技术领域technical field
本发明属于医用制品技术领域，更具体地，本发明涉及一种治疗褥疮的海藻酸盐医用敷料，还涉及所述敷料的制备方法。The invention belongs to the technical field of medical products, and more specifically, the invention relates to an alginate medical dressing for treating bedsores, and also relates to a preparation method of the dressing.
背景技术Background technique
褥疮又称压迫性溃疡或压疮，是内科常见的并发症之一，是由于神经及血液循环障碍、局部组织持续缺血、营养不良而发生的软组织坏死，其发生是机体受内因和外因共同作用引起的复杂病理过程，是一种十分难治的疾病，一旦发生，疗程长，易复发，可造成从表皮到皮下组织、肌肉，甚至骨与关节的破坏，给患者带来极大的痛苦，严重者可继发感染，引起败血症而导致死亡。Bed sores, also known as pressure ulcers or pressure sores, are one of the common complications of internal medicine. They are soft tissue necrosis caused by nerve and blood circulation disorders, local tissue continuous ischemia, and malnutrition. The complex pathological process caused by the effect is a very intractable disease. Once it occurs, the course of treatment is long and it is easy to relapse, which can cause damage from the epidermis to subcutaneous tissue, muscles, and even bones and joints, bringing great pain to patients. , Severe cases can be secondary infection, causing sepsis and leading to death.
在美国，4.3％的住院患者出现褥疮并发症，其每年的医疗费用高达数十亿美元，英国也每年花费几亿英镑用于治疗褥疮患者，我国尚无此方面的完整统计数字，但因我国人口众多，卧床病人多，褥疮发病率也一直处于高数值。对于褥疮治疗，国内外都做了大量研究工作，但至今为止，仍然没有找到非常有效的治疗及护理的药物和方法。由于在如下的一系列疾病患者中，包括Ⅰ、Ⅱ、Ⅲ和Ⅳ期糖尿病患者、脑损伤后引起昏迷、半身不遂、偏瘫或截瘫患者、颈椎骨折脱位合并截瘫患者、胸椎骨折脱位合并截瘫、腰椎爆裂骨折合并截瘫患者、骨质疏松引起骨折患者、晚期肿瘤患者及其他患病治疗中较长期卧床的患者等，都有大量出现并发褥疮情况，因此,褥疮的预防治疗以及护理成为一项艰巨而重要的工作,也是护理工作中长期存在而未完全解决的一大难题。In the United States, 4.3% of hospitalized patients have decubitus complications, and its annual medical expenses are as high as billions of dollars. The UK also spends hundreds of millions of pounds a year on the treatment of decubitus patients. There is no complete statistics in this regard in our country, but because our country With a large population and a large number of bedridden patients, the incidence of bedsores has always been at a high value. For bedsore treatment, a lot of research work has been done at home and abroad, but so far, very effective medicine and method for treatment and nursing have not been found. Due to the following series of diseases in patients, including Ⅰ, Ⅱ, Ⅲ and Ⅳ diabetes patients, coma caused by brain injury, hemiplegia, hemiplegia or paraplegia patients, cervical fracture and dislocation combined with paraplegia, thoracic spine fracture and dislocation combined with paraplegia, lumbar burst Patients with fractures complicated by paraplegia, patients with fractures caused by osteoporosis, patients with advanced tumors, and other patients who have been bedridden for a long time during the treatment of other diseases, all have a large number of concurrent bedsores. Therefore, the prevention, treatment and nursing of bedsores has become a difficult and important task. It is also a long-standing problem in nursing work that has not been fully resolved.
目前，临床上治疗褥疮常用的方法包括手术治疗方法，药物治疗方法和外敷方法。手术治疗主要是采用彻底清创后皮瓣转移修复，但该方法对于许多病人并不适合；药物疗法，包括内服药和外用药，也普遍存在效果不够明显的缺点。At present, the commonly used methods for clinically treating decubitus include surgical treatment, drug treatment and external application. Surgical treatment mainly uses skin flap transfer and repair after thorough debridement, but this method is not suitable for many patients; drug therapy, including internal medicine and external medicine, also generally has the disadvantage that the effect is not obvious enough.
由于外敷方法简单易操作，且对病人的伤害最小，因此，许多临床研究也给以极大关注。传统创伤敷料包括棉纱绷带、绷带/卷装绷带、专用敷料、浸渍棉纱、豁合条带制品以及应急处理敷料杂品等，主要体现止血、防菌、防止伤口粘连和简单的包扎功能。显然，传统创伤敷料在褥疮治疗中无法满足要求。Because the external application method is simple and easy to operate, and has the least harm to patients, many clinical studies have also paid great attention. Traditional wound dressings include cotton gauze bandages, bandages/rolled bandages, special dressings, impregnated cotton yarns, loose-fitting strip products, and emergency dressing miscellaneous items, etc., mainly reflecting hemostasis, antibacterial, wound adhesion prevention and simple dressing functions. Clearly, traditional wound dressings cannot meet the requirements in the treatment of decubitus ulcers.
因此，一些研究工作也关注于褥疮专用敷料及治疗方法的开发，如：专利公开号CN1593675A提出一种褥疮换药新方法，是用2％醋酸清洗褥疮创面，再用五黄油纱布覆盖与无菌敷料包扎，取得治疗效果；专利公开号CN101461960A提出一种褥疮生物敷料，其主要成分为壳聚糖、聚六亚甲基胍、白矾、二黄粉、香油、甘泊等混合制成，用于各种创伤的消炎止血、抗菌消毒、干爽防粘连、促进皮肤组织愈合和修复；专利CN公开号102885859A提出一种治疗褥疮的药物，由煅龙骨粉、云南白药粉、75％酒精混合成糊状，治疗中先用双氧水清洗褥疮疮面，后用远红外线治疗仪照射，再将药物涂抹在疮面上起治疗作用；专利CN公开号103271794A提出一种基于褥疮创面用的生物抗菌敷贴，该敷贴包含壳聚糖、醋酸、溶菌酶、明胶、醋酸氯己定、二氧化硅气凝胶和水等成分，由透气基材、无纺人造丝、生物抗菌层、纸质隔离层组成，用于治疗褥疮创面及烧烫伤、外科手术感染。Therefore, some research work also pays attention to the development of bed sore special dressing and treatment method, as: patent publication number CN1593675A proposes a kind of new method of bed sore dressing change, is to clean the bed sore wound with 2% acetic acid, then cover with five butter gauze and aseptic Dressing to achieve therapeutic effect; Patent Publication No. CN101461960A proposes a bed sore biological dressing, the main components of which are chitosan, polyhexamethylene guanidine, alum, dihuang powder, sesame oil, glycyrrhizin, etc. Anti-inflammation and hemostasis, antibacterial and disinfection, dryness and anti-adhesion, and promotion of skin tissue healing and repair; Patent CN Publication No. 102885859A proposes a medicine for treating decubitus, which is mixed into a paste by calcined keel powder, Yunnan Baiyao powder, and 75% alcohol. In the treatment, the surface of decubitus sore is cleaned with hydrogen peroxide first, and then irradiated with a far-infrared ray therapy device, and then the medicine is applied on the sore surface to play a therapeutic effect; Patent CN Publication No. 103271794A proposes a biological antibacterial application based on decubitus wound. The patch contains chitosan, acetic acid, lysozyme, gelatin, chlorhexidine acetate, silica airgel and water, and is composed of a breathable substrate, non-woven rayon, biological antibacterial layer, and paper isolation layer. It is used in the treatment of decubitus wounds, burns, and surgical infections.
研究表明，保持褥疮创面的湿润环境，控制氧与水的透过情况，形成密闭的微环境，并且具备能够生肌消炎、促进细胞生长的条件，对于治疗褥疮至关重要。显然，上述的几项褥疮专利大部分只是简单地采用海藻酸盐、一些中西药物、简单材料的复合及简单治疗方式，没有进一步考虑如何有效设计新型敷料，通过综合考虑物理与化学、生物学的因素，一方面保持受压部位微环境的湿润，控制创面流出物，稳定创面温度变化；另一方面，控制氧和水蒸气的透过率，维持受压部位适宜的氧分压，促进微循环形成；同时考虑到抗菌与防止感染，在皮肤表面构建了一层防御细菌侵入的屏障，增强组织的抗炎能力；然后，进一步考虑利用具有促进伤口愈合、能够刺激成纤维细胞和内皮细胞的生长及促进角质细胞增殖的成分，达到强化伤口愈合与提升治疗效果的目的。Studies have shown that maintaining a moist environment on bedsore wounds, controlling the penetration of oxygen and water, forming a closed microenvironment, and having conditions that can produce muscle, reduce inflammation, and promote cell growth are essential for the treatment of bedsores. Obviously, most of the above-mentioned bedsore patents simply use alginate, some Chinese and Western medicines, compounding of simple materials and simple treatment methods, without further consideration of how to effectively design new dressings. By comprehensively considering the physical, chemical and biological aspects factors, on the one hand, keep the microenvironment moist at the pressured part, control the wound effluent, and stabilize the temperature change of the wound; Formation; at the same time, taking into account antibacterial and anti-infection, a layer of barrier against bacterial invasion is built on the skin surface, and the anti-inflammatory ability of the tissue is enhanced; And ingredients that promote keratinocyte proliferation to achieve the purpose of strengthening wound healing and improving therapeutic effect.
目前，我国市场具有自主知识产权的用于治疗褥疮的高端敷料还很少，而能够综合考虑到维持褥疮创面湿润与氧、水分微环境，采用高效抗菌防感染并且进一步考虑应用到能够加速伤口愈合的材料来制备现代褥疮敷料，几乎是空白。因此，研究新型的高端褥疮敷料制备技术与制备方法，具有极其重要的意义。At present, there are very few high-end dressings for the treatment of bedsores with independent intellectual property rights in the Chinese market, but they can comprehensively consider maintaining the microenvironment of bedsore wounds moist, oxygen and moisture, adopt high-efficiency antibacterial and anti-infection, and further consider the application to accelerate wound healing. The materials used to prepare modern decubitus dressings are almost blank. Therefore, it is of great significance to study new high-end bedsore dressing preparation technology and preparation method.
发明内容Contents of the invention
本发明的目的是提供一治疗褥疮的海藻酸盐敷料及其制备方法，其治疗效果好，制备方便，便于推广。The purpose of the present invention is to provide an alginate dressing for treating decubitus and its preparation method, which has good therapeutic effect, convenient preparation and popularization.
为实现上述目的，本发明采取的技术方案为：In order to achieve the above object, the technical scheme that the present invention takes is:
一种治疗褥疮的海藻酸盐医用敷料，该敷料具有双层复合结构，即由底层和面层构成，底层为海藻酸盐复合膜层，面层为天然橡胶膜层。The invention discloses an alginate medical dressing for treating decubitus. The dressing has a double-layer composite structure, that is, it is composed of a bottom layer and a surface layer. The bottom layer is an alginate composite film layer, and the surface layer is a natural rubber film layer.
1.所述天然橡胶膜层为环氧化程度达到30～40％的环氧化天然橡胶材料薄膜，该膜的厚度为0.04～0.1毫米；所述海藻酸盐复合膜层是由海藻酸钠、聚丙烯酸钠、鲨鱼胶原蛋白、猪皮胶原蛋白、壳聚糖季铵盐、碱性成纤维细胞生长因子(bFGF)几种材料构成的纤维膜，该膜的厚度为1～5毫米；所述纤维膜是由纤维丝叠加排列构成，该纤维丝具有芯、壳结构，其中，壳层由海藻酸钠、聚丙烯酸钠、鲨鱼胶原蛋白、猪皮胶原蛋白材料构成；芯层由壳聚糖季铵盐及生长因子材料构成，纤维膜表面涂覆有含氯化钙和氯化锌的材料层和经过炮制的中药白芨、赤芍、血竭、土木鳖、紫草的提取物的材料层。1. described natural rubber film layer is the epoxidized natural rubber material film that epoxidation degree reaches 30～40%, and the thickness of this film is 0.04～0.1 millimeter; Described alginate composite film layer is made of sodium alginate , sodium polyacrylate, shark collagen, pigskin collagen, chitosan quaternary ammonium salt, basic fibroblast growth factor (bFGF) several materials composed of fibrous membrane, the thickness of the membrane is 1 to 5 mm; The fibrous membrane is composed of fiber filaments superimposed and arranged. The fiber filaments have a core and shell structure, wherein the shell layer is made of sodium alginate, sodium polyacrylate, shark collagen, and pigskin collagen materials; the core layer is made of chitosan Composed of quaternary ammonium salts and growth factor materials, the surface of the fiber membrane is coated with a material layer containing calcium chloride and zinc chloride, and a material layer of processed Chinese medicine extracts of Bletilla striata, red peony root, blood jellyfish, common soft-shelled turtle, and comfrey .
一种治疗褥疮的海藻酸盐医用敷料的制备方法，包括如下步骤：A preparation method for an alginate medical dressing for treating decubitus, comprising the steps of:
A、制备鲨鱼胶原蛋白溶液A. Preparation of Shark Collagen Solution
取鲨鱼皮与骨的混合物干品，粉碎后加入一定量NaOH溶液浸泡、沥干，加入石油醚浸泡后、沥干，再加入乙酸溶液提取、离心后，取上清液加硫酸钠溶液沉淀，沉淀物经蒸馏水洗涤、冷冻干燥，获得鲨鱼皮和骨混合胶原蛋白，将其溶解于一定浓度的乙酸溶液，获得鲨鱼胶原蛋白溶液。Take the dry product of the mixture of shark skin and bone, crush it, add a certain amount of NaOH solution to soak, drain, add petroleum ether to soak, drain, add acetic acid solution to extract, centrifuge, take the supernatant and add sodium sulfate solution to precipitate, The precipitate is washed with distilled water and freeze-dried to obtain shark skin and bone mixed collagen, which is dissolved in a certain concentration of acetic acid solution to obtain a shark collagen solution.
B、制备同轴静电纺丝外层溶液B. Preparation of coaxial electrospinning outer layer solution
取步骤A获得的溶液，加入海藻酸钠、聚丙烯酸钠、猪皮胶原蛋白，搅拌混合均匀，得到一种含海藻酸盐混合物的复合溶液；Take the solution obtained in step A, add sodium alginate, sodium polyacrylate, and pigskin collagen, stir and mix evenly, and obtain a composite solution containing an alginate mixture;
C、制备同轴静电纺丝芯层溶液C. Preparation of coaxial electrospinning core layer solution
将壳聚糖季铵盐溶解于蒸馏水中，加入碱性成纤维细胞生长因子(bFGF)，搅拌均匀，得到一种含有壳聚糖季铵盐和生长因子的复合溶液；Chitosan quaternary ammonium salt is dissolved in distilled water, basic fibroblast growth factor (bFGF) is added, and stirred evenly to obtain a composite solution containing chitosan quaternary ammonium salt and growth factor;
D、纺丝D. Spinning
采用同轴静电纺丝法，让步骤B得到的海藻酸盐复合溶液作为同轴静电纺丝的外层溶液，让步骤C得到的含有壳聚糖季铵盐和生长因子的复合溶液作为同轴静电纺丝的内层溶液，进行同轴纺丝，得到以海藻酸盐为主体的带有核壳双层结构的纤维丝及由纤维丝构成的纤维膜；Using the coaxial electrospinning method, the alginate composite solution obtained in step B is used as the outer layer solution of coaxial electrospinning, and the composite solution containing chitosan quaternary ammonium salt and growth factors obtained in step C is used as the coaxial electrospinning solution. The inner layer solution of electrospinning is coaxially spun to obtain a fiber filament with a core-shell double-layer structure mainly composed of alginate and a fiber membrane composed of the fiber filament;
E、交联E. Cross-linking
将步骤D得到的纤维膜浸入含氯化物混合物溶液中若干时间，取出后在热风条件下干燥若干时间，得到交联海藻酸盐复合物；Immerse the fibrous membrane obtained in step D in the chloride-containing mixture solution for a certain period of time, take it out and dry it under hot air conditions for a certain period of time to obtain a cross-linked alginate composite;
F、浸渍F. Dipping
将步骤E得到的交联海藻酸盐复合物浸入含白芨、赤芍、血竭、土木鳖、紫草成分的复合中药水煮液中放置若干时间，取出在热风条件下干燥一定时间，得到含中药成分的交联海藻酸盐复合物；Immerse the cross-linked alginate compound obtained in step E into the compound Chinese medicine boiled liquid containing bletilla striata, red peony root, dried rhizome, common soft-shelled turtle and comfrey for a certain period of time, take it out and dry it under hot air for a certain period of time to obtain a compound containing Cross-linked alginate complex of traditional Chinese medicine ingredients;
G、制备环氧化天然橡胶薄膜G, preparation of epoxidized natural rubber film
采用流延法制备厚度为0.04～0.1毫米的环氧化天然橡胶薄膜；The epoxidized natural rubber film with a thickness of 0.04 to 0.1 mm is prepared by casting method;
H、复合H. Composite
将步骤F获得的复合物与步骤G获得的环氧化天然橡胶薄膜复合，即得到所述的治疗褥疮的海藻酸盐敷料。Composite the compound obtained in step F with the epoxidized natural rubber film obtained in step G to obtain the alginate dressing for treating decubitus.
优选的步骤A中鲨鱼皮和骨的混合物干品为鲨鱼皮与鲨鱼软骨的比例分别为6～7:4～3混合物，经过干燥至含水量低于5％的干品；该干品粉碎为细度20-50目后，加入1:15质量的0.1N/L NaOH溶液，8℃温度下浸泡5小时，取出沥干；加入1:10的石油醚，8℃温度下浸泡12小时，用蒸馏水洗涤后沥干；再加1:10的2.5％-3.5％的乙酸溶液并在8℃下，搅拌速度为300～500rpm搅拌48小时；经过40000转/min离心，取上清液加入1mol/L硫酸钠，经过沉淀、过滤、蒸馏水洗涤，再加1:10的2.5％-3.5％的乙酸溶液溶解，采用截留分子量为100kDa超滤膜超滤，滤液冷冻干燥，获得鲨鱼皮和软骨混合胶原蛋白，再取2％乙酸溶液溶解，配成含混合胶原蛋白浓度为0.3％的溶液The dry product of the mixture of shark skin and bone in the preferred step A is a mixture of shark skin and shark cartilage in a ratio of 6 to 7:4 to 3, which is dried to a water content of less than 5%; the dry product is pulverized into After the fineness is 20-50 mesh, add 1:15 mass of 0.1N/L NaOH solution, soak at 8°C for 5 hours, take it out and drain; add 1:10 petroleum ether, soak at 8°C for 12 hours, use Wash with distilled water and drain; add 1:10 2.5%-3.5% acetic acid solution and stir for 48 hours at 8°C with a stirring speed of 300-500rpm; after centrifugation at 40,000 rpm, take the supernatant and add 1mol/ L sodium sulfate, precipitated, filtered, washed with distilled water, dissolved in 2.5%-3.5% acetic acid solution at 1:10, ultrafiltered with an ultrafiltration membrane with a molecular weight cut-off of 100kDa, and the filtrate was freeze-dried to obtain shark skin and cartilage mixed collagen Protein, then take 2% acetic acid solution to dissolve, and make a solution containing mixed collagen with a concentration of 0.3%
优选的步骤B中所述的海藻酸钠加入量为0.4～0.8％，海藻酸钠与聚丙烯酸钠的重量比为1:0.2～0.4，海藻酸钠与猪皮胶原的重量比为1:0.05～0.08，该猪皮胶原蛋白为分子量在10D至30D的低分子胶原蛋白，搅拌速度为300～500rpm，搅拌20分钟。Preferably, the amount of sodium alginate added in step B is 0.4-0.8%, the weight ratio of sodium alginate to sodium polyacrylate is 1:0.2-0.4, and the weight ratio of sodium alginate to pigskin collagen is 1:0.05 ~0.08, the pigskin collagen is a low-molecular collagen with a molecular weight of 10D to 30D, and the stirring speed is 300-500 rpm for 20 minutes.
优选的步骤C中所述的壳聚糖季铵盐和生长因子复合溶液中的壳聚糖季铵盐是壳聚糖的季铵化改性产物，含量为0.3～0.5％；碱性成纤维细胞生长因子(bFGF)含量为0.001％，搅拌速度为300～500rpm，搅拌10分钟。The chitosan quaternary ammonium salt described in the preferred step C and the chitosan quaternary ammonium salt in the growth factor composite solution is a quaternized modified product of chitosan, and the content is 0.3% to 0.5%; The content of cell growth factor (bFGF) is 0.001%, the stirring speed is 300-500 rpm, and stirring is carried out for 10 minutes.
优选的步骤D中所述的同轴静电纺丝法，是以步骤B中所得到的海藻酸盐复合溶液作为纺丝的外层溶液，以步骤C中所得到的含壳聚糖季铵盐和生长因子复合溶液作为纺丝的内层溶液，在电压为30kV、固定阳极与阴极之间的距离为18cm，温度为28～30℃的条件下，进行同轴静电纺丝，在接收板上得到淡黄色、带有核壳结构的纤维丝并由纤维丝构成的海藻酸盐纤维膜。The coaxial electrospinning method described in the preferred step D uses the alginate composite solution obtained in the step B as the outer layer solution of spinning, and the chitosan-containing quaternary ammonium salt obtained in the step C and growth factor complex solution as the inner layer solution of spinning, under the conditions of voltage of 30kV, fixed distance between anode and cathode of 18cm, and temperature of 28-30°C, coaxial electrospinning is carried out on the receiving plate A pale yellow alginate fiber membrane with a core-shell structure and composed of fiber filaments was obtained.
优选的步骤E中所述的氯化物混合物溶液为含3％氯化钙与0.5％氯化锌的混合水溶液，浸入后放置时间为20至30分钟，然后取出，在35～40℃热空气中干燥，干燥时间为1～2小时。Preferably, the chloride mixture solution described in step E is a mixed aqueous solution containing 3% calcium chloride and 0.5% zinc chloride, and the soaking time is 20 to 30 minutes, then taken out, and placed in hot air at 35 to 40°C Drying, the drying time is 1-2 hours.
优选的步骤F中所述复合中药水煮液，是中药白芨、赤芍、血竭、土木鳖、紫草各10克，加入120克水，浸泡20分钟后，煮沸25分钟，倒出液体，药渣再加水100克，再次煮沸20分钟，合并两次液体，加水定容200毫升，成为复合中药水煮液；交联海藻酸盐复合物浸入中药水煮液后放置时间为2分钟，然后取出干燥，在35～40℃热空气中干燥，干燥时间为1～2小时。The compound Chinese medicine boiled liquid described in the preferred step F is 10 grams each of the Chinese medicines Bletilla striata, Radix Paeoniae Rubra, Radix Sinensis, Turtle, and Comfrey, add 120 grams of water, soak for 20 minutes, boil for 25 minutes, pour out the liquid, Add 100 grams of water to the dregs of the medicine, boil again for 20 minutes, combine the two liquids, add water to make up 200 ml, and become a compound Chinese medicine boiled liquid; the cross-linked alginate compound is immersed in the traditional Chinese medicine boiled liquid and left for 2 minutes, then Take it out and dry it in hot air at 35-40°C for 1-2 hours.
优选的步骤G中所述的环氧化天然橡胶薄膜为环氧化程度为30～40％的环氧化天然橡胶，溶解在四氢呋喃中，配制成1％溶液，然后通过流延法涂布在洁净不粘纸上，经过68～70℃的热空气干燥，干燥时间为40分钟，获得的厚度为0.04～0.1毫米的环氧化天然橡胶薄膜。The epoxidized natural rubber film described in the preferred step G is an epoxidized natural rubber with an epoxidized degree of 30 to 40%, dissolved in tetrahydrofuran, prepared as a 1% solution, and then coated on On clean non-stick paper, after drying with hot air at 68-70°C for 40 minutes, an epoxidized natural rubber film with a thickness of 0.04-0.1 mm is obtained.
本发明所用的鲨鱼皮与鲨鱼软骨是目前市场上销售的产品，例如由北海市臻美达海洋生物制品有限公司以商品名鲨鱼软骨粉和鲨鱼皮粉销售的产品。The shark skin and shark cartilage used in the present invention are products currently sold on the market, such as products sold under the trade name shark cartilage powder and shark skin powder by Beihai Zhenmeida Marine Biological Products Co., Ltd.
本发明使用的超滤膜是目前市场上销售的产品，例如由北京陶氏超滤膜公司供应的以商品名SFP2680超滤膜或广州超禹膜分离技术有限公司以商品名CYG90S聚砜超滤膜销售的产品。The ultrafiltration membrane that the present invention uses is the product sold on the market at present, for example supplied by Beijing Dow Ultrafiltration Membrane Co. Film sales of products.
如果本发明使用的鲨鱼软骨含量低于30％时，则会使敷料的抗氧化、抗自由基及消炎作用降低；如果本发明使用的鲨鱼软骨含量高于40％时，则会出现血管抑制因子含量过高，不利伤口愈合。因此，本发明使用的鲨鱼软骨含量为30～40％是合适的，优选地是32～38％，更优选地是34～36％。If the content of shark cartilage used in the present invention is lower than 30%, the anti-oxidation, anti-free radical and anti-inflammatory effects of the dressing will be reduced; if the content of shark cartilage used in the present invention is higher than 40%, vascular inhibitory factors will appear If the content is too high, it is not conducive to wound healing. Therefore, the content of shark cartilage used in the present invention is suitable to be 30-40%, preferably 32-38%, more preferably 34-36%.
本发明使用的海藻酸钠为是目前市场上销售的产品，例如由青岛黄海生物制药有限责任公司以商品名海藻酸钠销售的产品或由连云港天天海藻工业有限公司以商品名海藻酸钠销售的产品。The sodium alginate used in the present invention is a product currently on the market, such as a product sold under the trade name sodium alginate by Qingdao Huanghai Biopharmaceutical Co., Ltd. or a product sold under the trade name sodium alginate by Lianyungang Tiantian Seaweed Industry Co., Ltd. product.
本发明使用的聚丙烯酸钠是目前市场上销售的产品，例如由山东科宇水处理有限公司以商品名聚丙烯酸钠或由焦作市泰烽精细化工有限公司以商品名聚丙烯酸钠销售的产品。The sodium polyacrylate used in the present invention is a product currently on the market, such as a product sold by Shandong Keyu Water Treatment Co., Ltd. under the trade name sodium polyacrylate or by Jiaozuo Taifeng Fine Chemical Co., Ltd. under the trade name sodium polyacrylate.
本发明使用的猪皮胶原蛋白是由暨南大学生物医学工程研究所专利技术(CN1470640)制备的猪皮胶原蛋白。The pigskin collagen used in the present invention is the pigskin collagen prepared by the patented technology (CN1470640) of the Institute of Biomedical Engineering of Jinan University.
如果本发明使用的海藻酸钠含量低于0.4％时，则会使后续的静电纺丝无法进行；如果本发明使用的海藻酸钠含量高于0.8％时，则会出现溶解不容易问题。因此，本发明使用的海藻酸钠含量为0.4～0.8％是合适的，优选地是0.5～0.8％，更优选地是0.6～0.7％。If the content of sodium alginate used in the present invention is lower than 0.4%, the subsequent electrospinning cannot be performed; if the content of sodium alginate used in the present invention is higher than 0.8%, the problem of difficulty in dissolution will occur. Therefore, the content of sodium alginate used in the present invention is suitable to be 0.4-0.8%, preferably 0.5-0.8%, more preferably 0.6-0.7%.
如果本发明使用的聚丙烯酸钠含量低于0.2时，则会制备的敷料的吸水性受到不利影响；如果本发明使用的聚丙烯酸钠含量高于0.4，则会使后续的胶原蛋白的溶解受影响。因此，本发明使用的聚丙烯酸钠含量为0.2～0.4是合适的，优选地是0.3～0.4％，更优选地是0.4％。If the sodium polyacrylate content used in the present invention is lower than 0.2, the water absorption of the dressing prepared will be adversely affected; if the sodium polyacrylate content used in the present invention is higher than 0.4, the dissolution of subsequent collagen will be affected . Therefore, the content of sodium polyacrylate used in the present invention is suitable to be 0.2-0.4, preferably 0.3-0.4%, more preferably 0.4%.
如果本发明使用的猪皮胶原蛋白含量低于0.05时，则无法起到护理皮肤及伤口的作用；如果本发明使用的胶原蛋白含量高于0.08时，则会出现影响静电纺丝的问题。因此，本发明使用的胶原蛋白含量为0.05～0.08是合适的，优选地是0.06～0.08，更优选地是0.07～0.08。If the collagen content of the pigskin used in the present invention is lower than 0.05, it will not be able to care for the skin and wounds; if the collagen content used in the present invention is higher than 0.08, there will be problems affecting electrospinning. Therefore, the collagen content used in the present invention is suitable to be 0.05-0.08, preferably 0.06-0.08, more preferably 0.07-0.08.
本发明使用的壳聚糖季铵盐是目前市场上销售的产品，例如由南通绿神生物工程有限公司以商品名壳聚糖季铵盐销售的产品。The chitosan quaternary ammonium salt used in the present invention is a product currently sold on the market, such as a product sold under the trade name chitosan quaternary ammonium salt by Nantong Lvshen Biological Engineering Co., Ltd.
本发明使用的bFGF生长因子是由暨南大学生物工程研究所专利技术(CN1500809)制备的bFGF生长因子。The bFGF growth factor used in the present invention is the bFGF growth factor prepared by the patented technology (CN1500809) of the Institute of Bioengineering of Jinan University.
如果本发明使用的壳聚糖季铵盐含量低于0.3％时，则会使敷料无法体现好的抗菌消炎作用；如果本发明使用的壳聚糖季铵盐含量高于0.5％时，则影响到生长因子发挥正常效能。因此，本发明使用的壳聚糖季铵盐含量为0.3～0.5％是合适的，优选地是0.4～0.5％。If the chitosan quaternary ammonium content that the present invention uses is lower than 0.3%, then can make dressing can't embody good antibacterial and anti-inflammatory effect; If the chitosan quaternary ammonium content that the present invention uses is higher than 0.5%, then influence To the growth factor to play a normal role. Therefore, the content of chitosan quaternary ammonium salt used in the present invention is suitable to be 0.3-0.5%, preferably 0.4-0.5%.
本发明使用的氯化钙为是目前市场上销售的产品，例如由山东东信化学工业有限公司以商品名氯化钙销售的产品或由潍坊市神州化学有限公司以商品名氯化钙销售的产品。Calcium chloride used in the present invention is a product currently sold on the market, such as a product sold by Shandong Dongxin Chemical Industry Co., Ltd. with a trade name of calcium chloride or a product sold by Weifang Shenzhou Chemical Co., Ltd. with a trade name of calcium chloride .
本发明使用的氯化锌是目前市场上销售的产品，例如由河北省晋州市冀田锌业有限公司以商品名氯化锌或由广州试剂公司以商品名氯化锌销售的产品。The zinc chloride that the present invention uses is the product sold on the market at present, for example by the product that trade name zinc chloride is sold by Guangzhou reagent company with trade name zinc chloride by Ji Tian Zinc Co., Ltd., Jinzhou City, Hebei Province.
如果本发明中纤维膜浸入混合液中的时间低于20分钟时，则会使纤维膜因交联不足而影响敷料的性能；如果纤维膜浸入混合液中的时间高于30分钟时，则会因交联过度而降低敷料的吸液效果。因此，本发明采用的浸入放置时间为20至30分钟，最优选是25分钟。If the time of fiber membrane immersed in the mixed solution among the present invention is lower than 20 minutes, then will make fiber membrane affect the performance of dressing because of cross-linking deficiency; If the time of fiber membrane immersed in mixed solution is higher than 30 minutes, then will Reduced fluid absorption of dressings due to over-crosslinking. Therefore, the soaking time used in the present invention is 20 to 30 minutes, most preferably 25 minutes.
本发明使用的中草药白芨、赤芍、血竭、土木鳖、紫草是目前市场上销售的产品，例如由广州南北行中药饮片有限公司以商品名白芨、赤芍、血竭、土木鳖、紫草销售的产品。The Chinese herbal medicine Bletilla striata, Radix Paeoniae Rubra, Rhizoma Bletilla striata, Radix Radix Radix Radix Rubrae, Radix Echinacea, Zicao that are used in the present invention are the products sold on the market at present, such as by Guangzhou Nanbeihang Traditional Chinese Medicine Pieces Co., Ltd. Grass products for sale.
本发明使用的环氧化天然橡胶是由中国热带农业科学院产品加工研究所专利技术(CN101654488)生产的环氧化天然橡胶。The epoxidized natural rubber used in the present invention is the epoxidized natural rubber produced by the patented technology (CN101654488) of the Product Processing Research Institute of the Chinese Academy of Tropical Agricultural Sciences.
如果本发明使用的环氧化天然橡胶的环氧化程度低于30％时，则会影响敷料的密闭效果；如果本发明使用的环氧化天然橡胶的环氧化程度高于40％时，则会出现薄膜透气性过低，水蒸气不容易散发，影响敷料对伤口愈合的促进作用。因此，本发明使用的环氧化天然橡胶的环氧化程度为30～40％是合适的，优选地是31～37％，更优选地是32～35％。If the degree of epoxidation of the epoxidized natural rubber used in the present invention is lower than 30%, it will affect the sealing effect of the dressing; if the degree of epoxidized natural rubber used in the present invention is higher than 40%, It will appear that the air permeability of the film is too low, and the water vapor is not easy to dissipate, which will affect the promoting effect of the dressing on wound healing. Therefore, the epoxidation degree of the epoxidized natural rubber used in the present invention is suitable to be 30-40%, preferably 31-37%, more preferably 32-35%.
在以上步骤中，在热空气干燥设备中干燥的物品达到水含量低于以重量计5％以下。在以上步骤中使用的离心设备、干燥设备是本技术领域里通常使用的、在目前市场上销售的产品。所述物品的水含量是采用干燥称重方法测定得到的。本发明使用的静电纺丝设备是采用暨南大学生物医学工程研究所专利(CN103060932A)技术制造的转鼓式静电纺丝机。In the above steps, the article dried in the hot air drying equipment reaches a water content below 5% by weight. Centrifugal equipment and drying equipment used in the above steps are products commonly used in the art and sold on the market at present. The water content of the article is measured by dry weighing method. The electrospinning equipment used in the present invention is a drum type electrospinning machine manufactured by the patent (CN103060932A) of the Institute of Biomedical Engineering of Jinan University.
本发明的有益效果是：The beneficial effects of the present invention are:
①采用鲨鱼胶原蛋白作为敷料的组成部分，既利用鲨鱼皮胶原的良好抗氧化、抗自由基和消炎与促进褥疮创面愈合作用，又利用到鲨鱼软骨胶原与多糖的血管生长抑制因子活性成分，控制创面在愈合过程不会产生组织增生，无明显的疤痕形成。① Shark collagen is used as a component of the dressing, which not only utilizes the good anti-oxidation, anti-free radical and anti-inflammatory effects of shark skin collagen and promotes the healing of decubitus wounds, but also uses the active ingredients of angiogenesis inhibitory factors of shark cartilage collagen and polysaccharides to control During the wound healing process, there will be no tissue hyperplasia and no obvious scar formation.
②采用海藻酸钠与聚丙烯酸钠作为敷料的主体部分，既利用海藻酸盐的良好吸液性能与促进肌肤生长作用，又利用聚丙烯酸钠的高吸湿性，保证创面一直处于湿润环境，有益于创面的愈合。同时，也进一步利用猪皮低分子胶原蛋白，起到促进创面健康愈合的作用。② Sodium alginate and sodium polyacrylate are used as the main part of the dressing, which not only utilizes the good liquid absorption performance of alginate and the effect of promoting skin growth, but also utilizes the high hygroscopicity of sodium polyacrylate to ensure that the wound is always in a moist environment, which is beneficial to Wound healing. At the same time, pigskin low-molecular-weight collagen is further used to promote the healthy healing of wounds.
③利用同轴纺丝技术，将壳聚糖季铵盐及生长因子作为内核层，产生缓释作用，既起到抗菌消炎，又能够促进肌肤生长；采用静电纺丝技术，通过海藻酸盐与鲨鱼胶原、低分子胶原的纺丝成纤维，控制纤维结构，调节透气性，并形成良好的阻隔微生物、粉尘的性能。此外，制备的纳米纤维具有多功能性，具备高达100m2/g以上的比表面积，有很好的吸液吸湿性，可有效地吸收伤口的流出物，能够保证创面的生物环境，有利于创面的愈合，减轻病人的痛苦。③Using coaxial spinning technology, chitosan quaternary ammonium salt and growth factors are used as the inner core layer to produce slow release, which can not only play an antibacterial and anti-inflammatory role, but also promote skin growth; using electrospinning technology, through alginate and Shark collagen and low-molecular-weight collagen are spun into fibers to control the fiber structure, adjust the air permeability, and form a good performance of blocking microorganisms and dust. In addition, the prepared nanofibers are multifunctional, have a specific surface area of over 100m2 /g, have good liquid absorption and hygroscopicity, can effectively absorb wound exudates, can ensure the biological environment of the wound surface, and are beneficial to the wound surface. healing and relieve the pain of the patient.
④采用锌与钙二价离子结合，作为交联剂，使部分海藻酸钠通过离子交换，生成二价离子交联络合物，使敷料具有良好的物理机械性能与水不溶解性能，同时，利用敷料覆盖创面与接触，产生离子交换，释放出锌离子，锌离子在创面渗透，加快表皮细胞移动，并提高细胞的再生能力，促进创面愈合。④ Combining zinc and calcium divalent ions as a cross-linking agent, so that part of the sodium alginate is ion-exchanged to form a divalent ion cross-linking complex, so that the dressing has good physical and mechanical properties and water insolubility. At the same time, using The dressing covers the wound surface and contacts, produces ion exchange, releases zinc ions, zinc ions penetrate the wound surface, accelerates the movement of epidermal cells, improves the regeneration ability of cells, and promotes wound healing.
⑤采用含有中草药白芨、赤芍、血竭、土木鳖、紫草成分的复合中药水煮液浸渍敷料，利用这些中药良好的收敛止血、消肿散瘀、活血生肌、疗疮解毒与促进创面愈合生长的功效，进一步提高创面愈合速度。⑤Impregnate the dressing with the compound Chinese medicine boiled liquid containing the Chinese herbal medicines Bletilla striata, Radix Paeoniae Rubra, Dried Blood, Turtle, and Comfrey. Use these Chinese medicines to astringe and stop bleeding, reduce swelling and blood stasis, promote blood circulation and granulation, treat sores and detoxify, and promote wound healing. The effect of healing growth further improves the speed of wound healing.
⑥研究表明，应用密闭性敷料可有效隔绝外界细菌的侵入，大幅降低感染率，并且防止感染创面细菌传播而造成医院交叉感染，同时，密闭环境贮留的创面渗出液中含有丰富的巨噬细胞、淋巴细胞、单核细胞等，有利于白细胞介导的宿主吞噬细胞发挥作用，增强局部杀菌与组织再生能力。本发明利用环氧化橡胶的良好气密性能，具有调解氧气与水蒸气渗透速率的作用，采用厚度为0.04～0.1毫米的环氧化天然橡胶薄膜作为最外层，维持创面的相对密闭与湿润环境，增强白细胞功能，加速创面的上皮化、肉芽形成、纤维素和坏死物质的降解，抑制细菌的繁殖和扩散，从而极大地缩短创面愈合的时间。⑥ Studies have shown that the application of airtight dressings can effectively isolate the invasion of external bacteria, greatly reduce the infection rate, and prevent the spread of bacteria on infected wounds and cause hospital cross-infection. At the same time, the wound exudate stored in an airtight environment is rich in macrophages Cells, lymphocytes, monocytes, etc., are conducive to the role of host phagocytes mediated by white blood cells, and enhance local sterilization and tissue regeneration capabilities. The invention utilizes the good airtight performance of epoxidized rubber, which has the effect of mediating the permeation rate of oxygen and water vapor, and adopts an epoxidized natural rubber film with a thickness of 0.04-0.1 mm as the outermost layer to maintain the relative airtightness and moisture of the wound surface environment, enhance the function of white blood cells, accelerate the epithelialization of wounds, granulation formation, degradation of cellulose and necrotic substances, and inhibit the reproduction and spread of bacteria, thereby greatly shortening the time of wound healing.
本发明制备的敷料是一种复合物，具有现代敷料的机械、物理和化学、生物学性能，既有天然生物材料的良好生物相容性，又有合成生物材料的可控生长调解、良好吸湿性与消炎、抗菌性，可以改善伤口局部的血流供应，促进组织生长，加快创面愈合，显示出良好的多功能性，同时具有良好的孔隙度，手感柔软舒适，顺应性好，使用方便，适合在现代生物医学领域，特别是在褥疮治疗与护理等领域使用，本发明制备的海藻酸盐敷料可应用于包括Ⅰ、Ⅱ、Ⅲ和Ⅳ期糖尿病患者、脑损伤后引起昏迷、半身不遂、偏瘫或截瘫患者、颈椎骨折脱位合并截瘫患者、胸椎骨折脱位合并截瘫、腰椎爆裂骨折合并截瘫患者、骨质疏松引起骨折患者、晚期肿瘤患者及其他患病治疗中较长期卧床的患者等并发褥疮的治疗与护理等用途。The dressing prepared by the present invention is a compound, which has the mechanical, physical, chemical and biological properties of modern dressings, and not only has good biocompatibility of natural biological materials, but also has controllable growth mediation and good moisture absorption of synthetic biological materials. anti-inflammatory, antibacterial, can improve the local blood supply of the wound, promote tissue growth, accelerate wound healing, showing good versatility, good porosity, soft and comfortable feel, good compliance, easy to use, It is suitable for use in the field of modern biomedicine, especially in the fields of bed sore treatment and care. The alginate dressing prepared by the present invention can be applied to patients with diabetes mellitus in stages I, II, III and IV, coma, hemiplegia, and hemiplegia caused by brain injury. Or paraplegic patients, patients with cervical fracture and dislocation combined with paraplegia, patients with thoracic spine fracture and dislocation combined with paraplegia, patients with lumbar burst fracture combined with paraplegia, patients with fractures caused by osteoporosis, patients with advanced tumors, and other patients who have been bedridden for a long time during the disease treatment and nursing purposes.
附图说明Description of drawings
图1为本发明实施例海藻酸盐医用敷料的结构示意图。Fig. 1 is a schematic structural view of an alginate medical dressing according to an embodiment of the present invention.
图2为本发明实施例纤维丝的结构示意图。Fig. 2 is a schematic diagram of the structure of the fiber filament of the embodiment of the present invention.
具体实施方式Detailed ways
实施例1Example 1
2.如图1、图2所示，一种治疗褥疮的海藻酸盐医用敷料，该敷料具有双层复合结构，即由底层和面层构成，底层为海藻酸盐复合膜层2，面层为天然橡胶膜层1。天然橡胶膜层1为环氧化程度达到30～40％的环氧化天然橡胶材料薄膜，该膜的厚度为0.04～0.1毫米；海藻酸盐复合膜层2是由海藻酸钠、聚丙烯酸钠、鲨鱼胶原蛋白、猪皮胶原蛋白、壳聚糖季铵盐、碱性成纤维细胞生长因子(bFGF)几种材料构成的纤维膜，该膜的厚度为1～5毫米；纤维膜是由纤维丝叠加排列构成，该纤维丝具有芯4、壳3结构，其中壳层由海藻酸钠、聚丙烯酸钠、鲨鱼胶原蛋白、猪皮胶原蛋白材料构成；芯层由壳聚糖季铵盐及生长因子材料构成，纤维膜表面涂覆有含氯化钙和氯化锌的材料层和经过炮制的中药白芨、赤芍、血竭、土木鳖、紫草的提取物的材料层。2. As shown in Figure 1 and Figure 2, a kind of alginate medical dressing for treating decubitus, this dressing has a double-layer composite structure, promptly is made of bottom layer and surface layer, bottom layer is alginate composite film layer 2, surface layer It is the natural rubber film layer 1. The natural rubber film layer 1 is an epoxidized natural rubber material film whose epoxidation degree reaches 30-40%, and the thickness of the film is 0.04-0.1 mm; the alginate composite film layer 2 is made of sodium alginate, sodium polyacrylate , Shark collagen, pig skin collagen, chitosan quaternary ammonium salt, basic fibroblast growth factor (bFGF) several materials to form a fibrous membrane, the thickness of the membrane is 1 to 5 mm; the fibrous membrane is composed of fibers The filaments are superimposed and arranged. The fiber filaments have a core 4 and shell 3 structure, wherein the shell layer is composed of sodium alginate, sodium polyacrylate, shark collagen, and pig skin collagen materials; the core layer is composed of chitosan quaternary ammonium salt and growth Composed of factor materials, the surface of the fiber membrane is coated with a material layer containing calcium chloride and zinc chloride, and a material layer of processed Chinese medicine extracts of Bletilla striata, red peony root, blood jellyfish, common soft-shelled turtle, and comfrey.
一种治疗褥疮的海藻酸盐医用敷料的制备方法，包括如下步骤：A preparation method for an alginate medical dressing for treating decubitus, comprising the steps of:
A、取粉碎细度为20目的鲨鱼皮与鲨鱼软骨的含量比例为6.7:3.4的混合物干品，加入1:15质量的0.1N/L NaOH溶液，8℃温度下浸泡5小时，取出沥干；加入1:10的石油醚，8℃温度下浸泡12小时，用蒸馏水洗涤后沥干；再加1:10的2.5％的乙酸溶液，在8℃，搅拌速度300rpm的条件下搅拌48小时，40000转/min的条件下离心；取上清液加入1mol/L硫酸钠，经过沉淀、过滤、蒸馏水洗涤，再加1:10的2.5％的乙酸溶液溶解，采用北京陶氏超滤膜公司供应的截留分子量为100kDa的超滤膜超滤，滤液冷冻干燥，获得鲨鱼皮和软骨混合胶原蛋白，再取2％乙酸溶液溶解配成含混合胶原蛋白浓度为0.3％的溶液；A. Take the dry mixture of shark skin and shark cartilage with a crushing fineness of 20 mesh and a content ratio of 6.7:3.4, add 0.1N/L NaOH solution with a mass of 1:15, soak at 8°C for 5 hours, take out and drain Add 1:10 petroleum ether, soak at 8°C for 12 hours, wash with distilled water and drain; add 1:10 of 2.5% acetic acid solution, stir for 48 hours at 8°C, stirring speed 300rpm, Centrifuge under the condition of 40000 rev/min; take the supernatant and add 1mol/L sodium sulfate, after precipitation, filtration, distilled water washing, add 2.5% acetic acid solution of 1:10 to dissolve, and use Beijing Dow Ultrafiltration Membrane Company to supply Ultrafiltration with an ultrafiltration membrane with a molecular weight cut-off of 100kDa, the filtrate was freeze-dried to obtain mixed collagen from shark skin and cartilage, and then dissolved in 2% acetic acid solution to form a solution containing mixed collagen with a concentration of 0.3%;
B、取A步骤制备的溶液，在搅拌速度300rpm的条件下，加入海藻酸钠0.4％；加入聚丙烯酸钠，海藻酸钠与聚丙烯酸钠的重量比为1:0.2；加入猪皮胶原蛋白，海藻酸钠与猪皮胶原的重量比为1:0.05，搅拌20分钟；B. Take the solution prepared in step A, and add 0.4% sodium alginate at a stirring speed of 300rpm; add sodium polyacrylate, the weight ratio of sodium alginate to sodium polyacrylate is 1:0.2; add pigskin collagen, The weight ratio of sodium alginate and pigskin collagen is 1:0.05, stirring for 20 minutes;
C、以蒸馏水为溶剂，取碱性成纤维细胞生长因子(bFGF)，在搅拌速度300rpm的条件下，配制壳聚糖季铵盐和生长因子复合溶液，溶液中壳聚糖季铵盐含量为0.3％，bFGF生长因子含量为0.001％，搅拌10分钟；C, take distilled water as solvent, get basic fibroblast growth factor (bFGF), under the condition of stirring speed 300rpm, prepare chitosan quaternary ammonium salt and growth factor compound solution, chitosan quaternary ammonium salt content in the solution is 0.3%, bFGF growth factor content is 0.001%, stirring for 10 minutes;
D、以步骤B中所得到的海藻酸盐复合溶液作为纺丝的外层溶液，以步骤C中所得到的含壳聚糖季铵盐和生长因子复合溶液作为纺丝的内层溶液，进行同轴静电纺丝，在电压为30kV、固定阳极与阴极之间的距离为18cm，温度为28～30℃的条件下，进行同轴静电纺丝，在接收板上得到淡黄色、带有核壳结构的纤维丝并由纤维丝构成的海藻酸盐纤维膜；D, with the alginate composite solution obtained in step B as the outer layer solution of spinning, with the chitosan quaternary ammonium salt and growth factor composite solution obtained in step C as the inner layer solution of spinning, carry out Coaxial electrospinning, at a voltage of 30kV, a fixed distance between the anode and the cathode of 18cm, and a temperature of 28-30°C, the coaxial electrospinning is carried out, and a light yellow, with nuclei is obtained on the receiving plate. Fibrous filaments of the shell structure and an alginate fiber membrane composed of filaments;
E、以蒸馏水为溶剂，采用氯化钙和氯化锌，配制含3％氯化钙与0.5％氯化锌的氯化物混合液，将D步骤所得的纳米纤维膜浸入混合液中，然后取出干燥。浸入放置时间为20分钟，在35℃的热空气干燥，干燥时间为2小时；E. Using distilled water as a solvent, calcium chloride and zinc chloride are used to prepare a chloride mixture containing 3% calcium chloride and 0.5% zinc chloride, and the nanofiber membrane obtained in step D is immersed in the mixture, and then taken out dry. The soaking time is 20 minutes, and the drying time is 2 hours in hot air at 35°C;
F、取白芨、赤芍、血竭、土木鳖、紫草中药材各10克，加入120克水，浸泡20分钟后，煮沸25分钟，倒出液体，药渣再加水100克，再次煮沸20分钟，合并两次液体，加水定容200毫升，成为复合中药水煮液；取E步骤制得的交联海藻酸盐复合物浸入复合中药水煮液，然后取出干燥，浸入中药水煮液放置时间为2分钟，35℃热空气干燥，干燥时间为2小时；F. Take 10 grams each of Bletilla striata, Radix Paeoniae Rubra, Radix Dermatosa, Turtle, and Comfrey, add 120 grams of water, soak for 20 minutes, boil for 25 minutes, pour out the liquid, add 100 grams of water to the dregs, and boil again for 20 minutes. Minutes, combine the two liquids, add water to make up 200 ml to become a compound Chinese medicine boiled liquid; take the cross-linked alginate compound prepared in step E and immerse in the compound Chinese medicine boiled liquid, then take it out and dry it, immerse it in the traditional Chinese medicine boiled liquid and place it The time is 2 minutes, 35 ℃ hot air drying, the drying time is 2 hours;
G、取环氧化程度为32％的环氧化天然橡胶，溶解在四氢呋喃中，配制成1％溶液，然后通过流延法涂布在洁净不粘纸上，经过68℃的热空气干燥，干燥时间为2小时，获得的厚度为0.04毫米的环氧化天然橡胶薄膜；G, take the epoxidized natural rubber whose epoxidation degree is 32%, dissolve it in tetrahydrofuran, be mixed with 1% solution, then be coated on the clean non-stick paper by casting method, through the hot air drying of 68 ℃, The drying time was 2 hours, and the obtained thickness was an epoxidized natural rubber film of 0.04 mm;
H、复合H. Composite
将步骤F获得的复合物与步骤G获得的环氧化天然橡胶薄膜复合，即得到所述的治疗褥疮的海藻酸盐敷料。Composite the compound obtained in step F with the epoxidized natural rubber film obtained in step G to obtain the alginate dressing for treating decubitus.
实施例2Example 2
一种治疗褥疮的海藻酸盐医用敷料的制备方法，包括如下步骤：A preparation method for an alginate medical dressing for treating decubitus, comprising the steps of:
A、取粉碎细度为50目的鲨鱼皮与鲨鱼软骨的含量比例为6.4:3.6的混合物干品，加入1:15质量的0.1N/L NaOH溶液，8℃温度下浸泡5小时，取出沥干；加入1:10的石油醚，8℃温度下浸泡12小时，用蒸馏水洗涤后沥干；再加1:10的3.5％的乙酸溶液，在8℃，搅拌速度500rpm的条件下搅拌48小时，40000转/min的条件下离心；取上清液加入1mol/L硫酸钠，经过沉淀、过滤、蒸馏水洗涤，再加1:10的3.5％的乙酸溶液溶解，采用广州超禹膜分离技术有限公司供应的截留分子量为100kDa的超滤膜超滤，滤液冷冻干燥，获得鲨鱼皮和软骨混合胶原蛋白，再取2％乙酸溶液溶解配成含混合胶原蛋白浓度为0.3％的溶液。A. Take the dry mixture of shark skin and shark cartilage with a crushing fineness of 50 mesh and a content ratio of 6.4:3.6, add 0.1N/L NaOH solution with a mass of 1:15, soak at 8°C for 5 hours, take out and drain Add 1:10 petroleum ether, soak at 8°C for 12 hours, wash with distilled water and drain; add 1:10 of 3.5% acetic acid solution, stir for 48 hours at 8°C, stirring speed 500rpm, Centrifuge under the condition of 40000 rev/min; take the supernatant and add 1mol/L sodium sulfate, after precipitation, filtration, distilled water washing, add 1:10 3.5% acetic acid solution to dissolve, adopt Guangzhou Chaoyu Membrane Separation Technology Co., Ltd. The supplied ultrafiltration membrane with a molecular weight cut-off of 100kDa is ultrafiltered, and the filtrate is freeze-dried to obtain mixed collagen of shark skin and cartilage, and then dissolved in 2% acetic acid solution to form a solution containing mixed collagen with a concentration of 0.3%.
B、取A步骤制备的溶液，在搅拌速度500rpm的条件下，加入海藻酸钠0.7％；加入聚丙烯酸钠，海藻酸钠与聚丙烯酸钠的重量比为1:0.4；加入猪皮胶原蛋白，海藻酸钠与猪皮胶原的重量比为1:0.08，搅拌20分钟；B. Take the solution prepared in step A, and add 0.7% sodium alginate at a stirring speed of 500rpm; add sodium polyacrylate, the weight ratio of sodium alginate to sodium polyacrylate is 1:0.4; add pigskin collagen, The weight ratio of sodium alginate to pigskin collagen is 1:0.08, stirring for 20 minutes;
C、以蒸馏水为溶剂，取bFGF生长因子，在搅拌速度500rpm的条件下，配制壳聚糖季铵盐和生长因子复合溶液，溶液中壳聚糖季铵盐含量为0.5％，bFGF生长因子含量为0.001％，搅拌10分钟；C, take distilled water as solvent, get bFGF growth factor, under the condition of stirring speed 500rpm, prepare chitosan quaternary ammonium salt and growth factor compound solution, chitosan quaternary ammonium salt content is 0.5% in the solution, bFGF growth factor content 0.001%, stirring for 10 minutes;
D、以步骤B中所得到的海藻酸盐复合溶液作为纺丝的外层溶液，以步骤C中所得到的含壳聚糖季铵盐和生长因子复合溶液作为纺丝的内层溶液，进行同轴静电纺丝，在电压为30kV、固定阳极与阴极之间的距离为18cm，温度为28～30℃的条件下，进行同轴静电纺丝，在接收板上得到淡黄色、带有核壳结构的纤维丝并由纤维丝构成的海藻酸盐纤维膜；D, with the alginate composite solution obtained in step B as the outer layer solution of spinning, with the chitosan quaternary ammonium salt and growth factor composite solution obtained in step C as the inner layer solution of spinning, carry out Coaxial electrospinning, at a voltage of 30kV, a fixed distance between the anode and the cathode of 18cm, and a temperature of 28-30°C, the coaxial electrospinning is carried out, and a light yellow, with nuclei is obtained on the receiving plate. Fibrous filaments of the shell structure and an alginate fiber membrane composed of filaments;
E、以蒸馏水为溶剂，采用氯化钙和氯化锌，配制含3％氯化钙与0.5％氯化锌的氯化物混合液，将D步骤所得的纳米纤维膜浸入混合液中，然后，取出干燥，浸入放置时间为30分钟，40℃的热空气干燥，干燥时间为1小时；E, using distilled water as a solvent, adopting calcium chloride and zinc chloride, preparing a chloride mixed solution containing 3% calcium chloride and 0.5% zinc chloride, immersing the nanofiber membrane obtained in step D in the mixed solution, and then, Take out and dry, immerse and place for 30 minutes, dry with hot air at 40°C, and dry for 1 hour;
F、取白芨、赤芍、血竭、土木鳖、紫草中药材各10克，加入120克水，浸泡20分钟后，煮沸25分钟，倒出液体，药渣再加水100克，再次煮沸20分钟，合并两次液体，加水定容200毫升，成为复合中药水煮液；取E步骤制得的交联海藻酸盐复合物浸入复合中药水煮液，然后取出干燥，浸入中药水煮液放置时间为2分钟，热风条件为温度40℃的热空气，干燥时间为1小时；F. Take 10 grams each of Bletilla striata, Radix Paeoniae Rubra, Radix Dermatosa, Turtle, and Comfrey, add 120 grams of water, soak for 20 minutes, boil for 25 minutes, pour out the liquid, add 100 grams of water to the dregs, and boil again for 20 minutes. Minutes, combine the two liquids, add water to make up 200 ml to become a compound Chinese medicine boiled liquid; take the cross-linked alginate compound prepared in step E and immerse in the compound Chinese medicine boiled liquid, then take it out and dry it, immerse it in the traditional Chinese medicine boiled liquid and place it The drying time is 2 minutes, the hot air condition is hot air at a temperature of 40°C, and the drying time is 1 hour;
G、取环氧化程度为35％的环氧化天然橡胶，溶解在四氢呋喃中，配制成1％溶液，然后通过流延法涂布在洁净不粘纸上，70℃的热空气干燥，干燥时间为1小时，获得的厚度为0.1毫米的环氧化天然橡胶薄膜。G. Take epoxidized natural rubber with an epoxidation degree of 35%, dissolve it in tetrahydrofuran, prepare a 1% solution, and then apply it on a clean non-stick paper by casting method, dry it with hot air at 70°C, and dry it. The time is 1 hour, and an epoxidized natural rubber film with a thickness of 0.1 mm is obtained.
H、复合H. Composite
将步骤F获得的复合物与步骤G获得的环氧化天然橡胶薄膜复合，即得到所述的治疗褥疮的海藻酸盐敷料。Composite the compound obtained in step F with the epoxidized natural rubber film obtained in step G to obtain the alginate dressing for treating decubitus.
实施例3Example 3
一种治疗褥疮的海藻酸盐医用敷料的制备方法，包括如下步骤：A preparation method for an alginate medical dressing for treating decubitus, comprising the steps of:
A、取粉碎细度为35目的鲨鱼皮与鲨鱼软骨的含量比例为6:4的混合物干品，加入1:15质量的0.1N/L NaOH溶液，8℃温度下浸泡5小时，取出沥干；加入1:10的石油醚，8℃温度下浸泡12小时，用蒸馏水洗涤后沥干；再加1:10的3.0％的乙酸溶液，在8℃，搅拌速度400rpm的条件下搅拌48小时，40000转/min的条件下离心；取上清液加入1mol/L硫酸钠，经过沉淀、过滤、蒸馏水洗涤，再加1:10的3.0％的乙酸溶液溶解，采用广州超禹膜分离技术有限公司供应的截留分子量为100kDa的超滤膜超滤，滤液冷冻干燥，获得鲨鱼皮和软骨混合胶原蛋白，再取2％乙酸溶液溶解配成含混合胶原蛋白浓度为0.3％的溶液；A. Take the dry mixture of shark skin and shark cartilage with a crushing fineness of 35 mesh and a content ratio of 6:4, add 0.1N/L NaOH solution with a mass of 1:15, soak at 8°C for 5 hours, take out and drain Add 1:10 petroleum ether, soak at 8°C for 12 hours, wash with distilled water and drain; add 1:10 of 3.0% acetic acid solution, stir for 48 hours at 8°C, stirring speed 400rpm, Centrifuge under the condition of 40000 rev/min; take the supernatant and add 1mol/L sodium sulfate, after precipitation, filtration, distilled water washing, add 1:10 3.0% acetic acid solution to dissolve, adopt Guangzhou Chaoyu Membrane Separation Technology Co., Ltd. The supplied ultrafiltration membrane with a molecular weight cut-off of 100kDa is ultrafiltered, and the filtrate is freeze-dried to obtain mixed collagen from shark skin and cartilage, and then dissolved in 2% acetic acid solution to form a solution containing mixed collagen with a concentration of 0.3%;
B、取A步骤制备的溶液，在搅拌速度400rpm的条件下，加入海藻酸钠0.8％；加入聚丙烯酸钠，海藻酸钠与聚丙烯酸钠的重量比为1:0.3；加入猪皮胶原蛋白，海藻酸钠与猪皮胶原的重量比为1:0.06，搅拌20分钟；B. Take the solution prepared in step A, and add 0.8% sodium alginate at a stirring speed of 400rpm; add sodium polyacrylate, the weight ratio of sodium alginate to sodium polyacrylate is 1:0.3; add pigskin collagen, The weight ratio of sodium alginate to pigskin collagen is 1:0.06, stirring for 20 minutes;
C、以蒸馏水为溶剂，取bFGF生长因子，在搅拌速度400rpm的条件下，配制壳聚糖季铵盐和生长因子复合溶液，溶液中壳聚糖季铵盐含量为0.4％，bFGF生长因子含量为0.001％，搅拌10分钟；C, take distilled water as solvent, get bFGF growth factor, under the condition of stirring speed 400rpm, prepare chitosan quaternary ammonium salt and growth factor compound solution, chitosan quaternary ammonium salt content is 0.4% in the solution, bFGF growth factor content 0.001%, stirring for 10 minutes;
D、以步骤B中所得到的海藻酸盐复合溶液作为纺丝的外层溶液，以步骤C中所得到的含壳聚糖季铵盐和生长因子复合溶液作为纺丝的内层溶液，进行同轴静电纺丝，在电压为30kV、固定阳极与阴极之间的距离为18cm，温度为28～30℃的条件下，进行同轴静电纺丝，在接收板上得到淡黄色、带有核壳结构的纤维丝并由纤维丝构成的海藻酸盐纤维膜；D, with the alginate composite solution obtained in step B as the outer layer solution of spinning, with the chitosan quaternary ammonium salt and growth factor composite solution obtained in step C as the inner layer solution of spinning, carry out Coaxial electrospinning, at a voltage of 30kV, a fixed distance between the anode and the cathode of 18cm, and a temperature of 28-30°C, the coaxial electrospinning is carried out, and a light yellow, with nuclei is obtained on the receiving plate. Fibrous filaments of the shell structure and an alginate fiber membrane composed of filaments;
E、以蒸馏水为溶剂，采用氯化钙和氯化锌，配制含3％氯化钙与0.5％氯化锌的氯化物混合液，将D步骤所得的纳米纤维膜浸入混合液中，然后，取出干燥，浸入放置时间为25分钟，40℃的热空气干燥，干燥时间为1.5小时；E, using distilled water as a solvent, adopting calcium chloride and zinc chloride, preparing a chloride mixed solution containing 3% calcium chloride and 0.5% zinc chloride, immersing the nanofiber membrane obtained in step D in the mixed solution, and then, Take out and dry, immerse and place for 25 minutes, dry with hot air at 40°C, and dry for 1.5 hours;
F、取白芨、赤芍、血竭、土木鳖、紫草中药材各10克，加入120克水，浸泡20分钟后，煮沸25分钟，倒出液体，药渣再加水100克，再次煮沸20分钟，合并两次液体，加水定容200毫升，成为复合中药水煮液；取E步骤制得的交联海藻酸盐复合物浸入复合中药水煮液，然后取出干燥，浸入中药水煮液放置时间为2分钟，热风条件为温度37℃的热空气，干燥时间为1.5小时；F. Take 10 grams each of Bletilla striata, Radix Paeoniae Rubra, Radix Dermatosa, Turtle, and Comfrey, add 120 grams of water, soak for 20 minutes, boil for 25 minutes, pour out the liquid, add 100 grams of water to the dregs, and boil again for 20 minutes. Minutes, combine the two liquids, add water to make up 200 ml to become a compound Chinese medicine boiled liquid; take the cross-linked alginate compound prepared in step E and immerse in the compound Chinese medicine boiled liquid, then take it out and dry it, immerse it in the traditional Chinese medicine boiled liquid and place it The drying time is 2 minutes, the hot air condition is hot air at a temperature of 37°C, and the drying time is 1.5 hours;
G、取环氧化程度为40％的环氧化天然橡胶，溶解在四氢呋喃中，配制成1％溶液，然后通过流延法涂布在洁净不粘纸上，69℃的热空气干燥，干燥时间为1小时，获得的厚度为0.08毫米的环氧化天然橡胶薄膜；G. Take epoxidized natural rubber with an epoxidation degree of 40%, dissolve it in tetrahydrofuran, prepare a 1% solution, and then apply it on a clean non-stick paper by casting method, dry it with hot air at 69°C, and dry it. The time is 1 hour, and the obtained thickness is an epoxidized natural rubber film of 0.08 mm;
H、复合H. Composite
将步骤F获得的复合物与步骤G获得的环氧化天然橡胶薄膜复合，即得到所述的治疗褥疮的海藻酸盐敷料。Composite the compound obtained in step F with the epoxidized natural rubber film obtained in step G to obtain the alginate dressing for treating decubitus.
实施例4Example 4
一种治疗褥疮的海藻酸盐医用敷料的制备方法，包括如下步骤：A preparation method for an alginate medical dressing for treating decubitus, comprising the steps of:
A、取粉碎细度为40目的鲨鱼皮与鲨鱼软骨的含量比例为7:3的混合物干品，加入1:15质量的0.1N/L NaOH溶液，8℃温度下浸泡5小时，取出沥干；加入1:10的石油醚，8℃温度下浸泡12小时，用蒸馏水洗涤后沥干；再加1:10的2.8％的乙酸溶液，在8℃，搅拌速度3500rpm的条件下搅拌48小时，40000转/min的条件下离心；取上清液加入1mol/L硫酸钠，经过沉淀、过滤、蒸馏水洗涤，再加1:10的2.8％的乙酸溶液溶解，采用广州超禹膜分离技术有限公司供应的截留分子量为100kDa的超滤膜超滤，滤液冷冻干燥，获得鲨鱼皮和软骨混合胶原蛋白，再取2％乙酸溶液溶解配成含混合胶原蛋白浓度为0.3％的溶液；A. Take the dry mixture of shark skin and shark cartilage with a crushing fineness of 40 mesh and a content ratio of 7:3, add 0.1N/L NaOH solution with a mass of 1:15, soak at 8°C for 5 hours, take out and drain Add 1:10 petroleum ether, soak at 8°C for 12 hours, wash with distilled water and drain; add 1:10 of 2.8% acetic acid solution, stir for 48 hours at 8°C, stirring speed 3500rpm, Centrifuge under the condition of 40000 rev/min; take the supernatant and add 1mol/L sodium sulfate, after precipitation, filtration, distilled water washing, add 2.8% acetic acid solution of 1:10 to dissolve, adopt Guangzhou Chaoyu Membrane Separation Technology Co., Ltd. The supplied ultrafiltration membrane with a molecular weight cut-off of 100kDa is ultrafiltered, and the filtrate is freeze-dried to obtain mixed collagen from shark skin and cartilage, and then dissolved in 2% acetic acid solution to form a solution containing mixed collagen with a concentration of 0.3%;
B、取A步骤制备的溶液，在搅拌速度350rpm的条件下，加入海藻酸钠0.6％；加入聚丙烯酸钠，海藻酸钠与聚丙烯酸钠的重量比为1:0.25；加入猪皮胶原蛋白，海藻酸钠与猪皮胶原的重量比为1:0.07，搅拌20分钟；B. Take the solution prepared in step A, and add 0.6% sodium alginate at a stirring speed of 350rpm; add sodium polyacrylate, the weight ratio of sodium alginate to sodium polyacrylate is 1:0.25; add pigskin collagen, The weight ratio of sodium alginate to pigskin collagen is 1:0.07, stirring for 20 minutes;
C、以蒸馏水为溶剂，取bFGF生长因子，在搅拌速度350rpm的条件下，配制壳聚糖季铵盐和生长因子复合溶液，溶液中壳聚糖季铵盐含量为0.35％，bFGF生长因子含量为0.001％，搅拌10分钟；C, take distilled water as solvent, get bFGF growth factor, under the condition of stirring speed 350rpm, prepare chitosan quaternary ammonium salt and growth factor composite solution, chitosan quaternary ammonium salt content is 0.35% in the solution, bFGF growth factor content 0.001%, stirring for 10 minutes;
D、以步骤B中所得到的海藻酸盐复合溶液作为纺丝的外层溶液，以步骤C中所得到的含壳聚糖季铵盐和生长因子复合溶液作为纺丝的内层溶液，进行同轴静电纺丝，在电压为30kV、固定阳极与阴极之间的距离为18cm，温度为28～30℃的条件下，进行同轴静电纺丝，在接收板上得到淡黄色、带有核壳结构的纤维丝并由纤维丝构成的海藻酸盐纤维膜；D, with the alginate composite solution obtained in step B as the outer layer solution of spinning, with the chitosan quaternary ammonium salt and growth factor composite solution obtained in step C as the inner layer solution of spinning, carry out Coaxial electrospinning, at a voltage of 30kV, a fixed distance between the anode and the cathode of 18cm, and a temperature of 28-30°C, the coaxial electrospinning is carried out, and a light yellow, with nuclei is obtained on the receiving plate. Fibrous filaments of the shell structure and an alginate fiber membrane composed of filaments;
E、以蒸馏水为溶剂，采用氯化钙和氯化锌，配制含3％氯化钙与0.5％氯化锌的氯化物混合液，将D步骤所得的纳米纤维膜浸入混合液中，然后，取出干燥，浸入放置时间为28分钟，36℃的热空气干燥，干燥时间为1.2小时；E, using distilled water as a solvent, adopting calcium chloride and zinc chloride, preparing a chloride mixed solution containing 3% calcium chloride and 0.5% zinc chloride, immersing the nanofiber membrane obtained in step D in the mixed solution, and then, Take out and dry, immerse and place for 28 minutes, dry with hot air at 36°C, and dry for 1.2 hours;
F、取白芨、赤芍、血竭、土木鳖、紫草中药材各10克，加入120克水，浸泡20分钟后，煮沸25分钟，倒出液体，药渣再加水100克，再次煮沸20分钟，合并两次液体，加水定容200毫升，成为复合中药水煮液；取E步骤制得的交联海藻酸盐复合物浸入复合中药水煮液，然后取出干燥，浸入中药水煮液放置时间为2分钟，热风条件为温度36℃的热空气，干燥时间为1.5小时；F. Take 10 grams each of Bletilla striata, Radix Paeoniae Rubra, Radix Dermatosa, Turtle, and Comfrey, add 120 grams of water, soak for 20 minutes, boil for 25 minutes, pour out the liquid, add 100 grams of water to the dregs, and boil again for 20 minutes. Minutes, combine the two liquids, add water to make up 200 ml to become a compound Chinese medicine boiled liquid; take the cross-linked alginate compound prepared in step E and immerse in the compound Chinese medicine boiled liquid, then take it out and dry it, immerse it in the traditional Chinese medicine boiled liquid and place it The drying time is 2 minutes, the hot air condition is hot air at a temperature of 36°C, and the drying time is 1.5 hours;
G、取环氧化程度为30％的环氧化天然橡胶，溶解在四氢呋喃中，配制成1％溶液，然后通过流延法涂布在洁净不粘纸上，68℃的热空气干燥，干燥时间为1小时，获得的厚度为0.06毫米的环氧化天然橡胶薄膜；G. Take epoxidized natural rubber with an epoxidation degree of 30%, dissolve it in tetrahydrofuran, prepare a 1% solution, and then apply it on a clean non-stick paper by casting method, dry it with hot air at 68°C, and dry it. The time is 1 hour, and the obtained thickness is an epoxidized natural rubber film of 0.06 mm;
H、复合H. Composite
将步骤F获得的复合物与步骤G获得的环氧化天然橡胶薄膜复合，即得到所述的治疗褥疮的海藻酸盐敷料。Composite the compound obtained in step F with the epoxidized natural rubber film obtained in step G to obtain the alginate dressing for treating decubitus.
实施例4Example 4
一种治疗褥疮的海藻酸盐医用敷料的制备方法，包括如下步骤：A preparation method for an alginate medical dressing for treating decubitus, comprising the steps of:
A、取粉碎细度为40目的鲨鱼皮与鲨鱼软骨的含量比例为7:3的混合物干品，加入1:15质量的0.1N/L NaOH溶液，8℃温度下浸泡5小时，取出沥干；加入1:10的石油醚，8℃温度下浸泡12小时，用蒸馏水洗涤后沥干；再加1:10的2.8％的乙酸溶液，在8℃，搅拌速度3500rpm的条件下搅拌48小时，40000转/min的条件下离心；取上清液加入1mol/L硫酸钠，经过沉淀、过滤、蒸馏水洗涤，再加1:10的2.8％的乙酸溶液溶解，采用广州超禹膜分离技术有限公司供应的截留分子量为100kDa的超滤膜超滤，滤液冷冻干燥，获得鲨鱼皮和软骨混合胶原蛋白，再取2％乙酸溶液溶解配成含混合胶原蛋白浓度为0.3％的溶液；A. Take the dry mixture of shark skin and shark cartilage with a crushing fineness of 40 mesh and a content ratio of 7:3, add 0.1N/L NaOH solution with a mass of 1:15, soak at 8°C for 5 hours, take out and drain Add 1:10 petroleum ether, soak at 8°C for 12 hours, wash with distilled water and drain; add 1:10 of 2.8% acetic acid solution, stir for 48 hours at 8°C, stirring speed 3500rpm, Centrifuge under the condition of 40000 rev/min; take the supernatant and add 1mol/L sodium sulfate, after precipitation, filtration, distilled water washing, add 2.8% acetic acid solution of 1:10 to dissolve, adopt Guangzhou Chaoyu Membrane Separation Technology Co., Ltd. The supplied ultrafiltration membrane with a molecular weight cut-off of 100kDa is ultrafiltered, and the filtrate is freeze-dried to obtain mixed collagen from shark skin and cartilage, and then dissolved in 2% acetic acid solution to form a solution containing mixed collagen with a concentration of 0.3%;
B、取A步骤制备的溶液，在搅拌速度350rpm的条件下，加入海藻酸钠0.6％；加入聚丙烯酸钠，海藻酸钠与聚丙烯酸钠的重量比为1:0.25；加入猪皮胶原蛋白，海藻酸钠与猪皮胶原的重量比为1:0.07，搅拌20分钟；B. Take the solution prepared in step A, and add 0.6% sodium alginate at a stirring speed of 350rpm; add sodium polyacrylate, the weight ratio of sodium alginate to sodium polyacrylate is 1:0.25; add pigskin collagen, The weight ratio of sodium alginate and pigskin collagen is 1:0.07, stirring for 20 minutes;
C、以蒸馏水为溶剂，取bFGF生长因子，在搅拌速度350rpm的条件下，配制壳聚糖季铵盐和生长因子复合溶液，溶液中壳聚糖季铵盐含量为0.35％，bFGF生长因子含量为0.001％，搅拌10分钟；C, take distilled water as solvent, get bFGF growth factor, under the condition of stirring speed 350rpm, prepare chitosan quaternary ammonium salt and growth factor composite solution, chitosan quaternary ammonium salt content is 0.35% in the solution, bFGF growth factor content 0.001%, stirring for 10 minutes;
D、以步骤B中所得到的海藻酸盐复合溶液作为纺丝的外层溶液，以步骤C中所得到的含壳聚糖季铵盐和生长因子复合溶液作为纺丝的内层溶液，进行同轴静电纺丝，在电压为30kV、固定阳极与阴极之间的距离为18cm，温度为28～30℃的条件下，进行同轴静电纺丝，在接收板上得到淡黄色、带有核壳结构的纤维丝并由纤维丝构成的海藻酸盐纤维膜；D, with the alginate composite solution obtained in step B as the outer layer solution of spinning, with the chitosan quaternary ammonium salt and growth factor composite solution obtained in step C as the inner layer solution of spinning, carry out Coaxial electrospinning, at a voltage of 30kV, a fixed distance between the anode and the cathode of 18cm, and a temperature of 28-30°C, the coaxial electrospinning is carried out, and a light yellow, with nuclei is obtained on the receiving plate. Fibrous filaments of the shell structure and an alginate fiber membrane composed of filaments;
E、以蒸馏水为溶剂，采用氯化钙和氯化锌，配制含3％氯化钙与0.5％氯化锌的氯化物混合液，将D步骤所得的纳米纤维膜浸入混合液中，然后，取出干燥，浸入放置时间为28分钟，36℃的热空气干燥，干燥时间为1.2小时；E, using distilled water as a solvent, adopting calcium chloride and zinc chloride, preparing a chloride mixed solution containing 3% calcium chloride and 0.5% zinc chloride, immersing the nanofiber membrane obtained in step D in the mixed solution, and then, Take out and dry, immerse and place for 28 minutes, dry with hot air at 36°C, and dry for 1.2 hours;
F、取白芨、赤芍、血竭、土木鳖、紫草中药材各10克，加入120克水，浸泡20分钟后，煮沸25分钟，倒出液体，药渣再加水100克，再次煮沸20分钟，合并两次液体，加水定容200毫升，成为复合中药水煮液；取E步骤制得的交联海藻酸盐复合物浸入复合中药水煮液，然后取出干燥，浸入中药水煮液放置时间为2分钟，热风条件为温度36℃的热空气，干燥时间为1.5小时；F. Take 10 grams each of Bletilla striata, Radix Paeoniae Rubra, Radix Dermatosa, Turtle, and Comfrey, add 120 grams of water, soak for 20 minutes, boil for 25 minutes, pour out the liquid, add 100 grams of water to the dregs, and boil again for 20 minutes. Minutes, combine the two liquids, add water to make up 200 ml to become a compound Chinese medicine boiled liquid; take the cross-linked alginate compound prepared in step E and immerse in the compound Chinese medicine boiled liquid, then take it out and dry it, immerse it in the traditional Chinese medicine boiled liquid and place it The drying time is 2 minutes, the hot air condition is hot air at a temperature of 36°C, and the drying time is 1.5 hours;
G、取环氧化程度为30％的环氧化天然橡胶，溶解在四氢呋喃中，配制成1％溶液，然后通过流延法涂布在洁净不粘纸上，68℃的热空气干燥，干燥时间为1小时，获得的厚度为0.06毫米的环氧化天然橡胶薄膜；G. Take epoxidized natural rubber with an epoxidation degree of 30%, dissolve it in tetrahydrofuran, prepare a 1% solution, and then apply it on a clean non-stick paper by casting method, dry it with hot air at 68°C, and dry it. The time is 1 hour, and the obtained thickness is an epoxidized natural rubber film of 0.06 mm;
H、复合H. Composite
将步骤F获得的复合物与步骤G获得的环氧化天然橡胶薄膜复合，即得到所述的治疗褥疮的海藻酸盐敷料。Composite the compound obtained in step F with the epoxidized natural rubber film obtained in step G to obtain the alginate dressing for treating decubitus.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510100226.3ACN104758977B (en) | 2014-10-11 | 2015-03-07 | A kind of alginate dressing for treating bedsore and preparation method thereof |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410534890 | 2014-10-11 | ||
| CN2014105348904 | 2014-10-11 | ||
| CN201510100226.3ACN104758977B (en) | 2014-10-11 | 2015-03-07 | A kind of alginate dressing for treating bedsore and preparation method thereof |
| Publication Number | Publication Date |
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| CN104758977Atrue CN104758977A (en) | 2015-07-08 |
| CN104758977B CN104758977B (en) | 2017-11-24 |
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| CN201510100226.3AExpired - Fee RelatedCN104758977B (en) | 2014-10-11 | 2015-03-07 | A kind of alginate dressing for treating bedsore and preparation method thereof |
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| CN106729939A (en)* | 2016-12-29 | 2017-05-31 | 河南亚都实业有限公司 | A kind of dressing for treating bedsore |
| CN107237005A (en)* | 2017-06-19 | 2017-10-10 | 山东大学 | A kind of alginic acid and chitosan bicomponent fibers and preparation method thereof |
| CN107485484A (en)* | 2017-09-01 | 2017-12-19 | 山东汉方生物科技有限公司 | Suitable for general sexual trauma, the wound of chronic trauma patch |
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| CN111330063A (en)* | 2020-01-21 | 2020-06-26 | 广东工业大学 | A kind of nanofiber membrane and preparation method thereof |
| CN115531594A (en)* | 2022-10-19 | 2022-12-30 | 南通大学 | Diabetic wound healing dressing and preparation method thereof |
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| EP0099758A2 (en)* | 1982-07-21 | 1984-02-01 | University of Strathclyde | Composite wound dressing |
| US20040153040A1 (en)* | 2003-02-05 | 2004-08-05 | Lucie Martineau | Multi-layer synthetic dressing with cooling characteristics |
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| CN107237005B (en)* | 2017-06-19 | 2020-06-09 | 山东大学 | A kind of alginic acid and chitosan bicomponent fiber and preparation method thereof |
| CN107237005A (en)* | 2017-06-19 | 2017-10-10 | 山东大学 | A kind of alginic acid and chitosan bicomponent fibers and preparation method thereof |
| CN107485484A (en)* | 2017-09-01 | 2017-12-19 | 山东汉方生物科技有限公司 | Suitable for general sexual trauma, the wound of chronic trauma patch |
| CN107693834A (en)* | 2017-09-22 | 2018-02-16 | 青岛明月生物医用材料有限公司 | A kind of alginate medical dressing for loading collagen and preparation method thereof |
| CN108114307A (en)* | 2018-02-07 | 2018-06-05 | 苏州元禾医疗器械有限公司 | The preparation method of the medical dressing of high-biocompatibility |
| CN108159474A (en)* | 2018-02-07 | 2018-06-15 | 苏州元禾医疗器械有限公司 | A kind of preparation method for the dressing for being suitable for burn |
| CN108187123A (en)* | 2018-02-07 | 2018-06-22 | 苏州元禾医疗器械有限公司 | A kind of absorbable hemostasia dressing |
| CN108210977A (en)* | 2018-02-07 | 2018-06-29 | 苏州元禾医疗器械有限公司 | The absorption styptic dressing of high imbibition ability |
| CN108714234A (en)* | 2018-06-05 | 2018-10-30 | 广西中医药大学 | Biodegradable graphene oxide composite cellulosic membrane and its preparation method and application |
| CN108714234B (en)* | 2018-06-05 | 2021-03-26 | 广西中医药大学 | Biodegradable graphene oxide composite fiber membrane and preparation method and application thereof |
| CN109908395A (en)* | 2018-08-17 | 2019-06-21 | 上海昊海生物科技股份有限公司 | A kind of preparation method of shark skin natural medical collagen sponge |
| CN109498830A (en)* | 2018-10-22 | 2019-03-22 | 江阴奔翔生物科技有限公司 | A kind of method of the sodium alginate-modified acellular dermal matrix of epoxy |
| CN109731057A (en)* | 2019-01-17 | 2019-05-10 | 北京化工大学 | A kind of fibrous membrane with sustainable release of Dracula and preparation method thereof |
| CN110353883A (en)* | 2019-07-10 | 2019-10-22 | 重庆市人民医院 | For treating the combine dressing layer of bedsore and the bedsore with combine dressing layer is pasted |
| CN110960722A (en)* | 2019-12-14 | 2020-04-07 | 广东泰宝医疗科技股份有限公司 | Antibacterial alginate bandage and preparation method thereof |
| CN111330063A (en)* | 2020-01-21 | 2020-06-26 | 广东工业大学 | A kind of nanofiber membrane and preparation method thereof |
| CN115531594A (en)* | 2022-10-19 | 2022-12-30 | 南通大学 | Diabetic wound healing dressing and preparation method thereof |
| CN115531594B (en)* | 2022-10-19 | 2023-07-04 | 南通大学 | A kind of diabetic wound healing dressing and preparation method thereof |
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