WO2019091150A1 - 一种藻酸盐创面修复敷料及其制备方法 - Google Patents

一种藻酸盐创面修复敷料及其制备方法 Download PDF

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Publication number
WO2019091150A1
WO2019091150A1 PCT/CN2018/098243 CN2018098243W WO2019091150A1 WO 2019091150 A1 WO2019091150 A1 WO 2019091150A1 CN 2018098243 W CN2018098243 W CN 2018098243W WO 2019091150 A1 WO2019091150 A1 WO 2019091150A1
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Prior art keywords
alginate
honey
fiber
powder
weight
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PCT/CN2018/098243
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English (en)
French (fr)
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韦加娜
陈锦涛
熊亮
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广东泰宝医疗科技股份有限公司
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Priority to EP18875076.4A priority Critical patent/EP3695855A4/en
Publication of WO2019091150A1 publication Critical patent/WO2019091150A1/zh

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    • 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
    • A61L15/44—Medicaments
    • 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
    • A61L15/18—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic 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
    • A61L15/28—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
    • A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
    • 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
    • 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
    • A61L15/60—Liquid-swellable gel-forming materials, e.g. super-absorbents
    • 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
    • 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
    • D01F9/00—Artificial filaments or the like of other substances; Manufacture thereof; Apparatus specially adapted for the manufacture of carbon filaments
    • D01F9/04—Artificial filaments or the like of other substances; Manufacture thereof; Apparatus specially adapted for the manufacture of carbon filaments of alginates
    • D—TEXTILES; PAPER
    • D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
    • D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
    • D06M11/00—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising
    • D06M11/32—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising with oxygen, ozone, ozonides, oxides, hydroxides or percompounds; Salts derived from anions with an amphoteric element-oxygen bond
    • D06M11/50—Treating fibres, threads, yarns, fabrics or fibrous goods made from such materials, with inorganic substances or complexes thereof; Such treatment combined with mechanical treatment, e.g. mercerising with oxygen, ozone, ozonides, oxides, hydroxides or percompounds; Salts derived from anions with an amphoteric element-oxygen bond with hydrogen peroxide or peroxides of metals; with persulfuric, permanganic, pernitric, percarbonic acids or their salts
    • 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
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/112—Phosphorus-containing compounds, e.g. phosphates, phosphonates
    • 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
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/30—Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • D—TEXTILES; PAPER
    • D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
    • D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
    • D06M2101/00—Chemical constitution of the fibres, threads, yarns, fabrics or fibrous goods made from such materials, to be treated
    • D06M2101/02—Natural fibres, other than mineral fibres
    • D06M2101/04—Vegetal fibres

Definitions

  • the invention relates to the technical field of medical consumables, in particular to an alginate wound repair dressing and a preparation method thereof.
  • a wound is a skin defect caused by mechanical, electrical, thermal, chemical, or the like, or formed by a medical or physiological metamorphosis.
  • Wounds can also be classified according to the pathology, the site of the injury, the cause of the injury, or the color of the wound. In general, depending on the length of healing, it can be divided into acute wounds and chronic wounds.
  • Wound healing refers to the complex process of regeneration and repair after the body tissue has been traumatized. Take the healing process of skin wounds as an example, including the early inflammatory reaction, wound contraction, granulation tissue proliferation and epidermal regeneration. The patient's own physical quality and wound care are different. The specific performance and duration of each stage of the wound healing process are also different, and there are different requirements for the dressing used in the treatment process.
  • Alginate dressing is one of the new dressings formed under the "Wound Wet Healing Theory".
  • the main ingredient is calcium alginate, which is a water-insoluble substance. When it encounters a liquid rich in sodium ions (such as exudate and blood), calcium and sodium ions exchange, calcium ions are released, and sodium ions combine with alginic acid to form a hydrophilic gel. Substance to help the wound maintain a moist environment and enhance autolysis debridement, as well as promote the growth of granulation tissue.
  • a single alginate dressing is difficult to adapt to the care requirements of chronic complex wounds. Therefore, it is combined with other biomedical functional materials to obtain the best quality of wound care. It is currently the development of dressing products. Trends.
  • the purpose of the present invention is to solve the deficiencies of the existing alginate dressings in the care of chronic and complex wounds, and to provide an alginate wound repair capable of analgesic, debridement, bacteriostatic, or sustained function and accelerate wound healing. dressing.
  • the invention relates to an alginate wound repair dressing and a preparation method thereof, which are characterized in that the calcium alginate fiber is processed by complex processing with a biologically active powder, and the weight percentage of the biologically active powder in the dressing is 5-20%.
  • the calcium alginate fiber is a hydrophobically modified alginate fiber, and the processing process is as follows:
  • the bioactive powder is uniformly mixed from the dried honey powder and the bioactive glass powder in a weight ratio of 1:3 to 5.
  • the bioactive glass powder is a 45S5 bioactive glass having a particle size of less than 30 ⁇ m.
  • the method for preparing the dried honey powder is as follows:
  • honey is crystallized and liquefied at 65-80 ° C, and then dehydrated at low temperature until the moisture content of honey is 15 to 25%, and then 0.5 to 3 parts are added.
  • the skin absorption enhancer is fully stirred and uniformly mixed.
  • the transdermal absorption enhancer is composed of any one of synthetic borneol, polyethylene glycol, propylene glycol, vegetable volatile oil, pepper oil, and clove oil.
  • the dressing preparation process is as follows:
  • the fiber processed in the above 3) is cut into short fibers, which are knitted, carded, and needle-punched to form a non-woven fabric, and then the non-woven fabric is cut, packaged, and sterilized to obtain alginic acid.
  • the salt wound repairs the finished dressing.
  • Honey is a complex, nutrient-rich supersaturated sugar solution with extremely high osmotic pressure and low pH. It contains bactericidal components such as hydrogen peroxide and acetone aldehyde. It has a broad spectrum of antibacterial activity and its antibacterial activity. There is no risk of drug resistance. Honey is widely used in wound treatment for its broad-spectrum antibacterial activity and resistance to drug resistance. It can be used not only for the treatment of local acute wound infections, but also for its treatment of refractory wounds. The process of dissolving debridement and promoting tissue growth promotes wound healing.
  • Hydrogen peroxide in honey Hydrogen peroxide is the main substance of honey and has been identified as an "inhibitor” of bacteria, and the peroxidation produced by dilution of honey The harmful effects of hydrogen are reduced, do not damage fibroblasts in human skin, and thus have no side effects on wound healing.
  • High-permeability antibacterial effect of honey The antibacterial property of honey is caused by the osmotic action of its high-sugar component, and it absorbs the pus in the wound and acts as a “clear creation”; when it acts directly on the wound, it forms on the surface. A layer of viscous barrier that prevents fluid loss and prevents bacterial invasion.
  • Acidic antibacterial effect of honey The study found that natural honey is acidic pH 3.2-4.5, and the suitable pH for growth and reproduction of most pathogenic bacteria causing wound infection is 7.0-7.5. Therefore, low concentration honey has antibacterial effect, high Concentration honey has a bactericidal effect.
  • Bioactive glass has unique surface activity as an inorganic biosynthetic material.
  • the unique chemical composition of bioactive glass especially its calcium and phosphorus plasma deposition, forms a scaffold-like hydroxyapatite layer, which makes it have a large specific surface area and is beneficial to cells.
  • Adhesive growth which facilitates the entry of nutrients and oxygen, and the excretion of metabolites, is also conducive to the growth of blood vessels and nerves.
  • Bioactive glass is the only synthetic inorganic material that can promote the formation of growth factors, promote cell proliferation, and activate cell gene expression. It can also continuously induce the epithelial growth factor synthesis of cells themselves, providing patients with their own wounds. The fully biofunctional natural epithelial growth factor plays an important role in the rapid healing of wounds.
  • 45S5 bioactive glass can promote the regeneration of soft tissues such as skin, and the mechanism of accelerating wound healing is as follows: (1) Under the action of body fluids, firstly, active ions such as Na + and Ca 2+ are dissolved, and H + in body fluid enters the glass. The surface forms Si-OH-; (2) due to the destruction of the Si-O-Si bond, the random network is dissolved, the soluble silicon is released in the form of silanol, and a hydroxyapatite cement layer is rapidly formed on the surface of the material powder; (3) Soluble silicon has the metabolic and structural effects of connective tissue at the molecular level.
  • the increase of local Si concentration can promote the internal response of cell metabolism, stimulate the autocrine response of wound healing factor, and participate in wound repair. All of the cells accelerate growth and division under the stimulation of the wound healing factor, and accumulate on the hydroxyapatite cementation layer formed on the surface of the material, so that the new tissue can smoothly climb and cover along the entire wound.
  • the invention can produce the following beneficial effects: the organic combination of the alginate and the honey and the bioactive glass through a certain technology can not only fully exert the high hygroscopicity, hemostatic property and soft gelation property of the alginate in the nursing wound surface ( Non-adhesive wounds), and the three functional materials of alginate, honey, and bioactive glass exhibit organic antibacterial, analgesic, and secretory growth factors to promote wound healing during the wound care, and act as a transdermal absorption enhancer. A synergistic protective effect is created to optimize the care of the wound.
  • the ion exchange of the bioactive glass and the honey during the protection is slowly performed, so that the dressing can continue to exert the effect of protecting the wound, reducing the number of dressings and improving the comfort of the patient. degree.
  • Alginate wound repair dressing using the following preparation process:
  • the fiber processed in the above 3) is cut into short fibers, which are knitted, carded, and needle-punched to form a non-woven fabric, and then the nonwoven fabric is cut, packaged, and sterilized to obtain algae.
  • the acid salt wound repairs the finished dressing.
  • the above bioactive powder is prepared by uniformly mixing the dried honey powder and the bioactive glass powder in a weight ratio of 1:3. Among them, the bioactive glass powder is 45S5 bioactive glass, and its particle diameter is less than 30 ⁇ m.
  • the dried honey powder is prepared by the following method: 1) 60 parts of honey is crystallized and liquefied at 65 ° C in parts by weight, and then dehydrated at a low temperature until the moisture content of the honey is 25%, and then 3 parts of the synthesis is added. The borneol is thoroughly stirred and uniformly mixed; 2) The mixture is placed in a freeze dryer and freeze-dried at minus -20 ° C for 24 hours, and then taken out to form solid honey, and the solid honey layer is pulverized into 100-mesh honey powder.
  • the above hydrophobically modified calcium alginate fiber is obtained by the following processing techniques: (1) Hydrophobic modification of alginate: 2 parts by weight of sodium alginate and 1 part by weight of 1-(in terms of important parts) 3-dimethylaminopropyl)-3-ethylcarbodiimide, 0.5 parts by weight of N-hydroxysuccinimide, sequentially added to 100 parts by weight of a phosphate buffer solution having a pH of 6 at a certain molar ratio After stirring, 100 parts by weight of a methanol solution containing dodecylamine was added, stirred at room temperature for 18 hours, then precipitated with methanol, centrifuged, and the precipitate was dissolved in distilled water, dialyzed for 84 hours, and lyophilized to obtain hydrophobically modified alginic acid.
  • Alginate wound repair dressing using the following preparation process:
  • the fiber processed in the above 3) is cut into short fibers, which are knitted, carded, and needle-punched to form a non-woven fabric, and then the nonwoven fabric is cut, packaged, and sterilized to obtain algae.
  • the acid salt wound repairs the finished dressing.
  • the above bioactive powder is prepared by uniformly mixing the dried honey powder and the bioactive glass powder in a weight ratio of 1:4. Among them, the bioactive glass powder is 45S5 bioactive glass, and its particle diameter is less than 30 ⁇ m.
  • the dried honey powder is prepared by the following method: 1) 50 parts of honey is crystallized and liquefied at 70 ° C in parts by weight, and then dehydrated at a low temperature until the moisture content of the honey is 15%, and then 2 parts of the poly is added. The ethylene glycol was sufficiently stirred and uniformly mixed; 2) The mixture was placed in a freeze dryer and freeze-dried at -40 ° C for 12 hours, and then taken out to form solid honey, and the solid honey layer was pulverized into 60-mesh honey powder.
  • the above hydrophobically modified calcium alginate fiber is obtained by the following processing techniques: (1) Hydrophobic modification of alginate: 3 parts by weight of sodium alginate, 0.5 parts by weight of 1-(in terms of important parts) 3-dimethylaminopropyl)-3-ethylcarbodiimide, 1 part by weight of N-hydroxysuccinimide, sequentially added to 150 parts by weight of a phosphate buffer solution having a pH of 7 at a certain molar ratio After stirring, 80 parts by weight of a methanol solution containing dodecylamine was added, stirred at room temperature for 12 hours, then precipitated with methanol, centrifuged, and the precipitate was dissolved in distilled water, dialyzed for 48 hours, and lyophilized to obtain hydrophobically modified alginic acid.
  • Alginate wound repair dressing using the following preparation process:
  • the fiber processed in the above 3) is cut into short fibers, which are knitted, carded, and needle-punched to form a non-woven fabric, and then the nonwoven fabric is cut, packaged, and sterilized to obtain algae.
  • the acid salt wound repairs the finished dressing.
  • the above bioactive powder is prepared by uniformly mixing the honey dry powder and the bioactive glass powder in a weight ratio of 1:5.
  • the bioactive glass powder is 45S5 bioactive glass, and its particle diameter is less than 30 ⁇ m.
  • the dried honey powder is prepared by the following method: 1) 100 parts of honey is crystallized and liquefied at 75 ° C in parts by weight, and then dehydrated at a low temperature until the moisture content of the honey is 20%, and then 1 part of the plant is added. The volatile oil pepper oil is sufficiently stirred and uniformly mixed; 2) the mixture is placed in a freeze dryer and freeze-dried at minus -30 ° C for 36 hours, and then taken out to form solid honey, and the solid honey layer is pulverized into 300 mesh honey powder.
  • the above hydrophobically modified calcium alginate fiber is obtained by the following processing techniques: (1) Hydrophobic modification of alginate: 4 parts by weight of sodium alginate, 0.6 parts by weight of 1-(by weight) 3-dimethylaminopropyl)-3-ethylcarbodiimide, 0.8 parts by weight of N-hydroxysuccinimide, sequentially added to 200 parts by weight of a phosphate buffer solution having a pH of 6.5 at a certain molar ratio After stirring, the mixture was added to 50 parts by weight of a methanol solution containing dodecylamine, stirred at room temperature for 16 hours, then precipitated with methanol, centrifuged, and the precipitate was dissolved in distilled water, dialyzed for 72 hours, and lyophilized to obtain hydrophobically modified alginic acid.
  • Alginate wound repair dressing using the following preparation process:
  • the fiber processed in the above 3) is cut into short fibers, which are knitted, carded, and needle-punched to form a non-woven fabric, and then the nonwoven fabric is cut, packaged, and sterilized to obtain algae.
  • the acid salt wound repairs the finished dressing.
  • the above bioactive powder is prepared by uniformly mixing the dried honey powder and the bioactive glass powder in a weight ratio of 1:4. Among them, the bioactive glass powder is 45S5 bioactive glass, and its particle diameter is less than 30 ⁇ m.
  • the dried honey powder is prepared by the following method: 1) 80 parts of honey is crystallized and liquefied at 80 ° C in parts by weight, and then dehydrated at a low temperature until the moisture content of the honey is 18%, and then 0.5 parts of clove is added. The oil was thoroughly stirred and uniformly mixed; 2) The mixture was placed in a freeze dryer and freeze-dried at -10 ° C for 30 hours, and then taken out to form solid honey, and the solid honey layer was pulverized into 500-mesh honey powder.
  • the above hydrophobically modified calcium alginate fiber is obtained by the following processing techniques: (1) Hydrophobic modification of alginate: 5 parts by weight of sodium alginate, 0.8 parts by weight of 1-(in terms of important parts) 3-dimethylaminopropyl)-3-ethylcarbodiimide, 0.6 parts by weight of N-hydroxysuccinimide, in order to add 180 parts by weight of a phosphate buffer solution having a pH of 6 in a certain molar ratio After stirring, 60 parts by weight of a methanol solution containing dodecylamine was added, stirred at room temperature for 24 hours, then precipitated with methanol, centrifuged, and the precipitate was dissolved in distilled water, dialyzed for 96 hours, and freeze-dried to obtain hydrophobically modified alginic acid.
  • the antibacterial test of Examples 1 to 4 was carried out by using a common pure alginate functional dressing as a control.
  • the bacteriostatic property of the composite dressing obtained by the present invention is further improved on the basis of the original alginate dressing, and basically reaches 100%.
  • mice Male New Zealand rabbits, 72 rats, each 2 to 3 kg, were randomly divided into six groups of 12 animals each. Each rabbit was treated with a standard burn model of clinical animal burns to cause 30% TBSA shallow second degree burns. Group A rabbits did not use any dressings, and group B rabbits applied common alginate functional dressings, C, D, E, Group F was applied with the composite liquid dressings of Examples 1 to 4 of the present invention, and was changed twice a day until the wounds of the C, D, E, and F groups were healed to end the animal experiment.
  • Group Wound infection rate (%) 7d healing rate (%) Frequent replacement Healing time (d)
  • Group A 100 Redness / After 16 days, the redness and swelling gradually receded and began to scar.
  • Group B 20 Slight redness Need to change twice a day 16.8 ⁇ 1.9
  • Group C 0 73.6 ⁇ 2.5 Change once a day 8.8 ⁇ 1.6
  • Group D 0 71.8 ⁇ 1.4 Change once a day 9.5 ⁇ 2.1
  • Group E 0 69.9 ⁇ 2.0 Change once a day 10.8 ⁇ 1.7
  • Group F 0 72.5 ⁇ 1.8 Change once a day 11.2 ⁇ 2.2
  • the alginate dressing and the dressing prepared by the invention can accelerate the healing of the wound, and the dressings of the C-F group can carry out the full-scale of the wound because of the biological active ingredient.
  • Nursing, and when the dressing frequency is lower (continuous efficacy), can promote wound healing and shorten healing time.

Abstract

本发明公开了一种藻酸盐创面修复敷料及其制备方法，通过将藻酸盐与蜂蜜及45S5生活活性玻璃进行有机结合，充分发挥充分发挥藻酸盐在护理创面时高吸湿性、止血性、柔软成胶性，而且将藻酸盐、蜂蜜、生物活性玻璃三种功能材料在护理创面时表现出的抗菌、止痛、分泌生长因子以促进伤口愈合进行有机结合，从而产生协同的护创作用，使对伤口的护理达到最佳。此外，通过将藻酸盐进行疏水改性后使得生物活性玻璃以及蜂蜜在护创时进行的离子交换得以缓慢进行，使得该敷料能持续发挥护创功效，可减少换药次数，提高患者的舒适度。本发明加工制备的复合材料的制备过程无需特殊设备、反应条件温和、工艺成熟、适合于工业上的规模化生产。

Description

一种藻酸盐创面修复敷料及其制备方法 技术领域
本发明涉及医用耗材技术领域，具体包含一种藻酸盐创面修复敷料及其制备方法。
背景技术
伤口是由机械、电、热、化学等因素造成的或由一种医学或生理变态形成的皮肤缺陷。伤口也可以根据病理学、受伤部位、致伤原因或伤口颜色等条目进行分类。一般来说，根据愈合时间长短，可以分为急性伤口和慢性伤口。伤口愈合是指机体组织遭受创伤后进行再生修复的复杂过程。以皮肤伤口的愈合过程为例，包括伤口早期的炎症反应、伤口收缩、肉芽组织增生和表皮再生等阶段。患者本身的身体素质和伤口护理的情况不同，伤口愈合过程中各阶段的具体表现和持续时间也有所差异，对治疗过程中所使用的敷料也有不同的要求。
随着生活水平的提升，患者对护理伤口敷料的要求越来越高，一些常规的敷料目前难以适用于复杂慢性伤口的护理。因此，寻求一种适合慢性复杂伤口且能持续发挥效果、减少换药次数的敷料，是临床上的迫切需求。
藻酸盐敷料是“伤口湿性愈合理论”下形成的新型敷料之一，主要成份是藻酸钙，是一种不溶于水的物质。当其遇到富含钠离子的液体(如渗液和血液等)时，钙钠离子会发生交换，钙离子被释放出来，而钠离子则与海藻酸结合，形成了亲水的凝胶状物质，帮助伤口维持湿性环境和加强自溶性清创，以及促进肉芽组织的生长。但单一的藻酸盐敷料难以适应慢性复杂伤口的护理要求，因此将其与其他生物医用功能材料进行复合，各取所长，从而达到对伤口护理水平的最佳，是目前开发敷料产品的一种趋势。
发明内容
本发明的目的是为了解决现有藻酸盐敷料在护理慢性复杂伤口方面的不足，而提供一种可镇痛、清创、抑菌、或持续发挥功效并加速伤口愈合的藻酸盐创面修复敷料。
为了实现上述目的，本发明提供的技术方案为：
一种藻酸盐创面修复敷料及其制备方法，其特征在于由海藻酸钙纤维与生物活性粉体复合加工制备得到，所述的生物活性粉体在敷料中的重量百分比为5～20％。
进一步地，所述的海藻酸钙纤维为经疏水改性后的藻酸盐纤维，其加工工艺如下：
1)藻酸盐的疏水改性：按重要份数计，将2～5重量份的海藻酸钠、0.5～1重量份的1-(3-二甲氨基丙基)-3-乙基碳二亚胺、0.5～1重量份的N-羟基琥珀酰亚胺按一定的摩尔比，依次加入到100～200重量份的pH为6～7的磷酸盐缓冲溶液中，搅拌均匀后加入到50～100重量份的含十二胺的甲醇溶液，室温搅拌12～24h,然后用甲醇沉淀，离心分离，沉淀用蒸馏水溶解，透析48～96h，冷冻干燥，即得到疏水改性的海藻酸钠。
2)湿法纺丝：将海藻酸钠完全溶于蒸馏水形成10～15％的藻酸盐溶液(纺丝液)，将纺丝液倒入注射器中，另一端与氮气瓶相连，在氮气压力下挤入5～10％的氯化钙溶液(凝固浴)中，从凝固浴中导出的凝胶状纤维，经拉伸、水洗、卷绕、干燥后得到海藻酸钙纤维。
优选地，所述的生物活性粉体由蜂蜜干粉和生物活性玻璃粉体按1：3～5的重量比均匀拌合而成。
优选地，所述的生物活性玻璃粉体为45S5生物活性玻璃，其粒径小于30μm。
优选地，所述的蜂蜜干粉的制备方法如下：
1)按重量份数计，将50～100份的蜂蜜在65～80℃下解晶液化，然后再进行低温脱水至蜂蜜的水份含量为15～25％，再加入0.5～3份的透皮吸收促进剂使其充分搅拌均匀混合，
2)将上述混合物放入冷冻干燥器内在零下-40～-10℃进行冷冻干燥12～36小时后取出形成固态蜂蜜，再将固态蜂蜜层粉碎成60目～500目的蜂蜜粉；
优选地，所述的透皮吸收促进剂为合成龙脑、聚乙二醇、丙二醇、植物挥发油类花椒油、丁香油当中的任意一种组成。
优选地，所述的敷料制备工艺如下：
1)将生物活性粉加入水和乙醇(体积比为1：1)的混合液中，并使粉体均匀分散形成混悬液；
2)将经疏水改性的海藻酸钙纤维浸入饱和KMnO 4中5～10min，然后用蒸馏水洗净得到去粗的藻酸盐纤维；
3)将上述去粗的藻酸盐纤维浸入混悬液中并充分浸泡，并将混悬液均匀喷涂于纤维表面，然后离心脱水，所得湿纤维在乙醇溶液中浸泡，离心除去乙醇，自然晾干，随后经60～80℃真空干燥；
4)将上述3)中经加工处理的纤维分切成短纤维，经梳理、铺网、针刺工艺制成无纺布，然后将无纺布分切、包装、灭菌后即得藻酸盐创面修复敷料成品。
蜂蜜是一种成分复杂、营养丰富的过饱和糖溶液，具有极高的渗透压和较低的pH值，含有过氧化氢及丙酮醛类等杀菌成分，具有广谱的抗菌活性，且其抗菌活性没有产生耐药性的危险。蜂蜜以其广谱的抗菌活性和不易产生耐药性等优点被广泛用于伤口治疗，不仅可用于局部急性伤口感染的治疗，对难愈创面的治疗更能体现其优势，可通过抗菌、自溶清创和促进组织生长等过程促进伤口愈合。蜂蜜对伤口的作用机理及优点表现在：1)蜂蜜中的过氧化氢作用∶过氧化氢是蜂蜜的主要物质，已被确认为是细菌的“抑制剂”，且蜂蜜稀释所产生的过氧化氢的有害作用被降低，不会损伤人皮肤中的成纤维细胞，因而对伤口愈合无副作用。2)蜂蜜的高渗透性抗菌作用：蜂蜜的抗菌特性是由其高糖成份的渗透性作用所致，且吸收伤口中脓液而起“清创作用”；直接作用于伤口时，在表面形成一层黏性屏障，既避免体液流失，又预防细菌入侵。蜂蜜的酸性抑菌作用:研究发现，天然蜂蜜是酸性的pH3.2-4.5，而引起伤口感染的大多数病原菌生长繁殖的适宜pH为7.0-7.5，因此，低浓度蜂蜜有抑菌作用，高浓度蜂蜜有杀菌作用。
生物活性玻璃作为无机生物合成材料具有独特的表面活性，生物活性玻璃特有的化学组成，特别是其钙、磷等离子沉积生成支架状羟基磷灰石层，从而使其具有巨大的比表面积，利于细胞黏附生长，利于营养和氧气进入，代谢产物排出，也利于血管和神经长入。生物活性玻璃是目前唯一能促进生长因子的生成、促进细胞繁衍、活化细胞基因表达的人工合成的无机材料，还能持续性地诱导细胞本身的上皮生长因子合成，为创面局部提供患者自身的具有完全生物功能的天然上皮生长因子，对创面快速愈合起了重要作用。45S5生物活性玻璃能促进皮肤等软组织的再生，加速促进伤口愈合的机理为：(1)在体液的作用下，首先溶出Na +、Ca 2+等活性大的离子，体液中的H +进入玻璃表面形成Si-OH-；(2)由于Si-O-Si 键破坏，无规网络被溶解，可溶性硅以硅醇形式被放出，并且迅速在材料粉体表面形成一个羟基磷灰石胶结层；(3)可溶性硅有分子水平结缔组织的代谢作用和结构作用，生物玻璃溶解后，局部Si浓度的升高可促进细胞新陈代谢的细胞内部响应，激发促创伤愈合因子的自分泌反应，参与创伤修复的所有细胞在促创伤愈合因子的刺激下加速生长和分裂，并聚集于材料表面形成的羟基磷灰石胶结层，使新生组织能沿整个创面顺利爬移和覆盖。
本发明可产生如下的有益效果：通过一定的技术将藻酸盐与蜂蜜、生物活性玻璃进行有机结合，不仅能充分发挥藻酸盐在护理创面时高吸湿性、止血性、柔软成胶性(不粘连伤口)，而且将藻酸盐、蜂蜜、生物活性玻璃三种功能材料在护理创面时表现出的抗菌、止痛、分泌生长因子以促进伤口愈合进行有机结合，在透皮吸收促进剂的作用下产生协同的护创效果，使对伤口的护理达到最佳。此外，通过将藻酸盐进行疏水改性后使得生物活性玻璃以及蜂蜜在护创时进行的离子交换得以缓慢进行，使得该敷料能持续发挥护创功效，可减少换药次数，提高患者的舒适度。
具体实施方式
下面结合实施例对本发明做进一步描述；以下实施例仅用于更加清楚地说明本发明的目的、技术方案及优点，并不能以此来限制本发明的保护范围。
实施例1：
藻酸盐创面修复敷料，采用如下的制备工艺：
(1)将生物活性粉加入水和乙醇(体积比为1：1)的混合液中，并使粉体均匀分散形成混悬液；
(2)将经疏水改性的海藻酸钙纤维浸入饱和KMnO 4中6min，然后用蒸馏水洗净得到去粗的藻酸盐纤维；
(3)将上述去粗的藻酸盐纤维浸入混悬液中并充分浸泡，并将混悬液均匀喷涂于纤维表面，然后离心脱水，所得湿纤维在乙醇溶液中浸泡，离心除去乙醇，自然晾干，随后经60℃真空干燥，最终得到的生物活性粉体在敷料中的重量百分比含量为10％；
(4)将上述3)中经加工处理的纤维分切成短纤维，经梳理、铺网、针刺 工艺制成无纺布，然后将无纺布分切、包装、灭菌后即得藻酸盐创面修复敷料成品。
上述生物活性粉体由蜂蜜干粉和生物活性玻璃粉体按1：3的重量比均匀拌合而成。其中，生物活性玻璃粉体为45S5生物活性玻璃，其粒径小于30μm。蜂蜜干粉通过如下方法制备得到：1)按重量份数计，将60份的蜂蜜在65℃下解晶液化，然后再进行低温脱水至蜂蜜的水份含量为25％，再加入3份的合成龙脑使其充分搅拌均匀混合；2)将上述混合物放入冷冻干燥器内在零下-20℃进行冷冻干燥24小时后取出形成固态蜂蜜，再将固态蜂蜜层粉碎成100目的蜂蜜粉。
上述疏水改性的海藻酸钙纤维是通过如下的加工工艺得到：(1)藻酸盐的疏水改性：按重要份数计，将2重量份的海藻酸钠、1重量份的1-(3-二甲氨基丙基)-3-乙基碳二亚胺、0.5重量份的N-羟基琥珀酰亚胺按一定的摩尔比，依次加入到100重量份的pH为6的磷酸盐缓冲溶液中，搅拌均匀后加入到100重量份的含十二胺的甲醇溶液，室温搅拌18h,然后用甲醇沉淀，离心分离，沉淀用蒸馏水溶解，透析84h，冷冻干燥，即得到疏水改性的海藻酸钠。(2)湿法纺丝：将海藻酸钠完全溶于蒸馏水形成10％的藻酸盐溶液(纺丝液)，将纺丝液倒入注射器中，另一端与氮气瓶相连，在氮气压力下挤入10％的氯化钙溶液(凝固浴)中，从凝固浴中导出的凝胶状纤维，经拉伸、水洗、卷绕、干燥后得到海藻酸钙纤维。
实施例2：
藻酸盐创面修复敷料，采用如下的制备工艺：
(1)将生物活性粉加入水和乙醇(体积比为1：1)的混合液中，并使粉体均匀分散形成混悬液；
(2)将经疏水改性的海藻酸钙纤维浸入饱和KMnO 4中5min，然后用蒸馏水洗净得到去粗的藻酸盐纤维；
(3)将上述去粗的藻酸盐纤维浸入混悬液中并充分浸泡，并将混悬液均匀喷涂于纤维表面，然后离心脱水，所得湿纤维在乙醇溶液中浸泡，离心除去乙醇，自然晾干，随后经80℃真空干燥，最终得到的生物活性粉体在敷料中的重量百分比含量为15％；
(4)将上述3)中经加工处理的纤维分切成短纤维，经梳理、铺网、针刺工艺制成无纺布，然后将无纺布分切、包装、灭菌后即得藻酸盐创面修复敷料成品。
上述生物活性粉体由蜂蜜干粉和生物活性玻璃粉体按1：4的重量比均匀拌合而成。其中，生物活性玻璃粉体为45S5生物活性玻璃，其粒径小于30μm。蜂蜜干粉通过如下方法制备得到：1)按重量份数计，将50份的蜂蜜在70℃下解晶液化，然后再进行低温脱水至蜂蜜的水份含量为15％，再加入2份的聚乙二醇使其充分搅拌均匀混合；2)将上述混合物放入冷冻干燥器内在零下-40℃进行冷冻干燥12小时后取出形成固态蜂蜜，再将固态蜂蜜层粉碎成60目的蜂蜜粉。
上述疏水改性的海藻酸钙纤维是通过如下的加工工艺得到：(1)藻酸盐的疏水改性：按重要份数计，将3重量份的海藻酸钠、0.5重量份的1-(3-二甲氨基丙基)-3-乙基碳二亚胺、1重量份的N-羟基琥珀酰亚胺按一定的摩尔比，依次加入到150重量份的pH为7的磷酸盐缓冲溶液中，搅拌均匀后加入到80重量份的含十二胺的甲醇溶液，室温搅拌12h,然后用甲醇沉淀，离心分离，沉淀用蒸馏水溶解，透析48h，冷冻干燥，即得到疏水改性的海藻酸钠。(2)湿法纺丝：将海藻酸钠完全溶于蒸馏水形成14％的藻酸盐溶液(纺丝液)，将纺丝液倒入注射器中，另一端与氮气瓶相连，在氮气压力下挤入8％的氯化钙溶液(凝固浴)中，从凝固浴中导出的凝胶状纤维，经拉伸、水洗、卷绕、干燥后得到海藻酸钙纤维。
实施例3：
藻酸盐创面修复敷料，采用如下的制备工艺：
(1)将生物活性粉加入水和乙醇(体积比为1：1)的混合液中，并使粉体均匀分散形成混悬液；
(2)将经疏水改性的海藻酸钙纤维浸入饱和KMnO 4中8min，然后用蒸馏水洗净得到去粗的藻酸盐纤维；
(3)将上述去粗的藻酸盐纤维浸入混悬液中并充分浸泡，并将混悬液均匀喷涂于纤维表面，然后离心脱水，所得湿纤维在乙醇溶液中浸泡，离心除去乙醇，自然晾干，随后经70℃真空干燥，最终得到的生物活性粉体在敷料中的重量百 分比含量为5％；
(4)将上述3)中经加工处理的纤维分切成短纤维，经梳理、铺网、针刺工艺制成无纺布，然后将无纺布分切、包装、灭菌后即得藻酸盐创面修复敷料成品。
上述生物活性粉体由蜂蜜干粉和生物活性玻璃粉体按1：5的重量比均匀拌合而成。其中，生物活性玻璃粉体为45S5生物活性玻璃，其粒径小于30μm。蜂蜜干粉通过如下方法制备得到：1)按重量份数计，将100份的蜂蜜在75℃下解晶液化，然后再进行低温脱水至蜂蜜的水份含量为20％，再加入1份的植物挥发油类花椒油使其充分搅拌均匀混合；2)将上述混合物放入冷冻干燥器内在零下-30℃进行冷冻干燥36小时后取出形成固态蜂蜜，再将固态蜂蜜层粉碎成300目的蜂蜜粉。
上述疏水改性的海藻酸钙纤维是通过如下的加工工艺得到：(1)藻酸盐的疏水改性：按重要份数计，将4重量份的海藻酸钠、0.6重量份的1-(3-二甲氨基丙基)-3-乙基碳二亚胺、0.8重量份的N-羟基琥珀酰亚胺按一定的摩尔比，依次加入到200重量份的pH为6.5的磷酸盐缓冲溶液中，搅拌均匀后加入到50重量份的含十二胺的甲醇溶液，室温搅拌16h,然后用甲醇沉淀，离心分离，沉淀用蒸馏水溶解，透析72h，冷冻干燥，即得到疏水改性的海藻酸钠。(2)湿法纺丝：将海藻酸钠完全溶于蒸馏水形成12％的藻酸盐溶液(纺丝液)，将纺丝液倒入注射器中，另一端与氮气瓶相连，在氮气压力下挤入5％的氯化钙溶液(凝固浴)中，从凝固浴中导出的凝胶状纤维，经拉伸、水洗、卷绕、干燥后得到海藻酸钙纤维。
实施例4：
藻酸盐创面修复敷料，采用如下的制备工艺：
(1)将生物活性粉加入水和乙醇(体积比为1：1)的混合液中，并使粉体均匀分散形成混悬液；
(2)将经疏水改性的海藻酸钙纤维浸入饱和KMnO 4中10min，然后用蒸馏水洗净得到去粗的藻酸盐纤维；
(3)将上述去粗的藻酸盐纤维浸入混悬液中并充分浸泡，并将混悬液均匀 喷涂于纤维表面，然后离心脱水，所得湿纤维在乙醇溶液中浸泡，离心除去乙醇，自然晾干，随后经75℃真空干燥，最终得到的生物活性粉体在敷料中的重量百分比含量为20％；
(4)将上述3)中经加工处理的纤维分切成短纤维，经梳理、铺网、针刺工艺制成无纺布，然后将无纺布分切、包装、灭菌后即得藻酸盐创面修复敷料成品。
上述生物活性粉体由蜂蜜干粉和生物活性玻璃粉体按1：4的重量比均匀拌合而成。其中，生物活性玻璃粉体为45S5生物活性玻璃，其粒径小于30μm。蜂蜜干粉通过如下方法制备得到：1)按重量份数计，将80份的蜂蜜在80℃下解晶液化，然后再进行低温脱水至蜂蜜的水份含量为18％，再加入0.5份的丁香油使其充分搅拌均匀混合；2)将上述混合物放入冷冻干燥器内在零下-10℃进行冷冻干燥30小时后取出形成固态蜂蜜，再将固态蜂蜜层粉碎成500目的蜂蜜粉。
上述疏水改性的海藻酸钙纤维是通过如下的加工工艺得到：(1)藻酸盐的疏水改性：按重要份数计，将5重量份的海藻酸钠、0.8重量份的1-(3-二甲氨基丙基)-3-乙基碳二亚胺、0.6重量份的N-羟基琥珀酰亚胺按一定的摩尔比，依次加入到180重量份的pH为6的磷酸盐缓冲溶液中，搅拌均匀后加入到60重量份的含十二胺的甲醇溶液，室温搅拌24h,然后用甲醇沉淀，离心分离，沉淀用蒸馏水溶解，透析96h，冷冻干燥，即得到疏水改性的海藻酸钠。(2)湿法纺丝：将海藻酸钠完全溶于蒸馏水形成15％的藻酸盐溶液(纺丝液)，将纺丝液倒入注射器中，另一端与氮气瓶相连，在氮气压力下挤入6％的氯化钙溶液(凝固浴)中，从凝固浴中导出的凝胶状纤维，经拉伸、水洗、卷绕、干燥后得到海藻酸钙纤维。
实验例5：抑菌性试验
以普通的纯藻酸盐功能性敷料为对照，对实施例1～4进行抗菌性试验，具体方法如下：将以上试样称取5g，洗涤至中性置于三角瓶中，然后分别加入10ml1/10AATCC营养肉汤(或：改良马丁培养基)和10ml缓冲生理盐水(pH＝7.0～7.2)，在高压蒸汽灭菌器中灭菌后冷却至室温，依次接入大肠杆菌、金黄色葡萄球菌及白色念珠菌菌种，置于37℃恒温摇床振荡，一定时间后取溶液0.1ml涂于营养琼脂培养基上(或：沙氏琼脂培养基)，在37℃的恒温箱中培养24h，进行活菌计数。以相同工艺制备的纯硅凝胶为对照样，不加任何试样的菌液 为空白对照，每次抗菌试验均同时进行对照样(普通壳聚糖凝胶)试验和空白对照试验。试验结果如下表1所示：
表1复合凝胶的抑菌试验
Figure PCTCN2018098243-appb-000001
从上表中可以看出，本发明得到的复合敷料与普通藻酸盐敷料相比，其抑菌性在原有的基础上得到更进一步的提升，基本达到100％。
实施例6动物试验
取雄性新西兰兔，72只，每只2～3kg，随机分为六组，每组12只。各兔子均按照临床动物实验烧伤标准模型制备方法均造成30％TBSA浅II度烧伤，其中A组兔子不使用任何敷料，B组兔子敷用普通藻酸盐功能性敷料，C、D、E、F组敷用本发明实施例1～4的复合液体敷料，每天更换两次，直到C、D、E、F组的创面愈合便结束本次动物实验。
从动物实验的结果上看，C～F组兔子创面敷用各自的敷料后，创面均无感染现象、无红肿发生。而从愈合时间上看，C～F组兔子创面的愈合时间明显少于B组，时间差异具有显著意义，见表2：
表2各组动物创面感染及愈合情况(％)
组别 创面感染率(％) 7d愈合率(％) 更换频繁 愈合时间(d)
A组 100 红肿 / 16d后红肿渐退，开始结痂
B组 20 轻微红肿 1天需换两次 16.8±1.9
C组 0 73.6±2.5 1天换一次 8.8±1.6
D组 0 71.8±1.4 1天换一次 9.5±2.1
E组 0 69.9±2.0 1天换一次 10.8±1.7
F组 0 72.5±1.8 1天换一次 11.2±2.2
从六组实验的整体结果上看，藻酸盐敷料和本发明制备的敷料对创面的愈合能起到加速的作用，而C～F组敷料因为含生物活性成分，可对创面进行全方位的护理，且换药频率更低时(持续疗效)，能促进创面愈合并缩短愈合时间。

Claims (7)

  1. 一种藻酸盐创面修复敷料，其特征在于，由海藻酸钙纤维与生物活性粉体复合加工制备得到，所述的生物活性粉体在敷料中的重量百分比为5～20％。
  2. 根据权利要求1所述的一种藻酸盐创面修复敷料，其特征在于，所述的海藻酸钙纤维为经疏水改性的藻酸盐纤维，其加工工艺如下：
    1)藻酸盐的疏水改性：按重要份数计，将2～5重量份的海藻酸钠、0.5～1重量份的1-(3-二甲氨基丙基)-3-乙基碳二亚胺、0.5～1重量份的N-羟基琥珀酰亚胺按一定的摩尔比，依次加入到100～200重量份的pH为6～7的磷酸盐缓冲溶液中，搅拌均匀后加入到50～100重量份的含十二胺的甲醇溶液，室温搅拌12～24h,然后用甲醇沉淀，离心分离，沉淀用蒸馏水溶解，透析48～96h，冷冻干燥，即得到疏水改性的海藻酸钠。
    2)湿法纺丝：将疏水改性的海藻酸钠完全溶于蒸馏水形成10～15％的藻酸盐溶液(纺丝液)，将纺丝液倒入注射器中，另一端与氮气瓶相连，在氮气压力下挤入5～10％的氯化钙溶液(凝固浴)中，从凝固浴中导出的凝胶状纤维，经拉伸、水洗、卷绕、干燥后得到海藻酸钙纤维。
  3. 根据权利要求1所述的一种藻酸盐创面修复敷料，其特征在于，所述的生物活性粉体由蜂蜜干粉和生物活性玻璃粉体按1：3～5的重量比均匀拌合而成。
  4. 根据权利要求3所述的一种藻酸盐创面修复敷料，其特征在于，所述的生物活性玻璃粉体为45S5生物活性玻璃，其粒径小于30μm。
  5. 根据权利要求3所述的一种藻酸盐创面修复敷料，其特征在于，所述的蜂蜜干粉的制备方法如下：
    1)按重量份数计，将50～100份的蜂蜜在65～80℃下解晶液化，然后再进行低温脱水至蜂蜜的水份含量为15～25％，再加入0.5～3份的透皮吸收促进剂使其充分搅拌均匀混合；
    2)将上述混合物放入冷冻干燥器内在零下-40～-10℃进行冷冻干燥12～36小时后取出形成固态蜂蜜，再将固态蜂蜜层粉碎成60目～500目的蜂蜜粉；
  6. 根据权利利要求5所述的一种藻酸盐创面修复敷料，其特征在于，所述的透皮吸收促进剂为合成龙脑、聚乙二醇、丙二醇、植物挥发油类花椒油、丁香油当中的任意一种组成。
  7. 权利要求1所述的一种藻酸盐创面修复敷料的制备方法，其特征在于，包括如下步骤：
    1)将生物活性粉加入水和乙醇(体积比为1：1)的混合液中，并使粉体均匀分散形成混悬液；
    2)将经疏水改性的海藻酸钙纤维浸入饱和KMnO 4中5～10min，然后用蒸馏水洗净得到去粗的藻酸盐纤维；
    3)将上述去粗的藻酸盐纤维浸入混悬液中并充分浸泡，并将混悬液均匀喷涂于纤维表面，然后离心脱水，所得湿纤维在乙醇溶液中浸泡，离心除去乙醇，自然晾干，随后经60～80℃真空干燥；
    4)将上述3)中经加工处理的纤维分切成短纤维，经梳理、铺网、针刺工艺制成无纺布，然后将无纺布分切、包装、灭菌后即得藻酸盐创面修复敷料成品。
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