CN116077708A - A drug-loaded long-acting anti-infection antibacterial and disinfection liquid crystal film and its preparation method - Google Patents

Abstract

Translated fromChinese

本发明提供一种负载药物的长效防感染抗菌消毒液晶膜及其制备方法，所述负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。本发明的负载药物的长效防感染抗菌消毒液晶膜，适用于治疗皮肤、腔道、创伤、组织的创伤，防感染、抗菌药物的作用时间长，防感染、抗菌、消毒效果好。

The invention provides a drug-loaded long-acting anti-infection, anti-bacterial and disinfecting liquid crystal film and a preparation method thereof. The drug-loaded long-acting anti-infection, anti-bacterial and disinfecting liquid crystal film includes a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; The dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; the slow-release layer is loaded with the antibacterial drugs. The drug-loaded long-acting anti-infection, anti-bacterial and disinfecting liquid crystal film of the present invention is suitable for treating skin, cavities, wounds, and tissue wounds. The anti-infection and antibacterial drugs have long action time and good anti-infection, antibacterial, and disinfection effects.

Description

Translated fromChinese

一种负载药物的长效防感染抗菌消毒液晶膜及其制备方法A drug-loaded long-acting anti-infection antibacterial and disinfection liquid crystal film and its preparation method

技术领域technical field

本发明涉及医用材料领域，特别是指一种负载药物的长效防感染抗菌消毒液晶膜及其制备方法。The invention relates to the field of medical materials, in particular to a drug-loaded long-acting anti-infection antibacterial and disinfection liquid crystal film and a preparation method thereof.

背景技术Background technique

接触人体的无源医疗器械主要使用于皮肤表面、破损皮肤、腔道、创伤、组织。其中，皮肤是人体面积最大的、且具有特殊细致组织结构的人体重要器官，皮肤的功能是防止细菌、真菌侵蚀和细菌感染、分泌油脂、滋润保护人体、调节人体体温和排泄体液等。大面积皮肤损伤除了皮肤和组织受到破坏以外，还有常常引起整个身体一系列复杂的病理、生理变化，如新陈代谢加剧、水分和蛋白质过度散失、免疫系统失调等，伴随着感染面积扩大重度皮肤缺损严重威胁人们的健康和生命。尤其对于全皮层缺损伤口，人体自身需要较长时间去修复，急性和慢性难愈合伤口治疗一直是临床的重要问题。腔道主要包括口腔、鼻腔、食道、外耳道、直肠、阴道、尿道等人体自然腔道和永久性人造开口，是人体面对外部环境的通道口。腔道较为脆弱，容易被病毒、细菌侵入，容易出现溃疡、炎症、肿痛等症状。创伤是指各种致伤因素作用于人体所造成的组织结构完整性破坏或者功能障碍。创伤的愈合是一个复杂的生物学过程，包括止血、炎症、细胞增生、瘢痕形成和表皮及其他组织再生。组织是指人体体内组织，包括骨、牙髓或者牙本质，不包括血液循环系统和中枢神经系统。组织创伤后的愈合通常是身体组织受到外力作用后，皮肤等身体组织出现受伤后的修复过程，而伤口的愈合一般可分为凝血期、组织炎症期、组织修复期、组织重塑期。Passive medical devices that come into contact with the human body are mainly used on skin surfaces, damaged skin, cavities, wounds, and tissues. Among them, the skin is an important organ with the largest area in the human body and has a special and delicate tissue structure. The functions of the skin are to prevent bacterial and fungal erosion and bacterial infection, secrete oil, moisturize and protect the human body, regulate body temperature and excrete body fluids. In addition to the destruction of the skin and tissues, large-scale skin damage often causes a series of complex pathological and physiological changes in the whole body, such as increased metabolism, excessive loss of water and protein, immune system disorders, etc., accompanied by the expansion of the infected area and severe skin defects Serious threat to people's health and life. Especially for full-thickness wounds, the human body takes a long time to repair, and the treatment of acute and chronic refractory wounds has always been an important clinical issue. Cavities mainly include oral cavity, nasal cavity, esophagus, external auditory canal, rectum, vagina, urethra and other natural orifices of the human body and permanent artificial openings, which are the passageways for the human body to face the external environment. The cavity is relatively fragile, easily invaded by viruses and bacteria, and is prone to symptoms such as ulcers, inflammation, and swelling. Trauma refers to the destruction of tissue structure integrity or dysfunction caused by various injury factors acting on the human body. Wound healing is a complex biological process that includes hemostasis, inflammation, cell proliferation, scar formation, and regeneration of the epidermis and other tissues. Tissue refers to the tissues in the human body, including bone, dental pulp or dentin, excluding the blood circulation system and central nervous system. Healing after tissue trauma is usually a repair process after body tissues are subjected to external forces, and skin and other body tissues are injured. Wound healing can generally be divided into coagulation phase, tissue inflammation phase, tissue repair phase, and tissue remodeling phase.

目前，外用治疗皮肤、破损皮肤、腔道、创伤、组织的创伤防感染、抗菌药物，主要是软膏状、凝胶状、粉状、液体状药物，其主要存在以下缺陷：抗菌作用时间短，一般只能达到4-8小时；另外，当伤口渗液多时，使用例如软膏类药物很容易覆盖伤口，导致伤口的分泌物很难引流出来，反而有可能会令细菌在里面繁殖得更加严重，导致伤口的炎症加重。At present, the anti-infection and antibacterial drugs for external treatment of skin, damaged skin, cavities, wounds, and tissues are mainly ointment, gel, powder, and liquid drugs, which mainly have the following defects: the antibacterial action time is short, Generally, it can only last for 4-8 hours; in addition, when the wound exudates a lot, it is easy to cover the wound with ointment, which makes it difficult to drain the wound secretion, which may cause the bacteria to multiply inside. lead to increased inflammation of the wound.

发明内容Contents of the invention

本发明的目的在于提供一种负载药物的长效防感染抗菌消毒液晶膜及其制备方法，以解决现有技术中的外用治疗皮肤、破损皮肤、腔道、创伤、组织的创伤缺乏防感染药物、且目前抗菌药物的作用时间短，容易导致细菌繁殖、加重伤口炎症的技术问题。The purpose of the present invention is to provide a drug-loaded long-acting anti-infection antibacterial and disinfecting liquid crystal film and its preparation method to solve the lack of anti-infection drugs in the prior art for external treatment of skin, damaged skin, cavities, wounds, and tissue wounds , and the action time of current antibacterial drugs is short, which easily leads to the technical problems of bacterial reproduction and aggravating wound inflammation.

为解决上述技术问题，本发明的技术方案如下：In order to solve the problems of the technologies described above, the technical solution of the present invention is as follows:

一种负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。A drug-loaded long-acting anti-infection, antibacterial, and disinfecting liquid crystal film, including a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; the dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; the slow-release layer The layer is loaded with the antibacterial drug.

上述各层中，所述敷料层作为底层，与人体直接接触，可起到“打底”的作用。所述缓释层作为中层，其负载有所述抗菌药物，可缓慢释放抗菌药物，起到维持涂层持久性的作用，具有与敷料层良好的粘附能力。所述隔离层作为上层，可提供良好的耐磨性、耐洗性。Among the above layers, the dressing layer is used as the bottom layer, which is in direct contact with the human body and can play the role of "priming". The slow-release layer is used as the middle layer, which is loaded with the antibacterial drug, can slowly release the antibacterial drug, plays a role in maintaining the durability of the coating, and has good adhesion to the dressing layer. As the upper layer, the isolation layer can provide good abrasion resistance and washability.

优选地，所述抗菌药物为聚六亚甲基双胍盐酸盐、枸橼酸、甲基苯酚、苄索氯铵、茶多酚中的一种或多种。Preferably, the antibacterial drug is one or more of polyhexamethylene biguanide hydrochloride, citric acid, methylphenol, benzethonium chloride, and tea polyphenols.

优选地，所述敷料层还包括液晶成膜材料；Preferably, the dressing layer also includes a liquid crystal film-forming material;

所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。The liquid crystal film-forming material is one or more of polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester, and 2-methacryloyloxyethyl phosphorylcholine.

优选地，所述敷料层包括如下重量份的原料：Preferably, the dressing layer comprises the following raw materials in parts by weight:

抗菌药物    100份；100 copies of antibacterial drugs;

聚乳酸      300-500份；Polylactic acid 300-500 parts;

透明质酸    500-600份。Hyaluronic acid 500-600 parts.

优选地，所述缓释层包括聚乙烯亚胺；或者，Preferably, the sustained release layer comprises polyethyleneimine; or,

所述缓释层包括聚酰亚胺、发泡剂。The slow-release layer includes polyimide and foaming agent.

优选地，所述缓释层包括如下重量份的原料：Preferably, the slow-release layer includes the following raw materials in parts by weight:

优选地，所述缓释层包括如下重量份的原料：Preferably, the slow-release layer includes the following raw materials in parts by weight:

优选地，所述隔离层包括聚乙烯醇、多巴胺中的一种或多种。Preferably, the isolation layer includes one or more of polyvinyl alcohol and dopamine.

优选地，所述隔离层包括如下重量份的原料：Preferably, the isolation layer includes the following raw materials in parts by weight:

聚乙烯醇   100份；100 parts of polyvinyl alcohol;

多巴胺     10-30份。Dopamine 10-30 parts.

本发明还提供一种所述的负载药物的长效防感染抗菌消毒液晶膜的制备方法，其特征在于，包括如下步骤：The present invention also provides a preparation method of the drug-loaded long-acting anti-infection antibacterial and disinfecting liquid crystal film, which is characterized in that it comprises the following steps:

(1)取抗菌药物、液晶成膜材料，混合均匀，涂覆成膜，形成敷料层；(1) Take antibacterial drugs and liquid crystal film-forming materials, mix them evenly, and coat them to form a film to form a dressing layer;

(2)取缓释层的原料，混合均匀，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，形成缓释层；(2) Take the raw materials of the slow-release layer, mix them uniformly to form a first prefabricated solution, and coat the first prefabricated solution on the dressing layer in step (1) to form a film to form a sustained-release layer;

(3)取聚乙烯醇、多巴胺，混合均匀，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。(3) Take polyvinyl alcohol and dopamine, mix them uniformly to form a second preformed solution, and coat the second preformed solution on the slow-release layer in step (2) to form a film to form an isolation layer.

优选地，步骤(1)中，取抗菌药物、液晶成膜材料，在65-75℃下，搅拌20-30min，涂覆成膜，形成敷料层。Preferably, in step (1), take antibacterial drugs and liquid crystal film-forming materials, stir at 65-75° C. for 20-30 min, and coat to form a film to form a dressing layer.

优选地，步骤(2)中，取抗菌药物、聚乳酸、透明质酸、聚乙烯亚胺，在70-80℃下，搅拌20-30min，混合均匀，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，形成缓释层。Preferably, in step (2), take antibacterial drugs, polylactic acid, hyaluronic acid, and polyethyleneimine, stir at 70-80°C for 20-30min, and mix uniformly to form the first prefabricated solution, and mix the The first preformed solution is coated on the dressing layer in step (1) to form a film to form a slow-release layer.

优选地，步骤(2)中，取抗菌药物、聚乳酸、聚酰亚胺、透明质酸、聚酰亚胺、发泡剂，在20-30℃下，搅拌20-30min，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，并在55-65℃下，固化3-5h，形成缓释层。Preferably, in step (2), take antibacterial drugs, polylactic acid, polyimide, hyaluronic acid, polyimide, and foaming agent, and stir for 20-30 minutes at 20-30°C to form the first prefabricated liquid, and the first prefabricated liquid is coated on the dressing layer in step (1) to form a film, and cured at 55-65° C. for 3-5 hours to form a slow-release layer.

优选地，步骤(3)中，取聚乙烯醇、多巴胺，在70-80℃下，搅拌20-30min，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。Preferably, in step (3), polyvinyl alcohol and dopamine are taken and stirred at 70-80°C for 20-30 minutes to form a second preformed liquid, and the second preformed liquid is mixed with the prepared liquid in step (2). Coating and forming a film on the slow-release layer to form a barrier layer.

本发明的上述方案至少包括以下有益效果：Above-mentioned scheme of the present invention comprises following beneficial effect at least:

(1)本发明的负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。其中，所述敷料层为具有仿细胞膜结构的液晶体，能够覆盖伤口，起到吸附伤口渗液的作用，同时，所述敷料层中含有的抗菌药物起到防感染抗菌的作用，保障伤口无菌。所述缓释层负载有所述抗菌药物，能够向所述敷料层传递防感染、抗菌物质，起到长效防感染、抗菌的作用；所述隔离层与所述设于所述缓释层上，起到防水防摩擦的作用，在使用过程中，遇到摩擦可以保护所述负载药物的长效防感染抗菌消毒液晶膜不被破坏。(1) The drug-loaded long-acting anti-infection, antibacterial and disinfecting liquid crystal film of the present invention includes a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; the dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; The sustained-release layer is loaded with the antibacterial drug. Wherein, the dressing layer is a liquid crystal with an imitation cell membrane structure, which can cover the wound and play the role of absorbing wound exudate. bacteria. The slow-release layer is loaded with the antibacterial drug, which can deliver anti-infection and antibacterial substances to the dressing layer, and play a role of long-term anti-infection and antibacterial; the isolation layer and the On the surface, it plays the role of waterproof and anti-friction. During use, friction can protect the long-acting anti-infection, anti-bacterial and disinfection liquid crystal film loaded with drugs from being damaged.

(2)本发明的负载药物的长效防感染抗菌消毒液晶膜，所述抗菌药物为聚六亚甲基双胍盐酸盐、枸橼酸、甲基苯酚、苄索氯铵、茶多酚中的一种或多种。(2) The long-acting anti-infection antibacterial disinfection liquid crystal film loaded with drugs of the present invention, the antibacterial drugs are polyhexamethylene biguanide hydrochloride, citric acid, methylphenol, benzethonium chloride, tea polyphenols one or more of .

其中，聚六亚甲基双胍盐酸盐中的胍基活性高，具极强的呈正电性，由于各类细菌、病毒均呈负电性，因此聚六亚甲基胍盐可以与带负电的细菌病毒结合，吸附带负电的细菌和病毒，进而破坏细菌的细胞壁及脂质层，破坏病毒的刺突蛋白，从而使细菌、病毒无法分裂繁殖，丧失活性，即使细菌、病毒变异也不会影响其发挥灭活作用。聚六亚甲基双胍盐酸盐不产生抗药性，且杀菌广谱，可以杀灭金黄色葡萄球菌、沙门氏菌、弯曲杆菌、大肠杆菌、痢疾杆菌、白色念珠菌等多种细菌、致病真菌等。Among them, the guanidine group in polyhexamethylene biguanide hydrochloride has high activity and is extremely positively charged. Since all kinds of bacteria and viruses are negatively charged, polyhexamethylene guanidine salt can be combined with negatively charged Bacteria and viruses combine to adsorb negatively charged bacteria and viruses, and then destroy the cell wall and lipid layer of bacteria, and destroy the spike protein of viruses, so that bacteria and viruses cannot divide and reproduce, and lose their activity. Even if bacteria and viruses mutate, it will not affect It exerts an inactivating effect. Polyhexamethylene biguanide hydrochloride does not produce drug resistance, and has a broad spectrum of sterilization, which can kill Staphylococcus aureus, Salmonella, Campylobacter, Escherichia coli, Shigella, Candida albicans and other bacteria, pathogenic fungi, etc. .

枸橼酸即3-羧基-3-羟基戊二酸，可起到降低pH值的作用，使有害微生物的增殖及毒素的产生受到抑制，有明显的防霉作用。Citric acid, namely 3-carboxy-3-hydroxyglutaric acid, can lower the pH value, inhibit the proliferation of harmful microorganisms and the production of toxins, and have obvious anti-mold effects.

甲基苯酚具有较好的杀菌作用，可以协同聚六亚甲基双胍盐酸盐共同起到良好的杀菌效果。Cresol has a good bactericidal effect, and can cooperate with polyhexamethylene biguanide hydrochloride to achieve a good bactericidal effect.

苄索氯铵不仅可以起到杀菌作用，同时，其分子结构中同时具有正、负电荷基团，在不同pH值介质中较稳定，具有较好的表面活性。Benzethonium chloride can not only play a bactericidal role, but also has both positive and negative charge groups in its molecular structure, which is relatively stable in media with different pH values and has good surface activity.

茶多酚是茶叶中多羟基酚类化合物的复合物，由30种以上的酚类物质组成，其主体成分是儿茶素及其衍生物。茶多酚对普通变形杆菌、金黄色葡萄球菌、表皮葡萄球菌、变形链球菌、肉毒杆菌、乳酸杆菌、霍乱弧菌和口腔变链菌等许多致病菌具有不同程度的抑制和杀伤作用，同时还能有效地防止耐抗生素的葡萄球菌感染，对于溶血素也具有抑制活性。另外，茶多酚具有多个邻位酚醛基结构，具有将强的供氢功能，能够显著清楚体内的有害自由基，并形成稳定的自由基中间体，保护细胞成分不受损伤。Tea polyphenols are complexes of polyhydric phenolic compounds in tea leaves, consisting of more than 30 kinds of phenolic substances, the main components of which are catechins and their derivatives. Tea polyphenols have varying degrees of inhibitory and killing effects on many pathogenic bacteria such as Proteus vulgaris, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Botulinum, Lactobacillus, Vibrio cholerae and Streptococcus oral mutans. At the same time, it can effectively prevent antibiotic-resistant Staphylococcus infection and also has inhibitory activity on hemolysin. In addition, tea polyphenols have multiple ortho phenolic group structures, which have a strong hydrogen supply function, can significantly clear harmful free radicals in the body, and form stable free radical intermediates to protect cell components from damage.

(3)本发明的负载药物的长效防感染抗菌消毒液晶膜，所述敷料层还包括液晶成膜材料；所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。通过所述液晶成膜材料，可以得到呈液晶态的膜材料，实现良好的生物相容性，由此形成的敷料层能够具有良好的透气性，更亲肤，在将裸露的创面暂时性覆盖时，可提供有利于创面愈合、阻止细菌滋生、防止感染、促进组织修复的环境，具有良好的生物学性，可有效保障伤口无菌，提高愈合速度，尽快地修复皮肤缺损创面，恢复其生理能。(3) The long-acting anti-infection antibacterial disinfection liquid crystal film loaded with drugs of the present invention, the dressing layer also includes a liquid crystal film-forming material; the liquid crystal film-forming material is polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester , one or more of 2-methacryloyloxyethyl phosphorylcholine. Through the liquid crystal film-forming material, a film material in a liquid crystal state can be obtained to achieve good biocompatibility. The dressing layer thus formed can have good air permeability and is more skin-friendly, and can temporarily cover the exposed wound surface. When used, it can provide an environment conducive to wound healing, prevent bacterial growth, prevent infection, and promote tissue repair. It has good biological properties, can effectively guarantee wound sterility, improve healing speed, repair skin defect wound as soon as possible, and restore its physiology. able.

(4)本发明的负载药物的长效防感染抗菌消毒液晶膜，所述缓释层还包括聚乙烯亚胺。聚乙烯亚胺由于具有极性基团氨基和疏水基乙烯基结构，能够与所述敷料层的成分进行混合，并包覆所述敷料层形成微胶囊，进而减少所述敷料层中所述抗菌药物的挥发，在遇到病毒细菌时，呈正电性的所述缓释层，与各类呈负电性细菌、病毒结合，吸附带负电的细菌和病毒，仿细胞膜结构的微胶囊释放抗菌药物，进而破坏细菌的细胞壁及脂质层，破坏病毒的刺突蛋白，使细菌、病毒无法分裂繁殖，阻止病原微生物呼吸，使其丧失活性。同时，聚乙烯亚胺也具有较好的透气性。(4) In the drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film of the present invention, the slow-release layer further includes polyethyleneimine. Since polyethyleneimine has a polar group amino group and a hydrophobic vinyl structure, it can be mixed with the ingredients of the dressing layer and coated with the dressing layer to form microcapsules, thereby reducing the antibacterial effect in the dressing layer. When the drug volatilizes, when encountering virus bacteria, the positively charged slow-release layer combines with various negatively charged bacteria and viruses to absorb negatively charged bacteria and viruses, and the microcapsules imitating the cell membrane structure release antibacterial drugs, Then destroy the cell wall and lipid layer of bacteria, destroy the spike protein of virus, make bacteria and virus unable to divide and reproduce, prevent pathogenic microorganisms from breathing, and make them lose their activity. At the same time, polyethyleneimine also has good air permeability.

所述缓释层还可以包括聚酰亚胺、发泡剂。所述聚酰亚胺作为所述缓释层的基材，通过与所述敷料层的成分进行混合，在发泡剂的作用下形成能够容纳所述敷料层的成分的多孔材料，进而减少所述敷料层中所述抗菌药物的挥发，使所述抗菌药物缓慢释放，进而实现长效的防感染、抗菌效果。The sustained-release layer may also include polyimide and a foaming agent. The polyimide, as the base material of the slow-release layer, is mixed with the ingredients of the dressing layer to form a porous material capable of accommodating the ingredients of the dressing layer under the action of a foaming agent, thereby reducing the The volatilization of the antibacterial drug in the dressing layer makes the antibacterial drug slowly released, thereby realizing long-term anti-infection and antibacterial effects.

(5)本发明的负载药物的长效防感染抗菌消毒液晶膜，所述隔离层包括聚乙烯醇、多巴胺中的一种或多种。所述聚乙烯醇的成膜性良好，且成膜的机械性能优良。所述多巴胺在弱碱性水溶液中能够发生氧化-自聚，并形成聚多巴胺。聚多巴胺具有较强的吸附性能，能够使所述隔离层与所述缓释层具较强的结合力，且在水环境中表现出较强的稳定性。所述聚乙烯醇与所述多巴胺混合后，得到的所述隔离层不仅具有良好的机械强度，还与所述缓释层具有较强的结合力。(5) In the drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film of the present invention, the isolation layer includes one or more of polyvinyl alcohol and dopamine. The polyvinyl alcohol has good film-forming properties and excellent film-forming mechanical properties. The dopamine can undergo oxidation-self-polymerization in weak alkaline aqueous solution to form polydopamine. Polydopamine has strong adsorption performance, which can make the isolation layer and the slow-release layer have a strong binding force, and show strong stability in the water environment. After the polyvinyl alcohol is mixed with the dopamine, the obtained isolation layer not only has good mechanical strength, but also has a strong binding force with the slow-release layer.

附图说明Description of drawings

图1是本发明实施例1中所述的负载药物的长效防感染抗菌消毒液晶膜的微胶囊的电镜图。Fig. 1 is the electron micrograph of the microcapsule of the long-acting anti-infection antibacterial disinfection liquid crystal film loaded with medicine described in Example 1 of the present invention.

具体实施方式Detailed ways

下面将参照附图更详细地描述本公开的示例性实施例。虽然附图中显示了本公开的示例性实施例，然而应当理解，可以以各种形式实现本公开而不应被这里阐述的实施例所限制。相反，提供这些实施例是为了能够更透彻地理解本公开，并且能够将本公开的范围完整的传达给本领域的技术人员。Exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. Although exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be embodied in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided for more thorough understanding of the present disclosure and to fully convey the scope of the present disclosure to those skilled in the art.

实施例1Example 1

本实施例的负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。如图1所示，为本实施例的负载药物的长效防感染抗菌消毒液晶膜的微胶囊的电镜图。The drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film of this embodiment includes a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; the dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; The sustained-release layer is loaded with the antibacterial drugs. As shown in FIG. 1 , it is an electron micrograph of the microcapsules of the drug-loaded long-acting anti-infection, antibacterial and disinfecting liquid crystal film of this embodiment.

所述抗菌药物为聚六亚甲基双胍盐酸盐、甲基苯酚、苄索氯铵、茶多酚按照3:1:1:3的质量比混合而成。The antibacterial drug is prepared by mixing polyhexamethylene biguanide hydrochloride, methylphenol, benzethonium chloride and tea polyphenol according to the mass ratio of 3:1:1:3.

所述敷料层还包括液晶成膜材料；所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。本实施例中，所述敷料层包括如下重量份的原料：The dressing layer also includes a liquid crystal film-forming material; the liquid crystal film-forming material is one of polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester, 2-methacryloyloxyethyl phosphorylcholine or Various. In this embodiment, the dressing layer includes the following raw materials in parts by weight:

抗菌药物    100份；100 copies of antibacterial drugs;

聚乳酸      300份；Polylactic acid 300 parts;

透明质酸    550份。Hyaluronic Acid 550 servings.

所述缓释层包括如下重量份的原料：The slow-release layer includes the following raw materials in parts by weight:

所述隔离层包括如下重量份的原料：The isolation layer includes the following raw materials in parts by weight:

聚乙烯醇   100份Polyvinyl alcohol 100 parts

多巴胺     30份。Dopamine 30 parts.

本实施例所述的负载药物的长效防感染抗菌消毒液晶膜的制备方法，包括如下步骤：The preparation method of the drug-loaded long-acting anti-infection antibacterial disinfection liquid crystal film described in this embodiment comprises the following steps:

(1)取抗菌药物、液晶成膜材料，混合均匀，涂覆成膜，形成敷料层；(1) Take antibacterial drugs and liquid crystal film-forming materials, mix them evenly, and coat them to form a film to form a dressing layer;

(2)取抗菌药物、聚乳酸、透明质酸、聚乙烯亚胺，混合均匀，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，形成缓释层；(2) Take antibacterial drugs, polylactic acid, hyaluronic acid, polyethyleneimine, mix them uniformly to form the first prefabricated solution, and apply the first prefabricated solution on the dressing layer in step (1) Covered into a film to form a slow-release layer;

(3)取聚乙烯醇、多巴胺，混合均匀，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。(3) Take polyvinyl alcohol and dopamine, mix them uniformly to form a second preformed solution, and coat the second preformed solution on the slow-release layer in step (2) to form a film to form an isolation layer.

需要说明的是，步骤(1)-(3)中，可以以水作为溶剂，水的用量并不唯一，在涂覆成膜后，水作为溶剂被挥发，进而形成薄膜。本实施例中，仅提供一种具体的实现方式，水与敷料层的原料重量份数比为10:1；水与缓释层的原料重量份数比为10:1；水与隔离层的原料重量份数比为10:1。为使各实施例之间具有可比性，以下的实施例均采用该用量的水，下文不再赘述。It should be noted that in steps (1)-(3), water can be used as a solvent, and the amount of water used is not unique. After coating and forming a film, water is volatilized as a solvent to form a film. In the present embodiment, only provide a kind of specific implementation mode, the raw material weight and number ratio of water and dressing layer is 10:1; The raw material weight and number ratio of water and slow-release layer is 10:1; Raw material parts by weight ratio is 10:1. In order to make each embodiment comparable, the following embodiments all adopt this amount of water, and will not repeat them below.

所述敷料层、所述缓释层、所述隔离层之间的用量关系也不唯一，本领域技术人员可根据各层的预设厚度确定所述敷料层、所述缓释层、所述隔离层的原料重量份数的比例关系。本实施例中，所述敷料层、所述缓释层、所述隔离层的原料重量份数比为1:3:3。为使各实施例之间具有可比性，以下的实施例均采用该重量份数的用量关系，下文不再赘述。The dosage relationship between the dressing layer, the sustained-release layer, and the isolation layer is not unique, and those skilled in the art can determine the dressing layer, the sustained-release layer, and the The proportion relationship of the raw material parts by weight of the isolation layer. In this embodiment, the ratio of raw materials of the dressing layer, the slow-release layer and the isolation layer is 1:3:3. In order to make the various embodiments comparable, the following embodiments all adopt the dosage relationship of the parts by weight, which will not be described in detail below.

实施例2Example 2

本实施例的负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。The drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film of this embodiment includes a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; the dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; The sustained-release layer is loaded with the antibacterial drugs.

所述抗菌药物为枸橼酸、甲基苯酚、苄索氯铵、茶多酚按照1:1:1:3的质量比混合而成。The antibacterial drug is prepared by mixing citric acid, methylphenol, benzethonium chloride and tea polyphenols in a mass ratio of 1:1:1:3.

所述敷料层还包括液晶成膜材料；所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。本实施例中，所述敷料层包括如下重量份的原料：The dressing layer also includes a liquid crystal film-forming material; the liquid crystal film-forming material is one of polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester, 2-methacryloyloxyethyl phosphorylcholine or Various. In this embodiment, the dressing layer includes the following raw materials in parts by weight:

抗菌药物    100份；100 copies of antibacterial drugs;

聚乳酸      500份；Polylactic acid 500 parts;

透明质酸    600份。Hyaluronic Acid 600 parts.

所述缓释层包括如下重量份的原料：The slow-release layer includes the following raw materials in parts by weight:

所述隔离层包括如下重量份的原料：The isolation layer includes the following raw materials in parts by weight:

聚乙烯醇   100份Polyvinyl alcohol 100 parts

多巴胺     20份。Dopamine 20 servings.

本实施例所述的负载药物的长效防感染抗菌消毒液晶膜的制备方法，包括如下步骤：The preparation method of the drug-loaded long-acting anti-infection antibacterial disinfection liquid crystal film described in this embodiment comprises the following steps:

(1)取抗菌药物、液晶成膜材料，混合均匀，涂覆成膜，形成敷料层；(1) Take antibacterial drugs and liquid crystal film-forming materials, mix them evenly, and coat them to form a film to form a dressing layer;

(2)取抗菌药物、聚乳酸、透明质酸、聚乙烯亚胺，混合均匀，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，形成缓释层；(2) Take antibacterial drugs, polylactic acid, hyaluronic acid, polyethyleneimine, mix them uniformly to form the first prefabricated solution, and apply the first prefabricated solution on the dressing layer in step (1) Covered into a film to form a slow-release layer;

(3)取聚乙烯醇、多巴胺，混合均匀，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。(3) Take polyvinyl alcohol and dopamine, mix them uniformly to form a second preformed solution, and coat the second preformed solution on the slow-release layer in step (2) to form a film to form an isolation layer.

实施例3Example 3

本实施例的负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。The drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film of this embodiment includes a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; the dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; The sustained-release layer is loaded with the antibacterial drugs.

所述抗菌药物为聚六亚甲基双胍盐酸盐、枸橼酸、甲基苯酚、苄索氯铵按照3:1:1:1的质量比混合而成。The antibacterial drug is prepared by mixing polyhexamethylene biguanide hydrochloride, citric acid, methylphenol, and benzethonium chloride according to a mass ratio of 3:1:1:1.

所述敷料层还包括液晶成膜材料；所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。本实施例中，所述敷料层包括如下重量份的原料：The dressing layer also includes a liquid crystal film-forming material; the liquid crystal film-forming material is one of polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester, 2-methacryloyloxyethyl phosphorylcholine or Various. In this embodiment, the dressing layer includes the following raw materials in parts by weight:

抗菌药物    100份；100 copies of antibacterial drugs;

聚乳酸      400份；Polylactic acid 400 parts;

透明质酸    500份。Hyaluronic Acid 500 servings.

所述缓释层包括如下重量份的原料：The slow-release layer includes the following raw materials in parts by weight:

所述隔离层包括如下重量份的原料：The isolation layer includes the following raw materials in parts by weight:

聚乙烯醇   100份Polyvinyl alcohol 100 parts

多巴胺     10份。Dopamine 10 servings.

本实施例所述的负载药物的长效防感染抗菌消毒液晶膜的制备方法，包括如下步骤：The preparation method of the drug-loaded long-acting anti-infection antibacterial disinfection liquid crystal film described in this embodiment comprises the following steps:

(1)取抗菌药物、液晶成膜材料，混合均匀，涂覆成膜，形成敷料层；(1) Take antibacterial drugs and liquid crystal film-forming materials, mix them evenly, and coat them to form a film to form a dressing layer;

(2)取抗菌药物、聚乳酸、透明质酸、聚乙烯亚胺，在75℃下，搅拌25min，混合均匀，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，形成缓释层；(2) Take antibacterial drugs, polylactic acid, hyaluronic acid, and polyethyleneimine, stir at 75°C for 25 minutes, mix well to form the first preformed solution, and put the first preformed solution in step (1) Coating film-forming on the dressing layer to form a slow-release layer;

(3)取聚乙烯醇、多巴胺，在75℃下，搅拌20min，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。(3) Take polyvinyl alcohol and dopamine, stir at 75°C for 20 minutes to form a second prefabricated solution, and coat the second prefabricated solution on the slow-release layer in step (2) to form a film , forming an isolation layer.

实施例4Example 4

本实施例的负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。The drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film of this embodiment includes a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; the dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; The sustained-release layer is loaded with the antibacterial drugs.

所述抗菌药物为聚六亚甲基双胍盐酸盐、枸橼酸、甲基苯酚、苄索氯铵、茶多酚按照3:1:1:1:3的质量比混合而成。The antibacterial drug is prepared by mixing polyhexamethylene biguanide hydrochloride, citric acid, methylphenol, benzethonium chloride and tea polyphenol according to the mass ratio of 3:1:1:1:3.

所述敷料层还包括液晶成膜材料；所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。本实施例中，所述敷料层包括如下重量份的原料：The dressing layer also includes a liquid crystal film-forming material; the liquid crystal film-forming material is one of polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester, 2-methacryloyloxyethyl phosphorylcholine or Various. In this embodiment, the dressing layer includes the following raw materials in parts by weight:

所述缓释层包括如下重量份的原料：The slow-release layer includes the following raw materials in parts by weight:

所述发泡剂为碳酸氢钠。Described whipping agent is sodium bicarbonate.

所述隔离层包括如下重量份的原料：The isolation layer includes the following raw materials in parts by weight:

聚乙烯醇   100份Polyvinyl alcohol 100 parts

多巴胺     10份。Dopamine 10 servings.

本实施例所述的负载药物的长效防感染抗菌消毒液晶膜的制备方法，包括如下步骤：The preparation method of the drug-loaded long-acting anti-infection antibacterial disinfection liquid crystal film described in this embodiment comprises the following steps:

(1)取抗菌药物、液晶成膜材料，在65℃下，搅拌30min，涂覆成膜，形成敷料层；(1) Take antibacterial drugs and liquid crystal film-forming materials, stir at 65°C for 30 minutes, coat and form a film, and form a dressing layer;

(2)取抗菌药物、聚乳酸、聚酰亚胺、透明质酸、聚酰亚胺、发泡剂，在25℃下，搅拌30min，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，并在55℃下，固化3h，形成缓释层；(2) Take antibacterial drugs, polylactic acid, polyimide, hyaluronic acid, polyimide, and foaming agent, and stir for 30 minutes at 25°C to form a first prefabricated solution, and prepare the first prefabricated solution Coating and forming a film on the dressing layer in step (1), and curing at 55°C for 3 hours to form a slow-release layer;

(3)取聚乙烯醇、多巴胺，在80℃下，搅拌25min，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。(3) Take polyvinyl alcohol and dopamine, stir at 80°C for 25 minutes to form a second prefabricated solution, and coat the second prefabricated solution on the slow-release layer in step (2) to form a film , forming an isolation layer.

实施例5Example 5

本实施例的负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。The drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film of this embodiment includes a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; the dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; The sustained-release layer is loaded with the antibacterial drugs.

所述抗菌药物为聚六亚甲基双胍盐酸盐、枸橼酸、甲基苯酚、苄索氯铵、茶多酚按照3:1:1:1:3的质量比混合而成。The antibacterial drug is prepared by mixing polyhexamethylene biguanide hydrochloride, citric acid, methylphenol, benzethonium chloride and tea polyphenol according to the mass ratio of 3:1:1:1:3.

所述敷料层还包括液晶成膜材料；所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。本实施例中，所述敷料层包括如下重量份的原料：The dressing layer also includes a liquid crystal film-forming material; the liquid crystal film-forming material is one of polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester, 2-methacryloyloxyethyl phosphorylcholine or Various. In this embodiment, the dressing layer includes the following raw materials in parts by weight:

所述缓释层包括如下重量份的原料：The slow-release layer includes the following raw materials in parts by weight:

所述发泡剂为碳酸氢钠。Described whipping agent is sodium bicarbonate.

所述隔离层包括如下重量份的原料：The isolation layer includes the following raw materials in parts by weight:

聚乙烯醇   100份Polyvinyl alcohol 100 parts

多巴胺     30份。Dopamine 30 parts.

本实施例所述的负载药物的长效防感染抗菌消毒液晶膜的制备方法，包括如下步骤：The preparation method of the drug-loaded long-acting anti-infection antibacterial disinfection liquid crystal film described in this embodiment comprises the following steps:

(1)取抗菌药物、液晶成膜材料，在75℃下，搅拌20min，涂覆成膜，形成敷料层；(1) Take antibacterial drugs and liquid crystal film-forming materials, stir at 75°C for 20 minutes, coat and form a film, and form a dressing layer;

(2)取抗菌药物、聚乳酸、聚酰亚胺、透明质酸、聚酰亚胺、发泡剂，在30℃下，搅拌25min，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，并在65℃下，固化5h，形成缓释层；(2) Take antibacterial drugs, polylactic acid, polyimide, hyaluronic acid, polyimide, and foaming agent, and stir for 25 minutes at 30°C to form the first prefabricated solution, and prepare the first prefabricated solution Coating and forming a film on the dressing layer in step (1), and curing at 65°C for 5 hours to form a slow-release layer;

(3)取聚乙烯醇、多巴胺，在75℃下，搅拌30min，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。(3) Take polyvinyl alcohol and dopamine, stir at 75°C for 30 minutes to form a second prefabricated solution, and coat the second prefabricated solution on the slow-release layer in step (2) to form a film , forming an isolation layer.

实施例6Example 6

本实施例的负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。The drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film of this embodiment includes a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; the dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; The sustained-release layer is loaded with the antibacterial drugs.

所述抗菌药物为聚六亚甲基双胍盐酸盐、枸橼酸、甲基苯酚、苄索氯铵、茶多酚按照3:1:1:1:3的质量比混合而成。The antibacterial drug is prepared by mixing polyhexamethylene biguanide hydrochloride, citric acid, methylphenol, benzethonium chloride and tea polyphenol according to the mass ratio of 3:1:1:1:3.

所述敷料层还包括液晶成膜材料；所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。本实施例中，所述敷料层包括如下重量份的原料：The dressing layer also includes a liquid crystal film-forming material; the liquid crystal film-forming material is one of polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester, 2-methacryloyloxyethyl phosphorylcholine or Various. In this embodiment, the dressing layer includes the following raw materials in parts by weight:

所述缓释层包括如下重量份的原料：The slow-release layer includes the following raw materials in parts by weight:

所述发泡剂为碳酸氢钠。Described whipping agent is sodium bicarbonate.

所述隔离层包括如下重量份的原料：The isolation layer includes the following raw materials in parts by weight:

聚乙烯醇   100份Polyvinyl alcohol 100 parts

多巴胺     20份。Dopamine 20 servings.

本实施例所述的负载药物的长效防感染抗菌消毒液晶膜的制备方法，包括如下步骤：The preparation method of the drug-loaded long-acting anti-infection antibacterial disinfection liquid crystal film described in this embodiment comprises the following steps:

(1)取抗菌药物、液晶成膜材料，在70℃下，搅拌25min，涂覆成膜，形成敷料层；(1) Take antibacterial drugs and liquid crystal film-forming materials, stir at 70°C for 25 minutes, coat and form a film, and form a dressing layer;

(2)取抗菌药物、聚乳酸、聚酰亚胺、透明质酸、聚酰亚胺、发泡剂，在20℃下，搅拌20min，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，并在60℃下，固化4h，形成缓释层；(2) Take antibacterial drugs, polylactic acid, polyimide, hyaluronic acid, polyimide, and foaming agent, and stir for 20 minutes at 20°C to form the first preformed solution, and prepare the first preformed solution Coating and forming a film on the dressing layer in step (1), and curing at 60°C for 4 hours to form a slow-release layer;

(3)取聚乙烯醇、多巴胺，在70℃下，搅拌20min，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。(3) Take polyvinyl alcohol and dopamine, stir at 70°C for 20 minutes to form a second prefabricated solution, and coat the second prefabricated solution on the slow-release layer in step (2) to form a film , forming an isolation layer.

实施例7Example 7

本实施例的负载药物的长效防感染抗菌消毒液晶膜，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。The drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film of this embodiment includes a dressing layer, a slow-release layer, and an isolation layer arranged in sequence; the dressing layer is a liquid crystal with a cell membrane-like structure and contains antibacterial drugs; The sustained-release layer is loaded with the antibacterial drugs.

所述抗菌药物为聚六亚甲基双胍盐酸盐、枸橼酸、甲基苯酚、苄索氯铵、茶多酚按照3:1:1:1:3的质量比混合而成。The antibacterial drug is prepared by mixing polyhexamethylene biguanide hydrochloride, citric acid, methylphenol, benzethonium chloride and tea polyphenol according to the mass ratio of 3:1:1:1:3.

所述敷料层还包括液晶成膜材料；所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。本实施例中，所述敷料层包括如下重量份的原料：The dressing layer also includes a liquid crystal film-forming material; the liquid crystal film-forming material is one of polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester, 2-methacryloyloxyethyl phosphorylcholine or Various. In this embodiment, the dressing layer includes the following raw materials in parts by weight:

所述缓释层包括如下重量份的原料：The slow-release layer includes the following raw materials in parts by weight:

所述发泡剂为碳酸氢钠。Described whipping agent is sodium bicarbonate.

所述隔离层包括如下重量份的原料：The isolation layer includes the following raw materials in parts by weight:

聚乙烯醇   100份Polyvinyl alcohol 100 parts

多巴胺     20份。Dopamine 20 servings.

本实施例所述的负载药物的长效防感染抗菌消毒液晶膜的制备方法，包括如下步骤：The preparation method of the drug-loaded long-acting anti-infection antibacterial disinfection liquid crystal film described in this embodiment comprises the following steps:

(1)取抗菌药物、液晶成膜材料，在70℃下，搅拌30min，涂覆成膜，形成敷料层；(1) Take antibacterial drugs and liquid crystal film-forming materials, stir at 70°C for 30 minutes, coat and form a film, and form a dressing layer;

(2)取抗菌药物、聚乳酸、聚酰亚胺、透明质酸、聚酰亚胺、发泡剂，在30℃下，搅拌30min，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，并在65℃下，固化5h，形成缓释层；(2) Take antibacterial drugs, polylactic acid, polyimide, hyaluronic acid, polyimide, and foaming agent, and stir for 30 minutes at 30°C to form the first preformed solution, and mix the first preformed solution with Coating and forming a film on the dressing layer in step (1), and curing at 65°C for 5 hours to form a slow-release layer;

(3)取聚乙烯醇、多巴胺，在70℃下，搅拌30min，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。(3) Take polyvinyl alcohol and dopamine, stir at 70°C for 30 minutes to form a second preformed solution, and coat the second preformed solution on the slow-release layer in step (2) to form a film , forming an isolation layer.

实施例8Example 8

本实施例的负载药物的长效防感染抗菌消毒液晶膜，与实施例7的原料相同，并采用相同的制备方法，区别仅在于：所述敷料层不包括2-甲基丙烯酰氧乙基磷酸胆碱。The drug-loaded long-acting anti-infection antibacterial and disinfecting liquid crystal film of this embodiment has the same raw materials as in Example 7, and uses the same preparation method, the only difference is that the dressing layer does not include 2-methacryloyloxyethyl Phosphocholine.

实施例9Example 9

本实施例的负载药物的长效防感染抗菌消毒液晶膜，与实施例7的原料相同，并采用相同的制备方法，区别仅在于：所述敷料层不包括羟丙基纤维素丙酯。The drug-loaded long-acting anti-infection, anti-bacterial and disinfecting liquid crystal film of this example has the same raw materials as in Example 7, and uses the same preparation method, except that the dressing layer does not include hydroxypropyl cellulose propyl ester.

实施例10Example 10

本实施例的负载药物的长效防感染抗菌消毒液晶膜，与实施例7的原料相同，并采用相同的制备方法，区别仅在于：所述敷料层不包括透明质酸。The drug-loaded long-acting anti-infection, anti-bacterial and disinfecting liquid crystal film of this example has the same raw materials as in Example 7, and uses the same preparation method, the only difference being that the dressing layer does not include hyaluronic acid.

实施例11Example 11

本实施例的负载药物的长效防感染抗菌消毒液晶膜，与实施例7的原料相同，并采用相同的制备方法，区别仅在于：所述缓释层不包括聚酰亚胺。The drug-loaded long-acting anti-infection, antibacterial and disinfecting liquid crystal film of this example has the same raw materials as in Example 7, and uses the same preparation method, with the only difference being that the slow-release layer does not include polyimide.

实施例12Example 12

本实施例的负载药物的长效防感染抗菌消毒液晶膜，与实施例7的原料相同，并采用相同的制备方法，区别仅在于：所述缓释层不包括透明质酸。The drug-loaded long-acting anti-infection, antibacterial and disinfecting liquid crystal film of this example has the same raw materials as in Example 7, and uses the same preparation method, except that the slow-release layer does not include hyaluronic acid.

实施例13Example 13

本实施例的负载药物的长效防感染抗菌消毒液晶膜，与实施例7的原料相同，并采用相同的制备方法，区别仅在于：所述隔离层不包括多巴胺。The drug-loaded long-acting anti-infection, antibacterial and disinfecting liquid crystal film of this embodiment has the same raw materials and the same preparation method as that of Example 7, with the only difference being that the isolation layer does not include dopamine.

实施例14Example 14

本实施例的负载药物的长效防感染抗菌消毒液晶膜，与实施例7的原料相同，并采用相同的制备方法，区别仅在于：所述缓释层不包括3-羟基-2-甲基-4-吡喃酮。The drug-loaded long-acting anti-infection, antibacterial and disinfecting liquid crystal film of this embodiment has the same raw materials as in Example 7, and uses the same preparation method, the only difference is that the slow-release layer does not include 3-hydroxy-2-methyl -4-pyrone.

效果实验例Effect experiment example

为验证本发明所述的负载药物的长效防感染抗菌消毒液晶膜的技术效果，进行以下试验：For verifying the technical effect of the long-acting anti-infection antibacterial disinfection liquid crystal film of load medicine of the present invention, carry out following test:

一、防感染实验1. Anti-infection experiment

取实施例7中的敷料层原料，加入水，所述敷料层原料与水的重量比为1:10，混合均匀，得到样品原液。取样品原液7ml，每管1ml分别接种于需氧-厌氧菌培养管5管与真菌培养管2管，每管含培养基9ml，在其中一支加有样本的需氧-厌氧菌培养管中接种1ml金黄色葡萄球菌稀释悬浮液作为阳性对照。取需氧-厌氧菌培养管与真菌培养管各1支，打开塞放置于试验台上，直至样本无菌检查实验完毕。盖上塞与供试品一起培养，作为阴性对照。将上述接种有样品原液的需氧-厌氧菌培养管、阳性对照管、阴性对照管同时放入32℃的恒温培养箱内，连续培养5d，逐日观察培养结果。Take the dressing layer raw material in Example 7, add water, the weight ratio of the dressing layer raw material to water is 1:10, mix evenly, and obtain the sample stock solution. Take 7ml of sample stock solution, inoculate 1ml of each tube into 5 tubes of aerobic-anaerobic bacteria culture tubes and 2 tubes of fungal culture tubes, each tube contains 9ml of culture medium, and culture aerobic-anaerobic bacteria in one of them with samples Inoculate 1ml of Staphylococcus aureus dilute suspension in the tube as positive control. Take one aerobic-anaerobic culture tube and one fungal culture tube, open the plug and place it on the test bench until the sample sterility test is completed. Cover the plug and incubate with the test product as a negative control. Put the above-mentioned aerobic-anaerobic bacteria culture tubes inoculated with the sample stock solution, positive control tubes, and negative control tubes in a constant temperature incubator at 32°C at the same time, and culture them continuously for 5 days, and observe the culture results every day.

经检测，得到如下结果：After testing, the following results were obtained:

阳性对照管有菌生长，隐形对照管无菌生长，接种所述样品原液的5管需氧-厌氧菌培养管与2管真菌培养管中均无菌生长。The positive control tube had bacterial growth, the invisible control tube had sterile growth, and the 5 tubes of aerobic-anaerobic bacteria culture tubes and 2 tubes of fungal culture tubes inoculated with the sample stock solution grew aseptically.

二、消毒实验2. Disinfection experiment

取实施例7中的敷料层原料，加入水，所述敷料层原料与水的重量比为1:10，混合均匀，得到样品原液。按照《消毒技术规范》(2002版)进行检验。Take the dressing layer raw material in Example 7, add water, the weight ratio of the dressing layer raw material to water is 1:10, mix evenly, and obtain the sample stock solution. According to the "Disinfection Technical Specifications" (2002 edition) for inspection.

经检测，得到如下结果：After testing, the following results were obtained:

经3次重复试验，在20℃恒温试验条件下，应用所述样品原液作用5min，对流感病毒H1N1的灭活对数值均＞4.00、对人类冠状病毒229E的灭活对数值均＞4.00，符合《消毒技术规范》(2002版)消毒合格的规定。After 3 repeated tests, under the constant temperature test conditions of 20°C, the sample stock solution was applied for 5 minutes, and the inactivation logarithms to influenza virus H1N1 were all > 4.00, and the inactivation logarithms to human coronavirus 229E were all > 4.00, which met "Technical Specifications for Disinfection" (2002 Edition) requirements for qualified disinfection.

三、持续抗菌实验3. Continuous antibacterial experiment

取实施例1-14中制备得到的负载药物的长效防感染抗菌消毒液晶膜，进行大肠杆菌、金色葡萄球菌持续抗菌试验：试验菌种为大肠杆菌(8099)(第六代)、金色葡萄球菌(ATCC6538)，购自中国普通微生物菌种保藏管理中心，菌片的含菌量约为9.0×10⁴CFU/片。将所述的负载药物的长效防感染抗菌消毒液晶膜覆盖于载体上，分别常温放置12h、72h，然后分别对大肠杆菌、金色葡萄球菌作用10min，计算杀灭率；其中，杀灭率＝负载药物的长效防感染抗菌消毒液晶膜作用后的含菌量/菌片的含菌量。Get the drug-loaded long-acting anti-infection antibacterial disinfection liquid crystal film prepared in Examples 1-14, carry out E. Cocci (ATCC6538) were purchased from China General Microorganism Culture Collection and Management Center, and the bacteria content in the tablet was about 9.0×10⁴ CFU/tablet. Cover the long-acting anti-infection, antibacterial and disinfection liquid crystal film loaded with drugs on the carrier, place them at room temperature for 12h and 72h respectively, then act on Escherichia coli and Staphylococcus aureus for 10min respectively, and calculate the killing rate; wherein, the killing rate= Bacterial content of the drug-loaded long-acting anti-infection antibacterial and disinfecting liquid crystal film/bacterial content of the bacterial tablet.

四、亲水性实验4. Hydrophilicity experiment

取实施例1-14中制备得到的负载药物的长效防感染抗菌消毒液晶膜，进行亲水性能测试：对所述敷料层进行水接触角测量。The drug-loaded long-acting anti-infection, antibacterial and disinfecting liquid crystal film prepared in Examples 1-14 was used to test the hydrophilic performance: to measure the water contact angle of the dressing layer.

五、粘附性能实验5. Adhesion performance experiment

取实施例1-14中制备得到的负载药物的长效防感染抗菌消毒液晶膜，进行粘附性能测试：将所述敷料层涂覆于第一基板上，将所述缓释层涂覆于所述敷料层上，同时将第二基板覆盖于所述敷料层上，涂层固化后，在所述敷料层、缓释层所在的平面上，沿相反方向的力拉动所述第一基板、第二基板，测试分离所述第一基板、第二基板的力，即为最大剪切力；将最大剪切力除以所述敷料层、缓释层的重叠面积，得到所述敷料层与所述缓释层之间的层间剪切强度W_敷-缓。同样的方法，测试所述缓释层与所述隔离层之间的层间剪切强度W_缓-隔。Take the drug-loaded long-acting anti-infection, antibacterial and disinfection liquid crystal film prepared in Examples 1-14, and carry out the adhesion performance test: the dressing layer is coated on the first substrate, and the slow-release layer is coated on the On the dressing layer, cover the second substrate on the dressing layer at the same time. After the coating is cured, on the plane where the dressing layer and the slow-release layer are located, pull the first substrate, The second substrate, test the force separating the first substrate and the second substrate, which is the maximum shear force; divide the maximum shear force by the overlapping area of the dressing layer and the slow-release layer to obtain the dressing layer and the slow-release layer. The interlaminar shear strength between the sustained-release layers is Wapp_-slow . In the same way, the interlaminar_shear strength W between the slow-release layer and the isolation layer was tested.

经实验，得到如下结果：After experimenting, the following results were obtained:

根据上述结果可以得出如下结论：According to the above results, the following conclusions can be drawn:

(1)本发明所述的负载药物的长效防感染抗菌消毒液晶膜，具有良好的防感染、消毒、抗菌效果，具有较好的亲水性，能够对伤口渗液起到良好的吸附效果。具有长效抗菌效果，同时敷料层、缓释层、隔离层之间具有良好的粘附性能，不易分层脱落，能够满足长时间的使用要求。(1) The drug-loaded long-acting anti-infection antibacterial disinfection liquid crystal film of the present invention has good anti-infection, disinfection and antibacterial effects, has good hydrophilicity, and can play a good adsorption effect on wound exudate . It has a long-lasting antibacterial effect, and at the same time, it has good adhesion between the dressing layer, the slow-release layer and the isolation layer, and is not easy to delaminate and fall off, which can meet the long-term use requirements.

(2)根据实施例7与8的对比可知，敷料层不包括2-甲基丙烯酰氧乙基磷酸胆碱，对于材料的亲水性、持续抗菌性能有一定的影响、敷料层与缓释层的结合强度均有一定的影响。(2) According to the comparison of Examples 7 and 8, it can be seen that the dressing layer does not include 2-methacryloyloxyethyl phosphorylcholine, which has a certain impact on the hydrophilicity and continuous antibacterial performance of the material. The bonding strength of the layer has a certain influence.

(3)根据实施例7与9的对比可知，所述敷料层不包括羟丙基纤维素丙酯，对于亲水性能产生较大影响，对于敷料层与缓释层的结合强度也产生较大影响。根据实施例7与10的对比可知，所述敷料层不包括透明质酸，对于持续抗菌性能具有一定的影响，对于亲水性能也产生较大影响。结合实施例1-3的亲水性能可知，羟丙基纤维素丙酯、透明质酸各自对敷料层的亲水性有一定的提升效果，但是两者配合使用时，能够协同提高敷料层的亲水性能，同时，也对持续抗菌性能的提升产生有利影响。(3) According to the comparison of Examples 7 and 9, it can be seen that the dressing layer does not include hydroxypropyl cellulose propyl ester, which has a greater impact on the hydrophilic property, and also has a greater impact on the binding strength of the dressing layer and the slow-release layer. Influence. According to the comparison between Examples 7 and 10, it can be seen that the dressing layer does not include hyaluronic acid, which has a certain impact on the continuous antibacterial performance and has a greater impact on the hydrophilic performance. In conjunction with the hydrophilic properties of Examples 1-3, it can be seen that hydroxypropyl cellulose propyl ester and hyaluronic acid each have a certain promotion effect on the hydrophilicity of the dressing layer, but when the two are used in conjunction, they can synergistically improve the hydrophilicity of the dressing layer. Hydrophilic properties, at the same time, also have a favorable effect on the improvement of sustained antimicrobial properties.

(4)根据实施例7与11的对比可知，所述缓释层不包括聚酰亚胺，对于持续抗菌性能产生显著影响，对于隔离层与缓释层的结合强度、敷料层与缓释层的结合强度也具有显著影响。(4) According to the comparison of Examples 7 and 11, it can be seen that the slow-release layer does not include polyimide, which has a significant impact on the continuous antibacterial performance, and for the bonding strength of the isolation layer and the slow-release layer, the dressing layer and the slow-release layer The bond strength also has a significant effect.

(5)根据实施例7与12的对比可知，所述缓释层不包括透明质酸，对于持续抗菌性能具有一定的影响，并且对于隔离层与缓释层的结合强度有显著的影响，对于敷料层与缓释层的结合强度影响可以忽略。另外，根据实施例7与13的对比可知，隔离层不包括多巴胺，对于隔离层与缓释层的结合强度有显著的影响。可见，缓释层添加透明质酸、隔离层添加多巴胺，可以使隔离层、缓释层之间的粘附性能大大提升。(5) According to the comparison of Examples 7 and 12, it can be seen that the slow-release layer does not include hyaluronic acid, which has a certain impact on the sustained antibacterial performance, and has a significant impact on the bonding strength of the isolation layer and the slow-release layer. The influence of the binding strength between the dressing layer and the sustained-release layer can be ignored. In addition, according to the comparison of Examples 7 and 13, it can be seen that the isolation layer does not contain dopamine, which has a significant impact on the bonding strength between the isolation layer and the sustained-release layer. It can be seen that adding hyaluronic acid to the slow-release layer and adding dopamine to the isolation layer can greatly improve the adhesion between the isolation layer and the sustained-release layer.

(6)根据实施例7与14的对比可知，所述缓释层不包括3-羟基-2-甲基-4-吡喃酮，对于持续抗菌性能具有较大影响。(6) According to the comparison of Examples 7 and 14, it can be seen that the slow-release layer does not include 3-hydroxy-2-methyl-4-pyrone, which has a greater impact on the sustained antibacterial performance.

以上所述是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明所述原理的前提下，还可以作出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。The above description is a preferred embodiment of the present invention, it should be pointed out that for those of ordinary skill in the art, without departing from the principle of the present invention, some improvements and modifications can also be made, and these improvements and modifications can also be made. It should be regarded as the protection scope of the present invention.

Claims (10)

Translated fromChinese

1.一种负载药物的长效防感染抗菌消毒液晶膜，其特征在于，包括依次设置的敷料层、缓释层、隔离层；所述敷料层为具有仿细胞膜结构的液晶体，且含有抗菌药物；所述缓释层负载有所述抗菌药物。1. a long-acting anti-infection antibacterial disinfection liquid crystal film of load medicine, it is characterized in that, comprises dressing layer, sustained-release layer, isolation layer that are arranged successively; Described dressing layer is the liquid crystal with imitation cell membrane structure, and contains antibacterial Medicine; the sustained-release layer is loaded with the antibacterial medicine.2.根据权利要求1所述的负载药物的长效防感染抗菌消毒液晶膜，其特征在于，所述抗菌药物为聚六亚甲基双胍盐酸盐、枸橼酸、甲基苯酚、苄索氯铵、茶多酚中的一种或多种。2. the long-acting anti-infection antibacterial disinfection liquid crystal film of loading drug according to claim 1, is characterized in that, described antibacterial drug is polyhexamethylene biguanide hydrochloride, citric acid, methylphenol, benzyl One or more of ammonium chloride and tea polyphenols.3.根据权利要求2所述的负载药物的长效防感染抗菌消毒液晶膜，其特征在于，所述敷料层还包括液晶成膜材料；3. the long-acting anti-infection antibacterial disinfection liquid crystal film of loading medicine according to claim 2, is characterized in that, described dressing layer also comprises liquid crystal film-forming material;所述液晶成膜材料为聚乳酸、透明质酸、羟丙基纤维素丙酯、2-甲基丙烯酰氧乙基磷酸胆碱中的一种或多种。The liquid crystal film-forming material is one or more of polylactic acid, hyaluronic acid, hydroxypropyl cellulose propyl ester, and 2-methacryloyloxyethyl phosphorylcholine.4.根据权利要求3所述的负载药物的长效防感染抗菌消毒液晶膜，其特征在于，所述敷料层包括如下重量份的原料：4. the long-acting anti-infection antibacterial disinfection liquid crystal film of loading medicine according to claim 3, is characterized in that, described dressing layer comprises the raw material of following weight portion:抗菌药物     100份；100 copies of antibacterial drugs;聚乳酸       300-500份；Polylactic acid 300-500 parts;透明质酸     500-600份。Hyaluronic acid 500-600 parts.5.根据权利要求1所述的负载药物的长效防感染抗菌消毒液晶膜，其特征在于，所述缓释层包括聚乙烯亚胺；或者，5. The long-acting anti-infection antibacterial disinfection liquid crystal film loaded with medicine according to claim 1, wherein the slow-release layer comprises polyethyleneimine; or,所述缓释层包括聚酰亚胺、发泡剂。The slow-release layer includes polyimide and foaming agent.6.根据权利要求5所述的负载药物的长效防感染抗菌消毒液晶膜，其特征在于，所述缓释层包括如下重量份的原料：6. the long-acting anti-infection antibacterial disinfection liquid crystal film of drug load according to claim 5, is characterized in that, described slow-release layer comprises the raw material of following weight portion:抗菌药物     100份；100 copies of antibacterial drugs;聚乳酸       100-300份；Polylactic acid 100-300 parts;透明质酸     200-300份；Hyaluronic acid 200-300 parts;聚乙烯亚胺   100-200份。Polyethyleneimine 100-200 parts.7.根据权利要求5所述的负载药物的长效防感染抗菌消毒液晶膜，其特征在于，所述缓释层包括如下重量份的原料：7. the long-acting anti-infection antibacterial disinfection liquid crystal film of loading medicine according to claim 5, is characterized in that, described slow-release layer comprises the raw material of following weight portion:抗菌药物     100份；100 copies of antibacterial drugs;聚乳酸       50-100份；Polylactic acid 50-100 parts;透明质酸     180-240份；Hyaluronic acid 180-240 parts;聚酰亚胺     320-400份；Polyimide 320-400 parts;发泡剂       1-50份。Foaming agent 1-50 parts.8.根据权利要求1所述的负载药物的长效防感染抗菌消毒液晶膜，其特征在于，所述隔离层包括聚乙烯醇、多巴胺中的一种或多种。8. The drug-loaded long-acting anti-infection antibacterial and disinfection liquid crystal film according to claim 1, wherein the isolation layer comprises one or more of polyvinyl alcohol and dopamine.9.根据权利要求8所述的负载药物的长效防感染抗菌消毒液晶膜，其特征在于，所述隔离层包括如下重量份的原料：9. the long-acting anti-infection antibacterial disinfection liquid crystal film of loading medicine according to claim 8, is characterized in that, described isolation layer comprises the raw material of following weight portion:聚乙烯醇     100份；100 parts of polyvinyl alcohol;多巴胺       10-30份。Dopamine 10-30 servings.10.一种权利要求1-9中任意一项所述的负载药物的长效防感染抗菌消毒液晶膜的制备方法，其特征在于，包括如下步骤：10. A preparation method for the long-acting anti-infection antibacterial disinfection liquid crystal film of the load medicine described in any one of claims 1-9, it is characterized in that, comprises the steps:(1)取抗菌药物、液晶成膜材料，混合均匀，涂覆成膜，形成敷料层；(1) Take antibacterial drugs and liquid crystal film-forming materials, mix them evenly, and coat them to form a film to form a dressing layer;(2)取缓释层的原料，混合均匀，形成第一预制液，并将所述第一预制液在步骤(1)中的所述敷料层上进行涂覆成膜，形成缓释层；(2) Take the raw materials of the slow-release layer, mix them uniformly to form a first prefabricated solution, and coat the first prefabricated solution on the dressing layer in step (1) to form a film to form a sustained-release layer;(3)取聚乙烯醇、多巴胺，混合均匀，形成第二预制液，并将所述第二预制液在步骤(2)中的所述缓释层上进行涂覆成膜，形成隔离层。(3) Take polyvinyl alcohol and dopamine, mix them uniformly to form a second preformed solution, and coat the second preformed solution on the slow-release layer in step (2) to form a film to form an isolation layer.

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