CN107376009A - A kind of biological response of synthetic materials used for keratoprosthesis and preparation method - Google Patents

A kind of biological response of synthetic materials used for keratoprosthesis and preparation method Download PDF

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Publication number
CN107376009A
CN107376009A CN201710774075.9A CN201710774075A CN107376009A CN 107376009 A CN107376009 A CN 107376009A CN 201710774075 A CN201710774075 A CN 201710774075A CN 107376009 A CN107376009 A CN 107376009A
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polyvinyl alcohol
carboxymethyl chitosan
keratoprosthesis
fibroin albumen
materials used
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周莉
王泽巩
罗仲宽
胡惠媛
林燕明
周金生
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Shenzhen University
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Shenzhen University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/16Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52Hydrogels or hydrocolloids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • A61L2300/232Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/16Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
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  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

The embodiment of the present invention provides a kind of biological response of synthetic materials used for keratoprosthesis and preparation method, is related to prosthetic material technical field.The material is composite aquogel, and composite aquogel is loose structure, including:Carboxymethyl chitosan, fibroin albumen and polyvinyl alcohol, wherein, the mass ratio of carboxymethyl chitosan, fibroin albumen and polyvinyl alcohol is 0.5~5:2~10:1~4, the molecular weight of polyvinyl alcohol is 1500~2000.Due to the excellent antibiotic property of carboxymethyl chitosan, fibroin albumen has good mechanical property, the compatibility with tissue, and polyvinyl alcohol has good water solubility, the material obtained by above-mentioned three kinds of materials can grow into for the composite aquogel of porous type in order to fibroblast and capillary, wound with porous type network, prevent the malposition that comes off of artificial cornea, and the inflammation of human cornea.

Description

A kind of biological response of synthetic materials used for keratoprosthesis and preparation method
Technical field
The invention belongs to prosthetic material technical field, more particularly to a kind of biological response of synthetic materials used for keratoprosthesis and preparation method.
Background technology
Keratonosus illness rate is high, it is blinding it is strong, treatment is difficult, be the blinding illness in eye being number two in the world.According to statistics Because the patient of keratonosus blinding there are about 50,000,000, China there are about 4,000,000 in the whole world, wherein 80% patient can be moved by cornea Plant operation to cast off illiteracy, however, on the one hand because donor's cornea source is deficient, most of cornea patient can not receive donor's cornea shifting Plant;Another aspect corneal transplantation is postoperative, which to produce various adverse reactions, causes cornea receptor treatment success rate very low.At present, make Manually cornea is treated to replace donor's cornea to patient.Artificial cornea is to use a kind of dioptric made of alloplastic material Device, by performing the operation, eye is suffered from implantation, substitutes muddy cornea tissue, to obtain eyesight.Artificial cornea has become vast corneal blindness The last hope of the reconstruction light of patient.
Current most widely used artificial cornea structure is " skirt-core " type, i.e., by porous skirt hanger material and optics Heart two parts form.Wherein, skirt hanger is the part directly contacted with plant bed, plays the work with human ocular tissues' cell fusion With, still, due to there is no good compatibility between the support in artificial cornea and tissue, cause artificial cornea be implanted into Afterwards, usually occur cornea come off, malposition, the complication such as inflammation.
The content of the invention
The present invention provides a kind of biological response of synthetic materials used for keratoprosthesis and preparation method, it is intended to solves existing artificial cornea and is being implanted into Afterwards, occur cornea come off, malposition, inflammation etc. complication the problem of.
A kind of biological response of synthetic materials used for keratoprosthesis provided by the invention, the material are composite aquogel, the composite aquogel For loose structure, including:Carboxymethyl chitosan, fibroin albumen and polyvinyl alcohol, wherein, the carboxymethyl chitosan, the silk The mass ratio of fibroin and the polyvinyl alcohol is 0.5~5:2~10:1~4, the molecular weight of the polyvinyl alcohol for 1500~ 2000。
A kind of preparation method of biological response of synthetic materials used for keratoprosthesis provided by the invention, methods described include:
Carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent and organic solvent are mixed, and at 80~100 DEG C Constant temperature adds crosslinking agent after stirring 2~4 hours under water-bath, by the pH regulations of mixture to 7~9;It is small to continue stirring 0.5~1.5 When;
The mixture that pH value is 7~9 is injected into the shaping of bracket mould pressing mold, and by the material of shaping at -20~-40 DEG C Freezing 10~48 hours, and thaw at room temperature, obtain the biological response of synthetic materials used for keratoprosthesis of porous composite aquogel;
Wherein, the molecular weight of the polyvinyl alcohol is 1500~2000, and the perforating agent is sodium chloride, the organic solvent For thionyl chloride, the crosslinking agent is Geniposide, the carboxymethyl chitosan, the fibroin albumen, the polyvinyl alcohol, described The mass ratio of sodium chloride, the thionyl chloride and the Geniposide is 0.5~5:2~10:1~4:5~15:5~20:0.1~ 0.25。
A kind of biological response of synthetic materials used for keratoprosthesis provided by the invention and preparation method, excellent due to carboxymethyl chitosan resist Bacterium property can avoid the part inflammation that artificial cornea support contacts.Using fibroin albumen on the one hand due to fibroin albumen and human body group Knitting good compatibility can support human fibroblast and keratocyte to grow, so that artificial cornea support pastes with human cornea Close close, avoid dystopy and come off, on the other hand due to the good mechanical property of fibroin albumen be also prevented from artificial cornea by In itself breaking releasing and malposition.Further, since polyvinyl alcohol has good water solubility, obtained material is porous type It composite aquogel, can grow into order to fibroblast and capillary, be wound with porous type network, it is artificial further to prevent Cornea comes off.
Brief description of the drawings
In order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing There is the required accompanying drawing used in technology description to be briefly described, it should be apparent that, drawings in the following description are only this Some embodiments of invention.
Fig. 1 is the scanning electron microscopic picture of biological response of synthetic materials used for keratoprosthesis provided by the invention.
Embodiment
To enable goal of the invention, feature, the advantage of the present invention more obvious and understandable, below in conjunction with the present invention Accompanying drawing in embodiment, the technical scheme in the embodiment of the present invention is clearly and completely described, it is clear that described reality It is only part of the embodiment of the present invention to apply example, and not all embodiments.Based on the embodiment in the present invention, people in the art The every other embodiment that member is obtained under the premise of creative work is not made, belongs to the scope of protection of the invention.
The invention provides a kind of biological response of synthetic materials used for keratoprosthesis, the material is composite aquogel, and the composite aquogel is more Pore structure, including:Carboxymethyl chitosan, fibroin albumen and polyvinyl alcohol, wherein, carboxymethyl chitosan, the fibroin albumen and poly- The mass ratio of vinyl alcohol is 0.5~5:2~10:1~4, the molecular weight of polyvinyl alcohol is 1500~2000.
In biological response of synthetic materials used for keratoprosthesis provided by the invention, because the excellent antibiotic property of carboxymethyl chitosan can avoid The part inflammation of artificial cornea support contact.Using fibroin albumen on the one hand due to fibroin albumen and tissue well compatible Property can support that human fibroblast and keratocyte grow, so that artificial cornea support is bonded closely with human cornea, are not easy Come off, on the other hand because the good mechanical property of fibroin albumen is also prevented from artificial cornea due to itself breaking releasing.Separately Outside, because polyvinyl alcohol has good water solubility, obtained material is the scanning electron microscope (SEM) photograph of porous type composite aquogel, can be with It is easy to fibroblast and capillary to grow into, is wound with porous type network, further to prevent coming off for artificial cornea.Such as figure Shown in 1, Fig. 1 is the porous type composite aquogel being prepared by the above method, and the material includes macropore and aperture, macropore diameter Size is 200~500 μm, and small aperture size is 1~10 μm.Composite aquogel made from the above method passes through three kinds of material systems It is standby to form, the shortcomings that overcoming homogenous material, make biological response of synthetic materials used for keratoprosthesis both had good biocidal property, biocompatibility, With the controllable property of excellent mechanical performance and degradation rate.
Specifically, carboxymethyl chitosan is O-CMC, N- carboxymethyl chitosans or CMC At least one of.Fibroin albumen is nanoscale silk fibroin powder or silk fibroin water solution.Preferably, carboxymethyl chitosan, The mass ratio of the fibroin albumen and polyvinyl alcohol is 2~4:5~7:2~3.
The invention provides a kind of preparation method of biological response of synthetic materials used for keratoprosthesis, this method includes:
Carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent and organic solvent are mixed, and at 80~100 DEG C Constant temperature adds crosslinking agent after stirring 2~4 hours under water-bath, by the pH regulations of mixture to 7~9;By the mixing that pH value is 7~9 Thing injection bracket mould pressing mold shaping, and the material of shaping is freezed 10~48 hours at -20~-40 DEG C, and in room temperature Lower defrosting, obtains the biological response of synthetic materials used for keratoprosthesis of porous composite aquogel;
Wherein, the molecular weight of polyvinyl alcohol is 1500~2000, and perforating agent is sodium chloride, and organic solvent is thionyl chloride, Crosslinking agent is Geniposide, carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, sodium chloride, the mass ratio of thionyl chloride and Geniposide For 0.5~5:2~10:1~4:5~15:5~20:0.1~0.25.
The preparation method of biological response of synthetic materials used for keratoprosthesis provided by the invention, due to the excellent antibacterial of carboxymethyl chitosan Property, moisture retention and adsorptivity, fibroin albumen has good mechanical property, the compatibility with tissue, and supports human body Fibrocyte and keratocyte growth, and polyvinyl alcohol have good water solubility, and above-mentioned substance is carried out using crosslinking agent Chemical crosslinking, it is physical crosslinking using freeze-thaw shaping, and three-dimensional porous composite aquogel is obtained using perforating agent.System The standby obtained i.e. porous carboxymethyl chitosan of biological response of synthetic materials used for keratoprosthesis, fibroin albumen, polyvinyl alcohol composite hydrogel, has drop Controllable-rate, high-moisture percentage, good mechanical property and certain antibiotic property are solved, may participate in the good biology such as tissue repair Compatibility, it may advantageously facilitate the surgical wound surface quickly effect such as healing and support fibroblast and keratocyte growth.Utilizing It is thin that human desmocyte is cultivated made from the preparation method of biological response of synthetic materials used for keratoprosthesis provided by the invention on biological response of synthetic materials used for keratoprosthesis Born of the same parents, by confocal laser scanning microscope, on biological response of synthetic materials used for keratoprosthesis, human fibroblasts propagation is rapid and arrangement is tight It is close, there is good biocompatibility.Can be very good to solve the problems, such as artificial cornea come off, malposition.In addition, this method Process is simple, is easy to industrialized production.
Alternatively, this method also includes:The material of shaping is freezed and thawed at room temperature each at -20~-40 DEG C Three times, biological response of synthetic materials used for keratoprosthesis is obtained.
Wherein, cooling time is 10~48 hours, and thawing time is 2~6 hours.
Alternatively, this method also includes:Biological response of synthetic materials used for keratoprosthesis is placed in aseptic deionized water and soaked 5~30 days.
Specifically, perforating agent can also be polyethylene glycol or polyvinylpyrrolidone.Crosslinking agent can also be glutaraldehyde.Hand over Connection agent helps to adjust crosslinking degree and speed of the crosslinking agent to composite aquogel, by controlling the dosage of crosslinking agent to control The degradation rate of composite aquogel and the pore size of loose structure.Carboxymethyl chitosan is O-CMC, N- carboxylics Methyl chitosan or at least one of N, O-CMC.Fibroin albumen is nanoscale silk fibroin powder or fibroin albumen The aqueous solution.
Preferably, it is carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent sodium chloride and organic solvent dichloro is sub- Sulfone mixes, and constant temperature adds crosslinking agent after stirring 3~4 hours under 85~95 DEG C of water-bath, by the pH of mixture regulation to 8~ 8.5;Continue stirring 1~1.5 hour.Wherein, the mass ratio of carboxymethyl chitosan, fibroin albumen and polyvinyl alcohol is different, is made Biocompatibility, mechanical performance, anti-microbial property and the degradation rate controllability of composite aquogel can be different.PH value contributes to Crosslinking degree and speed of the crosslinking agent to composite aquogel are adjusted, the degraded speed of composite aquogel can be controlled by adjusting pH value The pore size of rate and loose structure.
Preferably, the material of shaping is freezed 20~48 hours at -30~-40 DEG C.
Specifically, in being added to polyvinyl alcohol, the characteristics of, water miscible height is added in collagen fibroin albumen The shortcomings that molecular polyethylene alcohol and carboxymethyl chitosan can overcome homogenous material, so that biological response of synthetic materials used for keratoprosthesis both has There are good biocidal property, biocompatibility, there is excellent mechanical performance and degradation rate controllability.Referring specifically to Fig. 1, this hair The biological response of synthetic materials used for keratoprosthesis that bright embodiment provides be loose structure, including macropore and aperture, macropore diameter size for 200~ 500 μm, small aperture size is 1~10 μm.Perforating agent also includes polyethylene glycol and polyvinylpyrrolidone.Organic solvent also wraps Include methyl methacrylate.
Embodiment 1
(1) by carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, sodium chloride and organic solvent thionyl chloride in mass ratio: 0.5:2:1:5:10 ratios mix, and constant temperature stirs 2 hours under 85 DEG C of water-bath, by crosslinking agent Geniposide and fibroin albumen quality Than 0.5:10 take the Geniposide of certain mass, and add in mixture, adjust pH to 7.0, continue stirring 1 hour, obtain support Material blends, inject mould, pressing mold shaping;
(2) composite of shaping is freezed 10 hours at -20 DEG C, thawed 2 hours at room temperature;Repeated freezing-defrosting 5 It is secondary, porous composite aquogel is made;
(3) porous composite aquogel is placed in into sterile deionized water to soak 15 days, changes water daily twice, obtain artificial angle Membrane support material.
Embodiment 2
(1) carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent sodium chloride and organic solvent thionyl chloride are pressed Mass ratio:4:2:1:15:10 ratios mix, and constant temperature stirs 3 hours under 90 DEG C of water-bath, by crosslinking agent Geniposide and fibroin egg White mass ratio 1:8 take the Geniposide of certain mass, and add in mixture, adjust pH to 8.5, continue stirring 1.0 hours, obtain Timbering material mixture, inject mould, pressing mold shaping;
(2) composite of shaping is freezed 24 hours at -30 DEG C, thawed 5 hours at room temperature;Repeated freezing-defrosting 8 It is secondary, porous composite aquogel is made;
(3) porous composite aquogel is placed in into sterile deionized water to soak 10 days, changes water daily twice, obtain artificial angle Membrane support material.
Embodiment 3
(1) carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent sodium chloride and organic solvent thionyl chloride are pressed Mass ratio:1:2.5:2:15:20 ratios mix, and constant temperature stirs 2 hours under 85 DEG C of water-bath, by crosslinking agent Geniposide and fibroin Albumen quality is than 0.5:8 take the Geniposide of certain mass, and add in mixture, adjust pH to 9.0, continue stirring 0.5 hour, Timbering material mixture is obtained, injects mould, pressing mold shaping;
(2) composite of shaping is freezed 24 hours at -40 DEG C, thawed 4 hours at room temperature;Repeated freezing-defrosting 6 It is secondary, porous composite aquogel is made;
(3) porous composite aquogel is placed in into sterile deionized water to soak 30 days, changes water daily twice, obtain artificial angle Membrane support material.
Embodiment 4
(1) carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent sodium chloride and organic solvent thionyl chloride are pressed Mass ratio:5:3:2:20:20 ratios mix, and constant temperature stirs 2 hours under 85 DEG C of water-bath, by crosslinking agent Geniposide and fibroin egg White mass ratio 0.5:9 take the Geniposide of certain mass, and add in mixture, adjust pH to 8.5, continue stirring 1.5 hours, obtain Timbering material mixture is obtained, injects mould, pressing mold shaping;
(2) composite of shaping is freezed 24 hours at -30 DEG C, thawed 5 hours at room temperature;Repeated freezing-defrosting 8 It is secondary, porous composite aquogel is made;
(3) porous composite aquogel is placed in into sterile deionized water to soak 20 days, changes water daily twice, obtain artificial angle Membrane support material.
Embodiment 5
(1) carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent sodium chloride and organic solvent thionyl chloride are pressed Mass ratio:3:2:3:10:20 ratios mix, and constant temperature stirs 4 hours under 85 DEG C of water-bath, by crosslinking agent Geniposide and fibroin egg White mass ratio 1:6 take the Geniposide of certain mass, and add in mixture, adjust pH to 7.5, continue stirring 0.5 hour, obtain Timbering material mixture, inject mould, pressing mold shaping;
(2) composite of shaping is freezed 48 hours at -40 DEG C, thawed 6 hours at room temperature;Repeated freezing-defrosting 9 It is secondary, porous composite aquogel is made;
(3) porous composite aquogel is placed in into sterile deionized water to soak 30 days, changes water daily twice, obtain artificial angle Membrane support material.
Embodiment 6
(1) carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent sodium chloride and organic solvent thionyl chloride are pressed Mass ratio:2:2.5:1.5:10:10 ratios mix, under 85 DEG C of water-bath constant temperature stir 2.5 hours, by crosslinking agent Geniposide with Fibroin albumen quality is than 1:10 take the Geniposide of certain mass, and add in mixture, adjust pH to 8.0, and it is small to continue stirring 1.5 When, timbering material mixture is obtained, injects mould, pressing mold shaping;
(2) composite of shaping is freezed 48 hours at -26 DEG C, thawed 5 hours at room temperature;Repeated freezing-defrosting 4 It is secondary, porous composite aquogel is made;
(3) porous composite aquogel is placed in into sterile deionized water to soak 10 days, changes water daily twice, obtain artificial angle Membrane support material.
Embodiment 7
(1) carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent sodium chloride and organic solvent thionyl chloride are pressed Mass ratio:5:3:3:5:5 ratios mix, and constant temperature stirs 2 hours under 85 DEG C of water-bath, by crosslinking agent Geniposide and fibroin albumen Mass ratio 0.5:8 take the Geniposide of certain mass, and add in mixture, adjust pH to 9.0, continue stirring 0.5 hour, obtain Timbering material mixture, inject mould, pressing mold shaping;
(2) composite of shaping is freezed 36 hours at -26 DEG C, thawed 4 hours at room temperature;Repeated freezing-defrosting 9 It is secondary, porous composite aquogel is made;
(3) porous composite aquogel is placed in into sterile deionized water to soak 15 days, changes water daily twice, obtain artificial angle Membrane support material.
Embodiment 8
(1) carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent sodium chloride and organic solvent thionyl chloride are pressed Mass ratio:4:4:3:10:10 ratios mix, and constant temperature stirs 4 hours under 90 DEG C of water-bath, by crosslinking agent Geniposide and fibroin egg White mass ratio 1:5 take the Geniposide of certain mass, and add in mixture, adjust pH to 7.5, continue stirring 1.0 hours, obtain Timbering material mixture, inject mould, pressing mold shaping;
(2) composite of shaping is freezed 48 hours at -20 DEG C, thawed 6 hours at room temperature;Repeated freezing-defrosting 10 times, porous composite aquogel is made;
(3) porous composite aquogel is placed in into sterile deionized water to soak 30 days, changes water daily twice, obtain artificial angle Membrane support material.
Embodiment 9
(1) carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent sodium chloride and organic solvent thionyl chloride are pressed Mass ratio:1:3:3:20:15 ratios mix, and constant temperature stirs 3 hours under 90 DEG C of water-bath, by crosslinking agent Geniposide and fibroin egg White mass ratio 0.5:5 take the Geniposide of certain mass, and add in mixture, adjust pH to 7.0, continue stirring 1.5 hours, obtain Timbering material mixture is obtained, injects mould, pressing mold shaping;
(2) composite of shaping is freezed 36 hours at -30 DEG C, thawed 3 hours at room temperature;Repeated freezing-defrosting 7 It is secondary, porous composite aquogel is made;
(3) porous composite aquogel is placed in into sterile deionized water to soak 20 days, changes water daily twice, obtain artificial angle Membrane support material.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention All any modification, equivalent and improvement made within refreshing and principle etc., should be included in the scope of the protection.

Claims (9)

1. a kind of biological response of synthetic materials used for keratoprosthesis, it is characterised in that the material is composite aquogel, and the composite aquogel is more Pore structure, including:Carboxymethyl chitosan, fibroin albumen and polyvinyl alcohol, wherein, the carboxymethyl chitosan, the fibroin egg The mass ratio of polyvinyl alcohol described in bletilla is 0.5~5:2~10:1~4, the molecular weight of the polyvinyl alcohol is 1500~2000.
2. material according to claim 1, it is characterised in that the carboxymethyl chitosan is O-CMC, N- Carboxymethyl chitosan or at least one of N, O-CMC.
3. material according to claim 1, it is characterised in that the fibroin albumen is nanoscale silk fibroin powder or fibroin Protein solution.
4. a kind of preparation method of biological response of synthetic materials used for keratoprosthesis, it is characterised in that methods described includes:
Carboxymethyl chitosan, fibroin albumen, polyvinyl alcohol, perforating agent and organic solvent are mixed, and in 80~100 DEG C of water-bath Lower constant temperature adds crosslinking agent after stirring 2~4 hours, by the pH regulations of mixture to 7~9;
The mixture that pH value is 7~9 is injected into the shaping of bracket mould pressing mold, and the material of shaping is freezed at -20~-40 DEG C 10~48 hours, and thaw at room temperature, obtain the biological response of synthetic materials used for keratoprosthesis of porous composite aquogel;
Wherein, the molecular weight of the polyvinyl alcohol is 1500~2000, and the perforating agent is sodium chloride, and the organic solvent is two Chlorine sulfoxide, the crosslinking agent are Geniposide, the carboxymethyl chitosan, the fibroin albumen, the polyvinyl alcohol, the chlorination The mass ratio of sodium, the thionyl chloride and the Geniposide is 0.5~5:2~10:1~4:5~15:5~20:0.1~0.25.
5. according to the method for claim 1, it is characterised in that methods described also includes:
The material of the shaping is freezed at -20~-40 DEG C and thawed respectively three times at room temperature, obtains the artificial cornea Timbering material, wherein, cooling time is 10~48 hours, and thawing time is 2~6 hours.
6. according to the method for claim 4, it is characterised in that methods described also includes:
The biological response of synthetic materials used for keratoprosthesis is placed in aseptic deionized water and soaked 5~30 days.
7. according to the method for claim 4, it is characterised in that the perforating agent also includes polyethylene glycol or polyvinyl pyrrole Alkanone.
8. according to the method for claim 4, it is characterised in that the crosslinking agent also includes glutaraldehyde.
9. according to the method for claim 4, it is characterised in that organic solvent also includes methyl methacrylate.
CN201710774075.9A 2017-08-31 2017-08-31 A kind of biological response of synthetic materials used for keratoprosthesis and preparation method Pending CN107376009A (en)

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