CN106693059A - Composite tissue repair patch and preparation method and application thereof - Google Patents
Composite tissue repair patch and preparation method and application thereof Download PDFInfo
- Publication number
- CN106693059A CN106693059A CN201611238612.XA CN201611238612A CN106693059A CN 106693059 A CN106693059 A CN 106693059A CN 201611238612 A CN201611238612 A CN 201611238612A CN 106693059 A CN106693059 A CN 106693059A
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- Prior art keywords
- sticking patch
- pasting material
- fibrous membrane
- material solution
- mesh sheet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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Abstract
The invention relates to a composite tissue repair patch and a preparation method and application thereof. The composite tissue repair patch comprises a nanofiber membrane, a woven mesh and an adhesive material, wherein the adhesive material is located between the nanofiber membrane and the woven mesh; the adhesive material contains hydrophilic substances, the nanofiber membrane and the woven mesh are bonded through the adhesive material, and the adhesive material is embedded into pores of the nanofiber membrane and the woven mesh; the peel strength between the nanofiber membrane and the woven mesh is 20-75 cN/mm; the breaking strength of the composite tissue repair patch is 8-12.5 Mpa; preferably, the breaking elongation of the composite tissue repair patch is 20%-250%; more preferably, the porosity of the composite tissue repair patch is 50%-90%. The composite tissue repair patch is not likely to be layered and has the good mechanical property and soft characteristic.
Description
Technical field
Sticking patch and its preparation method and application is repaired the present invention relates to a kind of complex tissue, belongs to implantable medical material neck
Domain.
Background technology
At present, conventional tissue repairing patch includes braiding mesh sheet and Electrospun nano-fibers film.Braiding mesh sheet tool
There is good mechanical property, enough mechanical supports can be provided.But, due to braiding mesh sheet exist hardness big, rough surface,
Easily and the problems such as tissue adhesion, accordingly, it is difficult to obtain preferable repairing effect.
The features such as Electrospun nano-fibers film has great specific surface area, high porosity and high surface energy, Neng Gouzuo
It is the porous support of cell growth, promotes the migration of cell；Also there is three-dimensional porous structure, it is easy to convey nutrition and oxygen with profit
Propagation and differentiation in cell.Therefore, Electrospun nano-fibers film has good tissue repair performance.But electrostatic spinning
The mechanical strength of nano fibrous membrane is weaker, it is impossible to directly apply to tissue repair (such as hernia of mechanical strength requirement higher part position
Gas is repaired).
In the prior art, the combination of braiding mesh sheet and Electrospun nano-fibers film mainly has hot pressing, welding, bonding
Or nanofibers are received first-class in braiding mesh sheet.Wherein, hot pressing and welding is required to temperature higher, processing technology
It is difficult to control to, is easily destroyed the structure of braiding mesh sheet or Electrospun nano-fibers film.Bond the material of the adhesive to being used
Material is poor with the compatibility of tissue, and easily and tissue adhesion, and the intensity of bonding is relatively low.And directly receive nanofibers
Processing mode and insecure (preparation of Chen Yanchun etc., PP/PLA basin bottom composite patch and performance [J], east in braiding mesh sheet
Magnificent college journal (natural science edition), 2014,40 (6):687-691), easily it is layered in Clinical practice, it is impossible to realize repairing
Effect.
Patent application document CN105435309A discloses the composite patch of a kind of static spinning membrane and braiding mesh sheet, described
Composite patch is combined by way of hot pressing and is obtained using the relatively low adhesive layer of fusing point.But its adhesion-layer materials for using
Fusing point must be far below the fusing point of electrostatic spinning film material, to prevent from destroying during subsequent thermal pressure the knot of electrostatic spinning film layer
Structure, compound technique is more complicated, and composite patch porosity.
The content of the invention
Problems to be solved by the invention
The present invention provides a kind of complex tissue and repairs sticking patch and its preparation method and application.Complex tissue reparation of the invention
Effectively be combined for nano fibrous membrane and braiding mesh sheet so that the complex group by sticking patch by using suitable pasting material
Knitting reparation sticking patch not only has good mechanical property, enough mechanical supports can be provided, also with good bio-compatible
Property.
Further, the present invention also provides a kind of method for preparing complex tissue reparation sticking patch, not only remains Nanowire
Tie up the characteristic of film original structure, additionally it is possible to improve the biocompatibility of braiding mesh sheet.
The scheme for solving problem
The present invention provides a kind of complex tissue and repairs sticking patch, and the complex tissue repairs sticking patch to be included：
Nano fibrous membrane, braiding mesh sheet and pasting material, wherein, the pasting material is located at the nano fibrous membrane and institute
State braiding mesh sheet between；
The pasting material includes hydroaropic substance, and the nano fibrous membrane and the braiding mesh sheet stick material by described
Material is combined, and the pasting material is embedded into the hole of the nano fibrous membrane and the braiding mesh sheet；
Peel strength between the nano fibrous membrane and the braiding mesh sheet is 20~75cN/mm；The complex tissue
The fracture strength for repairing sticking patch is 8~12.5Mpa；Preferably, the complex tissue repair the extension at break amount of sticking patch for 20~
250%；It is highly preferred that the porosity that the complex tissue repairs sticking patch is 50~90%.
Complex tissue of the invention repairs sticking patch, wherein, the complex tissue repairs sticking patch also includes antiblocking layers,
The antiblocking layers are attached on the face opposite with side where nano fibrous membrane of the braiding mesh sheet.
Complex tissue of the invention repairs sticking patch, the weight average molecular weight of the hydroaropic substance for 50000~
2000000Da。
Complex tissue of the invention repairs sticking patch, and the hydroaropic substance includes：Containing nitrogen compound and its derivative
Thing, cellulose compound and its derivative, alcohol compound and its derivative, shitosan class compound and its derivative, sugar
One or more in class compound and its derivative.
Complex tissue of the invention repairs sticking patch, described to include protein-based compound containing nitrogen compound, preferably
One or two in including collagen, gelatin；The shitosan class compound includes：Carboxymethyl chitosan, hydroxypropyl base enclosure
One or two in glycan；The cellulose compound includes：One kind in carboxymethylcellulose calcium, sodium carboxymethylcellulose
Or two kinds.
Complex tissue of the invention repairs sticking patch, and the hydroaropic substance includes modified hydroaropic substance, preferably
The hydroaropic substance obtained including being modified by crosslinking agent.
Complex tissue of the invention repairs sticking patch, and the nano fibrous membrane is 0.1 with the distance between mesh sheet is woven
~3mm；Preferably 0.2~2mm.
Complex tissue of the invention repairs sticking patch, and the nano fibrous membrane uses the method for including electrostatic spinning step
It is obtained.
Complex tissue of the invention repairs sticking patch, the nano fibrous membrane by a diameter of 10nm~100 μm fiber
Silk is interwoven, it is preferable that the filament is made up of degradation material, it is highly preferred that the degradation material includes poly- breast
Acid, PDLLA, polycaprolactone, polyhydroxyalkanoate, PGA, poly--lactide is handed over；Collagen, gelatin, shell
One or more in glycan, hyaluronic acid, cellulose.
Complex tissue of the invention repairs sticking patch, and medicine is loaded with the nano fibrous membrane, and the medicine is preferred
Including growth factor；More preferably include EGF, fibroblast growth factor in one or two.
Complex tissue of the invention repairs sticking patch, and the braiding mesh sheet is made up of non-degradable material, it is preferable that institute
Stating non-degradable material includes polypropylene, polyvinylidene fluoride, gathers in the tetracid glycol ester of benzene two, expanded polytetrafluoroethylsealing
One or more.
The present invention also provides the preparation method that a kind of complex tissue of the invention repairs sticking patch, including：
Composite steps：Pasting material solution is prepared, the nano fibrous membrane and the braiding mesh sheet are sticked into material described in
Material is solution combined to obtain the complex tissue reparation sticking patch；
Preferably, using the pasting material solution, will be described by freeze drying process, coating processes or casting technique
Nano fibrous membrane is combined with the braiding mesh sheet.
The method according to the invention, adjusts the molecular weight of the pasting material and/or the concentration of the pasting material solution,
So that the pasting material solution from it is described braiding mesh sheet hole in overflow and it is described braiding mesh sheet and nano fibrous membrane
The solution layer that prevents adhesion is formed on the opposite face in place side.
The method according to the invention, the freeze drying process is comprised the following steps：
By hydroaropic substance dissolving, pasting material solution is obtained；
The pasting material solution is laid on the nano fibrous membrane, and is stood；
The braiding mesh sheet is laid on the pasting material solution, obtaining the complex tissue by freeze-drying repaiies
Multiple sticking patch.
The method according to the invention, in the freeze drying process, the thickness of the pasting material solution is 0.1~3mm,
It is preferred that 0.2~2mm；The time of the standing is 1~24h, preferably 3~6h；In the pasting material solution, the matter of pasting material
Amount concentration is 0.1~20%, preferably 5~15%；Preferably, the pre-freezing temperature of the freeze drying process is -80~-10
DEG C, preferably -80~-50 DEG C；Drying temperature is -20~30 DEG C, preferably -10~25 DEG C.
The method according to the invention, in the freeze drying process, the hydroaropic substance includes cellulose compound
And/or its derivative, preferably include one or more of hydroxyethyl cellulose, carboxymethylcellulose calcium, hydroxypropyl methyl cellulose；
Preferably, the hydroaropic substance includes the cellulose compound and/or its derivative of modified treatment, preferably includes through changing
Property treatment hydroxyethyl cellulose, carboxymethylcellulose calcium, hydroxypropyl methyl cellulose one or more.
The method according to the invention, in the freeze drying process, the modification includes：Handed over using crosslinking agent
The step of connection reaction；Preferably, the crosslinking agent includes aldehyde compound, preferably includes the one kind in formaldehyde, acetaldehyde, glutaraldehyde
Or it is various, more preferably including glutaraldehyde.
The method according to the invention, in the freeze drying process, the modification also includes：Carried out in salting liquid
Cross-linking reaction；Preferably, the salt include neutral salt, it is highly preferred that the neutral salt be water-soluble aluminum salt, sodium salt, calcium salt and
One or more in molysite.
The method according to the invention, in the freeze drying process, the modification is carried out in the solution, preferably
Ground, the pH value of the solution is in acidity.
The method according to the invention, in the freeze drying process, the temperature of the modification is 50~130 DEG C, excellent
Elect 60~80 DEG C as；The time of the modification is 20~240min, preferably 40~80min；In the pasting material solution,
The 0.1~20% of the mass concentration of the hydroaropic substance, preferably 5~15%.
The method according to the invention, the coating processes are comprised the following steps：
By hydroaropic substance dissolving, pasting material solution is obtained；
The pasting material solution is coated on the nano fibrous membrane, and is stood；
The braiding mesh sheet is laid in volatile dry on the pasting material solution, the complex tissue reparation is obtained and is mended
Piece.
The method according to the invention, in the coating processes, the thickness of the pasting material solution is 0.1~3mm, preferably
1~2mm；The time of the standing is 1~72h, preferably 24~48h；In the pasting material solution, the pasting material
Mass concentration is 1~50%, preferably 10~20%.
The method according to the invention, in the coating processes, the hydroaropic substance include protein-based compound and/or
Its derivative, preferably includes one or two in collagen, gelatin；
Preferably, the hydroaropic substance includes the protein-based compound of modified treatment, preferably includes modified place
One or two in collagen, the gelatin of reason.
The method according to the invention, in the coating processes, the modification includes：Carry out being crosslinked instead using crosslinking agent
The step of answering；Preferably, the crosslinking agent is including in carbodiimides/N-hydroxy-succinamide, Geniposide, aldehyde compound
One or more, preferably include carbodiimides, carbodiimides/N-hydroxy-succinamide one or two, it is more excellent
Choosing includes carbodiimides/N-hydroxy-succinamide.
The method according to the invention, in the coating processes, the temperature of the modification is 10~70 DEG C, preferably 25~
50℃；The time of the modification is 1~72h, preferably 12~72h；In the pasting material solution, the hydroaropic substance
Quality 1~50%, preferably 10~20%.
The method according to the invention, the casting technique is comprised the following steps：
By hydroaropic substance dissolving, pasting material solution is obtained；
The braiding mesh sheet is laid on the nano fibrous membrane；
By the pasting material solution curtain coating is in the braiding mesh sheet and stands, volatile dry obtains the complex tissue
Repair sticking patch.
The method according to the invention, in the casting technique, the thickness of the pasting material solution is 0.1~3mm, preferably
1~2mm；The process time of the standing is 1~72h, preferably 24~48h；In the pasting material solution, the pasting material
Mass concentration be 0.1~20%, preferably 5~15%.
The method according to the invention, in the casting technique, the hydroaropic substance include shitosan class compound and/or
Its derivative, preferably includes one or two in carboxymethyl chitosan, hydroxypropyl chitosan；
Preferably, the hydroaropic substance includes the shitosan class compound of modification, preferably includes modified treatment
Carboxymethyl chitosan, hydroxypropyl chitosan in one or two.
The method according to the invention, in the casting technique, the modification includes：Carry out being crosslinked instead using crosslinking agent
The step of answering；Preferably, the crosslinking agent includes glycerine and water；Preferably, the volume ratio of the glycerine and water be 0.1~
5:1, preferably 0.5~2:1.
The method according to the invention, in the casting technique, the temperature of the modification is 10~50 DEG C, preferably 20~
30℃；The time of the modification is 1~48h, preferably 12~24h；In the pasting material solution, the hydroaropic substance
Mass concentration be 0.1~20%, preferably 5~15%.
The present invention also provides a kind of complex tissue of the invention and repairs sticking patch in hernia reparation sticking patch, basin bottom reparation benefit
Piece, urinary incontinence suspender, shoulder sleeve repair the application during sticking patch, breast sticking patch, wound repair sticking patch, fistula repair sticking patch.
The effect of invention
Complex tissue of the invention repairs sticking patch and is difficult layering, there is good mechanical property and flexible nature.
Further, complex tissue of the invention repairs sticking patch and natural extracellular matrix can also be imitated from nanoscale,
The regeneration of cambium and blood vessel as the porous support of cell growth, can be promoted.
In addition, the method for preparing complex tissue reparation sticking patch of the invention is simple, nano fibrous membrane is not interfered with and changed
Original structure, preferably remain the characteristic of the original concrete dynamic modulus tridimensional network of nano fibrous membrane.
Brief description of the drawings
Fig. 1 is the structural representation that the complex tissue that the embodiment of the present invention 1 is prepared repairs sticking patch；
Fig. 2 is the structural representation that the complex tissue that the embodiment of the present invention 2 is prepared repairs sticking patch；
Fig. 3 is that the complex tissue reparation sticking patch prepared using the embodiment of the present invention 2 carries out hernia repair surgery repairing
Photo afterwards；
Fig. 4 is that the complex tissue reparation sticking patch prepared using the embodiment of the present invention 4 carries out hernia repair surgery repairing
Photo afterwards；
Fig. 5 is to carry out the photo after hernia repair surgery repairing using braiding mesh sheet；
Fig. 6 is that the complex tissue reparation sticking patch prepared using embodiment 2 carries out repairing for hernia repair surgery two weeks after
Multiple design sketch；
Fig. 7 is that the complex tissue reparation sticking patch prepared using embodiment 4 carries out repairing for hernia repair surgery two weeks after
Multiple design sketch；
Fig. 8 is the repairing effect figure that hernia repair surgery two weeks after is carried out using braiding mesh sheet.
Specific embodiment
The present invention provides a kind of complex tissue and repairs sticking patch, including：Nano fibrous membrane, braiding mesh sheet and pasting material, its
In, the pasting material is located between the nano fibrous membrane and the braiding mesh sheet.
The pasting material includes hydroaropic substance, preferably includes degradable hydroaropic substance；The nano fibrous membrane
It is combined by the pasting material with the braiding mesh sheet, and the pasting material insertion nanofiber film layer and described
In the hole of mesh grid lamella.
Peel strength between the nano fibrous membrane and the braiding mesh sheet is 20~75cN/mm；The complex tissue
The fracture strength for repairing sticking patch is 8~12.5Mpa；Preferably, the complex tissue repair the extension at break amount of sticking patch for 20~
250%；It is highly preferred that the porosity that the complex tissue repairs sticking patch is 50~90%.
Wherein, the hydroaropic substance can be hydrophilic natural material and/or its derivative, modified treatment it is hydrophilic
Property natural materials and/or its derivative and some hydrophilic non-natural substances etc..By pasting material by nano fibrous membrane
It is effectively compound with braiding mesh sheet, the original structure of nano fibrous membrane and braiding mesh sheet is not interfered with not only, remain Nanowire
The characteristic of dimension film and braiding mesh sheet original structure, additionally it is possible to promotion organization, the reparation of blood vessel and regeneration.
The pasting material is embedded in the hole of the nano fibrous membrane and the braiding mesh sheet, makes nano fibrous membrane and volume
Closely bonding is integrated mesh panel so that the complex tissue for preparing repair sticking patch possess peel strength higher and
Fracture strength, can realize carrying out tissue repair to mechanical strength requirement position higher.
From hydroaropic substance, particularly hydrophilic natural material and/or its derivative and the hydrophily of modified treatment
Natural materials and/or its derivative, can be with fast degradations used as pasting material, additionally it is possible to so that nano fibrous membrane and braiding mesh sheet
Closely bonding is integrated.
Complex tissue of the invention repairs sticking patch, and also including antiblocking layers, the antiblocking layers attach to the volume
On the face opposite with side where nano fibrous membrane of mesh panel.The face opposite with side where nano fibrous membrane of the braiding mesh sheet
Upper its means to weave the one side away from the nano fibrous membrane of mesh sheet.So that the complex repairation sticking patch can not only promote
Enter tissue growth and repair, may also operate as the effect for preventing adhesion, be conducive to preventing complex tissue from repairing sticking patch and internal organs adhesion
And situations such as sticking patch shrinkage, the constant pain or operative site part that can effectively reduce patient lose the complication such as function,
It is that a kind of multi-functional complex tissue repairs sticking patch.
The nano fibrous membrane has the spies such as three-dimensional porous structure, great specific surface area, high porosity and high surface energy
Point, as the porous support of cell growth, can promote migration and the propagation of cell, and the Nanowire with three-dimensional porous structure
Dimension film, it is easier to nutrition and oxygen are conveyed, so that the more conducively propagation of cell and differentiation.
Meanwhile, can further improve the bio-compatible of braiding mesh sheet after mesh sheet surface filming is woven using pasting material
Property.
Complex tissue of the invention repairs sticking patch, wherein, the weight average molecular weight of the hydroaropic substance for 50000~
2000000Da。
Complex tissue of the invention repairs sticking patch, wherein, the hydroaropic substance includes：Containing nitrogen compound and its
Derivative, cellulose compound and its derivative, alcohol compound and its derivative, shitosan class compound and its derivative
One or more in thing, saccharide compound and its derivative；Preferably, it is above-mentioned by one or more after modification
Hydroaropic substance.
Complex tissue of the invention repairs sticking patch, wherein, it is described to include protein-based compound containing nitrogen compound,
Such as：One or two in collagen, gelatin；The shitosan class compound includes：Carboxymethyl chitosan, hydroxypropyl
One or two in sugar；The cellulose compound includes：One kind in carboxymethylcellulose calcium, sodium carboxymethylcellulose or
Two kinds.
Complex tissue of the invention repairs sticking patch, wherein, the distance between the nano fibrous membrane and braiding mesh sheet
It is 0.1~3mm；Preferably 0.2~2mm, that is to say, that the thickness of the pasting material being clipped between nano fibrous membrane and braiding mesh sheet
Degree (not comprising the pasting material inside embedded nano fibrous membrane and braiding mesh sheet) is 0.1~3mm；Preferably 0.2~2mm.Can
With by using measuring instrument (for example：Graduated scale) multiple points (such as 3 points) measure nano fibrous membrane is taken at random with braiding mesh sheet
The distance between obtain.
In general, molecular weight, the thickness of pasting material solution, the pasting material of the thickness of pasting material and pasting material
The factor such as concentration of pasting material is related in solution.For example, when pasting material solution thinner thickness and pasting material is molten
When the concentration of pasting material is relatively low in liquid, the thickness of pasting material is also thinning；When the thickness of pasting material solution is thicker and sticks
When the concentration of pasting material is higher in material solution, the thickness of pasting material is also corresponding thickening.
If nano fibrous membrane is less than 0.1mm with the distance between mesh sheet is woven, pasting material is excessively thin, causes to peel off by force
Degree is slightly worse, influences the composite effect of material；If nano fibrous membrane is more than 3mm with the distance between mesh sheet is woven, stick material
Material is blocked up, so as to the biocompatibility of composite patch and tissue can be influenceed.
In general, the thickness of heretofore described pasting material solution refers both to be clipped in nano fibrous membrane with braiding mesh sheet
Between pasting material solution thickness.
Complex tissue of the invention repairs sticking patch, wherein, the integral thickness that the complex tissue repairs sticking patch is 0.3
~5mm；Preferably 0.5~3mm.
Sticking patch is repaired according to complex tissue of the present invention, wherein, the nano fibrous membrane is used includes electrostatic spinning
Method be obtained, certainly, the nano fibrous membrane can also buy acquisition.
The present invention provides a kind of method of electrostatic spinning, specifically includes following steps：
The degradation material that nano fibrous membrane will be prepared is dissolved in solvent, obtains polymer solution；
Polymer solution is placed in electrostatic spinning syringe, electrostatic spinning is carried out, filament is obtained, and filament is connect
It is membrane structure to receive, and obtains nano fibrous membrane.
Preferably, the solvent includes trifluoroethanol, hexafluoroisopropanol, trifluoroacetic acid, cyclohexanone, acetone, butanone, tetrahydrochysene
One or more in furans, chloroform, glacial acetic acid, formic acid, propionic acid, water.
Preferably, during the electrostatic spinning, the speed for adjusting micro-injection pump is 0.1~15mL/h, and regulation is high
The voltage for pressing generator is 10~35kV, and the reception distance for adjusting reception device is 5~30cm.
Tissue repairing patch of the invention, wherein, the nano fibrous membrane by a diameter of 10nm~100 μm fiber
Silk is interwoven.
Preferably, the degradation material include PLA (PLA), poly (l-lactic acid) (PLLA), PDLLA (PDLLA),
Polycaprolactone (PCL), polyhydroxyalkanoate (PHA), PGA (PGA), poly--lactide (PLGA), collagen is handed over
(Collagen) it is and its derivative, gelatin (Gelatin) and its derivative, shitosan (Chitosan) and its derivative, transparent
One or more in matter acid (HA) and its derivative, cellulose and its derivates.
The tissue repairing patch that prevents adhesion of the invention, wherein, medicine, the medicine are loaded with the nano fibrous membrane
Thing preferably includes growth factor；More preferably include EGF, fibroblast growth factor in one or two.It is multiple
Close tissue repairing patch and can simultaneously serve as a kind of carrier of medicine, drug degradation and loss can be reduced, reduce side effect, carry
High bioavilability.Growth factor refers to that a class is combined by with cell membrane specific receptors, plays regulation cell growth effect
Peptide quasi-molecule, by loading growth factor, enable to repair sticking patch suture by way of, implantation wound tissue when, can
Accelerate cell growth, promote wound healing.
Complex tissue of the invention repairs sticking patch, wherein, the braiding mesh sheet is made up of non-degradable material, preferably
Ground, the non-degradable material includes polypropylene, polyvinylidene fluoride, gathers to the tetracid glycol ester of benzene two, expanded polytetrafluoroethyl-ne
One or more in alkene.
The present invention also provides the preparation method that a kind of complex tissue of the invention repairs sticking patch, including：
Composite steps：Pasting material solution is prepared, the nano fibrous membrane and the braiding mesh sheet are sticked into material described in
Material is solution combined to obtain the complex tissue reparation sticking patch；Preferably, by freeze drying process or coating processes or curtain coating work
With the braiding mesh sheet be combined the nano fibrous membrane with the pasting material solution by skill.
The method according to the invention, wherein, adjust the molecular weight and/or the pasting material solution of the pasting material
Concentration so that the pasting material solution from it is described braiding mesh sheet hole in overflow and it is described braiding mesh sheet and Nanowire
Side where dimension film forms the solution layer that prevents adhesion on opposite face.Preferably, can be by controlling the molecular weight of the pasting material
And/or the concentration of the pasting material solution so that braiding mesh sheet is immersed in pasting material solution, i.e., in the braiding mesh sheet
Form the solution layer that prevents adhesion with the opposite face in side where nano fibrous membrane so that after drying braiding mesh sheet and Nanowire
Side where dimension film forms one layer of Antiadhesive film on opposite surface.
In a kind of specific embodiment, the freeze drying process is comprised the following steps：
By hydroaropic substance dissolving, pasting material solution is obtained；
The pasting material solution is laid in the nano fibrous membrane, and is stood；
The braiding mesh sheet is laid on the pasting material solution, complex tissue reparation benefit is obtained after freeze-drying
Piece.
Preferably, the pasting material solution from it is described braiding mesh sheet hole in overflow and it is described braiding mesh sheet with
Side where nano fibrous membrane forms the solution layer that prevents adhesion on opposite face, complex tissue is obtained after freeze-drying and repairs sticking patch；Make
Obtain the complex tissue and repair sticking patch on the face opposite with side where nano fibrous membrane of the braiding mesh sheet with antiblocking layers.
Preferably, the hydroaropic substance includes cellulose compound and/or radical derivative, preferably includes ethoxy fine
One or more of dimension element, carboxymethylcellulose calcium, hydroxypropyl methyl cellulose；It is highly preferred that the hydroaropic substance includes warp
The cellulose compound of modification/or derivatives thereof；It is further preferred that the hydroaropic substance includes modified treatment
Hydroxyethyl cellulose, carboxymethylcellulose calcium, hydroxypropyl methyl cellulose one or more.
The method according to the invention, wherein, the time of the standing is 1~24h, preferably 3~6h.When pasting material solution
When being laid in the time on the nano fibrous membrane in the range of 1~24h, can preferably make pasting material solution uniform
Nano fibrous membrane surface is distributed in, pasting material solution is embedded into the hole of nano fibrous membrane, between molecule and molecule
Contact area increases, so as to increase the adhesion between pasting material solution and nano fibrous membrane.Preferably, the pasting material
In solution, the mass concentration of the pasting material is 0.1~20%；Preferably 5~15%, the thickness of the pasting material solution
It is 0.1~3mm, preferably 0.2~2mm.
In the present embodiment, the modification includes：The step of cross-linking reaction is carried out using crosslinking agent；Preferably,
The crosslinking agent includes aldehyde compound, one or more in formaldehyde, acetaldehyde, glutaraldehyde is preferably included, more preferably including penta
Dialdehyde.When selecting glutaraldehyde as crosslinking agent in the present invention, the toxicity to organism is relatively small, has during with albumen qualitative response
The advantages of active high, reaction is soon, binding capacity is high, cross-linking properties is good, product is stable.
In the present embodiment, the modification also includes：Cross-linking reaction is carried out in salting liquid；Preferably, it is described
Salt includes neutral salt, and the neutral salt preferably includes one or more in water-soluble aluminum salt, sodium salt, calcium salt and molysite.
The modification is to carry out ground in the solution, and the pH value of the solution is in acidity.
In the present embodiment, the temperature of the modification is 50~130 DEG C, preferably 60~80 DEG C.It is described modified
The time for the treatment of is 20~240min, preferably 40~80min；In the pasting material solution, the quality of the hydroaropic substance
The 0.1~20% of concentration, preferably 5~15%.Preferably, the volume of the crosslinking agent is the 0.1 of the hydroaropic substance quality
~10 volume/mass %, preferably 0.5~5 volume/mass %.In general, the unit of the volume of the crosslinking agent is mL, institute
The unit for stating the quality of hydroaropic substance is g.
In addition, the pre-freezing temperature of the freeze-drying is -80~-10 DEG C, preferably -80~-50 DEG C；Drying temperature is -20
~30 DEG C, preferably -10~25 DEG C.When pre-freezing temperature is between -80~-10 DEG C, porosity higher and more is advantageously formed
Plus homogeneous structure, the specific surface area of material can be increased, so that nanofiber film layer and mesh grid lamella are effectively combined
Together.
In another specific embodiment, the coating processes are comprised the following steps：
By hydroaropic substance dissolving, pasting material solution is obtained；The pasting material solution is uniformly coated in
On the nano fibrous membrane, and stand；
The braiding mesh sheet is laid on the pasting material solution, after volatile dry, the complex tissue is obtained and is repaiied
Multiple sticking patch.
Preferably, the pasting material solution from it is described braiding mesh sheet hole in overflow and it is described braiding mesh sheet with
Side where nano fibrous membrane forms the solution layer that prevents adhesion on opposite face, after volatile dry, obtains the complex tissue reparation and mends
Piece；So that the complex tissue repairs sticking patch on the face opposite with side where nano fibrous membrane of the braiding mesh sheet with anti-sticking
Connect layer.
In the present embodiment, the hydroaropic substance includes protein-based compound and/or its derivative, preferably includes
One or two in collagen, gelatin.It is highly preferred that the hydroaropic substance includes protein-basedization of modified treatment
Compound and/or its derivative.It is further preferred that in collagen, gelatin of the hydroaropic substance including modified treatment
One or two.
Preferably, the thickness of the pasting material solution is 0.1~3mm, preferably 1~2mm；The time of the standing is 1
~72h, preferably 24~48h；In the pasting material solution, the mass concentration of the pasting material is 1~50%, preferably 10
~20%.When pasting material solution is laid in time on the nano fibrous membrane in the range of 1~72h, can be more preferable
The pasting material solution that makes be evenly distributed in nano fibrous membrane surface, pasting material solution is embedded into the hole of nano fibrous membrane
In gap, the contact area increase between molecule and molecule, so as to increase the combination between pasting material solution and nano fibrous membrane
Power.
The crosslinking agent that the modification is used includes carbodiimides/N-hydroxy-succinamide, Geniposide, aldehydes
One or more in compound, preferably include carbodiimides, one kind of carbodiimides/N-hydroxy-succinamide or two
Kind, more preferably including carbodiimides/N-hydroxy-succinamide.
In the present embodiment, the temperature of the modification is 10~70 DEG C, preferably 25~50 DEG C；Modification when
Between be 1~72h, preferably 12~72h；In the pasting material solution, the mass concentration of the hydroaropic substance is 1~50%,
Preferably 10~20%.Preferably, the quality of the crosslinking agent is the 10~50% of the hydroaropic substance quality, preferably 10
~20%.
In another specific embodiment, the casting technique is comprised the following steps：
Hydroaropic substance dissolving is obtained into pasting material solution；
The braiding mesh sheet is laid on the nano fibrous membrane；
The pasting material solution is equably cast in the braiding mesh sheet and stood, obtains described after volatile dry
Complex tissue repairs sticking patch.Preferably, the pasting material solution overflows and in the volume from the hole of the braiding mesh sheet
The solution layer that prevents adhesion is formed on the face opposite with side where nano fibrous membrane of mesh panel, the complex group is obtained after volatile dry
Knit reparation sticking patch.So that complex tissue reparation sticking patch is on the face opposite with side where nano fibrous membrane of the braiding mesh sheet
With antiblocking layers.
Specifically, the hydroaropic substance includes shitosan class compound and/or its derivative, preferably includes carboxymethyl shell
One or two in glycan, hydroxypropyl chitosan.It is highly preferred that the hydroaropic substance includes the shitosan of modified treatment
Class compound and/or its derivative.It is further preferred that the hydroaropic substance includes the carboxymethyl chitosan of modified treatment
Sugar, one or two in hydroxypropyl chitosan.
In the present embodiment, the thickness of the pasting material solution is 0.1~3mm, preferably 1~2mm；The standing
Process time is 1~72h, preferably 24~48h；In the pasting material solution, the mass concentration of pasting material for 0.1~
20%, preferably 5~15%.When between upon standing in the range of 1~72h, can preferably make pasting material solution uniform
Nano fibrous membrane surface is distributed in, pasting material solution is embedded into the hole of nano fibrous membrane, between molecule and molecule
Contact area increases, so as to increase the adhesion between pasting material solution and nano fibrous membrane.
In the present embodiment, the crosslinking agent that the modification is used includes glycerine and water；Preferably, described third
The volume ratio of three alcohol and waters is 0.1~5:1, preferably 0.5~2:1, the hydroaropic substance is directly dissolved in glycerine and water group
Into crosslinking agent in, formed pasting material solution.In the pasting material solution, the mass concentration of the hydroaropic substance is
0.1~20%, preferably 5~15%.The temperature of the modification is 10~50 DEG C, preferably 20~30 DEG C；Modification when
Between be 1~48h, preferably 12~24h.
The pasting material solution that the shitosan class compound is obtained after glycerine and water modification be water white transparency,
Any surface finish, bubble-free.And the complex tissue for finally preparing repairs sticking patch can make the physiological function of wound site
The effect of Synergistic is obtained, and physical and chemical performance can be improved.
In addition, complex tissue reparation sticking patch of the present invention can be three-decker, or sandwich construction, such as four
Rotating fields, five-layer structure etc..When it is five-layer structure that the complex tissue repairs sticking patch, preferably successively by the first nanofiber
Film, the first pasting material, braiding mesh sheet, the second pasting material, the second nano fibrous membrane composition.
The present invention also provides a kind of complex tissue of the invention and repairs sticking patch in hernia reparation sticking patch, basin bottom reparation benefit
Piece, urinary incontinence suspender, shoulder sleeve repair the application during sticking patch, breast sticking patch, wound repair sticking patch, fistula repair sticking patch.
Complex tissue of the invention repairs sticking patch and passes through microcomputer controlled electronic universal material puller system (model HY-3080)
Peel strength δ between test nano fibrous membrane and braiding mesh sheetT.Specific method is：Microcomputer controlled electronic universal material is drawn
Nano fibrous membrane is clamped in power machine one end, and the other end clamps braiding mesh sheet, and it is 25mm to set test gauge, and draw speed is 10mm/
Min, experiment is dimensioned to 50mm × 15mm, and parallel testing 3 times is averaged.Computing formula is：δT=F/ (B × T), wherein,
F is peeling force, and B is testing sample width, and T is the thickness that complex tissue repairs sticking patch.
The assay method that complex tissue of the invention repairs the fracture strength of sticking patch is：By puller system test compound
The fracture strength of tissue repairing patch.Testing sample is cut to the list structure of 40mm × 10mm, is tested out using thickness gauge
Complex tissue repairs the thickness (T) of sticking patch, determines fracture strength (f) and extension at break amount (E), and draw speed is 10mm/min,
Gauge is 25mm, and parallel testing 3 times is averaged.Computing formula is：F=F '/(B × T), wherein, F ' is ultimate strength, and T is
Complex tissue repairs the thickness of sticking patch, and B is testing sample width.
The porosity that complex tissue repairs sticking patch is determined using solvent completion method.Enter complex group because ethanol is readily permeable
Knit without causing Material shrinkage and swelling inside reparation sticking patch, therefore using ethanol as reagent.Specific assay method is as follows：
Inject ethanol solution in the container of 100mL, weigh drying to weight complex tissue repair sticking patch (weight is m1) immersion
In ethanol, circulation is evacuated to complex tissue and repairs sticking patch there is no bubble spilling, weighs and contains ethanol, complex tissue reparation
Sticking patch and beaker gross weight are m2, then by inside, the complex tissue containing ethanol repairs sticking patch taking-up, weighs beaker and residue
Ethanol gross weight be m3, parallel 3 times.Measuring porosity P is：
P=(m2-m3-m1)/(m2-m3) × 100%
Wherein：(m2-m3-m1) quality of the ethanol contained by sticking patch mesopore is repaired for complex tissue；
(m2-m3) it is that the complex tissue containing ethanol repairs sticking patch gross mass.
Embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and should not be taken as limiting the scope of the invention.It is unreceipted specific in embodiment
Condition person, the condition advised according to normal condition or manufacturer is carried out.Agents useful for same or the unreceipted production firm person of instrument, are
Can by city available from conventional products.
Embodiment 1
<The preparation of nano fibrous membrane>
PLA (PLLA) is dissolved in hexafluoroisopropanol solution, wherein, the concentration of PLA is 5% (g/mL), is stirred molten
Solution obtains uniform polymer solution.The polymer solution is placed in electrostatic spinning syringe, regulation micro-injection pump
Speed is 8mL/h, and the voltage for adjusting high pressure generator is 15kV, and the reception distance for adjusting reception device is 15cm, carries out electrostatic
Spinning, electrostatic spinning is closed after thicknesses of layers reaches 0.15mm, obtains nano fibrous membrane.
<The preparation of pasting material solution>
Weigh 20g hydroxyethyl celluloses to be dissolved in 100mL purified waters, add 0.8g calcium chloride, and use second acid-conditioning solution
PH is 4, and stirring and dissolving is uniform；0.8mL glutaraldehyde solutions (mass concentration is 25%) is added, and controlling reaction temperature is 65 DEG C,
Modification 60min；Obtain pasting material solution.
<Complex tissue repairs the preparation of sticking patch>
Nano fibrous membrane is put into container, then above-mentioned pasting material solution is laid on nano fibrous membrane, stood
6h, treats that pasting material solution is evenly embedded into the hole of nano fibrous membrane, and control pasting material solution thickness be 1mm.
Braiding mesh sheet is laid on pasting material solution, the pre-freeze 3h at a temperature of -80 DEG C is then placed in freeze dryer；
36h is dried at 25 DEG C, takes out and prolong molded, obtained complex tissue as shown in Figure 1 and repair sticking patch, wherein, 1 is Nanowire
Dimension film, 2 is braiding mesh sheet, and 3 is pasting material.
Embodiment 2
<The preparation of nano fibrous membrane>
PDLLA (PDLLA) is dissolved in hexafluoroisopropanol solution, wherein, the concentration of PDLLA is 10% (g/
ML), stirring and dissolving obtains uniform polymer solution.The polymer solution is placed in electrostatic spinning syringe, is adjusted micro-
The speed for measuring syringe pump is 7mL/h, and the voltage for adjusting high pressure generator is 20kV, and the reception distance for adjusting reception device is
15cm, carries out electrostatic spinning, and electrostatic spinning is closed after thicknesses of layers reaches 0.2mm, obtains nano fibrous membrane.
<The preparation of pasting material solution>
Weigh 10g sodium carboxymethylcelluloses to be dissolved in 100mL purified waters, add 0.5g calcium chloride, and adjusted with watery hydrochloric acid
PH value of solution is 3, and stirring and dissolving is uniform.0.5mL glutaraldehyde solutions (mass concentration is 25%) is added, and controlling reaction temperature is 70
DEG C, modification 40min.Obtain pasting material solution.
<Complex tissue repairs the preparation of sticking patch>
Nano fibrous membrane is put into container, then above-mentioned pasting material solution is laid on nano fibrous membrane, stood
4h, treats that pasting material solution is evenly embedded into the hole of nano fibrous membrane, and control pasting material solution thickness be 1mm.
Will braiding mesh sheet be laid on pasting material solution, and the pasting material solution from it is described braiding mesh sheet hole
Middle spilling simultaneously forms the solution layer that prevents adhesion on the face opposite with side where nano fibrous membrane of the braiding mesh sheet.It is then placed in
In freeze dryer at a temperature of -80 DEG C pre-freeze 3h；24h is dried at 20 DEG C, takes out and prolong molded, obtain as shown in Figure 2
Complex tissue repairs sticking patch.The complex tissue repairs sticking patch in the opposite with side where nano fibrous membrane of the braiding mesh sheet
There are antiblocking layers on face.Wherein, 1 is nano fibrous membrane, and 2 is braiding mesh sheet, and 3 is pasting material, and 4 is antiblocking layers.
Embodiment 3
<The preparation of nano fibrous membrane>
Gelatin (Gelatin) is dissolved in trifluoroethanol solution, wherein, the concentration of gelatin is 7% (g/mL), and stirring and dissolving is obtained
To uniform polymer solution.The polymer solution is placed in electrostatic spinning syringe, the speed of micro-injection pump is adjusted
It is 5mL/h, the voltage for adjusting high pressure generator is 30kV, the reception distance for adjusting reception device is 20cm, carries out electrostatic spinning,
Electrostatic spinning is closed after thicknesses of layers reaches 0.5mm, nano fibrous membrane is obtained.
<The preparation of pasting material solution>
Weigh 15g sodium hydroxyethyl celluloses to be dissolved in 100mL purified waters, add 1g calcium chloride, and use vinegar acid-conditioning solution
PH is 4, and stirring and dissolving is uniform.The glutaraldehyde solution (25% concentration) of 1mL is added, and controlling reaction temperature is 50 DEG C, be modified place
Reason 60min.Obtain pasting material solution.
<Complex tissue repairs the preparation of sticking patch>
Nano fibrous membrane is put into container, then above-mentioned pasting material solution is laid on nano fibrous membrane, stood
2h, treats that pasting material solution is evenly embedded into the hole of nano fibrous membrane, and controls the thickness of pasting material solution to be
0.5mm。
Will braiding mesh sheet be laid on pasting material solution, and the pasting material solution from it is described braiding mesh sheet hole
Middle spilling simultaneously forms the solution layer that prevents adhesion on the face opposite with side where nano fibrous membrane of the braiding mesh sheet.It is then placed in
In freeze dryer at a temperature of -50 DEG C pre-freeze 4h；24h is dried at 25 DEG C, takes out and prolong molded, obtain complex tissue reparation
Sticking patch.The complex tissue repairs sticking patch on the face opposite with side where nano fibrous membrane of the braiding mesh sheet with anti-sticking
Connect layer.
Embodiment 4
<The preparation of nano fibrous membrane>
PLA (PLA) is dissolved in hexafluoroisopropanol solution, wherein, the concentration of PLA is 7% (g/mL), stirring and dissolving
Obtain uniform polymer solution.Polymer solution is placed in electrostatic spinning syringe, the speed for adjusting micro-injection pump is
15mL/h, the voltage for adjusting high pressure generator is 12kV, and the reception distance for adjusting reception device is 20cm, carries out electrostatic spinning,
Electrostatic spinning is closed after thicknesses of layers reaches 0.3mm, nano fibrous membrane is obtained.
<The preparation of pasting material solution>
Weigh 10g gelatin to be dissolved in 100mL purified waters, be heated to 40 DEG C, stirring obtains uniform gelatin solution.Then plus
Enter 1g carbodiimides/N-hydroxy-succinamide, wherein, carbodiimides is 1 with the mass ratio of N-hydroxy-succinamide:
Modification 48h at 1,25 DEG C, obtains pasting material solution.
<Complex tissue repairs the preparation of sticking patch>
Nano fibrous membrane is put into container, then pasting material solution is coated uniformly on nano fibrous membrane, stood
Time 24h, treats that pasting material solution is evenly embedded into the hole of nano fibrous membrane, and controls the thickness of pasting material solution to be
1mm。
Braiding mesh sheet is laid on pasting material solution, and the pasting material overflows from the hole of the braiding mesh sheet
Go out and form the solution layer that prevents adhesion on the face opposite with side where nano fibrous membrane of the braiding mesh sheet.Under field conditions (factors)
Stand, treat the solvent volatile dry in pasting material solution, obtain complex tissue and repair sticking patch.Complex tissue repairs sticking patch in institute
There are antiblocking layers on the face opposite with side where nano fibrous membrane for stating braiding mesh sheet.
Embodiment 5
<The preparation of nano fibrous membrane>
Poly- second friendship-lactide (PLGA) is dissolved in hexafluoroisopropanol solution, wherein, the concentration of poly- second friendship-lactide is 5%
(g/mL), stirring and dissolving obtains uniform polymer solution.Polymer solution is placed in electrostatic spinning syringe, is adjusted micro
The speed of syringe pump is 10mL/h, and the voltage for adjusting high pressure generator is 25kV, and the reception distance for adjusting reception device is 15cm,
Electrostatic spinning is carried out, electrostatic spinning is closed after thicknesses of layers reaches 0.5mm, obtain nano fibrous membrane.
<The preparation of pasting material solution>
Weigh 20g collagen protein powders to be dissolved in 100mL purified waters, dissolved solution, stirring obtains uniform collagen solution.
3g carbodiimides is subsequently adding, modification 72h at 40 DEG C obtains pasting material solution.
<Complex tissue repairs the preparation of sticking patch>
Nano fibrous membrane is put into container, then pasting material solution is coated uniformly on nano fibrous membrane, stood
Time 36h, treats that pasting material solution is evenly embedded into the hole of nano fibrous membrane, and controls the thickness of pasting material solution to be
2mm。
Braiding mesh sheet is laid on pasting material solution.And the pasting material solution from it is described braiding mesh sheet hole
Middle spilling simultaneously forms the solution layer that prevents adhesion on the face opposite with side where nano fibrous membrane of the braiding mesh sheet.In natural bar
Stood under part, treat the solvent volatile dry in pasting material solution, obtained complex tissue and repair sticking patch.The complex tissue reparation
Sticking patch has antiblocking layers on the face opposite with side where nano fibrous membrane of the braiding mesh sheet.
Embodiment 6
<The preparation of nano fibrous membrane>
Polycaprolactone (PCL) is dissolved in tetrahydrofuran solution, wherein, the concentration of polycaprolactone is 15% (g/mL), stirring
Dissolving obtains uniform polymer solution；Polymer solution is fitted into electrostatic spinning syringe, the speed of micro-injection pump is adjusted
Rate is 6mL/h, and the voltage for adjusting high pressure generator is 20kV, and the reception distance for adjusting reception device is 10cm, carries out Static Spinning
Silk, electrostatic spinning is closed after thicknesses of layers reaches 0.7mm, obtains nano fibrous membrane.
<The preparation of pasting material solution>
5g carboxymethyl chitosans are weighed to be dissolved in the mixed solution of 100mL, wherein, the mixed solution by 50mL purifying
The glycerine composition of water and 50mL, stirring and dissolving obtains uniform chitosan solution.Then at a temperature of 25 DEG C, modification
12h, obtains pasting material solution.
<The preparation of tissue repairing patch>
Nano fibrous membrane is put into container, then braiding mesh sheet is laid on nano fibrous membrane.
By pasting material solution curtain coating in braiding mesh sheet, time of repose 24h, and control the thickness of pasting material solution to exist
1.5mm。
Pasting material solution is penetrated on nano fibrous membrane by weaving the mesh of mesh sheet.And the pasting material is from described
Overflowed in the hole of braiding mesh sheet and formed on the face opposite with side where nano fibrous membrane of the braiding mesh sheet and prevented adhesion
Solution layer.Then under field conditions (factors), the solvent volatile dry in pasting material solution is treated, complex tissue is obtained and is repaired sticking patch.
The complex tissue repairs sticking patch has antiblocking layers on the face opposite with side where nano fibrous membrane of the braiding mesh sheet.
Embodiment 7
<The preparation of nano fibrous membrane>
Hyaluronic acid (HA) is dissolved in water, wherein, the concentration of hyaluronic acid is 3% (g/mL), and stirring is uniformly gathered
Polymer solution；Polymer solution is fitted into electrostatic spinning syringe, the speed for adjusting micro-injection pump is 3mL/h, regulation is high
The voltage for pressing generator is 35kV, and the reception distance for adjusting reception device is 10cm, electrostatic spinning is carried out, when thicknesses of layers reaches
Electrostatic spinning is closed after 0.2mm, nano fibrous membrane is obtained.
<The preparation of pasting material solution>
3g hydroxypropyl chitosans are weighed to be dissolved in the mixed solution of 100mL, wherein, the mixed solution by 50mL purifying
The glycerine composition of water and 50mL, stirring and dissolving obtains uniform chitosan solution.Then at a temperature of 30 DEG C, modification
24h, obtains pasting material solution.
<Complex tissue repairs the preparation of sticking patch>
Nano fibrous membrane is put into container, then braiding mesh sheet is laid on nano fibrous membrane.
By pasting material solution curtain coating in braiding mesh sheet, time of repose 36h, and control the thickness of pasting material solution to exist
2.5mm。
Pasting material solution is penetrated on nano fibrous membrane by weaving the mesh of mesh sheet.And the pasting material is from described
Weave mesh sheet hole in overflow it is described braiding mesh sheet the face opposite with side where nano fibrous membrane on formed prevent adhesion it is molten
Liquid layer.Then under field conditions (factors), the solvent volatile dry in pasting material solution is treated, complex tissue is obtained and is repaired sticking patch.Institute
State complex tissue and repair sticking patch on the face opposite with side where nano fibrous membrane of the braiding mesh sheet with antiblocking layers.
The complex tissue prepared to embodiment 1-7 repairs sticking patch and carries out performance test, as shown in table 1：
Table 1
Hernia reparative experiment
The complex tissue that embodiment 2,4 is prepared repairs sticking patch and carries out hernia reparative experiment.
Take New Zealand's experimental rabbit, 5 months, body weight 2.5kg.New Zealand's experimental rabbit is randomly divided into 3 groups, every group 5 new west
Blue experimental rabbit.New Zealand's experimental rabbit is anaesthetized, preserved skin, is lain on the back and is fixed on plank；After sterilization paving list, hit exactly in belly,
Cut skin along New Zealand experimental rabbit hunter's line with 20# scalpels, be about 10cm, expose muscle, by size be 2cm ×
Stomach wall holostrome (including peritonaeum, the muscle, fascia tissue) excision of 3cm.Be respectively adopted embodiment 2 complex tissue repair sticking patch and
The complex tissue of embodiment 4 repairs sticking patch and commercially available braiding mesh sheet, and with 0# silk threads by sticking patch and the muscle interrupted suture of surrounding,
4# wire discontinuous sewing skins.
As in Figure 3-5, nano fibrous membrane towards abdominal cavity inner side, mesh grid lamella towards outside, wherein, Fig. 3 is use
The complex tissue that the embodiment of the present invention 2 is prepared repairs sticking patch and carries out the photo after hernia repair surgery repairing；Fig. 4 is use
The complex tissue that the embodiment of the present invention 4 is prepared repairs sticking patch and carries out the photo after hernia repair surgery repairing；Fig. 5 is use
Braiding mesh sheet carries out the photo after hernia repair surgery repairing.
It is postoperative that conventional observation and nursing is carried out to New Zealand's experimental rabbit.At postoperative 2 weeks, by the reparation of New Zealand's experimental rabbit
Regional anatomic, the tissue repair situation of observation New Zealand experimental rabbit wound.
Fig. 6 is that the complex tissue reparation sticking patch prepared using embodiment 2 carries out repairing for hernia repair surgery two weeks after
Multiple design sketch；Fig. 7 is that the complex tissue reparation sticking patch prepared using embodiment 4 carries out repairing for hernia repair surgery two weeks after
Multiple design sketch；Fig. 8 is the repairing effect figure that hernia repair surgery two weeks after is carried out using braiding mesh sheet.
Anatomical results show, the complex tissue of embodiment 2,4 repairs newborn substantial amounts of blood vessel and tissue, implantation on sticking patch
It is tightly combined with blood vessel and tissue around position；I.e.：Complex tissue repairs visible substantial amounts of blood vessel and hair within and around sticking patch
Thin blood vessel, shows good tissue repair effect.Therefore, after the complex tissue of implantation embodiment 2,4 repairs sticking patch, newborn group
Knit growth quick, and can grow into during complex tissue repairs sticking patch, repair sticking patch with complex tissue and combine together, and pucker-free is existing
As.And the braiding mesh sheet of control group, during cambium and blood vessel be few, and cambium does not grow into braiding mesh sheet, and have tight
The situation of shrinkage again.
In addition, from Fig. 6-7 as can be seen that the complex tissue reparation sticking patch and histoorgan contact surface of embodiment 2,4 do not have
Any adhesion phenomenon of generation.And from figure 8, it is seen that control group braiding mesh sheet occurs in that many places adhesion with histoorgan.
Therefore, complex tissue of the invention repairs the sticking patch not only function with promotion organization reparative regeneration, and effectively
Serving prevents material shrinkage, prevents internal organs adhesion etc. from acting on, and is that a kind of preferable complex tissue repairs sticking patch.
The above embodiment of the present invention is only intended to clearly illustrate example of the present invention, and is not to the present invention
Implementation method restriction.For those of ordinary skill in the field, can also make on the basis of the above description
The change or variation of other multi-forms.There is no need and unable to be exhaustive to all of implementation method.It is all of the invention
Any modification, equivalent and improvement made within spirit and principle etc., should be included in the protection of the claims in the present invention
Within the scope of.
Claims (31)
1. a kind of complex tissue repairs sticking patch, it is characterised in that the complex tissue repairs sticking patch to be included：
Nano fibrous membrane, braiding mesh sheet and pasting material, wherein, the pasting material is located at the nano fibrous membrane and the volume
Between mesh panel；
The pasting material includes hydroaropic substance, and the nano fibrous membrane and the braiding mesh sheet are by the pasting material phase
With reference to, and the pasting material is embedded into the hole of the nano fibrous membrane and the braiding mesh sheet；
Peel strength between the nano fibrous membrane and the braiding mesh sheet is 20~75cN/mm；The complex tissue reparation
The fracture strength of sticking patch is 8~12.5Mpa；Preferably, the complex tissue repair the extension at break amount of sticking patch for 20~
250%；It is highly preferred that the porosity that the complex tissue repairs sticking patch is 50~90%.
2. complex tissue according to claim 1 repairs sticking patch, it is characterised in that the complex tissue is repaired sticking patch and also wrapped
Antiblocking layers are included, the antiblocking layers are attached on the face opposite with side where nano fibrous membrane of the braiding mesh sheet.
3. complex tissue according to claim 1 and 2 repairs sticking patch, it is characterised in that the weight of the hydroaropic substance is equal
Molecular weight is 50000~2000000Da.
4. the complex tissue according to claim any one of 1-3 repairs sticking patch, it is characterised in that the hydroaropic substance bag
Include：Gather containing nitrogen compound and its derivative, cellulose compound and its derivative, alcohol compound and its derivative, shell
One or more in saccharide compound and its derivative, saccharide compound and its derivative.
5. complex tissue according to claim 4 repairs sticking patch, it is characterised in that described to include albumen containing nitrogen compound
Matter class compound, preferably includes one or two in collagen, gelatin；The shitosan class compound includes：Carboxymethyl
One or two in shitosan, hydroxypropyl chitosan；The cellulose compound includes：Carboxymethylcellulose calcium, carboxymethyl
One or two in sodium cellulosate.
6. the complex tissue according to claim any one of 1-5 repairs sticking patch, it is characterised in that the hydroaropic substance bag
Modified hydroaropic substance is included, the hydroaropic substance for obtaining that is modified by crosslinking agent is preferably included.
7. complex tissue according to claim any one of 1-6 repairs sticking patch, it is characterised in that the nano fibrous membrane with
The distance between braiding mesh sheet is 0.1~3mm；Preferably 0.2~2mm.
8. the complex tissue according to claim any one of 1-7 repairs sticking patch, it is characterised in that the nano fibrous membrane is adopted
It is obtained with the method including electrostatic spinning step.
9. complex tissue according to claim any one of 1-8 repairs sticking patch, it is characterised in that the nano fibrous membrane by
The filament of a diameter of 10nm~100 μm is interwoven, it is preferable that the filament is made up of degradation material, it is highly preferred that
The degradation material includes PLA, PDLLA, polycaprolactone, polyhydroxyalkanoate, PGA, poly- has handed over-the third
Lactide；One or more in collagen, gelatin, shitosan, hyaluronic acid, cellulose.
10. the complex tissue according to claim any one of 1-9 repairs sticking patch, it is characterised in that the nano fibrous membrane
In be loaded with medicine, the medicine preferably includes growth factor；More preferably include EGF, Desmocyte growth factor
One or two in son.
11. complex tissues according to claim any one of 1-10 repair sticking patch, it is characterised in that the braiding mesh sheet by
Non-degradable material is made, it is preferable that the non-degradable material includes polypropylene, polyvinylidene fluoride, gathers to the tetracid of benzene two
One or more in glycol ester, expanded polytetrafluoroethylsealing.
A kind of 12. complex tissues according to claim any one of 1-11 repair the preparation method of sticking patch, it is characterised in that
Including：
Composite steps：Pasting material solution is prepared, the nano fibrous membrane and the braiding mesh sheet is molten with the pasting material
Liquid is compound to obtain the complex tissue reparation sticking patch；
Preferably, using the pasting material solution, by freeze drying process, coating processes or casting technique by the nanometer
Tunica fibrosa is combined with the braiding mesh sheet.
13. methods according to claim 12, it is characterised in that the molecular weight of the adjustment pasting material and/or described
The concentration of pasting material solution so that the pasting material solution overflows and in the braiding from the hole of the braiding mesh sheet
The solution layer that prevents adhesion is formed on the face opposite with side where nano fibrous membrane of mesh sheet.
14. method according to claim 12 or 13, it is characterised in that the freeze drying process is comprised the following steps：
By hydroaropic substance dissolving, pasting material solution is obtained；
The pasting material solution is laid on the nano fibrous membrane, and is stood；
The braiding mesh sheet is laid on the pasting material solution, obtaining the complex tissue reparation by freeze-drying mends
Piece.
15. methods according to claim 14, it is characterised in that the thickness of the pasting material solution is 0.1~3mm,
It is preferred that 0.2~2mm；The time of the standing is 1~24h, preferably 3~6h；In the pasting material solution, the pasting material
Mass concentration be 0.1~20%, preferably 5~15%；Preferably, the pre-freezing temperature of the freeze drying process be -80~-
10 DEG C, preferably -80~-50 DEG C；Drying temperature is -20~30 DEG C, preferably -10~25 DEG C.
16. method according to claims 14 or 15, it is characterised in that the hydroaropic substance includes cellulose family chemical combination
Thing and/or its derivative, preferably include hydroxyethyl cellulose, carboxymethylcellulose calcium, one kind of hydroxypropyl methyl cellulose or several
Kind；Preferably, the hydroaropic substance includes the cellulose compound and/or its derivative of modified treatment, preferably includes
One or more of the hydroxyethyl cellulose of modified treatment, carboxymethylcellulose calcium, hydroxypropyl methyl cellulose.
17. methods according to claim 16, it is characterised in that the modification includes：Handed over using crosslinking agent
The step of connection reaction；Preferably, the crosslinking agent includes aldehyde compound, preferably includes the one kind in formaldehyde, acetaldehyde, glutaraldehyde
Or it is various, more preferably including glutaraldehyde.
18. methods according to claim 17, it is characterised in that the modification also includes：Carried out in salting liquid
Cross-linking reaction；Preferably, the salt includes neutral salt, it is highly preferred that the neutral salt includes water-soluble aluminum salt, sodium salt, calcium salt
With one or more in molysite.
19. method according to claim any one of 16-18, it is characterised in that the modification is to enter in the solution
Capable, it is preferable that the pH value of the solution is in acidity.
20. method according to claim any one of 16-19, it is characterised in that the temperature of the modification be 50~
130 DEG C, preferably 60~80 DEG C；The time of the modification is 20~240min, preferably 40~80min；It is described to stick material
In material solution, the 0.1~20% of the mass concentration of the hydroaropic substance, preferably 5~15%.
21. method according to claim 12 or 13, it is characterised in that the coating processes are comprised the following steps：
By hydroaropic substance dissolving, pasting material solution is obtained；
The pasting material solution is coated on the nano fibrous membrane, and is stood；
The braiding mesh sheet is laid in volatile dry on the pasting material solution, the complex tissue is obtained and is repaired sticking patch.
22. methods according to claim 21, it is characterised in that the thickness of the pasting material solution is 0.1~3mm,
It is preferred that 1~2mm；The time of the standing is 1~72h, preferably 24~48h；It is described to stick material in the pasting material solution
The mass concentration of material is 1~50%, preferably 10~20%.
23. method according to claim 21 or 22, it is characterised in that the hydroaropic substance includes protein-based chemical combination
Thing and/or its derivative, preferably include one or two in collagen, gelatin；
Preferably, the hydroaropic substance includes the protein-based compound of modified treatment, preferably includes modified treatment
One or two in collagen, gelatin.
24. methods according to claim 23, it is characterised in that the modification includes：Handed over using crosslinking agent
The step of connection reaction；Preferably, the crosslinking agent includes carbodiimides/N-hydroxy-succinamide, Geniposide, aldehydes chemical combination
One or more in thing, preferably include carbodiimides, carbodiimides/N-hydroxy-succinamide one or two,
More preferably include carbodiimides/N-hydroxy-succinamide.
25. method according to claim 23 or 24, it is characterised in that the temperature of the modification is 10~70 DEG C,
It is preferred that 25~50 DEG C；The time of the modification is 1~72h, preferably 12~72h；In the pasting material solution, the parent
The 1~50% of the quality of aqueous substance, preferably 10~20%.
26. method according to claim 12 or 13, it is characterised in that the casting technique is comprised the following steps：
By hydroaropic substance dissolving, pasting material solution is obtained；
The braiding mesh sheet is laid on the nano fibrous membrane；
By the pasting material solution curtain coating is in the braiding mesh sheet and stands, volatile dry obtains the complex tissue reparation
Sticking patch.
27. methods according to claim 26, it is characterised in that the thickness of the pasting material solution is 0.1~3mm,
It is preferred that 1~2mm；The process time of the standing is 1~72h, preferably 24~48h；It is described to stick in the pasting material solution
The mass concentration of material is 0.1~20%, preferably 5~15%.
28. method according to claim 26 or 27, it is characterised in that the hydroaropic substance includes shitosan class chemical combination
Thing and/or its derivative, preferably include one or two in carboxymethyl chitosan, hydroxypropyl chitosan；
Preferably, the hydroaropic substance includes the shitosan class compound of modification, preferably includes the carboxylic of modified treatment
One or two in methyl chitosan, hydroxypropyl chitosan.
29. methods according to claim 28, it is characterised in that the modification includes：Handed over using crosslinking agent
The step of connection reaction；Preferably, the crosslinking agent includes glycerine and water；Preferably, the volume ratio of the glycerine and water is
0.1~5:1, preferably 0.5~2:1.
30. method according to claim 28 or 29, it is characterised in that the temperature of the modification is 10~50 DEG C,
It is preferred that 20~30 DEG C；The time of the modification is 1~48h, preferably 12~24h；In the pasting material solution, the parent
The mass concentration of aqueous substance is 0.1~20%, preferably 5~15%.
A kind of 31. complex tissues according to claim any one of 1-11 are repaired sticking patch and are repaiied at hernia reparation sticking patch, basin bottom
Multiple sticking patch, urinary incontinence suspender, shoulder sleeve repair the application during sticking patch, breast sticking patch, wound repair sticking patch, fistula repair sticking patch.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010649423.1A CN111803711B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch prepared by freeze drying process and preparation method thereof |
| CN202010638780.8A CN111803710B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch prepared by tape casting process and preparation method thereof |
| CN202010644114.5A CN111840648B (en) | 2016-12-28 | 2016-12-28 | Multilayer composite tissue repair patch and preparation method thereof |
| CN201611238612.XA CN106693059B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch and preparation method and application thereof |
| CN202010649132.2A CN111840649B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch prepared by coating process and preparation method thereof |
| PCT/CN2017/119133 WO2018121630A1 (en) | 2016-12-28 | 2017-12-27 | Composite tissue repair sheet and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201611238612.XA CN106693059B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch and preparation method and application thereof |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010649132.2A Division CN111840649B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch prepared by coating process and preparation method thereof |
| CN202010644114.5A Division CN111840648B (en) | 2016-12-28 | 2016-12-28 | Multilayer composite tissue repair patch and preparation method thereof |
| CN202010649423.1A Division CN111803711B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch prepared by freeze drying process and preparation method thereof |
| CN202010638780.8A Division CN111803710B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch prepared by tape casting process and preparation method thereof |
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| CN106693059A true CN106693059A (en) | 2017-05-24 |
| CN106693059B CN106693059B (en) | 2020-07-14 |
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| CN202010644114.5A Active CN111840648B (en) | 2016-12-28 | 2016-12-28 | Multilayer composite tissue repair patch and preparation method thereof |
| CN201611238612.XA Active CN106693059B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch and preparation method and application thereof |
| CN202010649132.2A Active CN111840649B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch prepared by coating process and preparation method thereof |
| CN202010638780.8A Active CN111803710B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch prepared by tape casting process and preparation method thereof |
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| CN202010644114.5A Active CN111840648B (en) | 2016-12-28 | 2016-12-28 | Multilayer composite tissue repair patch and preparation method thereof |
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| CN202010638780.8A Active CN111803710B (en) | 2016-12-28 | 2016-12-28 | Composite tissue repair patch prepared by tape casting process and preparation method thereof |
Country Status (2)
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Also Published As
| Publication number | Publication date |
|---|---|
| CN111840649A (en) | 2020-10-30 |
| WO2018121630A1 (en) | 2018-07-05 |
| CN111840648A (en) | 2020-10-30 |
| CN111840649B (en) | 2022-03-29 |
| CN111803711B (en) | 2022-03-29 |
| CN111840648B (en) | 2022-03-25 |
| CN106693059B (en) | 2020-07-14 |
| CN111803710B (en) | 2022-04-19 |
| CN111803710A (en) | 2020-10-23 |
| CN111803711A (en) | 2020-10-23 |
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