CN103286053A - Biomedical material and preparation method thereof - Google Patents

Abstract

The invention discloses biomedical material and a preparation method thereof. The preparation method includes: 1, melting and forming; 2, polarizing an anode; 3, depositing the anode; 4, performing thermal treatment; 5, coating. The biomedical material comprises a pure magnesium or magnesium-alloy base and a functional film which covers the surface of the base and which has the functions of degradation protection and self-degradation. The biomedical material features controllability, full degradation and full absorption, and the strict requirements for ideal features of the degradable biomaterial are met. The biomedical material has the advantages that an optimal solution is provided for the absorbable biomedical material, especially the contradiction between biodegradability and degrading speed control in medical magnesium alloy, and related materials and techniques are applicable to common medical instruments and are more competitive in production of high-end medical instruments, such as implant instruments, especially 'secondary-operation-free' implants.

Description

A kind of bio-medical material and preparation method thereof

Technical field

The invention belongs to bio-medical new material and medical device product manufacturing and applied technical field, relate in particular to a kind of bio-medical new material and preparation method thereof.

Background technology

Along with The development in society and economy and growth in the living standard, the human medical treatment ﹠ health cause of just unprecedentedly paying close attention to self.The increasing of survival pressure, the quickening of rhythm of life, the aggravation of environmental pollution, the frequent generation of security incident such as food, traffic and production and local war, natural calamity etc. causes disease and wound to become human haze of can't get rid of forever.The important foundation of the important means as modern medicine---medicine equipment and part, biomaterial are used for reparation, replacement or the function of the diagnosis of disease and treatment, histoorgan to be promoted, and a large amount of struggles are 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.Be example with China, China medicine equipment 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 medicine equipment market that is only second to the U.S., and expecting market scale in 2015 will be near 3,400 hundred million yuan.Just because of biomaterial huge social like this and economic worth, its R﹠D work is subjected to showing great attention to of countries in the world government, industrial circle and scientific and technological circle day by day, is successively listed in the crucial new material development plan of high-tech by U.S., moral, day, Australia and the Chinese government.

Biomaterial is of a great variety, and up to now, what be studied exceedes thousand kinds, and extensive medical also has nearly hundred kinds.Wherein metal material is because of its intensity and fracture toughness height, easily advantage such as shape, and becomes especially most widely used load embedded material in the orthopaedics (as backbone correcting, knochenbruch joint, skull repairing etc.) of present clinical medicine.Yet existing medical metal material such as ubiquitous problems such as stainless steel, cochrome, nickel alloy and titanium alloy are: except expensive, mechanical compatibility, biocompatibility and biological degradability are also not fully up to expectations.Be example with the titanium alloy that at present obtained extensive use at clinical medicine, its main performance defective comprises: (1) does not match owing to elastic modelling quantity, cause by the load conductive obstruction of implant to adjacent bone tissue, namely produce " stress shielding " effect, make its risk as implants (as suppressing knitting, cause osteoporosis, bone to absorb or osteanabrosis, even secondary fracture etc. occurs) can't evade all the time; (2) degraded of pure titanium in body can cause allergy even death, and the Al in the typical titanium alloy ti6al4v and V all have cytotoxicity, and wherein V can cause chronic inflammation, and Al is combined with Phos, also can bring out senile dementia when causing lacking phosphorus; (3) because biological degradability is poor, and after damaged tissues/organ was finished reconstruction, implant must take out through second operation, therefore block the rehabilitation of patients process, additionally increased its body and mind misery and financial burden.For these reasons, seek better new material, the new technology of combination property under the prerequisite that guarantees security, 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 advantage just.

Magnesium alloy uses the inherent advantage with a series of uniquenesses as bio-medical material: (one) biodegradation sexual clorminance.The magnesium metal chemical property is active, at aggressivity physiological environment (Cl ^-, organic acid, protein, enzyme and cell etc.) effect under, the magnesium implant in-service can be by the progressively extremely last complete obiteration of biodegradation, overcome metal body and in human body, retained the complication that causes for a long time, the Kucheng who makes the patient avoid second operation is possible, means simultaneously at same diseased region 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⁺Be to be only second to Na in the human body ⁺, K ⁺And Ca ²⁺Occupy the 4th, be only second to K in the cell ⁺Occupy the 2nd cation; Human body per weight magnesium average content 0.3-0.4g/kg), participate in a series of metabolic processes, healthy closely related with the keeping of life, health, form at the biological phosphorus lime stone, 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 functions such as nerve, muscle, heart.Therefore, the magnesium metal is inanimate object toxicity in essence, when using as biomaterial, as long as effectively control the rate of release of magnesium ion, then its degraded is to host useful and harmless (human body is to the daily demand of magnesium: baby 40-70mg/d, children 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 eliminates implant to potential " stress shielding " effect of body bone tissue, promotes growth and the healing of bone.(4) biologically active advantage.Animal experiment and the clinical test results of open report show that magnesium has excellent osteoinductive.(5) traditional performance advantage.Magnesium has " one is low " (density is low); " two-supremes " (specific strength; the specific stiffness height); " 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) characteristics; therefore enjoy the good reputation of " 21 century green engineering material "; in various fields especially in " lightweight "; " environmental protectionization " etc. is significant or the field of special technical requirement arranged; as Aero-Space; automobile; the IT electronics; communication; industrial departments such as national defense and military, magnesium alloy cause in the world as the Application and Development of structural material shows great attention to.(6) resource and price advantage.Magnesium resource is very abundant on the earth, and magnesium relative amount 10.63% in the earth's crust metallic element is only second to aluminium (31.51%) and iron (22.02%) and occupies the 3rd, is 4.37 times of Ti content (2.43%).The magnesium that " inexhaustible " wherein only just arranged in the seawater---magnesium density 1.1kg/m ³, total content is up to 2.1 * 10 ¹⁵Ton.Technology rapid development 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.Be example with raw material, latest domestic market quotes statistics shows, at present, the average price of 99.95% primary magnesium ingot (about 17.0 yuan/kg) only be (about 160.0 yuan/kg) about 10% 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 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 manufacturing 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) loosen (because of PBR=0.80) and do not have " self-healing " ability, can not provide effective protection to matrix.It is reported that 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 biological degradation characteristic, on the contrary, but lock into the too fast serial problem of bringing of degraded always, as: a) especially too early decay even the inefficacy of mechanical integrity of material product military service performance, 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 initiation hypermagnesemia, e) cause the local pH value sharply soaring, and f) the local organization pneumatosis, etc.For these reasons, the development new material is especially based on the advanced composite material (ACM) of magnesium or magnesium alloy, reinforcing material biodegradation controllability is (not only biodegradable, and degradation rate can be regulated as required) time, improve the biocompatibility of material even give its biologically active, to satisfy clinical medicine to the harsh requirement of material combination property, have very important meaning, become the important topic of bio-medical new material and medical instruments field.

Up to now, be application background with the biomedicine, obtained great success based on the magnesium of surface modification and the exploitation of magnesium alloy composite technology of preparing.Relating to main process for modifying surface comprises: (1) conventional differential arc oxidation (MAO) technology (refers to nondegradation or the MAO ceramic membrane that almost do not have a degradation capability is the MAO technology of preparation object, down together), (2) based on the complex technique of conventional MAO, as the 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 injects, (12) ion plating, (13) electrochemical polymerization, and (14) hydro-thermal method, etc.Though above-mentioned technology and each the tool advantage of composite that makes thereof, but also there is major defect: or be absorbed in the inhibition of matrix biological degradability and the improvement of biocompatibility, not only do not consider surface reforming layer " retiring from political life after winning tremendous successes " after damaged tissues/organ is finished reconstruction---biodegradation problem, on the contrary, be to improve modified effect, but routinely thinking synthesize/apply compactness, the nondegradation modified layer is worked hard; Though or with respect to the biological degradability of modified layer, comprehensive usage performance is unsatisfactory.With regard to the former, to utilize the MAO to matrix to handle the example that is prepared as that realizes composite, owing to adopt 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 the magnesium alloy bio-medical maximum bright spot---the utilization of biological degradability constitutes serious contradiction.In other words, when using as " exempting from second operation " implantation instrument or tubulose/chamber shape tissue/organ timbering material such as intravascular stent etc., even the environment lower substrate can progressively degrade, absorb according to expection under arms, nondegradation housing (surface modification rete such as MAO film) or its are peeled off the long-term existence of fragment, all that has been achieved is spoiled also will to make all effort of exempting the permanent external source precursor reactant of body, even bringing on a disaster property consequence (as artery-clogging).With regard to the latter, apply the example that is prepared as that degradable high polymer material is realized composite in order to being used in matrix surface, have following subject matter: (1) does not consider the potential hazard of macromolecular material acid degradation product, cause the acidifying of local physiological environment to cause aseptic inflammation then as a., therefore b. accelerate the degraded of magnesium alloy substrate, do not see that proposition tackles/protection measure targetedly; (2) macromolecular material isolated use or only with nondegradation 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 objective of the invention is to the outstanding problem that exists in existing bio-medical material and the application technology thereof, a kind of bio-medical new material and preparation method thereof is provided.

The present invention is achieved by the following technical programs:

A kind of preparation method of bio-medical material, it comprises following key step:

A) melting and shaping: the pure magnesium of melting or magnesium alloy, and form manufacturing, obtain the goods matrix;

B) anode polarization: step a) resulting product matrix is immersed behind surface dressing in the group water solution of sodium chloride that concentration is 20.0mg/L-100.0g/L, is to electrode with the goods of the same material of homalographic, and energising is handled;

C) cathodic deposition: will immerse in the group water solution of magnesium chloride that concentration be 0.5-150.0g/L through goods matrix that step b) was handled, energising is handled, and obtains to have concurrently the degraded protection and from the prefilter layer of the functional membrane bottom of degradation characteristic;

D) heat treatment: the goods matrix of handling through step c) is heat-treated, obtain to have concurrently the degraded protection and from the functional membrane bottom of degradation characteristic, wherein said heat treatment temperature is 350-550 ℃, temperature retention time is 1-24h;

E) apply: comprise following key step:

E-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 magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be solid dispersed phase, with water, acetone, ethanol, n-butanol or wherein two or more mixtures be the suspension of liquid, the concentration of wherein said solid dispersed phase is 0.5-45.0g/L;

3# solution: for magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be solid dispersed phase, organic solvent based sols with PLLA, PLGA or its mixture is the suspension of 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;

E-2) coating of coating: the goods matrix of handling through step d) is carried out coating processing, obtain to have concurrently the degraded protection and from the functional membrane surface layer of degradation characteristic, described coating processing adopts in following three kinds of schemes more than one to carry out:

Scheme one: unite and use e-1) step is joined 1# solution and 2# solution, follows elder generation with the order of using 1# solution behind the 1# solution with 2# solution again, carries out taking turns above coating;

Scheme two: the independent e-1 that uses) step is joined 3# solution and is carried out taking turns above coating;

Scheme three: unite and use e-1) step is joined 1# solution, 2# solution and 3# solution, follows elder generation with the order of using 3# solution behind the 1# solution with 2# solution again, carries out taking turns above coating.

Sodium chloride described in the step b) with sodium nitrate, sodium sulphate, 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 mixtures partly or entirely replace; Magnesium chloride described in the step c) partly or entirely replaces with magnesium nitrate, magnesium sulfate or its mixture.

The organic solvent of the solution of 1# step e-1) and 3# solution is a kind of in A solvent and the B solvent, wherein the A solvent is more than one in epoxychloropropane, carrene or the chloroform, the B solvent be the A solvent with acetone, ethanol or n-butanol in more than one mixtures that obtain after evenly mixing; Step e-1) the pure magnesium in the solution of 2# described in and the 3# solution and magnesium alloy are Powdered, graininess, sheet, thread, banded, tubulose or whisker shape, and its OCP in any equivalent environment medium is not higher than the OCP of pure magnesium in the goods matrix or magnesium alloy.

Step e-1) solution of 1# described in replaces with the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA; Step e-1) solution of 3# described in order to magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be solid dispersed phase, mixture with molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA is the suspension replacement of liquid, 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 e-2) a kind of of scheme one described 1# solution and 2# solution replaces with 3# solution in; Step e-2) painting method described in comprises dip-coating, brushing, spin coating or spraying.

Contain the coating of PLLA or PLGA when coating after, carry out spontaneous curing or artificial curing handled, after treating this coating layer portion or solidifying fully, carry out the coating of follow-up coating again; When applying magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein behind the two or more mixtures, carrying out drying processing.

A kind of bio-medical material that is made by above-mentioned preparation method, it comprise pure magnesium or magnesium alloy substrate and cover matrix surface have the degraded protection concurrently and from the functional membrane of degradation characteristic, wherein functional membrane comprises bottom and surface layer; Described bottom mainly is made up of the mixture of magnesia or magnesia and magnesium hydroxide; Described surface layer comprises in No.1 coating and the No.2 coating at least a; Described No.1 coating for magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be the degradable high polymer material layer of sandwich of layers; Described No.2 coating for magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be the degradable high polymer material based composites layer of wild phase, 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 the No.2 coating is PLLA, PLGA or its mixture.

Described No.1 coating and No.2 coating are respectively more than one deck, and the composition of different layers, structure and thickness are identical or different; Composition, structure and the thickness of the degradable high polymer material layer of sandwich of layers both sides are identical or different in the described No.1 coating; Sandwich of layers in the described No.1 coating replaces with the No.2 coating; One deck at least of the degradable high polymer material layer of sandwich of layers both sides replaces with the No.2 coating in the described No.1 coating.

Pure magnesium in described No.1 coating and the No.2 coating and magnesium alloy are Powdered, graininess, sheet, thread, banded, tubulose or whisker shape, 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 the protective atmosphere, casting, forging and pressing, extruding or shaping by stock removal, etc.The effect of melting is to obtain the high-quality melt (metal or alloy liquid) that chemical composition and field trash (as oxide inclusions), air content control levels such as (as hydrogen) meet the demands; Shaping comprises and utilizes above-mentioned directly from melt formation (as casting) or be shaped indirectly (namely first make blank such as ingot casting with above-mentioned melt, blank is handled, as forging, extruding and cutting etc.) again.

The purpose of surface dressing is to remove the burr, dirt, oxide skin of goods remained on surface or generation during processing, accumulating etc. in the material preparation method step b) of the present invention, to obtain to satisfy 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 absolute ethyl alcohol, acetone etc. directly or degreasing under outer field actions such as ultrasonic wave, alkali cleaning, pickling, washing, etc.

The main purpose of anode polarization in the material preparation method step b) of the present invention, be to realize matrix material is carried out " deactivation " and the dual processing of surperficial roughening, improving the corrosion proof while of material, for combining closely between coating/matrix established solid architecture basics.So-called " deactivation " refers to utilize the selective dissolution effect micro anode dissolving " excavating " that matrix top layer electro-chemical activity is higher of anode polarization, stays the stronger micro cathode of electrochemistry inertia.When anode polarization was handled, power supply can be selected in direct current, interchange or the pulse power.Though also can be according to conventional way, use inert materials conducts such as stainless steel, graphite or platinized platinum to electrode, and take " with the goods of the same material of homalographic for to electrode " i.e. strategy of " reciprocity bipolar ", then 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 efficient that anode polarization is handled, thereby farthest realize purpose energy-conservation, synergy.As the goods to electrode, its geometry can be identical or different with workpiece.Certainly, with the workpiece identical materials when electrode material is used, also can be different with the workpiece area to the area of electrode.Concrete technological parameter such as voltage/current amplitude, frequency and dutycycle, processing time etc. during anode polarization then can require according to the difference to treatment effect to control flexibly.Sodium chloride concentration is low excessively in the anode polarization electrolyte, even use high current density/action of high voltage long period, also can't obtain gratifying treatment effect; Excessive concentration, the improvement to treatment effect when cost of material increases there is no obvious benefit, therefore, the concentration of sodium chloride should be controlled the scope at 20.0mg/L-100.0g/L.During anode polarization, solution temperature can be controlled in 1-85 ℃; Processing time then 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.

The purpose of cathodic deposition is that the matrix surface after anode polarization prepares the prefilter layer of functional membrane bottom in the material preparation method step c) of the present invention.During cathodic deposition, both can use inert materials such as platinum, stainless steel and graphite to electrode, can use again and negative electrode (being pure magnesium or magnesium alloy) identical materials.The cathodic deposition concentration of electrolyte is crossed when low or too high, all can have a negative impact to sedimentation rate and deposition effect.Cathodic deposition electrolyte also can use the ethanol based solution of magnesium chloride, magnesium nitrate, magnesium sulfate or its mixture to replace.Cathodic deposition electrical quantity control model comprises constant current, constant voltage (permanent electrode potential), or with electrokinetic potential linear scan or the scan round in certain electrode potential interval of certain sweep speed.During cathodic deposition, electrolyte temperature should be controlled at 2-60 ℃, and other concrete technological parameter such as the selection of current density, electrode potential, sweep speed and action time etc. then require to determine according to performance indications such as deposit thickness, densityes.

The heat treated main purpose of material preparation method step d) of the present invention be to realize cathodic deposition primary product---magnesium hydroxide is to magnesian conversion, simultaneously existing rete is played certain agglomeration, thereby obtain the finer and close functional membrane bottom of structure.Magnesium hydroxide is 340 ℃ to the beginning temperature that magnesia transforms (or decomposing generation magnesia), and end temp is 490 ℃.Therefore, by in 350-550 ℃ of scope, regulating the heat treatment temperature level, just can realize that magnesium hydroxide is to the control of magnesia transforming degree.As control heat treatment temperature in the time of 350-489 ℃, and the magnesium hydroxide part transforms to magnesia, and the functional membrane bottom is made up of the mixture of magnesia and magnesium hydroxide; Heat treatment temperature is in the time of 490-550 ℃, and magnesium hydroxide all is converted into magnesia, and the functional membrane bottom only is made up of magnesia.Heat treatment can be carried out under atmospheric environment or vacuum environment by any known or commercially available technology and equipment.When carrying out under aerobic environment, heat treatment can promote the thermal oxide of goods top layer metal simultaneously to a certain extent, thereby further increases the thickness of functional membrane bottom.

After anode polarization, cathodic deposition and heat treatment finish, processing such as material preferably cleans respectively, drying, comprise running water and/or distilled water, rinsed with deionized water, hot blast or compressed air dry up or the heating furnace oven dry, or dry after the rinsings such as effumability organic solvent such as ethanol, acetone etc.Cleaning, dry purpose are to remove the non-target product that is adsorbed on surface of the work, comprise anode polarization accessory substance, anode polarization and cathodic deposition electrolyte etc., avoid the solution cross pollution and influence the subsequent treatment effect.

With 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 in the material preparation method step e) of the present invention.The organic solvent of described PLLA, PLGA can be selected in A solvent, B solvent and other any known or commercially available solvent according to qualifications according to rate of dissolution, curing mode and specific requirements such as speed and coating porosity.When being mixed with the organic solvent based sols when using, the concentration of degradable high polymer material is low excessively, and then the thick coating that obtains of single application is spent thinly, and coating efficiency is low excessively; Excessive concentration, then solution viscosity is excessive, is unfavorable for that coating and coating uniformity are poor.The concrete concentration of degradable high polymer material then can require to control according to coating speed, coating quality (as uniformity, porosity etc.).When magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture used as the wild phase of degradable high polymer material based composites, consumption was low excessively, and then modified effect is not obvious; Consumption is too high, then causes the composite coating overall performance to comprise cohesive force, obviously worsen with basal body binding force and degraded barrier propterty etc.When magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture as 1) be the suspension of liquid with the organic solvent based sols of PLLA, PLGA or its mixture; or 2) be that the solid dispersed phase of the suspension of liquid is when using with the mixture of molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA; at the 0.5%-40% that accounts for solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass, then be in order to ensure the composite coating that obtains to meet the demands with its quality control.During preparation 2# solution, control wherein that the concentration of solid dispersed phase is 0.5-45.0g/L, reason has two: one, concentration are low excessively, and then the thicknesses of layers that obtains of single application is thin excessively, and coating efficiency is low excessively; Its two, excessive concentration, then the homodisperse difficulty of solid dispersed phase strengthens and the stability of solution variation, be unfavorable for applying and film quality poor.For obtaining high-quality suspension, the dispersion of described magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP can be carried out under stirring conditions such as mechanical, ultrasonic or compressed air.When applying operation, the concrete coating number of times of every kind of coating material is then controlled according to needs such as coating structure, thickness.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 the positive correlation of coating number of times.

Technology generation such as the coating method of magnesia 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 are replaced.

It should be noted that, may there be the autoxidation film between cathodic deposition layer and the matrix in the material of the present invention, be that matrix and surrounding environment (comprise atmosphere, cleaning solution such as water, absolute ethyl alcohol, alkali wash water or pickle etc., anode polarization solution, cathodic deposition solution etc.) during contact its top layer by the rete of mainly being formed by oxide, hydroxide (as magnesia, magnesium hydroxide) or its mixture of matrix that autoxidation generated.This " autoxidation film " is most of metals and the inevitable outcome of alloy under conventional manufacturing environment (corresponding is special manufacturing environments such as vacuum with it) thereof, but because its thickness very thin (nanoscale) usually can ignore substantially to the general usage Effect on Performance of material.

Used magnesia, 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 in material of the present invention and preparation method thereof.Wherein pure magnesium and magnesium alloy are advisable with Powdered, graininess, sheet, thread, banded, tubulose or whisker shape product especially.For the stability of pure magnesium and magnesium alloy in the enhancing coating, can carry out surface modification treatment to it by known or commercially available technology before using.The OCP of pure magnesium or magnesium alloy is not higher than the OCP of pure magnesium in the matrix or magnesium alloy in control preparation method and the coating that makes, purpose is to obtain required coating and guarantees that coating ingredients is not the degraded of accelerating matrix as the cathodic component under the service state, degrades but preferably have precedence over matrix (as sacrificial anode).

No.1 coating and No.2 coated designs are more than one deck in the material of the present invention, and the composition (as: consumption of magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP or CPP of different layers (" different layers " here refers to that with 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 is identical or different, in addition, the composition of the polymer material layer of sandwich of layers both sides in the No.1 coating (kind and molecular weight thereof etc.), structure and thickness are identical or different, and its purpose all is to take full advantage of the characteristic of different materials component units to realize the successful control to material monolithic combination property especially biological degradability, biocompatibility and coating/basal body binding force, coating cohesive force etc.The concrete thickness of sandwich of layers and both sides polymer material layer thereof can be controlled according to actual needs flexibly in No.2 coating and the No.1 coating.When carrying out the preparation of No.1 coating, adhesion for the polymer material layer that strengthens sandwich of layers and its both sides, the coating of sandwich of layers should be selected in to be carried out before first floor polymer material layer solidifies fully, or suitably control the porosity of the polymer material layer of sandwich of layers both sides, or finish the back at the coating coating procedure and heat-treat with suitable standard.

PLLA and PLGA can partly or entirely replace by any other known or commercially available macromolecular material with biodegradation character in material of the present invention and preparation method thereof, as natural degradable macromolecular materials such as collagen, gelatin and shitosans, and other artificial synthesized degradable macromolecular 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 the pure magnesium of indication comprises among the present invention: 1) the magnesium metal of different purity level, 2) pure magnesium goods and 3) contain the goods of pure magnesium parts (constituent element).The indication magnesium alloy comprises among the present invention: 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) contain 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 bottom part of material of the present invention, because the thermodynamic stability of magnesia, magnesium hydroxide all is higher than atomic state magnesium, therefore the functional membrane bottom must have the degraded protective capacities to pure magnesium or magnesium alloy substrate, can be used as the physical shielding layer and protects matrix to exempt from too fast degraded to a certain extent; On the other hand, according to the Pourbaix theory, even the higher magnesium hydroxide of thermodynamic stability in magnesia and the magnesium hydroxide, its can stable existence in group water solution pH value interval also more than 11.475, and the pH value of normal body fluid is 7.40 even lower, and therefore, the functional membrane bottom can progressively be degraded under the erosion of body fluid, namely have from degradation characteristic, and its degradation rate can be regulated by degree of crystallinity, density etc.With regard to the functional membrane surface layer part of material of the present invention, wherein degradable high polymer material is because biocompatibility is good and have fluid → solid and transform and hydrophobic property, be not only desirable " binding agents " of non-block materials such as magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP, and it is good to possess cold/hot-forming property simultaneously, the characteristics of flexible and controllable such as thickness, density and degradability; Wherein magnesia, 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, magnesia, magnesium hydroxide, pure magnesium and magnesium alloy also have simultaneously 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) neutralization reaction take place, the outstanding role of its potential hazard of buffering/eliminate (as aseptic inflammation etc.).In addition, wild phase as the macromolecular material based composites, magnesia, 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 the degraded barrier propterty of coating/basal body binding force and coating largely and regulate the degradation rate of coating.Based on above-mentioned analysis; functional membrane in the material of the present invention not only has excellent biocompatibility and degraded protective (to matrix) concurrently; and self has controllable biodegradable---can be at moment such as effective effect passage of blocking corrosive medium in the environment of implantation initial stage; matrix is formed 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 are regulated and control.As under the identical prerequisite of other parameter, functional membrane thickness is more thick, and then its degraded protective capacities is more strong; The functional membrane structure is more loose, and then its degraded protective capacities is more weak; Functional membrane self constituent is got over difficult degradation, and then it is more slow 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 biologically active concurrently, and its degradation rate can be regulated and control by composition, microstructure optimization such as technology such as alloying, grain refinement.Therefore, material monolithic of the present invention has remarkable advantages---and it is ubiquitous or damage biocompatibility or mechanical integrity because putting undue emphasis on biological degradability to be expected to thoroughly eliminate current material, or damage drawbacks such as biological degradability because putting undue emphasis on the degraded protective, thereby provide desirable solution for the contradiction between the control of the utilization of degradable biomaterial biodegradation character and degradation rate.

(2) technology synergy realizes that the optimization of material prepares material preparation method of the present invention based on to different materials, fully realizing of the advantage of different technologies and cooperative effect thereof, forming technique and process for modifying surface is organic compound, especially unite and utilize anode polarization, cathodic deposition, heat treatment and organic/inorganic paint-on technique, construct coating/matrix at matrix surface, coating/be coated with interlayer in conjunction with tight, composition, structure and thickness etc. are adjustable so degraded protection and controlled from degradation characteristic, have excellent biocompatibility and bioactive multiple defense system simultaneously, for the preparation of the controlled Wholly-degradable material of bio-medical provides new thinking.Particularly, carry out anode polarization and handle in the electrolyte that contains aggressivity ion such as chlorion, nitrate ion or sulfate ion, anodic solution namely takes place with ionization in the top layer metallic atom of pure magnesium or magnesium alloy.Because the inhomogeneities of composition, microstructure etc., matrix microcell course of dissolution is inhomogeneous to carry out, anodic dissolution effect shows selectively, be the optimum solvation of micro anode district, therefore, objectively, anode polarization not only has " deactivation " effect to matrix, and have significant roughening effect, can form micro-" anchor point " in a large number, thereby be that combining closely between functional membrane bottom/matrix creates conditions.Advantages such as synthetic and coating prepares integrated technique as coating, and that the electrochemistry cathodic deposition has is non-linear, low-temperature operation and controllability are good, with low cost are one of desirable technique of material surface modifying.Cathode run can realize that the original position of matrix surface magnesium hydroxide is synthetic, and heat treatment process can realize that magnesium hydroxide is to magnesian conversion and to having the sintering of rete.The formation of functional membrane bottom internally for the matrix one deck of putting on has protecting film from degradation characteristic, externally relies on its microstructure coarse, porous to become at the bottom of the ideal basis of follow-up coating (functional membrane surface layer).When magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP independently use as coating material, there is outstanding problems such as applying difficulty, adhesion difference, and when its disperse phase (wild phase) as the sandwich of layers of organic coating or macromolecular material based composites used, the problems referred to above then were readily solved.Therefore, utilize technology provided by the invention, can realize the optimization preparation of controlled full-degradable biological material.

Description of drawings

Fig. 1 is material preparation method process chart in the embodiment;

Fig. 2 is material section structure schematic diagram in the embodiment;

Fig. 3 is material function face layer section structure schematic diagram in the embodiment;

Among the figure: the 1-matrix, 2-functional membrane bottom, 3-functional membrane surface layer, a-degradable high polymer material layer, b-magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or two or more mixture layers wherein, c-degradable high polymer material layer, d-with magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be the degradable high polymer material based composites layer of wild phase.

The specific embodiment

Below in conjunction with accompanying drawing and example concrete enforcement of the present invention is described further, but enforcement of the present invention and protection domain are not limited thereto.

As shown in Figure 1, be material preparation method process chart of the present invention.The preparation method of bio-medical material of the present invention is made of melting, shaping → anode polarization → cathodic deposition → heat treatment → coating five big key steps.The purpose 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 effect of anode polarization is to realize " deactivation " and " roughening " the dual processing to the goods matrix surface; The effect of cathodic deposition is to obtain the magnesium hydroxide product layer, i.e. the prefilter layer of functional membrane bottom; Heat treated main effect is to realize that the cathodic deposition product to the sintering of magnesian conversion and existing rete, obtains the functional membrane bottom; The effect that applies is on the one hand to construct the functional membrane surface layer on the other hand to carrying out " reinforcement " from degradation function film bottom.

As shown in Figure 2, be material section structure schematic diagram of the present invention.The controlled full-degradable biological material of the present invention is by pure magnesium or magnesium alloy substrate 1, covers matrix 1 surface and functional membrane surface layer 3 integral body of adjoining the functional membrane bottom 2 of matrix 1 and adjoining functional membrane bottom 2 are constructed and formed.

As shown in Figure 3, be the functional membrane surface layer 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 the b coating belongs to the sandwich of layers of No.1 coating.Wherein the 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.

Material therefor comprises high-purity magnesium (purity 99.9%), magnesium alloy AZ31, AZ91, WE43 and ZK60 among the embodiment.Carry out melting respectively according to material composition, be shaped, obtain test specimen.Wherein melting condition: temperature 750-760 ℃, 0.3vol%SF ₆+ 50vol%CO ₂With the Air mixing gas shield, melt temperature retention 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), 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: be blank with cylindrical ingot casting, open die forging, 400 ℃ of initial forging temperatures, 320 ℃ of final forging temperatures, forging ratio 1.87 is forged preceding 420 ℃ of insulation 2h at every turn; The hot extrusion condition: be blank with cylindrical ingot casting, 350 ℃ of extrusion temperatures, extrusion ratio 20, extruding rate 1.5m/min.Line cuts the test sample that above-mentioned test specimen obtains to be of a size of 20mm * 15mm * 2.5mm.By following standard sample is carried out surface dressing: alkali cleaning → washing → pickling → washing → silicon carbide paper polishing → washing → absolute ethyl alcohol successively from coarse to fine ultrasonic cleaning → hot blast drying → standby, wherein alkali cleaning condition: the combination solution of 40.0g/L NaOH, 10.0g/L sodium phosphate and 0.2g/L neopelex, 95 ℃, 15min; Pickling condition: the combination solution of 20.0g/L nitric acid, 50.0g/L magnesium nitrate and 50.0g/L absolute ethyl alcohol, 25 ℃, 15sec; Washing condition: running water and distilled water rinsing successively.

Embodiment 1

Be research object with permanent mold casting attitude AZ91 magnesium alloy sample.Be solvent with distilled water, preparation 20.0g/L sodium chloride solution is as anode polarization electrolyte.With the homalographic sample of identical material with connect two output ports of sinusoidal AC power supplies respectively after lead is connected, and immerse in the above-mentioned electrolyte of 25 ℃ of temperature controls, keep sample spacing 3cm, 50Hz constant current 1.0mA/cm ²Handle 30min, found that the evenly macroscopic size of the distribution in small, broken bits hole point consistent with the degree of depth of specimen surface.To wash, dried anode polarization sample and stainless steel cylinder form electrode pair, sample connects the DC power cathode, the stainless steel cylinder connects the DC positive source, immerses in the 50.0g/L magnesium chloride solution with the deionized water preparation constant current 1.5mA/cm respectively ²Handle 45min, the result generates complete, the uniform field gray rete of one deck (prefilter layer of functional membrane bottom) at specimen surface.To wash, dried cathodic deposition sample places Muffle furnace, is warming up to 450 ℃ of insulations 12 hours, cools to room temperature afterwards with the furnace, found that rete (functional membrane bottom) density obviously improves.

Be solvent with the carrene, preparation 40.0g/LPLLA solution is labeled as S ₀₁Be dispersant (liquid) with the n-butanol, add 10.0g/L magnesia (solid dispersed phase) and also stir, make suspension, be labeled as S ₀₂Homogeneous mixture (mixed volume is than 2:1) with epoxychloropropane and acetone is solvent, at first prepares 25.0g/LPLLA solution (liquid), adds 5.0g/L magnesia (solid dispersed phase) then and stirs, and obtains suspension, is labeled as S ₀₃By following standard washing, dried heat treatment sample are carried out 3 and take turns dip-coating processing: sample is immersed solution S ₀₁, take out behind the 7sec, treat after coating is solidified sample to be immersed suspension S ₀₂, take out behind the 15sec, after drying up with cold wind sample is immersed solution S ₀₁, take out behind the 3sec, treating that coating is solidified immerses solution S with sample ₀₃, take out behind the 10sec, treat after the coating spontaneous curing sample to be immersed solution S ₀₁, take out behind the 7sec, treat coating curing.The result obtains uniform composite coating (functional membrane surface layer) at the heat treatment specimen surface, and this coating is by 1) be the PLLA coating and 2 of sandwich of layers with magnesia) be that the PLLA coating of sandwich of layers is formed by stacking successively with magnesia/PLLA composite.

With the SBF(simulated body fluid) be tested media (its composition and human plasma chemical composition contrast situation see Table 1), control appearance face is than (ratio that the 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 the test of external biological degradation property respectively to said sample.The result shows: sample matrix behind about 42d just begins to occur macroscopic erosion trace, compare and namely begin the result of corroding after blank sample (namely only surface dressing and do not carry out the sample of anode polarization, cathodic deposition, heat treatment 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 is basic complete obiteration behind about 97d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 182d, shows that material monolithic has high-fall solution characteristic.

Embodiment 2

Be research object with the high-purity magnesium sample of permanent mold casting attitude.Except sodium chloride concentration is changed into the 100.0g/L, other condition control of anode polarization found that with embodiment 1: except single pit area increases, outside pit density and distributing homogeneity thereof reduced, other was with embodiment 1.Except density of magnesium chloride is changed into the 0.5g/L, other condition control of cathodic deposition and result are with embodiment 1.Except temperature being changed into 350 ℃, the time changes into outside the 24h, and other condition control of heat treatment and result are with embodiment 1.Be solvent with the chloroform, at first prepare totally four parts of 30.0g/LPLLA solution, add 10.0g/L magnesium hydroxide, pure magnesium powder (sphere, meta particle diameter d then respectively ₅₀=47 μ m), β-TCP and CPP, stir, obtain suspension, be labeled as solution S respectively ₀₄, S ₀₅, S ₀₆And S ₀₇By following standard washing, dried heat treatment sample are carried out 2 and take turns dip-coating processing: sample is immersed solution S ₀₄In, take out behind the 15sec, treat after coating is solidified sample to be immersed solution S ₀₅, take out behind the 15sec, treat after coating is solidified sample to be immersed solution S ₀₆, take out behind the 15sec, treat after coating is solidified sample to be immersed solution S ₀₇, treat coating curing.The result obtains uniform composite coating (functional membrane surface layer) at specimen surface, and this coating is by being that the PLLA matrix composite coating of wild phase is formed by stacking successively with magnesium hydroxide, pure magnesium, β-TCP and CPP respectively.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 39d just begins to occur macroscopic erosion trace, shows that functional membrane has good biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 87d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 250d, shows that material monolithic has high-fall solution characteristic.

Embodiment 3

Be research object with permanent mold casting attitude AZ31 magnesium alloy sample.Except sodium chloride concentration is changed into the 20.0mg/L, other condition control of anode polarization found that with embodiment 1: except pit density and degree of depth reduction, treatment effect is with embodiment 1.Except density of magnesium chloride is changed into the 150.0g/L, other condition control of cathodic deposition and result are with embodiment 1.Except temperature being changed into 550 ℃, the time changes into outside the 1h, and other condition control of heat treatment and result are with embodiment 1.Be solvent with the chloroform, preparation 75.0g/LPLLA solution is labeled as solution S ₀₈Be dispersant (liquid) with ethanol, add 0.5g/L magnesium hydroxide (solid dispersed phase), the acquisition suspension that stirs is labeled as solution S ₀₉Be solvent with the carrene, at first prepare 75.0g/LPLLA solution, add 0.377g/L magnesia then and stir, obtain suspension, be labeled as solution S ₁₀By following standard washing, dried heat treatment sample are carried out dip-coating processing: sample is immersed solution S ₀₈, take out behind the 7sec, treat after coating is solidified sample to be immersed solution S ₀₉, take out behind the 30sec, treat after the coating drying sample to be immersed solution S ₀₈, take out behind the 7sec, treat after coating is solidified sample to be immersed solution S ₁₀, take out behind the 20sec, treat coating curing.The result obtains uniformly by 1 at specimen surface) be the PLLA coating and 2 of sandwich of layers with the magnesium hydroxide) composite coating (functional membrane surface layer) that magnesia/the PLLA composite coating is formed by stacking.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 21d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 45d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 102d, shows that material monolithic has high-fall solution characteristic.

Embodiment 4

Be research object with permanent mold casting attitude ZK60 magnesium alloy sample.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.Except the concentration with PLLA changes the 0.2g/L solution S into ₀₈Preparation with embodiment 3.Except the concentration with magnesium hydroxide changes the 45.0g/L solution S into ₀₉Preparation with embodiment 3.Except the concentration with PLLA changes 0.2g/L into, magnesian concentration changes into outside the 0.133g/L, solution S ₁₀Preparation with embodiment 3.Carry out dip-coating processing with 3 pairs of washings of embodiment, dried heat treatment sample, the result is with embodiment 3.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 17d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 30d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 77d, shows that material monolithic has high-fall solution characteristic.

Embodiment 5

Be research object with permanent mold casting attitude WE43 magnesium alloy sample.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.Solution S ₀₁Preparation with embodiment 1.Be dispersant (liquid) with acetone, add 10.0g/L magnesium hydroxide, pure magnesium powder (sphere, meta particle diameter d respectively ₅₀=47 μ m), β-TCP and CPP, stir, obtain suspension, be labeled as solution S respectively ₁₁, S ₁₂, S ₁₃And S ₁₄By following standard washing, dried heat treatment sample are carried out dip-coating processing: sample is immersed solution S ₀₁, take out behind the 10sec, treat after coating is solidified sample to be immersed solution S ₁₁, take out behind the 35sec, treat after the coating drying sample to be immersed solution S ₀₁, take out behind the 10sec, treat after coating is solidified sample to be immersed solution S ₁₂, take out behind the 35sec, treat after the coating drying sample to be immersed solution S ₀₁, take out behind the 10sec, treat after coating is solidified sample to be immersed solution S ₁₃, take out behind the 35sec, treat after the coating drying sample to be immersed solution S ₀₁, take out behind the 10sec, treat after coating is solidified sample to be immersed solution S ₁₄, take out behind the 35sec, treat after the coating drying sample to be immersed solution S ₀₁, take out behind the 10sec, treat coating curing.It is the composite coating (functional membrane surface layer) that the PLLA coating of sandwich of layers superposes successively that the result obtains respectively with magnesium hydroxide, pure magnesium, β-TCP and CPP.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 26d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 50d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 125d, shows that material monolithic has high-fall solution characteristic.

Embodiment 6

Be research object to forge attitude WE43 magnesium alloy sample.Except the sodium chloride in the electrolyte is changed into respectively sodium nitrate, sodium sulphate, lithium chloride, lithium nitrate, lithium sulfate, potassium chloride, potassium nitrate, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate or the magnesium sulfate, other condition control of anode polarization and result are with embodiment 1.Except the magnesium chloride in the electrolyte is changed into respectively magnesium nitrate or the magnesium sulfate, other condition control of cathodic deposition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 1.Carry out solution S with embodiment 1 ₀₃Preparation.With this solution to through washing, dried heat treatment sample brushes respectively, spin coating and spray treatment, the acquisition surface density is 1.72mg/cm ²Uniform magnesia/PLLA composite coating (functional membrane surface layer).Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 44d just begins to occur macroscopic erosion trace, shows that functional membrane has good biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 89d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 182d, shows that material monolithic has high-fall solution characteristic.

Embodiment 7

Be research object with die casting attitude AZ31 magnesium alloy sample.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.Carry out solution S with embodiment 1 ₀₂Preparation.The PLLA solid particle is heated to complete molten condition and 210 ℃ of insulations, is labeled as solution S ₁₅By following standard washing, dried heat treatment sample are carried out dip-coating processing: sample is immersed solution S ₁₅, take out behind the 30sec, treat after coating is solidified sample to be immersed solution S ₀₂, take out behind the 15sec, treat after the coating drying sample to be immersed solution S ₁₅, take out behind the 2sec, treat coating curing.It is the PLLA coating (functional membrane surface layer) of sandwich of layers with magnesia uniformly that the result obtains at specimen surface.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 15d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 27d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 130d, shows that material monolithic has high-fall solution characteristic.

Embodiment 8

Be research object with extruding attitude AZ31 magnesium alloy sample.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.The 190.0gPLLA solid particle is heated to complete molten condition and 210 ℃ of insulations, adds the mixture of 5.0g magnesia and 5.0g magnesium hydroxide, the back that stirs obtains suspension, is labeled as solution S ₁₆By following standard washing, dried heat treatment sample are carried out dip-coating processing: sample is immersed solution S ₁₆, take out behind the 45sec, treat after coating is solidified sample to be immersed solution S ₁₆, take out behind the 3sec, treat coating curing.It is the PLLA matrix composite coating of wild phase with magnesia and magnesium hydroxide uniformly that the result obtains at specimen surface.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 23d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 42d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 157d, shows that material monolithic has high-fall solution characteristic.

Embodiment 9

Be research object with die casting attitude AZ91 magnesium alloy sample.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.Carry out solution S with embodiment 1 ₀₁, S ₀₂And S ₀₃Preparation.By following standard washing, dried heat treatment sample are carried out dip-coating processing: sample is immersed solution S ₀₃, take out behind the 60sec, treat after coating is solidified sample to be immersed solution S ₀₂, take out behind the 15sec, treat after the coating drying sample to be immersed solution S ₀₃, take out behind the 20sec, treat after coating is solidified sample to be immersed solution S ₀₂, take out behind the 15sec, sample is immersed solution S ₀₁, take out behind the 30sec, treat coating curing.The result obtains composite coating (functional membrane surface layer) at the cathodic deposition specimen surface, this coating is by 1) be the magnesia/PLLA composite coating of sandwich of layers with magnesia, with 2) be sandwich of layers with magnesia, the coating that both sides are respectively magnesia/PLLA composite coating and PLLA coating is formed by stacking.Carrying out the outer biological degradability of material bodies with embodiment 1 can test, and the result shows: sample matrix behind about 10d just begins to occur macroscopic erosion trace, shows that functional membrane has certain biodegradation protective capacities to matrix; Functional membrane is basic complete obiteration behind about 23d, and it is good in degradation characteristic to show that it has; Sample is degraded fully behind about 140d, shows that material monolithic has high-fall solution characteristic.

With further reference to medicine equipment biological assessment ISO 10993 standards, with the negative contrast of widely used titanium alloy ti6al4v on the clinical medicine, it is the bio-compatible property testing of representative that each sample among the embodiment 1-embodiment 9 is carried out respectively with hemolysis rate and vitro cytotoxicity, and the result shows: each sample all shows the excellent biological compatibility suitable with Ti6Al4V.

Table 1: tested media and the contrast of human plasma chemical composition

Claims (9)

1. the preparation method of a bio-medical material is characterized in that comprising following key step:

A) melting and shaping: the pure magnesium of melting or magnesium alloy, and form manufacturing, obtain the goods matrix;

B) anode polarization: step a) resulting product matrix is immersed behind surface dressing in the group water solution of sodium chloride that concentration is 20.0mg/L-100.0g/L, is to electrode with the goods of the same material of homalographic, and energising is handled;

C) cathodic deposition: will immerse in the group water solution of magnesium chloride that concentration be 0.5-150.0g/L through goods matrix that step b) was handled, energising is handled, and obtains to have concurrently the degraded protection and from the prefilter layer of the functional membrane bottom of degradation characteristic;

D) heat treatment: the goods matrix of handling through step c) is heat-treated, obtain to have concurrently the degraded protection and from the functional membrane bottom of degradation characteristic, wherein said heat treatment temperature is 350-550 ℃, temperature retention time is 1-24h;

E) apply: comprise following key step:

E-1) preparation of solution:

1# solution: be the poly-left lactic acid of PLLA(), PLGA(polylactic acid-glycolic guanidine-acetic acid) or the organic solvent based sols of its mixture, its concentration is 0.2-75.0g/L;

2# solution: for magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP(bata-tricalcium phosphate), CPP(calcium polyphosphate) or wherein two or more mixtures are solid dispersed phase, with water, acetone, ethanol, n-butanol or wherein two or more mixtures be the suspension of liquid, the concentration of wherein said solid dispersed phase is 0.5-45.0g/L;

3# solution: for magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be solid dispersed phase, organic solvent based sols with PLLA, PLGA or its mixture is the suspension of 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;

E-2) coating of coating: the goods matrix of handling through step d) is carried out coating processing, obtain to have concurrently the degraded protection and from the functional membrane surface layer of degradation characteristic, described coating processing adopts in following three kinds of schemes more than one to carry out:

Scheme one: unite and use e-1) step is joined 1# solution and 2# solution, follows elder generation with the order of using 1# solution behind the 1# solution with 2# solution again, carries out taking turns above coating;

Scheme two: the independent e-1 that uses) step is joined 3# solution and is carried out taking turns above coating;

Scheme three: unite and use e-1) step is joined 1# solution, 2# solution and 3# solution, follows elder generation with the order of using 3# solution behind the 1# solution with 2# solution again, carries out taking turns above coating.

2. the preparation method of bio-medical material according to claim 1 is characterized in that: sodium chloride described in the step b) with sodium nitrate, sodium sulphate, 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 mixtures partly or entirely replace; Magnesium chloride described in the step c) partly or entirely replaces with magnesium nitrate, magnesium sulfate or its mixture.

3. the preparation method of bio-medical material according to claim 1, it is characterized in that: the organic solvent of the solution of 1# step e-1) and 3# solution is a kind of in A solvent and the B solvent, wherein the A solvent is more than one in epoxychloropropane, carrene or the chloroform, the B solvent be the A solvent with acetone, ethanol or n-butanol in more than one mixtures that obtain after evenly mixing; Step e-1) the pure magnesium in the solution of 2# described in and the 3# solution and magnesium alloy are Powdered, graininess, sheet, thread, banded, tubulose or whisker shape, and its OCP in any equivalent environment medium is not higher than the OCP of pure magnesium in the goods matrix or magnesium alloy.

4. the preparation method of bio-medical material according to claim 1 is characterized in that: the mixture replacement of the solution of 1# step e-1) molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA; Step e-1) solution of 3# described in order to magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be solid dispersed phase, mixture with molten state PLLA, molten state PLGA or molten state PLLA and molten state PLGA is the suspension replacement of liquid, 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 material according to claim 1 is characterized in that: a kind of 3# of using solution replacement of scheme one described 1# solution and 2# solution step e-2); Step e-2) painting method described in comprises dip-coating, brushing, spin coating or spraying.

6. the preparation method of bio-medical material according to claim 1 is characterized in that: contain the coating of PLLA or PLGA when coating after, carry out spontaneous curing or artificial curing handled, after treating this coating layer portion or solidifying fully, carry out the coating of follow-up coating again; When applying magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein behind the two or more mixtures, carrying out drying processing.

7. bio-medical material that is made by the described preparation method of claim 1, it is characterized in that comprising pure magnesium or magnesium alloy substrate and cover matrix surface have the degraded protection concurrently and from the functional membrane of degradation characteristic, wherein functional membrane comprises bottom and surface layer; Described bottom mainly is made up of the mixture of magnesia or magnesia and magnesium hydroxide; Described surface layer comprises in No.1 coating and the No.2 coating at least a; Described No.1 coating for magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be the degradable high polymer material layer of sandwich of layers; Described No.2 coating for magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein two or more mixtures be the degradable high polymer material based composites layer of wild phase, 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 the No.2 coating is PLLA, PLGA or its mixture.

8. bio-medical material according to claim 7, it is characterized in that: described No.1 coating and No.2 coating are respectively more than one deck, and the composition of different layers, structure and thickness are identical or different; Composition, structure and the thickness of the degradable high polymer material layer of sandwich of layers both sides are identical or different in the described No.1 coating; Sandwich of layers in the described No.1 coating replaces with the No.2 coating; One deck at least of the degradable high polymer material layer of sandwich of layers both sides replaces with the No.2 coating in the described No.1 coating.

9. bio-medical material according to claim 7, it is characterized in that: the pure magnesium in described No.1 coating and the No.2 coating and magnesium alloy are Powdered, graininess, sheet, thread, banded, tubulose or whisker shape, 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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