CN110755409A - 一种大黄素纳米纤维载药系统及其构建方法和应用 - Google Patents
一种大黄素纳米纤维载药系统及其构建方法和应用 Download PDFInfo
- Publication number
- CN110755409A CN110755409A CN201911074685.3A CN201911074685A CN110755409A CN 110755409 A CN110755409 A CN 110755409A CN 201911074685 A CN201911074685 A CN 201911074685A CN 110755409 A CN110755409 A CN 110755409A
- Authority
- CN
- China
- Prior art keywords
- emodin
- solution
- cellulose acetate
- borneol
- polyvinylpyrrolidone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/24—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/0007—Electro-spinning
- D01D5/0015—Electro-spinning characterised by the initial state of the material
- D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01D5/00—Formation of filaments, threads, or the like
- D01D5/28—Formation of filaments, threads, or the like while mixing different spinning solutions or melts during the spinning operation; Spinnerette packs therefor
- D01D5/30—Conjugate filaments; Spinnerette packs therefor
- D01D5/34—Core-skin structure; Spinnerette packs therefor
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F1/00—General methods for the manufacture of artificial filaments or the like
- D01F1/02—Addition of substances to the spinning solution or to the melt
- D01F1/10—Other agents for modifying properties
- D01F1/103—Agents inhibiting growth of microorganisms
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
- D01F8/02—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from cellulose, cellulose derivatives, or proteins
-
- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
- D01F8/04—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers
- D01F8/10—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers with at least one other macromolecular compound obtained by reactions only involving carbon-to-carbon unsaturated bonds as constituent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Textile Engineering (AREA)
- Materials Engineering (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Mechanical Engineering (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dispersion Chemistry (AREA)
- Dermatology (AREA)
- Manufacturing & Machinery (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明公开了一种大黄素纳米纤维载药系统及其构建方法和应用,所述载药系统是具有壳‑核结构的纳米纤维,所述壳层为冰片/乙酸纤维素,所述核层为大黄素/聚乙烯吡咯烷酮K90。构建方法包括以下步骤:(1)配制冰片和乙酸纤维素壳层电纺溶液;(2)配制大黄素和聚乙烯吡络烷酮K90核层电纺溶液;(3)同轴静电纺丝制得壳‑核层纳米纤维载药系统。本发明将疏水性大黄素以无定形态载入到亲水性聚乙烯吡络烷酮基质为核层,被包裹于冰片和疏水性乙酸纤维基质的壳层中,所制备的壳‑核结构纳米纤维毡,呈现大黄素先速释后缓释的释药特征,具有长效抑制耐加氧西林葡萄球菌的作用。
Description
技术领域
本发明涉及抗菌性纳米纤维医用敷料,具体涉及一种载有大黄素和冰片的壳-核结构纳米纤维膜及其制备方法和在制备长效抗耐药菌药物中的应用。
背景技术
烧伤、创伤及糖尿病溃疡所导致的慢性难愈合创面,给病人和社会带来了沉重经济负担。据报道,美国每年用于治疗慢性创面的医疗支出为250亿美元,并呈逐年增加的趋势;我国慢性创面患者占外科住院患者的1.5-3.0%之多。对于各种难愈合创面的治疗,避免创面感染尤其是耐药菌感染,更是创面愈合要面临的严峻考验。由于抗生素的广泛滥用,导致耐药菌株的大量出现,其中有“超级细菌“之称的耐甲氧西林金黄色葡萄球菌(Methicillin-resistant staphylococcus aureus,MRSA)在临床上最为普遍,其多重耐药、毒性强、易于传播的特点,使MRSA感染成为全球以及中国目前严重的临床及公共卫生问题。
大黄素为广泛存在于大黄、虎杖、何首乌等临床常用中药的一种蒽醌类活性成分,具有泻下、抗菌和抗肿瘤等多种药理活性。现代研究表明,大黄素对金黄色葡萄球菌、痤疮丙酸杆菌、绿脓杆菌和大肠杆菌具有显著的抑制作用,并可以通过破坏细胞膜的完整性,与DNA发生氢键结合,干扰核酸的复制和转录,进而影响蛋白质的合成,对MRSA产生抑制作用。由于大黄素存在几乎不溶于水、口服生物利用度极低,并具有肝肾毒性的问题,限制了其应用开发。针对上述存在的问题,本发明采用同轴静电纺丝技术,构建了壳-核结构的冰片/乙酸纤维素-PVP-K90/大黄素纳米纤维用于新型医用敷料,并呈现长效抑制MRSA的活性。
发明内容
针对上述背景技术中存在的问题,本发明的目的在于提供一种大黄素纳米纤维载药系统及其构建方法和应用。本发明将疏水性大黄素以无定形态载入到亲水性聚乙烯吡络烷酮基质为核层,被包裹于冰片和疏水性乙酸纤维基质的壳层中,所制备的壳-核结构纳米纤维毡,呈现大黄素先速释后缓释的释药特征,具有长效抑制耐加氧西林葡萄球菌的作用。本发明简单易行,所制备的大黄素纳米纤维载药系统可用于创伤医用敷料,且具有长效抗耐药菌性能。
为实现上述发明目的,本发明采用以下技术方案:
一种大黄素纳米纤维载药系统,所述载药系统是具有壳-核结构的纳米纤维,所述壳层为冰片/乙酸纤维素,所述核层为大黄素/聚乙烯吡咯烷酮K90。
上述所述的大黄素纳米纤维载药系统的构建方法,包括以下步骤:
(1)制备冰片/乙酸纤维素溶液,用作同轴静电纺丝的壳层电纺液;
(2)制备大黄素/聚乙烯吡咯烷酮K90溶液,用作同轴静电纺丝的核层电纺液;
(3)将壳层电纺液与核层电纺液经同轴静电纺,制成冰片/乙酸纤维素为壳层,大黄素/聚乙烯吡咯烷酮K90为核层的同轴纳米载药纤维。
进一步地,所述步骤(1)中冰片/乙酸纤维素溶液的制备方法为:将乙酸纤维素溶解于丙酮-N,N-二甲基乙酰胺混合溶液中,搅拌溶解,制得乙酸纤维素溶液;加入冰片,搅拌溶解,制得冰片/乙酸纤维素溶液。
进一步地,所述步骤(1)中冰片/乙酸纤维素溶液的制备方法具体为:称取乙酸纤维素溶于丙酮和N,N-二甲基乙酰胺(DMAC)的混合溶液中,所述丙酮与DMAC的体积比为2:1,搅拌至乙酸纤维素全部溶解,获得浓度为3%~10%的乙酸纤维素溶液(w/v);称取冰片适量放入乙酸纤维素溶液中,搅拌至冰片全部溶解,即制得冰片/乙酸纤维素溶液,其中冰片的添加量为大黄素质量的5%。
进一步地,所述步骤(2)中大黄素/聚乙烯吡咯烷酮K90溶液的制备方法为:将聚乙烯吡咯烷酮K90溶解于丙酮-N,N-二甲基乙酰胺混合溶液中,搅拌溶解,制得聚乙烯吡咯烷酮K90溶液;加入大黄素,搅拌溶解,制得大黄素/聚乙烯吡咯烷酮K90溶液。
进一步地,所述步骤(2)中大黄素/聚乙烯吡咯烷酮K90溶液的制备方法具体为:称取聚乙烯吡咯烷酮K90溶于丙酮-N,N-二甲基乙酰胺混合溶液中,所述丙酮与N,N-二甲基乙酰胺的体积比为2:1,搅拌至聚乙烯吡咯烷酮K90完全溶解,得到浓度为7%~13%的聚乙烯吡咯烷酮K90溶液(w/v);称取大黄素放入聚乙烯吡咯烷酮K90溶液中,搅拌至大黄素完全溶解,即制得大黄素/聚乙烯吡咯烷酮K90溶液,其中大黄素的添加量为大黄素和聚乙烯吡咯烷酮K90总质量的5%~10%。
进一步地,所述步骤(3)中电纺工艺参数为:电纺电压为7~14KV,接收距离为10-20cm,,接受器转速为0-40r/min,壳层、核层溶液流速为0.25~0.45mm/min,温度为25~30℃,相对湿度为48%~67%;优选地,接收距离为12-15cm,接受器转速为20-40r/min。
上述所述的大黄素纳米纤维载药系统在制备长效抗耐药菌药物中的应用。
进一步地,上述所述的大黄素纳米纤维载药系统在制备长效抗耐甲氧西林金黄色葡萄球菌药物中的应用。
一种具有长效抑制耐药菌作用的大黄素纳米载药医用敷料,制备方法如下:将上述制备得到的同轴纳米载药纤维于室温下干燥器中干燥48-96h。
本发明的有益效果为:本发明的大黄素纳米载药系统用于抑制耐甲氧西林金黄色葡萄球菌的生长,可长达10天,具有长效抑制作用。大黄素虽然具有较强的抗菌活性,但其不溶于水、口服生物利用度低的不足,限制了其应用开发,本发明采用同轴静电纺丝技术制备一种新型大黄素载药系统,即以冰片/乙酸纤维素为壳层、大黄素/PVP-K90为核层,电纺出负载大黄素的壳-核结构纳米纤维膜,具高空隙率,能有效促进空气渗透,又能阻挡微生物的感染,吸水性好,尤其显著提高了大黄素的溶解度,抑制耐甲氧西林金黄色葡萄球菌生长的活性显著,长达10天。这些特征均为本发明在慢性创面医用敷料的应用提供了有力支撑。本发明是外用给药,可以降低肝肾毒性。
本发明制备得到的纳米纤维与细胞外基质形态结构相近,便于细胞黏附、扩增及迁移;比表面积高,有望增大疏水性成分大黄素的分散和溶出,进而提高其生物利用度;孔隙率高,透气性好,可有效吸收伤口渗出液。
本发明具有操作简单、载药量和包封率高,成本低、适应性强等特点。
附图说明
图1为本发明实施例提供的以冰片/乙酸纤维素为壳层、8.5%大黄素/PVP-K90为核层的大黄素纳米载药纤维膜扫描电镜图;图a、b分别为放大倍数为1000和5000的电镜图。
图2为本发明实施例提供的以冰片/乙酸纤维素为壳层、8.5%大黄素/PVP-K90为核层的大黄素纳米载药纤维膜透射电镜图。
图3为本发明实施例提供的以乙酸纤维素为壳层、8.5%大黄素/PVP-K90为核层的大黄素纳米载药纤维膜扫描电镜图;图a、b、c分别为放大倍数为500、1000和5000的电镜图。
图4为本发明实施例提供的以冰片/乙酸纤维素为壳层、7%大黄素/PVP-K90为核层的大黄素纳米载药纤维膜扫描电镜图;图a、b分别为放大倍数为1000和5000的电镜图。
图5为本发明实施例提供的以冰片/乙酸纤维素为壳层、PVP-K90为核层的空白纳米纤维膜扫描电镜图;图a、b分别为放大倍数为1000和5000的电镜图。
图6为本发明实施例提供的培养基均匀接种耐甲氧西林金黄色葡萄球菌悬液后贴敷纤维膜24h后形成的抑菌区域图。
图7为本发明实施例提供的培养基均匀接种耐甲氧西林金黄色葡萄球菌悬液后贴敷纤维膜10day后形成的抑菌区域图。
图8为本发明实施例提供的培养基划线接种耐甲氧西林金黄色葡萄球菌悬液后贴敷纤维膜24h后形成的抑菌区域图。
图9为本发明实施例提供的培养基划线接种耐甲氧西林金黄色葡萄球菌悬液后贴敷纤维膜10day后形成的抑菌区域图。
具体实施方式
下面将结合本发明具体实施例并对照附图更加清晰完整地阐述本发明的目的、构建方案及应用,但本发明所描述的实施例只是本发明的一部分实例,而不是全部实例,仅用于说明本发明,而不应视为限制本发明的范围。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护范围。
溶剂及电纺参数对于本发明的影响如下:
溶液可纺性和纤维形貌计分:
能连续电纺、纤维形貌均一、表面光滑、无串珠,计分为10分;基本能连续电纺、纤维形貌基本均一,表面基本光滑、有少量串珠,记分为8-9分;喷头有液滴聚集、断续电纺、纤维形貌部分不均一、表面部分不光滑,有部分串珠,记分6-7分;喷头有大量液滴聚集、只能喷丝、纤维形貌基本不均一、表面基本不光滑,有大量串珠,记分3-5分;溶剂不能溶解基质或能溶解但是完全不能电纺,均记为0分。
1.电纺溶剂的选择
1.1核层溶剂的选择:无水乙醇能溶解核层基质PVP-K90,但是不能溶解大黄素,加入0.2%DMSO后能溶解大黄素,但是不能电纺。
1.2壳层溶剂的选择:丙酮中不能溶解,丙酮/DMAC(1:1)较难溶解,丙酮/DMAC(2:1)能溶解
2.基质浓度和药物浓度对纤维成型和形貌的影响
基质浓度影响着纤维的形貌以及壳、核层的厚度,所以在确定丙酮/DMAC(2:1,v/v)为壳层、核层的溶剂后,进一步优化基质浓度对纤维形貌的影响。
2.1壳层CA溶液浓度对纤维形貌的影响
2.2核层PVP-90溶液浓度对纤维形貌的影响
2.3大黄素浓度对纤维成型和形貌的影响
大黄素为疏水性化合物,不溶于水,在丙酮/DMAC(2:1)混合溶剂中能溶解,PVP-K90有很好的分散性以及增溶性,能使大黄素的分散度与溶解度增大,在保证纤维形貌良好的前提下,载药量随着PVP-K90溶液浓度的增大而提高。
3.壳层、核层溶液流速对纤维成型和形貌的影响
核层基质PVP90电纺性好,其流速对于纤维形貌影响无影响。主要考察壳层溶液的流速对纤维形貌的影响。
以5%冰片-3%CA为壳层,7%大黄素-13%PVPK90为核层,电压为11.00kv条件下,考察壳层、核层溶液的流速对纤维形貌的影响。
4.电压对纤维成型和形貌的影响
本发明实施例如下:
【实施例1】负载8.5%大黄素的静电纺丝纳米纤维膜制备
于10ml离心管中放入6ml丙酮-DMAC(2:1)混合溶剂,称取0.180g乙酸纤维素溶入混合溶液中,磁力搅拌120min,乙酸纤维素全部溶解;称取0.00362g冰片溶于乙酸纤维素混合溶液中,磁力搅拌5min,冰片溶解,溶液澄清,即制得冰片/乙酸纤维素溶液作为同轴静电纺丝壳层电纺液;移取6ml丙酮-DMAC(2:1)混合溶剂,称取0.780g PVP-K90溶于混合溶液中,磁力搅拌150min,PVP-K90完全溶解;称取0.07218g大黄素溶于PVP-K90溶液中,磁力搅拌120min,大黄素完全溶解,即得8.5%大黄素/PVP-K90溶液作为同轴静电纺丝核层电纺液;将壳液及核液分别装于2ml注射器中,电纺电压为11~12.5KV,接收距离15cm,接受器转速20r/min,壳层、核层流速均为0.3mm/min,温度25~29℃,相对湿度48%~67%的条件下同轴电纺120min,以锡纸作为接收载体,制得以冰片/乙酸纤维素为壳层、8.5%大黄素/PVP-K90为核层的大黄素纳米载药纤维膜,直径为400nm~800nm,主要分布于600~700nm。该大黄素纳米载药纤维膜扫描电镜图如图1所示,透射电镜图如图2所示。扫描电镜结果表明,该电纺溶液和电纺参数条件下,得到的大黄素纳米纤维直径均一,表面光滑无串珠;透射电镜结果表明,该纳米纤维具有清晰的壳-核结构,其中负载大黄素的核层被壳层包裹于正中间。
【实施例2】壳层不含冰片的大黄素静电纺丝纳米纤维膜制备
称取0.181g乙酸纤维素溶于6ml丙酮-DMAC(2:1)混合溶剂中,磁力搅拌120min,乙酸纤维素全部溶解,即制得不含冰片的乙酸纤维素溶液作为同轴静电纺丝壳层电纺液;称取0.781g PVP-K90溶于6ml丙酮-DMAC(2:1)混合溶剂中,磁力搅拌120min,PVP-K90完全溶解;称取0.07213g大黄素溶于PVP-K90溶液中,磁力搅拌150min,大黄素完全溶解,即得8.5%大黄素/PVP-K90溶液作为同轴静电纺丝核层电纺液;将壳液及核液分别装于2ml注射器中,电纺电压为11~12.5KV,接收距离15cm,接受器转速20r/min,壳层、核层流速均为0.3mm/min,温度25~29℃,相对湿度48%~67%的条件下同轴电纺120min,以锡纸作为接收载体,制得以乙酸纤维素为壳层、8.5%大黄素/PVP-K90为核层的大黄素纳米载药纤维膜,直径为500nm~900nm,主要分布于600~700nm。该大黄素纳米载药纤维膜扫描电镜图如图3所示。扫描电镜结果表明,该电纺溶液和电纺参数条件下,得到的大黄素纳米纤维直径均一,表面光滑无串珠;透射电镜结果表明,该纳米纤维具有清晰的壳-核结构,其中负载大黄素的核层被壳层包裹于正中间。
【实施例3】负载7%大黄素的静电纺丝纳米纤维膜制备
称取0.181g乙酸纤维素溶于6ml丙酮-DMAC(2:1)混合溶剂中,磁力搅拌120min,称取0.00292g冰片放入乙酸纤维素混合溶液中,磁力搅拌5min,冰片溶解,即制得冰片/乙酸纤维素溶液作为同轴静电纺丝壳层电纺液;移取3ml丙酮-DMAC(2:1)混合溶剂,称取0.390gPVP-K90放入混合溶液中,磁力搅拌120min,PVP-K90完全溶解;称取0.02936g大黄素溶于PVP-K90溶液中,磁力搅拌120min,大黄素完全溶解,即得7%大黄素/PVP-K90溶液作为同轴静电纺丝核层电纺液;将壳液及核液分别装于2ml注射器中,电纺电压为11~12.5KV,接收距离15cm,接受器转速20r/min,壳层、核层流速均为0.3mm/min,温度25~29℃,相对湿度48%~67%的条件下同轴电纺120min,以锡纸作为接收载体,制得以冰片/乙酸纤维素为壳层、7%大黄素/PVP-K90为核层的大黄素纳米载药纤维膜,直径为500nm~900nm,主要分布于700~800nm。该大黄素纳米载药纤维膜扫描电镜图如图4所示。扫描电镜结果表明,该电纺溶液和电纺参数条件下,得到的大黄素纳米纤维直径均一,表面光滑无串珠;透射电镜结果表明,该纳米纤维具有清晰的壳-核结构,其中负载大黄素的核层被壳层包裹于正中间。
【实施例4】空白纳米纤维膜制备
称取0.180g乙酸纤维素溶于6ml丙酮-DMAC(2:1)混合溶剂中,旋涡120min,称取0.00356g冰片放入乙酸纤维素混合溶液中,旋涡10min,即制得冰片/乙酸纤维素溶液作为同轴静电纺丝壳层电纺液,称取0.390g PVP-K90溶于3ml丙酮-DMAC(2:1)混合溶剂中,旋涡120min,PVP-K90完全溶解,即得PVP-K90溶液作为同轴静电纺丝核层电纺液;将壳液及核液分别装于2ml注射器中,电纺电压为11~12.5KV,接收距离15cm,接受器转速20r/min,壳层、核层流速均为0.3mm/min,温度25~29℃,相对湿度48%~67%的条件下同轴电纺120min,以锡纸作为接收载体,制得以冰片/乙酸纤维素为壳层、PVP-K90为核层的空白纳米纤维膜,直径为500nm~900nm,主要分布于700~800nm。该空白纳米纤维膜扫描电镜图如图5所示。扫描电镜结果表明,该电纺溶液和电纺参数条件下,得到的空白纳米纤维直径均一,表面光滑无串珠;透射电镜结果表明,该纳米纤维具有清晰的壳-核结构,其中核层被壳层包裹于正中间。
【实施例5】大黄素静电纺丝纳米纤维载药系统的体外释药
随机称取实施例1和实施例2制备得到的8.5%大黄素静电纺丝纳米纤维膜和不含冰片的8.5%大黄素静电纺丝纳米纤维膜以及大黄素原料各3份,加入适量的37±1℃的PBS缓冲溶液(pH=7.4),置于37±1℃的水浴锅中恒温,于不同的时间点(1h、2h、4h、8h、12h、48h)取3mL溶液,立即补充同体积的PBS缓冲溶液,以空白辅料PBS溶液为空白溶液,在254nm处测吸光度。计算大黄素静电纺丝纳米纤维膜中大黄素累积释放率,结果以Mean±SD表示,见表1。结果表明,大黄素作为疏水性成分,在PBS溶液中溶出非常有限,并且随着时间延长,逐渐有黄色结晶析出的现象,所以出现48h时的累积释放量降低的趋势。与大黄素原料药相比,本发明载药系统显著提高了大黄素的溶出速度,1h的累积释药量达到80.61%,且48h内呈现缓慢释药的特征,与不加冰片的载药系统相比,冰片的加入延缓了大黄素的累积释放量,尤其在12h内,显著降低了大黄素的释放,有利于维持载药纳米纤维中大黄素的缓释效果。
表1大黄素静电纳米纤维膜累积释放率、大黄素原料累积溶解率(n=3)
【实施例6】大黄素载药纳米纤维膜红外光谱分析及热分析
采用红外光谱分析仪检测大黄素静电纺丝纳米纤维膜的官能团,已知大黄素静电纺丝纳米纤维膜的制备原料有大黄素、PVP-K90、CA、合成冰片;先将实施例1制备得到的大黄素静电纺丝纳米纤维及其原料置于60℃烘箱中烘2h,以空气为空白,采用ART-IR对大黄素纳米纤维膜以及原材料的特征官能团进行分析。
大黄素、合成冰片、PVP-K90、CA、空白纤维膜、实施例1载药纤维膜经由X射线衍射仪与CuK(λ=1.541874nm),于40kV电压及40mA电流,扫描范围为3°至60°,扫描速度为10°/min的条件下获得X射线衍射图谱。
利用差示热量分析仪对实施例1载药纳米纤维膜、空白膜及其原料的热学性能进行分析,试样用量如下2.00mg(冰片),2.33mg(大黄素),5.47mg(CA),2.00mg(PVP-K90),2.43mg(空白纤维膜),2.33mg(载药纤维膜),测试温度范围为20-300℃,一次升温,升温速率为10K/min,以温度为横坐标,DSC为纵坐标作图分析。
综合红外分析、X-射线衍射和热分析,可得大黄素及合成冰片在载药纳米纤维膜中是以无定型形式存在。
【实施例7】大黄素载药纳米纤维膜吸水膨胀指数
截取空白纤维膜及实施例1载药纤维膜各三份,精密称量吸水前纤维膜重量;将纤维膜分别放入20ml PBS溶液(pH=7.4,温度为37℃),浸泡2h、4h、6h、8h、10h、12h、24h、48h;在不同浸泡时间结束后将纤维膜取出,用纸巾吸走多余液体,精密称量浸泡后纤维膜重量;根据公式(Is:吸水膨胀指数;Ws:吸水后膜的重量,Wd:干燥膜的重量)计算空白纤维膜及载药纤维膜吸水膨胀指数Is,空白纤维膜及载药纤维膜吸水膨胀指数,见表2和表3。结果表明,48h内,大黄素静电纺丝纳米纤维膜的吸水膨胀指数达到1.65,而不含大黄素空白纳米膜的吸水膨胀指数只有0.28,提示负载大黄素的纳米纤维膜吸水性能显著优于空白膜,说明本载药纳米纤维膜有利于吸收伤口部位的渗出物,并保持损伤部位的润湿环境。
表2空白纳米纤维膜吸水膨胀指数
表3大黄素载药纳米纤维膜吸水膨胀指数
【实施例8】抑菌区域法检测抑菌效果(均匀接种菌悬液)
采用抑菌区域法进行检测,将耐药金葡菌进行增殖培养,使细菌悬液浓度达到107CFU/ml;剪取面积为2cm×2cm的8.5%大黄素纳米载药纤维膜及空白纳米纤维膜,紫外照射30min灭菌;取30μl细菌悬液均匀接种至甘露醇高盐琼脂培养基表面,再将载药纳米纤维膜及空白纤维膜贴敷于接种菌悬液后的培养基表面;于37℃恒温培养箱中进行培养,在不同培养时间观察纤维膜周围形成的抑菌区域。
结果表明,在培养至10day时,载药纤维膜周围仍有明显的抑菌圈,空白纤维膜则不影响细菌生长;如图6所示为培养24h后形成的抑菌区域,10day抑菌区域如图7所示。
【实施例9】抑菌区域法检测抑菌效果(划线接种菌悬液)
采用抑菌区域法进行检测,将耐药金葡菌进行增殖培养,使细菌悬液浓度达到107CFU/ml;剪取面积为2cm×2cm的8.5%大黄素纳米载药纤维膜及空白纳米纤维膜,紫外照射30min灭菌;用接种环蘸取细菌悬液,于甘露醇高盐琼脂培养基表面以相同间隔进行划线接种,再将载药纳米纤维膜及空白纤维膜贴敷于接种菌悬液后的培养基表面;于37℃恒温培养箱中进行培养,在不同培养时间观察纤维膜周围形成的抑菌区域。
结果表明,在培养至10day时,载药纤维膜周围仍有明显的抑菌圈,空白纤维膜则不影响细菌生长;如图8所示为培养24h后形成的抑菌区域,10day后抑菌区域如图9所示。综上所述,本发明提供了一种以同轴静电纺丝技术构建大黄素纳米载药系统的方法,同时检测了该给药系统的抗菌活性;结果表明,负载大黄素的纳米纤维膜表现出长效的抗耐甲氧西林金黄色葡萄球菌活性。
Claims (10)
1.一种大黄素纳米纤维载药系统,其特征在于,所述载药系统是具有壳-核结构的纳米纤维,所述壳层为冰片/乙酸纤维素,所述核层为大黄素/聚乙烯吡咯烷酮K90。
2.如权利要求1所述的大黄素纳米纤维载药系统的构建方法,其特征在于,包括以下步骤:
(1)制备冰片/乙酸纤维素溶液,用作同轴静电纺丝的壳层电纺液;
(2)制备大黄素/聚乙烯吡咯烷酮K90溶液,用作同轴静电纺丝的核层电纺液;
(3)将壳层电纺液与核层电纺液经同轴静电纺,制成冰片/乙酸纤维素为壳层,大黄素/聚乙烯吡咯烷酮K90为核层的同轴纳米载药纤维。
3.如权利要求2所述的构建方法,其特征在于,所述步骤(1)中冰片/乙酸纤维素溶液的制备方法为:将乙酸纤维素溶解于丙酮-N,N-二甲基乙酰胺混合溶液中,搅拌溶解,制得乙酸纤维素溶液;加入冰片,搅拌溶解,制得冰片/乙酸纤维素溶液。
4.如权利要求3所述的构建方法,其特征在于,所述步骤(1)中冰片/乙酸纤维素溶液的制备方法具体为:称取乙酸纤维素溶于丙酮和N,N-二甲基乙酰胺的混合溶液中,所述丙酮与N,N-二甲基乙酰胺的体积比为2:1,搅拌至乙酸纤维素全部溶解,获得浓度为3%~10%的乙酸纤维素溶液(w/v);称取冰片适量放入乙酸纤维素溶液中,搅拌至冰片全部溶解,即制得冰片/乙酸纤维素溶液,所述冰片的添加量为大黄素质量的5%。
5.如权利要求2所述的构建方法,其特征在于,所述步骤(2)中大黄素/聚乙烯吡咯烷酮K90溶液的制备方法为:将聚乙烯吡咯烷酮K90溶解于丙酮-N,N-二甲基乙酰胺混合溶液中,搅拌溶解,制得聚乙烯吡咯烷酮K90溶液;加入大黄素,搅拌溶解,制得大黄素/聚乙烯吡咯烷酮K90溶液。
6.如权利要求5所述的构建方法,其特征在于,所述步骤(2)中大黄素/聚乙烯吡咯烷酮K90溶液的制备方法具体为:称取聚乙烯吡咯烷酮K90溶于丙酮-N,N-二甲基乙酰胺混合溶液中,所述丙酮与N,N-二甲基乙酰胺的体积比为2:1,搅拌至聚乙烯吡咯烷酮K90完全溶解,得到浓度为7%~13%的聚乙烯吡咯烷酮K90溶液(w/v);称取大黄素放入聚乙烯吡咯烷酮K90溶液中,搅拌至大黄素完全溶解,即制得大黄素/聚乙烯吡咯烷酮K90溶液,所述大黄素的添加量为大黄素和聚乙烯吡咯烷酮K90总质量的5%~10%。
7.如权利要求2所述的构建方法,其特征在于,所述步骤(3)中电纺工艺参数为:电纺电压为7~14KV,接收距离为10-20cm,接受器转速为0-40r/min,壳层、核层溶液流速为0.25~0.45mm/min,温度为25~30℃,相对湿度为48%~67%;;优选地,接收距离为12-15cm,接受器转速为20-40r/min。
8.如权利要求1所述的大黄素纳米纤维载药系统在制备长效抗耐药菌药物中的应用。
9.如权利要求8所述的应用,其特征在于,权利要求1所述的大黄素纳米纤维载药系统在制备长效抗耐甲氧西林金黄色葡萄球菌药物中的应用。
10.一种具有长效抑制耐药菌作用的大黄素纳米载药医用敷料,其特征在于,制备方法如下:将权利要求2中制备得到的同轴纳米载药纤维于室温下干燥器中干燥48-96h。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911074685.3A CN110755409B (zh) | 2019-11-06 | 2019-11-06 | 一种大黄素纳米纤维载药系统及其构建方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911074685.3A CN110755409B (zh) | 2019-11-06 | 2019-11-06 | 一种大黄素纳米纤维载药系统及其构建方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110755409A true CN110755409A (zh) | 2020-02-07 |
CN110755409B CN110755409B (zh) | 2020-11-10 |
Family
ID=69335856
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911074685.3A Active CN110755409B (zh) | 2019-11-06 | 2019-11-06 | 一种大黄素纳米纤维载药系统及其构建方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110755409B (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112461716A (zh) * | 2020-10-29 | 2021-03-09 | 四川省肿瘤医院 | 大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法 |
CN114271267A (zh) * | 2021-12-06 | 2022-04-05 | 盐城工学院 | 一种农药传递系统及其制备方法 |
CN114644817A (zh) * | 2020-12-21 | 2022-06-21 | 上海紫丹食品包装印刷有限公司 | 一种抗菌可降解薄膜材料及其制备方法和应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104491932A (zh) * | 2014-12-04 | 2015-04-08 | 上海工程技术大学 | 核/壳结构载药纳米防粘连膜及其制备方法 |
-
2019
- 2019-11-06 CN CN201911074685.3A patent/CN110755409B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104491932A (zh) * | 2014-12-04 | 2015-04-08 | 上海工程技术大学 | 核/壳结构载药纳米防粘连膜及其制备方法 |
Non-Patent Citations (3)
Title |
---|
M.M. CASTILLO-ORTEGA等: "Amoxicillin embedded in cellulose acetate-poly (vinyl pyrrolidone) fibers prepared by coaxial electrospinning: Preparation and characterization", 《MATERIALS LETTERS 》 * |
叶惠娴: "天然冰片及合成冰片对大黄素透皮吸收的影响", 《中国药学杂志》 * |
朱文忠等: "同轴静电纺丝法制备大黄素缓释材料治疗牙周炎的初步研究", 《牙体牙髓牙周病学杂志》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112461716A (zh) * | 2020-10-29 | 2021-03-09 | 四川省肿瘤医院 | 大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法 |
CN112461716B (zh) * | 2020-10-29 | 2024-03-22 | 四川省肿瘤医院 | 大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法 |
CN114644817A (zh) * | 2020-12-21 | 2022-06-21 | 上海紫丹食品包装印刷有限公司 | 一种抗菌可降解薄膜材料及其制备方法和应用 |
CN114271267A (zh) * | 2021-12-06 | 2022-04-05 | 盐城工学院 | 一种农药传递系统及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN110755409B (zh) | 2020-11-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110755409B (zh) | 一种大黄素纳米纤维载药系统及其构建方法和应用 | |
Ali et al. | Antibacterial bi-layered polyvinyl alcohol (PVA)-chitosan blend nanofibrous mat loaded with Azadirachta indica (neem) extract | |
Jiji et al. | Thymol enriched bacterial cellulose hydrogel as effective material for third degree burn wound repair | |
Pourhojat et al. | Evaluation of poly ε-caprolactone electrospun nanofibers loaded with Hypericum perforatum extract as a wound dressing | |
Unnithan et al. | Wound-dressing materials with antibacterial activity from electrospun polyurethane–dextran nanofiber mats containing ciprofloxacin HCl | |
CN109731121B (zh) | 一种含有介孔二氧化硅的纤维素和壳聚糖复合敷料的制备方法 | |
CN109908392A (zh) | 一种新型不对称可润湿性静电纺丝双层膜及其制备方法 | |
CN101927029B (zh) | 一种含纳米银的壳聚糖/聚乙烯醇海绵敷料的制备方法 | |
CN107693835A (zh) | 一种聚乙烯醇/胶原蛋白/季铵化壳聚糖静电纺丝复合纤维膜及其制备方法 | |
CN115154642B (zh) | 一种仿生非对称海绵敷料及其制备方法 | |
CN102302458A (zh) | 一种左氧氟沙星缓释微球和长效缓释创伤敷料及制备方法 | |
WO2022105091A1 (zh) | 一种小檗碱/矿化胶原复合膜及其制备方法和应用 | |
CN113786512B (zh) | 一种低压式原位抑菌促修复电纺敷料及其制备方法 | |
CN108716115B (zh) | 抗菌纤维、制备方法及其应用 | |
CN113699696A (zh) | 一种采用便携电纺丝技术制备的多层功能化伤口敷料 | |
Ge et al. | Sabina chinensis leaf extracted and in situ incorporated polycaprolactone/polyvinylpyrrolidone electrospun microfibers for antibacterial application | |
CN107335089A (zh) | 一种改性亲水性聚氨酯敷料及其制备方法 | |
Li et al. | Chitosan-based antibacterial microspheres loaded multifunctional Janus composite membranes with unidirectional biofluid transport, antioxidant and pH-responsive monitoring | |
Liao et al. | “Sandwich-like” structure electrostatic spun micro/nanofiber polylactic acid-polyvinyl alcohol-polylactic acid film dressing with metformin hydrochloride and puerarin for enhanced diabetic wound healing | |
CN116077709A (zh) | 一种抗菌性敷料及其制备方法和应用 | |
CN108997621B (zh) | 一种用缓冲溶液保护的介孔二氧化硅与纤维素共混膜及其制备方法和应用 | |
CN114917394B (zh) | 一种双层载纳米银和生长因子的复合功能性敷料及其制备方法 | |
CN116115816A (zh) | 一种可视化诊断和差别化释药纳米纤维膜的制备方法 | |
CN100547000C (zh) | 一种胡蜂抗菌肽及其制备方法和应用 | |
CN112251912B (zh) | 一种刺山柑载药纳米纤维膜及其制备方法和应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |