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CN107875454A - A kind of collagen composite membrane for guide tissue regeneration and preparation method and application - Google Patents

A kind of collagen composite membrane for guide tissue regeneration and preparation method and application Download PDF

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Publication number
CN107875454A
CN107875454A CN201711208637.XA CN201711208637A CN107875454A CN 107875454 A CN107875454 A CN 107875454A CN 201711208637 A CN201711208637 A CN 201711208637A CN 107875454 A CN107875454 A CN 107875454A
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composite membrane
collagen composite
tissue regeneration
sis
matter powder
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CN107875454B (en
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翟晖
李伟峰
张玉兰
李湘杰
李次会
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Beijing Daqing Biotechnology Ltd By Share Ltd
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Beijing Daqing Biotechnology Ltd By Share Ltd
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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
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3629Intestinal tissue, e.g. small intestinal submucosa
    • 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
    • A61L27/02Inorganic materials
    • A61L27/025Other specific inorganic materials not covered by A61L27/04 - A61L27/12
    • 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
    • A61L27/02Inorganic materials
    • A61L27/12Phosphorus-containing materials, e.g. apatite
    • 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
    • A61L27/54Biologically 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/112Phosphorus-containing compounds, e.g. phosphates, phosphonates
    • 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
    • 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
    • A61L2300/412Tissue-regenerating or healing or proliferative 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • A61L2300/608Coatings having two or more layers

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Abstract

The present invention relates to a kind of collagen composite membrane for guide tissue regeneration and preparation method thereof, the composite membrane is to be evenly applied to be made on SIS thin-film materials by the bioactive minerals matter powder;The collagen composite membrane can be multilayer, including following component:SIS thin-film materials, bioactive minerals matter powder.Collagen composite film-strength prepared by the present invention is high, and histocompatbility is good, also with natural bacteriostatic characteristic, is with a wide range of applications in dental care field.

Description

A kind of collagen composite membrane for guide tissue regeneration and preparation method and application
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of collagen composite membrane and its system for guide tissue regeneration Preparation Method and application.
Background technology
Guide tissue regeneration (guided tissue regeneration, GTR) is Periodontics research in the late two decades One of lasting focus.Its general principle is exactly to prevent gingival epithelium root to growth using barrier film, while prevents gum connective Histocyte contacts with root face, maintains certain space so that periodontal ligament cell occupies root face, and it is newly attached that differentiation and proliferation forms periodontal .GTR technologies are all proved to be able to obtain different degrees of regeneration in human body and animal body, are opened from the eighties in 19th century Begin to be applied to treatment periodontitis, achieve preferable clinical effectiveness.
The key of GTR technical research, it is the research to GTR membrane materials.Material applied to GTR technologies must possess barrier Property and guiding particular organization regeneration function.The guide tissue regeneration film clinically applied can be divided into according to raw material to drop Solve absorbing film and degradable absorbing film.Non-degradable, which absorbs GTR films, mainly titanium film and expanded polytetrafluoroethylsealing (e-PTFE) film, It has advantages below:Membrane material is stable, good biocompatibility;There are stronger mechanical strength and space to maintain ability;Can be any The holdup time in vivo is adjusted, complication occur can remove in time.But its shortcoming is also apparent:Film is not fixed easily;It is easily caused The appearance of the complication such as mucous membrane splits, film exposure, infection;Need second operation to extract, easily to tissue cause to damage, influence continue into The effect of bone.
Because non-degradable absorbs the inherent shortcoming of GTR films, biodegradable absorbing material turns into GTR technical research gradually Important directions.Late 1980s, after biodegradable idea occurs, degradable absorption membrane material is introduced, they incline To in the second operation for saving taking-up film, treatment time is shortened, ensure that periodontosis tissue regeneration processes are not interrupted, is studied Scholars think that at least from the perspective of periodontal scholar degradable absorbing film is better than non-degradable absorbing film, and clinical effect Fruit is suitable with non-degradable absorbing film or more preferable, so turning into guide tissue regeneration film technology using biodegradable absorbing film A kind of general development trend.
Generally acknowledged preferable degradable absorption GTR films should possess following condition:(1) with good biocompatibility and carefully Born of the same parents' compatibility;(2) film has certain isolation effect, fibroblast can be prevented to permeate;(3) degradation rate of film is controllable, and with The regeneration of tissue is mutually coordinated;(4) catabolite has no adverse reaction in vivo, and the degradation process of film does not influence regeneration;(5) Film has certain mechanical strength, pliability and operability.
Studying more degradable resorbable membrane at present mainly has artificial synthesized high polymer material and the major class of natural material two. Artificial synthesized high polymer material includes PLA, linear aliphatic polyesters polyvinyl alcohol etc.;Natural macromolecular material include collagen, Chitosan etc..GTR films prepared by the artificial synthesized high molecular polymer using PLA, polyglycolic acid as representative, in vivo can be with Degraded absorbs, but can produce slightly sour environment after degraded in vivo, causes inflammatory reaction, is unfavorable for organization healing.Collagen, shell gather GTR films prepared by the natural polymerses such as sugar, harmful substance will not be produced after degradation in vivo, biocompatibility is better than people Work synthesized degradable high molecular polymer, but the mechanical performance of the film of natural polymerses preparation and water-resistance are poor, drop Solve it is too fast, with bone growth speed mismatch.
CN200410071932.1 discloses a kind of double-layer collagen base guide tissue regeneration material and preparation method thereof, is gram The defects of collagen-based materials degraded is too fast is taken, it improves the anti-degradation capability of material using chemical cross-linking agent, but glutaraldehyde etc. is changed The toxicity of crosslinking agent is larger, and the elution process after crosslinking is not easy to, and the residual of the crosslinking agent not eluted in the body can be made The injury of paired human body.
Submucous layer of small intestine (Small Intestinal Submucosa, SIS) is a kind of degradable native biological Material, there is prominent biological superiority in terms of tissue repair and regeneration.The technology of preparing of SIS materials contains substantially to disappear The steps such as poison, virus removal, machinery divest, degreasing, de- cell, de-sludging, drying and sterilizing.By rationally treated SIS materials It is that one kind can be with inducing tissue regeneration, the thin-film material of low immunogenicity.
The content of the invention
It is an object of the invention to provide a kind of collagen composite membrane for guide tissue regeneration and preparation method thereof, the present invention Collagen composite film-strength is high, and histocompatbility is good, also with natural bacteriostatic characteristic, is had a wide range of applications in dental care field Prospect.
Technical solution of the present invention is as follows:
A kind of collagen composite membrane for guide tissue regeneration, including following component:SIS thin-film materials, bioactivity ore deposit Material powder.
Specifically, the bioactive minerals matter powder account for the percentage by weight of the collagen composite membrane for 0.01%~ 50%, preferably 1%~30%.
The SIS thin-film materials can be made by existing conventional techniques, such as the method that CN101433735A is recorded.
Usually, the preparation method of the SIS thin-film materials includes via intestinal tube axially cuing open submucous layer of small intestine material Open, and circumferentially cut into the rectangle SIS units of arbitrary dimension, retain the ring natural width of intestinal tube, then sterilized, The steps such as degreasing, de- cell, de-sludging processing are made.
Preferably, the bioactive minerals matter powder, the composition containing following percentage by weight:SiO240-65%, CaO 15-30%, Na2O 15-30%, P2O52-8%;Further, its particle size range is less than 90 μm, wherein, contain aperture Quasi-nano particle 0.1-20.0wt% in the range of 100-900nm.
Preferably, the bioactive minerals matter powder, the composition containing following percentage by weight:SiO245-61%, CaO 17-27%, Na2O 19-25%, P2O52.6-6%;Further, its particle size range is less than 90 μm, wherein, contain hole Quasi-nano particle 2-10% of the footpath in the range of 100-900nm.
It is further preferred that the bioactive minerals matter powder, the composition containing following percentage by weight:SiO2 45%, CaO 24.5%, Na2O 24.5%, P2O56%;Further, its particle size range is less than 90 μm, wherein, contain aperture Quasi-nano particle 2-5% in the range of 100-900nm.
In above-mentioned bioactive minerals matter powder, the raw material of silica is silica;The raw material of calcium oxide is carbonic acid Calcium;The raw material of sodium oxide molybdena is sodium carbonate;The raw material of phosphorus pentoxide is phosphorus pentoxide.
Above-mentioned bioactive minerals matter powder can be made by existing conventional techniques, such as the side that CN102826752A is recorded Method.
Specifically, the collagen composite membrane of the present invention for guide tissue regeneration, it is by the bioactive minerals matter Powder is evenly applied to be made on SIS thin-film materials.
In the present invention, it is defined as with SIS thin-film materials and the bioactive minerals matter powder coated thereon described One layer of collagen composite membrane.
The collagen composite membrane can be multilayer, preferably 1-14 layers, more preferably 4-12 layers, more preferably 6-10 Layer.
Further, the weight of the bioactive minerals matter powder coated in every layer and the SIS thin-film materials Ratio is 1:(1-99), preferably 1:(1-49);Such as 1:99、1:50、1:30、1:5.
Further, crossed orientation arranges between every layer of SIS thin-film materials, and the SIS thin-film materials of even a certain layer are Axially, then one layer adjacent of SIS thin-film materials are ring.
Further, the superiors of the collagen composite membrane are that multilayer (being preferably 1-4 layers) SIS thin-film materials (do not apply Cover the bioactive minerals matter powder);Further, crossed orientation arranges between these multilayers SIS thin-film materials, even A certain layer SIS thin-film materials is axially, then one layer of adjacent SIS thin-film material are ring.
Because the axial direction of submucous layer of small intestine is different with the mechanical property of ring, intersects tiling and be beneficial to compound film dynamic performance Be uniformly distributed.
The present invention also provides a kind of preparation method of such as above-mentioned collagen composite membrane for guide tissue regeneration, this method Comprise the following steps:
(1) SIS thin-film materials (generally rectangle, approximate rectangle etc.) are taken to be laid on smooth flat board;
Usually, the flat board is made up of alloy materials such as high polymer material or stainless steels;
(2) above-mentioned bioactive minerals matter powder is evenly applied to the SIS thin-film material surfaces;Or by above-mentioned biology Active mineral matter powder is uniformly mixed in gel systems in advance, and the mass fraction that bioactive minerals matter powder is made is 0.1%-20% hydrogel (being preferably the hydrogel that mass fraction is 5%-10%), then will contain bioactive minerals matter The hydrogel of powder is evenly applied to the SIS thin-film material surfaces;
Wherein, the gel systems can be dissolved in the water by degradable water soluble macromolecular material and are prepared, institute It can be hyaluronic acid, water soluble chitosan, collagen, gelatin etc. to state degradable water soluble macromolecular material;
Further, the weight of the bioactive minerals matter powder coated in every layer and the SIS thin-film materials Ratio is 1:(1-99), such as 1:99、1:50、1:10、1:5;
(3) it is another to take SIS thin-film materials to be laid in the bioactive minerals matter powder layer of step (2) preparation;By step Suddenly (2) identical method coats the bioactive minerals matter powder;
Further, crossed orientation arranges between every layer of SIS thin-film materials, and the SIS thin-film materials of even a certain layer are Axially, then one layer adjacent of SIS thin-film materials are ring;
(4) collagen composite membrane for guide tissue regeneration of the different numbers of plies can be prepared (such as by repeating above step Shown in Fig. 1).
The number of plies can be multilayer, preferably 1-14 layers, more preferably 4-12 layers, more preferably 6-10 layers.
Further, the above method also include will be prepared described in be used for guide tissue regeneration collagen composite membrane carry out Dry step.
The drying means can be various conventional drying methods, such as hot dry, vacuum drying, air-dried, lyophilized or do naturally It is dry.
Further, present invention research is found, by controlling drying condition to control each of the collagen composite membrane Layer or several layers of compound fine and close porousnesses.Each layer of different fine and close porousnesses, which is combined with each other, can obtain all size Collagen composite membrane, such as the two-sided collagen composite membrane that the fine and close another side of one side is loose.
Specifically, a kind of drying means is dry (for example with drying box) for heat, and temperature can be set to 25-40 DEG C, drying time 8-36h;Another drying means is alternatively lyophilized.
Preferably to improve the performance of the collagen composite membrane, SIS thin-film materials can also be done to further feature and changed Property.
Specifically, SIS thin-film materials are soaked in modifying agent in advance before laying, SIS surfaces is carried active amino Or polycation, obtain functional film component;The modifying agent is selected from polylysine, polylysine-aspartic acid copolymer Or the one or more in chitosan solution.Pass through polylysine, polylysine-aspartic acid copolymer or chitosan surface band Some active amino or positive charge assign material bilateral different features, obtain that toxicity is low, and cell compatibility is good, has function The tissue renovation material of property.
The total concentration scope of the modifying agent is 0.001%-40%, because the total concentration of modifying agent is relevant with molecular weight, As molecular weight is low, then modifier concentration accordingly improves, and it is suitable that those skilled in the art can select according to the professional general knowledge grasped Modifier molecules amount and concentration, preferably 0.001%-32%;Active ingredient can mix in any proportion in this concentration range; The soak time is 10min-24h, preferred scope 1h-4h;Preferably, the modifying agent is polylysin solution, its concentration For 0.5%, 2h is soaked;The polylysine or polylysine-aspartic acid copolymer molecular weight are 1000-100000, described Chitosan molecule amount is 3000-200000.
It is above-mentioned to have the advantages that SIS thin-film material modifications:
1st, the native three dimensional structure of de- extracellular matrix is maintained, is advantageous to growth, propagation and the differentiation of cell.
2nd, the active amino that modifying agent polylysine, polylysine-aspartic acid copolymer or chitosan surface carry, by Its SIS composite after handling can promote creeping and growing for cell, can be used as guide tissue regeneration material and guiding bone Regrown material.
Present invention additionally comprises the collagen composite membrane for guide tissue regeneration prepared by the above method.
Present invention additionally comprises the above-mentioned collagen composite membrane for guide tissue regeneration to prepare with guide tissue regeneration Application in terms of functional material.
The present invention is used for the collagen composite membrane of guide tissue regeneration or the functional material with guide tissue regeneration can For fields such as oral cavity, orthopaedics.
Viscosity of the present invention can be detected by this area conventional method, such as according to《Chinese Pharmacopoeia》Crow in (2015 editions) Family name's viscometer method detects.
Provided by the present invention for the collagen composite membrane of guide tissue regeneration therapeutic effect be specifically described it is as follows:
1st, composite membrane provided by the invention can be used for guide tissue regeneration.The present invention is SIS materials and bioactive minerals The composite membrane of matter powder, the wherein one side of SIS materials can effectively stop soft tissue, and guiding soft tissue prevents along film surface growth Soft tissue is too fast to grow into skeletonization region, and good barrier action is provided for osteanagenesis, maintains space needed for osteanagenesis;It is in vivo Degradation speed is 2-6 months, and the support of enough time is provided for osteanagenesis;Meanwhile it is compounded with bioactive minerals matter powder Simultaneously, because bioactive minerals matter powder has the activity of unique bone induction and regeneration, osteoblastic proliferation can be promoted, accelerated Knitting.
2nd, the present composition can be used for guiding bone regeneration while oral cavity implanting tooth, be planted at once after extraction Bone regeneration around implant guided bone regeneration, bone after bone regeneration around implant guided bone regeneration, extraction during plant during progress extension implant Guided bone regeneration, local alveolar ridge augmentation, alveolar ridge amplification art, the radectomyl radiectomy in Lie Xing Cranial defects area, oral cavity tumour The filling in the Cranial defect region after resection and undesirable root arrachement, periodontal bone defects etc..Also can combine with various bone fillers makes With.
3rd, can prevent while composition guide tissue regeneration provided by the invention in art or postoperative infection.Quasi-nano is given birth to Thing active mineral matter powder has broad-spectrum antibacterial, can suppress intraoral Actinobacillus, streptococcus, porphyromonas gingivalis, The oral cavity pathogens such as Prevotella intermedia, treponema denticola, Post operation is neutralized due to thin so as to which said composition can prevent operation Microbial infection.
The present invention has advantages below:
1st, SIS materials and bioactive minerals matter the powder combination that composition provided by the invention uses, said composition is not Only bootable regeneration, while Bone Defect Repari is can induce, it is specific as follows:Bioactive minerals matter powder and SIS in said composition In collagenous fibres combine, into after human body defect, along with the degraded of SIS materials, bioactive minerals matter powder delays On The Drug Release, bioactive minerals matter powder is with after bioresorbable, ion exchange can occur immediately in its particle surface, so as in bone The apatite gel layer containing bicarbonate is produced with bioactive minerals matter powder surface, Self substances can be considered by body And received, and then the autocrine mediated response of osteocyte is stimulated, cytokine profiles are produced, finally cause the rapid propagation of bone.Separately Outside, HCA generation can cause the precipitation of collagenous fibres, thus caused collagen can be precipitated constantly in SIS degradation process, Multiple bone islands are gradually formed with autologous bone and collagenous fibres under the stimulation of cell factor, these bone islands are further connected, most After complete Bone Defect Repari.Thus simultaneously non-individual works the material of the present composition, but is sent out in bioactive minerals matter powder After raw ion exchange forms HCA, complement one another, so as to realize faster reparation, while there is osteoinductive.
2nd, SIS promotes endogenous tissue regenerative process in vivo, realizes the reproducibility reparation to defect, and SIS is mainly day So, the collagen component of degradable absorption, there is low antigenicity, good histocompatbility and mechanical compliance;SIS pollution or Infected zone early promotion new vessels is formed, and enhancing tissue is to the tolerance that pollutes and infect.;Bioactive minerals matter powder With bacteriostasis, suppress common pathogen in oral cavity, surgical site infection risk can be greatly reduced in the two combination.
3rd, the present invention provides the preparation method for preparing said composition, SIS bioactive minerals matter powders for thin-film material For solid powder, mode is not used in combination well clinically.Preparation method resulting composition provided by the invention is thin Membranaceous, soft texture, bioactive minerals matter powder complements each other with SIS materials and combined closely, and facilitates Clinical practice.It is and compound The SIS materials of bioactive minerals matter powders make guide tissue regeneration film be provided with preferably promote the effect of skeletonization with it is good Anti-infectious function.
4th, compared to the guide tissue regeneration collagem membrane being directly prepared into by collagen, new guiding tissue provided by the invention is again Filming has good mechanical strength, and the mechanical strength of cladding SIS films is prepared according to the preparation method of invention description, can meet to draw Lead the Clinical practice requirement of regeneration art.
Brief description of the drawings
Fig. 1 is the structural representation for the collagen composite membrane that the present invention is used for guide tissue regeneration;
Wherein, 1 is SIS film material plies, and 2 are biological active mineral matter powder layer or contain bioactive minerals matter powder Gel layer;
Fig. 2 is the experimental result picture of experimental example 1.
Fig. 3 is the scanning electron microscope (SEM) photograph for the collagen composite membrane that embodiment 1 is used for guide tissue regeneration;
It is surface partial enlarged drawing wherein to scheme A, and figure B is sectional drawing, and figure C is SIS collagenous fibres enlarged drawings.
Embodiment
Following examples are used to illustrate the present invention, but are not limited to the scope of the present invention.It is unreceipted specific in embodiment Technology or condition person, carried out according to the technology or condition described by document in the art, or according to product description.It is used Reagent or the unreceipted production firm person of instrument, it is the conventional products that can be commercially available by regular distributor.
It is prepared by the method that SIS thin-film materials as described below are recorded by CN101433735A embodiments 1.
Bioactive minerals matter powder as described below, the composition containing following percentage by weight:SiO245%, CaO 24.5%, Na2O 24.5%, P2O56%;Further, its particle size range is less than 90 μm, wherein, containing aperture in 100- Quasi-nano particle 2-5% in the range of 900nm;It is prepared by the method that can be recorded by CN102826752A.
Embodiment 1
A kind of collagen composite membrane for guide tissue regeneration, its preparation method comprise the following steps:
(1) SIS thin-film materials are taken to be laid on smooth flat board;The flat board is by high polymer material or stainless steel etc. Alloy material is made;
(2) above-mentioned bioactive minerals matter powder is uniformly mixed in gel systems in advance, bioactive minerals is made The mass fraction of matter powder is 10% hydrogel, then uniformly applies the hydrogel containing bioactive minerals matter powder It is overlying on the SIS thin-film material surfaces;
Wherein, the gel systems can be dissolved in the water by degradable water soluble macromolecular material and are prepared, institute It can be hyaluronic acid to state degradable water soluble macromolecular material;The coated bioactive minerals matter powder in every layer Part by weight with the SIS thin-film materials is 1:10;
(3) it is another to take SIS thin-film materials to be laid in the bioactive minerals matter powder layer of step (2) preparation;By step Suddenly (2) identical method coats the bioactive minerals matter powder;
(4) above step is repeated, crossed orientation arranges between making every layer of SIS thin-film materials, and the SIS of even a certain layer is thin Membrane material is axially, then one layer adjacent of SIS thin-film materials is ring;Prepare the number of plies be 6 layers it is described be used for guide The collagen composite membrane (as shown in Figure 1) of regeneration.Required product can be obtained by being dried again.
Embodiment 2
A kind of collagen composite membrane for guide tissue regeneration, its preparation method differ only in embodiment 1:Step 2) above-mentioned bioactive minerals matter powder is uniformly mixed in gel systems in advance, the matter of bioactive minerals matter powder is made The hydrogel that fraction is 20% is measured, is then evenly applied to the hydrogel containing bioactive minerals matter powder described SIS thin-film material surfaces;The weight ratio of the coated bioactive minerals matter powder and the SIS thin-film materials in every layer Example is 1:50.
Embodiment 3
A kind of collagen composite membrane for guide tissue regeneration, its preparation method differ only in embodiment 1:Step 2) above-mentioned bioactive minerals matter powder is uniformly mixed in gel systems in advance, the matter of bioactive minerals matter powder is made The hydrogel that fraction is 30% is measured, is then evenly applied to the hydrogel containing bioactive minerals matter powder described SIS thin-film material surfaces;The weight ratio of the coated bioactive minerals matter powder and the SIS thin-film materials in every layer Example is 1:30.
Embodiment 4
A kind of collagen composite membrane for guide tissue regeneration, its preparation method differ only in embodiment 1:Step 2) above-mentioned bioactive minerals matter powder is uniformly mixed in gel systems in advance, the matter of bioactive minerals matter powder is made The hydrogel that fraction is 50% is measured, is then evenly applied to the hydrogel containing bioactive minerals matter powder described SIS thin-film material surfaces;The weight ratio of the coated bioactive minerals matter powder and the SIS thin-film materials in every layer Example is 1:5.
Comparative example 1
A kind of composite membrane, with differing only in for embodiment 1:Bioactive minerals matter powder and the SIS thin-film materials Simple physical is mixed, and powder is applied into SIS material surfaces.
Comparative example 2
A kind of composite membrane, with differing only in for embodiment 1:The coated bioactive minerals matter powder in every layer Part by weight with the SIS thin-film materials is 1:0.5.
Comparative example 3
A kind of composite membrane, with differing only in for embodiment 1:The coated bioactive minerals matter powder in every layer Part by weight with the SIS thin-film materials is 1:100.
Experimental example 1:Guide tissue regeneration film animal experiment
Experiment material:Collagen composite membrane for guide tissue regeneration prepared by embodiment 1, comparative example 1 are prepared compound Film;
Experimental method:Using the rabbit of mandibular defect as experimental subjects, above-mentioned experiment material is guided into regeneration reality Test.
Experimental result:As shown in Fig. 2 the collagen composite membrane of embodiment 1 be used for defect after eight weeks defect be cured substantially Close, and the composite membrane of comparative example 1 still has 4mm × 2mm irregular defect.Show, guide tissue regeneration significant effect of the present invention.
The guide tissue regeneration film mechanical strength of experimental example 2
The regeneration membrane respectively prepared by embodiment 1-4 and comparative example 1-3 carries out mechanical strength test.
Each regeneration membrane is cut into 1.5cm × 5cm strips, is sandwiched in mechanical test instrument test section, carries out tensile strength survey Examination, draw speed 1mm/min.Method of testing is detection method commonly used in the art.
Test result such as following table:Unit N/cm
As a result show, guide tissue regeneration film mechanical strength prepared by the present invention is much larger than like product, more preferable to meet to face Bed demand.
Experimental example 3
The scanning electron microscope (SEM) photograph of collagen composite membrane for guide tissue regeneration prepared by embodiment 1 is shown in Fig. 3, can from sectional drawing Being clearly visible guide tissue regeneration film has double-layer structure, and its loose one side is amplified, a fixed number is combined on its collagenous fibres The bioactive minerals matter powder of amount.

Claims (10)

1. a kind of collagen composite membrane for guide tissue regeneration, it is characterised in that be that bioactive minerals matter powder is uniform Coated on manufactured multilayer film on SIS thin-film materials;
The percentage by weight that the bioactive minerals matter powder accounts for the collagen composite membrane is 0.01%~50%;
The bioactive minerals matter powder, the composition containing following percentage by weight:SiO240-65%, CaO 15-30%, Na2O 15-30%, P2O52-8%, its particle size range are less than 90 μm, wherein, the standard containing aperture in the range of 100-900nm Nano-scale particle 0.1-20.0wt%.
2. it is used for the collagen composite membrane of guide tissue regeneration according to claim 1, it is characterised in that the bioactivity ore deposit The percentage by weight that material powder accounts for the collagen composite membrane is 1%~30%.
3. the collagen composite membrane according to claim 1 or claim 2 for guide tissue regeneration, it is characterised in that the collagen is answered Conjunction film is 1-14 layers, preferably 4-12 layers, more preferably 6-10 layers.
4. it is used for the collagen composite membrane of guide tissue regeneration according to claim any one of 1-3, it is characterised in that in every layer The part by weight of the coated bioactive minerals matter powder and the SIS thin-film materials is 1:(1-99), preferably 1: (1-49)。
5. it is used for the collagen composite membrane of guide tissue regeneration according to claim any one of 1-4, it is characterised in that every layer Crossed orientation arranges between SIS thin-film materials;
Preferably, the superiors of the collagen composite membrane are multilayer SIS thin-film materials;It is highly preferred that these multilayers SIS film materials Crossed orientation arranges between material.
6. it is used for the collagen composite membrane of guide tissue regeneration according to claim any one of 1-5, it is characterised in that the life Thing active mineral matter powder, the composition containing following percentage by weight:SiO245-61%, CaO 17-27%, Na2O 19- 25%, P2O52.6-6%;Further, its particle size range is less than 90 μm, wherein, containing aperture in the range of 100-900nm Quasi-nano particle 2-10%;
Preferably, the bioactive minerals matter powder, the composition containing following percentage by weight:SiO245%, CaO 24.5%, Na2O 24.5%, P2O56%;Further, its particle size range is less than 90 μm, wherein, containing aperture in 100- Quasi-nano particle 2-5% in the range of 900nm.
7. it is used for the collagen composite membrane of guide tissue regeneration according to claim any one of 1-6, it is characterised in that described Modified dose of immersion is modified SIS thin-film materials in advance, SIS surfaces is carried active amino or polycation;The modifying agent choosing One or more from polylysine, polylysine-aspartic acid copolymer or chitosan solution.
8. it is used for the preparation method of the collagen composite membrane of guide tissue regeneration described in claim any one of 1-7, it is characterised in that Comprise the following steps:
(1) SIS thin-film materials are taken to be laid on smooth flat board;
(2) bioactive minerals matter powder is evenly applied to the SIS thin-film material surfaces;Or by above-mentioned bioactive minerals Matter powder is uniformly mixed in gel systems in advance, and the mass fraction that bioactive minerals matter powder is made is 0.1%-50%'s Hydrogel, the hydrogel containing bioactive minerals matter powder is then evenly applied to the SIS thin-film material surfaces;
Wherein, the gel systems can be dissolved in the water by degradable water-soluble high-molecular material and are prepared, described to drop It can be hyaluronic acid, water soluble chitosan, collagen, gelatin to solve water-soluble high-molecular material;
(3) it is another to take SIS thin-film materials to be laid in the bioactive minerals matter powder layer of step (2) preparation;By step (2) Identical method coats the bioactive minerals matter powder;
(4) collagen composite membrane for guide tissue regeneration of the different numbers of plies can be prepared by repeating above step.
9. preparation method according to claim 8, it is characterised in that also include will be prepared described in be used for guide tissue The step of collagen composite membrane of regeneration is dried;The drying is dry for heat, and temperature is 25-40 DEG C, drying time 8-36h;Or Drying means described in person is lyophilized.
10. the collagen composite membrane for guide tissue regeneration or the side of claim 8 or 9 described in claim any one of 1-7 Collagen composite membrane for guide tissue regeneration prepared by method answering in terms of the functional material with guide tissue regeneration is prepared With.
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