CN103286053B - 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 manufacture thereof and applied technical field, particularly relate to a kind of bio-medical 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 self medical treatment & health cause.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 calamity etc., the haze causing disease and wound to become the mankind forever can't get rid of.As the important means of modern medicine---the important foundation of medicine equipment and part, biomaterial is used for the Diagnosis and Treat of disease, the reparation of histoorgan, replacement or function to be promoted, and a large amount of struggle is rehabilitated in the sufferer at 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 21 century very active new source of economic growth.For China, China's Medical Device Market speedup in 2010 is up to 23%, and market scale breaks through 1 first, and 00,000,000,000 yuan of high pointes become the second-biggest-in-the-world Medical Device Market being only second to the U.S., and expecting market scale in 2015 will close to 3,40,000,000,000 yuan.Just because of the so huge society of biomaterial and economic worth, its R&D work is subject to countries in the world government, the showing great attention to of 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, 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 the load embedded material that current clinical medicine is especially most widely used in orthopaedics (as backbone correcting, knochenbruch joint, skull repairing etc.).But existing medical metal material such as the 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.To obtain the titanium alloy of extensive use at present at clinical medicine, its main performance defect comprises: (1) does not mate due to elastic modelling quantity, cause by the dynamic changes process obstacle of implant to adjacent bone tissue, namely " stress shielding " effect is produced, make its risk as implants (as suppressed knitting, cause osteoporosis, bone information or osteanabrosis, even occur secondary fracture etc.) cannot evade all the time; (2) degraded of pure titanium in body can cause allergy even dead, Al and V in typical titanium alloy ti6al4v all has cytotoxicity, and wherein V can cause chronic inflammation, and Al is combined with Phos, also can bring out senile dementia while causing scarce phosphorus; (3) because biological degradability is poor, after damaged tissues/organ completes reconstruction, implant must take out through second operation, has therefore blocked the rehabilitation process of patient, adds additional its body and mind misery and financial burden.For these reasons, under the prerequisite ensureing security, find the better new material of combination property, new technology, be emphasis and the focus place of biomaterial research always.Just 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.

Magnesium alloy uses the inherent advantage with a series of uniqueness 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 by progressively biodegradation to finally disappearing completely, overcome the complication that metal body longer-term persistence in human body causes, make patient from second operation Kucheng for may, mean simultaneously and repeatedly can get involved intervention at same diseased region.(2) bio-compatible sexual clorminance.Magnesium is the non-dissident's composition of human body, is one of human body macroelement (Mg ²⁺be only second to Na in human body ⁺, 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 maintenance of life, health, formed at biogenic apatite, bone matrix changes, osteocyte is formed and combine, knitting, and the normal performance aspect of the function such as nerve, muscle, heart all plays very important role.Therefore, 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 close with the corresponding parameter (10-40GPa) of skeleton, is conducive to reducing even eliminating 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, magnesium has excellent osteoinductive.(5) traditional performance advantage.Magnesium has " one is low " (density is low), " two is high " (specific strength, specific stiffness is high), " three is good " (casting and machinability, dimensional stability and recyclable property good) and " top four " (electromagnetic shielding capability, damping noise reduction ability and heat conduction, conductive capability is strong) feature, therefore the good reputation of " 21 century green engineering material " is enjoyed, in various fields especially in " lightweight ", " environmental protection " etc. are significant or have 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 in the world as the Application and Development of structural material shows great attention to.(6) resource and price advantage.On the earth, magnesium resource is very abundant, magnesium relative amount 10.63% in earth's crust metallic element, and being only second to aluminium (31.51%) and the 3rd, iron (22.02%) residence, is 4.37 times of Ti content (2.43%).Wherein only just there is magnesium---the magnesium density 1.1kg/m of " inexhaustible " in seawater ³, total content is up to 2.1 × 10 ¹⁵ton.Developing rapidly of rich in natural resources and the technology such as smelting, shaping, causes the price of magnesium metal and goods thereof to seem very cheap relative to titanium etc.For raw material, latest domestic market quotes statistics shows, at present, the average price (about 17.0 yuan/kg) of 99.95% primary magnesium ingot is only (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, 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 regrettably, magnesium self thermodynamic stability difference (E ⁰=-2.37V NHE), surface autoxidation film thin (~ 10nm) and loosen (because of PBR=0.80) and without " self-healing " ability, effective protection can not be provided 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 does not only benefit from the biodegradation character of its uniqueness, on the contrary, but lock into the too fast series of problems brought of degraded always, as: a) the too early decay of material product military service performance especially mechanical integrity was even lost efficacy, b) biocompatibility is endangered, c) heavy dose has the rapid release of the alloying element of potential source biomolecule toxicity, d) host's magnesium Metabolic stress is increased, even cause hypermagnesemia, e) local ph is caused sharply to rise, and f) local organization pneumatosis, etc.For these reasons, 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 regulate as required) while, the biocompatibility improving material even gives its biologically active, to meet the rigors 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 based on the Magnesium and magnesium alloys based composites technology of preparing of surface modification obtains great success.Relate to major surfaces modification technology to comprise: (1) conventional differential arc oxidation (MAO) technology (refer to nondegradation or almost without the MAO ceramic membrane of degradation capability for preparing the MAO technology of object, lower same), (2) based on the complex technique of 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 obtained composite thereof, but also there is major defect: or the improvement of the suppression be absorbed in matrix biological degradability and biocompatibility, not only do not consider surface reforming layer " retiring from political life after winning tremendous successes " after damaged tissues/organ completes reconstruction---biodegradation problem, on the contrary, for improving modified effect, but thinking is made an effort in synthesis/applying compactness, nondegradation modified layer routinely; Although or with respect to the biological degradability of modified layer, comprehensive usage performance is unsatisfactory.With regard to the former, with utilize composite realizes to the MAO process of matrix be prepared as example, owing to adopting conventional electrolysis liquid (as silicate, phosphate and fluoride-based electrolyte), therefore 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 contravention.In other words, when using as intravascular stent etc. as " exempting from second operation " implantation instrument or tubulose/cavity-like tissue/organ timbering material, even if environment lower substrate progressively can degrade, absorb according to expection under arms, nondegradation housing surface modification retes such as () MAO films or its peel off the long-term existence of fragment, also by making all effort of the permanent external source precursor reactant of release body, all that has been achieved is spoiled, even bringing on a disaster property consequence (as artery-clogging).With regard to the latter, example is prepared as in order to what be used in that matrix surface coating degradable high polymer material realizes composite, there is following subject matter: (1) does not consider the potential hazard of macromolecular material acid degradation products, as a. causes the acidifying of local physiological environment then to cause aseptic inflammation, b. accelerate the degraded of magnesium alloy substrate, therefore have no proposition and tackle/protection measure targetedly; (2) macromolecular material isolated use or only with nondegradation HA(hydroxyapatite) compound use, limit 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 outstanding problem for existing in existing bio-medical material and 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 preparation method for bio-medical material, it comprises following key step:

A) melting and shaping: the pure magnesium of melting or magnesium alloy, and carry out figuration manufacture, obtain article substrate;

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

C) cathodic deposition: it is in the group water solution of the magnesium chloride of 0.5-150.0g/L that the article substrate through step b) process is immersed concentration, and energising processes, obtains the prefilter layer having degraded protection and the functional membrane bottom from degradation characteristic concurrently;

D) heat treatment: the article substrate through step c) process is heat-treated, obtain and have degraded protection and the functional membrane bottom from degradation characteristic concurrently, wherein said heat treatment temperature is 350-550 DEG C, and 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 mixture for solid dispersed phase, with water, acetone, ethanol, n-butanol or the wherein two or more mixture suspension that is 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 mixture for solid dispersed phase, with the suspension that the organic solvent based sols of PLLA, PLGA or its mixture 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;

E-2) coating of coating: carry out coating processing to the article substrate through step d) process, obtains and has degraded protection and the functional membrane surface layer from degradation characteristic concurrently, and more than one in the following three kinds of schemes of described coating processing employing carry out:

Scheme one: conbined usage e-1) step joins 1# solution and 2# solution, and follow first by the order using 1# solution after 1# solution with 2# solution again, carry out taking turns above coating;

Scheme two: independently use e-1) step joins 3# solution and carries out taking turns above coating;

Scheme three: conbined usage e-1) step joins 1# solution, 2# solution and 3# solution, and follow first by the order using 3# solution after 1# solution with 2# solution again, carry out taking turns above coating.

The sodium nitrate of sodium chloride described in step b), 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 mixture partly or entirely replace; The magnesium nitrate of magnesium chloride described in step c), magnesium sulfate or its mixture partly or entirely replace.

Step e-1) described in the organic solvent of 1# solution and 3# solution be one in A solvent and B solvent, wherein A solvent is more than one in epoxychloropropane, carrene or chloroform, and B solvent is the mixture obtained after more than one Homogeneous phase mixing in A solvent and acetone, ethanol or n-butanol; Step e-1) described in pure Magnesium and magnesium alloys in 2# solution and 3# solution be Powdered, graininess, sheet, thread, banded, tubulose or crystal whisker-shaped, and its OCP in any equivalent environment medium not higher than article substrate in the OCP of pure magnesium or magnesium alloy.

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

After coating is containing the coating of PLLA or PLGA, carries out spontaneous curing or manually solidify process, until this coating layer portion or after solidifying completely, then carrying out the coating of follow-up coating; As coating magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein after two or more mixture, carry out drying and process.

The bio-medical material obtained by above-mentioned preparation method, what it comprised pure magnesium or magnesium alloy substrate and covered matrix surface has degraded protection and the functional membrane from degradation characteristic concurrently, and wherein functional membrane comprises bottom and surface layer; Described bottom forms primarily of the mixture of magnesia or magnesia and magnesium hydroxide; Described surface layer comprises at least one in No.1 coating and No.2 coating; Described No.1 coating is with magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or the wherein two or more mixture degradable high polymer material layer that is sandwich of layers; Described No.2 coating is that the quality of wherein said wild phase accounts for the 0.5%-40% of composite quality with magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or the wherein two or more mixture degradable high polymer material based composites layer that is wild phase; Degradable high polymer material in described No.1 coating and 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; In described No.1 coating, the composition of the degradable high polymer material layer of sandwich of layers both sides, structure and thickness are identical or different; Sandwich of layers No.2 coating in described No.1 coating replaces; In described No.1 coating, at least one deck No.2 coating of the degradable high polymer material layer of sandwich of layers both sides replaces.

Pure Magnesium and magnesium alloys in described No.1 coating and No.2 coating is Powdered, graininess, sheet, 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.

Melting and the shaping of material preparation method step a) of the present invention 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 the high-quality melt (metal or alloy liquid) that acquisition chemical composition and the level of control such as 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 (namely first obtain blank as ingot casting with above-mentioned melt, then process blank, as forging, extrude and cutting etc.).

In material preparation method step b) of the present invention, the object of surface dressing is the burr, dirt, oxide skin etc. of removing goods remained on surface or generation during processing, accumulating, to obtain the surface quality meeting subsequent treatment and require.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 the outer field actions such as ultrasonic wave, alkali cleaning, pickling, washing, etc.

The main purpose that material preparation method step b) of the present invention is anodized, be to realize carrying out " deactivation " and surface roughening Duplex treatment to matrix material, improve material corrosion proof while, for combining closely between coating/matrix establishes solid architecture basics.So-called " deactivation ", refers to and utilizes the selective dissolution effect of anode polarization that micro anode higher for matrix skin electro-chemical activity is dissolved " excavating ", leave the micro cathode that electrochemicaUy inert is stronger.During anode polarization process, power supply can be selected in direct current, interchange or the pulse power.Although also can conveniently way, use the inert material such as stainless steel, graphite or platinized platinum as to electrode, and take " be to electrode with the goods of the same material of homalographic " the i.e. strategy of " equity is bipolar ", then both can avoid the heterogeneous contamination hazard potential to electrode pair electrolyte, again can 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 of anode polarization process, thus farthest realize object that is energy-conservation, synergy.As the goods to electrode, its geometry can be identical or different with workpiece.Certainly, using the material identical with workpiece as when using electrode material, also can be different from workpiece area to the area of electrode.Voltage/current amplitude, frequency and the concrete technology parameter such as dutycycle, processing time thereof during anode polarization, then can require to control flexibly according to the difference for the treatment of 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 while increasing, and 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 DEG C; Processing time then can according to the size applying electrical quantity, the height of electrolyte concentration, and the specific requirement etc. of surface roughening degree controls flexibly.

In material preparation method step c) of the present invention, the object of cathodic deposition is that the matrix surface after anode polarization prepares the prefilter layer of functional membrane bottom.During cathodic deposition, both can use the inert materials such as platinum, stainless steel and graphite to electrode, again can with the material identical with negative electrode (i.e. pure magnesium or magnesium alloy).Cathodic deposition concentration of electrolyte too low or too high time, all can have a negative impact to sedimentation rate and deposition effect.Cathodic deposition electrolyte also can use the alcoholic base solutions 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 control at 2-60 DEG C, and other concrete technology parameter as the selection of current density, electrode potential, sweep speed and action time etc., then requires to determine according to the performance indications such as deposit thickness, density.

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

After anode polarization, cathodic deposition and heat treatment terminate, material preferably carries out process such as cleaning, dry respectively, comprise running 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 is as dried after the rinsing such as ethanol, acetone.Cleaning, dry object are to remove the non-targeted product being adsorbed on surface of the work, comprise anode polarization accessory substance, anode polarization and cathodic deposition electrolyte etc., avoid solution cross pollution and affect subsequent treatment effect.

By the main purpose of various coating material liquefaction (being mixed with solution or fusing use) in material preparation method step e) of the present invention, be conveniently to apply and guarantee to obtain homogeneous coating effect.The organic solvent of described PLLA, PLGA can according to rate of dissolution, curing mode and the specific requirement such as speed and coating porosity, optimum selecting in A solvent, B solvent and other any known or commercially available solvent.When being mixed with organic solvent based sols and using, the concentration of degradable high polymer material is too low, then the thick coating that single application obtains is spent thin, and coating efficiency is too low; Excessive concentration, then solution viscosity is excessive, be unfavorable for coating and coating uniformity is 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 as degradable high polymer material based composites wild phase use time, consumption is too low, then modified effect is not obvious; Consumption is too high, then cause composite coating overall performance to comprise cohesive force, obviously worsen with basal body binding force and barrier propterty etc. of degrading.When magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture are as 1) suspension that is liquid with the organic solvent based sols of PLLA, PLGA or its mixture; or 2) when using with the solid dispersed phase of the mixture of molten state PLLA, molten state PLGA or molten state PLLA and the molten state PLGA suspension that is liquid; by its quality control at the 0.5%-40% accounting for solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture gross mass, be then in order to ensure obtaining the composite coating met the demands.During preparation 2# solution, the concentration controlling wherein solid dispersed phase is 0.5-45.0g/L, and reason has two: one, and concentration is too low, then the thicknesses of layers of single application acquisition is excessively thin, and coating efficiency is too low; Its two, excessive concentration, then the homodisperse difficulty of solid dispersed phase strengthens and stability of solution is deteriorated, and is unfavorable for coating and film quality is 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 the stirring conditions such as mechanical, ultrasonic or compressed air.During coating operation, the concrete coating number of times of often kind of coating material then needs to control according to coating structure, thickness etc.When using identical coating material repeatedly to apply, the solution that each coating uses can be identical, also can be different.For identical coating solution, coating layer thickness and the positive correlation of coating number of times of acquisition.

The coating method of magnesia of the present invention, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or its mixture can the technology such as electrophoretic deposition, magnetron sputtering or ion beam assisted depositing replace.

It should be noted that, autoxidation film may be there is between cathodic deposition layer and matrix in material of the present invention, namely matrix and surrounding environment (comprise air, cleaning solution is as water, absolute ethyl alcohol, alkali wash water or pickle etc., anode polarization solution, cathodic deposition solution etc.) contact time its top layer the rete of the oxide primarily of matrix, hydroxide (as magnesia, magnesium hydroxide) or its mixture composition that generates by autoxidation.This " autoxidation film " is most metals and the inevitable outcome of alloy under conventional manufacturing environment (what correspond is the special manufacturing environments such as vacuum) thereof, but because its thickness usual very thin (nanoscale), substantially negligible on the impact of material general usage performance.

Magnesia used in material of the present invention and preparation method thereof, 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, sheet, thread, banded, tubulose or crystal whisker-shaped product especially.For strengthening the stability of pure Magnesium and magnesium alloys in coating, before using, surface modification treatment can be carried out by known or commercially available technology to it.The OCP controlling pure magnesium or magnesium alloy in preparation method and obtained coating is not higher than the OCP of magnesium pure in matrix or magnesium alloy, coating needed for object is to obtain and under guaranteeing service state coating ingredients be not accelerate the degraded of matrix as cathodic component, but preferably have precedence over matrix (as sacrificial anode) and degrade.

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 magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP or CPP of different layers (" different layers " here refers to No.1 coating or No.2 coating is 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, in No.1 coating, the composition (kind and molecular weight etc. thereof) of the polymer material layer of sandwich of layers both sides, structure and thickness are identical or different, and the characteristic that its object is all to make 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 cohesive force 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 the suitable porosity controlling the polymer material layer of sandwich of layers both sides, or heat-treat with suitable specification after coating application procedures terminates.

In material of the present invention and preparation method thereof, PLLA and PLGA can partly or entirely replace by other known or commercially available macromolecular material with biodegradation character any, as natural degradable macromolecular materials such as collagen, gelatin and shitosans, and other the absorbable macromolecule material.β-TCP and CPP also can partly or entirely replace by other known or commercially available degradable inorganic bio any.

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 levels, 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 in following two:

(1) material integrates ideal characterisitics with regard to the functional membrane floor portions of material of the present invention, because the thermodynamic stability of magnesia, magnesium hydroxide is all higher than atomic state magnesium, therefore functional membrane bottom must have degraded protective capacities to pure magnesium or magnesium alloy substrate, can be used as physical shielding layer and protects matrix to exempt from too fast degraded to a certain extent; On the other hand, theoretical according to Pourbaix, even the magnesium hydroxide that in magnesia and magnesium hydroxide, thermodynamic stability is higher, its in group water solution can the pH value interval of stable existence also more than 11.475, and the pH value of normal body fluid is 7.40 even lower, therefore, functional membrane bottom can progressively be degraded under the erosion of body fluid, namely have from degradation characteristic, and its degradation rate regulates by degree of crystallinity, density etc.With regard to the functional membrane facing sections of material of the present invention, wherein degradable high polymer material due to biocompatibility excellent and there is fluid → solid conversion and hydrophobic property, be not only " binding agent " that the non-block materials such as magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP are desirable, and it is good to possess cold/hot-forming property simultaneously, the feature that thickness, density and degradability etc. are controlled flexibly; 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 alloys also have simultaneously, with the acid degradation products of degradable high polymer material (the intermediate product lactic acid of degrading as PLLA and end product carbon dioxide and water), neutralization reaction occur, and cushion/eliminate the outstanding role of its potential hazard (as aseptic inflammation etc.).In addition, as the wild phase of 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 material of the present invention not only has excellent biocompatibility and degraded protective (to matrix) concurrently, and self has controllable biodegradable---can in moment as the implantation initial stage effectively blocks the action passage of corrosive medium in environment, tight protection (degraded protection) is formed to matrix, self can degrade gradually along with the reconstruction of damaged tissues/organ again (from degraded), final exposure matrix 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, then its degraded protective capacities is stronger; Functional membrane structure is more loose, then its degraded protective capacities is more weak; Functional membrane self constituent gets over difficult degradation, then 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 biologically active concurrently, and its degradation rate regulates and controls by composition, microstructure optimization such as the technology such as alloying, grain refinement.Therefore, material monolithic of the present invention has obvious advantage---be expected to thoroughly to eliminate current material ubiquitous or damage biocompatibility or mechanical integrity because putting undue emphasis on biological degradability, or because putting undue emphasis on degraded protective and damage the drawbacks such as biological degradability, thus for degradable biomaterial biodegradation character utilize and degradation rate control between contradiction desirable solution is provided.

(2) the technology synergy optimized fabrication material preparation method of the present invention that realizes material is based on to different materials, the advantage of different technologies and fully realizing of cooperative effect thereof, by forming technique and process for modifying surface organic composite, especially combine and utilize anode polarization, cathodic deposition, heat treatment and organic/inorganic paint-on technique, coating/matrix is constructed at matrix surface, coating/painting Coating combination is tight, composition, structure and thickness etc. are adjustable therefore degraded protection and controlled from degradation characteristic, there is superior bio compatibility and bioactive multiple defense system simultaneously, preparation for biological medical controllable all-degradable material provides new thinking.Specifically, containing erosion carbon dioxide as the electrolyte of chlorion, nitrate ion or sulfate ion in carry out anode polarization process, by ionization, namely there is anodic solution in the coating metal atom of pure magnesium or magnesium alloy.Due to the inhomogeneities of composition, microstructure etc., matrix microcell course of dissolution is uneven to carry out, anodic dissolution effect shows selective, i.e. micro anode district optimum solvation, therefore, objectively, anode polarization not only has " deactivation " effect to matrix, and there is significant roughening effect, can be formed micro-" anchor point " in a large number, thus be that combining closely between functional membrane bottom/matrix creates conditions.Prepare integrated technique as coating synthesis and coating, electrochemical cathode deposition there is non-linear, low temperature operability and controllability good, the advantage such as with low cost is one of desirable technique of material surface modifying.Cathode run can realize the fabricated in situ of matrix surface magnesium hydroxide, and heat treatment process can realize magnesium hydroxide to magnesian conversion and the sintering to existing rete.The formation of functional membrane bottom, internally for matrix one deck of putting on has protecting film from degradation characteristic, externally becomes the desirable substrate of follow-up coating (functional membrane surface layer) by means of its microstructure that is coarse, porous.When magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP independently use as coating material, there is the outstanding problems such as coating is difficult, adhesion is poor, and when it can be used as the disperse phase of the sandwich of layers of organic coating or macromolecular material based composites (wild phase) to use, the problems referred to above are then readily solved.Therefore, utilize technology provided by the invention, the optimized fabrication of controllable all-degradable biological material can be realized.

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 face layer section structure schematic diagram in embodiment;

In figure: 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 wherein two or more mixture layer, c-degradable high polymer material layer, d-is with magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or the wherein two or more mixture degradable high polymer material based composites layer that is wild phase.

Detailed description of the invention

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 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 up of melting, the large key step of shaping → anode polarization → cathodic deposition → heat treatment → coating five.The object of wherein melting, shaping is the article substrate that acquisition 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 " and " roughening " Duplex treatment to article substrate surface; The effect of cathodic deposition is to obtain magnesium hydroxide product layer, i.e. the prefilter layer of functional membrane bottom; Heat treated Main Function is to realize the sintering of cathodic deposition product to magnesian conversion and existing rete, obtains functional membrane bottom; The effect of coating is to carry out " reinforcement " from degradation function film bottom on the one hand, constructs functional membrane surface layer on the other hand.

As shown in Figure 2, be material section structure schematic diagram of the present invention.Controllable all-degradable biological material of the present invention, by pure magnesium or magnesium alloy substrate 1, covers matrix 1 surface and adjoin the functional membrane bottom 2 of matrix 1, and functional membrane surface layer 3 Integral construction adjoining functional membrane bottom 2 forms.

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, 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.Carry out melting respectively according to material composition, be shaped, obtain test specimen.Wherein melting condition: temperature 750-760 DEG C, 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), forging (magnesium alloy WE43) and hot extrusion (magnesium alloy AZ31), wherein permanent mold casting condition: 710-720 DEG C; Die Casting Condition: pouring temperature 660 DEG C, type temperature 220 DEG C, injection ratio pressure 50MPa, shot rate 40m/s; Forging condition: take cylindrical ingot as blank, open die forging, initial forging temperature 400 DEG C, final forging temperature 320 DEG C, forging ratio 1.87, the front 420 DEG C of insulation 2h of each forging; Hot extrusion condition: take cylindrical ingot as blank, extrusion temperature 350 DEG C, extrusion ratio 20, extruding rate 1.5m/min.The above-mentioned test specimen of Linear cut obtains the test sample being of a size of 20mm × 15mm × 2.5mm.By following specification, surface dressing is carried out to sample: alkali cleaning → washing → pickling → washing → silicon carbide paper polishing → washing → absolute ethyl alcohol successively from coarse to fine ultrasonic cleaning → hot blast drying → for subsequent use, wherein alkali cleaning condition: the combination solution of 40.0g/L NaOH, 10.0g/L sodium phosphate and 0.2g/L neopelex, 95 DEG C, 15min; Acid washing conditions: the combination solution of 20.0g/L nitric acid, 50.0g/L magnesium nitrate and 50.0g/L absolute ethyl alcohol, 25 DEG C, 15sec; Washing conditions: running water and distilled water rinsing successively.

Embodiment 1

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

Take carrene as solvent, preparation 40.0g/LPLLA solution, is labeled as S ₀₁; Take n-butanol as dispersant (liquid), add 10.0g/L magnesia (solid dispersed phase) and stir, obtained suspension, is labeled as S ₀₂; With the homogeneous mixture (mixed volume is than 2:1) of epoxychloropropane and acetone for solvent, first prepare 25.0g/LPLLA solution (liquid), then add 5.0g/L magnesia (solid dispersed phase) and stir, obtain suspension, be labeled as S ₀₃.By following specification, washing, dried heat treatment sample are carried out to 3 and take turns dip-coating processing: sample is immersed solution S ₀₁, take out after 7sec, after solidification to be coated, sample immersed suspension S ₀₂, take out after 15sec, after drying up with cold wind, sample immersed solution S ₀₁, take out after 3sec, sample is immersed solution S by solidification to be coated ₀₃, take out after 10sec, after spontaneous curing to be coated, sample immersed solution S ₀₁, take out after 7sec, solidification to be coated.Result obtains uniform composite coating (functional membrane surface layer) on heat treatment sample surface, and this coating is by 1) take magnesia as the PLLA coating of sandwich of layers, and 2) being sandwich of layers with magnesia/PLLA composite, PLLA coating is formed by stacking successively.

With SBF(simulated body fluid) be tested media (its composition and human plasma chemical composition contrast situation in table 1), control appearance face ratio (ratio that ie in solution volume is long-pending with specimen surface) 24ml/cm ², solution regeneration interval 24h, under probe temperature 37 DEG C of conditions, carrying out in vitro biodegradation respectively to said sample can test.Result shows: sample matrix after about 42d just starts to occur macroscopic erosion trace, compare the result namely starting 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 to corrode, 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 97d, shows that it has good in degradation characteristic; Sample is degradable after about 182d, shows that material monolithic has degradable characteristic.

Embodiment 2

With permanent mold casting state high purity magnesium sample for research object.Change into except 100.0g/L except by sodium chloride concentration, other condition of anode polarization controls with embodiment 1, found that: except single pit area increases, outside pit density and distributing homogeneity thereof reduce, and the other the same as in Example 1.Change into except 0.5g/L except by density of magnesium chloride, the control of other condition of cathodic deposition and result are with embodiment 1.Except temperature being changed into except 350 DEG C, the time changes into outside 24h, and the control of other condition of heat treatment and result are with embodiment 1.Take chloroform as solvent, first prepare 30.0g/LPLLA solution totally four parts, then add respectively 10.0g/L magnesium hydroxide, pure magnesium powder (spherical, median d ₅₀=47 μm), β-TCP and CPP, stir, obtain suspension, be labeled as solution S respectively ₀₄, S ₀₅, S ₀₆and S ₀₇.By following specification, washing, dried heat treatment sample are carried out to 2 and take turns dip-coating processing: sample is immersed solution S ₀₄in, take out after 15sec, after solidification to be coated, sample is immersed solution S ₀₅, take out after 15sec, after solidification to be coated, sample immersed solution S ₀₆, take out after 15sec, after solidification to be coated, sample immersed solution S ₀₇, solidification to be coated.Result obtains uniform composite coating (functional membrane surface layer) at specimen surface, and this coating is formed by stacking successively by the PLLA matrix composite coating being wild phase with magnesium hydroxide, pure magnesium, β-TCP and CPP respectively.Carry out the test of material bodies outside biodegradability with embodiment 1, result shows: sample matrix after about 39d 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 87d, shows that it has good in degradation characteristic; Sample is degradable after about 250d, shows that material monolithic has degradable characteristic.

Embodiment 3

With permanent mold casting state AZ31 magnesium alloy sample for research object.Change into except 20.0mg/L except by sodium chloride concentration, other condition of anode polarization controls with embodiment 1, found that: except pit density and the degree of depth reduce, treatment effect is with embodiment 1.Change into except 150.0g/L except by density of magnesium chloride, the control of other condition of cathodic deposition and result are with embodiment 1.Except temperature being changed into except 550 DEG C, the time changes into outside 1h, and the control of other condition of heat treatment and result are with embodiment 1.Take chloroform as solvent, preparation 75.0g/LPLLA solution, is labeled as solution S ₀₈; Take ethanol as dispersant (liquid), add 0.5g/L magnesium hydroxide (solid dispersed phase), stir acquisition suspension, is labeled as solution S ₀₉.Take carrene as solvent, first prepare 75.0g/LPLLA solution, then add 0.377g/L magnesia and stir, obtain suspension, be labeled as solution S ₁₀.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₀₈, take out after 7sec, after solidification to be coated, sample immersed solution S ₀₉, take out after 30sec, after drying to be coated, sample immersed solution S ₀₈, take out after 7sec, after solidification to be coated, sample immersed solution S ₁₀, take out after 20sec, solidification to be coated.Result obtains uniform by 1 at specimen surface) take magnesium hydroxide as the PLLA coating of sandwich of layers, and 2) composite coating (functional membrane surface layer) that is formed by stacking of magnesia/PLLA composite coating.Carry out the test of material bodies outside biodegradability with embodiment 1, result shows: sample matrix after about 21d 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 45d, shows that it has good in degradation characteristic; Sample is degradable after about 102d, shows that material monolithic has degradable characteristic.

Embodiment 4

With permanent mold casting state ZK60 magnesium alloy sample for research object.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.Except the concentration of PLLA is changed into except 0.2g/L, solution S ₀₈preparation with embodiment 3.Except the concentration of magnesium hydroxide is changed into except 45.0g/L, solution S ₀₉preparation with embodiment 3.Except changing the concentration of PLLA into 0.2g/L, magnesian concentration changes into outside 0.133g/L, solution S ₁₀preparation with embodiment 3.Carry out dip-coating processing with embodiment 3 to washing, dried heat treatment sample, result is with embodiment 3.Carry out the test of material bodies outside biodegradability with embodiment 1, 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 30d, shows that it has good in degradation characteristic; Sample is degradable after about 77d, shows that material monolithic has degradable characteristic.

Embodiment 5

With permanent mold casting state WE43 magnesium alloy sample for research object.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.Solution S ₀₁preparation with embodiment 1.Take acetone as dispersant (liquid), add respectively 10.0g/L magnesium hydroxide, pure magnesium powder (spherical, median d ₅₀=47 μm), β-TCP and CPP, stir, obtain suspension, be labeled as solution S respectively ₁₁, S ₁₂, S ₁₃and S ₁₄.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₀₁, take out after 10sec, after solidification to be coated, sample immersed solution S ₁₁, take out after 35sec, after drying to be coated, sample immersed solution S ₀₁, take out after 10sec, after solidification to be coated, sample immersed solution S ₁₂, take out after 35sec, after drying to be coated, sample immersed solution S ₀₁, take out after 10sec, after solidification to be coated, sample immersed solution S ₁₃, take out after 35sec, after drying to be coated, sample immersed solution S ₀₁, take out after 10sec, after solidification to be coated, sample immersed solution S ₁₄, take out after 35sec, after drying to be coated, sample immersed solution S ₀₁, take out after 10sec, solidification to be coated.The composite coating (functional membrane surface layer) that the PLLA coating that it is sandwich of layers with magnesium hydroxide, pure magnesium, β-TCP and CPP respectively that result obtains superposes successively.Carry out the test of material bodies outside biodegradability with embodiment 1, result shows: sample matrix after about 26d 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 50d, shows that it has good in degradation characteristic; Sample is degradable after about 125d, shows that material monolithic has degradable characteristic.

Embodiment 6

To forge state WE43 magnesium alloy sample for research object.Change into except 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 magnesium sulfate respectively except by the sodium chloride in electrolyte, the control of other condition of anode polarization and result are with embodiment 1.Change into except magnesium nitrate or magnesium sulfate respectively except by the magnesium chloride in electrolyte, the control of other condition of cathodic deposition and result are with embodiment 1.Heat-treat condition control and result are with embodiment 1.Solution S is carried out with embodiment 1 ₀₃preparation.With this solution to through washing, dried heat treatment sample brushes respectively, spin coating and spray treatment, acquisition surface density is 1.72mg/cm ²uniform magnesia/PLLA composite coating (functional membrane surface layer).Carry out the test of material bodies outside biodegradability with embodiment 1, result shows: sample matrix after about 44d 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 89d, shows that it has good in degradation characteristic; Sample is degradable after about 182d, shows that material monolithic has degradable characteristic.

Embodiment 7

With die casting state AZ31 magnesium alloy sample for research object.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.Solution S is carried out with embodiment 1 ₀₂preparation.PLLA solid particle is heated to complete molten condition and 210 DEG C of insulations, is labeled as solution S ₁₅.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₁₅, take out after 30sec, after solidification to be coated, sample immersed solution S ₀₂, take out after 15sec, after drying to be coated, sample immersed solution S ₁₅, take out after 2sec, solidification to be coated.Result is the PLLA coating (functional membrane surface layer) of sandwich of layers with magnesia in specimen surface acquisition uniformly.Carry out the test of material bodies outside biodegradability with embodiment 1, result shows: sample matrix after about 15d 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 27d, shows that it has good in degradation characteristic; Sample is degradable after about 130d, shows that material monolithic has degradable characteristic.

Embodiment 8

With As-extruded AZ31 magnesium alloy sample for research object.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.190.0gPLLA solid particle is heated to complete molten condition and 210 DEG C of insulations, adds the mixture of 5.0g magnesia and 5.0g magnesium hydroxide, after stirring, obtain suspension, be labeled as solution S ₁₆.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₁₆, take out after 45sec, after solidification to be coated, sample immersed solution S ₁₆, take out after 3sec, solidification to be coated.Result obtains the uniform PLLA matrix composite coating being wild phase with magnesia and magnesium hydroxide at specimen surface.Carry out the test of material bodies outside biodegradability with embodiment 1, result shows: sample matrix after about 23d 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 42d, shows that it has good in degradation characteristic; Sample is degradable after about 157d, shows that material monolithic has degradable characteristic.

Embodiment 9

With die casting state AZ91 magnesium alloy sample for research object.Anode polarization, cathodic deposition and heat-treat condition control and result are with embodiment 1.Solution S is carried out with embodiment 1 ₀₁, S ₀₂and S ₀₃preparation.By following specification, dip-coating processing is carried out to washing, dried heat treatment sample: sample is immersed solution S ₀₃, take out after 60sec, after solidification to be coated, sample immersed solution S ₀₂, take out after 15sec, after drying to be coated, sample immersed solution S ₀₃, take out after 20sec, after solidification to be coated, sample immersed solution S ₀₂, take out after 15sec, sample immersed solution S ₀₁, take out after 30sec, solidification to be coated.Result obtains composite coating (functional membrane surface layer) at cathodic deposition specimen surface, this coating is by 1) take magnesia as the magnesia/PLLA composite coating of sandwich of layers, 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.Carry out the test of material bodies outside biodegradability with embodiment 1, 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 140d, shows that material monolithic has degradable characteristic.

With further reference to BiologicalEvaluationofMedicalDevice ISO 10993 standard, with titanium alloy ti6al4v widely used on clinical medicine for negative control, carry out respectively testing with the biocompatibility that hemolysis rate and vitro cytotoxicity are representative to sample each in embodiment 1-embodiment 9, result shows: each sample all shows the good biocompatibility suitable with Ti6Al4V.

Table 1: tested media and human plasma chemical composition contrast

Claims (9)

1. a preparation method for bio-medical 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 article substrate;

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

C) cathodic deposition: it is in the group water solution of the magnesium chloride of 0.5-150.0g/L that the article substrate through step b) process is immersed concentration, and energising processes, obtains the prefilter layer having degraded protection and the functional membrane bottom from degradation characteristic concurrently;

D) heat treatment: the article substrate through step c) process is heat-treated, obtain and have degraded protection and the functional membrane bottom from degradation characteristic concurrently, wherein said heat treatment temperature is 350-550 DEG C, and temperature retention time is 1-24h;

E) apply: comprise following key step:

E-1) preparation of solution:

1# solution: for PLLA(gathers left lactic acid), 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 magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP(bata-tricalcium phosphate), CPP calcium polyphosphate or wherein two or more mixture for solid dispersed phase, with water, acetone, ethanol, n-butanol or the wherein two or more mixture suspension that is 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 mixture for solid dispersed phase, with the suspension that the organic solvent based sols of PLLA, PLGA or its mixture 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;

E-2) coating of coating: carry out coating processing to the article substrate through step d) process, obtains and has degraded protection and the functional membrane surface layer from degradation characteristic concurrently, and more than one in the following three kinds of schemes of described coating processing employing carry out:

Scheme one: conbined usage e-1) step joins 1# solution and 2# solution, and follow first by the order using 1# solution after 1# solution with 2# solution again, carry out taking turns above coating;

Scheme two: independently use e-1) step joins 3# solution and carries out taking turns above coating;

Scheme three: conbined usage e-1) step joins 1# solution, 2# solution and 3# solution, and follow first by the order using 3# solution after 1# solution with 2# solution again, carry out taking turns above coating.

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

3. the preparation method of bio-medical material according to claim 1, it is characterized in that: step e-1) described in the organic solvent of 1# solution and 3# solution be one in A solvent and B solvent, wherein A solvent is more than one in epoxychloropropane, carrene or chloroform, and B solvent is the mixture obtained after more than one Homogeneous phase mixing in A solvent and acetone, ethanol or n-butanol; Step e-1) described in pure Magnesium and magnesium alloys in 2# solution and 3# solution be Powdered, graininess, sheet, thread, banded, tubulose or crystal whisker-shaped, and its OCP in any equivalent environment medium not higher than article substrate in the OCP of pure magnesium or magnesium alloy.

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

6. the preparation method of bio-medical material according to claim 1, is characterized in that: after coating is containing the coating of PLLA or PLGA, carries out spontaneous curing or manually solidify process, until this coating layer portion or after solidifying completely, then carries out the coating of follow-up coating; As coating magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or wherein after two or more mixture, carry out drying and process.

7. the bio-medical material obtained by preparation method according to claim 1, what it is characterized in that comprising pure magnesium or magnesium alloy substrate and cover matrix surface has degraded protection and the functional membrane from degradation characteristic concurrently, and wherein functional membrane comprises bottom and surface layer; Described bottom forms primarily of the mixture of magnesia or magnesia and magnesium hydroxide; Described surface layer comprises at least one in No.1 coating and No.2 coating; Described No.1 coating is with magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or the wherein two or more mixture degradable high polymer material layer that is sandwich of layers; Described No.2 coating is that the quality of wherein said wild phase accounts for the 0.5%-40% of composite quality with magnesia, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or the wherein two or more mixture degradable high polymer material based composites layer that is wild phase; Degradable high polymer material in described No.1 coating and No.2 coating is PLLA, PLGA or its mixture.

8. bio-medical material according to claim 7, 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; In described No.1 coating, the composition of the degradable high polymer material layer of sandwich of layers both sides, structure and thickness are identical or different; Sandwich of layers No.2 coating in described No.1 coating replaces; In described No.1 coating, at least one deck No.2 coating of the degradable high polymer material layer of sandwich of layers both sides replaces.

9. bio-medical 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, sheet, 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.