CN105999359B - A kind of external application dressing and its preparation method and application - Google Patents
A kind of external application dressing and its preparation method and application Download PDFInfo
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- CN105999359B CN105999359B CN201610393435.6A CN201610393435A CN105999359B CN 105999359 B CN105999359 B CN 105999359B CN 201610393435 A CN201610393435 A CN 201610393435A CN 105999359 B CN105999359 B CN 105999359B
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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
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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
- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
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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
- A61L15/22—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
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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
- A61L15/22—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
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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
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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
- A61L15/64—Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
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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
- 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
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
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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
- 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
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Abstract
The present invention provides a kind of external application dressing and its preparation method and application.External application dressing of the invention is formed by composite fibre, and the composite fibre includes: A. synthetic polymer, B. natural polymer and C. Deferoxamine.The method for being used to prepare the external application dressing includes that solution, the solution comprising natural polymer and Deferoxamine comprising synthetic polymer are mixed to form spinning material liquid, then carries out spinning processing to the spinning material liquid.The present invention also provides application of the external application dressing in the product for being used to prepare treatment skin injury.
Description
Technical field
This patent disclosure relates generally to medical fields, and more specifically, the present invention relates to one kind can promote the outer of wound repair
With dressing, it is clean which can not only keep the surface of a wound to do, moreover it is possible to effectively facilitate angiogenesis, healing acceleration process.The present invention is also
The preparation method for providing the external application dressing and its application in terms of skin injury treatment.
Background technique
The committed step of skin wound healing is that new vessels grow into the surface of a wound and granulation tissue is formed, for some common
Trauma wound wraps up it and is protected and taken orally simultaneously or external medication can be so that wound be able to using dressing
Rehabilitation.And for the surface of a wound of some chronic refractory conjunctions, for example, diabetic the pedal skin surface of a wound, long-term bedridden patients and draw
Skin bedsore wound etc. is played, passes through dressing and the common gauze dressing of covering merely, it is difficult to achieve the purpose that wound healing, and be easy
Ulcer is caused to be formed.To the pedal skin surface of a wound of diabetic, amputation need to be finally selected to control ulcer expansion and burst
The repeated infection in ulcer face.Data shows that therefore it is about 1,000,000 people that the whole world loses the patient of side lower limb every year, almost every 30 seconds
In just have a patient and lose lower limb because of diabetes, and the number is also passed because diabetes morbidity increases year by year
Increase.
After skin trauma, damage zone blood supply is further damaged, be cause skin wound to be difficult to heal spontaneously it is main because
One of element especially shows that original there is the patient of blood supply obstacle (such as diabetic, advanced age)；Stimulate skin injury area blood
Dermal layer of the skin blood supply is rebuild in pipe regeneration, is the impetus for promoting the healing of skin refractory often to select.In recent years, numerous special
Family scholar is included in animal experiment by various methods to promote damage field vascularization and attempts intraperitoneal injection or part drop
The method of addition blood vessel relevant cell extrinsic factor (biological agent) and/or drug.These behaves promote angiogenesis increasing really
The effect for being conducive to damage location wound healing is played mostly and to a certain extent, but its disadvantage deficiency is also obviously.It is first
First, the utilization rate of related drugs and extracellular growth factors (biological agent) is low, and the medication amount for really reaching damage location is unknown；
Secondly, other histoorgans can be caused new complication occur using the method for intraperitoneal injection, risk is excessively high.And use part
It is added dropwise or the method for injection can then cause affected part pain, stimulation and latent infection risk etc..
For diabetic, while systematicness controls blood glucose level, skin injury part is increasingly laid particular emphasis on
Treatment, wound negative pressure drainage (negative pressure wound therapy/NPWT) is existing frequently-used part
One of the method for treating the acute and chronic wound of refractory.Vacuum suction therapy passes through the sepage of mitigation wound district and tissue edema, suppression
The effects of bacterial growth processed and mechanical force emergency cause granulation tissue formation, angiogenesis, promotes wound healing, and show and face
Bed curative effect.But with the increase for the treatment of idicatio, some new problems need further to be studied, and such as most suitable negative pressure value, dressing are more
Change time, reasonable treatment time etc..Except this, also constantly there is new pattern compress as temporary skin substitute for flap coverage
It researches and develops product to come out, such as artificial skin.Since the high saccharide ring border of Tissue of Diabetic Wound hinders the reconstruction of microvasculature, Jin Jintong
It crosses and not can effectively solve this problem using the biomaterial with biomimetic features.Therewith, people attempt by it is some have induce
Cell factor [such as vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), matrix of vascularization effect
- 1 α of cell derived factor (SDF), etc.] be added in the dressing of biomaterial, recombination PDGF-BB is a kind of present only warp
U.S. FDA certification is crossed, can be used for the growth factor of clinical skin repair, application method clinically is will to carry at present
The gel of PDGF-BB is applied to surface of a wound Chu Lai repairing skin tissue.But due to the pathology machine of the refractories skin wound such as diabetes
System is complicated, only cannot highly effective acceleration wound healing by one to two kinds of growth factors of addition；Exogenous growth extrinsic factor valence
Lattice are expensive.Also be in following deficiency with regard to recombination PDGF-BB: 1, this load medicine and therapeutic modality still fall within traditional part and use
The scope of medicine, patient activity, covering dressing (such as gauze) and local friction can lead to gel effective component loss, reduce and treat
Effect；2, the contained drug of gel can not be sustained, and because gel has collapsing loss, can not accurately calculate drug release effect.3, in recent years
The report mostly occurred about its possible induced cancer.
Histocyte hypoxemia/hypoxia inducible factor (hypoxia-inducible factor, HIF)-α access is activated, is opened
It moves downstream with the direct target gene of vascularization blood vessel (VEGF, SDF-1 α etc.), it can obvious stimulation tissue blood vessel new life.It is based on
This mechanism seeks medicinal hypoxia-mimicking compound to promote regeneration and repair, is the hot spot of current Related Research Domain
Content.Deferoxamine (DFO) is used as iron ion complexing agent, starts to be applied to clinic in the 1970's, is mainly used for treating hemochrome
The disease due to transfusional chronic iron overloading such as thesaurismosis and thalassemia, sickle cell anemia.In recent years, Shen
Please person and it is relevant the study found that DFO can by iron ion needed for complexing HIF- α metabolic process, and active cell hypoxemia/
It is newborn to stimulate the tissue blood vessel of bone and soft tissue, and then plays and promotes the effect of HIF- α access, presentation hypoxia-mimicking compound
The effect of regeneration and reparation.Therefore, the biomaterial of application load DFO has clear advantage as Wound dressing.The
One, DFO are used for many years clinically as endo-medicine, highly-safe；Second, DFO extract from the day of Streptococcal fermentation liquid
Right object, stability is good, and failure is not easily decomposed during being mixed with material；Third, DFO, which have, to be promoted recruiting cells, increases
The effect grown and survived, adjustable ganglion cell cytokine profiles expression relevant to vascularization.
Union of wounded skin is continuous biology cascade reaction process, the histology advantage table according to its different phase
It is existing, skin healing preliminary process can be roughly divided into three phases.First stage: the surface of a wound formed after the 1st~3 day, main table
It is now the inflammatory reaction in skin wound area, with the leukocyte infiltration based on slurries exudation, congested and neutrophil leucocyte；Second
Stage: the surface of a wound formed after the 3rd~14 day, granulation tissue hyperplasia is obvious, and angiogenesis, microvasculature are rebuild, collagen
It is formed, newborn connective tissue gradually fills the full surface of a wound；Phase III: the surface of a wound formed after the 3rd~21 day, basal cell constitute
Simple epithelium covers granulation tissue surface, collagen recombination etc..Therefore, Wound dressing should at least have two features: vasotropic
Drug should be in early stage quick release, and to raise cell and its reach damage field at the relevant cell of blood vessel and the factor, being will
The reconstructing blood vessel of beginning provides basis；Stock support can degrade in due course, otherwise will become the barrier of new tissue growth, creeping substitution
Hinder.It needs to develop the external application dressing that can satisfy above-mentioned requirements in the prior art.
Summary of the invention
The critical issue intended to solve when in view of refractory skin injury treatment, it is deposited that the present invention develops a kind of Novel external
Material designs and utilizes spining technology, particularly electrostatic spinning technique in the base starting material of DFO incorporation medical macromolecular materials,
It is prepared for a kind of porous dressing of Hydrophilic Nanofibrous film containing DFO, by the component parameter of adjusting bracket material, applies this
Material can quick release DFO therein (24 hours total burst sizes are up to 80%；72 hours total burst sizes are effectively sent out up to 100%)
DFO is waved to raise cell, induce blood vessel and promote the effect of granulation tissue growth；Timbering material has and healing speed phase
The degradation speed matched, in the second period of skin wound reparation, (granulation tissue hyperplasia is obvious, angiogenesis, microvasculature weight
New building, collagen are formed, and newborn connective tissue gradually fills the full surface of a wound) degradable (at the 8th day, nearly 80% degradation；10 days
When, almost degrade)；The material also has many characteristics, such as hydrophily, porous permeability, is conducive to keep the surface of a wound dry clear
It is clean.
The first aspect of the invention provides a kind of external application dressing, which is formed by composite fibre, described multiple
Condensating fiber includes:
A. synthetic polymer, it is fine which is selected from polyvinyl alcohol, pla-pcl, silicon rubber, polyurethane, polyester
Dimension, polyvinylpyrrolidone, polyether-ether-ketone, polymethyl methacrylate, polylactic acid, polyethylene and their combination；
B. natural polymer, the natural polymer are selected from chitosan, cellulose, hyaluronic acid, collagen, gelatin, sea
Mosanom and their combination；
C. Deferoxamine.
According to embodiment of the present invention, it is counted on the basis of the total weight of the composite fibre, the Deferoxamine
Content is 0.8-1.05 weight %, preferably 0.9-1.03 weight %, more preferable 0.95-1.02 weight %, more preferably 0.99-
1.01 weight %, most preferably 1 weight %.
According to another implementation of the invention, it is counted on the basis of the total weight of the composite fibre, the synthesis is poly-
Close object content be 1-98 weight %, preferably 5-90 weight %, more preferable 10-85 weight %, more preferable 20-70 weight %, more
It is preferred that 30-60 weight %, more preferable 40-55 weight %；The content of the natural polymer is 1-98 weight %, preferably 5-90 weight
Measure %, more preferable 10-85 weight %, more preferable 20-70 weight %, more preferable 30-60 weight %, more preferable 40-55 weight %.
According to another implementation of the invention, the synthetic polymer is polyvinyl alcohol, degree of polymerization 2400-
2500, degree of hydrolysis 98.0-99.8mol%；The natural polymer is chitosan, molecular weight 10,000-200,000,
Preferably 30,000-80,000, more preferably 40,000-70,000, deacetylation 90-95%.
According to embodiment of the present invention, the diameter of the composite fibre be 50 nanometers to 50 microns, preferably 100
Nanometer is to 1000 microns, more preferably 500-900 nanometers, more preferably 600-800 nanometers；The water contact angle of the composite fibre
For 0-5 degree, preferably 0-2.5 degree, more preferably 0 degree.
The second aspect of the invention provides a kind of method for manufacturing external application dressing of the invention, and feature exists
In, method includes the following steps:
(i) solution comprising the synthetic polymer is provided；
(ii) solution comprising the natural polymer is provided；
(iii) solution of step (i), the solution of step (ii) and Deferoxamine are mixed, forms spinning material liquid；
(iv) spinning operation is carried out to the spinning material liquid, forms the dressing formed by composite fibre.
According to embodiment of the present invention, for the step (i), solution is formed using solvent selected from the following:
Water, methanol, ethyl alcohol, propyl alcohol, butanol, dimethyl ether, ether and their mixture；With the total of the solution of the step (i) formation
It is counted on the basis of weight, the concentration of synthetic polymer is 2-15 weight % in the solution.
According to another implementation of the invention, it for the step (ii), is formed using solvent selected from the following molten
Liquid: water, methanol, ethyl alcohol, propyl alcohol, butanol, dimethyl ether, ether and their mixture；It is formed with the step (ii) molten
It is counted on the basis of the total weight of liquid, the concentration of natural polymer is 0.5-5 weight % in the solution.
According to another implementation of the invention, optionally, the step (ii) formed solution in be added acid or
Alkali promotes to dissolve；The acid is selected from: formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, ethanedioic acid, malonic acid, glutaric acid, oneself
Diacid, hydrochloric acid, sulfuric acid, nitric acid and their mixture.
According to another implementation of the invention, Deferoxamine is added molten made from the step (i) or step (ii)
Then liquid carries out the mixing of the step (iii)；
According to another implementation of the invention, it is with the total weight of the step (iii) spinning material liquid formed
Benchmark meter, the concentration of synthetic polymer is preferably 5-12 weight %, more preferably 7-10 weight % in the spinning material liquid, most
Preferably 8.8 weight %；It is counted on the basis of the total weight of the spinning material liquid formed by the step (iii), the spinning material liquid
The concentration of middle natural polymer is 1-4 weight %, preferably 1.5-3 weight, more preferably 2 weight %.
According to another implementation of the invention, for step (iv), the spinning operation is by selected from the following
What technology carried out: electrostatic spinning, nonwoven fabric technology, three dimensional weaving technique.
According to another implementation of the invention, the external application dressing with a thickness of 10-1000 microns, preferably 50-
800 microns, more preferably 200-600 microns, more preferably 500 ± 20 μm.
According to another implementation of the invention, the stretching tension intensity of the external application dressing is 0.8-5MPa, preferably
For 1.81 ± 0.28MPa.
The third aspect of the invention provides external application dressing of the invention in the product of preparation treatment skin injury
Using the wound includes common trauma wound, refractory wound, burn wound and diabetic keratopathy wound.
Detailed description of the invention
The principle of the present invention and embodiment are described in conjunction with attached drawing in the present invention.
Figure 1A is shown in the present invention for carrying out the electrospinning device of spinning operation；
Figure 1B shows the bulk fabric manufactured according to one embodiment of the present invention；
Fig. 1 C shows the fritter fabric cut from the bulk fabric of Fig. 2 B, may be used as external application of the invention and applies
Material；
Fig. 2A is the scanning electron microscope (SEM) photograph of 20,000 times of dressing amplifications according to one embodiment of the present invention；
Fig. 2 B is the scanning electron microscope (SEM) photograph of 10,000 times of dressing amplifications according to one embodiment of the present invention；
Fig. 3 is the Deferoxamine releasing curve diagram of dressing according to one embodiment of the present invention；
Fig. 4 shows the external degradation performance of dressing according to one embodiment of the present invention
Fig. 5 is the experimental result of Cell culture invitro according to one embodiment of the present invention；
Fig. 6 is the cytotoxicity testing result that cell culture experiments in vitro obtains and at vessel properties detection figure；
Fig. 7 show respectively using control dressing and the healing of the diabetes rat back surface of a wound of dressing of the invention covering into
Journey；
Fig. 8 shows Diabetic Rat Wound Skin slice H&E coloration result；
Fig. 9 shows the influence that vegf protein is expressed in dressing according to one embodiment of the present invention；
Figure 10 shows the relationship of de-iron amine concentration and cytotoxicity in dressing according to one embodiment of the present invention.
Specific embodiment
It will the present invention is further described in detail in the following contents.It should be noted however that below
Specific embodiment only provides concrete operations example of the invention in an exemplary fashion, but protection scope of the present invention is not
It is only limitted to this.Protection scope of the present invention is only limited only by the claims that follow.Those skilled in the art can be apparently
Expect, can claims of the present invention limit protection scope within to embodiment of the present invention carry out it is various its
Its improvement and replacement, and still be able to realize identical technical effect, reach the ultimate technical purpose of the invention.
In the present invention, unless indicated to the contrary, all ratios are weight ratio, and all percentage is attached most importance to
Measure percentage, the unit of temperature is DEG C that the unit of pressure is pa.Room temperature refers to environment temperature conventional in laboratory, with season and
Change in location, usually 25 DEG C.In addition, all numberical ranges that the present invention describes include end value and may include that will disclose
Range the obtained new numberical range of the mutual any combination of upper and lower bound.For example, if disclosing the weight of certain component
Amount percentage composition is 10~30 weight %, preferably 15~25 weight %, more preferable 20~23 weight %, then is equivalent to while open
Numberical range below: 10~15 weight %, 10~25 weight %, 10~20 weight %, 10~23 weight %, 15~30 weights
Measure %, 15~20 weight %, 15~23 weight %, 20~25 weight %, 23~25 weight %.
The present invention uses Deferoxamine as therapeutic activity component, is incorporated into spinning material liquid, passes through spinning technique
It is prepared for the fabric dressing containing Deferoxamine active constituent.
Deferoxamine has structure shown in following formula (1).There is no in the art Deferoxamine (DFO) is fixed on it is compound
For use as the report of the active component of solid dressing in fiber.
Formula (1) Deferoxamine
Dressing of the invention is the form for the fabric being made of composite fibre, and in the present invention, dressing is considered as activity
The carrier or bracket of component Deferoxamine, therefore in the following description, term " dressing ", " fabric ", " bracket " and " carrier "
It may be used interchangeably, be used to indicate dressing of the present invention.In addition, term " fiber " and " spinning " may be used interchangeably.
Below in an example using polyvinyl alcohol and chitosan as the specific example of the synthetic polymer and natural polymer, but
Being can also be using other synthetic polymer and natural polymer with similarity.
Dressing of the invention is prepared by spinning technique.Specifically, by the selected synthetic polymer of the present invention, natural
Polymer is respectively formed in the form of water or the solution in other suitable solvents, then mixes both solution with Deferoxamine,
Form the material liquid for being used for spinning technique.When preparing the solution of the polymer, it can according to need in the solution
Additionally incorporate other additives, the example of these additives includes below one or more: pH adjusting agent, is divided stabilizer
Powder, tackifier.According to embodiment of the present invention, in the material liquid for spinning technique, in addition to above-mentioned Deferoxamine,
Other than natural polymer and synthetic polymer, other components are not included.
According to embodiment of the present invention, the Deferoxamine can be used as individual component and the natural polymerization
The solution mixing of the solution and synthetic polymer of object.Another embodiment according to the present invention, can be first by Deferoxamine
It is added in any one in the solution of the natural polymer and the solution of synthetic polymer, then by resulting solution
It is mixed with another polymer solution.
After preparing spinning material liquid, material liquid is woven into dressing of the invention by spin processes.The spinning skill
Art can use method of electrostatic spinning, nonwoven fabric technology, and three dimensional weaving technique etc. carries out, by select suitable spining technology and
The type and concentration of various raw materials in spinning material liquid, so that fabric product obtained has certain mechanical strength, bio-compatible
Property it is excellent, can payload drug and can according to required requirement to active constituent carry out gradient release.In implementation below
Method of electrostatic spinning is used in example, Fig. 1 shows a kind of conventional electrospinning device, which includes syringe pump, high voltage power supply
With Rotation of receiver plate.There is injection needle, high voltage power supply one end is connected with the syringe needle, other end connection below the syringe pump
Rotation of receiver plate is simultaneously grounded.During spinning operation, the spinning material liquid prepared in advance is projected from syringe needle, in electric field action
Under, the drop at syringe needle can be become conical (i.e. " taylor cone ") from spherical shape, and extend to obtain fiber filaments from conical tip.Under
The Rotation of receiver plate at end is connected with computer-controlled mechanical mobile device, can carry out the rotation of optional frequency and amplitude as required
Turn, vibration, translation etc. movement so that the fiber filaments from syringe pump syringe needle is formed on the Rotation of receiver plate fabric dressing produce
Product.
It is of the invention although specifically combining electrostatic spinning that method of the invention is described in the embodiment of the present invention
Protection scope be not limited in a kind of this specific spinning technique.
Technical solution of the present invention is specifically described below in conjunction with embodiment.
Embodiment
Deferoxamine used in following synthetic example, polyvinyl alcohol and Chitosan are purchased from Sigma company, wherein gathering
Vinyl alcohol is medical grade, and degree of polymerization 2400-2500, degree of hydrolysis 98.0-99.8mol%, chitosan is medical grade, is gone
Acetyl degree is 90-95%；Remaining chemical reagent is purchased from companies such as the Delhi sigma-Ai Er odd (Sigma-Aldrich)
Analytical grade reagent；Used water is deionization double distilled water.Reaction carries out under normal temperature and pressure conditions.Reaction uses quiet
Electrospinning device has present invention structure shown in FIG. 1, and wherein high voltage power supply is purchased from Tianjin Dong Wen company, and syringe pump is purchased from Baoding
Seiko pumps industry.
Embodiment 1: the preparation of dressing
In this embodiment, the solution of the 8 weight % of medical grade polyvinyl alcohol in deionized water is prepared.Independently will
Medical chitosan is dissolved in the acetic acid aqueous solution of 1 weight % with the concentration of 2 weight %, and meter in advance is added into the chitosan solution
The Deferoxamine solid powder of calculation amount, forms chitosan solution, and the additional amount of the Deferoxamine makes the Deferoxamine in final dressing
Content accounts for the 1% of dressing total weight of solids.By the poly-vinyl alcohol solution of made as described above and chitosan solution with the weight of 4:6
Than mixing, it is placed in syringe pump.Using present invention electrostatic spinning machine shown in FIG. 1, select 0.6mm stainless steel syringe needle as spinning
Silk injector head simultaneously connects high pressure positive electrode, and Rotation of receiver plate is being arranged at syringe needle 8cm.Voltage control is in 12kV and keeps room
25 degree of temperature carries out electrospinning with the speed of 0.4ml/h, obtains dressing of the invention.
In addition, applicant also repeats the above steps, change the additional amount of Deferoxamine, having obtained de-iron amine concentration is 0.3 weight
Measure the dressing of %, 0.6 weight, 0.8 weight %, 0.9 weight %, 1.0 weight %, 1.1 weight %, 1.2 weight %, above-mentioned content
Total solids meter based on product dressing.
Figure 1B shows fabric made from 1 through the embodiment of the present invention, with a thickness of 500 ± 20 μm；Bulk fabric cutting
At fritter fabric shown in Fig. 1 C, for subsequent test and characterization.Can according to need will be after above-mentioned bulk fabric or cutting
Fritter fabric be used as dressing.Fig. 2A and 2B respectively illustrates dressing of the present invention under 20000 times and 10000 times of amplification factors
Scanning electron microscope (FEI, USA) image, from the figure, it can be seen that fibre diameter is more unified, the diameter of fiber is 716.5 ±
76.1nm, and reticular structure is connected at random.DFO can be well soluble in nanofiber, be gone out without obvious impurity and drop
It is existing.Measured (optical contact angle measuring instrument；Kruss, Germany) water contact angle (WCA) be 0 °, show good hydrophilic
Property.The stretching tension intensity of bracket is 1.81 ± 0.28MPa, and mechanical property can be used for the suture covering of skin.
Embodiment 2: control dressing (dressing without Deferoxamine)
In the present embodiment, the preparation step for repeating embodiment 1 forms dressing, but differs in that, is not used in raw material
Deferoxamine, dressing obtained are denoted as control dressing.
Embodiment 3: in this embodiment, the present invention with different de-iron amine contents prepared using above embodiments 1
Dressing has carried out the test of vegf protein expression performance.
Sample culturing
The dressing that DFO content is 0.8,0.9,1.0 weight % is cut into 15x15 millimeters2The square of size is preset in 6 holes
Board bottom, by 2x105Cell density is inoculated with skin fibroblasts, is placed in 37 DEG C, 5%CO2It is incubated in incubator, replaces every other day
Culture medium.In the 3rd day albumen extracted in cell of culture cell growth, each every group of at least three sample is repeated 3 times.
Protein extraction
The step of extracting albumen is as follows:
(1) 100 μ l RIPA (Beyotime, China) and 1 μ l protease inhibitors PMSF are added in the every hole cell of 6 orifice plates
(Beyotime, China)), it is placed on ice.
(2) with the careful scraping cells of cell scraper, cell is transferred in 0.5ml centrifuge tube, is placed 30 minutes on ice.
(3) 12000g revolving speed supercentrifuge, (Allegra X-22R Centrifuge, Beckman are used
Coulter, USA) it is centrifuged 15 minutes at 4 DEG C, it collects supernatant, be carefully transferred in sterile centrifugation tube, -80 DEG C save backup,
This is total protein of cell.
Protein concentration test
A part is taken out from above-mentioned total protein of cell, as follows, with BCA determination of protein concentration kit measurement egg
White concentration:
1. A liquid and B liquid are configured to working solution with the ratio of 50:1 in kit (Beyotime China) specification；
2. taking the BSA standard items of 2000 μ g/ml, 2000 μ g/ml, 1500 μ g/ml, 1000 μ are diluted to PBS (pH 7.4)
G/ml, 750 μ g/ml, 500 μ g/ml, 250 μ g/ml, 125 μ g/ml, 25 μ g/ml, 10 μ g/ml totally 9 concentration gradients；
3. taking 10 μ l of protein extract, 10 times are diluted with PBS；
4. the histone extracting solution after every 100 μ l protein standard substance of Guan Zhongjia or dilution, along with stating working solution 2ml,
37 DEG C are incubated for 30 minutes, and absorbance is surveyed at 562nm, record OD value；
5. drawing standard curve according to OD value and protein standard substance concentration, sample total protein concentration is calculated.
Encapsulating
Distilled water cleans encapsulating glass plate, dries vertically.10% separation gel 10ml is prepared, 6 μ l of TEMED, 10%APS are added
150 μ l, encapsulating, filling to 2~3mm of stripping fork lower edge (mark) in advance immediately after mixing, with isopropanol closing liquid level to remove
Bubble simultaneously completely cuts off air, is stored at room temperature 45 minutes and polymerize completely to glue.After glue to be separated polymerize completely, incline at the top of it go from
Sub- water is blotted water with filter paper.5% concentration glue 6ml is prepared, adds 6 μ l of TEMED, 60 10%APS μ l, mixes encapsulating immediately, fill
To top, and it is inserted perpendicularly into Teflon stripping fork, is stored at room temperature 20 minutes and polymerize to glue.Comb is extracted after glue polymerize completely, it will
Gel is placed in electrophoresis tank, and electrophoretic buffer is added, and rinses loading hole with electrophoretic buffer to remove bubble removing.
Electrophoresis(electrophoresis apparatus, Bio-Rad, USA)
Each protein extract of above-mentioned separation is taken, adjusts protein concentration and the mixing of isometric 5 × sample-loading buffer, as
Sample solution.Sample solution is boiled 5 minutes in 100 DEG C of couveuses, makes albuminous degeneration, is quenched on ice, 3000 revs/min of centrifugations 1
Minute.Every hole adds 20 μ g of sample liquid, and a hole is stayed to add the Marker (Thermo, USA) of 10 μ l pre-dyed.Electrophoretic buffer is filled it up with, is covered
Upper slot cover, powers on, and first uses 70V constant pressure electrophoresis, about 30 minutes, uses 90V perseverance instead after indicator bromine Finland enters separation gel
Piezoelectricity swimming, power supply is closed when indicator is reached away from the about 0.5cm of gel lower end, takes out offset plate.
Transfer albumen and immune detection
Before electrophoresis closes to an end, in advance by pvdf membrane (Millipore, Germany) immersion 15 seconds in methyl alcohol, then
It is rinsed 2 minutes with double distilled water, is soaked in transfering buffering liquid and starts subsequent operation after five minutes.Glue is prized in water, is incited somebody to action after repairing glue
Glue is soaked in transfering buffering liquid and balances 15 minutes.By black flour (cathode) → sponge → filter paper → glue → pvdf membrane → filter paper → sea
Sequence preparation transferring film " sandwich " of continuous → red face (anode), every layer complete after first drive bubble away and repave another layer.It is slow in transfer
Sandwich is prepared in fliud flushing can avoid the generation of bubble.Connect positive and negative anodes, by film to anode direction by transfer box (Bio-Rad,
USA it) is put into electroporation, transferring film buffer is added.Electroporation is placed in ice water, 200mA constant current transferring film 90 minutes.Transferring film knot
Shu Hou quickly removes pvdf membrane, is put into 5% skim milk liquid chamber temperature and closes 1 hour.Film is taken out, in washing film 5 with TBST on shaking table
Minute × 3 times.The VEGF antibody (Novus, USA) (primary antibody) of confining liquid dilution (1:1000) is added in incubation bags and presses 1:5000
Diluted GAPDH antibody (health is century, China), 4 DEG C of overnight incubations.After TBST washes film 5 minutes × 3 times, horseradish peroxide is added
Compound enzyme (HRP) label, press the diluted anti-mouse secondary antibody (Abbkine, USA) of 1:5000, be incubated at room temperature 2 hours.TBST is washed
Film 15 minutes × 3 times.Develop in Image Quant LAS 4000mini machine, developer solution (Millipore Germany)
It prepares, reacts 2 minutes in 1:1 ratio for Millipore A, B liquid, take out film, get rid of extra liquid, detection reagent is added dropwise,
Photosensitive, development, fixing.
Test results are shown in figure 9 for vegf protein expression.The expression of vegf protein height is the necessary item for promoting angiogenesis
Part.It will be seen from figure 9 that vegf expression amount gradually increases with the increase of DFO content, promote angiogenesis.
Embodiment 4: the relationship of the content of Deferoxamine and dressing bio-toxicity in dressing
The dressing of different DFO contents is cut into 10x10mm respectively2The square of size is placed in 24 well culture plate bottoms, presses
According to 5x104Skin fibroblasts concentration inoculating cell, is placed in 37 DEG C, 5%CO2It is incubated in incubator, every other day replacement culture
Base.It is random in the 3rd day to take out 24 orifice plates, it removes original culture medium and is added and contain CCK-8 (Cell Counting Kit-8；
Dojindo Kagaku, Japan) culture medium (every 1ml fresh culture in contain 100 μ lCCK-8 solution)；Constant incubator
37 DEG C, 5%CO2After being incubated for two hours, absorbance value is detected at 450nm wavelength using microplate reader.At least three sample is taken every time
It is detected and is repeated 3 times.The results are shown in Figure 10.
It can see from the result of Figure 10, when DFO concentration is in 0.8wt%, 0.9wt%, 1.0wt% in dressing, with sky
White control group is compared, and drug does not have obvious cytotoxicity.However, cell Proliferation is obviously pressed down when DFO concentration continues to increase
System prompts drug concentration excessively high, inhibits cell growth, proliferation.Therefore, the dressing of 1.0wt% is selected, cytotoxicity is small and can
Effective stimulus fibroblasts to secrete VEGF promotes angiogenesis.
Embodiment 5: the characterization of Deferoxamine release performance
The performance that Deferoxamine is discharged from dressing is tested using following steps in this embodiment:
By 10 × 10 millimeters2The dressing (fibrous framework, de-iron amine content 1wt%) of size be completely soaked in 10ml 1 ×
In PBS solution (pH 7.4, room temperature) and continue stirring 5 days to ensure that the contained drug of bracket can discharge to greatest extent.Due to quiet
The distinctive high porosity of Electrospun bracket can absorb 315.8 ± 59.3% 1xPBS solution, shows after impregnating 12 hours in PBS
Stronger water imbibition is shown.
It draws a little solution and FeCl is added3So as in conjunction with the DFO in solution.Using EvolutionTM300 types
(Thermo Fisher, USA) ultraviolet-uisible spectrophotometer, at 485nm wavelength measure OD value and with DFO standard curve pair
Than obtaining DFO content in solution.It is compared with theoretical drugloading rate, obtains drug-loading efficiency.Branch is pre-processed with above-mentioned same procedure
Frame is simultaneously measured and is converted and obtain the DFO burst size of different time points, each medicine in the solution for drawing slight amount in preset time point
Object release experiment takes at least three sample and is repeated 3 times, and is averaged and draws medicament slow release curve.Experimental result is shown in Fig. 3.From Fig. 3
Release profiles can see, dressing of the invention can in 72 hours it is approximate realize 100% release, and first 24 hours
Burst size be up to 80% or more, thus meet wound restore needed for release performance requirement.
Embodiment 6: the external degradation performance detection of dressing of the present invention:
According to 0.1cm-1Area/volume ratio places a stent into 1 × PBS (7.4,37 DEG C of pH), and checks and accepts in preset time
Sampling is originally.Every group of three parts of samples are dried and are weighed in 40 DEG C of environment, are subsequently placed in 37 DEG C of incubators and are saved.It surveys every time
Before amount, sample is taken out from incubator and dries (40 DEG C) again.Degradation index (Di) based on weight loss situation by with
Lower formula, which calculates, to be obtained:
In the formula, W0Represent bracket original weight, WtRepresent the weight support frame of different soaking time points (t).Every group every
Secondary degradation experiment is selected at least three sample and is repeated 3 times, and is averaged and draws a diagram.Dressing degradation rate and its changing condition
As shown in Figure 4.In vitro, dressing is placed in PBS after 6 days, dry weight be about initial weight 60% (i.e. there are about 40% in vitro
Material be degraded), and be presented with the trend of fast degradation after 6 days；Dressing is placed in PBS after 8 days, and dry weight is about initial
30% (i.e. there are about 70% materials to be degraded in vitro) of weight；Dressing is placed in PBS after 10 days, the first starting weight of dry weight deficiency
10% (i.e. 90% or more material is degraded in vitro) of amount.Since the hydrophilic radical enhancing bracket in the dressing is integrally hydrophilic
Property, can fast degradation and reserve enough spaces be cambium the condition of offer is provided.
Embodiment 7: the influence that dressing grows cell
In this embodiment, dressing of the invention is detected to the primary epidermal cell strain of people and human umbilical vein by following steps
The influence of endothelial cell strain growth.
Cell climbing sheet is placed in 24 orifice plates, operates on ice and the matrigel without growth factor is uniformly laid on cell climbing sheet
On, 37 DEG C of constant incubator, 5%CO2After being incubated for 1 hour, 24 orifice plates are taken out, every hole 6x104(human umblilical vein endothelial is thin by HUVEC
Born of the same parents) be laid on matrigel, subsequent 0.4 μm of transwell of merging, by the embodiment of the present invention 1 prepare comprising 1wt% Deferoxamine
(DFO) sterilized dressing (fibrous framework) cuts into 10 × 10mm2The square of size is placed in upper chamber.It selects and contains 10% tire ox
Serum and 1% dual anti-DMEM high glucose medium carry out cell culture.In 37 DEG C, 5%CO2After being incubated for 4 hours, 12 hours respectively
24 orifice plates are taken out, transwell and dressing (fibrous framework) are removed, PBS is cleaned 3 times, and 10 minutes every time, 4% paraformaldehyde was solid
It is 15 minutes fixed.ZEISS Imager M1 (Germany) optical microscopy shoots photo, as shown in Figure 5.
It can be released effectively and promote into blood vessel for the DFO in detection dressing, we carry out tubule using HUVEC in vitro
Forming test is simultaneously compared with control group.As shown in figure 5, cell is gradually gathered into after the HUVEC of bracket group is intervened 4 hours
Group, and have tubule structures appearance, and the cell of control group is only assembled, and has no that obvious a large amount of capillary structures occur；It is small to intervene 24
Shi Hou, bracket group cell aggregation form the tubule of a large amount of thickenings and converge networking each other, and cellular control unit is effective due to lacking
At vascular stimulation object stimulate, although can also assemble in matrigel environment and have tubular structure appearance, Minute Tubule Structures are loose
And it cannot effectively converge networking.Result prompt carried stent can discharge DFO effective stimulus HUVEC in vitro at pipe.
Embodiment 8: toxicity and the biocompatibility detection of dressing of the present invention
In this embodiment, the dressing comprising 1wt% Deferoxamine that according to the following steps prepared by the detection embodiment of the present invention 1
And the toxicity and biocompatibility of the control dressing without Deferoxamine.
Dressing is cut into 10 × 10mm2The square of size is placed in 24 orifice plates, according to 5x104HFB cell concentration paving
Plate is placed in 37 DEG C, 5%CO2It is incubated in incubator, selects the DMEM high sugar culture dual anti-containing 10% fetal calf serum and 1%
Base carries out cell culture.Example of spatial compartmentalizationis (ingredient is same as above).Random respectively at the 1st, 2,3 day to take out 24 orifice plates, removal is former
There is culture medium and the culture medium containing CCK-8 (Dojindo Kagaku, Japan) is added and (contains 100 in every 1ml fresh culture
μ lCCK-8 solution).37 DEG C of constant incubator, 5%CO2After being incubated for two hours, suction is detected at 450nm wavelength using microplate reader
Shading value.It takes at least three sample to be detected every time and is repeated 3 times.As a result it as shown in fig. 6, as seen from Figure 6, and compares
Sample is non-toxic compared to dressing and has good biocompatibility.
Embodiment 9: therapeutic effect of the dressing of the present invention to skin of diabetic rats defect
In this embodiment, it the dressing comprising 1wt% Deferoxamine that is prepared respectively using the embodiment of the present invention 1 and is free of
Therapeutic effect of the control dressing of Deferoxamine to diabetes rat.
The 8 week old Sprague's-Du Le mouse (SD rat) that this experiment uses are bought by Shanghai SLAC experimental animal company.Greatly
The every 3 cages raising of mouse, ad lib water；Room temperature control is raised at 22 ± 2 DEG C.After adaptation in two weeks, randomly select
300-350g rat inducing type I diabetes model.Pre-assigned STZ solution (Sigma, the U.S.) is injected intraperitoneally according to 70mg/kg.
It is taken a blood sample by rat-tail weekly and detects blood glucose level.The rat that continuous six weeks blood glucose tills are maintained at 300mg/dl is identified as
Induce successful type-1 diabetes mellitus rat.
About 24 type-1 diabetes mellitus rats are selected at random.Pass through intraperitoneal injection according to the amount of liquid of 0.3ml/100g
2.5% yellow Jackets anaesthetize sb. generally.Fixed rat, shaves rat dorsum skin using animal electric shaver-for women, is used in combination
Nonirritant depilatory cream further loses hair or feathers, and sufficiently exposes operative region.70% sterile surgical area spreads aseptic towel, uses corneal ring
(Shanghai gold clock) is bored in the full cortex defect of circle of the drilled 15mm size in dorsal midline two sides, depth reaches on sarolemma.Cut phase
With the dressing of diameter, it is covered in the side surface of a wound, and is fixed with 4-0 suture silk.Then back is covered using sterile gauze
And it is fixed, preventing rat from baiting cause, it falls off.Whole surgical procedures aseptically carry out.Postoperative rat is individually raised
It supports, and has measured the key ring of diameter ring as a comparison in advance using 1.Dynamic observation wound healing situation.Postoperative rat wound 1
The photo of all (1W), 2 weeks (2W) and 3 weeks (3W) is as shown in Figure 7.After a week, the dressing group surface of a wound is obvious compared with control group healing rate
Accelerate, two group differences are obvious；After two weeks, the dressing group surface of a wound heals substantially, and control group is until test final time point (three weeks)
Terminate not yet healing completely.
In addition, the complete specimen collected around the surface of a wound and the surface of a wound including 3mm normal skin tissue in the postoperative 1st, 2,3 week.
It is fixed overnight using 4% paraformaldehyde.Automatic dehydrator (OXIS LX120 type；Leica, Germany) program dehydration, paraffin packet
It buries, is sliced (5 μm).It is sliced and is stayed overnight in the roasting piece of 60 DEG C of insulating boxs.The slice is handled according to the following steps:
H&E dyeing
(1) slice dewaxing: dimethylbenzene I, dimethylbenzene II dewax each 30 minutes.
(2) aquation: absolute alcohol I 5 minutes；Absolute alcohol II 5 minutes；95% alcohol I 5 minutes；95% alcohol II 5 minutes；
80% alcohol 5 minutes；70% alcohol 5 minutes；It is impregnated 5 minutes in tap water.
(3) it immerses in haematoxylin dye liquor 6 minutes.Tap water cleans haematoxylin.
(4) 1% hydrochloride alcohols break up 10 seconds.Tap water impregnates 6 minutes (it is primary that water is changed in centre) to abundant oil blackeite.
(5) Yihong solution dyes 2 minutes, washes respectively 1 minute in 85%, 95%, 95%, 100%, 100% ethyl alcohol, removes
Extra Yihong.
(6) transparent 1 minute of dimethylbenzene, neutral gum mounting.
(7) it microscopically observation and makes film, microphoto is as shown in Figure 8.
Interpretation of result:
We select newborn epidermis to creep apart from this objective index to understand wound healing situation.Selecting includes 3mm
The holostrome surface of a wound longitudinal direction paraffin section of normal skin tissue carries out H&E dyeing, observes the healing state of set time point.Such as Fig. 8
Shown, the surface of a wound is formed after a week, and granulation tissue hyperplasia is obvious at the dressing group surface of a wound, epithelialization progress faster；Meanwhile dressing is big
Portion's degradation, only has a small amount of residual at surface of a wound center；After two weeks, dressing group wound granulation tissue is obviously thickened compared with control group, quality
More preferably, newborn epithelium covers most surface of a wound；It can not be effectively observed dressing structure on morphology slice, prompted dressing
It is degradable.After three weeks, the dressing group surface of a wound heals completely, and granulation tissue morphology is close to normal tissue.And control group epithelialization
Process is still frangible compared with slow and granulation tissue weakness, prompts healing quality poor.
Claims (28)
1. a kind of external application dressing, which is formed by composite fibre, and the composite fibre includes:
A. synthetic polymer, the synthetic polymer are selected from polyvinyl alcohol, polycaprolactone, silicon rubber, polyurethane, polyester fiber, gather
Vinyl pyrrolidone, polyether-ether-ketone, polymethyl methacrylate, polylactic acid, polyethylene and their combination；
B. natural polymer, the natural polymer are selected from chitosan, cellulose, hyaluronic acid, collagen, gelatin, alginic acid
Sodium and their combination；
C. Deferoxamine is counted on the basis of the total weight of the composite fibre, and the content of the Deferoxamine is 0.8-1.05 weight %.
2. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating Deferoxamine is 0.9-1.03 weight %.
3. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating Deferoxamine is 0.95-1.02 weight %.
4. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating Deferoxamine is 0.99-1.01 weight %.
5. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating Deferoxamine is 1 weight %.
6. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating synthetic polymer is 1-98 weight %；The content of the natural polymer is 1-98 weight %；
The synthetic polymer is polyvinyl alcohol, degree of polymerization 2400-2500, degree of hydrolysis 98.0-99.8mol%；It is described
Natural polymer is chitosan, molecular weight 10,000-200,000, deacetylation 90-95%.
7. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating synthetic polymer is 5-90 weight %；The content of the natural polymer is 5-90 weight %；
The synthetic polymer is polyvinyl alcohol, degree of polymerization 2400-2500, degree of hydrolysis 98.0-99.8mol%；It is described
Natural polymer is chitosan, molecular weight 30,000-80,000, deacetylation 90-95%.
8. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating synthetic polymer is 10-85 weight %；The content of the natural polymer is 10-85 weight %；
The synthetic polymer is polyvinyl alcohol, degree of polymerization 2400-2500, degree of hydrolysis 98.0-99.8mol%；It is described
Natural polymer is chitosan, molecular weight 40,000-70,000, deacetylation 90-95%.
9. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating synthetic polymer is 20-70 weight %；The content of the natural polymer is 20-70 weight %；
The synthetic polymer is polyvinyl alcohol, degree of polymerization 2400-2500, degree of hydrolysis 98.0-99.8mol%；It is described
Natural polymer is chitosan, molecular weight 40,000-70,000, deacetylation 90-95%.
10. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating synthetic polymer is 30-60 weight %；The content of the natural polymer is 30-60 weight %；
The synthetic polymer is polyvinyl alcohol, degree of polymerization 2400-2500, degree of hydrolysis 98.0-99.8mol%；It is described
Natural polymer is chitosan, molecular weight 40,000-70,000, deacetylation 90-95%.
11. external application dressing as described in claim 1, which is characterized in that counted on the basis of the total weight of the composite fibre, institute
The content for stating synthetic polymer is 40-55 weight %；The content of the natural polymer is 40-55 weight %；
The synthetic polymer is polyvinyl alcohol, degree of polymerization 2400-2500, degree of hydrolysis 98.0-99.8mol%；It is described
Natural polymer is chitosan, molecular weight 40,000-70,000, deacetylation 90-95%.
12. external application dressing as described in claim 1, which is characterized in that the diameter of the composite fibre is 50 nanometers to 50 micro-
Rice；The water contact angle of the composite fibre is 0-5 degree.
13. external application dressing as described in claim 1, which is characterized in that the diameter of the composite fibre is 100 nanometers to 1000
Micron；The water contact angle of the composite fibre is 0-2.5 degree.
14. external application dressing as described in claim 1, which is characterized in that the diameter of the composite fibre is 500-900 nanometers；
The water contact angle of the composite fibre is 0-2.5 degree.
15. external application dressing as described in claim 1, which is characterized in that the diameter of the composite fibre is 600-800 nanometers；
The water contact angle of the composite fibre is 0 degree.
16. a kind of method for manufacturing the external application dressing as described in any one of claim 1-15, which is characterized in that the party
Method the following steps are included:
(i) solution comprising the synthetic polymer is provided；
(ii) solution comprising the natural polymer is provided；
(iii) solution of step (i), the solution of step (ii) and Deferoxamine are mixed, forms spinning material liquid；
(iv) spinning operation is carried out to the spinning material liquid, forms the dressing formed by composite fibre.
17. the method described in claim 16, which is characterized in that for the step (i), use solvent shape selected from the following
At solution: water, methanol, ethyl alcohol, propyl alcohol, butanol, dimethyl ether, ether and their mixture；It is formed with the step (i)
It is counted on the basis of the total weight of solution, the concentration of synthetic polymer is 2-15 weight % in the solution；
For the step (ii), solution: water, methanol, ethyl alcohol, propyl alcohol, butanol, diformazan is formed using solvent selected from the following
Ether, ether and their mixture；It is counted on the basis of the total weight of the solution formed by the step (ii), day in the solution
The concentration of right polymer is 0.5-5 weight %；
Acid or alkali is added in the solution that the step (ii) is formed to promote to dissolve；The acid is selected from: formic acid, acetic acid, propionic acid,
Butyric acid, valeric acid, caproic acid, ethanedioic acid, malonic acid, glutaric acid, adipic acid, hydrochloric acid, sulfuric acid, nitric acid and their mixture；
Solution made from the step (i) or step (ii) is added in Deferoxamine, then carries out the mixing of the step (iii)；
It is counted on the basis of the total weight of the spinning material liquid formed by the step (iii), synthetic polymer in the spinning material liquid
Concentration be 5-12 weight %；It is counted on the basis of the total weight of the spinning material liquid formed by the step (iii), the spinning material
The concentration of natural polymer is 1-4 weight % in liquid.
18. method as claimed in claim 17, which is characterized in that with the total of the step (iii) spinning material liquid formed
It is counted on the basis of weight, the concentration of synthetic polymer is 7-10 weight % in the spinning material liquid；With the step (iii) formation
Spinning material liquid total weight on the basis of count, in the spinning material liquid concentration of natural polymer be 1.5-3 weight %.
19. method as claimed in claim 17, which is characterized in that with the total of the step (iii) spinning material liquid formed
It is counted on the basis of weight, the concentration of synthetic polymer is 8.8 weight % in the spinning material liquid；It is formed with the step (iii)
It is counted on the basis of the total weight of spinning material liquid, the concentration of natural polymer is 2 weight % in the spinning material liquid.
20. the method described in claim 16, which is characterized in that for step (iv), the spinning operation is by being selected from
What technology below carried out: electrostatic spinning.
21. the method described in claim 16, which is characterized in that the external application dressing with a thickness of 10-1000 microns.
22. the method described in claim 16, which is characterized in that the external application dressing with a thickness of 50-800 microns.
23. the method described in claim 16, which is characterized in that the external application dressing with a thickness of 200-600 microns.
24. the method described in claim 16, which is characterized in that the external application dressing with a thickness of 500 ± 20 microns.
25. the method described in claim 16, which is characterized in that the stretching tension intensity of the external application dressing is 0.8-
5MPa。
26. the method described in claim 16, which is characterized in that the stretching tension intensity of the external application dressing be 1.81 ±
0.28MPa。
27. application of the external application dressing in the product of preparation treatment skin injury as described in claim 1-15, the wound
Including common trauma wound and refractory wound.
28. application as claimed in claim 27, which is characterized in that the wound includes burn wound and diabetic keratopathy wound.
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| CN106620813A (en) * | 2016-12-26 | 2017-05-10 | 苏州大学 | Preparation method of medical antibacterial nano dressing |
| CN107213505A (en) * | 2017-07-27 | 2017-09-29 | 南京轩凯生物科技有限公司 | It is a kind of to suppress γ polyglutamic acids and Hyaluronan fibers wound dressing of cicatrization and preparation method thereof |
| GB201720320D0 (en) | 2017-12-06 | 2018-01-17 | Univ Of Sussex | Tissue repair |
| CN109289075B (en) * | 2018-11-08 | 2020-12-11 | 武汉轻工大学 | Preparation method of cellulose-collagen composite nanofiber membrane and wound dressing |
| CN110665065B (en) * | 2019-11-01 | 2021-09-07 | 北京市创伤骨科研究所 | Deferoxamine-loaded artificial periosteum and preparation method thereof |
| CN111330069A (en) * | 2020-03-09 | 2020-06-26 | 蔡钧 | External dressing and preparation method and application thereof |
| CN112741926A (en) * | 2020-12-24 | 2021-05-04 | 西安交通大学 | Polyethylene-vinyl alcohol/gelatin composite electrostatic spinning wound dressing and preparation method thereof |
Citations (4)
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| CN1837274A (en) * | 2005-03-21 | 2006-09-27 | 中国科学院化学研究所 | Degradable and absorbable polymer nano fibrous membrane materials and preparation process and use thereof |
| CN101062426A (en) * | 2006-04-26 | 2007-10-31 | 北京化工大学 | Antibacterial type blended electro spinning nanometer fiber membrane biological dressing and the preparing method thereof |
| CA2423094C (en) * | 2000-09-20 | 2010-06-22 | Richard E. Wooley | Medical compositions, dressings and methods for treating microbial infections of skin lesions |
| CN104511045A (en) * | 2013-09-26 | 2015-04-15 | 五邑大学 | Polyvinyl alcohol/chitosan nano fiber film dressing containing nano silver and preparation thereof |
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| CA2423094C (en) * | 2000-09-20 | 2010-06-22 | Richard E. Wooley | Medical compositions, dressings and methods for treating microbial infections of skin lesions |
| CN1837274A (en) * | 2005-03-21 | 2006-09-27 | 中国科学院化学研究所 | Degradable and absorbable polymer nano fibrous membrane materials and preparation process and use thereof |
| CN101062426A (en) * | 2006-04-26 | 2007-10-31 | 北京化工大学 | Antibacterial type blended electro spinning nanometer fiber membrane biological dressing and the preparing method thereof |
| CN104511045A (en) * | 2013-09-26 | 2015-04-15 | 五邑大学 | Polyvinyl alcohol/chitosan nano fiber film dressing containing nano silver and preparation thereof |
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