CN102580166A - Medical bionic transparent film implanting material, and preparation method and application of material - Google Patents
Medical bionic transparent film implanting material, and preparation method and application of material Download PDFInfo
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Abstract
The invention discloses a medical bionic transparent film implanting material which is a transparent porous material generated by electrostatic spinning and crosslinking. The thickness of the film ranges from 0.400 mu m to 800 mu m, the transparency of the film ranges from 75.0% to 99.9%, and the film comprises the following components in percentage by weight: 75.00%-95.00% of collagen, 1.50%-15.00% of polysaccharides, 0.01%-3.00% of therapeutic substances, and the balance being water. The film is prepared by an electrostatic spinning method. According to the invention, the technology is simple, the whole process is free of pollution, the transparency of the film is high, and the implanting material has a function of slow releasing on the loaded therapeutic substances, can remarkably improve a human tissue damage repair effect, and can be applied to ocular surface damage membrana tectoria, skin wound dressing, bone tooth defect regeneration guide films and other viscera repair separation films.
Description
Technical field
The present invention relates to a kind of medical bionical transparent membrane embedded material, the method for preparing of especially in-situ therapeutic substance-loaded collagen base bionic transparent thin-film material and application belong to biological medicine, technical field of biological materials.
Background technology
People's eye table, skin etc. are organized and are caused tissue injury because of bacterial infection, disease, corrosive substance or wound easily, and the wound surface that adopts thin film class medical embedded material to cover to expose can abirritate or the purpose of the reparation that maybe and reach promotion tissue injury infected of pain symptom, reduction.Similarly, in the bones such as skull of periosteum well damage are damaged, cover again behind filler particles, block or the self-curing biomaterial artificial guiding film that one deck has natural periosteum function can guide damaged in osteanagenesis, can avoid the meat fiber tissue to grow into again.In addition; Adhesion is that connective fiber band and adjacent tissue or organ combine and the anomalous structure that forms; After the plastic surgery operations, the formation of adhesion and scar tissue is prone to cause the complication of severe postoperative, like adhesion of tendon, peripheral nerve adhesion, eye socket damage back soft tissue adhesion etc.; Usually hinder rehabilitation, thereby employing bio-medical thin-film material is a kind of tissue adhesion's of avoiding effective way as spacer.For a long time The experimental results and clinical practice show that ideal medical film class embedded material need possess the integrated of many functions, like good biocompatibility, in order to avoid cause new pathological changes; Promote the biological activity of tissue regeneration, the quick expression of ability active adjustment relevant cell propagation, differentiation and the required factor of tissue regeneration; Suppress bacteria breed, avoid infection; Superior degradability, so that material is continued to absorb or metabolism in the regeneration and restoration process, the realization function is rebuild fully.In addition, the good transparency helps observing wound repair process situation, and can reduce the secondary damage of changing dressings and causing; The thin-film material of in eye table injury repairing, implanting does not influence eye table vision.Therefore, the multi-functional bionic thin film material of highly transparent has great clinical value and demand.
At present, the exploitation of transparent thin-film material obtains fast development, and synthetic macromolecular material, natural macromolecular material and composite are all by broad research.One pack system thin-film material by preparations such as synthetic polymer substance such as terylene, polyethylene, polrvinyl chloride, politef, polylactic acid, polycaprolactone, polyvinyl alcohol; Though have higher tensile strength; But give especially biological activity of biocidal property, biocompatibility with being difficult to collaborative coupling, thereby promote the biological effect of damage Regeneration and Repair and the convenience of application to be difficult to coordinate.The thin film that the traditional sialorrhea evaporations of employing such as natural high molecular substance such as collagen, gelatin, chitosan, mucopolysaccharide, hyaluronic acid or its mixture are processed, though have the good transparency and biocompatibility, mechanical strength and plasticity are relatively poor.Hou Jiang equal utilization collagen and chitosan mixed solution have prepared transparent composite membrane through simple casting film-forming, and in the corneal injury reparation, shown certain effect (Hou Jiang equality, China organizes the worker to study and clinical rehabilitation. and 2010; 14:6319-6322).In addition; Though puerpera's amniotic membrane, pig small intestine Submucosa, xenogenesis pericardium, animal corium etc. have the excellent mechanical property and the transparency from the natural thin film of various tissues, organ; And contain a large amount of cytokines and anti-inflammatory component can promote wound repair; But also have allosome pathophoresis, allosome immunologic rejection problem, biological safety is difficult to guarantee to be the material risk of clinical practice.From technology of preparing; Adopt that biological coating technology, chemical crosslinking are technological, conventional molds mold technology increased biocompatibility with the compounded thin film of synthetic macromolecular material with natural biological macromolecule such as collagen, gelatin, chitosan, hyaluronic acid etc. when guaranteeing mechanical strength; But combined efficiency is restive; Especially these thin film have only possessed form bionical; Its micro-nano structure does not possess the basic feature of organism inner cell epimatrix, thereby the not enough significantly promotion of biological effect injury repairing, thereby influences clinical treatment efficient and effect.
Aspect bio-medical transparent membrane product; It is peripheral that the Tegaderm transparent membrane product of 3M company exploitation has made up the window frame formula; Be convenient to paste, but this product only has the function that isolate bacteria infects with the damage periphery, only ventilative and do not possess water penetration; Easily influence the unobstructed property that the skin class is organized perspire, and then jeopardize wound repair.Domestic in recent years various big hospital is a large amount of during intravenous injection clinically to use transparent membranes control antibacterials in the acupuncture position gets into body, and these transparent membranes only are the wound surface buffer actions, do not bring into play the mastery reaction of treatment.Also have one type of plaster can be attached on the skin, be mainly used in pain relieving and the little wound of treatment.Disclose a kind of transparent plaster among the Chinese invention patent CN 201631488U and only supplied with medicine, but self do not possessed bionical and metabolic characteristics.Singapore's biological engineering and nanotechnology research a kind of thermal sensitivity of staff development gather (N-Isopropylacrylamide) [poly (N-isopropylacrylamide); Be called for short PNIPAAm] transparent nano hole thin film; Demonstrate good temperature dependency dilatancy; But do not possess bionical micro structure and biological activity etc., thereby be merely providing convenience property of observation wound healing (Wang L-S, et al.
Adv Mater.2004; 16:1790-1794).Simultaneously; They have also reported a kind of by chitosan and the compound transparent thin-film material of alginate; Although the thin film that utilization calcium chloride is the gel cast to form is transparent; But on micro-nano structure, be formed by stacking, also there are differences (Wang L-S, et al. with the nanofiber ultrastructure of extracellular matrix sheet polymer
J Biomed Mater Res Part B:Appl Biomater. 2002; 63:610-618).United States Patent (USP) 4505855 discloses a kind of transparent collagen film of supercentrifugation preparation; There is not the nanofiber form of extracellular matrix in this thin-film material on micro-nano structure; And single collagen film material mechanical performance is poor; Biological effect only depends on this native protein of collagen, is difficult to be implemented in the damage of antibacterial, infection and Synergistic treatment, and its therapeutic efficiency is still undesirable.
In recent years, electrostatic spinning technique is owing to making a kind of new way that becomes the preparation thin film with the extremely similar non-woven fabrics product of n cell epimatrix nanofibrous structures.It is to make the nano level superfine fiber that polymer solution or melt generation jet-action form through strong electrostatic field.This technology equipment needed thereby is simple, controls easy enforcement, can be through adjustment process parameter control fibre diameter and orientation.Bergshoef etc. take the lead in having reported that a kind of electrical spinning method prepares nylon-4,6 transparent thin-film material, although the micro structure from nanoscale has been given certain bionical characteristic (Bergshoef MM, et al.
Adv Mater.1999; 11:1362-1365), but its material biological activity, degradability are poor, and bio-medical must receive the influence of these problems.Recently; The India scholar utilizes the polycarbonate film of electrostatic spinning technique system to attempt to use eye table injury repairing, and this thin film has the endothelial cell proliferation of promotion characteristic, but its transparency is relatively poor; Thereby restricted at application prospect (Sharma S, the et al. of clinical this kind thin film in the damage of eye table
Molecular Vision2011; 17:2898-2910).Chinese invention patent CN1456716 discloses a kind of technology of utilizing natural or synthesized polymer material to carry out electrostatic spinning; Chinese invention patent CN 1584143A discloses a kind of nanometer fiber slow-releasing system that utilizes the preparation of electric spining technology to be loaded with somatomedin; A kind of nanometer fiber slow-releasing thin film that utilizes the method for electrostatic spinning preparation to be loaded with anti-inflammatory medicaments and somatomedin is disclosed among the Chinese invention patent CN 1739491A.In addition, the research that utilizes this technology to carry out natural biological molecular bionics nano-fiber film material also becomes focus gradually.Much in skin injury reparation etc., carried out big quantity research so far, but these researchs the transparency of giving material or load therapeutic substance have often been ignored to strengthen the treatment function about compound nano-fiber film materials such as collagen and chitosan, hyaluronic acids.This shows that electrostatic spinning technique has very big potentiality aspect the multi-functional high transparent membrane of preparation.
Therefore; According to prior art and research report; Need to explore can be easy with fast filming, can give the multiple function that promotes the quick Regeneration and Repair of damage and the bionic-type medical film embedded material of highly transparent, satisfy clinically eye table injury repairing, promote soft tissue injury to repair, prevent huge applications demands such as glutinous sticking, guiding osteanagenesis fast with this.
Summary of the invention
The purpose of this invention is to provide the medical bionical transparent membrane embedded material that a kind of technology is easy, can give various biological effect and function.
Medical bionical transparent membrane embedded material of the present invention is that film thickness is 0.400 ~ 800 micron through electrostatic spinning and the crosslinked transparent porous membrane that obtains, and the transparency of thin film is 75.0 ~ 99.9%, and the mass percent content of each component is in the thin film:
Collagen 75.00 ~ 95.00%;
Polysaccharide 1.50 ~ 15.00%;
Therapeutic substance
0.01 ~ 3.00%;
All the other are water, and the said components sum is 100%.
The method for preparing of medical bionical transparent membrane embedded material of the present invention, step is following:
1) with collagenolysis in mass concentration is 2 ~ 100% acetic acid aqueous solution, be mixed with the collagen solution that concentration is 10 ~ 100 mg/ml;
2) in above-mentioned collagen solution, add polysaccharide material by 0.5 ~ 5.0 mg/ml, after the stirring and dissolving, add therapeutic substance and stirring and dissolving again, the concentration of therapeutic substance is 0.01 ~ 0.40 mg/ml;
3) with step 2) mixed solution pack in the propulsion system reservoir of electrostatic spinning apparatus; With the conductor plate is received vector; Regulating the hollow metal shower nozzle of propulsion system front end and the spacing of received vector is 5 ~ 25 centimetres, and carrier is used lead ground connection, and the hollow metal shower nozzle connects 5 ~ 25 Kilovolt Direct Currents and presses; Mixed solution in the propulsion system is released with 0.1 ~ 2.0 milliliter/hour speed; Carry out electrostatic spinning after 0.2 ~ 10 hour, nanofiber is independently piled up on received vector, forms the porous membrane with hole;
4) take porous membrane off from carrier; Crosslinked 1 ~ 10 hour of porous membrane is crosslinked with ultraviolet radiation, photochemical crosslinking or chemical cross-linking agent; Using pH then is 7.0 phosphate buffer rinsing repeatedly, again through dried, obtains therapeutic substance-loaded medical bionical transparent membrane embedded material.
Among the present invention, said collagen is I, II or IV Collagen Type VI.
Among the present invention, said polysaccharide is one or more the combination in any in chitosan, hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin, alginic acid, Heparan sulfate and their the soluble salt material.
Among the present invention, said therapeutic substance is antibacterial, analgesic agent, immunosuppressant, steroid hormone or promotes the factor that tissue injury repairs, and under no incompatibility situation the mixture of two or more material.
The factor that above-mentioned promotion tissue injury repairs is recombinant human horny cell growth factor-2, insulin like growth factor, human hepatocyte growth factor, fibroblast growth factor, transforming growth factor, epidermal growth factor or VEGF; Above-mentioned antibacterial is ampicillin, cefradine, cilastatin, azithromycin, metrizamide star, nanometer-level silver granule or bioactivity glass nanoparticle.Analgesic agent is aspirin, acetaminophen, indomethacin, ibuprofen, nimesulide or celecoxib.
Among the present invention, said chemical cross-linking agent is glutaraldehyde, genipin, acetic anhydride, diglycidyl ether, hot two imidic acid methyl ester, carbodiimide, N monohydroxy butanimide or 2--morpholino ethane sulfonic acid.
The purposes of medical bionical transparent membrane embedded material of the present invention is to be used for treating the damage of human body eye table, skin injury, the anti-glutinous application that connects isolation, the damaged regeneration guiding film of bone tooth of visceral organ injury.
The present invention prepares in the process; Through the distance between the concentration, spout and the received vector that change collagen, polysaccharide in voltage and the solution, the fltting speed and the spinning film formation time of solution; Can control the diameter of fiber and the thickness of thin film; Usually, the fibre diameter of formation porous membrane is 40 ~ 1000 nanometers on the received vector.
Beneficial effect of the present invention is:
Medical transparent bionic thin film embedded material of the present invention is to adopt method of electrostatic spinning to make the nanofiber biomimetic features that is similar to the n cell epimatrix collagen, polysaccharide, for the growth of damage location cell and tissue reconstruction provide highly bionical microenvironment.For example collagen is the main component of human tissue cell's epimatrix, helps the cell adhesion growth, promotes the function of wound healing; Hyaluronic acid is the knuckle synovia important component, can promote eye table, skin injury reparation; Chitosan is the macromolecule alkalescence polysaccharide of natural origin, and is nonpoisonous and tasteless, and human body is had no side effect, have exudation, anti, hemostasis, can be by functions such as human body absorptions.Therefore in the compound system of collagen-polysaccharide, introduce other therapeutic substance and have good promotion cell growth effect through electrostatic spinning formation thin-film material; Electrostatic spinning prepares process therapeutic substance is had the embedding effect, thereby reaches the function of sustained release.Secondly, electrostatic spinning film has heigh clarity, stronger mechanical strength and plasticity through crosslinking Treatment, and comprehensive mechanical property reaches the mechanical property of puerpera's amniotic membrane.Once more; Naturally it is big to pile up the thin film specific surface area that forms by nano-scale fiber, has the porous permeability performance, can adsorb a large amount of moisture; Have preserving moisture and lubricate, promote cell growth, adjusting cell migration and dehumidifying effect; The wound healing regeneration capacity be can improve, and cicatrix, enhancing immunity reduced.Distinguishing features such as technological process of the present invention is simple, and it is controlled that the comprehensive organism effect of thin film is adjustable.
The present invention adopts electrostatic spinning technique and cross-linking method; Polysaccharide macro-molecular and collagen, curative drug are carried out compound, the gained collagen base film transparency is good, has the nanostructured that is similar to the n cell epimatrix; Can promote the regeneration of tissue; The slow degraded of thin film simultaneously realized therapeutic substance-loaded sustained release, can well alleviate the wound inflammatory reaction, and the collaborative tissue repair that promotes.
Medical bionical transparent membrane embedded material of the present invention has the integrated of good biocompatibility and various biological effect, in eye table, skin, internal organs, the damage of bone tooth, has a good application prospect.
Description of drawings
Fig. 1 is that the present invention prepares the type i collagen-chitosan nano fiber transparent membrane electromicroscopic photograph (scale is represented 1 μ m) that contains epidermal growth factor.
Fig. 2 is that the present invention prepares I collagen-chitin nanofiber transparent membrane and the puerpera's amniotic membrane stretching mechanical test stress-strain comparison diagram that contains epidermal growth factor; Curve 1 is puerpera's amniotic membrane among the figure, and curve 2 is nanofiber transparent membranes that epidermal growth factor is carried in electrostatic spinning and chemical crosslinking.
Fig. 3 is II Collagen Type VI-chitosan-hyaluronic acid nano fiber transparent membrane electromicroscopic photograph (scale is represented 1 μ m) that the present invention prepares the sulfur acid chrondroitin.
Fig. 4 is II Collagen Type VI-chitosan-hyaluronic acid nano fiber transparent membrane and the puerpera's amniotic membrane stretching mechanical test stress-strain comparison diagram that the present invention prepares the sulfur acid chrondroitin, and curve 1 is puerpera's amniotic membrane among the figure, and curve 2 is transparent membranes of sulfur acid chrondroitin.
Fig. 5 is that the present invention prepares the type i collagen-chitosan nano fiber transparent membrane electromicroscopic photograph (scale is represented 1 μ m) that contains nano-Ag particles.
The specific embodiment
Embodiment 1
1) type i collagen being dissolved in mass concentration is that being mixed with concentration is the type i collagen solution of 85 mg/ml in 80% the acetic acid aqueous solution;
2) in above-mentioned type i collagen solution, add the chitosan material by 4.0 mg/ml, after the stirring and dissolving, add epidermal growth factor and stirring and dissolving again, the concentration of epidermal growth factor is 0.40 mg/ml;
3) with step 2) mixed solution that stirs packs in the propulsion system reservoir of electrostatic spinning apparatus; With the conductor plate is received vector; Regulating the hollow metal shower nozzle of propulsion system front end and the spacing of received vector is 12 centimetres, and carrier is used lead ground connection, and the hollow metal shower nozzle connects 15 Kilovolt Direct Currents and presses; Mixed solution in the propulsion system is released with 0.3 milliliter/hour speed; Carry out electrostatic spinning after 6 hours, nanofiber is independently piled up on received vector, forms the porous membrane with hole;
4) take porous membrane off from carrier, with 0.2% glutaraldehyde solution chemical crosslinking 4 hours, using pH then was 7.0 phosphate buffer rinsing repeatedly, again through dried, obtains containing the transparent thin-film material of epidermal growth factor with porous membrane.
The transparency of this thin film is 93.4%; Thickness is 300 microns; Contain type i collagen, chitosan and epidermal growth factor and be respectively 93.5%, 4.4% and 0.44%, the fibre structure pattern of this transparent membrane of electron microscopic observation is shown in accompanying drawing 1, and the mechanics extension test is shown in accompanying drawing 2; Show that success prepares the bionical transparent membrane of collagen-chitin composite nano fiber that carries epidermal growth factor, this bionic thin film has mechanical performance preferably.
Embodiment 2
1) the II Collagen Type VI being dissolved in mass concentration is that being mixed with concentration is the II Collagen Type VI solution of 70 mg/ml in 65% the acetic acid aqueous solution;
2) in above-mentioned II Collagen Type VI solution, add equivalent chitosan, hyaluronic acid material by total concentration 3.0 mg/ml, after the stirring and dissolving, add chondroitin sulfate and stirring and dissolving again, the concentration of chondroitin sulfate is 0.20 mg/ml;
3) with step 2) mixed solution that stirs packs in the propulsion system reservoir of electrostatic spinning apparatus; With the conductor plate is received vector; Regulating the hollow metal shower nozzle of propulsion system front end and the spacing of received vector is 10 centimetres, and carrier is used lead ground connection, and the hollow metal shower nozzle connects 10 Kilovolt Direct Currents and presses; Mixed solution in the propulsion system is released with 0.2 milliliter/hour speed; Carry out electrostatic spinning after 8 hours, nanofiber is independently piled up on received vector, forms the porous membrane with hole;
4) take porous membrane off from carrier, with porous membrane with irradiation under ultraviolet ray crosslinked 6 hours, using pH then was 7.0 phosphate buffer rinsing repeatedly, again through dried, obtains the transparent thin-film material of sulfur acid chrondroitin.
The transparency of this thin film is 88.9%; Thickness is 560 microns; Contain II Collagen Type VI, chitosan, hyaluronic acid and chondroitin sulfate and be respectively 91%, 1.95%, 1.95% and 0.26%, the fibre structure pattern of this transparent membrane of electron microscopic observation is shown in accompanying drawing 3, and the mechanics extension test is shown in accompanying drawing 4; Show that success prepares the collagen-chitin of sulfur acid chrondroitin-bionical transparent membrane of hyaluronic acid composite nano fiber, this bionic thin film has mechanical performance preferably.
Embodiment 3
Method for preparing is with embodiment 1; Difference is: change 0.40 mg/ml epidermal growth factor into 0.10 mg/ml nano-Ag particles, change the DC voltage that metal needle applied into 8 kV, regulate the hollow metal shower nozzle of propeller front end and the spacing of fiber received vector and change 10 centimetres into; Mixed solution in the propeller is released with 0.25 milliliter/hour speed; Carried out electrostatic spinning 7 hours, the particulate superfine fibre of carrying nano silver is independently piled up on received vector, forms the porous film with certain hole and thickness; With porous membrane with 0.15% glutaraldehyde solution chemical crosslinking 4 hours; Using pH then is 7.0 phosphate buffer rinsing repeatedly, again through dried, obtains containing the transparent thin-film material of nanometer silver.The transparency of this thin film is 83.6%; Thickness is 680 microns; Contain type i collagen, chitosan and nanometer silver and be respectively 93.5%, 4.4% and 0.11%; The fibre structure pattern of this transparent membrane of electron microscopic observation shows that success prepares the bionical transparent membrane of collagen-chitin composite nano fiber that contains the nanometer silver granuel shown in accompanying drawing 5.
Claims (10)
1. medical bionical transparent membrane embedded material; It is characterized in that it is through electrostatic spinning and the crosslinked transparent porous membrane that obtains; Film thickness is 0.400 ~ 800 micron, and the transparency of thin film is 75.0 ~ 99.9%, and the mass percent content of each component is in the thin film:
Collagen 75.00 ~ 95.00%;
Polysaccharide 1.50 ~ 15.00%;
Therapeutic substance
0.01 ~ 3.00%;
All the other are water, and the said components sum is 100%.
2. the method for preparing the described medical bionical transparent membrane embedded material of claim 1 is characterized in that step is following:
1) with collagenolysis in mass concentration is 2 ~ 100% acetic acid aqueous solution, be mixed with the collagen solution that concentration is 10 ~ 100 mg/ml;
2) in above-mentioned collagen solution, add polysaccharide material by 0.5 ~ 5.0 mg/ml, after the stirring and dissolving, add therapeutic substance and stirring and dissolving again, the concentration of therapeutic substance is 0.01 ~ 0.40 mg/ml;
3) with step 2) mixed solution pack in the propulsion system reservoir of electrostatic spinning apparatus; With the conductor plate is received vector; Regulating the hollow metal shower nozzle of propulsion system front end and the spacing of received vector is 5 ~ 25 centimetres, and carrier is used lead ground connection, and the hollow metal shower nozzle connects 5 ~ 25 Kilovolt Direct Currents and presses; Mixed solution in the propulsion system is released with 0.1 ~ 2.0 milliliter/hour speed; Carry out electrostatic spinning after 0.2 ~ 10 hour, nanofiber is independently piled up on received vector, forms the porous membrane with hole;
4) take porous membrane off from carrier; Crosslinked 1 ~ 10 hour of porous membrane is crosslinked with ultraviolet radiation, photochemical crosslinking or chemical cross-linking agent; Using pH then is 7.0 phosphate buffer rinsing repeatedly, again through dried, obtains therapeutic substance-loaded medical bionical transparent membrane embedded material.
3. the method for preparing of medical bionical transparent membrane embedded material according to claim 2 is characterized in that said collagen is I, II or IV Collagen Type VI.
4. the method for preparing of medical bionical transparent membrane embedded material according to claim 2 is characterized in that said polysaccharide is one or more the combination in any in chitosan, hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin, alginic acid, Heparan sulfate and their the soluble salt material.
5. the method for preparing of medical bionical transparent membrane embedded material according to claim 2; It is characterized in that said therapeutic substance is antibacterial, analgesic agent, immunosuppressant, steroid hormone or promotes the factor that tissue injury repairs, and under no incompatibility situation the mixture of two or more material.
6. the method for preparing of medical bionical transparent membrane embedded material according to claim 5 is characterized in that the said factor that promotes tissue injury to repair is recombinant human horny cell growth factor-2, insulin like growth factor, human hepatocyte growth factor, fibroblast growth factor, transforming growth factor, epidermal growth factor or VEGF.
7. the method for preparing of medical bionical transparent membrane embedded material according to claim 5 is characterized in that said antibacterial is ampicillin, cefradine, cilastatin, azithromycin, metrizamide star, nanometer-level silver granule or bioactivity glass nanoparticle.
8. the method for preparing of medical bionical transparent membrane embedded material according to claim 5 is characterized in that said analgesic agent is aspirin, acetaminophen, indomethacin, ibuprofen, nimesulide or celecoxib.
9. the method for preparing of medical bionical transparent membrane embedded material according to claim 2 is characterized in that said chemical cross-linking agent is glutaraldehyde, genipin, acetic anhydride, diglycidyl ether, hot two imidic acid methyl ester, carbodiimide, N monohydroxy butanimide or 2--morpholino ethane sulfonic acid.
10. the application of the described medical bionical transparent membrane embedded material of claim 1 is characterized in that being used for treating the damage of human body eye table, skin injury, the anti-glutinous application that connects isolation, the damaged regeneration guiding film of bone tooth of visceral organ injury.
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