CN1164655C - Preparation method of multi-layer high-molecular material - Google Patents
Preparation method of multi-layer high-molecular material Download PDFInfo
- Publication number
- CN1164655C CN1164655C CNB011452978A CN01145297A CN1164655C CN 1164655 C CN1164655 C CN 1164655C CN B011452978 A CNB011452978 A CN B011452978A CN 01145297 A CN01145297 A CN 01145297A CN 1164655 C CN1164655 C CN 1164655C
- Authority
- CN
- China
- Prior art keywords
- layer high
- preparation
- molecular material
- molecular
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Images
Landscapes
- Materials For Medical Uses (AREA)
Abstract
The present invention relates to a method for preparing multilayer macromolecule materials, which comprises the steps that macromolecule materials and water-soluble materials are mixed in a required proportion to obtain a mixture; the mixture is orderly filled into a mould; the surfaces of the macromolecule materials in the mixture are dissolved, and are mutually conglutinated; water enters the inside of the macromolecule materials in the mould, macromolecules are solidified, and the water-soluble materials in the mixture can be washed. The mixed weight proportion of granules of the macromolecule materials and soluble granules with different granule diameters is changed according to the present invention, and raw material granules are orderly filled into the mould according to different requirements to form required layers. A double-layer or multilayer macromolecule material which comprises different hole diameters, different porosity factors or different materials is prepared by a continuous preparation process to be corresponding to different requirements of tissue engineering.
Description
Technical field
The present invention relates to a kind of preparation method of multi-layer high-molecular material, particularly relate to a kind of preparation method who is used for the macromolecular material of biotechnology.
Background technology
In recent years, along with the progress of biotechnology, living doctor's material and histiocytic culture technique mutually combine, develop gradually this new research field of organizational project (tissue engineering).And a quite important gordian technique is arranged in the technology of organizational project, be the porous substrate of development decomposability, utilize its three-dimensional space framework to attach by histocyte and growth thereon, after histocyte gradually grows up, replacement will be degraded and be absorbed to this porous material gradually, and the composite base material of final cell of implanting and material can replace original rejected region and become the some of human body.Owing to will allow cell grow in the material, therefore the porous material of being developed need possess following characteristic:
1. can absorb decomposability
2. high porosity
3. suitable aperture
4. three-dimensional cellular structure
5. prepared hole is required to be the pore texture that is interconnected
Aspect the material selection of absorbability, the macromolecular material with Biodegradable (Biodegradable) is paid attention to by the investigator most at present, and this type of polymer is as poly-glycollide acid (Polyglycolic acid; PGA), polylactide acid (Polylactic acid; PLA), poly-glycollide acid is total to rac-Lactide acid [Poly (glycolide-co-Lactide) acid; PLGA]], polycaprolactone (Polycaprolactone), polydioxanone (Polydioxanone) or poe materials such as (Polyorthoester), these co-polymers can be decomposed into the small molecules segment in vivo, these products will excrete along with the intravital new one-tenth metabolic process of people, so its split product will can not residue in the body.In recent years along with the development of tissue engineering technique, existing several processing procedures can prepare the high-molecular porous property base material of Biodegradable, yet prepare the multi-layer porous property material that multi-level different apertures, different porosities or differing materials are formed, present correlation technique all can't prepare under same successive processing procedure to be finished.
Present tissue engineering technique need be chosen the tissue of patient or contributor's sub-fraction health, after external a large amount of cultivations, implant the porous substrate of a decomposability, utilize its three-dimensional space framework to attach by histocyte and growth thereon, after histocyte gradually grows up, replant go back to the position of the required repairing of patient.The arrangement and the form of the tissue that the framework decision of use therein three-dimensional space porous substrate will form, the preparation method of present relevant porous substrate can only prepare the porous substrate that single pore texture or single-material become to be grouped into, yet tissue is continuity and multi-level structure, its level comprises density of matrix between different tissues and the multilayered structure that differing materials constituted, and therefore develops adjustable different porous gap architectures and combination of materials is the gordian technique of present required breakthrough.
According to the retrieval and the analysis of patent, can conclude the high-molecular porous property of present preparation material has following method:
1. solution casting (solution casting)
2. solvent casting salt is washed method (solvent-casting particulate leaching)
3. colloid casting (gel casting)
4. saturated gas foaming (gas saturation)
5. phase separation method (phase separation)
6. fibre cementing method (bonded fiber)
7. particle sintering process (particle sintering).
Above-mentioned method can be prepared the base material of different porosities or pore size according to its processing procedure characteristic, yet it is not mentioned by at present relevant patent processing procedure to prepare multi-level different porosities, pore size and differing materials compound base material continuously.Though in U.S. Pat Pat.5514378, mention and to utilize solvent casting salt to wash the porous substrate film of method preparation; remove the three-dimensional space base material of overlapping preparation different levels with the film of two-dimensional space; yet this method is subject to salt and macromolecular solution density at a distance of too big skewness; the salt particle may be coated fully and problems such as residual organic solvent are understood in base material inside; prepared base material thickness is limited; only can prepare the high-molecular porous crack film of about 2000 μ m thickness; preparing thicker or three-dimensional base material then needs to carry out in the mode of piling up; though the thin layer that multi-level base material can borrow interpolation different apertures salt particle or salt adding proportion to prepare different apertures and porosity arranges to pile up the required multi-level pore texture three-dimensional space base material of composition more according to need.Yet the shortcoming of this method is that the single layer of substrate material thickness that can prepare is limited, its processing procedure middle level mainly links together it by solvent with the binding of layer, the hole of different layers interface portion will be dissolved by solvent and shut, and this mode is discontinuous preparation method, need to pile up complex procedures and do not conform with cost benefit manually to process.Though phase separation method can utilize agglomerative ice crystal form to control the form of its hole,, and can't directly apply to the multi-level porous substrate of preparation at present in the technology prematurities still such as form, granular size, uniformity coefficient and arrangement of controlling ice crystal.
Wash the processing procedure of method according to solvent casting salt, can find that it prepares the main difficulty of three-dimensional base material and is to make polymer to separate out and the aqueous solution during the salt washing can't import and go deep in the material.Therefore, previous patent is intended separating out and importing a pressure during salt washing at polymer, utilizes pressure that water lotion is imported and gos deep in the material, thereby make inner polymer separate out and the salt particle is washed out.Macromolecular material is all in the macromolecular solution of liquid phase yet depend pressure alone and rinsing solution is imported, so in this patented method, will be insoluble to and go in the organic solvent to mix with the salt particle again.
Summary of the invention
In view of this, the present invention proposes the multi-level porous material that a novel method can prepare different apertures, different porosities or differing materials composition fast.This method is the manufacturing method thereof that continues the patent of before filing an application (TaiWan, China patent application case No.90120067, the date of application is 89.08.16).The method for preparing multi-layer high-molecular material of the present invention is that high molecular particle is mixed in solid-state mode mutually with the salt particle; inserting one can import in the mould of liquid and pressure; importing organic solvent makes it by polymeric particles and salt blend of granules whose; and then the also softening polymeric particles of dissolving polymeric particles is surperficial and it is bondd each other; apply a negative pressure and take out unnecessary solvent this moment; and make between the polymeric particles of surface dissolution and particle bonding each other; import the aqueous solution this moment again; make it to make it separate out and solidify by surface dissolution remollescent polymeric particles; because polymeric particles is to mix in solid-state mode with the salt particle; there is a large amount of spaces that the aqueous solution is imported between its particle and gos deep in the material; and water lotion dissolved salts particle simultaneously produces more hole; so a large amount of water lotions is imported and by in the material by negative pressure; and the hole of material internal after the dissolving of salt particle; space between the solidified polymer and water lotion will communicate with each other its inside holes and become the three-D space structure that possesses high porosity by formed pipeline.
According to above principle, the present invention mixes the soluble material particle of different-grain diameter of Different Weight ratio or the particle that doctor's ceramic powder is given birth in blending (hydroxyapatite (hydroxyapatite for example in advance with macromolecule material particle; HAP)), according to different needs feed particles is inserted bilayer or the multi-layer high-molecular material that forms needed multi-level (including different apertures, different porosities or differing materials) composition in the mould in regular turn, with the different demands of corresponding organizational project.
The object of the present invention is to provide a kind of method that can prepare the layer high molecule material of multi-level different aperture, different porosities or differing materials composition fast.
Above-mentioned purpose of the present invention is achieved in that a kind of preparation method of multi-layer high-molecular material, and it may further comprise the steps:
A. obtain a mixture with required mixed macromolecular material and water-soluble material;
B. described mixture is inserted in the mould in regular turn;
C. make the polymer surface dissolving in the described mixture also adhered to one another; And
D. make water enter described macromolecular material inside in the described mould, make polymeric hardener and wash out the water-soluble material of described mixture inside.
The preparation method of multi-layer high-molecular material of the present invention, wherein step a mixes polymer composite and water-soluble material with solid-state form.
The preparation method of multi-layer high-molecular material of the present invention, wherein the required ratio of differing materials is that material, aperture and porosity according to prepared multi-layer high-molecular material decided among the step a.
The preparation method of multi-layer high-molecular material of the present invention, the wherein thickness of the different levels of the formed multi-layer high-molecular material of amount may command of the macromolecular material mixing water-soluble material of inserting among the step b.
The preparation method of multi-layer high-molecular material of the present invention, wherein said macromolecular material is that more than one are selected and freely gather glycollide acid, polylactide acid, the rac-Lactide acid altogether of poly-glycollide, polyanhydride, polycaprolactone, the group that polydioxanone and poe are formed.
The preparation method of multi-layer high-molecular material of the present invention, wherein said macromolecular material also comprises selects free hydroxyl phosphatic rock, tricalcium phosphate, tetra-sodium dicalcium, tetracalcium phosphate, octocalcium phosphate, the group that collagen protein and gelatin are formed.
The preparation method of multi-layer high-molecular material of the present invention, wherein said macromolecular material is a particulate state or fibrous.
The preparation method of multi-layer high-molecular material of the present invention, the size of wherein said macromolecular material is between 50 to 1000 μ m.
The preparation method of multi-layer high-molecular material of the present invention, wherein said water-soluble material is to be selected from by sodium-chlor, Repone K, Potassium Bromide, calcium chloride, magnesium chloride, polyoxyethylene glycol, gelatin, the group that glucose and sucrose are formed.
The preparation method of multi-layer high-molecular material of the present invention, wherein said step c utilize solvent to make macromolecule surface dissolving and bonding mutually.
The preparation method of multi-layer high-molecular material of the present invention, wherein this solvent is to be selected from by 1,4-diox, acetone, trichloromethane, methylene dichloride, tetrahydrofuran (THF), N, dinethylformamide, ethyl acetate, hexafluoroisopropanol, the group that Perfluoroacetone and sesquialter hydrate are formed.
The preparation method of multi-layer high-molecular material of the present invention, but wherein said mould is the mould of filtration under diminished pressure.
The preparation method of multi-layer high-molecular material of the present invention, wherein this preparation method carries out in the device of the decompression extraction equipment that possesses mould and may command pressure.
The preparation method of multi-layer high-molecular material of the present invention, the mode of inserting of wherein said step b is to carry out with stack manner.
In order to reach the present invention, the preparation method of multi-layer high-molecular material of the present invention, its step comprises: a. obtains a mixture with required mixed macromolecular material and water-soluble material; B. this mixture is inserted in the mould in regular turn; C. make the polymer surface dissolving in this mixture also adhered to one another; D. make water enter this macromolecular material inside in this mould, make polymeric hardener and wash out the water-soluble material of this mixture inside.
The step a of aforesaid method mixes polymer composite and water-soluble material with solid-state form, and the required ratio of the differing materials of above-mentioned indication is that material, aperture and porosity according to prepared multi-layer high-molecular material decided.Indivedual level thickness of the different levels of the formed multi-layer high-molecular material of amount may command of the macromolecular material mixing water-soluble material of inserting of step b, there is no particular restriction as for the mode of inserting of described material, can pile up or the concentric(al) circles mode is carried out; Step (c) is to utilize solvent to make macromolecule surface dissolving and bonding mutually.
Be applicable to that macromolecular material of the present invention is that more than one select autohemagglutination glycollide acid (polyglycolic acid; PGA), polylactide acid (polylactic acid; PLA), poly-glycollide is total to rac-Lactide acid (poly (glycolide-co-Lactide) acid; PLGA), polyanhydride (polyanhydrides), the group that polycaprolactone (polycaprolactone) polydioxanone (polydioxanone) and poe (polyorthoester) are formed, in addition, also macromolecular material can be mixed other material, as hydroxyapatite (HAP), tricalcium phosphate (tricalcium phosphate), tetra-sodium dicalcium (dicalcium pyrophosphate), tetracalcium phosphate (tetracalcium phosphate), octocalcium phosphate inorganic materials such as (octacalciumphosphate), or collagen protein (collagen) and gelatin biological materials such as (gelatin).There is no particular restriction for the shape of this macromolecular material, is preferably particulate state or fibrous; Size as for this macromolecular material is preferably between 50 to 1000 μ m.
Be applicable to that water-soluble material of the present invention is selected from by sodium-chlor (NaCl), Repone K (KCl), Potassium Bromide (KBr), calcium chloride (CaCl
2), magnesium chloride (MgCl
2), polyoxyethylene glycol [Poly (ethyleneglycol)], gelatin (gelatin), the group that glucose and sucrose are formed.
Be applicable to that solvent of the present invention is selected from by 1,4-diox (1,4-dioxane), acetone (acetone), trichloromethane (chloroform), methylene dichloride (dichloromethane), tetrahydrofuran (THF) (tetrahydrofuran), N, dinethylformamide (N, N-dimethylformamide), ethyl acetate (ethylacetate), hexafluoroisopropanol (hexafluoroisopropanol), the group that Perfluoroacetone (hexafluoroacetone) and sesquialter hydrate (sesquihydrate) are formed.
But be applicable to the mould of device of the present invention, except mould, also can comprise the decompression extraction equipment of control pressure for filtration under diminished pressure.
According to the present invention, can use a successive processing procedure to prepare the multi-layer high-molecular material that multi-level different apertures, different porosities or differing materials are formed, and the multi-layer high-molecular material that makes has can absorb decomposability, and can form three-dimensional cellular structure according to required material behavior, porosity and aperture, in addition, the hole of prepared multi-layer high-molecular material is the pore texture that is interconnected, and meets the important document that is applied to biotechnology fully.
In order to allow above-mentioned purpose of the present invention, feature and advantage become apparent,, and in conjunction with the accompanying drawings, elaborate below especially exemplified by going out preferred embodiment.
Description of drawings
Fig. 1 is the device synoptic diagram of preparation multi-layer high-molecular material of the present invention;
Fig. 2 a is the structure of piling up the multi-layer high-molecular material that forms with the two-layer different apertures that scanning electron-microscopic observation embodiment 1A makes;
Fig. 2 b is the structure at the multi-layer high-molecular material interface that makes with scanning electron-microscopic observation embodiment 1A;
Fig. 3 is the structure of the multi-layer high-molecular material that makes with scanning electron-microscopic observation embodiment 1B;
Fig. 4 is the structure of the multi-layer high-molecular material that makes with scanning electron-microscopic observation embodiment 1C;
Fig. 5 is the structure of the multi-layer high-molecular material that makes with scanning electron-microscopic observation embodiment 1D;
Fig. 6 is the structure of the cylindrical porous of the concentric(al) circles crack macromolecular material that makes with scanning electron-microscopic observation embodiment 1E;
Fig. 7 is the structure with scanning electron-microscopic observation embodiment 2 prepared multi-level many porositys macromolecular materials;
Fig. 8 is the structure with scanning electron-microscopic observation embodiment 3 prepared multi-layer high-molecular materials.
Embodiment
The multi-layer high-molecular material that embodiment 1-forms in different apertures
The selected material of present embodiment is:
A. macromolecular material: the poly-glycollide for preparing in the ring-opening polymerization mode is rac-Lactide acid (PLGA) polymer altogether, and its molecular weight is determined as 200,000 according to gel osmoticing chromatogram analysis method (gel permeationchromatography).Above-mentioned poly-glycollide is total to rac-Lactide acid (PLGA) pulverizes in pulverizer, the particle of pulverizing can obtain the material granule of particle diameter between 177-250 μ m after sieving by 60-80 hole purpose screen cloth.
B. water-soluble material: with the sodium chloride particle of screen cloth screening different-grain diameter, scope is between 50 μ m～1000 μ m.
C. solvent: 1, the 4-diox (1,4-dioxane)
At first, with identical weight ratio with the mode uniform mixing of above-mentioned each material granule to stir, mixing the back pours in as shown in Figure 1 the mould 10 and compacting according to the different-grain diameter size in regular turn, pour into organic solvent 20 in the composite grain 30 and with its infiltration this moment, then open extraction valve 40, produce a negative pressure with vacuum pump (vacuum pump) 50 and take out unnecessary solvent downwards in container 60, and the composite material granular that has dissolved on the surface is bondd mutually.
Then, above strainer, pour a poly-glycollide into and be total to the insoluble solvent (non-solvent) of rac-Lactide acid the rac-Lactide granulates curing altogether of partly soluble poly-glycollide, pour a large amount of deionized waters thereafter, opening extraction valve simultaneously bleeds, this moment, a large amount of water will be by in the material, separate out and further solidify and gather the glycollide polymer of rac-Lactide acid material granule surface adhesion altogether, simultaneously that it is inner sodium chloride particle is washed out.
Then, take out the multilayer material base material after solidifying in the inherent filtration device, place the large beaker that deionized water is housed, changed water once at room temperature per six hours, with the mode soaking and water washing that stirs a day, solvent and salt grain that inside is residual wash out, and place 50 ℃ vacuum drying oven heat drying one day again, can obtain required multi-layer high-molecular material base material.
Indivedual levels of the multi-layer high-molecular material that present embodiment is prepared are separated into little test piece with blade with it, the pore size method for measurement of indivedual levels is according to the method test of ASTM D-3576-94, and the measurement rule of porosity is measured the length of test piece and calculated its volume.Accurately measure test piece weight with micro-Libra again, with the weight of measurement and the density p of volume calculation test piece
*, be total to rac-Lactide acid (PLGA) theoretical density ρ: 1.28g/cm according to 85/15 poly-glycollide again
2Calculate porosity %=1-(ρ
*/ ρ).The material microstructure is then with scanning electron-microscopic observation, and actuating current is 40mA.
In order to show that method of the present invention can form various multi-layer high-molecular material according to required pore size, porosity etc., following examples 1A～1E makes multi-layer high-molecular material with above-mentioned materials and method, yet the order that level piles up is used with method and each material granule and then is not quite similar, and division is as follows.
Embodiment 1A: the multi-layer high-molecular material in two-layer different apertures
Use the sodium chloride particle of two kinds of granular size scopes (particle diameter 177-250 μ m and 53-88 μ m) to mix respectively to pile up mutually behind the PLGA macromolecular material to form, wherein the weight ratio of PLGA/ sodium-chlor is all 10/90.
Fig. 2 a is the structure of the porous crack polymer base material that piles up with the two-layer different apertures (one deck PLGA/ sodium-chlor (particle diameter 177-250 μ m)/one deck PLGA/ sodium-chlor (particle diameter 53-88 μ m)) that scanning electron-microscopic observation present embodiment 1A makes.Can find out that by Fig. 2 a prepared porous crack polymer base material presents two levels, its pore size distribution is respectively 209 ± 36 μ m and 69 ± 26 μ m, this two-layer hole size distribution conforms to the sodium-chlor particle diameter that is added, therefore the hole aperture of indivedual levels can be complied with the solubility salt that is added and regulated and control, and the thickness of each level also can be regulated and control according to the addition that adds the PLGA/ sodium chloride particle.
Fig. 2 b is the structure at the polymer base material interface, porous crack that makes with the scanning electron-microscopic observation present embodiment, the porous crack substrate interface that can find out these two-layer different apertures is quite clearly demarcated, there is no disrumpent feelings or discontinuous combining between interface and interface, and the different hole of base material at the joint interface in this two-layer aperture also is the pore texture that links intercommunication mutually.
Embodiment 1B: the sandwich shape multi-layer high-molecular material in three layers of different aperture
Use the sodium chloride particle of two kinds of granular size scopes (particle diameter 1 77-250 μ m, 53-88 μ m and 177-250 μ m) to mix respectively to pile up mutually behind the PLGA macromolecular material to form, wherein the weight ratio of PLGA/ sodium-chlor is all 10/90.
Fig. 3 is the structure of the porous crack polymer base material (one deck PLGA/ sodium-chlor (particle diameter 177-250 μ m)/one deck PLGA/ sodium-chlor (particle diameter 53-88 μ m)/one deck PLGA/ sodium-chlor (particle diameter 177-250 μ m)) that makes with scanning electron-microscopic observation present embodiment 1B.The multi-layer high-molecular material that present embodiment 1B makes is the porous crack base material that one deck small-bore, one deck wide aperture adds the three layers of sandwich shape in different apertures in one deck wide aperture again.
Embodiment 1C: the sandwich shape multi-layer high-molecular material in three layers of different aperture
Use the sodium chloride particle of two kinds of granular size scopes (particle diameter 53-88 μ m, 177-250 μ m and 53-88 μ m) to mix respectively to pile up mutually behind the PLGA macromolecular material to form, wherein the weight ratio of PLGA/ sodium-chlor is all 10/90.
Fig. 4 is the structure of the porous crack polymer base material (one deck PLGA/ sodium-chlor (particle diameter 53-88 μ m)/one deck PLGA/ sodium-chlor (particle diameter 177-250 μ m)/one deck PLGA/ sodium-chlor (particle diameter 53-88 μ m)) that makes with scanning electron-microscopic observation present embodiment 1C.Can make the porous crack base material that one deck wide aperture, one deck small-bore adds the three layers of sandwich shape in different apertures in one deck small-bore again by can be observed among the figure according to present embodiment 1C.
Embodiment 1D: the multi-layer high-molecular material in three layers of different aperture
Use three kinds of granular size scope (595-841 μ m; 177-250 μ m; 53-88 μ m) sodium chloride particle mixes respectively to pile up mutually behind the PLGA macromolecular material and forms, wherein the weight ratio of PLGA/ sodium-chlor is all 10/90, with the structure of scanning electron-microscopic observation as shown in Figure 5, the pore size distribution of the multi-layer high-molecular material that makes is 653 ± 43 μ m; 215 ± 187 μ m; 59 ± 23 μ m conform to above-mentioned sodium chloride particle size.
Embodiment 1E: the multi-layer high-molecular material in the different apertures of concentric(al) circles
Use the sodium chloride particle of two kinds of granular size scopes (particle diameter 177-250 μ m and 53-88 μ m) mix respectively behind the PLGA macromolecular material with the concentric(al) circles mode with particle bigger be positioned over mold center, peripheral then place the less sodium chloride particle of particle, wherein the weight ratio of PLGA/ sodium-chlor is all 10/90.
Fig. 6 is the structure of the cylindrical porous of the concentric(al) circles crack polymer base material (centre portions is PLGA/ sodium-chlor (particle diameter 177-250 μ m)/peripheral portion PLGA/ sodium-chlor (particle diameter 53-88 μ m)) that makes with scanning electron-microscopic observation present embodiment 1E, the size that is limited to picture, Fig. 6 is the multi-layer high-molecular material that presents 1/4 concentric circles, the upper right corner is concentrically ringed centre portions, its aperture conforms to above-mentioned sodium chloride particle size greater than peripheral portion.Can find out that thus processing procedure of the present invention also can prepare inside and outside the individual layer different apertures as the multilayered structure of skeletal bones tissue except stack manner.
The multi-layer high-molecular material that embodiment 2-different aperture degree is formed
The selected material of present embodiment is:
A. macromolecular material: with the PLGA polymer that the ring-opening polymerization mode prepares, its molecular weight is determined as 200,000 according to the gel osmoticing chromatogram analysis method.Earlier PLGA is pulverized in pulverizer, the particle of pulverizing can obtain the material granule of particle diameter at 177-250 μ m after sieving by 60-80 hole purpose screen cloth;
B. the material of water-soluble: with the sodium chloride particle of screen cloth screening different-grain diameter, scope is between 50 μ m～1000 μ m;
C. solvent: the 1-4 diox (1,4-dioxane);
In order to make the multi-layer high-molecular material with different aperture degree, present embodiment uses the mode uniform mixing of sodium chloride particle to stir of identical macromolecular material and Different Weight ratio.Mix the back and pour compacting in the mould shown in Figure 1 in regular turn into according to different sodium-chlor interpolation weight ratios, this moment is with organic solvent 1, the 4-diox is poured in the composite grain and with its infiltration, then open extraction valve and produce a negative pressure and take out unnecessary solvent downwards, and the composite material granular that has dissolved on the surface is bondd mutually.(present embodiment is to carry out with the device identical with embodiment 1, and each assembly label is also identical with embodiment 1, therefore will not give unnecessary details.)
Then, after the insoluble solvent of pouring a PLGA above the strainer into (non-solvent) is solidified partly soluble PLGA particle, pour a large amount of deionized waters into, opening extraction valve simultaneously bleeds, this moment, a large amount of water passed through in the material, separate out and further solidify the polymer of PLGA material granule surface adhesion, simultaneously that it is inner sodium chloride particle is washed out.Take out the multilayer material base material after solidifying in the inherent filtration device, place the large beaker that deionized water is housed, changed water once at room temperature per six hours, with the mode soaking and water washing that stirs a day, solvent and salt grain that inside is residual wash out, place 50 ℃ vacuum drying oven heat drying one day again, can obtain required multi-layer high-molecular material base material.
Indivedual levels according to the prepared multi-layer high-molecular material of the foregoing description 2 are separated into little test piece with blade, the pore size measuring method of indivedual levels is according to the method test of ASTM D-3576-94, and the length of the measurement rule of porosity measurement test piece calculates its volume.Accurately measure test piece weight with micro-Libra again, with the weight of measurement and the density p of volume calculation test piece
*, again according to 85/15PLGA theoretical density ρ: 1.28g/cm
2Reckoning mushy material porosity %=1-(ρ */ρ).The material microstructure is then with scanning electron-microscopic observation, and actuating current is 40mA.
Embodiment 1 is the multi-level mushy material in the different apertures of the identical porosity of preparation; embodiment 2 then mixes same particle size (the 177-250 μ m) sodium chloride particle of different amounts with the PLGA particle; insert in regular turn in the mould respectively, prepare the multi-level mushy material of different aperture degree.
Fig. 7 is that the PLGA/ sodium-chlor blending ratio with scanning electron-microscopic observation embodiment 2 is the structure of 10/90 and 30/70 multi-layer high-molecular base material.By finding out on one side comparatively loose (porosity is 89.5 ± 2.3%) among the figure, multi-level mushy macromolecular material of the different aperture degree of densification (porosity is 68.3 ± 3.4%) then on one side.Therefore this two-layer porosity is directly proportional with the sodium-chlor amount of being added, and the porosity of the indivedual levels amount that can comply with the solubility salt that is added is regulated and control, and the thickness of each level also can be regulated and control according to the addition that adds the PLGA/ sodium chloride particle.The porous crack substrate interface of this two-layer different aperture degree does not have broken section or discontinuous combination yet, and these two layers of holes also are the pore texture that links intercommunication mutually.
The multi-layer high-molecular material that embodiment 3-differing materials is formed
Present embodiment 3 selected materials are:
A. macromolecular material: the PLGA polymer for preparing in the ring-opening polymerization mode, and available from the hydroxyapatite (hydroxyapatite of Merck company reagent chemicals; HAP), wherein the PLGA molecular weight is determined as 200,000 according to the gel osmoticing chromatogram analysis method.The preparation of the composite particles of PLGA/HAP be with PLGA and HAP with Different Weight per-cent in mixing roll, be heated to 110 ℃ mixed after, PLGA and PLGA/HAP bulk material are pulverized in pulverizer earlier, after the particle of pulverizing sieves by 60-80 hole purpose screen cloth, can obtain pure PLGA and the PLGA/HAP composite material granular of particle diameter at 177-250 μ m;
B. the material of water-soluble: the sodium chloride particle of different-grain diameter, scope is between 50 μ m～1000 μ m;
C. solvent: the 1-4 diox (1,4-dioxane);
With PLGA and sodium chloride particle (177-250 μ m) the mode uniform mixing to stir of PLGA/HAP composite material granular according to identical weight ratio (10/90) and same particle size.Then, in order pour in shown in Figure 1 mould and compacting after with the mixed chlorinated sodium particle of solid-state mode mixed PLGA and PLGA/HAP composite material granular, this moment is with organic solvent 1, the 4-diox is poured in the composite grain and with its infiltration, open extraction valve then and produce a negative pressure and take out unnecessary solvent downwards, and the composite material granular that has dissolved on the surface is bondd mutually.(present embodiment is to carry out with the device identical with embodiment 1, and each assembly label is also identical with embodiment 1, therefore will not give unnecessary details.)
Then, the insoluble solvent (non-solvent) of pouring a PLGA above strainer into is solidified partly soluble PLGA particle, pour a large amount of deionized waters thereafter, opening extraction valve simultaneously bleeds, this moment, a large amount of water will be by in the material, separate out and further solidify the polymer of PLGA material granule surface adhesion, simultaneously that it is inner sodium chloride particle is washed out.Take out the multilayer material base material after solidifying in the inherent filtration device, place the large beaker that deionized water is housed, changed water once at room temperature per six hours, with the mode soaking and water washing that stirs a day, solvent and salt grain that inside is residual wash out, place 50 ℃ vacuum drying oven heat drying one day again, can obtain required multi-level porous crack base material.
Indivedual levels according to the prepared multi-layer high-molecular material of the foregoing description 3 are separated into little test piece with blade, the pore size measuring method of indivedual levels is according to the method test of ASTM D-3576-94, and the measurement rule of porosity according to Hsuetal. in J.Biomed.Mater.Res.1997:35 (1): the porous crack matrix material porosity method of testing test described in the 107-116.The material microstructure is then with scanning electron-microscopic observation, and actuating current is 40mA.
Fig. 8 is with mixed chlorinated sodium particle of PLGA particle (particle diameter 177-250 μ m) and the mixed chlorinated sodium particle of PLGA/HAP (particle diameter 177-250 μ m) with scanning electron-microscopic observation; blending ratio is the microstructure that the multi-level differing materials of weight ratio 10/90 is formed porous substrate; by the interface that can find out the porous crack base material that this two-layer differing materials is formed among the figure; PLGA/HAP the hole here is because of adding ceramic powder; its structure is comparatively loosened and is contained more trickle hole; yet the porosity of PLGA is through being measured as 88.3 ± 1.9%; material is that the porosity of PLGA/HAP is 90.2 ± 4.1%, and this two-layer thickness also can be regulated and control according to the addition that adds powder.This two-layer different aperture degree there is no too big-difference, and the aperture is no significant difference also, does not also have broken section or discontinuous the combination between interface and interface, and the different hole of base material at the joint interface of this two-layer material also be the pore texture of binding intercommunication mutually.
Though the present invention discloses as above with preferred embodiment; right its is not in order to limiting the present invention, anyly has the knack of this skill person, without departing from the spirit and scope of the present invention; when can doing a little change and retouching, so protection scope of the present invention is as the criterion when looking the claim scope person of defining.
Claims (12)
1. the preparation method of a multi-layer high-molecular material, it may further comprise the steps:
A. obtain a mixture with required mixed macromolecular material and water-soluble material, its described water-soluble material is to be selected from the group that is made up of sodium-chlor, Repone K, Potassium Bromide, calcium chloride, magnesium chloride, polyoxyethylene glycol, gelatin, glucose and sucrose;
B. described mixture is inserted in the mould in regular turn;
C. make polymer surface dissolving in the described mixture and adhered to one another, this step is to utilize solvent to make the macromolecule surface dissolving and bonding mutually; And
D. make water enter described macromolecular material inside in the described mould, make polymeric hardener and wash out the water-soluble material of described mixture inside.
2. the preparation method of multi-layer high-molecular material as claimed in claim 1 is characterized in that, step a mixes macromolecular material and water-soluble material with solid-state form.
3. the preparation method of multi-layer high-molecular material as claimed in claim 1 is characterized in that, the required ratio of differing materials is that material, aperture and porosity according to prepared multi-layer high-molecular material decided among the step a.
4. the preparation method of multi-layer high-molecular material as claimed in claim 1 is characterized in that, inserts the thickness of different levels of the formed multi-layer high-molecular material of amount may command of macromolecular material mixing water-soluble material among the step b.
5. the preparation method of multi-layer high-molecular material as claimed in claim 1, it is characterized in that described macromolecular material is that a kind of being selected from by poly-glycollide, polylactide, poly-glycollide is total to the group that rac-Lactide, polyanhydride, polycaprolactone, polydioxanone and poe are formed.
6. the preparation method of multi-layer high-molecular material as claimed in claim 5, it is characterized in that described macromolecular material also comprises selects the group that free hydroxyl phosphatic rock, tricalcium phosphate, tetra-sodium dicalcium, tetracalcium phosphate, octocalcium phosphate, collagen protein and gelatin are formed.
7. the preparation method of multi-layer high-molecular material as claimed in claim 5 is characterized in that, described macromolecular material is a particulate state or fibrous.
8. the preparation method of multi-layer high-molecular material as claimed in claim 5 is characterized in that, the size of described macromolecular material is between 50 to 1000 μ m.
9. the preparation method of multi-layer high-molecular material as claimed in claim 1, it is characterized in that, this solvent is to be selected from by 1,4-diox, acetone, trichloromethane, methylene dichloride, tetrahydrofuran (THF), N, the group that dinethylformamide, ethyl acetate, hexafluoroisopropanol, Perfluoroacetone and sesquialter hydrate are formed.
10. the preparation method of multi-layer high-molecular material as claimed in claim 1 is characterized in that, but described mould is the mould of filtration under diminished pressure.
11. the preparation method of multi-layer high-molecular material as claimed in claim 1 is characterized in that, this preparation method carries out in the device of the decompression extraction equipment that possesses mould and may command pressure.
12. the preparation method of multi-layer high-molecular material as claimed in claim 1 is characterized in that, the mode of inserting of described step b is to carry out with stack manner.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011452978A CN1164655C (en) | 2001-12-31 | 2001-12-31 | Preparation method of multi-layer high-molecular material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011452978A CN1164655C (en) | 2001-12-31 | 2001-12-31 | Preparation method of multi-layer high-molecular material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1429857A CN1429857A (en) | 2003-07-16 |
| CN1164655C true CN1164655C (en) | 2004-09-01 |
Family
ID=4678121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB011452978A Expired - Lifetime CN1164655C (en) | 2001-12-31 | 2001-12-31 | Preparation method of multi-layer high-molecular material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1164655C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103788390A (en) * | 2014-01-22 | 2014-05-14 | 南京理工大学 | Method for fusing large massive thermoplastic polymer composite material with solvents |
| US12097304B2 (en) * | 2017-05-10 | 2024-09-24 | Board Of Trustees Of The University Of Arkansas | Biocompatible structure for tissue regeneration and methods of making and using same |
| CN108221079A (en) * | 2017-12-20 | 2018-06-29 | 东华大学 | Nanometer hydroxyapatite polycaprolactone nanocrystal composite fibre and preparation method thereof |
-
2001
- 2001-12-31 CN CNB011452978A patent/CN1164655C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CN1429857A (en) | 2003-07-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Babaie et al. | Fabrication aspects of porous biomaterials in orthopedic applications: A review | |
| Yeo et al. | Promoting bone regeneration by 3D-printed poly (glycolic acid)/hydroxyapatite composite scaffolds | |
| US6824716B2 (en) | Process for producing porous polymer materials | |
| Zhao et al. | Preparation of bioactive porous HA/PCL composite scaffolds | |
| KR101031121B1 (en) | Artificial bone and the method of preparing the same | |
| CN105330285B (en) | A kind of 3D printing ZrO2Toughening bioactive ceramics powder body material and its preparation and application | |
| CN100540071C (en) | Medical reinforced porous biological ceramic and preparation method thereof | |
| Shi et al. | A novel hydrophilic poly (lactide‐co‐glycolide)/lecithin hybrid microspheres sintered scaffold for bone repair | |
| Baier et al. | Shape fidelity, mechanical and biological performance of 3D printed polycaprolactone-bioactive glass composite scaffolds | |
| Karimi et al. | The effect of pore size and layout on mechanical and biological properties of 3D‐printed bone scaffolds with gradient porosity | |
| CN104441668B (en) | Nanometer artificial bone scaffold with structure similar to that of natural bone and preparation method thereof | |
| CN1886160A (en) | Bioresorbable composite material | |
| Arifvianto et al. | Characterization of the porous structures of the green body and sintered biomedical titanium scaffolds with micro-computed tomography | |
| EP3870133A1 (en) | Biological barrier membrane | |
| Liu et al. | Effects of incorporating carboxymethyl chitosan into PMMA bone cement containing methotrexate | |
| CN1164655C (en) | Preparation method of multi-layer high-molecular material | |
| Diaz-Gomez et al. | Three-dimensional extrusion printing of porous scaffolds using storable ceramic inks | |
| Wu et al. | Integrating pore architectures to evaluate vascularization efficacy in silicate-based bioceramic scaffolds | |
| CN104274860B (en) | A kind of preparation method of ceramic/polymer base Composite Bone support of controlled porous | |
| Carcassi et al. | Maximizing fiber content in 3D-printed earth materials: Printability, mechanical, thermal and environmental assessments | |
| Raja et al. | Support-less ceramic 3D printing of bioceramic structures using a hydrogel bath | |
| KR20180062132A (en) | Composition for three-dimensional ceramic scaffold having dual-pore | |
| CN1724081A (en) | Material of porous composite calcium sulfate with polymer for support and preparation process thereof | |
| CN1200043C (en) | Inorganic/organic nano-composite bioactivity porous material and its preparation method | |
| CN106139255A (en) | A kind of collagen protein combines new material and the preparation method of the medical sponge support of calcium phosphate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20030716 Assignee: Bo Sheng medical Limited by Share Ltd Assignor: Industrial Technology Research Institute Contract record no.: 2018990000304 Denomination of invention: Preparation method of multi-layer high-molecular material Granted publication date: 20040901 License type: Exclusive License Record date: 20181121 |
|
| EE01 | Entry into force of recordation of patent licensing contract | ||
| CX01 | Expiry of patent term |
Granted publication date: 20040901 |
|
| CX01 | Expiry of patent term |