CN109172073A - A kind of the Electrospun nano-fibers film and oesophagus overlay film memory bracket of controlled release growth factor - Google Patents
A kind of the Electrospun nano-fibers film and oesophagus overlay film memory bracket of controlled release growth factor Download PDFInfo
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- CN109172073A CN109172073A CN201811019894.3A CN201811019894A CN109172073A CN 109172073 A CN109172073 A CN 109172073A CN 201811019894 A CN201811019894 A CN 201811019894A CN 109172073 A CN109172073 A CN 109172073A
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- solution
- sandwich layer
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- oesophagus
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Classifications
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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- A—HUMAN NECESSITIES
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
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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
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- A—HUMAN NECESSITIES
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
Abstract
The present invention relates to a kind of Electrospun nano-fibers film of controlled release growth factor and oesophagus overlay film memory brackets.The Electrospun nano-fibers film of the controlled release growth factor, shell solution are the polylactic acid caprolactone copolymer solution using hexafluoroisopropanol as solvent, and sandwich layer solution is the aqueous solution of EGF albumen, are prepared using the method for Dispersion relation.The oesophagus overlay film memory bracket include the first fixing end, the second fixing end, outer diameter 40-50mm rack body, the entire outer wall of second fixing end and rack body coats the Electrospun nano-fibers film of the controlled release growth factor, and the first fixing end is made of several diaphragms with tension.The present invention provides a kind of new method to treat without narrow or obstruction esophageal injury, the oesophagus overlay film memory bracket can be used for without narrow or obstruction esophageal injury and be not easy to dislocate, the Electrospun nano-fibers film slow release effect that it is loaded is excellent, protein active maintains, and can remarkably promote esophageal injury reparation.
Description
Technical field
The present invention relates to the field of medical instrument technology, specifically, the electrostatic spinning for being related to a kind of controlled release growth factor is received
Rice tunica fibrosa and oesophagus overlay film memory bracket.
Background technique
Esophageal Stent is most common tool in various good pernicious esophagel disease treatments, and effect includes inner support, can be had
Effect releases thoracic choke, prevents the generation of lemostenosis, is conducive to feed nutrition, helps physical strength functional rehabilitation.Esophageal Stent is conventional
Patient's body certain time need to be retained in.These Esophageal Stents put universal principle, after bracket is put, because itself remembers
Expansive force makes the bracket clamp after expansion in stenosis, not easily shifted position.
And some has no obvious stenosis or obstruction patient, their oesophagus other parts are normal, and oesophagus only occurs
Oesophagus breakage caused by mucous membrane interruption and interior arthroscopic diagnosis is not repaired, it is often necessary to which open chest surgery, clinic lack effective food
Pipe holder is to help mucous membrane of esophagus reparation.
Generally speaking, at present clinically used Esophageal Stent be mostly release lemostenosis, obstruction and design, be not particularly suited for
Above-mentioned oesophagus is without narrow or obstruction patient.For this some patients, due to the similar bracket that not can be placed under scope, usually only
Energy surgical operation or conservative therapy, and these are treated, and the disease therapeuticing effect and life matter of patient are largely influenced
Amount.
Patent document CN201879873U, day for announcing 2011.06.29, to overcome conventional Recyclable Anti-reflux Esophageal Stents
Radial support power is small, the defects of granulation hyperplasia easily occur in both ends, and it is recyclable to provide a kind of super mouth of full overlay film of Ultimum Ti
Esophageal Stent, rack body both ends bulge, rack body are cylindrical body, and 40~160mm of total stent length is nickel-titanium shape memory
The reticular structure that alloy is woven into, bracket are integrally coated silica gel thin film, and the diameter of section of the rack body is 10~26mm, institute
The silica gel thin film stated forms skirt border structure beyond 5~10mm of collar extension of rack body upper end bulge.The Esophageal Stent is less prone to
The problems such as stent migration falls off, restenosis, bracket are difficult to take out, easy bleeding.
Patent document CN101984940A, publication date 2011.03.16, for solve traditional Esophageal Stent do not have prevention and
The problem for the treatment of esophageal fistula, disclose it is a kind of can load drug cover capsule Esophageal Stent, which is by inner support
Pipe and anther sac two parts composition, the inner support tube be bellows, bellows both ends respectively extend one have determine compared with Large Diameter Pipeline
Position is managed, and the bellows between two positioning pipes is active component, and the length of active component is greater than the length of diseased region；The anther sac
Cavity made of the one layer of elastomer seal wrapped up for the active component of bellows and its outside, on bellows active component
The drug-feeding tube communicated with anther sac is fixed at end pipe wall.The invention advantage is: bracket has certain axial bending benefit
In the placement of bracket, while again there is good radial strength can keep good channel, the bracket has better after powder charge
Elasticity, flexibility and good adhesion, can reduce damage of the bracket to diseased region, and it can be prevented to be subjected to displacement；It should
Bracket can also achieve the purpose that prevent and treat esophageal fistula, to mitigate the pain of patient.When selecting the bracket, it should make to prop up
The upper and lower mouth of frame exceeds narrow section (or diseased region) 10~20mm.
It can be seen that both the above Esophageal Stent is still all only applicable to the case where there are lemostenosis or obstructions, therefore
Oesophagus can effectively be treated without narrow or obstruction by needing one kind at present, but be occurred caused by mucous membrane of esophagus interruption or interior arthroscopic diagnosis
Oesophagus breakage such as does not repair at the new method or device of situations.
In addition, above patent document CN101984940A's covers capsule Esophageal Stent and can load drug, drug is from capsule when use
Interior exudation is gradually released in human body, achievees the purpose that prevent and treat esophageal fistula.However, this kind of drug release mode is not
Controllably, prevention or therapeutic effect can not accurately be expected.
Electrostrictive polymer spinning superfine fiber medicine delivery systme is fine using macromolecule medicament-carried nano made from electrostatic spinning
The diameter of dimension, the nanofiber of electrostatic spinning preparation is small, and surface area is big, utilizes it as medicine carrying material, can make contained medicine
Object slowly decomposes release, plays better therapeutic effect.The document report of superfine fiber medicine delivery systme is prepared in Electrospun
In road, the drug used has the chemicals such as antibiotic, antitumor/anticancer class drug, bioactie agent, such as: capillate thiophene
Cefoxitin Sodium (Mefoxin), rifampin, Itraconazole (Itraconazole), triumphant ear slow (Ketanserin),
Tetracycline hydrochloride, cefazolin (Cefazolin), taxol, adriamycin, doxorubicin hydrochloride, heparin etc., there are also
The report of protide bio-pharmaceutical can be discharged.The pharmaceutical carrier used is mainly total with the block of PLA, PGA and its different proportion
Based on polymers PLGA.Coaxial electrostatic spinning is the new method to grow up on conventional electrostatic spining technology, and single step can the company of preparation
Continuous shell-and-core structure nanofiber or hollow nanofiber.During Dispersion relation, protein solution and polymer organic
Solution is divided in two containers spinning simultaneously, reduces the time that protein is contacted with organic solution, is conducive to improve albumen
The stability of matter.Pattern and drug release characteristics, the pharmaceutical activity of medicament-carrying nano-fiber are influenced by electrospinning parameters, this
Concentration, molecular weight, electric conductivity, flow velocity, the voltage etc. of a little parameter such as solution, but each parameter and medicament-carrying nano-fiber structure at present
It is not fully understood with the relationship of performance.
In the repair process of oesophagus breakage, as being repaired using the quickening of electrostrictive polymer spinning superfine fiber medicine delivery systme
Multiple process, will greatly benefit patient.
Patent document CN107224619A, publication date 2017.10.03 disclose one kind and pass through coaxial electrostatic spinning technology
The method for preparing ICA-SF/PLCL nano fibrous membrane is to be dissolved in the solution formed in hexafluoroisopropanol as shell using SF and PLCL
Spinning solution using coaxial electrostatic spinning equipment, and controls Static Spinning using the ICA solution of 10-5 μm of ol/L as sandwich layer spinning solution
The optimal processing parameter of silk: core, shell spinning solution fltting speed are respectively 0.1mL/h and 1.0mL/h, and 25 DEG C of room temperature, relatively
Humidity 50 ± 6% is lower to carry out electrospinning, and for the film tentatively obtained using glutaraldehyde as crosslinking agent 48h, vacuum drying obtains ICA-SF/
PLCL nano fibrous membrane.External Osteoinductive differentiation and vivo applications are tested in bone defect shows that the ICA-SF/PLCL of preparation receives
Rice tunica fibrosa is sustainable, effectively discharges ICA and significant promotion ostosis, and no cytotoxicity.
Patent document CN106730038A, publication date 2017.05.31 are disclosed a kind of for tracheae soft tissue repair
Tunica fibrosa and preparation method thereof, it is specific the preparation method comprises the following steps: prepared by (1) Shell Materials: in mass ratio by polycaprolactone and Type I collagen
4:1 is dissolved in hexafluoroisopropanol and stirs 12 hours, is configured to polycaprolactone/Type I collagen mixed solution that mass concentration is 12%,
Then the bubble generated when ultrasonic treatment 30min removal stirring, is made Shell Materials mixed solution.(2) prepared by core layer material:
S1: it recombinant conversion growth factor-beta 3 (rhTGF- β 3) is added to gentle agitation 1h in phosphate buffer is configured to concentration and be
3 solution of rhTGF- β of 40 μ g/mL；S2: bovine serum albumin (BSA) is added to gentle agitation 1h in phosphate buffer and is configured
The BSA solution for being 200 μ g/mL at concentration；S3: by concentration made from S1 be 40 μ g/mL 3 solution of rhTGF- β and S2 made from
Concentration is that the BSA solution of 200 μ g/mL mixes in equal volume, is configured to the mixed solution of rhTGF- β 3/BSA；S4: Type I collagen is molten
The Type I collagen solution that mass concentration is 20% is made into deionized water；S5: the I type glue for being 20% by mass concentration made from S4
The mixed solution of rhTGF- β 3/BSA obtained mixes in equal volume in original solution and S3, and core layer material mixed solution is made.(3) it spins
Silk: S1: the Shell Materials mixed solution and the core layer material mixed solution are added separately in coaxial electrostatic spinning equipment
Shell Materials syringe and core layer material syringe in, stand 30-60min to draining the Shell Materials syringe and stratum nucleare
The air of materials injectors；S2: distance between adjusting roller receiver and Coaxial nozzle is 15-20cm, adjust high voltage power supply to
15~20kV, the output speed for adjusting the micro-injection pump for being loaded with Shell Materials syringe are adjusted to 1mL/h, and adjusting is loaded with stratum nucleare
The output speed of the micro-injection pump of materials injectors to 0.2mL/h, the revolving speed of roller receiver is controlled in 200~350rpm；
S4: after core layer material exports completely, terminate spinning, removed from collection device spinning film to get.
But it yet there are no the report that the medicament-carrying nano-fiber membrane of electrostatic spinning technique preparation is successfully applied to esophageal renovation
Road.
Summary of the invention
The purpose of the present invention is treating not good enough problem without narrow or obstruction esophageal injury for oesophagus in the prior art,
Provide the Electrospun nano-fibers film and oesophagus overlay film of oesophagus overlay film memory bracket cure and a kind of controlled release growth factor
Memory bracket.
In a first aspect, the present invention provides a kind of Electrospun nano-fibers film of controlled release growth factor, the electrostatic
Spinning nano fibrous membrane is prepared in accordance with the following methods:
(a) prepare Electrospun solution: shell solution is molten using hexafluoroisopropanol as the polylactic acid caprolactone copolymer of solvent
Liquid, concentration 0.06-0.10g/mL；For sandwich layer solution using ultrapure water as solvent, solute is EGF albumen；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into two syringes of co-axial electrospinning device, spinning electricity
Pressure is 14-16kV, and spray head to receiving device distance is 14-16cm, controls shell and sandwich layer stablizes flow velocity 0.013-0.017mL/
H, i.e.,.
As a preference, for the sandwich layer solution using ultrapure water as solvent, solute is EGF albumen, protein concentration 15-
25ng/ml。
As a preference, the Electrospun nano-fibers film is prepared in accordance with the following methods:
(a) prepare Electrospun solution: shell solution is molten using hexafluoroisopropanol as the polylactic acid caprolactone copolymer of solvent
Liquid, concentration 0.08g/mL；For sandwich layer solution using ultrapure water as solvent, solute is EGF albumen；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into two syringes of co-axial electrospinning device, spinning electricity
Pressure is 15kV, and spray head to receiving device distance is 15cm, controls shell and sandwich layer stablizes flow velocity 0.015mL/h.
Second aspect, the present invention provides a kind of preparation method of the Electrospun nano-fibers film of controlled release growth factor,
The following steps are included:
(a) prepare Electrospun solution: shell solution is molten using hexafluoroisopropanol as the polylactic acid caprolactone copolymer of solvent
Liquid, concentration 0.06-0.10g/mL；For sandwich layer solution using ultrapure water as solvent, solute is EGF albumen；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into two syringes of co-axial electrospinning device, spinning electricity
Pressure is 14-16kV, and spray head to receiving device distance is 14-16cm, controls shell and sandwich layer stablizes flow velocity 0.013-0.017mL/
h。
As a preference, the preparation method the following steps are included:
(a) prepare Electrospun solution: shell solution is molten using hexafluoroisopropanol as the polylactic acid caprolactone copolymer of solvent
Liquid, concentration 0.08g/mL；For sandwich layer solution using ultrapure water as solvent, solute is EGF albumen；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into two syringes of co-axial electrospinning device, spinning electricity
Pressure is 15kV, and spray head to receiving device distance is 15cm, controls shell and sandwich layer stablizes flow velocity 0.015mL/h.
The third aspect, the present invention provides Electrospun nano-fibers films as described above to promote tissue repair in preparation
Application in medical instrument.
As a preference, the medical instrument is Esophageal Stent.
Fourth aspect, the present invention provides a kind of oesophagus overlay film notes suitable for treating without narrow or obstruction esophageal injury
Recall bracket, which is characterized in that the oesophagus overlay film memory bracket both ends are respectively the first fixing end and the second fixing end, described
The first fixing end and the second fixing end between be rack body；The rack body is woven by memory wire, is in
Cylindrical tube, outer diameter 40-50mm；Second fixing end is woven by memory wire, in horn-like；Described second
The entire outer wall of fixing end and rack body coats film containing growth factor, and the film containing growth factor is electrostatic as described above
Spinning nano fibrous membrane；First fixing end is made of several diaphragms with tension, and the lower edge of diaphragm is connected to bracket
The upper limb of main body, these diaphragms round along the upper limb of rack body, and the diaphragm is in tight shape under use state.
As a preference, the lower edge outer diameter of second fixing end is 52-56mm.
As another preference, the diaphragm is half elliptic, semicircle or trapezoidal.
As another preference, the rack body upper limb is waveform, several grooves is equipped with, under the diaphragm
Inserted type is corrected to be connected in groove.
The invention has the advantages that:
1, present inventor is based on clinical experience abundant, without narrow or obstruction but occurs in mucous membrane of esophagus for oesophagus
Oesophagus breakage caused by disconnected or interior arthroscopic diagnosis such as does not repair at the situations, proposes the new method of Esophageal Stent treatment, and be based on this
Oesophagus overlay film memory bracket of the invention is devised, the main part outer diameter of the oesophagus overlay film memory bracket is larger, makes oesophagus
The method for placing Esophageal Stent can also be used in no narrow or obstruction esophageal injury treatment, effectively overcomes and takes surgery hand at present
The drawbacks of art or conservative therapy.
2, oesophagus overlay film memory bracket outer wall of the invention is equipped with the Electrospun nano-fibers film of controlled release growth factor, will
Growth factor is loaded into inside film, can promote the reparation of mucous membrane, and can also be effectively isolated oesophagus and the external world with the sustained release growth factor
Oesophagus outside organize.
3, the upper end of oesophagus overlay film memory bracket of the invention is made of several diaphragms with tension, use state lower film
Piece is bonded in tight state and by expansion with mucous membrane of esophagus inner wall, is provided biggish frictional force, can be played fixed function, prevent
Stent migration falls off；The especially whole tension from the bottom to top of diaphragm gradually reduces, therefore to the mucous membrane of esophagus at this position
With gradually decreased expansionary force, good mucosa is played.
4, the lower end of oesophagus overlay film memory bracket of the invention is in horn-like, and diameter is greater than rack body, therefore can prop up
Oesophagus inner wall is propped up, Esophageal Stent is effectively prevent to shift.
5, the present invention is prepared for the Electrospun nano-fibers film of controlled release growth factor EGF a kind of, using polylactic acid in oneself
The hexafluoroisopropanol solution of ester copolymer is as shell, and EGF protein solution is as sandwich layer, strict control cospinning parameter, especially
It is flow velocity, the Electrospun nano-fibers film slow release effect of preparation is excellent, and EGF activity remains preferable.It is carried on food of the invention
In tube covering membrane memory bracket, the reparation of esophageal injury can be remarkably promoted.
Detailed description of the invention
Attached drawing 1 is the oesophagus overlay film memory bracket main view of embodiment 1 (under complete release conditions).
Attached drawing 2 is the oesophagus overlay film memory bracket main view of embodiment 1 (under limit state).
Attached drawing 3 is the oesophagus overlay film memory bracket main view of embodiment 2 (under complete release conditions).
Specific embodiment
It elaborates with reference to the accompanying drawing to specific embodiment provided by the invention.
Appended drawing reference involved in attached drawing and component part are as follows:
1. 2. second fixing end of the first fixing end
3. 4. film containing growth factor of rack body
5. 6. groove of diaphragm
The oesophagus overlay film memory bracket (one) of the invention of embodiment 1
Referring to Figure 1, Fig. 1 is the oesophagus overlay film memory bracket main view of embodiment 1 (under complete release conditions).Described
The both ends of oesophagus overlay film memory bracket are respectively the first fixing end 1 and the second fixing end 2, first fixing end 1 and second
It is rack body 3 between fixing end 2.The rack body 3 is woven by memory wire, is in cylindrical tube, outer diameter 40-
50mm.Second fixing end 2 is also to be woven by memory wire, and in horn-like, the outer diameter of lower edge is 52-56mm.
The memory wire of second fixing end 2 and rack body 3 is integrated.Second fixing end 2 and bracket
The entire outer wall of main body 3 coats film containing growth factor 4.First fixing end 1 is made of several diaphragms 5；The film
Piece 5 have tension, be half elliptic, the lower edge of diaphragm 5 be it is linear, be connected to the upper limb of rack body 3；These 5 edges of diaphragm
The upper limb of rack body 3 round.
Oesophagus overlay film memory bracket application method of the invention are as follows:
It is the oesophagus overlay film memory bracket main view of embodiment 1 referring first to Fig. 2, Fig. 2 (under limit state).It is being not used
Under state, the oesophagus overlay film memory bracket is defined in the catheter, the memory metal of the second fixing end 2 and rack body 3
Silk is elongated, and is radially become smaller, and the diaphragm 5 is gathered to center, and the film containing growth factor 4 is in buckle condition.
Again referring to Figure 1, without narrow or obstruction but occur caused by mucous membrane of esophagus interruption or interior arthroscopic diagnosis for oesophagus
Oesophagus breakage such as does not repair at the situations, and under scope, patient will be equipped with conduit merging patient's food of the oesophagus overlay film memory bracket
In pipe, when the mucous membrane of esophagus position that need to be repaired is placed exactly in the section of rack body 3, the oesophagus overlay film memory branch is discharged
Frame, the outer wall of film containing growth factor 4 fits in mucous membrane of esophagus inner wall at this time, the mucous membrane of esophagus that need to be repaired and film containing growth factor 4
Contact, second fixing end 2 strut oesophagus, and the diaphragm 5 is also flared because of the expansion of memory wire radial direction in tight
Taut shape.Then these diaphragms 5 are separately fixed on mucous membrane of esophagus under scope with clip by patient, make the outer wall and food of diaphragm 5
The inner wall of pipe mucous membrane is bonded.
It should be noted that oesophagus overlay film memory bracket of the invention is suitable for oesophagus without narrow or obstruction but oesophagus occurs
The situation that oesophagus breakage caused by mucous membrane interruption or interior arthroscopic diagnosis is not repaired, therefore the outer diameter of rack body 3 is 40-50mm,
It can guarantee that film containing growth factor 4 fits in mucous membrane of esophagus inner wall substantially, this is designed as oesophagus without narrow or obstruction patient food
Pipe cell migration provides a kind of practicable new method.The film containing growth factor 4 is according to this specification embodiment
The Electrospun nano-fibers film of any method preparation of 3-7.Growth factor is loaded into inside film by film containing growth factor 4,
It can promote the reparation of mucous membrane with the sustained release growth factor, and can also be effectively isolated outside oesophagus and extraneous oesophagus and organize.Containing growth
Factor film 4 can be placed directly against the outer wall of the second fixing end 2 and rack body 3.First fixing end 1 has tension by several
Diaphragm 5 form, diaphragm 5 is bonded in tight state and by expansion with mucous membrane of esophagus inner wall under use state, provides biggish rub
Power is wiped, fixed function can be played, prevents oesophagus overlay film memory bracket of the invention from shifting and falls off.Especially diaphragm 5 it is whole by
Under supreme tension gradually reduce, therefore there is gradually decreased expansionary force to the mucous membrane of esophagus at the position, play very well
Mucosa.The preferred 50-200nm of 5 thickness of diaphragm, quantity can be 4-10 piece, and shape can also be semicircle, ladder
Shape or lower edge are the shape that straight line upper limb is any curve.For second fixing end 2 in horn-like, diameter is greater than bracket
Main body 3, therefore oesophagus inner wall can be supported, it effectively prevent Esophageal Stent to shift.
The oesophagus overlay film memory bracket (two) of the invention of embodiment 2
Referring to figure 3., Fig. 3 is the oesophagus overlay film memory bracket main view of embodiment 2 (under complete release conditions).Described
The both ends of oesophagus overlay film memory bracket are respectively the first fixing end 1 and the second fixing end 2, first fixing end 1 and second
It is rack body 3 between fixing end 2.The rack body 3 is woven by memory wire, is in cylindrical tube, outer diameter 40-
50mm, the upper limb of rack body 3 are waveform, are equipped with several grooves 6.Second fixing end 2 is also by memory wire
It weaves, in horn-like, the outer diameter of lower edge is 52-56mm.The memory metal of second fixing end 2 and rack body 3
Silk is integrated.The entire outer wall of second fixing end 2 and rack body 3 coats film containing growth factor 4.Described
First fixing end 1 is made of several diaphragms 5；The diaphragm 5 has tension, and for ellipse, the lower end of diaphragm 5 is placed exactly in
In groove 6, the upper end of diaphragm 5 exceeds the upper limb certain altitude of rack body 3.These diaphragms 5 along rack body 3 upper limb ring
Around one week.
The diaphragm 5 of the embodiment is just connect with groove 6 in inserted type, in a state of use, corrected under diaphragm 5 by
The stronger stretching expansion of the upper limb of rack body 3, stronger with oesophagus inner wall frictional force, fixed effect is stronger.The diaphragm 5
It can also be round, trapezoidal or other shapes.
The Electrospun nano-fibers film (one) of the invention of embodiment 3
(a) prepare Electrospun solution: shell solution is with polylactic acid that hexafluoroisopropanol (being purchased from Merck) is solvent in oneself
Ester copolymer (75:25) solution, concentration 0.08g/mL, for sandwich layer solution using ultrapure water as solvent, solute is recombined human EGF albumen
(being purchased from Gibco, article No. PHG0315), protein concentration 20ng/ml；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into coaxial electrostatic spinning equipment, and (SS-2535, Beijing Yongkang are worked in peace and contentment science and technology
Development Co., Ltd) two syringes in, spinning voltage 15kV, spray head to receiving device distance be 15cm, control shell
Stablize flow velocity 0.015mL/h with sandwich layer, when voltage is more than critical value, sandwich layer and shell solution are sprayed onto from inside and outside on the top of spray head
End, forms that superfine solution fluid flies to receiver and to be cured as diameter rapidly below ultra-fine in micron under the action of electric field
Fiber receives to form drug containing nano fibrous membrane at receiving device.
The Electrospun nano-fibers film (two) of the invention of embodiment 4
(a) prepare Electrospun solution: shell solution is with polylactic acid that hexafluoroisopropanol (being purchased from Merck) is solvent in oneself
Ester copolymer (75:25) solution, concentration 0.10g/mL, for sandwich layer solution using ultrapure water as solvent, solute is recombined human EGF albumen
(being purchased from Gibco, article No. PHG0315), protein concentration 15ng/ml；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into coaxial electrostatic spinning equipment, and (SS-2535, Beijing Yongkang are worked in peace and contentment science and technology
Development Co., Ltd) two syringes in, spinning voltage 14kV, spray head to receiving device distance be 14cm, control shell
Stablize flow velocity 0.017mL/h with sandwich layer, when voltage is more than critical value, sandwich layer and shell solution are sprayed onto from inside and outside on the top of spray head
End, forms that superfine solution fluid flies to receiver and to be cured as diameter rapidly below ultra-fine in micron under the action of electric field
Fiber receives to form drug containing nano fibrous membrane at receiving device.
The Electrospun nano-fibers film (three) of the invention of embodiment 5
(a) prepare Electrospun solution: shell solution is with polylactic acid that hexafluoroisopropanol (being purchased from Merck) is solvent in oneself
Ester copolymer (75:25) solution, concentration 0.06g/mL, for sandwich layer solution using ultrapure water as solvent, solute is recombined human EGF albumen
(being purchased from Gibco, article No. PHG0315), protein concentration 15ng/ml；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into coaxial electrostatic spinning equipment, and (SS-2535, Beijing Yongkang are worked in peace and contentment science and technology
Development Co., Ltd) two syringes in, spinning voltage 16kV, spray head to receiving device distance be 14cm, control shell
Stablize flow velocity 0.015mL/h with sandwich layer, when voltage is more than critical value, sandwich layer and shell solution are sprayed onto from inside and outside on the top of spray head
End, forms that superfine solution fluid flies to receiver and to be cured as diameter rapidly below ultra-fine in micron under the action of electric field
Fiber receives to form drug containing nano fibrous membrane at receiving device.
The Electrospun nano-fibers film (four) of the invention of embodiment 6
(a) prepare Electrospun solution: shell solution is with polylactic acid that hexafluoroisopropanol (being purchased from Merck) is solvent in oneself
Ester copolymer (75:25) solution, concentration 0.10g/mL, for sandwich layer solution using ultrapure water as solvent, solute is recombined human EGF albumen
(being purchased from Gibco, article No. PHG0315), protein concentration 25ng/ml；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into coaxial electrostatic spinning equipment, and (SS-2535, Beijing Yongkang are worked in peace and contentment science and technology
Development Co., Ltd) two syringes in, spinning voltage 16kV, spray head to receiving device distance be 16cm, control shell
Stablize flow velocity 0.013mL/h with sandwich layer, when voltage is more than critical value, sandwich layer and shell solution are sprayed onto from inside and outside on the top of spray head
End, forms that superfine solution fluid flies to receiver and to be cured as diameter rapidly below ultra-fine in micron under the action of electric field
Fiber receives to form drug containing nano fibrous membrane at receiving device.
The Electrospun nano-fibers film (five) of the invention of embodiment 7
(a) prepare Electrospun solution: shell solution is with polylactic acid that hexafluoroisopropanol (being purchased from Merck) is solvent in oneself
Ester copolymer (75:25) solution, concentration 0.08g/mL, for sandwich layer solution using ultrapure water as solvent, solute is recombined human EGF albumen
(being purchased from Gibco, article No. PHG0315), protein concentration 20ng/ml；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into coaxial electrostatic spinning equipment, and (SS-2535, Beijing Yongkang are worked in peace and contentment science and technology
Development Co., Ltd) two syringes in, spinning voltage 15kV, spray head to receiving device distance be 15cm, control shell
Stablize flow velocity 0.017mL/h with sandwich layer, when voltage is more than critical value, sandwich layer and shell solution are sprayed onto from inside and outside on the top of spray head
End, forms that superfine solution fluid flies to receiver and to be cured as diameter rapidly below ultra-fine in micron under the action of electric field
Fiber receives to form drug containing nano fibrous membrane at receiving device.
Comparative example 1
(a) prepare Electrospun solution: shell solution is the polylactic acid caprolactone with trifluoroethanol (being purchased from Merck) for solvent
Copolymer (75:25) solution, concentration 0.08g/mL, for sandwich layer solution using ultrapure water as solvent, solute is recombined human EGF albumen
(being purchased from Gibco, article No. PHG0315), protein concentration 20ng/ml；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into coaxial electrostatic spinning equipment, and (SS-2535, Beijing Yongkang are worked in peace and contentment science and technology
Development Co., Ltd) two syringes in, spinning voltage 15kV, spray head to receiving device distance be 15cm, control shell
Stablize flow velocity 0.015mL/h with sandwich layer, when voltage is more than critical value, sandwich layer and shell solution are sprayed onto from inside and outside on the top of spray head
End, forms that superfine solution fluid flies to receiver and to be cured as diameter rapidly below ultra-fine in micron under the action of electric field
Fiber receives to form drug containing nano fibrous membrane at receiving device.
Comparative example 2
(a) prepare Electrospun solution: shell solution is with polylactic acid that hexafluoroisopropanol (being purchased from Merck) is solvent in oneself
Ester copolymer (75:25) solution, concentration 0.10g/mL, for sandwich layer solution using ultrapure water as solvent, solute is recombined human EGF albumen
(being purchased from Gibco, article No. PHG0315), protein concentration 15ng/ml；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into coaxial electrostatic spinning equipment, and (SS-2535, Beijing Yongkang are worked in peace and contentment science and technology
Development Co., Ltd) two syringes in, spinning voltage 14kV, spray head to receiving device distance be 14cm, control shell
Stablize flow velocity 0.02mL/h with sandwich layer, when voltage is more than critical value, sandwich layer and shell solution are sprayed onto from inside and outside on the top of spray head
End, forms that superfine solution fluid flies to receiver and to be cured as diameter rapidly below ultra-fine in micron under the action of electric field
Fiber receives to form drug containing nano fibrous membrane at receiving device.
Comparative example 3
(a) prepare Electrospun solution: shell solution is with polylactic acid that hexafluoroisopropanol (being purchased from Merck) is solvent in oneself
Ester copolymer (75:25) solution, concentration 0.10g/mL, for sandwich layer solution using ultrapure water as solvent, solute is recombined human EGF albumen
(being purchased from Gibco, article No. PHG0315), protein concentration 25ng/ml；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved
After uniformly, shell solution and sandwich layer solution are injected separately into coaxial electrostatic spinning equipment, and (SS-2535, Beijing Yongkang are worked in peace and contentment science and technology
Development Co., Ltd) two syringes in, spinning voltage 16kV, spray head to receiving device distance be 16cm, control shell
Stablize flow velocity 0.01mL/h with sandwich layer, when voltage is more than critical value, sandwich layer and shell solution are sprayed onto from inside and outside on the top of spray head
End, forms that superfine solution fluid flies to receiver and to be cured as diameter rapidly below ultra-fine in micron under the action of electric field
Fiber receives to form drug containing nano fibrous membrane at receiving device.
8 extracorporeal releasing experiment of embodiment
Electrospun nano-fibers film and 5mL phosphate buffer prepared by 20mg embodiment 3-7 and comparative example 1-3
(pH 7.4) be added centrifuge tube in, be placed in 37 DEG C of constant temperature oscillation (100r/min) incubators, upon discharge 1,2,3,4,5,
7,9 days same time took supernatant 1 time, then sampled 1 time within every 7 days, until 30 days, every 100 μ L of sub-sampling, every sub-sampling is backward
The phosphate buffer that the Fresh of same volume is added in centrifuge tube is illustrated to operate by ELISA kit, with microplate reader in
Each hole OD value is measured at 450nm wavelength, calculates EGF concentration indirectly.3 parallel samples are taken, are calculated preparation (Q), are investigated
Slow release effect.It the results are shown in Table 1, it can be seen that the Electrospun nano-fibers film of embodiment 3-7 is being in slow release, and is sustained
Time maintains length, and the Electrospun nano-fibers film of comparative example 1-3 shows to be released in early period, and the release of later period EGF weakens.
1 Electrospun nano-fibers film EGF preparation (Q, %) of table
Proliferation experiment of the embodiment 9 to people's gastric mucosal cell
Electrospun nano-fibers film and 5mL phosphate buffer prepared by 100mg embodiment 3-7 and comparative example 1-3
(pH 7.4) is added in centrifuge tube, is placed in 37 DEG C of constant temperature oscillation (100r/min) incubators, the 30th day upon discharge takes
Clear liquid.110 μ L of CES-1 people's gastric mucosal cell (being purchased from ATCC) suspension is inoculated in 96 orifice plates, number of cells is that every 1ml contains 2
It 000, sets in 37 DEG C of cell incubators and cultivates 4h.It is taken out after 4h, by above-mentioned Electrospun nano-fibers film release in vitro supernatant
Liquid and negative control solution (pH7.4PBS) add in 96 orifice plates, and each dilution holes do 3 multiple holes.96 orifice plates are put into 37 DEG C thin
18h is cultivated in born of the same parents' incubator, culture medium is sucked out, and culture medium 100 μ L and CCK-8 examination is added in every hole after washing 1 time with pH 7.4PBS
10 μ L of agent, then set and stand 4h in incubator, it sets and measures each hole absorbance in microplate reader at 450nm.It the results are shown in Table 2, can see
Out, the EGF of the Electrospun nano-fibers film release of embodiment 3-7 keeps higher bioactivity, compared to comparative example 1-3's
The EGF bioactivity of Electrospun nano-fibers film release has significant difference.
2 cell proliferative conditions of table
Note: compared with comparative example 1, P < 0.05；#, compared with comparative example 2, P < 0.05；△, compared with comparative example 3, P <
0.05。
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
Member, under the premise of not departing from the method for the present invention, can also make several improvement and supplement, these are improved and supplement also should be regarded as
Protection scope of the present invention.
Claims (10)
1. a kind of Electrospun nano-fibers film of controlled release growth factor, which is characterized in that the Electrospun nano-fibers
Film is prepared in accordance with the following methods:
(a) prepare Electrospun solution: shell solution is the polylactic acid caprolactone copolymer solution using hexafluoroisopropanol as solvent, dense
Degree is 0.06-0.10g/mL；For sandwich layer solution using ultrapure water as solvent, solute is EGF albumen；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved uniformly
Afterwards, shell solution and sandwich layer solution are injected separately into two syringes of co-axial electrospinning device, spinning voltage is
14-16kV, spray head to receiving device distance is 14-16cm, controls shell and sandwich layer stablizes flow velocity 0.013-0.017mL/h, i.e.,
's.
2. Electrospun nano-fibers film according to claim 1, which is characterized in that the Electrospun nano-fibers
Film is prepared in accordance with the following methods:
(a) prepare Electrospun solution: shell solution is the polylactic acid caprolactone copolymer solution using hexafluoroisopropanol as solvent, dense
Degree is 0.08g/mL；For sandwich layer solution using ultrapure water as solvent, solute is EGF albumen；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved uniformly
Afterwards, shell solution and sandwich layer solution are injected separately into two syringes of co-axial electrospinning device, spinning voltage is
15kV, spray head to receiving device distance is 15cm, controls shell and sandwich layer stablizes flow velocity 0.015mL/h.
3. a kind of preparation method of the Electrospun nano-fibers film of controlled release growth factor, which comprises the following steps:
(a) prepare Electrospun solution: shell solution is the polylactic acid caprolactone copolymer solution using hexafluoroisopropanol as solvent, dense
Degree is 0.06-0.10g/mL；For sandwich layer solution using ultrapure water as solvent, solute is EGF albumen；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved uniformly
Afterwards, shell solution and sandwich layer solution are injected separately into two syringes of co-axial electrospinning device, spinning voltage is
14-16kV, spray head to receiving device distance is 14-16cm, controls shell and sandwich layer stablizes flow velocity 0.013-0.017mL/h.
4. preparation method according to claim 3, which comprises the following steps:
(a) prepare Electrospun solution: shell solution is the polylactic acid caprolactone copolymer solution using hexafluoroisopropanol as solvent, dense
Degree is 0.08g/mL；For sandwich layer solution using ultrapure water as solvent, solute is EGF albumen；
(b) Dispersion relation: being 18-20 DEG C, humidity 45-50% in environment temperature, shell and sandwich layer solution are completely dissolved uniformly
Afterwards, shell solution and sandwich layer solution are injected separately into two syringes of co-axial electrospinning device, spinning voltage is
15kV, spray head to receiving device distance is 15cm, controls shell and sandwich layer stablizes flow velocity 0.015mL/h.
5. Electrospun nano-fibers film of any of claims 1 or 2 answering in the medical instrument that preparation promotes tissue repair
With.
6. application according to claim 5, which is characterized in that the medical instrument is Esophageal Stent.
7. a kind of oesophagus overlay film memory bracket suitable for treating without narrow or obstruction esophageal injury, which is characterized in that described
Oesophagus overlay film memory bracket both ends be respectively the first fixing end and the second fixing end, first fixing end and second fixed
It is rack body between end；The rack body is woven by memory wire, is in cylindrical tube, outer diameter 40-50mm；Institute
The second fixing end stated is woven by memory wire, in horn-like；Second fixing end and rack body it is entire
Outer wall coats film containing growth factor, and the film containing growth factor is Electrospun nano-fibers of any of claims 1 or 2
Film；First fixing end is made of several diaphragms with tension, and the lower edge of diaphragm is connected to the upper limb of rack body, this
A little diaphragms round along the upper limb of rack body, and the diaphragm is in tight shape under use state.
8. oesophagus overlay film memory bracket according to claim 7, which is characterized in that outside the lower edge of second fixing end
Diameter is 52-56mm.
9. oesophagus overlay film memory bracket according to claim 7, which is characterized in that the diaphragm is half elliptic, partly
It is round or trapezoidal.
10. oesophagus overlay film memory bracket according to claim 7, which is characterized in that the rack body upper limb is wave
Shape wave is equipped with several grooves, corrects inserted type under the diaphragm and be connected in groove.
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| CN113183594A (en) * | 2021-04-07 | 2021-07-30 | 广东工业大学 | Preparation method of electrostatic spinning functional nanofiber film for epidermis repair |
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| JP5010854B2 (en) * | 2006-05-18 | 2012-08-29 | 帝人株式会社 | Revascularization material |
| CN101509153A (en) * | 2009-03-23 | 2009-08-19 | 东华大学 | Method for producing shell-core structure medicament nano-fibre with coaxial electrostatic spinning technology |
| CN101984940A (en) * | 2010-11-03 | 2011-03-16 | 华南理工大学 | Sac-covered esophagus scaffold capable of loading medicaments and preparation method thereof |
| CN201879873U (en) * | 2010-11-26 | 2011-06-29 | 江苏省人民医院 | Recyclable esophageal stent of nickel titanium memory alloy full-membrane exceeding opening |
| CN103893819B (en) * | 2014-03-20 | 2015-07-15 | 北京大学第三医院 | Coaxial electrostatic spinning fibrous scaffold and preparation method thereof |
| KR20170070008A (en) * | 2014-08-15 | 2017-06-21 | 더 존스 홉킨스 유니버시티 | Composite material for tissue restoration |
| CN106823011A (en) * | 2017-01-23 | 2017-06-13 | 重庆三峡医药高等专科学校 | The method and product for promoting EGF continuation release nanofiber are prepared using electrostatic spinning technique |
| CN107881650A (en) * | 2017-05-10 | 2018-04-06 | 佛山今兰生物科技有限公司 | A kind of coaxial double-layer electrostatic spinning prepares the method and its application of the nano fibrous membrane with core/shell embedding structure |
| CN108324986B (en) * | 2018-05-03 | 2021-09-07 | 东华大学 | Multifunctional ordered-release medical dressing film for acute wounds and preparation method thereof |
| CN209474880U (en) * | 2018-09-03 | 2019-10-11 | 上海市第一人民医院 | A kind of oesophagus overlay film memory bracket suitable for treating without narrow or obstruction esophageal injury |
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