A microcapsule controlled release medical dressing and a method of making the same

Abstract

The application relates to the technical field of medical supplies, and discloses a microcapsule controlled-release medical dressing and a preparation method thereof, which 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; the microcapsule is composed of a wall material and a core material; the core material is a drug for treating a wound; 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 permeable holes; and the protective layer is a degradable hyaluronic acid film. The application is suitable for various types of wounds, such as surgical incisions, burn wounds, chronic ulcers and the like; by adjusting the types of antibiotics in the microcapsules, the crosslinking degree of the wall material and the drug loading capacity, the treatment requirements of different wounds can be met, and the application has a wide clinical application prospect.

Description

Technical Field

[0001] This invention relates to the field of medical supplies technology, specifically to a microcapsule controlled-release medical dressing and its preparation method. Background Technology

[0002] Medical dressings play a crucial role in wound care, with their main functions including protecting wounds from external contamination, absorbing wound exudate, and providing a moist environment conducive to wound healing. Traditional medical dressings are mostly just simple physical barriers, unable to effectively deliver and sustain medication. With advancements in medicine, medical dressings with sustained-release drug functions have gradually become a research hotspot.

[0003] Currently, although some drug-loaded medical dressings have been developed, many problems still exist in practical applications. For example, the drug release rate is difficult to control precisely, which may result in the drug being released too quickly, failing to maintain an effective drug concentration at the wound site; or the drug being released too slowly, failing to exert its therapeutic effect in a timely manner. Therefore, developing a medical dressing that can precisely control the drug release rate and has good biocompatibility and wound adaptability is of great practical significance. Summary of the Invention

[0004] (a) Technical problems to be solved

[0005] To address the shortcomings of existing technologies, this invention provides a microcapsule controlled-release medical dressing and its preparation method.

[0006] (II) Technical Solution

[0007] To achieve the above objectives, 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 disposed on one side of the base fabric layer, and a protective layer covering the microcapsule layer;

[0008] The microcapsule layer consists of multiple drug-loaded microcapsules, each microcapsule consisting of a wall material and a 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 nonwoven fabric with breathable pores, and the protective layer is a biodegradable hyaluronic acid film.

[0009] Furthermore, the medication used to treat the wound is one of the following: antibiotics, growth factors, or analgesics.

[0010] Furthermore, the method for preparing microcapsules includes the following steps:

[0011] A1. Add 20-40 parts of modified chitosan to 800-1000 parts of 1% acetic acid aqueous solution, stir at 150-200 r / min for 10-15 min under water bath conditions of 40-60℃ to prepare modified chitosan solution, and adjust the pH to 5.5-6.

[0012] A2. Disperse 60-80 parts of calcium alginate-drug gel microspheres in a modified chitosan solution, stir for 10-20 min at 20-40℃ and 100-150 r / min, slowly add 80-100 parts of 0.1% genipin solution (50% ethanol aqueous solution) to the system, 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 sequentially with 50% ethanol aqueous solution and deionized water, freeze-dry, pre-freeze at -50℃ for 2-4 h under vacuum <20 Pa to obtain the microcapsules.

[0013] Furthermore, the preparation method of modified chitosan includes the following steps:

[0014] B1. Weigh 60-80 parts of chitosan and dissolve it in a 1-3% acetic acid solution. Stir at 150-250 r / min for 15-30 min at 30-50℃ to prepare a 1-3% chitosan solution. Add 0.5-1.5% nano-hydroxyapatite particles and ultrasonically disperse for 20-30 min at a frequency of 40-60 kHz.

[0015] B2. Dissolve 100-150 parts of dimethylaminoethyl methacrylate monomer and 0.5-1.5 parts of initiator azobisisobutyronitrile in 1000-1500 parts of anhydrous ethanol. After purging with nitrogen for 10-30 min, stir the reaction at 50-70℃ for 2-6 h. After the reaction is complete, pour the product into ice-cold ether to precipitate it, and dry it under vacuum to obtain polydimethylaminoethyl methacrylate.

[0016] B3. Poly(dimethylaminoethyl methacrylate) solution was prepared by dissolving 100-150 parts of N,N-dimethylformamide. Chitosan solution and poly(dimethylaminoethyl methacrylate) solution were mixed at 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 crosslinking agents. The mixture was stirred and reacted at pH 5.5-6.5 and 25-30℃ for 4-6 h. After the reaction was completed, the mixture was purified by dialysis using a dialysis bag, with a molecular weight cutoff of 8000-14000 Da. The modified chitosan was obtained by freeze-drying.

[0017] Furthermore, the preparation method of calcium alginate-drug gel microspheres includes the following steps:

[0018] C1. Hydrophilic drugs: Dissolve directly in MES buffer at pH 6.0 at a concentration of 10 mg / mL, add 0.5% trehalose as a stabilizer to prepare a solution; Hydrophobic drugs: First disperse in anhydrous ethanol containing 1% Tween 80, sonicate at 200~300 W for 5~10 min, then slowly add dropwise to deionized water at a water-to-ethanol mass ratio of 6~9:1 to form a suspension.

[0019] C2. Weigh sodium alginate and add it to deionized water. Stir at 100-200 r / min for 10-15 min at room temperature 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℃ for 10-20 min to obtain a mixed solution.

[0020] C3. Under stirring conditions, the prepared mixed solution is added dropwise to the calcium chloride solution, the mass concentration of the calcium chloride solution is 2~5%, and the dropping rate is controlled at 1~3 mL / min to form calcium alginate-drug gel microspheres.

[0021] Furthermore, the microcapsules have a particle size of 5~20 μm and an encapsulation efficiency of ≥85%.

[0022] Furthermore, the preparation method of the microcapsule layer includes the following steps: dispersing the prepared microcapsules in deionized water to make 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.

[0023] 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%, then uniformly coating the hyaluronic acid solution onto the microcapsule layer, and naturally drying it at room temperature to form a hyaluronic acid film, i.e., the protective layer.

[0024] (iii) Beneficial technical effects

[0025] This invention relates to a medical dressing that uses a modified chitosan-sodium alginate composite wall material to prepare microcapsules. Through a dual cross-linking process and intelligent grafting technology, precise controlled release of antibiotics is achieved. The grafting of modified chitosan with poly(dimethylaminoethyl methacrylate) promotes the expansion of the wall material network, accelerating antibiotic release and rapidly inhibiting bacterial growth. In the neutral environment of normal tissue, the drug release rate is significantly reduced, minimizing systemic toxicity and improving drug utilization efficiency. The dual-layer cross-linking process of calcium alginate-drug gel microspheres and modified chitosan effectively reduces drug loss during preparation, ensuring that more antibiotics are encapsulated within the microcapsules, providing ample drug reserves for continuous antibacterial therapy.

[0026] This invention further reduces cytotoxicity by optimizing the preparation process and modifying materials, resulting in a significantly higher cell survival rate than traditional dressings. Simultaneously, the hyaluronic acid protective layer promotes cell adhesion and proliferation, accelerating wound healing; the nano-hydroxyapatite in the modified wall material can also induce tissue regeneration, creating a favorable microenvironment for wound repair.

[0027] This invention is applicable to various types of wounds, such as surgical incisions, burn wounds, and chronic ulcers. By adjusting the type of antibiotic in the microcapsule, the degree of cross-linking of the wall material, and the drug loading, it can meet the treatment needs of different wounds and has broad clinical application prospects. Detailed Implementation

[0028] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0029] Unless otherwise specified, all components of the microcapsule controlled-release medical dressing formulation of this invention are commercially available.

[0030] All parts used in this invention are by weight.

[0031] Example 1: A microcapsule controlled-release medical dressing includes a base fabric layer, a microcapsule layer disposed on one side of the base fabric layer, and a protective layer covering the microcapsule layer;

[0032] The microcapsule layer consists of multiple drug-loaded microcapsules, each microcapsule consisting of a wall material and a 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 nonwoven fabric with breathable pores, and the protective layer is a biodegradable hyaluronic acid film.

[0033] The medication used to treat the wound was an antibiotic.

[0034] The microcapsules have a particle size of 5~20 μm and an encapsulation efficiency of ≥85%.

[0035] The preparation method of the microcapsule layer includes the following steps: dispersing the prepared microcapsules in deionized water to make 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.

[0036] 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 uniformly coating the hyaluronic acid solution onto the microcapsule layer, and allowing it to dry naturally at room temperature to form a hyaluronic acid film, i.e., the protective layer.

[0037] The preparation method of microcapsules includes the following steps:

[0038] A1. Add 20 parts of modified chitosan to 800 parts of 1% acetic acid aqueous solution, stir at 150 r / min for 10 min in a 40℃ water bath to prepare a modified chitosan solution, and adjust the pH to 5.5.

[0039] A2. Disperse 60 parts of calcium alginate-drug gel microspheres in a modified chitosan solution and stir for 10 min at 20℃ and 100 r / min. Slowly add 80 parts of 0.1% genipin solution (50% ethanol aqueous solution) to 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 successively with 50% ethanol aqueous solution and deionized water, freeze-dry them, pre-freeze them at -50℃ for 2 h under a vacuum of <20 Pa to obtain the microcapsules.

[0040] The preparation method of modified chitosan includes the following steps:

[0041] B1. Weigh 60 parts of chitosan and dissolve it in a 1% acetic acid solution. Stir at 150 r / min for 15 min at 30℃ to prepare a 1% chitosan solution. Add 0.5% nano hydroxyapatite particles and ultrasonically disperse for 20 min at a frequency of 40 kHz.

[0042] B2. Dissolve 100 parts of dimethylaminoethyl methacrylate monomer and 0.5 parts of initiator azobisisobutyronitrile in 1000 parts of anhydrous ethanol. After purging with nitrogen for 10 min to remove oxygen, stir the reaction at 50°C for 2 h. After the reaction is completed, pour the product into ice-cold ether to precipitate it, and dry it under vacuum to obtain polydimethylaminoethyl methacrylate.

[0043] B3. Poly(dimethylaminoethyl methacrylate) was dissolved in 100 parts of N,N-dimethylformamide to prepare a poly(dimethylaminoethyl methacrylate) solution. Chitosan solution and poly(dimethylaminoethyl methacrylate) solution were mixed at a volume ratio of 10:1. Two parts of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and one part of N-hydroxysuccinimide were added as crosslinking agents. The mixture was stirred and reacted at pH 5.5 and 25℃ for 4 h. After the reaction was completed, the mixture was purified by dialysis using a dialysis bag. The molecular weight cutoff was 8000 Da. Modified chitosan was obtained by freeze drying.

[0044] The preparation method of calcium alginate-drug gel microspheres includes the following steps:

[0045] C1. Hydrophilic drugs: Dissolve directly in MES buffer at pH 6.0 at a concentration of 10 mg / mL, add 0.5% trehalose as a stabilizer to prepare a solution; Hydrophobic drugs: First disperse in anhydrous ethanol containing 1% Tween 80, sonicate at 200 W for 5 min, then slowly add dropwise to deionized water at a water-to-ethanol mass ratio of 6:1 to form a suspension.

[0046] C2. Weigh sodium alginate and add it to deionized water. Stir at 100 r / min for 10 min 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℃ for 10 min to obtain a mixed solution.

[0047] C3. Under stirring conditions, the prepared mixed solution is added dropwise to the calcium chloride solution, the mass concentration of the calcium chloride solution is 2%, and the dropping rate is controlled at 1 mL / min to form calcium alginate-drug gel microspheres.

[0048] 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;

[0049] The microcapsule layer consists of multiple drug-loaded microcapsules, each microcapsule consisting of a wall material and a 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 nonwoven fabric with breathable pores, and the protective layer is a biodegradable hyaluronic acid film.

[0050] The medication used to treat the wound was an antibiotic.

[0051] The microcapsules have a particle size of 5~20 μm and an encapsulation efficiency of ≥85%.

[0052] The preparation method of the microcapsule layer includes the following steps: dispersing the prepared microcapsules in deionized water to make 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.

[0053] 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 uniformly coating the hyaluronic acid solution onto the microcapsule layer, and allowing it to dry naturally at room temperature to form a hyaluronic acid film, i.e., the protective layer.

[0054] The preparation method of microcapsules includes the following steps:

[0055] A1. Add 30 parts of modified chitosan to 900 parts of 1% acetic acid aqueous solution, stir at 180 r / min for 10 min in a 50℃ water bath to prepare a modified chitosan solution, and adjust the pH to 5.5.

[0056] A2. Disperse 70 parts of calcium alginate-drug gel microspheres in a modified chitosan solution and stir for 15 min at 30℃ and 120 r / min. Slowly add 90 parts of 0.1% genipin solution (50% ethanol aqueous solution) to the system 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 successively with 50% ethanol aqueous solution and deionized water, freeze-dry them, pre-freeze them at -50℃ for 3 h under vacuum <20 Pa to obtain the microcapsules.

[0057] The preparation method of modified chitosan includes the following steps:

[0058] B1. Weigh 70 parts of chitosan and dissolve it in a 2% acetic acid solution. Stir at 200 r / min for 20 min at 40℃ to prepare a 2% chitosan solution. Add 1% nano hydroxyapatite particles and ultrasonically disperse for 20 min at a frequency of 50 kHz.

[0059] B2. Dissolve 120 parts of dimethylaminoethyl methacrylate monomer and 1 part of initiator azobisisobutyronitrile in 1200 parts of anhydrous ethanol. After purging with nitrogen for 20 min to remove oxygen, stir the reaction at 60℃ for 4 h. After the reaction is completed, pour the product into ice-cold ether to precipitate it, and dry it under vacuum to obtain polydimethylaminoethyl methacrylate.

[0060] B3. Poly(dimethylaminoethyl methacrylate) was dissolved in 120 parts of N,N-dimethylformamide to prepare a poly(dimethylaminoethyl methacrylate) solution. Chitosan solution and poly(dimethylaminoethyl methacrylate) solution were mixed at 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 crosslinking agents. The mixture was stirred and reacted at pH 6 and 28℃ for 5 h. After the reaction was completed, the mixture was purified by dialysis using a dialysis bag, with a molecular weight cutoff of 10000 Da. Modified chitosan was obtained by freeze-drying.

[0061] The preparation method of calcium alginate-drug gel microspheres includes the following steps:

[0062] C1. Hydrophilic drugs: Dissolve directly in MES buffer at pH 6.0 at a concentration of 10 mg / mL, add 0.5% trehalose as a stabilizer to prepare a solution; Hydrophobic drugs: First disperse in anhydrous ethanol containing 1% Tween 80, sonicate at 250 W for 5 min, then slowly add dropwise to deionized water at a water-to-ethanol mass ratio of 7:1 to form a suspension.

[0063] C2. Weigh sodium alginate and add it to deionized water. Stir at 150 r / min for 10 min at room temperature 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℃ for 15 min to obtain a mixed solution.

[0064] C3. Under stirring conditions, the prepared mixed solution is added dropwise to the calcium chloride solution, the mass concentration of the calcium chloride solution is 3%, and the dropping rate is controlled at 2 mL / min to form calcium alginate-drug gel microspheres.

[0065] 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;

[0066] The microcapsule layer consists of multiple drug-loaded microcapsules, each microcapsule consisting of a wall material and a 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 nonwoven fabric with breathable pores, and the protective layer is a biodegradable hyaluronic acid film.

[0067] The medication used to treat the wound was an antibiotic.

[0068] The microcapsules have a particle size of 5~20 μm and an encapsulation efficiency of ≥85%.

[0069] The preparation method of the microcapsule layer includes the following steps: dispersing the prepared microcapsules in deionized water to make 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.

[0070] 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 uniformly coating the hyaluronic acid solution onto the microcapsule layer, and allowing it to dry naturally at room temperature to form a hyaluronic acid film, i.e., the protective layer.

[0071] The preparation method of microcapsules includes the following steps:

[0072] A1. Add 40 parts of modified chitosan to 1000 parts of 1% acetic acid aqueous solution, stir at 200 r / min for 15 min in a 60℃ water bath to prepare a modified chitosan solution, and adjust the pH to 6.

[0073] A2. Disperse 80 parts of calcium alginate-drug gel microspheres in a modified chitosan solution and stir for 20 min at 40℃ and 150 r / min. Slowly add 100 parts of 0.1% genipin solution (50% ethanol aqueous solution) to 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 successively with 50% ethanol aqueous solution and deionized water, freeze-dry them, pre-freeze them at -50℃ for 4 h under a vacuum of <20 Pa to obtain the microcapsules.

[0074] The preparation method of modified chitosan includes the following steps:

[0075] B1. Weigh 80 parts of chitosan and dissolve it in a 3% acetic acid solution. Stir at 250 r / min for 30 min at 50℃ to prepare a 3% chitosan solution. Add 1.5% nano hydroxyapatite particles and ultrasonically disperse for 30 min at a frequency of 60 kHz.

[0076] B2. Dissolve 150 parts of dimethylaminoethyl methacrylate monomer and 1.5 parts of initiator azobisisobutyronitrile in 1500 parts of anhydrous ethanol. After purging with nitrogen for 30 min to remove oxygen, stir the reaction at 70℃ for 6 h. After the reaction is completed, pour the product into ice-cold ether to precipitate it, and dry it under vacuum to obtain polydimethylaminoethyl methacrylate.

[0077] B3. Poly(dimethylaminoethyl methacrylate) was dissolved in 150 parts of N,N-dimethylformamide to prepare a poly(dimethylaminoethyl methacrylate) solution. Chitosan solution and poly(dimethylaminoethyl methacrylate) solution were mixed at 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 crosslinking agents. The mixture was stirred and reacted at pH 6.5 and 30℃ for 4-6 h. After the reaction was completed, the mixture was purified by dialysis using a dialysis bag. The molecular weight cutoff was 14000 Da. The modified chitosan was obtained by freeze-drying.

[0078] The preparation method of calcium alginate-drug gel microspheres includes the following steps:

[0079] C1. Hydrophilic drugs: Dissolve directly in MES buffer at pH 6.0 at a concentration of 10 mg / mL, add 0.5% trehalose as a stabilizer to prepare a solution; Hydrophobic drugs: First disperse in anhydrous ethanol containing 1% Tween 80, sonicate at 300 W for 10 min, then slowly add dropwise to deionized water at a water-to-ethanol mass ratio of 9:1 to form a suspension.

[0080] C2. Weigh sodium alginate and add it to deionized water. Stir at 200 r / min for 15 min at room temperature 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℃ for 20 min to obtain a mixed solution.

[0081] C3. Under stirring conditions, the prepared mixed solution is added dropwise to the calcium chloride solution, the mass concentration of the calcium chloride solution is 5%, and the dropping rate is controlled at 3 mL / min to form calcium alginate-drug gel microspheres.

[0082] Comparative Example 1: Unmodified chitosan, with the remaining processes the same as in Example 1.

[0083] Comparative Example 2: The microcapsule wall material is sodium alginate alone, and the rest of the process is the same as in Example 1.

[0084] Comparative Example 3: The microcapsule wall material is a common chitosan-sodium alginate composite wall material, without the addition of nano-hydroxyapatite, and the rest of the process is the same as in Example 1.

[0085] Experimental example:

[0086] 1. Drug encapsulation efficiency test

[0087] High-performance liquid chromatography (HPLC) was used. A specific mass of microcapsule sample was accurately weighed, and an appropriate amount of demulsifier (such as ethanol) was added to dissolve the microcapsule wall material and release the drug. After centrifugation (8000 r / min, 15 min), the supernatant was collected for HPLC analysis.

[0088] 2. Controlled-release performance test

[0089] Microcapsules were placed in simulated body fluid (PBS buffer at pH 7.4) and release experiments were conducted under isothermal shaking conditions at 37°C (shaking speed 100 r / min). 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 simultaneously. The drug concentration in the samples was determined using high-performance liquid chromatography (HPLC), and cumulative drug release curves were plotted to analyze the release rate and release pattern.

[0090] 3. Biocompatibility testing

[0091] Cytotoxicity was detected using the MTT assay. L929 mouse fibroblasts were injected with 1×10⁻⁶ cells. 4 The samples were seeded at a density of 1 sample per well in 96-well plates. After 24 h of incubation, different sample extraction solutions were added (the dressing samples were soaked in DMEM medium at a ratio of 1 g / mL, shaken at 37°C for 24 h, and the supernatant was used as the extraction solution). A blank control group (containing only DMEM medium) and a positive control group (containing DMEM medium with 0.1% Triton X-100) were also set up. After another 24 h of incubation, 20 μL of LMT solution (5 mg / mL) was added to each well, and the plates were incubated at 37°C for 4 h. The supernatant was discarded, and 150 μL of dimethyl sulfoxide (DMSO) was added. The plates were shaken for 10 min to fully dissolve the formazan, and the absorbance (OD value) was measured at 570 nm using a microplate reader.

[0092] Table 1 Results of Drug Encapsulation Efficiency Test

[0093]

[0094] Table 2 Results of controlled-release performance tests

[0095]

[0096] Table 3 Biocompatibility test results

[0097]

[0098] As shown in the table, the embodiments outperform 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 material and optimizing the preparation process, providing a better solution for the development of microcapsule controlled-release medical dressings.

[0099] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A microcapsule controlled-release medical dressing, characterized in that, It includes 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 consists of multiple drug-loaded microcapsules, each microcapsule consisting of a wall material and a 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 nonwoven fabric with breathable pores, and the protective layer is a biodegradable hyaluronic acid film. The preparation method of modified chitosan includes the following steps: B1. Weigh 60-80 parts of chitosan and dissolve it in a 1-3% acetic acid solution. Stir at 150-250 r / min for 15-30 min at 30-50℃ to prepare a 1-3% chitosan solution. Add 0.5-1.5% nano-hydroxyapatite particles and ultrasonically disperse for 20-30 min at a frequency of 40-60 kHz. B2. Dissolve 100-150 parts of dimethylaminoethyl methacrylate monomer and 0.5-1.5 parts of initiator azobisisobutyronitrile in 1000-1500 parts of anhydrous ethanol. After purging with nitrogen for 10-30 min, stir the reaction at 50-70℃ for 2-6 h. After the reaction is complete, pour the product into ice-cold ether to precipitate it, and dry it under vacuum to obtain polydimethylaminoethyl methacrylate. B3. Poly(dimethylaminoethyl methacrylate) solution was prepared by dissolving 100-150 parts of N,N-dimethylformamide. Chitosan solution and poly(dimethylaminoethyl methacrylate) solution were mixed at 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 crosslinking agents. The mixture was stirred and reacted at pH 5.5-6.5 and 25-30℃ for 4-6 h. After the reaction was completed, the mixture was purified by dialysis using a dialysis bag, with a molecular weight cutoff of 8000-14000 Da. The modified chitosan was obtained by freeze-drying.

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

3. The microcapsule controlled-release medical dressing according to claim 1, characterized in that, The preparation method of microcapsules includes 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 r / min for 10-15 min under water bath conditions of 40-60℃ to prepare 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 for 10-20 min at 20-40℃ and 100-150 r / min, slowly add 80-100 parts of 0.1% genipin solution (50% ethanol aqueous solution) to the system, 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 sequentially with 50% ethanol aqueous solution and deionized water, freeze-dry, pre-freeze at -50℃ for 2-4 h under vacuum <20 Pa to obtain the microcapsules.

4. The microcapsule controlled-release medical dressing according to claim 3, characterized in that, The preparation method of calcium alginate-drug gel microspheres includes the following steps: C1. Hydrophilic drugs: Dissolve directly in MES buffer at pH 6.0 at a concentration of 10 mg / mL, add 0.5% trehalose as a stabilizer to prepare a solution; Hydrophobic drugs: First disperse in anhydrous ethanol containing 1% Tween 80, sonicate at 200~300 W for 5~10 min, then slowly add dropwise to deionized water at a water-to-ethanol mass ratio of 6~9:1 to form a suspension. C2. Weigh sodium alginate and add it to deionized water. Stir at 100-200 r / min for 10-15 min at room temperature 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℃ for 10-20 min to obtain a mixed solution. C3. Under stirring conditions, the prepared mixed solution is added dropwise to the calcium chloride solution, the mass concentration of the calcium chloride solution is 2~5%, and the dropping rate is controlled at 1~3 mL / min to form calcium alginate-drug gel microspheres.

5. A microcapsule controlled-release medical dressing according to claim 3, characterized in that, The microcapsules have a particle size of 5~20μm and an encapsulation efficiency of ≥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 make 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 uniformly coating the hyaluronic acid solution onto the microcapsule layer, and allowing it to dry naturally at room temperature to form a hyaluronic acid film, i.e., the protective layer.

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