intelligent grafting technology. Modified chitosan grafted with polydimethylaminoethyl methacrylate promotes the expansion of the wall material network, accelerates the release of antibiotics, and quickly inhibits bacterial growth; while in the neutral environment of normal tissue, the drug release rate is significantly reduced, reducing systemic toxicity and improving drug utilization efficiency. The double-layer cross-linking process of calcium alginate-drug gel microspheres and modified chitosan effectively reduces drug loss during the preparation process, ensures that more antibiotics are encapsulated in the microcapsules, and provides sufficient drug reserves for continuous antibacterial treatment.

[0013] By optimizing the preparation process and modifying the materials, this invention further reduces cytotoxicity, resulting in a significantly higher cell survival rate than traditional dressings. Furthermore, the hyaluronic acid protective layer promotes cell adhesion and proliferation, accelerating wound healing. The nanohydroxyapatite in the modified wall material also induces tissue regeneration, creating a favorable microenvironment for wound repair. The present invention is suitable for various types of wounds, such as surgical incisions, burn wounds, chronic ulcers, etc. By adjusting the type of antibiotics in the microcapsules, the degree of wall material cross-linking and the drug loading, it can meet the treatment needs of different wounds and has broad clinical application prospects. DETAILED DESCRIPTION

[0014] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts shall fall within the scope of protection of the present invention.

[0015] The components of the microcapsule controlled-release medical dressing formula of the present invention are commercially available unless otherwise specified. The parts used in the present invention are all parts by weight; Example 1, a microcapsule controlled-release medical dressing, comprising a base fabric layer, a microcapsule layer disposed on one side of the base fabric layer, and a protective layer covering the microcapsule layer; The microcapsule layer is composed of multiple drug-loaded microcapsules, and the microcapsules are composed of wall material and core material. The core material is a drug for treating wounds, and the wall material is a modified chitosan-sodium alginate composite wall material; the base fabric layer is a polyurethane non-woven fabric with air permeability, and the protective layer is a degradable hyaluronic acid film.

[0016] The medicine used to treat the wound is antibiotics.

[0017] The particle size of the microcapsules is 5~20 μm, and the encapsulation efficiency is ≥85%.

[0018] The preparation method of the microcapsule layer includes the following steps: dispersing the prepared microcapsules in deionized water to prepare a microcapsule suspension with a mass concentration of 5%, then uniformly coating the microcapsule suspension on one side of the base fabric layer, and fixing the microcapsules on the base fabric layer by hot air drying to form a microcapsule layer.

[0019] The preparation method of the protective layer includes the following steps: dissolving hyaluronic acid in deionized water to prepare a hyaluronic acid solution with a mass concentration of 2%, then evenly coating the hyaluronic acid solution on the microcapsule layer, and naturally drying it at room temperature to form a hyaluronic acid film, i.e., the protective layer.

[0020] The preparation method of microcapsules comprises the following steps: A1. Add 20 parts of modified chitosan to 800 parts of 1% acetic acid aqueous solution, stir at 150 rpm for 10 min in a 40°C water bath to prepare a modified chitosan solution, and adjust the pH to 5.5. A2. Disperse 60 parts of calcium alginate-drug gel microspheres in modified chitosan solution, stir at 20°C and 100 r / min for 10 min, slowly add 80 parts of 0.1% genipin solution (solvent: 50% ethanol aqueous solution) into the system, and continue the reaction for 1 h. After the reaction is completed, centrifuge at 5000 r / min for 10 min, collect the microcapsules, wash them with 50% ethanol aqueous solution and deionized water in sequence, freeze-dry, and pre-freeze at -50°C for 2 h with a vacuum degree of <20 Pa to obtain microcapsules.

[0021] The preparation method of modified chitosan comprises the following steps: B1. Weigh 60 parts of chitosan and dissolve it in 1% acetic acid solution. Stir at 150 rpm for 15 min at 30°C to prepare a 1% chitosan solution. Add 0.5% nano-hydroxyapatite particles and ultrasonically disperse the solution for 20 min at a frequency of 40 kHz. Set aside. B2, dissolving 100 parts of dimethylaminoethyl methacrylate monomer and 0.5 parts of initiator azobisisobutyronitrile in 1000 parts of anhydrous ethanol, deoxygenating with nitrogen for 10 minutes, and stirring at 50°C for 2 hours. After the reaction, the product was poured into icy ether for precipitation and vacuum dried to obtain polydimethylaminoethyl methacrylate; B3. Polydimethylaminoethyl methacrylate was dissolved in 100 parts of N,N-dimethylformamide to prepare a polydimethylaminoethyl methacrylate solution. The chitosan solution and the polydimethylaminoethyl methacrylate solution were mixed in a volume ratio of 10:1. 2 parts of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1 part of N-hydroxysuccinimide were added as cross-linking agents. The mixture was stirred at pH 5.5 and 25°C for 4 h. After the reaction, the mixture was dialyzed and purified with a dialysis bag with a molecular weight cutoff of 8000 Da. The modified chitosan was then freeze-dried to obtain the product.

[0022] The preparation method of calcium alginate-drug gel microspheres comprises the following steps: C1. Hydrophilic drugs: directly dissolved in MES buffer (pH 6.0) at a concentration of 10 mg / mL, and 0.5% trehalose was added as a stabilizer to prepare a solution. Hydrophobic drugs: first dispersed in anhydrous ethanol containing 1% Tween 80, ultrasonically treated at 200 W for 5 minutes, and then slowly added dropwise to deionized water at a water:ethanol mass ratio of 6:1 to form a suspension. C2. Weigh sodium alginate and add it to deionized water. Stir the mixture at 100 rpm for 10 minutes at room temperature to prepare a sodium alginate solution with a mass concentration of 1%. Slowly add the drug solution or suspension to the sodium alginate solution and stir at 25°C for 10 minutes to obtain a mixed solution. C3. Under stirring conditions, add the prepared mixed solution dropwise into the calcium chloride solution. The mass concentration of the calcium chloride solution is 2%, and the dropping speed is controlled at 1 mL / min to form calcium alginate-drug gel microspheres.

[0023] Example 2, a microcapsule controlled-release medical dressing, comprising a base fabric layer, a microcapsule layer disposed on one side of the base fabric layer, and a protective layer covering the microcapsule layer; The microcapsule layer is composed of multiple drug-loaded microcapsules, and the microcapsules are composed of wall material and core material. The core material is a drug for treating wounds, and the wall material is a modified chitosan-sodium alginate composite wall material; the base fabric layer is a polyurethane non-woven fabric with air permeability, and the protective layer is a degradable hyaluronic acid film.

[0024] The medicine used to treat the wound is antibiotics.

[0025] The particle size of the microcapsules is 5~20 μm, and the encapsulation efficiency is ≥85%.

[0026] The preparation method of the microcapsule layer includes the following steps: dispersing the prepared microcapsules in deionized water to prepare a microcapsule suspension with a mass concentration of 8%, then uniformly coating the microcapsule suspension on one side of the base fabric layer, and fixing the microcapsules on the base fabric layer by hot air drying to form a microcapsule layer.

[0027] The preparation method of the protective layer includes the following steps: dissolving hyaluronic acid in deionized water to prepare a hyaluronic acid solution with a mass concentration of 8%, then evenly coating the hyaluronic acid solution on the microcapsule layer, and naturally drying it at room temperature to form a hyaluronic acid film, i.e., the protective layer.

[0028] The preparation method of microcapsules comprises the following steps: A1. Add 30 parts of modified chitosan to 900 parts of 1% acetic acid aqueous solution, stir at 180 rpm for 10 min in a 50°C water bath to prepare a modified chitosan solution, and adjust the pH to 5.5. A2. Disperse 70 parts of calcium alginate-drug gel microspheres in modified chitosan solution, stir at 30°C and 120 r / min for 15 min, slowly add 90 parts of 0.1% genipin solution by mass into the system, the solvent is 50% ethanol aqueous solution, and continue the reaction for 1.5 h. After the reaction is completed, centrifuge at 6000 r / min for 15 min, collect the microcapsules, wash them with 50% ethanol aqueous solution and deionized water in sequence, freeze-dry, and pre-freeze at -50°C for 3 h with a vacuum degree of <20 Pa to obtain microcapsules.

[0029] The preparation method of modified chitosan comprises the following steps: B1. Weigh 70 parts of chitosan and dissolve it in 2% acetic acid solution. Stir at 200 r / min at 40°C for 20 min to prepare a 2% chitosan solution. Add 1% nano-hydroxyapatite particles and perform ultrasonic dispersion for 20 min at a frequency of 50 kHz. Set aside. B2, dissolving 120 parts of dimethylaminoethyl methacrylate monomer and 1 part of initiator azobisisobutyronitrile in 1200 parts of anhydrous ethanol, deoxygenating with nitrogen for 20 minutes, and stirring at 60°C for 4 hours. After the reaction, the product was poured into icy ether for precipitation and vacuum dried to obtain polydimethylaminoethyl methacrylate; B3. Polydimethylaminoethyl methacrylate was dissolved in 120 parts of N,N-dimethylformamide to prepare a polydimethylaminoethyl methacrylate solution. The chitosan solution and the polydimethylaminoethyl methacrylate solution were mixed in a volume ratio of 10:1. 3 parts of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 2 parts of N-hydroxysuccinimide were added as cross-linking agents. The mixture was stirred at pH 6 and 28°C for 5 h. After the reaction, the mixture was dialyzed and purified using a dialysis bag with a molecular weight cutoff of 10,000 Da, and freeze-dried to obtain modified chitosan.

[0030] The preparation method of calcium alginate-drug gel microspheres comprises the following steps: C1. Hydrophilic drugs: Dissolve directly in MES buffer (pH 6.0) at a concentration of 10 mg / mL, and add 0.5% trehalose as a stabilizer to prepare a solution. Hydrophobic drugs: Disperse in anhydrous ethanol containing 1% Tween 80, ultrasonically treat at 250 W for 5 minutes, and then slowly add dropwise to deionized water at a water:ethanol ratio of 7:1 to form a suspension. C2. Weigh sodium alginate and add it to deionized water. Stir at room temperature at 150 r / min for 10 min to prepare a sodium alginate solution with a mass concentration of 2%. Slowly add the drug solution or suspension to the sodium alginate solution and stir at 30°C for 15 min to obtain a mixed solution. C3. Under stirring conditions, add the prepared mixed solution dropwise into the calcium chloride solution. The mass concentration of the calcium chloride solution is 3% and the dropping speed is controlled at 2 mL / min to form calcium alginate-drug gel microspheres.

[0031] Example 3, a microcapsule controlled-release medical dressing, comprising a base fabric layer, a microcapsule layer disposed on one side of the base fabric layer, and a protective layer covering the microcapsule layer; The microcapsule layer is composed of multiple drug-loaded microcapsules, and the microcapsules are composed of wall material and core material. The core material is a drug for treating wounds, and the wall material is a modified chitosan-sodium alginate composite wall material; the base fabric layer is a polyurethane non-woven fabric with air permeability, and the protective layer is a degradable hyaluronic acid film.

[0032] The medicine used to treat the wound is antibiotics.

[0033] The particle size of the microcapsules is 5~20 μm, and the encapsulation efficiency is ≥85%.

[0034] The preparation method of the microcapsule layer includes the following steps: dispersing the prepared microcapsules in deionized water to prepare a microcapsule suspension with a mass concentration of 10%, then uniformly coating the microcapsule suspension on one side of the base fabric layer, and fixing the microcapsules on the base fabric layer by hot air drying to form a microcapsule layer.

[0035] The preparation method of the protective layer includes the following steps: dissolving hyaluronic acid in deionized water to prepare a hyaluronic acid solution with a mass concentration of 5%, then evenly coating the hyaluronic acid solution on the microcapsule layer, and naturally drying it at room temperature to form a hyaluronic acid film, i.e., the protective layer.

[0036] The preparation method of microcapsules comprises the following steps: A1. Add 40 parts of modified chitosan to 1000 parts of 1% acetic acid aqueous solution, stir at 200 rpm for 15 min in a 60°C water bath to prepare a modified chitosan solution, and adjust the pH to 6. A2. Disperse 80 parts of calcium alginate-drug gel microspheres in modified chitosan solution, stir at 40°C and 150 r / min for 20 min, slowly add 100 parts of 0.1% genipin solution (solvent: 50% ethanol aqueous solution) dropwise into the system, and continue the reaction for 2 h. After the reaction is completed, centrifuge at 8000 r / min for 20 min, collect the microcapsules, wash them with 50% ethanol aqueous solution and deionized water in sequence, freeze-dry, and pre-freeze at -50°C for 4 h with a vacuum degree of <20 Pa to obtain microcapsules.

[0037] The preparation method of modified chitosan comprises the following steps: B1. Weigh 80 parts of chitosan and dissolve it in 3% acetic acid solution. Stir at 250 rpm and 50°C for 30 min to prepare a 3% chitosan solution. Add 1.5% nano-hydroxyapatite particles and perform ultrasonic dispersion for 30 min at a frequency of 60 kHz. Set aside. B2, dissolving 150 parts of dimethylaminoethyl methacrylate monomer and 1.5 parts of initiator azobisisobutyronitrile in 1500 parts of anhydrous ethanol, deoxygenating with nitrogen for 30 minutes, and stirring at 70°C for 6 hours. After the reaction, the product was poured into icy ether for precipitation and vacuum dried to obtain polydimethylaminoethyl methacrylate; B3. Polydimethylaminoethyl methacrylate was dissolved in 150 parts of N,N-dimethylformamide to prepare a polydimethylaminoethyl methacrylate solution. The chitosan solution and the polydimethylaminoethyl methacrylate solution were mixed in a volume ratio of 10:1. 5 parts of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 3 parts of N-hydroxysuccinimide were added as cross-linking agents. The mixture was stirred at pH 6.5 and 30°C for 4-6 h. After the reaction, the mixture was dialyzed and purified using a dialysis bag with a molecular weight cutoff of 14,000 Da. The modified chitosan was then freeze-dried to obtain the product.

[0038] The preparation method of calcium alginate-drug gel microspheres comprises the following steps: C1. Hydrophilic drugs: Dissolve directly in MES buffer (pH 6.0) at a concentration of 10 mg / mL, and add 0.5% trehalose as a stabilizer to prepare a solution. Hydrophobic drugs: Disperse in anhydrous ethanol containing 1% Tween 80, ultrasonically treat at 300 W for 10 min, and then slowly add dropwise to deionized water at a water:ethanol mass ratio of 9:1 to form a suspension. C2. Weigh sodium alginate and add it to deionized water. Stir at 200 r / min at room temperature for 15 minutes to prepare a sodium alginate solution with a mass concentration of 3%. Slowly add the drug solution or suspension to the sodium alginate solution and stir at 35°C for 20 minutes to obtain a mixed solution. C3. Under stirring conditions, add the prepared mixed solution dropwise into the calcium chloride solution. The mass concentration of the calcium chloride solution is 5%, and the dropping speed is controlled at 3 mL / min to form calcium alginate-drug gel microspheres.

[0039] Comparative Example 1: Unmodified chitosan, the rest of the process is the same as Example 1.

[0040] Comparative Example 2: The microcapsule wall material is single sodium alginate, and the rest of the process is the same as Example 1.

[0041] Comparative Example 3: The microcapsule wall material is ordinary chitosan-sodium alginate composite wall material, and no nano-hydroxyapatite is added. The rest of the process is the same as in Example 1.

[0042] Test example: 1. Drug encapsulation efficiency test Using high-performance liquid chromatography (HPLC), accurately weigh a microcapsule sample and add an appropriate amount of a demulsifier (e.g., ethanol) to dissolve the microcapsule wall material and release the drug. Centrifuge the solution (8000 rpm for 15 minutes) and collect the supernatant for HPLC analysis.

[0043] 2. Controlled release performance test Release experiments were conducted by placing the microcapsules in simulated body fluid (PBS buffer, pH 7.4) at 37°C with constant shaking (100 rpm). 5 mL samples were taken at 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h, and an equal volume of fresh PBS buffer was added. High-performance liquid chromatography was used to determine drug concentrations in the samples, and cumulative release curves were plotted to analyze the release rate and release pattern.

[0044] 3. Biocompatibility testing The cytotoxicity was detected by MTT assay. L929 mouse fibroblasts were cultured at 1×10 4The cells were seeded at a density of 100 cells / well in a 96-well plate. After 24 hours of culture, the extracts of the different samples were added (the dressing samples were soaked in DMEM medium at a ratio of 1 g / mL and shaken at 37°C for 24 hours, and the supernatant was used as the extract). A blank control group (DMEM medium alone) and a positive control group (DMEM medium supplemented with 0.1% Triton X-100) were also set up. After another 24 hours of culture, 20 μL of MTT solution (5 mg / mL) was added to each well and incubated at 37°C for 4 hours. The supernatant was discarded, and 150 μL of dimethyl sulfoxide (DMSO) was added. The cells were shaken for 10 minutes to fully dissolve the formazan. The absorbance (OD) was measured at 570 nm using a microplate reader.

[0045] Table 1 Drug encapsulation efficiency test results

[0046] Table 2 Controlled release performance test results

[0047] Table 3 Biocompatibility test results

[0048] As can be seen from the table, the examples are superior to the comparative examples in terms of drug encapsulation efficiency, controlled release performance and biocompatibility, fully demonstrating the technical advantages of using modified chitosan-sodium alginate composite wall materials and optimizing the preparation process, and providing a better solution for the development of microcapsule controlled-release medical dressings.

[0049] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A microcapsule controlled-release medical dressing, characterized in that: It comprises a base fabric layer, a microcapsule layer arranged on one side of the base fabric layer, and a protective layer covering the microcapsule layer; The microcapsule layer is composed of a plurality of drug-loaded microcapsules, each of which is composed of a wall material and a core material. The core material is a wound-treating drug, and the wall material is a modified chitosan-sodium alginate composite wall material. The base fabric layer is a polyurethane non-woven fabric with air permeability, and the protective layer is a degradable hyaluronic acid film. The preparation method of modified chitosan comprises the following steps: B1. Weigh 60-80 parts of chitosan and dissolve it in a 1-3% acetic acid solution. Stir at 150-250 rpm at 30-50°C for 15-30 min to prepare a chitosan solution with a mass concentration of 1-3%. Add 0.5-1.5% nanohydroxyapatite particles and ultrasonically disperse the solution for 20-30 min at a frequency of 40-60 kHz. Set aside. B2, dissolving 100-150 parts of dimethylaminoethyl methacrylate monomer and 0.5-1.5 parts of initiator azobisisobutyronitrile in 1000-1500 parts of anhydrous ethanol, deoxygenating with nitrogen for 10-30 minutes, stirring and reacting at 50-70°C for 2-6 hours. After the reaction is completed, pouring the product into icy ether for precipitation, and vacuum drying to obtain polydimethylaminoethyl methacrylate; B3. Polydimethylaminoethyl methacrylate was dissolved in 100-150 parts of N,N-dimethylformamide to prepare a polydimethylaminoethyl methacrylate solution. The chitosan solution and the polydimethylaminoethyl methacrylate solution were mixed in a volume ratio of 10:

1. 2-5 parts of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1-3 parts of N-hydroxysuccinimide were added as cross-linking agents. The mixture was stirred at pH 5.5-6.5 and 25-30°C for 4-6 h. After the reaction, the mixture was dialyzed and purified using a dialysis bag with a molecular weight cutoff of 8000-14000 Da. The modified chitosan was then freeze-dried to obtain the product.

2. The microcapsule controlled-release medical dressing according to claim 1, characterized in that: The medicine used to treat the wound is one of antibiotics, growth factors, and analgesics.

3. The microcapsule controlled-release medical dressing according to claim 1, characterized in that: The preparation method of microcapsules comprises the following steps: A1. Add 20-40 parts of modified chitosan to 800-1000 parts of 1% acetic acid aqueous solution, stir at 150-200 rpm for 10-15 min in a 40-60°C water bath to prepare a modified chitosan solution, and adjust the pH to 5.5-6. A2. Disperse 60-80 parts of calcium alginate-drug gel microspheres in a modified chitosan solution, stir at 20-40°C and 100-150 r / min for 10-20 min, slowly add dropwise 80-100 parts of a 0.1% by mass genipin solution in a 50% ethanol aqueous solution as solvent, and continue the reaction for 1-2 h. After the reaction is completed, centrifuge at 5000-8000 r / min for 10-20 min, collect the microcapsules, wash them with 50% ethanol aqueous solution and deionized water in sequence, freeze-dry, and pre-freeze at -50°C for 2-4 h with a vacuum degree of <20 Pa to obtain microcapsules.

4. The microcapsule controlled-release medical dressing according to claim 3, characterized in that: The preparation method of calcium alginate-drug gel microspheres comprises the following steps: C1. Hydrophilic drugs: Dissolve directly in MES buffer (pH 6.0) at a concentration of 10 mg / mL and add 0.5% trehalose as a stabilizer to prepare a solution. Hydrophobic drugs: Disperse in anhydrous ethanol containing 1% Tween 80 and ultrasonicate at 200-300 W for 5-10 min. Then, slowly add dropwise to deionized water at a water:ethanol mass ratio of 6-9:1 to form a suspension. C2. Weigh sodium alginate and add it to deionized water. Stir at room temperature at 100-200 r / min for 10-15 min to prepare a sodium alginate solution with a mass concentration of 1-3%. Slowly add the drug solution or suspension to the sodium alginate solution and stir at 25-35°C for 10-20 min to obtain a mixed solution. C3. Under stirring conditions, add the prepared mixed solution dropwise into the calcium chloride solution. The mass concentration of the calcium chloride solution is 2-5%. The dropwise addition rate is controlled at 1-3 mL / min to form calcium alginate-drug gel microspheres.

5. The microcapsule controlled-release medical dressing according to claim 3, characterized in that: The particle size of the microcapsules is 5~20μm, and the encapsulation efficiency is ≥85%.

6. The microcapsule controlled-release medical dressing according to claim 1, characterized in that: The preparation method of the microcapsule layer includes the following steps: dispersing the prepared microcapsules in deionized water to prepare a microcapsule suspension with a mass concentration of 5-10%, then uniformly coating the microcapsule suspension on one side of the base fabric layer, and fixing the microcapsules on the base fabric layer by hot air drying to form a microcapsule layer.

7. The microcapsule controlled-release medical dressing according to claim 1, characterized in that: The preparation method of the protective layer includes the following steps: dissolving hyaluronic acid in deionized water to prepare a hyaluronic acid solution with a mass concentration of 2-5%, then evenly coating the hyaluronic acid solution on the microcapsule layer, and naturally drying it at room temperature to form a hyaluronic acid film, i.e., the protective layer.

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