CN103191085A - Double-layer composite regeneration film and making method thereof - Google Patents
Double-layer composite regeneration film and making method thereof Download PDFInfo
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Abstract
The invention relates to a double-layer composite regeneration film and a making method thereof. The regeneration film comprises a compact layer and a loose layer, the compact layer is formed through compounding a degradable high-molecular fiber web with a collagen film, or with collagen and nano-silver particles, or with collagen and a medicine having a treatment effect, and the loose layer is formed by treating one or more selected from chitosan, silk fibroins, keratoprotein and collagens as a matrix material. The preparation method mainly comprises a step of preparing the fiber strengthened compact layer, a step of preparing the loose layer, and a step of preparing a guide film through compounding. The regeneration film has the advantages of good biocompatibility and mechanical performances, biodegradability, low immune rejection response, simple operation and the like, and can be widely used for restoring tissues, especially bone tissues and periodontal tissues.
Description
Technical field
The present invention relates to guide tissue regeneration film of a kind of biomedical materials field and preparation method thereof, this material can be used for the reparation of defective tissue, especially the reparation of osseous tissue and periodontal tissue.
Background technology
(guided tissue regeneration GTR) has been widely used in the periodontal surgery, is considered to cause the effective means of periodontal tissue's physiological regeneration in guided tissue regeneration.At present, the membrane material for guided tissue regeneration is divided into degradable membrane material and non-degradable membrane material two classes.Though the non-degradable membrane material has excellent biological compatibility and mechanical property, and obtain certain curative effect, can not be organized absorption, need second operation to take out, increased patient's misery, so do not accepted by the patient.The biodegradable membrane material optionally guides defective tissue regeneration because it has, and Wholly-degradable, does not need advantages such as second operation, facilitating operation, is attracted attention.But the biodegradable membrane material of prior art all can't satisfy the requirement of osseous tissue and periodontal tissue's defect repair in problems such as mechanical property, degradation property, biological activitys.
Summary of the invention
The technical problem that the present invention solves provides a kind of two-layer compound guiding regeneration membrane and preparation method thereof, to improve the biological activity of guiding film, promotes the healing of wound, improves its mechanical property, for the tissue defect reparation provides a kind of new membrane material.
The present invention adopts following technical scheme: a kind of two-layer compound regeneration membrane, comprise compacted zone and weaker zone, and it is characterized in that: described compacted zone is composited by degradable macromolecule fleece and collagem membrane.
Be compounded with nano silver particles and/or medicine in the described collagem membrane; Described weaker zone is by being selected from chitosan, fibroin albumen, and keratoprotein, or in the collagen protein one or more form as matrix material.
Described compacted zone is that degradable macromolecule fleece and collagem membrane alternately are layering, and the superiors and orlop are collagem membrane, and thickness is 0.5 ~ 2mm; Contain a certain amount of hyaluronic acid that is selected from the described weaker zone, chondroitin sulfate, calcium salt, or one or several formation in the bone morphogenic protein BMP-2 somatomedin.
Further, the fibroreticulate material of described degradable macromolecule is selected from the medical grade polydioxanone, polylactic acid, poly (glycolide-lactide), polycaprolactone, the combination of one or more in poly-(3-butyric ester-3-hydroxyl valerate).
Further, described medicine is selected from one or more the combination in paclitaxel, amycin, streptomycin, cefradine, gentamycin, acetylspiramycin, erythromycin, albomycin, amoxicillin, oxytetracycline, kanamycin, penicillin, metronidazole, danshensu, neomycin, ribostamycin, tetracycline, vancomycin, the azithromycin.
The present invention also provides the preparation method of described two-layer compound regeneration membrane, mainly may further comprise the steps:
Step 1, the preparation of fiber reinforcement compacted zone, step 1 further comprises following technology:
Form collagen solution with organic acid dissolving collagen, collagen solution is injected in the mould, lyophilization then, preparation collagen sponge membrane;
Become net as enhancement layer with degradable macromolecule fibrage; And
The collagen sponge membrane for preparing and the degradable macromolecule fiber web layer system of laminating is formed compacted zone by the compound degradable medical macromolecular fibre enhancing of degradable macromolecule fleece and collagem membrane;
Step 2, the preparation of weaker zone, step 2 further comprises following technology:
Be selected from chitosan with the organic acid dissolving, fibroin albumen, keratoprotein, one or more in the collagen protein polymer form solution; And
The solution of gained is injected mould, lyophilization then, preparation weaker zone collagen sponge;
Step 3, compacted zone and weaker zone are compounded to form the two-layer compound regeneration membrane.
Wherein, in the step 1, described collagen solution is type i collagen albumen, or contains a small amount of III collagen type in the type i collagen albumen and be dissolved in the solution that forms in the organic acid; Further be compounded with medicine and/or nano silver particles in the described collagen solution.
Further, in the step 1, the mass volume ratio concentration range of collagen solution is 0.1 ~ 2%, and viscosity coefficient is 1000 ~ 4000cp; Be 10 in drug concentrations described in the collagen solution
-3~ 20mmol/L, the concentration of nanometer silver is 40 ~ 800ppm; Collagen sponge membrane and degradable macromolecule fiber web layer poststack, the superiors and orlop are collagen sponge membrane, put into the certain thickness compacted zone of compacting formation between the flat board then.
In the step 2, described solution injects the before further compound a certain amount of hyaluronic acid that is selected from of mould, sulfate composite chrondroitin, calcium salt, one or more materials in the BMP somatomedin; The mass volume ratio concentration of chitosan described in the solution is 0.1 ~ 3%, the mass volume ratio concentration of fibroin albumen is 0.2 ~ 5%, the mass volume ratio concentration of keratoprotein is 0.1 ~ 8%, the mass volume ratio concentration of collagen protein polymer is 0.1 ~ 2%, hyaluronic mass volume ratio concentration is 0.05 ~ 1.5%, the mass volume ratio concentration of chondroitin sulfate is 0.05 ~ 0.3%, and the mass volume ratio concentration of calcium salt is 0.05 ~ 3%; The mass volume ratio concentration of BMP somatomedin is 0.00001 ~ 0.015%.
In the step 3, be with the fiber reinforcement compacted zone carry out high-temperature cross-linking, weaker zone carries out high-temperature cross-linking and chemical crosslinking, then crosslinked weaker zone is cleaned lyophilization; Carry out the compound of compacted zone and weaker zone at last, thereby obtain the two-layer compound regeneration membrane; The compound operational approach of compacted zone and weaker zone is the prepared collagen solution of one side coating one deck step 1 at compacted zone, puts weaker zone, lyophilization then.
The invention has the beneficial effects as follows:
Two-layer compound guiding regeneration membrane material of the present invention, be used for osseous tissue, the new medical membrane material of tissue repair such as dental tissue, this film has following characteristics: (1) adopts biocompatibility and biodegradable high molecular polymer to prepare guiding film, tissue reaction is little, can not cause organism immune response and confirmatory reaction; (2) adding of therapeutic effect medicine is arranged, promote the healing effect of wound; (3) fibroreticulate adding improves the mechanical strength of guiding film, and degradation time is controlled.
Further, the guiding film that the adding of inorganic constituents and BMP somatomedin increases become bone bioactivity, promote osteoblastic growth.
Facts have proved that the compound guiding film of the present invention preparation has good biological activity, antibiotic property, mechanical strength preferably, degradation rate is adjustable, promotes advantages such as wound healing, degradation in vivo or be 4 ~ 12 months by the time that body absorbs fully.Adopt GB/T 528 to test, the fracture tensile strength of this film under hygrometric state is 5 ~ 40MPa.Adopting national standard test cell toxicity is 0 grade.This MULTILAYER COMPOSITE regeneration membrane is applied to the reparation of the reparation of defective tissue, particularly osseous tissue and dental tissue, has broad application prospects.
The specific embodiment
Two-layer compound regeneration membrane of the present invention mainly is as the Oral Repair film, is a kind of guide tissue regeneration film, and it is made up of fibre-reinforced compacted zone and weaker zone.Described compacted zone is formed by degradable macromolecule fleece composite collagen film, the further medicine of dopen Nano silver particles and/or therapeutic effect in the described collagen.Weaker zone is by chitosan, or fibroin albumen, or keratoprotein, or collagen protein etc. is matrix material, further compound a certain amount of hyaluronic acid, or sulfate composite chrondroitin, or compound a certain amount of calcium salt, or one or more formations in bone morphogenetic protein (BMP) factor.
This fiber reinforcement compacted zone alternately is layering by degradable macromolecule fleece and collagem membrane, preferably, the superiors and orlop are collagem membrane, put into afterwards between two flat boards, prepare certain thickness with certain mechanical force compacting a period of time, as the compacted zone of 0.5 ~ 2mm.
The fibroreticulate material of degradable macromolecule in this fiber reinforcement compacted zone is selected from medical grade polydioxanone (PDO), or polylactic acid (PLA), or poly (glycolide-lactide) (PLGA), polycaprolactone (PCL), or poly-(3-butyric ester-3-hydroxyl valerate) (PHBV), or its analog, make with one or more combination wherein.
Collagem membrane in the described fiber reinforcement compacted zone is by collagen solution or collagen solution composite Nano silver particles, or the compound water miscible medication preparation of collagen solution obtains.Wherein, collagen solution mainly refers to by type i collagen albumen, or fusion has on a small quantity the III collagen protein of (quality that accounts for total collagen protein than content less than 5%) to be dissolved in a kind of natural polymers solution that forms in the organic acid solvent in the type i collagen albumen.The nano silver particles size may be selected to be the nano-Ag particles of 1 ~ 100 nanometer.
Wherein water miscible medicine is selected from one or more the combination in paclitaxel, amycin, streptomycin, cefradine, gentamycin, acetylspiramycin, erythromycin, albomycin, amoxicillin, oxytetracycline, kanamycin, penicillin, metronidazole, danshensu, neomycin, ribostamycin, tetracycline, vancomycin, the azithromycin.Also can be according to using needs to select to use other medicines.
This weaker zone is by being selected from chitosan, fibroin albumen, keratoprotein, the collagen protein one or more for matrix material, and compound a certain amount of hyaluronic acid, chondroitin sulfate, the calcium salt of being selected from, or one or more materials in the BMP somatomedin and forming.Calcium salt includes but not limited to hydroxyapatite, tricalcium phosphate, calcium sulfate etc.
Two-layer compound regeneration membrane of the present invention (Oral Repair film), its preparation method mainly comprises four steps, hereinafter the order of 1 ~ step 4 is described in detail successively set by step.Wherein, the concrete technology of some in step 1 ~ 3 realize applicable to the alternate manner of prior art, and step 4 can be selected to carry out or accept or reject as the operation of post processing, is not as limiting.
Step 1, the preparation of fiber reinforcement compacted zone, what make in the present embodiment is the fibre-reinforced compacted zone of degradable macromolecule, step 1 specifically comprises following technology:
Include but not limited to acetic acid or malonic acid with organic acid solvent, dissolving collagen forms collagen solution, thereby forms the solution that mixes natural polymers; Further compound water soluble drug and/or the nano silver particles that is selected from therapeutic effect optionally, the solution of gained can be carried out earlier being re-introduced in the mould (or other mould of prior art) of design voluntarily after vacuum is deviate from bubble, mould is carried out precooling a period of time, lyophilization again, prepare collagen sponge membrane, standby;
Simultaneously, become net standby degradable macromolecule fibrage; And
At last the collagen sponge membrane for preparing and degradable macromolecule fleece alternately are layering, the superiors and orlop are chosen as collagen sponge membrane, put between two flat boards, use certain mechanical force, compacting a period of time, prepare by the film formed fiber reinforcement compacted zone of degradable macromolecule fleece composite collagen.
In the specific embodiment, organic acid pH=1 ~ 4 in this step 1, described collagen solution, mainly refer to by type i collagen albumen, or fusion has on a small quantity the III collagen protein of (quality that accounts for total collagen protein than content less than 5%) to be dissolved in a kind of natural polymers solution that forms in the organic acid solvent in the type i collagen albumen.Solute mass volume ratio (m/v) concentration range of collagen solution is 0.1 ~ 2%, and viscosity coefficient is 1000 ~ 4000cp.In collagen solution, the concentration of described nanometer silver is 40 ~ 800ppm, and the concentration of water soluble drug is 10
-3~ 20mmol/L.The nano silver particles size may be selected to be the nano-Ag particles of 1 ~ 100 nanometer.
Vacuum when vacuum is deviate from bubble can be 0 ~ 100Pa.Described lyophilization condition can be: freezing 2h under subzero 40 ~ 90 ℃ of ultralow temperature, put into freezer dryer, lyophilization 24h under subzero 50 ~ 60 ℃ of conditions after freezing.
The diameter range of degradable medical macromolecular fibre can be but is not limited to 0.1 ~ 1mm, weaves the weaving method commonly used that the method into the net that interweaves can adopt medical textile.Collagen sponge membrane and degradable macromolecule the fleece alternately number of plies of stack are 3 ~ 15 layers, and compacting is to suppress 4 ~ 24 h under the active force of 5 ~ 10 KN scopes, thereby form thickness at the compacted zone of 0.5 ~ 2mm.Pressing conditions and the number of plies can be adjusted and select according to actual needs.
The mould that indication designs voluntarily, essence comprise a large-area rectangular flat plate, and mould can temperature automatically controlled heating and oven dry, and for example temperature controlling range is 0 ~ 80 ℃; The supporting spreader that is provided with in the described mould, when mould and spreader use together, can disposable preparation large-size uniform film; But spreader is the micropore roller bearing of an inside splendid attire solution, and the solution in the roller bearing slowly flows out from micropore under certain pressure, and constantly rolls back and forth with the roller bearing of automatic control, equably with solution drawout in mould; Solution injects in the roller bearing of spreader by the continuous feed pipe.Other mould and the method for prior art are equally applicable to the present invention, and therefore step of the present invention is not defined as the mould of design voluntarily.
Step 2, the preparation of weaker zone, step 2 specifically comprises following technology:
Include but not limited to acetic acid or malonic acid with organic acid solvent, the dissolving chitosan, or fibroin albumen, or keratoprotein, or in the collagen protein polymer one or more are mixed with solution, and further compound a certain amount of hyaluronic acid also, or the sulfate composite chrondroitin, or compound a certain amount of calcium salt, or in the BMP somatomedin one or several are mixed with into solution;
The solution of gained is injected the mould (mould structure mould the same and prior art is suitable equally) of design voluntarily; And
Then mould is put into freezing a period of time in the ultra cold storage freezer, lyophilization again, thus making the weaker zone collagen sponge, its thickness carries out the thickness adjustment less than 3 millimeters but can be suitable for according to reality.
In the specific embodiment, the m/v concentration of chitosan described in the solution of this step 2 is 0.1 ~ 3%, the m/v concentration of fibroin albumen is 0.2 ~ 5%, the m/v concentration of keratoprotein is 0.1 ~ 8%, the m/v concentration of collagen protein polymer is 0.1 ~ 2%, hyaluronic m/v concentration is 0.05 ~ 1.5%, and the m/v concentration of chondroitin sulfate is 0.05 ~ 0.3%, and the m/v concentration of calcium salt is 0.05 ~ 3%; The m/v concentration of BMP somatomedin is 0.00001 ~ 0.015%, and wherein m/v refers to mass volume ratio.The lyophilization condition can be: freezing 2h under subzero 40 ~ 90 ℃ of ultralow temperature, put into freezer dryer, lyophilization 24h under subzero 50 ~ 60 ℃ of conditions after freezing.
Step 3, the preparation of guiding film, step 3 specifically comprises following technology:
Fibre-reinforced compacted zone is carried out high-temperature cross-linking;
Weaker zone carries out the crosslinked and chemical crosslinking of vacuum high-temperature, then crosslinked weaker zone is cleaned precooling, lyophilization a period of time then; And
Carry out at last compacted zone and weaker zone compound, the preparation two-layer compound guiding film.
In the specific embodiment, in this step 3, high-temperature cross-linking and vacuum high-temperature are crosslinked to be at 80 ~ 130 ℃ of following cross-linking reaction 8 ~ 30h.When carrying out chemical crosslinking, be to soak 8 ~ 24 h in cross-linking agent, described cross-linking agent is selected from one or more in glutaraldehyde, genipin, the carbodiimides, and the m/v concentration of cross-linking agent is 0.1 ~ 2%.Described cleaning is: the sample that carries out after the chemical crosslinking soaks 1 ~ 3h in PBS solution, soak 0.5 ~ 2h in 20 ~ 60% the alcoholic solution again, and then soak 24h in the normal saline, constantly clean, clean 24 h with distilled water at last, constantly change water, remove cross-linking agent residual in the sample, and the low-molecular material in the sample is water-washed away.Other cleaning is suitable equally; Cleaned behind the sample again at subzero 20 ~ 80 ℃ of freezing 2h lyophilization under subzero 40 ~ 60 ℃ of conditions then.
The compound operational approach of compacted zone and weaker zone is the prepared natural polymers solution of one side coating one deck step 1 at compacted zone, put weaker zone, lyophilization then, prepare the guiding regeneration membrane that is made of fibre-reinforced compacted zone and weaker zone, freezing and drying process can be adjusted or selects by concrete needs.
Step 4 is directly taken out the guiding film of preparation from mould, carry out technologies such as cutting, packing and sterilization and prepare the guiding film product.
Be instantiation below, Oral Repair film of the present invention and preparation method thereof is described, but not as the restriction of protection domain of the present invention.
Embodiment 1: strengthen the preparation of compacted zone
(1) get the collagen sample, form natural polymers solution with organic acid solvent according to finite concentration dissolving collagen, organic acid is acetic acid or malonic acid; The PH=1 of solvent ~ 3 wherein, the viscosity of mixed liquid 2300cp of formation, adding concentration is the nanometer silver of 80ppm, fully stirs 12h in room temperature then, obtains the solution that homogeneous mixes, stand-by;
(2) getting the collagen mixed solution of homogeneous, is 0 Pa in vacuum, time of repose 1 ~ 10min; Deviate from the most of bubble in the solution;
(3) collagen and the nanometer silver mixed solution that will deviate from bubble is poured in the homemade polytetrafluoro mould, and drawout is put into freezing 2h under subzero 80 ℃ of conditions to mould then, then at 0 Pa, lyophilization 24 h under subzero 56 ℃ of conditions prepare collagen sponge membrane, and are standby;
(4) adopting the preparation method of general medical textile, is that the degradable macromolecule fibrage of 0.1mm becomes net with diameter, standby;
(5) then the collagen sponge membrane for preparing and degradable macromolecule fleece alternately are layering, the superiors and orlop are collagen sponge membrane, totally 7 layers, put between two polytetrafluoro flat boards, under the active force of 9 KN, suppress 24h, prepare the compacted zone that the degradable medical macromolecular fibre strengthens, thickness is in 0.5 ~ 1mm scope.
Embodiment 2: the preparation of weaker zone
(1) gets the collagen sample, with organic acid solvent dissolving collagen protein polymer formation solution, and add a certain amount of hyaluronic acid and BMP somatomedin; The PH=1 of solvent ~ 3 wherein, the viscosity coefficient 1200cp of collagen solution; Hyaluronic mass fraction is 0.05 ~ 1.5%(m/v); The concentration of BMP somatomedin is 0.00008%(m/v);
(2) the mixed solution that configures according in a certain amount of mould that is cast in homemade polytetrafluoro, mould is put into freezing 2h under subzero 80 ℃ of conditions, then at 0 Pa, lyophilization 24h under subzero 56 ℃ of conditions prepares weaker zone.
Embodiment 3 strengthens the crosslinked and compound of compacted zone and weaker zone
(1) compacted zone for preparing and weaker zone are put into vacuum drying oven respectively, evacuation, vacuum under the state of 0.1 Pa, high-temperature cross-linking 12 ~ 30 h; Hot crosslinked temperature is 100 ~ 130 ℃.
(2) weaker zone behind the high-temperature cross-linking is put into container, add cross-linking agent, the concentration of cross-linking agent is 0.1 ~ 1.5%, and crosslinked 12h is selected from the cross-linking agent such as glutaraldehyde, genipin, carbodiimides, epoxide one or more.
(3) weaker zone of chemical crosslinking is cleaned, condition is: soak 1 ~ 3h in PBS solution, and then soak 0.5 ~ 2h in 20 ~ 60% the alcoholic solution, and then soak 24h in the normal saline, constantly clean, clean 24h with distilled water at last, constantly change water; Remove cross-linking agent residual in the sample, and the lower-molecular substance water in the sample is washed off.Cleaned behind the sample at subzero 20 ~ 80 ℃ of freezing 2h, lyophilization under subzero 40 ~ 60 ℃ of conditions prepares crosslinked weaker zone then again;
(4) at last compacted zone and weaker zone are carried out compoundly, operational approach is that the one side at compacted zone applies the prepared natural polymers solution of one deck example 1, puts weaker zone, lyophilization then, can prepare double-deck guiding regeneration membrane.
Prepared double-layered compound film as stated above, this film can be used for osseous tissue, tissue repair such as dental tissue.It is to be base stock with natural polymer and synthetic high polymer, adopt cast, coating, compacting, lyophilization molding, and through physical crosslinking or the chemical crosslinking modified double-layered compound film that is prepared from, have good biocompatibility and mechanical property, the biodegradable performance, and immunological rejection is lower, simple operation and other advantages.This material is widely used in tissue repair, especially the reparation of osseous tissue and periodontal tissue.
This film has following characteristics: (1) adopts biocompatibility and biodegradable high molecular polymer to prepare guiding film, and tissue reaction is little, can not cause organism immune response and confirmatory reaction; (2) adding of therapeutic effect medicine is arranged, promote the healing effect of wound; (3) fibroreticulate adding improves the mechanical strength of guiding film, and degradation time is controlled; (4) guiding film that increases of the adding of inorganic constituents and BMP somatomedin become bone bioactivity, promote osteoblastic growth.
The experiment proved that the compound guiding film of the present invention preparation has good biological activity, antibiotic property, mechanical strength preferably, degradation rate is adjustable, promotes advantages such as wound healing, degradation in vivo or be 4 ~ 12 months by the time that body absorbs fully.Adopt GB/T 528 to test, the fracture tensile strength under this regeneration membrane hygrometric state is 5 ~ 40 MPa.Adopting national standard test cell toxicity is 0 grade.This MULTILAYER COMPOSITE regeneration membrane is applied to the reparation of the reparation of defective tissue, particularly osseous tissue and dental tissue, has broad application prospects.
Claims (10)
1. a two-layer compound regeneration membrane comprises compacted zone and weaker zone, it is characterized in that: described compacted zone is composited by degradable macromolecule fleece and collagem membrane.
2. two-layer compound regeneration membrane as claimed in claim 1 is characterized in that: be compounded with nano silver particles and/or medicine in the described collagem membrane; Described weaker zone is by being selected from chitosan, fibroin albumen, and keratoprotein, or in the collagen protein one or more form as matrix material.
3. two-layer compound regeneration membrane as claimed in claim 1, it is characterized in that: described compacted zone is that degradable macromolecule fleece and collagem membrane alternately are layering, and the superiors and orlop are collagem membrane, and thickness is 0.5 ~ 2mm; Contain a certain amount of hyaluronic acid that is selected from the described weaker zone, chondroitin sulfate, calcium salt, or one or several formation in the bone morphogenic protein BMP-2 somatomedin.
4. two-layer compound regeneration membrane as claimed in claim 1, it is characterized in that: the fibroreticulate material of described degradable macromolecule is selected from medical grade polydioxanone, polylactic acid, poly (glycolide-lactide), polycaprolactone, the combination of one or more in poly-(3-butyric ester-3-hydroxyl valerate).
5. two-layer compound regeneration membrane as claimed in claim 2 is characterized in that: described medicine is selected from one or more the combination in paclitaxel, amycin, streptomycin, cefradine, gentamycin, acetylspiramycin, erythromycin, albomycin, amoxicillin, oxytetracycline, kanamycin, penicillin, metronidazole, danshensu, neomycin, ribostamycin, tetracycline, vancomycin, the azithromycin.
6. as each described two-layer compound regeneration membrane in the claim 1 ~ 5, its preparation method may further comprise the steps:
Step 1, the preparation of fiber reinforcement compacted zone further comprises following technology:
Form collagen solution with organic acid dissolving collagen, collagen solution is injected in the mould, lyophilization then, preparation collagen sponge membrane;
Become net as enhancement layer with degradable macromolecule fibrage; And
The collagen sponge membrane for preparing and the degradable macromolecule fiber web layer system of laminating is formed compacted zone by the compound degradable medical macromolecular fibre enhancing of degradable macromolecule fleece and collagem membrane;
Step 2, the preparation of weaker zone further comprises following technology:
Be selected from chitosan with the organic acid dissolving, fibroin albumen, keratoprotein, one or more in the collagen protein polymer form solution; And
The solution of gained is injected mould, lyophilization then, preparation weaker zone collagen sponge;
Step 3, compacted zone and weaker zone are compounded to form the two-layer compound regeneration membrane.
7. as the preparation method of two-layer compound regeneration membrane as described in the claim 6, it is characterized in that: in the step 1, described collagen solution is type i collagen albumen, or contains a small amount of III collagen type in the type i collagen albumen and be dissolved in the solution that forms in the organic acid; Further be compounded with medicine and/or nano silver particles in the described collagen solution.
8. as the preparation method of two-layer compound regeneration membrane as described in the claim 7, it is characterized in that: in the step 1, the mass volume ratio concentration range of collagen solution is 0.1 ~ 2%, and viscosity coefficient is 1000 ~ 4000cp; Be 10 in drug concentrations described in the collagen solution
-3~ 20mmol/L, the concentration of nanometer silver is 40 ~ 800ppm; Collagen sponge membrane and degradable macromolecule fiber web layer poststack, the superiors and orlop are collagen sponge membrane, put into the certain thickness compacted zone of compacting formation between the flat board then.
9. as the preparation method of two-layer compound regeneration membrane as described in the claim 6, it is characterized in that: in the step 2, described solution injects the before further compound a certain amount of hyaluronic acid that is selected from of mould, sulfate composite chrondroitin, calcium salt, one or more materials in the BMP somatomedin; The mass volume ratio concentration of chitosan described in the solution is 0.1 ~ 3%, the mass volume ratio concentration of fibroin albumen is 0.2 ~ 5%, the mass volume ratio concentration of keratoprotein is 0.1 ~ 8%, the mass volume ratio concentration of collagen protein polymer is 0.1 ~ 2%, hyaluronic mass volume ratio concentration is 0.05 ~ 1.5%, the mass volume ratio concentration of chondroitin sulfate is 0.05 ~ 0.3%, and the mass volume ratio concentration of calcium salt is 0.05 ~ 3%; The mass volume ratio concentration of BMP somatomedin is 0.00001 ~ 0.015%.
10. as the preparation method of two-layer compound regeneration membrane as described in the claim 6, it is characterized in that: in the described step 3, be with the fiber reinforcement compacted zone carry out high-temperature cross-linking, weaker zone carries out high-temperature cross-linking and chemical crosslinking, then crosslinked weaker zone is cleaned lyophilization; Carry out the compound of compacted zone and weaker zone at last, thereby obtain the two-layer compound regeneration membrane; The compound operational approach of compacted zone and weaker zone is the prepared collagen solution of one side coating one deck step 1 at compacted zone, puts weaker zone, lyophilization then.
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| CN112402703A (en) * | 2020-10-27 | 2021-02-26 | 北京幸福益生高新技术有限公司 | Double-layer porous composite biological membrane containing bioactive mineral material and preparation method thereof |
| CN113069586A (en) * | 2021-04-01 | 2021-07-06 | 浙江理工大学 | Preparation method of double-layer wound dressing containing wax-coated silk fibroin fabric layer and regenerated silk fibroin silver-loaded medicine layer |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1529653A (en) * | 2001-05-16 | 2004-09-15 | �й���ѧԺ���ݻ�ѧ�о��� | Biodegradable and/or biological absorbing fiber product and its use in medical application |
| CN1586637A (en) * | 2004-09-13 | 2005-03-02 | 中国医学科学院生物医学工程研究所 | Double layer composite collagen base guide tissue regeneration film and its preparing method |
-
2012
- 2012-01-09 CN CN201210004501.8A patent/CN103191085B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1529653A (en) * | 2001-05-16 | 2004-09-15 | �й���ѧԺ���ݻ�ѧ�о��� | Biodegradable and/or biological absorbing fiber product and its use in medical application |
| CN1586637A (en) * | 2004-09-13 | 2005-03-02 | 中国医学科学院生物医学工程研究所 | Double layer composite collagen base guide tissue regeneration film and its preparing method |
Non-Patent Citations (1)
| Title |
|---|
| T. VON ARX ET AL.: "Evaluation of a prototype trilayer membrane (PTLM) for lateral ridge augmentation: an experimental study in the canine mandible", 《 INT. J. ORAL MAXILLOFAC. SURG.》, vol. 31, 31 December 2002 (2002-12-31), pages 190 - 199 * |
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