CN104189942A - Antibacterial wound dressing and preparation method thereof - Google Patents
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Abstract
本发明提供了一种抗菌复合型创伤敷料及其制备方法。所述的抗菌复合型创伤敷料,其特征在于,包括从上到下依次设置的壳聚糖基载药复合抗菌型超细纤维膜、海藻酸钙纤维非织布和支撑保护层。本发明采用静电纺丝方法制得的载药超细纤维膜,能有效增大药剂的表面积,利用超细纤维高的孔隙率,均匀的孔径,药物可以缓慢持续的释放,使药物能够充分地被人体吸收,无需频繁给药,即可保持药物的作用效果,降低了药物的毒副作用。The invention provides an antibacterial composite wound dressing and a preparation method thereof. The antibacterial composite wound dressing is characterized in that it comprises a chitosan-based drug-loaded composite antibacterial superfine fiber membrane, calcium alginate fiber nonwoven fabric and a supporting protective layer arranged sequentially from top to bottom. The drug-loaded ultra-fine fiber membrane prepared by the electrospinning method in the present invention can effectively increase the surface area of the drug, and utilize the high porosity and uniform pore diameter of the ultra-fine fiber to release the drug slowly and continuously, so that the drug can be fully Absorbed by the human body, the effect of the drug can be maintained without frequent administration, and the toxic and side effects of the drug are reduced.
Description
技术领域technical field
本发明属于复合抗菌型创伤敷料的制备技术领域,具体涉及一种具有抗菌、止血、愈创作用的新型医用敷料及其制备方法。The invention belongs to the technical field of preparation of composite antibacterial wound dressings, and in particular relates to a novel medical dressing with antibacterial, hemostatic and healing functions and a preparation method thereof.
背景技术Background technique
目前针对因创伤、烫伤、烧伤、褥疮、糖尿病溃疡、静脉曲张溃疡以及手术切口等导致的皮肤损伤,主要是采用传统敷料进行护理。但存在无抗菌性、透气性差、易粘连等缺陷,易导致皮肤反复破坏、受损,使愈合速度减慢,引起二次细菌感染等不良后果。其中,细菌感染是影响创面愈合的主要因素之一,创面渗出液中含有大量的炎症因子、蛋白酶和自由基都会影响创面的愈合速度。新型复合抗菌型敷料的研发对治疗皮肤损伤具有重要的意义,是新型创伤敷料发展的必然趋势。At present, traditional dressings are mainly used for nursing care of skin injuries caused by trauma, scalds, burns, bedsores, diabetic ulcers, varicose ulcers, and surgical incisions. However, there are defects such as no antibacterial properties, poor air permeability, and easy adhesion, which can easily lead to repeated damage and damage to the skin, slow down the healing speed, and cause adverse consequences such as secondary bacterial infections. Among them, bacterial infection is one of the main factors affecting wound healing. Wound exudate contains a large number of inflammatory factors, proteases and free radicals, which will affect the speed of wound healing. The development of new composite antibacterial dressings is of great significance to the treatment of skin injuries, and is an inevitable trend in the development of new wound dressings.
壳聚糖(Chitosan)是一种天然高分子材料,是自然界天然存在的聚阳离子型电解质,本身具有抗菌、止血和愈创的作用,低毒、生物可降解,对皮肤和粘膜无刺激性,而且具有粘膜粘附性。由于壳聚糖具有良好的生物特性,对创面修复具有积极的促进作用,是广泛承认的良好的创面修复材料。壳聚糖大分子上具有很多活性基团,可实现对药物负载和控制释放,是一种良好的药物载体材料,虽然,目前以壳聚糖作为药物载体的研究较多,但其主要形式多为浇铸膜、海绵及微球,或以直径10μm左右的单纤维构成的非织布或织物。静电纺丝制得的超细纤维膜具有纤维直径细、比表面积大、孔隙率高等特点,该结构特征用作载体材料显示出独特的性能。Chitosan (Chitosan) is a natural polymer material and a polycation electrolyte naturally occurring in nature. It has antibacterial, hemostatic and healing effects, low toxicity, biodegradable, and non-irritating to skin and mucous membranes. And it is mucoadhesive. Because chitosan has good biological characteristics, it has a positive effect on promoting wound repair, and it is widely recognized as a good wound repair material. There are many active groups on the chitosan macromolecule, which can realize drug loading and controlled release. It is a good drug carrier material. Although there are many studies on chitosan as a drug carrier, its main form It is cast film, sponge and microsphere, or non-woven fabric or fabric composed of single fiber with a diameter of about 10 μm. The ultrafine fiber membrane prepared by electrospinning has the characteristics of fine fiber diameter, large specific surface area, and high porosity. This structural feature shows unique properties when used as a carrier material.
海藻酸盐是由褐色海藻中提取的藻蛋白酸加工而成,成本低廉,加工过程使用的材料没有任何毒性。以海藻酸盐为原料研发的藻酸盐纤维具有无毒性、高吸水成凝胶性、高透氧性、良好的生物相容性、良好的生物降解吸收性、止血性能、有效促进伤口愈合、高离子吸附性等优越特性,已被广泛应用于生物医学的研究。此外,海藻酸钙具有良好的吸液性能,能够吸收相当于自身重量20倍的渗出物,为普通纱布的5-7倍。当与创面渗出液接触时,通过离子交换产生可溶性的海藻酸钠,同时释放钙离子到伤口中,诱导血小板活化,加速创面的愈合;海藻酸钙还可以吸附细菌,阻止细菌进入创面,活化巨噬细胞来抵御病原微生物的入侵。Alginate is processed from alginic acid extracted from brown seaweed, and the cost is low, and the materials used in the processing process are not toxic. The alginate fiber developed with alginate as raw material is non-toxic, highly water-absorbing and gelling, high oxygen permeability, good biocompatibility, good biodegradable absorption, hemostatic performance, and effectively promotes wound healing. High ion adsorption and other superior properties have been widely used in biomedical research. In addition, calcium alginate has good liquid absorption performance, and can absorb exudates equivalent to 20 times its own weight, which is 5-7 times that of ordinary gauze. When in contact with wound exudate, soluble sodium alginate is produced through ion exchange, and at the same time calcium ions are released into the wound to induce platelet activation and accelerate wound healing; calcium alginate can also adsorb bacteria, prevent bacteria from entering the wound, and activate Macrophages defend against the invasion of pathogenic microorganisms.
在已有专利中,公开号CN 102600497A公开了一种银离子抗菌医用敷料,将附着银离子的抗菌剂与粘胶纤维混和后织布,制备出具有较强抗感染能力的产品。但是该种方法制备的敷料仅具备抗菌、抑菌的功能,对于改善创口、加快伤口愈合及透气性能并没有涉及。公开号CN 102335451 A公开制备出由水溶性甲壳素和甲基胍组成的敷料,具有促愈和抑菌作用,但该种产品的吸液性较差。公开号CN 102264323 A公开了一种创伤敷料,制备出的敷料具有支撑层(聚合物膜)和吸收层,吸收垫包括至少两个彼此不同的吸收层(粘胶纤维和热塑性纤维),通过第三层(含银抗菌剂)间隔,至少一种抗菌剂在吸收垫内发挥其作用,解决了抗菌剂超负荷的现象。专利号为US 8293964B2公开了一种以含银织物的抗菌层作为第一层,其他两层由吸收组织渗出液的吸收层(无孔的弹性材料组成)和透气不透水的支撑层组成,能够预防伤口感染,促进伤口愈合的医用敷料。专利号为US 7030288 B2公开了一种由吸收层(粘胶纤维等)、载药层(抗菌剂)、粘附层(压敏粘着剂)以及支撑层(聚酯等)组成,可以负载抗生素类药物达到抗菌的效果,吸收层能够有效的吸收组织渗出液,加快伤口的愈合。公开号CN103611182 A公开了一种以同轴静电纺的方法制备出了载有机抗菌药的创伤敷料,具有良好的抗菌性、吸水性和透气性,利用纳米纤维高的孔隙率和大的比表面积,使得负载的抗菌药能够持续稳定的释放,达到持久的抗菌效果。Among the existing patents, Publication No. CN 102600497A discloses a silver ion antibacterial medical dressing, which mixes an antibacterial agent with silver ions and viscose fiber before weaving to prepare a product with strong anti-infection ability. However, the dressing prepared by this method only has antibacterial and antibacterial functions, and does not involve in improving wounds, accelerating wound healing and breathability. Publication number CN 102335451 A discloses the preparation of a dressing composed of water-soluble chitin and methylguanidine, which has healing-promoting and antibacterial effects, but the liquid absorption of this product is poor. Publication number CN 102264323 A discloses a wound dressing. The prepared dressing has a support layer (polymer film) and an absorbent layer. The absorbent pad includes at least two different absorbent layers (viscose fiber and thermoplastic fiber). Three layers (containing silver antibacterial agent) are separated, and at least one antibacterial agent plays its role in the absorbent pad, which solves the phenomenon of antibacterial agent overload. Patent No. US 8293964B2 discloses an antibacterial layer of silver-containing fabric as the first layer, and the other two layers are composed of an absorbent layer (non-porous elastic material) that absorbs tissue exudates and an air-permeable and impermeable support layer. A medical dressing that can prevent wound infection and promote wound healing. The patent No. US 7030288 B2 discloses a method consisting of an absorbent layer (viscose fiber, etc.), a drug-loaded layer (antibacterial agent), an adhesive layer (pressure-sensitive adhesive) and a support layer (polyester, etc.), which can be loaded with antibiotics. The antibacterial effect of similar drugs is achieved, and the absorbent layer can effectively absorb tissue exudate and accelerate wound healing. Publication number CN103611182 A discloses a wound dressing loaded with organic antibacterial drugs prepared by coaxial electrospinning, which has good antibacterial properties, water absorption and air permeability, and utilizes the high porosity and large specific surface area of nanofibers , so that the loaded antibacterial drugs can be released continuously and stably, achieving a lasting antibacterial effect.
目前负载抗菌剂的抗菌敷料的研究中,多以负载银抗菌敷料的研究和应用为主,对于载有有机抗菌剂药物的报道很少,但是,有关纳米银对人体的生物负效应,尤其是长期频繁使用或大量使用时的慢性毒性反应尚不十分清楚。又由于负载有机抗菌药物复合敷料具有起效迅速、抗菌作用明显,在制备过程不会破坏基材及药物活性,在治疗期限不会产生明显耐药性等优点,同时,以海藻酸盐纤维做吸收层能够有效的吸收组织渗出液,保持伤口的湿润环境,并具有一定的止血功能。At present, in the research on antibacterial dressings loaded with antibacterial agents, most of them are based on the research and application of silver-loaded antibacterial dressings, and there are few reports on drugs loaded with organic antibacterial agents. However, the biological negative effects of nano-silver on the human body, especially The chronic toxicity of long-term frequent use or large-scale use is not very clear. And because the composite dressing loaded with organic antibacterial drugs has the advantages of rapid onset and obvious antibacterial effect, it will not destroy the substrate and drug activity during the preparation process, and will not produce obvious drug resistance during the treatment period. At the same time, it is made of alginate fiber. The absorbent layer can effectively absorb tissue exudate, maintain a moist environment of the wound, and have a certain hemostatic function.
发明内容Contents of the invention
本发明的目的是提出一种以壳聚糖为载体负载有机抗菌药复合超细纤维膜作为抗菌层、以海藻酸盐非织造布作为吸收层、以疏水透气的聚酯等材料作为支撑层的抗菌型创伤敷料及其制备方法。基于静电纺丝成膜技术,利用壳聚糖作为载药体系,降低了药物在载体中的扩散速度,延长了释放时间,使得药物在人体伤口处逐级释放,无需频繁给药,也可以在较长时间内维持伤口处有效的药物浓度。以海藻酸酸盐材料作为吸收体系,能够有效的吸收组织渗出液,成凝胶状态,保持伤口的湿润环境,促进伤口的愈合。同时发挥壳聚糖与海藻酸盐的止血性能。支撑层既保证了敷料的柔软性和透气性,又能较好的阻隔外界的水分。这种多层复合结构,集合了各层材料的优点,能够很好的满足患者伤口修复,及医护人员的护理治疗需求。The purpose of the present invention is to propose a kind of antimicrobial compound microfiber film that uses chitosan as the carrier to load organic antibacterial drugs as the antibacterial layer, uses alginate non-woven fabric as the absorption layer, and uses materials such as hydrophobic and breathable polyester as the support layer. Antibacterial wound dressing and preparation method thereof. Based on electrospinning film-forming technology, chitosan is used as the drug-loading system, which reduces the diffusion rate of the drug in the carrier and prolongs the release time, allowing the drug to be released step by step at the wound of the human body without frequent administration. Maintain the effective drug concentration at the wound for a long time. The alginate material is used as the absorption system, which can effectively absorb tissue exudate, form a gel state, maintain a moist environment of the wound, and promote wound healing. At the same time, it exerts the hemostatic properties of chitosan and alginate. The support layer not only ensures the softness and air permeability of the dressing, but also can better block the external moisture. This multi-layer composite structure combines the advantages of each layer of materials, and can well meet the needs of patients for wound repair and medical care for medical staff.
为了达到上述目的,本发明提供了一种抗菌复合型创伤敷料,其特征在于,包括从上到下依次设置的壳聚糖基载药复合抗菌型超细纤维膜(1)、海藻酸钙纤维非织布(2)和支撑保护层(3)。In order to achieve the above object, the present invention provides an antibacterial composite wound dressing, which is characterized in that it comprises a chitosan-based drug-loaded composite antibacterial microfiber membrane (1), calcium alginate fiber and Non-woven fabric (2) and supporting protective layer (3).
优选地,所述的支撑保护层(3)为聚丙烯酸酯压敏胶、聚氨酯膜、聚乙烯膜、聚丙烯纤维的非织布、乙丙复合纤维(ES纤维)的非织布或聚丙烯纤维和乙丙复合纤维的混和物的非织布。Preferably, the support protection layer (3) is polyacrylate pressure-sensitive adhesive, polyurethane film, polyethylene film, non-woven fabric of polypropylene fiber, non-woven fabric of ethylene-propylene composite fiber (ES fiber) or polypropylene A nonwoven fabric made of a blend of fibers and ethylene-propylene composite fibers.
本发明还提供了上述的抗菌复合型创伤敷料的制备方法,其特征在于,具体步骤包括:The present invention also provides the preparation method of above-mentioned antibacterial composite wound dressing, it is characterized in that, concrete steps comprise:
第一步:在质量分数为2-95%的醋酸水溶液中加入抗菌药物粉末,用磁力搅拌器搅拌使其充分溶解,称取壳聚糖和聚氧化乙烯粉末加入到上述溶液中,搅拌得到纺丝溶液;在纺丝电压为8-30Kv、纺丝液给进速率为0.08-1.2mL/h、接收距离为10-35cm、环境温度为15-50℃以及相对湿度为20-60%的条件下进行静电纺丝,将得到的纳米纤维膜置于盛有20-30%戊二醛水溶液的干燥器中,进行交联12-36h后置于真空干燥箱中干燥12-36h,以除去残留溶剂和交联剂戊二醛,得到壳聚糖基载药复合抗菌型超细纤维膜(1),其纤维直径为150-400nm;The first step: add antimicrobial drug powder into the aqueous solution of acetic acid with a mass fraction of 2-95%, stir it with a magnetic stirrer to make it fully dissolve, weigh chitosan and polyethylene oxide powder and add it to the above solution, and stir to obtain spinning Silk solution; under the conditions of spinning voltage of 8-30Kv, spinning solution feed rate of 0.08-1.2mL/h, receiving distance of 10-35cm, ambient temperature of 15-50°C and relative humidity of 20-60% Electrospinning is carried out under the environment, and the obtained nanofiber membrane is placed in a desiccator filled with 20-30% glutaraldehyde aqueous solution, cross-linked for 12-36 hours, and then dried in a vacuum oven for 12-36 hours to remove residual Solvent and cross-linking agent glutaraldehyde to obtain chitosan-based drug-loaded composite antibacterial microfiber membrane (1), the fiber diameter of which is 150-400nm;
第二步:采用海藻酸钙纤维,依次经过开松、梳理、铺网和水刺,制得海藻酸钙纤维非织布(2),作为组织渗透液吸收层;Step 2: Calcium alginate fiber is used, followed by opening, carding, web laying and spunlace in sequence to prepare calcium alginate fiber non-woven fabric (2), which is used as the absorption layer of tissue infiltration fluid;
第三步:将壳聚糖基载药复合抗菌型超细纤维膜(1)与海藻酸钙纤维非织布(2)使用生物粘合剂粘合在一起,再与支撑保护层(3)复合,经过分切成为一定规格的抗菌复合型创伤敷料。The third step: the chitosan-based drug-loaded composite antibacterial microfiber membrane (1) and the calcium alginate fiber non-woven fabric (2) are bonded together with a bioadhesive, and then bonded with the supporting protective layer (3) Composite, cut into a certain specification of antibacterial composite wound dressing.
优选地,所述第一步中的纺丝溶液中聚氧化乙烯的浓度为0.3-0.6wt%,壳聚糖与聚氧化乙烯的重量比为10-93∶10,抗菌药物与聚氧化乙烯的重量比为5-15∶10。Preferably, the concentration of polyethylene oxide in the spinning solution in the first step is 0.3-0.6wt%, the weight ratio of chitosan to polyethylene oxide is 10-93:10, the ratio of antibacterial drugs to polyethylene oxide The weight ratio is 5-15:10.
优选地,所述第一步中的壳聚糖为白色粉末,脱乙酰度>95%,级别为医用级,聚氧化乙烯为白色粉末,分子量为400-1000KDa。Preferably, the chitosan in the first step is a white powder with a degree of deacetylation>95%, and its grade is medical grade, and the polyoxyethylene is a white powder with a molecular weight of 400-1000KDa.
优选地,所述第一步中的抗菌药物为盐酸莫西沙星、盐酸环丙沙星、美福仙(头孢西丁钠)、盐酸左氧沙星、阿莫西林或盐酸四环素。Preferably, the antibacterial drug in the first step is moxifloxacin hydrochloride, ciprofloxacin hydrochloride, mefoxin (cefoxitin sodium), levofloxacin hydrochloride, amoxicillin or tetracycline hydrochloride.
优选地,所述第二步中的梳理和铺网工艺参数为:梳理机喂入速度0.2-0.9m/min,锡林速度500-900m/min,输出纤网速度为40-70m/min,铺网速度为40-60m/min,输出纤网的不匀率为1.5-4%。Preferably, the carding and laying process parameters in the second step are: carding machine feeding speed 0.2-0.9m/min, cylinder speed 500-900m/min, output fiber web speed 40-70m/min, The web laying speed is 40-60m/min, and the unevenness of the output web is 1.5-4%.
优选地,所述第三步中的分切速度为100-400m/min。Preferably, the cutting speed in the third step is 100-400m/min.
优选地,所得的抗菌复合型创伤敷料的吸液率为500-2000%,保液率为600-1000%,抑菌圈直径为10-35mm。Preferably, the liquid absorption rate of the obtained antibacterial composite wound dressing is 500-2000%, the liquid retention rate is 600-1000%, and the diameter of the antibacterial zone is 10-35mm.
优选地,所述的壳聚糖基载药复合抗菌型超细纤维膜(1)的载药率90-96%。Preferably, the drug-loading rate of the chitosan-based drug-loaded composite antibacterial microfiber membrane (1) is 90-96%.
与现有技术相比,本发明的有益效果是:Compared with prior art, the beneficial effect of the present invention is:
1.本发明采用静电纺丝方法制得的载药超细纤维膜,能有效增大药剂的表面积,利用超细纤维高的孔隙率,均匀的孔径,药物可以缓慢持续的释放,使药物能够充分地被人体吸收,无需频繁给药,即可保持药物的作用效果,降低了药物的毒副作用。1. The drug-loaded ultra-fine fiber membrane prepared by the electrospinning method of the present invention can effectively increase the surface area of the drug, and utilize the high porosity and uniform pore size of the ultra-fine fiber to release the drug slowly and continuously, so that the drug can Fully absorbed by the human body, without frequent administration, the effect of the drug can be maintained, and the toxic and side effects of the drug can be reduced.
2.本发明的载药纤维膜材以壳聚糖为载体,壳聚糖本身具有广谱抗菌、止血、愈创,以及良好的生物相容性和生物可降解性,用作敷料时可与抗菌药物协同抗菌,形成复合型抗菌效果。还可根据需要设计不同载药量的敷料用于不同程度的创面治疗,有效地促进伤口愈合。2. The drug-loaded fiber membrane material of the present invention takes chitosan as a carrier, and chitosan itself has broad-spectrum antibacterial, hemostasis, wound healing, and good biocompatibility and biodegradability, and can be used as a dressing with Antibacterial drugs work together to form a compound antibacterial effect. Dressings with different drug loadings can also be designed for different degrees of wound treatment according to needs, effectively promoting wound healing.
3.本发明的超细纤维膜柔软易于与皮肤贴合,具有良好的柔韧性,使用创面敷料时,可根据伤口的大小进行裁剪,减轻敷料对创面组织的刺激作用。同时,也可以防止创面粘连,避免二次创伤的产生。3. The microfiber membrane of the present invention is soft and easy to fit with the skin, and has good flexibility. When using a wound dressing, it can be cut according to the size of the wound to reduce the irritation of the dressing on the wound tissue. At the same time, it can also prevent wound adhesion and avoid secondary trauma.
4.本发明的海藻酸钙纤维具有良好的吸液性能,能够吸收相当于自身重量20倍的渗出物,为普通纱布的5-7倍,可以有效防止伤口积液感染。当与创面渗液接触时,通过离子交换生产可溶性的海藻酸钠,同时释放钙离子到伤口中,诱导血小板活化,加速创面愈合。4. The calcium alginate fiber of the present invention has good liquid absorption performance, can absorb exudate equivalent to 20 times its own weight, which is 5-7 times that of ordinary gauze, and can effectively prevent wound effusion infection. When in contact with wound exudate, soluble sodium alginate is produced through ion exchange, and calcium ions are released into the wound at the same time, which induces platelet activation and accelerates wound healing.
5.本发明的支撑保护层采用具有良好的耐水性、抗渗性材料,能够很好的阻止外界细菌及微生物和水分的入侵,防水等级可达4-5级之间。5. The supporting protection layer of the present invention adopts materials with good water resistance and impermeability, which can well prevent the invasion of external bacteria, microorganisms and moisture, and the waterproof level can reach between 4-5.
6.本发明所选材料,制备工艺简单,来源广泛,价廉易得,环保可生物降解,通过医用粘合剂即可组合成抗菌型医用敷料,适合批量生产,同时能够减少医疗废物的产生。6. The materials selected in the present invention have simple preparation process, wide sources, cheap and easy to obtain, and are environmentally friendly and biodegradable. They can be combined into antibacterial medical dressings through medical adhesives, which are suitable for mass production and can reduce the generation of medical waste at the same time .
7.本发明方法制备的抗菌性创伤敷料,能用于临床上的手术切口、创伤、烧伤、烫伤、褥疮或溃疡等皮肤创伤的修复。7. The antibacterial wound dressing prepared by the inventive method can be used for the repair of skin wounds such as clinical surgical incisions, wounds, burns, scalds, bedsores or ulcers.
附图说明Description of drawings
图1为本发明的抗菌型复合功能性创伤敷料的结构示意图,其中1-抗菌层,2-吸水层,3-支撑层。Fig. 1 is a schematic structural view of the antibacterial composite functional wound dressing of the present invention, wherein 1-antibacterial layer, 2-absorbent layer, 3-support layer.
图2为实施例1中得到的负载盐酸环丙沙星超细纤维的扫描电镜图片;Fig. 2 is the scanning electron microscope picture of the loaded ciprofloxacin hydrochloride superfine fiber that obtains in embodiment 1;
图3为实施例3中得到的负载盐酸莫西沙星超细纤维的扫描电镜图片;Fig. 3 is the scanning electron microscope picture of the loaded moxifloxacin hydrochloride superfine fiber that obtains in embodiment 3;
图4为实施例1中得到的负载盐酸环丙沙星复合型抗菌敷料的外形图。Fig. 4 is the outline drawing of the loaded ciprofloxacin hydrochloride composite antibacterial dressing obtained in embodiment 1.
图5为实施例1、2、3中得到的负载盐酸环丙沙星超细纤维的抗菌效果图;Fig. 5 is the antibacterial effect figure of the loaded ciprofloxacin hydrochloride microfiber obtained in embodiment 1,2,3;
图6为实施例4中得到的负载盐酸莫西沙星超细纤维的抗菌效果图;Fig. 6 is the antibacterial effect figure of the loaded moxifloxacin hydrochloride microfiber obtained in embodiment 4;
具体实施方式Detailed ways
为使本发明更明显易懂,兹以优选实施例,作详细说明如下。以下实施例中所用的壳聚糖(CS)为白色粉末,脱乙酰度>95%,级别为医用级。所述的聚氧化乙烯(PEO)为白色粉末,分子量为400-1000KDa。In order to make the present invention more comprehensible, preferred embodiments are described in detail as follows. Chitosan (CS) used in the following examples is a white powder with a degree of deacetylation>95%, and its grade is medical grade. The polyethylene oxide (PEO) is a white powder with a molecular weight of 400-1000KDa.
实施例1Example 1
如图1所示,为本发明的抗菌复合型创伤敷料的结构示意图,所述的抗菌复合型创伤敷料,包括从上到下依次设置的壳聚糖基载药复合抗菌型超细纤维膜1、海藻酸钙纤维非织布2和支撑保护层3。所述的支撑保护层3为聚丙烯酸酯压敏胶。As shown in Figure 1, it is a schematic structural view of the antibacterial composite wound dressing of the present invention, and the antibacterial composite wound dressing includes a chitosan-based drug-loaded composite antibacterial microfiber membrane 1 sequentially arranged from top to bottom , calcium alginate fiber non-woven fabric 2 and support protection layer 3. The supporting protective layer 3 is polyacrylate pressure-sensitive adhesive.
所述的抗菌复合型创伤敷料的制备方法的具体步骤为:The concrete steps of the preparation method of described antibacterial composite wound dressing are:
在质量分数为90%的醋酸水溶液中加入抗菌药物盐酸环丙沙星粉末,用磁力搅拌器搅拌使其充分溶解,称取壳聚糖和聚氧化乙烯粉末加入到上述溶液中,搅拌得到均一、稳定的纺丝溶液,所述的纺丝溶液中聚氧化乙烯的浓度为0.5wt%,壳聚糖与聚氧化乙烯的重量比为90∶10,抗菌药物与聚氧化乙烯的重量比为5∶10,在纺丝电压为16kv、纺丝液给进速率为0.5mL/h、接收距离为20cm、环境温度为25℃以及相对湿度为35%的条件下进行静电纺丝8h,将制得的纳米纤维膜置于盛有25%戊二醛水溶液的干燥器中,进行交联24h后置于真空干燥箱中干燥24h,以除去残留溶剂和交联剂戊二醛,最后在干燥器中避光保存。如图2所示,所得的壳聚糖基载药复合抗菌超细纤维膜的纤维直径为238±35nm,载药率为94%。Add antimicrobial drug ciprofloxacin hydrochloride powder in the acetic acid aqueous solution that mass fraction is 90%, make it fully dissolve with magnetic stirrer stirring, take chitosan and polyoxyethylene powder and join in the above-mentioned solution, stir to obtain uniform, Stable spinning solution, the concentration of polyethylene oxide in the spinning solution is 0.5wt%, the weight ratio of chitosan and polyethylene oxide is 90:10, and the weight ratio of antibacterial drug and polyethylene oxide is 5: 10. Electrospinning was carried out for 8 hours under the conditions of a spinning voltage of 16kv, a feeding rate of spinning solution of 0.5mL/h, a receiving distance of 20cm, an ambient temperature of 25°C and a relative humidity of 35%, and the prepared The nanofibrous membrane was placed in a desiccator filled with 25% glutaraldehyde aqueous solution, cross-linked for 24 hours, and then dried in a vacuum oven for 24 hours to remove residual solvents and cross-linking agent glutaraldehyde, and finally in the desiccator to avoid light save. As shown in Figure 2, the fiber diameter of the obtained chitosan-based drug-loaded composite antibacterial microfiber membrane is 238±35nm, and the drug-loading rate is 94%.
采用100%海藻酸钙纤维依次经过开松、梳理、铺网和水刺,梳理和铺网工艺参数为:梳理机喂入速度为0.8m/min,锡林速度为750m/min,输出纤网的速度为45m/min,铺网速度为50m/min,输出纤网的不匀率为2.5%;水刺的工艺参数为:预湿水刺头压力为25Pa,水刺头的压力分别为35Pa、35Pa、45Pa、45Pa,水刺机生产速度为10m/min,制得海藻酸钙纤维非织布2,作为组织渗透液吸收层。100% calcium alginate fibers are used to undergo opening, carding, web laying and spunlace in sequence. The process parameters of carding and web laying are: the feeding speed of the carding machine is 0.8m/min, the cylinder speed is 750m/min, and the output fiber web The speed is 45m/min, the laying speed is 50m/min, and the unevenness of the output fiber web is 2.5%. The process parameters of the spunlace are: the pressure of the pre-wet spunlace head is 25Pa, and the pressure of the spunlace head is 35Pa respectively. , 35Pa, 45Pa, 45Pa, the production speed of the spunlace machine is 10m/min, and the calcium alginate fiber nonwoven fabric 2 is prepared, which is used as the tissue permeation liquid absorption layer.
将壳聚糖基载药复合抗菌型超细纤维膜1与海藻酸钙纤维非织布2使用生物粘合剂聚丙烯酸粘合在一起,再在海藻酸钙纤维非织布2上施加聚丙烯酸酯压敏胶,最后在抗菌层面覆上离心纸后,以200m/min的速度进行分切成为一定规格的如图4所示的抗菌复合型创伤敷料。经测试,该产品具有良好的抗菌、止血、愈创的效果,同时具有良好的透气性和吸湿性。其中,抑菌圈的测定是复合敷料在细菌培养皿中放置18-24h后,从培养箱中取出后立即在室温下采用数显游标卡尺进行测试的,测得敷料的抑菌圈直径分别为金黄色葡萄球菌(SA)18mm和大肠杆菌(EC)24mm,如图5中1号样所示。敷料的吸液率达1615.2%、保液率为821.2%,防水等级为5级。The chitosan-based drug-loaded composite antibacterial microfiber membrane 1 and the calcium alginate fiber nonwoven fabric 2 are bonded together using bioadhesive polyacrylic acid, and then polyacrylic acid is applied on the calcium alginate fiber nonwoven fabric 2 Ester pressure-sensitive adhesive, and finally, after covering the antibacterial layer with centrifugal paper, it is cut at a speed of 200m/min to become an antibacterial composite wound dressing of a certain specification as shown in Figure 4. After testing, the product has good antibacterial, hemostatic and healing effects, as well as good air permeability and moisture absorption. Among them, the determination of the antibacterial zone is that after the composite dressing is placed in the bacterial culture dish for 18-24 hours, it is tested at room temperature with a digital display vernier caliper immediately after it is taken out from the incubator. Staphylococcus aureus (SA) 18mm and Escherichia coli (EC) 24mm, as shown in sample No. 1 in Fig. 5 . The liquid absorption rate of the dressing is 1615.2%, the liquid retention rate is 821.2%, and the waterproof grade is 5.
实施例2Example 2
如图1所示,为本发明的抗菌复合型创伤敷料的结构示意图,所述的抗菌复合型创伤敷料,包括从上到下依次设置的壳聚糖基载药复合抗菌型超细纤维膜1、海藻酸钙纤维非织布2和支撑保护层3。所述的支撑保护层3为带有聚丙烯酸酯压敏胶。As shown in Figure 1, it is a schematic structural view of the antibacterial composite wound dressing of the present invention, and the antibacterial composite wound dressing includes a chitosan-based drug-loaded composite antibacterial microfiber membrane 1 sequentially arranged from top to bottom , calcium alginate fiber non-woven fabric 2 and support protection layer 3. The supporting protection layer 3 is provided with polyacrylate pressure-sensitive adhesive.
所述的抗菌复合型创伤敷料的制备方法的具体步骤为:The concrete steps of the preparation method of described antibacterial composite wound dressing are:
在质量分数为90%的醋酸水溶液中加入抗菌药物盐酸环丙沙星粉末,用磁力搅拌器搅拌使其充分溶解,称取壳聚糖和聚氧化乙烯粉末加入到上述溶液中,搅拌得到均一、稳定的纺丝溶液,所述的纺丝溶液中聚氧化乙烯的浓度为0.5wt%,壳聚糖与聚氧化乙烯的重量比为90∶10,抗菌药物与聚氧化乙烯的重量比为10∶10,在纺丝电压为16kv、纺丝液给进速率为0.8mL/h、接收距离为20cm、环境温度为25℃以及相对湿度为35%的条件下进行静电纺丝8h,将制得的纳米纤维膜置于盛有25%戊二醛水溶液的干燥器中,进行交联24h后置于真空干燥箱中干燥24h,以除去残留溶剂和交联剂戊二醛,最后在干燥器中避光保存。所得的壳聚糖基载药复合抗菌超细纤维膜的纤维直径为200+30nm,载药率为94%。Add antimicrobial drug ciprofloxacin hydrochloride powder in the acetic acid aqueous solution that mass fraction is 90%, make it fully dissolve with magnetic stirrer stirring, take chitosan and polyoxyethylene powder and join in the above-mentioned solution, stir to obtain uniform, Stable spinning solution, the concentration of polyethylene oxide in the spinning solution is 0.5wt%, the weight ratio of chitosan and polyethylene oxide is 90:10, and the weight ratio of antibacterial drug and polyethylene oxide is 10: 10. Under the conditions of spinning voltage of 16kv, spinning solution feed rate of 0.8mL/h, receiving distance of 20cm, ambient temperature of 25°C and relative humidity of 35%, electrospinning was carried out for 8h, and the prepared The nanofibrous membrane was placed in a desiccator filled with 25% glutaraldehyde aqueous solution, cross-linked for 24 hours, and then dried in a vacuum oven for 24 hours to remove residual solvents and cross-linking agent glutaraldehyde, and finally in the desiccator to avoid light save. The obtained chitosan-based drug-loaded composite antibacterial ultrafine fiber membrane has a fiber diameter of 200+30nm and a drug-loading rate of 94%.
采用100%海藻酸钙纤维依次经过开松、梳理、铺网和水刺,梳理和铺网工艺参数为:梳理机喂入速度为0.7m/min,锡林速度为700m/min,输出纤网的速度为40m/min,铺网速度为45 m/min,输出纤网的不匀率为3%;水刺的工艺参数为:预湿水刺头压力为30Pa,水刺头的压力分别为40 Pa、40 Pa、45Pa、45Pa,水刺机生产速度为12m/min,制得海藻酸钙纤维非织布2,作为组织渗透液吸收层。100% calcium alginate fibers are used to go through opening, carding, web laying and spunlace in sequence. The process parameters of carding and web laying are: the feeding speed of the carding machine is 0.7m/min, the cylinder speed is 700m/min, and the output fiber web The speed is 40m/min, the laying speed is 45 m/min, and the unevenness of the output fiber web is 3%. The process parameters of the spunlace are: the pressure of the pre-wet spunlace head is 30Pa, and the pressure of the spunlace head is respectively 40 Pa, 40 Pa, 45Pa, 45Pa, the production speed of the spunlace machine is 12m/min, and the calcium alginate fiber nonwoven fabric 2 is prepared as the tissue infiltration liquid absorption layer.
将壳聚糖基载药复合抗菌型超细纤维膜1与海藻酸钙纤维非织布2使用生物粘合剂聚丙烯酸粘合在一起,再在海藻酸钙纤维非织布2上施加聚丙烯酸酯压敏胶,最后在抗菌层面覆上离心纸后,以200m/min的速度进行分切成为一定规格的抗菌复合型创伤敷料。经测试,该产品具有良好的抗菌、止血、愈创的效果,同时具有良好的透气性和吸湿性。其中,抑菌圈的测定是复合敷料在细菌培养皿中放置18-24h后,从培养箱中取出后立即在室温下采用数显游标卡尺进行测试的,测得敷料的抑菌圈直径分别为金黄色葡萄球菌(SA)15mm和大肠杆菌(EC)25mm,如图5中2号样所示。敷料的吸液率达2017.9%、保液率为777.7%,防水等级为4.5级。The chitosan-based drug-loaded composite antibacterial microfiber membrane 1 and the calcium alginate fiber nonwoven fabric 2 are bonded together using bioadhesive polyacrylic acid, and then polyacrylic acid is applied on the calcium alginate fiber nonwoven fabric 2 Ester pressure-sensitive adhesive, and finally, after covering the antibacterial layer with centrifugal paper, it is cut at a speed of 200m/min to become an antibacterial composite wound dressing of a certain specification. After testing, the product has good antibacterial, hemostatic and healing effects, as well as good air permeability and moisture absorption. Among them, the determination of the antibacterial zone is that after the composite dressing is placed in the bacterial culture dish for 18-24 hours, it is tested at room temperature with a digital display vernier caliper immediately after it is taken out from the incubator. Staphylococcus aureus (SA) 15mm and Escherichia coli (EC) 25mm, as shown in sample No. 2 in Fig. 5 . The liquid absorption rate of the dressing is 2017.9%, the liquid retention rate is 777.7%, and the waterproof grade is 4.5.
实施例3Example 3
如图1所示,为本发明的抗菌复合型创伤敷料的结构示意图,所述的抗菌复合型创伤敷料,包括从上到下依次设置的壳聚糖基载药复合抗菌型超细纤维膜1、海藻酸钙纤维非织布2和支撑保护层3。所述的支撑保护层3为带有生物胶的聚乙烯膜。As shown in Figure 1, it is a schematic structural view of the antibacterial composite wound dressing of the present invention, and the antibacterial composite wound dressing includes a chitosan-based drug-loaded composite antibacterial microfiber membrane 1 sequentially arranged from top to bottom , calcium alginate fiber non-woven fabric 2 and support protection layer 3. The supporting protective layer 3 is a polyethylene film with biological glue.
所述的抗菌复合型创伤敷料的制备方法的具体步骤为:The concrete steps of the preparation method of described antibacterial composite wound dressing are:
在质量分数为90%的醋酸水溶液中加入抗菌药物粉末盐酸莫西沙星,用磁力搅拌器搅拌使其充分溶解,称取壳聚糖和聚氧化乙烯粉末加入到上述溶液中,搅拌得到均一、稳定的纺丝溶液,所述的纺丝溶液中聚氧化乙烯的浓度为0.5wt%,壳聚糖与聚氧化乙烯的重量比为90∶10,抗菌药物与聚氧化乙烯的重量比为5∶10,在纺丝电压为16kv、纺丝液给进速率为0.5mL/h、接收距离为20cm、环境温度为25℃以及相对湿度为35%的条件下进行静电纺丝8h,将制得的纳米纤维膜置于盛有25%戊二醛水溶液的干燥器中,进行交联24h后置于真空干燥箱中干燥24h,以除去残留溶剂和交联剂戊二醛,最后在干燥器中避光保存。如图3所示,所得的壳聚糖基载药复合抗菌超细纤维膜的纤维直径为300+61nm,载药率为92%。Add antibacterial drug powder moxifloxacin hydrochloride to 90% acetic acid aqueous solution by mass fraction, stir it with a magnetic stirrer to fully dissolve it, weigh chitosan and polyethylene oxide powder and add it to the above solution, and stir to obtain a uniform, stable spinning solution, the concentration of polyoxyethylene in the spinning solution is 0.5wt%, the weight ratio of chitosan and polyoxyethylene is 90:10, and the weight ratio of antibacterial drug and polyoxyethylene is 5:10 , under the conditions of spinning voltage of 16kv, spinning solution feed rate of 0.5mL/h, receiving distance of 20cm, ambient temperature of 25°C and relative humidity of 35%, electrospinning was carried out for 8h, and the prepared nano The fiber membrane was placed in a desiccator filled with 25% glutaraldehyde aqueous solution, cross-linked for 24 hours, and then dried in a vacuum oven for 24 hours to remove residual solvents and cross-linking agent glutaraldehyde, and finally protected from light in the desiccator save. As shown in Figure 3, the fiber diameter of the obtained chitosan-based drug-loaded composite antibacterial ultrafine fiber membrane is 300+61 nm, and the drug-loading rate is 92%.
采用100%海藻酸钙纤维依次经过开松、梳理、铺网和水刺,梳理和铺网工艺参数为:梳理机喂入速度为0.9m/min,锡林速度为850m/min,输出纤网的速度为55m/min,铺网速度为50m/min,输出纤网的不匀率为3%;水刺的工艺参数为:预湿水刺头压力为25Pa,水刺头的压力分别为35Pa、35Pa、45Pa、45Pa,水刺机的生产速度为15m/min,制得海藻酸钙纤维非织布2,作为组织渗透液吸收层。100% calcium alginate fibers are used to undergo opening, carding, web laying and spunlace in sequence. The process parameters of carding and web laying are: the feeding speed of the carding machine is 0.9m/min, the cylinder speed is 850m/min, and the output fiber web The speed is 55m/min, the laying speed is 50m/min, and the unevenness of the output fiber web is 3%; the process parameters of the spunlace are: the pressure of the pre-wet spunlace head is 25Pa, and the pressure of the spunlace head is 35Pa , 35Pa, 45Pa, 45Pa, the production speed of the spunlace machine is 15m/min, and the calcium alginate fiber nonwoven fabric 2 is prepared as the tissue permeation liquid absorption layer.
将壳聚糖基载药复合抗菌型超细纤维膜1与海藻酸钙纤维非织布2使用生物粘合剂聚丙烯酸粘合在一起,再在海藻酸钙纤维非织布2上施加带有生物胶的聚乙烯膜,最后在抗菌层面覆上离心纸后,以200m/min的速度进行分切成为一定规格的抗菌复合型创伤敷料。该产品具有良好的抗菌、止血、愈创的效果,同时具有良好的透气性和吸湿性。其中,抑菌圈的测定是复合敷料在细菌培养皿中放置18-24h后,从培养箱中取出后立即在室温下采用数显游标卡尺进行测试的,测得敷料的抑菌圈直径分别为金黄色葡萄球菌(SA)22mm和大肠杆菌(EC)24mm,如图5中3号样所示。敷料的吸湿率达2052.7%、保液率为723.7%,防水等级为4级。The chitosan-based drug-loaded composite antibacterial microfiber membrane 1 and the calcium alginate fiber nonwoven fabric 2 are bonded together using bioadhesive polyacrylic acid, and then the calcium alginate fiber nonwoven fabric 2 is coated with The polyethylene film of biological glue is finally covered with centrifugal paper on the antibacterial layer, and then cut at a speed of 200m/min to become an antibacterial composite wound dressing of a certain specification. The product has good antibacterial, hemostatic and wound-healing effects, as well as good air permeability and hygroscopicity. Among them, the determination of the antibacterial zone is that after the composite dressing is placed in the bacterial culture dish for 18-24 hours, it is tested at room temperature with a digital display vernier caliper immediately after it is taken out from the incubator. Staphylococcus aureus (SA) 22mm and Escherichia coli (EC) 24mm, as shown in sample No. 3 in Fig. 5 . The moisture absorption rate of the dressing is 2052.7%, the liquid retention rate is 723.7%, and the waterproof grade is 4.
实施例4Example 4
如图1所示,为本发明的抗菌复合型创伤敷料的结构示意图,所述的抗菌复合型创伤敷料,包括从上到下依次设置的壳聚糖基载药复合抗菌型超细纤维膜1、海藻酸钙纤维非织布2和支撑保护层3。所述的支撑保护层3为聚丙烯酸酯压敏胶。As shown in Figure 1, it is a schematic structural view of the antibacterial composite wound dressing of the present invention, and the antibacterial composite wound dressing includes a chitosan-based drug-loaded composite antibacterial microfiber membrane 1 sequentially arranged from top to bottom , calcium alginate fiber non-woven fabric 2 and support protection layer 3. The supporting protective layer 3 is polyacrylate pressure-sensitive adhesive.
所述的抗菌复合型创伤敷料的制备方法的具体步骤为:The concrete steps of the preparation method of described antibacterial composite wound dressing are:
在质量分数为90%的醋酸水溶液中加入抗菌药物粉末盐酸莫西沙星,用磁力搅拌器搅拌使其充分溶解,称取壳聚糖和聚氧化乙烯粉末加入到上述溶液中,搅拌得到均一、稳定的纺丝溶液,所述的纺丝溶液中聚氧化乙烯的浓度为0.5wt%,壳聚糖与聚氧化乙烯的重量比为90∶10,抗菌药物与聚氧化乙烯的重量比为10∶10,在纺丝电压为16kv、纺丝液给进速率为0.8mL/h、接收距离为20cm、环境温度为25℃以及相对湿度为35%的条件下进行静电纺丝8h,将制得的纳米纤维膜置于盛有25%戊二醛水溶液的干燥器中,进行交联24h后置于真空干燥箱中干燥24h,以除去残留溶剂和交联剂戊二醛,最后在干燥器中避光保存。所得的壳聚糖基载药复合抗菌超细纤维膜的纤维直径为280±50nm,载药率为94%。Add antibacterial drug powder moxifloxacin hydrochloride to 90% acetic acid aqueous solution by mass fraction, stir it with a magnetic stirrer to fully dissolve it, weigh chitosan and polyethylene oxide powder and add it to the above solution, and stir to obtain a uniform, stable spinning solution, the concentration of polyoxyethylene in the spinning solution is 0.5wt%, the weight ratio of chitosan and polyoxyethylene is 90:10, and the weight ratio of antibacterial drug and polyoxyethylene is 10:10 , under the conditions of spinning voltage of 16kv, spinning solution feed rate of 0.8mL/h, receiving distance of 20cm, ambient temperature of 25°C and relative humidity of 35%, electrospinning was carried out for 8h, and the prepared nano The fiber membrane was placed in a desiccator filled with 25% glutaraldehyde aqueous solution, cross-linked for 24 hours, and then dried in a vacuum oven for 24 hours to remove residual solvents and cross-linking agent glutaraldehyde, and finally protected from light in the desiccator save. The obtained chitosan-based drug-loaded composite antibacterial ultrafine fiber membrane has a fiber diameter of 280±50 nm and a drug-loading rate of 94%.
采用100%海藻酸钙纤维依次经过开松、梳理、铺网和水刺,梳理和铺网工艺参数为:梳理机喂入速度为0.85m/min,锡林速度为800m/min,输出纤网的速度为55m/min,铺网速度为55m/min,输出纤网的不匀率为3.5%;水刺的工艺参数为:预湿水刺头压力为30Pa,水刺头的压力分别为40 Pa、40 Pa、45Pa、45Pa,水刺机的生产速度为20m/min,制得海藻酸钙纤维非织布2,作为组织渗透液吸收层。100% calcium alginate fibers are used to undergo opening, carding, web laying and spunlace in sequence. The process parameters of carding and web laying are: the feeding speed of the carding machine is 0.85m/min, the cylinder speed is 800m/min, and the output fiber web The speed is 55m/min, the laying speed is 55m/min, and the unevenness of the output fiber web is 3.5%. The process parameters of the spunlace are: the pressure of the pre-wet spunlace head is 30Pa, and the pressure of the spunlace head is 40 Pa, 40 Pa, 45Pa, 45Pa, the production speed of the spunlace machine is 20m/min, and the calcium alginate fiber nonwoven fabric 2 is prepared, which is used as the tissue permeation liquid absorption layer.
将壳聚糖基载药复合抗菌型超细纤维膜1与海藻酸钙纤维非织布2使用生物粘合剂聚丙烯酸粘合在一起,再在海藻酸钙纤维非织布2上施加聚丙烯酸酯压敏胶,最后在抗菌层面覆上离心纸后,以200m/min的速度进行分切成为一定规格的抗菌复合型创伤敷料。该产品具有良好的抗菌、止血、愈创的效果,同时具有良好的透气性和吸湿性。其中,抑菌圈的测定是复合敷料在细菌培养皿中放置18-24h后,从培养箱中取出后立即在室温下采用数显游标卡尺进行测试的,测得敷料的抑菌圈直径分别为金黄色葡萄球菌(SA)24mm和大肠杆菌(EC)25mm。其抗菌效果如图6中4号样所示。敷料的吸液率达2607.3%、保液率为757%,防水等级为5级。The chitosan-based drug-loaded composite antibacterial microfiber membrane 1 and the calcium alginate fiber nonwoven fabric 2 are bonded together using bioadhesive polyacrylic acid, and then polyacrylic acid is applied on the calcium alginate fiber nonwoven fabric 2 Ester pressure-sensitive adhesive, and finally, after covering the antibacterial layer with centrifugal paper, it is cut at a speed of 200m/min to become an antibacterial composite wound dressing of a certain specification. The product has good antibacterial, hemostatic and wound-healing effects, as well as good air permeability and hygroscopicity. Among them, the determination of the antibacterial zone is that after the composite dressing is placed in the bacterial culture dish for 18-24 hours, it is tested at room temperature with a digital display vernier caliper immediately after it is taken out from the incubator. Staphylococcus aureus (SA) 24mm and Escherichia coli (EC) 25mm. Its antibacterial effect is shown in No. 4 sample in Fig. 6. The dressing has a liquid absorption rate of 2607.3%, a liquid retention rate of 757%, and a waterproof grade of 5.
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