CN103800096B

CN103800096B - Pelvic floor dysfunction disease reparation is with implanting fiber diaphragm, preparation method and the medical apparatus and instruments containing it

Info

Publication number: CN103800096B
Application number: CN201210457158.2A
Authority: CN
Inventors: 王国帅; 郭泽跃; 赖奎霖; 徐弢; 袁玉宇
Original assignee: SHENZHEN MEDPRIN REGENERATIVE MEDICAL TECHNOLOGIES Co Ltd
Current assignee: SHENZHEN MEDPRIN REGENERATIVE MEDICAL TECHNOLOGIES Co Ltd
Priority date: 2012-11-14
Filing date: 2012-11-14
Publication date: 2016-12-21
Anticipated expiration: 2032-11-14
Also published as: CN103800096A

Abstract

The present invention provides a kind of tissue repair implantation film for treating female pelvic floor dysfunctional disease, it is characterised in that described implantation film includes fluffy fiber layer (A)；Described fluffy fiber layer (A) is interwoven by the cellosilk of a diameter of 10nm ~ 100 μm, has vesicular texture, and its loft is 400 ~ 1500cm³/ g, its pliability is 50 ~ 500 milli-newton.The most described implantation film farther includes oriented fiber layers (B), and described oriented fiber layers (B) is the layer with cellular three dimensional structure being aligned by cellosilk and being formed.

Description

Pelvic floor dysfunction disease reparation is with implanting fiber diaphragm, preparation method and the medical apparatus and instruments containing it

Technical field

The present invention relates to implantation film, particularly to for treating the implantation film of female pelvic floor dysfunctional disease, preparation method and the medical apparatus and instruments containing it.

Background technology

Being affected by factors such as fertility, disease, agings, the supporting function of pelvic organ is weakened by the soft tissue around pelvic floor, causes various pelvic floor dysfunction disease occur.Pelvic floor dysfunction disease is commonly encountered diseases and the frequently-occurring disease of women.Female pelvic floor functional disorder disease (Pelvic Floor Dysfunction diseas e, PFD), relax also known as pelvic floor defects or pelvic floor supporting tissue, mainly show as the prolapsus of pelvic cavity viscera (such as bladder, uterus, rectum, vagina and small intestinal etc.), bulging (Pelvic OrganProlapse, and stress incontinence (Stress Urinary Incontinence, SUI) POP).POP and SUI is closely related, and life and health on women cause serious impact.It is first-selected currently for moderate and above prolapsus person's operative treatment.Applying pelvic floor patch treatment pelvic floor dysfunction disease in operation, its effect obtains the accreditation of numerous medical personnel and patient.And to use the no-station pole canopy tape surgery managed (including TOT, TVT-O, SPARC, TVT) that carries out of composite medical material be that treatment PFD is most effective at present, method the most thoroughly.

Weak tissue is all reinforced by prothesis repeatedly at the bottom of traditional basin, does not solve root problem, and Postoperative recurrent rate is high, there is the risk again performed the operation.This makes it possible to replace the synthesis of weak impaired pelvic fascia tissue or the biomaterial sticking patch (suspender belt) application in Pelvic pain syndrome more and more extensive.At present in pelvic floor repair product, most widely used is the braiding mesh sheet of synthetic material, and the non-degradable mesh sheet that especially polypropylene material is made occupies overwhelming majority market.But this mesh sheet gradually exposes serious untoward reaction, the problem such as uncomfortable in erosion, exposure, shrinkage, hemorrhage, pain, sexual intercourse.2005-2007, reports the hemorrhage 1000 bad use cases of example, from 2008 to 2010 years, has the 2874 bad reports of example, has caused society and the paying close attention to of FDA.FDA is just advising rising to supervise from implantation II class medical apparatus and instruments by this series products the Group III apparatus of highest level, and has required that relevant manufacturers provides complete clinical report and market to follow the tracks of report.In January, 2012, FDA orders 33 pelvic floor repair sticking patch manufacturers and 7 stress incontinence sticking patch manufacturers carry out product gos deep into clinical research.In June, 2012, Johson & Johnson issues bulletin, ends the first quarter in 2013, it will suspend its company all pelvic floor repair product in the world.The companies such as current J&J, American Me dical Systems, C.R.Bard, Boston Scientific face the lawsuit that up to a hundred relevant issues cause.

Above untoward reaction comes from many-side, mainly due to the sensitivity of female pelvic organs and tissues, weakness (as, vaginal wall is made up of mucosa, muscle layer and fibrous tissue film, vaginal wall is rich in venous plexus, therefore Local Damaged wound is the most hemorrhage or forms hematoma), the material of sticking patch (suspender belt) itself, technique, and modus operandi etc. causes.The mesh sheet quality prepared by knitting skill such as polypropylene material etc. is harder, rough surface, though through the continuous improvement of manufacturer, but still the most thoroughly solve, because this is the limitation of knitting skill itself.This harder, rougher material implants, patient will have more significantly foreign body sensation, and patient there will be material shrinkage, displacement cause the extruding to normal site tissue, friction even puncture, serious complication occurs, as infect, hemorrhage, abnormal flavour, abscess etc..Most common of which is to corrode, and can cause visceral organ injury, material exposure, unbearably pain, affect even threat to life patient's orthobiosis.Also confirming that in later experiments, tissue and the mesh sheet associativity such as polypropylene are the most bad, after taking out mesh sheet, find that tissue and material combine the tightst, it is substantially at the tissue parcel to material, relatively easily tissue and mesh sheet can be peeled off, there is bigger potential safety hazard on long terms.(the Vaginal mesh erosion 7years after a sacral such as clinical discovery corrodes and is generally present in postoperative 12-24 month, Deval Colpopexy, Acta Obstet Gynecol Scand.2003Jul；82 (7): 674-5) once report has mesh sheet to implant the patient occurring mesh sheet to corrode in latter 7 years.This is also that braiding mesh sheet easily occurs shifting the reason causing erosion.

Either corrode or shrinkage, once occur that this problem needs second operation to repair in most cases, or mesh sheet and surrounding infected tissue are thoroughly removed.This will very severely impact the orthobiosis of patient, brings huge wound to the psychology of patient, physiology, and a lot of patients still can not feel well and pain after mesh sheet removes, and affects love life, even cannot normal sitting.

In order to solve the problem of the said goods, prior art (such as CN 101773689A) proposes use electrostatic spinning to replace traditional weaving method to prepare surgery biological patch.Electrostatic spinning is that one prepares polymer superfine fibre simply effective processing method, owing to its superfine fibre prepared can reach nanoscale, nano bionic support can simulate natural extracellular matrix structure to a certain extent effectively, and growth and climbing to cell provide better suited microenvironment.The micro/nano fibrous membrane material that this characteristic makes electrospinning process prepare at present is particularly well-suited to bio-medical field.But, at present in the electrospinning film of research, major part there will be cell and is difficult to slow deficiency of growing in it or grow into, and the mechanical strength of electrospinning film is poor and soft not, is only used for mechanical strength clinically and comfort level requires relatively low position, such as skin etc..

Preferably pelvic floor dysfunction disease reparation implantation film need to possess following performance: the most certain intensity, it is possible to opposing mechanical stress, wants to bear Intraabdominal pressure before health tissues is not fully developed；2. it is easy to cell and tissue sticks, creeps and fast breeding, prevent material from exposing or be subjected to displacement in vivo and rub；3. prevent from antibacterial from hiding to grow, it is to avoid the infection caused because using the braided materials such as polypropylene；4. can keep good dimensional stability after implanting human body, i.e. can not shrink and deform；5. Stability Analysis of Structures, it is simple to be cut into the shape of needs and do not decoherence, it is simple to tissue apposition；The most soft, for repairing at the bottom of basin, it is characterized in the vaginal wall tissue that bottom is thin layer of diaphragm (sticking patch or suspender belt) or is close to urethra, tissue weakness, if the material of diaphragm (sticking patch or suspender belt) is harder, easily causing material and pierce through vaginal wall or the urethra of fragility, cause the complication such as erosion, therefore preferably diaphragm needs have superior pliability；And the pliability that material is suitable for is easy to molding, the operability increasing operation, is reduced the sense of discomfort of patient, the effect of raising operation.But, the performance of the tissue repair fibrous membrane that existing braiding or electrospinning are formed is the most undesirable.

Summary of the invention

The problem that invention is to be solved

The present invention makes in view of above-mentioned problem of the prior art.Purpose is to provide a kind of tissue repair implantation film, it has good mechanical strength, can be to repair premise completely for enough mechanical support, and beneficially cell and the quickly adhesion of tissue and propagation, guiding cell break up, be conducive to fitting tightly between tissue, in combination with preferable diaphragm pliability, the generation of erosion can be effectively reduced or avoided, improve the comfort of patient.

Secondly, the present invention also provides for a kind of tissue repair implantation film, and it has good pliability, good biocompatibility, beneficially tissue are grown into form firm reparation, can have the characteristic of infection, hemostasis further.

For solving the scheme of problem

The present invention relates to a kind of tissue repair implantation film for treating female pelvic floor dysfunctional disease, it is characterised in that described implantation film includes fluffy fiber layer (A)；

Described fluffy fiber layer (A) is interwoven by the cellosilk of a diameter of 10nm ~ 100 μm, has vesicular texture, and its loft is 400 ~ 1500cm³/ g, its pliability is 50 ~ 500 milli-newton.

Implantation film of the present invention, the average pore size of wherein said fluffy fiber layer (A) is 50 ~ 500 μm.

Implantation film of the present invention, the thickness of wherein said fluffy fiber layer (A) is 0.2 ~ 2mm, and tensile strength is 10 ~ 300N/cm.

Implantation film of the present invention, the loft of wherein said fluffy fiber layer (A) is 800 ~ 1300cm³/g。

Implantation film of the present invention, the pliability of wherein said fluffy fiber layer (A) is 200 ~ 450 milli-newton.

Implantation film of the present invention, wherein said fluffy fiber layer (A) uses the method including electrostatic spinning step to prepare.

Implantation film of the present invention, wherein said implantation film farther includes oriented fiber layers (B), and described oriented fiber layers (B) is the layer with cellular three dimensional structure being aligned by cellosilk and being formed.

Implantation film of the present invention, the filametntary a diameter of 10nm in wherein said oriented fiber layers (B)～20 μm.

Implantation film of the present invention, combines between each layer in wherein said implantation film by the way of electrostatic spinning, ultrasonic fusion or stitching.

Implantation film of the present invention, comprises hemostasis class medicine, anti-infection drug, cell growth regulator, toxic inhibitor, anesthetis micro-nano granules and/or the medicine for the treatment of urinary incontinence in wherein said implantation film.

Implantation film of the present invention, the surface of wherein said implantation film comprises hemostatic layer.

Implantation film of the present invention, wherein said hemostatic layer comprises collagen, polyoxyethylene fibre, chitosan, fibrin, peptide and/or thrombin.

Implantation film of the present invention, wherein said hemostatic layer is formed by the method for electrostatic spinning, lyophilization, forced air drying or vacuum drying.

Implantation film of the present invention, the fibrous material of wherein said implantation film is degradation material, non-degradable material or a combination thereof.

Implantation film of the present invention, wherein said degradation material selects one or more in the group of free polylactic acid, polycaprolactone, polyglycolic acid, Poly(D,L-lactide-co-glycolide, Lanthanum Isopropoxide, collagen protein, gelatin, fibrin, fibroin, the peptide polymer of elastin mimicry, chitosan and modification of chitosan composition.

Implantation film of the present invention, one or more in the group of wherein said non-degradable material choosing freely poly-fluorine material, polyolefin, polyurethane, polyamide, polyester and silicone rubber composition.

Implantation film of the present invention, wherein said implantation film has the through hole running through described implantation film upper and lower surface.

Implantation film of the present invention, the aperture of wherein said through hole is 0.2-4mm.

The invention still further relates to the preparation method of described implantation film, it is characterised in that the preparation method of described implantation film includes that the step preparing fluffy fiber layer (A), the described step preparing fluffy fiber layer (A) include:

(1) by two kinds of different for dissolution properties fibrous materials, it is dissolved in respectively in corresponding solvent, obtains the fibrous material solution of both of which one；

(2) the both of which one fibrous material solution obtained in step (1) is respectively charged in different electrostatic spinning syringes, through electrostatic spinning, obtains the fibrous membrane of two kinds of mutual crisscross intersections of the different cellosilk of dissolution properties；

(3) according to the dissolution properties of cellosilk material, being dissolved by a kind of cellosilk in middle for step (2) fibrous membrane manufactured with solvent, another then keeps constant, obtains described fluffy fiber layer (A).

The preparation method of implantation film of the present invention, it is characterised in that the preparation method of described implantation film includes that the step preparing fluffy fiber layer (A), the described step preparing fluffy fiber layer (A) include:

(1) fibrous material is dissolved in solvent, obtains homogeneous fibrous material solution；

(2) the homogeneous fibrous material solution obtained in step (1) is loaded in electrostatic spinning syringe, carry out electrostatic spinning and obtain fiber, and fiber is received as membrane structure, obtain fibrous membrane；

(3) by the fibrous membrane for preparing in step (2) when after solvent supersonic is swelling, carry out pre-freeze, then carry out vacuum lyophilization, obtain described fluffy fiber layer (A).

In above-mentioned preparation method, in described step (3), after the ethanol water that the fibrous membrane concentration prepared is 50 volume % ~ 95 volume % is infiltrated, then carry out ultrasonic swelling in water in step (2).

The preparation method of the implantation film of the present invention, it is characterised in that the preparation method of described implantation film includes that the step preparing fluffy fiber layer (A), the described step preparing fluffy fiber layer (A) include:

(2) the homogeneous fibrous material solution obtained in step (1) is loaded in electrostatic spinning syringe, obtain fibrous membrane through electrostatic spinning；

(3) by the fibrous membrane of preparation in step (2) along the direction stretching of one of the transverse axis of fibrous membrane or the longitudinal axis, after stopping stretching, fibrous membrane is made to shape under this extended state；Then by fibrous membrane along the direction stretching vertical with above-mentioned draw direction of fibrous membrane, make fibrous membrane shape under this extended state after stopping stretching, obtain described fluffy fiber layer (A).

The preparation method of the present invention, the draft temperature wherein stretching described fibrous membrane in step (3) is the temperature less than materials hot deformation temperature 0 DEG C ~ 30 DEG C, and rate of extension is 50 ~ 400mm/min, and tensile elongation is 1.5 ~ 6.0 times of original length, and shaping time is 1h ~ 4h.

Preparation method of the present invention, wherein, described preparation method farther includes to prepare the step of oriented fiber layers (B) with electrostatic spinning.

The invention still further relates to a kind of implanted medical device for treating female pelvic floor dysfunctional disease, it is characterised in that described implanted medical device comprises implantation film of the present invention.

Implanted medical device of the present invention, wherein said implanted medical device is no-station pole canopy urinary incontinence suspender or pelvic floor sticking patch.

Implanted medical device of the present invention, wherein said no-station pole canopy urinary incontinence suspender includes that main part and end, described main part are made up of implantation film of the present invention, and described end is for operating theater instruments traction and/or is used for fixing.

Implanted medical device of the present invention, wherein said main part has straight line or corrugated outline.

Implanted medical device of the present invention, wherein said corrugated concavo-convex stand out is 1mm-5mm.

Implanted medical device of the present invention, wherein said pelvic floor sticking patch includes the middle part bulk portion for repairing the prolapsus of pelvic cavity viscera, bulging, and described middle part bulk portion is made up of implantation film of the present invention.

Implanted medical device of the present invention, wherein said pelvic floor sticking patch includes the arm structure being positioned at bulk portion periphery, middle part for suspending prolapsus pelvic cavity viscera in midair.

The effect of invention

Compared with prior art, there is advantages that

(1) the tissue repair implantation film of the present invention, has bigger serface, and beneficially cell and the quick of tissue adheres to and propagation, and the surface topology of fiber is also beneficial to guide cell differentiation；

(2) the tissue repair implantation film of the present invention has porous fluffy structure, is more beneficial for fibrocyte than the electrospinning membrane structure of common material and grows into rapidly, plays the effect strengthened and fixed；

(3) tissue repair of the present invention improves the general performance of material with implantation film, and quality is light, soft, the requirement that not only laminating female pelvic floor organs and tissues is sensitive, weak, is more conducive to fitting tightly between tissue, improves the comfort of patient；

(4) the tissue repair implantation film of the present invention, it is possible to reduce repair reuse artifacts shrinkage, cause infect and with the generation of the situation such as internal organs adhesion；

(5) the tissue repair implantation film of the present invention, using the teaching of the invention it is possible to provide good biocompatibility, beneficially tissue are grown into form firm reparation, have the characteristic of infection, hemostasis further.

Above beneficial effect, can effectively be reduced or avoided the generation of erosion, it is achieved the preferable reparation to pelvic floor functional disorder disease.

Accompanying drawing explanation

Fig. 1 is fluffy fiber layer (A) the tangent plane scanning electron microscope (SEM) photograph that embodiment 5 obtains；

Fig. 2 is the electrospinning film tangent plane scanning electron microscope (SEM) photograph that embodiment 5 step (2) obtains；

Fig. 3 is an exemplary plot of the no-station pole canopy urinary incontinence suspender of the present invention；

Fig. 4 is another exemplary plot of the no-station pole canopy urinary incontinence suspender of the present invention；

Fig. 5 is the exemplary plot of the pelvic floor sticking patch for forepelvis of the present invention；

Fig. 6 is the exemplary plot of the pelvic floor sticking patch for rear pelvis of the present invention；

Fig. 7 is to dissect design sketch after 4 weeks between IV group of PVDF fluffy fiber layer implantation miniature pig vesicovaginal space in embodiment 9；

Fig. 8 is that in embodiment 9, I group of PP mesh sheet implants between miniature pig vesicovaginal space design sketch after 4 weeks.

Description of reference numerals

1 main part

2 ends

3 outlines

4 through holes

5 sticking patch through holes

Bulk portion in the middle part of 6 sticking patch

The arm structure of 7 sticking patch peripheries

The tractive part of 8 sticking patch arm structures

Detailed description of the invention

The present invention relates to the tissue repair implantation film for treating female pelvic floor dysfunctional disease, described implantation film includes fluffy fiber layer (A)；Described fluffy fiber layer (A) is interwoven by the cellosilk of a diameter of 10nm ~ 100 μm, has vesicular texture, and its loft is 400 ~ 1500cm³/ g, its pliability is 50 ~ 500 milli-newton.The implantation film of the present invention can be single or multiple lift film, when implantation film is monofilm, only includes fluffy fiber layer (A).

When implantation film is multilayer film, one or more layers fluffy fiber layer (A) can be included, the material of other layers, structure, preparation method etc. are not particularly limited, it is possible to use prior art can be used for treating any material, structure and the preparation method of female pelvic floor dysfunctional disease.Preferably, described implantation film may further include oriented fiber layers (B), and described oriented fiber layers (B) is the layer with cellular three dimensional structure being aligned by cellosilk and being formed.Can be combined by modes such as electrostatic spinning, ultrasonic fusion or stitchings between each layer of implantation film.

The fluffy fiber layer (A) of the present invention is interwoven by the cellosilk of a diameter of 10nm ~ 100 μm, has vesicular texture, and its loft is 400 ~ 1500cm³/ g, its pliability is 50 ~ 500 milli-newton.Described filametntary diameter is preferably 500nm ~ 5 μm, and described loft is preferably 800-1300cm³/ g, described pliability is preferably 200 ~ 450 milli-newton.Further, the fluffy fiber layer (A) of the present invention preferably average pore size is 50 ~ 500 μm, preferred thickness be 0.5 ~ 1.0mm, preferably tensile strength be 20 ~ 80N/cm.

Loft of the present invention refers to 1000 times of the apparent thickness of fluffy fiber layer (A) and the ratio of surface density, i.e.

Loft B=apparent thickness T₀/ surface density ω × 10³,

Wherein, loft is with cm³/ g represents, apparent thickness represents with mm, and surface density is with g/m²Represent.Apparent thickness T₀Method of testing be to utilize FAST-1 compressibility Fabric Style instrument to test according to GB/T 7689.1-2001 method, be expressed as fluffy fiber layer (A) at 2cN/cm²Under pressure, thickness (mm) and fluffy fiber layer (A) are at 100cN/cm²The difference of thickness (mm) under pressure.The test mode of surface density ω is under the depth information ignoring fluffy fiber layer (A), measures the weight under single unit are.

Pliability of the present invention refers to the maximum vector sum of frictional force at the counter-bending power of diaphragm that tests out according to method in GB/T 8942-2002 and diaphragm and gap, represents with milli-newton, and softness values the least explanation film is the most soft.

Heretofore described filament diameter is that the method by scanning electron microscope is measured；Described average pore size utilizes Capillary Flow Porosimetry to be measured by Vesicular protein, with reference to ASTM D 6767-2002；Described tensile strength is to be measured by GB/T3923.1-1997 " finished tensile strength and the mensuration of elongation at break " method；Described thickness is measured according to GB/T7689.1-2001 method by compressibility Fabric Style instrument.

As the manufacture method of fluffy fiber layer (A) of the present invention, including using the method including electrostatic spinning step.

As a kind of preferable production process of this fluffy fiber layer (A), electrospinning can be used to combine solvent dissolution method and to carry out, specifically include following steps:

(1) by fibrous materials different for two kinds of dissolution properties, it is dissolved in respectively in corresponding solvent, obtains the fibrous material solution of both of which one；

(2) the both of which one fibrous material solution obtained in step (1) is respectively charged in different electrostatic spinning syringes, the corresponding nozzle needle of two kinds of fibrous materials is evenly distributed on high-tension electricity source plate, carry out electrostatic spinning, obtain the fibrous membrane of two kinds of dissolution properties crisscross intersections of different cellosilks；

(3) according to the dissolution properties of fibrous material, selecting suitable solvent to be dissolved by a kind of cellosilk in the fibrous membrane of preparation in step (2), another then keeps constant, obtains described fluffy fiber layer (A).

In above-mentioned steps (2), the preferably rate adaptation of micro-injection pump is 0.1 ~ 15.0ml/ hour, more preferably 3 ~ 6ml/ hour.The preferably voltage-regulation of high tension generator is 5 ~ 45KV, more preferably 20 ~ 36KV.The receiving range preferably receiving device is adjusted to 5.0 ~ 30.0cm, more preferably 15.0 ~ 20.0cm.

In the present invention, the different fibrous material of the two dissolution properties refers to, in two kinds of fibrous materials, only one of which fibrous material can be dissolved in a certain solvent.A kind of fibrous material preferably wherein is: PCU(polycarbonate polyurethane) or PVDF(Kynoar).Another kind of fibrous material preferably wherein is: PLLA(L-polylactic acid) or PLGA(Poly(D,L-lactide-co-glycolide).

As another preferable production process of the fluffy fiber layer (A) of the present invention, comprise the steps:

(2) the homogeneous fibrous material solution obtained in step (1) is loaded in electrostatic spinning syringe, carry out electrostatic spinning and obtain cellosilk, and cellosilk is received as membrane structure, obtain fibrous membrane；

(3) by the fibrous membrane for preparing in step (2) when after solvent supersonic is swelling, carry out pre-freeze at a predetermined temperature, then carry out vacuum lyophilization, obtain fluffy fiber layer (A).

In above-mentioned steps (2), the preferably rate adaptation of micro-injection pump is 0.1 ~ 15.0ml/ hour, more preferably 3 ~ 6ml/ hour.The preferably voltage-regulation of high tension generator is 5 ~ 45KV, more preferably 30 ~ 36KV.The receiving range preferably receiving device is adjusted to 5.0 ~ 30.0cm, more preferably 15.0 ~ 20.0cm.

In above-mentioned steps (3), the solvent for ultrasonic swollen fiber film is preferably water for injection.After preferably the ethanol water that the fibrous membrane concentration prepared in step (2) is 50 volume % ~ 95 volume % being infiltrated, put in the ultrasonic machine filling water for injection, stand after ultrasonic swelling 5 ~ 15 minutes, change water for injection, the most ultrasonic swelling, it is replaced until ethanol is injected with water.Then the fibrous membrane under ultrasonic for water for injection swelling rear state is put in freeze drying box and carry out precooling 2 ~ 5 hours in-50 DEG C, be then turned on vacuum and carry out vacuum lyophilization 20 ~ 26 hours, obtain described fluffy fiber layer (A).

(3) by the fibrous membrane of preparation in step (2) along the direction stretching of one of the transverse axis of fibrous membrane or the longitudinal axis, after stopping stretching, fibrous membrane is made to shape under this extended state；Then by fibrous membrane along the direction stretching vertical with above-mentioned draw direction of fibrous membrane, make fibrous membrane shape under this extended state after stopping stretching, obtain fluffy fiber layer (A).

In above-mentioned steps (3), horizontal and vertical rate of extension is preferably each independently 50 ~ 400mm/min, more preferably 50mm/min ~ 200mm/min.Horizontal and vertical tensile elongation is preferably each independently 1.5 ~ 6.0 times of original length.

nullIn above-mentioned steps (3)，Preferably，The both sides of the fibrous membrane prepared in above-mentioned steps (2) are lived with clip，Temperature is set below the temperature of fibrous material heat distortion temperature 0 DEG C ~ 30 DEG C，At the uniform velocity stretch with the speed of 50 ~ 400mm/min，Fibrous membrane is made to stop stretching after being elongated to 1.5 ~ 6.0 times of original length，Fibrous membrane is made to shape under this extended state 1h ~ 4h at normal temperatures，Then take off and the other both sides fixture of fibrous membrane is clamped，Temperature is set below the temperature of materials hot deformation temperature 0 DEG C ~ 30 DEG C，At the uniform velocity stretch along the direction vertical with draw direction before with the speed of 50 ~ 400mm/min，Fibrous membrane is made to stop stretching after being elongated to 1.5 ~ 6.0 times of original length，Fibrous membrane is made to shape under this extended state 1h ~ 4h at normal temperatures，Obtain fluffy fiber layer (A).

Fig. 1 is the tangent plane Electronic Speculum figure of the fluffy fiber layer (A) obtained according to said method in the embodiment of the present invention 5, Fig. 2 be in the embodiment of the present invention 5 according to said method after step (2), the electrospinning film obtained.Shown in Fig. 1 and Fig. 2, it can be seen that the fluffy fiber layer (A) of the present invention and the electrospinning film that common electrospinning obtains are different on the fibre structure of microcosmic, and are macroscopically showing as the difference such as loft, pliability, by 130cm³The loft of/g and the pliability of 870 milli-newton become 1100cm³The loft of/g and the pliability of 400 milli-newton.The fluffy fiber layer (A) of the visible present invention has more preferable bulkiness and flexibility.

Oriented fiber layers (B) is the layer with cellular three dimensional structure being aligned by the cellosilk of a diameter of 10nm～20 μm and being formed.It has regular fiber orientation, the arrangement of collagen fibers direction in Muscle membrane extracellular matrix can be simulated, cell can be guided to grow, extracellular matrix for cell and new secretion thereof provides orientation skeleton, the organizational structure of body self is imitated as far as possible from structure, being very beneficial to growing into of fibroblast and blood capillary, the self-regeneration to muscle, fascia plays a key effect, repairing effect stable when can realize long.Such that it is able to realize preferable postoperative repairing effect, reduce relapse rate.

Electrostatic spinning is preferably used in the present invention and prepares oriented fiber layers (B), its operating condition be regulation micro-injection pump speed be 0.1～15.0 ml/hour, the voltage of regulation high tension generator is 5～45kV, it is 5.0～30.0 centimetres that regulation receives the receiving range of device, regulation electrospinning syringe needle translational speed 1～20 cel, receiving roll rotating speed be 2000～6000 circle/point.

The material of the implantation film of the present invention includes non-degradable material, degradation material or its combination.Described non-degradable material mainly includes poly-fluorine class material, such as polyvinylidene fluoride (PVDF), polytetrafluoroethylene (PTFE) etc.；Polyolefin, such as polyethylene, polypropylene etc.；Polyurethane material, such as polyurethanes (PU), polycarbonate polyurethane (PCU), polyether based polyurethanes, silicane-modified polyurethane (SPU) etc..Described degradation material mainly includes the synthetic materials such as polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), Poly(D,L-lactide-co-glycolide (PLGA), 1,3-glycol polymers (PDO)；With collagen protein, gelatin, fibrin, fibroin, the natural macromolecular material such as peptide polymer of elastin mimicry；Chitosan, modification of chitosan.The fibrous material that fluffy fiber layer (A), oriented fiber layers (B) and other layer use can be identical or different, wherein, oriented fiber layers (B) prepared by preferably polyvinylidene fluoride material, and it has good histocompatibility and durability, and mechanical strength is good.Preferably polyvinylidene fluoride (PVDF), polycarbonate polyurethane (PCU), polylactic acid (PLA) prepares fluffy fiber layer (A).

The implantation film of the present invention can also be containing the layer beyond fluffy fiber layer (A) and oriented fiber layers (B), and it can be the fibrous layer (C) of No yield point prepared by common electrospinning, woven mesh layer (D) or memory metal layer (E).

The implantation film of the present invention can also be containing comprising anti-infection drug, hemostasis class medicine and/or the layer of micro-nano granules, wherein said anti-infection drug, hemostasis class medicine and/or micro-nano granules may be located in the fibrous layer (C) of fluffy fiber layer (A), oriented fiber layers (B), No yield point, other layer outside above layers can also be positioned at, it is also possible to be adsorbed in the surface of implantation film.

Described anti-infection drug includes ampicillin class, spiramycin class, sulfonamides, quinolones and/or cephalosporins.Described hemostasis class medicine includes 6-aminocaprolc acid, para-amino-methyl-benzoic acid, tranamic acid, Radix Notoginseng and/or YUNNAN BAIYAO.Described micro-nano granules includes SiO₂、TiO₂, ZnO, Ag, Ni, quaternary ammonium salt, chitosan, calcium alginate, polyvinyl alcohol and/or the nanoparticle of natural macromolecular.

The implantation film of the present invention can be modified further across post processing, such as, can process through the mode of one or more in drilling process, hyperthermic treatment and immersion treatment.Described fibrous membrane can also carry out sewing process with tinsel or polymer fiber.

Described drilling processes and punching press drilling, laser punching, local pressure can be used to found the methods such as hole to form the through hole of perforating fiber film upper and lower surface.Wherein preferred laser punching, by regulation and parameters optimization, after cut pore-forming, hole periphery can be become compact texture by a high temperature moment melted part, and the width of hole periphery puddle is about 0.02 ~ 0.05mm.This puddle can play fixation holes size, maintains the effect of product entirety mechanical property.When using electrostatic spinning preparation to implant sticking patch, can receive plate by using metal, insulation staggered-mesh, the Coulomb repulsion lines receiving strip tool patterning carrys out drilling.

Repair system research at the bottom of long-term basin shows, the aperture of implantation film is most important to therapeutic effect.And brace aperture rate height prepared by conventional electrospinning process, but aperture is the least；And the mechanical property of general forming hole method meeting extreme influence electrospun scaffold.The present invention is by research and relatively more different aftertreatment technologys, and through the most external, vivo biodistribution experiment, show that mechanical strength is good, more soft and the preferable diaphragm material of therapeutic effect through repeatedly optimizing, possesses suitable pore size and hole arranges.Grow into as used the mode that the hole of certain size is staggered or different size hole combines can preferably be beneficial to tissue, improving inside and outside material while exchange, be also beneficial to the quick eliminating of metabolite when tissue, cell growth.Meanwhile, hole provides penetrating of more spaces, more conducively blood capillary for tissue growth.

In order to keep mechanical strength, can prepare in the way of combining to use macropore and aperture: stamp the macropore of 0.8～1.6mm diameter according to 0.5～1cm spacing；2～4 0.4～the aperture of 0.6mm diameter is uniformly stamped between every four macropores.Increase pore quantity while so can keeping patch mechanical strength, be more conducive to organize quick through growth.

The implanted medical device for treating female pelvic floor dysfunctional disease of the present invention, comprises the implantation film of the present invention.Concrete, described implanted medical device can be no-station pole canopy urinary incontinence suspender or pelvic floor repair sticking patch.

Described no-station pole canopy urinary incontinence suspender (hereinafter referred to as suspender belt), including main part and end, described main part is made up of the implantation film of the present invention, and described end is for operating theater instruments traction and/or is used for fixing.

Exemplarily, the suspender belt of the present invention can have the outward appearance such as Fig. 3-4, suspender belt includes main part 1 and end 2, after suspender belt implants human body, main part 1 contacts with anterior vaginal wall and urethra interbed, main part 1 embeds obturator fascia and makes it keep tensioning state thus to urethra applying support force upwards, and end 2 is drawn for operating theater instruments and/or is used for fixing.Suspender belt width is preferably 5mm-30mm, and thickness is preferably 0.1mm-2mm.The main part of suspender belt can have straight line (such as Fig. 3) or the outline 3 of corrugated (such as Fig. 4), and described corrugated concavo-convex stand out is preferably 1mm-5mm.End can also have corrugated outline same or analogous with main part in a specific embodiment.The suspender belt with corrugated outline is preferably used, and it can make more firm being fixed among pelvis obturator membrane of suspender belt.Preferably, the main part 1 of suspender belt having the through hole 4 of a diameter of 0.1mm-3mm, it runs through the upper and lower surface of suspender belt main part, is conducive to tissue to grow between hole, plays the effect of further grappling mesh sheet.A diameter of 1.2mm-3mm of the most described through hole 4.

Described pelvic floor sticking patch includes that described mid-section body part is made up of the implantation film of the present invention for repairing the prolapsus of pelvic cavity viscera (such as bladder, uterus, rectum, vagina and small intestinal etc.), the mid-section body part of bulging.The implantation film used in described pelvic floor sticking patch preferably comprises oriented fiber layers (B).Exemplarily, the pelvic floor sticking patch of the present invention can be for if Fig. 5 (for forepelvis) and 6(is for rear pelvis) shown in shape, described pelvic floor sticking patch includes being positioned at middle part the bulk portion 6 and arm structure 7 of periphery for suspend prolapsus pelvic cavity viscera in midair, the end of described arm structure 7 is the tractive part 8 of arm structure, preferably has the through hole 5 running through upper and lower surface on the middle part bulk portion 6 of sticking patch and the arm structure 7 of periphery.Described middle part bulk portion 6 is adjusted according to the shape of the pelvic cavity viscera for repairing, and the shape of arm structure 7 and quantity can also specifically be adjusted according to internal organs to be repaired.

The implanted medical device being made up of the implantation film of the present invention may be used for the treatment of female pelvic floor functional disorder disease.The no-station pole canopy urinary incontinence suspender of the present invention may be used for the treatment of female incontinence, and pelvic floor sticking patch may be used for repairing the prolapsus of pelvic cavity viscera, bulging.

Embodiment

Embodiment 1

(1) polyvinylidene fluoride (PVDF) is dissolved in the mixed solvent of DMF/acetone that volume ratio is 4:6, and making PVDF concentration in the solution is 18g/100mL, obtains homogeneous fibrous material solution A；Being dissolved in hexafluoroisopropanol (HFIP) solution by PLLA (PLLA), making the concentration of PLLA in solution is 5g/100mL, obtains homogeneous fibrous material solution B.

(2) fibrous material solution A homogeneous for above two and B are respectively charged in five electrostatic spinning syringes, wherein 4 syringe dress PVDF solution, a syringe dress PLLA solution.1 nozzle needle that 4 nozzle needles that PVDF solution is corresponding are corresponding with PLLA is evenly distributed on high-tension electricity source plate, the speed of regulation micro-injection pump is 5mL/ hour, the voltage of regulation high tension generator is 30KV, it is 25cm that regulation receives the receiving range of device, prepared the fibrous membrane of two kinds of different crisscross intersections of cellosilk material of dissolution properties by electrostatic cospinning while bi-material, after reaching 0.5mm thickness, stop electrostatic spinning.

(3) film that will take off, put in hexafluoroisopropanol solvent ultrasonic swelling, dissolve 6 hours so that it is middle PLLA material is completely dissolved, prepare fluffy fiber layer (A1).

The average fibre diameter of described fluffy fiber layer (A1) is 3 μm, and film thickness is 0.5mm, and average pore size is 350 μm, and tensile strength is 60N/cm, and loft is 420cm³/ g, pliability is 470 milli-newton.

Embodiment 2

(1) PVDF material being dissolved in DMF/acetone mixed solvent that volume ratio is 4:6, making PVDF concentration in the solution is 20g/100mL；Prepare homogeneous fibrous material solution.

(2) the fibrous material solution obtained in step (1) is loaded in electrostatic spinning syringe, the speed of regulation micro-injection pump is 6mL/ hour, the voltage of regulation high tension generator is 30KV, it is 25cm that regulation receives the receiving range of device, carry out electrostatic spinning and obtain cellosilk, and cellosilk is received as membrane structure, spin stopping electrostatic spinning after being about 0.5mm to thicknesses of layers, obtain fibrous membrane.

The average fibre diameter of the fibrous membrane herein obtained is 2 μm, and film thickness is 0.5mm, and average pore size is 150 μm, and tensile strength is 32N/cm, and loft is 110cm³/ g, pliability is 740 milli-newton.

(3) the fibrous membrane complete wetting in the ethanol solution that concentration is 95 volume % that will prepare in step (2), then takes out the fibrous membrane after ethanol solution infiltration, puts in the ultrasonic container filling water for injection, make fibrous membrane be fully immersed in water for injection, open ultrasonic, power 90W, ultrasonic 10 minutes, after standing 5 ~ 10 minutes, change the water for injection in ultrasonic container, be then turned on ultrasonic, power 90W, ultrasonic 10 minutes, repeating operation 7 ~ 8 times, to solution, ethanol is replaced complete.Then take out water for injection ultrasonic swelling after fibrous membrane, be put in the freeze drying box of-50 DEG C and carry out precooling 4 hours, be then turned on vacuum lyophilization, make the fibrous membrane vacuum lyophilization 24 hours of precooling, obtain fluffy fiber layer (A2).

The average fibre diameter of described fluffy fiber layer (A2) is 2 μm, and film thickness is 0.6mm, and average pore size is 380 μm, and tensile strength is 37N/cm, and loft is 1105cm³/ g, pliability is 400 milli-newton.

Embodiment 3

(1) PVDF material being dissolved in DMF/acetone mixed solvent that volume ratio is 4:6, making PVDF concentration in the solution is 18g/100mL；Prepare homogeneous fibrous material solution；

(2) the fibrous material solution obtained in step (1) is loaded in electrostatic spinning syringe, the speed of regulation micro-injection pump is 6mL/ hour, the voltage of regulation high tension generator is 30KV, it is 20cm that regulation receives the receiving range of device, carry out electrostatic spinning and obtain cellosilk, and cellosilk is received as membrane structure, spin stopping electrostatic spinning after being about 0.5mm to thicknesses of layers, obtain fibrous membrane.

The average fibre diameter of the fibrous membrane herein obtained is 2 μm, and film thickness is 0.5mm, and average pore size is 190 μm, and tensile strength is 43N/cm, and loft is 170cm³/ g, pliability is 930 milli-newton.

(3) both sides of fibrous membrane are then clamped with fixture, under the conditions of temperature is 95 DEG C, the speed with 100mm/min at the uniform velocity stretches, fibrous membrane is made to stop stretching after being elongated to 3.0 times of original length, fibrous membrane is made to shape under this extended state 4h at normal temperatures, then take off fibrous membrane and clamp the other both sides of fibrous membrane with fixture, under the conditions of temperature is 95 DEG C, at the uniform velocity stretch along the direction vertical with draw direction before with the speed of 100mm/min, fibrous membrane is made to stop stretching after being elongated to 3.0 times of original length, fibrous membrane is made to shape under this extended state 4h at normal temperatures, obtain fluffy fiber layer (A3).

The average fibre diameter of described fluffy fiber layer (A3) is 2 μm, and film thickness is 0.6mm, and average pore size is 400 μm, and tensile strength is 65N/cm, and loft is 1410cm³/ g, pliability is 400 milli-newton.

Embodiment 4

(1) by polycarbonate polyurethane (PCU), it is dissolved in the mixed solvent of DMF and oxolane, making the concentration of PCU in solution is 12g/100mL, DMF is 1:1 with the mixed proportion (volume ratio) of oxolane, obtains homogeneous fibrous material solution A.

Being dissolved in by PLLA in hexafluoroisopropanol (HFIP) solution, making the concentration of PLLA in solution is 5g/100mL, obtains homogeneous fibrous material solution B.

(2) fibrous material solution A homogeneous for above two and B are respectively charged in 4 electrostatic spinning syringes, wherein 3 syringe dress PCU solution, a syringe dress PLLA solution.1 nozzle needle that 3 nozzle needles that PCU solution is corresponding are corresponding with PLLA is evenly distributed on high-tension electricity source plate, the speed of regulation micro-injection pump is 6mL/ hour, the voltage of regulation high tension generator is 28KV, it is 22cm that regulation receives the receiving range of device, prepared the fibrous membrane of two kinds of different crisscross intersections of cellosilk material of dissolution properties by electrostatic cospinning while bi-material, after reaching 0.5mm thickness, stop electrostatic spinning.

(3) film that will take off, put in hexafluoroisopropanol solvent ultrasonic swelling, dissolve 6 hours, make PLLA material dissolve completely, PCU material then keeps constant, takes out the material not being dissolved, i.e. obtain fluffy fiber layer (A4) from solvent.

The average fibre diameter of gained fluffy fiber layer (A4) is 2 μm herein, and film thickness is 0.5mm, and average pore size is 300 μm, and tensile strength is 25N/cm, and loft is 830cm³/ g, pliability is 230 milli-newton.

Embodiment 5

(1) being dissolved in hexafluoroisopropanol solvent by PLLA (PLLA) material, making PLLA concentration in solution is 6g/100mL, prepares homogeneous fibrous material solution.

(2) the fibrous material solution prepared in step (1) is loaded in electrostatic spinning syringe, the speed of regulation micro-injection pump is 6mL/ hour, the voltage of regulation high tension generator is 20KV, it is 15cm that regulation receives the receiving range of device, carry out electrostatic spinning and obtain cellosilk, and cellosilk is accepted as membrane structure, spin stopping electrostatic spinning after being about 0.5mm to thicknesses of layers, obtain fibrous membrane.

The average fibre diameter of the fibrous membrane herein obtained is 2 μm, and film thickness is 0.5mm, and average pore size is 115 μm, and tensile strength is 33N/cm, and loft is 130cm³/ g, pliability is 870 milli-newton.

(3) both sides of fibrous membrane are then clamped with fixture, under the conditions of temperature is 60 DEG C, the speed with 100mm/min at the uniform velocity stretches, fibrous membrane is made to stop stretching after being elongated to 3 times of original length, fibrous membrane is made to shape under this extended state 4h at normal temperatures, then take off fibrous membrane and clamp the other both sides of fibrous membrane with fixture, under the conditions of temperature is 60 DEG C, at the uniform velocity stretch along the direction vertical with draw direction before with the speed of 100mm/min, fibrous membrane is made to stop stretching after being elongated to 3 times of original length, fibrous membrane is made to shape under this extended state 4h at normal temperatures, obtain fluffy fiber layer (A5).

The average fibre diameter of described fluffy fiber layer (A5) is 2 μm, and film thickness is 0.6mm, and average pore size is 450 μm, and tensile strength is 50N/cm, and loft is 1100cm³/ g, pliability is 400 milli-newton.

Embodiment 6

PVDF material is dissolved in DMF/acetone mixed solvent that volume ratio is 4:6, and making PVDF concentration in the solution is 20g/100mL；Prepare homogeneous fibrous material solution.

The fluffy fiber layer (A2) embodiment 2 prepared covers on receiving roll surface, aforementioned PVDF solution is loaded in electrostatic spinning syringe, the speed of regulation micro-injection pump is 4mL/ hour, the voltage of regulation high tension generator is 28KV, it is 20cm that regulation receives the receiving range of device, translational speed 10 cel of electrospinning syringe needle, receiving roll rotating speed be 4000 circles/point, carry out electrostatic spinning, fluffy fiber layer (A2) is formed oriented fiber layers (B1), thus obtains comprising fluffy fiber layer (A2) and the double layer fibre film of oriented fiber layers (B1).

Embodiment 7

Previous solu is loaded in electrostatic spinning syringe, the speed of regulation micro-injection pump is 4mL/ hour, the voltage of regulation high tension generator is 28KV, it is 20cm that regulation receives the receiving range of device, translational speed 10 cel of electrospinning syringe needle, receiving roll rotating speed be 4000 circles/point, carry out electrostatic spinning.Spin closedown electrostatic spinning after being about 0.3mm to thicknesses of layers, obtain the oriented fiber layers (B2) of orderly aligned single-layer.

(2) two kinds of fibrous membranes of fluffy fiber layer (A3) prepared by the oriented fiber layers (B2) of step (1) and embodiment 3 are stacked together, then 20000Hz frequency ultrasound (Fu Tan plant equipment company limited is used, model JT-200-S), by the way of putting ultrasonic fusion, above layers is linked together every the distances of 10 centimetres, obtain comprising fluffy fiber layer (A3) and the double layer fibre film of oriented fiber layers (B2).

Embodiment 8

By 0.9g sodium chloride, 1.79g 12 Heshui disodium hydrogen phosphate is dissolved in 70mL aqueous solution, after fully dissolving, adds acetic acid solution that 1.5mL concentration is 36 volume % and 20mL ethanol stirs, obtain solution A.

By the II Collagen Type VI heating for dissolving of 2g oxidized cellulose and 2g in above-mentioned solution A, and treat that it cools down, obtain solution B.

The thrombin lyophilized powder of lyophilizing is made concentration is 350 units/mL, the thrombin solution of 10mL is joined B in above-mentioned solution, obtains solution C.

The fluffy fiber layer (A 1-5) prepared in embodiment 1,2,3,4,5 is immersed in above-mentioned solution C 10 minutes, the diaphragm fully soaked is carried out lyophilizing overnight.It is cropped to the specification needed, obtains one containing repairing diaphragm and no-station pole canopy suspender at the bottom of the basin of hemostatic function composition oxidized cellulose.

Embodiment 9

Use the existing clinical polypropylene mesh (3DMAX used^TMnullMesh，The sample provided by No.2 Hospital Attached to Zhongshan Univ) as a control group (I group)、The fibrous membrane (II group) as a control group obtained is reduced by the electrospinning film prepared in embodiment 1 step (2)、The implantation film 1(III group obtained is reduced) by PVDF fluffy fiber layer (A1) prepared in embodiment 1、PVDF fluffy fiber layer (A2) prepared by embodiment 2 reduces the implantation film 2(IV group obtained)、PVDF fluffy fiber layer (A3) prepared by embodiment 3 reduces the implantation film 3(V group obtained)、PCU fluffy fiber layer (A4) prepared by embodiment 4 reduces the implantation film 4(VI group obtained)、PLLA fluffy fiber layer (A5) prepared by embodiment 5 reduces the implantation film 5(VII group obtained) carry out miniature pig experiment as experimental group.Above-mentioned material is all cut into 2cm × 2cm size diaphragm.Select 20kg～25kg, health adult female miniature pig 28, be randomly divided into 7 groups, often group 4.

Miniature pig is implemented general anesthesia, faces upward Baoding.Through hypogastric region stomach wall approach, expose bladder, uterus and vagina epimere.Being respectively implanted between vesicovaginal space by diaphragm, silk thread is fixed.The postoperative nursing that animal is carried out routine and observation.In all laboratory animal observation periods, all performance is good, and wound healing is good, and, exposure prominent without implant etc. occurs, and art portion is without redness.Postoperative and the mental status are normal, give enough spaces for activities, all to survive to the time of drawing materials.

Postoperative 4 weeks, often group put to death two animals, cut include the vesicovaginal space tissue specimen repaired including sticking patch.Touch the pliability of embedded material with hands, the polypropylene mesh that contrast groups is I group is the most hardening, has foreign body sensation；II group of pliability of contrast groups is taken second place, and experimental group sticking patch pliability all has greatly improved, and specifically, optimum with IV, V, VII group of pliability, flexible, close to autologous tissue.

Tissue within contrast material grow into situation and with new tissue growth situation around, gross examination of skeletal muscle, the tissue of experimental group (III-VII) diaphragm is grown into situation and more excellent compared with I group of polypropylene mesh and II group of diaphragm of contrast groups with the degree of being firmly combined with of cambium around, show as experimental group membrane surface and all cover one layer of newborn epithelial tissue, vascularization degree is higher, diaphragm and cambium not easily openable；Dissection effect such as Fig. 7 after 4 weeks after wherein IV group of PVDF material is implanted, it is seen that implant site cambium and surrounding tissue zero difference.I group of polypropylene mesh and II group of membrane surface of contrast groups are again covered with one layer of cambium, but the capillary tube on cambium is sparse；And I group of polypropylene mesh easily peel off with sticking patch, such as Fig. 8, being still the harder rack of quality after material and cambium stripping, new life does not grow into；Effect that visible experimental group has a more preferable cell and tissue is grown into, the compatibility and laminating ability with cambium are stronger.

Pathological examination shows, all there are a large amount of fibroblast and collagen fiber hyperplasia in III-VII group implantation film surface and inside, has more blood capillary (3-5/HPF) inside sticking patch；Wherein, there is a large amount of blood capillary (5-10/HPF) inside V group of sticking patch.Visible cambium has been grown into inside diaphragm, and vascularization degree is high, and it is very fast to grow into, and quickly growing into that cell is creeped, breeds and organized by higher loft is more favourable.II group of fiber membrane surface has more fibroblast and collagen fiber, the internal visible a small amount of fibroblast of sticking patch and collagen fiber hyperplasia, minority lymphocytic infiltration (< 5/HPF), a small amount of blood capillary proliferation (2-3/HPF), visible cambium diaphragm of growing into is internal but grow into relatively slow, and has slight immunization inflammatory reaction.Substantial amounts of fibroblast and collagen is had around I group of polypropylene networking sheet, small amount blood capillary (< 2/HPF), a small amount of foreign-body giant cell (≤3/HPF), it is seen that cambium cannot be integral with diaphragm length, repair relatively slow, and have foreign material repulsion to react.

Continuing observation and cause 12 weeks after operation, period implants the miniature pig of I group of polypropylene net sheet material, has irritated performance, has friction in house interior walls and railing, tail biting performance, and the mental status is the best.Remaining tests miniature pig, movable normal, raises place in broadness and puts in a suitable place to breed.

12 weeks after operation, often group puts to death two animals, cuts include repairing the vagina including implant and bladder specimen at the bottom of basin.Touch with hands, during the most postoperative 4 weeks of I group of polypropylene net sheet material, still keep suitable hardness, and have obvious foreign body sensation；II group of fiber diaphragm is softer, but touches between implant site and surrounding tissue, still suffers from substantially distinguishing；The pliability of experimental group III-VII implantation film is the most close with autologous tissue, and does not substantially have obvious feel to distinguish between embedded material position and surrounding tissue；Wherein the sense of touch of V group of material is almost consistent with autologous tissue.

Perusal, III-VII group implantation film material and being organized into of growing are integrated, it is impossible to differentiate and peel off, and entirety presses close to tissue, and blood vessel is high-visible.Microscopic observation result shows, it is tightly combined with collagen fiber, fibrocyte around III-VII group implantation film, it is impossible to distinguish cambium and diaphragm material, internal visible substantial amounts of collagen fiber, visible cambium is completely integral with diaphragm length, it is achieved rebuilds and repairs；Pathological examination shows, all visible a large amount of fibroblasts in material surface and inside and collagen, has no that foreign-body giant cell and lymphocyte, material combine together with newborn tissue, it is difficult to distinguish.Visible higher loft is more beneficial for inducing cell and grows into and tissue regeneration, the pliability the being suitable for laminating to being more beneficial for implant site cambium and surrounding tissue, and it should be evident that cambium does not the most cause foreign body sensation, or newborn or autologous tissue are caused frictionally damage.

Perusal, II group of fiber diaphragm and cambium can peel off, more blood capillary seen from surface；Microscopic observation result shows, is combined with obvious boundary line with collagen fiber, fibrocyte around II group of fiber diaphragm, it is easy to distinguish cambium and diaphragm material, and surface has a large amount of collagen fiber, blood capillary abundant, inside still visible material；Pathological examination shows, material surface has more fibroblast and a large amount of angiogenesis (5-10/HPF), internal visible a small amount of blood capillary (≤3/HPF), 1/HPF of foreign-body giant cell, visible cambium is grown into inside diaphragm, but cambium is relatively fewer, and there is slight foreign body reaction.I group of polypropylene mesh, repairs position and produces level Four (using Nari adhesion point system 1) adhesion with surrounding tissue, and material is relatively easily peeled with the tissue grown, and polypropylene material is clearly visible, and material internal has no that cambium is grown into, penetrated；Pathological examination shows, only surrounding materials has a small amount of fibroblast and collagen to be formed, more blood capillary proliferation seen from surface (3-5/HPF), a large amount of foreign-body giant cells and lymphocytic infiltration, foreign body reaction and immunologic rejection are serious, visible cambium cannot be integral with diaphragm length, and repairing effect is poor.Speculate that the reason of observation process correspondence experiment pig agitation performance is probably foreign body sensation and tissue infection strong reaction simultaneously.

Embodiment 10

The fibrous layer (C) of the No yield point that the conventional electrospinning of employing obtains makes double layer fibre film (being called for short unordered fluffy film) with fluffy fiber layer (A3) film that embodiment 3 obtains by the method for embodiment 7 step (2).

With above-mentioned unordered fluffy film as a control group, the double layer fibre film (being called for short orderly fluffy film) of embodiment 7 is experimental group, carries out zoopery, to verify the effect of ordered structure.

Laboratory animal selects 12 healthy new zealand rabbits, body weight 2.0-2.5Kg, and male and female do not limit, rabbit about 6-12 in age month.Experimental rabbit is randomly divided into 3 groups, often group 4.Experimental group and matched group were all cut out as 1cm × 4cm strip, implant rabbit subcutaneous abdomen respectively, in postoperative 2 weeks, 3 months observation material surface tissue growth situations.

Method for implantation: by rabbit abdominal part for hair, sterilization, along midline incision skin of abdomen, blunt separation subcutaneous fascia and muscle, expose suitable material transplanting scope.Implanting the experimental group sample of 3 1cm × 4cm between subcutaneous and fascia on the left of interlayer, the control sample of 3 1cm × 4cm is implanted on right side.Material is fixed on corresponding position with No. 4 lines, sews up subcutaneous fascia layer and skin layer respectively.

After 2 weeks, fluffy of experimental group and matched group all has slim fibers encapsulation, and implant site blood capillary enriches.Observe after taking out portion of material dyeing, have the growth of obvious cell and orientation of creeping above the oriented layer in experimental group, and the growth of the omnidirectional confluent monolayer cells of matched group is at random.After three months, two groups of samples take out part observation, have obvious fibrous tissue to orient texture above experimental group oriented fiber layers, and the omnidirectional fibrous layer of matched group does not then have.Visible directional orientation fibrous layer (B) is more beneficial for guiding cell to creep and tissue compliance grows, and repair tissue is closer to natural fascia tissue.

Claims

1. use for treating the tissue repair of female pelvic floor dysfunctional disease for one kind Implantation film, it is characterised in that described implantation film includes fluffy fiber layer (A)；

Described fluffy fiber layer (A) is by the cellosilk intertexture of a diameter of 10nm～100 μm Becoming, have vesicular texture, its loft is 400～1500cm³/ g, its pliability is 50～500 milli-newton, wherein:

Loft=apparent thickness/surface density × 10³,

Wherein, loft is with cm³/ g represents, apparent thickness represents with mm, surface density With g/m²Represent；

Pliability refers to that the diaphragm tested out according to method in GB/T 8942-2002 resists At bending force and diaphragm and gap, the maximum vector sum of frictional force, represents with milli-newton.

Implantation film the most according to claim 1, wherein said fluffy fiber layer (A) average pore size is 50～500 μm.

Implantation film the most according to claim 1 and 2, wherein said fluffy fiber The thickness of layer (A) is 0.2～2mm, and tensile strength is 10～300N/cm.

Implantation film the most according to claim 1 and 2, wherein said fluffy fiber The loft of layer (A) is 800～1300cm³/g。

Implantation film the most according to claim 1 and 2, wherein said fluffy fiber The pliability of layer (A) is 200～450 milli-newton.

Implantation film the most according to claim 1 and 2, wherein said fluffy fiber Layer (A) uses the method including electrostatic spinning step to prepare.

Implantation film the most according to claim 1 and 2, wherein said implantation film Farther including oriented fiber layers (B), described oriented fiber layers (B) is fixed by cellosilk The layer with cellular three dimensional structure formed to arrangement.

Implantation film the most according to claim 7, wherein said oriented fiber layers (B) the filametntary a diameter of 10nm in～20 μm.

Implantation film the most according to claim 1 and 2, wherein said implantation film In combine by the way of electrostatic spinning, ultrasonic fusion or stitching between each layer.

Implantation film the most according to claim 1 and 2, wherein said implantation film Sheet comprises hemostasis class medicine, anti-infection drug, cell growth regulator, toxicity Inhibitor, anesthetis micro-nano granules and/or the medicine for the treatment of urinary incontinence.

11. according to the implantation film described in any one of claim 1 or 2, wherein said The surface of implantation film comprises hemostatic layer.

12. implantation films according to claim 11, wherein said hemostatic layer bag Containing collagen, polyoxyethylene fibre, chitosan, fibrin, peptide and/or blood coagulation Enzyme.

13. implantation films according to claim 11, wherein said hemostatic layer is led to The method crossing electrostatic spinning, lyophilization, forced air drying or vacuum drying is formed.

14. implantation films according to claim 1 and 2, wherein said implantation film The fibrous material of sheet is degradation material, non-degradable material or a combination thereof.

15. implantation films according to claim 14, wherein said degradable material Material selects free polylactic acid, polycaprolactone, polyglycolic acid, poly lactic-co-glycolic acid common Polymers, Lanthanum Isopropoxide, collagen protein, gelatin, fibrin, fibroin, In the group of the peptide polymer of elastin mimicry, chitosan and modification of chitosan composition One or more.

16. implantation films according to claim 14, wherein said non-degradable Material choosing freely poly-fluorine material, polyolefin, polyurethane, polyamide, polyester and silicone One or more in the group of rubber composition.

17. implantation films according to claim 1 and 2, wherein said implantation film Sheet has the through hole running through described implantation film upper and lower surface.

18. implantation films according to claim 17, wherein said through hole Aperture is 0.2-4mm.

The preparation side of 19. 1 kinds of implantation films as described in any one of claim 1-18 Method, it is characterised in that the preparation method of described implantation film includes preparing fluffy fiber The step of layer (A), the described step preparing fluffy fiber layer (A) includes:

(1) by two kinds of different for dissolution properties fibrous materials, it is dissolved in the most molten respectively In agent, obtain the fibrous material solution of both of which one；

(2) the both of which one fibrous material solution obtained in step (1) is filled respectively Enter in different electrostatic spinning syringes, through electrostatic spinning, obtain two kinds of dissolubilities The fibrous membrane of the mutual crisscross intersection of cellosilk that matter is different；

(3) according to the dissolution properties of cellosilk material, with solvent by step (2) A kind of cellosilk in the fibrous membrane manufactured dissolves, and another then keeps constant, To described fluffy fiber layer (A).

The preparation side of 20. 1 kinds of implantation films as described in any one of claim 1-18 Method, it is characterised in that the preparation method of described implantation film includes preparing fluffy fiber The step of layer (A), the described step preparing fluffy fiber layer (A) includes:

(2) the homogeneous fibrous material solution obtained in step (1) is loaded Static Spinning In silk syringe, carry out electrostatic spinning and obtain fiber, and fiber is received as membranaceous knot Structure, obtains fibrous membrane；

(3) by the fibrous membrane for preparing in step (2) after solvent supersonic is swelling State under, carry out pre-freeze, then carry out vacuum lyophilization, obtain described fluffy Fibrous layer (A).

21. preparation methoies according to claim 20, wherein said step (3) In, it is 50 volume %～95 bodies by the fibrous membrane concentration prepared in step (2) After the ethanol water infiltration of long-pending %, then carry out ultrasonic swelling in water.

The preparation side of 22. 1 kinds of implantation films as described in any one of claim 1-18 Method, it is characterised in that the preparation method of described implantation film includes preparing fluffy fiber The step of layer (A), the described step preparing fluffy fiber layer (A) includes:

(2) the homogeneous fibrous material solution obtained in step (1) is loaded Static Spinning In silk syringe, obtain fibrous membrane through electrostatic spinning；

(3) by the fibrous membrane of preparation in step (2) along the transverse axis of fibrous membrane or the longitudinal axis One of direction stretching, stop stretching after make fibrous membrane shape under this extended state； Then by fibrous membrane along the direction stretching vertical with above-mentioned draw direction of fibrous membrane, stop Only make fibrous membrane shape under this extended state after stretching, obtain described fluffy fiber Layer (A).

23. preparation methoies according to claim 22, wherein draw in step (3) The draft temperature stretching described fibrous membrane is less than materials hot deformation temperature 0 DEG C～the temperature of 30 DEG C Degree, rate of extension is 50～400mm/min, and tensile elongation is the 1.5～6.0 of original length Times, shaping time is 1h～4h.

24. according to the preparation method described in any one of claim 19-23, wherein, institute State preparation method and farther include to prepare with electrostatic spinning the step of oriented fiber layers (B).

25. 1 kinds for treating the implantable medical device of female pelvic floor dysfunctional disease Tool, it is characterised in that described implanted medical device comprises any one of claim 1-18 Described implantation film.

26. implanted medical devices according to claim 25, wherein said implantation Medical apparatus and instruments is no-station pole canopy urinary incontinence suspender or pelvic floor sticking patch.

27. implanted medical devices according to claim 26, wherein said nothing is opened Power urinary incontinence suspender includes main part and end, and described main part is wanted by right Asking the implantation film described in any one of 1-18 to make, described end is led for operating theater instruments Draw and/or for fixing.

28. implanted medical devices according to claim 27, wherein said main body Part has straight line or corrugated outline.

29. implanted medical devices according to claim 28, wherein said ripple The concavo-convex stand out of shape is 1mm-5mm.

30. implanted medical devices according to claim 26, wherein said pelvis End sticking patch includes the middle part bulk portion for repairing the prolapsus of pelvic cavity viscera, bulging, Described middle part bulk portion is by the implantation film system described in any one of claim 1-18 Become.

31. implanted medical devices according to claim 30, wherein said pelvis End sticking patch includes being positioned at bulk portion periphery, middle part for suspend prolapsus pelvic cavity viscera in midair Arm structure.