CN103272284B - Biological medical controllable all-degradable material and preparation method thereof - Google Patents
Biological medical controllable all-degradable material and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a biological medical controllable all-degradable material and a preparation method thereof. The preparation method of the material comprises the following steps: 1) smelting and forming; 2) anodic polarization; and 3) coating. The material disclosed by the invention comprises a pure magnesium or magnesium alloy base and a functional film covered on the base surface with degradation protection and self-degradation characteristics; and the integral material has the characteristic of controllable all-degradable absorption, and satisfies the serious requirements for ideal characteristics of degradable biological materials. The invention provides a preferred scheme for solving the contradiction between biodegradable characteristic utilization and degradation rate control of the absorbable biological material, especially medical magnesium alloy; and the related material and technique are not only suitable for common medical appliance products, but also have competitive edges in manufacturing of high-end medical appliance products, such as implantation instruments, especially secondary-operation-free implantation substances.
Description
Technical field
The invention belongs to bio-medical new material and medical device product manufacture and applied technical field, relate in particular to a kind of bio-medical controllable full-degradable new material and preparation method thereof.
Background technology
Along with socioeconomic development and growth in the living standard, the mankind just unprecedentedly pay close attention to the medical treatment & health cause of self.The increasing of survival pressure, the quickening of rhythm of life, the aggravation of environmental pollution, the frequent generation of the security incidents such as food, traffic and production and local war, natural disaster etc., causes disease and wound to become the haze that the mankind can't get rid of forever.The important foundation of the important means as modern medicine---medical apparatus and instruments and ingredient, biomaterial is promoted for reparation, replacement or the function of the diagnosis of disease and treatment, histoorgan, and a large amount of struggle rehabilitated in sufferer residual, dead painful edge.In recent years, global medical apparatus industry high speed development, average annual growth rate be the same period increasing speed of national economy more than 2 times, be described as " rising industry ", become the very active new source of economic growth of 21 century.Take China as example, and China's Medical Device Market speedup in 2010 is up to 23%, and market scale breaks through 1,000 hundred million yuan of high point first, becomes the second-biggest-in-the-world Medical Device Market that is only second to the U.S., expects market scale in 2015 and will approach 3,400 hundred million yuan.Just because of biomaterial huge society and economic worth like this, its R&D work is subject to showing great attention to of countries in the world government, industrial circle and scientific and technological circle day by day, successively by U.S., moral, day, Australia and the Chinese government, is listed in the crucial new material development plan of high-tech.
Biomaterial is of a great variety, up to now, studied mistake exceed thousand kinds, extensively medical also have nearly hundred kinds.Wherein metal material is because of its intensity with the advantage such as fracture toughness is high, easily shape, and becomes especially most widely used load embedded material in orthopaedics (as backbone correcting, knochenbruch joint, skull repairing etc.) of current clinical medicine.Yet existing medical metal material as ubiquitous problems such as rustless steel, cochrome, nickel alloy and titanium alloys is: except expensive, mechanical compatibility, biocompatibility and biological degradability are also not fully up to expectations.The titanium alloy that obtains extensive use at clinical medicine of take at present is example, its main performance defect comprises: (1) is because elastic modelling quantity does not mate, cause the load conductive obstruction to adjacent bone tissue by implant, produce " stress shielding " effect, make its risk as implants (as suppressed knitting, cause osteoporosis, bone resorption or osteanabrosis, even occur secondary fracture etc.) cannot evade all the time; (2) degraded of pure titanium in body can cause allergy even dead, and the Al in typical titanium alloy ti6al4v and V all have cytotoxicity, and wherein V can cause chronic inflammatory disease, Al with Phos is combined, when causing phosphorus deficiency, also can bring out senile dementia; (3) because biological degradability is poor, at damaged tissues/organ, complete after reconstruction, implant must take out through second operation, has therefore blocked patient's rehabilitation process, has additionally increased its body and mind misery and financial burden.For these reasons, under the prerequisite that guarantees safety, find the better new material of combination property, new technique, be emphasis and the focus place of biomaterial research always.Under this overall background, magnesium alloy leaps to the visual field of material supply section scholar, clinical medicine expert and medical equipment new high-tech enterprise with its many advantages just.
Magnesium alloy is used the inherent advantage with a series of uniquenesses as bio-medical material: (one) biodegradation sexual clorminance.Magnesium metal chemical property is active, at aggressivity physiological environment (Cl
-, organic acid, protein, enzyme and cell etc.) effect under, magnesium implant in-service can be by progressively extremely finally disappearance completely of biodegradation, overcome metal body and in human body, retained for a long time caused complication, the Kucheng who makes patient avoid second operation is possible, means at same diseased region simultaneously and can repeatedly get involved intervention.(2) bio-compatible sexual clorminance.Magnesium is the non-dissident's composition of human body, is one of human body macroelement (Mg
2+in human body, to be only second to Na
+, K
+and Ca
2+occupy the 4th, in cell, be only second to K
+occupy the cation of the 2nd; Human body per weight magnesium average content 0.3-0.4g/kg), participate in a series of metabolic processes, closely related with the health of the maintaining of life, health, at biological phosphorus lime stone, form, bone matrix changes, osteocyte forms and in conjunction with, knitting, and very important role is all being played the part of in the normal performance aspect of the function such as nerve, muscle, heart.Therefore, magnesium metal is inanimate object toxicity in essence, while using as biomaterial, as long as effectively control the rate of release of magnesium ion, its degraded is to host useful and harmless (the daily demand of human body to magnesium: baby 40-70mg/d, child 250mg/d, adult 300-700mg/d).(3) mechanical compatibility advantage.Young ' the s elastic modelling quantity of magnesium is the most approaching with the corresponding parameter (10-40GPa) of skeleton, is conducive to reduce even eliminate implant to potential " stress shielding " effect of body bone tissue, promotes growth and the healing of bone.(4) biological activity advantage.Openly animal experiment and the clinical test results of report show, magnesium has excellent osteoinductive.(5) traditional performance advantage.Magnesium has " one is low " (density is low), " two height " (specific strength, specific stiffness is high), " three is good " (casting and machinability, dimensional stability and recyclable property are good) and " top four " (electromagnetic shielding ability, damping noise reduction ability and heat conduction, conductive capability is strong) feature, therefore enjoy the good reputation of " 21 century green engineering material ", in various fields especially in " lightweight ", " environmental protection " etc. is significant or has the field of special technical requirement, as Aero-Space, automobile, IT electronics, communication, the industrial departments such as national defense and military, magnesium alloy causes and shows great attention in the world as the Application and Development of structural material.(6) resource and price advantage.On the earth, magnesium resource is very abundant, and magnesium relative amount 10.63% in earth's crust metallic element is only second to aluminum (31.51%) and ferrum (22.02%) and occupies the 3rd, is 4.37 times of Ti content (2.43%).Wherein only in sea water, just there is the magnesium of " inexhaustible "---magnesium density 1.1kg/m
3, total content is up to 2.1 * 10
15ton.Developing rapidly of the technology such as rich in natural resources and smelting, shaping, relative titanium of price that causes magnesium metal and goods thereof etc. has seemed very cheap.Take raw material as example, and the statistical result of latest domestic market quotes shows, at present, the average price of 99.95% primary magnesium ingot (approximately 17.0 yuan/kg) is only (approximately 160.0 yuan/kg) 10% left and right of TA0 titanium ingot.Based on above-mentioned many advantages, magnesium alloy is expected to become desirable bio-medical metal new material, be used for comprising the orthopedic fixation device tools such as (1) hone lamella, nail and skeletal framework, (2) artificial bone, (3) intravascular stent and (4) tissue engineering bracket etc. are in the manufacture of interior many high added value medical device product.
But the poor (E of magnesium self thermodynamic stability regrettably,
0=-2.37V NHE), surperficial autoxidation film thin (~ 10nm) and loosen (because of PBR=0.80) and without " spontaneous recovery " ability, can not provide effective protection to matrix.It is reported, pure magnesium is through HBSS(Hank ' s balanced salt solution) erosion of 225h, mass loss is up to 99%.Therefore, the bio-medical of magnesium alloy is not only benefited from its unique biodegradation character, on the contrary, but lock into the too fast series of problems bringing of degraded always, as: a) material product military service performance especially the too early decay of mechanical integrity even lost efficacy, b) harm biocompatibility, c) heavy dose has the rapid release of the alloying element of potential source biomolecule toxicity, d) increase host's magnesium metabolism pressure, even cause hypermagnesemia, e) cause local pH value sharply soaring, and f) local organization pneumatosis, etc.For these reasons, development new material is the advanced composite material (ACM) based on magnesium or magnesium alloy especially, reinforcing material biodegradation controllability is (not only biodegradable, and degradation rate can regulate as required) time, improve the biocompatibility of material and even give its biological activity, to meet the harsh requirement of clinical medicine to material combination property, tool is of great significance, and becomes the important topic of bio-medical new material and medical instruments field.
Up to now, take biomedicine as application background, the exploitation of the Magnesium and magnesium alloys based composites technology of preparing based on surface modification has obtained great success.Relating to main process for modifying surface comprises: (1) conventional differential arc oxidation (MAO) technology (refer to take Nondegradable or almost without the MAO ceramic membrane of degradation capability as preparing the MAO technology of object, lower same), (2) complex technique based on conventional MAO, as MAO/ organic coat, MAO/ chemical deposition etc., (3) organic coat, (4) chemical conversion, (5) bionical passivation, (6) cathodic deposition, (7) anodic deposition, (8) IBAD(ion beam assisted depositing), (9) sol-gel process, (10) silane-modified, (11) ion implantation, (12) ion plating, (13) electrochemical polymerization, and (14) hydro-thermal method, Deng.Although above-mentioned technology and each tool advantage of composite making thereof, but also there is major defect: or be absorbed in the improvement to the inhibition of matrix biological degradability and biocompatibility, not only do not consider that surface reforming layer completes " the retiring from political life after winning tremendous successes " after reconstruction---biodegradation problem at damaged tissues/organ, on the contrary, for improving modified effect, but thinking is made an effort synthesize/applying in compactness, Nondegradable modified layer routinely; Although or with respect to the biological degradability of modified layer, comprehensive usage performance is unsatisfactory.With regard to the former, to utilize, the MAO of matrix is processed to the example that is prepared as that realizes composite, owing to adopting conventional electrolysis liquid (as silicate, phosphate and fluoride-based electrolyte), so gained MAO film main component is degradable or very poor silicate, phosphate or the fluoride of degradability hardly.This is impeccable beyond doubt for non-medical magnesium alloy, but with magnesium alloy bio-medical maximum bright spot---the utilization of biological degradability forms serious contradiction.In other words, when using as intravascular stent etc. as " exempting from second operation " implantation instrument or tubulose/chamber shape tissue/organ timbering material, even if environment lower substrate can progressively degrade, absorb according to expection under arms, Nondegradable housing (the surface modification rete such as MAO film) or its are peeled off the long-term existence of fragment, also by all effort that make to exempt the permanent external source precursor reactant of body, all that has been achieved is spoiled, even bringing on a disaster property consequence (as artery-clogging).With regard to the latter, in order to being used in matrix surface, apply the example that is prepared as that degradable high polymer material is realized composite, there is following subject matter: (1) does not consider the potential hazard of macromolecular material acid degradation product, as causing the acidify of local physiological environment, a. then causes aseptic inflammation, b. accelerate the degraded of magnesium alloy substrate, the tackle targetedly/protection measure that therefore has no proposition; (2) macromolecular material isolated use or only with Nondegradable HA(hydroxyapatite) compound use, limited its modified effect and application category; (3) coating/basal body binding force is undesirable, etc.
Summary of the invention
The object of the invention is to the subject matter existing in existing bio-medical material and application technology thereof, a kind of bio-medical controllable full-degradable new material and preparation method thereof is provided.
The present invention is achieved by the following technical programs:
A preparation method for bio-medical controllable full-degradable material, it comprises following key step:
A) melting and shaping: the pure magnesium of melting or magnesium alloy, and carry out figuration manufacture, obtain goods matrix;
B) anode polarization: step a) resulting product matrix is immersed in the group water solution of sodium chloride that concentration is 20.0mg/L-100.0g/L after surface dressing, take the goods of same material of homalographic as to electrode, energising is processed;
C) apply: comprise following key step:
C-1) preparation of solution:
1# solution: be the organic solvent based sols of PLLA, PLGA or its mixture, its concentration is 0.2-75.0g/L;
2# solution: for take magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture be solid dispersed phase, take water, acetone, ethanol, n-butyl alcohol or suspension that wherein two or more mixture are liquid, the concentration of wherein said solid dispersed phase is 0.5-45.0g/L;
3# solution: for take magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture be solid dispersed phase, the suspension that the organic solvent based sols of PLLA, PLGA or its mixture of take is liquid, the concentration of wherein said PLLA, PLGA or its mixture is 0.2-75.0g/L, and the quality of described solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass;
C-2) coating of coating: the goods matrix of processing through step b) is carried out to coating processing, obtain and to have degraded protection concurrently and from the functional membrane of degradation characteristic, described coating processing adopts more than one in following three kinds of schemes to carry out:
Scheme one: combine and use c-1) step is joined 1# solution and 2# solution, follows first with use the order of 1# solution after 1# solution with 2# solution again, carries out taking turns above coating;
Scheme two: the independent c-1 that uses) step is joined 3# solution and carried out taking turns above coating.
Scheme three: combine and use c-1) step is joined 1# solution, 2# solution and 3# solution, follows first with use the order of 3# solution after 1# solution with 2# solution again, carries out taking turns above coating.
Chile saltpeter for sodium chloride described in step b), sodium sulfate, lithium chloride, lithium nitrate, lithium sulfate, potassium chloride, potassium nitrate, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate, magnesium sulfate or wherein two or more mixture partly or entirely replace.
The organic solvent of the solution of 1# step c-1) and 3# solution is a kind of in A solvent and B solvent, wherein A solvent is more than one in epoxychloropropane, dichloromethane or chloroform, and B solvent is A solvent and more than one mixture that obtain after evenly mixing in acetone, ethanol or n-butyl alcohol; Step c-1) the pure Magnesium and magnesium alloys in the solution of 2# described in and 3# solution is Powdered, graininess, lamellar, thread, banded, tubulose or crystal whisker-shaped, and its OCP in any equivalent environment medium not higher than goods matrix in the OCP of pure magnesium or magnesium alloy.
Step c-1) for the solution of 1# described in, the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA replaces; Step c-1) solution of 3# described in order to magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture be solid dispersed phase, the suspension that the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA of take is liquid replaces, and the quality of wherein said solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass.
Step c-2) described in middle scheme one, 1# solution and a kind of of 2# solution replace with 3# solution; Step c-2) painting method described in comprises dip-coating, brushing, spin coating or spraying.
After the coating applying containing PLLA or PLGA, carry out spontaneous curing or artificial cured, until this coating layer portion or after solidifying completely, then carry out the coating of follow-up coating; When applying magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein after two or more mixture, carrying out dried.
The bio-medical controllable full-degradable material being made by above-mentioned preparation method, it comprise pure magnesium or magnesium alloy substrate and cover matrix surface have degraded protection concurrently and from the functional membrane of degradation characteristic; Described functional membrane comprises at least one in No.1 coating and No.2 coating; Described No.1 coating is for take magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or degradable high polymer material layer that wherein two or more mixture are sandwich of layers; Described No.2 coating is for take magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or degradable high polymer material based composites layer that wherein two or more mixture are wild phase, and the quality of wherein said wild phase accounts for the 0.5%-40% of composite quality; Degradable high polymer material in described No.1 coating and No.2 coating is PLLA, PLGA or its mixture.
More than described No.1 coating and No.2 coating are respectively one deck, and the composition of different layers, structure and thickness are identical or different; In described No.1 coating, composition, structure and the thickness of the degradable high polymer material layer of sandwich of layers both sides are identical or different; Sandwich of layers in described No.1 coating replaces by No.2 coating; In described No.1 coating, at least one deck of the degradable high polymer material layer of sandwich of layers both sides replaces by No.2 coating.
Pure Magnesium and magnesium alloys in described No.1 coating and No.2 coating is Powdered, graininess, lamellar, thread, banded, tubulose or crystal whisker-shaped, and its OCP in any equivalent environment medium is not higher than the OCP of the pure magnesium of matrix or magnesium alloy.
The melting of material preparation method step a) of the present invention and shaping can any known or commercially available technology be carried out, as: the melting under protective atmosphere, casting, forging and stamping, extruding or shaping by stock removal, etc.The effect of melting is to obtain the high-quality melt (metal or alloy liquid) that the level of controls such as chemical composition and field trash (as oxide inclusions), air content (as hydrogen) meet the demands; Shaping comprises and utilizes above-mentioned directly from melt formation (as casting) or be indirectly shaped (elder generation makes blank as ingot casting with above-mentioned melt, then blank is processed, as forging, extruding and cutting etc.).
In material preparation method step b) of the present invention, the object of surface dressing is to remove the burr, dirt, oxide skin of goods remained on surface or generation during processing, accumulating etc., to obtain, meets the surface quality that subsequent treatment requires.Surface dressing can any known or commercially available physics and/or chemical technology carry out, as sand paper/grinder buffing, polishing cloth polishing, organic solvent comprises dehydrated alcohol, acetone etc. directly or defat under the outer field actions such as ultrasound wave, alkali cleaning, pickling, washing, etc.
The main purpose of material preparation method step b) Anodic polarization of the present invention, be to realize matrix material is carried out to " deactivation " and surperficial roughening Duplex treatment, improving the corrosion proof while of material, for combining closely between coating/matrix established solid architecture basics.So-called " deactivation ", refers to and utilizes the selective dissolution effect of anode polarization that electro-chemical activity higher micro anode in matrix top layer is dissolved to " excavating ", leaves the micro cathode that electrochemistry inertia is stronger.When anode polarization is processed, power supply can be selected in direct current, interchange or the pulse power.Although also can be according to conventional way, use the inert materials such as rustless steel, graphite or platinized platinum as to electrode, and take the goods of same material of homalographic " take as to electrode " i.e. strategy of " equity is bipolar ", both can avoid heterogeneous to the potential contamination hazard of electrode pair electrolyte, again can be under the effect of symmetrical alternating current or the pulse power, guarantee that the two poles of the earth workpiece synchronization gain is close to consistent treatment effect, significantly improve the efficiency that anode polarization is processed, thereby farthest realize object energy-conservation, potentiation.As the goods to electrode, its geometry can be identical or different with workpiece.Certainly, using the material identical with workpiece when electrode material is used, also can be different from workpiece area to the area of electrode.The concrete technology parameter such as voltage/current amplitude, frequency and dutycycle, processing time during anode polarization, can require control flexibly according to the difference to treatment effect.In anode polarization electrolyte, sodium chloride concentration is too low, even if use high current density/action of high voltage long period, also cannot obtain gratifying treatment effect; Excessive concentration, cost of material there is no obvious benefit to the improvement for the treatment of effect when increasing, and therefore, the concentration of sodium chloride should be controlled to the scope of 20.0mg/L-100.0g/L.During anode polarization, solution temperature can be controlled in 1-85 ℃; Processing time can be according to the size that applies electrical quantity, the height of electrolyte concentration, and the specific requirement of surperficial roughening degree etc. is controlled flexibly.
After anode polarization finishes, the processing such as material preferably cleans respectively, is dried, comprise tap water and/or distilled water, rinsed with deionized water, hot blast or compressed air dry up or heating furnace is dried, or effumability organic solvent dries after as rinsings such as ethanol, acetone etc.Cleaning, dry object are to remove the non-target product that is adsorbed on surface of the work, comprise anode polarization by-product, anode polarization electrolyte etc., avoid solution cross-contamination and affect subsequent treatment effect.
In material preparation method step c) of the present invention, by the main purpose of various coating material liquefaction (being mixed with solution or fusing use), be conveniently to apply and guarantee to obtain the coating effect of homogeneous.The organic solvent of described PLLA, PLGA can be according to the specific requirements such as rate of dissolution, curing mode and speed and coating porosity, optimum selecting in A solvent, B solvent and other any known or commercially available solvent.When being mixed with the use of organic solvent based sols, the concentration of degradable high polymer material is too low, and the thick coating that single application obtains is spent thin, and coating efficiency is too low; Excessive concentration, solution viscosity is excessive, is unfavorable for that coating and coating uniformity are poor.The concrete concentration of degradable high polymer material, can require to control according to coating speed, coating quality (as uniformity, porosity etc.).When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture are used as the wild phase of degradable high polymer material based composites, consumption is too low, and modified effect is not obvious; Consumption is too high, causes composite coating overall performance to comprise cohesiveness, obviously worsen with basal body binding force and degraded barrier propterty etc.When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture are as 1) take the suspension that the organic solvent based sols of PLLA, PLGA or its mixture is liquid; or 2) take the solid dispersed phase of the suspension that the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA is liquid while using; by its quality control, at the 0.5%-40% that accounts for solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass, be the composite coating meeting the demands in order to ensure acquisition.During preparation 2# solution, controlling the wherein concentration of solid dispersed phase is 0.5-45.0g/L, and reason has two: one, and concentration is too low, and the thicknesses of layers that single application obtains is excessively thin, and coating efficiency is too low; Its two, excessive concentration, the homodisperse difficulty of solid dispersed phase strengthens and stability of solution variation, be unfavorable for applying and film quality poor.For obtaining high-quality suspension, the dispersion of described magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP can be carried out under the stirring conditions such as mechanical, ultrasonic or compressed air.While applying operation, the concrete coating number of times of every kind of coating material need to be controlled according to coating structure, thickness etc.When using identical coating material repeatedly to apply, each solution that applies use can be identical, also can be different.For identical coating solution, the coating layer thickness of acquisition and coating number of times positive correlation.
The technology such as the coating method of magnesium oxide of the present invention, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture can electrophoretic deposition, magnetron sputtering or ion beam assisted depositing replace.
It should be noted that, in material of the present invention, between functional membrane and matrix, may there is autoxidation thin film, be that matrix and surrounding (comprise atmosphere, cleaning solution is as water, dehydrated alcohol, alkali wash water or pickle etc., anode polarization solution etc.) during contact its top layer by autoxidation generated mainly by the rete of oxide, hydroxide (as magnesium oxide, magnesium hydroxide) or its compositions of mixtures of matrix.This " autoxidation thin film " is most metals and the inevitable outcome of alloy under conventional manufacturing environment (what answer in contrast is the special manufacturing environments such as vacuum) thereof, but because its thickness very thin (nanoscale) is conventionally substantially negligible on the impact of the general usage performance of material.
In material of the present invention and preparation method thereof, magnesium oxide used, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP can be the products of commercially available or homemade any shape, size and degree of crystallinity.Wherein pure Magnesium and magnesium alloys is advisable with Powdered, graininess, lamellar, thread, banded, tubulose or crystal whisker-shaped product especially.For strengthening the stability of pure Magnesium and magnesium alloys in coating, before use, can to it, carry out surface modification treatment by known or commercially available technology.In the coating of controlling preparation method and making, the OCP of pure magnesium or magnesium alloy is not higher than the OCP of pure magnesium or magnesium alloy in matrix, object is to obtain required coating and guarantees that under service state, coating ingredients is not as cathodic component, to accelerate the degraded of matrix, but preferably have precedence over matrix (as sacrificial anode), degrades.
In material of the present invention, No.1 coating and No.2 coated designs are more than one deck, and the composition (as: consumption of magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP or CPP of different layers (" different layers " here refer to take No.1 coating or No.2 coating be structural units); The kind of macromolecular material and molecular weight thereof etc.), structure (as density, porosity, surface roughness etc.) and thickness identical or different, in addition, the composition of the polymer material layer of sandwich of layers both sides in No.1 coating (kind and molecular weight thereof etc.), structure and thickness are identical or different, and its object is all that the characteristic that makes full use of different materials component units is to realize the successful control to material monolithic combination property especially biological degradability, biocompatibility and coating/basal body binding force, coating cohesiveness etc.In No.2 coating and No.1 coating, the concrete thickness of sandwich of layers and both sides polymer material layer thereof, can control according to actual needs flexibly.When carrying out the preparation of No.1 coating, for strengthening the adhesion of the polymer material layer of sandwich of layers and its both sides, the coating of sandwich of layers should be selected in before first floor polymer material layer solidifies completely to be carried out, or suitably control the porosity of the polymer material layer of sandwich of layers both sides, or after finishing, coating coating procedure heat-treats with suitable standard.
In material of the present invention and preparation method thereof, PLLA and PLGA can partly or entirely replace by any other known or commercially available macromolecular material with biodegradation character, as natural degradable macromolecular materials such as collagen protein, gelatin and chitosans, and other the absorbable macromolecule material.β-TCP and CPP also can partly or entirely replace by any other known or commercially available degradable inorganic bio.
It is pointed out that in the present invention, the pure magnesium of indication comprises: 1) the magnesium metal of different purity level, 2) pure magnesium goods, and 3) containing the goods of pure magnesium parts (constituent element).In the present invention, indication magnesium alloy comprises: the 1) magnesium base alloy of different-alloy constituent element and alloying level, 2) magnesium base composite material, and 3) magnesium alloy product, and 4) containing the goods of magnesium alloy component (constituent element).
Compared with prior art, advantage of the present invention is many-sided, and outstanding behaviours is aspect following two:
(1) material integrates ideal characterisitics with regard to the functional membrane part of material of the present invention, wherein degradable high polymer material transforms and hydrophobic property because biocompatibility is good and have fluid → solid, be not only desirable " binding agents " of non-block materials such as magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP, and it is good to possess cold/hot-forming property simultaneously, thickness, density and degradability etc. are controlled feature flexibly; Wherein magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP not only possess biodegradability, and catabolite is the nutrient of needed by human body.On the other hand, magnesium oxide, magnesium hydroxide, pure Magnesium and magnesium alloys also have with the acid degradation product of degradable high polymer material (as intermediate product lactic acid and end product carbon dioxide and the water of PLLA degraded) simultaneously neutralization reaction occur, and cushion/eliminate the outstanding role of its potential hazard (as aseptic inflammation etc.).In addition, wild phase as macromolecular material based composites, magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP not only can improve the mechanical property of matrix to a certain extent, and can improve largely the degraded barrier propterty of coating/basal body binding force and coating and regulate the degradation rate of coating.Based on above-mentioned analysis, functional membrane in material of the present invention not only has excellent biocompatibility and degraded protective (to matrix) concurrently, and self has controllable biodegradable---can be in moment as the effective effect passage of corrosive medium in blocking-up environment of implantation initial stage, matrix is formed to tight protection (degraded protection), can self degrade gradually along with the reconstruction of damaged tissues/organ again (degraded certainly), the final matrix that exposes is in order to its natural degradation, absorb, and its degraded protective capacities and all can pass through membranous layer ingredient from degradation rate, structure and thickness regulate and control.If the other parameters the same premise, functional membrane thickness is thicker, and its degraded protective capacities is stronger; Functional membrane structure is more loose, and its degraded protective capacities is more weak; Difficult degradation is got in functional membrane self constituent, and it is slower from degradation rate.And the body portion of material of the present invention---pure magnesium or magnesium alloy have biocompatibility, mechanical compatibility, biological degradability and biological activity concurrently, and its degradation rate can regulate and control as technology such as alloying, grain refinements by composition, microstructure optimization.Therefore, material monolithic of the present invention has obvious advantage---be expected to thoroughly eliminate current material ubiquitous or damage biocompatibility or mechanical integrity because putting undue emphasis on biological degradability, or damage the drawbacks such as biological degradability because putting undue emphasis on degraded protective, thereby provide desirable solution for the utilization of degradable biomaterial biodegradation character and the degradation rate contradiction between controlling.
(2) optimization that technology synergy is realized material is prepared material preparation method of the present invention based on to different materials, fully realizing of the advantage of different technologies and cooperative effect thereof, by forming technique and process for modifying surface organic composite, especially combine and utilize anode polarization and organic/inorganic paint-on technique, at matrix surface, construct coating/matrix, coating/painting interlayer is in conjunction with tight, composition, structure and thickness etc. are adjustable so degraded protection and controlled from degradation characteristic, there is excellent biocompatibility and bioactive multiple defense system simultaneously, for the preparation of bio-medical controllable full-degradable material provides new thinking.Particularly, containing aggressivity ion, carrying out anode polarization processing in as the electrolyte of chloride ion, nitrate ion or sulfate ion, by ionizing, there is anodic solution in the top layer metallic atom of pure magnesium or magnesium alloy.Inhomogeneities due to composition, microstructure etc., matrix microcell course of dissolution is inhomogeneous to carry out, anodic dissolution effect shows selectivity, be the optimum solvation of micro anode district, therefore, objectively, anode polarization not only has " deactivation " effect to matrix, and there is significant roughening effect, can form micro-" anchor point " in a large number, thereby be that combining closely between coating/matrix creates conditions.When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP are independently used as coating material, exist and apply the outstanding problems such as difficult, adhesion is poor, and the disperse phase (wild phase) of sandwich of layers using it as organic coating or macromolecular material based composites is when used, the problems referred to above are readily solved.Therefore, utilize technology provided by the invention, can realize the optimization preparation of controllable full-degradable material.
Accompanying drawing explanation
Fig. 1 is material preparation method process chart in embodiment;
Fig. 2 is material section structure schematic diagram in embodiment;
Fig. 3 is material function film section structure schematic diagram in embodiment;
In figure: 1-matrix, 2-functional membrane, a-degradable high polymer material layer, b-magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture layers, c-degradable high polymer material layer, d-be take magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or degradable high polymer material based composites layer that wherein two or more mixture are wild phase.
The specific embodiment
Below in conjunction with accompanying drawing and example, specific embodiment of the invention is described further, but enforcement of the present invention and protection domain are not limited to this.
As shown in Figure 1, be bio-medical controllable full-degradable material preparation method process chart of the present invention.The preparation method of material of the present invention consists of melting, the large key step of shaping → anode polarization → coating three.The object of wherein melting, shaping is to obtain the goods matrix that material (chemistry and phase composition, microstructure, grain size etc.), shape and size etc. meet the demands; The Main Function of anode polarization is to realize " deactivation " of goods matrix surface and " roughening " Duplex treatment; The effect applying is to construct functional membrane at matrix surface.
As shown in Figure 2, be material section structure schematic diagram of the present invention.Biological medical degradable material of the present invention is formed by pure magnesium or magnesium alloy substrate 1 and functional membrane 2 Integral constructions that cover matrix 1 surface.
As shown in Figure 3, be the functional membrane section structure schematic diagram of material of the present invention.Wherein a coating, b coating and c coating are superimposed, and belong to No.1 coating of the present invention, and b coating belongs to the sandwich of layers of No.1 coating.Wherein d coating belongs to No.2 coating of the present invention.
Below in conjunction with the preferred embodiments of the present invention, above-mentioned feature of the present invention is described in further detail.
In embodiment, material therefor comprises high purity magnesium (purity 99.9%), magnesium alloy AZ31, AZ91, WE43 and ZK60.According to material composition, carry out respectively melting, be shaped, obtain test specimen.Melting condition: temperature 750-760 ℃ wherein, 0.3vol%SF
6+ 50vol%CO
2mixed gas protected with air, melt holding time 30min.Forming technique comprises permanent mold casting (high purity magnesium and above-mentioned whole magnesium alloy), die casting (magnesium alloy AZ31 and AZ91), forges (magnesium alloy WE43) and hot extrusion (magnesium alloy AZ31 and ZK60), wherein permanent mold casting condition: 710-720 ℃; Die Casting Condition: 660 ℃ of pouring temperatures, 220 ℃ of type temperature, injection ratio pressure 50MPa, injection speed 40m/s; Forging condition: take cylindrical ingot casting as blank, open die forging, 400 ℃ of initial forging temperatures, 320 ℃ of final forging temperatures, forging ratio 1.87 is forged front 420 ℃ of insulation 2h at every turn; Hot extrusion condition: take cylindrical ingot casting as blank, 350 ℃ of extrusion temperatures, extrusion ratio 20, extruding rate 1.5m/min.Line cuts above-mentioned test specimen and obtains the test sample that is of a size of 20mm * 15mm * 2.5mm.By following standard, sample is carried out to surface dressing: alkali cleaning → washing → pickling → washing → silicon carbide paper polishing → washing → dehydrated alcohol successively from coarse to fine ultrasonic cleaning → hot blast drying → standby, wherein alkali cleaning condition: the combination solution of 40.0g/L sodium hydroxide, 10.0g/L sodium phosphate and 0.2g/L dodecylbenzene sodium sulfonate, 95 ℃, 15min; Acid washing conditions: the combination solution of 20.0g/L nitric acid, 50.0g/L magnesium nitrate and 50.0g/L dehydrated alcohol, 25 ℃, 15sec; Washing condition: tap water and distilled water rinsing successively.
Embodiment 1
The permanent mold casting state high purity magnesium sample of take is object of study.Take distilled water as solvent, and preparation 20.0g/L sodium chloride solution is as anode polarization electrolyte.After the homalographic sample of identical material is connected with wire, connect respectively two output ports of sinusoidal AC power supplies, and immerse in the above-mentioned electrolyte of 25 ℃ of temperature controls, keep sample spacing 3cm, 50Hz constant current 1.0mA/cm
2process 30min.After washing, being dried, find that specimen surface is uniformly distributed the hole in small, broken bits point that macroscopic size is consistent with the degree of depth.Take dichloromethane as solvent, and preparation 40.0g/LPLLA solution, is labeled as S
01; Take n-butyl alcohol as dispersant (liquid), add 10.0g/L magnesium oxide (solid dispersed phase), the acquisition suspension that stirs, is labeled as S
02; The homogeneous mixture (mixed volume is than 2:1) of epoxychloropropane and acetone of take is solvent, first prepares totally 5 parts of 25.0g/LPLLA solution (liquid), add respectively afterwards 5.0g/L magnesium oxide, magnesium hydroxide, pure magnesium powder (spherical, meta particle diameter d
50=47 μ m), β-TCP and CPP(solid dispersed phase), the acquisition suspension that stirs, is labeled as respectively solution S
03-1, S
03-2, S
03-3, S
03-4 and S
03-5.By following standard antianode polarization sample, carry out dip-coating processing: sample is immersed to solution S
01, after 7sec, take out, sample is immersed to suspension S after curing of coatings
02, after 15sec, take out, sample is immersed to solution S after drying up coating with cold wind
01, after 3sec, take out, treat that curing of coatings immerses solution S by sample
03after-1,10sec, take out, after curing of coatings, sample is immersed to solution S
01, after 3sec, take out, treat that curing of coatings immerses solution S by sample
03after-2,10sec, take out, after curing of coatings, sample is immersed to solution S
01, after 3sec, take out, treat that curing of coatings immerses solution S by sample
03after-3,10sec, take out, after curing of coatings, sample is immersed to solution S
01, after 3sec, take out, treat that curing of coatings immerses solution S by sample
03after-4,10sec, take out, after curing of coatings, sample is immersed to solution S
01, after 3sec, take out, treat that curing of coatings immerses solution S by sample
03after-5,10sec, take out, after curing of coatings, sample is immersed to solution S
01, after 3sec, take out, treat curing of coatings.Result obtains uniform composite coating (functional membrane) at anode polarization specimen surface, this coating is by 1) take the PLLA coating that magnesium oxide is sandwich of layers, and 2) take respectively the PLLA coating that PLLA based composites that magnesium oxide, magnesium hydroxide, pure magnesium, β-TCP or CPP be wild phase is sandwich of layers and be formed by stacking successively.
Take SBF(simulated body fluid) be tested media (its composition and human plasma chemical composition contrast situation are in Table 1), control appearance face than (ratio that ie in solution volume is long-pending with specimen surface) 24ml/cm
2, solution regeneration interval 24h, under 37 ℃ of conditions of probe temperature, carries out respectively in vitro biodegradation to said sample and can test.Result shows: sample matrix after about 21d just starts to occur macroscopic erosion trace, compare the result that starts corrosion after blank sample (only surface dressing and do not carry out the sample of anode polarization and coating processing) immerses, its initial stage, anti-degradation capability obviously strengthened, and showed that functional membrane has good biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 37d, shows that it has good in degradation characteristic; Sample is degradable after about 195d, shows that material monolithic has degradable characteristic.
Embodiment 2
The permanent mold casting state AZ31 magnesium alloy sample of take is object of study.Except electrolyte being changed into the sodium chloride solution of the 20.0mg/L preparing with deionized water, other condition of anode polarization is controlled with embodiment 1, found that: except pit density and degree of depth reduction, treatment effect is with embodiment 1.Except changing solvent into chloroform, solute PLLA changes into outside PLGA, solution S
01other condition of preparation is controlled with embodiment 1.Except magnesium oxide is changed into respectively magnesium hydroxide, pure magnesium powder (spherical, meta particle diameter d
50=47 μ m), outside β-TCP or CPP, solution S
02other condition of preparation is controlled with embodiment 1, and corresponding solution is labeled as respectively S
02-1, S
02-2, S
02-3 and S
02-4.By following standard, washing, dried anode polarization sample are carried out to dip-coating processing: sample is immersed to solution S
01, after 7sec, take out, after curing of coatings, sample is immersed to solution S
02after-1,15sec, take out, sample is immersed to solution S after drying up coating with cold wind
01, after 3sec, take out, after curing of coatings, sample is immersed to solution S
02after-2,10sec, take out, sample is immersed to solution S after drying up coating with cold wind
01, after 3sec, take out, after curing of coatings, sample is immersed to solution S
02after-3,10sec, take out, sample is immersed to solution S after drying up coating with cold wind
01, after curing of coatings, sample is immersed to solution S
02after-4,10sec, take out, sample is immersed to solution S after drying up coating with cold wind
01, treat curing of coatings.Result obtains uniform coating (functional membrane) at specimen surface, and this coating is formed by stacking successively by take respectively the PLGA coating that magnesium hydroxide, pure magnesium, β-TCP and CPP be sandwich of layers.With embodiment 1, carry out the test of material bodies outside biodegradability, result shows: sample matrix after about 14d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 30d, shows that it has good in degradation characteristic; Sample is degradable after about 90d, shows that material monolithic has degradable characteristic.
Embodiment 3
The permanent mold casting state AZ91 magnesium alloy sample of take is object of study.Except 100.0g/L sodium chloride solution electrolyte being changed into distilled water preparation, other condition of anode polarization is controlled with embodiment 1, found that: except single pit area increases, and outside pit density and distributing homogeneity thereof reduce, the other the same as in Example 1.With embodiment 1, carry out solution S
03-1 preparation.With this solution to through washing, dried anode polarization sample brushes respectively, spin coating and spray treatment, acquisition surface density is 1.75mg/cm
2uniform magnesium oxide/PLLA composite coating (functional membrane).With embodiment 1, carry out the test of material bodies outside biodegradability, result shows: sample matrix after about 42d just starts to occur macroscopic erosion trace, shows that functional membrane has good biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 75d, shows that it has good in degradation characteristic; Sample is degradable after about 170d, shows that material monolithic has degradable characteristic.
Embodiment 4
The permanent mold casting state WE43 magnesium alloy sample of take is object of study.Except the sodium chloride in electrolyte is changed into respectively Chile saltpeter, sodium sulfate, lithium chloride, lithium nitrate, lithium sulfate, potassium chloride, potassium nitrate, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate or magnesium sulfate, other condition control of anode polarization and result are with embodiment 1.The homogeneous mixture (mixed volume is than 4:1) of chloroform and dehydrated alcohol of take is solvent, prepare 5.0,10.0,15.0 and 20.0g/LPLLA solution first respectively, then mechanical agitation limit in limit adds 10.0g/L magnesium hydroxide, obtains suspension after mix homogeneously, is labeled as solution S
04-1, S
04-2, S
04-3 and S
04-4.By following standard, washing, dried anode polarization sample are carried out to dip-coating processing: sample is immersed to solution S
04after-Isosorbide-5-Nitrae 5sec, take out, after curing of coatings, sample is immersed to solution S
04after-2,30sec, take out, after curing of coatings, sample is immersed to solution S
04after-3,45sec, take out, after curing of coatings, sample is immersed to solution S
04after-4,30sec, take out, treat curing of coatings.Result obtains uniformly at specimen surface the composite coating (functional membrane) that PLLA matrix composite coating that the magnesium hydroxide by different content is wild phase is formed by stacking.With embodiment 1, carry out the test of material bodies outside biodegradability, result shows: sample matrix after about 20d just starts to occur macroscopic erosion trace, shows that functional membrane has good biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 45d, shows that it has good in degradation characteristic; Sample is degradable after about 120d, shows that material monolithic has degradable characteristic.
Embodiment 5
The permanent mold casting state ZK60 magnesium alloy sample of take is object of study.Anode polarization process regulation and result are with embodiment 1.The homogeneous mixture (mixed volume is than 3:1) of epoxychloropropane and acetone of take is solvent, and preparation 75.0g/LPLLA solution, is labeled as S
05; Take ethanol as dispersant (liquid), add 45.0g/L magnesium hydroxide (solid dispersed phase), the acquisition suspension that stirs, is labeled as S
06; Take chloroform as solvent, first prepare 75.0g/LPLLA solution, then add the magnesium hydroxide of 0.377g/L, the acquisition suspension that stirs, is labeled as S
07.By following standard, washing, dried anode polarization sample are carried out 7 and take turns dip-coating processing: sample is immersed to solution S
05in, after 20sec, take out, after curing of coatings, sample is immersed to solution S
06in, after 10sec, take out, after coating is dry, sample is immersed to solution S
05in, after 45sec, take out, after curing of coatings, sample is immersed to solution S
07, after 30sec, take out, after curing of coatings, sample is immersed to solution S
05in, after 45sec, take out, treat curing of coatings.Result obtains uniform composite coating (functional membrane) at specimen surface, and this coating is by 1) take the PLLA coating that magnesium hydroxide is sandwich of layers, 2) take the PLLA coating that magnesium hydroxide/PLLA composite is sandwich of layers and be formed by stacking successively.With embodiment 1, carry out the test of material bodies outside biodegradability, result shows: sample matrix after about 37d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 85d, shows that it has good in degradation characteristic; Sample is degradable after about 130d, shows that material monolithic has degradable characteristic.
Embodiment 6
The die casting AZ91 magnesium alloy sample of take is object of study.Anode polarization process regulation and result are with embodiment 1.Except changing PLLA concentration into 0.2g/L, magnesium hydroxide concentration changes into outside 0.5g/L, solution S
05and S
06other condition of preparation is controlled with embodiment 5.Except changing PLLA concentration into 0.2g/L, magnesium hydroxide concentration changes into outside 0.133g/L, solution S
07other condition of preparation is controlled with embodiment 5.With 5 pairs of washings of embodiment, dried anode polarization sample, apply, result is with embodiment 5.With embodiment 1, carry out the test of material bodies outside biodegradability, result shows: sample matrix after about 12d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 25d, shows that it has good in degradation characteristic; Sample is degradable after about 147d, shows that material monolithic has degradable characteristic.
Embodiment 7
The forging WE43 magnesium alloy sample of take is object of study.Anode polarization process regulation and result are with embodiment 1.With embodiment 1, carry out solution S
02preparation.PLLA solid particle is heated to complete molten condition 210 ℃ of insulations, is labeled as solution S
08.By following standard, washing, dried anode polarization sample are carried out to dip-coating processing: sample is immersed to solution S
08, after 30sec, take out, after curing of coatings, sample is immersed to solution S
02, after 15sec, take out, after coating is dry, sample is immersed to solution S
08, after 2sec, take out, treat curing of coatings.Result obtains and take the PLLA coating that magnesium oxide is sandwich of layers uniformly at specimen surface.With embodiment 1, carry out the test of material bodies outside biodegradability, result shows: sample matrix after about 5d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 12d, shows that it has good in degradation characteristic; Sample is degradable after about 100d, shows that material monolithic has degradable characteristic.
Embodiment 8
The As-extruded AZ31 magnesium alloy sample of take is object of study.Anode polarization process regulation and result are with embodiment 1.190.0gPLLA solid particle is heated to complete molten condition 210 ℃ of insulations, adds the mixture of 5.0g magnesium oxide and 5.0g magnesium hydroxide, the acquisition suspension that stirs, is labeled as solution S
09.By following standard, washing, dried anode polarization sample are carried out to dip-coating processing: sample is immersed to solution S
09, after 45sec, take out, after curing of coatings, sample is immersed to solution S
09, after 3sec, take out, treat curing of coatings.Result obtains and take the PLLA matrix composite coating that magnesium oxide and magnesium hydroxide is wild phase uniformly at specimen surface.With embodiment 1, carry out the test of material bodies outside biodegradability, result shows: sample matrix after about 10d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 23d, shows that it has good in degradation characteristic; Sample is degradable after about 130d, shows that material monolithic has degradable characteristic.
Embodiment 9
The die casting state AZ31 magnesium alloy sample of take is object of study.Anode polarization process regulation and result are with embodiment 1.Take chloroform as solvent, and preparation 5.0,10.0,15.0,20.0 and 25.0g/LPLLA solution, be labeled as respectively solution S
10-1, S
10-2, S
10-3, S
10-4 and S
10-5; Take ethanol as dispersant (liquid), add 10.0g/L magnesium hydroxide (solid dispersed phase) the acquisition suspension that stirs, be labeled as S
11.By following standard, washing, dried anode polarization sample are carried out to dip-coating processing: sample is immersed to solution S
10after-1,15sec, take out, after curing of coatings, sample is immersed to solution S
11, after 3sec, take out, after curing of coatings, sample is immersed to solution S
10after-2,15sec, take out, after curing of coatings, sample is immersed to solution S
11, after 3sec, take out, after curing of coatings, sample is immersed to solution S
10after-3,15sec, take out, after curing of coatings, sample is immersed to solution S
11, after 3sec, take out, treat that curing of coatings immerses solution S by sample
10after-4,15sec, take out, after curing of coatings, sample is immersed to solution S
11, after 3sec, take out, after curing of coatings, sample is immersed to solution S
10after-5,15sec, take out, after curing of coatings, sample is immersed to solution S
11, after 3sec, take out, treat curing of coatings.Result obtains and take the PLLA coating that magnesium hydroxide is sandwich of layers uniformly at specimen surface, and the feature of this coating is that the PLLA of sandwich of layers both sides has different thickness.With embodiment 1, carry out the test of material bodies outside biodegradability, result shows: sample matrix after about 17d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 32d, shows that it has good in degradation characteristic; Sample is degradable after about 127d, shows that material monolithic has degradable characteristic.
Embodiment 10
The As-extruded ZK60 magnesium alloy sample of take is object of study.The control of anode polarization condition and result are with embodiment 1.With embodiment 1, carry out solution S
01, S
02and S
03-1 preparation.By following standard, washing, dried anode polarization sample are carried out to dip-coating processing: sample is immersed to solution S
03after-1,60sec, take out, after curing of coatings, sample is immersed to solution S
02, after 15sec, take out, after coating is dry, sample is immersed to solution S
03after-1,20sec, take out, after curing of coatings, sample is immersed to solution S
02, after 15sec, take out, sample is immersed to solution S
01, after 30sec, take out, treat curing of coatings.Result obtains composite coating (functional membrane) at specimen surface, this coating is by 1) take magnesium oxide/PLLA composite coating that magnesium oxide is sandwich of layers, with 2) take magnesium oxide as sandwich of layers, the coating that both sides are respectively magnesium oxide/PLLA composite coating and PLLA coating is formed by stacking.With embodiment 1, carry out the test of material bodies outside biodegradability, result shows: sample matrix after about 6d just starts to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane disappears substantially completely after about 15d, shows that it has good in degradation characteristic; Sample is degradable after about 100d, shows that material monolithic has degradable characteristic.
With further reference to BiologicalEvaluationofMedicalDevice ISO 10993 standards, with the negative contrast of widely used titanium alloy ti6al4v on clinical medicine, each sample in above-described embodiment is carried out respectively take the biocompatibility test that hemolysis rate and vitro cytotoxicity are representative, and result shows: each sample all shows the good biocompatibility suitable with Ti6Al4V.
Table 1: tested media and the contrast of human plasma chemical composition
Claims (9)
1. a preparation method for bio-medical controllable full-degradable material, is characterized in that comprising following key step:
A) melting and shaping: the pure magnesium of melting or magnesium alloy, and carry out figuration manufacture, obtain goods matrix;
B) anode polarization: step a) resulting product matrix is immersed in the group water solution of sodium chloride that concentration is 20.0mg/L-100.0g/L after surface dressing, take the goods of same material of homalographic as to electrode, energising is processed;
C) apply: comprise following key step:
C-1) preparation of solution:
1# solution: be the poly-left lactic acid of PLLA(), PLGA(poly lactic-co-glycolic acid) or the organic solvent based sols of its mixture, its concentration is 0.2-75.0g/L;
2# solution: for take magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP(bata-tricalcium phosphate), CPP(calcium polyphosphate) or wherein two or more mixture are solid dispersed phase, take water, acetone, ethanol, n-butyl alcohol or suspension that wherein two or more mixture are liquid, the concentration of wherein said solid dispersed phase is 0.5-45.0g/L;
3# solution: for take magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture be solid dispersed phase, the suspension that the organic solvent based sols of PLLA, PLGA or its mixture of take is liquid, the concentration of wherein said PLLA, PLGA or its mixture is 0.2-75.0g/L, and the quality of described solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass;
C-2) coating of coating: the goods matrix of processing through step b) is carried out to coating processing, obtain and to have degraded protection concurrently and from the functional membrane of degradation characteristic, described coating processing adopts more than one in following three kinds of schemes to carry out:
Scheme one: combine and use c-1) step is joined 1# solution and 2# solution, follows first with use the order of 1# solution after 1# solution with 2# solution again, carries out taking turns above coating;
Scheme two: the independent c-1 that uses) step is joined 3# solution and carried out taking turns above coating;
Scheme three: combine and use c-1) step is joined 1# solution, 2# solution and 3# solution, follows first with use the order of 3# solution after 1# solution with 2# solution again, carries out taking turns above coating.
2. the preparation method of bio-medical controllable full-degradable material according to claim 1, is characterized in that: Chile saltpeter for sodium chloride described in step b), sodium sulfate, lithium chloride, lithium nitrate, lithium sulfate, potassium chloride, potassium nitrate, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate, magnesium sulfate or wherein two or more mixture partly or entirely replace.
3. the preparation method of bio-medical controllable full-degradable material according to claim 1, it is characterized in that: the organic solvent of the solution of 1# step c-1) and 3# solution is a kind of in A solvent and B solvent, wherein A solvent is more than one in epoxychloropropane, dichloromethane or chloroform, and B solvent is A solvent and more than one mixture that obtain after evenly mixing in acetone, ethanol or n-butyl alcohol; Step c-1) the pure Magnesium and magnesium alloys in the solution of 2# described in and 3# solution is Powdered, graininess, lamellar, thread, banded, tubulose or crystal whisker-shaped, and its OCP in any equivalent environment medium not higher than goods matrix in the OCP of pure magnesium or magnesium alloy.
4. the preparation method of bio-medical controllable full-degradable material according to claim 1, is characterized in that: for the solution of 1# step c-1), the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA replaces; Step c-1) solution of 3# described in order to magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixture be solid dispersed phase, the suspension that the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA of take is liquid replaces, and the quality of wherein said solid dispersed phase accounts for the 0.5%-40% of solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass.
5. the preparation method of bio-medical controllable full-degradable material according to claim 1, is characterized in that: step c-2) described in middle scheme one, 1# solution and a kind of of 2# solution replace with 3# solution; Step c-2) painting method described in comprises dip-coating, brushing, spin coating or spraying.
6. the preparation method of bio-medical controllable full-degradable material according to claim 1, it is characterized in that: after the coating applying containing PLLA or PLGA, carry out spontaneous curing or artificial cured, until this coating layer portion or after solidifying completely, then carry out the coating of follow-up coating; When applying magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein after two or more mixture, carrying out dried.
7. the bio-medical controllable full-degradable material being made by preparation method claimed in claim 1, it is characterized in that comprising pure magnesium or magnesium alloy substrate and cover matrix surface have degraded protection concurrently and from the functional membrane of degradation characteristic; Described functional membrane comprises at least one in No.1 coating and No.2 coating; Described No.1 coating is for take magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or degradable high polymer material layer that wherein two or more mixture are sandwich of layers; Described No.2 coating is for take magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or degradable high polymer material based composites layer that wherein two or more mixture are wild phase, and the quality of wherein said wild phase accounts for the 0.5%-40% of composite quality; Degradable high polymer material in described No.1 coating and No.2 coating is PLLA, PLGA or its mixture.
8. bio-medical controllable full-degradable material according to claim 7, is characterized in that: more than described No.1 coating and No.2 coating are respectively one deck, and the composition of different layers, structure and thickness are identical or different; In described No.1 coating, composition, structure and the thickness of the degradable high polymer material layer of sandwich of layers both sides are identical or different; Sandwich of layers in described No.1 coating replaces by No.2 coating; In described No.1 coating, at least one deck of the degradable high polymer material layer of sandwich of layers both sides replaces by No.2 coating.
9. bio-medical controllable full-degradable material according to claim 7, it is characterized in that: the pure Magnesium and magnesium alloys in described No.1 coating and No.2 coating is Powdered, graininess, lamellar, thread, banded, tubulose or crystal whisker-shaped, and its OCP in any equivalent environment medium is not higher than the OCP of the pure magnesium of matrix or magnesium alloy.
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