CN100577720C - Biodegradable and absorbable polymer nanofiber membrane material and its preparation method and use - Google Patents
Biodegradable and absorbable polymer nanofiber membrane material and its preparation method and use Download PDFInfo
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- CN100577720C CN100577720C CN200510011454A CN200510011454A CN100577720C CN 100577720 C CN100577720 C CN 100577720C CN 200510011454 A CN200510011454 A CN 200510011454A CN 200510011454 A CN200510011454 A CN 200510011454A CN 100577720 C CN100577720 C CN 100577720C
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- Materials For Medical Uses (AREA)
- Nonwoven Fabrics (AREA)
- Spinning Methods And Devices For Manufacturing Artificial Fibers (AREA)
Abstract
本发明属于可生物降解及可生物吸收的聚合物纳米纤维膜领域，特别涉及可生物降解及可生物吸收的聚合物纳米纤维膜材料及其制备方法和医用用途。本发明的可生物降解及可生物吸收高分子纤维膜材料是通过静电纺丝工艺制备出的由直径为几纳米至几百纳米的纤维组成的无纺布材料，其中含有透明质酸是大于0小于等于100重量份，其它高分子材料的量是大于0小于等于100重量份，治疗性药物的量是0～10重量份。本发明的纤维材料具有良好的生物相容性、生物降解性及生物吸收性能，可用于医用组织工程支架材料、人造皮肤、人造血管、创伤敷料、药物输送、生物膜(固定化酶和催化体系的基质)、伤口包敷材料、术后防粘连材料等。The invention belongs to the field of biodegradable and bioabsorbable polymer nanofiber membranes, in particular to a biodegradable and bioabsorbable polymer nanofiber membrane material and its preparation method and medical application. The biodegradable and bioabsorbable polymer fiber membrane material of the present invention is a non-woven fabric material composed of fibers with a diameter of several nanometers to several hundred nanometers prepared by an electrospinning process, wherein the hyaluronic acid content is greater than 0 Less than or equal to 100 parts by weight, the amount of other polymer materials is greater than 0 and less than or equal to 100 parts by weight, and the amount of therapeutic drugs is 0-10 parts by weight. The fiber material of the present invention has good biocompatibility, biodegradability and bioabsorption performance, and can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug delivery, biofilm (immobilized enzyme and catalytic system) matrix), wound dressing materials, postoperative anti-adhesion materials, etc.
Description
Technical field
But the invention belongs to the polymer nanofibre film field of biodegradable and bio-absorbable, but polymer nano fibrous membrane materials of particularly biodegradable and bio-absorbable and preparation method thereof and medical application.
Background technology
Method of electrostatic spinning is a polymeric spray static stretch spinning method, is a kind of preparation polymer superfine fibre technology commonly used.This method is obviously different with traditional spinning processes, at first polymer fluid (inferior strong solution of for example charged polymkeric substance or charged polymer melt) is with several thousand to volt high pressure static electricitys up to ten thousand, charged polymer liquid drops under the effect of electrical forces and is accelerated at conical point capillaceous, when electric field strength is enough big, the polymkeric substance drop can overcome surface tension, form and spray thread, thread drops on the receiving trap of ground connection, forms the polymer fiber film of being made up of ultra-fine fibre of similar non-woven shape.Electrospinning silk technology is at first invented by Zeleny (Phys.Rev.1914.3:69～91), and Formhals (USPatent, 1,975,504.1934) has applied for patent to it.People such as Taylor drive the work of being done on the sputter stream, the basis (Proc.Roy.Soc.Lond.A.1969,31:453～475.) of having established the electrospinning silk at electricity.In in the past 10 years, relevant nearly 60 multinomial patents with the electrostatic spinning process technology and 200 multi-disc research papers are delivered, most of research concentrates on the biologic applications aspect of electro spinning nanometer fiber membrane, and the research of another part concentrates on the basic physical parameters of electrostatic spinning process.The fiber of electrostatic spinning preparation is than thin many of traditional spinning processes, diameter generally tens of to thousands of nanometers, and fiber has vesicular structure; And traditional spining technology comprises that melt-spinning, dry-spinning silk and wet spinning silk are to rely on pressure as the spinning motivating force, and the Fibre diameter that obtains is usually between 10～500 microns.Polymer nanofiber or nanometer non-woven fabric material by the electrostatic spinning technique preparation have great specific surface area and surface-to-volume ratio, fiber surface also can form a lot of micropores simultaneously, therefore very strong adsorptive power and good filterableness, barrier, binding property and heat retaining property etc. are arranged, purposes is arranged very widely, and (Polymer 2001,43 (3): 1025～1029; J.Polym.Sci., Part B:Polym.Phys.2001,39 (21): 2598～2606; AICHE Journal, 1999,45 (1): 190; J.Electrostatics, 1995.35:151～160; Polymer, 1999,40 (16): .4585～4592; Adv.Mater.2000,12 (9): 637～640; Nanotechnology, 1996,7 (3): 216～223; J.Coated Fabrics, 1998.28:63～72; J.Macromol.Sci.-Phys., 1997, B36 (2): 169～173).
The major technique obstacle of making the electrospinning silk fabrics is a preparation speed, a kind of newly-developed, unique multi-port electrospinning silk esJet
TMTechnology can be used for producing the fiber non-woven film that diameter is tens nanometers (PCTInt.Appl. (2002), 55 pp.WO 0292888.; U.S.Pat.Appl.Publ. (2002), 29 pp.US 2002173213; U.S.Pat.Appl.Publ. (2003), US 20030054035; Polymer, 43 (16), 4403～4412 (2002); J.Control.Release, 89,341～353 (2003); Biomacromolecules, 4 (2), 416～423 (2003)).
Surpass more than 100 middle polymers at present and successfully prepare super-fine fiber material by electrospinning, comprising the synthetic biodegradable polymers, as, poly(lactic acid) for example, poly-glycollide, polycaprolactone and multipolymer etc. thereof, natural polymer such as fibroin, scleroproein, collagen protein, chitosan.
Hyaluronic acid (HA) is a kind of natural polymer straight-chain polysaccharide, extensively be present in many soft connective tissues such as intercellular substance, vitreum, umbilical cord, skin, knuckle synovia and rooster comb of humans and animals, has the excellent biological compatibility energy, therefore biological degradation metabolic mechanism and cellular affinity energy are widely used in organizational project.Hyaluronic acid (hyaluronan, HA) and in the past 20 years of derivative become one of important treatment means medically.If prepare the nano fibrous membrane of HA by electrospinning, will further widen the range of application of HA, strengthen its bio-medical function, and to more far-reaching influence is arranged between basic polymkeric substance and the advanced material.But the electrospinning silk of HA report is considerably less, even this mainly is that this makes the electrospinning silk not take place because HA solution also has high viscosity and surface tension under very low concentration.Up to the present, only Ben Chu etc. prepares the nano fibrous membrane (Biomacromol ecular 5:1428～1436 (2004)) of HA by airflow is combined with electrospinning.The introducing of airflow has proposed more requirement to equipment, and improve airflow rate and can increase the suffered pulling force of drop, be a kind of external capillary method of drop that overcomes.
The traditional electrical spinning process require careful consideration a large amount of machined parameters (as the fluid rate of strength of electric field, electrode structure, spinnerette diameters and solution) and control HA solution physical parameter (as soltion viscosity and surface tension), the electrospinning silk of HA solution becomes difficult unusually because of very high viscosity of HA solution and surface tension, especially when the HA molecular weight during very high and strength of solution raising.
Gelatin (GE) is the soluble polypeptide mixture of a kind of hot water, be to get by the collagen hydrolysate in the reticular tissue such as the skin that is present in animal, bone, because it and biological tissue have good affinity, have biodegradable, activated macrophage simultaneously and stop blooding effect, thereby it is medically having extensive must the application: wound dressing, drug conveying, hemostatic material, artificial skin etc.Although gelatin can carry out electrostatic spinning (Polymer, 2004,45:5361～5368) in 2,2,2 tfifluoroethyl alcohol solution, the aqueous solution of gelatin is considered to be not suitable for carry out electrospinning silk (Polymer, 2004,45:5361～5368; J Biol Chem, 1934,107:629～634).
Summary of the invention
The polymer nano fibrous membrane materials that one of purpose of the present invention provides the biodegradable of different degree of crosslinking that a kind of method by chemically crosslinked obtains and absorbs.
Two of purpose of the present invention is to have high soltion viscosity and surface tension makes it be difficult to carry out electrostatic spinning under very low concentration at the HA aqueous solution, provides a kind of method of electrostatic spinning to prepare the method for the polymer nano fibrous membrane materials of HA based, biodegradable and absorption.
Three of purpose of the present invention provides the preparation method of the polymer nano fibrous membrane materials with good physical mechanical property.
Four of purpose of the present invention provides the preparation method of the HA/GE composite fiber membrane material with good cell adhesion performance.
Five of purpose of the present invention is the improvement by processing parameter, and the processing parameter of the aqueous solution electrostatic spinning of the processing parameter of polymer aqueous solution electrostatic spinning, particularly gelatin is provided.
Six of purpose of the present invention provides a kind of bio-medical purposes of the biodegradable and polymer nano fibrous membrane materials that absorbs.
Seven of purpose of the present invention provides the polymer fiber preparation method of film material that contains curative drug.
The present invention is based on the research background of prior art, under very low concentration, has high soltion viscosity and surface tension makes it be difficult to carry out electrostatic spinning at HA solution, the wetting ability and the polyanionic surface of HA molecule make the negatively charged ion cell be difficult to stick simultaneously, when keeping the HA biological nature, adjusting by the electrostatic spinning process parameter, it is compound that HA and other are had a low-molecular-weight polymer (for example gelatin, PEO, PVA), regulate the viscosity and the fluid characteristics of HA based sols, make the HA based sols more help the electrospinning silk; Other degradable high molecular introducing simultaneously can change the hydrophilicity and hydrophobicity of HA itself, thereby has prolonged the interior residence time of body of material, and the introducing of gelatin also can be given the filamentary material protein properties, improves the cell adhesion performance of HA sill; Prepare the nano-composite fiber film of HA base by electrospinning silk technology, prepare the HA based nano-fiber mould material of different degree of crosslinking then by the method for chemically crosslinked.
Containing hyaluronic amount in the biodegradable and polymer nano fibrous membrane materials that absorbs of the present invention is smaller or equal to 100 weight parts greater than 0, the amount of other macromolecular material is greater than 0 smaller or equal to 100 weight parts, and the amount of curative drug is 0～10 weight part.
It is the fibrous fiber film materials of several nanometers to the hundreds of nanometer that the mixing solutions that will contain hyaluronic acid, other macromolecular material, curative drug is prepared by diameter by electrostatic spinning process.The adding of other high score material can improve the hydrodynamic performance of hyaluronic acid solution, give filamentary material other characteristic simultaneously: for example adding of gelatin, not only improved the fluid property of hyaluronic acid solution good, and give the material protein properties, make filamentary material have better cell adhesion performance.Filamentary material of the present invention has excellent biological compatibility, biological degradability and bio-absorbable performance, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film (matrix of immobilized enzyme and catalyst system), wound coated material, post-operation adhesion preventing material etc.
But described polymer nano fibrous membrane materials biodegradable and bio-absorbable is mainly hyaluronic acid, and described other macromolecular material is selected from polyvinyl alcohol (PVA), polyoxyethylene glycol, polyoxy ethane (PEO), polylactide (PLLA), poly-glycollide (PGA), the multipolymer of glycollide and rac-Lactide (P (GA-co-LA)), polycaprolactone (PCL), poly-to two evil ketone, starch, cellulose ethanoate, collagen, gelatin, Fibrinogen, fibronectin in serum, fibroin, the peptide polymer of elastin mimicry, enzyme-lipase, nucleic acid, dextran, sodium alginate, chitosan and their any multipolymer or mixture.
Polymer nano fibrous membrane materials preparation method biodegradable and that absorb of the present invention follows these steps to carry out:
(1) preparation of macromolecular solution
Hyaluronic acid and other macromolecular material are dissolved in the solvent by a certain percentage, obtain the macromolecule mixture solution of homogeneous transparent in 40～60 degree dissolvings.Wherein the percentage concentration of macromolecule mixture solution is 1～50wt/v, and solvent is the mixing solutions of water and ethanol or acetone, and the volume ratio of ethanol or acetone and water is 0～50: 100.The adding of ethanol or acetone solvent helps spraying the volatilization of solvent in the process, thereby avoids the adhesion of fiber.Add curative drug then in above-mentioned macromolecule mixture solution, the weight ratio of curative drug and above-mentioned macromolecule mixture is 0～20: 100.
Described hyaluronic molecular weight is 150～3,000,000.
Described other polymer is selected from polyvinyl alcohol (PVA), polyoxy ethane (PEO), polylactide (PLLA), poly-glycollide (PGA), the copolymer p of glycollide and rac-Lactide (GA-co-LA), polycaprolactone (PCL), poly-to two evil ketone, starch, cellulose ethanoate, collagen, Fibrinogen, fibronectin in serum, fibroin, the peptide polymer of elastin mimicry, gelatin, dextran, sodium alginate, chitosan, enzyme-lipase, nucleic acid and their any multipolymer or mixture.
Described other high molecular molecular weight is 5～500,000.
Contain hyaluronic amount in the macromolecule mixture solution and be greater than 0 smaller or equal to 100 weight parts, the amount of other macromolecular material is greater than 0 smaller or equal to 100 weight parts, and the amount of curative drug is 0～10 weight part.
The percentage concentration of described macromolecule mixture is 1～50w/v.
Described curative drug is selected from AgCl, TiO
2, thyrocalcitonin, a kind of in Regular Insulin, nerve growth factor, Sphingolipids,sialo, hydrocortisone (hudrocortisone), the control growing factor, steroid, antibiotics, pain relieving class, anti-inflammatory type, anesthesia class, expelling parasite class, anticoagulation class, mycobacteria, the antiviral class.
The electrospinning silk prepares nano fibrous membrane
Electrostatic spinning process is: with the mixture solution that contains hyaluronic acid and other macromolecular material of step (1), or with the hyaluronic acid that contains of step (1), the mixing solutions of other macromolecular material and curative drug is packed in the homothermic device for storing liquid, the piston of device for storing liquid links to each other with syringe pump, device for storing liquid links to each other with spinning nozzle by four fluorine tube, distance between the collector of adjustment spinning nozzle and ground connection, regulate the gas flow rate of envrionment temperature and environment, open high-voltage power supply, open syringe pump, injection stream is mapped to certain temperature and rotation or speed of rotation, or on the collector of certain translational speed, obtain polymer nano fibrous membrane materials.In the electrostatic spinning process, the thickness of the stability of many parameter influence electrostatic spinning processes, continuity, fiber and uniformity coefficient etc., for example rotating speed of the translational speed of the gas flow rates of polymericular weight, strength of solution, solvent, fluidic electric density, envrionment temperature, environment, static voltage, shower nozzle, collector or translational speed etc.
The inventor thinks in the natural polymer water solution systems such as HA, gelatin, there is strong interaction between the molecular chain,, makes that molecule is rigidity in the HA and the GE aqueous solution just because of strong interactional existence, even form immobilising gel, therefore even be considered to can not electrostatic spinning.The present invention improves the temperature of spinning solution by the envrionment temperature in the raising spinning process, thereby destruction hydrogen bond, improve the fluid viscosity and the surface tension of solution, promote the volatilization of solvent in the spray silk process, reduce the viscosity and the surface tension of HA solution by adding low-molecular-weight polymkeric substance simultaneously, or, realize the electrostatic spinning of the natural polymer aqueous solution such as HA, gelatin by improving the spinning property that concentration improves aqueous gelatin solution.
Electrostatic spinning for polymers soln prepares polymer nano fibrous membrane materials, and technical parameter mainly can be controlled in following experiment condition scope by the present invention:
A) feeding rate of solution is 5～300ul/min, and preferred value is 20～150ul/min;
B) envrionment temperature is 30～80 ℃, and preferred temperature is 40～60 ℃;
C) air velocity of environment is 0～8.5m
3/ hr, preferred value is 0.5～5m
3/ hr;
D) static voltage is 1～60kV, and suitable value is 15～50kV;
E) distance between spinning nozzle and the collector is 5～25cm, and preferred value is 7～20cm;
F) translational speed of spinning nozzle is 0～5m/min;
G) rotation of collector or speed of rotation are 0～2400r/min, or the translational speed of collector is 0～10m/nin;
H) temperature range of collector is 30～80 ℃, and optimal temperature is 40～70 ℃;
I) temperature of reservoir is 30～80 ℃.
Described electrospinning silk process equipment used is to utilize existing electrospinning silk equipment, mainly form by high-voltage power supply, feeding device, jet apparatus, collection device four parts, high-voltage power supply can adopt single high-voltage power supply or two high-voltage power supply system, and feeding device adopts the pumping feed; Jet apparatus can adopt the form of single spinning nozzle or many spinning nozzle, and spinning nozzle is installed on the mobile platform; The collection device part can adopt various forms of collectors such as rotating-disk, flat board, cylinder, can carry out temperature control and control speed to collector.
In preparation method of the present invention,, can be used for preparing the polymer nanofibre film that fibre orientation is arranged when the collector rotating speed is higher than 1500r/min; When the collector rotating speed is lower than 1500r/min, be used to prepare the polymer nanofibre film of fiber lack of alignment.
The vacuum-drying 2 days in 40～60 ℃ of vacuum drying ovens of prepared polymer nano fibrous membrane materials.
(3) method of chemically crosslinked provides the polymer nano fibrous membrane materials of different degree of crosslinking
The polymer nano fibrous membrane materials that step (2) is obtained places the mixing solutions of ethanol/water, the linking agent that adds metering, crosslinked 10～48 hours in 0～40 ℃, wash away vacuum-drying 2 days in 40～60 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.Wherein the weight of the mixing solutions of polymer nano fibrous membrane materials and ethanol/water and volume ratio are 1: 20～2000 (as g/ml), and the volume ratio of ethanol and water is 80～100: 0～20, and linking agent concentration in mixing solutions is 1～30mmol/L.
Described linking agent is selected from carbodiimide, glutaraldehyde, formaldehyde, diepoxides or divinylsulfone etc.Polymer fiber mould material of the present invention can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film (matrix of immobilized enzyme and catalyst system), wound coated material, post-operation adhesion preventing material etc.
Polymer fiber preparation method of film material of the present invention has following characteristics:
1. the invention provides the method that a kind of method of electrostatic spinning prepares the polymer nano fibrous membrane materials of HA based, biodegradable and absorption.
2. the invention provides and have that homogeneity is good, porosity is high, the method for the medical polymer based nano-fiber mould material of good biocompatibility.
3. the present invention is by regulating the shape of processing parameter and collector, the shape of diameter, orientation, arrangement and support that can controlling fiber etc.
4. the invention provides the method that preparation contains the polymer-based nano fiber film material of curative drug.
5. the invention provides the material of Fibre diameter, have broad application prospects at 3nm～900nm.
Description of drawings
Fig. 1. the SEM figure of the polymer nanofibre film of the embodiment of the invention 2 preparations.
Fig. 2. the SEM figure of the polymer nanofibre film of the embodiment of the invention 3 preparations.
The SEM figure of the polymer nanofibre film of Fig. 3 embodiment of the invention 5 preparations.
The SEM figure of the polymer nanofibre film of Fig. 4 embodiment of the invention 7 preparations.
The SEM figure of the polymer nanofibre film of Fig. 5 embodiment of the invention 9 preparations.
Embodiment
Embodiment 1.
1) preparation quality concentration expressed in percentage by volume is water/ethanolic soln 5ml of the HA/GE of 1.8wt/v, and wherein the HA/GE mass ratio is 5: 1, and water/alcoholic acid volume ratio is 90: 10, places device for storing liquid.
2) metal plate is installed as collector, the temperature of collector is 40 degree.
3) distance of regulating between spinning nozzle and the collecting board is 8cm.
4) envrionment temperature of spinning is 50 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collecting board are 50 degree.
5) open high-voltage power supply, regulating voltage is to 18KV, and the air velocity of environment is 6m
3/ hr, the delivery rate of solution is 100ul/min, carries out spinning, then the polymer fiber film on the dash receiver is spent vacuum-dryings 2 days in 40.
6) the polymer fiber film of vacuum-drying being placed 20ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the carbodiimide of 10mmol/L, spend crosslinked 12 hours in 30, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/GE nano fibrous membrane of gained, average fibre diameter is 20～300 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Embodiment 2
1) preparation quality concentration expressed in percentage by volume is water/ethanolic soln 10ml of the HA/GE of 2wt/v, and wherein the HA/GE mass ratio is 3: 1, and water/alcoholic acid volume ratio is 90: 10, contains the somatomedin of 0.02 gram in the polymers soln, and polymers soln is placed device for storing liquid.
2) metal plate is installed as collector.
3) distance of regulating between spinning nozzle and the collecting board is 8cm.
4) envrionment temperature of spinning is 50 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collecting board are 50 degree.
5) open high-voltage power supply, regulating voltage is to 18KV, and the air velocity of environment is 5m
3/ hr, the translational speed of spinning nozzle is 0.1m/min, and the delivery rate of solution is 120ul/min, carries out spinning, and the translational speed of collecting board is 0.01m/min, then the polymer fiber film on the dash receiver is spent vacuum-dryings 2 days in 40.
6) the polymer fiber film of vacuum-drying being placed 50ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the carbodiimide of 10mmol/L, spend crosslinked 12 hours in 30, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/GE nano fibrous membrane of gained, average fibre diameter is 20～300 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Embodiment 3
1) preparation quality concentration expressed in percentage by volume is water/ethanolic soln 5ml of the HA/GE of 3wt/v, and wherein the HA/GE mass ratio is 1: 1, and water/alcoholic acid volume ratio is 90: 10, places device for storing liquid.
2) metal drum is installed as collector.
3) distance of regulating between spinning nozzle and the collector is 8cm.
4) envrionment temperature of spinning is 50 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collecting board are 50 degree.
5) open high-voltage power supply, regulating voltage is to 18KV, and the air velocity of environment is 4m
3/ hr, the delivery rate of solution is 130ul/min, and the translational speed of spinning nozzle is 0.5m/min, and the rotating speed of collector is 300r/min, carries out spinning, and the polymer fiber film that will receive then on the drum is spent vacuum-dryings 2 days in 40.
6) the polymer fiber film of vacuum-drying being placed 30ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the carbodiimide of 10mmol/L, spend crosslinked 12 hours in 37, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/GE nano fibrous membrane of gained, average fibre diameter is 20～500 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Embodiment 4
1) preparation quality concentration expressed in percentage by volume is the water/ethanolic soln 200ml of the HA/ dextran of 5wt/v, and wherein HA/ dextran mass ratio is 2: 1, and water/alcoholic acid volume ratio is 90: 10, places device for storing liquid.
2) metal plate is installed as collector.
3) distance of regulating between spinning nozzle and the collecting board is 10cm, and spinning nozzle is a double-spinneret, and the distance between two spinning nozzle is 5cm.
4) envrionment temperature of spinning is 50 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collecting board are 50 degree.
5) open high-voltage power supply, regulating voltage is to 22KV, and the delivery rate of solution is 130ul/min, and the translational speed of spinning nozzle is 0.05m/min, and the air velocity that carries out the spinning environment is 4m
3/ hr carries out spinning, and the translational speed of collecting board is 0.2m/min, then the polymer fiber film on the dash receiver is spent vacuum-dryings 2 days in 40.
6) the polymer fiber film of vacuum-drying being placed 2000ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the glutaraldehyde of 10mmol/L, spend crosslinked 48 hours in 37, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/ dextran nano fibrous membrane of gained, average fibre diameter is 20～200 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Embodiment 5
1) preparation quality concentration expressed in percentage by volume is water/ethanolic soln 10ml of the HA/GE of 5wt/v, and wherein the HA/GE mass ratio is 1: 10, and water/alcoholic acid volume ratio is 90: 10, places device for storing liquid.
2) metal plate is installed as collector.
3) distance of regulating between spinning nozzle and the collecting board is 10cm.
4) envrionment temperature of spinning is 70 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collecting board are 70 degree.
5) open high-voltage power supply, regulating voltage is to 22KV, and the air velocity of environment is 4m
3/ hr, the delivery rate of solution is 190ul/min, carries out spinning, non-woven fabrics 40 degree vacuum-dryings 2 days.
6) the polymer fiber film of vacuum-drying being placed 80ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the glutaraldehyde of 10mmol/L, spend crosslinked 48 hours in 37, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/GE nano fibrous membrane of gained, average fibre diameter is 20～150 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Embodiment 6
1) preparation quality concentration expressed in percentage by volume is water/ethanolic soln 10ml of the HA/PEO of 3wt/v, wherein the HA/PEO mass ratio is 3: 1, water/alcoholic acid volume ratio is 90: 10, contains the Asprin of 0.02 gram in the polymers soln, and above-mentioned polymers soln is placed device for storing liquid.
2) metal drum is installed as collector.
3) distance of regulating between spinning nozzle and the collecting board is 12cm.
4) envrionment temperature of spinning is 60 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collector are 60 degree.
5) open high-voltage power supply, regulating voltage is to 22KV, and the air velocity of environment is 5m
3/ hr, the delivery rate of solution is 150ul/min, the rotating speed of collector is 300r/min, carries out spinning, non-woven fabrics 40 degree vacuum-dryings 2 days.
6) the polymer fiber film of vacuum-drying being placed 80ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the carbodiimide of 10mmol/L, spend crosslinked 48 hours in 3, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/PEO nano fibrous membrane of gained, average fibre diameter is 20～300 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Embodiment 7
1) preparation quality concentration expressed in percentage by volume is water/ethanolic soln 5ml of the HA/PEO of 3wt/v, wherein the HA/PEO mass ratio is 1: 1, water/alcoholic acid volume ratio is 90: 10, contains the norfloxicin of 0.01 gram and the NaCl of 0.006 gram in the polymers soln, places device for storing liquid.
2) metal plate is installed as collector.
3) distance of regulating between spinning nozzle and the collecting board is 12cm.
4) envrionment temperature of spinning is 60 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collecting board are 60 degree.
5) open high-voltage power supply, regulating voltage is to 22KV, and the delivery rate of solution is 130ul/min, and the air velocity of environment is 5m
3/ hr carries out spinning, and 40 degree vacuum-dryings obtained the polymer fiber film in 2 days then.
6) the polymer fiber film of vacuum-drying being placed 80ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the carbodiimide of 10mmol/L, spend crosslinked 48 hours in 37, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/PEO nano fibrous membrane of gained, average fibre diameter is 20～150 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Embodiment 8
1) preparation quality concentration expressed in percentage by volume is water/ethanolic soln 5ml of the HA/PVA of 3wt/v, and wherein the HA/PVA mass ratio is 1: 1, and water/alcoholic acid volume ratio is 90: 10, contains the somatomedin of 0.01 gram in the polymers soln, places device for storing liquid.
2) metal drum is installed as collector.
3) distance between joint spinning nozzle and the collector is 12cm.
4) envrionment temperature of spinning is 60 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collector are 60 degree.
5) open high-voltage power supply, regulating voltage is to 22KV, and the delivery rate of solution is 160ul/min, and the air velocity of environment is 5m
3/ hr, the rotating speed of collector are 1500r/min, carry out spinning, non-woven fabrics 40 degree vacuum-dryings 2 days.
6) the polymer fiber film of vacuum-drying being placed 80ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the carbodiimide of 10mmol/L, spend crosslinked 48 hours in 37, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/PVA nano fibrous membrane fibre orientation of gained is arranged, average fibre diameter is 100～900 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Embodiment 9
1) preparation quality concentration expressed in percentage by volume is water/ethanolic soln 10ml of the HA/GE of 4.65wt/v, and wherein the HA/GE mass ratio is 1: 30, and water/alcoholic acid volume ratio is 90: 10, contains the somatomedin of 0.01g in the solution, and solution is placed device for storing liquid.
2) metal drum is installed as collector.
3) distance between joint spinning nozzle and the collecting board is 12cm.
4) envrionment temperature of spinning is 60 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collector are 60 degree.
5) open high-voltage power supply, regulating voltage is to 22KV, and the delivery rate of solution is 130ul/min, and the air velocity of environment is 5m
3/ hr, the translational speed of spinning nozzle is 0.3m/min, the rotating speed of collector is 600r/min, carries out spinning, non-woven fabrics 40 degree vacuum-dryings 2 days.
6) the polymer fiber film of vacuum-drying being placed 100ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the carbodiimide of 15mmol/L, spend crosslinked 24 hours in 25, wash away fully with the linking agent of a large amount of deionized water wash then until remnants, vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then, the HA/GE nano fibrous membrane of gained, average fibre diameter is 20～200 nanometers, can be used for the medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, the wound coated material, post-operation adhesion preventing material etc.
Embodiment 10
1) preparation quality concentration expressed in percentage by volume is the aqueous solution 5ml of the HA/ sodium alginate of 3wt/v, and wherein HA/ sodium alginate mass ratio is 1: 1, places device for storing liquid.
2) metal drum is installed as collector.
3) distance between spinning nozzle and the collecting board is 8cm.
4) Si envrionment temperature is 50 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collector are 50 degree.
5) open high-voltage power supply, regulating voltage is to 18KV, and the delivery rate of solution is 130ul/min, and the air velocity of environment is 3m
3/ hr, the translational speed of spinning nozzle is 0.3m/min, the rotating speed of collector is 300r/min, carries out spinning, non-woven fabrics 40 degree vacuum-dryings 2 days.
6) the polymer fiber film of vacuum-drying being placed 20ml concentration is the mixing solutions (volume ratio of ethanol and water is 90: 10) of ethanol water of the carbodiimide of 15mmol/L, spend crosslinked 24 hours in 25, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/ sodium alginate nano fiber film of gained, average fibre diameter is 100～200 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Embodiment 11
1) preparation quality concentration expressed in percentage by volume is the water/ethanolic soln 5ml of the HA/ polyoxyethylene glycol of 4wt/v, and wherein HA/ polyoxyethylene glycol mass ratio is 1: 1, and water/alcoholic acid volume ratio is 90: 10, contains the norfloxicin of 0.01 gram in the polymers soln, places device for storing liquid.
2) two metal plates are installed as collector, the distance between the metal sheet is 5cm.
3) distance of regulating between spinning nozzle and the collecting board is 12cm.
4) envrionment temperature of spinning is 50 degree, comprises that the temperature of solution in the device for storing liquid and the temperature of collecting board are 50 degree.
5) open high-voltage power supply, regulating voltage is to 22KV, and the translational speed of spinning nozzle is 0.01m/min, and the delivery rate of carrying out spinning solution is 130ul/min, and the air velocity of environment is 5m
3/ hr carries out spinning, and the translational speed of collecting board is 0.3m/min, and 40 degree vacuum-dryings obtained fibre orientation arranged polymeric tunica fibrosa in 2 days then.
6) the polymer fiber film of vacuum-drying being placed 80ml concentration is the mixing solutions (volume ratio of acetone and water is 90: 10) of acetone water of the glutaraldehyde of 10mmol/L, spend crosslinked 48 hours in 37, wash away vacuum-drying 2 days in 40 ℃ of vacuum drying ovens then then fully with the linking agent of a large amount of deionized water wash until remnants.The HA/ polyoxyethylene glycol nano fibrous membrane of gained, average fibre diameter is 20～150 nanometers, can be used for medical tissue engineering scaffold material, artificial skin, artificial blood vessel, wound dressing, drug conveying, microbial film, wound coated material, post-operation adhesion preventing material etc.
Claims (8)
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