CN110433325A - A kind of protide high polymer nanometer fiber hemostatic material and its preparation method and application - Google Patents

A kind of protide high polymer nanometer fiber hemostatic material and its preparation method and application Download PDF

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Publication number
CN110433325A
CN110433325A CN201910680967.1A CN201910680967A CN110433325A CN 110433325 A CN110433325 A CN 110433325A CN 201910680967 A CN201910680967 A CN 201910680967A CN 110433325 A CN110433325 A CN 110433325A
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protide
hemostatic material
high polymer
nanometer fiber
spinning
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卢伟鹏
郭燕川
祝文威
穆瑞赓
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Hangzhou Zhongke Runde Biotechnology Development Co Ltd
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Hangzhou Zhongke Runde Biotechnology Development Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001Use of materials characterised by their function or physical properties
    • A61L24/0042Materials resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10Polypeptides; Proteins
    • A61L24/102Collagen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10Polypeptides; Proteins
    • A61L24/104Gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10Polypeptides; Proteins
    • A61L24/106Fibrin; Fibrinogen
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01FCHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F4/00Monocomponent artificial filaments or the like of proteins; Manufacture thereof
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01FCHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F4/00Monocomponent artificial filaments or the like of proteins; Manufacture thereof
    • D01F4/02Monocomponent artificial filaments or the like of proteins; Manufacture thereof from fibroin
    • DTEXTILES; PAPER
    • D06TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
    • D06MTREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
    • D06M10/00Physical treatment of fibres, threads, yarns, fabrics, or fibrous goods made from such materials, e.g. ultrasonic, corona discharge, irradiation, electric currents, or magnetic fields; Physical treatment combined with treatment with chemical compounds or elements
    • DTEXTILES; PAPER
    • D06TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
    • D06MTREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
    • D06M10/00Physical treatment of fibres, threads, yarns, fabrics, or fibrous goods made from such materials, e.g. ultrasonic, corona discharge, irradiation, electric currents, or magnetic fields; Physical treatment combined with treatment with chemical compounds or elements
    • D06M10/001Treatment with visible light, infrared or ultraviolet, X-rays
    • DTEXTILES; PAPER
    • D06TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
    • D06MTREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
    • D06M10/00Physical treatment of fibres, threads, yarns, fabrics, or fibrous goods made from such materials, e.g. ultrasonic, corona discharge, irradiation, electric currents, or magnetic fields; Physical treatment combined with treatment with chemical compounds or elements
    • D06M10/02Physical treatment of fibres, threads, yarns, fabrics, or fibrous goods made from such materials, e.g. ultrasonic, corona discharge, irradiation, electric currents, or magnetic fields; Physical treatment combined with treatment with chemical compounds or elements ultrasonic or sonic; Corona discharge
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/04Materials for stopping bleeding
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/12Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • DTEXTILES; PAPER
    • D06TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
    • D06MTREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
    • D06M2101/00Chemical constitution of the fibres, threads, yarns, fabrics or fibrous goods made from such materials, to be treated
    • D06M2101/02Natural fibres, other than mineral fibres
    • D06M2101/10Animal fibres
    • DTEXTILES; PAPER
    • D06TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
    • D06MTREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
    • D06M2101/00Chemical constitution of the fibres, threads, yarns, fabrics or fibrous goods made from such materials, to be treated
    • D06M2101/02Natural fibres, other than mineral fibres
    • D06M2101/10Animal fibres
    • D06M2101/14Collagen fibres

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Abstract

The invention discloses a kind of protide high polymer nanometer fiber hemostatic materials and its preparation method and application, and protide macromolecule dissolution is configured to spinning solution;Protide macromolecule is prepared by electrostatic spinning the nanofiber of tridimensional network;The nanofiber of tridimensional network is polarised in polarized electric field;The nanofiber of tridimensional network after polarization process is dried and sterilizes, and obtains protide high polymer nanometer fiber hemostatic material.The present invention obtains material, and there is special structure can effectively activate coagulation factor, improves the haemostatic effect of unit volume fibrous material, reduces the infection probability of wound location.This material has good biocompatibility and biodegradability, can be used as a kind of hemostatic material.

Description

A kind of protide high polymer nanometer fiber hemostatic material and its preparation method and application
Technical field
The present invention relates to nanofiber manufacturing field, specially a kind of protide high polymer nanometer fiber hemostatic material and its Preparation method and application.
Background technique
Traditional hemostatic material (such as cotton yarn, bandage, tourniquet) is existing for irregular shape, deep, narrow, arteriorrhexis etc. The haemostatic effect of the common wound in field is very unsatisfactory.Inorganic mineral such as zeolite hemostatic material is difficult to use under windy environment, and It may cause third-degree burn, or even residual vascular and lung lead to thrombus.ɑ-cyanoacrylate hemostatic material degradation process In then inevitably release the noxious materials such as a small amount of cyanogen and formaldehyde, cause tissue inflammation.With the development of science and technology, people by Gradually center of gravity is transferred in novel bioabsorbable polymer material exploitation.Natural protide high molecular material (such as collagen, gelatin, Fibroin etc.) there is good biocompatibility and degradability, it is the emphasis of researchers' concern.Collagen electrospinning film has Porosity is high, and the good advantage of water absorbing properties, can be used for clinical hemostasis material, (such as Cheng Weilu, Li Hui, He Jinmei are degradable compound The preparation of hemostasis collagen protein sponge and biologic applications performance study [J] chemistry and bonding, 2016,38 (4): 231-234).In (He Meizhen, Chen little Yan, Zheng Jingjing gelfoam are surveyed in the invasive artery of ICU for point of puncture application after the invasive artery of ICU surveys pressed pipe Application [J] after pressed pipe in point of puncture hemostasis nurses journal .2015 (22): embodiment of 40-41.) and in tooth extraction wound stopping blooding (Zhu Shaoping, Zhang Aiping sponeostan tooth extraction wound 290 effect observation [J] Shandong medicine .2003 (35) of hemostasis: 69- 69.) in, the simple of gelfoam hemostasis, economy and validity have obtained the approval of patient and medical staff.Sorada etc. (Sorada K,Siriporn D,Juthamas R.Aninnovative bi-layered wound dressing made of silk and gelatin for accelerated woundhealing.International Journal of Pharmaceutics, 2012,436:141-153.) research fibroin albumen and gelatin bilayer hemostatic material and it is commercial only Blood material promotes wound healing compared to that can significantly reduce wound area.However it is higher and higher to hemostatic material in medical field Under performance requirement, the hemostatic material of protide still has that anthemorrhagic speed is slow, to the drawing ability and surface of a wound group of blood constituent The shortcoming of poor adhesive force is knitted, therefore how to improve the anthemorrhagic speed of protide macromolecule hemostatic material, is allowed to when contacting wound Coagulation factor can be quickly activated, the generation of fibrin ferment is accelerated, promoting the formation of sludged blood is the pass for opening up such material application Key.
Some researches show that the surface charge of material can influence the selective absorption and sedimentation of albumen, promote blood coagulation system Activation, the especially material with negative charged surface can be activated solidifying in blood coagulation system by its surface charge abundant Blood factor Ⅻ, and the factor be cause one of key factor of intrinsic coagulation system starting (OstomelTA, ShiQ, Stoimenov PK,et al.Metal oxide surface charge mediated hemostasis.Langmuir.2007,23:11233-11238;Shariat-MadarZ,Mahdi F,Schmaier AH.Assembly and activation of the Plasmakallikrein/kininsystem:a new interpretation.International Immunopharmaeol.2002,2(13-14):1841-1849).Chen Lu etc. Studies have shown that its anthemorrhagic performance of methylated collagen positively charged by surface modification be greatly improved (Chen Lu, Li Xia, Jiang Bo modify styptic activity research [J] China and foreign countries medical treatment .2013,32 (23): 130-131 of collagen).Protein is most Important biology polarization high molecular material, has the ability (summer that can be stored real charge for a long time and (or) keep polarized state Zhong Fu Biomaterials of Electret [J] material Leader .1994 (1): 48-52.).Under the action of high voltage electric field, carboxyl, amino Equal charged groups tend to orderly polarization offset, and fetter the charge intensified in a large amount of electric fields, and fiber surface is made to form difference Potential areas.Electrostatic spinning is a kind of nanofiber technology of preparing of simple process, relative to sponge hemostatic material, nanofiber The material specific surface area of structure is bigger, more with the contact area of blood, and hemostatic composition is easier to adhesion and aggregation in fiber surface, from And shorten bleeding stopping period, raising haemostatic effect (preparation of Liu Xuefeng wound hemostasis nano-fiber material and the Nanjing performance [D]: Southeast China University, 2011:1-51).The polarization process of the presence of high-voltage electrostatic field and tunica fibrosa later what is more is also polarity material Material provides polarization and captures charge offer may.
Protide high molecular material constructs a kind of molecular chain orientation arrangement by electrostatic spinning technique, and fiber surface distribution is more The nano-fiber material of the three-dimensional microcosmic network structure of kind hydrophilic radical, then by polarization process, make material internal polarization orientation, Surface is distributed polarization charge, so that absorption moisture that can be instantaneous in wound hemostasis, adsorbs blood constituent, increase in subrange Fluid viscosity is healed, and quickly activates coagulation factor, accelerates the generation of fibrin ferment, promotes coagulation process, to improve material Anthemorrhagic speed.Therefore the protide biological absorbable hemostatic material of this kind of energy quick-acting haemostatic powder is in terms of clinical medicine and hemostasis There to be more significant advantage.
Summary of the invention
The infection risk that the purpose of the present invention is may cause for protide macromolecule hemostatic material, provides a kind of raising The preparation method of the nanofiber hemostatic material of unit volume haemostatic effect.
Another object of the present invention is to provide a kind of protide high polymer nanometer fiber hemostatic materials.
In order to solve the above-mentioned technical problem, the technical scheme adopted by the invention is that:
A kind of preparation method of protide high polymer nanometer fiber hemostatic material, includes the following steps:
(1) protide macromolecule dissolution is configured to spinning solution;
(2) protide macromolecule is prepared by electrostatic spinning the nanofiber of tridimensional network;
(3) nanofiber of tridimensional network is polarised in polarized electric field;
(4) nanofiber of the tridimensional network after polarization process is dried and sterilizes, and obtains protide macromolecule Nanofiber hemostatic material.
The method of the electrostatic spinning is, using single or mixed liquor as solvent, using protide macromolecule as solute, adjusts Spinning parameter, be prepared molecular chain orientation arrangement, fiber surface be distributed a variety of hydrophilic radicals with three-dimensional net structure Nano-fiber material.
The solvent is water, formic acid, acetic acid, propionic acid, trifluoroethanol, hexafluoroisopropanol, Hexafluoro acetone, dimethyl formyl What one of amine, dimethyl acetamide, acetone, ketone, butanone, cyclohexanone, ethyl alcohol, methanol or more than one solvents formed Mixed solvent;
The protide macromolecule is collagen, gelatin, fibroin albumen, spider silk fibroin, elastin laminin, the molten egg of corn alcohol One or more than one kinds of compositions in white, polypeptide;Concentration of dope is between 2%~40%.
The spinning parameter, including concentration of dope is between 2%~40%, spinning voltage is between 5~90kV, spinning Flight lead between 5~30cm, spinning solution temperature is at 0~70 DEG C, 0~65 DEG C of environment temperature.
Electrostatic spinning mode includes spininess spinning, spiral textile, metal silk spinning, sheet metal spinning and metal salient point spinning etc..
Polarization process described in step (3), refers in polarized electric field, and electrospinning protide fibrous inside forms polarization charge Or dipole, carboxyl and the orderly polarization offset of amino charged group, and the charge intensified in a large amount of electric fields is adsorbed, it is formed in fiber Space bound charge.
The polarization mode includes corona polarizing, thermal poling, the polarization of soft X-ray, radiation-polarizing and magnetic polarization.
Step (4) described drying, is dried in a vacuum drying oven, and at 35-80 DEG C, drying time is no more than drying temperature 48h。
The sterilizing, including ethylene oxide sterilizing, ultraviolet sterilization or radiosterilization.
Present invention protide high polymer nanometer fiber hemostatic material obtained be by fibre diameter between 0.05~5 μm Micro nanometer fiber composition, with high voidage and specific surface area three-dimensional network laminated structure.As hemostatic material
Heterogeneous (coarse) nanofiber three-dimensional structure material, can effectively improve hydrophilic absorbent;Band heterogeneous The carboxyl of ammeter face and fiber surface, which reacts bring with sodium ion, stimulates the coagulation factor that can effectively activate in blood coagulation system, The generation for promoting fibrin ferment, to accelerate coagulation process.The present invention is constructed a kind of with special construction by electrostatic spinning process With the nanofiber hemostatic material of the three-dimensional net structure of function.This fibrous material, since the strength of electrostatic force is drawn when electrospinning It stretches, molecular chain orientation arrangement, pulp freeness is big, the group of surface integrated distribution multiple functions;Due to orientation when polarization And compact arranged molecular structure, anisotropy is big, is easier to that gelatin chains is made to form polarization charge or dipole, carboxyl and ammonia The charged groups such as base can also tend to orderly polarization offset, and adsorb the charge intensified in a large amount of electric fields, become intrastitial sky Between bound charge, thus formed nanofiber composition non-homogeneous charged surface, to a certain extent activate blood coagulation system in Coagulation factor, promote the generation of fibrin ferment, to accelerate coagulation process, achieve the purpose that quick-acting haemostatic powder.
Compared with prior art, the beneficial effects of the present invention are:
The present invention controls the microstructure of fiber by regulation electrospinning parameters, while arranging molecular chain orientation more More polar groups (such as carboxyl) is exposed in fiber surface, and carboxyl is reacted with sodium ion can stimulate activation coagulation factor.Later Polarization process, so that fibrous inside and surface is obtained polarization orientation and capture space charge, be made of to obtain nanofiber Non-homogeneous charged surface.This special structure can effectively activate coagulation factor, improve stopping for unit volume fibrous material Blood effect reduces the infection probability of wound location.This material has good biocompatibility and biodegradability, can be with As a kind of Absorbable hemostatic material.
Detailed description of the invention
The following drawings is a part of the application, is to further elucidate to of the invention, but do not constitute to limit of the invention It is fixed, in which:
Fig. 1 is the preparation facilities schematic diagram in embodiment 2;
Fig. 2 is that the hemostatic material fibre structure SEM in embodiment 2 is intended to;
Fig. 3 is hemostatic material pictorial diagram in embodiment 2.
Specific embodiment
Below with reference to embodiment, the present invention will be described in further detail.It should be appreciated that specific reality described herein It applies example to be only used to explain the present invention, be not intended to limit the present invention.
Embodiment 1
(1) it weighs 25g pigskin gelatin to be added in 183g deionized water, is swollen 25min at normal temperature;
(2) gelatin solution of swelling is put into magnetic agitation 30min in 55 DEG C of water-bath, made it completely dissolved;
It (3) is 40-45 DEG C in spinning solution temperature, environment temperature is 30-35 DEG C, in the case that hot-air is annular cross air blasting Electrostatic spinning, lace curtaining revolving speed are 8r/min;
(4) spiral electrostatic spinning mode, voltage 60kv, electric current 0.12mA are used, spinning distance is 15cm;
(5) polarization method used is Filamentous corona polarizing, and voltage 60kv, electric current 3mA, polarization distance is 10cm;
(6) glutin nano fabric film is obtained after drying for 24 hours, to be sealed with sterilizing bag, epoxy second in 40 DEG C of vacuum ovens Alkane sterilizing is placed on 4 DEG C of preservations;
(7) detection spinning fibre diameter is in normal distribution, and main distribution is 320-1100nm;
(8) gelatine nano fiber hemostatic material 0.03g, existing market control sample 0.03g and blank sample are taken, according to 0.01g/ Pooled plasma 3.0mL is added in the ratio of mL, and 3 Duplicate Samples are arranged, is placed under (37 ± 1) DEG C biochemical cultivation case and incubates 1h, with solidifying Blood zymogen time assay kit and Standard for semi-Automated Blood Coagulation Analyzer measure its setting time.Measurement result are as follows: blank group 9.7 ± 0.1s, market samples control group are 20.2 ± 3.3s, and gelatine nano fiber hemostatic material is 8.4 ± 0.2s.Have between three aobvious Write difference.
Embodiment 2
Using device shown in FIG. 1.
(1) it weighs 18g ox bone gelatin to be added in 207g deionized water, is swollen 20min at normal temperature;
(2) gelatin solution of swelling is put into magnetic agitation 30min in 60 DEG C of water-bath, made it completely dissolved;
It (3) is 40-45 DEG C in spinning solution temperature, environment temperature is 30-35 DEG C, in the case that hot-air is annular cross air blasting Electrostatic spinning, lace curtaining revolving speed are 10r/min;
(4) spiral electrostatic spinning mode, voltage 60kv, electric current 0.12mA are used, spinning distance is 17cm;
(5) polarization method used is Filamentous corona polarizing, and voltage 60kv, electric current 3mA, polarization distance is 10cm;
(6) glutin nano fabric film is obtained after drying for 24 hours, to be sealed with sterilizing bag, epoxy second in 40 DEG C of vacuum ovens Alkane sterilizing is placed on 4 DEG C of preservations;
(7) detection spinning fibre diameter is in normal distribution, and main distribution is 260-1300nm;
The hemostatic material fibre structure SEM that embodiment 2 obtains is intended to as shown in Fig. 2, pictorial diagram is as shown in Figure 3.
(8) gelatine nano fiber hemostatic material 0.06g, existing market control sample 0.06g and blank sample are taken, according to 0.02g/ Pooled plasma 3.0mL is added in the ratio of mL, and 3 Duplicate Samples are arranged, is placed under (37 ± 1) DEG C biochemical cultivation case and incubates 1h, with solidifying Blood zymogen time assay kit and Standard for semi-Automated Blood Coagulation Analyzer measure its setting time.Measurement result are as follows: blank group 9.7 ± 0.1s, market samples control group are 28.3 ± 5.8s, and gelatine nano fiber hemostatic material is 8.1 ± 0.1s.Have between three aobvious Write difference.
Embodiment 3
(1) it weighs 18g collagen to be added in 282g hexafluoroisopropanol, magnetic agitation dissolves 60min at normal temperature;
(2) solution stand bubble removing 30min, clarify it completely;
It (3) is 20-25 DEG C in spinning solution temperature, environment temperature is 25-30 DEG C, in the case that hot-air is annular cross air blasting Electrostatic spinning, lace curtaining revolving speed are 10r/min;
(4) Multi needle electrostatic spinning mode, voltage 30kv, electric current 0.12mA are used, extrusion output is the hole 0.5ml/h/, Spinning distance is 15cm;
(5) polarization method used is needle-shaped corona polarizing, and voltage 60kv, electric current 3mA, polarization distance is 10cm;
(6) nano fibrous membrane is obtained after drying for 24 hours, to be sealed with sterilizing bag, ethylene oxide goes out in 40 DEG C of vacuum ovens Bacterium is placed on 4 DEG C of preservations;
(7) detection spinning fibre diameter is in normal distribution, and main distribution is 350-1200nm;
(8) nanofiber hemostatic material 0.06g, existing market control sample 0.06g and blank sample are taken, according to 0.02g/mL's Pooled plasma 3.0mL is added in ratio, and 3 Duplicate Samples are arranged, is placed under (37 ± 1) DEG C biochemical cultivation case and incubates 1h, use fibrin ferment Former time assay kit and Standard for semi-Automated Blood Coagulation Analyzer measure its setting time.Measurement result are as follows: 9.7 ± 0.1s of blank group, Market samples control group is 28.3 ± 5.8s, and gelatine nano fiber hemostatic material is 8.6 ± 0.2s.There is significance difference between three It is different.
Embodiment 4
(1) it weighs 18g collagen to be added in 282g hexafluoroisopropanol, magnetic agitation dissolves 60min at normal temperature;
(2) solution stand bubble removing 30min, clarify it completely;
It (3) is 20-25 DEG C in spinning solution temperature, environment temperature is 25-30 DEG C, in the case that hot-air is annular cross air blasting Electrostatic spinning, lace curtaining revolving speed are 8r/min;
(4) spiral electrostatic spinning mode, voltage 80kv, electric current 0.25mA are used, spinning distance is 20cm;
(5) polarization method used is Filamentous corona polarizing, and voltage 60kv, electric current 3mA, polarization distance is 10cm;
(6) glutin nano fabric film is obtained after drying for 24 hours, to be sealed with sterilizing bag, epoxy second in 40 DEG C of vacuum ovens Alkane sterilizing is placed on 4 DEG C of preservations;
(7) detection spinning fibre diameter is in normal distribution, and main distribution is 300-1100nm;
(8) gelatine nano fiber hemostatic material 0.03g, existing market control sample 0.03g and blank sample are taken, according to 0.01g/ Pooled plasma 3.0mL is added in the ratio of mL, and 3 Duplicate Samples are arranged, is placed under (37 ± 1) DEG C biochemical cultivation case and incubates 1h, with solidifying Blood zymogen time assay kit and Standard for semi-Automated Blood Coagulation Analyzer measure its setting time.Measurement result are as follows: blank group 9.7 ± 0.1s, market samples control group are 20.2 ± 3.3s, and gelatine nano fiber hemostatic material is 7.8 ± 0.1s.Have between three aobvious Write difference.
Embodiment 5
(1) it weighs the spongy fibroin fiber albumen of 90g to be added in 180g anhydrous formic acid, dissolves 180min at normal temperature;
(2) solution stand bubble removing 30min, clarify it completely;
It (3) is 20-25 DEG C in spinning solution temperature, environment temperature is 25-30 DEG C, in the case that hot-air is annular cross air blasting Electrostatic spinning, lace curtaining revolving speed are 12r/min;
(4) wire electrostatic spinning mode, voltage 45kv, electric current 0.10mA are used, spinning distance is 12cm;
(5) polarization method used is Filamentous corona polarizing, and voltage 60kv, electric current 3mA, polarization distance is 10cm;
(6) nano fibrous membrane is obtained after drying for 24 hours, to be sealed with sterilizing bag, ethylene oxide goes out in 40 DEG C of vacuum ovens Bacterium is placed on 4 DEG C of preservations;
(7) detection spinning fibre diameter is in normal distribution, and main distribution is 300-1100nm;
(8) nanofiber hemostatic material 0.03g, existing market control sample 0.03g and blank sample are taken, according to 0.01g/mL's Pooled plasma 3.0mL is added in ratio, and 3 Duplicate Samples are arranged, is placed under (37 ± 1) DEG C biochemical cultivation case and incubates 1h, use fibrin ferment Former time assay kit and Standard for semi-Automated Blood Coagulation Analyzer measure its setting time.Measurement result are as follows: 9.7 ± 0.1s of blank group, Market samples control group is 20.2 ± 3.3s, and gelatine nano fiber hemostatic material is 8.6 ± 0.4s.There is significance difference between three It is different.
Embodiment 6
(1) it weighs the spongy fibroin fiber albumen of 90g to be added in 180g anhydrous formic acid, dissolves 180min at normal temperature;
(2) solution stand bubble removing 30min, clarify it completely;
It (3) is 20-25 DEG C in spinning solution temperature, environment temperature is 25-30 DEG C, in the case that hot-air is annular cross air blasting Electrostatic spinning, lace curtaining revolving speed are 12r/min;
(4) sheet metal electrostatic spinning mode, voltage 60kv, electric current 0.12mA are used, spinning distance is 15cm;
(5) polarization method used is soft X-ray polarization, and voltage 40kv, electric current 6mA, polarization distance is 10cm, vertically Irradiation intensity 10keV;
(6) nano fibrous membrane is obtained after drying for 24 hours, to be sealed with sterilizing bag, ethylene oxide goes out in 40 DEG C of vacuum ovens Bacterium is placed on 4 DEG C of preservations;
(7) detection spinning fibre diameter is in normal distribution, and main distribution is 320-1100nm;
(8) nanofiber hemostatic material 0.03g, existing market control sample 0.03g and blank sample are taken, according to 0.01g/mL's Pooled plasma 3.0mL is added in ratio, and 3 Duplicate Samples are arranged, is placed under (37 ± 1) DEG C biochemical cultivation case and incubates 1h, use fibrin ferment Former time assay kit and Standard for semi-Automated Blood Coagulation Analyzer measure its setting time.Measurement result are as follows: 9.7 ± 0.1s of blank group, Market samples control group is 20.2 ± 3.3s, and gelatine nano fiber hemostatic material is 7.6 ± 0.1s.There is significance difference between three It is different.
Embodiment 7
(1) it weighs 25g pigskin gelatin to be added in 200g deionized water, is swollen 25min at normal temperature;
(2) gelatin solution of swelling is put into magnetic agitation 30min in 55 DEG C of water-bath, made it completely dissolved;
It (3) is 40-45 DEG C in spinning solution temperature, environment temperature is 30-35 DEG C, in the case that hot-air is annular cross air blasting Electrostatic spinning, lace curtaining revolving speed are 8r/min;
(4) spiral electrostatic spinning mode, voltage 60kv, electric current 0.12mA are used, spinning distance is 15cm;
(5) polarization method used is thermal poling, and voltage 40kv, electric current 2mA, polarization distance is 10cm, polarization temperature Degree is 70 DEG C;
(6) glutin nano fabric film is obtained after drying for 24 hours, to be sealed with sterilizing bag, epoxy second in 40 DEG C of vacuum ovens Alkane sterilizing is placed on 4 DEG C of preservations;
(7) detection spinning fibre diameter is in normal distribution, and main distribution is 320-1100nm;
(8) gelatine nano fiber hemostatic material 0.03g, existing market control sample 0.03g and blank sample are taken, according to 0.01g/ Pooled plasma 3.0mL is added in the ratio of mL, and 3 Duplicate Samples are arranged, is placed under (37 ± 1) DEG C biochemical cultivation case and incubates 1h, with solidifying Blood zymogen time assay kit and Standard for semi-Automated Blood Coagulation Analyzer measure its setting time.Measurement result are as follows: blank group 9.7 ± 0.1s, market samples control group are 20.2 ± 3.3s, and gelatine nano fiber hemostatic material is 8.3 ± 0.2s.Have between three aobvious Write difference.

Claims (9)

1. a kind of preparation method of protide high polymer nanometer fiber hemostatic material, which is characterized in that included following steps:
(1) protide macromolecule dissolution is configured to spinning solution;
(2) protide macromolecule is prepared by electrostatic spinning the nanofiber of tridimensional network;
(3) nanofiber of tridimensional network is polarised in polarized electric field;
(4) nanofiber of the tridimensional network after polarization process is dried and sterilizes, and obtains protide high molecular nanometer Fiber hemostatic material.
2. a kind of preparation method of protide high polymer nanometer fiber hemostatic material according to claim 1, which is characterized in that The method of the electrostatic spinning is, using single or mixed liquor as solvent, using protide macromolecule as solute, adjusts spinning ginseng Molecular chain orientation arrangement is prepared in number, fiber surface is distributed the Nanowires with three-dimensional net structure of a variety of hydrophilic radicals Tie up material.
3. a kind of preparation method of protide high polymer nanometer fiber hemostatic material according to claim 2, feature exist In the solvent is water, formic acid, acetic acid, propionic acid, trifluoroethanol, hexafluoroisopropanol, Hexafluoro acetone, dimethylformamide, two The mixing of one of methylacetamide, acetone, ketone, butanone, cyclohexanone, ethyl alcohol, methanol or more than one solvents composition Solvent;
The protide macromolecule be collagen, gelatin, fibroin albumen, spider silk fibroin, elastin laminin, zeins, One or more than one kinds of compositions in polypeptide;
The spinning parameter, including concentration of dope is between 2%~40%, spinning voltage between 5~90kV, spinning away from From between 5~30cm, spinning solution temperature is at 0~70 DEG C, 0~65 DEG C of environment temperature.
4. a kind of preparation method of protide high polymer nanometer fiber hemostatic material according to claim 1, which is characterized in that The polarization process, refers in polarized electric field, and electrospinning protide fibrous inside forms polarization charge or dipole, carboxyl and The orderly polarization offset of amino charged group, and the charge intensified in a large amount of electric fields is adsorbed, form intrastitial space bound charge.
5. a kind of preparation method of protide high polymer nanometer fiber hemostatic material according to claim 4, which is characterized in that The polarization mode includes corona polarizing, thermal poling, the polarization of soft X-ray, radiation-polarizing and magnetic polarization.
6. a kind of preparation method of protide high polymer nanometer fiber hemostatic material according to claim 1, which is characterized in that The drying, is dried in a vacuum drying oven, and for drying temperature at 35-80 DEG C, drying time is no more than 48h.
7. a kind of preparation method of protide high polymer nanometer fiber hemostatic material according to claim 1, which is characterized in that The sterilizing, including ethylene oxide sterilizing, ultraviolet sterilization or radiosterilization.
8. a kind of protide high polymer nanometer fiber hemostatic material, which is characterized in that by any method system of claims 1 to 7 Standby gained.
9. a kind of application of protide high polymer nanometer fiber hemostatic material according to claim 8, which is characterized in that make For hemostatic material.
CN201910680967.1A 2019-07-26 2019-07-26 A kind of protide high polymer nanometer fiber hemostatic material and its preparation method and application Pending CN110433325A (en)

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CN111569143A (en) * 2020-05-14 2020-08-25 山东省科学院生物研究所 Snake venom prothrombin activator and rapid hemostatic material based on same
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CN112795995A (en) * 2021-02-03 2021-05-14 常州市武进人民医院 Dry spinning method for medical hemostatic fiber and manufacturing method thereof

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