WO2018129761A1 - 聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜及其制备方法、应用 - Google Patents

聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜及其制备方法、应用 Download PDF

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WO2018129761A1
WO2018129761A1 PCT/CN2017/071507 CN2017071507W WO2018129761A1 WO 2018129761 A1 WO2018129761 A1 WO 2018129761A1 CN 2017071507 W CN2017071507 W CN 2017071507W WO 2018129761 A1 WO2018129761 A1 WO 2018129761A1
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hydroxyapatite
sodium alginate
polyvinyl alcohol
solution
fiber membrane
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PCT/CN2017/071507
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English (en)
French (fr)
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韩颖超
赵刚
戴红莲
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武汉理工大学
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Priority to US16/067,820 priority Critical patent/US11786629B2/en
Publication of WO2018129761A1 publication Critical patent/WO2018129761A1/zh

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    • D—TEXTILES; PAPER
    • D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/40—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties
    • D04H1/42—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties characterised by the use of certain kinds of fibres insofar as this use has no preponderant influence on the consolidation of the fleece
    • D04H1/4282—Addition polymers
    • D04H1/4309—Polyvinyl alcohol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/00987—Apparatus or processes for manufacturing non-adhesive dressings or bandages
    • 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
    • A61L15/225—Mixtures of macromolecular compounds
    • 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
    • A61L15/44—Medicaments
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L29/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers
    • C08L29/02—Homopolymers or copolymers of unsaturated alcohols
    • C08L29/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/04—Alginic acid; Derivatives thereof
    • 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
    • D01D1/00—Treatment of filament-forming or like material
    • D01D1/02—Preparation of spinning solutions
    • D—TEXTILES; PAPER
    • D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/40—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties
    • D04H1/42—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres from fleeces or layers composed of fibres without existing or potential cohesive properties characterised by the use of certain kinds of fibres insofar as this use has no preponderant influence on the consolidation of the fleece
    • D04H1/4382—Stretched reticular film fibres; Composite fibres; Mixed fibres; Ultrafine fibres; Fibres for artificial leather
    • D04H1/43825—Composite fibres
    • D—TEXTILES; PAPER
    • D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
    • D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
    • D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/70—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
    • D04H1/72—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
    • D04H1/728—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
    • 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
    • A61L2300/406—Antibiotics
    • 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
    • A61L2300/414—Growth factors
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/34—Materials or treatment for tissue regeneration for soft tissue reconstruction
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/32—Phosphorus-containing compounds
    • C08K2003/321—Phosphates
    • C08K2003/325—Calcium, strontium or barium phosphate

Definitions

  • the invention relates to the technical field of electrospinning, in particular to a polyvinyl alcohol/sodium alginate/hydroxyapatite composite fiber membrane and a preparation method and application thereof.
  • Soft tissue damage is now a very common type of lesion.
  • Soft tissue is often referred to as the skin, subcutaneous tissue, muscles, tendons, ligaments, joint capsules, synovial sacs, nerves, blood vessels, etc. of the human body.
  • skin can protect various tissues and organs in the body from external mechanical and pathogenic damage, and skin damage and defects can cause a series of physiological and pathological problems.
  • artificial medical dressing can also protect damaged skin, provide a good physiological repair environment for wound healing, and there is no problem of limited source of autologous skin, and has broad application prospects.
  • the ideal artificial medical dressing is not only to cover the wound, but also must meet the following conditions: non-toxic, good biocompatibility, easy to use and no need to change frequently, can prevent bacterial invasion, remove exudate and keep the wound moist. Has a certain biological activity to promote wound repair.
  • the material of the artificial medical dressing we divide it into traditional dressings, natural dressings, synthetic dressings and medicinal dressings. Combining the advantages and disadvantages of these dressings, using the electrospinning method to combine the excellent properties of natural polymers and synthetic polymer materials, to prepare biocompatible and bioactive composite fiber membranes and use them as soft tissue damage repair dressings. It is an urgent need of people today.
  • Electrospinning technology originated in the 1930s and has flourished in the last 20 years.
  • the technology is low in manufacturing cost, simple in process, and can quickly obtain a wide variety of ultrafine fibers with a fiber diameter distribution ranging from a few nanometers to several micrometers, and is thus recognized as one of the most important methods for mass-producing nanofiber materials.
  • the electrospun nanofiber material with three-dimensional spatial structure not only has the characteristics of small size and large specific surface area, but also has the advantages of good mechanical stability, small pore diameter of the fiber membrane, high porosity and good fiber continuity. It facilitates the adhesion, migration and proliferation of cells, thereby replicating the three-dimensional tissue structure to be replaced, and enabling cells to differentiate and grow in cell lines in different directions.
  • Sodium alginate is a safe and non-toxic natural polymer material with high hygroscopicity, hemostasis, gelation, promotion of wound healing, bacteriostasis, reduction of local pain, reduction of scar formation, etc. A good micro environment.
  • polyvinyl alcohol is due to its outstanding film formability and filamentity.
  • Hydroxyapatite is a highly biocompatible and biologically active inorganic material. It is an inorganic component in human bones. It has high cell adhesion, high cell affinity, and calcium and phosphate ions produced by degradation. Provides nutrients for cell growth.
  • sodium alginate itself is a polyelectrolyte.
  • the invention realizes the uniform dispersion of the hydroxyapatite nanoparticles in the composite fiber membrane, and the prepared composite fiber membrane combines the biocompatibility of the natural polymer, the synthetic polymer and the biological activity of the hydroxyapatite nanoparticles, Used as a soft tissue injury repair dressing, and can be loaded with antibiotics or growth factors to improve the repair of soft tissue damage.
  • the object of the present invention is to solve the problems that the composite fiber membrane dressing has insufficient comprehensive performance, the hydroxyapatite nanoparticles of the spinning raw material are easily agglomerated, and the dispersion is uneven, and the like, and a polyvinyl alcohol/sodium alginate/hydroxyphosphorus is provided.
  • the composite fiber membrane combines the biocompatibility of natural polymers and synthetic polymers with the biological activity of hydroxyapatite nanoparticles, and is an excellent soft tissue damage repair dressing, and can itself be loaded with antibiotics or growth factors. Soft tissue damage repair effect.
  • the technical solution adopted by the present invention is as follows:
  • a polyvinyl alcohol/sodium alginate/hydroxyapatite composite fiber membrane wherein the mass ratio of polyvinyl alcohol, sodium alginate and hydroxyapatite is 1:0.01-0.0563:0.01-0.0834.
  • the preparation method of the above polyvinyl alcohol/sodium alginate/hydroxyapatite composite fiber membrane comprises the following steps: (a) preparing hydroxyapatite by reacting diammonium phosphate and calcium nitrate, and dispersing the hydroxyapatite In the ionic water, sodium alginate is added and uniformly mixed to obtain a suspension of hydroxyapatite stabilized by sodium alginate; (b) the suspension of hydroxyapatite stabilized by sodium alginate prepared by the step (a) respectively Preparing a sodium alginate solution containing hydroxyapatite and a polyvinyl alcohol solution containing hydroxyapatite; (c) the above sodium alginate solution containing hydroxyapatite and a polyvinyl alcohol solution containing hydroxyapatite
  • the spinning solution containing hydroxyapatite, sodium alginate and polyvinyl alcohol was uniformly mixed in proportion, and electrospinning was carried out by using a spinning solution to obtain
  • the concentration of the aqueous solution of diammonium hydrogen phosphate is 0.001-0.1 mol/L, and the concentration of the aqueous solution of calcium nitrate is 0.00668-0.167 mol/L.
  • the hydroxyapatite suspension is prepared by ultrasonication, and the concentration of sodium alginate in the suspension is 0.04-0.15 mg/mL, and the concentration of hydroxyapatite is 1.67-16.7 mg/mL.
  • a sodium alginate solution having a mass fraction of 2% and a polyvinyl alcohol solution having a mass fraction of 18% were prepared at 60-80 °C.
  • the volume ratio of the sodium alginate solution containing hydroxyapatite and the polyvinyl alcohol solution containing hydroxyapatite is 0.1 to 1:1-2.
  • the electrospinning voltage is 10-15 kV
  • the receiving distance is 13-18 cm
  • the advancing speed is 0.03-0.05 mm/min.
  • an antibiotic or a growth factor equivalent to 1-5 wt% of the total mass of polyvinyl alcohol, sodium alginate and hydroxyapatite is added to the spinning solution.
  • the above polyvinyl alcohol/sodium alginate/hydroxyapatite composite fiber membrane is used as a soft tissue damage repair dressing.
  • the invention has the beneficial effects that the hydroxyapatite is stably and uniformly dispersed in water by using sodium alginate combined with ultrasonic method without introducing other impurities, thereby solving the problem of easy agglomeration of hydroxyapatite.
  • the problem of using the electrospinning method, organically and inorganic nanocomposite technology organically combines the excellent properties of natural polymers and synthetic polymer materials to prepare biopolymers with natural polymers, synthetic polymers, and hydroxyphosphorus.
  • Gray fiber nano-particle bioactive composite fiber membrane which can be used as a repair dressing for soft tissue damage, and can be loaded with antibiotics or growth factors to improve the repair effect of soft tissue damage.
  • Example 1 is a photograph showing the sedimentation of a hydroxyapatite suspension stabilized with sodium alginate and an untreated hydroxyapatite dispersion over time in Example 1 of the present invention
  • Example 2 is a graph showing the change of light transmittance of a hydroxyapatite suspension and an untreated hydroxyapatite dispersion with time after stabilization by sodium alginate in Example 1 of the present invention
  • Example 3 is a particle size diagram of a hydroxyapatite suspension stabilized by sodium alginate in Example 1 of the present invention
  • Example 4 is a scanning electron micrograph of a composite fiber membrane prepared in Example 2 of the present invention.
  • Figure 5 is a scanning electron micrograph of a composite fiber membrane prepared in Example 3 of the present invention.
  • Figure 6 is a photomicrograph of a composite fiber membrane prepared in Example 4 of the present invention.
  • Figure 7 is a fluorescence micrograph of a composite fiber membrane prepared in Example 4 of the present invention.
  • the invention provides a polyvinyl alcohol/sodium alginate/hydroxyapatite composite fiber membrane and a preparation method thereof, as follows:
  • the white precipitate of hydroxyapatite is dispersed in deionized water, and then sodium alginate is ultrasonically mixed and dispersed to obtain a suspension of hydroxyapatite stabilized by sodium alginate, wherein the concentration of sodium alginate is 0.04-0.15 mg/mL.
  • the concentration of hydroxyapatite is 1.67-16.7 mg/mL.
  • the second step is to prepare a sodium alginate solution having a mass fraction of 2% and a polyvinyl alcohol solution having a mass fraction of 18% by using the aforementioned suspension of hydroxyapatite stabilized by sodium alginate at 60-80 ° C, respectively.
  • the concentration of hydroxyapatite contained in the two solutions is 1.67-16.7 mg/mL
  • the prepared sodium alginate solution containing hydroxyapatite and the polyvinyl alcohol solution containing hydroxyapatite are uniformly mixed in a volume ratio of 0.1-1:1-2 to obtain hydroxyapatite, sodium alginate and
  • the spinning solution of polyvinyl alcohol is electrospun by the spinning solution to obtain a composite fiber membrane, wherein the electrospinning process parameters are: voltage 10-15 kv, receiving distance 13-18 cm, and advancing speed 0.03-0.05 mm/min.
  • the mass ratio of polyvinyl alcohol, sodium alginate and hydroxyapatite in the composite fiber membrane prepared according to the method of the invention is 1:0.01-0.0563:0.01-0.0834.
  • the composite fiber membrane can be used as a soft tissue damage repair dressing, and adding antibiotics or growth factors to the spinning solution can also improve the repair effect of soft tissue damage.
  • an aqueous calcium nitrate solution having a concentration of 0.0334 mol/L and an aqueous solution of diammonium hydrogen phosphate having a concentration of 0.02 mol/L were separately prepared.
  • the white precipitate was redispersed in 40 mL of deionized water to obtain a hydroxyapatite dispersion having a concentration of 1.67 mg/mL, and 20 mL of this dispersion was taken. 10 mL of deionized water and 0.1 g of sodium alginate were used to prepare a sodium alginate solution with a mass fraction of 1%, and 0.08 mL of sodium alginate solution was added to the above 20 mL of the dispersion, and the mixture was uniformly mixed for 30 seconds to obtain stable sodium alginate. After the hydroxyapatite suspension.
  • step 2) Take two 10 mL of the hydroxyapatite suspension obtained in the step 1), add 0.2 g of sodium alginate and 1.8 g of polyvinyl alcohol, respectively, and dissolve at 80 ° C to obtain sodium alginate (SA) having a mass fraction of 2%. A solution and a mass fraction of 18% polyvinyl alcohol (PVA) solution, and the two solutions contained a hydroxyapatite concentration of 1.67 mg/mL.
  • SA sodium alginate
  • PVA polyvinyl alcohol
  • the sedimentation photograph of the hydroxyapatite suspension stabilized by sodium alginate and the untreated hydroxyapatite dispersion in the step (1) of the present embodiment is shown in Fig. 1, wherein the left side is alginic acid.
  • the hydroxyapatite suspension after sodium stabilization, the untreated hydroxyapatite dispersion on the right, a, b, c, d, e represent photos after standing for 0h, 1h, 2h, 5h, 24h. It can be clearly seen from the comparison that the untreated hydroxyapatite dispersion has a significant sedimentation in a short period of time due to the particularly easy agglomeration of hydroxyapatite, and is stabilized by sodium alginate. The subsequent hydroxyapatite suspension can remain stable for a longer period of time.
  • the relationship between the transmittance of the hydroxyapatite suspension stabilized by sodium alginate and the untreated hydroxyapatite dispersion in the step (1) of the present embodiment is as shown in FIG. 2, It can be clearly seen in the figure that the untreated hydroxyapatite dispersion (curve a) is unstable due to the instability of the solution caused by the agglomeration of the particles, resulting in a stable change with sodium alginate. The latter hydroxyapatite suspension is much more stable than the untreated hydroxyapatite dispersion.
  • the average particle diameter of the hydroxyapatite obtained is 148 nm, which also indicates the hydroxyl group.
  • the apatite is well dispersed.
  • an aqueous calcium nitrate solution having a concentration of 0.0334 mol/L and an aqueous solution of diammonium hydrogen phosphate having a concentration of 0.02 mol/L were separately prepared.
  • the white precipitate was redispersed in 40 mL of deionized water to obtain a hydroxyapatite dispersion having a concentration of 1.67 mg/mL, and 20 mL of this dispersion was taken. 10 mL of deionized water and 0.1 g of sodium alginate were used to prepare a sodium alginate solution with a mass fraction of 1%, and 0.08 mL of sodium alginate solution was added to the above 20 mL of the dispersion, and the mixture was uniformly mixed for 30 seconds to obtain stable sodium alginate. After the hydroxyapatite suspension.
  • step 2) Take two 10 mL of the hydroxyapatite suspension obtained in the step 1), add 0.2 g of sodium alginate and 1.8 g of polyvinyl alcohol, respectively, and dissolve at 80 ° C to obtain sodium alginate (SA) having a mass fraction of 2%. A solution and a mass fraction of 18% polyvinyl alcohol (PVA) solution, and the two solutions contained a hydroxyapatite concentration of 1.67 mg/mL.
  • SA sodium alginate
  • PVA polyvinyl alcohol
  • an aqueous calcium nitrate solution having a concentration of 0.0334 mol/L and an aqueous solution of diammonium hydrogen phosphate having a concentration of 0.02 mol/L were separately prepared.
  • the white precipitate was redispersed in 20 mL of deionized water to give a hydroxyapatite dispersion at a concentration of 10.02 mg/mL, ready for use. Take 10 mL of deionized water and 0.1 g of sodium alginate to prepare a sodium alginate solution with a mass fraction of 1%, add 0.2 mL of sodium alginate solution to the above 20 mL of the dispersion, and mix well for 30 s to obtain stable sodium alginate. After the hydroxyapatite suspension.
  • step 2) Take two 10 mL of the hydroxyapatite suspension obtained in the step 1), add 0.2 g of sodium alginate and 1.8 g of polyvinyl alcohol, respectively, and dissolve at 80 ° C to obtain sodium alginate (SA) having a mass fraction of 2%. A solution and a mass fraction of 18% polyvinyl alcohol (PVA) solution, and the two solutions contained a hydroxyapatite concentration of 10.02 mg/mL.
  • SA sodium alginate
  • PVA polyvinyl alcohol
  • the scanning electron microscopy of the polyvinyl alcohol/sodium alginate/hydroxyapatite composite fiber membrane prepared in this example is shown in Fig. 5. It can be seen from the picture that the composite fiber has a good morphology.
  • an aqueous calcium nitrate solution having a concentration of 0.0334 mol/L and an aqueous solution of diammonium hydrogen phosphate having a concentration of 0.02 mol/L were separately prepared.
  • the white precipitate was redispersed in 40 mL of deionized water to obtain a hydroxyapatite dispersion having a concentration of 1.67 mg/mL, and 20 mL of this dispersion was taken. 10 mL of deionized water and 0.1 g of sodium alginate were used to prepare a sodium alginate solution with a mass fraction of 1%, and 0.08 mL of sodium alginate solution was added to the above 20 mL of the dispersion, and the mixture was uniformly mixed for 30 seconds to obtain stable sodium alginate. After the hydroxyapatite suspension.
  • step 2) Take two 10 mL of the hydroxyapatite suspension obtained in the step 1), add 0.2 g of sodium alginate and 1.8 g of polyvinyl alcohol, respectively, and dissolve at 80 ° C to obtain sodium alginate (SA) having a mass fraction of 2%. A solution and a mass fraction of 18% polyvinyl alcohol (PVA) solution, and the two solutions contained a hydroxyapatite concentration of 1.67 mg/mL.
  • SA sodium alginate
  • PVA polyvinyl alcohol
  • the optical microscope and fluorescence microscope of the polyvinyl alcohol/sodium alginate/hydroxyapatite composite fiber membrane prepared in this example are shown in Fig. 6-7. It can be seen from the optical microscope of the composite fiber membrane that the morphology of the fiber is good. The fluorescence of the composite fiber membrane shows the characteristic fluorescence of tetracycline hydrochloride, indicating that it has been successfully loaded into the composite fiber membrane.

Abstract

一种聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜及其制备方法和应用。该复合纤维膜制备方法包括：首先采用磷酸氢二铵和硝酸钙反应制备羟基磷灰石，将羟基磷灰石和海藻酸钠超声分散成稳定的羟基磷灰石悬浮液；接着用此悬浮液分别配制质量分数为2%的海藻酸钠溶液和18%的聚乙烯醇溶液；最后将两种溶液按比例混合均匀进行静电纺丝。

Description

[根据细则37.2由ISA制定的发明名称]　聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜及其制备方法、应用 技术领域
本发明涉及静电纺丝技术领域，具体涉及一种聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜及其制备方法和应用。
背景技术
软组织的损伤是现在非常普遍的一种病损。人们常说的软组织是指人体的皮肤、皮下组织、肌肉、肌腱、韧带、关节囊、滑膜囊，神经、血管等。以皮肤为例，它可以保护体内各种组织和器官免受外来机械性和病原性的侵害，皮肤损伤、缺损会导致一系列生理病理的问题。针对大面积的皮肤缺损，除了自体皮肤移植修复，人工医用敷料也可保护受损皮肤，为伤口愈合提供良好的生理修复环境，且不存在自体皮肤来源有限的问题，具有广泛的应用前景。
理想的人工医用敷料不仅是为了覆盖创面，还必须满足以下条件：无毒，有很好的生物相容性，方便使用且无须经常更换，可阻碍细菌入侵，可除去渗液并保持伤口湿润，具有一定生物活性可促进创面修复。一般我们根据人工医用敷料的材质，将其分成传统类敷料、天然类敷料、合成类敷料和药用性敷料。综合这些敷料的优缺点，使用静电纺丝法有机的结合天然高分子与合成高分子材料的优良特性，制备出具有生物相容性和生物活性的复合纤维膜并将其用作软组织损伤修复敷料，是人们当前的一种迫切需求。
静电纺丝技术起源于20世纪30年代，并在近20年的时间里得到了蓬勃的发展。该技术制造成本低廉、工艺简单，可快速获得纤维直径分布从几纳米到几微米且品种繁多的超细纤维，因而被公认为是最具有批量制造纳米纤维材料潜力的重要方法之一。具有三维立体空间结构的静电纺丝纳米纤维材料，不但具备纳米颗粒尺寸微小、比表面积大等特性，同时它还有力学稳定性好、纤维膜孔径小、孔隙率高、纤维连续性好等优点，便于细胞的黏附、迁移以及增殖，进而复制要替换的三维组织结构，并能使细胞沿着不同方向的细胞系分化生长。
海藻酸钠是一种安全无毒性的天然高分子材料，具有高吸湿性、止血性、成胶性、促进伤口愈合、抑菌性、减少局部疼痛、减少疤痕形成等优点，为损伤皮肤修复提供了良好的微环境。聚乙烯醇作为具有很好生物相容性的合成高分子，由于其突出的成膜性和成丝性，是 静电纺丝的常用原料。羟基磷灰石是一种高生物相容性和生物活性的无机材料，是人体骨骼中的无机成份，具有高细胞粘附性、高细胞亲和性，并且降解产生的钙离子、磷酸根离子可为细胞生长提供养分。但海藻酸钠本身是聚电解质，单一组分的海藻酸钠很难利用静电纺丝法得到纤维膜，且降解后会引起微环境呈弱酸性，而羟基磷灰石本身呈弱碱性。故考虑将以上三种材料混合纺丝达到优势互补的目的。
本发明实现了羟基磷灰石纳米粒子在复合纤维膜中的均匀分散，制备的复合纤维膜结合了天然高分子、合成高分子的生物相容性以及羟基磷灰石纳米粒子的生物活性，可用作软组织损伤修复敷料，并可装载抗生素或生长因子提高软组织损伤修复效果。
发明内容
本发明的目的在于解决现有复合纤维膜敷料综合性能不够优异，纺丝原料羟基磷灰石纳米粒子极易团聚、容易分散不均匀等问题，提供一种聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜及其制备方法。该复合纤维膜综合了天然高分子、合成高分子的生物相容性以及羟基磷灰石纳米粒子的生物活性，是一种优良的软组织损伤修复敷料，并且其本身还可装载抗生素或生长因子提高软组织损伤修复效果。为实现上述目的，本发明所采用的技术方案如下：
一种聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜，其中聚乙烯醇、海藻酸钠、羟基磷灰石的质量比为1:0.01-0.0563:0.01-0.0834。
上述聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜的制备方法，包括以下步骤：(a)采用磷酸氢二铵和硝酸钙反应制备羟基磷灰石，将羟基磷灰石分散在去离子水中，再加入海藻酸钠混合均匀，得到经海藻酸钠稳定后的羟基磷灰石悬浮液；(b)用步骤(a)制备的经海藻酸钠稳定后的羟基磷灰石悬浮液分别配制得到含有羟基磷灰石的海藻酸钠溶液和含有羟基磷灰石的聚乙烯醇溶液；(c)将上述含有羟基磷灰石的海藻酸钠溶液和含有羟基磷灰石的聚乙烯醇溶液按比例混合均匀得含有羟基磷灰石、海藻酸钠和聚乙烯醇的纺丝液，利用纺丝液进行静电纺丝得到复合纤维膜。
上述方案中，制备羟基磷灰石的过程具体为：按照Ca/P＝1.67的摩尔比将磷酸氢二铵水溶液迅速倒入硝酸钙水溶液中，向混合溶液中滴加氨水调节溶液的pH至9-10，搅拌均匀后在80℃反应，经离心分离、多次水洗得羟基磷灰石白色沉淀。
优选的，磷酸氢二铵水溶液浓度为0.001-0.1mol/L，硝酸钙水溶液浓度为 0.00668-0.167mol/L。
上述方案中，制备羟基磷灰石悬浮液使用了超声进行分散，悬浮液中海藻酸钠的浓度为0.04-0.15mg/mL，羟基磷灰石浓度为1.67-16.7mg/mL。
上述方案中，在60-80℃配制质量分数为2％的海藻酸钠溶液以及质量分数为18％的聚乙烯醇溶液。
上述方案中，含有羟基磷灰石的海藻酸钠溶液和含有羟基磷灰石的聚乙烯醇溶液混合时的体积比为0.1-1:1-2。
上述方案中，静电纺丝的电压为10-15kv，接收距离为13-18cm，推进速度为0.03-0.05mm/min。
优选的，纺丝液中还加入了相当于聚乙烯醇、海藻酸钠和羟基磷灰石总质量1-5wt％的抗生素或生长因子。
上述聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜用作软组织损伤修复敷料的应用。
与现有技术相比，本发明的有益效果为：在不引入其他杂质的情况下，利用海藻酸钠结合超声法将羟基磷灰石稳定均匀的分散在水中，解决了羟基磷灰石易团聚的问题；利用静电纺丝法，通过有机、无机纳米复合技术，有机的结合了天然高分子与合成高分子材料的优良特性，制备出具有天然高分子、合成高分子生物相容性以及羟基磷灰石纳米粒子生物活性的复合纤维膜，该复合纤维膜可用作软组织损伤的修复敷料，并可装载抗生素或生长因子提高软组织损伤修复效果。
附图说明
图1为本发明实施例1中经海藻酸钠稳定后的羟基磷灰石悬浮液与未经处理过的羟基磷灰石分散液随时间的沉降照片图；
图2为本发明实施例1中经海藻酸钠稳定后的羟基磷灰石悬浮液与未经处理过的羟基磷灰石分散液透光率随时间变化的曲线图；
图3为本发明实施例1中经海藻酸钠稳定后的羟基磷灰石悬浮液的粒径图；
图4为本发明实施例2制备的复合纤维膜扫描电镜图；
图5为本发明实施例3制备的复合纤维膜扫描电镜图；
图6为本发明实施例4制备的复合纤维膜光学显微镜图；
图7为本发明实施例4制备的复合纤维膜荧光显微镜图。
具体实施方式
为使本领域普通技术人员充分理解本发明的技术方案和有益效果，以下结合具体实施例及附图进行进一步说明。应当理解，以下实施例仅为本发明较佳实施方式，并不构成对本发明的限定。
本发明提供一种聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜及其制备方法，具体如下：
首先配制浓度为0.001-0.1mol/L磷酸氢二铵溶液和浓度为0.00668-0.167mol/L硝酸钙溶液，按照Ca/P＝1.67的摩尔比将磷酸氢二铵水溶液迅速倒入硝酸钙水溶液中，向混合溶液中滴加氨水调节溶液的pH至9-10，搅拌均匀后在80℃反应，经离心分离、多次水洗得羟基磷灰石白色沉淀。将羟基磷灰石白色沉淀分散在去离子水中，再加入海藻酸钠超声混合分散，得到经海藻酸钠稳定后的羟基磷灰石悬浮液，其中海藻酸钠的浓度为0.04-0.15mg/mL，羟基磷灰石浓度为1.67-16.7mg/mL。
第二步用前述经海藻酸钠稳定后的羟基磷灰石悬浮液分别在60-80℃配制得质量分数为2％的海藻酸钠溶液以及质量分数为18％的聚乙烯醇溶液，且这两种溶液中含有的羟基磷灰石浓度为1.67-16.7mg/mL
最后将配制好的含有羟基磷灰石的海藻酸钠溶液和含有羟基磷灰石的聚乙烯醇溶液按0.1-1:1-2的体积比混合均匀得含有羟基磷灰石、海藻酸钠和聚乙烯醇的纺丝液，利用该纺丝液进行静电纺丝得到复合纤维膜，其中静电纺丝工艺参数为：电压10-15kv，接收距离13-18cm，推进速度0.03-0.05mm/min。按照本发明方法制备得到的复合纤维膜中聚乙烯醇、海藻酸钠、羟基磷灰石的质量比为1:0.01-0.0563:0.01-0.0834。该复合纤维膜可用作软组织损伤修复敷料，在纺丝液中加入抗生素或生长因子还可以提高软组织损伤修复效果。
实施例1
1)首先，分别配制浓度为0.0334mol/L的硝酸钙水溶液以及浓度为0.02mol/L的磷酸氢二铵水溶液。按照Ca/P＝1.67的摩尔比将20mL磷酸氢二铵水溶液迅速倒入20mL硝酸钙水溶液中，向混合溶液中滴加氨水，控制溶液pH为9-10，搅拌混合均匀。维持反应温度为80℃ 反应1h后，用去离子水重复离心三次得到白色沉淀物。将白色沉淀重新分散在40mL去离子水中得到浓度为1.67mg/mL的羟基磷灰石分散液，取20mL此分散液备用。取10mL去离子水和0.1g海藻酸钠配制质量分数为1％的海藻酸钠溶液，将0.08mL的海藻酸钠溶液加入到上述20mL分散液中，超声30s混合均匀，得到经海藻酸钠稳定后的羟基磷灰石悬浮液。
2)取两份步骤1)中得到的羟基磷灰石悬浮液10mL，分别加入0.2g海藻酸钠和1.8g聚乙烯醇，在80℃溶解，得到质量分数为2％的海藻酸钠(SA)溶液和质量分数为18％的聚乙烯醇(PVA)溶液，且这两种溶液中含有羟基磷灰石浓度为1.67mg/mL。
3)取上述2％的SA溶液2mL和18％的PVA溶液6mL，将两者混合均匀后在12kv电压、15cm接收距离、0.04mm/min的推进速度下进行静电纺丝，得到聚乙烯醇/海藻酸钠/羟基磷灰石的纤维膜。此复合纤维膜中聚乙烯醇、海藻酸钠、羟基磷灰石的质量比为1:0.037:0.0124。
本实施例步骤(1)中经海藻酸钠稳定后的羟基磷灰石悬浮液与未经处理过的羟基磷灰石分散液随时间的沉降照片如图1所示，其中左边为经海藻酸钠稳定后的羟基磷灰石悬浮液，右边为未经处理的羟基磷灰石分散液，a,b,c,d,e分别代表静置0h,1h,2h,5h,24h后的照片。通过对比可以很明显的看到，未经处理的羟基磷灰石分散液由于羟基磷灰石特别容易团聚的原因，在很短的时间内就发生了很明显的沉降，而经海藻酸钠稳定后的羟基磷灰石悬浮液可以保持较长时间的稳定。
本实施例步骤(1)中经海藻酸钠稳定后的羟基磷灰石悬浮液与未经处理过的羟基磷灰石分散液的透光率随时间变化的关系曲线如图2所示，从图中可以明显的看出未经处理的羟基磷灰石分散液(曲线a)由于颗粒的团聚引起的溶液不稳定而导致了透光率随时间的严重变化，从而得出经海藻酸钠稳定后的羟基磷灰石悬浮液比未经处理的羟基磷灰石分散液要稳定很多。
通过本实施例中经海藻酸钠稳定后的羟基磷灰石悬浮液的粒径图(图3)可以看出，我们所得到的羟基磷灰石的平均粒径为148nm，这也说明了羟基磷灰石得到了很好的分散。
实施例2
1)首先，分别配制浓度为0.0334mol/L的硝酸钙水溶液以及浓度为0.02mol/L的磷酸氢二铵水溶液。按照Ca/P＝1.67的摩尔比将20mL磷酸氢二铵水溶液迅速倒入20mL硝酸钙水溶液中，向混合溶液中滴加氨水，控制溶液pH为9-10，搅拌混合均匀。维持反应温度为80℃ 反应1h后，用去离子水重复离心三次得到白色沉淀物。将白色沉淀重新分散在40mL去离子水中得到浓度为1.67mg/mL的羟基磷灰石分散液，取20mL此分散液备用。取10mL去离子水和0.1g海藻酸钠配制质量分数为1％的海藻酸钠溶液，将0.08mL的海藻酸钠溶液加入到上述20mL分散液中，超声30s混合均匀，得到经海藻酸钠稳定后的羟基磷灰石悬浮液。
2)取两份步骤1)中得到的羟基磷灰石悬浮液10mL，分别加入0.2g海藻酸钠和1.8g聚乙烯醇，在80℃溶解，得到质量分数为2％的海藻酸钠(SA)溶液和质量分数为18％的聚乙烯醇(PVA)溶液，且这两种溶液中含有羟基磷灰石浓度为1.67mg/mL。
3)取上述2％的SA溶液2mL和18％的PVA溶液4mL，将两者混合均匀后在12kv电压、15cm接收距离、0.04mm/min的推进速度下进行静电纺丝，得到聚乙烯醇/海藻酸钠/羟基磷灰石的纤维膜。此复合纤维膜中聚乙烯醇、海藻酸钠、羟基磷灰石的质量比为1:0.056:0.0139。
本实施例制备的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜扫描电镜如图4所示，通过图片可以看出复合纤维形貌良好。
实施例3
1)首先，分别配制浓度为0.0334mol/L的硝酸钙水溶液以及浓度为0.02mol/L的磷酸氢二铵水溶液。按照Ca/P＝1.67的摩尔比将60mL磷酸氢二铵水溶液迅速倒入60mL硝酸钙水溶液中，向混合溶液中滴加氨水，控制溶液pH为9-10，搅拌混合均匀。维持反应温度为80℃反应1h后，用去离子水重复离心三次得到白色沉淀物。将白色沉淀重新分散在20mL去离子水中得到浓度为10.02mg/mL的羟基磷灰石分散液，备用。取10mL去离子水和0.1g海藻酸钠配制质量分数为1％的海藻酸钠溶液，将0.2mL的海藻酸钠溶液加入到上述20mL分散液中，超声30s混合均匀，得到经海藻酸钠稳定后的羟基磷灰石悬浮液。
2)取两份步骤1)中得到的羟基磷灰石悬浮液10mL，分别加入0.2g海藻酸钠和1.8g聚乙烯醇，在80℃溶解，得到质量分数为2％的海藻酸钠(SA)溶液和质量分数为18％的聚乙烯醇(PVA)溶液，且这两种溶液中含有羟基磷灰石浓度为10.02mg/mL。
3)取上述2％的SA溶液2mL和18％的PVA溶液4mL，将两者混合均匀后在12kv电压、15cm接收距离、0.04mm/min的推进速度下进行静电纺丝，得到聚乙烯醇/海藻酸钠/羟基磷灰石的纤维膜。此复合纤维膜中聚乙烯醇、海藻酸钠、羟基磷灰石的质量比为1:0.056:0.0834。
本实施例制备的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜扫描电镜如图5所示，通过图片可以看出复合纤维形貌良好。
实施例4
1)首先，分别配制浓度为0.0334mol/L的硝酸钙水溶液以及浓度为0.02mol/L的磷酸氢二铵水溶液。按照Ca/P＝1.67的摩尔比将20mL磷酸氢二铵水溶液迅速倒入20mL硝酸钙水溶液中，向混合溶液中滴加氨水，控制溶液pH为9-10，搅拌混合均匀。维持反应温度为80℃反应1h后，用去离子水重复离心三次得到白色沉淀物。将白色沉淀重新分散在40mL去离子水中得到浓度为1.67mg/mL的羟基磷灰石分散液，取20mL此分散液备用。取10mL去离子水和0.1g海藻酸钠配制质量分数为1％的海藻酸钠溶液，将0.08mL的海藻酸钠溶液加入到上述20mL分散液中，超声30s混合均匀，得到经海藻酸钠稳定后的羟基磷灰石悬浮液。
2)取两份步骤1)中得到的羟基磷灰石悬浮液10mL，分别加入0.2g海藻酸钠和1.8g聚乙烯醇，在80℃溶解，得到质量分数为2％的海藻酸钠(SA)溶液和质量分数为18％的聚乙烯醇(PVA)溶液，且这两种溶液中含有羟基磷灰石浓度为1.67mg/mL。
3)取上述2％的SA溶液2mL和18％的PVA溶液4mL混合，再加入5％(0.0385g)的盐酸四环素并混合均匀，在12kv电压、15cm接收距离、0.04mm/min的推进速度下进行静电纺丝，得到装载盐酸四环素的聚乙烯醇/海藻酸钠/羟基磷灰石的纤维膜。此复合纤维膜中聚乙烯醇、海藻酸钠、羟基磷灰石和盐酸四环素的质量比为1:0.056:0.0139:0.0535。
本实施例制备的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜光学显微镜图、荧光显微镜图如图6-7所示。通过复合纤维膜光学显微镜图可以看出纤维形貌良好，通过复合纤维膜荧光显微镜图可以看出盐酸四环素的特有荧光，说明其已成功的被载入到了复合纤维膜里面。

Claims (10)

  1. 一种聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜，其特征在于：该复合纤维膜中聚乙烯醇、海藻酸钠、羟基磷灰石的质量比为1:0.01-0.0563:0.01-0.0834。
  2. 权利要求1所述的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜的制备方法，其特征在于，包括以下步骤：(a)采用磷酸氢二铵和硝酸钙反应制备羟基磷灰石，将羟基磷灰石分散在去离子水中，再加入海藻酸钠混合均匀，得到经海藻酸钠稳定后的羟基磷灰石悬浮液；(b)用步骤(a)制备的经海藻酸钠稳定后的羟基磷灰石悬浮液分别配制得到含羟基磷灰石的海藻酸钠溶液和含羟基磷灰石的聚乙烯醇溶液；(c)将上述海藻酸钠溶液和聚乙烯醇溶液按比例混合均匀得含有羟基磷灰石、海藻酸钠和聚乙烯醇的纺丝液，利用纺丝液进行静电纺丝得到复合纤维膜。
  3. 如权利要求2所述的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜的制备方法，其特征在于，制备羟基磷灰石的过程具体为：按照Ca/P＝1.67的摩尔比将磷酸氢二铵水溶液迅速倒入硝酸钙水溶液中，向混合溶液中滴加氨水调节溶液的pH至9-10，搅拌均匀后在80℃反应，经离心分离、多次水洗得羟基磷灰石白色沉淀。
  4. 如权利要求3所述的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜的制备方法，其特征在于：磷酸氢二铵水溶液浓度为0.001-0.1mol/L，硝酸钙水溶液浓度为0.00668-0.167mol/L。
  5. 如权利要求2所述的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜的制备方法，其特征在于：制备羟基磷灰石悬浮液使用了超声进行分散，悬浮液中海藻酸钠的浓度为0.04-0.15mg/mL，羟基磷灰石浓度为1.67-16.7mg/mL。
  6. 如权利要求2所述的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜的制备方法，其特征在于：在60-80℃配制质量分数为2％的海藻酸钠溶液以及质量分数为18％的聚乙烯醇溶液。
  7. 如权利要求2所述的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜的制备方法，其特征在于：海藻酸钠溶液和聚乙烯醇溶液混合时的体积比为0.1-1:1-2。
  8. 如权利要求2所述的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜的制备方 法，其特征在于：静电纺丝的电压为10-15kv，接收距离为13-18cm，推进速度为0.03-0.05mm/min。
  9. 如权利要求2-8任一项所述的聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜的制备方法，其特征在于：纺丝液中还加入了相当于聚乙烯醇、海藻酸钠和羟基磷灰石总质量1-5wt％的抗生素或生长因子。
  10. 权利要求1所述聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜用作软组织损伤修复敷料的应用。
PCT/CN2017/071507 2017-01-16 2017-01-18 聚乙烯醇/海藻酸钠/羟基磷灰石复合纤维膜及其制备方法、应用 WO2018129761A1 (zh)

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